PMID- 1403480 TI - An investigation of internal phase losses during the microencapsulation of fragrances. AB - Prototype fragrances, prepared from common fragrance components, were extracted with water, recovered, and characterized by gas chromatography before and after the water treatment, revealing a significant loss of the more water-soluble components. Unextracted prototype fragrances were also microencapsulated by a gelatin/gum arabic coacervation process. The microencapsulated fragrance oils were recovered from the microcapsules, using pepsin enzyme to open up the capsules. Comparison of GC results of microencapsulated fragrance oil versus unencapsulated oil showed many of the changes could be ascribed to solubility losses of the more water-soluble components to the process water. Deliberate inclusion of toluene as a fragrance component in one of the prototype fragrances showed that some losses of highly volatile fragrance components can be expected during microencapsulation; but because most fragrance components do not approach the volatility of toluene, such losses are expected to be minimal. Chromatograms taken before and after microencapsulation of two commercial fragrances are discussed. PMID- 1403481 TI - Drug encapsulation in alginate microspheres by emulsification. AB - A method based on an emulsification process was developed for the production of calcium alginate microspheres. Isopropyl alcohol and acetone, which are strong dehydrating agents, were used to aid in the hardening and drying of the microspheres. However, the amount of drug encapsulated was very low. This was due to the drug being soluble in the dehydrating solvents. In the absence of the solvents a high percentage of drug was encapsulated, and this was further increased by forming the microspheres by phase inversion. It was also found that a suspension of the drug particles was required for effective microencapsulation. The efficiency of drug encapsulation generally increased with the ratio of drug to encapsulating material. The microspheres produced were free-flowing and most of them were smaller than 150 microns. PMID- 1403482 TI - In vitro stability of liposomes in the presence of polymers, trehalose and sodium taurocholate. AB - We report the influence of synthetic polymers, trehalose and sodium taurocholate on the stability of both MLVs* and SPLVs prepared from a range of lipids including synthetic polyhydroxyl lipids. In the absence of cryoprotective agents liposomes were found to release greater than 90 per cent of encapsulated marker when exposed to freeze-thawing or freeze-drying procedures. In the presence of polyvinylpalmitate a marginal enhancement of stability towards freeze-drying was observed, the effect being most marked with cholesterol-containing liposomes. Trehalose was also found to stabilize all preparations investigated towards freeze-drying. In particular SPLVS prepared from (C18:0, C14:0-GMG):EPC:C retained in greater than 90 per cent of the entrapped marker. Addition of polymers to trehalose-containing SPLVS did not further increase the stability. SPLVS prepared from lipids possessing a high transition temperature demonstrated enhanced stability in the presence of bile salts. This effect was most marked with SPLVs prepared from (C18:0, C22:0-GMG):C. PMID- 1403483 TI - Dependence on pH of permeability towards electrolyte ions of poly(L-lysine-alt terephthalic acid) microcapsule membranes. AB - Permeation of electrolyte ions through poly(L-lysine-alt-terephthalic acid) microcapsule membranes was studied as a function of the pH of the medium at different ionic strengths. When the pH of the medium was varied, the permeation rate for 5-sulphosalicylate anions, as well as phenyltrimethylammonium cations, was slow at pH values lower than 4, showed a sudden and large increase in the pH range between 4 and 6, and thereafter remained unchanged. This remarkable change in the permeation rate was found to be produced by an abrupt increase in the microcapsule size observed in the same pH range. Increase in the ionic strength of the medium at pH values higher than 6 increased the rate of anion permeation but decreased the rate of cation permeation due to increase in the screening effect of salt ions on the negative charges in the microcapsule membranes. PMID- 1403484 TI - In vivo distribution and antitumour activity of liposomal 3',5'-O-dipalmitoyl-5 fluoro-2'-deoxyuridine. AB - 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine (FUdR-dipalmitate), a lipophilic prodrug of 5-fluoro-2'-deoxyuridine (FUdR), was incorporated in different types of liposomes. The in vivo distribution and intrahepatic deacylation of liposomal FUdR-dipalmitate was found to be strongly dependent on liposome composition and on drug to lipid ratio. The use of fluid-type liposomes (egg PC/PS/CHOL) rendered FUdR-dipalmitate more susceptible to enzymatic breakdown than solid-type liposomes (DSPC/DPPG/CHOL). A decrease of the retention of the drug in the body was also obtained when FUdR-dipalmitate was incorporated in solid-type liposomes with high drug to lipid ratio (1:10) than with low ratio (1:50). In spite of these substantial differences in the rates at which FUdR was liberated from liposomes with different fluidity, size, or drug to lipid ratio, only minor differences in therapeutic effect were observed in a number of murine tumour models (P388 leukaemia, Lewis Lung carcinoma, B16 melanoma and a C26 adenocarcinoma liver metastasis model). The lipophilic prodrug of FUdR exhibited antitumour activity at 100-600 times lower doses than the free drug. However, at these therapeutic doses FUdR-dipalmitate was also far more toxic. This prohibited the use of higher doses to increase antitumour activity. PMID- 1403485 TI - Polymeric pseudolatices bearing pilocarpine for controlled ocular delivery. AB - The pseudolatex-based ocular formulations of pilocarpine were prepared using different combinations of Eudragit RS 100 and polyvinyl pyrrolidone for prolonged and controlled release of the drug. The designed system was essentially based on polymeric pseudolatex dispersion. The process variables that effect the latex particle size, drug loading and release profiles of drug were studied. Preparations were evaluated for their in vitro performance with regard to release profile and diffusion co-efficient. The designed system exhibited linear relationship between cumulative drug release (Q) and square root of time (t0.5). The products selected on the basis of in vitro characterization were studied for in vivo performance evaluation. It was observed that the preparations exhibited in vivo prolonged therapeutic efficacy. Thus polymer based pseudolatices hold promise for controlled pilocarpine ocular delivery. PMID- 1403486 TI - Erythrocyte based delivery system of primaquine: in vitro characterization. AB - Primaquine phosphate, an antimalarial drug, was loaded in erythrocytes by the process of endocytosis. The encapsulation of 0.1-0.15 mg of drug ml-1 of packed erythrocytes was achieved. The loaded cells attained spherical shape and exhibited higher osmotic fragility and lower resistance to turbulence shock as compared with normal cells. Glutaraldehyde treatment stabilized the cells which were noted to be resistant to the osmotic and turbulence shocks. In vitro release of drug and haemoglobin was also retarded upon treatment of loaded erythrocytes with glutaraldehyde. The studies suggest the potentiality of primaquine-loaded, glutaraldehyde-treated erythrocytes as an intravenous drug delivery system for casual prophylaxis and radical cure of malaria. PMID- 1403487 TI - Preparation and in vitro evaluation of slow release ketoprofen microcapsules formulated into tablets and capsules. AB - Ketoprofen powder was encapsulated with Eudragit RL/RS polymer solutions in isopropanol-acetone 1:1, using a simple and rapid method. Microcapsules were prepared using Eudragit solutions with different RL/RS ratios. The encapsulation process produces free-flowing microcapsules with good drug content and marked decrease in dissolution rate. The retardation in release profile of ketoprofen from microcapsules was a function of the polymer ratio employed in the encapsulation process. In vitro release of ketoprofen from microcapsules either filled in gelatin capsules or compressed into tablets, using calcium sulphate as diluent, confirmed the efficiency of the encapsulation process for preparing prolonged release medication. A capsule formulation with optimum sustained release profile was suggested. PMID- 1403488 TI - Preparation and physical evaluation of microcapsules of hydrophilic drug cyclodextrin complexes. AB - An emulsion-solvent evaporation method for preparation of microcapsules containing water-soluble 2-hydroxypropyl-beta-cyclodextrin complex of a lipophilic water-insoluble drug, hydrocortisone, is described. The release of the drug from the microcapsules was determined in simulated gastric fluid. The drug release rate from the microcapsules could be controlled by addition of a plasticizer and it was sustained over extended time. Addition of solubilizing compounds to the dissolution medium did not affect the drug release rate. PMID- 1403489 TI - Release kinetics of fluphenazine from biodegradable microspheres. AB - Fluphenazine-loaded microspheres were prepared using biodegradable lactide and lactide-co-glycolide polymers. Sustained release of fluphenazine was achieved with fluphenazine loadings of up to 30 per cent in both the lactide and lactide co-glycolide polymers. Fluphenazine release from microspheres was found to increase with increasing drug loading and was most rapid from the poly-L-lactide co-glycolide microspheres. The release profiles showed a 'lag' period followed by an accelerating release phase and in some cases a decay period, i.e. the release profiles were sigmoidal and fitted the Prout-Tomkins equation (Prout and Tompkins 1944). Consequently it was considered that polymer degradation, the primary rate determining step controlling drug release, occurred by a mechanism involving propagation of active sites, drug release reflecting the spread of this degradation throughout the polymer. PMID- 1403490 TI - Preparation and evaluation of abietic acid microcapsules by a solvent evaporation technique. AB - Abietic acid was isolated from rosin N Grade (ISI) by a simple process and the product was further standardized. Sulphadiazine microcapsules were prepared by the solvent evaporation technique, using abietic acid as a wall-forming material. Discrete, spherical and free-flowing microcapsules were obtained by phase separation induced by solvent evaporation using bentonite as a solid emulsifier. The prepared microcapsules were evaluated for drug content, wall thickness, flow properties, size distribution, density and in vitro dissolution studies in gastric fluid. The effect of various process variables such as agitation speed, coat-core ratio, etc., on the micromeritic and release characteristics has been described. PMID- 1403491 TI - Poly(4-vinylpyridine)-coated liposomes: stability studies and release of acetylsalicylic acid. AB - Liposomes of dimyristoylphosphatidylcholine (DMPC) and dicetylphosphate (DCP) reacted with 4-vinylpyridine (4-VP) to form a salt and, subsequently, autopolymerized for form poly(4-vinylpyridine) (poly(4-VP))-coated liposomes. The conditions for optimization of polymer coating have been determined; also, the effects of polymer coating on liposome stability, the encapsulation of ASA and its release kinetics have been measured. The coating efficiency was maximum at a DMPC:DCP 1:1 mole ratio, at pH 4.0 in acetate buffer, and a polymerization time of 40 min. The polymer-coated liposomes were stable in 2 mM sodium cholate and 4 per cent isopropanol solutions, as determined from turbidity measurements, versus a 20-25% decrease in stability of uncoated liposomes. The encapsulation efficiency of ASA reached a maximum of 9 per cent at DMPC:DCP 1:1 mole ratio. The release of ASA at 37 degrees C, pH 7.0 was characterized by an initial fast release (85 and 63 per cent in 20 min from uncoated and polymer-coated liposomes, respectively) followed by a slow, constant release rate up to 140 min. Thus, autopolymerization of a polymerizable monomer at liposome surfaces represents a potentially feasible stabilization approach for liposomes exposed to sodium cholate solutions with greater retention of solute than uncoated liposomes. PMID- 1403492 TI - Release kinetics of salbutamol sulphate from wax coated microcapsules and tableted microcapsules. AB - Microcapsules of salbutamol sulphate were prepared using beeswax and carnauba wax as coating materials. In vitro release kinetics were studied following the zero order, first order and Higuchi equations. Beeswax alone was not effective but beeswax and carnauba wax combinations were suitable in controlling the in vitro release of the drug. Microcapsules were compressed into tablets to get a controlled release oral dosage form. Release from tableted microcapsules was significantly more prolonged than the respective batches of the microcapsules. Best data fit with the highest correlation coefficient for the tableted microcapsules was obtained for first order. PMID- 1403493 TI - Bioadhesive polymer-grafted starch microspheres bearing isosorbide dinitrate for buccal administration. AB - A polymer-grafted mucoadhesive system bearing isosorbide dinitrate was prepared for buccal administration. Polymer grafting of starch microspheres modified drug release and surface characteristics of microspheres. Bioadhesion and factors affecting bioadhesion were studied. Process variables that could affect microsphere size, and as a result the release of the drug, were also studied. It was observed that compression of grafted starch microspheres modified drug release and extended drug action via slow release following buccal application. Prepared system(s) were characterized for drug release and in vivo performance and compared with conventional oral treatment. The systems were noted to be promising. PMID- 1403494 TI - Improvement of a microencapsulation with aqueous core by factorial design. AB - Preparation of microcapsules with aqueous core and polyamide walls is influenced by several factors. We improved the stability of walls and size of capsules by simultaneous variation of four factors: total ratio of polymer, ratio of amines to acid chlorides, concentration of surfactant and speed of stirring. Use of factorial design minimizes the number of experiments and permits us to know the influence of these factors and of their interactions. By increasing the ratio of amines to acid chlorides and with a low concentration of total polymer, we obtained more stable capsules. Surfactant had a negative effect on the hardness of the polymer. PMID- 1403495 TI - Polyacrylate resin microcapsules for taste masking of antibiotics. AB - Various microencapsulated dosage forms were prepared to limit the release of an antibiotic in solution for up to 3 days and in the oral cavity following per oral administration. An experimental antibiotic, clarithromycin (TE-031), was used in these studies. The drug was first encapsulated in gelatin followed in some cases by crosslinking with glutaraldehyde. The gelatin microcapsules were then coated with acrylic resins (Eudragit), whose solubility properties vary according to pH. A non-solvent coacervation technique was used to apply the Eudragit resins. It was found that crosslinking the gelatin retarded release of TE-031 somewhat relative to that from uncrosslinked gelatin microcapsules in a 72h release experiment conducted at room temperature. Coating the gelatin microcapsules with Eudragit resins L100, S100, or E100 slowed the release of TE-031 further still; less TE-031 was released over 72 h from the Eudragit-coated formulations prepared with crosslinked gelatin compared with formulations prepared with uncrosslinked gelatin. The Eudragit E100-coated crosslinked gelatin microcapsule formulation was most effective in preventing release of the TE-031 under simulated conditions of storage in an aqueous solution. PMID- 1403496 TI - Microencapsulation of terbutaline sulphate by the solvent evaporation technique. AB - Terbutaline sulphate microcapsules were prepared by coacervation-phase separation (solvent evaporation) technique using ethyl cellulose as a coating material. Acetone, ethyl alcohol and isopropyl alcohol were employed as solvents for coating material. Microcapsules were evaluated for their drug content, particle size distribution (microscopic method), flow properties, bulk density, in vitro dissolution, drug release kinetics and surface characteristics (scanning electron microscopy). PMID- 1403497 TI - Peritoneal exudates from microencapsulated rat islets of Langerhans xenografted mice presenting characteristics of potentially cytotoxic non-specific inflammation. AB - Grafted polyacrylamide microencapsulated islets of Langerhans in the peritoneal cavity of mice did not survive more than a few days, perhaps owing to a non specific inflammatory reaction or an immune rejection. To assess the two hypotheses, we used flow cytometry (FACS) to analyse cell populations of empty or islet-loaded microcapsules grafted in the peritoneal cavity of mice, and performed cytotoxic assays with proteases secreted by inflammatory cells. An immune rejection did not seem to occur, but the degree of inflammation could explain the short life of the grafts. PMID- 1403498 TI - Pseudomembranous colitis following resection for Hirschsprung's disease. AB - Enterocolitis is the most common cause of significant morbidity and death in Hirschsprung's disease. Although most cases respond to nasogastric decompression, antibiotics, and colonic evacuation, some children have an unusually fulminant or protracted clinical course. Four cases are reported of pseudomembranous colitis (PMC) that developed 1 to 18 months (mean, 8 months) after definitive surgery for Hirschsprung's disease (Soave endorectal pull-though, 2; Duhamel procedure, 2). While all children presented with fever, abdominal distention, and diarrhea, indistinguishable from typical Hirschsprung's enterocolitis, the clinical course was fulminant in two cases, both of whom died of septic shock. Postmortem examination in both showed extensive colonic pseudomembranes despite identification of Clostridium difficile toxin and subsequent vancomycin therapy (initiated late in the clinical course). Two children in the series had protracted hospitalizations and eventually required diverting enterostomy despite recognition of C difficile toxin and treatment with enteral vancomycin, in one child necessitating multiple courses of antibiotic therapy. Awareness of the virulence of PMC associated with Hirschsprung's disease (even after definitive resection) should prompt submission of stool specimens from any child who presents with enterocolitis for both C difficile culture and toxin levels. On the basis of our experience it is our policy to initiate a prompt course of vancomycin by rectal lavage or nasogastric tube in all children with Hirschsprung's enterocolitis, pending culture results, in view of the significant morbidity and mortality exemplified by cases in this review. PMID- 1403499 TI - Sirenomelia: case of the surviving mermaid. AB - This report describes a neonate with sirenomelia who was recently treated at British Columbia Children's Hospital. Prenatal diagnosis was made at 29 weeks' gestation. Survival was not anticipated. Cesarean-section at term showed a live 2,375-g infant with excellent Apgar scores. Anomalies noted were fused lower extremities, imperforate anus, colon atresia, bilateral fused pelvic kidneys with renal dysplasia, pelvic and sacral dysplasia, and genital abnormalities. Laparotomy and colostomy were performed. All other anomalies are compatible with life and she is neurologically normal. Eventual separation of the lower extremities is planned. This is the second reported case of survival in a patient born with sirenomelia. PMID- 1403500 TI - The bowel management tube: an effective means for controlling fecal incontinence. AB - Regular bowel washout enemas have been used as a method of management of fecal incontinence. The effective administration of a washout enema to a child with weak anal sphincters is often a problem. Using a new silastic balloon-tipped enema catheter (bowel management tube [BMT]) of our design, we prospectively studied its effectiveness in a group of children who suffered fecal incontinence. Thirty-one children were studied over a 1-year period. Their diagnoses included meningomyelocele (19), postoperative Hirschsprung's disease or imperforate anus (10), and other (2). Before and after starting the BMT enema system, clinical assessment and a diary, which graded the degree of fecal incontinence and satisfaction with the system, were completed. Five patients failed to benefit because of noncompliance (3) or balloon extrusion (2). Three more patients discontinued the use of the tube system. Twenty-three patients achieved successful results with this system as evidenced by a significant amelioration in their fecal incontinence and their unwillingness to give up the use of the BMT. We conclude that the use of a regular washout enemas with BMT can be an effective method for control of fecal incontinence in children. PMID- 1403501 TI - Motility and sensation of the rectosigmoid and the rectum in patients with anorectal malformations. AB - Motility of the rectosigmoid and rectum and reservoir function of the rectum after surgery for anorectal malformations were investigated in 32 patients (17 with high type, 6 with intermediate type, and 9 with low type anomaly) aged 5 to 16 years. All 32 patients were examined manometrically as well as with a newly devised myoelectrical method. Manometry showed that the values of maximum anal pressure and anorectal pressure difference in the high type were significantly lower than those in the low type. However, the incidence of contractile activity of the rectosigmoid was not significantly different between these two groups. The threshold sensation pressure and the maximum tolerable pressure in the high type were significantly higher than those in the low type, and the rectal compliance in the high type was significantly lower than that in the low type. Electromyography was recorded at 8 cm and 5 cm from the anal verge. Two types of slow waves were observed, a faster rhythm and a slower rhythm. Their frequency was similar in the three groups. However, the numbers of spike bursts in the high type and intermediate type were significantly higher than those in the low type. These results indicate that in addition to an inadequate anal resting pressure a loss of optimal rectal sensation or rectal reservoir function might be associated with fecal incontinence in the high type and that increased spike bursts might play some role in rectal motility. PMID- 1403502 TI - Congenital urethral fistula with normal anus: a report of two cases. AB - Congenital rectourethral or anourethral fistulae without imperforate anus in males are rare, representing less than 1% of anorectal malformations. We report our experience with two males with "N type" urethral fistulae. One, a 5-year-old boy, presented with recurrent urinary tract infections (UTIs) and passage of urine per anus. Investigations included a voiding cystourethrogram (VCUG), which demonstrated a fistula from the urethra to the anus. On physical examination, a small perianal opening was noted just outside the anus, which drained a small amount of urine after voiding. The fistula was excised via a perineal approach. The second patient is a 5-year-old boy with a long history of recurrent UTI requiring multiple hospitalizations since the newborn period. Chronic renal failure developed as a complication of repeated urinary tract infections. Investigations showed a single hydronephrotic pelvic kidney and a small bladder. He underwent numerous diagnostic and reconstructive procedures including cystoscopy and augmentation cystoplasty. Recurrent infections continued and an N type anourethral fistula was eventually diagnosed. The fistula was located between the anal canal and the membranous urethra. An anterior perineal approach was also used. Both fistulae were easily located, and reconstructive surgery of the urethra was not required. Postoperative VCUGs in both patients were normal. They have been free of infection with normal urinary continence since resection of the fistula. Congenital N type anourethral fistulae are rare, but should be considered in cases of recurrent urinary tract infections. The diagnosis may be missed by endoscopic procedures, but VCUG should demonstrate the fistulous tract. PMID- 1403503 TI - Blunt traumatic disruption of the thoracic aorta: a rare injury in children. AB - Rupture of the thoracic aorta secondary to blunt chest trauma is an exceedingly uncommon injury in pediatric patients. We present a case of blunt traumatic aortic disruption in a 10-year-old child who was successfully managed by primary aortic repair using partial cardiopulmonary bypass. The epidemiology and pathophysiology of this injury, with particular reference to children, is reviewed. The ongoing controversies regarding the diagnosis and operative management of this injury are summarized. PMID- 1403504 TI - Adult-to-neonate lung transplantation: anatomic considerations. AB - Babies born with severe pulmonary hypoplasia are unsalvageable despite maximal therapy including extracorporeal membrane oxygenation (ECMO). Using ECMO as a bridge to transplantation, reduced-size lung grafts (pulmonary lobe or segment) could expand the pool of cadaver donors and may allow for HLA-matched living related transplants. We tested this concept first in the piglet model and developed the technical maneuvers necessary to perform lobar and segmental lung transplants from adult pigs into neonatal piglets. Prior to clinical application, a systematic evaluation of anatomic considerations for reduced-size human lung transplantation was needed. A series of human adult and neonatal cadaver thoracic dissections were performed to determine the adult pulmonary lobe or segment with the proper size, orientation, and vascular and bronchial anatomy for use as a neonatal lung transplant. The adult right middle lobe (RML) is the best candidate for neonatal left lung replacement. The adult RML, once removed, can be rotated 180 degrees around its superior-inferior axis and the vessels and bronchus align well in the left chest of the neonate. The RML may require further reduction to fit into the neonatal left chest. Selective arterial perfusion of the RML showed the anterior segment to be a near-perfect match for fit and anatomy. This technique may eventually permit living-related lung transplantation. PMID- 1403505 TI - Juvenile hemangiomas involving the thoracic trachea in children: report of two cases. AB - Two 3-month-old girls presented with posterior mediastinal juvenile hemangioma (JH), a benign tumor rarely found in the mediastinum. Incomplete resections were performed. Over 4 and 7 months, respectively, the hemangiomas recurred and grew through the tracheal wall into the tracheal lumina, reducing the airway by 90% in one case and 70% in the other. The recurrences were resected, including five tracheal rings in the first case and four in the second. In case 1 the tumor recurred in the trachea 2 months later. A tracheostomy was performed, and corticosteroids were administered for 6 months. The tumor involuted and the patient was decannulated after 18 months; she is doing well 7 years later. The patient in case 2 has been well in the 18 months since her second operation. Airway obstructions can be treated by tracheal resection when conservative management fails. PMID- 1403506 TI - Rigid bronchoscopy in the pediatric age group: diagnostic effectiveness. AB - Over a 15-year period, 277 diagnostic bronchoscopic procedures were carried out at the Winnipeg Children's Hospital using rigid bronchoscopic instrumentation. The objective of the review is to examine contribution to final diagnosis made by the procedure. The patient population included 60% male and 40% female patients ranging from the first day of life to 18 years (mean age, 6 years). Indications for bronchoscopy fell into two large groups, including 60% of patients with evidence of lower airway disease and 30% of patients with evidence of upper airway obstruction. In patients with upper airway obstruction, half were found to have a congenital underlying cause and half were due to an acquired lesion. In 85% of patients, a specific diagnosis was reached and this proved to correlate positively with the preoperative diagnosis in 80% of patients and negatively in 20%. Definitive treatment in patients with upper airway obstruction included surgical intervention in one third of patients. Patients with lower airway disease were diagnosed as having consolidation in 43%, atelectasis in 39%, and bronchiectasis in 18%. Disease localized most frequently to the left lower and right upper lobes and in only 10 of 168 patients was a congenital cause determined. Among 168 patients, 30 had surgical treatment as the definitive management with the majority of patients treated medically. Bronchoscopy was shown to contribute to diagnosis in 88% of patients examined. Bronchoscopy was carried out with a complication rate of 3% and no mortality. PMID- 1403507 TI - The use of indium 111 leukocyte scans in children with inflammatory bowel disease. AB - Indium 111 leukocyte (WBC) scans have been used in the investigation of inflammatory bowel disease in recent years, but their use in children is not well described. We reviewed our experience with 281 indium 111 scans over an 8-year period in a total of 109 children with inflammatory bowel disease (Crohn's disease 70, ulcerative colitis 39). One hundred twenty-eight indium 111 scans done within 2 weeks of a radiographic contrast study, endoscopic examination, or surgical procedure were evaluated for diagnostic accuracy. Analysis showed that indium 111 scans were accurate when compared with conventional diagnostic tests and operative findings. This noninvasive imaging technique can play a useful role in the management of children with inflammatory bowel disease. PMID- 1403508 TI - Diaphragm of the gallbladder: a case report. AB - Gallbladder anomalies are rare and normally affect its shape, size, and position. We report on a 3-year-old boy with a gallbladder divided transversally by a windsock-type diaphragm, isolating the fundus from the rest of the biliary tree. Bilobed and multiseptated gallbladder have been described before, but this is the first isolated case of a congenital hourglass gallbladder. PMID- 1403509 TI - Agenesis of the gallbladder in duodenal atresia: two case reports. AB - Agenesis of the gallbladder not associated with biliary atresia is quite rare. We wish to report two patients with gallbladder agenesis in association with duodenal atresia without biliary atresia. Liver biopsy in one patient was notable for an absence of both inflammation and ductal pathology. The unremarkable postoperative course included normal direct bilirubins and a HIDA scan that demonstrated very good bile excretion into the duodenum. Both children are doing quite well in follow-up. PMID- 1403510 TI - Cholelithiasis in newborns and infants. AB - Cholelithiasis in infants is rare, and has usually been associated with hemolysis, ileal disease, congenital anomalies of the biliary tree, hyperalimentation, and prolonged fasting. With the increased use of abdominal ultrasonography (US), more cases of cholelithiasis are being discovered. We report our experience with 13 infants diagnosed on abdominal US to have gallstones. There were 9 boys and 4 girls with an average age at diagnosis of 2.6 months (range, 0 to 9 months). Predisposing factors could be identified in only 6 of the 13 patients. Two patients with obstructive jaundice underwent cholecystectomy and common bile duct exploration. One patient with choledocolithiasis and common bile duct dilatation was observed. His stone passed spontaneously, with resolution of symptoms. Ten patients without cholestasis remained asymptomatic, with disappearance of lithiasis in five of them. Neonatal cholelithiasis is more common than previously suspected; it seems to affect males more often than females and is usually not associated with known predisposing factors. It appears to be a temporary, self-limiting phenomenon, and an aggressive approach is not warranted in the asymptomatic infant. Surgical or radiological intervention should be reserved for the symptomatic patients or those with underlying lithogenic disorders. PMID- 1403511 TI - Coagulopathy associated with large sacrococcygeal teratomas. AB - Twelve neonates with sacrococcygeal teratoma (SCT) have been treated at British Columbia Children's Hospital over the past 5 years. Clinically significant coagulopathy developed in four of these neonates and two died, one before surgical intervention could be undertaken. Disseminated intravascular coagulation (DIC) was found in one patient and thrombocytopenia in another on preoperative laboratory studies. Etiology of the coagulopathy is unclear, but appears to be multifactorial. Although several clinical reviews have noted mortalities due to exsanguinating hemorrhage, no study has focused solely on this issue. The diagnosis of SCT in the neonate at high risk for development of coagulopathy is usually made prenatally. Premature labor is often precipitated by associated polyhydramnios and large tumor size. Fetal distress, prematurity, and low birth weight are common. Presence of placentamegaly, hydrops fetalis, and congestive heart failure are ominous prognostic signs. Early identification of patients at increased risk for development of hemorrhagic complications may allow optimization of their management. Cesarean section should minimize trauma to the SCT during delivery. Expeditious resection of the lesion may improve survival. PMID- 1403512 TI - Cystic neuroblastoma. AB - In the newborn, cystic masses of the adrenal gland are unusual findings and most are secondary to hemorrhage. We present a patient with a clinical history typical for adrenal hemorrhage who was found to have a thick walled cystic adrenal mass on both physical and ultrasound examination. During evaluation the mass decreased in size, but vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were elevated. Laparotomy and left adrenalectomy confirmed the diagnosis of a cystic neuroblastoma. Adrenal cyst, adrenal abscess, and cystic neuroblastoma are all rare entities in the newborn. We recommend that all cystic masses of the adrenal be evaluated by urinary VMA and HVA and that the possibility of cystic neuroblastoma be kept in mind when an adrenal cystic mass is followed nonoperatively. PMID- 1403513 TI - Inguinal hernias in very low birth weight infants: incidence and timing of repair. AB - Although the increased occurrence of inguinal hernias (IH) in premature children is well known, its incidence in the very low birth weight (VLBW, < 1,500 g) subpopulation has not been previously established. Additionally, because of associated problems, these children present the surgeon with a dilemma in regards to the most appropriate time for repair. We sought to determine the incidence of IH, rate of incarceration, perioperative problems, and to possibly define the ideal time for correction. Between 1977 and 1987, 1,933 children under 1,500 g birth weight were admitted to our neonatal intensive care unit. Of these, 1,391 lived for at least 28 days and were followed until 20 months corrected age. IH was diagnosed in 222 of 1,391 (16%) of those who survived 28 days or more. IH occurred in 174 of 670 (26%) of the boys and 48 of 721 (7%) of the girls. The incidence by side was right 19.8%, left 14.9%, bilateral 61.7%, and was unclear 3.6%. Of the 222 infants with IH, 192 were operated at our institution at a mean postnatal age of 28 weeks (range, 5 to 110 weeks). Of these, 35 were operated prior to neonatal discharge. One or more incarcerations occurred in 35 VLBW operated at this hospital. In only one infant, an emergency operation was needed because of irreducibility. There was no operative mortality and minimal morbidity. Five recurrences occurred during the 20 months' follow-up. This series establishes the incidence of IH in VLBW (during the first 20 months). The wide range in age at operation suggests that no single criterion can be established for ideal timing of repair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403514 TI - The nutrition of the fetus with intestinal atresia: studies in the chick embryo model. AB - This article examines the effects of experimental prenatal intestinal obstruction on the growth and blood composition of chick embryos. Intestinal atresia (IA) was produced by bipolar bowel electrocoagulation in fertile eggs on the 14th day of incubation. The chicks killed on the 19th day were measured, weighed, and blood sampled. Twenty-three control, 10 sham-operated, and 11 IA chicks were studied. Animals with IA were severely undernourished by weight (43.4 +/- 4.7 v 70.3 +/- 7.6% of egg weight, P < .001) and length (15.3 +/- 1.1 v 18.1 +/- 0.9 mm tibial length, P < .001) in comparison with sham-operated ones. Their hematocrit was slightly lower, and total protein increased. Prealbumin was absent in their sera and albumin, alpha and beta globulins were significantly decreased, whereas gamma globulin was greatly increased. Sodium, potassium chloride, urea, and glucose remained within normal limits. The lack of placenta in the avian embryo precludes any supply of nutrients by this route and the ingestion of amniotic fluid, which is protein-rich after the 13th day of incubation, when the opening of the seroamniotic connection allows albumen to be mixed with it, becomes the main source of nutrients until hatching. Obstruction of the main incoming avenue by IA induces severe malnutrition in this model which relies on this route to a greater extent than the human fetus. In spite of the obvious biological differences between the avian embryo and the human fetus, the present evidence supports the hypothesis that prenatal interruption of the amniotic fluid transit contributes to fetal undergrowth in IA. PMID- 1403515 TI - New techniques in fetal surgery. AB - Optimal fetal management during and after fetal surgery has been limited by an inability to reliably monitor the fetal heart rate and temperature, and by a lack of access to the fetal circulation. In order to solve these problems, we used early third trimester fetal sheep to develop: (1) an implantable radiotelemetry device that transmits the fetal electrocardiogram and temperature, and (2) an intraosseous access technique. A miniaturized radiotelemeter was implanted subcutaneously in the axilla of four fetal sheep. Safe implantation of the radiotelemeter was technically feasible and the device reliably recorded the fetal electrocardiogram and temperature both intraoperatively and postoperatively. Although many possible routes for access to the fetal circulation have been tried experimentally and clinically for both resuscitation and blood sampling, none have proven satisfactory. We assessed the use of intraosseous access in fetal sheep (n = 6) for both infusion and blood sampling. Access with an intraosseous needle was obtained in both sheep fetuses and human fetal cadavers. Blood gas values (pH, PCO2, and PO2) obtained from the medullary cavity of fetal sheep accurately reflected peripheral venous values. Resuscitation drugs reached the fetal circulation via the intraosseous route: sodium bicarbonate elevated venous bicarbonate levels from 28.4 +/- 1.7 to 31.8 +/- 2.1 mEq/dL (P < .05); injected glucose increased venous glucose levels by 520 +/- 108 mg/dL (P < .01); and injection of calcium chloride elevated venous calcium levels from 11.8 +/- 0.7 to 15.2 +/- 2.2 mEq/dL (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403516 TI - Management of catastrophic neonatal midgut volvulus with a silo and second-look laparotomy. AB - The case of a neonate with midgut volvulus and severe intestinal ischemia extending from the ligament of Treitz to the midtransverse colon is presented. Management consisted of abdominal silo application at the initial exploration to obviate the adverse physiological consequences of increased intraabdominal pressure from reperfusion edema of the intestine. The majority of the intestine was salvaged, and a short segment of ileum was resected. This method of treatment resulted in optimal ventilatory status, renal function, and cardiac performance. The advantages of temporary prosthetic wound coverage in selected cases of midgut volvulus include greater physiologic stability through the avoidance of "intraabdominal hypertension" and the ability to monitor the status of the intestine at the bedside. PMID- 1403517 TI - Neonatal gastrointestinal perforations. AB - Neonatal gastrointestinal perforation has been associated with mortality rates of 40% to 70%. Over the past 20 years, 81 infants (46 boys and 35 girls) were treated for a gastrointestinal perforation at this institution. Perforation occurred from birth to 50 days (average, 8.2 days). Etiologies included necrotizing enterocolitis (NEC) (68%), meconium ileus (10%), and idiopathic gastric perforation (7%). Seventy-six infants underwent surgical exploration and five infants, considered too small or too sick to withstand a laparotomy, were treated with peritoneal lavage only. There were 29 deaths, an overall mortality of 36%. Ninety percent of the death occurred in patients with NEC, while all patients with gastric perforations survived. There has not been a significant improvement in survival in recent years, partly because of an increase in the proportion of NEC-related perforations. However, there is a narrowing of the mortality gap between low birth weight and normal weight infants. As the risk inherent to laparotomy in neonates is decreasing, other factors, such as the underlying etiology or the site of perforation, play a more important prognostic role. PMID- 1403518 TI - Clinical factors affecting mortality in children with malrotation of the intestine. AB - In children with symptoms secondary to malrotation of the intestine, a retrospective statistical study was undertaken to identify factors associated with an increased risk of mortality. Between 1964 and 1989, laparatomy was performed on 182 children. For study purposes, the children were divided into three groups. Group I included 71 patients with an obstruction only in the duodenum. The remaining 111 children, all of whom had midgut volvulus, were further divided; those without gut necrosis (79) into group II, and those with necrosis (32) into group III. One child each died in groups I and II, and 15 in group III. In all children we evaluated the relationship between mortality and age at presentation, presence of associated serious abnormalities, time from onset of symptoms to surgery, and the presence of necrotic bowel. For group III, we considered the influence of percentage of bowel resected on mortality. In these 182 children the factors associated with an increased risk of mortality were presence of necrosis (P < .0001), presence of other abnormalities (P = .0008), and younger age (P = .0084). Time from onset of symptoms to surgery was not associated with statistically increased risk of mortality. The 1% mortality noted in children without intestinal necrosis (group I and II) was related to associated abnormality. For group III the estimated probability of survival ranged from .999 for patients with 10% of intestinal necrosis to .351 for whose with 75% of intestinal necrosis, assuming the best prognostic conditions (patient older than 3 months with no associated serious abnormalities). PMID- 1403519 TI - Gastroschisis wringer clamp: a safe, simplified method for delayed primary closure. AB - When primary abdominal wall closure in a newborn with gastroschisis cannot be accomplished safely, placement of a reinforced Silastic silo facilitates delayed primary closure (DPC). In this report we describe our experience with the gastroschisis wringer clamp (GWC). The GWC is an autoclavable, 140-g, aluminum alloy device reminiscent of an old wringer washing machine. It consists of two apposing serrated rollers that pull the Silastic silo through a slotted base plate. This protects the intestine and converts the circular defect into a vertical slit to ease DPC. The GWC is adjusted daily on the awake newborn in the nursery and the magnitude of each adjustment is gauged by the infant's cardiac and pulmonary status. For the past 10 years we have cared for 116 newborns with gastroschisis. The average birth weight was 2,530 g (range, 1,380 to 3,300 g). Eighty-six infants (74.1%) have undergone primary closure. The remaining 30 infants (25.9%) were treated by placement of a Silastic silo and application of the GWC, forming the basis of this report. The DPC operation was performed an average of 6.7 days (range, 3 to 23 days) following the application of the silo. Extubation was usually possible prior to the DPC, with the mean length of mechanical ventilation being 3.8 days. Three patients developed serious complications including two dehiscences of the silo-fascia interface. There were no deaths in this group of 30 patients. The GWC offers many technical advantages and can be easily reversed when the infant's cardiopulmonary status deteriorates. We advocate its adoption as a method of choice in the newborn with gastroschisis who requires DPC. PMID- 1403520 TI - Unilateral leg edema caused by abdominoscrotal hydrocele: elegant diagnosis by MRI. AB - A 5-month-old boy presented with bilateral hydroceles since birth and right leg edema. An ultrasound of the pelvis showed a 4-cm cystic mass that was diagnosed as a teratoma or cystic hygroma. Magnetic resonance imaging was performed, which showed a dumbbell shaped contiguous, fluid filled mass extending intraabdominally through the inguinal canal from the scrotum. The cystic portion in the right iliac fossa was lying on the right iliac vessels, which were patent. A bilateral hydrocelectomy was performed, and the intraperitoneal sac was completely excised through the inguinal incision. The edema of the right leg disappeared a few days after surgery. PMID- 1403521 TI - Cloacal exstrophy: prenatal diagnosis before rupture of the cloacal membrane. AB - Embryologically, cloacal exstrophy is thought to result from persistence and subsequent rupture of the infraumbilical cloacal membrane during the fifth embryonic week. We report a case of cloacal exstrophy in which a prenatal diagnosis was made prior to rupture of the cloacal membrane. A routine ultrasound at 17 weeks' gestation demonstrated monoamniotic twins. One twin was normal, but the other was found to have a sacral myelomeningocele, "rocker-bottom" feet, splaying of the pubic rami, and a large cystic mass protruding from the infraumbilical anterior abdominal wall. A repeat ultrasound was performed at 22 weeks, with the same findings. At 26 weeks, further examination showed disappearance of the abdominal cyst, a small omphalocele, no demonstrable bladder, and the suggestion of prolapsed bowel inferior to the umbilical cord insertion. After delivery at 34 weeks, the abnormal twin was found to have the typical findings of cloacal exstrophy, myelomeningocele, bilateral lower limb anomalies, and extremely foreshortened small bowel. Rupture of the presumed cloacal membrane after 22 weeks in this case is inconsistent with our current understanding of the embryology of this anomaly, and should stimulate a reexamination of the current concepts. If the characteristic features are recognized, cloacal exstrophy can be diagnosed by prenatal ultrasound, permitting prenatal counseling and appropriate perinatal management. PMID- 1403522 TI - The kidney in the fetal rat model of congenital diaphragmatic hernia induced by nitrofen. AB - This paper explores whether there is a correlation between kidney and lung growths in an experimental model of congenital diaphragmatic hernia (CDH) induced by intragastric administration of Nitrofen (115 mg/kg) in olive oil on time-dated pregnant Wistar rats at the 9th day of gestation. For comparison we used pregnant rats treated with olive oil alone. Twenty-nine normal fetuses from 3 control rats and 24 left CDH fetuses from 6 Nitrofen rats were studied. Fetal (3.6 +/- 0.8 v 4.9 +/- 0.4 g, P < .001) and total lung (2% +/- 0.5% v 2.6% +/- 0.3% of body weight, P < .001) weights were significantly decreased in animals with CDH. Kidneys were also smaller in CDH animals although not significantly (0.7% +/- 0.1% v 0.8% +/- 0.1% of body weight, P = .05) and were also histologically immature. Regression of kidney weight on body weight for both groups yielded regression lines that were identical at analysis of covariance and all data points from the CDH group were within the control group 95% confidence limits. After converting raw data into lung/body and kidney/body weight ratios, no inverse correlation suggesting a feedback mechanism of growth regulation between both organs could be found. Since nitrofen acts through modifications of the thyroid hormone status in both dam and fetus, altered maturation of several organs should be expected although some of them, like the lung, are the leading targets. The present CDH rodent model is probably different from the human malformation in spite of the striking anatomic similarities between them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403523 TI - A rare intrapericardial mass in a neonate. AB - We describe a rare case of a neonate born with an intrapericardial mass composed of extralobar pulmonary sequestration and a cyst of bronchogenic origin. After an uneventful delivery, this full-term newborn was noted to be grunting and indrawing. He remained tachypneic despite adequate management for bilateral pneumothoraces. Diagnostic studies showed a 3 x 3 x 4 cm diameter cystic lesion in the anterior mediastinum causing posterior-lateral displacement of the superior vena cava. The heart itself was structurally normal. Bronchoscopy and esophagoscopy failed to detect any structural abnormalities. At 3 weeks of age, sternotomy and resection of the lesion was performed. The mass was clearly intrapericardial and consisted of sequestrated pulmonary tissue with a unilocular mucus filled bronchogenic cyst. Small systemic tributaries fed the lesion from the posterior-superior aspect. There was no connection with the heart or great vessels. Postoperative recovery was uneventful. PMID- 1403524 TI - Rhabdomyosarcoma arising within congenital pulmonary cysts: report of three cases. AB - Over the past 9 months, three cases of primary pulmonary rhabdomyosarcoma have been treated at British Columbia Children's Hospital. Two patients (aged 24 and 37 months) presented with spontaneous pneumothoraces and had cystic changes in the affected lung on chest radiograph. The third patient (aged 42 months) was evaluated for chronic cough, fever, and failure to thrive. Chest x-ray showed a large mass in the left lower lobe as well as mediastinal adenopathy. All three of these lesions originated within congenital lung cysts, one a peripheral bronchogenic cyst and the others cystic adenomatoid malformations. This report suggests that there is a significant risk for the development of rhabdomyosarcoma within malformed pulmonary tissue. PMID- 1403525 TI - Extracellular fluid and total body water changes in neonates undergoing extracorporeal membrane oxygenation. AB - After being placed on extracorporeal life support (ECLS), newborn patients typically weight 5% to 30% more than their birthweight. Recovery and eventual decannulation from ECLS is associated with a return to baseline weight or birthweight values after a pronounced diuresis. It has been assumed that the increases in weight in these patients are due to increases in extracellular fluid (ECF) and total body water (TBW). This study was undertaken to prove or disprove this hypothesis. ECF space was measured using the compound sodium bromide and TBW was determined with the use of deuterium oxide (nonradioactive heavy water). Fluid compartment measurements were made prior to the institution of ECLS, immediately after placement on bypass, approximately every other day while on bypass, and a final measurement was made once the patient was off bypass. Sodium bromide concentration was analyzed by high-pressure liquid chromatography, and deuterium oxide concentration was measured by the falling drop method. Eight newborns with respiratory failure were placed on either venoarterial (4 patients) or venovenous (4 patients) ECLS for an average of 106 hours (range, 71 to 219 hours). Pre-ECLS TBW was high in the neonates (87% of total body weight v the normal of 75% to 80%). Mean values for each fluid compartment were corrected for the additional volume of the bypass circuit when the patient was on bypass. ECF increased immediately after the institution of ECLS; however, both ECF and TBW decreased during the bypass run, and post-ECLS levels of ECF and TBW were similar to those found prior to ECLS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403526 TI - Resection of the primary tumor is appropriate for children with stage IV-S neuroblastoma: an analysis of 37 patients. AB - Current recommendations for treatment of children with IV-S neuroblastoma (NB) indicate that "supportive care is the cornerstone of therapy" and resection of the primary tumor is not mandated. The presentation and clinical management of 37 IV-S NB patients from three pediatric oncology centers were retrospectively reviewed. The 22 boys and 15 girls presented at an average age of 107 days (range, 4 to 616 days). Primary tumor sites were identified in the adrenal gland in 19 children, the thorax in 5, the retroperitoneum in 4, and 1 each in the pelvis and kidney. At the time of presentation, metastatic disease was documented in the liver (27), bone marrow (19), skin (7), and regional lymph nodes (7). Massive hepatomegaly (below the umbilicus) was demonstrated in 18 patients. Twenty-eight children (76%) have survived on average 90 months following diagnosis. Eight patients (22%) died; six of disease and two of complications of therapy (mean, 9.6 months). One child was lost to follow-up. Only 3 of the 37 patients (8%) were managed solely by supportive care and all are alive. Extirpation of the primary tumor was accomplished in 24 individuals (65%). Twenty patients underwent excision at diagnosis and four had delayed resection with few postoperative complications and no deaths related to resection. One death resulted from progression of disease in a child who had tumor removal. Chemotherapy as a single treatment or in combination with radiation was used in 10 children with three children surviving (30%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403527 TI - Improved outcome utilizing spinal anesthesia in high-risk infants. AB - The development of apnea following general anesthesia in high-risk infants (less than 60 weeks postconceptual age) has been reported up to 37%, prompting the routine admission of these children following minor surgical procedures. One hundred forty high-risk infants (American Society of Anesthesiologists category greater than or equal to 2) were prospectively evaluated after undergoing surgical procedures normally performed as outpatients in low-risk babies. All patients had spinal anesthesia for their operations. The mean gestational age for these infants was 30.8 +/- 3.7 weeks (minimum, 24 weeks) with a mean birth weight of 1,466.0 +/- 638.8 g. The mean postconceptual age and weight at the time of surgery were 44.8 +/- 7.8 weeks and 3,336 +/- 1,242 g, respectively. Difficulty in administering the spinal anesthetic occurred in 6 cases (4.2%). Postoperative complications occurred in 5 children (3.8%). They were: postoperative fever (2), transient bradycardia (2), and apnea (1). The four cases of postoperative fever and bradycardia were insignificant and required no medical intervention. The single case of apnea occurred in a premature infant who received a supplemental dose of intravenous midazolam. Length of operation in these cases ranged from 15 minutes to 95 minutes (mean, 53 minutes), with two incidents of inadequate anesthesia occurring in this cohort. Mean duration of anesthesia was 146 minutes (range, 50 to 240 minutes) and was directly dependent on dosage administration of the agents. These data indicate that the use of spinal anesthesia in high-risk infants is safe and effective for surgical procedures generally performed as outpatients (3.0% minor complication rate, 0.8% major complication rate).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403528 TI - Growth hormone reverses impaired wound healing in protein-malnourished rats treated with corticosteroids. AB - Corticosteroid (CS) administration amplifies the inhibitory effect of protein malnutrition (PM) on wound healing. Abdominal surgery in protein malnourished patients receiving corticosteroids (eg, advanced malignancy, transplant recipients) may be complicated by wound dehiscence or anastomotic breakdown. Although preoperative parenteral nutrition can reduce the incidence of these complications, this is not possible in patients requiring urgent surgical intervention. In a previous report we demonstrated that postoperative growth hormone (GH) administration could restore normal wound healing in PM rats. This study evaluates the effect of GH on wound healing in PM rats treated with CS. Forty-eight female Sprague-Dawley rats weighing 180 to 210 g were divided into four groups: (1) normally nourished; (2) PM only; (3) PM + CS; and (4) PM + CS + GH. PM rats (groups 2 to 4) received 5.5% protein chow every other day for 8 weeks. Control rats (group 1) received 23.4% protein chow for the same duration. Group 3 and 4 rats received prednisolone (2 mg/kg, intramuscularly) during the last 3 weeks of PM. All animals underwent precise 5-cm midline celiotomies. Postoperatively, rats in all groups were given 23.4% protein chow. Group 3 and 4 rats continued to receive CS postoperatively. Group 4 rats were given GH (0.5 mg/d, intraperitoneally) postoperatively for 5 days. Wound testing was performed on the 6th postoperative day after removal of the sutures. A balloon inserted into the peritoneal cavity through the vagina was gradually inflated. The pressure at which the wound disrupted was recorded as the wound bursting strength.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403529 TI - Cultured epidermal autografts: a life-saving and skin-saving technique in children. AB - The recent more widespread availability of cultured keratinocytes has increased their clinical applicability in pediatric surgical problems. In life threatening burns (3 patients) and in elective procedures (3 patients) we have used sheets of cultured epithelial autografts. Body surface area affected ranged from fifteen to 85%. Five patients were successfully treated in one grafting session and one required four sessions. Take of the cultured keratinocytes ranged from 75% to 95%. Follow-up as long as 30 months has shown the skin to be comparable to if not superior to conventional split thickness grafts. The use of cultured keratinocytes allows wound coverage without expansion of the affected body surface area seen with conventional split-thickness skin grafting. Although there is an initial delay in the preparation of the grafts, the overall results have been excellent and suggest the more frequent use of this method. PMID- 1403530 TI - Early induction of IL-6 in infants undergoing major abdominal surgery. AB - Cytokines are immunoregulatory molecules that are important mediators of the host response to stress and infection. Infants and children undergoing major surgery are particularly at risk of developing sepsis and have altered metabolic responses to surgical stress compared to adults. We have investigated the temporal sequence of cytokine responses in six infants (mean age, 11 +/- 7.5 months) undergoing pull-through operation for Hirschsprung's disease and correlated them with hemodynamic and biochemical parameters. Tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured by ELISA preoperatively, intraoperatively (hourly), and 24 and 48 hours postoperatively. IL-6 levels increased significantly in all cases within 2 hours of commencement of the operation (P less than .01) and were maximal 24 hours postoperatively. No significant changes in IL-1 beta levels (mean range, 70 to 110 pg/mL) were seen in these patients. TNF levels were undetectable (less than 20 pg/mL) throughout the study. Cortisol levels were increased in all patients during operation. Serum C-reactive protein levels were first detected 24 hours postoperatively and continued to increase 48 hours postoperatively. Hemodynamically, heart rate increased during the first 3 hours of operation and correlated with increase in IL-6 levels. Blood pressure and temperature changes did not correlate with cytokine levels. This study identifies IL-6 as the earliest detectable cytokine response associated with major surgery in infants. It also suggests that IL-6 can be unregulated, independently of other cytokines, in response to surgical stress. PMID- 1403531 TI - Experience with a nurse practitioner program in the surgical department of a children's hospital. AB - Manpower limitations are occurring in residency programs because of fewer residency positions and increasing governmental regulations. This limitation prompted the development of a program to utilize pediatric nurse practitioners (PNPs) in our Department of Surgery. Two began in September 1989. Their role was similar to that of the junior resident and included collaborative management of patients, admission evaluations, discharges, and a variety of procedures. The impact of this program was evaluated by questionnaire to attending surgeons, house staff, and parents. There were 123 surveys mailed (12 attending surgeons, 46 residents, 65 parents). The overall response rate was 51% (100% attending surgeons, 57% residents, and 38% parents). Only two of the attending surgeons had previous experience working with a PNP. All attending surgeons were enthusiastic about the PNP role in managing their patients and felt the PNP had decreased the workload of the resident. Eighty-three percent did not feel the PNP interfered with resident learning; 17% were undecided. Eleven of 12 felt the PNP had helped communication between them and their patients; one was undecided. The resident responses were assessed by level of training. Among senior residents, 82% felt the PNP had decreased the workload of the junior resident and 91% viewed the PNP as a valuable resource, whereas 87% of the junior residents felt the PNP decreased their workload and 100% felt the PNP was a valuable resource. None of the residents felt the PNP interfered with their learning and 73% of the junior residents and 55% of the senior residents felt the PNP contributed to their learning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403532 TI - The splenic snood: an improved approach for the management of the wandering spleen. AB - A wandering spleen is in constant danger of torsion and infarction. Splenectomy, the traditional treatment, leaves children in danger of postsplenectomy sepsis. Three children with wandering spleens were treated by a new splenopexy technique, the splenic snood. After detorsion, the spleens were wrapped in polyglycolic mesh and anchored by the mesh subdiaphragmatically in the left upper quadrant. All have retained their spleens which have remained where anchored up to a 4-year follow-up. The simplicity and technical ease of the splenic snood operation recommend it as an improved method to avoid splenectomy and safely normalize intraabdominal anatomy in the management of the wandering spleen. PMID- 1403533 TI - Response to Haemophilus influenzae type B conjugate vaccine in children undergoing splenectomy. AB - Asplenic children are at increased risk for serious infection with polysaccharide encapsulated bacteria including Haemophilus influenzae type b (HIB), Streptococcus pneumoniae, and Neisseria meningitidis. Immunization with polysaccharide vaccines is recommended for children undergoing splenectomy. In 1987 a new more immunogenic HIB vaccine was licensed in the US to replace the pure HIB polysaccharide vaccine that was licensed in 1985. This polysaccharide conjugate vaccine consists of the HIB polysaccharide linked to a protein carrier, diphtheria toxoid. Therefore, we evaluated the immune response of children undergoing splenectomy to HIB-conjugate vaccine. Thirteen children (7 with Hodgkin's disease, 4 with idiopathic thrombocytopenia, 2 with hereditary spherocytosis) aged 3 to 19 years were immunized with HIB-conjugate vaccine prior to splenectomy and serum was obtained following splenectomy. In addition, 15 healthy control children aged 2 to 14 years were immunized with the pure polysaccharide HIB vaccine for comparison. The patients undergoing splenectomy who received the HIB-conjugate vaccine had a geometric mean IgG anti-HIB antibody concentration of 48,106 ng/mL versus 10,786 ng/mL for the control patients who received the pure polysaccharide vaccine (P = .01). The presumed protective level of antibody is 1,000 ng/mL and all children were well above this concentration. Therefore, we propose that children undergoing splenectomy be immunized with an HIB-conjugate vaccine. PMID- 1403534 TI - Successful splenorenal shunt for emergent control of variceal bleeding in a small child. AB - A 8.6-kg, 10-month-old boy with idiopathic cavernous transformation of the portal vein developed variceal hemorrhage refractory to nonoperative management. A distal splenorenal shunt was performed while the bleeding was controlled with balloon tamponade. Hemorrhage was successfully controlled with no recurrent bleeding and the shunt remains patent at 1 year of follow-up. PMID- 1403535 TI - The risk of abdominal operations in children with ventriculoperitoneal shunts. AB - Ventriculoperitoneal (VP) shunts are the operations of choice for patients with hydrocephalus in most pediatric hospitals. Children with VP shunts frequently undergo abdominal operations unrelated to their shunts, which might lead to shunt infections or to malfunctions related to adhesions. Although prophylactic antibiotics are usually used in this setting, there are few data to support their use, or to assess other risks to the shunt from the abdominal procedures. Consequently, we reviewed the records of 37 children with VP shunts who underwent a total of 44 abdominal operations. In 8 cases, the genitourinary (GU) tract was opened (ureteral reimplantation, bladder augmentation, nephrectomy), whereas in 18 patients the gastrointestinal (GI) tract was opened (appendectomy, gastrostomy, small/large bowel resection). In 18 operations neither GI nor GU tract was opened (lysis of adhesions, herniorrhaphy, orchiopexy). Antibiotic coverage was highly variable: 9 received no antibiotics, 9 received antibiotics only postoperatively, 4 were given antibiotics only preoperatively, and in 22 cases antibiotics were given both preoperatively and postoperatively. One shunt that was involved in a periappendiceal abscess was exteriorized and later successfully replaced. In the remaining cases, no episodes of shunt infection or malfunction occurred in 1 to 10 years of follow-up. Likewise, no abdominal cerebrospinal fluid pseudocysts formed as a result of abdominal adhesions. These data demonstrate that children with VP shunts can safely undergo abdominal operations, even when the GI or GU systems are opened, with minimal risk of shunt infection or malfunction. Rigid protocols of prophylactic antibiotics cannot be supported by this series. PMID- 1403536 TI - Mycotic thromboaneurysmal disease of the abdominal aorta in preterm infants: its natural history and its management. AB - Five infants with mycotic complications of umbilical artery catheterization were evaluated with abdominal ultrasound and followed serially to document their natural history. Methicillin-resistant Staphylococcus aureus was always the infecting organism. There were one female and four male infants and they weighed between 900 and 1,200 g at birth. While two of the catheters were positioned in the abdominal aorta, three were located above the diaphragm. The predominate signs and symptoms included: thrombocytopenia, unexplained anemia, renal failure, hypertension, and embolic phenomena to the toes. Real-time ultrasound always proved sufficient for diagnosis. Serial studies detected the initial aortic thrombosis in three patients and accurately documented its progression to aneurysmal disease over 10 days in one patient and 17 days in another. Three of the infants were diagnosed with aneurysms at their initial examination. Of the five patients, three were treated nonoperatively and died of complications of their aortic disease. One patient was discovered at operation to have necrotic ischemic intestine. Aortic repair was postponed and he died of septic complications. The remaining patient underwent a PTFE interposition graft and survived for 6 months, dying of pulmonary failure with autopsy confirmed graft patency. PMID- 1403537 TI - Mucosal morphology in isolated bowel segments: importance of exposure to luminal contents. AB - An isolated bowel segment (IBS) is a loop of intestine that has been freed from its mesenteric attachment after the development of vascular collaterals between the antimesenteric surface of the gut and the host organ. Surgical creation of such artificially vascularized isolated bowel segments is of interest to researchers for a variety of studies, and may be useful in the treatment of short bowel syndrome, allowing longitudinal division of the remaining small bowel to double its length. We created four surgical variants to study the ability of the collateral blood supply to maintain mucosal integrity in the presence or absence of normal luminal contents. In all groups, a collateral blood supply was created in a 5- to 7-cm segment of adult rat jejunum by hepatoenteropexy (Iowa model II). In Thiry-Vella (T-V) and isolated bowel segment (IBS) rats, this segment was exteriorized at both ends to exclude luminal contents. Control and IBS in continuity (IBS-C) loops were left in continuity. The mesentery of IBS and IBS-C rats was divided 5 weeks later, leaving the experimental segment entirely dependent on the collateral circulation. All animals were harvested at 7 weeks after the initial surgery. Tissues were analyzed for mucosal weight, protein content per centimeter of bowel, length of villi, depth of crypts, DNA content, and sucrase activity. We found that segments retaining luminal continuity had significantly higher mucosal weight and DNA content per centimeter of bowel compared with exteriorized loops. PMID- 1403538 TI - Laparoscopic cholecystectomy in children: initial experience and recommendations. AB - Our initial experience with laparoscopic cholecystectomy in children and the modification of techniques required for pediatric surgical patients is reported. Six children aged 6 to 17 years underwent laparoscopic cholecystectomy for symptomatic cholelithiasis. All patients had biliary colic and did not require concomitant intraabdominal surgical procedures. Average operative time was 89 minutes; none were converted to open cholecystectomy. One patient returned home the evening of surgery, two patients were discharged the following morning, and two patients were discharged 2 days following the procedure because of their distance from home. There were no complications. All patients have remained asymptomatic on follow-up of 1 to 5 months. Based on this initial experience, several changes in the technique as reported in adults are recommended. Due to the softness and laxity of the anterior abdominal wall, an infraumbilical incision for the 10-mm camera trocar is more cosmetically acceptable and just as efficient. There is a smaller intraabdominal space with which to work, tempting one to overinflate the abdomen for better visualization. Care should be taken to ensure that the intraabdominal pressure does not exceed 15 mm Hg despite the small volumes required to do so. Placement of the second epigastric incision is more inferior and lateral than the standard recommendation for adults. The cystic duct must be controlled as early as possible in the operative course to prevent egress of stones from the gallbladder into the common duct. In one patient, these migrating stones were milked back into the gallbladder and a second clip placed. PMID- 1403539 TI - The atonic baggy rectum: a cause of intractable obstipation after imperforate anus repair. AB - Three children with successful imperforate anus repairs had chronic, intractable obstipation and recurrent fecal impaction refractory to diligent medical therapy. All had massive stool-filled rectums up to 14 cm in diameter on abdominal radiographs. They responded well to resection of the baggy atonic rectum with low anterior anastomosis. The massively dilated atonic rectal pouch in some children with repaired imperforate anus can demonstrate abnormal motility characterized by poor peristalsis and propulsion. This results in recurrent obstipation, impaction, and soiling refractory to the usually successful medical management. PMID- 1403540 TI - Sacrococcygeal teratoma: the experience of four decades. AB - To determine the extent of progress in the treatment of sacrococcygeal teratomas (SCTs), we evaluated the experience with 73 patients over 40 years. The medical records of the children were reviewed for demographics, histology, clinical course, and outcome. Therapy differed depending on the type of SCT, histology, and decade of diagnosis. The female:male ratio was 4.2:1 and did not vary significantly with the histology of the tumor. Fifty-seven patients presented with benign disease. There were five recurrences in this group, only one of which did not have an initial coccygectomy. One tumor, originally thought to be benign with immature elements, had a local recurrence at 7 months, 10 months, and 16 months after the original operation and was discovered to have embryonal carcinoma with nodal involvement. This child was treated with chemotherapy and is disease-free at 7 years. Morbidity in the benign group included 3 postoperative wound infections. Three infants died, one before operation with beta-hemolytic Streptococcus sepsis. Two neonates died in the early postoperative period, one on day 1 with a ruptured subcapsular hematoma of the liver, and the second on day 2 with disseminated intravascular coagulation/sepsis. Benign SCT occurs at a younger age than malignant tumors. The average age of presentation of benign tumors is 20 days versus 468 days in children with malignant disease. The technique of wide resection of benign lesions with coccygectomy is helpful in preventing recurrence and has changed little over the last four decades. Malignant SCT occurred in 16 children (22%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403541 TI - Prognostic factors and outcome in patients 21 years and under with colorectal carcinoma. AB - This study aims to identify significant predictors of survival in pediatric and adolescent colorectal carcinoma. We retrospectively analyzed our experience with 29 histologically verified cases, of which 20 were resected for cure. Variables analyzed as predictors of survival included: (1) resectability, (2) regional nodal involvement, (3) depth of invasion, (4) grade, and (5) interval from symptom onset to diagnosis. Signet ring or anaplastic lesions were considered high grade. Survival curves were generated on both the overall group and those resected for cure. Multivariate analysis was performed on the overall group. The median age at diagnosis was 19 years (range, 10 to 21). Median follow-up in survivors was 4.7 years. Signet ring tumors occurred in 45% and another 24% were poorly differentiated. Seventy-six percent presented with regional lymph node metastases. The median survival for the overall group was 16 months, whereas that for those undergoing complete resection was 33 months. In patients undergoing resection for cure, grade (P = .005), regional nodal involvement (P = .007), and depth of invasion (P = .03) were significant predictors of outcome in univariate analysis. In the overall group these variables as well as resectability and distant metastases were significant in univariate analysis. In multivariate analysis high-grade lesions and lymph node involvement were highly correlated, as were resectability and metastases. Thus, either variable (but not both) of each pair added information to the multivariate model. In patients resected for cure, positive nodes or high histological grade became the only significant predictors of survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403542 TI - Transhiatal esophagectomy and colonic interposition for caustic esophageal stricture. AB - From January 1986 through 1990, 70 children (42 boys, 28 girls) with esophageal stricture resulting from ingestion of caustic potash underwent simultaneous esophagectomy and colonic interposition utilizing the transhiatal esophageal approach. At the time of the procedure, their ages ranged from 14 months to 6 years (mean, 3.2 years). Thoracotomy was needed in one patient due to accidental injury to the tracheal during esophageal mobilization. There were 3 deaths from respiratory failure. Otherwise, morbidity was low, and there were satisfactory long-term functional results. The use of isoperistaltic left colon based on both ascending and descending branches of the left colic vessels resulted in survival of all grafts. End-to-side esophagocolic anastomosis decreased the incidence of both postoperative leak (2 instances) and late stenosis (1 case needed surgical revision). Construction of a length of colonic graft equal to the gap between the esophagus above the stricture and the stomach and fixation of the graft to the edge of the esophageal hiatus reduced the incidence of late colonic redundancy in the chest; this did occur in 4 cases but was not associated with dysphagia. Routine pyloroplasty and anterior cologastric anastomosis to the gastric antrum contributed to the absence of gastrocolic reflux and peptic ulceration in this series. PMID- 1403543 TI - Transventricular dilation for critical aortic stenosis in neonates. AB - Critical aortic stenosis (CAOS) is not compatible with life when the ductus arteriosus closes. We have treated 11 consecutive cases with isolated CAOS. Symptom presentation was in the early neonatal period and diagnosis was made noninvasively at a mean age of 4 days. All were operated on with transventricular dilation (TVD) at a mean age of 4.7 days. There was no early mortality. There were two late deaths due to fibroelastosis. Both had the smallest aortic anulus diameter (5 mm). Two other patients had aortic root replacement, one at the age of 6.5 weeks due to intractable heart failure, and the other at the age of 3 months due to increasing gradient. In these two cases elective surgery was made possible by a successful TVD in the early neonatal period. TVD in this material was not associated with any early mortality, which makes this procedure a good alternative in the treatment of CAOS. PMID- 1403544 TI - Prolonged extracorporeal support for nonneonatal respiratory failure. AB - Extracorporeal membrane oxygenation (ECMO) is effective for newborns with pulmonary failure unresponsive to conventional therapy. However, ECMO for the older child and adult has been controversial and not widely utilized. Over 4 years, 24 patients (aged 4 months to 16 years; 11 boys, 13 girls) underwent venoarterial ECMO (duration, 7 to 19 days) for respiratory failure. The diagnoses were: viral pneumonia (7), hydrocarbon aspiration (6), sepsis with adult respiratory distress syndrome (ARDS) (2), bacterial pneumonitis (2), tracheal stenosis (1), bilateral pulmonary contusion (1), diaphragmatic hernia with ARDS (1), ketoacidosis with ARDS (1), pulmonary artery injection of hydrocarbon (1), drowning (1), and epiglottis with barotrauma (1). Pre-ECMO blood gas ranges (and means) were PO2 18 to 65 (46), and PCO2 47 to 112 (65). Nineteen patients received dopamine, dobutamine, or other inotrope for associated cardiac and/or renal failure. Cannulation for ECMO was through neck or groin vessels in 17, and sternotomy in 7. ECMO flow rates were 150 to 250 mL/kg/min, to maintain PO2 greater than 100 and PCO2 less than 40. Nine patients (41%) survived ECMO, with eight long-term survivors, (4 hydrocarbon aspiration or injection, 1 pulmonary contusion, 1 viral pneumonia, 1 ARDS, 1 barotrauma), three of whom have mild neurological deficit. All patients with sternotomy, and 8 of 15 with neck and/or groin cannulation, required 1 to 5 explorations for hemorrhage while on ECMO. All survivors had primarily pulmonary failure; patients with combinations of pulmonary, cardiac, and renal failure did not survive. ECMO can be life-saving in the child with isolated pulmonary failure, but its efficacy in patients with multiorgan failure is uncertain. PMID- 1403545 TI - Surgical complications and procedures in neonates on extracorporeal membrane oxygenation. AB - We report our experience from May 1985 to January 1991 with surgical complications and procedures performed in neonates on extracorporeal membrane oxygenation (ECMO) (218 venoarterial and 7 venovenous bypass). Eleven children older than 1 month were excluded. Total complications were 96 in 67 patients and included: bleeding (37), problems with initial cannula placement (17), thrombus formation (15), hemothorax, pneumothorax, or effusions (11), mechanical problems (11), and miscellaneous (5). Forty-eight procedures were performed in 37 patients while on ECMO. These were recannulation or reposition of cannulas (14), tube thoracostomy (11), cardiac surgery (6), cardiac catheterization (4), repair of congenital diaphragmatic hernia (5), thoracotomy (4), and others. Twenty-eight complications occurred in 15 of the 27 patients who died. Mortality rate was 12% for the entire group. Primary causes of death were hypoplastic lung (11), cardiac (8), sepsis (4), intraventricular hemorrhage (2), and pulmonary hypertension (2). No deaths were due solely to complications except for the two patients with intraventricular hemorrhage. Mortality in neonates who had complications while on ECMO was significantly higher (P less than .005) than in patients without complications. Hemorrhagic and thoracic complications were associated with higher mortality (P less than .001). Mortality was not affected by mechanical problems, thrombus formation, or catheter-related problems. While on ECMO cardiac defects, diaphragmatic hernia, lobar emphysema, and other conditions can be safely corrected. The use of echocardiography to position the cannulas, better control of coagulation factors and improvement in equipment may ultimately decrease complications. PMID- 1403546 TI - Echocardiography in the preoperative evaluation of vascular rings. AB - Vascular rings may produce tracheal and/or esophageal compression in infants and children. Traditionally recognized fluoroscopically, the exact anatomy of the ring and appropriate surgical correction are determined intraoperatively. The role of preoperative echocardiography was examined. Twenty patients with symptomatic vascular rings were evaluated preoperatively with echocardiography at this institution. Their ages ranged from 10 days to 11 years (mean, 17 months). There were 9 boys and 11 girls. Most (17/20) presented with respiratory symptoms in the first year of life, although in 3 patients dysphagia was the primary complaint (at birth, 4 months, 9 years). All underwent initial evaluation with a barium esophagogram prior to the echocardiogram. Surgical correction was subsequently performed and the exact anatomy identified. All barium esophagograms were interpreted prospectively as demonstrating a "vascular ring." Although often suspected fluoroscopically, the actual type of ring was correctly identified by echocardiogram in all cases including determination of the dominant arch and associated anomalies. The types of vascular rings included double aortic arch (10), right aortic arch with left ligamentum arteriosum and/or aberrant left subclavian artery (6); aberrant right subclavian artery (2), and pulmonary artery sling (2). Barium esophagogram remains the best screening test for children in whom a vascular ring is suspected. However, echocardiography is a useful noninvasive complementary examination to confirm the diagnosis, clarify anatomy, and exclude other major intracardiac pathology prior to surgical correction. PMID- 1403547 TI - Pericardial flap interposition for the definitive management of recurrent tracheoesophageal fistula. AB - From 1974 to 1988, six children with fistula recurrence following primary tracheoesophageal fistula (TEF) repair have been managed at our hospital. Reclosure of the fistula with pleural flap interposition was used as the initial corrective procedure in five patients, with an 80% incidence of second TEF recurrences. Due to these discouraging results, we have abandoned this technique and instead favor fistula reclosure with interposition of a pedicle of vascularized pericardium between the esophageal and tracheal suture lines. The pericardial pedicle is easy to mobilize, effectively isolates the tracheal and esophageal suture lines, and eliminates the often difficult task of finding sufficient pleural tissue for fistula interposition in small infants. Furthermore, the vascularized pedicle serves as a template for the ingrowth of neomucosa from the existing esophageal mucosa should an anastomotic leak occur. Since adopting this approach, we have used this technique on four children, three of whom had second recurrences after pleural interposition, and have had no evidence of recurrent fistula formation at follow-up ranging from 2 to 6 years. With at least a 20% incidence of second recurrences reported following conventional management with fistula closure and pleural interposition, we believe use of a pericardial flap in the management of the recurrent TEF is the most appropriate surgical procedure. PMID- 1403548 TI - Delayed primary anastomosis for esophageal atresia: 18 months' to 11 years' follow-up. AB - In 1977 we started treating babies with isolated esophageal atresia by delayed primary anastomosis and in 1981 reported our early experience in five cases treated between 1977 and 1979. Since 1979, 11 further consecutive cases have been managed by initial gastrostomy followed by delayed primary esophageal anastomosis. Their mean gestation was 35 weeks (range, 28 to 40 weeks) and mean birth weight was 2,040 g (range, 1,140 to 2,720 g). The esophageal gap between the two ends when assessed initially at fluoroscopy ranged from 2.2 to 4.5 cm (mean, 3.2 cm). Age at delayed primary anastomosis ranged from 6 to 20 weeks. Anastomotic leak occurred in three babies in the immediate postoperative period and all were successfully managed conservatively. Eight of the 11 patients developed anastomotic strictures; seven cases required 1 to 5 esophageal dilatations. One patient who did not respond to multiple esophageal dilatations required resection of an esophageal stricture. One patient died at 15 months of age of unrelated causes. The 10 surviving patients have been followed-up from 18 months to 11 years. At follow-up, seven patients were eating normally. Three patients had swallowing difficulties and all three were found to have esophageal strictures on barium swallow, two of them also had gross esophageal reflux and hiatus hernia. The height and weight in the 10 patients varied from 3rd centile to 75th centile. Delayed primary anastomosis is feasible in cases of isolated esophageal atresia and the patient's own esophagus is the best. A more aggressive approach should be applied to gastroesophageal reflux in these patients. PMID- 1403549 TI - Repair of long tracheal defects with cryopreserved cartilaginous allografts. AB - Tracheoplasties with various autografts (cartilage, periosteum, pericardium) have been used in the treatment of long-segment tracheal stenosis. Previous studies have shown that cartilage allografts survive transplantation on a long-term basis in various sites of the body. In this study we set out to determine if cryopreserved cartilage and cryopreserved tracheal allografts would survive when used to cover tracheal defects in animals. A rectangular defect (2.8 +/- 0.3 cm long and incorporating 50% of tracheal circumference) was created in the thoracic trachea of 18 piglets. The defect was covered with the excised tracheal segment in 6 (group A, control group), with a cryopreserved tracheal allograft in 6 (group B), and with a cryopreserved cartilage allograft harvested from the scapula in 6 (group C). The allografts were cryopreserved, by a standard slow freezing technique, at -80 degrees C for more than 21 days. All animals survived the grafting procedure and were killed after 2 months. None had signs of airway obstruction. Using the trachea above the defect as the standard, the mean sagittal narrowing of the airway in the repaired trachea was 0.4 mm in group A, 0.7 mm in group B, and 0.6 mm in group C; the coronal diameter in normal and grafted trachea was similar. The lumen of all grafts was lined by regenerating respiratory epithelium, and cilia were seen in many. Some cartilage was reabsorbed in group A and B but cartilage islands were present in all. In group A, reabsorption of cartilage was minimal. These findings suggest that segments of trachea or cartilage allografts can be cryopreserved, stored, and, subsequently, used when necessary for tracheoplasty. PMID- 1403550 TI - Severe tracheomalacia associated with esophageal atresia: results of surgical treatment. AB - This study reviews our experience from 1977 to 1991 with 32 children born with esophageal atresia and tracheoesophageal fistula (EA-TEF) who later underwent surgery for severe tracheomalacia. Indications for surgery included dying spells (21), inability to extubate the airway (nasotracheal tube 5, tracheotomy 3), and recurrent pneumonia (3). Diagnosis was confirmed by chest x-ray, esophagogram, and bronchoscopy. Aortopexy was performed in 31 of 32 children; a splint without aortopexy was used in one older girl. Splinting was also necessary in two of the 31 at the initial operation, when aortopexy failed to prevent tracheal collapse. There were four initial failures. Currently, 29 children are well (median follow up, 6.6 years). Two have a tracheostomy in place, and one, who had a vascular ring divided after aortopexy, died at home of unknown cause 1 month later. These findings indicate that aortopexy provides long-term relief of severe symptoms of tracheomalacia associated with EA-TEF in almost all affected children. When aortopexy fails, the insertion of an airway splint may succeed; otherwise, tracheostomy is necessary. PMID- 1403551 TI - The balloon posterior tracheal split: a technique for managing tracheal stenosis in the premature infant. AB - Congenital tracheal stenosis (CTS) in the premature infant almost invariably leads to death for lack of effective reconstructive techniques. We hypothesized that the complete or near complete cartilaginous rings of CTS have a weak point in the posterior portion. Aggressive balloon dilation would result in a posterior longitudinal disruption of the trachea, and an expanded tracheal wall would be created after an appropriate period of endotracheal stenting. Three premature infants with multiple anomalies and CTS were treated with endoscopic posterior tracheal splitting, dividing the trachea as predicted. Although two died of complications of congenital heart disease 2 weeks after the procedure, the third child is alive and well at 9 months of age without airway symptoms. The posterior tracheal wall also split when we performed the procedure in a fresh cadaveric CTS patient. We believe that balloon dilation may prove to be a valuable technique in the treatment of premature infants with congenital or acquired tracheal stenosis and/or in children with such complex diseases that major surgery is precluded. PMID- 1403552 TI - Acquired lobar emphysema (overinflation): clinical and pathological evaluation of infants requiring lobectomy. AB - Acquired lobar "emphysema" (overinflation) (ALE) is an increasingly recognized complication of advanced bronchopulmonary dysplasia (BPD). To refine current concepts regarding patient management and pathogenesis, we examined clinical and pathological features of six infants with ALE who did not have obstructing intraluminal lesions and who underwent lobectomy after failing nonoperative management. All had severe neonatal respiratory distress and required prolonged ventilatory support (average, 2 months) with peak inspiratory pressures greater than 30 mm Hg and 100% oxygen. ALE developed between 3 weeks and 20 months of age (median, 5 months), with lobar hyperinflation, atelectasis, and mediastinal shift. Selective bronchial intubation provided only transient benefit. Videobronchoscopy demonstrated no intraluminal obstructing lesions in five patients. In one child, ALE became clinically apparent only after laser excision of an endobronchial cicatrix. All infants had bronchomalacia with the involved lobar bronchus being most severely affected. Ventilation-perfusion scans demonstrated severe impairment of both ventilation and perfusion in the involved lobes. The decision to perform lobectomy was based on clinical parameters and failure of non-operative management. After lobectomy, all children dramatically improved. However, only three of six were alive 2 to 3 years later; one infant died of unrelated causes at 6 weeks; and two died of progressive respiratory insufficiency 13 and 24 months postlobectomy. Microscopic evaluation of the lung demonstrated findings of late-stage BPD with peribronchial and interstitial fibrosis, parenchymal overinflation, and alveolar septal disruption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403553 TI - Reduced-size lung transplantation from adult to neonatal sheep. AB - Lung transplantation continues to be limited by donor availability. This shortage is particularly acute in the pediatric population. A model was developed in sheep to simulate human pulmonary transplantation from adults into newborns. Pulmonary allografts were performed in 8 neonatal lambs (less than 10 days old) weighing between 2.5 and 5 kg. Unrelated adult sheep donors were used (weighing 55 to 82 kg). The recipient body weight was approximately 6% that of the donor, but ranged from 4% to 8%. Ipsilateral or contralateral upper lobe allografts were used, although the latter required inversion prior to implantation. All venous anastomoses utilized left atrial cuffs. The pulmonary arterial and bronchial anastomoses were constructed end-to-end. Following implantation the lobes were further contoured to fit within the recipient hemithorax using a linear surgical stapler. Animals were immunosuppressed with cyclosporine. Two animals died 1 week postoperatively but the remaining six survived 1 to 5 months. Postoperative lung scans at 10 to 14 days confirmed satisfactory ventilation and perfusion of the allografts. All vascular anastomoses were intact at postmortem examination. Primary bronchial healing accomplished without an omental wrap. We conclude that successful lung transplantation can be performed from adult donors into neonatal recipients. Preservation of the maximal arterial and venous length during native pneumonectomy is essential to allow matching of the vascular cuffs. Short donor lobar bronchi may be responsible for the reliable primary healing. Improved immunosuppression will be required to assess long-term function and growth of these reduced-size allografts. PMID- 1403554 TI - Experience with a total muscle-sparing approach for thoracotomies in neonates, infants, and children. AB - We have adopted a total muscle-sparing technique for thoracotomies in infants and children. The technique preserves the latissimus dorsi and serratus anterior muscles and provides excellent exposure for most thoracic and mediastinal operations. Thirty-two such procedures have been performed with only one complication, a small wound seroma. Use of this technique may not only decrease postoperative pain and splinting, but may decrease the incidence of scoliosis and muscle dysfunction found in children having undergone thoracotomies as infants. PMID- 1403555 TI - Biology of fetal wound healing: collagen biosynthesis during dermal repair. AB - The rapid restoration of tissue integrity and breaking strength in healing fetal wounds is mainly a function of fetal wound collagen. In this study, the fetal and adult tissue responses to injury were characterized in terms of changes in collagen biosynthesis. Linear wounds and unwounded skin were incubated with radioactive proline, and collagen synthesis was measured as isotope incorporation into collagenase-sensitive protein. Likewise, noncollagen protein synthesis was represented by isotope incorporation into collagenase-resistant protein. Adult wounds demonstrated a preferential stimulation of collagen as compared with noncollagen protein synthesis after wounding. In contrast, both collagen and noncollagen protein synthesis were significantly elevated in the fetus during the first 5 days postwounding. Despite marked increases in fetal wound collagen synthesis above both unwounded fetal skin and adult wound levels, fetal wounds exhibited no evidence of excessive collagen deposition or scar formation after wounding. These findings suggest that the fetal response to tissue injury is a function of the distinctive qualities of fetal fibroblasts associated with the extracellular wound matrix and may involve rapid collagen turnover and degradation. PMID- 1403556 TI - Fetoscopic surgery for the treatment of congenital anomalies. AB - Fetoscopic techniques may broaden the indications for prenatal surgical intervention by obviating the risks of hysterotomy. For example, congenital obstructive uropathy has been treated by open vesicostomy and percutaneous catheter placement. The open approach is appropriate only for highly selected fetuses because of the inherent risks, whereas catheter drainage, though a safer procedure, is only useful for short-term therapy late in gestation due to frequent catheter obstruction and migration. The natural history of congenital obstructive uropathy mandates the need for improved therapy earlier in gestation, in order to salvage fetuses who would otherwise die of renal failure and pulmonary hypoplasia. We have developed a potential solution to this problem in which surgery is performed on the fetus without the risks of hysterotomy. Endoscopic fetal surgery uses a telescopic lens and operating instruments that are passed through small "ports" in the uterus. A bubble of CO2 is used to displace amniotic fluid and provides excellent visualization in a magnified field. This approach is considerably less invasive than open fetal surgery and, therefore, is less likely to provoke preterm labor. In this study we corrected obstructive uropathy in midgestation fetal lambs using a new, expandable wire mesh stent that is placed endoscopically and should provide more reliable bladder drainage than existing catheters. The fetoscopic surgical approach can potentially expand the indications for in utero surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. As a consequence, the potential now exists to correct non-life-threatening malformations in utero. PMID- 1403557 TI - Postoperative apnea in infants. AB - This is a review of 127 neonates evaluated for postoperative apnea and bradycardia (A&B) after inguinal surgery. The patients could be divided into three groups based on postconceptional age (PCA) at operation. Ten of 29 patients operated on at PCA of 33 to 39 weeks developed episodes of A&B. Preoperative assessment was not reliable in their identification. In the second group of 54 patients at PCA 40 to 44 weeks, 8 developed A&B, whereas in the third group of 44 patients at PCA of 45 to 60 weeks 1 patient developed A&B. In the latter two groups preoperative assessment identified all patients at high risk. We conclude that after PCA of 40 weeks patients at risk for A&B can be identified preoperatively. Patients operated on up to 39 weeks PCA should all be observed in the hospital. PMID- 1403558 TI - Operative intervention for pediatric liver injuries: avoiding delay in treatment. AB - To identify the physiological and anatomic factors that characterize the need for operative management of blunt pediatric liver injuries, the case records of 106 pediatric trauma victims with liver injuries over a 6-year period were reviewed. Sixty-nine patients were managed without operation (nonoperative) and 37 underwent operation, 7 with penetrating and 30 with blunt liver injuries. Of these 30 patients, 21 underwent laparotomy due to blunt liver injuries (operative); the remaining 9 patients required operation due to associated intraabdominal injuries. Nine (45%) of the 21 operative patients had major hepatic vein or retrohepatic vena caval injuries, 7 of whom died. Overall mortality was 9.4% (10/106). When nonoperative and operative groups were compared, those who underwent laparotomy due to blunt liver injuries: (1) had significantly lower Champion and Pediatric Trauma Scores due to multisystem injury; (2) had 25% or greater lobar disruption with pelvic blood collections on computed tomography scan; (3) underwent early transfusion within 2 hours of admission (18/21); and (4) were frequently found to have a major hepatic vein or retrohepatic vena caval injury at the time of operation. Only one patient successfully managed without operation received greater than 30 mL/kg of blood products within 24 hours of admission. As selective nonoperative management of pediatric liver injuries gains widespread acceptance, the identification of factors that predict the need for operative intervention will limit the potential risks of delay in treatment. PMID- 1403559 TI - Sarcomas of the flexor fossae in children: is amputation necessary? AB - Successful management of sarcomas of the extremities in children implies not only achievement of local control but also satisfactory function and maintenance of the growth potential. The popliteal and antecubital fossae, because of their complex neurovascular anatomy, all of which is essential, make resection with satisfactory margins difficult. We reviewed our experience with 14 patients (3 to 20 years old; median, 13 years) with soft tissue sarcomas arising in the popliteal (11 patients) or antecubital (3 patients) fossae. There were four rhabdomyosarcomas (3 alveolar, 1 embryonal) and 10 other sarcomas, the most frequent being synovial sarcoma (5 patients). Chemotherapy was given to all patients with rhabdomyosarcomas. The one patient presenting with metastatic disease was treated, after biopsy of the primary, by chemotherapy and radiation and survived 21 months. In three patients, the primary management was an above the-knee amputation and two of three survived (3 and 43 months). In 10 patients a wide local excision of the primary tumor was performed. Radiation therapy was administered to five, either as external beam (3 patients) or as brachytherapy (2 patients). In this group, there were no local recurrences. Four patients remain free of disease (4 months to 18 years) and one developed pulmonary metastasis. Among the five non-irradiated patients, three developed local recurrences, requiring above-the-knee amputation for disease. The fourth patient relapsed in the lung and only one of the five is free of disease at 36 months. Of the 8 patients not treated with amputation, one acquired a leg length discrepancy, which required correction, and one has a minimal extension deficit of the knee.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403560 TI - Allopurinol prevents intestinal permeability changes after ischemia-reperfusion injury. AB - Under normal conditions the intestinal mucosa is impermeable to potentially harmful materials from the intestinal lumen. Mucosal disruption promotes bacterial translocation, which is postulated to be a fuel source for sepsis and multiorgan failure. We have previously demonstrated that mesenteric ischemia reperfusion (I/R) injury increases intestinal permeability (IP); however, the mechanism remains unclear. This study was designed to examine the hypothesis that changes in IP, after I/R injury, are mediated by xanthine oxidase-generated, oxygen-derived free radicals. Thirty-three Sprague-Dawley rats (weighing 300 to 400 g) were included in this study. Group 1 (n = 10) received enteral allopurinol, a xanthine oxidase inhibitor, 10 mg/kg daily for 1 week prior to mesenteric ischemia. Group 2 consisted of 11 untreated, ischemic animals. Groups 1 and 2 were subjected to superior mesenteric artery occlusion with interruption of collateral flow for 20 minutes to produce ischemic injury to the intestine. An additional 12 rats (group 3), served as nonischemic controls (sham). A loop of distal ileum was isolated and cannulated proximally and distally to allow luminal perfusion with warmed Ringer's lactate at 1 mL/min. IP was determined in all groups by quantitatively measuring the plasma-to-luminal clearance of chromium (51Cr)-labeled ethylenediaminetetraacetate (EDTA) at baseline, during ischemia and 20, 40, and 60 minutes after reperfusion. Complete ischemia produced significant increases in IP over baseline values in the untreated rats (group 2, baseline: 0.49 +/- 0.006, ischemia: 0.149 +/- 0.039) compared with sham rats (baseline: 0.41 +/- 0.006; ischemia: 0.047 +/- 0.009) or allopurinol-treated rats (baseline: 0.098 +/- 0.020, ischemia: 0.073 +/- 0.012, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403561 TI - Hypoxia-induced bacterial translocation in the puppy. AB - Because hypoxia is one of the most common major stresses to which a neonate is exposed, we postulated that it alone might be the cause of intestinal bacterial translocation, which could be the underlying etiology of neonatal sepsis. An animal model, in which hypoxia is the sole stress, was developed in our laboratory and tested in 18 puppies to determine the effect of hypoxia and reoxygenation on intestinal bacterial translocation. In group I (n = 8), following laparotomy and cannulation of the superior mesenteric vein (SMV), the FIO2 was decreased from 21% to 9% for 90 minutes followed by reoxygenation at 21% for 120 minutes. The abdomen was closed and the animals were allowed to recover. After 24 hours the mesenteric lymph nodes (MLNs), spleen, and liver were harvested for bacterial determination and the ileum and jejunum for histological evaluation. Group II (n = 7) was treated the same as group I with the FIO2 maintained at 21%. Group III (n = 3) animals were killed, without intervention, for bacterial analysis. In group I, the systemic PO2 decreased by 75%, SMV PO2 decreased by 64%, and oxygen delivery to the small bowel decreased by 80% in comparison with group II. The mean arterial pressure and cardiac output were not significantly different between group I and group II; however, the mucosal blood flow was decreased by 60% (P less than .001) in group I. Arterial and SMV blood lactic acid levels were unchanged in group I in comparison with group II, suggesting that anaerobic metabolism was not initiated in the splanchnic circulation during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403562 TI - Recognition of recurrent gastroesophageal reflux following antireflux surgery in the neurologically disabled child: high index of suspicion and definitive evaluation. AB - Multiple symptoms suggestive of gastroesophageal reflux (GER) developed in 181 of 240 children (75%) with profound neurological impairment (NI) following operative management of GER. Diagnostic testing was performed in 102 children, 56% of patients with symptoms. Recurrent GER was evident on one or more diagnostic studies in 46% of children evaluated. Significant differences (P less than .05) were found in the testing protocols of children with studies positive for GER and those individuals with negative tests. Children with study-documented recurrent GER: (1) had testing conducted at a more remote time postoperatively; (2) received a greater number of total tests; (3) were evaluated by more than one type of diagnostic test; and (4) underwent upper endoscopy and pH monitoring more frequently. No single clinical symptom was predictive of study-documented recurrent GER. These results suggest that recognition of recurrent GER after an antireflux operation in a child with profound NI requires a high index of suspicion. Definitive evaluation of children with postoperative symptoms demands repeated testing over time and the use of more than one type of diagnostic test. A contrast study should be used to evaluate the mechanical properties of the fundoplication and esophagoscopy and/or esophageal pH monitoring to assess the physiological control of GER. PMID- 1403563 TI - Quantitative and qualitative analysis of the extracellular matrix protein, laminin, in Hirschsprung's disease. AB - Previous immunohistochemical studies have shown an abnormal distribution of extracellular matrix (ECM) proteins, including laminin, in the smooth muscle layer of muscularis externa in Hirschsprung's disease (HD) bowel. These findings supported the hypothesis that an abnormal ECM microenvironment may be responsible for the failure of migration and/or development of the neural crest cells in the gut in HD. In order to determine the cause of the abnormality in laminin distribution, solid-phase enzyme-linked immunosorbent assays and immunoblots were used to quantitate the ECM protein laminin and characterize its subunits, respectively, in extracts of the dissected smooth muscle layer of the muscularis externa. In the aganglionic bowel, laminin (median concentration, 32.4 ng/mg of tissue) was found to be present in significantly greater quantity than in both the normoganglionic bowel of the same specimen (median, 17.2 ng/mg, P less than or equal to .05) and the normal bowel of age-matched controls (median, 9.7 ng/mg, P less than or equal to .05). Laminin concentration was also found to be significantly higher in normoganglionic HD bowel (median, 17.2 ng/mg) than in age matched control specimens (median, 10.8 ng/mg, P less than or equal to .05). No difference was observed in the subunit composition of laminin in HD and control extracts analysed by immunoblot after polyacrylamide gel electrophoresis. This study demonstrates a quantitative abnormality of laminin in the bowel in HD, supporting the hypothesis that "abnormal microenvironment" may have a role in the pathogenesis of HD. PMID- 1403564 TI - Pulmonary growth and remodeling in infants with high-risk congenital diaphragmatic hernia. AB - Infants born with congenital diaphragmatic hernia (CDH) have pulmonary hypoplasia, but the pattern of postnatal growth in these lungs has not been documented. The lungs of 21 children dying with CDH were analyzed to determine how the pulmonary morphology changed with age. The patients were stratified into three age groups for ANOVA analysis (less than 8 days, 8 to 21 days, greater than 21 days). Morphometric techniques previously described were used. Lung volume and weight as well as pulmonary artery length and diameter increased with age (P = .04), whereas the number of airway generations was similar for each group. Radial alveolar number also increased, particularly in the contralateral lung (P = .02). The percentage of intraacinar artery muscularization decreased with age (P = .02), while larger intraacinar arteries showed a nonmuscular structure, again particularly in the contralateral lung (P = .004). It is concluded that: (1) significant lung growth does occur postnatally at the alveolar level after CDH repair; and (2) there is postnatal vascular remodelling resulting in larger and less muscular arteries. These changes should contribute to a decrease in pulmonary arterial hypertension over time. However, the time period over which these changes occur exceeds the current limitations of invasive support measures such as extracorporeal membrane oxygenation. Elucidation of the factors responsible for this growth could result in new therapeutic strategies to enhance or accelerate postnatal pulmonary development in infants with CDH. PMID- 1403565 TI - Lessons to be learned. PMID- 1403566 TI - The challenge of transferring responsibility for diabetes management from parent to child. AB - To emancipate from their parents, children and adolescents with diabetes eventually must assume responsibility for self-care. The challenge that parents and health care professionals face is deciding when and how to transfer this responsibility from parent to child. Inappropriate transfer of self-care responsibility can precipitate poor metabolic control and strain parent-child relationships. By planning the gradual transfer of this responsibility based on children's cognitive abilities, maturity level, demonstrated self-care skills, and family environment factors, health care providers can minimize these problems. PMID- 1403567 TI - Relationships between parental ratings of infant temperament, risk status, and delivery method. AB - One hundred forty parents rated the temperament of their infants between the ages of 4 and 8 months. Analyses of the data examined the relationships between temperament and infant risk status (high or low), delivery method (vaginal or cesarean section), and the combined effects of infant risk status and delivery method. Although high-risk and low-risk infants were similar on the easy difficult profile ratings of the revised infant temperament questionnaire, high risk infants were rated more adaptable and more positive in mood than were the low-risk infants. Low-risk infants delivered by cesarean section were rated less optimally on three of the temperament factor scores, including withdrawal, mood, and adaptability. Interpretations of these findings are discussed and suggestions are offered for nurse practitioners and their provision of pediatric care to infants and their families. PMID- 1403568 TI - Negotiating with clinical agencies for nurse practitioner student experiences. AB - Selecting appropriate agencies and preceptors for pediatric nurse practitioner (PNP) students is vital for an optimal clinical educational experience. Agencies that are committed to the role of the nurse practitioner are usually willing to teach students. This article explores the process of negotiating clinical placement for PNP students. Those PNPs who wish to serve as preceptors may also benefit from this information. PMID- 1403569 TI - Implementation of "Open Airways" as an educational intervention for children with asthma in an HMO. AB - This article describes the adaptation and implementation of an existing pediatric asthma-management educational program, Open Airways, for members of a large group practice health maintenance organization. Seventy-four children ages 4 to 14 years and their families were randomized into one of seven class cohorts as part of a larger study of pediatric asthma management. The Open Airways program was modified to increase the emphasis on behavioral change and medication information and to reflect the different sociodemographic makeup of the population, compared with that for which the program was developed. Of the 74 families, 62 attended at least one class, and 47 of these attended five or more classes. Evaluations after classes suggest an increase in parental confidence in managing their child's asthma and an earlier use of medications. Health care providers may be able to adapt similar programs for successful use with their populations. PMID- 1403570 TI - School injuries: what we know, what we need. AB - Schools are the site of a substantial number of unintentional injuries each year. Current knowledge regarding the study of causes and implications of school injury is summarized in a review of the research literature. A discussion of future investigations and better management of school injuries focuses on research issues, practical management, and nursing concerns. Operational definitions and reporting mechanisms are emphasized as research needs. Practical management and nursing concerns include routine reporting, student supervision, treatment of injuries, communication with parents, and legal (liability) responsibilities. PMID- 1403571 TI - Physiologic sequelae of prematurity: the nurse practitioner's role. Part VIII. Neurologic conditions. AB - Advances in neonatal care enable smaller and sicker babies to survive. These babies are at increased risk for long-term neurologic sequelae: intraventricular hemorrhage, hydrocephalus, and seizures. This article, the eighth in a series, deals with the follow-up of premature infants with these sequelae, including recognition of shunt infections and failure, recognition and treatment of seizures, and immunization of preterm infants with neurologic problems. PMID- 1403572 TI - Alcohol use by children. PMID- 1403573 TI - Breast masses in adolescent girls. PMID- 1403574 TI - Standards for pediatric immunization practice. PMID- 1403575 TI - Hepatitis B resources review. PMID- 1403576 TI - Modulation of human gingival fibroblast cell metabolism by methyl mercaptan. AB - Methyl mercaptan (CH3SH) is a malodorous compound whose levels are elevated in mouth and crevicular air of individuals with active periodontal disease. Since it may play a role in the disease process, its effects were evaluated using human gingival fibroblast cultures and viable porcine unkeratinized oral mucosal tissue sections. Results showed that the protein content of CH3SH-exposed cell cultures pulsed with [14C]-labelled glycine and proline was decreased by approximately 25%. Furthermore, this deleterious effect was irreversible in test cultures subsequently incubated for 24 h in a control 95% air/5% CO2 mercaptan-free environment. The supporting slab-gel electrophoresis profiles yielded evidence that exposure to CH3SH caused an alteration in collagen metabolism and a pooling of Type I procollagens. In addition, DNA synthesis was suppressed in CH3SH exposed cultures by 44.1% at the 24 to 26 h peak of DNA synthesis. This is a true inhibition and not a shift in peak of maximum DNA synthesis as the shape and location of time-course curves of control and test systems is very similar. Proline transport study using [14C]-proline indicated a reduction in proline transport in the range of 40 to 50% in cultures exposed for 24 to 30 h to CH3SH. Significantly even 15 min exposure to 6.7 ng CH3SH/ml of incubating atmosphere suppressed proline transport by approximately 24%. This indicates that even brief exposure to low concentrations of CH3SH has a significant adverse effect on proline transport. Fluorescent staining of tissue sections exposed to mercaptan indicated that the agent elevated the number of cells stained with vital dye.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403577 TI - Analysis of chondroitin sulfate isomers in the periodontium of the monkey using high-performance liquid chromatography. AB - Glycosaminoglycan (GAG) was extracted from monkey periodontium, consisting of gingiva, periodontal ligament, alveolar bone and cementum, and from dental pulp and dentin by digestion with Pronase E. Unsaturated disaccharide isomers formed by chondroitinase AC digestion from chondroitin sulfate were labeled with dansylhydrazine and analyzed by high-performance liquid chromatography. These tissues showed different molar ratios of the unsaturated chondroitin sulfate disaccharides. The ratio of delta Di-4S to delta Di-6S was lowest in the dental pulp, followed by the gingiva, periodontal ligament, dentin, alveolar bone, and cementum, in that order. It was greater in the calcified than in the uncalcified tissues. PMID- 1403578 TI - Platelet-derived growth factor reduces the inhibitory effects of lipopolysaccharide on gingival fibroblast proliferation. AB - Lipopolysaccharide from a variety of bacterial sources is known to inhibit gingival fibroblast proliferation and synthetic activity and has been implicated in the pathogenesis of periodontal inflammation. However, it may be involved not only in pathogenesis but also be responsible for delayed wound healing following periodontal therapy. The aim of this investigation was to determine whether the inhibitory effect of LPS on gingival fibroblast proliferation could be reversed by growth factors. Human gingival fibroblasts were cultured in the presence of varying concentrations of platelet-derived growth factor (PDGF) or Salmonella enteritidis LPS to determine the optimal concentrations for stimulation and inhibition of proliferation respectively. The effect of PDGF on LPS inhibition of fibroblast proliferation was studied by combining PDGF and LPS together at the outset of the experimental period or adding PDGF to cells which had been previously primed with LPS. Cell proliferation was monitored by incorporation of 3H-thymidine into precipitable DNA. The results indicated that maximal inhibition of fibroblast proliferation was obtained with 50 micrograms/ml LPS and maximal stimulation of proliferation with 5 ng/ml PDGF. PDGF was found to restore the proliferative activity of the cells exposed to LPS to approximately 60% of their control counterparts. A similar value was obtained for cultures exposed to PDGF after an extended priming period of LPS exposure. Subtle differences were noted in the time taken for cells to complete their cell cycle in the various culture conditions and this may reflect variations in subpopulations of cells in their response to various mitogenic stimuli. Overall the results indicate that PDGF has the capacity to significantly negate and reverse the inhibitory effects of LPS on human gingival fibroblast proliferation. PMID- 1403579 TI - Inhibition of human endothelial cell proliferation in vitro in response to n butyrate and propionate. AB - The study aimed to investigate the effects of n-butyrate and propionate on the proliferation and viability of human endothelial cells in culture. Proliferation was assessed by a 24-hour bromodeoxyuridine pulse labelling and immunoperoxidase method and viability was assessed by a colorimetric viability (MTT) assay. Endothelial cells were isolated from human umbilical vein by collagenase digestion. Experiments were performed on 96-well plates and cultures were exposed to different concentrations of n-butyrate and propionate for 2 days. n-butyrate and propionate caused significant reductions in the proliferation of endothelial cells at concentrations of 1.25 mM and 10 mM respectively (p less than 0.05); the reduction in proliferation was dose-dependent for both agents. n-butyrate was a more potent inhibitor of proliferation than propionate. However, there were no significant effects on the viability of the cells with both agents up to the highest concentrations tested (25 mM). The data indicate that n-butyrate and propionate inhibit endothelial cell proliferation which may contribute to the pathogenic effects of dental plaque in periodontal disease. PMID- 1403580 TI - Longitudinal monitoring of humoral antibody in subjects with destructive periodontal diseases. AB - Fifty-one subjects (16-61 years old) with evidence of prior destructive periodontal disease were monitored clinically and immunologically at bi-monthly intervals for up to 5 yr. Periodontal disease activity, determined as new attachment loss, was detected in 33 of these subjects. Only 4 of 51 subjects failed to show an elevated serum antibody level to any of the 18 subgingival species tested. The antibody level threshold established for periodontally healthy subjects was exceeded most often in diseased subjects with serum antibody to Actinobacillus sp., P. gingivalis, E. corrodens, C. concisus, F. nucleatum and P. intermedia in that order. In general, most serum antibody levels to subgingival species remained relatively consistent for periods as long as 5 yr. However, major increases and decreases in antibody could be detected to at most one or two species in individual subjects. In addition, prolonged, steady increases and decreases in antibody to specific species could be detected in certain subjects. These findings suggest that major changes occurring in serum antibody may reflect fluctuations in the nature of the infection. Differences were observed in the antibody level to specific species when subjects were divided into subsets on the basis of clinical criteria. These included high levels of antibody to A. actinomycetemcomitans Y4 in LJP and RPP subjects and to A. actinomycetemcomitans 29523 in LJP and GJP subjects. PMID- 1403581 TI - A preliminary evaluation of the use of a redox agent in the treatment of chronic periodontitis. AB - A small-scale clinical trial was carried out to evaluate the effect of a redox agent, methylene blue, on microbiological and clinical indices of chronic periodontitis. Methylene blue was applied subgingivally on a daily basis for 7 d to 25 test sites in 7 patients and the sites evaluated clinically and microbiologically for up to 14 d: 25 control sites in the same patients received sterile water. The test sites showed statistically significant differences from the control sites in terms of changes in a number of clinical and microbiological indices. In the test sites the proportions of anaerobes, Gram-negative anaerobes, spirochetes and motile bacteria decreased, as did the crevicular fluid flow, while the proportions of facultative anaerobes and cocci increased. These changes are indicative of a shift towards periodontal health. No significant differences were observed between the test and control sites in terms of bleeding on probing or pocket depth. The encouraging results of this preliminary study suggest that the use of redox agents in the treatment of chronic periodontitis warrants further investigation. PMID- 1403582 TI - Phospholipase A2 in rat gingival tissue. AB - Phospholipase A2 (PLA2) is a proinflammatory enzyme in the synovial fluids of all -and sera of some--patients with rheumatoid arthritis. Due to the similarities in pathogenesis between rheumatoid arthritis and periodontitis, we sought to study the enzymatic properties of PLA2 in periodontal tissue. In this study, we demonstrated PLA2 activity in rat gingival tissue, about 80% of which was present in the cytosolic fraction. We characterized the cytosolic PLA2 enzyme with respect to substrate specificity, sensitivity to detergent, Ca2+ ion dependency and optimum pH. We found that phosphatidylethanolamine, rather than phosphatidylcholine, was the preferred substrate, the Ca2+ ion was essential for the expression of PLA2 activity, the enzyme was active over a broad pH range, with the optimum at pH 9.0, and sodium-deoxycholate inhibited the enzyme activity strongly in a concentration-dependent manner. These results are consistent with those which have been obtained with synovial fluid PLA2 and suggest that gingival PLA2 may be involved in the pathogenic processes of gingivitis and periodontitis. PMID- 1403583 TI - Micropuncture measurements of interstitial fluid pressure in normal and inflamed gingiva in rats. AB - Interstitial fluid pressure (IFP) in normal and inflamed gingiva of rats was measured by sharpened glass capillaries (diameter 2-4 microns) connected to a servocontrolled counterpressure system ad modum Wiederhielm. Gingival inflammation was induced by a steel ligature placed unilaterally around the first maxillary molar. After 8 weeks, the ligature was removed and measurements of IFP in normal and experimentally inflamed gingiva were made by puncture through the intact oral epithelium. Average IFP on the control side was 3.5 mm Hg in free, and 7.4 mm Hg in attached gingiva. Compared to the control side, IFP on the experimental inflamed side was elevated significantly (p less than 0.05) both in free and attached gingiva. In the ligated inflamed side IFP in free gingiva averaged 6.7 mm Hg, whereas in attached gingiva it showed a mean value of 10.4 mm Hg. Histological examinations showed a dense infiltrate of inflammatory cells in the connective tissue, while the contralateral control side showed normal features of epithelial and connective tissue. The present finding of increased IFP in the inflamed gingiva may in theory contribute to augmented crevicular fluid flow during inflammation. PMID- 1403584 TI - Flurbiprofen effect on gingival crevicular fluid prostaglandin and thromboxane levels in humans. PMID- 1403585 TI - Gingival crevicular fluid gelatinase and its relationship to periodontal disease in human subjects. AB - Collagenolytic enzymes released by neutrophils are associated with the destruction of periodontium in periodontal diseases. Measurement of these enzymes in gingival crevicular fluid (GCF) could be used to test for periodontal diseases and thereby simplify diagnosis. To test this hypothesis, gelatinase (MMP-9) was analyzed in GCF samples with a simple assay system. GCF was collected by a mouthrinse method from 10 patients with gingivitis (G); 10 well-treated and maintained periodontitis patients (TP) without detectable loss of attachment; and 9 patients with recurrent loss of periodontal attachment (greater than 2 mm) and/or abscess formation (RP). Clinical measurements including tooth mobility (MOB) and gingival attachment level (GAL) were made monthly for a maximum of 10 months. Active and latent forms of gelatinase were measured by a functional assay using gelatin substrate-gel enzymography and the activities were quantified by laser densitometry. Reproducibility analysis demonstrated that the assay (inter gel, inter-assay, inter-scan) and diurnal variations were small compared to biological variation. The presence of active gelatinase was detected in 97.8% of TP samples, 86.4% of RP samples, but in only 11.4% of G samples. In addition, the mean active gelatinase activity was found to be significantly higher (p less than 0.001) in the RP (71,006 U) than the TP (43,814 U) groups, both of which were higher (p less than 0.001) than the G group (2824 U). During periods of attachment loss, samples from the RP group exhibited a 2-fold increase of mean active gelatinase activity (129,414 U).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403586 TI - The effect of titanium implant abutment surface irregularities on plaque accumulation in vivo. AB - The purpose of this study was 2-fold to: 1) evaluate in vitro the surface texture of titanium implant abutments after exposure to plastic scalers, an air-powder abrasive system, rubber cup polishing with flour of pumice, and untreated control abutments; and 2) compare plaque accumulation in humans on abutments treated with the above methods. In part I, 5.5 mm abutments were instrumented for 30 seconds per 90 degrees segment with the respective methods. The surface character was compared to untreated controls using SEM at 260X magnification. The control abutments revealed prominent milling marks and small pits; plastic scalers slightly smoothed the milling marks and created microscratches; the air-powder abrasive largely obliterated the milling marks and caused some surface pitting; the rubber cup with flour of pumice removed the milling marks and created a smooth swirl pattern. None of the instrumentation appeared to roughen the surface. In the clinical experiment (part II), four abutments, one of each type, were placed in 12 patients for a period of 7 days, during which the patients performed no oral hygiene. At the end of 7 days, the abutments were retrieved and processed for SEM. A digitizer and software program were used to determine the percent of total abutment surface area covered by plaque. The demarcation of supragingival and subgingival plaque was well delineated. The total mean percent surface area of plaque ranged from 52.06% for the air-powder abrasive to 55.29% for the plastic scalers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403587 TI - Effect of subgingival irrigation with chlorhexidine during ultrasonic scaling. AB - This study examines the effect of a chlorhexidine irrigant during ultrasonic scaling and root planning and compares clinical results with those obtained using a water irrigant. The irrigant was delivered either through a conventional or a recently-introduced ultrasonic scaler, which allows the irrigant solution to be passed through the inside of the scaler tip. The study utilizes a split-mouth design and contrasts the effectiveness of both instruments in improving periodontal health, as measured by standard clinical indices. A preliminary investigation of patient tolerance to treatment performed throughout the clinical trial was also undertaken. Statistical analysis at the 3 and 6 month post treatment stage revealed no significant differences between the 4 experimental groups in respect of probing attachment levels (P > 0.5), bleeding index (P > 0.1), or plaque index (P > 0.05). Clinical attachment gain assessed by probing ranged from 0.6 to 0.9 mm. Chlorhexidine increased patient tolerance in 77% of cases and the new model ultrasonic scaler was favored over the traditional model in 70% of cases. The magnitude of the tolerance differences was however not statistically significant. The possible potential of the new scaler and of chlorhexidine as an irrigant to reduce patient discomfort is worthy of further investigation than was possible in this study. PMID- 1403588 TI - Serum levels of tetracycline during treatment with tetracycline-containing fibers. AB - Four adult patients with at least 8 teeth that had attachment loss of 5 to 10 mm which bled on probing were included in this study. Polymeric tetracycline (TCN) containing fibers were placed and left in the pockets for a period of 10 days. Plasma samples were collected at baseline, 1 hour, 3 hours, 3 days, and 10 days after fiber placement. The mean length of fiber used averaged 187 cm with a range of 160 to 222 cm. The maximum TCN dose per patient averaged 105 mg with a range of 91 to 126 mg producing no detectable serum level greater than 0.1 micrograms/ml. This level was found in 3 of the 4 subjects at 3 hours after fiber placement and in 1 subject at 3 days after fiber placement. Transient and insignificant levels of TCN became available systemically shortly after the placement of multiple fibers. The dose of TCN in each patient was well tolerated and was not associated with any serious adverse effects. PMID- 1403589 TI - Efficacy of preprocedural rinsing with an antiseptic in reducing viable bacteria in dental aerosols. AB - This double-blind, controlled, cross-over, clinical study evaluated the effect of preprocedural rinsing with an antiseptic mouthrinse on the level of recoverable viable bacteria in an aerosol generated during a typical dental procedure. Eighteen subjects participated. Following 24 hours of abstention from all oral hygiene procedures, subjects received a 10-minute ultrasonic scaling of a randomly selected one-half of their mouth which served as the unrinsed control. They were then randomly assigned either antiseptic mouthwash or a control rinse and rinsed with 20 ml for 30 seconds, after which the remaining half mouth (experimental side) was scaled ultrasonically for 10 minutes. During each 10 minute scaling period aerosolized bacteria were collected on a sterile filter using a modified vacuum air-sampling device. Microbes captured on the sterile filter were quantitated by overlaying the filters onto trypticase soy agar, incubating the filters aerobically at 37 degrees C for 24 to 72 hours, and counting the resulting colony forming units (CFU). Preliminary experiments had confirmed that neither the collection method nor residual antiseptic mouthwash in the aerosol adversely affected the number of viable bacteria recovered from the filter. Rinsing with the antiseptic mouthwash produced a 94.1% reduction in recoverable CFUs compared to the non-rinsed control, while the control rinse produced a 33.9% reduction. The difference between the mouthwash and control was statistically significant (P < .001). This study indicates that preprocedural rinsing with an antiseptic mouthwash can significantly reduce the microbial content of aerosols generated during ultrasonic scaling and may have potential in office use as part of an infection control regimen. PMID- 1403590 TI - Measuring clinical attachment: reproducibility of relative measurements with an electronic probe. AB - During the past few years, improvements in detecting longitudinal changes in clinical attachment or alveolar bone density have been introduced. For example, constant-force electronic probes and computer-assisted subtraction analysis of longitudinal radiographs have been reported to be more sensitive and reproducible in detecting changes in clinical attachment or alveolar bone density, respectively. Use of these new technologies requires that sources of measurement error be identified and their contribution quantified. This study investigated the reproducibility of a constant-force electronic probe in a careful clinical setting. Measurements were performed from individually fabricated acrylic stents. Three groups of subjects were selected for the study: 10 adults without oral disease, 10 adults with gingivitis, and 10 adults with moderate periodontitis. Four probing designs were employed to investigate the reproducibility of the probe. In design A, the probe tip was left in the sulcus between successive probings. In design B, the probe tip was removed from the gingival margin between probings but the next probing followed immediately. In design C, successive whole mouth probings were interrupted by a 5-minute interval and a mouth rinse. In design D there was a 4-week interval between each successive probing. Three measurements were taken at each site for each design. The main purpose of this study was to identify variance components in the attachment level variation. The maximum probing error standard deviation ranged from 0.2 to 0.3 mm depending on the periodontal health of the subject. This level of variation is considerably smaller than that found in most previous studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403591 TI - The effect of a number of commercial mouthrinses compared with toothpaste on plaque regrowth. AB - Mouthwashes are frequently used as adjuncts to oral hygiene. However, for some products there is little supportive evidence that rinses provide greater benefits than plain water or additional benefits to the plaque inhibitory action provided by toothpaste. This study was a single blind, randomized, cross-over design in which 6 rinses were compared for inhibitory action against plaque regrowth. The formulations were a cetylpyridinium chloride rinse, a prebrushing detergent rinse, a peroxyborate rinse a toothpaste slurry rinse, a chlorhexidine rinse, and a saline rinse. From a zero baseline, plaque regrowth at day 5 was significantly reduced by chlorhexidine compared to peroxyborate; and, in turn, significantly reduced by peroxyborate compared to the other rinses. There were no significant differences between saline or a toothpaste slurry and the cetylpyridinium chloride or prebrushing rinse products. The findings would appear pertinent to the value of the respective rinses as adjuncts to oral hygiene. PMID- 1403592 TI - The relationship between reduction in periodontal inflammation and diabetes control: a report of 9 cases. AB - The established correlation between diabetes and periodontal diseases and the increasing prevalence of Type II diabetes in the general population indicate that dental practitioners will probably treat an increasing number of diabetic patients. Despite the fact that there is little scientific evidence to support the concept, it has been generally accepted that treatment for periodontal disease in diabetic patients may reduce insulin requirements and improve metabolic balance. However, to date no one has evaluated the effects of periodontal therapy on the metabolic state of the poorly-controlled diabetic patient. The purpose of this pilot study was to evaluate the effect of controlling gingival inflammation on blood glucose levels as determined by glycosylation of hemoglobin and albumin. PMID- 1403593 TI - Tissue concentration and localization of tetracycline following site-specific tetracycline fiber therapy. AB - The primary objective of this study was to evaluate the concentration and location of tetracycline hydrochloride in tissue adjacent to periodontal pockets treated with a tetracycline impregnated fiber. A secondary objective was to determine if the presurgical placement of fibers had any adverse effects on healing following periodontal surgery. The study population consisted of 10 patients with at least 2 pockets in both maxillary quadrants of > or = 5 mm in depth and exhibiting bleeding on probing. After an initial scaling and root planing, placebo or tetracycline fibers were randomly assigned by quadrant to 2 non-adjacent pockets. Fibers were removed at the time of surgery; i.e., day 8, and periodontal surgery was performed utilizing a flap incision that allowed biopsy of 1 interdental papilla from each of the 2 test sites in each quadrant. One biopsy was analyzed for tetracycline concentrations by high performance liquid chromatography (HPLC). The second biopsy was examined by both light and ultraviolet fluorescence microscopy to determine the location of residual tetracycline and the intensity of inflammatory cell infiltrates. Results showed that the tissue concentration of the antibiotic in tetracycline treated sites was 64.4 +/- 7.01 ng/mg (ng of tetracycline/mg tissue weight) which corresponds to 43 micrograms of tetracycline and was below levels of accurate measurement in placebo treated sites. Tetracycline tissue concentrations corresponded to the ultraviolet fluorescence microscopy with a Pearson correlation coefficient of r = 0.92. Tetracycline fluorescence was noted in the soft tissue wall ranging from 1 to 20 microns.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403594 TI - Psoriasis-associated periodontitis: a case report. AB - Psoriasis with oral manifestations is rarely seen. It has been reported in the past either as an oral manifestation of this skin disease or lichen planus accompanying psoriasis. Very few periodontal lesions associated with dermatologic psoriasis have been reported in the literature. This report describes a case of psoriasis in which exacerbation of the cutaneous disease was accompanied by gingival epithelial changes and periodontal bursts, together with a report on the light microscopy of biopsies from periodontal lesions. PMID- 1403595 TI - The dimensionality of Type A behavior within a stressful work simulation. AB - The present study was conducted to examine the dimensionality of overt Type A behaviors elicited in a simulated stressful work environment. University students played a managerial role while being subjected to time and work-load pressures, and completed the Survey of Work Styles (SWS; Jackson & Gray, 1989). Eighteen behaviors, coded by two raters based on audiovisual recordings, yielded relatively high interrater reliabilities. Principal components analysis revealed four primary factors: Hurriedness, Irritability, Tension of the Lower Extremities, and Restlessness. These factors contribute to an understanding of Type A behavior in that they are the first to be derived from a purely observational approach rather than a combination of observational and self-report methods. Consistent with previous research, differential correlations between the factors and the SWS subscales supported a multi-dimensional interpretation of the Type A behavior pattern. Present findings are compared to those of previous studies of Type A dimensionality. PMID- 1403596 TI - The personality of young adult couples and wives' work patterns. AB - The influence of personality in 63 couples at the time of family formation on wives' work patterns 15 years later was examined in variable-centered and person/couple-centered ways. Four factor dimensions on the Adjective Check List assessed personality. Work patterns were assessed with measures of type, amount, and status of work and with schematic work narratives describing characters and plots abstracted from wives' mid-life data. Hierarchical regression analyses showed individuality of husbands to affect work outcomes after wives' college-age goals, their young adult personality, and the duration of marriages were taken into account. Conjoint high-low patterns of individuality in 34 couples were associated with different schematic work stories. These stories show distinctive personality and relational correlates at age 27. They flesh out and qualify hypotheses that individualistic partners would be open to women's careers and would show revealing strategies of combining self- and other interests in the transition to parenthood. PMID- 1403597 TI - Stability of self-esteem: assessment, correlates, and excuse making. AB - We examined stability and level of self-esteem as predictors of excuse making; the extent to which self-ratings of stability are related to a statistical index of self-esteem stability; and the relations between stability and certainty of self-esteem and a variety of other psychological constructs. Regarding excuse making, our findings indicated that for high self-esteem individuals, instability was related to greater excuse making following success, but not following failure. However, for low self-esteem individuals, instability was related to greater excuse making following failure, but not following success. Other findings indicated that self-ratings of stability were only minimally related to a statistical measure of stability based on repeated assessments of self-esteem obtained in naturalistic contexts. Finally, stability of self-esteem was not significantly correlated with certainty of self-esteem. In addition, the pattern of correlations that emerged between certainty and other constructs suggested that uncertainty reflects the phenomenal experience of a tenuous self-view. On the other hand, stability of self-esteem appears to reflect the extent to which one's self-view is malleable, which may not be completely available to conscious awareness. Our discussion focuses on the nature of self-esteem stability and the roles of stability and level of self-esteem in reactions to evaluative events. PMID- 1403598 TI - [Ionizing treatment of food]. AB - After a description of the principles of the radiation treatment of food, the main applications in food industry are listed. Then, the status on possible identification methods for irradiated foodstuffs is described, with a special view on the coordinated action of the Community Bureau of Reference (CEC). PMID- 1403599 TI - Influence of physico-chemical parameters on the release kinetics of ketoprofen from Poly(HEMA) crosslinked microspheres. AB - This report analyses the release of Ketoprofen from Poly(HEMA) microspheres crosslinked with EGDMA at different crosslinking ratios and loaded by soaking in saturated solutions of the drug. Release appears to be influenced by the dissolution of Ketoprofen in the hydrogel and it is strictly correlated with the diffusibility of the drug in the gelled matrix. The release rate of the drug in the hydrogel rises with the increase in the diffusional conductance and the release kinetics approaches zero order particularly at the higher values of the diffusional conductance. PMID- 1403600 TI - [Clinical aspects of receptors; from animal models to physiopathological concepts. Experience with fenfluramine]. AB - The fenfluramine racemate belongs to a new therapeutic class of molecules acting on food intake, without psychostimulant or addictive potential. This molecule was extensively studied in the treatment of obesity and its action was better understood by studying the dextrogyre and levogyre enantiomers. New methods allowed to show that dexfenfluramine (the dextrogyre isomer) worked through a serotoninergic activity which was responsible for the effect on food intake and disorders of eating behavior. New pharmacological concepts have emerged by using this molecule and new animal models, nearer to human pathology, were found (stress induced eating, carbohydrate selection...). Molecular Biology and Neurosciences have already led to a better knowledge of the central mechanism of action of the molecule by describing its effect on receptors and binding sites; however a lot of other concepts remain to be discovered. PMID- 1403602 TI - [Reactions and interactions of drugs]. PMID- 1403601 TI - [Mechanism of action of hypolipemic drugs]. AB - Hypolipemic drugs decrease the plasmatic concentrations of atherogenic lipoproteins, especially LDL. Two main drug families are used: fibrates and inhibitors of HMG CoA reductase. Fibrates act essentially as an activator of lipoprotein lipase and by increasing the catabolism of triglyceride rich lipoproteins. Further, they have a slight and non specific inhibitory effect on HMG CoA reductase activity, while, the new drug family of "statines" have a high, specific inhibitory effect on this essential enzyme of the cholesterol synthesis pathway. This enzymatic inhibition decreases the cholesterol synthesis and increases the activity of the hepatic LDL receptors, which are in charge of LDL elimination from the body. Resins entrap biliary salts and increase the cholesterol loss in feces and induce an over expression of the LDL receptors of the hepatocytes. Probucol inhibits atherogenesis by decreasing both LDL and HDL cholesterol and delaying LDL oxidative processing which is now believed to be one of the major factors of atherogenicity. PMID- 1403603 TI - Comparative effects of chloroflavone congeners as inducers of hepatic microsomal monooxygenases in rats. AB - The inductive effects of pretreatment with 10 synthetic chloroflavone isomers and congeners (80 mg/kg/d for 3 d, i.p.) on hepatic microsomal monooxygenases were examined with male Wistar rats. All chloroflavone congeners, except 3' chloroflavone (CF), significantly increased (1.2- to 2-fold) the content of total cytochrome P-450 (P-450s) in microsomes. The effects of these congeners were evaluated based on the activities of microsomal aminopyrine N-demethylase, aniline hydroxylase and scoparone (6,7-dimethoxycoumarin) O-demethylase, and the CO difference spectrum and sodium dodecyl sulfate-gel electrophoretogram of cytochrome P-450s. The results were compared with those of phenobarbital (PB), 3 methylcholanthrene (MC) and PB plus MC. Based mainly on effects on the CO difference spectrum and ratio of the two O-demethylase activities of scoparone, 2'-CF and 2',4'-dichloroflavone (DCF) were categorized as the PB-type, 4'-CF and 6,8-DCF as the MC-type, 3',6-DCF and 3',5',6-trichloroflavone as weak MC-type, and 6-CF and 2',6-DCF as mixed (PB plus MC)-type inducers. A comparison of chloroflavone isomers and congeners indicated that (1) the presence of the 2' chloro substituent of the flavone system is a minimal requirement for exhibiting the PB-type effect, (2) the absence of the 2'-chloro substituent is possibly that for exhibiting the MC-type effect and (3) the induction potencies by individual chloroflavone congeners may not be related to the degrees of chlorination. PMID- 1403604 TI - The biological fate of sodium prasterone sulfate after vaginal administration. I. Absorption and excretion in rats. AB - The absorption and excretion of sodium prasterone sulfate (PS) (sodium dehydroepiandrosterone sulfate) were studied in rats after vaginal administration of 14C-PS. In late pregnant rats, maximum plasma level (Cmax) appeared at 2-4 h after dosing and both Cmax and the area under the plasma concentration-time curve (AUC) increased proportionally with increased dose up to 4.0 mg/kg. The radioactivity administered was almost completely recovered from urine and feces during a 72 h postdosing period. The percentages of radioactivity excreted in urine and feces were 58% and 40% of the dose, respectively. The biliary excretion was 46% of the dose within 48 h and about half of the radioactive biliary excreta entered the enterohepatic circulation system. The vaginal absorption of PS was markedly affected by the estrous cycle stage and the progress of pregnancy. The vaginal absorption of PS was predominant at metestrus and diestrus and during late pregnancy. PMID- 1403605 TI - YM-14673, a new thyrotropin-releasing hormone analog, augments long-term potentiation in the mossy fiber-CA3 system of guinea pig hippocampal slices. AB - Effects of a new thyrotropin-releasing hormone (TRH) analog, N alpha-[[(S)-4-oxo 2-azetidinyl]carbonyl]L-histidyl-L-prolinamide dihydrate (YM-14673), which improves experimentally induced memory dysfunction, on long-term potentiation (LTP) in the mossy fiber-CA3 system, were investigated using guinea pig hippocampal slices. At concentrations of 10(-7) M and 10(-6) M, YM-14673 significantly augmented LTP in a concentration dependent manner. The magnitude of effect of 10(-6) M YM-14673 was similar to that of 10(-6) M TRH. As LTP in the hippocampus is regarded as an elementary process of memory and learning, the augmenting effect of YM-14673 on LTP in the present study may contribute to this drug's ability to remedy memory dysfunction. PMID- 1403606 TI - An application of microdialysis to drug tissue distribution study: in vivo evidence for free-ligand hypothesis and tissue binding of beta-lactam antibiotics in interstitial fluids. AB - To prove the free-ligand hypothesis for extravascular equilibration and tissue binding mechanism of beta-lactam antibiotics, the microdialysis technique has been employed for the lung, the muscle and the liver in rats. Cefminox, a cephem antibiotic, and SY5555, a new penem antibiotic, were used in the present study. During the constant infusion of each antibiotic with simultaneous infusion of antipyrine, the microdialysis studies were performed and the dialysate concentrations were determined. The dialysate concentration was extrapolated to the in vivo unbound concentration in tissue interstitial fluids (Cisf,u) according to the extrapolation method which was derived from the clearance concept. This extrapolation method incorporates the effective dialysis coefficient of a reference compound, antipyrine, which is used to correct the difference between in vivo and in vitro permeabilities of microdialysis fiber. The values of Cisf,u values for cefminox and SY5555 in the lung, muscle and liver were close to the unbound concentrations in the venous plasma leaving these organs. Furthermore, good coincidences were obtained between the unbound concentrations of SY5555 in lung and muscle interstitial fluids estimated from the total concentrations in homogenized tissues and those extrapolated by the microdialysis studies. Consequently, the present microdialysis studies provided the in vivo evidence that 1) the free-ligand hypothesis for extravascular equilibration of beta-lactam antibiotics is true, and that 2) beta-lactam antibiotics are restricted in the interstitial space in a noneliminating organ and bind only with albumin existing in this space. PMID- 1403607 TI - Coexpression of vimentin and glial fibrillary acidic protein in glial cells of the adult rat pineal gland. AB - In the present work, coexpression of vimentin (VIM) and glial fibrillary acidic protein (GFAP) is demonstrated in the glial cells of the adult rat pineal gland. Serial consecutive Epon semithin sections (0.5 microns thick) were alternately immunostained for VIM and GFAP. GFAP positive cells and processes were found in the proximal region of the pineal gland, near the pineal stalk. Most of these cells were also immunostained for VIM in adjacent semithin sections. The significance of the coexpression VIM-GFAP and the restricted location of GFAP positive cells is discussed in relation with the maturation of pineal glial cells. PMID- 1403608 TI - Paradoxical effects of melatonin on spontaneous neuronal activity in the striatum of sham-operated and pinealectomized rats. AB - The acute effects of intravenous melatonin on spontaneously active striatal neurons in sham-operated and pinealectomized rats were studied. Extracellular recordings in a total of 76 neurons showed that only 19 did not modify their spontaneous activity after melatonin injection. In sham-pinealectomized rats, neural firing decreased in most cells (80% of neurons), and increased in only 5.7% of the neurons after indole administration (100 ng/kg body weight). However, in the group of rats pinealectomized 7 days earlier, the injection of melatonin (at the same dose as above) significantly increased the excitatory response (44%), while the number of cells showing inhibitory response decreased (17%). Moreover, a small percentage (4.9%) of neurons in pinealectomized rats displayed a biphasic response (initial decrease followed by an increased firing). These results demonstrate that aMT can modulate the activity of striatal neurons, and suggest that other compounds of pineal origin (e.g., vasotocin) may change effects of aMT on basal ganglia neurons. PMID- 1403609 TI - Components of the melatonin message in the response to photoperiod of the tammar wallaby (Macropus eugenii). AB - Female tammars experiencing long-day photoperiod (LD 15:9) are in a reproductive state termed seasonal quiescence. After a change to LD 12:12, a sequence of endocrine events, dependent on a melatonin message being interpreted during the next 3 days, leads to the disappearance of a morning pulse of prolactin on day 4, and to reactivation of the quiescent corpus luteum by day 8. Elements of the message were investigated in three experiments. In experiment 1, tammars on LD 15:9 were injected with melatonin 2.5 hr before lights out on 0-5 successive days. All those receiving four or five daily injections, and six of ten receiving two or three injections, reactivated. In experiment 2, tammars on LD 15:9 were injected with melatonin or oil on 5 consecutive days to achieve a lengthening of the period of elevated melatonin from 9.0 hr to 9.5 hr, 10 hr, 10.5 hr, and 11.5 hr respectively. One of five tammars experiencing 10 hr and seven of ten experiencing the longer periods reactivated. In experiment 3, tammars on LD18:6 received melatonin 6 hr, 6 + 3 hr or 3 hr before lights out for ten successive days. Between injections the melatonin concentrations returned to basal levels. The treatments thus provided a skeletal increase in the profile of melatonin from 6 to 9 hr or 6 to 12 hr. All those treated at 6 + 3 hr reactivated and three of five treated at 6 hr only reactivated. We conclude that the tammar stores information about the change in the maximum duration of elevated melatonin experienced each night and, after three successive periods in which the duration is greater than 10.5 hr, it reactivates. Since reactivation cannot occur until completion of the third dark phase, the processing center must be active during the fourth day, prior to the abolition of the prolactin peak. PMID- 1403610 TI - Prolonged suppression of serum concentrations of melatonin in prepubertal heifers. AB - Our objective was to suppress the daily surge of melatonin in serum of prepubertal dairy heifers by manipulating intensity of light (Experiment 1) and duration of exposure to light (Experiment 2). Heifers in Experiment 1 were exposed to either 12 hr of darkness (000 lux, control), or 400, 800, or 1,200 lux of light during the last 6 hr of their usual 12-hr nocturnal period. During this 6-hr exposure to various intensities of light, melatonin concentrations were similar to their respective daytime baseline values measured under 400 lux of light, but were 62% to 82% lower than melatonin concentrations during their nocturnal surge period. Suppression of melatonin concentrations was similar between 400 and 1,200 lux of light. In Experiment 2, heifers were exposed to LD 8:16, LD 16:8, LD 20:4, or LD 24:0 photoperiods (1,200 lux) for 4 months. Throughout treatment, concentrations and durations of the melatonin surge were suppressed in the LD 24:0 group and were greatest (during the nocturnal period) in the LD 8:16 group. Concentrations of prolactin in serum were elevated in animals under long days relative to LD 8:16 treatment and respective pretreatment periods. In conclusion, continuous light at an intensity of 1,200 lux suppressed the nocturnal surge of melatonin, but increased secretion of prolactin for at least 4 months in prepubertal heifers. PMID- 1403611 TI - On the orienting value of attitudes: attitude accessibility as a determinant of an object's attraction of visual attention. AB - Four experiments tested the hypothesis that objects toward which individuals hold attitudes that are highly accessible from memory (i.e., attitude-evoking objects) are more likely to attract attention when presented in a visual display than objects involving less accessible attitudes. In Experiments 1 and 2, Ss were more likely to notice and report such attitude-evoking objects. Experiment 3 yielded evidence of incidental attention; Ss noticed attitude-evoking objects even when the task made it beneficial to ignore the objects. Experiment 4 demonstrated that inclusion of attitude-evoking objects as distractor items interfered with Ss' performance of a visual search task. Apparently, attitude-evoking stimuli attract attention automatically. Thus, accessible attitudes provide the functional benefit of orienting an individual's visual attention toward objects with potential hedonic consequences. PMID- 1403612 TI - Terror management and tolerance: does mortality salience always intensify negative reactions to others who threaten one's worldview? AB - Terror management research has shown that reminding Ss of their mortality leads to intolerance. The present research assessed whether mortality salience would lead to increased intolerance when the value of tolerance is highly accessible. In Study 1, given that liberals value tolerance more than conservatives, it was hypothesized that with mortality salience, dislike of dissimilar others would increase among conservatives but decrease among liberals. Liberal and conservative Ss were induced to think about their own mortality or a neutral topic and then were asked to evaluate 2 target persons, 1 liberal, the other conservative. Ss' evaluations of the targets supported these hypotheses. In Study 2, the value of tolerance was primed for half the Ss and, under mortality-salient or control conditions, Ss evaluated a target person who criticized the United States. Mortality salience did not lead to negative reactions to the critic when the value of tolerance was highly accessible. PMID- 1403613 TI - Marital processes predictive of later dissolution: behavior, physiology, and health. AB - Seventy-three married couples were studied in 1983 and 1987. To identify marital processes associated with dissolution, a balance theory of marriage was used to generate 1 variable for dividing couples into regulated and nonregulated groups. For studying the precursors of divorce, a "cascade" model of marital dissolution, which forms a Guttman-like scale, received preliminary support. Compared with regulated couples, nonregulated couples had (a) marital problems rated as more severe (Time 1); (b) lower marital satisfaction (Time 1 and Time 2); (c) poorer health (Time 2); (d) smaller finger pulse amplitudes (wives); (e) more negative ratings for interactions; (f) more negative emotional expression; (g) less positive emotional expression; (h) more stubbornness and withdrawal from interaction; (i) greater defensiveness; and (j) greater risk for marital dissolution (lower marital satisfaction and higher incidence of consideration of dissolution and of actual separation). PMID- 1403614 TI - Empathy: a physiological substrate. AB - The relation between empathy (defined as the ability to perceive accurately how another person is feeling) and physiology was studied in 31 Ss. Ss viewed 15-min martial interactions and used a rating dial to indicate continuously how they thought a designated spouse was feeling. Rating accuracy was determined by comparing Ss' ratings with identical self-ratings obtained previously from the target spouse. Physiological linkage between S and target was determined using bivariate time-series analyses applied to 5 autonomic and somatic measures obtained from the S during the rating task and from the target spouse during the original conversation. Accuracy of rating negative emotion was greatest when S and target evidenced high levels of physiological linkage across time. Accuracy of detecting positive emotion was related to a state of low cardiovascular around in the S, but not to physiological linkage between S and target. PMID- 1403615 TI - Accuracy in perceptions of interpersonal interactions: effects of dysphoria, friendship, and similarity. AB - Conflicting views of depressives' interpersonal accuracy were addressed in an investigation of the accuracy of mild depressives (dysphorics) across differing social contexts. Women who were either friends or strangers and who were either similar or dissimilar in level of dysphoria conversed about 3 topics: a neutral topic, their own disclosure of a personal problem, and their partner's disclosure. Dysphorics were not more accurate in general than nondysphorics. After self-disclosure, all women more accurately detected sympathy from a similar stranger. After the partner's disclosure, women also better detected the mood of a similar partner. When interacting with nondysphoric strangers, however, dysphorics underestimated their partner's sympathy toward them. Implications for cognitive and interpersonal theories of depression and for depressives' relationships are discussed. PMID- 1403616 TI - Psychosocial development in adulthood: a 22-year sequential study. AB - Data supporting the notion of adult personality stability are challenged by the present findings, in which developmental change was demonstrated using the Eriksonian-stage-based Inventory of Psychosocial Development (IPD; Constantinople, 1969). A sequential design over the ages 20-42 was used on 2 cohorts of college students and alumni originally tested in 1966 and 1976-1977 (ns in 1988 = 99 and 83, respectively), and a 3rd cohort of college students in 1988-1989 (n = 292). Results of longitudinal, cross-sectional, and sequential analyses challenged ideas about personality stability, with evidence of increasingly favorable resolutions of the early Eriksonian psychosocial stages up through the oldest age studied. There was evidence of a trend over the past decade toward less favorable resolution of ego integrity versus despair. The findings were interpreted in terms of developmental change processes during the adult years interacting with culturally based environmental effects on psychosocial development. PMID- 1403617 TI - Multiple protective and risk factors for drug use and abuse: cross-sectional and prospective findings. AB - A conceptual elaboration was developed that incorporates many risk and protective factors, and both direct and moderating (buffering) influences on drug involvement were tested. From prospective data, 14 factors related to drug use were selected and assigned empirically to either a multiple protective index (PFI) or a risk factor index (RFI). Analyses examined the relationships of the RFI, PFI, and their interaction on measures of cigarette, alcohol, cannabis, cocaine, and hard drug use cross-sectionally in late adolescence and later in young adulthood. These same variables were used to predict alcohol, cannabis, and cocaine abuse 8 years later. Vulnerability as measured by the RFI, PFI, and their interaction was highly associated with drug use in adolescence, moderately associated with certain types of drug use in young adulthood, and strongly associated with heightened drug problems in adulthood. PMID- 1403618 TI - General and specific support expectations and stress as predictors of perceived supportiveness: an experimental study. AB - Fifty-four undergraduates and their mothers participated in an experiment to evaluate hypotheses derived from a theory of perceived social support (Pierce, Sarason, & Sarason, 1990). Regression analyses indicated that the variables in the model accounted for 14.83% and 40.93%, respectively, of the variance in students' perceptions of their mothers' behavior assessed during 2 standardized laboratory situations. Unique effects were found for students' expectations for support from and conflict with their mothers in both pre- and posttask situations, although the effect of conflict was contrary to prediction in the pretask situation. Stress had an impact only in the posttask situation. Students' general expectations for support had no unique impact in either situation. Implications for the role of general and specific expectations for support and conflict, and situational factors, in theories of perceived social support are discussed. PMID- 1403619 TI - The effect of normative beliefs on anticipated emotions. AB - In 3 experiments, Ss were asked how they would or should make hypothetical decisions and how they would react emotionally to the options or outcomes. The choices were those in which departures from proposed normative models had previously been found: omission bias, status quo bias, and the person-causation effect. These effects were found in all judgments, including judgments of anticipated emotion. Arguments against the departures affected judgments of anticipated emotion as well as decisions, even though the arguments were entirely directed at the question of what should be done. In all but one study, effects of these arguments on anticipated emotion were as strong as their effects on decisions or normative beliefs. Thus, in many situations, people think that their emotional reactions will fall into line with their normative beliefs. In other situations, some people think that their emotional reactions have a life of their own. It is suggested that both normative beliefs and anticipated emotions affect decisions. PMID- 1403620 TI - The role of diagnosticity in stereotype formation: perceiving group means and variances. AB - Three experiments tested the hypotheses that while forming stereotypes of social groups, people abstract the central tendency and variability of different attribute dimensions to determine which ones best differentiate the groups and that more differentiating dimensions are more likely to become stereotypical in the sense of becoming strongly associated with the groups in memory. Supporting these hypotheses. Experiment 1 found that, after viewing behaviors performed by members of 2 groups, Ss characterized the groups more in terms of attribute dimensions indicating larger differences between the central tendencies of the groups, and Experiment 2 showed that this effect did not occur when Ss formed impressions of only 1 group. Experiment 3 found that Ss also characterized groups more in terms of attribute dimensions indicating lower within-group variability. PMID- 1403621 TI - Once a boring task always a boring task? Interest as a self-regulatory mechanism. AB - A process was proposed through which individuals regulate their motivation to perform necessary but uninteresting activities over time. If committed to continuing, individuals may engage in interest-enhancing strategies that can change the activity into something more positive to perform. In Study 1 Ss performed novel tasks and generated strategies to make regular performance interesting. In Study 2 Ss actually used these strategies primarily in conditions indicating a self-regulatory attempt: The task was currently boring, there was a perceived reason to continue (alleged health benefit), and a relevant strategy was available. Strategy use was associated with a change in activity definition and greater likelihood of subsequently performing the activity. In Study 3 Ss beliefs about how to maintain motivation to perform more everyday activities emphasized the importance of regulating interest relative to other self regulatory strategies. PMID- 1403622 TI - Gender and self-esteem. AB - Where does self-esteem (SE) come from? Three experiments explored the idea that men's and women's SE arise, in part, from different sources. It was hypothesized that SE is related to successfully measuring up to culturally mandated, gender appropriate norms--separation and independence for men and connection and interdependence for women. Results from Study 1 suggested that men's SE can be linked to a individuation process in which one's personal distinguishing achievements are emphasized. Results from Study 2 suggested that women's SE can be linked to a process in which connections and attachments to important others are emphasized. Study 3 demonstrated that failing to perform well on gender appropriate tasks engendered a defensive, compensatory reaction, but only in subjects with high SE. These findings are discussed with regard to their implications for the structure and dynamics of the self. PMID- 1403623 TI - Self-concept change and self-presentation: the looking glass self is also a magnifying glass. AB - Studies 1 and 2 showed that identical behaviors had greater impact on the self concept when performed publicly rather than privately. That is, the self-concept is more likely to change by internalizing public behavior than by internalizing behavior that is identical but lacks the interpersonal context. The self-concept change extends even to behavioral changes and occurs even when participants are unaware of being observed. In addition, those who are high in self-monitoring are more likely to internalize their behavior than those who are low in self monitoring. Study 3 provided evidence about what components of a public situation affect the internalization of behavior. Choice about making the self-portrayal, drawing on episodes from one's own past rather than relying on a yoked script, and expecting future interaction with the audience all increased the internalization of a public behavior. PMID- 1403624 TI - The aggression questionnaire. AB - A new questionnaire on aggression was constructed. Replicated factor analyses yielded 4 scales: Physical Aggression, Verbal Aggression, Anger, and Hostility. Correlational analysis revealed that anger is the bridge between both physical and verbal aggression and hostility. The scales showed internal consistency and stability over time. Men scored slightly higher on Verbal Aggression and Hostility and much higher on Physical Aggression. There was no sex difference for Anger. The various scales correlated differently with various personality traits. Scale scores correlated with peer nominations of the various kinds of aggression. These findings suggest the need to assess not only overall aggression but also its individual components. PMID- 1403625 TI - Optimism, coping, psychological distress, and high-risk sexual behavior among men at risk for acquired immunodeficiency syndrome (AIDS). AB - In a cohort of gay men responding to the threat of acquired immunodeficiency syndrome (AIDS), dispositional optimism was associated with less distress, less avoidant coping, positive attitudes as a coping strategy, and fewer AIDS-related concerns. Men who knew they were seropositive for human immunodeficiency virus (HIV) were significantly more optimistic about not developing AIDS than men who knew they were seronegative for HIV. This AIDS-specific optimism was related to higher perceived control over AIDS and to active coping among seropositive men only and to health behaviors in both serostatus groups. There was no relation of optimism to risk-related sexual behavior. It is concluded that optimism is psychologically adaptive without necessarily compromising health behavior. It is also concluded that it is useful to distinguish between event-based optimistic expectations and dispositional optimism. PMID- 1403626 TI - The motivational and emotional consequences of considering positive or negative possibilities for an upcoming event. AB - The hypothesis that attention to negative possibilities for an upcoming event can have advantages for performance in comparison with a more optimistic approach was examined in 2 studies. Focus of attention to positive or negative possibilities for a social interaction was manipulated for Ss previously identified as optimists or defensive pessimists in the social domain. In Study 1, negatively focused defensive pessimists performed better in their conversations than positively focused defensive pessimists on several dimensions (e.g., talk time, perceived effort, and sociability). Optimists' behavior was unaffected by the focus manipulation. However, all negatively focused Ss felt worse after their conversations than did positively focused subjects. Study 2 examined the cognitive process by which a negative focus may lead to positive behaviors. Some pessimists may benefit from an initial negative focus that is not accompanied by lowered expectations and that actually facilitates positive thoughts about the self. PMID- 1403627 TI - Gender characteristics and adjustment: a longitudinal study. AB - The present study used a prospective longitudinal design to investigate the long term developmental implications of gender-related interests and traits. Archival data were available for Ss in the R. R. Sears, Maccoby, and Levin (1957) study. Men, who at age 12 endorsed interests and undesirable traits more typically associated with women, had poorer social-personal adjustment at ages 31 and 41. No effects were found for women. Feminine expressive traits at age 31 did not impact on 41-year-old adjustment for either men or women, whereas masculine instrumental traits were positively related for both. These findings support a multidimensional view of gender and indicate that harsher consequences follow when adolescent boys endorse nontraditional gender-related interests and undesirable traits than when girls do so. PMID- 1403628 TI - The four faces of eve: a typological analysis of women's personality at midlife. AB - In an analysis of adult personality structure, types are defined as prototypes rather than as discrete categories. Using inverse factor analyses of archival Q sort descriptions, 4 type factors were replicated in a cross-validation design. These prototypes are interpreted as Individuated, Traditional, Conflicted, and Assured and are related to Rank's (1945) theoretical analysis of different modes of adjustment. These prototypes capture particular combinations of personality dimensions, such as Ego Resiliency, Ego Control, and the Big Five, and converge with the types identified by Block (1971). Further analyses using 13 clusters of scales from 3 broad-band self-report inventories validated the Q-sort-based interpretations and showed a distinct and theoretically consistent patterning for each of the types. PMID- 1403629 TI - Leaving the lesbian lifestyle. PMID- 1403630 TI - Can homosexuals really change? PMID- 1403631 TI - Is marriage worth the work? PMID- 1403632 TI - Faith in recovery. Spiritual support after an acute MI. AB - Data from a sample of ninety AMI patients indicate that the majority of these patients find that their spiritual views are a source of help, both at hospital discharge and during early recovery at home. Conversely, a small group of these patients said they did not receive help. Since the remainder of the patients were unsure if they received help from their religious or life views, I believe that all AMI patients could benefit from spiritual care provided by Christian nurses. Findings also indicate that subjects who experienced spiritual support at home also experienced decreased stress. PMID- 1403633 TI - For Pete's sake. PMID- 1403635 TI - Rethinking the Golden Rule. PMID- 1403634 TI - Sexual harassment--what should I do? PMID- 1403636 TI - Detection of incident HIV infection by PCR compared to serology. AB - In order to determine the most sensitive method for the early detection of HIV infection, polymerase chain reaction (PCR) and serology were compared using matched peripheral blood mononuclear cells (PBMC) and serum samples taken sequentially at 3-month intervals on 17 HIV seroconverters. All samples from the time of enrollment in the study to the time of seroconversion were studied. [There were only two of the 17 cases where PCR and antigen positivity preceded EIA detectable seroconversion.] Initially, one of these cases was found to be PCR positive 11 months prior to seroconversion, however DNA fingerprinting techniques indicated that the early positive specimen did not belong to the subject in question. In a single subject, PCR was negative at the time of serologic evidence of infection but was positive at the next sampling 3 months later. In the remaining 14 cases, PCR was positive at the same sample time as full or partial seroconversion as determined by three EIA screening tests and Western blot. EIA antibody screen tests showed variability in detection of early HIV antibodies. We found no evidence for prolonged HIV infection prior to seroconversion. PCR offers little if any advantage over serology in the early detection of HIV infection in adults. PMID- 1403637 TI - Acidification modified p24 antigen capture assay in HIV seropositives. AB - The p24 antigen is only detectable in a minority of asymptomatic HIV infected individuals, which is in part felt to be secondary to immune complex formation with p24 antibody. We sought to determine if the recovery of p24 antigen could be enhanced by an acidification procedure in an attempt to dissociate p24 antibody antigen complexes. We tested 291 HIV antibody positive serum samples in duplicate, comparing the standard Coulter p24 Antigen Assay with the same assay which was modified by pretreating samples for 60 min with 1.5 M glycine (pH 1.85) and then neutralizing the sample with 1.5 M Tris (pH 9.0). Using the assay cutoff (approximately 7.8 pg/ml), the standard assayed sera and the acid pretreated sera were positive in 65/291 (22.3%) and 167/291 (57.4%) of the samples, respectively. This difference between procedures was statistically significant (p < 0.0001) by McNemar chi 2. There was also a statistically significant difference between Walter Reed stages for p24 antigen quantification by ANOVA (p < 0.0001). We have demonstrated that the detection of p24 antigen may be significantly enhanced by acid pretreatment of sera which dissociates immune complexed antigen. We have also shown significant differences exist between Walter Reed stages for quantitative p24 antigen levels. Enhanced detection of p24 antigen may be important prognostically and may allow for the monitoring of antiretroviral therapy. PMID- 1403638 TI - Cytokine dysregulation in AIDS: in vivo overexpression of mRNA of tumor necrosis factor-alpha and its correlation with that of the inflammatory cytokine GRO. AB - The human immunodeficiency virus establishes an intimate interaction with the immune system. The virus can use cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (Il-1), to regulate its own expression by modifying the normal immunoregulatory network. We demonstrate that mRNA of the cytokine TNF alpha from peripheral blood mononuclear cells is overexpressed in virtually all patients with AIDS who do not have active opportunistic infections compared with uninfected volunteers (p < 0.0001). This overexpression correlates with elevated mRNA levels of the recently discovered GRO (p < 0.05), a cytokine involved in the inflammatory response. PMID- 1403639 TI - AIDS incidence and income. AB - Since 1987, the annual increases of AIDS incidence among homosexual and bisexual men have slowed but the increases among other risk groups have continued unabated. Although indirect evidence suggests the incidence change is related to medical care for HIV disease delaying the onset of AIDS, other explanations are also possible. To examine the incidence change from a different perspective, we classified the residents of Philadelphia (PA, U.S.A.) with AIDS by the per capita income of their census tracts of residence. AIDS incidence increased steadily in the lowest income tercile, showed continuing but smaller increases after 1987 in the middle tercile, and was level after 1987 in the highest income tercile. The relationship between income and changes of incidence persisted after stratification on race or mode of infection with HIV. Income was associated with private medical insurance at the time of diagnosis of AIDS (59% privately insured in the highest income tercile, 24% in the lowest) and with median survival after a diagnosis of AIDS (467 days in the highest tercile of income, 359 days in the lowest). These observations are consistent with a medical treatment benefit that reaches the highest tercile of income and does not reach the lowest one. PMID- 1403640 TI - AIDS prevalence by income group in Philadelphia. AB - We sought to track recent changes in AIDS incidence and prevalence in the city of Philadelphia (PA, U.S.A.) using morbidity and mortality data reported to the health department. We stratified the data by the mean per capita income in census tracts where people with AIDS resided. Estimates made without adjustment for the time lag between events and their entry into the database undercount both recent AIDS diagnoses and recent AIDS deaths. Therefore, we used a previously published method to adjust for the lag in reporting diagnoses and developed a method to adjust for the lag in reporting deaths. We calculated prevalent cases as the difference between cumulative cases and cumulative deaths. Between 1988 and 1990, annual AIDS incidence per 100,000 Philadelphia residents increased by 21% (from 25.9 to 31.4) and AIDS prevalence per 100,000 population increased by 62% (from 30.2 to 48.8). AIDS prevalence increased 113% (from 29.8 to 63.6) in low-income tracts, 88% (from 27.8 to 52.3) in middle-income tracts, and 14% (from 32.5 to 37.2) in high-income tracts. The 62% increase in AIDS prevalence and the shift toward people in poorer neighborhoods imply a need for public funding for AIDS care that is far larger than would be suggested by the general 21% increase in AIDS incidence over the same period. PMID- 1403641 TI - A model-based estimate of HIV infectivity via needle sharing. AB - Critical to understanding the spread of the human immunodeficiency virus via needle sharing among drug users is the infectivity, i.e., the conditional probability of infection given injection with a shared, contaminated syringe. A simple mathematical model was constructed that relates infectivity to the prevalence of infection in needles used by drug users, the mean shared injection frequency among drug users, the probability that a needle is disinfected prior to use, and the mean AIDS incubation time. Three of these parameters have been estimated using data from the New Haven, Connecticut legal needle exchange program. Using the polymerase chain reaction to test for the presence of HIV proviral DNA in a sample of returned needles, we determined that 67.5% were HIV positive. We were able to estimate shared injection rates and disinfection rates from surveys of drug users enrolled in the needle exchange and our syringe tracking system. Current estimates of the mean AIDS incubation time are available in the literature. Our model implies that the probability of infection per injection with a contaminated syringe equals 0.0067, which is slightly higher than the transmission probabilities of 1/300 to 1/200 estimated from needlestick studies, and a factor of 3 higher than estimates of the probability of HIV transmission per vaginal sex act from a infected man to an uninfected woman. PMID- 1403642 TI - HIV testing and sexual behavior among intravenous drug users in Bangkok, Thailand. AB - The relationships between previous HIV counseling and testing and sexual behavior were examined among injecting drug users in Bangkok. Six hundred one i.v. drug users (IVDUs) were recruited from drug treatment programs in November of 1989. A standardized interview on AIDS risk behavior was administered and a blood sample was collected for HIV testing of the 601 people. Fifty-six percent reported that they had not been previously tested (NPT), 15% had previously tested positive (PT+), and 29% had previously tested negative (PT-). Previous testing was associated with higher levels of safer sex and contraception with primary partners: 56% of the PT+ people with regular partners reported using condoms at least some of the time with that partner, compared with 28% of the PT- and only 20% of the NPT people. Similarly, 89% of the PT+ and 72% of the PT- people, compared with 59% of the NPT people, reported practicing some form of contraception with regular partners. The results strongly support the utility of HIV counseling and testing as a method of reducing heterosexual and perinatal HIV transmission among IVDUs in Bangkok. PMID- 1403643 TI - Influence of HIV-1 infection and cigarette smoking on leukocyte profiles in homosexual men. The Multicenter AIDS Cohort Study. AB - The interaction between the effects of HIV-1 infection and cigarette smoking on leukocyte profiles was studied in 307 HIV-1 seroconverters in the Multicenter AIDS Cohort Study (MACS). Longitudinal data for white blood cell (WBC) counts, WBC differentials, T cell subsets, and smoking behavior were collected semiannually for up to 7 years. Prior to seroconversion, total WBC count increased in direct proportion to daily cigarette consumption, but this effect disappeared within 3 years of seroconversion. Analyses of WBC subsets (lymphocytes, monocytes, and granulocytes) and lymphocyte subsets (CD4+, CD8+ and non-T[CD3-]) showed that smoking had only minor effects on the proportions of these cells. In contrast, HIV-1 seroconversion was associated with a dramatic decrease in CD4+ lymphocyte percentage, a large increase in CD8+ lymphocyte percentage, a small increase in total lymphocyte percentage, and small decreases in the non-T lymphocyte and granulocyte percentages. These findings indicate that the effect of smoking on CD4 cell counts is (a) nonspecific, (b) maximal in seronegative individuals; and (c) lost by 3 years after seroconversion. Although the mechanism of the loss of smoking-induced leukocytosis after seroconversion remains to be determined, our results suggest that the effects of smoking are not likely to be important in the clinical use of leukocyte measurements, including measurements of CD4 lymphocytes, in individuals who have been HIV-1 seropositive for more than 3 years. PMID- 1403644 TI - National study of knowledge of AIDS, testing patterns, and self-assessed risk among health care workers. AB - We conducted a study to assess the level of AIDS knowledge, testing behavior patterns, and self-assessed risk of contracting AIDS for a representative sample of health care workers in the United States. The study was based on data collected in the 1989 AIDS Knowledge and Attitudes Supplement to the National Health Interview Survey. Health care workers in four occupational groups were compared with other members of the labor force and with one another. The survey included 1,620 respondents identified as health care workers and 25,217 respondents with occupations other than in health care. Health care workers were more knowledgeable about AIDS than were other workers; approximately 55% and 25%, respectively, reported knowing a lot about AIDS. They were also more likely to have been tested (34%) than other workers (24%) and to have done so voluntarily (28% versus 14%). Health care workers also believed they had higher risk of contracting AIDS (8% versus 3%), although they were about equally likely to report being in one of the six high-risk groups. Among health care workers, those in the health diagnosing occupations were the most knowledgeable about AIDS (74% reported knowing a lot) and were the most likely to have been tested (41% were tested at least once). Health service workers were the least knowledgeable; only 38% reported knowing a lot about AIDS and only 26% reported being tested. PMID- 1403645 TI - Racial misclassification of American Indians with AIDS in Los Angeles County. AB - American Indian/Alaska Natives (AI/ANs) appear to be underrepresented in AIDS surveillance statistics. We estimated the accuracy of racial classification and reporting completeness of AIDS among AI/ANs in Los Angeles County by surveying community-based organizations (CBOs) that provide services to persons with AIDS and then comparing the survey to AIDS surveillance data. The surveyed CBOs reviewed 6,500 records and found 60 Native American (the classification used by CBOs for AI/ANs) clients with AIDS compared with six AI/AN AIDS cases reported to the Los Angeles County AIDS surveillance registry. Racial classification was evaluated for 37 (62%) of the 60 Native American CBO clients. Only 11 (30%) of the 37 were verified as AI/ANs. The remaining 26 (70%) misunderstood the racial nomenclature and were reclassified by the CBOs as other races. Of 10 verified AI/AN clients for whom names were available, eight (80%) had been reported to the AIDS registry. However, seven (88%) of these eight were erroneously reported as other races. Racial misclassification accounts for much of the underrepresentation of AI/ANs in the Los Angeles County AIDS surveillance registry. PMID- 1403646 TI - The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC. AB - The HIV Tat protein is able to upregulate the transcription by RNA polymerase III of cotransfected or endogenous cellular Alu-repeated sequences in both HeLa and Jurkat T cells. This effect is mediated by an increase in the activity of transcription factor TFIIIC, which binds to the B box in the RNA polymerase III Alu promoter. This is the first example of an effect of the Tat protein on the transcription of a cellular gene or on the activity of a cellular transcription factor. The significance of this effect for the life cycle of HIV and its interaction with infected cells is discussed. PMID- 1403647 TI - Clonal dominance: cause for a limited and failing immune response to HIV-1 infection and vaccination. AB - Oligoclonal and monoclonal antibody populations against different HIV-encoded proteins are common in sera from healthy HIV-1-infected individuals. This is especially important when it includes functional antibody repertoires directed at neutralizing cell free virus or inhibiting cell fusion of virus-infected cells. In the host, during the acute viral syndrome following HIV-1 infection, a rapidly replicating, cell-free and genotypically homogeneous viral population is known to arise from the transmitted viral inoculum. Dominant B and possibly T cell clones responsible for both functional and nonfunctional antibodies appear to arise early in response to this initially homogeneous cell-free viral population heralding seroconversion. During the viremic phase, deposition of cell-free virus as either complement coated or as immune complexes (iccosomes) within the germinal centers results in continued and long-term boosting of primed B cells. This saturation of antigen presenting germinal centers and the presence of limited, immunodominant cross-reactive epitopes on the envelope glycoprotein of the closely-related and immune selected viral quasispecies in the host appear to continue the boosting effect of the primed secondary response. This repertoire freeze appears to be responsible for limiting the recruitment of new uncommitted B cells to other functional epitopes or affinity maturation of B-cell clones to escape variants and the subsequent production and quality of functional antibody against the evolving/selected virus populations. This may include in addition to neutralizing and cell fusion inhibiting antibody, direct complement-fixing and/or NK-directed antibody-dependent cell-mediated antibody as well as various effector, helper, or T cell-mediated activity. In addition to antiviral antibody responses, antibody directed to other invading pathogens or opportunistic organisms may also be clonaly restricted. Antibody facilitating infectivity or blocking effective immunity may also be included in this phenomena and thus be over represented by such a mechanism. AIDS vaccines utilizing the envelope must identify these epitopes to avoid creating clonal dominance and therefore possibly limit the breadth and specificity of a humoral response following infection. Furthermore, immunotherapeutic approaches designed to recruit humoral immune effector function must be able to overcome the dominance of noneffective antibodies and restore a normal polyclonal immune response against HIV. Further research, therefore, into the humoral and cellular dysregulating properties of the HIV-1 envelope is warranted. PMID- 1403648 TI - Report of a consensus workshop, Siena, Italy, January 17-18, 1992. Early diagnosis of HIV infection in infants. AB - To promote progress in the research and development of early diagnostic tests for HIV in young children an international workshop was held on January 17-18, 1992, in Siena, Italy. Experts on pediatric AIDS, diagnostic retrovirology, and immunodiagnosis discussed and summarized the state-of-the-art and made recommendations for general application of several tests and further evaluation and continued research for other candidate tests. From the discussions it was clear that the field has advanced beyond the time when it was necessary to wait until the infant reached 18 months of age before attempting the diagnosis with conventional serologic tests for HIV. About half of infected infants can now be identified at birth, approximately 90% by 3 months of age, and almost all by 6 months of age using HIV culture and polymerase chain reaction assays. IgA antibody tests and p24 antigen tests have also proved useful, although they are not as sensitive in newborn infants. The fact that HIV can be detected in only one-half of infected infants at the time of birth points to the need for further research on the timing of transmission and the natural history of perinatally acquired HIV infection to understand the limitations of current early diagnostic tests and to develop new approaches to overcome these problems. PMID- 1403649 TI - Uses and implications of the contextual approach to child custody decisions. AB - Child custody litigation signals parental conflicts that have serious implications for a child's long-term development. The authors describe a family systems approach to child custody decision making--the contextual approach, derived from contextual family theory. A case study analysis and pilot study illustrate the use of the approach with a small group of families who turn to the legal system to resolve custody or visitation disputes. The findings suggest the approach's usefulness in helping families create alternatives to continued disputation. The findings also reinforce the need for further research to test the preventive potential of the approach in reducing returns to court. PMID- 1403650 TI - In support of sibling inclusion: a literature review. AB - The responses of siblings to a childhood mental illness have been conceptualized in different ways. When siblings have not been ignored, they have been viewed most frequently as an influence upon the illness or as subject to the same dynamics that were believed to have caused the mental illness. As conceptualizations of the causes of mental illness have changed, the literature on siblings has changed to focus on the impact of the illness on the sibling. How siblings and sibling relationships are conceptualized has important implications for clinical research and practice. More research is needed to understand the sibling experience in childhood mental illness. Clinicians can do more for the family if all of the family dynamics and responses to the illness are explored. PMID- 1403651 TI - A forest of matches. PMID- 1403652 TI - Difficulties with teens: can nursing consultation help? AB - Child/youth problems and psychiatric hospitalizations are increasing. A literature review suggests that there is an increased need for more nurses with the knowledge and skills necessary to work in this specialty area. The review also suggests that providing psychiatric nursing consultation services is one way to help direct care staff to strengthen or develop these skills. The authors describe a consultation project that took place on a newly developed 15-bed adolescent program in a 30-bed private psychiatric hospital. They examine the effectiveness of consultation sessions, ascertained through both verbal and written evaluations of staff members. The outcome suggests that psychiatric nursing consultation services can be an important contribution in expanding the knowledge base of direct care staff (child care specialists and nurses) who work with the hospitalized adolescent psychiatric patient. PMID- 1403653 TI - Practicing in partnership with families in the inpatient setting. PMID- 1403654 TI - The Attending Nurse: a new role for the advanced clinician. AB - The Attending Nurse Model as a unique role for the advanced practitioner was implemented and evaluated in an acute care psychiatric setting with an adolescent patient population. Program evaluation results demonstrated that the Attending Nurse role increased general satisfaction and role clarity while decreasing role tension. In addition, the role increased communication with patients' family members. Comparisons are made between the traditional primary nurse and the Attending Nurse roles. PMID- 1403655 TI - [Recent advances in the carbon-carbon bond forming reactions with alpha chlorosulfides]. AB - This review describes our recent studies on the carbon-carbon bond forming reactions of alpha-chlorosulfides with arenes, alkenes, and alkynes. Applications of these reactions to the synthesis of natural products are also presented. PMID- 1403656 TI - [Asymmetric synthesis of nitrogen-containing biologically active compounds utilizing intramolecular aminocyclization to olefin of secondary allylic alcohols]. AB - The progress of the asymmetric syntheses of nitrogen-containing biologically active compounds such as pyrrolidine, pyrrolizidine, indolizidine alkaloids, and unusual amino acids has been reviewed. Our recent advances in taking advantage of stereoselective aminocyclization of homochiral N-alkenyl urethanes and thioimitates containing allylic hydroxyl group have provided an attractive entry into the functionalized pyrrolidine skeletons as chiral building blocks. A promising approach to a number of biologically active compounds such as alkaloids has emerged. PMID- 1403657 TI - [Protective effects of the bark of Myrica rubra Sieb. et Zucc. on experimental liver injuries]. AB - The methanol extract from the bark of Myrica rubra SIEB. et ZUCC. showed protective effects on liver injuries induced by carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) in rats. In this study, the fractions and some compounds from the bark of M. rubra were investigated for the protection against CCl4 inducing liver injuries in rats. The active principles for the protection were recognized in two fractions (M-3 and M-5 Fr. 1) obtained from the methanol extract, and one of the active principles in the fraction (M-3) was found to be myricanol 5-O-beta-D-(6'-O-galloyl)-glucopyranoside. In addition, these fractions protecting liver injuries induced by CCl4 showed significant protective effects against cholestasis induced by ANIT. PMID- 1403658 TI - [Subcellular distribution of porphyrins and anti-lipid peroxidative effect in protoporphyrin-administered rat liver]. AB - The distribution and the anti-lipid peroxidative effects of porphyrins in the hepatic subcellular fractions in rats were studied after intravenous administration of protoporphyrin (PP). PP and/or PP-derived porphyrins were mainly distributed in the membrane-containing fractions of 600 x g-, 10,000 x g- and 100,000 x g-sediment from the liver homogenates of rats receiving a 20 mg/kg dose of PP. The lipid peroxidation induced by L-ascorbic acid in the fractions of 600 x g-, 10,000 x g- and 100,000 x g-sediment from the PP-treated rats was suppressed during 1-168 h, 1-168 h and 12-168 h, respectively, after the PP treatment. The suppression of the peroxidation in the liver mitochondria from the PP-treated rats was further enhanced by the addition of the hepatic cytosol from the PP-treated rats. The extent of the suppression by the addition of the cytosol from the PP-treated rats at 24 h after the PP administration was greater than those at 0 and 168 h after the PP administration. These results indicate that PP and/or PP-derived porphyrins distributed in the liver still exert antioxidative actions and that there might exist some unknown factors enhancing the actions in the hepatic cytosol. PMID- 1403659 TI - [Effect of shikonin and its derivatives, pentaacetylated shikonin (MDS-004) on granuloma formation and delayed-type allergy in experimental animals]. AB - Of twelve reduced and acetylated derivatives of shikonin, a chemical constituent of Shikon, the accelerating activity on granuloma formation and the inhibitory activity on delayed-type allergy were investigated in order to find a compound having more characteristic effect than shikonin on wound healing in experimental animals. As a result, it was found that a reduced and pentaacetylated derivative of shikonin, MDS-004, has more excellent pharmacological activity. MDS-004 (0.1-1 mg/pellet) accelerated dose-dependently felt-pellet-induced granuloma formation when given topically together with felt-pellets in rats. It also produced strong inhibition against delayed-type allergies (ear edema) caused by oxazolone and dinitrofluorobenzene by topical application of up to 1 mg/ear to the ear skin of mice; its potency was far superior to that of shikonin. Orally administered MDS 004, unlike shikonin, inhibited carrageenan-induced hind paw edema, and exhibited tendency to heal acetic acid-induced gastric ulcer in rats. However, MDS-004, as well as commercial wound healing drugs tested and shikonin, did not show any healing action in the incised and open wound models in rats, if applied topically to the wound as 5 and 10% powders. On the other hand, MDS-004 did not produce irritative action on the ear skin at a topical dose of 1 mg/ear different from shikonin, and any behavioral changes after oral administration of 100 mg/kg in mice. These results suggest that a white powder MDS-004, different from deep purple shikonin, has accelerating action on granuloma formation without irritative action and stronger inhibitory action on delayed-type allergy by topical application than shikonin. PMID- 1403660 TI - [Determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma by ion-pair high-performance liquid chromatography]. AB - A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma. This method was compared with other two methods, i.e. ion-suppression and phosphate buffer methods. Sennoside A was eluted without interference in this ion-pair method, while the determination of sennoside A was interfered by co-existing components in the other two methods. PMID- 1403661 TI - [Pharmacological studies on leaf of Arctostaphylos uva-ursi (L.) Spreng. IV. Effect of 50% methanolic extract from Arctostaphylos uva-ursi (L.) Spreng. (bearberry leaf) on melanin synthesis]. AB - Effects of 50% methanolic extract (U-ext) from the leaf of Arctostaphylos uva ursi (L.) Spreng. (bearberry leaf) on melanin synthesis were investigated in vitro. The U-ext and arbutin isolated from the bearberry leaf had an inhibitory effect on tyrosinase activity. Furthermore, the U-ext inhibited the production of melanin from dopa by tyrosinase and from dopachrome by autoxidation. These results suggest that the bearberry leaf was found to be an effective inhibitor of the production of melanin. PMID- 1403662 TI - [Molecular interaction in pharmaceutical solution, solubilization, partition, and stability of drugs]. AB - The pharmaceutical studies carried out by the author during 40 years were reviewed from the viewpoint of molecular interaction. Included subjects are: electrostatic interaction between drug ions, ion pair formation and its partition to organic phase, drug solubilization by adjuvants, partition of drugs between aqueous and micellar phases, cyclodextrin inclusions, human serum albumin binding and drug stability related to the esterase-like activity of the albumin, and oral liposome preparation of vitamin K1. The drug stabilities related to those molecular interactions were emphasized. PMID- 1403663 TI - [Development of multicomponent immunoassay and micro-localization analysis by laser-photoacoustic and microscopic image analyzer]. AB - Laser photoacoustic spectroscopy (PAS) has a potential to be developed as a sensitive and solid-phase analytical method and was applied to enzyme immunoassay. The test sample for immunoassay was prepared by adsorbing multi component immunoglobulins on a nitrocellulose membrane filter. Human lambda- and kappa-chains, which are used as a principal indication of malignant lymphoreticular disease, and immunoglobulin G were used as model proteins, and PAS immunoassay was applied to the individual detection of these three proteins in the urine. Furthermore, in order to develop a sensitive analysis for particular biological components in tissues or cells, laser photoacoustic microscopy (PAM) and video intensified microscopy (VIM) were developed. PAM was shown to be applicable to the detection and quantification of human lambda-chain in a micro-region of the tissue sections of the human fetal spleen and pancreas. VIM was applied to the detection of stimulation-response processes in a cell. By using neutrophils which are stimulated by many substances and produce active oxidants as the results, dynamic changes in the stimulation-response process in a living cell were visualized as fluorescence or chemiluminescence images by the VIM system. PMID- 1403664 TI - [Determination of synephrine in oriental pharmaceutical decoctions containing Aurantii nobilis pericarpium by ion-pair high-performance liquid chromatography]. AB - A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of synephrine in oriental pharmaceutical decoctions containing Aurantii Nobilis Pericarpium. An ODS column and a mixture of water, acetonitrile, sodium dodecyl sulfate and phosphoric acid (65:35:0.5:0.1) as a mobile phase were used for the separation. Synephrine was eluted without interference by other co-existing components within 15 min. PMID- 1403665 TI - [Oxidation of hydrogen sulfide with cell-free extract of Hyphomicrobium neptunium ATCC 15444]. AB - Soluble (Fr. 1) and membrane (Fr. 2) fractions were prepared from the cell-free extract of Hyphomicrobium neptunium ATCC 15444, and their effects on the oxidization of hydrogen sulfide (H2S) were studied. When H2S gas was supplied to Fr. 1 and Fr. 2, sulfur in both fractions and the majority of thiosulfate ion in Fr. 1 were detected. The sulfide-oxidizing activity in Fr. 2 but not in Fr. 1 was inhibited by the addition of diethyldithiocarbamate, suggesting that Fr. 1 and Fr. 2 have different types of sulfide-oxidase, and that Fr. 2 would include cytochrome c dependent sulfide oxidase. It was also found that thiosulfate ion was formed from sulfur and sulfite ion by adding Fr. 1. However, the pronase treatment of Fr. 1 did not influence on the formation of thiosulfate ion. These results suggest that H2S was oxidized to sulfur and sulfite ion by two types of sulfide oxidase and sulfur oxidase in H. neptunium ATCC 15444, and that the sulfite ion changed rapidly to thiosulfate through a non-enzymatic reaction with sulfur. PMID- 1403666 TI - [The mechanism of the renal excretion of disopyramide in rats. I]. AB - The mechanism involved in the renal excretion of disopyramide (DPM) is still incompletely understood. The purpose of this study was to examine the renal handling of DPM and the interactions between DPM and several organic anionic or cationic drugs related to the renal tubular secretion, using the renal clearance and renal cortical slices uptake techniques in rats. The clearance ratio of DPM was greater than that of glomerular filtration and this suggests the tubular secretion of DPM. The clearance ratio of DPM did not change after infusion of either anionic drugs (p-aminohippurate and probenecid) or a cationic drug (cimetidine). The results of time and concentration-dependent experiments using renal cortical slices demonstrated that DPM was accumulated against a concentration gradient by a saturable process. Inhibition of uptake by 2,4 dinitrophenol and cyanide indicated an energy dependence. DPM uptake was considerably inhibited by the cationic drugs, cimetidine and quinine, suggesting that DPM was transported by the cation transport mechanism. Probenecid, a competitor for the anion transport mechanism, moderately inhibited DPM uptake. PMID- 1403667 TI - [Limonoids in Phellodendron amurense (Kihada)]. AB - Limonoids and their glucosides in the seeds and barks of Phellondendron amurense (Kihada) were analyzed. The seeds contained limonin (1950 ppm), obakunone (20 ppm), limonin 17-beta-D-glucopyranoside (820 ppm) and obakunone 17-beta-D glucopyranoside (1360 ppm). The barks contained limonin (6760 ppm), obakunone (1240 ppm) and nomilin (270 ppm). PMID- 1403668 TI - Binary combination effects of some pharmacologically active chemicals as promoters of tumorigenesis. AB - Identification of potential interactions in exposures either to simultaneous or sequential combinations of carcinogenic chemicals and chemicals that modify carcinogenesis poses considerable difficulties in human health risk assessments. Studies of experimental carcinogenesis over the past four decades have revealed that many pharmacologically active agents possess tumorigenesis-promoting properties. The effort to identify the possible chemical structural basis of interactions of binary combinations of carcinogenic chemicals and chemical agents that modify carcinogenesis led to the identification of a class of structurally diverse and pharmacologically active tumorigenesis promoters that are known as pharmaceuticals. The chemical class-class interactions of carcinogens and pharmaceutical agents with reported tumorigenesis-promoting properties and the possible biochemical mechanism(s) that underlie such interactions are discussed. PMID- 1403669 TI - Physiological modeling of disposition of potential tumor-imaging radiopharmaceuticals in tumor-bearing mice. AB - Radiopharmaceuticals have great potential in the early detection of human tumors. Three potential 99mTc-labeled platinum compounds based on cisplatin have been synthesized and tested in tumored mice. This report presents the analysis of the disposition data obtained after a single intravenous injection with an empirical, physiologically based pharmacokinetic model. The radioactivity of each radiopharmaceutical after administration was measured in blood, urine, and 15 tissues, including tumor. Parameters included in the model were tissue volumes (experimentally determined), tissue blood flows (determined from literature values), tissue:blood extraction ratios (determined by nonlinear least-squares regression with MULTI-FORTE), and clearance terms (also determined by nonlinear least-squares regression). Data were weighted by the reciprocal of the square of the observed values. Good fits to the experimental data were obtained. As expected, the compound producing the best tumor:blood profile (3) also had the highest tumor extraction ratio (6.2 versus 2.0 and 1.3 for 1 and 2, respectively). Total body clearance values for the radioactivity associated with the three compounds 1-3 were calculated to be 0.09, 0.04, and 0.016 mL/min, respectively. Analysis of data with such an empirical, physiologically based model may assist future development of suitable tumor-imaging agents. PMID- 1403670 TI - Release of polyionizable compounds from submicrometer oil-in-water emulsions. AB - A novel, general, theoretical equation that describes the release of polyionizable compounds from submicrometer emulsions was derived and evaluated. The model accounts for simultaneous partitioning, interfacial activity, and adsorption to surfactant for n independent drug species and j surfactant species in a single emulsion system. Under the appropriate conditions, this model collapses to a previously described model for submicrometer emulsions. The model was tested for submicrometer emulsions containing a model dibasic compound (quinine sulfate). Drug release behavior was observed at pH 3.00, 5.07, and 7.50 in the presence and absence of an anionic surfactant (sodium lauryl sulfate). At each pH, the proposed theory describes the observed release behavior. At all pHs studied, a substantial amount of quinine was adsorbed to the surface of the oil droplet. Presumably, this behavior was largely the result of electrostatic attraction between ionized drug and sodium lauryl sulfate at the oil-water interface. Adsorption constants were evaluated for complexation of cationic and dicationic species of quinine to sodium lauryl sulfate, and the adsorption constant of the cationic species was larger, presumably because of the ionic nature of the surfactant. PMID- 1403671 TI - Chloride-37 nuclear magnetic resonance spectroscopic study of binding of salicylic acid and other hydroxybenzoic acids to the band 3 anion transport protein of human erythrocytes. AB - Chloride-37 nuclear magnetic resonance spectroscopy was used to investigate the displacement of chloride (Cl-) from binding sites on band 3 anion transport protein in human erythrocytes by salicylic acid and five other hydroxybenzoic acids (HAs). All the HAs studied displaced Cl- from these binding sites. The association constants for binding of the HAs to band 3 anion transport protein were larger than that for Cl- and dependent on the specific structural features of the molecule, rather than general physicochemical characteristics. PMID- 1403672 TI - A kinetic study of the role of band 3 anion transport protein in the transport of salicylic acid and other hydroxybenzoic acids across the human erythrocyte membrane. AB - The mechanism of transport of salicylic acid and five other hydroxybenzoic acids across the human erythrocyte membrane was investigated. The specific anion transport inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, reduced but did not totally abolish transport of these acids. This observation suggests that these acids are transported by two parallel processes, one involving the band 3 anion transport protein channel and the other probably involving passive diffusion of the un-ionized molecule. The activation energies for membrane transport were large (99-127 kJ.mol-1), an observation that is consistent with the rate-limiting step for anion transport being the conformational change of the band 3 anion transport protein. PMID- 1403673 TI - Transport of drugs through human erythrocyte membranes: pH dependence of drug transport through labeled human erythrocytes in the presence of band 3 protein inhibitor. AB - To reveal the role of the band 3 anion transport protein of the erythrocyte membrane in drug transport through the membrane, the possible effects of inhibitors of anion transport on the permeability of some anionic drugs were examined. The amounts of these drugs that permeated varied markedly with the pH of the outer medium around human erythrocytes that contained the band 3 protein inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS). In the pH range 7.0-8.0, the membrane permeability of drugs through DIDS-treated erythrocytes was affected by a slight pH change (0.2), whereas that through the intact erythrocytes was not pH dependent. These results suggest that the band 3 protein acts not only as a channel for the transport of anions or some anionic drugs but also as protection for the transport system from changes in the pH of the outer medium. PMID- 1403674 TI - Pharmacokinetics of parenteral 13-cis-retinoic acid formulations in rats. AB - The pharmacokinetics of three 13-cis-retinoic acid formulations were studied after intraperitoneal (ip) administration to rats. Rats were given ip injections of 2.5 mg of 13-cis-retinoic acid per 360 g of body weight; the drug was administered as an alkaline solution, suspended in corn oil, or as a mixture with polysorbate 80. The alkaline solution was also given intravenously (iv) via the tail vein as a control. The mean elimination rate constant, calculated from data from iv administration, was 0.72 +/- 0.088 h-1 (r = 0.988). The peak concentration in plasma and the time to reach this maximum were 14 mg/L and 0.5 h, 22 mg/L and 2 h, and 10 mg/L and 1 h for the drug administered as an alkaline solution, suspended in corn oil, and as a mixture with polysorbate 80, respectively. The areas under the concentration-time curve (concentration in plasma versus time) were 34.9 +/- 8.78 mg.h/L for the iv dose and 34.1 +/- 9.97, 62.4 +/- 32.3, and 25.9 +/- 12.0 mg.h/L for the ip doses of alkaline solution, suspension in oil, and mixture with polysorbate 80, respectively. Because of the rapid increase of concentration in plasma, which is identical to that of the iv profile, and the ease of its handling and preparation, the ip administered alkaline solution is the preferable formulation. PMID- 1403675 TI - Anticonvulsant properties of some Mannich bases of conjugated arylidene ketones. AB - Thirty 1-aryl-5-dimethylamino-1-penten-3-one hydrohalides and related compounds were prepared as candidate anticonvulsants and evaluated in maximal electroshock seizure (MES), subcutaneous pentylenetetrazole threshold, and neurotoxicity screens. Following administration by the intraperitoneal route, many of the compounds were active in the MES screen, whereas only 10% of the Mannich bases afforded protection in the subcutaneous pentylenetetrazole test. Quantitation of half of the compounds prepared revealed that many had activity comparable with that of clinically useful drugs in the MES screen. The anticonvulsant properties of eight of the compounds following oral administration were reduced considerably or abolished compared with those following intraperitoneal administration. Various synthetic strategies for future development of potential anticonvulsants are outlined. PMID- 1403676 TI - Effects of cytochalasin, colchicine, and ethylenediaminetetraacetic acid on linoleic acid transport across rat jejunal enterocytes. AB - The involvement and the site of interference of the cytoskeleton in the transport of linoleic acid across the rat jejunum was investigated by administration of microfilamentous and microtubular altering agents such as cytochalasin, colchicine, and ethylenediaminetetraacetic acid (EDTA). An isolated jejunal segment was perfused with a buffer containing labeled linoleic acid, and portal blood and perfusate samples were collected concomitantly at 5-min intervals and assayed for their radioactivity. At the end of the perfusion, the amount of radioactivity retained in the intestine was also determined. The results were analyzed by using a three-compartment physical model that allows the determination of mucosal and serosal permeability coefficients, from which changes in the permeability of the mucosal and serosal membranes were assessed. Cytochalasin decreased the permeability of the mucosal membrane to linoleic acid, but not that of the serosal membrane. The administration of colchicine, EDTA, or cytochalasin + colchicine increased the permeability of the serosal membrane but did not affect the mucosal membrane. PMID- 1403677 TI - Pharmacokinetics and pharmacodynamics in the design of controlled-release beads with acetaminophen as model drug. AB - Relationships between pharmacodynamics (drug concentration and effect) and pharmacokinetics were used to develop an oral, controlled-release-bead dosage form. Reported pharmacodynamic data were used with pharmacokinetic curves to identify effective therapeutic drug concentrations for optimum therapy for a drug with a "deep tissue" effective compartment. The commonly used, over-the-counter, non-narcotic, analgesic-antipyretic acetaminophen (APAP) was used as the model drug. Data reported in the literature were used to compare analgesic and antipyretic efficacy. Computer simulations were performed with MAXSIM (version 3.01) to suggest a zero-order drug release useful for a 12-h, oral, sustained dosage form for antipyretic therapy in children, on the basis of current pediatric dosing of APAP. Coated APAP beads with the desired release rate were then developed with fluid-bed coating technology. PMID- 1403678 TI - Cholinomimetic compound distinct from caffeine contained in coffee. II: Muscarinic actions. AB - An extract with cholinergic activities was isolated from instant regular and decaffeinated coffees and purified. Intravenous injection of this cholinomimetic extract of coffee produced an abrupt depression in blood pressure and heart rate, changes that were distinct from those of known components of coffee, including caffeine, trigonelline, catechin, and chlorogenic acid. Pretreatment of the animals with naloxone, propranolol, isobutylmethylxanthine, hexamethonium bromide, and hemicholinium-3 chloride or bilateral vagotomy did not affect the cardiodepressive effects of the extract, whereas atropine completely abolished them. Direct injection of the cholinomimetic extract of coffee (20-100 micrograms) into the periaqueductal gray area of the midbrain did not produce any cardiovascular effect. However, the extract of coffee did cause relaxation of isolated rat and rabbit aortic ring preparations that were contracted under norepinephrine. The cholinomimetic extract did not inhibit purified acetylcholinesterase. This pharmacologic profile indicates that the cholinomimetic extract of coffee acts as a direct muscarinic agonist. PMID- 1403679 TI - Effect of surfactants on release of a highly water-soluble medicinal compound from an inert, heterogeneous matrix. AB - The release from a matrix compressed from a physical mixture of procaine hydrochloride, chlorinated poly(propylene), lactose, and a surfactant was investigated. With nonionic and cationic surfactants incorporated in the matrix, the release of procaine hydrochloride was linearly related to the square root of time, and as the concentration of the surfactants increased, the release was faster. When an anionic surfactant (sodium lauryl sulfate) was incorporated in the matrix, the release of procaine hydrochloride was linearly related to the square root of time; however, the release pattern depended on the concentration of the anionic surfactant. As the concentration of sodium lauryl sulfate increased to 4%, the release progressively slowed to a minimum because of the formation of a poorly soluble complex between the cationic procaine and the anionic surfactant. As the concentration of anionic surfactant increased further, the release increased as the complex was micellarly solubilized. PMID- 1403680 TI - Synthesis, cytotoxicity, hypolipidemic and anti-inflammatory activities of amine boranes and esters of boron analogues of choline and thiocholine. AB - Boron analogues of carbamoylcholine and thiocholine and esters of these analogues were prepared. These compounds were fairly stable toward hydrolysis and demonstrated moderate anti-inflammatory and hypolipidemic activities in mice. The hypolipidemic activity of the compounds at a dose of 8 mg/kg/day was equivalent in reducing lipid levels in serum to those of clofibrate at 150 mg/kg/day and lovastatin at 8 mg/kg/day. The compounds demonstrated significant cytotoxic activity against the growth of murine and human tumor cells; all were active against the growth of human HeLa-S3 uterine suspended cells, and some were active against murine L1210 lymphoid leukemia, human Tmolt3 leukemia cells, colorectal adenocarcinoma, KB nasopharynx, osteosarcoma, and glioma. These studies demonstrated that antimetabolite analogues of acetylcholine exhibit the same types of pharmacological activity as other boron-substituted betaine and amino acids. Furthermore, a strong positive correlation exists between hypolipidemic activity and cytotoxicity for these new choline derivatives, as has previously been demonstrated for other boron-containing amino acids, amides, esters, and peptides. PMID- 1403681 TI - Synthesis and pharmacological evaluation of some N [pyridyl(phenyl)carbonylamino]methyl-1,2,3,6-tetrahydropyrid ines. AB - Reaction of some picolines 5 with 1-chloro-2,4-dinitrobenzene (6) in acetone furnished methyl-substituted 2,4-dinitrophenylpyridinium chlorides 7. Further reaction with phenyl(pyridyl)carbonyl hydrazides 8 at room temperature furnished isolable 2,4-dinitroanilino derivatives 9, which were then refluxed in a water:dioxane mixture (1:4, v/v) to furnish the methyl-substituted phenyl(pyridyl)carbonyl iminopyridinium ylides 10. Reduction of the ylides with NaBH4 finally gave rise to the desired methyl-substituted phenyl(pyridyl)carbonylamino-1,2,3,6-tetrahydropyridines 11. The anti inflammatory activities of 11a-11l were determined with the carrageenan-soaked sponge model of inflammation in Sprague-Dawley rats, and the analgesic effects of these derivatives were assessed by suppression of acetic acid-induced writhing in male Swiss albino mice. All compounds tested showed moderate to good anti inflammatory and analgesic effects compared with indomethacin. Compound 11k was the most active analgesic, and 11h was the most effective anti-inflammatory agent among the methyl-substituted tetrahydropyridines. PMID- 1403682 TI - Kinetics of swelling of polymers and their gels. AB - The swelling limit or equilibrium swelling of semicrystalline or cross-linked polymers and of their gels upon immersion in liquids has been investigated extensively. Few studies, however, have dealt with the kinetics of swelling. Theoretical considerations, based on diffusion-controlled swelling, show that first-order kinetics do not apply, even though deviations during the initial and even middle stages of the swelling process may be relatively small. Extensive studies of swelling rate and equilibrium swelling of supported and unsupported gelatin films have been published. Diffusion was always fast. After it was completed, the rate of swelling was controlled by stress relaxation in the amorphous portion of the polymer network. The rate equations for this process, which also apply to regenerated cellulose, are shown to represent second-order kinetics with respect to the remaining swelling capacity. The following interpretation for the applicability of second-order kinetics to the swelling of semicrystalline polymers, such as gelatin and cellulose, is given. The rate of swelling is assumed to be directly proportional to the percent swelling capacity still available at a given time and to the total internal specific boundary area enclosing those sites capable of swelling that have not yet become hydrated and swollen at that time. The latter, in turn, is also directly proportional to the percent unrealized swelling capacity. PMID- 1403683 TI - Two-dimensional and deuterium-induced, differential-isotope-shift nuclear magnetic resonance characterization of potassium sucrose octasulfate and sucralfate. AB - Two-dimensional and deuterium-induced, differential-isotope-shift NMR measurements have made it possible to assign completely all of the 1H and 13C resonances of potassium sucrose octasulfate (K8SOS) and thereby prove complete sulfation of the sugar moiety during synthesis. In addition, a comparison of the 13C NMR chemical shifts obtained for K8SOS and sucralfate made it possible to demonstrate that the sugar moiety in sucralfate is sucrose octasulfate (SOS8-). Finally, deuterium-induced, differential-isotope-shift and 13C NMR techniques were shown to be useful tools for detecting and characterizing carbon-containing impurities and hydrolysis products in solutions containing SOS8-. PMID- 1403684 TI - Improved high-performance liquid chromatographic determination of khellin and visnagin in Ammi visnaga fruits and pharmaceutical formulations. AB - An improved, simple, selective, and sensitive reversed-phase high-performance liquid chromatographic (HPLC) assay for khellin and visnagin in Ammi visnaga L. fruits was developed by using an internal standardized technique. The HPLC column was a reversed-phase microBondapack C18 column, the mobile phase was water: methanol:acetonitrile (49:49:2), and the flow rate was 1.5 mL/min. Khellin and visnagin were detected and analyzed with a spectrophotometer set at 250 nm. Results of the HPLC analysis indicate a relative standard deviation of less than 0.04%. The analytical procedure was used for the quantification of khellin in various pharmaceutical dosage forms, such as ampules, tablets, and suppositories, with relative standard deviations of 1.2, 1.4, and 1.7%, respectively. As little as 10 ng of khellin or visnagin could be detected accurately in less than 13 min. PMID- 1403685 TI - Oxidative decarboxylation of naproxen. AB - The decarboxylation of naproxen (1H) and its salt (1-) was achieved by means of chemical [Ce(IV) or S2O8(2-)] and electrochemical oxidation. The product patterns were compatible with mechanisms involving single-electron transfer from the pi system or the carboxylate moiety. The results are discussed in connection with the involvement of electron-transfer processes in the reported phototoxicity of naproxen. PMID- 1403686 TI - Solubilization and dissolution properties of a leukotriene-D4 antagonist in micellar solutions. AB - 7-[3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propoxy]-3,4-dihydro-8- propyl-2H-1 benzopyran-2-propionic acid (1) is a leukotriene-D4 antagonist that is quite insoluble in aqueous media. Increased solubilization of 1 was achieved in micellar solutions of polysorbate 80, sodium glycocholate, sodium taurocholate, lysolecithin, and sodium taurocholate plus monoolein. The intrinsic dissolution rate of 1 was measured in the presence and absence of polysorbate 80 at pH 7.0, 8.0, and 10.0. In all the micellar solutions tested, the solubility of 1 was significantly increased. The intrinsic dissolution rate of this compound was also enhanced in micellar solutions of polysorbate 80 and with increasing values of pH. However, the magnitudes of the enhancement of the intrinsic dissolution rate were much less than expected from the enhancement of aqueous solubility. PMID- 1403687 TI - Alternative derivation for the gastrointestinal absorption residence time. PMID- 1403688 TI - A method for calculating the mean transit times and distribution rate parameters of metabolites without separate intravenous administration of metabolite. PMID- 1403689 TI - Vanadium and copper in clinical solutions of albumin and their potential to damage protein structure. AB - Solutions of albumin, for injectable use in humans, are shown to contain the transition metals vanadium, copper, and iron. Variation in the concentration of these metal ions among products from six different manufacturers suggests that problems of metal contamination arise through manufacturing processes. Vanadium concentrations correlated with the loss of tryptophan residues in albumin, whereas copper concentrations correlated with loss of thiol groups and tryptophan residues. Incubation of vanadate and cupric salts with the thiol group-containing molecules cysteine and glutathione resulted in reduction of the metal ions to lower oxidation states. Reduced forms of vanadium and copper were able to transfer electrons to molecular oxygen and produce highly reactive and damaging intermediates of oxygen, such as the hydroxyl radical. PMID- 1403690 TI - Use of fluorometry in assessing the efficacy of a cation-sensitive gel as an ophthalmic vehicle: comparison with scintigraphy. AB - Gelrite, a heteropolysaccharide that forms a gel in the presence of cations, was tested in humans for its efficacy as an ophthalmic vehicle by a nonivasive fluorometric technique. Fluorescein was used as the tracer, and its concentration in the anterior chamber was used as the principal measure of bioavailability. The gel afforded a twofold increase in penetration of fluorescein compared with an isotonic buffer solution; this increase is slightly more than can be obtained with simple viscous vehicles. The increase in penetration caused by Gelrite was confirmed by measurements of the contact time of fluorescein in the tear film with the cornea. Earlier experiments with scintigraphy suggested a considerably greater contact time of fluorescein with the cornea when Gelrite was used. However, this increased contact time may be because the technique also measures radioactive tracer that had dried out on the lid margins. Accordingly, significant quantities of fluorescein could be eluted from the lids after the penetration experiments were completed. PMID- 1403691 TI - An antidepressant principle of Lobelia inflata L. (Campanulaceae). AB - A crude methanolic extract of the leaves of Lobelia inflata exhibited antidepressant activity in mice. The extract was fractionated, monitored by the activity, to give beta-amyrin palmitate as an active component. PMID- 1403692 TI - Halogenated analogues of tamoxifen: synthesis, receptor assay, and inhibition of MCF7 cells. AB - This study was conducted to develop a ligand for imaging estrogen-receptor positive breast tumors by positron emission tomography or single photon emission computed tomography. We synthesized fluoro and iodo analogues of tamoxifen, and these halogenated analogues produced greater affinity for binding to the receptor than tamoxifen. Values of the inhibition affinity constants were as follows: tamoxifen, 15,000 nM; fluoromethyl-N,N-diethyltamoxifen, 2500 nM for the cis isomer and 500 nM for the trans isomer; and iodomethyl-N,N-diethyltamoxifen, 1500 nM for the cis isomer and 1000 nM for the trans isomer. In studies of human MCF7 breast tumor cell growth, concentrations that inhibited tumor growth in 50% of the cases were as follows: tamoxifen, 11 microM; fluoromethyl-N,N diethyltamoxifen, 4.5 and 11.8 microM for the cis and trans isomers, respectively; and iodomethyl-N,N-diethyltamoxifen, 2.4 and 6.3 microM for the cis and trans isomers, respectively. These studies suggest that both fluoro and iodo analogues of tamoxifen may be useful diagnostic compounds for predicting the response of estrogen-receptor-positive breast tumors to tamoxifen analogues used in chemotherapy. PMID- 1403693 TI - Biological activity of urease formulated in poloxamer 407 after intraperitoneal injection in the rat. AB - The advent of genetic engineering has resulted in a proliferation of protein pharmaceuticals available for a variety of therapeutic needs. However, the formulation and delivery of these proteins remain an intriguing challenge. Polymer-based protein drug delivery systems continue to be investigated, although many of the fabrication techniques used to incorporate proteins into the polymer matrix or device result in irreversible inactivation (denaturation) of the proteins. A well-characterized model enzyme, urease, was formulated in 33% (w/w) poloxamer 407 (Pluronic F-127) vehicle and injected intraperitoneally (ip) into rats in an attempt to achieve both preservation of biological activity and sustained release of the protein. The resulting ammonia concentration in plasma time profiles were compared with those for rats injected with an identical dose (27.6 units of activity per 200 g of body weight) of urease dissolved in pH 7 phosphate buffer. Neither a pH 7 phosphate buffer solution nor poloxamer 407 (33%, w/w) dissolved in pH 7 phosphate buffer, when injected ip into rats, resulted in elevated ammonia levels in plasma. The time to reach a maximum ammonia level in plasma was increased approximately threefold following the injection of the urease-poloxamer 407 formulation, compared with that in control rats administered an identical dose of urease in solution. In addition, hyperammonemia was extended almost threefold in treated rats compared with control rats, without untoward effects. However, prolonged hyperammonemia in animals receiving an ip injection of the urease-poloxamer 407 formulation may have potentially resulted from the reduced clearance of ammonia and ammonium ion in the proximal tubules of the rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403694 TI - Studies of in vitro skin permeation and retention of a leukotriene antagonist from topical vehicles with a hairless guinea pig model. AB - A leukotriene antagonist [Ro 23-3544; 6-acetyl-7-[5-(4-acetyl-3-hydroxy-2 propylphenoxy)pentyloxy] -3,4-dihydro-2H-1-benzopyran-2-carboxylic acid; 1] was studied in vitro for its permeation through and retention in hairless guinea pig skin from various topical vehicles. Both the free acid and the sodium salt forms of the drug were used. The vehicles evaluated were polyethylene glycol 400, propylene glycol, dimethyl sulfoxide (DMSO), C12-C15 alcohol lactates, dimethyl isosorbide, butyrolactone, methylpyrrolidone, hexyl laurate, isopropyl myristate, and caprylic/capric triglyceride (Neobee M5). For the salt form of the drug, the highest permeability coefficient and retention were obtained from DMSO and methylpyrrolidone, respectively. For the acid form, however, the highest permeability coefficient and retention were obtained from hexyl laurate and DMSO, respectively. The highest permeation and retention values were not obtained from the same vehicle for either the salt or the acid form of the drug. This observation questions the validity of using permeation (flux) measurements to screen topical drugs and formulations. Although the precise reasons for this lack of correlation between permeation and retention are not known at this time, this study has shown that the solubility parameters of the drug and the vehicles used may play an important role. It seems logical to conduct skin retention studies rather than flux measurements in evaluating drug delivery from dermatological products. PMID- 1403695 TI - Effect of iontophoresis on in vitro skin permeation of an analogue of growth hormone releasing factor in the hairless guinea pig model. AB - The shortened analogue of growth hormone releasing factor (GRF) Ro 23-7861 (1) has a molecular weight of 3929 daltons [equivalent to GRF (1-29)] and is more potent than the endogenous GRF (1-44). The in vitro hairless guinea pig model and vertical and horizontal diffusion cell assemblies were used to study the effect of iontophoresis on the permeability to skin of 1. The transport of 1 across the skin was studied by monitoring the rate of its appearance in the receiver compartment with a radioimmunoassay. No permeability of 1 was observed without iontophoresis, whereas with iontophoresis, the permeability of 1 was significant. For example, at a current density of 0.23 mA/cm2 and buffer concentration of 0.05 M, the flux of 1 was 56.8 +/- 8.21 ng/cm2.h. The flux of 1 was independent of the design of the permeation apparatus, the electrodes, the donor and receiver volumes, the type of current (constant or pulsed), and the frequency of the pulsed current. The flux of 1 increased curvilinearly with the increase in salt concentration of the buffer and linearly with the increase in current. PMID- 1403696 TI - Effects of enzymatic inhibition and increased paracellular shunting on transport of vasopressin analogues in the rat. AB - The Ussing chamber technique was used as an oral absorption model for studies of the relative effects of the inhibition of enzymatic degradation and increased paracellular route on the transport of the poorly absorbed vasopressin analogues lysine vasopressin (LVP) and desmopressin (DDAVP). The rates of transport of LVP or DDAVP at 250 microM across ileum and colon segments were studied in the absence and in the presence of protease inhibitors (aprotinin and bestatin) and cytochalasin-B. During the different treatments, the rates of degradation of the peptides were also studied. Detectable amounts of LVP could only be measured on the serosal side of the intestinal segment in the presence of protease inhibitors or cytochalasin-B. The treatment with cytochalasin-B increased the rates of transport of both peptides severalfold, and the effect was reversible. We suggest that the Ussing chamber technique can be used to evaluate the reasons for low transport rates across intestinal membranes. The results also show that, apart from enzymatic degradation, the vasopressin analogues LVP and DDAVP have additional permeation problems; therefore, it may be necessary to increase the paracellular route to increase the absorption of these peptides. PMID- 1403697 TI - Preparation of potential anti-inflammatory agents from dehydroabietic acid. AB - Methyl 16-nor-16-carboxydehydroabietate (22), 16-nor-16-carboxydehydroabietinol acetate (23), methyl 7-keto-16-nor-16-carboxydehydroabietate (29), 16-nor-16 carboxydehydroabietic acid (30), 16-nor-16-carboxydehydroabietinol (31), 7-keto 16-nor-16-carboxydehydroabietic acid (32), methyl 7-hydroxy-16-nor-16 carboxydehydroabietate (33), and 7-hydroxy-16-nor-16-carboxydehydroabietic acid (34) were prepared from dehydroabietic acid. Only 22 and 32 had weak anti inflammatory activity. PMID- 1403698 TI - Kinetics and mechanism of chlorine exchange between chloramine-T and secondary amines. AB - The kinetics and mechanisms of chlorine transfer from chloramine-T (CAT) to several amines are second order and independent of p-toluenesulfonamide concentration; thus, the reaction does not involve disproportionation of CAT to dichloramine-T. From the profile of pH versus rate, the following mechanisms were proposed: (1) reaction of the ionized species of CAT with the ionized amine (ionic mechanism) and (2) reaction of the un-ionized species of CAT with the un ionized amine (nonionic mechanism). The second-order, pH-independent rate constants calculated for the ionic and nonionic mechanisms were 1.6 and 5 x 10(6) M-1 s-1, respectively. Although these two mechanisms are kinetically indistinguishable, the rate constant for the nonionic mechanism is of the same order of magnitude as those calculated for similar chlorination reactions involving nonionizable chloramines, such as N-chlorosuccinimide, N chloroquinuclidine, and N-chloro-N-methylbenzenesulfonamide. The proposed mechanism for the chlorine exchange involves a molecule of water in a cyclic, six membered transition state. PMID- 1403699 TI - Structure-activity considerations in kinetics and mechanism of chlorine exchange between chloramine-T and secondary amines. AB - To study the mechanism of N-chlorination of secondary amines by chloramine-T, the kinetics of the reactions of some aromatic-substituted analogues of N chlorobenzenesulfonamide with various secondary amines were determined. The importance of amine basicity and reactivity of the N-Cl bond of the N chlorobenzenesulfonamide was also assessed. The results indicate that a mechanism involving the un-ionized species of both reactants (i.e., a molecular mechanism), rather than an ionic mechanism, is operating and that the reaction most likely proceeds via a six-membered-ring transition state that incorporates a water molecule. PMID- 1403700 TI - Determination of a cephalosporin antibiotic, ceftibuten, in human plasma with column-switching high-performance liquid chromatography with ultraviolet detection. AB - A column-switching high-performance liquid chromatographic assay combined with a heart-cutting technique and UV detection (LC/LC/UV) was developed to determine ceftibuten, a new oral cephalosporin, in human plasma. Plasma samples were directly injected into the first chromatographic column for sample cleanup and extraction. Thereafter, a switching valve, located at the junction of the first cleanup column and the second analytical column, opened during a 4-6-min interval after injection to transfer the segment containing ceftibuten into the analytical column for quantitation. The method was used routinely in pharmacokinetic studies and has the advantages of simplicity, improved sensitivity, and selectivity. Concentrations of ceftibuten in plasma over a range of 0.1-20 micrograms/mL can be determined with high precision and reproducibility. A single, oral, 200-mg dose of ceftibuten in humans resulted in a maximum concentration of 9.79 micrograms/mL, an area under the plot of concentration of drug in plasma versus time (0-12 h) of 47.77 micrograms.h/mL, and a half-life of 3.2 h. These results document the utility of the LC/LC/UV method in clinical pharmacokinetic studies. PMID- 1403701 TI - Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. II: Applications of equation to optimize tableting conditions. AB - In a companion communication, an equation (eq 1) of the homogeneity of binary random mixtures, which applies to constituents differing in particle size and in bulk density, was derived. The present paper demonstrates the practical applications of this equation in optimizing tableting conditions with respect to a high dose uniformity. Tablets of 50:50 (w/w) mixtures of coarse sucrose and of fine microcrystalline cellulose (Avicel PH 101)-talc vehicle were produced on a single-punch machine. Without a spin feeder, the tablets showed variations in content uniformity that were significantly higher than those estimated from eq 1. Correlation analysis between the individual mass and the content of the constituents of the tablets revealed this difference to be due to nonuniformity of the die filling and not due to incomplete mixing. Accordingly, the use of a spin feeder allowed production of tablets with higher dose uniformity, which conformed well with the theoretical optimum predicted with eq 1. Further variation of the processing conditions cannot improve the quality (i.e., varying the tableting speed resulted in equal or in poorer uniformity of dose content). PMID- 1403702 TI - Factors affecting iontophoretic mobility of metoprolol. AB - The effect of different factors on the iontophoretic transport of metoprolol was analyzed. In vitro experiments were first performed in a diffusion cell with a cellophane membrane. Comparison of different pH, buffers, and ionic strengths in the donor compartment showed that higher iontophoretic transport was obtained with phthalate buffer (0.01 M) at pH 3. When the current density increased, the flux of metoprolol also increased. A decrease in drug concentration or an increase in viscosity slowed down the iontophoretic transport of metoprolol. The fluxes of metoprolol through hairless rat skin were strongly enhanced compared with passive diffusion. Direct current seemed to be more efficient than pulse current. When the on:off ratio of the pulse current was reduced, the flux also decreased. PMID- 1403703 TI - A kinetic and mechanistic study of the hydrolysis of camptothecin and some analogues. AB - Quantitative rate and equilibrium constants for the hydrolysis of the lactone (ring E) in camptothecin (1) and analogues (2-5, all substituted in the A ring of 1) at 25 degrees C in aqueous solution were determined by high-performance liquid chromatography with UV-visible detection and by UV-visible spectrophotometry. It was shown that the lactone was converted to the carboxylate in a pH-dependent equilibrium. No major differences were observed in rate and equilibrium constants for 1-5, a result suggesting that the mechanism of lactone hydrolysis is independent of a variety of substituents on the A ring. The conversion of the lactone to its carboxylate form occurred under neutral and basic conditions and appeared to be largely dependent on hydroxide ion. The conversion of the carboxylate to the lactone was observed under neutral and acidic conditions and was pH independent at pH values greater than 5 and dependent on hydronium ion at pH values less than 5. Significant incorporation of oxygen-18 into the lactone ring of 3, a water-soluble analogue of 1, was observed for the ring opening and subsequent ring closing of 3 in H2(18)O. This finding strongly suggests that the mechanism of lactone ring hydrolysis involved acyl cleavage rather than alkyl cleavage. Kinetic solvent isotope effects (kH2O/kD2O, where kH2O and kD2O are the rate constants in H2O and D2O, respectively), obtained over the pH-rate profile for 1, were used to speculate about the nature of the transition states involved in the opening and closing reactions of the lactone ring. PMID- 1403704 TI - Improvements in solubility and stability of thalidomide upon complexation with hydroxypropyl-beta-cyclodextrin. AB - Thalidomide is in clinical use for the treatment of graft-versus-host disease in leukemia patients after bone marrow transplant. Low levels of the drug in plasma after oral administration have made an intravenous thalidomide formulation desirable. Thalidomide, however, is sparingly soluble in aqueous solution (50 micrograms/mL) and unstable. Complexation with hydroxypropyl-beta-cyclodextrin has significantly improved the aqueous solubility and stability of thalidomide. Results obtained with HPLC and 1H NMR spectrometry have demonstrated that the solubility is increased to 1.7 mg/mL and the half-life of a diluted solution is extended from 2.1 to 4.1 h. Hence, an intravenous thalidomide-hydroxypropyl- beta cyclodextrin solution has the potential to significantly improve current therapy for graft-versus-host disease by providing sustained high levels of drug in the plasma. PMID- 1403705 TI - A high-performance liquid chromatographic assay for dideoxyinosine in monkey plasma and urine. AB - A simple, reliable, reproducible, rapid, and sensitive method for high performance liquid chromatographic assay of dideoxyinosine (DDI) in macaque plasma and urine is described. The method is capable of detecting 25 ng of DDI on column. PMID- 1403706 TI - Qualitative analysis of the stability of the oxazine ring of various benzoxazine and pyridooxazine derivatives with proton nuclear magnetic resonance spectroscopy. AB - A series of 3,4-dihydro-1,3-benzoxazine and 3,4-dihydro-1,3-pyridooxazine derivatives was synthesized, and the hydrolysis of the derivatives was studied with proton nuclear magnetic resonance spectroscopy. The oxazine derivatives underwent various degrees of hydrolysis when H2O was added to dimethyl sulfoxide solutions of the compounds. The rates and extents of decomposition of the oxazine ring systems depended on the electronic effects of substituents within the molecules. Examination of the proton nuclear magnetic resonance spectra that were generated during decomposition of the oxazines and trends in stability of the oxazine derivatives suggest the formation of an intermediate in the hydrolysis mechanism. PMID- 1403707 TI - Protection against chronic gastric ulceration in the rat with sulfhydryl containing agents. AB - Reserpine (intraperitoneal, 5 mg/kg every day for 5 days) produced chronic ulceration of the rat stomach 2 weeks postdose. Gavage with 1% DL-cysteine or DL methionine-S-methylsulfonium chloride at 1 mL/day for 2 weeks and 5 days protected against ulceration in 30% of the rats, and this protection extended to 80% of cases with 2% solutions. Similar gavage with 5% solutions protected all rats against ulceration without significantly influencing the basal H+ output [13.1 +/- 0.3 and 14.2 +/- 0.2 mumol for DL-cysteine and DL-methionine-S methylsulfonium chloride, respectively, versus 15.1 +/- 0.4 mumol (mean +/- standard error of the mean; n = 10)]; that is, cytoprotection was achieved. PMID- 1403708 TI - Predicting the postconsolidation relaxation behavior of sodium chloride tablets. AB - A model that relates the interparticulate contact stress within a tablet matrix with the compaction stress has been developed. The model permits the application of nonlinear deformation kinetic analysis to quantification of the viscoelastic behavior of tablet constituents. Deformation kinetic analysis assumes that stress relaxation is controlled by thermally activated processes similar in character to those associated with chemical reaction kinetics. The model was tested by measuring the stress relaxation of sodium chloride compacts as a function of temperature and relative density. The experimental activation parameters agree with literature values within experimental errors. PMID- 1403709 TI - Alkaline hydrolysis of oligomers of tartrate esters: effect of a neighboring carboxyl on the reactivity of ester groups. AB - The importance and the effect of neighboring groups on the hydrolysis of polymeric esters were demonstrated. Several oligomers of poly(butylene tartrate) were synthesized, and their kinetic behavior was studied under alkaline conditions. The oligomers and their degradation products were monitored by HPLC and identified by fast atom bombardment mass spectrometry. The rates of hydrolysis measured at pH 5-8 and at 75 degrees C indicate that the degradation of the oligomers obeyed pseudo-first-order kinetics. The rate of hydrolysis among the homologous series of oligomers increased as the molecular weight increased. However, the increase in hydrolysis rate was not proportional to the number of ester linkages in the oligomers. This deviation was explained on the basis of electrostatic repulsion of the neighboring carboxylate group toward the hydroxide ion. The calculations revealed that the electrostatic effect was so great that the ester linkage adjacent to the carboxylate anion did not contribute to the overall rate of hydrolysis. The technique presented here can be extended to any multifunctional-group compound that has repeat units and can undergo a specific reaction that can be accurately measured. PMID- 1403710 TI - High-performance frontal analysis-high-performance liquid chromatographic system for stereoselective determination of unbound ketoprofen enantiomers in plasma after direct sample injection. AB - An on-line, high-performance frontal analysis (HPFA)-high-performance liquid chromatographic system was developed for the enantioselective determination of a low level of unbound ketoprofen (KP) that is in equilibrium with KP that is bound to protein. The system consists of three subsystems (HPFA system, preconcentration system, and chiral separation system) connected in series in the stated order via column-switching valves. When either a 300-microL portion of buffer solution containing 300 or 550 microM human serum albumin and 100 or 300 microM racemic KP or a 300-microL portion of human plasma containing 12.5-100 microM racemic KP was directly injected onto the HPFA column with the mobile phase at a low flow rate, KP was separated from proteins and eluted as a zonal peak with a plateau. The KP concentration in the eluant of the plateau region was the same as the unbound-KP concentration that was in equilibrium with protein bound KP in the initial sample solution. A 1-mL portion of the eluant of the plateau region was switched to the preconcentration system, where KP was adsorbed and condensed on an octadecylsilyl silica (ODS) column. The adsorbed KP was eluted out of the ODS column and transferred to the chiral separation system, via another switching valve, where the enantiomers of unbound KP were separated and determined. The results agree well with those obtained by the conventional ultrafiltration method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403711 TI - Carbonic anhydrase inhibitors. V: Pyrylium salts in the synthesis of isozyme specific inhibitors. AB - Syntheses and physicochemical properties of 2,4,6-tri-, 2,3,4,6-tetra-, or 2,3,4,5,6-pentasubstituted 1-(2-sulfonamido-1,3,4-thiadiazol-5-yl)pyridinium perchlorates are presented. The new compounds, putative inhibitors of membrane bound carbonic anhydrase, were tested for inhibitory action on the bovine red cell enzyme. PMID- 1403712 TI - Partition behavior of anilines in bulk-phase and high-performance liquid chromatographic systems: influence on correlation with biological constants. AB - The partition behavior of a mixed series of ring-substituted anilines in reversed phase high-performance liquid chromatographic systems is substantially different from that observed in a classical bulk-phase partition system with n-heptane as the aprotic reference solvent. On the basis of the equivalence of each ring substituent in the p-straight-chain methylene groups (v value) as a function of the fraction of organic solvent (acetonitrile or methanol) in the mobile phase, the biased partition behavior for imperfect homologues and heterologues is verified relative to that of perfect homologues. This behavior was tentatively attributed, mainly, to differences in the hydrogen bonding capacity of the compounds, which is associated with the electronic character of the working solvent. These differences cannot be normalized through the use of extrapolated initial partition coefficient (K'o) values because of carryover effects of the solvent. When the chromatographic partition constants (K') and K'o are used, correlations with previously determined intestinal absorption rate constants are definitely worse than the correlations with the reference n-heptane partition coefficients. Possible implications of these observations on lipophilicity biological activity correlations are briefly discussed. PMID- 1403713 TI - Basic cholane derivatives. XI: Comparison between acid and basic derivatives. AB - A series of hydroxycholan-24-amines was synthesized; the carboxyl group of starting unconjugated bile acids was transformed into a basic moiety [-NH2, NHCH3, -N(CH3)2, or -NHCH2C6H5] at C-24. Solubilities, acidities, partition coefficients, and critical micellar concentrations were measured and compared with those of the corresponding bile acids. Because the steroid nucleus in the amines is the same as that in the bile acids, most of the physical-chemical properties of the two compound classes were similar. The amines were more soluble than the corresponding acids; solubilities depended mainly on the number of steroid hydroxyls and, to a lesser extent, on the side chain. Amines are strong bases in water, whereas unconjugated bile acids can be classified as weak acids. N-Benzylamino derivatives have higher log P (P is partition coefficient) values, as a consequence of the bulky hydrophobic substituent; the log P values were almost the same for the amines and the bile acids and depended on the steroid hydroxyls. Amines can self-aggregate at an acidic pH and form cationic micelles; the critical micellar concentrations of amines were of the same order of magnitude as those of bile acids. The introduction of a basic function in the side chain of the cholane moiety increased the antimicrobial activity toward most gram-positive strains. PMID- 1403714 TI - Peptide stability in drug development: a comparison of peptide reactivity in different biological media. AB - Degradation kinetics for several peptides that bind to the major histocompatibility complex on antigen-presenting cells were determined in both human serum (HS; 25%) and synovial fluid (SF; 25%) from patients with rheumatoid arthritis to test whether therapeutic intervention of rheumatoid arthritis by direct intrasynovial injection is feasible (at least in terms of peptide stability). Controls consisted of enzymatically immature 10% fetal calf serum and peptidase-rich 5% liver homogenate (all diluted with RPMI-1040 tissue culture medium). Peptide half-lives ranged from approximately 4 to greater than 10,000 min, with most peptides showing half-lives of approximately 10-100 min. These studies show that, even though the populations of inflammatory and other cell types in SF and HS are different (and may, therefore, generate different peptidase profiles), the observed peptide stabilities in SF and HS are similar. This finding indicates that the effect of SF on peptide stability is similar to that of HS. PMID- 1403715 TI - Drug and vehicle deposition from topical applications: use of in vitro mass balance technique with minoxidil solutions. AB - The disposition of minoxidil and propylene glycol from topical solutions was measured by using an in vitro mass balance technique. The experimental approach included assessment of the following compartments of the skin and the diffusion cell as a function of time: (1) donor compartment; (2) hairless mouse skin surface, epidermis, and dermis; and (3) receiver compartment. Excellent mass balance was achieved for minoxidil at three doses. However, the recovery of propylene glycol depended on both application volume and time. The experiment involving the evaporation of propylene glycol and water from the propylene glycol:ethanol:water (20:60:20, v/v) mixture, which was placed in the well of a tissue culture plate at room temperature and 37 degrees C, substantiated the loss of vehicles to the air. When a thin application of 20 microL/cm2 was used, 60% of the propylene glycol was unaccounted for after 16 h. The evaporation of propylene glycol concentrated the solution to supersaturation, precipitated out the drug, and then stabilized the thermodynamic activity of the drug in the vehicle. The amount of formulation applied influences the rate of concentration and, thus, the time at which minoxidil precipitates. The precipitation limits the amount of minoxidil that can be absorbed and leads to poor percutaneous absorption of drug from the formulation. PMID- 1403716 TI - In vitro percutaneous absorption of thiamine disulfide from a mixture of propylene glycol and fatty acid. AB - The in vitro percutaneous transport of thiamine disulfide (TDS), an oxidized dimer of thiamine, from propylene glycol through excised abdominal rat skin was studied. The application of saturated, long-chain fatty acids [stearic acid (18:0), myristic acid (14:0), and lauric acid (12:0)] as enhancers to the system was also studied. TDS permeated through rat skin from propylene glycol with a flux of 2.5 +/- 0.8 micrograms/cm2/min. The flux was enhanced 31 times by 12:0 and 1.4 times by 14:0 and was suppressed to 80% of its original value by 18:0. The absorption of TDS could not be explained by TDS permeating across a dialysis membrane, but the interaction between TDS and fatty acids may influence the system. The results show the possibility of developing a transdermal thiamine delivery system. PMID- 1403717 TI - Stereoselective urinary pharmacokinetics of dl-threo-methylphenidate and its major metabolite in humans. AB - Stereoselective urinary pharmacokinetics of dl-threo-methylphenidate (MPH) and its major metabolite, dl-ritalinic acid (RA), were examined in a cohort of healthy subjects. On two occasions, separated by one week, each subject received MPH.HCl either intravenously (10 mg) or orally (40 mg). Urine was collected in six time segments, up to 16 h after each dosing. In the first 2 h after oral administration of MPH, d-MPH found in the urine was 10-fold greater than the l antipode, whereas there was no significant difference between the amounts of MPH enantiomers excreted after the intravenous dose. Examination of RA content in the 0-2-h urine samples after oral administration of MPH indicated the presence of higher levels of l-RA (d-RA:l-RA, 0.37), whereas after intravenous MPH, there was no significant difference between the amounts of RA enantiomers. Moreover, after oral administration of MPH, the ratio of d-MPH to l-MPH was approximately 10 in urine samples from each of the time segments. By contrast, after intravenous administration of MPH, the d:l ratio changed progressively from 1.16 in the 0-2-h urine sample to 9.06 in the 12-16-h sample. These observations suggest that, after oral administration of dl-MPH, the distortion in the ratio of MPH or RA enantiomers in urine samples was attributable to enantioselective presystemic conversion of MPH to RA rather than to enantioselective excretion. PMID- 1403718 TI - Nasal delivery of [14C]dextromethorphan hydrochloride in rats: levels in plasma and brain. AB - Dextromethorphan (DM) is a neuroprotective agent. The mechanism of action is believed to be by N-methyl-D-aspartate receptor blockade. The concentration of DM in the brain is believed to be dose and route dependent. Delivery by the nasal route has received a lot of attention recently, because drug absorption from this route follows intravenous profiles with no first-pass effect. The uptake of DM in the brain from the nasal route was 65.9% compared with the intravenous route, whereas the plasma bioavailability from the nasal route was 78.8%. The nasal route is a viable alternative to the parenteral route for DM administration. PMID- 1403719 TI - Pulmonary deposition of inhaled terbutaline: comparison of scanning gamma camera and urinary excretion methods. AB - Deposition from a multidose powder inhaler (Turbuhaler, Astra) delivering 500 micrograms of terbutaline sulfate per metered dose was compared by two techniques in a group of six healthy volunteers. The deposition of the radionuclide 99mTc, which was used to label terbutaline sulfate powder, was quantified by gamma camera (G-method). Simultaneously, the gastrointestinal absorption of swallowed drug was blocked with activated charcoal, and the amount of terbutaline in a urine sample, collected over a period of 48 h and corrected by a pharmacokinetic internal standard of intravenous deuterated terbutaline, was used as a measure of lung deposition (U-method). The mean (standard deviation) depositions in lung were 26.9 (3.8%) of the dose for the G-method and 21.1 (3.2)% of the dose for the U-method. Possible reasons for the differences between the two means are discussed. Both methods are suitable for assessing deposition from medical aerosol inhalers; the U-method requires access to gas chromatography-mass spectrometric equipment, and the G-method requires access to gamma camera facilities. PMID- 1403720 TI - Complexation of steroid hormones with cyclodextrin derivatives: substituent effects of the guest molecule on solubility and stability in aqueous solution. AB - The inclusion complexation of homologous derivatives of steroid hormones with cyclodextrins and 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) was investigated with regard to underlying structure-interaction relationship. The interaction was studied by phase solubility analysis and stabilization effects of complex formation with 2-HP-beta-CD. The solubilizing and stabilizing abilities of 2-HP-beta-CD were generally more effective for testosterone derivatives than for estradiol esters. Within a homologous series of steroid hormones, the steepest linear solubility isotherms were found for 17-methyl and 3-methyl derivatives. The solubilization of steroid esters by 2-HP-beta-CD depended on the structure and length of the ester side chain. The interaction of 2-HP-beta-CD with the steroids was hindered by long-chain fatty acid ester groups. With increasing length of the side chain, a decline of the isotherms occurred and the phase solubility behavior changed from linear to exponential. Contrary to expectations, benzoylation of steroids considerably decreased the guest-host interaction. The observed rates of degradation of the steroid esters were significantly reduced by 2-HP-beta-CD, depending on the chain length, and correlated well with the order found in phase solubility analysis. The degradation showed no deviations from pseudo-first-order kinetics, and the degradation mechanism was not changed because of complexation. The results suggest that interaction of 2-HP-beta-CD with steroid esters involves the ester functions of the prodrugs and is more suitable for unsubstituted guest molecules. PMID- 1403721 TI - Pharmacokinetics of diazepam in the rat: influence of a carbon tetrachloride induced hepatic injury. AB - The pharmacokinetics of diazepam in normal rats and in rats pretreated with carbon tetrachloride to induce hepatic cirrhosis (cirrhotic rats) was studied after intravenous and oral administration of the drug (4 mg/kg). Animals pretreated with this hepatotoxic agent showed a significant prolongation in the half-life of diazepam in plasma that is due more to an increase in volume of distribution rather than to a decrease in clearance. This study confirmed that diazepam was highly extracted by the rat liver and was not affected by the hepatotoxic agent, although there probably was a saturation of the activity of the cytochrome P450 enzyme when the drug was administered orally. Diazepam binds to plasma proteins to a high degree in both normal and cirrhotic rats; however, in the latter, a significant increase in the fraction of unbound drug in plasma was observed. Pretreatment of rats with carbon tetrachloride did not produce any change either in the distribution of diazepam into erythrocytes or in the disposition of the metabolite desmethyldiazepam. PMID- 1403722 TI - Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. III: Range of validity of equation. AB - The validity of an equation developed to determine the quality of binary random mixtures (eq 1) was evaluated with tablets prepared from random mixtures of a coarse constituent A (sucrose) and fine constituent B [microcrystalline cellulose (Avicel PH 101)-talc] with the A:B ratios (w/w) varying from 10:90 to 80:20. With all A:B ratios, superior agreement was established between the random content variations determined with eq 1 and the content variations found in the tablets. The 80:20 ratio, however, was just at the boundary, and random quality was achieved with the 50-mg tablets but not with the 200-mg tablets because of segregation. From percolation theory, this result is a consequence of the small proportion by volume (bv) of B that is almost equal to the precolation threshold (Pcb) of B of 0.3. With bv less than Pcb, the fine constituent B does not form a coherent lattice, and eq 1 is no longer valid. To estimate the volume proportions av and bv from the mass proportions a and b, two methods were established. Method 1 assumed the bulk densities of A and B to be representative and was used when av was higher than the percolation threshold (Pca) of A of 0.3 (a, 0.5). Method 2 used the true particle density of A and was valid with av values of less than 0.1 (a, 0.3), in which case the particles of A were dispersed as individuals in the matrix of B. PMID- 1403723 TI - Physicochemical characterization of a model intravenous oil-in-water emulsion. AB - Photon correlation spectroscopy, nuclear magnetic resonance spectroscopy, electron microscopy, and small-angle X-ray scattering were used for the structural characterization of a model oil-in-water emulsion containing particles in the submicrometer size range. Additionally, small-angle X-ray diffraction, wide-angle X-ray diffraction, and differential scanning calorimetry were applied to raw materials and to binary mixtures. The majority of emulsion droplets have the characteristic of an ideal emulsion droplet, that is, a liquid lipid core covered by an emulsifier monolayer. However, the system contains a certain excess of emulsifier. Particles with bi- and/or oligolayer structures can be deduced. Double-emulsion droplets were detected. Large unilamellar vesicles were not found; however, the existence of small unilamellar liposomes (also referred to as small unilamellar vesicles or SUVs) seems likely. The proportion of all small nonmonolayer structures was quantified by nuclear magnetic resonance spectroscopy. No mixed micellar structures were detectable. Lysophospholipids were not detected in the aqueous phase, indicating their predominant incorporation into the emulsifier layers. Water-soluble phospholipid degradation products were found in the water phase. The existence of at least several monolayers of phospholipids does not seem to be a prerequisite for a stable soybean oil-in-water emulsion, in general. PMID- 1403724 TI - Influence of dielectric constant on sedimentation rate of concentrated suspensions of aluminum and magnesium hydroxides. AB - Sedimentation of dilute pharmaceutical suspensions obeys Stokes's law, which assumes that there is no interaction between particles. The behavior of concentrated pharmaceutical suspensions is generally interpreted by use of modifications of Stokes's law that do not consider chemical interaction between particles. Properties of the medium itself, such as dielectric constant and surface tension, have not been included in the established equations. The present work shows that the dielectric constant of the medium has a distinct effect on the rate of sedimentation of the systems investigated. PMID- 1403725 TI - Quantitative structure-activity relationship study of the biophysicochemical behavior of nitrosamine. AB - The partition coefficients of 14 aliphatic nitrosamines were measured in six water-organic solvent systems. Correlations between Hansch's hydrophobic parameter (pi) and Kier and Hall's topological index (1 chi) allowed pi to be substituted by 1 chi in the structure-activity correlations of the carcinogenicity data of the nitrosamines studied. The use of high-performance liquid chromatographic capacity factors of nitrosamines in these correlations is also discussed. PMID- 1403726 TI - Metabolism and distribution of 1-[14C]alprazolam in rats. AB - Using 14C-labeled alprazolam (1-[14C]APZ) as a model for 1-[11C]APZ, we evaluated the tissue distribution of total radioactivity and assessed the contribution of the polar metabolites of APZ (alpha-hydroxymethyl- and 4-hydroxy-APZ) to radioactivity levels in the plasma and brains of rats over the course of 1 h. The biodistribution data showed that the uptake of radioactivity by rat brain was 0.31% of the injected dose per gram of tissue weight at 10 min postinjection. Pretreating rats reduced the levels in brain to 0.21% of the injected dose at 10 min but had little effect on the distribution of radioactivity in plasma and other tissues studied. Analysis of the metabolites in plasma and brain homogenates by an extraction-thin-layer chromatography-liquid scintillation method revealed that greater than 94% of the radioactivity in the rat brain was due to 1-[14C]APZ over the course of 1 h. APZ, therefore, is stable to metabolic transformations in the rat brain, and the polar metabolites are readily conjugated and excreted so that their cerebral uptake is minimal. PMID- 1403727 TI - Adaptive computer program for determination of absorption profiles by numerical deconvolution: application to amoxicillin absorption. AB - We have developed a specific numerical deconvolution program for the Apple Macintosh microcomputer. After comparison with other methods, we used the program to evaluate the influence of nifedipine on the absorption and bioavailability of amoxicillin. The technique provided a model-independent approach. This study shows that the simultaneous administration of nifedipine with amoxicillin leads to a significant increase in both the total quantity of amoxicillin absorbed (+22%) and the rate of absorption. Parameters of clearance, volume of distribution, and elimination were unaffected. Numerical deconvolution analysis showed that nifedipine did not modify the absorption kinetics of amoxicillin, which are characterized by a lag time followed by a constant rate of absorption, suggesting zero-order kinetics with first-order kinetics at the end of the process. The results suggest the existence of a specialized, saturable transport molecule for this antibiotic. PMID- 1403728 TI - In vitro and in vivo release of poly(DL-lactic acid) microspheres containing neurotensin analogue prepared by novel oil-in-water solvent evaporation method. AB - Poly(DL-lactic acid) (PLA) microspheres containing a neurotensin analogue [NA; H(CH3)-Arg-Lys-Pro-Trp-tert-Leu-Leu-OEt.3HCl] were prepared by a novel oil-in water (o/w) solvent evaporation method, and the release behaviors were evaluated in vitro. About 20% of the loaded NA was released initially, and the subsequent release lasted for a month from microspheres prepared with PLA of molecular weight 2000 (PLA 2000). A smaller initial release from PLA 4000 and PLA 6000 microspheres was found, but a lag time of 2-3 weeks during which the drug was not released was observed with PLA 4000 and PLA 6000 microspheres. The addition of relatively hydrophilic monoglycerides decreased the lag time, and a fairly constant release of NA was achieved. The pharmacokinetic behavior of NA from PLA 2000 microspheres was studied in rats. The release of the drug after a subcutaneous injection exhibited pseudo-zero-order kinetics for 1 month. The initial release of the drug from the microspheres was reflected in a sharp increase of the plasma levels of the de-ester form of NA [H(CH3)-Arg-Lys-Pro-Trp tert-Leu-Leu-OH], and the subsequent steady-state levels agreed well with the predicted levels obtained from analysis of constant-infusion kinetics. PMID- 1403729 TI - Synthesis and biological activity of new 1,8-diaza-2,9,10-anthracenetrione derivatives. AB - Diels-Alder heterocycloaddition reactions of 2,5,8-quinolinetriones and 1 azadienes afford 1,8-diaza-2,9,10-anthracenetriones, which are simple analogues of the antitumoral antibiotic diazaquinomicin A. Cytotoxicity in this series and antitumor activity of the lead compound, 6-methyl-1,8-diaza-2,9,10 anthracenetrione, are reported. PMID- 1403730 TI - Prominent inclusion effect of dimethyl-beta-cyclodextrin on photoisomerization of the thromboxane synthetase inhibitor (E)-4-(1-imidazoylmethyl)cinnamic acid. AB - The direct photoisomerization of (E)-4-(1-imidazoylmethyl)-cinnamic acid (IMC), a thromboxane synthetase inhibitor, to its (Z)-isomer at pH 2.0 was decelerated by beta-cyclodextrin (beta-CyD) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM beta-CyD). The photostationary composition [(Z)-isomer:IMC ratio] was shifted in favor of IMC. These effects were much greater with DM-beta-CyD than with the parent beta-CyD. The quantum yield of the photoisomerization was significantly decreased by complex formation with beta-CyDs, whereas the extinction coefficient of the guest was only slightly decreased. This situation was in sharp contrast to those observed in less polar solvents and suggests that the suppressing mechanism with beta-CyD is different from that with less polar solvent systems. Spectroscopic studies (ultraviolet, circular dichroism, and nuclear magnetic resonance) indicated that IMC is tightly included in an axial mode in the cavity of DM-beta-CyD and that the rotation of the photoreactive site is sterically hindered. The results suggest that the suppressing effect of beta-CyDs on the photoisomerization of IMC results mainly from a steric origin. PMID- 1403731 TI - Interaction of bovine serum albumin with the surface of a microcrystalline aluminum oxide hydroxide compound: a possible new type of phosphate adsorbent. AB - Aluminum hydroxide gel (ALG) has been effective for ameliorating acidosis associated with phosphatemia caused by hemodialysis. However, aluminum accumulation in the body causes severe side effects. As substitute for ALG, a new type of aluminum oxide hydroxide (tentatively named PT-A) was prepared with the hope of future clinical use. PT-A has a microcrystalline structure with a high resistance to pH change and has more phosphate-binding efficacy than ALG. It was tested for possible interaction with protein by adsorption test, zeta-potential analysis, X-ray diffraction, and scanning electron microscopy. Bovine serum albumin (BSA) was chosen as a model protein. The interaction of BSA with PT-A depended on the amount of adsorbent. Protein adsorption occurred rapidly and reached the maximal level at near neutral pHs. Phosphate adsorption was not affected by the presence of BSA, but the interaction of BSA with PT-A was significantly reduced by the presence of phosphate. Zeta-potential changes on the surface of PT-A indicated that the positively charged surface of PT-A was covered with negatively charged phosphate ions that repelled negatively charged BSA molecules. X-ray diffraction patterns indicated no observable structural alteration caused by adsorption of BSA or phosphate, and scanning electron microscopy revealed that BSA covered the outer surface of PT-A but did not cover small pores, where phosphate can freely penetrate. PMID- 1403732 TI - Spectrofluorimetric study of the binding of 1-anilinonaphthalene-8-sulfonate to bovine serum albumin. AB - We studied the binding of the fluorescent probe 1-anilinonaphthalene-8- sulfonate to bovine serum albumin by spectrofluorimetric techniques. The binding of this probe to bovine serum albumin was via two types of sites: one with a high affinity constant but relatively fewer in number and the other with a lower affinity constant but greater in number. The number of binding sites of each type of site and their respective association constants varied with the features of the moiety and the temperature. The results indicate that the simplistic interpretation involving a single type of interaction of hydrophobic nature can no longer be supported and that additional involvement of other, nonhydrophobic types of binding should be considered. This thermodynamic study allowed calculation of changes in enthalpy, Gibbs free energy, and entropy values that are consistent with this hypothesis. PMID- 1403733 TI - Lipidic peptides. V: Penicillin and cephalosporin acid conjugates with increased lipophilic character. AB - Lipophilic, double-ester derivatives of beta-lactam antibiotics with methylene, ethylene, and propylene spacers were prepared by crown-ether-assisted coupling of halogenoalkyl esters of 2-(tert-butoxycarbonylamino)decanoic acid to either penicillin G or cefuroxime. The hydroxyethyl ester of penicillin G and the tert butoxypropyl ester of cefuroxime were also prepared. The lipophilic, double-ester conjugates, the hydroxyethyl ester of penicillin G, and the tert-butoxypropyl ester of cefuroxime showed weak or no antibiotic activity in vitro, as expected. The lipophilic penicillin G conjugates and the tert-butoxypropyl ester of cefuroxime were active in vivo against a nonpenicillinase-producing strain of Staphylococcus aureus after subcutaneous administration. The penicillin G double ester with propylene spacer and the tert-butoxypropyl ester of cefuroxime were inactive in vitro, a fact indicating that both compounds were hydrolyzed in vivo, as desired. After oral administration, the lipophilic, double-ester conjugate of penicillin G with methylene spacer and the tert-butoxypropyl ester of cefuroxime were active. PMID- 1403734 TI - Talectomy for diabetic Charcot foot. An alternative to amputation. AB - A talectomy was performed because of Charcot degeneration during recovery from a hallux amputation. The patient was treated conservatively but Charcot degeneration continued, resulting in ulceration and dorsomedial dislocation of the talar head. The patient was hospitalized, and the talectomy was performed. The patient returned to normal activities. PMID- 1403735 TI - Surgical repair of a talar body nonunion. AB - Fractures of the talus are significant injuries and are usually intra-articular. The authors discuss the evaluation and management of a patient with a delayed union of a talar body fracture. Assessment of talar vascularity and joint integrity should be performed preoperatively. The role of internal fixation and continuous passive motion is discussed. PMID- 1403736 TI - Coumadin skin necrosis. Pedal manifestations. AB - The idiosyncratic dermatologic reaction to coumarin-like agents, most notably, Coumadin (warfarin sodium) has been well described in the world's literature. Although the incidence is reported to be less than 0.1% of patients treated with Coumadin, pedal cases tend to be striking and their treatment seemingly tenuous. PMID- 1403737 TI - Cystic bone lesion in the fifth metatarsal with subcutaneous rheumatoid nodule. PMID- 1403738 TI - Bilateral bipartite medial cuneiform. A case report. AB - A fracture to the intermediate cuneiform that was not definitively detected on routine radiographs because of the overlap of the cuneiform was presented. Weightbearing x-rays did not provide additional information. The anatomical location of the fracture was identified only after a computed tomography scan was performed. An incidental finding, bilateral bipartite medial cuneiforms, was also observed on the computed tomography scan, which contributed to the overlap on routine radiographs. The anatomy of the bipartite medial cuneiforms seen on computed tomography was similar to that described by Barlow in 1942. Retrospective comparison to the initial radiographs with the computed tomography scan sections did reveal bipartite medial cuneiforms on these films as well. The podiatric physician should keep bipartition in mind when evaluating x-rays for any osseous pathology, especially fractures. PMID- 1403739 TI - A successful technique for the treatment of diabetic neurotrophic ulcers. AB - Over 90% of the diabetic neurotrophic ulcers treated with the felted foam technique at the Cleveland Foot Clinic have completely healed. The average healing time for plantar ulcers has been approximately 8 weeks. After the ulcerations have healed, molded shoes or orthopedic shoes with Plastazote inserts are prescribed. The felted foam technique is simple to perform in an office setting and can be used by both the novice and the experienced practitioner. PMID- 1403740 TI - Achilles peritendinitis. A literature review with case report. PMID- 1403741 TI - Medial skive technique. PMID- 1403742 TI - Crescentic osteotomy. PMID- 1403743 TI - Public health. PMID- 1403744 TI - Tricorrectional bunionectomy. PMID- 1403745 TI - Calculating the surgically induced refractive change following ocular surgery. AB - Calculating the surgically induced refractive change following ocular surgery is important for evaluating the results of keratore-fractive procedures, smaller incisions and various wound closures for cataract surgery, and the effect of suturing techniques and suture removal following corneal transplant surgery. We present a ten-step method of calculating the spherical- and cylindrical-induced refractive change in a manner suitable for a programmable calculator or personal computer. Several applications are given including (1) adding the overrefraction to the spectacle correction, (2) determining the surgically induced refractive change from the preoperative and postoperative refractions, (3) determining the surgically induced refractive change from the K-readings, (4) rotating axes, (5) determining the power at meridians oblique to the principal meridians of a spherocylinder, (6) determining the coupling ratio, and (7) averaging axes. Standard methods for calculating and reporting aggregate results are also given. PMID- 1403746 TI - Hydrodynamic analysis of intraocular pressure changes during anterior chamber procedures. AB - Variations in intraocular pressure (IOP), observed by us and other authors in closed-system anterior chamber procedures, are explained using a simple hydrodynamic analysis based on the Bernoulli equation. Calculations show that the sudden increases in IOP (pressure spikes) measured during anterior segment surgery are due primarily to the small size of the infusion cannulas and are exacerbated by high infusion rates. Accurate measurement of these IOP variations requires placement of the pressure sensors in situ and is not possible by remote pressure sensing at the infusion line or the console. This work indicates that closed-system procedures could benefit from accurate monitoring of intraoperative IOP and could use these measurements for automatic IOP control during surgery. PMID- 1403747 TI - Prospective experimental study of factors related to posterior chamber intraocular lens decentration. AB - The effect of posterior chamber intraocular lens (IOL) dimensions, design, style, loop fixation, and anterior capsular tears on decentration were investigated in an experimental model. Nine posterior chamber IOLs of various designs and styles with loop diameters between 12.0 and 14.0 mm and optic diameters between 5.0 and 7.0 mm were implanted in human eyes obtained post mortem. Symmetrical and asymmetrical fixation were investigated in eyes with and without radial tears using the Miyake posterior view technique. Location of IOL loops proved to be the most significant factor in IOL decentration. Decentration was least with symmetrical bag/bag fixation and no radial tears (mean = 0.20 +/- 0.05 mm). Asymmetrical bag/sulcus fixation in the presence of anterior capsular tears was associated with the highest decentration rate (mean 0.68 +/- 0.28 mm). Optic size and total loop diameter had no apparent effect on IOL centration in the immediate postoperative period. PMID- 1403748 TI - Drug interaction with intraocular lenses of different materials. AB - The uptake and washout kinetics of four drugs representing different classes of ophthalmic medications were measured in intraocular lenses of different materials. The materials ranged from hydrogel lenses to poly(methyl methacrylate) (PMMA), Acrysof (acrylic/methacrylic), and two types of silicone lenses (Chiroflex and AMO SI-18NB). Uptake was determined after seven days of immersion in a large volume of Ringer's solution containing drug concentrations that equaled those found in aqueous humor 30 minutes to one hour after topical administration. Washout was determined after placing lenses in 1 ml of 0.9% saline for 24 hours. Only hydrogel lenses could be digested in acid to measure lens uptake directly. The PMMA, Acrysof, and silicone lenses behaved similarly toward gentamicin and dexamethasone--low uptake (less than 3.5 ng/mg lens) and low washout (less than 4.0%). Their uptake of norepinephrine was lower (less than 0.7 ng/mg lens) but the washout varied from 29% (AMO silicone) to 100% (PMMA and Acrysof). The pilocarpine uptake was the lowest of drugs tested (less than 0.03 ng/mg lens) and the washout varied from 1.5% (acrylic) to 100% (PMMA and Chiroflex silicone). Hydrogel lenses took up the most drug in the following order: dexamethasone greater than pilocarpine greater than gentamicin greater than norepinephrine. Washout was high, ranging from 83% to 98%. Despite the greater uptake and washout, the maximum drug uptake would only provide one-tenth of the greatest aqueous humor concentration that occurs after topical drug administration. Intraocular lenses of the materials tested did not interfere with the intraocular drug pharmacokinetics, nor did the data indicate that presoaking intraocular lenses of these materials in drugs would enhance post-surgical intraocular drug concentrations. PMID- 1403749 TI - Practice styles and preferences of ASCRS members--1991 survey. American Society of Cataract and Refractive Surgery. AB - A survey of the practice styles and preferences of 1991 ASCRS members with a U.S. zip code was performed in August 1991. Approximately 3,935 questionnaires were sent and approximately 40% (1,574) were returned after two months. Three main profile questions were used to cross-analyze the results: the age of the ophthalmologist, the volume of cataract surgery per month, and the geographic location. This report also compared the data with previously published surveys of the ASCRS and the Academy memberships. PMID- 1403750 TI - Changing trends in explanted intraocular lenses: a single center study. AB - Over a nine-year period, our practice removed 1,091 intraocular lenses. The most common type of lens requiring explantation was the closed-loop anterior chamber lens (58.6%). The Stableflex lens represented the largest percentage of all removed lens types (28.8%). The number of closed-loop anterior chamber lenses requiring removal peaked in 1988 and then gradually declined. All other lens styles have shown gradually increasing removal rates. Older style iris-fixated lenses and rigid anterior chamber lenses, which have not been implanted for several years, have increasing removal rates. Late breakage of fixational polypropylene sutures with pupil-supported iris-fixated lenses have occurred in five cases; the average time from implantation to suture breakage was 112 months. PMID- 1403751 TI - Explantation of posterior chamber lenses. AB - A consecutive series of 119 explanted posterior chamber lenses is reviewed. Seventy (58.8%) were removed because of dislocation or improper fixation, 15 (12.6%) because of anisometropia, and 18 (15.1%) because of chronic inflammation. Sixty-two (52.1%) of these explantations probably occurred for reasons that can be avoided by changes in preoperative, operative, or postoperative techniques. The rate of posterior chamber lens explantations is quite low considering the large number of lenses implanted; with changing surgical techniques, we anticipate that the number of lenses requiring removal will decrease. PMID- 1403752 TI - Intraocular lens implantation in microphthalmic patients. AB - Microphthalmos is a developmental disorder of the eye consisting of a smaller than normal eye. This disorder can present as an isolated condition or associated with other systemic alterations. It is not uncommon for patients with microphthalmos to have congenital cataracts along with other ocular and systemic abnormalities. This paper reports the experience with 11 microphthalmic eyes of seven patients who had primary or secondary intraocular lens (IOL) implantation over a six-year period from 1985 to 1991. In all cases the IOL had a 13.5 mm or 14.0 mm overall diameter and a 6.0 mm or 6.5 mm optic. It was difficult to obtain documentation of objective visual improvement in many of these cases because of the associated nystagmus. However, all patients reported subjective improvements. These results suggest that with proper technique and lens selection microphthalmic patients should be considered for IOL implantation with relative safety and success. PMID- 1403753 TI - Long-term study of children with implanted intraocular lenses. AB - We studied children between five and 15 years of age who were implanted with intraocular lenses (IOLs). The subjects comprised eight cases of traumatic cataract, 11 of congenital cataract, and six of steroid cataract. The follow-up ranged from four months to nine and one half years. Twenty of the eyes studied achieved a postoperative visual acuity of equal to or better than 20/40. Binocular function was retained in most cases. Postoperative complications included seven cases of posterior iris synechia, three of iris capture, one of transitory elevated intraocular pressure, and one of cystoid macular edema. Corneal endothelial studies were normal in the eyes in which posterior chamber IOLs were implanted. PMID- 1403754 TI - Study of acute intraoperative suprachoroidal hemorrhage. AB - Acute intraoperative suprachoroidal hemorrhage or effusion (AISH) was studied in a prospective manner over the past three years. In a general cataract surgery population of 2,523 patient eyes, 15 (0.6%) experienced an AISH. Results of a specific surgical management technique are presented. Surgical control of the AISH consisted of immediate closure of the incision and application of pressure directly to the eye. This tamponades the effusion or hemorrhage, which allows coagulation and completion of the case. There was no attempt to drain the suprachoroidal space. All cases were completed the same day, usually within an hour. The postoperative visual acuities were quite good--20/40 or better in 93% of cases. Factors contributing to AISH were 4+ brunescent nuclear sclerosis, the large incision used with nucleus expression extracapsular cataract extraction, and the combination of anticoagulation and systemic vascular disease. PMID- 1403755 TI - Effect of a superficial and a deep scleral pocket incision on the incidence of hyphema. AB - Deep tunnel scleral pocket incisions were developed to control surgically induced astigmatism following cataract and intraocular lens implantation surgery. A more superficial, shallow scleral pocket incision was developed to reduce the rate of postoperative hyphema. To test its effectiveness, a randomized prospective clinical study was performed. One hundred twenty-nine eyes of 129 patients were randomized: 66 to receive a deep tunnel pocket and 63 to receive the superficial pocket. In both groups the incision was made 3 mm posterior to the limbus. For the deep pocket cases, a blade setting of 0.27 mm was used and the wound was dissected forward toward the entry site, creating a long, deep, narrow tunnel. For the superficial wound cases, a 0.17 mm blade setting was used and the entire wound was dissected to the edge of the anatomic limbus, creating a thin scleral flap. The left side was then fanned out toward the left with the entry site slightly into clear cornea. At one day after surgery, 22 cases (34%) in the deep pocket group and four cases (6%) in the superficial pocket group had hyphemas. The difference in hyphema rates was statistically significant (P less than .001). PMID- 1403756 TI - Intraocular pressure following small-incision cataract surgery and polyHEMA posterior chamber lens implantation. A comparison between acetylcholine and carbachol. AB - Ninety patients who had phacoemulsification and implantation of a flexible polyHEMA intraocular lens (IOGEL 1103) were assigned to three groups. After evacuation of sodium hyaluronate retrolentally from the capsular bag, 0.5 ml of 1% acetylcholine chloride, 0.01% carbachol, or balanced salt solution was instilled into the anterior chamber following wound closure. Intraocular pressure (IOP) was measured the day before, and six hours, 18 hours, and one week postoperatively. No topical or systemic antiglaucomatous drug was given during the study period. Preoperatively and one week postoperatively there was no significant difference between the three groups (P greater than .01). At six hours postoperatively the mean IOP decreased in the carbachol group (-2.8 mm Hg) and increased in the acetylcholine and control groups (+0.6 mm Hg and +/- 4.7 mm Hg) when compared with baseline pressures. At 18 hours the mean change from baseline was -3.0 mm Hg in the carbachol group, +0.8 mm Hg in the acetylcholine group, and +2.3 mm Hg in the control group. At six hours IOP exceeding 22 mm Hg was observed in ten of the control patients (30%) receiving balanced salt solution intracamerally and four of the acetylcholine patients (13.3%) but none of the carbachol patients. At 18 hours IOP remained above 22 mm Hg in three of the acetylcholine patients (10%) and four of the control patients (13.3%). Only one of the carbachol patients developed an increase of IOP up to 26 mm Hg at 18 hours. Removal of viscoelastic substances from behind the IOL reduced the incidence of pressure spikes in the early postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403757 TI - Relationship between postoperative pupil size and disability glare. AB - A group of 40 postoperative cataract patients had Miller-Nadler glare testing performed before and after midpupillary pharmacologic dilation. The results indicated that pupillary enlargement is associated with increased glare disability. For that reason it is essential to maintain normal pupil shape and function after cataract surgery, a difficult task in cases with miotic pupils. PMID- 1403758 TI - Cortical cleaving hydrodissection. AB - In this technique, I/A of cortex as a separate step can be omitted, thereby eliminating that portion of the surgical procedure in which posterior capsular disruption most frequently occurs. Residual cortical cleanup is accomplished in the presence of a posterior chamber IOL which protects the poserior capsule by holding it remote from the aspiration port. PMID- 1403759 TI - Divide and conquer phacoemulsification. One-handed variant. AB - A one-handed variation of Gimbel's "divide and conquer" phacoemulsification technique is described. Instead of bimanual cracking, the lens sections are cut, rotated, cut, and removed in sequence. PMID- 1403760 TI - Preplaced inferior iris suture method for small pupil phacoemulsification. AB - A surgical method for managing poorly dilating pupils preoperatively is presented. A fine polypropylene suture is preplaced through the inferior iris sphincter prior to an inferior radial iridotomy in preparation for nucleus fracture endolenticular phacoemulsification. Placing the suture prior to the iridotomy assures proper aesthetic and functional alignment of the incised iris pillars, while enlarging the pupil inferiorly accommodates in-the-bag nucleus emulsification. This new surgical method maintains pupillary appearance and function postoperatively. PMID- 1403761 TI - Small pupil enlargement during cataract extraction. A new method. AB - A new method for enlarging a small pupil during cataract extraction is described. The technique is simple and safe, and uses new instruments that reduce or entirely eliminate the need to incise or suture the iris. This method of pupil enlargement can be used for extracapsular cataract extraction and phacoemulsification procedures. PMID- 1403762 TI - Posterior chamber intraocular lens implantation in a patient with oculocutaneous albinism. AB - A 56-year-old woman with tyrosinase-negative oculocutaneous albinism complained of gradually decreasing vision in the left eye. Her visual acuity was 20/300 in the right eye and hand motion in the left eye. She had pink skin and white hair and cilia. On examination, bilateral hypopigmented irides, an opaque lens in the left eye, a hypopigmented fundus in the right eye, and nystagmus were found. An extra-capsular cataract extraction with posterior chamber intraocular lens (IOL) implantation was performed. After retrobulbar anesthesia was administered, the nystagmus ceased temporarily. Postoperatively, visual acuity in the left eye improved to 20/200. We believe IOL implantation is useful in the treatment of cataracts in albino patients. PMID- 1403763 TI - Spontaneous extrusion of an intraocular lens implant. AB - A 51-year-old man with ankylosing spondylitis had intracapsular cataract extraction and anterior chamber lens implantation in the left eye in 1985. He had localized sclerokeratitis around the corneal section and a protracted anterior uveitis in the immediate postoperative period. He developed a spontaneous extrusion of the implant in 1991 (six years later). The extrusion was through a site 1.5 mm posterior to the previous surgical section. There was no corneal decompensation or corneal melt and no history of trauma. Signs of localized scleritis were present. It is suggested that anterior chamber lens implantation should be avoided under these circumstances. PMID- 1403764 TI - Consultation section. Attitudes regarding the concomitant use of anti-coagulants with elective cataract surgery. PMID- 1403765 TI - Capsular bag distension. PMID- 1403766 TI - Anterior capsular opacification: is aqueous the culprit? PMID- 1403767 TI - Pulmonary embolus in pregnancy. PMID- 1403768 TI - Understanding tuberculosis: implications for pregnancy. PMID- 1403769 TI - Challenging diagnosis: management of the obstetric patient with adult respiratory distress syndrome. PMID- 1403770 TI - Asthma and pregnancy: opportunities for enhancing outcomes. PMID- 1403771 TI - Alterations of the respiratory system in the neonate: implications for clinical practice. PMID- 1403772 TI - Exogenous surfactant therapy for premature infants. PMID- 1403773 TI - Does routine nursing care complicate the physiologic status of the premature neonate with respiratory distress syndrome? PMID- 1403774 TI - Transition to home: discharge planning for the oxygen-dependent infant with bronchopulmonary dysplasia. PMID- 1403775 TI - Dose-dependent toxicokinetics of L-689,502, a potent human immunodeficiency virus protease inhibitor, in rats and dogs. AB - L-689,502, N-[2(R)-hydroxy-1(S)-indanyl]-5(S)-(1,1-dimethylethoxy- carbonylamino) 4(S)-hydroxy-6-phenyl-2(R)-(4-[2-(4- morpholinyl)ethoxy]phenyl)methyl hexanamide, is a potent inhibitor of human immunodeficiency virus-1 protease. The effect of dose on the elimination kinetics of L-689,502 was studied in rats and dogs. After i.v. administration, total plasma clearance of L-689,502 in rats decreased with increasing dose; the clearance decreased from 181 ml/min/kg at 1 mg/kg to 86 ml/min/kg at 20 mg/kg. Similar results were observed in dogs; clearance fell from 29 ml/min/kg at 0.5 mg/kg to 17 ml/min/kg at 10 mg/kg. Bile flow in rats was retarded in a dose-dependent manner after a single i.v. injection of L-689,502. The cholestatic effect was reversible and maximal at 5 mg/kg i.v. Consistent with the cholestatic effect, L-689,502 caused an increase in serum levels of aminotransferase. After i.v. administration of L-689,502 (10 mg/kg), alanine aminotransferase increased from 50 to 370 IU/liter and aspartate aminotransferase from 120 to 700 IU/liter. Moreover, pretreatment of rats with L-689,502 resulted in a significant decrease in the elimination kinetics of antipyrine and diflunisal, as well as of L-689,502 itself. Collectively, these results suggest that the dose-dependent kinetics of L-689,502 in rats and dogs are more likely due to hepatotoxicity caused by the drug than to capacity-limited metabolism. PMID- 1403776 TI - A comparison of the potency of selective L-calcium channel blockers in human coronary and internal mammary arteries exposed to serotonin. AB - The actions of L-type calcium channel blockers on the contractile response to serotonin and to K(+)-depolarization have been studied in human coronary artery and in human internal mammary artery. The effect of ketanserin indicated that in both arteries serotonin action may be related not only to 5-serotonin2 but also to other serotonin receptors. In fura-2-loaded coronary and mammary arteries, exposed to serotonin (10 microM), nisoldipine (1 microM) and verapamil (10 microM) reversed completely the increase in [Ca++] cyt but not the contraction. The Ca++ antagonist-resistant contraction was equal to 26.2 +/- 2.1% of controls (n = 57) in coronary artery and to 51.7 +/- 4.2% (n = 19) in internal mammary artery. The concentration inhibiting by 50% the tonic contraction to serotonin sensitive to calcium channels blockade was 61-fold lower in human coronary artery than in human internal mammary artery with nisoldipine, but only 3.7-fold lower with nifedipine. There was no significant difference with diltiazem and verapamil. When human coronary artery and human internal mammary artery were exposed to a 100-mM KCl depolarizing solution, their sensitivity to nisoldipine was not significantly different. Preincubation with calcium antagonists in a 40 mM KCl solution reversibly increased the inhibitory effect of nisoldipine but not that of the other calcium antagonists. Comparison of radioligand and functional data shows that inhibition by calcium antagonists of the response to both serotonin and K(+)-depolarizing solution may be related to interaction with L type calcium channels. The results indicate that the very high sensitivity to nisoldipine of the tonic response evoked by serotonin in human coronary artery might be related to the voltage-dependence of this dihydropyridine. PMID- 1403777 TI - Serotonin-induced relaxation in canine coronary artery smooth muscle. AB - Serotonin (5-HT) is a potent contractile agonist in canine coronary artery devoid of endothelium; however, in higher concentrations 5-HT produces concentration dependent relaxation by activating an as yet uncharacterized receptor. This study explored the possibility that 5-HT-induced relaxation was mediated by interaction with a member of the 5-HT1, 5-HT2, 5-HT3, or 5-HT4 receptor family. 5-HT, 5 carboxamidotryptamine and 5-methoxytryptamine produced concentration-dependent relaxation in vitro in tissues precontracted with prostaglandin F2 alpha (10 microM). The agonist rank order potency for relaxation was 5 carboxamidotryptamine > 5-HT > 5-MeOT. 8-hydroxydipropylaminotetralin (8-OH DPAT), dipropyl-5-CT, 5-methyltryptamine, sumatriptan, alpha-methyl-5-HT and 2 methyl-5-HT did not produce significant relaxation. The 5-HT1/beta adrenergic receptor antagonist propranolol (1 microM) did not antagonize 5-HT-induced relaxation. 5-HT-induced relaxation was not blocked by tetrodotoxin (0.3 microM), suggesting that neuronal depolarization to release mediators from nerves was not responsible for the relaxation. Neither ketanserin (1 microM) nor ritanserin (1 microM) antagonized 5-HT-induced relaxation, suggesting that 5-HT2 and 5-HT1C receptors do not mediate relaxation. ICS 205-930 (10 microM), a 5-HT3/5-HT4 receptor antagonist, shifted the 5-HT concentration-response curve modestly to the right (pKB = 5.1 +/- 0.1). Cisapride, a 5-HT4 receptor agonist, was not effective either as an agonist (up to 10 microM), or as an antagonist (1 microM) of 5-HT-induced relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403778 TI - Pulmonary accumulation of propranolol in vivo: sites and physiochemical mechanism. AB - Despite the therapeutic importance of propranolol and the potential usefulness of propranolol extraction measurements for the assessment of lung disorders, the pulmonary disposition of propranolol remains poorly understood. The extraction, accumulation and distribution of propranolol in lungs of conscious and anesthetized sheep were investigated by indicator-dilution methods, lung lymph fistula preparations and bronchoalveolar lavage. Pulmonary extraction of propranolol from plasma (0.81 +/- 0.03) was significantly less than that of imipramine (0.89 +/- 0.03), not significantly different from that of lidocaine (0.74 +/- 0.03) and much greater than that of water (0.44 +/- 0.02), whereas there were no differences in apparent red blood cell extraction of each indicator from plasma in vitro as determined under similar conditions (0.08-0.1). Pulmonary accumulation of imipramine (78 +/- 3%), lidocaine (52 +/- 4%), propranolol (37 +/ 4%) and water (7 +/- 2%), after a single pass through the pulmonary circulation, correlated positively with octanol/saline partition coefficients but not with pKa values. After bolus i.v. injection of [3H]propranolol, tritium concentrations in lung lymph increased rapidly to exceed plasma concentrations within 60 min and tritium concentrations in bronchoalveolar lavage equaled plasma concentrations 5 to 15 min after injection. It is concluded that by a mechanism not involving molecular charge, propranolol permeates capillary endothelium and alveolar epithelium to accumulate in hydrophobic regions of the lungs. This study in normal sheep suggests that reduced propranolol extraction by damaged lungs reflects pathological alterations other than endothelial cell dysfunction, such as pulmonary edema. PMID- 1403779 TI - Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. AB - Subcutaneous injection of formalin into the dorsal surface of the hindpaw evoked a two-phased flinching (phase 1:0-9 min; phase 2: 10-60 min) of the injected paw. Intrathecal administration of the nonsteroidal anti-inflammatory drugs (NSAID) produced minimal effects upon phase 1, but showed a significant, though submaximal, dose-dependent suppression of the phase 2 response. Ordering of i.t. potency was (ID50 in nmol): indomethacin (1.9) > or = flurbiprofen (2.1) > ketorolac (5.2) > or = zomepirac (5.9) > S(+)ibuprofen (16) > or = ibuprofen(racemic) (19) > acetylsalicylic acid (27) > acetaminophen (250) > R( )ibuprofen (> 270) = 0. Intraperitoneal administration also produced a dose dependent inhibition of phase 2, but only at doses which were 100 to 1000 times higher than those required to produce similar effects after i.t. injection. Intrathecal and i.p. dose-response curves showed similar distinct plateaus of maximum achievable inhibition (intrinsic activity) of the phase 2 behavior, ranging from 20 to 50% of the control response. Varying the time of drug injection reveals that injection 9 min after formalin yielded effects the same as those observed when the agent was given 2 min before formalin. Pretreatment at longer intervals indicated that the duration of the antinociceptive effect was between 3 to 6 hr after the i.t. injection. The i.t. injection of the highest doses of the several NSAID were without significant effect upon the 52.5 degrees C hot plate test. These studies indicate that NSAID have a powerful effect upon spinal nociceptive processing evoked by the s.c. injection of formalin. PMID- 1403780 TI - Membrane potential in myenteric neurons associated with tolerance and dependence to morphine. AB - Chronic treatment of guinea pigs with morphine produces subsensitivity (tolerance) of the longitudinal smooth muscle-myenteric plexus preparation to a variety of inhibitory agonists (e.g., mu opioid, alpha adrenoceptor and adenosine receptor agonists) and supersensitivity (dependence) to a variety of excitatory agonists (e.g., nicotine, 5-hydroxytryptamine and potassium ions). The present investigation was to determine if these changes in sensitivity could be related to changes in electrical properties of the S and AH neurons in the myenteric plexus. S neurons from morphine-implanted animals were significantly depolarized (7 mV) relative to those from placebo-implanted animals, whereas the membrane potential of AH neurons was unchanged. Approximately 60% of S neurons were hyperpolarized by morphine. In this subset of neurons, membranes were significantly depolarized but the threshold was unchanged in morphine-implanted animals. This means that resting potentials of S neurons from tolerant preparations are closer to threshold. The hyperpolarization produced by morphine (0.1 microM) was similar in preparations from morphine- and placebo-implanted animals. Thus, the partially depolarized state of S neurons in the myenteric plexus is the cause of the subsensitivity and supersensitivity to agonists and can explain both tolerance and dependence. Changes in opioid receptors or their coupling to potassium channels do not appear to contribute to tolerance in the longitudinal smooth muscle-myenteric plexus. PMID- 1403781 TI - Aldose reductase and myo-inositol in endothelial cell dysfunction caused by elevated glucose. AB - A possible relationship between aldose reductase activity and myo-inositol levels and endothelium-dependent relaxations was examined in isolated rabbit aorta incubated with elevated concentrations of glucose (44 mM) for 6 hr to mimic hyperglycemic conditions. Rings of aorta incubated in elevated glucose and contracted submaximally by phenylephrine showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with aorta incubated in control (5.5 or 11 mM) glucose. Acetylcholine-induced relaxations of aorta incubated in hyperosmotic mannitol (44 mM) were not different from those incubated in control glucose. Treatment with two structurally unrelated aldose reductase inhibitors, sorbinil or zopolrestat, or supplementation with myo inositol, prevented the abnormal acetylcholine relaxations of aortic rings caused by elevated glucose. No effects of sorbinil, zopolrestat or myo-inositol were observed on the response to acetylcholine of aorta incubated in control glucose. Neither sorbinil nor myo-inositol affected the increase in release of vasoconstrictor prostanoids caused by elevated glucose. These findings suggest that sorbitol accumulation and myo-inositol depletion contribute to the abnormal endothelial cell function caused by exposure to elevated glucose. The increased release of vasoactive prostanoids is either independent of, or possibly contributes to, the abnormal aldose reductase activity and/or myo-inositol depletion in intact blood vessels exposed to elevated concentrations of glucose. PMID- 1403782 TI - Cardiac effects of 3,5-diiodothyropropionic acid, a thyroid hormone analog with inotropic selectivity. AB - Thyroid hormone exerts a strong positive inotropic action on the heart and induces alpha-myosin heavy chain (MHC) gene expression. 3,5-Diiodothyropropionic acid (DITPA), a carboxylic acid analog with low metabolic activity, was observed to induce alpha-MHC mRNA in heart cell culture with EC50 approximately 5 x 10(-7) M. To determine if the compound has positive inotropic actions, the effects of DITPA and L-thyroxine on heart rate, left ventricular pressures, left ventricular dP/dt, myosin isoenzymes and hepatic alpha-glycerolphosphate dehydrogenase activity were compared in hypothyroid rats. Binding affinities of DITPA and triiodothyronine for bacterially expressed alpha-1 and beta-1 thyroid hormone receptors (TRs) also were determined. Over the dosage range of 150 to 1500 micrograms/100 g, DITPA produced increases in left ventricular dP/dt comparable to those obtained with L-thyroxine at dosages of 1.5 to 15 micrograms/100 g, but with significantly less tachycardia. The increase in alpha-MHC mRNA was about the same with both compounds whereas alpha-MHC protein content and GPDH activity increased less with DITPA. These differences could not be explained by preferential binding of DITPA to TR subtypes. Because heart rate is a major determinant of myocardial oxygen consumption, DITPA is able to achieve increased cardiac performance at lower myocardial oxygen costs. PMID- 1403783 TI - The effect of the atypical antipsychotic drug, amperozide, on carrier-mediated striatal dopamine release measured in vivo. AB - The effect of the novel atypical antipsychotic drug, amperozide, on carrier mediated dopamine efflux was studied using in vivo microdialysis in the striatum of awake-behaving rats. Amperozide was infused directly through the dialysis probe. This local infusion produced a concentration-dependent increase in striatal dopamine overflow. This increase was attenuated when a Ca(++)-free perfusion medium was used. Local infusion of amperozide blocked dopamine efflux after the systemic administration of amphetamine in a concentration-dependent manner. The antagonistic effect of amperozide (50 microM) on amphetamine-induced efflux of dopamine was not attenuated under Ca(++)-free conditions. Similar to its effects on amphetamine-induced dopamine efflux, amperozide (50 microM) attenuated the increase in dopamine overflow produced by ouabain (10 microM) but not veratridine (15 microM). The systemic coadministration of amperozide (10 mg/kg, i.p.) and haloperidol (2 mg/kg, i.p.) increased extracellular dopamine levels in an additive manner when compared to the increases observed after the administration of either drug alone. Overall, these data indicate that amperozide acts on the dopamine transporter to inhibit carrier-mediated release. PMID- 1403784 TI - Tamoxifen-resistant human breast cancer cell growth: inhibition by thioridazine, pimozide and the calmodulin antagonist, W-13. AB - Estrogen receptor (ER)-negative human breast cancer cell lines (MDA-MB-231 and MDA-MB-435) and ER-positive derivatives of the MCF-7 cell line selected for growth in the presence of antiestrogens (LY2 and RR) were used as in vitro models of tamoxifen-resistant human breast cancer in this study. The sensitivity of the tamoxifen-sensitive (MCF-7) and tamoxifen-resistant human breast cancer cell growth to two noncytotoxic neuroleptic drugs, pimozide and thioridazine, and the anticalmodulin agent, W-13, were compared. Inhibition of cell growth was measured as a decrease in cell number following a 72-h incubation with drug. Growth of the ER-negative cell lines MDA-MB-231 and MDA-MB-435 was inhibited by all three drugs. The average Ki values in these two lines were 6.3 and 3.8 microM for pimozide and 4.1 and 15 microM for thioridazine, respectively. Both ER-negative cell lines were more sensitive than MCF-7 cells to growth inhibition by W-13. MCF 7 cells selected for antiestrogen resistance were sensitive to growth inhibition by W-13 and thioridazine (LY2, average Ki = 10.4 microM; RR, average Ki = 5.2 microM). LY2 and RR cells were resistant to pimozide except when treated with estradiol (Ki = 4.6 and 7.9 microM, respectively). Pimozide, thioridazine and W 13 all exerted different effects on the distribution of human breast cancer cells within the cell cycle, suggesting that each drug may utilize a distinct pathway for inhibition of cell growth. We conclude that all three drugs are potential noncytotoxic alternatives to tamoxifen for the treatment of tamoxifen-resistant human breast cancer. PMID- 1403785 TI - Block of voltage-gated potassium currents by anticonvulsant U-54494A in mouse neuroblastoma cells. AB - U-54494A [(+-)-cis-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)-cyclohexyl] benzamide], an anticonvulsant and Na channel blocker, was examined for its interaction with delayed rectifier K channels in mouse neuroblastoma cells (NIE 115) using whole-cell and inside-out configurations of the patch clamp techniques. U-54494A at anticonvulsant doses reversibly blocked the tetraethylammonium-sensitive outward K current in a time-dependent manner without affecting the current-voltage relationship. Analysis of the time-dependent block suggests interaction of U-54494A with the open state, but not with the resting state of the K channel. Furthermore, the drug showed no interaction with inactivated states of the K channel because it produced no noticeable effect on the steady-state inactivation curve or the recovery of the channel activity from inactivated states. The drug shifted the steady-state activation curve to a hyperpolarizing direction. This shift seems to result from underestimations of the maximal conductance of the K channel in the presence of U-54494A, because of its progressively increasing potency to block the K currents as the membrane potential became more depolarized. The potency of the drug was enhanced not only by depolarized membrane potentials, but also by raising the external pH. These results suggest that U-54494A interacts with a channel binding site which is located within the membrane electric field and approachable from the cytoplasmic side. The proposal was supported further by single channel recordings with inside out patches in which U-54494A induced flickery blocks of single channel openings of the delayed rectifier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403786 TI - Selective inhibitory effects of calcium channel antagonists on the two components of the neurogenic response of guinea pig vas deferens. AB - The effects of L-type calcium channel antagonists and omega-conotoxin on the contractile responses of guinea pig vas deferens were examined in vitro. Electrical stimulation of the postganglionic hypogastric nerve induced biphasic contraction consisting of rapid phasic and delayed tonic components. L-type calcium channel antagonists, such as diltiazem, verapamil and nicardipine, mainly inhibited the delayed tonic component, whereas omega-conotoxin mainly inhibited the rapid phasic component. Stimulations in the presence of prazosin and alpha, beta-methylene ATP induced rapid transient and delayed contraction, respectively, which were inhibited by omega-conotoxin and L-type calcium channel antagonists, respectively. Short-term stimulation with five pulses induced a small fast phasic contraction. This contraction, which could be desensitized by alpha, beta methylene ATP, was inhibited by omega-conotoxin, but not by L-type calcium channel antagonists. At the concentrations used in the present study, none of the calcium channel antagonists inhibited the contractions induced by exogenously added ATP or norepinephrine. These findings suggest that L-type calcium channel antagonists and omega-conotoxin inhibit the neurotransmissions mediated by norepinephrine and ATP, respectively, from the postganglionic nerve to the vas deferens of the guinea pig. Inhibition of the voltage-dependent calcium channel is discussed in relation to the mechanism of cotransmission in this preparation. PMID- 1403787 TI - Prejunctional muscarinic receptors in the deep muscular plexus of canine ileum: comparison with smooth muscle receptors. AB - Prejunctional muscarinic receptors from the deep muscular plexus of canine ileum were studied, and their properties were compared with those of the postjunctional receptors of the circular smooth muscle. In the purified synaptosomal fraction (a fraction containing primarily the axonal varicosities of deep muscular plexus), the muscarinic ligand N-[3H]methylscopolamine labeled an apparently homogenous population of receptors (nH = 1) with a Kd of 2.7 nM and a Bmax of 195 +/- 44 fmol/mg protein (mean +/- S.D., n = 4). These receptors showed a high affinity for the M3/M1-selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (pKi = 7.41); in contrast, the pKi values of pirenzepine (5.60), methoctramine (5.65) and AF-DX 116 (5.21) implied little selectivity for these subtypes. The binding properties of muscarinic receptors in the synaptosomal fraction were different from the binding properties of muscarinic receptors in the purified circular smooth muscle plasma membranes. Most notably, the circular smooth muscle receptors had significantly lower affinity for N [3H]methylscopolamine (Kd = 16 nM) with a Bmax value of 2088 +/- 276 fmol/mg. The affinities of the M2 subtype-selective muscarinic antagonists methoctramine and AF-DX 116 were similar in both membrane preparations. The receptor population associated with the deep muscular plexus synaptosomal fraction was linked to the inhibition of adenylate cyclase activity, as demonstrated by a concentration dependent, atropine-sensitive inhibition of the forskolin-stimulated enzyme in the presence of muscarinic agonists carbachol and oxotremorine. Based on the pharmacological observations presented here, the prejunctional muscarinic receptors in the axonal varicosities of deep muscular plexus are different from the postjunctional receptors present in the circular smooth muscle. PMID- 1403788 TI - Lipid solubility of sedative-hypnotic drugs influences hypothermic and hypnotic responses of long-sleep and short-sleep mice. AB - The anesthetic potency of many agents, including alcohols, barbiturates and other sedative-hypnotic drugs, is influenced by lipid solubility. Previous studies from our laboratory, however, have demonstrated that genetic factors influence this relationship. We have reported that mouse lines selectively bred for differences in duration of ethanol-induced anesthesia, the long-sleep (LS) and short-sleep (SS) mice, differ in sleep-time response to water-soluble, but not lipid-soluble, sedative-hypnotic drugs. The studies described here sought to determine whether this same relationship exists for the hypothermic response produced by 17 sedative-hypnotic drugs in the LS and SS mice. Dose-response and time course relationships for hypothermic actions were determined and were compared with the dose-related anesthetic effects of the drugs. Hypothermic potencies increased along with lipid solubility for both the LS and SS mouse lines, but the rate of change differed for the two mouse lines. LS mice were more responsive to ethanol and other water-soluble drugs whereas the SS were more responsive to lipid soluble drugs; significant correlations were obtained between lipid solubility (log P-octanol-water partition coefficient) and relative LS-SS responsiveness to both the hypothermic and hypnotic actions of the 17 test drugs. Thus, both hypnotic and hypothermic actions of sedative-hypnotic drugs are correlated with lipid solubility. Possible explanation for these correlations include greater LS central nervous system sensitivity to water-soluble drugs and LS-SS differences in distribution of lipid-soluble drugs. PMID- 1403789 TI - A mechanistic study on enhancement of rectal permeability to insulin in the albino rabbit. AB - This study was conducted mainly to investigate the relative contributions of various mechanisms by which bile salts and EDTA may improve the in vitro rectal penetration of insulin in the albino rabbit. Insulin could not cross the rectal mucosa unless Na glycocholate or other penetration enhancers were present. Penetration enhancement was attributed primarily to Na glycocholate's ability to reduce the barrier function of the rectal membrane and to increase the fraction of insulin in its monomeric form, and secondarily to Na glycocholate's ability to protect insulin from proteolysis. Na glycocholate was more effective than Na taurocholate, but less effective than Na deoxycholate and polyoxyethylene-9 lauryl ether in enhancing rectal insulin penetration. Although EDTA at 0.01 and 0.1% did not affect rectal insulin penetration, it augmented the penetration enhancement effect of 1% Na glycocholate without causing additional damage to the rectal membrane, as judged by protein release. Such an action was attributed to the synergistic effect associated with: 1) an increase in the permeability of the paracellular pathway by EDTA and 2) an increase in the proportion of insulin in the monomeric form by Na glycocholate. Results from parallel in vivo experiments have indicated that it may be possible to achieve significant penetration enhancement by using a combination of otherwise membrane-damaging penetration enhancers which act by complementary mechanisms at concentrations that are both effective and well tolerated by mucosal epithelial cells. PMID- 1403790 TI - The discriminative stimulus effects of clozapine in pigeons: involvement of 5 hydroxytryptamine1C and 5-hydroxytryptamine2 receptors. AB - Pigeons were trained to discriminate i.m. injections of the atypical antipsychotic clozapine (1.0 mg/kg) from saline in a two-key operant procedure. In substitution tests, compounds that shared antagonistic action at 5 hydroxytryptamine (5-HT)1C and 5-HT2 receptors produced discriminative stimulus effects similar to clozapine: cyproheptadine, metergoline, mianserin, pizotifen and fluperlapine. 5-HT antagonists selective for 5-HT2 vs. 5-HT1C receptors (e.g., ketanserin, pirenperone, risperidone and methiothepin) failed to produce substantial clozapine-appropriate responding. Other serotonergic compounds failed to produce substantial clozapine-appropriate responding: the 5-HT3 antagonist, ondansetron; the 5-HT1A agonists, (+-)-8-hydroxy-2-(di-n-propylamino)tetralin and BMY 14802; the 5-HT1A/1B agonist, RU24969; the 5-HT1A partial agonist, NAN190; the 5-HT1C/2 antagonist, mesulergine; the 5-HT1 agonist, I-5-hydroxytryptophane; and the 5-HT1C/2 agonist, quipazine. Other reference compounds such as the typical antipsychotics, chlorpromazine and thioridazine; the selective dopamine D 2 antagonists, droperidol and sulpiride; the dopamine D-1 antagonist, SCH 23390; the antimuscarinics, atropine and scopolamine; the antihistamines, pyrilamine and diphenhydramine; the alpha-1 antagonist, prazosin; and the antidepressants, imipramine and chloromipramine also failed to produce clozapine-appropriate responding. Promethazine, cinanserin and amitriptyline produced only partial generalization to the clozapine cue. The results suggest that blockade of both 5 HT2 and/or 5-HT1C receptors is important in the pharmacological mediation of the discriminative stimulus effects of clozapine. Blockade of 5-HT2 receptors appears not to be sufficient to produce clozapine-like discriminative stimulus effects. The precise role of 5-HT1C receptors in the clozapine discriminative stimulus is unclear due to the lack of compounds selective for this receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403791 TI - Gentamicin-induced hypercalciuria in the rat: assessment of nephron site involved. AB - Two independent techniques were used in anesthetized rats in an attempt to locate the nephron site of the reduced tubular calcium reabsorption accompanying acute gentamicin infusion. The first technique was that of lithium clearance used to assess proximal sodium (and secondarily calcium) handling. Observations that lithium clearance was comparable in control and gentamicin-treated animals (1.83 +/- 0.39 vs. 1.46 +/- 0.14 ml.min-1 for first experimental period) suggests a lack of proximal effect of the drug. The second technique was that of tracer microinjection whereby superficial nephrons were injected with 45Ca and tubule calcium transport was assessed from the recovery of radioactivity in the final urine. 45Ca recovery values from distal microinjections were comparable in control and gentamicin-treated groups (81.1 +/- 2.0 vs. 77.7 +/- 4.6%). However, 45Ca recovery values from proximal microinjections were significantly higher in the gentamicin group (9.4 +/- 1.0 vs. 3.5 +/- 0.8%; P < .001). These data suggest that the effects of gentamicin on renal calcium handling are mediated at a nephron site proximal to the distal tubule (i.e., loop of Henle or proximal tubule itself). Closer examination of individual proximal micropuncture data may point to an effect occurring predominantly in the pars recta of the proximal tubule or loop of Henle. Taken together, the results of both parts of the present study suggest that the early physiological effects of gentamicin on the kidney occur in a different nephron segment from any subsequent nephrotoxicity. PMID- 1403792 TI - Lack of tolerance and physical dependence upon repeated treatment with the novel hypnotic zolpidem. AB - Zolpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors]. The present study investigated whether tolerance and physical dependence develop after repeated treatment with zolpidem as is observed with benzodiazepines. Mice were given zolpidem or the benzodiazepine midazolam (2 x 30 mg/kg, p.o.) for 10 consecutive days. Tolerance to central depressant effects (evaluated by recording spontaneous locomotor activity) and to anticonvulsant effects (measured against pentylenetetrazole-, electroshock- and isoniazid-induced convulsions) was assessed 42 hr after the last administration. A decrease in the latency to isoniazid-induced convulsions was taken as an index of physical dependence and was evaluated 3, 6, 14, 24, 42 and 67 hr after the end of chronic drug treatment. Repeated treatment with midazolam produced tolerance to its sedative and anticonvulsant activities as indicated by shifts of the dose-response curves by a factor of 3 to 5. Fourteen hr after discontinuation of treatment, spontaneous withdrawal was observed and lasted 3 days. When flumazenil was given 3 or 6 hr after the final midazolam injection, precipitated withdrawal was observed. In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects. Moreover, neither spontaneous nor flumazenil-induced precipitated withdrawal was observed in zolpidem-treated mice. PMID- 1403793 TI - Effects of intrauterine position on the hepatic microsomal polysubstrate monooxygenase and cytosolic glutathione S-transferase activity, plasma sex steroids and relative organ weights in adult male and female Long-Evans rats. AB - The intrauterine position of rat fetuses between siblings of the same or opposite sex has been reported to alter sexually dimorphic behavioral and reproductive traits in the adult. The intrauterine fetal position of adult rats is identified by a three letter code as mMm (a male, M, located between two male siblings, m-m) and fFf (a female, F, positioned between two females, f-f). This study sought to determine whether intrauterine location affected the hepatic polysubstrate monooxygenase and glutathione S-transferase activity, plasma sex steroid levels and organ weights in adult Long-Evans rats. The hepatic microsomal cytochrome P 450 content was higher in females located in utero between two male littermates (mFm) than in females positioned between two females (fFf). NADPH cytochrome c reductase activity was higher in mMm males (positioned in utero between two males) than in fMf males (males contiguous to two female littermates) and female rats. Hepatic microsomal testosterone 2 alpha- and 6 beta-hydroxylase activity was undetectable in fFf female but both activities were measurable in mFm female rats. Testosterone 7 alpha-hydroxylase and 5 alpha-reductase activity was higher in females than in males, and higher in fFf than in mFm females. Glutathione S transferase activity was not altered by fetal contiguity in male and female rats. Adult mMm males had a higher plasma testosterone level and relative gonadal weight, and lower plasma estradiol concentration than fMf males. The plasma progesterone concentration of fFf female was lower than that of mFm female rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403794 TI - In vitro and in vivo biotransformation and covalent binding of benzo(a)pyrene in Gunn and RHA rats with a genetic deficiency in bilirubin uridine diphosphate glucuronosyltransferase. AB - Like many polycyclic aromatic hydrocarbons in the environment, >30% of benzo(a)pyrene (BP), an environmental carcinogen and teratogen, is eliminated by glucuronidation, which competes with a toxifying pathway involving cytochrome P 450-catalyzed bioactivation of BP to a carcinogenic reactive intermediate, BP-7,8 diol-9,10-oxide. Genetic deficiencies in bilirubin UDP-glucuronosyltransferase (GT) occur in >5% of the population (Gilbert's disease, Crigler-Najjar syndromes), and this could predispose such people to the toxic effects of polycyclic aromatic hydrocarbons and other environmental chemicals that are eliminated substantially by glucuronidation. This hypothesis was evaluated in vitro and in vivo in homozygous Gunn and RHA rats, both of which are genetically deficient in GT. [7,10-14C]BP was incubated with rat liver microsomes, NADPH and uridine diphosphate-glucuronic acid. BP and its metabolites, including its glucuronide conjugates, were measured by high performance liquid chromatography with a radioisotope detector, and the covalent binding of BP to microsomal protein was measured by liquid scintillation counting. Compared with Wistar (Gunn) controls and RHA homozygous normal controls, microsomes from homozygous GT deficient Gunn and RHA rats demonstrated 18.5 to 48.5% lower production of the glucuronide conjugate, with 2 to 3-fold greater covalent binding of BP (P < .05). Elevated BP covalent binding correlated with reduced glucuronidation in both Gunn (r = -0.705, P = .003) and RHA rats (r = 0.824, P = .001). In vivo, the covalent binding of [G-3H]BP to hepatic DNA and microsomal protein was enhanced 2-fold and 1.5-fold, respectively, in homozygous RHA GT-deficient rats, compared with RHA GT normal controls (P < .05)(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403795 TI - Chronic cocaine treatment suppresses basal expression of zif268 in rat forebrain: in situ hybridization studies. AB - Transcription regulatory factors are rapidly induced in brain by a wide variety of stimuli and may be important in coordinating changes in gene expression underlying neuronal plasticity. In addition to the transient activation profile typically displayed by many of these genes, zif268 exhibits prominent basal expression in the brain that is dependent on synaptic activity. Accordingly, zif268 may play a key role in regulating neuronal gene expression induced by naturally occurring stimuli. Acute cocaine administration (15 mg/kg i.p.) produces a robust and transient induction of several transcription factors in the brain, including zif268. In the present study we report that, in contrast to the acute effects of a single dose, chronic cocaine treatment (15 mg/kg i.p., twice daily for a total of 10 injections), produces a widespread suppression of basal zif268 mRNA levels in rat forebrain between 8 and 24 hr after the last cocaine injection. This reduction is not evident after a single injection of cocaine or comparable chronic treatment with a structural analog, procaine, that does not share cocaine's uptake inhibitor properties. The suppression of basal zif268 expression may provide a mechanism for producing widespread effects of chronic cocaine administration on neuronal gene expression. PMID- 1403796 TI - Comparison of 5-hydroxytryptamine1A-mediated hyperpolarization in CA1 and CA3 hippocampal pyramidal cells. AB - 5-hydroxytryptamine (5-HT) hyperpolarizes hippocampal pyramidal cells in both areas CA1 and CA3 through an increase in potassium conductance. The receptor mediating the hyperpolarization in CA1 has been characterized as the 5-HT1A receptor, but has not been identified in area CA3. Intracellular recording techniques were used to record from CA1 and CA3 pyramidal cells in a hippocampal slice preparation. 5-HT agonists and antagonists were applied in known concentrations by bath perfusion. Antagonists were tested alone and for their ability to block the hyperpolarization elicited by 5-HT. The 5-HT1 agonist 5 carboxyamidotryptamine and 5-HT were full agonists and the 5-HT1A-selective ligand 8-hydroxydipropyl-aminotetralin hydrobromide was a partial agonist in both CA3 and CA1. The rank order potency was 5-carboxyamidotryptamine > 8 hydroxydipropyl-aminotetralin hydrobromide > 5-HT for both regions. The agonists were a half-log unit less potent and the maximum response elicited by 5 carboxyamidotryptamine and 5-HT was greater in area CA3 than in area CA1. The selective 5-HT1A antagonist BMY 7378 and the 5-HT1A/2 antagonist spiperone were competitive in area CA1, but insurmountable in area CA3. Other 5-HT antagonists that were not effective in blocking the 5-HT-mediated hyperpolarization included ketanserin, odansetron and BRL 24924. Based on these results, we conclude that the hyperpolarization elicited by 5-HT in areas CA1 and CA3 is mediated by the 5 HT1A receptor. However, there are significant differences in the nature of the 5 HT1A receptor-mediated hyperpolarization that may be attributed to differences in receptor-effector number, receptor-effector coupling and/or the structure of the recognition site. PMID- 1403797 TI - Human anti-cytochrome P450 antibodies in aromatic anticonvulsant-induced hypersensitivity reactions. AB - Aromatic anticonvulsants such as phenytoin, phenobarbital and carbamazepine are associated with a hypersensitivity syndrome (fever, rash lymphadenopathy, hepatitis) suggestive of an immune component. We have identified immunoglobulin G antibodies in the sera of nine affected patients which recognize a 53-kD protein which is constitutively expressed and PB inducible in rat liver microsomes. No such reactivity was observed in sera from healthy controls, patients on chronic phenytoin therapy without toxicity or patients with hepatic failure not receiving anticonvulsants. Using highly purified rat hepatic cytochrome P450, P450 3A1 was identified as the major antigenic species, whereas less intense reactivity was noted with P450 2C11. P450 2C6 and 3A2 were minor antigens in some patients. In all patients, the apparent constitutive and phenobarbital-inducible expression of the antigen was a composite effect of antibodies reacting with at least two isozymes, one of which was constitutively expressed and the other PB inducible. In human liver, a 53-kD antigen was expressed to a greater extent in microsomes from a patient with a fatal hepatotoxic reaction to phenytoin compared to microsomes from normal liver or from a sulfonamide hepatitis patient. Western blotting with microsomes prepared from lymphoblastoid cell lines transfected with different human hepatic cytochromes P450 failed to identify P450s 1A1, 1A2, 2A3, 2B6, 2C9, 2D6, 2E1, 3A4 or epoxide hydrolase as the target antigen. Identification of the antigen will be important in understanding the relationship between drug metabolism and the subsequent immune response in the pathogenesis of these rare but severe forms of drug toxicity. PMID- 1403798 TI - Regulation of cholecystokinin mRNA content in rat striatum: a glutamatergic hypothesis. AB - Changes in the cholecystokinin (CCK) mRNA content in rat striatum after the administration of specific glutamate and dopamine (DA) receptor agonists and antagonists were investigated. MK-801 (1 mg/kg i.p.), a selective noncompetitive N-methyl-D-aspartate (NMDA)-sensitive glutamatergic receptor antagonist, but not 6-cyano-7-nitroquinoxaline-2,3-dione (1.1-9.2 micrograms i.c.v.), a competitive non-NMDA glutamatergic receptor antagonist, produced a time- and dose-dependent decrease in striatal CCK mRNA. The maximum inhibition (50%) was observed after a daily treatment for 1 week with MK-801 (1 mg/kg). The activation of NMDA receptors by a single injection of NMDA (1.4 micrograms i.c.v.) elicited an 80% increase in CCK mRNA in rat striatum 8 hr after the injection. These data suggest that glutamate exerts a tonic regulation on striatal CCK mRNA, mainly through NMDA-sensitive glutamatergic receptors. B-HT 920, a DA D2 receptor agonist and benztropine, a DA uptake blocker, increased striatal CCK mRNA. This increase was partially blocked by the concomitant administration of MK-801. Moreover, the DA receptor antagonist haloperidol, at a dose that per se failed to change CCK mRNA (0.3 mg/kg i.p.), partially blocked the increase in CCK mRNA elicited by NMDA. Similarly, the NMDA effect was attenuated in rats with a 6-hydroxydopamine induced nigrostriatal lesion. Our findings suggest that in rat striatum a complex DA-glutamate interaction tonically regulates CCK expression via D2 and/or NMDA receptor activation. PMID- 1403799 TI - Gastroprotective effects of thromboxane receptor antagonists. AB - The recent discovery of potent, specific, long-acting thromboxane receptor antagonists, like SQ 33,961, mandated that studies be conducted to follow up an earlier study, which showed potential antiulcer activity of the short-acting thromboxane antagonist, SQ 28,668, in the taurocholic acid gastric erosion model in rats. In experiments conducted with the same taurocholic acid protocol, SQ 33,961 caused a dose-related reduction in taurocholate-induced gastric erosions, with an ID50 value of 12 micrograms/kg, i.p. In additional studies, aspirin and indomethacin were shown to produce gastric erosions in rats, and SQ 33,961 also inhibited gastric erosion in response to these anti-inflammatory drugs. The ID50 values were 0.24 and 0.26 mg/kg i.p. vs. aspirin (200 mg/kg, p.o.) and indomethacin (200 mg/kg, s.c.), respectively. The inhibition of aspirin-induced gastric injury by SQ 33,961 was confirmed histologically. This gastroprotective activity was not peculiar to SQ 33,961, because the structurally unrelated thromboxane receptor antagonist, BM 13,505, also significantly inhibited the development of aspirin-induced gastric lesions. In a more severe model, SQ 33,961 (10 mg/kg, i.p.) reduced gastric erosions by only 32% (not significant) 1 hr after ethanol ingestion (1 ml, p.o.) in rats. SQ 33,961 did not inhibit the antiphlogistic activity (carrageenan paw edema assay) of indomethacin, nor did it inhibit the analgesic activity (phenylquinone writhing assay) of aspirin. A dose of SQ 33,961 producing > or = 95% inhibition of nonsteroidal anti-inflammatory drug-induced gastric erosion (10 mg/kg, i.p.) produced a 37% reduction in the volume of gastric secretion without changing the titratable acidity of gastric contents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403800 TI - Suppression of hepatic drug metabolism by the interferon inducer, polyriboinosinic acid:polyribocitidylic acid. AB - Since the discovery that interferon inducers depress hepatic drug metabolism, the depressant action of cytochrome P450 (P450) has been demonstrated to be shared by cytokines such as interferon alpha/beta and interferon gamma as well as interleukin-1 and tumor necrosis factor. Because these cytokines are inflammatory mediators, it is not surprising that theophylline toxicity has been reported in patients with influenza B epidemic. Hence, to lay a foundation for studies of altered steroid and drug metabolism, the alteration of P450 isozymes was studied after polyriboinosinic acid:polyribocitidylic acid (poly I:poly C) administration. Twenty-four hours after poly I:poly C administration, hepatic P450 content decreased to 57% of control, whereas depression of other microsomal enzymes was less pronounced: P450 reductase (69%), cytochrome b5 (74%) and NADH cytochrome b5 reductase (85%). The depression of mRNA for cytochrome P450 1A1, 1A2, 2C11 and 2E1 was more than 60% of the controls. Recovery of mRNA levels was not complete within 72 hr. The changes in mRNAs, in general, paralleled alterations of monooxygenase activities and P450 isozyme content suggesting that the effect of poly I:poly C is pretranslational for all P450 isozymes studied. No overt differential effect on P450 isozymes was found after an administration of poly I:poly C. This study complements the previous report which demonstrated down regulation of mRNA for cytochrome P450 2C11 and 3A2. PMID- 1403801 TI - Effect of ambasilide, a new class III agent, on plateau currents in isolated guinea pig ventricular myocytes: block of delayed outward potassium current. AB - The actions of ambasilide (LU-47110) on the action potential and membrane currents of isolated guinea pig ventricular myocytes were studied using voltage clamp techniques. Ambasilide (1 microM) prolonged the action potential (APD) at 20, 50 and 90% repolarization by 11.2 +/- 4.3, 13.8 +/- 3.9 and 13.6 +/- 3.7%, respectively, compared to control (n = 10). APD prolongation was attributed to the block of delayed rectifier outward current (Ik) in a concentration-dependent fashion (0.01-10 microM). The effects on the APD and Ik were both partially reversed after perfusion with drug-free Tyrode's solution. The block of Ik by ambasilide was compared to that by E-4031 (5 microM), a putative selective blocker of that fast, inwardly rectifying component of Ik identified in guinea pig ventricle. E-4031 produced about 65% block of Ik for pulse durations between 80 and 420 msec, but the block decreased as the pulse duration increased further, the block accounting for 34 +/- 5% of Ik at 6.3 sec. In contrast, the percentage of reduction of Ik by 10 microM ambasilide did not produce a consistent magnitude of block over a similar range of short depolarizations, but rather progressively decreased Ik as the pusle duration lengthened. Block at the end of a 2-sec pulse was about 48 +/- 8%, more block than could be attributed to an E-4031-sensitive current block alone. Whereas E-4031 (5 microM) shifted the activation curve of Ik 10 mV toward positive potentials and decreased the slope factor, k, by about 4 mV, ambasilide (5 microM) had no effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1403802 TI - Effect of thrombin on proliferation, contraction and prostaglandin production of rat glomerular mesangial cells in culture. AB - The effect of thrombin on mesangial cell function was investigated. Thrombin caused a dose-dependent increase in [3H] thymidine incorporation (EC50 = 0.36 +/- 0.09 U/ml), intracellular calcium [(Ca++)i] mobilization (EC50 = 1.9 +/- 0.5 U/ml) and prostaglandin E2 (PGE2) production (EC50 = 0.25 +/- 0.02 U/ml) in rat glomerular mesangial cells. These effects were blocked by the thrombin inhibitor, hirudin (KB = 10.4 +/- 0.2 nM). The role of (Ca++)i mobilization and arachidonate metabolism in thrombin-stimulated proliferation was tested by the addition of the calcium channel blocker, nifedipine, and the cyclooxygenase inhibitor, indomethacin, to mesangial cell cultures. Indomethacin, at doses that completely inhibited the thrombin-mediated production of PGE2, had no significant effect on proliferation. The Ca++ channel blocker, nifedipine, inhibited both PGE2 production and [3H] thymidine incorporation in a dose-dependent fashion, but only at concentrations considered nonspecific. In addition to its effects on PGE2, thymidine incorporation and Ca++ mobilization, thrombin caused mesangial cell contraction as determined by a substrate distortion technique. This effect was not inhibited by indomethacin. These results indicate that thrombin can alter mesangial cell function in vitro. PMID- 1403803 TI - Renal organic acid transport: uptake by rat kidney slices of a furan dicarboxylic acid which inhibits plasma protein binding of acidic ligands in uremia. AB - The furan dicarboxylic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (5 propyl FPA), accumulates in uremic plasma and inhibits the binding of various drugs and marker ligands that are organic acids. 5-Propyl FPA is excreted unchanged in human urine and active tubular secretion is likely to be involved because of its high affinity for albumin. The uptake of 5-propyl FPA by rat kidney slices has been measured and compared with that of p-aminohippurate (PAH). The mean (+/- S.D.) slice/medium ratio for uptake of 5-propyl FPA (76 microM) was 22.7 +/- 2.6 (n = 11) and for PAH (75 microM) was 15.9 +/- 3.2 (n = 9) after incubation for 90 min at 25 degrees C. 5-Propyl FPA (149-829 microM) inhibited the uptake of PAH (77 microM) in a concentration-dependent manner, and likewise, PAH (150-830 microM) inhibited the uptake of 5-propyl FPA (77 microM). The mean apparent Km and Vmax values for the uptake of 5-propyl FPA were 194 +/- 125 microM and 55 +/- 28 nmol/g kidney/min, respectively, and 487 +/- 179 and 99 +/- 46 nmol/g kidney/min, respectively, for PAH. The kinetics of inhibition of uptake of PAH by 5-propyl FPA were mainly competitive. 5-Propyl FPA is thus likely to undergo active tubular secretion in a similar way to PAH, and this furan dicarboxylic acid, therefore, has the potential to inhibit the renal excretion of various drugs, drug conjugates and other endogenous organic acids. PMID- 1403804 TI - Mechanism for the hepatotoxicity of the antiandrogen, nilutamide. Evidence suggesting that redox cycling of this nitroaromatic drug leads to oxidative stress in isolated hepatocytes. AB - The nitroaromatic drug nilutamide has been shown previously to undergo redox cycling in aerobic rat liver microsomes, being reduced by NADPH-cytochrome P-450 reductase to a nitro anion-free radical which reacts with oxygen, to regenerate the parent drug, and form a superoxide anion dismuted to hydrogen peroxide. In the present study, the effects of nilutamide on isolated rat hepatocytes have been determined. After 6 and 8 hr of incubation with 0.5 mM nilutamide, lactate dehydrogenase was released in the incubation medium, and cell viability was decreased markedly. Consistent with a redox cycle producing reactive oxygen species, nilutamide increased nonmitochondrial (cyanide-resistant) oxygen consumption; the toxicity of nilutamide occurred sooner and was more extensive in the presence of sodium azide (an inhibitor of catalase). Consistent with an oxidative stress, the toxicity of nilutamide was associated with depletion of reduced glutathione, increased levels of glutathione disulfide, increased Ca(++) dependent phosphorylase a activity, oxidation and accumulation of cytoskeleton associated proteins and formation of blebs; toxicity was prevented by glutathione precursors, thiol reductants and/or antioxidants, such as L-cystine, L-cysteine, N-acetyl-L-cysteine, dithiothreitol, N,N'-diphenyl-p-phenylene-diamine and alpha tocopherol. Feeding the animals with a diet supplemented with 2% L-cystine increased the initial glutathione stores of hepatocytes and prevented nilutamide toxicity. It is concluded that nilutamide is toxic to isolated rat hepatocytes, as a probable consequence of an oxidative stress due to the redox cycling of this nitroaromatic compound. PMID- 1403805 TI - Flavonoid potentiation of contractile responses in rat blood vessels. AB - Certain bioflavonoids and phenolic compounds have long been known to enhance catecholamine responses, in vivo and in vitro. In the present studies the flavone, baicalein, potentiated nerve-stimulated contractions in vitro in rat tail and femoral artery isometric ring preparations. Inhibition of catecholamine reuptake with cocaine or catecholamine metabolism with tropolone and parglyine (monoamine oxidase and catecholamine-O-methyl transferase inhibitors, respectively) did not alter baicalein's ability to potentiate contractile responses to nerve stimulation. Baicalein (10(-5) M), the prototype flavone, also increased sensitivity to exogenous norepinephrine, serotonin, arginine vasopressin and to the noncatecholamine alpha-1 and alpha-2 adrenergic agonists, cirazoline and tramazoline. Structure-function studies indicated that flavone potentiation required three contiguous A or B ring hydroxylations. Several nonflavone phenol derivatives with three contiguous hydroxyls also potentiated nerve stimulation responses. As baicalein is a potent lipoxygenase inhibitor, comparisons were made between potentiating ability and lipoxygenase inhibitory activity in a series of flavonoids. There was no direct correlation between inhibition of 12-hydroxy-5,8,10,14-eicosatetraenoic acid levels in thrombin stimulated human platelets and potentiation of contractile responses in the femoral artery. Additionally, the specific substrate analog lipoxygenase inhibitor, 5,8,11-eicosatriynoic acid, and the cyclooxygenase inhibitor, ibuprofen, were nonpotentiating. Ibuprofen pretreatment did not alter the potentiating action of baicalein. It is concluded that flavonoids with three contiguous hydroxyls on either the A or B ring increase in vitro vascular responsiveness via a post-synaptic process, independent of cyclooxygenase, lipoxygenase, monoamine oxidase or catecholamine-O-methyl transferase activity. PMID- 1403806 TI - Hemodynamic effects of GI 87084B, an ultra-short acting mu-opioid analgesic, in anesthetized dogs. AB - Hemodynamic effects of GI 87084B, a novel ultra-short acting mu-opioid agonist, were studied in anesthetized dogs. In these studies, GI 87084B (0.3-20 nmol/kg/min i.v.) produced dose-dependent decreases in heart rate, arterial blood pressure, +dP/dt and cardiac output. Alfentanil produced similar effects but was less potent. After termination of the infusions (397 nmol/kg cumulative dose), the hemodynamic effects of GI 87084B dissipated over 30 to 40 min. The effects of alfentanil, however, persisted throughout the 60-min recovery period. Infusion of GI 87084B at lower dose rates (0.001-0.3 nmol/kg/min) in barbiturate-anesthetized dogs showed a threshold dose of 0.1 to 0.3 nmol/kg/min for effects on hemodynamic variables. After infusing 0.3 nmol/kg/min of GI 87084B for 10 min, hemodynamic variables recovered rapidly (10-20 min). Boli of GI 87084B (0.3-100 nmol/kg i.v.) produced dose-dependent decreases in the same hemodynamic variables. The duration of these effects increased from 5 to 20 min at 3 nmol/kg to 15 to 45 min at 100 nmol/kg. Naloxone (0.063 mg/kg/hr) decreased the magnitude and duration of the effects of GI 87084B, suggesting that these effects are mediated through opioid receptors. In summary, GI 87084B produced hemodynamic effects consistent with mu opioid agonism when administered by infusion or bolus, but these effects were brief in duration compared to other opioids. PMID- 1403807 TI - Synergism in the autonomic regulation of parotid secretion of protein in sheep. AB - 1. Stimulation of the cervical sympathetic nerve continuously at 2 Hz, or in bursts of 1 s at 20 Hz every 10 s, for 5 min doubled the resting flow of parotid secretion in anaesthetized sheep and increased its concentration of protein. It also caused a significant increase in the concentration of potassium and decreased that of sodium: these latter effects were linearly inversely related. 2. Stimulation of the parotid nerves (the parasympathetic innervation) continuously at 2 Hz increased the flow of parotid secretion over 15-fold which was significantly more than that which occurred in response to stimulation in bursts at 20 Hz. However, the latter pattern of stimulation significantly increased the concentration of protein in the saliva, which was not altered by stimulation at 2 Hz continuously. 3. Simultaneous stimulation of both the parotid and sympathetic nerves at 20 Hz in bursts substantially increased the output of protein from the gland, above that recorded in response to stimulation of either alone, without potentiating either the volume of secretion produced or the outputs of sodium or potassium. 4. The output of protein was also potentiated when both nerves were stimulated simultaneously at 2 Hz continuously but this pattern of stimulation elicited the secretion of a significantly smaller amount of protein. 5. All parotid responses to stimulation of the parotid nerves, either continuously at 2 Hz or in bursts at 20 Hz, were abolished by atropine (greater than or equal to 0.5 mg kg-1 I.V.), as was potentiation of protein secretion during combined stimulation with the sympathetic innervation. 6. Stimulation of the parotid nerves in bursts at a higher frequency (60 Hz for 1 s at 20 s intervals) elicited a sparse flow of parotid saliva in atropinized animals without significant increase in protein output, with or without simultaneous stimulation of the sympathetic innervation. 7. The results of these experiments show that secretion of protein by the parotid gland, in response to stimulation of the parasympathetic innervation, depends on the pattern of stimulation and is potentiated by concomitant stimulation of the sympathetic innervation in anaesthetized sheep. PMID- 1403808 TI - Mediation by nitric oxide of neurogenic relaxation of the urinary bladder neck muscle in sheep. AB - 1. Mechanical recordings were made in vitro from circularly oriented strips of the bladder neck muscle of sheep. In the absence of drugs, electrical field stimulation at frequencies of 0.2-1 Hz evoked clear-cut relaxations throughout 1 min stimulation periods, while higher stimulus frequencies (2-8 Hz) evoked variable responses consisting of relaxation, contraction or a mixture of both. All of the responses were abolished by tetrodotoxin (10(-6) M). 2. The contractions were reduced by guanethidine (10(-6) M) and atropine (10(-6) M), so that in the presence of these drugs clear-cut relaxations were obtained at 0.2-8 Hz stimulation, indicating that the relaxations were mediated by non-adrenergic, non-cholinergic (NANC) nerves. 3. The NANC relaxations were blocked by L-NG nitro arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. The antagonism by L-NAME was reversed by L-arginine. 4. Another feature of the NANC relaxation was 'rebound contraction' which occurred when the stimulus was switched off. The rebound contraction was also blocked by L-NAME and restored by L-arginine. 5. The relaxations and rebound contractions were unaffected by either alpha,beta-methylene ATP (10(-5) M) or 2-methylthio ATP (10(-5) M). 6. S-Nitroso L-cysteine, a substance which spontaneously releases NO at physiological pH, mimicked the relaxation and rebound contraction produced by nerve stimulation. 7. It is concluded that nerve-evoked relaxation of the bladder neck is mediated by NO, or a closely related substance such as S-nitroso-L-cysteine. PMID- 1403809 TI - Kinetic and pharmacological properties of the M-current in rodent neuroblastoma x glioma hybrid cells. AB - 1. The M-like current IK(M,ng) in differentiated NG108-15 mouse neuroblastoma x rat glioma hybrid cells has been studied using tight-seal, whole-cell patch-clamp recording. 2. When calculated from steady-state current-voltage curves, the conductance underlying IK(M,ng) showed a Boltzmann dependence on voltage with half-activation voltage Vo = -44 mV (in 3 mM [K+]) and slope factor (a) = 8.1 mV/e-fold increase in conductance. In 12 mM [K+] Vo = -38 mV and a = 6.9 mV. The deactivation reciprocal time constant accelerated with hyperpolarization with slope factor 17 mV/e-fold voltage change. 3. The reversal potential for deactivation tail currents varied with external [K+] as if PNa/PK were 0.005. 4. Steady-state current was increased on removing external Ca2+. In the presence of external Ca2+, reactivation of IK(M, ng) after a hyperpolarizing step was delayed. This delay was preceded by an inward Ca2+ current, and coincided with an increase in intracellular [Ca2+] as measured with Indo-1 fluorescence. Elevation of intracellular [Ca2+] with caffeine also reduced IK(M, ng). 5. IK(M, ng) was inhibited by external divalent cations in decreasing order of potency (mM IC50 in parentheses): Zn2+ (0.011) greater than Cu2+ (0.018) greater than Cd2+ (0.070) greater than Ni2+ (0.44) greater than Ba2+ (0.47) greater than Fe2+ (0.69) greater than Mn2+ (0.86) greater than Co2+ (0.92) greater than Ca2+ (5.6) greater than Mg2+ (16) greater than Sr2+ (33). This was not secondary to inhibition of ICa since: (i) inhibition persisted in Ca(2+)-free solution; (ii) La3+ did not inhibit IK(M, ng) at concentrations which inhibited ICa; and (iii) organic Ca2+ channel blockers were ineffective. Inhibition comprised both depression of the maximum conductance and a positive shift of the activation curve. Addition of Ca2+ (10 microM free [Ca2+]) or Ba2+ (1 mM total [Ba2+]) to the pipette solution did not significantly change IK(M, ng). 6. IK(M, ng) was reduced by 9-amino 1,2,3,4-tetrahydroacridine (IC50 8 microM) and quinine (30 microM) but was insensitive to tetraethylammonium (IC50 greater than 30 mM), 4-aminopyridine (greater than 10 mM), apamin (greater than 3 microM) or dendrotoxin (greater than 100 nM). 7. IK(M, ng) was inhibited by bradykinin (1-10 microM) or angiotensin II (1-10 microM), but not by the following other receptor agonists: acetylcholine (10 mM), muscarine (10 microM), noradrenaline (100 microM), adrenaline (100 microM), dopamine (100 microM), histamine (100 microM), 5-hydroxytryptamine (10 microM), Met-enkephalin (1 microM), glycine (100 microM), gamma-aminobutyric acid (100 microM) or baclofen (500 microM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403810 TI - The effects of a high sodium diet on the metabolism and secretion of vasoactive intestinal peptide in the rabbit. AB - 1. In view of previous observations that the metabolism of vasoactive intestinal peptide (VIP) is significantly increased in sodium-depleted rabbits, we wished to determine whether a high sodium intake also leads to alterations in VIP metabolism. We performed metabolic clearance studies in rabbits maintained on a high sodium diet and normal control diets. These studies were performed both before and after the administration of 1.5 mmol kg-1 of sodium intravenously to observe the effects of an acute increase in body sodium. 2. The rabbits maintained on the high sodium diet had a significantly lower basal plasma VIP level (P less than 0.025), a lower metabolic clearance rate (MCR) of the peptide (P less than 0.025) and a lower secretion rate (P less than 0.005), compared with the normal control animals. These differences were maintained following the intravenous sodium infusion. 3. The administration of the intravenous sodium infusion resulted in a further decrease in MCR in the rabbits on the high sodium diet (P less than 0.05). 4. These results confirm that VIP metabolism is affected by high dietary intake of sodium, as well as a low sodium intake, adding further support to the hypothesis that VIP may be involved in sodium homeostasis. PMID- 1403811 TI - Elevated muscle glycogen and anaerobic energy production during exhaustive exercise in man. AB - 1. The effect of elevated muscle glycogen on anaerobic energy production, and glycogenolytic and glycolytic rates was examined in man by using the one-legged knee extension model, which enables evaluation of metabolism in a well-defined muscle group. 2. Six subjects performed very intense exercise to exhaustion (EX1) with one leg with normal glycogen (control) and one with a very high concentration (HG). With each leg, the exhaustive exercise was repeated after 1 h of recovery (EX2). Prior to and immediately after each exercise bout, a muscle biopsy was taken from m. vastus lateralis of the active leg for determination of glycogen, lactate, creatine phosphate (CP) and nucleotide concentrations. Measurements of leg blood flow and femoral arterial-venous differences for oxygen content, lactate, glucose, free fatty acids and potassium were performed before and regularly during the exhaustive exercises. 3. Muscle glycogen concentration prior to EX1 was 87.0 and 176.8 mmol (kg wet wt)-1 for the control and HG leg, respectively, and the decreases during exercise were 26.3 (control) and 25.6 (HG) mmol (kg wet wt)-1. The net glycogen utilization rate was not related to pre exercise muscle glycogen concentration. Muscle lactate concentration at the end of EX1 was 18.8 (control) and 16.1 (HG) mmol (kg wet wt)-1, and the net lactate production (including lactate release) was 26.5 (control) and 23.6 (HG) mmol (kg wet wt)-1. Rate of lactate production was unrelated to initial muscle glycogen level. Time to exhaustion for EX1 was the same for the control leg (2.82 min) and HG leg (2.92 min). 4. Muscle glycogen concentration before EX2 was 14 mmol (kg wet wt)-1 lower than prior to EX1. During EX2 the muscle glycogen decline of 19.6 mmol (kg wet wt)-1 for the control leg was less than for the HG leg (26.2 mmol (kg wet wt)-1). The muscle lactate concentrations at the end of EX2 were about 7 8 mmol (kg wet wt)-1 lower compared to EX1, and the net lactate production was reduced by 40%. The exercise time during EX2 was 0.35 min shorter for the control leg, while no difference was observed for the HG leg. 5. Total reduction in ATP and CP was similar during the four exercise bouts, while a higher accumulation of inosine monophosphate (IMP) occurred during EX2 for the control leg (0.72 mmol (kg wet wt)-1) compared to the HG leg (0.20 mmol (kg wet wt)-1).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403812 TI - Reversal of the cross-bridge force-generating transition by photogeneration of phosphate in rabbit psoas muscle fibres. AB - 1. Orthophosphate (P(i), 0.1-2.0 mM) was photogenerated within the filament lattice of isometrically contracting glycerinated fibres of rabbit psoas muscle at 10 and 20 degrees C. The P(i) was produced by laser flash photolysis of the photolabile compound 1-(2-nitrophenyl)ethylphosphate (caged P(i)). Caged P(i) caused a depression of tension that was much smaller than that caused by P(i). 2. Photolysis of caged P(i) produced a decline in isometric force composed of four phases: phase I, a lag phase (e.g. 1-4 ms at 10 degrees C) during which force did not change; phase II, an exponential decline by as much as 20% of the pre-pulse force; phase III, a partial force recovery (0-3% of the pre-pulse force); and phase IV, a further slow (0.5-3 s) decline to the steady value. Phases I, III and IV were largely independent of [P(i)] and are likely to be indirect effects caused by the caged P(i) photolysis. 3. Both the rate and amplitude of phase II depended markedly on [P(i)]. The amplitude of phase II was similar to the reduction of steady-state force by P(i). The rate of phase II increased with increasing temperature and [P(i)]. At high [P(i)] the rate began to saturate, and approached limits of 123 s-1 at 10 degrees C and 194 s-1 at 20 degrees C. 4. The rate of phase II was independent of sarcomere overlap, while the amplitude was proportional to tension at partial filament overlap. A control experiment using caged ATP showed that phase II was not produced by the photolytic by-products or the light pulse. The results suggest that phase II is associated with the force generating transition of the cross-bridge cycle. 5. Sinusoidal length oscillations at 0.5 and 2 kHz were used to measure muscle stiffness during phase II. Stiffness declined in a single exponential phase, with the same time course as phase II of the tension transient. The change in stiffness was 83 +/- 6% (mean +/- S.E.M., n = 10, 0.5 kHz) of the change in tension when both signals were normalized to their pre-flash values. 6. Analysis of the data shows that two steps are involved in force generation and P(i) release. The non-force exerting AM-ADP-P(i) cross-bridge state first isomerizes to form a force-exerting cross bridge state (AM'-ADP-P(i)). P(i) is then released to form a second force generating state, AM'-ADP.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403813 TI - Sarcoplasmic reticulum buffering of myoplasmic calcium in bovine coronary artery smooth muscle. AB - 1. We tested the hypothesis that the sarcoplasmic reticulum (SR) buffers (attenuates) the increase in averaged myoplasmic free [Ca2+] (Ca(im)) resulting from Ca2+ influx. 2. Fura-2 measurements of Ca(im) were obtained in single smooth muscle cells freshly dispersed from bovine coronary artery. 3. Caffeine (5 x 10( 3) M) elicited a transient increase in Ca(im) and depleted the SR Ca2+ store. In the continued presence of caffeine or 10(-5) M-ryanodine SR buffering of Ca(im) was inhibited. Subsequent exposure to high extracellular [K+] (greater than 30 mM, equimolar Na+ removal) elicited a 2-fold more rapid and 2-fold greater peak increase in Ca(im) than high K+ elicited when SR buffering of Ca(im) was normal. The augmented increase in Ca(im) was inhibited 35% by 10(-5) M-diltiazem, 65% by 2 x 10(-4) M-LaCl3, and 87% in Ca(2+)-free external solution. 4. When Ca(im) buffering capacity was increased by partially depleting the SR with a transient (1 min) exposure to caffeine, subsequent exposure to 80 nM-K+ solution increased Ca(im) almost 2-fold more slowly than 80 mM-K+ before depletion of Ca2+ from the SR. However, the influxing Ca2+ was sequestered by the SR and refilled it, as evident by the subsequent caffeine-induced Ca(im) transient being identical to the first. Increasing extracellular [K+] (thus, increasing depolarization and Na+ removal) caused proportional increases in Ca(im) and the subsequent caffeine induced Ca(im) transients were proportionally larger, indicating a graded filling of the SR by Ca2+ influx. 5. Diltiazem (10(-5) M) inhibited the refilling of the SR achieved by 80 mM-K+, by 26%. Refilling was inhibited 76% by 80 mM-K+, Ca(2+) free solution, indicating the fraction of refilling dependent on influx of Ca2+ through voltage-gated Ca2+ channels, leak channels, and other influx pathways. Mild depolarization with 35 mM-K+ (no Na+ removal) often caused no increase in Ca(im), but influx through voltage-gated Ca2+ channels occurred because the SR Ca2+ store was refilled. Also, 10(-5) M-diltiazem or 10(-6) M-TA3090 inhibited the refilling to levels attributable only to leak influx of Ca2+. 6. All data support our hypothesis that the SR significantly attenuates the amount of Ca2+ influx that accumulates to increase Ca(im).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403814 TI - Unexpected role of the oblique muscles in the human vertical fusional reflex. AB - 1. If a weak vertically oriented prism is inserted before one eye, binocular single vision is restored by vertically divergent eye movements (one eye turning upward, the other downward); and it is usually assumed that the vertical rectus muscles mediate that fusional reflex. 2. When vertically divergent eye movements occur, both eyes also systematically rotate in parallel around their lines of sight (conjugate cyclotorsion). The direction of these unexpected eye movements demonstrates that they must be due to the oblique muscles, not the vertical recti. 3. The magnitude of these conjugate torsional movements is large enough to imply that the oblique muscles, in producing such torsion, would simultaneously effect all the divergent vertical re-orientation of the eyes required by the targets. 4. The cyclotorsion is accompanied by systematic translation of the eye along a nasal-temporal axis; the direction and extent of that non-rotational displacement indicate that the eye movements of the fusional reflex may well be mediated exclusively by the superior oblique muscles, acting against fixed tone in the inferior oblique muscles. 5. This revised understanding of the oculomotor co-ordination involved in the vertical fusional reflex has significant implications for both neurophysiology and oculomotor surgery. PMID- 1403815 TI - Comparison of the actions of adenosine at pre- and postsynaptic receptors in the rat hippocampus in vitro. AB - 1. Intracellular microelectrode recordings were used to study the cellular location, the receptor pharmacology, and the mechanism of action of adenosine on pyramidal cells and presynaptic axonal endings in area CA3 of organotypic hippocampal slice cultures. 2. Adenosine (bath applied at 50 microM) caused a 10 15 mV hyperpolarization of CA3 cells, as well as a 75-100% decrease in the amplitude of excitatory and polysynaptic inhibitory postsynaptic potentials (EPSPs and IPSPs). Adenosine had no effect on the amplitude of monosynaptic IPSPs elicited in the presence of excitatory amino acid receptor antagonists, but did reduce the amplitude of isolated EPSPs, elicited after blocking GABAA receptors and reducing subsequent epileptic bursts with excitatory amino acid receptor antagonists. These data indicate that adenosine receptors are located on excitatory, but not inhibitory, presynaptic elements. 3. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, bath applied at 200 nM) blocked the pre- and postsynaptic actions of adenosine. DPCPX had no effect on the amplitude of control synaptic responses, suggesting that there is no tonic activation of adenosine receptors in hippocampal slice cultures under control conditions. The A1 receptor agonists R-N6-phenylisopropyladenosine (R-PIA) mimicked all pre- and postsynaptic actions of adenosine. 4. Pertussis toxin pretreatment (500 ng/ml for 48 h) prevented adenosine from activating postsynaptic K+ conductance, but not from inhibiting EPSPs. In contrast, stimulation of protein kinase C with phorbol ester (phorbol 12, 13-dibutyrate, 1 microM for 10 min) reduced the presynaptic, but not the postsynaptic, actions of adenosine. 5. Barium (bath applied at 1 mM) blocked the adenosine-activated K+ conductance, but not the inhibition of isolated EPSPs by adenosine. 6. Adenosine at 0.03-1 microM reduced the frequency of, or blocked, spontaneous epileptiform bursting produced by bicuculline. DPCPX (200 nM) increased the rate of spontaneous bursting, consistent with a tonic activation of adenosine receptors during hyperactivity, and led to the development of prolonged ictal-like bursts, suggesting that the endogenous release of adenosine may contribute to the termination of epileptic bursts. 7. We conclude that adenosine acts at pre- and postsynaptic receptors which are pharmacologically indistinguishable. Postsynaptically, adenosine increases a barium-sensitive K+ conductance via a pertussis toxin-sensitive GTP-binding protein. The presynaptic action of adenosine must, however, be mediated by some other mechanism. PMID- 1403816 TI - Na(+)-HCO3- symport in the sheep cardiac Purkinje fibre. AB - 1. Intracellular pH (pHi) was recorded in isolated sheep cardiac Purkinje fibres using liquid sensor ion-selective microelectrodes in conjunction with conventional (3 M-KCl) microelectrodes (to record membrane potential). 2. In HEPES-buffered solution (pH0 7.4), pHi recovery from an intracellular acid load (20 mM-NH4Cl removal) was blocked by 1 mM-amiloride, consistent with the inhibition of Na(+)-H+ exchange. Replacement of the HEPES buffer with CO2-HCO3- caused a transient acidosis followed by an amiloride-resistant recovery of pHi to more alkaline levels (n = 43). This implies the presence of a HCO3(-)-dependent pHi regulatory mechanism. 3. Comparison of the membrane potential with the equilibrium potential for HCO3- ions (EHCO3) estimated during amiloride-resistant pHi recovery, showed that for polarized fibres (membrane potential Em approximately -80 mV), there was a net outward electrochemical driving force for HCO3- ions. Hence the amiloride-resistant pHi recovery cannot be explained in terms of passive HCO3- influx through membrane channels. 4. Removal of external Na+ (Na0+ replaced by N-methyl-D-glucamine) inhibited HCO3(-)-dependent pHi recovery, whereas removal of external Cl- (leading to depletion of internal Cl-; Cl0- replaced by glucuronate) or short-term removal of extracellular K+ had no inhibitory effect. We suggest that a Na(+)-HCO3- co-influx causes the recovery. Replacement of external Na+ with Li+ greatly reduced HCO3(-)-dependent pHi recovery indicating that Li0+ cannot readily substitute for Na0+ on the co transport. 5. The stilbene drug DIDS (4,4-diisothiocyano-stilbene-disulphonic acid, 500 microM) slowed HCO3(-)-dependent pHi recovery. 6. Depolarization of the membrane potential in high K0+ (44.5 mM) solution or with 5 mM-BaCl2 had no effect upon the rate of HCO3(-)-sensitive pHi recovery. This observation, when coupled with the fact that activation of HCO3(-)-dependent pHi recovery was associated with no consistent change of membrane potential, suggests that the Na(+)-HCO3- co-influx is electroneutral and voltage insensitive. 7. HCO3(-) dependent pHi recovery was unaffected by the Na(+)-K(+)-2Cl- co-transport inhibitor, bumetanide (150 microM). 8. The contribution of Na(+)-H+ exchange and Na(+)-HCO3- co-transport to net acid efflux was assessed. At a pHi of 6.6, we estimate that the co-transport should account for 20% of total acid equivalent efflux.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403817 TI - The electro-mechanical response of canine inspiratory intercostal muscles to increased resistance: the cranial rib-cage. AB - 1. The effect of graded increases in inspiratory airflow resistance on the electrical activity and the mechanical behaviour of the three groups of inspiratory intercostal muscles (parasternal intercostal, external intercostal, levator costae) situated in the cranial portion of the rib-cage has been studied in ten anaesthetized, spontaneously breathing dogs. The mechanical behaviour of the muscles was determined by measuring the respiratory changes in muscle length and the displacements of the rib. 2. During unloaded inspiration, the three muscles were active, the rib moved in the cranial direction, and the parasternal intercostal and levator costae muscles shortened; in most animals, the external intercostals shortened as well. 3. Graded increases in inspiratory airflow resistance elicited a progressive inhibition of parasternal intercostal activity and a gradual facilitation of external intercostal and levator costae activities. Concomitantly, the parasternal intercostals continued to shorten during inspiration. However, both the external intercostals and the levator costae progressively lengthened, and the rib was gradually displaced in the caudal direction. This pattern persisted after increases in chemical respiratory drive had developed. 4. Sectioning the phrenic nerve roots did not alter the electrical or the mechanical response of the parasternal intercostal muscles to loading, but it markedly affected the response of the external intercostals and levator costae. After phrenicotomy, the external intercostals and levator costae continued to shorten during loaded breaths, the rib continued to be displaced in the cranial direction, and although the rate of inspiratory muscle shortening and of rib motion decreased, the facilitation of external intercostal and levator costae activities was markedly reduced or abolished. 5. Lengthening of the external intercostals and caudal displacement of the rib was reproduced by isolated stimulation of the phrenic nerves. 6. The reflex facilitation of external intercostal and levator costae activities that takes place during inspiratory resistive loading thus results primarily from the collapsing action of the diaphragm on the cranial portion of the rib-cage and the consequent lengthening of these muscles. The mechanical effectiveness of this reflex facilitation, however, appears to be relatively small. PMID- 1403818 TI - The electro-mechanical response of canine inspiratory intercostal muscles to increased resistance: the caudal rib-cage. AB - 1. The effect of graded increases in inspiratory airflow resistance and airway occlusion on the electrical activity and the mechanical behaviour of the levator costae and external intercostal muscles situated in the caudal interspaces (zone of apposition of the diaphragm to the rib-cage) has been studied in spontaneously breathing dogs. 2. The external intercostal and levator costae muscles in the cranial interspaces were invariably active during unloaded inspiration and showed progressive facilitation of activity with increases in inspiratory resistance. In contrast, whether in the supine or in the prone position, the levator costae muscles of the caudal interspaces did not show any facilitation of activity, and the caudal external intercostal muscles never showed any inspiratory electrical activity, including during airway occlusion. 3. With graded increases in inspiratory airflow resistance, the cranial external intercostals demonstrated a gradual inspiratory lengthening and the cranial ribs were progressively displaced in the caudal direction. The caudal ribs, however, were invariably displaced in the cranial direction. As a result, the caudal external intercostals showed a progressive inspiratory shortening. 4. Shortening of the caudal external intercostals and cranial displacement of the caudal ribs were reproduced by isolated stimulation of the phrenic nerves. Thus, as inspiratory resistance increases, contraction of the diaphragm causes unloading, rather than loading, of the spindles present in the caudal external intercostal muscles. 5. After the phrenic nerves were sectioned, however, the caudal external intercostals invariably lengthened a substantial amount during inspiration, but they still did not show any inspiratory electrical activity. Accentuating the inspiratory lengthening of these muscles by external rib fixation and increasing the chemical respiratory drive did not elicit any inspiratory electrical activity either. The alpha-motoneurones of the external intercostal muscles in the caudal interspaces thus have very small central respiratory drive potentials with respect to their critical firing threshold. PMID- 1403819 TI - Role of cholecystokinin in the inhibition of gastric acid secretion in dogs. AB - 1. This study was designed to determine the involvement of cholecystokinin (CCK) in the gastric secretory responses to exogenous and endogenous secretagogues in conscious dogs with chronic gastric fistulae (GF), pancreatic fistulae (PF) and Heidenhain pouches (HP). 2. A meal of meat or intragastric application of peptone (300 mosM) increased secretion of HCl from the HP and pancreatic secretion of protein and plasma levels of gastrin, CCK and somatostatin. 3. The CCK receptor antagonist L-364,718 caused a further increase in the postprandial HCl secretion from the HP and in the plasma levels of gastrin and CCK but pancreatic output of protein and plasma concentration of somatostatin were significantly reduced. 4. Addition to intragastric peptone of 10% oleate or its acidification to pH 3.0 profoundly inhibited the HP secretion and gastrin release but significantly increased pancreatic secretion of protein and plasma levels of CCK and somatostatin. Administration of L-364,718 reversed the fall in the HP secretion and plasma gastrin while significantly attenuating pancreatic protein secretion and plasma somatostatin levels. 5. Intragastric administration of hyperosmolar (1200 mosM) peptone also inhibited HCl secretion from the HP but this was not affected by L-364,718. 6. Exogenous CCK and bombesin (but not gastrin) caused a small increase in HCl secretion from the HP and marked stimulation of pancreatic protein secretion accompanied by a significant rise in plasma levels of gastrin, CCK and somatostatin. Administration of L-364,718 resulted in a further increase in the HCl response of HP to bombesin and in plasma levels of gastrin and CCK but caused a reduction in plasma levels of somatostatin. 7. We conclude that CCK released by a meal of meat, intragastric peptone, oleate or acidified peptone and intravenous bombesin exerts tonic inhibitory influences on gastric acid secretion and that this effect is mediated, at least in part, by somatostatin. PMID- 1403820 TI - Spontaneous sarcoplasmic reticulum calcium release and extrusion from bovine, not porcine, coronary artery smooth muscle. AB - 1. We tested the hypothesis that the Ca(2+)-loaded sarcoplasmic reticulum (SR) of coronary artery smooth muscle spontaneously releases Ca2+ preferentially toward the sarcolemma to be extruded from the cell without increasing the average free myoplasmic [Ca2+] (Ca(im)) concentration. 2. The SR of bovine cells was Ca(2+) loaded by depolarization-induced Ca2+ influx. Release (unloading) of Ca2+ from the SR during recovery from depolarization was determined by Fura-2 microfluorometry of Ca(im). The SR Ca2+ unloading was maximal following a long (14 min) recovery from depolarization, as shown by the 66% decrease in the peak caffeine-induced Ca(im) transient compared to the Ca(im) transient after a short (2 min) recovery. No increase in Ca(im) occurred during the long recovery. No unloading of the SR Ca2+ store was noted in porcine cells. 3. Approximately 80% of the outward K+ current in bovine and porcine cells was sensitive to subsarcolemmal Ca2+ (Ca(is)) concentrations. Whole-cell voltage clamp using pipette solutions with Ca2+ concentrations clamped between 0 and 1000 nM with Ca(2+)-EGTA or Ca(2+)-BAPTA buffers showed increasing K+ currents (normalized for cell membrane surface area) as a function of both membrane potential and Ca(is). Clamping of Ca(im) and Ca(is) was verified by the lack of changes in K+ current and Fura-2 ratio in response to Ca2+ influx, Ca(2+)-free external solution, or caffeine-induced Ca2+ release. At +30 to +50 mV the K+ current amplitude showed a similar sensitivity to Ca2+ as Fura-2. These data indicate that in this experimental preparation Ca(2+)-activated K+ current is a valid estimate of Ca(is). 4. Simultaneous Ca(im) and Ca(is) measurements in bovine cells which were not Ca(2+)-clamped (2 x 10(-4) M-EGTA pipette solution) showed that during the long recovery period the K+ current (reflecting Ca(is)) increased 55%, while Ca(im) did not change. 5. In quiescent bovine cells the Ca(is) was higher than Ca(im), while the higher resting Ca(is) gradient was not apparent in porcine cells. 6. The Ca(is) concentration was directly related to the amount of Ca2+ in the SR in bovine, but not porcine cells. Depletion of the SR in bovine cells by caffeine resulted in a 58% decrease in K+ current compared to the resting K+ current. 7. Caffeine-induced Ca2+ release caused an increase in Ca(is) which preceded the increase in Ca(im) by approximately 2 s.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403821 TI - Alpha-melanocyte-stimulating hormone suppresses fever and increases in plasma levels of prostaglandin E2 in the rabbit. AB - 1. The effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on changes in body temperature and plasma levels of prostaglandin E2 (PGE2) were measured in the rabbit following intravenous injection of bacterial lipopolysaccharide (LPS), rabbit endogenous pyrogen (EP), human recombinant tumour necrosis factor-alpha (TNF-alpha), human recombinant interleukin-1 beta (IL-1 beta) and intracerebroventricular injection of PGE2. 2. LPS (25 ng kg-1), EP (25 microliters kg-1), TNF-alpha (11 micrograms kg-1) and IL-1 beta (5 ng kg-1) produced increases in body temperature simultaneously with increases in plasma PGE2 levels. alpha-MSH (5 or 10 micrograms kg-1) attenuated both the increase in body temperature and increases in plasma levels of PGE2. 3. Intracerebroventricular injection of PGE2 (500 ng) produced a monophasic increase in body temperature. alpha-MSH (5 micrograms kg-1) administered 20 min after PGE2 had no effect on the hyperthermic response. 4. alpha-MSH (10 micrograms kg-1) had no effect on either body temperature or plasma levels of PGE2 in response to I.V. injection of sterile saline. 5. These data demonstrate that alpha-MSH inhibits both the pyrogenic actions of LPS, EP, TNF-alpha and IL-1 beta and their ability to increase PGE2 release without affecting the direct actions of PGE2, suggesting the possibility that alpha-MSH may prevent the synthesis of PGE2 either by preventing the actions or release of mediators such as TNF-alpha and IL-1 in response to LPS. PMID- 1403822 TI - Mechanical properties of skinned rabbit psoas and soleus muscle fibres during lengthening: effects of phosphate and Ca2+. AB - 1. Mechanical properties of permeabilized single fibres from rabbit psoas and soleus muscle were determined by measuring the length responses due to abrupt changes in load and the force responses due to isovelocity length changes at different phosphate and Ca2+ concentrations. 2. The length responses due to abrupt increases in load from psoas fibres showed a rapid lengthening during the change in load followed by a phase of lengthening during which the velocity gradually decreased. In soleus fibres an abrupt lengthening during the change in load was followed by a phase of lengthening during which the velocity remained constant or decreased slightly for increases in load to less than 1.45 of the isometric force (F0). For larger increases in load the velocity during this later phase first increased and thereafter decreased. 3. The initial force-velocity curve, derived from the early part of the isotonic responses after the change in load, as well as the late force-velocity curve derived from the force level attained during isovelocity length changes, were sensitive to phosphate. Phosphate caused a shift of the absolute force-velocity curves of both psoas and soleus fibres towards lower values of force. In psoas fibres, the relative force velocity curves derived by normalization of the force level to the force developed isometrically was shifted by phosphate to smaller velocities. In soleus fibres, the initial velocity at low and intermediate relative loads (less than 1.75 F0) was increased by phosphate but at higher loads it decreased, while the late force-velocity curve showed an overall decrease in velocity. 4. The force responses during isovelocity lengthening of psoas fibres showed an early rapid increase in force followed by a slow rise in force. The position of this break point in force was sensitive to the phosphate concentration. In soleus fibres, the force responses without phosphate showed an overshoot followed by a slow rise in force. The overshoot diminished with increasing phosphate concentration. 5. Phosphate and Ca2+ affected the force responses in psoas and soleus fibres in different ways. When the isometric starting levels were the same, force during and after the length change at submaximal activation was always less than at maximal activation in the presence of 15 mM-phosphate. 6. The changes in the mechanical performance during lengthening caused by phosphate in psoas as well as in soleus fibres, are in agreement with a decrease in the average force per attached crossbridge.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403823 TI - Properties of spontaneous inward currents recorded in smooth muscle cells isolated from the rabbit portal vein. AB - 1. Characteristics of spontaneous transient inward currents (STICs) which produced membrane depolarization were analysed with the perforated patch technique in single smooth muscle cells isolated from the rabbit portal vein. 2. In K(+)-free solutions the amplitude of STICs was linearly related to membrane potential and the reversal potential (Er) was -3.0 +/- 0.9 mV. Replacement of external NaCl with NaI shifted Er to -40.0 +/- 1.0 mV. Substitution of external NaCl by NaSCN also moved Er to negative values but replacement of sodium with Tris and choline did not change Er. It is concluded that STICs are generated by an increase in chloride conductance. 3. STICs were abolished or reduced by the chloride channel antagonists anthracene-9-carboxylic acid (1 mM) and 4-acetamido 4'-isothiocyanato-2,2'- stilbene-disulphonic acid (2 mM). 4. STICs were blocked by noradrenaline and caffeine which deplete intracellular calcium stores. This effect was reversible and this result indicates that the primary trigger for STICs is calcium released from intracellular stores and therefore STICs are calcium-activated chloride currents (ICl(Ca)). 5. Removal of calcium from the bathing solution abolished STICs in six out of seven cells but STICs persisted in Ca(2+)-free solution in one cell. When STICs were abolished in Ca(2+)-free external solution the size of the internal calcium store, as estimated from the noradrenaline-induced ICl(Ca), was not altered. It appears that an influx of calcium is usually necessary for STICs to be observed. 6. The frequency and amplitude of STICs were not altered by the voltage-dependent calcium channel antagonist cadmium (1 mM). However, in some quiescent cells influx of calcium through voltage-dependent channels did activate STICs. 7. It was concluded that in isolated portal vein cells STICs represent a Ca(2+)-activated chloride current which leads to spontaneous depolarization of the membrane and may play an important physiological or pathophysiological role to produce smooth muscle contraction. PMID- 1403824 TI - Ectopic activity in demyelinated spinal root axons of the rat. AB - 1. We have provoked ectopic discharges from demyelinated rat spinal roots by applying 1 mM-4-aminopyridine (4-AP), and recorded membrane currents and action potentials extracellularly by spike-triggered averaging. The demyelination was caused by intrathecal injection of diphtheria toxin, 6-9 days previously. 2. Mapping the distribution of membrane currents in the vicinity of an ectopic site showed that in most cases (eight out of twelve recorded) the impulses arose from one end of a continuously conducting internode, and conducted in both directions. In the remaining cases the impulses also arose from a site of demyelination. 3. The 4-AP-induced activity resembled the activity occurring spontaneously in some preparations, and was often highly regular (5-20 Hz). Recordings of membrane potential revealed a pacemaker potential, which was localized to the site of impulse initiation. One ectopic site was tested with applied currents and found to have a linear current-frequency relation for steady currents. 4. The time course of the pacemaker potential resembled that of the small after hyperpolarization seen in normal fibres, due to a slow K+ conductance (GKs). Tetraethylammonium and barium ions, which block GKs, made spontaneously active fibres fire much more rapidly, or to fire bursts of action potentials. 5. Possible mechanisms for these ectopic discharges are discussed. GKs appears to contribute to the pacing of the activity, but not its generation. The increased excitability of the active fibres could not be attributed directly to the loss of myelin, nor to extracellular K+ accumulation. We suggest that they may have been depolarized by stretch-activated or ligand-gated channels in the demyelinated axon membrane. PMID- 1403825 TI - Unitary A-currents of rat locus coeruleus neurones grown in cell culture: rectification caused by internal Mg2+ and Na+. AB - 1. We have used whole-cell and single-channel recording to study the transient outward potassium current (A-current) of rat locus coeruleus neurones grown in tissue culture. The A-current was largely inactivated at the resting potential, but could be activated from sufficiently negative holding potentials during steps positive to -50 mV. The current was sensitive to 4-aminopyridine. Another slowly activating, sustained current was similar to a delayed rectifier. 2. In the on cell configuration the unitary conductance of channels carrying A-current was 40.9 +/- 2.2 pS (n = 6) with high external potassium (140 mM) and 14.8 +/- 1.4 pS (n = 11) with 3 mM [K+]o. The unitary current-voltage relation was not linear, but had a negative slope at very positive voltages in 3 mM [K+]o. The reversal potential changed with [K]o as expected for a K+ channel. 3. The open state probability of A-current channels was voltage dependent, reaching a peak of 0.78 +/- 0.17 (seven patches). The relationships between both activation and inactivation and membrane potential were well fitted by Boltzmann expressions. Activation was half-maximum at a potential 71.9 +/- 11.8 mV (n = 4) positive to the resting potential (approximately -61 mV). Inactivation was half-complete 29.4 +/- 3.8 mV (n = 4) negative to the resting potential. There was evidence from runs analysis for slow inactivation of channels. 4. Channels showed frequent visits to substates, the most readily identifiable of which had an amplitude 0.55 +/- 0.04 (n = 5) of the fully open state. Other substates had amplitudes of around 0.25 and 0.75. Occupancy of substates was greater at negative membrane potentials. 5. A preliminary analysis of kinetic behaviour, treating visits to substates as openings, shows that open times are distributed as a single exponential. The open time was 16.2 ms (n = 4) at a voltage 100 mV positive to the resting potential, increasing with further depolarization. Closed times are distributed as the sum of three or four exponentials. First latency distributions are strongly voltage dependent and show a delay, giving a sigmoidal rise to the distribution. Increasing temperature increased unitary current and reduced mean open time. 6. The mechanism of the rectification seen in the unitary current voltage relationship was examined using excised, inside-out patches.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403826 TI - Effect of perfusion pressure on force of contraction in thin papillary muscles and trabeculae from rat heart. AB - 1. Increased coronary perfusion leads to increased myocardial contraction and oxygen consumption (Gregg's phenomenon) even when oxygen supply is presumably sufficient. Previous studies concerned whole hearts, however, in which local hypoxia may play a role. We developed techniques for internal perfusion of thin papillary muscles from rat heart. The influence of perfusion pressure on muscle contraction was studied. We investigated whether Gregg's phenomenon is due to (a) hypoxia, (b) stretch of the muscle fibres, or (c) increased contractility. 2. The effectiveness of the perfusion technique was demonstrated in four ways: (a) the diameter of the capillaries increased with perfusion pressure; (b) 14 +/- 4% (mean +/- S.D., n = 11) increase in muscle diameter was observed on a change of perfusion pressure from 0 to 50 cmH2O; (c) addition of India ink to the perfusate caused rapid staining of the entire muscle; (d) during internal perfusion and external superfusion peak force was mainly determined by the [Ca2+] in the internal perfusate. 3. An increase of perfusion pressure from 0 to 70 cmH2O induced 74 +/- 20% (mean +/- S.D., n = 11) increase in peak force of contraction. In the absence of internal perfusion peak force was not affected by approximately 50% reduction of the PO2 in the bathing solution (from 700 to 350 mmHg). Hence, oxygen supply was not a limiting factor, i.e. the effect of internal perfusion on force was not related to hypoxia. 4. Segment length was measured with markers attached to the surface of the muscle. Perfusion-induced changes in segment length were negligible (-0.2 +/- 1.5%, n = 11). Force-length relationships at different perfusion pressures show that the perfusion-induced increase in force was generally larger than the maximum increase in force that could be induced by stretch. Furthermore, the time course of stretch and perfusion effects on force was different. We conclude that Gregg's phenomenon is not related to changes in fibre length, i.e. the hypothesis of pressure-induced stretch ('garden hose' effect) does not apply to papillary muscles. 5. The pressure-induced changes in the force-length relationship were similar to the changes obtained with interventions that increase contractility, such as increased [Ca2+]. 6. Since hypoxia and length effects were not involved, and the effect of perfusion pressure was similar to that of inotropic interventions, we conclude that Gregg's phenomenon is a change in contractility. Possible explanations include changes in the ionic composition or volume of the interstitium, and inotropic factors produced by the endothelium or intramyocardial neurons. PMID- 1403827 TI - Compared effects of serotonin on cervical and hypoglossal inspiratory activities: an in vitro study in the newborn rat. AB - 1. Experiments were performed on the brain stem-spinal cord preparation of newborn rats, in which the phrenic and hypoglossal nerves continue to show rhythmic respiratory activity in vitro, in order to compare the effects of serotonin (5-HT) on both activities and to analyse the mechanisms responsible for the depression by 5-HT of the hypoglossal activity. 2. Under control conditions, simultaneous recordings of the inspiratory discharges of hypoglossal and cervical roots showed that the two bursts did not start simultaneously and had different patterns (time-to-peak and peak values); this suggests that both pools of motoneurons did not share the same central drive(s). 3. Adding 5-HT and related agents to the bathing medium delayed and depressed the hypoglossal inspiratory discharge via activation of 5-HT2 receptors since these effects were elicited by 5-HT2 agonists (alpha-methyl-5-HT and 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane-HCl (DOI)) but not by 5-HT1 agonists (RU 24969 and (+/-)-8-hydroxy-2 (di-N-propylamino)tetralin hydrobromide (8-OH-DPAT)). The 5-HT depression of the hypoglossal discharge was prevented by applying a pretreatment with a specific 5 HT2 antagonist (ketanserin). Parallel to the hypoglossal discharge decrease, 5-HT elicited a permanent cervical root discharge along with a persistent inspiratory bursting. Adding the 5-HT precursor L-tryptophan to the bathing medium depressed the hypoglossal (XII) discharge without affecting the cervical one. 4. Local application of 5-HT within the hypoglossal motor nucleus decreased the hypoglossal output, revealing that the 5-HT depression of the hypoglossal discharge was at least partly mediated by the 5-HT effects at the level of the motoneurons. Local application of 5-HT within the cervical motor nucleus elicited a permanent firing in the cervical root with a persistent inspiratory bursting. 5. Intracellular analysis confirmed the existence of differences in central respiratory drive between cervical and hypoglossal motoneurons under control conditions, as well as differences in response to 5-HT. All the hypoglossal motoneurons became silent under 5-HT bathing, and showed no change in the input membrane resistance, a moderate depolarization, and a delayed central respiratory drive with a decreased amplitude. The cervical motoneurons became more active during inspiration, despite a decrease in the amplitude of the central respiratory drive, which was compensated for by a large depolarization and an increased input membrane resistance. Some cervical motoneurons even fired at a low rate during expiration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403828 TI - Respiratory-related activity of lower thoracic and upper lumbar sympathetic preganglionic neurones in the rat. AB - 1. The segmental distribution of cell bodies of sympathetic preganglionic neurones projecting into the left lumbar sympathetic chain beyond the L4 ganglion was determined in rats using retrograde transport of horseradish peroxidase. Labelled perikarya were found mainly in segments T13-L2 in the ipsilateral intermediolateral cell column. 2. Neurophysiological studies were conducted on this cell population in anaesthetized, vagotomized and artificially ventilated rats. 3. One hundred and thirty sympathetic preganglionic neurones were studied in spinal segments T13-L2, inclusive, after their antidromic identification following electrical stimulation of the left lumbar sympathetic chain between the 4th and 5th lumbar ganglia; sixty-six had on-going activity and thirty of the remainder were activated by the ionophoretic application of glutamate. Their axonal conduction velocities were 0.5-12.5 m/s which is in the B and C fibre range. 4. The discharge patterns of these sympathetic preganglionic neurones were analysed in relation to phrenic nerve discharge. Of forty-eight neurones analysed in this manner five had peak firing during inspiration (inspiratory related), five during early expiration (post-inspiratory related), four during expiration (expiratory related) with the remainder having a firing pattern unrelated to phrenic nerve discharge (non-modulated). 5. The ECG-related patterns of discharge of the same forty-eight neurones were analysed. Twenty-one had an ECG-related pattern of discharge. Glutamate-activated quiescent neurones and those with on going activity had a similar incidence of such modulation. Sympathetic preganglionic neurones with each type of respiratory modulation were found to have an ECG-related firing pattern. 6. The patterns of discharge of these neurones have been compared to those recorded, in previous studies, from sympathetic preganglionic neurones located at T2 which had axons projecting into the cervical sympathetic nerve and 'sympathoexcitatory' neurones of the rostral ventrolateral medulla. There appear to be some differences in the respiratory modulations of baroreceptor-sensitive neurones found within each of the three populations. Consequently, it is suggested that supraspinal pathways, other than those arising in the rostral ventrolateral medulla, may be important in influencing the activity of baroreceptor-sensitive sympathetic preganglionic neurones. PMID- 1403829 TI - Role of potassium in the reflex regulation of blood pressure during static exercise in man. AB - 1. The relationship between [K+] in venous effluent blood and alterations in mean arterial blood pressure was studied during static handgrip contractions at 15 and 30% of maximal voluntary contraction (MVC). 2. To further elucidate the importance of K+ in the reflex regulation of blood pressure a situation with normal recovery was compared with a situation in which 3 min of post-exercise occlusion was applied by arresting the circulation to the forearm just prior to the cessation of the contraction. 3. There was a temporal as well as quantitative correlation between venous [K+] and the blood pressure response during and after static exercise. During 30% MVC mean arterial blood pressure (MAP) attained 161.7 mmHg and venous [K+] 5.8 mM, while the corresponding values during 15% MVC were 121.5 mmHg and 5.0 mM. 4. In the occlusion period mean arterial blood pressure remained elevated above resting level and provided a measure of the magnitude of muscle chemoreflexes. In the same period venous [K+] was maintained at 5.3 mM and 4.6 mM following 30% MVC and 15% MVC respectively. This is indicative of interstitial concentrations of above 8-10 mM. This level is sufficiently high to stimulate type III and IV muscle afferents involved in the reflex regulation of blood pressure, and strengthens the notion that K+ may play an important role in eliciting the pressor reflex. 5. In contrast to [K+] the time course of venous blood concentrations of lactate and ammonia (NH3) exhibited a clear dissociation from the blood pressure recordings. PMID- 1403830 TI - Computer simulation of carbachol-driven rhythmic population oscillations in the CA3 region of the in vitro rat hippocampus. AB - 1. We used simulations of the in vitro CA3 region of the hippocampus to analyse the 5 Hz population oscillations recorded experimentally in carbachol. 2. A simulation model of the in vitro CA3 region was constructed with 1000 pyramidal neurones and 200 inhibitory neurones (100 producing fast inhibitory postsynaptic potentials (IPSPs) and 100 producing slow IPSPs of delayed onset). Each neurone contained nineteen soma-dendritic compartments. Pyramidal neurones contained six voltage- and/or calcium-dependent ionic currents, whose kinetics were consistent with voltage-clamp data. The connectivity and waveform of unitary synaptic events for excitatory and fast inhibitory synapses were consistent with dual intracellular recordings. This network was shown to generate previously described network oscillations, including synchronized bursts recorded in the presence of GABAA blockers, and synchronized synaptic potentials observed during partial blockade of GABAA inhibition. 3. The model generated 5 Hz oscillations as recorded in carbachol under the following conditions: (a) excitatory synaptic conductance was within a limited range; (b) there was blockade of fast and slow IPSPs (consistent with the experimental lack of effect of bicuculline and phaclofen on carbachol oscillations and the known depression of IPSPs by acetylcholine); (c) the after hyperpolarization (AHP) conductance was reduced (consistent with the known pharmacology of carbachol); (d) the apical dendrites of the pyramidal cells were depolarized, as suggested by the carbachol-induced depolarization of pyramidal neurones. Each oscillation was associated in pyramidal cells with a burst of action potentials riding on a depolarizing wave. The N-methyl-D-aspartate (NMDA) type of excitatory synapse was not necessary for the oscillations to occur. 4. Progressive reduction of excitatory synaptic strength led to an oscillation of the same frequency, with bursts riding on smaller EPSPs (consistent with the experiment). Further reduction of excitatory synaptic strength abolished the population oscillation by uncoupling the neurones. When excitatory synaptic conductance was too large, population oscillations were attenuated as the cells switched from a bursting mode to a repetitively firing mode. 5. Increasing the AHP conductance prolonged the interburst interval as expected. Inclusion of slow IPSPs exerted a similar effect. 6. When fast IPSPs were included, an oscillation with different characteristics emerged: a 10 Hz oscillation that was gated by compound GABAA IPSPs. On any oscillatory wave, few pyramidal neurones fired, and the firing of individual neurones was irregular.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1403831 TI - Cerebro-cerebellar projections from the ventral bank of the anterior ectosylvian sulcus in the cat. AB - 1. Stimulation of the ventral bank of the anterior ectosylvian sulcus (AESv) induced marked mossy fibre (MF) and climbing fibre (CF) responses in the cerebellar posterior vermis (lobules VI-VII) and moderate sized ones in the paraflocculus, paramedian lobules and crus I and II of the cat. The relay stations for these responses to the posterior vermis were investigated morphologically and electrophysiologically. 2. It can be considered that the MF responses were relayed at least in part via the dorsolateral, peduncular and paramedian pontine nuclei, since in these nuclei there were units orthodromically responsive to AESv stimulation and antidromically responsive to stimulation of the posterior vermis. The MF responses are thought to be relayed monosynaptically, since the distribution of axon terminals labelled after injection of wheatgerm agglutinin-conjugated peroxidase (WGA-HRP) into the AESv overlapped in these pontine nuclei with that of neurons labelled after injection of WGA-HRP into the posterior vermis. 3. It is thought that the CF responses are relayed in the caudomedial part of the medial accessory olive (MAOcm), because neurons in the MAOcm were orthodromically responsive to AESv stimulation and antidromically responsive to stimulation of the posterior vermis. 4. It is suggested that the cerebro-olivary projection which transmits the orthodromic responses in the MAOcm is indirect, via the superior colliculus (SC), because injection of WGA-HRP into the AESv labelled axon terminals not in the MAOcm but in the SC, and injection of WGA-HRP into the MAOcm gave rise to retrograde labelling of cells in the SC. Synaptic connections between the axon terminals of the cerebrotectal projection and the tecto-olivary neurons were demonstrated by extracellular unit studies in the SC. 5. The hypothesis that the CF responses were transmitted via the SC was supported by the finding that the CF responses disappeared transiently after muscimol or lidocaine was injected into the SC. 6. These findings provide evidence that the MF responses are transmitted at least in part via the cerebro-ponto-cerebellar projection, while the CF responses are relayed via the cerebro-tecto-olivo-cerebellar projection. These cerebro cerebellar pathways from the AESv are suggested to participate in conducting visual information to the posterior vermis. PMID- 1403832 TI - Presynaptic inhibitory effects of the peptides NPY, PYY and PP on nicotinic EPSPs in guinea-pig gastric myenteric neurones. AB - 1. Neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) affect gastrointestinal effector systems. Although their precise mode of action is unknown it is suggested that their effects are partly mediated by enteric neurones. Therefore, the aim of this study was to investigate the effects of NPY, PYY, avian PP (aPP) and bovine PP (bPP) on the electrophysiological behaviour of gastric myenteric neurones using intracellular recording methods. 2. In all thirty-one neurones tested, electrical stimulation of interganglionic fibre tracts evoked cholinergic, nicotinic fast excitatory postsynaptic potentials (fEPSPs). NPY, PYY and bPP (10-500 nM) inhibited the fEPSPs in a concentration dependent manner. Additionally, these peptides reversibly abolished spontaneously occurring nicotinic fEPSPs. None of the peptides exhibited any effect on the response to exogenously applied acetylcholine or on the postsynaptic excitability of the neurones. The inhibitory effects on the fEPSPs could not be reversed by perfusion of the alpha-adrenoceptor antagonist, phentolamine (1 microM). 3. In contrast, aPP had no significant effect on fEPSPs even when perfused at the high concentration of 1 microM. 4. The results suggest that NPY, PYY and bPP, but not aPP, act presynaptically to inhibit acetylcholine release from myenteric neurones of the gastric corpus, thereby suppressing fEPSPs. The study indicates a modulatory role for NPY, PYY and bPP in synaptic interactions within the enteric nervous system. PMID- 1403834 TI - Oral infections in the immunocompromised host. International Association for Dental Research Symposium 19 April 1991, Acapulco, Mexico. PMID- 1403833 TI - Intracoronary veratrine attenuates carotid baroreceptor reflex regulation of blood pressure in conscious dogs. AB - 1. The effect of activation of left ventricular cardiac receptors on carotid baroreflex control of blood pressure, heart rate, cardiac output, and total peripheral resistance was determined in conscious dogs. Previous studies in conscious subjects assessed only the effect on baroreflex control of heart rate. 2. Dogs with denervated aortic baroreceptors were equipped with aortic flow probes, cardiac pacing electrodes, and catheters in the aorta, vena cava, and left circumflex coronary artery. Both carotid sinus regions were prepared for reversible vascular isolation. 3. Left ventricular receptors were stimulated by an infusion of veratrine (0.1-1.0 micrograms kg-1 min-1) into the left circumflex coronary artery. 4. Veratrine infusion decreased control blood pressure only 10 +/- 2 mmHg, but it decreased the range of baroreflex control of blood pressure by 50% and decreased maximum baroreflex gain by 42%. Both the cardiac output and total peripheral resistance components of the baroreflex were attenuated. 5. Baroreflex control of blood pressure was unaffected by intravenous veratrine or by intracoronary infusion of vehicle. 6. Intracoronary veratrine had no effect after autonomic ganglionic blockade. 7. When cardiac output was kept nearly constant (by beta-adrenergic and cholinergic receptor blockade or by beta blockade and cardiac pacing), intracoronary veratrine still attenuated baroreflex control of blood pressure and total peripheral resistance. Veratrine impaired the ability of the baroreflex to utilize alpha-adrenergic mechanisms to control total peripheral resistance. 8. We conclude that activation of ventricular receptors attenuates baroreflex regulation of blood pressure in conscious dogs through an attenuation of baroreflex control of both cardiac output and total peripheral resistance. PMID- 1403835 TI - Changes in saliva of epileptic patients. AB - Unstimulated whole saliva samples of 27 indoor epileptic patients were studied on their protein composition using biochemical and immunochemical methods. A number of salivary proteins appeared at least partially to be hydrolyzed. In a number of saliva samples the concentration of carbohydrate-containing isoenzymes of amylase was reduced. In addition, the concentration of the 20 kD glycoprotein EP-GP was reduced by 60%. Sialic acid, the terminal sugar of the glycoproteins and mucins, was released for about 50% and in three salivas even nearly completely. Moreover, sialic acid- and fucose-containing epitopes could hardly be detected by monoclonal antibodies to human salivary mucins. As a consequence of this hydrolytic breakdown the saliva mediated aggregation of two S. sanguis strains had been reduced. In contrast, the aggregation of S. oralis had been maintained. PMID- 1403836 TI - Longitudinal study of parotid saliva in HIV-1 infection. AB - Parotid flow rate and chemistry of 78 HIV + gay/bisexual men and 27 HIV gay/bisexual controls were compared on a longitudinal basis at 4-month intervals over a 1 yr period for changes indicative of inflammatory or autoimmune diseases of the salivary glands, or reduced protective capacity toward oral opportunistic infection. Parotid saliva was examined for concentrations of sodium, chloride, phosphate, total protein, lysozyme, lactoferrin, secretory IgA, salivary peroxidase, histatin and albumin. Chloride, lysozyme and peroxidase were significantly higher in HIV + at all 3 examinations and increased in concentration over time. Although mean values for stimulated flow rate were not significantly different in the two groups over the year, there was a significant increase in the number of HIV + with reduced flow over time. In 6% of HIV + there was a marked reduction in flow rate and Sjogren's syndrome-like elevations in parotid chemistry but no enlargement. At all examinations low flow rate was significantly related to oral candidiasis; T4 levels were inversely related to oral candidiasis, but not to concentration of salivary components or flow rate; nor was AZT use. As a group the HIV + patients maintained normal flow rate and secreted normal or elevated concentrations of protective proteins. A subgroup, however, exhibited diminished flow over time and an increasing tendency to oral candidiasis and a diminution in output of histatins. PMID- 1403837 TI - Production of matrix metalloproteinase 2 (gelatinase/type IV collagenase) and 3 (stromelysin) by cultured oral squamous cell carcinoma. AB - Matrix metalloproteinases (MMPs) are believed to play an important role in tumor invasion and metastasis. MMPs have been identified as proforms of malignant tumor associated enzymes, such as procollagenase (proMMP-1) of M(r) = 53,000, progelatinase (proMMP-2) of M(r) = 72,000, proMMP-9 of M(r) = 92,000, and prostromelysin (proMMP-3) of M(r) = 59,000. Here we report that two cell lines of squamous cell carcinoma (SCC9 and SCC25) produce at least two matrix metalloproteinases (MMPs) in zymogen form, which have been identified as proMMP-2 and 3 by indirect immunofluorescence technique, immunoblot analysis, and gelatin substrate gel enzymography. Additionally, a 92-kDa gelatinolytic metalloproteinase (proMMP-9) was detected by gelatin-substrate gel enzymography. We propose that the ability of these tumor cells to secrete MMPs plays an important role in the malignant behavior of oral squamous cell carcinomas. PMID- 1403838 TI - Point mutations in the Ha-ras oncogene are detectable in formalin-fixed tissues of oral squamous cell carcinomas, but are infrequent in British cases. AB - Oncogene expression in human neoplasia has been examined extensively in the past decade. More recently the advent of the polymerase chain reaction (PCR) has facilitated studies of oncogenes and other DNA structures. Those few studies which have so far searched for oncogene changes in oral cancer have utilized frozen specimens. We report here an adaptation of the PCR technique applicable to DNA extracted from archival specimens. Our data complement recent findings that Ha-ras mutations are infrequent in oral squamous cell carcinomas among white caucasoid populations. PMID- 1403839 TI - Oral changes in interleukin-2 treated patients: a preliminary report. AB - Immunotherapy with high doses of interleukin-2 (IL-2) in patients with metastatic cancer is accompanied by multiorgan side effects. To determine the effect of this treatment on oral tissues, 5 cancer patients receiving a course of recombinant IL 2 (rIL-2) were followed. Oral pathology and subjective oral complaints were noted. Whole saliva parameters and routine blood and urine values were recorded daily before, during and after treatment. Mucositis and diminution of salivary flow occurred in all patients. Concomitantly, salivary sodium and protein were elevated. PMID- 1403840 TI - Experimentally induced ameloblastomas: a critical review. AB - This article reviews the experimental induction of ameloblastomas with emphasis on the acceptability of the induced tumors as being truly equivalent to ameloblastomas in humans. Attempts to induce odontogenic tumors in experimental animals have been made sporadically since the early 1960's but the yield of ameloblastomas has been low. Tumors resembling ameloblastomas, but not completely typical histologically and apparently lacking the invasive qualities of ameloblastoma, have been produced in mice using polyoma virus. However, the most typical ameloblastomas have been those induced in opossums, using ethylnitrosourea. Consequently, it is recommended that this model be used in any further attempts to produce ameloblastomas experimentally. PMID- 1403841 TI - Morphodifferentiation and histodifferentiation of the dental hard tissues in compound odontoma: a study of undemineralized material. AB - Dental hard tissues and mineralization at the enamel surface or in the ameloblastic epithelium were studied in 10 odontomas using undemineralized material. All the specimens showed a high degree of histo- and morphodifferentiation. Dentin formed the bulk of the tumors. Much of the enamel was prismatic and apparently normal and in almost every specimen were present enamel tufts and spindles. At greater magnification it could be seen that the prisms had a very irregular orientation. Cementum was mostly acellular. Calcified material formed focally in the intercellular portion of the enamel epithelium: this material showed a concentric layers arrangement. PMID- 1403842 TI - Acid production by Actinomyces viscosus of root surface caries and non-caries origin during glycogen synthesis and degradation at different pH levels. AB - Actinomyces viscosus strains, freshly isolated from root surface caries lesions and intact root surfaces, were studied for their glycogen synthetic and degradative activities at pH 4.5, 5.0, and 7.0 in a pH-stat. At all three pH levels, root caries origin of A. viscosus synthesized up to three times as much glycogen compared to non-root caries origin. Since root caries origin of A. viscosus strains initially synthesized large amounts of glycogen, a longer period of time was required to deplete this polymer, resulting in an extended period of acid production, even at pH 4.5 and pH 5.0. This study suggests that the ability of A. viscosus of root caries origin to synthesize large quantities of glycogen and subsequently degrade this stored polymer slowly with acid production, at acidic pH levels, may play an important role in the root caries process. PMID- 1403843 TI - Variants of the adenomatoid odontogenic tumor with a note on tumor origin. AB - Three rare variants of the adenomatoid odontogenic tumor (AOT) are described. A follicular AOT associated with an impacted and displaced 28, an extra-follicular variant mimicking a radicular cyst around the apex of 23 and a peripheral (epulis like) variant exhibiting a periodontal bone defect palatal to 21. On reappraisal of the origin and pathogenesis of the AOT, it would seem that this tumor or hamartomatous lesion is derived from odontogenic epithelium of the dental lamina complex or its remnants. PMID- 1403844 TI - Occurrence of oral leukoplakia and lichen planus in diabetes mellitus. AB - The occurrence of oral leukoplakia and lichen planus in 1600 patients with diabetes mellitus (815 type 1: insulin-dependent, 761 type 2: non-insulin dependent)-under care at the International Medicine Department-was studied. Precancerous lesions and conditions were diagnosed and grouped according to internationally accepted criteria. The prevalence of oral leukoplakia in diabetic patients was 6.2%, as compared to 2.2% in the healthy controls, that of oral lichen was 1.0% in the test-, and 0.0% in the control group. Leukoplakia and lichen both showed the highest occurrence in the second year of established diabetes, and their prevalence was higher among insulin-treated diabetics. Smokers were more often affected, by both kind of lesions, oral lichen showed a more frequent association with candidiasis. The prevalence of oral leukoplakia and lichen in diabetes mellitus patients was higher, than average ratios in population samples from the same country. PMID- 1403845 TI - Comparison between new saliva stimulants in patients with dry mouth: a placebo controlled double-blind crossover study. AB - Two new saliva stimulants: V6 and a mucin containing chewing gum were tested in this placebo-controlled double-blind crossover study. Forty-three patients (mean age 63 yr) complaining of dry mouth participated. The products were administered in a randomized order, and used for 2 wk each. The effect was evaluated by interviews and by determining changes in stimulated and unstimulated saliva flow rates. A positive effect was reported by 64%, 44%, and 26% of the patients using the mucin chewing gum, V6, and the placebo, respectively. More than 2/3 of the patients found the mucin chewing gum efficient at various times and situations. Sixty-one percent of the patients preferred the mucin chewing gum, 21% V6, and 5% the placebo product. Fifty percent of the patients had an increase in unstimulated salivary secretion rate from all products after 14 days regular use indicating a long-term effect. PMID- 1403846 TI - Purine modulation of prostaglandin F2 alpha (PGF2 alpha)-induced premature luteolysis in vivo in nonpregnant sheep. AB - In two separate experiments, control and PGF2 alpha-treated unilaterally ovariectomized ewes received vehicle or adenosine every four hours through an exteriorized catheter installed either to parafuse the ovarian vascular pedicle of the remaining ovary containing a corpus luteum (CL) or to infuse intrauterine ipsilateral to the remaining ovary with the CL. Infusions were given every four hours from day 7 through day 22 postestrus or until ewes returned to estrus. Chronic infusion of vehicle intrauterine or parafusion of the ovarian vascular pedicle with vehicle in PGF2 alpha-treated ewes shortened the interestrous interval compared to controls (P less than 0.05). However, chronic parafusion of the ovarian vascular pedicle with adenosine in PGF2 alpha-treated ewes prevented a PGF2 alpha-induced premature luteolysis (P less than 0.05) but not when adenosine was infused chronically intrauterine (P greater than 0.05). It is concluded that adenosine can block a PGF2 alpha-induced premature luteolysis in vivo and may have roles in regulation of luteal secretion of progesterone but it is probably not the embryonic antiluteolysin of early pregnancy in ewes. PMID- 1403847 TI - Inhibition of thrombin-induced platelet activation by dioctanoylglycerol pretreatment is not correlated with the 47 kDa protein phosphorylation. AB - The effect of platelet pretreatment with moderate amounts of 1,2 dioctanoylglycerol on subsequent thrombin-induced activation and its correlation with the degree of protein phosphorylation is studied. Protein kinase C preactivation (treatment with 1 microM dioctanoylglycerol for 20 min) significantly reduces thrombin-promoted platelet aggregation, cytosolic calcium rise, ATP-secretion and, albeit to a lesser extent, protein phosphorylation. Exposure of platelets to dioctanoylglycerol brings about a transient phosphorylation of a 47 kDa protein and a slight but more persistent phosphorylation of proteins of approximate molecular mass 26 and 68 kDa. It is hypothesized that the latter phosphoproteins are responsible for the inhibition of the thrombin-promoted platelet activation. Agonist-evoked aggregation is more affected by a long (20 min) rather than a short (1 min) pretreatment with dioctanoylglycerol, showing no correlation with the phosphorylation of the major substrates of protein kinase C. PMID- 1403848 TI - Comparison of second messenger formation in human keratinocytes following stimulation with epidermal growth factor and bradykinin. AB - We have examined the ability of recombinant human epidermal growth factor (EGF) and bradykinin (BK) to stimulate formation of inositol polyphosphates and sn-1,2 diacylglycerol (DAG), and mobilize intracellular Ca2+ ([Ca2+]i) in adult human keratinocytes (KC). Inositol polyphosphates were resolved by high performance liquid chromatography coupled with flow detector spectroscopy. Free intracellular calcium was quantitated using digital ratio imaging fluorescence microscopy of fura-2 loaded KC. The mass amount of DAG was quantitated using the DAG kinase reaction. When comparing maximal doses of BK (0.1 microM) and EGF (200 ng/ml), BK stimulated larger increases in all second messengers measured. The majority of cells responded rapidly to BK with global increases in [Ca2+]i. Cells responding to EGF were fewer in number and slower to respond with the Ca2+ signal being less pronounced. Treatment of cells with pertussis toxin (PTX) for 24 h significantly attenuated the BK-stimulated inositol polyphosphate formation and [Ca2+]i while the EGF response remained unaffected in both parameters. BK (10(-9) to 10(-6) M) did not stimulate DNA synthesis in KC as measured by [3H]-thymidine incorporation when cultures were treated for 5 days. These results demonstrate that the coupling and biochemical signals produced by stimulation of BK and EGF receptors in human KC are different and suggests that stimulation of second messenger formation from inositol lipid hydrolysis may not be an absolute requirement for the initiation of cell proliferation. PMID- 1403849 TI - Protein kinases associated with isolated mitotic spindles from mammalian cells: identification of a casein kinase II-like enzyme. AB - Mitotic spindles isolated from prometaphase-arrested mammalian cells contain associated protein kinases that are extracted by high salt treatment. Their fractionation by ion-exchange chromatography reveals three major peaks of protein kinase activity that phosphorylate brain microtubule-associated proteins and differ in their substrate specificity. One of them has been identified as a casein kinaseII-like enzyme. A mitotic spindle-associated 325 kDa protein related to brain MAP1B is a major substrate for this casein kinase II-like enzyme. Another mitotic spindle protein kinase has been tentatively identified as a proline-directed protein kinase. PMID- 1403850 TI - Protein kinase C phosphorylates both serine and threonine residues of the mRNA cap binding protein eIF-4E. AB - Several lines of evidence indicate that phosphorylation of the 25 kDa mRNA cap binding protein (eIF-4E) stimulates the efficiency of translational initiation. While the protein kinases which catalyze this reaction in intact cells have not been completely identified, evidence suggests that protein kinase C phosphorylates serine residues of eIF-4E in intact cells. In this study we demonstrate that protein kinase C also phosphorylates threonine residues of recombinant human eIF-4E in vitro. Phosphorylation of threonine and serine was observed over a range of eIF-4E and salt concentrations. However, relatively low levels of phosphorylation were seen even under optimal conditions. Similar results were observed with native eIF-4E purified from human erythrocytes. These findings demonstrate that protein kinase C can phosphorylate both serine and threonine residues of eIF-4E in vitro, but suggest that protein kinase C may not be the primary enzyme that phosphorylates eIF-4E in vivo. PMID- 1403851 TI - Prosthetic management of dysphagia after a stroke--an unusual combination of problems: a clinical report. PMID- 1403852 TI - Rehabilitation with calvarial bone grafts and osseointegrated implants after partial maxillary resection: a clinical report. AB - Osseointegrated implants can be positioned on the nondefect side of a midline maxillary resection if there is sufficient residual bone. Axial loading of the implants is difficult because the axis of rotation for an obturator prosthesis is located along the palatal margin of the defect. Rotation of the prosthesis due to a class I lever will encourage stresses within the implants and the bone surrounding the implants on the nondefect side, and this may be detrimental. Placement of implants within the defect will prevent rotation of the prosthesis and encourage axial loading of the implants. PMID- 1403853 TI - Simplified fabrication of the interim denture using a vacuum-forming machine: a clinical report. PMID- 1403854 TI - Twelve-year clinical report on multiple endodontic implant stabilizers. PMID- 1403855 TI - Fracture resistance of composite and amalgam cores retained by pins coated with new adhesive resins. AB - This study determined the effects of coating pins with either Panavia EX or with 4-META (Cover-Up) materials on the fracture resistance of pin-retained amalgam and composite cores. Gold-plated stainless steel (TMS) and titanium (Filpin) self threading pins were used. Findings of this study corroborated the findings of several other studies that the use of pins reduces the fracture resistance of restorations. However, coating the pins with adhesion promoters such as Panavia EX and 4-META materials has been found to be effective in improving the fracture resistance. Cross-preference was observed between TMS and Filpin pins; that is, Panavia material coating was more effective with TMS pins, while 4-META was more effective with Filpin pins. PMID- 1403856 TI - Clinical management of abutments with intracoronal attachments. AB - A method of preparing teeth to accommodate intracoronal attachments is presented. The resulting prosthesis incorporates a fixed partial denture with physiologically contoured crowns and a removable partial denture with a precisely determined path of insertion. These techniques stress the importance of surveyed diagnostic casts and coordinated tooth preparations for artificial crowns to facilitate treating complex cases. PMID- 1403857 TI - Effect of dentinal bonded resin post-core preparations on resistance to vertical root fracture. AB - An in vitro study was conducted to compare the resistance to failure of two restorative protocols for endodontically treated teeth. Half of 24 specimens received cemented cast post-core restorations and the other half were restored with dentin-bonded composite resin using the ferric oxalate, NTG-GMA, and the PMDM system developed by Bowen. The dentin-bonded resin post-core restorations provided significantly less resistance to failure than the cemented custom cast post-core. The dentin-bonded resin post-core fractured in every instance before the root fractured. A greater force was required to cause failure of the resin post as the cross-sectional area of the post increased. PMID- 1403858 TI - A comparative study of ceramic crown margins constructed using different techniques. AB - This study compares three variations of the direct lift-off technique utilizing porcelain materials with thermoplastic, modeling liquid, and visible light-cured resin carriers. Three commercially available materials were evaluated. Vita, Ducera, and Dentsply Spectrum. Measurements were made of the width of the marginal gap for three sites at each of four stages: (1) after the shoulder firing, (2) after the body-incisal firing, (3) after the glaze firing, and (4) after a correction firing. All techniques produced marginal gaps in the clinically acceptable range. Use of the Vita thermoplastic carrier porcelain material resulted in the smallest marginal gap at all but the body-incisal stage. Crowns done with the Ducera and Spectrum materials had statistically similar marginal gaps at all but the glaze stage, where the Ducera material crowns demonstrated the largest marginal gaps. PMID- 1403859 TI - Composite resin color change after vital tooth bleaching. AB - Color change of composite resin was determined with the Minolta Chroma meter (CR 100) after four sessions of vital bleaching. Specimens of selected composite resin materials were subjected to vital bleaching (37% H3PO4/1 minute, then 30% H2O2/infrared light/30 minutes.) Specimens were stored in water between bleaching. Control specimens were used to determine the effects of water storage alone. Initial L*a*b* color readings were made on 24-hour hydrated specimens. Final L*a*b* readings were made on 24-hour hydrated specimens. Calculations were made for the delta E values for each specimen. Mean delta E values and standard deviations were obtained for each material. Two-way ANOVA and Newman-Keuls analyses showed significant (alpha = 0.05) color change for most bleached materials. Additionally, some materials had delta E values greater than 3. These were visibly lighter compared to their controls. Vital bleaching produced color change in most composites as measured with the Chroma meter. This technique may be used to lighten dark-colored or stained composite resin restorations. PMID- 1403860 TI - Effects of cement, cement space, marginal design, seating aid materials, and seating force on crown cementation. AB - An evaluation of the effects of a die spacer, the seating force, the marginal design, seating aid materials, and the cement type during cementation was conducted. Two stainless steel dies were used: one with a 1 mm shoulder and the other with a shoulder and a 65-degree bevel. Ten stone dies were produced from each metal die and half were painted with four layers of die spacer. The crowns were waxed on the dies and cast in a nonprecious alloy, and the seating of crowns was measured with a micrometer before and after cementation. Comparisons were made between zinc phosphate and glass ionomer cements under two seating forces of 5 and 30 lb using an orangewood stick or E-Z-bite seating aid. ANOVA and the Newman-Keuls test revealed that the use of a die spacer, a heavier force of 30 lb, and glass ionomer cement significantly improved crown seating. The beveled preparation led to superior crown seating when the heavier force or glass ionomer cement was used. The orangewood stick and bite device had a similar effect on crown seating. PMID- 1403861 TI - Effects of 'resin-compatible' cavity varnishes on composite resin microhardness. AB - Although the use of cavity varnishes with composite resins has traditionally been discouraged, several "resin-compatible" varnishes are currently available. This in vitro study evaluated the effects of resin-compatible cavity varnishes on a hybrid composite resin. The results of the study indicate that these varnishes soften the composite resin in contact with varnished dentin. PMID- 1403862 TI - Viscosity of monophase addition silicones as a function of shear rate. AB - The viscosity of monophase addition silicone impression materials was measured as a function of shear rate. The setting of mixed catalyst and base was prevented by addition of a small amount of phenyl propiolic acid. All products showed a 6- to 10-fold decrease in viscosity with an increasing shear rate (shear thinning). The addition of phenyl propiolic acid had little or no effect on the viscosity of three materials. However, when added to the catalyst or base only of two products, it increased their viscosity and exaggerated the shear thinning effect. PMID- 1403863 TI - A secondary lingual casting for removable partial dentures. AB - This article describes a technique for constructing a nickel chromium alloy lingual casting that reinforces a removable partial denture against heavy anterior occlusion. The metal can be cast into a thin secondary casting, and it is easily etched and bonded to the resin anterior teeth and associated base. This type of lingual casting has the potential to provide a simple and effective solution to the problem of repeated fracture or displacement of anterior teeth in many restorations. PMID- 1403864 TI - Mandibular complete denture impressions with fluid wax or polysulfide rubber: a comparative study. AB - Some authors have stated that wax cannot be used to make impressions for complete dentures, while others have found that wax has some advantages over elastomeric impression materials. The purpose of this study was to compare mandibular impressions made with a fluid wax to those made with light-body polysulfide rubber. Fifteen maxillary and mandibular complete dentures were made using fluid wax as a final impression material. For comparison, 15 maxillary and mandibular complete dentures were made using light-body polysulfide rubber. The number of adjustments required over 1 year was recorded. No statistical difference in adjustments was noted between the two groups. PMID- 1403865 TI - The position of the neutral zone in relation to the alveolar ridge. AB - Included in this study are 21 edentulous patients. They were classified according to their period of edentulousness into two groups. One group was edentulous from 1/2 to 2 years. The other group was edentulous for more than 2 years. The neutral zone (NZ) was located for each patient by using record bases, and an impression compound as the occlusion rim. A 30-gauge stainless steel wire was adapted along the center of the alveolar ridge on the final cast. A 24-gauge stainless steel wire was adapted and stabilized over the center of each occlusion rim. An occlusal view radiograph was obtained of each recording base and its cast. Each film was placed in a viewing box and the relationship between the images of the two wires in the buccolingual direction was studied in the anterior, premolar, and molar regions on the left and right sides. Where the two images coincided a zero score was given. In the case of buccal location a plus scores was given, and where there was a lingual location of the (NZ), a minus score was given. All measures were taken in millimeters. Statistical analysis was performed between the two groups. The longer the period of edentulousness, the more buccally/lingually located was the NZ. PMID- 1403866 TI - Denture tooth selection: an analysis of the natural maxillary central incisor compared to the length and width of the face: Part II. AB - This is the second part of a project conducted by the Removable Prosthodontic Faculty to compare the length and width of the maxillary central incisor with the length and width of the face. In this article, gender of the students was the main consideration. Three hundred fifty men and 138 women students participated in the project. PMID- 1403867 TI - Laboratory wear investigation of resin posterior denture teeth. AB - This investigation compared the wear resistance of three "improved" resin posterior denture tooth formulations with two conventional products on a mechanical toothbrush abrasion machine. The ability of the teeth to resist this type of abrasion was evaluated by determination of the weight loss during 339 hours of brushing with firm nylon bristle toothbrushes. All brands exhibited negligible loss, with the conventional brands performing better than the "improved" formulations. PMID- 1403868 TI - Effect of repair surface design, repair material, and processing method on the transverse strength of repaired acrylic denture resin. AB - The transverse strengths of blocks of denture base acrylic resin repaired with autopolymerizing monomer and polymer and autopolymerizing monomer and heat-cured polymer were measured with a three-point bending test. Three repair joints were studied: butt, round, and 45-degree bevel. Three processing methods were used: bench cure, hydroflask with hot water for 10 minutes, and hydroflask with hot water for 30 minutes. The strengths of repairs made with round and 45-degree bevel joint designs were similar and significantly greater than those with a butt joint design. The strengths of repairs processed in a hydroflask for 10 minutes and 30 minutes were similar and significantly greater than those cured on the bench top. There was no difference in the strength of repairs made with autopolymerizing monomer and polymer and autopolymerizing monomer and heat-cured polymer. PMID- 1403869 TI - The knife-edge tendency in mandibular residual ridges in women. AB - To investigate the bone resorption pattern of the residual alveolar bone, the morphologic change that occurred in mandibles was analyzed with standardized lateral cephalographs of 30 edentulous patients (15 women and 15 men). The longitudinal morphologic changes were measured at the sagittal sections of the mandibular bony contour at the symphysis area on superimposed cephalographic tracings. To quantify the morphologic change, a knife-edge index (KEI) was developed as the area change divided by the height change. Geometrically, the higher value of KEI represents the greater tendency to become a narrow residual ridge. The KEI values were statistically higher in the women than in the men (p less than 0.002). In addition, the value of KEI seems to correlate with osteopenic change at the center point of the body of the second vertebra (p less than 0.01). The continuous bone resorption activity in the edentulous mandible of women seems to be emphasized at the labial and lingual surfaces of the residual alveolar bone, resulting in a knife-edge type of residual ridge. PMID- 1403870 TI - An analysis of the effect of mandibular length on residual ridge loss in the edentulous patient. AB - The relationship of mandibular length to residual ridge loss was studied in 22 edentulous patients. Tracings made from cephalometric films taken at initial insertion of complete dentures and at 20 years after placement were measured. Mandibular length was determined to have no statistical relationship to the reduction in residual ridge height in either the maxillae or the mandible. In addition, alveolar bone loss in the one jaw had no relationship to the amount of loss in the other jaw. PMID- 1403871 TI - A surgical guide for implant placement. AB - Mounted diagnostic casts aid in determining whether sufficient space exists for a fixed cantilevered implant prosthesis. These casts are also used to construct a surgical guide. Such a technique is described. PMID- 1403872 TI - An appliance to correct mandibular deviation in a dentulous patient with a discontinuity defect. AB - The mandibular discontinuity defect is one of the most difficult problems in prosthetic dentistry. This article describes an appliance that has been used successfully in reducing or correcting the deviation in dentate patients who have experienced mandibular resection. It consists of a prefabricated integrated tube and plunger that are hinged to clear acrylic resin maxillary and mandibular appliances. PMID- 1403873 TI - Occlusal force after partial mandibular resection. AB - Surgical resection of a segment or loss of mandibular continuity can adversely affect most of the structures essential for maximum occlusal force. Five subjects who had partial mandibular resections for treatment of squamous cell carcinoma were studied. Occlusal force was recorded before and after cancer treatment and following prosthetic rehabilitation. A gnathodynamometer was used to record anterior occlusal force. Five edentulous and five dentate cancer-free subjects matched for age were studied to establish comparable normative data. The null hypothesis that partial mandibular resection would not affect maximum occlusal force was rejected (p = 0.0101). Mandibular resection did alter maximum occlusal force. The impact of the decrease in maximum occlusal force on masticatory function is yet to be determined. PMID- 1403874 TI - Tenderness on palpation and occlusal abnormalities in temporomandibular dysfunction. AB - Tenderness on palpation indicates objective painful symptoms. This study investigated the tenderness of the temporomandibular joint, muscles and their relation to occlusion in patients with temporomandibular dysfunction. Two hundred ten patients were examined; 96% had tenderness and 80% of cases of tenderness were diagnosed as occlusally related. The average number of tender areas was 5.4 per patient, despite the contribution of occlusion. Tenderness was observed most frequently in the lateral pterygoid muscle, followed by the insertion of temporal muscle. There was no correlation of temporomandibular joint tenderness to muscle tenderness, while tenderness of certain muscles to each other was correlated. Differences were related to the state of occlusion in the number of tender areas, to the ratio to tenderness of elevator muscles to horizontally acting muscles, and to the frequency of unilateral tenderness. The association of muscle tenderness and occlusion was suggested. PMID- 1403875 TI - The effect of age on condylar asymmetry in patients with craniomandibular disorders of arthrogenous origin. AB - A group of patients with a craniomandibular disorder of arthrogenous origin demonstrated an age-related variation of condylar asymmetry with age. This may reflect a greater depletion of the mesenchymal cell layer, which is responsible for adaptation of the articular surface as age increases. This would then result in greater deterioration of the articular surfaces and a consequent decrease in condylar asymmetry. PMID- 1403876 TI - Wet versus dry enamel ablation by Er:YAG laser. AB - The purpose of this study was to observe tooth structure and pulpal temperature changes in extracted human teeth subjected to a pulsed Er:YAG (2.94 microns) laser. Two teeth were irradiated while dry and three teeth while moistened by a fine water mist. When the dry teeth were irradiated, there was minimal enamel ablation. SEM of the resulting surface showed rounded fragments of enamel rods, enamel melting, cracks, and smooth-edged voids. Intrapulpal temperature measured by thermal sensor rose more than 27 degrees C. When the laser application on the teeth was pulsed with a constant fine water mist, enamel and dentin were efficiently ablated. SEM of the resulting surfaces showed fissures and conical craters with sharp enamel projections remaining. Intrapulpal temperatures rose an average of 4 degrees C. These results indicate that pulsed Er:YAG (2.94 microns) used with a water mist removes enamel and dentin without producing significant pulpal temperature changes. PMID- 1403877 TI - A scanning electron microscopy study of the effect of bleaching agents on enamel: a preliminary report. AB - The effect of bleaching agents on the enamel surface was examined by scanning electron microscopy. The comparison of treated to untreated enamel revealed that the treated surface had increased surface change and porosity after the equivalent of 30 hours of exposure to the bleaching agent. The degree of alteration of enamel surface was not uniform and was influenced by cleanliness (oral hygiene) of the treated teeth and apparent variation in calcification. The enamel surface developed varying degrees of surface porosity and alteration. PMID- 1403878 TI - Effects of temporary cementation on permanent cement retention to composite resin cores. AB - This in vitro study compared the effects on retention of base metal cylindrical retainers placed on composite resin cores when pretreated with eugenol and noneugenol temporary cements. Sixty composite cores and base metal cylindrical retainers were tested. The cores were pretreated with eugenol and noneugenol temporary cements before eventual cementation with resin and zinc phosphate cements. Cemented core retention was measured by application of a compressive force to the cores in an Instron machine. Differences were found between the two permanent cements. Pretreatment with eugenol cement reduced retainer retention with resin cements, but had no effect with zinc phosphate cement. Pretreatment with noneugenol cement did not reduce retainer retention. PMID- 1403879 TI - A review of the strength properties of dental ceramics. AB - New ceramic materials for restorative dentistry have been developed and introduced in recent years. This article reviews advantages and disadvantages of dental ceramics, concentrating on strength properties. Included are factors affecting the strength of dental ceramic materials and the most common mechanisms for increasing the strength of dental ceramics. The properties of presently available materials such as dispersion-strengthened ceramics, cast ceramics, and foil-reinforced materials are discussed. Current research efforts to improve the fracture resistance of ceramic restorative materials are reviewed. A description of methods to evaluate the strength of ceramics is included, as a caution concerning the interpretation of strength data reported in the literature. PMID- 1403880 TI - Long-term outcomes for remedial students. AB - A recent survey of dental schools concluded that current efforts toward remediation are inadequate. A remedial waxing course providing recognition training before production attempts, emphasis on formative self- and peer evaluation of projects, and application of a highly structured format for ensuring relevant practice had been developed and favorably evaluated previously. The current report follows the progress of two differently trained remedial groups and the remainder of the class in two courses following remediation. On the five subsequent practical examinations analyzed, the experimental group continued to perform at the class mean. On one practical examination, the experimental group significantly outperformed the traditional group (p less than 0.02). For three of the five examinations, the traditional group was significantly outperformed by the class. One of the six students in the experimental group required additional remediation. Of the seven in the traditionally remediated group, one left school and four required additional remediation. An apparent changing remediation pattern in the preclinical training period is described and possible reasons for the change are explored. PMID- 1403881 TI - A simplified intraoral surveying device. AB - This article describes an easily made and used intraoral surveying device that can aid the dentist in transferring needed preparation information from the diagnostic cast. This device also allows checking of the preparations as they are progressing. The device consists of a Proxabrush handle and a drafting lead. PMID- 1403882 TI - Accuracy and dimensional stability of a combined hydrocolloid impression system. AB - The accuracy of a combined hydrocolloid impression system was studied as a function of time of pour. There was little change in dimension between posts for all time intervals studied. No statistically significant differences were noted among the observation periods until 3 hours. The results indicate that for the impression system studied, a 3-hour pouring time can be used for transport to a commercial dental laboratory, provided the impressions are stored in 100% relative humidity. The hydrocolloid impression system tested resulted in a stone cast of slightly deviating dimensions compared with the master model. Therefore laboratory procedures should compensate for cement thickness, taking into account the minimal changes in dimensions of the die. PMID- 1403883 TI - The dimensional accuracy of rectangular acrylic resin specimens cured by three denture base processing methods. AB - The dimensional accuracy of rectangular acrylic resin specimens was examined when they were processed by three methods: a conventional method, the SR-Ivocap system, and a microwave curing method. The dimensional accuracy was evaluated by the change of the distance vector V, which is calculated by means of measurements of the distances between fixed points on specimens. The specimen cured by the SR Ivocap system exhibited less dimensional change (p less than 0.05) than those cured by the conventional and the microwave curing methods. The SR-Ivocap system might produce a more accurate denture base than the conventional and the microwave curing methods. PMID- 1403885 TI - Equipping a dental laboratory: fabricating a pressure pot. AB - A pressure pot has many applications in dentistry. This article describes a simple method of converting an everyday kitchen pressure cooker into one that can be used in dentistry. The technique is simple, and the components needed are readily available at a local hardware or department store. The advantage of this pressure pot is that it can be made for one third to one half the cost of purchasing one from a manufacturer. PMID- 1403884 TI - Microwave processing of cleft palate orthopedic expansion devices. AB - This article describes a method for making a palatal expansion device for use in conjunction with orthopedic repositioning of the premaxilla in patients with bilateral cleft palate. The technique of constructing the devices involves the microwave processing of a permanent soft liner and a heat-cured acrylic resin in a single-stage curing cycle. The resultant expansion device has the advantages of a soft liner for retention in the nasal cavity and an oral cavity surface that is smooth and closely adapted to the tissues. A paper cover is used during the flasking process, which allows packing of materials without displacement into undesirable locations. PMID- 1403886 TI - Improved acrylic resin provisional restorations. PMID- 1403887 TI - Simplifying the altered cast impression technique for distal-extension removable partial dentures. AB - This technique allows construction of a detachable custom tray by the dental laboratory before the distal extension RPD framework is returned to the dentist. This permits a framework try-in with unencumbered physiologic relief, rapid attachment of the custom tray, subsequent impression making, and possibly jaw relation records all in one patient visit. PMID- 1403888 TI - An alternative immediate complete denture impression technique. AB - An alternative immediate denture impression technique for extremely mobile teeth, utilizing amalgam condensers, has been presented. The apically applied pressure on the mobile teeth minimizes the risk of accidental tooth extraction during impression removal. PMID- 1403889 TI - A simple method for permanent identification of dentures. PMID- 1403890 TI - Simulation of lateral pressures to identify possible occlusal interference during sleep. PMID- 1403891 TI - Calculus and plaque removal from osseointegrated implant titanium abutments. PMID- 1403892 TI - Insertion adjustment of denture base surface contacting the mylohyoid ridge. PMID- 1403893 TI - Technique to diminish discomfort from the palatal injection. AB - A new technique for diminishing the discomfort of a palatal injection has been described. The technique utilizes a cotton pellet saturated with dichlorodifluoromethane spray held in contact with the tissue 5 seconds to freeze a small portion of the surface tissue. The injection needle then penetrates the frozen tissue with little discomfort to the patient. PMID- 1403894 TI - Evulsion of a percutaneous implant abutment: a clinical report. PMID- 1403895 TI - Alloplastic cranial implants made from computed tomographic scan-generated casts. AB - The complexity of cranioplasty increases with increased defect size. It is difficult to produce a symmetric, accurate implant presurgically or at the time of surgery when the defect is greater than 50 cm2. The procedure is also more difficult to perform when the defect is located in the temporal, infratemporal, or frontal areas. A new procedure generates a three-dimensional cast of the skull through computed tomography and computer-aided design reformation. This article describes the process of model generation and the production of a preprocessed cranial implant. To date, six cranial implants have been made with this technique. The whole head models are accurate and help the neurosurgeon prosthodontist team in the creation of a symmetric, anatomically correct restoration. It is the technique of choice for large implants or where the cranial bones are thin. It is not necessary to augment or alter the implant during surgery. The technique reduces surgical time, and postsurgical complications have been minimal. PMID- 1403896 TI - Sleep apnea prosthesis for dentate patients. AB - This article describes clinical and laboratory techniques for the fabrication of a sleep apnea prosthesis for a dentate patient. The treatment objective is to posture the mandible at an increased vertical and protrusive position to diminish or eliminate the collapse of the base of tongue into the oropharynx. During fabrication of the prosthesis, cephalograms are used to evaluate spatial change between the base of the tongue and the posterior pharyngeal wall. PMID- 1403897 TI - The design of a two-part acid-etched resin-bonded fixed partial denture. AB - A new framework design is presented for resin-bonded, acid-etched, fixed partial dentures. This innovative design divided the restoration into two parts, each with a separate path of insertion. The preparation of abutment teeth required minimal reduction and the pontic could not be displaced during function. Thirty five patients with missing posterior teeth have been treated with this imaginative approach and after approximately 2 years, there have been no debonding failures. PMID- 1403898 TI - Clinical evaluation of the gingiva around single-crystal sapphire endosseous implant after experimental ligature-induced plaque accumulation in monkeys. AB - This study was performed to evaluate clinical changes of the gingiva with plaque accumulation around the single-crystal sapphire implant. Four implants were inserted into mandibular and maxillary edentulous regions, and the superstructure was inserted 1 month after insertion of the implants in each of nine monkeys. Plaque control was maintained for 3 months after insertion to set up the baseline. Plaque was allowed to accumulate on one side by placing the ligature around the implant and natural teeth without any plaque control, and on the other side plaque control was continued for 9 months. Both the implant and natural teeth on the ligature side showed a significant increase in the clinical parameters of plaque index, gingival index, and probing depth. No significant difference was obtained between the implant and natural teeth. These findings indicate that plaque control is of great importance for maintaining the health of peri-implant gingiva. PMID- 1403899 TI - Radiotherapeutic management of an orocutaneous defect with a balloon-retaining stent. AB - Maxillary resection defects have traditionally been technically difficult to treat with conventional radiation therapy. The irregular contours of the defect lead to an uneven distribution of the radiation doses. The potential to undertreat defects of microscopic involvement may leave residual disease. Tissue morbidity is high at isolated "hot spots" or at locations of excessive dose distribution. The use of a water-filled balloon bolus in conjunction with a balloon-retaining stent can significantly improve treatment efficacy and decrease tissue morbidity. This article describes a technique for the fabrication of a balloon-retaining stent for an orocutaneous defect. PMID- 1403900 TI - Lip stent for positive pressure in keloid treatment. AB - The fabrication of a device to exert pressure on a keloid of the lip is described. In addition to providing uniform and adjustable compression, it is strong enough to resist distortion. It is also lightweight, easy to insert and remove, comfortable to wear, esthetically pleasing, easy to clean and fabricate, and inexpensive. The prosthesis is a two-component device made from clear acrylic resin assembled with a spring and screw. The stent should remain in place 12 hours a day for 6 to 12 months. PMID- 1403901 TI - A shade guide for acrylic resin facial prostheses. AB - The value and success of a well-fitting and anatomically correct prosthesis are compromised if the color does not match the adjoining tissue. Color and color science are reviewed to help develop a simplified acrylic resin shade guide to aid in fabricating acrylic resin facial prostheses. This guide will help the clinician obtain a good intrinsic shade and minimize extrinsic coloration. PMID- 1403902 TI - The effect of a deprogrammer on the position of the terminal transverse horizontal axis of the mandible. AB - This study measured the amount of positional change in the terminal transverse horizontal axis of the mandible that results from altering undesirable neuromuscular influence. Centric relation records were made on 19 healthy subjects before and after deprogramming. The axis was located with a computerized axiograph, and the centric relation records were compared in vivo at the axis location. The positional change of the axis was quantified in three dimensions at an accuracy of +/- 0.05 mm. The net amount of positional change was compared to scores from the temporomandibular joint scale to test for correlation with the potential for developing a temporomandibular disorder. The findings showed that the amount of positional change in the terminal transverse horizontal axis in 18 of 19 healthy patients after 12 hours of deprogramming was less than 0.5 mm and did not correlate with scores from the TMJ Scale. PMID- 1403903 TI - Effects of posterior teeth replacement on temporomandibular joint sounds: a preliminary report. AB - Previous reports have shown the prevalence of jaw clicking to be significantly higher in a population with missing posterior teeth compared with an dentulous population. This study presents a 2- to 5-year assessment of the effects of posterior teeth replacement on the amplitude of jaw clicking in subjects who were asymptomatic in all respects except jaw clicking. Patients requiring removable partial dentures (RPDs) were clinically and anamnestically examined and temporomandibular joint (TMJ) sounds were recorded using a modified stethoscope attached to an adjustable headgear. Amplified signals were displayed on a strip chart recorder. The amplitude of TMJ sounds at preinsertion of RPDs were 27.5 +/- 17.7 dB at opening, and 11.1 +/- 12.7 dB at closing. Similar values after prosthesis insertion were 15.8 +/- 17.0 dB and 7.4 +/- 7.5 dB, respectively. Paired t test analyses showed significant differences in the amplitude of sound for opening and closing before inserting the prosthesis (p = 0.003) and for opening before and after treatment (p = 0.014). Following replacement of posterior teeth, the clicking amplitude decreased in 68% of recordings, remained unchanged in 11%, and increased in 21%. PMID- 1403904 TI - Report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry. AB - The committee screened several hundred articles, citing 518 published papers. Some are present quality in research, others provide clinical interest, and some are identified as misleading. New techniques in pulp physiology and pathology are reported. Laser use and techniques in prevention, restorative dentistry, and materials use are reported. Epidemiology of selected diseases and the results of various formulations for treatment are cited. Diagnosis of craniomandibular dysfunction is well represented as well as references to literature reviews and other sophisticated scientific investigation. Research on adhesives is presented in respect to bonding agents for dentin and enamel. Several clinical studies are included, along with customary laboratory reports on several materials. PMID- 1403905 TI - Resin-bonded cast coverage for fractured posterior teeth. AB - Enamel-dentin fracture without pulpal involvement of intact posterior teeth demands restoration of form and function while preserving as much sound tooth material as possible. A partial-coverage restoration cast in nonprecious metal and air-abraded and bonded to the tooth by an adhesive resin is suggested. The strong bond of the adhesive resin to the enamel and dentin of the tooth and to the air-abraded metal allows for simple fabrication of a cast partial coverage that requires only minimal tooth preparation. PMID- 1403906 TI - Effect of tray space on the accuracy of monophasic polyvinylsiloxane impressions. AB - The effect of tray space on the dimensional accuracy and stability of impressions made from four brands of monophasic polyvinyl siloxane material was assessed on the recovered stone casts by quantitative and qualitative methods. In general, both evaluation methods agreed that tray space and repeat pour did not affect the accuracy of the dies for individual castings. But disagreement was observed in the findings for fixed partial dentures (FPDs). Quantitative measurement of the interpreparation (IP) dimensions did suggest the possibility of a potential problem when a FPD is cast in one piece because of a significantly reduced distance between the two abutments. However, from the findings of this study it can be concluded that a rigid stock tray can be used with a monophasic polyvinyl siloxane impression material. PMID- 1403907 TI - The effect of disinfection procedures on flexural properties of denture base acrylic resins. AB - This study evaluates the effects of long-term disinfection immersion on the flexural properties of denture base resins; it was conducted against a background of increasing awareness of the importance of cross-infection control in dental clinics and laboratories. The transverse bend testing procedure used followed that specified in the International Standard for denture base polymers. The results demonstrate that alcohol-based disinfectants are not suitable for use with denture base materials of non-cross-linked acrylic resin. PMID- 1403908 TI - Linear dimensional variability of three denture base resins after processing and in water storage. AB - It has been shown that denture base resins shrink during curing and expand during storage in water. This investigation measured and compared linear dimensional changes of three denture base resins that occurred during processing and after storage in water for 30, 60, and 90 days. Triad, Accelar 20, and Lucitone 199 long- and short-cured resins were studied, and it was found that Accelar 20 resin exhibited the least curing shrinkage and Lucitone 199 resin short-cured exhibited the most. However, no significant differences occurred between the groups. After 90 days of water storage, the only resin that exhibited a shrinkage from the processed state was Accelar 20. All of the expansion or shrinkage changes were so small that they were not statistically significant and should not be clinically detectable. PMID- 1403909 TI - A vinyl polysiloxane die used to make interim restorations. AB - A die made of vinyl polysiloxane is a great aid for making interim restorations and for establishing correct gingival contours for finer restorations. This article describes the rationale and procedures for such a procedure. PMID- 1403910 TI - Composite resin layering: an esthetic technique for restoring fractured anterior teeth. PMID- 1403911 TI - Development of radiopaque acrylic resins for prostheses. PMID- 1403912 TI - Stresses at the dentinoenamel junction of human teeth--a finite element investigation. PMID- 1403913 TI - Pattern of tooth contacts in eccentric mandibular position in young adults. PMID- 1403914 TI - Effect of glass ionomer liners on bonding strength of laminate veneers. AB - This study compared shear bond strengths of porcelain laminate veneers, fabricated on refractory dies, which were lengthened incisally by 0.5 mm. Specimens were divided into four separate groups. In group A, the teeth were reduced 0.5 mm and the bonding was to enamel. The teeth of the remaining groups were reduced 1.0 mm and the bonding was to dentin. For two of the groups glass ionomer liners were applied before etching. Bonding to enamel was best, with cohesive fractures in porcelain. In the other groups, failure was adhesive in nature, occurring at the resin-tooth interface. PMID- 1403915 TI - Apparent intrusion of natural teeth under an implant-supported prosthesis: a clinical report. PMID- 1403916 TI - Comparison of the fracture strengths of ceramometal crowns versus several all ceramic crowns. AB - Fracture resistance to forces applied to the incisal edges of four types of anterior crowns was tested. Ceramometal crowns fractured at significantly higher values (720 psi) than the all-ceramic crowns (approximately 360 psi). No significant difference was found among the fracture values of the Dicor crowns, the aluminous porcelain jackets, and the crowns fabricated from Dicor veneered with aluminous body and incisal porcelain. PMID- 1403917 TI - The wear of enamel opposing shaded ceramic restorative materials: an in vitro study. AB - The wear rate of intact human enamel opposed by Olympia porcelain gold, Dicor, Ceramco porcelain, and externally shaded Dicor and Ceramco was investigated with an artificial oral environment. The enamel-material couples were subjected to 300,000 masticatory cycles at a maximal occlusal force of 13.4 N while they were continuously bathed with 37 degrees C deionized water. Both the enamel and material surfaces were analyzed by use of a three-dimensional surface monitoring computer program, AnSur, to record the removal of the material and the maximal loss of vertical height. The enamel opposing the externally shaded materials abraded two to five times more than that opposing the unshaded materials and 10 to 15 times more than enamel opposing gold. The wear rates for enamel opposing the gold and unshaded Dicor were similar both in the removal of material and in the loss in vertical height. PMID- 1403918 TI - The effect of adhesive luting agent-dentinal surface interactions on film thickness. AB - This study investigated the effect of luting agent-dentinal surface interactions on the film thicknesses of new adhesive luting agents. The method was in compliance with American National Standards Institution/American Dental Association (ADA) Specification No. 8 for zinc phosphate cement. In the control groups the luting agents were placed between two glass plates, as described in ADA Specification No. 8, but in the test groups the luting agents were positioned between a glass and a dentinal plate. The materials selected were zinc phosphate cement, glass ionomer cement, polycarboxylate cement, and a resinous cement with a dentinal bonding agent. A two-way analysis of variance was performed, and t tests were computed to compare glass with the dentinal plate within each material. Zinc phosphate and glass ionomer cements exhibited a significant decrease in film thickness when measured in contact with dentin, as compared with contact with the glass plate. However, polycarboxylate cement and the resinous cement with its dentin bonding agent showed a slight nonsignificant increase when contacting dentin, as compared with the glass plate. An explanation was offered and suggestions were made regarding future research. PMID- 1403919 TI - Shear strength of resin developed by four bonding agents used with cast metal restorations. AB - The evolution of the acid etch technique has made possible a more conservative approach to the fabrication of cast metal restorations. The resin bonding technique, however, places a greater burden for success on the selection of a bonding agent. This study examined the shear bond strength durability of cast metal restorations bonded to tooth structure with one of four metal adhesive bonding agents. Results indicated stronger bonds for restorations cemented with Panavia EX bonding agent than with any of the other bonding agents tested, both with and without exposure to thermal stress. Although it was one of the easier materials with which to work, Panavia EX bonding agent requires the additional step of applying an agent to prevent oxygen contact in the setting process. PMID- 1403920 TI - Method to measure the polymerization shrinkage of light-cured composites. AB - The polymerization shrinkage of light-cured dental composite resins has been reported to cause a marginal gap between the cavity wall and the restoration, leading to the premature and/or tensile stress failure of the composite restoration. This study measured the volumetric shrinkage of six light-cured posterior composites by measuring specific gravity differences between uncured and cured composite test specimens, using a modified version of ASTM method D792 "Specific Gravity and Density of Plastics by Displacement." The measured volumetric shrinkage ranged from 1.35% to 3.22%. PMID- 1403921 TI - Amalcore strength recovery following refilling of access preparations with amalgam. AB - After endodontic treatment through an amalgam core, the recommended procedure is to replace the entire core. This study examined the strength achieved by restoring the access openings with dental amalgam and reported the type of failure during strength testing. Seventy-two Dispersalloy 8 x 8 mm cylindrical specimens were produced using controlled condensation pressures. The specimens were randomized in three groups: (1) controls, (2) 3 mm access preparations wetted with mercury-rich amalgam before restoration, and (3) 3 mm access preparations restored unwetted. The specimens tested for compressive strength were separated in two subsets. The unwetted group demonstrated significantly less strength than the control and wetted group (p less than 0.05), while the unwetted and wetted groups revealed significantly less strength than the control group (p less than 0.05). The mean diametral tensile strength recovery for the wetted and unwetted groups was 76% and 69%, respectively. The qualitative assessment of the fracture zones indicated that wetted specimens exhibited more fractures through the new amalgam core than the unwetted specimens (p less than 0.05). It would appear that amalgam refilling of access preparations through amalgam cores has clinical potential. PMID- 1403922 TI - Bar attachments for overdentures with nonparallel abutments. AB - Bar attachments are easily fabricated and provide increased retention and support for overdentures. Nonparallel root abutments can preclude the routine use of bar attachments unless modifications are made in the design. This article reviews several existing techniques to successfully fabricate bar attachments in overdenture patients with nonparallel abutments. In addition, three alternative methods are presented for placing bar attachments on abutments with divergent roots. PMID- 1403923 TI - Comparison of the retentive properties of a sleeve cast crown/core system with crowns cemented to conventional cast cores. AB - The retention of the crown to the core substructure is of great importance for a successful restoration. The aim of this study was to compare the retentive values of the Flexi-Cast post and its sleeve crown/core complex with that of a crown cemented to a conventional cast post. Forty single-rooted teeth divided equally into four groups were used. Flexi-Cast crown and cores were cemented to Flexi Cast posts in groups 1 through 3. Group 4, the control group, comprised crowns cemented to conventional cast cores. Groups 1 through 4 had retentive values of 126.2, 135.5, 185.0, and 79.3 lb, respectively. Statistically, the increase in retention for all sizes of the Flexi-Cast crown and cores when compared with the control cast post and crown was found to be significant (p less than or equal to 0.0001). PMID- 1403924 TI - The value of radiographic predictors of the rate of mandibular residual ridge resorption. AB - This study tested the relationships between the rate of mandibular residual ridge resorption and the following two variables: cortical thickness at the gonion, and the proportion of cortical bone at the symphysis. These parameters were also compared between men and women. Measurements of cortical thickness at the gonion on panoramic radiographs were compared with similar measurements on lateral cephalometric radiographs. The results showed that neither cortical thickness at the gonion nor the proportion of cortical bone at the symphysis could be used as radiographic predictors of the rate of mandibular bone resorption. The rate of resorption was significantly greater in men than in women, while cortical thickness at the gonion in women was significantly less than that in men. Furthermore, the authors concluded that cephalometric and panoramic measurements should not be used interchangeably. PMID- 1403925 TI - Changes in the mandibular rest position after removal of remaining teeth and insertion of complete dentures. AB - A 24-month study was conducted to determine changes in the mandibular rest position after removal of the remaining teeth and insertion of complete dentures. A total of 24 patients with at least 10 teeth acting as occlusal stops were included in this study. Serial lateral cephalometric radiographs were made for each patient on four occasions (1) before extraction (2) 7 to 10 days after the initial denture insertion (3) 12 months later, and (4) 24 months later. Two angular measurements and one linear measurement were made for each radiograph and compared. A statistically significant increase in the face rest height with a tendency for posterior mandibular rotation was recorded between stages 1 and 2. This initial posterior rotation was followed by a gradual forward and upward movement, which finally brought the mandibular rest position even below the preextraction levels. The findings confirm the concept of the variability of posture and suggest that the mandibular rest position is an unreliable means of reestablishing the vertical dimension of occlusion that existed before extraction of the natural teeth. PMID- 1403926 TI - Denture base resins: comparison study of color stability. AB - Several denture base resins have been recently introduced that provide easier or faster processing. Although these materials have adequate strength properties, the color stability is also of interest. This study evaluated the color stability of five denture base acrylic resins and one denture base repair resin. The samples were subjected to conditions of accelerated aging to test color stability. Five samples of each material were processed and aged for 100 and 300 hours. The color stability was quantitatively measured using the Minolta Chroma Meter II. Color measurements were made before weathering and at 100 and 300 hours the color difference delta E was calculated for all samples. At 300 hours the color change of the materials was significantly different at p less than 0.01. It was found that: (1) the color of Lucitone Hy-pro and Acron was least affected by conditions of accelerated aging; (2) Triad, Accelar 20, and Perm demonstrated noticeable color changes; and (3) Compak-20 had an appreciable color change and was the least color-stable of the materials tested. PMID- 1403927 TI - Fatigue strength of cantilevered metal frameworks for tissue-integrated prostheses. AB - The design of the metal alloy framework in cantilevered sections of fixed tissue integrated prostheses, is critical. Several cross-sectional designs have been advocated, including the popular L-shaped beam, which permits the economical use of space for tooth placement. The fatigue strengths of 15 L-shaped cantilevered framework sections of the same metal alloy were tested. The castings were divided into three groups of five according to vertical wall heights of 4, 5, and 6 mm. Fatigue durability of each sample was determined by counting the number of cycles of vertical forces required to induce catastrophic failure. Statistical analysis revealed significant differences between all three groups in the cycles counted at failure (p less than 0.0019). Fatigue strengths improved significantly with increasing vertical wall height of the L-shaped cantilevered frameworks. In addition, beam flexure was shown to be indirectly proportional to fatigue strength. Theoretical beam deflection was calculated and shown to correlate with the actual beam deflection during the testing. Theoretical calculations in static bending specific for a cross-sectional design may aid in the predictability of fatigue strength. PMID- 1403928 TI - Retrieval of the resilient element in an osseointegrated implant system. AB - A fractured apical fragment of the resilient intramobile element within the IMZ dental implant cylinder is difficult to remove. The continued usefulness of the implant will be compromised if the fractured intramobile element is not removed. Two methods of retrieving the apical fragment without causing damage to the internal threads of the implant cylinder are described. PMID- 1403929 TI - Stress distribution around dental implants: influence of superstructure, length of implants, and height of mandible. AB - The stress distribution around dental implants was investigated by use of a two dimensional model of the mandible with two implants. A vertical load of 100 N was imposed on abutments or the bar connection. The stress was calculated for a number of superstructures under different loading conditions with the help of the finite element method. The length of the implants and the height of the mandible were also varied. A model with solitary abutments showed a more uniform distribution of the stress when compared with a model with connected abutments. The largest compressive stress was also less in the model without the bar. Using shorter implants did not have a large influence on the stress around the implants. When the height of the mandible was reduced, a substantially larger stress was found in the bone around the implants because of a larger overall deformation of the lower jaw. PMID- 1403930 TI - Phenytoin hyperplasia occurring under complete dentures: a clinical report. PMID- 1403931 TI - Periodontal and prosthodontic treatment of amelogenesis imperfecta: a clinical report. AB - A multidiscipline procedure has been described that provided prosthodontic restoration of esthetics and function for a patient with amelogenesis imperfecta. PMID- 1403932 TI - Effects of home bleaching preparations on composite resin color. AB - The lightening of teeth is done professionally by exposure to warm hydrogen peroxide solutions or at home with an active bleaching gel of perhydrol urea or carbamide peroxide. This study compared the effects of two commercial bleaching gels on the color of composite resin with those in a previous study using the dental office technique. Commercial composite resins test specimens were exposed to the bleaching gels or water (control) for 312 hours at 37 degrees C at 100% relative humidity. Color change value was calculated with before-and-after solution exposure L*a*b* color values. ANOVA (alpha = 0.01) revealed no differences in the color of the specimens after use of the test solutions. All color change values were less than 2 or the normal limit of visual acuity. No visual color change was evident for these composite resins. The at-home method recorded no shade-altering effects compared with the professional technique, which created a noticeable color change. PMID- 1403933 TI - Accuracy and bond strength of reversible with irreversible hydrocolloid impression systems: a comparative study. AB - Combinations of three reversible hydrocolloids with five irreversible hydrocolloids were evaluated for dimensional accuracy and bond strength. A stainless steel model representing two teeth prepared for a fixed partial denture was designed for an accuracy study. The recordings were made with a measuring microscope, and the tensile bond strength was determined with an Instron Universal Testing instrument. The accuracy of these materials was clinically acceptable, and the resulting models were suitable. The materials distributed by a common supplier exhibited better tensile strength, although one irreversible hydrocolloid, Jeltrate, performed well in the noncompanion combination groups. This reversible with irreversible hydrocolloid combination impression has an advantage compared with the traditional reversible hydrocolloid impression, because it does not require elaborate, expensive conditioning equipment and water cooled trays. PMID- 1403934 TI - Fatigue life of three core materials under simulated chewing conditions. AB - There has been an increase in the use of prefabricated post systems to restore endodontically treated teeth. Various restorative materials are being used as core buildups on these posts. The purpose of this study was to compare three core materials that are used with prefabricated stainless steel posts. Two types of prefabricated posts were placed in extracted teeth, followed by core buildups in amalgam, composite resin, or glass ionomer. The teeth were prepared for full cast crowns with the margins of the crown preparation extending 0.5 to 1.0 mm below the margins of the core buildup. Crowns were fabricated and cemented with zinc phosphate cement. A custom-designed chewing machine was used to cyclically load the teeth with vertical and horizontal forces for one million cycles or until failure occurred. Results indicated highly significant differences in the survival of the post-core-crown restorations depending on which core buildup material was used. Amalgam cores had the lowest failure rate, followed by composite resin cores. All teeth restored with crowns over glass-ionomer core buildup failed. The type of prefabricated post used had no effect on the survival of the post-core-crown restorations regardless of the core buildup used. PMID- 1403935 TI - Recording centric and eccentric occlusal disturbances with a new recording device. AB - A recording device termed a "Kleinrok Functiograph" was introduced to simultaneously document condylar- and tooth-guided mandibular movements on the same plate. The Functiograph instrument permitted objective monitoring of mandibular movement without tooth contact, with all tooth contacts, and allowed analysis of the correlation of these two recordings. After 10 years of conducting investigations on centric occlusion using the Functiograph instrument combined with clinical, radiographic, and electromyographic studies, it was possible to differentiate the horizontal Functiograph recordings of normal and disturbed centric occlusion at a clinically acceptable vertical dimension. Two types of centric occlusal disturbances were classified to accelerate diagnosis and standardize communication. PMID- 1403936 TI - Tensile bond strengths of three chemical and one electrolytic etching systems for a base metal alloy. AB - This study compared the tensile bond strength of Rexillium III disks etched by three chemical etching systems and the electrochemical etching technique. Cast Rexillium III disks were etched by the following etching systems: electrochemical, Assure-Etch, Met-Etch gel, and Etch-It gel. Thermocycled samples were loaded to failure in tension on an Instron testing machine using a crosshead speed of 5 mm/minute. Samples etched electrochemically yielded significantly greater bond strengths than those etched chemically (p less than 0.05). The rank of the groups was: Electrochemical greater than Assure-Etch = Met-Etch greater than Etch-It. Scanning electron micrograph evaluations of the etching patterns supported the bond strength determinations. PMID- 1403937 TI - Improved retention of acid-etched fixed partial dentures: a longitudinal study. AB - Debonding of acid-etched fixed partial dentures has been a problem since their introduction. A study was conducted to determine whether this problem could be resolved by modifying the mechanical retention of tooth preparations. Retentive grooves were prepared at the line angles to create mechanical locks for the resin bonded fixed partial denture. The 4-year retention of posterior resin-bonded fixed partial dentures improved from 60% to 95% by the placement of the proximal grooves. This study was conducted in a dental school clinic during a period of 10 to 52 months. The results demonstrated that design modifications were necessary to improve clinical longevity so that the restoration could be considered "permanent" in the traditional sense. The less-experienced dentist may be more confident of the treatment with the recommended modifications and projected longevity. PMID- 1403938 TI - Microleakage of composite resin and glass ionomer cement restorations in retentive and nonretentive cervical cavity preparations. AB - Ketac Fil glass ionomer cement (GIC) and Scotchbond 2 dentinal bonding agent (DBA)/Silux Plus composite resin restorations were inserted in cervical cavity preparations of extracted human teeth. After thermocycling, the specimens were invested and sectioned longitudinally and horizontally through the center of the restoration. Microleakage was evaluated as a ratio of the extent of methylene blue dye penetration at the tooth-restoration interface. Although all restorations exhibited leakage, both the GIC and bonded composite resin restorations recorded less leakage in retentive than in nonretentive cavity preparations. Composite resin restorations in nonretentive cavity preparations showed significantly more dye penetration toward the pulpal chamber than the GIC restorations. Ketac Fil GIC restorations inserted without a matrix strip exhibited less leakage than those with a matrix strip. The most desirable results were recorded with Scotchbond 2 DBA/Silux Plus composite resin restorations in retentive preparations. PMID- 1403939 TI - Enhancement of antimicrobial properties of cavity varnish: a preliminary report. AB - Bacterial contamination beneath amalgam restorations has been a problem in restorative dentistry. Cavity varnish improves the marginal seal but possesses no antibacterial properties, and chlorhexidine gluconate is a known antimicrobial substance. This study investigated the efficacy of a chlorhexidine gluconate/cavity varnish mixture against Streptococcus mutans, S. salivarius, and Escherichia coli. The in vitro results indicated that the addition of chlorhexidine gluconate to cavity varnish improved its antimicrobial properties. PMID- 1403940 TI - The effect of cold treatment on the physical properties of stainless steel and titanium alloy endodontic posts. AB - This study determined whether cold treatment at -96 degrees C affected the mechanical properties of various compositions and sizes of the Flexi-Post system. The experiment was divided into four groups of posts. The two control groups were made up of untreated stainless steel (50 posts) and titanium alloy (40 posts). The two remaining cold-treated groups were made up of stainless steel (50 posts) and titanium alloy (40 posts). In each instance the bending or breaking forces were tested on a universal testing machine. Stainless steel Flexi-Post samples showed a significant (p less than 0.05) increase in strength, whereas titanium alloy posts showed no significant increase in strength as a consequence of the cold treatment. PMID- 1403941 TI - An in vitro evaluation of simplified quantitative diagnostic aids for detection of Candida albicans. AB - Sensitivities and abilities of quantitative detection for Candida albicans of five simplified diagnostic aids for candidosis or denture stomatitis--Microstix Candida, Stomastat medium, Mizuno- Takada medium, CA-TG medium, and "milk test"- were examined in vitro, and the characteristics or the indications for clinical use of these summarized. PMID- 1403942 TI - Dimensional accuracy and stability of acrylic resin denture bases. AB - Proponents of injection molding systems have claimed a number of benefits over conventional press-pack dough molding systems. The aim of this study was to evaluate a recently developed injection (dry heat) procedure of processing compared with press-pack dough molding utilizing three curing cycles. The dimensional accuracy and stability of acrylic resin bases produced by the two molding procedures were compared. Dimensional changes were assessed over a period of 4 months using an optical comparator. The results demonstrate that baseplates produced by the injection molding procedure exhibit less shrinkage than those produced by the conventional press-pack procedures. PMID- 1403943 TI - Application of the rotational path design concept to a removable partial denture with a distal-extension base. AB - Biomechanical considerations for use of the rotational path design concept to construct a removable partial denture for a patient with a tooth-bounded ridge on one side and a distal-extension ridge on the opposite side are presented. The various axes and arcs of rotation that occur during masticatory function are identified and their effects on the prosthesis and supporting structures are analyzed. Sequential steps in the necessary surveys of the master cast are enumerated. Critical details for the most effective and least deleterious placement of the rigid retentive element on the mesial surface of the posterior molar abutment (on the tooth-bounded ridge) are described. PMID- 1403944 TI - Effects of environmental factors on maxillofacial elastomers: Part III--Physical properties. AB - The physical properties of four currently used and two recently introduced maxillofacial prosthetic materials were evaluated after the materials were subjected to the following seven environmental variables: natural weathering, normal aging, two types of adhesives, two types of cleaning agents and cosmetics. Ultimate tensile strength, percent elongation, tear strength, and Shore A hardness were evaluated. The physical properties recorded for the currently used materials were consistent with previous studies. Although the properties of the recently introduced materials were similar to those currently in use, one of the new materials, A-2186, showed high strength values, although it was one of the softest materials tested. Unfortunately, this new material lost these advantageous characteristics as it was weakened and made harder by most of the tested environmental variables. PMID- 1403945 TI - Naturally occurring undercuts in the retention of an interim oculofacial prosthesis. AB - The use of adhesives in retaining maxillofacial prostheses has been advocated and applied for many years. Implant placement has reduced the need for adhesives in some patients but is impractical when ablative surgery is followed by radiation treatment. A technique is described that permits the rapid fabrication of an oculofacial prosthesis that uses naturally occurring orbital undercuts for retention, rather than adhesives that may further irritate radiated tissues. PMID- 1403946 TI - A study of 589 consecutive implants supporting complete fixed prostheses. Part I: Periodontal aspects. AB - Ninety-one consecutive edentulous patients who had been treated by means of fixed prostheses (n = 103) supported by Branemark implants (n = 589) were examined. Eighteen fixtures (3%) failed to integrate. After a mean loading time of 32 (range 6 to 80) and 38 months (range 5 to 83) for fixtures in the maxilla and mandible, respectively, an additional 12 fixtures lost integration. The cumulative failure rate for individual fixtures after 6 years was 8.4% and 5% for maxillae and mandibles, respectively. Only one patient had to revert to complete dentures. For fixtures in the maxillae, the mean marginal bone loss was 0.7, 0.1, and 0.2 mm for each of the first 3 years of loading, respectively; for fixtures in mandibles, the corresponding values were 0.7, 0.2, and 0.1 mm. The loss in marginal bone height was equal in both jaws and was not related to bleeding on probing or to the preoperative resorption anatomy. PMID- 1403947 TI - Altered sensation following mandibular implant surgery: a retrospective study. AB - To determine the prevalence of complications involving altered sensation after implant surgery in the mandible, a retrospective questionnaire study was conducted of 266 patients treated with osseointegrated implants. Of the responding patients (80%), 37% reported altered sensation following implant surgery, with long-term changes occurring in 13% of patients. In more than 60% of symptomatic patients the onset was within 1 week of the first stage of surgery and most frequently involved the lip and chin. Resolution of transient changes usually occurred within 6 months and the majority of patients who reported alterations in sensation believed that the benefits of the implant surgery outweighed the disadvantages experienced. The prevalence of altered sensation was significantly higher in women compared with men and in those with a history of diabetes. These data indicate the need for prospective studies to further evaluate altered sensation after mandibular implant surgery so that specific risk factors can be identified and more accurate information made available to prospective patients. PMID- 1403948 TI - Kinesiographic three-dimensional evaluation of mandibular border movements: a statistical study in a normal young nonpatient group. AB - Mandibular border movements were studied in a group of 74 healthy young men and women with sound dentitions and class I molar relationships. Movements were directly performed by the subjects and recorded with a mandibular kinesiograph, and slopes of the first millimeters of motion in the anterior and lateral guidances were calculated. In anterior guidance, the sagittal plane slope was steeper in men than in women, whereas the horizontal plane slope showed no gender differences. In the lateral guidances, frontal plane slopes were steeper in men than in women, with no side differences. The horizontal plane slope presented no side or sex differences. Most of the subjects demonstrated asymmetric guidances for both protrusive and the laterotrusive movements. These findings suggest that criteria for defining the norm should include asymptomatic asymmetry instead of strict morphologic symmetric appearance. PMID- 1403949 TI - Evaluation of a technique for recording temporomandibular joint sounds. AB - Analysis of temporomandibular joints sounds may contribute to the differential diagnosis of temporomandibular joint disorders. In this article an advanced system for the recording of joint sounds is presented. The method proved to be reliable. The problem of filtering out artifacts has been solved to a great extent but not completely. Temporomandibular joint sounds measured with this technique vary considerably in energy, frequency spectrum, and peak-to-peak amplitude over 3 months, as well as within 1 day. These differences seem to reflect natural variations in joint sounds caused by the physical impossibility of performing identical jaw movements. The results indicate that joint sound characteristics do not yet offer a solid basis for inferences concerning the development of temporomandibular joint abnormalities in the clinical setting. PMID- 1403950 TI - Characterization of acquired denture pellicle from healthy and stomatitis patients. AB - Little information is available about the acquired pellicle layer that is formed on denture surfaces or its role in regulating microbial colonization of the prosthetic surface. Because denture-induced stomatitis is associated with increased numbers of Candida albicans and other microorganisms on the denture surface, the acquired denture pellicle (ADP) may play a role in modulating this colonization. This study examined and compared ADP from healthy patients and patients with stomatitis by chemical and immunochemical methods. The ADP was found to be composed of a selectively adsorbed layer containing salivary amylase, high molecular weight mucin (MG1), lysozyme, albumin, and sIgA. Salivary cystatins, proline-rich proteins, and low molecular weight mucin (MG2) were not detected. ADP amino acid composition was distinct from any of the ductal salivas, but had many similarities with enamel pellicle. Immunoblots of ADP from patients with stomatitis identified additional serum components, degradation products, and C. albicans cell components that were not detected in ADP from healthy patients. Quantification of these molecules in ADP could lead to a diagnostic test for oral mucosal disease underlying a denture base. Identification of specific molecules in denture pellicle that promote adhesion of C. albicans may elucidate a mechanism of fungal cell colonization on the denture surface. Future studies that chemically modify the denture acrylic resin surface to immobilize antimicrobial proteins may be a means of decreasing pathogenic plaque development. PMID- 1403951 TI - Leaching of nickel, chromium, and beryllium ions from base metal alloy in an artificial oral environment. AB - The use of base metal alloys in dentistry has gained wide popularity in recent years. However, claims of their safety have not been universally accepted. An artificial oral environment capable of reproducing three-dimensional force movement cycles of human mastication was used to determine whether nickel, chromium, and beryllium ions were leached from base metal alloy. Twelve pairs of crowns were articulated in the following combinations: metal versus metal, metal versus enamel, metal versus porcelain, and metal versus metal without chewing as a control. In a simulated 1-year period of mastication, the results showed that nickel and beryllium metals were released both by dissolution and occlusal wear. These findings suggest that if these conditions occur in the oral cavity, the stability of base-metal alloys is subject to question. Further studies are needed to determine whether the leaching reported has long-term consequences for patients receiving base metal restorations. PMID- 1403952 TI - Removable magnetic dental attachment that permits magnetic resonance imaging. AB - Magnetic dental attachments cause magnetic resonance image (MRI) degradation. A new magnetic dental attachment that allows removal of magnetic parts to exchange them for nonmagnetic parts was developed and tested. It allows high quality MRI with no change in occlusal vertical dimension. A volunteer test subject with combinations of attachments in place was examined by MRI. The images produced showed no degradation or distortion. Magnetic attachments for overdentures or maxillofacial prostheses should be removable to permit use of MRI. PMID- 1403953 TI - An indicator for fitting castings to a die. AB - This article describes a procedure for making an indicator to be used in fitting a casting to a die. It also describes how to use the indicator in the laboratory. The materials for making the indicator are inexpensive, present no health hazard, and are readily available at any arts and crafts store. PMID- 1403954 TI - Adaptation of overdenture abutments with visible light-cured resin. PMID- 1403955 TI - An advantage of the direct post and core technique. PMID- 1403956 TI - Temporary soft liners: a modified curing technique to extend liner longevity. AB - A modified curing technique that will extend the useful clinic life of temporary soft liners has been described. This technique offers the following distinct advantages over the traditional method of intraoral curing: (1) a liner that is less porous; (2) a liner that maintains its resilience intraorally for extended periods; (3) a liner that exhibits minimal discoloration over time; (4) increased density that allows adjustments to be made when necessary; and (5) minimized separation from the acrylic resin denture base. PMID- 1403957 TI - Palatal contour guide for positioning retentive framework for obturation for a hemimaxillectomy patient. PMID- 1403958 TI - Change in the air. PMID- 1403959 TI - Establishing the role of the clinical nurse specialist in postanesthesia care. AB - The postanesthesia clinical nurse specialist (CNS) is a relatively new and developed role, one that is needed and that can be justified in the specialty of postanesthesia care nursing. This article describes a model with components of expert practitioner, educator, researcher, consultant, and liaison. The sub-role of change agent pervades all other roles of the postanesthesia CNS. Establishment of the role is examined using change theory. Fitting this specialty CNS into the organization is briefly examined through systems theory. Integrating the role into the system requires role making, role taking, and steps to reduce the stress associated with establishing a new role. Communication with involved subsystems, such as postanesthesia staff nurses, management, anesthesia staff, and physicians, is vital to the success of the role. Through education and interaction, significance of the role can be demonstrated to establish the postanesthesia CNS as a vital partner in postanesthesia nursing practice. PMID- 1403960 TI - Collaborative governance in the postanesthesia care unit. AB - The administration at Schumpert Medical Center, Shreveport, LA, is committed to empowering the nursing staff. Due to this commitment, the postanesthesia nurses developed a collaborative governance program that is based on empowerment. This article discusses how to begin the development and implementation process, address staff concerns, and facilitate acceptance of the finished program by the staff. This program has become a successful model for the collaborative governance program at the author's hospital and has resulted in a stimulating and caring working environment for the professional. PMID- 1403961 TI - In a small way. PMID- 1403962 TI - Practical points in the management of malignant hyperthermia. AB - It is the purpose of this article to discuss malignant hyperthermia, including its incidence, pathophysiology, and treatment. Anesthetic implications and PACU nursing considerations are also addressed. PMID- 1403963 TI - Hemodynamic monitoring: what it tells you and what it doesn't, Part I. PMID- 1403964 TI - Hemodynamic monitoring: what it tells you and what it doesn't, Part II. PMID- 1403965 TI - Validation of concepts: the next step in instrument development for postanesthesia studies. AB - Validation of concepts through descriptive research is a major step in instrument development. The concept of hypothermia as observed in the postanesthesia patient is discussed, and data are compared with the North American Nursing Diagnosis criteria of hypothermia. What emerges from the data are items specific to postanesthesia patients, which have been labeled as inadvertent postanesthesia hypothermia (IPH). Thus, the importance of concept analysis in instrument development is emphasized because the omission of this step from instrument development may result in lack of clarity or "fuzzy data" in what is to be measured. PMID- 1403966 TI - Medical device reporting: a new challenge for perioperative nurses. AB - A variety of illnesses and other complications have been attributed to problems resulting from use of medical devices, implants, and instruments. A new law has implications for all health care facilities using medical devices. The Safe Medical Devices Act (SMDA) of 1990 mandates the reporting of complications related to the use of medical devices to the United States Food and Drug Administration. Reporting requirements of the SMDA could challenge the efficiency of information systems in health care facilities and add to the responsibilities of staff nurses. In the following article, the author discusses some implications of the new law. PMID- 1403967 TI - Silence: a powerful resource. PMID- 1403968 TI - Emergence and human conduct. AB - Emergence, the occurrence of novel, unpredictable human behavior, is an inherent aspect of human experience on both the individual and collective levels. In this article, we considered the ubiquitous nature of emergent events, indicated some of the ways such events manifest themselves, analyzed the personal and interpersonal processes that give rise to them, and suggested some of their implications for psychology and the other social sciences. Given the inescapable presence of emergence in human conduct, a redefinition of the goals and scope of social science may be desirable. PMID- 1403969 TI - Memory structure in the processing of advertising messages: how is unusual information represented? AB - Two models of memory structure--schema-copy-plus-tag (Graesser & Nakamura, 1982; Schmidt & Sherman, 1984) and associative-network/depth-of-processing (Craik & Lockhart, 1972; Hastie & Kumar, 1979)--were tested in a 2 x 2 between-subjects design. Type of argument (typical vs. atypical) and measurement interval (immediate vs. 2-day delay in recognition and recall) were manipulated in a print advertising context. Results indicated that atypical arguments (unusual information) prompt deeper processing of the entire message (implying an associative-network memory structure) rather than some part of the message (as would be hypothesized by the schema-copy-plus-tag formulation) and that this effect prevails under both immediate- and delayed-measurement conditions. PMID- 1403970 TI - Preventing smoking: evaluating the potential effectiveness of cigarette warnings. AB - We examined the potential effectiveness of U.S. government cigarette warnings in preventing adolescent smoking. In Study 1, 112 seventh graders rated the effectiveness of four currently required warnings and four possible other warnings and answered questions about the meaning of certain words in the warnings. In Study 2, 115 seventh graders attempted to recall the four current warnings; in Study 3, 103 eighth and ninth graders read all eight warnings one day and tried to recall them the next day. In Study 4, 25 seventh graders participated in a focus session in which they discussed the effectiveness of each of the eight warnings. The results of the studies showed that the four different evaluation strategies had convergent validity and that two current warnings and two proposed warnings are significantly more potentially effective than the other two current warnings. Our results also provided information about why some warnings are more potentially effective than others. PMID- 1403971 TI - Gender, academic achievement, and preferences for cooperative, competitive, and individualistic learning among African-American adolescents. AB - In this study, we investigated the relationships among gender, academic achievement, and student preferences for cooperative, competitive, and individualistic learning in a sample of 136 African-American adolescents enrolled in sixth and seventh grades in a school in Georgia. We used the Learning Preference Scale for Students (LPSS; Barnes, Owens, & Straton, 1978) to measure cooperative, competitive, and individualistic preferences. Three two-way ANOVAs (Gender x Academic Achievement) were conducted, in which the three learning preferences were the dependent variables. Gender had a significant effect on the preference for cooperative learning, with girls reporting a higher preference for this method than boys did. For the other two learning preferences, no significant gender differences were found. Academic achievement did not correlate significantly with any of the three learning preferences. A two-way interaction between gender and academic achievement was observed for competitive learning preferences. Girls' preferences for competition increased as academic achievement increased; boys' preferences for competition decreased as academic achievement increased. PMID- 1403972 TI - Friendship similarity during early adolescence: gender and racial patterns. AB - We studied the relationship of reciprocity, gender, and racial composition (Caucasian, African American, cross-race) of adolescent friendship dyads to similarity and proximity in 136 young adolescents. We found that adolescents selected friends who were of the same gender and race and that female dyads were more similar than male dyads on verbal achievement and several personality dimensions. Caucasian dyads were more similar than African American dyads on verbal achievement, mental alertness, and dominance. African American adolescents had more contact with their best friends outside school, whereas Caucasian adolescent friends had more in-school contact. African American students had fewer reciprocal relationships than the Caucasian students. Cross-race friendships were less reciprocal than same-race friendships. Race and gender were important in determining friendship patterns. Similarity and proximity were more important than reciprocity in understanding early adolescent friendships. PMID- 1403973 TI - Personality traits of a group of young adults from different family structures. AB - The impact of parental divorce and remarriage and young adults' gender on second order personality traits, such as extraversion, anxiety, tough poise and independence, was examined. The responses of 227 young adults on the Sixteen Personality Factor Questionnaire (16PF; Cattell, Eber, & Tatsuoka, 1970) were subjected to a parametric multivariate analysis of variance. Results revealed significant differences between the anxiety scores of the young men and women as well as between those of the three different family-structure groups, but divorce and remarriage was not associated with either positive or negative personality development in this sample. PMID- 1403974 TI - Self-concept and sociometric outcomes: a comparison of only children and sibling children from urban and rural areas in the People's Republic of China. AB - We investigated differences in self-concept between 360 only children and 555 sibling children in the sixth grade of three urban schools and three rural schools in the People's Republic of China. Peer perceptions and teacher perceptions were also collected using sociometric measures. Self-concept was determined by the Self-Perception Profile for Children (Harter, 1985). Comparisons of sibling children and only children showed no differences on self concept; however, urban residents had higher self-concept scores than children from rural areas, and boys scored higher than girls. No significant interaction effects between sibling status, gender, and residence were found. PMID- 1403975 TI - Reaction times and intelligence in Korean children. AB - Nine-year-old Korean children (N = 299) were tested for reaction time (RT) and intelligence measured by Raven's Standard Progressive Matrices. Reaction times were broken into decision times and movement times and into three degrees of complexity. The results showed low but generally statistically significant correlations between decision times and intelligence. Generally, no significant differences existed between movement times and intelligence. Boys showed significantly faster movement times than girls did. PMID- 1403976 TI - The role of the object in drive cathexis and psychosexual development. AB - Alternate axes are explored in the orthodox formulation of drive cathexis and psychosexual development, with implications for corresponding object relation modes engendered by these processes. Somatic and defensive aspects are shown to impact on the function of the "other" as the individual matures. The separation/individuation process is subsumed into this overall developmental continuum, and the centrality of the object as a focus in cathexis and drive delineation is critically evaluated. The homeostatic notion of equilibration is appealed to in synthesizing the factors emerging from the analysis. PMID- 1403977 TI - The relationship of impulsiveness to psychoticism and extraversion in elderly psychiatric patients. PMID- 1403978 TI - Replications and resolutions: dualistic belief, personality, religiosity, and paranormal belief in Australian students. PMID- 1403979 TI - Redescription of Phacodinium metchnikoffi (Ciliophora, Hypotrichida): general morphology and taxonomic position. AB - Living and stained specimens of Phacodinium metchnikoffi, collected near Madrid, Spain, were studied under light microscopy. Infraciliature was stained using a silver-impregnation procedure. The somatic infraciliature is composed of a relatively small number of discontinuous kinetics, formed by groups of few kinetosomes (pallets). The buccal ciliature is composed of an adoral zone of membranelles and a paroral formation otherwise unknown in ciliates, with many short kineties, which lie on a rigid stem. We propose that P. metchnikoffi is a primitive hypotrich and, consequently, we present a new classification system for hypotrichs. PMID- 1403980 TI - Penetration of the mosquito (Aedes aegypti) midgut wall by the ookinetes of Plasmodium gallinaceum. AB - We observed Plasmodium gallinaceum ookinetes in both intracellular and intercellular positions in the midgut epithelium of the mosquito Aedes aegypti. After epithelial cell invasion intracellular ookinetes lacked a parasitophorous vacuolar membrane and were surrounded solely by their own pellicle. Thus, the ookinete in the midgut epithelium of the mosquito differs from erythrocytic and hepatic stages in that the parasite in the vertebrate host is surrounded by a vacuole. The midgut epithelial cytoplasm around the apical end of invading ookinetes was replaced by fine granular material deprived of normal organelles. Membranous structure was observed within the fine granular area. Most ookinetes were seen intracellularly on the luminal side and intercellularly on the haemocoel side of the midgut epithelial cells. These observations suggest that the ookinete first enters into the midgut epithelial cell, then exists to the space between the epithelial cells and moves to the basal lamina where the ookinete develops to the oocyst. PMID- 1403981 TI - Trypanosoma cruzi infection of BSC-1 fibroblast cells causes cytoskeletal disruption and changes in intracellular calcium levels. AB - The disruption of vimentin and actin filaments of host BSC-1 fibroblast cells by Trypanosoma cruzi was investigated using a mouse monoclonal anti-vimentin antibody and rhodamine phalloidin, respectively. Indirect immunofluorescence microscopy demonstrated that infection of BSC-1 cells by T. cruzi caused disruption of both cytoskeletal components. The disruption was greater as infection progressed. Mechanisms other than mechanical ones may play a role in the disruption since disrupted cytoskeletal elements were well removed from the parasites. In the determination of intracellular calcium concentrations using Fura-2 AM, infected and uninfected cells both showed an initial increase in intracellular calcium levels. At later times of infection (3 to 5 days), intracellular calcium levels of infected cells were significantly lower than those of control cells. There was no specific localization of intracellular calcium in the infected host cells as determined by image analysis. PMID- 1403982 TI - Determination of taxonomic status of pathogenic and nonpathogenic Entamoeba histolytica zymodemes using isoenzyme analysis. AB - Entamoeba histolytica infection results in either asymptomatic colonization or invasion of host tissues leading generally to clinical symptoms. Zymodemes studies have demonstrated a correlation between isoenzyme profiles and clinical presentation. Thus, strains have been attributed to pathogenic or nonpathogenic groups according to their zymodeme. To determine the taxonomic relationship of these two groups, the isoenzyme profiles of 14 loci of 38 E. histolytica strains (pathogenic and nonpathogenic) and seven strains of other species of the same genus were analyzed. Genetic distance analysis clearly demonstrates the existence of two separate groups within the species E. histolytica. PMID- 1403983 TI - Surface domains in the pathogenic protozoan Tritrichomonas foetus. AB - The quick-freezing and freeze-etching techniques were used to analyze surface domains of Tritrichomonas foetus. The surface of the protozoan body was not smooth, presenting surface projections, except on the flagellar surface. Images of the actual surface of the anterior flagella revealed the presence of intramembranous particles that form rosettes, as observed on the protoplasmic fracture face. They may represent integral transmembrane proteins exposed at the cell surface. Surface specializations were also observed at the flagella base and where the recurrent flagellum attaches to the cell body. PMID- 1403984 TI - Sporulation of Marteilioides branchialis n. sp. (Paramyxea) in the Sydney rock oyster, Saccostrea commercialis: an electron microscope study. AB - The ultrastructure of sporulation of a new parasite, Marteilioides branchialis (Paramyxea), in the Sydney Rock oyster, Saccostrea commercialis, is described. The development is typical of other Paramyxea whereby a stem cell internally cleaves a secondary cell contained within a vacuole. It differs from other species in the phylum in that each secondary cell produces a single spore composed of two concentric cells, one within a vacuole of the other. This type of sporulation represents the simplest of all known Paramyxea. Infection results in focal gill lesions and was observed concurrently with an epizootic of another paramyxean, Marteilia sydneyi. PMID- 1403985 TI - The immobilization antigens of Tetrahymena thermophila are glycoproteins. AB - The four immobilization antigens controlled by the SerH locus in Tetrahymena thermophila have been isolated and partially characterized (Doerder, F.P. & Berkowitz, M.S. 1986. Purification and partial characterization of the H immobilization antigens of Tetrahymena thermophila. J. Protozool., 33:204-208). We show here, using immunoprecipitation and electrophoresis after labeling with 35S-methionine, 14C-mannose, 14C-glucosamine, and N-Acetyl-D-[l-3H]glucosamine, that these proteins are glycosylated. We suggest the immobilization antigens in Tetrahymena may be anchored to the surface membrane by phosphatidylinositol glycans. PMID- 1403986 TI - Giardia lamblia: ultrastructural study of the in vitro effect of benzimidazoles. AB - Axenically grown Giardia lamblia trophozoites treated with low concentrations of the benzimidazole carbamates albendazole and mebendazole detach from glass culture tubes and lose viability. Scanning electron microscopic observations revealed that these drugs produce grotesque modifications of the cell shape of the parasite and disassembly of the adhesive disc. Transmission electron microscopy showed several stages of the fragmentation of adhesive discs with dispersion of microtubules and microribbons in the cytoplasm. Flagella appeared undamaged. In drug-treated trophozoites electron-dense precipitates were selectively deposited on microtubules and microribbons. The results indicate that the antigiardial effect of benzimidazoles is the result of binding to microtubules and subsequent alterations of the cytoskeleton. The electron microscopic observations also suggest that the drugs may bind to microribbon components of the adhesive disc, possibly giardin proteins. PMID- 1403987 TI - The interface between air and water: a perturbation source eliciting adaptive behaviour in ciliates. AB - Interference with the water-air interface, both direct (by contact with a flat, rigid surface) and indirect (by inducing a meniscus) caused the ciliated protozoa we investigated to actively collect in the water column or on the substrate directly under the area of altered surface tension. A crowding effect is observed in this "rest area" reaching plateau values within one hour after onset of the experiment. The simple experimental procedures described here induced analogous behaviour in both Paramecium caudatum (a swimmer) and Oxytricha bifaria (a crawler). The ciliates seem in this reaction to be seeking a refuge from vibrations transmitted by the free interface. Our discovery is discussed in its implications for the adaptive biology and ecology of these micro-organisms. PMID- 1403988 TI - Localization of a Toxoplasma gondii rhoptry protein by immunoelectron microscopy during and after host cell penetration. AB - We immunolocalized a Toxoplasma gondii rhoptry protein (ROP1) before and after parasite host cell invasion of human fibroblasts and TG180 murine sarcoma cells by electron microscopy and immunogold labeling using either a monoclonal antibody (Tg49) or a monospecific rabbit antiserum (alpha 249). At all stages of parasite growth ROP1 was found within the body but rarely within the peduncle of rhoptries, even in those that appeared empty. Immediately after host cell invasion ROP1 was associated with the parasitophorous vacuole membrane. Within hours after invasion the amount of ROP1 immunodetectable on the parasitophorous vacuole membrane was markedly decreased. The localization of ROP1 suggests a role in the early establishment of infection in host cells, consistent with previous work that has indicated that monoclonal antibodies to ROP1 (including the one used in these studies) interfere with the phenomenon of penetration enhancement. PMID- 1403989 TI - Schizogonic development of Leucocytozoon smithi. AB - The schizogonic development of Leucocytozoon smithi in the liver of experimentally infected turkey poults was examined by electron microscopy. Following intraperitoneal injection, sporozoites migrated to the liver and entered hepatic cells to become intracellular trophozoites. Three to four days post inoculation (PI), trophozoites underwent asexual multiple fission known as merogony or schizogony. Two generations of schizonts were observed. The primary or first generation schizonts, abundant on day 4 PI, appeared as interconnected cytoplasmic masses (pseudocytomeres). Each pseudocytomere was enclosed by a membranous vacuole and contained varying numbers of nuclei. As nuclear division and growth of the schizonts continued, larger discrete cytoplasmic masses or cytomeres were formed with rhoptries and multiple nuclei in various stages of division. Synchronous multiple cytoplasmic cleavage of the schizont resulted in the formation of numerous uninucleate merozoites. Second generation schizonts, which developed from hepatic merozoites released from primary schizonts, were abundant in hepatocytes on day 6 PI. Although tissue samples from liver, lung, spleen, kidney, intestine, brain, blood vessels and lymph nodes were examined, schizogonous forms were observed in liver only. No megaloschizonts were detected in any host tissue examined. Schizogonic development was completed by day 7 PI as merozoites developed into gametocytes within mononuclear phagocytes. PMID- 1403990 TI - Auditory sensitivity of the cichlid fish Astronotus ocellatus (Cuvier). AB - Auditory sensitivity was determined for the oscar, Astronotus ocellatus, a cichlid fish that has no known structural specializations to enhance hearing. Trained A. ocellatus behaviorally responded to sound stimuli from 200 Hz to 800 Hz with best sensitivity of 18 dB (re: 1 mubar) to 21 dB for frequencies between 200 and 400 Hz. This is significantly poorer than hearing sensitivity for fish classified as hearing specialists, but well within the range of hearing capabilities reported for non-specialist teleost species. PMID- 1403991 TI - The influence of stimulus duration on the delay tuning of cortical neurons in the FM bat, Myotis lucifugus. AB - 1. Echolocating bats use echo delay as the primary cue to determine target distance. During target-directed flight, the emitted pulses increase in repetition rate and shorten in duration as distance decreases. To determine how these parameters affect the delay tuning of neurons in the auditory cortex of the awake bat, Myotis lucifugus, we examined the responses of 104 delay-sensitive neurons as the pulse repetition rate (PRR) and duration were independently varied. Stimulus duration of 4, 2 and 1 ms and PRR of 5-100/s were used for both the pulse and echo to determine delay sensitivity. These parameter ranges span those used during the search, approach, and the initial terminal phases of echolocation. 2. As the stimulus duration was shortened, the range of PRRs for delay sensitivity was extended to higher rates in 41% of the neurons, narrowed or disappeared in 40%, and remained unchanged in 4%. The remaining 15% were not categorized since it was not possible to determine a trend in which the range of delay-sensitive PRRs changed with stimulus duration. 3. Three types of tracking neurons (i.e., neurons that change their best delay during target-directed flight) were found. For the first type, the best delay (BD) shortened with shorter stimulus duration, for the second type, BD shortened with both shorter stimulus durations and higher PRRs, and for the third type, BD shortened with higher PRRs. 4. These results suggest that the stimulus parameters of sonar emission influence delay tuning and hence processing by cortical neurons in FM bats. PMID- 1403992 TI - Temperature coupling in cricket acoustic communication. I. Field and laboratory studies of temperature effects on calling song production and recognition in Gryllus firmus. AB - Temperature effects on calling song production and recognition were investigated in the North American field cricket, Gryllus firmus. Temporal parameters of field recorded G. firmus calling song are strongly affected by temperature. Chirp rate and syllable rate increase, by factors of 4 and 2, respectively, as linear functions of temperature over the range in which these animals sing in the field (12 degrees-30 degrees C). Temperature affects syllable duration to a lesser extent, and does not influence calling song carrier frequency. Female phonotactic preference, measured on a spherical treadmill in the laboratory, also changes with temperature such that warmer females prefer songs with faster chirp and syllable rates. Best phonotaxis, measured as accuracy of orientation to the sound source, and highest walking velocity, occur in response to temperature-matched songs at 15 degrees, 21 degrees, and 30 degrees C. Experiments under semi-natural conditions in an outdoor arena revealed that females perform phonotaxis at temperatures as low as 13 degrees C. Taken together, the song and phonotaxis data demonstrate that this communication system is temperature coupled. A strategy is outlined by which temperature coupling may be exploited to test hypotheses about the organization of neural networks subserving song recognition. PMID- 1403993 TI - Temperature coupling in cricket acoustic communication. II. Localization of temperature effects on song production and recognition networks in Gryllus firmus. AB - Acoustic communication in Gryllus firmus is temperature-coupled: temperature induces parallel changes in male calling song temporal pattern, and in female preference for song. Temperature effects on song production and recognition networks were localized by selectively warming head or thorax or both head and thorax of intact crickets, then eliciting aggression song production (males) or phonotaxis to synthetic calling song (females). Because male song is produced by a thoracic central pattern generator (CPG), and because head ganglia are necessary for female song recognition, measurements of female phonotaxis under such conditions may be used to test the following competing hypotheses about organization of the song recognition network: 1. A set of neurons homologous to the male song CPG exist in the female, and are used as a template that determines preferred values of song temporal parameters for song pattern recognition (the common neural elements hypothesis), and 2. temporal pattern preference is determined entirely within the head ganglia. Neither selective warming of the head nor of the thorax was effective in changing female song preference, but simultaneous warming of head and thorax shifted preference toward a faster song in most preparations, as did warming the whole animal by raising ambient temperature. These results suggest that phonotactic preference for song temporal pattern is plurisegmentally determined in field crickets. Selective warming experiments during aggression song production in males revealed that syllable period is influenced but not completely determined by thoracic temperature; head temperature is irrelevant. The song CPG appears to receive some rate-setting information from outside the thoracic central nervous system. PMID- 1403994 TI - Evidence for a difference in syntactic knowledge between skilled and less skilled adult readers. AB - In two experiments, we investigated the relationship between reading ability and linguistic knowledge in adults. The results from Experiment 1 showed that good comprehenders performed more accurately than average comprehenders in a syntactic judgment task that required them to decide whether pairs of words served the same grammatical function in sentences. By contrast, the reader groups performed similarly when required to make semantic judgments about whether pairs of words were related in meaning. In Experiment 2, individuals were classified according to comprehension level and reading speed. Good comprehenders again performed more accurately than average comprehenders in the syntactic task but not the semantic task. We argued that differences in form-class knowledge could be associated with corresponding differences in syntactic-processing efficiency, and thus with variation in reading-comprehension skill generally. PMID- 1403995 TI - Bilingualism and cognitive development in relation to threshold theory. AB - A study was conducted to examine the relationship between bilingualism and cognitive development, as predicted by threshold theory. This theory maintains that there may be levels of linguistic proficiency which bilingual children must attain in order to avoid cognitive deficits and to allow the cognitive benefits. On the whole, the results were consistent with the theory, in that an overall bilingual superiority was found only for those children who had attained a high degree of bilingualism. An overall bilingual superiority was not found for those children who had attained lower degrees of bilingualism. These results are discussed further in relation to Bialystok's model. PMID- 1403996 TI - The psychological costs of screening for cancer. AB - The benefits of cancer screening programmes accrue to those who have cancer or identifiable precancerous conditions, and in whom the disease progression is slowed or halted by earlier intervention. The costs accrue to the rest of the population for whom there is no direct benefit to health. Attention has been given to the medical risks of screening procedures and to the economic costs, but there has been very little regard paid to the psychological costs. The aim of this paper is to evaluate the psychological impact of screening. Screening participants who are found to have untreatable disease, or for whom the interventions prove ineffective, have a greater proportion of their life as a cancer patient with all the associated psychological (and perhaps physical) distress, but no increase in their life expectancy. Those who receive false positive results may experience acute psychological distress produced by the prospect of a grave diagnosis before they are found to be free from serious disease. Even the procedure of screening itself, with the disturbance of the invitation, the discomfort of the tests and the wait for the diagnosis, can have a significant impact upon some patients. This paper evaluates the psychological costs which may be involved across the whole screening procedure, from the possible alarm of receiving an invitation to participate in screening, to the trauma of a cancer diagnosis for someone who had been unaware of any symptoms. PMID- 1403997 TI - The relationship of parenting styles and social competency to Type A behavior in children. AB - This study examined parenting styles, Type A behavior in parents and children, and social competence in children. Fifty 1st-6th grade children, parents, and their teachers participated. Type A behavior in parents was associated with a controlling style of parenting, but not with pressuring the child to achieve. Parenting styles of achievement pressure and high control were related to impatient and aggressive behaviors in children, as measured by the MYTH, a teacher-scored Type A behavior instrument. In addition, impatience and aggressiveness in the children were negatively correlated with the child's social competency and ability to function in school. Parenting practices, Type A behavior, and social competency in children may play important roles in the origins of detrimental components of Type A behavior, such as impatience and aggression. PMID- 1403998 TI - Active coping style is associated with natural killer cell cytotoxicity in asymptomatic HIV-1 seropositive homosexual men. AB - The aim of this study was to examine the hypothesis that a psychosocial model was associated with natural killer cell cytotoxicity (NKCC) in HIV-1 infection. A sample of 62 HIV-1 seropositive homosexual men at CDC stages II and III were given a psychosocial battery assessing life stressors, social support, and coping style. A regression model quantifying these variables along with control variables for alcohol use, substance use and nutritional status was estimated. Active coping style was directly and positively associated with NKCC, and trends toward a negative relationship of life stressors and a buffering effect of social support on lives stressors were also observed. The results suggest that (1) control variables should be included with psychosocial models and that (2) psychosocial factors, especially active coping, may have a deterrent effect on loss of NK cell function. Active coping style may merit a specific focus in future research of life stressors and the immune system. PMID- 1403999 TI - Couple therapy improves mental well-being in chronic low back pain patients. A controlled, five year follow-up study. AB - Fifty-six chronic low back pain (CLBP) patients participated in a controlled, prospective 5-yr follow-up study evaluating the long-term effects of five-session couple therapy. Twenty-eight patients were included both in the treatment group and in the control group. Outcome measures were self-reported psychological distress, marital satisfaction, health locus of control, pain and disability as well as clinical examinations. The reliability of the outcome measures was statistically analysed and found acceptable. At the 5-yr follow-up assessments, psychological distress was found to be decreased in the treatment group and increased in controls. The difference between the groups was significant. No difference was found in the other self-reported or clinical outcome measures. We conclude that couple therapy has a prolonged beneficial effect on the mental well being of CLBP patients. PMID- 1404000 TI - Participation in physical activity and cardiovascular fitness have different effects on mental health and mood. AB - The cardiovascular fitness, blood pressure, resting pulse, lung capacity and body fat of 246 subjects were measured and each subject completed activity, mental health and mood questionnaires. The results of this study support the hypothesis that participation in physical activity, rather than cardiovascular fitness, is the factor associated with better mental health and mood. Higher levels of physical activity were associated with better mood scores unless the individuals were unfit. This research has implications for how physical activity is prescribed; the emphasis needs to be on performing physical activity rather than improving fitness and should not be beyond the physical capabilities of the individual. PMID- 1404001 TI - Factors associated with psychological help-seeking in HIV disease. AB - The study was aimed at evaluating the psychosocial and psychopathological characteristics of individuals with Human Immunodeficiency Virus (HIV) infection seeking psychological help compared with a sample not seeking help. Two hundred and seventy-one HIV seropositive (HIV+ve) subjects belonging to three transmission categories (90 gay men, 154 intravenous drug users and 27 heterosexuals) who were assessed at their first clinic appointment and offered access to psychological help were studied. Subsequently, it was found that 45 (17%) took advantage of the offer of psychological help, and attended a specialist clinic, while 226 (83%) did not seek help. Stepwise logistic regression analysis was used to establish the characteristics of subjects who received psychological help. Results showed that five factors identified at the time of first clinic appointment were significantly associated with seeking psychological help subsequently: (1) having a current DSM-III-R Axis I psychiatric diagnosis; (2) being single; (3) belief of being affected by a serious physical illness (negative correlation); (4) higher level of education; and (5) no past or current history of substance misuse. The implications of the findings are discussed. PMID- 1404002 TI - Glossodynia--psychodynamic basis and results of psychopathometric investigations. AB - Between 1985 and 1988, 131 patients suffering from glossodynia were submitted to a careful examination that included a neurological work-up, a detailed psychiatric interview and a number of psychological tests. Particular attention was paid to psychosomatic and psychopathologic disorders. The average age of the patients was 55 yr, and 73% of them were female. In 40% of patients, the psychiatric interview revealed no psychopathological findings, while in most of them, a psychiatrically relevant disorder, usually depression, was found. All patients had an unremarkable neurological status, and the EEG's showed no pathological changes. Psychodynamic considerations in conjunction with the elevated scores for depressive mood, anxiety and tension suggest that glossodynia is an expression of a psychosomatic disorder. PMID- 1404003 TI - Validity and reliability of the Toronto Alexithymia Scale (TAS) in a population study. AB - Alexithymia refers to the difficulties an individual has to experience and express his feelings. Various self-report questionnaires have been introduced to measure alexithymia, but only a few rigorous validity studies of this concept have been carried out in nonclinical populations. The aim of this study was to evaluate the psychometric properties of the Toronto Alexithymia Scale (TAS) in a population sample of 1560 middle-aged men from eastern Finland. The modified version of the TAS applied in this study had a factor structure that matched the previous results and the theoretical concept of alexithymia. Internal consistency of the total TAS scale, as well as the 8 month retest reliability, were adequate. The TAS correlated fairly well with an interview-based evaluation of alexithymic features. The results suggest that the TAS could be a useful screening instrument for alexithymic features in a population study, but the scale would probably need some revisions. PMID- 1404004 TI - The stress of marriage to an alcoholic. AB - 1. Historically, wives of alcoholics have been described as having disturbed, pathological personalities that were instrumental in causing and maintaining their husbands' drinking. More recently, researchers have tended to support the view that the behavior of these women reflects their stressful circumstances. 2. The women in the study reported interpersonal, extrapersonal, and intrapersonal stressors. The most frequently reported and highest ranked stressor was their relationships with their husbands. 3. Sobriety does not necessarily mean that stressors disappear. 4. More research is needed for nurses to have the knowledge necessary to help wives of alcoholics to cope with their stressors. PMID- 1404005 TI - Disruptive, institutionalized elderly: a cost-effective intervention. AB - 1. Psychomotor agitation can be decreased without the use of physical or chemical restraints. 2. A structured activity program can be integrated into the treatment plan of disruptive patients. 3. Nurses working in long-term care settings are in positions to be advocates for change. PMID- 1404007 TI - Psychiatric nurses' attitudes toward and involvement in nursing research. AB - 1. The three major blocks to clinical nursing research are lack of time, knowledge, and administrative support. 2. Positive attitudes toward nursing research were found to be related to nurses' advanced levels of education. 3. Two strategies to foster the development of research skills are inservice education classes and individualized guided learning experiences. 4. Two essential resources for staff who are expected to engage in clinical research activities are statistical consultation and clerical services. PMID- 1404006 TI - The neglected elder: a family systems approach. AB - Abuse and neglect of older adults is largely an invisible problem. Those who are vulnerable are often hidden from the public eye. Troubled families characteristically maintain an isolated existence and, therefore, the mistreatment of elders can occur without the knowledge of neighbors or interested community members. Factors that operate to keep the problem hidden include society's emphasis on family privacy, the victim's unwillingness or inability to report the problem, stereotypes about the aged, and denial (Quinn, 1986). Although the problem of abuse and neglect of elders is not as prevalent as child maltreatment, it is a significant societal problem in need of increased public awareness. This article will focus on the treatment of elder neglect within the context of the family. PMID- 1404008 TI - Medication management, antidepressant drugs, and the elderly: an overview. AB - 1. Several factors may affect an elderly client's use of medications: polypharmacy, potentially leading to interactions; over-the-counter drugs taken without a physician's knowledge; noncompliance or poor compliance with medication regimens; and ageist beliefs. 2. Psychiatric nurses must be aware that the signs and symptoms they observe may be the result of normal physical or biological aging, psychosocial changes, disease-related changes, medication side effects, or a drug interaction. 3. Nurses must ask two questions when psychotropic drugs are used with elderly clients: What will be the onset, duration, magnitude, and characteristic action of a specific drug in an individual; and What are the characteristics of an "ideal" medication? PMID- 1404009 TI - Manual eases home care for patients with HIV/AIDS. PMID- 1404010 TI - Maintaining identity in elderly couples with chronic illness. AB - With the onset of chronic illness, it has been necessary for these couples to evaluate and redefine their separate as well as merged identities. As each of these individuals sought to realize a mature identity, role adjustments were required. Although not every member of the two illustrated couples had been able to accept the effects and concurrent responsibilities of chronic illness, the nurse practitioner was in a unique position to provide guidance. By reinforcing the importance of healthy identity states, these clients were able to merge temporarily and respond to their partner's basic needs, exchanging a sense of mutual satisfaction, and then to separate into distinct individual identity states. A major task of the older adult is to re-evaluate identity in light of the roles currently being played in life. Through this process, a workable philosophy of life and death should evolve. Most older people engage in a life review of accomplishments and failures, seeking to integrate the diverse elements to obtain an acceptable view of their life's worth (Kaluger, 1984). Couples experiencing chronic illness must reconsider the consequences of this illness state to adequately formulate healthy individual and merged identities. The role of the nurse practitioner is essential in providing guidance for adapting to the life changes confronting elderly couples with chronic illness while maintaining healthy individual and merged identities. PMID- 1404011 TI - Assessing geropsychiatric patients. AB - Although other disciplines involved in the care of geriatric patients with psychiatric or neurobehavioral problems have established assessment procedures, this is not the case for nursing. Some approaches to assessing geropsychiatric patients from a nursing perspective have been proposed (Baldwin, 1987; Burnside, 1981; Ninos, 1985), but they have been limited in scope (Abraham, 1990b). However, with nursing assuming an increasingly central role in the multidisciplinary care of geropsychiatric patients and their families, a comprehensive and accepted method of multidimensional geropsychiatric nursing assessment is necessary. This method enables nurses to provide the best possible nursing care to patients and families while contributing effectively to multidisciplinary assessment and intervention. To this end, Abraham and associates (Abraham, 1990a; Thompson-Heisterman, 1992) developed the Psychogeriatric Nursing Assessment Protocol (PNAP). Previous articles have described the rationale and content of the PNAP (Abraham, 1990a; Thompson Heisterman, 1992). This article will draw on the authors' clinical experience in using the PNAP and will offer practical clinical strategies for assessment within the PNAP framework. The PNAP is presented in the Figure, and readers are referred to previous articles for detailed descriptions of the various aspects of the PNAP. A rating form has been developed for use with the PNAP that permits quantification of clinical observations and the determination of selected clinical scores. PMID- 1404012 TI - A portrait of homelessness. AB - The homeless elderly are vulnerable, silent, and fearful. Their trajectory into homelessness more often than not precludes recovery and takes them on a course toward early death or nursing home placement. Psychiatric nurses who work in community or acute care settings are in key positions to recognize elderly victims of homelessness, assess their needs, match them to services, start them on the road to recovery, and become their advocates. The definition of a homeless person as agreed on in the Report of the Federal Task Force on Homelessness and Severe Mental Illness (1992) is the one used in the Stewart B. McKinney Homeless Assistance Act (Public Law 100-77). A homeless person is someone "who lacks a fixed, regular, and adequate nighttime residence" and whose main nighttime residence is a "supervised public or private shelter designed to provide temporary living accommodations; an institution that provides a temporary residence for individuals intended to be institutionalized; or a public or private place not designed for, or ordinarily used as, a regular sleeping accommodation for human beings." This definition, then, excludes those individuals living on the "fringes" in substandard or condemned housing, a condition that warrants attention in general and particularly among the elderly. PMID- 1404013 TI - Staff stress on an Alzheimer's unit. AB - Nurses working with the elderly encounter many complex and potentially stressful care situations. Nowhere is this more true than for nursing home staff who work in highly demanding, labor- and client-intensive jobs. A number of factors contribute to the high levels of stress found among nurses who work with the elderly, including continual exposure to physical and emotional pathology and death, and conflict with families, co-workers, supervisors, and representatives from other departments or professions (Goldin, 1985; Klus, 1980). When the stress level in a long-term care facility becomes overwhelming, role conflict, ambiguity, poor self-esteem, and burnout may ensue (Goldin, 1985; Heine, 1986; Klus, 1980; Morrow-Winn, 1985). The process of burnout is characterized by a progressive loss of idealism, energy, and purpose that eventually leads to emotional overextension and exhaustion (Price, 1984). PMID- 1404014 TI - Abuse among rural mentally ill. AB - Each American adult has the right to make individual decisions. These decisions include preferences in lifestyle, occupation, diet, housing, health-care treatment, and allocations of financial resources. The right to autonomous decision making is not limited to young or middle-aged adults, nor is it limited to those occasions during which the individual has the capacity to personally participate in the decisions (US Congress, 1987). The right also applies to elderly, incapacitated, mentally ill, or dependent adults. Because of this autonomy, no individual must suffer physical, psychological, or financial coercion. Based on these rights, all 50 states have enacted statutes to protect dependent adults and to authorize government intervention in cases of suspected adult abuse (Hunzeker, 1990). Iowa is one of the states that has enacted dependent adult abuse legislation, and in 1988, health-care practitioners in Iowa became mandatory reporters of adult abuse (Iowa Code, 1992). As mandatory reporters, all nurses who treat, counsel, examine, or attend dependent adults must observe the physical status and interpersonal relationships of their clients and significant others to identify potential conflict or injury. Categories of abuse recognized by the Iowa law include physical, sexual, and financial abuse, neglect by self, and neglect by another (Figure). PMID- 1404015 TI - What clinical experiences are needed before entering psychiatric nursing? PMID- 1404016 TI - Chronic pain and depression. AB - Because of the increased incidence of chronic disease and other health problems associated with aging, chronic pain is a common companion for the elderly. Pain is of great clinical importance, often associated with disability, loss of independence, and reduced quality of life. A fact that is of interest to psychiatric nurses is that many elderly with complaints of chronic pain also exhibit signs and symptoms of depressive disorders. Treating chronic pain conditions is complex and difficult, and health-care professionals are increasingly recognizing that psychological factors are often involved in the development and continuation of chronic pain problems. Depression is one of these influential variables. Increased understanding of the role of depression in the etiology and maintenance of chronic pain can improve assessment and intervention for the elderly with chronic pain complaints. PMID- 1404017 TI - Who's for CPR? PMID- 1404018 TI - Allergy: conventional and alternative concepts. Summary of a report of the Royal College of Physicians Committee on Clinical Immunology and Allergy. AB - Allergy is an exaggerated response of the immune system to external substances. It plays a role in a wide range of diseases. In some, such as summer hayfever, the symptoms are entirely due to allergy. In other conditions, particularly asthma, eczema and urticaria, allergy plays a part in some patients but not all. In these situations, allergy may either have a major role or provide just one of many triggers. In an individual patient's illness, the importance of allergy may change with time. The most common allergens (substances causing allergy) are grass and tree pollens, the house dust mite, products from pets and other animals, agents encountered in industry, wasp and bee venom, drugs, and certain foods. Food allergy presents a particularly difficult problem. Some individuals who react to food suffer from true food allergy but in others there is no evidence of an alteration in the immune system. Here the term 'food intolerance' is preferable. Conventional doctors treat allergy by allergen avoidance--where this is possible--and drugs that relieve symptoms. In a few selected cases, in which other methods have failed, immunotherapy (desensitisation or hyposensitisation) is recommended. Patients who consult practitioners of alternative allergy often do so because they are dissatisfied with the conventional approach to diagnosis and treatment, and sometimes because they have conditions which conventional doctors do not accept as having an allergic basis. There is a very wide range of alternative approaches to allergy, including the methods used by clinical ecologists, acupuncturists and homoeopathists. Hypnosis may have a small role to play in asthma, and similar claims for acupuncture need to be evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404019 TI - Can consultants resuscitate? AB - Twenty-four of 53 hospital consultants responded to an offer to attend a resuscitation training course. Fourteen of them had never had resuscitation training. Their performance of basic life-support was assessed before and after training according to the Resuscitation Council UK recommendations. Their initial performance of basic life-support on a manikin was extremely poor. One hour of training and practice resulted in statistically significant improvements. PMID- 1404020 TI - Heart-smart youngsters. The Medicine-Gilliland Fellowship 1991. PMID- 1404021 TI - Vanishing syndromes. AB - Certain syndromes develop because of regression or shrinkage of essential pathways. This account draws attention to six conditions in which different mechanisms and pathways give rise to a scorched-earth policy and to strange clinical syndromes. PMID- 1404022 TI - Diagonal earlobe creases and atheromatous disease: a postmortem study. AB - The association between the grade of earlobe creases and degree of atheromatous disease was investigated in 376 postmortem examinations. Each earlobe crease was individually graded from 0 to 3. The risk of atherosclerosis as a cause of death was nearly doubled in men with grade 3 creases in both earlobes, and more than trebled in women with bilateral high-grade creases. The risk of death from myocardial infarction was 2.50 in men with high-grade creases and 3.70 in women. The earlobe crease is an important sign of atheromatous disease and it may be useful to include it in the clinical examination of patients. PMID- 1404023 TI - Steroid-induced bone disease. Conflicting views of respiratory and bone physicians. AB - Physician members of the Thoracic Society and the Bone and Tooth Society were circularised about their views on the prophylaxis, screening and treatment for steroid osteoporosis. Bone physicians were more active than respiratory physicians in screening and prophylaxis and were more likely to favour bone densitometry in assessment and bisphosphonates in treatment. Further studies are required to establish the value of prophylactic agents in steroid osteoporosis but meanwhile respiratory physicians should appreciate the value of the relatively simple technique of bone densitometry in assessment and consider whether they should be more active in prophylaxis. PMID- 1404024 TI - Guidelines for good practice in and audit of the management of upper gastrointestinal haemorrhage. Report of a joint working group of the British Society of Gastroenterology, the Research Unit of the Royal College of Physicians of London and the Audit Unit of the Royal College of Surgeons of England. PMID- 1404025 TI - Training programmes for medical registrars. How we did it in the West Midlands. PMID- 1404026 TI - Animal welfare--the European dimension. PMID- 1404027 TI - A unifying hypothesis of body fluid volume regulation. The Lilly Lecture 1992. PMID- 1404028 TI - Science and medicine: implications for the future. Based on the Nuffield Lecture 'medicine, science and the arts', at the Royal Society of Medicine on 16 April 1991. PMID- 1404029 TI - A Chinese medical college. PMID- 1404030 TI - Recipe gravitas. PMID- 1404031 TI - Medical education in chaos. PMID- 1404032 TI - The trouble with guidelines. PMID- 1404033 TI - Guidelines and a proposed audit protocol for the initial management of an acute hot joint. PMID- 1404034 TI - An improved 'interim discharge letter'--a successful outcome from audit. PMID- 1404035 TI - Research in training posts. PMID- 1404036 TI - Surgical scoring, risk assessment and the surgeon. PMID- 1404037 TI - Tissue expansion. PMID- 1404038 TI - Breast cancer in Zaria, Nigeria. AB - A retrospective analysis of the clinical records of 129 women with breast cancer seen at the Ahmadu Bello University Teaching Hospital, Zaria has been carried out. The patients were young (median age 38 years), 64% were premenopausal and 89% were parous and had practised prolonged breastfeeding. Patients typically presented with massive breast tumour (median diameter 10 cm) with matted axillary lymph nodes in 57%. Eighty-eight per cent of patients had stage III or IV disease, and in 85% the histological tumour type was infiltrating ductal carcinoma. Mastectomy was the main mode of treatment and the default rate both before and after treatment was high. The median crude survival period for our patients was only 1.5 years. The survival disadvantage is probably the result of the combined effect of delayed presentation by the patients, the preponderance of biologically very aggressive tumours and our grossly limited therapeutic modalities. PMID- 1404039 TI - Use of autologous fibrin glue in the treatment of splenic trauma: an experimental study. AB - There is little doubt that preserving the spleen will contribute to a much more favourable outcome in patients undergoing splenic surgery, as a result of avoiding the well known risks of splenectomy. Among many operative methods described for splenic salvage, application of autologous fibrin glue (AFG) is particularly promising because of its unique characteristics. The use of AFG has been evaluated and its efficacy and tissue compatibility assessed in the treatment of splenic trauma in 15 partially splenectomized New Zealand White rabbits. The application of the AFG to the resected splenic surface achieved complete haemostasis in all animals. The animals were divided into four groups and were killed at varying intervals ranging from 24 h to 10 weeks. During re exploration there was no evidence of recurrent bleeding and histopathological examination revealed progressive absorption of the AFG with a minimal inflammatory response. It is concluded that AFG is an effective haemostatic agent with good systemic and local compatibility and can be used in splenic salvage, which thereby avoids the use of non-autologous products with their risks of disease transmission. PMID- 1404040 TI - Management of pancreatic pseudocyst in childhood: an increasing role for percutaneous external drainage. AB - A total of four patients with a major pancreatic pseudocyst were treated by percutaneous pigtail catheter drainage. All patients recovered with complete resolution of the pseudocyst. There were no complications in relation to catheter insertion. Mean(s.d.) hospital stay was 56(15) days with a mean(s.d.) duration of catheter drainage and total parenteral nutrition of 21(14) and 35(9) days respectively. Percutaneous drainage is an appropriate method of first line therapy for non-resolving or enlarging pancreatic pseudocyst in children. PMID- 1404041 TI - Intestinal malrotation in Trinidad. AB - Fifty-one children under the age of 10 years admitted to a general hospital in Trinidad had a confirmed diagnosis of malrotation of the intestines. This was the primary diagnosis in 20 cases. Analysis of the records of these 20 revealed that one-half were less than 1 month of age at first presentation. Vomiting was a universal complaint, and nearly two-thirds were malnourished. Disturbed bowel habit, anorexia and abdominal pain were also reported. In 30% (six of 20) there were signs of dehydration; an equal number had features of intestinal obstruction. Radiological investigation provided the diagnosis in all but one child, who underwent surgical exploration with a provisional diagnosis of appendicitis. Although a volvulus was found in 35% of cases, no resections were necessary. A high rate of morbidity and a mortality rate of 15% highlight the problems involved in the surgical care of young infants. PMID- 1404042 TI - Pyloromyotomy through circumumbilical incision. AB - Twenty-two infants suffering from infantile hypertrophic pyloric stenosis underwent Ramstedt's pyloromyotomy using circumumbilical incision. There was no difficulty in delivering the pylorus out of the incision. Three patients developed wound infection, one patient developed wound dehiscence at the fascial plane and one patient developed stitch sinus. No incisional hernias were noted after a follow-up period ranging from 2 months to 4 years (mean 27 months). All scars were neat except that of the patient who developed wound dehiscence at the fascial plane and another who developed stitch sinus. This incision is cosmetic and gives access that is almost comparable to other incisions without a significant increase in the morbidity rate. PMID- 1404043 TI - Use of calcium alginate to pack abscess cavities: a controlled clinical trial. AB - Many conventional dressings are painful when removed, and may be detrimental to healing. In a pilot study ten consecutive abscesses, requiring incision and drainage, were packed with a calcium alginate dressing: this was well tolerated, its removal causing minimal pain. No adverse effects were attributable to its use. A controlled trial was therefore carried out to compare calcium alginate with the more traditional saline-soaked gauze for packing abscess cavities, following incision and drainage. Patients were randomized to receive either calcium alginate (16 patients) or gauze dressing (18 patients). At the first dressing change the patient marked on a linear analogue scale the pain experienced; the nurse noted similarly the ease of removal of the dressing. Calcium alginate was significantly less painful to remove after operation (P less than 0.01), and also easier to remove (P less than 0.01) than gauze dressings. If abscess cavities are packed after incision and drainage, calcium alginate appears to be an improvement on conventional dressings. PMID- 1404044 TI - Free microvascular tissue transfer in Newcastle upon Tyne. AB - One hundred and eleven cases of free tissue transfer were reviewed to assess the indications for, and results of, such procedures. More than 90% of cases were seen after treatment of tumour or trauma, with the most utilized flaps being the radial forearm, jejunum and latissimus dorsi. Fifteen per cent of cases required re-exploration of the anastomosis, of which more than 75% were salvaged. Haematoma formation and venous thrombosis were the commonest problems and were more successfully treated than arterial occlusion. The overall success rate was 92%. Free microvascular tissue transfer is a useful and reliable technique, especially in the management of head and neck tumours and limb trauma. The most important factors relating to flap survival are the experience of the surgical team and the integrity of the anastomosis. PMID- 1404045 TI - Percutaneous angioplasty in a district general hospital: impact and implications. AB - Over a 2-year period 147 angioplasties were performed for stenoses or occlusions above or below the inguinal ligament. Most patients had intermittent claudication. The stenosis or occlusion was successfully dilated in 88% of cases. Successful dilatation produced a good result, as determined by improvement in Doppler pressures (63%), an increase in walking distance (60%) or limb salvage (66%). There have been 15 complications. Of seven distal emboli, three required operation and four were successfully treated with intra-arterial streptokinase. In three patients, immediate occlusion of the femoral artery required urgent operation, and one patient died following intra-arterial streptokinase and subsequent angioplasty. There were three further major haematomas, one requiring suture of the puncture site. Had angioplasty not been available, about half of the patients in this series would not have had an angiogram. Many of the remainder, not being suitable for vascular reconstruction, would have been treated conservatively. Thus a new group of patients is being defined for whom interventional treatment is now appropriate, and this has important revenue implications. Percutaneous transluminal angioplasty is a safe and effective technique in carefully selected patients. Complications can occur, however, and the immediate availability of a vascular surgeon is essential. PMID- 1404046 TI - Contractures after burns: some observations from a 3-year review in Zimbabwe. AB - A retrospective study is presented of 53 consecutive patients (25 men, 28 women) with contractures following burns admitted to Mpilo Central Hospital between August 1988 and August 1991. Of the total, 85% were aged 12 years or less. Most of the patients (75%) came from rural areas and in 67% of cases where the nature of the burning agent was known, the burn resulted from an open fire. The site most commonly affected was the hand (51% of cases). Most of the contractures were released either by cross cutting and split skin grafting, or by using some form of flap. No major complications were encountered apart from a few minor wound infections which settled down on antibiotics and dressings. To reduce the incidence of contractures in our practice it is important to educate the rural community about the dangers of open fires especially to children. Rural health personnel should be encouraged to consider early referral of patients with burns likely to lead to contracture formation. PMID- 1404047 TI - Evaluation of a new non-woven theatre swab. AB - A new non-woven theatre swab was compared with traditional gauze in laboratory and clinical studies. Results of both clinical and laboratory-based studies showed the non-woven swab to be as effective as traditional gauze in terms of softness, conformability, ability to pad or pack, resistance to snagging and shredding, and ease of counting when wet. The non-woven swabs were also superior to gauze with regard to their ability to retain fluid. Manufactured from polyester and hemisynthetic viscose, the non-woven swabs can be produced to a uniform standard and are less expensive. It is concluded that the new non-woven material has practical and economic advantages over traditional gauze. PMID- 1404048 TI - Gastric volvulus caused by giant ovarian cyst. PMID- 1404049 TI - Jejunal diverticulum in a child presenting with small bowel obstruction. PMID- 1404050 TI - Mallet finger: long-term review of 100 cases. AB - One hundred cases of mallet finger are reviewed to assess the significance of the results of treatment. This study revealed that the mallet fingers with chip fractures and those without fractures showed satisfactory results in 85% of cases in the long term (32 months) with conservative treatment. Even though there was a statistically significant difference between the satisfied and unsatisfied patients in extensor lag (P less than 0.0001), arc of movement (P greater than 0.001) and pinch grip (P greater than 0.001), none of these patients was willing to undergo surgery to improve their fingers. PMID- 1404051 TI - Comminuted Colles' fractures: a prospective trial of management. AB - Patients suffering from comminuted fractures of the lower end of the radius were treated by one of two protocols and followed for 6 months. One group was treated by a regime of percutaneous wiring based on the technique described by DePalma. This was compared with the results obtained from the conventional treatment of manipulation and application of plaster of Paris for similar injuries. Final function was found to be closely related to anatomical results and this was obtained earlier and with greater predictability in the wired group. There were statistically significant differences between the two groups at 6 months in extension (P less than 0.001), ulnar deviation (P greater than 0.05), grip strength (P less than 0.001), radial angle (P less than 0.0001), radial length (P less than 0.0001), and dorsal/volar angle (P greater than 0.0001). Using a modified McBride's system of scoring, the results were found to be directly correlated to the anatomical findings at the end of 6 months. PMID- 1404052 TI - Controlled prospective trial of wound management in elective hand surgery. AB - A total of 33 consecutive patients undergoing elective hand operations were randomly allocated 5 days after the operation either to have all dressings discarded or to continue with an occlusive bandage for a further 2 weeks. Assessments at 2 and 6 weeks showed that wound healing, hand function, symptoms and complications were identical in both groups. It was concluded that for selected patients early removal of hand dressings after surgery does not have any deleterious effects. PMID- 1404053 TI - Elbow fat pad sign: implications for clinical management. AB - The significance of the radiological fat pad sign indicating elbow joint effusion after trauma when a fracture is not visible remains controversial. This retrospective analysis of 45 cases examines the need for routine repeat radiography at 2-week review. At follow-up, 29 had normal repeat radiographs, two had undisplaced radial head fractures, three had no radiographs but were clinically well and 11 failed to attend. The incidence of fracture in those having repeat radiography was 6%. We conclude that routine repeat radiography is unnecessary. PMID- 1404054 TI - Aspiration cytology of the breast with immediate reporting: initial experience with 1000 patients in a district general hospital. PMID- 1404055 TI - Assessment of the reliability of the symptoms and signs of acute appendicitis. PMID- 1404056 TI - Casualty officers under-estimate the blood loss from fractures. PMID- 1404057 TI - Assessment of the reliability of the symptoms and signs of acute appendicitis. PMID- 1404058 TI - Assessment of the reliability of the symptoms and signs of acute appendicitis. PMID- 1404059 TI - Radon concentration in two largest cities in semitropical Taiwan. AB - Grab sampling either using the active charcoal method in combination with an ionization chamber or using a working level monitor was performed for the measurement of radon concentration in Taiwan's two largest cities Taipei and Kaohsiung. Long-term monitoring of radon concentration in dwellings and business buildings was also carried out with cellulose nitrate films as the alpha detectors. The average indoor radon concentration in these two cities is 17 +/- 6 Bq m-3. The outdoor radon concentration is about one-half of that on average. As assessed according to the model of UNSCEAR 1988, the induced effective dose equivalent is 0.67 mSv y-1. Radon concentration in coal mines showed an average of 88.5 +/- 9.5 Bq m-3. PMID- 1404060 TI - Concentrations of radionuclides of size fractionated fly-ash emissions from a thermal power plant using Taiwan coal. AB - Coal, fly ash and bottom ash samples were taken from a 300-MWe coal-fired power plant with a daily coal consumption of 2400 tons. A high volume sampler coupled with several mesh testing sieves was used to separate fly ash samples into different size fractions. Determination of the concentrations of 40K, 238U, 226Ra, 210Pb, 210Po, 228Th and 228Ra was carried out either by gamma or alpha spectrometry. For elements volatilized during combustion, their radionuclide concentrations decrease with increasing particle size. The enrichment factors for all radionuclides mentioned above were studied. Their values range from 31.0 for 210Po to 2.2 for 228Ra. Of all radionuclides studied, 210Po and 210Pb are the most volatile elements; therefore, an increase in the natural radiation level should first be indicated by an increase in these two nuclides. PMID- 1404061 TI - Specific activities of 60Co and 152Eu in samples collected from the Atomic-Bomb Dome in Hiroshima. AB - Neutron-induced activities 60Co and 152Eu have been measured for samples collected from the Atomic-Bomb Dome locating at 161 m from the hypocenter of the Hiroshima Bomb. Specific activities 60Co/Co and 152Eu/Eu at the time of the detonation have been determined as 10.0 +/- 1.0 Bq mg-1 (steel sample S4) and 80 +/- 9 Bq mg-1 (granite sample G1), respectively. Detailed measurements of 60Co and 152Eu activities for samples collected from various locations of the Dome show almost no directional dependence whether the sample faced to the epicenter or not, nor vertical height dependence between 17 m height and the ground level. In addition, 152Eu was not detected in the sample collected from the basement. It has been shown that the present 60Co activity value, the nearest steel one to the hypocenter, as well as other short distance data are systematically lower than the calculated values based on the neutron fluence of the DS86. PMID- 1404062 TI - Characterization through a data display of the different cellular responses in X irradiated small intestine. AB - Previous work on small intestinal radiation injury has reported changes in epithelial and non-epithelial tissues, but with few quantitative comparisons of different responses by individual cell types. The approach used here quantifies the responses of mouse duodenum to X-irradiation with 6 Gy, 10 Gy and 20 Gy, sampled three days after treatment, and 10 Gy sampled 6 hours, 1 day and 3 days after treatment. Tissue area measurements and counts per circumference for 13 different structural elements are subjected to statistical tests. New data reported here for X-irradiation include the fact that cryptal cells do not respond uniformly, indicating that the crypt/microcolony cannot always be used as a standard unit in assessing radiation injury. Non-epithelial structures, such as submucosal arterioles, are also affected. The data display also includes control referenced ratios, from which are calculated Tissue Indices and a final Morphological Index, which estimates total structural damage. The Indices are useful in drawing attention to unexpected changes in extent or range of data sets. In addition, the Epithelial Index appears to be a sensitive indicator of radiation damage, even at low doses and early time points. The data display includes a graph of the total Indices and summary tables of data, and encourages close study of the constituent data points. PMID- 1404063 TI - Time course of histomorphometric alterations in nerve grafts without connection to a muscle target organ: an experimental study in sheep. AB - In 15 adult sheep, the saphenous nerve (28 +/- 1.8 cm) was used for ipsilateral or for cross-nerve grafting and was sutured to the proximal stump of the cut, motor-nerve branch of the vastus muscle. The distal end of the nerve graft was left without a target organ. Semi-thin cross sections of normal vastus nerves and saphenous grafts and of the distal ends of the grafts were analyzed by computer assisted planimetry, 3, 6, 9, 12, and 18 months after the nerve-grafting procedure. Electronmicroscopy was also performed on specimens from the distal ends of the nerve grafts. Comparing the total number of myelinated nerve fibers in the distal end of the graft, the ipsilateral group showed an increase with time elapsed since nerve grafting, while the cross-over group showed a maximum after 3 and 6 months, and fewer fibers after longer periods of regeneration. Independent of the time passed since nerve grafting, the diameters of the myelinated nerve fibers were homogeneously thin in both experimental groups. Most interesting, the cross-nerve grafts did more poorly than the ipsilateral ones, even before they were influenced by the target muscle. With ultrastructural investigation, the ends of the grafts containing only a few myelinated fibers also showed a low number of unmyelinated fibers, but an increase of collagen fibers. The results have consequences for the clinical application of cross-nerve grafting. PMID- 1404064 TI - Nasal reconstruction with a thin, free flap prefabricated with a silicone sheet: case report. AB - When the reconstruction of facial tissue requires the use of a flap, this is best carried out with a thin flap that matches the texture of facial skin. For this reason, the authors often use postauricular and subclavicular donor sites. In the reported case, a prefabricated flap was created in the patient's subclavicular skin, by utilizing a silicone sheet and transferring the thoracodorsal vessels. Two weeks after the procedure, this prefabricated flap was transplanted with microsurgical techniques, to reconstruct the ala nasi, after a limited resection of a cavernous hemangioma that preserved the alar cartilage. A very favorable outcome was achieved. PMID- 1404065 TI - Vessel pathology and its clinical significance in toe transfer. AB - One hundred cases of toe transfer were subjected to histopathologic vessel examination. Results indicated that vascular injuries are crucially responsible for perioperative and postoperative crisis. A thorough resection of the abnormal vessel segment can prevent circulatory crisis and elevate the survival rate. PMID- 1404066 TI - Aneurysms of the palmar arch and a proper digital artery: case report and literature review. AB - The first reported case of multiple aneurysms of both the palmar arch and a proper digital artery is described. A palmar arch aneurysm was excised, and two end-to-end anastomoses were necessary to restore the blood flow. Microsurgical repair was the only possible treatment in this case. The authors believe that the vascular anatomy should always be restored as naturally as possible. No treatment was necessary for the more distal aneurysms. PMID- 1404067 TI - A technique for the treatment of neuroma in-continuity. AB - A surgical technique for the management of a neuroma in-continuity, in which motor function is preserved and sensory function is reconstructed with nerve grafting, is presented. Tedious and potentially damaging dissection within the neuroma in-continuity is avoided. The functioning motor fascicles are identified proximal and distal to the injury site with electrical nerve stimulation eliciting muscle contraction. These motor fascicles are preserved. The electrically silent and nonfunctioning sensory fascicles are divided proximal and distal to the neuroma and reconstructed with autogenous nerve grafts. These nerve grafts bypass the functioning motor portion of the neuroma in-continuity. PMID- 1404068 TI - An experimental study of ischemia following subcutaneous heterotopic intestinal graft: influence of arterial or venous occlusion. AB - A subcutaneously transferred intestinal model was prepared in the rat and experimental observations were conducted of serial histologic changes in the intestine and of acceptance rates, when the artery or vein in the pedicle was ligated at various times after transfer. Results showed 50 percent take in the artery-ligated group and 12.5 percent in the vein-ligated group, when performed 5 days after transfer; 87.5 percent take in the artery-ligated group and 50 percent in the vein-ligated group, when performed 7 days after transfer; and 100 percent take for both groups, when ligation was performed 14 days after transfer. Consequently, it was concluded that venous occlusion constitutes a greater danger to successful transfer of intestine than arterial occlusion. PMID- 1404069 TI - Recovery after delayed nerve repair: influence of a pharmacologic adjunct in a primate model. AB - Inhibition of calpains in skeletal muscle by the tripeptide, leupeptin, after median-nerve transection in the mid-forearm and a delayed nerve repair of 3-weeks duration, was studied in a primate (Cebus apella) model. Results indicated that leupeptin facilitates axon regrowth and neuromuscular recovery after delayed nerve repair. Toxicologic testing showed that leupeptin, administered at 18 mg/kg intramuscularly, twice daily for 24 weeks after delayed nerve repair, did not adversely affect hematology, clotting, blood chemistry, or echocardiogram profiles. These data indicate that leupeptin is an effective and safe adjunct to delayed nerve repair. PMID- 1404070 TI - Utilization in Alberta's universal dental plan for the elderly, 1974-91. AB - Since 1973 the government of Alberta, a Canadian province of 2.4 million people, has funded a dental care plan for all residents over 64 years old and their dependents. It is the only dental plan in North America that covers all seniors and their dependents residing in a state or province. Under this plan, just over 270,000 persons (in 1990-91) are eligible for comprehensive, premium-free dental services provided by dentists and denturists in private practice on a fee-for service basis. The plan's design, administration, utilization, and costs are reviewed. Utilization increased from 27 percent of eligibles using the plan in 1974-75 to 44 percent in 1990-91, and the mean number of services per user rose from 4.9 to 6.9 during the same time period. Although the cost per eligible person has increased about 200 percent, from Canadian (C) $42 to C $131, these costs only began to exceed the rate of inflation in 1986-87. Even though just 12 percent of the two main providers participating in the plan are denturists, nearly 22 percent of plan patients attended denturists rather than dentists for their complete dentures. Fees paid to dentists by the plan have decreased over time relative to the standard fees for the various services listed annually in the Alberta Dental Association fee guide. The apparent growth of direct additional billing by dentists of plan users to recover the difference between their usual fees and those paid by the plan and the effects of greater plan utilization are discussed, as are future potential difficulties in the plan's administration. PMID- 1404071 TI - Assessing dental practice quality by evaluating radiology items. AB - The DEMCAD dental office assessment instrument was developed to evaluate practice quality using Donebedian's quality assessment model of structure, process, and outcome. This previously validated instrument takes about six hours to complete. Subsequent analysis was undertaken to determine whether an abbreviated office assessment based on the evaluation of radiology items was sufficiently sensitive, specific, and practical to be used as a screening instrument for identifying dental offices with very low evaluation scores. Data for this analysis were obtained from 300 volunteer general dental practices evaluated in the field testing of the DEMCAD instrument. The nine radiology structure items predicted very poorly the overall structure scores. However, 13 radiology process items predicted overall process scores quite accurately. Four of the 13 radiology process items (periodontal diagnoses recorded, interdental bone shown on x-rays, caries diagnoses recorded, and current x-rays mounted) produced a combined R2 of .58. These four radiology variables predicted the 10 percent of the dental practices with the lowest overall process score with 87 percent sensitivity and 93 percent specificity. This analysis showed that an abbreviated dental practice process quality assessment using oral radiology items in an audit of patients' records may be feasible as a screening test for dental office assessment. PMID- 1404072 TI - Smokeless tobacco habits and oral mucosal lesions in dental patients. AB - As part of a smokeless tobacco (ST) intervention study, we collected data on tobacco use habits and oral health for 245 male ST users aged 15 to 77. The study sample was identified during routine dental office visits and represents a relatively diverse population of patients. Oral health data collection included grading the clinical appearance of oral mucosal lesions using Greer and Poulson's classification system, as well as identifying and recording the primary anatomic location of ST placement. Results show that 78.6 percent of ST users had observable oral lesions, 23.6 percent of which were in the most clinically advanced category (degree III). Of the lesions noted, 85 percent were in the same location the patient identified as his primary area of smokeless tobacco placement. In a comparison sample of 223 non-ST-users with the same age distribution, only 6.3 percent had observable lesions. A multiple logistic regression model for ST users showed that lesion presence and severity were most significantly related to current frequency of ST use. PMID- 1404073 TI - Eligible veterans' choice between VA-covered and non-VA-covered dental care. AB - Veterans who were eligible for dental care in Department of Veterans Affairs (VA) facilities at no monetary cost responded to a mailed questionnaire. Seventy-one percent were aware that they were actually eligible for VA dental care. However, only 48 percent reported the VA as their only or primary source of dental care. Eligibility status, perceived quality of VA dental care, use of VA medical care, perception that one's income meets expenses, and perceived need for dental care were significant correlates of using the VA as one's current source of dental care. Level of formal education, perception that one's income meets expenses, transportation pattern, geographic distance from a VA facility, and eligibility status were significant correlates of using the VA as one's current medical care source. Research on VA utilization offers the opportunity to study issues of access to, and use of, a large public health care system whose patients largely receive care at no monetary cost. Veterans' use of VA dental and medical care is apparently influenced by a wide variety of factors, ranging from barriers to access to non-VA systems, to characteristics of the VA delivery system itself, to need for treatment. PMID- 1404074 TI - Fluoride concentrations in human and rat bone. AB - The most recent report on fluoride concentrations ([F]) in human bone was published over a decade ago. Such data are of interest in the context of changing patterns in systemic fluoride exposure. In the study reported here, bone samples were collected from 24 human subjects who underwent orthopedic surgery. Medical histories and the best possible life-time systemic fluoride exposure information were obtained from each subject. Bone samples were assayed for fluoride concentration using the acid diffusion, ion selective electrode method. For ash from whole bone, the lowest value was 378 ppm in a 16-year-old subject, and the highest value was 3,708 ppm in a 79-year-old person. Fluoride concentrations in bone were significantly correlated with age (r = .62). The regression line intercept at birth was 442 ppm, and the slope was 22 ppm per year. When measured separately, trabecular bone ash fluoride concentrations were significantly higher than the corresponding cortical bone values. Trabecular and cortical bone samples from rats' drinking water containing 75 ppm F were assayed for F. The mean trabecular bone fluoride concentration was significantly higher than the mean cortical bone concentration. There was close agreement between F assay results using a modification of the acid diffusion method and the method originally reported by Singer and Armstrong. The human bone ash [F] values reported in this study are similar to those reported from other North American subjects over the last three decades. These findings are of interest in the context of evidence indicating increased systemic fluoride exposure in the United States population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404075 TI - A review of methods to forecast restorative treatment needs. AB - Decision makers in the areas of health policy, resource allocation, and manpower requirements rely implicitly on estimations of treatment needs on which to base their forecasts. The less specific the treatment-need estimate, the less precise the forecast. In previous decades, high caries rates were so prevalent that the dental profession could risk having inexact projections because overwhelming need and demand existed. However, rampant decay is no longer a common occurrence. Decay levels are declining in our nation's children and adults have fewer missing teeth. Therefore, restorative treatment needs and patterns in adult populations are transforming at a time when health care costs are spiraling and budget analysts at all levels of government are questioning the priority of continued support of dental care, dental education, and dental research at current levels. The purpose of this review is to present the existing methods of forecasting restorative treatment needs and to postulate the development of a new method based on the collective experiences of practicing dentists nationwide, an empirical method, to convert surface-specific oral health status data to restorative treatment need information. Need estimations based on empirical data would more accurately reflect the actual distribution of services that practicing dentists provide. PMID- 1404076 TI - Community dental health for Central America: an alternative model for health care delivery in the Third World. PMID- 1404077 TI - Mercury in dental amalgam--a public health concern? AB - Dental amalgam has been the subject of intermittent controversy since it was introduced into dental practice approximately 150 years ago. The controversy has centered on the use of mercury in dental amalgam and the potential health implications to dental patients and dental health professionals from mercury exposure. In recent years the debate over the use of dental amalgam has intensified due to several articles in professional journals and media coverage by television and the press. This paper reviews the recent literature regarding dental amalgam, describes the activities of the antiamalgamists, examines the alternatives to dental amalgam, and reviews the recommendations for additional research. The existing scientific evidence does not demonstrate that mercury in dental amalgam poses a public health hazard. However, researchers on both sides of the controversy agree that much remains to be examined about the health implications of dental amalgam and that the subject merits continued research. PMID- 1404078 TI - The development and practice of social dentistry in Germany. AB - The traditions of social dentistry in Germany represent early forms of dental public health development. It was promoted in dental care facilities where salaried dentists delivered services to target groups, i.e., schoolchildren and sickness fund members. They enabled larger numbers of patients to receive dental care, especially those of lower class origin who otherwise would have remained untreated because of lack of financial resources or scarcity of manpower. School dental clinics not only delivered dental treatment, but also distributed oral hygiene and nutritional information to school-aged children. Social dentistry in the prefluoride era in Germany pursued an egalitarian and social-class oriented concept of dental care delivery, aiming at compensating the detrimental effects that the private practice-based, fee-for-service financed dental care system had produced in the lower classes of the population. The impact of the Nazi regime nearly abolished the institutions of social dentistry. They never were restored in West Germany after World War II. In East Germany dental care had been organized according to traditions of social dentistry, i.e., delivering services in dental treatment centers. Since the unification of the two German states, the institutions of dental care delivery in former East Germany have been restructured to fit the private practice-based model of former West Germany, eliminating most of the social dentistry institutions in the country. PMID- 1404079 TI - Forging policy in the eye of the storm. PMID- 1404080 TI - Role of fluid from seminal vesicles and coagulating glands in sperm transport into the uterus and fertility in rats. AB - The relationship between the quantity of seminal vesicle secretion in the ejaculate, the percentage of spermatozoa reaching the uterus and fertility was studied in rats. Different portions of seminal vesicles were removed from male rats; 15 min after coitus (day 0), the numbers of spermatozoa in the uterus and vagina were counted and the vaginal plug characteristics were noted. Fertility was evaluated by the number of fetuses on day 14. A gradual decrease in the percentage of spermatozoa in the uterus was positively related to the reduction in seminal vesicle secretion, estimated by plug weight. This decline was not caused by a delay in sperm transport to the uterine lumen and the results suggested that the spermatozoa that fail to enter the uterus in the first minutes after coitus never enter. The vaginal plug weight, which is related to the seminal vesicle weight, and the position of the plug, which must be firmly lodged into the cervical opening, seem to be the most important conditions for promoting the rapid passage of spermatozoa into the uterus. When the seminal vesicles were partially removed, the plug was not tightly lodged and formed a 'cup' filled with spermatozoa. The number of fetuses did not show a close correlation with the quantity of seminal vesicle secretion. Studies of males in which the seminal vesicles had been removed indicated that a normal number of fetuses can be obtained despite low numbers of spermatozoa reaching the uterus. Ablation of the coagulating glands showed that, when there is no vaginal plug, no spermatozoa reach the uterus and fertility is suppressed. Nevertheless, the complete removal of coagulating glands is difficult; when small portions of these glands remain, the vaginal plug is formed and then fertility is achieved. PMID- 1404081 TI - Release of two-cell block by reduction of protein disulfide with thioredoxin from Escherichia coli in mice. AB - The development of mouse pronuclear-stage embryos in media containing various concentrations of thioredoxin was monitored and the influence of antithioredoxin immunoglobulin G (IgG) and heat-treated thioredoxin on the thioredoxin-induced effects was evaluated. A significant increase in the number of four-cell embryos (76.3%) and blastocysts (37.3%) was observed when embryos were cultured in the medium containing 50 micrograms thioredoxin ml-1 compared with the rates (55.8 and 3.8%, respectively) in the basic medium. The number of blastocysts increased significantly to a maximum of 70.2% at 500 micrograms ml-1. The biological activity of thioredoxin was evident after dialysis, but was markedly impaired by the addition of anti-thioredoxin IgG to the culture medium. Treatment at 60 degrees C for 5 min did not affect the enzymatic and biological activity of thioredoxin. More severe heat treatment (121 degrees C for 30 min) attenuated the enzymatic activity to 40% of its initial value and reduced the biological activity (number of blastocysts, from 77.8 to 51.6%). These results indicate that the effect of thioredoxin on the two-cell block is due to the thioredoxin molecule itself, and suggest that disulfide formation within or between proteins resulting from oxidative stress is one of the major causes of the two-cell block. PMID- 1404082 TI - Maintenance or stimulation of steroidogenic enzymes and testosterone production in rat Leydig cells by continuous and pulsatile infusions of luteinizing hormone during passive immunization against gonadotrophin-releasing hormone. AB - The importance of the pulsatility of luteinizing hormone (LH) secretion in maintaining key enzymes in the testosterone biosynthetic pathway in Leydig cells was studied using rats in which LH secretion was suppressed by passive immunization against gonadotropin-releasing hormone (GnRH) and replaced by continuous or pulsatile i.v. infusions of exogenous LH, all delivering the same daily dose of the hormone (300 ng per 100 g NIDDK-ovine LH-24). Continuous infusions (12.5 ng per 100 g h-1) were compared with infusions of 1 min pulses every 2 h (25 ng per 100 g) and every 4 h (50 ng per 100 g). After 5 days of treatment in vivo with sheep anti-GnRH serum (or normal sheep serum) and LH (or vehicle), Leydig cells were purified and assayed in vitro for maximum production of testosterone stimulated by human chorionic gonadotrophin (hCG) and supported by 25-hydroxycholesterol and for the activities of cholesterol side-chain cleavage, delta 5-3 beta-hydroxysteroid dehydrogenase-delta 5-4-isomerase (3 beta HSD-isomerase) and 17 alpha-hydroxylase. Relative contents of cholesterol side chain cleavage and 17 alpha-hydroxylase were also quantified by western and immunoblotting analysis. Activity of 3 beta-HSD-isomerase was reduced by about 40% by anti-GnRH treatment and was increased by all LH regimens in anti-GnRH treated animals, with no consistent pattern in the effects of the different LH regimens. Results for testosterone-producing capacity and the other two enzymes differed in several respects. Treatment with anti-GnRH serum markedly reduced basal, hCG-stimulated and 25-hydroxycholesterol-supported testosterone production (by 80-90%) and the activities of cholesterol side-chain cleavage (about 80%) and 17 alpha-hydroxylase (about 65%). Infusion of exogenous LH in any of the regimens tested prevented these changes or increased the activities to values greater than those in normal serum-treated controls. Differences in immunodetectable contents of the two enzymes generally paralleled those in enzyme activities. There was a consistent trend in the effects of LH replacement regimens on these parameters of steroidogenic activity: continuous infusions were more effective than pulses at 2 h intervals and these in turn were more effective than pulses at 4 h intervals, suggesting that the frequency of LH exposure is more important than the amplitude of individual exposures in maintaining Leydig cell steroidogenic function.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1404083 TI - Stimulation of the release of [32P]guanosine 5'-diphosphate from G proteins in the rat anterior pituitary lobe by gonadotrophin-releasing and thyrotrophin releasing hormones. AB - Plasma membranes (1-2 mg protein) purified from the anterior pituitary lobes of adult male rats were incubated with 0.6 mumol [alpha-32P]guanosine 5' triphosphate (GTP) l-1 in an ATP-regenerating buffer at 37 degrees C for 60 min; during this incubation the [32P]GTP was hydrolysed and the nucleotide that was predominantly bound to the membranes was [32P]GDP. The release of [32P]GDP from the membranes was monitored at 37 degrees C; the amount released was proportional to the protein concentration and increased as a function of time. 5' Guanylylimidodiphosphate (Gpp(NH)p) increased [32P]GDP release by up to 30% at 0.1 mumol l-1. Although 10 nmol Gpp(NH)p l-1 had no effect on GDP release, it appeared to stabilize the hormonal effect by blocking further GDP-GTP exchange. Gonadotrophin-releasing hormone (GnRH) agonist and thyrotrophin-releasing hormone (TRH), at 0.1 mumol l-1 caused a maximum increase in the release of [32P]GDP of 31-38%. The GnRH agonist (0.1 mumol l-1) stimulated GDP release by 21%, 24%, 17% and 14% at 30 s, 1, 2 and 5 min, respectively. TRH (0.1 mumol l-1) stimulated GDP release by 38%, 30%, 17% and 16% at 30 s, 1, 2 and 5 min, respectively. A GnRH antagonist also stimulated [32P]GDP release, albeit less effectively than GnRH agonist; the antagonist did not inhibit agonist stimulation of GDP release. These results indicate that ligand binding to the GnRH and TRH receptors results in interaction of the receptor with a guanine-nucleotide-dependent transducer protein (G protein) and activation of GTP-GDP exchange.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404084 TI - Isolation of serine protease from granulated metrial gland cells of mice and rats with lectin from Dolichos biflorus. AB - Granulated metrial gland cells were the only cells in the endometria of pregnant mice and rats that reacted histochemically with fluoresceinated lectin (DBA) from Dolichos biflorus. Cell extracts of uteri of pregnant animals, separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and analysed by lectin overlay blotting, contained DBA-reactive, 40-50 kDa, doublet glycoprotein bands. This glycoprotein was purified on a DBA agarose affinity column. It was identified by amino acid sequencing as a serine protease closely related to granzymes of T lymphocytes. We conclude that this granzyme accounts for the selective reactivity of granulated metrial gland cells with fluoresceinated DBA in histological sections of uteri of pregnant rodents and show that DBA affinity columns can be used for purification of granzyme derived from granulated metrial gland cells. PMID- 1404085 TI - Maintenance of motility of fowl spermatozoa in vitro is prolonged by a low molecular weight factor derived from cultured chick embryo cells. AB - Gel filtration of a conditioned medium composed of the supernatant fluid removed from a 5-day culture of skeletal muscle cells from 9-day-old chick embryos with Bio-Gel P-2 revealed one peak of motility-prolonging activity (about 0.3 kDa), which was not present in fresh medium. Spermatozoa incubated in this fraction of the conditioned medium maintained their motility for at least 36 h at 37 degrees C. Both the formation of lipid peroxide and the leakage of lactic dehydrogenase of spermatozoa incubated in the conditioned medium fraction were lower than those incubated in the corresponding fresh medium. Initial rate of oxygen consumption of the spermatozoa incubated in the conditioned medium fraction increased compared with that of the fresh medium fraction. These results suggest that a low molecular weight factor(s) supplied by cultured cells effectively prolongs the motility of fowl spermatozoa, and that the effect could result from inhibition of the structural damage to the sperm membrane. PMID- 1404086 TI - Influence of photoperiod on the seasonal pattern of secretion of luteinizing hormone and testosterone and on the antler cycle in roe deer (Capreolus capreolus). AB - Annual variations in concentrations of luteinizing hormone (LH) and testosterone in plasma were analysed in relation to the antler cycle in six adult male roe deer exposed to a natural photoperiod (latitude 46 degrees 10'N) and in four adult males maintained in a constant short-day photoperiod (8 h light: 16 h dark) for a year, from the winter solstice at which time both groups of animals had antlers in velvet. The animals were sampled, every 15 min for 2 or 4 h at intervals of one month for a year. Under both natural and experimental conditions, LH concentrations were high from January to March, but in the experimental conditions they decreased between April and May-June, whereas in the natural conditions they increased. Plasma LH concentration was lowest between July and November in animals under natural photoperiod, whereas under 8 h light:16 h dark photoperiod a second increase in plasma LH occurred between August and September. Between March and August, concentrations of plasma testosterone increased under natural photoperiod, whereas under experimental photoperiod there was a biphasic pattern of plasma testosterone with peaks between February and May and between September and November. Under natural photoperiod, antlers were cast in November, 369 +/- 6 days after the previous antlers were cast. Under experimental photoperiod, antlers were cast after 193 +/ 10 days, and a new set developed. The sexual cycle of the male appears to be initiated by an endogenous rhythm in winter and is then maintained by hormonal changes resulting from increasing photoperiod in spring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404087 TI - The role of photoperiod on the initiation of the breeding season of the brushtail possum (Trichosurus vulpecula). AB - The role of photoperiod on the initiation of the breeding season of brushtail possums was investigated in possums housed in three light regimens: a short-day, a natural and a long-day photoperiod. Seven possums were housed in a natural photoperiod. Four possums were transferred to a short-day photoperiod (10 h light, 14 h dark) and eight possums to a long-day photoperiod (14 h light, 10 h dark) on 22 November, when the daylength was 13.34 h. The first rises in plasma progesterone concentrations were observed on 9 January +/- 9 days (n = 4), 11 March +/- 6 days (n = 7) and 6 May +/- 6 days (n = 8), for possums held in short day, natural or long-day photoperiods respectively. Similarly, births were observed on 12 January and 14 February in the short-day group, from 3 March to 8 May for the natural photoperiod group, and from 5 May to 8 August for the long day group. These results suggest that photoperiod is important in the timing of the breeding season. However, annual breeding will commence in a nonstimulatory long-day photoperiod. Thus a long-day photoperiod does not prevent breeding activity. PMID- 1404088 TI - Effect of duration of melatonin treatment on the onset and duration of oestrous cyclicity in ewes. AB - Forty-two Scottish Blackface ewes that lambed outdoors in March were removed from their lambs at the end of April and housed under natural daylength at 57 degrees N. Treatments (n = 7 ewes per treatment) commenced on 1 May and comprised daily oral dosing at 15:00 h with 3 mg melatonin dissolved in water and ethanol (4:1, v/v) for 30, 60, 90, 120 or 150 days. Control ewes received the vehicle alone. Ovarian activity was assessed by laparoscopy at monthly intervals with an additional interim observation in mid-July. Blood was sampled three times a week by jugular venepuncture and assayed for progesterone, prolactin and follicle stimulating hormone (FSH). Luteinizing hormone (LH) was determined in blood samples collected at 15 min intervals for 10 h on days 28, 60, 91, 119 and 150. Thirty days of melatonin treatment delayed (P < 0.01) first ovulation by about 1 month (mean interval +/- SEM from 1 May to progesterone > 1 ng ml-1, 165 +/- 4.5 days versus 132 +/- 9.2 days for controls). None of the ewes that received melatonin for 60 days ovulated before the end of melatonin treatment, but subsequently six of them did; the mean interval from 1 May to increased progesterone concentration was 75 +/- 1.2 days. All ewes receiving melatonin for 90, 120 and 150 days ovulated with corresponding mean intervals of 83 +/- 2.7, 85 +/- 1.3 and 87 +/- 2.2 days, respectively (P < 0.001 compared with controls).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404089 TI - Evidence that cortical granule formation is a periovulatory event in marsupials. AB - Formation of cortical granules was examined in superovulated oocytes from three marsupial species, brushtail possums (Trichosurus vulpecula) tammar wallabies (Macropus eugeniii) and grey short-tailed opossums (Monodelphis domestica) and in oocytes obtained during natural cycles in Macropus eugenii. Superovulation was induced by pregnant mares' serum gonadotrophin/gonadotrophin-releasing hormone (PMSG/GnRH) protocols and natural ovulation by removal of pouch young. Oocytes were collected after ovariectomy or by laparoscopically guided follicle aspiration into Hanks balanced salt solution (HBSS) supplemented with either 2.5% fetal calf serum (FCS) or 2.5% bovine serum albumin (BSA). Ovulated oocytes were collected by removing and flushing the oviducts with HBSS and fixed immediately for electron microscopy. There were no differences in the morphology or timing of formation of cortical granules between superovulated and naturally cycling animals. Cortical granules were absent from germinal vesicle (GV) stage follicular oocytes before the luteinizing hormone (LH) surge in all species. Dark cortical granules, similar in appearance to those seen in the oocytes of eutherian mammals, were found just beneath the plasma membrane (9 per 100 microns of plasma membrane) of preovulatory oocytes at germinal vesicle, metaphase 1 or anaphase 1 stages. In addition, they contained a number of less electron-dense cortical granules (12 per 100 microns plasma membrane). The cortical cytoplasm of preovulatory oocytes was rich in Golgi complexes actively involved in vesicle formation. Large numbers of dark cortical granules (90 per 100 microns plasma membrane) were found only in ovulated oocytes. A small number of cortical granules of lighter electron density were also present in ovulated oocytes. This suggests that the marsupial oocyte is following a very different timetable for cortical granule formation and accumulation from eutherian mammals and that oocytes of marsupials may not achieve cytoplasmic maturity until after ovulation. The significance of these events for fertilization and development remains to be established. PMID- 1404090 TI - Influence of gonadal hormones on odours emitted by male meadow voles (Microtus pennsylvanicus). AB - Free-living male meadow voles (Microtus pennsylvanicus) emit odours that are attractive to females at the beginning, but not at the end, of the breeding season. The effect of gonadal hormones on female-attractant cues was examined in males born and reared in long (14 h light day-1) and short (10 h light day-1) photoperiods that simulate daylengths in the breeding and nonbreeding seasons, respectively. Gonadectomy affected the attractant properties of odours emitted by long photoperiod, but not short photoperiod, males. Long photoperiod females preferred odours of intact rather than those of gonadectomized long photoperiod males, and odours of gonadectomized long photoperiod males rather than those of intact short photoperiod males. Females did not show a preference between the odours of intact and castrated short photoperiod males. Gonadal hormone replacement in males affected female responses to the odours emitted by long photoperiod, but not short photoperiod, gonadectomized males. Long photoperiod females did not display a preference between odours of intact long photoperiod males and gonadectomized long photoperiod males treated with testosterone or oestradiol. We conclude that in spring and summer gonadal hormones increase attractiveness of male odours; this effect may require aromatization of testosterone to oestradiol. Substrates that control attractiveness of odour cues in male voles appear to be unresponsive to androgens during the nonbreeding season. PMID- 1404091 TI - Osmotic shock of fertilized mouse ova. AB - The effect of osmotic changes on fertilized mouse ova was studied by measuring their survival, defined as development into hatching blastocysts, after exposure to various concentrations of ethanediol (ethylene glycol). In addition, a Boyle van't Hoff plot was derived from exposing ova to hypotonic and hypertonic solutions ranging from 0.1 to 2.8 osmol. Volume of ova was inversely proportional to osmolality over this range. Extrapolation of this relationship yielded a nonosmotic volume of the ova of 22.5%. Eighty-five per cent or more of the ova survived exposure to this wide range of concentrations and developed into blastocysts. The rate of development of ova exposed to anisotonic solutions was the same as that of controls. Ova underwent osmotic shock when abruptly diluted out of concentrated solutions of ethanediol with an isotonic solution. Their survival was highly dependent on the ethanediol concentration with which they had equilibrated before dilution, and the manner, rate and temperature of dilution. The longer the exposure to ethanediol the greater was the sensitivity of the ova to osmotic shock, reflecting permeation of ethanediol into the ova. Osmotic shock could be alleviated by dilution at a high temperature, and prevented by the use of sucrose as an osmotic buffer at 37 degrees C. Identification of the variables that influence osmotic shock of ova will be helpful in the systematic study of their cryopreservation. PMID- 1404092 TI - The contribution of the toxicity of a glycerol-egg yolk-citrate cryopreservative to the decline in human sperm motility during cryopreservation. AB - The contribution of the toxicity of glycerol-egg yolk-citrate (GEYC) cryopreservative medium to the loss of function of human spermatozoa during cryopreservation was determined by investigating the effect of mixing semen with the medium on sperm motility. The percentage of progressively motile spermatozoa, velocity (micron s-1) and lateral head displacement (micron) (mean +/- SEM, n = 28) were 55 +/- 4.1, 47 +/- 2.7, 4.4 +/- 0.2 and 32 +/- 3.8, 40 +/- 2.5, 3.6 +/- 0.25 and 15 +/- 2.5, 28 +/- 1.1, 2.8 +/- 0.15 in suspensions of washed spermatozoa prepared from fresh, GEYC-treated and frozen-thawed semen, respectively. The variables changed only slightly after incubation for 3 h. The toxicity of GEYC did not vary significantly between samples which survived the complete freeze-thaw cycle well or very poorly. The toxicity of GEYC is responsible for about 50% of the loss of progressively motile spermatozoa during the complete cryopreservation process, but has little effect on the quality of motility. Susceptibility to GEYC does not explain observed differences in the ability of semen samples to survive freezing. PMID- 1404093 TI - Changes in concentration of serum prolactin during social and reproductive development of the spotted hyaena (Crocuta crocuta). AB - A homologous radioimmunoassay system developed for humans was used to measure prolactin concentrations in spotted hyaenas. Concentrations of prolactin showed a significant (P < 0.05) decrease in lactating females, which is consistent with the infrequent suckling pattern of this species. This lack of hyperprolactinaemic conditions during lactation may explain the ability of females to resume reproductive activity soon after the loss of a litter, or even during lactation. Prolactin concentrations did not increase significantly during dispersion in male spotted hyaenas. This conforms to the pattern observed for cortisol, but differs from that for androgen, which fluctuates significantly with social suppression. Although comparative data from other species provide some circumstantial evidence for hyperprolactinaemic conditions during male dispersal, no obvious deductions regarding the recorded inverse relationship between prolactin and cortisol concentrations in mature males could be made. PMID- 1404094 TI - The effect of decrease in body temperature with Nembutal on meiosis and ovulation after induction by gonadotrophin-releasing hormone and luteinizing hormone in adult rats. AB - Sodium pentobarbital (Nembutal) is often used to block the pro-oestrous luteinizing hormone (LH) surge in rats. Nembutal is also known to lower body temperature. This study was designed to investigate whether Nembutal affected the time course of meiosis and timing of ovulation induced by exogenous hormones, and whether the possible effects of Nembutal on these processes were related to temperature. Gonadotrophin-releasing hormone (GnRH), the GnRH-analogue Ovalyse, or rat luteinizing hormone (LH) were administered to trigger resumption of meiosis and ovulation; Nembutal (35 mg kg-1 body weight) or saline was given 10 or 60 min later. Plasma profiles of LH were measured and Graafian follicles were studied histologically for meiotic progress and ovulation. Nembutal suppressed the spontaneous surge of LH at pro-oestrus and caused a long-lasting decrease in body temperature. If 1000 ng GnRH was given 2 h before the pro-oestrous LH surge, most of the oocytes had extruded a polar body 10 h later and most follicles had ovulated 14 h later. Nembutal given 1 h after GnRH delayed extrusion of the polar body and ovulation by about 2 h. Nembutal caused a similar delay in ovulation when it was administered after 100 ng of Ovalyse, and it also delayed meiosis when given after 1000 ng of LH. This effect of Nembutal was prevented if body temperature was maintained at 37 degrees C. The delaying effect of Nembutal on meiosis and ovulation induced by exogenous GnRH or LH is related to a long lasting decrease in body temperature. PMID- 1404095 TI - Spacing of fetuses and local competition in strains of mice with large, medium and small litters. AB - The tendency for fetuses to be evenly spaced along the uterine horn and the relationship of this to local competition between fetuses was examined in three strains of mice which characteristically produce large, medium and small litters. Local competition was assessed by correlating, within each uterine horn, the weight of each fetus or placenta with the mean distance to its immediate neighbours. Weights and distances were measured on day 19 of gestation, on the day before expected parturition and distances only on day 7. Average litter sizes (live fetuses) were 16.3 +/- 0.9, 11.7 +/- 0.6 and 7.2 +/- 0.5 (mean +/- SEM) in the large, medium and small litter strains, respectively (n = 7, 7 and 10, respectively). On day 19, the mean distance between fetuses was significantly less (P < 0.05) in the large strain (10.1 +/- 1.0 mm) than in the medium (14.0 +/ 1.2 mm) or small (13.5 +/- 1.0 mm) strains. Evenness of spacing, expressed as the standard deviation of distances between fetuses divided by the mean distance, improved from day 7 to day 19 of gestation in all three strains and effectively prevented local competition between fetuses in the medium litter (r = 0.04) and small litter strains (r = 0.17), but not in the large litter strain (r = 0.45, P < 0.01). Thus, local crowding does not seem to be detrimental to fetal growth in mice, except in strains specifically bred for large litters. PMID- 1404096 TI - Glycosphingolipids of rabbit endometrium and their changes during pregnancy. AB - The glycolipids of nonpregnant and pregnant rabbit endometrium were characterized using a combination of biochemical and immunochemical techniques. Quantitative analyses indicated a 70% decline in acidic glycolipid (ganglioside) content during early pregnancy (day 6), and a 2.5-fold increase in neutral glycolipid content during later pregnancy (day 26). The major gangliosides of rabbit endometrium were identified by thin-layer chromatography as GM3 and GD3, with minor amounts of GM1, GD1a and GT1b. The major neutral glycolipids were identified similarly as globo-series structures Gb3 and Gb4. Monoclonal antibodies (mAbs) directed to glycolipid antigens permitted the detection of additional glycolipid species, including sialylated, sulfated and fucosylated lacto-series structures. Difucosyl Ley structure (defined by mAb AH-6) and sulfated-galactosyl structure (defined by mAb VESP 6.2) were identified by indirect immunofluorescence along the luminal surface of the endometrium during the implantation period. Rapid changes in the glycolipid composition of endometrial cells during early pregnancy may facilitate embryo adhesion and trophectoderm outgrowth during implantation. PMID- 1404097 TI - Spontaneous degeneration of germ cells in normal rat testis: assessment of cell types and frequency during the spermatogenic cycle. AB - The occurrence of degenerating germ cells in the cycle of the seminiferous epithelium was measured in testicular tissues from eight normal adult rats. Testes were perfusion fixed, embedded in epoxy resin and, after sectioning a total of 180 randomly selected blocks at 1 microns, stained sections were examined by light microscopy; all cross-sectioned seminiferous tubules were categorized into one of 14 stages of the spermatogenic cycle. The number of degenerating cells per tubule was recorded in 2103 tubules. Degenerating germ cells were not detected at stages II-VI, and only rarely at stage VII (n = 366 tubules) in which one primary spermatocyte and one step 19 spermatid degenerated. All other stages exhibited a greater incidence of degenerative germ cells, particularly at stage XIV where, on average, the frequency of degenerating cells per round seminiferous tubule was about 40 times greater than at stage VII. The results indicated that, in the normal adult rat testis, the germ cells are least at risk of degeneration as they pass through stage VII. PMID- 1404098 TI - Effect of prostaglandins on luteal function during early pregnancy in pigs. AB - Luteal cells were obtained by digestion of luteal tissue of cyclic (day 12) and early pregnant (days 12, 20 and 30) pigs. Suspensions of the dispersed luteal cells (5 x 10(4) cells ml-1) were incubated for 2 h in minimum essential medium (MEM) alone (control) and MEM with different concentrations of prostaglandin F2 alpha (PGF2 alpha) and PGE2 (0.01, 0.1, 1, 10, 100 and 1000 ng ml-1) and luteinizing hormone (LH) 100 and 1000 ng ml-1, or with combinations of LH + PGF2 alpha and LH + PGE2. Net progesterone production was measured in the incubation media by direct radioimmunoassay. The overall response pattern of the luteal cells to exogenous hormones on day 12 of the oestrous cycle and pregnancy differed (P < 0.05) from treatment on day 20 and 30 of pregnancy. In general progesterone production was higher (P < 0.05) and the response to PGF2 alpha and PGE2 treatment was most obvious on day 12 of the oestrous cycle and pregnancy. Overall, PGF2 alpha stimulated progesterone production in a dose-dependent manner (P < 0.05). The response to PGE2 was of a quadratic nature (P < 0.05) in which the lowest and the highest doses of PGE2 were associated with a greater production of progesterone than were the intermediate doses. Treatment of luteal cells with PGF2 alpha + LH or PGE2 + LH caused overall inhibition (P < 0.05) of progesterone production compared with treatment with each hormone alone. This interaction was not affected by the dose of LH used. These findings indicate that PGF2 alpha and PGE2 are involved in the autocrine control of corpus luteum function. PMID- 1404099 TI - Origin of oestrus-associated glycoproteins in bovine oviductal fluid. AB - The aim of the present study was to determine whether the synthesis of an oestrus associated protein found in bovine oviductal fluid varies with oviductal region, stage of cycle or day of pregnancy. Explant culture was performed using oviducts recovered from naturally cycling animals either at oestrus or 12-14 days after oestrus. Three oviductal regions, the preampulla, ampulla and isthmus, were cultured individually in the presence of 20 muCi [35S]methionine in serum-free medium for 6 h at 37 degrees C. Synthesis of oestrus-associated protein was assessed by one-dimensional SDS-PAGE, fluorography and densitometry of radiolabelled bands. Significantly more oestrus-associated protein was synthesized by the ampullar region of the oviduct, although it was detected in explant culture media from both the isthmic and preampullar regions. A polyclonal antibody produced against oestrus-associated protein was used to localize the protein in paraffin-embedded sections of oviductal explant cultures and other bovine tissues. Localization of the protein in oviductal tissue sections varied with stage of cycle (oestrus > luteal > pregnant) and region of oviduct (ampulla > preampulla/isthmus). These findings indicate an effect of oviductal region and hormonal state (cycling versus pregnant) on the synthesis and secretion of the oestrus-associated protein. Lectin affinity studies indicated that galactosyl(beta 1,3)N-acetylgalactosamine and N-acetylglucosamine residues are associated with the oestrus-associated protein. PMID- 1404100 TI - Factors from fluid of the ovarian pocket that stimulate sperm motility in domestic hens. AB - Fluid was collected from the region of the peritoneum surrounding the ovarian pocket of domestic hens at about the time of ovulation. This fluid, diluted to 10%, increased the motility of chicken spermatozoa by a maximum of sixfold at 40 degrees C in vitro. Gel filtration revealed two peaks of motility-stimulating activity: one was identified as calcium and the other as a heat-labile substance of low M(r) (200). It is suggested that this motility-stimulating activity may facilitate fertilization, as spermatozoa are normally stored in a quiescent state within the oviduct and can be passively transported by cilia to the site of fertilization in the ovarian pocket. PMID- 1404101 TI - Expression of mRNA for follicle-stimulating hormone suppressing protein in ovarian tissues of cows. AB - The expression of bovine follicle-stimulating hormone (FSH)-suppressing protein (FSP) mRNA was investigated in different ovarian tissues of cows. Northern blot analysis, using a cDNA probe to bovine FSP, demonstrated that the FSP gene in the bovine ovary is highly expressed in a pool of isolated granulosa cells. Two bands (2.8 and 1.8 kb) were observed in all tissues expressing the mRNA. FSP mRNA was low in small antral follicles and increased in growing follicles to reach a maximum in preovulatory follicles. Low amounts of mRNA of steady state FSP were observed in all stages of the corpus luteum as well as in the corpus luteum of pregnant cows, in the corpus albicans and theca tissue, whereas this mRNA could not be detected in the liver. These results are consistent with the hypothesis that, in cows, FSP functions as an autocrine regulator in developing follicles to facilitate luteinization of granulosa cells. PMID- 1404102 TI - Plasma melatonin profiles of Romney Marsh sheep in natural photoperiod and in acutely extended darkness. AB - Plasma melatonin was measured at the summer and winter solstices and the autumn and spring equinoxes in Romney Marsh sheep held under natural conditions in South Australia (35 degrees S). The amount of melatonin detected was generally related to the extent of natural darkness, though the melatonin onset was particularly delayed after dusk in winter compared with other seasons. The duration of detectable melatonin was shorter in summer than at any other season. After each initial 24 h sampling, the sheep were resampled for a further 24 h in acutely extended darkness to mark the phase and duration of suprachiasmatic nuclei activity which is believed to be the source of the melatonin signal. The onset of high plasma melatonin was earlier than the time of natural sunset in spring and summer, but not different from the time of natural sunset in autumn and winter. The offset of high plasma melatonin was later than the time of natural sunrise at all times of year and particularly so in summer. Under the extended dark conditions, the duration of detectable melatonin was longer than that under natural photoperiod at all seasons of the year and the duration of melatonin was again shorter in summer than winter. If melatonin measurements under the conditions of extended darkness do reflect the phase and duration of suprachiasmatic nuclei function then the natural light of the photoperiod can, particularly during long photoperiod conditions, mask the expression of the pacemaker. The findings may have implications for the timing of the breeding season in Romney Marsh sheep. PMID- 1404103 TI - Observations on the turkey oviductal sperm-storage tubule using differential interference contrast microscopy. AB - Squash preparations of unfixed, uterovaginal junction mucosae revealed that openings to sperm-storage tubules were round or slit-like and were surrounded by either cilia, which were part of the uterovaginal junction surface epithelium, or nonciliated cells resembling the sperm-storage tubule epithelium. By focusing on different levels of the sperm-storage tubule (optical sectioning), connective tissue fibres and cells between individual sperm-storage tubules, epithelium and lumen of sperm-storage tubules containing resident spermatozoa were observed. An optical section through the sperm-storage tubule epithelium revealed basal nuclei and associated nucleoli, and refractile supranuclear lipid droplets. Luminal spermatozoa were distributed primarily in the distal third of the sperm-storage tubule and nearly always formed a tight bundle at its base. These spermatozoa were often observed slowly and synchronously oscillating. In two-thirds of the 30 week-old, non-photostimulated hens, sperm-storage tubules were fully formed. In contrast, the remaining hens possessed bud-like surface invaginations lacking discernible lumina. It was concluded that differential interference contrast microscopy offers better spatial and optical resolution of the sperm-storage tubule than other modes of light microscopy. PMID- 1404104 TI - Effect of pregnant mares' serum gonadotrophin on the micromorphology of antral follicles in heifers, with special reference to atypical granulosa cells. AB - Five Dutch-Friesian heifers were injected i.m. with 3000 iu pregnant mares' serum gonadotrophin (PMSG) on day 10 of the oestrous cycle, to study the effects on the number and micromorphological quality of antral follicles (> or = 0.3 mm in diameter). The ovaries were collected 48 h after PMSG injection. As well as the presence of mitotic figures and the absence of pyknotic nuclei in the granulosa, atypical granulosa cells were found in nonatretic follicles. These cells had an oblong nucleus and stained with toluidine blue. They were characterized by their dark cell matrix, and the presence of numerous free ribosomes and intermediate filaments of varying quantity. Atypical granulosa cells were micromorphologically similar to fibroblast-like cells in the theca. Their presence coincided with the occurrence of degenerative changes in the cytoplasm of nearby granulosa cells and they were more frequent in atretic follicles. The presence of atypical granulosa cells in follicles hitherto called nonatretic is therefore probably associated with the onset of follicular atresia. In the PMSG-treated heifers, the mean number of large (> or = 6.0 mm in diameter) antral follicles was greater than in the control group (18.4 +/- 4.0 versus 3.0 +/- 1.0), because of an increase in the number of large nonatretic follicles (11.8 +/- 4.4 versus 0.4 +/- 0.2). After hormone treatment, the mean number of medium-sized (3.0-5.9 mm) nonatretic follicles also increased (6.4 +/- 1.3 versus 1.8 +/- 1.0). PMSG did not change the mean number of nonatretic follicles < 3.0 mm or that of atretic follicles in the different size categories. However, when follicles hitherto called nonatretic, with atypical granulosa cells, were taken together with the group of atretic follicles, PMSG appeared to increase the mean number of large atretic follicles (13.6 +/- 2.4 versus 3.0 +/- 1.0). The mean number of medium-sized and large nonatretic follicles without atypical granulosa cells was markedly increased (3.8 +/- 1.0 versus 0.2 +/- 0.2 and 4.6 +/- 1.9 versus 0.0, respectively). The data demonstrate that PMSG stimulates the formation not only of nonatretic follicles > or = 3.0 mm, but also of atretic follicles > or = 6.0 mm. PMID- 1404105 TI - Superoxide dismutase activity, lipid peroxide production and corpus luteum steroidogenesis during natural luteolysis and regression induced by oestradiol deprivation of the ovary in pseudopregnant rabbits. AB - The relationship of oxygen free radicals to corpus luteum function in rabbits was explored during various stages of pseudopregnancy, including natural and induced luteal regression. Induced luteolysis was achieved during mid-pseudopregnancy by removal of an oestradiol capsule placed at the onset of pseudopregnancy, which suppressed ovarian oestradiol production. Activity of manganese superoxide dismutase (Mn SOD) was significantly and positively correlated with ovarian progesterone production (P < 0.01) throughout pseudopregnancy and during natural regression. Oestradiol deprivation for 12, 24 or 72 h resulted in declines in Mn SOD activity and progesterone secretion, although Mn SOD rose and corpus luteum steroidogenesis was restored to normal when the capsule was replaced for 48 h before assessment, having been removed for 24 h. Lipid peroxide and progesterone concentrations were not correlated, although a significant rise in lipid peroxides in the luteal tissue was detected after deprivation of oestradiol for 72 h. Changes in progesterone production and Mn SOD activity were not associated with alterations in concentration of prostaglandin F metabolite. These data suggest that Mn SOD may be involved in regulating function of the corpus luteum during pseudopregnancy in rabbits and that oxygen free radicals may play a role in regression of corpus luteum in this species. PMID- 1404106 TI - Seasonal pattern of luteinizing hormone and testosterone pulsatile secretion in young adult red deer stags (Cervus elaphus) and its association with the antler cycle. AB - Blood from stages aged 15 months (n = 6) was sampled at monthly intervals every 30 min for 24 h for 12 months, at 45 degrees S in New Zealand. Three extra samplings each for 24 h were carried out at about the anticipated time of antler casting. All samples were analysed for luteinizing hormone (LH) and testosterone and the resulting data further analysed by the Pulsar pulse detection routine. The animals were kept indoors under natural daylength and were fed ad libitum. All animals were weighed, antler status and size recorded and testes diameter was measured on each sampling day. Mean LH and testosterone pulsatily and plasma concentration varied seasonally. LH pulse frequency was low during autumn (2.5 pulses in 24 h), winter (1.0-1.5 pulses in 24 h) and early spring (1 pulse in 24 h) and lowest in late spring (0.2 pulse in 24 h) before rising in summer (1.0-4.0 pulses in 24 h). LH pulse amplitude and mean plasma concentration were low (< 1 ng ml-1) from March to November (autumn-spring); both rose to a peak in January (summer) of 3.4 and 1.6 ng ml-1, respectively. Testosterone pulse frequency was generally similar to LH except that slightly more pulses of testosterone than of LH were detected from March to November and more pulses of LH from November to February (summer). Testosterone pulse amplitude fell from March to November (5.3 ng ml-1 to undetectable) although there was a conspicuous peak in July (midwinter) of almost 5 ng ml-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404107 TI - Effect of testosterone and bovine follicular fluid on concentrations of luteinizing hormone and follicle-stimulating hormone in plasma of castrated rams that are homozygous carriers or non-carriers of the Booroola fecundity gene. AB - Castrated adult FecBFecB and Fec+Fec+ Booroola rams were injected with charcoal treated bovine follicular fluid (bFF) (a source of inhibin-like activity) or given testosterone implants to examine whether the fecundity gene (FecB) influences sensitivity to negative feedback hormones in males. Mean concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) did not differ between genotypes before treatment. In Expt 1, injections of 5 ml bFF, but not of 1 ml (each given four times at intervals of 8 h), significantly (P < 0.05) depressed concentrations of LH and FSH, but there was no effect of genotype. After treatment, gonadotrophin concentrations returned to pretreatment values and for 2-2.5 days scaled (divided by pretreatment mean) LH values (235 +/ 49 for FecBFecB and 96 +/- 26% for Fec+Fec+ rams; P < 0.05) and scaled FSH values (106 +/- 5 for FecBFecB and 85 +/- 5% for Fec+Fec+ rams; P < 0.05) were significantly higher in FecBFecB than in Fec+Fec+ rams in the group that received 5 ml bFF. Irrespective of genotype, treatment with 5 ml bFF did not reduce mean FSH to concentrations observed in testis-intact rams. In Expt 2, Silastic envelopes were implanted subdermally to give physiological or supraphysiological circulating concentrations of testosterone. Both doses significantly reduced scaled LH values in a biphasic manner, such that there was an initial suppression followed by a short-lived increase. During the initial period of suppression in the lower dose group, mean scaled LH values were significantly higher in FecBFecB than in Fec+Fec+ rams (48.3 +/- 7.5 versus 23.1 +/- 5.5%; P < 0.05). Low doses of testosterone decreased LH pulse frequency in both genotypes but decreased (P < 0.05) pulse amplitude and mean concentrations in the Fec+Fec+ animals only. In nonimplanted control rams, mean LH concentrations (in samples taken every 10 min for 12 h) were significantly lower in FecBFecB than in Fec+Fec+ rams (0.6 +/- 0.2 versus 1.3 +/- 0.1 ng ml-1; P < 0.05). The mean FSH response to testosterone was not related to genotype. These data suggest that expression of the FecB gene results in an altered sensitivity of the pituitary gland to changes in negative feedback from testicular hormones and that, irrespective of genotype, neither testosterone nor inhibin-like activity alone can fully control FSH secretion in castrated rams. PMID- 1404108 TI - Influence of prenatal photoperiod on postnatal prolactin secretion in red deer (Cervus elaphus). AB - Plasma prolactin concentrations were higher (P < 0.001) in newborn red deer calves whose mothers had been maintained for the last 14 weeks of gestation in long days (18 h light) (group L, n = 9) than in those whose mothers had been kept over the same period in short days (6 h light) (group S, n = 5). After transfer of all hinds and suckled calves on the day of birth to constant intermediate daylength (12 h light), prolactin concentrations decreased exponentially (P < 0.001) in group L calves, but not in group S, during the first 21 days. Thereafter, prolactin fell to a nadir in group L calves and rose to peak values in group S calves at 8-12 weeks post partum (P = 0.003), before converging again by 14 weeks. The pattern of prolactin secretion over the first 14 weeks of life was therefore significantly affected by prenatal photoperiod. Plasma prolactin concentrations in the adult hinds were higher (P < 0.001) in group L than group S at 4-10 weeks before parturition; they were similarly high around parturition and fell thereafter to baseline values after 7 weeks. These results provide evidence that deer fetuses respond to photoperiodic information, thereby acquiring a photoperiodic history in utero that influences postnatal responses to photoperiod. PMID- 1404109 TI - Arthritogenicity of Eubacterium species in the adjuvant arthritis model. PMID- 1404110 TI - Parvovirus arthritis mistaken for Lyme arthritis. PMID- 1404111 TI - Hypermobility of the joints in pediatric patients with endstage renal disease. PMID- 1404112 TI - Repetitive exercise induced ventricular tachycardia in a patient with rheumatoid arthritis taking low dose methotrexate. PMID- 1404113 TI - Myelodysplastic syndrome in association with erythema elevatum diutinum. PMID- 1404114 TI - "The cool patella sign". PMID- 1404115 TI - Erythropoietin: a hormone finds a purpose. PMID- 1404116 TI - Prolactin--a hormone with immunoregulatory properties that leads to new therapeutic approaches in rheumatic diseases. PMID- 1404117 TI - Links between fibromyalgia and myofascial pain syndromes. PMID- 1404118 TI - The Parry Romberg syndrome of progressive facial hemiatrophy and linear scleroderma en coup de sabre. Mistaken diagnosis or overlapping conditions? PMID- 1404119 TI - Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. PMID- 1404120 TI - The relation of extraarticular tenderness to inflammatory joint disease and personality in patients with rheumatoid arthritis. AB - We measured the pain tenderness threshold at 16 fibrositic tender points in 44 consecutive patients with rheumatoid arthritis (RA) attending the outpatient rheumatology clinic of a university hospital. Pressure threshold measurements were transformed to z units to equalize the weights of the values at different anatomic sites and were then summed. This pain tenderness score correlated with the joint score index (p less than 0.02, r = -0.363), signifying a low pain threshold in the patients with a high joint score index. In contrast to this, the pain tenderness score was not explained by either personality factors or the generalized disease activity measuring variables (erythrocyte sedimentation rate, C-reactive protein). Our results show that the fibrositic point tenderness is real in RA, and that the tenderness is augmented near the active joints. The pain tenderness score of patients with RA is not affected by the subject's personality but may relate to sensitization of the pain fibers in arthritic joints. PMID- 1404121 TI - Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity. AB - Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03). PMID- 1404122 TI - Accelerated nodulosis during low dose methotrexate therapy for rheumatoid arthritis. An analysis of ten cases. AB - OBJECTIVE: To obtain information on the occurrence of accelerated nodulosis during methotrexate (MTX) for rheumatoid arthritis (RA), localization, size and presence in heart and lungs of these nodules, predisposing factors, relationship with other extraarticular manifestations (EAM) and their histological features. METHODS: Ten patients with accelerated nodulosis were studied. Four participated in a double blind study of MTX and azathioprine. Patient characteristics, localization, size and histopathology of new nodules were determined. Echocardiography and chest roentgenograms were performed. RESULTS: Accelerated nodulosis occurred exclusively during treatment with MTX in our double blind study. The estimated incidence was 8%. One patient reported was rheumatoid factor negative. Newly developed nodules were small, and located in the fingers in all patients and in additional sites in 7. Pretreatment nodules were not found in the fingers. In one patient nodules on the mitral valve were found, but this was not likely to be associated with the use of MTX. No new pulmonary nodules were found. Other EAM developed concurrently in 4 patients. Histopathology revealed typical rheumatoid nodules. In 3 patients nodulosis regressed after MTX was stopped. In 2 of them they recurred after a rechallenge. CONCLUSIONS: Accelerated nodulosis during MTX for RA is not rare, and occurs despite good clinical response of polyarthritis. Rheumatoid factor positivity is not a prerequisite. New nodules are small and preferentially located in the fingers. Recurrence after rechallenge with MTX suggests causality. PMID- 1404123 TI - Psoriatic arthritis: clinical response and side effects to methotrexate therapy. AB - In the last decade, methotrexate (MTX) has emerged as a useful second line agent for a variety of arthritides. However, there still exists some reluctance for its wider use mainly because of concerns about its liver side effects. We describe our clinical experience with this drug in psoriatic arthritis (PsA). The study group included 24 men and 16 women, with a mean age of 47 years (16-75), with oligoarticular (13) or polyarticular (27) involvement, with a mean disease duration of 12 years (1-36). Patients received a mean dose of 11.2 mg of MTX orally/week during a mean period of 34 months (6-132). Seven had been previously treated with other second line agents. Thirty-eight patients had an excellent or good response. In them, the erythrocyte sedimentation rate dropped in a mean of 38 mm/h. Only 2 patients had a rather poor response. Two patients discontinued the medication because of side effects: leukopenia in one and stomatitis in the other. Eleven patients presented with liver test abnormalities: 3 mild, 6 moderate and 2 severe. Seven patients had 11 liver biopsies. Except for one, none had evidence of cirrhosis or inflammation. Indeed, no changes were observed in the histopathology in those with repeated biopsies. The case reported as cirrhosis occurred very early in the course of MTX therapy. He continued taking MTX treatment without further deterioration of liver chemistry and/or histology. It is concluded that MTX is an effective and safe agent in PsA. Results also indicate that it is not necessary to perform liver biopsies on a routine basis. PMID- 1404124 TI - Glucocorticoid receptor in patients with lupus nephritis: relationship between receptor levels in mononuclear leukocytes and effect of glucocorticoid therapy. AB - We investigated the clinical significance of glucocorticoid receptor determination in 20 patients with systemic lupus erythematosus (SLE) who afterwards developed nephrotic syndrome. Glucocorticoid receptor concentrations in mononuclear leukocytes (MNL) in these patients were comparable with those in both other patients with SLE and healthy persons. Improvement in urinary protein excretion and in disease activity, which was scored according to the SLE Disease Activity Index system of the University of Toronto, closely related to the glucocorticoid receptor concentrations in MNL isolated from the corresponding patients. In summary, glucocorticoid receptor determination in patients with lupus nephritis may be a predictive clue for assessing responsiveness to glucocorticoid therapy. PMID- 1404125 TI - IgG autoantibody to the collagen-like region of Clq in hypocomplementemic urticarial vasculitis syndrome, systemic lupus erythematosus, and 6 other musculoskeletal or rheumatic diseases. AB - We previously found that the Clq precipitin in sera from patients with hypocomplementemic urticarial vasculitis syndrome is an IgG autoantibody to Clq. We report here a prevalence study of this autoantibody in 162 patients with musculoskeletal or rheumatic diseases including hypocomplementemic urticarial vasculitis syndrome, systemic lupus erythematosus (SLE), and rheumatoid arthritis uncomplicated by vasculitis. The autoantibody, which binds only to the collagen like region of Clq, was found almost exclusively in hypocomplementemic urticarial vasculitis syndrome (100%) and SLE (35%) sera. Our results support the idea that among rheumatic diseases, anti-Clq autoantibody develops in disorders characterized by immune complex mediated injury, particularly of cutaneous and glomerular microvasculature. PMID- 1404126 TI - A radiographic comparison of erosive osteoarthritis and idiopathic nodal osteoarthritis. AB - Clinical, radiographic and histologic features suggest that inflammation is central to the pathogenesis of erosive osteoarthritis (OA). Since mediators of inflammation may activate osteoclasts and stimulate release of metalloproteinases in joint cartilage, we hypothesized that patients with erosive OA may have more joint space narrowing and less proliferative bone response (osteophytes, sclerosis) than those with idiopathic nodal OA. Hand radiographs of 33 patients with erosive OA and 33 age and sex matched patients with nodal OA were evaluated for prevalence and severity of joint space narrowing, osteophytes, subchondral sclerosis, subchondral cysts, erosions and subchondral collapse. While the prevalence and severity of OA was greater at each joint in erosive OA than in nodal OA, significant differences (p less than 0.05) were confined largely to the interphalangeal joints. Among patients with erosive OA, radiographic features of OA were more severe in joints with erosive changes than in joints that did not show erosive change (p less than 0.01 in most cases). Notably, when joints with erosive change were excluded, only joint space narrowing was more severe in patients with erosive OA than in the corresponding joints of patients with nodal OA (p less than 0.001). Our analysis did not support the hypothesis that inflammatory mediators modify chondro or osteoneogenesis in erosive OA. PMID- 1404127 TI - Effects of loading on the synthesis of proteoglycans in different layers of anatomically intact articular cartilage in vitro. AB - The anatomically intact articular cartilage (approximately equal to 2.5 cm2) of whole bovine sesamoid bones was cultured on its bone support. A load of 5 kg was applied intermittently at 0.3 Hz by a specially designed loading apparatus for 7 days. [35S]-sulfate was added during the last 17 h of the experiment. Loading induced a 40% increase in [35S]-sulfate incorporation into aggrecans and an almost 3-fold increase in the synthesis of small proteoglycans. The loading effects occurred mainly in the upper half of the articular cartilage. Samples left unloaded for 7 days and then loaded for 7 days likewise showed an increase in [35S]-sulfate incorporation compared with unloaded controls. PMID- 1404128 TI - Bronchoalveolar lavage and transbronchial biopsy in spondyloarthropathies. AB - Fourteen patients (12 men, 2 women) with spondyloarthropathies underwent bronchoalveolar lavage (BAL), transbronchial biopsy (TBB) and other respiratory investigations. BAL revealed lymphocytosis and increased nonaltered neutrophil polynuclears in a smoker and an isolated lymphocytosis in one patient with restrictive syndrome and radiographic apical fibrosis. TBB showed interstitial fibrosis in the 2 patients and in 3 others who are all nonsmokers and among whom 2 had a restrictive syndrome. Subclinical alveolitis in spondyloarthropathies is absent. Interstitial fibrosis is not rare and its frequent association in a restrictive syndrome suggests a mechanical origin. PMID- 1404129 TI - Followup in psoriatic arthritis: relationship to disease characteristics. AB - We investigated whether patient disease characteristics can explain differences in patients registered at the psoriatic arthritis clinic before 1987 who were seen regularly (139, "regular") to those who had not been seen for 2 years before 1989 (165, "inactive"). Despite a higher percentage of women in the regular group (p = 0.0058), logistic regression analysis identified no significant differences in disease severity or treatment at the first or last assessment before 1987. A followup study in 1989 revealed that of the 165 inactive patients, 20 had died and 64 had moved away. Of the 81 remaining patients, 18 were not interested, 18 were seeing other physicians, and 45 returned for followup. The latter 45 patients were compared to 85 of the regular patients who were seen during the same period. Both groups demonstrated similar disease attributes at first and last assessments before 1987. At their 1989 assessments, the same degree of disease progression was noted in both groups. Thus, loss to to followup appears to be random, and should not influence further studies of these patients. PMID- 1404130 TI - Effect of flurbiprofen on cytokine production by human monocytes and U-937 and THP-1 cell lines. AB - Possible effects of nonsteroidal antiinflammatory drugs (NSAID) on inflammatory mediators other than arachidonic acid metabolites which might contribute to the antiinflammatory effects of these drugs have not been fully explored. We investigated the effects of an NSAID, flurbiprofen, on production of the cytokines tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) by human peripheral blood monocytes and by the human cell lines U-937 and THP-1. Cytokine production was induced by 1 microgram/ml bacterial lipopolysaccharide (LPS) in both monocytes and cell lines, and cytokine levels in supernatants were measured by enzyme immunoassay. In monocytes, IL-6 was the major product while in both cell lines, TNF alpha was the major product. Flurbiprofen caused moderate inhibition of IL-1 beta and TNF alpha production by stimulated monocytes, but did not affect IL-6 production. In contrast, flurbiprofen completely abolished IL-6 production by both cell lines and substantially inhibited IL-1 beta and TNF alpha production. These observations raise the possibility that inhibition of cytokine production by flurbiprofen may contribute to the antiinflammatory properties of this drug. PMID- 1404131 TI - Tetracyclines suppress matrix metalloproteinase activity in adjuvant arthritis and in combination with flurbiprofen, ameliorate bone damage. AB - Tetracyclines are potent inhibitors of 2 major matrix metalloproteinases which have been implicated in connective tissue degradation: collagenase and Type IV collagenase/gelatinase. We directly identified these enzyme activities in extracts of inflamed paw tissue from rats with adjuvant arthritis. Oral tetracycline therapy suppressed metalloproteinase activity in arthritic tissue, but even very high doses failed to exhibit substantial antiinflammatory efficacy (reduced joint swelling and paw diameter). Flurbiprofen, a conventional nonsteroidal antiinflammatory drug, reduced inflammatory indices as expected. The combination of the 2 agents administered orally completely inhibited collagenase activity, significantly inhibited gelatinase activity and produced substantial normalization of radiographic joint damage, far greater than either drug alone. Tetracycline inhibition curves in vitro suggest that the collagenase in this tissue is not of fibroblast origin. Tetracycline derivatives might be useful adjuncts to prevention of tissue damage in chronic inflammatory arthritides. PMID- 1404132 TI - The fibromyalgia and myofascial pain syndromes: a preliminary study of tender points and trigger points in persons with fibromyalgia, myofascial pain syndrome and no disease. AB - Four experts on myofascial pain syndrome (MFP) performed trigger point examinations and 4 experts on fibromyalgia performed tender point examinations on 3 groups of subjects (7 patients with fibromyalgia, 8 with MFP, and 8 healthy persons) while blinded as to diagnosis. Local tenderness was common in both disease groups (65-82%), but was elicited in a greater proportion of MFP experts' examinations (82%). Active trigger points were found in about 18% of examinations of patients with fibromyalgia and MFP, but latent trigger points were rare in all groups. A more liberal definition of trigger point, however, resulted in a 38 and 23% positive rate among patients with fibromyalgia and MFP, respectively. Taut muscle bands and muscle twitches were common (50 and 30%, respectively) and noted equally in all 3 diagnostic groups. Problems with reliability were identified for taut bands, muscle twitch, and active trigger points. Our data are exploratory and tentative, but suggest that attention to definition and reliability are required to advance our knowledge of these common syndromes. PMID- 1404133 TI - The economic impacts of juvenile rheumatoid arthritis. AB - Our study documents the direct costs, family costs and community (extra school) costs. One hundred and twenty families with children who had juvenile rheumatoid arthritis (JRA) diagnosed by established criteria and who lived in New England were asked to participate. All data except inpatient charged were collected via questionnaire. The questionnaire return rate was 59% (N = 70). The mean annualized direct cost/child was 7,905 (inpatient, $1,717; outpatient, $5,700; and nonmedical, $488). Family costs averaged $1,524/year (out of pocket medical and nonmedical, $1,196; lost salary, $328), which represented 5% of mean family income. The mean extra school cost was $1,449/9 months. The economic impacts of JRA appear to be substantial. PMID- 1404134 TI - Intracranial findings in progressive facial hemiatrophy. AB - There have been infrequent reports of cerebral lesions associated with progressive facial hemiatrophy. Six children with progressive facial hemiatrophy were evaluated. Four were referred for evaluation of neurological deficits: 2 with seizures, one with left hemiparesis and one with learning problems. The remaining 2 patients had only facial hemiatrophy. Cranial computed tomography (CT) in 5 patients revealed the bony and soft tissue defects, but cerebral calcifications were seen in only 3 patients. Cranial magnetic resonance imaging (MRI) demonstrated areas of increased signal in the ipsilateral white matter on T2 weighted images in all 5 patients with upper facial atrophy. Ipsilateral cerebral lesions with progressive facial hemiatrophy may be more common than once believed. MRI sometimes reveals abnormalities of the white matter even in patients without neurologic symptoms, and may be more sensitive than CT in the diagnostic evaluation of patients with progressive facial hemiatrophy. PMID- 1404135 TI - Antibodies to lipid A in pauciarticular juvenile arthritis: clinical studies. AB - IgG antibodies to monophosphoryl lipid A (MPL) are more concentrated in synovial fluids than in the blood of children with pauciarticular juvenile arthritis. Correlations between IgG anti-MPL levels and numbers of inflamed joints were highly significant in 2 of 10 patients followed for 8 years and suggestive in 2 patients followed for shorter periods. A fifth patient had a correlation between IgM anti-MPL and joint count. PMID- 1404136 TI - Exocrine pancreatic function in children with systemic lupus erythematosus. AB - We examined the incidence and spectrum of pancreatic disease in pediatric systemic lupus erythematosus (SLE). We measured serum immunoreactive cationic trypsinogen (IRT) in 185 samples obtained from 35 patients with SLE. Fifteen patients (43%) had elevated IRT levels on at least one occasion. Serum samples were obtained in 20 of 35 patients before start of treatment. Seven of these 20 patients (35%) had elevated IRT levels at diagnosis, which slowly returned to normal as their disease was controlled with treatment. A further 3 of these 20 patients in whom we had sera at diagnosis had elevated levels at some course during their illness. Of the remaining 15 patients in whom sera was not available at diagnosis, 5 patients had increased IRT levels on at least one occasion. We show that elevated IRT levels are common in pediatric SLE, but there was no apparent association with drugs such as prednisone and azathioprine. However, high levels of IRT at the time of diagnosis may be related to an underlying disease component such as vasculitis. PMID- 1404137 TI - Childhood linear scleroderma: a possible role of thermography for evaluation. AB - Linear scleroderma is a rare, at times debilitating, disease with an unpredictable course. Currently, there is no satisfactory objective method for assessment of disease activity upon which to base therapeutic decisions. We evaluated 11 children with 18 linear scleroderma lesions (mean age 11.7 years, mean duration of disease 5.1 years) for disease severity and the presence of immunologic abnormalities, and attempted to correlate these results with thermography. Positive thermography was defined as warmer than surrounding skin or opposite limb by 0.5 degrees C. Six patients were thermography positive. Mean age, sex, disease duration and the presence of hypergammaglobulinemia and autoantibodies were similar in thermography positive and thermography negative patients. Six of 18 linear scleroderma lesions were thermography positive. All 3 new or expanding lesions were thermography positive. All 3 lesions that were resolving clinically were thermography negative. Three of 12 lesions that were clinically unchanged over a 6-month period were also thermography positive. In summary, thermography is a noninvasive test that appears to demonstrate active lesions in linear scleroderma. It is not influenced by previous soft tissue damage induced by linear scleroderma and may enable better monitoring of the effectiveness of proposed therapies. PMID- 1404138 TI - Upper airway obstruction as the sole manifestation of rheumatoid arthritis. AB - A 51-year-old woman with a history of rheumatoid arthritis (RA) suddenly developed laryngeal stridor. Rheumatoid factor was positive and the erythrocyte sedimentation rate was elevated, but she had no evidence of acute peripheral arthritis at this time. A flexible laryngoscopy revealed cricoarytenoid arthritis which was the sole clinical manifestation of active RA. Involvement of the cricoarytenoid joints must be considered in patients with RA with laryngeal stridor even in the absence of active peripheral arthritis. PMID- 1404139 TI - Drug induced systemic lupus erythematosus due to ophthalmic timolol. AB - We report a case of systemic lupus erythematosus (SLE) apparently induced by topical use of ophthalmic timolol maleate, a beta adrenergic blocking agent. The patient developed fever, malaise, pleurisy and recurrent sterile pleural effusions while taking no medication other than timolol. Antinuclear antibodies in a homogenous pattern, and markedly elevated histone antibodies (IgG anti-(H2A H2B)-DNA) were present while antibodies to native DNA were absent. After discontinuation of the timolol, his symptoms improved promptly and the pleural effusions resolved. To our knowledge, this is the first report of timolol induced SLE. PMID- 1404140 TI - Jaccoud's arthropathy of the shoulders in systemic lupus erythematosus. AB - A man with longstanding systemic lupus erythematosus who developed anterior dislocation of both shoulder joints is described. He also had typical Jaccoud's deformities of his hands and feet. PMID- 1404141 TI - Systemic lupus erythematosus and pheochromocytoma. AB - A 40-year-old Chinese woman with systemic lupus erythematosus (SLE) developed labile blood pressure 3 years after her onset of high blood pressure. Pheochromocytoma was subsequently found and removed. Postoperatively her hypertension improved without change in her SLE activity. Our case demonstrates pheochromocytoma can be a cause of hypertension in SLE. PMID- 1404142 TI - Prosthetic knee infection due to Achromobacter xylosoxidans. AB - Achromobacter xylosoxidans is an aerobic gram negative organism that has been infrequently implicated in clinical infections in a variety of anatomical sites. We describe a case of a prosthetic knee infection due to Achromobacter xylosoxidans in a patient with rheumatoid arthritis receiving high dose prednisone. PMID- 1404143 TI - Heterotopic ossification presenting as acute arthritis. AB - We describe a patient with acute myeloblastic leukemia in remission who developed painful, swollen knees 6 weeks after being ventilated for acute respiratory distress syndrome. Synovial fluid analysis was nondiagnostic and initial radiographs of his knees were normal. Repeat radiographs 5 weeks later showed periarticular calcification and the diagnosis of heterotopic ossification was made. Heterotopic ossification should be part of the differential diagnosis of acute arthritis in critically ill patients. PMID- 1404144 TI - Pneumocystis carinii pneumonia following cyclosporine A and methotrexate treated rheumatoid arthritis. PMID- 1404145 TI - Methotrexate may lower seizure threshold in patients with epilepsy. PMID- 1404146 TI - Jaccoud's arthropathy in a patient with necrotizing vasculitis. PMID- 1404147 TI - A reappraisal of the measurement of disease occurrence in rheumatoid arthritis. PMID- 1404148 TI - Functional and immunochemical heterogeneity of antiphospholipid antibodies: a classification. PMID- 1404149 TI - The microbial cause of rheumatoid arthritis: time to dump Koch's postulates. PMID- 1404150 TI - Hit and run, hit and hide or permanent hit: why it is premature to dump Koch's postulates in rheumatic diseases. PMID- 1404151 TI - Renal involvement in primary antiphospholipid syndrome. AB - Our objective was to define the renal involvement in primary antiphospholipid syndrome (APS). We studied 20 patients with primary APS. Fourteen were women, mean age 34.4 years. None met ARA criteria for systemic lupus erythematosus. All patients underwent complete renal function studies. The presence of hypertension was also investigated. Renal disease was found in 5 patients, and was characterized by proteinuria, hypertension and renal failure. Kidney biopsy was performed in these 5 patients, showing thromboses of the microvasculature, mesangiolysis, mesangial interposition, electron lucent subendothelial material and ischemic obsolescence of glomeruli. Arterioles showed luminal narrowing due to medial hypertrophy, mucoid thickening of the intima, thrombosis and fibrosis. We found renal disease in 25% of our patients with primary APS. Biopsy findings were consistent with a thrombotic microangiopathy involving both arterioles and glomerular capillaries. PMID- 1404152 TI - Upper airway disease in systemic lupus erythematosus: a report of 4 cases and a review of the literature. AB - We report the occurrence of life threatening upper airway complications in 4 of 158 patients with systemic lupus erythematosus (SLE) admitted to our hospital over a 6-year period and review published reports on this complication. The patients included in our study were identified through a computer search of our hospital medical records. Patients' charts were reviewed and the diagnosis confirmed by currently accepted criteria. The clinical features of SLE in all the published cases were assessed and compared to those found in our patients. We found that although upper airway involvement is uncommon in SLE, occurring with a relative frequency of 4/158 patient admissions, endotracheal intubation in patients with active SLE may result in the development of life threatening upper airway complications. We suggest that patients with active SLE who require intubation should be observed for the development of upper airway symptoms. PMID- 1404153 TI - Patients with systemic lupus erythematosus at risk for Pneumocystis carinii pneumonia. AB - We describe 6 cases of patients with systemic lupus erythematosus (SLE) who developed Pneumocystis carinii pneumonia. All were treated with high dose corticosteroids, and all developed the infection within 4 months of beginning new or revised cytotoxic therapy. All patients tested (5 of 6) were negative for human immunodeficiency virus (HIV). Those patients who developed Pneumocystis carinii pneumonia had more severe lymphocytopenia (median 595 vs 833/mm3) and received higher doses of corticosteroids (median prednisone dose = 43 vs 20 mg/day) than other patients with active SLE. A threshold lymphocyte count of 350/mm3 identified 4 of 6 cases but only 1 of 20 controls. Patients with SLE treated with high dose corticosteroids and cytotoxic drugs and with severe lymphocytopenia may be at increased risk for this opportunistic infection. PMID- 1404154 TI - Macrophage infiltration in the skin of patients with systemic sclerosis. AB - We stained skin specimens from 31 patients with systemic sclerosis with monoclonal antibodies to macrophages and T lymphocytes to characterize the cellular infiltrates. Not only T lymphocytes but macrophages were also identified, and macrophages were observed between collagen bundles as well as around skin adnexa and vessels. In addition, the ratio of macrophages to T lymphocytes was high, particularly in severely affected skin. There was no close relationship with disease duration. Our results suggest that cutaneous macrophages always play a role in scleroderma. PMID- 1404155 TI - Mechanisms of pathogenesis in scleroderma. I. Overproduction of interleukin 6 by fibroblasts cultured from affected skin sites of patients with scleroderma. AB - Fibroblasts were cultured from affected skin sites of patients with progressive systemic sclerosis (PSS), from unaffected skin sites of the same patients, and from a healthy donor. The concentration of interleukin 6 (IL-6) in culture medium conditioned by the growth of early passage cells was determined by radioimmunoassay and by quantitative bioassay. Results demonstrated that fibroblasts from affected PSS skin produce from 6 to 30-fold higher levels of biologically active IL-6 compared to unaffected and control cells. In contrast, serum IL-6 concentrations in 6 of 8 patients examined were not significantly different from healthy donors. Serum IL-6 levels were elevated 2 to 3-fold in 2 of 8 patients examined. Thus, the overproduction of IL-6 by affected scleroderma fibroblasts does not necessarily correlate with a systemic increase in IL-6, but may increase its concentration locally. In view of its biological activities, including stimulation of antibody production and T cell activation, the overproduction of IL-6 by PSS fibroblasts in the lesions may play a significant role in the pathogenesis of PSS and may profoundly influence the course of the disease. PMID- 1404156 TI - Mechanisms of pathogenesis in scleroderma. II. Effects of serum and conditioned culture medium on fibroblast function in scleroderma. AB - Scleroderma (progressive systemic sclerosis; PSS) is a connective tissue disorder in which excessive collagen is deposited in the skin and internal organs. Mediators of abnormal fibroblast function in PSS have not yet been identified. Our objective was to examine the possibility that factors present in serum from patients with PSS, or in culture medium conditioned by PSS fibroblast growth, serve to regulate fibroblast function. Fibroblasts from affected and unaffected skin sites of patients with PSS and from normal adult skin were cultured in the presence of various human sera or conditioned media. Results indicate that (1) the proliferative influence of serum of patients with PSS is not different from that of normal donors, (2) increased proliferation and procollagen gene expression are not linked in affected or unaffected dermal fibroblasts, and (3) affected PSS fibroblasts produce a stimulatory factor(s) for procollagen gene expression to which they are differentially sensitive. PMID- 1404157 TI - Management of suspected giant cell arteritis: a decision analysis. AB - We used decision analysis to compare 4 strategies for managing suspected giant cell arteritis (GCA): treat no patients, treat all patients, perform temporal artery biopsy and only treat positive cases, or biopsy and treat all cases irrespective of the result. The "treat no patients" strategy is preferred only if the likelihood of disease is less than 2%. The "biopsy and treat positive cases" strategy predominates for intermediate likelihood of disease (50%) and is insensitive to altering the probability of any key variables. The "biopsy but treat irrespective of the result" strategy becomes preferred at likelihood of disease of 81%. However, this result was sensitive to alteration of the key variables. Empirical therapy without biopsy would only be preferred if the likelihood of disease exceeded 90% and the disutility one attaches to treating under uncertainty is low at high probability of disease. Management of suspected GCA should be guided by the results of temporal artery biopsy in the majority of cases. At high likelihood of disease, temporal artery biopsy may be of value independent of its usefulness in determining management strategy. Further research should be directed towards improving the accuracy of diagnosis, defining the risk of iatrogenic complications and estimating utilities for the outcomes. PMID- 1404158 TI - Character of precolumbian North American spondyloarthropathy. AB - Shared characteristics and concurrent occurrence of rheumatoid arthritis (RA) and spondyloarthropathy in contemporary populations have compromised development of clear diagnostic criteria for distinguishing them. Although modern populations contain individuals with both RA and spondyloarthropathy, ancient populations often manifest only one. The presence of spondyloarthropathy as the sole erosive disease in selected ancient populations allows further clarification of its nature. The tendency towards pauciarticular, asymmetrical involvement, axial involvement and peripheral joint fusion in these populations clarifies diagnosis and distinguishes this phenomenon from RA. The significance of peripheral joint fusion appears to be unequivocally established on the basis of these findings. PMID- 1404159 TI - Pathogenetic role of Chlamydia, Yersinia and Borrelia in undifferentiated oligoarthritis. AB - We studied the cellular and humoral immune response to Chlamydia trachomatis, Yersinia enterocolitica and Borrelia burgdorferi in paired samples of peripheral blood and synovial fluid (SF) in undifferentiated oligoarthritis, reactive arthritis (ReA) and rheumatoid arthritis. Antigen specific lymphocyte proliferation was found in SF of 43% of patients with ReA and 34% of patients with undifferentiated oligoarthritis. C. trachomatis was the most frequent single agent. HLA-B27 was positive in 83% of patients with ReA and in 62% of patients with undifferentiated oligoarthritis with antigen specific lymphocyte proliferation. Antigen specific lymphocyte proliferation correlated poorly with the specific antibody response. Only chlamydial antigen was detected in SF cells using monoclonal antibodies. We conclude that some patients with undifferentiated oligoarthritis may have a forme fruste of ReA. This finding is important in view of recent evidence supporting the efficacy of antibiotic therapy in ReA. PMID- 1404160 TI - HLA-DP restricted Chlamydia trachomatis specific synovial fluid T cell clones in Chlamydia induced Reiter's disease. AB - Synovial fluid (SF) mononuclear cells from a patient with Chlamydia trachomatis induced acute Reiter's disease were directly by limiting dilution in a representative protocol using phytohemagglutinin in the cloning medium. Out of 76 alpha beta-TCR+ CD4+ T lymphocyte clones, 7 were shown to specifically recognize C. trachomatis in a proliferation assay. The antigen recognition of these clones was HLA-DP restricted. Unexpectedly, 2 HLA-DR restricted clones showed a proliferative response to Yersinia enterocolitica O3, though the patient had no history of yersinia infection. The high frequency of SF derived T cells with specificity for species-specific chlamydial antigens and the limited diversity of HLA class II restriction of these clones may indicate an oligoclonal synovial T cell response to persistent intraarticular chlamydia. PMID- 1404161 TI - Prevalence of cartilage shards in synovium and their association with synovitis in patients with early and endstage osteoarthritis. AB - It has been suggested that incorporation of shards of fibrillated cartilage into the synovium is a cause of synovitis in osteoarthritis (OA). We examined the prevalence with which fragments of cartilage are seen in synovium, and their association with synovitis, in patients with endstage OA and early OA of the knee. Samples of synovium were obtained from 12 patients with endstage OA who were undergoing knee joint replacement and 30 with only mild/moderate radiographic changes of OA who exhibited articular cartilage changes of OA at arthroscopy. The presence of cartilage shards was sought in synovium from the medial and lateral tibiofemoral compartments and the suprapatellar pouch of each patient. Comparable volumes of the synovial lining from patients with endstage and early OA were examined, and tissue mononuclear cell infiltration was graded as an indicator of synovitis. Cartilage shards were seen in synovium from 7 of 12 patients with endstage OA, all of whom had synovitis. No topographic relationship was found between shards and mononuclear cell infiltration. In contrast, cartilage fragments were not seen in synovium from any of the 30 patients with early OA, although 9 of them had full thickness cartilage ulcers and 17 had evidence of synovitis. PMID- 1404162 TI - Predicting outcome from intensive care for patients with rheumatologic diseases. AB - OBJECTIVE: To evaluate 2 prognostic scoring systems in patients with an underlying rheumatologic diagnosis admitted to an intensive care unit (ICU). METHODS: A retrospective case series review, carried out at a medical ICU in a military referral hospital. All adult ICU admissions with a known rheumatologic diagnosis were evaluated during 28 consecutive months. There were 48 ICU admissions available for review in 36 patients (1.33 ICU admissions/patient) during the study period. All patients were assigned an APACHE II and TISS score based on the first 24 h of ICU admission. RESULTS: Eleven ICU admissions resulted in patient death (22.9%) and the remaining 37 admissions (77.1%) in patient survival and hospital discharge. Overall patient mortality was 30.6% for the study population. The APACHE II and TISS scores were each significantly different for survivor and nonsurvivor subgroups (APACHE II p less than 0.0001; TISS p less than 0.0001). CONCLUSIONS: In this group of patients evaluated at a single institution both the APACHE II and TISS scoring systems allowed subgroup separation between survivors and nonsurvivors of ICU admission. However, these scoring methods demonstrated limitations in terms of outcome prediction when applied to the individual patient. PMID- 1404163 TI - Secondary avascular necrosis in coxarthrosis: a morphologic study. AB - Secondary subarticular avascular necrosis was observed grossly in 11.7% of femoral heads removed surgically because of osteoarthritis (OA). In most cases the necrosis was superficial, however in 15% of the 82 cases of secondary necrosis the necrosis was deep and wedge shaped similar in appearance to the lesions seen in primary subarticular avascular necrosis. Most of the lesions were seen in the early stage of OA and it is suggested that the lesion may interfere with the subsequent reparative phenomenon. PMID- 1404164 TI - HLA antigens in primary fibromyalgia syndrome. AB - HLA antigens, both class I (A,B,C) and II (DR), were determined in 60 patients with primary fibromyalgia syndrome and compared to 159 healthy controls. No significant association between primary fibromyalgia syndrome and alleles of the HLA system was detected. PMID- 1404165 TI - The arthropathy of hereditary arthroophthalmopathy (Stickler syndrome). AB - Hereditary arthroophthalmopathy (Stickler syndrome) is an autosomal dominant syndrome characterized by musculoskeletal, ophthalmic and dysmorphic facial features. A family is described illustrating diverse expressions of Stickler syndrome, including abnormalities not directly attributable to mutation of the type II procollagen gene. A review of the literature demonstrates a range of articular problems, several of which are not specific to Stickler syndrome, and might be encountered in either adult or pediatric rheumatology practice. Stickler syndrome may be underrecognized by rheumatologists, particularly if the significance of nonarticular clinical features or a positive family history are not appreciated. PMID- 1404166 TI - A nutritional screening test for use in children and adolescents with juvenile rheumatoid arthritis. AB - Protein-energy malnutrition (PEM) has been demonstrated in about 35% of patients with juvenile rheumatoid arthritis (JRA), but fewer than 8% of children with rheumatic diseases were reported in a national survey to have been seen by a pediatric dietitian. We demonstrate the development of a nutritional screening test for PEM in patients with JRA for use by all health care professionals. Nutritional assessment of 74 patients with JRA was conducted using a standardized 11 variable profile comprised of upper body anthropometric and biochemical measurements. The sensitivity, specificity, predictive values and index of validity were calculated for individual and selected clusters of nutritional variables to predict the need for referral for PEM compared to the independent review by 2 pediatric dietitians to refer or not refer to a dietitian for further evaluation or care. Arm circumference less than or equal to 10th percentile for age and sex matched norms was selected as the screening test for PEM in patients with JRA due to a combination of excellent measurement characteristics (sensitivity 0.80, specificity 0.86, positive predictive value 0.90, negative predictive value 0.73, index of validity 0.88) and ease of measurement. PMID- 1404167 TI - SEA syndrome revisited: a longterm followup of children with a syndrome of seronegative enthesopathy and arthropathy. AB - Thirty-six of the 39 children originally described with the syndrome of seronegative enthesopathy and arthropathy, followed for a mean of 11 years after symptom onset, were found to have had a widely varied clinical course. Twelve of the 23 patients (52%) who originally did not have a seronegative spondyloarthropathy developed definite (6) or possible (6) seronegative spondyloarthropathies. The development of a seronegative spondyloarthropathy was associated with HLA-B27 (p = 0.0004) and the presence of arthritis (rather than arthralgia only) at the time of the original report (p = 0.05). For patients with arthritis, the development of a seronegative spondyloarthropathy was associated with arthritis onset after 5 years of age (p = 0.01). PMID- 1404168 TI - Primary antiphospholipid syndrome with multiorgan arterial and venous thromboses. AB - A 57-year-old man with no evidence of infection, vasculitis or connective tissue disease died with multiple organ thromboses after an acute illness. He was found to have lupus anticoagulant, IgG anticardiolipin antibody, false positive rapid plasma reagin, prolonged partial thromboplastin time, and thrombocytopenia. Venous and arterial thrombi leading to necrosis were found in his scrotum, testicles, upper and lower extremities, adrenals, kidneys, lungs, and brain. No other explanation could be found for his fatal illness, thus suggesting the primary antiphospholipid syndrome (APS). This is a documented case of primary APS associated with multiorgan arterial and venous thromboses of large and small vessels, presenting as a fulminant and fatal acute illness. PMID- 1404169 TI - Intracardiac mural thrombus mimicking atrial myxoma in the antiphospholipid syndrome. AB - A wide spectrum of cardiac involvement including valvular lesions, myocardial infarction and myocardial dysfunction has been reported in patients with antiphospholipid antibodies (aPL), suggesting that cardiac manifestations may be part of the antiphospholipid syndrome (APS). We describe 3 patients (2 with primary APS and one with APS and SLE) who were found to have right atrial masses by echocardiography (transthoracic and/or transesophageal) and/or angiography, which were felt preoperatively to be atrial myxomata. Pathological examination of resected material showed only organized thrombus with calcification. We describe outcome 12 months to 7 years after resection of thrombus and document possible recurrence in one patient after 7 years. Intracardiac mural thrombus may be an additional cardiac manifestation of the APS, and presents considerable diagnostic confusion in its differentiation from atrial myxomata. PMID- 1404170 TI - Communicating hydrocephalus in systemic lupus erythematosus with antiphospholipid antibody syndrome. AB - We report a case of communicating hydrocephalus in a 24-year-old woman with previously undiagnosed systemic lupus erythematosus (SLE) presenting with malignant hypertension, nephritis, serositis, and a seizure disorder of 16 months' duration. The patient demonstrated features of the antiphospholipid antibody syndrome (APS). In proposing cerebral venous thrombosis as a possible, yet unproven, pathophysiologic mechanism for the hydrocephalus in this case we have reviewed and summarized literature relating to SLE, APS, hydrocephalus and pseudotumor cerebri. In cases of unexplained pseudotumor cerebri or hydrocephalus, a search for SLE and APS should be considered. PMID- 1404171 TI - Systemic lupus erythematosus presenting with myelofibrosis. AB - The 20-year-old girl we describe presented with myelofibrosis and systemic lupus erythematosus (SLE), which initially responded to treatment with corticosteroids but during a relapse 9 months later a bone marrow biopsy revealed no improvement in her myelofibrosis. As the cytotoxic treatments used to treat severe SLE may be associated with bone marrow suppression, it is important to consider the possibility of myelofibrosis complicating SLE, which, even when it is a presenting feature, may not readily respond to corticosteroids. When this girl was subsequently treated with high dose steroid and azathioprine her myelofibrosis went into remission. PMID- 1404172 TI - Streptococcus pyomyositis occurring in a patient with dermatomyositis in a country with temperate climate. AB - We describe a man in whom pyomyositis developed in a temperate climate. Three facts make this case unique. First the pyomyositis developed in someone with underlying dermatomyositis, this being the second reported case to our knowledge. Second, the organism involved was a Streptococcus and not a Staphylococcus as in most cases described, and the course of the disease was acute and not subacute as is usually reported. Finally, contrary to most described cases, surgical drainage was not necessary, probably because of the early diagnosis. Pyomyositis should be considered a possible cause of localized pain in patients with underlying inflammatory muscle disease. PMID- 1404173 TI - Concurrent temporal arteritis and Churg-Strauss syndrome. AB - We describe the case of a 41-year-old man who presented with clinical and histopathologic evidence of temporal artery lesions associated with the Churg Strauss syndrome. Pathological examination of the temporal artery showed panarteritis without giant cell formation or fibrinoid necrosis. We review the world literature concerning the vasculitides with features that overlap giant cell arteritis (GCA) and polyarteritis nodosa (PAN) and classify into 2 sub groups PAN with unusual temporal artery localization and GCA with variably disseminated arterial injuries. These cases emphasize the fact that not all arteritis involving the temporal arteries is GCA. Only 3 cases with temporal artery involvement and concurrent Churg-Strauss syndrome have been published. PMID- 1404174 TI - Computed tomography of the temporomandibular joint in rheumatoid arthritis. PMID- 1404175 TI - Prevalence of antithyroid antibody in patients with systemic lupus erythematosus. PMID- 1404176 TI - Human chorionic gonadotrophin and active ankylosing spondylitis. PMID- 1404177 TI - Ewing's sarcoma of the ilium mimicking an infectious sacroiliitis. PMID- 1404178 TI - Methotrexate induced early onset pancytopenia in rheumatoid arthritis: drug allergy? Idiosyncrasy? PMID- 1404179 TI - Methylprednisolone pulse therapy as primary management strategy in systemic lupus erythematosus. PMID- 1404180 TI - Anticardiolipin antibody syndrome. PMID- 1404181 TI - Atypical Cogan's syndrome in a 76-year-old woman. PMID- 1404182 TI - Rheumatic fever. PMID- 1404183 TI - Medical education and substance abuse. PMID- 1404184 TI - Philosophy of medicine: alternative or scientific. PMID- 1404185 TI - General practice in the post-Morgagni era. PMID- 1404186 TI - Don't jump the queue. PMID- 1404187 TI - General practitioners' use of non-steroidal anti-inflammatory drugs in Tayside and Fife regions. AB - The objectives of this study were to assess the prescribing of non-steroidal anti inflammatory drugs (NSAIDs) by general practitioners and to determine their attitudes to problems caused by this class of drugs. The study consisted of two parts. The first was a questionnaire survey among general practitioners in Fife and Tayside, and the second was an analysis of NSAID prescribing over 12 months among the doctors in the Carnoustie Health Centre, using duplicate prescriptions. In the questionnaire survey 61% of the general practitioners responded. The three most preferred drugs were buprofen (56%), naproxen (20%) and mefenamic acid (7%); choice of drug was determined by efficacy and personal experience. Gastrointestinal side effects were most frequently encountered, although there was little consensus amongst respondents as to their management. The duplicate prescription study showed that 14% of patients (1607 individuals) received at least one NSAID prescription in the year of study. Ibuprofen (31%), naproxen (20%) and piroxicam (15%) were most frequently prescribed and up to 16% of the patients were co-prescribed a gastroprotective agent; ranitidine (75%) was the most commonly prescribed. Despite the introduction of newer NSAIDs, ibuprofen and naproxen are still the most commonly prescribed drugs. Furthermore, although gastrointestinal side effects are commonly encountered, there is some uncertainty about their management. PMID- 1404189 TI - Cerebellar ataxia in the elderly. AB - In a retrospective study of 624 elderly patients referred with falls and gait disorders, 45 patients were found to have ataxia. Cerebrovascular diseases were the most common underlying cause of ataxia (15 patients, 37%). Nine patients had hereditary/degenerative cerebellar ataxia. History suggesting alcohol as an underlying cause was established in two patients with cerebellar ataxia. Three patients had normal pressure hydrocephalus and their condition improved remarkably after surgery. No definite cause was found in five patients. Cranial computed tomography (CT) showed cerebral atrophy in 16 patients and in three patients there was evidence of atrophy of the cerebellar vermis. Four patients had femoral neck fractures and three patients had other fractures. In a 5-year follow-up five patients died with bronchopneumonia (11% mortality) and patients with dementia showed rapid deterioration. All patients were referred to the day hospital for rehabilitation. The best treatment outcome was achieved in patients who had a single cerebrovascular accident with no cognitive impairment and in those whose ataxia was secondary to medication. Fourteen patients (44%) moved to residential care while 27 (66%) continued to live in their homes with community support. We concluded that there is no evidence of increased mortality in the elderly patients with cerebellar ataxia. CT scan is mainly helpful in diagnosing specific diseases such as tumours or hydrocephalus. A significant proportion of elderly patients with ataxia may have reversible or treatable conditions and can pursue an independent life. PMID- 1404188 TI - Prevalence of mitral valve prolapse in keratoconus patients. AB - Fifty patients with advanced degrees of keratoconus, requiring corneal transplantation, were screened for mitral valve prolapse by two dimensional echocardiography. The overall prevalence of 58% was found to be statistically higher than the prevalence of 7% found in a group of age and sex-matched controls. It was also found to be higher than the previously reported prevalence of 38% in a group of keratoconus patients with similar age and sex match to our series. The findings of our study in conjunction with the histopathological and biochemical similarities between the two conditions strongly suggest that they may be different manifestations of similar defects in collagen metabolism. PMID- 1404190 TI - Cardiopulmonary resuscitation training revisited. AB - The cardiopulmonary resuscitation (CPR) skills of 50 junior hospital doctors (22 house officers and 28 senior house officers) were assessed. Theoretical knowledge was measured by a multiple choice questionnaire and practical ability with the Laerdal Skillmeter Resusci Anne. Only 40% of the study group passed both tests. Those doctors who had previously received regular CPR training performed better in the practical test (P<0.05) than those who had not. Theoretical knowledge was unrelated to previous CPR training. It is recommended that junior hospital doctors should undergo regular CPR training every 6 months, in order to maintain their practical CPR skills. PMID- 1404191 TI - Loco-regional recurrence and survival after wide local excision, radiotherapy and axillary clearance for early breast cancer. AB - After breast conservation for early breast cancer which comprised wide local excision, axillary clearance and radiotherapy to the breast, 145 women have been followed prospectively for a median of 42 months. Local recurrence occurred in 11 (7%) and axillary recurrence in three (2%). Distant recurrence has occurred in 32 and accounted for 80% of all first recurrences. Local treatment failure has occurred in three women and would not have been prevented by mastectomy. Loco regional recurrence in the absence of preceding or synchronous distant disease was unusual and did not pose a significant clinical problem. PMID- 1404192 TI - Nail-biting in the population and its relationship to irritable bowel syndrome. PMID- 1404193 TI - Splenic rupture and infectious mononucleosis-splenectomy, splenorrhaphy or non operative management? PMID- 1404194 TI - Dental enamel growth, perikymata and hypoplasia in ancient tooth crowns. AB - This paper describes the hypoplastic defects commonly seen on the surface of ancient human tooth crowns, excavated from archaeological sites, and presents a new method for estimating the ages at which these defects were initiated during life. The method is based upon examination of microscopic incremental structures on the enamel surface and it is possible also to apply it to reconstruction of the sequence and timing of dental crown development. The method of examination is non-destructive and allows full use to be made of the large numbers of complete, unworn dentitions which are found amongst archaeological remains. PMID- 1404195 TI - The results of examinations of serious sexual offences: a review. PMID- 1404196 TI - Addiction: treatment and outcome. PMID- 1404197 TI - Which treatments work for alcohol-related problems. PMID- 1404198 TI - Barriers to education about alcohol. PMID- 1404199 TI - Primary care physicians and alcohol. PMID- 1404201 TI - Jeremy Schrecker's Life Spring and Bedrock at Hammersmith Hospital. A patient's poem. PMID- 1404200 TI - A structure for psychiatry at the century's turn--the view from Johns Hopkins. PMID- 1404202 TI - Medicine in San'a, Yemen 1937-1943. PMID- 1404203 TI - Hurthle cell carcinoma presenting with retroorbital metastasis. PMID- 1404204 TI - Dysthyroid eye disease with radiological features of orbital tumour. PMID- 1404205 TI - Haematological improvement with conservative management in an infant with myelodysplasia. PMID- 1404206 TI - Tendon contractures in hypercholesterolaemia. PMID- 1404207 TI - Familial precocious puberty in girls. PMID- 1404208 TI - Milk-alkali syndrome due to Caved-S. PMID- 1404209 TI - Acute angle closure glaucoma occurring after nebulized bronchodilator treatment with ipratropium bromide and salbutamol. PMID- 1404210 TI - Simultaneous temporal lobe and cerebellar abscess complicating acute otitis media. PMID- 1404211 TI - Benzodiazepines in anxiety management. PMID- 1404212 TI - Age changes in the teeth. PMID- 1404213 TI - Breast cancer and liver metastases--incidence, diagnosis and outcome. PMID- 1404214 TI - Alvarado score and acute appendicitis. PMID- 1404215 TI - Measurement of HDL cholesterol. PMID- 1404216 TI - Assisting the police with their enquiries. PMID- 1404217 TI - Treatment of glue ear by postural drainage. PMID- 1404219 TI - Inferior turbinates. PMID- 1404218 TI - Brown bowel syndrome associated with chronic oesophagitis and oesophageal stricture. PMID- 1404220 TI - Functional anatomy of the penguin flipper. AB - This study investigates the functional anatomy of the flipper of the jackass penguin (Speniscus demersus). The flippers of birds (n = 15) were dissected and described. Several adaptations from the typical avian wing were noted and reasons were proposed for these. The conclusion is that the osteological and myological adaptations of the flipper are designed to enable the penguin to progress very effectively through water, while the vascular adaptations provide a highly efficient mechanism for thermoregulation. PMID- 1404221 TI - A qualitative study of the attitudes of members of a developing community towards their dogs and veterinary services. AB - A university-based hospital serving mainly a developing community readily appreciated that its clientele was from a very different sociological and cultural background than that of the professional staff and that developed and developing communities and their pets exhibit different patterns in their health status, with most diseases being predominantly related to socio-economic predicament. The need for a community-orientated service was recognised. From 1987 to 1988, the small animal outpatient clinic was used for an informal, unstructured sociological observation and interview-based study of the clientele and their pets. During this period, an informal educational programme was implemented to teach basic pet health care, and the efficacy of this programme was empirically gauged by comparing the knowledge and attitudes of first-time clients with those of regular clients. Regular clients appeared to become increasingly concerned about the health and management of their pets and the condition of their animals appeared to improve, with a corresponding decline in the degree of parasitism. The majority of clients however, still regarded the main reason for keeping dogs as the provision of some form of security. It also appeared as if improved attitudes towards household pets paralleled improvements in socio-economic status. PMID- 1404222 TI - Tick control on cattle with flumethrin pour-on through a Duncan Applicator. AB - Cattle were treated for tick infestation using 1% flumethrin pour-on applied through a self-medicating device known as the Duncan Applicator, in 4 situations in Zimbabwe. Moderate to heavy tick infestations were successfully controlled on cattle. PMID- 1404224 TI - Anaplastic tracheal squamous cell carcinoma in a cat. AB - A cat with primary intratracheal squamous cell carcinoma presented with severe dyspnoea and a dry cough. Radiographic changes included pulmonary hyperinflation and tracheal thickening at the thoracic inlet. On post mortem examination, proliferative, white, granular nodules in the trachea were confirmed to be an anaplastic squamous cell carcinoma. PMID- 1404223 TI - The diagnosis and treatment of bovine genital ureaplasmosis: a case study. AB - An outbreak of granular vulvitis and ulcerative posthitis in 24-month-old virgin Bonsmara heifers and bulls is reported. Ureaplasma was isolated locally from all the clinically infected cattle. There was marked clinical improvement within 3 d of the commencement of a 5 d course of tylosin administered intramuscularly at 10 mg kg-1. Ureaplasma could not be cultured from the external genitalia of either heifers or bulls following clinical recovery. Details of the Ureaplasma culture media are given. PMID- 1404225 TI - Clinical and biochemistry findings, and parathyroid hormone concentrations in three horses with secondary hyperparathyroidism. AB - Three cases of horses with nutritional secondary hyperparathyroidism (NSH) are described. The horses showed typical thickening of the maxillae and mandibular bones with or without lameness. Laboratory findings included elevated concentrations of parathyroid hormone (carboxy-terminal and mid-molecule fractions), alkaline phosphatase and an increase in the fractional excretion rate of serum inorganic phosphorus. PMID- 1404226 TI - Synthesis and antimalarial properties of 1-imino derivatives of 7-chloro-3 substituted-3,4-dihydro-1,9(2H,10H)-acridinediones and related structures. AB - To improve upon the activity and properties of the 3-aryl-7-chloro-3,4- dihydro 1,9(2H,10H)-acridinediones, a variety of 1-[(alkylamino)alkylene]imino derivatives (3) were prepared and shown to be highly active antimalarial agents in both rodents and primates. Among structural modifications prepared, including N10-alkyl and C2-substituted analogs, removal of the C9 oxygen, and introduction of an imino side chain at C9, the imines of the N10-H acridinediones were the most active compounds obtained. The [3-(N,N- dimethylamino)propyl]imino derivative of 7-chloro-3-(2,4-dichlorophenyl)-3,4-dihydro-1,9(2H,10H)- acridinedione (9aa) proved to be highly active in advanced studies in primates. PMID- 1404227 TI - Acyclic analogues of lipid A: synthesis and biological activities. AB - The synthesis of a series of novel acyclic analogues of lipid A, the lipophilic terminal of lipopolysaccharide (LPS), is reported. In these compounds, the reducing glucose unit of lipid A has been replaced by an acyclic analogue unit (abbreviated as AAU) consisting of a spacer (of varying length), an (R)-3 hydroxytetradecanamido moiety (of varying configuration at the carbon of attachment), and a CO2H group. The AAU has been attached to the anomeric carbon of the nonreducing glucose unit of lipid A, either through glycosidic linkage or through an acyl linkage. Further, amide isosteres of these acyclic analogues have been prepared using suitably protected 2,3-diamino-2,3-dideoxyglucose instead of 2-amino-2-deoxyglucose. All the compounds were well characterized and were tested for their ability to induce TNF-alpha in mouse bone marrow-derived macrophages, to enhance nonspecific resistance to infection in mice and to induce endotoxic shock in mice. The results showed a dramatic dependence, for the first time, on the length of the spacer and on the configuration of the carbon bearing the amido group in the AAU part of the analogues. PMID- 1404228 TI - Synthesis and antibacterial activity of 1-(substituted pyrrolyl)-7-(substituted amino)-6-fluoro-1,4-dihydro-4-oxo-3- quinolinecarboxylic acids. AB - Seventeen quinolone compounds characterized by having a fluorine atom at the 6 position, a substituted amino at the 7-position, and a substituted pyrrolyl at the 1-position were synthesized for the first time. The in vitro antibacterial activities of these compounds against Escherichia coli and Staphylococcus aureus were tested. Among these agents obtained, compound 24 showed significantly enhanced activity against S. aureus. The results indicate that there is much room for modifications at the N-1 position. PMID- 1404229 TI - Development, synthesis, and biological evaluation of (-)-trans-(2S,5S)-2-[3-[(2 oxopropyl)sulfonyl]-4-n-propoxy-5-(3- hydroxypropoxy)-phenyl]-5-(3,4,5 trimethoxyphenyl)tetrahydrofuran, a potent orally active platelet-activating factor (PAF) antagonist and its water-soluble prodrug phosphate ester. AB - (-)-trans-(2S,5S)-2-[3-[(2-Oxopropyl)sulfonyl]-4-n-propoxy-5-(3- hydroxypropoxy)phenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (10) is one of the most potent platelet-activating factor (PAF) antagonists in vitro and in vivo developed to date. This diaryltetrahydrofuran derivative evolved from modifications of MK 0287 which has been evaluated in clinical studies for asthma. Two structural modifications of MK 0287 were made: (1) elaboration of the 3' [(hydroxyethyl)sulfonyl] group to a beta-keto propylsulfonyl, and (2) replacement of the 5'-methyl ether by a 3-hydroxypropyl ether. Compound 10 potently and specifically inhibits the binding of [3H]-C18-PAF to human platelet membranes (Ki 1.85 nM) and PMN membranes (Ki 2.89 nM). In vivo, 10 inhibits PAF-induced plasma extravasation and elevated N-acetyl-beta-D-glucosaminidase (NAGA) levels in male rats with ED50 values of 60 micrograms/kg, po and 4 micrograms/kg, iv respectively, and inhibits PAF-induced bronchoconstriction in guinea pigs with an ED50 value of 15 micrograms/kg after intraduodenal administration. Compound 15, a water-soluble phosphate ester prodrug derivative of 10 is at least equipotent to 10 in the in vivo models. Compound 19S, the primary and major metabolite of 10 and 15, is equipotent in in vitro and in vivo models. PMID- 1404230 TI - Nonprostanoid prostacyclin mimetics. 2. 4,5-Diphenyloxazole derivatives. AB - 4,5-Diphenyl-2-oxazolenonanoic acid (18b) was synthesized and found to inhibit ADP-induced aggregation of human platelets with an IC50 of 2.5 microM. Acid 18b displaced [3H]iloprost from human platelet membranes in a concentration-dependent fashion, consistent with 18b inhibiting platelet function by acting as a prostacyclin mimetic. By inserting a phenoxy ring into the side-chain moiety of 18b and systematically varying the pattern of substitution and length of the tethers, more potent inhibitors of platelet aggregation were identified. A phenoxy ring inserted centrally in the side chain proved to be the optimal arrangement but significant activity was observed when the aromatic ring was bound directly to the 2 position of the heterocycle. The meta-substituted cis (ethenylphenoxy)acetic acid 37 is the most potent platelet aggregation inhibitor synthesized as part of this study with an IC50 of 0.18 microM. Acid 37 displaces [3H]iloprost from human platelet membranes with an IC50 of 6 nM. The trans olefinic isomer of 37 (25p) is 72-fold weaker as an inhibitor of ADP-induced platelet aggregation, but the saturated derivative 25w (BMY 42393) is intermediate in potency. Structure-activity studies using 25w as a template focused on modification of the tethers intervening between the side-chain phenyl ring and the oxazole and carboxylate termini and substitution of the phenyl ring. These studies revealed that biological activity was sensitive to both the identity of the concatenating atoms and the pattern of ring substitution. The structure-activity relationships provide insight into the topographical relationship between the diphenylated oxazole ring and the carboxylic acid terminus that comprise the nonprostanoid prostacyclin mimetic pharmacophore. PMID- 1404231 TI - Nonprostanoid prostacyclin mimetics. 3. Structural variations of the diphenyl heterocycle moiety. AB - 4,5-Diphenyl-2-oxazolenonanoic acid (2) and 2-[3-[2-(4,5-diphenyl-2 oxazolyl)ethyl]phenoxy]acetic acid (3) were previously identified as nonprostanoid prostacyclin (PGI2) mimetics that inhibit ADP-induced aggregation of human platelets in vitro. The effects on biological activity of substitution and structural modification of the 4- and 5-phenyl rings of 3 was examined. Potency showed a marked sensitivity to the introduction of substituents to these aromatic rings and only the bis-4-methyl derivative 9j, IC50 = 0.34 microM, demonstrated enhanced potency compared to the parent structure 3, IC50 = 1.2 microM. Substitution at the ortho or meta positions of the phenyl rings, replacement by thiopheneyl or cyclohexyl moieties, or constraining in a planar phenanthrene system resulted in compounds that were less effective inhibitors of ADP-induced platelet aggregation. In contrast, variation of the heterocycle moiety revealed a much less stringent SAR and many 5- and 6-membered heterocycles were found to effectively substitute for the oxazole ring of 2 and 3. The diphenylmethyl moiety functioned as an effective isostere for 4,5-diphenylated heterocycles since 13aad showed similar platelet inhibitory activity to 3. With the exception of the 3,4,5-triphenylpyrazole derivative 13g, compounds presenting the (m-ethylphenoxy)acetic acid side chain discovered with 3 demonstrated enhanced potency compared to the analogously substituted alkanoic acid derivative. The structure-activity findings led to a refinement of a model of the nonprostanoid PGI2 mimetic pharmacophore. PMID- 1404232 TI - Flavones. 3. Synthesis, biological activities, and conformational analysis of isoflavone derivatives and related compounds. AB - A series of 2-alkylisoflavone derivatives 1 was prepared with the intent to study the importance of the phenyl group (at the 3-position) of the isoflavone in imparting antihypertensive activity and the substitution effects at the 2 position of isoflavone. With the exception of the 2-isopropyl analog, the antihypertensive activity of these compounds appears to have a slow onset and long duration. None of the analogs appears better than the corresponding flavone (3) and 3-phenylflavone (2) analogs. An unsuccessful attempt to correlate the relationship between antihypertensive activity and the calculated torsional angle of C2-C3-C1'-C2' is discussed. Antiinflammatory activities of these compounds along with 7-(oxypropylamine)flavones were also evaluated and found to be not very potent. The antiinflammatory activity appears to be sensitive to steric effects of the alkyl group on the nitrogen and of substituents at the 2-position of the isoflavones, while the hydroxyl group of the propanolamine side chain is not essential. PMID- 1404233 TI - Renin inhibitors containing new P1-P1' dipeptide mimetics with heterocycles in P1'. AB - A series of renin inhibitors containing new P1-P1' dipeptide mimetics are presented. The P1-P1' mimetics were obtained from (4S,5S)-3-(tert-butoxycarbonyl) 4-(cyclohexylmethyl)-5-[(omega- mesyloxy)alkyl]-2,2-dimethyloxazolidines 5b, 9, and 11b by nucleophilic substitution of the mesylate groups with the sodium salts of mercapto- and hydroxyheterocycles. Removal of the protecting groups and stepwise acylations with amino acid derivatives provided renin inhibitors with a length of a tripeptide. Replacement of P2 histidine by other amino acids maintained or enhanced renin inhibitory potency. By alteration of P3 phenylalanine, compounds with IC50 values in the nanomolar range and stability against chymotrypsin were obtained. Finally, the effect of the C-terminal heterocycle on the renin inhibition was studied. Compound XVII was examined in vivo for its hypotensive effects. In salt-depleted cynomolgus monkeys, XVII inhibited plasma renin activity and lowered blood pressure after oral administration of a dose of 10 mg/kg. PMID- 1404234 TI - 6-Alkyl-12-formylindolo[2,1-a]isoquinolines. Syntheses, estrogen receptor binding affinities, and stereospecific cytostatic activity. AB - A number of 6-alkyl-12-formyl-5,6-dihydroindolol[2,1-a]isoquinolines were synthesized by the Bischler-Napieralski reaction from the respective 1-alkyl-2-(3 methoxyphenyl)ethylamines and bromo-substituted (methoxyphenyl)acetic acid chlorides followed by a second ring closure reaction involving a base-generated benzyne intermediate. The methoxy functions in positions 3 and 9 or 10 were cleaved with BBr3 and the free hydroxy groups converted into the acetates. The enantiomers of the most potent derivatives were separated by liquid chromatography on triacetylcellulose. All of the compounds tested bind to the calf uterine estrogen receptor. The relative binding affinities (RBA) ranged from 0.5 to 3.9 (17 beta-estradiol: RBA = 100) and were dependent on the position of the oxygen function in the indole moiety. The 3,10-diacetoxy derivatives showed higher RBA values than the corresponding 3,9-substituted tetracycles. There was no major difference in binding affinity between (+)- and (-)-enantiomers. Computer-assisted molecular modeling studies showed that the chiral carbon atom 6 of the indoloisoquinoline is likely to mimic the C-11 atom of estradiol. In the mouse uterine weight test, only the 3,10-diacetoxy series exhibited weak estrogenic activity at higher doses. The antiestrogenic effects found with all the compounds varied considerably. Maximum inhibition of estrone-stimulated uterine growth was found for the ethyl derivative 7d (80% with 250 micrograms/animal per day). All derivatives strongly inhibited the growth of human breast cancer cells in vitro. There was no significant difference between hormone-sensitive MCF-7 cells and hormone-independent MDA-MB 231 cells. Cytostatic activity was higher for the 3,9-substituted indoloisoquinolines than for the 3,10-analogues and dependent on the length of the alkyl group at C-6. The maximum effect was found with the butyl derivative 7g. When the enantiomers of the ethyl (7c), propyl (7e), and butyl derivative were studied, a strong difference in activity was observed between the stereoisomers. The IC50 values of the (+)-forms were usually only a tenth of those of the levorotatory isomers. Maximum cytostatic activity was found with (+)-7g: 85% inhibition at 1 x 10(-7) M in MCF-7 cells and 94% inhibition at 2.5 x 10(-7) M in MDA-MB 231 cells. This stereospecificity indicates a selective action on a biochemical target. Since no interaction with DNA was observed, the precise mode of action still remains to be elucidated. PMID- 1404235 TI - 6-substituted decahydroisoquinoline-3-carboxylic acids as potent and selective conformationally constrained NMDA receptor antagonists. AB - We have prepared a series of 6-substituted decahydroisoquinoline-3-carboxylic acids, and structurally similar analogs, as potential N-methyl-D-aspartate receptor antagonists. There is a large body of evidence to support the use of such compounds as cerebroprotective agents in a variety of acute and chronic neurodegenerative disorders, where some component of glutamate-mediated excitotoxicity may exist. The compounds prepared were evaluated in vitro in both receptor binding assays ([3H]CGS19755, [3H]AMPA, and [3H]kainic acid) and in a cortical wedge preparation (versus NMDA, AMPA, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced lethality in mice. We synthesized many of the possible diastereomers of the decahydroisoquinoline nucleus in order to examine the spatial and steric requirements for affinity at the NMDA receptor and activity as NMDA antagonists. From our structure-activity relationship we identified two potent and selective NMDA receptor antagonists, the phosphonate- and tetrazole-substituted amino acids 31a and 32a, respectively, that show good activity in animals following systemic administration. For example, 31a and 32a selectively displaced [3H]CGS19755 binding with IC50S of 55 +/- 14 and 856 +/- 136 nM, respectively, and selectively antagonized responses due to NMDA in a cortical wedge preparation with IC50S of 0.15 +/- 0.01 and 1.39 +/- 0.29 microM, respectively. And compounds 31a and 32a blocked NMDA-induced lethality in mice with minimum effective doses of 1.25 and 2.5 mg/kg (intraperitoneal), respectively. These novel amino acids are among some of the most potent NMDA antagonists described thus far, and are excellent candidates for development as neuroprotective agents for a number of CNS disorders. PMID- 1404236 TI - 5,5-disubstituted hydantoins: syntheses and anti-HIV activity. AB - A series of 5,5-disubstituted hydantoin derivatives was synthesized by alkylating 5,5-bis(mercaptomethyl)-2,4-imidazolidinedione (3) with various halomethylaromatic or halomethylheteroaromatic precursors, or by using the Buchener-Berg procedure on the required ketone. When evaluated for their ability to inhibit HIV-induced cell killing and virus production in CEM or MT-2 cells only compounds 2, 4n, 4o, and 4i demonstrated modest activity, the latter with an IC50 = 53 microM. PMID- 1404237 TI - 2-Nitroimidazole dual-function bioreductive drugs: studies on the effects of regioisomerism and side-chain structural modifications on differential cytotoxicity and radiosensitization by aziridinyl and oxiranyl derivatives. AB - A series of 2-nitroimidazoles bearing side chains terminating in or containing aziridinyl and oxiranyl groups has been prepared, and the compounds were evaluated in vitro as hypoxia-selective bioreductively-activated cytotoxins and selected compounds tested for their radiosensitizing properties toward hypoxic mammalian cells. Compounds were either the regioisomers of analogues of the potent dual-functional 2-nitroimidiazole alpha-[(1-aziridinyl)-methyl]-2-nitro-1H imidazole-1- ethanol (RSU-1069, 1) with additional methyl groups or related oxiranes of varying side-chain length and type. Oxiranyl derivatives showed little differential toxicity, and those tested were less effective as radiosensitizers, and although these properties were influenced by side-chain length, differences were not great. Aziridinyl compounds related to 1 but with increased side-chain lengths were unstable. Methylation of 1 in various regions had little effect on radiosensitization and no clear advantages over 1 as differential cytotoxic drugs. Progressive methylation at C-3 was found to increase toxicity but decrease hypoxia selectivity. Incorporation of a cyclohexane side chain in 1,2-cis-2,3-trans-3-aziridin-1-yl-2-hydroxy-1-(2 nitroimidazol+ ++-1- yl)cyclohexane (26) abolished hypoxia-selective toxicity and unexpectedly reduced radiosensitizing efficiency. Of the aziridines, 1-(2-nitro-1 imidazolyl)-2-methyl-3-(1-aziridinyl)-2-propanol (20) was comparable in efficacy to 1 as a bioreductively-activated cytotoxin with slightly lower aerobic toxicity; however, the prodrugs of 1 remain as preferred candidates for clinical evaluation. PMID- 1404238 TI - 7,8-Dihydro-8-ethyl-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one: a potent and water-soluble adenosine A1 antagonist. PMID- 1404239 TI - N-(1-oxododecyl)-4 alpha,10-dimethyl-8-aza-trans-decal-3 beta-ol: a potent competitive inhibitor of 2,3-oxidosqualene cyclase. PMID- 1404240 TI - Fatty acid amides: scooting mode-based discovery of tight-binding competitive inhibitors of secreted phospholipases A2. PMID- 1404242 TI - Oxidant and angiotensin II-induced subcellular translocation of protein kinase C in pulmonary artery endothelial cells. AB - We recently reported that nitrogen dioxide (NO2), an environmental oxidant, alters the dynamics of the plasma membrane lipid bilayer structure, resulting in increased phosphatidylserine content and angiotensin II (Ang II) receptor binding. Angiotensin II is known to elicit receptor-mediated stimulation of diacylglycerol (DAG) production in pulmonary artery endothelial cells. Because protein kinase C (PKC) is a phosphatidylserine-dependent enzyme and is activated by DAG, we examined whether NO2 resulted in activation and/or translocation of PKC from predominantly cytosolic to membrane fractions of these cells. We also evaluated whether NO2 exposure resulted in increased production of DAG in pulmonary artery endothelial cells. Exposure to 5 ppm NO2 for 1-24 hr resulted in significant increases in PKC activity in the cytosolic and membrane fractions (p less than 0.05 for both fractions) compared to activities in control fractions. Exposure to Ang II resulted in translocation of PKC activity from cytosol to membrane fractions of both control and NO2-exposed cells. This translocation of PKC from cytosolic to membrane fraction was prevented by the specific receptor antagonist [Sar1 Ile8] Ang II. Exposure of 5 ppm NO2 for 1-24 hr provoked rapid increases in [3H]glycerol labeling of DAG in pulmonary artery endothelial cells. These results demonstrate that exposure to NO2 increases the production of second messenger DAG and activates PKC in both the cytosolic and membrane fractions, whereas Ang II stimulates the redistribution of PKC from cytosolic to membrane fractions of pulmonary artery endothelial cells. PMID- 1404241 TI - TCDD causes stimulation of c-ras expression in the hepatic plasma membranes in vivo and in vitro. AB - A series of in vivo and in vitro experiments were conducted to determine the effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) administered on the expression of c-ras. Differences in c-ras expression between control and TCDD treated groups were determined by immunoassay of p21ras protein, or indirectly measured by the specific binding of 3H-GTP to hepatic plasma membrane preparations. Intraperitoneal injection of sublethal doses of TCDD significantly elevated (P less than 0.05, Student t test) levels of hepatic p21ras protein in Sprague-Dawley rats and TCDD sensitive C57BL/6J mice. Such an increase occurred at an early stage of poisoning in the C57BL/6J mice. The earliest increase was detectable 6 hr after dosing, and the difference became statistically significant by 12 and 24 hr after dosing. In contrast, TCDD tolerant DBA/2J mice had only a marginal increase in hepatic p21ras protein which did not become statistically significant even at 24 hr host-dosing. TCDD evoked increases in hepatic p21ras protein of C57BL/6J mice were accompanied by the increase in the specific binding of GTP to hepatic plasma membranes. Column chromatography of solubilized rat hepatic membrane proteins on sephadex G-50 showed TCDD administration increased levels of a 3H-GTP binding protein with MW of approximately 21 Kd. 3H-GTP binding in total hepatic membranes was also elevated (P less than 0.05, Fisher PLSD multiple comparison test) 6 hr and 24 hr after dosing of C57BL/6J mice, but as expected the effect of TCDD was not as conspicuous as that found in the plasma membrane. TCDD treatment increased levels of a 21 Kd protein found in the in vitro translation products of RNA purified from guinea pig liver. This protein was identified as a c-ras protein based upon its ability to bind GTP, precipitation by a polyclonal antibody against the rasHa and Ki proteins and subsequent SDS-PAGE which showed a single protein band of approximately 21 Kd. PMID- 1404243 TI - The role of calcium ions for the expression of ricin toxicity in cultured macrophages. AB - Ricin toxin, which consists of two distinct polypeptide moieties, A and B chains, is cytotoxic to the cultured macrophage cell line, J774A.1. Ricin is a protein synthesis inhibitor, and incubating macrophages for 4 hours with ricin (1 pM to 10 nM) in standard medium containing calcium and magnesium inhibited 3H-leucine incorporation into protein (97%, at 1 nM ricin). However, in Ca(2+)-free medium, protein synthesis was inhibited only 19%. EGTA pretreatment (to deplete intracellular calcium) also partly protected cells from protein synthesis inhibition, in spite of added calcium (2 mM) in the incubation medium. Decreased toxicity in the absence of extracellular calcium resulted from decreased toxin binding. Adding or deleting Mg2+ did not affect protein synthesis or binding of 125I-ricin in cultured macrophages. We conclude that calcium is required for ricin to exert its inhibitory effect on protein synthesis in cultured macrophages. PMID- 1404244 TI - Modifiers of mercaptopyruvate sulfurtransferase catalyzed conversion of cyanide to thiocyanate in vitro. AB - The enzyme mercaptopyruvate sulfurtransferase appears to play an important role in the in vivo detoxification of cyanide. It does so by transferring sulfur to cyanide to produce thiocyanate, which is less toxic and may be excreted through the kidney. Several compounds were tested for their ability to affect the rate of enzyme catalyzed thiocyanate formation in vitro. The studies were carried out using both a partially purified bovine kidney extract and a highly purified enzyme preparation. Hypotaurine and methanesulfinic acid doubled sulfurtransferase activity in the partially purified extract at 30 mM, but inhibited the purified enzyme to 57% (hypotaurine) and 27% (methanesulfinic acid) of control activity at the same concentration. Pyruvate, phenylpyruvate, oxobutyrate, and oxoglutarate each inhibited the extract and purified forms of mercaptopyruvate sulfurtransferase. Phenylpyruvate was the most effective inhibitor, reducing activity to 0.2% of control values in the extract, and 11% of control values for purified MPST when added to the reaction at 30 mM. Other compounds tested (see Table 1) had a negligible effect on sulfurtransferase activity. A heat stable cofactor was found in boiled kidney extract which stimulated sulfurtransferase activity in the extract but inhibited sulfurtransferase activity in the purified enzyme, as was observed for hypotaurine and methanesulfinate. The boiled extract had no thiocyanate forming activity of its own. The cofactor operated in synergy with methanesulfinate, but independently of hypotaurine. PMID- 1404245 TI - Biological action of lantadene C, a new hepatotoxicant from Lantana camara var. aculeata. AB - Lantadene C (22 beta-2-methylbutanoyloxy-3-oxoolean-12-en-28-oic acid) isolated from the leaves of the hepatotoxic plant Lantana camara var. aculeata (Red) has been found to be identical with dihydrolantadene A reported earlier. Molecular structure of lantadene C has been deduced from single crystal X-ray diffraction analysis. It resembles lantadene A in the pentacyclic portion of the molecule but differs in the side chain region. Atom C-34 is cis to C-35 in lantadene C but is trans in lantadene A. Semisynthetic lantadene C was prepared by catalytic hydrogenation of lantadene A. Lantadene C was obtained in two forms, I and II. Form I was crystalline while form II was amorphous. Unlike lantadene A, both form I and II of lantadene C elicited strong hepatotoxic response in guinea pigs associated with decrease in fecal output, feed intake, hepatomegaly, hepatic injury at the cellular and subcellular level, increase in plasma bilirubin, and acid phosphatase activity. All the clinical signs, hepatic lesions, and changes in blood plasma typified lantana toxicity. This is the first report on the hepatoxicity of lantadene C. The interrelation of molecular structure and biological activity of lantadene A and C has been discussed. PMID- 1404246 TI - Whether cytochrome P450 induction accompanies glucuronosyl and glutathione transferase induction by isomers of dipyridyl appears unrelated to dose and iron chelation properties. AB - Administration of 4,4'dipyridyl to rats induces the activities of xenobiotic transferases (phase II drug metabolizing enzymes), UDP-glucuronosyl-transferase and glutathione-S-transferase, and also the concentration and activity of cytochrome P450 (a phase I drug metabolizing enzyme). 2,2'Dipyridyl, an isomer possessing iron chelation properties, only induces the phase II enzymes. Although the magnitude of the phase II induction by 2,2'dipyridyl increases with increasing dosages, the selective induction of only phase II activities remains inviolate. Co-administration of 2,2'dipyridyl does not prevent 4,4'dipyridyl from inducing cytochrome P450, suggesting that the iron chelation property is not the factor that precludes 2,2'dipyridyl from coordinately inducing cytochrome P450 with the transferases. PMID- 1404247 TI - Effects of diphenyl ether herbicides on porphyrin accumulation by cultured hepatocytes. AB - Several diphenyl ether herbicides, such as acifluorfen methyl, have been previously shown to cause large accumulations of the heme and chlorophyll precursor, protoporphyrin, in plants. Light-induced herbicidal damage is mediated by the photoactive porphyrin. Here we investigate whether diphenyl ether herbicides can affect porphyrin synthesis in rat and chick hepatocytes. In rat hepatocyte cultures, protoporphyrin, as well as coproporphyrin, accumulated after treatment with acifluorfen or acifluorfen methyl. Combination of acifluorfen methyl with an esterase inhibitor to prevent the conversion of acifluorfen methyl to acifluorfen resulted in a greater accumulation of porphyrins than caused by acifluorfen methyl or acifluorfen alone. In vitro enzyme studies of hepatic mitochondria isolated from rat and chick embryos demonstrated that protoporphyrinogen oxidase, the penultimate enzyme of heme biosynthesis, was inhibited by low concentrations of acifluorfen, nitrofen, or acifluorfen methyl with the latter being the most potent inhibitor. These findings indicate that diphenyl ether treatment can cause protoporphyrin accumulation in rat hepatocyte cultures and suggest that this accumulation was associated with the inhibition of protoporphyrinogen oxidase. In cultured chick embryo hepatocytes, treatment with acifluorfen methyl plus an esterase inhibitor caused massive accumulation of uroporphyrin rather than protoporphyrin or coproporphyrin. Specific isozymes of cytochrome P450 were also induced in chick embryo hepatocytes. These effects were not observed in the absence of an esterase inhibitor. These results suggest that diphenyl ether herbicides can cause uroporphyrin accumulation similar to that induced by other cytochrome P450-inducing chemicals such as polyhalogenated aromatic hydrocarbons in the chick hepatocyte system. PMID- 1404248 TI - Species differences in membrane susceptibility to lipid peroxidation. AB - The susceptibility of liver microsomes to lipid peroxidation was evaluated in seven species: rat, rabbit, trout, mouse, pig, cow, and horse. Lipid peroxidation was measured as thiobarbituric acid reactive substances formed in the presence of either FeCl3-ADP/ascorbate or FeCl2/H2O2 initiating systems. For rat, rabbit, and trout microsomes, the order of susceptibility to peroxidation was rat greater than rabbit much greater than trout. The lack of peroxidation in trout microsomes could be explained by high microsomal vitamin E levels. Membrane fatty acid levels differed between species. Docosahexaenoic acid predominated in the trout, arachidonic acid in the rat, and linoleic acid in the rabbit. The contribution of individual fatty acids to lipid peroxidation reflected the degree of unsaturation with docosahexaenoic greater than arachidonic much much greater than linoleic. For all species except trout, the predicted susceptibility to peroxidation, based on the response of individual fatty acids, agreed well with directly measured microsomal peroxidation. With the exception of the trout, vitamin E content ranged from 0.083-0.311 nmol/mg microsomal protein between species, and low levels did not influence susceptibility to peroxidation. Trout microsomes peroxidized only after vitamin E depletion by prolonged incubation. The data indicate that below a vitamin E threshold, species differences in membrane susceptibility to peroxidation can be reasonably predicted based only on content of individual peroxidizable fatty acids. PMID- 1404249 TI - Changes in population density and distribution of Ixodes dammini (Acari: Ixodidae) in Wisconsin during the 1980s. AB - Changes in the density and distribution of Ixodes dammini, Spielman Clifford, Piesman & Corwin were assessed in Wisconsin by examining hunter-killed deer for ticks in 1981 and 1989. Deer examination sites were distributed widely across the state and included 23 sites in 1981 and 15 sites in 1989; 10 sites were visited both years. Between 1981 and 1989, I. dammini became more abundant throughout its range, and I. dammini range expanded into the southwestern portion of Wisconsin. I. dammini was not found in the eastern one-third of the state. When compared with 1981, the 1989 survey revealed significant increases in the proportion of infested deer in the southwest (Arena), higher levels of infestation of individual deer (number of ticks per individual deer) in the central west (Bangor W. Salem), and significantly less disparity between the proportions of infested male deer and infested female deer in the north (Spooner) compared with sites farther south. These results are consistent with a pattern of I. dammini range expansion from north to south, followed by an increase in population density in the colonized areas. Dermacentor albipictus Packard was present throughout the range of I. dammini and at sites in the northeastern quadrant of Wisconsin where I. dammini was not found. The range of D. albipictus did not change between the survey years, but its population density increased significantly at sites in the north. There is no evidence for interaction between the two tick species that might affect tick distribution or population density, nor can the greater number of I. dammini found in 1989 be attributed to increased tick activity because of warmer weather; temperatures were cooler in 1989 than 1981. PMID- 1404250 TI - Phlebotomine sandflies in Venezuela: review of the verrucarum species group (in part) of Lutzomyia (Diptera: Psychodidae) with description of a new species from Lara. AB - The series townsendi and verrucarum of the verrucarum species group of the phlebotomine genus Lutzomyia Franca are reviewed. Lutzomyia nadiae, new species, from the mountains of Yacambu, Lara State, is described. Distribution maps, illustrated keys, notes on medical importance, taxonomy, and ecology are presented for species in these series known from Venezuela. PMID- 1404251 TI - Survival and vertical distribution of larvae of Culicoides variipennis (Diptera: Ceratopogonidae) in drying mud habitats. AB - The ability of third and fourth instars of Culicoides variipennis (Coquillett) to survive in drying sandy loam soil was tested under simulated field conditions. Two hundred larvae were added to each of a number of soil-filled, plastic tubes, which were buried in the field and retrieved after 2, 5, and 7 d. Of 306 pupae or pupal exuviae recovered, 98.1% were in the top 2 cm of mud. Estimated larval mortality on day two ranged from 25.6 to 87.1% among three trials, and 92.3% of live larvae were in the top 2 cm. Estimated larval mortality on day 5 ranged from 81.4 to 97.2%, and 75.5% of live larvae were in the top 2 cm. On day 7 mortality was 95.2-100%, and 63% of surviving larvae were in the top 2 cm. Some larvae dispersed as deep as 7-10 cm (the maximum depth in the tests). Larval tolerance of unfavorable drying conditions may allow relic populations to persist in some situations, but probably this is of little concern in control of this species through water management in most settings. PMID- 1404252 TI - Laboratory studies on the life cycle of Amblyomma marmoreum (Acari: Ixodidae) on two different hosts. AB - A comparative study was made of the life cycle of the tortoise tick, Amblyomma marmoreum Koch, on tortoises and guinea pigs under laboratory conditions. At 25 degrees C and 85% RH with natural day length, duration of off-host stages (preoviposition, oviposition, incubation, and premolt) was similar for ticks fed on both hosts. Delay in preoviposition (up to 90 d) was observed in some gravid females. Larvae, nymphs, and adults had longer feeding periods on tortoises than on guinea pigs. Adult females fed on tortoises had greater engorgement wieght and ovipositional capacity than ticks fed on guinea pigs. It is suggested that the shortened feeding period of immature stages on mammalian hosts together with the occurrence of morphogenic diapause may be more important than previously recognized in determining whether the life cycle of A. marmoreum is completed in 1 or 2 yr under natural conditions. PMID- 1404253 TI - Immunization of rabbits against nymphs of Amblyomma hebraeum and A. marmoreum (Acari: Ixodidae). AB - Himalayan rabbits immunized with homogenates prepared from nymphs of Amblyomma hebraeum Koch and A. marmoreum Koch ticks developed humoral and probably also cell-mediated immunity to their respective homogenates. Beta and gamma globulin levels and numbers of eosinophils and neutrophils increased significantly in inoculated rabbits. The recipient animals developed resistance to homospecific nymphal infestations. Cross resistance between the two species was not evaluated. Nymphs of both species that fed on inoculated rabbits demonstrated slightly shorter feeding periods, and their mean weights were significantly lower than nymphs that fed on Quil 'A' adjuvant-inoculated rabbits or on naive rabbits. Significantly higher proportions of nymphs from immunized animals failed to moult when compared with nymphs that fed on the two control groups. These parameters indicate that the inoculated rabbits had acquired protective immunity against nymphs of both ticks. PMID- 1404254 TI - Parasitic arthropods of sympatric meadow voles and white-footed mice at Fort Detrick, Maryland. AB - Twelve species of parasitic arthropods (one sucking louse, two fleas, one tick, and eight mites) were recovered from 51 meadow voles, Microtus pennsylvanicus (Ord); whereas nine species (one sucking louse, one bot, three fleas, one tick, and three mites) were collected from 48 white-footed mice, Peromyscus leucopus (Rafinesque), live-trapped on the grounds of Fort Detrick, Frederick County, MD., during 1990 and 1991. The most commonly collected arthropods from M. pennsylvanicus were the fur mite, Listrophorus mexicanus Fain (approximately 2,720 specimens); the tropical rat mite, Ornithonyssus bacoti (Hirst) (987); the laelapid mites, Laelaps kochi Oudemans (733) and Androlaelaps fahrenholzi (Berlese (322); the sucking louse, Hoplopleura acanthopus (Burmeister) (121); the tick, Dermacentor variabilis (Say) (47); and the chigger mite, Neotrombicula whartoni (Ewing) (45). Arthropod densities were lower on P. leucopus, from which the most frequently recorded species were the sucking louse, Hoplopleura hesperomydis (Osborn) (98 specimens); the fleas, Epitedia wenmanni (Rothschild) (85) and Orchopeas leucopus (Baker) (61); and the mite, A. fahrenholzi (83). Although six species of arthropods parasitized both species of rodents, only two of these, A. fahrenholzi and D. variabilis, were relatively common on both hosts. Therefore, although the habitats of both host species partially overlap, their associated parasitic arthropods remain principally host specific. The potential significance of these findings with respect to vector-borne disease transmission is discussed. PMID- 1404255 TI - Replication and tissue tropisms of Crimean-Congo hemorrhagic fever virus in experimentally infected adult Hyalomma truncatum (Acari: Ixodidae). AB - Adult Hyalomma truncatum Koch ticks were inoculated intracoelomically with Crimean-Congo hemorrhagic fever (CCHF) virus to examine tissue tropisms of this virus in ticks. Virus was recovered from all 185 ticks examined between 2 and 42 d after inoculation with CCHF virus. Titers or virus recovered from unfed male and female ticks were essentially the same (means, 10(2.4) and 10(2.5) plaque forming units [PFU] per tick, respectively). Infection rates and titers recovered per gland for both salivary glands and reproductive tissues (ovaries and testes) were positively associated with blood feeding; average titers were 10-fold greater in organs from fed compared with those from unfed individuals. In contrast, neither the tick's sex nor feeding status (unfed or engorged) affected the titer of virus recovered from hemolymph (mean, 10(1.6) PFU/microliters). Although virus was recovered from Malpighian tubules, midgut, muscle, and nervous tissues from nearly all of the ticks tested, viral titers were consistently low. The increase in viral titer associated with blood feeding by ticks appeared to be due primarily to proliferation of tissue (e.g., salivary gland and reproductive tissues), rather than to increased replication in tissue already present. PMID- 1404257 TI - Differences in male mating response and female flight sounds in Aedes aegypti and Ae. albopictus (Diptera: Culicidae). AB - Aedes aegypti (L.) and Ae. albopictus (Skuse) showed similar rates and timing of insemination in the laboratory. Laboratory attempts at interspecific mating were unsuccessful. Because Ae. aegypti males are known to locate females by flight sounds, male response to sound was compared in the two species. Ae. aegypti males responded to female flight sounds with stereotypical orientation and mating behavior, whereas Ae. albopictus males seldom responded. Recorded flight sounds of females were sampled via computer digitization and compared. Ae. aegypti females produced louder sounds with more harmonics than Ae. albopictus. Males were tested for their ability to discriminate between the sounds of the two species. Ae. albopictus males did not respond to recordings of either Ae. albopictus or Ae. aegypti females. Ae. aegypti males responded preferentially to the recorded sounds of Ae. aegypti females. Thus, males of the two species use different mechanisms in locating mates. Ae. aegypti males rely more on sound than do Ae. albopictus males. PMID- 1404256 TI - Immune response of lizards and rodents to larval Ixodes scapularis (Acari: Ixodidae). AB - The house mouse (laboratory strain), Mus musculus (L.), the cotton mouse, Peromyscus gossypinus (LeConte), the broad-headed skink, Eumeces laticeps (Schneider), and the guinea pig, Cavia porcellus (L.), were successively infested five times with larvae of the blacklegged tick, Ixodes scapularis Say. Tick feeding success, engorgement weight, and subsequent molting success were measured after each infestation. A greater percentage of ticks (P less than 0.05) fed on M. musculus and E. laticeps than on P. gossypinus or C. porcellus. P. gossypinus expressed a transitory partial resistance, measured in percentage of ticks feeding, during the third infestation but showed increased tolerance during the fourth and fifth infestations. Ticks fed on E. laticeps were heavier than those fed on any other host (P less than 0.05). Those fed on M. musculus were heavier than those fed on P. gossypinus, but the difference was not statistically significant. On C. porcellus, only 1.6% of larvae from the third infestation and none thereafter engorged; weights of larvae from first and second infestations were higher (P less than 0.05) than those fed on M. musculus and P. gossypinus and lower (P less than 0.05) than those fed on E. laticeps. A greater percentage of larvae from E. latticeps and M. musculus (P less than 0.05) molted to nymphs compared with those from P. gossypinus and C. porcellus. Molting success was the same for ticks fed on P. gossypinus and on C. porcellus during the first and second infestations. M. musculus, P. gossypinus, and E. laticeps expressed no resistance (measured as percentage feeding, engorgement weight, and molting) to feeding by I. scapularis larvae after five infestations. Host serum was tested using an ELISA for detection of antibodies against I. scapularis salivary gland antigens before and after each infestation. Antibodies were detected after the second infestation and thereafter in C. porcellus, the only species to show antibodies or to express and maintain an acquired resistance to tick feeding throughout five infestations. PMID- 1404258 TI - Experimental transmission of Venezuelan equine encephalomyelitis virus by a strain of Aedes albopictus (Diptera: Culicidae) from New Orleans, Louisiana. AB - Experimental studies were undertaken to ascertain the vector competence of a strain of Aedes albopictus (Skuse) collected in New Orleans, LA, (Gentilly strain) for an epizootic (Trinidad donkey) strain of Venezuelan equine encephalomyelitis (VEE) virus. This strain of Ae. albopictus was significantly more susceptible to infection with VEE virus than were any of the four strains tested previously, including two from North America and two from South America. Likewise, dissemination (148 of 180) (82%) and transmission (40 of 88) (45%) rates were significantly higher in the Gentilly strain than in any of the strains previously tested. Analysis of the results of the present study along with those of a previous study with a second alphavirus, chikungunya (CHIK) virus, indicated that, although all three strains of Ae. albopictus tested were more susceptible to VEE virus than to CHIK virus, susceptibility to infection and dissemination with one alphavirus appeared to be directly related to susceptibility to infection and dissemination with the other virus and may indicate shared receptor sites for these two alphaviruses in Ae. albopictus. PMID- 1404259 TI - Attempted mechanical transfer of Ehrlichia risticii by tabanids (Diptera: Tabanidae). AB - The ability of tabanid mouthparts to retain and to transfer mechanically Ehrlichia risticii Holland, Weiss, Burgdorfer, Cole & Kakoma was evaluated by feeding flies on infected and noninfected mice and on capillary tubes containing infected cells and cell-free medium. Flies representing two genera and 29 species were collected at equine boarding stables, farms, and along riding trails in Wake, Johnston, and Duplin counties in North Carolina for the feeding trials. Two species, Tabanus fulvulus Wiedemann and T. pallidescens Philip, fed on mice but failed to transfer the pathogen from infected to susceptible mice. Chrysops vittatus Wiedemann, Tabanus americanus Forster, and T. sulcifrons Macquart transferred E. risticii-infected cells from capillary tubes containing infected cells in medium to tubes containing medium. These studies document that E. risticii-infected cells can be retained on mouthparts and potentially transferred by tabanids. PMID- 1404260 TI - Incompetence of roe deer as reservoirs of the Lyme borreliosis spirochete. AB - To determine whether the roe deer, Capreolus capreolus L. may serve as a reservoir host for the Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, evidence of spirochetal infection was sought in nymphal Ixodes ricinus (L.) that had engorged as larvae on roe deer. Sixteen roe deer were shot in Lyme disease enzootic areas of south-central Sweden during August-November 1990 and August 1991. An average of 276 (range, 84-658) larvae of I. ricinus was collected from each of 12 deer shot in August. Of those ticks that had fed on deer and then developed to the nymphal stage, the gut contents of 238 were examined by phase-contrast microscopy. All these ticks were negative for spirochetes, whereas 4.2% contained Trypanosoma cf. cervi Kingston & Morton and 15.1% contained the nematode Dipetalonema rugosicauda Meszaros & Sugar. A total of 396 nymphal ticks was collected by blanket-dragging during May-June 1991 and examined for spirochetes; 9.1% of these host-seeking nymphs were infected with spirochetes. Although the roe deer serves as a principal blood source for all stages of I. ricinus, it does not appear to serve as a major reservoir of B. burgdorferi. PMID- 1404261 TI - Modulation of host-immune responses by ticks (Acari: Ixodidae): effect of salivary gland extracts on host macrophages and lymphocyte cytokine production. AB - Ixodid tick infestation induces host acquired resistance, which involves immunoglobulin cell-mediated and complement-dependent effector pathways. Ticks have developed countermeasures to modulate host antiarthropod responses. Ixodid mediated host immunomodulation results in vitro in reduced responsiveness to T lymphocyte mitogens for cells obtained from infested hosts and impaired antibody responses to a thymic dependent antigen. Salivary gland extracts from days 0-9 of engorgement from unmated, female Dermacentor andersoni Stiles suppressed lymphocyte proliferative responses (LPS) to the T-cell mitogen Con A up to 68.4%, whereas responsiveness to E. coli LPS was enhanced. Cytokines assessed in this study included interleukin-1, IL-1, and tumor necrosis factor (TNF) alpha produced by macrophages, and interleukin-2, IL-2, and gamma interferon (IFN-G) secreted by T-lymphocytes. Salivary gland extracts prepared from tissues obtained on days 0-5 of engorgement suppressed IL-1 elaboration from 89.8% on day 0 through 37.5% on day 6. Levels of TNF were reduced from 40.7 to 94.6% throughout the course of the study. Production of IL-2 was suppressed by 14.1-31.9%, and IFN G was reduced by 8.7-57.0%. Reduced IL-1 levels during the early phases of feeding indicated reduced host ability to activate T-lymphocytes and provide costimulatory, differentiation, and development signals for B-cells. Both IL-1 and TNF are endogenous pyrogens and activate polymorphonuclear leukocytes. Activities of TNF and IFN-G include antiviral properties and induction of expression of class I and II major histocompatibility complex molecules, which are critical components in the recognition of antigen by T-lymphocytes. The autocrine role of IL-2 in proliferation of T-lymphocytes is central to the development of immune reactivity involving T-cell regulation or effector functions or both. Reductions in cytokine levels would suppress immune responses directed toward immunogens introduced into the host during the course of tick feeding. These results indicates that immunomodulation of the host during tick feeding facilitates engorgement and pathogen transmission. PMID- 1404262 TI - Comparative infections of epizootic and enzootic strains of Venezuelan equine encephalomyelitis virus in Amblyomma cajennense (Acari: Ixodidae). AB - To compare the potential for an enzootic or an epizootic strain of Venezuelan equine encephalomyelitis (VEE) virus to infect Amblyomma cajennense (F.), larval ticks were fed on guinea pigs (strain 13) inoculated with an enzootic viral strain of variant I-E (68U201) or on guinea pigs inoculated with an epizootic strain of variant I-A (Trinidad donkey). Peak viremias were 10(5.2) plaque forming units (PFU)/ml and 10(7.3) PFU/ml in guinea pigs infected with enzootic and epizootic viral strains, respectively. Ticks feeding on enzootic- and epizootic-infected hosts had viral titers of 10(2.5) and 10(3.9) PFU per tick, respectively, at drop-off. Although epizootic virus was recovered from 98% (127 of 130) of larval ticks up to 16 d after drop-off, enzootic virus was recovered from 95% (19 of 20) at drop-off (mean titer, 10(2.5) PFU per tick), with recovery rates declining rapidly to 2 of 10 (mean titer, 10(1.4) PFU per tick) by 16 d after drop-off. Transstadially transmitted epizootic virus was found in 0.4% (12 of 2,950) of unfed nymphs (mean titer, 10(2.8) PFU per tick) 63 d after drop-off, 1% (5 of 521) fed nymphs 69 d after drop-off, and 1% (4 of 400) of unfed adults (mean titer, 10(3.6) PFU per tick) 106 d after drop-off. No enzootic virus was recovered from 4,600 unfed nymphs tested 63 d after drop-off. PMID- 1404264 TI - Patterns of sugar feeding in diapausing and nondiapausing Culex pipiens (Diptera: Culicidae) females. AB - In the laboratory, diapausing Culex pipiens L. females fed on a continuously available sugar source more frequently and longer after adult emergence than did non-diapausing females. They also showed an extended nocturnal pattern of sugar feeding compared with that of non-diapausing females. Differences between diapausing and non-diapausing females with respect to sugar feeding and host seeking behavior also were related to responses to volatiles from fruit and vertebrate hosts. In this Colorado strain of Cx. pipiens, increased sugar feeding by diapausing females during the first few weeks of adult life may be an adaptation that enhances overwintering survival. PMID- 1404263 TI - Cotton rats and other small mammals as hosts for immature Dermacentor variabilis (Acari: Ixodidae) in central Oklahoma. AB - Eight species of small mammals were evaluated as potential hosts for American dog ticks, Dermacentor variabilis (Say), in an upland, tallgrass prairie study site in central Oklahoma. Only hispid cotton rats, Sigmodon hispidus, and deer mice, Peromyscus maniculatus, were found to be important hosts for immature D. variabilis. Although D. varibilis larvae and nymphs frequently infested both cotton rats and deer mice, cotton rats were the most important host species for both immature stages in the study area. Cotton rats constituted 63.2% of the total 530 small mammals captured and were hosts to 85.2% of all larvae and 88.7% of all nymphs. Deer mice accounted for 19.8% of all small mammals captured and were hosts for 14.5% of the larvae and 10.8% of the nymphs recovered. The remaining small mammal species were hosts for less than 1% of the immature ticks collected. Larval infestations peaked during summer, whereas summer and spring peaks were noted for the nymphal infestations. The relative importance of cotton rats and deer mice as hosts for immature ticks could be largely, but not completely, explained by cotton rats being more than three times as abundant as deer mice. Attachment site data indicated that differences in grooming behavior also might be partially responsible for the larger infestations observed on cotton rats. Other possible ecological and behavioral explanations of the heavy infestations observed on cotton rats are discussed. PMID- 1404265 TI - Transmission of western equine encephalomyelitis virus by Argentine Aedes albifasciatus (Diptera: Culicidae). AB - Aedes albifasciatus (Macquart) has been considered a potential vector of western equine encephalitis (WEE) virus in Argentina because it has been found naturally infected, it is susceptible to infection per os, and its distribution and feeding habits are compatible with those of an epizootic and epidemic vector. Ae. albifasciatus females collected in the vicinity of Cordoba, Argentina, were highly susceptible to WEE virus perorally (ID50 less than 0.5 Vero cell plaque forming units) when fed on viremic chicks. Virus transmission trials were done 9 to 16 d after infection by feeding potentially infected mosquitoes individually on chicks. Among 31 mosquitoes that survived the incubation period, six refed on susceptible chicks. Virus transmission by bite was demonstrated by five of six (83%) mosquitoes. Therefore, the final piece of evidence incriminating Ae. albifasciatus as a natural vector of WEE virus has been obtained. This is the first mosquito species to be incriminated as a vector of WEE virus in South America. PMID- 1404266 TI - Development and evaluation of an enzyme-linked immunosorbent assay for Plasmodium vivax-VK247 sporozoites. AB - An enzyme-linked immunosorbent assay (ELISA) for the Plasmodium vivax-VK247 (variant) circumsporozoite (CS) protein was developed and evaluated using sporozoites produced by feeding mosquitoes on Thai patients with parasitologically confirmed P. vivax infections. The ELISA had a detection threshold of fewer than 50 sporozoites. Using this assay in conjunction with an ELISA for the VK210 polymorph, nearly 16% of the 235 P. vivax cases produced sporozoites positive only for the variant; 69% produced sporozoites positive only in the VK210 assay; and 15% were positive in both assays, indicating mixed infections. Twelve cases (5%) produced sporozoites negative in one assay and with unexpectedly low activity in the other ELISA, indicating the possibility of other CS protein polymorphs. PMID- 1404267 TI - Bite-count evaluation of the repellency of N,N-diethyl-3-methylbenzamide to larval Eutrombicula alfreddugesi (Acari: Trombiculidae). AB - Larvae of the pest chigger mite Eutrombicula alfreddugesi Oudemans, 1910, exhibited a low repellent threshold for N,N-diethyl-3-methylbenzamide (deet) in a field setting. Use of a deet-based repellent significantly reduced chigger mite infestation. Efficacy of aerosol formulations was significantly diminished with 9% (AI) deet. E. alfreddugesi utilized both direct and indirect paths to infest the human body. Direct infestation led to the highest body region bite counts. Distribution of E. alfreddugesi bites over 15 regions of the human body fell into three zones of decreasing parasitism: the ankle/calf region (accessed through direct infestation); the groin, chest, back, armpits, and feet (accessed through indirect infestation); and the thighs, arms, buttocks, head, and neck, which were infrequently attacked or were unavailable to E. alfreddugesi. PMID- 1404268 TI - Kinetic development and decline of antiscrewworm (Diptera: Calliphoridae) antibodies in serum of infested sheep. AB - Sheep infested with screwworms, Cochliomyia hominivorax (Coquerel), produced specific serum antibodies detectable by ELISA. Significant antibody levels were found beginning at 1 wk after infestation and persisting for 2 mo, with peak levels at 3 wk after infestation. Mean response values and corresponding larval survivorship were similar over a range of 25 to 200 larvae per individual sheep. Anomalous seropositive responses in some noninfested sheep suggested the possibility of cross-reactivity between antigens of screwworm and those of related myiasigenic blowflies. PMID- 1404269 TI - African swine fever virus infection in the Iberian soft tick, Ornithodoros (Pavlovskyella) marocanus (Acari: Argasidae). AB - One thousand six hundred Ornithodoros (Pavlovskyella) marocanus Velu larvae were fed on a pig infected with African swine fever virus (titer: 10(7.4) HAd50/ml), and 1,600 larvae were fed on an uninfected pig. Ticks in each group were compared for mortality rates, mean time to death for ticks that died, mean time from feeding to either molting or eclosion, percentage of ticks that eclosed or molted, and the number of blood meals per nymph or instar. Cumulative virus induced mortality for all immature stages (larvae to adult) of O. marocanus that had been fed as larvae on a pig infected with African swine fever was ca. 73% over a 390-d period. In contrast, less than 9% mortality was observed among ticks fed on uninfected pigs. Mean time to death for infected ticks was 15-87 d versus 10-17 d for uninfected ticks. Differences in the premolt period (number of days from blood meal to molt) between infected and control ticks were not observed. Mean premolt periods for larvae and first-, second-, third-, fourth-, and fifth instar nymphs fed on pigs were 7, 9, 15, 11, 15, and 15 d, respectively. The majority of infected and all uninfected ticks required only one blood meal from pigs to molt. Mean weights for unfed second-, third-, and fourth-instar nymphs and males and females were 0.50, 0.67, 3.07, 3.63, and 5.91 mg, respectively. PMID- 1404270 TI - Nectar sources and age structure in a population of Aedes provocans (Diptera: Culicidae). AB - Gonotrophic-age structure of a population of Aedes provocans (Walker) and nectar sources used by adults were studied for 2 yr at a field site near Belleville, Ontario, Canada. Females emerged during a short period, and aging of the population was highly synchronous. Complete parity of the population was achieved within about 17 d in 1978 and 27 d in 1979. Some females completed as many as four gonotrophic cycles. This synchronous pattern of population aging is compared with patterns in other species of snow-melt Aedes, which typically age much more gradually. The pattern of synchronous aging permitted estimation of daily mortality rates from an index of population size derived from human-bait catches; peaks in the biting index were related to each gonotrophic cycle in the population. Nectar sources for adults were ranked according to abundance and the extent to which they were used by Ae. provocans, permitting a coarse, semiquantitative estimate of preferences. Ae. provocans obtained nectar from the extrafloral nectaries of one species and the floral nectaries of 19 species of angiosperms. Shrubs and trees, especially of the Rosaceae (primarily species of Prunus), were particularly important as nectar sources and bloomed concurrently with the appearance of nulliparous females. Sharp declines in the population of Ae. provocans were associated with the cessation of blooming of these plant species. It is hypothesized that the highly synchronous pattern of gonotrophic aging in Ae. provocans was attributable, in part, to the ready availability of nectar sources and bloodmeal hosts near breeding sites. PMID- 1404271 TI - Scanning electron microscopy of egg hatching of Anopheles albimanus (Diptera: Culicidae). AB - Scanning electron and light microscopic observations showed that egg hatching in Anopheles albimanus Wiedemann is aided by a chisel-shaped spine. This hatching tooth is surrounded by a thin flexible membrane fixed to a groove in the head of the larvae. Increased intracranial pressure may force the spine against the egg shell until a fissure is produced. Further opening of the egg is achieved by movements of the head and the entire body of the larva. PMID- 1404272 TI - Leishmania infantum MON-98 isolated from naturally infected Phlebotomus langeroni (Diptera: Psychodidae) in El Agamy, Egypt. AB - Leishmania infantum zymodeme MON-98 was isolated in El Agamy, Egypt. A total of 15 (1.07%) Leishmania-like infections in the anterior midgut and in the head was found in 1,405 Phlebotomus langeroni (Nitzulescu); none of 1,785 Phlebotomus papatasi (Scopoli) was found infected. Four of the 15 cultures (26.7%) were indistinguishable from a reference L. infantum MON-98 strain using cellulose acetate electrophoresis. The isolation and identification of L. infantum MON-98 from naturally infected P. langeroni confirms that this species of sand fly is the vector of visceral leishmaniasis in El Agamy. PMID- 1404273 TI - Tests for the existence of genetic determination or conditioning in host selection by Anopheles albimanus (Diptera: Culicidae). AB - The existence of sympatric populations within Anopheles albimanus Wiedemann with specific host preferences and the question of whether host selection has a genetic basis or is a learned characteristic were investigated. Progeny of wild females collected from corrals or human bait were reared in an insectary. F1 females were fed on a cow or on a human host, allowed to oviposit, and then were released in an experimental hut divided into three compartments. The side rooms occupied by two human or one calf baits were connected by a "funnel-like" cone with the central room in which mosquitoes were released. Females were released at 2000 hours and recaptured the next morning at 0600 hours. A fixed proportion of mosquitoes selected either host (approximately 65% cow and 35% human), irrespective of their parental origin or source of the first blood meal. The data indicate that the existence of cryptic populations with anthropophilic habits is unlikely and that a "learned" host selection also may be ruled out. PMID- 1404274 TI - Use of an aquatic light trap for monitoring larval population of Culex quinquefasciatus (Diptera: Culicidae). AB - An aquatic light trap was evaluated in wading pools placed in a greenhouse as a method of sampling populations of mosquito larvae. Three replicated experiments examined the effect of the color of a Cyalume light source and the vertical placement of the trap within the water column. Traps placed with the entrance funnel opening at the surface of the water collected significantly more fourth instar Culex quinquefasciatus than did those with the entrance submerged. When traps were placed near the surface of the water, those with blue, yellow, and white light sticks, as well as unlighted control traps, collected approximately the same number of larvae. Therefore, a small change in trap position was more important than the presence of a light source in the effectiveness of this aquatic light trap as a sampling device for mosquito larvae. PMID- 1404275 TI - Evaluation of devices for removing attached Rhipicephalus sanguineus (Acari: Ixodidae). AB - Three types of forceps and a commercially available device, the Tick Solution, were used to remove adult brown dog ticks, Rhipicephalus sanguineus (Latreille), from dogs. The Tick Solution proved least effective at removing ticks, requiring significantly more removal attempts compared with forcep-removal methods. Medium tipped angled forceps provided the best overall performance. Other advantages and disadvantages of the devices are discussed. PMID- 1404276 TI - Resuscitation policies--action required. PMID- 1404277 TI - In the genes or in the stars? Children's competence to consent. AB - Children's competence to refuse or consent to medical treatment or surgery tends to be discussed in terms of the child's ability or maturity. This paper argues that the social context also powerfully influences the child's capacity to consent. Inner attributes and external influences are discussed using an analogy of the genes and the stars. PMID- 1404279 TI - 'Aid-in-dying' and the taking of human life. AB - In several US states, the legalisation of euthanasia has become a question for voters to decide in public referenda. This democratic approach in politics is consistent with notions of personal autonomy in medicine, but the right of choice does not mean all choices are morally equal. A presumption against the taking of human life is embedded in the formative moral traditions of society; human life does not have absolute value, but we do and should impose a strict burden of justification for exceptions to the presumption, as exemplified by the moral criteria invoked to justify self-defence, capital punishment, or just war. These criteria can illuminate whether another exception should be carved out for doctor assisted suicide or active euthanasia. It does not seem, in the United States at any rate, that all possible alternatives to affirm the control and dignity of the dying patient and to relieve pain and suffering, short of taking life, have been exhausted. Moreover, the procedural safeguards built into many proposals for legalised euthanasia would likely be undone by the sorry state of the US health care system, with its lack of universal access to care, chronic cost-containment ills, a litigious climate, and socioeconomic barriers to care. There remains, however, common ground in the quest for humane care of the dying. PMID- 1404278 TI - Baby marrow: ethicists and privacy. AB - A family had a child in large part to use its marrow in the hopes of saving the life of an older child afflicted with leukaemia. Public response from medical ethicists was negative. This paper argues that what the family did was not clearly wrong and that the ethicists should not have made public pronouncements calling the morals of the family into question. PMID- 1404280 TI - Legislation on euthanasia: recent developments in The Netherlands. AB - Recently, new developments took place in the Dutch debate on the legislation of euthanasia. After a brief account of that debate, the article discusses a new government proposal for legislation in this field, which was submitted to the Dutch parliament in November 1991. This proposal relates not only to euthanasia but also to some other medical decisions concerning the end of life. The author concludes that, for several reasons, it is unsatisfactory. PMID- 1404281 TI - Measuring the ethical sensitivity of medical students: a study at the University of Toronto. AB - An instrument to assess 'ethical sensitivity' has been developed. The instrument presents four clinical vignettes and the respondent is asked to list the ethical issues related to each vignette. The responses are classified, post hoc, into the domains of autonomy, beneficence and justice. This instrument was used in 1990 to assess the ethical sensitivity of students in all four medical classes at the University of Toronto. Ethical sensitivity, as measured by this instrument, is not related to age or grade-point average. Sensitivity increases between the 1st and 2nd year and then decreases throughout the rest of undergraduate medical training, such that the 4th-year students identify fewer issues than those entering medical school. Students expressing a career choice of family medicine identify more issues than their peers. Several problems with the use of the instrument and the interpretation of the data were found. Nonetheless, these findings, if reproducible, are important and their meaning needs further discussion. PMID- 1404282 TI - Learning to see: moral growth during medical training. AB - During medical training students and residents reconstruct their view of the world. Patients become bodies; both the faults and the virtues of the medical profession become exaggerated. This reconstruction has moral relevance: it is in part a moral blindness. The pain of medical training, together with its narrowness, contributes substantially to these faulty reconstructions. Possible improvements include teaching more social science, selecting chief residents and faculty for their attitudes, helping students acquire communication skills, and helping them deal with their own pain. Most importantly, clearer moral vision requires time and scope for reflection. PMID- 1404283 TI - When loyalties are divided between teachers and patients. AB - Three situations are described where a junior doctor is required by his consultant to do something that he thinks is not in the patient's best interests. The dilemma is explored from the perspective of patients' interests being the doctor's first concern; of the importance of respect for medical teachers, and of the implications of an apprenticeship model of postgraduate medical training. PMID- 1404284 TI - Stress. AB - 'Stress' is a widely used word in clinical practice, the biological sciences and everyday life; but one which has little real value, serving mainly to confuse and confound rational thought. Whether it is described in terms of stimulus, response, or a combination of the two the definitions of stress are invariably found to be circular. We should stop using the word 'stress' and instead discuss specific stimuli or responses as appropriate. The author suggests that 'pressure' and 'tension' might provide suitable substitutes for everyday clinical practice. PMID- 1404286 TI - Open letter. PMID- 1404285 TI - Ethical questions about peer review. PMID- 1404287 TI - Alternative medicine: response to Kottow. PMID- 1404288 TI - 'Unprincipled QALYs'. PMID- 1404289 TI - National haemophilia B molecular genetic register. PMID- 1404290 TI - A new strategy for the genetic counselling of diseases of marked mutational heterogeneity: haemophilia B as a model. PMID- 1404291 TI - X inactivation as a mechanism of selection against lethal alleles: further investigation of incontinentia pigmenti and X linked lymphoproliferative disease. AB - Thirty-one females with incontinentia pigmenti (IP), 42 controls, and 11 females from four families segregating for X linked lymphoproliferative disease (XLP) were studied for evidence of skewed X inactivation by analysis of methylation at sites in the HPRT, PGK, and M27 beta (DXS255) regions of the X chromosome. Extensive skewing of X inactivation was present in blood from 4/42 (9.5%) control females and 11/31 (35%) of those with IP. This frequency of skewed inactivation was seen in both familial and sporadic cases of IP. Analysis of inactivation in mother/daughter pairs, both affected and control subjects, showed no familial consistency of pattern, arguing against specific mutations being associated with particular patterns of inactivation. In the only informative family where both mother and daughter were affected by IP and showed skewed inactivation, the IP mutation was on the active X chromosome. This argues against cell selection during early embryogenesis being the explanation for the skewed inactivation observed. These data confirm that skewed inactivation of one X is observed in lymphocytes from a significant minority of normal females, and is seen with raised frequency in IP heterozygotes. It is not, however, a universally observed phenomenon, and the relationship of X inactivity to the IP mutation appears to be complex. In the case of XLP, though skewed X inactivation patterns are seen in most disease carriers, the frequency with which this phenomenon occurs in normal females renders it an unreliable diagnostic marker for XLP carriers. PMID- 1404292 TI - Chromosomal localisation of a pseudoautosomal growth gene(s). AB - Although recent molecular studies in patients with sex chromosome aberrations are consistent with a growth gene(s) being present in the pseudoautosomal region (PAR), the precise location has not been determined. In this report, we describe a Japanese boy and his mother with an interstitial deletion in Xp22.3 and review the correlation between genotype and stature in six cases of partial monosomy of the PAR. The results indicate that the region from DXYS20 to DXYS15 is the critical region for the putative growth gene(s). PMID- 1404293 TI - The acrocallosal syndrome and Greig syndrome are not allelic disorders. AB - Acrocallosal syndrome is an autosomal recessive form of polysyndactyly associated with mental retardation and agenesis of the corpus callosum. There have been suggestions that it is allelic to the Greig cephalopolysyndactyly syndrome. Linkage analysis, using flanking markers, shows this suggestion is unlikely to be correct. PMID- 1404294 TI - Multipoint mapping of adult onset polycystic kidney disease (PKD1) on chromosome 16. AB - Analysis of genetic linkage data in 33 adult onset polycystic kidney (ADPKD) families was carried out using probes for the D16S85, D16S84, and D16S94 loci. The data set of 33 families shows no evidence of genetic heterogeneity since one unlinked family was previously excluded. Two point linkage analysis showed maximum likelihood values of the recombination fraction of 0.07 for ADPKD and D16S85 (lod score 18.78), 0.02 for ADPKD and D16S84 (lod score 7.55), and 0.00 for ADPKD and D16S94 (lod score 6.73). Multipoint analysis showed a maximum likelihood order of tel-D16S85-0.06-D16S84-0.02-(PKD1, D16S94)-cen with a multipoint lod score of 32.16. Analysis of rare recombinants lying close to PKD1 gave results consistent with this order. PMID- 1404295 TI - Cartilage-hair hypoplasia in Finland: epidemiological and genetic aspects of 107 patients. AB - Cartilage-hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia characterised by short limbed short stature, hypoplastic hair growth, and impaired cell mediated immunity and erythrocyte production. The syndrome is exceptionally prevalent among the Finns and among the Old Order Amish in the United States; sporadic cases have been reported from other countries. An epidemiological and genetic study of CHH in Finland showed 107 patients, 46 males and 61 females, in 85 families. Eighteen of them had died, seven before the age of 1 year. The living patients ranged in age from 1 to 51 years, median 21 years. The incidence was estimated to be 1:23,000 live births. Consanguinity was found in two families and interfamilial relationships in 20 families. Geographical distribution of the birth places of the patients and their great grandparents showed accumulation in a small area in western Finland and regional clusters were seen in other parts of the country as well. The result of the segregation analysis was in accordance with recessive inheritance with reduced penetrance. PMID- 1404296 TI - Screening for phenylketonuria in a totalitarian state. AB - Living under a totalitarian regime has many effects on the structure, way of thinking, and relations in a society. However, it is the impact on neonatal genetic screening that we discuss in this paper. Genetic screening functions at the interface between health services and society at large. Being involved for over a decade in setting up the Bulgarian PKU screening programme, we have had to deal with ways and attitudes which may be difficult for the western mind to grasp. Yet comprehension is very much needed in the new world we are trying to create. PMID- 1404297 TI - Weyers' ulnar ray/oligodactyly syndrome and the association of midline malformations with ulnar ray defects. AB - We describe a two generation family with variable ulnar and radial ray reduction and midline craniofacial abnormalities. The features suggest a diagnosis of Weyers' ulnar ray/oligodactyly syndrome originally described in two isolated cases. Syndromes of ulnar ray reduction are briefly reviewed and the relationship between limb bud and midline development discussed. PMID- 1404298 TI - X inactivation patterns in females with Alport's syndrome: a means of selecting against a deleterious gene? AB - The patterns of X chromosome inactivation in 43 females from families segregating classic Alport's syndrome (AS) (X linked hereditary nephritis with deafness) have been analysed. AS carrier females have a most variable clinical course. The aim of the study was to establish whether there was any correlation between the X inactivation pattern of a carrier female and the severity of her disease. No correlation was found in DNA derived from peripheral blood lymphocytes. However, it remains possible that differential patterns of X inactivation may occur in the tissues affected by AS, namely the basement membrane of the kidney, eye, and ear. PMID- 1404299 TI - Autosomal dominant retinitis pigmentosa (ADRP): a rhodopsin mutation in a Scottish family. PMID- 1404300 TI - New dysmorphic features in Rubinstein-Taybi syndrome. AB - We report a new case of Rubinstein-Taybi syndrome with a hypoplastic right kidney, persistent pulmonary hypertension, and mitral valve regurgitation. Other pertinent features included broad thumbs, broad big toes, syndactyly of the third and fourth fingers bilaterally, beaked nose, broad columella of the nose, patent ductus arteriosus, and motor and mental retardation. The testes were descended. The 3 month old patient had delayed motor and mental development corresponding to a 1 month old infant. PMID- 1404301 TI - 18p- syndrome and hypopituitarism. AB - A patient is described with 18p- syndrome and hypopituitarism. This is the first patient with this syndrome who has been shown to benefit from growth hormone therapy. Patients with this syndrome who have growth deficiency should be considered for evaluation for hypopituitarism, if the quality of their lives would improve with an increase in stature. PMID- 1404302 TI - Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: a new syndrome? AB - A male infant was found to have bilateral exudative retinopathy at 6 months of age. A month later severe aplastic anaemia was diagnosed, eventually leading to the infant's death. Additional features of this seemingly new syndrome were intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia because of cerebellar hypoplasia, cerebral calcifications, extensor hypertonia, and progressive psychomotor retardation. PMID- 1404303 TI - Unknown syndrome: nasal hypoplasia, sparse hair, truncal obesity, genital hypoplasia, and severe mental retardation. AB - A 4 year old girl is described with severe mental retardation, peculiar face with nasal hypoplasia, sparse hair, genital hypoplasia, truncal obesity, puffy hands, and small feet with complete cutaneous syndactyly of the second and third toes. PMID- 1404304 TI - A mutation in exon 7 of the CFTR gene is common in the western part of France. PMID- 1404305 TI - Beckwith-Wiedemann syndrome. PMID- 1404306 TI - Williams syndrome and chromosome 18. PMID- 1404307 TI - Design characteristics for drug nebulizers. AB - Drug nebulizers should be designed to produce an aerosol which efficiently targets drug to the respiratory tract. In this article we review the basic principles of aerosol generation from both jet and ultrasonic nebulizers, and the factors governing respiratory tract penetration and deposition. We review methods for accurate measurement of aerosol dose and size, with emphasis on evaporative effects and the implications to drug nebulizer design. We identify three forms of drug aerosol waste attributable to: generation of non-respirable aerosol, losses to the environment, and dead volume solution; and we consider how each may be minimized through good nebulizer design. Finally, we compare the relative merits of jet and ultrasonic nebulizers, and conclude by predicting a new trend in future drug nebulizer therapy. PMID- 1404308 TI - Interference problems and screening in NMR and MRI. AB - A pragmatic approach to interference in NMR and MRI systems is presented with the objective of raising the awareness of problems associated with larger installations. The basic premise is that an installation is a system composed of interconnected sub-systems, each with its own idiosyncracies. Consequently all problems should be considered from this view-point. Practical warnings and solutions are given along with simple mathematical equations to permit one to calculate some interference effects. Most problems are associated with RF and gradient sub-systems, so the main content deals with degradation of the NMR signal by noise and coherent RF interference and with the interaction of sub systems. Attention is drawn to the correct identification of the source of a problem, and the importance of a well engineered solution. 'Quick-fix repairs' can lead to very baffling problems when the system is reconfigured for a different experiment. PMID- 1404309 TI - Biparietal diameter: an alternative measure of head growth in the low-birthweight infant. AB - Reliability and validity of biparietal diameter (BPD) compared with head circumference (HC) measurement as an index of cranial growth was assessed. A significant correlation between BPD and HC (r = 0.857; p less than 0.0001) and an interobserver reliability of 92% were found. Infants' age and sex had independent effects on BPD growth rate. Very sick infants had a lower increase in BPD rate than healthy controls. It is suggested that in sick premature infants, when the head is encumbered by various types of apparatus, this technique might prove more feasible than HC measurement. PMID- 1404310 TI - Portable maximum respiratory pressure measurement--a comparison with laboratory techniques. AB - We have evaluated a new, hand-held, electronic device to measure maximal respiratory pressures, and compared its performance in normal subjects against two pre-existing methods. This new device produces accurate, reproducible results and has the advantages of easy use and portability, which allow it to be used at the patient's bedside, outpatient clinic or pulmonary function laboratory. PMID- 1404311 TI - Medical device regulations in the New Europe. AB - We are now in 1992, the year of the 'Completion of the Internal Market'. Big changes in the ways in which medical devices will be controlled in Europe are on the way, but many healthcare professionals are unaware of these changes and what they will mean to them. This article explains the moves that are now under way to harmonize medical device legislation throughout Europe and the many features, new to the UK, that they will introduce. PMID- 1404312 TI - Effects of skin blood flow and temperature on skin--electrode impedance and offset potential: measurements at low alternating current density. AB - Skin--electrode impedance was determined at 100 Hz and 1 kHz between two disposable electrodes, 5 cm apart, at current densities < 65 microA.cm-2. Measurements were made on the volar skin of the forearm during cooling on cardiopulmonary bypass, and on the dorsum of the foot in the absence of skin blood flow during aortic aneurysm repair. Both the resistive and reactive components of the skin-electrode impedence showed an inverse linear relationship to temperature between 26 and 36 degrees C. The magnitude of the impedance change was different for each patient studied; resistance changes ranged from 0.03 to 23.2 k omega. Degrees C-1 at 100 Hz and from 0.03 to 2.7 k omega. Degrees C-1 at 1 kHz, while reactance changes ranged from 0.4 to 2.1 k omega. Degrees C-1 at 100 Hz and from 0.04 to 0.18 k omega. Degrees C-1 at 1 kHz. Changes in skin-electrode impedance were not due to changes in skin blood flow. There was no consistent change in offset potential with temperature. Although the skin-electrode impedance increases as temperature falls, it is concluded that temperature effects at the skin-electrode interface are not responsible for the observed failure of evoked electromyography during clinical monitoring of neuromuscular function. PMID- 1404313 TI - Assessment of an infra-red non-contact sensor for routine skin temperature monitoring: a preliminary study. AB - The accuracy and reproducibility of a new non-contact sensor for monitoring skin temperature was examined. Thirty measurements taken by the device were compared with those taken by a commonly used thermocouple contact sensor. The result was a very high correlation coefficient (r = 0.9999). This accuracy was achieved with the probe held at an angle of 90 degrees 1 cm from the skin. Changes in angle and distance were found to contribute to measurement error. Little difference was found between 39 pairs of measurements taken of the left and right sides of subjects. However, intra-subject variability was noted with respect to the dermotomal segmental fields. Inter-tester reliability analysis resulted in a correlation of r = 0.937 involving two independent testers and 26 pairs of measurements. These preliminary data will be used for power calculations to study further the device which we found to be simple to operate, portable, and practical for routine clinical use. This sensor may have applications in the diagnosis of nerve and vascular disorders and in prospective monitoring of skin conditions such as bony areas at risk of pressure ulcers. PMID- 1404314 TI - Design and evaluation of an instrument to measure microcirculatory blood flow and oxygen saturation simultaneously. AB - There are compelling clinical advantages in being able to monitor, simultaneously and continuously, blood oxygen saturation and tissue perfusion from the same volume of tissue. We describe the design of a new instrument capable of combining both functions. It uses a laser diode at 805 nm to give a blood flow index and oxygenation information at that wavelength, and a pulsed LED at 660 nm to complete the estimation of oxygen saturation. By using a compensating photodetector these readings can be made relatively insensitive to sampling site. After calibrating the instrument on forehead sites it reliably read the oxygen saturation of sites on the thigh with a bias of -0.2% and a precision of +/- 1.7% relative to an IL 282 CO-oximeter. PMID- 1404316 TI - HSE scientist wins 1992 Beilby Award. PMID- 1404315 TI - An evoked compound electromyogram simulator with external microprocessor control facility. AB - A circuit for an evoked electromyogram simulator is described, which produces a biphasic triangular waveform similar to the evoked compound action potential seen during clinical quantitative neuromuscular monitoring. The device can produce a fading train-of-four sequence, which can be controlled using a single externally derived voltage. The simulator is useful for bench-testing of closed loop muscle relaxant administration systems, and for teaching aspects of neuromuscular monitoring in anaesthesia. PMID- 1404317 TI - Azole drug resistance in Candida species. PMID- 1404318 TI - Extracellular proteins as a potential marker of active Staphylococcus aureus infection in bone. AB - The potential of extracellular protein antigens of Staphylococcus aureus as markers of infection of bone was investigated by immunoblotting. Serum from patients with S. aureus bone infection showed levels of IgG antibodies to a preparation of soluble extracellular proteins of 17-81 kDa which were significantly higher than those found in serum from normal controls. By contrast, immunoblots of various whole cell or cell wall-derived antigens gave complex patterns of response which were unsuitable for positive diagnosis of S. aureus bone infection. PMID- 1404319 TI - The production of fatty acid modifying enzyme (FAME) and lipase by various staphylococcal species. AB - Eighty-six strains encompassing 11 species of coagulase-negative staphylococci were examined for the production of fatty acid modifying enzyme (FAME) and lipase. Staphylococcus schleiferi and S. saprophyticus most closely resembled S. aureus in that 80% of the strains produced both enzymes. In contrast, no strains of S. lugdunensis and S. haemolyticus tested produced these enzymes. S. simulans was unusual in that eight of 10 strains produced FAME, but only one produced lipase. Among the other species the proportion of strains producing both enzymes ranged from 10 to 60%. Generally there was a strong correlation between FAME and lipase production. PMID- 1404320 TI - The esterification of fatty acids by Staphylococcus aureus fatty acid modifying enzyme (FAME) and its inhibition by glycerides. AB - Fifty-five randomly selected Staphylococcus aureus strains were examined for fatty acid modifying enzyme (FAME) production. Of these, 20.4% did not elaborate the enzyme. Amongst the remaining strains, the lowest level produced in culture was 0.1 unit/10(9) cocci and the maximum was 2.01 U/10(9) cocci; the median level was 0.4 U/10(9) cocci. In a series of straight-chain saturated fatty acids with 11-24 carbons, all could be esterified by FAME. However, those with 15-19 carbons were generally better substrates than the others. For a particular chain length, the unsaturated forms were better substrates than the saturated form. Triglycerides with unsaturated fatty acid side chains were potent inhibitors of FAME. Diglycerides were almost as active as triglycerides, but monoglycerides were much less inhibitory. FAME was purified by gel filtration followed by hydrophobic interaction chromatography on hexyl agarose. FAME and lipase may have a role in determining the survival of S. aureus in lesions. PMID- 1404321 TI - The production of a bactericidal monoglyceride in staphylococcal abscesses. AB - The treatment of abscess homogenates with calcium ionophores stimulated the production of a bactericidal lipid with properties indistinguishable from those of a previously unidentified bactericidal lipid that had been detected in staphylococcal abscesses. The lipid was identified as a monoglyceride by thin layer chromatography. It resembled the unidentified lipid in that it had a high specific activity, exhibited differential activity, was inhibited by Staphylococcus aureus delta toxin, lecithin and Ca++, and its activity was reduced by oxidation. Stimulation of monoglyceride production by calcium ionophore requires the joint presence of components from the sedimented and supernatant fractions of abscess homogenates, and was not produced if boiled homogenate was used. The addition of verapamil interfered with the production of monoglyceride in homogenates treated with calcium ionophore. Monoglyceride was produced only in abscess homogenates and not in homogenates of other normal tissues or tissues taken from mice infected with S. aureus. Calcium ionophore could be replaced by inositol triphosphate, suggesting that monoglyceride production involved the release of calcium from intracellular stores. The 2 monoglyceride was the form originally produced in abscess homogenates, but this spontaneously isomerized to the 1-monoglyceride. The fatty-acid moiety of the monoglyceride consisted primarily of 16:0 and 16:1 fatty acids. PMID- 1404322 TI - Evaluation of the PhP system for biochemical-fingerprint typing of strains of Salmonella of serotype Typhimurium. AB - The Phene Plate (PhP) system of biochemical fingerprinting of bacteria is a computerised typing system, based on quantitative measurements of the kinetics of several biochemical reactions of bacteria grown in liquid medium in microtitration plates. For each isolate tested, it yields a biochemical fingerprint comprising several kinds of quantitative data which are useful for establishing similarities among strains with a personal-computer program. In this study, a set of 16 specific substrates was chosen to differentiate strains of Salmonella of serotype Typhimurium. The system was evaluated for its typability, reproducibility and discriminatory power in tests with a collection of 100 epidemiologically unrelated Typhimurium strains and results were compared with those obtained by phage typing. At an identity level of 0.980, strains were assigned by this method to 51 biochemical phenotypes (BPTs), giving a diversity index of 0.963 and a resolution index of 0.210. In contrast, 24 phage types (PTs) were identified among these isolates (a diversity index of 0.901). The combined use of biochemical fingerprinting by the PhP system and phage typing discriminated 82 phenotypes (a diversity index of 0.994). Stability of markers in each of the methods was also evaluated after subculture of 20 strains for 21 consecutive days. Only nine biochemical reactions were found that were subject to small, but measurable, changes for at least one isolate. These changes slightly decreased the mean similarity coefficients among strains but the overall BPTs of the strains showed changes in four strains (20%). In contrast, eight strains (40%) showed changes in their PTs after this treatment. It is concluded that the PhP system is a highly discriminatory and reproducible method for typing Typhimurium strains. It is easy to perform, and may be used alone or in combination with phage typing in epidemiological studies of Typhimurium strains. PMID- 1404323 TI - The use of biochemical fingerprinting, phage typing and antimicrobial susceptibility testing in the detection of epidemic strains of Salmonella of serotype Typhimurium in Iran. AB - A collection of 86 strains of Salmonella of serotype Typhimurium isolated from children with gastroenteritis in Tehran, Iran was examined for biochemical phenotype, phage type and antibiotic-resistance pattern. Twenty-seven biochemical phenotypes (BPTs), 14 discrete phage types (PTs) and 18 resistotypes (RTs) were identified. Fifty-three strains (62%) belonged to two major and probably related BPTs, whereas the other 33 isolates belonged to less common BPTs. The two predominant BPTs contained 26 strains of the same PT and 23 strains of the same RT. Different PTs and RTs of strains with similar BPT were sometimes observed, possibly reflecting antibiotic pressures in Iran. These results suggest that two major "clones" of Typhimurium strains are particularly common in Iran and, although each method alone adequately detected these and other less common "clones", biochemical fingerprinting provided additional information about relationships among strains. PMID- 1404324 TI - Treatment of experimental infections of mice with bacteriophages. AB - Bacteriophages for Acinetobacter baumanii, Pseudomonas aeruginosa and Staphylococcus aureus were tested in experimental infections of mice to investigate their potential for the treatment of infections of man. As few as 10(2) particles of an acinetobacter phage protected mice against 5 LD50 (1 x 10(8)) of a virulent strain of A. baumanii, and phage was demonstrated to have multiplied in the mice. A pseudomonas phage protected mice against 5 LD50 of a virulent strain of P. aeruginosa, with a PD50 of 1.2 x 10(7) particles. A staphylococcal phage failed to protect mice infected with a strain of S. aureus. These studies support the view that bacteriophages could be useful in the treatment of human infections caused by antibiotic-resistant strains of bacteria. PMID- 1404325 TI - Production of haemolysis and its correlation with enterotoxicity in Aeromonas spp. AB - A total of 147 clinical and environmental isolates of Aeromonas that included 14 A. hydrophila, 60 A. sobria and 73 A. caviae strains was tested for haemolysin production and its correlation with enterotoxicity; 108 isolates produced beta haemolysis. For A. hydrophila and A. sobria, titres of haemolysin were 16-128 HU/ml and for A. caviae, 16-64 HU/ml. In the ileal loop test, 82 (55.8%) strains of Aeromonas spp. produced enterotoxin. Of the beta-haemolytic strains, 72.7% of A. hydrophila, 58.6% of A. sobria and 68.6% of A. caviae isolates caused fluid accumulation in rabbit ileal loops. One strain each of alpha-haemolytic A. sobria and A. caviae, one of non-haemolytic A. sobria and nine of non-haemolytic A. caviae also caused a secretory response. The beta-haemolytic strains caused significantly more (p < 0.05) fluid accumulation than the alpha- and non haemolytic isolates regardless of their species designation. The remaining 65 (44.2%) isolates belonging to the three species included alpha-, beta- and non haemolytic strains: they failed to cause fluid accumulation in the initial experiments but did so after one to three consecutive passages through rabbit ileal loops. Two alpha- and 13 non-haemolytic strains switched to production of beta-haemolysis when they showed positive ileal loop reactions. However, on repeated subcultures or on storage in the laboratory, all of them reverted to their original haemolytic character and no longer produced enterotoxic activity. PMID- 1404326 TI - Association of Haemophilus ducreyi with cell-culture lines. AB - The association of Haemophilus ducreyi with epithelial cell cultures was studied by light microscopy, electronmicroscopy and viable counts. Associated organisms were engulfed by epithelial cells and sequestered from the cell-surface environment. Large numbers of organisms within epithelial cells appeared to induce cell lysis and release of H. ducreyi. Such a mechanism occurring in vivo may assist H. ducreyi to evade the bactericidal action of polymorphonuclear leucocytes and may explain some of the tissue damage seen in genital ulcers caused by H. ducreyi. PMID- 1404327 TI - A pyrolysis mass spectrometry study of the non-pigmented Prevotella species. AB - Collection strains (21) and non-pigmented clinical isolates (96) provisionally identified as Prevotella spp. were classified numerically on the basis of pyrolysis mass spectrometry (PMS) data and reaction patterns in conventional tests (CTRPs) for volatile and non-volatile fatty acids, pre-formed enzymes and biochemical activity. PMS and CTRP classifications were compared with a previous classification based on visual analysis of SDS-PAGE patterns. Although the order of clusters differed, cross-tabulation of cluster membership revealed strong correlations between classifications. Cluster membership in the PMS classification correlated particularly well with SDS-PAGE results. CTRP clusters corresponded largely to the recognised species of Prevotella, but PMS and SDS PAGE divided two species into sub-groups: two in P. buccae and five in P. veroralis. The latter subgroups could be discriminated by small but consistent differences in CTRPs. An undesignated, well differentiated cluster of strains appeared closest to the main group of P. buccae strains in PMS and CTRPs. B. (P.) capillus could not be distinguished from P. buccae; these species are regarded as synonymous. Strains of P. zoogleoformans and B. (P.) pentosaceus were well separated from other strains in PMS. A complex comprising clusters of P. disiens, P. oralis, P. veroralis, P. loescheii and a further undesignated group similar to P. melaninogenica was well differentiated from P. buccae and P. oris in PMS; clusters corresponding to P. bivia, P. corporis, P. intermedia and P. denticola formed another complex. PMID- 1404328 TI - Appraisal of the total blood lymphocyte proliferation assay as a diagnostic tool in screening for tuberculosis. AB - The total blood lymphocyte proliferation assay (TLP) was evaluated as a screening test for infection with Mycobacterium tuberculosis and was compared with the tuberculin (Mantoux) skin test. The results of TLP assays performed on 33 patients with tuberculosis and 37 non-tuberculous subjects were compared with results of skin tests performed in the previous year. There was a high correlation between skin test responses and TLP responses to PPD which was statistically significant. The sensitivity, specificity and the predictive value of a positive test were also similar for the skin test and TLP test. These findings suggest that the TLP test is as effective in screening for M. tuberculosis infection as tuberculin skin testing. Future research leading to further simplification of the TLP method may lead to it replacing intradermal skin testing. PMID- 1404329 TI - A simple and rapid method for the detection and identification of mycobacteria using mycobactin. AB - A system was developed for the identification of mycobacteria such as Mycobacterium tuberculosis and M. avium, by thin layer chromatography of 55Fe labelled mycobactin. Approximately 2 x 10(3) mycobacteria were detected within 24 h and little operator time or skill was required. M. avium, M. intracellulare and M. scrofulaceum were found to have lower requirements for iron than other mycobacteria and this may influence their growth in host organisms. PMID- 1404331 TI - The Universities Federation for Animal Welfare. PMID- 1404330 TI - Initial organ localisation of blood-borne Candida albicans in a rat model of disseminated candidosis. AB - The rat was evaluated as an experimental model for disseminated candidosis by quantitating blood clearance and initial organ localisation of 3H-leucine labelled Candida albicans after intravenous injection into the tail or portal vein. Viable or formalin-killed blastoconidia or viable blastoconidia with germ tubes were injected into experimental animals. Blood and tissue samples were obtained up to 24 h after injection and processed for liquid scintillation counting (to determine the distribution of labelled yeasts) and quantitation of viable organisms. Yeasts were cleared rapidly after intravenous (i.v.) injection by either route, i.e., < 5% of the radioactivity was detected in the blood after 5 min. The liver and lung were the major organs that sequestered blood-borne yeasts 1 h after tail vein injection (42.5 SD 15% and 41.4 SD 6.4% of labelled yeasts injected, respectively). However, injections via the portal vein resulted in trapping of the yeasts predominantly by the liver. Recovery of radioactivity and viable yeasts from all organs except the kidneys decreased with time. Overall, the results indicated that the rat might serve as a reliable model for short-term studies on organ distribution and thus contribute to our understanding of tissue trophism in candidosis. PMID- 1404332 TI - Determination of the time of ovulation in chimpanzees by measurement of LH, estrone sulfate, and pregnanediol 3 alpha-glucuronide in urine: comparison with serum hormone patterns. AB - The concentrations of LH, total estrogens, and pregnanediol 3 alpha-glucuronide (PdG) were determined by specific radioimmunoassays on daily overnight urine samples obtained in 13 menstrual cycles of six adult female chimpanzees during the periods of increasing, maximal, and decreasing tumescence of the perineal sex skin. The peaks of estrogens and LH and the rise in PdG in urine accurately reflected the peaks of estradiol-17 beta and LH and the subsequent rise in progesterone in the serum of the same animals during the same menstrual cycles, and can be used to predict and verify the occurrence of ovulation, thus avoiding the repeated tranquilizations necessary to obtain daily blood samples. PMID- 1404333 TI - Quantification and excretion profiles of pteridines in primate urine. AB - Biopterin, 6-hydroxymethyl-pterin, isoxanthopterin, neopterin and, pterin were quantified in stress-free collected spontaneous morning urine samples from Callithrix jacchus, Saguinus fuscicollis, Saguinus labiatus, Saimiri sciureus, Presbytis entellus, Cercopithecus albogularis, Cercocebus torquatus, Macaca fascicularis, Hylobates concolor, Pongo pygmaeus, and Gorilla gorilla. In most species, biopterin was the most frequent urinary pteridine followed by neopterin. Sex differences in biopterin and neopterin excretion were observed in Gorilla gorilla and Pongo pygmaeus. Pterin and isoxanthopterin were only present in minor concentrations. 6-hydroxymethyl-pterin was barely detectable and not present in the urine of Saguinus labiatus, Saimiri sciureus, and both male Gorilla gorilla and Pongo pygmaeus. PMID- 1404334 TI - Age determination of common marmosets (Callithrix jacchus) by radiographic examination of skeletal development. AB - Seventy-four animals were examined radiographically to determine the skeletal development of the common marmoset (Callithrix jacchus) from 6 months of age. Twenty-one epiphyses were examined and five stages of ossification were described for each. The animals were divided into nine groups, according to age, and a table of the stage of ossification and age was produced, which may be used for determining the age of animals of unknown history. PMID- 1404335 TI - The baboon model under anesthesia for in vivo cerebral blood flow studies using single photon emission computed tomographic (SPECT) techniques. AB - Single photon emission computed tomography of the brain can be useful in animal experimentation directed toward cerebral conditions. A well established and understood baboon model, necessarily under anesthesia, could be especially valuable in such investigations. Six normal baboons were studied under various anesthetic agents and their combinations: ketamine, thiopentone, pentobarbitone, and halothane. Cerebral blood flow (CBF) studies were performed with 99mTc-HMPAO. CBF effects from various anesthesia were detected, requiring careful choice of the anesthesia for cerebral investigations. PMID- 1404336 TI - Identification of two subclasses of IgA in the chimpanzee (Pan troglodytes). AB - Chimpanzee secretory immunoglobulin A (SIgA) was separated into two fractions by chromatography using the terminal galactose-binding lectin Jacalin. The SIgA fraction bound by Jacalin was cleaved by Haemophilus influenzae IgA1 protease, whereas the SIgA nonbinding fraction was not cleaved. It is proposed that these fractions represent IgA1 and IgA2 subclasses because the presence or absence of galactose-terminal oligosaccharides (Jacalin binding) and susceptibility or resistance to IgA1 protease are properties that define human IgA1 and IgA2 subclasses. PMID- 1404337 TI - Spontaneous cardiomyopathy and nephropathy in the owl monkey (Aotus sp.) in captivity. AB - Clinical and pathologic data were reviewed for 72 owl monkeys that died between January 1987 and May 1990 at the Center for Reproduction and Conservation of Nonhuman Primates in Iquitos, Peru. Tissue samples from 39 animals were examined. Hypertrophic cardiac disease (51% of animals examined), dilative cardiomyopathy (26%), and nephropathy (87%) were the most common diagnoses. The incidence of all three diseases appeared to increase with time in captivity. Nephropathy was less severe in colony-born animals. PMID- 1404338 TI - Membrane transport properties of L-2,4-diaminobutyrate revisited. AB - We explore here the special structural features of certain diamino acid analogs which may account for their intense accumulation into tumor cells, first observed for the Ehrlich ascites tumor cell for in vitro suspensions. This accumulation, which ordinarily occurs mainly by system A for its dipolar substrates, is so intense for these tripolar diamino acids accompanied by the chloride ion as well as by displacement, especially of the cellular potassium ion, that the cells swell to several times their normal volume and osmotic destruction arises. These structural features receive our reconsideration here toward understanding the energization of amino acid transport into cells, also toward identifying among them possible superior 11C-labeled tracers for imaging tumors in situ by positron emission tomography (PET). The possibility of therapeutic, perhaps osmotic, destruction of inoperable terminal gliomas by topical application of such amino acids by microdialysis has also been considered in preliminary tests by one of us (G.R.) and his associates. PMID- 1404340 TI - Sarcolemmal calcium binding sites in heart: I. Molecular origin in "gas dissected" sarcolemma. AB - Calcium in the myocardial cell is highly compartmentalized and a fast, an intermediate, a slow and a nonexchangeable calcium pool have been described. The fast pool contains 66% of the total cell exchangeable calcium in cultured neonatal rat heart cells with a t1/2 of less than 1.5 sec. Though the cellular origin of this fast pool is unknown, its rapidity and its displacement by La3+ most likely places it at the sarcolemma or at least in rapid equilibrium with the sarcolemma. We isolated the sarcolemma of cultured neonatal rat heart cells using the gas-dissection technique, which yields a pure sarcolemmal preparation in less than a second, thereby precluding membrane changes which might occur during conventional plasma membrane isolation. We determined the calcium binding characteristics of these membranes, using an on-line technique to monitor 45Ca, which allows measurement of 45Ca binding characteristics in the presence of unbound 45Ca. Two classes of calcium binding sites were determined: (i) Kd of 13 microM, capacity 7 nmol/mg and (ii) Kd of 1.1 mM, capacity of 84 nmol/mg. To assess the molecular origin of the sarcolemmal calcium binding we treated the membranes with a variety of enzymes. Protease or neuraminidase treatment did not cause large changes in these parameters. Simultaneous treatment with two different phospholipases C or the extraction of the lipids with isopropanol resulted in a dramatic loss of the low-affinity binding sites. These results, in association with previously defined sarcolemmal phospholipid distribution, places the low-affinity binding sites at the cytoplasmic leaflet. The physiological implication of this localization as it pertains to cellular calcium exchange is discussed. PMID- 1404339 TI - The structure and function of membranes--personal memoir. PMID- 1404341 TI - Sarcolemmal calcium binding sites in heart: II. Mathematical model for diffusion of calcium released from the sarcoplasmic reticulum into the diadic region. AB - We present a model for predicting the temporal and spatial dependence of [Ca] in the cardiac subsarcolemmal diadic region (cleft), following Ca release from the "feet" of the sarcoplasmic reticulum. This region is modeled as a disc 10 nm thick, 430 nm in radius, with or without Ca binding sites and open at its periphery to the cytosol. [Ca] is computed for three diffusion coefficients (100, 20 and 4% of aqueous diffusion), following release of a 20-msec square pulse sufficient to produce 50% maximal contractile force, or repetitive release (400/min) of such pulses. Numerical solutions are obtained for the general diffusion/binding problem and analytic solutions for the case of no binding sites. For the middle value of diffusion coefficient, and in the absence of binding sites, [Ca] rises to approximately 1.5 mM in 20-msec and then falls to approximately 0.1 microM in less than 3 msec. Adding binding sites reduces peak [Ca] to approximately 0.6 mM but prolongs its decline, requiring approximately 200 msec to reach 20 microM. For repetitive release [Ca] is greater than 100 microM for roughly half of each cycle. Two major implications of the predicted [Ca] are: (i) The effect of Ca binding sites on [Ca] will cause Ca efflux from the cleft via the Na-Ca exchanger (Km(Ca) approximately 20 microM) to continue at a significant level for greater than 200 msec. (ii) The time constant for inactivation of release from the "feet" must be much greater than for activation if Ca-induced Ca release is to continue for greater than 1-2 msec. PMID- 1404342 TI - Whole-cell potassium current in rabbit corneal epithelium activated by fenamates. AB - Rabbit corneal epithelium contains a large-conductance, potassium-selective channel, which is a major contributor to the whole-cell current. In perforated patch recordings of the macroscopic current, the isolated cells studied had resting voltages of -41 +/- 20 mV and capacitances of 5.8 +/- 2.6 pF (mean +/- SD for n = 255). Activation of the channels was weakly voltage dependent. They opened at about -100 mV and reached an open probability of about 0.2 at +100 mV. The current was blocked by millimolar concentrations of external Ba2+ and quinidine. Diltiazem also blocked when applied to the external surface of the membrane. Nonsteroidal anti-inflammatory agents of the fenamate group were powerful activators of the channel at submillimolar concentrations when applied either to the inside or the outside of the channels. The mechanism of action which leads to his activation is not yet known. PMID- 1404343 TI - Three-dimensional analysis of cell nucleus structures visualized by confocal scanning laser microscopy. AB - Studies of the three-dimensional (3-D) organization of cell nuclei are becoming increasingly important for the understanding of basic cellular events such as growth and differentiation. Modern methods of molecular biology, including in situ hybridization and immunofluorescence, allow the visualization of specific nuclear structures and the study of spatial arrangements of chromosome domains in interphase nuclei. Specific methods for labelling nuclear structures are used to develop computerized techniques for the automated analysis of the 3-D organization of cell nuclei. For this purpose, a coordinate system suitable for the analysis of tri-axial ellipsoidal nuclei is determined. High-resolution 3-D images are obtained using confocal scanning laser microscopy. The results demonstrate that with these methods it is possible to recognize the distribution of visualized structures and to obtain useful information regarding the 3-D organization of the nuclear structure of different cell systems. PMID- 1404344 TI - Automated microdensitometry of nucleolar organizer regions using microspectrophoto-microscopy. AB - Nucleolar organizer regions (NORs) are major sites of ribosomal RNA synthesis, providing an index of transcriptional activity and possibly determining the malignant status of cells. Difficulties lie in quantifying them. This study reports a methodology to assist in the standardization of the assessment of interphase NORs. Regenerating hepatocytes, which have increased rRNA synthesis, were chosen as a model to test automated microdensitometry for silver-stained NORs. Quantification employed a microspectrophoto-microscope as a microdensitometer. Significant differences in silver-stained NORs in hepatocytes were recorded among treatment/fixative groups. As the quantitative method avoids subjective observer error and thus improves the accuracy of measurement, it would potentially have routine application to diagnostic pathology. PMID- 1404345 TI - SEM studies of surfaces hidden within bulk tissue: a simple technique to control the position and orientation of dry fracture planes. AB - A simple, reliable method for the exposure of specific structures hidden within bulk tissue for viewing by SEM is described. The method employs dry fracture after critical-point drying and differs from other dry fracture methods in that the fracture plane is 'engineered' by the experimenter, thus overcoming the tendency for natural planes of weakness within the specimen exclusively to define the fracture plane. The technique retains the simplicity of the very high-quality in situ cellular relationships normally associated with random dry fracture. Attention is given to novel means of circumventing the artefacts that are normally a problem with dry fracture techniques. PMID- 1404346 TI - Fixation for biological ultrastructure. I. A viscometric analysis of the interaction between glutaraldehyde and bovine serum albumin. AB - The increase in viscosity resulting from mixing concentrated solutions of albumin with dilute glutaraldehyde has been investigated. The viscosity changes are slow at first, very sensitive to small changes in glutaraldehyde concentration, and non-linear with time. The cross-linking of the albumin by glutaraldehyde seems to be retarded by the weak mechanical shear forces produced by the viscometer. The significance of these findings to the events in tissue fixation is discussed. PMID- 1404347 TI - Fixation for biological ultrastructure. II. Cross-linking of bovine serum albumin by nanosecond pulses of ionizing radiation. AB - Very large doses of ionizing radiation were delivered quickly to concentrated albumin solutions by pulses of 500 keV in air. The electrons penetrated the aluminium foil bottom of the test cell and into the solution. A dose of 4.6 Mrad (4.6 x 10(4) Gy) produced a gel in the albumin solution comparable to the long term effect of 0.36% glutaraldehyde in the same albumin solution. The cross-links created by the radiation leading to gel formation are probably irreversible and quite different from those leading to gelation in the glutaraldehyde-albumin reaction. Single large pulses of ionizing radiation may be useful for fast fixation of cells and tissues for microscopy. PMID- 1404348 TI - Family support, physical impairment, and adherence in hemodialysis: an investigation of main and buffering effects. AB - Patient noncompliance is a pervasive problem among end-stage renal disease (ESRD) patients. Previous studies have implicated social support as an important correlate of adherence behavior in other chronic illness groups, but little research has examined this relationship in a hemodialysis population. The present study examined the main and interactive effects of social support in the family and illness-related physical impairment with regard to patient compliance in a sample of 78 hemodialysis patients. Results indicated that patients holding perceptions of a more supportive family environment exhibited significantly more favorable adherence to fluid-intake restrictions than did patients reporting less family support. Family support was not associated with adherence to dietary restrictions. The effect of family support on fluid-intake adherence was not moderated by level of physical impairment. This pattern suggests that the influence of support on adherence is more attributable to a main or direct effect, as opposed to a buffering process in the face of increased physical impairment. PMID- 1404349 TI - Elevated serum dehydroepiandrosterone sulfate levels in practitioners of the Transcendental Meditation (TM) and TM-Sidhi programs. AB - Serum dehydroepiandrosterone sulfate (DHEA-S) levels were measured in 270 men and 153 women who were experienced practitioners of the Transcendental Meditation (TM) and TM-Sidhi programs, mental techniques practiced twice daily, sitting quietly with the eyes closed. These were compared according to sex and 5-year age grouping to 799 male and 453 female nonmeditators. The mean DHEA-S levels in the TM group were higher in all 11 of the age groups measured in women and in 6 of 7 5-year age groups over 40 in men. There were no systematic differences in younger men. Simple regression using TM-group data revealed that this effect was independent of diet, body mass index, and exercise. The mean TM-group levels measured in all women and in the older men were generally comparable to those of nonmeditator groups 5 to 10 years younger. These findings suggest that some characteristics of TM practitioners are modifying the age-related deterioration in DHEA-S secretion by the adrenal cortex. PMID- 1404351 TI - Sex roles, occupational roles, and symptom-reporting: a test of competing hypotheses on sex differences. AB - The sick-role, fixed-role obligations, symptom-reporting, and nurturant-role hypotheses of sex differences in utilization of health services and symptom reporting were tested against each other. Fifty-one nontraditional college students completed the Cornell Medical Index (CMI), the Bem Sex Role Inventory, and questions regarding their employment status. Employment status and feminine characteristics emerged as the best predictors of symptom-reporting on the CMI and suggested that the sick-role hypothesis may be empirically superior to the others. PMID- 1404350 TI - The effects of biofeedback-assisted relaxation on cell-mediated immunity, cortisol, and white blood cell count in healthy adult subjects. AB - The effect of biofeedback-assisted relaxation on cell-mediated immunity, cortisol, and white blood cell count was investigated in healthy adults under low stress conditions. Fourteen subjects were trained with biofeedback-assisted relaxation for 4 weeks, while 17 subjects were controls. The group trained in relaxation techniques showed increased blastogenesis, decreased white blood cell count, due to decreased neutrophils, and no change in cortisol in comparison to the control group. Subjects with lower initial anxiety scores and forehead muscle tension levels showed larger increases in blastogenesis and larger decreases in neutrophils than subjects with higher initial anxiety and muscle tension levels. PMID- 1404352 TI - Adherence to exercise interventions in the treatment of hypercholesterolemia. AB - The goals of this study were to determine the rate of adherence to exercise treatment of hypercholesterolemia and to identify personality and demographic factors associated with adherence. Of the 31 subjects entering the 26-week program, 12 attended 80% or more of the scheduled sessions. Adherence was positively associated with the perceived seriousness of hypercholesterolemia, the expectation of benefit from treatment, and depressed feelings of helplessness and hopelessness. Negative associations were identified between adherence and the perception of health status being under the control of chance or of powerful others. Older subjects were more likely to be adherers at 8 and 16 weeks but not at 26 weeks. PMID- 1404353 TI - The patterning of psychological attributes and distress by "job strain" and social support in a sample of working men. AB - As a test of the "job strain" (job demands-control) model, 297 healthy men aged 30-60 were recruited at eight New York City worksites. The association among job demands and control, social support, and psychological outcomes was tested using both ANCOVA and moderated multiple regression, controlling for demographic variables. The job strain model was supported by various psychological outcome measures, with workers in "active" jobs reporting the highest level of Type A behavior, job involvement, and positive attributional style, workers in "low strain" jobs reporting the lowest job dissatisfaction and trait anxiety, workers in "passive" jobs reporting the most external locus of control and trait anxiety, and workers in "high-strain" jobs reporting the highest job dissatisfaction. Low social support was associated with greater symptomatology, and a significant three-way interaction (demands x control x support) for job dissatisfaction was observed. While selection of subjects into jobs may partially explain these findings, the results support the hypothesis that working conditions influence psychological attributes and distress. PMID- 1404354 TI - The effects of nonconcurrent and concurrent relaxation training on cardiovascular reactivity to a psychological stressor. AB - Eight patients in a cardiac rehabilitation program, after exposure to two psychological stressors approximately equivalent with respect to cardiovascular reactivity, were given nonconcurrent progressive muscle relaxation training and retested for reactivity. They were then provided with relaxation training concurrently with one of the stressors and exposed again to the two stressors. No significant effects for nonconcurrent progressive muscle relaxation training were detected. Concurrent training, in contrast, produced reductions in both systolic and diastolic blood pressure. Reductions resulting from training on the target stressor showed little tendency to generalize to the nontarget stressor; the discrimination was particularly well defined for systolic blood pressure. We conclude that muscle relaxation techniques are maximally effective in reducing reactivity to psychological stressors when relaxation training is provided concurrently with the stressor. Our findings further suggest that to inculcate the relaxation response reliably across different situations, specific training to enhance generalization may be needed. PMID- 1404355 TI - Dental visit satisfaction in a group of adults aged 50 years and over. AB - Studies have found that utilization of dental services is generally less common than utilization of medical services, particularly by older persons. Because satisfied dental patients were found to be greater users of the service than nonsatisfied patients, it was decided to investigate the correlates of dental visit satisfaction in older subjects. Predictions that satisfaction would be positively related to regular use of dental services and negatively related to dental anxiety were confirmed. The results also suggested that older dental patients have different expectations of their dentists than younger ones. PMID- 1404356 TI - Modularity of the slit protein. Characterization of a conserved carboxy-terminal sequence in secreted proteins and a motif implicated in extracellular protein interactions. AB - Since our characterization of the slit cDNA sequence, encoding a protein secreted by glial cells and involved in the formation of axonal pathways in Drosophila, we have discovered that the protein contains two additional sequence motifs that are highly conserved in a variety of proteins. A search of the GenPept database with the 73 amino acids at the carboxy terminus of slit revealed that this region contains significant similarity to a carboxy-terminal domain found in six other exported proteins. This observation has allowed us to define a new carboxy terminal protein motif. In addition, comparisons with a 202 amino acid domain residing between epidermal growth factor (EGF) repeats in slit shows this region to be conserved in laminin, agrin and perlecan and, strikingly, also to lie between EGF repeats in both agrin and perlecan. Our analysis suggests this motif is involved in mediating interactions among extracellular proteins. Consistent with our previous characterization of the slit protein, both new motifs are found only in extracellular proteins. The identification of these two conserved motifs in slit reveals that the entire 1469 amino acids of the protein are made up of modular regions similar to those conserved in other extracellular proteins. PMID- 1404357 TI - Predicting protein secondary structure with a nearest-neighbor algorithm. AB - We have developed a new method for protein secondary structure prediction that achieves accuracies as high as 71.0%, the highest value yet reported. The main component of our method is a nearest-neighbor algorithm that uses a more sophisticated treatment of the feature space than standard nearest-neighbor methods. It calculates distance tables that allow it to produce real-valued distances between amino acid residues, and attaches weights to the instances to further modify the the structure of feature space. The algorithm, which is closely related to the memory-based reasoning method of Zhang et al., is simple and easy to train, and has also been applied with excellent results to the problem of identifying DNA promoter sequences. PMID- 1404359 TI - By-passing immunisation. Human antibodies from synthetic repertoires of germline VH gene segments rearranged in vitro. AB - By display of antibody repertoires on the surface of a filamentous bacteriophage and selection of the phage by binding to antigen, we can mimic immune selection. Recently, by tapping the repertoire of rearranged V-genes from the peripheral blood lymphocytes of unimmunised donors, we succeeded in making human antibody fragments with different specificities, including both haptens and proteins, from the same library of phage. Now we have built a repertoire of human VH genes from 49 human germline VH gene segments rearranged in vitro to create a synthetic third complementarity determining region (CDR) of five or eight residues. The rearranged VH genes were cloned with a human V lambda 3 light chain as single chain Fv fragments for phage display, and the library of phage panned by binding to each of two haptens, 2-phenyl-5-oxazolone (phOx) or 3-iodo-4-hydroxy-5 nitrophenyl-acetate (NIP) coupled to bovine serum albumin (BSA). Many different antibody fragments were isolated which bound specifically to hapten, some with affinities in the micromolar range. The in vitro "immune response" to the hapten NIP was dominated by the 9-1 segment (VH3 family), and that to phOx by the VH26 segment (VH3 family) with an invariant aromatic residue (Tyr, Phe, Trp) at residue 97 of CDR3. However, the isolation of phage against protein antigens proved more elusive, with a single phage binding to human tumour necrosis factor, and none to bovine serum albumin, turkey egg-white lysozyme or human thyroglobulin. Nevertheless, the work shows that human antibody fragments with specific binding activities can be made entirely in vitro. PMID- 1404358 TI - Characterization of "native" apomyoglobin by molecular dynamics simulation. AB - We have used molecular dynamics simulation methods to study the structure and fluctuations of "native" apomyoglobin in aqueous solution for a period of greater than 0.5 nanosecond. This work was motivated by the recent attempts of Hughson et al. to characterize the structure and motion of both this molecule and the less compact, acid stabilized I stage, using methods of pulsed H/2H exchange. The study of these systems provides new insights into protein folding intermediates and our simulation has yielded a detailed model for structure and fluctuations in apomyoglobin which complements the experimental studies. We find that local (short-time) fluctuations agree well with fluctuations observed for the holoprotein in aqueous solution, as well as results from the crystallographic B factors. In addition, the structural features we observe for native apomyoglobin are very similar to the holoprotein, in basic agreement with the findings of Hughson et al. By examining larger-scale motions, developing only over timescales in excess of a 100 picoseconds, we are able to identify conformationally "labile" and "non-labile" regions within native apomyoglobin. These regions correspond extremely well to those identified in the nuclear magnetic resonance experiments as unstable and stable "folding subdomains" in the I state of apomyoglobin. Overall we find that helices A, B, E, G and H show the least amount of motion and helices C, D and F move substantially over the timescales examined. The major motions, and the primary difference between the holo and apo structures as we have observed them, are due to the shifting motion of helices C, D and F into the vacant heme cavity. We also find that motions at the interface of helical segments can be large, with one important exception being the chain segment connecting helices G and H. This segment of chain interacts with the conformationally "non-labile" helix A to form a relatively rigid subdomain composed of helices A, G and H. We believe that these findings provide direct support for the suggestion of Hughson et al. that helices A, G and H constitute a compact subdomain that remains in a native-like conformation as the protein begins to unfold in environments of decreasing pH. PMID- 1404360 TI - Prediction of the activity and stability effects of site-directed mutagenesis on a protein core. AB - When theoretical methods are used to predict the properties of a given system, such as the effects of the substitution of a specific amino acid on the activity or stability of a protein as a whole, the accuracy of the prediction is directly dependent on the validity of the underlying model. A common error, however, is to attempt to improve a basically crude model by performing one aspect of the calculation in a rigorous manner. The accuracy of the model as a whole will remain limited by the crudest approximation or weakest assumption. To demonstrate the principle that nothing can be gained by performing extensive calculations using a basically crude underlying model we compare the predictive power of three models in relation to activity and stability data for 78 triple-site sequence variants of the lambda-repressor protein. This system has recently been analysed in terms of a conceptionally simple, but computationally elaborate model for the prediction of the energy of a protein in which amino acid residues in the core of the protein have been mutated. We show that comparable, if not better agreement with the experimental data can be reached using either of two much simpler models, based on straightforward structural considerations, which do not require elaborate calculations on a computer. PMID- 1404361 TI - Structure of the TFIIIA-5 S DNA complex. AB - The missing-nucleoside experiment, a recently developed approach for determining the positions along a DNA molecule that make energetically important contacts with protein, has been used to investigate the structure of the complex of transcription factor IIIA with a somatic 5 S RNA gene from Xenopus borealis. We detect three distinct regions of the 5 S promoter that are contacted by TFIIIA, corresponding to the A-box, intermediate element and C-box regions previously identified by mutagenesis experiments. The advantage of the missing-nucleoside experiment over mutagenesis is that additional information, directly related to the structure of the complex, is obtained. Of most importance is that contacts to each strand of DNA are determined independently, and can be assigned unambiguously as interactions with TFIIIA. Throughout the binding site the strongest contacts are made with the non-coding strand of the 5 S gene. The two groups of contacts at either end of the binding site (boxes A and C) are comprised of sets of approximately ten contiguous nucleosides for which the contacts are reflected, without stagger, from one strand to the other. In contrast, contacts in the center of the promoter (the intermediate element) are staggered about five base-pairs in the 5' direction with respect to each strand. These results, when analyzed in conjunction with the hydroxyl-radical footprint of the complex, support a model in which TFIIIA wraps around the DNA in the major groove of the helix for one turn at the two ends of the complex in boxes A and C, and lies on one side of the DNA helix in the center of the complex at the intermediate element. PMID- 1404362 TI - Structure of tropomyosin at 9 angstroms resolution. AB - We have used molecular replacement followed by a highly parameterized refinement to determine the structure of tropomyosin crystals to a resolution to 9 A. The shape, coiled-coil structure and interactions of the molecules in the crystals have been determined. These crystals have C2 symmetry with a = 259.7 A, b = 55.3 A, c = 135.6 A and beta = 97.2 degrees. Because of the unusual distribution of intensity in X-ray diffraction patterns from these crystals, it was possible to solve the rotation problem by inspection of qualitative aspects of the diffraction data and to define unequivocally the general alignment of the molecules along the (332) and (3-32) directions of the unit cell. The translation function was then solved by a direct search procedure, while electron microscopy of a related crystal form indicated the probable location of molecular ends in the asymmetric unit, as well as the anti-parallel arrangement. The structural model we have obtained is much clearer than that obtained previously with crystals of extraordinarily high solvent content and shows the two alpha-helices of the coiled coil over most of the length of the molecules and establishes the coiled-coil pitch at 140(+/- 10) A. Moreover, the precise value of the coiled coil pitch varies along the molecule, probably in response to local variations in the amino acid sequence, which we have determined by sequencing the appropriate cDNA. The crystals are constructed from layers of tropomyosin filaments. There are two molecules in the crystallographic asymmetric unit and the molecules within a layer are bent into an approximately sinusoidal profile. Molecules in consecutive layers in the crystal lie at an angle relative to one another as found in crystalline arrays of actin and myosin rod. There are three classes of interactions between tropomyosin molecules in the spermine-induced crystals and these give some insights into the molecular interactions between coiled-coil molecules that may have implications for assemblies such as muscle thick filaments and intermediate filaments. In interactions within a layer, the geometry of coiled-coil contacts is retained, whereas in contacts between molecules in adjacent layers the coiled-coil geometry varies and these interactions instead appear to be dominated by the repeating pattern of charged zones along the molecule. PMID- 1404363 TI - Interchangeability of related proteins and autonomy of function. The morphogenetic proteins of filamentous phage f1 and IKe cannot replace one another. AB - The filamentous phage f1 and IKe infect a common host, are structurally highly similar and exhibit 55% identity at the DNA sequence level. Based on the idea that proteins that function autonomously will be more tolerant of multiple amino acid differences than proteins that must interact with other proteins to function, the ability of four individual proteins from f1 to substitute for their IKe equivalents to promote virus assembly in vivo has been examined. The reciprocal replacements were also examined. Only the single-strand DNA binding proteins (pV) were fully interchangeable. A minor capsid protein, pIX, was unable to substitute in assembly of the heterologous phage. Two proteins required for particle assembly that are not part of the phage particle, pI and pIV, were not interchangeable, although pIVf1 stimulated formation of a very small number of IKe particles in the absence of pIVIKe. The lack of interchangeability suggests that these morphogenetic proteins do not function autonomously, but rather interact with one or more phage proteins. The ability of certain overproduced proteins to interfere with assembly of wild-type f1 or IKe forms the basis for a model that suggests that phage assembly requires an interaction between pI and pIV. PMID- 1404364 TI - Mutational analysis of the "slippery-sequence" component of a coronavirus ribosomal frameshifting signal. AB - The ribosomal frameshift signal in the genomic RNA of the coronavirus IBV is composed of two elements, a heptanucleotide "slippery-sequence" and a downstream RNA pseudoknot. We have investigated the kinds of slippery sequence that can function at the IBV frameshift site by analysing the frameshifting properties of a series of slippery-sequence mutants. We firstly confirmed that the site of frameshifting in IBV was at the heptanucleotide stretch UUUAAAC, and then used our knowledge of the pseudoknot structure and a suitable reporter gene to prepare an expression construct that allowed both the magnitude and direction of ribosomal frameshifting to be determined for candidate slippery sequences. Our results show that in almost all of the sequences tested, frameshifting is strictly into the -1 reading frame. Monotonous runs of nucleotides, however, gave detectable levels of a -2/+1 frameshift product, and U stretches in particular gave significant levels (2% to 21%). Preliminary evidence suggests that the RNA pseudoknot may play a role in influencing frameshift direction. The spectrum of slip-sequences tested in this analysis included all those known or suspected to be utilized in vivo. Our results indicate that triplets of A, C, G and U are functional when decoded in the ribosomal P-site following slippage (XXXYYYN) although C triplets were the least effective. In the A-site (XXYYYYN), triplets of C and G were non-functional. The identity of the nucleotide at position 7 of the slippery sequence (XXXYYYN) was found to be a critical determinant of frameshift efficiency and we show that a hierarchy of frameshifting exists for A site codons. These observations lead us to suggest that ribosomal frameshifting at a particular site is determined, at least in part, by the strength of the interaction of normal cellular tRNAs with the A-site codon and does not necessarily involve specialized "shifty" tRNAs. PMID- 1404365 TI - X-ray diffraction study of di and tetra-ligated T-state hemoglobin from high salt crystals. AB - X-ray diffraction difference electron density maps at 3 A resolution obtained from di and tetra-ligated T-state hemoglobin (Hb) crystals are reported. Crystals isomorphous with native deoxyhemoglobin were obtained from ammonium sulfate solutions incubated with the synthetic allosteric effector RSR-56. RSR-56 binds at two symmetry-related Hb central water cavity sites and each molecule has major interactions with three different subunit side-chains; one effector with Arg141 alpha 2 HC3, Lys99 alpha 1 G6 and Asn108 beta 1 and the other with the symmetry related residues, Arg141 alpha 1 Lys99 alpha 2 and Asn108 beta 2. Crystals mounted in a nitrogen filled glove box were di-ligated as previously found with polyethyleneglycol Hb crystals. Crystals mounted in air under a layer of mother liquor were bright red and showed all four heme groups ligated. The difference electron density from the di-ligated crystals showed atomic movements to be restricted to the immediate neighborhood of the heme groups and the allosteric effector. By contrast, the tetra-ligated structure showed extended difference electron density near amino acid residues around both alpha and beta heme groups and along the alpha 1/beta 2 interface. Ligation of the beta heme group appears to magnify the difference density around the alpha heme groups. There is no evidence of breakage of the Bohr salt bridge, His146 beta HC3----Asp94 beta FG1, in the crystal. The observed difference electron density maps may help to clarify the way the allosteric mechanism is triggered. PMID- 1404366 TI - Solution structure of a DNA octamer containing the Pribnow box via restrained molecular dynamics simulation with distance and torsion angle constraints derived from two-dimensional nuclear magnetic resonance spectral fitting. AB - The DNA octamer [d(GTATAATG].[(CATATTAC)], containing the prokaryotic upstream consensus recognition sequence, has been examined via proton homonuclear two dimensional nuclear Overhauser effect (2D NOE) and double-quantum-filtered correlation (2QF-COSY) spectra. All proton resonances, except those of H5' and H5" protons, were assigned. A temperature dependence study of one-dimensional nuclear magnetic resonance (NMR) spectra, rotating frame 2D NOE spectroscopy (ROESY), and T1 rho measurements revealed an exchange process that apparently is global in scope. Work at lower temperatures enabled a determination of structural constraints that could be employed in determination of a time-averaged structure. Simulations of the 2QF-COSY cross-peaks were compared with experimental data, establishing scalar coupling constant ranges of the individual sugar ring protons and hence pucker parameters for individual deoxyribose rings. The rings exhibit a dynamic equilibrium of N and S-type conformers with 80 to 100% populations of the latter. A program for iterative complete relaxation matrix analysis of 2D NOE spectral intensities, MARDIGRAS, was employed to give interproton distances for each mixing time. According to the accuracy of the distance determination, upper and lower distance bounds were chosen. The distance bounds define the size of a flat-well potential function term, incorporated into the AMBER force-field, which was employed for restrained molecular dynamics calculations. Torsion angle constraints in the form of a flat-well potential were also constructed from the analysis of the sugar pucker data. Several restrained molecular dynamics runs of 25 picoseconds were performed, utilizing 184 experimental distance constraints and 80 torsion angle constraints; three different starting structures were used: energy minimized A-DNA, B-DNA, and wrinkled D-DNA, another member of the B-DNA family. Convergence to similar structures obtained with root-mean-square deviations between resulting structures of 0.37 to 0.92 A for the central hexamer of the octamer. The average structure from the nine different molecular dynamics runs was subjected to final restrained energy minimization. The resulting final structure was in good agreement with the structures derived from different molecular dynamics runs and exhibited a substantial improvement in the 2D NOE sixth-root residual index in comparison with the starting structures. An approximation of the structure in the terminal base-pairs, which displayed experimental evidence of fraying, was made by maintaining the structure of the inner four base-pairs and performing molecular dynamics simulations with the experimental structural constraints observed for the termini.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1404367 TI - Loop mutations can cause a substantial conformational change in the carboxy terminus of the ferritin protein. AB - Although some protein folding theories sustain that the peptides (loops) that connect elements of more compact secondary structure may be important in the folding process, most of the data accumulated until now seems to contradict this notion. To approach this problem we have isolated and characterized a number of mutants in which the amino acid sequence of the peptide that connects helix D and helix E in the H-chain of human ferritin has been randomized. Our results indicate that, though no single loop residue is absolutely required for ferritin to attain the native conformation, most of the mutants that we have obtained by random regional mutagenesis, affect its folding/assembly process. This conclusion was reached utilizing a sensitive test that associates the color formed by a colony synthesizing a hybrid ferritin-beta-galactosidase protein to the ability of the ferritin domain to fold and assemble as the native protein. The characterization of the folding/assembly properties of our collection of mutants and the comparison of the mutant loop sequences, have allowed us to draw the following conclusions. Mutants that have positively charged residues at position 159, 160 or 161 fail to assemble into the native protein shell and form an insoluble aggregate. Interestingly some loop amino acid sequences cause the E helix to reverse direction and to expose its COOH group, normally hidden inside the protein cavity, to the solvent. The propensity of a given ferritin mutant to fold into this "non-native" conformation can be attenuated by the introduction of Gly at position 159 and 164, as in the natural ferritin. PMID- 1404368 TI - Alpha-helix stability in proteins. I. Empirical correlations concerning substitution of side-chains at the N and C-caps and the replacement of alanine by glycine or serine at solvent-exposed surfaces. AB - The importance of amino acid side-chains in helix stability has been investigated by making a series of mutations at the N-caps, C-caps and internal positions of the solvent-exposed faces of the two alpha-helices of barnase. There is a strong positional and context dependence of the effect of a particular amino acid on stability. Correlations have been found that provide insight into the physical basis of helix stabilization. The relative effects of Ala and Gly (or Ser) may be rationalized on the basis of solvent-accessible surface areas: burial of hydrophobic surface stabilizes the protein as does exposure to solvent of unpaired hydrogen bond donors or acceptors in the protein. There is a good correlation between the relative stabilizing effects of Ala and Gly at internal positions with the total change in solvent-accessible hydrophobic surface area of the folded protein on mutation of Ala----Gly. The relationship may be extended to the N and C-caps by including an extra term in hydrophilic surface area for the solvent exposure of the non-intramolecularly hydrogen-bonded main-chain CO, NH or protein side-chain hydrogen bonding groups. The requirement for solvent exposure of the C-cap main-chain CO groups may account for the strong preference for residues having positive phi and psi angles at this position, since this alpha L conformation results in the largest solvent exposure of the C-terminal CO groups. Glycine in an alpha L-conformation results in the greatest exposure of these CO groups. Further, the side-chains of His, Asn, Arg and Lys may, with positive phi and psi-angles, form a hydrogen bond with the backbone CO of residue in position C -3 (residues are numbered relative to the C-cap). The preferences at the C-cap are Gly much greater than His greater than Asn greater than Arg greater than Lys greater than Ala approximately Ser approximately greater than Asp. The preferences at the N-cap are determined by hydrogen bonding of side-chains or solvent to the exposed backbone NH groups and are: Thr approximately Asp approximately Ser greater than Gly approximately Asn greater than Gln approximately Glu approximately His greater than Ala greater than Val much greater than Pro. These general trends may be obscured when mutation allows another side-chain to become a surrogate cap.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1404369 TI - Alpha-helix stability in proteins. II. Factors that influence stability at an internal position. AB - The solvent-exposed residue Ala32 in the second alpha-helix of barnase was replaced by all other naturally occurring amino acids and the concomitant effects on the protein stability were determined. The results are assumed to reflect both the distinct conformational preferences of the different amino acids and also possible intrahelical interactions. The conformational preferences may be fully rationalized by invoking only a few physical principles. The results agree well with recently experimentally determined rank-order of helix-forming tendencies determined on a model peptide. There is very weak correlation between the results and the experimental host-guest values. There is a weak correlation between our results and the statistical helix propensities and a slightly better correlation with the positional-dependent statistical parameters of J. S. Richardson, and D. C. Richardson. PMID- 1404370 TI - Crystallization and preliminary crystallographic data of a Streptomyces scabies extracellular esterase. AB - X-ray quality single crystals of an extracellular esterase from pathogenic Streptomyces scabies were obtained by the hanging drop method. The crystals are monoclinic (space group C2, a = 161.1 A, b = 51.2 A, c = 124.2 A, beta = 100.6 degrees) with two molecules related by a noncrystallographic dyad in the asymmetric unit, with a solvent content of approximately 64%. The diffraction pattern from fresh crystals extends beyond 2 A resolution using sealed tube CuK alpha radiation. The study has been initiated in order to elucidate the mechanism of this unusual non-serine-dependent esterase, and to gain better understanding of the molecular basis of the pathogenesis of the scab disease. PMID- 1404371 TI - Expression, purification and crystallization of the Vibrio harveyi acyltransferase. AB - We have obtained X-ray quality single crystals of Vibrio harveyi acyltransferase. The protein was obtained from V. harveyi by a gene mobilization expression system. The crystals are monoclinic (space group P2(1), a = 89.9 A, b = 83.6 A, c = 47.1 A, beta = 97.3 degrees) with two molecules related by a pronounced non crystallographic dyad in the asymmetric unit, with a solvent content of approximately 50%. The diffraction pattern from fresh crystals extends beyond 2 A resolution using sealed tube CuK alpha radiation. The elucidation of the three dimensional structure of this enzyme, believed to contain a proteinase-like catalytic triad, which resembles in many ways other eukaryotic fatty acid chain terminating enzymes, may have important consequences for our understanding of the molecular basis of the final stages of the synthesis of fatty acids. PMID- 1404373 TI - Crystallization of human beta-hexosaminidase B. AB - beta-Hexosaminidase is a lysosomal hydrolase that is important in the metabolism of sphingoglycolipids. beta-Hexosaminidase B and beta-hexosaminidase A are the major isozymes in normal human tissue. beta-Hexosaminidase B is a homodimer of beta subunits, and beta-hexosaminidase A is a heterodimer composed of an alpha and a beta subunit. Crystals of beta-hexosaminidase B (M(r) 112,000) have been grown using the handling drop technique. They are elongated hexagonal prisms with maximum dimensions of 0.2 mm x 0.2 mm x 0.7 mm. The space group is P6(1)22 (or enantiomorph); the unit cell dimensions are a = b = 114.2 A, c = 402.2 A, alpha = beta = 90 degrees, gamma = 120 degrees. The molecular mass and cell dimensions suggest that there is one dimer per asymmetric unit. Crystals diffract to 3.2 A resolution. PMID- 1404372 TI - Preliminary crystallographic analyses of the N-terminal lobe of recombinant human serum transferrin. AB - The N-terminal lobe of recombinant human serum transferrin (residues 1 to 337) has been crystallized in a form suitable for high-resolution three-dimensional X ray crystallographic analyses. Crystals are of the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions of a = 44.9 A, b = 57.0 A and c = 135.9 A, and diffract to beyond 2 A resolution. Further studies show that isomorphous crystals of specifically designed mutants of this protein can also be grown. Structural studies of both recombinant and mutant protein forms will provide a basis for understanding the mechanism by which human serum transferrin functions. PMID- 1404374 TI - Crystallization and preliminary X-ray crystallographic studies of rusticyanin from Thiobacillus ferrooxidans. AB - Rusticyanin is a 16.5 kDa type I blue copper protein isolated from Thiobacillus ferrooxidans. This organism can grow on Fe2+ as its sole energy source. Rusticyanin is thought to be a principal component in the iron respiratory electron transport chain of T. ferrooxidans. As a component of the periplasmic space of an acidophilic bacterium, rusticyanin is remarkably stable at acidic pH. It is redox-active down to pH 0.2. Crystals of rusticyanin have been grown from solutions of PEG 8000 by the hanging-drop vapor diffusion method. The crystals are orthorhombic, space group P2(1)2(1)2(1), with unit cell dimensions a = 32.36 A, b = 60.37 A, c = 74.60 A. The crystals diffract to 2.0 A resolution and they are stable in the X-ray beam for at least two days. PMID- 1404375 TI - Crystallization and preliminary X-ray analysis of the methane monooxygenase hydroxylase protein from Methylococcus capsulatus (Bath). AB - Methane monooxygenase is a multicomponent enzyme system that catalyzes the conversion of methane to methanol in methanotrophic bacteria. Catalysis occurs at non-heme dinuclear iron centers contained in the hydroxylase component of the system, a dimer of composition alpha 2 beta 2 gamma 2. The hydroxylase protein from Methylococcus capsulatus (Bath) has been crystallized from aqueous solutions containing polyethylene glycol, lithium sulfate, and ammonium acetate. The crystals are orthorhombic, space group P2(1)2(1)2(1), with one dimer of relative molecular mass M(r) = 252,000 in the asymmetric unit. The unit cell dimensions are a = 62.6 A, b = 110.1 A, c = 333.5 A. The crystals diffract uniformly beyond 2.5 A resolution. Crystals of the related hydroxylase from Methylosinus trichosporium OB3b have also been obtained. PMID- 1404376 TI - Three different but related gene clusters encoding gas vesicles in halophilic archaea. AB - We present an analysis of the chromosomal region comprising the gene cluster involved in gas vesicle (Vac) synthesis in Haloferax mediterranei (mc-vac-region) and Halobacterium salinarium (c-vac-region) and compare both of them to the plasmid located p-vac-region of H. salinarium. The p-vac-region of 9000 base pairs (9 kb) is more related to mc-vac (9.4 kb) of Hf. mediterranei than it is to the c-vac-region (8.3 kb) present in the same cell. The Vac- species Hf. volcanii becomes Vac+ following transformation with a fragment containing the entire mc vac-region. Also the p-vac-region transforms Hf. volcanii to a Vac+ phenotype, indicating that this gene cluster is sufficient for gas vesicle synthesis and does not depend on products of the c-vac-region. Each of these vac-regions contains, in addition to gvpA encoding the major gas vesicle protein, 13 open reading frames named gvpC through gvpO. Ten of these, gvpD through gvpM, are located upstream from gvpA in opposite orientation, while gvpC, gvpN and gvpO are found 3' to gvpA. The absolute requirement of gvpO for gas vesicle synthesis was demonstrated by transformation experiments. Northern analyses with RNA samples isolated during the growth cycle of Hf. mediterranei or of H. salinarium PHH4 revealed that the mc-gvpD or c-gvpD mRNAs occur similar to the respective gvpA mRNA in stationary growth phase, while gvpF-gvpM are transcribed mainly during logarithmic growth. S1-nuclease mapping was performed to determine the transcriptional start site of the gvpD mRNA. The distance between the two divergent start sites of gvpA and gvpD mRNA is 109 base-pairs in mc-vac and p vac, while in the case of c-vac this distance is 22 base-pairs larger. The conservation of the various gvp products, characteristic features and their possible functions in gas vesicle synthesis are discussed. PMID- 1404377 TI - Occurrence of an actin-inserting domain in tensin. AB - We have previously described a protein called "insertin" that binds strongly to barbed ends of actin filaments and permits polymerization of actin filaments by insertion of actin monomers between the barbed ends and barbed end-bound insertin. We determined the amino acid sequence of insertin and found that the primary structure of insertin is almost identical to amino acid residues 862 to 1212 of the actin-binding protein tensin. PMID- 1404378 TI - Mutation in the specificity polypeptide of the type I restriction endonuclease R.EcoK that affects subunit assembly. AB - We describe the isolation and characterization of a temperature-sensitive mutation within the hsdS gene of the type I restriction and modification system EcoK. This mutation appears to affect the ability of the HsdR subunit to interact with the HsdS subunit when forming an active endonuclease. We discuss the possibility that this mutant, together with another mutation described previously, may define a discontinuous domain, involved in protein-protein interactions, within the HsdS polypeptide. PMID- 1404379 TI - Role of integration host factor in stimulating transcription from the sigma 54 dependent nifH promoter. AB - In a wide variety of nitrogen-fixing organisms among the Purple Bacteria (large division of Gram-negative bacteria) the nitrogen fixation (nif) operons are transcribed by an alternative holoenzyme form of RNA polymerase, sigma 54 holoenzyme. Transcription depends on the activator protein NIFA (nitrogen fixation protein A), which catalyzes isomerization of closed complexes between this polymerase and a promoter to transcriptionally productive open complexes. NIFA-mediated activation of transcription from the nifH promoter of Klebsiella pneumoniae is greatly stimulated by the integration host factor IHF, which binds to a site between the upstream binding site for NIFA and the promoter, and bends the DNA. IHF fails to stimulate activation of transcription from this promoter by another activator of sigma 54-holoenzyme, NTRC (nitrogen regulatory protein C), which lacks a specific binding site in the nifH promoter region. As predicted, if the IHF-induced bend facilitates interaction between NIFA and sigma 54 holoenzyme, substitution of an NTRC-binding site for the NIFA-binding site allowed IHF to stimulate NTRC-mediated activation of transcription from the nifH promoter. The stimulation was of the same order of magnitude as that for NIFA in the native configuration of the promoter-regulatory region (up to 20-fold). With purified NTRC and the substitution construct we could demonstrate that stimulation by IHF in a purified transcription system was comparable to that in a crude coupled transcription-translation system, indicating that the stimulation in the crude system could be accounted for by IHF. The IHF stimulation was observed on linear as well as supercoiled templates, indicating that the geometric requirements are relatively simple. We have attempted to visualize the arrangement of proteins on DNA fragments carrying the nifH promoter-regulatory region of K. pneumoniae by electron microscopy. IHF stimulated NIFA-mediated activation of transcription from the nifH and nifD promoters of Bradyrhizobium japonicum and less so from the nifH promoters of Rhizobium meliloti and Thiobacillus ferrooxidans, consistent with previous observations that stimulation is greatest at promoters that are weak binding sites for sigma 54-holoenzyme in closed complexes. PMID- 1404380 TI - Limited proteolysis unmasks specific DNA-binding of the murine RNA polymerase I specific transcription termination factor TTFI. AB - Previously we have shown that nuclear extracts from mouse cells contain a heterogeneous group of polypeptides (p65, p80, p90, p100) which form distinct DNA protein complexes on the 18 base-pair sequence element (termed Sal-box), which constitutes the murine rDNA transcription termination signal. These distinct proteins mediate cessation of RNA polymerase I (pol I) transcription elongation and release of the nascent RNA chains, indicating that they function as termination factor(s). Here, we report the biochemical analysis of the pol I specific transcription termination factor TTFI. We show that the heterogeneity of TTFI is due to limited proteolysis of a larger, 130 kDa precursor protein (p130). The DNA-binding activity of p130 is strongly reduced as compared to the proteolytic derivatives, indicating that the DNA-binding domain is repressed within the full-length molecule. We have used limited proteolysis to purify and functionally characterize a TTFI core polypeptide (p50) which still specifically binds to the Sal-box target sequence and directs rDNA transcription termination. The equilibrium constant of purified p50 to bind specifically to DNA is 9 x 10(9) M-1. Additionally, we demonstrate that TTFI binds to DNA as a monomer and that binding induces DNA bending. This observation suggests that not only specific DNA protein and protein-protein interactions but also conformational alterations of DNA may play a role in the termination process. PMID- 1404381 TI - Definition and polarity of action of DNA replication terminators in Bacillus subtilis. AB - The first stage in termination of chromosome replication in Bacillus subtilis involves arrest of the clockwise fork at the inverted repeat region (IRR), comprising the opposed IRI and IRII sequences, adjacent to the upstream region of the rtp gene, which encodes the replication terminator protein RTP. RTP binds to IRI and IRII. The ability of the IRR and its components to function as terminators, in conjunction with RTP, and their polarity of action have now been tested by the use of plasmids replicating in B. subtilis as unidirectional theta structures and into which potential terminator sequences were inserted in alternate orientations relative to fork movement. When the complete IRR was inserted into such plasmids and the new plasmids transferred into a B. subtilis strain overproducing RTP, it was able to block movement of a replication fork approaching from either direction. IRI and IRII were shown to function as polar terminators, each blocking movement of a fork when it approached from one particular direction but not the other. Furthermore, the polarity of action was in accordance with the IRR being able to operate as a replication fork trap. Thus, a fork approaching the IRR would pass through the first terminator encountered (IRI or IRII) and be halted by the second. The previously observed nonfunctioning of a particular orientation of chromosomal IRR as a fork arrest site probably reflects a limiting level of RTP in the cell. Interestingly, a 21 base-pair core sequence spanning a single RTP binding site within IRI (the 47 base-pair IRI contains 2 binding sites) was unable to arrest a fork approaching from either direction in the plasmid system. This suggests that both binding sites within an IR must be filled in order to function as an arrest site. It is possible that co-operative interaction between adjacent dimers within IRI or IRII provides the necessary conformation for causing fork arrest. PMID- 1404382 TI - Molecular cloning and analysis of the gene encoding the NADH oxidase from Streptococcus faecalis 10C1. Comparison with NADH peroxidase and the flavoprotein disulfide reductases. AB - The gene encoding the streptococcal flavoprotein NADH oxidase (NOXase), which catalyzes the four-electron reduction of O2-->2H2O, has been cloned and sequenced from the genome of Streptococcus (Enterococcus) faecalis 10C1 (ATCC 11700). The deduced NOXase protein sequence corresponds to a molecular mass of 48.9 kDa and contains three previously sequenced cysteinyl peptides obtained with the purified enzyme. In Escherichia coli, the expressed nox gene produced a catalytically active product, which retained its immunoreactivity to affinity-purified NOXase antisera. Alignment of the NOXase protein sequence with that of streptococcal NADH peroxidase (NPXase) revealed that the proteins are 44% identical. Among the most highly conserved segments is a sequence containing Cys42; this residue is known to exist as a stabilized cysteine-sulfenic acid (Cys-SOH) in NPXase and serves as the non-flavin redox center. In addition, three previously identified NPXase segments, known to be involved in FAD and NAD(P)-binding in other pyridine nucleotide-linked flavoprotein oxidoreductases, are strongly conserved in NOXase. Overall, the extensive homology observed between NOXase and NPXase suggests that the monomer chain fold of the oxidase closely resembles that of the peroxidase. Both sequences share limited but significant homology to those of glutathione reductase and other members of the flavoprotein disulfide reductase family. These and other considerations suggest that these two unusual streptococcal flavoproteins constitute a distinct class of FAD-dependent oxidoreductases, the flavoprotein peroxide reductases, easily contrasted with enzymes such as glutathione reductase and thioredoxin reductase. PMID- 1404383 TI - M ring, S ring and proximal rod of the flagellar basal body of Salmonella typhimurium are composed of subunits of a single protein, FliF. AB - The flagellar basal body, a major part of the flagellar motor, consists of a rod and four rings. When the fliF gene of Salmonella typhimurium, which was previously shown to code for the component protein of the M ring, was cloned and overexpressed in Escherichia coli, the FliF subunits formed ring structures in the cytoplasmic membrane. Electron microscopic observation of the purified ring structures revealed that each was composed of two adjacent rings and a short appendage extending from the center of the rings. Antibodies raised against the purified FliF protein decorated both the M and S rings of the intact basal body. We conclude that the FliF protein is the subunit protein of the M ring, and of the S ring and of part of the proximal rod of the flagellar basal body. PMID- 1404384 TI - Structure of striated microtubule-associated fibers of flagellar roots. Comparison of native and reconstituted states. AB - Several fiber systems are associated with the flagella and basal bodies of eukaryotic cells. Apart from the contractile and Ca(2+)-sensitive system-II fibers, these include the noncontractile system-I fibers that run parallel to flagellar root microtubules. Using electron microscopy and image reconstruction, we have investigated the structure of the system-I fibers of the flagellate green alga Spermatozopsis similis. The fibers were observed in three different states: (1) in situ, (2) after isolation of the intact fibers, (3) after disassembly and reconstitution of fibers in vitro from their 34 kDa subunit protein. The fibers are highly ordered; they show a constant repeat of 28 nm, they are polar, and they contain several transverse and longitudinal striations. A model is discussed showing the system-I fiber to be built from rod-like molecules with a staggered arrangement and identical polarities. PMID- 1404385 TI - Simplified methods for construction, assessment and rapid screening of peptide libraries in bacteriophage. AB - An efficient strategy has been devised for the construction of diverse peptide libraries in bacteriophage vectors. This strategy was used to generate a library of 4 x 10(8) random decapeptide inserts in the pIII protein of bacteriophage fd. A novel method for evaluating the genetic diversity of bacteriophage libraries based on colony hybridization with partially degenerate oligonucleotides has been developed. The decapeptide library was affinity-selected with a previously characterized monoclonal antibody specific for the V3 loop of the gp120 protein of HIV-1. Immunological screening, an efficient technique for the rapid identification of putative binding bacteriophage, is described. Hexapeptide sequences similar to those obtained from affinity selection of a hexapeptide bacteriophage library were obtained from the decapeptide library in all five frames. Immunological screening of 20,000 clones from the two libraries after two rounds of affinity selection rapidly identified antibody-binding sequences; 93% and 86% of the sequences obtained from the hexapeptide and decapeptide libraries, respectively, had IC50 values < or = 10 mM as free peptides. PMID- 1404386 TI - Structural requirements for viroid processing by RNase T1. AB - Viroids are replicated via a rolling circle-like mechanism in which (+) strand oligomeric intermediates have to be cleaved enzymatically to unit-length molecules followed by ligation to mature circles. A transcript of potato spindle tuber viroid, which is still infectious, consists of a monomeric molecule with only 22 additional nucleotides, thus doubling part of the central conserved region of viroids. It was shown that this transcript can be cleaved and ligated in vitro to circles by RNase T1. To elucidate the site and mechanism of processing, 16 different site-specific mutants of this longer-than-unit-length transcript were constructed and analyzed by in vitro processing with RNase T1, infectivity studies, temperature-gradient gel electrophoresis, and structure calculations. The wild-type sequence and several mutated transcripts are able to adopt a particular secondary structure which is the prerequisite for enzymatic cleavage and ligation by RNase T1. This "processing structure" exposes both potential cleavage sites in the nearest spatial neighborhood, thus favoring the subsequent ligation to circles. Those mutated sequences for which the formation of the processing structure is impossible or thermodynamically highly unfavored are not processed. The results demonstrate that the particular structural features of viroids enable them to be cleaved and ligated by one and the same enzyme, RNase T1. The in vitro mechanism may serve as a mechanistic model for cellular processing of viroids. PMID- 1404387 TI - Crystal and molecular structure of the A-DNA dodecamer d(CCGTACGTACGG). Choice of fragment helical axis. AB - The crystal structure of the dodecamer d(CCGTACGTACGG) has been determined at 2.5 A resolution. The crystals grow in the hexagonal space group P6(1)22, a = b = 46.2 A, c = 71.5 A with one strand as the asymmetric unit. Diffraction data were collected by the oscillation film method yielding 1664 unique reflections with an Rmerge of 0.04. The structure was solved by real-space rotational translational searches with idealized helical models of A, B and Z-DNA. The best agreement was given by an A-DNA model with its dyad axis along the diagonal crystallographic dyad axis, with an R-factor 0.43 and correlation coefficient of 0.59 for data between 10 and 5 A. Iterative map fitting and restrained least-squares refinement and addition of 40 solvent molecules brought the R-factor to 0.15 and the correlation coefficient to 0.97 for all data between 8.0 and 2.5 A. The stereochemistry of the atomic model is good, with a root-mean-square deviation in bond distances of 0.006 A. This is the first example of an A-DNA containing a full helical turn. The dodecamer displays a novel packing motif. In addition to the characteristic contacts between the terminal base-pairs and the minor grooves of symmetry-related molecules, there are also minor groove to minor groove interactions not previously observed. The packing leaves an approximately 25 A diameter solvent channel around the origin, along the c-axis. The presence of a prominent 3.4 A meridional reflection and other diffuse features in the diffraction pattern provided evidence for the presence of disordered B-DNA along the c-axis, which can be accommodated in these solvent channels. The molecular conformation of the dodecamer also displays novel features. The dyad-related halves of the molecule are bent at an angle of 20 degrees, and the helical parameters are affected by this bend. Unlike the shorter A-DNA octamers, the dimensions of the major groove can be directly measured. Novel correlations between local helical parameters and global conformational features are presented. Most of the solvent molecules are associated with the major groove and the sugar-phosphate backbone. PMID- 1404388 TI - The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops. AB - We have used the polymerase chain reaction and VH family-based primers to clone and sequence 74 human germline VH segments from a single individual and built a directory to include all known germline sequences. The directory contains 122 VH segments with different nucleotide sequences, 83 of which have open reading frames. The directory indicates that the structural diversity of the germline repertoire for antigen binding is fixed by about 50 groups of VH segments: each group encodes identical hypervariable loops. The directory should help in mapping the VH locus, in estimating somatic mutation and VH segment usage and in designing and constructing synthetic antibody libraries. PMID- 1404389 TI - Structural repertoire of the human VH segments. AB - The VH gene segments produce the part of the VH domains of antibodies that contains the first two hypervariable regions. The sequences of 83 human VH segments with open reading frames, from several individuals, are currently known. It has been shown that these sequences are likely to form a high proportion of the total human repertoire and that an individual's gene repertoire produces about 50 VH segments with different protein sequences. In this paper we present a structural analysis of the amino acid sequences produced by the 83 segments. Particular residue patterns in the sequences of V domains imply particular main chain conformations, canonical structures, for the hypervariable regions. We show that, in almost all cases, the residue patterns in the VH segments imply that the first hypervariable regions have one of three different canonical structures and that the second hypervariable regions have one of five different canonical structures. The different observed combinations of the canonical structures in the first and second regions means that almost all sequences have one of seven main-chain folds. We describe, in outline, structures of the antigen binding site loops produced by nearly all the VH segments. The exact specificity of the loops is produced by (1) sequence differences in their surface residues, particularly at sites near the centre of the combining site, and (2) sequence differences in the hypervariable and framework regions that modulate the relative positions of the loops. PMID- 1404390 TI - The crystal and molecular structure of the Rhizomucor miehei triacylglyceride lipase at 1.9 A resolution. AB - The crystal and molecular structure of a triacylglyceride lipase (EC 3.1.1.3) from the fungus Rhizomucor miehei was analyzed using X-ray single crystal diffraction data to 1.9 A resolution. The structure was refined to an R-factor of 0.169 for all available data. The details of the molecular architecture and the crystal structure of the enzyme are described. A single polypeptide chain of 269 residues is folded into a rather unusual singly wound beta-sheet domain with predominantly parallel strands, connected by a variety of hairpins, loops and helical segments. All the loops are right-handed, creating an uncommon situation in which the central sheet is asymmetric in that all the connecting fragments are located on one side of the sheet. A single N-terminal alpha-helix provides the support for the other, distal, side of the sheet. Three disulfide bonds (residues 29-268, 40-43, 235-244) stabilize the molecule. There are four cis peptide bonds, all of which precede proline residues. In all, 230 ordered water molecules have been identified; 12 of them have a distinct internal character. The catalytic center of the enzyme is made up of a constellation of three residues (His257, Asp203 and Ser144) similar in structure and function to the analogous (but not homologous) triad found in both of the known families of serine proteinases. The fourth residue in this system equivalent to Thr/Ser in proteinases), hydrogen bonded to Asp, is Tyr260. The catalytic site is concealed under a short amphipatic helix (residues 85 to 91), which acts as "lid", opening the active site when the enzyme is adsorbed at the oil-water interface. In the native enzyme the "lid" is held in place by hydrophobic interactions. PMID- 1404391 TI - X-ray structure determination of telokin, the C-terminal domain of myosin light chain kinase, at 2.8 A resolution. AB - The three-dimensional structure of telokin, an acidic protein identical to the C terminal portion of smooth muscle myosin light chain kinase from turkey gizzard, has been determined at 2.8 A resolution and refined to a crystallographic R factor of 19.5% for all measured X-ray data from 30 A to 2.8 A. Crystals used in the investigation belonged to the space group P3(2)21, with one molecule per asymmetric unit and unit cell dimensions of a = b = 64.4 A and c = 50.6 A. Telokin contains 154 amino acid residues, 103 of which were visible in the electron density map. The overall molecular fold of telokin consists of seven strands of antiparallel beta-pleated sheet that wrap around to form a barrel. There is also an extended tail of eight amino acid residues at the N terminus that does not participate in beta-sheet formation. The beta-barrel can be simply envisioned as two layers of beta-sheet, nearly parallel to one another, with one layer containing four and the other three beta-strands. This type of beta-barrel, as seen in telokin, was first observed for the CH2 domain of an immunoglobulin fragment Fc. Telokin is an intracellular protein and, as such, does not contain the disulphide linkage between beta-strands B and F normally observed in the immunoglobulin constant domains. It does, however, contain two cysteine amino acid residues (Cys63 and Cys115) that are situated at structurally identical positions to those forming the disulphide linkage in the immunoglobulin constant domain. PMID- 1404392 TI - Contact potential that recognizes the correct folding of globular proteins. AB - We have devised a continuous function of interresidue contacts in globular proteins such that the X-ray crystal structure has a lower function value than that of thousands of protein-like alternative conformations. Although we fit the adjustable parameters of the potential using only 10,000 alternative structures for a selected training set of 37 proteins, a grand total of 530,000 constraints was satisfied, derived from 73 proteins and their numerous alternative conformations. In every case where the native conformation is adequately globular and compact, according to objective criteria we have developed, the potential function always favors the native over all alternatives by a substantial margin. This is true even for an additional three proteins never used in any way in the fitting procedure. Conformations differing only slightly from the native, such as those coming from crystal structures of the same protein complexed with different ligands or from crystal structures of point mutants, have function values very similar to the native's and always less than those of alternatives derived from substantially different crystal structures. This holds for all 95 structures that are homologous to one or another of various proteins we used. Realizing that this potential should be useful for modeling the conformation of new protein sequences from the body of protein crystal structures, we suggest a test for deciding whether a nearly correct approximation to the native conformation has been found. PMID- 1404393 TI - Analysis of the heat capacity dependence of protein folding. AB - This paper presents an analysis of plots of enthalpy versus heat capacity change at 25 degrees C for the unfolding of proteins and for the dissolution of gaseous, liquid and solid solutes, first reported by Murphy, Privalov & Gill. The negative slope in the enthalpy plot for proteins is interpreted as arising from a large penalty associated with burying polar groups in the protein interior. The small enthalpy changes that accompany protein unfolding at 25 degrees C are also discussed. It is argued that the combined effects of hydrogen bond formation and close packing predict a large positive enthalpy of unfolding. Electrostatic calculations indicate that the penalty associated with burying polar groups is large enough to effectively cancel these terms, leading to the small net enthalpy changes that are observed. The free energy changes associated with protein folding are also discussed. The free energy cost of burying polar groups largely compensates for the stabilizing contribution of the hydrophobic effect and would appear to account for the fact that proteins are marginally stable, independent of their size and of their relative hydrophobicities. PMID- 1404394 TI - Structure of a hinge-bending bacteriophage T4 lysozyme mutant, Ile3-->Pro. AB - The mutant T4 phage lysozyme in which isoleucine 3 is replaced by proline (I3P) crystallizes in an orthorhombic form with two independent molecules in the asymmetric unit. Relative to wild-type lysozyme, which crystallizes in a trigonal form, the two I3P molecules undergo large hinge-bending displacements with the alignments of the amino-terminal and carboxy-terminal domains changed by 28.9 degrees and 32.9 degrees, respectively. The introduction of the mutation, together with the hinge-bending displacement, is associated with repacking of the side-chains of Phe4, Phe67 and Phe104. These aromatic residues are clustered close to the site of the mutation and are at the junction between the amino and carboxyl-terminal domains. As a result of this structural rearrangement the side chain of Phe4 moves from a relatively solvent-exposed conformation to one that is largely buried. Mutant I3P also crystallizes in the same trigonal form as wild type and, in this case, the observed structural changes are restricted to the immediate vicinity of the replacement. The main change is a shift of 0.3 to 0.5 A in the backbone of residues 1 to 5. The ability to crystallize I3P under similar conditions but in substantially different conformations suggests that the molecule undergoes large-scale hinge-bending displacements in solution. It is also likely that these conformational excursions are associated with repacking at the junction of the N-terminal and C-terminal domains. On the other hand, the analysis is complicated by possible effects of crystal packing. The different I3P crystal structures show substantial differences in the binding of solvent, both at the site of the Ile3-->Pro replacement and at other internal sites. PMID- 1404395 TI - Preliminary crystallographic studies of urease from jack bean and from Klebsiella aerogenes. AB - Ureases from both jack bean (Canavalia ensiformis) seeds and Klebsiella aerogenes have been crystallized by the hanging drop method. The plant-derived urease crystals are regular octahedra analogous to those obtained by Sumner. Preliminary X-ray diffraction studies show that the crystals belong to the cubic space group F4(1)32, with a = 364 A, and appear to contain one or two subunits in the asymmetric unit. Using a synchrotron source, the crystals diffract to near 3.5 A resolution. Crystals of urease from K. aerogenes belong to the cubic space group I23 or I2(1)3, with a = 170.8 A and appear to contain a single catalytic unit per asymmetric unit. The crystals diffract to better than 2.0 A resolution and are well suited for structural analysis. PMID- 1404396 TI - Crystallization and preliminary X-ray diffraction study of Lathyrus ochrus isolectin II complexed to the human lactotransferrin N2 fragment. AB - Isolectin II (LOL II) isolated from the seeds of Lathyrus ochrus has been crystallized in the presence of the N2 fragment (18,500 Da) isolated from human lactotransferrin, which contains an N-acetyllactosamine type biantennary glycan linked to Asn137. This is the first example of a legume lectin crystallized with an N-glycosylprotein. Crystals of the LOL II-N2 complex belong to the tetragonal space group (P4(1)2(1)2 or the enantiomorph) with cell dimensions: a = b = 63.5 A, c = 251.9 A. They diffract well up to at least 3.5 A resolution and more weakly up to 2.8 A resolution. Assuming one functional half-entity in the asymmetric unit, an alpha, beta monomer complexed to one N2 fragment (24,500 Da + 18,500 Da) would give a Vm of 2.95 A3/Da and a solvent content of approximately 58%. SDS/polyacrylamide gels of the dissolved crystals show the presence of both the LOL II and N2 fragment. PMID- 1404397 TI - Crystallization and preliminary X-ray study of the cathepsin B complexed with CA074, a selective inhibitor. AB - Cathepsin B from bovine spleen has been purified and crystallized as a complex with a specific inhibitor CA074 [N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl) L- isoleucyl-L-proline], using the hanging-drop method. The complex crystals obtained from 50 mM-citrate buffer (pH 3.5) belong to the tetragonal space group P4(1) (or P4(3)) with a = 73.06 A and c = 141.59 A, and diffract beyond 2.2 A resolution. There are two complex molecules per asymmetric unit giving a packing density of 3.37 A3/Da and indicating a high solvent content of 63.5%. PMID- 1404398 TI - Crystallization and X-ray examination of bovine adrenodoxin. AB - Crystals of adrenodoxin from bovine adrenocortical mitochondria were obtained by the hanging-drop vapor diffusion technique. The crystals belong to a hexagonal crystal lattice with cell parameters 172.50 A and 183.49 A. There are 12 molecules in the asymmetric unit. The crystals diffract to beyond 4.0 A resolution. PMID- 1404399 TI - Amino acid sequence of yeast hemoglobin. A two-domain structure. AB - The complete amino acid sequence of a hemoglobin from yeast (Candida norvegensis) has been determined by peptide and cDNA sequence analyses. The protein is composed of 387 amino acid residues and its amino terminus was blocked by an acetyl group. A computer search showed that the sequence of 155 N-terminal residues has 39% homology with that of Vitreoscilla hemoglobin. On the other hand, the sequence of 230 C-terminal residues showed a small, but notable, degree of similarity with that of a methemoglobin reductase found in human erythrocyte, i.e. NADH-cytochrome b5 oxido-reductase. We therefore conclude that yeast hemoglobin consists of two distinct domains; one is a heme-containing oxygen binding domain of the N-terminal region and the other is an FAD-containing reductase domain found in the C-terminal region. PMID- 1404400 TI - Tunicate muscle actin genes. Structure and organization as a gene cluster. AB - We have isolated and determined the complete nucleotide sequences of two genes, HrMA4a and HrMA2, which encode the same muscle actin protein of the tunicate Halocynthia roretzi. HrMA4a and HrMA2 contain three exons, and the genes have intron-exon splice junctions at the same positions. The 5' flanking region of HrMA4a gene contains several potential regulatory elements. A TATA box is located at -30 and a CArG box found in regulatory region of vertebrate muscle-specific genes is located at -116. Seven E-box consensus sequences (CANNTG) known as binding sites for vertebrate myogenic determination factors are found within a 500 base-pair portion of the 5' flanking region of HrMA4a gene. HrMA4a and HrMA2 are separated by 1600 bases in genomic DNA and transcribed in the same direction. In addition to these genes, we have identified three other actin genes encoding muscle-type actins. All five actin genes are located in a 30 x 10(3) base-pair region of the genome and aligned in the same direction. This is the first report of a cluster of "vertebrate-type" muscle actin genes. The consensus sequences of 5' flanking region are conserved among these five genes, suggesting that the expression of the genes is controlled coordinately. This may be advantageous for the accumulation of considerable amounts of actin proteins in rapidly developing embryos of this animal. PMID- 1404401 TI - Large ATP synthase operon of the red alga Antithamnion sp. resembles the corresponding operon in cyanobacteria. AB - The large plastid ATP synthase operon of the multicellular red alga Antithamnion sp. was cloned and the sequence of six ATPase genes determined. The operon resembles more the one from cyanobacteria than the ATP synthase operon of the chloroplast genome. The gene order is atpI, H, G, F, D and A, coding for the ATPase subunits a, c, b', b, delta and alpha, respectively. In green plants, the genes atpG and atpD are located in the nucleus. Unlike the situation in three published cyanobacterial ATP synthase operons, atpC, coding for the gamma subunit, is not a part of the rhodoplast operon. A single 4.5 kb transcript was detected with atpG, F, D and A gene probes that could span the whole operon, but no transcript could be detected with atpI and atpH probes. The end of an open reading frame preceding the atp genes shows remarkable homology to elongation factor TS from Escherichia coli. Behind the ATPase cluster, two open reading frames were detected that are not homologous to any known chloroplast gene. One of them may code for a transport protein of unknown specificity. Gene arrangement and sequence comparisons support the hypothesis of a polyphyletic origin of rhodoplasts and chloroplasts. PMID- 1404402 TI - Ultrastructural qualitative and quantitative data on the sporogenesis of the protozoan Abelspora portucalensis (Microspora, Abelsporidae): a different approach to the study of microsporidia. AB - The sporogenesis of the microsporidium Abelspora portucalensis was studied with electron microscopy. In qualitative terms, new aspects of the cytoplasmic ultrastructure of the schizont, sporont, and sporoblast are described: the presence of microtubules, of aggregates of small opaque vesicles, and of dispersed larger vesicles with clear matrix. The hypothesis that the opaque vesicles may represent the Golgi apparatus and the clear vesicles may correspond to the smooth endoplasmic reticulum is discussed. The use of standard stereological and statistical techniques gives us a new perspective on the development of this microsporidium. The most relevant quantitative data display that the amount of rough endoplasmic reticulum (either in relative or absolute terms) presents significant differences among the three stages, with the sporont showing the highest values; that the absolute (but not the relative) volume of the large vesicles significantly changes during sporogenesis with the highest values presented by the sporont; that the surface-to-volume ratio of the schizont and sporont cells is similar and significantly greater than that of the sporoblast cell; that the surface density of the nucleus in relation to soma remains constant in the three stages (on the contrary, the surface-to-volume ratio of the nucleus increases and its volumetric density diminishes); and finally, that the nucleolus decreases its relative and absolute volumes. The functional significance of these results is analyzed and the application of similar methodology in quantifying the effects of drugs upon microsporidia is suggested. PMID- 1404403 TI - Visual demonstration of the limb-forming zone in the chick embryo lateral plate. AB - The present study was undertaken to determine whether a visible Wolffian ridge, distinct from the lateral fold, can be identified in chick embryos. Ectoderm thickness was measured in stage 11-17 chick embryos. There was a general trend, from thin ectoderm in the midline, to an ectodermal thickening over the somites, intermediate mesoderm, and lateral plate. Other embryos were cut from the yolk, pinned out, and photographed. The lateral fold was then eliminated, and the embryo was rephotographed. The photographs reveal a definite opaic zone, distinct from the lateral fold, in stage 11-18 chick embryos. Furthermore, there is a direct correlation between the opacity of this cellular band and the limb-forming potential of grafted wing, flank, and leg regions (see Stephens et al., '89). At stages 11-14, the wing, flank, and leg exhibit a uniform opacity, and a uniform capacity for limb formation when grafted to a host celom. From stage 15 to stage 18, the opacity in the flank diminishes, and its limb-forming capability disappears. This study demonstrates the presence of an opaic zone, which we have called the limb-forming zone (LFZ) along the lateral side of early chick embryos, which is independent of the lateral fold, is not as extensive as the lateral plate, and is not simply associated with ectodermal thickening, but which is directly correlated with limb-forming potential in the lateral plate. PMID- 1404404 TI - Vertebral development of the chick embryo during days 3-19 of incubation. AB - Chick embryo vertebral development has been studied during the period from 3 to 19 days of incubation. Whole mount preparations stained with alcian blue for cartilage and alizarin red for bone show the vertebral bodies as cartilaginous at 5 days, with dorsal spinous processes at 6 1/2 days, the onset of bone formation at the ventral and dorsal surfaces of the bodies at 13 days, ossification extending dorsally within the neural arches at 13 1/2 days, and bone development occurring throughout the vertebrae at 16 days. Descriptions at each time period center on the thoracic vertebrae with occasional inclusion of adjacent lower cervical and upper lumbar vertebrae. Histologic development is correlated with the Hamburger-Hamilton stages, which are based on external characteristics. The notochord and neural tube are well developed by 3 days and surrounded by sclerotome, myotome, and dermatome cells. Cartilage formation in the perinotochordal region of the vertebral body is seen at 5 days and precedes development of the neural arches and spinous processes. Separate centers of chondrocyte hypertrophy occur in the body (9 days), the lateral neural arches and the dorsal spinous process. Bone formation is under way at 13 days, beginning in the vertebral bodies. Intramembranous periosteal bone formation is seen adjacent to internal regions of chondrocyte hypertrophy. Vascular invasion of hypertrophic chondrocyte regions occurs, but the mechanism of endochondral ossification differs from that of mammals. The cartilage is resorbed by multinucleated chondroclasts and marrow round cells. Clumps of growth plate cartilage cells and matrix are surrounded occasionally by newly synthesized bone, but invasion of individual hypertrophic chondrocyte lacunae by vessels with bone deposition by accompanying osteoblasts on single trabeculae of cartilage does not occur. 3H thymidine autoradiography shows high uptake at 3 and 5 days in the germinal neuroepithelial cells of the neural tube (spinal cord) and notochord. By 7 days, notochordal uptake is markedly diminished, and no uptake of isotope occurs from 8 days onward. Spinal cord uptake is highest in the first 8 days but persists in lessened amounts to 19 days. From 5 days onward, both undifferentiated mesenchymal cells and differentiated chondrocytes show positive 3H-thymidine uptake, but labeling is never seen in hypertrophic chondrocytes. PMID- 1404405 TI - Glomerular development and growth of the renal blood vascular system in Xenopus laevis (Amphibia: Anura: Pipidae) during metamorphic climax. AB - Microcorrosion casts of the renal vascular system of tadpoles of the Clawed Frog, Xenopus laevis, were observed by scanning electron microscopy. Glomerular differentiation was studied qualitatively and quantitatively during developmental stages 56-66 (metamorphic climax). The general structure of the renal vascular system corresponds to the pattern commonly found in anurans; however, the arterial supply has conspicuous connecting vessels that supply groups of glomeruli. In the dorsal part of the kidney, qualitative differentiation of glomerular structures precedes quantitative growth. The ventral part of the kidney has larger, well-developed renal corpuscles of nearly adult appearance. Four developmental stages of glomerulogenesis are distinguished morphologically and their glomerular and vascular growth is analyzed. PMID- 1404406 TI - Anatomy of synganglia, including their neurosecretory regions, in unfed, virgin female Ixodes scapularis say (Acari: Ixodidae). AB - The central nervous system of Ixodes scapularis is fused into a single compact synganglion. The esophagus runs through the synganglion and divides it into supraesophageal and subesophageal parts. The supraesophageal portion contains a single protocerebrum with four pairs of glomeruli, paired optic lobes and cheliceral ganglia, and a single stomodeal bridge. The subesophageal portion contains a centrally located network of commissures and connectives, a pair of palpal ganglia, paired olfactory lobes of the first pedal ganglia, four pairs of pedal ganglia, and a single opisthosomal ganglion. A retrocerebral organ complex (ROC) in close vicinity of the digestive tract, as described in some other tick species, apparently is lacking. Perhaps the function of the ROC is performed by the paired, large, ganglion-like bodies that lie anterolaterad to the cheliceral ganglia. The rind, which is formed from the neuronal somata and glial cells, surrounds the central fibrous core or neuropile. Neurosecretory cells (NSC) are distinct among rind cells due to their large size and concentration of cytoplasmic neurosecretions. NSC are present throughout the synganglion, although the subesophageal portion contains larger groups of these cells. Histological serial sections, stained with Meola's (Trans Am Microsc Soc 89:66-71, '70) paraldehyde fuchsin (PAF) procedure revealed 24 PAF-stained, putative neurosecretory regions in the synganglion of virgin, unfed females. All of these regions appear to be connected and associated with the nearest ganglion and are correspondingly named. Eighteen PAF-positive regions occur in the synganglion. In addition, PAF-negative (green-stained) cells occupy 6 distinct regions in the synganglion of unfed, unmated females. PMID- 1404407 TI - Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man. AB - The ultrastructural quantitative composition of normal myocardial cells has been studied in 10 different species: man, dog, pig, cat, rabbit, ferret, guinea-pig, rat, mouse, and bat. Volume densities of mitochondria, myofibrils, and cytoplasm were determined using morphometry. It was found that the content of mitochondria differs in various species ranging between 22.0-37.0%. It is a very specific and constant value for any particular species, the smallest having the highest content. A close correlation exists between the mitochondrial volume density, heart rate and the rate of basal oxygen consumption in any group of animals. The myofibrillar volume density shows no species variability. It was about 60.0% in all species. It is concluded that the mitochondrial volume density is a good indicator of the oxidative capacity of cardiac muscle and that the species specific normal ultrastructural myocyte composition should be a useful baseline in pathophysiological studies of the heart in various animals. PMID- 1404408 TI - Guanosine metabolism in adult rat cardiac myocytes: inhibition by acyclovir and analysis of a metabolic pathway. AB - The metabolic fate of transported guanosine was examined in adult rat cardiac myocytes. Freshly isolated cells were incubated with 50 microM 8-[3H]-guanosine and the purine nucleoside phosphorylase (PNP) inhibitor acyclovir, and the nucleotide products extracted and examined for radiolabel distribution. Acyclovir inhibited guanosine incorporation into the 5'-nucleotide pool up to 66%. The drug did not inhibit guanosine transport. Other experiments using 5'-[3H]-guanosine and 8-[14C]-guanosine in concert as metabolic tracers showed both tritium and radiocarbon in the guanine nucleotide products. We concluded from this study that both a kinase (probably adenosine kinase) and the enzyme pair purine nucleoside phosphorylase/hypoxanthine-guanine phosphoribosyltransferase are responsible for guanosine salvage in heart cells. PMID- 1404409 TI - Growth properties and biochemical characterization of collagens synthesized by adult rat heart fibroblasts in culture. AB - Collagen is the most important component of the extracellular matrix of the myocardium; it supports the myocytes and maintains the architecture of the heart. Collagen also participates in the myocardial response to various forms of pressure overload. Increased tissue collagen content occurs as a result of spontaneous or experimental overload-induced myocardial hypertrophy. In order to determine the mechanisms responsible for the increased collagen deposition in experimental cardiac hypertrophy, we established monolayer cultures of fibroblasts isolated from normal adult rat myocardium and studied their growth and biosynthetic characteristics. These cells have a doubling time of about 20h and synthesize and secrete several collagenous and non-collagenous proteins. We found that type I collagen was the major collagenous product of these cells representing 80% of total newly synthesized collagen. Most of the newly synthesized collagen was secreted into the culture medium as intact and partially cleaved procollagens. About 20% of the total collagen synthesized was type III collagen which was also secreted into the medium as a procollagen. A small proportion of type V collagen (less than 5%) was also synthesized by these cultures. Fibronectin which was identified by its mobility in SDS gel electrophoresis was quantified by immunoprecipitation with specific antisera and was the most abundant non-collagenous protein synthesized by these cells. Northern blot hybridization analysis demonstrated that these cells expressed transcripts for alpha 1 chains of types I and III collagen and for fibronectin. PMID- 1404410 TI - Ischemic but not reperfusion arrhythmias depend upon serum potassium concentration. AB - The effects of variations in serum concentrations of potassium on the occurrence and severity of ischemia- and reperfusion-induced arrhythmias have been studied in conscious rats. Serum potassium concentrations were modified by maintaining rats on diets which varied in potassium concentration, by treatment with hydrochlorothiazide, amiloride, spironolactone or infusions of potassium chloride. An inverse linear relationship was demonstrated between ischemia induced arrhythmias and log(e) serum potassium concentration such that a 50% reduction in arrhythmias occur with a 3.8-fold increase in serum potassium concentration. On the other hand, the incidence of reperfusion-induced arrhythmias after 7 min of regional ischemia prior to reperfusion in previously untreated rats were not influenced by elevation of serum potassium concentrations prior to and after reperfusion. Effects on ischemia-induced arrhythmias could not be explained by changes in blood pressure or heart rate. It is speculated that modification of potassium concentration in non-ischemic or border zone ventricular tissue may directly modify arrhythmogenesis due to ischemia but not that due to reperfusion. PMID- 1404411 TI - Myocardial myoglobin deficiency in various animal models of congestive heart failure. AB - Myoglobin is known to protect the mechanical function of the heart from hypoxia by acting as a sarcoplasmic oxygen reservoir and shuttle. We postulated a role for myoglobin in the pathogenesis of congestive heart failure. Several models of congestive heart failure were employed to test the hypothesis, including spontaneous inherited dilated cardiomyopathy in Doberman Pinschers, and heart failure produced by rapid ventricular pacing in dogs, volume overload in chickens and furazolidone toxicity in turkeys. Myocardial myoglobin was decreased by approximately 50% for all models (P less than 0.05). In Doberman Pinschers dogs which are predisposed to the development of dilated cardiomyopathy and have mild subclinical depression of cardiac performance, myocardial myoglobin (1.05 +/- 0.22 mg/g) is approximately 50% decreased compared to healthy mongrel dogs (2.15 +/- 0.52 mg/g), approximately twice as much as dobermans with heart failure (0.47 +/- 0.25 mg/g) but similar to the concentration found in dogs paced to heart failure (1.09 +/- 0.34 mg/g). Myocardium from poultry had remarkably decreased myoglobin compared to mammals (34 +/- 4 micrograms/g) with heart failure produced either by furazolidone or salt toxicity causing a further 50% reduction. In the canine models of heart failure, myocardial myoglobin concentration was demonstrated to be correlated with biochemical and physiological indicators of myocardial performance, namely, mitochondrial and sarcoplasmic reticular ATPase activities, and cardiac output, systemic vascular resistance, pulmonary capillary wedge pressure and mean arterial pressure, respectively. Our data implicates a role for myoglobin deficiency in the pathogenesis of congestive heart failure and in the predisposition of doberman pinschers to dilated cardiomyopathy. PMID- 1404412 TI - Paradoxical effect of cerium on collagen synthesis in cardiac fibroblasts. AB - The present study examined the effect of cerium on collagen synthesis in cultured cardiac fibroblasts and explants. At 100 nM, a concentration comparable with that found in the cardiac tissue of patients with endomyocardial fibrosis, the element was found to enhance the incorporation of tritiated proline into collagen and non collagen proteins while at 10 microM, it had an inhibitory effect. Cerium was found to have no effect on rates of DNA synthesis in fibroblasts at 100 nM. However, at this concentration, the element markedly enhanced the incorporation of tritiated uridine into RNA, suggesting that cerium may act at the level of transcription to stimulate collagen and non-collagen protein syntheses. The stimulatory action of very low levels of cerium on collagen synthesis may contribute to the accumulation of collagen seen in endomyocardial fibrosis. PMID- 1404413 TI - Program and abstracts of the XIIIth European Section Meeting of the International Society for Heart Research (From Basics to Clinics). Heidelberg, Germany, 1-3 October 1992. PMID- 1404414 TI - Prototypic sequences for human repetitive DNA. AB - We report a collection of 53 prototypic sequences representing known families of repetitive elements from the human genome. The prototypic sequences are either consensus sequences or selected examples of repetitive sequences. The collection includes: prototypes for high and medium reiteration frequency interspersed repeats, long terminal repeats of endogenous retroviruses, alphoid repeats, telomere-associated repeats, and some miscellaneous repeats. The collection is annotated and available electronically. PMID- 1404415 TI - Relative rates of nucleotide substitution at the rbcL locus of monocotyledonous plants. AB - We subjected 35 rbcL nucleotide sequences from monocotyledonous taxa to maximum likelihood relative rate tests and estimated relative differences in rates of nucleotide substitution between groups of sequences without relying on knowledge of divergence times between taxa. Rate tests revealed that there is a hierarchy of substitution rate at the rbcL locus within the monocots. Among the taxa analyzed the grasses have the most rapid substitution rate; they are followed in rate by the Orchidales, the Liliales, the Bromeliales, and the Arecales. The overall substitution rate for the rbcL locus of grasses is over 5 times the substitution rate in the rbcL of the palms. The substitution rate at the third codon positions in the rbcL of the grasses is over 8 times the third position rate in the palms. The pattern of rate variation is consistent with the generation-time-effect hypothesis. Heterogenous rates of substitution have important implications for phylogenetic reconstruction. PMID- 1404416 TI - Rapid evolution of the plastid translational apparatus in a nonphotosynthetic plant: loss or accelerated sequence evolution of tRNA and ribosomal protein genes. AB - The vestigial plastid genome of Epifagus virginiana (beechdrops), a nonphotosynthetic parasitic flowering plant, is functional but lacks six ribosomal protein and 13 tRNA genes found in the chloroplast DNAs of photosynthetic flowering plants. Import of nuclear gene products is hypothesized to compensate for many of these losses. Codon usage and amino acid usage patterns in Epifagus plastic genes have not been affected by the tRNA gene losses, though a small shift in the base composition of the whole genome (toward A+T-richness) is apparent. The ribosomal protein and tRNA genes that remain have had a high rate of molecular evolution, perhaps due to relaxation of constraints on the translational apparatus. Despite the compactness and extensive gene loss, one translational gene (infA, encoding initiation factor 1) that is a pseudogene in tobacco has been maintained intact in Epifagus. PMID- 1404417 TI - The nucleotide sequence of the entire ribosomal DNA operon and the structure of the large subunit rRNA of Giardia muris. AB - The total nucleotide sequence of the rDNA of Giardia muris, an intestinal protozoan parasite of rodents, has been determined. The repeat unit is 7668 basepairs (bp) in size and consists of a spacer of 3314 bp, a small-subunit rRNA (SSU-rRNA) gene of 1429, and a large-subunit rRNA (LSU-rRNA) gene of 2698 bp. The spacer contains long direct repeats and is heterogeneous in size. The LSU-rRNA of G. muris was compared to that of the human intestinal parasite Giardia duodenalis, to the bird parasite Giardia ardeae, and to that of Escherichia coli. The LSU-rRNA has a size comparable to the 23S rRNA of E. coli but shows structural features typical for eukaryotes. Some variable regions are typically small and account for the overall smaller size of this rRNA. The structure of the G. muris LSU-rRNA is similar to that of the other Giardia rRNA, but each rRNA has characteristic features residing in a number of variable regions. PMID- 1404418 TI - Six strains of human immunodeficiency virus type 1 isolated in Japan and their molecular phylogeny. AB - Five strains of human immunodeficiency virus type 1 (HIV-1) were isolated from five Japanese hemophilia patients. Two isolates, HIV-1[GUN-1] and HIV-1[GUN-2], were from brother patients with hemophilia B and the other three isolates, HIV 1[GUN-3], HIV-1[GUN-4], and HIV-1[GUN-5], were from hemophilia A patients. Another HIV-1 strain, HIV-1[GUN-6], was isolated from a Canadian male homosexual with AIDS. The restriction endonuclease cleavage maps of the proviral genomes of these six HIV-1 strains revealed that they were apparently different from each other. The phylogenetic trees constructed using restriction maps and nucleotide sequences were quite similar, indicating that phylogenetic analyses of Japanese HIV-1 isolates can be done using restriction maps of the proviruses. Phylogenetic analyses showed that they were more closely related to HIV-1s which had been reported to be isolated from homosexual patients in the United States than those isolated from African patients. In particular, GUN-1 and GUN-2 isolates were on the branch of a San Francisco isolate, ARV2, while GUN-5 and GUN-6 isolates were on the branch of HTLV-IIIB-related isolates. PMID- 1404420 TI - Radionuclide-induced evolution of DNA and the origin of life. AB - Artesian groundwaters of high radionuclide concentration are ubiquitous and may have provided the large, sustained energy sources that were required to drive the multistage process of DNA and primordial cell evolution. The rapid, early development of the genetic code as well as its degeneracy can be attributed to exceptionally high radiation-induced mutation rates in this unique environment. The ability of double-strand DNA to direct enzymatic repair of radiation damage to single strands contributed importantly to its selective evolution. It is postulated that the polymerization of nucleotides took place at elevated temperatures within alpha-particle tracks of high ion and free-radical density, followed by rapid quenching to ambient conditions. It also is evident that radiation resistance and ploidy were important selection factors in cellular evolution. PMID- 1404419 TI - Conservation of mouse alpha A-crystallin promoter activity in chicken lens epithelial cells. AB - Previous transfection experiments have shown that 162 base pairs (bp) of the 5' flanking sequence of the chicken alpha A-crystallin gene are required for promoter activity in primary chicken lens epithelial cells (PLE), while only 111 bp of the 5' flanking sequence are needed for activity of the mouse alpha A crystallin promoter in transfected chicken PLE cells or in a SV40 T-antigen transformed transfected mouse lens epithelial cell line (alpha TN4-1). The effect of site-directed mutations covering positions -111 to -34 of the mouse alpha A crystallin promoter fused to the bacterial chloramphenicol acetyltransferase (CAT) gene was compared in transfected chicken PLE cells and mouse alpha TN4-1 cells; selected mutations were also examined in a nontransformed rabbit lens epithelial cell line (N/N1003A). In general, the same mutations reduced promoter activity in the transfected lens cells from all three species, although differences were noted. The mutations severely affected regions -111/-106 and 69/-40 regions in all the transfected cells examined; by contrast, mutations at positions -105/-99 and -87/-70 had a somewhat greater effect in the chicken PLE than the mouse alpha TN4-1 cells, while mutations of the -93/-88 sequence reduced expression in the alpha TN4-1 but not the PLE cells. A partial cDNA with sequence similarity to alpha A-CRYPB1 of the mouse has been isolated from a chicken lens library; mouse alpha A-CRYBP1 is a putative transcription factor which binds to the -66/-55 sequence of the mouse alpha A-crystallin promoter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404422 TI - Statistical properties of the ordinary least-squares, generalized least-squares, and minimum-evolution methods of phylogenetic inference. AB - Statistical properties of the ordinary least-squares (OLS), generalized least squares (GLS), and minimum-evolution (ME) methods of phylogenetic inference were studied by considering the case of four DNA sequences. Analytical study has shown that all three methods are statistically consistent in the sense that as the number of nucleotides examined (m) increases they tend to choose the true tree as long as the evolutionary distances used are unbiased. When evolutionary distances (dij's) are large and sequences under study are not very long, however, the OLS criterion is often biased and may choose an incorrect tree more often than expected under random choice. It is also shown that the variance-covariance matrix of dij's becomes singular as dij's approach zero and thus the GLS may not be applicable when dij's are small. The ME method suffers from neither of these problems, and the ME criterion is statistically unbiased. Computer simulation has shown that the ME method is more efficient in obtaining the true tree than the OLS and GLS methods and that the OLS is more efficient than the GLS when dij's are small, but otherwise the GLS is more efficient. PMID- 1404421 TI - Statistical properties of bootstrap estimation of phylogenetic variability from nucleotide sequences: II. Four taxa without a molecular clock. AB - The statistical properties of sample estimation and bootstrap estimation of phylogenetic variability from a sample of nucleotide sequences were studied by considering model trees of three taxa with an outgroup. The cases of constant and varying rates of nucleotide substitution were compared. From sequences obtained by simulation, phylogenetic trees were constructed by using the maximum parsimony (MP) and neighbor-joining (NJ) methods. The effectiveness and consistency of the MP method were studied in terms of proportions of informative sites. The results of simulation showed that bootstrap estimation of the confidence level for an inferred phylogeny can be used even under unequal rates of evolution if the rate differences are not large so that the MP method is not misleading. The condition under which the MP method becomes misleading (inconsistent) is more stringent for slowly evolving sequences than for rapidly evolving ones, and it also depends on the length of the internal branch. If the rate differences are large so that the MP method becomes consistently misleading, then bootstrap estimation will reinforce an erroneous conclusion on topology. Similar conclusions apply to the NJ method with uncorrected distances. The NJ method with corrected distances performs poorly when the sequence length is short but can avoid the inconsistency problem if the sequence length is long and if the distances can be estimated accurately. PMID- 1404423 TI - Fetal cortical cells survive in focal cerebral infarct after permanent occlusion of the middle cerebral artery in adult rats. AB - Fetal rat cortical cells have been shown previously to survive at the periphery of cerebral infarction. The present study was designed to examine the ability of fetal cells to survive at the edge of the central core of ischemia. In three groups of 8 adult Sprague-Dawley rats, fetal cortical cells from ED 16 were stereotactically transplanted at 3 h, 24 h, and 7 days after unilateral middle cerebral artery occlusion. In 6 rats, fetal cells were transplanted by using the same coordinates, without arterial occlusion, for control. In the ischemic groups, overall graft survival was 85%, and in the control group, all grafts survived. Graft survival was determined by light microscopy. No significant difference was found in the survival of grafts transplanted at different intervals after middle cerebral artery occlusion. It is concluded that fetal cortical cells can survive in cerebral tissue undergoing severe ischemic change. PMID- 1404424 TI - In vitro models of mechanical injury. PMID- 1404425 TI - A monitored contusion model of spinal cord injury in the rat. PMID- 1404427 TI - Comment: modeling for drug development in spinal cord injury. PMID- 1404426 TI - Experimental spinal cord injury: a dynamic and verifiable injury device. PMID- 1404428 TI - Hemodynamic issues and vascular factors in acute experimental spinal cord injury. PMID- 1404429 TI - Chemical and cellular mediators in spinal cord injury. PMID- 1404430 TI - Spinal cord injury models: neurophysiology. PMID- 1404431 TI - Rapid quantification of tissue damage for assessing acute spinal cord injury therapy. PMID- 1404432 TI - Anatomic and behavioral outcome after spinal cord injury produced by a displacement controlled impact device. PMID- 1404433 TI - Problematic issues in spinal cord injury. PMID- 1404434 TI - Behavioral endpoint measures for preclinical trials using experimental models of spinal cord injury. PMID- 1404435 TI - Comment: need for standardization of animal models of spinal cord injury. PMID- 1404436 TI - Importance of pharmacologic considerations in the evaluation of new treatments for acute spinal cord injury. PMID- 1404437 TI - Criteria for valid preclinical trials. PMID- 1404438 TI - Glucose hypermetabolism after acute subdural hematoma is ameliorated by a competitive NMDA antagonist. AB - Intracranial hematomas occur in almost half of patients who sustain a severe head injury, and outcome is particularly poor in patients with acute subdural hematoma. We have measured regional cerebral glucose metabolism (2-deoxyglucose autoradiography) in a new rat model of acute subdural hematoma and compared the changes to those seen in sham-operated control animals and animals pretreated with a high-affinity competitive NMDA antagonist, D-CPP-ene. At 2 h after inducing the hematoma, a severe reduction in glucose use was seen in the cortex beneath the hematoma (less than 5 mumol/100g/min) consistent with a zone of histologic infarction seen in other studies. A band of markedly increased glucose use was seen in the periischemic zone, surrounding this infarcted tissue and throughout the hippocampus bilaterally (up to 142% increase). Both the zone of reduced glucose use and the volume of tissue with increased glucose metabolism were significantly reduced in the animals pretreated with D-CPP-ene. These data indicate that the neuroprotective effect of NMDA antagonists, seen in this and other models, may be mediated by reducing the increased metabolism that occurs probably due to glutamate release. PMID- 1404440 TI - Marital therapy formats: an analysis of acceptability ratings with married spouses. AB - One hundred thirty-five married individuals evaluated the acceptability of alternative therapeutic formats commonly employed in marital therapy. Distressed and nondistressed spouses were randomly assigned to experimental conditions including two types of educational information (descriptive and group-oriented) presented across three treatment formats (i.e., individual, conjoint, and group). Primary dependent variables included the Treatment Evaluation Inventory and the Semantic Differential. Results revealed that conjoint format was most acceptable, followed by group and individual, respectively. However, distressed spouses rated the group and conjoint formats as equal in acceptability. Group-oriented information increased nondistressed subjects' ratings of group format. The implications of these results for clinicians and researchers offering marital therapy are discussed. PMID- 1404439 TI - Brain levels of polyethylene glycol-conjugated superoxide dismutase following fluid percussion brain injury in rats. AB - Polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) is being explored as an agent to reduce oxygen radical-mediated damage following brain injury. Yet little is known concerning the site of action of IV-administered PEG-SOD or the capacity of this conjugated enzyme to enter the brain. The purpose of this study was to determine the brain content of PEG-SOD in normal and fluid percussion injured rats. The fluid percussion device was attached over the right parietal cortex and a moderate (2.0 atm) intensity injury was produced. PEG-SOD was conjugated with 125I and given (2000 U/kg, 5 microCi/kg) to rats either 30 min before or 30 min after brain injury. Another group received [125I]PEG-SOD but was not injured. Plasma and left and right brain hemispheres were counted for [125I]PEG-SOD. Plasma levels of [125I]PEG-SOD declined similarly in all three groups during the 90-min period after IV administration. Brain [125I]PEG-SOD was low in control animals (0.034 U/g wet wt). In animals given PEG-SOD after injury the brain level was elevated sixfold in both the left and right hemispheres, compared to control. In rats given the drug before injury, [125I]PEG-SOD was 10 times control level in the right hemisphere, which is the side on which the injury device is attached, and 6 times control level in the left hemisphere. We conclude that traumatic brain injury produces an increase in brain PEG-SOD. The exact cellular site of the increased brain PEG-SOD remains to be clarified. PMID- 1404441 TI - A group therapy format for the simultaneous treatment of marital and sexual dysfunctions: a case illustration. AB - This report describes a brief, 15-session couples group therapy format developed by a university-affiliated human sexuality clinic for the simultaneous treatment of marital and sexual dysfunctions. The major marital and sexual themes addressed in this group treatment design, an overview and description of the structure of the cognitive-behavioral approach, and a case illustration are presented. PMID- 1404442 TI - Constructing a sex and marital therapy frame: ways to help couples deconstruct sexual problems. AB - It has been pointed out that an integration of the fields of marital and family therapy and sex therapy is needed. This paper proposes a model for the integration of sex therapy and marital therapy. Recently, social constructionism has made its way into the marital and family therapy literature. Using social constructionist notions, the present paper proposes an alternative perspective to the traditional sex therapy models--one that incorporates a constructionist therapeutic stance utilizing the notions of sexual meaning systems and sexual scripts. In so doing, an integrated model of sex and couple therapy is presented. PMID- 1404443 TI - Psychometric characteristics of individuals with sexual dysfunction and their partners. AB - This study assessed psychological dimensions and marital adjustment of 52 couples in which one of the partners met operational criteria for hypoactive sexual desire or erectile dysfunction. Information was obtained independently from the dysfunctional subjects and their partners by means of validated inventories: the Derogatis Sexual Function Inventory (DSFI), Locke-Wallace Marital Adjustment Test (L-W), and the Dyadic Adjustment Scale (DAS). The global measures of sexual function and satisfaction of the DSFI showed marked impairment in all groups, while its subscale scores suggested characteristic differences in the profiles of the dysfunctional groups and their partners. In contrast to individual psychologic measures, the assessment of marital adjustment was within the scale's normative limits in all diagnostic groups. There is a need for controlled studies to better characterize sexual and marital dimensions in diagnostically well defined dysfunctional couples. PMID- 1404444 TI - An empirical examination into the sexuality of women with borderline personality disorder. AB - In the last decade, a great deal of research has been accomplished in the study of borderline personality, but the literature is yet to systematically examine the intimate relationships of individuals with this particular personality disorder. In doing so, this study compared a sample of female borderlines with an adequately matched sample of non-personality disorders (aged 23-33 years) using the following measures: the Hurlbert Index of Sexual Assertiveness, the Sexual Opinion Survey, the Sexuality Scale, and the Index of Sexual Satisfaction. In the borderline sample, about 50% of the women reported a childhood history of physical or sexual abuse, as compared to about 15% in the control group. Also, borderline women were found to have significantly higher sexual assertiveness, greater erotophilic attitudes, and higher sexual esteem. Despite these findings, the borderline group evidenced significantly greater sexual preoccupation, sexual depression, and sexual dissatisfaction. Implications for these findings and treatment issues are discussed. PMID- 1404445 TI - Noninvasive treatment for erectile dysfunction in the neurogenically disabled population. AB - Erectile dysfunction is the most prevalent sexual dysfunction in neurogenically disabled men. Studies of rehabilitation patients indicate that the restoration of sexual functioning is considered an important priority. This article reports on a pilot study of vacuum tumescence constriction therapy as a noninvasive method for use by a population with traumatic or nontraumatic neurologic disorders such as spinal cord injury, stroke, multiple sclerosis, and diabetes mellitus. Of the 30 patients who participated in the study, 17 purchased the device and over 50% of them reported using the device on a long-term basis. Frequency of coitus increased from 0.3/wk to 1.5/wk. Included in the study are methods used by patients to integrate the device into their sex life, the role of the patient's partner in the decision to purchase the device, and the rate of partner satisfaction. There were no reports of substantial morbidity. Thus, this method shows promise as a noninvasive treatment for men who are moderately to severely neurogenically disabled. PMID- 1404446 TI - Case-control studies of colorectal cancer mortality: is the case made for screening sigmoidoscopy? PMID- 1404447 TI - Roswell Park: the phoenix rises in Buffalo. PMID- 1404448 TI - Breast cancer prevention study initiated in Italy. PMID- 1404449 TI - Reduction in plasma or skin alpha-tocopherol concentration with long-term oral administration of beta-carotene in humans and mice. AB - BACKGROUND: Beta-carotene is one of the most commonly used compounds in clinical trials of chemopreventive agents in various neoplastic diseases. Animal studies, including our own, have documented that dietary beta-carotene can reduce plasma alpha-tocopherol (vitamin E) levels, but few published studies have examined the clinical or pharmacokinetic ramifications of long-term, high-dose beta-carotene regimens on other fat-soluble vitamins such as alpha-tocopherol. PURPOSE: This study was designed to determine the effects of long-term beta-carotene supplementation on plasma concentrations of alpha-tocopherol in normal human subjects and in an experimental C3H/HeN mouse model. METHODS: In a double-blind study, 45 normal subjects were randomly assigned to receive 0 (placebo), 15, 30, 45, or 60 mg of oral beta-carotene daily for approximately 9 months. Monthly plasma samples were collected. Thirty-five C3H/HeN mice were fed a basal diet with or without beta-carotene and treated topically with or without alpha tocopherol, except for the control mice, which received UV radiation for 27 weeks from week 3 to week 30. Plasma and dorsal skin samples were taken after 40 weeks and were analyzed for alpha-tocopherol and/or beta-carotene by high-performance liquid chromatography. RESULTS: Long-term dietary beta-carotene administration resulted in statistically significant reductions in levels of alpha-tocopherol in the skin and plasma of UV-irradiated mice. In the human study, the decrease in plasma alpha-tocopherol levels was progressive and significant between 6 and 9 months of beta-carotene dosing in all dosage groups. The greatest decrease was observed during the 9th (last) month of dosing, with a decrease of 40% from baseline. All oral beta-carotene doses (15-60 mg/d), however, resulted in similar decreases in steady-state plasma levels of alpha-tocopherol and in only small differences in beta-carotene plasma levels. CONCLUSION: Long-term oral administration of beta-carotene decreased steady-state plasma concentrations of alpha-tocopherol. The lack of a significant dose-response effect between doses of beta-carotene and alpha-tocopherol plasma levels is not unexpected, given the small differences in steady-state beta-carotene plasma levels in the four beta carotene dose groups. IMPLICATIONS: Studies are needed to determine how long-term beta-carotene dosing influences tissue distribution of dietary alpha-tocopherol. Careful surveillance for this and other potentially harmful nutrient interactions should become part of all long-term intervention studies. PMID- 1404450 TI - Screening sigmoidoscopy and colorectal cancer mortality. AB - BACKGROUND: Sigmoidoscopy may reduce colorectal cancer mortality by identifying both cancers and precursor lesions (including polyps) for treatment; however, evidence regarding the efficacy of this technique as a screening procedure is extremely limited. PURPOSE: In the absence of data from randomized controlled trials, we performed a retrospective case-control study to determine if sigmoidoscopy screening is associated with a reduction in colorectal cancer mortality. METHODS: The medical records of 66 members of the Greater Marshfield Community Health Plan (GMCHP) who died of large-bowel cancer from 1979 to 1988 were reviewed for history of screening for colorectal cancer (case subjects). For comparison, the records of 196 GMCHP members of similar gender, age, and enrollment duration were randomly selected for review (control subjects). RESULTS: History of screening sigmoidoscopy was much less common among case subjects (10%) than among control subjects (30%). Risk for death from colorectal cancer was reduced among individuals having had a single examination by screening sigmoidoscopy (odds ratio = 0.21; 95% confidence interval = 0.08-0.52), compared with the risk for those who never had one. The reduction in risk appeared to be limited to tumors in the rectum and distal colon. Neither fecal occult blood testing nor digital rectal examination was associated with a reduction in colorectal cancer mortality. CONCLUSIONS: These results suggest that screening sigmoidoscopy can substantially reduce mortality from cancers of the rectum and distal colon. PMID- 1404451 TI - Breast cancer risk: effects of estrogen replacement therapy and body mass. AB - BACKGROUND: Epidemiologic studies have focused on the association between breast cancer risk and a variety of lifestyle and exogenous factors. PURPOSE: The purpose of this study was to clarify the effects of alcohol consumption, cigarette smoking, oral contraceptive (OC) use, estrogen replacement therapy (ERT), and body mass on risk of breast cancer. METHODS: These variables were examined in a case-control study of 604 patients with newly diagnosed breast cancer and 520 control subjects who did not have breast cancer and were frequency matched for age, hospital, and time of diagnosis. These case patients and control subjects were part of an ongoing study of breast cancer by the American Health Foundation and were selected for interview from hospitals in the New York City area from January 1987 through December 1989. The data were analyzed by computation of odds ratios (ORs) for potential risk factors, with adjustment for age at diagnosis and other potential confounding variables and with stratification by menopausal status. RESULTS: We observed positive effects of ERT and high body mass on the risk of postmenopausal breast cancer, particularly when each factor was examined in the absence of the other factor. In lean postmenopausal women, the adjusted summary OR associated with ERT was significantly elevated (OR = 2.0; 95% confidence interval [CI] = 1.1-3.5; P < .01), and there was a statistically significant dose response of breast cancer risk with ERT duration (adjusted ORs = 2.0 for < 5 years and 2.2 for > or = 5 years; positive trend, P < .02). Reciprocally, in women who did not receive ERT, high body mass (Quetelet index > 27) was a significant risk factor for postmenopausal breast cancer (OR = 2.1; 95% CI = 1.3-3.3; P < .02), and the linear trend in risk with increasing body mass was significant (positive trend, P < .02). The strongest effect of body mass occurred in women who were lean at age 18 and gained enough weight to place them in the upper tertile of body mass at the time of diagnosis (OR = 2.6; 95% CI = 1.5-4.6; P < .01). There was no evidence of significant positive associations between breast cancer risk and cigarette smoking, alcohol consumption, or OC use in any subgroup of these women. CONCLUSIONS: Our results support the hypothesis that excess adipose deposition heightens breast cancer risk in the postmenopausal years. Furthermore, they underscore the need for continuing investigation of the effects of exogenous estrogens on the development of this malignancy, particularly in lean postmenopausal women. PMID- 1404452 TI - Characterization of covalent DNA binding of morpholino and cyanomorpholino derivatives of doxorubicin. AB - BACKGROUND: The doxorubicin analogues cyanomorpholino doxorubicin (MRA-CN) and morpholino doxorubicin (MRA) were synthesized in an attempt to avoid the cardiotoxicity and drug resistance of doxorubicin therapy. MRA-CN forms interstrand DNA cross-links without requiring microsomal metabolic activation in the presence of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) to form a product that alkylates DNA, but MRA requires metabolic activation. Alkylation produces DNA cross-links, which are associated with potentiation of the cytotoxicity of some drugs. PURPOSE: Our purpose was to study the DNA binding of MRA-CN and MRA with and without metabolic activation in order to better understand the mechanisms for cross-linking DNA. METHODS: We used [3H]MRA and [3H]MRA-CN, with the 3H labeled at C-2 and C-6 of the morpholino ring. MRA (10 nM) was incubated with human liver microsomes with or without NADPH to measure DNA binding. In addition, a filter elution assay was used to determine the nature and extent of drug binding to DNA in the human ovarian carcinoma cell line ES-2. We studied the appearance of interstrand cross-links versus total DNA adducts in pBR322 plasmid DNA incubated with 100 nM MRA-CN in cell-free medium and then subjected to denaturation and agarose gel electrophoresis. RESULTS: Regardless of the extracellular concentration of the drug (1-100 nM), 85% of intracellular MRA CN was covalently bound to DNA, and the total amount of drug bound to DNA was proportional to extracellular drug concentration. No covalent binding of MRA to DNA was found in cells exposed to 10 nM MRA alone for 2 hours. In contrast, 10% of the intracellular drug was bound to DNA if the cells were exposed to MRA preincubated with human liver microsomes and NADPH. The percentage of plasmids containing at least one interstrand cross-link rose from 35% at 15 minutes to 92% at 2 hours. We estimate that eight molecules of MRA-CN were adducted per molecule of pBR322 DNA (or one drug adduct per 545 base pairs), with a minimum of 12% of the adducts forming interstrand cross-links. CONCLUSIONS: These results suggest that the carbons at positions 2 and 6 of the morpholino ring of both MRA-CN and the activated metabolite of MRA are retained in the drug-DNA adduct. They also indicate that the formation of interstrand DNA cross-links by MRA-CN is preceded by formation of drug adducts to a single strand of DNA. PMID- 1404453 TI - Non-acquired immune deficiency syndrome-defining malignancies in a hospital-based cohort of human immunodeficiency virus-infected patients: Bordeaux, France, 1985 1991. Groupe d'Epidemiologie Clinique du SIDA en Aquitaine. PMID- 1404454 TI - Case-control study of acute and nonlymphocytic leukemia. PMID- 1404455 TI - Long survival of patients with untreated gastric carcinoma. PMID- 1404456 TI - Partners in health-care reform. PMID- 1404457 TI - Explaining health disparities between African-American and white populations: where do we go from here? PMID- 1404458 TI - Violence as a public health priority for black Americans. AB - This study investigated the extent to which black public health and political leaders believe that reducing violence should be a national public health priority for black Americans when compared with other public health problems such as acquired immunodeficiency syndrome, low birthweight, and access to health care. A survey asking whether violence in the black community is amendable to change and who (or what institutions) should be responsible for the reduction of violence was sent to 427 black health leaders, 326 black mayors, and 467 black legislators. Three hundred twenty responses were returned. Virtually all respondents placed violence as one of the top five, if not the highest, public health priority for black Americans. Health and political leaders differed in their beliefs about whether violence and violence-related behaviors can be ameliorated, and who should bear responsibility for the reduction of violence. While this survey had limitations, more than 300 black public health and political leaders indicated that violence among black Americans should be made a national public health priority. Policy implications are discussed, and a proactive role for the National Medical Association is advocated. PMID- 1404459 TI - Appendicitis in children: a continuing clinical challenge. AB - This article discusses the findings of a study of pre-adolescent children to determine if the mode of presentation of appendicitis had changed over the past 10 years, if the incidence of perforations decreased with age, and if diagnosis related groups (DRGs) impacted the length of hospital stay. The charts of 42 children under the age of 12 years who were discharged from two inner-city hospitals with a diagnosis of acute appendicitis from 1980 to 1989 were reviewed. There were 20 blacks and 22 whites, 26 males and 16 females with an average age of 7.31 years (range: 2 to 11 years). Over 95% of patients presented with right lower quadrant pain, 78% with guarding, 80% with a positive psoas sign, 93% with a positive Rovsing's sign, and 65% with rectal tenderness. Over 85% of patients had a history of nausea, vomiting, and anorexia. The mean duration of pain was 52.8 hours and the mean temperature was 99.6 degrees F. The mean white blood cell count was 18,176 +/- 4682 for whites versus 14,615 +/- 5459 for blacks. At surgery 15/42 (36%) of patients had a perforation, 11 of whom had positive wound cultures. Escherichia coli was recovered in all 11 of these patients. The average duration of pain in the perforated group was 50.9 hours, and the average age was 7 years. Eleven of these patients had normal bowel sounds on admission. Only 31% of the total cohort had a fecalith identified by pathology. The average postoperative length of stay was 6.5 +/- 2.5 days before the initiation of DRGs and 7.5 +/- 3 days afterward. PMID- 1404460 TI - Change in serum cholinesterase activity in Jamaican diabetics. AB - This study investigates the alteration of serum cholinesterase levels in diabetics and its possible relationship to blood glucose, insulin, triglyceride, and cholesterol levels. Fourteen phasic insulin-dependent diabetes mellitus patients were compared with 10 insulin-dependent diabetes mellitus, 10 noninsulin dependent diabetes mellitus, and 10 normal controls. Each group was matched for age, sex, body mass index, and duration of diabetes. Mean age was 56.7 +/- 2.5 years; mean body mass index, 24.0 +/- 0.8 kg/m2; and mean duration of diabetes, 14.2 +/- 2.2 years. Serum acetylcholinesterase, insulin, triglyceride, and cholesterol levels as well as fasting blood sugar were all assayed using standard techniques. Results suggest an associated increase of serum acetylcholinesterase with triglyceride levels in diabetics and may point to a possible association between increased serum acetylcholinesterase and vascular complications in Jamaican diabetics. PMID- 1404461 TI - Ethnic distribution of primary central nervous system tumors in Washington, DC, 1971 to 1985. AB - An ethnic analysis was made of 8947 cases of primary central nervous system (CNS) tumors seen at the Armed Forces Institute of Pathology (AFIP), Washington, DC, from 1971 to 1985. Results showed a slightly higher frequency of primary CNS tumors in whites than in blacks with a white:black case ratio of 9:1 against the white:black population ratio in the United States of 7.4:1. Gliomas appeared to be twofold more frequent in whites than in blacks with a white:black case ratio of 12.1:1. However, meningiomas and pituitary adenomas were more common in blacks with a white:black case ratio of 6.7:1 and 4.2:1, respectively. When these results were compared with the results of a previous identical study using similar materials collected at AFIP from 1958 to 1970, the relative paucity of gliomas and higher frequency of meningiomas and pituitary adenomas in American blacks is again confirmed, thus re-emphasizing the importance of genetic factors in the genesis of primary CNS tumors. The remarkable decreasing white:black case ratio of primary CNS tumors as a whole (9:1 compared with 13.7:1) since 1970 probably reflects the socioeconomic improvement of American blacks during the same period. PMID- 1404462 TI - Sexual behaviors of African-American male college students and the risk of HIV infection. AB - A survey of the rates of sexually transmitted diseases and protective sexual behaviors among a population of African-American male college students demonstrates that although monogamy, avoidance of casual sexual activity, and the avoidance of the use of drugs and alcohol during sexual activity tends to decrease the risk of exposure to human immunodeficiency virus, consistent condom use is the only sexually related behavior that is significantly protective. PMID- 1404463 TI - Fluoroscopic chest tube insertion and patient care. AB - Catheters and chest tubes may be placed under fluoroscopic control to reduce pleural effusions. This procedure has been adopted as a routine procedure at the UCLA School of Medicine in Los Angeles, California to improve patient care. This technique was modified for the placement of large chest tubes, which can be placed by a radiologist without multiple attempts or complications. Our experience with 2234 patients who underwent this procedure between 1977 and 1990 is described. PMID- 1404464 TI - Macular degeneration: how big is the problem? AB - Almost every report on macular degeneration begins with a somber reminder that macular degeneration is the single most common cause of blindness in the elderly in the United States and Europe. Almost every report also confirms that there is no known successful approach to slowing, stopping, reversing, or preventing this syndrome. In the light of these devastating statements, it is difficult to explain the paucity of information about the disease process in general and its epidemiologic implications in particular. What little is known deals with prevalence rates; no figures are available regarding the incidence. Additionally, almost without exception, the prevalence numbers are based on the assumption that macular degeneration is a binomial (black and white) problem. However, macular degeneration, like all chronic diseases, exists in a potentially infinite number of shades of gray. Hence, when viewed as an achromatic continuum, macular degeneration is more prevalent than generally believed. Recognizing this disorder earlier invites the greater possibility of a cure or primary prevention. PMID- 1404465 TI - Painful subacute thyroiditis (de Quervain's thyroiditis). AB - Painful subacute thyroiditis (de Quervain's thyroiditis) usually occurs in association with systemic viral illnesses. This disorder may be manifested in various clinical forms. Primary care physicians must be aware of the clinical features of this disorder to make the correct diagnosis and treat appropriately. Three cases are reported to illustrate the different clinical manifestations of this disorder. PMID- 1404467 TI - The legacy of William Montague Cobb, MD, PhD (1904-1990). PMID- 1404466 TI - Complications of laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy with lasers or cautery is a feasible, effective, and worthwhile operative procedure that is subject to morbidity and mortality. There is unequivocal evidence that the complication incidence is directly related to the training and experience of the surgeon, applicability of basic principles of gallbladder and common duct surgery, and preventive measures toward iatrogenic injuries in gallbladder surgery. Continued and sustained investigation in laparoscopic cholecystectomy, technological developments in equipment, and the continued education of the surgeon in the applicability and use of laparoscopic cholecystectomy, intraoperative cholangiography, and choledocholithotomy are essential. At the St Francis Medical Center, Pittsburgh, Pennsylvania 1009 laparoscopic cholecystectomies with lasers or cautery were performed between March 1989 and October 1991. There were 32 (3%) abandoned laparoscopic cholecystectomies with alternative open cholecystectomy. There were six extrahepatic ductal injuries and a complication incidence of 10.9%. The mortality rate was 0.38%. The average length of stay was 2 days. In comparison with standard cholecystectomy, laparoscopic cholecystectomy is a competitive and superior procedure in selected circumstances. PMID- 1404468 TI - Choroid plexus tumor in a child. AB - A 5-month-old infant is reported who presented with fever, nonspecific symptoms, a rapidly enlarging head, and a regression in motor development. Investigations subsequently confirmed the diagnosis of a choroid plexus papilloma. PMID- 1404470 TI - A patient's perspective on sickle cell disease treatment. PMID- 1404469 TI - Fibular strut grafting for fibrous dysplasia of the femoral neck. AB - When fibrous dysplasia affects the femoral neck, normal bone is replaced by fibro osseous dysplastic bone that is both mechanically weakened and biomechanically abnormal. Surgical management is recommended for persistent pain, progressive deformity, or impending fracture. Surgical options include curettage and cancellous bone grafting, osteotomy and nail-plate fixation, intramedullary rodding, and cortical bone grafting. We present the case of a patient with a painful, dysplastic lesion of the femoral neck who underwent cortical bone grafting using dual fibular strut grafts. To ensure long-term graft incorporation, the fibular cortical grafts bridged the lesion in the femoral neck and were securely anchored to the normal bone of the lateral femoral cortex and a head of the femur. No supplemental internal fixation was required. The biological basis for success of the fibular strut grafting procedure is that creeping substitution of the cortical graft necrotic bone does not replace the interstitial lamellae, which persist to lend structural support. Fibular strut grafting is an excellent procedure for fibrous dysplasia of the femoral neck. PMID- 1404471 TI - The African-American physician and community interaction. PMID- 1404472 TI - Gerontologists or geriatricians? That is the question. PMID- 1404473 TI - AIDS/HIV crisis in developing countries: the need for greater understanding and innovative health promotion approaches. AB - Epidemiologic data on morbidity and mortality have shown that the acquired immunodeficiency syndrome/human immunodeficiency virus (AIDS/HIV) epidemic is relatively widespread in the developing countries of the world, especially in the already economically deprived regions of Sub-Saharan Africa. Africa is estimated to have approximately 5 million seropositive individuals, and by the year 2000, this number is expected to include 10 million HIV-infected children. Improved control over this epidemic can only come through a greater understanding of the specifics of the disease and, eventually, the introduction of more effective and innovative health promotion campaigns targeted at medical personnel, traditional healers, families, and persons with AIDS. Comprehensive health promotion campaigns, carefully using mass media strategies in addition to more community based programs, all operating under "decentralized" AIDS control programs, are reasoned to be the most efficacious approach that African and other developing countries can use to successfully contain the AIDS/HIV epidemic. Given the reality of the following factors: Pattern II (ie, transmission of AIDS via heterosexual sexual activity) is the main mode of HIV transmission in Africa, the traditional dominant roles males have in sexual relations, and the positive relationship between sexually transmitted diseases and AIDS, health promotion campaigns must focus specifically on addressing at-risk culturally related sexual values and behaviors in African communities. Failure to address these and other related factors will certainly lead to an escalation of the AIDS/HIV epidemic in Africa and, therefore, concomitant devastation in the human and societal realms of the region. PMID- 1404474 TI - Amelioration of nephrotoxicity associated with synthetic oxygen transport media. AB - Use of synthetic oxygen transport media offers the potential advantages of reducing requirements for coadministration of blood products and oxygen at the scene of mass casualty situations. Previous studies have shown perfusions of isolated kidneys with stroma-free hemoglobin (SFH) to be physiological while those with Fluosol-DA (20% FDA) have been associated with low glomerular filtration rate, urinary flow rate, and fractional reabsorption of sodium and potassium (FrNa+ and FrK+). In the present studies, perfusions with SFH/FDA mixtures showed normal glomerular filtration rate, a 50% lower urinary flow rate, and FrNa+ values 3% to 5% higher than SFH controls. Compared with 20% FDA perfusions, nephrotoxic effects of SFH/FDA combinations were moderate. Compared with SFH/FDA mixtures, perfusion with 20% FDA showed lower urinary flow and glomerular filtration rates. Ultrastructural assessment of glomerular filter revealed that FDA emulsion particles were adherent to epithelial podocytes. We conclude that resuscitation with a mixture of SFH and FDA may ameliorate the previously reported nephrotoxicity associated with the use of FDA alone. PMID- 1404475 TI - A prognostic role for ceruloplasmin in the diagnosis of indolent and recurrent inflammation. AB - Ceruloplasmin is increased in infections, inflammatory diseases, and neoplastic diseases and may be scarcely visible to the naked eye because it imparts a faint green color to the serum. This poses an interesting question as to a possible prognostic role for ceruloplasmin in the diagnosis of persistent or recurrent infection. The clinical course of 50 patients with tainted serum was reviewed retrospectively and ceruloplasmin levels correlated with diagnosis and outcome. Group I consisted of 20 healthy controls with normal ceruloplasmin levels: 35.1 +/- 2.0 mg/dL (range 25 to 45 mg/dL). Group II was made up of 23 surgical patients; 10 of these patients had elevated levels of ceruloplasmin, nine of whom had significant infections (64.2 +/- 3.2 mg/dL), and one patient was on estrogen (73.7 mg/dL). Group III consisted of 27 medical patients; 25 of these patients had elevated levels of ceruloplasmin, 20 of whom had infections (54.1 +/- 2.6 mg/dL), and five had malignancies (61.0 +/- 3.0 mg/dL). Ceruloplasmin levels were consistently elevated in all patients with infections relative to controls (P less than .001) with a variable response in other disease states. Therefore, ceruloplasmin may be useful as a serum marker for indolent or recurrent infections. PMID- 1404476 TI - Civilian field surgery in the rural trauma setting: a proposal for providing optimal care. AB - Rural trauma presents unique problems for surgical care. While military surgeons are prepared to provide care at or near the scene of battle, civilian literature is devoid of reports for care provided by surgeons at sites of injury occurrences. Although these injuries are infrequent, they are more likely to occur in rural trauma settings. This article describes two cases of extremity injury that required amputation at the scene and presents a proposal for swift mobilization of appropriately trained surgeons to the scene with adequate instrumentation and lighting, which can significantly reduce the morbidity and mortality of these victims. PMID- 1404477 TI - Characteristics of high-risk adolescent outpatients with treponemal antibody. AB - This study analyzes variables associated with syphilis infection among adolescents attending a public medical clinic in the District of Columbia. All adolescent clinic patients found to have Treponema pallidum antibody from June 1, 1989 through June 1, 1990 were included in the study. Medical records were reviewed for the following data: age, sex, presence or absence of court jurisdiction over the patient, chief complaint, concurrent infections, and the clinical stage of syphilis. The study population included 52 patients. The results revealed that male patients carry a higher risk of remaining undetected because only one third acknowledged any complaints prior to examination. This cohort study illustrates the predilection of syphilis for the indigent and underserved. Moreover, it highlights that insidious disease in adolescents is often unsuspected and undetected until routine screening tests are performed. PMID- 1404478 TI - Extracorporeal shock wave lithotripsy for radiolucent stones. AB - Eleven patients with radiolucent urinary calculi were treated with shock wave lithotripsy. Nine of these patients experienced successful fragmentation of their stones and subsequent spontaneous passage of the calculi fragments. The majority of the stones were composed of uric acid alone or a mixture of uric acid and calcium oxalate. One stone with metabolites of triamterene also fragmented well. Uric acid calculi can be treated successfully with shock wave lithotripsy using adequate visualization by contrast injection. PMID- 1404479 TI - Risk factors for neuroleptic malignant syndrome. AB - Neuroleptic malignant syndrome, a rare and potentially fatal complication of antipsychotic drugs, is poorly understood. Equally poorly understood are the risk factors of neuroleptic malignant syndrome. Long-term and parenteral treatment with high doses of neuroleptic drugs are implicated as risk factors for the syndrome. Recently, attention has been drawn to the frequency of neuroleptic malignant syndrome in patients treated with a combination of haloperidol and lithium. This article reports a case in which the patient's risk factors for neuroleptic malignant syndrome included not only haloperidol and lithium but also a predisposition to substances of abuse. PMID- 1404480 TI - Prevalence of Lyme disease infection in Oklahoma. AB - Even though Lyme disease probably existed in Oklahoma prior to 1975 when the disease was first reported in Connecticut and even though ecological conditions favor a high prevalence, an unexpectedly low rate was evidenced in both a serological survey and the number of cases reported to the Oklahoma State Department of Health. Lyme disease does not appear to pose a significant public health threat in Oklahoma at the present time; however, the the presence of all the necessary factors for transmission and the rapidly increasing number of cases reported in nearby areas merits continued surveillance in this state. The need for consistent case definition is discussed. PMID- 1404481 TI - Mortality in the slave and white populations of Natchitoches Parish, Louisiana, 1850. AB - A review of mortality from the 1850 census mortality schedules of Natchitoches Parish, Louisiana has provided a snapshot of the health conditions of African American slaves. The cause of death was abstracted from the mortality schedule and categorized according to the ninth revision of the Manual of the International Classification of Diseases. Children under the age of 9 accounted for 44% of the total mortality. Sixty-four percent of all deaths recorded occurred in the slave population. Sixty-two percent of the slave deaths occurred in the male population. Leading causes of death were helminthiasis, whooping cough, fever, cholera, and pneumonia. Reports of mortality due to Cachexia Africana (dirt eating) among slaves are discussed. PMID- 1404482 TI - Reevaluation of dioxin bioconcentration and bioaccumulation factors for regulatory purposes. AB - Bioconcentration factors (BCF) or bioaccumulation factors (BAF) reported for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) in aquatic environments encompass a wide range of values, from less than 1000 to 189,000 l/kg. These values are based on concentrations of TCDD in various environmental media including water, sediment, or food. Under the Federal Water Pollution Control Act and its enabling regulations (40 CFR 100-140, 400-470), point source discharge limits are established so that the nominal receiving water concentration will not exceed the water quality criterion. To be consistent with this regulatory process, the water quality criterion should also be calculated using an accumulation factor that is based on a nominal water concentration. The regulatory process for developing a water quality criterion for TCDD requires the selection of a BAF that describes the relationship between the source to be regulated and the fish tissue concentration. PMID- 1404483 TI - In vitro embryotoxicity of petroleum creosote monitored via mouse preimplantation embryo culture. AB - A mouse preimplantation embryo culture system was utilized to characterize the in vitro embryotoxicity of petroleum creosote (PC), a complex mixture of aliphatic and polycyclic aromatic hydrocarbons. ICR mouse embryos, collected on d 3.5 of gestation (blastocyst stage), were exposed for 1 h to varying concentrations of petroleum creosote in serum-supplemented culture medium. Parallel embryo cultures were exposed to PC in medium supplemented with rodent hepatic S9 microsomal fractions to monitor the role of bioactivation in PC-induced embryotoxicity. Embryos were subsequently cultured in control medium for 72 h and observed for viability as well as specific, time-dependent developmental end points--hatching and attachment to the culture dish at 48 h, and trophoblastic outgrowth with a distinct inner cell mass at 72 h. Embryonic viability varied in inverse proportion to PC concentration. Petroleum creosote caused embryolethal effects at concentrations of 33 micrograms/ml of culture medium and 54 micrograms/ml. Embryotoxicity was not observed at 22 micrograms/ml. Culture supplementation with rodent hepatic S9 fractions did not modify, either qualitatively or quantitatively, the embryotoxicity of PC in vitro. These findings implicate PC as a prenatal toxicant and support environmental and human health concerns regarding PC exposure from PC-containing chemical waste sites. PMID- 1404484 TI - Performance of an aquatic multispecies system in evaluating the effects of a model microbial pest control agent on nontarget organisms. AB - A recirculating multispecies test system was developed in conjunction with a study of the fate and persistence of a model microbial pest control agent on non target marine and freshwater organisms. The basic unit of the system was a 113-I glass aquarium with vertical biological filters in the center of the aquarium, such that two compartments were formed. This allowed the sequestration of predator and prey species within the same system. Organisms from six phyletic groups were subjected to a genetically altered strain of Pseudomonas putida for 15-29 d in either artificial seawater or fresh water. The system was able to maintain the animals for these periods with a minimum of maintenance. Additionally, the system design lent itself to disinfection, dismantling, and rebuilding between experiments with a minimum of labor, and has potential for longer-term studies. PMID- 1404485 TI - Procedure for evaluating changes in respiratory symptoms of experimentally asthma induced guinea pigs by a personal computer. AB - An automated system was developed for evaluating changes in respiratory symptoms in guinea pigs over a long period with a personal computer. The data on breathing curves obtained with a body plethysmograph were analyzed to determine respiratory rate, expiration/inspiration ratio, ventilation ratio, and other parameters. With this system, respiratory changes in guinea pigs, such as increase or decrease of respiratory rate, expiration/inspiration ratio, and ventilation ratio, and death of animals could be easily observed. Investigation of delayed respiratory response to Candida albicans in sensitized guinea pigs and of the effects of SO2 or NO2 exposures on its response was carried out using this system. Respiratory changes in delayed respiratory response were mostly increased respiration rate and succeeding expiratory prolongation being noted just before death. In the influences of SO2 or NO2 exposure on delayed respiratory response, increase of respiratory rate in NO2 and expiratory and inspiratory prolongation in SO2 were found. This system should prove useful for evaluating changes in respiratory symptoms due to toxic agents, medicines, and air pollutants in small animals. PMID- 1404487 TI - Acute toxicity, distribution, and metabolism of 2,4,6-trinitrophenol (picric acid) in Fischer 344 rats. AB - Picric acid (2,4,6-trinitrophenol) is widely used in industry, by the military, and as a research/clinical chemistry reagent. Characterization of the toxicity of this chemical has been limited. Thus the acute toxicity, distribution, and metabolism of picric acid were investigated using Fischer 344 rats. The LD50 for picric acid following oral dosing of male and female rats was established as 290 and 200 mg/kg, respectively. Blood gas analysis indicated severe acidosis during acute intoxication. Metabolism of picric acid was limited to reduction of nitro groups to amines. Metabolites isolated from urine included N-acetylisopicramic acid (14.8%), picramic acid (18.5%), N-acetylpicramic acid (4.7%), and unidentified components (2.4%). Approximately 60% of the parent picric acid was excreted unchanged. The plasma half-life for picric acid was 13.4 h with a gut absorption coefficient (ka) of 0.069 h-1. Twenty-four hours following oral administration of [14C]picric acid (100 mg/kg), the primary depots of radioactivity (per gram tissue basis) were blood, spleen, kidney, liver, lung, and testes. Respective tissue/blood ratios were 0.37, 0.31, 0.28, 0.26, and 0.22. All other tissue assayed had partition ratios < 0.20, with brain and adipose tissue having the least amount of radioactivity. Tissue/blood ratios were essentially maintained over a 48-h postadministration period. Binding (in vitro) of [14C]picric acid to plasma proteins (whole blood preparations) demonstrated both high- and low-affinity binding sites, with dissociation constants of 3.18 x 10(-6) and 2.85 x 10(-4) M, respectively. The findings of this investigation provide information on the acute toxicity, metabolism, and distribution of picric acid, which can be used in risk assessment analyses and in the design of subchronic and chronic toxicity tests. PMID- 1404486 TI - Selected pesticide residues and metabolites in urine from a survey of the U.S. general population. AB - Residues of toxic chemicals in human tissues and fluids can be important indicators of exposure. Urine collected from a subsample of the second National Health and Nutrition Examination Survey was analyzed for organochlorine, organophosphorus, and chlorophenoxy pesticides or their metabolites. Urine concentration was also measured. The most frequently occurring residue in urine was pentachlorophenol (PCP), found in quantifiable concentrations in 71.6% of the general population with an estimated geometric mean level of 6.3 ng/ml. Percent quantifiable levels of PCP were found to be highest among males. Quantifiable concentrations of 3,5,6-trichloro-2-pyridinol (5.8%), 2,4,5-trichlorophenol (3.4%), para-nitrophenol (2.4%), dicamba (1.4%), malathion dicarboxylic acid (0.5%), malathion alpha-monocarboxylic acid (1.1%), and 2,4-D (0.3%) were found, but at much lower frequencies. No quantifiable levels of 2,4,5-T or silvex were found. Preliminary analyses showed an apparent relationship between residue concentration and two measures of urine concentration (osmolality and creatinine). A large segment of the general population of the United States experienced exposure to certain pesticides, including some considered biodegradable, during the years 1976-1980. PMID- 1404489 TI - Ovine urinary metabolites of ethoxyquin. AB - Metabolites of ethoxyquin (EQ, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline) in the urine of sheep and rats were separated and identified by gas chromatography mass spectrometry (GC-MS). Sheep were given diets containing EQ or EQ.HCl (0.5% of total diet) and urine samples were collected for the first 24 h and for another 24-h period after 12 d of feeding. Rats were given EQ/corn oil (0.08 g EQ/d/rat) orally for 7 d and urine samples were collected at ambient temperature for a 24-h period following 6 d of dosing. The urine samples were extracted with ethyl acetate at pH 5, and the concentrated extracts were analyzed by GC-MS. Ethoxyquin was identified in all sheep urine samples collected during the first 24 h of feeding, and EQ and hydroxylated EQ were identified in all urine samples collected after 12 d of feeding. In contrast, EQ, hydroxylated EQ, and dihydroxylated EQ were identified in urine collected from rats fed EQ for 7 d. PMID- 1404488 TI - Investigations in the use of mice exposed to mycotoxins as a model for growing pigs. AB - A series of experiments was conducted to determine the feasibility of using mice to screen for possible dietary mycotoxin interactions before testing them with swine. Selected mycotoxins, deoxynivalenol (DON) and T-2 toxin, were fed to young mice, alone and in combination. The severity of effects on body weights caused by DON (0-20 mg DON/kg diet) was more pronounced in a dose-related manner when the animals were exposed to contaminated diets starting at 21 d of age than at 28 d (Experiment 1) as reflected in the analysis of variance. The relative variance among diets after 7 d was twice as great for the younger than for the older mice. In both age groups, the weight gain response was linear, similar to that seen in growing swine. In Experiment 2, a significant (p < .05) diet type x DON interaction for food consumption evident after 7 d, indicated that the effect of DON depended on the type of diet (freeze-dried vs. regular mash). There was no difference in food efficiency between diet type, but a strong dose-dependent effect due to DON was observed. When DON and T-2 toxin were fed together to young mice, a significant (p < .001) linear decrease in weight gain and food consumption was observed after 7 d on the contaminated diet as the toxin concentration increased. PMID- 1404490 TI - Interaction of multiple nuclear proteins with the promoter region of the mouse 68 kDa neurofilament gene. AB - Four brain-specific, DNase I hypersensitive sites (HSS) have been mapped to the 5' flanking region of the mouse 68-kDa neurofilament gene. These sites are contained within a 1.7-kb sequence that confers neuronal specificity of expression of this gene in transgenic mice. To identify DNA sequences that might be involved in gene regulation, the HSS situated near the promoter region has been analyzed by gel mobility shift assays and DNase I footprinting to investigate protein binding sequences. Of particular interest are two footprints localized to a 9-nucleotide sequence that flanks both the light and medium neurofilament gene in mouse and to a sequence that demonstrates partial homology to several promoter regions, including element-1, a motif required for neuron specificity in Drosophila. A prominent footprint was also detected at a sequence that contains a near-perfect palindrome centered at a PstI restriction site. PMID- 1404491 TI - Molecular cloning of a novel mRNA using an antibody directed against synaptic glycoproteins. AB - It has been suggested by a number of investigators that glycoproteins may play a role in the development and/or maintenance of synapses in the mammalian CNS. For many synaptic glycoproteins, however, little precise structural or functional information is available. In an effort to isolate probes specific to individual glycoproteins, we have screened a rat brain cDNA expression library with a mixed polyclonal antibody directed against concanavalin A-binding synaptic junctional glycoproteins. Using this approach, we have previously reported the cloning of SC1, a putative extracellular matrix glycoprotein found in adult brain (Johnston et al., Neuron 2:165-176, 1990). We now report the cloning and characterization of a second novel cDNA, which has been designated SC2. Northern blots show that this cDNA recognizes a 1.2-kb mRNA that is present throughout postnatal development in the rat. It is expressed at high levels in brain and is also found at lower levels in several other tissues. In situ hybridization suggests that the SC2 mRNA is strongly expressed by many types of neurons. Sequence data reveals a single open reading frame in the cDNA, encoding a putative hydrophobic protein with a calculated molecular weight of 36.1 kDa. Sequence analysis reveals some similarity between SC2 and 5 alpha-reductase, a microsomal membrane protein important in testosterone metabolism. PMID- 1404493 TI - Immunohistochemical and biochemical analysis of N-cadherin expression during CNS development. AB - The expression of the calcium-dependent adhesion molecule N-cadherin during chick embryo central nervous system (CNS) development was examined by immunohistochemistry and electrophoresis and immunoblotting. During histogenesis, N-cadherin is expressed at high levels in a uniform fashion in many regions of the CNS. However, during later stages of development, expression becomes restricted to the ependymal cells lining the ventricular system and in the choroid plexus. This down-regulation was confirmed by both immunohistochemical and biochemical techniques. The program of expression lags behind in the cerebellum in concert with the delayed development of this region of the brain. A high level of N-cadherin was found to be expressed in the brainstem and spinal cord floorplate, while a low level was detected at the optic nerve head. The results indicate that while, in general, the program of N-cadherin expression is similar in the retina and the brain, certain structures unique to the eye and brain express locally high or low levels of this adhesion protein. PMID- 1404492 TI - Analysis of promoter activity and 5' genomic structure of the neural cell adhesion molecule L1. AB - To gain insight into the molecular mechanisms underlying the regulation of expression of the neural cell adhesion molecule L1 and into the exon-intron structure of the L1 gene, a genomic clone from the mouse was characterized. The clone was identified by screening an EMBL3 library with an L1-specific cDNA probe and comprises approximately 15 kb, in which the first 2,206 nucleotides of the coding region are included. Of the 5 of 6 immunoglobulin (Ig)-like domains sequenced, all are encoded by 2 exons, with the first exon being smaller than the second. The exon encoding the signal peptide is separated from a mini-exon containing 15 bp by a large intron, approximately 2.6 kb in length, whereas the other introns are smaller, with the coding information for the Ig-like domains 3 5 clustered in a 1,643-bp-long fragment with introns only 110-217 bp in length. The 5' upstream region of the clone comprises 5 kb, with the first 112 bp lying upstream to the coding sequence and containing a start site for transcription. No consensus sequence for a TATA box was found. Consensus DNA sequences for the binding of the gene products of Hox 1.3, engrailed and bicoid, are localized upstream to the transcription start site. A 1,262-bp fragment containing part of the first exon showed promoter activity in neuroblastoma cells, but hardly in L cells and not in CHO cells, indicating that this fragment is sufficient for neural cell directed promoter activity. PMID- 1404494 TI - Secretion of apolipoprotein E by an astrocytoma cell line. AB - Apolipoprotein (apo) E is a predominant protein in developing mammalian brain and in damaged peripheral nerve. Of particular interest is the observation that astrocytes in the central nervous system cease to produce apoE after nerve damage, whereas an increase in apoE production results after peripheral nerve injury. Differences in the response to injury with regard to the production of apoE may be related to dissimilarities in the abilities of the central and peripheral nervous systems to regenerate. As there are few data concerning the regulation of apoE gene expression in extrahepatic tissues, we employed a human astrocytoma cell line (CCF-STTG1) as a model to study apoE production in astrocytes. CCF-STTG1 cells secreted apoE constitutively in serum-free media. Cholesterol added to the media as cholesterol:phospholipid liposomes (2-100 micrograms/ml) or as human plasma LDL increased the amount of apoE secreted into the media, but had little or no effect on the relative abundance of apoE mRNA. By contrast, the commercially available triglyceride-phospholipid emulsion Intralipid added at dilutions of 1:50 to 1:500 caused a total inhibition of apoE secretion by the cells, but again, little change was noted in the relative abundance of apoE mRNA. Insulin (5 micrograms/ml) caused a 45-55% reduction in the amount of apoE secreted by the astrocytoma cells. Glucagon (5 micrograms/ml), on the other hand, did not increase apoE secretion, and apoE mRNA concentrations were not affected by either hormone treatment. ApoE was secreted from the astrocytoma cells associated with particles of plasma VLDL to IDL and HDL size. After feeding the cells with 20 micrograms/ml cholesterol as cholesterol:phospholipid liposomes, an increased proportion of apoE was secreted associated with the larger VLDL to IDL size particles, with a concomitant decrease in the proportion associated with the smaller HDL-size particles. When cells were incubated with 5 micrograms/ml insulin, most of the apoE was associated with the HDL-size particles. When cholesterol:phospholipid liposomes were added in the presence of insulin virtually all of the secreted apoE was found associated with the VLDL to IDL size particles. In summary, the regulation of apoE production in CCF-STTG1 cells in many respects resembles that of other cells, including hepatocytes. However, it is clear that there remain to be identified cell specific factors which regulate apoE production in astrocytes. The CCF-STTG1 cell line promises to provide a suitable model to investigate these questions. PMID- 1404495 TI - Advances in the use of the fluorescent probe fura-2 for the estimation of intrasynaptosomal calcium. AB - Fura-2 has been used to measure intracellular Ca2+ with great success in a variety of cell and subcellular preparations, including synaptosomes. There is, however, a great deal of variability in the reported estimates of resting intrasynaptosomal Ca2+ ([Ca2+]i). Fura-2 AM is highly lipophilic and passes readily across the plasma membrane into the cytoplasm, where it is de-esterified and trapped. The lipophilicity of fura-2, however, promotes the formation of micelles in aqueous media, which may impede the passage of the probe across cell membranes. Our results suggest that some of the variability in the reported [Ca2+]i estimates may be related to fura-2 de-esterification and loading efficiencies. The use of the nonionic detergent pluronic F-127 is recommended to prevent the formation of fura-2 micelles. The use of a detergent is not always an acceptable practice, however, especially in studies in which detergent-lipid interactions may influence membrane parameters. We found that fatty acid free bovine serum albumin (BSA) (0.25%) greatly increases the intrasynaptosomal concentration of the probe, resulting in a significant increase in the signal-to noise (S/N) ratio. The mechanism appears to be independent of effects of BSA on synaptosomal integrity and directly related to the prevention of fura-2 micelle formation, as evidenced by light spectroscopic scattering measurements. Thus, BSA appears to keep the probe in a form that crosses the synaptic plasma membrane more readily. The effectiveness of BSA in improving the loading of fura-2 into synaptosomes was comparable to the detergent pluronic F-127, making it possible to measure [Ca2+]i without compromising membrane integrity. PMID- 1404496 TI - Laminin and its neurite outgrowth-promoting domain in the brain in Alzheimer's disease and Down's syndrome patients. AB - Immunocytochemistry, radioimmunoassay, immunoblotting, Northern analysis, and polymerase chain reaction (PCR) technique were applied to investigate the distribution of laminin and its neurite outgrowth domain in brains of neuropathologically verified cases of Alzheimer's disease and Down's syndrome. New antibodies against a neurite outgrowth domain of laminin were characterized and were used in localization of this peptide antigen in the human brain. Laminin was found as large punctate deposits in all plaques in the affected brains. Laminin synthesis was increased as assessed by RNA blotting and immunoblotting, and glial cells were heavily immunoreactive with antibodies for a neurite outgrowth-promoting peptide antigen of the B2 chain of laminin. This peptide antigen not only was produced by glial cells but also was deposited in the brain tissue. As this peptide antigen promotes neurite outgrowth at low concentrations, and is specifically neurotoxic at high concentrations, it may play a synergistic role with other molecules in inducing the sprouting and neurodegeneration occurring in brains of patients with either Alzheimer's disease or Down's syndrome. PMID- 1404497 TI - Morphological differentiation and proteoglycan synthesis regulate Alzheimer amyloid precursor protein processing in PC-12 and human astrocyte cultures. AB - A morphologically differentiated strain of rat pheochromocytoma (PC-12H) metabolically labeled with [35S]methionine and incubated with a phorbol ester displayed reduced 140-kDa and increased 15 kDa bands relative to cells incubated without phorbol ester after immunoprecipitation with antisera elicited by the C terminal peptide of the Alzheimer amyloid precursor protein (APP). These bands correspond to glycosylated full length APP and a C-terminal fragment previously reported by Anderson et al. (Neurosci. Lett. 120:126-128, 1991) to result from a cleavage within the amyloidotic A4 region of APP, which releases a 120 kDa extracellular fragment. The 15 kDa fragment, not immunoprecipitated with an antisera elicited by the N-terminal portion of A4 amyloid, is nonamyloidogenic. Incubation of these cells with p-nitrophenylxyloside, known to inhibit proteoglycan formation, also increased this nonamyloidogenic cleavage of APP. In contrast to these results, an undifferentiated low passage PC-12-L strain constitutively displayed rapid nonamyloidogenic APP cleavage. Incubation of PC-12 L with phorbol ester did not affect the relative abundance of 140 or 15 kDa bands. Growth of PC-12-L with 7 S NGF or dibutyryl cAMP resulted in increased morphological differentiation and decreased APP cleavage which was now phorbol inducible. Similar analyses of dividing and senescent human astrocytes and normal and F-AD fibroblasts indicate 5-fold lower rates of mid-A4 APP cleavage. Phorbol esters decreased the 140 kDa APP band without affecting the intensity of the 15 kDa band in these cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404498 TI - Effect of a discrete dorsal forebrain lesion in the rat on the expression of neuronal and glial-specific genes: induction of calmodulin, NF-L, SC1, and GFAP mRNA. AB - The influence of a localized tissue injury on the expression of genes encoding specific neuronal and glial proteins was examined using in situ hybridization. A pronounced induction of neuron-specific calmodulin (CaM) mRNA was evident within cells proximal to the wound site by 2 hours following a cortical lesion in rats. By 12 hours postlesion, intense signal corresponding to CaM mRNA was found to extend 1 mm from the wound site. Changes in the expression of mRNA encoding two additional neuronal proteins, the 68 kilodalton neurofilament protein and the extracellular matrix protein, SC1, were also evident at 12 hours following the cortical injury. Of the two glial proteins examined, a dramatic elevation in levels of mRNA for glial fibrillary acidic protein (GFAP) was observed at the wound site by 12 hours postlesion. This intense labeling corresponding to GFAP mRNA was evident in the ipsilateral glial limitans and hippocampus as well as in the contralateral glial limitans. In contrast, the pattern of labeling for the beta-subunit of the S100 protein did not differ from that of control animals at either of the postlesion intervals examined. This study identifies four genes, CaM, GFAP, SC1, and NF-L, which are induced following a localized cortical injury and which encode mRNA species enriched in specific cell-types in the central nervous system. PMID- 1404499 TI - Organ injury scaling. III: Chest wall, abdominal vascular, ureter, bladder, and urethra. PMID- 1404501 TI - Improved outcome with hypotensive resuscitation of uncontrolled hemorrhagic shock in a swine model. AB - Recent animal studies have shown that aggressive saline infusion may produce significant mortality in models of moderately severe (20-30 mL/kg) uncontrolled hemorrhage. The postulated mechanism is an increase in hemorrhage that accompanies restoration of normal blood pressure. Although aggressive saline infusion and restoration of blood pressure appear indicated when hemorrhage is potentially lethal (40-45 mL/kg), we hypothesized that the attempt to restore blood pressure with aggressive saline infusion would not improve survival. This study used a swine model of severe uncontrolled hemorrhagic shock to compare the effects of resuscitation to mean pressures of 40 and 80 mm Hg. Twenty-four immature swine, each with a surgical steel aortotomy wire in place, were bled rapidly from a femoral artery catheter to a mean arterial pressure (MAP) of 30 mm Hg. The aortotomy wire was then pulled, producing a 4-mm aortic tear and free intraperitoneal hemorrhage. When the pulse pressure decreased to 5 mm Hg, saline infusion was begun at 6 mL/kg/minute and continued as needed to maintain the following endpoints: group I (MAP = 40 mm Hg), group II (MAP = 80 mm Hg), and group III (no resuscitation). After a maximum saline infusion of 90 mL/kg, the infusate was changed to shed blood at 2 mL/kg/minute. Data were compared using analysis of variance and Fisher's exact test. One-hour survival was 87.5%, 37.5%, and 12.5% for groups I, II, and III, respectively. Intraperitoneal hemorrhage for the three groups was 8.2 mL/kg, 39.9 mL/kg, and 6.7 mL/kg. The amount of saline infused was 55.8 mL/kg in group I and 90 mL/kg in group II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404500 TI - A decision analysis of traumatic splenic injuries. AB - We created a decision analysis model of the nonsurgical management of traumatic splenic injuries to clarify the risk of hospital survival, overwhelming postsplenectomy infection (OPSI) deaths, and transfusion-related deaths. We reviewed 72 cases of splenic injury at our institution to identify our transfusion requirements for successful observation (0.5 units), observation failure (1.0 units), and surgical splenic management (1.6 units). Using our model and baseline probabilities determined from the literature, we compared the nonsurgical management of splenic injuries with immediate laparotomy and found an increase in hospital survival with observation, but an over two-fold increase in the risk of transfusion-related death. The OPSI deaths were not markedly different between the two strategies. Overall, we found decision analysis useful in identifying important variables such as the probability of nontherapeutic laparotomy death or missed injury, and in clarifying the risk of the nonsurgical management of splenic injuries with regard to transfusion-related deaths and OPSI deaths. PMID- 1404502 TI - Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: a preliminary report. AB - Although intravenous (IV) fluid therapy is routinely prescribed for hypotensive injury victims, there are concerns that elevating the blood pressure before hemorrhage is controlled may be detrimental. This is a preliminary report of an ongoing randomized study designed to evaluate the effect fluid resuscitation, delayed until surgical intervention, has on the outcome for hypotensive victims of penetrating truncal injury. In the first year, 300 consecutive patients with gunshot or stab wounds to the trunk who had a systolic blood pressure of 90 mm Hg or less were entered into the study. Patients were excluded from the outcome analysis because of death at the scene or minor injury not requiring surgical intervention. The remaining study patients were randomized into (1) an immediate resuscitation group (n = 96) for whom IV fluid resuscitation was initiated in the ambulance and in the emergency center before surgical intervention, or (2) a delayed resuscitation group (n = 81) for whom IV fluid resuscitation was delayed until the time of surgical intervention. The two study groups were found to be well balanced with respect to anatomic injury severity, pretreatment vital signs, survival probability, and preoperative treatment times. There were no significant differences in the rate of survival to hospital discharge (immediate resuscitation group, 56%; delayed resuscitation group, 69%). There were no significant differences in the rate of postoperative complications. Further study is necessary to determine if it is advantageous to delay fluid resuscitation until surgical intervention. PMID- 1404503 TI - Prospective validation of criteria, including age, for safe, nonsurgical management of the ruptured spleen. AB - One hundred twelve cases of blunt splenic rupture were prospectively entered (October 1987-October 1991) into surgical or nonsurgical management groups using these criteria for the nonsurgical group: hemodynamic stability+age less than 55 years+CT scan appearance of grade I, II, or III injury+absence of concomitant injuries precluding abdominal assessment+absence of other documented abdominal injuries. All ages were included and AAST injury scaling was used. Patients were grouped from the trauma room. The surgical treatment group included 66 patients (49 splenectomies, 17 splenorraphies). These patients were generally older and more severely injured, required more transfused blood, and a longer ICU stay. The nonsurgical group included 46 patients with 33 older than 14 years. There were 3 patients over the age of 55 years inappropriately included in this group, and nonsurgical therapy failed in all three. Statistical analysis (chi 2) showed that more splenic injuries were observed and more spleens were saved with these criteria applied prospectively compared with a previous retrospective series in the same institution. Our series had a success rate of 93%, and validates the criteria used for safe, nonsurgical management of the ruptured spleen and adds a new criterion: a maximum age of 55 years. PMID- 1404504 TI - Physician review improves hospital DRG reimbursement in injury. AB - This was a prospective study of all DRG reimbursed trauma patients discharged during an 11-month period. Initial DRGs were assigned by hospital coding specialists (HCS). A surgeon (SURG) subsequently reviewed each chart and assigned DRGs to maximize reimbursement. The data for 244 patients were: age = 36.5 years, Trauma Score (TS) = 13.8, Injury Severity Score (ISS) = 16.9, and length of stay (LOS) = 10.3 days. Total charges for the 244 patients were $4,261,208 with an initial HCS projected reimbursement of $1,687,963. The SURG review resulted in a total projected reimbursement of $1,956,476, an increase of $268,513 in revenue (p less than 0.001). Charges correlated strongly with LOS and ISS. The HCS-coded and SURG-coded reimbursements also correlated positively with LOS and ISS, but to a lesser extent. The SURG review of DRG assignment improved hospital reimbursement for the injured patients. However, this reimbursement fell well below hospital billings. PMID- 1404505 TI - Coming of age: 1992 presidential address, Western Trauma Association. PMID- 1404506 TI - Blunt colonic injury--a multicenter review. AB - During the past decade there has been a shift in the management of injuries of the colon to primary repair without a protective diverting colostomy. Unfortunately, reports concerning this practice contain relatively few patients with blunt trauma and it is unclear whether the principles established for penetrating injury should be applied in the setting of blunt colon injury. A retrospective review of 54,361 major blunt trauma patients admitted to nine regional trauma centers from January 1, 1986, through December 31, 1990, was conducted. Statistical analysis of the data collected regarding 286 (0.5%) of these patients who suffered colonic injury revealed: (1) injury to the colon is found in more than 10% of patients undergoing laparotomy following blunt trauma; (2) available diagnostic modalities are unreliable in detecting isolated colonic pathology; (3) primary repair of full-thickness injuries or resection and anastomosis may be safely performed without diversion; (4) gross fecal contamination is the strongest contraindication to primary repair. Further, delay of surgery, shock, and the timing of antibiotic administration were not associated with significantly increased morbidity. PMID- 1404507 TI - The clinical utility of computed tomographic scanning and neurologic examination in the management of patients with minor head injuries. AB - The evaluation and management of patients with minor head injury (MHI: history of loss of consciousness or posttraumatic amnesia and a GCS score greater than 12) remain controversial. Recommendations vary from routine admission without computed tomographic (CT) scanning to mandatory CT scanning and admission to CT scanning without admission for selected patients. Previous reports examining this issue have included patients with associated non-CNS injuries who confound the interpretation of the data and affect outcome. We hypothesized that patients with MHI and no other reason for admission with normal neurologic examinations and normal CT scans would have a negligible risk of neurologic deterioration requiring surgical intervention. To validate this hypothesis we studied 2766 patients with an isolated MHI admitted to seven trauma centers between January 1, 1988, and December 31, 1991. There were 1898 male patients and 868 female patients; injury was blunt in 99%. A neurologic examination and a CT scan were performed on 2166 patients; 933 patients had normal neurologic examinations and normal CT scans and none required craniotomy; 1170 patients had normal CT scans and none required craniotomy; 2112 patients had normal neurologic examinations and 59 required craniotomy. The sensitivity of the CT scan was 100%, with positive predictive value of 10%, negative predictive value of 100%, and specificity of 51%. The use of CT alone as a diagnostic modality would have saved 3924 hospital days, including 814 ICU days, and $1,509,012 in hospital charges. Based on these data, we believe that CT scanning is essential in the management of patients with MHI and that if the neurologic examination is normal and the scan is negative patients can be safely discharged from the emergency room. PMID- 1404508 TI - Pitfalls in the use of color-flow duplex ultrasound for screening of suspected arterial injuries in penetrated extremities. AB - We compared color-flow duplex ultrasonographic scanning (CFD) to arteriography in 67 patients who sustained 75 penetrating injuries to the extremities without obvious arterial injury. There were 72 negative and three (4.0%) positive CFD studies and no failed attempts. With arteriography as the "gold standard," CFD had a specificity of 99% and a sensitivity of 50%, positive and negative predictive values of 66% and 97%, and an accuracy of 96%. Small pseudoaneurysms were missed in an axillary and an aberrant radial artery, and a genicular artery pseudoaneurysm was misread as originating from the popliteal artery. Cautious interpretation of negative studies appears warranted, particularly in the axilla and in bifurcated arteries. Extremity arteries should be completely imaged to rule out aberrant anatomy. Questionable studies should be confirmed arteriographically. With these caveats, color-flow duplex scanning may be useful for screening extremities with penetrating injuries thought to harbor occult arterial injuries. PMID- 1404509 TI - The deleterious effects of intraoperative hypotension on outcome in patients with severe head injuries. AB - Prehospital or admission hypotension doubles the mortality for patients with severe head injury (SHI = Glasgow Coma Scale score less than or equal to 8). To our knowledge no study to date has determined the effects of intraoperative hypotension [IH: systolic blood pressure (SBP) less than 90 mm Hg] on outcome in patients with SHI. This study examined 53 patients who had SHI and required early surgical intervention (surgery within 72 hours of injury). All patients were initially normotensive on arrival. There were 17 patients (32%) who developed IH and 36 (68%) who remained normotensive throughout surgery. The mortality rate was 82% in the IH group and 25% in the normotensive group (p less than 0.001). The duration of IH was inversely correlated with Glasgow Outcome Scale using linear regression (R = -0.30; p = 0.02). Despite vigorous fluid resuscitation in the IH group, additional pharmacologic support was used in only 32%. These data suggest that IH is not uncommon after SHI (32%) and that it does have a significant effect on patient outcome. PMID- 1404510 TI - Impact of minimal injuries on a level I trauma center. AB - Overtriage (i.e.; transport of patients with minimal injuries to a trauma center) has been accepted as necessary to avoid missing clinically significant injuries. We reviewed our experience with 344 patients (ISS less than or equal to 4) who were admitted to a level I trauma center during a 2-year period. The trauma team was activated for 209 patients (TA), and emergency department referrals accounted for 135 (ED). One hundred seventy-three patients (TA = 64%, ED = 36%) met American College of Surgeons' Committee on Trauma (ACSCOT) field triage criteria (FTC). Mechanism of injury, especially ejection from a motor vehicle, was the most frequently utilized FTC indicator. We found no differences between the TA and ED groups relative to Trauma Score, Glasgow Coma Scale score, Injury Severity Score, length of stay, or ICU days. Mean total costs were higher for the TA group than for the ED group. The TA group had a higher nursing acuity level than the ED group. Compliance with FTC yields an inherent overtriage of minimally injured patients; however, noncompliance with FTC compounds the overtriage rate. Failure to comply with FTC is costly, labor intensive, and may represent misuse of the trauma system. We propose continual re-education of prehospital personnel, increased responsibility of all hospitals in the trauma center catchment area, and protocols for "downstaging" trauma resuscitation in minimally injured patients. PMID- 1404511 TI - Routine pelvic x-ray studies in awake blunt trauma patients: a sensible policy? AB - To evaluate the usefulness of routine pelvic x-ray films in the resuscitation of blunt trauma victims, 1395 patients were prospectively evaluated over a 13-month period. Of these, 810 (58%) were awake with Glasgow Coma Scale scores greater than or equal to 13 and were enrolled into the study. A history, with directed questions regarding pelvic pain, a clinical examination of the pelvis, and an anterior-posterior pelvic x-ray film (APPX) were obtained for each patient. Thirty-nine patients (5%) had fractures identified on the x-ray films. Of these patients with radiographically identified fractures, 34 (87%) complained of pain and had positive results on clinical examination, two (5%) either complained of pain or had positive results on examination and three (8%) had neither complaint of pain nor positive examination results. Of the 771 patients without fractures 743 (96%) lacked pain complaints or positive examination results. The likelihood of fracture was greatest in patients with complaints of pain and positive examination results (65%) followed by patients with either complaint of pain or positive examination results (16%). Only three (0.4%) of the 743 patients having no complaints of pain and a negative clinical examination had fractures diagnosed roentgenographically. These were minor fractures that did not affect the clinical course. Total charges incurred to diagnose pelvic fractures in this low-yield patient group were $88,028. We conclude that the practice of obtaining a screening APPX is not necessary or cost-effective in the management of awake blunt trauma patients who do not complain of pain and who have normal pelvic physical examination results. PMID- 1404513 TI - Analysis of organ procurement failure at an urban trauma center and the impact of HIV on organ procurement at a regional transplantation center. AB - A 42-month experience with 100 patients with fatal head injuries was analyzed to identify areas of organ procurement failure. Thirty-six patients were ineligible for organ donation. Reasons for exclusion included advanced age (7), sepsis (16), hepatitis (1), systemic illnesses (3), and HIV infection or risk (9). Resuscitation failure (17 patients) and late deaths from failed support (16 patients) left 31 potential donors. Of the 30 families asked to donate, 17 consented (56.7%). Annual consent rates were 25%, 71%, 75%, and 67%. Efforts to improve organ procurement should focus on resuscitation and physiologic support of potential donors. To assess the impact of HIV infection or risk on organ procurement, a 3-year experience of the regional transplantation center (RTP) was reviewed. Of 1,714 referrals to the RTP from 102 hospitals, 1,120 were from trauma centers. The incidence of rejection because of HIV risk or infection was significantly higher in the trauma center group than in the group from non-trauma centers, 17.2% versus 10.2% (p less than 0.004). A similar difference was noted between metropolitan and suburban hospitals (p less than 0.0001). Hepatitis risk was comparable, 3.9% vs. 3.2%. The risk of HIV infection is emerging as a factor limiting organ donation at urban trauma centers. PMID- 1404512 TI - Base deficit stratifies mortality and determines therapy. AB - OBJECTIVE: To determine the association of base deficit with mortality and other factors affecting mortality. DESIGN: Retrospective review. SETTING: Tertiary care center. PARTICIPANTS: Consecutive samples of 3791 trauma patients admitted with an arterial blood gas sample taken in the first 24 hours. MAIN OUTCOME MEASURES: Age, injury mechanism, head injury, shock (systolic blood pressure less than 90 mm Hg), Revised Trauma Score, TRISS probability of survival Ps, and mortality. RESULTS: Most (3038) patients (80.1%) exhibited a base deficit. Base deficit, age, injury mechanism, and head injury were associated with mortality using logistic regression. Age less than 55 years, no head injury, and a base deficit of -15 mmol/L were associated with 25% mortality. Age greater than or equal to 55 years with no head injury or age less than 55 years with a head injury and a base deficit of -8 mmol/L were associated with a 25% mortality. When shock was added to the model, all factors remained significant, and base deficit was supplemental to blood pressure. Base deficit also added significantly to the Revised Trauma Score and TRISS measurements. CONCLUSIONS: The base deficit is an expedient and sensitive measure of both the degree and the duration of inadequate perfusion. It is useful as a clinical tool and enhances the predictive ability of both the Revised Trauma Score and TRISS. PMID- 1404514 TI - Associated aortic rupture-pelvic fracture: an alert for orthopedic and general surgeons. AB - Blunt trauma patients with pelvic fractures have been shown to have a two-fold to five-fold increased risk of aortic rupture compared with the overall blunt trauma population. A retrospective review was performed to determine whether the relationship between aortic rupture and pelvic fracture could be further delineated using a pelvic fracture classification based on mechanism of injury. Of 4,157 consecutive blunt trauma patients, 371 (8.9%) had pelvic fractures, 34 (0.8%) had ruptured thoracic aortas and 12 had both injuries. When pelvic fractures were classified according to vector of force, 10 of 12 (83%) aortic ruptures occurred in patients with an anterior-posterior compression fracture pattern, an incidence of aortic rupture eight times greater than that of the overall blunt trauma population. There was no increased incidence of aortic rupture among patients with any other pelvic fracture pattern. We conclude that the previously reported association between aortic rupture and pelvic fracture can be further specified to include, predominantly, those patients with an anterior-posterior compression fracture pattern. PMID- 1404516 TI - Preventable complications and death from multiple organ failure among geriatric trauma victims. AB - We reviewed 374 consecutive trauma patients over age 65 years to determine (1) if the emergency room Trauma Score (TS) could predict mortality, thereby improving ICU triage, and (2) the frequency of preventable complications in patients who died (n = 31). Fifty-two percent of deaths (n = 16) occurred in patients with TS = 15 or 16. Multiple organ failure/sepsis (MOF/S) was the most common cause of death overall (42%) and was also the most frequent cause of death in patients with a TS = 15-16 (63%). Nonsurvivors in the TS = 15-16 subgroup were older (80.9 +/- 2.0 vs. 74.9 +/- 0.5 years, p less than 0.02) and had greater ISSs (15.8 +/- 3.7 vs. 8.0 +/- 0.4, p = 0.001) than survivors. Patients with a TS less than 15 suffered high overall mortality (45%). Preventable complications contributed to mortality in 32% of all deaths and in 62% of MOF/S deaths. Aggressive care to prevent avoidable complications may improve survival in elderly trauma victims. PMID- 1404515 TI - Percutaneous tracheostomy/gastrostomy in brain-injured patients--a minimally invasive alternative. AB - Tracheostomy and gastrostomy are frequent adjunctive procedures required in the management of patients with severe brain injuries to facilitate neurorehabilitation. We therefore evaluated the use of two minimally invasive surgical procedures, percutaneous tracheostomy (PT) and percutaneous endoscopic gastrostomy (PEG), in 27 patients with severe brain injuries. The mean age was 41 +/- 4 years, and 23 (85%) were men. All patients were intubated, and 19 (70%) required mechanical ventilator support on the day of PT/PEG. The endotracheal tubes had been in place for 1 to 21 days (mean, 8.7 +/- 0.8). All patients were stable from their acute brain injury; 13 had intracranial pressure (ICP) monitors in place. The Seldinger technique, as described by Ciaglia, was employed for PT. Following PT, a PEG was inserted by a modification of the Sachs-Vine "push" technique. We were uniformly successful in placing these access tubes. Complications were minor and not clinically significant. Three of 13 patients (23%) with ICP monitors had a transient rise in ICP related to PT and one of these patients developed local subcutaneous emphysema. Another patient experienced a mild cellulitis at the tracheostomy site. Of note, there were no PEG-related complications. In conclusion, PT and PEG are readily learned, minimally invasive procedures. In our experience with patients with severe brain injuries combined PT/PEG is a uniformly safe alternative to gain long-term access to the airway and gut. PMID- 1404517 TI - Acute stabilization of the cervical spine by halo/vest application facilitates evaluation and treatment of multiple trauma patients. AB - The management of acute cervical spine injuries has traditionally used bed-based skeletal traction until all non-neurologic injuries have been evaluated. This treatment method substantially hinders the ability to transport patients and to perform imaging studies and surgical procedures. In contrast, early application of a halo/vest apparatus provides immediate cervical stabilization and facilitates the diagnostic work-up and treatment of the patients with multiple injuries. The records of all 78 patients admitted from February 1988 through June 1991 who had acute cervical spine fractures, subluxations, or both with a risk of instability were reviewed. All patients were treated with halo/vests and no patient deteriorated neurologically following halo/vest application. Twenty-nine patients (37%) had a total of 55 associated injuries including long bone/pelvic fractures in 17, thoracic injuries in 13, closed head injuries in 11, facial fractures in 6, noncontiguous spinal fractures in 5, and abdominal injuries in 3. The mean injury Severity Score (ISS) was 18 (range, 9-54). While in the halo/vest, 43 patients (55%) had a total of 99 diagnostic studies completed and 46 patients (59%) had a total of 76 surgical procedures performed. There were 35 neurosurgical procedures on 32 patients and 41 non-neurosurgical surgical procedures on 24 patients. Over the past year, 20 of 21 patients (95%) had their halo/vest placed in the emergency department. The data demonstrate that many diagnostic and surgical procedures need to be performed on patients with unstable cervical spine injuries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404518 TI - Nutritional assessment using a pulmonary artery catheter. AB - To determine if oxygen consumption (VO2) derived from the Fick equation (FE) can be used to determine energy expenditure (EE), 29 paired indirect calorimetry (IC) and FE VO2 determinations were obtained. The Weir equation was used to calculate EE from the FE VO2 value. There was a strong correlation between the methods (r = 0.82, p less than 0.001). Mean EE by IC and FE was 2460 +/- 539 and 2372 +/- 787 kcal/day, respectively, a difference of 88 +/- 467 kcal/day. A single IC determination is often used to guide nutrition for several days. To evaluate this practice, FE and IC determinations were repeated in 8 patients. There was a 19% difference in EE between initial and follow-up IC, which was identical to the mean difference between paired FE and IC measurements. FE can be used to estimate EE, and is as accurate as using a single IC reading to predict EE on subsequent days. PMID- 1404519 TI - The disparity between hypothermic coagulopathy and clotting studies. AB - Hypothermic patients commonly develop coagulopathy, but the effects of hypothermia on coagulation remain unclear because clinical laboratories routinely perform clotting tests only at 37 degrees C. Measurements of activated partial thromboplastin times (APTT), prothrombin times (PT), and thrombin times (TT) were performed on plasma from normothermic and hypothermic rats at a range of temperatures (25 degrees-37 degrees C) to assess the effects of hypothermia on apparent clotting factor levels and clotting factor activities. In general, clotting times were more severely prolonged when test temperatures were hypothermic than when body temperatures were hypothermic. Indeed, little to no prolongation resulted from body hypothermia alone. These findings reveal the observed disparity between clinically evident hypothermic coagulopathy and near normal clotting studies. Clotting studies performed at 37 degrees C will not confirm hypothermic coagulopathy. These results indicate that the appropriate treatment for hypothermia-induced coagulopathy is rewarming rather than administration of clotting factors. PMID- 1404520 TI - The role of laparoscopy in abdominal trauma. AB - Thirty-nine hemodynamically stable trauma patients were evaluated prospectively by laparoscopy before planned celiotomy. Laparoscopy was performed using a forward-viewing laparoscope connected to two high-resolution video monitors. The mechanism of injury was blunt trauma in eight, stab wounds (SWs) in 16, and gunshot wounds (GSWs) in 15. Laparoscopy correctly identified the presence of an intraperitoneal injury in 26 patients. Six other patients had retroperitoneal injuries, five of which were seen on laparoscopy. The remaining seven patients had no demonstrable intraperitoneal or retroperitoneal injuries, did not undergo celiotomy, and were observed without morbidity. In comparison with findings at surgery, laparoscopy identified injuries to the liver in eight of ten, to the diaphragm in three of three, to the colon in two of three, to the stomach in three of three, to the kidney in one of one, to the spleen in none of three, and to the small bowel in none of four patients. Visualization of the spleen was achieved in only one patient. The extent of the hemoperitoneum was underestimated from the laparoscopic examination in all nine patients with greater than 750 mL of peritoneal blood, four of whom had undetected active bleeding. Laparoscopy was performed easily in all patients and there were no complications associated with its use. In conclusion, the absence of an intra-abdominal injury was correctly identified with laparoscopy in 11 patients and laparoscopy may decrease the need for celiotomy in selected patients. However, the inability to "run the small bowel," visualize the spleen, and evaluate hemorrhage limits the utility of laparoscopy in determining which patients with laparoscopically visualized injuries will require celiotomy. PMID- 1404522 TI - Monoethylglycinexylidide production parallels changes in hepatic blood flow and oxygen delivery in lung injury managed with positive end-expiratory pressure. AB - Mechanical ventilation with high levels of positive end-expiratory pressure (PEEP) decreases hepatic blood flow (HBF) and hepatic oxygen delivery (HO2D). Noninvasive methods of detecting decreased HBF might prevent hepatic ischemia and dysfunction. Monoethylglycinexylidide (MEGX) is a hepatic metabolite of lidocaine, used clinically to determine graft function following hepatic transplantation. In order to test the hypothesis that MEGX production would be affected by changes in hepatic hemodynamics associated with lung injury, 12 dogs were instrumented with femoral and pulmonary artery catheters. Splenectomy was performed and the portal and hepatic veins cannulated. The hepatic artery and portal vein were encircled with flow probes. Lung injury was induced in six animals (INJURED group) with oleic acid (0.08 mL/kg) and 10 cm H2O PEEP was added to correct subsequent shunt. Levels of MEGX were measured 15 minutes after injection of intravenous lidocaine (1 mg/kg). Levels of HBF, HO2D, and MEGX were measured at BASELINE, after lung injury (INJURY time point), and after addition of PEEP (PEEP time point). CONTROL animals (n = 6) were studied at the same time points but without lung injury or PEEP. Hepatic blood flow and hepatic oxygen delivery were significantly decreased after lung injury and further decreased after PEEP. Levels of MEGX were unchanged in the CONTROL group but were significantly reduced by lung injury and PEEP in the INJURED group. Decreased MEGX production may be a useful clinical indicator of reduced hepatic flow and oxygen supply in critical illness. PMID- 1404521 TI - An analysis of the relationship between fluid and sodium administration and intracranial pressure after head injury. AB - Severe head injury is the leading cause of traumatic death. When a severe head injury is combined with hypotension the mortality doubles. The use of asanguineous salt solutions to maintain blood pressure, however, may contribute to cerebral swelling and intracranial hypertension. For this reason, restrictions of fluids (FLD) and sodium (Na) have been advocated. To our knowledge, however, there are no clinical data to support this recommendation. We hypothesized that in adult patients sustaining severe head injuries (Glasgow Coma Scale score less than or equal to 8) with or without associated injuries: (1) FLD balance and total Na administered during the initial 72 hours of hospital admission are positively and significantly correlated with each other, and (2) total FLD, FLD balance, and total Na administration during the initial 72 hours are significantly and positively correlated with changes in ICP and adverse outcome. We retrospectively studied 40 adult trauma patients with severe head injuries. We found a significant correlation between total Na and FLD balance (R2 = 0.54; p less than 0.05). However, we found no significant correlation between total FLD and maximum ICP (R2 = 0.081), ICP score (R2 = 0.01), or outcome (R2 = 0.066), no significant correlation between FLD balance and maximum ICP (R2 = 0.000), ICP score (R2 = 0.000), or outcome (R2 = 0.01), and no significant correlation between total Na and maximum ICP (R2 = 0.000), ICP score (R2 = 0.001), or outcome (R2 = 0.02). We conclude that Na and FLD administration are not independent determinants of ICP during the initial 72 hours after brain injury. PMID- 1404523 TI - Thalamic hand: a late onset sequela of stroke and its influence on physical function after rehabilitation: two cases report. AB - Thalamic hemorrhage or infarction is one of the common causes of stroke. People who suffer from this type of cerebrovascular disease may develop thalamic syndrome which includes sensory disturbance, motor deficit and psychological problems. In this report, we introduce two cases of thalamic hemorrhage followed up for more than a half year after stroke. Delayed rigidity and choreodystonic type of involuntary movement over their paretic hand developed gradually. The metacarpophalangeal joints of the affected hand were kept flexed and the proximal and distal interphalangeal joints became extended. Thalamic hand is demonstrated in the appended pictures. Once the patient develops a thalamic hand, activities of daily living will be affected due to poor hand performance despite of high motor recovery stage. Early recognition and proper rehabilitation program for the patients with thalamic hand are emphasized. PMID- 1404524 TI - Traumatic tension pneumocephalus--intracerebral pneumatocele: a case report. AB - An 18-year-old Chinese man, suffering from head injury in a motorcycle accident, with right traumatic frontal intracerebral hemorrhage and frontal bone fractures, underwent emergency craniotomy with evacuation of hematoma at a local out-patient clinic and three months later, he suffered from CSF rhinorrhea. Headache, nausea and vomiting developed a week prior to admission. Tension pneumocephalus was diagnosed by computed tomography (CT) scan and plain skull X-ray. The fistula tract of the ethmoid sinus was investigated by radioisotope albumin (RISA) cisternography. The patient subsequently underwent emergency craniotomy for decompression. During the operation, we found that the intracerebral pneumatocele in the right frontal lobe communicated with the ipsilateral ethmoidal sinus, through which extracranial air ingressed and CSF egressed. This pneumatocele was unroofed and the fistula was temponaded by pericranial muscles and the Gelfomas sealed by tissue glue. Finally duraplasty was performed. Follow-up CT scan revealed that pneumocephalus subsided and the patient was cured of CSF rhinorrhea on discharge. As a surgical emergency, tension pneumocephalus can be successfully treated only by early diagnosis and early treatment. PMID- 1404525 TI - [Bleeding secondary duodenal diverticulum: a rare late complication following nephrolithotomy]. AB - Secondary duodenal diverticula are due primarily to traction upon that section from some other cause such as ulcer, cholecystitis and so forth. It accounts for 1.6 to 20% of all duodenal diverticula. Numerous reports of gastrointestinal hemorrhage from duodenal diverticula have appeared in the literature. But massive UGI bleeding due to secondary duodenal diverticulum, caused by nephrolithotomy, was a rare late complication. Here we present a case of a 63-year-old male patient who underwent a right side nephrolithotomy 10 and 8 years previously, then developed massive UGI bleeding suddenly. Pre-operative UGI series and gastroscopy showed chronic duodenal ulcer and duodenal diverticulum at second section where much blood clot was noted. In time, a successful operation was performed. This complication of secondary duodenal diverticulum was rare, so consideration regarding management and surgical approach was discussed. PMID- 1404526 TI - Intravenous dipyridamole technetium-99m MMI myocardial perfusion scintigraphy for detection of coronary artery disease. AB - To evaluate the efficacy of stress technetium-99m MMI (N-2-methoxy-2-methyl propyl isonitrile) myocardial perfusion scintigraphy (Tc-99m MMI) using intravenous dipyridamole for detection of coronary artery disease (CAD), we collected 66 cases (53 men, 13 women, aged 40-79 years old) between Sept. 1990 and Oct. 1991. The cases were divided into two groups: group I involving 44 patients received coronary arteriography (CAG) examination without previous percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG); group II embracing 22 patients received no CAG examination but all were suffering from old myocardial infarction (MI) evidenced by history and electrocardiography (ECG). All cases underwent Tc-99m MMI planar and single photon emission computed tomography (SPECT) both on intravenous dipyridamole stress and separate day rest tests. Of the 44 group I patients receiving both Tc 99m MMI and CAG, 35 (79.5%) were positive and 7 (16%) were negative by both tests and another 2 (4.5%) were positive by CAG only. Of those positive by both tests, 21 (60%) suffered from identical coronary arterial involvement, including 13 one vessel disease, 5 double-vessel disease and 3 triple-vessel disease. Of group II patients, 14 suffered from old inferior wall (IW) MI, 6 from old anterior or anteroseptal wall (AW) MI, 1 from old lateral wall (LW) MI and another 1 from combined old anterior and lateral wall (ALW) MI by ECG. Of the 14 patients with IWMI by ECG, all suffered from right coronary artery (RCA) disease but 7 (50%) of them from multivessel disease (MVD) by Tc-99m MMI. 5 of the 6 patients with AWMI by ECG suffered from left anterior descending coronary artery (LAD) disease, but 3 of them from MVD by Tc-99m MMI. Both patients with LWMI and ALWMI by ECG suffered from triple-vessel disease by Tc-99m MMI. The sensitivity of Tc-99m MMI in detecting CAD in group I was 95%, the specificity was 100%. The sensitivity for detection of individual coronary artery disease in LAD, left circumflex coronary artery (LCX) and RCA was 96%, 45% and 89% in this order and the respective specificity was 94%, 100% and 88%. In group II the sensitivity was 95%. The overall sensitivity of intravenous dipyridamole Tc-99m MMI for detection of CAD in groups I and II was 95%; specificity was 100% and accuracy was 95%. In conclusion, stress Tc-99m MMI using intravenous dipyridamole is a valuable method for evaluation and detection of CAD. PMID- 1404527 TI - Quantitative measurement of muscle and subcutaneous fat thickness in newborn by real-time ultrasonography: a useful method for site and depth evaluation in vaccination. AB - In order to quantify muscle thickness and choose the appropriate site for intramuscular injection of vaccines in neonates, we used ultrasonography to measure muscle and subcutaneous fat thickness of anterolateral mid-thigh, upper outer quadrant of buttock and middle area of deltoid in fifty full term (group 1) and thirty low birth weight (group 2) infants. A Hitachi EUB40 real-time scanner and a 5 MHz transducer was used in the study. We delineated the normal distribution of muscle and subcutaneous fat thickness in mid-thigh, buttock and deltoid areas of full term and low birth weight infants. There was no significant difference between male and female infants in the two groups. Muscle and subcutaneous fat thickness in the thigh area was 11.8 +/- 1.9 mm and 3.8 +/- 0.4 mm, respectively, in group 1; 8.6 +/- 1.7 mm and 2.7 +/- 0.5 mm in group 2. Figures in the buttock area were 10. 1 +/- 1.5 mm and 3.7 +/- 0.5 mm in group 1, 6.9 +/- 1.2 mm and 2.7 +/- 0.7 mm in group 2; and in the deltoid area were 5.2 +/ 0.7 mm and 3.4 +/- 1.5 mm in group 1 and 3.8 +/- 0.8 mm and 2.3 +/- 0.6 mm in group 2. There was significant logarithmic correlation between muscle thickness and body weight (r = 0.6, 0.8, 0.6) and muscle thickness and body length (r = 0.4, 0.6, 0.6) in thigh, buttock and deltoid areas of the low birth weight infants. In contrast, there was significant logarithmic correlation only between buttock muscle and body weight (r = 0.5) in the full term infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404528 TI - Reconstruction of the severely deficient acetabulum with the bipolar prosthesis and allo-autograft. AB - We reviewed the clinical results and radiographs of four patients who had revision of the acetabular component of a failed total hip arthroplasty with a bipolar socket supplemented by autoallograft to reconstruct massive bony defect. These patients were followed up from twelve to seventeen months. The clinical score was assessed by a modified d'Aubigne's rating score that assigned a maximum of 18 points. The preoperative clinical score ranged from 1 to 5 points (mean: 3.25 points). The postoperative score improved to a range of 13-17 points (mean: 15.25 points). Of the hips examined, nearly all were pain-free. The largest possible bipolar cup was used with solid structural allografting augmented by morseled cancellous autograft. These have been uniformly trouble-free with acetabular reconstitution. Cup migration was minimal or none. The follow-up periods were short and some migration is probably to be anticipated in the future. Although this technique was originally conceived as part of a staged procedure, it seemed as a definitive procedure yielding acceptable results for dealing with a severely deficient acetabulum. Larger series and longer periods of follow-up are demanded to support this assertion. PMID- 1404529 TI - [The management of sinus tracts of dental origin]. AB - The purpose of this study was to evaluate the results of conservative endodontic therapy of 86 fistulous cases of dental origin at the Department of Conservative Dentistry, Kaohsiung Medical College Hospital. Approximately 60% (52/86) endodontically treated teeth, with a minimum recall period of 6 months, were evaluated for success or failure. The results are as follows: (1) The overall success rate was 82.7% (43/52) fistulous cases. There was no significant statistical difference between male and female patients. (2) There was a better success rate with cases over a 2-year recall period than with cases under a 2 year recall period, but there was no significant statistical difference between these two groups. (3) Cases with periapical pathosis less than 5 mm in diameter, had a better success rate than those with periapical pathosis larger than 5 mm in diameter, but there was no significant statistical difference between these two groups. (4) There was a 79.1% (34/43) success rate in non-surgically treated cases, and a 66.7% success rate (6/9, excluding three successfully retreated cases which had been originally treated with a non-surgical technique) in surgically treated cases. PMID- 1404530 TI - [Histological study of the change of pulp tissue during shedding of the deciduous tooth]. AB - To understand the pulp change of root resorption of human deciduous teeth from a histological point of view, one hundred and twenty specimens were collected for study. The teeth (caries-free) were extracted for occlusal reason or because they exhibited various degrees of mobility and discomfort. The extent of root resorption was classified into five grades: Res. i, Res. 1/4, Res. 1/2, Res. 3/4 and Res. Co., according to Moorrees et al. and Haavikko. All teeth were fixed in 10% formalin (pH 7.2) immediately after extraction for 3-7 days. They were then decalcified for 14 days in 5% formic acid-sodium citrate, sectioned serially at 7 microns and stained with hematoxylin and eosin, Masson's stain, and silver impregnated stain. All sections were examined under a light microscope. The results obtained were as follows: 1. While the root was resorbed more than one half way, some normal pulp was replaced by the connective tissue as in inflammation. Internal resorption could be seen. 2. By the time deciduous root resorption was essential as complete, normal pulp tissue was no longer present. 3. Because the nerve degenerated during initial tooth resorption, there was no evidence that deciduous root resorption was under nervous control. 4. The present observation suggests that in addition to odontoclasts, several other cells such as fibroblast-like cells and macrophages, were actively involved in root resorption during the shedding of deciduous teeth. PMID- 1404532 TI - A possible role of heat shock proteins in human sperm motility. AB - The testicular spermatogenic stem and seminiferous tubular cells selectively synthesize heat shock proteins (Hsps) during heat stress. Hsps, synthesized from testicular cells and leukocytes, are identical in molecular masses as well as chemical properties. In this study, we induced the Hsps from leukocytes and investigated their in vitro effects on human sperm motility. Semen samples were divided into two parts, washed and unwashed. The whole blood was heated in 43 degrees C for 15 minutes for induction of Hsps. A trans-membrane migration method was used to examine the effect of heated blood plasma on human sperm motility. The main heat-induced proteins of leukocytes were detected by 2-D electrophoresis and Coomassie blue stain. Leukocytes treated by heat produced a large amount of Hsp72 and Hsp80, while only a small amount was observed in that of non-heated leukocytes. The heated blood plasma inhibited motility of washed sperm in a manner that was dose-dependent. In the presence of seminal plasma fluid, however, the inhibitory effects of heated plasma on human sperm motility could not be observed. It was concluded that the heat-induced substance(s) from leukocytes, which being highly possible the Hsps, interfered the mobility of wash human sperm and the inhibition might be antagonized by seminal plasma. PMID- 1404531 TI - Types of dementia in Taiwan--a prospective study. AB - We prospectively investigated 100 consecutive inpatients with suspected dementia to evaluate the relative frequency of various types of dementia in a general hospital of Taiwan. Dementia was confirmed in 86 cases (86%) according to the dementia criteria of the third revised edition of the Diagnostic and Statistical Manual of Mental Disorders and Clinical Dementia Rating Scale (greater than or equal to 1). In contrast to the western developed countries, vascular dementia (VD) (35%) was the leading type of dementia, followed by Alzheimer's disease (AD) (27%), mixed VD and AD (MIX) (14%), and other degenerative diseases (10%). Ten cases (11.6%) of potentially treatable dementia were identified and 8 of 10 had good improvement after appropriate treatment. There were significant age differences among patients with MIX, AD and VD (p less than 0.01). Those with MIX were the oldest (72.12 +/- 9.4) followed by AD (69.70 +/- 8.52) and VD (64.81 +/- 9.12). Males were slightly predominant in this series (male:female = 50:36). A comprehensive clinical investigation including laboratory tests, electroencephalography and CT are necessary in the assessment of demented patients in order to make correct etiological diagnoses which lead to appropriate treatment or management of this terrifying syndrome. PMID- 1404533 TI - Instrumented laxity test for the evaluation of posterior cruciate ligament reconstructed knee. AB - By making anterior and posterior drawer tests using "Laxity tester" is an objective way to evaluate the resting position of tibia plateau and knee laxity. This study followed up 16 cases of PCL reconstructed or pull-out repaired knees for an average of two years and seven months. A force of 20 1b was applied to evaluate knee laxity at 30 degree and 90 degree knee flexion. From paired t-test, the stability of reconstructed knees was not statistically different from that of control contralateral normal knees. The functional scores measured by the Gillquist scoring system for injured knees after reconstruction were satisfactory. Therefore the restabilized PCL deficient knees by the modified Clancy method or pull-out repair yielded good evaluation scores. The data of contralateral normal knee laxity obtained in this study was used as reference in pre-operative and post-operative evaluation of PCL injured knee. PMID- 1404534 TI - Intracranial meningioma. AB - Eighty-three patients with intracranial meningioma were retrospectively analyzed with regard to age, sex, anatomic location, mode of presentation and surgical outcome. The ages of the patients ranged from 11 to 77 years. Fifty-five (66%) were females and 28 (34%) were males. The peak incidence occurred between 40 and 49 years. The locations of the meningioma were as follows: 42.2% in the convexity, 15.7% in the parasagittal, 12.1% in the tuberculum sellae, 8.4% in the sphenoid ridge, and three cases with multiple lesions. Forty-two percent of our series were found to have hyperostosis of the skull bone. There were 7 cases with cyst formations found through computed tomography (CT). Histological classification showed 48.3% to be of meningothelimatous type, while 18.4% were of psammomatous type. One of the multiple meningiomas showed two different histological types. The degree of perifocal brain edema at CT scan was found to be related to the symptoms, the size of the tumor and seizure attack. Fifty-three out of 54 patients with episodes of seizures were found to have perifocal brain edema, whereas the histological features were less significant. Seventy-one tumors were treated by total resection and 16 tumors by subtotal resection. Follow-up study from 1 to 7 years showed the rate of recurrence in the total resection group to be 11.3%; in the subtotal resection group without radiation 42.9%, and in the subtotal resection group with radiation 66.7%. The over-all recurrence rate was 19.5% in our series. PMID- 1404535 TI - [Preparation and characterization of antibodies against Bungarus multicinctus venom by liposomes]. AB - Bungarus multicinctus venom was incorporated into sphingomyelin-cholesterol liposomes which were stabilized with osmium tetroxide. The lethal toxicity of B. multicinctus venom in osmicated liposomes greatly decreased to 1.03% that of crude venom. Rabbits were divided into four groups for immunization. Group A was immunized with crude venom, group B and group C with osmicated liposomes, and group D with osmicated liposomes followed by the crude venom. Immunization was performed in the presence of Freund's adjuvant except for group B. The antibody levels during the course of immunization were measured by ELISA and the contents of precipitating antibody were determined by quantitative precipitin reactions, while that of non-precipitating antibody was determined by affinity chromatography. Although the immune response was not increased by incorporating lipopolysaccharide immunostimulant, the specific neutralizing capacity of purified antibody from the pooled antisera of group D was more potent than that of the others. The almost non-toxic osmicated liposomes of B. multicinctus venom may be useful immunogens for the production of antiserum for treatment of snake bites. PMID- 1404536 TI - Central odontogenic fibroma of the mandible--a case report. AB - A 32-year-old male was referred to the Department of Oral and Maxillofacial Surgery, Kaohsiung Medical College Hospital, with the chief complaint of swelling in the region of the right mandibular angle. The histopathological examination confirmed the diagnosis of central odontogenic fibroma. A surgical enucleation with a surrounding bone trimming and an iliac bone graft was performed under general anesthesia. A three years follow-up showed good bone regeneration and no evidence of local recurrence. PMID- 1404537 TI - Splenic rupture as an infectious mononucleosis complication. AB - Splenic rupture is a rare yet serious complication associated with an infectious mononucleosis, especially in those patients with atypical clinical manifestations or those whose presentations are nonspecific or even completely asymptomatic. Since the death in these occasions is mostly attributed to acute massive hemorrhages, an early diagnosis and treatment is of paramount importance. This report illustrates that in infectious mononucleosis, one should be aware of the possibility of an unusual clinical presentation and the enlarged spleen may rupture spontaneously or by a causal traumatic force. White blood cell counts and their differentials at this catastrophic event may not be helpful in diagnosing infectious mononucleosis. PMID- 1404538 TI - A trial of adenosine for the termination of supraventricular tachycardia in infancy: a case report. AB - A 40-day-old male infant was admitted due to cough, anorexia and pale face. Rapid heart beat was found accidentally by auscultation. Electrocardiograms revealed supraventricular tachycardia (SVT) with a heart rate up to 250 beats per minute, and an absence of P waves. Intravenous bolus injection of 1 mg adenosine terminated the tachycardia, followed by transient complete atrioventricular block, then latent Wolff-Parkinson-White (WPW) syndrome with retrograde P waves. Adenosine may be a new trial for the termination of SVT, and also is a safe drug even in the presence of WPW syndrome. PMID- 1404539 TI - Thoracic manifestations of fungal diseases. PMID- 1404540 TI - Pathology of common pulmonary fungal infections. AB - The incidence of fungal pneumonias has increased dramatically since the 1960s, particularly in immunocompromised patients. Fungal infections may be divided into endemic and opportunistic varieties. In general, the truly pathogenic (endemic) fungi infect healthy individuals, and opportunistic fungi usually infect only immunocompromised hosts. Almost all common fungal infections are acquired by inhalation of contaminated soil, resulting in pulmonary infections. Once in the lungs, the fungi elicit tissue responses ranging from acute exudative reactions to granulomatous reactions. The pulmonary lesions may resolve, progress to a prolonged chronic course, or disseminate to other organs, resulting in systemic infections. The diagnosis of fungal infection depends on the demonstration of the organisms by culture or histology; serologic tests may confirm the diagnosis. Fungi in tissues can be identified by hematoxylin and eosin stains, but special stains such as Gomori's methenamine silver and periodic acid-Schiff reagent are often required for diagnosis. PMID- 1404541 TI - Clinical manifestations of pulmonary fungal infections. AB - Coccidioidomycosis, histoplasmosis, cryptococcosis, and blastomycosis are the most common deep pulmonary fungal infections encountered by the clinician. Each has a particular environmental habitat. As world travel increases, exposure to these infections becomes increasingly more common. The article reviews the microbiology, natural history, and clinical and laboratory findings of these diseases. Treatment options for these infections also are discussed. PMID- 1404542 TI - Pulmonary blastomycosis. AB - Pulmonary blastomycosis has a number of chest radiographic manifestations that may closely resemble those of tuberculosis, histoplasmosis, and other fungal diseases. Radiographic presentations of disease include airspace consolidation, nodular opacities, air bronchograms, masslike lesions, and military disease. Because the geographic distribution of blastomycosis overlaps that of histoplasmosis, distinguishing one from the other on the basis of the radiographic features may be difficult. In blastomycosis, the paucity of calcifications, lymphadenopathy, and cavitation is striking. The article reviews the clinical and radiologic features of blastomycosis and provides illustrative cases to enhance understanding of this disease. PMID- 1404543 TI - Pulmonary coccidioidomycosis. AB - Coccidioidomycosis is a fungal disease endemic in the southwestern desert area of the United States. The infection is acquired by inhalation of arthrospores, and 60% of the infections are asymptomatic. Chest radiographic abnormalities are common and may even be seen in asymptomatic cases. In patients with acute infection, segmental or lobar consolidation and nodular or patchy pulmonary opacities are frequent. Hilar and mediastinal adenopathy may be present in 20% of cases, usually with parenchymal findings. A small pleural effusion may occur in 20% of cases. Approximately 5% of patients with primary disease are left with chronic, residual lesions of the lung. These consist of nodules, cavities, pneumonia, adenopathy, pleural effusion, fibrosis, bronchiectasis, and calcification. Rarely, in about 0.5% of cases, the infection may disseminate to any organ. The chest radiograph demonstrates a miliary or reticulonodular pattern and mediastinal adenopathy. Overall the disease is benign in nature; but patients with severe, progressive pulmonary or disseminated disease often require medical and occasionally surgical management. PMID- 1404544 TI - Thoracic histoplasmosis. AB - Histoplasmosis is a fungal disease that is seen throughout the world. It is the most common systemic fungal infection in North America, and it is endemic in the Mississippi, Ohio, and St Lawrence River valleys. Its radiographic and clinical spectrum ranges from a totally self-limited disease with minimal or no radiographic findings to a rapidly progressive, disseminated, and sometimes fatal disease. The article discusses the various aspects of thoracic histoplasmosis with emphasis on the radiographic findings. PMID- 1404545 TI - Pulmonary cryptococcosis. AB - Cryptococcus neoformans is a ubiquitous soil fungus that rarely causes pneumonia in normal hosts but is a common cause of opportunistic infection. Pulmonary disease is initiated by inhalation of the organism, and a spectrum of radiographic manifestations can be seen. The most common finding is a poorly marginated nodule or mass. Lobar or segmental parenchymal opacities and, less commonly, a diffuse scattered nodular or reticulonodular pattern have also been observed. Associated adenopathy, pleural effusions, and cavitation are uncommon; when present, these are more common in immunocompromised patients. Establishing the diagnosis can be difficult, but pulmonary cryptococcosis should be considered in the differential diagnosis of patients in the proper clinical setting and with compatible radiographic findings. PMID- 1404546 TI - The spectrum of pulmonary aspergillosis. AB - Aspergillus species can produce a wide range of pulmonary disorders. Classically, pulmonary aspergillosis has been categorized into invasive, saprophytic, and allergic forms, all of which differ in their manifestations and therapy. More recently, however, other types of infection by this fungus have been recognized that do not fit into these traditional categories; an example is semi-invasive (chronic necrotizing) aspergillosis. In fact, these forms have features that are intermediate between those of the invasive and saprophytic types. The various types of aspergillosis can be regarded as constituting a continuous spectrum, ranging from invasive disease in the severely immunosuppressed patient to hypersensitivity reactions such as allergic bronchopulmonary aspergillosis (and bronchocentric granulomatosis) in the hyperreactive patient. Between these extremes are chronic necrotizing disease seen in midly immunocompromised hosts, and the noninvasive aspergilloma, which is due to saprophytic growth within a previously diseased area of lung in an otherwise normal host. Other intermediate forms may be encountered, their behavior being determined by the host immune status in combination with the underlying lung morphology. The radiographic and clinical features of these various forms of pulmonary aspergillosis are reviewed, including the more recently reported forms of infection such as Aspergillus tracheobronchitis and aspergillosis associated with acquired immunodeficiency syndrome and cystic fibrosis. The proposed concept of a disease spectrum is emphasized. PMID- 1404547 TI - Actinomycosis and nocardiosis of the lung. AB - Actinomyces and Nocardia species are frequently overlooked pulmonary pathogens until their presence is histologically proved. These infections often are not considered in the differential diagnosis of lung disease because of the spectrum of their presentation, the similarity of their appearance to other granulomatous or neoplastic diseases, and coexistence of these infections with other pulmonary conditions. Pulmonary actinomycosis is characterized by pulmonary consolidation, frequently with cavitation and spread to contiguous tissues without regard for normal anatomic barriers. The appearance often is confused with that of bronchogenic carcinoma or other granulomatous infections, especially tuberculosis. Pulmonary nocardiosis most frequently develops in immunocompromised patients, and the incidence of this infection is increasing. The radiographic manifestations of nocardiosis are pleomorphic, but early recognition is essential to initiate appropriate therapy. PMID- 1404548 TI - Pulmonary zygomycosis: a radiographic and clinical spectrum. AB - Eight documented cases of pulmonary zygomycosis were analyzed retrospectively with regard to radiographic and clinical features. Predisposing factors were diabetes mellitus in six cases, lymphoblastic lymphoma in one case, and surgery to correct a tracheoesophageal fistula in one case. Two of the patients with diabetes had also undergone renal transplantation for diabetic nephropathy and were immunosuppressed. The more usual radiographic findings of pulmonary zygomycosis represent a spectrum that comprises a normal chest radiograph, a lung abscess, subacute or chronic pneumonia that often evolves into a lung abscess, and rapidly progressive fatal pneumonia. Awareness of the various presentations of pulmonary zygomycosis is important because early diagnosis and appropriate therapy clearly have been shown to improve the survival rate of these patients. Zygomycosis should be included in the differential diagnosis when patients with diabetes mellitus, patients with leukemia or lymphoma, or immunocompromised patients present with or develop perplexing pulmonary abnormalities. PMID- 1404549 TI - Fungal infections of the chest in infants and children. AB - Although fungal infections of the thorax are often asymptomatic in children, fungi are capable of producing significant pulmonary and mediastinal disease in this population. Young infants and immunocompromised children are at increased risk for fungal infections and often develop disseminated disease. Pulmonary fungal infections present with a wide variety of findings, many of which are nonspecific. The article reviews the clinical and imaging characteristics of the more important fungal diseases that affect the thorax of infants and children. PMID- 1404550 TI - The use of diarrhoeal management counselling cards for community health volunteer training in Indonesia: the HealthCom Project. AB - The Indonesian Ministry of Health relies on a network of over a million kader (community health volunteers) to bring primary health care to the village level. In West Java, the Department of Health's Control of Diarrhoeal Disease (CDD) Program recently carried out an extensive research and development effort to produce effective job aids for the kader in CDD and a training programme to teach their use. A set of counselling cards was produced to provide kader with a tool to diagnose and treat diarrhoea and teach the proper use of ORS. Researchers conducted a controlled evaluation in which they measured the cards' effectiveness through observations of kader performance and interviews with mothers they had counselled. In the intervention group, 15 kader underwent two days training in the use of the cards when diagnosing and advising treatment for cases of diarrhoea in their villages. The 16 control kader received comparable CDD training without the cards. Each group provided lists of local mothers they pledged to counsel during the coming weeks. Follow-up interviews were held with these mothers to test their level of knowledge on CDD and to observe their ability to mix ORS properly. Significant performance differences between the intervention kader and mothers, and the control kader and mothers, were demonstrated. The intervention kader were consistently more accurate in their diagnoses and recommendations for treatment with a mean of 83% accuracy vs 68% for the control kader. Mothers counselled by the intervention kader also prepared ORS significantly better than the mothers counselled by the control kader, with 97 vs 74% accuracy. PMID- 1404551 TI - Influence of socioeconomic factors on the treatment and prevention of malaria in pregnant and non-pregnant adolescent girls in Nigeria. AB - The influence of socioeconomic factors on the treatment and prevention of malaria was investigated in 45 pregnant and a control group of 47 non-pregnant adolescent girls in the rural community of Imesi-Ile, Nigeria. The study consisted of focus group discussions and a house-to-house survey. During the survey, clinical and anthropometric measurements were taken of the girls and they were assisted in completing a prepared questionnaire which sought information on their methods of treatment and prevention of malaria. The results showed a higher incidence of malaria parasitaemia, anaemia and fever episodes in the group of pregnant adolescent girls. Both groups of girls use identical methods for the prevention of malaria but only a few pregnant girls as compared to non-pregnant girls receive modern hospital treatment for malaria. In particular, pregnant unmarried girls were less likely to receive antenatal care, to use the local health centres for the treatment of malaria and to adopt appropriate measures for the prevention of malaria. This trend was not due to aversion to hospital treatment since most people in the community prefer modern treatment of malaria to traditional or religious methods of treatment. The low utilization of hospital treatment by the pregnant girls was found to be due to perceived high cost of treatment at the health centres and to lack of privacy. We conclude that a malaria treatment service that utilizes modern methods and is both cheap and confidential will be preferred by pregnant adolescent girls in Imesi-Ile. PMID- 1404552 TI - Enterotoxigenic drug resistant plasmids in animal isolates of Escherichia coli and their zoonotic importance. AB - A study was undertaken to determine how widely drug resistant enterotoxigenic plasmids are distributed among the animal isolates of Escherichia coli, and their potential for exchange. Thirty-one strains of E. coli isolated from metritis, septicaemia and diarrhoea of animals were tested for the production of enterotoxins. Thirteen strains were enterotoxin producers. Five produced heat stable enterotoxins (ST), four heat-labile (LT) and four strains produced both (LT/ST) types of enterotoxins. Most of the enterotoxin producing E. coli strains were isolated from diarrhoeal sources, followed by septicaemia and metritis. Of the 13 enterotoxigenic E. coli, nine were resistant to various antibiotics which transferred their drug resistance partially or completely into an E. coli K-12 recipient. Only one strain of serogroup 032, isolated from equine metritis, transferred ampicillin, oxytetracycline and doxycycline resistance and heat labile enterotoxin biosynthesis determinants en bloc. Plasmid DNA analysis of the exconjugants showed the presence of a 41.8 MDa conjugative plasmid. The presence of such autotransferable enterotoxin biosynthesis replicons in their unusual ecological niches such as metritis and septicaemia suggests the ubiquitous nature of enterotoxin genes which perhaps were selected and spread due to the presence of genes for drug resistance. The potential of cross-infection of human beings from animals and vice versa via such plasmids is discussed. PMID- 1404553 TI - Experimental infection of dogs with a Zimbabwean strain of Rickettsia conorii. AB - Seroconversion was demonstrated in dogs artificially infected with a Zimbabwean strain of Rickettsia conorii. No haematological or biochemical abnormalities were found and the only clinical signs observed were pain, erythema and oedema at the inoculation site and regional lymphadenopathy. Intermittent rickettsaemia was detected using the centrifugation shell vial technique up to 10 days post inoculation. PMID- 1404554 TI - The laboratory diagnosis of rickettsial diseases in Hong Kong. AB - Indirect immunoperoxidase (IP) tests against antigens of Rickettsia typhi, R. sibirica and R. tsutsugamushi were carried out on serum samples from 10 patients known to have high titres against one or more Proteus OX antigens in the Weil Felix (WF) test. The IP test confirmed rickettsial infection in nine of the 10 patients, giving unequivocal indications of the grouping of the infecting Rickettsia species and, in one instance, showing a diagnostic IgM titre in a specimen taken on day 3 of the patient's illness. IP tests confirmed four cases of spotted fever group rickettsial infection, three cases of urban or murine typhus and two of scrub typhus. PMID- 1404555 TI - Visceral leishmaniasis with cysticercosis. AB - A chest wall nodule in a boy with relapsed proven kala-azar was found to contain a cysticercus. In the fibrous wall with lymphohistiocytic aggregates were mononuclear phagocytes containing amastigotes of L. donovani. PMID- 1404556 TI - Laboratory studies on Yersinia pestis during the 1991 outbreak of plague in Lushoto, Tanzania. AB - Thirty-one specimens from patients involved in an outbreak of plague were cultured. Suspicious isolates were presumptively identified by colonial characteristics, simple strains and by API 20E, and confirmed by inoculation into white mice. Antimicrobial susceptibility testing was also done. The isolation rate of Y. pestis was 22.6%. All isolates were uniformly sensitive to tetracycline, streptomycin, sulphadimidine and chloramphenicol; moderately sensitive to erythromycin, and resistant to trimethoprim. Y. pestis was confirmed as a cause of the epidemic and sensitivity of Y. pestis to the four antimicrobial agents used was demonstrated. It is recommended that laboratories in zonal hospitals serving areas with plague foci should be provided with facilities for isolation and preliminary identification of Y. pestis in order to speed up diagnosis of plague outbreaks. Confirmation of the identity, biotyping and antibiotic susceptibility testing should be undertaken in a well established national reference laboratory. This appears to be the first publication on bacteriological investigations of human plague in Tanzania. PMID- 1404557 TI - Enteropathogenic Escherichia coli as a cause of diarrhoea among children in Singapore. AB - Enteropathogenic Escherichia coli (EPEC) was isolated from 2.7% of 2983 children under 3 years of age with diarrhoea in Singapore. Of the nine serotypes identified, the most common were 0126:K71(B16), 086:K61(B7) and 0127:K63(B8). Infants were at the greatest risk of contracting gastroenteritis due to EPEC, and female children were slightly more susceptible than males. Antimicrobial susceptibility tests showed that the EPEC strains were generally resistant to ampicillin, streptomycin, tetracycline and triple sulpha, but highly sensitive to ceftriaxone and gentamicin. PMID- 1404558 TI - Caesarean sections in developing and developed countries. AB - A clinical study of 1086 cases of caesareans done in the period 1987-1991 in a rural institute is presented with a review of the latest data from India and elsewhere. Of the women, 86.19% were between 20 and 30 years; 43.83% were primigravidas. The most common indications were obstructed labour and malpresentations. 17.76% of the emergency and 14.64% of registered obstetric admissions resulted in caesarean delivery. The status of caesarean births is very different in developed and developing countries though both face the problem of its very high incidence. PMID- 1404559 TI - Human infection by Phagicola sp. (Trematoda, Heterophyidae) in the municipality of Registro, Sao Paulo State, Brazil. AB - In 1988, nine cases of human parasitism by Phagicola sp. were diagnosed in the municipality of Registro (Sao Paulo State, Brazil) by stool examinations, in patients who ate raw mullet (Mugil sp.). Six (66%) of the nine patients suffered from flatulence and four (44%) had diarrhoeal episodes; six (66%) showed slight eosinophilia. On the same occasion, 61 dogs and 11 cats from Registro were also submitted to stool examination. Only one dog (1.6%) showed Phagicola eggs in the stool. All patients were treated with a single dose of praziquantel (50 mg kg-1 body weight) and control stool tests performed on the 15th, 30th and 60th days post-treatment showed no trematode eggs. PMID- 1404560 TI - Acute intravascular haemolysis in Vanuatu following a single dose of primaquine in individuals with glucose-6-phosphate dehydrogenase deficiency. PMID- 1404561 TI - Intestinal obstruction due to Taenia saginata infection: a case report. AB - Surgical complications of Taenia saginata infection, the bovine tapeworm which man acquires by eating undercooked beef, are mentioned in standard texts; however, none of these seem to give any specific reference. Reported here is one case of acute mechanical intestinal obstruction due to a bolus impaction of Taenia saginata at the level of the ileocaecal valve. The rarity of this clinical presentation as well as the probable mechanism of obstruction are discussed. PMID- 1404562 TI - Chronic diarrhoea due to strongyloidiasis in a Nigerian with chronic renal failure: a case report. AB - A case of chronic diarrhoea due to infection with Strongyloides stercoralis in a Nigerian patient with chronic renal failure is presented. Due to the potential for fatal outcome in this infection, strongyloidiasis should be kept in mind as a cause of chronic diarrhoea in chronic renal failure patients in endemic areas. PMID- 1404563 TI - Typhoid fever and nephrotic syndrome--an unusual association. AB - We report a case of nephrotic syndrome seen in a 9-year-old boy having a significant temporal relationship with culture proven multidrug resistant Salmonella typhi infection. Such an association is quite unusual and probably has not been reported before. PMID- 1404565 TI - Necrotizing cervical fasciitis of unknown origin. AB - Necrotizing fasciitis is an acute soft-tissue infection rarely seen in the head and neck area. The case of a 29-year-old female with necrotizing cervical fasciitis of unknown origin is presented. These infections usually result from dental infections; this patient, however, denied any associated dental problems. The patient presented with an erythematous swelling over the anterior neck associated with a choking sensation and an elevated WBC suggestive of acute thyroiditis. After three days of hospitalization the skin over the anterior neck area became necrotic. Surgical debridement of the area was undertaken with significant improvement. Once wound healing had commenced a pedicled flap was used to reconstruct the large defect. Flap selection for closure of the defect is discussed. It is apparent that early recognition and surgical debridement of necrotizing fasciitis is vital to ensure a rapid recovery. PMID- 1404564 TI - Management of substernal goitre. AB - Goitres of the thyroid gland whose major component resides substernally would appear to have a different presentation and management protocol than those goitres that reside mainly in the neck. These goitres, as opposed to their supraclavicular counterparts, usually present with symptoms referrable to compression of the trachea or esophagus. Even in those patients who are asymptomatic, a precise history may elicit pertinent findings. Furthermore, these goitres do not respond to suppression and require surgical removal. The trans cervical approach is the most desirable, but the surgeon must be willing to enter the chest on that rare occasion. We reviewed the charts of 938 patients undergoing thyroid surgery who were registered in the Head and Neck Tumour Registry of the University of Toronto. Approximately 2.4% of patients had substernal goitres. Their history, pathology and ultimate surgical management will be discussed. PMID- 1404566 TI - Congenital fistula of the apex of the pyriform sinus: an overlooked phenomenon of debatable origin. AB - Fistula of the pyriform sinus apex is an often overlooked entity which generally manifests itself as acute suppurative thyroiditis or recurrent deep neck abscesses in children or young adults. Two cases are reported. Arguments in favor of a fourth pharyngeal pouch origin are stressed and the surgical management is described. PMID- 1404567 TI - Hemangioma of the masseter muscle. AB - Intramuscular hemangiomas are rare benign tumors of vascular origin. The masseter is the muscle most commonly involved in the head and neck. A case of intramuscular masseter hemangioma is presented, the literature reviewed, and appropriate diagnostic modalities discussed. PMID- 1404568 TI - Malignant melanoma of the upper respiratory tract and the oral cavity. AB - Twenty-six patients with mucosal malignant melanoma of the upper respiratory tract and of the oral cavity were seen at the oncologic departments of eastern Denmark from 1955 to 1989. There were 17 males and nine females with an average age of 65 years. Primary symptoms lasted from one to 24 months and depended on localization of tumor. Five patients had lymph node metastases at the time of diagnosis; one also had distant metastases. Ten patients had surgery as primary treatment, 10 had combined surgery and radiotherapy and six had radiotherapy. Complete remission after primary treatment was seen in 22 cases (85%) and lasted from three to 94 months. Seventeen patients had recurrence, six of these had recurrence twice or three times. The five-year crude survival was 35% and only one patient (4%) lived more than 10 years. Recurrence-free survival among the 22 patients with initially complete response was 14%. PMID- 1404569 TI - Extracranial head and neck schwannomas. AB - Extracranial head and neck schwannomas are usually benign and rarely malignant tumors of peripheral nerve sheath origin. The clinical presentation of these tumors is reviewed in our series of 21 patients, emphasizing the diagnosis with dynamic infused CT scans. Management is suggested and outcome analysis is provided. PMID- 1404570 TI - The importance of nasal resistance in obstructive sleep apnea syndrome. AB - The importance of nasal airflow resistance in the pathogenesis of obstructive sleep apnea syndrome (OSAS) remains contentious. We performed formal nocturnal polysomnography (PSG) on OSAS patients under conditions of baseline and reduced nasal resistance to answer two main questions. First, to what degree does baseline nasal airflow resistance influence upper airway collapse in OSAS patients? Second, in what proportion of the OSAS population is baseline nasal resistance contributing to the pathogenesis of upper airway collapse? Our study group consisted of 10 patients with a wide range of OSAS severity. Six of these patients had symptoms and clinical evidence of chronic nasal obstruction which, in some, was associated with markedly elevated nasal resistance. A placebo (normal saline) was instilled in the nose of each patient on the night of baseline data collection. On the treatment night of the study, nasal resistance was reduced by application of topical vasoconstrictor and insertion of vestibular stents designed to dilate the area of the nasal valve. Posterior rhinomanometry was used to measure resistance to nasal airflow immediately before and after each PSG study. Although treatment was associated with a subjective improvement in sleep quality and mean drop in nasal resistance of 73% (P less than 0.001), there was no significant improvement in sleep architecture, nocturnal oxygenation, or the amount of apnea experienced by patients. The most significant improvement was a reduced number of arousals/hour from 52.4 +/- 12.4 on placebo to 43.7 +/- 10.2 on treatment (P less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404571 TI - Oncocytoma presenting as a choanal polyp: a case report. AB - Oncocytomas account for less than 1% of all salivary gland neoplasms. Histochemical methods and electron microscopy showing the large amount of characteristic mitochondria have made the definition of the tumor more precise. A solid oncocytoma originating in the nose and presenting as a choanal polyp is described. Pre- and postoperative CT scans are shown as light and electron microscopy photomicrographs. The tumor had no invasive or other malignant characteristics and was therefore classified as a benign oncocytoma. PMID- 1404572 TI - Stromal calcification in choanal polyp. AB - A 50-year-old man, presenting with headache, was suspected of having a malignant nasopharyngeal tumor on the basis of his CT results. A CT scan revealed diffuse calcification in a large nasopharyngeal polyp. Xeroradiography of the specimen demonstrated the calcifications to extend centrally along the stroma. The histology and the radiologic features of this choanal polyp, resulting from diffuse central calcification of the stroma, are a unique feature that might mimic malignancy. PMID- 1404573 TI - Is head-shaking nystagmus a sign of vestibular dysfunction? AB - It has been proposed that head-shaking nystagmus is a reliable test or indicator of vestibular dysfunction. Using a series of 340 patients and 20 controls, this paper compares the vestibular test data to head-shake test data to answer some of the questions about this poorly understood response. Head-shaking nystagmus appears to reflect the underlying spontaneous nystagmus and its direction has no relationship to the side of the vestibular asymmetry. PMID- 1404574 TI - Electrocochleographic recordings in chronic and healed perilymphatic fistula. AB - This study examined electrocochleographic recordings in 15 guinea pigs with perilymphatic fistulas. A chronic round window fistula was induced in each animal by insertion of a sigmoid stainless steel needle with the lumen intact. In the contralateral control ear, a similar needle was inserted with the lumen crushed. In this way the model compared acute (control group) versus chronic (experimental group) perilymphatic fisulae. Electrocochleographic recordings were obtained before, immediately after needle insertion, in a subset at two to three weeks after needle insertion, and again at 17-22 weeks when the fistulas had healed with the needles still in place. Minimal threshold changes were noted from the pre- to the acute post-condition. More marked elevation of threshold was noted for the 17-22 weeks condition. Threshold elevation was greater in the experimental ears but was present in the control ears. The SP/AP amplitude ratio was generally stable for the pre- to post-conditions in both ears. For the 17-22 week epoch the SP/AP amplitude ratio was still fairly stable for the click stimulus but the ratio diminished for the toneburst stimuli. For the subset analyzed at 7-21 days the SP/AP amplitude ratio tended to increase for both groups for all stimuli although AP thresholds were normal. PMID- 1404575 TI - Gore-Tex implant as tissue filler in cheek-lip groove rejuvenation. AB - The cheek-lip grooves, often referred to as nasolabial folds, are one of the facial characteristics most commonly complained about by patients in all age groups. A variety of methods for correction have been proposed, using implants or autografts. Some of the methods have relied on diminishing the crest lateral to the groove thus camouflaging the depth of the cheek-lip fold. These procedures have proven to be of limited effect, either because of the amount of correction obtained or because they are short-lasting. The Gore-Tex implant proved its safety and biocompatibility over the past decade as a vascular graft. The characteristics of this implant material are described and compared to other commonly used synthetic implants. A surgical technique of applying the Gore-Tex soft tissue patch in facial aesthetic surgery, particularly in cheek-lip rejuvenation, is presented. This technique has been applied in 17 consecutive patients for the correction of prominent cheek-lip grooves with a follow-up period of eight months. Results showed satisfactory improvement without significant complications. PMID- 1404576 TI - Colored cocaine. PMID- 1404577 TI - Otitis media and CNS complications. AB - Intracranial complications from otitis media can be quite devastating to the patient if an early diagnosis is not made. Patients may develop meningitis, venous sinus thrombosis or cranial nerve palsies, as well as intracranial abscess. The presenting features in such cases may be subtle and include headache, nausea, vomiting, personality changes and signs of increased intracranial pressure as well as focal neurological deficits. A case of intracranial brain abscess is presented in a patient with a history of chronic otitis media with cholesteatoma. Delay in the diagnosis of intracranial complications of otitis media can lead to improper treatment with increased morbidity and mortality. The etiology and treatment of complications affecting the CNS is discussed. PMID- 1404578 TI - Deafness, dysphagia and a middle ear mass in a patient with neurofibromatosis type 2. PMID- 1404579 TI - Longitudinal evaluation of uterine myoma growth during pregnancy. A sonographic study. AB - Thirty-six pregnant women with a single uterine myoma were examined by ultrasonography at 2 to 4 week intervals. The initial diagnosis was made in 12 patients before pregnancy and in the other 24 patients between 9 and 12 weeks of gestation. Thirty-four women had a scan 4 weeks after delivery. A reduction in size was observed in puerperium, which may indicate a return to its initial volume. Myoma growth was analyzed in different periods of gestation. An increase in volume during pregnancy was observed in 31.6% of cases. A statistically significant change in volume was noted between the first and the third trimesters (P < 0.001). The greatest increase in volume of myomas occurred before the 10th week of gestation. The relationship between myoma volume and myoma growth in the different gestational periods considered was not statistically significant. On the other hand, when myoma volume was related to complications during pregnancy or at delivery, a statistically significant difference was observed. Myomas with volumes greater than 200 cm3 show a higher rate of complications than those with volumes equal to or less than 100 cm3. PMID- 1404580 TI - Effect of verapamil on portal blood flow in patients with liver cirrhosis. AB - The effect of acute (80 mg orally) and prolonged (240 mg orally daily for 2 weeks) verapamil administration on portal blood flow was studied in 12 patients with histologically proved alcoholic liver cirrhosis. Portal hemodynamics were examined by the ultrasonic duplex Doppler system. Thirty minutes after acute verapamil administration, the following parameters remained unchanged: (1) cross sectional area of the portal vein, from 1.52 +/- 0.41 to 1.51 +/- 0.43 cm2; (2) portal blood velocity, from 13.2 +/- 1.6 to 13.4 +/- 1.6 cm/s; (3) estimated volume of portal blood flow, from 931 +/- 96 to 954 +/- 103 mL/min; and (4) congestion index of the portal vein, from 15.1 +/- 8.3 to 15.6 +/- 8.8 cm, respectively (P = > 0.05). In addition, no significant changes in portal blood hemodynamics were noted after prolonged verapamil administration (P > 0.05). These results demonstrated that verapamil did not alter portal blood flow in patients with alcoholic liver cirrhosis. PMID- 1404581 TI - An unusual sonographic appearance: the pyramidal gallstone. PMID- 1404582 TI - Various sonographic patterns of smooth muscle tumors of the gastrointestinal tract: a comparison with computed tomography. AB - To evaluate the sonographic patterns of smooth muscle tumors of the gastrointestinal tract, we analyzed 25 patients with histologically confirmed smooth muscle tumors. Sonography revealed no abdominal mass in seven patients (sonogram-negative), and abdominal masses in 18 patients (sonogram-positive). The mean size of tumors in the sonogram-negative group (4.5 +/- 1.5 cm) was smaller than that in the sonogram-positive group (11.4 +/- 3.5 cm). We classified the various sonograms into three patterns. Comparing the sonograms with the computed tomographic pictures of each pattern, we theorized that the different patterns on sonograms may be caused by tumor necroses of different sizes with or without gas in the necrotic cavity. For the necrotic tumors, the size of the necrotic area did not correspond to the size of the tumor. However, the tumors with necroses were significantly larger than those without necroses. A central necrosis was found in cases exhibiting both leiomyosarcoma and leiomyoma. On comparing the sonogram-positive and sonogram-negative groups, we found that the size and location of a tumor may affect the detection rate of that tumor by sonography. PMID- 1404583 TI - The "lying down" adrenal sign: a sonographic indicator of renal agenesis or ectopia in fetuses and neonates. AB - An inability to image the kidneys, severe oligohydramnios, and an empty (nonvisualized) urinary bladder are the most common sonographic findings in fetuses with renal agenesis. The same features, except for the oligohydramnios, are seen in neonates with renal agenesis. Failure to visualize a kidney in the usual flank location with or without demonstration of the kidney in an ectopic location may also be a feature in fetuses or neonates with renal ectopia. The adrenal gland has an unusual but distinctive appearance on longitudinal sonograms in these patients. Sonograms of 23 fetuses and six neonates referred for presumed bilateral or unilateral renal agenesis or ectopia were reviewed retrospectively for the presence of a flattened ("lying down") adrenal gland. At the time of the examination, the adrenal gland was not actively sought as a part of the fetal survey or postnatal examination but was found retrospectively in 48% of these subjects. Although this finding has been described previously, the emphasis was on this observation as a potentially confusing sonographic feature. This manuscript emphasizes the characteristic appearance of the adrenal gland which instead serves as a simple means of confirming that the kidney did not develop in the flank. Detection of a flattened ("lying down") adrenal gland is an observation that should be actively sought in all fetuses and neonates with a presumed diagnosis of renal agenesis or ectopia. PMID- 1404584 TI - Doppler flow velocity waveforms in fetal surveillance of twins: a prospective longitudinal study. AB - In 37 consecutive twin pregnancies, monthly Doppler sonographic measurements were made of blood flow velocity waveforms of the internal carotid and umbilical artery of each fetus. A total of 197 Doppler studies were performed. Of the 74 infants, 23 were small for gestational age (SGA). Thirty-five of the SGA Doppler studies were abnormal, giving an overall sensitivity for predicting SGA fetus of 58% and a positive predictive value of 71%. These data are not as sensitive and specific as our earlier data; however, Doppler criteria preceded sonographic diagnosis of SGA by a mean interval of 3.7 weeks and demonstrated better sensitivity and specificity. A combination of these parameters improves sensitivity to 84%. We conclude that Doppler velocimetry complements real-time ultrasonography for the early diagnosis of abnormal growth in twin pregnancies. PMID- 1404585 TI - Color Doppler sonography in the evaluation of the adult acute scrotum. AB - Color Doppler sonography (CDS) was used to evaluate 35 adult males with acute scrotal discomfort. Correlative nuclear scintigraphy was performed in 15 patients. Surgical correlation was available in 10 patients with clinical follow up in the remaining 25. The complete absence of intratesticular color flow was used as our criterion for testicular ischemia. This was found to be 100% sensitive and 100% specific in 8 patients with surgically confirmed testicular ischemia. Spontaneous detorsion was noted in one patient with hyperemia demonstrated by color imaging. Increased color flow was found in 20 patients with the clinical impression of scrotal inflammation. Nuclear scintigraphy and color Doppler imaging had 100% agreement in 15 patients. Color Doppler sonography is a useful and highly accurate diagnostic method in the evaluation of patients with the acute scrotal syndrome. Color flow imaging is comparable to nuclear scintigraphy in the diagnosis of testicular ischemia. PMID- 1404586 TI - Lipoblastoma: diagnosis with computed tomography, ultrasonography, and color Doppler imaging. PMID- 1404587 TI - Color Doppler flow imaging of hepatic focal nodular hyperplasia. PMID- 1404588 TI - Prenatal sonographic diagnosis of a pontine lipoma. PMID- 1404589 TI - Sonographic recognition of unilateral megalencephaly. PMID- 1404590 TI - Spontaneous resolution of a sonographically complicated fetal ovarian cyst. PMID- 1404591 TI - Cap-independent translation by the 5' untranslated region of Theiler's murine encephalomyelitis virus. AB - The RNA genome of Theiler's murine encephalomyelitis viruses, a picornavirus belonging to the genus Cardiovirus, is translated in infected cells to a polyprotein. Unlike cellular messages, the 5' end of the RNA is not capped, and the untranslated region (UTR) is quite long (1,064 nucleotides in size). In poliovirus and encephalomyocarditis virus, the 5'UTR is thought to mediate cap independent translation. We report here experiments to determine the role of the Theiler's murine encephalomyelitis virus 5'UTR in translation. Recombinant DNAs were constructed that were transcribed into bicistronic mRNAs encoding 5' chloramphenicol acetyltransferase intercistronic sequences linked to luciferase and a poly(A) 3' tail. The sequences of the 5'UTR, either complete or with sequential 5' deletions, were inserted into the intercistronic region. Bicistronic RNA transcripts were translated in a rabbit reticulocyte lysate or used to transfect BHK-21 cells, and chloramphenicol acetyltransferase and luciferase synthesis was quantitated. The results strongly suggest that the Theiler's virus 5'UTR promotes cap-independent translation and that the 5' boundary of the relevant signals resides 3' to nucleotide 500. Monocistronic mRNAs were synthesized by using an expression vector in which the 5'UTR containing deletions at the 3' terminus was inserted 5' to the coding sequences for luciferase. Analysis of luciferase translation in a rabbit reticulocyte lysate suggests that the 3' end of the translation initiation signal lies between nucleotides 1043 and 1053. PMID- 1404592 TI - Antioxidants selectively suppress activation of NF-kappa B by human T-cell leukemia virus type I Tax protein. AB - Oxygen radical scavengers, such as dithiocarbamates and cysteine derivatives, inhibit activation of the ubiquitous transcription factor nuclear factor kappa B (NF-kappa B) after treatment of cells with tumor necrosis factor, phorbol ester, and interleukin-1. An involvement of oxygen radicals was more directly evident from the induction of NF-kappa B by low concentrations of H2O2 and the demonstration that cells stimulated with various NF-kappa B inducers release H2O2 and superoxide. In this study, we used the antioxidant pyrrolidine dithiocarbamate (PDTC) to investigate whether the activation of NF-kappa B by the viral transactivator Tax from human T-cell leukemia virus type I also depends on the production of reactive oxygen intermediates. The Tax-induced activation of the DNA-binding activity of NF-kappa B in Jurkat T cells was potently suppressed by micromolar concentrations of PDTC. Within the same concentration range, PDTC and two other dithiocarbamates also strongly interfered with transactivation of the long terminal repeat (LTR) of human immunodeficiency virus type 1 by Tax but had no effect on transactivation of the same LTR by Tat. Transactivation of the human T-cell leukemia virus type I LTR by Tax was also barely influenced. Tax seems to activate NF-kappa B by a mechanism shared with all other inducers of NF kappa B tested so far. It appears that one of the pleiotropic activities of Tax leads to an enhanced production of oxygen radicals that are required for activation of NF-kappa B. PMID- 1404593 TI - Interference is controlled by segment 2 and possibly by segment 8 of the nondefective interfering influenza virus variant A/FM/1/47-MA. AB - On mouse adaption of A/FM/1/47, a variant, A/FM/1/47-MA (FM-MA), that had acquired the properties of increased virulence and interference was produced. Coinfection of cells with FM-MA and prototype strains of influenza virus yielded > 100-fold more FM-MA virus than prototype virus, whereas coinfection with the same prototype strains and the parental A/FM/1/47 virus produced equivalent yields, indicating that FM-MA had acquired mutations that confer the property of interference during mouse adaption. FM-MA is a nondefective interfering virus that grows to a high titer in vivo and in vitro. It has previously been shown that segments 4, 7, and 8 and possibly segment 5 account for the increased virulence. In this study we show by genetic analysis of FM-MA x A/HK/1/68 reassortants that segment 2, coding for the polymerase-associated protein PB1, and possibly segment 8, encoding the NS1 and NS2 proteins, control the ability of FM-MA to interfere. Interference could not be overcome by increasing the titer of the coinfecting strain, but delaying FM-MA infection by 4 to 6 h did avoid interference. During interference of A/HK/1/68, protein synthesis was inhibited by less than 65% throughout coinfection. Given the kinetics of interference and the small perturbation in protein synthesis, interference appeared to occur at the level of late genome replication or virus assembly. Virulence and interference in FM-MA were not linked. An interfering avirulent FM-MA x A/HK/1/68 reassortant, E07, was capable of protecting mice against lethal pneumonia due to a virulent noninterfering reassortant, H04. PMID- 1404594 TI - Brome mosaic virus RNA replication proteins 1a and 2a from a complex in vitro. AB - Brome mosaic virus (BMV) is a positive-strand RNA virus that encodes two RNA replication proteins, the helicaselike 1a and the polymeraselike 2a. 1a and 2a share extensive sequence similarities with proteins encoded by many other members of the alphaviruslike superfamily. While further purifying enzymatically active RNA-dependent RNA polymerase from plants infected by BMV, we observed that 1a, 2a, and the polymerase activity all cofractionated through multiple independent purification steps. Moreover, using immunoprecipitation, we found that BMV 1a and 2a proteins synthesized in rabbit reticulocyte lysates or insect cells can form a specific complex in vitro. Complex formation was more efficient when 1a and 2a were cotranslated than when they were mixed after independent synthesis. In an antibody-independent assay, in vitro-translated 1a protein was also found to bind to 2a protein fixed on a nylon membrane. A three-amino-acid insertion in 1a that blocks BMV RNA replication in vivo also blocked in vitro interaction with 2a, while another two-amino-acid insertion that renders the 1a protein temperature sensitive for RNA replication interacted in vitro with 2a at 24 degrees C but not at 32 degrees C. These results and previous genetic data suggest that the 1a-2a interaction observed in vitro is required for BMV RNA replication and may have direct implications for other members of the alphaviruslike superfamily. PMID- 1404595 TI - Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro. AB - We have probed the structural organization of the human immunodeficiency virus type 1 integrase protein by limited proteolysis and the functional organization by site-directed mutagenesis of selected amino acid residues. A central region of the protein was relatively resistant to proteolysis. Proteins with altered amino acids in this region, or in the N-terminal part of the protein that includes a putative zinc-binding motif, were purified and assayed for 3' processing, DNA strand transfer, and disintegration activities in vitro. In general, these mutations had parallel effects on 3' processing and DNA strand transfer, suggesting that integrase may utilize a single active site for both reactions. The only proteins that were completely inactive in all three assays contained mutations at conserved amino acids in the central region, suggesting that this part of the protein may be involved in catalysis. In contrast, none of the mutations in the N-terminal region resulted in a protein that was inactive in all three assays, suggesting that this part of integrase may not be essential for catalysis. The disintegration reaction was particularly insensitive to these amino acid substitutions, indicating that some function that is important for 3' processing and DNA strand transfer may be dispensable for disintegration. PMID- 1404596 TI - Mammalian subtilisin-related proteinases in cleavage activation of the paramyxovirus fusion glycoprotein: superiority of furin/PACE to PC2 or PC1/PC3. AB - The fusion glycoprotein precursor of Newcastle disease virus is ubiquitously cleaved in the constitutive secretory pathway if it possesses an oligobasic cleavage motif (RRQR/KR), whereas the precursor is refractory to cleavage if the motif is monobasic (GR/KQGR). We examined the cleavage activity of the mammalian subtilisin-related proteinases furin/PACE, PC2, and PC1/PC3, which are thought to be responsible for proprotein processing in either the constitutive (furin/PACE) or the regulated (PC2 and PC1/PC3) secretory pathway, for the viral precursors with different cleavage motifs. Only furin/PACE was fully capable of cleaving the precursors with the oligobasic motif. PC2 and PC1/PC3 were incapable or only partially capable of cleaving at this motif. None of the proteinases cleaved the monobasic motif. These results suggest involvement of furin/PACE in viral protein processing in the constitutive secretory pathway. PMID- 1404597 TI - Subgenomic RNAs mediate expression of cistrons located internally on the genomic RNA of tobacco necrosis virus strain A. AB - Upon infection of tobacco protoplasts, the genomic RNA of tobacco necrosis virus strain A (TNV-A) accumulates linearly in time. The accumulation patterns of the two subgenomic RNAs resemble those of endogenous mRNAs in that the peak levels are reached after several hours. The accumulation of the 1.3-kb subgenomic RNA is delayed by 1 h compared with that of the 1.6-kb subgenomic RNA, which illustrates the important role of the subgenomic RNAs in the regulation of TNV-A gene expression. The locations of the 5' nucleotides of the subgenomic RNAs reveal that the 5'-proximal cistrons of the 1.6- and 1.3-kb RNAs encode an 8-kDa protein from open reading frame (ORF) 3 and the coat protein from ORF 5, respectively. In a wheat germ translation system, a synthetic transcript resembling the 1.6-kb RNA expresses both ORFs 3 and 4. Moreover, the synthesis of the 6-kDa protein from ORF 4 depends on the translation efficiency of ORF 3, suggesting that in vivo, ORFs 3 and 4 are both expressed from the 1.6-kb RNA. The major in vitro translation product of TNV-A genomic RNA is the coat protein. We show that the region upstream of the coat protein promotes internal initiation of translation in vitro. However, this region is functionally inactive in vivo, suggesting that TNV-A genomic RNA is not important for coat protein synthesis in plants. PMID- 1404598 TI - Induction of E1A-responsive negative factors for transcription of the fibronectin gene in adenovirus E1-transformed rat cells. AB - The level of fibronectin (FN) gene expression is very high in resting rat 3Y1 cells but greatly decreased in adenovirus E1-transformed cells. To study the mechanism of this down-regulation, nuclear factors binding to the 5'-flanking region of the FN gene were analyzed by gel retardation assay and DNase I footprinting. Nuclear factors that were present in the transformed cells but nearly absent in resting 3Y1 cells interacted with multiple sites of the promoter region. Oligonucleotide competition with the FN promoter-chloramphenicol acetyltransferase (CAT) reporter constructs (pFCAT) for these factors in the transformed cells indicated that all of them had a negative effect on FN gene expression. Of them, a factor(s) (G10BP) binding to the G10 stretch from positions -239 to -230 and to two GC boxes consisting of the G10 stretch with one internal C residue insertion from positions -105 to -95 and -54 to -44 had the strongest repressive activity. Introduction of substitutive mutations into these G-rich sequences resulted in the increase in CAT activity of pFCAT in the transformed cells. The recognition sequences of G10BP and Sp1 overlap in two GC boxes. G10BP has stronger affinity for heparin and GC boxes than does Sp1, suggesting that G10BP may repress FN gene transcription by displacing Sp1. PMID- 1404599 TI - Transcription of viral late genes is dependent on expression of the viral intermediate gene G8R in cells infected with an inducible conditional-lethal mutant vaccinia virus. AB - There are three temporal classes of vaccinia virus genes: early, intermediate, and late. The object of this study was to determine the effects on virus replication of regulating the expression of G8R, an intermediate gene that encodes a late transcription factor. We inserted the lac operator adjacent to the RNA start site of the G8R gene in a recombinant vaccinia virus that constitutively expresses the Escherichia coli lac repressor to make expression of the G8R gene dependent on the inducer isopropyl-beta-D-thiogalactopyranoside (IPTG). In case repression would not be complete, we also weakened the promoter of the G8R gene by making a single-nucleotide substitution designed to reduce its basal level of transcription. The mutant virus replicated well in the presence of the inducer, although synthesis of the G8R-encoded 30,000-M(r) protein was only 10% of that of the wild-type virus. In the absence of IPTG, (i) synthesis of the G8R protein was inhibited by more than 99% relative to that of the wild-type virus, (ii) synthesis of early and intermediate mRNAs appeared to be unaffected, (iii) intermediate proteins accumulated to higher than normal levels, (iv) synthesis of late mRNA and protein was reduced by about 90%, (v) viral DNA was replicated but incompletely resolved concatemeric molecules accumulated, (vi) not even the earliest stages of virion assembly were detectable by transmission electron microscopy, and (vii) virus yield under one-step growth conditions and plaque formation were 10(-3) and 10(-4) times the wild-type values, respectively. The defect in late gene expression could be overcome by transfection of a G8R gene that was not under lac operator control, as well as by addition of IPTG, further demonstrating the specificity of the repression. The correlation between decreased expression of the G8R intermediate gene and inhibition of late mRNA synthesis is consistent with the notion that the G8R product serves as an essential late transcription factor and supports a cascade mechanism of vaccinia virus gene regulation. In addition, the inducer-dependent vaccinia virus mutant provided a tool for selective inhibition of late gene expression while allowing synthesis of early and intermediate mRNAs and proteins. PMID- 1404600 TI - Epstein-Barr virus latent membrane protein transactivates the human immunodeficiency virus type 1 long terminal repeat through induction of NF-kappa B activity. AB - The Epstein-Barr virus latent membrane protein (LMP) is an integral membrane protein that is expressed in cells latently infected with the virus. LMP is believed to play an important role in Epstein-Barr virus transformation and has been shown to induce expression of several cellular proteins. We performed a series of experiments that demonstrated that LMP is an efficient transactivator of expression from the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR). Mutation or deletion of the NF-kappa B elements in the LTR abolished the transactivation, indicating that the LMP effect on HIV expression was due to induction of NF-kappa B activity. Experiments in which the HIV-1 Tat protein was coexpressed in cells together with LMP showed that Tat was able to potentiate the transactivation. Surprisingly, a synergistic effect of the two proteins was observed even in the absence of the recognized target region for Tat (TAR) in the HIV-1 LTR. PMID- 1404601 TI - Mutations within the 5' nontranslated region of hepatitis A virus RNA which enhance replication in BS-C-1 cells. AB - Passage of human hepatitis A virus (HAV) in cell culture results in attenuation of the virus as well as progressive increases in the efficiency of virus replication in cell culture. Because the presence of identical mutations within the 5' nontranslated regions (5'NTRs) of several independently isolated cell culture-adapted HAV variants suggests that the 5'NTR may play a role in determining this change in virus host range, we constructed chimeric infectious cDNA clones in which portions of the 5'NTR of cell culture-adapted HM175/p35 virus were replaced with cDNA from either wild-type virus (HM175/wt) or a second independently isolated, but closely related cell culture-adapted virus (HM175/p16). Substitution of the complete 5'NTR of HM175/p35 with the 5'NTR of HM175/wt resulted in virus with very small replication foci in continuous African green monkey kidney (BS-C-1) cells, indicating that 5'NTR mutations in HM175/p35 virus are required for optimal growth in these cells. A chimera with the 5'NTR sequence of HM175/p16 retained the large foci of HM175/p35 virus, while the growth properties of other viruses having chimeric 5'NTR sequences indicated that mutations at bases 152 and/or 203 to 207 enhance replication in BS-C-1 cells. These findings were confirmed in one-step growth experiments, which also indicated that radioimmunofocus size is a valid measure of virus replication competence in cell culture. An additional mutation at base 687 of HM175/p16 had only a minor role in enhancing growth. In contrast to their effect in BS-C-1 cells, these 5'NTR mutations did not enhance replication in continuous fetal rhesus monkey kidney (FRhK-4) cells. Thus, mutations at bases 152 and/or 203 to 207 enhance the replication of HAV in a highly host cell-specific fashion. PMID- 1404602 TI - Macrophage-tropic human immunodeficiency virus isolates from different patients exhibit unusual V3 envelope sequence homogeneity in comparison with T-cell-tropic isolates: definition of critical amino acids involved in cell tropism. AB - Previous experiments indicate that the V3 hypervariable region of the human immunodeficiency virus (HIV) envelope protein influences cell tropism of infection; however, so far no consistent V3 sequence can account for macrophage or T-cell tropism. In these experiments, we studied infectious recombinant HIV clones constructed by using V3 region sequences of HIV isolates from 16 patients to search for sequences associated with cell tropism. Remarkable homology was seen among V3 sequences from macrophage-tropic clones from different patients, and a consensus V3 region sequence for patient-derived macrophage-tropic viruses was identified. In contrast, V3 sequences of T-cell-tropic clones from different patients were highly heterogeneous, and the results suggested that sequence diversity leading to T-cell tropism might be generated independently in each patient. Site-specific mutations identified amino acids at several positions on each side of the GPGR motif at the tip of the V3 loop as important determinants of tropism for T cells and macrophages. However, a wide variety of mutant V3 sequences induced macrophage tropism, as detected in vitro. Therefore, the homogeneity of macrophage-tropic patient isolates appeared to be the result of selection based on a biological advantage in vivo. PMID- 1404603 TI - Characterization of a baculovirus gene encoding a small conotoxinlike polypeptide. AB - We identified a gene of Autographa californica nuclear polyhedrosis virus (AcMNPV) that encodes a small cysteine-rich polypeptide which has size and sequence similarity to omega-conotoxins, a class of calcium ion (Ca2+) channel inhibitors, found in the venom of cone snails. Transcriptional analysis indicated that the 159-bp open reading frame, which we named ctl, and a downstream 984-bp open reading frame are transcribed as a single 1.3-kb bicistronic late RNA. The mature ctl gene product was identified as a small secreted protein by high pressure liquid chromatography fractionation of extracellular fluid. Viruses with a site-specific deletion in ctl appeared normal with regard to the kinetics and virulence of infection, both in vitro and in vivo. Although we studied the behavior of wild-type and mutant virus-infected insects in some detail, a biological role for ctl in AcMNPV infection remains to be established. PMID- 1404604 TI - Sequence similarity between Borna disease virus p40 and a duplicated domain within the paramyxovirus and rhabdovirus polymerase proteins. AB - We report the sequence of a Borna disease virus clone (pBDV-40) that encodes a 40 kDa protein (p40) found in the nuclei of infected cells. Comparative sequence analysis indicates that p40 is distantly similar to two different regions in the L-polymerase proteins encoded by paramyxoviruses and rhabdoviruses. The p40 sequence similarity indicates a previously undetected duplication in these viral polymerases. Phylogenetic reconstruction suggests that the gene that encodes p40 last shared a common ancestor with these viral polymerase genes prior to the duplication event. These findings support the hypothesis that Borna disease virus is a negative-strand RNA virus and suggest that p40 is involved in transcription and/or replication. The discovery of a duplication within the polymerase proteins of paramyxoviruses and rhabdoviruses has profound implications for the mapping of enzymatic activities within these multifunctional proteins. PMID- 1404606 TI - Mutational analysis of the gag-pol junction of Moloney murine leukemia virus: requirements for expression of the gag-pol fusion protein. AB - The gag-pol polyprotein of the murine and feline leukemia viruses is expressed by translational readthrough of a UAG terminator codon at the 3' end of the gag gene. To explore the cis-acting sequence requirements for the readthrough event in vivo, we generated a library of mutants of the Moloney murine leukemia virus with point mutations near the terminator codon and tested the mutant viral DNAs for the ability to direct synthesis of the gag-pol fusion protein and formation of infectious virus. The analysis showed that sequences 3' to the terminator are necessary and sufficient for the process. The results do not support a role for one proposed stem-loop structure that includes the terminator but are consistent with the involvement of another stem-loop 3' to the terminator. One mutant, containing two compensatory changes in this stem structure, was temperature sensitive for replication and for formation of the gag-pol protein. The results suggest that RNA sequence and structure are critical determinants of translational readthrough in vivo. PMID- 1404607 TI - Fusion mutants of Newcastle disease virus selected with monoclonal antibodies to the hemagglutinin-neuraminidase. AB - The Australia-Victoria (AV) isolate of Newcastle disease virus (NDV) induces fusion from within but not fusion from without. L1, a neuraminidase (NA) deficient virus derived from AV, has the opposite fusion phenotype from the wild type virus. It fails to induce the former mode of fusion, but has gained a limited ability to promote the latter. Monoclonal antibodies to antigenic site 23 on the hemagglutinin-neuraminidase (HN) glycoprotein have previously been shown to select variants of the AV isolate that have altered NA activity or receptor binding affinity. By using an antibody to this site, variants of L1 have been selected. Three of the variants have gained an increased affinity for sialic acid containing receptors, as evidenced by the resistance of their hemagglutinating activity to the presence of reduced amounts of sialic acid on the surface of chicken erythrocytes. All four variants still have very low levels of NA activity, comparable to that of the parent virus, L1. The alteration in receptor binding affinity results in a decreased potential for elution from cellular receptors and correlates with an increased ability to promote both modes of fusion. A single amino acid substitution in the HN protein of each variant, responsible for its escape from neutralization, has been identified. These studies identify two HN residues, 193 and 203, at which monoclonal antibody selected substitution influences the receptor recognition properties of NDV and may influence its ability to promote syncytium formation. PMID- 1404608 TI - Oligomerization of hepatitis delta antigen is required for both the trans activating and trans-dominant inhibitory activities of the delta antigen. AB - Two forms of hepatitis delta antigen (HDAg) have different roles in the replication cycle of hepatitis delta virus (HDV); the small forms trans activates HDV RNA replication, whereas the large form suppresses it but is needed for virion assembly. To understand the mechanism of these regulatory activities, we studied the possible HDAg oligomerization and its role in HDV replication. In this report, we provide direct biochemical evidence for the in vitro and in vivo formation of homodimers and heterodimers between these two HDAg species. By deletion mutagenesis, we showed that this protein interaction is mediated by the leucine zipper-like sequence residing in the N-terminal one-third of HDAg. Furthermore, site-specific mutants with various substitutions on two of the leucine residues in this stretch of sequence had reduced or no ability to form HDAg dimers. Correspondingly, the small HDAg with mutations in the leucine zipper like sequence had reduced abilities to trans activate HDV RNA replication. Similar mutations on the leucine zipper-like sequence of the large HDAg also resulted in loss of the ability of large HDAg to inhibit HDV RNA replication. The in vivo biological activities of both forms of HDAg (trans activation and trans dominant inhibition of HDV RNA replication, respectively) correlated with the extent of HDAg oligomerization in vitro. Thus, we conclude that the small HDAg participates in HDV RNA replication as an oligomer form and that the large HDAg inhibits HDV RNA replication as a result of its complex formation with small HDAg. A "black sheep" model for the mechanism of trans-dominant inhibition by the large HDAg is presented. PMID- 1404605 TI - Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation. AB - Previous studies of the genetic and biologic characteristics of human immunodeficiency virus type 1 (HIV-1) have by necessity used tissue culture derived virus. We recently reported the molecular cloning of four full-length HIV 1 genomes directly from uncultured human brain tissue (Y. Li, J. C. Kappes, J. A. Conway, R. W. Price, G. M. Shaw, and B. H. Hahn, J. Virol. 65:3973-3985, 1991). In this report, we describe the biologic properties of these four clones and the complete nucleotide sequences and genome organization of two of them. Clones HIV 1YU-2 and HIV-1YU-10 were 9,174 and 9,176 nucleotides in length, differed by 0.26% in nucleotide sequence, and except for a frameshift mutation in the pol gene in HIV-1YU-10, contained open reading frames corresponding to 5'-gag-pol-vif vpr-tat-rev-vpu-env-nef-3' flanked by long terminal repeats. HIV-1YU-2 was fully replication competent, while HIV-1YU-10 and two other clones, HIV-1YU-21 and HIV 1YU-32, were defective. All three defective clones, however, when transfected into Cos-1 cells in any pairwise combination, yielded virions that were replication competent and transmissible by cell-free passage. The cellular host range of HIV-1YU-2 was strictly limited to primary T lymphocytes and monocyte macrophages, a property conferred by its external envelope glycoprotein. Phylogenetic analyses of HIV-1YU-2 gene sequences revealed this virus to be a member of the North American/European HIV-1 subgroup, with specific similarity to other monocyte-tropic viruses in its V3 envelope amino acid sequence. These results indicate that HIV-1 infection of brain is characterized by the persistence of mixtures of fully competent, minimally defective, and more substantially altered viral forms and that complementation among them is readily attainable. In addition, the limited degree of genotypic heterogeneity observed among HIV-1YU and other brain-derived viruses and their preferential tropism for monocyte-macrophages suggest that viral replication within the central nervous system may differ from that within the peripheral lymphoid compartment in significant and clinically important ways. The availability of genetically and biologically well characterized HIV-1 clones from uncultured human tissue should facilitate future studies of virus-cell interactions relevant to viral pathogenesis and drug and vaccine development. PMID- 1404609 TI - Transcriptional analysis of multigene family 110 of African swine fever virus. AB - A transcriptional analysis of the 3.2-kb region of the African swine fever virus genome containing the five members of the multigene family 110 is presented. The mRNAs corresponding to the genes studied have short leader sequences with no intervening AUG codons before the translational start site, and their 3' ends map within a conserved sequence motif formed by a stretch of seven or more consecutive thymidylate residues. The possible role of this sequence as a signal for the 3'-end formation of African swine fever virus mRNAs is discussed. While four of the genes studied are actively transcribed from the beginning of the infection until the onset of virus DNA replication, the transcription of one of the members of the multigene family 110, the L270 gene, is silenced at an earlier time. A detailed analysis, including in vitro translation of mRNAs isolated from infected Vero cells, revealed that the L270 gene belongs to a small subset of early genes, designated immediate early, whose transcription is silenced before the onset of virus DNA replication. The transcriptional data obtained enabled us to generate the first detailed transcriptional map of a region of the African swine fever virus genome, thus opening the possibility of studying the cis-acting sequences involved in transcriptional control of the viral genes. PMID- 1404610 TI - Phenotypic progression of a rat lymphoid cell line immortalized by human T lymphotropic virus type I to induce lymphoma/leukemia-like disease in rats. AB - Rat lymphoid cells, TARS-1, immortalized by coculture with adult T-cell leukemia cells, were intraperitoneally injected into 65 newborn, inbred WKAH/Hkm rats. In most of the rats, tumor nodules were discernible 7 to 15 days after transplantation but were completely rejected within 5 to 6 weeks. Two rats with no tumor nodules exhibited gait disturbances and paralysis of the hind legs 3 to 4 weeks after transplantation. Histological and hematological examinations revealed that a lymphoma/leukemia-like disease had developed in one of the two rats, and the T-lymphoid cell line WLeuk-1 was established from peripheral blood mononuclear cells from this rat. When the WLeuk-1 cells were transplanted into newborn WKAH/Hkm rats, the animals died of a lymphoma/leukemia-like disease within several weeks after transplantation, in contrast to their rejection of the TARS-1 cells. Southern blot and karyotype analyses revealed that WLeuk-1 cells had retained the marker chromosomes and human T-lymphotropic virus type I (HTLV I) integration patterns of the parent cell line, TARS-1. The additional specific chromosome abnormalities 3p+,t (12;13), and Xq+ were found in the WLeuk-1 cells. Moreover, the expression of HTLV-I structural proteins was slightly depressed in WLeuk-1 cells, while that of the transacting factors p40tax and p21x, but not that of p27rex, was enhanced about fivefold compared with that in TARS-1. The transactivating function of p40tax was intact in WLeuk-1, as evidenced by enhanced interleukin-2 receptor alpha chain expression. These results suggest that aberrant expression of HTLV-I regulatory genes and alteration of cellular genes were associated with the phenotypic progression of the WLeuk-1 cell line. PMID- 1404611 TI - A recombinant human Fab expressed in Escherichia coli neutralizes rabies virus. AB - A recombinant human anti-rabies monoclonal antibody (MAb-57) Fab was prepared by cloning the heavy (Fd)- and light-chain domains into the same bacterial expression vector. To construct the recombinant Fab, mRNA was extracted from MAb 57-producing hybridoma cells, reverse transcribed, and then amplified by polymerase chain reaction (PCR) by using oligonucleotides specific for immunoglobulin heavy- and light-chain DNA sequences. PCR-amplified Fd-chain cDNA was fused, in frame, between a bacterial leader peptide (PelB) at the amino terminus and a 10-amino-acid peptide tag at the carboxy terminus. The PCR amplified lambda-chain cDNA was also fused to the PelB leader peptide. The immunoglobulin Fab was then expressed as a dicistronic message in bacteria by using the isopropyl-beta-D-thiogalactopyranoside-inducible lactose promotor (lacZ). DNA sequencing was used to define the gamma-chain isotype (immunoglobulin G1) and VH (VHI) chain and VL (V lambda II) chain gene usage. The recombinant Fab (rFab57) specifically bound the rabies virus coat glycoprotein, while the Fd and lambda chains, when expressed individually, did not. The binding specificity of rFab57 was indistinguishable from that of the intact MAb in direct enzyme-linked immunosorbent assays; however, the dissociation constant of rFab57 for rabies virus protein G was approximately 1 log10 U lower than that of complete MAb-57 in competition enzyme-linked immunosorbent assays. A fluorescent-focus inhibition assay showed that bacterially expressed rFab was capable of neutralizing rabies virus strain CVS-11. We conclude that a human Fab expressed in bacteria maintains its specificity and biologic activity. PMID- 1404613 TI - Maturation cleavage required for infectivity of a nodavirus. AB - Nodaviral morphogenesis involves formation of labile precursor particles, called provirions, which mature by autocatalytic cleavage of the 407-residue coat precursor protein between asparagine residue 363 and alanine residue 364. It has previously been demonstrated that maturation results in increased physicochemical stability of the virion. We show here that cleavage of coat protein in purified provirions of Flock House virus was accompanied by a five- to eightfold increase in specific infectivity. Cleavage-negative provirions, produced by site-directed mutagenesis of asparagine residue 363 to aspartate, threonine, or alanine, displayed no infectivity above revertant frequencies as measured by plaque assay. All viable revertants (nine of nine) restored asparagine to the mutated position, suggesting high specificity for asparagine at the cleavage site. PMID- 1404612 TI - Coexpression of the simian immunodeficiency virus Env and Rev proteins by a recombinant human adenovirus host range mutant. AB - Recombinant human adenoviruses (Ads) that replicate in the intestinal tract offer a novel, yet practical, means of immunoprophylaxis against a wide variety of viral and bacterial pathogens. For some infectious agents such as human immunodeficiency virus (HIV), the potential for residual infectious material in vaccine preparations must be eliminated. Therefore, recombinant human Ads that express noninfectious HIV or other microbial proteins are attractive vaccine candidates. To test such an approach for HIV, we chose an experimental model of AIDS based on simian immunodeficiency virus (SIV) infection of macaques. Our data demonstrate that the SIV Env gene products are expressed in cultured cells after infection with a recombinant Ad containing both SIV env and rev genes. An E3 deletion vector derived from a mutant of human Ad serotype 5 that efficiently replicates in both human and monkey cells was used to bypass the usual host range restriction of Ad infection. In addition, we show that the SIV rev gene is properly spliced from a single SIV subgenomic DNA fragment and that the Rev protein is expressed in recombinant Ad-SIV-infected human as well as monkey cells. The expression of SIV gene products in suitable live Ad vectors provides an excellent system for studying the regulation of SIV gene expression in cultured cells and evaluating the immunogenicity and protective efficacy of SIV proteins in macaques. PMID- 1404614 TI - Activation of the prolactin receptor gene by promoter insertion in a Moloney murine leukemia virus-induced rat thymoma. AB - The prolactin receptor (Prlr) and growth hormone receptor (Ghr) genes and the Moloney murine leukemia virus integration-2 (Mlvi-2) locus were mapped to mouse chromosome 15 and human chromosome 5 bands p12-p14. To examine the potential relationship between Mlvi-2 and the genes encoding the growth hormone receptor and the prolactin receptor, we determined the chromosomal location of all three loci in the rat, using a panel of rat-mouse somatic cell hybrids, and in the mouse, using a panel of (C57BL/6J x Mus spretus)F1 x C57BL/6J interspecific backcross mice. These analyses revealed that Ghr, Prlr, and Mlvi-2 map to chromosome 2 in the rat and to chromosome 15 in the mouse, in close proximity with each other. Pulsed-field gel electrophoresis of rat genomic DNA showed no overlaps between the gene encoding the prolactin receptor and the remaining loci. Moreover, expression of the prolactin receptor was not affected by provirus insertion in Mlvi-2. During these studies, however, we detected one T-cell lymphoma line (2779) in which the prolactin receptor gene was activated by provirus integration. Sequence analysis of polymerase chain reaction-derived cDNA clones showed that the prolactin receptor RNA message initiates at the 5' long terminal repeat and utilizes the splice donor site 5' of the gag gene to splice the viral sequences onto exon 1 of the prolactin receptor. This message is predicted to encode the intact prolactin receptor protein product. Exposure of the T-cell lymphoma line 2779 to prolactin promoted cellular proliferation. PMID- 1404615 TI - An adenosine at position 27 in the human immunodeficiency virus type 1 trans activation response element is not critical for transcriptional or translational activation by Tat. AB - Tat protein binds to the trans-activation response (TAR) element of human immunodeficiency virus type 1 RNAs and activates gene expression at the level of transcription in mammalian cell lines and translation in Xenopus oocytes. Certain residues within TAR are important for Tat binding in vitro, including residue A 27, which appears to be able to be modified in a Tat-dependent manner in Xenopus oocytes (L. Sharmeen, B. Bass, N. Sonenberg, H. Weintraub, and M. Groudine, Proc. Natl. Acad. Sci. USA 88:8096-8100, 1991). Activation by Tat in oocytes occurs via a covalent modification of TAR-containing RNA. We have found that in both mammalian cells and Xenopus oocytes, conversion of A-27.U-38 or C-27.G-38 or C 27.G-38 reduces activation. However, conversion to G-27.U-38 or G-27.C-38 had little or no effect on activation, and in oocytes, these mutant RNAs were still covalently modified. These data exclude a specific role for the adenosine at residue 27 for Tat activation but suggest a requirement for a purine at this position. PMID- 1404616 TI - Protein truncation is not required for c-myb proto-oncogene activity in neuroretina cells. AB - The v-myb oncogene of avian myeloblastosis virus (AMV) differs from its normal cellular counterpart by a truncation at both its amino and carboxyl termini and by a substitution of 11 amino acid residues. We had previously shown that v-myb containing AMV, in the presence of basic fibroblast growth factor, transformed chicken neuroretina (CNR) cells. To understand the mechanism of c-myb activation, we have tested whether avian retroviruses that express the full-length c-Myb are also active on CNR cells. We have found that c-Myb, like v-Myb, strongly increases the basic fibroblast growth factor response of CNR cells and that these c-myb-expressing cells are able to grow in soft agar in the presence of the growth factor. We have also found that, in contrast to normal or v-myb-expressing AMV-transformed CNR cells, c-Myb-transformed cells express mim-1, a granulocyte specific gene. However, normal v-Myb- and c-Myb-expressing CNR cells all express the pax-QNR gene, a newly described paired and homeobox-containing gene specifically expressed in the neuroretina. We conclude that, in contrast to what has been described for hematopoietic cells, overexpression of c-Myb is sufficient to activate gene expression and to induce an abnormal behavior of CNR cells. PMID- 1404618 TI - Human immunodeficiency virus type 1 gag-protease fusion proteins are enzymatically active. AB - We have introduced mutations into the region of the genome of human immunodeficiency virus type 1 (HIV-1) that encodes the cleavage sites between the viral protease (PR) and the adjacent upstream region of the polyprotein precursor. Segments containing these mutations were introduced into plasmids, and the retroviral proteins were expressed in Escherichia coli. The mutations prevented cleavage between the PR and the adjacent polypeptide; however, other PR cleavage sites in the polyprotein were cleaved normally, showing that the release of free PR is not a prerequisite for the appropriate processing of HIV-1 precursors. PMID- 1404617 TI - Minimal requirements for the human immunodeficiency virus type 1 V3 domain to support the syncytium-inducing phenotype: analysis by single amino acid substitution. AB - The third variable domain (V3) of the human immunodeficiency virus type 1 external envelope contains determinants of cell tropism, cytopathicity, and infectivity and elicits antibodies able to block infectivity in vitro and in vivo. Our study encompassed point-mutational analysis of HXB-2 viruses containing patient-derived V3 regions and expressing a non-syncytium-inducing, low replicating phenotype in T-cell line SupT1. The mutation within V3 of a serine at position 306 into an also naturally occurring arginine (S to R) required an additional, naturally occurring mutation at position 320 (aspartate to glutamine, D to Q) or 324 (aspartate to asparagine, D to N) for full expression of the syncytium-inducing, high-replicating (SI) phenotype. The naturally occurring mutation of an aspartate into an arginine at position 320 (D to R) was sufficient for production of the SI phenotype. This study proves that introduction of a positively charged amino acid at position 306 or 320, previously shown to be strongly associated with the SI phenotype in field isolates (R.A.M. Fouchier, M. Groenink, N.A. Kootstra, M. Tersmette, H.G. Huisman, F. Miedema, and H. Schuitemaker, J. Virol. 66:3183-3187, 1992), is minimally required for production of SI viruses. In addition, naturally occurring mutations at residue 324 also modulate the virus phenotype. PMID- 1404619 TI - Restoration of cell surface CD4 expression in human immunodeficiency virus type 1 infected cells by treatment with a Tat antagonist. AB - Productive infection of T lymphocytes with human immunodeficiency virus type 1 (HIV-1) is accompanied by a diminution of surface CD4 receptors. Treatment of chronically HIV-1-infected CD4-negative T cells in vitro with the Tat antagonist Ro 5-3335 resulted in a drug dose-dependent decrease in virus protein production and a reciprocal increase in surface CD4 display. The drug-treated cells remained viable, showed significantly reduced levels of the full-length and spliced HIV-1 mRNAs as detected by Northern (RNA) blot hybridization, and maintained integrated HIV-1 DNA. In immunoprecipitation studies with drug-treated cells, the levels of free 55-kDa CD4 protein increased and gp160 complexed with CD4 decreased in amount. These results show for the first time that certain cytopathogenic effects of chronic HIV-1 infection can be reversed by suppressing virus expression. PMID- 1404620 TI - Transcription of human respiratory syncytial virus genome RNA in vitro: requirement of cellular factor(s). AB - Extracts made from human respiratory syncytial virus (RSV)-infected Hep-2 cells synthesized mRNAs encoded by all known viral genes. In contrast, RSV ribonucleoproteins purified from infected cells failed to transcribe in vitro; transcription was restored by addition of a cytoplasmic extract of uninfected Hep 2 cells, demonstrating that a cellular factor(s) has a role in RSV gene expression. Quantitation of the individual gene mRNAs transcribed in vitro revealed polarity of transcription of the genome. PMID- 1404621 TI - Genetic recombination in brome mosaic virus: effect of sequence and replication of RNA on accumulation of recombinants. AB - In order to facilitate the isolation of recombinants in brome mosaic virus, a series of duplication mutants with alterations in the RNA3 3' noncoding region has been engineered. The distribution of crossovers, which was observed to be dependent on the parental RNA3 sequence, supported the role of RNA structure in recombination. However, a negative correlation between replication of the parental RNA3 constructs and the accumulation of recombinant progeny confirmed the role of selection. PMID- 1404622 TI - Baculovirus gp64 envelope glycoprotein is sufficient to mediate pH-dependent membrane fusion. AB - The baculovirus gp64 envelope glycoprotein is a major component of the envelope of the budded virus (BV) and is involved in BV entry into the host cell by endocytosis. To determine whether gp64 alone was sufficient to mediate membrane fusion, the Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus gp64 protein was transiently expressed in uninfected insect cells. Cells expressing the baculovirus gp64 protein were examined for membrane fusion activity by using a syncytium formation assay under various conditions of exposure to low pH. Cells expressing the gp64 protein mediated membrane fusion and syncytium formation in a pH-dependent manner. A pH of 5.5 or lower was required to induce membrane fusion. In addition, exposure of gp64-expressing cells to low pH for as little as 5 s was sufficient to induce gp64-mediated syncytium formation. These studies provide direct evidence that gp64 is a pH-dependent membrane fusion protein and suggest that gp64 is the protein responsible for fusion of the virion envelope with the endosome membrane during BV entry into the host cell by endocytosis. PMID- 1404623 TI - Laparoscopic operative retroperitoneoscopy: use of a new device. AB - Attempts at retroperitoneoscopy have mostly failed in the past due to the inability to create an effective pneumoretroperitoneum because of the dense areolar tissue binding the fat in the retroperitoneum, which could not be broken down merely by pneumo-insufflation. The newly devised balloon breaks the septae, lifts the peritoneum atraumatically and creates a workable space in the retroperitoneum. The view of the retroperitoneal structures provided is satisfactory. With this balloon dissector we have performed laparoscopic ureterolithotomy, renoscopy and renal biopsy, para-aortic lymph node biopsy and ligation of the internal spermatic vein. PMID- 1404624 TI - Laparoscopic cystectomy: initial report on a new treatment for the retained bladder. AB - The retained bladder of a 27-year-old paraplegic woman suffering from recurrent pyocystis was removed laparoscopically. Operative time was 130 minutes. Postoperative hospital stay was 5 days, which was significantly less than that in 5 similar patients undergoing open cystectomy for vesical empyema in whom the mean hospital stay was 20.6 days. We believe that laparoscopic cystectomy represents a plausible, minimally invasive alternative to standard cystectomy for the symptomatic bladder left behind after supravesical urinary diversion. PMID- 1404625 TI - Stimulated release of urine histamine in interstitial cystitis. AB - The diagnosis of interstitial cystitis is primarily made based on clinical and cystoscopic findings with exclusion of other bladder diseases. Despite all of the efforts at definitive identification, interstitial cystitis lacks universal objective findings. Mast cell activation with associated histamine release has been postulated as an etiological factor leading to the symptom complex associated with interstitial cystitis. To investigate this hypothesis, a 3-step controlled prospective study was conducted. In step 1 reliability of urine histamine assay was critically examined, and the assay was established to be simple, reliable and valid. In step 2 random spot urine histamine levels (basal state) were measured in 25 noninterstitial cystitis and 15 interstitial cystitis patients (22.1 +/- 0.95 ng./ml. versus 19.2 +/- 1.19 ng./ml.). There was no significant difference in the random urine histamine levels between the 2 groups (p greater than 0.05). In step 3 urine histamine levels were measured before and after hydrodistention (acute stimulation) in 7 noninterstitial cystitis controls and 6 newly diagnosed interstitial cystitis patients under general anesthesia. The urine histamine-to-creatinine ratio was used to correct for the dilutional effect of normal saline used during hydrodistention. The urine histamine-to creatinine ratios of the control group showed no significant difference before and after hydrodistention. However, the difference in the urine histamine-to creatinine ratios of the interstitial cystitis group compared to the controls before and after hydrodistention was highly significant (p less than 0.001). Although measurement of random spot urine histamine alone (basal state) was not found useful to make the diagnosis of interstitial cystitis, measurement of urine histamine before and immediately after hydrodistention (acute stimulation) may become an important objective parameter to assist in the diagnosis of interstitial cystitis. PMID- 1404626 TI - Monoclonal antibody Ki-67 in the study of the proliferative activity of bladder carcinoma. AB - We studied the proliferative activity of bladder carcinoma using monoclonal antibody Ki-67, which is able to stain a nuclear antigen exclusively present in cells in the cell cycle, that is with activated deoxyribonucleic acid (DNA). We used this immunohistochemical technique on neoplastic tissue removed by transurethral resection from 101 patients. A significant correlation was observed (p less than 0.003) between cells with activated DNA and histological grading, even though within the context of each grade we observed tumors with a different proliferation index. Furthermore, we studied the location of the activated cells in the context of the tumor. In invasive tumors (stages T1 to T4) cells with activated DNA were always present at the base of implant of the tumor and in the neoplastic tissue that infiltrates the bladder wall. In regard to noninvasive tumors (stage Ta), in 57% of the cases most cells with activated DNA were present in the vegetative portion of the tumor and there were no recurrences at followup, while in 43% of the cases such cells were present also or especially at the base of implant of the tumor, near the lamina propria. In the latter patients we observed a 94% recurrence rate. These results suggest that the immunohistochemical assessment of the proliferative activity of transitional tumors of the bladder, using monoclonal antibody Ki-67, and the evaluation of the location of stained neoplastic cells provide a more reliable estimate of biological aggressiveness than that obtained with histopathological patterns alone. PMID- 1404627 TI - Whole bladder wall photodynamic therapy with in situ light dosimetry for carcinoma in situ of the bladder. AB - We report on the preliminary results of 12 patients with multifocal carcinoma in situ of the bladder treated with whole bladder wall photodynamic therapy. The total light dose (scattered plus nonscattered light) measured in situ was 100 joules per cm.2 in the first 6 patients (group 1) and 75 joules per cm.2 in the remaining 6 (group 2). These light doses correspond on the average to 27 joules per cm.2 and 15.5 joules per cm.2 nonscattered light as reported by other investigators. Followup ranged from 6 to 22 months (average 11.5). In group 1, 2 tumors recurred after 6 and 9 months, respectively, and 2 other patients had a permanently shrunken bladder without evidence of disease. In group 2, 1 tumor recurred 5 months after photodynamic therapy. In this group the bladder capacity increased on the average to 135% of the pretreatment value 3 months after photodynamic therapy. All recurrences were in patients with a history of invasive bladder cancer (stages T1 and T2). These preliminary results demonstrate the importance of in situ scattered light dosimetry for minimizing local side effects of whole bladder photodynamic therapy. PMID- 1404628 TI - Urethral controlled bladder substitution: a comparison between the intussuscepted nipple valve and the technique of Le Duc as antireflux procedures. AB - A urethral controlled bladder substitute was constructed from a detubularized, double folded ileal segment in 40 male patients following cystoprostatectomy for bladder cancer. For reflux prevention patients were prospectively randomized to receive either an intussuscepted nipple valve or the ureters were implanted by the Le Duc mucosal trough technique. All patients had normal upper tracts preoperatively. Mean patient age, performance status and stage of cancer were comparable in both groups. Patients were evaluated 6 to 18 months postoperatively. In addition to history taking, assessment included excretory urography, ascending cystography and voiding cystourethrography. During the observation period all patients with nipple valves had normal radiographic appearance of the upper tracts without evidence of reflux. On the other hand, following the Le Duc procedure 12 of 38 renal units (31%) showed evidence of radiographic dilatation. Of the 12 units 11 had stenotic ureters and 1 had reflux. We conclude that nipple valves are more effective in reflux prevention and protection of the upper urinary tract in patients for whom an ileal neobladder is indicated. PMID- 1404629 TI - Magnetic resonance imaging of traumatic posterior urethral defects and pelvic crush injuries. AB - A total of 18 patients 4 to 71 years old with complete occlusion of the prostatomembranous urethra from pelvic crush injury underwent magnetic resonance imaging (MRI) of the pelvis just before open urethroplasty. MRI studies included T2-weighted sagittal and coronal images as well as transaxial T1 and T2-weighted spin-echo images. Operative findings and erectile function were correlated with MRI findings. All patients underwent conventional cystography and retrograde urethrography. The mean interval from injury to operation was 5.5 months (range 3 to 12 months) and followup averaged 12 months (range 3 to 40 months). Posttraumatic pelvic anatomy can be distorted and imaging in all 3 planes was needed. The severity and direction of prostatourethral dislocation, and the length of the urethral defect could be accurately determined, which often is not possible with conventional radiographic studies. MRI also demonstrated injuries at many locations along the erectile pathway, including sacral and ischial fractures as well as fractures and avulsions of the cavernous bodies. Pelvic MRI can accurately define the pelvic anatomy after crush injury and, therefore, it can provide useful preoperative information that cannot be obtained by conventional radiographic studies. Our results correlating MRI findings of cavernous avulsion with clinical impotence require further study. PMID- 1404630 TI - Successful outcome of artificial urinary sphincters in men with post prostatectomy urinary incontinence despite adverse implantation features. AB - A total of 75 men with post-prostatectomy urinary incontinence underwent artificial urinary sphincter implantation with a mean followup of 3.7 years. Average patient age at implantation was 67 years, with 30 men being 70 years old or older. In only 15 men (20%) was there no adverse implantation feature, while the remainder had adverse features, such as detrusor hyperactivity (44), bladder neck or urethral stricture disease (27), previous radiation therapy (11) and metastatic prostate cancer (11). Although men with ideal implantation characteristics, men with normal detrusors and men who underwent prostatectomy for benign disease had slightly better outcome in terms of urinary continence, in general each group of men with and without adverse features had satisfactory urinary continence. Other than men with a benign prostate, who fared better, each group of men with and without adverse features had equal need for device revisions. In conclusion, men with post-prostatectomy urinary incontinence should not be excluded from consideration for artificial urinary sphincter implantation based on the failure to meet ideal implantation criteria provided such adverse features are recognized and appropriately addressed. PMID- 1404631 TI - The hemodynamic pathophysiology of impotence following blunt trauma to the erect penis. AB - A total of 19 patients provided a history of impotence following blunt trauma to the erect penis during intercourse or masturbation, or after accidents. Corporeal veno-occlusive dysfunction was the most common hemodynamic abnormality (16 of 19 patients, or 84%). A site-specific leak, which consisted of abrupt filling of the dorsal vein and/or corpus spongiosum from a focal site on the penile shaft, was demonstrated in 15 patients (79%). Cavernous artery insufficiency was found less often (7 of 19 patients, or 37%). A focal mid shaft cavernous artery occlusion was demonstrated in 5 patients (28%). It is hypothesized that the aforementioned hemodynamic abnormalities are caused by tunica and intracavernous vasculature injuries induced by the marked short-term pressure increases, which approach or exceed the tunica tensile strength during acute abrupt loading of the erect penis. This hypothesis is supported by direct recording of intracavernous pressures that exceeded 450 mm. Hg in response to angulation and manual compression of the penile shaft. Further evidence was created by a biomechanical model that was based on previously published intracavernous pressure- circumference patient data during dynamic infusion pharmacocavernosometry. Using a typical patient data set a 60% diminution of circumference at the site of abrupt loading was calculated to induce a 15% increase in circumference in the nonloaded portion of the penile shaft and an elevated intracavernous pressure exceeding 900 mm. Hg. The site-specific hemodynamic abnormalities were found to occur not only in patients with a classical penile fracture history but also in patients with injuries during masturbation or following accidents who had no acute penile swelling or ecchymosis. Thus, the erect penis is at risk for injury during any acute loading situation. It is likely that this erect trauma-induced hemodynamic pathology occurs more frequently than previously appreciated and that this type of impotence may be the underlying basis for many cases of idiopathic Peyronie's disease. PMID- 1404632 TI - Objective double-blind evaluation of erectile function with intracorporeal papaverine in combination with phentolamine and/or prostaglandin E1. AB - We performed a double-blind, crossover study using objective measurements to compare maximum rigidity and duration of erections with papaverine hydrochloride in combination with phentolamine mesylate and/or prostaglandin E1. The rationale for the protocol was to combine a smooth muscle relaxant (papaverine) with either or both vasodilating agents (phentolamine and prostaglandin E1) commonly used for injection therapy. The 7 volunteer patients with organic impotence documented by abnormal nocturnal penile tumescence testing were injected with 0.5 to 1.0 ml. papaverine (30 mg./ml.) in combination with phentolamine (0.5 mg./ml.) and/or prostaglandin E1 (5 micrograms./ml.). Each patient received 2 injections on each of 2 testing dates; injection 2 was given after tumescence resulting from injection 1 had subsided completely. The medications were given in a randomized, counterbalanced order following double-blind procedures. Patients evaluated the erections subjectively. In addition, the RigiScan device was used to measure maximum rigidity and duration of erections. All patients observed increased duration of erections with both combinations containing prostaglandin E1. Analysis of RigiScan measurements showed no statistically significant differences for maximum rigidity (p greater than 0.1) but significantly greater duration of erections with papaverine plus prostaglandin E1, and papaverine plus phentolamine plus prostaglandin E1 compared to papaverine plus phentolamine (p less than 0.001). There was no statistical difference in rigidity or duration of erections between papaverine plus prostaglandin E1 and papaverine plus phentolamine plus prostaglandin E1. No patient reported significant penile pain with any of the injections. We conclude that the combination of papaverine and prostaglandin E1 produces erections of longer duration than papaverine plus phentolamine and that no additional benefit is gained by adding phentolamine to a combination of papaverine and prostaglandin E1. Further studies are in progress to define optimal dose response curves for papaverine and prostaglandin E1 as individual agents and in combination. PMID- 1404633 TI - Results of surgical management of Peyronie's disease. AB - Peyronie's disease is often managed surgically when medical management fails and sexual function is impaired due to residual curvature or loss of erectile function. In this study 63 patients were treated surgically, with 25 receiving a penile prosthesis, 25 undergoing a tunica vaginalis graft and 13 undergoing the Nesbit ellipse procedure. The long-term surgical outcome as determined by sexual function indicated that the penile prosthesis group remained the most sexually active, followed by the Nesbit ellipse group with the tunica vaginalis graft group being the least sexually active. Incision of curvature with placement of a penile prosthesis for the surgical management of Peyronie's disease remains an approach that has excellent long-term functional results. PMID- 1404634 TI - Sclerotherapy with tetracycline for hydroceles in renal transplant patients. AB - A total of 17 patients with hydroceles following renal transplantation underwent sclerotherapy with tetracycline hydrochloride (10 ml. of a 5% solution of tetracycline in 1% lidocaine). A successful outcome was obtained in 15 patients (88%). Post-sclerotherapy hydrocelectomy was necessary in 2 patients (12%). No major complications (testicular loss, scrotal abscess or necrosis) occurred in any patient. Pain at injection was the only adverse effect. Tetracycline sclerotherapy for hydroceles appears to be an effective and safe procedure in the renal transplant population. We recommend this procedure as the initial treatment modality for hydroceles in patients with a renal allograft. PMID- 1404635 TI - Intraoperative varicocele anatomy: a macroscopic and microscopic study. AB - Varicoceles are found in approximately 15% of all men in the general population and up to 41% of all infertile men. However, the exact location and relationship of internal and external spermatic arteries, veins and lymphatics within the inguinal portion of the spermatic cord have not been previously well described in infertile men. The results of detailed intraoperative macroscopic and microscopic surgical dissections of the spermatic cord and gubernaculum of 83 infertile men with 115 palpable varicoceles are described. Enlarged veins exiting the testis and traversing the gubernaculum were present in 48% of the dissections. Enlarged external spermatic veins were detected in 74% of all spermatic cords. Typically, small internal spermatic veins drained into a large vein more proximally in the spermatic cord. An average of 3.6 lymphatics per spermatic cord was identified and preserved during the dissections. A solitary testicular artery was observed in 69% of the dissections. The testicular artery was adherent to the posterior surface of a large internal spermatic vein in 50% of the dissections and was surrounded by a dense complex of closely adherent veins in 30%. To decrease the incidence of postoperative varicocele recurrences we suggest a surgical approach that addresses all identifiable dilated and connecting veins. These findings suggest that surgical approaches that include intraoperative access to and ligation of low inguinal (external spermatic) and gubernacular veins may cause fewer recurrences, unligated small internal spermatic veins may be a cause of varicocele recurrence, and large internal spermatic veins should be individually identified, dissected and ligated since the testicular artery and lymphatics are often adherent to these veins. Optical magnification is important to facilitate identification of lymphatics, testicular arteries and small internal spermatic veins. PMID- 1404636 TI - Management of preexisting inflatable penile prosthesis during radical retropubic prostatectomy. AB - A potentially difficult technical situation exists when a man with a functioning inflatable penile prosthesis elects radical prostatectomy as treatment for localized prostate cancer. Between February 1988 and June 1991 we encountered 8 men with a preexisting inflatable penile prosthesis who subsequently underwent radical retropubic prostatectomy. In 2 patients the reservoir portion of the prosthesis was in the perivesical space such that radical prostatectomy could be performed without difficulty. However, in 6 patients removal of the reservoir was necessary to complete the prostatectomy. In 3 of these 6 patients the reservoir was replaced at 3 to 6 months after radical prostatectomy and all 3 systems function well. The remaining 3 patients have not yet elected replacement of the reservoir. Only 1 patient had an infection and a complication attributable to the prosthesis. We believe that a preexisting inflatable penile prosthesis should not preclude successful radical retropubic prostatectomy, although temporary removal of the reservoir may be required. PMID- 1404637 TI - Retrieval of proximally migrated ureteral stents. AB - Proximal migration of Double-J ureteral stents is a rare complication. An atraumatic and effective method of retrieving the dislodged stent using a ureteral balloon is described. PMID- 1404638 TI - Selective sacral rhizotomy in the management of the reflex neuropathic bladder: a report on 17 patients with long-term followup. AB - During the last 6 years 24 patients with cervical or thoracic spinal cord injuries and a severe reflex neuropathic bladder underwent selective dorsal sacral rhizotomy with the aid of intraoperative neurostimulation and urodynamic monitoring. Preoperative and postoperative evaluation was available in 17 patients. Followup ranged from 2 months to 5 years (mean 32 months). Mean bladder capacity increased significantly after rhizotomy (from 148 +/- 28.1 to 377 +/- 52.9 ml., p less than 0.001), as did mean volume to first contraction (from 99 +/ 28.6 to 270 +/- 39.3 ml., p less than 0.001). No significant changes in bowel or erectile function were noted. Continence was improved in 94%, with 14 patients remaining completely dry and voiding with electrical stimulation or intermittent self-catheterization. The long-term results of selective sacral rhizotomy compare favorably to more aggressive alternatives, such as augmentation cystoplasty or urinary diversion. PMID- 1404639 TI - Effect of spinal cord ischemia on vesicourethral function. AB - We studied 9 patients with clinical evidence of spinal cord ischemia or infarction who had altered vesicourethral function. Of the patients 6 had some preservation of bladder and lower extremity sensation, a clinical pattern consistent with the anterior spinal artery syndrome. A total of 3 patients had a clinical picture more consistent with complete transverse myelopathy, since they had no preservation of bladder or lower extremity sensation. Despite sensory levels well above the sacral spinal cord segments, 6 patients had detrusor areflexia (4 with bethanechol supersensitivity and 4 with neuropathic changes in the perineal electromyograph) indicating longitudinal spinal cord involvement. Three patients had detrusor hyperreflexia with vesicosphincter dyssynergia, indicating some preservation of the sacral spinal cord. In 6 patients appreciation of pinprick in the lower extremities was absent or decreased but light touch or position sense was preserved. Bladder sensation was dissociated in 4 of these 6 patients, since they had perception of bladder distention but loss of urge to void. These findings indicate that bladder distention is a sensory modality probably mediated via the posterior spinal cord, while the sense of urgency is probably conveyed by the anterior spinal cord. PMID- 1404640 TI - Unilateral renal cystic disease: a case presentation. AB - An infant who presented with a unilateral renal cystic process underwent nephrectomy due to hypertension. There was no evidence of any other disease process. Family history and investigation were negative for renal cystic disease or other genetic disease process. The pathology most resembled autosomal dominant polycystic kidney disease or a specific entity described as unilateral renal cystic disease. PMID- 1404641 TI - Managing apparent ureteropelvic junction obstruction in the newborn. AB - A total of 97 newborns with apparent ureteropelvic junction obstruction was evaluated from mid 1984 to 1989. Evaluation and management are described. Of these patients 39 with an affected kidney showing good initial differential function (greater than 35%) by diethylenetriaminepentaacetic acid scan and 2 showing diminished function (less than 35%) were followed nonoperatively. Six patients (15%) eventually required pyeloplasty for diminishing function (4), urinary tract infections (1) or symptoms of colic (1). The 4 patients with diminishing function improved after pyeloplasty to at least the initial level. A total of 12 patients with good initial function (greater than 35%) of the affected kidney underwent early pyeloplasty (within 6 weeks of diagnosis). They were compared to the similar group of patients managed nonoperatively and followed by sequential renal scans. Eventual changes in percentage differential function in the nonoperative and early surgery groups were +2.8% and +4.1%, respectively. Changes in extraction factor were +0.8% (nonoperative group) and +0.9% (surgery group). No statistically significant difference was found. In the kidney with apparent ureteropelvic junction obstruction and good function, an initial nonoperative approach with sequential renal scan followup and pyeloplasty as needed appears to be reasonable and has resulted in no permanent loss of function. PMID- 1404642 TI - Postpubertal genitourinary function following posterior urethral disruptions in children. AB - A total of 24 boys sustaining a simultaneous pelvic fracture and posterior urethral disruption was observed from the time of injury through puberty. Average length of followup was 6 years. In contrast to the adult, in whom the urethra is invariably injured at the prostatomembranous junction, the posterior urethral disruptions in the prepubertal patient were at 3 distinct locations: 1) supraprostatic in 4 patients, 2) transprostatic in 4 and 3) prostatomembranous in 16. Prolonged followup through puberty in these children revealed that the frequency of complications was significantly higher for urethral injuries proximal to the prostatomembranous region compared to those at this latter site: impotence 75% versus 31%, intractable strictures following repairs 75% versus 12% and urinary incontinence 25% versus 0%. In summary, the prognosis of children who sustain a posterior urethral disruption should be based on the location of the injury and must remain guarded until the individual attains a postpubertal status. PMID- 1404643 TI - Transpubic-perineal urethral reconstruction in boys using a substitution graft. AB - A combined transpubic-perineal 1-stage approach was used for urethral replacement and proximal urethral repair in 6 boys: 4 were treated for a long proximal urethral stricture secondary to trauma and 2 with urethral atresia underwent replacement of the entire anterior urethra. All patients underwent a urethral substitution graft of either skin or bladder mucosa. Followup ranged from 2 to 8 years with all patients continent. PMID- 1404644 TI - Congenital rupture of scrotum: an unusual complication of meconium peritonitis. AB - Congenital rupture of the scrotum caused by meconium peritonitis occurred in a newborn with clinical findings of the Beckwith-Wiedemann syndrome. Ruptured omphalocele and jejunal atresia were present. Surgical repair 3 hours after birth was successful. PMID- 1404645 TI - Transitional cell carcinoma associated with crossed renal ectopia and previous cyclophosphamide therapy. PMID- 1404646 TI - Spontaneous regression of histologically proved pulmonary metastases from renal cell carcinoma: a case with 5-year followup. AB - Spontaneous regression of biopsy proved metastatic renal cell carcinoma is rare. We describe a 39-year-old man who had histologically proved metastatic disease to the lungs after nephrectomy. The lesions had spontaneously regressed 3 months later. The patient remained without evidence of recurrence 5 years after diagnosis. PMID- 1404648 TI - Paratesticular fibrous pseudotumor in a patient with Gorlin's syndrome: nevoid basal cell carcinoma syndrome. AB - An 18-year-old man with Gorlin's syndrome (the nevoid basal cell carcinoma syndrome) underwent excisional biopsy of a fibrous pseudotumor of the tunica vaginalis. Preoperative ultrasound confirmed the extraparenchymal nature of this paratesticular lesion, permitting a transscrotal approach. The pathophysiological considerations suggest that this finding (to our knowledge the first such case reported in association with Gorlin's syndrome) may be more than coincidental. PMID- 1404647 TI - Complete ureteral transection associated with percutaneous lumbar disk nucleotomy. AB - A case of complete ureteral transection complicating percutaneous nucleotomy for disk herniation is reported. The ureteral lesion was contralateral to the percutaneous approach and was treated by intubated ureteroureterostomy, since complete section precluded endourological management. PMID- 1404649 TI - Malignant Leydig cell tumor of the testis in complete remission on o,p' dichlorodiphenyl-dichloroethane. AB - A 56-year-old patient is described who presented with retroperitoneal lymph node metastases 2 years after resection of a Leydig cell tumor of the left testis. The patient did not suffer from endocrinological imbalance. Surgical removal of the metastases alleviated abdominal symptoms for 1 year. o,p'-Dichlorodiphenyl dichloroethane (o,p'-DDD) treatment was started at the time of recurrence of the retroperitoneal mass and the appearance of a hepatic metastasis. Tumors were remarkably responsive to o,p'-DDD, since 2 complete remissions could be obtained for extended periods. The o,p'-DDD was tolerated reasonably well and serum levels of 15 to 20 mg./l. were sustained for many months. Unfortunately, the patient could not be cured with this effective treatment. PMID- 1404650 TI - Osteitis pubis as a complication of transrectal needle biopsy of the prostate. AB - We report a case of osteitis pubis complicating transrectal needle biopsy of the prostate. This case best supports direct trauma to the symphysis pubis as an etiology. A literature review of osteitis pubis is presented. PMID- 1404651 TI - Adenocarcinoma in a mullerian duct cyst. AB - A case of adenocarcinoma involving a mullerian duct cyst is presented. The presentation, treatment, and pathological and radiological appearance are discussed. The embryology and history of this entity are reviewed. PMID- 1404652 TI - Re: Pelvic pain without pelvic organs. PMID- 1404653 TI - Re: Venogenic impotence following dermal graft repair for Peyronie's disease. PMID- 1404654 TI - Suppression of prostaglandin E1-induced pain by dilution of the drug with lidocaine before intracavernous injection. PMID- 1404655 TI - Full-term pregnancy obtained with sperm recovered by seminal tract washout from an anejaculating, spinal cord injury man. PMID- 1404656 TI - Re: Staging relationships and outcome in early stage testicular cancer: a report from the Testicular Cancer Intergroup Study. PMID- 1404657 TI - Re: Antegrade approach to radical retropubic prostatectomy in patients with difficult apical dissection. PMID- 1404658 TI - Progression delay of prostate tumor skeletal metastasis effects by bisphosphonates. AB - Prostate tumor cell metastasis to the axial skeleton was induced in male Copenhagen rats using the intravenous injection of syngeneic metastatic R3327 MATLyLu tumor cells and concomitant caval vein clamping. The proliferation of tumor cells in the lumbar region was monitored by the progression, within 19 days post tumor cell injection, of hindleg paralysis which appeared in these animals. Histology confirmed the presence of tumor cells within the lumbar spine in 100% of cases displaying hindleg paralysis. Treatment with either of the bisphosphonate drugs, Cl2MDP or APD, suppressed and delayed the development of hind leg paralysis. Bisphosphonate treatment may be expected to delay the onset of axial skeletal metastasis effects in prostate cancer patients. PMID- 1404659 TI - Ureteral compliance and histology in partial obstruction in a canine model. AB - Standardized partial ureter obstruction was achieved in 35 mongrel dogs in whom ureteral compliance and its relationship to histologic changes were studied over a period of 26 weeks. The partially obstructed ureter became dilated with thickened wall and showed muscle hypertrophy and connective tissue proliferation. The normal stellate configuration of the ureteral lumen gradually flattened and became entirely circular by the eighth week. The compliance of the obstructed ureter increased gradually after one, 2, 4, and 8 weeks but decreased thereafter at 12 and 26 weeks. At 8 weeks, the ureter was significantly more compliant than both, the unobstructed control ureter (p less than 0.005) and the 12 week and 26 week partially obstructed ureters (p less than 0.005 & p less than 0.05 respectively). The increase in ureteral compliance was proportional to the amount of muscle hypertrophy during the first 8 weeks while the subsequent decrease in compliance (at 12 and 26 weeks) was proportional to the amount of connective tissue proliferation. This study documents ureteral response, both functional and histologic, to partial obstruction in a canine model over 26 week duration. PMID- 1404660 TI - Localization and identification of T-(Gal beta 1-3GalNAc alpha 1-O-R) and T-like antigens in experimental rat bladder cancer. AB - A mouse monoclonal antibody and a rabbit polyclonal antibody against the T antigen (Gal beta 1-3GalNAc alpha 1-O-R) were used to study the distribution of T antigens in an experimental rat bladder cancer model. Neoplasia was induced in 28 rats by intravesical installation of N-nitroso-N-methylurea (NMU) dissolved in acetate buffer. Fifteen rats were installed with acetate buffer, and served as controls. Urothelial samples were taken from all animals, the atypia was graded and detailed data on the location of the antibody binding structures were obtained by immunohistochemical methods. In addition, Western Blots of glycoproteins and thin-layer-chromatography (TLC) immunostainings of glycolipids extracted from normal and malignant tissue were performed to characterize the molecules presenting T-antigens. Examination of the histologic distribution of T antigens showed that both the monoclonal and the polyclonal reagents reacted with atypical cells in proportion to the grade of atypia, but showed no reaction in invasive cells. These results confirm previously obtained data on the T-antigen using peanut (arachis hypogaea) agglutinin (PNA), and support the structure identity as being the classical O-linked mucin type T-antigen. Western blots of tumor glycoproteins showed that the monoclonal and the polyclonal antibody reacted with epitopes different from that of PNA, but all the probes correlated with atypia. In addition PNA, as the only anti-T reagent, bound to glycolipid. By using well characterized and highly specific immunological reagents the present study shows that the T-antigen is a highly selective marker of urothelial atypia. PMID- 1404661 TI - Mechanism of ammonium transport: inhibition by potassium and barium. AB - Elucidating the precise mechanism of intestinal ammonium transport is critical to the understanding of the acidosis associated with intestinal urinary diversion. Unfortunately, it is incompletely understood and controversial. Recently, we have shown that furosemide and Ba2+ significantly inhibit ammonium absorption in the ileum. On the basis of this and other data, we have suggested that ionized ammonium absorption occurs via K(+)-transport pathways. The present study examines intestinal ammonium absorption and its inhibition by K+ and Ba2+ utilizing a simplified in vivo system in rat distal ileum. Ammonium absorption demonstrates a tendency towards saturation at initial concentrations between 0 and 300 mM/l. Above 300 mM/l. there was a marked increase in ammonium absorption suggesting a possible biological effect of high NH4+ concentrations on the intestinal segment. Potassium inhibits ammonium absorption. K+ (50 mM/l.) significantly inhibited ammonium at an initial concentration of 100 mM/l. (p less than 0.05) and K+ (100 mM/l.) inhibited ammonium absorption at both 50 and 100 mM/l. (p less than 0.05 and p less than 0.01 respectively). Potassium inhibition of ammonium absorption was lost at concentrations above 200 mM/l. suggesting that K+ inhibition occurs via a competitive mechanism. Ba2+ (25 mM/l.) was shown to be a potent inhibitor of ammonium absorption. This significant inhibition persisted at high initial ammonium concentrations suggesting a complex, noncompetitive mechanism of inhibition. In conclusion, this study provides important data further suggesting that ammonium transport in the intestine occurs via K+ transport pathways, and suggests that the traditionally held mechanism of nonionic ammonium diffusion needs reevaluation. PMID- 1404662 TI - Alterations in bile following urinary intestinal diversion. AB - In order to determine whether alterations in bile occur which make it more lithogenic when intestinal segments are interposed in the urinary tract, 42 female Sprague-Dawley rats had intestinal and urointestinal manipulations followed by analysis of bile constituents. Timed collections were obtained from the common bile duct which were analyzed for bile acids, phospholipids, cholesterol, bilirubin, volume, osmolality, pH, calcium, chloride, sodium, and potassium. Changes in bile constituents were identified following urinary diversion which were specific for the type of diversion and the segment of bowel used, but they were not of sufficient degree to cause significant changes in the lithogenicity of bile. This correlates well with the lack of clinical findings of cholelithiasis in children with urinary intestinal diversion. PMID- 1404663 TI - Endothelin in the urinary bladder. I. Synthesis of endothelin-1 by epithelia, muscle and fibroblasts suggests autocrine and paracrine cellular regulation. AB - The synthesis and localization of endothelin-1 were studied in human and rabbit bladder. In addition, the effects of endothelin-1 on smooth muscle tone and cholinergic neurotransmission were investigated in rabbit bladder. Endothelin like immunoreactivity was localized in the transitional epithelium, serosal mesothelium, and vascular endothelium; smooth muscle of the bladder (non vascular) and that of blood vessels; and fibroblasts. With in situ hybridization, transcripts of endothelin messenger ribonucleic acid (mRNA) were localized with the same cellular distribution as endothelin-like immunoreactivity, in bladder tissue. Northern blot analysis of bladder RNA confirmed the expression of preproendothelin-1 mRNA. Rabbit bladder strips in organ chambers contracted when exposed to endothelin-1 and this response was partially attenuated by calcium channel blockers or by removal of extracellular calcium. Transmural electrical stimulation of rabbit bladder strips elicited contractions that were greatly reduced by atropine. The remaining atropine resistant component was blocked by alpha, beta-methylene ATP, which desensitizes purinergic receptors. Endothelin-1 caused a small but consistent attenuation of the atropine sensitive component of the neurogenic contraction, while it had no effect on the atropine resistant component. The localization of endothelin synthesis in epithelia, smooth muscle, and fibroblasts suggests that endothelin may act as an autocrine hormone in the regulation of the bladder wall structure and smooth muscle tone. In addition, endothelin-1 may regulate cholinergic neurotransmission by a paracrine mechanism. PMID- 1404665 TI - A mechanism of retrograde ejaculation after bilateral hypogastric nerve transections in the dog. AB - To pursue the mechanism of retrograde ejaculation after bilateral hypogastric nerve transections, the disability of the lumbosacral sympathetic trunk and the spermatic nerve to compensate bladder neck closure was investigated while both act as compensatory pathways for seminal emission. Five mongrel dogs were used for each experiment. By manual penis-stimulation, all dogs showed only retrograde ejaculation one month and six months after transection of bilateral hypogastric nerves. Bladder neck closure did not occur by electrical stimulation of either the lumbosacral sympathetic trunk or the spermatic nerve before and one month after transection of bilateral hypogastric nerves in all dogs examined and persistent relaxation of bladder neck was observed one and six months after transection of bilateral hypogastric nerves. The present results and our previous data indicate that retrograde ejaculation after bilateral hypogastric nerve transections is attributable to the absence of effective compensatory sympathetic pathways for bladder neck closure under the recovery of seminal emission by compensatory pathways. PMID- 1404664 TI - Endothelin in the urinary bladder. II. Characterization of endothelin receptor subtypes. AB - Endothelins (ET-1, ET-2, ET-3) are a family of regulatory peptides with diverse biological functions, including modulation of smooth muscle tone. To evaluate the possible role of endothelins in the control of the detrusor smooth muscle of urinary bladder, we have investigated the responses of isolated strips of bladder dome and base to endothelins, in organ chambers, and characterized the receptors for these isopeptides in bladder membranes. ET-1, ET-2 and to a lesser extent ET 3 caused sustained concentration-dependent contraction of bladder dome and base. The contraction to endothelins, unlike the short-lived contraction produced by cholinergic agents, was long lasting and difficult to wash out. Equilibrium binding studies demonstrated that endothelin isoforms bound to bladder membrane receptors specifically, with high affinity (KD of 0.4-0.6 nM) and limited capacity (60-420 fmol/mg protein). Competition analysis showed two populations of receptors: one with high affinity for ET-1 and ET-2 and low affinity for ET-3 and another with high affinity for ET-1, ET-2 and ET-3. Chemical affinity labeling of endothelins to bladder membranes demonstrated that ET-1 and ET-2 were cross linked to three proteins (75, 52 and 34 kDa, respectively), whereas ET-3 was cross-linked mainly to a 34 kDa protein. The data obtained from equilibrium binding studies, competition analysis and cross-linking experiments suggest that at least two endothelin receptor subtypes exist in bladder tissue. These observations further suggest that bladder smooth muscle tone may be modulated by endothelin or an endothelin-like substance via interaction with specific receptor sites. PMID- 1404666 TI - The expression of C-jun and junB mRNA in renal cell cancer and in vitro regulation by transforming growth factor beta 1 and tumor necrosis factor alpha 1. AB - The proto-oncogene C-jun acts as a transcriptional activator or repressor for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. JunB inhibits c-jun's transforming activities. We investigated the expression of jun genes in renal cell cancer (RCC) and their regulation by cytokines and transforming growth factor beta 1 (TGF-b1). The constitutive expression of c-jun was detected in 39 of 43 fresh frozen RCC, 5 of 10 normal kidneys, and the expression of junB detected in 28 of 34 RCC, 5 of 6 normal kidneys. C-jun was also found expressed in all 10 RCC tumor lines examined and junB was expressed at low levels in 6 of 10 renal tumor lines. TGF-b1 and tumor necrosis factor alpha (TNF-a) have been shown to alter the expression of jun genes in other tissue types. Additionally, TGF-b1, TNF-a, and gamma interferon (g-IFN) were shown to inhibit the growth of RCC. We found that TGF-b1 highly augmented the expression of junB (mean of 34 folds, p less than .05), but did not significantly alter the expression of c-jun, the transforming gene. In contrast, TNF-a significantly enhanced the expression of both c-jun (mean fold enhancement of 2.1, p less than .05) and junB (2.2 folds, p less than .05). Interleukin-2 (IL-2), interleukin-4 (IL-4) and g-IFN did not significantly alter jun expression. The findings presented suggest that c-jun may have a role in inducing malignant transformation in RCC and a novel mechanism by which TGF-b1 may exert its anti-tumor effects, via the activation of junB. Additionally, although TGF-b1, TNF-a, and g-IFN all have anti-proliferative actions on RCC in vitro, they were found to have different effects in altering jun expressions. PMID- 1404667 TI - Effects of adenosine on canine penile erection. AB - We investigated the hemodynamic effects of intracavernous injection of adenosine on canine penile erection. In all ten dogs studied, adenosine induced a dose dependent increase of intracavernous pressure (ICP). Adenosine (0.67 to 15 micrograms/kg., B.W.) increased arterial blood flow by 83 to 325 percent above baseline levels and also increased venous resistance, which resulted in a full erection (ICP = 80 to 140 cm. H2O) for one to 7 minutes. The repeatability of the adenosine effect was confirmed in eight dogs. We found that adenosine, by virtue of its smooth muscle relaxation properties, can induce a dose-dependent increase of ICP and cause a full erection in dogs. PMID- 1404668 TI - Prophylactic and therapeutic carboprost tromethamine bladder irrigation in rats with cyclophosphamide-induced hemorrhagic cystitis. AB - Recently, prostaglandins have been shown to be effective agents for the treatment of cyclophosphamide-induced hemorrhagic cystitis. Among the prostaglandins studied is carboprost tromethamine, a PGF2a analog. To determine the effectiveness of carboprost tromethamine therapy on the urothelium, we induced hemorrhagic cystitis in 81 rats. These were divided into two treatment arms. One arm was treated prophylactically at the time of cyclophosphamide injection, and the other started treatment only after hemorrhagic cystitis was established. Animals were divided equally into groups receiving 0, 0.4, 0.8, and 1.6 mg.% carboprost tromethamine in 0.9% normal saline by continuous bladder irrigation. All bladders were examined grossly for edema and hemorrhage, then histologically for mucosal ulceration, congestion, and perivascular hemorrhage. Results from the prophylactic arm, as compared to those for controls, revealed that all groups except those treated only with 0.9% normal saline had a lower incidence of hemorrhagic cystitis (p less than 0.05). In the established hemorrhagic cystitis arm, the group treated with 1.6 mg.% carboprost tromethamine showed the best response (p less than 0.05), whereas the group treated with 0.9% normal saline showed the poorest response. This study reveals that hemorrhagic cystitis in the rat model may be prevented by prophylactic continuous bladder irrigation with carboprost tromethamine, whereas established hemorrhagic cystitis may be treated effectively with intravesical instillation of carboprost tromethamine. Although the mechanism of action of this prostaglandin on the urothelium is unknown, it appears grossly and histologically to decrease ulceration, perivascular hemorrhage, and congestion in the mucosa and submucosa. PMID- 1404669 TI - Synergy of radiation therapy and immunotherapy in murine renal cell carcinoma. AB - The treatment of metastatic renal cell carcinoma with immunotherapy has resulted in objective anti-tumor responses in 15-30% of patients. To enhance the therapeutic effects of immunotherapy, it is becoming evident that this approach should be combined with other treatment modalities. In this study, a spontaneously metastasizing murine renal adenocarcinoma (Renca), transplanted under the renal capsule, was treated with either radiation therapy, immunotherapy or a combination of both. In order to distinguish between the local and systemic effects of radiation therapy, total body irradiation was compared to irradiation of the tumor-bearing kidney only, or irradiation of the whole mouse with the tumor-bearing kidney shielded. Immunotherapy was administered with interleukin-2 (IL-2) alone or with IL-2 and lymphokine activated killer (LAK) cells. Combined radiation and immunotherapy induced a better anti-tumor response than either modality alone. The best response was obtained by local tumor irradiation and IL 2 therapy and resulted in a significant reduction in primary tumor size, elimination of lung metastases and a significant increase in survival. PMID- 1404670 TI - A new porphyrin photosensitizer (PH1008) in model membranes, normal cells, and bladder cancer cells. AB - Newer photosensitizers continue to be sought for photodynamic therapy of bladder cancer particularly since local rather than systemic application is desired. Recent studies have indicated that a cationic dye, PH1008, a 13,17-N,N,N dimethylethylethanolamine ester of protoporphyrin, sensitizes the photolysis of red blood cells. The study described in this report was designed to investigate the plasma membrane partitioning of PH1008 model lipid system and to compare partitioning of PH1008 in normal transitional cells and bladder cancer cells in vitro. Partition coefficient (Kp) values characterizing the distribution of PH1008 between aqueous buffer and normal and malignant transitional cells were 3.4 +/- 0.7 x 10(4) (CRL-7881) and 9.5 +/- 1.4 x 10(4) (HTB-9), resulting in a 20% difference in membrane photosensitizer concentration at a particular photosensitizer concentration. Significantly higher (2-5 fold) differences are observed between tumor and surrounding normal tissue for systemically delivered photofrin II. Cell-bound drug was 30-fold (CRL-7881) and 80-fold (HTB-9) more fluorescent when compared to aqueous buffer. The combined effects of partitioning and bound fluorescence suggest that a 3.2-fold increase in fluorescence of transformed vs. normal bladder urothelium exists. This difference in fluorescence suggests that PH1008 might be more useful as a diagnostic tool than as a phototherapeutic agent. PMID- 1404671 TI - Effects of acute in vitro overdistension of the rabbit urinary bladder on DNA synthesis. AB - Urinary bladder outflow obstruction induces a myriad of structural and functional changes in the organ. Among the morphological responses to outlet obstruction is both hyperplasia and hypertrophy of specific cellular elements. The initial event which has been implicated in the initiation of the response to outflow obstruction is an initial period of high intravesical pressure and subsequent distention of the bladder. In a previous study, it was shown that at one day following partial outlet obstruction there was a marked increase in thymidine labelling of the urothelium, at 3-5 days, the labeling shifted from the urothelium to the interstitial and serosal elements. The current study was designed to determine if acute distention of the urinary bladder can induce an increase in DNA synthesis (3H-thymidine incorporation), and localize the increased DNA synthesis via autoradiography of 3H-thymidine. In this study, the bladders of adult male New Zealand white rabbits were mounted in isolated in vitro baths. Each control bladder was filled to either 5 or 20 ml. with saline, or distended to 120% of capacity. The bladders were incubated for 7 hours at which time 3H-thymidine was placed both within and outside the bladder for an additional one hour. At the end of the time the bladder was divided at the ureteral orifices into bladder body and base, and each body and base divided into two sections. One section of bladder body and base was quantitatively analyzed for both labelled and unlabelled DNA; the second section was fixed and prepared for autoradiography. The results can be summarized as follows: 1) Acute overdistention for 8 hours induced a slight decrease in the DNA concentration which was mediated by edema of the bladder wall. 2) Acute overdistention induced a 5-fold increase in 3H-thymidine incorporation in the bladder body and a 3-fold increase in the bladder base. Radioautoradiography of the overdistended bladders showed significant and substantial labelling which was confined to the urothelial basal cells. The control bladders showed little or no labelling. These results are consistent with the theory that acute distention following partial outlet obstruction initiates the proliferative response of the bladder to outlet obstruction, and the urothelium is the initial target of the proliferative response. Functionally, the proliferative response may serve to maintain the structural as well as functional integrity of the bladder. PMID- 1404672 TI - Three-dimensional intravascular ultrasound imaging of normal and diseased canine and human arteries. AB - This study reports three-dimensional reconstruction of two-dimensional intravascular ultrasound images obtained along 5 cm vessel segments. Each three dimensional image was produced by computerized "stacking" of a set of consecutive two-dimensional images (mode 90 images per set; range 32 to 256). Three dimensional images (n = 26) were obtained from 11 human normal and atherosclerotic arteries (three in vitro and eight in vivo) and five in vivo canine studies. In vivo human examinations included three iliac, one deep, and three superficial femoral arteries and one aortic dissection. Five in vivo canine vessels (three iliac stenoses and two aortic dissections) were imaged before and after intraluminal stent deployment. Images were displayed on a gray-scale monitor, allowing examination of vessel images as complete cylinders or longitudinal hemisections in any user-defined plane. This enabled global examination of vascular segments and identified luminal shape, wall thickness, and distribution and morphology of plaques. Reconstructions of aortic dissections illustrated the extent of the dissection and produced an anatomic picture of the false lumen. Three-dimensional imaging enhanced stent deployment by identifying the site for deployment, dimensions of the vessel lumen, and changes in morphology after stent insertion. There was good correlation in vessel dimensions measured by angiography, two-dimensional intravascular ultrasonography and longitudinal gray-scale reconstructions (r = 0.74 to 0.95; p = 0.34 to 0.001) but poor correlation with measurements from three-dimensional surface-rendered images (r = 0.13 to 0.48; p = 0.42 to 0.87). We conclude that three-dimensional intravascular ultrasound imaging is an innovative new method for identifying the type, extent, and spatial configuration of arterial disease, with promising diagnostic and therapeutic applications. PMID- 1404673 TI - Accuracy of duplex scanning for measurement of arterial volume flow. AB - This study examined the accuracy of duplex ultrasound measurements of volume flow in a baboon model. Volume flow (Vf) through the external iliac artery was calculated from measurements of blood velocity averaged over several cardiac cycles (time-averaged velocity [TAV]) and vessel cross-sectional area (A) measured from the B-mode image: Vf = TAV x A. Fourteen anesthetized baboons were studied with a duplex scanner with a 7 MHz imaging transducer and 5 MHz pulsed Doppler. B-mode ultrasound measurements of external iliac artery diameters (2.5 +/- 0.2 mm) were used for calculation of cross-sectional area. Timed blood collections obtained through a cannula inserted into the common femoral artery and TAV measurements were obtained simultaneously during 6 to 15-second intervals. These measurements were repeated three to five times per animal with different flow rates each time. Flow rates ranged from 56 to 280 ml/min (170 +/- 54 ml/min). Average velocity was 55 +/- 17 cm/sec. There was no significant difference between the two methods of volume flow measurement (Student t test). Linear regression analysis revealed a high degree of correlation (r = 0.90, slope 0.95, and p = 0.0001). The absolute percentage error was 13% +/- 8%. Volume flow measured by duplex scanning correlates highly with timed blood collections. This method has potential application for the evaluation of diseased arteries and bypass grafts whose rates of flow and waveform patterns are similar to those of this experiment. PMID- 1404674 TI - Color Doppler imaging of infrainguinal arterial occlusive disease. AB - Few reports in the literature validate the use of color Doppler imaging (CDI) for the evaluation of lower extremity arterial occlusive disease, particularly in the tibial and peroneal arteries. This prospective, blinded study compares CDI to arteriography to address the following questions: (1) how well does CDI visualize arterial segments, including those below the knee? and (2) can CDI alone accurately classify the degree of occlusive disease? Twenty-nine men undergoing arteriography before a lower extremity arterial reconstructive procedure were studied with a color ultrasound scanner from the level of the inguinal ligament to the ankle. Color images were examined for the presence or absence of triphasic flow, poststenotic turbulence, color bruits, and collateral vessels. Among 636 arterial segments adequately visualized by arteriography, > or = 90% were identified with color Doppler imaging, including the tibial and peroneal arteries. With color criteria only, specificity was > or = 92% for distinguishing < 50% from > = 50% lesions and > or = 93% for differentiating patent from occluded arteries. Sensitivity for detecting an occlusion was > or = 97% in the superficial femoral (SFA) and popliteal arteries and 83% in the tibial vessels. For identifying a > or = 50% stenosis, sensitivity was > or = 85% in the SFA and popliteal arteries but only 79% and 86% in the posterior and anterior tibial arteries, respectively. CDI reliably identifies vessel location from the level of the groin to the ankle. For the detection of occlusions, CDI is an accurate screening tool in the SFA and popliteal arteries but is less accurate in the tibial vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404675 TI - Developmental anomalies at the thoracic outlet: an analysis of 200 consecutive cases. AB - Anatomic observations were made during 200 consecutive transaxillary surgical procedures performed in 175 patients because of unremitting signs and symptoms of nerve or vascular compression at the thoracic outlet. There were 160 cases of brachial plexus compression and 40 cases of arterial or venous occlusion. In 132 (66%) of these cases, single or multiple abnormalities were recognized that represented developmental variations previously described in anatomic dissections or in embryologic studies. There were 17 cases of cervical rib or first thoracic rib abnormalities and 20 supernumerary scalene muscles. Developmental variations were identified in 86 scalene and 39 subclavius muscles or their insertions. Comparisons revealed a higher percentage of developmental anomalies in this group of patients than in consecutive anatomic investigations reported in unselected populations. This information was interpreted in light of recent embryologic studies and histochemical and morphometric ultrastructural studies of scalene muscle. The preponderance of evidence suggests that neurovascular compression in the region of the thoracic outlet derives from a combination of these factors: predisposing morphologic variations, structural modifications conditioned by functional requirements, and changes in fiber type or myosin isoform consequent to trauma. The correlation of clinical syndrome with morphologic characteristics alone was significant only for the Paget-Schroetter syndrome. PMID- 1404676 TI - Peripheral vascular disease in heart transplant recipients. AB - The improved longevity of heart transplant recipients demands heightened awareness of the long-term complications of the procedure. Between 1979 and 1990, 232 patients received 241 heart transplants at our institution. Accelerated coronary atherosclerosis occurred in 45 (19%) of the 232 patients, typically appearing within 2 years of transplantation, whereas peripheral vascular disease (PVD) appeared in 23 (10%) of the 232 patients, usually within 3 years of transplantation. In the patients with PVD, 13 had occlusive disease, nine had aneurysms, and one patient suffered a vertebral artery dissection. Accelerated coronary atherosclerosis afflicted 12 (52%) of the 23 patients affected by PVD (p < 0.05) and preceded the development of PVD in all 12. Logistic regression analysis revealed risk factors predictive of the development of PVD after transplantation to be a pretransplant history of ischemic cardiomyopathy and posttransplant hypertension and hypertriglyceridemia (p < 0.05), with the presence of more than one risk factor increasing the probability of development of PVD. Those patients thus identified as at risk should be closely monitored for the development of PVD. Aggressive medical management of hypertension and hyperlipidemia in this subpopulation may forestall or prevent the development of peripheral vascular disease after heart transplantation. PMID- 1404677 TI - Long-term results of compression treatment for lymphedema. AB - Although numerous operations have been devised for lymphedema, most surgeons manage this vexing condition by nonsurgical means. Previous studies by us showed that high-pressure (90 to 100 torr) sequential external pneumatic compression (SEP) reduced both limb girth and volume in a lymphedematous extremity. To assess the long-term effects of a program entailing (1) SEP, (2) elastic compression stockings to maintain the post-SEP girth, and (3) daily skin care, we reviewed the long-term courses of 49 patients managed by one surgeon. Limb girths measured at nine levels on the limb were obtained serially in follow-up (mean 25 months) by an independent observer to provide an objective response to therapy. The relative reduction in lymphedematous tissue was determined by the difference between the pretreatment, postacute treatment, and long-term treatment girths at nine points in the limb. In long-term follow-up, 26 of the patients maintained a full response (reduction at > 3 levels), whereas 10 maintained a partial response (reduction at < or = 3 levels). At late follow-up, calf and ankle girths were reduced by an absolute value of 5.37 +/- 1.01 and 4.63 +/- 0.88 cm in the full response group and 5.43 +/- 1.58 and 3.98 +/- 1.18 cm in the partial-response group over pretreatment measurements. The degree of subcutaneous fibrosis in relationship to the duration of the edema appeared to influence results greatly. The treatment of lymphedema with SEP and compression stockings is associated with long-term maintenance of reduced limb girth in 90% of patients. PMID- 1404678 TI - CHAT analysis of the influence of specific risk factors on late results after carotid endarterectomy. AB - The CHAT classification separates various current and historical presentations of cerebrovascular disease in an effort to determine important prognostic clues for management and prognosis. To evaluate known risk factors for late stroke and death, we followed up for an average of 44 months 633 patients who had undergone 714 carotid operations. We analyzed the indication for surgery (by CHAT) and the effect of preoperative risk factors (age, hypertension, cardiac disease, tobacco use, diabetes, hyperlipidemia, renal disease, pulmonary disease, and total risk factor score) on the end points of late stroke and death. Ipsilateral stroke was uncommon after carotid endarterectomy: with life-table analysis, the probability of late stroke at 5 years after carotid endarterectomy was 3%. Among the 127 patients with amaurosis fugax, the incidence of late stroke and of mortality was a combined total of 1% per year, and the 17 patients who had been first seen with permanent ocular stroke (blindness) fared equally well. The 28 patients who were first seen with vertebrobasilar symptoms and were treated by carotid endarterectomy also fared particularly well, with no late strokes or deaths within the first 5 years. Logistic regression analyses revealed that the various indications for carotid endarterectomy were associated with differing patterns of risk factors as significant predictors of late stroke or death. For patients first seen with asymptomatic lesions, only diabetes was an important predictor for late stroke (p = 0.05) and renal disease was the only marker for early death (p = 0.05). On the other hand, those factors were not significant risk factors for patients first seen with amaurosis fugax, for whom tobacco use was a negative predictor for stroke (p = 0.06) and male gender a negative predictor for early death (p = 0.03). After cortical transient ischemic attacks and carotid endarterectomy, there were no risk factors predictive of late stroke or of death. For patients with prior stroke, age was a very strong predictor of stroke (p = 0.01) and both age and a history of cardiac disease were significant risk factors for early death (p = 0.007). In contrast to the results in reports of patients treated medically for transient ischemic attacks and stroke, we found that several risk factors appeared to play relatively minor roles. In conclusion, stroke after carotid endarterectomy was uncommon, least common after ocular symptoms, and most likely after permanent cortical stroke. Specific risk factors were less important for patients after carotid endarterectomy than for the medically treated stroke patient. PMID- 1404679 TI - Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis. The VA Cooperative Asymptomatic Carotid Artery Stenosis Study Group. AB - We prospectively analyzed adverse effects of aspirin in a multicentered cooperative study undertaken to determine the role of endarterectomy in the treatment of asymptomatic carotid artery stenosis. Persons with active peptic ulcer disease or known intolerance to aspirin were excluded from the study. Patients initially received 650 mg aspirin twice daily. After a 54-month recruitment period, 444 patients in 11 centers were followed up for as many as 8 years (mean 47.9 +/- 27.9 months). Patients intolerant to 650 mg aspirin twice daily could be switched to enteric-coated aspirin or "low-dose" aspirin (80 to 325 mg daily). At the conclusion of the study, we performed a cross-sectional analysis of aspirin usage and complications. Overall, there were 757 episodes reported wherein adjustments in study medications were made, including cessation and change in formulation or dosage. At the conclusion of the study, at the time of death, or at occurrence of a neurologic end point, 16% of patients were off medication entirely, 51% had been converted to enteric-coated aspirin, and only 33% were taking regular aspirin with 27% of those having been placed on a reduced dosage. Adverse reactions were ascertained from 4954 patient visit records. In all there were a total of 837 adverse reactions reported, or one in every 5.9 visits. The most frequently reported reaction was heartburn or stomach pain for which 372 episodes were reported in 184 (42%) patients. Nausea or vomiting occurred on 79 occasions in 58 patients, and bloody stools were reported 52 times in 41 patients. We conclude that high-dose aspirin therapy for asymptomatic carotid artery stenosis is poorly tolerated and that adverse reactions even to low-dose enteric-coated aspirin are common even in patients screened for aspirin intolerance. PMID- 1404681 TI - Magnetic resonance angiography of the carotid artery combining two- and three dimensional acquisitions. AB - To assess the agreement between magnetic resonance angiography and conventional angiography in the evaluation of carotid stenosis, 61 carotid arteries of 40 patients were studied by combined two- and three-dimensional magnetic resonance angiography and conventional angiography. Stenosis of the internal carotid artery was categorized as mild, moderate, severe, critical, or complete occlusion. In 42 arteries, the degree of stenosis according to magnetic resonance angiography correlated exactly to that found by conventional angiography. In the remaining 19 carotid arteries, the magnetic resonance angiographic measurement of stenosis differed from the conventional angiographic measurement by only one size category. The Spearman rank correlation coefficient was 0.95 (p < 0.001). This study showed that by combining information from two- and three-dimensional magnetic resonance angiographic studies and making use of the advantages of each method, magnetic resonance angiography was comparable to conventional angiography in determining carotid stenosis. Magnetic resonance angiography tended to demonstrate a higher level of stenosis when there was a discrepancy. These data demonstrate that magnetic resonance angiography is a steadily improving technology. Although additional studies need to be done, it seems clear that magnetic resonance angiography will be an imaging modality comparable in accuracy to conventional angiography. PMID- 1404680 TI - Polytetrafluoroethylene interposition grafts for carotid reconstruction. AB - Polytetrafluoroethylene interposition grafts were used for carotid reconstruction in 26 operations performed in 23 patients during a 7-year period. There were 10 men and 13 women with a mean age of 66 years. The indication for interposition graft placement was recurrent stenosis with inability to perform endarterectomy in nine operations, a severe kink or technical problem during endarterectomy in nine, aneurysmal changes of the artery in six, and thrombosis of the endarterectomy site segment with stroke in two. There were no perioperative deaths and no further perioperative neurologic complications. Follow-up with performance of yearly duplex scans was obtained in all patients, and the mean duration of follow-up was 36 months. One patient (4%) died of end-stage pulmonary disease during the study interval. Occlusion of the polytetrafluoroethylene graft occurred at 12 months in one patient (4%). Hemodynamically significant restenosis developed in two patients (8%), and two patients (8%) had mild restenosis. Evidence of a second restenosis developed in three of the nine patients who underwent polytetrafluoroethylene interposition graft placement for carotid restenosis. On the basis of our study results, we conclude that polytetrafluoroethylene can be used effectively for carotid reconstruction when an interposition graft is required. However, recurrent stenosis occurs. Patients who undergo polytetrafluoroethylene interposition graft placement for carotid restenosis appear to be at high risk for a second restenosis. PMID- 1404682 TI - Cerebrovascular magnetic resonance angiography: a critical verification. AB - Because simultaneous noninvasive noncontrast imaging of cervical and cerebral vasculature and brain is possible with magnetic resonance angiography (MRA) and imaging (MRI), the following study was undertaken from July 1990 to January 1992. One hundred twenty-eight patients were examined with General Electric 1.5 Tesla MRI systems. Axially acquired volumetric three-dimensional time-of-flight MRA with 0.7 mm3 voxel size with regional maximum intensity projection after processing followed a two-dimensional time-of-flight localizing sequence. These two MRA sequences combined with spin-echo parenchymal brain MRI were compared with duplex scans, contrast angiograms, and surgical findings. Blinded readings by a radiologist and vascular surgeon allowed comparison of grades of luminal diameter narrowing (normal, mild, moderate, severe, and occluded) seen on MRA to be compared with those of Doppler and contrast angiography. Excluding 12 nondiagnostically imaged internal carotid arteries (10 MRA) and limiting duplex correlation to within 5 days of the MRA examination allowed critical appraisal of 182 internal carotid arteries. Exact correlation of grade of stenosis was obtained by the radiologist in 136 (74.7%) of 182 arteries and the surgeon in 138 (75.8%) of 182 arteries. Spearman rank correlation analysis found rank correlation coefficients of 0.88 (p < 0.001) and 0.83 (p < 0.001), respectively, for the radiologist and vascular surgeon. Disagreement one category apart was found by the radiologist in 35 studies (19.3%) and the surgeon in 28 studies (15.4%). Two or more grades of disagreement were found by the radiologist in 11 studies (6%) and the surgeon in 16 studies (8.8%). Contrast angiogram-MRA agreement was found in 86% of 36 internal carotid arteries. The degree of stenosis detected by MRA was concordant with surgical findings in 39 of 40 patients. Thus MRA emerges as a useful and accurate method of obtaining cerebrovascular evaluation in clinical practice. PMID- 1404683 TI - Upper extremity arterial bypass distal to the wrist. AB - Seventeen arterial bypass procedures distal to the wrist have been performed in 13 men and two women at the Oregon Health Sciences University during the past 9 years. Ten patients had traumatic true or false aneurysms of the ulnar artery with digital embolization. Five patients with end-stage renal disease had severe hand and finger ischemia manifested by rest pain or digital ulceration resulting from widespread forearm and hand arterial occlusions. Patients with aneurysms of the ulnar artery underwent excision and reversed autogenous vein grafting (n = 11) from the distal ulnar artery in the forearm to the superficial palmar arch. All the patients with end-stage renal disease had severe occlusive disease of the forearm and hand arteries and underwent a variety of procedures including radial radial bypass (n = 2), ulnar-ulnar bypass (n = 2), radial-radial bypass with takedown of a Brescia-Cimino fistula (n = 1), and brachial-radial bypass (n = 1). High-quality upper extremity and magnification hand arteriography was essential for operative planning and was available on all patients. Distal saphenous vein from the ankle or foot was the graft source in 16 procedures and basilic vein the source in one procedure. All operations were performed with headlight illumination, optical loupes, fine sutures, and microvascular instruments. There were no operative deaths or major complications. The mean follow-up period was 14 months. Of the 17 grafts, 16 remained patent by clinical and vascular lab criteria. The single occlusion occurred in an ulnar aneurysm bypass and was accompanied only by mild intolerance to cold.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1404684 TI - Modified polytetrafluoroethylene: indium 111-labeled platelet deposition on carbon-lined and high-porosity polytetrafluoroethylene grafts. AB - Platelet accumulation on carbon-lined (CL) and high-porosity (HP) polytetrafluoroethylene (PTFE) grafts was investigated in vivo. In experiment 1, 20 CL grafts and 20 control PTFE grafts, each 5 cm in length and 4 mm in diameter, were interposed into both carotid and femoral arteries of 10 dogs. In experiment 2, 12 HP grafts (90 microns mean internodal distance) and 12 control PTFE grafts were implanted in six dogs. Indium 111-labeled platelets were injected intravenously and the grafts were retrieved 48 hours later. Radioactivity of the grafts and a control segment of the carotid artery was counted. A graft platelet accumulation index (GPAI) was calculated as the ratio of emission from the graft compared to that from the control segment. The GPAI of the CL graft was significantly less than the GPAI of the control graft in both the carotid (control 29.7 +/- 5.46, CL 22.3 +/- 6.55; n = 9 [p < 0.05]) and the femoral arteries (control 30.7 +/- 9.65, CL 22.0 +/- 6.59; n = 9 [p < 0.05]). There was no significant difference in GPAI between the control and HP grafts in the carotid arteries (control 30.6 +/- 11.8, HP 31.5 +/- 9.71; n = 6) and in the femoral arteries (control 31.5 +/- 7.88, HP 34.0 +/- 4.97; n = 6). Carbon lining decreases platelet accumulation on PTFE grafts in the early postoperative period, and HP grafts do not exhibit increased platelet uptake. PMID- 1404685 TI - Ruptured abdominal aortic aneurysms: a new perspective. PMID- 1404686 TI - Inflammatory abdominal aortic aneurysm and the associated T cell reaction: a case study. PMID- 1404687 TI - Delayed postoperative bleeding from polytetrafluoroethylene carotid artery patches. PMID- 1404688 TI - A case of nutcracker syndrome: treatment by mesoaortic transposition. PMID- 1404690 TI - Women's health specialty, other issues on agenda of 'reframing' conference. PMID- 1404689 TI - Aneurysms and experimental atherosclerosis. PMID- 1404692 TI - Women's health action plan sees first anniversary. PMID- 1404693 TI - Antibodies to silicone detected in patients with severe inflammatory reactions. PMID- 1404691 TI - Specific HIV-related problems of women gain more attention at a price--affecting more women. PMID- 1404695 TI - NIH researchers get retraining assistance. PMID- 1404694 TI - First clinical study of breast implants launched. PMID- 1404696 TI - From the Food and Drug Administration. PMID- 1404697 TI - From the Centers for Disease Control. Pregnancy risks determined from birth certificate data--United States, 1989. PMID- 1404698 TI - From the Centers for Disease Control. Ectopic pregnancy--United States, 1988 1989. PMID- 1404699 TI - From the Centers for Disease Control. Surgical sterilization among women and use of condoms--Baltimore, 1989-1990. PMID- 1404700 TI - From the Centers for Disease Control. FDA approval of second diphtheria, tetanus toxoids, and acellular pertussis vaccine. PMID- 1404701 TI - From the Centers for Disease Control. Trends in ischemic heart disease mortality- United States, 1980-1988. PMID- 1404702 TI - From the Center for Disease Control. Rapid health needs assessment following Hurricane Andrew--Florida and Louisiana, 1992. PMID- 1404703 TI - From the Centers for Disease Control. International Task Force for Disease Eradication. PMID- 1404704 TI - From the Centers for Disease Control. Tobacco, alcohol, and other drug use among high school students--United States, 1991. PMID- 1404705 TI - Female-to-male transmission of HIV. PMID- 1404706 TI - Female-to-male transmission of HIV. PMID- 1404707 TI - Weighing the risk factors in coronary artery bypass surgery. PMID- 1404708 TI - Coffee and plasma lipid levels. PMID- 1404709 TI - Diagnosis of brain death and organ donation. PMID- 1404710 TI - Near death in twins, reported 22 years ago. PMID- 1404711 TI - A population-based twin study of alcoholism in women. AB - OBJECTIVE: To clarify the role of genetic factors in the etiology of alcoholism in women. DESIGN AND SETTING: Personal structured psychiatric interviews conducted by researchers "blinded" to the status of the co-twin in an epidemiologic sample of 1030 female-female twin pairs of known zygosity from the population-based Virginia Twin Registry. MEASURES: Three definitions of lifetime prevalence of alcoholism based on Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria: (1) alcoholism with tolerance or dependence; (2) alcoholism with or without tolerance-dependence; and (3) alcoholism with or without tolerance-dependence or problem drinking. RESULTS: Using narrow, intermediate, or broad definitions, the probandwise concordance for alcoholism was consistently higher in monozygotic than in dizygotic twin pairs. Multifactorial threshold models suggested that the heritability of liability to alcoholism in women is in the range of 50% to 60%. CONCLUSIONS: The results support the hypothesis that genetic factors play a major role in the etiology of alcoholism in women. Women should be well represented in the efforts currently under way to elucidate the molecular basis of the genetic susceptibility to alcoholism. PMID- 1404712 TI - Differences in quality of care for hospitalized elderly men and women. AB - OBJECTIVE: To analyze whether important gender differences exist in the quality of hospital care provided to patients with four major medical conditions. DESIGN: Bivariate and multivariate comparisons of clinically detailed sickness at admission, quality, utilization, and outcome measures. SETTING: Acute care hospitals located in five states. PATIENTS OR OTHER PARTICIPANTS: A total of 11,242 patients 65 years or older who were hospitalized with one of four diseases: congestive heart failure, acute myocardial infarction, pneumonia, and cerebrovascular accident. We derived our data from the nationally representative sample used to study the quality of hospital care for Medicare patients before and after the implementation of the prospective payment system. A hierarchical (nested) cluster sampling design was used to draw disease-specific samples of patients hospitalized in 1981, 1982, 1985, or 1986 in one of 297 hospitals located in 30 areas within five states. INTERVENTIONS: This was an observational study. MAIN OUTCOME MEASURES: Sickness at admission, process, use rates, length of stay, discharge status, discharge destination, and mortality. RESULTS: Sex differences in sickness at admission varied by disease. There was some evidence that women received worse process of care, but the difference was very small. We found many similarities in the process and outcomes of care for male and female patients. CONCLUSIONS: After controlling for sickness at admission, age, and other important covariates, the in-hospital experiences of elderly men and women showed greater similarities than differences. The concern that sex bias enters into clinical decision making during hospitalization is eased, although not entirely eliminated. PMID- 1404713 TI - Environmental and familial contributions to insulin levels and change in insulin levels in middle-aged women. AB - OBJECTIVE: To examine familial and environmental variables associated with elevated insulin levels and changes in insulin levels in healthy, premenopausal women. METHODS: A population-based sample of 518 women (aged 42 to 50 years) completed baseline assessments of weight, cardiovascular risk factors, exercise behaviors, and glucose and insulin levels (fasting and 2 hours after a glucose load); 495 of the women were reevaluated after 3 years. RESULTS: Plasma insulin levels were related to weight, activity level, race, body fat distribution, and weight gain since age 20 years. Parental history of either diabetes or hypertension was also related to elevated insulin levels, independent of body mass index, with the highest insulin levels occurring in those women with a parental history of both diseases. Increases in plasma insulin levels over the years of follow-up were related to weight gain. CONCLUSIONS: This study suggests that importance of using family history to identify women who may have elevated insulin levels and of intervening to prevent weight gain during middle age. PMID- 1404714 TI - Age at onset for familial epithelial ovarian cancer. AB - OBJECTIVE: To provide age-specific risks for ovarian cancer for relatives of ovarian cancer case patients. To characterize the age at onset for ovarian cancer for women with a single relative vs several relatives affected with ovarian cancer. DESIGN: Three previous studies were reexamined. The cumulative probability of ovarian cancer in first-degree relatives of women with histologically confirmed epithelial ovarian cancer and matched control subjects who participated in the Cancer and Steroid Hormone (CASH) Study was determined. The age of onset of ovarian cancer in women with and without relatives with ovarian cancer in a Washington, DC, case-control study was contrasted with that of women with at least two first-degree relatives studied at the National Cancer Institute (NCI). RESULTS: The CASH Study data showed that first-degree relatives of women with ovarian cancer had an increased risk for ovarian cancer, especially at older ages, when compared with relatives of control subjects. However, the median age at onset was the same among women in the Washington, DC, study with and without an affected relative. Among the women with an extensive family history of ovarian cancer studied at the NCI, the age at onset was considerably younger (47 years) than is typical for this disease (59 years). Of these, 17% had been diagnosed as having primary ovarian cancer by age 40 years. CONCLUSIONS: Women who have one first-degree relative affected by ovarian cancer are at greater risk for ovarian cancer but not at an age earlier than the general population. The small proportion of women who have several affected relatives are, however, at a greater risk of early onset of ovarian cancer. Prophylactic oophorectomy may be reasonable for these women. PMID- 1404715 TI - The postmenopausal estrogen/breast cancer controversy. AB - OBJECTIVE: To provide an overview of the postmenopausal estrogen/breast cancer controversy emphasizing the sources of disagreement in the literature and their clinical and research implications. DATA SOURCE AND SELECTION: A MEDLINE search of the English-language literature and a review of bibliographies of meta analyses describing the association between postmenopausal estrogen use and breast cancer risk. DATA EXTRACTION: Twenty-four original articles and three meta analyses were reviewed. In addition, five studies that attempted to minimize detection bias were reviewed to assess the potential role of this bias on risk estimates. DATA SYNTHESIS: Among the original articles, risk estimates ranged from a protective to an adverse effect in women who ever used estrogens; no consistent quantitative effects of estrogens on breast cancer risk were found. In the meta-analyses, summary risk estimates were not significantly elevated in women who ever used estrogen. Findings from European-based studies may account for the increased risk associated with increasing duration of use reported in one meta-analysis. In studies that controlled for detection bias, risk estimates were 1 or less in the ever-used category; there was no consistent effect across other categories of use. CONCLUSION: These findings do not support an overall increased risk of breast cancer in women who ever used postmenopausal estrogens or a conclusive or consistent effect across other measures of use. Cross-national differences in estrogen use and inequalities in breast cancer detection between estrogen users and nonusers may account for the increased risk estimates reported in some studies. Newer estrogen and progestin-opposed regimens need to be evaluated further. PMID- 1404716 TI - Reperfusion and revascularization strategies for coronary artery disease in women. AB - OBJECTIVE: One third of all deaths in women in the United States each year are attributable to coronary heart disease. Gender differences exist in the course and management of patients with coronary heart disease. Few randomized trials have been conducted in women to evaluate effective therapeutic strategies. With the aim of developing rational approaches to women with coronary heart disease, we review gender-related outcomes with coronary revascularization and reperfusion therapies. DATA SOURCE: English-language journal articles and reviews on the subject of women with coronary heart disease or gender-specific responses to coronary heart disease management, from 1970 through 1992, identified through MEDLINE searching. STUDY SELECTION: Selected studies included only randomized controlled trials for topics related to thrombolysis, and articles considered to contribute significantly to the topic of women with coronary artery disease in the case of angioplasty and coronary artery bypass grafting. DATA EXTRACTION: Two reviewers participated in extracting the data with the aim of presenting a balanced and comprehensive review of the subject. DATA SYNTHESIS: Thrombolysis in acute myocardial infarction reduces mortality in men and women, although women may have a reduced mortality benefit compared with men. Angioplasty and the newer interventional devices result in greater procedural morbidity but similar if not better long-term outcomes in women. Women may have a greater mortality rate than men with coronary artery bypass surgery, although studies suggest that outcome after bypass surgery may depend more on coronary size and preoperative risk factors than on gender itself. CONCLUSIONS: The existence of gender differences in the course of coronary heart disease and response to revascularization and reperfusion strategies suggests the need for unique clinical approaches to the female patient with coronary heart disease and stresses the importance of developing randomized trials that enroll adequate numbers of women and that are designed to answer gender-specific questions. PMID- 1404717 TI - The premenstrual syndrome. New views. PMID- 1404718 TI - Factors affecting mammographic visualization of the breast after augmentation mammaplasty. AB - OBJECTIVE: To measure the effect of various parameters on mammographic visualization of the breast after augmentation mammaplasty. DESIGN: Preoperative and postoperative mammography was performed in patients undergoing augmentation mammaplasty. The area of breast tissue visualized on each film was measured. Changes in the area visualized were correlated with a variety of different parameters. SETTING: The Breast Center, Van Nuys, Calif, a free-standing multidisciplinary breast diagnostic and treatment facility. PATIENTS: The 68 women (126 breasts) represent a consecutive sample of patients undergoing augmentation mammaplasty for whom preoperative and postoperative mammograms were available. MAIN OUTCOME MEASURES: Area visualized was correlated with degree of capsular contracture, implant position, type of mammography, preoperative breast size, implant size, and implant type. RESULTS: The major factor affecting mammography is capsular contracture. Little or no capsular contracture results in a 30% reduction in the area visualized; moderate or severe contracture results in a 50% reduction. Other important factors include implant position (improved visualization with implant beneath pectoral muscle) and type of mammography performed (slightly more tissue seen with displacement technique). Very small preoperative breast size yields increased visualization. Implant size and type have little or no effect. CONCLUSIONS: In most women with breast implants, there is a decrease in measurable breast tissue on the postaugmentation mammogram. Capsular contracture and implant position exert a profound effect; type of mammography performed and preoperative breast size are also significant. PMID- 1404719 TI - American women's health care. A patchwork quilt with gaps. PMID- 1404720 TI - Women's health research. Prescribing change and addressing the issues. PMID- 1404721 TI - Diagnostic breast imaging. PMID- 1404722 TI - Oral steroid therapy for asthma and contact dermatitis. PMID- 1404723 TI - A few words of advice from a woman of letters--Ann Landers. PMID- 1404724 TI - Somalia's death toll underlines challenges of post-cold war world. PMID- 1404725 TI - Infants, science may lose as liability is blamed for company pullout from HIV prevention trial. PMID- 1404727 TI - From the Centers for Disease Control. Asthma--United States, 1980-1990. PMID- 1404726 TI - From the Congressional Office of Technology Assessment. PMID- 1404728 TI - From the Centers for Disease Control. HIV infection, syphilis, and tuberculosis screening among migrant farm workers--Florida, 1992. PMID- 1404729 TI - From the Centers for Disease Control. Imported dengue--United States, 1991. PMID- 1404730 TI - Disseminated sporotrichosis. PMID- 1404731 TI - National health care reform: the aura of inevitability intensifies. PMID- 1404732 TI - National health care reform: the aura of inevitability intensifies. PMID- 1404733 TI - The NASA syndrome revisited. PMID- 1404734 TI - Americans with Disabilities Act. PMID- 1404735 TI - Errors in prescribing methotrexate. PMID- 1404736 TI - Primary care and health: a cross-national comparison. PMID- 1404737 TI - Neonatal homicide following Roe v Wade. PMID- 1404738 TI - Neonatal homicide following Roe v Wade. PMID- 1404739 TI - Access to care for poor children: necessary but not sufficient. PMID- 1404740 TI - Change in body weight and longevity. AB - OBJECTIVE: To investigate the effect of body weight change on longevity. DESIGN: Cohort analytic study, following men from 1977 through 1988. SETTING: The study was conducted among Harvard University alumni with mean age of 58 years. PATIENTS: Alumni, free of cardiovascular disease and cancer, completed questionnaires on weight, height, cigarette habit, and physical activities in 1962 or 1966 and in 1977 (n = 11,703). We assessed weight change between questionnaires, based on self-reported weights. MAIN OUTCOME MEASURE: Mortality from all causes (n = 1441), coronary heart disease (n = 345), and cancer (n = 459), determined from death certificates. RESULTS: Lowest all-cause mortality was among alumni maintaining stable weight (+/- 1 kg). With this category as referent (relative risk = 1.00), relative risks of death associated with losing more than 5 kg, losing between 1 and 5 kg, (more than 1 kg and up to 5 kg) gaining between 1 and 5 kg (more than 1 kg and up to 5 kg), and gaining more than 5 kg were 1.57 (95% confidence interval, 1.34 to 1.84), 1.26 (1.10 to 1.46), 1.06 (0.90 to 1.24), and 1.36 (1.11 to 1.66), respectively. For coronary heart disease mortality, relative risks were 1.75 (1.26 to 2.43), 1.43 (1.05 to 1.93), 1.28 (0.91 to 1.80), and 2.01 (1.36 to 2.97), respectively. Weight change did not predict cancer mortality. Findings were not explained by cigarette habit, physical activity, or body mass index. We observed similar trends for follow-up between 1977 and 1982 and between 1983 and 1988. Those losing or gaining more weight also reported greater total lifetime weight loss, which may indicate weight cycling. CONCLUSIONS: Both body weight loss and weight gain are associated with significantly increased mortality from all causes and from coronary heart disease but not from cancer. PMID- 1404741 TI - Physicians' utilization and charges for outpatient diagnostic imaging in a Medicare population. AB - OBJECTIVES AND RATIONALE: For 10 common clinical presentations, we assessed differences in physicians' utilization of and charges for diagnostic imaging, depending on whether they performed imaging examinations in their offices (self referral) or referred their patients to radiologists (radiologist-referral). METHODS: Using previously developed methodologies, we generated episodes of medical care from an insurance claims database. Within each episode, we determined whether diagnostic imaging had been performed, and if so, whether by a self-referring physician or a radiologist. For each of the 10 clinical presentations, we compared the mean imaging frequency, mean imaging charges per episode of care, and mean imaging charges for diagnostic imaging attributable to self- and radiologist-referral. RESULTS: Depending on the clinical presentation, self-referral resulted in 1.7 to 7.7 times more frequent performance of imaging examinations than radiologist-referral (P < .01, all presentations). Within all physician specialties, self-referral uniformly led to significantly greater utilization of diagnostic imaging than radiologist-referral. Mean imaging charges per episode of medical care (calculated as the product of the frequency of utilization and mean imaging charges) were 1.6 to 6.2 times greater for self referral than for radiologist-referral (P < .01, all presentations). When imaging examinations were performed--including those performed in both physicians' offices and hospital outpatient departments--mean imaging charges were significantly greater for radiologists than for self-referring physicians in seven of the clinical presentations (P < .01). This result is related to the high technical charges of hospital outpatient departments; in office practice, radiologists' mean charges for imaging examinations were significantly less than those of self-referring physicians for seven clinical presentations (P < .01). CONCLUSIONS: Nonradiologist physicians who operate diagnostic imaging equipment in their offices perform imaging examinations more frequently, resulting in higher imaging charges per episode of medical care. These results extend our previous research on this subject by their focus on a broader range of clinical presentations; a mostly elderly, retired population; and the inclusion of higher technology imaging examinations. PMID- 1404742 TI - Physician ownership of physical therapy services. Effects on charges, utilization, profits, and service characteristics. AB - OBJECTIVE: To evaluate the effects of physician ownership of freestanding physical therapy and rehabilitation facilities on utilization, charges, profits, and three measures of service characteristics for physical therapy treatments. DESIGN: Statistical comparison by physician joint venture ownership status of freestanding physical therapy and comprehensive rehabilitation facilities providing physical therapy treatments in Florida. PARTICIPANTS: A total of 118 outpatient physical therapy facilities and 63 outpatient comprehensive rehabilitation facilities providing services in Florida during 1989. The data from the facilities were collected under a legislative mandate. MAIN OUTCOME MEASURES: Visits per patient, average revenue per patient, percent operating income, percent markup, profits per patient, licensed therapist time per visit, and licensed and nonlicensed medical worker time per visit. RESULTS: Visits per patient were 39% to 45% higher in joint venture facilities. Both gross and net revenue per patient were 30% to 40% higher in facilities owned by referring physicians. Percent operating income and percent markup were significantly higher in joint venture physical therapy and rehabilitation facilities. Licensed physical therapists and licensed therapist assistants employed in non-joint venture facilities spend about 60% more time per visit treating physical therapy patients than licensed therapists and licensed therapist assistants working in joint venture facilities. Joint ventures also generate more of their revenues from patients with well-paying insurance. CONCLUSION: Our results indicate that utilization, charges per patient, and profits are higher when physical therapy and rehabilitation facilities are owned by referring physicians. With respect to service characteristics, joint venture firms employ proportionately fewer licensed therapists and licensed therapist assistants to perform physical therapy, so that licensed professionals employed in joint venture businesses spend significantly less time per visit treating patients. These results should be of interest to the medical profession, third-party payers, and policymakers, all of whom are concerned about the consequences of physician self-referral arrangements. PMID- 1404743 TI - The crisis in primary care and the role of medical schools. Defining the issues. AB - While a number of issues have diminished the attractiveness of primary care residency programs to USGs, the absolute number of residents in these programs has increased rather than diminished over the past decade, although the proportion of USGs choosing these fields has decreased. In the current arena of medical practice, there are many reasons why these fields are not among the most attractive, and there are several remedies that could be applied to increase their attractiveness. Focusing on medical schools as the sole cause of this dilemma, however, is the least effective way of accomplishing this objective; in addition, this will allow those truly able to increase interest in these fields, such as state and federal governments, to have a reason for not doing so. As long as the medical marketplace is sufficiently large enough to accommodate more than the number of graduates from US medical schools in "desirable" residency training positions, one can never effectively "force" a choice of residency training, nor should one. Primary care can be among the most rewarding of specialties, if adequately supported. It is this support that is lacking and must be addressed. PMID- 1404744 TI - Risk of suicide among persons with AIDS. A national assessment. AB - OBJECTIVE: We sought to describe the rate, risk, trends, methods, and distribution of suicide among persons with the acquired immunodeficiency syndrome (AIDS) in the United States. DESIGN: We used National Center for Health Statistics multiple-cause mortality data from 1987 through 1989 to identify suicides among persons with AIDS (PWAs) and public-access AIDS surveillance data to determine person-years of observation of PWAs. PATIENTS: Residents of the United States with death certificates indicating suicide. MAIN OUTCOME MEASURE: Death certificates indicating both AIDS and suicide. RESULTS: In 1987 through 1989, a total of 165 suicides among PWAs occurred in 45 states and the District of Columbia. All but one case were male. Among males the rate was 165 per 100,000 person-years of observation, 7.4-fold higher than among demographically similar men in the general population. Self-poisoning with drugs was both the most common method (35%) and the method with the highest standardized mortality ratio (35). Suicide risk for PWAs decreased significantly (P < .05) from 1987 to 1989. CONCLUSION: Persons with AIDS have an increased risk of suicide, and assessment of such risk should be a standard practice in their care. These assessments should be carefully considered when potentially lethal medications are prescribed. The declining trend in suicide rates between 1987 and 1989 is encouraging; possible causes include emerging therapies for human immunodeficiency virus/AIDS, better psychiatric care for these patients, and lessened social stigma against PWAs. PMID- 1404745 TI - Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. AB - The Jones Criteria for guidance in the diagnosis of acute rheumatic fever were first published by T. Duckett Jones, MD, in 1944 and have been revised over the years by the American Heart Association. The current guidelines are an update of these criteria. For the first time, the guidelines are designed to establish the initial attack of acute rheumatic fever. Major manifestations, minor manifestations, and supporting evidence of antecedent group A streptococcal infection are discussed. These updated guidelines expand on the available tools to diagnose streptococcal pharyngitis and clarify the available antibody tests for detecting antecedent group A streptococcal infection. At the present time echocardiography without accompanying auscultatory findings is insufficient to be the sole criterion for valvulitis in acute rheumatic fever. Finally, this article addresses overdiagnosis of rheumatic fever and lists exceptions to the Jones Criteria, including recurrent attacks in individuals with a history of rheumatic fever. PMID- 1404746 TI - Not myositis. A series of chance encounters. PMID- 1404747 TI - The myth of the abortion trauma syndrome. PMID- 1404748 TI - High-fat diets and breast cancer risk. The epidemiologic evidence. PMID- 1404749 TI - The American health care system and the 1992 election. PMID- 1404750 TI - A piece of my mind. No better or wiser, just braver and sicker. PMID- 1404751 TI - 'Basic benefits' have many variations, tend to become political issues. PMID- 1404752 TI - Using high-quality providers to cope with today's rising health care costs. PMID- 1404753 TI - From the Centers for Disease Control. Pneumonic plague--Arizona, 1992. PMID- 1404754 TI - From the Centers for Disease Control. HIV counseling and testing services, public and private providers--United States, 1990. PMID- 1404755 TI - From the Centers for Disease Control. Tetanus--Rutland County, Vermont, 1992. PMID- 1404756 TI - From the Centers for Disease Control. Elevated blood lead levels in adults- United States, second quarter, 1992. PMID- 1404757 TI - The rational clinical examination. PMID- 1404758 TI - The rational clinical examination. PMID- 1404760 TI - The rational clinical examination. PMID- 1404759 TI - The rational clinical examination. PMID- 1404761 TI - The Academic Medical Center and the health of the public. PMID- 1404762 TI - The Academic Medical Center and the health of the public. PMID- 1404763 TI - The magical medical media tour. PMID- 1404764 TI - The magical medical media tour. PMID- 1404765 TI - Deaths from asbestos: one physician's practice. PMID- 1404766 TI - Potential dangers of alcohol-based sunscreens. PMID- 1404767 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part I. Introduction. PMID- 1404768 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part II. Adult basic life support. PMID- 1404769 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part III. Adult advanced cardiac life support. PMID- 1404770 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part IV. Special resuscitation situations. PMID- 1404771 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part V. Pediatric basic life support. PMID- 1404772 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part VI. Pediatric advanced life support. PMID- 1404773 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part VII. Neonatal resuscitation. PMID- 1404774 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part VIII. Ethical considerations in resuscitation. PMID- 1404775 TI - Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part IX. Ensuring effectiveness of communitywide emergency cardiac care. AB - Cardiac arrest treatment continues to evolve. Adequate treatment of the individual patient requires that the whole ECC system function smoothly, consistently, and rapidly. To maximize communitywide survival rates, a careful evaluation of the entire chain of survival is required using standard measurements of performance. The challenge for the next decade is to establish this infrastructure and to conduct multicenter, prospective, controlled clinical trials to better define the key factors that will improve survival of cardiac arrest in every community. PMID- 1404776 TI - Emergency cardiac care. The science behind the art. PMID- 1404777 TI - The issue of CPR. PMID- 1404778 TI - Creighton University marks centennial. PMID- 1404779 TI - Family tree can yield lifesaving knowledge for patients at risk for hereditary cancers. PMID- 1404780 TI - Students challenged to make ethics part of their 'habit of thought'. PMID- 1404782 TI - Medical students take the ideal of service to new heights in the Dominican Republic. PMID- 1404781 TI - An ethicist's perspective on health care reform. PMID- 1404783 TI - Research turns to perhaps overlooked osteocytes in efforts to find answers to osteogenesis puzzle. PMID- 1404784 TI - Longitudinal study pursues questions of calcium, hormones, and metabolism in life of skeleton. PMID- 1404785 TI - From the Centers for Disease Control. Influenza vaccination levels, 1989-1991. PMID- 1404786 TI - A piece of my mind. A 'nonworkloaded' task. PMID- 1404787 TI - The self-reporting of cocaine use. PMID- 1404788 TI - The self-reporting of cocaine use. PMID- 1404789 TI - The self-reporting of cocaine use. PMID- 1404790 TI - The self-reporting of cocaine use. PMID- 1404791 TI - Drug testing and the toilet bowl blues. PMID- 1404792 TI - Reporting abuse of competent patients. PMID- 1404793 TI - Environmental tobacco smoke and heart disease: a correction. PMID- 1404794 TI - Socioeconomic status and risk for substandard medical care. AB - OBJECTIVE: To assess whether the socioeconomic status of the patient was associated with the risk of adverse events, defined as medical injuries caused by medical management, and the proportion of these events that resulted from substandard care. SETTING: 51 hospitals in New York State. METHODS: Rates of medical injury and substandard care by gender, race, income, and payer status were developed from reviews of 30,195 medical records in New York in 1984. We evaluated these socioeconomic parameters in a multivariate analysis, while controlling for hospital-level factors. RESULTS: We found that uninsured patients (odds ratio, 2.35; 95% confidence interval, 1.40 to 3.95) were at greater risk for substandard care. The characteristics of the hospitals to which patients were admitted did not affect this result. Race, gender, and income were not independently associated with risk for medical injury or substandard care in multivariate analyses. CONCLUSION: Our findings suggest that the uninsured are at greater risk for suffering medical injury due to substandard medical care. PMID- 1404795 TI - Rates of avoidable hospitalization by insurance status in Massachusetts and Maryland. AB - OBJECTIVE: To determine whether uninsured and Medicaid patients have higher rates of avoidable hospitalizations than do insured patients. DESIGN: We used 1987 computerized hospital discharge data to select a cross-sectional sample of hospitalized patients. Population estimates from the Current Population Survey were used to estimate rates of admission, standardized for age and sex. SETTING: Nonfederal acute care hospitals in Massachusetts and Maryland. PATIENTS: All patients under 65 years of age who were uninsured, privately insured, or insured by Medicaid. Hospitalizations for obstetric and psychiatric conditions were excluded. MAIN OUTCOME MEASURES: Relative risk of admission for 12 avoidable hospital conditions (AHCs) identified by a physician panel. RESULTS: Uninsured and Medicaid patients were more likely than insured patients to be hospitalized for AHCs. Rates for uninsured patients were significantly greater than for privately insured patients in Massachusetts for 10 of 12 individual AHCs, and in Maryland for five of 12 AHCs. After adjustment for baseline utilization, the results were statistically significant for 10 of 12 AHCs in Massachusetts and seven of 12 AHCs in Maryland. For Medicaid patients, rates were significantly greater than for privately insured patients for all AHCs in each state before adjustment, and for nine of 12 and seven of 12 AHCs in each state, respectively, after adjustment for baseline utilization. CONCLUSION: Our findings suggest that patients who are uninsured or who have Medicaid coverage have higher rates of hospitalization for conditions that can often be treated out of hospital or avoided altogether. Our approach is potentially useful for routine monitoring of access and quality of care for selected groups of patients. PMID- 1404796 TI - Magnesium administration and dysrhythmias after cardiac surgery. A placebo controlled, double-blind, randomized trial. AB - OBJECTIVE: To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: A tertiary acute-care 500-bed university teaching hospital. PATIENTS: Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied. INTERVENTIONS: Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass. RESULTS: Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia. CONCLUSIONS: Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period. PMID- 1404797 TI - Bone gain in young adult women. AB - OBJECTIVE: To test whether bone mass increases in healthy nonpregnant white women during early adult life after cessation of linear growth; and to test whether various self-chosen levels of physical activity and nutrient intake or use of oral contraceptives influences this increase in bone mass. DESIGN: Longitudinal prospective study of up to 5 years of 156 healthy college-aged women full-time students attending professional schools in universities in the Omaha, Neb, area. SETTING: University medical center. PARTICIPANTS: A convenience sample of healthy women students from Omaha-area professional schools. Any candidate with an illness, condition, or medication (except oral contraceptives) thought to affect general health or bone mass was excluded. INTERVENTIONS: None. OUTCOME MEASURES: Clinical and family histories of disease, particularly osteoporosis; oral contraceptive use; bone mineral densities of the spine, forearm, and total body by dual- and single-photon absorptiometry; estimates of nutrient intake by repeated 7-day diet diaries; and measures of physical activity using a physical activity monitor. RESULTS: The median gain in bone mass for the third decade of life, expressed as a percentage per decade, was 4.8% for the forearm, 5.9% for lumbar bone mineral content, 6.8% for lumbar bone mineral density, and 12.5% for total body bone mass (P < .0001 in all cases). By both bivariate and multiple regression analysis the rate of gain in bone density of the spine was negatively correlated with age and positively correlated with calcium/protein intake ratio and physical activity (multiple r = .31; P = .004). Bivariate analysis showed that use of oral contraceptives was associated with greater gain in total body bone mass (r = .31, P = .01). The estimated age when mineral acquisition ceased ranged from 28.3 years to 29.5 years at the several study sites. CONCLUSIONS: Gain in bone mass occurs in healthy young women during the third decade of life. Physical activity and dietary calcium intake both exert a positive effect on this bone gain. Use of oral contraceptives exerts a further independent positive effect. Changes in life-style among college-aged women, involving relatively modest increases in physical activity and calcium intake, may significantly reduce the risk of osteoporosis late in life. PMID- 1404798 TI - Ethical values at stake in health care reform. PMID- 1404799 TI - Familial Creutzfeldt-Jakob disease (codon 200 mutation) with supranuclear palsy. AB - OBJECTIVE: To identify a possible gene defect in a large kindred with atypical Creutzfeldt-Jakob disease (CJD). SUBJECTS: Over 360 kindred members, with and without progressive dementia. METHODS: Family, hospital, and clinic records were reviewed. The DNA was extracted from paraffin-embedded brain tissue of two deceased patients, and from blood leukocytes of nine healthy persons at risk. DNA was subjected to polymerase chain reaction and then analyzed by restriction endonuclease and single nucleotide primer extension. RESULTS: Nine family members had progressive fatal neurological disease consistent with CJD without myoclonus or typical electroencephalographic findings. Supranuclear gaze palsy was present in all five patients who underwent eye examinations. Two neuropathologically confirmed cases and five of nine at-risk family members had an identical mutation (GAG to AAG, glutamic acid to lysine) in codon 200 of the amyloid gene (PRNP) on chromosome 20. CONCLUSIONS: Clinically atypical CJD with early supranuclear gaze palsy but without myoclonus or characteristic electroencephalographic periodicity patterns is associated with the codon 200Lys mutation in the largest CJD kindred yet reported. The clinical concept of familial CJD should be enlarged to include this unusual phenotype. PMID- 1404800 TI - Gene therapy for cancer. PMID- 1404801 TI - Evidence-based medicine. A new approach to teaching the practice of medicine. PMID- 1404803 TI - Call for papers on medical education. PMID- 1404802 TI - America's safety net. The wrong place at the wrong time? PMID- 1404804 TI - Playing favorites with patients. PMID- 1404805 TI - Attitudes and discourse: the words of medicine. PMID- 1404806 TI - How to create and maintain an article file. PMID- 1404807 TI - 'Don't get too comfortable'. PMID- 1404808 TI - At third meeting, menopause experts make the most of insufficient data. PMID- 1404809 TI - Is 'male menopause' real or just an excuse? PMID- 1404810 TI - From the Centers for Disease Control. Behaviors related to unintentional, intentional injuries, high school students--United States, 1991. PMID- 1404811 TI - From the Centers for Disease Control. Lead ingestion, ceramic glaze--Alaska, 1992. PMID- 1404812 TI - The kappa statistic. PMID- 1404813 TI - The Los Angeles riots of 2014: how to avert them. PMID- 1404814 TI - Transparent polyurethane film as a catheter dressing. PMID- 1404815 TI - T-lymphocyte subsets in intravenous drug users with HIV-1 infection. PMID- 1404816 TI - T-lymphocyte subsets in intravenous drug users with HIV-1 infection. PMID- 1404817 TI - The spectrum of intent in fatal child abuse. PMID- 1404818 TI - Helmets for motor cyclists: lower fatal head injury rate but more crashes mean more study. PMID- 1404819 TI - A controlled trial of tacrine in Alzheimer's disease. The Tacrine Study Group. AB - OBJECTIVE: To compare efficacy and safety of tacrine hydrochloride with placebo in patients with probable Alzheimer's disease. DESIGN: A 12-week, double-blind, placebo-controlled, parallel-group study. SETTING: Outpatients at 23 centers. PATIENTS: Men and women with probable Alzheimer's disease, at least 50 years old, mildly to moderately impaired, without other significant medical conditions. INTERVENTIONS: In the initial 6 weeks, patients received placebo, 20 mg/d of tacrine, or 40 mg/d of tacrine. In the second 6 weeks, half received the same treatment and half increased tacrine dose: those receiving placebo increased to 20 mg/d, those receiving 20 mg/d increased to 40 mg/d, and those receiving 40 mg/d increased to 80 mg/d. PRIMARY OUTCOME MEASURES: Alzheimer's Disease Assessment Scale (ADAS) cognitive component and clinician-rated Clinical Global Impression of Change (CGIC). RESULTS: Four hundred sixty-eight patients entered. After 12 weeks, dose-related improvement was significant on the ADAS cognitive (P = .014), clinician-rated CGIC (P = .014), and caregiver-rated CGIC (P = .006). Comparison of 80 mg/d with placebo showed significant improvement on the ADAS cognitive (P = .015), clinician-rated CGIC (P = .016), and caregiver-rated CGIC (P = .028). Significant effects appeared as early as 6 weeks on the ADAS cognitive and caregiver-rated CGIC. Among patients receiving 80 mg/d of tacrine, 51% achieved a four-point or greater improvement of the ADAS cognitive component after 12 weeks of treatment. Reversible asymptomatic transaminase elevations greater than three times normal occurred in 25% of patients. Other treatment related events included nausea and/or vomiting (8%), diarrhea (5%), abdominal pain (4%), dyspepsia (3%), and rash (3%). CONCLUSIONS: These results confirm the efficacy and safety of tacrine in some patients with Alzheimer's disease. After 12 weeks, the magnitude of the treatment effect is clinically important and recognized by the physician and caregiver. Liver toxicity is reversible and easily detected by weekly alanine aminotransferase determinations. PMID- 1404820 TI - Acute myocardial infarction in the Medicare population. Process of care and clinical outcomes. AB - OBJECTIVE: To describe the process of care and clinical outcomes associated with acute myocardial infarction (AMI) in the Medicare population, and to examine differences in process of care and outcome of care as a function of patient age, gender, and race. DESIGN: Retrospective cohort study using a longitudinal database created from Medicare utilization and administrative files. PATIENT POPULATIONS: A cohort of AMI patients covered by Medicare in 1987 and a random sample of Medicare patients without AMI. MAIN PROCESS AND OUTCOME MEASUREMENTS: (1) The use of coronary angiography, coronary artery bypass graft surgery, and percutaneous transluminal coronary angioplasty during the first 90 days after a new AMI; (2) mortality at 30 days, 1 year, and 2 years; (3) reinfarction rates; and (4) reoperation rates for coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. MAIN RESULTS: Mortality rates were high: 26% at 30 days, 40% at 1 year, and 47% at 2 years. They varied greatly by age, less so by gender and race, and were high even among patients who survived the first 30 days. Compared with mortality, reinfarction was uncommon, occurring in 7.3% of patients. During the first 90 days, 23% of all patients underwent angiography and 13% underwent coronary revascularization (coronary artery bypass graft surgery, 8%; percutaneous transluminal coronary angioplasty, 5%). The use of all three procedures decreased with age and was less common among women and blacks than among men and whites. Differential use by age and race was greater for angiography than for revascularization procedures. CONCLUSIONS: The prognosis following AMI in patients aged 65 years and above is much worse than is commonly realized. Procedure use in these patients varies as a function of gender and race, even though mortality does not. Further research is needed to reduce the mortality of elderly patients with AMI and to understand the significance of differences in procedure use on the basis of sociodemographic characteristics. PMID- 1404821 TI - Results of a second-opinion trial among patients recommended for coronary angiography. AB - OBJECTIVE: To assess the feasibility of carrying out a second-opinion trial for patients urged to undergo coronary angiography and to assess the long-range outcome of such patients denied that procedure, and the criteria evolved for reaching such a conclusion. DESIGN: A case series of patients referred for a second opinion as to the need for coronary angiography. Patients were followed up by questionnaire, telephone call, and center visits. SETTING: Cardiovascular referral center and teaching hospital in Boston, Mass. PATIENTS: One hundred seventy-one patients with coronary artery disease (144 men, average age 60 years; range, 36 to 88 years). Three patients became unavailable for follow-up during a mean of 46.5 months. OUTCOME MEASURES: Concordant-discordant outcome as to the second opinion, cardiac events, invasive interventions, quality of life questionnaire, and level of symptoms. RESULTS: One hundred thirty-four (80%) of the 168 patients were judged not to require angiography; it was recommended in six. In 28 (16%) recommendation was deferred pending further studies. At a mean follow-up of 46.5 months among the 168 patients, there were seven cardiac deaths (annualized cardiac mortality of 1.1%); 19 patients experienced a new myocardial infarction (2.7% annualized rate), while 27 patients (4.3%) were judged to have developed unstable angina. Twenty-six patients (15.4%) ultimately underwent either coronary bypass or angioplasty. CONCLUSIONS: In a large fraction of medically stable patients with coronary disease who are urged to undergo coronary angiography, the procedure can be safely deferred. While there may be a limitation in terms of generalizing this experience to all patients with coronary disease, we reasonably conclude that an estimated 50% of coronary angiography currently being undertaken in the United States is unnecessary, or at least could be postponed. PMID- 1404822 TI - Health progress in the United States. Results of the 1990 objectives for the nation. PMID- 1404823 TI - Evaluation and management of the patient with syncope. AB - OBJECTIVE: To review the studies on diagnostic evaluation of syncope and to provide an approach to the diagnostic testing and management of this condition. DATA SOURCE: Published studies on the evaluation of syncope in the English language. STUDY SELECTION: Cohort studies and case series of patients presenting with syncope and focused studies of various diagnostic tests such as prolonged electrocardiographic monitoring, electrophysiologic studies, and upright tilt testing. Specific selection criteria were used in the case of prolonged electrocardiographic monitoring, in which all studies had to have performed at least 12 hours of monitoring. DATA EXTRACTION: Studies reviewed by the author. DATA SYNTHESIS: Studies in the 1980s have shown that a cause of syncope is not diagnosed in as many as 47% of the patients presenting with this symptom. When a cause of syncope is established, a history and physical examination lead to the identification of 56% to 85% of the causes. In the remaining patients, arrhythmia detection is a central issue. A major problem with the use of ambulatory electrocardiographic (Holter) monitoring in the diagnosis of arrhythmias is that symptomatic correlation with arrhythmias is rarely found (only 4% of patients). Increasing the duration of monitoring from 24 to 72 hours does not lead to increased yield of symptomatic arrhythmias. Patient-activated intermittent loop recorders that can be worn for several weeks may occasionally show a symptomatic correlation, but they are most useful in patients with multiple recurrences of syncope. Electrophysiologic studies are more likely to be abnormal in patients with underlying heart disease or those who have abnormalities on surface electrocardiogram. The most common abnormality found on electrophysiologic studies is inducible ventricular tachycardia. Upright tilt testing has been used to induce vasovagal syncope in patients with syncope of unknown cause. A positive response has been found in 26% to 87% of patients undergoing this type of testing. The specificity of this test needs to be further investigated. In patients with recurrent syncope of unknown cause, psychiatric evaluation should also be pursued for illnesses such as generalized anxiety disorder, panic disorder, somatization, and major depression. CONCLUSIONS: A directed approach to the evaluation is possible using the studies on diagnostic testing of syncope. PMID- 1404825 TI - Tacrine for treating Alzheimer's disease. PMID- 1404824 TI - What are we teaching about indigent patients? PMID- 1404826 TI - Chronic cough in children. PMID- 1404827 TI - Clinical decision making: from theory to practice. Applying cost-effectiveness analysis. The inside story. PMID- 1404828 TI - Cholera. PMID- 1404829 TI - Pattern of leucocyte acid phosphatase reaction in T-cell lymphoblastic leukaemia. AB - Acid phosphatase (AP) reaction is a specific cytochemical marker for T-cell lymphoblastic leukaemia (T-ALL). Twenty six cases of ALL were diagnosed as T-ALL employing cytochemical profiles including AP and sheep red blood cell rosettes. Three district patterns of AP reaction were observed. On one end of the spectrum, 100% of the positive blasts showed the classical dot-like reaction while on the other 100% showed a scattered reaction. Between the two a mixed pattern was observed with 30-80% of the positive blasts showing the dot-like reaction while the rest showed scattered pattern. Dot-like pattern showed L1 morphology, high counts and low SRBC rosettes while scattered showed L2 morphology, low counts and high SRBC rosettes. The pattern observed in our series differs from the dot-like reaction observed in T-ALL in the western series. We recommend that this pattern must be borne in mind when employing AP reaction for T-ALL diagnosis (JPMA 42: 151, 1992). PMID- 1404831 TI - Anorectal melanoma in northern Pakistan. AB - Melanoma of the anorectum is a rare malignancy. At Armed Forces Institute of Pathology (AFIP), 11 cases were diagnosed over a 10 year period (1981-1990) constituting 14.2% of all primary malignant melanomas. The anorectum was the commonest site for noncutaneous melanomas (45.8%). The age group commonly affected was the fifth to seventh decade (72.7%). Most of the tumours were extensive involving both anal canal and rectum. The proportion of anorectal melanoma is much higher in our study as compared to western reports (0.4-1.6%). The distribution of noncutaneous melanomas in our population also differs, with a relatively lower proportion of ocular melanomas (33.3%) which are the commonest (80%) in western studies (JPMA 42: 155, 1992). PMID- 1404830 TI - Management of uric acid stone. AB - Uric acid stones are the most readily dissolvable of all types of urinary stones. By maintaining urinary pH between 6.2-6.8 with the use of sodium acid citrate or uralyt-U and reducing serum uric acid by allopurinol, we tried to dissolve 107 stones in 67 patients. Ninety three (86.9%) stones were dissolved and 6 (5.6%) passed spontaneously within a period of one year. Eight (7.5%) stones were removed surgically or with ESWL. Five (7.5%) patients had stone recurrence over a period of 3 years follow-up. Serum uric acid was raised in 19 (28.5%) and urinary uric acid in 12 (18%) patients while urinary pH was low in 46 (69%) patients. For uncomplicated uric acid stones oral chemolysis on an out-patient basis is the treatment of choice. It is simple, safe and inexpensive. However, it requires rigid compliance by the patient and strict follow-up by ultrasonography (JPMA 42: 153, 1992). PMID- 1404832 TI - Immunoglobulin classes G,A,M in brain tumours. AB - Serum of 37 brain tumour patients was studied for, Total protein, Protein electrophoresis, IgG, IgA, and IgM in an attempt to ascertain humoral immune response. Findings were compared with 20 healthy subjects, matched for age, sex and socioeconomic status. There was significant rise in alpha-II globulin, while IgG was suppressed in tumour patients. Decrease of IgG was more marked in patients with malignant tumours. Immunoglobulin A was low in children when compared with adults. Immunoglobulin M remained unchanged (JPMA 42: 157, 1992). PMID- 1404833 TI - Sclerotherapy with aqueous phenol for outpatient treatment of hydrocoele and epididymal cysts. PMID- 1404834 TI - Leprosy in Karachi. PMID- 1404835 TI - Haemoglobin, haematocrit and plasma fibrinogen in cigarette smokers. PMID- 1404836 TI - Renal angiomyolipoma: an uncommon tumour. PMID- 1404837 TI - Incomplete testicular feminization syndrome. PMID- 1404838 TI - Polycystic kidney disease associated with pregnancy. PMID- 1404839 TI - Surgical management of carotid artery disease--an Irish experience. PMID- 1404840 TI - How to insert a pulmonary artery floatation catheter. PMID- 1404841 TI - Cryptosporidiosis in Karachi. PMID- 1404843 TI - Screening of children with arrhythmias for arrhythmia development during diving and swimming--face immersion as a substitute for diving and exercise stress testing as a substitute for swimming. AB - We compared face immersion and exercise stress testing by diving and swimming as screening methods for arrhythmias induced by immersion in water. The subjects were 64 children with various arrhythmias who were tested using 5 methods: diving, swimming, face immersion in 25 degrees C water, face immersion in 6 degrees C water, and a treadmill exercise test. Significant arrhythmias occurred during diving or swimming in 51 children, with 44 developing arrhythmias while diving. Both tachyarrhythmias and bradyarrhythmias were seen during diving, but 17 children who also showed significant arrhythmias while swimming mostly had tachyarrhythmias. A comparison with the incidence of arrhythmias produced by diving showed that face immersion in cold water had a sensitivity of 88.6%, a specificity of 85.0%, a predictive value of 92.9%, and an accuracy of 87.5%. Arrhythmias were alleviated in 12.5%, unchanged in 79.7%, and aggravated in 7.8% of the subjects. Face immersion thus appeared to be a useful and adequate screening substitute for diving. Exercise testing was also compared with swimming (sensitivity, 52.9%; specificity, 100%; predictive value, 100%; and accuracy, 87.5%). Arrhythmias were alleviated in 12.5% and unchanged in 87.5% of patients. Although exercise testing produced many false-negatives, all of the severe arrhythmias were reproduced. PMID- 1404842 TI - Emergency coronary angioplasty for acute myocardial infarction--factors affecting acute restenosis in catheterization laboratory and reocclusion during hospitalization. AB - A total of 107 consecutive patients with acute myocardial infarction underwent emergency coronary angioplasty (PTCA). Restoration of blood flow with TIMI grade III was established by emergency PTCA in 101 patients (94.4%). "Acute restenosis" was defined as a lesion that, when dilated to less than 50%, narrowed again to more than 75% luminar reduction 5 min after the balloon inflation. Acute restenosis occurred in 39 patients (39%). Multivariate analysis selected 3 factors associated significantly with an increased rate of acute restenosis: (1) dissection, (2) small balloon/artery diameter ratio and (3) low systolic blood pressure during PTCA. Reocclusion, which was defined as a total reobstruction of the lesion during hospitalization following emergency PTCA, was examined by predischarge coronary angiography. Acute restenosis correlated significantly with an increase in reocclusion rate. The incidence of documented reocclusion was 12%. Residual stenosis, multivessel disease and irregular dilation correlated significantly with an increased rate of reocclusion. The in-hospital and postdischarge mortalities were 5.6% and 2.1%, respectively. In summary, emergency PTCA produced a high angiographic success rate. Use of adequate balloon size and sufficient dilation correlated significantly with angiographic outcome in emergency PTCA. Patients with acute restenosis, high residual stenosis, irregular dilation, and multivessel disease would have a relatively high risk of reocclusion. PMID- 1404845 TI - Collagen in dilated cardiomyopathy--scanning electron microscopic and immunohistochemical observations. AB - The ultrastructural characteristics of collagen and the localization of collagen types were studied in formalin-fixed autopsied human hearts from patients who died in an advanced stage of dilated cardiomyopathy (DCM). The three-dimensional architecture of collagen fibers was studied by scanning electron microscopy by using the cell-maceration method. The localization of collagen type I-VI was demonstrated immunohistochemically using monoclonal antibodies specific to each collagen following the treatment of specimens with trypsin. In the hearts obtained from control subjects without heart disease, there were no significant differences in the ultrastructure and localization of collagens between the fresh and the formalin-fixed hearts. Therefore, formalin-fixation did not affect the ultrastructure of collagen or the immunoreactivity. In DCM, a dense endomysial weave network consisting of fine fibrils was associated predominantly with collagen type I and III, associated moderately with type VI collagen, but less associated with type IV collagen. Perimysial collagen bundles and collagen strands increased both in number and thickness. The outstanding finding was the presence of giant coiled perimysial fibers measuring about 20-30 microns in diameter. The prominent increase in perimysial fibrosis was closely associated with the accumulation of both type I and type III collagen, and associated moderately with type VI collagen. Interestingly, type V collagen increased in the intracellular matrix of the myocardium in DCM. Type II collagen was not present in either normal or diseased hearts. These structural and immunohistochemical characteristics of collagen may provide insights important to assessing the pathogenesis of the cardiac lesion of DCM. PMID- 1404844 TI - Precordial ST segment elevation in acute ischemia caused by right coronary artery occlusion. AB - The purpose of this study is to determine why precordial ST elevation (V1 lead) occurs during acute occlusion of the right coronary artery (RCA). Nineteen patients with vasospastic angina, in whom ergonovine administration into RCA provoked spasms, were divided into 2 groups by precordial ST change during spasms. Group I (n = 6) had precordial ST elevation; group II (n = 13) had no precordial ST elevation. A subgroup, IIA was comprised 6 patients in group II with spasms in the RCA proximal segment (segment number less than 2 of AHA coronary classification). None had left coronary dominancy. There was no difference in collateral flow during spasms. Location of spasms in group I was in the RCA proximal segment, and was significantly more proximal compared to group II. There was no difference in sigma ST in II, III, aVF between group I and II or IIA. Max ST elevation time by which duration of ischemia was estimated was significantly longer in group I than in group IIA. Three patients in group I displayed precordial ST depression before elevation, in all of whom in sigma ST in II, III, aVF was higher during precordial ST elevation than during depression. During acute occlusion in the RCA proximal segment, precordial ST elevation is caused by ischemia of the right ventricular anterior wall. Furthermore, precordial ST elevation can occur in a patient with RCA dominance, even if ischemic injury in the left ventricular infero-posterior wall increases progressively. PMID- 1404846 TI - Impairment of sarcolemmal permeability in the acute ischemic myocardium--a study with ionic lanthanum probe method. AB - Impairment of sarcolemmal permeability after the initiation of acute ischemic myocardial injury was studied using an ionic lanthanum (La3+) probe in electron microscopy. Acute ischemic myocardium was induced by ligation of the left anterior descending coronary artery in dogs. In normal cardiac myocytes La is localized exclusively in the extracellular space. i.e. on the glycocalyx, in the T-system and in intercalated discs, with normal fine structures. In ischemic myocardial cells, La deposits were found in the cytosolic space in 22% of subendocardial cells with mild to moderate, but non-necrotic, fine structural changes as early as 30 min. The number of myocytes with La deposition increased with advancing ischemic injury, and necrotic fine structural changes were recognized following ischemia for 60 min. These results indicate that deposition of La occurs before the appearance of irreversible morphologic alterations in ischemic myocardial cells, and suggest an increased permeability of the sarcolemma for Ca2+ and the development of degradation of plasma membrane integrity. PMID- 1404847 TI - Residual critical coronary stenosis during myocardial reperfusion is deleterious to myocardial salvage in dogs. AB - Hyperemia, which occurs immediately after coronary reperfusion, injures the myocardium. Mild coronary stenosis may mitigate this hyperemia and thus may augment myocardial salvage. To test this hypothesis, left anterior descending coronary arteries of dogs were occluded for 3 h. Then, reperfusion was permitted without residual stenosis (group A, n = 17) or with 75% stenosis (group B, n = 10). Regional myocardial blood flow (RMBF) was determined using colored microspheres. Dogs were sacrificed 1 week later to measure myocardial creatine kinase activity (CK) and for staining with triphenyl tetrazolium chloride (TTC). The RMBF measured 5 min after reperfusion increased significantly (inner layer, 171 +/- 16; outer layer, 165 +/- 11% of control) in group A. This hyperemia disappeared in group B (inner, 106 +/- 8; outer, 117 +/- 10% of control). However, the myocardial CK was more preserved (group A: inner, 31 +/- 4; outer, 44 +/- 4%; and group B: inner, 21 +/- 6; outer, 29 +/- 5%), and the infarct size was smaller in group A than in group B (group A: inner, 44 +/- 6; outer, 33 +/- 5; and group B: inner, 53 +/- 10; outer, 58 +/- 7% of the area at risk). We concluded that a residual stenosis of 75% at reperfusion abolishes the hyperemia but does not improve myocardial salvage. PMID- 1404849 TI - Spontaneous coronary artery dissection after a natural course for 10 years--a case report. AB - We encountered a patient with spontaneous coronary artery dissection complicated by acute inferior myocardial infarction. A 58-year-old male was admitted to our hospital due to acute inferior myocardial infarction in 1979. Coronary angiography performed 4 weeks after the onset showed a double lumen divided by a linear intimal flap in the right coronary artery, suggesting coronary artery dissection, but no apparent occlusion. Subsequently, he had been medicated with nitrates without any recurrent infarction. In February, 1989, 10 years after the first examination, coronary angiography was again performed and showed that the dissection had remained unchanged. Acetylcholine infusion into the right coronary artery induced coronary spasm. The prognosis of this condition seems to be better than has been generally considered, particularly in patients such as ours in whom the involvement of coronary spasm in the development of coronary artery dissection and myocardial infarction is suggested. When coronary spasm in controlled by treatment with nitrates or calcium antagonists, an uneventful course may be expected. PMID- 1404848 TI - Role of sympathetic nerve inhibition in the vasodepressor effect of bromocriptine in normotensive and hypertensive rats. AB - This study aimed to elucidate the mechanism of the hypotensive effect of bromocriptine (BRC), and to investigate whether or not the effects of BRC on the sympathetic nervous system are altered in hypertension. BRC was administered intravenously to normotensive and spontaneously hypertensive rats (SHR). It elicited hypotensive effects dose-dependently in urethane-anaesthetized normotensive rats, an effect which was antagonized with metoclopramide. Pretreatment with intravenous hexamethonium attenuated the hypotensive effect of BRC. BRC decreased plasma norepinephrine (NE) without inhibiting the sympathetic nerve spikes recorded from the postganglionic sympathetic nerve bundle. The hypotensive effect of BRC was significantly greater in SHR than in Wistar Kyoto Rats (WKY). Decrease in NE by BRC was also significantly greater in SHR than in WKY. These results suggest that the hypotensive effect of BRC is induced by suppression of NE release, not by inhibition of sympathetic nerve spikes, and that the dopaminergic presynaptic inhibition is attenuated in SHR. PMID- 1404850 TI - A right atrial thrombus, attached to the inferior limb of the fossa ovalis. AB - A right thrombus was incidentally found in a 65-year-old male during mitral valve surgery. A mushroom-like thrombus was attached to the inferior limb of the fossa ovalis with broad based stalk. It developed in sinus rhythm and in the absence of evidence of blood stasis in the right atrium. The most likely pathogenesis of right atrial thrombus formation in this case is endocardial damage from right heart catheterization prior to surgery. PMID- 1404851 TI - Pseudoaneurysm of the distal aortic arch in Behcet's disease--a case report. AB - Behcet's disease, manifested as a triform of relapsing iritis, stomatitis and genital ulceration, is now recognized as a systemic vasculitis that affects both veins and arteries. However, aneurysms of the aortic arch associated with Behcet's disease are extremely rare. We report on a successfully resected pseudoaneurysm of the distal aortic arch in a patient with Behcet's disease. The aneurysm was evaluated preoperatively by computed tomography (CT), magnetic resonance imaging (MRI) and intravenous digital subtraction angiography (DSA). We found that these non-invasive methods were quite useful for diagnosing the aneurysm in the aortic arch. Aneurysms enlarge rapidly when coupled with infection and are prone to rupture, thus requiring extensive surgical repair. However, since false aneurysm formations often occur at the site of anastomosis, postoperative follow-up should be monitored very closely. PMID- 1404852 TI - Fragmentation hemolysis in a patient with hypertrophic obstructive cardiomyopathy and mitral valve prolapse. AB - We encountered a 65-year-old female with hypertrophic obstructive cardiomyopathy and mitral valve prolapse who had infective endocarditis and hemolytic anemia. The infecting organism of endocarditis was group A streptococci. With regard to the etiology of the hemolytic anemia, fragmentation hemolysis was considered because fragmented red cells and elevated lactic dehydrogenase were observed. Haptoglobin was markedly decreased. Coombs' test, Ham's test and abnormal hemoglobin were negative. She had not had a hemolytic attack in the past. Ultrasonic cardiography showed asymmetrical septal hypertrophy, mitral valve prolapse and 285 mmHg of calculated pressure gradient in the left ventricle. Cardiac catheterization showed 115 mmHg of left intraventricular pressure gradient and mitral regurgitation (grade 2). Hemolysis was slightly improved after treatment with propranolol. Thus, fragmentation of the normal red cells seemed to be due to shear stress. PMID- 1404854 TI - [The 39th general meeting of The Japanese Association of Anesthesiology. Fukuoka, Japan, April 9-11, 1992. Abstracts]. PMID- 1404853 TI - [56th annual scientific meeting of the Japanese Circulation Society. March 25-27, 1992. Abstracts]. PMID- 1404855 TI - [The prognosis of patients with multiple myeloma--the aspect of histological distribution to the renal tissue and serum level of beta 2-MG]. AB - Beta-2-microglobulin (beta 2-MG) is a well-known tumor marker, particularly in patients with multiple myeloma (MM) in whom survival decrease in relation to high serum beta 2-MG concentrations. We investigated the level of serum beta 2-MG by radioimmunoassay (RIA) double antibody method in 14 cases of MM, 13 cases of benign monoclonal gammopathy, and 25 healthy controls. Beta-2-MG of the kidneys was stained by the MM by peroxidase-anti-peroxidase (PAP) method and clinical courses were compared. In controls, the serum beta 2-MG concentration increased with aging, and its concentration of MM was higher than that of controls. Most MM patients with positive beta 2-MG staining in glomeruli showed poor prognosis. Beta-2-MG staining of proximal and distal tubuli did not contribute to the prognosis of MM. PMID- 1404856 TI - [Clinical analysis of 10 patients with chronic lymphoid leukemia]. AB - Ten patients with chronic lymphoid leukemia were analyzed for clinical characteristics, morphology and phenotype of leukemic cells. There were 3 patients with T-chronic lymphocytic leukemia (CLL), 2 with T-prolymphocytic leukemia (PLL), 2 with B-CLL, 1 with B-PLL, 1 with non-T-non-B-CLL and 1 with Waldenstrom's macroglobulinemia. Although chronic lymphoid leukemia is usually characterized by proliferation of B-lymphocytes, our study revealed that 5 of 10 patients had T-cell phenotype. A peripheral blood specimen of T-CLL showed small lymphocytes with a mature appearance and an irregular nuclear margin. Most of the cells lacked large azurophilic granules in the cytoplasm and nucleoli were also inconspicuous in the nucleus by light and electron microscopic examinations. In PLL, a majority of the cells were large lymphocytes with a prominent nucleolus and abundant basophilic cytoplasm which were more clearly observed by transmitted electron microscopic examination. The patients were treated with cyclophosphamide and prednisolone, but response to treatment was transient. The median survival time was 7 months for all patients, while that of T-cell lineage cases was only 1 month. Therefore, new modalities of treatment must be investigated in the future. PMID- 1404857 TI - [Acute lymphoblastic leukemia with extensive demyelinated lesion of the brain stem during complete remission]. AB - A case of acute lymphoblastic leukemia (ALL) which showed extensive demyelinated lesion of the brain stem during complete remission is presented. A 13 year-old girl who was diagnosed as ALL in February, 1987 was treated according to the TCCSG L84-11 protocol, which induced complete remission in June, 1987. Her condition had been stable until April, 1988 when she abruptly complained of gait disturbance, vertigo and anorexia. She was subsequently admitted to our hospital. At the time of admission, she had ataxic gait, horizontal nystagmus towards right at dextroversion, bilateral exaggerated patellar tendon reflex, emotional incontinence, urinary incontinence and left 6th and 7th nerve palsy. In the middle of May, right spastic hemipalesia and hypesthesia became apparent. Left caudal pontine-basal lesion was suspected and was confirmed by MRI. Her synptoms progressed. Five months after admission, suffered repeated central apnea and died. Autopsy disclosed extensive cervical spinal cord. Cerebrum and cerebellum were intact. No evident findings suggesting the etiology were obtained. Whole skull radiation, intrathecal methotrexate, cytosine arabinoside and hydrocortisone might have contributed to the development of the demyelinated lesion. PMID- 1404858 TI - [Overt leukemia from MDS associated with marked basophilia]. AB - A 52-year-old woman was admitted to our hospital because of leukocytosis. She had been diagnosed with RAEB in another hospital in past time. At the admission, the white cell count was 30,900/microliter with blasts (14.0%) and marked basophilia (49.0%). Bone marrow aspiration revealed with 30.2% blasts and 21.1% basophils. Having obtained those results, diagnosis of RAEB in transformation was made. After admission, number of basophils in peripheral blood increased gradually, and level of histamine in serum was elevated significantly. Multiple peptic ulcers in stomach and bowel and high fever were induced due to histaminemia. Despite several therapy she died because of respiratory failure and septisemia. Although the mechanism of basophilia in this patient could not be clarified, there was a possibility that basophilia in this patient might be differentiated from leukemic clone because almost basophils in peripheral blood were mature and those had many granules including metachromasia by stained with toluidine blue. PMID- 1404859 TI - [Phenacetin-induced hemolytic anemia misdiagnosed as unstable hemoglobinopathy]. AB - A 30-year-old woman was admitted in August 1984 with anemia. She had an initial hemolytic attack in 1977. Unstable hemoglobinopathy was suspected. Despite splenectomy in 1979, hemolytic attacks continued. On admission, she was anemic and cyanotic. Hb heat denaturation test was positive. However, the first structure of amino acid of hemoglobin was normal. A large amount of white powder was found in her belongings, and was later identified as phenacetin. N-acetyl-P aminophenol, a metabolite of phenacetin was demonstrated in her urine. Hemolytic attacks disappeared completely after she stopped taking phenacetin. PMID- 1404860 TI - [Malignant lymphoma developing from the wall of chronic empyema following artificial pneumothorax]. AB - A 60-year-old man who had had chronic empyema following an artificial pneumothorax for pulmonary tuberculosis when he was 26 years old developed malignant lymphoma of the chest wall. The patient was admitted because of right pyothorax as a result of pseudomonas aeruginosa infection and underwent right thoracotomy. During lavage of the right thoracic cavity a tumor was found arising from the empyematic wall. Pathologic examination revealed that it was malignant lymphoma (diffuse large, immunoblastic, B cell type). Treatment with VEAP Bleomycin elicited a good response. Seven months after chemotherapy, the patient underwent thoracoplasty in addition to packing the cavity with the latissimus dorsi and the greater omentum. Following this, the patient received chemotherapy once a month for one and a half years, after which he was kept under close observation without treatment. Complete remission has now lasted for 49 months since the initial treatment. This is the first reported lymphoma case with closure of the empyematic wall and is remarkable since this patient has remained in complete remission for the last two years without any treatment. PMID- 1404861 TI - [Multiple hepatosplenic abscesses: successful treatment by continuous intraportal administration of amphotericin B in a case with acute promyelocytic leukemia]. AB - A 40-year-old female was admitted in August 1989 with a diagnosis of acute promyelocytic leukemia (AML; M3). One course of modified-DCMP regimen induced complete remission in September, but she developed spiking fever at a nadir period of WBC after induction chemotherapy. CT revealed multiple hepato-splenic abscesses presumably due to candida infection. She was treated with intravenous administration of amphotericin B (AMPH-B) and other antifungal agents. Despite the hematological remission and prolonged use of these antifungal agents, high fever persisted. A catheter was inserted into the portal vein under ultrasonic guidance. AMPH-B was administered through the catheter: the initial dose was 3 mg/day and was soon increased to 20 mg/day. Her fever subsided in 1 week, and the sizes of liver abscesses on CT reduced markedly. Chill and hypokalemia were observed during this therapy. The catheter was removed from the portal vein after 29 days. Partial portal vein thrombosis was noted around the catheter tip. This case suggests the usefulness of intraportal administration of AMPH-B in patients with hematological malignancy developing multiple liver abscesses. PMID- 1404862 TI - [Studies on pseudo-Chediak-Higashi granules formation in acute promyelocytic leukemia]. AB - Leukemic cells from acute promyelocytic leukemia containing pseudo-Chediak Higashi (P-CH) granules in a 38-year-woman were studied with ultrastructural and cytochemical techniques to evaluate the origin and nature of the granules. Wright Giemsa stain revealed giant granules to be azurophilic. Cytochemical stain revealed p-CH granules ot the basic of their peroxidase and glycoprotein content. Electron microscopy revealed numerous giant granules formed by fusion of azurophilic granules these morphological, different type granules were classified into four types, 1) circular granule with homogeneous matrix, 2) circular granule with heterogeneous change by autolysis, 3) Auer body-like granule with crystalline arrangement, 4) vacuolar formation. The results demonstrate that the Auer body-like granule of P-CH granules in leukemic cells is a morphologically variant type of the classical Auer body observed in common acute myeloid leukemia. PMID- 1404863 TI - [Non-Hodgkin's lymphoma in a patient with sarcoidosis (the sarcoidosis-lymphoma syndrome)]. AB - A-31-year-old man with right cervical and supraclavicular lymphadenopathy was admitted in March, 1991. He was diagnosed as having muscular sarcoidosis at the age 8 year, and was treated with corticosteroids. Since age 18, his skin was erythematous and ulcerous, and later his skin became gradually atrophic. Lymph node biopsy revealed diffused large cell non-Hodgkin's lymphoma. Lymphoma cells showed TCR-beta gene rearrangement by Southern blot hybridization. His lymphoma was refractory to CHOP and CHOP-Bleo regimens. Complete remission was achieved with cisplatin and etoposide. However, early relapse occurred, and he died of pulmonary hemorrhage 4 months after the diagnosis of non-Hodgkin's T-cell lymphoma. The so called "sarcoidosis-lymphoma syndrome" is uncommon in Japan. In 9 of 10 cases previously reported, malignant lymphoma occurred during the course of sarcoidosis. Most of the sarcoidosis cases were chronic active type, and required systemic administration of corticosteroids. Hodgkin's disease coexistent with sarcoidosis as reported in other countries, was not found in Japan. These findings suggest that the low incidence of sarcoidosis-lymphoma syndrome in our country is due to the relative rareness of Hodgkin's disease. The sarcoidosis lymphoma syndrome possibly appears as a consequence of immunological abnormalities observed in sarcoidosis. PMID- 1404864 TI - [Evolution to megakaryoblastic leukemia observed in myelodysplastic syndrome with erythrolekemia-like features]. AB - A 63-year-old man was admitted because of anemia and thrombocytopenia. The bone marrow was hypercellular with 66.6% erythroblasts with dysplasia and 19.8% blasts. Cytogenetically, MAKA (major karyotypic aberrations) containing 5q-, -7, 17, with karyotypic instability was observed. A diagnosis of erythroleukemia (FAB M6) was made. Six months later, immature neutrophils increased in the peripheral blood, and blasts and promyelocytes increased to 25.8% and 20.0% of marrow cells, respectively. Three months later, blasts asts increased to 33.0% in the peripheral blood. They were ultrastructually positive for platelet peroxidase. Phenotypically, 69% and 63% of blasts were positive for CD41b (GPIIb/IIIa) and CD42a (GPIb), respectively. Bone marrow biopsy showed marked proliferation of blasts and dysplastic megakaryocytes accompanied by reticulin fibrosis. These findings suggested evolution to megakaryoblastic leukemia (FAB M7). In most cases, M6 defined by the FAB criteria is stem cell disorder with multilineage involvement and major erythroid component. M6-like features may be observed in the evolutive phase to acute leukemia from myelodysplastic syndrome (MDS). PMID- 1404865 TI - [Thrombotic thrombocytopenic purpura achieving complete remission by slow infusion of vincristine]. AB - A case of thrombotic thrombocytopenic purpura (TTP) which was successfully treated by slow infusion of vincristine (VCR) is reported. A 40-year-old female was admitted to our hospital because of sudden onset of genital bleeding. Her blood cell count showed severe anemia and thrombocytopenia. Biochemistry disclosed high titers of serum LDH. Based upon these findings, the patient was initially diagnosed as having Evans syndrome and was treated with steroid-pulse therapy and high-dose immunoglobulin. However, no response was obtained. A diagnosis of TTP was established when mental disturbance and renal dysfunction developed later. Aspirin and plasmapheresis relieved the mental disturbance and decreased serum LDH level, but anemia and thrombocytopenia were not corrected. Slow infusion therapy of 1 to 2 mg VCR was performed for 4 to 8 hours once a week, which dramatically improved the hematological abnormalities and controlled the disease. In conclusion, slow infusion of VCR may indicated, if initial standard therapies such as PE would fail. PMID- 1404866 TI - [A case of hemophagocytic syndrome with multiple myeloma]. AB - A case with multiple myeloma complicated with hemophagocytic syndrome (HS) is presented. Because pancytopenia, liver dysfunction and increase of mature histiocytes in the bone marrow appeared rapidly a diagnosis of HS was made. The patient died of multiple organ failure, despite steroid therapy. Autopsy revealed marked invasion of hemophagocytic histiocytes not only into the bone marrow but also into many other organs such as the liver, lymph nodes and kidneys. HS is a histiocyte proliferative disorders, which is likely to be seen in immunocompromised hosts, but there is no previous report about HS and multiple myeloma. PMID- 1404867 TI - [Chimerism monitoring by VNTRs polymorphism analysis in a patient who received allogenic bone marrow transplantation]. AB - A 39-year-old female diagnosed as acute myelogenous leukemia received allogenic bone marrow transplantation (BMT) pre-conditioned with busulfan and cyclophosphamide regimen from her HLA identical sibling. To distinguish donor and recipient cells, we analyzed variable numbers of tandem repeats (VNTRs) polymorphisms using a YNH-24 probe by Southern blot hybridization. VNTRs polymorphism analysis documented the engraftment of donor cells, relapse of recipient cells, and mixed hematopoietic chimerism. Assessment of the chimerism state is important for determining the prognosis of patients undergoing BMT, and VNTRs polymorphisms analysis is very useful for identifying the chimerism state. PMID- 1404868 TI - [Cytokines involved in plasma cell proliferative disorders]. PMID- 1404869 TI - [Amino acid research--premises, frontiers, and prospects]. PMID- 1404870 TI - [Tracer kinetics of amino acid]. AB - In vivo turnover of an amino acid can be determined either by analysing the disappearance curve of a labeled amino acid after a single dose of labeled amino acid or by measuring the dilution of a continuously infused labeled amino acid at a steady state. From ethical concerns stable isotopically labeled amino acids, such as 13C-leucine and 15N-glycine have been routinely used to study amino acid kinetics with subsequent estimation of whole body protein turnover. Recently, instead of these 2 methods, pulse labeling by taking a single oral dose of labeled amino acid is more practical for the study of whole body protein turnover. We observed plasma 15N-glycine kinetics and urinary 15N excretion by a single oral dose of 15N-glycine simultaneously in healthy subjects and cirrhosis patients, and the results are discussed. PMID- 1404871 TI - [Phenylalanine transport in the living human brain by a dynamic PET of L-[2-18F] fluorophenylalanine]. AB - The transport kinetics of L-[2-18F]-Fluorophenylalanine in the human brain were studied in one normal subject and 6 patients with brain tumor using a dynamic positron emission tomography. The tracer kinetics from blood to brain were described by two compartment model with K1 (influx) and k2 (efflux). The rate constants in normal brain tissue and tumor tissue were K1 = 0.045 ml/g/min, k2 = 0.078 ml/g/min and K1 = 0.122 ml/g/min, k2 = 0.102 ml/g/min, respectively. The Michaelis-Menten constants (Kt and Tmax) for phenylalanine transport in the normal cortex were graphically estimated. The estimated Kt was 35 nmol/ml, whereas the Tmax varied with cerebral blood flow. PMID- 1404872 TI - [Membrane transport system of amino acids in the small intestine]. AB - The membrane transport system of amino acids in the small intestine is reviewed. Amino acids are transported by three processes: 1) simple diffusion, 2) facilitated diffusion and 3) active transport. In the brush border membrane, there are at least six Na(+)-dependent systems (NBB, PHE, IMINO, beta, X-G,A, Y+) and the Na(+)-independent systems (L, beta, Y+). On the other hand, the basolateral membrane has at least four Na(+)-dependent systems (A, ASC, X-G,A, N) and three Na(+)-independent systems (asc, L, y+). These systems are discussed. PMID- 1404873 TI - [Mode of membrane transport of amino acids--the kidney]. AB - In the kidney, more than 99% of filtered free amino acids are reabsorbed by the proximal tubule. The brush border membrane of this segment is known to possess at least 5 independent amino acid carriers; neutral alpha-amino, basic, acidic, neutral beta-amino and imino acid carriers. Ionic interactions have been shown to be markedly different among these carriers. Characteristics of the interaction were outlined for each carrier. Basolateral membrane carriers have not been investigated extensively, but existence of neutral amino acid carrier (s) devoid of ionic interaction has been established. In addition, a Na+ plus K+ gradient dependent transport has been identified for acidic amino acids and a Na+ exchange carrier has been suggested for basic amino acids. Also, asymmetric ionic interactions are suggested for luminal and basolateral membrane carriers for beta amino acids. Proton-dependent carrier (s) for di- and tri-peptides has also been identified in the proximal tubule. PMID- 1404874 TI - [Mechanism of amino acid transport at the liver plasma membrane]. AB - Several amino acid transport systems have been known in the liver: sodium dependent systems A, ASC and N for neutral amino acids, a sodium-dependent system for glycine (system Gly), sodium independent systems L1 and L2 for neutral amino acids, and sodium dependent systems for anionic amino acids. Recent studies with isolated sinusoidal and canalicular membrane vesicles have revealed that sodium dependent transport of an anionic amino acid, glutamate, and glycine occurs at the canalicular membrane, not at the sinusoidal membrane. Furthermore, solubilization and reconstitution of systems A and N has been reported and a 100 kD protein responsible for system N transport has been identified in the rat liver. PMID- 1404875 TI - [Molecular biological approach to mammalian amino acid transporters]. AB - Several mammalian amino acid transporters have been purified from solubilized membranes to a single protein band with a molecular mass of 60-130 kDa. It has been demonstrated that the mammalian amino acid transporters are expressed in Xenopus oocytes following microinjection of mRNA from various cells and tissues. Using this expression system, a cDNA clone, encoding an amino acid transporter, has been isolated from a tissue cDNA library, and a topological model for the deduced protein is depicted. At present, the models for the structure of the three kinds of amino acid transporters are proposed, one of which is identical with an ecopropic retrovirus receptor. PMID- 1404876 TI - [Molecular biological aspects of amino acid metabolizing enzymes]. AB - This article briefly describes the molecular biological aspect of studies on some enzymes involved in amino acid metabolism. Aspartate aminotransferase is one most extensively studied enzyme. Together with its three dimensional structure, recent studies using site-directed mutagenesis have led to the understanding of its structure-function relationships. Successful cDNA cloning of other aminotransferase has enabled us to understand the degree of homology in amino acid sequence. cDNAs for several amino acid decarboxylases were also cloned. Genomic structures for the enzymes involved in urea cycle have been studied. These studies have provided a molecular basis for some hyperammonemias. Its is strongly anticipated that the understanding of other metabolic disorders may be promoted by further accumulation of molecular biological data on the relevant enzymes. PMID- 1404877 TI - [Amino acids as a modulator of hormone secretion]. AB - Amino acids stimulate or inhibit the releases of some pituitary, pancreatic and gastrointestinal hormones by oral or intravenous administration. These effects are clinically used as amino acid loading tests to examine the reserve of hormones, including growth hormone, insulin, glucagon, somatostatin, etc., and of use for the diagnosis of endocrine and gastrointestinal diseases. The mechanism of pituitary hormone release, induced by amino acids, has been explained by their actions on peptidergic and monoaminergic systems in the brain but it is still not known as for pancreatic and gastrointestinal hormones. PMID- 1404878 TI - [Advances in automated amino acid analysis]. AB - Recent progress in the field of amino-acid analysis, characterized by the development of fully automated chromatographic equipment, is described. For separation and quantitation of free amino acids from biological fluid, such as blood and urine, ion exchange column chromatography followed by colorimetric detection of ninhydrin reactive products is the most widely adopted methodology in the clinical field. Analytic procedures are fully automated. The computer controlled pumping mechanism guarantees a precise buffer supply for separation and peak identification and peak height or/and area detection of each amino acid in the effluent are highly reproducible. Complete analysis of more than 30 amino acids in biological fluids can be performed within 2 hours. Amino acid analysis is now easily adopted in the routine clinical laboratory and is expected to contribute to the clinical diagnosis of amino acidopathies. PMID- 1404879 TI - [Inborn errors of amino acid metabolism--concepts and classification]. AB - After the definition and the heredity of inborn errors of amino acid metabolism and a discussion of the incidence of these diseases, the four primary types of clinical features, namely 1) the prenatal, 2) neonatal (with acute onset), 3) mild, and 4) abortive types are described. The pathophysiology of brain damage is discussed. Based on recent findings, inborn errors of amino acid metabolism were classified according to their cause, 1) primary defect in catabolism, and 2) disturbances in the transport of amino acid. For each disease, the amino acids which can be detected in the plasma or in the urine are listed, along with the enzymes which are defective in each case. PMID- 1404880 TI - [Biochemical diagnosis and mass screening for hereditary amino acid disorders]. AB - During the past 50 years, the development of both organic and analytical chemistry has greatly contributed to the discovery of new hereditary amino acid disorders. As a result, more than 80 new amino acid disorders have been discovered. More recently, the development of protein chemistry has made it easily to investigate the biochemical basis of these disorders. In this paper we present the status of biochemical diagnosis as well as mass-screening for amino acid disorders. The result of neonatal mass-screening for 4 amino acid disorders (PKU, MSUD, homocystinuria and histidinemia) from 1977 to 1990 revealed that the incidence of PKU is extremely rare in Japan when compared to European Countries, and the incidence of MSUD and homocystinuria are also less common in Japan. On the other hand, the incidence of histidinemia is higher in Japan than in Europe, however, a follow up study of more than 1,500 patients showed almost all cases developed normally without any dietary treatment. PMID- 1404882 TI - [Inherited metabolic disorders of the transsulfuration pathway]. AB - Several inherited metabolic disorders of the transsulfuration pathway are discussed. They are hypermethioninemia, homocystinuria, cystathioninuria, beta mercaptolactate cysteine disulfideuria and sulfite oxidase deficiency (SOD). Primary coverage is given to homocystinuria and SOD. In the case of homocystinuria, metabolic defects include cystathionine beta-synthase deficiency, methylenetetrahydroforate reductase deficiency, and mutations in cobalamin metabolism. Their main clinical pictures, metabolic abnormalities, and treatment are also described. SOD appears in two cases as an isolated enzyme defect and a combined deficiency of sulfite oxidase and xanthine dehydrogenase that share a common molybdenum cofactor. The clinical, biochemical and neurological features of the two disorders are reviewed. PMID- 1404881 TI - [Prenatal diagnosis of inborn error of amino acid metabolism]. AB - Prenatal diagnosis of inborn errors of amino acid metabolism was discussed from the viewpoints of its purpose, ethical problems, analysis methods, and sampling methods of the fetal tissues. In addition to the general discussion, our results of the prenatal diagnosis of 20 cases with nonketotic hyperglycinemia (NKH) were also reported. Nineteen cases were diagnosed by the enzymatic method, while one Finnish case was successfully diagnosed by DNA analysis, which is based on our observation that a missense mutation we identified accounts for 70% of the mutant alleles in Finland. The DNA analysis would be a great help for the prenatal diagnosis in Finland where the incidence of NKH is unusually high (1: 12,000 births). PMID- 1404883 TI - [The dibasic amino acid metabolic disorders]. AB - The ornithine transcarbamylase deficiency (OTCD), arginase deficiency (ARD), Hyperornithinemia-Hyperammonemia-Homocitrullinuria (H.H.H) syndrome and Lysinuric protein intolerance (LPI) are characterized by the accumulation of the precursors of urea, principally ammonia because of the abnormal metabolism of ornithine, arginine and lysine which are the dibasic amino acid. We mainly described the recent knowledge for these disease and introduced the great advancement of the molecular biology in this field which makes us to give an early diagnosis for these disease to have an early treatment. PMID- 1404884 TI - [Metabolic disorders of amino acids due to enzyme mutation--branched-chain amino acids]. AB - Three kinds of inborn error of branched-chain amino acids (valine, leucine isoleucine) are described with a focus on the findings in recent biochemistry and molecular genetics. Frequency of valinemia and leucinisoleucinemia is quite low but their significance is distinct because of our knowledge that at least two aminotransferases, one branched-chain keto acids dehydrogenase and two short chain acyl-CoA dehydrogenases are present in human, is based on the observations of these limited cases. In MSUD, the sequential study of each subunit cDNA reveals a close relationship between the clinical phenotypes and the various sites of mutation. PMID- 1404885 TI - [Inborn errors of imino acid metabolism]. AB - Several conditions and disorders were caused by enzyme defects in metabolism of imino acids. Hyperprolinemia type I and type II, hyperhydroxyprolinemia, imidopeptiduria (prolidase deficiency) were related to proline and/or hydroxyproline metabolism. Sarcosinemia and abnormality in pipecolic acid metabolism were also classified as inborn errors of imino acid metabolism. In this brief review, the outline of these genetic conditions or disorders were described. Among the genetic enzyme defects, imidopeptiduria (prolidase deficiency) caused severe clinical problems. Other conditions were thought to be benign. PMID- 1404886 TI - [Abnormal metabolism of substances related to glycine and beta-alanine]. AB - Glycine and serine are interconverted by serine hydroxymethyltransferase and hence share their metabolic pathways. In the rat the carbon skeleton of choline is derived from the alpha and beta carbons of serine through phosphatidylserine and is further converted to that of glycine through N-methylated molecules of glycine i.e. betaine, N-dimethylglycine, and sarcosine (N-methylglycine). Thus far, the production of a folate derivative of the active one carbon that is an essential material for purine nucleotides and thymidylate biosynthesis is the notable feature of this metabolic process. In the major degradative pathway for pyrimidine nucleotides, beta-alanine, one of omega-amino acids, is produced and further catabolized by beta-alanine: oxoglutarate transaminase which is suggested to be identical to that for gamma-aminobutyrate, another omega-amino acid. Disorders included in these metabolic pathways are succinctly reviewed. PMID- 1404887 TI - [Vitamin B6 dependency syndrome]. AB - Many enzymes that require pyridoxal 5'-phosphate (PLP), a coenzyme from a vitamin B6, are involved in amino acid metabolism. B6 dependency syndromes are defined as a group of metabolic disorders which are prevented or alleviated by non physiologically large doses of vitamin B6, and, hence, they are tacitly accounted for by some structural alteration in a responsible B6-dependent enzyme such as a decrease on the affinity for PLP as compared to the normal. In this article, the mode of binding the coenzyme is exemplified by the case of aspartate aminotransferase, a typical B6-dependent enzyme whose three-dimensional structure is known, and, several B6 dependency syndromes are briefly reviewed. Among these syndromes, the molecular basis of only gyrate atrophy has recently been defined by the identification of a mutation in the relevant enzyme, ornithine aminotransferase. PMID- 1404888 TI - [Inherited amino acid transport disorders]. AB - Disorders due to inherited amino acids transport defect are reviewed. The disorders were categorized into three types of transport defects, namely, brush border membrane of epithelial cells of small intestine and kidney tubules (Hartnup disease, blue diaper syndrome, cystinuria, iminoglycinuria and lysine malabsorption syndrome), basolateral membrane (lysinuric protein intolerance) and membrane of intracellular organelles (cystinosis and hyperornitinemia hyperammonemia-homocitrullinuria syndrome). Pathogenesis, clinical feature, laboratory findings, diagnosis, genetics and treatment of these disorders are described, briefly. There is not much data for the transport systems themselves, so that further investigation in molecular and gene levels for transport systems is necessary to clarify the characteristics of the transport and heterogeneity of phenotypes in inherited amino acids transport disorders. PMID- 1404889 TI - [Cystinosis]. AB - Recent progress of the study of the pathogenesis, diagnosis, and treatment of a lysosomal transport disorder, cystinosis is reviewed. Cystinosis is an autosomal recessively inherited disease that is caused by the accumulation of cystine in lysosome due to lack of the cystine transport system in lysosome. Renal transplantation has been a successful treatment for the cystinosis patients who are in the end stage renal failure, and this therapy has markedly prolonged the life span of cystinosis patients. Recently, oral cysteamine therapy has been successful in the excretion of accumulated cystine in cystinosis patients, and in improving the symptoms. Studies are now under way to see if early (within a month of life) start of cysteamine therapy would achieve the most satisfactory therapeutic effect and maintain normal renal function. PMID- 1404890 TI - [Imbalance of amino acid metabolism in fulminant hepatitis and its management]. AB - Fulminant hepatitis shows characteristic imbalance of amino acid levels; increased aromatic amino acid (AAA) and methionine. Elevated plasma AAA may cause hepatic encephalopathy and BCAA-enriched amino acids solution (BCAAs). Glucagon Insulin (G-I) therapy and artificial liver support system have been proposed to correct the imbalance of amino acids. BCAAs and G-I therapy correct the aberrant amino acid patterns and artificial liver support system, including plasma pheresis, and charcoal haemoperfusion has also been used to reduce plasma amino acids levels. While imbalance of amino acids level in fulminant hepatitis is a result of acute necrosis of a large proportion of hepatocytes, careful and sufficient management of the disease is essential to normalize amino acid profiles. PMID- 1404891 TI - [Amino acid metabolism in liver cirrhosis]. AB - In patients with liver cirrhosis the fasting plasma alpha-amino nitrogen concentration is high as the rule, due to reduced clearance of total alpha-amino nitrogen. The urea cycle is diminished of its capacity in cirrhotic patients than in the control subject, and to compensate for this, the extrahepatic glutamine cycle capacity is enlarged in the patients. The following important topics were taken up in this mini review: some problems concerning Fischer ratio, amino acids metabolism and pH regulation in the liver, and the supplementation therapy with branched chain amino acids under the condition of organ relationship. PMID- 1404892 TI - [Amino acids metabolism and nutritional support in acute renal failure]. AB - It has been claimed that conventional essential amino acid (EAA) solution may give rise to adverse effects such as hyperammonemia, in acute renal failure (ARF). On the other hand the majority the ARF treated recently have been complicated by multiple organ failure (MOF). These data indicate that a new regimen in nutritional support should be applied to those patients. A new amino acid solution for renal failure, containing not only EAA but also branched chain and non-essential amino acids, has been developed. We administered this solution as total parenteral nutrition (TPN) to ARF patients complicated by MOF. Continuous hemodiafiltration is simultaneously applied to remove excess water. The nutritional status and the deranged aminogram are improved by this treatment. We believe that an ARF patient complicated by MOF should be nutritionally supported with this new regimen. PMID- 1404893 TI - [Impaired amino acid metabolism and its management in chronic renal failure]. AB - The protein and amino acids (AAs) metabolism are known to be impaired in the uremic patients. The etiology of those abnormalities is multifactorial, such as inadequate nutritional intake, protein-restricted diet, decreased urinary excretion of AAs, impaired activity of AAs-synthetic and/or-degrading enzymes, disturbed absorption, loss of AAs during dialysis, and abnormal transcellular movement due to hormonal abnormalities. As the nutritional supplement for the uremic patient, essential amino acid has been proposed. It was, however, reported to cause the hyperammonemia with or without encephalopathy in addition to fatty liver. Further investigation concerning the optimal composition of AAs solution for uremic patients is required to solve these problems. PMID- 1404894 TI - [Amino acid metabolism in surgical stress]. AB - Amino acid metabolism under surgical stress, injury or infection was reviewed from the literature. The glucose-alanine cycle in coupling with branched chain amino acids (BCAA) metabolism plays a central role for gluconeogenesis, in such a catabolic state. Glutamine is as important as alanine for sparing glucose and furthermore for intestinal repair. Changes in plasma amino acid concentration and clearance following hepatectomy are described, and effects of BCAA solution are evaluated. It was suggested that BCAA improved the Fischer ratio by increasing, not only plasma BCAA level, but also AAA clearance. PMID- 1404895 TI - [Abnormal amino acid metabolism in diabetes mellitus]. AB - Abnormal amino acid metabolism is sometimes observed among patients with diabetes mellitus. Of many amino acids, alanine and branched-chain amino acids such as valine, leucine, isoleucine show characteristic changes. In diabetic ketoacidosis, plasma concentration of alanine decreases and that of branched amino acid increases and the oxidation of branched-amino acids is enhanced. Splanchnic amino acid uptake is generally higher in diabetics and this level is partially restored by exercise. Some glycosylated proteins are used to estimate the condition of diabetes mellitus. Increment of urinary glycosylated amino acid excretion is reported in diabetics. Plasma homocysteine, reactive vascular injuring amino acid, increases in diabetics with nephropathy. Those abnormal amino acid metabolism would be restored after good glycemic control is obtained. PMID- 1404896 TI - [Eosinophilia-myalgia syndrome]. AB - Eosinophilia-myalgia syndrome (EMS) is a newly recognized disease, characterized by peripheral eosinophilia with scleroderma-like features. By July 1991, 1543 cases of EMS, including 31 fatal cases, have been reported. Although epidemiologic studies strongly suggest the association of EMS with ingestion of L tryptophan (LT) containing a contaminant from a single manufacture, the pathogenesis of this disease is not well understood. The insight obtained from the study of EMS may be applicable to scleroderma or eosinophilic fasciitis. Recent advances in the understanding of clinical and pathologic features of EMS are reviewed. PMID- 1404897 TI - [Immuno-hematopoietic cytokine receptor family--its structure and function]. AB - Receptors for immuno-hematopoietic cytokines are multi-chain complexes of membrane proteins. Molecular cloning of these cytokine receptor genes revealed the existence of a here-to-fore unidentified receptor superfamily. They are primarily characterized by a shared extracellular structure that may be involved in the formation of multi-chain receptor complex. Inspite of the lack of any catalytic function, several members of the superfamily are known to act as the transmembrane transducers of cytokine signals. Such molecules may interact physiologically/functionally with multiple intracellular catalytic molecules to generate signals. In this regard, potential involvement of protein tyrosine kinase and protein serine/threonine kinase in the post-receptor signalling has been described. Dysregulated activation of the cytokine receptor gives rise to transformation of immuno-hematopoietic cells. PMID- 1404898 TI - [Development and application of biosensors for medical field]. AB - Methods for the selective determination of organic compounds in biological fluids, such as blood, are very important in clinical analyses. Most analyses of organic compounds can be performed by spectrophotometric methods, based on specific enzyme-catalyzed reactions. However, because of the complicated procedure, these methods cannot be applied directly to bed-side monitoring. Alternatively, biosensors based on enzymes and electrochemical transducers possess excellent sensitivity for biological substrates and can determine a single compound in a biological fluid directly without need for a prior separation step. Therefore, in the past several years, many kinds of biosensors have been developed, and implantable microbiosensors for a body organ have also been reported. PMID- 1404899 TI - [A study of hepatocellular transplantation]. AB - Clinical liver transplantation has been done for patients with irreversible hepatic diseases, but the shortage of donor livers from heart beating cadavers has become very serious. Hepatocyte transplantation requires no vascular anastomosis and donor hepatocytes are easy to obtain from living donors and easy to preserve for a long time. In the animal experiments, transplanted hepatocytes survived in the spleen for long periods of time, and cytochemical investigation revealed differentiated liver functions, such as gluconeogenesis, albumin synthesis, bilirubin conjugation. Intrasplenic transplantation of hepatocytes relieved congenital disorders of liver enzymes in rats. Moreover, transplanted hepatocytes re-composed normal cord structures with hepatic sinusoids in the spleen of rats. Hepatocytes could also be isolated from human cirrhotic livers by a multi-perfusion method, and the viability was almost 80%. After the success in transplantation of human hepatocytes into the spleen of athymic mice, 6 patients have undergone clinical trial of intrasplenic hepatocyte transplantation without any complications. In the future, the progress of gene manipulation techniques may make possible rapid growth of transplanted hepatocytes. Intrasplenic transplantation of isolated hepatocytes provides an in-vivo experimental model to study cellular growth and functions in detail. PMID- 1404900 TI - [Introduction--gene diagnosis of infectious diseases]. PMID- 1404901 TI - [Application of PCR to molecular epidemiology]. PMID- 1404902 TI - [Pulsed-field gel electrophoresis for molecular epidemiology of nosocomial infections]. PMID- 1404903 TI - [Genetic diagnosis and molecular epidemiology of viral infections]. PMID- 1404904 TI - [Genome of adenovirus and the molecular epidemiology of adenoviral infections]. PMID- 1404905 TI - [Recent trend and progress in molecular diagnosis and epidemiology of (protozoan) parasitic diseases]. PMID- 1404906 TI - [Molecular diagnosis of human parvovirus B 19 infections]. PMID- 1404907 TI - [Nucleotide sequences of HBsAg in Japan]. PMID- 1404908 TI - [Analysis of mutations in precore and core regions of HBV genome by PCR]. PMID- 1404909 TI - [Detection of influenza virus using the polymerase chain reaction]. PMID- 1404910 TI - [Analysis of mumps virus genome and application of the PCR for identification of the mumps virus strains]. PMID- 1404911 TI - [Laboratory medicine and gene diagnosis in infectious diseases]. PMID- 1404912 TI - [Prenatal diagnosis of rubella by genome detection]. PMID- 1404913 TI - [DNA diagnosis of HIV-1 carriers by PCR]. PMID- 1404915 TI - [Rapid identification of mycobacteria by hybridization protection assay (HPA, ACCUPROBE)]. PMID- 1404914 TI - [Detection of HTLV-1 proviral DNA with nested PCR]. PMID- 1404916 TI - [The highly-sensitive method of detecting mycobacteria from sputa by using PCR]. PMID- 1404917 TI - [Toxin-typing by PCR of streptococcal pyrogenic exotoxin produced by Streptococcus pyogenes]. PMID- 1404918 TI - [Genetic diagnosis of MRSA infection by PCR method]. PMID- 1404919 TI - [Differentiation and detection of pathogenic determinants among diarrheogenic Escherichia coli by polymerase chain reaction using mixed primers]. PMID- 1404920 TI - [Methods to detect the thermostable direct hemolysin gene and a related hemolysin gene of Vibrio parahaemolyticus by PCR]. PMID- 1404921 TI - [Basic principles for genetic diagnosis of infectious diseases]. PMID- 1404922 TI - [DNA sequence for Campylobacter species and their detection and identification by PCR]. PMID- 1404923 TI - [Development and application of polymerase chain reaction (PCR) and DNA hybridization for detection of cholera enterotoxin-producing V. cholerae and other pathogens]. PMID- 1404924 TI - [Genetic analysis of Shigella pathogenesis and rapid detection method of Shigella virulence gene by the polymerase chain reaction]. PMID- 1404925 TI - [Detection of salmonellae by hybridization using nonradioisotopic DNA probes]. PMID- 1404926 TI - [Detection and identification method of pathogenic Yersinia by PCR technique]. PMID- 1404927 TI - [Rapid identification of nonfermentative gram-negative bacilli by photobiotin labeled deoxyribonucleic acid-deoxyribonucleic acid hybridization]. PMID- 1404928 TI - [Clinical specimen preparation for genetic diagnosis]. PMID- 1404929 TI - [Detection of Neisseria gonorrhoeae by a DNA probe test]. PMID- 1404930 TI - [Detection and identification of Legionella species by PCR]. PMID- 1404931 TI - [Development of a DNA probe specific for Bacteroides fragilis: use of the cloned neuraminidase gene]. PMID- 1404932 TI - [The rapid and sensitive detection of Listeria monocytogenes (the causative agent of listeriosis) by DNA amplification]. PMID- 1404933 TI - [Detection of Chlamydia trachomatis and the serovar determination using PCR and dot-blot hybridization]. PMID- 1404934 TI - [Detection of Rickettsia tsutsugamushi DNA by polymerase chain reaction]. PMID- 1404935 TI - [Rapid detection method for Mycoplasma pneumoniae by polymerase chain reaction]. PMID- 1404936 TI - [Sensitive and specific detection of Candida albicans by polymerase chain reaction]. PMID- 1404937 TI - [Detection of Pneumocystis carinii with DNA amplification]. PMID- 1404938 TI - [Distinguishing between pathogenic and nonpathogenic isolates of Entamoeba histolytica by polymerase chain reaction]. PMID- 1404940 TI - [Progress report on the DNA probe diagnosis of malaria]. PMID- 1404939 TI - [Application of PCR technique for rapid identification of acanthamoeba]. PMID- 1404941 TI - [The detection and characterization of drug resistant malaria parasites using genetic markers]. PMID- 1404942 TI - [Molecular biology of Leishmania and diagnosis of leishmaniasis by DNA probe]. PMID- 1404943 TI - [Diagnosis of trypanosomiasis with the parasite specific DNA probes--non radioactive probes and PCR methods]. PMID- 1404944 TI - [A DNA-probe list for the development of diagnosis of infectious diseases]. PMID- 1404945 TI - [Lysis protocol for bacteria]. PMID- 1404946 TI - [Hybridization technology for DNA diagnosis of infectious disease and examples in commercially available kits]. PMID- 1404947 TI - [Commercially available nucleic acid probes for infectious diseases]. PMID- 1404948 TI - [Aqueous phase hybridization]. PMID- 1404949 TI - [Microplate hybridization method]. PMID- 1404950 TI - [Diagnosis of viral infections with an automatic machine for in situ hybridization and immunohistochemistry]. PMID- 1404951 TI - [Genetic diagnosis and molecular epidemiology of bacterial infections]. PMID- 1404952 TI - [Application of PCR for DNA diagnosis in infectious diseases]. PMID- 1404954 TI - [Evaluation and selection of normal range calculation methods]. AB - There are many methods for normal range calculation, and they give different values even with the same normal data sample. I proposed three parameters, accuracy, precision and robustness, for evaluating the calculation methods. A complicated calculation method, the distribution selection method, seems to be theoretically correct, but it shows unstable precision and inadequate robustness when the normal data contain a small amount of abnormal data. A method called "Clinical reference range program (CRRP)" is a robust method, and is applicable to the data which contains abnormal data. I also proposed a condition which defines the sample size required for the calculation using the precision parameter. PMID- 1404953 TI - [Present status and problems of the normal values (clinical reference range) of the laboratory tests--results of a questionnaire survey in university hospitals in Japan]. AB - The normal values (clinical references range) of the laboratory tests differs among hospitals due to the differences in: (1) the kinds of instruments and reagents used, (2) how the population for study was selected and the size of the population was, (3) when the specimens were taken, (4) how they were stored until use, and (5) how the data obtained were calculated and (6) who evaluated the results. In this study, questionnaires regarding the above-mentioned points were sent to the heads of the clinical laboratories in 80 university hospitals in Japan. Answers were received from 71 laboratories (the rate of recovery was 88.8%). The normal range of potassium, uric acid, total cholesterol, enzyme activities [ALP, LDH, CHE, AST (GOT) and ALT (GPT)] in the university hospitals in Japan varied. It is not ideal to use different reference values in different hospitals. However, it is impossible to prepare a standard manual to obtain the normal range at present. When the inter-hospital differences become small enough to obtain one normal range for the Japanese peoples, a standard manual for normal values should be made. PMID- 1404955 TI - [Factors that influence reference values]. AB - The factors that influence reference values are briefly reviewed using our experimental data. The factors can be divided into the following 3 subfactors: analytical technology, selection of so called healthy person and statistical method. The most large effect came from a variety of physiological conditions in healthy persons, i.e., age, sex, diurnal and menstrual rhythms, drinking and smoking habits, diet, physical exercise, posture, tourniquet etc. A new concept of tow-step reference values "the basal value and the equivocal value" is postulated from the studies of the effect of these physiological conditions. The effects of the statistical methods for obtaining the distribution type of data of normal reference group and the 95% reference range were not so large. Then, we conclude that the reference values or the reference ranges should be made in your own laboratories using carefully selected healthy persons even if 30 or 50 small numbers are used. PMID- 1404956 TI - [Methods and normal ranges for predicting diseases]. AB - Predictions of diseases require suitable laboratory tests, mathematical methods for analyzing data and true normal ranges. Normal ranges are to be defined as 95% range of test results obtained on healthy subjects. "Healthy" subjects here refers to the persons who are free of the particular disease now and previously. However, to confirm the disease-free condition, laboratory test result must be evaluated on the basis of a normal range. This is a dilemma. The only way to overcome this problem is to follow a cohort for 10 or 20 years. Some of the "healthy" subjects will be suffering from diseases, while the others will still remain free of disease. That the latter persons would be the truly "healthy" subjects. Therefore, by their laboratory data and/or specimens such as serum every year we can determine the differences between the laboratory data of the patients and the true healthy subjects. In this respect, the development of laboratory database systems and serum banks are essential. We report a mathematical method for selecting significant data items for such a database and decision-making. PMID- 1404957 TI - [Detection of mRNA in megakaryocytes using in situ hybridization]. AB - The usefulness of in situ hybridization for detecting mRNA encoding various kinds of proteins in megakaryocytic cell lines (K562, HEL and CMK) was examined. Using in situ hybridization, glycoprotein (GP) IIIa mRNA was found to be present in K562, HEL and CMK cells. Both GPIb and GPIIb mRNA were also present in HEL and CMK cells, while only HEL cells expressed platelet factor 4 mRNA. These findings were identical to those obtained with Northern blotting. It should be emphasized that in situ hybridization was useful to clearly define each cell expressing platelet specific protein mRNA. The expression of interleukin-6 (IL-6) and IL-6 receptor mRNA in mononuclear cells prepared from bone marrow aspirates was examined. In situ hybridization study demonstrated the presence of IL-6 receptor mRNA in the recognized megakaryocytes only, while IL-6 mRNA was found to be present in the megakaryocytes and a few mononuclear cells. These findings suggest that differentiation and proliferation of normal megakaryocytes might be controlled by an IL-6 autocrine loop, and detection of IL-6 receptor mRNA might be useful to identify megakaryocytes. PMID- 1404958 TI - [Evaluation of clinical features, cytopathological findings and prognosis of histiocyte proliferative disorders]. AB - Clinicopathological analysis was performed in 19 patients diagnosed clinically with malignant histiocytosis. Ultimately, 9 patients died and 10 are still alive. All 19 had fever of unknown origin. Among the 10 surviving patients, 6 recovered with only supportive therapy such as antibiotic treatment. One recovered with steroid therapy and 2 with VP (vincristine and prednisolone) therapy. Complications due to immunodeficiency were detected in one surviving patient and 2 who died. All 9 patients who died had anemia, and 8 had thrombocytopenia. However, among survivors, only one had anemia and only 2 had thrombocytopenia. Chromosomal abnormality was detected in one patient who died. Histiocytic cells were classified morphologically into 3 types: immature, intermediate and mature. In 4 patients who died, histiocytic cells were immature, but in 4 others mature histiocytic cells were detected. In 5 of the 10 surviving patients, histiocytic cells were of the immature type. Immuno-histochemical analysis of the origin of histiocytic cells in 8 deceased patients showed T-zone histiocytes in one, T cells in one, monocyte phagocytic system (MPS) in 5, and histiocytes of unknown origin in one. Thus, malignant histiocytosis is a heterogenous entity including reactive histiocytic disorder, lymphocytic neoplasm and true histiocytic neoplasm. In histiocyte proliferative disorders, red blood cell counts and platelet counts are useful for assessing prognosis, while cytological findings only confuse this evaluation. PMID- 1404959 TI - [Evaluation of platelet aggregation test by grading curve]. AB - In order to standardize the platelet aggregation test, we used the grading curve (GC) produced by plotting four concentrations (0.5, 1.0, 2.0 and 4.0 microM) of ADP and four concentrations (0.25, 0.5, 1.0 and 2.0 micrograms/ml) of collagen, which are aggregation inducers, along the horizontal axis and plotting their individual rates (%) of aggregation 5 minutes after administration, along the longitudinal axis. The degree of platelet aggregation was classified in 6 stages (Types III, II, I, 0, -I and -II), ranging from marked increase to marked decrease, according to the GC of ADP aggregation in healthy subjects. Type I or 0 ADP aggregation was observed in 78% of the subjects, and Type I collagen aggregation was observed in about 50% of the subjects, whereas patients with cerebral infarction showed distinct increases in Type III and II aggregations of both ADP and collagen. In most patients who were treated with antiplatelet drugs, the aggregation were Type 0, -I or -II. The concentration of inducer, which corresponded to the maximum 50% value of the GC (Max 50) was significantly correlated with the minimum concentration (threshold concentration) in ADP aggregation, at which secondary aggregation was induced even if it was reversible, and with the minimum concentration (threshold concentration) in collagen aggregation, at which the aggregation rate 5 minutes after administration increased to 50% or higher. The GC of platelet aggregation seemed to enable easy determination of the degree of aggregation, and was also considered to be useful for monitoring platelet aggregation during the administration of antiplatelet drugs. PMID- 1404960 TI - [Negative interference with peroxidase-coupled enzymatic serum creatinine assay by a hemostatic drug containing a hydroquinone structure]. AB - We report a discrepancy between serum creatinine levels obtained by the method based on alkaline picric acid (Jaffe reaction) and that by automated analyzer employing enzymatic assay based on peroxidase-coupled reaction in a patient with renal dysfunction taking Ethamsylate, a capillary vessel stabilizer. Serum creatinine level obtained by the Jaffe reaction was 83 mg/l, and that by the enzymatic method was 22 mg/l. Recovery test of creatinine using the patient's serum showed 101 to 102% recovery by the Jaffe reaction and 77 to 89% by the enzymatic method. The same results were observed both in an in vitro test and in serum obtained from a healthy volunteer who had been given Ethamsylate previously. As the chemical structure of Ethamsylate includes a hydroquinone unit, it was thought that the compound may consume hydrogen peroxide produced by the reaction of peroxidase as the hydrogen donor and compete with the substrate used as the hydrogen donor for the color development. Thus evaluation of test results obtained by peroxidase coupled methods should be carefully interpreted in a patient who is consuming drugs which hydrogen peroxide such as hydroquinone. PMID- 1404961 TI - [Clinical assessment of urinary free L-fucose levels]. AB - We measured urinary levels of free L-fucose in healthy subjects, patients with benign diseases, and patients with cancer using an automated analyzer and a newly isolated L-fucose dehydrogenase, and evaluated the clinical usefulness of the results. The values obtained were corrected for urinary creatinine as micromoles per gram of creatinine. The cutoff value, set at the mean + 2SD for the healthy subjects, was 250 mumol/g.Cr. Patients with gallbladder cancer, bile-duct cancer, liver cancer, pancreatic cancer, or cirrhosis of the liver had significantly higher levels of L-fucose than the healthy subjects. The diagnostic sensitivity for these five diseases, taken together, was 68% (144/213). Specificity for the detection of cancer was calculated by use of false positives for patients with cholelithiasis, hepatitis, and pancreatitis: it was 73% (76/104). Diagnostic accuracy for these seven diseases taken together was therefore 69% (220/317). We compared the positive ratio of the L-fucose level with that of the tumor markers AFD and CA19-9. The positive ratio of an L-fucose value above the cutoff was higher than the positive ratio of either marker in bile-duct cancer, gallbladder cancer, liver cancer, and pancreatic cancer. The results suggested that the urinary levels of free L-fucose reflected the metabolism of sugar chains of glycoconjugates, and may be usefully clinically as a tumor marker. PMID- 1404962 TI - [Creatine kinase activity and its isozyme levels in cord blood]. AB - We measured creatine kinase (CK) levels of cord blood and evaluated them in relation to the degree of maturity and distress. The reference value of CK of cord blood in normal neonates was 209 +/- 99 U/l (mean +/- SD) and the percent values of the isoenzymes, CK-MM, CK-MB and CK-BB, were 86.7 +/- 6.2%, 5.1 +/- 2.6%, and 8.1 +/- 5.4%, respectively. There was a positive correlation between the birth weight and CK, CK-MM, CK-MB and CK-BB levels of cord blood. The CK and CK-MM levels of cord blood in the neonates who were prematurely delivered and small-for-date were significantly lower than those in normal controls. The CK and CK-MM levels of cord blood in the neonates with low Apgar scores, 6-4 and 3-0, were 172 +/- 74, 145 +/- 73 and 104 +/- 63, 92 +/- 55 U/l, respectively, which were significantly lower than those in the neonates with the high scores (10-7), 208 +/- 104, 183 +/- 92 U/l. The neonates with distress showed the low CK and CK MM values, 76 +/- 12 and 61 +/- 8 U/l. The CK and CK-MM levels of cord blood tended to decrease with prolongation of labor, but did not differ from each other among the neonates delivered by different modes. These results suggest that the CK and its isoenzyme levels are good indicators for the degree of maturity of neonates and the severity of neonatal distress. PMID- 1404963 TI - [Plasma lipid peroxides in the operation of esophageal cancer]. AB - Lipid peroxides are formed by autooxidation of polyunsaturated fatty acids found primarily in cell membranes. An increase level of lipid peroxides in the tissue therefore reflects membrane damage. We reported that water immersion restraint rats caused significant increase of gastric mucosal lipid peroxide which reflected on gastric mucosal injury. The gastric mucosal injury is also known as the post-operative complication due to physical stress. So we studied plasma lipid peroxide and its related substances in the operation of esophageal cancer. Lipid peroxide levels increased significantly in pre- and post-operation but temporal decrease was found during the operation. Vitamin E is thought to be an important structural component of biologic membranes and is believed to act as a free radical scavenger in lipid peroxidation. Vitamin E also increased in the patients of esophageal cancer and decreased significantly during the operation. Superoxide dismutase changed frequently during the operation but there was no deficit tendency in its changes. Catalase levels also changes frequently and showed temporal but statistical elevation after the operation. These results indicated that lipid peroxidation may contribute to the development of organic damage in the operation of esophageal cancer. PMID- 1404964 TI - [Endoscopic brushing cytology of esophageal lesions]. AB - Endoscopic esophageal biopsy and brushing cytology were performed simultaneously in 121 cases, 25 of which were diagnosed as esophageal cancer by histologic examination of surgically resected material or at autopsy. Correct diagnosis was made in 88% of the cancer cases by endoscopic biopsy, and the same diagnostic rate was obtained by brushing cytology. Combination of the two methods revealed the cancer in 96% of the cases. There were no cases diagnosed as false-positive or false-negative by cytology. Three cancer cases were diagnosed as suspicious by cytology. Definite diagnosis was not made because of paucity of cells on the slide or of cellular atypism. For the improvement of accuracy in cytologic diagnosis it is important to sample adequate amount of cells, and in situ carcinoma cells should be differentiated from benign atypical cells in esophagitis. PMID- 1404965 TI - [Rapid diagnosis of tuberculous lymphadenitis by amplification of mycobacterial DNA]. AB - In patients with cervical lymph node swelling, prompt differential diagnosis of tuberculosis leads to an appropriate treatment. A method based on DNA amplification and hybridization for the rapid detection of Mycobacterium tuberculosis was used for demonstrating its specific DNA in cervical lymph nodes biopsied from seven patients. The DNA specific for Mycobacterium tuberculosis was detected in 5 patients. Four of them were histologically diagnosed as tuberculous lymphadenitis. In another case with necrotizing lesions but without granulomatous reactions, culture method subsequently revealed a positive result. In other 2 cases, the diagnosis of tuberculosis was promptly excluded by both this method and conventional methods (histologic diagnosis/direct microscopy). The rapid detection of Mycobacterium tuberculosis by amplification of mycobacterial DNA is helpful particularly in differential diagnosis of cervical lymphadenopathy. PMID- 1404966 TI - [Event-related potential in patients with diabetes mellitus]. AB - The event-related potential (ERP) was recorded for 24 patients with diabetes mellitus (age 67.5 +/- 8.5 years, mean +/- SD) and 28 healthy controls (age 61.0 +/- 10.6 years) to elucidate the involvement of the central nervous system (CNS) in diabetes mellitus. ERP was recorded during auditory discriminative tasks. The latencies of N100, P200, N200 and P300 from the Pz region were measured. Patients with diabetes mellitus showed significant prolongation of N200 and P300 latencies compared with the normal subjects, while no significant differences in N100 and P200 latencies were found between the two groups. In six of 24 patients, the P300 latency delayed beyond the 2SD of the appropriate age-related value estimated from the normal regression line. The delay of the P300 latency was not related to either the duration of illness, therapeutic methods, or metabolic control. From the present results, it would appear that higher brain function is impaired even in diabetic patients not manifesting overt CNS signs and symptoms. PMID- 1404967 TI - [The 39th General Meeting of the Japanese Society of Clinical Pathology. Nagasaki, Japan, October 14-16, 1992. Abstracts]. PMID- 1404968 TI - [Effect of long-term administration of antisecretary drugs on rat gastric histamine synthesis and acid secretion--compare with omeprazole and cimetidine]. AB - To investigate the effect of 6 weeks administration of proton pump inhibitor (omeprazole) and H2-receptor antagonist (cimetidine) on gastric histamine synthesis and acid secretion, we studied experimentally in the rat stomach. Then gastric mucosal histamine concentration, histidine decarboxylase (HDC) activity and serum gastrin concentration, and HDC positive cell number were examined in time-course. The 6 weeks administration of omeprazole caused more increase of HDC positive cells than cimetidine. After cessation of administration with omeprazole, high plasma gastrin level immediately reduced. However the increase of gastric mucosal HDC activity and histamine concentration were prolonged, compared with cimetidine. These findings suggest to affect differently between omeprazole and cimetidine on gastric acid secretion after cessation of long-term treatment. PMID- 1404969 TI - [Morphological changes of extrahepatic bile ductal epithelia in hamsters feeded with lithogenic diet]. AB - Experimental cholelithiasis was established by feeding hamsters with lithogenic diet. Morphological changes of extrahepatic bile ductal epithelia were observed under light and electron microscopes at weeks 1, 2, 4 and 6 after the treatment. Moreover, the changes of mucus composition in goblet cells, which were located among the epithelia, were particularly evaluated using High iron diamin-Alcian blue pH 2.5 (HID-AB) stain. Compared with the controls, goblet cells of both superior bile duct (S-BD) and inferior bile duct (I-BD) increased in number, but more prominently in I-BD than in S-BD. Furthermore, goblet cells of the controls mainly contained sulfomucin positive for the HID in their cytoplasm. On the other hand, goblet cells of the lithogenic diet group mainly contained sialomucin negative for the HID in their cytoplasm. Electron microscopy demonstrated the extensive accumulation of secretory granules in the cytoplasm of the epithelial cells of both S-BD and I-BD. These results suggest that cholelithiasis may enhance the mucus secretion from extrahepatic bile ductal epithelia, and that the mucus oversecretion results in the protective effect on biliary epithelia. On the other hand, it is suggested that the mucus oversecretion may cause the bile retention in extrahepatic bile ducts, and also may have relation to the choledochitis or pancreatitis associated with cholelithiasis. PMID- 1404971 TI - [A case of early esophageal adenocarcinoma arising in Barrett's epithelium]. PMID- 1404970 TI - [Effects of urso-deoxycholic acid (UDCA) on alpha-naphthyl-isothiocyanate (ANIT) induced intrahepatic cholestasis in rats]. AB - Using the ANIT induced model of cholestasis in rats, the therapeutic effects of UDCA to the intrahepatic cholestasis were evaluated by changes of serum chemistry and liver histology. ANIT was administered once at a dosage of 40 mg/kg b.w. per os and UDCA was given ad libitum for 7 days by a drinking water containing UDCA at 0.5 and 5.0% solution. In the period of bile duct epithelial degeneration and necrosis, effects of UDCA for jaundice was not detected, but hepato-cellular disturbances were appeared histologically. Moreover, the elevation of serum levels of chenodeoxy-cholic acid, deoxycholic acid and lithocholic acid was accompanied. On the other hand, in the recovery stage of the bile duct epithelium, serum bilirubin was decreased significantly in the UDCA group which seemed to be related with the potent choleretic effect of UDCA. These results may indicate that UDCA is effective for the intrahepatic cholestasis in the case with no bile duct epithelial damage but in the presence of it hepato-cellular injury is introduced by the accumulated toxic bile acids in the blood. PMID- 1404972 TI - [A case of recurrent ischemic colitis associated with barium enema study]. PMID- 1404973 TI - A case of smoldering adult T-cell leukemia associated with duodenal dilatation due to strongyloidiasis. PMID- 1404974 TI - [A case of Sweet's syndrome with intrahepatic cholestasis]. PMID- 1404975 TI - [A case of gastric aberrant pancreas with pancreatic stone]. PMID- 1404976 TI - [Calcium-dependent signaling of acid secretion in isolated parietal cells from guinea pigs and its modification by ethanol]. AB - Treatment of isolated parietal cells from guinea pig gastric mucosa with ethanol caused a rapid increase in [Ca2+]i and concomitant decrease in the capacity for carbachol-stimulated acid secretion in a dose dependent manner. Carbachol rapidly increased the [Ca2+]i from trimethoxybenzoic acid 8-(diethylamino)-octyl ester sensitive intracellular pool. In contrast, the increase with ethanol was through La3+ sensitive Ca2+ channel from external source, which suppressed the Ca2+ response subsequently stimulated with carbachol. Pretreatment of the cells with EGTA or La3+ completely prevented the elevation of [Ca2+]i with ethanol and preserved the Ca2+ response to carbachol. These findings indicate that ethanol induced elevation of [Ca2+]i may desensitize the stimulation of carbachol. Furthermore, treatment of the parietal cells with ethanol increased the activity of protein kinase C in both cytosolic and membrane fractions of the cells. Activation of protein kinase C with phorbol diester suppressed the capacity for acid secretion. These results suggest that ethanol may inhibit the carbachol stimulated acid secretion through the desensitization of Ca2+ response and the activation of protein kinase C. PMID- 1404977 TI - [An experimental pathologic study of acute small intestinal ischaemic in mongrel dogs--occluded proximal site of anterior mesenteric artery by balloon catheter]. AB - We prepared experimental of small intestinal ischemia by occluding the inlet of the anterior mesenteric artery of adult mongrel dogs with balloon catheters. With these experimental models, the degree of tissue damage of the small intestinal mucosa, which became ischemic, was studied according to the different occlusion times of the anterior mesenteric artery (3, 5, 7, 10, 15 and 30 hours). As a result, ischemic mucosal lesions in the small intestine at an initial stage occurred on the antimesenteric side. In the gross findings of the mucosa when the occlusion time was within 5 hours, linear and spotted lesions appeared in a zone on the antimesenteric side. When the occlusion time was 7 hours or more, these lesions fused and the entire intestinal mucosa became a hemorrhagic lesion. By occluding the anterior mesenteric artery for 22-30 hours, all 6 experimental ischemic animals died. PMID- 1404978 TI - [Extraction efficacy on uptake of intraportally injected monoclonal antibody by human colorectal metastases in nude mice]. AB - Route of administration is an important determinant in tumor uptake of monoclonal antibody (mAb). We studied the extraction efficacy of intraportal injection (IP) on tumor uptake over time in hepatic metastases of human colon carcinoma (HT 29LMM) in nude mice. H-15, a murine IgG1 mAb reactive with HT-29LMM was labeled with I-125, and injected at dose of 0.1 microgram and 1.0 microgram intraportally (IP) or intravenously (IV). More than 3 animals per group were sacrificed immediately, 1 h, 24 h, 72 h, and 120 h following injection. Hepatic metastases, normal liver tissue, and blood were weighted and counted for radioactivity. Compared to IV, IP injection resulted in higher (P less than 0.01) percent injection dose per gram (%ID/g) in metastases at all time points for both doses. Metastases: blood and metastases: liver uptake ratios were higher (P less than 0.05) on day 3 and 5 for both IP doses compared to IV doses. Significant improvement in tumor uptake was seen following IP injection of specific mAb; this has important implications on the design of clinical trials using mAb. PMID- 1404979 TI - [Extracorporeal shock wave lithotripsy (ESWL) for common bile duct stones]. AB - We treated twenty-three patients with common bile duct stones (12 female, 11 male, mean age: 67.1 years) by Extracorporeal Shock Wave Lithotripsy (ESWL). The stones were focused by ultrasonic or choledochographic localization. The twenty three patients received 53 ESWL treatments consisting of mean 2357 shocks per treatment at mean 18 kV. We performed ESWL in five cases with endoscopically unextractable common bile duct stones after endoscopic sphincterotomy (EST). In these cases, ESWL permitted stone disintegration and successful endoscopic extraction of the fragments. We performed ESWL in eighteen cases with common bile duct stones without EST. In fifteen of the eighteen cases (83%), fragmentation was achieved. The stone fragments were spontaneously discharged in ten cases (56%) after a median of 4 days following ESWL. In five cases, adjutant endoscopic procedures were performed. The complete fragmentation and the clearance rate for stones of diameter of less than 10 mm were higher than that for stones of diameter of more than 11 mm. In the cases with the stones of diameter of more than 10 mm, there is a very strong possibility that complete clearance is achieved by ESWL alone. No correlation was obtained for the effective results according to pretreatment number of stones. In eight of thirteen cases (62%) with gall bladder stones, complete clearance was achieved without EST. ESWL without EST can be thought as a rational treatment for preserving the function of papilla of Vater in the case of cholecysto-choledocholithiasis. PMID- 1404980 TI - [Imaging diagnosis of the insulinoma--the clinical usefulness of intraductal ultrasonography of the pancreas and color Doppler sonography]. AB - 5 cases of small-sized insulinoma of the pancreas were studied to evaluate the ability of diagnostic imaging techniques to determine tumor location. Techniques used were extracorporeal ultrasonography, endoscopic ultrasonography (EUS), angiography, percutaneous transhepatic portal catheterization and CT. EUS was superior to the other modalities in diagnosing the location of insulinomas. We employed Color Doppler (CD) ultrasonography in one case and obtained color expression in the tumor and a pulsatile wave in the FFT analysis. Intraductal sonography of the pancreas (IDSP) was also performed in this case resulting peripheral echo-lucent, central echogenic mass. From these results, we expect that CD and IDSP will be useful in clinical application for diagnosing various tumors. PMID- 1404981 TI - [A case of hemangioma of the small intestine diagnosed by angiography]. PMID- 1404982 TI - [A case report of fibroepithelial polyp of the gallbladder]. PMID- 1404983 TI - [A case of splenic inflammatory pseudotumor]. PMID- 1404984 TI - [Epidemiology of non-ulcer dyspepsia (NUD) in Japan]. AB - The purpose of this study is to investigate the incidence of NUD in Japan and to describe the clinical presentation of NUD. The population of this study consisted of the patients initially visited to our gastroenterology clinic during the period of one year from Feb. 1990 to Jan. 1991. Out of the total population, 106 patients with dyspepsia were suspected of NUD according to the definition of AGA, and have received the endoscopy and ultrasonography to find the existence of organic disease. While 50 cases presented organic diseases (19 peptic ulcers, 16 gastritis, 7 carcinoma, 4 gall stone, 4 esophageal disease), 56 cases were with no organic diseases and were regarded as NUD. NUD was more common in younger generation and was especially so in women under 40 years old. There was no significant difference in symptoms between NUD and organic diseases. On the other hand, peptic ulcer disease was frequently associated with sever epigastralgia, and smoking habit as a external factor, while abdominal fullness was predominant feature observed in NUD. PMID- 1404985 TI - [Endothelin levels under water-immersion stress in rats]. AB - Rats with water-immersion stress-induced ulcer were prepared to determine the levels of ET in blood and gastric tissues, and their relationship with the gastric mucosal blood flow, PGs and pathogenesis in the gastric mucosa were evaluated. Pathology in the gastric mucosa appeared an hour after stress loading, while blood flow rate decreased significantly 30 minutes later. PGE2 increased 30 minutes later, then decreased. PGI2 decreased significantly. Blood ET level was 1.22 +/- 0.50 pg/ml for the controls, but this increased remarkably after one hour and significantly peaked after two hours of water immersion. The level of ET in the gastric tissues was 25.87 +/- 1.63 pg/g tissue for the controls, and this increased markedly after two hours of immersion, reaching a significant peak. In the present study, increased in endogenic ET due to stress were confirmed, and the results suggested the possibility of ET being involved in the pathogenesis of ulcer. PMID- 1404986 TI - [Hypergastrinemia and type A gastritis in Basedow's disease]. AB - Hypergastrinemia is a very important clinical condition for the reason that a growing body of evidence obtained from animal and human experiments has revealed gastric carcinoids induced by hypergastrinemia. We investigated 35 patients with Basedow's disease (BD) to elucidate the mechanism of hypergastrinemia associated with BD as well as the relationship between type A gastritis and BD. Fasting serum gastrin levels in BD (296.1 +/- 251.4 pg/ml; mean +/- S.D.) were significantly (p less than 0.001) higher than those in age-matched 27 healthy subjects (106.1 +/- 69.2), and in the BD group, significant positive correlation was detected between fasting serum gastrin levels and thyroid hormones (i.e. T3 and free T4). In the hyperchlorhydria group in BD with hypergastrinemia, the levels of fasting serum gastrin were normalized after euthyroidism was attained due to antithyroidal drugs. On the other hand, in the achlorhydria group in BD significant hypergastrinemia was persisted in spite of normalization of thyroid function. Twenty % of the BD patients had histologically proved type A gastritis with achlorhydria, and all patients with type A gastritis were older than 60 years old. Endoscopic examination revealed that one patient with type A gastritis had an early gastric cancer. However, no gastric carcinoids were demonstrated in this study. In conclusion, the results described as above suggested, 1) hypergastrinemia observed in patients with BD may be induced by gastrin hypersecretion due to hyperthyroidism as well as type A gastritis, 2) BD patients with type A gastritis were recommended to undertake regular endoscopic examination for detecting gastric cancers as well as gastric carcinoids. PMID- 1404987 TI - [Intracellular pH of surface epithelial cells and the movement of bicarbonate ions under acid-base imbalance in gastric mucosa]. AB - To investigate the effect of the acid-base imbalance on the gastric mucosal defense mechanism, the intracellular pH of gastric surface epithelial cells were measured with double-barreled H+ selective microelectrodes in the isolated antral mucosa of bullfrog stomach. By knowing the intracellular pH and the PCO2 of the serosal perfusate, the intracellular HCO3- concentration was estimated, and the rate of HCO3- secretion was directly measured with the pH-stat method in mounted preparations on a Ussing's chamber. Both the calculated intracellular HCO3- concentration and the rate of HCO3- secretion were dependent on the exogenous HCO3- supplied from the serosal perfusate. The alkaline tide raised the intracellular HCO3- concentration, thus increasing the mucosal buffering power against acid. Under mild respiratory acidosis, the production of endogenous HCO3- from the serosal CO2 was enhanced, and both the intracellular HCO3- concentration and the rate of HCO3- secretion were increased. As a result, the intracellular pH was maintained at a physiologically optimal level, and the ability of gastric mucosal protection was strengthened by enrichment of cellular bicarbonate supply. It is confirmed in this study that the maintenance of acid-base status in the cell is indispensable in the protection of gastric mucosa against acid invasion. PMID- 1404988 TI - [Clinical significance of measurement of PIIIP, laminin P1, type IV-C and 7S in patients with chronic liver diseases--with special reference to histological findings]. AB - Four markers for hepatic fibrosis--N-terminal peptide of Type III procollagen (PIIIP), Laminin P1 (laminin), Type IV collagen (Type IV-C), and 7S domain (7S)- were measured in the sera of 90 patients with various chronic liver diseases diagnosed by liver biopsy--fatty liver (FL), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), and liver cirrhosis (LC)--and in the sera of 20 healthy controls. The values of markers were compared with the grade of histologic findings of the liver. Four markers were significantly raised in the CAH group and the LC group, and they were considered to be indicators of hepatic fibrosis. PIIIP reflected necrosis and inflammation as well as fibrosis of the liver. Laminin, Type IV-C, and 7S reflected severe fibrosis. 7S was considered to be useful marker for liver cirrhosis. PMID- 1404989 TI - [Clinical evaluation of serum levels of monomeric dimeric and tetrameric pseudocholinesterases in patients with various liver diseases]. AB - Serum levels of monomeric, dimeric and tetrameric pseudocholinesterases were measured by means of enzyme-linked immunosorbent assay in patients with various liver diseases and normal controls in order to evaluate their clinical significance. In patients with liver cirrhosis, serum levels of monomeric, dimeric and tetrameric were significantly lower than those in normal controls, patients with fatty liver and chronic hepatitis. The ratio of monomeric and dimeric to tetrameric in patients with liver cirrhosis was also significantly lower than that in normal controls, patients with fatty liver and chronic hepatitis. Serum levels of tetrameric, dimeric and monomeric were not significantly higher in the patients with fatty liver than in normal controls, but the ratio of monomeric and dimeric to tetrameric was significantly higher in patients with fatty liver than that in normal controls, patients with chronic hepatitis and liver cirrhosis. These findings suggest that the selective determinations of serum levels of monomeric, dimeric and tetrameric pseudocholinesterases are useful to estimate the metabolism of fat and protein in various liver diseases. PMID- 1404990 TI - [Down-regulation of liver regeneration by LAK cells--a study for effect of neuraminidase treated LAK cells on liver regeneration]. AB - Both effect of LAK cells and neuraminidase treated LAK (N-LAK) cells on liver regeneration were investigated after 70% partial hepatectomy in mice. Intravenous transfusion of LAK cells suppressed the liver regeneration depending on cell numbers injected. N-LAK cells accumulated into regenerating liver 1.7 times in cell number compared with LAK cells. Injection of 5 x 10(7) LAK cells and N-LAK cells into hepatectomized mice suppressed the liver regeneration by 16.5% and 53.8% respectively. These results indicated that suppression of the liver regeneration by LAK cells was dependent upon the number of injected LAK cells and the degree of accumulation of LAK cells into the liver, namely, LAK cells down regulate the regeneration of liver cells in the micro-milieu. PMID- 1404991 TI - [Treatment of hemobilia after percutaneous transhepatic cholangiography and drainage (PTCD)]. AB - PTCD was performed in 206 of our patients during the past 6 years and 7 months. Of the 206, hemobilia occurred in 14 patients (6.8%). The hemorrhage was completely stopped by irrigation of the bile duct in 3 patients, compression with a larger catheter in 7 patients, and transcatheter anterior embolization (TAE) in 4 patients. TAE was performed on the patients whose hemobilia could not controlled by the compression with a larger catheter. In TAE, either a steel coil or a sponge was used as an embolus. Rebleeding occurred in one patients for whom the right hepatic artery was chosen as a embolization site. Therefore, it was decided that the embolization was going to be done in all the hepatic arteries when the blood stream in the portal vein and preserved functions of the liver of the subjected patients including the one with rebleeding were fully normal. A complete control of the hemorrhage was obtained in all patients. The PTCD root caused hemobilia was removed after TAE in considering the possibility of rebleeding from the root, and a new PTCD root was made. PMID- 1404993 TI - [A case report of unclassified ulcerative lesion of the jejunum causing massive melena]. PMID- 1404992 TI - [Studies on the influence of long-term doses of lipid peroxide generators on rat pancreas]. AB - The role of oxygen derived free radicals or tissue lipid peroxides in the pathogenesis of chronic pancreatitis has not been established. To evaluate long term effects of tissue lipid peroxides in the pathogenesis of chronic pancreatitis, we treated Wistar male rats with 2,2'-azo-bis-(2-amidino-propane) dihydrochloride (AAPH) and/or linoleic acid (LA) for 3 or 6 months. Rats were divided into eight groups. A: Saline-treated rats for 3 months as control, B: AAPH 40 mg/kgw intraperitoneally, twice a week for 3 months, C: LA 0.5 ml/kgw intraperitoneally, every other week for 3 months, D: AAPH and LA for 3 months, E: Saline-treated for 6 months, F: AAPH for 6 months, G: LA for 6 months, H: AAPH and LA for 6 months. The results were as follows: Lipid peroxide contents of the pancreas were elevated in groups: C, D, G and H. Histological examination revealed epithelial hyperplasia of large pancreatic ducts, vacuolization of ductal epithelium, intraepithelial neutrophilic infiltration, periductal mononuclear cell infiltration (ductulitis and peri-ductulitis), and sporadically in the lobules, destruction of acinar cells, neutrophilic infiltration and ductular proliferation in the same groups. These findings indicate that tissue damage was more severe in the pancreatic ducts than in the acinar cells, however no damage was seen in the endocrine pancreas. Vitamin E content of the pancreas was decreased in groups: B, C, D, F, G and H. Tissue glutathione peroxidase (GSH Px) activity was increased in groups: D and H. Tissue catalase activity was increased in groups: D, G and H, but no change of superoxide dismutase (SOD) activity was seen in any of the groups. These results indicate that vitamin E may play the role of the main scavenger in the situation of a smaller dose of lipid peroxides, but when larger doses are administered, GSH-Px may play the main role as the scavenger in this experimental system. PMID- 1404994 TI - [A case report of chronic idiopathic colonic pseudoobstruction]. PMID- 1404995 TI - [A case of metastatic Crohn's disease of the penis]. PMID- 1404996 TI - [An autopsy case of pseudomyxoma peritonei associated with high plasma levels of CA19-9 and CEA]. PMID- 1404997 TI - [A case of sulindac induced acute pancreatitis]. PMID- 1404998 TI - [Effects of isosorbide dinitrate on Oddi's sphincter]. PMID- 1404999 TI - [The 34th General Meeting of the Japanese Society of Gastroenterology. Utsunomiya, Japan, October 12-14, 1992. Abstracts]. PMID- 1405000 TI - [1992 meetings held by subsections of the Japanese Society of Gastroenterology. Abstracts]. PMID- 1405001 TI - [Industrialization and environmental protection--the approach to promotion environmentally development which maintains economic progress]. PMID- 1405002 TI - [Relationship between autoimmune diseases and pneumoconiosis]. AB - In recent years, with the aging of patients with pneumoconiosis, autoimmune diseases as a complication have been observed. One of the reasons for this may be that autoimmune diseases are prone to develop among the elderly. On the other hand, it has been reported that dust itself, such as silica for example, has adjuvant effect. A review of the recent literature published in Japan and abroad was made to clarify the relationship between pneumoconiosis and autoimmune diseases and the following results were obtained. 1) Disorders which accompany pneumoconiosis: Scleroderma, rheumatoid arthritis, systemic lupus erythematosus (SLE), and disorders of the kidney and liver have been reported. In Japan, about 30 cases of pneumoconiosis accompanied with autoimmune diseases have been reported. In many of the reports, patients with pneumoconiosis and scleroderma have a past history of exposure to silica. In both case studies and case control studies, patients with rheumatoid arthritis and history of silica exposure are prone to develop pneumoconiosis. 2) Immunological studies of patients with pneumoconiosis: As for humoral immunity, elevation of polyclonal gamma-globulin, especially IgG, has been often reported together with high positive rate of autoantibodies such as antinuclear antibodies. In cellular immunity, decreased delayed type skin reaction and decreased CD4/8 ratio have been reported. In human leukocyte antigen (HLA) typing the elevated frequency of DR4 has been reported. In the study of BAL increased production of superoxide anion O2- by alveolar macrophages has been observed. 3) EXPERIMENTAL STUDIES: Silica is well known for its toxicity to cells and also for its adjuvant effect. In the German Democratic Republic, patients with scleroderma and history of long term silica exposure are recognized as patients with occupational disease even though pneumoconiosis is not clearly demonstrated on X-ray film. It is difficult from this review to nrake a definite conclusion regarding the relation between silicosis and autoimmune diseases. There is a need to repeat this review of the literature on autoimmune diseases and pneumoconiosis in the near future. PMID- 1405003 TI - [Epidemiologic study on physical conditions related to work among the elderly]. AB - The present study was conducted in order to examine the epidemiologic factors related to work capacity among the elderly. As study area, Ogimi Village in Okinawa Prefecture was selected by reason of the long life expectancy of the inhabitants. Medical examination and interview were conducted on 756 inhabitants aged 65 yr and older. Working status was classified into two groups, that is, working group and non-working group. The association between working status and related factors was examined by using multiple logistic regression analysis. The examined factors were as follows: sex, age, history of apoplexy, history of being down, history of falls, history of fracture, chewing ability, pain, exercise habit, hobby, education, number of family members, alcohol, smoking, food intake frequencies and medical indicators (blood pressure, ECG, Quetlet index, skinfold thickness, grip strength, one-leg test with eyes opened, albumin, total cholesterol, hemoglobin and HDL-cholesterol). The results of the analysis revealed that grip strength and one-leg test with eyes opened had a statistically significant correlation with working status (p < 0.01). From the results, maintenance of muscle strength and equilibrium function were found to be the physical conditions related to work among the elderly in the agricultural area. PMID- 1405004 TI - [Effect of hydrolysis conditions on the determination of urinary 2,5-hexanedione in workers exposed or not exposed to N-hexane]. AB - In order to determine the optimal conditions of acid hydrolysis for urinary 2,5 hexanedione (HD) measurement, the effects of urine pH or volume of HCl added to urine and hydrolysis period were studied using gas chromatography-mass spectrometry (GC-MS). When 0.3 ml of concentrated HCl was added to 3 ml of urine, complete hydrolysis to liberate HD was attained 2 h after the start of heating at 100 degrees C for urine from non-exposed subjects. On the contrary, in urine from exposed subjects most of HD was liberated in 30 min at 100 degrees C, suggesting that the urinary substrates converted to HD by acid hydrolysis were different between exposed and non-exposed subjects. It was confirmed that hydrolysis for 2 h at 100 degrees C with 0.3 ml of concentrated HCl added to 3 ml of urine gave the most reliable levels and the greatest amounts of HD in both urine from exposed and non-exposed subjects. Reference values were determined by the hydrolysis conditions presented here. In 84 males, 52 females, and 136 with sexes combined the urinary HD levels were 0.35, 0.49, and 0.39 mg/l (geometric mean), respectively. Urinary HD levels determined without hydrolysis (free HD) were less than 0.006 mg/l in 31 control subjects examined. In urine from exposed subjects the amount of free HD was about one-fifth of the total HD (free plus conjugated HD) as determined with acid hydrolysates, although the percentage of free to total HD varied from 0.4 to 28%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405005 TI - [Utility of Mahalanobis distance in evaluating the results of health examination]. AB - A method using Mahalanobis distance (D2), the general probability distance in multivariate analysis, was studied for evaluating the results of health examination. D2 of each subject was computed by a personal computer with a BASIC program, and those whose D2 values lay out of 95% confidence interval were considered to be abnormal. In the present study, the mean value and standard deviation come from a normal range of Japanese, and the correlation coefficients between two items were obtained from blood donors in the hospital. These three parameters were necessary for calculation of D2. To examine the availability of this method, the data of a health examination on 370 new employees from 18 to 25 yr in age were analyzed with 9 items, including systolic pressure (SBP), diastolic pressure (DBP), serum glutamic oxaloacetic transaminase activity (GOT), serum glutamic pyruvic transaminase activity (GPT), serum gamma glutamyl transpeptidase activity (GGTP), serum total cholesterol (TCHO), serum triglyceride (TG), number of erythrocytes (RBC), and concentration of hemoglobin (Hb). It was shown that the data distributions of GOT, GPT, GGTP, and TG were log normal, and those of the other items were normal. With this method, 39 persons were also judged as abnormal from 46 subjects diagnosed to be abnormal by doctors, and the remaining 7 were missed but could be classed to be normal, as six of them had only slightly high levels of GPT (33-39 IU/l) and/or GGTP (42-57 IU/l), and one had a slightly high SBP (146 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405006 TI - [Sex difference of free erythrocyte protoporphyrin (FEP) level. III. Effect of estradiol on porphyrin metabolism, especially in FEP, in lead poisoned rats]. AB - An experimental study of sex hormone on FEP level in rats was conducted to clarify sex difference of FEP level. A total of 42 male Donryu rats were divided into 7 groups; group I (control 1; olive oil injection without castration), group II (control 2; olive oil alone), group III (EL; estradiol in olive oil, 50 micrograms/kg.BW), group IV (EH; estradiol in olive oil, 250 micrograms/kg.BW), group II' (Pb; Pb 5 mg/kg.BW), group III' (PbEL; Pb 5 mg/kg.BW + estradiol in olive oil, 50 micrograms/kg.BW) and group IV' (PbEH; Pb 5 mg/kg.BW+estradiol in olive oil, 250 micrograms/kg.BW). Excluding group I, all rats of the 6 groups were castrated. After one week from castration, estradiol was subcutaneously injected 4 times a week, and lead was intraperitoneally injected once a week for 6 wk. Estradiol suppressed growth, Ht, Hb value and liver function, but did not show any evident effect on FEP, ALA-U and CP-U. Erythrocyte ALA-D activity in group IV' (Pb+estradiol at high dose) showed a level higher than that in group II' (Pb-treatment alone). PMID- 1405007 TI - [Effect of swimming on the distribution of metallic mercury in mice]. PMID- 1405008 TI - [Visibility of fine asbestos fibers in transmission electron microscopy analysis]. PMID- 1405009 TI - [Replacement of fluid lost due to sweating in a hot working-environment]. AB - Replacement of fluid lost due to sweating in a hot working-environment was determined by measuring the body weight of 14 workers (53.6 +/- 7.1 years old) 5 times during a working day. They were engaged in repairing and/or maintaining blast furnaces in an environment of 27.9-42.6 degrees C in WBGT. The amount of fluid consumption from a free intake of either green tea and tap water or green tea, tap water and glucose-electrolyte solution (Pocari, Otsuka Pharmaceutical Co., referred to as G-E solution) was compared. The body weight loss during work was 1.70 +/- 0.70 kg when free intake of fluids plus G-E solution was allowed, while it was 1.60 +/- 0.65 kg when G-E solution was not allowed. Fluid intake with G-E solution was 1.03 +/- 0.35 l, and they could rehydrate 61%. Without the G-E solution fluid, was 0.75 +/- 0.37 l (47% rehydration). Fluid intake with G-E solution was significantly (p < 0.05) larger than that without it. The body weight difference between pre -ad post-work was significant (p < 0.001), i.e., it was 0.26 +/- 0.52 kg while drinking G-E solution and 0.52 +/- 0.53 kg without it. These results suggest that restoration of body fluid after thermal dehydration takes place much faster when consuming G-E solution. PMID- 1405010 TI - A sandwich enzyme immunoassay for liver-specific antigen and its forensic evaluation. AB - We attempted to develop a method for the determination of liver injuries, using a liver-specific antigen as a marker. The liver-specific antigen (LSA) was purified from the human liver and the antibody to the human LSA only reacted with the liver extract using the immuno-dot-blotting technique. Depending on the immunohistochemical study, the LSA was found to be located within the cytoplasm of hepatocytes. A sensitive and specific sandwich enzyme immunoassay was then developed for the measurement of LSA. The detection limit of human LSA was 1 fmol/tube (52 pg/tube) and this assay was not affected by hemolysis. The LSA levels in serum and blood from healthy subjects were distributed within a range below the detection limit. The LSA levels in the blood from cadavers whose livers had been damaged, were markedly elevated in comparison with the normal levels found in other cadavers (10-140 fold). No cross-reaction was observed with the liver extracts from several species (mouse, rat, guinea pig and rabbit). These results suggest that the measurement of LSA levels in blood will become a useful marker for the detection of liver injury. PMID- 1405011 TI - Further study of human salivary alpha-amylase polymorphism. AB - Genetic variants of salivary alpha-amylase were studied using isoelectric focusing in a pH gradient of 6-8 and silver staining methods. Five phenotypes which were tentatively named Amy1 N, Amy1 SN, Amy1 V1N, Amy1 V2SN and Amy1 V3N were detected. The phenotype frequencies in 371 unrelated Japanese were: Amy1 N = 94.33, Amy1 SN = 2.43, Amy1 V1N = 0.54, Amy1 V2SN = 0.27 and Amy1 V3N = 2.43%, respectively. Although variant bands of Amy1 V1N were detected by immunoblotting method using anti-human salivary amylase, those bands were not stained by starch iodine method for the detection of amylase activity. This suggested that a mutation was occurred in the region of amylase molecule which showed the activity. Amy1 V2SN comprised the production of three Amy1 genes and indicated the duplication of Amy1 gene. The individuals showing Amy1 V3N phenotype accorded with those showing amylase variant by PAGE. PMID- 1405012 TI - Beta-endorphin secretion at the time of sudden death due to cardiac or respiratory failure. AB - Using male and female Wistar rats, pituitary response to cardiac and respiratory failure type (CFT and RFT) sudden death caused by the intravenous administration of KC1 and SCC, respectively, was examined by analyzing variation in pituitary immunoreactive beta-endorphin (IR-beta-EP) levels determined by radioimmunoassay after death and in circulating IR-beta-EP levels during periods of agony. In the pituitary gland of both sexes which differed significantly in ratio of the organ weight to body weight for CFT and RFT (CFT greater than RFT), IR-beta-EP was significantly less in RFT than in CFT (p less than 0.05). No variation in plasma IR-beta-EP was noted during short periods of agony in CFT, but it markedly increased during long periods of agony in RFT. The highest elevation at 2 or 4 minutes after SCC administration was about 3 times the preadministration value for IR-beta-EP in males (p less than 0.01). But elevation in females was lower than in males. Rise plasma IR-beta-EP during agony of RFT is regarded to be of pituitary origin due to dexamethasone treatment. The pituitary was thus concluded to respond more to the fatal agony in RFT than in CFT. PMID- 1405013 TI - [Potentiation by carbon dioxide of carbon monoxide-induced death in the hypoxic condition]. AB - This study was aimed at clarifying the effect of carbon dioxide (CO2) on the toxicity of carbon monoxide (CO) in the hypoxic condition. In order to evaluate the coexistent toxicity of CO2 and CO under hypoxic hypoxia, we investigated the difference of CO toxicity between under the hypoxic and hypercapnic hypoxia in point of lethality in conscious male mice. Furthermore, we measured blood gases (pO2 and pCO2), pH, COHb concentration, and blood pressure (BP) and heart rate (HR) in urethane anesthetized male rabbits inhaled with 2 toxic gases: N2-toxic gas (O2 5.0%, CO 1.8%, N2 93.2%) and CO2-toxic gas (O2 5.0%, CO2 16.0%, CO 1.8%, N2 77.2%). The animals were inhaled with the 2 toxic gases until the BP reached 0 or 20 mmHg. In the latter case, when the BP reached 20 mmHg, the animals were inhaled with air and were intravenously infused with saline (20 ml/kg/30 min). Conscious mouse experiment: In the both types of hypoxia, LC50 were decreased with the decrease of O2 concentration and the LC50 of CO in hypercapnic hypoxia was significantly lower than that in nitrogen-replacement hypoxia in the range of 12% and 9% of O2 concentration in male mice. BP 0 mmHg-group experiment in rabbits: All the rabbits inhaled with N2-toxic gas or CO2-toxic gas died. The time to BP 0 mmHg in CO2-toxic gas group (7.8 +/- 0.33 min) was shorter than that in N2-toxic gas group (11.5 +/- 1.00 min). Although both toxic gases lowered pO2 level and elevated COHb% of the blood, CO2-toxic gas extremely elevated pCO2 level by 80-100 mmHg corresponding to lowering the serum pH by 0.37-0.45. BP was firstly elevated during 2-3 minutes by inhalation of these toxic gases and was finally lowered to die. HR decreased continuously after the inhalation of toxic gases until the animals died. BP 20 mmHg-group experiment in rabbits:Recoveries of COHb%, pCO2 level and pH of the blood in N2-toxic gas intoxication were significantly faster than those in CO2-toxic gas group. The times to COHb 10% were 64.2 min and 78.2 min in N2-toxic gas and CO2-toxic gas, respectively. But, there was no significant difference between N2-toxic gas and CO2-toxic gas intoxications in the recoveries of pO2 level, BP and HR. The above results suggest that CO2 potentiates the CO-intoxication under hypoxic hypoxia and our methods of coexistent gas toxicity may be useful for examining the gas toxicity in fire accident. PMID- 1405014 TI - [Trace analysis for drugs and poisons in human tissues]. AB - Despite continuous developments of analytical techniques in terms of sensitivity and accuracy, uncountable increase in number of chemical substances are brought into the field of forensic sciences to be analyzed. Based on the idea that progress in analytical technique to cope with the change of situation is always required, a research team including 10 members was organized to set up the most advanced methods at present to analyze the important drugs and poisons in biological materials for forensic purposes. Stimulant drugs such as methamphetamine and amphetamine were studied on the improvement of extraction procedure prior to mass spectrometric analysis. A conventional solvent extraction method was replaced by an extraction technique using Extrelut column. The technical procedure was simplified and the accuracy of measurement was improved. The changes in CO-Hb concentration in the whole blood in storage was examined with regard to the lapse of time and temperature, where a differential spectrophotometry was used. Useful information could be obtained from practical aspects. Analytical conditions of gas chromatography were revised on volatiles including alcohols, especially as to column conditions. The use of capillary column was recommended for sensitivity and peak separation. The optimum conditions for detecting barbiturates in the blood were examined. The combination of Sep-pak C18 cartridge with a capillary column for gas chromatography using nitrogen phosphorus detection was found preferable. Mass spectrometry of various kinds of local anesthetics was studied. Quantitative analysis of the drugs was examined on gas chromatography with a surface ionization detector. Three types of insecticides including organophosphorus, chlorinated and fluorine compounds were analyzed by gas chromatography/mass spectrometry in order to establish a sensitive and selective method. The detection limits, calibration and reproducibility were examined. Herbicide, paraquat, was examined on the sensitivity, recovery, required time and costs in connection with methods of pretreatment and analytical procedure. A secondary spectrophotometry was found useful practically. Antimony in biological tissues was analyzed, using a flameless atomic absorption spectrometer with carbon tube atomizer. The time for analysis was reduced, and sensitivity was improved. Immunoassay method was examined from general aspects on drugs and hormones. Using antibodies specific to haptens, the dynamics of such antigens as drugs and hormones in the body tissues were observed. Interfering substances at the time of toxicological analysis were checked in order to obtain reliable information. Exact identification was found possible by using gas chromatography/mass spectrometry. As described above, the research was made from the practical aspects of forensic toxicology, and meaningful results could be obtained from each study. PMID- 1405015 TI - [Reports on medico-legal data from massive investigation performed by the Medico Legal Society of Japan--weight and size of internal organs of normal Japanese today]. AB - A statistical study was made on the weight and size of internal organs of normal Japanese. The most of them were judicially autopsied by forensic pathologists all over Japan up to 1989. In these materials, the following cases were excluded; cases with long postmortem intervals, with diseases or damages to many organs, receiving therapeutic transfusion or infusion and cases of death by fire. In every case, the data was neglected when the organ itself had abnormality or damage, but the data from other organs were included. Thus, the total number of cases was 5,144, comprising 3,322 males and 1,822 females. The materials used are as follows; sudden natural death 941 cases (18.4%), death due to wound(s) 2,476 cases (48.4%), asphyxia 1,261 cases (24.7%), poisoning 257 cases (5.0%), death from cold 68 cases (1.3%), death due to burns 46 cases (0.9%) and others 62 cases (1.2%). The results obtained are presented in Table 1-12. PMID- 1405016 TI - Analysis of glycated albumin in postmortem blood samples as the diagnostic parameters of diabetes mellitus. AB - Glycated hemoglobin (GHb), fructosamine and glycated albumin (GA) in hemolytic sera from cadavers were analyzed for the postmortem diagnosis of diabetes mellitus. The levels of GHb and fructosamine were determined by boronate affinity chromatography and colorimetry, respectively. Albumin fraction was isolated from the samples by Affi-Gel Blue affinity chromatography. The glycated and non glycated molecules were separated by boronate affinity chromatography, and quantitated by bromcresol green method. Fructosamine could not be analyzed from highly hemolytic sera containing more than 10 g/l hemoglobin. In such samples, the levels of GHb and GA were deviated from the standard values, indicating their postmortem degradation. In less hemolytic samples, GA was as informative as GHb and fructosamine for the diagnosis of diabetes mellitus. PMID- 1405017 TI - [Identification of optical isomers of methamphetamine and its application to forensic medicine]. AB - In order to identify optical isomers (d and l-) of methamphetamine (MAMP), GC-MS analysis using optically resolvable reagent of N-trifluoroacetyl-L-prolyl chloride (L-TPC) and HPLC analysis using chiral cellulose-based columns were compared. In analysis of d- or l-MAMP (M) of TPC (T) derivatives by the GC-MS, contrary to the expectation that only d(M)-L(T) or l(M)-L(T) could be detected chemically, two diastereomers of d(M)-L(T) and d(M)-D(T) for d-MAMP and two of l(M)-L(T) and l(M)-D(T) for l-MAMP were demonstrated respectively. This results was attributed to a small percentage of D-TPC present in L-TPC. For racemic (dl) MAMP, none of these four isomers could be individually isolated, and they were detected as two overlapping peaks. In the HPLC analysis using chiral columns, d- and l-isomers of MAMP and amphetamine (AMP) could be clearly isolated with merely one analytical procedure, and the l/d ratio was possible to calculate with facility. From the rats urine administered d- or l-MAMP, only the corresponded optically active form of the administered drug was detected, and when racemic (dl)-MAMP was administered, d-MAMP, l-MAMP and their metabolites AMP were distinctly detected. The l/d ratio calculated from amount of MAMP and AMP excreted in rat urine within 24 hr was not in accordance with that of the administered dl-MAMP (l/d = 1.01): the l/d ratio was 0.45 for MAMP and 0.58 for AMP, and 0.50 for the total of MAMP and AMP. The similar results were observed in case of racemic (dl)-AMP. From several human specimens obtained from the cadavers dead by MAMP poisoning, only d-MAMP and the metabolite d-AMP were detected, and neither l-MAMP or l-AMP were demonstrated. In particular, a high concentration of d-MAMP was detected in gastric contents, brain, lung and liver. From the MAMP powder in possession, only d-MAMP was detected. These results suggest that this chiral column-HPLC procedure could be applied to medicolegal practice and forensic scientific investigation. PMID- 1405018 TI - [Investigation of algorithm for the calculation of probability of paternity likelihood using personal computer program, including the application to parentage testing in the decreased party]. AB - Algorithm for the computerized calculation of probability of paternity likelihood was investigated. The probability is calculated by Essen-Moller's formula as W = X/(X+Y) = 1/(1 + Y/X). The X value is also given as X = Hl, m, n/Kl, m, where kl, m and Hl, m, n are the probabilities of mother-child and mother-child-father combinations, respectively. In this study, four functions as F(PQ) = [1-(P not equal to Q)] x p x q, Z(RS) = (1- (R = S)), K(PQ,RS) = 1/2([(R = P) + (R = Q)].s + [(S = P) + (S = Q)].r).F (PQ)/Z(RS) and H(PQ, RS, TU) = 1/4([(R = P) + (R = Q)] [(S = T) + (S = U)] + [(S = P) + (S = Q)] [(R = T) + (R = U)]) x F(PQ).F(TU)/Z(RS) were created, where PQ, RS and TU were the genotypes of mother, child and the alleged father, P, Q, R, S, T and U were their alleles, and p, q, r, s, t and u were the allele frequencies. The equality or inequality in parenthesis was the relation operator which gave -1 or 0 when the expression was true of false, respectively. Then, three formulae as Y = n sigma k = l F([TU]k), Kl, m = 1 sigma i = l m sigma j = l K ([PQ]i, [RS]j) and Hl, m, n = l sigma i = l m sigma j = l n sigma k = l H([PQ]i, [RS]j, [TU]k) were obtained, where [PQ]i, [RS]j and [TU]k were one of the mother's, one of the child's and one of the putative father's genotypes considered from their phenotypes, respectively. Using these formulae, the probability of paternity likelihood could be calculated in every case. These formulae were programmed in BASIC language using a personal computer. Algorithm for the calculation of the probability in the deceased party was also investigated. PMID- 1405019 TI - [Three cases of acute methamphetamine intoxication--analysis of optically active methamphetamine]. AB - Three typical cases of acute methamphetamine intoxication are reported. The concentrations of methamphetamine in the blood were 27.2, 6.43 and 0.60 micrograms/ml, respectively. All three victims had been exposed to high temperature in a bathroom or a closed room in summer at the time of death. Macroscopic autopsy revealed hemorrhagic pulmonary edema, and histologically, diffuse contraction-band necrosis was evident in the myocardium in all cases. The absolute structures of six illegally available methamphetamine showed an (S) configuration with an optical purity of > 99% in enantiomeric excess and four were racemic form. PMID- 1405020 TI - [Analysis of thinner components using the Curie-point pyrolyzer-gas chromatographic method in the tissues of a victim fatally poisoned]. AB - A 43-year-old male was found dead in the trunk of his car which was filled with thinner vapor. Thinner components in the tissues were analyzed using a gas chromatograph equipped with Curie-point pyrolyzer (Py-GC), and a gas chromatograph-mass spectrometer. The Py-GC method was able to analyze with very small materials. It was simple and quick but not as sensitive as the head-space gas chromatographic method. Toluene, ethylbenzene and xylenes were detected in the tissues, and their presence was confirmed by gas chromatography-mass spectrometry. The concentrations of toluene, ethylbenzene and xylenes in blood and the brain were 56.8, 6.8 and 4.5 micrograms/ml; and 203, 43.5 and 33.9 micrograms/g, respectively. The cause of death was thus judged as be thinner poisoning. PMID- 1405021 TI - [A fatal case caused by organophosphorus insecticide intoxication and confirmed by the metabolite found in the blood]. AB - An 83-year-old woman and two other members of her family were poisoned after eating lettuce prepared with Ethimethon Granule 6 instead of salt by mistake. Ethimethon Granule 6 is a mixture of organophosphorus pesticides, disulfoton and diazinon. All three were admitted to a hospital, and she died 22 h after ingestion and the others recovered. Disulfoton and diazinon in the remaining lettuce were detected and confirmed by gas chromatography-mass spectrometry. The pesticides, however, were not detected in the blood sample collected from the victim at autopsy. A metabolite of disulfoton, phosphorothiolate sulfone, was detected by FPD-gas chromatography, and confirmed by gas chromatography-mass spectrometry. PMID- 1405022 TI - [A case of suicide by an intravenous injection of pancuronium]. AB - A 25-year-old male anesthesiologist was found dead in his room with an intravenous drip line connected with his leg. There were several empty ampules of pancuronium, midazolam and buprenorphine around him. Pancuronium and midazolam in the blood and urine samples collected at postmortem examination were detected by spectrofluorometry and ECD-gas chromatography, respectively. The concentrations of pancuronium and midazolam were 0.3 micrograms/g and 0.12 micrograms/g in the blood, respectively; 0.9 micrograms/g and 0.05 micrograms/g in the urine, respectively. The cause of death was determined to be asphyxia due to respiratory muscle paralysis caused by pancuronium. PMID- 1405023 TI - [Research on nursing of bedridden elderly persons (1). Framework on nursing and nursing research on bedridden old persons]. PMID- 1405024 TI - [Research on nursing of bedridden elderly persons (1). Concerning the terminology of "the bedridden old persons"]. PMID- 1405025 TI - [Research on nursing of bedridden elderly persons (1). "Bedridden and bed-bound" and ADL as their assessment]. PMID- 1405026 TI - [Research on nursing of bedridden elderly persons (1). The review concerning fact finding of bedridden and/or housebound elderly in Japan]. PMID- 1405027 TI - [Research on nursing of bedridden elderly persons (1). Epidemiological studies on "bedridden period prior to death" in the elderly]. PMID- 1405028 TI - [The descriptive study of quality of life among men in living with chronic ischemic heart disease: analysis on the aspects of daily life control and sexuality (4)]. PMID- 1405029 TI - [A study of the function of nurse counseling: a phenomenological analysis of the counseling processes with hemodialysis patients (1)]. PMID- 1405030 TI - [Approach to the research references in foreign languages. Analysing and composing articles (2)]. PMID- 1405031 TI - Inhibitory reflex during bronchoconstrictions induced by histamine and Ascaris suum antigen. AB - We investigated the involvements of sympathetic and nonadrenergic nervous systems in the inhibitory reflex following bronchoconstriction in dogs. Inhalations of a 0.00125% solution of histamine and Ascaris suum antigen (3 mg protein) to the bronchial side induced reflex tracheal constriction following bronchoconstriction. An intra-arterial infusion of 5 micrograms/min of atropine to the tracheal site changed the reflex tracheal constrictions by histamine and antigen inhalations into tracheal dilatations. The reflex tracheal dilatations were abolished by the combination of intra-arterial propranolol (100 micrograms) and transections of both the bilateral superior laryngeal nerves and the spinal cord at the C1 level. The reflex tracheal constrictions induced by histamine and antigen inhalations were increased with 100 micrograms propranolol. Furthermore, the reflex tracheal constrictions were enhanced by the combination of 100 micrograms propranolol and transection of the spinal cord. These findings indicate that during the constriction of the bronchial smooth muscle, not only a reflex tracheal constriction mechanism but also one of reflex dilatation operates and that the latter reflex response may be mainly mediated by the sympathetic nerves, with partial involvement of the nonadrenergic nerves. This inhibitory reflex may attenuate asthmatic bronchoconstriction. PMID- 1405032 TI - Peptide leukotriene antagonistic activity of AS-35, a new antiallergic drug. AB - The effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5 yl)-4H-pyrido[1,2-a]pyrimidin-4-one (AS-35), a newly synthesized compound, on leukotrienes (LTs) antagonistic activities were investigated in vitro and in vivo. In isolated guinea pig preparations, AS-35 antagonized LTC4-, LTD4- and LTE4-induced contractions of the ileum with IC50 values of 8 nM, 4 nM and 3 nM, respectively. In the trachea, the agent also antagonized LTD4- and LTE4-induced contractions with IC50 values of 10 nM and 20 nM, respectively. However, LTC4 induced tracheal contraction in the presence of L-serine borate was not antagonized by AS-35. Histamine-, acetylcholine-, serotonin- and bradykinin induced contractions of the ileum, carbachol-, prostaglandin D2-, prostaglandin F2 alpha-induced contractions of the trachea and LTB4-induced chemotaxis of rat polymorphonuclear leukocytes were not inhibited by AS-35. As to the in vivo models, AS-35 (i.v.) dose-dependently antagonized bronchoconstriction induced by i.v.-injection of LTC4 and LTD4 in anesthetized guinea pigs, but did not inhibit histamine-induced bronchoconstriction. Oral administration of AS-35 also antagonized LTD4- as well as antigen-induced LT-mediated bronchoconstriction. In addition, LTD4-induced increase in the cutaneous vascular permeability of guinea pig was inhibited by the drug (p.o.). These results indicate that AS-35 is an orally effective, potent and selective peptide LT antagonist. PMID- 1405033 TI - Inhibition of radiolabeled leukotriene-binding by AS-35 in guinea pig lung membrane fraction. AB - The inhibitory effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (AS-35), a peptide leukotriene (LT) antagonist, on specific bindings of radiolabeled LTC4 and LTD4 in guinea pig lung membrane were investigated to clarify the mechanism by which this agent inhibited LT-induced physiological responses. Binding assays were performed at 20 degrees C in 50 mM Tris-HCl buffer (pH 7.4) containing 10 mM CaCl2, 10 mM MgCl2 and 10 mM cysteine in the absence (LTD4 binding assay) or presence (LTC4 binding assay) of 80 mM L-serine borate. Scatchard analysis of each LT specific binding indicated a single and high affinity binding site with a Kd of 0.21 +/- 0.05 nM and Bmax of 808 +/- 71 fmol/mg protein for [3H]-LTD4, and with a Kd of 21.6 +/- 3.8 nM and Bmax of 74.9 +/- 2.6 pmol/mg protein for [3H]-LTC4. Competition binding studies showed that AS-35 antagonized [3H]-LTD4 specific binding with a Ki value of 92.7 nM. In contrast, AS-35 was 100 times less effective in inhibiting [3H]-LTC4 specific binding, compared with [3H]-LTD4 specific binding. These results indicate that AS-35 interacts directly with peptide LTs receptors, especially the LTD4 specific binding site to produce its pharmacological effects. PMID- 1405034 TI - Improvement of drug-induced cardiac failure by NKH477, a novel forskolin derivative, in the dog heart-lung preparation. AB - The efficacy of NKH477, a novel water-soluble forskolin derivative, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital, propranolol or verapamil so that cardiac output had been reduced by about 40-50% of the respective control were all improved by NKH477 (10-100 micrograms) in a dose-dependent manner. With 100 micrograms NKH477, almost complete restoration of cardiac performance was attained in the respective cardiac failures. In the combination of NKH477 with ouabain (30 micrograms), 30 micrograms of NKH477 completely restored the cardiac function depressed by pentobarbital, associated with a slight but not significant increase in heart rate. No arrhythmias were induced by any of the NKH477 doses used in the experiments. These results suggest that NKH477 should be subjected to clinical trials in the treatment of cardiac failure. PMID- 1405035 TI - The contraction mechanisms for norepinephrine in single cells prepared from tracheal smooth muscles of guinea pig of different ages. AB - Single cells were prepared from guinea pig tracheal smooth muscle and used in an experiment on the contraction mechanisms for norepinephrine and a study on the change of alpha 2-adrenoceptors with age. Specific bindings of [3H]p aminoclonidine to the single cells from the tracheal smooth muscles of 6- and 40 week-old guinea pigs were saturable and analyzed by Scatchard plot. The maximum number of [3H]p-aminoclonidine binding sites was larger in the preparation from 40-week-old guinea pigs than that from 6-week-old animals, while its dissociation constant did not change with age. The amount of prostaglandin F2 alpha released from the single cells was increased by norepinephrine, not affected by phenylephrine, and reduced by an alpha 2-antagonist such as yohimbine. The amount released by norepinephrine was significantly larger in the preparation from 6 week-old guinea pigs than that from 40-week-old animals. These results suggest that the age-related decrease in the potency of norepinephrine is due to reduction in the amount of excitable prostaglandin F2 alpha released by the drug, but not to a change in the total amount of alpha 2-adrenoceptors or the dissociation constant of the drug with respect to these adrenoceptors. Furthermore, alpha 2-adrenoceptors in the tracheal smooth muscle cell play an important role in the release of prostaglandin F2 alpha and the production of contractile responses of these muscles. PMID- 1405036 TI - Inhibition of gastric glucosamine synthetase activity by oxygen radicals: a possible cause of decreased mucosal protective capacity. AB - To clarify the role of oxygen radicals in the mucus metabolism of the gastrointestinal tract, the effect of oxygen radicals on the activity of glucosamine synthetase, the rate-limiting enzyme of mucus synthesis, was investigated using homogenate derived from rat gastric mucosa. The simultaneous addition of both xanthine and xanthine oxidase caused a significant inhibition of the enzyme activity, and this decrease was counteracted by catalase, but not by superoxide dismutase. Hydrogen peroxide also caused a significant decrease in the enzyme activity; and this effect of hydrogen peroxide was counteracted by catalase and dithiothreitol, but not by mannitol, dimethyl sulfoxide and reduced glutathione. The inhibition of glucosamine synthetase activity by oxygen radicals is considered to be caused by the oxidation of sulfhydryl groups of the enzyme molecule. The present results also suggest that oxygen radicals in the gastrointestinal tract may induce the suppression of a protective mechanism of the gastric mucosa by inhibiting glucosamine synthesis activity. PMID- 1405037 TI - Neurochemical investigation on the effects of a new diphenylpiperazine calcium antagonist, KB-2796, on the central dopaminergic system of rats. AB - The effects of KB-2796, a new diphenylpiperazine calcium antagonist, on the striatal dopaminergic system of rats were investigated in comparison with various calcium antagonists and the dopamine antagonist chlorpromazine. The inhibiting effect of KB-2796 on [3H]spiperone binding to striatal membranes in vitro was weaker than those of chlorpromazine and the other diphenylpiperazine analogues, flunarizine and cinnarizine, and more potent than those of verapamil and nicardipine. Diltiazem and nifedipine were inactive. KB-2796 (30, 100 mg/kg, p.o.) had no effect on Kd and Bmax values of in vitro [3H]spiperone specific binding to striatal membranes obtained from the rat at 36 hr and 7 days after repeated administration for 18 days, whereas flunarizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased Bmax values by 47% and 31%, respectively, at 36 hr, but not at 7 days after the final administration. At 1 hr after the single administration, KB-2796 (30, 100 mg/kg, p.o.) had no effect on the content of dopamine and its metabolites in the striatum, whereas flunarizine (30 mg/kg, p.o.) and chlorpromazine (3 mg/kg, p.o.) increased the level of homovanillic acid. These results indicate that flunarizine may affect dopaminergic neurotransmission by partially blocking dopamine D2 receptors, while KB-2796 has negligible in vivo effect on the dopaminergic system. PMID- 1405038 TI - Different pathways for Ca2+ influx and intracellular release of Ca2+ mediated by muscarinic receptors in ileal longitudinal smooth muscle. AB - Muscarinic receptor-mediated elevations in intracellular Ca2+ concentration ([Ca2+]i) in the longitudinal smooth muscle of guinea pig ileum were studied by the use of fura-2 fluorescence. Dose-response analysis indicated a difference in the potencies of carbachol (CCh) to increase [Ca2+]i in the presence and absence of extracellular Ca2+. For the increase in [Ca2+]i due to Ca2+ release from intracellular stores in the absence of extracellular Ca2+, the ED50 value of CCh was 3 x 10(-5) M. On the other hand, in the presence of Ca2+, the ED50 value was 2.5 x 10(-7) M, indicating that a low concentration of CCh (less than 10(-7) M) caused influx of extracellular Ca2+ without Ca2+ release. Oxotremorine and pilocarpine induced Ca2+ influx, but were less potent inducers of Ca2+ release. CCh also stimulated the formation of inositol trisphosphates (IP3) with an ED50 value of (4.5 x 10(-5) M), which was similar to that for Ca2+ release from intracellular stores. Treatment of the smooth muscle with neomycin (1 mM), a phospholipase C inhibitor, abolished both CCh-induced IP3 formation and Ca2+ release from intracellular stores, but did not affect CCh-induced Ca2+ influx. These results suggest that the pathway for muscarinic stimulation of Ca2+ influx through plasma membranes is different from that for Ca2+ release from intracellular stores, which seems to be coupled with IP3 formation. PMID- 1405039 TI - Effect of Ca2+ antagonists on high-K+ evoked increase in [Ca2+]i in rat cerebral synaptosomes and hippocampal neurons. AB - By fura-2 fluorometry, we investigated the direct effects of Ca2+ antagonists including a new benzothiazepine, clentiazem, on the high-K(+)-evoked increase in the concentration of cytosolic free Ca2+ ([Ca2+]i) in rat cerebral synaptosomes and cultured hippocampal neurons. In both preparations, metal ions inhibited the high-K(+)-induced increase in [Ca2+]i, in the following order: La3+ greater than Cd2+ much greater than Ni2+. Although flunarizine and nicardipine inhibited the K(+)-induced increase in [Ca2+]i in synaptosomes, other Ca2+ antagonists, including clentiazem and nitrendipine, had little effect at 10 microM. In hippocampal neurons, clentiazem inhibited the K(+)-induced increase in [Ca2+]i at 10 microM, as did flunarizine and nicardipine. However, nifedipine and nitrendipine had little effect in either cultured neurons or in synaptosomes. PMID- 1405040 TI - Circadian rhythm of plasma uric acid and handling stress-induced hyperuricemia in conscious cebus monkeys. AB - An apparent circadian rhythm of plasma uric acid and the effect of handling stress on plasma uric acid level in conscious cebus monkeys were demonstrated. The lowest level of plasma uric acid in the circadian rhythm occurred early in the morning and the highest, before bedtime at night. With experimental handling stress, the plasma uric acid level rose to much more than the maximum level of the circadian rhythm. Stress-induced hyperuricemia could be inhibited without an increase of urinary uric acid excretion by the minor tranquilizer diazepam at doses of more than 1 mg/kg, p.o. On the other hand, benzbromarone at 20 mg/kg, p.o. significantly inhibited the hyperuricemia with a hyperuricosuric effect, while probenecid at 50 mg/kg, p.o. had no effect on either the increased plasma uric acid or urinary uric acid excretion. Accordingly, it is concluded that the plasma uric acid level in conscious cebus monkeys easily fluctuates with experimental conditions and that the animals can be utilized to evaluate the hypouricemic and hyperuricosuric property of benzbromarone-like agents. PMID- 1405041 TI - The effect of nilvadipine, a dihydropyridine type calcium channel blocker, on local cerebral blood flow in rats. AB - The effect of nilvadipine, a dihydropyridine type calcium channel blocker, on local cerebral blood flow (lCBF) was investigated using the autoradiographic iodo[14C]antipyrine technique in rats. In control rats, lCBF in cortical areas and in the superior colliculus and inferior colliculus was higher than that in the hippocampus, septal nucleus, globus pallidus and substantia nigra. Nilvadipine (32 micrograms/kg, i.v.) increased lCBF in all structures (significantly in 11 of 21 structures) in spite of a 33% reduction in mean arterial blood pressure. These results confirm that nilvadipine has the ability to increase cerebral blood flow. PMID- 1405042 TI - Influence of adrenalectomy on chronopharmacological phenomenon of furosemide in rats. AB - The role of adrenal corticoids in the time-dependent changes in the effects of furosemide was examined. Furosemide (30 mg/kg) was given orally to adrenalectomized or sham-operated rats at 12 a.m. or 12 p.m. Urine volume and urinary excretion of sodium and furosemide for 8 hr were significantly greater at 12 a.m. than at 12 p.m. in the sham-operated rats. However, such time-dependent changes in these parameters disappeared in the adrenalectomized animals. These findings indicate that adrenal corticoids are directly or indirectly involved in this event. PMID- 1405043 TI - [The influence of significant others on the formation of own self-image]. AB - This study aims to verify how other persons influential for the formation of own self-image change during the period from pre-adolescence to early adolescence, and what sorts of dynamism operating among the self-image, self-image assumed by others (reflected self-image: RS), and the images of others (objective self image: O). A SCT questionnaire was administered to altogether 370 students of both sexes in 4th, 5th and 6th grades and freshman and sophomore year of junior high school. The significant others were identified on the bases of similarity between individual own self-image and ones assumed by others. All descriptions were classified as positive, negative or other, and the inter-relationships among them were examined. Findings were as follows: 1) Though the significant others in this period did not necessarily shift from their parents to chums, males were most susceptive to others' influence in the 6th grade, while females seemed to have already established their own self-images insusceptive to others by this age. 2) The significance of chums was confirmed for males throughout their school years. For females, however, no such trend was found, suggesting that any particular significant person would either appear in a later year or never be identified. PMID- 1405044 TI - [The effects of individual differences on self-evaluation maintenance model]. AB - This study was conducted to examine the effects of individual differences in affiliation motivation, achievement motivation, and self-esteem on the self evaluation maintenance (SEM) model proposed by Tesser et al. (1984). One hundred and seventy college students answered a questionnaire for measuring affiliation motivation, achievement motivation, and self-esteem, and also assessed their own as well as their friends' academic achievements in their senior high school subjects with both high and low degrees of relevancy. For those who were high in affiliative motivation, a significantly greater difference between the own and the friends' achievements was found in the academic subjects with low rather than high relevancy. However, the same difference was also greater in the academic subjects with low rather than high relevancy for those who were low in their achievement motivation or self-esteem. These results suggest that individual differences in some variables such as affiliation motivation, achievement motivation, and self-esteem would play an important role in the SEM model. PMID- 1405045 TI - [The effects of fear on individual and group escape in a computer simulated maze]. AB - The purpose is to compare the effects of fear on escape behavior of individual and group conditions, in a computer-simulated maze. CRT display did not provide a bird's eye view of the maze, to the subjects, but only cues, what they would see, if they were actually inside of the maze. In the group escape condition, bodies and behaviors of other people were also shown in the maze. Subjects often got too close each other and collided with each other. THE RESULTS: Fear increased the time and locomotion required to reach the exit, because of the occurrence of a "traffic jam" in the group escape condition, however, fear reduced time in the individual escape condition. In addition, fear influenced types of escape behavior, depending on the form of maze. PMID- 1405046 TI - [Structure and functions of self-recognition need in adolescent women]. AB - The purpose is to propose a construct of self-recognition need, and to elucidate structure and functions of the need in adolescent women. First, 242 female subjects (average age 19.0) responded to a questionnaire. The results were factor analyzed to construct two scales of the need: self-recognition need scale and escape from negative information need. Inquiring these scales and their relation with maladjustment in daily life, the higher the maladjustment, the stronger their self-recognition need. In the second survey, 236 female subjects (average age 18.9) responded, RESULTS: (1) subjects with stronger self-recognition approached positively to many information seeking (even when they expect negative information about themselves), (2) self-recognition need showed positive correlation with motivation for praise acquisition and rejection avoidance. The implication of these results were discussed. PMID- 1405047 TI - [The effects of meaning information on heart rate, respiration, frontalis EMG, and peripheral temperature during imagery]. AB - The present study investigated the effects of meaning information on psychophysiological responses during imagery. Eighteen undergraduates were divided into arousal and relaxation groups, which were then given arousal-meaning and relaxation-meaning-oriented trainings, respectively. After the training, the subjects were given the imagery test, and inter-heartbeat-interval (IBI), respiration, frontalis EMG, and peripheral temperature during neutral, snake, and social imageries were analyzed. The results showed that there was a significant main effect in IBI for groups: the arousal group demonstrated greater IBI changes than the relaxation group. Regarding EMG, significant increases were present during snake and social imageries in the arousal group, whereas no significant increase was observed in the relaxation group. No significant difference between groups was found in respiration and temperature. The results suggest that there are some situations that accompany their primary meanings, and that meaning oriented trainings can modify the structure of the response propositions. PMID- 1405048 TI - [The effects of role playing on prosocial behavior in preschool children]. AB - The purpose was to examine the effects of two types of role-playing experience on prosocial behavior in preschool children. Subjects were 72 6-year-olds. In the Empathy role-playing (E), each pair of children enacted alternately a victim and an eyewitness using a glove puppet, in which the emphasis was only on empathizing with the victim. In the Empathy and Helping role-playing (EH), they enacted alternately a victim and a helper, in which the emphasis was on empathizing and helping a victim. In the Control role-playing (C), they played roles alternately of a customer and a salesman in a grocery store. All children were assessed as for helping and sharing behaviors for a real victim before and after the role playing session. In the comparison between pre- and post-tests for helping behavior. All groups (C, E, EH) increased helping tendency, but only in EH group the proportion of subjects, whose attitude changed from helper to non-helper. As for sharing behavior, all three groups increased the number of sharing significantly in the post-test. PMID- 1405049 TI - [A study of revised self-monitoring scale]. AB - The present study attempted to construct the Japanese version of Revised Self Monitoring Scale (Lennox & Wolfe, 1984). Factor analysis of this scale yielded two factors: 1) Sensitivity to expressive behavior of others, 2) Ability to modify self-presentation. This scale and its two factors had acceptable internal consistency: these results were almost similar with the original study. In correlational analyses with other personality measures, this scale correlated positively with both Private and Public Self-Consciousness Scale and Maudsley Personality Inventory-E Scale, but positively or negatively with some scales of Yatabe-Guilford Personality Inventory (e.g., G, S: positively. I, T: negatively.). Moreover the correlations between the two factors and the above mentioned measures provided interesting results. The availability of this scale was discussed. PMID- 1405050 TI - [Type A personality and level of aspiration in preschool children: some basic characteristics of aspiration levels and their modifications by introducing risk taking and competitive situations]. AB - The purpose of this study was to investigate some characteristics of aspiration levels of Type A preschoolers. Twenty-two Type A and twenty-one Type B subjects selected from 245 preschoolers were given three tasks: ball-throwing task 1, ball throwing task 2, and ringtoss task. After investigating some basic characteristics of aspiration levels in a standard situation (ball-throwing task 1), risk-taking (ball-throwing task 2) and competitive (ringtoss task) situations were introduced in order to study the modifications of aspiration levels. The results indicated that Type A children showed higher aspiration levels than Type B children, but that no differences of changes in aspiration levels by introducing risk-taking and competitive situations were found between the two types. These results were discussed from the view point of formation of Type A characteristics. PMID- 1405051 TI - [Retrieval of faces from features described by eyewitnesses]. AB - This experiment proposes a computer technique to find a witnessed one in the database of faces, from an eyewitness's feature description. The method is basically to choose the face with maximum likelihood for an eyewitness's description. The likelihood is derived from one of three models, in which the description of a features by a witness is based on either (i) judgement through all features, (ii) feature sampling with replacement, or (iii) feature sampling without replacement. Three models were assessed by free description task of facial features. RESULTS: these three models showed sufficient accuracy of retrieval, and the feature sampling without replacement model was superior to other two models. PMID- 1405052 TI - [An examination of two distinct aspects of anxiety in adolescence]. AB - This study aimed at measuring and examining two aspects of anxiety in adolescence. After reviewing previous studies, it was hypothesized that anxiety concept has a positive aspect of human growth promotion in addition to a negative aspect of growth inhibition. In Study I, 20 preparatory items for both positive and negative anxiety were administered to 817 high school students with three other scales relevant to human growth: "purpose in life", identity dimension, and self-concept. Ten positive anxiety items and 15 negative items were selected, referring to pattern of factor loadings. These two anxiety scales were validated using three reference scales and responses of 12 neurotic clients as standards, and the mutual independence of two aspects was confirmed. In Study II, the characteristics of two aspects of anxiety in adolescence were examined, using the data of 817 high school students and 379 undergraduates. It was found that the level of positive anxiety increased through high school years, reaching a peak in freshman year, while the negative anxiety remained about the same level in the same period. PMID- 1405053 TI - [Effects of leader behavior on subordinate's upward influence tactics and relationship between subordinate and leader]. AB - This study aimed at examining the upward influence tactics employed by subordinates toward their immediate superiors (the leader) in relation to the cohesiveness of a given group, leadership behavior on the part of the leader, and leadership behavior on the part of the group's top leader. The survey involved a sample of 120 nurses. Each nurse was asked to complete a questionnaire, which was prepared on the basis of an earlier preliminary study. The results of the group survey were as follows: (1) A nurse (the subordinate) generally gave play to the tactics of rationality and enthusiasm vis-a-vis a democratically inclined head nurse (the immediate superior); (2) coalition behavior was widely practiced in groups that were highly cohesive, while higher authority was employed vis-a-vis a democratically inclined top head nurse (the top leader); (3) the above-mentioned actions employing tactics of influence [(1) to (2)] had, in turn, an effect on the degree of response on the part of the head nurse (the leader) and on the ex post factor relationship between the two parties (nurse and head nurse). PMID- 1405054 TI - [Self-disclosure and loneliness]. AB - This study examined the relationship between self-disclosure and loneliness. The self-disclosure questionnaire (ESDQ) and the loneliness scale (LSO, consists of two subscales, U-scale and E-scale) were administered to 114 female subjects (junior college students). Results show that self-disclosure scores were negatively related to the U-scale of loneliness (whether or not they believe in mutual sympathy among human beings), but not to the E-scale of loneliness (whether or not they are conscious of individuality of each individual). The results suggest that we have to specify the quality of loneliness in question, when we examine the relationship between self-disclosure and loneliness. PMID- 1405055 TI - [Saccadic eye movement guided by the visual form]. AB - This report describes an experiment in which was measured the onset latency of the saccade to the peripheral target under three conditions of visual cues for the target location. In the central cue condition (the C-condition), the cue was an arrow presented in the central visual field. In the peripheral cue condition (the P-condition), the cue was the form in which the target was presented in the peripheral visual field. In the one-sided cue condition (the O-condition), the cue was the target itself. The saccade latency was measured by means of electro oculography. The results were; (1) the saccade latencies in the three conditions were significantly different from each other, (2) the latency was longest in the C-condition and shortest in the O-condition, (3) the difference in latency between the P and C-conditions was three times as large as that between O and P conditions, (4) the latency variance was significantly larger in the C-condition than in the other conditions, (5) the difference in the variances was not significant between the O and P-conditions. The results were interpreted in terms of (a) cognitive processing of visual form and (b) the characteristics of the saccade system. PMID- 1405056 TI - [Assessment of autonomic function by the spectral analysis of heart rate variability: an examination in a mirror drawing task]. AB - The effect of an experimental task on autonomic function was investigated by spectral analysis of heart rate variability in 13 male college students. Power spectral density of heart rate variability has been said to contain two significant components: respiratory sinus arrhythmia (RSA) as an index of cardiac vagal activity, and Mayer wave related sinus arrhythmia (MWSA) as an index of sympathetic activity with vagal modulation. Those two components were examined during a task of mirror drawing on the CRT. In order to eliminate the effect of respiratory rate on RSA, the respiratory rate was controlled at 15 breaths/min. Furthermore, the coefficient of variance of R-R interval (CV-RR) and the fluctuation of plethysmograph (PTG) were calculated simultaneously. Results indicated that, while RSA decreased significantly, MWSA did not change during the task. On the other hand, neither CV-RR nor PTG showed any significant differences during the task. These findings indicated that cardiac parasympathetic activity was diminished in the mirror drawing task. The significance of spectral analysis of heart rate variability were discussed. PMID- 1405057 TI - [Effect of interrun interval on serial pattern learning in rats]. AB - The effect of interrun interval (IRI) on serial pattern learning was investigated in a runway. One of two serial sequences, a monotonic decreasing sequence (14-7-3 1-0 food pellets) or a nonmonotonic sequence (14-1-3-7-0), was combined factorially with a short (30 s) or a long (30 min) IRI. Following 28 acquisition trials, a short (or long) IRI was transferred to the same sequence with a long (or short) IRI. It was found that anticipation of the O-pellet developed more rapidly in the group receiving a monotonic sequence with a 30 s IRI than that with a 30 min IRI in acquisition phase. The O-pellet was not anticipated by either of the two nonmonotonic groups. Anticipation was eliminated by the increase in IRI, whereas it was developed by the decrease in IRI in the monotonic sequence. These results suggest that time-related factors such as the decay of the memory of numbers of pellets are needed for Capaldi's memory discrimination theory. PMID- 1405058 TI - [An evaluation of the span and direction of spread of the concept "now" (Japanese ima): using both the dual scaling and factor analysis methods]. AB - The purpose of this study was to obtain information about both the span and direction of spread of the concept "now" (Japanese ima) used in short sentences such as "I am--a student." 583 subjects were presented with 55 sentences, and were required first to rate on a 5-point scale the degree of spread of the concept used in each sentence, and then to express its span and direction in terms of seconds, minutes, ... years, decades, or centuries in both a past- and a future-orientation. The latter data were analysed using the Dual Scaling method which revealed three major solutions: "span", "direction", and "interrelation between the previous two". The former data were analysed using the Factor Analysis method which revealed six factors: "moment", "conversion", "limitlessness", "absorption", "limitation" and "hopelessness". Furthermore, second-order analyses were carried out using these six factors, revealing three further factors: "duration", "change" and "timelessness". It was concluded that these latter three factors were identical with the three solutions obtained by Dual Scaling. PMID- 1405059 TI - [Factors related to the maintenance of social interaction among withdrawn preschool children]. AB - It is difficult for withdrawn children to enter a play and to maintain social interaction with other children. This investigation attempted to identify whether the difficulty was due to their incorrect perception of others' responses or due to the lack of their self-confidence. Forty-five 5- and 6-years old nursery school children enrolled in six day-care classrooms served as subjects. They were divided into high middle or low groups by the degree of withdrawal, and each child was asked to play with two other same-age peers. Analyses by the observation of video recordings and the interviewing of the children revealed that the low withdrawals could perceive other children's responses more correctly than any other group, whereas there was no difference among the three groups in self-confidence. Thus, it was interpreted that those highly withdrawal children cannot skillfully enter plays with other children because they were unable to perceive other children's responses correctly. After entering a play, they also remained solitary almost all the time. The highly withdrawn children tended to keep themselves alone, while the children in low and middle degrees of withdrawal seemed to attempt to join other children even after being rejected or neglected by other children. PMID- 1405060 TI - [Influence of affect on everyday memory: self-reference of retrieval cue]. AB - There have been two views as to mood congruent recall: The one interprets it as an automatic process, while the other explains that it appears only when self referent information processing is running. In this study, one experiment was conducted in order to examine these two opposing views. By false feedback of task performance, positive or negative mood had been induced in each subject, who was given two "cue" words, and asked to retrieve everyday events. The result was that mood congruent recall occurred when the word "self" was presented as a cue; but no effect of mood with neutral cues. This result supports the hypothesis that mood congruent recall is found only when self-referent information is processed. However, such effect was not evident in positive mood condition. In positive mood condition, there remains a possibility that mood congruent recall may be an automatic process. The effects of mood on memory were discussed from various viewpoints. PMID- 1405061 TI - [The relationships between sympathetic and parasympathetic tones and cardiovascular responses during active coping]. AB - The relationships between sympathetic and parasympathetic tones and a variety of cardiovascular measures were examined in 27 male college students subjected to an active coping, namely a reaction time task, for five minutes. The results demonstrated an enhanced sympathetic tone during the first one minute (P1), indicating the decreases of pre-ejection period (PEP), left ventricular ejection time, and electromechanical systole (QS2), and the increase of QT/QS2. The reactivities of QT/QS2 and PEP defined by mean changes in the P1 period differed in their relationship with cardiovascular responses in the last four minutes. Although the PEP reactivity was associated with the cardiac performance (stroke volume and PEP/LVET), the QT/QS2 reactivity was correlated with the mean blood pressure (MBP). The reactivities of respiratory sinus arrhythmia (RSA) were defined by the residual difference obtained by subtracting values estimated by baseline RSAs from the mean value of changes during five minutes period. Subjects with high RSA reactivity (vagal withdrawal) showed higher heart rate and MBP than those with low RSA reactivity. The results are discussed with respect to the cardiac loading factors and hemodynamics. PMID- 1405062 TI - [Dyspnea and respiratory reflexes]. AB - It has been suggested that afferents from intercostal muscles may play a role in the genesis of dyspnea. In this study, lower intercostal muscles were tapped or vibrated to induce a reflex, evoked potentials, and sensation. The tapping stimulus induced H reflex in the same muscle with a latency of 12 msec. Also the same stimulus induced evoked potentials in the cerebral cortex (N1: 19.8 +/- 1.2 msec). This suggests projection of the intercostal muscle spindle afferents to the cerebral cortex. 100 Hz vibration induced a later component, presumably an event-related potential, at 250 msec after the onset of both the inspiratory and expiratory phase. Thus, it may be possible that intercostal muscle spindle afferents project to the cerebral cortex and play a role in respiratory sensation. It has been suggested that dyspnea is reduced by increasing inspiratory and expiratory intercostal muscle spindle afferents during the inspiratory and expiratory phases, respectively. Thus, stretching the inspiratory and expiratory intercostal muscles during the respective muscular contraction phase may be effective in reducing dyspnea. PMID- 1405063 TI - [Dyspnea sensation and chemical control of breathing]. AB - In order to estimate the role of peripheral chemosensitivity in dyspnea sensation, we performed BH experiment under the acute or chronic hypoxic condition. The former was simulated by a given rate (0-3.2 mg/kg/hr) of doxapram infusion. The latter experiment was carried out during sojourn in Lhasa (3700 m), China. Subjects conducted BH by inhaling 7% CO2 in O2 and assessed dyspnea sensation by visual analog scale (VAS) while repeatedly measuring PCO2 at breaking point (BP). Lowering of resting PETCO2 by augmented ventilation was derived by doxapram infusion and during acclimatization at high altitude. The effect of PCO2 on VAS was enhanced by doxapram. However, altitude acclimatization resulted in attenuated effect of PCO2 on VAS despite of further development of hypocapnia. The rate of PCO2 elevation during doxapram infusion was reduced and it might be attributed to decreased body storage of CO2. On the other hand, its rate was tended to recover to sea level value after acclimatization at high altitude and it may have cancelled the mitigated dyspnea sensation. Thus, BHT almost comparable period in both acute hypoxia and during altitude acclimatization. These results suggest that CO2 storage in the body contributes to modify dyspnea sensation as well as augmented peripheral chemosensitivity. PMID- 1405064 TI - [Dyspnea and behavioral control]. AB - Respiration is automatically regulated via chemo- and mechanoreceptors existing in and outside the lungs, but it is also controlled voluntarily by behavioral factors. Voluntary increase in ventilation accentuates dyspnea and the sensory intensity at a given ventilation does not differ from that of exercise-induced hyperventilation, but it is significantly smaller than that during hypercapnia or hypoxia. Voluntary constraint of ventilation augments dyspnea in proportion to the degree of constraint even under isocapnic hyperoxia, and the respiratory sensation during constrained breathing is qualitatively more discomfortable than that during hyperventilation. Changes in the level and pattern of breathing under constant levels of chemical stimuli increase respiratory sensations and the intensity of dyspnea is minimal near the spontaneous levels, which supports the hypothesis that breathing is behaviorally regulated in part to minimize dyspnea. The system of behavioral control of breathing appears to be involved in the maintenance of body homeostasis by modifying the respiratory output through respiratory sensations. PMID- 1405065 TI - [Dyspnea sensation during resistive loading]. AB - To examine the relationship among the sensation of dyspnea, the respiratory muscle oxygen consumption (VO2 resp), minute ventilation and occlusion pressure, seven normal volunteers were studied during incremental dead space loading induced hyperventilation with and without inspiratory resistive load. Although the sensation of dyspnea and VO2 resp at the same level of minute ventilation increased with an increase in resistance, there appeared to be a unique relationship among the sensation of dyspnea, VO2 resp and occlusion pressure, which was not affected by inspiratory resistive loading from 0 to 20 cmH2O/l/sec. These results show that the ventilatory command signal is closely related to the dyspnea sensation. We also found that during incremental dead space loading the quality of the sensation changed relatively quickly at some point, where tidal volume was maximum with each resistive loading and the breathing pattern changed. In the other experiment, the functional residual capacity (FRC) decreased during inspiratory resistive and elastic loading. Because the decreased FRC was associated with the decrease in the dyspnea sensation, it was speculated that the subject decreased his FRC through a cortical response so that the sensation of dyspnea during loading decreased. PMID- 1405066 TI - [Relationship of respiratory muscle fatigue and respiratory effort sensation: mechanisms and treatment]. AB - We investigated whether fatigue of the expiratory muscle may account for a change in the respiratory effort sensation in normal subjects. We also examined the effects of inspiratory muscle training (IMT) and a beta 2-agonist, fenoterol, on respiratory effort sensation during loaded breathing. Experiment 1: Expiratory threshold loading was performed until exhaustion or 30 min, to induce expiratory muscle fatigue. The respiratory effort sensation was scored using a modified Borg scale. The maximum static expiratory pressure during loading (PEmaxload) decreased with time, and the Borg score rose with time. The relationship between the sensory score and PEmaxload was virtually linear. Experiment 2: Twice daily, IMT was performed using a pressure threshold device for 15 min in each session. The inspiratory threshold was set to 30% of each subject's maximum inspiratory pressure (Plmax) and IMT was continued for 4 weeks. Respiratory sensation (Borg score) was evaluated during a progressive exercise test. IMT increased inspiratory muscle pressure by 30%. However, there was no change in Borg score during the exercise test. Experiment 3: Fenoterol (5 mg) was given 2 hours before the inspiratory threshold loading, and then threshold loaded breathing was continued until exhaustion or 60 min. Endurance time increased by 50% in fenoterol group compared to placebo group. The increase in Borg score with time was less in fenoterol group than in placebo group. The decrease in respiratory muscle strength after loading was comparable in both groups. We conclude that the increased respiratory effort sensation during expiratory threshold loading is closely related to expiratory muscle fatigue as indicated by the decrease in expiratory muscle force.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405067 TI - [Relationship between anaerobic threshold and breathlessness during exercise]. AB - We studied the possibility that during incremental exercise anaerobic threshold (AT) is associated with an increase in breathlessness in subjects with increased impedance or respiratory system. Six patients with chronic lung diseases (CLD) and six healthy subjects performed cycle ergometer exercise under two conditions; with free resistive loading and with 9 cmH2O/l/sec of inspiratory resistive loading (IRL). Ventilation, respiratory pattern, VO2, VCO2, were measured every 15 sec by a metabolic cart, Minato Respiromonitor RM 300. AT was determined by V slope method. Mouth occlusion pressure (P0.1) was also measured in six subjects during exercise. The subjects selected a number of modified Borg scale (psi) to express their breathlessness during exercise by pushing a electrically potentiated remote button. Slopes of changes in psi with increasing work-load, delta psi/delta watt-slope, were calculated before and after V-slope AT, and each inflection point of VE, respiratory rate, VT/Ti, and VCO2. In order to evaluate which parameters are the most responsible for a change in psi, statistical significance (P-value) in changes of slope of each parameters were compared. The delta psi-slope increased with the highest significance after AT point. Under IRL the significance was more pronounced. There was a highly significant linear correlation between P0.1 and psi during exercise both under free resistive loading and IRL. In addition the increase of P0.1 with incremental exercise was characterized by a presence of inflection at a workload of V-slope AT in most of the subjects. From these results it was concluded that anaerobic threshold was closely associated with an increase of breathlessness during exercise via enhancing respiratory motor command.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405068 TI - [Relation between dyspnea and personality in patients with pulmonary emphysema and healthy subjects]. AB - To determine whether personality is related to dyspnea sensation, 19 healthy males and 17 male patients with pulmonary emphysema were tested for modified visual analog scale (VAS) during hypoxic and hypercapnic interventions. Personality was tested by both Yatabe-Guillford test and manifest anxiety scale. VAS score correlated positively with anxiety score during hypercapnia and inspiratory resistive loading under hypercapnia in healthy subjects. In patients, anxiety score correlated positively with VAS scores during hypoxia, hypercapnia, and resistive loading under hypercapnia. Scores for nervousness and cyclic tendency correlated with VAS scores during hypoxia and hypercapnia in patients. These results indicate close relation between anxiety and dyspnea in healthy as well as emphysematous subjects. In emphysema, nervousness and cyclic tendency are the additional determinants for dyspnea. PMID- 1405069 TI - [Dyspnea and rib cage distortion in postural changes]. AB - We studied the topographical ventilatory motion and electrical muscle activity (EMG) of intercostal muscle within the rib cage for the patients complaining dyspnea produced mostly by their postural changes. There were inappropriateness between the rib cage motion and EMG and this inappropriateness was closely related to a sensation of dyspnea. We could relieve partly dyspnea by applying the negative pressure ventilator, because of prevention of a distortion of rib cage. Based on these clinical observation, we concluded that one of mechanism to sense dyspnea was the inappropriateness between motion and electrical muscle activity within the rib cage. PMID- 1405070 TI - [A study of chest X-ray classification of farmer's lung--correlation between X ray pattern and background factors]. AB - Patients with farmer's lung were classified into five groups according to their chest X-ray pattern, and the background of each group was studied with respect to stage, severity, and prognosis. Type I group, which has fine nodular shadows on chest X-ray, showed a significantly high percentage of lymphocytes in BAL cells (p less than 0.01). Type V group, which has irregular patchy shadows on chest X ray, showed increased peripheral WBC counts, increased CRP score, and decreased PaO2 compared to the other groups. Type II, III, and IV groups, which are characterized by combined X-ray patterns such as nodular shadows, ring-like shadows, and irregular pulmonary markings, had no specific background features according to our study. Our results suggest that type I and type V groups are likely to represent acute phase and severe phase, respectively. We could not identify any significant factors indicative of chronic disease in terms of restrictive and diffusion impairment of pulmonary function tests and pathologic findings obtained by TBLB. The chest X-ray classification we proposed is useful for the diagnosis of the acute and severe stages of farmer's lung. PMID- 1405071 TI - [Relationship between clinical symptoms and nocturnal oxygen desaturation in sleep apnea syndrome and chronic lung disease]. AB - Nocturnal oxygen desaturation (NOD) is commonly seen not only in sleep apnea syndrome (SAS) but also in chronic lung disease (CLD) including chronic obstructive lung disease even without sleep apnea. However, the relationship of NOD to clinical symptoms such as morning headache, sleep deprivation due to breathlessness, and daytime sleepiness is not known. In this study, we examined by polysomnography the relationship between several NOD indexes, parameters of apnea, and subjective symptoms in 25 patients with SAS and 22 patients with CLD. In addition, the relation between daytime arterial blood gas data and NOD indexes, parameters of apnea, was examined. In the SAS group, there were no differences in any parameters of NOD and apnea between patients with subjective symptoms and those without symptoms. However, in the CLD group, symptomatic patients had significantly lower lowest SaO2, higher mean SaO2, and longer total desaturation time. In both groups, daytime PaCO2 had a significant correlation with several NOD parameters such as mean SaO2, lowest SaO2, and total desaturation time. In the SAS group, daytime PaCO2 was also correlated with the parameters of apnea. On the other hand, daytime PaO2 was significantly correlated with mean SaO2 only in the CLD group. From these data, we conclude that in patients with SAS, daytime PaCO2 is a variable that is related to the degree of NOD, and that in patients with CLD, subjective symptoms and daytime PaO2 in addition to daytime PaCO2 are associated with NOD. PMID- 1405072 TI - [Probucol inhibits tobacco smoke-induced decrease in plasma anti-elastase activity and ferroxidase activity in rats]. AB - Elastolytic enzymes and active oxygen species derived from leukocytes and alveolar macrophages during exposure to tobacco smoke, together with active oxygen species directly derived from tobacco smoke, are thought to play a crucial role in the pathogenesis of pulmonary emphysema by inactivating alpha 1 protease inhibitor (alpha 1 PI), a novel anti-elastase. We studied the inhibitory effect of probucol, an oral hypocholesterolemic agent, on tobacco smoke-induced decrease in plasma anti-elastase activity (EIA) and ferroxidase activity (FA) in conscious venous catheter instrumented rats. Rats exposed to the smoke of 5 cigarettes (nicotine 11 mg, tar 115 mg) in a plastic chamber showed a prompt increase in plasma COHb to 17.9 +/- 2.7%, and a prompt decrease in plasma EIA by -17.9% (p less than 0.05) and FA by -14.8% (p less than 0.01), which lasted for 6 hours after exposure. Rats administered probucol (1% probucol in food) for 3 days showed normal cholesterol plasma levels, and rats administered probucol for 4 weeks showed hypocholesterolemic plasma levels. EIA and FA were not depressed after smoking, and lipid peroxide product (TBA reactive substance) in lung tissue (p less than 0.05) and serum (p less than 0.1) showed a smaller increase in association with a smaller decrease in the ratio of lung tissue GSH/GSSG (p less than 0.01) compared with control rats. These results indicate that probucol, via its antioxidant action rather than its cholesterol lowering effect, has a protective effect on lung exposed to tobacco smoke in terms of protease antiprotease balance and oxidant-antioxidant balance. PMID- 1405073 TI - [Manipulation, premedication, and chemoprophylaxis for fiberoptic bronchoscopy]. AB - Manipulation, premedication, and chemoprophylaxis for fiberoptic bronchoscopy vary among institutions. We analyzed the actual conditions by means of a questionnaire distributed to 29 institutions. With regard to premedication, a combination of atropine sulfate and sedatives, such as hydroxyzine hydrochloride, was the most common method. In cases with heart disease and elderly subjects, a lower dosage or omission of atropine was common. In cases with marked anxiety, narcotics were prescribed. Bronchofiberscopic examination was performed under local anesthesia at all institutions. Lidocaine 4% was used for anesthesia of the orolarynx, and 2% was used for the tracheobronchus. For prophylaxis of infection, 19 of 29 institutions prescribed antibiotics routinely or under certain circumstances. ECG was used in 14 institutions, and percutaneous oxygen monitoring in 5 institutions. It is concluded that the manipulation and premedication for fiberoptic bronchoscopy vary between institutions. It is necessary to determine more efficacious and safer methods for fiberoptic bronchoscopy. PMID- 1405074 TI - [Malignancies in patients with sarcoidosis]. AB - We evaluated the occurrence and type of malignant tumors in 148 patients with sarcoidosis followed at the Okayama University Hospital. Nine patients had malignancies; in 2 of 9 patients the development of malignancy preceded that of sarcoidosis, and one patient presented with sarcoidosis and malignancy at the same time. Six patients developed six types of malignancy following the development sarcoidosis; one case each of stomach cancer, lung cancer, breast cancer, thyroid cancer, testicular tumor, laryngeal cancer, and chronic lymphocytic leukemia. There was no significant difference between sexes (3 males and 3 females). The mean age of the cancer group at the onset of sarcoidosis was 56 years, which was significantly higher (p less than 0.05) than that of the control group. In these 6 patients, the mean interval from onset of sarcoidosis to detection of cancer was 11.7 years (range 1.5 to 30.2 years). The relative risk of malignancy was calculated based on the data for 148 patients with sarcoidosis with a total of 1371 person-years. The expected incidences of cancer for all sites and specific sites were estimated by applying age- and sex-adjusted person-years. The observed incidence of cancer was significantly (p less than 0.05) greater than the expected incidence for thyroid cancer, laryngeal cancer, and leukemia. No significant difference in incidence was found for all sites or for the other sites of cancer. The increased cancer incidence in sarcoidosis may be secondary to immunological abnormalities associated with this disease. PMID- 1405075 TI - [Long-term effects and complications of home nasal CPAP therapy for obstructive sleep apnea patients]. AB - We treated 23 patients with obstructive sleep apnea syndrome (OSAS) by nasal continuous positive airway pressure (NCPAP) at home, and examined the long-term compliance, clinical effects, and complications after NCPAP therapy. Nineteen patients continued and four patients discontinued the therapy during the mean observation period of 15 months, and the compliance was 83%. There was no significant difference in age, weight, and sleep data between the compliant group (C) and non-compliant group (NC). The causes of discontinuation of therapy were lack of adaptation to the apparatus (2 cases), improvement of clinical symptoms due to weight reduction (1 case), and induction of asthma attack (1 case). Disappearance of excessive daytime sleepiness, improvement of sleep quality, and disappearance of nocturia were observed in most cases, and disappearance of morning headache and improvement of sexual ability and emotional instability were also observed in several cases. Nine cases (39%) complained of discomfort due to the nasal mask and 6 cases (26%) complained of dryness of the mouth and nose, whereas 10 cases (43%) experienced no adverse effects. No serious complications were observed. These findings suggest that long-term home NCPAP is an effective and safe treatment for OSAS patients. PMID- 1405076 TI - [Endoscopic endobronchial metastasis]. AB - Although the incidence of endobronchial metastasis in cases of extrathoracic tumors is 2 to 5 percent in autopsy reports, it is about 30 percent according to endoscopic examination (so-called endoscopic endobronchial metastasis). To confirm the nature of endoscopic endobronchial metastasis, we reviewed the records from 1980 to 1990, presuming the primary foci of metastasis. Of the 36 patients with metastatic pulmonary tumor, 6 (16.7%) were diagnosed as having endobronchial metastasis endoscopically. The primary tumors were colonic cancer (2), prostatic cancer (2), cancer of the tongue (1), and renal cell carcinoma (1). The chest X-ray findings were nodular shadow (3), atelectasis (2), and hilar lymphadenopathy with atelectasis (1). Three patients were treated by lobectomy and the others by systemic therapy alone. The presumed primary foci of metastasis were peripheral lung (3), mediastinal lymph node (1), and undetermined (2). The results of the present study suggest that so-called endoscopic endobronchial metastasis does not necessarily imply metastasis to the bronchial wall. PMID- 1405077 TI - [Bronchoalveolar lavage fluid findings in rheumatoid arthritis]. AB - Findings of bronchoalveolar lavage fluid (BALF) were compared among three groups of patients: rheumatoid arthritis (RA) with or without interstitial lung disease (ILD), and collagen disease other than RA accompanied by ILD. Regardless of the presence or absence of associated ILD, the RA groups showed higher numbers of neutrophils in BALF with a mean number about 10 times that of the collagen disease group. In contrast, the percentages of lymphocytes in the RA groups were lower than that in the collagen disease group. Classification of alveolitis on the basis of BALF findings revealed neutrophil type (N) in 55% of the RA patients and lymphocyte type (L) in 25%. In the collagen disease group, N was found in 15.4%, and L in 38.5%. Regarding the lymphocyte subsets, many patients with RA accompanied by ILD had a CD 4/8 ratio of 1 or great. These findings suggest that highly characteristic neutrophil alveolitis is present in the pulmonary interstitium from the initial stage of RA. PMID- 1405078 TI - [Percent home stay, an index for the clinical evaluation of home oxygen therapy]. AB - To evaluate the usefulness of % home stay as an index for evaluation of the clinical effects of long term home oxygen therapy (HOT), we retrospectively examined 70 consecutive cases with chronic respiratory failure treated by HOT in the Ogaki area. The clinical data, underlying diseases, and survival rate of the cases were similar to recent official statistics in Japan; thus, we considered these cases to be a representative population. For evaluation, we tentatively used a % home stay of 70% as the standard level, which was determined by the 25th percentile line. To examine the usefulness of this standard, we classified the study population into 2 groups (the group with % home stay of greater than 70% (Group A, n = 54), and the group with % home stay of less than 70% (Group B, n = 16)), and compared the outcomes, survival rates, life situations, and background factors between these groups. As a result, there were significant differences in outcome (at home 34%, hospitalized 11%, and dead 22% in group A, and 6%, 44%, and 50%, respectively in group B, p less than 0.05), survival rate (p less than 0.05 by logrank test), and life situation between these groups. Thus, a % home stay of 70% is thought to be a useful standard for clinical evaluation, because it reflects both the prognosis and quality of life of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405079 TI - [A study of epithelioid cell granulomas in transbronchial lung biopsy specimens of sarcoidosis patients--correlation between granulomas and clinical activity or chest X-ray lesions]. AB - The 565 pulmonary tissue specimens taken from 155 sarcoidosis patients by transbronchial lung biopsy (TBLB) were studied by light microscopy. Particular attention was paid to the mean number and type of epithelioid cell granulomas, the mean number of giant cells, and the degree of lymphocyte cuffing, perigranulomal fibrosis, and granuloma confluence. The granulomas were divided into three types, hypertrophic, atrophic, and hyalinofibrous. In stage II and III patients, the mean number of granulomas and giant cells, the positive rate of hyalinofibrous granuloma, the relative proportion of the hyalinofibrous granuloma group, and the degree of fibrosis and confluence were significantly higher than those in stage O and I patients. The mean number of granulomas was related to the serum level of angiotensin converting enzyme and 67Ga uptake into lung parenchyma, but not to the cellular findings of bronchoalveolar lavage fluid (BALF). The lymphocyte count of BALF in the hypertrophic granuloma group was significantly higher than that in the atrophic and hyalinofibrous granuloma groups. CD4/CD8 ratio of lymphocytes in BALF was significantly lower in the hyalinofibrous granuloma group than in the other groups. In stage I patients, the resolution of intrathoracic lesions on chest X-ray was significantly more frequent in the atrophic granuloma group than in the hypertrophic granuloma group, 2 and 5 years after TBLB was performed. The pulmonary lesions had a tendency to persist for a long time in stage II and III patients with hyalinofibrous granuloma or granuloma confluence. Newly appearing pulmonary lesions showed hypertrophic granulomas as well as marked lymphocyte cuffing. PMID- 1405080 TI - [A case of obstructive sleep apnea syndrome with increased lung water content during sleep]. AB - A 57-year-old man was admitted complaining of sleep disturbance. All night polysomnography showed a pattern of obstructive sleep apnea. We performed 201Tl scintigraphy to evaluate hemodynamic change and degree of stress on the right ventricle during sleep, and compared it with a 201Tl scintigram during wakefulness. We recognized 201Tl uptake by the lung in the 201Tl scintigram during sleep, but not during wakefulness. To determine the mechanism of 201Tl uptake by the lung during sleep, we measured lung water content during sleep by double indicator dilution method (Nihon Koden, NTV-1100). We recognized an increase of lung water content during sleep. We consider that the increase of lung water content during sleep is caused by sleep apnea, probably by hemodynamic change due to negative pleural pressure swings during sleep apnea. PMID- 1405081 TI - [A case of flomoxef-induced pneumonitis]. AB - We report a case of flomoxef-induced pneumonitis. A 22-year-old man was treated with flomoxef following liver biopsy. A few days later he developed a high fever and severe dyspnea, and his chest X-ray film revealed diffuse reticulo-nodular shadows in both lung fields. We suspected interstitial pneumonitis due to flomoxef, and pulse therapy with methylprednisolone was started. He showed rapid recovery of symptoms and marked regression of pulmonary infiltration in his chest X-ray. Lymphocyte stimulation test was positive to flomoxef, which was compatible with the diagnosis of drug-induced pneumonitis. To our knowledge, there has been no previous case of pulmonary hypersensitivity to flomoxef reported in Japan. PMID- 1405082 TI - [An autopsy case of sarcoidosis associated with renal failure]. AB - A 62-year-old woman presented with uveitis and abnormal chest X-ray (bilateral hilar adenopathy). Skin biopsy in 1983 had revealed non-caseating epithelioid cell granuloma consistent with sarcoidosis. Her serum biochemical investigations and exploratory laparoscopy suggested nodular liver cirrhosis, but biopsy was not performed. Both blood urea nitrogen (BUN) and serum creatinine values were within normal limits. She received prednisolone therapy of 15 mg daily initially, and later a maintenance dose of 5 mg daily. In 1985, she complained of skin itching and her laboratory data revealed severe renal insufficiency (BUN 97 mg/dl, serum creatinine 12.2 mg/dl) and hypercalcemia (corrected serum calcium level: 11.5 mg/dl). Prednisolone treatment (40 mg daily) resulted in a dramatic improvement of renal function as well as other clinical abnormalities due to sarcoidosis, without any significant changes in liver function. She died of cerebral infarction in 1989. Autopsy showed interstitial nephritis with tubular calcinosis and hyalinized glomeruli. It is postulated that hypercalcemia due to sarcoidosis contributed to the renal failure in this patient. This case suggests that renal damage due to sarcoidosis may be reversible with appropriate corticosteroid therapy. PMID- 1405083 TI - [A case of aspirin-induced asthma due to ketoprofen adhesive agent]. AB - A 40-year-old woman who had been diagnosed as having aspirin-induced asthma was admitted with stridor. She had a history of surgery for sinusitis and nasal polyps, and severe asthmatic attack requiring mechanical ventilation after administration of puranoprofen (Niflan). On the second day of hospitalization, she used a ketoprofen adhesive agent (Miltax, 30 mg) for a stiff shoulder. Stridor developed five hours later, progressing to a severe asthmatic attack with loss of consciousness, requiring mechanical ventilation. The serum level of ketoprofen was very high (81.7 ng/ml); therefore, provocation challenge test was performed to confirm the possible relationship between the ketoprofen adhesive agent and asthmatic attack. After closed patching of the agent (15 mg) on her lower leg, stridor developed, and FEV1.0 and PFR decreased, in association with an increase of the serum level of ketoprofen to a maximum of 38.0 ng/ml. These results show that the topical application of a ketoprofen adhesive agent induced the asthmatic attack by transdermal absorption in this patient. PMID- 1405084 TI - [A case of foreign body granuloma due to aspiration of a twig of Cryptomeria]. AB - A 65-year-old man was admitted to Oita Medical School Hospital with complaints of hemoptysis and left anterior chest pain. Chest X-ray film showed a nodular shadow, about 1 cm in diameter, in the left S8 area. A specimen obtained by transbronchial biopsy showed no malignant findings. However, left lower lobectomy was performed because of the possibility of malignancy. The resected specimen contained a twig of cryptomeria within dark-red lung tissue. Histologically, the foreign body granuloma was surrounding a vegetable fiber. We had no information of an episode of pruning a cryptomeria and aspiration of a twig before the operation. Cryptomeria is an extremely rare bronchopulmonary foreign body, and the present case suggests that bronchopulmonary foreign body granuloma is an important disease in the differential diagnosis of pulmonary nodules. PMID- 1405085 TI - [A case of pulmonary infiltration with eosinophilia (PIE) syndrome induced by Saiboku-To (TJ96). Detection of ECF activity in lymphocytes stimulated with TJ96]. AB - A case of PIE syndrome induced by Saiboku-To (TJ96) is reported. A 56-year-old woman had been treated for intractable bronchial asthma since the age of 42 years. She had a history of PIE syndrome induced by disodium cromoglycate 4 years previously (Jpn. J. Thoracic Disease, 27.1.1989). To reduce the dose of prednisolone for her asthma, administration of TJ96 was started in Dec. 1989. After 5 months of TJ96 treatment, she developed dry cough, fever, and chest pain. Physical findings and laboratory examinations revealed pulmonary infiltrations in the right lung field and severe eosinophilia. Because of suspected drug-induced PIE, TJ96 was stopped and 30 mg/day prednisolone was administered. Her symptoms and laboratory abnormalities subsequently resolved. To confirm the diagnosis of drug-induced PIE syndrome, drug-induced lymphocyte stimulation tests with TJ96 and other drugs were performed. TJ96 significantly induced lymphocyte blastogenesis with a stimulation index of 6.1. Moreover, the supernatant of the incubation mixture of TJ96 and peripheral lymphocytes from the patient showed marked eosinophil chemotactic activity. To our knowledge, there has been no previous report of PIE syndrome induced by TJ96. In addition, this is the first report of the detection of ECF activity in lymphocytes induced by an offending drug in vitro. PMID- 1405086 TI - [Three cases of surgical treatment of dumbbell neurogenic tumor of the mediastinum--evaluation of intraspinal extension in cases without clinical symptoms]. AB - Three cases of dumbbell neurogenic tumor of the posterior mediastinum are reported. None of these cases had any clinical symptoms, and an abnormal mass shadow of the mediastinum had been detected on routine chest roentgenogram. In these three cases, however, myelogram and/or CT findings were suggestive of tumor extension to the spinal canal in various degrees. Two tumors were resected in two stage operations with combined thoracic and neurosurgical approaches, and the other case was treated by one-stage operation with the combined two approaches. All tumors were completely resectable without serious complications such as hemorrhage, leakage of spinal fluid, or neurologic deficit. Even in asymptomatic patients with neurogenic tumor located in the paravertebral region, it should be determined whether or not the tumor extends to the spinal canal through the intervertebral foramen, prior to planning the surgical procedure. PMID- 1405087 TI - [A case of endobronchial fibroma associated with recurrent pneumonia]. AB - We present a case of endobronchial fibroma in a 59-year-old man admitted for repeated pneumonia, successfully treated by endoscopic Nd-YAG laser. His chest X ray showed an infiltrative shadow in the right lower lung field and a mass shadow within the truncus intermedius. Bronchoscopy revealed a polypoid mass with lobulated whitish surface, obstructing 90% of the lumen. A biopsy taken from the tumor was suggestive of fibroma histologically. Two previous case reports stated that endobronchial fibroma readily detaches from the bronchial wall during removal. The tumor was successfully removed without dropping any tumor fragment to obstruct the distal bronchus by means of biopsy forceps manually attached to an endoscope with endoscopic Nd-YAG laser. The resected tumor was mainly composed of collagen fibers with scanty spindle-shaped fibroblastic cells, which was considered consistent with endobronchial fibroma. Endobronchial fibroma is a rare benign lung tumor, and only seven cases have been reported in the Japanese literature. There was no recurrence at three years and nine months. PMID- 1405088 TI - [A case of systemic arterial supply to normal lung without sequestrated lung]. AB - A 19-year-old man was admitted to our hospital because of bloody sputum. His chest radiograph showed funicular shadows adjacent to the descending aorta in the left lower lobe and absence of vascular structures in the lower portion of the left hilum. His chest CT showed increased vascularity and slightly increased parenchymal density in the left basal segments. No cystic lesions were observed on CT. Angiographic examinations revealed that the left basal segments were supplied by an aberrant artery arising from the thoracic aorta, instead of the pulmonary artery. Left lower lobectomy was performed. Gross findings at surgery and histological examination confirmed the diagnosis of systemic arterial supply to normal lung without sequestrated lung. The main histological findings of the specimen were hemorrhage in alveolar spaces and dilatation of vessels. These findings seemed to correspond to the CT findings. We consider that CT is useful for the diagnosis of this disease. PMID- 1405089 TI - [A case of sarcoidosis presenting with Heerfordt's syndrome, associated with hepatosplenomegaly, pleural effusion, and ascites]. AB - A 30-year-old female developed symptoms consistent with Heerfordt's syndrome (complete type) and was effectively treated with steroid. However, she developed hepatosplenomegaly, bloody pleural effusion, and ascites one year after discontinuation of steroid therapy. The symptoms were considered to be due to sarcoidosis since serum ACE level, and ACE level and OKT4/8 ratio in pleural and peritoneal effusions were significantly elevated, and readministration of steroid normalized these changes. Bloody pleural and peritoneal effusions are very rare complications of sarcoidosis. PMID- 1405090 TI - [A case of systemic lupus erythematosus associated with Sjogren's syndrome diagnosed by lung localization]. AB - A 30-year-old female, diagnosed as having SLE and followed at our hospital while receiving oral prednisolone (5 mg/day) for about 6 months, was admitted because of fever and productive cough. Chest X-ray and CT scan showed a tumor-like homogeneous shadow in the right middle lobe. Antibiotic treatment was not effective. Specimens obtained by TBLB revealed massive infiltration of mature plasma cells and lymphocytes into the alveolar septa and interstitial tissues. These findings were considered compatible with lymphoid interstitial pneumonia. Associated conditions such as Sjogren's syndrome were suggested, but the diagnostic criteria of Sjogren's syndrome were not satisfied. Both the abnormal shadow on chest X-ray and the clinical symptoms markedly improved by increasing the dose of prednisolone (20 mg/day). After 3 months, however, bilateral BAL findings showed alveolar lymphocytosis, providing evidence that subclinical diffuse pulmonary involvement had continued. This case indicates that radiological appearance may vary depending on the extent of lung involvement, even if the histological features are identical. It is concluded that the present diagnostic criteria of Sjogren's syndrome must be reconsidered so as not to overlook subclinical and asymptomatic cases of Sjogren's syndrome. PMID- 1405091 TI - [A case of bucillamine-induced pneumonitis]. AB - A 65-year-old woman with rheumatoid arthritis was treated with gold (gold sodium thiomalate), bucillamine, and other drugs. Gold was discontinued because of rash. Consequently she presented with high fever and alopecia, and was admitted with dyspnea. Chest X-ray showed diffuse bilateral reticulolinear infiltrates. The percentage of lymphocytes was increased and OKT4/8 ratio was decreased to 0.22 in bronchoalveolar lavage fluid (BALF). In lung tissue specimens obtained by TBLB, alveolitis with Masson's bodies was seen on light microscopy, and electron micrography showed interstitial edema with desquamated macrophages in the alveolar space and lipid-laden pericytes, secondary to extensive destruction of the alveolar-capillary barrier. After discontinuation of drugs, her symptoms and infiltrates on the chest X-ray resolved. Furthermore, the results of drug lymphocyte stimulation test (DLST) were positive for both drugs. We diagnosed this case as bucillamine-induced pneumonitis, since the symptoms developed after the administration of bucillamine; however, an interaction between bucillamine and gold may have contributed to the occurrence. PMID- 1405092 TI - [A case of chronic interstitial pneumonia with benign monoclonal gammopathy (IgM k) and thrombocytopenia]. AB - A 53-year-old woman was admitted on 13th October 1988 with symptoms of dry cough and shortness of breath persisting for 1 year. On physical examination, fine crackles were audible over her back. Chest X-ray showed bilateral reticulonodular shadows and collapse of the bilateral lower lobes. Chest CT showed patchy areas of increased density distributed predominantly in the subpleural zone. Laboratory data on admission showed thrombocytopenia, hypergammopathy (IgG, 2044 mg/dl; IgA, 286 mg/dl; IgM, 1645 mg/dl), and positive ANF. Further examinations demonstrated that anti-platelet and anti-centromere antibodies were positive in the serum, and the titer of PA-IgG was high (56 ng/10(7) platelets). Histopathological examination of the open lung biopsy demonstrated honeycombing and thickening of the alveolar walls, with slight infiltration of chronic inflammatory cells. These histopathological findings were comparable with usual interstitial pneumonia. We report a very rare case of chronic interstitial pneumonia complicated by benign monoclonal gammopathy and thrombocytopenia. Although it remains unclear, these abnormalities may have been caused by immunological mechanisms. PMID- 1405094 TI - [A case of sarcoidosis with primary acute pulmonary cavitation]. AB - A 23-year-old man was admitted to our hospital on June 24, 1991, because of worsening chest X-ray findings of sarcoidosis. In August 1990, he was referred to our outpatient office, because of BHL and nodular lesions on chest X-ray film performed at his company 4 months earlier. At that time, serum ACE was elevated to 34.0 IU/l, and Ga scintigraphy showed abnormal uptake in bilateral lacrimal and salivary glands, mediastinal and hilar lymph nodes, and in the lung fields. TBLB specimen showed noncaseating epithelioid granuloma with giant cells and negative stains for acid-fast bacilli. Although it was planned to follow this patient without medication, he did not return to our outpatient department. In June 1991, because of worsening of lesions in the lung at annual checkup at his company, he was referred and admitted for steroid therapy. Chest X-ray film on admission showed BHL, multiple nodular lesions in both lung fields, and bullous change in the left upper lobe. Chest CT on admission showed three cavitating lesions within preexisting nodules. PPD skin test was negative, and sputum smears and cultures were repeatedly negative for pyogenic bacteria and acid-fast bacilli. Therapy was initiated with prednisolone 30 mg daily. Four months later, there was marked resolution of BHL and nodular lesions, and the cavitating lesions were no longer visible on chest X-ray film. From the clinical and radiological observations, it is concluded that the cavitating lesions in the present case were primary acute pulmonary cavitation in sarcoidosis, distinct from infection, bullae, or cystic bronchiectasis which are seen in the chronic and fibrotic stages of sarcoidosis. PMID- 1405093 TI - [A case of pulmonary sarcoidosis with B lymphocytosis in peripheral blood]. AB - A 24-year-old man was admitted on October 14, 1988, with bilateral cotton-like shadows on chest X-ray film. Chest CT demonstrated multiple nodular shadows in bilateral lung fields. Laboratory data on admission showed peripheral blood lymphocytosis and slight decrease of serum IgG and IgA. ACE was within normal limits, and BALF findings showed no increase of lymphocytes. Surface marker analysis of peripheral blood lymphocytes showed an increase of B lymphocytes of antibody independent stage (B1, B4, J5, OKB7, sIgM, and sIgD positive cells were increased). Southern blot analysis of peripheral blood showed no rearrangement of immunoglobulin chains (H chain and L chain). In order to differentiate sarcoidosis from lymphoproliferative disorder, open lung biopsy was performed. Pathologic study revealed multiple epithelial granulomas without caseation. Immunohistochemical study demonstrated no accumulation of B cells of the lung. This patient was pathologically diagnosed as having pulmonary sarcoidosis. The abnormal chest shadows gradually improved without therapy; however, B cell lymphocytosis and slight decrease of serum IgG and IgA persisted. In general, lymphocytopenia of peripheral blood is usual in sarcoidosis. We report a rare case of pulmonary sarcoidosis with polyclonal B lymphocytosis of antibody independent stage in peripheral blood. PMID- 1405095 TI - [Effects of inhaled and intravenous furosemide on bronchial hyperresponsiveness in patients with chronic congestive heart failure]. AB - We studied the effects of inhaled and intravenous furosemide (40 mg) on bronchial responsiveness to acetylcholine (ACh) in patients with chronic congestive heart failure. The measurement of bronchial responsiveness was performed by inhaling doses of ACh and calculating the provocative concentration of ACh needed to cause a 20% fall in FEV1.0 (PC20-ACh). Intravenous furosemide (N = 11) had a marked diuretic effect (urine output 1014 ml (SEM 156) in 2 hours), but had no effect on resting pulmonary function and PC20-ACh. In contrast, inhaled furosemide (N = 10) had no effect on urine output and resting pulmonary function, but caused significant increase in PC20-ACh from 2.74 (GSEM 1.28) to 8.47 (GSEM 1.22) mg/ml (p less than 0.05). We conclude that inhaled furosemide, but not intravenous furosemide reduces bronchial hyperresponsiveness to ACh in patients with chronic congestive heart failure. The mechanism of this effect appears to be related to the ion transport system of airway epithelium. PMID- 1405096 TI - [Clinical use of the measurement of functional residual capacity during non panting breathing--study on healthy subjects and respiratory patients]. AB - The functional residual capacity (FRC) has been measured by gas dilution technique (GA) and body plethysmographic technique (BP) using the panting maneuver (PA). However, this maneuver is difficult to perform for patients who experience discomfort in breathing, and in cases of chronic obstructive pulmonary diseases, the FRC value measured by panting maneuver overestimates the true FRC value. Thus, in order to minimize these factors, we measured FRC during non panting breathing (NP) using a BP device (BX-82, Minato Co., Osaka) and compared the results with the usual two methods. One hundred healthy subjects (Group I), 72 patients with restrictive ventilatory disorder (Group II, %VC = 62.7%) and 66 patients with pulmonary emphysema (Group III, FEV1.0% = 44.9%) were studied. All measurements were performed under 0.5 Hz respiratory frequency. The non-panting FRC measurement was performed by closing the mouth shutter of the BP for about 500 msec at the end of both the expiratory and inspiratory phase. From the box volume change and mouth pressure change, lisajous curves were formed and fitted by linear regression method. From this regression line, the volume of FRC was calculated. The obtained data had no significant differences among them, and there was a significant relationship between each technique. The correlation coefficient of non-panting breathing technique in Group III was slightly poor compared with the other techniques, and we therefore tried to re-classify Group III into small groups according to the severity of obstruction. It was subsequently found that this technique did not have the tendency to give a higher FRC value with increase in obstructive disorder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405097 TI - [Effect of hypoxia on the sensation of dyspnea during hypercapnic ventilatory response in normal subjects]. AB - We examined, in 32 normal adults, the effect of hypoxia on the sensation of dyspnea during hypercapnic ventilatory response (HCVR). The tests were conducted under two different levels of inspiratory O2 content, either hyperoxia (PETO2 greater than 150 Torr) or hypoxia (PETO2 50-55 Torr), with simultaneous assessment of dyspnea sensation by visual analogue scaling (VAS). The sensation was evaluated either in relation to VE standardized by predicted MVV (the slope of VAS-VE regression line or VAS at VE 40%) or in relation to PETCO2 (the slope of VAS-PETCO2 line or VAS at PETCO2 55 Torr). Concomitant hypoxia significantly enhanced both the mean value of delta VE/delta PETCO2 and that of delta P0.1/delta PETCO2. The sensation of dyspnea did not differ between the two conditions when it was evaluated in relation to ventilation, whereas it was markedly greater during hypoxic HCVR when it was evaluated in relation to PETCO2. The hypoxic augmentation of the sensation, compared at PETCO2 55 Torr, could be explained by increase of the motor output from the respiratory center, since it was positively correlated with the relative change of VE, VTTI, and delta P0.1/delta PETCO2 (r = 0.70, p less than 0.0001; r = 0.63, p less than 0.0001; r = 0.40, p less than 0.05, respectively). From these findings, we conclude that hypoxia does not have a direct dyspnogenic effect, at least in normal subjects. PMID- 1405098 TI - [Pathological examination of 11 autopsy cases of acute onset interstitial pneumonia of unknown etiology]. AB - In 11 autopsy cases of acute onset interstitial pneumonia of unknown etiology, all cases had thickening of alveolar septa with various degrees of lymphocytic infiltration and fibroblast proliferation. Only a few cases had edematous alveolar septa, which were weakly positive in alcian-blue staining. Intra alveolar, intra-alveolar duct and intra-bronchiolar organization was a characteristic finding. These findings may represent the repair phase rather than the exudative phase of diffuse alveolar damage. Localized bacterial pneumonia was superimposed in 3 cases, and neither Pneumocystis carinii nor viral inclusion bodies were identified in any case. The severity of fibrosis was not obviously correlated with the period of artificial ventilation. From these findings, terminal infection and oxygen therapy did not seem to significantly modify the course of acute-onset interstitial pneumonia. Further examination of autopsy cases as well as open-lung biopsy is important to elucidate the time course of acute-onset interstitial pneumonia. PMID- 1405099 TI - [Dyspnea and inspiratory muscle function during exercise in severe chronic obstructive pulmonary disease (COPD)]. AB - Role of inspiratory muscle function in the genesis of dyspnea in COPD patients has yet to be fully studied. The present study investigated the possible relationship between respiratory muscle function and the sensation of dyspnea (modified Borg Scale) during exercise in eight patients with severe COPD (FEV1 0.61L +/- 0.15L). The electrical activity of the diaphragm (EMGdi) was recorded with esophageal electrodes, and that of sternomastoid muscle (EMGsm) was recorded from the surface electrodes. The ratio of high frequency (150 to 350 Hz) to low frequency (20 to 47 Hz) power (H/L) of EMGdi and EMGsm was analyzed to assess inspiratory muscle fatigue, which was determined by a 20% fall of H/L ratio from the control value. Flow, volume, esophageal (Pes) and transdiaphragmatic pressure (Pdi) were measured. Tension time index (TTdi) was calculated from Pdi and the ratio of inspiratory time to total time for one cycle (T1/TTOT). At rest, we measured maximal esophageal pressure (Pesmax), maximal transdiaphragmatic pressure (Pdimax), maximal EMGdi (EMGdimax) and EMGsm (EMGsmmax). Progressive treadmill exercise test was performed, stating with 3 minutes' walk at a speed of 0.75 mph at 0% grade, subsequently increasing the velocity at a rate of 0.25 mph and the elevation at a rate of 4% per stage. Exercise was discontinued at maximum respiratory effort sensation. Six of the eight patients showed diaphragmatic fatigue at their maximal exercise. With diaphragmatic fatigue, these patients were extremely dyspneic (Borg scale 9 or 10), and terminated the exercise. There were high correlations between the Borg scale and VE/MVV, and Pes/Pesmax and EMGsm/EMGsmmax, however, TTdi and EMGdi/EMGdimax showed less correlation with the Borg scale.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405101 TI - [Clinical significance of scintigraphy in pulmonary aspergilloma]. AB - In order to study the scintigraphic findings related to the pathophysiology of pulmonary aspergilloma, chest scintigraphy with T1-201 chloride and perfusion lung scintigraphy were performed in 18 and 19 patients with pulmonary aspergilloma, respectively. In T1-201 scintigraphy, accumulation of T1-201 in the diseased areas related to Aspergillus infection was observed in 18 of 19 foci. Roentgenographic findings related to the accumulation of T1-201 in the lesion were thickness of the cavity wall and pleural thickening adjacent to the cavity, but they showed no relation to the size of the fungus ball, and 2 cases without fungus ball showed positive results. Moreover, in T1-201 single photon emission computed tomography, accumulation of T1-201 was demonstrated in the area surrounding fungus ball. In addition, findings of inflammation such as leukocytosis, elevated erythrocyte sedimentation rate, positive CRP and fever were observed in more than 50% of all cases. These results suggest that tissues surrounding the fungus ball, including the cavity wall and thickened pleura undergo inflammatory process secondary to infection by Aspergillus. Perfusion lung scintigrams showed decreased perfusion in all of 19 cases, which was more marked than that expected from the chest radiograph in many cases. In T1-201 myocardial scintigraphy, visualization of the right ventricle was observed in 15 of 18 cases. T1-201 chest scintigraphy and perfusion lung scintigraphy are useful for evaluation of the activity of the disease process, right ventricular overloading, and regional perfusion in pulmonary aspergilloma. PMID- 1405100 TI - [Clinical significance of respiratory infections associated with lung cancer patients]. AB - An attempt was made to interpret the clinical significance of secondary infections associated with lung cancer. The incidence of secondary infections was 51.4% in 214 in-patients with lung cancer in our institution in 1988 and 1989, and almost all of them had respiratory infections caused by commonly encountered bacteria. The incidence of infection was high in lung cancer of cell types other than adenocarcinoma, and in those with hypoalbuminemia, impaired cellular immunity and obstruction of the airway. The prognosis in patients with infection was much poorer than that in patients without infection. Major pathogens responsible for infection were Staphylococcus aureus including methicillin resistant S. aureus (MRSA), Haemophilus influenzae, Klebsiella spp. and Pseudomonas aeruginosa. These pathogens, except for H. influenzae, were isolated in the terminal stage in cases with airway obstruction and post cancer chemotherapy. The efficacy rate of 194 therapeutic regimens against infection was 57.7%. It was thus found that the efficacy rate in 1988 and 1989 exceeded that in the 1970s. The effectiveness was very poor for infections caused by S. aureus and P. aeruginosa, and for cases with airway obstruction and marked impairment of pulmonary blood flow. The efficacy rate of single-drug regimens was 57.1% (80/140) and that of combined regimens was 59.3% (32/54). The above results indicate that a new combined therapy which includes a beta-lactam antibiotic as well as measures to improve the general health of compromised hosts are required in the treatment of secondary infections in these patients. PMID- 1405102 TI - [Energy metabolism, respiratory heat loss, and lung functions in patients with chronic obstructive pulmonary disease and pulmonary fibrosis]. AB - Resting energy expenditure (REE) and respiratory heat loss (RHL) were measured in 17 patients with chronic obstructive pulmonary disease (COPD), 7 patients with pulmonary fibrosis (PF), and 8 normal healthy subjects, three hours after a light breakfast. Correlations between these values, and also predicted basal metabolic rate (PreBMR) and normalized lung functions were assessed. REE, REE/Pre BMR, RHL and RHL/REE in all patients increased significantly compared with those of control subjects. When all the studied subjects were combined, significant negative relationships were found between REE, REE/PreBMR, RHL and RHL/REE and percent predicted values of forced expiratory volume in one second (FEV1.0), between RHL and RHL/REE and percent predicted values of vital capacity (VC), and between REE/PreBMR, RHL and RHL/REE and percent predicted values of carbon monoxide diffusing capacity (DLCO). These results indicate that resting energy expenditure and respiratory heat loss increase in patients with COPD and PF in association with even slight to moderate deterioration of lung function. Therefore, elevated resting energy expenditure and respiratory heat loss need to be taken into account in determining caloric and water requirements of these patients. PMID- 1405103 TI - [Current status of pediatric home mechanical ventilation in Japan]. AB - The first nationwide survey of pediatric home mechanical ventilation (HMV) was conducted. From 35 out of 149 medical centers investigated, 49 cases of HVM were reported. The patients ranged in age from 1 to 20 years, and the causes of respiratory failure were neuromuscular diseases (51%), central hypoventilation (33%), respiratory disorders (10%) and cervical cord injury (6%). Since 1983 when 2 patients were discharged home on mechanical ventilation, more and more ventilator-dependent children have been sent home every year. However, home mechanical ventilation is not yet well recognized in Japan as an option for pediatric patients with chronic respiratory failure, and there are many problems to be solved. Firstly, very few, if any, hospitals have a designated home care team composed of physicians and other specialists. Secondly, the current health insurance system scarcely covers the cost of home ventilation. Thirdly, development of home use equipment, in particular, portable ventilators and monitors is imperative. There are 107 hospitalized patients in 56 institutions who are reportedly able to go home if a support system is established. A program for pediatric home mechanical ventilation should be urgently developed on a national basis. PMID- 1405104 TI - [Immunological reactions in patients with pulmonary aspergilloma]. AB - A 52-year-old man with pulmonary aspergilloma is reported. In immunoassays, type I, III and IV hypersensitivity reactions of Gell & Coombs were observed. The finding of such immunological reactions, especially type I hypersensitivity, has rarely been observed in this disease. The present study was performed to investigate these reactions, especially to determine whether type I allergy participates in pulmonary aspergilloma. We reviewed 126 cases of pulmonary aspergilloma reported in the Japanese literature between January 1980 and April 1991. The following results were obtained: Elevation of serum IgE was observed in 49% of the subjects examined, positive IgE RAST score in 28%, precipitating antibody against A. fumigatus in 79%, and positive lymphocyte stimulation test using A. fumigatus antigen in 68%. In conclusion, type I, III and IV hypersensitivity of Gell & Coombs appears to participate in pulmonary aspergilloma. The occurrence of type I hypersensitivity is not rare in this disease. PMID- 1405105 TI - [Contents of chemical mediators in sputum in a case of mycoplasma pneumoniae bronchiolitis resembling bronchial asthma]. AB - A case of Mycoplasma pneumoniae bronchiolitis with hypoxemia is presented. A 41 year-old man was admitted to hospital because of fever, productive cough and dyspnea with wheezing of one month duration. On admission, bronchial asthma was suspected on the basis of reversible airflow obstruction and sputum eosinophilia. However, despite treatment with bronchodilators, his condition did not improve. Chest film and computed tomogram revealed small nodular shadows and tramlines in the bilateral lower lung fields, and pulmonary function tests indicated peripheral airway obstruction. Serologic titer for Mycoplasma pneumoniae was 1:160. A diagnosis of bronchiolitis due to Mycoplasma pneumoniae was made. Improvement of lung function and roentgenographic findings was observed following administration of erythromycin and doxycycline. The concentrations of prostanoids in sputum were markedly higher than in cases of bronchial asthma, and decreased as he improved. These observations suggest that Mycoplasma bronchiolitis should be considered in the differential diagnosis of wheezing, and that measurement of prostanoids in sputum may be useful in the differentiation of infective bronchiolitis and bronchial asthma. PMID- 1405106 TI - [Two cases of chronic respiratory failure in intravenous methylphenidate (Ritalin) abusers]. AB - Marked obstructive ventilatory impairment and diffusion disturbance were noted in two intravenous methylphenidate (Ritalin) abusers. In one patient, chest radiogram demonstrated pulmonary emphysema accompanied by bullae and atelectasis, and spontaneous pneumothorax was also present. The primary finding in the other patient was interstitial shadows. Both patients began to note dyspnea during exertion after about 10 years of use. Since radiography also disclosed pulmonary emphysema in an ex-companion of Ritalin abuse, and since the onset was at relatively young ages, these pulmonary disorders are considered to have been a result of intravenous Ritalin abuse. Intravenous drug abuse should be considered in patients with precocious emphysema or obstructive ventilatory impairment accompanied by diffusion disturbance. PMID- 1405107 TI - [A case of hypersensitivity pneumonitis presenting with copious sputum and marked obstructive impairment of lung function]. AB - A 44-year-old male was hospitalized due to dyspnea and persistent cough with copious sputum (about 100 ml/day). Chest radiograph on admission showed hyperinflation and fine nodular shadows throughout both lungs, as well as a tram line appearance in the right lower lung field which suggested thickening of bronchial walls. Pulmonary function tests demonstrated moderate to severe reduction of %VC, FEV1.0 and PaO2. Fiberoptic bronchoscopy revealed inflammatory change in the walls of proximal bronchi. Although his dyspnea resolved rapidly, productive cough and impaired lung function were persistent and improved very slowly over the one-month-period following admission. After resolution, similar symptoms were provoked again 5 to 6 hours after returning to his home, suggesting the recurrence of hypersensitivity pneumonitis. Open lung biopsy was performed for the differential diagnosis of hypersensitivity, diffuse panbronchiolitis, and bronchial asthma, because neither transbronchial lung biopsy nor broncho-alveolar lavage was diagnostic. Histopathology of the open lung biopsy specimens revealed marked desquamation of bronchiolar epithelium in addition to bronchiolo alveolitis with epithelial granulomas, consistent with hypersensitivity pneumonitis. Copious sputum is a very uncommon clinical feature in hypersensitivity pneumonitis. We consider that the large volume of airway fluid was caused by epithelial ulceration of bronchioles and catarrhal bronchitis associated with hypersensitivity pneumonitis. PMID- 1405108 TI - [A case of chronic necrotizing pulmonary aspergillosis]. AB - A 70-year-old woman with diabetes mellitus who was following a therapeutic diet showed an infiltrative shadow in the right upper lung field on chest roentgenogram in April, 1986. She was diagnosed as having pneumonia and was treated for five months with several antibiotics, but the abnormal shadow on chest roentgenograms increased in size. Therefore, she was admitted to our hospital in October 1986. Although tubercle bacilli were not isolated from her sputum or from materials obtained by bronchoscopic examination, we made an initial diagnosis of pulmonary tuberculosis based on the findings of chest roentgenograms, tomographs and CT scanning. In spite of treatment with antituberculous drugs, the infiltrative shadow with cavity on chest roentgenograms continued to increase in size, and the patient developed occasional hemoptysis. Percutaneous needle biopsy was performed in February 1987 to establish a definite diagnosis, and the presence of Aspergillus fumigatus was confirmed by microscopic examination and culture. After treatment with miconazole and 5-FC for 3 to 4 months, the abnormal shadow on the chest roentgenogram gradually disappeared and was almost undetectable one year later. The clinical course of this patient was considered to be strongly indicative of chronic necrotizing pulmonary aspergillosis, which was described by Binder et al. in 1982. PMID- 1405109 TI - [A case of mediastinal malignant lymphoma with cardiac tamponade treated effectively with chemotherapy]. AB - A 78-year-old man was admitted to the Nishinomiya Municipal Central Hospital with main symptoms of chest pain and dyspnea. Chest CT revealed a large mediastinal mass shadow, and echocardiography revealed pericardial effusion. Serum LDH was elevated. Therefore, malignant lymphoma was suspected to be the cause of cardiac tamponade. VEPA chemotherapy was commenced. Half way through the course of chemotherapy, serum LDH was decreased, the pericardial effusion had disappeared, and the mediastinal mass was reduced in size. A biopsy specimen of the mediastinal tumor revealed malignant lymphoma of diffuse large cell type, and immunoperoxidase staining of frozen sections demonstrated B cell origin. The pericardial effusion had not increased in size after four months, when the patient developed pneumonia and died. Autopsy revealed pericardial and atrial involvement by tumor. In conclusion, this case is very unusual in that (1) pericardial involvement was suspected on admission; (2) the pericardial effusion disappeared with systemic chemotherapy; and (3) cardiac metastasis was demonstrated at autopsy. PMID- 1405110 TI - [An autopsy case of Marfan syndrome with bronchiectasis and multiple bullae]. AB - We report an autopsy case (27-year-old male) with Marfan syndrome, who died of chronic respiratory failure due to bronchiectasis and multiple bullae in both lungs. He had suffered from expectoration of massive amounts of sputum since the age of 15 years. At this time, chest roentgenogram had revealed bronchiectatic changes in the bilateral lower lung fields. Seven years later at the age of 22 years, the formation multiple bullae in both lungs were added to the bronchiectatic changes on chest roentgenogram. Administration of erythromycin (400 mg/day) was started in February, 1987, and the massive sputum volume markedly decreased according to appearance of bullous formation. He was admitted to our department because of deterioration with chronic respiratory failure and right heart failure at 26 years in December, 1989. Although various therapy was performed, he died of chronic respiratory failure in February, 1990. Autopsy findings were as follows: (1) cyclindrical bronchiectatic changes in bilateral lower lobes and (2) extensive multiple bullae in the subpleural areas with bronchiectatic changes in the middle and bilateral lower lobes, with no bronchiectatic changes in the bilateral upper lobes. Several pulmonary disorders accompanying Marfan syndrome have been reported, especially in children. However, the present case demonstrated that fetal pulmonary involvement by Marfan syndrome may not present until adulthood, and affect both airways and lung parenchyma. PMID- 1405111 TI - [A case of acetaminophen-induced pneumonitis]. AB - A 20-year-old woman took 1.2 g of acetaminophen for toothache. She subsequently developed a dry cough, pyrexia, and dyspnea. Chest X-ray revealed diffuse reticulo-nodular shadows in both lung fields. Broncho-alveolar lavage examination showed a marked increase in the total cell number and an increase in the percentage of eosinophils, neutrophils, and lymphocytes. Because drug-induced pneumonitis was suspected, all drugs were stopped and she was administered methylprednisolone. Consequently her symptoms resolved, and pulmonary function and chest X-ray findings improved remarkably. The lymphocyte stimulation test was positive for Norshin and its acetaminophen element. Based on these findings, the diagnosis of acetaminophen-induced pneumonitis was made. Acetaminophen intoxication is well-known, but to our knowledge this is the first reported case of acetaminophen-induced allergic pneumonitis in Japan. PMID- 1405112 TI - [A case of pulmonary metastasis from carcinosarcoma of uterus with subcutaneous implantation of tumor cells along the needle tract after percutaneous needle biopsy of lung]. AB - A 68-year-old female who had undergone total hysterectomy for carcinosarcoma five months previously was noted to have a solitary nodular shadow in the right lung on chest X-ray. Percutaneous needle biopsy of the lung was performed via the right anterior chest wall, and the histologic findings showed metastasis from carcinosarcoma of uterus. Two months after needle biopsy, a chest wall mass appeared of the site of puncture of the lung needle biopsy. The mass was resected to relieve the chest wall pain and the specimen showed carcinosarcoma of uterus histologically. We consider that tumor cells were implanted to the chest wall along the needle tract after percutaneous needle biopsy of the lung. The postoperative chest computed tomogram showed the route of tumor implantation from the metastasis of right lung into the right chest wall. Dissemination and chest wall implantation of malignant cells after percutaneous lung needle biopsy have been rarely reported. However there are no reports of tumor implantation of sarcoma. The possibility of implantation of tumor cells along the needle tract after percutaneous lung needle biopsy should be carefully considered in cases of carcinosarcoma. PMID- 1405113 TI - [A case of invasive broncho-pulmonary aspergillosis associated with influenza A (H3N2) infection]. AB - A 49-year-old man with high alcohol consumption was admitted with fever, cough and progressive dyspnea after a one week history of influenza-like symptoms. Chest X-ray film on admission showed diffuse peribronchial shadows and patchy infiltration in the right lower lung field. Chest X-ray film the following day and chest CT film on the 4th day of admission showed multiple nodular shadows and cavity formation. At bronchoscopy the bronchial surface was covered by white plaque, and Asp. fumigatus was subsequently cultured from BAL fluid. On the basis of suspected invasive pulmonary aspergillosis, anti-fungal agents were commenced. However, the shadows on chest X-ray increased, and the patient died on the 10th day of admission of respiratory failure and septic shock. Histological examination revealed bronchial wall invasion by hyphae of aspergillus and abscess formation in the pulmonary parenchyma. The precipitin antibody against aspergillus antigen was positive in reserved serum. Anti-Influenza A virus antibody (CF) was positive (X 256), and hemagglutination inhibition test of Influenza A (H3N2) was positive (X 2048) in serum on admission. The suppression of cellular immunity and destruction of the mucociliary system of airways induced by Influenza A infection was suspected to have predisposed to aspergillus superinfection. PMID- 1405114 TI - [A case of nephrotic syndrome associated with bronchogenic carcinoma]. AB - A 58-year-old fisherman was admitted because of an abnormal chest X-ray shadow on the right side. Bronchoscopic examination revealed tumor of right B7. Transbronchial biopsy showed squamous cell carcinoma. He was treated with four courses of CDDP and PEP. Two years later, he developed nephrotic syndrome and relapse of lung cancer. Proteinuria and pedal edema continued. Renal biopsy revealed the characteristic light and immunofluorescent microscopic features of membranous nephropathy. Oral administration of low dose etoposide resulted in reduction of the carcinomatous lung lesion and a decrease in proteinuria as well as pedal edema. PMID- 1405115 TI - [A case of intrabronchial dissemination of candida pseudohyphae presenting as respiratory failure]. AB - A 63-year-old man was admitted to our hospital because of fever, skin eruption, leukocytopenia and liver dysfunction. He was receiving H2-blocker for gastric ulcer of the time he developed his symptoms. The H2-blocker was discontinued because of its possible association with leukocytopenia, and steroids were administered. On the 4th day of hospitalization, he suddenly developed expiratory wheeze and dyspnea, resembling an asthmatic attack. WBC was 400/mm3 with 65% neutrophils. Chest X-ray showed hyper inflation and increased thickness of bronchiolar walls. Bronchodilators had no effect and the patient died of respiratory failure on the 8th day. At autopsy, most bronchioles were filled with candida pseudohyphae. The large airways and lung parenchyma were not involved, except for focal bacterial pneumonia. Histological findings suggestive of bronchial asthma such as constriction of bronchial smooth muscle or infiltration of eosinophils were not observed Candida infection was also found in the pharynx, stomach, bowel, and kidneys. Candidiasis is becoming a more important contributory cause of death in compromised hosts. Although rare, this case suggests that patients with bronchopulmonary candidiasis present with expiratory wheeze resembling asthmatic attack. PMID- 1405116 TI - [A resected case of teratoma of the lung]. AB - Teratoma of the lung in a 32-year-old female is reported. Abnormal shadow on chest X-ray film was noted at the age of 15 years. Her symptoms were subclinical fever, couch, hemosputum and frequent respiratory infections. Chest X-ray film and CT scan revealed a cyst with an intracystic solid mass in the left upper lung. Bronchogram demonstrated communication of the cyst with B5a and B5b bronchi. The left upper lobe was resected. Microscopic examination of the resected specimen revealed a mature teratoma of the lung. Teratoma of the lung is very rare. This case was diagnosed at surgery and was confirmed by microscopic examination. PMID- 1405117 TI - [A case of pulmonary eosinophilic granuloma with involvement of the ocular fundus]. AB - A 37-year-old man was admitted to our hospital because of abnormal shadows on chest X-ray film at routine medical examination. The chest X-ray showed diffuse granular shadows in the bilateral upper and middle lung fields. Chest CT showed multiple cystic lesions and nodular lesions. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed. Electron microscopic examination of BAL fluid revealed Langerhans' cells, and lung tissue specimen obtained by TBLB showed granuloma with infiltration of histiocytes and eosinophils. During the clinical course, the patient complained of cough and decrease of right visual acuity in association with an increase of abnormal shadows on chest X-ray. The lung disease gradually resolved after the cessation of smoking in spite of no therapy. In the right eye, an exudative lesion with retinal elevation was noted in the ocular fundus. Corticosteroid administration was effective for the treatment of this lesion. There was no pathological evidence of the right ocular lesion. However, the correlation of its clinical course with the lung disease suggests a relationship between the ocular lesion and pulmonary eosinophilic granuloma. PMID- 1405118 TI - [Clinical criteria for definition of idiopathic interstitial pneumonia (IIP)]. AB - Clinical criteria for definition of IIP proposed in 1991 by the Project Team for Diffuse Lung Diseases Organized by Japanese Ministry of Health and Welfare are reviewed. After the clinical roentgenological, and pathological researches of 92 IIP patients, we concluded that IIP patients were grouped into two clinical types, acute and chronic, by their clinical courses and characteristic pathological findings. The latter is, moreover, grouped into two types, typical and atypical, by their morphological characteristics. The acute type are represented by alveolitis with marked edema and cell infiltration of alveolar wall, and by hyaline membrane formation. "Typical" of chronic types only have typical pathologic changes of interstitial pneumonia and/or fibrosis represented by honeycombing. "Atypical" have both those interstitial changes and intra alveolar scar formation and fibrosis due to organized pneumonia and secondarily occurred emphysema such as bulla as well. The continuity in clinical courses between acute and chronic types are still obscure. PMID- 1405119 TI - [Postoperative management in neonate after open cardiac surgery]. AB - Recent advances in diagnostic method and preoperative care have allowed us to perform surgical repair in neonate. Important to the successful outcome of open cardiac surgery in neonate is cautious management in postoperative period. So we investigated the hemodynamics in the first 72 hours following open heart surgery for TAPVC, TGA and PAIVS. The hemodynamics in acute period are different according to patient age. Especially, early neonates under 14 days present low systemic blood pressure and high central venous pressure. So we must manage them according to their hemodynamic characteristics. PMID- 1405120 TI - [Malfunction of prosthetic valves: pathogenesis and diagnostic measure]. AB - Modality of the malfunction of prosthetic valve often reflects the specific features of its design and materials of the prosthesis. During past 17 years, a total of 499 cases of valve replacements were performed in our institute and among them, 50 cases received redo surgery, in which 52 prosthetic valves were replaced due to their malfunctions. Those replaced prosthetic valves were analyzed in terms of their pathogenesis, onset durations and diagnostic methods of each type of malfunction. The malfunctions included hemolytic anemia, thrombosis or tissue overgrowth and tissue failure of bioprostheses. Hemolytic anemia was experienced in 8 cases with Starr-Edwards (S-E) 2320 (n = 7) and Omni Science (n = 1) both in the aortic position and those prostheses were replaced at 1-9.6 (mean 4.5) postoperative years (POY). The linearized rate of the complication with the S-E 2320 was 3.0%/patient-years (p-y) and its actuarial event free rate was 62% at 11 POY. Operative findings disclosed cloth wear in 5 and perivalvular leakage in 5 cases. Fourteen Hancock (H) and 3 Angell-Shiley (A S) bioprostheses experienced tissue failure of valves and they were subjected to reoperation at 3.2-10.0 (mean 6.5) POY. The linearized rates were 4.1%/p-y for H and 4.5%/p-y for A-S with actuarial event free rates at 12 POY of 59 and 56%, respectively. Prosthetic valve thrombosis and/or tissue overgrowth were seen in 17 valves at 1.6-15.1 (mean 9.1) POY.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405121 TI - [A clinical experience of continuous warm blood cardioplegia in two cases of repeat aortic valve surgery]. AB - The continuous warm blood cardioplegia (CWBC) was used for myocardial protection during aortic cross clamping in two cases of repeat aortic valve operations with good results. Case 1: A 46-year-old man, who underwent an aortic valve replacement because of the rheumatic aortic regurgitation (AR) in 1978, have suffered from orthopnea due to para-prosthetic valvular regurgitation since 1983. He was revealed to have bi-ventricular hypertrophy with myocardial damage on ECG, EF 0.27 on UCG, PCWP 20 mmHg and severe AR on cardiac catheterization. Case 2: A 43-year-old man, who had an aortic valvuloplasty for the non-rheumatic incompetency in 1981, have had a recurrent regurgitation, resulting in left ventricular hypertrophy accompanied by chest pain. Both cases were reoperated upon, having aortic valve replacement with mechanical prosthetic valves through the re-median sternotomy, utilizing CWBC with good recovery. CWBC provides an ideal circumstances for myocardial oxygen utilization during aortic cross clamping and moreover a benefit that needs not the wide dissection of the heart in a redo case because it has no need of topical cooling and ventricular defibrillation following aortic declamping. In conclusion, CWBC is very useful in a repeat aortic valve surgery. PMID- 1405122 TI - [Pulsed Doppler echocardiographic observation of left ventricular filling dynamics after aortic valve replacement in patients with chronic aortic regurgitation]. AB - The 23 patients who underwent aortic valve replacement (AVR) for aortic regurgitation (AR) from 1977 to 1990 were studied with pulsed Doppler echocardiography. The patients were divided into two groups. The A group consisted of 5 patients whose end-systolic volume index (ESVI) were more than 200 ml/m2 and/or left ventricular ejection fraction (EF) were less than 0.35 before AVR. The B group consisted of 18 patients whose ESVI were less than 200 ml/m2 and EF were more than 0.35 before AVR. A Doppler volume sampler was placed at the center of mitral orifice to measure the transmitral inflow velocity after AVR (mean 28 months). Left ventricular filling dynamics were assessed by the peak velocity in the rapid filling phase (R), the peak velocity in the atrial contraction phase (A) and the ratio of A by R (A/R ratio) of mitral flow velocity pattern. The deceleration rate of early diastolic rapid inflow (DeR) determined as the slope a straight line drawn between the peak of early diastolic inflow and a point at half peak velocity on the fall side of the envelope. Result was as follows; 1) The DeR showed significant correlation with the EF (r = 0.56, p < 0.01). The DeR showed significant inverse correlation with the ESVI (r = -0.52, p < 0.05). 2) The R velocity (mean 43.9 +/- 7.9 cm/sec) in group A was significantly lower than in group B (mean 61.4 +/- 18.6 cm/sec), (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405123 TI - [Analysis of mononuclear cell subpopulations in bronchoalveolar lavage fluid in acute rejection after lung transplantation in rats]. AB - Changes of components of mononuclear cell subpopulations in bronchoalveolar lavage (BAL) fluid were analyzed during acute rejection after lung transplantation in an inbred rat model. All allotransplants (BN/LEW) developed progressive acute rejection from day two until day six, demonstrating severe perivascular and peribronchiolar infiltration of mononuclear cell subpopulations. The number of total cells and activated macrophages increased significantly in BAL fluid from vascular phase until alveolar phase of acute rejection. The number of T and B lymphocytes in BAL fluid increased in alveolar phase, but not in vascular phase of acute rejection. The increase of the number of activated macrophages in BAL fluid may be useful as a monitor of acute allograft rejection following lung transplantation. PMID- 1405124 TI - [Inhibition of acute rejection of heart graft in rats without immunosuppressants after intrathymic myocardial cell inoculation in the neonatal period]. AB - There have been no successful cases reported of organ transplantation in application of neonatal immunological tolerance. Isolated myocardial cells from Lewis (LEW/Crj) rat hearts were inoculated into the thymus of incompatible King (WKAH/Hkm) rats. Ten weeks later the heart from LEW donor was transplanted heterotopically to the WKAH rat that had inoculated intrathymic myocardial cells without immunosuppression (n = 4, Group 1). Group 2 was made up of 4 isografts of heart transplantation (nontreated isograft). Group 3 was made up 4 allografts of heart transplantation (nontreated allograft). The animals were killed 7 days after transplantation, and early rejection was evaluated by accumulation of iodine-125 (125I)-labeled antimyosin antibody (AMA) uptake and confirmed by histological examination. In Group 1 & 2, the value of I-125 AMA uptake ratio was small (Group 1; RV: 1.28 +/- 0.28, IVS: 1.29 +/- 0.28, LV: 1.43 +/- 0.25, Group 2: RV: 1.14 +/- 0.07, IVS: 0.95 +/- 0.06, LV: 1.16 +/- 0.21). This level of the value indicates that the rejection does not occur. On the other hand, in Group 3, the value was high (RV: 4.63 +/- 1.92, IVS: 4.42 +/- 1.75, LV: 4.45 +/- 1.73) compared with Group 1 & 2. This level indicate that the rejection is severe. In the histological studies, Group 3 showed necrosis of myocardial cells, while Group 1 with neonatal immunological tolerance showed only very mild lymphocytic infiltration. The histology of thymic tissue in Group 1, the LEW myocardial cells are surviving in the WKAH rat thymus. PMID- 1405125 TI - [Mitral valve surgery using combined superior-transseptal approach to the left atrium]. AB - Although various approaches to the mitral valve surgery have been tried in the past, it still may be difficult to obtain a good surgical field, particularly in cases of small left atrium or reoperation. We performed mitral valve surgery in 6 patients using the combined superior-transseptal approach to the left atrium proposed by Berreklouw. Exposure of the mitral valve was excellent and the operative procedure was simple in all cases. There were no differences in bleeding volume, length of operation or complication of arrhythmia between patients treated with this new approach and a group treated with conventional approach in our institute. PMID- 1405126 TI - [Clinical experiences of a new vascular graft prosthesis fabricated from ultrafine polyester fiber (Toray graft)]. AB - A new low porous vascular prosthesis made of a textile of ultra-fine fiber was used clinically in ten patients for whom replacement of the ascending and/or arch aorta were performed. There were no operative deaths after initial operations, but one patient died after a second operation in which replacement of the thoraco abdominal aorta was performed. Nine survived patients are well for 50 days to 10 months postoperatively. The new vascular graft prosthesis was very soft and pliable in clinical use, and the surgical needle penetrates easily the prosthesis. Although the new graft prosthesis can be used without preclotting under full heparinization, porosity of the graft, 100 ml/min/cm, revealed initial oozing of blood for a while just after releasing an aortic clamp. Therefore, preclotting of the graft is recommended under full heparinization. Because of rapid, even, and stable formation of neo-intima in the new graft confirmed by experimental studies of Noishiki et al., and soft and pliable characteristics of the graft, a wide-spread clinical use of the new graft is recommended in the surgery of aortic aneurysms as well as reconstruction of the congenital malformations. PMID- 1405127 TI - [A case of undifferentiated carcinoma of the thyroid with compression stenosis of the cervical and mediastinal trachea which was dilated by the expandable metallic stents]. AB - The patient was a 64-year-old male with undifferentiated carcinoma of the thyroid which constricted the trachea. The radiation therapy did not reduce the size of the tumor, and did not improve the dyspnea. Bronchoscopy and tomography showed a compression stenosis of the cervical and mediastinal trachea. It was difficult to insert the T-tube because of the large mass of the neck. Therefore, three EMSs were inserted into the stenotic area of the trachea. Immediately after the insertion of the EMSs, the lumen of the trachea was dilated, and the dyspnea was improved. The patient died of the tumor 7 weeks after the insertion of the EMSs. Autopsy showed that the trachea was dilated by EMSs. PMID- 1405128 TI - [An experience of rapid, two-stage arterial switch operation for transposition of the great arteries and intact ventricular septum beyond the neonatal period]. AB - A 2-month-old girl with transposition of the great arteries and intact ventricular septum was successfully repaired by rapid, two-stage arterial switch operation. Balloon atrioseptostomy and ligation of the ductus arteriosus was done elsewhere on 14th and 29th day after birth. On her first admission to our hospital at 2 months of age, left ventricular-right ventricular pressure ratio (LVp/RVp) was almost 0.5 and left ventricular posterior wall thickness (LVPWT) by echo cardiography was 3.5 mm. Because of these date, we selected rapid, two-stage arterial switch operation. On 74 days, the first-stage preparatory operation (pulmonary arterial banding and right modified Blalock-Taussig shunt) was undergone with the resultant LVp/RVp of 0.97. During a few days after the first stage operation, left ventricular ejection fraction (LVEF) by echocardiography was reduced to nearly 30%. But after this phase left ventricular function recovered rapidly and LVp/RVp, LVPWT and LVEF was 1.18, 6.3 mm and 66% on the 7th day. On the 9th day, the second-stage arterial switch operation was undergone as usual as in neonatal period without hard adhesion. Her postoperative course was uneventful. PMID- 1405129 TI - [A case of sliding commissuroplasty for the chordal rupture in the paracommissural area]. AB - A 67-year-old female patient underwent mitral valvuloplasty for mitral regurgitation due to the chordal rupture at the posterior commissure. Sliding commissuroplasty was made to avoid large annular plication. Carpentier's prosthetic ring (30 mm) was sutured to remodel the annulus and to reinforce repair. Postoperative Left ventriculogram revealed no regurgitation. Sliding commissuroplasty is effective for mitral regurgitation due to commissural chordal rupture. PMID- 1405130 TI - [A case of traumatic right diaphragmatic hernia diagnosed by pleurography]. AB - The diagnosis of traumatic diaphragmatic hernia is relatively easy on the left side, but is often difficult on the right, partly because the herniated organ is usually the liver. Recently, we experienced a relatively rare case of traumatic right diaphragmatic hernia and found that pleurography was useful for its diagnosis. This case is reported here together with some discussion of the literature. PMID- 1405131 TI - [A surgical case of coronary sinus ASD]. AB - A case of coronary sinus ASD in a 56-years-old woman is reported. This defect was detected during operation for the first time. In this case, a LSVC was absent and coronary sinus opened into the left atrium. The defect was closed using a pericardial patch. PMID- 1405132 TI - [A case report of simultaneous procedure of Cabrol's operation and aortic arch replacement: method to reduce the duration of ischemic cardiac arrest]. AB - A 57-year-old female underwent simultaneous Cabrol's operation and aortic arch replacement for aortic dissection. She was admitted with complaint of back pain. Aortography demonstrated acute dissecting aneurysm of the ascending, arch and descending aorta (DeBakey type I) as well as aortic valve regurgitation (Seller's II degree). The operation was undertaken using cardiopulmonary bypass (CPB) under hypothermia with selective cerebral perfusion. A new method to reduce the duration of ischemic cardiac arrest was applied. Initially a low-porosity woven Dacron tube graft (8 mm) was anastomosed to coronary arteries. Blood of CPB was perfused to this graft. This coronary perfusion contributed to shorten ischemic cardiac arrest time and cardiac function was favorable. This method to reduce the duration of ischemic cardiac arrest brought about good result. PMID- 1405133 TI - [A case of successful surgery for tetralogy of Fallot with single atrium, azygous connection and partial anomalous pulmonary venous drainage in atrio-visceral heterotaxic syndrome]. AB - A 2-year-old girl of heterotaxia associated with complex anomalies was reported. Major cardiac anomaly was tetralogy of Fallot (TOF), which associated with the interruption of the inferior vena cava, persistent left superior vena cava (PLSVC), common atrium and partial anomalous pulmonary venous drainage (PAPVD) to the coronary sinus. The two dimensional echocardiogram displayed the characteristic views of TOF and the additional interesting abnormalities near the mitral ring. The markedly enlarged and protruded coronary sinus by the association of PLSVC and PAPVD overlay along the posterior mitral leaflet and the abnormal muscular septum surrounded immediately above the anterior mitral leaflet. These structures created a sort of supramitral ring structure, although this was not important hemodynamically because of the association of single atrium and TOF preoperatively. At the operation the coronary sinus roof was resected along the posterior mitral leaflet as well as the abnormal muscular flange. The atrial septum was created with a porcine pericardium and the left superior vena cava was ligated. The postoperative course was not eventful. PMID- 1405134 TI - [A case report of aorto-pulmonary window associated with atrial septal defect]. AB - The patient was a one-year-old boy, who underwent surgery with a diagnosis of atrial septal defect (ASD). During operation, aorto-pulmonary window (A-P window) which had not been detected by the preoperative examinations, was found. Therefore, the A-P window was divided prior to closing ASD. The patient is in good condition six months after the operation. The causes of the inaccurate preoperative diagnosis were discussed. PMID- 1405135 TI - [Surgical treatment of double aortic arch: report of a case associated with frequent respiratory infections]. AB - A seven-month-old baby with double aortic arch was reported. He was admitted to our hospital with complaint of frequent respiratory infections shortly after birth. On examination, bronchofiberscopy revealed compression of the trachea and left main bronchus from behind and angiography showed complete vascular ring, namely double aortic arch with no other cardiac anomaly. Soon after the operation, stridor disappeared at rest, but mild stridor persisted on exertion. Three months later, he was re-admitted to our hospital because of pneumonia. Therefore, close observation is required for the patients with double aortic arch, even if the operation is effective. PMID- 1405136 TI - [A case of surgical repair for combined septal perforation and cardiac rupture after myocardial infarction]. AB - The successful surgical repair of the combination of septal perforation and cardiac rupture after myocardial infarction was underwent on a 73-year-old man. Complete correction could be performed under the fibrillated heart state employing cardiopulmonary bypass, resulted in the early postsurgical cardiac performance. PMID- 1405137 TI - [A case of traumatic aortic valve rupture]. AB - A case of aortic valve rupture as a result of blunt trauma by motorcycle accident is presented. A previously healthy 18-year-old male developed severe congestive heart failure 46 days after the initial trauma. There were crescentic tears in the right and non-coronary cusps parallel to and along the whole length of the cusps. The valve was excised and replaced with a 21 mm St. Jude Medical prosthesis. Following the procedure he made an relatively uneventful recovery and was discharged on the 83rd postoperative day. The possibility of damage to the heart valves in traffic accidents must be borne in mind since rapid deterioration can occur and early surgical therapy is essential. PMID- 1405138 TI - [A successful two-staged Fontan procedure for tricuspid atresia with bilateral superior venae cavae and left pulmonary arterial stenosis]. AB - A 10-year-old boy with tricuspid atresia (type I-b), bilateral superior venae cavae and left pulmonary arterial branch stenosis was treated successfully by a two-staged Fontan procedure. At 7 years of age, left Glenn shunt was performed after creation of a communicating vessel between the right and left superior vena cava, using a GORE-TEX graft of 10 mm of diameter. Three years later, after having confirmed graft patency, Fontan procedure was achieved without any problems. We think the innominate vein creation by an artificial material was a key design for the following successful two-staged Fontan procedure in this case. PMID- 1405139 TI - [A case of small adenocarcinoma of the lung with giant bullae]. AB - A 52-year-old male underwent right upper lobectomy for giant bullae which involved almost half of thoracic cavity and covered over the right upper lobe. Postoperative histopathological examination revealed emphysematous bullae of right upper lobe and adenocarcinoma (6 mm in diameter) was found in the bullae wall under the pleura. Since there was no metastasis in bronchial lymph nodes of upper lobe, additional procedure for lymph node dissection was not performed. Patient has been healthy for eight years after operation and there is no evidence of recurrent tumor. It is difficult to define the small lesion of neoplasma with giant bullae of lung. Therefore, the patient involved with bullae may require preoperative and intraoperative attentive investigation for possible malignant lesions. PMID- 1405140 TI - [Long-term results in 1,400 patients with coronary artery bypass grafting: saphenous vein vs arterial grafts]. AB - To analyze and compare the effects of saphenous vein grafts (SVG) and arterial grafts (AG) on the long-term results of the coronary artery bypass grafting (CABG), retrospective nonrandomized studies were performed in 1,400 consecutive patients with CABG in terms of reoperation, postoperative transluminal coronary angioplasty (PTCA) to the grafts, actuarial survival rate, and cumulative event free rate. AG was used frequently in recent cases in which more diffuse and multiple vessel disease were encountered. No statistically significant differences were noted in any of the reoperation free rate, actuarial survival rate, success rate of the PTCA, and cumulative event free rate between SVG and AG, because the long-term results of the SVG was apparently better than reported Caucasian's long-term results, while those of the AG were as good as Caucasian's. Reoperation and PTCA for the AG were performed less than one year after the CABG in most cases and restenosis after the PTCA was rare. In contrast, those for the SVG were mainly done late postoperative period, and the incidence of the restenosis after the PTCA was very high. These results indicated that the main cause of the graft failure in the AG was technic-related, and that of the SVG was graft's atherosclerosis. We conclude from this study that AG should be indicated more extensively than SVG, but proper indication and application of the AG in various situations and technical improvement to avoid stenosis at anastomosis are important to improve the long-term results of the CABG. PMID- 1405141 TI - [Late results of coronary artery bypass grafting with the internal thoracic artery]. AB - Between November 1981 and December 1991, 755 patients underwent isolated coronary artery bypass grafting. We compared postoperative events, graft patency and survival rates of the patients who received at least one internal thoracic artery graft (n = 517) with those of the patients who had only saphenous vein bypass grafts (n = 238). No significant difference was found between the 2 groups in patient's age at the operation, female ratio and the incidence of emergency operation. The operative mortality was not significantly different in either group. Graft patency was better for internal thoracic artery grafts than for SVG (ITA grafts 97.1%, SVG 85.6% p less than 0.0001). Graft-LAD patency rate was also better for ITA grafts than for SVG (ITA grafts 97.7%, SVG 86.8%, p less than 0.0001). The incidence of late cardiac events (late cardiac death, reoperation, myocardial infarction) is lower in patients with ITA. Furthermore, patients who received ITA grafts had a better survival rate at 8 years (91.1% versus 85.3%, p = 0.048) than those who had vein bypass grafts alone. We conclude that the use of ITA grafts enhances the long-term benefits including long-term survival rate. This is the first observation in Japanese population. PMID- 1405142 TI - [Comparative studies of various conduits for myocardial revascularization with Kawasaki disease]. AB - Between October 1976 and December 1991, 36 patients with Kawasaki disease underwent coronary bypass surgery. Comparisons were made from the postoperative morphologic condition of 4 conduits; saphenous vein graft (SVG n = 27), left internal thoracic artery (LITA n = 22), right internal thoracic artery (RITA n = 5) and gastroepiploic artery (GEA n = 8). The patency rate of arterial grafts was 100% at 1 month after surgery, and kept as high as 94.7% at 1-3 years after surgery. On the other hand, the patency rate of SVG was 90% at 1 month, but decreased to 52% at 1-3 years postoperatively. Arterial grafts sometimes showed string sign at 1 month after surgery, but the length and the diameter increased during 1 year after surgery. The internal thoracic artery showed superior flow potential compared with GEA. Thus, the internal thoracic artery is the first choice and GEA is the second as the graft material with Kawasaki disease. Long term result of SVG was very poor, so coronary revascularization only by the arterial grafts is recommended. PMID- 1405143 TI - [Coronary artery bypass grafting in patients with severe left ventricular dysfunction: internal mammary artery vs saphenous vein, evaluation immediately after surgery]. AB - Comparative studies of the changes in left ventricular (LV) function immediately after aortocoronary bypass graftings (CABG) and early postoperative results were carried out in two groups of patients with severe LV dysfunction (ejection fraction less than 0.4), which consisted of 9 patients received internal mammary artery grafts (IMAG) to at least LAD and 14 with saphenous vein grafts (SVG) only. The utilization of IMAG was limited to the patients with stable preoperative hemodynamics, whereas SVGs were used even in the emergency CABG. Free flow of IMAG measured during operation was 55.7 +/- 25.5 ml/min, which was significantly lower than that (83.5 +/- 27.3) of SVG to LAD. Cardiac index, LV stroke volume index and LV stroke work index immediately after surgery were sufficiently maintained and recovered almost similarly in both groups. Postoperative peak CK-MB (19.7 +/- 10.4 IU/L) in IMAG group was significantly lower than that (23.9 +/- 10.7) in SVG group. There was no significant difference between the two groups in the incidences of postoperative IABP and noradrenaline dependence. There were two hospital deaths in SVG group, whereas no hospital death was experienced in IMAG group. These results indicate that an application of IMAG to LAD in the patients with severe LV dysfunction surely induces satisfactory recovery of hemodynamics immediately after CABG as well as SVG, provided that use of IMAG is limited to the patients with stable preoperative hemodynamics. PMID- 1405144 TI - [Choice of conduit in coronary bypass surgery]. AB - Since 1987, arterial conduits have been used in 78 of 130 cases receiving coronary bypass surgery, including 25 treated by arterial conduits alone. The use of arterial conduits was mainly indicated to the anterior descending coronary artery (LAD), but the saphenous vein had to be used in 39 percent, 47 of 120 cases receiving bypass grafting to the LAD for various reasons including a combination of multiple obstructive arteriosclerosis, multiple bypass graftings in the aged, unstable angina, emergency operation and no suitable artery for a conduit as indicated by preoperative angiography. Hereafter, arterial conduits for coronary bypass grafting to LAD should be used in many more cases to the best possible advantage. PMID- 1405145 TI - [Selection of graft materials in case of emergency coronary bypass surgery following failed angioplasty]. AB - The clinical characteristics of selection of graft materials were analysed for patients undergoing emergency coronary artery bypass surgery (CABG) following failed coronary angioplasty (PTCA). Ten emergency CABGs were performed from January 1983 to December 1991. Perioperative variables and follow-up were compared to 18 patients undergoing elective CABG after PTCA. The emergency group had shorter operative time (p less than 0.01) and shorter bypass time (p less than 0.05). Moreover the emergency group had decreased use of the internal thoracic artery (ITA) (40% vs 94.4%, p less than 0.01). There was no use of bilateral ITAs in the emergency group. There was not significant difference in hospital mortality and medium term follow-up between two groups. In conclusion, emergency CABG carries a significantly less use of ITA graft than elective CABG although ITAs are superior to SVGs about long term patency rate. So it is desirable that arterial graft should be used under an appropriate selection at emergency operation. PMID- 1405146 TI - [Coronary artery bypass grafting: does the use of arterial graft for coronary artery bypass grafting increase surgical risk?]. AB - Since April in 1988 coronary artery bypass grafting (CABG) was performed in 177 patients and the clinical results were compared in SVG-group (n = 37) in which only saphenous vein graft (SVG) was used as a graft conduit and AG-group in which one arterial graft (AG-1 group, n = 92) or more than two arterial grafts were used (AG-2 group, n = 48). In SVG-group the age was older than that in AG-group, while coronary vessels were most involved in AG-2 group and the mean number of distal anastomosis increased more in AG-group. The total pump time and aortic cross clamping time showed no significant differences among the groups. Furthermore, the occurrence of perioperative myocardial infarction, requirement of intra-aortic balloon pumping, frequency of re-chest open for hemorrhage, or sternal infection showed no significant differences among the groups. Postoperative hospital deaths were in four (three cardiac deaths) of SVG-group and four (one cardiac and two graft-versus-host disease) of AG-group. These results suggest that the use of AG does not increase surgical risk and AG can be positively used for CABG. PMID- 1405147 TI - [Coronary artery bypass utilizing vein grafts: why didn't we use an arterial graft?]. AB - Internal thoracic artery (ITA) grafts for coronary artery bypass grafting (CABG) are superior to SVG in the long-term patency and survival. In spite of our effort to utilize ITA whenever possible, we still have some cases which have to receive only vein grafts. Among the consecutive 201 patients undergoing CABG in the past three years, 32 patients (16%) received only vein grafts. We compared these patients (SVG group) with those who received ITA grafts (ITA group). The SVG group consisted of all emergency cases and many cases with single and double vessel disease. In the SVG group, perioperative use of IABP was more frequent and operative mortality was higher, although the number of grafts was fewer (2.66 vs 3.61) and aortic cross clamping time was shorter in this group. Main reasons for selecting only vein grafts were emergency surgery, inadvertent injury of ITA, inadequate ITA free flow etc. Technical refinement in the preparation of ITA is important to make possible wider application of arterial grafts for CABG. PMID- 1405148 TI - [Myocardial revascularization for ischemic heart disease without in situ internal thoracic artery grafting]. AB - CABG was performed in 327 patients from 1989 to 1991. We used ITA grafts for the arterial conduit whenever this was possible. Since ITA grafting has become a routine procedure in CABG, we investigated the reasons why in situ ITA grafts were used in some of our patients. The number of CABG patients without in situ ITA grafts was 42 in 1989, 35 in 1990, and 9 in 1991. There was three main reasons for this: 1) problems with the coronary arteries or myocardium, 2) problems with the ITA grafts, and 3) problems with the patient. Although ITA grafts were not used in these cases, the indications for ITA grafting have been changed by our review. Use of ITA grafts need not be restricted for reasons of age or native coronary artery problems, but some patients will still be unsuitable for these grafts. PMID- 1405150 TI - [Physiological characteristics of arterial graft for coronary artery bypass surgery]. AB - Arterial grafts have been used widely for coronary artery bypass grafting (CABG) because of their excellent long patency. However, some clinical reports suggest that blood flow in arterial grafts may not be adequate compared with aorto coronary bypass grafting. Pressure in arterial grafts was measured in patients undergoing CABG. The pressure tracing in the ascending aorta (AA) was maintained during diastole. The systolic pressure wave in ITA and GEA was narrow, while the diastolic pressures fell rapidly: the diastolic pressure in GEA was lower than in ITA. The area under the pressure wave was measured in diastole and in systole. Although there was no significant difference in systolic areas, the diastolic area were lower in ITA than in AA, and lower in GEA than in AA and in ITA. These results clarified that arterial grafts which belong to the systolic-dominant systemic circulation have disadvantages over aorto-coronary bypass grafts, in terms of physiological suitabilities to the diastolic-dominant coronary circulation. PMID- 1405149 TI - [Analysis of preoperative predictors influencing early patency of coronary artery grafts]. AB - Under the recent trend of popular use of arterial grafts, we investigated the predictors of coronary artery bypass graft patency using modified scoring system of Greenlane hospital. A total of 127 grafts including 58 arterial grafts (53 in situ ITA, 3 free ITA, and 3 GEA) and 69 saphenous vein grafts were placed in 43 patients for average of 2.95 grafts per patient during the period from April 1990 to December 1991. Early patency of arterial grafts (98.3%) were significantly better than that of saphenous vein grafts (91.3%) (p less than 0.01). With regard to recipient vessels, both coronary flow-demand score (= score of the size of perfused myocardium x viability index x index of proximal stenotic lesion/3) and distal run-off score influenced early graft patency significantly. It seems that better patency of arterial grafts were reflected on the bias that these grafts were preferentially placed on larger coronary arteries such as the left anterior descending artery, not on the advantage of arterial grafts. PMID- 1405151 TI - [Coronary artery bypass surgery with bilateral internal mammary artery]. AB - Increasing number of coronary artery bypass surgery has been performed utilizing more arterial grafts because of poor long term patency rate of saphenous vein grafts. The risk of bilateral internal mammary artery grafting was studied in two groups of patients who were matched for recognized risk factors such as year of operation, age, gender, extent of coronary artery disease, left ventricular function, completeness of myocardial revascularization, and history of congestive heart failure. The patient groups differed in the fact that they received on internal mammary artery graft or two internal mammary artery grafts. The operative mortality rate was zero in either group. Analysis of operative and postoperative morbidity demonstrated no significant differences except for a slight increase in transfusion requirement, rate of wound infection and use of catecholamine in the group receiving two internal mammary artery grafts (p = 0.1, 0.1 and 0.05, respectively). We conclude at this moment that bilateral internal mammary artery grafting does not increase surgical mortality but increases the use of catecholamine comparing with the ipsilateral internal mammary artery grafting. Since the cases analysed in this study are limited, definitive conclusion should be deferred. PMID- 1405152 TI - [Sequential coronary artery bypass using gastroepiploic artery]. AB - We carried out sequential coronary bypass grafting using the gastroepiploic artery (GEA) as an in situ graft in seven patients. Four patients had sequential graft from the right coronary to the circumflex. Three patients were anastomosed to two or three peripheral branches of the right coronary artery. There were no early deaths. Postoperative angiograms revealed that the patency rate was 92.3% (12/13 anastomoses). Sequential GEA grafting is available to anastomose the peripheral branches of the right coronary and the circumflex where the in situ internal thoracic artery is difficult to access. Therefore, this procedure will be indicated for multiple coronary artery bypass grafting. PMID- 1405153 TI - [Problems and prevention in using arterial grafts for coronary artery bypass grafting]. AB - The arterial graft has proved to be superior to the saphenous vein graft for coronary bypass grafting (CABG), because of its excellent long-term patency. However, there mains controversial on the choice of the arterial grafts. Six hundreds and twenty seven patients who had CABG using both arterial grafts and saphenous vein grafts, operated upon over 11-years period between 1980 and 1991, have been analysed. Some disadvantages and complications associated with the use of arterial grafts were demonstrated in our series. We discussed, the flow capacity, myocardial protection and postoperative complications in using arterial grafts for CABG. PMID- 1405154 TI - [Coronary revascularization with arterial bypass graft as a routine]. AB - In the period from December 1989 until December 1991, coronary revascularization were performed on 68 patients using arterial grafts as a routine. The ages of the patients ranged from 43 to 85 years (average: 67.1 years), and there were 38 males and 30 females. Twenty-seven patients had angina pectoris, 32 had old myocardial infarction and 9 had acute infarction. The bypass grafts used were 69 left internal thoracic artery (LITA) grafts, 39 right internal thoracic artery (RITA) grafts, 68 right gastroepiploic artery (RGEA) grafts and 3 saphenous vein (SV) grafts. Thus, 179 grafts were used and an average of 2.6 bypasses were created per patient. There was only one death in 57 elective operations. Investigation of postoperative graft patency was performed in the 167 grafts that could be examined angiographically after surgery. Only 7 were obstructed, yielding a patency rate of 95.9%. By using both the ITA and RGEA, in situ anastomoses with the most of the coronary arteries could be performed. This operative form is considered to be useful technique and may be expected to produce favorable long-term results. PMID- 1405155 TI - [An emergency coronary artery bypass for failed percutaneous transluminal coronary angioplasty with intractable ventricular tachycardia and fibrillation]. AB - A 73-year-old man with effort angina after myocardial infarction is admitted for percutaneous transluminal coronary angioplasty (PTCA). During PTCA, the left anterior descending artery (LAD) was completely occluded. He was suffered from severe cardiogenic shock with systemic cyanosis and loss of consciousness. Under assist of intraaortic balloon pump (IABP) and cardiac massage, he was transferred to an operating room. Before the start of operation, cardioversion were required 13 times because of repeat attacks of ventricular tachycardia and fibrillation. Coronary artery bypass was completed in 177 minutes after total occlusion of the LAD. At the 5th postoperative day, IABP could be discontinued, and at the 8th postoperative day, the patient was weaned from mechanical ventilation. He was transferred to the prior hospital for rehabilitation on the 65 days after operation. We must try to perform CABG for salvage of myocardium, even if a patient falls in severe cardiogenic shock presenting intractable ventricular tachycardia and fibrillation. PMID- 1405156 TI - [Right coronary spasm immediately after coronary artery bypass grafting for the left coronary artery]. AB - Right coronary spasm immediately after coronary artery bypass grafting for the left coronary artery in a 39-year-old male is described. After the patient was returned to ICU, ECG at leads II, III, and aVF changed suddenly, ventricular tachycardia (right ventricle origin) and cardiac arrest ensured. As neither administration of drug nor application of D.C. was effective. The chest was reopened at ICU. Though there was sufficient flow in the left coronary artery bypass graft flow, the right ventricle did not constrict at all. Right coronary artery spasm was diagnosed, and, upon application of the direct cardiac massage and D.C. at the cardiac surface, cardiac rhythm and blood pressure were normalized. IABP was inserted to improve cardiac function, and the chest was closed. In addition, nitroglycerin and diltiazem were infused continuously. No spasm has occurred after this episode, and the patient has been discharged and is doing well. PMID- 1405157 TI - [Coronary artery bypass grafting in a patient with Kawasaki disease]. AB - A 3-year-girl admitted because of angina at rest. She had been diagnosed as Kawasaki disease at the age of 3 months. At that time, a coronary aneurysm was detected by echocardiogram and aspirin had started to administer. At the age of 4 months, a cardiac arrest occurred after severe heart attack because of inferior myocardial infarction. At the age of 2 years and 6 months, she started to complain of a chest pain even at rest. Coronary angiography was performed, and it showed total occlusion of RCA and LAD. However, LAD was vaguely filled by collateral flow from diagonal branch, and 201Tl scintigraphy showed myocardial viability of anteroseptal area. At operation, the size of ITA was 1.2 mm in diameter. Coronary artery bypass grafting to LAD by ITA was performed. Three weeks postoperatively, graft patency was confirmed by coronary angiography. The girl discharged with good ability of exercise. The ITA seemed to be the first choice of conduit for CABG even in a small child, and to be useful for progressive surgical treatment of Kawasaki disease. PMID- 1405158 TI - [Adult respiratory distress syndrome]. PMID- 1405159 TI - [Techniques and problems of blood purification]. PMID- 1405160 TI - [Urodynamic findings in patients with a urethral Kock pouch after radical cystectomy]. AB - Urodynamic evaluation was performed in 11 male patients, who underwent radical cystectomy with pelvic lymph node dissection for bladder cancer followed by bladder replacement with a urethral Kock pouch, 3 to 21 months after the operation. Frequency of micturition were 4.9 +/- 1.5 times (mean +/- S.D.) during the day-time and 1.5 +/- 1.2 times during the night-time. Tidal volume of micturition ranged from 300 to 550 ml and residual volume from 10 to 30 ml. Urinary continence was completely preserved in all patients (100%) during the day time and 8 (72.7%) during the night-time. On pouchmetry, maximum capacity of the pouch was 429.2 +/- 82.4 ml, and intra-pouch pressure was 16.2 +/- 5.4 cmH2O at the capacity of 200 ml and 38.7 +/- 11.5 cmH2O at the maximum capacity. Maximum intra-pouch pressure on voiding was 80.0 +/- 19.4 cmH2O. Uroflowmetry demonstrated intermittent voiding curves in all the patients, with maximum flow rate of 15.2 +/- 6.5 ml/sec, voided volume of 405.9 +/- 80.7 ml and residual rate of 4.5 +/- 2.6%. Maximum intra-urethral pressure at the external urethral sphincter was 28.0 +/- 11.3 cmH2O when the pouch was empty and increased in response to pouch filling up to 64.7 +/- 27.0 cmH2O. Maximum urethral closing pressure and total profile length on the urethral pressure profile were 30.2 +/- 12.4 cmH2O and 20.9 +/- 9.0 mm, respectively, with the pouch empty, and 23.2 +/- 14.5 cmH2O and 20.0 +/- 7.6 mm, respectively, with the pouch full.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405161 TI - [The clinical significance of tissue, blood and urine polyamine in renal cell carcinoma]. AB - With the use of a newly developed and convenient enzymatic method, tissue, urine and blood polyamine (diamine, spermidine and spermine) levels were evaluated as a tumor marker of renal cell carcinoma (RCC) in 50 cases with the disease. Furthermore, blood and urine polyamines were periodically determined and evaluated as a follow-up marker. The pretreatment three polyamine levels in tissue, blood and urine of the patients were all significantly higher than those of the controls. However, because of their low sensitivities, they were not always decisive for biochemical diagnosis of RCC. Tissue spermidine levels were increased with the advance of the stages. Tissue diamine level also showed a good correlation with the pathological grade. Tissue diamine was found to predict distant metastasis. Blood spermidine and urine diamine were useful as follow-up markers. In conclusion, combined determination of tissue, blood and urine polyamine levels was thought to be useful as tumor markers of RCC. PMID- 1405162 TI - [Results of curative or non-curative nephrectomy for renal cell carcinoma invading adjacent organs]. AB - We reviewed 12 patients who had undergone curative or non-curative nephrectomy for renal cell carcinoma invading adjacent organs (stage T4). 83 patients with renal cell carcinoma confined within the perirenal fascia (T1-T3) who had undergone nephrectomy served as controls. Of the 12 patients with T4 tumor 6 had undergone simultaneous excision of involved adjacent organs (hemicolectomy in 4, resection of the tail of pancreas in 5, splenectomy in 2). At operation 6 patients with T4 tumor had distant metastasis, 3 had fixed lymph node metastases, and 4 had tumor extension into the main renal vein or vena cava. Although T4 tumor had distant or fixed lymph node metastasis more frequently than T1-T3 tumors, the incidence of gross tumor thrombus showed no such difference between T3 and T4 tumors. Postoperative follow-up of patients with T4 tumor showed that local recurrence developed within 9 months in 3 of 5 patients who had undergone curative excision, new distant metastasis developed within 6 months in 5 patients, 1 patient died of acute renal failure in the early convalescence, 10 patients died of the disease within 12 months and 1 died of the disease in 31 months. Pathological examination showed that T4 tumors tended to be classified as grade 3, to extend in an infiltrating fashion and to have a sarcomatoid structure. Patients who had a tumor where these three histological features were dominant died to tumor within 3 months after nephrectomy. These results indicate that curative excision of T4 renal cell carcinoma is not only difficult, but frequently associated with early local recurrence and new distant metastasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405163 TI - [Clinical studies of the prognosis in cases of chance proteinuria and/or hematuria]. AB - A total of 174 cases that consulted due to chance proteinuria and/or hematuria (CPH) were studied as to its clinical course, in particular patients' prognosis. They were selected from 311 patients on whom renal biopsy was performed from December, 1975 to December, 1985 in our institute. Furthermore, IgA nephropathy which occupied the major part of the CPH group was also studied as a prognostic factor. The CPH group showed 81% of disease stabilizing rate in 10 years' follow up. In various data such as chemical analysis of blood and urine, immunoglobulin levels, and renal function at the time of biopsy, daily urinary protein excretion (greater than 1 g/day) statistically showed a significant correlation to deterioration of the renal function during the follow up. However, hematuria was not found correlated. Of CPH group, 48% was diagnosed to be with IgA nephropathy. The patients with IgA nephropathy with CPH, comparing with the cases without CPH, were younger and had better renal function and milder change of renal mesangial proliferation. The 10 years-disease stabilizing rates of the disease were 81% in CPH and 63% in non CHP group. In conclusion, prognostic factors affecting renal function in the CPH group was found to be daily urinary protein excretion and, if diagnosed as IgA nephropathy by biopsy, pathological changes were also shown to be prognostic factors. Therefore, CPH patients having proteinuria over 1 g/day must be examined by renal biopsy and when IgA nephropathy is diagnosed, long time follow-up is necessary and re-biopsy for examination of pathological change during the interval is recommended. PMID- 1405164 TI - [Purification and properties of NAG A from human kidney]. AB - In the present paper, we have reported the purification procedures of N-acetyl beta, D-glucosaminidase (NAG) A from human renal tissue as well as the enzymatic properties of NAG A. NAG A was purified to homogeneity by gel filtration methods using Sephacry S-400 and S-200, followed by affinity chromatography with TSK DEAE 5-PW. The final activity of the enzyme was 1001 U/ml protein which was 506.6-fold that of the crude extract (supernatant of 20,000 x G of the homogenate). The molecular weight of NAG A was 140 kDa, consisting of two subunits of 30 kDa and 57 kDa. The isoelectric point of the enzyme was 5.60. The optimal pH of the enzyme was between 4.7 and 4.9. The Km value of the enzyme for sodio-m-cresol sulfophtaleinyl-N-acetyl-beta, D-glucosaminide was found 0.177 x 10(-3) mol/l. Lectin affinity chromatographies using concanavalin A and wheat germagglutinin have demonstrated that major sugar-chains of the enzyme were the high mannose type and hybrid type with a fucose residue, and that a small amount of the complex type was contained. PMID- 1405165 TI - [Prognostic factors for progression of superficial bladder cancer]. AB - To clarify prognostic factors for progression of superficial transitional cell carcinoma of the bladder (Ta, T1 and G1, G2), 159 patients, treated by transurethral resection from 1975 to 1988, were analysed concerning clinical findings, laboratory data, endoscopic findings and histopathological findings of the tumor. Histopathological findings included ABH blood group isoantigen (ABH) and Thomsen-Friedenreich antigen (T-ag) as well as other result. Twenty two cases in the series showed progression; 10 with up-grading and up-staging, 12 with either one of them. Advanced age, positive urinary cytology, multiple or broad base tumor, G2 or T1 tumor, negative ABH and abnormal T-ag were closely associated with progression. By multivariate analysis of these factors, ABH, stage of the tumor, T-ag and form were shown to be important prognostic factors in this order. ABH and T-ag were not correlated with other clinicopathological factors in predicting tumor progression. Therefore we concluded that ABH and T-ag were much important for prediction concerning potential for progression of the superficial bladder cancer. PMID- 1405166 TI - [Asymptomatic multilocular cystic renal cell carcinoma]. AB - From January 1982 to December 1989, we experienced seven multilocular cystic renal cell carcinomas (MLCRCCs) in 36 asymptomatic renal cancers incidentally diagnosed, and none in 23 symptomatic renal cancers (p less than 0.05). No multiocular cystic nephromas (MLCNs) appeared in either group. Though MLCRCCs have been considered to be, in general, extremely rare, they do occur in asymptomatic renal cancers. A multiloculated renal mass with thick septum discovered in an adult by ultrasonography or CT scan should be suspected as being a MLCRCC rather than a MLCN. PMID- 1405167 TI - [Results of deep dorsal vein ligation for venogenic impotence]. AB - We treated seventy venogenic impotence with ligation of the deep dorsal vein of the penis. Their corporal veno-occlusive function was evaluated by dynamic infusion cavernosometry and cavernosography (DICC). Under local anesthesia, we made a longitudinal skin incision at the base of the penis. The deep dorsal vein was ligated and also a portion of this vein of 1.5 cm long was resected together with branches surrounding the vein. After the operation, the infusion rate determined by DICC was confirmed to be decreased in almost all patients. Thirty nine out of seventy cases had their erectile capability restored and reported that they could achieve sexual intercourse. Sixty one of the seventy cases showed full erection together with an intracavernous papaverine injection. However fifty percent of the sixty one patients who became capable of obtaining erection with the treatment had lost their erectile capability again within one year of the operation, however the other fifty percent were shown to maintain their erectile capability for up to three years. As four years after the treatment only thirty percent of those who had achieved the initial erectile capability still remained potent. This operation is easy to perform without any major complications, and its outcome is as good as that achieved by other more invasive venous ligation in the treatment of patients with venogenic impotence. We therefore conclude that penile deep dorsal vein ligation and partial resection of the vein one of the most useful treatments currently available for venogenic impotence and should be the treatment of choice. PMID- 1405168 TI - [A survey on urinary incontinence in the institutionalized elderly]. AB - A survey on urinary incontinence in 161 (41 male, 120 female) institutionalized elderly was independently performed by urologists and attending nurses. Urinary incontinence was found in 107 cases (66%), with 76 cases (47%) suffering from severe leakage (more than 5 times a day and needs diaper). The prevalences of incontinence and severe leakage were 63% and 52% at geriatric hospitals, 59% and 29% at intermediate care centers and 78% and 63% at nursing homes, respectively. The risk factors for incontinence were consciousness disturbance, urinary urgency, impaired mobility and dementia, and those for severe leakage were apathy, loss of urinary sensation, dementia and impaired mobility. The type of incontinence was considered functional one in 81% of cases. The agreement of the incontinence type evaluated by urologists and that by nurses was found in 90% of incontinent cases. Incontinence was estimated "incurable" in 54% of cases by attending nurses. These observations indicate a high prevalence of severe and "incurable" incontinence in the institutionalized elderly, urgently warranting an effective remedy for the increasing aged society. PMID- 1405169 TI - [Electromyographic study on the striated urethral sphincter of the male. An analysis with turns amplitude diagram]. AB - The aim of this study is to clarify the physiology and pathophysiology of two striated urethral sphincters, the periurethral striated sphincter (PUS) and the external urethral sphincter (EUS), in the voiding cycle, using a selective and semi-quantitative electromyographic technique. Under ultrasonic guidance, two needle-electrodes were inserted into the two sphincters of 31 males (7 neurologically normal, 13 with nuclear and/or infranuclear lesions, 11 with supranuclear lesions), and EMGs recorded during the whole cystometric course were analysed by the aid of Turns-Amplitude Diagram (TAD). The results obtained were as follows: 1) In neurologically normal cases, the increment of turns as well as amplitudes in EMGs of both the sphincters were observed with the bladder filling, and they were completely diminished at the onset of than voiding. 2) The increment of turns were more obvious than that of amplitudes in EMGs of both the sphincters. 3) More voluntary function could be assumed on EUS than PUS. 4) The functional sphincteric responsibility corresponding to the voiding cycle could be expressed by the direction and the length of the vectors obtained from TAD. 5) In neurogenic bladder cases, various abnormal sphincteric responsibility, such as the shortening and/or abnormal directions of the vectors, were found. With the results described above, this semi-quantitative assessment of sphincter EMG was thought to be useful to evaluate the abnormal activity of the urethral sphincter in neurogenic bladder cases. PMID- 1405170 TI - [Prophylactic intravesical instillation therapy in patients with superficial bladder cancer--results of a randomized prospective study]. AB - A randomized prospective study was conducted for the purpose of investigating the efficacy of intravesical chemoprophylaxis of superficial bladder cancers. Eligible patients were randomized into three groups: 1) adriamycin (ADM) group; intravesical instillation with 50 mg of ADM dissolved in 100 ml physiological saline, 2) mitomycin C (MMC) group; intravesical instillation with 30 mg of MMC dissolved in 100 ml of physiological saline, 3) control group; transurethral resection or transurethral coagulation only. The characteristic features of our protocol consisted of frequent (six times) instillations of the drugs within two weeks after transurethral resection, followed by instillations on two consecutive days at four-week intervals for two years. Furthermore, large quantities (100 ml) of instillation fluid containing relatively low concentrations of the drugs (500 micrograms/ml for ADM or 300 micrograms/ml for MMC) were employed. One hundred and forty-four patients have been submitted to the study; 110 patients were fully evaluable for recurrence and 34 patients were eliminated as non-evaluable patients. The cumulative five-year non-recurrence rates of the patients with multiple tumors were 32% in the MMC group, 25% in the ADM group and 7% in the control group. The cumulative non-recurrence rates of the ADM and MMC groups were significantly higher than that of the control group. It is considered that this instillation therapy with ADM and MMC is useful for preventing the recurrence of superficial bladder cancers. PMID- 1405171 TI - [Primary tumor of the ureteral stump following nephrectomy for non-malignant disease. A case report]. AB - Primary tumor in the ureteral stump is rare. A 66-year-old woman visited our hospital because of microscopic hematuria. She had undergone right nephrectomy for the contracted kidney 36 years ago. Intravenous pyelography and cystoscopy showed no positive findings for hematuria. But urine cytology indicated class V. The flexible ureterorenoscopy disclosed a nonpapillary sessile tumor in the ureteral stump. We also did the biopsy of the tumor under the direct vision before open surgery. The specimen showed transitional cell carcinoma, grade 3. The ureteral stump was successfully removed. The flexible ureterorenoscopy was most useful for the diagnosis in this case. PMID- 1405172 TI - [A case of scrotal bladder hernia containing bladder cancer]. AB - A 70-year-old man had a history of total laryngectomy for laryngeal cancer and bilateral inguinal hernia repair 5 years previously. The patient had suffered from difficulty with urination since then and had been treated for prostatic hypertrophy at our department. He developed microscopic hematuria from June 1991, and was admitted because a bladder tumor was detected by cystoscopy. Cystography showed a scrotal bladder hernia with filling defects in the bladder per se and the bladder hernia as well. Cystoscopy revealed tumors in the hernia and in the vicinity of the ureteral orifice. Biopsy indicated transitional cell carcinoma. Voiding cystourethrography showed normal urination and no residual urine. Excision of the tumor-containing hernia, partial cystectomy with right ureteral orifice, and reconstruction of the right inguinal canal were performed on October 25, 1991. The postoperative course was favorable and he was discharged on the 40th postoperative day. The tumors were respectively stage as TCC, G1, and pT1a, and TCC, G1 greater than G2, and pT1b. Thirty five cases of bladder hernia that have been reported in Japan. Eight cases of accompanied by cancer have been reported in Japanese (3 cases) and foreign (5 cases) literatures. These are reviewed and discussed. PMID- 1405173 TI - Art for art's sake. PMID- 1405174 TI - Medicine and business: traveling on the same road. PMID- 1405175 TI - COBRA and emergency room care (revisited). PMID- 1405176 TI - Ron Todd: a stern regulator with a low-key style. PMID- 1405177 TI - Education sessions cover AIDS, health insurance reform and RBRVS. PMID- 1405179 TI - AIDS in Kansas, 1981-91. PMID- 1405178 TI - The high-risk register for hearing loss in Kansas: some preliminary data. PMID- 1405180 TI - Tobacco--its use and abuse. 1925. PMID- 1405181 TI - Identifying systolic murmurs at the bedside. PMID- 1405182 TI - Tuberculin survey in Ethiopia. AB - For planning and implementation of effective national tuberculosis control programme (NTP) in Ethiopia, it is essential to know the real magnitude of tuberculosis problem. Previous tuberculin survey carried out during the period from 1953 to 1955 revealed the annual risk of infection 3.0%, and since then, there has been no survey. A new tuberculin survey was thus conducted during the period from December 1987 to April 1990. In order to get a sample of 47 previously BCG unvaccinated children, aged 6 to 10 years, selected from each 480 representative clusters of randomly selected 16 Woredas (districts), a total of 26,529 children, approximately 55 in each cluster, were given tuberculin intradermal injection, and the reaction was read in 26,269 children (99.0%). A scar survey was done, and 23,695 had no BCG scar, while 2,574 (10.1%) had BCG scar. Out of the former, 2,503 children (10.6%) were positive, and the annual risk of infection thus calculated was 1.4%. Out of the latter, 591 (23.0%) were positive. The results of these two surveys indicate that tuberculosis showed decline in the past 37 years with the annual reduction rate of 2.2%, however, the trend might change in the future due to present pandemic of HIV infection. PMID- 1405183 TI - [The study of pulmonary tuberculosis in the elderly]. AB - A clinical study of 52 patients diagnosed as having pulmonary tuberculosis at National Chiba-Higashi Hospital between 1988 and 1990 was performed. The cases ranged in age from 80-89 years; mean male patient age was 82.5, and mean female patient age was 84.3. Diagnosis of the cases were as follows: 19 discovered when checking into hospital because of chest symptoms; 14 diagnosed during the treatment of other diseases; 14 diagnosed during admission to the hospital for other diseases; and five cases were detected by chest X-rays. A total of 38 cases, had received primary treatment for pulmonary tuberculosis, 11 cases had received secondary treatment, and three cases were receiving treatment for tuberculosis. Upon admission to the hospital after the detection of tuberculosis, 19 cases tested positive to sputum smear examinations, six cases tested positive to culture examinations but negative to smear examinations, and culture examinations were negative in 27 cases. Regarding the chest X-ray findings, using the criterion of roentgenological classification for pulmonary tuberculosis established by the Japanese Society for Tuberculosis, two cases revealed type I, 29 cases revealed type II, and 21 cases revealed type III. Cavitary cases were observed in 60% of the chest X-ray findings. Upon hospital admission, 18 cases were observed to have circulatory diseases, 16 cases had central nervous diseases, 12 cases had digestive diseases and 11 cases had respiratory diseases. Nine cases had malignant neoplasm, five cases had diabetes mellitus and 14 cases had other diseases. A total of 18 cases ended in death; six cases died of pulmonary tuberculosis, and 12 cases died of other diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405184 TI - [A case of inflammatory bronchial polyp associated with pulmonary and bronchial tuberculosis]. AB - A 67-year-old man was admitted to our hospital because of cough and sputum. Chest X-ray revealed cavity and consolidation in the right upper lobe. Microscopical examination of stained specimens of sputum disclosed acid-fast bacilli (Mycobacterium tuberculosis). Cough and sputum resolved and cultures of sputum did not yield M. tuberculosis a month after administration of antituberculosis agents. However, a mass shadow in the right upper lobe was found 3 months later. Bronchofiberscopy revealed a polyp with a stalk at the orifice of right upper bronchus, which was elastic, soft in consistency, smooth surfaced, and movable. The pathological findings of the polyp showed non-specific inflammatory granulation which suggested to be inflammatory bronchial polyp. It was appeared in the healing process of bronchial tuberculosis. PMID- 1405185 TI - [Short course chemotherapy and relapse in pulmonary tuberculosis in Japan]. AB - As far as short course chemotherapy of pulmonary tuberculosis is concerned, Japan is considered to have been a little behind the trend of the world in the past. However, since 1978 the concept of the chemotherapy has begun to be adopted in some hospitals and research councils (Cooperative Study Unit of Chemotherapy of Tuberculosis of National Sanatoria, Tuberculosis Research Committees, Ryoken), and then seems to be prevailing in other hospitals as the results of their gradual understanding. This movement has likely been accelerated since Dr. W. Fox came to Japan in 1978 at the invitation of Japanese Society of Tuberculosis and gave us much information and suggestion through his special lecture on short course chemotherapy of tuberculosis. Fifteen years have past since short course chemotherapy started in Japan. At this opportunity, I would like to review the results of short course chemotherapy studies reported by Japanese investigators. Bacteriological relapse rates in cases followed-up for three years and for from five to nine years after the end of short course chemotherapy were 1.9% (20 out of 1067) and 3.3% (26 out of 783), respectively. According to the analysis of the time of relapse after completion chemotherapy, bacteriological relapses could be divided into two types. One was early relapse which occurred within one year after completing treatment, and the other was late relapse which occurred two or three years after completing treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405186 TI - [Elimination of tuberculosis in Japan]. AB - According to the operational definition adopted at Wolfheze Workshop held in March 1991 (Table 1), tuberculosis low incidence countries are defined as those where the incidence of all forms of tuberculosis is less than 1 per 100,000. The incidence was 41.9 in 1990 in Japan, so that Japan cannot be considered as a low incidence country. Why is the incidence of tuberculosis so high in Japan? What part of population is affected by the tuberculosis disease? To solve these questions and to make clear the mode of development of tuberculosis, a study was carried out. Fortunately, both the annual risk of tuberculosis infection and the prevalences of persons with healed and/or fibrotic lesion in the lung are known from the results of the National Tuberculosis Prevalence Surveys carried out in 1963 and 1973 as shown in Figures 1 and 2. From these data, the number of newly infected within 5 years and that of remote infections by age group were estimated. The former was divided into BCG vaccinated and non-vaccinated and the latter into persons with fibrotic lesion, with healed foci and without abnormality in the lung. (Table 2). The rates of development of tuberculosis disease according to the X-ray findings of the lung were observed at the five years follow-up study of all the examinees at the Prevalence Survey carried out in 1968. The ratio of development of the disease in those with recent infections, remote infections with fibrotic lesion, those with healed foci and those without abnormality was estimated as 20 : 10 : 2 : 1. (Table 3)(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405187 TI - Special consideration: rural health care delivery. PMID- 1405188 TI - Rural nursing centers: are they a reality? PMID- 1405190 TI - Restructuring health care systems with nurse practitioners in rural western Kansas: a feasibility study. PMID- 1405189 TI - One rural hospital's innovative maternity staffing pattern. PMID- 1405191 TI - Keeping up: literature resources available to nurses in Kansas. PMID- 1405192 TI - [Early results of surgical treatment of patients with Wolff-Parkinson-White syndrome]. AB - Successful dissection of accessory pathways (AcP's) was performed in 19 of 20 patients. 15 pts had single, 4 double and 1 patient had 3 accessory pathways (AcP's). The patient with 3 AcP's was operated twice. During the first operation two AcP's were eliminated. The third one was revealed during the postoperative electrophysiologic study. Verapamil facilitated its manifestation and localisation. No patient had syncope or atrio-ventricular tachycardia after the operation. In 3 of 10 patients who had atrial fibrillation before the operation, episodes of AF occurred in the early postoperative period. Conduction to the ventricles was through the normal conduction system. Dissection of AcP's prevented extremely fast ventricular response and syncope. After discontinuation of amiodarone more frequent ventricular premature beats occurred in patients with long history of cardiac arrhythmias, on drugs for a long time and in patients who had heart dilatation. Several months after the operation VEB were less frequent, probably because tachycardias did not occur, left ventricle geometry improved, and cardiodepressant drugs were discontinued. Previously these patients had been treated usually with combination of 2-3 such drugs. After the successful dissection of AcP's the patients lost the feeling of illness and do not feel being imperilled. Children can attend schools normally and some adult patients resumed their professional activities. PMID- 1405193 TI - [A case of perforation of the pericardial sac by Seldinger's catheter guide]. AB - This is a case report of perforation by Seldinger's catheter leader into pericardial sack. The leader was inserted contrary-wise++ to the subclavian vein with the sharp end in front. The leader moved forward toward the venous system and perforated into the pericardial sack. The preceding steroid therapy which the patient had undergone due to asthmatic status resulted in mediastinitis after the primary surgery. Right technique of reoperation and intensive postoperative care led to patient recovery. PMID- 1405194 TI - [Left coronary artery-pulmonary artery fistula. Case report]. AB - A case of a 45-year-old male with anterior descending branch of the left coronary artery fistula to the main pulmonary trunk is reported. The patient was admitted because of a retrosternal pain. ECG showed ST-elevation in leads V2-3. This was first episode of anginal symptoms. The authors suggest that the single episode of coronary pain may have been provoked by faintness (following alcohol consumption) in the mechanism of the steal syndrome or by coronary spasm. A fistula (on coronarography) was diagnosed (the coronary arteries showed no changes). The value of the shunt calculated via Flick's method was 1.1 l/min. Exercise test, 24 hour ECG recording as well as stress thallium scintigraphy did not reveal post exertion ischemic changes. During a 17-month post hospitalization follow-up the patient reported no anginal symptoms. Because of the small shunt and asymptomatic follow-up no surgical treatment was recommended. PMID- 1405195 TI - [Non-pharmacological methods of the treatment of arrhythmia]. PMID- 1405196 TI - [Enalapril improves hemodynamics and exercise tolerance in pulmonary heart disease caused by obstructive lung disease]. AB - Chronic enalapril therapy was assessed in 11 patients with cor pulmonale due to chronic obstructive pulmonary disease. Enalapril was added to the maintenance dose of diuretics and digitalis and when clinical stabilisation was achieved haemodynamics, spirometry, blood gases and maximal treadmill exercise test accompanied by +pulse oximetry were performed before and after 30 days, 10-20 mg a day, enalapril therapy. Haemodynamic study showed moderate but significant decrease in mean pulmonary artery pressure, from 24 +/- 3 to 21 +/- 5 mmHg (p = 0.05). There were no substantial differences in cardiac output as well as in blood gases and spirometry after enalapril therapy. Slight decrease in oxygen delivery, on an average from 9157 +/- 3808 to 8074 +/- 3574 (p = NS), was accompanied by a concomitant fall in haemoglobin. We noted significant improvement of maximal exercise test results after enalapril therapy. Maximal workload achieved and the time of exercise increased. It was accompanied by subjective improvement as assessed by Borg scale. We observed no adverse effects of enalapril during one month therapy in patients with cor pulmonale and COPD. PMID- 1405197 TI - [The minimum one should know about percutaneous arterial angioplasty]. PMID- 1405198 TI - [Is atherectomy an alternative to coronary angioplasty in ischemic heart disease?]. PMID- 1405199 TI - [Effect of ventricular and sequential stimulation on the left- ventricular systolic function]. AB - Left ventricular systolic function at rest was determined by echocardiography and Doppler in 20 patients after dual chamber pacemaker implantation due to second and third degree A-V block. Measurements were performed in each patient during VVI and DDD mode pacing at three different atrio-ventricular (A-V) intervals: 100, 150 and 200 ms. The essential hemodynamic superiority of DDD stimulation over VVI mode in the form of significant increase of forward stroke volume index (SVI) and cardiac index (CI) during dual chamber stimulation at identical rate stimulation was observed. Closer individual analysis of the values of CI during DDD stimulation at three different A-V intervals (100, 150 and 200 ms) gave the possibility of programming optimal A-V intervals (the highest value of CI) for each patient. The sequential atrio-ventricular stimulation as compared to right ventricular stimulation essentially improves the left ventricular systolic function at rest in patients without symptoms of heart failure. Maximum hemodynamic advantage during DDD stimulation depends on individual selection of A V delay in each patient. PMID- 1405200 TI - [Calcium antagonists in the treatment of heart failure in patients with myocardial infarction. Experience with clinical use of intravenous dilcem (diltiazem)]. PMID- 1405201 TI - [Plasma beta-endorphin level in "silent" myocardial ischemia during Holter ECG monitoring]. AB - The results from recent studies suggest that the endogenous opioid beta-endorphin (beta-E) is related to pain modulation. Therefore, plasma beta-E levels were studied in 23 patients with essential hypertension (EH) and in 7 patients with coronary artery disease (CAD) during asymptomatic ischemic events and in 5 patients with CAD during symptomatic ischemic events. Blood samples for beta-E were taken at the moment of silent ST depression, pointed with alarm by the real time ECG monitor "Q Med Monitor" (USA). Control blood samples were taken under the same conditions without ischemic events. Control plasma beta-E levels were significantly higher (p less than 0.01) in patients with EH as compared to that in both groups of patients with CAD (22.9 +/- 4.0 vs 7.0 +/- 1.9 and 4.5 +/- 1.6 pmol/l). At the time of silent ischemia, beta-E showed a significant increase in patients with EH (+10.1 +/- 2.1 pmol/l, p less than 0.01) and in patients with CAD (+10.7 +/- 1.3 pmol/l, p less than 0.05) as compared to the control levels. However, plasma beta-E showed no increase (+1.0 +/- 0.6 pmol/l, p greater than 0.1) during symptomatic ischemia as compared to the control levels. Thus, differences in the circulating levels of beta-E may be associated with the presence or absence of pain during myocardial ischemia. PMID- 1405202 TI - [Clinico-genealogical characteristics of patients with ischemic heart disease and different disorders of lipid metabolism]. AB - The paper presents a clinical and genealogical characterization of 50 probands suffering from coronary heart disease concurrent with various lipid metabolic disturbances and 211 first-degree relatives whose data have been obtained from the probands' histories while making up their pedigrees. The prevalence of atherosclerosis among the first-degree relatives has been demonstrated to be related to the nature of lipid metabolic disturbances in a proband. Some dyslipoproteinemias in the proband have been characterized by early onset of coronary heart disease, stroke, and their grave course in close relatives. PMID- 1405203 TI - [Effect of the tourniquet test on fibrinolysis, thrombocytic hemostasis and the antithrombin III system in ischemic heart disease and exercise-induced stenocardia of the III-IV functional classes]. PMID- 1405204 TI - [Effect of psycho-emotional stress test on the blood coagulation system and thrombocytic hemostasis in patients with stenocardia]. AB - A total of 101 male patients (mean age 52.3 +/- 1.7 years) with documented coronary heart disease and stable angina and 25 healthy males (mean age 49.8 +/- 2.0 years) were studied. Hemostatic parameters and catecholamine levels were determined at rest, at the peak of psychoemotional stress test and at 10 min of rest. During the test, the healthy subjects showed a protective activation of the anticoagulative hemostatic system that hindered intravascular blood coagulation. Some definite compensatory potentials of the blood anticoagulative system preserved in Type B behavior patients under the similar conditions. The patients with Type A behavior displayed enhanced intravascular coagulation and increased thrombogenic potential. PMID- 1405205 TI - [Substantiation of safe conducting of early bicycle ergometry in patients with myocardial infarct]. PMID- 1405206 TI - [Comparative evaluation of cardiovascular function in patients after myocardial infarction during exercise test with the optimal and sub-optimal frequency of pedalling]. AB - Cardiovascular function was studied in 59 patients with myocardial infarction during their bicycle ergometer exercise performance at optimal and +sub-optimal pedalling rates. The total performance at the optimal rate was found to average 1.48 times more than that at the +sub-optimal rate. The efficiency of cardiovascular performance was achieved by a less increase in heart rate and systolic pressure. ECG changes resulting in exercise test cessation were observed in 7 and 30 cases at the optimal and +sub-optimal rates, respectively. It is concluded that physical training that fails to impose patients' rhythm and exercise capacity are more physiological and maximally safe. PMID- 1405207 TI - [Effect of corinfar on hemodynamic indicators and clinical manifestations in patients with ischemic heart disease and stenocardia during psycho-emotional stress]. PMID- 1405208 TI - [Crystallogenic properties of serum lipid fraction in healthy persons and in patients with ischemic heart disease]. AB - A crystallization method was proposed to assess disturbances in the lipid system; it was based on the interaction of a serum lipid fraction with a lecithin matrix. A total of 255 invidividuals were examined. A model experiment was performed by using chemically pure cholesterol (96 samples) and 10 different cholesterol esters (240 samples). There were a great differences in the frequency of various pattern structural types (homogeneous texture, fan crystals) in the healthy persons and patients. The test results were found to be related to the ratio of esterified to non-esterified cholesterol in the serum lipid fraction. The application of rheopolyglucin, , hemosorption, quantum hemotherapy in the patients contributed to normalization of crystallization test indices. PMID- 1405209 TI - [Effect of long-term treatment with prazosin and its combination with nadolol on the levels of blood hormones of the hypophyseal- gonadal system in patients with hypertension]. AB - The levels of pituitary and gonadal hormones were measured by radioimmunoassay during a long-term (12-month) therapy with prazosin and its combination in 23 patients aged 30-59 years who suffered from Stage II hypertensive disease. Prazosin monotherapy resulted in a significant decrease in prolactin levels, followed by inhibited elaboration of luteinizing, follicle-stimulating, and testicular hormones in the first 6 months of therapy without changing estradiol levels. The hypoprolactinemic effect of prazosin was significantly enhanced with an increase in therapy duration and more profound in patients who had high baseline prolactin levels and in younger patients. Prazosin in combination with nadolol was found to level off the hyperprolactinemic effect of the latter without potentiating the reduction in the levels of follicle-stimulating, luteinizing, and testicular hormones which was observed during therapy with each drug alone. PMID- 1405210 TI - [Study of myocardial perfusion in patients with hypertension]. AB - Exercise 199Tl myocardial scintigraphic data were studied during dipyridamole test in 39 patients with Class II essential hypertension. Transient myocardial perfusion defects were revealed in 60% of patients with negative exercise test. Intraventricular administration of albumin microspheres in 8 females with normal coronary artery allowed the authors to detect areas of their accumulation at the same sites as in exercise 199Tl myocardial scintigraphy. Thus, the changes in the small vessels which are revealed by intraventricular albumin microspheres are one of the causes of impaired myocardial perfusion in patients with essential hypertension. PMID- 1405211 TI - [Peroxidation of membrane lipids and the antioxidant levels at various stages of development of "hypertensive" heart]. PMID- 1405212 TI - [Changes in the activity of antioxidant enzymes in patients with hypertension]. AB - The authors examined the activity of the antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GP) in the blood of patients with permanent essential hypertension and hypertensive crises and changes in the activity of these enzymes when monotherapy with the calcium antagonist corinfar was used. A total of 62 patients (age 52.7 +/- 0.7 years) with hypertension and 25 apparently healthy volunteers (age 43.9 +/- 0.7 years) were examined. The activity of SOD and GP was found to be decreased by 33 and 22%, respectively, in patients with permanent hypertension and by 40 and 32%, respectively, during hypertensive crises. When hypertension was treated with corinfar, the activity of COD and GP was increased by 10 and 18%, respectively. Concurrently, these patients had subjective and clinical improvement. The findings suggest that impaired lipid peroxidation makes a great contribution to the pathogenesis of essential hypertension. It can be assumed that the use of antihypertensive agents producing effects on the level of lipid peroxidation products and the enhancements of the activity of antioxidative enzymes. PMID- 1405213 TI - [Surgical treatment of unstable stenocardia]. PMID- 1405214 TI - [Current methods of mathematical analysis of cardiac rhythm]. PMID- 1405215 TI - [Limitation of adrenergic cardiovascular damage by exogenous infusion of a regulatory peptide dalargin]. PMID- 1405216 TI - [Changes in myocardial contractility and the myocardial microcirculatory bed in the post-ischemic period in relation to the degree of its hypothermic protection]. PMID- 1405217 TI - [The role of the prostaglandin system in the cardioprotective effect of adaptation to hypoxia in stress]. AB - The adaptation to periodic altitude hypoxia is known to have cardioprotective and antiarrhythmic effects in stress-induced and ischemic lesions. The effects are assumed to be associated with the enhanced activity of the body's stress-limiting systems, including prostaglandins (PG). Wistar rats were adapted in a hypobaric chamber at an altitude of 4000 m for 6 hours during 40 days. The levels of myocardial and plasma PGE, PGE2 alpha, PGI2, thromboxane A2 were measured by radioimmunoassay and those of plasma catecholamines by enzyme radioassay. In the myocardium, the adaptation showed a 2-fold increase in PGE levels, the PGE/PGE2 alpha ratio and PGI2 levels rose by 70 and 73%, respectively, the PGI2/thromboxane A2 ratio remaining unchanged, while thromboxane A2 concentrations also rose. In adaptation, the levels of PGE and PGI2 was 78 and 60% higher, respectively. In restraint stress, myocardial and plasma PG levels proved to be substantially higher in adapted animals than in the controls, but stress-induced plasma catecholamine release, i.e. stress reaction, showed a 2-3 fold decrease that in the controls undergoing the same stress. The findings along with the data on the cytoprotective and vasodilating action of PGE and PGI2 suggest that enhanced activity of the myocardial and blood PG system is the important link in the mechanism responsible for the antistress impact of adaptation. PMID- 1405218 TI - [Prostacyclin-thromboxane imbalance after adrenergic damage of the heart and aorta and its correction with calcium antagonist finoptin and the adaptation to high-altitude climate]. AB - Adrenergic cardiac and aortic lesion was reproduced by using intramuscularly a stress-necrogenic epinephrine dose of 2 mg/kg. Following 24 hours, the levels of malonic dialdehyde (MDA) as a TxA2 marker, were measured in the platelets. The antiaggregability of the aortic wall where PGI2 is synthesized was also examined. The adrenergic lesion was found to impair the platelet function-vascular wall balance, creating the condition for enhancing spontaneous platelet aggregation. This led to 50% death of experimental "lowland" rats. The short-term high altitude adaptation failed to substantially modify the death rates in adrenergic lesion, though the platelets showed a 30% decrease in MDA generation. The combination of high-altitude adaptation and the calcium antagonist finoptin completely prevented the stress-induced increase in the platelet generation of MDA, a TxA2 marker, which was followed by a drastic reduction (16.6% versus 50%) in sudden death cases among the rats during adrenergic cardiac and aortic lesion. PMID- 1405219 TI - [Dynamics of myocardial function in the complex treatment of patients with heart failure using isolated ultrafiltration (polycardiographic data)]. AB - Sixty patients with Stages IIB-III chronic heart failure were examined. The main group included 30 patients on complex therapy involving isolated ultrafiltration (IUF), the other 30 patients who refused to have IUF comprised the control group. The patients from the main group had improvement in the phasic pattern of a cardiac cycle, which was associated with enhanced myocardial contractility and performance due to decreased preload. Improved phasic parameters observed after IUF sessions were sustained in the post-ultrafiltration period and different from those in the control group in which their significant changes were absent during treatment. PMID- 1405220 TI - [Comparison of the data of 24-hour ECG monitoring and the condition of the coronary bed in patients with the variants of the course of unstable stenocardia]. AB - A total of 232 patients with various clinical types of unstable angina pectoris were examined. All the patients underwent coronary angiographic studies, 24-hour ECG monitoring. In 40.5% of the patients, 24-hour monitoring revealed transient ST segment changes which were not accompanied by pain in 47% of the cases. ST segment changes were equally encountered in patients with one-, two-, and three vessel disease in the presence or absence of pain. Ischemic ST segment changes generally occurred with an anginal episode in patients with crescendo unstable angina, whereas in those with more prolonged and intensified pain and angina at rest in particular, silent myocardial ischemic episodes were significantly more frequently recorded, which were more common in these patients with multivessel disease. PMID- 1405221 TI - [Myocardial catecholamine levels in patients with congenital and acquired heart defects]. AB - Catecholamine levels were determined in the myocardial slices from 66 patients with congenital and acquired heart diseases by the trihydroxyindole++ method on a Lumilan fluorescence spectrophotometer. The patients were found to have greatly varying epinephrine and norepinephrine levels. The accumulation of catecholamine reflected, to a certain extent, the occurrence of disorders in relation to the functional load, hyperfunctions of the myocardium. Blood hypoxemia and myocardial hypoxia affected the status of the patients. PMID- 1405222 TI - [Pre-clinical ECG changes in patients with diabetes mellitus type 1]. PMID- 1405223 TI - [Potential possibilities of using adrenergic beta blockers in chronic heart failure]. AB - The study was undertaken to examine the efficacy of beta-adrenoblockers used in 26 patients with chronic heart failure which had been caused by coronary heart disease in 12 patients, by rheumatic heart disease in 8 patients, by dilated cardiomyopathy in 5 patients, and by chronic myocarditis in 1 patient. beta Blockers such as oxprenolol, propranolol, and metoprolol were supplemented to the therapy of the patients with chronic heart failure who were resistant to cardiac glycosides, diuretics, and vasodilators. This resulted in functional class improvement by the New York Heart Association from 3.67 +/- 0.1 to 2.29 +/- 0.1. The authors defined the following predictors of the efficacy of beta-blockers in chronic heart failure: duration of the disease, diastolic pressure, cardiac rhythm, and left ventricular ejection fraction and discussed the mechanisms responsible for their positive effect in chronic heart failure. PMID- 1405224 TI - [Quantitative characteristics of the structure of myocardial tissue studied by analyzing the integrated backscattering of ultrasound]. PMID- 1405225 TI - [Various aspects of the origin of the accent of the second cardiac sound]. PMID- 1405226 TI - [Effects of restored coronary circulation on nature and character of arrhythmia during attacks of angina pectoris in patients with ischemic heart disease]. AB - The nature and frequency of cardiac arrhythmias were studied in 23 patients with coronary heart disease during anginal episodes accompanied by ECG ST-segment depression and elevation. All the ischemic episodes were divided into 2 periods: (1) that from the onset of ST-segment displacement to its maximum; (2) that from the first period to the return of ST segment to the baseline position. The predictive poor ventricular arrhythmias were more frequently recorded in the second period of ST-segment displacement. The occurrence of arrhythmias was demonstrated to be related to the degree of ST-segment elevation (depression) and the duration of the first period of ischemic episode in the second period of ST segment displacement. PMID- 1405227 TI - [Dynamics of skin oxygen in patients with ischemic heart disease of the III-IV functional class under the effects of drug treatment]. PMID- 1405228 TI - [Study of left ventricular blood filling during post-pacing ischemia: comparison of Doppler echocardiography and heart catheterization]. AB - Left ventricular blood filling was performed in 72 patients by using pulsed Doppler echocardiography at rest and in postpacing ischemia. In 10 patients, non invasive examination findings were compared with the values of a left ventricular pressure curve which had been obtained in frequent atrial pacing. No changes in transmitral blood flow were found in patients without coronary heart disease, whereas 2 types of abnormal transmitral blood flow were detected in those with coronary heart disease in the postpacing period. The patients with Type I abnormal transmitral blood flow exhibited prolonged isovolumetric relaxation and slightly elevated left ventricular end-diastolic pressure in the postpacing period when catheterization was conducted. Those with Type I ("pseudonormal") transmitral blood flow displayed more prolonged relaxation and significantly (greater than 20 mm Hg) elevated end-diastolic pressure. The pattern of changes in transmitral blood flow was not pathognomonic to any definite myocardial abnormality, but reflected the hemodynamics. PMID- 1405229 TI - [Characteristics of bioelectric activity of brain structures in patients with different types of tachyarrhythmia]. AB - The paper gives the results of study of 81 patients with various paroxysmal tachyarrhythmias. All the patients underwent transesophageal pacing and electroencephalographic examinations. There was a relationship between EEG abnormalities and various tachyarrhythmias. PMID- 1405230 TI - [Effects of peripheral vasodilators on arrhythmia in patients with chronic coronary insufficiency]. PMID- 1405231 TI - [Effects of adaptation to periodic hypoxia on the course of idiopathic arrhythmia, microcirculation and blood coagulation]. PMID- 1405232 TI - [Anti-arrhythmia agents in heart failure]. PMID- 1405233 TI - [Anti-arrhythmia and hemodynamic effects of allapinin during a course therapy in patients with circulatory failure]. AB - The antiarrhythmic effects of allapinine were studied in 57 patients with chronic circulatory failure (CCF) and cardiac arrhythmias by employing 48-hour Holter monitoring. Allapinine was found to suppress premature ventricular contraction, group premature ventricular contraction and 'runs' of ventricular tachycardia by 82.5, 88.6, and 93.1%, respectively. The antiarrhythmic activity of the agent was more pronounced in patients with coronary heart disease, Stages I-IIA CCF and left ventricular ejection fraction greater than 40%. In addition, in Stages I-IIA CCF allapinine increased myocardial contractility and left ventricular ejection fraction, whereas in Stages IIB-III CCF it showed a slight cardiodepressive effect. Thus, when given in the course therapy in patients with CCF, allapinine has a high antiarrhythmic activity and, to a lesser extent, affects central hemodynamics. PMID- 1405234 TI - [Long-term treatment of hypertensive patients with captopril, enalapril and prazosin]. PMID- 1405235 TI - [A comparative analysis of 2 different approaches to implementing preventive measures in patients with borderline arterial hypertension]. AB - Routine recommendations were used to prevent hypertensive disease in patients with borderline arterial hypertension without using drugs in one of the surveys. The other involved the same methods under constant control and psychological maintenance to continue preventive measures. The second approach was found to be more effective and to considerably increase the patients' compliance. PMID- 1405236 TI - [Organization of prevention and treatment of arterial hypertension in women at industrial enterprises in Vladivostok]. PMID- 1405237 TI - [Immediate and long-term results of thrombolytic therapy in patients with myocardial infarct: the necessity of differential treatment]. AB - Systemic thrombolytic therapy was performed in 273 patients with large myocardial infarction: 82 on streptokinase, 25 on tissue plasminogen activator, and 166 on streptodecase. The signs of recovered coronary blood flow were observed in 68, 84, and 33% of the patients, respectively. The application of tissue plasminogen activator resulted in the maximum reperfusion. The success of thrombolytic therapy was related to the fibrinolytic system of a patient: reperfusion was achieved in 96% of patients having a high blood fibrinolytic activity and only in 31% with a low one. The clinical effect of reperfusion was most profound in patients with Killip's Class III heart failure. The patients with early recovery of coronary blood flow developed twice more frequently, which was evidenced by a 12-month follow-up. Fifty percent of patients with an ejection fraction of below 40% died within the first year of the follow-up. The authors discuss whether one can use a differential therapy, including surgical tools for myocardial revascularization. PMID- 1405238 TI - [Clinico-functional correlations of left atrial myocardial excursions in patients with mitral valve defects]. AB - The pre- and intraoperative drug maintenance was evaluated in 50 patients with mitral valvular disease and compared with the types of left atrial myocardial excursions. The maintenance with cardiac glycosides and diuretics was greatly different in 3 groups of patients with various types of left atrial myocardial excursions. In patients with Type I excursions the maintenance was minimal, in those with Type III excursions it was maximal, those with Type II excursions, it was intermediate. It is concluded that the functional characteristics of left atrial myocardial excursions may be used as an indicator of cardiac performance. PMID- 1405239 TI - [Features of blood lipid spectrum in a schoolchildren's population in Kharkov]. AB - The blood lipid and lipoprotein spectrum was biochemically studied in 580 pupils aged 12-16 years. The normal value ranges were found for total cholesterol (TC), triglycerides (T), high density lipoprotein (HDL) and low density lipoprotein in the Kharkov schoolchildren population. The upper limits of lipid lipoprotein levels enabled patients with hyperlipoproteinemias to be identified in the studied age groups. The Kharkov children were demonstrated to have high TC and T levels and relatively low HDL cholesterol, i. e. they had unfavourable characteristics as to atherogenesis. The findings suggest that the factors that influence the formation of atherogenic dyslipoproteinemias should be further studied and the preventive measures aimed at normalizing the lipid spectrum should be implemented. PMID- 1405240 TI - [Morphometric characteristics of coronary atherosclerosis in different ethnic groups of Andizhan population]. AB - A gross morphometric study of coronary atherosclerosis was performed in 554 native males aged 20-59 years and 142 migrant males of the same age from Andizhan according to the WHO Expert Programme (Bull, WHO, 1976, vol. 53, p. 485). The migrants over 40 years displayed a greater extent of atherosclerosis (except lipid streaks) than did the natives; but there were small differences between the comparable groups of young persons under 40 years. A histometric study of the coronary arteries was made in 81 apparently healthy males indicated that fine dropped (mainly intracellular) lipid deposits were more common in the natives, mixed (fine- and coarse-dropped) and coarse-dropped lipid deposits occurring with cell breakdown were seen in the migrants. The thickness of atherosclerotic lesions in the coronary arteries was greater in the migrants. Varying degrees of coronary intimal hyperplasia were found in individuals from the comparable ethnic groups. The hyperplasia was more profound in the migrants. There was a direct relationship between its degree and the development of atherosclerotic lesions. PMID- 1405241 TI - [Prognostic significance of bicycle ergometry test in patients with myocarditis]. AB - A total of 42 patients with rheumatic carditis were examined in the acute subacute period and following 3-5 years. Seventeen patients were diagnosed as having primary rheumatic carditis, 9 presented with tonsillogenic rheumatic carditis, and 16 had viral rheumatic carditis. The diagnosis of myocarditis was established on the basis of clinical, immunological, and virological findings. The study involved ECG, PhCG, PCG, and bicycle ergometer testing recordings. Groups of patients with good and poor prognosis were identified. Low threshold exercise, exercise-inadequate tachycardia, complex cardiac arrhythmias, phasic myocardial hypodynamic syndrome and volume exercise syndrome that are formed during performance are prognostically poor indicators. More profound electric and mechanic dysfunctions were observed in patients with tonsillogenic or viral myocarditis. PMID- 1405242 TI - [Acute heart failure and its treatment in cardiologic drug poisoning]. AB - The causes of sudden cardiac arrest (SCA) and its associated early death were examined in 179 patients with acute intoxications due to amitriptyline, antiarrhythmic agents and cardiac glycosides. In the first hours of intoxication, various cardiac conduction disturbances were found to occur in 39.6% of the patients, among whom 11.7% died due to SCA predominantly in complete bundle branch block. The cause of SCA was an acute (contractile) heart failure that had run as cardiogenic shock and been associated with the specific selective action of the agents in question on cardiomyocytes. Premodulation of acute heart failure with membrane protective agents (unithiol, alpha-tocopherol, hydrocortisone), pharmacological antagonists (novodrin, alupent, isoprenaline), and the cardiotonic agent dobutamine enabled acute heart failure to be effectively treated, hemosorption to be made in early periods and cardiac events to be abolished in 80% of the patients, SCA mortality rates decreased from 11.7 to 3.2%. PMID- 1405243 TI - [Functional significance of 2 pathways of energy transport in cardiomyocytes]. AB - To study the relative roles of creatine kinase (CK) and adenylate systems in cardiac energy turnover, the effect of CK inhibitor, iodoacetamide- (IAA, 0.5 mM), and 2-deoxyglucose-(DOG, 2 mM) induced) 65% depletion of adenine nucleotides at slightly decreased CK flux was determined in isolated rat heart. Both substances did not substantially affect contractile parameters of the isovolumic heart. However, an augmentation of cardiac work induced by isoproterenol addition was feeble and transient in IAA-treated hearts while the response of DOG-treated hearts was well preserved. The cardiac failure after IAA treatment was associated with irreversible fall in myocardial ATP content as evidenced by 31P-NMR technique. Furthermore, these hearts were unable to perform cardiac pump function due to insufficient cardiac filling and distensibility. The DOG-treated hearts exhibited 50% reduction in the pump function and were able to increase their work in elevated resistance. The results suggest that CK pathway is extremely important for both full cardiac relaxation and maximal contractile function. PMID- 1405244 TI - [A case of mitral valve prosthetics in subtotal left atrial thrombosis]. PMID- 1405245 TI - [Effects of prolonged-action nitrates on platelet aggregation and prostaglandin formation]. AB - Platelet aggregation and prostaglandin levels were examined in 50 patients with coronary heart disease concurrent with Functional Classes II-III angina who received nitroglycerin-retard (n = 20; Group 1), corovas (n = 20; Group 2), and placebo (n = 10; Group 3). Long-acting nitrates were found to exert a positive action on thrombocytic hemostasis as decreased platelet aggregation and reverse aggregation in 25% of the corovas-treated patients. Placebo failed to have the same action. Nitroglycerin-retard caused an increase in prostacyclin concentrations. Nitroglycerin-retard and corovas produced a clear-cut antianginal effect. They promoted the reduction in the number of anginal episodes and of nitroglycerin tablets used. No antianginal effect was absent when placebo was used. PMID- 1405246 TI - [Hemodynamic changes in bundle-branch block]. AB - The paper gives the data on hemodynamic features in patients with bundle-branch block. Based on the data available in the literature, the authors outline hemodynamic abnormalities occurring in various bundle-branch blocks, mechanisms of their development, influences of hemodynamic changes occurring in the blocks on the general condition of patients. PMID- 1405247 TI - [Effects of calcium antagonists on carbohydrate and lipid metabolism]. PMID- 1405248 TI - [Late ventricular potentials and left ventricular performance in patients with hypertrophic cardiomyopathy]. AB - Twenty patients with hypertrophic cardiomyopathy were examined. They were found to have late ventricular potentials in the disease, which were characterized by an increase in average QRS complex duration, a decrease in voltage, and a rise in the duration of last 40 msec of the QRS complex filtered. Such patients generally exhibited lower exercise tolerance in severe asymmetric left ventricular hypertrophy, which caused a significant deterioration of cardiac pump function. PMID- 1405249 TI - [Cellular mechanisms of impaired cardiac energetics in patients with dilated cardiomyopathy: decrease in mitochondrial respiration and creatine kinase expression]. AB - The mitochondrial functional characteristics were assessed in the biopsy specimens from patients with various Functional Classes dilated cardiomyopathy (DCMP). The assessment was made by using endomyocardial biopsy specimens weighing 2-4 mg which had been taken from 39 patients aged 19-64 years during coronary ventriculography and cardiac transplantation. The status of mitochondria and the efficiency of mitochondrial creatine kinase functioning were evaluated by recording the respiration of saponin-skinned muscular fibers. The maximum mitochondrial respiration rate calculated on a dry weight basis was not substantially different in all functional classes of DCMP, while the acceptor control index (Vmax/V0) and the level of creatine-activated respiration decreased with an increase in the functional class of DCMP. The findings show a good positive correlation between ejection fraction and creatine-stimulated respiration values and a linear negative correlation between this parameter and end-diastolic pressures. Thus, the respiratory parameters of mitochondria in the endomyocardial biopsy specimens may be used to assess the severity of cardias lesions. PMID- 1405250 TI - [Clinical effectiveness and effect on the sympathetic-adrenal system of a new calcium antagonist nisoldipine (Siscor) in hypertensive patients]. PMID- 1405251 TI - [Comparative study of the action of Finoptin, Korinfar and Capoten in patients with stage II hypertensive disease]. AB - The effects of Finoptin, Corinfar, and Capoten were examined in 154 patients with Stage II hypertensive disease. The calcium antagonists Finoptin and Corinfar, as well as Capoten were equal in lowering blood pressure and having a heterodirectional action on cardiodynamics: Finoptin exerted a positive inotropic effect in 46.3% and a negative one in 53.7%, corinfar in 66.7 and 33.3%, respectively, and Capoten in 37.5 and 62.5%. The baseline hemodynamic type fails to predict how the myocardium in a particular patient will respond to the antihypertensive drug. Nevertheless, Corinfar is more preferable in patients with hypertensive disease attended by hypokinetic circulation, Capoten is more preferable in those with its hyperkinetic variant. The baseline hemodynamic type makes an insignificant contribution to the activity of Finoptin. PMID- 1405252 TI - [Significance of left ventricular structural changes in arterial hypertension for the prolongation of electric cardiac systole]. AB - Echocardiography was used to examine 93 patients with Stages I and II arterial hypertension with a view to clarifying the impact of structural changes occurring in the left ventricle in the course of the disease on the duration of electric systole. Left ventricular muscle mass was found to become larger with an increase in corrected Q-T interval duration, the upper dependence correlating better with concentric hypertrophy. The duration of electric systole increased with deteriorated left ventricular function. It was empirically concluded that the left ventricular mass index of 200 g was associated with prolonged Q-T interval, which was more than the normal parameters. PMID- 1405253 TI - [Methodologic features of determining renin-like activity in human arteries]. AB - Human arterial tissue was shown to have renin-like activity. For its determination the authors propose methodological approaches. The optimum pH of renin activity in the vascular wall was found to be 5.8-6.0. The renin-like enzyme was ascertained to be present in the vascular wall as inactive and to be activated by trypsin. The renin activity was compared in the human vascular wall and human plasma. Their optimum pHs were nearly identical. The methodological features determined in this paper allowed one to differentiate the true renin like activity from the activity of acid proteases. PMID- 1405254 TI - [The baroreceptor reflex as a predictor of crises in arterial hypertension]. AB - The sensitivity of baroreceptor reflex was determined by the "neck chamber" method at a pressure of 40 mm Hg in patients with mild, moderate and malignant arterial hypertension (AH). A 24-hour blood monitoring was performed in patients with mild and moderate AH. There was a negative correlation between the lowering values in blood pressure on baroreceptor stimulation and the incidence of hypertensive crises in all the groups. There was also a negative correlation between the baroreceptor sensitivity and the daily blood pressure variations in patients with moderate AH. The findings suggest that a decrease in baroreceptor sensitivity might be a predictor of the critical course of AH. PMID- 1405255 TI - [Effect of hemosorption on microcirculation, humoral autoimmunity and lipid peroxidation in patients with stable angina pectoris]. AB - Microhemo- and lymphocirculation, capillary permeability, humoral autoimmunity and lipid peroxidation were determined in 46 patients with Functional Classes III IV stable angina concurrent with multiple atherosclerotic coronary lesions 24 hours following the second hemosorption session. The clinical efficiency of hemosorption was observed in 47.8% of patients with stenotic coronary atherosclerosis refractory to antianginal therapy. In this group of patients, hemosorption led to accelerated microcirculation, increased microcirculatory reserve potentials and decreased microvascular resistance at rest and in reactive postischemic hyperemia. In patients with abnormal humoral autoimmunity and lipid peroxidation, hemosorption resulted in their hormalization. PMID- 1405256 TI - [Cardiolipin antibodies in patients with myocardial infarction and unstable angina pectoris]. AB - The clinical value of IgG and IgM cardiolipin antibodies (CLa) was examined in 22 patients with myocardial infarction and 9 patients with unstable angina (UA). Higher IgG levels were observed in 41% of MI patients and 55% of UA patients. There was a significant correlation between the detection of IgG CLa in patients with a history of myocardial infarction and the presence of left ventricular intracavitary thrombosis. The levels of IgG CLa were increased in 78% of patients with history of MI and in 32% without MI history. In addition, those of IgG CLa was higher in 80% of IM patients with signs of intracavitary thrombosis and in 38% with cavitary thrombosis. The findings suggest that antibodies to cardiolipin (of IgG in particular) make contribution to the development of thrombotic events in patients with coronary atherosclerosis in the absence of autoimmune pathology. PMID- 1405257 TI - [Clinical and hemodynamic effect of piracetam (Nootropil) in elderly and very old patients with coronary heart disease in the outpatient rehabilitative period]. AB - The clinical and hemodynamic efficiency of piracetam (nootporil) used in the long term combined therapy of elderly and senile patients with chronic coronary heart diseases was studied outpatiently. This drug led to a significant enhancement of the antianginal effect of the basic treatment, to more regression of clinical signs of chronic circulatory insufficiency, to positive central hemodynamic changes, higher exercise tolerance, lower energy consumption index per performance unit, increased adaptive potential of the circulatory system, and maintained optimal cerebral blood flow. PMID- 1405258 TI - [Clinical course of the disease, myocardial functional status and rheological properties of blood in patients with post-infarction cardiosclerosis and angiographically documented unchanged coronary arteries]. AB - The clinical course of the disease, myocardial functional status and blood rheological properties were examined in coronary heart disease patients with postinfarction and angiographically evidenced intact coronary arteries. This group of patients was shown to be characterized by young age, acute onset of the disease and rather favourable prognosis. The abnormalities were caused by extended postinfarction asynergies, yet there was no significant progression of circulatory insufficiency even in patients with left ventricular aneurysm during a long-term follow-up (5.2 +/- 0.2 years). A correlation was found between the level of myocardial blood flow and the degree of disturbed blood rheological properties. It is suggested that impaired blood rheology along with altered coronary tone should determine the functional component of coronary resistance and represent a main mechanism of coronary insufficiency in patients with coronary heart disease and unchanged coronary arteries, as evidenced by angiography. PMID- 1405259 TI - [Phenotypic familial correlations of prostacyclin and thromboxane A2 levels in children and adolescents with or without hereditary predisposition to ischemic heart disease]. AB - The familial correlations of prostacyclin and thromboxane levels were examined in 90 children and adolescents from 70 families with hereditary coronary heart disease and in 56 of the same age from 38 families without hereditary atherosclerosis and their parents. The genetic factors were demonstrated to make a significant contribution to the phenotypic dispersion of prostanoids. The familial predisposition to the disease was ascertained to modify the pattern of familial correlations of prostacyclin and thromboxane levels as compared with no predisposition. The influence of familial and environmental factors was found to be more pronounced in the families of patients with coronary heart disease, and one of the important sequelae is thromboxane hyperproduction in the patients' wives. PMID- 1405260 TI - [Cardioprotective effects of adaptation to restraint stress and hypoxia]. AB - Isolated rat heart experiments have revealed that restraint stress adaptation results in enhanced resistance of the isolated heart to reperfusion. There is also a higher resistance to the autolysis of the organelles isolated from the hearts of stress-adapted animals. This complex of changes is designated as a phenomenon of adaptive stabilization of structures (PhASS). The phenomenon developing in restraint stress adaptation substantially limits arrhythmias, contracture, contraction amplitude depression, and creatine kinase release into the perfusate in thermal damage to the isolated rat heart. Simultaneously, PhASS is accompanied by a multiple increase in five hsp70 isoforms with pI 5.8-6.3 in cytosol and two isoforms with pI about 6.3 in the nucleoplasm. Only two hsp70 isoforms with pI about 5.8 accumulate solely in cytosol during adaptation to intermittent hypoxia. Consistently, the resistance of Ca(2+)-pump and nuclear DNA remains unchanged and the protection against reperfusion and thermal damage are several times less pronounced. PMID- 1405261 TI - [Effect of exogenous creatine phosphate on electrophysiologic myocardial parameters in overload heart failure]. AB - Experiments with rats undergoing overload testing showed that exogenous creatine phosphate was likely to fail to penetrate into myocardiocytes and to affect their energy balance directly. However, during its long-term administration in energy deficiency, creatine phosphate was able to maintain cardiac pump function via activation of processes controlling sinus nodal automatism and atrioventricular conduction. PMID- 1405262 TI - [The course of chronic circulatory insufficiency in patients with primary pulmonary hypertension]. AB - A physical and X-ray examination and echo-, electro- and phonocardiographies were performed in 29 patients with primary pulmonary hypertension. Their central hemodynamics was also conducted by introducing a Swan-Ganz flowing balloon catheter into the right cardiac cavities. With evolving chronic circulatory insufficiency, the patients showed profound hemodynamic changes both in the right (end-diastolic pressure in the right ventricle and atrium rose and ventricular stroke index dropped) and left (heart rate increased, cardiac and stroke indices decreased in the ventricle) ventricles. There were slight changes in peripheral hemodynamics. Pulmonary pressure became lower, but this fact cannot be considered to be positive as this led to significantly lower right ventricular stroke index that indicates the critical diminution in right ventricular performance, unlike cases successfully treated with peripheral vasodilators. PMID- 1405263 TI - [Experimental ultrasound contrast study of the myocardium]. AB - The ultrasound contrast medium obtained by the original methods was administered into the left ventricular cavity and myocardium of 12 open-chest dogs by using a catheter. After its administration into the cavity there was its intensive contrast. When the ultrasound contrast was administered into the aortic root, the entire myocardium contrasted, on selective administrations of the contrast into the coronary arteries, the beds supplied by appropriate arteries contrasted. The ultrasound contrast study enabled the areas with impaired perfusion as echo negative "filling defects" to be detected and mapped. The imaging of myocardial blood flow in tomographic sections and real time allows one to regard it promising for clinical use. PMID- 1405264 TI - [Effect of high-frequency pulse ultrasound on experimental myocardial infarction]. AB - The rat precardial region was exposed to single 30-minute and course radiations with pulse ultrasound at 2640 kHz before and after experimental myocardial infarction. Ligation of the left coronary artery caused an increase in 99mTc pirphotech accumulation by 243.4% as compared with the controls. Single and course ultrasounding after left coronary ligation substantially decreased rat myocardial isotope accumulation (by 130 and 179.1%, respectively) and reduced the number of complications, and prolonged animals' survival. PMID- 1405266 TI - [Origin of the aorta and pulmonary artery from the right ventricle: anatomic and echocardiographic comparisons]. AB - The origin of the aorta and pulmonary artery from the right ventricle is a complicated and little studied congenital cardiac malformation. The A. N. Bakulev Institute of Cardiovascular Surgery, USSR Academy of Medical Sciences, have developed anatomic and morphological criteria for the malformation. With the criteria, echocardiograms from 64 patients were retrospectively analysed and their anatomic and echocardiographic comparisons were made. The findings revealed the echocardiographic measures of the aorta and pulmonary artery from the right ventricle and determines the optimal echocardiographic projections for their estimate. PMID- 1405265 TI - [Exercise-induced cardiodynamic changes in invalids after leg amputation]. AB - Cardiodynamic studies by one-dimensional echocardiography were performed in 45 disabled persons with various lower limb amputations at rest and during graded bicycle ergometer exercises. The disabled included males aged 20-40 years with posttraumatic limb amputations who had no respiratory and circulatory disorders. The results of the studies were comparable with the data obtained in the control group. The handicapped were found to have significant cardiodynamic changes which were regarded as sequelae of weight and vascular bed loss. On exercise, there was loss of capacity to adequately enhance venous return and left ventricular diastolic filling, which was evidenced by concurrently decreased end-systolic and end-diastolic volumes and no increased systolic ejection. At the same time there was a regular reduction in myocardial contractility. PMID- 1405267 TI - [Functional state of the heart in ventricular tachycardia as evidenced by radionuclide ventriculography]. AB - The paper presents the results of examining the structural and functional parameters of the ventricles in 40 patients with ventricular tachycardia by radionuclide ventriculography on the first passage of a radioactivity bolus. Twenty patients had ventricular tachycardia resistant to antiarrhythmic agents. The patients with ventricular tachycardia were found to have systolic and diastolic dysfunction of the both ventricles. Lower pump function and higher volumetric parameters of the left ventricle in patients with refractory ventricular tachycardia concurrent with hyperkinesia of some right ventricular segments and abnormal velocity and time variables can be a criterion for resistance to antiarrhythmic agents in this group of patients. PMID- 1405268 TI - [Effect of thrombolytic therapy with intravenous streptokinase on the size of myocardial infarction estimated by the ECG QRS score system]. AB - The impact of short-term intravenous large dose streptokinase injection on the myocardial infarction size estimated by a QRS score system was studied in 57 patients with primary myocardial infarction admitted to hospital at least 6 hours following the onset of the disease. There was a lower myocardial infarction size despite its localization and the time of treatment initiation when thrombolysis was successful, as evidenced by non-invasive criteria. The reliability of the QRS score system used to estimate the myocardial infarction size increased when the patients with anterior or inferior myocardial infarction and those with successful and unsuccessful systemic streptokinase thrombolysis. PMID- 1405269 TI - [Structural and functional parameters of the myocardium and atrial natriuretic peptide in atrial fibrillation]. AB - The plasma level of atrial natriuretic factor and its relation to intracardiac and systemic hemodynamic parameters were examined in patients with coronary heart, rheumatic and mitral valvular diseases, neurocirculatory dystonia which were complicated by atrial fibrillation. The concentration of atrial natriuretic factor was found to vary with the left ventricular myocardial mass, left atrial contractility, antiarrhythmic therapy intensity and efficacy. PMID- 1405270 TI - [Significance of platelet membrane destruction in vasospastic angina pectoris during its exacerbation]. AB - The parameters of the structure and function of platelet membranes were examined in 30 patients with unstable vasospastic angina in relation to the outcome of the disease (myocardial infarction stabilization or development). The fractions of phospholipids (lysophosphatidylcholine, phosphatidylserine, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine), the levels of platelet membranous free and esterified cholesterol, plasma malonic dealdehyde and thromboxane B2, the activity of platelet superoxide dismutase and catalase were determined. The exacerbation of vasospastic angina was found to appear as accumulation of cholesterol (mainly of its fraction), an increase in platelet membranous levels of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin, accumulation of malonic dealdehyde. These changes were more profound in cases with subsequent myocardial infarctions. There were differences in the dynamics of the examined parameters in relation to the outcome of the disease. PMID- 1405271 TI - [Anaerobic threshold in patients with chronic circulatory insufficiency]. AB - To evaluate the severity of chronic circulatory insufficiency (CCI), 12 healthy subjects and 69 patients with cardiovascular diseases underwent exercise testing. Parameters such as anaerobic threshold (AT) and peak oxygen consumption (peak VO2) were measured by respiratory gas analysis to assess the circulatory insufficiency. AT decreased with an increase in New York Heart Association functional class and amounted to 18.9 +/- 4.3, 14.5 +/- 3.5, 11.6 +/- 2.9, and 7.5 +/- 2.0 ml/min/kg in Classes 1, 2, 3, 4, respectively. The peak VO2 decreased as hCCI progressed. The findings suggest that the parameters of external respiration and gas exchange are closely associated with CCI pathophysiology. The parameters may be used as objective and valid criteria for the severity of CCI and its dynamics in the course of treatment. PMID- 1405272 TI - [Hirudin therapy and blood coagulability]. AB - The changes in blood coagulative properties, which occur in the treatment with medical leeches, were studied in 57 patients with coronary heart, rheumatic and chronic pulmonary diseases. Hirudin therapy was established to affect blood coagulation. The leech salina penetrated into the skin wound to block hemostasis. Having entered the circulating blood, some part of the saliva normalized its impaired coagulative properties. The correction of the above abnormalities and related bleeding indicate it beneficial to use hirudin therapy in secondary coagulopathies and circulatory decompensation. PMID- 1405273 TI - [Hormonal aspects of the pathogenesis of cardiac arrhythmias in patients with hypertrophic cardiomyopathy]. AB - Radioimmunoassay was used to measure thyroid, somatotropic, parathyroid hormones and cyclic nucleotides in 40 patients with hypertrophic cardiomyopathy and 14 with hypertensive disease concurrent with asymmetrical myocardial hypertrophy. In the patients with hypertrophic cardiomyopathy, the mean blood concentration of thyroid, somatotropic, parathyroid hormones and cyclic nucleotides was generally within the normal ranges and similar to that in hypertensive patients with apparently healthy individuals. The patients with hypertrophic cardiomyopathy concurrent with supraventricular arrhythmias exhibited higher blood levels of total and free thyroxine and thyroxine/thyroxine-bound globulin ration than did patients without arrhythmias. The patients with hypertrophic cardiomyopathy concurrent with arrhythmias displayed increased blood levels of cyclic nucleotides. The findings suggest that thyroid hormones and cyclic nucleotides are likely to make contribution to the pathogenesis of arrhythmias in hypertrophic cardiomyopathy. PMID- 1405274 TI - [Effect of emotional stress on catecholamine and dopa levels in some central nervous regions and in the heart of experimental animals]. AB - The paper presents the results of examining the levels of dopamine, norepinephrine, epinephrine and precursors of their DOPA biosynthesis in the hypothalamus, hypophysis, medulla oblongata, adrenals and heart in miniature pigs exposed to acute stress. The acute emotional stress was shown to be characterized by a significant increase in the activity of the brain hypothalamic region, adrenals, peripheral portion of the sympathoadrenal system, as evidenced by higher norepinephrine release and hence lower neurotransmitter levels in the above structures. This resulted in abnormal physiological norepinephrine/epinephrine ratios in the central nervous system and heart, predisposing to myocardial metabolic and electric instability. PMID- 1405275 TI - [Hemodynamic effects of purine nucleosides in regional ischemia and reperfusion]. AB - The rat hearts were subjected to 60-min ischemia by left coronary artery ligation followed by 60-min reperfusion, involving intravenous adenosine inosine or guanosine given in a dose of 1 mg/kg.min-1 in the first 30 minutes of reperfusion. Ischemia and subsequent reperfusion caused a progressive decrease in cardiac output and coronary blood flow. Adenosine was found to enhance coronary blood flow and increase cardiac and stroke outputs. Inosine produced nearly the same, but less pronounced effect. Guanosine increased cardiac output without changing coronary blood flow. PMID- 1405276 TI - [Features of ECG topograms in relation to the direction of cardiac electric axis in the frontal plane]. PMID- 1405277 TI - [The use of fish oils to correct atherogenic dyslipoproteinemias]. PMID- 1405278 TI - [The study of diastolic cardiac function in clinical practice]. PMID- 1405279 TI - [Circadian rhythm in the clinical course of cardiovascular diseases. Clinical experience using Norvasc (amlodipine) in the treatment of patients with ischemic heart disease and arterial hypertension]. PMID- 1405280 TI - [Prevention of ischemic heart disease (1st lecture)]. PMID- 1405281 TI - [Use of magnesium sulfate in pirouette-type tachycardia (torsade de pointes) and other hyperkinetic ventricular arrhythmias]. PMID- 1405282 TI - [Assessment of myocardial function and metabolism in patients during aortocoronary bypass surgery after hypoxia-reoxygenation]. AB - The myocardial function and metabolism were assessed in 12 patients with coronary heart disease intraoperatively during aortocoronary bypass surgery. The antioxidative properties of the blood of the heart were found to become lower along with activated peroxidation after the major stage of an arrested heart operation, that correlated with depressed myocardial function. PMID- 1405283 TI - [Atherogenesis and serum levels of apolipoprotein E]. AB - Serum apolipoprotein (apo) E levels and their relationship with age were examined in different age groups of healthy individuals of both sexes in a Lithuanian population. The serum concentrations of apo E in patients after coronary bypass were measured and patients suffered from diabetes mellitus were also examined. The mean levels of apo E were found to be higher in healthy males than those in healthy females only in young age. Serum apo E levels were inversely associated with age (P < 0.05). Apo E levels were significantly higher in males over 45 years of age who suffered from coronary atherosclerosis and in males under 45 who had diabetes mellitus (types I and II) than those in healthy individuals (P < 0.05). There was an insignificant difference in apo E levels among healthy and diabetic females (P < 0.05). The findings demonstrated the association of increased apo E levels with atherogenesis. PMID- 1405284 TI - [Hypoalphacholesterolemia and coronary disease (an approach using a factor analysis)]. AB - The data obtained from a screening of 1,467 males aged 40-59 years made it possible to characterize the relation of dyslipoproteinemias, primarily hypoalphacholesterolemia, to the incidence of coronary heart disease and risk factors in males, by using factorial and multivariate analyses. The findings suggest that hypoalphacholesterolemia is closely associated with hypertriglyceridemia in its atherogenicity, thus from the clinical point of view low levels of HDL cholesterol should be used as a ground for thorough examination of lipid metabolism, with great emphasis on metabolic disturbances of triglyceride-rich lipoproteins. PMID- 1405285 TI - [Effects of lovastatin (mevacor) on platelet function in hypercholesterolemia in patients with ischemic heart disease]. AB - The impact of a 4-week course of lovastatin (mevacor) therapy on platelet function was examined in 26 patients with coronary heart disease concurrent with hypercholesterolemia (the baseline plasma cholesterol level was 250 mg% or more). The agent was given in a daily dose of 20-40 mg. The agent in this dose was found to have no action on the thromboxane-prostacyclin balance in plasma, on the degree of ADP-induced aggregation and lipid peroxidation in platelets, phospholipid composition and levels of ester-bound cholesterol in platelet membranes. Free cholesterol tended to increase at the end of the 4th week of treatment. Despite the effective reduction of plasma levels of total and LDL cholesterols whose action on platelets is well known, there was no estimated decrease in the activity of platelets during lovastatin therapy. PMID- 1405287 TI - [Effects of laser therapy in patients with functional class II-IV effort angina (using instrumental techniques of the study)]. AB - Infrared laser therapy using an arsenide-gallium laser was used in 54 patients aged 30-75 years who suffered from coronary heart disease. A positive clinical effect was achieved in 47 (87%) of 54 patients, as evidenced by the reduced number of nitroglycerin tablets used and improved bicycle ergometric, echo- and electrocardiographic parameters in the patients. PMID- 1405286 TI - [Effects of lovastatin therapy on the level of low density lipoproteins and atherogenic potential of serum in patients with ischemic heart disease and hypercholesterolemia]. AB - The serum atherogenic potential in patients with coronary heart disease (CHD) concurrent with hypercholesterolemia (LDL cholesterol more than 200 mg/dl), which is able to cause accumulation of intracellular cholesterol in cultured cells has been recently shown to be directly related to the level of total cholesterol and LDL cholesterol. The study was undertaken to examine how a lovastatin-induced decrease in LDL levels affects serum atherogenicity in patients with CHD and hypercholesterolemia. It was shown that the therapy of 22 patients with CHD and hypercholesterolemia led to a reduction in total and LDL cholesterol levels on an average by 24% and 32%, respectively. There were 3- and 1.5-2-fold decreases in circulatory immune complexes and the atherogenic potential, respectively. The findings suggest that the significant reduction in serum LDL cholesterol levels in patients with CHD concurrent with hypercholesterolemia who take hypolipidemic therapy is followed by a decrease in the atherogenic potential. PMID- 1405288 TI - [Relationship of physical work capacity, blood pressure and other hypertension risk factors with the rate of erythrocyte Na/Li countertransport]. AB - The relationship of physical working capacity (PWC), blood pressure and other arterial hypertension risk factors to the rate of red blood cell Na+/Li+ countertransport was examined in a representative sample comprising 60 individuals (22 males and 38 females) whose age was 35-54 years. Regression analyses demonstrated that there was no significant relationship between PWC and the rate of red blood cell Na+/Li+ countertransport, but a significant correlation was found between the rate of Na+/Li+ countertransport and "double product" (DP) as an indirect indicator of PWC and heart rate. Thus, there is a heart rate- and DP-mediated correlation between the rate of red blood cell Na+/Li+ countertransport and the level of PWC. The magnitude of a decrease in the rate of red blood cell Na+/Li+ countertransport depends inversely on the dynamics of heart rate in males and females and directly on the dynamics of DP in females. Hence, there is a direct relationship between the magnitude of a reduction in the rate of red blood cell Na+/Li+ countertransport and that of PWC increment during exercise. PMID- 1405289 TI - [Transesophageal electric stimulation of the left atrium in the diagnosis of ischemic heart disease in patients with arterial hypertension]. PMID- 1405290 TI - [Comparative analysis of antiarrhythmic action and electrophysiological effects of a new benzodiazepine derivative gidazepam and ethacizin in arrhythmias of various genesis]. AB - The antiarrhythmic and electrophysiological effects of the new benzodiazepine tranquilizer gidazepam versus ethacizin were examined in patients with cardiac arrhythmias. The antiarrhythmic effect of the agent was found during 24-day monitoring and simulated psychoemotional stress in 81% of patients with neurocirculatory dystonia and in 61% of patients with coronary heart disease. The antiarrhythmic effects developed with gidazepam-induced changes in electrophysiological properties of the cardiac conduction system. The preventive antiarrhythmic effect of gidazepam was demonstrated to be higher than that of ethacizin during stress in patients with arrhythmias of extra-ischemic genesis. PMID- 1405291 TI - [Clinical effectiveness of cordarone in combination with other anti-arrhythmia agents in refractory atrial fibrillation and adverse effects of the drugs]. AB - The study was undertaken to examine 105 patients with various circulatory diseases complicated by atrial fibrillation. Patients with refractory atrial fibrillation who had taken combined antiarrhythmic therapy were found to be more responsive to the combinations of cordarone + kinilentin (quinidine disulphate) and cordarone + ethacizin. The combinations of cordarone+digoxin and cordarone + finoptin were demonstrated to be less beneficial. PMID- 1405292 TI - [Arrhythmia in athletes during length diving]. AB - On diving at a distance of 50 m by arresting their breathing, some male athletes were shown to develop cardiac arrhythmias which occurred at min 2 of a restorative period and entirely disappeared at the end of the second-fifth min. It is essential to make further studies of the impact of diving on the cardiac rhythm in athletes in order to elucidate how these disturbances should be regarded: abnormal or physiological. PMID- 1405293 TI - [Results of closed mitral commissurotomy after 20-25 years]. AB - The 20-25 year results of 486 closed mitral commissurotomies were analysed. The actuarial analysis demonstrated that 25-year survival was 59%, stable good results were 38%, repeated mitral interventions were performed in 31% of the patients. The patients' survival and functional results of commissurotomies depend on early surgery which should be done in patients with severe and acute mitral stenosis prior to the development of drastic valvular changes, calcinosis, regurgitation, atrial fibrillation, cardiomegaly, atrial thrombosis and other complications. Timely mitral commissurotomy is a rather effective palliative intervention in uncomplicated mitral stenosis. PMID- 1405294 TI - [ECG dynamics at rest and during exertion after mitral commissurotomy]. AB - Four degrees of left atrial electrical activity were identified by ECG made before and after closed mitral commissurotomy in 70 patients with mitral stenosis and sinus rhythm. The critical electrical activity of the left atrium and hypertrophy of the right ventricle along with the typical auscultation pattern of mitral stenosis were found to cardiographically correspond to critical stenosis of the left atrioventricular ostium in most cases. The area of the mitral orifice, which was attributable to that of the body, was 0.6 to 0.8 cm2/m2. The patients with critical left atrial electrical activity were considered to be at risk for atrial fibrillation in the immediate postoperative period. PMID- 1405295 TI - [Assessment of the quality of life of patients with rheumatic mitral defects: methodological approaches]. PMID- 1405297 TI - [Doppler echocardiography in the assessment of arteriovenous blood ejection in patients with ventricular septal defects]. AB - To assess Doppler echocardiography used to determine blood ejection through ventricular septal defect, this procedure and cardiac catheterization were performed in 32 patients. Comparison of the findings showed a high correlation (r = 0.81; p < 0.05). To determine whether echocardiographic accesses are correctly chosen, volumetric greater circulation was measured from the suprasternal access in the ascending aorta and aortic arch, but volumetric lesser circulation was measured from the parasternal access in the pulmonary trunk and from the apical access of the projection of 4 chambers through the mitral orifice. The comparison of the findings showed a high correlation in this group. Twenty one patients were examined after plastic surgery of ventricular septal defect, who had been clinically suspected to have a residual shunting. An analysis of the findings made it possible to develop Doppler echocardiographic criteria for differential diagnosis of graft vibration due to arteriovenous blood ejection. PMID- 1405296 TI - [State of coronary circulation and results of 24-hour ECG monitoring in patients with refractory angina pectoris]. AB - The paper compares the data of selective coronary angiography and 24-hour monitoring in 39 patients with refractory angina pectoris. Transient ST-segment changes were revealed in 79% of the patients, ST-segment depression occurring in 54%, ST-segment elevation in 46%, T-wave inversion in 38%. A combination of ST-T interval changes and occurrence of ventricular premature contraction was found in a third of the examinees. There was no statistically significant correlation between the extent of major coronary lesion and the mean length of ST-segment displacements. PMID- 1405298 TI - [Effects of adaptation to periodic hypoxia on Ca2+ pump of the cardiac sarcoplasmic reticulum and its resistance to endogenous damaging factors]. AB - The adaptation of rats to periodic "altitude" hypoxia in the altitude chamber (6 hour daily at an altitude of 5000 m during a month) led to increased activity of the Ca2+ pump in the myocardial sarcoplasmic reticulum, which was associated with lower Kd values and higher calcium transport Vmax. When a cardiac homogenate was kept at 4 degrees C, autolysis resulted in a decrease in Ca2+ pump activity (which was more rapid in adapted animals than in the controls) and an equal increase in the levels of free calcium in the homogenates in the two series of experiments. The approximate data were obtained when a homogenate was incubated at 37 degrees C, but when it was incubated at 4 degrees C, the rate of Ca(2+) pump inactivation decreased 20-fold. Incubation in the presence of free radical oxidative inductors (Fe2+ ascorbate) led to high resistance of myocardial Ca(2+) pump in the adapted rats. The paper discusses the causes of myocardial Ca(2+) pump activation in periodic hypoxic adaptation and the mechanisms for its increased resistance to active oxygen, as well as their role in the cardioprotective effect of the adaptation. PMID- 1405299 TI - [Effects of bonnecor on transmembrane potentials of cardiomyocytes of the ventricular contractile myocardium of the intact heart and ventricular fibrillation]. AB - The microelectrode technique has shown that bonnecor given in a dose of as many as 2 mg/kg increases the action potential amplitude, but when its dose is increased up to 3 mg/kg, the agent decreases the action potential amplitude of ventricular cardiomyocytes in the guinea-pig, the resting potential remaining steady. Administration of bonnecor prevents ventricular fibrillation after aconitine application and provokes ventricular fibrillation and flutter when the focus of ectopic automatism is formed. PMID- 1405300 TI - [Specific features of the regulation of coronary circulation during reperfusion after coronary insufficiency of different degrees]. AB - Coronary insufficiency of various degrees was reproduced in experiments with anesthetized dogs by using coronary artery catheterization by progressively limiting the regional blood flow by 30, 50, 70, and 90%, the dog chest being closed. The specific features of regulatory reactions of cardiac vessels were also studied under subsequent reperfusion. It was shown that regulation of coronary circulation became changed in most cases after markedly limited coronary blood flow, as manifested by impaired reperfusion hyperemia and its rapid cessation that prevented the "payment" of blood flow debt and a secondary increase of cardiac vascular resistance above the preocclusive level. There was a significant relationship between the detected disorders and the degree of prior limited coronary perfusion. PMID- 1405302 TI - [Echocardiographic assessment of cardiac pump function using afterloading characteristics]. AB - Seventy five patients and twenty healthy individuals were investigated by using cardiac ultrasound technique, followed by mathematical simulation of changes in left ventricular pressure during contraction. The findings show that the afterload characteristics based on a wealth of evidence for cardiac and left ventricular performance, unlike the conventional central hemodynamic parameters and cardiac phasic indices, enable the occult circulatory disorders to be revealed and the cardiac compliance with the arterial system to be assessed. PMID- 1405301 TI - [Atherogenic properties of phenothiazine drugs manifesting in cultured cells of the human aortic intima]. AB - The effects of phenothiazine drugs on the levels of cholesterol in smooth cells of the human aortic intima. Two antiarrhythmics (ethacizin and ethmozine) and two neuroleptics (trifluoperazine and chlorpromazine) were evaluated. The three agents ethacizin, trifluoperazine, and chlorpromazine given in concentrations of 10(-7) to 10(-5) M were ascertained to cause intracellular cholesterol accumulation, whereas ethmozine produced no effects on the intracellular levels of cholesterol. Ethacizin failed to cause cholesterol accumulation when the cells were incubated with ethacizin in the culture medium supplemented with lipid deficient serum. Ethacizin in a concentration o 10(-5) M was shown to inhibit the synthesis of cholesterol esters and had no action on the intracellular synthesis of steroids. PMID- 1405303 TI - [Doppler echocardiographic assessment of left atrial and left ventricular function during right bundle branch block]. AB - Electrocardiographic, echocardiographic and Doppler echocardiographic studies were performed in 44 patients with coronary heart disease and complete right bundle branch block. The patients were found to have an impaired phase pattern of left ventricular systole and diastole as more prolonged length of its isometric relaxation and contraction, lower economic feasibility and efficiency of its contraction, moderate dilation and hypertrophy. Hemodynamic abnormalities in the left heart in these patients are closely correlate with the changes in the phase pattern of right ventricular systole and they turn out to be so greater as the degree of its hypertrophy is. In complete right bundle branch block, left ventricular pump dysfunction leads to decreased cardiac output and cardiac index, increased total peripheral vascular resistance, thus predisposing to impaired greater circulation. PMID- 1405304 TI - [Cardiac diastolic function in children and adolescents during prompt and long term adaptation to physical exercise]. AB - To study the natural changes in cardiac diastolic function in ontogenesis at various stages of exercise adaptation, 65 males aged 10-17 years who go in for various kinds of sports developing primarily physical fitness have been examined. Long-term adaptation to cyclic muscular activity has been shown to result in a reduction in cardiovascular lability, an optimization of inclusion of myocardial functional reserves, and an increase in efficiency of using cardiac cycle time in response to myocardial restorative processes. High stages of exercise adaptation formed an additional mechanism responsible for diastolic filling at the expense of an atrial systole (an atrial mechanism of diastolic regulation). PMID- 1405305 TI - [Intraoperative myocardiography, a new method of regional myocardial function evaluation during aortocoronary bypass surgery]. AB - Excursions of the myocardium in its revascularization area were recorded in 70 patients with coronary heart disease. Myocardial dyskinesia correlated with low bypass blood flows, myocardial ischemia and infarction in the area of revascularization at any blood flow values. The evaluation of the diagnostic efficacy of myocardiographic symptoms suggested that myocardiography had some advantages. It was concluded that it was essential to include intraoperative myocardiography into the set of methods for examining patients with coronary heart disease during myocardial revascularizations. PMID- 1405306 TI - [Role of coronary collateral circulation in the compensation of disorders of myocardial perfusion and left ventricular function in patients with newly appearing angina pectoris]. AB - The myocardial perfusion and left ventricular function were evaluated by bicycle ergometry and myocardial scintigraphy in 23 patients with primary angina taking into account the status of coronary collateral circulation in response to stenotic and occlusive atherosclerosis. In addition to severe occlusive disease of the coronary bed, most patients had significant disturbances of myocardial perfusion and left ventricular function, which were detected during exercise tests. In patients with compensatory collateral circulation in the coronary bed, such disturbances were less marked than in those without anastomoses. However collateral coronary circulation cannot be regarded to be of real value as it compensates impaired perfusion incompletely, but in some cases it can result in impaired myocardial vascularization apparently due to the steal syndrome. PMID- 1405307 TI - [Plasmapheresis in the treatment of patients with cardiovascular disorders]. PMID- 1405308 TI - [ECG atrial complex changes in patients with diabetes mellitus]. PMID- 1405309 TI - [Discussion of Professor V. S. Volkov's article, The role of spasm in the pathogenesis of angina pectoris, published in Kardiologiia, No. 12, 1990]. PMID- 1405310 TI - [Drug treatment of arrhythmia. Clinical experience with anti-arrhythmia preparation ritmonorm (propafenone)]. PMID- 1405311 TI - The cellular action of aldosterone in target epithelia. PMID- 1405312 TI - Effect of K depletion on renal K and Rb excretion: evidence for activation of K reabsorption. AB - Prolonged potassium depletion activates tubular transport mechanisms mediating potassium absorption. To study ion specificity and factors that modulate the activity of potassium transport pathways, fractional potassium excretion (FEK) was compared with that of rubidium (FERb) in control and potassium-depleted rats subjected to various experimental maneuvers. In control rats FEK considerably surpassed FERb (FEK/FERb 1.54 +/- 0.08; mean +/- SEM), whereas in potassium depleted rats FEK was significantly lower than FERb (FEK/FERb 0.72 +/- 0.05). Preferential retention of potassium compared to rubidium in potassium-depleted rats was accentuated (FEK/FERb 0.33 +/- 0.01) when residual potassium secretion was inhibited by amiloride and K-H exchange stimulated by increased distal buffer delivery (metabolic alkalosis). When distal fluid and buffer delivery were increased in control animals by acetazolamide, FEK and FERb rose in parallel. In potassium-depleted rats only FERb but not FEK was enhanced by acetazolamide. These data demonstrate that both potassium secretory and potassium absorptive transport pathways prefer potassium to its congener rubidium. Prolonged potassium depletion activates a potassium absorptive mechanism which is stimulated by increased distal buffer delivery and which transports potassium more effectively than rubidium. PMID- 1405313 TI - Cultured mesangial cells from autoimmune MRL-lpr mice have decreased secreted and surface M-CSF. AB - M-CSF has been implicated in the pathogenesis of lupus nephritis in MRL-lpr mice. We recently reported persistently high levels of serum M-CSF in MRL-lpr mice as early as one week of age, not present in normal mice including C3H mice. In addition, M-CSF transcripts in MRL-lpr renal cortex increased with an increase in the severity of nephritis. Because glomerular mesangial cells (MC) secrete M-CSF, we investigated whether cultured MRL-lpr MC secrete more M-CSF than C3H MC. Paradoxically, unstimulated MRL-lpr MC secreted substantially less M-CSF than C3H MC [26 +/- 11 vs. 109 +/- 7 colony forming units (CFU)]. We then explored whether MC could express membrane bound M-CSF. We detected a 31 kDa form of membrane M CSF on both MRL-lpr and C3H MC. Fewer MRL-lpr MC than C3H MC (24 +/- 5% vs. 78 +/ 5%) expressed membrane M-CSF. Furthermore, the increase in the mean channel log fluorescence intensity on MRL-lpr MC was considerably less than in C3H MC, indicating a lower density of M-CSF on MRL-lpr MC. Because our prior studies established that MRL-lpr kidneys have enhanced expression of TNF alpha, we stimulated cultured MC with TNF alpha. TNF alpha increased M-CSF secretion by stimulated MRL-lpr by twofold over unstimulated MRL-lpr MC, but did not increase M-CSF in C3H MC. In addition, M-CSF secretion was modestly greater in stimulated MRL-lpr MC compared to stimulated C3H MC. In conclusion, this is the first report of membrane M-CSF detectable on cultured MC. These studies note that despite higher circulating M-CSF and renal M-CSF transcripts in MRL-lpr mice, cultured MRL-lpr MC have lower basal secreted and membrane bound M-CSF than cultured C3H MC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405314 TI - Uninephrectomy enhances urolithiasis in ethylene glycol treated rats. AB - Uninephrectomy (uNX) usually induces compensatory hyperfunction of the remaining kidney in an attempt to preserve the homeostasis of body fluid composition. The present study used uninephrectomized Sprague-Dawley rats on a lithogenic diet (0.5% ethylene glycol, EG) to evaluate the influence on urinary stone formation and calcium oxalate crystal deposition of compensatory excretion of lithogenic substances in the remnant kidney. The results showed that there were no urinary stones or calcium oxalate crystal deposits in the intact or uNX rats fed a normal diet. In the EG feeding groups, the incidence of massive (grade 3) crystal deposits was significantly higher in the uNX rats (87.5%) than that in the intact rats (37.5%; P less than 0.05). The incidence of urinary stone formation was also higher in the uNX rats as compared to that of the intact rats, although the difference did not achieve statistical significance. The serum magnesium, phosphorus and creatinine increased significantly, whereas creatinine clearance (CCr), 24-hour urinary excretions of citrate, sodium, potassium and chloride decreased significantly in the uNX rats fed EG. These data indicate that uninephrectomy increases the vulnerability of the contralateral remnant kidney to urolithiasis and crystal deposition when the lithogenic risk factors are present. Furthermore, once the remnant kidney forms urolithiasis or massive calcium oxalate crystal deposits, the renal function is severely compromised. PMID- 1405315 TI - NaCl transport by Madin Darby canine kidney cyst epithelial cells. AB - The mechanism of NaCl transport across the epithelium of intact MDCK cysts grown in a collagen gel matrix was investigated. Double-barreled microelectrodes were used to measure basolateral membrane PD (Vbl), transepithelial PD (Vt), and intracellular (Cli) and intralumenal (Clcy) Cl- activities in cysts under different conditions. In a control Ringer's solution (RS), Cli (60 +/- 1 mM) and Clcy (107 +/- 2 mM) exceeded the values corresponding to electrochemical equilibrium across the basolateral membrane and epithelium, respectively. Cli was reduced by superfusing the cysts with a low Cl- RS (Cli, 20 +/- 3 mM), a low Na+ RS (Cli, 40 +/- 4 mM), or by adding amiloride to the control RS (Cli, 46 +/- 1 mM). Cli was unaffected by removal of either K+ or HCO3- from the RS or by adding furosemide or SITS to the control RS. Vbl in the control RS was -50 +/- 2 mV and was affected only by removal from the RS of K+ (Vbl, -31 +/- 3 mV) or HCO3- (Vbl, -29 +/- 4 mV) or by the addition of SITS to the control RS (Vbl, -59 +/- 5 mV). Vt in control RS was -2 +/- 0.2 mV (lumen negative), and was increased by reducing bath Na+ (Vt, -37 +/- 2 mV) but not by reducing bath Cl-. These data indicate that Cl- is secreted in a basolateral to apical direction by the cyst epithelium. Basolateral Cl- transport probably occurs mainly by an electroneutral Cl-/HCO3- exchanger. Transepithelial Na+ transport seems to occur via a paracellular route which appears to be cation selective. These experiments also support the existence, in the basolateral membrane, of a Na+/K+ ATPase, a Na+/H+ exchanger, and possibly a Na+/HCO3-/CO3(2-) transporter. PMID- 1405316 TI - Hemodialysis related induction of interleukin-6 production by peripheral blood mononuclear cells. AB - Interleukin-6 (IL-6) has a complex spectrum of biological activities, for example, growth and differentiation of B cells and synthesis of acute-phase proteins by the liver. To evaluate the role of this cytokine in the inflammatory response induced by blood interaction with hemodialysis membranes, we have investigated the IL-6 synthesis and release in supernatant of 24-hour cultured peripheral blood mononuclear cells (PBMC) isolated from: (a) 10 hemodialyzed patients, (b) seven patients with advanced chronic renal failure (GFR less than or equal to 10 ml/min), and (c) eight healthy control subjects. In the same groups of subjects we evaluated the relationship between IL-6 synthesis and release and beta-2-microglobulin (beta 2m) production. Before and after dialytic treatment hemodialysis patient blood samples were drawn using the following criteria: (1) after two months of dialysis with cuprophan membranes, (2) after one and two months of dialysis with polymethylmethacrylate (PMMA) membranes, and finally, (3) after one further month of dialysis with cuprophan membranes. IL-6 was determined after 72 hours of incubation of PBMC supernatant serial dilutions with IL-6-dependent hybridoma cell line, 7TD1. Compared to IL-6 synthesis in control subjects (6.0 +/- 5.6 U/3 x 10(6) PBMC/24 hr), hemodialyzed patients, when treated with cuprophan membranes, showed significantly higher value of IL-6 production both before (23 +/- 13 U/3 x 10(6) PBMC/24 hr) and after (26.2 +/- 11.3 U/3 x 10(6) PBMC/24 hr) the dialytic session.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405317 TI - Extrarenal cytokines modulate the glomerular response to IgA immune complexes. AB - Clinical episodes of IgA nephropathy coincide recurrently with microbial infections. Cytokines produced during such infections may play a role in the pathogenesis of IgA-associated glomerulonephritis. To test this hypothesis, we examined the influence of passively administered proinflammatory cytokines (IL-1, IFN-gamma and IL-6) on the development of glomerulonephritis in an experimental model of IgA nephropathy. Glomerular IgA immune deposits were induced in mice by administration of IgA anti-phosphorylcholine (PC) with either a PC-containing carbohydrate antigen of Pneumococcal C polysaccharide (PnC) or a protein antigen of PC-conjugated bovine serum albumin (PC-BSA). The effect of IL-1 on the IgA-PC BSA induced glomerular changes resulted in an increase of mesangial hypercellularity that was associated with mild proteinuria and hematuria. Mice treated with IL-1 and IgA-PnC developed diffuse proliferative glomerulonephritis with proteinuria and hematuria. In contrast, IL-6 treatment with IgA-PC-BSA of IgA-PnC failed to exert any significant renal effect. The combination of IL-6 and IL-1, however, intensified the mesangial hypercellularity of the IgA-PC-BSA, and induced severe proliferative glomerulonephritis with inflammatory monocytes and neutrophils infiltrates in the IgA-PnC treated mice. These glomerular changes were also accompanied by increased proteinuria and hematuria. Similarly, the combination of IFN with IL-1 produced histologic changes and compromised renal function more than IFN or IL-1 exerted independently. These results suggest that extrarenal cytokines influence the renal response to IgA immune deposits. We also conclude that a synergy of multiple cytokines and nephritogenic antigens immobilized in glomerular IgA immune deposits may lead to rapid progression of IgA-associated glomerulonephritis. PMID- 1405318 TI - Renal effect of anti-hypertensive drugs depends on sodium diet in the excision remnant kidney model. AB - Angiotensin converting enzyme inhibitors (ACEI) are believed to protect remnant kidney, but all previous studies used the ligation model which causes severe hypertension, and very few have compared drugs in rats having similar control of blood pressure (BP). We compared rats with uremia obtained by 70% excision of total renal mass, a model which causes mild, late hypertension. Study I compared the effects of enalapril (E), cicletanine (C) and placebo (P) in uremic (U) rats fed a 0.50% (normal-high) Na diet. Study II compared the effects of E, C, P, and guanfacine (G) in U rats fed a diet restricted to 0.25% Na (normal-low). In study I, UP rats developed progressive hypertension (140, 146, 160 and 166 mm Hg at 3, 6, 9 and 12 weeks), proteinuria (240 mg/day at 9 and 12 weeks) which were not affected by E or C. The occurrence of end-stage renal disease (ESRD) led to the sacrifice of all rats after three months. All three groups had similar severe renal lesions (over 25% sclerosed glomeruli in 5 of 10 UP, 9 of 14 UE, 7 of 14 UC rats, with huge cystic tubular dilatations). In study II, rats could be sacrificed later (6 months) and had evidence of less severe renal disease. All the drugs tested prevented hypertension throughout the study (P less than 0.001), with lowest values in UE rats. E and G, but not C, reduced proteinuria. Renal damage was reduced with E and G, but not with C, despite similar BP in C and G rats. Thus, in contrast with what was obtained in the ligation model, ACEI affected neither the BP nor the renal lesions of rats made uremic by renal excision and fed a 0.50% Na diet. Moderate Na restriction improved the consequences of nephron loss and restored the anti-hypertensive effect of drugs. However, these drugs had a different effect on renal preservation: it was dramatic with E, good with G, and undetectable with C. PMID- 1405320 TI - Binding of serum immunoglobulins to collagens in IgA nephropathy and HIV infection. AB - The mechanism of the binding of IgA to the mesangium in IgA nephropathy (IgAN) is unknown. Interactions between IgA and components of the mesangial matrix may contribute. We measured by enzyme-linked immunosorbent assay the binding of serum IgA, IgG, and IgM from patients with IgAN, human immunodeficiency virus type I (HIV) infection, and healthy controls to purified native collagen types I to VI, and to an extract of normal kidney tissue. HIV infection is an appropriate disease control because of the lack of mesangial IgA deposits, despite high serum levels of IgA and IgA1-containing immune complexes. Increased levels of IgA binding to collagen types I and V and the kidney extract were found only in IgAN. Both IgAN and HIV-infected patients had increased IgA-binding to collagen types II, III, and VI. Preabsorption of the sera with gelatin substantially reduced the IgA-binding to collagen types I to IV, but not to types V and VI. This finding suggests that the binding to collagen type V is not fibronectin-mediated, but may reflect autoantibody formation. Thus, fibronectin-mediated IgA-collagen interactions are not specific for IgAN, and their pathogenetic role is questionable. The role of IgA anti-collagen type V antibodies requires further study. PMID- 1405321 TI - IL-1 alpha stimulated TNF alpha production by cultured human proximal tubular epithelial cells. AB - Tumor necrosis factor alpha (TNF alpha) production by proximal tubuli was studied by immunoperoxidase staining of 20 renal biopsies from transplant patients. A positive staining for TNF alpha on proximal tubuli was seen in nine out of 15 patients with interstitial infiltrate, five without clinical significant rejection and four with moderate to severe interstitial rejection. TNF alpha was only expressed on tubuli within areas of interstitial infiltrate. Expression of TNF alpha in the mononuclear cell infiltrate was seen only in three patients with interstitial rejection. Absence of TNF alpha could be seen in biopsies with no renal abnormalities. To obtain more information on the regulation of TNF alpha production, proximal tubular epithelial cells (PTEC) cultures were established and assessed for production of TNF alpha. Heterogenicity in production of TNF alpha was found in 14 tested PTEC lines cultured under serum free conditions. The presence of IL-1 alpha in the cultures induced a time- and dose-dependent enhancement of TNF alpha production by PTEC. Enhanced production of TNF alpha was not seen after stimulation with other cytokines such as IL-2 or IFN gamma. Inhibition studies with cycloheximide indicated de novo synthesis of TNF alpha. Western blot analysis of supernatants of unstimulated and IL-1 alpha stimulated PTEC indicated a 17 kd product, a size similar to that of recombinant TNF alpha. Northern blot analysis revealed the presence of a 2.0 kb hybridization signal in total RNA of PTEC cultures and up regulation upon treatment of PTEC with 1 ng/ml of IL-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405319 TI - Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease. AB - Evidence suggests an important role for the renin-angiotensin system in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). Therefore, we studied the presence of immunoreactive renin in renal biopsies and measured the concentrations of renin in cyst fluids. Normal kidneys and kidneys with renal artery stenosis were used for comparison. In ADPKD, immunoreactive renin was present in juxtaglomerular apparatus, associated arterioles, and in some cells within the connective tissue surrounding the cysts. Vascular immunoreactive renin was less prominent than in renal artery stenosis. Increased amounts of tubular immunoreactive renin were noted in polycystic kidneys, as compared to normal kidneys and kidneys with renal artery stenosis. Cyst fluids contained renin detected by Western analysis and enzymatic activity; concentrations were greater in gradient cysts than in nongradient cysts. Seventy-four percent of the renin in gradient cysts was active as compared to 23% in nongradient cysts and 15% in plasma. To determine whether cyst epithelial cells are capable of synthesizing renin, these cells were isolated in tissue culture. Enzymatic assay of extracts from these cells revealed the presence of renin-like enzymatic activity (1.3 +/- 0.8 ng AI/mg protein/hr). The synthesis of renin by tubulocystic epithelium was confirmed by [35S]-methionine radiolabeling of cyst-derived cells, followed by immunoprecipitation and SDS-PAGE and by detection of renin mRNA by the polymerase chain reaction. These results indicate that the tubulocystic epithelium has the potential to synthesize renin. Elevated levels of active renin in renal cysts may be linked to the pathogenesis of hypertension in ADPKD. The occurrence of renin in the lining epithelium of cyst walls raises the possibility that abnormal expression of the renin-angiotensin system may, by a paracrine or autocrine mechanism, regulate epithelial hyperplasia in growing renal cysts. PMID- 1405322 TI - Developmental patterns of PDGF B-chain, PDGF-receptor, and alpha-actin expression in human glomerulogenesis. AB - Expression of PDGF B-chain and the PDGF receptor beta-subunit (PDGFR beta) is detected immunocytochemically during the development of glomeruli in human kidneys of 54 to 105 days gestational age. During the early stages (vesicular, comma-shape and S-shape) of glomerulogenesis, PDGF B-chain is localized to differentiating epithelium of the glomerular vesicle, while PDGFR beta is expressed in the undifferentiated metanephric blastema, vascular structures, and interstitial cells. During this stage PDGF may be acting as a paracrine growth factor and as a chemoattractant acting to recruit mesangial progenitor cells into the developing glomerulus. As the glomerular tuft forms, both PDGF B-chain and PDGFR beta can be detected in an arboreal pattern radiating from the hilus of the glomerular tuft. Immunocytochemical studies using markers specific to endothelium (Ulex europaeus I lectin, Factor VIII related antigen), and smooth muscle (alpha smooth muscle actin), indicate that the PDGF B-chain and PDGFR beta are both expressed primarily by mesangial cells. During this stage, PDGF may be acting primarily to provide an autocrine factor to mediate further mesangial cell proliferation. Glomerular expression of alpha-smooth muscle actin is limited to later stages of glomerulogenesis; at these stages the pattern of expression is similar to that of PDGF-B chain and PDGFR beta. The upregulation of mesangial PDGF, PDGFR beta, and alpha-smooth muscle actin expression that has been identified in some disease states in both humans and experimental animals appears to represent a recapitulation of this normal developmental process. PMID- 1405323 TI - A comparison of the responses to recombinant human erythropoietin in normal and uremic subjects. AB - The erythropoietic response to graded doses of recombinant human erythropoietin (epoetin alfa) was assessed in 24 hemodialysis patients by quantitative ferrokinetic studies, and measurement of the reticulocyte count and plasma levels of transferrin receptor protein. These responses were compared to those of 22 normal subjects. Epoetin alfa was given intravenously at 15, 50 or 150 U/kg every other day for four injections. Three patients with chronic renal failure were restudied after renal function was restored following renal transplantation. The results of these three different measurements of erythroid function showed that the acute response to recombinant human erythropoietin was similar in normal subjects and patients with renal failure. We conclude that chronic uremia does not alter the responsiveness to erythropoietin in vivo. PMID- 1405324 TI - Angiotensin II does not increase renal prostaglandin E2 in response to pressure reduction. AB - Whether angiotensin II (Ang II) stimulates renal secretion of prostaglandin E2 (PGE2) synthesized in response to pressure reduction was examined. PGE2 and Ang II in aortic and renal venous plasma were measured before and during renal arterial constriction in anesthetized dogs, with or without an intrarenal arterial infusion of an Ang II antagonist, losartan potassium (1 mg/min), or saralasin (3 micrograms/min). In other anesthetized dogs, two doses of Ang II (30 and then 300 ng/min) were infused into the renal artery, and plasma Ang II levels and renal PGE2 secretion were measured. When renal perfusion pressure was reduced to 75 and 45 mm Hg by constriction, the renal secretion of PGE2 increased seven- and fourfold, respectively. Ang II levels in the renal venous plasma increased from 6.6 +/- 1.8 to 21.7 +/- 7.4 and then 48.1 +/- 15.3 pg/ml (both P less than 0.05) as the pressure decreased. Neither losartan nor saralasin suppressed the response of renal PGE2 secretion to the pressure reduction. The intrarenal infusion of Ang II (30 ng/min) elevated the Ang II level in the renal venous plasma from 9.8 +/- 4.6 to 33.7 +/- 4.2 pg/ml (P less than 0.01), but did not increase PGE2 secretion. The higher dose (300 ng/min) of Ang II increased it, but the Ang II level in the renal venous plasma was 166 +/- 63 pg/ml. These results suggest that the greater part of the increased renal synthesis of PGE2 in response to pressure reduction is not mediated by Ang II. PMID- 1405325 TI - Plasma level of lipoprotein Lp(a) is high in predialysis or hemodialysis, but not in CAPD. AB - Plasma Lp(a) lipoprotein level was determined in chronic renal failure (CRF) patients, 24 before initiation of dialysis, 18 undergoing hemodialysis, and 24 on continuous ambulatory peritoneal dialysis (CAPD). Eighteen healthy subjects were studied as controls. Median of Lp(a) level in both predialysis and dialysis patients was significantly increased: 23.5 mg/dl (range: 0 to 109) and 24.0 mg/dl (range: 1.4 to 90), respectively, as compared to healthy controls: 4.7 mg/dl (range: 1.8 to 27; P less than 0.001). By contrast, the median Lp(a) level in CAPD patients, 2.4 mg/dl (range: 0 to 39.5), was similar to the control group. Whether the CAPD procedure reduces the Lp(a) level in CRF patients has to be established in a prospective study. PMID- 1405326 TI - A longitudinal, five year survey of urea kinetic parameters in CAPD patients. AB - This study reports on the five years' evolution of the KT/V urea index and protein catabolic rate (PCR) in 16 CAPD patients who were treated with a constant daily dialysis dose. Total KT/V urea index decreased with time from a value of 0.96 +/- 0.06 at the start to 0.55 +/- 0.05 at five years of treatment. This decline was due to the opposite changes of two important parameters affecting the index. First, the contribution of the residual urinary KT/V gradually decreased from 28.6% at the start to 8 to 9% after four years. Second, the distribution volume of urea calculated as a constant fraction of body weight gradually increased. The body weight increased from 58.2 +/- 2.79 kg at start to 70.6 +/- 3.33 kg at five years. Peritoneal urea clearances and ultrafiltration rates remained stable. In 12 patients with stable body weight between 24 and 48 months, PCR decreased from 0.98 +/- 0.05 to 0.87 +/- 0.05 g/kg/day. A positive correlation between KT/V urea and PCR and a negative correlation between KT/V urea and number of hospitalization days, peritonitis rates and peripheral nerve conductivity was found. The same negative correlation was found when only the KT/V urea index obtained during the first year of treatment was considered. In conclusion, the KT/V urea index decreases in CAPD patients primarily because residual renal function decreases and body weight increases, while the peritoneal clearing for urea is maintained. The index correlates with some clinical parameters, and may have some prognostic value. PMID- 1405327 TI - Prazosin attenuates the natriuretic response to atrial natriuretic factor in man. AB - The effect of alpha-1-adrenoceptor blockade with 0.25 mg oral prazosin on the renal response to atrial natriuretic factor (ANF) 5 pmol/kg/min was examined in eight healthy male volunteers undergoing maximal water diuresis. ANF on its own decreased mean arterial blood pressure (P less than 0.05) without altering heart rate or increasing plasma norepinephrine. ANF increased urinary sodium excretion by 130% (P less than 0.01) from baseline value with accompanying 18% decrease (P less than 0.05) in PAH clearance (ERPF) without changing inulin clearance (GFR). When compared to placebo infusion, ANF infusion caused a significant increase in fractional excretion lithium (FELi), a marker of proximal tubular function. Fractional distal delivery of sodium, another marker of proximal tubular outflow as determined by free water clearance, was also increased during ANF infusion. As expected, ANF decreased distal nephron fractional sodium reabsorption as evaluated by both the "lithium method" and by the conventional "solute-free water method." Prazosin on its own had no effect on blood pressure, renal function or hormonal parameters. When given in combination with ANF, prazosin blunted the natriuretic effect of ANF from 130% to 35% (P less than 0.01). However, prazosin pretreatment did not influence the ANF-induced fall in blood pressure or ERPF nor the ANF-induced suppression of plasma aldosterone. We have therefore found evidence to support the hypothesis that at basal levels of sympathetic tone, the natriuretic effect of ANF in man is dependent on an intact sympathetic nervous system, since sympathetic blockade by prazosin blunts its sodium excretory effects. PMID- 1405328 TI - Effect of dialyzer geometry during hemodialysis with cuprophane membranes. AB - The effect of dialyzer geometry, both flat plate (FP) and hollow fiber (HF), on platelet and granulocyte activation during dialysis with cuprophane membranes was studied in 12 patients. A subset of six patients was restudied after correction of their anemia with recombinant human erythropoietin (EPO). Granulocyte count and aggregation in vitro fell significantly (P less than 0.01) at 20 minutes of dialysis, followed by a gradual return towards pre-dialysis values at 240 minutes. Malondialdehyde (MDA), a product of free radical reactions generated by activated granulocytes, increased significantly during dialysis [predialysis MDA (median, range): 8.4 (5.8 to 11.6) nmol/ml, 240 minutes MDA: 9.7 (6.6 to 12.5) nmol/ml, P less than 0.01 Wilcoxon test). This increase, however, was not affected by dialyzer geometry or EPO therapy. Neither type of dialyzer was associated with significant platelet loss at the end of dialysis. Whole blood platelet aggregation in vitro (spontaneous and collagen-induced) decreased significantly, (P less than 0.01) during dialysis, the fall in spontaneous aggregation being significantly less following EPO therapy [spontaneous aggregation 240 minutes; pre-EPO: 34 (13 to 52)%; post-EPO 50: (16 to 76)%, P less than 0.01)]. The ratio of the platelet release proteins beta-thromboglobulin and platelet factor 4 increased significantly during dialysis, indicating platelet activation in vivo, although there was no effect of dialyzer geometry or EPO. Factor VIII von Willebrand Factor antigen, a putative marker of endothelial damage, was raised pre-dialysis, and increased further during dialysis, irrespective of dialyzer geometry or EPO. In conclusion, dialyzer geometry had no significant effect on granulocyte and platelet counts and activity during hemodialysis with cuprophane membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405329 TI - Continuous arteriovenous hemodialysis: effect of dialyzer geometry. PMID- 1405330 TI - Long-term comparison between captopril and nifedipine in the progression of renal insufficiency. AB - To verify the hypothesis that angiotensin-converting enzyme (ACE) inhibitors possess a unique renoprotective effect in progressive chronic renal disease, we decided to compare the effects of an ACE inhibitor and a calcium antagonist on both hypertension and the progression of non-diabetic renal insufficiency in a long-term study. A four-year, multicenter, prospective, randomized trial was conducted on 142 hypertensive patients (pts) with established chronic renal failure from six Italian nephrology departments. They were on standard antihypertensive therapy with a low-protein diet and underwent twice-monthly surveillance for a one year pre-randomization period. After that year, 121 pts were randomly allocated to captopril or slow-release nifedipine therapies for a three-year study period. The progression of renal insufficiency was monitored every two months. Blood pressure control was significantly better after randomization than during the year of standard antihypertensive therapy. The progression rate before randomization (BR) was definitely higher before than after randomization (AR): Creatinine clearance (CCr) change BR = -0.46 +/- 0.45 ml/min/month, creatinine clearance change AR = -0.23 +/- 0.43 ml/min/month (P less than 0.01). After randomization, the mean blood pressure values were virtually the same throughout the three year period of the study in the two groups treated by captopril (group I), or nifedipine (group II).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405331 TI - ACE inhibitors in renal disease. PMID- 1405332 TI - Forefronts in nephrology: summary of the newer aspects of renal cell injury. PMID- 1405333 TI - Adequacy of dialysis: a critical analysis. PMID- 1405334 TI - Cytokine regulation of adenylate cyclase activity in LLC-PK1 cells. AB - Although several cytokines have been demonstrated to exert pleiotropic responses, there is little information on cytokine regulation of renal tubular epithelial cell function. In the present studies, we find that both T cell-derived (tumor necrosis factor-beta and interleukins 2 and 3) and monocyte/macrophage derived (tumor necrosis factor alpha and interleukin 1 beta) cytokines promote basal, arginine vasopressin- and forskolin-stimulated adenylate cyclase activity in cultured LLC-PK1 cells. No effect of TNF, IL-1 beta, and IL-2 to stimulate protein kinase C activity was observed. TNF-beta, IL-1 beta and IL-2 also modestly stimulated 3H release from 3H-arachidonic acid labeled cells. Mepacrine, a phospholipase A inhibitor, prevented TNF-beta stimulation of 3H release from 3H arachidonic acid labeled cells and TNF-beta potentiation of adenylate cyclase activity. TNF-beta potentiation of adenylate cyclase activity and stimulation of 3H release from 3H arachidonic acid labeled cells was not prevented by pertussis toxin. These results demonstrate that several cytokines can stimulate adenylate cyclase activity while not affecting protein kinase C activity in cultured renal tubular epithelial cells. The effect of TNF-beta to stimulate adenylate cyclase appears to occur independent of pertussis toxin-sensitive substrate and may involve activation of phospholipase A. PMID- 1405335 TI - Glomerular hemodynamics and hormonal evaluation during starvation in rats. AB - The effects of total food deprivation on renal function were evaluated in normal Munich-Wistar rats submitted to starvation (S) periods of two to eight days (Groups S2 to S8). A prompt and sustained decrease in renal plasma flow (RPF) and an increase in total renal vascular resistance (TRVR) were observed after the second day, together with a gradual decrease in glomerular filtration rate (GFR) until the fourth day (40% in the S4 group, P less than 0.05). After this period, a spontaneous and progressive increase in GFR occurred in spite of continuing low RPF and high TRVR. Glomerular hemodynamics were evaluated in additional animals from groups S4 and S7. As observed for whole kidney GFR, mean single nephron (SN) GFR was reduced in group S4, but not in group S7. The decline in SNGFR in S4 was the result of a decline (approximately 40%) in glomerular plasma flow rate (QA) and glomerular capillary hydraulic pressure (PGC), due to a predominant increase (approximately 60%) in afferent arteriolar resistance. In S7, SNGFR and its determinants did not differ from the control. Angiotensin II (Ang II), prostaglandin (but not thromboxane A2, TxA2) inhibition blunted the alterations in whole kidney function observed in S4. Conversely in S7, the inhibition of vasoconstrictor agents (Ang II and TxA2) did not normalize GFR, suggesting that the intrarenal vasoconstriction could be an important factor to maintain GFR after a prolonged period of starvation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405336 TI - Metabolic effects of 4-pentenoate on isolated dog kidney tubules. AB - The effects of 4-pentenoate (0.01 to 10 mM) were studied on suspensions of cortical tubules and of thick ascending limbs (TAL) prepared from dog kidneys. When cortical tubules were incubated with 1 mM glutamine, 4-pentenoate accelerated glutamine uptake, ammoniagenesis, and the production of alpha ketoglutarate, lactate and pyruvate, but decreased gluconeogenesis. With 5 mM glutamine, the marked accumulation of alpha-ketoglutarate reversed the net fluxes through the alanine and aspartate aminotransferases. When cortical tubules or TAL were incubated with lactate, its utilization and gluconeogenesis (in cortical tubules) were markedly decreased by 4-pentenoate. The mitochondrial NAD+/NADH ratio was markedly increased by 4-pentenoate in cortical tubules but not in TAL. The production of 14CO2 from 14C[1]-pyruvate or 14C-[1]-alpha-ketoglutarate was decreased by approximately 60% by 4-pentenoate in cortical tubules but not in TAL. In cortical tubules, these findings are best explained by depletion of mitochondrial free CoA, inhibition of pyruvate and alpha-ketoglutarate dehydrogenases and decreased mitochondrial NADH. By contrast, in TAL, accumulation of reducing equivalents probably resulted from the metabolism of 4 pentenoate itself. PMID- 1405337 TI - Influence of ammonia and pH on protein and amino acid metabolism in LLC-PK1 cells. AB - Metabolic acidosis inhibits protein synthesis (PS) and stimulates protein degradation (PD) in muscle and cultured myocytes but causes hypertrophy of the proximal tubule. The reason for this tissue-specific difference in response to acidosis is unknown, but it might be related to stimulation of renal ammonia production since ammonia reportedly increases PS and inhibits PD in cultured kidney cells. We examined how ammonia and pH could interact to change protein turnover in confluent LLC-PK1 cells. Varying extracellular pH from 6.95 to 7.60 did not alter PS or PD even though intracellular pH changed predictably. Six millimolar NH4Cl did not change PS while 20 mM inhibited PS; there was no interaction with pH. This unexpected difference from the reported stimulation of PS by NH4Cl could be explained by our use of L-[U-14C]phenylalanine rather than radiolabelled leucine to measure PS. NH4Cl was found to inhibit leucine degradation which would increase radiolabelled leucine available for incorporation into protein. Either 6 mM or 20 mM NH4Cl inhibited PD measured as the release of L-[14C]phenylalanine from prelabelled protein. Experiments with an inhibitor of lysosomal function, chloroquine, suggest that NH4Cl inhibits lysosomal proteolysis. There was no interaction of cell pH and ammonia-induced changes in PD. Thus, the response of renal cells to acidification differs markedly from myocytes and ammonia changes protein turnover primarily by suppressing PD. PMID- 1405338 TI - Decreased O2 consumption by PMNL from humans and rats with CRF: role of secondary hyperparathyroidism. AB - Bactericidal ability of polymorphonuclear leukocytes (PMNL) is impaired in chronic renal failure (CRF). This function of PMNL is mediated by the generation of oxidizing radicals and the latter event requires O2 consumption by these cells. The present study examined both basal and FMLP-stimulated rise in cytosolic calcium ([Ca2+]i) and O2 consumption of PMNL from normal subjects and hemodialysis patients and from CRF rats, and evaluated the potential role of secondary hyperparathyroidism of CRF on these properties of PMNL. Basal levels of [Ca2+]i were significantly higher, and FMLP-induced increments in [Ca2+]i were significantly lower in PMNL of both humans and rats with CRF than in normals. Basal and FMLP-stimulated O2 consumption were significantly lower in CRF subjects and rats than in normals. These derangements were prevented by prior parathyroidectomy of CRF rats or by their treatment with verapamil from day one of CRF. Also, therapy of rats with pre-existing CRF with this drug reversed the abnormalities in [Ca2+]i and in O2 consumption of PMNL. The data indicate that: (1) CRF is associated with derangements in the homeostasis of [Ca2+]i of PMNL and their oxygen consumption, (2) these abnormalities are, most likely, mediated by the state of secondary hyperparathyroidism of CRF, and (3) verapamil, which blocks the PTH-induced entry of calcium into cells, and prevents as well as reverses these PMNL dysfunctions. These results implicate the excess PTH of CRF in the genesis of the defective bactericidal function of PMNL, and assign a new dimension to PTH toxicity in CRF. PMID- 1405339 TI - Mild renal ischemia activates primed neutrophils to cause acute renal failure. AB - The role of neutrophils (PMN) in acute renal failure (ARF) is controversial. Although the development of acute renal failure (ARF) frequently occurs in situations where there is partial activation of PMN (primed PMN) and mild renal ischemia, the interaction between primed PMN and ischemic organs has not been studied in any biological system. To define the interaction between primed PMN and mild renal ischemia, kidneys were made ischemic for 10 minutes in situ and reperfused by the isolated kidney technique with untreated PMN or PMN primed with low concentrations of lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). We found that primed PMN had no effect on control (non-ischemic) kidneys and that untreated PMN did not cause injury to kidneys previously subjected to mild ischemia. However, addition of primed PMN to mildly ischemic kidneys caused severe injury. To determine the nature of renal injury, ischemic kidneys were reperfused with primed PMN and catalase (CAT) or the elastase inhibitor, Eglin C. In ischemic kidneys reperfused with LPS-primed PMN, Eglin C (but not CAT) was partially protective while in ischemic kidneys reperfused with PMA-primed PMN, CAT (but not Eglin C) was partially protective. Reperfusion with both CAT and Eglin C completely prevented the damaging effects of either LPS- or PMA-primed PMN. In conclusion, addition of primed but not untreated PMN causes ARF in mildly ischemic kidneys by PMN oxidant- and/or protease-mediated mechanisms. This synergism could account for the high frequency of ARF in conditions associated with prerenal azotemia and primed PMN. PMID- 1405340 TI - Ontogeny of aromatic L-amino acid decarboxylase-containing tubule cells in rat kidney. AB - Dopamine plays an important role in regulation of renal sodium transport. Proximal tubule cells produce dopamine after decarboxylation of L-DOPA via the enzyme aromatic L-amino acid decarboxylase (AADC). The presence and cellular localization of AADC-like immunoreactivity (-LI) and AADC mRNA were examined during pre- and postnatal development in rat kidney by indirect immunofluorescence and in situ hybridization histochemistry. Few scattered condensations of AADC-immunoreactive (-IR) tubule cells forming a lumen were detected on gestational day 18. From gestational day 21, many AADC-IR tubule cells were observed in the inner cortex, whereas the outer cortex lacked AADC-LI. Within 24 hours of birth, AADC-IR cells in the inner cortex could be identified as proximal tubule cells. During day 3 and 5 there was an increase in number of AADC-IR proximal tubule cells in the inner cortex, leaving less amount of AADC negative cells in the outer cortex. Starting from day 8, AADC-IR cells could be seen in the outer cortex. An apparent decrease in AADC-immunofluorescence intensity was observed at 40 days, and at 80 days virtually no AADC-LI could be demonstrated. Intrarenal levels of dopamine showed a tendency to increase between 3 and 20 days, and showed significant decreases between 20 to 40 days and between 40 to 80 days. AADC mRNA was not detected in the kidney at 18 hours after birth, but could be observed in the inner cortex at 6 days. At 12, 19 and 40 days AADC mRNA was seen in the entire cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405341 TI - Renal function after release of ureteral obstruction: role of endothelin and the renal artery endothelium. AB - Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) are decreased and mean arterial pressure (MAP) is increased after unilateral release of bilateral ureteral obstruction (BUO). An imbalance between vasoconstrictor and vasodilator substances may explain the hemodynamic alterations seen in this setting. The present study examines the role of endothelin-1 in such alterations. Rats with BUO (N = 10) had significantly lower GFR and ERPF (ml/min/kg body wt) than sham-operated rats (SOR, N = 9) (1.40 +/- 0.14 vs. 6.20 +/- 0.38 and 5.12 +/ 0.68 vs. 20.2 +/- 2.20, respectively) and significantly higher MAP (mm Hg) than SOR (154.9 +/- 3.2 vs. 120.6 +/- 1.7). Rats with BUO given a specific antiendothelin antibody (N = 8) had significantly higher GFR (2.10 +/- 0.12) and ERPF (7.46 +/- 0.95) than BUO control rats, but there were no significant changes in MAP (159.5 +/- 5.8). In SOR (N = 6), mechanical denudation of the main renal artery endothelium did not significantly affect renal function when compared to renal function in control SOR. However, the same maneuver significantly lowered GFR (0.64 +/- 0.17) and ERPF (1.67 +/- 0.36) in BUO rats (N = 5) when compared to BUO control rats. We conclude that: (1) endothelin-1 has a significant vasoconstrictor role in rats with BUO of 24 hours duration and accounts for a portion of the decrease in glomerular filtration rate seen in rats after unilateral release of bilateral ureteral obstruction, and (2) in the BUO setting, the net role of the renal artery endothelium is vasodilatory. PMID- 1405342 TI - A new method to localize active renin in tissues by autoradiography: application to dog kidney. AB - A method was developed to localize active renin in dog kidney sections using autoradiography to detect in vitro binding of the radiolabeled renin inhibitor, 125I-H77. Light fixation by prior perfusion of the kidney with paraformaldehyde was used to immobilize renin without denaturing its binding activity. Snap frozen sections were cut on a cryostat and incubated with 125I-H77. Dry film autoradiography revealed discrete binding of 125I-H77 to the vascular pole of glomerulus as well as diffuse binding to the outer medulla and to the cortex. Binding of 125I-H77 to other aspartyl proteases in the latter two regions was then suppressed by addition of the aspartyl protease inhibitor, N-acetyl pepstatin (1 microM). This revealed only the juxtaglomerular binding and successfully suppressed binding of the radioligand to other sites. Light microscopic emulsion autoradiography revealed highly selective discrete labelling of the juxtaglomerular apparatus. Competition for this 125I-H77 binding by a series of structurally different renin inhibitors showed a close correspondence between their reported inhibitory potency for renin and potency in the binding system. This strongly suggests that the radioligand binds to the active site of renin immobilized in the kidney. These results demonstrate a new method to localize active renin in tissues using in vitro autoradiography and radioinhibitor binding. The method shows promise for localization and quantitation of tissue renin in extra renal tissues. PMID- 1405343 TI - Outcome of renal transplantation in children less than two years of age. AB - Twenty-two renal transplants were performed in 21 children less than two years of age at Children's Hospital. Fourteen were from living related donors and eight were from cadaveric donors. The five year patient and graft survivals of these recipients were compared to all other pediatric recipients between two and 18 years of age who received renal transplants over the same time period. Five year graft survival for recipients less than two years of age was 86% following living related donor transplantation and 38% following cadaver donor transplantation. Older pediatric recipients aged between two and 18 years had a five year graft survival of 73% following living-related donor renal transplantation, which was similar to that for recipients less than two years of age. Although older cadaveric recipients had a comparable five year graft survival to younger recipients, at 42%, the patterns of graft loss were different. Graft failures in young recipients occurred within the first seven months post-transplant, whereas the older recipient's grafts failed more gradually. Actuarial five-year patient survival in recipients less than two years of age was 86% following living related donor renal transplantation and 70% following cadaver-donor renal transplantation. Recipients less than two years of age had a poorer patient survival than older recipients following both living-related donor renal transplantation (P = 0.06) and cadaver-donor renal transplantation (P less than 0.05). These findings suggest that the graft survival of living-related donor renal transplantation in recipients less than two years of age is better than that of cadaver-donor renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405344 TI - Recombinant human erythropoietin treatment improves platelet function in uremic patients. AB - The effect of recombinant human erythropoietin (rHuEPO) on primary hemostasis was tested in 19 hemodialyzed patients. Bleeding time, platelet aggregation and platelet interaction with vessel subendothelium (SE) under flow conditions were determined before treatment and after patients reached hematocrits greater than or equal to 30%. Two thrombotic events (an acute myocardial infarction and an AV fistula clotting) were recorded during the early stages of treatment. A shortening of average bleeding times (P less than 0.01), an increase in platelet count (P less than 0.01) and an improvement of platelet aggregation (P less than 0.01) and of platelet-SE interaction (P less than 0.01) were observed. A low correlation index was found between hematocrit and bleeding time (r = -0.351, P less than 0.05). To assess a possible effect of rHuEPO on platelet function, the same parameters were evaluated before and after receiving three doses of rHuEPO (40 U/kg i.v. post-hemodialysis) in 14 of the patients. No changes in platelet or erythrocyte counts were observed, the mean bleeding time remained unchanged, but platelet aggregation induced by arachidonic acid (P less than 0.05), ADP (P less than 0.01) and ristocetin (P less than 0.05) improved. Perfusion studies confirmed moderate but significant increases in the parameters that quantify platelet-SE interaction (P less than 0.05). Improvement of ADP-induced aggregation correlated with the increase of platelet adhesion to SE (r = 0.675, P less than 0.05). We conclude that rHuEPO treatment improves primary hemostasis in uremia through an increase of red cell mass but also through a beneficial effect on platelet function, which is independent of the hematocrit rise. PMID- 1405345 TI - Role of inhibition of atrial natriuretic factor release in the down-regulation of salt excretion. AB - We investigated the role of atrial natriuretic factor (ANF) in the down regulation of sodium excretion (UNaV). Seven subjects were sequentially studied while ingesting a normal-salt diet (220 mmol NaCl/day, NSD), a very low-salt diet (20 mmol NaCl/day, VLSD) for six days, and again at NSD for nine days. After one day of VLSD, a negative salt balance of 85 mmol was achieved and plasma ANF decreased from 19.1 (SE 2.5) to 7.2 (SE 2.1) pg/ml, whereas plasma renin activity (PRA) and plasma aldosterone (ALD) increased after the third and second day, respectively. During restoration of volemia (NSD), ANF increased after the third day; in contrast, PRA and ALD decreased earlier. Seven other subjects kept at low salt diet (50 mmol NaCl/day) were studied during ANF infusion (at 2, 4, 8 ng/min/kg body wt). Increases of ANF from 10.3 (SE 0.9) pg/ml (basal condition) to levels of 24.0 (SE 1.9) pg/ml (infusion study), occurring physiologically in the same subjects after NSD, evoked increases in UNa V that accounted for 62% of UNa V rise necessary to balance the NSD, whereas PRA or ALD did not change. Plasma ANF, unlike PRA or ALD, was directly correlated with UNa V. IN CONCLUSION: (a) ANF changes earlier than PRA and plasma aldosterone during VLSD; (b) PRA and ALD respond more promptly than ANF in the recovery from hypovolemia; (c) during ingestion of a low-salt diet, changes in plasma ANF by infusion account for more than half the increase in UNa V following the shift from low- to normal-salt diet independently of alterations in PRA and ALD. PMID- 1405346 TI - Uremic serum effects on peripheral blood mononuclear cell and purified T lymphocyte responses. AB - We have studied the effects of uremic serum on the activation state and function of normal lymphocytes in vitro, by examining both accessory cell-dependent and accessory cell-independent responses. Uremic serum was obtained from patients on conservative treatment and from the same patients after they have undergone six months of maintenance hemodialysis. Uremic serum inhibited the proliferative responses to mitogens and to recombinant IL-2 (rIL-2) of both peripheral blood mononuclear cells (PBMC) and purified T cell populations. However, the responsiveness to IL-2 of pre-formed lymphoblasts, obtained from both PBMC and purified T cells, in the presence of uremic serum was similar to that obtained in the presence of normal serum, or was even enhanced. Uremic serum did not affect the cellular IL-2 receptor alpha (IL-2R) generation though it inhibited significantly the release of soluble IL-2 receptor (sIL-2R) and the production of IL-2 after mitogenic stimulation. Uremic serum from patients after six months of hemodialysis enhanced, but did not completely restore, proliferative responses and IL-2 production by control PBMC. Neither IL-1 nor IL-2R, which are present at elevated concentrations in uremic serum, appeared to be responsible for serum effects on in vitro responses of control lymphocytes. In conclusion, our results indicate that uremic serum affects both accessory cell-mediated and accessory cell-independent normal T cell responses. Uremic serum inhibition of T cell proliferation is associated with down-regulation of IL-2 synthesis by lymphocytes and the induction of an abnormal state of activation of lymphoblasts which is further enhanced following chronic hemodialysis. PMID- 1405347 TI - A monoclonal antibody (1G10) recognizes a novel human mesangial antigen. AB - We have identified a unique mesangial matrix protein of the human glomerulus by using a monoclonal antibody, 1G10, generated against culture human glomerular cells. By immunofluorescence, the antigen recognized by 1G10 (1G10 antigen) is present in mesangium and smooth muscle tissue and cannot be detected in any other tissue examined. Immunoelectron microscopy of glomeruli indicated that 1G10 antigen is present exclusively in the mesangial matrix at the endothelial mesangial interface. The 1G10 antigen is also expressed by cultured mesangial cells, but not by cultured glomerular epithelial cells, umbilical endothelial cells or fibroblasts. 1G10 did not react with the mesangial matrix proteins [fibronectin (FN), laminin (LAM), collagen types I, III, IV, V, and VI (Col I, III, IV, V, VI), heparin sulfate proteoglycan (HSPG), or thrombospondin (TS)] present under normal and diseased states or smooth muscle antigens (myosin, actin), but did react with a 4 M urea extract of renal cortex and a 0.3% deoxycholate extract of isolated glomeruli. Two dimensional immunoblot analysis using the urea extract demonstrated the binding of 1G10 to an approximately 200 KDa polypeptide with pI 6.0. On one dimensional immunoblot this band did not show cross react with polyclonal antisera to FN, LAM, Col IV, V, VI, HSPG or TS. This mesangial matrix component is trypsin and periodate sensitive, suggesting that it has the character of glycoprotein. In renal biopsy specimens from patients with mesangial proliferative glomerulonephritis (GN) and membranoproliferative GN, the expression of the 1G10 antigen increased along with mesangial hypercellularity or increased accumulation of mesangial matrix, but decreased in completely sclerosed glomeruli. No significant changes in 1G10 antigen expression was observed in membranous GN or minimal change nephrosis compared to normal glomeruli. This study suggests that the 1G10 antigen may not only be a useful marker for the clinical assessment of GN, but may also serve as a potential tool for the study of the pathogenesis of glomerular diseases characterized by cellular proliferation and mesangial matrix expansion. PMID- 1405348 TI - Differential effects of calorie restriction on glomeruli and tubules of the remnant kidney. AB - We have previously shown that 40% calorie restriction (CR) prevents renal injury 21 weeks after 5/6 nephrectomy (Nx) in rats, regardless of whether protein intake was concurrently restricted or not. Growth retardation appeared to be a necessary prerequisite for the protective effects of CR. To further study these mechanisms, we performed 5/6 Nx in male F344 rats and pair-fed them with a control diet (ad lib group) or a high protein diet restricted by 40% so that protein intake was similar, but calorie consumption was reduced (CR group). Four weeks after 5/6 Nx, when glomerulosclerosis had not yet developed, we compared various parameters as follows in both dietary groups and sham operated rats: urinary protein excretion (uPr), GFR (14C inulin clearance), mean nephron GFR (MNGFR; GFR divided by total number of glomeruli), glomerular volume (VG), tubulointerstitial index (TII), a measure of tubular damage kidney weight (kidney wt), kidney IGF-I content by RIA, and IGF-I immunohistochemistry. CR ameliorated the increase of MNGFR, but not glomerular hypertrophy. TII, kidney wt and kidney IGF-I content were increased in the ad lib Nx group; these changes were alleviated by CR. Two weeks after 5/6 Nx, immunohistochemistry for IGF-I showed increased staining in superficial distal nephrons in the ad lib group, and this was also suppressed by CR. The occurrence of tubulointerstitial pathology prior to glomerulosclerosis, and the beneficial effects of CR on all parameters except Vg indicate a dissociation of mechanisms which result in tubular versus glomerular hypertrophy and damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405350 TI - Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans. AB - The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a six day eucapnic recovery period (500 m) under metabolic balance conditions. Chronic respiratory alkalosis (delta PaCO2, -8.4 mm Hg, delta[H+] -3.2 nmol/liter) resulted in a sustained decrement in plasma ionized calcium concentration (delta[IoCa++]p, -0.10 mmol/liter, P less than 0.05) and a sustained increment in plasma phosphate concentration (delta[PO4]p, +0.14 mmol/liter, P less than 0.005) associated with increased fractional excretion of Ca++ (+0.5%, P less than 0.005), decreased phosphate clearance (-6.1 ml/min, P less than 0.025) and decreased excretion of nephrogenous cAMP (-1.5 nmol/100 ml GFR, P less than 0.0025). Urinary phosphate excretion decreased by 15.4 mmol/24 hr on day 1 of chronic respiratory alkalosis (P less than 0.0025), but returned to control values by day 6 despite hyperphosphatemia. Serum intact [PTH] did not change. Sustained hypomagnesuria (-0.8 mmol/24 hr, P less than 0.05) occurred during chronic respiratory alkalosis and was accounted for, at least in part, by decreased fractional excretion of Mg++ (-0.7%, P less than 0.05) in the absence of change in plasma magnesium concentration. Serum 1,25(OH)2D levels were unchanged by chronic respiratory alkalosis. In conclusion, the decrease in nephrogenous cAMP generation despite unchanged serum intact PTH concentration suggests that chronic respiratory alkalosis results in impaired renal responsiveness to PTH as manifested by alterations in PTH-dependent renal calcium and phosphate transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405349 TI - Role of the venous system in hemodynamics during ultrafiltration and bicarbonate dialysis. AB - A reduced venous compliance (VC) and inadequate venoconstriction may impair hemodynamics during hemodialysis, the first by impairing plasma volume preservation and by inducing a steep fall in central venous pressure (CVP) during minor plasma volume loss, the second by inadequate mobilization of hemodynamically inactive blood volume. For the protocol A, the relation between VC, the fall in plasma volume and the decline in central venous pressure (CVP) was assessed in 12 hemodialysis (HD) patients, aged 40 to 74 years, during isolated ultrafiltration (UF). The patients were ultrafiltrated for one hour at an UF rate of 1 to 1.5 liter/hr. VC was measured by strain gauge plethysmography with direct i.v. pressure measurements. CVP was assessed directly via a subclavian catheter. PVP was measured using the serial hematocrit method. VC correlated inversely with the fall in plasma volume (r = -0.66; P less than 0.025) and with the fall in CVP (corrected for UF volume) (r = -0.62; P less than 0.025). In the protocol B, the constriction of veins and resistance vessels was assessed sequentially during isolated UF and during UF combined with bicarbonate HD (UF + HD) by measuring the change in venous tone (VT) and vascular resistance (FVR) of the forearm. Twelve HD patients were studied (age 30 to 64 years). VT and FVR were measured using strain gauge plethysmography. The UF rate was equal during isolated UF and UF + HD (1 liter/hr). In six patients, the measurements were started with isolated UF and in six patients with UF + HD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405351 TI - Role of alpha 1-proteinase inhibitor in restraining peritoneal inflammation in CAPD patients. AB - The concentration and functional state of alpha 1-proteinase inhibitor (alpha 1 PI) may modulate the expression of peritoneal phlogosis by affecting the activity of proteases and synthesis of autacoids. alpha 1-PI is detectable in peritoneal effluents of peritonitis-free patients. alpha 1-PI purified from peritoneal fluid of these patients was biologically active both in terms of inhibition of elastase activity and of synthesis of platelet activating factor (PAF). The biological activity of alpha 1-PI could therefore explain the absence of detectable amounts of PAF in peritonitis free patients despite the presence of intraperitoneal concentrations of tumor necrosis factor-alpha (TNF alpha) that would be sufficient per se to induce the synthesis of PAF. In patients with acute infectious peritonitis, the concentration of immunoreactive alpha 1-PI was significantly increased in respect ot stable patients. However, alpha 1-PI purified from patients with acute peritonitis was functionally inactive both on proteolytic activity on elastase and on TNF alpha-induced PAF synthesis by purified human PMN. The loss of alpha 1-PI activity correlated with the number of peritoneal leukocytes and was probably dependent on oxidative inactivation. Indeed, treatment with reducing agent restored the inhibitory function of alpha 1 PI. The inactivation of alpha 1-PI in patients with peritonitis was associated with the presence of PAF in peritoneal dialysates. These results suggest that alpha 1-PI prevents the proteolytic action and cell activation leading to PAF synthesis in peritonitis free patients. However, inactivation of its function by oxidants generated during the inflammatory process may lead to proteolytic injury and unrestrained synthesis of inflammatory mediators during peritonitis. PMID- 1405352 TI - Role of pathology indices in the management of severe lupus glomerulonephritis. Lupus Nephritis Collaborative Study Group. AB - The principal value of the renal biopsy in patients with SLE is as a therapeutic guide. Although semiquantitative indices of nephron loss (chronicity = CI) and acute potentially reversible inflammation (activity = AI) are reported by some to have separate values from traditional classifications of glomerular pathology as predictors of outcome and therapeutic guides, this point remains controversial. We have tested the predictive value of the AI and CI in a large group of patients with severe lupus glomerulonephritis (SLE GN) and a mean follow-up of 281 weeks +/- 116 (mean +/- SD). A total of 86 patients entered into the study of plasmapheresis in severe SLE GN by the Lupus Nephritis Collaborative Study Group, and long-term follow-up was available in 83. The predictive value of the AI and the CI was described over the entire range of cut-off points by the method of receiver operator characteristics (ROC). ROC analysis demonstrated that there was no level of either AI or CI that predicted the outcome of death or renal failure with sufficient sensitivity and specificity to be useful in the individual patient. The CI signifies renal damage and nephron loss, whereas the AI describes potentially reversible pathology. Neither the CI nor the AI taken by itself predicts individual outcomes of renal failure or death in patients with aggressively treated SLE GN. Since the indices fail to identify the patient whose disease will progress to renal failure, they are both insufficient as therapeutic guides and add little to the management of the patient with severe SLE GN. PMID- 1405353 TI - Up-regulated MHC-class II expression and gamma-IFN and soluble IL-2R in lupus nephritis. AB - Expression of MHC-class II molecules (HLA-DR and -DQ), serum gamma-interferon (gamma-IFN) and soluble interleukin-2 receptor (sIL-2R) levels were studied in 35 Japanese patients with lupus nephritis (LN) to clarify intraglomerular cellular activation and cytokine involvement in human LN. In 11 normal kidney specimens, HLA-DR(Ia1) was noted in glomerular tufts, but HLA-DQ was either not or was faintly detected in glomeruli by the indirect immunofluorescence technique. HLA DR and -DQ were observed mainly on the surface of glomerular endothelial cells in 100% and 50% of 28 lupus kidney specimens except for necrotic or sclerotic lesions. HLA-DQ was expressed in a high incidence of 67%, 86% in patients with proliferative LN (WHO Class III-IV) and active lesions, respectively. Serum gamma IFN and sIL-2R levels were 1.2 +/- 0.2 U/ml and 190 +/- 24 U/ml (mean +/- SEM; N = 30) in normal controls, and elevated in patients with proliferative LN (4.1 +/- 1.0 U/ml, 383 +/- 81 U/ml, N = 25), especially with active lesions (6.2 +/- 1.5 U/ml, 500 +/- 110 U/ml, N = 14). Overall, glomerular lesions such as HLA-DQ expression, the activity index and leukocyte infiltration correlated positively with serum gamma-IFN levels (r = 0.55; P less than 0.01 for HLA-DQ, r = 0.68; P less than 0.001 for activity index, r = 0.38; P less than 0.05 for leukocyte infiltration), but not with serum sIL-2R levels, anti-DNA antibody titers and CH50 titers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405354 TI - A PCR method for the quantitative assessment of mRNA for laminin A, B1, and B2 chains. AB - Laminin, a basement membrane glycoprotein, is involved in the development of normal kidney and its dysregulation contributes to glomerulosclerosis in renal disease. Studies designed to assess the regulation of this molecule at the level of transcription have been hindered by the relatively low abundance of the mRNA, making standard techniques such as Northern hybridization and RNase protection difficult and inaccurate. In this report, we have utilized the polymerase chain reaction (PCR) to quantitate differences in laminin mRNA expression during normal development of the mouse kidney. We have constructed a synthetic template to be used as an internal standard for mRNA quantitative of laminin chains A, B1 and B2, and beta-actin. This DNA template can be used to generate complementary RNA which can be reverse transcribed and amplified simultaneously with 0.5 microgram of total cellular mRNA allowing for accurate and absolute quantitation of laminin mRNA by PCR. PMID- 1405355 TI - Endothelin receptor antagonism is protective in in vivo acute cyclosporine toxicity. AB - Endothelin (Et) has been implicated in cyclosporine A (CsA) nephrotoxicity. We have previously shown that CsA treatment in rats results in up-regulation of Et receptors specifically within the kidney. The role of Et in vivo CsA nephrotoxicity was therefore studied further with a new competitive antagonist, BQ-123, specific for Et(A) receptors (EtRA). Systemic administration of CsA in Munich-Wistar rats resulted in marked glomerular hypoperfusion and hypofiltration, with RPF in left and right kidneys falling by some 40% to 1.60 +/ 0.25 and 1.73 +/- 0.38 ml/min and GFR decreasing by some 20% to 0.61 +/- 0.05 and 0.67 +/- 0.11 ml/min, respectively. Selective infusion of EtRA into the left renal artery following systemic CsA treatment had no effect on this hemodynamic pattern (RPF 1.58 +/- 0.29 and 1.92 +/- 0.34 ml/min and GFR 0.60 +/- 0.09 and 0.70 +/- 0.08 ml/min in left and right kidneys, respectively, P = NS vs. CsA period). By contrast, intrarenal infusion of EtRA prior to systemic administration of CsA resulted in a strikingly different pattern of renal hemodynamics. Thus, EtRA pretreatment in the left kidney protected against glomerular dysfunction following CsA: RPF was maintained, 3.23 +/- 0.28 ml/min versus 2.96 +/- 0.31 (P = NS EtRA vs. EtRA + CsA), as was the GFR, 1.04 +/- 0.16 ml/min versus 1.12 +/- 0.09 (P = NS). However, the contralateral right kidneys of these rats, not pretreated with EtRA, showed no protective effect: RPF decreased from 3.15 +/- 0.34 ml/min to 2.39 +/- 0.19 and GFR from 1.04 +/- 0.10 ml/min to 0.85 +/- 0.07 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405356 TI - A mechanism of glycine and alanine cytoprotective action: stimulation of stress induced HSP70 mRNA. AB - Studies done both in vitro and in vivo have shown that glycine and alanine protect kidney cells from stress injury. However, the mechanism(s) of this cytoprotection is unknown. Our aim was to test the hypothesis that the cytoprotective action is in part due to stimulation of gene(s) expression encoding stress protein synthesis. Experiments were carried out using heat shock as a model for stress in the opossum kidney cell line (OK cells). The induction of HSP70 mRNA was evaluated in cell monolayers exposed to 45 degrees C for 15 minutes followed by a recovery period at 37 degrees C for either 0.5, 1, 2, 3, 4, 6 or 24 hours. The results demonstrate that the maximum level of HSP70 mRNA occurred at approximately three hours after heat treatment. Although the mRNA levels declined thereafter, appreciable amounts were still seen even 24 hours after heat-shock. To examine the effect of glycine or alanine on HSP70 mRNA levels and on the synthesis of stress protein, cultures were preincubated for 30 minutes with Krebs-Henseleit buffer, pH 7.4, supplemented with either 1, 2, 5 or 10 mM glycine or alanine, or with no added amino acids. Comparative studies were performed with 10 mM glutamate, aspartate, arginine or leucine. Following preincubation, cultures were heat-shocked (45 degrees C for 15 min) and then reincubated at 37 degrees C for three hours. Both glycine and alanine enhanced the level of HSP70 mRNA and the synthesis of 72, 73 kDa stress proteins, but neither amino acid induced HSP70 mRNA without concomitant heat treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405357 TI - Molecular genetics of hereditary nephritis. PMID- 1405358 TI - Jean Hamburger 1909-1992. PMID- 1405359 TI - 15-Lipoxygenase products as leukotriene antagonists: therapeutic potential in glomerulonephritis. AB - In the first few hours following immune complex deposition and complement mediated neutrophil (PMN) infiltration, glomerular generation rates of the arachidonate 5-lipoxygenase (5-LO) derivatives leukotrienes (LT) C4, D4, and B4 are stimulated markedly. These LTs exert effects on glomerular functions which include reduction in the glomerular ultrafiltration coefficient and glomerular filtration rates, exacerbation of proteinuria, and amplification of PMN-provoked glomerular damage through LTB4-induced PMN chemotaxis, adhesion, and activation. Following this early burst, glomerular LT synthesis is suppressed, macrophages replace PMNs, and glomerular generation of 15-S-hydroxyeicosatetraenoic acid [15 (S)-HETE], a 15-lipoxygenase derivative of arachidonic acid and a precursor molecule for lipoxin (LX) biosynthesis, increases progressively over the ensuing days to weeks. Here, we summarize evidence supporting the notion that the activation of the 15-LO pathway in the wake of early 5-LO activity is a specific counter-inflammatory signal which limits and antagonizes the proinflammatory actions of leukotrienes. PMID- 1405360 TI - Role of cellular metabolites in progressive renal injury. PMID- 1405361 TI - Clinical strategies for arresting progression of renal disease. AB - The incidence of end-stage renal disease is increasing and this results in an enhanced requirement of renal replacement therapy facilities. This brings about a significant burden on health care budgets and makes strategies that slow down or even prevent deterioration of the renal function mandatory. Although large scale randomized, controlled and prospective clinical trials on the effect of blood pressure control on the course of renal function are lacking, there is circumstantial evidence from animal, epidemiological and clinical studies to state that treatment of hypertension to blood pressure values well within the normal range is most important to ameliorate the downhill course of renal function in patients with chronic renal failure. Moreover, treatment of hypertension is critical to reduce morbidity and mortality of cardiovascular disease in these patients, who have an increased risk for such events. Low protein diets, if possible with ketoacid supplement, are advocated to slow down the deterioration of renal function. However, based on the results of recent studies, low-protein diets may only have a moderate effect in patients with diabetic nephropathy and, possibly, in patients with chronic glomerulonephritis. The possibility of influencing renal ammoniagenesis by protein restriction or calcium carbonate administration, and an attenuation of alternative complement pathway activation and tubulo-interstitial injury, are challenging. Finally, in animal studies it has been found that abnormalities in serum lipid profile contribute to the progression of chronic renal failure, which may be prevented by pharmacological treatment of hyperlipidemia. Studies in humans concerning this subject are lacking at this moment, but treatment of hyperlipidemia is proper to reduce cardiovascular events. PMID- 1405362 TI - Treatment of immunologically mediated glomerular disease. AB - Many immunologically mediated glomerular diseases can be successfully treated, but clinicians should be wary of unproven claims of efficacy, be cognizant of long-term deleterious effects of treatment, and should select patients with a careful eye on the natural history of the untreated disorder. It is hoped that as we gain a better understanding of the etiology and pathogenesis of the specific entities that a more rational form of therapy will emerge. The powerful tools of molecular biology and our better understanding of the inflammatory and scarring processes may provide new, highly effective and safe approaches to treatment. Like their predecessors, these approaches, however, will require very careful evaluation in human subjects by prospective controlled clinical trials. Even if we cannot favorably influence the immunological processes responsible for glomerular disease, attention to non-immunologic factors responsible for progression of disease, such as hypertension, may substantially slow the rate of progression of disease even in those patients whose fundamental disease process cannot be arrested or cured. PMID- 1405363 TI - Natriuretic peptides and the kidney: current concepts. AB - The field of study of natriuretic peptides becomes more complex as we enter the second decade since their discovery. The attractive hypothesis that a single peptide secreted by the atria could regulate the physiological responses to salt and water loading has proven simplistic. Rather the atrial natriuretic peptide story has opened the door on a whole family of peptides, secreted from the atria, the ventricles, the brain, and even the kidney itself, all working in concert to achieve this regulation. The regulation of renal function by natriuretic peptides is presumably the result of the integration of these different peptides effects. Thus while atrial derived NP circulates and has direct effects on the glomerulus, other sources of NP (such as the kidney) may be responsible for some of the tubular effects of NP. Further definition of the mechanisms of regulation of the kidney derived NP are needed before any further conclusions can be drawn. PMID- 1405364 TI - Is the aggressive management of hyperlipidemia in nephrotic syndrome mandatory? AB - The development of the nephrotic syndrome is associated with a lipid profile characterized by increased total and low density lipoprotein cholesterol. Although total high density lipoprotein (HDL) values may be in the normal range, there is frequently abnormalities of HDL subclasses, with reduction of the mature HDL2 subfraction. While these lipid changes may be considered a risk for atherosclerosis, they revert to normal with remission of the nephrotic syndrome. However, with chronic nephrotic range proteinuria, these abnormalities persist and may also be associated with increased levels of lipoprotein (a), increased levels of very light density lipoprotein and further reductions in HDL. These factors could all contribute to greater risk for atherosclerosis. Although coronary artery disease is frequently seen in patients with end-stage renal disease, and many uncontrolled studies in patients with chronic nephrotic syndrome have suggested an increased prevalence of cardiovascular disease, no prospective studies to evaluate relationship between lipid abnormalities and cardiac disease have been performed in patients with the nephrotic syndrome. Recent experimental data have also suggested a relationship between hyperlipidemia and progressive renal injury. Unfortunately, human epidemiological data are incomplete in correlating lipid changes with renal disease in patients with chronic nephrotic syndrome. No therapeutic trials have tested whether or not pharmacologic interventions will benefit either the cardiac or renal disease that ensues in patients with chronic persistent nephrotic syndrome. Thus, considerably more data are needed to help clarify this important area. PMID- 1405365 TI - Role of rHuEPO in treatment of uremic anemia prior to end-stage renal disease. PMID- 1405366 TI - What's new in peritoneal dialysis--an overview. AB - Patient survivals on continuous ambulatory peritoneal dialysis (CAPD) seem similar to survivals on hemodialysis (HD) in comparable populations. Technique survivals are improving on CAPD as peritonitis rates fall with the use of disconnect devices. Advances in catheter design and catheter care appear to be improving catheter survivals. The peritoneal membrane appears usable for many years provided that recurring peritonitis can be avoided. Mesothelial cell transplantation, low calcium solutions, and urea kinetic modeling are important new areas of interest with potentials to improve the therapy. Evidence continues to mount that residual renal function is better preserved in CAPD than in HD. PMID- 1405367 TI - Improved solutions for peritoneal dialysis: physiological calcium solutions, osmotic agents and buffers. AB - Theoretical and clinical studies suggest that reduction of PD fluid calcium to 1.25 mmol/liter allows administration of larger doses of calcium carbonate, improves phosphate control and obviates the need for aluminum gels in most CAPD patients, without increasing hypercalcemia or hyperparathyroidism. Hypermagnesemia can also be avoided by reducing PD fluid magnesium concentration to 0.25 mmol/liter. Although glucose is a safe, effective an cheap osmotic agent, it provides a short duration of ultrafiltration, and contributes to significant metabolic abnormalities. Amino acids and glucose polymer are potential alternatives to glucose, and early clinical studies are encouraging. The unphysiological concentration of lactate in PD fluids has been shown to have pathological consequences, and undoubtedly bicarbonate would be a preferable buffer. Manufacturing techniques are being developed to produce such a fluid. A fluid containing bicarbonate and the peptide glycylglycine (30:10 mmol/liter) gives a stable buffer with a pH of 7.35, but has only undergone animal studies so far. Glucose solutions have deleterious effects on the peritoneal membrane, particularly during episodes of severe peritonitis, and the high osmolality is toxic to peritoneal host defense cells. Prompt treatment of peritonitis, early removal of the catheter where necessary, and minimization of glucose exposure, may do much to lengthen the dialysis life of the peritoneum. PMID- 1405368 TI - The dose of hemodialysis according to dialysis prescription in Europe and the United States. AB - Prior research has shown that, controlling for age and diabetes, patients with end-stage renal disease in Europe generally have better rates of survival than do ESRD patients in the U.S. This analysis compares the dose of hemodialysis prescription in the two regions. Based on the European Dialysis and Transplant Association Registry (EDTA), the U.S. Renal Data System (USRDS), and other sources, European and U.S. ESRD patients were compared by demographic and anthropometric characteristics, dialyzer characteristics, and duration of dialysis treatment times. Average body weight and body mass indices were found to be similar for the ESRD populations of the two societies, suggesting the same overall requirements for dialysis therapy. During 1986 to 1988, dialyzers selected in Europe had a larger surface area by at least 20 percent compared to those selected in the U.S. In addition, duration of hemodialysis treatment times were on average 23.5% longer for EDTA patients. Dialyzer blood flows were not available for EDTA patients, but if EDTA blood flows resemble U.S. practices, total urea clearance per week was at least 29% higher in Europe than in the U.S. Combining similar patient characteristics with substantially greater total urea clearance per week, the hemodialysis prescription in Europe was substantially higher than in the U.S. for the time period of this study. PMID- 1405369 TI - Adequacy of CAPD: a quantitative approach. AB - In prescribing CAPD, general clinical practice is to use the standard regimen of 2L x 4 exchanges/day without regard to patient size, nutritional status, or residual kidney function. The standard regimen is usually adjusted in a trial and error manner reacting to clinical symptoms, life style issues, and patient compliance. The purpose of this paper is to recommend an alternative, quantitative approach based on urea kinetics that is prospective rather than reactive, and objective rather than subjective. The value of urea kinetic-based hemodialysis therapy prescription is well established and applying this knowledge to CAPD is a good starting point. The importance of small solute clearances for CAPD adequacy can be established on both theoretical and clinical grounds. The value of the KT/V urea index, its calculation, scaling factors for CAPD hemodialysis comparisons, and the correlation between KT/V and weekly creatinine clearances are examined. Residual renal function has a significant impact on small solute clearances, and failure to adjust the therapy prescription to compensate for declining residual kidney function will have a detrimental impact on KT/V and the protein catabolic rate. PMID- 1405370 TI - Nutritional aspects on peritoneal dialysis. AB - Peritoneal dialysis is associated with metabolic and nutritional abnormalities due to the combined effects of uremia per se, glucose absorption from the dialysate and a variety of catabolic factors, such as protein and amino acid losses into the dialysate, poor appetite possibly reflecting insufficient removal of small solutes, and recurrent episodes of peritonitis. Signs of protein-energy malnutrition are common, especially in patients with minimal or no residual renal function. Variables that best correlate with the degree of malnutrition include serum albumin, midarm muscle circumference, clinical signs of muscle wasting and loss of subcutaneous fat, and a history of anorexia. The incidence of malnutrition is higher in females than in males and in diabetics than in non diabetics. CAPD patients generally have a lower protein intake than HD patients, but may have a lower average protein requirement than HD patients. Progression of malnutrition may occur in CAPD patients due to the synergistic effects of loss of residual renal function, underdialysis, anorexia and inadequate dietary intake. In underdialyzed CAPD patients, the amount of dialysis should be increased and measures should be taken to increase the supply of energy and protein. The use of amino acid-based dialysis fluid may provide new opportunities for compensation of dialytic losses of protein and amino acids, normalization of essential amino acids, supplementation of inadequate dietary protein intake, and improvement of the nutritional status in CAPD patients. PMID- 1405371 TI - HLA matching effect on five-year graft survival and half-life in the cyclosporine era. AB - From 1984 to 1990, a 6 to 10% increase in one-year graft survival was noted for patients matched or mismatched for HLA A, B, or DR locus antigens. This improvement was not attributable to matching. In the cyclosporine era, five-year graft survival of 0-ABDR mismatched first cadaver donor transplants was 61% in contrast to 45% survival for the worst 6-antigen mismatched grafts. The long-term half-life of 0-ABDR mismatched grafts was 10.7 years, compared with 6.4 years for the 6-antigen mismatched transplants. The cumulative survival years (a measure of impact) were twice as high for 0-ADR, 0-BDR and 0-AB mismatched grafts compared with 0-ABDR mismatches. On the basis of cumulative survival, five-year survival, and half-life, one might suggest sharing kidneys for 1-2 ABDR mismatch, 1 BDR, 1 2 AB mismatch, and 1-ADR mismatch. Young patients (5 to 25 years old) had lower graft survival rates when receiving poorly mismatched grafts. HLA matching did not influence graft survival in Black recipients, whose half-lives were 3.8 to 4.6 years for all matching categories. PMID- 1405372 TI - How to deal with the hyperimmunized potential recipients. AB - End-stage renal disease (ESRD) patients with high levels of anti-HLA panel reactive antibodies (PRA) represent an increasing group in which sensitization, induced by pregnancies, previous transplants, and blood transfusions, considerably delay the opportunity to receive a graft. Currently, more than 50% of the 4700 patients awaiting transplantation in France are sensitized, of which 33% are defined as hyperimmunized (PRA greater than = 80%), and only 9.5% of the total number of transplants have been done in highly sensitized recipients. The magnitude of this problem, similar in Europe and North America, explains why more active strategies for managing hyperimmunized patients have been introduced during the past decade. Clearly, the simplest is finding of a well-matched organ that does not carry the HLA antigens against which the recipient has generated antibody, but that is limited by the number of shared grafts. The second is the development of a new cross-matching technique prior to transplantation. Attempts at immunoregulation of secreting B cell clones have been carried out using either hypertransfusions or injection of polyclonal Ig. Finally, removal and prevention of the resynthesis of HLA antibodies is a most attractive approach using immunoadsorption (IA) system with sepharose-bound protein-A columns. In our unit, fifteen ESRD patients with high levels of PRA were treated with IA. Infectious complications were not observed after IA and transplantation, and the procedure was well tolerated. In spite of the use of adjunctive immunosuppressive treatment with cyclophosphamide and prednisolone, this method produced only variable effects in lowering PRA levels, and was hampered by high de novo resynthesis of anti-HLA antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405373 TI - Antilymphocyte globulins in kidney transplantation. PMID- 1405374 TI - Kidney transplantation in diabetic patients: the University of Minnesota experience. PMID- 1405375 TI - New organ preservation solutions. AB - In 1969 we described a method for kidney preservation that used a brief flush with a new "intracellular" solution followed by ice storage. This paper stimulated research into optimizing solution composition culminating in the UW solution which is now the accepted standard. Further developments in the design of solutions for hypothermic organ preservation have proceeded along several paths, including: (1) modification and simplification of UW solution, (2) investigation of organ specific requirements, (3) addition of pharmacologic agents particularly calcium antagonists to flush solutions, (4) the concept of "microperfusion" for control of acidosis, (5) the use of solutions containing polyethylene glycol, and (6) the use of a terminal rinse solution. Broadly speaking, the results of these studies have shown that it is possible to improve upon the UW solution by simplification, eliminating several of the components, and that sodium variants, and pharmacological additives, such as chlorpromazine, may yield better results in experimental and clinical trials. It has also been found that there are special requirements for individual organs, rendering the concept of a universal solution unlikely. Of the promising new ideas, microperfusion and polyethylene glycol have been found to be very effective for heart preservation yielding for the first time virtually perfect 24-hour preservation. The concept of a terminal rinse to diminish reperfusion injury has strong experimental support and awaits clinical evaluation. PMID- 1405376 TI - The future of nephrology with special regard to advances in treatment. PMID- 1405377 TI - Race and diabetes as death risk predictors in hemodialysis patients. AB - Case mix and laboratory predictors of death risk were evaluated in 17,185 hemodialysis patients. The laboratory variables most closely associated with the increased death risk borne by diabetic patients (relative to non-diabetics) and White patients (relative to non-Whites) were identified. The analyses of laboratory death risk predictors were similar to those previously reported. Serum albumin concentration is the most powerful death risk predictor among all of the variables, both case mix and laboratory. Statistical models including only case mix variables reveal both race (RRWhites = 1.42) and diabetes (RRdiabetes = 1.43) as significant predictors. Adding creatinine, albumin, and BUN concentrations to the model eliminated diabetes as a significant predictor. Creatinine and albumin accounted for most of the change. Adding only creatinine eliminated race. The data suggest that reduced visceral and somatic protein mass and/or metabolism may be important determinants of mortality in dialysis patients. Because differences in the concentrations of creatinine and albumin explain much of the risk associated with being White or diabetic, differences in nutritional status may explain the reduced survival observed in those groups. Therefore, clinicians should not simply accept without question the notion that diabetics and Whites are doomed to inferior survival. PMID- 1405378 TI - Which comes first, Kt/V or PCR--chicken or egg? AB - We previously hypothesized that PCR is dependent on Kt/V (urea). To test the hypothesis, 30 patients from two hemodialysis (HD) units with PCR values consistently less than 1 regardless of the Kt/V (urea) without an obvious cause (such as malignancy, peptic ulceration, etc.) were identified. These patients were randomized into an experimental group where an increase in the Kt/V (urea) was made or into a control group where a Kt/V (urea) remained unchanged. In the experimental group the minimal increment in Kt/V (urea) was 0.3 plus a minimum requirement of a Kt/V (urea) greater than or equal to 1. The control group were to maintain the existing Kt/V (urea) within +/- 0.2. Urea kinetic modeling was monitored monthly and the patients followed for three months. Of 30 patients, 18 fulfilled the criteria (9 experimental; 9 controls). In the experimental group, the initial Kt/V (urea) was 0.82 +/- 0.19 (means +/- SD); the final Kt/V (urea) was 1.32 +/- 0.21 (P = 0.000). These patients had an initial PCR of 0.81 +/- 0.08. This increased to 1.02 +/- 0.15 (P = 0.005). The control group had an initial Kt/V (urea) of 0.82 +/- 0.16. The final Kt/V (urea) was 0.87 +/- 0.15. Their initial PCR was 0.87 +/- 0.14 and the final PCR was 0.86 +/- 0.087 (P = NS). In the experimental group, the mean increments in Kt/V (urea) and PCR were 0.49 +/- 0.17 and 0.21 +/- 0.16 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405380 TI - Profile of patients on RRT in Europe and death rates due to major causes of death groups. The EDTA Registration Committee. PMID- 1405379 TI - Disturbed calcium metabolism in renal failure--pathogenesis and therapeutic strategies. AB - Absolute or relative deficiency of 1,25(OH)2 vitamin D3 is thought to play a key role in the genesis of secondary (renal) hyperparathyroidism. Elevated concentrations of PTH and--less consistently--diminished concentrations of 1,25(OH)2 vitamin D3 are demonstrable in a considerable proportion of patients with incipient renal failure. Increased PTH concentrations counteract to some extent the trend of 1,25(OH)2 vitamin D3 production to decrease. When iPTH is elevated, prophylactic administration of 1,25(OH)2 vitamin D3 is a logical procedure, even when patients have not yet reached end-stage renal failure. With the use of low doses, the incidence of side effects is low, and excessive lowering of PTH and bone turnover presumably can be avoided. Acute administration of 1,25(OH)2 vitamin D3 to achieve brief episodes of peak plasma levels causes prolonged suppression of pre-pro-PTH mRNA in the parathyroid cell. This provides a rationale to treat symptomatic hyperparathyroidism with intermittent high dose 1,25(OH)2 vitamin D3, either per os or i.v. PMID- 1405381 TI - Effects of calcitriol and non-calcemic vitamin D analogs on secondary hyperparathyroidism. PMID- 1405382 TI - Use of alkaline calcium salts as phosphate binder in uremic patients. AB - In order to prevent aluminum toxicity induced by the association of aluminum phosphate binder with 1 alpha(OH) vitamin D3 derivatives and the use of deferoxamine with its own hazards to diagnose and treat this toxicity, we have shown in 1982 that it was possible to replace the iatrogenic association of aluminum phosphate binder with 1 alpha OH vitamin D derivatives by oral calcium carbonate taken with the meals in order to bind phosphate and correct the negative calcium balance. This led to the disappearance of the crippling aluminic osteomalacia and adynamic bone diseases in our center. The effectiveness of CaCO3 without 1 alpha(OH)D3 derivatives in the control of hyperparathyroidism in dialysis patients has been proven by the appearance in four patients of our dialysis population of an histological idiopathic adynamic bone disease associated with relative hypoparathyroidism, and by the finding that more than 50% of our dialysis population treated by this sole treatment have plasma concentration of intact PTH below twice the upper limit of normal (that is, the threshold above which only significant histological osteitis fibrosa is observed). Besides the compliance problem, the limit of CaCO3 is the occurrence of hypercalcemia which occurs in about 8% of the measurements. Since calcium acetate binds twice as much phosphate for the same dose of elemental calcium as CaCO3, its use has been recommended. However, clinical experience has shown that in spite of the fact that half the dose of calcium element given as acetate does actually control predialysis plasma phosphate as well as CaCO3, the incidence of hypercalcemia is not decreased, probably because calcium availability at the alkaline pH of the intestine is much greater with Ca acetate. When hypercalcemia is frequent (and not explained by autonomized hyperparathyroidism, adynamic bone disease, overtreatment with vitamin D, granulomatosis or neoplasia) it is necessary either to decrease the dose of calcium and complete the necessary binding of phosphate by adding small doses of Mg(OH)2 or Mg carbonate, provided the dialysate Mg is decreased to 0.2 to 0.35 mmol/liter to prevent hypermagnesemia or to decrease the dialysate calcium (DCa) concentration. The decrease of DCa can be made either just when hypercalcemia occurs or on a systemic basis according to the amount of CaCO3 used and to the necessity of associating 1 alpha(OH) vitamin D3 derivatives.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1405383 TI - Risk of adynamic bone disease in dialyzed patients. AB - Renal osteodystrophy presents with a spectrum of histologic abnormalities. A new entity characterized by a marked decrease in bone turnover without osteoid accumulation, that is, adynamic bone disease, has recently emerged. This new form was thought to be primarily related to aluminum accumulation. Since aluminum containing phosphate binders have been widely replaced by calcium salts, adynamic bone disease would be expected to disappear over time. However, not only is adynamic bone disease observed in the absence of aluminum intoxication, its incidence does not seem to have decreased. We conducted a retrospective study in 1,803 patients on chronic maintenance dialysis who were biopsied during the last 10 years and assessed the incidence of adynamic bone disease over time in an effort to elucidate the factors associated with its occurrence. Adynamic bone disease was first seen in 1984 in the laboratory. Its incidence increased gradually over the years and, in 1991, still affected approximately 20% of the patients. The primary factors associated with the occurrence of adynamic bone disease include: (a) aluminum accumulation which is currently found in 60% of the patients on chronic maintenance dialysis undergoing biopsies, (b) increasing age of the patients on dialysis, (c) diabetes, and, possibly, (d) chronic ambulatory peritoneal dialysis. The clinical relevance of adynamic bone disease deserves further study. At present, this entity is associated with a tendency towards hypercalcemia, aging of bone due to stunted bone remodeling, a condition which might be associated with impaired repair of physiologic microdamages, and accumulation of microfractures leading to mechanical incompetence and ultimately to higher risk of fractures. PMID- 1405384 TI - Dialysis related amyloidosis: a disease of chronic retention and inflammation? AB - Dialysis related amyloidosis (DRA) has become a major complication of long-term therapy in chronic hemodialysis or peritoneal dialysis patients. DRA is characterized by the presence of beta 2-microglobulin (beta 2m) in the amyloid fibrils. The pathogenesis of DRA is incompletely understood, but most likely is based on the uremic retention of beta 2m. In contrast, current evidence does not favor a significant role of an enhanced beta 2m synthesis rate in uremic patients. Apart from the beta 2m retention, posttranslational modification of the molecule also seems to be an important step in the amyloidogenesis, since, in addition to intact beta 2m, fragmented beta 2m or beta 2, with altered isoelectric properties can be detected in the DRA fibrils. The occurrence of these beta 2m species could be linked to a chronic intermittent stimulation of monokine release or other subclinical inflammatory processes during renal replacement therapy. Thus, it is possible that, as a consequence of repeated cellular activation, protease release and/or intracellular processing of beta 2m occurs. Renal transplantation has been shown to arrest the further progression of DRA. However, since transplantation is not feasible for a significant number of patients, non-transplant strategies to prevent DRA also need to be evaluated. Some, but not all, retrospective studies on DRA associated symptomatology in patients on chronic hemodialysis with high flux membranes have suggested a lesser prevalence in these patients as compared to patients treated with standard cellulosic membranes. To further clarify this issue and to test whether non transplant therapies indeed may play a role in the prevention of DRA, prospective studies will be needed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405385 TI - Membrane selection and muscle protein catabolism. PMID- 1405386 TI - Polymorphonuclear cell function and infection in dialysis. AB - End-stage renal disease is characterized by enhanced susceptibility for infectious diseases, carrying an important risk of morbidity and mortality. In the host's defense against bacterial infection, a central role is played by phagocytic ingestion of bacteria, followed by their destruction after metabolic production of oxygen free radical species. Our studies have concentrated on the energy delivery by the hexose monophosphate shunt (HMS) to NAD(P)H-oxidase, the enzyme responsible for free radical production. This evaluation was realized by measuring, in whole blood, the CO2 produced from standard quantities of radiolabeled glucose, with data normalized for the number of polymorphs in each sample. Our studies indicate that: (1) glycolysis is disturbed in uremic outpatients from a SCrea of 6 mg/dl and a CCr of 15 ml/min; (2) similar functional disturbances are found in pre-dialysis blood samples of hemodialyzed patients; (3) this functional disturbance is further intensified during dialysis with cuprophan, which is not the case for non-complement activating dialyzers; (4) the response is especially suppressed towards Staphylococcus Aureus, the bacterial species responsible for the majority of infections in uremia; (5) that functional disturbances are mainly related to uremic toxicity, dialyzer membrane bio(in)compatibility, and uremic anemia. Biochemical disturbances in PMNL, induced by a multifactorial patho-physiologic process, may therefore be related to the enhanced incidence of infection in uremic patients. PMID- 1405387 TI - Role of nitric oxide in hemodialysis hypotension. PMID- 1405388 TI - [Foreign body aspiration in childhood]. AB - Damage to the airways and lung parenchyma from aspiration is a common clinical problem with diagnostic and therapeutic challenges. The insult may be acute or chronic. The amount of concentration, chemical composition, and size of particles vary, and the lesion produced may be reversible or irreversible. Death may be immediate or late. Recovery may be complete, or crippling pulmonary disease may follow. In this review is reported on the aspiration of foreign bodies or liquids into the respiratory tract. Specialty: in infancy, esophageal foreign bodies may cause mainly respiratory symptoms. Adequate diagnosis and therapy are discussed. PMID- 1405389 TI - [Complex high altitude climate therapy for children and adolescents with neurodermitis constitutionalis atopica]. AB - Neurodermitis constitutionalis atopica is a multifactor conditioned disease with a very wide range of aetiopathogenetic factors. A standard therapy does not exist. For children and young adults we have come to terms with a treatment concept, that consists in essence of 5 elements. Our basis is the dermatological and allergical treatment plan. We added and integrated factors of high mountain climate, psychotherapy as well as teaching- and children-garden-activities. This complex therapy is condition for optimal results in treating children and young adults. PMID- 1405390 TI - [Kidney involvement in parvovirus B 19 infection in a child]. PMID- 1405391 TI - [Screening for fragile X syndrome in handicapped boys]. AB - From a group of 201 mentally retarded boys 149 were clinically and somatometrically examined. Chromosomal analysis for detection of a fra(X) syndrome was undertaken, when more than 3 of the chosen examination parameters were suspicious or when anamnestic clues for X-chromosomally linked mental retardation were present. 89 boys fulfilled above requirements, 14 of these had a fra(X)-syndrome (15.7%). The following symptoms were found with outstanding frequency: hyperactivity, hypotonic muscles, enlargement of testes, increased length of hands, retarded development of speech, dermatoglyphic abnormalities. If more than 3 of these findings occur, a chromosomal analysis for exclusion of a fra(X)-syndrome should be performed. PMID- 1405392 TI - [Eye diseases and visual disability in extremely low birth weight infants]. AB - 79 consecutively treated very low birth weight newborns (less than 1000 g) were systematically examined in the postpartal period and after a follow-up of 2 to 5.5 years. Retinopathy of prematurity was found in 19 eyes of 10 children (maximum stage III-IV). At a minimum age of 2 and maximum age of 6 years, when 42 of these children could be reexamined, including all children with earlier retinopathy of prematurity, 10 children suffered from minimal to moderate retinal pathology due to inactive retinopathy of prematurity (4 eyes with dragging of vessels and macula), but 9 children exhibited a minor visual disability due to strabism, higher ametropia, anisometropia, and amblyopia. This stresses the need for opthalmological follow-up in low birth weight babies with 6 months and 3-4 years of age. PMID- 1405393 TI - [Biometric data of eyes after the onset of acute glaucoma]. AB - Biometric measurements were performed in 67 patients after acute glaucoma and in 67 patients of a matched control group. For patients with acute glaucoma the subjective refraction was +0.91 +/- 2.82 dpt, ocular axial length was 21.73 +/- 0.96 mm, lens thickness was 4.95 +/- 0.63 mm and the ratio lens thickness to ocular axial length amounted to 2.27 +/- 0.29. There was a statistically significant difference between the glaucoma and the control group concerning the parameters subjective refraction, ocular axial length, lens thickness and the lens thickness to axial length ratio. A statistically significant positive correlation was found between corneal radius and axial length, both, in the control and the glaucoma group, a significant negative correlation between axial length and subjective refraction only in the control group. In contrast to other authors, who reported on patients with narrow angle glaucoma with and without acute attack; we found no significant difference. These results support the suggestion that biometric data do not allow a prediction whether a patient with narrow anterior chamber angle will suffer glaucoma attack or not. The etiology of this disease seems to have a multifactorial origin. PMID- 1405394 TI - [Perforating keratoplasty in endogenous eczema. An indication for systemic cyclosporin A--a retrospective study of 18 patients]. AB - Endogenous eczema represents a considerable risk for perforating keratoplasty because of the associated chronic surface disorders and complex immunological disturbances. Between December 1986 through October 1991 we performed 24 perforating keratoplasties in 20 eyes of 18 patients with endogenous eczema suffering from keratokonus, atopic keratokonjunctivitis and bullous keratopathy after intracapsular cataract extraction. During the follow-up period of 16 (3-48) months 6 transplants failed mostly due to surface problems as well as immune reactions and bacterial transplant infections. Systemically administered ciclosporin A was found to eliminate many of the previously unsolved problems. In summary, 18 out of 20 eyes achieved an improved visual acuity with clear transplants. PMID- 1405395 TI - [Eye changes in acanthosis nigricans maligna--possible effect of growth factors in the etiopathogenesis of this paraneoplastic disease picture]. AB - A 64-year-old white male presented to our hospital with hyperplastic tarsal and to a lesser degree bulbar conjunctivae. Approximately one month later the full clinical picture of acanthosis nigricans maligna developed. In addition to ectropia of the lower eyelids he showed madarosis; neither the linea grisea nor the lacrimal points were discerneable. On gastroscopy a diffusely growing gastric adenocarcinoma adjacent to the cardia was found and later confirmed histopathologically. The computertomography of the abdomen demonstrated one solitary metastasis to one parapancreatic lymphnode. It is generally assumed that in the course of paraneoplastic syndroms products secreted by the tumor induce changes in the target organs, e.g. the conjunctiva and the skin. In the presented case (1) southern blot analysis of the tumor tissue proved an increase of Epidermal Growth Factor-receptors, (2) immunohistochemistry showed prominent staining for Transforming Growth Factor-alpha. In conclusion, this case is suggestive of a possible link between growth factors and acanthosis nigricans maligna. PMID- 1405396 TI - [Canthaxanthin retinopathy. Follow-up of over 6 years]. AB - After long-term treatment with high dosages, canthaxanthin causes a characteristic retinopathy with circular, macula surrounding crystals. As changes in retinal functionning disappear relatively easily after withdrawal of the drug, the crystals dissolve rather slowly--over about several years. Five patients showing a profound crystalline retinopathy were re-examined with an average of 69.7 months after withdrawal of the canthaxanthin-containing drug. Three of the patients were treated for erythropoetic protoporphyria (EPP) with Phenoro (2/5 beta-carotene, 3/5 canthaxanthin), two sisters took a canthaxanthin-containing formulation (1/8 beta-carotene, 7/8 canthaxanthin) for cosmetic reasons. Two female patients complained about an increased glare sensitivity, which was explainable for one of them with a subcapsular cataract. The retinal crystals decreased quite differently. Minor deffects of the retinal pigment epithelium remained unchanged in two patients. They increased slightly in the female patient with the smallest crystal formation but highest plasma cholesterol. Shortly after withdrawal of the drugs usually an increase of a-wave amplituded of the electroretinograms was found. The a-waves returned to normal and the b-wave amplitudes showed an increase up to the final control paralleling the reduction of the retinal crystals. A- and b-wave peak latencies which were prolonged under treatment returned to normal. PMID- 1405397 TI - [Surgery of Tenon's capsule in squint operations]. AB - There is a good chance to reduce the scaring between conjunctiva, Tenon's capsule, muscle and sclera after surgical treatment of rectus and oblique muscles if a careful reconstruction of Tenon's capsule is made. In the rare cases that you have to reoperate, you will experience the benefit of these additional stitches (7-0 vicryl) that restore the integrity of Tenon. PMID- 1405398 TI - ["Erroneous orthograde" direction of flow in the supratrochlear artery as a cause of Doppler ultrasound diagnostic error in severe (filiform; 90%) stenosis of the carotid bifurcation]. AB - Author reports on mistake in Ultrasound-Doppler-Sonography by an neurologist. A 82-year-old women with leftside Amaurosis fugax was referred by her family doctor, internist. Neurological examination, above all Doppler-Sonography, results in "normal findings". Examination by author however detected filiforme stenosis of left internal carotid artery in spite of "orthograde" direction of blood-flow in final branches of ophthalmic artery. This perhaps was the cause of neurological misdiagnosis. PMID- 1405399 TI - [Choroid ganglioneuroma in childhood]. AB - The authors report on a case of a 4 1/2-year-old male child, who was referred because of a convergent microstrabisms of the right eye combined with amblyopia and minimal anisometropia and progressive decrease of the visual function from 0.6 to 0.05 although occlussion-therapy was performed. Funduscopy showed a melanoma-like choroidal tumor temporal-inferior of the macula with shallow retinal detachment and severe cellular vitreal infiltration. Because of the progression the tumor was resected by the transscleral technique of Foulds (1983). Histology showed a ganglioneuroma of the choroid, which has not been reported in this localisation up to now. Usually it is found in the retroperitoneal area and in the mediastinum, specially in case of neurofibromatosis (Recklinghausen). This disease could not be objectified in this meanwhile 7-year-old boy. At the last control visual acuity was 1/20, ophthalmoscopy showed gross streaky depigmentation in the macular region, the retina was attached. PMID- 1405400 TI - [Retinal lymphoma--simulating uveitis]. AB - A rare form of malignant large-cell non-Hodgkin's lymphoma or reticulum cell sarcoma is confined to the eye and central nervous system (CNS). We report the case of a 62-year-old man, who presented with recalcitrant progressive uveitis in his right eye. Although lymphoma was suspected, the patient refused to undergo vitrectomy. Over one year he developed large blister-like solid scattered lesions of the retinal pigment epithelium (RPE) in the same eye. Repetitive neuroimaging detected no CNS involvement. After developing optic disc-swelling and discrete RPE-changes in the left eye also, the patient agreed to enucleation of his right eye. Histopathology and Immuno-histochemistry revealed malignant intraocular large cell-lymphoma invading all eye-tissues. Liquor cytology showed lymphomatous cells. Suffering from high grade malignant lymphoma with CNS ivolvement, the patient had to undergo radiation therapy of the orbits and neuroaxsis as well as intravenous and intrathecal chemotherapy. Papilledema of the left eye resolved quickly and completely, RPE-infiltrations disappeared and led to discrete punched out lesions with no scarring, the lens remained transparent over the whole observation period of 25 months. the patient has been surviving for more than 52 months after first suspicion of malignant lymphoma, he has retained full vision in his left eye until now. PMID- 1405401 TI - [Quantifying suture tension of corneal sutures with the suture forceps with strain gauge strips]. AB - To achieve uniform tensions on corneal stiches a modified tying forceps was developed. This forceps provides the possibility to measure the tension which is put to a nylon thread (10-0) by means of surface mounted strain gauges detecting the forceps jaws' bending. The results are registered and displayed electronically. To obtain a preselected tension, a limit value switch and a tare unit is used. A first series of registrations showed reproduceable values and confirmed a linear correlation between forceps jaw bending and traction force. A prototype and possibilities of technical improvement are demonstrated. PMID- 1405402 TI - [PC software for evaluating the Farnsworth-Munsell 100-Hue test]. AB - This computer program is designed for faster elaboration of the Farnsworth Munsell 100-Hue test. It is thus made user friendly, in that faultless input of data can be achieved, even by an untrained person. Evaluation is facilitated by the opportunity of representing two results at the same time. Examples of typical colour vision deficiencies are stored in a file and can then also be called up. Storing the results in a special data file helps to avoid the time consuming printing process. However, a hardcopy is supported by storing the last grafic in a standard PostScript-file, thus giving easy access to any printer. This program is applicable for IBM- or compatible PCs. Extensive use is possible by means of a software interface with the wide spread database-system DBASE. PMID- 1405403 TI - [125 years ophthalmopathology in Tubingen. Change in the times and spectrum of findings]. AB - The beginning of ophthalmopathological activities at the University Eye Clinic Tubingen, Germany, can be dated back to the year 1868, as at this time the continuous counting of investigated, ophthalmological specimens was started. So the ophthalmopathological department in Tubingen will be 125 years old in 1993. In a review its history is described with particular regard to the first period and the change in the kind and frequence of diagnoses. PMID- 1405404 TI - [The most frequent causes of loss or impairment of vision in children and adolescents]. AB - On the basis of examination of 100 persons aged 3-18 years registered in the Olsztyn Division of the Union of the Blind the authors determined the causes which led to the loss of vision or of its impairment. The most frequent cause of the invalidism of the visual system were: errors of refraction (32%), optic atrophy (24%), congenital cataract (16%), retinal and choroidal degeneration (9%), retrolental fibroplasia (6%), anophthalmia or malformation of the globe (4%), coloboma of the iris or choroid (3%), retinoblastoma (3%), injuries (2%) and congenital glaucoma (1%). PMID- 1405405 TI - [Eye burns in children and adolescents]. AB - The authors present a material of 91 eyes in 66 children aged 2 days to 16 years, who sustained burns of the eyes. Fifty one eyes (1st group) was burned by thermal or chemical means, mainly by lime; 40 eyes (2d group) sustained chemico mechanical injuries caused by explosions of petards or miner's detonators. Bilaterality of the injuries was seen in 50 p.c. of cases of the 1st group and in 25 p.c. of cases of the second group. Reduction of the visual acuity down to light perception was observed in 19.7 p.c. of cases of the 1st group and in 22.5 p.c. of cases in the 2d one; at the same time 2 cases of this group became blind. The cause of deterioration of the visual acuity in the group of chemico-thermal trauma were the corneal opacities, in the group of mixed injuries--changes in the posterior segment of the eye. PMID- 1405406 TI - [Late results of the treatment of eye burns]. AB - An analysis of patients treated in the Ophthalmic Department in Bydgoszcz for eye burns in the 10 years period from 1980 till 1990. Taken into account were the causes of burns, the treatment installed in the early period and in cases of late complications. All the patients were asked to call in for a control examination in order to compare the condition of the eyes at the date of discharge and in the long-lasting time. Among 118 eyes in 91 the visual acuity amounted 0.5-1.0, in the remaining 25 it was only hand movements--0.4. The main causes of low visual acuity were: corneal leucoma, secondary glaucoma, complicated cataract. The eye was enucleated in 2 patients because a painful ocular atrophy developed in the course of the pathological process. These were the cases of thermal burns combined with a mechanical injury. The obtained results were evaluated as sufficiently favourable and comparable to the data of other authors. PMID- 1405407 TI - [Prevention of amblyopia by active production of the macular fixation reflex in infants]. AB - Among 1455 examined babies aged 3 months the authors found a lack of normal fixation reflex in both eyes in 155 and in 52 in one eye only. In these eyes the parents applied 3 times a day an alternate occlusion of eyes or of the master eye only showing the babies interesting toys. After 2 weeks 83 babies showed normalization of fixation and after following 2 weeks of over described occlusion only 8 of them did not reveal a normal fixation reflex. These babies exhibited also a convergent squint. The pleoptic treatment by means of an euthyscope was installed, followed by normalization of the fixation reflex in 3. The rest of the patients was treated with spheroprismatic glasses by localization method. PMID- 1405408 TI - [Cryotherapy of corneal burns]. AB - Presented are the results of treatment of 59 patients with severe chemical and thermal burns of the cornea who--besides being subjected to a traditional procedure--were also treated by cryotherapy. In the majority of cases low temperature considerably hastened the process of the regeneration of corneal epithelium and the clearing up of its opacification. It considerably influenced the shortening of the treatment period and the improvement of the visual acuity. PMID- 1405409 TI - [Subconjunctival autohemotherapy of eye burns in our cases]. AB - The authors present the results of subconjunctival autohemotherapy of thermal and chemical burns in 940 eyes which concerned 734 patients; simultaneously they discuss the causes of these burns. The obtained results confirm the very well known opinion that subconjunctival autohemotherapy applied together with the vasodilating drugs is still a very valuable method in the treatment of ocular burns. PMID- 1405411 TI - [Experimental studies of the effect of carbon monoxide on the retina of guinea pigs of different age]. AB - Young and adult guinea pigs had been put in a chamber containing an 4-5 per cent addition of CO in the air. After 7 days of intoxication the authors performed a histopathological and histochemical examination of the retina. They discovered disturbances of the histological structure of the retina, a decrease of the content of nucleic acids and alkaline phosphatase and an increase of the acid phosphatase. The more pronounced intensification of the pathological changes was seen in the retina of younger individuals. PMID- 1405410 TI - [Results of the treatment of post-traumatic exogenous siderosis of the eye]. AB - In the period of 3 years the authors observed 7 patients with an intraocular foreign body not diagnosed or to late treated. The signs of siderosis appeared very early (after some days) or did not appear even after 1-2 years. The absolute removal of the foreign body together with topical, intraconjunctival application of desferal and its general, intramuscular injections condition the withdrawal of siderosis and the preservation of vision, although the electroretinographical curve remains forever pathological. A scrupulous kinetic and static visual field examination may help in diagnosis of the ocular siderosis in cases of lack of electrophysiological instrumentarium. PMID- 1405412 TI - [Effect of drugs inhibiting the formation of hydroxide radicals on healing of experimental corneal ulcer]. AB - The 60 per cent water solution of dimethyl sulfoxide (DMSO) was used in the investigations. It was instilled into the conjunctival sac of an eye with experimental corneal ulceration. The dimethyl sulfoxide is inhibiting the formation of hydroxide radicals which cause a damage of the tissue in the course of inflammation. Clinical observations as well as histochemical and histopathological examinations showed that ulcerations treated by dimethyl sulfoxide healed faster than those from the control group and reactions to acid mucopolysaccharides++ returned more rapidly to normal values. PMID- 1405413 TI - [Measurement of lens transparency in workers at risk of developing of glassblower's cataract]. AB - The authors evaluated the transparency of lenses in persons on a stand predisposing to the formation of a glassblower cataract as well as in office clerks. They used for their measurements a fluorophotometer (Fluorotron Master) and an opacity lensmeter. In a group of 40 ironmasters they found a considerable fall in light transparency through the lens and a significant increase of the lens autofluorescence in comparison with a group of office clerks. The quantitative measurement of lens transparency by means of a fluorotron and a opacity lensmeter creates the possibility of an earlier detection of a ++pre cataract condition. PMID- 1405414 TI - [Condition of the corneal endothelium after penetrating injuries]. AB - The examination of the corneal endothelium with a posttraumatic scar was performed by means of a corneal microscope with an endothelial cell counter in patients with traumatic cataract before its removal with simultaneous implantation of an artificial intraocular lens. It was established that the density of the endothelial cells in these eyes before surgery amounted 950 3000/mm2. The density of the cells below this value creates a danger of formation of bullous keratopathy after the surgical intervention. PMID- 1405415 TI - [Study od visual evoked potentials in employees of the Chemical Works in Bydgoszcz]. AB - Examined was a group of 50 persons aged 25-60 years employed in the Chemical Works in Bydgoszcz. The time of professional contact counted from 4 month to 31 years. During this time the workers had contact with the following--at least 2- compounds: chlorine and its derivates, benzene, propylene, katolite, phosgene, isocyanianes, epichlorohydrine and others. In 33 among 50 examinees (66 p.c.) the authors detected a normal record of VEP. A pathological record was observed in 17 persons (34 p.c.). The greatest per cent of pathological records concerned a group of professional practice amounting 20-29 years as well as persons undertaking the work before the 25th year of life. The most frequent pathological record of VEP was a curve with reduced amplitude of the P wave; the least frequently seen was the debasement of the amplitude together with the elongation of the latent time of this wave. PMID- 1405416 TI - [Analysis of the place of regulation of C-11 transmitters at the Tele-electronic Works "Telkom-Telfa" in Bydgoszcz from the point of view of visual hygiene]. AB - The authors performed a detailed analysis of 100 positions of regulation of the C 11 transmitters in the "Telcom-Telfa" ++Tele-electronic Works in Bydgoszcz. It was determined that the requirements for the condition of the eyes and the lighting at this workstand are considerable. Conclusions and recommendations tending to improvement of the working conditions are drawn up. Proposed is eventual rationale leading to the reduction of the eyestrain and facilitation of the work. PMID- 1405417 TI - [The incidental heart sound. Study of clinical diagnostic certainty and possible causes]. AB - The diagnosis "innocent murmur" is made when there is no evidence for a heart disease either by history nor by examination, auscultation, electrocardiogram or echocardiography. The purpose of the present study was to determine the usefulness of echocardiography for diagnosing of an innocent heart murmur and further to compare the findings of ultrasound with those of the clinical examination. Children were accepted for the study after clinical examination and evaluation of the electrocardiogram (but before echocardiography) only when two independent pediatricians did not realize any symptoms of a heart disease. A total number of 200 children were examined; 121 were male and 79 female. 194 children (97%) had an innocent murmur, six children (3%) a heart disease [atrial septum defect (3), bicuspid aortic valve (1), aortic stenosis (1) or pulmonary stenosis]. The sensitivity and positive predictive value of clinical examination and auscultation ranged from 92% to 99%, the specificity from 50% to 60%. In six cases the initial diagnosis had to be changed after echocardiography. Three times an innocent murmur was diagnosed as a heart disease and another three times a pathological murmur was regarded as innocent. Left ventricular bands were seen in 53 (26,5%) children and they significantly correlated with the musical heart murmur (77%). If there was no false tendon, the murmur was mostly an uncharacteristic one (74% (less than 0,001). The echocardiographic findings were not different of those children without a murmur or heart disease. The average peak velocity in the ascending aorta was 143,1 +/- 23,6 cm/s (87-215 cm/s), the shortening fraction 36,2 +/- 6,3%. We could not find a correlation between velocity, shortening fraction and aortic diameter. PMID- 1405418 TI - [Bland-White-Garland syndrome. Clinical aspects, diagnosis, therapy]. AB - The anomalous origin of the left coronary artery from the pulmonary artery (Bland White-Garland Syndrome) is a rare congenital malformation reported to occur in 0.25-0.5% of all congenital cardiac anomalies. The clinical and pathomorphological picture can be classified into 2 types: infantile or adult. The infantile type is thought to lack coronary collaterals; this explains the bad prognosis and symptoms of non-operated patients. In the adult type collaterals are present or have developed in time to provide adequate blood supply to the myocardium. No history of cardiac complains and a nearly normal ECG are common findings. Echocardiography and cardiac catheterisation are mandatory diagnostic tools. The value of new methods like NMR, "stop-flow" angiography and color doppler flow mapping is still in discussion. The reimplantation of the coronary artery and Takeuchi-Operation are well established surgical methods. The time for the operation and prognostic outcome are related to the preoperative underlying myocardial damage measured by left ventricular function. PMID- 1405419 TI - [Alcohol in pregnancy and fetal heart damage]. AB - Alcohol abuse and addiction during pregnancy can induce damage of the heart muscle and heart defects in the offspring. Between 1973 and 1991 216 children with fetal alcohol syndrome were diagnosed and examined for congenital heart defects. In 63 children (= 29,1%) heart defects were present, established mainly by heart catheterization and/or echocardiography. Most frequently ventricular septal defects (24/63) and atrial septal defects (23/63) occurred, less frequent were AV-defects (3), PDA (3), Fallots teralogy (5), and other malformations (5). Biopsy during heart surgery in 3 children revealed histological and electron microscopic changes of alcohol-cardiomyopathy. Heart defects are predominantly found in children with higher degree of severity concerning the clinical syndrome, less frequently in alcohol effects (4/38 = 11%). Alcohol in pregnancy, even in the course of so called social drinking, usual drinking and binge drinking has to be considered as an essential and preventable co-factor within the multifactorial etiology of congenital heart defects. PMID- 1405420 TI - [Progress and change in nuclear magnetic resonance diagnosis of congenital and acquired heart defects]. AB - Since 1987, the authors have examined 186 patients (76 girls, 110 boys) with a variety of congenital and acquired heart diseases by means of magnetic resonance imaging (MRI). The patients' ages ranged from 2 days to 20 years (mean age 3.97 years). During the study new techniques were developed, which extend the applicability of MRI. Especially two-dimensional and three-dimensional angiography are demonstrated and discussed. Using all diagnostic tools offered by MRI more than 90% of cardiovascular malformations are correctly diagnosed. MRI is of unquestionable value in the evaluation of the thoracic and abdominal aorta and in demonstrating the vascular status in pulmonary atresia and anomalous pulmonary venous return. It may be useful if question arise in patients with complex lesions, intra- and extracardiac tumours and cardiomyopathies. Although MRI is still under investigation, it may play a major role in diagnosing congenital heart diseases. PMID- 1405421 TI - [PCB exposure of children in East and West Germany]. AB - In order to assess the exposure to polychlorinated biphenyls (PCB) in children from East- and West-Germany 276 fat tissue samples were analysed. Total PCB concentrations were calculated by means of six PCB congeners: No. 28, 52, 101, 138, 153 and 180. In children from East-Germany the mean total PCB levels amounted to 0.899 mg/kg (median 0.674) and were significantly higher than in children from West-Germany (0.766/0.555 mg/kg; p less than 0.05). Regional differences were only seen within East-Germany. In fat tissue of children with high intake of breast milk (lactation period greater than 12 weeks) PCB levels were significantly elevated compared to those with low intake of mother's milk (lactation period less than 12 weeks). A further reduction of PCB in our environment is necessary so that breast milk can be recommended for sucklings without any restrictions. PMID- 1405422 TI - [Measuring skin temperature in premature infants. Comparison of infrared telethermography and electric contact thermometry]. AB - In a group of 6 premature infants, mean weight 1776 g, we measured skin surface temperatures, comparing infrared telethermography (San-ei Thermo-Tracer 6T62) and conventional skin thermometry (Eidatherm). Surface temperatures were measured at 10 different sites, with the infants nursed in an incubator. The same methods were used to compare temperatures on the lower arm of an adult. The results of the two different techniques showed only minor differences of approximately 0,2 degrees C. These discrepancies could be explained by problems of either method. They could also be attributed to the fact, that the emissivity of human skin is not exactly identical with the emissivity of a perfect black body. In clinical practice, infrared thermography and conductive thermometry can be used for determinations of body surface temperature of premature infants, also under the condition of high temperatures and high humidity within an incubator. PMID- 1405423 TI - [Laser Doppler flowmetry in newborn infants with low birth weight. The effect of differences in humidity on peripheral circulation]. AB - In a group of 10 low birth weight infants we measured skin temperature using infrared thermography and laser Doppler flow in central and peripheral regions of the body. After elevation of incubator humidity from 40 to 80% skin temperature of the foot rose significantly (p less than 0.01). At the same time there was a significant increase (p less than 0.05) of laser Doppler flow. Temperature and laser Doppler flow in the area of the abdomen did not show significant changes. Low birth weight infants are able to regulate peripheral blood flow after changes of ambient humidity. With the method of laser Doppler flowmetry thermoregulatory responses in the microvascular bed can be measured in these infants. PMID- 1405424 TI - [Neurosonographic findings in premature infants and infants with intrauterine growth retardation with a birth weight below 1,500 grams]. AB - The cranial ultrasound of 111 preterm infants were reviewed. 57 patients were appropriate for gestational age (AGA) and 54 small for gestational age (SGA). In the two groups, the incidence of peri-intraventricular hemorrhage (PIVH), posthemorrhagic ventricular dilation (VM) and peri-ventricular leucomalacia (PVL) was compared. PIVH was more common in AGA than in SGA babies (36.8% vs 18.5%). In both groups (AGA and SGA), birth weight less than 1000 g should be considered a further risk factor for hemorrhagic brain lesion (72.2% in AGA babies less than 1000 g and 20.5% ind AGA babies greater than 1000 g birth weight, p less than 0.01) (34.8% in SGA babies less than 1000 g and 6.4% in SGA babies greater than 1000 g birth weight, p less than 0.05). However, ischemic brain lesions (PVL) were not dependent from birth weight (p greater than 0.5). This study shows that low birth weight infants are an eterogeneous group of babies with different risk of hemorrhagic or ischemic cerebral lesion depending on gestational age and birth weight. PMID- 1405425 TI - [Respiratory death space and ventilation of newborn infants]. AB - The effect of dead space reduction was studied in 10 VLBW infants (GA 26-31 wks, mean BW 1100 grms) on mechanical ventilation using a constant flow ventilator with a flow sensor device (Draeger Babylog 8000, Lubeck, Germany). Shortening of the endotracheal tube and removal of the flow sensor resulted in a calculated 50% reduction of dead space (-2.3 ml) and in a fall of tcpCO2 from (mean and range) 45 (40-49) to 35 (31-36) mmHG. This corresponds to a increase of alveolar ventilation of 22% as predicted by calculation of the dead space changes. Further attempts were made in reducing dead space ventilation by using endotracheal tubes conceived for jet ventilation, using the jet entry for the inspiratory side, or by introducing a separate continuous inspiratory flow to the tip of the endotracheal tube. Besides a routinely performed shortening of the ET tube this means of ventilation was used with success in two VLBW infants with desperate respiratory situations who both survived, in an older infant with high-grade tracheal stenosis to wean him from the respirator and in three neonates with congenital diaphragmatic hernia in conjunction with delayed operative repair who could be weaned from respiratory support 4, 13 and 20 days post surgery. We conclude that dead space reduction is a means to achieve gentle ventilation and to reduce lung damage from artificial ventilation. PMID- 1405426 TI - [Is outdoor running exercise suitable for detecting bronchial hyperreactivity in children with mild episodic bronchial asthma?]. AB - Bronchial hyperreactivity (BHR) can be proved by various methods. 21 children, 14 asthmatics and 7 healthy subjects were submitted to inhalative methacholine challenge as well as to 'free running' as a form of exercise challenge in a randomized sequence. For the methacholine inhalation a standardized procedure was followed and the provocative concentration defined (PC20) at which a decrease of more than 20% in FEV1 was found. There is no real standardisation for 'free running' (concerning temperature and humidity of the inspired air; individual level of exercise) but subjects had to run for 6 minutes while the heart rate should have been between 170 and 180 beats/minute. This increase in pulse rate relates to a submaximal work at which 60-85% of maximal O2 uptake are obtained. A decrease of 15% from basic value of FEV1 was defined as a positive result. By the use of methacholine inhalations we found 16 children (14 diseased, 2 controls) to be hyperreactive, whereas only 3 of them showed a positive result after 'free running'. We conclude, that firstly, methacholine provocations and exercise challenges assess different kinds of bronchial reactivity, secondly, 'free running' as a form of exercise is very difficult to standardize and therefore prone to errors and thirdly, 'free running' is not sensitive enough to assess BHR in children with mild asthma bronchiale if used as the only form of challenge. Problems concerning measurement of BHR are discussed. PMID- 1405427 TI - [The anion gap--screening for hyperlactatemia in critically ill children?]. AB - Serum lactate provides important information about tissue perfusion in critically ill patients. Aim of this study is to evaluate anion gap as a screening method to detect hyperlactatemia at a pediatric intensive care unit. In infants and children of different ages and diagnosis we determined blood gases, electrolytes and lactate. Sensitivity of anion gap was increasing with increasing hyperlactatemia. For the total population the test exhibited a sensitivity of 64% and a specificity of 76%, respectively. The power of anion gap as a screening method to detect hyperlactatemia was similarly fair for all age groups. Therefore hyperlactatemia has also to be included in the differential diagnosis of non anion gap metabolic acidosis. PMID- 1405428 TI - [Prenatal diagnosis of primary megaureter]. AB - 22 of 114 infants with prenatal diagnosis of urinary tract malformations (15 boys) had obstruction of the ureterovesical junction caused by primary megaureter (n = 14), ureterocele (n = 7), or ectopic ureter (n = 1). Infants with infravesical obstruction or refluxing systems were excluded. All infants had a normal renal function and probably only 5 of them (23%) would have been diagnosed during infancy without prenatal diagnosis. A total number of 26 renal units was evaluated. Six infants had ipsilateral duplication with additional contralateral duplication (n = 2) or vesicoureteric reflux (n = 2). A nonfunctioning kidney or upper pole of duplication was noted in 7 units (5 with ureteroceles); in two instances a moderately dysplastic kidney was present. One boy with urinary infections developed renal scarring during follow-up. Conservative treatment was performed in 14 renal units while 12 units of 11 children had 22 operations (9 temporary diversions) at a mean age of 4,6 months. A severe operative complication was noted in one infant. Conservative treatment is justified in many infants with primary obstructive megaureters but severe renal dysplasia may be present even neonatally. Yet we feel that prenatal diagnosis benefitted most infants, especially those with the most severe malformations. PMID- 1405429 TI - [Recommendations of the German Society of Pediatric Infectology for antibiotic therapy of group A streptococcal tonsillopharyngitis]. PMID- 1405430 TI - Large amounts of 1 beta-hydroxylated bile acids in urine during taurine therapy. AB - The management of infants with cholestasis remains a difficult challenge. On the hypothesis that taurine is effective in treating neonatal cholestasis, taurine (1 g/day, per os) was administered to 2 patients with neonatal hepatitis and the bile acids were analyzed using gas chromatography-mass spectrometry (GC-MS). The serum levels of bilirubin and bile acids were significantly decreased by taurine. Before the treatment, cholic acid (CA) and chenodeoxycholic acid (CDCA) were predominant (79.2% in both patients) in the urine. There was a significant elevation of 1 beta-hydroxylated bile acids (1 beta BA), especially 1 beta, 3 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid (CA-1 beta-ol), in urine collected during the taurine therapy, and 1 beta BA became predominant (57.7-78.3%). Therefore, increased amounts of urine 1 beta BA were excreted during taurine administration. Taurine therapy is recommended, because it might be effective for treating neonatal cholestasis. PMID- 1405431 TI - A study on polyethylene glycol electrolyte lavage solution and sodium picosulfate combined pretreatment method for colonoscopy. PMID- 1405432 TI - The cystic growth of a subependymal giant-cell astrocytoma with tuberous sclerosis. AB - A case of a 7 year-old boy with subependymal giant-cell astrocytoma is reported. CT scanning of this patient for 6 years showed the cystic growth of the astrocytoma. The surgical indication and importance of periodic CT studies for subependymal giant-cell astrocytomas associated with tuberous sclerosis are discussed. PMID- 1405433 TI - Pattern recognition of continuity of discrete data points by scale changed plots. AB - Graphs composed of a large number of data points plotted on an appropriate scale enables us to pattern recognize a specific continuous curve. This principle was used to follow signals from proton nuclear magnetic resonance as a function of pH in a large biomolecule, staphylococcal nuclease. The analysis was automated by auto peak-picking routines and by transferring the results to a graphic program, Graphic Operating System (Roome & Peterson, 1985). Expansion and contraction of the scale made it possible to differentiate specific tyrosine and histidine titration curves. This type of analysis is applicable for assignment of specific curves from a large number of data points which change as a function of perturbations. PMID- 1405434 TI - Immunological study of the association between hepatocyte damage and HBc antigen. AB - To identify the target antigen during hepatocyte damage in hepatitis type B virus (HBV) infections, the expression of HBc and HBs antigens, and beta 2 microglobulin (BMG) were studied in liver tissue. Serial changes of serum DNA polymerase (DNA-P) activity and HBV DNA were also measured. After the onset of acute hepatitis, HBs antigen in liver tissues was observed from many patients; but HBc antigen was rarely detected. In liver tissues of patients with chronic hepatitis, HBs antigen was consistently positive, irrespective of the changes in sGPT. On the other hand, HBc antigen was frequently positive both preceding and during the culmination period for sGPT. The distribution of HBc antigen in the hepatocyte was mostly cytoplasmic. During the same period the serum DNA-P and HBV DNA were frequently positive. Immunoelectron microscopy showed that reaction products with HBc antigen existed in the cytoplasm and the cell membrane. These results indicate that HBc antigens become the target, when HBV infected hepatocytes are eliminated. PMID- 1405435 TI - Invisible cardia cancer metastasis to the diaphragm. AB - The best surgical procedure to treat a carcinoma in the gastric cardia remains a controversy because the carcinoma is often advanced and there are other unknown factors. In this article the incidence of invisible metastasis from cardia cancer to the diaphragm will be analyzed using an experimental cardia cancer model and clinical studies. An experimental cardia cancer was induced by an endoscopic injection of VX2 cancer cells into the submucosal layer of the esophago-gastric junction in rabbits using a 27G needle and an Olympus BF-4B2 bronchofiberscope. A total of 26 cardia cancer models for Borrmann type 2 or 3 were produced. Of these, six (23%) had visible cancer metastases in the diaphragm, including 4 cases with direct invasion and 2 cases with peritoneal dissemination on the surface of the diaphragm. Four (20%) of the remaining 20 were histologically found to have macroscopically-invisible cancer metastases mainly in the lymph vessels of the left hemidiaphragm. From 1985 to 1988, 22 clinical cases of cardia cancer were managed by a combined total gastrectomy with a partial diaphragm resection through a left thoracoabdominal approach. When widely resected, reconstruction was performed using a latissimus dorsi muscle flap. Six (27%) of these 22 were also histologically found to have macroscopically-invisible cancer metastases to the diaphragm, including 1 (11%) of the 9 well-differentiated type and 5 (39%) of 13 poorly-differentiated type adenocarcinomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405436 TI - Retrospective studies of gastric subserosal (ss) cancer--in comparison to pm- and se-cancers. AB - The deepest gastric cancer invasion into the tela subserosa is expressed as the ss-cancer. Subserosal gastric cancers (ss) can be divided into 4 subtypes; ss alpha, ss beta, (ss gamma) and ss gamma, pathologically. These four subtypes were compared to cancerous invasion into the muscularis propria (pm-cancer) and cancerous invasion with serosal exposure (se-cancer). During the 10 years from 1979 to 1988, a total of 938 cases with gastric cancer were resected in the First Department of Surgery, Kurume University Hospital. Of these, 104 (11.1%) cases were ss-cancers, consisting of 28 (27%) cases of ss alpha, 33 (32%) cases of ss beta, 4 (3%) cases of (ss gamma) and 39 (38%) cases of ss gamma. Pm-cancers and ss-cancers were most frequently observed in Borrmann type 2, macroscopically, and in the differentiated type, histologically. On the other hand, se-cancers were frequently observed in Borrmann type 3 and in an undifferentiated type. Positive lymph node metastases were found in 49.1% of pm-cancers, in 50.0% of ss-cancers and in 79.9% of se-cancers (p < 0.01), with no statistical difference in the positive lymph node metastasis rates for the subdivisions of ss-cancer. In ss cancer, however, there was a statistical difference in prognosis according to the tumor size, and according to the degree of subserosal infiltration. The 5-year survival rate was 82.3% for pm-cancer, 75.0% for ss-cancer and 34.7% for se cancer (p < 0.01). PMID- 1405437 TI - Gastric cancer surgery in the elderly. AB - Although there is a decreasing number of gastric cancer patients in Japan, the number of patients over 80 years of age is increasing. Forty patients over 80 years of age (from 80 to 88 years) with gastric cancer (Group 1) during the 10 years from 1980 to 1989 were retrospectively investigated and compared with those 70-79 years of age (Group 2). The resectability rate was 80% in Group 1 and 89% in Group 2. Early gastric cancer was observed at a rate of only 25% in Group 1 and 39% in Group 2. Pathologically, the differentiated type occurred in 78% of those in Group 1 and 68% of Group 2. Total gastrectomy was performed in only 6% of the resected cases in Group 1 and in 25% of Group 2. A combined resection including such operations as pancreatico-splenectomy or splenectomy (PS) was employed in none of the total gastrectomy cases in Group 1 and in 30% of Group 2. R3 gastrectomy was performed in none of the patients in Group 1 and in 21% of those in Group 2. Postoperative complications occurred in 25% of Group 1 patients and in 12% of Group 2 patients. Anastomotic leakage occurred in 3% of those in Group 1 and in 4% of those in Group 2. The 5-year survival rate was 47% for all the resected cases in Group 1 and 68% for Group 2. The 5-year survival rate was 61% for those who underwent a curative (radical) gastrectomy in Group 1, and 84% for those in Group 2. PMID- 1405438 TI - ["Sexuality in old age homes"]. PMID- 1405439 TI - [12000 nurses in Bonn]. PMID- 1405440 TI - [The federal office of the German Nurses' Association in Eschborn. Interview by Eva Maria Krampe]. PMID- 1405441 TI - [Report on the work of the Federal Secretariat]. PMID- 1405442 TI - [The federal office of the German Nurses Association in Neuwied]. PMID- 1405444 TI - [Facets of holistic medicine]. PMID- 1405443 TI - [Touching in everyday professional life is touching us--summary of a thesis. In the hands of nurses]. PMID- 1405445 TI - [A joyous hospice]. PMID- 1405446 TI - [What nurses can do. Pain therapy 2]. PMID- 1405447 TI - [To prevent intraoperative complications. Checking the quality of one's own work]. PMID- 1405448 TI - [Where the human and the technical conditions match]. PMID- 1405449 TI - [Nurses facing drug addiction and substance abuse. A decisive decennium]. PMID- 1405450 TI - [Colloquium at the 1992 ISPA: "Women, men, dependencies" "You will fill your role as a real woman..."]. PMID- 1405452 TI - [Image and identity of the aged. The quest for meaning]. PMID- 1405451 TI - [The nurse in front of alcohol dependent patients. What attitude to adopt?]. PMID- 1405453 TI - [Collaboration between hospitals and non-hospital nursing services. It also concerns children]. PMID- 1405454 TI - [Functional deglutition disorders: etiology, diagnosis and therapy]. PMID- 1405455 TI - [What are the advantages of patient education for asthma patients]. PMID- 1405456 TI - [Possibilities of physical therapy in acute arthritis]. PMID- 1405458 TI - [General stoma care. Basics]. PMID- 1405457 TI - [The role of pharmacies in the ambulatory care of stomas]. PMID- 1405459 TI - [Cystic fibrosis, a not very rare hereditary disease. Description, treatment possibilities and therapeutic concepts]. PMID- 1405460 TI - [30 questions about your professional behavior]. PMID- 1405461 TI - [Hand disinfection and hand washing]. PMID- 1405462 TI - [Samuel Hahnemann--the originator of homeopathic medicine]. PMID- 1405463 TI - Detection of extremely low levels of wild-type mitochondrial DNA in the liver of a patient with Pearson syndrome by a sensitive PCR assay. PMID- 1405464 TI - Detection of the A to G(3243) mutation of mitochondrial DNA in Japanese families with mitochondrial encephalomyopathies. PMID- 1405465 TI - Mitochondrial DNA deletion in an 8-year-old boy with Pearson syndrome. PMID- 1405466 TI - Vitamin-responsive pyruvate dehydrogenase deficiency in a young girl with external ophthalmoplegia, myopathy and lactic acidosis. PMID- 1405467 TI - Assessment of deficiencies of fatty acyl-CoA dehydrogenases in fibroblasts, muscle and liver. PMID- 1405468 TI - Gluconeogenesis and ketogenesis in perfused livers from short-chain acyl-CoA dehydrogenase-deficient mice. PMID- 1405469 TI - Long-chain 3-hydroxyacyl-CoA dehydrogenase in leukocytes and chorionic villus fibroblasts: potential for pre- and postnatal diagnosis. PMID- 1405470 TI - Genetic complementation analysis of mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency in cultured fibroblasts. PMID- 1405471 TI - Significance of bound glutarate in the diagnosis of glutaric aciduria type I. PMID- 1405473 TI - Paediatric cerebrotendinous xanthomatosis. PMID- 1405472 TI - A new case of succinyl-CoA: acetoacetate transferase deficiency. PMID- 1405474 TI - Bone dysplasia associated with phytanic acid accumulation and deficient plasmalogen synthesis: a peroxisomal entity amenable to plasmapheresis. PMID- 1405475 TI - Zellweger-like phenotype in two siblings: a defect in peroxisomal beta-oxidation with elevated very long-chain fatty acids but normal bile acids. PMID- 1405476 TI - Human dihydroxyacetonephosphate acyltransferase deficiency: a new peroxisomal disorder. PMID- 1405477 TI - Prenatal diagnosis of Canavan disease. PMID- 1405478 TI - Partial N-acetylglutamate synthetase deficiency: a new case with uncontrollable movement disorders. PMID- 1405479 TI - Screening for tetrahydrobiopterin deficiency in newborns using dried urine on filter paper. PMID- 1405480 TI - Suspected pterin-4a-carbinolamine dehydratase deficiency: hyperphenylalaninaemia due to inhibition of phenylalanine hydroxylase by tetrahydro-7-biopterin. PMID- 1405481 TI - Hyperphenylalaninaemia presumably due to carbinolamine dehydratase deficiency: loading tests with pterin derivatives. PMID- 1405482 TI - Screening for defects of dihydropyrimidine degradation by analysis of amino acids in urine before and after acid hydrolysis. PMID- 1405483 TI - Adenylosuccinase deficiency: a newly recognized variant. PMID- 1405484 TI - Lipid peroxidation in homocysteinaemia. PMID- 1405485 TI - Ischaemic forearm testing in a patient with Ca(2+)-ATPase deficiency. PMID- 1405486 TI - Statistical properties of the Michaelis-Menten equation and their implication for inborn errors of metabolism. PMID- 1405487 TI - Converging pathways in Alzheimer's disease. PMID- 1405488 TI - Biologic and clinical heterogeneity of lymphoproliferative diseases of peripheral mature T lymphocytes. PMID- 1405490 TI - Cellular tropism and localization in the rodent nervous system of a neuropathogenic variant of Friend murine leukemia virus. AB - BACKGROUND: We studied PVC-211 murine leukemia virus (MuLV) (1), a neuropathogenic variant of Friend MuLV, to determine its cellular tropism and distribution in the nervous system of infected rats and the factors that affected disease expression. EXPERIMENTAL DESIGN: Rats from five different strains and mice from 3 strains were inoculated intracerebrally or intraperitoneally from birth to 10 days of age and observed for signs of neurologic disease and tumors for 24 weeks. Nervous system pathology, MuLV gp70 expression, and virus production were evaluated weekly for 4 weeks after perinatal infection of Fisher (F344) rats. Blood-brain-barrier integrity and ultrastructure were evaluated in 21-day-old symptomatic infected rats. Microvessel and mixed glial cell cultures were prepared from brains of infected and uninfected 21-day-old F344 rats and evaluated for virus production, MuLV gp70 expression, and the presence of PVC-211 MuLV DNA. RESULTS: Tremor, ataxia, spasticity, and hindlimb weakness occurred in rats and mice as early as 3 weeks after neonatal infection. Severity, latency, and progression varied among mouse and rat strains but exposure to PVC-211 MuLV before 6 days of age was required for disease expression. Rapid PVC-211 MuLV replication in brain capillary endothelial cells (BCEC) early in the perinatal period was followed by widespread astrogliosis, neuropil vacuolation, and finally, neuronal degeneration in the spinal cord, brainstem, cerebellum, and subcortex. MuLV gp70 expression in vivo increased during infection, was restricted to BCEC, but was not associated with perivascular inflammatory infiltrates. BCEC cultured from microvessel preparations but not astrocytes or microglia in mixed glial cell cultures isolated from infected rats contained PVC 211 MuLV DNA, expressed MuLV gp70, and produced infectious virus. CONCLUSIONS: The rapid replication of PVC-211 MuLV that occurs in the nervous system of infected rodents is restricted to BCEC. These infected BCEC appear to play a critical role in initiating the astroglial response in this neurodegenerative process through mechanisms that remain to be defined. PMID- 1405489 TI - Beta protein precursor expression in human platelets and a megakaryocyte cell line. Possible implications for the origin of cerebral amyloidosis in Alzheimer's disease. AB - BACKGROUND: The origin of the amyloid beta protein (A beta) that is the main constituent of amyloid fibrils occurring in the senile plaques and cerebrovasculature of individuals afflicted with Alzheimer's Disease, Down's Syndrome, Hereditary Cerebral Hemorrhage with Amyloidosis--Dutch Type, and Sporadic Cerebral Amyloid Angiopathy, is central to the pathogenesis of these disorders. Evidence exists to support a neuronal and/or a vascular origin. We have reported that platelets may serve as one possible source of the A beta sequence via an intact, membrane-associated Beta Protein Precursor (beta PP) which is encoded by a platelet transcript (BBRC 173:1292-1298, 1990). EXPERIMENTAL DESIGN: Immunoaffinity chromatography and western blotting of extracted cellular proteins, polymerase chain reaction amplification of beta PP mRNA, fluorescence activated flow cytometric analysis, and confocal scanning laser microscopy have been employed to characterize the presence and distribution of thrombocytic beta PP. RESULTS: Immunoblot analysis with antibodies specific for the carboxyl-terminal end of beta PP indicates that platelets and the Dami megakaryocyte cell line express membrane-associated species of intact beta PP ranging in molecular weight from 110 to 140 kilodaltons (kd), as well as carboxyl terminal reactive forms ranging from 16 to 22 kd. Thrombin stimulation of platelets induces the release of five soluble beta PP species, which possess apparent isofocusing points in the range of 4.1-5.5. By contrast, extracts of peripheral blood mononuclear cells enriched by ficoll centrifugation, endothelial cells and a B cell line were not immunoreactive by western blot, even though beta PP transcripts could be amplified by polymerase chain reaction. The distribution of platelet beta PP was localized by flow cytometric analysis and scanning laser microscopy, using fluorescein-labeled antibodies. Study of the subcellular distribution of platelet beta PP indicates that these translation products are accumulated in discrete foci throughout the thrombocyte, possibly corresponding to secretory granules. CONCLUSIONS: The size of the carboxyl-terminal forms of beta PP indicate that the A beta sequence is present as a membrane associated constituent in unstimulated platelets, and may represent alternative pathways of beta PP processing. Cleavage or other abnormal processing of platelet-associated beta PP in Alzheimer's disease provides one mechanism whereby cerebral amyloid might derive from the circulation. PMID- 1405491 TI - Myocardial heterogeneity and regional variations in response to injury. AB - BACKGROUND: Different regional variations in the heart with respect to structure, function, and metabolism are known. However, regional heterogeneity with respect to histochemical localization of enzymes under normal as well as different pathologic conditions remain to be described. EXPERIMENTAL DESIGN: Histochemical localization of glycolytic, oxidative, and hydrolytic enzymes was done in right and left ventricles, atria, nodal tissue, and Purkinje system in isolated perfused rat hearts under control as well as different experimental conditions including calcium paradox, ischemia-reperfusion and oxygen-free radicals. RESULTS: Histochemical reaction for glycolytic enzyme glycogen phosphorylase as well as for acetylcholine esterase was more intense in the nodal tissue and Purkinje fibers, whereas oxidative enzymes showed intense reaction in the contractile cells of the ventricles. Calcium paradox caused more histochemical enzyme changes in the subepicardial layer. Ischemia reperfusion had more damaging effect in the subendocardial layer. Oxygen-free radicals caused transmurally focal injuries. This pattern of histochemical changes also correlated with ultrastructural injury in these regions. Ventricular muscle suffered marked decreases, whereas atrial muscle showed a relatively less decrease in different histochemical enzyme activities. Purkinje fibers were the least affected tissue in this respect. The differential changes were most sensitively reflected by glycogen phosphorylase followed by lactate dehydrogenase, alkaline phosphatase, isocitrate dehydrogenase and beta-hydroxybutyric dehydrogenase. CONCLUSIONS: Regional heterogeneity with respect to histochemical distribution of enzymes in a normal heart may have contributed to unique regional responses to different injuries, whereas transmural inhomogeneity in the ventricular response may have to do with the functional and/or metabolic transmural differences. PMID- 1405492 TI - Arteriopathy in macaques infected with simian immunodeficiency virus. AB - BACKGROUND: An arteriopathy characterized by intimal and medial thickening and fibrosis was seen in 19 of 85 rhesus monkeys infected with simian immunodeficiency virus (SIV), a lentivirus with morphologic, genetic, and biologic similarities to HIV-1 and HIV-2. EXPERIMENTAL DESIGN: All cases of simian AIDS in rhesus monkeys at the New England Regional Primate Research Center, resulting from either experimental or naturally acquired SIV infection, were retrospectively examined for evidence of histopathologic changes to the vasculature. Of the 85 SIV-related deaths recorded in the pathology files to date, tissues from 19 animals were chosen for further study because of thickening, disruption, inflammation, or other abnormality to any layer of the vascular wall. The lesion was characterized by special stains, immunoperoxidase procedures, and ultrastructural examination. RESULTS: Affected monkeys of both sexes varied in age from 4 months to 17 years at the time of inoculation and survived from 41 days to 4 years after infection. Pulmonary arteries were affected in all 19 animals, while vessels in other parenchymal organs were involved less frequently. In addition to sometimes marked intimal thickening with luminal occlusion, the internal elastic laminae were fragmented and interrupted. Seven of 19 animals had pulmonary thromboses with varying degrees of organization and recanalization. Immunohistochemical studies, special stains, and ultrastructural analyses revealed the thickened intimae to be composed predominantly of collagen, extracellular matrix, and smooth muscle cells. Ultrastructurally, endothelial cells from both early (no intimal thickening) and advanced lesions were plump, vacuolated, and often disorganized and detached from the subendothelial space. Increased numbers of macrophages (CD68+) were found in the adventitia and occasionally in the thickened intima and media. Rare, fully differentiated macrophages (CD68+, 25F9+) were demonstrated in lumina of affected vessels, some of which expressed p27 SIV gag protein. However, the lesion was not uniformly associated with localization of either viral protein or RNA at the site using immunohistochemistry or in situ hybridization, respectively. A similar arterial lesion has been described in children with AIDS. CONCLUSIONS: The morphologic findings in macaques and their similarity to arteriosclerotic changes induced by experimental endothelial damage in other species collectively suggest that arteriopathy in AIDS may represent a manifestation secondary to primary endothelial injury. PMID- 1405493 TI - Transforming growth factor-beta regulates increased ductus arteriosus endothelial glycosaminoglycan synthesis and a post-transcriptional mechanism controls increased smooth muscle fibronectin, features associated with intimal proliferation. AB - BACKGROUND: In previous studies we established that there are developmentally regulated increases in endothelial hyaluronan (HA) and heparan sulfate (HS), and smooth muscle cell fibronectin (FN) related to the formation of intimal cushions, structures essential to the postnatal closure of the ductus arteriosus (DA). In this report, we investigated the mechanisms underlying these features to ascertain whether they were independently or coordinately regulated. EXPERIMENTAL DESIGN: We determined by assessing HA polymer size and by pulse labeling with [3H]glucosamine whether the increased glycosaminoglycans (GAGs) incorporated in DA compared with aorta (Ao) endothelial cell matrices reflected increased synthesis of HA and HS rather than decreased degradation. We assessed whether transforming growth factor-beta (TGF-beta) may be responsible for the increased DA endothelial GAGs and smooth muscle FN production by confirming the presence of TGF-beta in DA tissue using immunohistochemistry and by assessing the effect of adding neutralizing antibodies to the cell cultures. We next determined whether the level of regulation of the increase in FN in DA smooth muscle cells was transcriptional or post-transcriptional by relating protein synthesis to steady state mRNA levels and to mRNA levels after serum stimulation. Using northern blot analyses with specific probes, we also explored the possibility that the FN produced by the DA and Ao was qualitatively different in the proportion of isoforms containing the V95+ region associated with secretion or the EIIIB+ region that has been related to migration. RESULTS: We observed that HA polymer size produced by DA and Ao endothelial cells was similar and we further verified using pulse labeling that the increase in DA compared with Ao endothelial GAGs reflected increased synthesis of HA and HS rather than decreased degradation. There was increased immunostaining for TGF-beta in DA compared with Ao tissue and we showed that TGF-beta neutralizing antibodies reduced synthesis of GAGs by the DA endothelial cells to the level of that seen in the Ao cells, but did not reduce DA smooth muscle cell FN synthesis. The increase in FN synthesis by DA compared to Ao smooth muscle cells was not associated with increased levels of steady-state mRNA for FN. Furthermore, following serum-stimulated increases in FN mRNA, the DA yielded greater amounts of FN protein compared to Ao smooth muscle cells. The increased FN production by the DA smooth muscle cells could not be attributed to a relative lack of degradation of FN protein or mRNA, or to qualitative differences which might influence secretion, as both cell types contained similar proportions of EIIIB+ and V95+ isoforms of FN. CONCLUSIONS: These results would suggest that, in contrast to the TGF-beta dependent increase in DA endothelial GAG synthesis, the increase in DA smooth muscle FN synthesis arises through differences in post-transcriptional regulation that are likely independent of TGF-beta. PMID- 1405494 TI - Immunomorphometric studies of proteinuria in individual nephrons of rats. AB - BACKGROUND: Heterogeneity of proteinuria among nephrons has been directly shown by micropuncture analysis of experimental models. Since the number of nephrons per kidney that are accessible for micropuncture is very small, we have developed a new immunomorphometric method for directly studying proteinuria in a much larger number of individual nephrons. This new method is based on the luminal surfaces of thick ascending limb of the loop of Henle (TAL) cells collectively functioning as an immunoabsorbent column for anti-Tamm-Horsfall protein antibodies that enter the urinary filtrate of that nephron. EXPERIMENTAL DESIGN: The distribution of luminal IgG deposits formed in TALs after injection of anti Tamm-Horsfall protein antibodies was studied in three models of experimental proteinuria in rats to define the relationship between the formation of luminal deposits and the overall level of albuminuria and to test the utility of this method in analyzing the heterogeneity of luminal deposits among nephrons in other models. RESULTS: A close relationship between the magnitude of albuminuria and the distances that luminal IgG deposits extended along the straight course of TALs in individual nephrons of rats injected with rabbit anti-Tamm-Horsfall protein antibodies was established in a model of proteinuria with a uniform pattern of glomerular hemodynamics, heterologous immune complex nephropathy in rats. In models with more heterogeneous glomerular hemodynamics, autologous immune complex nephropathy and aminonucleoside nephrosis, greater heterogeneity in luminal IgG deposit formation among nephrons was demonstrated. The distances that luminal IgG deposits extended along TALs was more variable in these models than in heterologous immune complex nephropathy rats with comparable levels of albuminuria. CONCLUSIONS: Variability in the distances that luminal IgG deposits extend along TALs reflects heterogeneity among nephrons. The luminal deposit technique provides a new means for direct analysis of variability of dysfunction in many individual nephrons not accessible to micropuncture. PMID- 1405497 TI - The importance of research in ambulatory generalist practices. PMID- 1405496 TI - Coopetition in rural health education: the South Carolina AHEC model. PMID- 1405495 TI - Chromogranin A, chromogranin B and secretogranin II mRNAs in the pituitary and adrenal glands of various mammals. Regulation of chromogranin A, chromogranin B and secretogranin II mRNA levels by estrogen. AB - BACKGROUND: The chromogranin/secretogranin (Cg/Sg) acidic proteins are widely distributed in vertebrate species. They are thought to play a role in hormone packaging within secretory granules, in hormone secretion, and serve as prohormones for various proteolytic cleavage products. The genes for most members of the Cg/Sg family have been cloned, so hybridization analysis can be used to analyze the distribution and regulation of Cg/Sg mRNAs in various vertebrate species. EXPERIMENTAL DESIGN: The method of in situ hybridization was used to localize chromogranin A, chromogranin B, and secretogranin II in adrenal and pituitary tissues from laboratory animals and from humans in order to analyze the distribution of various Cg/Sg mRNAs in these tissues. To gain some insight into the regulation and possible functions of specific Cg/Sg members, female rats were ovariectomized for different periods with and without estrogen replacement and the pituitaries were subsequently analyzed by in situ hybridization and Northern hybridization analyses. Combined ISH and immunohistochemistry were used to localize the specific cell types in normal rat pituitary that expressed the mRNA for chromogranin A, chromogranin B, and secretogranin II. RESULTS: All three Cg/Sg mRNAs were detected in pituitary and adrenal tissues of rats, mice, dogs, monkeys, and humans. Combined in situ hybridization and immunohistochemistry using rat pituitary revealed that the glycoprotein hormone-secreting cells expressed all three Cg/Sg mRNAs in approximately equal amounts. Ovariectomy followed by estrogen replacement resulted in decreased levels of CgA and SgII mRNAs. In contrast, the level of CgB mRNA, that was not changed by ovariectomy, was increased after estrogen treatment, probably secondary to prolactin cell hyperplasia. CONCLUSIONS: The three principal Cg/Sg mRNAs are present in the adrenal and pituitary of various vertebrates. Estrogen plays a significant role in regulating the mRNA levels of different Cgs/Sgs suggesting functional and regulatory differences in Cg/Sg proteins. PMID- 1405498 TI - South Carolina AHEC's student development and recruitment program: a model for increasing minority participation in the health profession. PMID- 1405499 TI - Preclinical primary care--preceptorships and the student health coalition. PMID- 1405501 TI - Academic/private practice partnerships in the USC family medicine junior clerkship. PMID- 1405500 TI - Development and implementation of a multi-site junior core clerkship in family medicine. PMID- 1405502 TI - Community-oriented primary care in a rural community: the Hamptom County project. PMID- 1405503 TI - The Winnsboro Rural Primary Care Education Project. University of South Carolina School of Medicine. PMID- 1405504 TI - Williamston--a model rural practice for resident education. PMID- 1405505 TI - Practice-based education for family medicine residents in Prosperity, Abbeville, and Ninety-Six. PMID- 1405506 TI - Physician recruitment and retention: AHEC's role. PMID- 1405507 TI - Changing medical education for tomorrow's practice. PMID- 1405508 TI - History of the South Carolina Area Health Education Consortium (S.C. AHEC). PMID- 1405509 TI - Blindness in South Carolina. AB - In less than 40 years the number of people aged 55 and older will constitute almost a third of the United States population. With the median age in South Carolina increasing, the incidence of visual impairment and blindness will rise. Most of the leading causes of blindness in South Carolina are age related. Most of these causes can be prevented or treated resulting in the preservation of functional vision. By increasing public awareness of blindness prevention opportunities, a significant reduction in blindness in South Carolina can be attained. By eliciting the help of all health professions in South Carolina the incidence of visual impairment/blindness can be reduced. PMID- 1405510 TI - Laparoscopic-assisted vaginal hysterectomy: a continuing evolution of surgical technique. PMID- 1405511 TI - Should South Carolina physicians incorporate their practices? PMID- 1405512 TI - William Osler and medical societies. PMID- 1405513 TI - Robert B. Taft, M.D., (1899-1951) and his "Radium Hound". PMID- 1405514 TI - Aging Koreans' perceived conflicts in relationships with their offspring as a function of age, gender, cohabitation status, and marital status. AB - The Youn Scale was used to assess aging Koreans' perceived conflicts in relationships with their adult offspring. The sample consisted of 623 elderly Koreans between the ages of 55 and 84 years. Results indicated that aging Koreans experienced significantly more conflicts in their relationships as they grew older. There were also differences in the perceptions of problems in relationships with their offspring between those who lived together with their adult children and the those who did not, and also between those who were married and those who were single. The findings imply that aging Koreans want to have qualitatively better (i.e., warmer and closer) relationships with their offspring, regardless of their bereavement status and cohabitation status. PMID- 1405516 TI - Hostile press measure of fear of failure and its relation to child-rearing attitudes and behavior problems. PMID- 1405517 TI - Cultural variations in sex typing: a comparison of students in the United States, Germany, and India. PMID- 1405515 TI - Gender and self-disclosure revisited: personal and contextual variations in self disclosure to same-sex acquaintances. AB - Male and female American students who differed in masculinity and in femininity self-disclosed to a same-sex stranger in contexts that made either social/expressive motives or instrumental motives salient. The results were consistent with the primary assertion that measures of sex role identity are better predictors of contextual variations in self-disclosure than is sex per se. Sex consistently failed to predict subjects' willingness to self-disclose, both within and across contexts, whereas femininity promoted self-disclosure in the context that was clearly social and expressive in character. Although masculinity failed to exert the expected facilitative impact on self-disclosure within the instrumental context, it nonetheless influenced the results; androgynous subjects, who scored high in both masculinity and femininity, were more self revealing across contexts than was any other group. PMID- 1405518 TI - An experimental comparison of two AIDS prevention interventions among young Zimbabweans. PMID- 1405519 TI - Environmental concern and cooperative-competitive behavior in a simulated commons dilemma. AB - Commons-dilemma simulation games are designed to examine behavior associated with preservation and destruction of slowly regenerating natural resources. In Experiment 1, 120 introductory psychology students in the United States were assigned to high- or low-environmental-concern conditions based on a median split of their scores from a pretest. They then played either a points game, in which they selected numerical points from a slowly regenerating pool, or a tree game, in which they harvested trees from a jointly managed forest. After the game, subjects were asked to sign a petition for an environmental cause, to participate in a litter pick-up, and to participate in a recycling drive. Neither environmental concern nor proenvironmental behaviors were related to commons dilemma performance. In Experiment 2, 57 other introductory psychology students were assessed on environmental concern and Machiavellian personality, size of other players' harvesting choices, and other players' altruistic choices, all correlated with subjects' outcomes in the game. Overall, cooperation and competition were more important than environmental concern in predicting behavior in the commons dilemma simulation game. PMID- 1405520 TI - Cognitive profiles of Japanese and Canadian kindergarten and first-grade children. AB - Japanese kindergarten and first-grade children were given the Canadian Cognitive Abilities Test (CCAT), with slight cultural modifications. Widely used in Canadian and American schools, the CCAT consists of three batteries: verbal, quantitative, and nonverbal. The sample consisted of 454 Japanese children (234 boys, 220 girls). Results were examined by 3-month age intervals (chronological age range, 60 to 87 months of age). Subjects' scores were compared with CCAT norms, based on the performance of 3,500 Canadian children at each age level. On each battery, the Japanese children outperformed their Canadian counterparts, but the differential was most apparent on the verbal battery. Moreover, on the nonverbal battery for kindergarten Japanese children (ages 60 to 72 months), significant differences appeared only with the 60- to 63-month age cohort. Results indicate that the higher achievement of Japanese children was apparent by the time they entered kindergarten and that higher Japanese educational productivity could not be solely attributed to schooling effects. Furthermore, the data indicate that the early academic advantage of Japanese children may widen as they progress through their first year of school. (Longitudinal replication studies are suggested for examination of the long-range impact of the early cognitive advantage of Japanese children.) PMID- 1405521 TI - Evaluation of a rapist as a function of expressed intent and remorse. AB - Two studies were conducted to examine the effects of expressed versus denied intent and remorse on evaluation of a rapist. In both studies, the rapist was evaluated more negatively and was assigned a longer prison sentence when expressing rather than denying intent. The rapist received more favorable evaluations when expressing rather than denying remorse. Manipulation of the rapist's expressed remorse did not significantly affect the recommended prison sentence. However, the recommended prison sentence did correlate significantly with participants' perceptions of the rapist's remorse. A multiple regression analysis indicated that recommended prison sentence could be best predicted by attributions of cause, intent, and remorse. The results were related to a growing body of research on accounting strategies, responsibility, and excuse making. PMID- 1405522 TI - Loneliness in middle childhood. PMID- 1405523 TI - Relationship between parental education and academic achievement of Xhosa children from broken and intact families. PMID- 1405524 TI - Consistency in cognitive appraisal of a stressful event over time. PMID- 1405525 TI - Children's reactions to faces before and after minor facial surgery. PMID- 1405526 TI - The effects of initial level of self-esteem, gender, and task outcome on causal attribution and affective arousal. PMID- 1405528 TI - The relationship of vallecular residue to oral involvement, reduced hyoid elevation, and epiglottic function. AB - The purpose of this investigation was to identify certain variables that may result in vallecular residue after swallowing. The relationship between vallecular residue and oral-stage dysphagia, reduced hyoid elevation, and movement of the epiglottis was assessed in 330 patients referred to the speech pathology section for evaluation of oropharyngeal swallowing function. Patients with vallecular residue were more likely to have oral involvement or deviant epiglottic function, characterized by an absence of epiglottic inversion or incomplete inversion, than patients without vallecular residue. Although the primary focus of the study was between vallecular residue and the other select variables, the interrelationships among the three other variables were also studied. Patients with deviant epiglottic function were more likely to have oral involvement, reduced hyoid elevation, or vallecular residue than patients without deviant epiglottic function and patients with reduced hyoid elevation were more likely to have oral involvement than those with normal hyoid elevation. Multivariate analysis revealed that the relationship between oral involvement and deviant epiglottic function, present in the bivariate analysis, was not significant when controlling for other relationships in the model. The relationship between primary medical diagnostic category and the presence/absence of vallecular residue as well as the other dichotomous variables varied between and within diagnostic categories. PMID- 1405527 TI - Quantitative description of the dysarthria in women with amyotrophic lateral sclerosis. AB - Speech intelligibility and its phonetic and acoustic correlates were studied in a group of 10 women with amyotrophic lateral sclerosis (ALS). Intelligibility assessment with a word-identification test indicated that the most disrupted phonetic features pertained to velopharyngeal valving, lingual function for consonant contrasts of place and manner, and syllable shape. An acoustic signature analysis based on trajectories of the first and second formants in selected monosyllabic test words revealed that the mean slope of the second formant (F2) was reduced compared with that of a normal geriatric control group. This F2 slope reduction is interpreted to reflect loss of lingual motoneurons. Acoustic measures of phonatory function for sustained vowel prolongation demonstrated abnormalities in fundamental frequency, perturbations of frequency (jitter) and amplitude (shimmer), and signal-to-noise ratio. The data for women with ALS are compared with data for a normal geriatric control group of women and with data for a group of 25 men with ALS (Kent et al., 1990). Although the overall ranking of errors was similar for males and females with ALS, men were more likely to have impairments of voicing in syllable-initial position. PMID- 1405529 TI - Parent verbal interactions and speech rate: a case study in stuttering. AB - This single-case study of indirect stuttering treatment is intended to identify variables for further research. The study used post hoc analyses of changes in parent speech variables and changes in the child's stuttering. The analysis was conducted in two parts. Study I examined the relationships between the child's percent syllables stuttered and the parents' speech rates and percentages of nonaccepting statements, interruptions, questions, nonaccepting questions, and talk time. The only parent variable significantly correlated with the child's stuttering was the mother's speech rate. In Study II the child's percent syllables stuttered were subdivided into primary (effortless) and secondary (tense) stuttering. Each category was then correlated with the parent variables examined previously. Results suggested that the parent variables that were significantly related to the child's primary stuttering were not the same as those significantly related to her secondary stuttering. Specific parent variables are suggested for further study. PMID- 1405530 TI - A longitudinal study of stuttering in children: a preliminary report. AB - The objectives of this pilot study were to establish methods for longitudinal research of stuttering in children and to provide preliminary data on the variations that occur in disfluencies during the developmental course of stuttering. Twenty-seven preschool-aged children were followed for a minimum of 2 years shortly after they began stuttering. Tape-recorded speech samples were obtained from the children at several intervals during this period. The number of various types of disfluencies was counted in the speech samples obtained in each testing period. Twenty-one children continued to be followed for varying periods of up to 12 years. Eighteen of the 27 subjects received a few speech treatment sessions during the initial period of the study, whereas 9 children did not receive direct treatment. Results indicated that for the two subgroups there was a marked deceleration over time in the mean frequency of stuttering-like disfluencies. Individual subjects' data showed considerable variability in the longitudinal development of disfluency but most subjects followed the patterns of the group means. Much of the reduction took place during the early stage of the disorder, especially near the end of the first year post-onset. There were indications that group differences between chronic and recovering stutterers become distinct by approximately 20 months post-onset. PMID- 1405531 TI - Vocal tract steadiness: a measure of phonatory and upper airway motor control during phonation in dysarthria. AB - Acoustic analyses of upper airway and phonatory stability were conducted on samples of sustained phonation to evaluate the relation between laryngeal and articulomotor stability for 31 patients with dysarthria and 12 non-dysarthric control subjects. Significantly higher values were found for the variability in fundamental frequency and format frequency of patients who have Huntington's disease compared with normal subjects and patients with Parkinson's disease. No significant correlations were found between format frequency variability and the variability of the fundamental frequency for any subject group. These findings are discussed as they pertain to the relationship between phonatory and upper airway subsystems and the evaluation of vocal tract motor control impairments in dysarthria. PMID- 1405532 TI - Locus equations as an index of coarticulation for place of articulation distinctions in children. AB - Locus equations were investigated as a phonetic index for children's production of stop + vowel tokens. Locus equations are straight-line regression fits to data points formed by plotting onsets of F2 transitions along the ordinate and their corresponding midvowel nuclei along the abscissa. Such functions for adult speech have been found to be extremely linear with slope and y-intercept values contrastively distinctive across place of articulation. Sixteen children, aged 3 5 years, produced /bVt/, /dVt/, and /gVt/ tokens embedded in a carrier phrase and repeated in randomized order a minimum of three times. Six medial vowel contexts were used [i, I, ae, [symbol: see text], a, u]. Both individual and group mean scatterplots were extremely linear and highly remniscent of adult prototypes. While labial and velar slopes exhibited some degree of overlap, labial versus alveolar and alveolar versus velar slopes were significantly different. All y intercepts as a function of place of articulation were significantly different. Compared to adult norms, intersubject variability of slope and y-intercept ranges were greater for children. Locus equations can provide a phonetic descriptor for a child's attainment of stop place categories seeking to achieve the adult standard of a balance between coarticulatory adjustments and contrastive distinctiveness. PMID- 1405533 TI - Onset of stuttering in preschool children: selected factors. AB - This investigation provides updated information on the onset of stuttering, explores variations in the onset, and studies possible relationship of stuttering onset to the factors of age, gender, familial history, severity, and stress. Data were obtained for 87 preschool children through parent interviews, using a standardized questionnaire. Interviews were conducted within 12 months after the disorder was first diagnosed. Results for selected items indicated that onset tended to occur at an earlier age than was previously thought and was sudden and/or severe in a substantial number of cases. Physical or emotional stress and familial histories of stuttering were reported for many of the participating children. A significant gender factor was found. About twice as many boys as girls stuttered and girls began stuttering at a significantly earlier age. There was a positive relationship between severe stuttering and sudden onset. Several other tendencies for relationship between factors were either weak or not significant for the present sample size. The findings are discussed with special reference to the possible relationship between stuttering onset and maturational processes and the possible contribution of data on onset to the differentiation of stutterers. PMID- 1405534 TI - The relationship between communication attitude, anxiety, and depression in stutterers and nonstutterers. AB - People who stutter are frequently viewed as more anxious than nonstutterers and as being depressed. Further, a strong and pervasive stereotype is held by nonstutterers that people who stutter are guarded, nervous, and tense. This study examined self-perceptions of general state and trait anxiety, depression, and communication attitude in matched groups of stutterers and nonstutterers. Results refute the assertion that people who stutter are more anxious or depressed than those who do not. Anxiety and depression are not related to self-ratings of stuttering severity. Communication attitude is negative for this group of people who stutter and becomes increasingly negative as self-ratings of stuttering become more severe. People who stutter, grouped by severity rating, differed in the strength of the relation between measures of communication attitude, anxiety, and depression. Findings suggest that the anxiety of people who stutter is restricted to their attitude towards communication situations and that it is a rational response to negative communication experiences. PMID- 1405535 TI - Constancy of interstress intervals in the fluent speech of people who stutter during adaptation trials. AB - The constancy of interstress intervals (ISIs) was studied in the fluent speech of 2 people who stutter during five adaptation trials. Counter to prediction, ISI constancy did not improve as an accompaniment to the reduction of stuttering from Readings 1-5. Overall, the subjects' ISIs were substantially more variable in duration than those of 2 nonstutterers. This was accounted for by the subjects' unusually long ISIs in utterances that placed greater demands on speech motor control processes. Implications for impairment source factors in stuttering are discussed. PMID- 1405536 TI - Did primitive man really talk like an ape? PMID- 1405537 TI - Commentary on "A theory of neuropsycholinguistic function in stuttering". PMID- 1405538 TI - Factors underlying neuropsychological test performance in chronic severe traumatic brain injury. AB - The neuropsychological test performance of subjects with traumatic brain injury (TBI) of the closed head type was investigated using a test battery consisting of traditional clinical instruments with expanded language measures. TBI subjects were specifically selected to include only those with a pattern of predominantly diffuse cerebral injury to allow conclusions regarding language performance in the absence of focal aphasia-producing lesions. Factor analysis of the test scores resulted in the extraction of three interpretable factors associated with performance on this battery: perceptual, general language, and mental efficiency. The results were compared to those obtained in previous factor-analytic studies of brain-damaged subjects, revealing patterns for the language/verbal subtests that diverged from those observed formerly. Two explanations are considered for these findings, the first interpretation centering on the notion of select impairments to specific cognitive processes and the second relating to impairments in the capacity to allocate resources effectively. PMID- 1405539 TI - Residual effects of preschool phonology disorders in grade school, adolescence, and adulthood. AB - This study used a cross-sectional design to examine the performance of people with a history of a preschool phonology disorder on measures of phonology, reading, and spelling at preschool age (n = 20), grade school age (n = 23), adolescence (n = 17), and adulthood (n = 17). Results showed that at each age group, subjects with a history of a disorder performed more poorly than control subjects matched for age, sex, and socioeconomic status in all domains. Comparisons across each successive age group revealed a higher performance on measures from preschool to grade school age, and a smaller but steady improvement from grade school age to adolescence to adulthood. Subjects with a history of other language problems, in addition to the phonology disorder overall, performed more poorly than subjects with a history of a preschool phonology disorder alone on the reading and spelling measures. These findings suggest that remnants of a preschool phonology disorder are detectable past grade school age and into adulthood. PMID- 1405540 TI - Diagnosing specific language impairment in adults for the purpose of pedigree analysis. AB - Two sets of diagnostic measures were administered to a group of 35 adults with well-documented histories of specific language impairment and to a control group of 35 normal language users. These measures involved the comprehension and production of words and sentences in formal and spontaneous speaking activities as well as measures of verbal memory and auditory temporal perceptual ability. One set of tasks was administered in a standard face-to-face setting and the other set was given over the telephone. Multivariate and univariate tests indicated that the adults with a history of specific language impairment performed more poorly on all tasks administered. A discriminant analysis of the two sets of measures indicated that four measures in each set identified language impaired individuals with 97% accuracy for the face-to-face battery and 95% accuracy for the telephone battery. These results suggest that it should be possible to diagnose specific language impairment in the adult family members of children with specific language impairment and therefore permit accurate construction of pedigrees for specific language impairment. PMID- 1405541 TI - Message-encoding techniques for augmentative communication systems: the recall performances of adults with severe speech impairments. AB - This study investigated the cognitive and linguistic processing demands of message-encoding techniques used to retrieve prestored messages from computer based augmentative communication systems. Twelve physically disabled adults with severe speech impairments participated in six counterbalanced experimental conditions, consisting of three encoding techniques (salient letter, letter category, and iconic codes), each in a personalized condition in which subjects selected their own codes and in a nonpersonalized condition in which codes were preselected by a clinician. In each of the experimental conditions, the subjects participated in five learning and testing sessions. During these sessions, the subjects learned the codes for lists of 80 messages, half of which involved concrete referents and half abstract concepts. Results indicated that the subjects were more accurate in recalling the codes to retrieve preprogrammed messages when using the two letter encoding techniques than when using the iconic technique. No reliable differences were found between recall performances with personalized codes and with nonpersonalized ones for any of the three encoding techniques. Code recall improved consistently across the series of learning sessions; there were no significant differences in the rates of learning across the encoding techniques. Subjects were found to be more accurate at recalling the codes to retrieve concrete messages than those to retrieve abstract messages. PMID- 1405542 TI - Instructing facilitators to support the communication of people who use augmentative communication systems. AB - A single-subject multiple-baseline design, replicated across three dyads, was used to examine the efficacy of instructing facilitators (i.e, significant others) to promote communication with people who use augmentative and alternative communication (AAC) systems. Facilitators were instructed in four 1-hour sessions to decrease their conversational control and provide more opportunities for the participants using AAC systems to communicate. Following instruction, facilitators decreased their rates of turn-taking and initiations and increased the proportion of turns that were responsive. Participants using AAC systems increased the frequency of their initiations. Following intervention, turn-taking and initiation patterns in the dyads were more reciprocal. Generalization occurred to the natural environment. Results suggest that facilitator instruction is an effective and efficient means of promoting greater participation in daily interactions by people who use AAC systems. PMID- 1405543 TI - Sources of variability in speechreading sentences: a generalizability analysis. AB - Generalizability theory (Cronbach, Gleser, Nanda, & Rajaratnam, 1972) was used to estimate the percentage of variance explained by three sources of variability in speechreading sentences: the subject, the talker, and the sentence materials. Videodisc recordings of the 100 CID Everyday Sentences (Davis & Silverman, 1970), spoken by a male and a female talker, were presented to 104 subjects with normal hearing. For performance on individual sentences (total number of words correct), the most important systematic sources of variability were the sentence (26.3%), the speechreader (10.5%), the talker (4.9%), and the interaction of talker and sentence (5.1%). Residual error accounted for 51.2% of the variance. Generalizability functions are presented, as a function of test length, for five models of test administration and interpretation. For 10-, 50-, and 100-item lists, generalizability is predicted to be .70, .92, and .96, respectively, for a single talker. Psychometric characteristics of these recordings of the CID sentences are also presented. PMID- 1405545 TI - The clinical utility of the P3 AERP in children with auditory processing disorders. AB - This study investigated whether the P3 AERP could be used to reflect behavioral changes resulting from therapeutic intervention in a group of children with central auditory processing disorders (CAPDs). Results showed a significant decrease in P3 latency, along with a significant increase in P3 amplitude, following a structured treatment program. No changes occurred in either the CAPD control group or in the normal control group. These results suggest that the P3 AERP latency and amplitude measures are sensitive to changes in clinical status following a treatment program. PMID- 1405544 TI - Age-related differences in processing dynamic information to identify vowel quality. AB - This study examined age-related differences in the use of dynamic acoustic information (in the form of formant transitions) to identify vowel quality in CVCs. Two versions of 61 naturally produced, commonly occurring, monosyllabic English words were created: a control version (the unmodified whole word) and a silent-center version (in which approximately 62% of the medial vowel was replaced by silence). A group of normal-hearing young adults (19-25 years old) and older adults (61-75 years old) identified these tokens. The older subjects were found to be significantly worse than the younger subjects at identifying the medial vowel and the initial and final consonants in the silent-center condition. These results support the hypothesis of an age-related decrement in the ability to process dynamic perceptual cues in the perception of vowel quality. PMID- 1405546 TI - Performance over time of congenitally deaf and postlingually deafened children using a multichannel cochlear implant. AB - The speech perception performance of 10 congenitally deaf and 3 postlingually deafened children who received the Cochlear Corporation multichannel cochlear implant was examined and compared. The children were tested preimplant and at 6 month intervals up to 2 years using the Monosyllable-Trochee-Spondee test (MTS), the Word Intelligibility by Picture Identification test (WIPI), and Phonetically Balanced Kindergarten (PB-K) or Northwestern University List 6 (NU-6) word lists. The postlingually deafened children exhibited significantly improved performance on open- and closed-set tests of word recognition after 6 months of implant use, a pattern similar to that of postlingually deafened adult implant users. In contrast, the congenitally deaf children did not exhibit measurably improved performance on speech perception tests until after 12 months or more of implant use. With as much as 18-24 months of use, however, some congenitally deaf children demonstrated limited open-set word recognition. PMID- 1405547 TI - The development and cross-validation of a self-report inventory to assess pure tone threshold hearing sensitivity. AB - Previous attempts to assess hearing loss by means of self-report survey items have shown only low to moderate correlations with actual audiometric measures, probably because these attempts used items with high face validity rather than laboratory-tested validity. Beginning with a pool of 108 items used with 384 individuals, we developed a self-report inventory (see Appendix) suitable for group testing or survey administration, which appears to have high correlation with pure-tone hearing thresholds. The inventory was then cross-validated against laboratory audiometric measures in a separate sample of 422 subjects. The resulting 12-item Hearing Screening Inventory (HSI) was shown to be reliable with an internal consistency coefficient (alpha) of 0.89 and test-retest stability coefficient of 0.88. The correlation between pure-tone hearing thresholds in the better ear and the HSI scores for the combined samples was r = 0.81. The correct classification rate for the HSI was 92.1% for a low fence of 25-dB hearing level and 93.4% for a high fence of 55-dB hearing level. A conversion equation with estimated variability is also provided for point estimates of pure-tone hearing thresholds from the HSI scores. A copy of the inventory and scoring procedure is appended to this report. PMID- 1405548 TI - Some psychometric properties of the Test of Basic Auditory Capabilities (TBAC). AB - This study examined some psychometric properties of the Test of Basic Auditory Capabilities (TBAC). Two experiments are described that evaluate the psychometric functions and the test-retest reliability of the tests comprising the TBAC. The psychometric functions were established for young listeners with normal hearing and the test-retest reliability was evaluated both with young listeners with normal hearing and elderly listeners with hearing impairment. Results indicate that maximum scores on the TBAC are reached at presentation levels of at least 65 75 dB SPL. In addition, the reliability analyses indicate that the TBAC is a reliable measure for both young listeners with normal hearing and elderly listeners with hearing impairment when at least one practice test is given. PMID- 1405549 TI - Equivalent ear canal volumes in children pre- and post-tympanostomy tube insertion. AB - Pre- and postoperative equivalent ear canal volume measures were obtained from a group of 334 children ranging in age from 6 weeks to 6.7 years. The purpose of the study was to develop volumetric guidelines for the determination of tympanostomy tube patency. For children 4 years and older, almost no ambiguity existed in making this determination accurately. For younger children, the pre- and postoperative distributions overlap. A criterion value of greater than or equal to 1.0 cm3 as an indicator of a tympanic membrane perforation appears to yield the lowest possible error rate. When both pre- and postoperative measures are available, a difference of greater than or equal to 0.4 cm3 can be used in conjunction with the absolute value to identify a patent tympanostomy tube. PMID- 1405550 TI - Detection and recognition of stop consonants by normal-hearing and hearing impaired listeners. AB - This study examined the possibility that hearing-impaired listeners, in addition to displaying poorer-than-normal recognition of speech presented in background noise, require a larger signal-to-noise ratio for the detection of the speech sounds. Psychometric functions for the detection and recognition of stop consonants were obtained from both normal-hearing and hearing-impaired listeners. Expressing the speech levels in terms of their short-term spectra, the detection of consonants for both subject groups occurred at the same signal-to-noise ratio. In contrast, the hearing-impaired listeners displayed poorer recognition performance than the normal-hearing listeners. These results imply that the higher signal-to-noise ratios required for a given level of recognition by some subjects with hearing loss are not due in part to a deficit in detection of the signals in the masking noise, but rather are due exclusively to a deficit in recognition. PMID- 1405551 TI - Frequency-importance functions for words in high- and low-context sentences. AB - The relative importance and absolute contributions of various spectral regions to speech intelligibility under conditions of either neutral or predictable sentential context were examined. Specifically, the frequency-importance functions for a set of monosyllabic words embedded in a highly predictive sentence context versus a sentence with little predictive information were developed using Articulation Index (AI) methods. Forty-two young normal-hearing adults heard sentences presented at signal-to-noise ratios from -8 to +14 dB in a noise shaped to conform to the peak spectrum of the speech. Results indicated only slight differences in 1/3-octave importance functions due to differences in semantic context, although the crossovers differed by a constant 180 Hz. Methodological and theoretical aspects of parameter estimation in the AI model are discussed. The results suggest that semantic context, as defined by these conditions, may alter frequency-importance relationships in addition to the dynamic range over which intelligibility rises. PMID- 1405552 TI - Accuracy of intramedullary alignment in total knee replacement. AB - The accuracy of a system of intramedullary alignment using 6 mm rods was assessed in 100 patients undergoing total knee replacements. Post-operative, full length weight-bearing X-rays were used; the mechanical axis from head was used as the reference axis. The method of calculating the errors produced by flexion and rotation of the limb in relation to the X-ray beam is described, the mean deviation from the mechanical axis in 100 cases being 0.67 degrees valgus with a standard deviation of 2.47 degrees. The maximum error was 6.68 degrees valgus and 4.62 degrees varus. The purpose of this study is twofold, first to assess the accuracy of this system of intramedullary alignment and, second, to develop a method of correcting for apparent radiological misalignment using standard radiographic equipment. PMID- 1405553 TI - An experimental apparatus for the simulation of three-dimensional movements in orthodontics. AB - An apparatus for the study of three-dimensional force systems and the resulting movements during orthodontic treatment is presented. The instrument consists of two force-torque transducers which are capable of recording both forces and torques simultaneously, in all spatial directions. Each sensor has a measuring range of 15N (450 Nmm) and a resolution of 0.02 N (0.5 Nmm) and is mounted on a set of three translational and three rotational stages driven by stepping motors. Positioning accuracy is in the range of 1 micron and 0.01 degrees respectively. The apparatus is computer controlled and supported by comprehensive software. PMID- 1405554 TI - Aseptic loosening of the femoral component in cemented total hip replacement. AB - The purpose of this study was to identify factors which predispose to aseptic loosening of the femoral component in cemented total hip replacement. Its design was based on rigid selection criteria, so that successful and loose replacements which employed the same surgical technique were compared. Measurements of patient anatomy and of the insertion of the femoral component were made, by an accurate computer technique, on initial post-operative radiographs. Loosening was associated with heavier patients with a wider medullary canal which was flared proximally. This difference in anatomy led to differing distributions of cement in the successful and loose replacements. Medial cement-bone demarcation, at the mid-stem level, was also associated with loosening. These findings indicate the importance of optimizing the size of the prosthesis with respect to the femoral morphology. PMID- 1405555 TI - Oxygen exchange mechanisms in the human placenta: mathematical modelling and simulation. AB - An exact knowledge of the human fetus's respiratory mechanisms is still lacking; in particular, the role of human placental anatomy in oxygen exchange has not yet been studied satisfactorily. In this paper, a mathematical model of placenta as O2 exchanger between maternal and fetal blood was developed; it led to the solution of equations based upon diffusion laws and the haemoglobin dissociation curve. Particular care was taken to represent the regimen of laminar motion or whirling into the capillaries. Theoretical results were compared, under physiological conditions, with clinical data relating to fetal oxygenated blood p O2 during the second half of gestation (20th-38th weeks), and a theoretical confirmation of the decreasing effectiveness of placental O2 exchange during gestation was found. The result was able to describe oxygen exchange during a period in which clinical data are scanty (23rd-30th weeks). The effects of some pathological events on O2 exchange were then simulated. Model parameters were changed to simulate the effects on oxygen exchange of some typical pathological variations of placental anatomical features: exchange surface thickness and capillary length. The curves obtained for different gestational ages can easily be correlated with echographic measures of placental volume and dimensions of placental capillaries. The results also show that the human placenta is more sensitive to pathologies when it is young than at term of gestation. PMID- 1405556 TI - Pulse transmission and impedance characteristics of a non-uniform circulatory model. AB - In recent years, the technique of non-uniform transmission lines has been utilized in the synthesis of lines feeding antennae from transmitters, thereby maintaining matching over a wide band of frequencies and with varying load. For this reason, an electrical model based on that technique stems from the resemblance between the two systems: in both the feeding medium is non-uniform, and it is necessary to maintain a good response over a wide range of frequencies. Our non-uniform transmission line model of the arterial system, introduced in an earlier publication, supplies comprehensive answers to many questions dealing with the research into this system. Whereas in our earlier model the ohmic resistance R was considered small and not considered in the calculations, it is included in the present study. We have calculated the variation of the input impedance with the frequency and distance from the source, the effect of occluded main branches, augmentation of the pressure wave, the relationship between body size and heart rate and the matching of impedances at large bifurcations. We found that our calculated results agree very well with the quantitative results measured by other investigators in the field. PMID- 1405557 TI - Experimental results on the rewarming of a cryopreserved organ phantom in a UHF field. AB - We describe a UHF rewarming system which has been used to measure warming rates, and particularly the uniformity of warming on three orthogonal axes, in a rabbit kidney phantom 36 mm in diameter. The stabilizing effect is demonstrated of using an E-field directed along the temperature gradient (or normal to any surface of dielectric discontinuity). One hot spot remains unaccounted for. The average warming rates and power dissipation are related to the volumetric heat capacity of the phantom material at -30 degrees C. PMID- 1405558 TI - Development of a digital adaptive control system for PO2 regulation in a membrane oxygenator. AB - Regulation of gas exchange in artificial lungs (oxygenators) during cardiopulmonary bypass is normally achieved by manual control of the gas composition and flow in response to intermittent sampling of the arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2). Manual control often results in abnormal blood gases which have been implicated in patient morbidity as well as influencing perfusion safety. Fine control of PaO2 and PaCO2 may be achieved by a combination of an in-line blood gas monitoring system and a membrane type oxygenator which is automatically regulated. The overall dynamics of the oxygenation process and control system components are complex and have nonlinear, multivariable and time-varying characteristics. Consequently, an adaptive control system approach is necessary. The implementation of a digital self-tuning control regime for PaO2 is described here. The controller is based on an explicit Linear Quadratic Gaussian (LQG) self-tuning control design which is presented using a polynomial equation approach. The controller performance was investigated in in vitro experiments. The self-tuner performed satisfactorily with various sensor/oxygenator combinations for blood flow and temperature load disturbances. In contrast, a nonadaptive (proportional-integral, PI) type of control system was found to be unsuitable. PMID- 1405559 TI - An optical three-dimensional technique for topographical descriptions of surgical implants. AB - The purpose of this study was to develop a noncontacting optical method for the topographical description of surfaces. The method is suitable for all types of surgical implants, including threaded ones. The TopScan 3D system employs a scanning spot and a stationary object at a relatively large working distance to enable proper object alignment, and the depth discrimination property of confocal laser scanning microscopy forms the basis of its surface profiling ability. Scanning is achieved by precision movement of the microscope objective along three orthogonal axes (X, Y, Z). Three-dimensional surface topographical maps are produced by performing a series of parallel XZ scans in Y steps. Eighty seven screw-shaped titanium implants were divided into five groups each with a different surface roughness. The five groups were obtained by varying the size of the blasting particles and by leaving one group 'as-machined'. By using the TopScan 3D approach, we were able to calculate different kinds of surface roughness parameters and to produce visual images from the groups. As expected, the surfaces blasted with large particles showed higher values for the surface parameters than those blasted with smaller particles; the latter had higher values than the 'as-machined' screws. PMID- 1405560 TI - Image processing system for interpreting motion in American Sign Language. AB - In this paper, an image processing algorithm is presented for the interpretation of the American Sign Language (ASL), which is one of the sign languages used by the majority of the deaf community. The process involves detection of hand motion, tracking the hand location based on the motion and classification of signs using adaptive clustering of stop positions, simple shape of the trajectory, and matching of the hand shape at the stop position. PMID- 1405561 TI - Development of a humidifier for patient ventilation using a semi-permeable tube to minimize system condensate. AB - Condensation in the external airways of patient ventilation systems using conventional warm-water humidifiers increases the risk of bacterial contamination. Condensate formation can be reduced by heating the external airway and reducing the length of tubing between the patient and humidifier. The method described incorporates the humidifying element within the interconnecting tubing itself. Air is supplied through two semi-permeable tubes, of polytetrafluoroethylene, which are encased in an outer shell. A warm-water jacket is maintained in the shell; this is the source of heat and water vapour which diffuses through the semi-permeable tube wall and into the patient's air supply. An evaluation of performance and an initial clinical trial are reported. PMID- 1405562 TI - Is fetal heart rate monitoring sufficiently sensitive to detect changes during labour? AB - Although fetal monitoring is a common clinical procedure, there is little quantitative evidence that it can detect changes occurring during labour. We present quantitative data comparing the first and second stage of labour, from 21 labours resulting in a normal fetal outcome. A range of fetal heart rate variables was calculated from the output of a fetal heart rate monitor. Significant changes were detected in baseline fetal heart rate (P less than 0.005), heart rate variability (P less than 0.05), number of dips (P less than 0.01) and their depth (P less than 0.01). The results encourage confidence in the sensitivity of fetal monitoring for the detection of changes in a number of fetal heart rate variables during the course of labour. PMID- 1405563 TI - Use of hot wire anemometry to measure velocity of the limb during human movement. AB - Hot film anemometry, x-configuration probes were used in two experiments to evaluate their effectiveness at measurement of limb velocity. Data from tests with a probe attached to the end of a pendulum establish that the hot films measure velocity in the swing phase within 0.098 ms-1. The kinetic energy per unit mass of the pendulum was predicted within +/- 0.005 m2 s-2, from the measured velocity. In gait experiments with one human subject at speeds greater than 0.25 ms-1, the hot film anemometer and a video system predicted speeds within 0.083 ms-1. The hot film data are electronic signals that are easily stored and processed. The results from these experiments demonstrate that hot film anemometry is an effective and efficient method for direct measurement and analysis of the limb velocity. PMID- 1405564 TI - Technique for the application of physiological loading to soft tissue in vitro. PMID- 1405565 TI - Monitoring movement: an electronic event counter. PMID- 1405566 TI - Comment on: bending and fracture of the femoral component in cemented total hip replacement. PMID- 1405567 TI - Influence of metabolic, mechanical and physique variables on middle distance running. AB - The purpose of this study was to determine the variables that most limit middle distance run performance e.g. 800, 1500 and 3000 meters. A predictive research design was employed as 56 runners ran each of the three distances and were evaluated for VO2max, running mechanics, physique variables, ventilatory threshold, and anaerobic capacity and power. The data were analyzed by correlation procedures and stepwise regression analysis. The variables that most limited 1500 and 3000 meter (m) run performance were identical. Maximal oxygen uptake was the most important, but stride length and anaerobic capacity and power also contributed significantly. Run performance at 800 m was influenced by a considerably different set of variables. Peak velocity was most important, but VO2max, % fat and thigh length also contributed significantly. These data indicate that 1500 and 3000 m runners can compete favorably at either distance, while 800 m runners have a different profile and would experience difficulty competing at 1500 and 3000 meters. PMID- 1405568 TI - Effect of high velocity resistance training on peak torque, cross sectional area and myofibrillar ATPase activity. AB - The purpose of this investigation was to determine the effect of high velocity resistance (HVR) training on peak torque (PT), cross sectional area (CSA) and myofibrillar ATPase activity of the knee extensors. HVR training was performed in a circuit on hydraulic exercise equipment, 4 times a week for 5 weeks at an angular velocity of approximately 3.14 rad.s-1. Knee extension PT was determined on a Cybex II isokinetic dynamometer and CSA of the quadriceps femoris muscle was assessed using computer tomography (CT) scanning. Muscle biopsies were obtained from the lateral quadriceps muscle and were analyzed for myofibrillar ATPase activity. Knee extension peak torque was significantly increased at 1.57, 2.09, 3.14, 3.66 and 4.19 rad.s-1. Myofibrillar ATPase activity and CSA was also significantly increased after HVR training. These findings showed that short-term high velocity resistance training enhances the in vivo torque/velocity curve especially at fast angular velocities and these changes are partly attributed to an increase in muscle CSA and activity of myofibrillar ATPase. PMID- 1405569 TI - Sports-related epiphyseal injuries of the lower extremity. An epidemiologic study. AB - Sports-related epiphyseal injuries in children and adolescents have been becoming more prevalent during recent years. We report 85 patients with epiphyseal fractures of the lower extremity treated in our hospital during the last twenty years, of which 60 were males and 25 females with an average age of 12.6 years (range 4 to 17 years of age). The injuries were sustained during soccer in 28% and during alpine skiing in 26% of the cases, of which the former was responsible for most of the injuries reported in males and the latter for those in females. The most frequently seen localizations were in the distal tibial epiphysis (31 cases), followed by the distal fibula (17) and the proximal tibial epiphysis (15). Of the reported 85 epiphyseal fractures 30 were Salter-Harris type I injuries, 25 type II, 8 type III and 11 were type IV fractures, while 11 were avulsion fractures. Of these patients, 56% were treated surgically, while conservative treatment was chosen for 44% of the patients. Of the 49 patients available for follow-up, complications were documented in 9 instances, including 3 leg length discrepancies, 4 axis deviations, one avascular necrosis of the femoral head and one case of osteomyelitis, of which 6 required corrective surgery. PMID- 1405570 TI - Strength training via high frequency electrical stimulation. AB - Twelve males and twelve females received 18 sessions of high frequency (2500 Hz) electrical stimulation of either the biceps brachii or triceps brachii muscles. Each session consisted of ten 10-second contractions separated by 50 seconds of rest. Pre- and post-test measurements included arm flexion and extension strength, endurance, girths and fatfolds. The analysis of variance revealed that there were no significant differences for any of the pre versus post parameters. These findings suggest that electrical stimulation, by itself, is not an adequate training stimulus in normal healthy muscles. The data support the contention that volitional training is required to gain strength. PMID- 1405571 TI - Effects of speed training on the fibre composition of the longissimus lumbaris muscle. AB - Thirty-six adult male and female Wistar rats were divided into three groups, each of which underwent different training programmes in which greater relevance was attached to the intensity of exercise than to its duration. Samples of the longissimus lumbaris muscle taken between the second and fourth lumbar vertebra, were stained with m-ATPase after acid preincubation at pH 4.4, and with NADH-TR. The most notable results obtained were: (a) none of the training programmes involved gave rise to changes in the ratio of type I: type II fibres; (b) the proportion of IIA fibres increased in all cases, while the proportion of IIB fibres decreased correspondingly; (c) the percentage of FT fibres decreased significantly, and in greater proportion than the decrease recorded in IIb fibres, and (d) specific speed training schedules led to greater changes in the fibre composition of this muscle. PMID- 1405572 TI - Blood lactate, glycerol and catecholamine in arm strokes, leg kicks and whole crawl strokes. AB - Lactate, glycerol, and catecholamine in the venous blood were determined in 8 recreational swimmers following 60 sec of supramaximal arm strokes, kicks and the whole swim. The mean velocity of a whole stroke was higher than both arm strokes and kicks, and the mean velocity of arm strokes was higher when compared with kicks. There was a significant relationship between the mean velocity of arm strokes and the whole swim (r = 0.90; p less than 0.01). Peak blood lactate in the whole swim was higher than arm strokes (p less than 0.01) and kicks (p less than 0.01), and peak blood lactate in arm strokes was higher compared to kicks (p less than 0.01). The correlation coefficients between mean velocity and peak blood lactate in arm strokes, legs kick and whole swim were r = 0.72 (p less than 0.05); r = 0.61 (n.s.) and r = 0.35 (n.s.), respectively. These results suggest (1) that lactate in the blood during the whole crawl stroke originates predominantly from the muscle groups which work the arm and (2) that glycogen included in the muscles of the upper body which is used during arm strokes was easily convertible into the propelling force during arm swim, while additional energy from the leg muscles is not fully sufficient to increase propulsion force in a linear manner. PMID- 1405573 TI - Respiratory muscle fatigue does not limit exercise performance during moderate endurance run. AB - The role of respiratory muscle fatigue in limiting exercise performance in well trained subjects is still controversial, especially as far as relatively short runs are concerned. To determine the occurrence of respiratory muscle impairment, we studied six well-trained athletes before, during (middle of the run) and after a 17 km run. They were all asked to produce the maximum effort they could during the race. Strength was assessed by measuring maximal inspiratory mouth pressure against close airways (MIP), dynamic lung volumes were monitored using a spirometer. No changes in forced vital capacity (FVC), maximal expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1) were observed throughout the experiment. This suggested that functional residual capacity and subsequently the initial length of respiratory muscle were unchanged. Respiratory muscle strength did not significantly vary at the different time of measurements (154.8 +/- 20.9 cm H2O at the beginning, 157.5 +/- 23.7 cm H2O after 7.5 km, 155.8 +/- 22.5 cm H2O at the end and 152.3 +/- 17.6 cm H2O after 30 min of recovery). We therefore conclude that respiratory muscle fatigue does not impair the exercise performance of well-trained athletes in a relatively short race. The difference between these results and others reported in literature, could be explained by the different degree of training of the subjects performing the race. PMID- 1405574 TI - Characteristics of the morphological and functional status of kayakers and canoeists. AB - A study of anthropometric and functional characteristics was conducted in a sample of 29 athletes, flatwater racers 18 kayakers and 11 canoeists. The results of morphological tests suggest an evident reduction of subcutaneous fat, above average values of limb circumferences (especially upper limbs) and of body mass, attributable to a high proportion of lean body mass. Trunk extension strength was to be below the average, while the strength of the remaining analyzed static movements were on the level of trained persons. Aerobic capacity, i.e. the functioning of the cardiopulmonary system, in the sample under discussion has shown above-average values, comparable to those obtained in athletes in the aerobic sports group. The results of discriminant analysis applied separately to morphological, dynamogenic and aerobic characteristics with the aim to identify possible differences between the two sports suggest that our sample constituted a homogeneous group, regardless of which of the two sports were practiced. PMID- 1405575 TI - Diet, hormonal, and metabolic factors affecting bone mineral density in adolescent amenorrheic and eumenorrheic female runners. AB - Seven adolescent female runners with secondary amenorrhea and six adolescent eumenorrheic female runners received dietary supplements of 1200 mg calcium carbonate and 400 IU vitamin D/d for 12 months. Bone mineral density (BMD) of the axial skeleton was measured by dual photon densitometry at the beginning and end of the 12 month period. Plasma estradiol and ionized calcium concentration were also determined. Bone mineral density decreased in two of the amenorrheic subjects, with the lowest estradiol values concurrent with the severest training regimen and highest calcium intake. There was a significant decrease in plasma estradiol concentration in the amenorrheic runners (p less than 0.05). Plasma ionized calcium and estradiol explained 99% of the variation in BMD (r2 = 0.999). A significant inverse relationship between plasma estradiol and miles run/week was observed (r2 = -0.748). Adolescent female runners who train extensively and have low plasma estradiol levels may be adversely affecting BMD despite supplemental calcium and vitamin D intake. PMID- 1405576 TI - Effect of treadmill exercise intensity on hepatic glutathione content and its relevance to mammary tumorigenesis. AB - These experiments assessed the role that exercise-induced alterations in glutathione metabolism might play in the acceleration of breast cancer development in rats subjected to nonexhaustive levels of treadmill running. The influence of intensity and duration of treadmill exercise on total and oxidized levels of liver glutathione was evaluated. Nonexhaustive exercise failed to alter the hepatic concentration of total glutathione. However, increasing exercise intensity resulted in tissue accumulation of oxidized glutathione, and an increase in the ratio of oxidized to total glutathione, indicative of an elevated level of intracellular oxidation. Although alterations in glutathione metabolism do not appear to be directly related to the effect of exercise on tumorigenesis, the role of oxidant-induced intracellular damage in this process is being investigated. PMID- 1405577 TI - The effects of cycling and marathon training on eighteen blood parameters. AB - Abnormal blood chemistry values may be normal for competitive cycling and marathon training, with significant differences (p less than 0.05) between the two groups. The purpose of this study was to examine the effects of bicycle training and marathon training on fasting blood chemistry values. Ten significant differences (p less than 0.05) were observed between cyclists and marathoners on the eighteen blood parameters studied, with four of the blood parameters being outside the established laboratory norms of +/- 2 standard deviations. This was shown by the elevations in creatine phosphokinase levels in the competitive cyclists with the marathoners having higher than the normal ranges for lactate dehydrogenase and lower than normal ranges for hematocrit and red blood cells. Significant differences for albumin, cholesterol, creatine phosphokinase, globulin, hematocrit, lactate dehydrogenase, low density lipoprotein, total protein, red blood cells and triglycerides were observed between the groups. PMID- 1405578 TI - Hematological status in a group of male athletes of different sports. AB - Suboptimal hematological status has been often recorded in athletes involved in intense physical activity, particularly in middle and long distance runners. It appeared therefore interesting the study and comparison of athletes groups of different sports. One hundred eighty-one male athletes were tested and divided into seven groups according to sport exercise: cross-country skiing, cycling, fencing and tennis (joined together), rowing, running, soccer, swimming. For every athletes erythrocyte and hemoglobin blood concentration, hematocrit, serum iron, transferrin, ferritin and haptoglobin concentration were measured, the mean cell volume and serum iron/transferrin ratio were calculated. Data were compared to find out correlation indices and then grouped according to the practised sport. Statistical indices were computed for each group and for all parameter and analysis of variance was carried out to value the significativity of found differences. The only parameter showing statistically significant differences among groups was the serum level of haptoglobin, with mean value significantly lower in runners. The evidence of this study suggests that individual variability for the remaining parameters exceeds any variation possibly induced by different sport practices. PMID- 1405579 TI - Acute effect of consumption/omission of breakfast on exercise tolerance in adolescents. AB - The purpose of this study was to determine the acute effects of the consumption or omission of breakfast on exercise tolerance in adolescents. Physically active adolescents (14 males and 21 females) were randomly assigned to receive a breakfast (B) or placebo (P) after an overnight fast. Exercise tolerance tests were done 1.5 hours (test 1) and again 4 hours (test 2) after consuming B or P and consisted of cycling on a stationary bike for 4 minutes at each of four consecutive power settings: 25, 50, 75, and 100 watts. Blood glucose and beta hydroxybutyrate concentrations were measured before both tests. VO2 and VCO2 were measured during minute 3 of cycling at loads 50 and 75 watts and were used to compute the respiratory exchange ratio (RER). Heart rates (HR) were monitored throughout the test and ratings of perceived exertion (RPE) were made at the end of each 4 min interval. Repeated measures ANOVA revealed that there were no differences in RPE; however, differences for HR and RER did exist. Mean RER values were higher for the males receiving B vs males receiving P during test 1. For females, HR were higher for P compared B, and beta-hydroxybutyrate was significantly elevated for P before test 2. The data suggest that exercise tolerance as indicated by the ratings of perceived exertion are unaffected by prior ingestion of a breakfast but breakfast does affect the physiologic responses to exercise. PMID- 1405580 TI - Characteristics of women performing strength training: comparison of participants and dropouts. AB - The physiological, anthropometric, personality and lifestyle characteristics of 122 women volunteering for a seven-week program of heavy resistance weight training were studied relative to adherence rates. Initially, volunteers were above-average in body mass and grip strength, but were below-average in chest girth and bicristal diameter. They were also physically active and only 20% smoked. Regular (R) attenders (attendance greater than 80%; 72% of the sample) were physically smaller in terms of stature, mass, girths and dimensions, but had greater strength per kg of mass or LBM compared to participants classified as infrequent (I; 24-76%) and dropout (DO; less than 20%). Conversely, I and DO members were more likely to smoke, to smoke more heavily, to drink coffee and to not eat breakfast. Most dropouts quit during the first week; among volunteers who continued, differences in assigned training intensity had no effect on adherence. Adherence was also unrelated to strength gains, anthropometric adaptations, or injury. PMID- 1405582 TI - The effects of positive expiratory pressure on peritoneovenous shunt flow. AB - Cirrhotic patients with peritoneovenous shunts may require mechanical ventilation. Despite the importance of flow to shunt patency and the relevance of intrathoracic pressure to that flow, the relationship between shunt flow and positive airway pressure has not been documented. To study the effects of positive expiratory pressure (PEEP) on shunt flow, models of ascites (n = 8) were created in adult male mongrel dogs. Each animal was anesthetized, intubated, and mechanically ventilated. Peritoneovenous shunts with in-line electromagnetic flow meters were surgically placed. Shunt flow, central venous pressure (CVP), and intraabdominal pressure (IAP) were monitored. Initial intraabdominal pressures were adjusted by infusion of warmed saline and positive expiratory airway pressures were added in increments. Changes in pressures (IAP, CVP) and shunt flow were tabulated and analyzed with linear and polynomial regression. Intraabdominal and central venous pressures increased linearly with PEEP at different rates such that IAP-CVP varied inversely with PEEP. Shunt flow varied inversely as a polynomial function of PEEP. Analyses of these relationships allowed creation of a nomogram which can be interpolated to indicate required intraabdominal pressure needed to maintain shunt flow throughout the clinically useful range of positive airway pressure. PMID- 1405581 TI - Does cigarette smoking affect the fitness of young adults? Rationale and protocol for future research. AB - While there is considerable evidence of the direct effects of cigarette smoking upon the cardiovascular and respiratory systems, one result of impaired function, that is how cigarette smoking affects fitness and athletic performance, has not been well documented. Because of the potential impact that exercise might have as a substitute for smoking, it is important to delineate relationships, particularly for those who are just beginning to smoke. Literature is presented as a rationale for research in this area and results of a pilot study on smokers and non-smokers are reported. A number of trends in the fitness and pulmonary function tests emerged, suggesting this line of research be pursued. PMID- 1405583 TI - Neutrophil-endothelial cell binding in neutrophil-mediated tissue injury. PMID- 1405584 TI - A cost-effective peripheral venous port system placed at the bedside. AB - High costs and a paucity of available operating time have led us to seek alternatives to operatively placed vascular access systems. This prospective study is the initial report of a peripheral port system (P.A.S. PORT System, Pharmacia Deltec, Inc.) placed at the bedside. Seventy-nine patients (52 male, 27 female), ages 3-92 years, had ports implanted by surgical residents with attending supervision. Sixty-eight (86%) received the P.A.S. PORT for long-term antibiotics, antifungal, or antiviral therapy; four (5%) for TPN infusion; three (4%) for blood products; two (3%) for chemotherapy; and two (3%) for iv narcotics. Ports were placed in 10 (13%) HIV(+) patients, three (4%) who were fully anticoagulated, and one who was a hemophiliac with a platelet count of zero. Eight patients (10%) developed superficial phlebitis, all of which resolved with nonsteroidal anti-inflammatory agents within 48 hr without port removal. Seven patients (9%) had their port removed due to infection. The average hospital charge to place the P.A.S. PORT System was $1488.00 vs $2811.00 for a tunneled external chest catheter and $3729.00 for the placement of a chest port. Bedside insertion of vascular access devices can be safely performed with acceptable infection rates allowing more efficient use of hospital operating rooms and with substantial cost savings. PMID- 1405585 TI - How rapidly do hyperinsulinaemia and hyperglucagonaemia develop after portacaval shunting? AB - Elevation of serum insulin and plasma glucagon have been reported during and immediately after clinical and experimental liver transplantation and in patients with cirrhosis and surgically created or spontaneous portacaval shunts. There is controversy about the relative roles of portal diversion and impaired liver function in the genesis of these elevated levels of pancreatic hormones. End-to side portacaval shunt was made in normal pigs which were fitted with catheters which allowed transhepatic sampling during and for 4 hr after the operation. Within 5 min of opening the shunt, there was a sixfold increase in portal venous insulin concentrations but hepatic clearance of insulin and the arterial concentration were unaltered. The increase in insulin was sustained for 2 hr. A twofold increase occurred within 1 hr in portal venous glucagon concentration which appeared to be predominantly of pancreatic origin and which continued for the 4 hr of the study. Hepatic glucose uptake did not occur after portacaval shunting despite levels of glucose elevated two-fold by iv infusion. There were no changes in aspartate aminotransferase, hepatic tissue energy charge, or total adenine nucleotides, suggesting that hepatic function was intact. It is concluded that portal diversion results in an increase in insulin and glucagon secretion and in the absence of hepatic uptake of glucose. This is a novel observation with relevance especially in liver transplantation when portal diversion for at least 1 hr forms part of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405586 TI - Biochemical analysis of the venous flap in the dog. AB - There has been great interest stimulated by reports on factors influencing the survival of skin flaps which possess only venous inflow and outflow, i.e., venous flaps. The present study serially (Days 1, 2, and 4 postoperatively) observed several biochemical factors which might affect flap survival. ATP levels were measured to assess endogenous energy stores, malonyldialdehyde (MDA) and xanthine oxidase (XO) to estimate free radical production, superoxide dismutase (SOD) to quantify antioxidant defenses, and edema to measure inflammatory changes. Eighteen thighs on nine dogs were assigned randomly to one of three groups: full thickness skin grafts, flaps based solely on the saphenous artery and vein (AV flaps), or flaps based solely on the saphenous vein (venous flaps). These were regarded as being mostly ischemic, totally perfused, and partially ischemic, respectively. Control skin biopsies were obtained adjacent to surgical sites. AV flaps and control skin were similar in all respects. Venous flaps compared with skin grafts were significantly less edematous (P less than 0.01) had less MDA and XO (P less than 0.05), but no significant differences in SOD and ATP levels. However venous flaps had significantly less ATP than AV flaps (P less than 0.01). Thus venous flaps survive despite depletion of ATP levels. These results suggest that decreased free radical production and lessened edema may be important factors in promoting ultimate survival of venous flaps. PMID- 1405587 TI - Effect of local tumor removal and retained oncolysate on lung metastasis. AB - We reported earlier that oncolysate retained in the excision wound of a local tumor inhibits growth of remote tumor in the rat. We further studied this effect on pulmonary metastasis. C57BL/6 mice were given B16 melanoma F10 cells subcutaneously into the gluteal area (Day 0) and then intravenously on Day 10. On Day 14, mice were divided into four groups. Group 1 received a sham operation and no further treatment. Tumors were excised in the remaining mice. Group 2 received tumor excision alone. Groups 3 and 4 received injections of freeze-lysed tumor cells (TC) and lysate modified (PTC) with a hapten, L-phenylalanine mustard (PhM), respectively, into excision wounds. On Day 24, metastases were assessed by determining metastatic burden. Average diameters of excised tumors in repeated experiments ranged from 8.7 to 10.9 mm. In repeat experiments, pulmonary metastatic burden increased by as much as 52 to 181% in the tumor excised group (Group 2) in comparison with those receiving sham surgery (Group 1). However, metastatic burden was always reduced in Group 3. An even greater reduction was seen in Group 4. To study the possible involvement of macrophages, the production of prostaglandin-E2 (PGE2) and cytotoxicity of macrophages in these animals were examined. It was found that tumor excision enhanced PGE2 production by macrophages and suppressed their cytotoxicity, while TC inoculation prevented both of these changes. An even greater prevention was observed with PTC inoculation. These results indicate an association among macrophage cytotoxicity, PGE2 production of macrophages, and metastasis. In order to clarify the mechanism for these reactions, we did experiments using adherent splenic macrophages from the four groups of animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405588 TI - The effects of laser-assisted fibrinogen bonding on suture material. AB - To evaluate the effect of laser-assisted fibrinogen bonding on the tensile strength of suture material, 10 types of sutures were exposed to various time intervals of diode laser energy after pretreatment with dye-enhanced fibrinogen solder. After exposure, each suture material was stressed on a tensometer and compared with nonlased suture material. Our results indicate that polytetrafluoroethylene suture material was virtually unaffected at all time intervals of exposure to laser energy. Polyester suture material retained 64.3% of its tensile strength at 60 sec of exposure to laser energy. White silk suture material maintained 80% of its initial tensile strength at 60 sec of exposure. These suture materials may be used safely in conjunction with laser-assisted fibrinogen bonding even if prolonged laser exposure is necessary. The other suture materials tested may be compromised significantly by prolonged exposure to laser energy and must be used with relatively shorter irradiation periods. PMID- 1405589 TI - Results of cholescintigraphy in a VA hospital. AB - In a review of 200 hepatobiliary imaging studies done in a VA hospital over a 5 year period, a sensitivity of 96% and a specificity of 88% were obtained. In a subgroup of 40 patients with alcoholic liver disease, the specificity dropped to 60% although the sensitivity remained high (100%). These data indicated that in patients with alcoholic liver disease a positive DISIDA scan is not diagnostic of acute cholecystitis and cannot be interpreted as an indication for cholecystectomy. Possible modifications of imaging techniques, including delayed imaging and morphine-augmented cholescintigraphy, may prove to increase the specificity of cholescintigraphy in these patients. A prospective study using these modifications would help in determining the current role of cholescintigraphy in the diagnosis of acute cholecystitis in patients with alcoholic liver disease. PMID- 1405590 TI - Effect of complete cardiac denervation on atrial natriuretic factor release in baboons. AB - We investigated the influence of cardiac innervation on atrial natriuretic factor (ANF) release in baboons. For this purpose, plasma ANF levels were measured in control conditions and in response to head-down (-45 degrees) and head-up tilt (+45 degrees) in six anesthetized baboons before and after complete cardiac denervation obtained by orthotopic autotransplantation of the heart. Cardiac denervation did not modify baseline plasma ANF levels (60.4 +/- 17 pg/ml before and 63.1 +/- 16 pg/ml after heart autotransplantation). In contrast the significant ANF responses to changes in central venous pressure (CVP) induced by postural maneuvers (-45 degrees, + 16.2 +/- 4 pg/ml; +45 degrees, -18.5 +/- 4 pg/ml) were markedly altered after cardiac denervation (-45 degrees, +5.8 +/- 2 pg/ml; +45 degrees, -7.6 +/- 1 pg/ml). The changes in CVP and systemic blood pressure evoked by the postural challenges were comparable before and after cardiac denervation. These results demonstrate that cardiac nerves play a role in the control of ANF release. PMID- 1405591 TI - Epidermal growth factor accelerates connective tissue wound healing in the perforated rat mesentery. AB - Epidermal growth factor (EGF) has been reported to stimulate healing of wounds in skin, cornea, and gastric mucosa. In the present study, we further investigate the effect of endogenous and exogenous EGF in healing of connective tissue wounds using the rat perforated mesentery model. Healing of mesenteric perforations is accomplished by the connective tissue fibroblasts since there are no interfering variables such as interactions of epithelial cells, desiccation, or foreign materials such as sutures or subcutaneous implants. We performed laparotomy in 114 adult male Sprague-Dawley rats and made 20 standardized perforations in the mesentery of each rat with a scalpel. Rats were randomly assigned to five groups. Group I received no treatment after surgery; Group II received intraperitoneal injections of phosphate-buffered saline (PBS) after surgery and then twice daily for the following 3 days; Group III received 10 micrograms of EGF in the PBS injections according to the same regimen as Group II; Group IV had sham exploration of the submandibular salivary glands; and Group V animals had excision of the submandibular glands 3 days before laparotomy to deprive the main source of EGF in rat. On Days 4 through 10 after surgery rats were sacrificed and the percentage of perforations in each rat which were closed was determined. The curves for the time course of wound closure for Groups IV and V were not different indicating that endogenous submandibular EGF does not play a role in healing of mesenteric wounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405592 TI - Ibuprofen restores cellular immunity and decreases susceptibility to sepsis following hemorrhage. AB - Although hemorrhage depresses splenocyte (SPL) functions and increases susceptibility to sepsis, it is not known whether increased tumor necrosis factor (TNF) or prostaglandin (PG) production are responsible for it. To study this, mice (C3H/HeN) were bled to a mean blood pressure of 35 mm Hg, maintained at that pressure for 60 min, resuscitated, and treated with ibuprofen (1.0 mg/kg body weight) or vehicle (saline). Hemorrhage reduced (P less than 0.05) SPL proliferation by 60%, SPL release of interleukin-2 (IL-2) by 47%, interferon gamma (IFN-gamma) by 67%, TNF by 54%, and interleukin-6 (IL-6) by 46% compared to sham. In addition, splenic macrophage (sM phi) release of interleukin-1 (IL-1) and TNF was decreased by 58 and 67% (P less than 0.05), respectively. However, ibuprofen treatment increased (P less than 0.05) SPL proliferation, lymphokine (IL-2, IFN-gamma, and IL-6) synthesis, and IL-1 release by sM phi compared to hemorrhage alone. Furthermore, ibuprofen enhanced the release of TNF by SPL (+175%, P less than 0.05) and sM phi (+68%) compared to the vehicle group. Ibuprofen also decreased (P = 0.011) the susceptibility to sepsis following hemorrhage. These results indicate that PGs are involved in hemorrhage-induced suppression of cellular immunity and in the increased mortality of such animals following a septic challenge. PMID- 1405593 TI - DMSO protects against adriamycin-induced tissue necrosis. AB - Inadvertent extravasation of Adriamycin (Adria) can result in severe tissue necrosis. The mechanism of this tissue damage is believed to be the release of free radicals into the tissue. Topical applications of dimethylsulfoxide (DMSO) used after Adria extravasation have been shown to decrease ulcer size. This may be due to DMSO's ability to scavenge free radicals. However, effective topical therapy requires prompt recognition of extravasation, which is often difficult. We hypothesized that the delivery of Adria in low concentrations DMSO would reduce Adria-induced ulcer size and ulcer incidence caused by Adria extravasation. To test this hypothesis, 180, male Sprague-Dawley rats were randomly allocated into three treatment groups of 60 each. All three groups received intradermal injections of Adria (1 mg) diluted in 0.5 cc of saline (Group 1), 10% DMSO (Group 2), or 20% DMSO (Group 3). Rats were observed for 4 weeks. Ulcer incidence (%) and size of ulcers (mm2) were assessed over time. Area of skin ulceration was calculated as the product of the two greatest diameters. Statistical evaluation of the differences in incidence and ulcer size between Group 1 and Groups 2 or 3 were evaluated using analysis of variance. Delivery of Adriamycin in 10 or 20% DMSO resulted in a statistically significant (P less than 0.001) decrease in the incidence of ulceration caused by intentional Adria extravasation. PMID- 1405594 TI - Roux-en-Y jejunal bypass abolishes postprandial neuropeptide Y release. AB - Numerous physiologic aberrations occur after Roux-en-Y bypass procedures. Neuropeptide Y (NPY), a 36 amino acid polypeptide, has been shown to have many effects on gastrointestinal physiology, including alterations in blood flow, motility, and secretion and absorption. Recent work demonstrating a postprandial increase in circulating NPY prompted this investigation into its potential roles after Roux-en-Y bypass. Three groups of rats underwent Roux-en-Y cholangiojejunostomy, jejunojejunostomy, or proximal jejunal transection with reanastomosis. After a 3-month recovery, the animals were tested with both mixed and fat meals. Control animals had rapid increases in circulating NPY after the mixed meal. This response was not seen in either of the Roux-en-Y groups (P less than 0.05). No animals had circulating changes in NPY after the fat meal. Additionally, small intestinal NPY receptor analysis revealed high NPY affinity to the epithelial cells of the proximal small intestine. Our results demonstrate a dependence of postprandial NPY release on proximal small intestinal continuity that is abolished by Roux-en-Y bypass of a jejunal segment. The absence of postprandial elevation in plasma NPY after proximal jejunal bypass and the abundance of NPY receptors in the proximal small intestine merits further investigation into the physiologic roles of NPY in the foregut. PMID- 1405595 TI - Effect of glow discharge surface modification of plasma TFE vascular graft material on fibronectin and laminin retention and endothelial cell adhesion. AB - The effects of glow discharge surface modification of plasma TFE vascular graft material (plasma TFE, Atrium Medical Corp., Hollis, NH) on the binding and retention of fibronectin and laminin as well as endothelial adherence were examined. The binding of both fibronectin and laminin to plasma TFE increased as a function of protein concentration in the range of 0.02 to 200 micrograms/ml. Binding to plasma TFE was not saturable in this range of protein concentrations. Fibronectin and laminin binding to plasma TFE was time-dependent, reaching a maximal level (1.8 and 3.2 micrograms/cm2 of bound fibronectin and laminin, respectively) after 30 min (fibronectin) and 4 hr (laminin). Binding was not the result of an accumulation of unbound protein in graft interstices since graft prewetting did not alter the amount of either fibronectin or laminin associated with plasma TFE. In addition, binding was not the result of protein modification during radiolabeling, since unlabeled fibronectin and laminin could compete effectively with their iodinated counterparts for binding to plasma TFE. Dissociation of bound fibronectin and laminin from plasma TFE was rapid, and less than 12% remained bound 60 min after washing. Plasma TFE subjected to glow discharge in O2 and carrying negatively charged functional groups on graft surfaces, exhibited a fivefold increase in fibronectin and laminin binding. In addition, more than 85% of the bound fibronectin and laminin was retained 24 hr after washing. The enhanced retention of fibronectin or laminin by these grafts was associated with an increase in endothelial cell adhesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405596 TI - Hormonal control of opossum sphincter of Oddi motility: role of myoneural continuity to duodenum. AB - Motilin and caerulein are known to affect motility of the sphincter of Oddi (SO) and the gastrointestinal tract. The role of SO-duodenal myoneural continuity in the action of these peptides was studied. Five opossums had translocation of the duodenal papilla into the jejunum, while preserving the blood supply to the SO and duodenum. Serosal electrodes were placed in the SO, duodenum, and jejunum. Five control animals had electrode placement alone. Myoelectric recording was obtained during fasting and after administration of motilin (400 ng/kg) or caerulein (500 ng/kg/hr). Motilin induced premature phase III-like activity in the SO and intestine in controls. After the translocation of the papilla, the spike frequencies during phase II and phase III were significantly lower than in controls, whereas those during phase I and phase IV were not different. Motilin caused premature intestinal phase III and increased SO spike activity. However, the increase in SO spike activity was insufficient to form phase III. Caerulein produced a sustained increase in spike activity in both regions in both groups, but the increase was less in the translocation group than in controls. These data suggest that duodenal activity stimulated by motilin and caerulein participates in the activation of SO motility via intrinsic myoneural pathways. PMID- 1405597 TI - Improved distribution of antegrade cardioplegic solution with simultaneous coronary sinus occlusion following acute coronary artery occlusion. AB - This study was designed to evaluate the distribution of cardioplegic solution infused antegradely with simultaneous coronary sinus occlusion. After 1 hr LAD occlusion, sheep were placed on cardiopulmonary bypass. Hearts were arrested with 300 ml of cold cardioplegia and replenished with two additional doses. In group I (n = 10), antegrade cardioplegia (ACP) was given alone; in group II (n = 9), ACP was given in combination with simultaneous coronary sinus occlusion. Microspheres were infused into the cardioplegic line to determine the antegrade distribution of the solution, while a different microsphere was injected into the anterior interventricular vein to detect the venous backflow of the solution. The data showed that myocardium distal to LAD occlusion in group II received more antegrade (0.17 +/- 0.02 versus 0.06 +/- 0.02 ml/g/min, P less than 0.01, in subendocardium; and 0.15 +/- 0.03 versus 0.09 +/- 0.02 ml/g/min, P = NS, in subepicardium) and retrograde (2181 +/- 455 versus 0 counts/g/min, P less than 0.01, in subendocardium; and 2,146 +/- 527 versus 0 counts/g/min, P less than 0.01, in subepicardium) distribution of cardioplegic solution in comparison to group I. We therefore conclude that simultaneous coronary sinus occlusion significantly improves the distribution of antegrade cardioplegic solution to the regionally occluded myocardium by increasing collateral flow as well as venous backflow. PMID- 1405598 TI - Optimal site and amount of splenic tissue for autotransplantation. AB - Clinical and basic studies have documented a high susceptibility to pneumococcal infection in asplenic humans and animals. It has been suggested that autotransplantation of splenic tissue might be a method of providing host resistance when total splenectomy is necessary. However, the effect of splenic autograft has remained controversial. This study was performed to evaluate the most effective site and amount of splenic autograft using rats. Rats were divided into five groups for the purpose of determining the site of splenic autotransplantation: splenectomy, sham operation, implantation into the omental pouch, intraperitoneal implantation, and intramuscular implantation. For determining the amount for autotransplantation, the rats were divided into seven groups: splenectomy, sham operation, and implantations of 25, 50, 100, 200, or 300 mg of splenic tissue. All animals were challenged with Streptococcus pneumoniae type 6, 16 weeks after surgery. Howell-Jolly bodies appeared postsplenectomy, but disappeared in the implanted rats 16 weeks after the operation. Histologically, the implanted tissue was indistinguishable from that of a normal spleen. Pneumococcal clearance from the bloodstream and survival rate were significantly higher in rats implanted in the omental pouch as compared with splenectomized rats. Intraperitoneal and intramuscular implanted rats did not show a significant difference from the splenectomized rats. More than 50% of splenic tissue for autograft showed a significant increase in pneumococcal clearance and survival rate as compared with that of splenectomized rats. It was suggested that the most effective site of autotransplantation is the omental pouch and approximately 50% of the whole spleen would be necessary for prevention from sepsis. PMID- 1405599 TI - Acceleration of soft tissue repair by a thrombin-derived oligopeptide. AB - Augmentation of thrombin-modulated chemotaxis and mitogenic activity within the early phase of soft tissue repair is now possible. Identification of high affinity thrombin receptor binding domains within thrombin has enabled the synthesis of a family of peptides which interact with thrombin receptors and enhance in vitro mitogenesis. A single (5.0 micrograms/wound) application of the thrombin receptor-activating peptide (P517-30) significantly increased wound breaking strength from Day 5 (31% over controls) to Day 12. Two models of impaired healing created by radiotherapy (RT) were used to elucidate possible mechanisms of P517-30 action. Although P517-30 did not completely overcome the RT induced healing impairments, it increased breaking strength under conditions of penetrating whole body RT-induced pancytopenia by 22% and of nonpenetrating surface RT-induced dermal cell damage by 42%. This suggests that P517-30 directly stimulates resident endothelial cells, fibroblasts, or other cells to overcome dermal and circulating monocytic deficits. These results suggest a method to accelerate wound healing with potential clinical applications and emphasize the activity of thrombin as a growth factor. PMID- 1405600 TI - Lectin histochemical investigations of fetal cultivated pancreatic tissue. AB - The terminal glycoproteins of fetal, cultivated (7-12 days), and adult nondiabetic and diabetic pancreatic tissues (Balb c, C3h mice) were investigated by lectin histology (peanut-, phytohemagglutinin, wheat germ agglutinin, Ulex europeus I, concanavalin A and Ricinus communis agglutinin, PaP method +/- neuraminidase). Anti-insulin and -glucagon were used to identify islet cells. S 100 antibody showed dendritic reticulum cells, anti-IAK proved MHC II antigens (C3h). Cultured tissue was partly incubated with anti-IAK and complement for lysis of MHC II antigens. On the 19th gestational day fetal pancreatic tissue did not bind peanut agglutinin, Phytohemagglutinin, or wheat germ agglutinin, whereas concanavalin A and Ricinus communis were weakly bound. Terminal fucose residues were not expressed by C3h fetal islet cells in contrast to Balb c. Following neuraminidase digestion peanut agglutinin and phytohemagglutinin were strongly bound, indicating sialic acid-substituted terminal glycoproteins. Cultivated tissue (Day 7) bound all investigated lectins (except Ulex europeus I in C3h mice), indicating maturation of islet cells. In spite of the peak of insulin concentration in the medium we observed a faint binding of anti-insulin and investigated lectins following 12 days of cultivation. This indicates a disorder of terminal glycoprotein synthesis at this point. There was no difference in lectin binding patterns of adult nondiabetic islet cells compared to the cultivated tissue (7 days), but no Ulex europaeus I binding of the adult Balb c mice was observed. S-100 binding decreased during the cultivation period as dendritic reticulum cells became destroyed by cultivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405601 TI - Treatment of experimental liver metastases with a noncontact neodymium: YAG laser. AB - The extent of tumor and liver damage after treatment with the neodymium:yttrium aluminum-garnet (Nd:YAG) laser was investigated in a rat tumor model. Colon carcinoma CC531 was implanted in the liver and treated with 60 J (14 tumors), 120 J (15 tumors), or 180 J (12 tumors) at a power setting of 20 W. To assess the effects upon the tissues three animals were sacrificed immediately after treatment and 1, 2, 4, and 8 days later. Sections from the tumor sites were evaluated by light microscopy and the maximal depth and width of different zones of tissue damage were measured. Laser effects could be determined most accurately on Days 1 and 2 after treatment. Multiple linear regression analysis of the data indicated a linear relationship between laser energy and depth of tumor damage (P less than 0.01). The results of this study show the potential of the Nd:YAG laser to produce tumor coagulation necrosis with minimal liver necrosis. PMID- 1405602 TI - Cholecystokinin does not mediate glucose's cytoprotective effects. AB - Cold restraint stress produces acute gastric mucosal injury in association with altered gastric motility. Enteral nutrients prevent this injury in conjunction with inhibition of gastric emptying. Because cholecystokinin (CCK) is released by nutrients known to be cytoprotective and is thought to inhibit gastric emptying, we performed three experiments to see if CCK contributes to the gastric mucosal protection afforded by enteral nutrients. Our data show that enteral glucose protects the gastric mucosa and increases gastric volume, gastric luminal pH, and gastric mucin. Neither physiologic nor pharmacologic doses of CCK protected the mucosa. None of the other significant effects of glucose on gastric function during cold restraint were affected by exogenous CCK. Furthermore, antagonism of CCK receptors with L-364,718 did not have any independent effects, nor did it diminish the protection associated with enteral glucose. We conclude that enteral glucose protects the gastric mucosa from cold restraint injury in association with a number of potentially beneficial effects on gastric physiology, but none of the effects of glucose in this model appear to be mediated by CCK. PMID- 1405603 TI - Divergent effects of TNF alpha in the adoptive immunotherapy of a murine sarcoma. AB - We have previously described an in vitro sensitization (IVS) procedure which enabled the generation of therapeutic T cells from tumor-bearing mice for adoptive immunotherapy. The procedure involved culture of tumor-draining lymph node (TDLN) cells with irradiated tumor in the presence of interleukin-2 (IL-2). The availability of many recombinant cytokines affords an opportunity to examine their effects on the immune response to tumor. In this study, we investigated the effect of tumor necrosis factor-alpha (TNF alpha) on the generation and function of IVS cells utilized in adoptive immunotherapy of the murine MCA 106 sarcoma. TNF alpha administered iv at nontherapeutic doses was found to enhance the antitumor efficacy mediated by IVS cells plus IL-2 in the treatment of pulmonary metastases. In contrast, TNF alpha administration to mice bearing progressive footpad tumors had inhibitory effects on the sensitization of tumor-reactive cells in TDLN since IVS cells generated from these animals displayed a diminished antitumor effect. This effect appeared to be due to a reduced number of tumor reactive lymphoid cells in the TDLN since TNF alpha added to IVS cultures did not alter the antitumor efficacy of the resultant IVS effector cells. These findings indicate the divergent effects of TNF alpha on the immune response to tumor and adoptive immunotherapy with IVS cells. PMID- 1405604 TI - An improved technique for isolated perfusion of rat livers and an evaluation of perfusates. AB - We have modified the apparatus for isolated rat liver perfusion (IPRL) in order to be able to perform two perfusions simultaneously. In addition, we studied the quality and stability of livers by comparison of five different perfusates: Blood (Group A), Original Krebs Henseleit buffer (Group B), Krebs buffer with glucose (Group C) or bovine serum albumin (BSA) added, (Group D). In a last group (E) albumin, glucose, and taurocholic acid were added to Krebs. After 180 min of perfusion, livers perfused with solutions including 2% albumin (Group D, E) had a significantly higher release of hepatocellular and endothelial cell (purine nucleoside phosphorylase) enzymes and lower bile production as compared to Groups A, B, and C (P less than 0.0001). Increasing levels of purine nucleoside phosphorylase (PNP), a reflection of damage to the microvascular endothelium preceded the increases in hepatocellular enzymes. Histologically, damages of sinusoidal endothelial cells and hepatocytes are appreciated moderate to severe in Groups D and E, slight to mild in Groups A and B, and not significant in Group C. These results suggest that BSA may have toxic effects to the perfused rat liver. These data also confirm that the IPRL modified for simultaneous perfusion of two livers is efficient, and that with this technique the rat liver can be optimally perfused for up to 3 hr with oxygenated Krebs Henseleit buffer without additives (Group B) and without blood. These two improvements should allow those performing studies with perfused rat livers to obtain data in a more efficient, accurate, and inexpensive fashion. PMID- 1405605 TI - Lipopolysaccharide-induced stimulation of alveolar macrophage opsonin-independent phagocytosis. AB - Alveolar macrophage (AM) opsonin-independent phagocytosis may be an important process by which bacteria are cleared from the airspaces. Although it has been shown that clearance of bacteria from the lung is altered in association with endotoxemia, the effect of endotoxemia on opsonin-independent phagocytosis is unknown. Because alterations in AM opsonin-independent phagocytosis could potentially influence bacterial clearance in the lung, we studied the effects of the intravenous injection of Escherichia coli lipopolysaccharide (LPS) into rats on AM opsonin-independent phagocytosis of latex particles. AM obtained by bronchoalveolar lavage (BAL) 2 or 4 hr after injection of LPS demonstrated phagocytosis comparable to AM from control animals. In contrast, AM obtained 12 hr after injection of LPS demonstrated a nearly threefold increase in phagocytosis. Depletion of serum complement with Naja naja cobra venom factor (CVF) did not alter LPS-induced augmentation of phagocytosis. Furthermore, phagocytosis of AM obtained by BAL 2 or 12 hr after activation of complement by injection of CVF was not significantly different from that of AM from control animals, indicating that complement activation alone was not sufficient to stimulate opsonin-independent phagocytosis. These observations suggest that opsonin-independent phagocytosis may represent an important route of bacterial uptake by AM following endotoxemia, and that LPS-induced stimulation of AM opsonin-independent phagocytosis may occur independently of activation of complement by LPS. PMID- 1405606 TI - Small intestinal submucosa as a superior vena cava graft in the dog. AB - Autogenous spiral vein grafts and ePTFE have been used for reconstruction of the superior vena cava with moderate success. We tested autogenous small intestine submucosa as a superior vena cava interpositional graft in nine dogs. All dogs received aspirin and warfarin sodium for the first 8 weeks after surgery. Graft patency was evaluated by serial venography. One dog died from excessive anticoagulation. Eight dogs were sacrificed at periodic intervals until 72 weeks after surgery. Patent grafts had no evidence of thrombosis, aneurysm, or stenosis. The grafts consisted of dense, organized collagenous connective tissue with a complete endothelial cell layer on the luminal surface. Two dogs are alive at 28 and 34 months after surgery. Graft patency was 89% (eight of nine grafts). We conclude that autogenous small intestine submucosa can be used as a superior vena cava graft in the dog and is worthy of further investigations. PMID- 1405607 TI - Pretransplant sensitization with major histocompatibility complex class I+ class II- hepatocytes leads to accelerated skin graft rejection. AB - The immunogenicity of major histocompatibility complex (MHC) class I+ class II- hepatocytes is controversial. We studied the effect of pretransplant donor specific sensitization with either purified hepatocytes (HC) or splenocytes (Spl) on subsequent skin allograft survival. Five million Percoll-purified DBA HC or 10 x 10(6) DBA Spl were injected into C57BL/6 recipients either intraperitoneally (ip) or into a sponge matrix allograft. Twelve days later, sensitized mice received a DBA skin graft. On the same day, allogeneic (DBA) and syngeneic (BL/6) skin grafts were placed on naive BL/6 mice. In naive BL/6 mice, allogeneic skin graft survival was 7.8 +/- 0.5 days (n = 4), and syngeneic survival was indefinite (n = 5). Skin graft survival (mean +/- SD in days) in recipients sensitized with hepatocytes ip was 6.0 +/- 1.2 days (n = 5) compared with 5.6 +/- 0.5 days in recipients sensitized with splenocytes ip. Similarly, graft survival in recipients that received hepatocytes into a sponge matrix allograft was 5.67 +/- 1 days (n = 6) compared with 5.2 +/- 1.1 days (n = 8) in those that received splenocytes into the sponge. There was no difference in graft survival between mice sensitized with HC vs Spl, nor between mice injected ip vs with the sponge. All sensitized mice experienced accelerated graft rejection compared with naive controls (P less than 0.000). These results demonstrate that purified MHC class I+, class II- murine HCs are immunogenic in vivo. Sensitization with donor specific HCs led to accelerated rejection of subsequent skin grafts, similar to the accelerated rejection seen after sensitization with MHC class I+ and class II+ splenocytes. PMID- 1405608 TI - Identification of a novel cell population in nonhealing wounds in tumors. AB - We have explored wound healing in tumors as a possible model for tumor-host interaction. This work demonstrated tumor wound healing failure to be the result of intense inhibition of fibroblasts although the tumor cells did not appear to be the direct source of the inhibitors. The inflammatory infiltrate found in tumor wounds was then examined for possible sources of the observed fibroblast suppression. Although the tumor wound infiltrate contains cell populations similar to a normal wound infiltrate, it also contains a large, vacuolated, nonadherent, phagocytic mononuclear cell which has morphologic and cytochemical characteristics of a lipid-laden macrophage. However, the cell also proliferates under normal culture conditions and has an immunophenotype more characteristic of lymphocytes than those of macrophages with striking expression of the CD8 surface antigen. Conditioned media from this cell population markedly inhibit fibroblast proliferation suggesting it is the source of fibroblast inhibitors within the tumor wound. Mechanical dissociation of non-wounded tumors yielded evidence that the tumor wound cell is normally present in small numbers within the tumor. PMID- 1405609 TI - Suramin interference with transforming growth factor-beta inhibition of human renal cell carcinoma in culture. AB - Suramin is a polyanionic compound used clinically for the treatment of trypanosomiasis, which is known to inhibit the action of many protein factors in vitro. Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory protein which inhibits the growth of renal cell carcinoma in culture. While suramin at 50-500 micrograms/ml had no significant effect on the growth of renal cell carcinoma in culture in our experiments, it did partially reverse the growth inhibition induced by TGF-beta in the two cell lines tested. This effect apparently is caused by suramin's direct interference with 125I-labeled TGF beta's ability to bind to the cell, and not by any effect of suramin on the TGF beta receptor. Furthermore, suramin dissociates TGF-beta bound to the cell with a t1/2 of less than 30 min. These results are consistent with those previously reported regarding suramin's interaction with other protein growth factors, and suggest that suramin may interact with the TGF-beta protein itself to inactivate it. PMID- 1405610 TI - Intratumoral rIL2-based immunotherapy in B16 melanoma. AB - Limiting factors in systemic recombinant interleukin-2 (rIL2) therapy may be overcome by intratumoral (IT) administration. A series of experiments was conducted to assess the efficacy of IT rIL2 alone and in combination with LAK cells and IFN-gamma. C57BL/6 mice bearing B16-F10 subcutaneous tumors were randomly assigned to treatment groups including: noninjected controls, IT placebo (NaCl, D5W), IT bovine serum albumin (BSA), IT rIL2 (centrally and peripherally), IT rIL2/LAK, IT rIL2/IFN-gamma, and intraperitoneal (IP) rIL2. A tumor size dependent dose of cytokine was injected daily and LAK cells were given weekly. Systemic immune response was assessed by splenocyte mitogenesis and T-cell subset distribution using thymidine radioassay and flow cytometry, respectively. In terms of survival and tumor growth rate, IT rIL2 was superior to noninjected control, IT placebo, IT BSA, and IP rIL2 (P less than 0.05). The addition of IT LAK cells conferred no therapeutic advantage. The combination of rIL2 and gamma IFN-gamma had a slight survival benefit over rIL2 alone (30.8 days vs 20.4 days). Histologic analysis demonstrated an increase presence of intratumoral macrophages in the IT rIL2-treated tumors (P less than 0.05). Lymphocyte mitogenesis and L3T4+ subset were not altered by any treatment. In vitro thymidine uptake by tumor cells was not affected by rIL2 nor IFN-gamma alone but the combination of rIL2 and IFN-gamma resulted in significant tumor cell growth inhibition. Spontaneous lung metastases were more prevalent following central IT rIL2 (75% vs 29%, P = 0.07) not accountable by needle trauma but avoidable by the use of peritumoral injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405611 TI - Contrast-induced nephrotoxicity: the effects of vasodilator therapy. AB - The increasingly frequent use of contrast-enhanced imaging for diagnosis or intervention in patients with peripheral vascular disease has generated concern about the incidence and avoidance of contrast-induced nephrotoxicity (CIN). In this prospective study, we sought to identify those patients at greater risk of developing CIN and to evaluate the efficacy of vasodilator therapy with dopamine in limiting this complication. Baseline serum creatinine (Cr) concentrations were obtained on admission and daily for up to 72 hr after angiography in 222 patients undergoing 232 angiographic procedures. The preangiographic treatment was varied at 2-month intervals for 1 year. All patients received an intravenous infusion of 5% dextrose and 0.45% normal saline at a rate of 75 to 125 ml/hr. During the first interval patients received 12.5 g of 25% mannitol immediately prior to their contrast load, in addition to intravenous fluids. During the next 2-month period the patients were given renal dose dopamine intravenously (3 micrograms/kg/min) commencing the evening before angiography and continued to the next morning. During the latter half of the study the treatment regimens were modified so that the use of mannitol was restricted to patients with diabetes mellitus and dopamine to patients with serum creatinine concentrations of > or = 2 mg/dl. Postangiographic elevation in Cr occurred in 2, 10.4, and 62% of studies in patients with baseline creatinine levels of < or = 1.2 mg/dl, 1.3 to 1.9 mg/dl, and > or = 2.0 mg/dl, respectively. None of the patients receiving dopamine experienced an elevation in creatinine. There was no statistical correlation between age, diabetes, or medication with calcium channel blockers and CIN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405612 TI - Problem-based learning: an effective educational method for a surgery clerkship. AB - Problem-based learning (PBL) has been implemented during the clinical years in a few medical schools. The purpose of this study is to determine whether PBL provides a better education than traditional methods. Students in the first and third rotations (n = 42) went through the traditional clerkship, which utilized Socratic teaching (SI), while students in the second and fourth rotations (n = 36) were taught by the PBL method. Two performance measures were used to assess clerkship effectiveness. One was a modified essay examination (MEE) administered as part of the departmental evaluation. The other was the NBME-II exam and its surgery subsection NBME-II-S. The MEE was designed to measure six dimensions of the problem-solving process. The NBME-II was utilized to measure knowledge. Unpaired t tests were used to identify statistically significant group differences. The PBL group performed significantly better on two MEE dimensions: (1) differential diagnosis formation (PBL, 92.5 +/- 0.8; SI, 89.1 +/- 0.5; P < 0.01) and (2) interpretation of clinical data (PBL, 93.3 +/- 0.6; SI, 91.6 +/- 0.4; P < 0.03). A third dimension, ordering appropriate lab and diagnostic studies, approached significance (P = 0.057), and the PBL group performed better. On the NBME-II there was not a significant difference between the two groups. However, the trend (P = 0.059) was for the PBL group to score higher on the NBME II-S (PBL mean: 502 +/- 15; SI mean: 468 +/- 12). When overall achievement was controlled for, the PBL group performed significantly better than the SI group (P = 0.046) on the NBME-II-S.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405613 TI - Isolation and characterization of rabbit cardiac endothelial cells: response to cyclic strain and growth factors in vitro. AB - Studies of the cardiac endothelium have been complicated by difficulties in isolating and maintaining cardiac endothelial cells (EC) in culture. We present in this paper a method of obtaining pure EC from rabbit hearts by collagenase digestion and membrane filtration. Pure cultures of EC displaying characteristic EC morphology, uptake of di-I-acetylated LDL, and contact-inhibition of growth were successfully maintained in culture for several weeks in media supplemented with fetal bovine serum, bovine retina-derived growth factor (RDGF), and antibiotics. Since EC in vivo are exposed to a complex pattern of physical forces we also sought to determine the proliferative response of cardiac EC subjected to pulsatile strain in vitro and compared it with the response to the addition of an exogenous growth factor, RDGF. The results demonstrate that a regimen of 60 cycles per minute, 24% cyclic strain induced a significant increase in cardiac EC proliferation and suggests that physical forces may have a trophic effect on EC proliferation. PMID- 1405614 TI - Gut feeding and hepatic hemodynamics during PEEP ventilation for acute lung injury. AB - Mechanical ventilation with positive end-expiratory pressure (PEEP) limits hepatic blood flow (HBF) and oxygen delivery (HO2D). Early gut feeding may augment hepatic hemodynamics and avoid relative ischemia in this flow-limited environment. To examine these effects, canines were instrumented with arterial, pulmonary artery, portal, and hepatic vein catheters. Splenectomy and gastrostomy were performed and the hepatic artery and portal vein were encircled with flow probes. All animals underwent lung injury with oleic acid (0.08 ml/kg) followed by the addition of 10 cm H2O PEEP to correct shunt. One group (fed) was then given a bolus elemental feeding (1 kcal/ml, 10 ml/kg) and the Control group, sterile water. Cardiac index (CI), HBF, hepatic oxygen delivery (HO2D), and hepatic oxygen consumption (HO2C) were measured at baseline (T0), after PEEP (T1), and 1 (T2) and 2 hr (T3) after feeding. Data were tested for significant changes between time points in the same group by ANOVA and significant differences were subjected to t testing. PEEP significantly decreased CI, HBF, and HO2D compared to baseline. Subsequently, gut feeding increased HBF to baseline levels and improved HO2D. HO2C also increased but hepatic O2 extraction was unchanged. There was little change noted in the control group over this same period. We conclude that gut feeding augments HBF and HO2D in this flow-limited state and may preserve splanchnic integrity in critical illness. PMID- 1405615 TI - Amino acid substrate preloading and postischemic myocardial recovery. AB - During induced myocardial ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is inhibited as anaerobic pathways predominate. Even following reperfusion, stunned myocardium uses oxygen and substrate inefficiently leading to poor functional recovery as less mechanical work is developed per oxygen utilized. Amino acids potentially can act as cardiac metabolic substrates during and after ischemia, utilizing the transamination of amino acids by the malate-aspartate shuttle to form high energy phosphates via the tricarboxylic acid cycle. We investigated if "preloading" hearts with a physiologic spectrum of amino acids could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were "preloaded" with a 0.05% amino acid perfusion for 30 min prior to cardioplegic ischemia. Following reperfusion, analysis of functional recovery revealed that contractility and cardiac efficiency were improved with amino acids substrate preloading. The mechanism of this may be due to uptake of amino acids prior to ischemia, which are later utilized for internal reparative work during ischemia and external contractile work after ischemia. PMID- 1405616 TI - Diphenylhydantoin inhibits calcification of bovine pericardial implants and myocardium: a preliminary study. AB - Calcification is a major cause of glutaraldehyde-fixed bioprosthetic valve failure. Recent studies have shown that dystrophic calcification shares basic features with normal bone mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. In this study, we observed that calcification of the myocardium of DBA/2J mice was inhibited or reversed by diets supplemented with 100 mg/kg diet diphenylhydantoin (dilantin) for 70 days, with a calcification incidence of 25% in the dilantin group versus 58% in control. We further studied the effects of dilantin on bioprosthetic valve calcification. Three groups of young male Sprague Dawley rats (100 g, 9/group) were implanted subcutaneously with 1-cm2 pieces of glutaraldehyde-fixed bovine pericardium. Controls were fed a ground chow for 45 or 90 days postimplantation; experimentals received the same chow for the first 45 days postimplantation and then were fed the same diet supplemented with 1000 mg dilantin/kg for the succeeding 45 days. Calcium content (microgram/mg dry weight) of the implants in the dilantin group was 137 +/- 18.6 versus 214 +/- 34.3 in 90 days control and 79.9 +/- 41.5 in 45 days control (mean +/- SD, P < 0.01 and P < 0.05 respectively, t test). The tibia calcium content of the dilantin group was not significantly different from 90 days control. We conclude that orally administered dilantin inhibits calcification of glutaraldehyde-fixed bovine pericardial implants preferentially. It does not cause decalcification either of implants that have already calcified or of the bones. The anti calcification effect of dilantin may be associated with its anti-vitamin D effect. PMID- 1405617 TI - Fibrinolytic drugs prevent pericardial adhesions in the rabbit. AB - Epicardial adhesions are believed to form secondarily to impaired pericardial fibrinolytic activity. This activity was reconstituted in a rabbit pericardial adhesion model with single doses of the fibrinolytic agents tissue plasminogen activator (t-PA), t-PA analog (Fb-Fb-CF), and streptokinase (SK), resulting in reductions in the extent and tenacity of adhesion formation. Adhesions of the median strip of the anterior cardiac surface were reduced in area from 89% (n = 22) in controls, to 28% (n = 5) by treatment with Fb-Fb-CF (0.94 mg), and to 49% (n = 7) by treatment with SK (93,750 IU). A modified fabric of oxidized regenerated cellulose (mTC7) used to deliver the agent to the cardiac surface did not interfere with the activity of these agents (Fb-Fb-CF 19%, n = 14; SK 33%, n = 7). t-PA (0.94 mg) was also found to reduce adhesion formation in combination with mTC7 (4%, n = 4), although the appearance of significant postoperative bruising and bleeding resulted in a decision to terminate the treatment of further animals with t-PA with and without mTC7. Postoperative bruising, bleeding, and swelling, to a lesser extent, were associated with SK and Fb-Fb-CF. Despite the efficacy of the these fibrinolytic drugs further work is required to assess their safety before they are used clinically. PMID- 1405618 TI - Optimal method for culturing vascular prosthetic grafts. AB - Vascular prosthetic infection may be underrecognized when identified by standard culture techniques. Improved microbiologic methodology may enhance detection of bacteria in prosthetic graft specimens, and thus may alter clinical decisions. Quantitative culture techniques were employed to compare three methods of enhancing bacterial recovery from Dacron graft cylinders seeded with commonly encountered bacterial pathogens. Methods included: (1) ultrasonic bath treatment, (2) direct ultrasonic disruption, and (3) agitation on a Vortex mixer. Ultrasonic bath treatment released bacteria with colony counts that were consistently greater by 1 log than direct ultrasonic disruption and Vortex agitation. Direct ultrasonic disruption at high energy levels selectively killed gram-negative bacteria by as much as a 4 log decrease in viable organisms. Agitation (Vortex mixing) of the specimen produced the lowest counts among the three methods tested. These data would indicate that a 5-min ultrasonic bath treatment was the optimal method of preparation of vascular prostheses for bacterial culture. PMID- 1405619 TI - Magnetic resonance imaging of small arteries. AB - Magnetic resonance imaging (MRI) with receive-only surface coil technology was used to visualize and quantitative luminal diameters of small arteries in the rat. MRI measurements of normal and aneurysmal aortas, over a diameter range of 1 3 mm, were closely correlated with direct measurements made visually at laparotomy: measured differences averaged 0.16 mm, and the least-squares regression line (R2 = 0.97, P < 0.001) compared favorably to the line of equivalence, X = Y. This noninvasive but precise imaging modality demonstrates the potential value of using MRI to evaluate the diameter of small vessels, including the postoperative monitoring of arterial bypass graft patency in peripheral regions. PMID- 1405620 TI - Human gallbladder bile becomes lithogenic during short-term intravenous hyperalimentation. AB - Biliary sludge formation is reported to be one of the complications of intravenous hyperalimentation (IVH); however, the change in human biliary lithogenicity during IVH treatment has been little studied. To clarify the pathogenesis of IVH-induced biliary sludge, we determined biliary lipid composition, vesicular cholesterol concentration, and nucleation time using gallbladder bile samples collected from three groups: The IVH group comprised 9 patients who received IVH with fasting for a period of 2-8 days prior to surgery for gastrointestinal diseases. The control group comprised 10 patients operated after overnight fasting for gastrointestinal diseases. The cholesterol gallstone group comprised 14 patients surgically treated for cholesterol gallstone disease after overnight fasting. The nucleation time in the IVH group was significantly shorter (7.8 +/- 5.3 days, mean +/- SD) than that in the control group (17.3 +/- 5.5 days), while it did not reach the value in the cholesterol gallstone group (3.1 +/- 3.3 days). The cholesterol saturation index in the IVH group (1.01 +/- 0.27) was higher but not significantly different compared with the control group (0.80 +/- 0.21). The concentrations of biliary lipids and individual bile acid were similar in the IVH and control groups. The vesicular cholesterol concentration in the IVH group (3.0 +/- 2.1 mM) was significantly higher than that in the control group (0.9 +/- 1.0 mM). In conclusion, IVH with fasting causes a rapid cholesterol nucleation time and a higher vesicular cholesterol concentration, thereby inducing an initial stage of gallbladder sludge formation. PMID- 1405621 TI - Hypothermia relieves oxidative stress in reperfused skeletal muscle following partial ischemia. AB - The impact of hypothermia on reperfusion-associated oxidative stress in postischemic skeletal muscle was evaluated in a small animal model of high-grade partial ischemia. The infrarenal aorta of heparinized Sprague-Dawley rats was clamped for 90 min, declamped, and then reperfused for 60 min. Previous characterization of this model with 51Cr-tagged microspheres revealed that hindlimb perfusion during aortic clamping continued at 16.6% of baseline values. Resting transmembrane potential difference (Em) and tissue malondialdehyde (MDA), lactate and high-energy phosphate content were determined in hindlimb skeletal muscle at baseline, during ischemia, and upon reperfusion. Four experimental groups (N = 7 in each group) were studied: control animals underwent aortic clamping and declamping; hypothermia animals underwent topical cooling of hindlimbs prior to aortic clamping, with muscle temperatures maintained between 5 and 15 degrees C during ischemia; sham animals underwent midline laparotomy only; and hypothermia-sham animals underwent cooling and midline laparotomy only. During ischemia, resting Em (-mV) was significantly depolarized (P < 0.05 versus baseline) in control (74.9 +/- 0.8 from 91.0 +/- 0.1), hypothermia (64.4 +/- 1.1 from 90.9 +/- 0.3), and hypothermia-sham (67.2 +/- 1.4 from 90.9 +/- 0.4) animals. Upon reperfusion, resting Em remained depolarized in control animals (74.7 +/- 1.6), while repolarization occurred in hypothermia (88.8 +/- 1.1) and hypothermia-sham (90.7 +/- 0.3) animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1405622 TI - Pill-induced esophageal injury. PMID- 1405623 TI - Difficulties in the diagnosis and treatment of drug-resistant tuberculosis and tuberculous empyema. PMID- 1405624 TI - Changing patterns of infectious diseases. PMID- 1405625 TI - Aortoiliac reconstruction following penetrating injury. AB - In summary, there are several factors essential to successful treatment of major vascular abdominal injuries. Prompt resuscitation and abdominal exploration is paramount. Proximal control can quickly be obtained at the esophageal hiatus and adequate exposure of the retroperitoneum is mandatory. Most aortic injuries can be repaired primarily; however, if an arterial substitute is necessary, then PTFE is the substitute of choice. Reimplantation of the injured iliac artery to the contralateral iliac artery is an option for bifurcation injuries if that will not inordinately constrict the lumen. And finally, four-compartment fasciotomies will decompress the lower extremities and prevent ischemic muscle necrosis following reperfusion injury. PMID- 1405626 TI - A patient with cirrhosis and a tan. PMID- 1405627 TI - Radiology case of the month. Acute aortic dissection. PMID- 1405628 TI - OSHA bloodborne pathogens: final rule. PMID- 1405629 TI - Out of his league? PMID- 1405630 TI - Unnatural selection. PMID- 1405631 TI - Cognitive and attitudinal factors in the analysis of alternatives to drunk driving. AB - The present study examined cognitive and attitudinal factors relevant to drunk driving tendencies in individuals having zero, one and multiple drunk-driving convictions. Results indicate that the awareness of consequences of being in an accident was related to driving record but not to drunk-driving tendencies. In contrast, the awareness of consequences of being arrested for drunk driving (e.g., receiving fines, having one's name appear in the news and having a criminal record) was negatively related to drunk-driving tendencies. Attitudes toward alternatives to drunk driving (e.g., take a taxi, call a friend) were also negatively related to drunk-driving tendencies. The findings are discussed with respect to developing prevention programs. PMID- 1405632 TI - The limited utility of BAC for identifying alcohol-related problems among DWI offenders. AB - To see if blood alcohol concentration (BAC) is a significant indicator of problem drinking or an alcohol-related diagnosis, the relationships between BAC at arrest for drinking and driving, typical drinking, alcohol-related problems, problem drinking and an alcohol abuse or dependence diagnosis were examined for 235 drinking and driving offenders referred for alcoholism evaluation. BAC and typical drinking correlated weakly and no significant relationship between alcohol-related problems and BAC was found. Further, no significant relationship was found between BAC and alcohol abuse or dependence diagnoses, or between problem drinking and BAC. These findings cast doubt on the usefulness of a single report of BAC for diagnostic and screening purposes. PMID- 1405633 TI - Drinkers and their driving: compliance with drinking-driving legislation in four Australian states. AB - This study replicates work in Norway and the United States in investigating the extent to which Australian drivers attempt to comply with drinking-driving legislation. In a four-state survey of 1,133 drinkers, it was found that people were aware of the need to control their alcohol input before driving, and derived estimates of blood alcohol after a recent away-from-home drinking occasion demonstrated that the amount people drank was influenced by whether or not they were driving. Drivers reported drinking less than nondrivers and were also those who usually consumed less alcohol. These findings were also true of people with different levels of normal consumption. Although these results are encouraging, it is suggested that there is need for further modification of sanctions, and that the community needs more information about the alcohol content of drinks and drink sizes if people are to moderate effectively their drinking before driving. PMID- 1405634 TI - Citation analysis of 541 articles published in drug and alcohol journals: 1984 1988. AB - Citation histories of 541 articles published in 1984 in 12 drug and alcohol journals were followed through 1988. Considerable variability in mean citation rates across journals was observed. The mean citation rate for the 541 articles was 3.48. Approximately 71% of the articles examined were cited at least once between 1984 and 1988. The present findings suggest that articles published in drug and alcohol journals may be cited more frequently, and exert their influence longer, than those of the social science literature generally. Qualitative analyses suggest that methodological and review articles tend to be cited most frequently. The need for a comprehensive scientometric examination of the drug and alcohol literature is emphasized as is the potential role of multivariate techniques in the identification of variables predictive of individual article and journal citation rates. PMID- 1405635 TI - Self-efficacy, aftercare and relapse in a treatment program for alcoholics. AB - The role of self-efficacy in the prediction of relapse following alcoholism treatment was examined in a 12-month follow-up evaluation. Self-efficacy was assessed at intake to inpatient treatment and again at discharge. The drinking status of male alcoholics completing treatment then was assessed during six intervals over the course of the posttreatment year. Results indicated a significant increase in self-efficacy from intake to discharge. Additional analyses showed that lower intake self-efficacy ratings were associated with relapse by either 6- or 12-months posttreatment. Discharge self-efficacy, on the other hand, was not related to relapse status at either posttreatment point. A subsequent analysis of the pattern of relapses across the six follow-up intervals was conducted using survival analysis. Results revealed that only intake self efficacy was predictive of the follow-up interval during which a relapse occurred. Individuals high in self-efficacy at intake showed the greatest resistance to relapse across time. The maintenance of aftercare further reduced the risk of relapse. The results are discussed with respect to self-efficacy theory and the problem of ceiling effects in posttreatment self-efficacy assessments. PMID- 1405636 TI - A 10-year follow-up survey of acceptability of controlled drinking in Britain. AB - This study was designed to reassess the acceptability of controlled drinking (CD) approximately 10 years after Robertson and Heather's (1982) survey of British treatment providers. Sixty percent of a wide range of almost 300 targeted alcohol service agencies in Scotland, England and Wales responded to a mailed questionnaire. Three-quarters of these respondents reported that nonabstinence was an acceptable outcome goal. About half of the respondents who accept CD reported it as acceptable for only 1-25% of their clientele. Within the subgroup of outpatient agencies, almost one-third reported CD as appropriate for at least 50% of their clientele. Respondents endorsing CD rated severity of dependence, client attitudes and beliefs about controlled drinking and abstinence, drinking history, liver function test results and social stability/social relationships as the most important factors of those listed in selecting outcome goals. Respondents reportedly based acceptance or rejection of CD most frequently on their own professional experience and, to a lesser extent, on research evidence for or against CD and on agency policy. PMID- 1405637 TI - Stages of progression in drug involvement from adolescence to adulthood: further evidence for the gateway theory. AB - Sequential stages of involvement in alcohol and/or cigarettes, marijuana, other illicit drugs and medically prescribed psychoactive drugs from adolescence to adulthood are investigated in a longitudinal cohort that has been followed from ages 15 to 35. Alternative models of progression are tested for their goodness of fit. Four stages are identified: that of legal drugs, alcohol or cigarettes; marijuana; illicit drugs other than marijuana; and medically prescribed drugs. Whereas progression to illicit drugs among men is dependent upon prior use of alcohol, among women either cigarettes or alcohol is a sufficient condition for progression to marijuana. Age of onset and frequency of use at a lower stage of drug use are strong predictors of further progression. PMID- 1405638 TI - Gender patterns in consequences of collegiate alcohol abuse: a 10-year study of trends in an undergraduate population. AB - Although college men have typically reported significantly more alcohol problems than women, debate about a possible convergence of gender differences has emerged in recent years. Time trend data on gender differences based on consistent measures of alcohol-related problems are scant, however. Another limitation of previous research has been the predominant focus on alcohol problems most common among men. This article provides data on gender differences and trends in several types of negative consequences of student drinking in a collegiate population from four surveys conducted between 1979 and 1989. The data do not support an overall "convergence hypothesis" as men remained much more problematic in several types of consequences-specifically abuse problems that are public, involve legal repercussions, or that endanger others. Consequences that are more personal or less prone to provoke public response reveal little or no gender differences, however, in the most recent collegiate cohorts. Thus, more gender research is needed on types of alcohol problems in campus context. PMID- 1405639 TI - Cirrhosis mortality and occupation. AB - Cirrhosis, the ninth leading cause of death in the United States, has been associated with abusive alcohol consumption patterns. Since the workplace serves as a major exposure variable for alcohol consumption over a significant portion of the lifecourse, and since heavy drinking has been shown to differ by type of occupation, this study examines the relationship between type of occupation and cirrhosis mortality. The California Occupational Mortality Study data set (1979 to 1981) provided the information on primary occupation and liver cirrhosis mortality. Crude and sex-specific mortality rates were calculated based on information from a 20% sample of the 1980 California census (included in the data set). Ninety-five percent confidence intervals were calculated around all rates to determine if any were significantly different from rates for the entire state. The findings uphold the view that an association exists between occupation and cirrhosis mortality. The highest mortality rates were found among persons with blue-collar type jobs (e.g., construction laborers and machinists) or jobs where alcohol was easily available (e.g., bartenders and waitresses). Future research needs to specify the factors associated with occupation that may promote the chronic heavy drinking that leads to cirrhosis. PMID- 1405640 TI - Assessment of alcohol-related workplace activities: development and testing of "Your Workplace". AB - Alcohol-related workplace activities are assessed using a short, easy to administer, self-report instrument. Three scales--Adverse Effects of Drinking on Work Performance, Support for Consumption and Support for Abstinence--are derived from it. They have internal reliability, are independent of one another and have face validity as well as discriminant and convergent validities. Some evidence of predictive (criterion-related) validity is presented. Researchers seeking to assess the interrelationship between alcohol-related work factors and drinking behavior can apply this instrument to the task. PMID- 1405641 TI - Measuring quantity and frequency of drinking in a general population survey: a comparison of five indices. AB - This article compares five indices of alcohol consumption in a general population survey conducted in 1985 in the Netherlands. Self-reports of consumption were obtained with a prospective diary, a retrospective 7-day recall method, and three summary measures, such as a quantity-frequency index. The coverage of sales data appeared highest for the diary (67%), which suggests a higher validity. Special attention was given to comparisons of quantity and frequency of drinking between the diary, on the one hand, and the weekly recall and summary measures, on the other. It was found that underreporting, relative to the diary reports, was generally higher in the frequency than in the quantity domain. This result, together with the finding from longitudinal studies that intraindividual variation is also higher for drinking frequency, leads to the conclusion that forgetting is a potent source of undercoverage in surveys and to the hypothesis that large differences in overall drinking pattern between populations (e.g., in regularity of drinking) may account for the large differences in coverage rates of sales data. Furthermore, the subjectively assessed probability of drinking by means of a "usual" frequency question appeared a poor predictor of (diary) drinking frequency for respondents reporting a low or moderate frequency. For subjects claiming a high "usual" drinking frequency, a reasonable correspondence between diary and summary measures was found. This mitigates the fear often expressed that heavy drinkers particularly underreport their consumption. PMID- 1405642 TI - Alcohol availability and consumption: Iowa sales data revisited. AB - Recent changes in Iowa liquor control laws ended the 51-year-old state alcohol monopoly distribution system and turned the sales of bottled wine and spirits over to the private sector. The resulting increase in the availability of these beverages provided a unique opportunity to study the relationship between increased wine and spirits availability and changes in their consumption. Time series analyses of monthly sales (apparent consumption) trends showed that the increased availability had no lasting impact on consumption. PMID- 1405643 TI - The relationship between license type and alcohol-related problems attributed to licensed premises in Perth, Western Australia. AB - Drink-driving offenses, alcohol-related traffic accidents and number of assault charges were used as indicators of the degree of alcohol-related problems associated with individual licensed premises in the Perth Traffic Police region of Western Australia. These indicators were used to rank five main categories of licensed premises according to the levels of harm experienced by their customers while controlling for the amounts of alcohol sold in each category. Nightclubs, taverns and hotels emerged as "high-risk" in comparison with clubs and restaurants. The role of such factors as different customer characteristics, opening hours, types of entertainment, restrictions on clientele and provision of meals are discussed as possible explanations underlying this finding. PMID- 1405644 TI - The effects of alcohol on the cardiovascular stress response in men at high risk for alcoholism: a dose response study. AB - Men at risk for alcoholism appear to be cardiovascularly hyperreactive to stressors; high doses of alcohol have been found to significantly dampen this hyperreactivity. The present study examined the effects of various doses of alcohol on cardiovascular reactivity in high- versus low-risk men. Cardiovascular reactivity to a stressor (unavoidable shock) was examined in men with multigenerational family histories of alcoholism and in family history negative men while they were sober and after they had consumed one of five alcohol doses (active placebo, 0.50, 0.75, 1.00 or 1.32 ml 95% USP alcohol/kg body weight). No significant placebo effects were observed in the active placebo condition. Furthermore, the cardiovascular reactivity dampening effect in high-risk men was evident only at moderate to high doses of alcohol, suggesting that men at high risk for the development of alcoholism must consume moderately high doses of alcohol in order to obtain this potentially reinforcing consequence. PMID- 1405645 TI - Resistance to alcohol impairment of visual-motor performance: does it help to pay attention? AB - In a 2 x 2 factorial design, moderately intoxicated (BAC = .05) college students (n = 40) were exposed to a cognitive set (to concentrate) and/or an auditory feedback signal while performing a modified pursuit-rotor task across five postbeverage trials. Self-reported "highness" was also assessed. A control group received placebo drinks and performed without aids. Hypothesized main effects for both set and signal revealed that intoxicated aided subjects outperformed their unaided counterparts. Moreover, subjects who received both aids outperformed all other intoxicated subjects and performed equivalently with unaided placebo subjects. Separate analyses of the first postbeverage trial and use of covariance analyses provided confidence that the obtained effects were not attributable to acute or chronic tolerance. Highness correlated negatively with performance; but set and signal effects on highness failed to reach significance. Although alcohol induced motor impairment is not recognized in the research literature as being under volitional control, subjects in the present study exhibited clear resistance to alcohol impairment. Possible psychological mediators and moderators of the obtained effects are discussed, as well as the relevance of these findings for tolerance research. Practical implications are also considered. PMID- 1405646 TI - Resource-limited information processing in alcoholism. AB - A concurrent-task paradigm was utilized to examine the availability of limited capacity information-processing resources in long-term chronic alcoholism. Normal control subjects and detoxified long-term alcoholics did not differ in their performance of a primary task that required an assessment of the meaning of foveally-presented words. However, reaction time measures indicated that the abstinent alcoholics were relatively impaired in their ability to concurrently perform a secondary task that required them to detect randomly-occurring and spatially-distributed visual probe stimuli. This impairment is interpreted as reflecting an abnormal limitation in the attentional resources abstinent alcoholics have available for task performance. The relationship between this deficit and the types of biological abnormalities and neuropsychological impairments commonly observed in alcoholism is discussed. PMID- 1405647 TI - Ultrastructural alterations in ileal M cells of rats after chronic ethanol ingestion: reversal after cessation of ethanol. AB - Membranous (M) cells within the dome epithelium of ileal Peyer's patches have been shown to provide selective antigen entry for mucosa-associated lymphoid tissue. This study produced morphologic evidence of ethanol-induced disruption of the architecture in follicle-associated epithelium. The adherens type junctions of the lateral plasma membranes between M cells and columnar absorptive cells were disrupted. A 45-day exposure by ingestion of ethanol also produced marked changes in the ultrastructure of M cells. All experimental animals showed mitochondrial swelling with loss of matrix density, dilation of the endoplasmic reticulum and cytoplasmic vacuolization. The ethanol content of serum and chyme samples were 180 mg/dl and 160 mg/dl, respectively. This was well below the 4,280 mg/dl of the diet therefore a systemic mechanism was implicated for the changes observed. Membranous cells from the recovery group were normal 15 days after withdrawal from ethanol. We concluded that the ethanol-induced cytopathology in ileal M cells is reversible when ethanol exposure is discontinued. PMID- 1405648 TI - Prognostic factors for noncurative gastric cancer: univariate and multivariate analyses. AB - We performed univariate and multivariate analyses of possible prognostic factors related to postoperative clinical course of patients with advanced gastric cancer. Noncurative resection was done for 119 patients with hepatic metastasis, peritoneal seeding, extensive lymph node metastasis, or direct invasion to adjacent organs, either alone or in various combinations. In the univariate analysis, 6 of 17 items such as peritoneal seeding, lymphatic invasion, vascular invasion, mode of invasion, extent of lymphadenectomy, and width of serosal invasion significantly correlated to the prognosis. The multivariate analysis indicated that three inherent pathologic factors, mode of invasion, lymph node metastasis, and hepatic metastasis, and one treatment factor, extent of lymphadenectomy, were significant variables predictive of the prognosis and that the prognosis was expected to be very poor in cases of infiltrative type, nodal involvement to tertiary nodes, presence of hepatic metastasis, and lymphadenectomy less than R3. Prognosis in terms of the extent of lymphadenectomy shows that extensive lymphadenectomy (R3) proved to be significantly effective in prolonging survival time, even after noncurative gastrectomy. We recommend extensive lymphadenectomy to prolong survival time for such patients. PMID- 1405649 TI - Skeletal metastasis from occult carcinoma. AB - We reviewed 177 patients with skeletal metastases, seen between 1984 and 1989, to define the characteristics of metastatic bone disease from an occult primary carcinoma. In 52 (30%) patients, the primary carcinomas could not be identified when the bone metastases were first diagnosed. This group was predominantly male, with intractable pain the most common symptom. The primary tumors were identified on antemortem evaluation in 28 (54%) patients after extensive examination. Among these, the primary tumor was in the lung in 9 patients, followed by liver (8), kidney (5), prostate (3), thyroid gland (2), and rectum (1). The identifiable occult malignancies possessed three common features: all were osteophilic tumors, all had a high incidence in the specific geographic area, and all were not amenable to early detection. The mean survival of these patients was 11 months. Current treatment modalities failed to affect the course of these patients, except for those with primary carcinomas of the kidney and prostate. This observation attests to our limitations in both the diagnosis and treatment of this problem. Efforts should be directed primarily toward excluding those common and/or treatable tumors only. PMID- 1405650 TI - Early gastric cancer: an analysis of 44 cases with emphasis on the prognostic significance of the macroscopic and microscopic growth patterns. AB - Forty-four consecutive cases of "early gastric cancer" were studied according to the macroscopic classification proposed by the Japanese Gastroenterological and Endoscopy Society and further analyzed in terms of growth patterns. The tumours were then classified into the small mucosal type, the superficially spreading (Super) type and the penetrating growth (Pen) type. The Lauren type (intestinal vs. diffuse), presence of lymphatic and venous invasion, and lymph node metastasis were also assessed. Most elevated tumours showed a superficial growth pattern and were classified as Lauren's intestinal type, whereas depressed lesions were associated with submucosal invasion and were classified as diffuse. Microscopic patterns did not show any correlation with Lauren's classification. Mean duration of follow-up was 67.8 months and the overall actuarial survival was 93%, 80%, and 72%, at 2, 5, and 10 years, respectively. Aside from venous invasion no correlation was found between survival and any of the morphological parameters analysed. PMID- 1405651 TI - Hepatic resection following systemic chemotherapy for metastatic colorectal carcinoma. AB - Increasingly effective systemic chemotherapy has improved responses in patients with previously unresectable colorectal hepatic metastases. In the future, response to chemotherapy may define a new population of patients that may benefit from hepatic resection. A retrospective review to determine the safety and effectiveness of potentially curative hepatic resection of metastatic colorectal carcinoma after systemic chemotherapy identified 11 such patients with resections between July 1987 and October 1991. Five patients had unresectable disease confined to the liver, two had hepatic and limited extrahepatic metastases, two had hepatic recurrences after previous hepatic metastasectomy, and two had initially resectable liver metastases. These patients were resected after a mean of 8 months of systemic chemotherapy. Complications, usually minor, occurred in five patients (45%). There were no deaths. Three patients are disease free at 15, 18, and 31 months (mean 21) after hepatic resection. Eight patients have recurred with a median time to recurrence of 8 months. Five patients have subsequently died of recurrent disease. This study suggests that hepatic resection following systemic chemotherapy can be performed safely and may benefit selected patients. PMID- 1405652 TI - Therapeutic gain of local and radical resection combined with postoperative radiation for murine fibrosarcomas. AB - Resection of 8-mm fibrosarcomas (FSaII) growing in the right leg of syngeneic C3H/Sed mice was performed under a dissecting (x8) microscope. Local and radical resection achieved 20% (5/25) and 48% (12/25) tumor control, respectively. TCD80s (average dose expected to control 80% of irradiated tumors) for radiation alone given as one fraction per day for 5 consecutive days were 73.1 and 118.0 Gy for the microscopic and 8-mm tumors, respectively. Radiation therapy started at 4 or 7 days following local or radical resection enhanced both the local tumor control and the treatment-related morbidity represented by leg shortening. From enhancement ratios (ERs) for tumor control (TCD80 for radiation alone/TCD80 for postoperative radiation) and for leg shortening (dose for 5-mm leg shortening for radiation alone/postoperative radiation) values, therapeutic gain factors (TGFs) were derived as ER tumor/ER leg shortening. These were 1.3 and 1.4 for local and radical resection followed by radiation started on the 7th postoperative day, respectively. Corresponding figures for radiation started on the 4th postoperative day resulted in 1.2 for both resection procedures. PMID- 1405653 TI - Secondary penile malignancies: the spectrum of presentation. AB - Secondary penile carcinoma is a rare disease with signs and symptoms covering a wide spectrum, from simple erythema to priapism. We report two cases of penile metastatic involvement that are illustrative of this spectrum. PMID- 1405654 TI - Malignant melanoma in a child with oculocutaneous albinism. AB - Malignant melanoma is extremely rare in patients with albinism. To date, in the English language literature, there have been only sixteen documented cases of malignant melanoma in albino patients. These cases include thirteen cutaneous, one oral, one ocular, and one anal; only one of these was in a child. Here, we present the case of the youngest known albino patient to have cutaneous malignant melanoma. PMID- 1405655 TI - Poorly differentiated solid type adenocarcinomas in the stomach: a clinicopathologic study of 71 cases. AB - A review of 71 cases of solid carcinoma of the stomach selected from 2,738 cases of surgically resected poorly differentiated adenocarcinomas (PDAs) was undertaken. The average age of the patients, which included 47 men and 24 women, was 62 years. The clinicopathologic features of solid carcinomas were similar to those of the differentiated type adenocarcinomas. The solid carcinomas were divided into 42 of the solid alveolar type and 29 of the free-cell type; 32 of the former (76%) had foci of overt differentiated areas, while most of the latter type lacked such foci and had some signet-ring cells. Many tumors of both types had a prominent venous permeation and lymph node metastasis even in the early stage of invasion. The 5-year survival rates were 37% in all cases, 44% in cases with carcinoma with a limited invasion of the submucosa or the muscularis propria, and 27% in carcinoma invading down to the subserosa. These survival rates were poor in comparison with the 110 cases of ordinary PDA (diffuse type of Lauren) selected as controls. These findings suggest that tumors of the solid alveolar type are transformed from the differentiated type of adenocarcinoma, while those of the free-cell type are originally from PDAs. It is also suggested that solid carcinomas did show a high incidence of venous permeation and lymph node metastasis and that the prognosis for of venous permeation and lymph node metastasis and that the prognosis for this type of carcinoma is poor. PMID- 1405656 TI - Inferior vena cava leiomyosarcoma. AB - Leiomyosarcoma of the inferior vena cava is a rare malignancy, and radical resection with negative margins remains the only hope for cure. In this report we cite four cases of this tumor treated at The University of Texas M.D. Anderson Cancer Center with particular emphasis on the use of preoperative chemotherapy. In our patients, preoperative chemotherapy did not adversely affect operative outcomes or survival. The potential benefits of preoperative chemotherapy include control of micrometastases, reduction in tumor size before resection, and in situ evaluation of tumor response to chemotherapy for postoperative adjuvant therapy. PMID- 1405657 TI - Surgical treatment for thoracic esophageal carcinoma in patients after gastrectomy. AB - The clinicopathologic factors in 50 gastrectomized and 831 nongastrectomized patients with thoracic esophageal carcinoma were compared. The differences in various factors were not statistically significant except for the average duration of operation, which suggests that the association of esophageal carcinoma and previous gastrectomy is a chance finding. Thirty-four gastrectomized patients underwent abdominal lymphadenectomy and 16 did not. The postoperative survival curves for the two groups did not differ. In comparing the clinicopathologic factors between the two groups, only the tumor location differed significantly (P < .05). Nine patients (26.5%) with lesions in the mid- or lower thoracic esophagus in the gastrectomized group had positive nodes in the abdomen; the 5-year survival rate was 39.4%. Among them, 8 had gastrectomy for peptic ulcer. Abdominal lymphadenectomy is recommended for those patients with mid- or lower thoracic esophageal carcinoma who have had previous gastrectomy without lymphadenectomy. PMID- 1405658 TI - Use of the Carpentier-Edwards porcine bioprosthesis: assessment of a patient selection policy. AB - The Carpentier-Edwards bioprosthesis was implanted in 369 patients (414 valves) between May 1977 and December 1987 (age 67.2 +/- 0.5 years); 242 had aortic valve replacement, 80 had mitral valve replacement, 44 had multiple valve replacement, of which 41 were aortic and mitral valve replacement, 2 had isolated tricuspid valve replacement, and 1 had a pulmonary valve replacement. The selection criteria were the following: shorter life expectancy (253 patients) or contraindications to anticoagulants for organic (113 patients) or psychologic (38 patients) reasons, or both. The early mortality rate was 11.1% (aortic valve replacement, 9.1%; mitral valve replacement, 12.4%; aortic and mitral valve replacement, 23.1%). Total cumulative follow-up was 1456 pt-yr (mean 4.4 years, range 1 to 148 months), and the patient evaluation was 99.5% complete. Late mortality was 4.9%/pt-yr. Five-year survival was 70.4% +/- 2.7% overall, 74.3% +/ 3.2% after aortic valve replacement, 60.9% +/- 6.2% after mitral valve replacement (p < 0.03), and 60.7% +/- 8.1% after aortic and mitral valve replacement. Eight patients were reoperated on for primary tissue failure, and freedom from reoperation for structural valve deterioration was 97.5% +/- 1.2% at 5 years and 95.6% +/- 1.8% at 8 years. Failing aortic bioprostheses were explanted in four patients (0.4%/pt-yr) and mitral bioprostheses in seven (1.6%/pt-yr). No patient whose valve was inserted after the age of 70 had to be reoperated on for structural valve dysfunction. The probability of freedom from thromboembolism after 5 and 8 years of follow-up was 93.1% +/- 1.6% and 92.2% +/- 1.8%, respectively. The prevalence of anticoagulant-related hemorrhage was 0.8%/pt-yr (major 0.6%, minor 0.2%). Anticoagulants had to be maintained in 16.3% of the patients: 5.9% after aortic valve replacement, 35.7% after mitral valve replacement, and 45.8% after aortic and mitral valve replacement, while 80.0% were on a regimen of antiplatelet drug therapy. Prosthetic valve endocarditis happened in five patients (0.3%/pt-yr). Freedom from all valve-related morbidity and mortality, including hospital deaths, was 71.0% +/- 2.7% at 5 years and 58.6% +/- 4.6% at 8 years and was significantly better in the aortic valve replacement group (61.3% +/- 6.6% at 8 years) compared with the mitral valve replacement group (54.4% +/- 7.7% at 8 years; p = 0.04). This study confirms the satisfactory performance of the Carpentier-Edwards valve after aortic valve replacement in elderly patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1405659 TI - Hemodynamic evaluation of the Monostrut and spherical disc Bjork-Shiley aortic valve prosthesis with Doppler echocardiography. AB - A Doppler echocardiographic study was performed to assess whether the Monostrut model of the Bjork-Shiley valve (Shiley, Inc., Irvine, Calif.) had an improved hemodynamic performance in comparison with the spherical disc model in the aortic position. Twenty retrospectively randomly selected patients were studied, 10 with each valve type. Within each valve type two sizes of valve were studied, 21 and 23 mm. The two groups were comparable with respect to age, postoperative time, fractional shortening, New York Heart Association functional class preoperatively, and body surface area. Pulsed and continuous wave Doppler measurements were recorded at rest. Continuous wave Doppler recordings were performed every 2 minutes after exercise with supine bicycle ergometry until 10 minutes after exercise. Peak and mean gradients across the aortic valve prostheses were estimated. Both groups achieved a significant and comparable rise in heart rate with exercise. The mean gradients +/- standard error of the mean at rest and 2 minutes after exercise were 19.7 +/- 1.9 mm Hg and 30.9 +/- 2.2 mm Hg, respectively in the spherical disc group compared with 14.9 +/- 1.1 mm Hg and 23.6 +/- 1.7 mm Hg in the Monostrut group (p < 0.05 and p < 0.025, respectively). Peak transvalvular gradient at rest was 30.7 +/- 2.7 mm Hg in the spherical group compared with 23.9 +/- 1.9 mm Hg in the Monostrut group (p < 0.05). We conclude that the Monostrut Bjork-Shiley valve prosthesis has better hemodynamic performance than the spherical disc model in the aortic position. PMID- 1405660 TI - Preoperative and postoperative right ventricular function during exercise in patients with mitral stenosis. AB - To elucidate the effects of mitral valve surgery on right ventricular function in 11 patients with mitral stenosis, pre- and postoperative right ventricular function were quantified using gated equilibrium blood pool radionuclide ventriculography at rest and during exercise. The preoperative right ventricular ejection fraction was 39 +/- 4% at rest and 36 +/- 9% during exercise, which during exercise was lower than control values (51 +/- 5%) (p < 0.01). When the preoperative right ventricular ejection fraction was lower during exercise than at rest, postoperative right ventricular ejection fraction during exercise was lower than normal values (42 +/- 3% versus 51 +/- 5%) (p < 0.01). When the preoperative right ventricular ejection fraction did not decrease during exercise, the postoperative right ventricular ejection fraction was within normal limits during exercise (54 +/- 5%). In addition, postoperative right ventricular ejection fraction during exercise increased to normal values in patients whose preoperative right ventricular ejection fraction during exercise had been 40% or higher. Preoperative peak ejection rate was -1.81 +/- 0.19 EDV/sec at rest and 1.72 +/- 0.39 EDV/sec during exercise, which during exercise was lower than control values (-2.44 +/- 0.53 EDV/sec) (p < 0.01). Postoperatively, peak ejection rate during exercise (-2.50 +/- 0.37 EDV/sec) increased (p < 0.05) to normal levels. Preoperative peak filling rate was 1.61 +/- 0.47 EDV/sec at rest and 1.88 +/- 0.54 EDV/sec during exercise, which during exercise was lower than control values (2.58 +/- 0.62 EDV/sec) (p < 0.01). Postoperatively, peak filling rate during exercise (2.82 +/- 0.62 EDV/sec) increased (p < 0.05) to normal values in all patients. Preoperative changes in both right ventricular ejection fraction and peak ejection rate from rest to exercise inversely correlated with the preoperative pulmonary vascular resistance at rest (right ventricular ejection fraction, r = -0.79, p < 0.005; and peak ejection rate, r = -0.67, p < 0.05). In conclusion, right ventricular systolic function improved in about half of the patients with mitral stenosis, and diastolic function improved in all patients during exercise following surgery. When the preoperative pulmonary vascular resistance was elevated, the right ventricular systolic dysfunction persisted. PMID- 1405661 TI - Surgery for atrioventricular node reentry tachycardia. Results with surgical skeletonization of the atrioventricular node and discrete perinodal cryosurgery. AB - Surgical treatment options for interruption of atrioventricular node reentrant tachycardia include (1) skeletonization of the atrioventricular node by dissecting it from most of its atrial inputs and (2) discrete cryosurgery of the perinodal tissues by applying a series of sequential cryolesions to the atrial tissues immediately adjacent to the atrioventricular node. Both these techniques attempt to interrupt one of the dual atrioventricular node conduction pathways while preserving the other. This report describes 17 consecutive patients who underwent surgical treatment, 10 patients with skeletonization of the atrioventricular node and seven patients with discrete perinodal cryosurgery. There were 10 female and seven male patients and their ages ranged from 28 to 56 years (mean 38). Two of the 17 patients had Wolff-Parkinson-White syndrome and their accessory pathways were interrupted before the atrioventricular nodal reentrant tachycardia was ablated. All the procedures were performed in a normothermic beating heart while atrioventricular conduction was monitored closely. In the skeletonization technique, the right atrial septum was mobilized and the atrioventricular node exposed anterior to the tendon of the Todaro. The perinodal cryosurgical procedure was also performed through a right atriotomy and a series of sequential 3 mm cryolesions were placed around the borders of the triangle of Koch on the inferior right atrial septum. There were no operative deaths. Two patients who underwent the skeletonization operation had heart block necessitating pacemaker therapy. At postoperative electrophysiologic study, no echoes or atrioventricular nodal reentrant tachycardia were inducible in any of the 17 patients. All patients have remained free of arrhythmia recurrence and have required no antiarrhythmic therapy after a follow-up of 5 to 28 months (mean 14). In conclusion, both atrioventricular node skeletonization and perinodal cryosurgery successfully ablate atrioventricular nodal reentrant tachycardia; however, perinodal cryosurgery appears to be safer in avoiding heart block, is more easily performed, and is our procedure of choice for the management of medically refractory atrioventricular nodal reentrant tachycardia. PMID- 1405662 TI - Quantitation of mapping uncertainty in Wolff-Parkinson-White syndrome. Implications for anatomic characterization and surgical division of accessory atrioventricular connections. AB - The purpose of this study was to quantitate the uncertainty inherent in the electrophysiologic mapping of ventricular preexcitation as seen in Wolff Parkinson-White syndrome. An ink-coated needle electrode was constructed to serve as a point source of unipolar stimulation along the atrioventricular junction. Activation times for 11 ventricular mapping sites at the atrioventricular junction were measured for each stimulation point. Maps were successfully completed for 18 right free wall and 14 posterior septal stimulation points. The activation time at the mapping site closest to the stimulation point was termed the index activation time. Activation times identical to the index activation time were noted at 1.3 +/- 0.5 mapping sites for each free wall stimulation point and 1.9 +/- 0.9 mapping sites for each septal stimulation point (p < 0.05, septal versus free wall stimulation points). Activation times falling within 5 msec of the index activation time were noted at 2.4 +/- 1.0 mapping sites for each free wall stimulation point and at 3.9 +/- 1.4 mapping sites for each septal stimulation point (p < 0.05, septal versus free wall stimulation points). The uncertainty of electrophysiologic mapping can be quantitated, and this error should be considered when making inferences regarding the anatomy of accessory pathways based on electrophysiologic data. A knowledge of the uncertainty inherent in the localization of accessory atrioventricular connections by electrophysiologic mapping can be used to plan borders of surgical dissection that will account for this uncertainty at a 95% confidence level. PMID- 1405663 TI - Mid-infrared pulsed laser ablation of the arterial wall. Mechanical origin of "acoustic" wall damage and its effect on wall healing. AB - Pulsed mid-infrared lasers are an alternative to excimer lasers for transluminal angioplasty. The mid-infrared lasers, however, were reported to produce "acoustic" wall damage that might impair the immediate and long-term results. To study the immediate and long-term effects on the arterial wall, 184 craters (1 mm diameter and 1 mm depth) were produced perpendicular to the intimal lining in the thoracic aortas of pigs. Three types of craters were evaluated: Ho-YSGG laser induced (lambda = 2.09 microns, 2 pulses of 500 microseconds, 0.50 joule/pulse, 50 gm force), mechanically drilled, and "acoustic" craters. "Acoustic" craters were produced by two laser pulses delivered into a saline-filled metal fiber cap, which was placed in a mechanically drilled crater. The metal cap was provided with four outlets for water vapor and isolated "acoustic" from optical and thermal laser effects. The pigs survived 3, 14, and 28 days. Arterial wall damage, medial necrosis, and wall healing were assessed microscopically. At 3 days, laser and "acoustic" craters were accompanied by large tissue ruptures (2.7 +/- 0.9 mm and 2.9 +/- 0.8 mm, respectively, mean +/- standard deviation). These were attributed to large vapor bubbles expanding within the tissue. A zone of medial necrosis was observed adjacent to the laser craters (0.43 +/- 0.15 mm) and to the "acoustic" craters (0.17 +/- 0.14 mm). Neither ruptures nor necrosis was observed with the mechanical craters. At 2 and 4 weeks, the necrotic areas were repopulated with smooth muscle cells and all craters were adequately filled with smooth muscle cells, without any sign of an exaggerated proliferative response. We conclude that within the arterial wall, Ho-YSGG ablation was accompanied by the rapid expansion of a water vapor bubble. The formation of the relatively large vapor bubble is inherent to the use of a mid-infrared laser. The risk of creating dissections clinically, when delivering Ho-YSGG laser pulses, remains to be determined. The present study provided no indication that the arterial wall fissures might affect the restenosis rate unfavorably by promoting myointimal proliferation. PMID- 1405664 TI - Current trends in lung transplantation. Lobar transplantation and expanded use of single lungs. AB - Heart-lung transplantation remains the only therapeutic option for patients with combined end-stage cardiopulmonary disease. Because of the scarcity of heart-lung donors, we have been investigating other surgical alternatives for patients with end-stage vascular and parenchymal lung disease. From June 1989 through June 1991, 48 patients underwent pulmonary transplantation. Seventeen of the 48 patients underwent single lung transplantation. Of the 17 patients in the single lung group, eight patients had pulmonary hypertension and nine had parenchymal lung disease. Four of the 17 patients underwent repair of a cardiac defect with single lung transplantation. One-year actuarial survival was 68%. Pulmonary function has been excellent. The forced expiratory volume in 1 second was 79.6 +/ 13.6 (percent predicted), forced expiratory flow 25%-75% was 72.6 +/- 14.5 (percent predicted), and arterial oxygen tension was 82.8 +/- 10.06 mm Hg when measured at annual follow-up in a group of eight patients without obliterative bronchiolitis. Pulmonary artery pressures of systemic level or greater in the group with pulmonary vascular disease were normal at annual catheterization. Most patients had at least one episode of allograft rejection. Actuarial freedom from rejection at the end of 3 months was 30%. Three of the 17 single lung patients receiving lung lobes were children. Two children received living-related lobe transplants and one neonate received a lobe from a 2-year-old cadaver donor. Single lung transplantation is an effective therapeutic option for selected patients with vascular or parenchymal lung disease. Expanding indications will permit more individuals to receive transplants from the existing donor pool. Living-related and cadaver lobe transplantation will also increase the options available to children in need of lung transplantation. PMID- 1405665 TI - An experimental study on direct revascularization of bronchial circulation by microvascular anastomosis. AB - The effects of direct revascularization of the bronchial artery after bronchoplasty were estimated by laser Doppler velocimetry and india ink injection in dogs. Bronchoplastic surgery at the right main bronchus was performed in all dogs, and the bronchial artery was reconstructed using the internal thoracic artery in the reconstruction group. The mucosal blood flow was measured at the distal side of the anastomosis. India ink was injected into the aorta in the nonreconstruction group and into the internal thoracic artery in the reconstruction group. The peripheral blood flow had diminished immediately after surgeries to 59% of the baseline value and took 14 days to recover to the baseline value in the nonreconstruction group. However, in the reconstruction group, the blood flow recovered at once to 78% of the baseline value and had returned to that value in 5 days. Statistically significant differences were noted between the groups from just after operation to day 7. India ink data confirmed these findings. In the nonreconstruction group, no ink was observed in the peripheral bronchial vessels on day 3; it was noted in part of the vessels on day 7 and in most on day 14. On the other hand, a relatively large number of vessels were stained just after operation in the reconstruction group. Thus reconstruction of the bronchial artery by means of the anastomosis with the internal thoracic artery can be said to be a useful and effective method for preventing airway ischemia. PMID- 1405666 TI - Reliable thirty-hour lung preservation by donor lung hyperinflation. AB - We examined the hypothesis that the degree of inflation of the lungs at the time of harvest may have an important role in postpreservation function. Lungs of donor dogs randomly assigned to groups 1 (n = 5) and 2 (n = 5) were ventilated with large tidal volumes (tidal volume, 25 ml/kg; positive end-expiratory pressure, 5 cm H2O; respiratory rate, 12 breaths/min, inspired oxygen fraction 1.0) and were inflated to 30 cm H2O for 15 seconds before pulmonary artery flush and again immediately before tracheal crossclamping. In group 3 (n = 5) donor lungs were normally ventilated (tidal volume, 12.5 ml/kg, positive end-expiratory pressure 0 cm H2O; respiratory rate 12 breaths/min, inspired oxygen fraction, 1.0) and were not hyperinflated before pulmonary artery flushing; the trachea was crossclamped at end-inspiration. In groups 1 and 3 a large bolus (25 micrograms/kg) of prostaglandin E1 was injected into the pulmonary artery before flushing and was also added to the pulmonary artery flush solution (500 micrograms/L). A rapid (approximately 50 seconds), high-volume mm Hg), hypothermic (4 degrees C) pulmonary artery flush was performed in all hypothermic (4 degrees C) pulmonary artery flush was performed in all groups with modified Euro-Collins solution. Heart-lung blocks were stored at 4 degrees C for approximately 29 hours before left single lung allografting. An inflatable cuff was placed around the recipient right pulmonary artery, allowing independent study of the transplanted lung. Hyperinflated lungs harvested with or without prostaglandin E1 provided equivalently excellent early posttransplant function (arterial oxygen tension [mean +/- standard deviation]: group 1; 503 +/- 45, vs group 2; 529 +/- 150 mm Hg; inspired oxygen fraction 1.0). Mean arterial oxygen tension was significantly lower in group 3 (116 +/- 78 mm Hg) than in either groups 1 or 2 (p < 0.0002 for either comparison). Copious reperfusion pulmonary edema was a constant feature in group 3 but was not seen in groups 1 and 2. All 10 recipients in groups 1 and 2 survived the 3-day assessment period without difficulty; two of the five recipients in group 3 died during initial unilateral perfusion of the transplanted lung. Donor hyperventilation and inflation to 30 cm H2O before hypothermic storage can help provide excellent posttransplantation lung function after 30-hour preservation, with or without prostaglandin E1 pretreatment. We speculate that this improvement may be due to effects of increased lung volume on pulmonary vascular tone and/or surfactant metabolism. PMID- 1405667 TI - Effects of the pericardium on left ventricular diastolic filling and systolic performance early after cardiac operations. AB - To determine whether closure of the pericardium after cardiac operations affects the filling characteristics and systolic performance of the left ventricle, we measured left ventricular volume, pressure, cardiac index, and stroke work index in 10 patients between 11 and 15 hours after cardiac operations, with the pericardium first closed and then open. At the time of operation, radiopaque tantalum markers were inserted in the left ventricular myocardium to outline the chamber in the 30-degree right anterior oblique projection, and the pericardium was closed by a continuous polypropylene suture exteriorized at both ends of the sternotomy. The patient was then transferred to the surgical intensive care unit, where left atrial pressure was measured via a fluid-filled catheter, left ventricular pressure with a micromanometer-tipped catheter, and myocardial oxygen consumption via a coronary sinus catheter. Left ventricular volume was measured by computer-aided analysis of fluoroscopic images (recorded at 30 frames per second) of the implanted myocardial markers. Left atrial pressure was maintained at target values of 10, 15, and 20 mm Hg by intravenous augmentation of blood volume. Left ventricular and left atrial pressures and volumes were measured with the pericardium closed; the pericardium was then opened by withdrawal of the pericardial suture. Radiopaque clips on the pericardial edges confirmed opening of the pericardium seconds after withdrawal of the suture. Repeated measurements of left ventricular pressures and volumes were then made at the target left atrial pressures with the pericardium open. End-diastolic volume index, peak positive time derivative of pressure, stroke work index, and cardiac index all increased significantly when the pericardium was opened (p < 0.001). Thus we found the following: (1) At physiologic pressures, the pericardium had a significant constraining effect on diastolic filling of the left ventricle, and (2) opening of the pericardium resulted in increased cardiac index and stroke work index. These increases may be attributed to the Frank-Starling response to increased left ventricular preload. The demonstrated improvement in left ventricular systolic performance should be considered when contemplating closure of the pericardium after cardiac operations, especially in patients with preoperative left ventricular dysfunction. PMID- 1405668 TI - Homologous blood transfusion as a risk factor for postoperative infection after coronary artery bypass graft operations. AB - Homologous transfusions are immunosuppressive and associated with a higher risk of postoperative infection. In this retrospective analysis, we studied 238 consecutive patients who underwent first-time coronary operations by a single surgeon in 1988 to 1989 and collected clinical and laboratory data relevant to postoperative infections including pulmonary, urinary, and wound sites. Culture proved postoperative infections occurred in 16 of the 238 patients (6.7%), with only 3 (1.3%) being deep sternal wound infections. Seven of 16 (44%) of the infections were away from the wound sites, suggesting that nonsurgical variables contributed to at least some infections. Factors significantly associated with an increased risk of postoperative infection by univariate analysis included female sex, diabetes mellitus, and transfusion dose. Infections occurred in 3.9% of patients receiving up to 2 units of red cells and whole blood, 6.9% receiving 3 to 5 units, and 22% of those receiving 6 units or more. Multiple linear and logistic regression analysis showed that transfusion dose was the most significant predictor of infection, days of fever, days of antibiotic therapy, and length of hospital stay. Homologous transfusion is associated (in a dose dependent fashion) with a threefold to eightfold increased risk of postoperative infection in patients undergoing coronary artery operations. This increased risk of infection may be due to transfusion-induced immunosuppression of the patient. PMID- 1405669 TI - Spinal cord protection with intravenous nimodipine. A functional and morphologic evaluation. AB - The purpose of this study is to determine the effects of ischemia in the spinal cord when a calcium channel blocker, nimodipine, is administered intravenously before, during, and after crossclamping of the thoracic aorta. In this series of experiments, 18 pigs underwent thoracotomies and had 17.5 to 18.0 cm of the thoracic aorta clamped for 30 minutes. By random selection, nine animals received intravenous nimodipine (2 micrograms/kg per minute) and nine control animals received only a carrier solution. Of the nine animals that received nimodipine, eight walked after the operation. In contrast, in the control group only two of nine animals walked. The ninth nimodipine-treated animals walked but had a severe delayed deterioration response. All animals, except one control animal, had a negative central spinal perfusion pressure. Morphologic examination of serial sections of spinal cords from control animals showed diffuse neuronal necrosis. In comparison, cords from the nimodipine group had swollen neurons accompanied by an inflammatory infiltrate and only occasional necrotic neurons. With this data, we conclude that certain calcium channel blockers, when administered in sufficient doses, can lend a protective effect to the spinal cord during ischemic events even when cord perfusion pressure has dropped to dangerously low levels. PMID- 1405670 TI - Simple hypothermic retrograde cerebral perfusion during aortic arch replacement. A preliminary report on two successful cases. AB - We recently found that hypothermic retrograde cerebral perfusion can be performed by simply elevating the central venous pressure in Trendelenburg's position while the aortic arch is open. In this technique, with an occlusion balloon in the descending aorta, deep hypothermic perfusion of the lower half of the body is performed as oxygen-rich venous blood supplies the brain. Two successful cases are reported: one of dissecting aortic aneurysm, DeBakey type II, with a true aortic arch aneurysm, in a 53-year-old woman, and one of acute aortic dissection, DeBakey type I, in a 53-year-old man. With the brain under retrograde perfusion at a rectal temperature of 15 degrees C and a central venous pressure of 15 mm Hg, replacement of the ascending to the descending aorta in the former case and to the proximal aortic arch in the latter case was successful. Cerebral circulatory arrest times were 81 and 65 minutes, respectively. No neurologic deficit was found postoperatively. It is suggested that this simple technique protected the brain for a long period of cerebral circulatory arrest during the aortic arch operation by supplying it with oxygen and simplifying the operative procedure. PMID- 1405671 TI - Cardiopulmonary bypass and the blood-brain barrier. An experimental study. AB - The diffuse inflammation produced by cardiopulmonary bypass might disrupt the blood-brain barrier and lead to the transient neurologic dysfunction occasionally seen after cardiac operations. To evaluate this possibility, blood-brain barrier integrity was measured by carbon 14-aminoisobutyric acid tracer technique after 2 hours of cardiopulmonary bypass in piglets. Six animals were cooled to 28 degrees C on cardiopulmonary bypass and then rewarmed to 38 degrees C before carbon 14 aminosisobutyric acid was injected intraarterially. A control group of six animals underwent median sternotomy and heparinization but were not placed on cardiopulmonary bypass. Blood-to-brain transfer coefficients for carbon 14 aminosisobutyric acid were calculated for multiple brain regions; higher coefficients reflect greater flux of carbon 14-aminosisobutyric acid and suggest loss of blood-brain barrier integrity. The brain regions examined and their transfer coefficients (cardiopulmonary bypass versus control mean +/- standard error of the mean ml/gm/min) were middle cerebral artery territory cortex (0.0032 +/- 0.0002 versus 0.0030 +/- 0.0002; p = 0.42), diencephalon (0.0031 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.50), midbrain (0.0028 +/- 0.0002 versus 0.0027 +/ 0.0002; p = 0.86), cerebellum (0.0036 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.22), and spinal cord (0.0035 +/- 0.0003 versus 0.0041 +/- 0.0008; p = 0.48). There were no significant differences in transfer coefficients between animals placed on cardiopulmonary bypass and control animals in any brain region examined. The pituitary gland lacks a blood-brain barrier and had a correspondingly high coefficient in control animals and those undergoing cardiopulmonary bypass (0.077 +/- 0.012 versus 0.048 +/- 0.008; p = 0.07). Two hours of moderately hypothermic cardiopulmonary bypass does not disrupt the blood brain barrier. PMID- 1405672 TI - Patient memory before and after cardiac operations. AB - The memories of 20 patients undergoing elective operations on the heart were assessed by a comprehensive battery of standardized psychometric tests. Testing was conducted 1 to 2 days before, 7 to 10 days after, and 1 month after each operation. Twenty age-matched, healthy control subjects were given the same battery of tests at comparable times. Compared with healthy subjects, the patient group had significantly lower scores on 3 of 19 tests before, 10 of 19 tests 1 week after, and 5 of 19 tests 1 month after surgical intervention. The patient group had similar test performances before and 1 week after the operations and improved on 3 of 19 measures 1 month after the operations. Degrees of illness and cardiopulmonary bypass variables were significantly related to only a small subset of memory measures. Results of this study are consistent with previous reports that underscore the contribution of nonspecific aspects of surgical intervention to neuropsychologic dysfunction in the immediate postoperative period. We conclude that neither the illness nor the surgical variables are directly related to substantial variance in cognitive function after operations on the heart. PMID- 1405673 TI - Full-thickness dynamic cardiomyoplasty of the left ventricle with free revascularized latissimus dorsi myografts. An experimental feasibility study. AB - Dynamic cardiomyoplasty, with use of a free latissimus dorsi myograft revascularized by the internal thoracic artery and vein, was performed in eight dogs subjected to electrical preconditioning for 8 to 12 weeks (group I) and in six unconditioned dogs (group II). The procedure was performed after the resection of the anterior wall of the left ventricle. Cardiac output and left ventricular stroke work were augmented by 23.7% +/- 9.4% and 44.1% +/- 15.9% after graft pacing with 50 Hz burst stimulation at a 1:1 synchronization ratio, while left atrial pressure ranged from 8 to 12 mm Hg. Analysis of the left ventricular function curve showed that graft pacing at rates of 1:1, 2:1, and 3:1 augmented global left ventricular function. Hemodynamic benefit by continuous pacing at a 3:1 ratio was seen for 1.97 +/- 1.90 hours (0.5 to 6.1 hours) in group I until complications unrelated to the graft terminated the study, while it lasted for only 0.19 +/- 0.09 hour in group II. During the stimulation, the ratio of the lactate output to the oxygen consumption of the graft in group I, a possible indicator of metabolic shift, was significantly less than in group II, (0.46 +/- 0.58 and 6.34 +/- 1.73; p < 0.01). We conclude that free grafts of transformed latissimus dorsi muscle can augment global left ventricular performance, with a physiologic preload by oxidative metabolism, and provide a viable option in full-thickness dynamic cardiomyoplasty. PMID- 1405674 TI - Warm glutamate/aspartate-enriched blood cardioplegic solution for perioperative sudden death. AB - This report describes an initial experience applying warm glutamate/aspartate substrate-enriched blood cardioplegic solution to resuscitate hearts in 14 patients with witnessed perioperative arrest. Ten patients were in stable hemodynamic condition in the catheterization laboratory (n = 3) or intensive care unit when sudden irreversible fibrillation developed. It progressed to electromechanical arrest in six patients. In patients with preoperative or postoperative arrest, conventional cardiopulmonary resuscitation and defibrillation were unsuccessful and extracorporeal circulation was started 22 to 150 minutes after arrest. The left ventricle was vented, the aorta clamped, and warm (37 degrees C) aspartate/glutamate blood cardioplegic solution was given at a rate of 150 ml/min for 20 minutes. All bypass grafts were open with good flows in patients who had had coronary bypass, and coronary bypass was done in the three patients who had preoperative arrest. Eleven of 14 hearts resumed normal sinus rhythm after aortic unclamping, only two electrocardiographically proved infarctions occurred, and 13 patients had complete hemodynamic recovery with improved ejection fraction. Three patients died: one of progressive cardiogenic shock, another of mediastinitis, and the third of irreversible neurologic damage. Eleven patients were discharged from the hospital and are well after a follow-up period between 3 and 9 months. We conclude that witnessed perioperative arrest with intractable ventricular fibrillation should be treated aggressively by administering cardiopulmonary resuscitation during prompt transfer to the operating room for total vented bypass and delivery of warm substrate-enriched blood cardioplegic solution. This treatment may salvage hearts thought to be damaged irreversibly and may be a feasible approach to intractable witnessed cardiac arrest, provided cardiopulmonary resuscitation maintains satisfactory cerebral perfusion pressure. PMID- 1405675 TI - Effect of an oxygen-enriched solution and multiple dosing of antegrade crystalloid cardioplegic solution on myocardial metabolism during coronary artery bypass graft operations. AB - The metabolic effect of excessive oxygenation and frequency of administration of antegrade crystalloid cardioplegic solution was assessed in 33 patients undergoing routine coronary artery bypass graft operations. Four patient groups were designed in which the initial aortic root injection was 1000 ml and then 100 ml administered through the vein grafts after completion of each distal anastomosis. The groups were divided as follows: group 1, single dose, normally oxygenated cardioplegic solution infused via the aortic root; group 2, single dose, high oxygen content cardioplegic solution infused via the aortic root; group 3, normally oxygenated cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes; group 4, high oxygen content cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes. In all groups myocardial mean septal temperature showed an immediate fall to approximately 11 degrees C with the initial aortic root doses and then a gradual rewarming to approximately 20 degrees C during the crossclamp period (mean 58.6 minutes). Metabolic parameters measured or calculated from the coronary sinus effluent were myocardial oxygen extraction, lactate production, base deficit, inorganic phosphate, glucose, potassium, creatine kinase (total and myocardial band fraction), and catecholamine production. There was no statistically significant difference in any of these determinations between each patient group. Furthermore, myocardial recovery, myocardial performance, and postoperative recovery characteristics were not different. We conclude that single or multidose aortic root crystalloid cardioplegic solution (either oxygen enriched or normally oxygenated) is equally effective in routine coronary artery bypass graft operations when septal temperatures are maintained between 15 degrees and 21 degrees C for a total arrest time of 60 minutes or less. In this study, increasing the volume cardioplegic solution given in multiple doses appeared to offer no significant metabolic or functional advantage in patients without complications who had satisfactory left ventricular function. PMID- 1405676 TI - Assessment of regional and transmural myocardial perfusion by means of intraoperative myocardial contrast echocardiography during coronary artery bypass grafting. AB - By using intraoperative myocardial contrast echocardiography, we assessed regional myocardial perfusion and transmural blood flow distribution immediately after myocardial revascularization. A total of 62 revascularized myocardial areas were studied in 31 patients undergoing coronary artery bypass grafting. The revascularized areas were divided into three different areas: S area, supplied by significantly stenosed coronary arteries (43 areas); C area, supplied by coronary collateral situation associated with totally occluded coronary arteries (12 areas); MI area, preexisting transmural myocardial infarction (7 areas). Myocardial contrast echocardiography was obtained by direct injection of 2 ml of sonicated 5% human albumin into the saphenous vein grafts at rest and during atrial pacing. Each area was divided into two layers of endocardial and epicardial halves, and myocardial enhancement of peak intensity was measured for each half and endocardial/epicardial gray level ratio was calculated: (1) The peak intensity of myocardial enhancement in S area and C area was significantly higher than that in MI area at rest as well as during pacing after myocardial revascularization. There was no significant difference in the peak intensity between S area and C area both at rest and during pacing. In S area the peak intensity significantly increased during pacing (p < 0.01), whereas it did not change in C area and MI area. (2) S area demonstrated no significant change in endocardial/epicardial intensity ratio during pacing. In contrast, the ratio in C area significantly decreased during pacing. (3) In S area with preoperative percent increase of segmental wall thickening lower than 25%, there was a significant correlation (r = 0.84, p < 0.001) between the peak intensity of myocardial enhancement and the postoperative changes of percent increase of segmental wall thickening in the revascularized areas. Thus, immediately after myocardial revascularization, intraoperative myocardial contrast echocardiography could provide a quantitative assessment of regional myocardial perfusion as well as blood flow distribution in the areas with myocardial infarction and with coronary collateral situation and in the areas supplied by stenosed coronary arteries. PMID- 1405677 TI - Invited letter concerning: the influence of paracardiac structures and conditions on cardiac performance in the postcardiotomy period. PMID- 1405678 TI - Rupture of the thoracic aorta: where is the expected improvement in surgical treatment? PMID- 1405680 TI - Hepatitis C--importance of screening the organ donor preoperatively. PMID- 1405679 TI - Invited letter concerning: right ventricular function after transatrial versus transventricular repair of tetralogy of Fallot. PMID- 1405681 TI - Invited letter concerning: the effect of extraanatomic bypass on aortic input impedance studied in open chest dogs: should the vascular prosthesis be compliant to unload the left ventricle? PMID- 1405682 TI - Physiologic assessment and surgical management of diffuse esophageal spasm. AB - The physiologic abnormalities and management of patients with diffuse esophageal spasm are controversial. We evaluated the symptomatic and functional results of surgical therapy in 19 patients with diffuse esophageal spasm who were incapacitated with dysphagia and chest pain and unresponsive to conservative management. A long esophageal myotomy with an antireflux procedure was performed in 15 patients, and four patients with multiple previous esophageal procedures had an esophagectomy. Eleven patients had increased esophageal exposure to gastric juice on preoperative 24-hour esophageal pH monitoring. The severity of dysphagia, chest pain, regurgitation, and heartburn was scored on a scale of 0 to 3 before and a mean of 24 months (range 8 months to 13 years) after the operation. After myotomy, each of these symptoms and the overall symptom score improved significantly (p < 0.01). The improvement in the symptom scores in the patients who had esophagectomy were comparable with the improvement after myotomy. On self-assessment, 90% of the patients would have the operation again if again faced with the decision. Standard and ambulatory 24-hour manometry showed a significant reduction in the amplitude of the esophageal body contractions, a decrease in the frequency of simultaneous contractions, and the elimination of multi-peaked waves after the myotomy. Despite the addition of an antireflux procedure, lower esophageal sphincter pressure, overall length, and abdominal length were reduced markedly after the myotomy. This was associated with persistent or emerging heartburn or regurgitation in four patients. These data indicate that a long esophageal myotomy is a valid treatment alternative in appropriately selected patients with diffuse esophageal spasm. Esophagectomy and colon interposition is the procedure of choice in patients with multiple previously failed myotomies. PMID- 1405683 TI - Plasma cell granuloma of the lung. AB - Plasma cell granuloma is an uncommon, nonneoplastic pulmonary lesion. An 11-year retrospective review of resected pulmonary tumors yielded six patients with plasma cell granulomas. Fine needle aspiration biopsy results were falsely positive for carcinoma in one patient. Adherence or invasion of the mediastinum was present in three patients. Granuloma in one patient, who underwent two operative procedures, was deemed unresectable at the initial thoracotomy. For both diagnostic and therapeutic reasons, early surgical excision is recommended for plasma cell granulomas of the lung. PMID- 1405684 TI - Surgical treatment of pulmonary metastases from uterine cervical cancer. Operation method by lung tumor size. AB - Between 1959 and 1986, 32 patients with pulmonary metastatic tumors from squamous cell carcinoma of the uterine cervix underwent pulmonary resection. The method of pulmonary resection was correlated with the pathology of the metastases. In 20 patients with pulmonary metastatic lesions 3 cm in diameter or larger, secondary lymph node involvement was observed in 65% and microscopic satellite lesions around the main metastatic lesion were seen in 50%. On the other hand, in none of 12 patients having metastatic lesions smaller than 3 cm was there accompanying lymph node involvement, and microscopic satellite lesions were observed in only one patient among them. Consequently, we concluded that wedge resection with a disease-free margin of 2 cm or a little more from the tumor edge was appropriate for lesions smaller than 3 cm in diameter, and lobectomy with lymph node dissection was necessary for lesions 3 cm in diameter or more. PMID- 1405685 TI - Tracheal sleeve resection for iatrogenic stenoses (subglottic laryngeal and tracheal). AB - Since 1975 200 tracheal sleeve resections for iatrogenic tracheal and subglottic laryngeal stenoses have been performed in our institution. Preoperative Nd:YAG laser is of paramount help in opening the stenoses. Tracheography is usually performed to specify the length of the stenosis and the distance from the vocal cords. Operative procedures are described. One hundred seventy five (87.5%) patients are definitely cured, but in this group 16 patients required a Montgomery tube for 6 months to 1 year to recover a normal tracheal diameter. Two patients needed a second tracheal sleeve resection. Nine (4.5%) patients died, and 16 (8%) had recurrent stenoses. Stenoses in these patients were treated with use of a tracheostomy tube, a permanent Montgomery tube, or an endotracheal stent. Partial anterior cricoid resections performed in 21 patients have had the same results as those of the whole series. Twenty one laryngeal releases were performed and proved to be efficient and safe. In our experience complications can be avoided by good selection and preparation of the patients, accurate identification of the level and length of the stenosis, and meticulous technique. PMID- 1405687 TI - Desmoid tumors of the chest wall. A locally recurrent problem. AB - Desmoid tumors, in general, are known for their propensity to recur. To evaluate treatment and results, we reviewed the records of 32 patients admitted to our institution with a chest wall desmoid tumor from 1948 to 1988. There were 13 men and 19 women whose ages ranged from 12 to 67 years (median 36 years). Four patients had Gardner's syndrome. Treatment was wide resection. Median follow-up was 110 months. The overall 5-year survival was 93%; 5-year disease-free survival was 71%. The 5-year local recurrence rate was 29%. Since death from disease is uncommon after resection, but local recurrence is common, we recommend aggressive wide resection in patients who have desmoid tumors of the chest wall when seen initially. PMID- 1405686 TI - Effects of low-dose steroids on bronchial healing after sleeve resection. A clinical study. AB - We prospectively evaluated the effect of low-dose steroids after bronchial sleeve resection in 20 consecutive patients. Ten patients (group I) did not receive steroids. Ten patients (group II) received 10 mg of methylprednisolone intravenously intraoperatively and 10 mg intramuscularly every day for 10 days. In addition, group II patients received 250 mg of hydrocortisone succinate endobronchially before extubation and 5 mg of methylprednisolone daily in an aerosol solution. Bronchoscopy was performed in all patients before extubation, every day for 10 days, and 1 and 3 months after the operation. Bronchial healing was graded endoscopically from grade I (no edema, excellent healing) to grade V (dehiscence). In group I, three patients showed grade I, four had grade II, one indicated grade III, one revealed grade IV (granuloma), and one showed grade V (dehiscence) healing. Mean postoperative hospital stay was 9.7 days. In group II all 10 patients showed grade I healing. Mean postoperative hospital stay was 7.3 days. We conclude that low-dose steroids improve the postoperative course in patients undergoing bronchial sleeve resection. PMID- 1405688 TI - Bidirectional cavopulmonary anastomosis in patients under two years of age. AB - Between December 1986 and December 1990, a bidirectional cavopulmonary anastomosis was performed in 27 patients younger than 2 years of age, including 12 with heterotaxia syndrome. Age and weight of patients averaged 14.2 +/- 6.6 months and 8.1 +/- 2.2 kg, respectively. Eleven had pulmonary atresia and 16 had pulmonary stenosis. The main pulmonary artery was ligated in seven patients in the latter group (subsequently reopened in one) and left open in nine (subsequently ligated in two). There were four hospital deaths (15%). All patients were discharged with anticoagulant/antithrombotic therapy to be continued for 6 months. There were two late deaths before further operations (8.7%). Two patients, one with acquired massive pulmonary arteriovenous fistulas and one with progressive common atrioventricular valve regurgitation, subsequently underwent definitive repair (biventricular in one), and both died. Heterotaxia syndrome (p = 0.087) and preoperative mean pulmonary artery pressure higher than 15 mm Hg (p = 0.09) were the only risk factors for overall mortality. PMID- 1405689 TI - Midterm results with cryopreserved allograft valved conduits from the right ventricle to the pulmonary arteries. AB - From 1985 to 1990, 89 patients underwent placement of 41 aortic and 54 pulmonic cryopreserved allograft valved conduits between the right ventricle and the pulmonary arteries. Six patients underwent replacement with a second allograft conduit. Median age at operation was 4.3 years, and 20 patients were infants less than 1 year of age. Conduit sizes averaged 11 mm in the conduits placed in 20 infants and 20 mm in the 75 placed in patients more than 1 year of age. There were 7 early deaths in 89 patients (7.8%, 70% confidence levels 5.4% to 11.3%) and 9 late deaths in 82 hospital survivors (11%, 70% confidence levels 8% to 15%). Actuarial survival was 81% (70% confidence levels 75% to 86%) at 33 months, and no deaths were due to conduit problems. Late reoperation was required in 13 patients (7 for conduit obstruction, 1 for conduit valve insufficiency, and 5 for nonconduit-related problems). Six of the eight reoperations were done in patients who had small (< or = 13 mm) conduits placed during infancy. Conduit failure was similar between pulmonic and aortic allografts. There were no deaths in the eight patients who required conduit reoperation. Actuarial freedom from reoperation for conduit dysfunction was 80.5% (70% confidence levels 72% to 86%) at 53 months for the entire group and 94% (confidence levels 88% to 97%) at 44 months for patients more than 1 year of age. Cryopreserved allograft conduits have good early and midterm results and are comparable to porcine xenograft conduits. Despite a likely need for replacement within 3 years, we continue to favor the use in infants of an allograft valved conduit over a xenograft Dacron conduit. The need to replace a cryopreserved allograft conduit appears similar for conduits of aortic or pulmonic origin. PMID- 1405690 TI - Evaluation of right ventricular function by regional wall motion analysis in patients after correction of tetralogy of Fallot. Comparison of transventricular and nontransventricular repairs. AB - Right ventricular function was assessed by regional wall motion analysis and by global function in 62 patients after repair for tetralogy of Fallot. Its relation to surgical procedures, with special attention to right ventriculotomy, was investigated. Patients were classified as follows: group Ia (n = 17), transpulmonary-transatrial repair without right ventriculotomy; group Ib (n = 22), transpulmonary-transatrial repair with minimal right ventriculotomy and small transannular patch; and group II (n = 23), transventricular repair with or without transannular patch. For regional wall motion analysis, fractional area change was used for three anterior parts obtained from hemiaxis area analysis of the lateral right ventriculogram. Ejection fractions were used for global right ventricular function. Functional assessment was done both at rest and during isoproterenol infusion, which is a stress test to evaluate cardiac functional reserve. At rest, group Ia showed better right ventricular anterior wall motion as well as global ejection fraction than did group II. Group Ib showed a global ejection fraction comparable to group Ia, with better regional wall motion in the middle anterior part of the right ventricle despite the depressed upper and lower anterior parts of the right ventricle. Group II showed depressed wall motion of the middle anterior part and the resultant impaired global ejection fraction. During isoproterenol infusion, group Ia showed significant increase in fractional area change of all anterior parts and in global ejection fraction. Group Ib showed significant increases in fractional area change at the middle and lower parts and in global ejection fraction comparable with group Ia. Otherwise, group II showed no significant change in fractional area change, or in global ejection fraction, at the upper and middle parts. These results indicated that transpulmonary-transatrial repair for tetralogy of Fallot provided better postoperative global right ventricular function and its reserve, with less impaired regional wall motion, than did the transventricular repair. PMID- 1405691 TI - Aortic wall stress profile after repair of coarctation of the aorta. It is related to subsequent true aneurysm formation? AB - True aneurysm formation at the site of coarctation repair has been increasingly recognized after synthetic patch aortoplasty. A mathematical model was developed to determine the aortic wall stress profile after coarctation repair with this technique. METHODS: A two-dimensional nonlinear mathematical model and a three dimensional finite element model were developed for different physiologic, geometric, and materials properties variables, which were incorporated into an idealized coarctation repair. RESULTS: The models demonstrated that the major variable affecting stress levels in the aortic wall after coarctation repair was the patch geometry. If the patch was allowed to balloon out, the aortic wall stress increased out of proportion to the increase in aortic diameter because of nonlinear effects. The maximal aortic wall stress concentration occurred opposite the patch. Patch stiffness was also an important variable, with a lower stiffness (subclavian flap repair) leading to a higher aortic wall stress for the same patch geometry as a synthetic patch repair. Inferences: Development of true aneurysms after coarctation repair by synthetic patch aortoplasty is likely to result from excessive aortic wall stress due to patch geometry. PMID- 1405692 TI - Can we predict the long-term function of the subclavian flap angioplasty? AB - Neonatal operations have improved the prognosis for newborn children with aortic coarctation. The 30-day mortality of 123 neonates with isolated coarctation of the aorta collected from nine series was found to be 0.8%. The subclavian flap angioplasty was the most frequently used surgical procedure in this collected series. This technique is relatively new, however, and many questions have yet to be answered. In this study we have done subclavian flap repair in newborn pigs and followed them up to adult ages. The pigs were killed 28 or 44 weeks postoperatively, and the aortas were reexamined. All flaps had grown symmetrically in width and length and parallel to the growth of the descending thoracic aorta. The flaps were macroscopically intact. Signs of degenerative processes were not found. The wall thickness of the subclavian flap increased by growth of the individual fibroelastic lamellar units in the tunica media. This adaptation to the increased wall stress occurred early in life. The wall strength of the flap also increased by thickening of the intimal layer. We conclude that the subclavian flap is well suited to function as a part of the aorta in adult life. PMID- 1405693 TI - The recognition, identification of morphologic substrate, and treatment of subaortic stenosis after a Fontan operation. An analysis of twelve patients. AB - Twelve children were identified with subaortic stenosis after Fontan's operation. All had absent resting and isoproterenol-provoked pressure gradient before the Fontan procedure. Six had a univentricular heart of left ventricular morphology, three had a single ventricle of right ventricular morphology, one had tricuspid atresia with transposition of the great arteries, one had pulmonary atresia, intact ventricular septum, and hypoplastic right ventricle, and one had corrected transposition with hypoplastic systemic ventricle. The median interval between the Fontan operation and the recognition of subaortic stenosis was 2.5 years. Ten patients underwent surgical treatment after a prior Fontan operation: Five had myectomy and enlargement of ventricular septal defect with two operative deaths; two had placement of a valved conduit from the ventricular apex to the descending aorta, and both died postoperatively; two with single ventricle had subaortic myectomy, and one had enlargement of ventricular septal defect and pulmonary aortic connection. Complete heart block developed in only one patient. Postoperative testing with Doppler echocardiography with color flow imaging demonstrated good relief of subaortic stenosis. All six children who survived the operation are well 4 months to 4 years later. Subaortic stenosis is a progressive lesion that may develop after a Fontan operation. Its surgical treatment continues to carry a significant mortality. Myectomy and enlargement of ventricular septal defect achieve direct relief of the obstruction with minimal risk of heart block. PMID- 1405694 TI - Does Down syndrome affect prognosis of surgically managed atrioventricular canal defects? AB - The appropriateness of surgical correction of complete atrioventricular canal defect in patients with Down syndrome has been questioned on a cost-benefit basis. Our experience with nonselective correction of all patients with atrioventricular canal defects gave us the opportunity to evaluate the impact of Down syndrome on postoperative survival. Between January 1, 1975, and December 31, 1989, we operated on 94 patients with Down syndrome and on 127 genetically normal patients. One hundred thirty-four patients had partial or intermediate atrioventricular canal defect (28% Down patients) and 87 had complete atrioventricular canal defect (74% Down patients). Thirty-two patients died perioperatively and 10 patients died during the 15-year follow-up. The actuarial survival was 90% in the genetically normal patients and 57% in patients with Down syndrome (p < 0.0001). Nonetheless, when the confounding effects of pulmonary vascular resistance and the prevalence of more severe anatomic forms in patients with Down syndrome were eliminated with a multivariable analysis in the hazard domain, Down syndrome was not a significant independent incremental risk factor. This was verified by fitting parametric survival to actuarial survival graphically and by a testing of fit. Patients with Down syndrome underwent fewer reoperations and fared as well as or even better, on clinical and echocardiographic investigation, than their genetically normal counterparts. PMID- 1405695 TI - The conduction system in truncus arteriosus and its surgical significance. A study of five cases. AB - Atrioventricular block may occasionally occur after surgical correction of truncus arteriosus. We therefore studied the conduction system by means of serial sections in five cases of truncus (one after surgical intervention) to delineate the course of the conduction system and its relationship to the ventricular septal defect and the membranous septum. In general, the ventricular septal defect is in the anterior septum, confluent with the truncus, and the atrioventricular bundle is posterior and unrelated to the rim of the ventricular septal defect. In cases in which the ventricular septal defect is anterior and separated from the membranous septum by distinct muscle, the ventricular septal defect can be surgically closed without injury to the atrioventricular bundle. If the ventricular septal defect is related to the membranous septum, the atrioventricular bundle may be close to the ventricular septal defect and susceptible to surgical injury. If muscle separates the ventricular septal defect from the membranous septum, the branching bundle is close to the ventricular septal defect and also is susceptible to surgical injury. In one operated case there was partial dissolution of the left bundle branch, and the right bundle branch was involved in surgical closure of the defect. In summary, in truncus the conduction system varies in its course and is related to the location of the ventricular septal defect and its relationship to the membranous septum. The ventricular septal defect may be close to or related to the membranous septum, and the atrioventricular bundle and the beginning of the bundle branches may be vulnerable to surgical injury. PMID- 1405696 TI - Results of early repair of ventricular septal defect after an acute myocardial infarction. AB - A 10-year experience with early operation for postinfarction ventricular septal defect is reviewed. Twenty-two patients underwent surgical repair; operative mortality was 36% (< 30 days). The actuarial survival was 64% at 1 month, 59% at 1 year, and 47% at 5 years. Risk factors predictive of operative mortality were diabetes (p = 0.001), elevated preoperative right atrial pressure (p = 0.02), the absence of a preoperative intraaortic balloon pump (p = 0.006), and a short time interval between infarct and operation (p = 0.018). Long-term survival was adversely related to diabetes (p = 0.030), elevated preoperative right atrial pressure (p = 0.005), and, surprisingly, survival was better in patients with a greater extent of coronary artery disease (p = 0.023). There were 14 operative survivors (64%) and 11 long-term survivors (3 months to 10 years, mean 6.0 +/- 3.5 years). Six of eleven survivors were in functional New York Heart Association class I, one was in class II, and four were in class III. PMID- 1405697 TI - Impaired relaxation of the human mammary artery after temporary clamping. AB - Internal mammary artery specimens from 17 patients were each divided into three separate rings. One ring (control) remained in Krebs solution and the other two were clamped for 30 minutes with either a soft or hard jaw clamp. Isometric tensions were measured in an organ chamber by contracting the rings twice with a thromboxane A2 mimetic, U46619, and relaxing the rings first with the endothelium dependent agent acetylcholine followed by the endothelium-independent agent sodium nitroprusside. Endothelium-dependent maximal relaxation of the rings was impaired from control after both soft (20% versus 91%; p < 0.01) and hard (1% versus 91%; p < 0.01) jaw clamps were used. However, relaxation after use of hard jaw clamps was significantly less than after use of soft jaw clamps (1% versus 20%; p < 0.05). Endothelium-independent maximal relaxation was not impaired from control after soft jaw clamps (89% versus 97%) were applied but was significantly impaired after use of the hard jaw clamps compared with control (73% versus 97%; p < 0.01) and compared with soft jaw clamps (73% versus 89%; p < 0.05). Rings of internal mammary artery specimens from 10 patients from each experimental group were silver stained. The percentage of intact endothelial cells was significantly greater after soft jaw clamping than after hard jaw clamping (39% versus 15%; p < 0.02). These data suggest that soft jaw clamps significantly reduce the degree of vasoactive dysfunction compared with hard jaw clamps. In addition, soft jaw clamps produce fewer morphologic changes in the human mammary artery after temporary occlusion. PMID- 1405698 TI - Detrimental sequelae on the wall of the internal mammary artery caused by hydrostatic dilation with diluted papaverine solution. AB - We studied the effect of hydrostatic dilation of the internal mammary artery used for coronary revascularization in 10 patients (aged 45 to 79 years, median 63 years). Diluted papaverine solution was injected in the lumen of distal segments of the internal mammary artery, the musculophrenic artery, or the superior epigastric artery that had been obtained at operation; injection was followed by hydrostatic dilation not exceeding a sheer force of 50 gm. In 12 control patients (aged 42 to 76 years, median 64 years) in whom the internal mammary artery had also been harvested for elective myocardial revascularization, similar arterial segments were wrapped in sponges soaked in papaverine solution of the same dilution. In the nondilated group the median (with interquartile range) number of fenestrations in the internal elastic lamina increased from the elastic (21, 7) to the elastomuscular (41, 11) and muscular segments (89, 12) (elastic elastomuscular: p = 0.006; elastic-muscular: p = 0.006; elastomuscular-muscular: p = 0.003) (Wilcoxon signed-rank test). In none of the three histologic segments were full-thickness disruptions of the intima and disruptions of the internal elastic lamina seen. Similarly, in the dilated group the number of fenestrations in the internal elastic lamina increased from the elastic (25, 18) to the elastomuscular (43, 9) and muscular (100, 13) segments (p values 0.01, 0.01, and 0.006, respectively). In addition, in 20% of the elastic sections, in 17% of the elastomuscular sections, and in 35% of the muscular sections of the dilated group, disruptions of the intima and internal elastic lamina were seen. Comparison of the number of fenestrations in internal elastic lamina in the three histologic segments between the nondilated and dilated groups revealed a significantly greater value in the muscular segments of the latter group (p = 0.01) (Mann-Whitney U test). We concluded that (1) hydrostatic dilation of the internal mammary, musculophrenic, and superior epigastric arteries may have detrimental effects on the histologic characteristics of the intima and the internal elastic lamina and (2) the number of fenestrations in the internal elastic lamina of these arteries is related to the presence or absence of elastic lamellae in the media. PMID- 1405699 TI - Inhibition of human internal mammary artery contractions. An in vitro study of vasodilators. AB - The internal mammary artery is currently the preferred conduit for myocardial revascularization; however, perioperative vasospasm of the internal mammary artery may limit its use as a bypass graft. The ability of various vasodilators to inhibit internal mammary artery contraction was investigated with the use of discarded segments of human internal mammary artery not used in coronary artery bypass grafting. Ring segments of human internal mammary arteries were suspended on strain gauges in muscle baths containing 37 degrees C Krebs solution for measurement of isometric tension in vitro. Arterial contraction was stimulated by elevating the extracellular potassium concentration to 70 mmol/L or by exposure to a 10 mumol/L concentration of norepinephrine, and inhibition of contraction by vasodilators was measured. The order of potency to inhibit potassium-induced contraction was as follows: nifedipine > verapamil > nitroprusside > papaverine. At maximal effective doses, nifedipine, verapamil, and papaverine almost completely inhibited potassium-induced contraction, whereas nitroprusside inhibited contraction by only 55%. When norepinephrine was used to contract the arteries, a biphasic relaxation curve was seen with nifedipine, but not with other vasodilator drugs. The order of potency to inhibit norepinephrine-induced contraction was as follows: nifedipine > nitroprusside > verapamil > papaverine. Maximal inhibition of norepinephrine contraction by these vasodilators ranged from 68% to 95%. Nitroglycerin, isoproterenol, and adenosine produced little or no inhibition of internal mammary artery contraction caused by potassium or norepinephrine. Although nifedipine was the most potent vasodilator, papaverine produced the greatest maximal inhibition of both potassium- and norepinephrine induced contraction of human internal mammary artery. PMID- 1405700 TI - Synergism between infarct-borne left ventricular dysfunction and cardiomegaly in increasing the risk of coronary bypass surgery. AB - The effect of cardiomegaly on operative and late mortality in patients with left ventricular dysfunction undergoing coronary bypass operation was investigated. The study group consisted of 178 patients whose left ventricular ejection fraction was below 45% and who were operated on from 1978 through 1985. Forty five patients (group A) had severe left ventricular dysfunction (ejection fraction < 30%) and 133 (group B) had moderate dysfunction (30% > ejection fraction > 45%). Twenty-four of group A (53%) and 54 of group B (41%) patients had cardiomegaly (cardiothoracic ratio on chest x-ray films > 0.5). There were 10 (6%) hospital deaths, four in group A (9%) and six in group B (4.5%). All four deaths in group A and the six deaths in group B were patients who had cardiomegaly. Regardless of the severity of the left ventricular dysfunction, there was no operative death among patients with normal heart size (p < 0.001). Age over 65, bypass time longer than 2 hours, and incomplete revascularization emerged as risk factors. Follow-up ranged from 5 to 13 years (mean 7.8 years). Overall 5-year actuarial survival, including hospital mortality, was 80% +/- 3%. Reduced 5-year survival was observed in patients with cardiomegaly (67% +/- 5% versus 91% +/- 3%, p < 0.05). Five- and 10-year survival of patients from group A with cardiomegaly was 53% +/- 7% and 18% +/- 13%, respectively. PMID- 1405701 TI - Combined cardiac and abdominal aortic aneurysm operations. The dual operation on cardiopulmonary bypass. AB - Eight patients underwent both cardiac operation and repair of abdominal aortic aneurysm. All had respiratory impairment and significant impairment of left ventricular function, whereas six patients had severe diffuse distal coronary disease. In all patients the cardiac procedure was performed first, and the patients continued to receive cardiopulmonary bypass. Rewarming was not commenced until the abdominal repair was well under way, to protect the vital organs. There were no problems in weaning the patients from bypass, and six of the patients were extubated within 24 hours; one required ventilation for 36 hours. One patient died of colonic infarction complicated by kidney failure without being extubated. Another patient who was initially extubated in 11 hours required reintubation because of poor lung function and eventually died of multisystem organ failure caused by bilateral lower limb ischemia that persisted despite embolectomies. All survivors are well and in New York Heart Association functional class I or II between 3 and 18 months postoperatively. We conclude that for patients considered unfit for abdominal aortic aneurysm operations because of the nature of the cardiac disease, the combined operation with cardiopulmonary bypass is both safe and effective. PMID- 1405702 TI - The stretched ventricle. Myocardial creep and contractile dysfunction after acute nonischemic ventricular distention. AB - The hypothesis that nonischemic distention of the arrested, flaccid ventricle causes myocardial creep and reduces ventricular contractile force was tested in 16 sheep. Left ventricular volume was calculated from ultrasonic dimension transducers spanning left ventricular major and minor axes and left ventricular wall thickness. Changes in left ventricular volume were plotted against left ventricular pressure, with and without temporary occlusion of both venae cavae before and after nonischemic distention of the continuously perfused, flaccid nonbeating left ventricle arrested with oxygenated, normothermic blood-potassium perfusate. During 12 minutes of cardiac arrest, an apical balloon progressively distended the left ventricle to a peak pressure of 40 mm Hg in 11 sheep using a protocol designed to prevent subendocardial ischemia or mechanical injury. Coronary sinus lactate measurements and myocardial distribution of microspheres confirmed the absence of ischemia in 16 animals. In five control sheep the balloon was inserted but not inflated. Left ventricular volume at zero pressure increased from 5.9 +/- 3.5 to 9.5 +/- 4.4 ml (p < 0.05) after balloon inflation and did not change in the control animals. After maximum distention of the balloon, static left ventricular volumes at identical pressures were significantly greater. After passive distention, the slope of the end-systolic pressure-volume relationship, a measure of contractility, decreased significantly (p < 0.05) from 7.1 +/- 2.8 to 3.5 +/- 1.8 mm Hg/ml and did not change in the control group. Passive distention ("stretching") of the nonischemic flaccid left ventricle thus causes myocardial creep and reduces ventricular contractility. PMID- 1405703 TI - c-myc and c-myb expression in acute myelogenous leukemia. AB - Monoclonal antibodies and flow cytometry were used to detect the expression of c myc and c-myb in the bone marrow (BM) and peripheral blood (PB) cells of patients with acute myelogenous leukemia (AML). The expression of neither gene was correlated with the percent blast cells in the BM or PB nor was there a correlation between c-myc and c-myb expression. A wide range of expression of each gene was found within each FAB type of AML. Patients who had a high proportion of leukemia cells expressing c-myb were less likely to respond to remission induction therapy than patients in whom a low proportion of cells expressed c-myb. This association appears to reflect an inverse relationship between the proportion of cells expressing c-myb and the sensitivity of leukemia cells to the killing effects of chemotherapy in vivo. Treatment outcome was unrelated to c-myc expression. PMID- 1405704 TI - Prolongation by differentiation-stimulating factor/leukemia inhibitory factor of the survival time of mice implanted with mouse myeloid leukemia cells. AB - Mouse myeloid leukemic M1 cells can be induced to differentiate into macrophages by differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF). We examined the effect of D-factor on the survival times of syngeneic mice implanted with two different clones (T-22 and R-4) of M1 cells. D-factor induced differentiation and suppressed DNA synthesis of sensitive T-22 cells but not resistant R-4 cells in vitro. For in vivo experiments, we used recombinant mouse D-factor (rmD-factor) produced in mammalian cells, which is glycosylated and is more stable in vitro and in vivo than unglycosylated rmD-factor produced in Escherichia coli. Treatment with rmD-factor prolonged the survival times of mice implanted with T-22 cells but not R-4 cells. PMID- 1405706 TI - Bleeding complications and coagulopathy in acute leukaemia. AB - Factors and inhibitors of coagulation and fibrinolysis were investigated on admission in 57 patients with acute leukaemia and they were correlated to the occurrence of haemorrhage. Coagulation disturbances were found in 98%. Seventeen of the patients with haemorrhagic symptoms had major bleeding. Severe thrombocytopenia (< 20 x 10(9)/l) was found in 16%. Patients with major bleedings had significantly lower concentrations of prothrombin complex, fibrinogen, protein C and platelets. Low levels of antiplasmin and fibrinogen were characteristic of 'bleeders' with promyelocytic and lymphoblastic leukaemia. We found a positive correlation between vWF:Ag and leukaemic cell count especially in lymphoblastic leukaemia (ks = 0.72). Reduced levels of antithrombin indicated a poorer prognosis. PMID- 1405705 TI - Use of the polymerase chain reaction to detect hypermethylation in the calcitonin gene. A new, sensitive approach to monitor tumor cells in acute myelogenous leukemia. AB - Based on the recent observations that, in a majority of patients with acute leukemia, the 5' end of the calcitonin gene was hypermethylated and abnormal DNA fragments were observed following HpaII restriction digestion, we have developed a PCR-based method to sensitively detect this abnormal methylation of the calcitonin gene in AML. Applying the concept of competitive PCR, a semi quantitative correlation was obtained between the amount of hypermethylation and the amount of leukemic cells present. These results suggest that this method will be useful to monitor the amount of tumor cells in bone marrow from patients with AML. PMID- 1405707 TI - Successful treatment of two cases of myelodysplastic syndrome coexistent with chronic lymphocytic leukaemia with lymphoblastoid interferon. PMID- 1405708 TI - Role of interleukin 6 in the growth of myeloma-derived cell lines. AB - The role of interleukin 6 (IL-6) in the growth of five multiple myeloma-derived cell lines was characterized. The U266 and RPMI 8226 cell lines demonstrated increased DNA synthesis when cultured with exogenous IL-6, expressed IL-6 cell surface receptors (IL-6Rs) and expressed mRNA for IL-6R. However, these cells did not secrete detectable IL-6 protein, and a neutralizing antibody to IL-6 did not inhibit their growth. Three other myeloma-derived cell lines ARH-77, IM-9 and HS Sultan did not respond to exogenous IL-6, secrete IL-6 or express cell surface IL 6Rs. The IL-6 responsive cell lines bore late B-cell surface antigens (Ags), CD38 and PCA-1, whereas those lines which were non-IL-6 responsive strongly expressed B1 (CD20) and B4 (CD19) Ags, representing earlier stages in B-cell differentiation. Finally, the two IL-6 responsive cell lines did not express Epstein-Barr virus (EBV) proteins; in contrast, EBV encoded proteins typically expressed during latency could be detected in the three non-IL-6 responsive lines, confirming infection with virus. These studies clarify the heterogeneity observed in the myeloma cell line phenotype and biology and suggest that the U266 and RPMI 8226 cell lines, which express IL-6 cell surface receptors and are IL-6 responsive, may be useful for further study of IL-6 signal transduction in and related IL-6 mediated growth of myeloma in vivo. In contrast, those cell lines which are IL-6-independent provide a model for further study of EBV transformation and IL-6-dependent growth mechanisms in malignancy. PMID- 1405709 TI - Epidemiology of acute leukaemia in the Cape Province of South Africa. AB - Of 535 consecutive cases of acute leukaemia diagnosed in the Cape Province between 1978 and 1985, demographic data are incomplete in 75 black patients and they have had to be excluded from the spatial analysis. Of the remaining 460 cases, 223 (48.5%) occurred in white patients and 237 (51.5%) in those of mixed ancestry, classified as coloureds according to the Population Registration Act No. 30 of 1950. The average incidence was 2.12, 1.37 and 0.58/100,000 for whites, coloureds and blacks respectively. There was no temporal trend in the incidence of acute leukaemia between the three race groups. The median age for whites was 30 years and for the coloureds was 15 years, which is comparable to the 16 years for the black patients. The two-peak age distribution for leukaemia was seen in the white group, but was absent in the other two groups. This is accounted for by a different distribution in non-lymphoblastic as opposed to lymphoblastic subtypes. Furthermore, there was a disproportionately high frequency of acute progranulocytic leukaemia in the black patients, whereas the white and coloured groups were similar. There was a single, clearly defined macro-scale cluster restricted to white patients in Statistical Region 17 (SR-17). This exploratory study provides the first epidemiologic data for acute leukaemia in the Cape Province. It needs to be extended in order to verify these observations under more controlled circumstances and to seek evidence for some environmental factors that may account for the geographical cluster. PMID- 1405710 TI - Effects of interleukin 2 on engraftment following autologous bone marrow transplantation (ABMT) in dogs. AB - Beagle dogs were treated with recombinant human interleukin 2 (IL-2) 6 x 10(6) International Units (IU)/day for 7 consecutive days following conditioning with sublethal (200 cGy) or lethal (400 cGy) doses of high-dose rate whole body irradiation (WBI) and reconstitution with 2 x 10(8)/kg autologous bone marrow cells, in order to assess the effect of IL-2 on engraftment. Engraftment of dogs conditioned by lethal doses of WBI was not impaired following treatment with IL-2 6 x 10(6) IU/day. At an RIL-2 dose of 6 x 10(6) and 9 x 10(4) IU/day, enhanced engraftment of autologous bone marrow cells was observed in dogs irradiated with a sublethal WBI dose in comparison with controls not treated by IL-2(p < 0.05). We conclude that therapeutic doses of IL-2 may be safely utilized during hematopoietic reconstitution. Under certain conditions IL-2 may even enhance hematopoietic reconstitution following ABMT. PMID- 1405711 TI - In vitro purging of clonogenic leukemic cells from human bone marrow by heat: simulation experiments for autologous bone marrow transplantation. AB - In order to apply a simple purging method by heat to autologous bone marrow transplantation (ABMT), we have revaluated the ability to purge clonogenic leukemic cells from the simulated marrow mixture of normal marrow cells and leukemic cell lines (HL-60, Molt-3 and HEL) in vitro by heat, using two different clonogenic assays for normal granulocyte-macrophage progenitors (CFU-GM) and leukemic cell lines. It appeared that in vitro hyperthermia (42 degrees C for 120 min) is able to selectively remove clonogenic leukemic cells from simulated tumor cell-normal marrow mixtures even when leukemic cell concentrations are increased up to 3 x 10(6) cells/ml in vitro, and results in a 4-6 log destruction of clonogenic leukemic cells/ml according to a limiting dilution assay, while leaving half of normal CFU-GM surviving. The hyperthermic purging of clonogenic leukemic cells was not affected in the presence of normal marrow cells in vitro. This high level of clonogenic leukemic cell depletion by heat correlated with that of immunologic and pharmacologic studies. These results suggest that in vitro hyperthermia could be applied effectively and safely for the elimination of residual clonogenic leukemic cells in autologous marrow grafts before ABMT. PMID- 1405712 TI - Alcohol consumption and risk of leukemia, non-Hodgkin's lymphoma, and multiple myeloma. AB - Population-based case-control interview studies of white men, 578 with leukemia, 622 with non-Hodgkin's lymphoma, and 820 controls from Iowa and Minnesota and 173 with multiple myeloma and 452 controls from Iowa, offered the opportunity to investigate the relationship of these cancers with alcohol consumption. Although drinkers had non-significantly elevated risks for specific subtypes of leukemia (acute lymphocytic leukemia (OR = 3.0), myelodysplasia (OR = 1.6), and other leukemia (OR = 1.5)) and multiple myeloma (OR = 1.3), there were no statistically significant findings and no dose-response gradients with amount of alcohol consumed. Thus, these data suggest that alcohol is not an important contributor to the etiology of lymphatic and hematopoietic tumors. PMID- 1405713 TI - Influence of high versus low intestinal concentration of gram-negative bacteria and endotoxin on the susceptibility of murine myelopoiesis in bone marrow and spleen to cytostatic treatment with Ara-C. AB - The haematopoietic recovery after i.v. cytarabine was studied in C3H/Law mice as a measure for stem cell susceptibility in relation to the intestinal Gram negative bacteria (GNB) and endotoxin. Reduction or elevation of GNB and endotoxin was induced by either polymyxin or bacitracin, both non-absorbable antibiotics. Bacitracin caused less suppression of the splenic cellularity after cytarabine, and an advancement of the recovery of femoral nucleated cells. The femoral recovery of CFU-GM exhibited a biphasic pattern. The speed and height of the rebound increase of CFU-GMs were significantly affected by the antibiotics. Thus, (modulation of) the murine intestinal microflora influences the haematopoietic recovery after cytostatic drugs. The mechanisms involved are complex; intestinal endotoxin seems to play a role. PMID- 1405714 TI - Rapid production of diversity during the progression of a mixed lineage leukaemia. AB - A leukaemia presenting with two morphologically different blast populations failed to respond to either antimyeloid or antilymphoid treatment and showed a rapid clinical progression. Immunophenotyping provided good evidence for two blast populations, one lymphoid and the other lymphoid with granulocyte monocytic markers. Two different gene rearrangements within JH were also observed with band densities corresponding to the sizes of the two blast cell populations. A t(19; 22) translocation was observed in almost all cells at presentation one of which evolved into a subclone, becoming dominant in the terminal phase of the disease. We show here both the clonal evolution and clonal competition that occurred in this leukaemia and suggest that the potential of the tumour stem line for rapidly producing diversity was the reason for the resistance to treatment. PMID- 1405715 TI - Primary, single, autosomal trisomies associated with haematological disorders. United Kingdom Cancer Cytogenetics Group (UKCCG). AB - The United Kingdom Cancer Cytogenetics Group (UKCCG) collected retrospective data on 73 cases of acquired, single autosomal trisomies associated with haematological disorders, excluding trisomy 8 cases in myeloid conditions and trisomy 12 in lymphoid conditions. The bone marrow and/or blood smear morphology was reviewed in 49 cases. Trisomies for chromosomes 21, 11, 9 and 13 respectively were represented most frequently. Trisomy was not reported for chromosomes 1, 2, 5, 7, 16 or 17 and there was only one case of trisomy 8 in a non-myeloid condition and one case of trisomy 18. Of the 73 patients, 60 had myeloid disorders, 12 had lymphoid disorders and there was one case of acute undifferentiated leukaemia. There was no evidence of predisposing factors involved in the etiology of trisomy associated with haematological disorders. PMID- 1405716 TI - Flow cytometric analysis of cytokinetics of L3-acute lymphoblastic leukemia/lymphoma. AB - Cell kinetic differences have been described between acute lymphoblastic leukemia with L1 and L2 morphology. We now report cytokinetic and DNA ploidy findings of the rare L3 B-cell leukemia/lymphoma. Flow cytometry analysis of nineteen samples was performed by simultaneous DNA-RNA staining with acridine orange. RNA and DNA indices and cell cycle distributions were calculated. The RNA-index of the G0/G1 cells was 17.9 +/- 8.7 and the number of cells in S phase and S + G2M were 21 +/- 10.6 and 28.0 +/- 13.9 percent respectively. DNA aneuploidy was found in 6/19 (31.6%) and in two cases multiple aneuploid cell lines were observed. DNA aneuploidy and multiple abnormal stemlines adversely affected survival (p less than 0.05), while kinetic parameters did not affect survival (p greater than 0.05). The cytokinetic data are significantly different (S phase and RNA-I; p less than 0.001) than previously reported for the L1 and L2 ALL. Abnormal DNA stemlines were found in cases with no detected cytogenetic abnormalities. This study confirms that L3 ALL is characterized by significantly increased proliferation and provides a means for a flow cytometric identification of this subtype as compared to L1 and L2 ALL. PMID- 1405717 TI - Maturational stage specific immunoglobulin heavy chain gene rearrangements, determined by D and D upstream region gene structures. AB - In 43 cases of various B-cell lineage tumors, precise gene structures of rearranged immunoglobulin heavy chain (IgH) were studied. By Southern-blot analysis of D upstream (5'D) gene of IgH, biallelic rearrangement structures, D-J or V-D-J, were determined and consequently maturational stage specific IgH rearrangement patterns were investigated. B-precursor ALL cases (especially stage IV of Nadler's criteria) have V-D-J rearranged IgH genes on both alleles. In contrast, most of the mature B-cell malignancies, excluding multiple myeloma, have IgH genotype of D-J/V-D-J. In addition, in case of D-J/V-D-J, the D gene used in D-J joining has been speculated by Southern-blot of D genes. So, these approaches for inquiring precise structures of rearranged IgH genes are supposed to provide new information of lymphocyte differentiation and leukemogenesis. PMID- 1405718 TI - Relation of 5'-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia. AB - Ecto-5'-nucleotidase (ecto-5'NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5'NT (cyto-5'NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto 5'NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10- c mu- precursor B-ALL. CD10+ ALL cases with high ecto-5'NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5'NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5'NT and AP activities. We conclude that high ecto-5'NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5'NT and AP activities associated with 6-thiopurine resistance. PMID- 1405719 TI - Induction of permanent regression of Friend virus (FV) leukemia by adoptive transfer of T helper and not T cytotoxic cells. AB - Friend virus (FV) induces a progressive erythroleukemia that can be made to permanently regress by the transfer of in vitro cultured virus-specific T cells (CTL/RFB) without any other adjunctive treatment. To determine the role of T cells in regression, CTL/RFB were enriched for specific T-cell subsets by treatment with monoclonal anti-Lyt2.2 or anti-L3T4 antibody and complement (C'). Pre-treatment of CTL/RFB with anti-Lyt2 antibody and C' did not affect permanent regression incidence, while CTL/RFB depleted of L3T4+ cells induced temporary regressions with all mice recurring. The number of splenic Lyt2+ (CD8+ equivalent) cells was constant irrespective of the leukemic status of the animals. However, the number of L3T4+ cells (CD4+ equivalent) in leukemic mice was three-fold lower than that of normal mice with regressed mice demonstrating a 30% increase in the number of L3T4+ cells compared to normals. Spleen cells from leukemic animals were also unable to produce IL-2 in response to mitogen stimulation. These results indicate that L3T4+ cells are involved in regression of erythroleukemia. PMID- 1405720 TI - Production of a negative regulator of IL-3 by bone marrow cells in response to the supernatant of IL-3-producing STIL-3 leukemia cells. AB - When spleen cells of mice grafted with STIL-3 C5 cells, a leukemic T-cell line producing IL-3, are cultured in vitro, a high IL-3 activity is detectable in the culture supernatant. However, when bone marrow cells of the same grafted mice are cultured under similar conditions, hardly any IL-3 activity is detectable. To elucidate the mechanism of this difference, we examined whether the bone marrow cells either suppress IL-3 production by STIL-3 C5 cells or produce an IL-3 inhibitor. When STIL-3 C5 cells were cultured in the presence of normal bone marrow cells, the culture supernatant showed a significantly reduced IL-3 activity as assessed by growth stimulatory effects on IL-3-dependent DA-1 cells and mast cells. The conditioned medium (CM) did not inhibit the growth of IL-3 independent cell lines. Heat treatment of the CM resulted in a recovery of the IL 3 activity, indicating that the effect was mediated by a heat-labile inhibitor rather than by suppression of IL-3 production. CM of bone marrow cells alone did not inhibit the IL-3 activity. The inhibitor was produced by a stem cell-enriched fraction of the bone marrow, and not by fractions of T cells, granulocytes, or adherent cells including macrophages. Stimulation of the stem cell-enriched fraction of bone marrow with STIL-3 C5-CM also induced the production of the IL-3 inhibitor, which was recovered in a MW 50-100 kD fraction after ultrafiltration. These results suggest a possible presence of a feedback mechanism against the IL 3 effect on hemopoietic stem cells and progenitors in the bone marrow. PMID- 1405721 TI - Analysis of chronic lymphoid leukaemias according to FAB. AB - We have studied the immunophenotypic features in patients with chronic lymphoid leukaemia and investigated the suitability of classification according to guidelines of the French-American-British (FAB) group. Immunophenotyping was carried out on cytocentrifuge preparations of mononuclear blood leukocytes using the alkaline phosphatase-antialkaline phosphatase (APAAP) method. The 114 leukaemias, including 58 cases of B-chronic lymphocytic leukaemia (B-CLL), 3 Waldenstrom's macroglobulinaemia, 6 prolymphocytic leukaemia (B-PL), 13 B-CLL/PL, 4 B-CLL of mixed cell type, 8 splenic lymphoma with villous lymphocytes (SLVL), 8 hairy cell leukaemia (HCL), two HCL variant, three leukaemic phase of follicular lymphoma, two leukaemic phase of intermediate lymphoma, two plasma cell leukaemia and two chronic T-cell leukaemia, were investigated. The 111 of 112 B-chronic lymphoid leukaemias (B-CLL + B-PL + B-CLL/PL + SLVL + HCL etc.) showed monotypic light chains. The antibody HML1 was highly specific for HCL. The antibodies CD11c and CD25 were positive in all HCL cases, but were not specific for this disease. CD5 positivity and CD22s negativity were found in most patients with B-CLL, B CLL/PL and B-CLL of mixed type. This marker type has a limited value for differentiation from the other chronic lymphoid leukaemias. We also studied three patients with chronic lymphoid leukaemia which were not described by the FAB classification. We conclude that a study of the morphology of the leukaemic cells was the most useful basis for the diagnosis of these leukaemias, whereas immunotyping was apparently valuable only in individual cases. PMID- 1405722 TI - The effects of microtubule disrupting drugs on the differentiation of HL-60 leukemia cells. AB - We and others have previously shown that microtubules (MT) are stained more intensely and are organized differently in differentiating leukemia cells. To study the effects of the MT disrupting drugs, colchicine (Coln) and vincristine (VCR), on the maturation process, HL-60 leukemia cells were pretreated with Coln or VCR for 1 h and then exposed to either retinoic acid (RA) or dimethyl sulfoxide (DMSO). Neither Coln nor VCR induced the differentiation of HL-60 cells, but in combination with RA increased the percentage of nitroblue tetrazolium-positive cells, the expression of the mature myelocyte surface marker Mo 1, and the content of MT over the effects produced by RA alone. In contrast, pretreatment with Coln or VCR delayed the commitment to a differentiation pathway induced by DMSO. The supra-additivity exhibited between Coln and RA required the administration of Coln prior to RA; thus, Coln had no effect when given two days after the cellular exposure to RA. The findings suggest that (a) a combination of non-cytotoxic concentrations of Coln or VCR with RA may have clinical utility as inducers of leukemia cell maturation, and (b) MT may be involved in modulating signal transduction during the initiation of HL-60 cell differentiation. PMID- 1405723 TI - No correlation between site of breakpoint in the BCR gene and platelet counts in Philadelphia chromosome-positive CML. AB - In chronic myelogenous leukemia (CML) malignant cells are characterised by the Philadelphia chromosome (Ph), resulting from a translocation t(9;22). The position of the breakpoint within the major breakpoint cluster region (M-bcr) on chromosome 22 has been shown to correlate with the clinical course of the disease or, more recently, thrombopoietic activity. We have therefore determined the breakpoint localisation in 53 Ph-positive CML patients. Following the 5'/3' region definition of Inokuchi et al. Leukemia Research 15, 1067 (1991) [1], 22 of our patients have 5' and 31 of our patients have 3' orientated breaks. No correlation was found between platelet counts and breakpoint localisation. PMID- 1405724 TI - Molecular analysis of a HTLV-IpX defective human adult T-cell leukemia. AB - Fresh and cultured leukemia cells from an adult T-cell leukemia (ATL) patient which possessed gag and env gene defective human T-cell leukemia virus type I (HTLV-I) provirus genome were molecularly analyzed. Cells from both fresh and the established cell line, named KB-1 showed identical surface markers of helper T cells, expressed the interleukin 2 (IL-2) receptor and had an identical defective HTLV-I provirus genome with deletions of the gag and env genes involving pX gene exon 2. The KB-1 cells grew vigorously in vitro, even in the absence of IL-2 and the culture supernatant of KB-1 contained a large amount of IL-2. Neither pX mRNA nor p40(TAX) protein was detected in the KB-1 cells. The collective evidence suggests that the pX gene was not functioning in this particular ATL case. The biological function of the HTLV-I genes, especially the pX gene is discussed in relation to the early and late leukemogenesis of ATL. PMID- 1405725 TI - Chronic myelocytic leukemia with myeloblastoma has higher frequency of ras oncogene mutation. PMID- 1405726 TI - Electron microscopical demonstration of horseradish peroxidase by use of tetramethylbenzidine as chromogen and sodium tungstate as stabilizer (TMB-ST method): a tracing method with high sensitivity and well preserved ultrastructural tissue. AB - Until now methods using tetramethylbenzidine (TMB) for electron microscopy (TMB EM methods) are all unable to provide a maximum demonstration of transported horseradish peroxidase (HRP) while maintaining good ultrastructural tissue preservation. In order to solve this problem, we have attempted to adapt a newly developed, highly sensitive TMB method using sodium tungstate (ST) as the stabilizer (TMB-ST method) for HRP electron microscopic retrograde and anterograde fiber tracing. The present study shows that the TMB-ST method combined with diaminobenzidine-cobalt (DAB-Co) is more sensitive than existing TMB-EM methods and that ultrastructural details are well preserved with this combined method. The resultant reaction product complex after osmication is stable and is observed as characteristic crystal-like structures which are extremely electron dense and often aggregated into clumps. In contrast, the TMB ST method without the DAB-Co step frequently produces a moderate electron-dense reaction product. Therefore, we recommend the TMB-ST method combined with DAB-Co for HRP electron microscopy. PMID- 1405727 TI - Open fetal spinal cord surgery in rats with low mortality achieved by prevention of oligohydramnios. AB - Myelotomies were performed with an open microsurgical technique in rat fetuses aged between E16 and E18. In 87 consecutively treated fetuses the net surgical mortality was as low as 7%. The cause of death due to fetal surgery is shown to be amniotic fluid loss. The high survival rate is attributed to the prevention of oligohydramnios. The technique is described in detail and the results are discussed. PMID- 1405728 TI - A non-surgical technique for accurate intracerebral injections in rat. AB - An improved technique for intracerebral injection into rats is described. This technique uses a metallic skull template as an injection aid, aligned with the maxillary incisors, the eyes and the outer ear canals of anesthesized animals. With this device we have been able to target brain structures as small as 4 mm3 both rapidly, accurately and reproducibly. The new method provides a useful alternative to common stereotaxic techniques for rats up to 300 g. PMID- 1405730 TI - An in vitro preparation of the mudpuppy for simultaneous intracellular and electromyographic recording during locomotion. AB - In this report we describe the development of an in vitro preparation of the mudpuppy (Necturus maculatus) used to investigate locomotion in walking vertebrates. The preparation consists of the first 5 segments of the cervical spinal cord and the attached forelimb. The preparation is bathed in a cooled (15 degrees C) and oxygenated spinal cord Ringers solution and remains viable for 36 100 h. Locomotion can be elicited during the first 36-48 h by applying the excitatory amino acid N-methyl D-aspartate (NMDA) to the bath. Cutaneous and dorsal root reflexes remain unchanged for much longer periods of time (72-100 h). During locomotion, intracellular recordings can be made from interneurons and motoneurons while simultaneous electromyographic (EMG) recordings are made from forelimb muscles. Rhythmically active interneurons can be classified according to their phase of activity during the step cycle. Further classification of interneurons involves both monitoring the afferent input to these cells from dorsal root and cutaneous afferents as well as using their action potentials as a trigger for averaging the ongoing locomotor EMG activity. In this way some of the input and output characteristics of the interneurons can be monitored. The ability to record simultaneously from interneurons and muscles offers distinct advantages over current in vitro preparations. PMID- 1405729 TI - Combining in vivo volume-controlled pressure microejection with extracellular unit recording. AB - We report a method for combining extracellular single-unit recording with pressure ejection, permitting microvolume quantification through the measurement of meniscus movement. Good optimization of both high quality recording and precise determination (in the nanoliter range) of the pressure-ejected volume can be obtained by using a recording electrode affixed to a calibrated, narrow inner diameter ejection pipette. PMID- 1405731 TI - An empirical test for the reliability of quantal analysis based on Pascal statistics. AB - We have previously shown that amplitude distributions of excitatory postsynaptic potentials (EPSPs) can be better described by Pascal distribution when the mean quantal content (m) is not stationary but fluctuating according to gamma distribution. We have developed the procedure of estimating quantal parameters by the method of maximum likelihood. In this study, we examined empirically the reliability of this quantal parameter estimation procedure by using Monte Carlo simulations. The reliability was evaluated by absolute values of error (magnitude of error) of estimated parameters relative to the known 'true' parameters. The mean values of relative magnitude of error were relatively small unless the probability of failures was too large (greater than 0.7) or too small (less than 0.1). The values of relative magnitude of error became smaller in association with increases in the sample size. When the probability of failure was between 0.1 and 0.7, the sample size was 1000, coefficient of variation of quantal size was 0.45, the values of relative magnitude of error of estimated parameters were below 0.1. These results mean that this procedure gives relatively reliable estimates of quantal parameters with the limitation that the probability of failure is neither too large (greater than 0.7) nor too small (less than 0.1); it is preferable that the sample size is as large as 1000. PMID- 1405732 TI - A simplified approach to retrograde/anterograde axonal labeling using combined injections of horseradish peroxidase and ibotenic acid. AB - Combined injections of ibotenic acid and horseradish peroxidase (HRP) were made into the region of the mouse ventrobasal thalamus that is related to the large mystacial vibrissae. Examination 4 and 5 days later of the corresponding area of the primary somatosensory cortex (i.e., barrel cortex), in thick and in thin sections, showed it to contain numerous corticothalamic projection cells the somata, dendrites and axons of which were densely labeled by the retrograde transport of HRP. Analysis of serial thin sections showed that thalamocortical axon terminals, which had degenerated in response to the injection of ibotenic acid, formed approximately 20% of the asymmetrical synapses in barrel cortex. The fine structure and distribution in cortex of degenerating thalamocortical axon terminals and of intrinsic HRP-labeled corticothalamic axon terminals were identical to those reported in previous studies in which the injection of HRP into the thalamus was combined with the making of electrolytic lesions. This indicates that injecting ibotenic acid is an effective replacement for electrolytic lesioning of the thalamus. The combined injection of ibotenic acid and HRP represents a new and efficient approach for studying reciprocal projection pathways. PMID- 1405733 TI - Brain tissue slice thickness monitored by ion-profile measurement. AB - The thickness of a brain tissue slice preparation governs the amount of time required for substances to diffuse from the bathing solution to preparation. Slice thickness may increase during the experiment, e.g., in cases of hypoxia where osmotic pressure within the tissue changes, enabling water to enter the preparation. With increasing slice thickness diffusion paths from the bath to central layers of the preparation increase possibly resulting in an insufficient O2 supply to central layers. Therefore, the actual slice thickness should be monitored during the experiment especially in cases where osmolarity is changed or during hypoxia. This paper describes a simple method to monitor the actual slice thickness using ion profiles measured by ion selective micro-electrodes driven at a constant rate of approximately 10 microns/s (sample rate ca. 10/s). The method is based on steep changes in the concentration gradients at the upper and lower surfaces of the preparation induced by simple diffusion in the presence of concentration gradients between the non-tortuous bath and the tortuous tissue. The thickness of the preparation is derived from the location of the steep gradient changes as reflected by the registered profile. PMID- 1405734 TI - Polyacrylamide as an infiltrating and embedding medium for vibratome sectioning of human fetal cerebellum containing DiI-filled axons. AB - Polyacrylamide is widely used for the separation of proteins by electrophoresis. Here the usage of polyacrylamide as an infiltrating and embedding medium for vibratome sectioning of human fetal cerebellum containing DiI-filled axons is reported. The procedure is simple to implement and has several advantages: it does not require prior dehydration and clearing of tissue; it can be carried out at a low temperature of 4 degrees C; and the polyacrylamide neither dissolves the DiI nor does it interfere with the visualizing of DiI-filled profiles under fluorescence microscope. PMID- 1405735 TI - The use of naloxone to facilitate the generation of the locomotor rhythm in spinal cats. AB - The locomotor rhythm evoked by perineal stimulation in clonidine-treated acute and chronic spinal cats can be produced more easily when the opioid receptor antagonist naloxone is also administered. Naloxone increases the frequency of the locomotor rhythm and decreases the intensity of skin stimulation required for evoking the rhythm. A useful property of naloxone is that it can restore the locomotor rhythm when the rhythm wanes, thus prolonging the time period over which locomotor activity can be generated. Administration of naloxone without clonidine does not enable the locomotor rhythm to be generated by skin stimulation, but it does reduce the concentration of clonidine required for the expression of a robust rhythm and may increase the chance of a successful preparation. We conclude that naloxone is a useful pharmacological tool for studies on the locomotor pattern generator. PMID- 1405736 TI - Separation of synaptic and spike activity in intracellular recordings for selective analysis. AB - A software spike filter has been developed which allows the separation of synaptic activity and action potentials in intracellular recordings. The algorithm uses the different velocities of the membrane potential during synaptic and spike activity and a time window to identify action potentials. When spikes are recognized, they are removed and the membrane potential is substituted by interpolated values. The spike filter makes possible a separate quantitative evaluation of postsynaptic potentials and spike activity. Thus a comprehensive characterization of neuron activity can be obtained. The spike filter is part of a modular software package designed for the evaluation of neurobiological data. PMID- 1405737 TI - Model invariant method for extracting single-channel mean open and closed times from heterogeneous multichannel records. AB - We present a proof that the mean open (and closed) times of the individual channels in a multichannel record can be found in a model-independent fashion. As the results are model independent, they can be derived by assuming the simplest model for all the channels, namely that they all have the basic CLOSED in equilibrium with OPEN scheme. In particular, the method can be applied to patches where the channel population is heterogenous with respect to open probability. Multichannel simulations are performed to test the limits of applicability of this method to restricted amounts of data. One conclusion is that increasing the number of channels does not substantially reduce the errors in estimating the mean times, in spite of the 'increased information' present. We also prove the general applicability of the algorithm of Fenwick et al. (1982) in estimating the mean times without knowledge of the number of channels present, and discuss its limitations. An illustration using experimental data is also given. PMID- 1405738 TI - Continuous scan cyclic voltammetry (CSCV): a new high-speed electrochemical method for monitoring neuronal dopamine release. AB - This report describes a new form of fast cyclic voltammetry which samples electrochemical reactions of dopamine at one every 10 ms. We have called this technique 'continuous scan cyclic voltammetry' (CSCV). The technique uses a carbon fibre microelectrode which is connected to a continuously active sine-wave source. The applied voltage is a 100 Hz precision sine wave. Faradaic signals due to cycles of continuous oxidation and reduction of dopamine at the tip of the electrode can be observed superimposed on a fixed charging current. The technique is insensitive to moderate concentrations of ascorbate as a depletion zone for ascorbate is rapidly established around the electrode. In a brain slice preparation the technique can show the time course of dopamine release on a millisecond time scale. It should prove a valuable new tool for the investigation of dopamine transmission in the brain. PMID- 1405740 TI - Extracellular perfusion controller for electrophysiology. AB - This paper describes the design and utility of a perfusion controller to facilitate the handling of multiple extracellular solutions. The controller consists of an interface box with both manual and computer controls and a set of solenoid valves. This provides remote handling of the switching of multiple solutions into an experimental chamber. It is described how this system can be used in whole-cell patch-clamp experiments to measure various ion channel currents as well as Na/K pump currents. Other possible uses are discussed along with suggestions for interfacing the perfusion controller with existing perfusion systems. PMID- 1405739 TI - Intracellular recording from dopamine neurons in the substantia nigra: double labelling for identification of projection site and morphological features. AB - We have adapted an intracellular recording technique that allows differentiation of dopamine neurons in vitro based on their projection sites and morphology. We pre-labelled 'nigrostriatal' dopamine neurons in vivo by stereotaxically injecting rhodamine-labelled microspheres (RFM) into the dorsal striatum. Following slice preparation, dense neuronal labelling with RFM was observed in the medial two-thirds of the substantia nigra zona compacta. The visible neurons in the superficial layers were not viable; consequently, we recorded from dopamine neurons that were located directly below the clusters of fluorescent neurons. Each recorded neuron was subsequently filled with N-(2-aminoethyl) biotinamide (1) to confirm whether it projected to the dorsal striatum (by presence of both RFM and biotinamide) and (2) to examine its morphological features. Four of 7 dopamine neurons successfully recovered were double labelled and exhibited multipolar cell bodies with dendrites projecting into the zona reticulata. No differences in the resting membrane potential, spontaneous activity, or membrane response to constant current injections were observed between the confirmed nigrostriatal dopamine neurons and the others. Our technique should allow pharmacological manipulations of selective dopamine pathways in vitro and help in elucidating various factors responsible for differential regulation of populations of dopamine neurons. PMID- 1405742 TI - Construction of a microdialysis probe with attached microinjection catheter. AB - We describe a microdialysis probe with attached side catheter for making submicroliter injections at the site of the probe in the awake, freely moving rat. This design allows the local application of drugs which cannot be applied in the perfusion medium either because of their inability to pass through the dialysis membrane or because of their interference with chromatographic detection of compounds of interest. PMID- 1405741 TI - The playground maze: a new method for measuring directed exploration in the rat. AB - A new test, called the 'playground maze', is described. Rat exploratory responses to a single novel object are measured in the context of responses to 7 familiar objects in a familiar environment. Responses are measured as time spent in areas around the objects on a circular open field. These times are expressed as percentages of the total time spent exploring all the objects and a value which is significantly greater than the expected chance level (12.5%) indicates a novelty response. The paths traversed by the animals on the maze are also recorded and the lengths of these give a measure of locomotion. Preliminary experiments on the effects of chlordiazepoxide (CDP) (1-5 mg/kg) and amphetamine (1.5-4 mg/kg) are reported. CDP significantly increased the novelty response but had no effect on locomotion. Amphetamine treatment at 4 mg/kg abolished the response to novel objects while lower doses (1.5 and 2 mg/kg) did not affect it. All 3 doses of amphetamine significantly increased locomotion. This test provides a new way of measuring the exploratory response to novelty under low stress conditions and allows the separation of drug effects on directed exploration and locomotion. PMID- 1405743 TI - Quantitative analysis of reflex responses in the averaged surface electromyogram. AB - The relationship between the averaged surface electromyogram (EMG) and the activity of motoneurones in reflex studies is analysed mathematically. This analysis reveals that, subject to certain conditions being met, the integral of the average of the unrectified EMG is linearly related to the activity of motor units in the muscle. This was tested with experimental data. The activity of 2 motor units, and the surface EMG, were recorded directly in a reflex paradigm. A close match was found between the integral of the average of the unrectified EMG and the summed peristimulus time histograms (PSTHs) of the units' activity. This analysis gives more quantitative measurements of the timing of motoneuronal activity in reflexes than the conventional analysis of the EMG. It also offers the potential for making quantitative measurements of changes in motor unit activity evoked by different stimuli. This analysis avoids the pitfall of the artefactual peaks that can occur in the average of the rectified EMG as a consequence of the full-wave rectification. It is concluded that the integral of the unrectified average offers a valuable adjunct to the conventional analysis in many reflex studies. The analysis can also be applied to quantitative studies of neurograms. PMID- 1405744 TI - Monitoring neuronal activity during discrete behaviors: a crawling, swimming and shortening device for tethered leeches. AB - An apparatus is described which facilities continuous electrophysiological recordings in segmental ganglia of leeches while the animal performs different behavioral patterns: crawling, swimming or shortening. Both the behaviors and neuronal recordings are monitored by a video camera system and can be evaluated simultaneously. The device is well suited to investigate questions of behavioral choice and neuronal decision-making mechanisms in these animals. It can also be modified to study the neural control of behavior in other aquatic animals, such as snails. PMID- 1405745 TI - A simple and rapid method for improving recording characteristics using multibarrelled micropipettes. AB - A method for the simple and rapid fabrication of multibarrelled micropipettes with improved signal-to-noise characteristics is described. The process of silicone coating the exterior of the multibarrel assembly was found to improve recording characteristics greatly and to reduce recording noise during the passage of ionophoretic current. This simple process of fabrication and silicone coating is completed within 15-20 min and is technically undemanding. PMID- 1405746 TI - NeuronC: a computational language for investigating functional architecture of neural circuits. AB - A computational language was developed to simulate neural circuits. A model of a neural circuit with up to 50,000 compartments is constructed from predefined parts of neurons, called "neural elements". A 2-dimensional (2-D) light stimulus and a photoreceptor model allow simulating a visual physiology experiment. Circuit function is computed by integrating difference equations according to standard methods. Large-scale structure in the neural circuit, such as whole neurons, their synaptic connections, and arrays of neurons, are constructed with procedural rules. The language was evaluated with a simulation of the receptive field of a single cone in cat retina, which required a model of cone-horizontal cell network on the order of 1000 neurons. The model was calibrated by adjusting biophysical parameters to match known physiological data. Eliminating specific synaptic connections from the circuit suggested the influence of individual neuron types on the receptive field of a single cone. An advantage of using neural elements in such a model is to simplify the description of a neuron's structure. An advantage of using procedural rules to define connections between neurons is to simplify the network definition. PMID- 1405747 TI - What is lymphology in 1991? PMID- 1405748 TI - Tissue tonometry: a useful tool for assessing filarial lymphedema. AB - A tissue tonometer was used to assess peripheral lymphedema in patients with filariasis in a Bancroftian endemic community. Matched populations of 34 patients with Grade II and 29 patients with Grade III unilateral lower limb edema and 26 healthy subjects were assessed for leg tissue compressibility and circumference. Tonometry was performed at three fixed points on the leg using three weight levels (70, 140, and 210 gms). The mean value of compressibility for each weight level and points measured in the edematous leg were significantly less compared with the contralateral non-edematous leg in the filarial patients and the legs of healthy subjects. Patients with Grade III lymphedema were more resistant to compression than Grade II patients throughout the leg but especially at the foot. The least mean square analyses of circumference and compressibility differential values of edematous compared with non-edematous legs revealed a positive correlation at the foot in Grade II and the proximal and distal parts of Grade III lymphedema; moreover, the slopes were significantly different from zero. These findings support progressive tissue changes of edema and fibrosis first in the foot and later in the more proximal portions of the leg which correspond to progressive volume expansion with protein-rich fluid. Tissue tonometry appears to be a sensitive measure for assessing progression of both edema and fibroplasia in patients with peripheral lymphedema associated with filariasis, and, therefore, may be a useful tool to measure the efficacy of drugs commonly used to treat this condition. PMID- 1405749 TI - Chyle leakage after blunt trauma. AB - Three patients developed chylous leakage after major blunt trauma. In one patient with non-remitting right-sided chylothorax, lymphangioscintigraphy as well as conventional oil contrast lymphography demonstrated disruption of the thoracic duct at the aortic hiatus which eventually required transpleural mediastinal ductal ligation proximal to the fistula. The other two patients had chylous retroperitoneum and/or chylous peritoneum which was self-limited although one patient (a three-year-old boy) died of multiorgan failure from associated pulmonary contusions and cervical spine injuries. Chylous leak after non penetrating trauma is usually attributed to hyperflexion-extension of the vertebral column with shearing of tethered lymphatics. Alternatively, sudden compression of lipemic and engorged mesenteric lymphatics, adjacent nodes and the lower thoracic duct aggravated by deformations associated with stretching and tearing motions may also directly disrupt chyle-containing lymphatics. PMID- 1405750 TI - The efferent cardiac lymphatic pathways in the macaque monkey. AB - In ten postmortem hearts of the Macaque monkey (M. mulatta), the coronary lymphatics were visualized using an India ink suspension in 2% gelatin. The left coronary lymphatic initially passed to the dorsal surface of the aortic arch. In five hearts, this lymphatic went directly to the cardiac lymph node, whereas in the others, it first ascended to the left superior tracheobronchial node and then interconnected with the cardiac lymph node. The right coronary lymphatic usually passed in front of the ascending aorta and common arterial (brachiocephalic) trunk and entered the cardiac lymph node. In two hearts, however, the right coronary lymphatic first ascended to an anterior transverse mediastinal node and from here lymphatics joined the cardiac lymph node. Those lymphatics that passed cephalad from the cardiac lymph node to the right anterior mediastinal nodes and the right paratracheal nodes ultimately emptied into the right venous angle. Those lymphatics that passed cephalad from the cardiac lymph node to the anterior transverse mediastinal nodes ultimately emptied into the left venous angle. In five other Macaque monkeys (M. mulatta and M. fascicularis) after marker injection (T1824 blue dye and micropulverized barium sulfate) into the living heart or pericardium, lymphatic drainage beyond the base of the heart could not be demonstrated. Whereas postmortem morphologic studies suggest that the monkey coronary lymphatic system is amenable to obstruction by removal of the cardiac lymph node and interruption of its adjacent lymphatic connections, effective methods for visualizing the mediastinal lymphatic collecting system in the living monkey must be developed before experimental cardiac lymphatic ablation can be accomplished in this species. PMID- 1405751 TI - Development of antiserum against veiled (dendritic) cells of canine afferent lymph: implications for transplantation biology. AB - A method is described for production of anti-veiled cell serum against veiled cells (VC) or dendritic cells obtained from canine skin lymph. By use of discontinuous Percoll gradient, VC from lymph were enriched to about 50% of the entire lymph cell population. After immunization of rabbits with the priming total dose of 10(7) VC (intramuscular, subcutaneous, intracutaneous) and with the same total booster injection (intravenous), the sera obtained were cytotoxic mainly for VC, with cytotoxin titer 1:16-1:32 and for agglutinin 1:256-1:512, respectively. Antisera used in vitro blocked the Ia and CD1 antigens of VC on smears and inhibited the accessory function of VC in cell response to phytohemagglutinin (PHA) and their stimulatory activity in mixed leukocyte reaction (MLR). In vivo, the local, intracutaneous administration of antisera led to transient depletion of VC from afferent lymph, and to reduction of mononuclear cells in the T-dependent areas in regional lymph nodes. PMID- 1405752 TI - Lymphatic vessels in the broad ligament of the uterus in swine. AB - The lymphatics of the broad ligament were depicted in 24 pigs by multiple interstitial injections of latex into the ovary and subserosa of the mesometrial margin of the uterine horn. Two morphologically different networks of lymphatics emanating from the uterus and ovary were established. Ovarian lymphatics leave the hilus, invariably enter the parovarian plexus, lie superficially under the perimetrium of the mesovarium, and run a parallel course closely intertwined with the blood vessels in this region. Some lymphatics are thus located close to the branches of the ovarian artery and the utero-ovarian vein. Whereas the ovarian and uterine lymphatics in the swine are not directly connected, the uterine lymphatics enter the mesovarium and lie in close proximity to both the ovarian lymphatics and nearby blood vessels. PMID- 1405753 TI - Differentiation and maturation of growth factor expanded human hematopoietic progenitors assessed by multidimensional flow cytometry. AB - Non-adherent cord blood and bone marrow mononuclear cells were analyzed by multiparameter flow cytometry before and at day 2, 4, 7, and 11 of culture in recombinant interleukin 3 (IL-3) and granulocyte colony-stimulating factor (G CSF, cord blood) or stem cell factor (SCF), IL3 and granulocyte-macrophage colony stimulating factor (GM-CSF, BM) to assess the differentiation and maturational pathway of myeloid cells. Before cell culture cord blood contained progenitor cells (CD34+) in various differentiation stages (CD38(-)----CD38bright), mature lymphocytes, monocytes, and neutrophils, but no immature neutrophils and immature monocytes. During cell culture, all CD34+ cells acquired the CD38 antigen between day 2 and 5 of cell culture, the CD34 antigen was lost between day 5 and 11 of cell culture. Differentiation of cells into the myeloid cell lineage was characterized by the acquisition of both CD33 and CD71. The latter is indicative for the active proliferation of these cells. Maturation of the cells into the neutrophilic pathway was indicated by the acquisition of first the CD15 antigen followed by CD11b and CD16 respectively. Whereas maturation of the cells into the monocytic pathway was indicated by the acquisition of first CD11b followed by CD14 and a dim expression of both CD15 and CD16. In normal bone marrow, cells of various maturational stages are already present before cell culture. During cell culture differentiation of cells into the myeloid lineage and maturation of the cells along the monocyte and neutrophilic lineage followed identical pathways as was observed before cell culture. Differentiation and maturational pathways of cord blood and adult bone marrow were identical. The results confirm the surface antigen-defined pathways of myeloid cell differentiation described previously for non-cultured normal bone marrow aspirates. The detailed assessment of cell maturation and differentiation of cultured cells by multidimensional flow cytometry permits the determination of the specific effects of various recombinant human growth factors on myeloid cells. PMID- 1405754 TI - The effects of IL-1 beta and IL-4 on the proliferation and endogenous secretion of growth factors by acute myeloblastic leukemic cells. AB - The effects of interleukin-1 beta (IL-1) and IL-4 were studied on the proliferation of acute myeloid leukemia (AML) cells. IL-1 stimulated tritiated thymidine (3H-TdR) uptake of AML cells in 8/12 cases, whereas IL-4 enhanced 3H TdR uptake in 5/12. Combination of both factors resulted in an additive effect in 6/12 cases which could be abrogated by the addition of anti-granulocyte macrophage colony stimulating factor (GM-CSF). To study whether IL-1, IL-4, or IL 1 plus IL-4 affects the AML progenitor cell directly or indirectly by the release of endogenous factors, supernatants of stimulated AML cells (n = 6) were analyzed for GM-CSF, IL-6, and tumor necrosis factor-alpha (TNF) production. IL-1 induced the endogenous secretion of GM-CSF, IL-6, and TNF in most cases. In contrast, no secretion of growth factors was induced by IL-4, whereas in 2 cases IL-4 suppressed the IL-1-induced secretion of GM-CSF, TNF, and IL-6. This was associated with a decline in the proliferative response to IL-1 measured in a clonogenic assay. In addition it was shown that exogenous supplied GM-CSF and TNF could raise the suppressive effects of IL-4 on the IL-1-supported proliferation. In summary these data indicate that the IL-4-supported proliferation is not caused by the endogenous secretion of GM-CSF, IL-6, and TNF. Furthermore the suppressive effect of IL-4 on the IL-1-induced proliferation in some cases may be caused by a reduced secretion of GM-CSF, TNF, and IL-6. PMID- 1405755 TI - Interleukin 2 production and interleukin 2 receptor expression by human immature leukemic T cells. AB - In order to determine the role of interleukin 2 (IL2) on the proliferation of leukemic cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) we studied the production of IL2, the function of IL2 receptors (IL2R) expressed on T-ALL cells and their IL-2-dependent in vitro proliferation. Leukemic cells from six out of 17 T-ALL/T-cell non-Hodgkin's lymphoma patients with a prothymocyte (stage I) or a mature thymocyte (stage III), but not with a common thymocyte (stage II) phenotype, could proliferate, in a dose-dependent manner, in response to recombinant IL2 (rIL2) and anti-Tac and TU27 moAbs as well as polyclonal anti IL2 purified immunoglobulin G could inhibit this IL2-induced cell proliferation. Both crude or/and Amicon-concentrated media conditioned by T-ALL cells from 10 out of 13 tested patients contained IL2 activity as assessed by colorimetric biological and immunoenzymatic assays; this biologic activity was due to a 14.5 kDa molecule adsorbed by anti-IL2 antibodies in an immunoaffinity assay. Although less than 10% of fresh leukemic cells expressed IL2R alpha (Tac) chain, a 24 h cell incubation in the absence of any mitogenic stimulation induced IL2R alpha chain expression in five out of 13 patients (11-83% Tac+ cells). Morever, Tac mRNA transcripts could be detected in fresh cells from all 10 patients tested. Staining of fresh leukemic cells with an IL-2R beta-chain-specific monoclonal antibody and flow cytometry analysis revealed that 4-13% of leukemic cells were positive. Binding experiments with 125I-rIL2 showed a small number of high affinity IL2R on fresh cells from three T-ALL patients (114-200 sites/cell, dissociation constant = 101-181 pm). Finally, antibodies against IL2R alpha, IL2R beta and IL2 could inhibit both IL2 driven and spontaneous cell proliferation of most patients' T-ALL cells, although in some cases an heterogenous pattern of inhibition was observed. Taken together, these findings strongly suggest that an IL2/IL2R-dependent mechanism could be involved in the proliferation of some T-ALL cells. PMID- 1405756 TI - Beneficial effects of post-transfusional hepatitis in acute myelogenous leukemia may be mediated by lipopolysaccharides, tumor necrosis factor alpha and interferon gamma. AB - Post-transfusional hepatitis is often a complication in patients with acute myelogenous leukemia (AML) in whom survival is paradoxically prolonged. The etiology is unknown. In previous studies, we showed that impaired hepatic endotoxin (lipopolysaccharide, LPS) clearance in patients with acute viral hepatitis A, B, or C versus controls results in endotoxemia and tumor necrosis factor alpha (TNF-alpha) release. TNF-alpha mediates anti-proliferative and differentiating effects in AML cell lines. Interferon-gamma (IFN-gamma) released in acute viral hepatitis, acts in synergy with TNF-alpha. HL60, KG1, and U937 AML cells treated 3, 6, and 9 days with physiologically attainable TNF-alpha (10 U/ml), IFN-gamma (100 U/ml) and LPS (10 ng/ml) levels, have significantly diminished viability and cell growth versus controls. Treatment of HL60 AML cells with LPS/TNF-alpha/IFN-gamma also resulted in significantly increased monocytic pathway differentiation not seen with KG1 or U937 AML cells. HL60 AML cells treated with TNF-alpha/IFN-gamma for 6 days released endogenous TNF-alpha (1.57 U/10(6) cells) upon LPS stimulation compared to less than 0.01 U/10(6) cells in non-LPS-stimulated TNF-alpha/IFN-gamma-treated cells or untreated cells (p less than 0.0001). Untreated HL60 AML cells co-cultured with HL60 cells pretreated for 6 days with TNF-alpha/IFN-gamma and then subjected to LPS stimulation had significantly diminished cell growth compared to controls (p less than 0.0001). This effect could be reversed with anti-TNF-alpha antibody, supporting the concept that endogenous TNF-alpha release by LPS/TNF-alpha/IFN-gamma treated HL60 AML cells may act by paracrine means to suppress growth of other AML cells. The beneficial effects of post-transfusional hepatitis in AML patients may be mediated via LPS/TNF-alpha/IFN-gamma-induced AML cell growth suppression and/or terminal differentiation in which AML cells participate by releasing TNF-alpha after being acted upon by LPS/TNF-alpha/IFN-gamma. Endogenously released TNF alpha might then act by autocrine/paracrine means to mediate further suppression and terminal differentiation. PMID- 1405757 TI - Inhibitory effects of AcSDKP on the mixed lymphocyte reaction (MLR). Part I. MLR with mouse spleen cells. AB - AcSDKP (inhibitor of entry into cycle of pluripotent hemopoietic stem cells) is able to decrease mixed lymphocyte reaction intensity when H-2 incompatible allogeneic spleen cells are used as stimulators. This is a first approach to determining whether AcSDKP has potential therapeutic value for clinical bone marrow transplantation. PMID- 1405758 TI - Inhibitory effects of AcSDKP on the mixed lymphocyte reaction (MLR). Part II. Human whole blood cells. AB - AcSDKP is a physiological negative regulator of hematopoietic stem cell proliferation. To investigate the applicability of AcSDKP in the prevention of graft-versus-host disease, this tetrapeptide was tested in mice and showed an inhibitory effect on the mixed lymphocyte reaction (MLR). In this paper we report MLR using human whole blood cells. The maximum inhibitory effect (50%) was obtained at 2.5 ng/ml AcSDKP. All experiments showed a constant dose response. Experiments are now being conducted to elucidate the mechanism of this inhibition. PMID- 1405759 TI - Dolastatin 10 and dolastatin 15: effects of two natural peptides on growth and differentiation of leukemia cells. AB - The effects of two natural peptides, dolastatin 10 and dolastatin 15, on growth and differentiation of hematopoietic cells were studied using freshly explanted leukemia cells and continuous leukemia cell lines. The proliferation of several myeloid cell lines and of growth-factor-stimulated peripheral blood cells from patients with acute myeloid leukemia (AML) was efficiently inhibited by the two agents at concentrations between 1 and 0.01 nM. Growth inhibition was dose dependent and reversible. Neither of the dolastatins exhibited significant cytotoxicity on dividing cells, nor did they interfere with the viability of resting cells. The 12-O-tetradecanoylphorbol 13-acetate or bryostatin I induced differentiation of AML cells was not affected by the dolastatins. Short-term exposure to the phorbol ester conferred reduced sensitivity of the cell line HL 60 to the antiproliferative effect of the drugs. Our data suggest that the dolastatins alone or in combination with other drugs could exert a role in the treatment of human myeloid leukemia. PMID- 1405760 TI - Resistance circumvention strategies tested in clinical leukaemia specimens using the MTT colorimetric assay. AB - We have used a 4-day MTT colorimetric assay to study drug sensitivity of leucocytes from leukaemia patients and from normal donors. Response to Adriamycin, vincristine, aclacinomycin A, 3'-deamino-3'-morpholino-13-deoxo-10 hydroxycarminomycin (MX2), and melphalan has been determined, together with the effects of the resistance modifiers verapamil, cyclosporin A, and ethacrynic acid. Sensitivity of chronic lymphoblastic leukemia (CLL) lymphocytes to vincristine was much greater than that of normal lymphocytes or of leucocytes from myeloid leukaemia patients. These cells were also more sensitive to melphalan. Verapamil and cyclosporin A at clinically achievable doses of 1 microgram/ml produced significant chemosensitisation in normal and leukaemic specimens, but the sensitisation ratio was greater than or equal to 2 only in a minority of specimens, except in the case of sensitisation to vincristine seen in the majority of CLL specimens. Sensitisation was generally greater in the more chemo-resistant specimens. The ratio of sensitivities of cells to Adriamycin compared with aclacinomycin A was greatest in the more Adriamycin-resistant specimens which supports the idea that cross-resistance between these agents may not be great. This was not, however, true for the ratio of Adriamycin/MX2 sensitivity. Use of the MTT assay may allow the identification of patients who would benefit from treatment with resistance modifiers or with 'low-resistance' anthracyclines. PMID- 1405761 TI - Phase II clinical trial of carboplatin in relapsed and refractory leukemia. AB - Carboplatin is a second-generation platinum complex drug which has demonstrated activity against a variety of neoplasms including acute leukemia, particularly when given by continuous intravenous (i.v.) infusion. Adults with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), either refractory or in first or second relapse, were given a continuous i.v. infusion of carboplatin at a dose of 315 mg/m2 daily for 5 days. A second course was given if the bone marrow at day 14 showed persistent leukemia. If the marrow was hypoplastic, treatment was delayed until marrow recovery was documented. Those with residual leukemia were given a second course. Those achieving complete remission (CR) were given an additional course as consolidation. Of the 46 eligible patients entered (36 AML and 10 ALL) eight achieved CR (17%) of which 6 were AML and 2 ALL. Of nine primary refractory patients, two achieved CR, one AML and one ALL. Excluding the inevaluable patients (protocol violations, patient refused further therapy, early deaths prior to day 14, the CR rate was eight of 28 (29%). All except two CRs required two courses of induction. The non hematologic toxicity was minimal except for renal and auditory toxicity. Renal toxicity greater than grade 2 was seen in 17 patients and was associated with concomitant use of nephrotoxic antibiotics. In two patients, renal failure was a major factor in the cause of death. Ototoxicity was observed in 11 patients, but was grade 3 in only three. There were 18 deaths during the study. Fourteen died of infection, two died of infection and hemorrhage, one died of hemorrhage while aplastic, and one died of other causes. This trial indicates that carboplatin is an active agent in acute leukemia and warrants further investigation. PMID- 1405762 TI - Prognostic relevance of serum beta 2-microglobulin in acute myeloid leukemia. AB - Serum levels of beta 2-microglobulin (S-B2m) were analysed at diagnosis in 69 cases of acute myeloid leukemias (AML) as a possible prognostic indicator. S-B2m was correlated to various clinical and laboratory features and with respect to response to chemotherapy and following clinical outcome. S-B2m was found to be increased (greater than 3 mg/l) in 40.6% of tested patients and, in particular, in the monocytic variants (M4, M5) of AML (4.2 versus 2.3 mg/l, p less than 0.01). S-B-B2m values paralleled white blood cell count, serum lysozyme levels and expression of monocytic membrane markers at presentation, but no correlation was found with age, renal function or immunological myeloid antigens. Increased levels of S-B2m were associated with a lower likelihood of obtaining a complete remission (25 versus 58.5%, p less than 0.01), while in the multivariate analysis S-B2m greater than 3 mg/l and white blood cell count greater than 20 x 10(9)/l were independent variables significantly influencing disease-free survival in responsive patients (five years DFS for S-B2m greater than or less than 3 mg/l: 28 versus 62%, p less than 0.05). In conclusion, the measurement of S-B2m at diagnosis may have prognostic relevance in AML. PMID- 1405763 TI - Summary of the European Stem Cell Club, Copenhagen, April 29-May 1, 1992. PMID- 1405764 TI - Anti-sense oligodeoxynucleotides--promises and pitfalls. AB - The high specificity of binding of oligodeoxynucleotides to their target mRNA has resulted in suggestions that these compounds may be useful as therapeutic agents against human cancer. While many successful anti-sense experiments have been reported in the literature, significant obstacles to widespread therapeutic use remain. These include nuclease sensitivity, non-sequence specificity, and uncertainties regarding optimum choice of mRNA target. Other significant problems include lack of information concerning cellular pharmacology and pharmacokinetics, and relatively little data concerning optimum dosing schedules. This review attempts to provide current information about these issues, which have such a strong impact on this exciting and rapidly growing field. PMID- 1405765 TI - Cell surface proteins of chicken hematopoietic progenitors, thrombocytes and eosinophils detected by novel monoclonal antibodies. AB - E26 is an acute avian leukemia virus that contains two nuclear oncogenes, v-myb and v-ets, and that is capable of transforming early cells of the erythroid and myeloid lineages. In another study, we have found that TPA (phorbol 12,13 dibutyrate) treatment of E26-transformants displaying an 'early erythroid' phenotype results in the production of cells with either myeloid or eosinophil characteristics. To analyze this induction in greater detail we have produced a panel of four monoclonal antibodies against E26-transformants before and after TPA-induced differentiation. Two antibodies, MEP21 and MEP26, reacted with proteins of 150 and 47-60 kDa, respectively, which are expressed on the surface of E26 progenitor cells but whose expression is extinguished following TPA induced differentiation. A third antibody, EOS47, recognizes a 100 kDa molecule that is expressed on the surface of TPA-induced peroxidase positive cells (an enzyme that in avian species is restricted to cells of the eosinophilic lineage). MEP21, MEP26, and EOS47 do not react with lymphoid, myeloid, or more mature erythroid lineage cell lines. The fourth antibody, MEP17, recognizes a heterodimer of 140 and 150 kDa chains which is expressed at high levels by E26 transformed progenitor cells and at lower levels by TPA-induced cells. Further biochemical characterization of the MEP17 antigen revealed a structure similar to that of the leukocyte adhesion molecule VLA-4; a member of the integrin family of adhesion proteins. All four antibodies react with subpopulations of cells in the bone marrow and spleens of 1-day-old chickens. Although the MEP21 and MEP26 antibodies do not appear to react with mature cells of most hematopoietic lineages they are expressed at high levels by mature thrombocytes. In addition, MEP17 is expressed at high levels by the majority of bursal B-cells, thrombocytes, and more weakly by thymocytes. The reagents described should be useful as markers for the study of development, migration, and differentiation of normal avian hematopoietic progenitor cells and eosinophilic precursors, and for the study of retrovirus-induced neoplasia. PMID- 1405766 TI - Ralph K. Ghormley, M.D.: Second Chairman of the Department of Orthopedics at Mayo. PMID- 1405767 TI - Musculoskeletal and soft tissue Aeromonas infection: an environmental disease. AB - During a 4-year period from November 1985 to November 1989, Aeromonas was isolated from wounds and soft tissues with clinical evidence of infection in 28 patients at our institution. Of the 28 patients, 23 (82%) had sustained an acute open or penetrating injury, more than half of which (13 of the 23) were water related trauma. One patient had Aeromonas osteomyelitis. Five patients had no history of trauma, and three of these five had an underlying chronic disease. Treatment included debridement and antimicrobial agents. Susceptibility testing on 25 isolates from 23 patients showed uniform resistance to ampicillin and considerable resistance to cefazolin sodium (68%), but all isolates were sensitive to gentamicin sulfate, cefuroxime sodium, and the third-generation cephalosporins. PMID- 1405768 TI - Familial amyloidosis: a study of 52 North American-born patients examined during a 30-year period. AB - Between 1961 and 1990, 52 patients with biopsy-proven familial amyloidosis born in North America were examined at the Mayo Clinic. At the time of diagnosis of familial amyloidosis, 83% of these patients had peripheral neuropathy, 33% had autonomic neuropathy, and 27% had cardiomyopathy. Renal disease was noted in fewer than 10%, and liver involvement was rare. The median age at diagnosis was 64 years. The sensitivity of various diagnostic biopsies was similar to that for primary amyloidosis: deposits of amyloid were found in 77 and 78% of the subcutaneous fat aspirates or rectal biopsy specimens, respectively, and in 41% of specimens of bone marrow. The median duration of survival of 5.8 years for patients with inherited amyloidosis was superior to that for patients with primary amyloidosis. When patients were stratified by organ involvement, the survival of patients with familial amyloidosis remained superior. The presence of cardiomyopathy and an interactive variable of age and the presence of autonomic neuropathy were powerful predictors of survival. Of the 52 patients, 22 died, 12 (55%) of cardiac failure or cardiac arrhythmia. Nine patients (41%) died of inanition in conjunction with progressive peripheral or autonomic neuropathy. Transthyretin was identified by immunohistochemical studies in 31 of the 34 tissue specimens tested. A transthyretin mutation was identified in 24 of the 31. A transthyretin mutation was found in five additional patients for whom tissue was unavailable for immunostaining. PMID- 1405769 TI - Laparoscopic cholecystectomy: operative technique. AB - Laparoscopic cholecystectomy has become the routine procedure for most patients with symptomatic cholelithiasis. At our institution, a two-surgeon, four-cannula technique is used. In almost all patients, a pneumoperitoneum can be established with use of a closed technique. Adherence to standard operative principles and careful attention to details in the laparoscopic technique will routinely result in the safe completion of laparoscopic cholecystectomy. Cautery provides excellent hemostasis during dissection of the gallbladder from its attachments. Cholangiography through the gallbladder or the cystic duct is easily performed in selected patients. Minimal perioperative care is necessary for patients who undergo laparoscopic cholecystectomy, and the hospitalization time is usually less than 24 hours. PMID- 1405770 TI - Laparoscopic cholecystectomy: early Mayo Clinic experience. AB - Prospective data and follow-up information were collected on the initial 200 patients who underwent laparoscopic cholecystectomy at the Mayo Clinic. The operation was completed laparoscopically in all but five patients, who required conversion to laparotomy because of dense scarring or stones in the common bile duct. The median surgical time was 85 minutes. The major postoperative complications were retained stones in the common bile duct (in seven patients), intraperitoneal hemorrhage that necessitated transfusion (in two patients), and intra-abdominal abscess and pulmonary infection (in one patient each). The median hospital stay was 1 day (range, 0 to 8 days), and the median times to full activity and normal employment were 8 days and 12 days, respectively. Laparoscopic cholecystectomy is associated with a low frequency of complications in most patients with symptomatic gallstones and allows a rapid return to normal activity. Currently, laparoscopic cholecystectomy is the treatment of choice for most patients with symptomatic cholelithiasis. PMID- 1405771 TI - A clinical update on chronic lymphocytic leukemia. II. Critical analysis of current chemotherapeutic modalities. AB - Not all patients with B-cell chronic lymphocytic leukemia require therapy. Patients with stable early stage disease do not need treatment, whereas those with progressive early stage disease or advanced stage disease do. The standard initial therapeutic regimen is orally administered chlorambucil and prednisone. The overall response rate to initial chemotherapy is approximately 80%; the median duration of response is 2 years. Conventional chemotherapy, however, does not provide long-term remission for patients in whom the disease becomes refractory to chlorambucil. For such patients, alternative treatment approaches including the use of purine nucleoside analogues or bone marrow transplantation may be considered. Fludarabine, 2-chlorodeoxyadenosine, and pentostatin are three analogues of the naturally occurring deoxypurine nucleoside, deoxyadenosine, and all have shown activity in chronic lymphocytic leukemia. Overall response rates of 57 to 79% have been reported with use of fludarabine. A dose-related toxic effect is myelosuppression. Experience with bone marrow transplantation is limited. The number of eligible patients with histocompatible sibling donors is low. The future role of allogeneic bone marrow transplantation in patients with B cell chronic lymphocytic leukemia will depend on the ability to identify poor risk groups and the long-term therapeutic efficacy of the purine nucleoside analogues or other new agents. PMID- 1405772 TI - Video-assisted thoracic surgical procedure: management of a solitary pulmonary nodule. AB - Solitary pulmonary nodules continue to challenge all diagnostic skills. Herein we describe video-assisted thoracic surgical intervention, a new, minimally invasive technique that aids physicians in obtaining a definitive histologic diagnosis in a select group of patients with an indeterminate solitary pulmonary nodule. PMID- 1405773 TI - Nicotinic acid-induced toxicity associated with cytopenia and decreased levels of thyroxine-binding globulin. AB - We report the occurrence of cytopenia and hypothyroxinemia attributed to decreased levels of thyroxine-binding globulin in patients receiving nicotinic acid. We describe two patients in whom hypothyroxinemia developed while they were taking nicotinic acid; these patients also had decreased levels of thyroxine binding globulin. Results of all thyroid function tests returned to normal when use of the nicotinic acid was discontinued. In one patient, leukopenia and thrombocytopenia developed during nicotinic acid therapy alone. These conditions were reversed after the drug regimen was discontinued. In another patient, leukopenia and thrombocytopenia developed during combination nicotinic acid and lovastatin therapy. When administration of both drugs was discontinued, the hematologic abnormalities, which could have been due to either nicotinic acid or lovastatin, diminished. We suggest that cytopenia may develop in patients receiving nicotinic acid; thus, thyroid function tests should be interpreted in light of a possible decreased level of thyroxine-binding globulin. PMID- 1405774 TI - Thermoregulation and fever in normal persons and in those with spinal cord injuries. AB - Thermoregulation and fever are primarily mediated through the hypothalamus and its effector mechanisms. In persons with complete spinal cord injuries above T-6, thermoregulation is substantially impaired because of the interruption of neuronal pathways to and from the hypothalamus. These same pathways are important in the production of fever in response to infections, and injury to these pathways in patients with high-level spinal cord injuries should diminish their ability to mount a febrile response. In clinical practice, however, measurements of body temperature are used to make decisions in patients with spinal cord injuries in a manner similar to that in patients without spinal cord injuries. In this article, we review the literature on thermoregulation and fever in normal persons and in those with complete spinal cord injuries and propose possible mechanisms for fever in persons with high-level spinal cord injuries. PMID- 1405775 TI - Medical mythology: Aphrodite (Venus). PMID- 1405776 TI - The development of cardiac transplantation. AB - The history of cardiac transplantation provides an excellent prototype for the development of a therapeutic technique. The first observations on cardiac transplantation were made in animal models in the early 20th century. Surgical problems were solved through a series of technologic advances, and problems associated with immune-mediated rejection were discovered and successfully addressed. By the late 1960s, cardiac transplantation in humans had become feasible. Since the first successful transplantation of a heart in a human in 1967, the management of rejection and infection has steadily progressed, and the long-term outcome after cardiac transplantation has improved dramatically. The success of cardiac transplantation has led to an expansion of the potential recipient pool to include children and adults in the eighth decade of life. Unfortunately, the growth of cardiac transplantation has resulted in an inadequate supply of suitable donor hearts. The limited supply of donor hearts has provided the impetus for further research in xenotopic cardiac transplantation and for the development of implantable circulatory assist devices. PMID- 1405777 TI - Prognostic features in patients with congestive heart failure and selection criteria for cardiac transplantation. AB - Cardiac transplantation can be a highly successful therapeutic option for patients with end-stage congestive heart failure. Successful results, however, depend on the appropriate selection of patients for the procedure. Patients whose survival or quality of life would be compromised without cardiac transplantation and who are likely to benefit from this intensive type of treatment are potential candidates. Each patient should undergo a thorough assessment to identify any medical or psychologic contraindications to cardiac transplantation. In this review, we discuss the important predictors of survival in patients with congestive heart failure: the cause of heart failure, the patient's symptomatic and functional status, the hemodynamic and pathologic findings, the evaluation of neurohumoral activity, and the presence of cardiac arrhythmias. Once a patient with congestive heart failure has been identified as having a limited life expectancy and severely impaired quality of life, cardiac transplantation should be considered. PMID- 1405778 TI - Extraintestinal Aeromonas infections--looking for Mr. Sandbar. PMID- 1405779 TI - Thoracic manifestations after esophageal variceal sclerotherapy. PMID- 1405780 TI - Prophylactic recommendations for bite wounds. PMID- 1405781 TI - Immunohistochemical study of extracellular material in the aged human synovial membrane. AB - Types III, IV, VI collagen and laminin distribution in synovial tissue of seven autopsy knee joints from old human donors (69-94 years of age) were investigated with immunocytochemical and immunohistochemical methods. The synovial intima is separated from the subintimal tissue by an intermediate fibrillar zone rich in staining for type III collagen. In the intima basement membrane-like material associated with synovial lining cells stains for type IV collagen and laminin. Fine fibrils surrounding the lining cells stain for type VI collagen. In two of the cases type VI collagen occurs mainly as long-spacing collagen, the distinct aggregated form of type VI collagen. This staining pattern was qualitatively the same in all different regions and cases investigated. However, considerable quantitative differences were seen. PMID- 1405782 TI - The effect of aging on protein synthesis in the yeast Saccharomyces cerevisiae. AB - The protein synthetic rate in the yeast S. cerevisiae, measured by the incorporation of radioactive amino acids per unit amount of proteins, decreased linearly with age reaching 50% of the rate of 2nd generation cells (young cells) in 20th generation cells (old cells), whereas the RNA content of the old cells was increased three times. Using a cell-free system for poly(U)-directed poly phenylalanine synthesis, the activity of run-off ribosomes from old cells was shown to be about 40% less than the activity of ribosomes from young cells and the polysome level in old cells was much decreased compared to that in young cells. However, as protein content was increased twice in 20 generations, the cell is considered to maintain a constant level of protein synthesis during the process of aging compensating the decrease in the activity of ribosomes. Thus, it is likely that the decrease in the synthesis of certain proteins whose requirement was raised by the increase in cell volume, which is twice the increase in protein content, causes prolongation of the unbudded phase in old cells. PMID- 1405784 TI - Formation of cerebrovascular anomalies in the ageing rat is delayed by chronic nimodipine application. AB - At the ultrastructural level two main categories of microvascular anomalies can be distinguished in the aged rat brain. These categories comprise [1] membranous inclusions within the basement membrane and [2] microvascular deposits, which include microvascular fibrosis and thickening of the basement membrane (BMT). In this study we examined the percentage of microvessels displaying ageing-related malformations in the frontoparietal motor cortex of rats aged 16, 24, 30 and 32 months. The percentage microvessels with membranous inclusions and microvascular deposits both gradually increased until the age of 30 months, after which no further increase was observed. The percentage fibrotic microvessels, however, increased until the age of 30 months, but was decreased at 32 months. This decrease of fibrotic microvessels at 32 months coincided with a proportional increase of cerebral microvessels provided with a thickened basement membrane. Combined with qualitative observations these data suggest that in a very late stage of the ageing process collagen fibrils in microvascular fibrotic plaques are depolymerized and degradated. By this mechanism it appears that microvascular fibrosis is transformed into basement membrane thickening. Long-term application of the calcium entry blocker nimodipine did not influence the amount of microvessels with membranous inclusions within the basement membrane, but in contrast resulted in a prominent reduction of ageing-related microvascular deposits when administered from 24 to 30 months. The effect of a prolonged nimodipine treatment from 24 to 32 months on the amount of microvascular deposits was still significant, however, much less conspicuous. We now conclude that chronic administration of nimodipine delays the formation of microvascular deposits up to the age of 30 months. Furthermore, the beneficial effect of nimodipine treatment from 24 to 30 months on microvascular integrity is not accompanied by a reduced systolic blood pressure. PMID- 1405783 TI - In vivo microscopic studies of age-related changes in the structure and the reactivity of cerebral microvessels. AB - To determine if hemodynamic changes in cerebral microvessels could contribute to the age-related changes in the blood-brain barrier (BBB) function, the cerebral microvessels of male Fischer 344 rats at different ages were studied using intravital fluorescence microscopy. Aging in rats was associated with significant arteriovenous shunting in the cerebral microvessels without alterations in blood flow characteristics or changes in vascular permeability to FITC dextran (150 kDa). The basal diameter of terminal arterioles examined in 24- to 27-month-old (aged) rats (28.6 +/- 2.8 microns) was not different from that in 12- to 15-month old (intermediate age) rats (32.5 +/- 2.5 microns) or in 3- to 6-month-old (young) rats (28.6 +/- 3.0 microns). At 3 s following addition of 5% BaCl2 there was 23.3 +/- 3.47% constriction of arterioles in young rats and 14.8 +/- 5.16% constriction in intermediate age rats, but only a 3.43 +/- 5.69% change in aged rats (P less than 0.03). This initial brief constriction phase was followed by a dilatory response which was similar in all age groups. One minute following suffusion with artificial cerebrospinal fluid, the arteriolar diameter essentially returned to baseline in all rats examined. It is concluded that aging in rats is associated with alterations in cerebral microvascular reactivity in vivo along with arteriovenous shunting. These changes may contribute to age related alterations in the BBB function. PMID- 1405785 TI - Age-related alterations in antioxidant capacity and lipid peroxidation in brain, liver, and lung homogenates of normal and vitamin E-deficient rats. AB - Age-related alterations in both antioxidant capacity and lipid peroxidation in the cerebrum, lung and liver homogenates of normal and vitamin E-deficient rats were investigated. The antioxidant capacity, which includes superoxide dismutase, catalase and glutathione peroxidase activities and vitamin E (alpha-tocopherol) concentration, was relatively stable throughout the lifespan. It was observed, however, that catalase and glutathione peroxidase activities in livers of old rats decreased and that vitamin E concentration in lung and liver increased with age. In vitamin E-deficient animals, catalase activity in liver increased and glutathione peroxidase activity in liver and lung decreased. Lipid peroxidation was monitored by use of three different indices, i.e. the thiobarbituric acid (TBA) value, oxygen absorption and conjugated-diene formation. In the absence of any initiator, neither oxygen absorption into tissue homogenates nor conjugated diene formation in lipid extracts from the homogenates occurred. The TBA value of each cerebrum homogenate incubated under air or an oxygen atmosphere was larger than that of the corresponding unincubated cerebrum homogenate. From comparison between the TBA value and oxygen absorption, this increase in the TBA value was suggested to be due to some reactions other than lipid peroxidation. Although tissue homogenates examined contained TBA-reacting materials, no lipid peroxidation seems to arise during incubation of them. No age-related alterations in the TBA value and oxygen absorption in rat tissue homogenates were observed. Vitamin E deficiency had no effect on the TBA values of cerebrum and lung homogenates, while it seemed to increase the TBA values of liver homogenates. Vitamin E deficiency had no effect on oxygen absorption in these tissue homogenates. The induction period of initiator-induced conjugated-diene formation in lipid extracts from liver and lung homogenates from normal and vitamin E deficient rats tended to be extended with age. Vitamin E deficiency decreased the induction period of initiator-induced conjugated-diene formation. As a result, the length of the induction period was found to be proportional to vitamin E concentration in lipid extracts. The overall antioxidant capacity of rat tissues appears to be maintained without large variation during ageing. Decreases in the capacity of some antioxidant factors may be compensated by increases in the capacity of other factors. PMID- 1405786 TI - Chromatography and spectrofluorometry of brain fluorophores in neuronal ceroid lipofuscinosis (NCL). AB - The aim of the present work was to develop a chromatographic system for the separation of individual fluorophores extracted from neuronal ceroid lipofuscinosis (NCL) brain and isolated storage bodies. Extracts from gray matter were best resolved on silica-gel HPTLC plates using a mixture of chloroform/methanol/water (55:45:10 by vol.). Two other chromatographic systems were tested which gave poorer separation. Corrected fluorescence spectra were obtained on the original extract and fluorescence intensity, especially at longer wavelengths was increased in both samples. Yellow and blue fluorophores were detected on HPTLC plates using a primary violet and secondary yellow filter with cut-off levels of 400 and 520 nm, respectively. Plates were photographed at 20 min, 2 h and 1 week after chromatography. With this filter system, up to 12 yellow bands of differing intensity were observed at 20 min but with time, some of these changed to blue as a result of autoxidation. NCL tissues emit yellow fluorescence when viewed under light microscopy, however extracted material did not demonstrate a distinct peak in this region of the spectrum which should be around 575 nm. HPTLC confirmed this observation and time studies revealed that autoxidation changes occur and must be carefully controlled to reduce artifacts. The discrepancy between extracted and non-extracted observations may be the result of superposition of multiple fluorophores with differing maxima and/or a self-absorption phenomenon. The combination of chromatographic separation and spectral analysis as described in this study, may be a valuable technique to further clarify the characteristics of compound fluorescent lipopigments. It is suggested that NCL fluorophores of human brain differ in their properties from other models. PMID- 1405787 TI - The effect of age, sex and breeding on graft versus host reactivity of spleen cells from C57BL mice. AB - Spleen cell graft versus host (GvH) reactivity was determined in male and female, either virgin or breeder, C57BL mice from 3 to 24 months of age. The GvH reaction was assessed by a local popliteal lymph node assay and by a splenomegaly test for a systemic reaction. Although the GvH reactivity declines progressively with age in both sexes the virgin female response was greater than that of males throughout the period of 6-18 months of age. Two-year-old mice of both sexes were practically unable to mount a GvH reaction. No differences were evident in aging female reactivity after one or two syngeneic pregnancies. On the other hand, 3 or more consecutive pregnancies resulted in enhanced GvH reactivity of 12-24-month old females, which responded comparably to young virgin mice. This long-lasting immunopotentiating effect of multiparity was similar after 3-4 and 8-9 pregnancies. The possible role of developing foetuses on the maintenance of high GvH reactivity in breeder females is suggested. PMID- 1405788 TI - Effect of age-related lipid peroxidation on membrane fluidity and phospholipase A2: modulation by dietary restriction. AB - Age-related changes in membrane property are generally accepted phenomena. In this report, using the anti-lipoperoxidative measure of dietary restriction on membranes, the age-related effects of lipid peroxidation on membrane fluidity are explored in conjunction with the membrane-associated phospholipase A2. The fluidity of mitochondrial and microsomal membranes from ad libitum fed rats shows a progressive decline with age as indicated by a substantial decrease in two parameters, l/polarization and l/anisotropy. In contrast, the membrane fluidity of dietary restricted rats shows slight changes between 6 and 24 months of age. Evidence is presented to support the possibility that age-related peroxidation of membrane lipids may play a significant role in bringing about fluidity changes in aged membranes. The findings on the increased phospholipase A2 with age is also consistent with this conclusion. PMID- 1405789 TI - Ontogenic characteristics of cavian aldolase. AB - In order to extend the available information on the ontogenic significance of the interactions between aldolase and cellular structure, the nature and extent of these associations have been studied in the tissues of the guinea pig during development, along with analyses of the isozyme status in the bound and soluble compartments. In all tissues investigated, a significant degree of binding was evident, along with a considerable variation in the degree of association of aldolase with structure during development. Binding was particularly extensive in the early foetal stages and, in general, binding preference was directed towards A-type activity over the B- and C-type of enzyme. The significance of these ontogenic phenomena have been discussed in relation to the variations in phenotype of individual tissues during maturation and the metabolic correlations of this biphasic micro-organization. PMID- 1405790 TI - Developmental profiles of antioxidant enzymes and trace metals in chick embryo. AB - It has been previously well documented that partial pressure of oxygen (PO2) and weight-specific rate of O2 consumption in chick embryo (Gallus gallus domesticus) transiently increase midway through the 21-day in ovo incubation period. The present study found that these oxidative changes were paralleled by the concentrations of glutathione (GSH) and Zn in liver and by the specific activity of superoxide dismutase (SOD) in brain. Levels of antioxidant enzymes and their trace metal cofactors were markedly higher in liver than in brain. Hepatic catalase activity changed in parallel with the concentration of its cofactor, Fe. However, the relative abundance of metal cofactors did not appear to be the determining influence on other antioxidant enzyme activities. Rates of extra mitochondrial hydrogen peroxide release were also much greater in liver than in brain. Taken together, the results of this initial study of embryonic chick antioxidant systems suggest that certain antioxidants may be regulated by PO2 and rate of oxidative metabolism during fetal development. PMID- 1405791 TI - Aging as a multi-step process characterized by a lowering of entropy production leading the cell to a sequence of defined stages. II. Testing some predictions on aging human fibroblasts in culture. AB - The concepts of irreversible thermodynamics have been used in order to develop a theory of aging considered as a multi-step process leading the cell through a sequence of defined stages characterized by a lower level of entropy production and finally to a critical level of errors involving cell death (Toussaint et al., 1991). One of the predictions of this model is that external stresses which can be considered as fluctuations would accelerate the evolution of the cell from one state to the other according to the intensity of the stress. Seven morphotypes have been observed in the serially cultivated human fibroblasts, cells passing progressively from one morphotype to the other. In this paper, we experimentally tested the effect of two different molecules, tert-butylhydroperoxide and ethanol, in order to determine their influence on the shift from one morphotype to the other. When applied for a single period of time on cultivated cells, both molecules effectively showed a modification in the pattern of the different morphotypes which was dependent on the stress intensity: a decreased proportion of the early morphotypes and an increased proportion of the late and post-mitotic morphotypes were observed within three days after the stresses. Similar results were obtained when successive stresses were performed at every subculture. The results also indicated that all stages are not equally stable with morphotypes III and IV being the most stable. The positive effect on the increased shift of these cells from one morphotype to the other by two different stresses firms one of the prediction of the thermodynamic model which states that cellular aging can be considered as a multi-step process which can be speeded up by various external modifications. PMID- 1405792 TI - The proliferation theory of rejuvenation. AB - A theory concerning the molecular basis of rejuvenation is presented that postulates a central role for cell proliferation. This theory assumes that aging is due to the accumulation of multiple forms of molecular damage and that rejuvenation is due to repair. The advantages of proliferation as a means of repair are described and it is proposed that cell proliferation is required for full rejuvenation. This proliferation theory offers several advantages: a different perspective on the question of which organisms age; an explanation of aging-related phenomena that are not well handled by traditional aging theories; a novel approach to altering the aging rate; and testable implications for the design of new experimental systems and therapeutic interventions. PMID- 1405793 TI - Fragile sites, Alzheimer's disease, and aging. AB - The fragile site expression under conditions of folate deprivation was compared in the chromosomes from 5 Alzheimer's disease (AD) female patients, 5 healthy elderly females and 5 healthy young females. Although different fragile sites were observed in the three groups, nevertheless, more similarities were found between the AD patients and elderly normal donors. The only fragile site common to all groups was 3p14. This site was the most frequent in the young donors group. In both AD and elderly control groups we observed a higher frequency of fragility in 6p21, but not in the young controls. Other interesting fragility points observed in these two groups were: 6q21 and 14q24 (in the AD patients) and 9q13, 14q24 and 17q21 (in the healthy aged). 6p21 and 17q21 have been proposed as 'new' fragile sites. We confirm the existence of these fragile sites and comment that in these bands the genes MTBT2 and MTBT1, which are microtubule (beta) associated protein tau-like and tau 1, respectively, are mapped. The tau protein is a component of paired helical filaments which accumulate in degenerating neurons in the brain of patients with AD and with less intensity of normal elderly individuals. PMID- 1405794 TI - The Medicare cost of renal dialysis. Evidence from a statistical cost function. AB - Medicare's End Stage Renal Dialysis Program currently costs more than $6 billion per year, which covers renal dialysis, kidney transplants and other life-saving medical care for 190,000 patients of all ages suffering from chronic renal failures. Medicare reimburses dialysis units for dialysis treatments using a formula based on accounting costs reported by a small sample of facilities. However, accounting methods may obscure the true economic costs of providing the different type of dialysis treatments such as hemodialysis, continuous ambulatory peritoneal dialysis, and continuous cycling peritoneal dialysis. In this study, a multiproduct, statistical cost function approach to obtain cost estimates was used. Results obtained in this study show that the average cost and marginal cost of hemodialysis treatments are generally in line with current reimbursement rates, whereas the average and marginal costs of continuous ambulatory peritoneal dialysis treatments may be below this rate. For in-center hemodialysis, which is the mainstay of all dialysis units, the authors found evidence of decreasing economies of scale at the mean facility size, but found constant returns to scale for other modalities. Some evidence of economies of scale from chain ownership of dialysis centers was discovered. Finally, the analysis indicates that the Medicare reimbursement formula may be outdated, and further research that could lead to the design of more "rational" payment rules is suggested. PMID- 1405795 TI - Clinical versus administrative data bases for CABG surgery. Does it matter? AB - This study compared the ability of a clinical and administrative data base in New York State to predict in-hospital mortality and to assess hospital performance for coronary artery bypass graft surgery. The results indicated that the clinical data base, the Cardiac Surgery Reporting System, is substantially better at predicting case-specific mortality than the administrative data base, the Statewide Planning and Research Cooperative System. Also, correlations between hospital mortality rates that are risk-adjusted using the two systems were only moderately high (0.75 to 0.80). The addition of new risk factors from the Statewide Planning and Research Cooperative System improved the predictive power of both systems but did not diminish the difference in effectiveness of the two systems. The three unique clinical risk factors in the Cardiac Surgery Reporting System (ejection fraction, reoperation, and more than 90% narrowing of the left main trunk) seemed to account for much of the difference in effectiveness of the two systems. PMID- 1405796 TI - The inequality of medical expenditures for several years in a healthy, nonelderly population. AB - Previous studies have shown that the distribution of annual medical expenditures for a population is very unequal and remains so for periods of more than 1 year. The authors use a better measure of inequality, the Gini coefficient, to test its persistence for longer periods. This measure is applied to data collected from the Rand Health Insurance Experiment. The experiment enrolled a nonelderly population typical of those covered by employer health plans for periods up to 5 years. The distributions of annual expenditures for this population are highly unequal, in line with previous studies. Inequality declines substantially when longer periods are considered. PMID- 1405797 TI - Comparative measurement sensitivity of short and longer health status instruments. AB - Short measures of health status are used increasingly in health services research, yet their sensitivities to clinical change have not been compared with longer, established instruments. In this study, 5 health status measures were administered preoperatively and 3 months postoperatively to 54 patients undergoing total hip arthroplasty. These instruments included the Sickness Impact Profile (SIP)--an established, long measure--and 4 short forms: the SF-36, Functional Status Questionnaire, shortened Arthritis Impact Measurement Scales, and Modified Health Assessment Questionnaire. Scores for physical, psychological, and global dimensions were constructed by aggregating subscales. Sensitivity to change, or responsiveness, was expressed with the standardized response mean (SRM), calculated as the mean change in score divided by the standard deviation of the change in score. The sampling distribution of the SRM was estimated with a jackknife procedure. Preoperative scores were moderately to highly correlated across instruments. The physical and global dimension SRMs of the brief health status measures ranged from 0.85 to 1.27 and were as large as or larger than the corresponding SIP SRMs. The SIP had the highest SRM on the psychological dimension. None of the instruments was significantly more sensitive than the others at the critical value (P = 0.005) adjusted for multiple comparisons. The brief health status measures were equally or more responsive than the SIP after total hip arthroplasty in the physical and global dimensions. Much larger samples are required to demonstrate statistically significant differences in SRMs among instruments. PMID- 1405798 TI - Prescribing problems and pharmacist interventions in community practice. AB - Interventions performed by 89 community pharmacists in 5 states to correct the prescribing problems they identified on new prescription orders were documented by trained observers. Pharmacists intervened to resolve a prescribing-related problem in 623 (1.9%) of 33,011 new prescription orders that were screened and dispensed during the study period. A panel of three expert evaluators concluded that 28.3% of the prescribing problems identified during the study could have caused patient harm if the pharmacist had not intervened to correct the problem. The rate at which pharmacists identified prescribing problems was negatively related to the number of prescriptions they dispensed per hour, suggesting that in pursuing distributive efficiency, some pharmacists may be exceeding their safe dispensing threshold. The authors recommend that the interprofessional system of oversight and verification (i.e., "checks and balances") in the delivery of pharmaceutical care in the community setting should be maintained and strengthened. PMID- 1405799 TI - Health status and use of services among families with and without health insurance. PMID- 1405800 TI - Asking about the usual source of care. An appraisal of health care survey alternatives. PMID- 1405802 TI - Discrepancies between women's personal interview data and medical record documentation of illicit drug use, sexually transmitted diseases, and HIV infection. PMID- 1405801 TI - Comparison of Quality of Well-Being scale and Functional Status Index in patients with atrial fibrillation. PMID- 1405803 TI - [Monocytic dysfunction by opioid peptides in patients with major depression]. AB - BACKGROUND: Patients with depression present immunodepression and it has been proposed that, in these patients, endogenous opioid peptides may be mediators between the dysfunction of the central nervous system and immune alterations. METHODS: The function and the surface markers of monocytes were studied in 15 patients with major unipolar depression and in 24 healthy controls by biological trials of phagocytosis of Candida albicans and latex particles and immunofluorescence with monoclonal antibodies. RESULTS: Most of the patients studied (86%) presented monocytic dysfunction characterized by diminished phagocytic activity and a decrease in the expression of intermediate filaments of vimentin of the cytoskeleton and membrane molecules (CR1, receptor for the Fc fraction of the IgG and HLA DR antigens). Incubation of the patients monocytes with naloxone led to the disappearance of monocytic alterations in most of the patients. CONCLUSIONS: Patients with major unipolar depression present a high opioid tone which has consequences in the function of the immune system. PMID- 1405805 TI - [The impact of infection by the human immunodeficiency virus in the organization of health care services: new alternatives in health care]. PMID- 1405804 TI - [Evaluation of the demand for tests for the detection of anti-human immunodeficiency virus antibodies in Catalonia]. AB - BACKGROUND: Most programs for the control of the acquired immunodeficiency syndrome (AIDS) contemplate the registry of cases as the principal source of information. Despite the fact that these data have permitted important epidemiologic and clinical aspects of the disease to become known epidemiologic surveillance systems should be developed based on the detection of infection by the human immunodeficiency virus (HIV). METHODS: The prevalence and the epidemiologic profile of patients who underwent an anti-HIV test were studied in 17 hospitals in Catalonia in 1989. In addition, a questionnaire concerning demographic and epidemiologic variables was completed by all the patients in whom an ELISA test had been carried out during 4 periods of 15 days. RESULTS: During this period 33,012 serologic tests were performed in 17 centers with a global prevalence of positive results of 20.7% (IC 95% = 20.2%-21.1%). The greatest number of positive serologies corresponded to the collective of intravenous drug users (IVDU), consisting of 68% of all the positive tests with a prevalence of infection of 76.4%. Prevalence was considered as constant throughout the year despite the differences between the prevalence observed in some periods. CONCLUSIONS: The fact that the collective of intravenous drug users is most prevalent among the patient with positive results in the serologic detection of the human immunodeficiency virus (HIV) confirms that this is the principal group of transmission in Catalonia. This type of study may provide information on the rate of infection by HIV complementing other surveillance methods of the epidemic. However, the basic function of these tests stems from the study of the demand and use of detection tests. PMID- 1405806 TI - [Psittacosis, only in birds?]. PMID- 1405807 TI - [Familial outbreak of pneumonia by psittacosis]. AB - A familial outbreak (4 cases) of pneumonia by psittacosis in Vall de Uxo (Castellon) during the month of April in 1990 is described. In addition to the epidemiologic, clinical and serologic (complement fixation) studies carried out a survey and serology of 11 healthy controls (neighbors, and employees from a bird shop) were performed. The serum of a parrot recently acquired by the patients (positive at 1/8) was analyzed. The habit of petting the animal was significantly associated with the disease. The patient's response to treatment was good. The titers of antibodies versus Chlamydia psittaci were higher than those of the controls examined and the established threshold for positivity (1/36). In addition to clinical intervention the roles of epidemiology and the participation of veterinary services are fundamental to control this disease the exact prevalence of which is unknown. PMID- 1405808 TI - [Polymerase chain reaction. Should it be used in clinical microbiologic laboratories?]. PMID- 1405809 TI - [Human genetics: diagnostic and preventive impact of new genetics in medicine]. PMID- 1405810 TI - [Hyperthyroidism, another cause of hyperferritinemia]. PMID- 1405811 TI - [Tetany in a patient with the acquired immunodeficiency syndrome treated with foscarnet]. PMID- 1405812 TI - [Bacteremia from Campylobacter jejuni in a cirrhotic patient with ascites]. PMID- 1405813 TI - [Pustular eruption induced by norfloxacin]. PMID- 1405814 TI - [Statural growth during treatment of infantile hypercholesterolemia]. PMID- 1405816 TI - [Biased selection and confusion factors]. PMID- 1405815 TI - [Esophageal tuberculosis. Not so infrequent]. PMID- 1405817 TI - Travel medicine. PMID- 1405818 TI - Travel medicine. General advice and medical kit. AB - Physicians must be prepared to provide comprehensive pretravel advice to their patients. Because world conditions are constantly changing, it is necessary to obtain accurate and current information. Common health problems that may be faced by any traveler include accidents, motion sickness, and jet lag. Physicians must familiarize themselves with the many forms of insurance available for the traveler. PMID- 1405819 TI - Immunizations for international travelers. AB - Immunizations for international travel are an important component of pretravel medical care. Travelers should receive protection against vaccine-preventable exotic diseases, and their immunity against common infectious diseases should be reviewed and updated. There are no immunizations for some important infectious hazards of travel. In the course of considering a traveler's risk for exposure to infectious disease on the basis of geographic destination, style of travel, and anticipated activities, the health care provider should discuss preventive measures and personal behavior with regard to food and water, avoidance of insect bites, personal safety, and sexual activity. PMID- 1405820 TI - Special health considerations for travelers. AB - Special health considerations include many issues that affect travelers at both ends of the age spectrum. Pulmonary diseases may seriously alter the physiologic responses to both cabin pressures in commercial airliners and exposure to high altitudes, but many of these responses can be predicted by blood gas determinations and simple measurements of pulmonary function conducted at sea level. Cardiac events represent the most common and unpredictable health problems that threaten both serious morbidity and death for adult travelers. Diabetic travelers require insulin dosage adjustments during east-west travel and well stocked travel kits with adequate supplies. Human immunodeficiency virus-infected travelers require consideration of their levels of immunosuppression at the time of immunizations and special precautions for preventing potentially chronic enteric infections. Young children pose similar questions, and there is the additional problem posed by a limited number of readily available antimalarial agents for pediatric use. PMID- 1405821 TI - The pregnant traveler. AB - The pregnant traveler should seek current and specific advice from experts even if she is traveling to a nearby wilderness area. This advice will make a significant contribution to the safety and health of the pregnant woman and her future newborn. There are many situations, for example, travel to Kenya, the Andes, or the Amazon basin in Peru, where the pregnant traveler is best advised to stay at home, or to defer the trip. PMID- 1405822 TI - Diagnosis, treatment, and prevention of malaria. AB - Optimal treatment of malaria requires rapid case identification, initiation of specific and supportive therapy based on parasitologic and clinical classification of the patient, and recognition of inadequate response to therapy. Health care providers advising travelers should assess the risk of malaria based on itinerary and clinical condition, and counsel to reduce contact with mosquitoes; prescribe appropriate chemoprophylaxis; and counsel regarding potential side effects and requirement for diagnosis and treatment if fever develops. PMID- 1405823 TI - Travelers' diarrhea. Prevention and treatment. AB - Travelers' diarrhea affects almost half of all travelers from developed to developing nations. Its occurrence frequently alters planned activities. Enterotoxigenic Escherichia coli and other bacterial pathogens endemic to the area visited account for the majority of pathogens isolated. Newer research technologies are assisting in defining virulence properties and epidemiologic characteristics. Prudence exercised during travel remains the preferred mode of prevention, reserving antimicrobial prophylaxis for specific situations. Oral rehydration and early pharmacologic intervention with antimicrobial and antimotility agents significantly decrease length of illness when diarrhea occurs. PMID- 1405824 TI - Fever in the returned traveler. AB - Febrile infections can be fatal in travelers to tropical countries unless the patient seeks medical care in a timely manner and the physician takes the time and has the skill to make a rapid diagnosis and prescribe appropriate therapy. In addition to the usual febrile illnesses present in temperate climates, the patient may have an "exotic" infection, e.g., malaria, infectious hepatitis, enteric fever, or dengue fever. The potential causes of fever in travelers are extensive. This article provides practical clues to assist the physician in making the correct diagnosis--by using exposure information, symptoms and signs, and concomitant symptom complexes. PMID- 1405825 TI - Skin problems in returning travelers. AB - A new skin lesion in a returning traveler often poses a difficult diagnostic problem for the clinician whose knowledge of geographic medicine is limited. To reach a diagnosis the physician has to consider the location and style of travel, exposure to pathogens, length of stay, epidemiology, incubation period, and clinical presentation of dermatologic diseases in the countries visited. As with any dermatologic problem, the appearance of the presenting lesion should help to establish the differential diagnosis. This article is a guide to the diagnosis and investigation of skin lesions in returning travelers; it is not intended as a comprehensive review of tropical dermatology. PMID- 1405826 TI - Eosinophilia in travelers. AB - Eosinophilia in travelers may be caused by infections acquired during travels. Infections with helminthic, but not protozoan, parasites are the most likely causes of eosinophilia, although other etiologies may warrant consideration. This article reviews the parasitic and other causes of eosinophilia. Helminthic infections early in their development may elicit the most pronounced eosinophilia yet be difficult to diagnose. Chronic helminthic infections may yield eosinophilia that persists for prolonged periods of time after initial infection. PMID- 1405827 TI - Intestinal parasites in returned travelers. AB - Travelers returning from third-world countries may become infected with a variety of intestinal parasites. Although protozoan infections are more frequently seen, intestinal worms are also encountered. If considered in the differential diagnosis, these infections usually are readily diagnosed and treated. PMID- 1405828 TI - Sexually transmitted diseases and travelers. AB - Sexually active travelers are at risk for a variety of STDs, including traditional venereal infections such as gonorrhea, chlamydial urethritis, syphilis, chancroid, and herpes simplex infection. More recently, hepatitis B, hepatitis C, and HIV-1 have also been described. Risk varies depending on the geographic area of travel and the type of sexual contact. Physicians should be aware of the prevalence of antimicrobial resistance of N. gonorrhoeae and H. ducreyi because this will affect empiric antibiotic therapy. Prevention should focus on proper and consistent usage of barrier contraceptives. PMID- 1405829 TI - Tropical diseases in immigrants and internationally adopted children. AB - Immigrants, particularly those from the developing world, make up a significant number of tropical disease cases seen in a temperate climate. Internationally adopted children are another group in which tropical and other infectious diseases must be considered. The differential diagnoses of various syndromes in these populations in relation to relatively more common tropical diseases are reviewed. PMID- 1405830 TI - High altitude medicine. AB - Altitude illness is common and may result in major disruption of travel plans. Visitors to altitude need to be aware of the various health problems they might encounter and how they may be prevented. Self-diagnosis and treatment is the norm in many remote locations. The hallmark of therapy remains descent, but with newer treatment modalities, this may be easily forgotten. People with preexisting health problems may desire to visit high altitude destinations. It is reasonable to support some strongly motivated people in undertaking such trips, providing they recognize the difficulties of coping with illness in remote locations. PMID- 1405831 TI - An integrated approach for the computer-assisted treatment of diabetic patients on insulin. AB - A prototype computer system has been developed to provide advice on the day-to day adjustment of carbohydrate intake and insulin regimen in the insulin dependent diabetic patient. The system also produces a 24-h simulation of the patient's blood glucose profile based on these adjustments. Advice is generated by a qualitative knowledge-based system which suggests what the next step in improving glycaemic control might be for a given patient, e.g. 'decrease morning short-acting insulin by 2 units'. The quantitative simulator module contains two different mathematical models. The first is a non-linear model in differential equation form which consists of a one-compartment glucose model linked to a model with free and bound insulin compartments. This physiological model is solved by a general-purpose simulation engine. The second is a linear systems model which uses a transfer function to describe the insulin input/blood glucose response relationship for individual diabetic patients. Results of a preliminary medical validation are presented. PMID- 1405833 TI - Telestroika in health care informatics: a challenge for standardization in Europe. AB - This article describes the actual user requirements of the health care sector in connection with telematics. The importance of standardization is stressed. The paper further gives an overview of the current standing of the activities of CEN TC 251 (European Standardization Committee, Technical Committee on Health Care Informatics). PMID- 1405832 TI - Comparison of digital and conventional mammography: a ROC study of 270 mammograms. AB - Observer performance tests were conducted to study the visibility of malignancies in digital mammography. Detectabilities of tumours and of microcalcifications were studied separately. For this purpose two sets of images were used, one for tumours consisting of 150 mammograms and one for microcalcifications containing 120 mammograms. Images were digitized at a resolution of 2048 x 2048 pixels using a 12-bit CCD camera. Conventional film mammograms were read on a lightbox, whereas digital mammograms were viewed on a high-resolution monitor. Two experienced radiologists read both sets independently, and ranked their judgements about the presence or absence of tumours or microcalcifications on a confidence-rating scale. Results were evaluated using receiver operating characteristic (ROC) analysis. No statistical differences were found between judgements based on conventional and digitized mammography. PMID- 1405834 TI - Implications of medical information systems for community health care in Japan. AB - The population of Japan in the 21st century is expected to be distributed heavily on the side of higher ages. In view of the aged society, improved hygienic, medical, and welfare services must be provided in every community. In order to provide these services efficiently it is necessary to implement a community health care system (CHCS). The role and responsibilities of the medical information system, which is intended to support comprehensively the CHCS with respect to providing the necessary information, will become increasingly important. This paper is intended to discuss the structure, features, and required activities of the community medical information system which will have particular importance in the community health care services in the coming years. Problems in establishing and operating future medical information systems in the CHCS also are discussed. Lastly, problems and obstacles confronted when establishing and operating medical information systems in community health care which is organized around the medical association, which plays an important role and takes on heavy responsibility, are discussed, and a proposal is made. PMID- 1405835 TI - Certainty factor theory and its implementation in a medical expert system shell. AB - In this article some topics related to the MYCIN-model for uncertainty handling are discussed. First, it is pointed out that one of the problems identified by Adams should be considered as evidence supporting the point of view that the probabilistic interpretations of measures of belief and measures of disbelief given by Shortliffe are inappropriate. In this context some results achieved by Heckerman are reviewed, and it is shown that similar problems can be identified in the interpretation given by him. It is also pointed out that Heckerman's argument that the original probabilistic interpretation of certainty factors implies non-commutative evidence-updating is not correct. Then, in the context of the result achieved by Horvitz and Heckerman, in which it was proven that there is an isomorphic mapping from the evidence combination scheme for the likelihood ratio to the evidence combination function in EMYCIN and its successors, it is pointed out that the evidence combination scheme for the likelihood ratio suffers from a great restriction on its applicability in expert systems. Subsequently, some short remarks are made with respect to the complaint that sometimes the MYCIN model cannot work as well as expected. Lastly implementation of the certainty factor mechanism in a HIS-oriented expert system shell with some substantial changes is described. PMID- 1405836 TI - A microcomputer-based structured journal system for diseases of the female mammary gland. AB - A medical journal system for female patients with diseases of the mammary gland is described. The system is developed in a commercial database system, and is run by microcomputer. The system has been used for almost 3 years in a department with approximately 550 new patients referred per year. Experience from daily use in patient care, and as a tool for retrieval of medical and administrative data, is reported. Further development of the system is discussed. PMID- 1405837 TI - Automated diagnostic indexing by natural language processing. AB - Developing tools for natural language understanding by computers represents an important and intense field of research. This paper describes a system developed for interpreting medical natural language in the domain of symptoms and diagnoses from complete discharge summaries and locating the correspondent category into the International Classification of Diseases, through indexing by the Systematized Nomenclature of Medicine. The indexing program makes use of the MEID dictionary and some auxiliary semantic databases for identifying adjectival forms, synonyms, hypernyms and other semantic relations while searching for the longest consistent match into SNOMED. A further subdivision of the SNOMED structure was also proposed in order to find the hierarchically superior representative of a conceptual class when this association is not assigned by the related SNOMED code number. The system can be used by any language that possesses a translation of SNOMED and ICD. The knowledge base was built using a conversion file that maps the terms of the nomenclature into the classification, which can be improved by learning from users. PMID- 1405838 TI - New role of a medical documentation system. AB - Architecture of a new medical documentation system (MDS) is proposed. First, we studied the traditional MDS in terms of organizational structure, main functions, means (resources) and personnel. Special emphasis is given to the information retrieval (IR) system which is the kernel of a MDS. Then, some achievements of information technology is summarized, and concept of a mixed IR system which is the kernel of the new system is presented. New architecture is then presented. Units which compose the entire system are: host documentation centre, local documentation centres, and documentation units. Eventually, objective and features of every part are discussed. PMID- 1405839 TI - PACE project: object-orientated modelling of paediatric practice. AB - The need for useful clinical support based on integrated computerized systems is now well recognized. To build systems desired by busy clinicians requires accurate specifications. These specifications in turn require rigorous descriptions of the processes to be automated in a form which is understandable and unambiguous to both clinician and computer scientist. Despite these requirements communication between suppliers and users of computer systems often is poor. Detailed descriptions of health care with particular reference to child health were developed with an object-orientated technique. These descriptions take the form of conceptual models of the basic health care activities (evidence collection, assessing, planning and implementing management) and more specific departmental activities pertaining to paediatric intensive care, accident and emergency, and cystic fibrosis management. We have learned that once a modelling team becomes competent in applying the technique, object-orientated modelling can be a powerful tool for the description of complex processes such as those involved in present-day health care. PMID- 1405840 TI - Basic health care functions: an object-orientated analysis. AB - All clinical activities carried out by health care professionals can be seen as examples of what we have called the basic health care functions. These are collecting information concerning the patient, assessing the patient in the light of the information gathered, and then planning and administering the care which is deemed necessary. For a computerized clinical support system to be helpful to clinicians it is essential that the information and computer scientists responsible for building such systems have clear and detailed descriptions of the activities carried out by their clinical colleagues. One method of bridging this communication gap is object-orientated modelling. In this paper we present an object-orientated analysis of the basic health care functions, thus establishing a generic model on which descriptions of more specific clinical situations can be based. PMID- 1405841 TI - [NO (nitric oxide)--at the threshold of clinical medicine]. PMID- 1405842 TI - [Infant food discount--a good business]. PMID- 1405843 TI - [Psychotherapy instruction--do not ever mix the roles!]. PMID- 1405844 TI - [A radiologist is needed for handling of acute upper gastrointestinal hemorrhage]. PMID- 1405845 TI - [Amoxicillin, drug of choice in otitis]. PMID- 1405846 TI - [Manipulation demands formal training]. PMID- 1405847 TI - [Hair preparation caused fever and clouding of consciousness]. PMID- 1405848 TI - [Fibrinogen as an independent risk factor of cardiovascular disease]. PMID- 1405849 TI - [Glutamine--a non-essential but important amino acid]. PMID- 1405850 TI - [New dosages of flucloxacillin makes therapy of skin and soft tissue infections simpler]. PMID- 1405851 TI - [Evaluations by health insurance authorities. Mental and psychosomatic occupational disorders are slowly increasing]. PMID- 1405852 TI - [The man behind the syndrome. Patrik Haglund, first professor of orthopedics in Scandinavia. A pioneer of rehabilitation who fought for better conditions of the disabled]. PMID- 1405853 TI - [Psychosocial problems must be noticed in rehabilitation after traffic accidents]. PMID- 1405854 TI - [Care in own apartment despite of qualified care needs]. PMID- 1405855 TI - [Heatstroke after a race with serious effects on liver and bleeding status]. PMID- 1405856 TI - [Laparoscopic surgery of perforated duodenal ulcer]. PMID- 1405857 TI - [Acute abdomen in a swimmer was caused by abdominal wall hematoma]. PMID- 1405858 TI - [The pediatric hospital Samariten--an autonomous health care unit in Stockholm 1890-1974]. PMID- 1405859 TI - [Moral contribution?]. PMID- 1405860 TI - [Mushroom poisoning--an unavoidable phenomenon?]. PMID- 1405861 TI - [Vitamin B 12 deficiency--even a neuropsychiatric problem]. PMID- 1405862 TI - [Therapeutic instruction and jurisprudence]. PMID- 1405863 TI - [Clean up in the borderline swamp]. PMID- 1405864 TI - [Health personnel's knowledge of treatment with nebulizers is insufficient]. PMID- 1405865 TI - [Sex hormone binding globulin--a new dimension of androgenic diagnostics]. PMID- 1405866 TI - [Pharmacological treatment of heart failure]. PMID- 1405867 TI - [Effect on plexus in laparoscopic surgery--a complication which could be avoided]. PMID- 1405868 TI - [Acute renal failure caused by mushroom poisoning with Cortinarius speciosissimus]. PMID- 1405869 TI - [A new effective therapeutic method in bleeding esophageal varices]. PMID- 1405870 TI - [Is there any future for private practitioners?]. PMID- 1405871 TI - [Postoperative pain relief--agents, methods, benefits and organization]. PMID- 1405872 TI - [Is prevention of hypertension possible?]. PMID- 1405873 TI - [Vagitrim--a new, simple aid for effective training of pelvic floor muscles]. PMID- 1405874 TI - [Marked increase of hospitalization for alcoholism and narcotic abuse]. PMID- 1405875 TI - [No symptoms of unnecessary anxiety or false confidence among participants of screening for malignant melanoma]. PMID- 1405876 TI - [Patient-controlled analgesia after major back surgery]. PMID- 1405877 TI - [An inquiry on antibiotic prevention in surgery: preparations, dosage, duration of treatment vary widely]. PMID- 1405878 TI - [Constant annual incidence of HIV infection among intravenous drug addicts]. AB - Since January 1987 a study of HIV prevalence and risk behaviour among i v drug abusers at the remand prison in Stockholm has been carried out by a research team working independently of the penal system. On a voluntary basis, a standardised interview is carried out and an HIV blood test made. Of the 2,038 i v drug abusers who participated up to December 1991, ten per cent were HIV-positive. Of the 80 per cent who mainly used amphetamines, six per cent were seropositive, as compared with about 28 per cent of the remaining 20 per cent who were heroin addicts. The overall annual incidence of HIV infection was about one per cent. The cumulative prevalence decreased among heroin users during the observation period, but remained constant among amphetamine users. The frequency of injection equipment sharing showed a decline at the beginning of the observation period, but the level of sexual risk behaviour has remained high. PMID- 1405879 TI - [The obsessive-compulsive syndrome: new aspects of a psychiatric chameleon]. PMID- 1405880 TI - [A pilot study: neuropsychological rehabilitation of patients with solvent induced toxic encephalopathy]. AB - Fourteen patients with chronic toxic encephalopathy underwent a neuropsychological intervention comprising crisis therapy, information about the disease, and cognitive training. Evaluation showed the patients to have experienced substantial improvement in their daily life and family relations as a result of the intervention. Their affective symptoms decreased and their verbal memory improved. Regional cerebral blood flow (rCBF) measurements showed training dependent changes of functional activity related to change in memory strategy. This rCBF change had disappeared six months later, however, suggesting that the duration of intervention needs to be extended in order for use of the learned memory techniques to become automatic. We conclude that neuropsychological rehabilitation is effective and should be made available to patients with chronic toxic encephalopathy. PMID- 1405881 TI - [Anti-shock trousers--therapeutic complement in severe obstetric hemorrhage]. PMID- 1405882 TI - [Plausible anamnesis was an incidental finding]. PMID- 1405883 TI - [Acute cerebellar degeneration was a para-malignant phenomenon]. PMID- 1405884 TI - [Myasthenia gravis in patients with ulcerative colitis--an overlooked autoimmune association?]. PMID- 1405885 TI - [The man behind the fracture. Abraham Colles--one of Ireland's greatest surgeons. He treated distal radius fractures without the slightest postoperative defect or deformity]. PMID- 1405886 TI - [Activities of the Balint group--continuous education for more effective care]. PMID- 1405887 TI - [Female circumcision--a humiliation with deep cultural roots]. PMID- 1405888 TI - [Must psychiatry sell its soul?]. PMID- 1405889 TI - [Light and biological rhythms]. PMID- 1405890 TI - [Is amalgam in dental fillings hazardous to health?]. PMID- 1405891 TI - [Intestinal tuberculosis. Simple treatment can prevent unnecessary surgery]. PMID- 1405892 TI - [Thromboangiitis obliterans--an often overlooked disease with increasing incidence]. PMID- 1405893 TI - [Axillary temperature measurement is not reliable in newborn infants]. PMID- 1405894 TI - [The PAD result is of little significance for treatment of gallbladder cancer]. PMID- 1405895 TI - [Prognosis and treatment of symptomatic hyponatremia--a study of 28 intensive care cases]. AB - In symptomatic cases of hyponatraemia, where the serum sodium concentration is less than 115 mmol/l, prognosis has hitherto been considered to be poor, and mortality rates of 50 per cent have been reported. The management of this condition is controversial, particularly concerning the optimal rate of correction, correlations having been reported between the occurrence of central pontine myelinolysis and both over-correction and too rapid correction. During the 3-year duration of the study reported in the article, of 28 cases with a mean sodium concentration of 106 mmol/l, the outcome was fatal in only one case. In both of the only two cases of acute hyponatraemia (i.e., developing within 24 hours), correction had been rapid (mean rate 2.6 mmol/l per hour). In the remaining 26 cases correction of chronic hyponatraemia was slower (mean rate 0.6 mmol/l per hour), adjustment to a slightly hyponatraemic level having been achieved with isotonic saline (N = 25) or water restriction (N = 1). The findings in the study suggest that, provided that the rate of correction is not too rapid, the prognosis in cases of severe symptomatic hyponatraemia is more favourable than previously reported. PMID- 1405896 TI - [A survey in Malmo. The frequency of venous thromboembolism has not changed during the last 30 years]. PMID- 1405897 TI - [Postcoital contraception, a forgotten and unused resource?]. PMID- 1405898 TI - [Intestinal tuberculosis--still a clinical reality]. PMID- 1405899 TI - [Autotransfusion of blood cells made surgery of a Jehovah's Witness possible]. PMID- 1405900 TI - [Unusual cases and diagnoses are not rare at orthopedic emergency departments during weekends]. PMID- 1405901 TI - [Routine preoperative cholangiography in cholecystectomy: to be or not to be?]. PMID- 1405902 TI - [Quality assurance--next step must be from words to action]. PMID- 1405903 TI - [Increasing introduction of magnetic resonance tomography in county hospitals]. PMID- 1405904 TI - [Advanced analysis and concern for care programs are signs of current medical decision theory in the USA]. PMID- 1405905 TI - [Consultation--the most important working tool of general practitioners]. PMID- 1405906 TI - [The "helicopter perspective" of health care makes effective rationing more difficult]. PMID- 1405907 TI - [Do not change maternal health services for the worse]. PMID- 1405908 TI - [Garlic as cultural historical medicinal plant--truth or superstition?]. PMID- 1405909 TI - [Subjective illness in non-malignant chronic pain--working patients are feeling better than sick-listed patients]. PMID- 1405911 TI - [Discitis in children imitates acute abdomen and misleads diagnosis]. PMID- 1405910 TI - [Neurosarcoidosis can occur without any other signs of sarcoidosis]. PMID- 1405912 TI - [Give antibiotics prior to computer tomography if meningitis is suspected]. PMID- 1405913 TI - [Sore throat was a foreign body]. PMID- 1405914 TI - [Good primary care can give support and help to severely ill/dying children and their families]. PMID- 1405915 TI - [Psychodynamic and cognitive therapy in the same course--more extended education with good results]. PMID- 1405916 TI - [Unified AT test with a guaranteed supervision improve education]. PMID- 1405917 TI - [The church and health care--no deep gap]. PMID- 1405918 TI - [Molecular biology completes clinical chemical methods in investigation of hemoglobin diseases]. PMID- 1405919 TI - [Penicillin V and not amoxicillin is the first choice preparation in acute otitis]. PMID- 1405920 TI - [Fertilization in vitro should be seen as a therapeutic alternative]. PMID- 1405922 TI - ["When throats are visiting...." A profitable business for a rapid test?]. PMID- 1405921 TI - [Ridiculously small achievements in earlier programs aimed to change life style of persons with hypertension]. PMID- 1405923 TI - [Is the general practitioner dangerous for warfarin-treated patients?]. PMID- 1405924 TI - [Special training of neck extension strength can be effective in treatment of neck problems]. PMID- 1405925 TI - [Postnatal care of hydronephrosis after prenatal diagnosis]. PMID- 1405926 TI - [Long-term counseling supports HIV-positive immigrants]. PMID- 1405927 TI - [The man behind the narcosis. Crawford Long--the man behind ether narcosis. He was threatened by lynching when performing painless surgery]. PMID- 1405928 TI - [Tumor suppressor genes: mutations in RB and p53 genes are significant carcinogenic factors]. AB - The RB and p53 tumour suppressor genes encode nuclear proteins that exert an inhibitive effect on cell growth. A large variety of human tumour types manifest loss or mutation of the RB or p53 genes, and p53 mutation is the commonest genetic alteration found in tumour cells. In addition, the RB and p53 proteins may be inactivated by complex formation with viral oncoproteins--for instance, in the case of cervical carcinoma carrying human papilloma virus. In vivo introduction of an intact RB or p53 gene into malignant cells lacking the respective gene results in suppression of the neoplastic phenotype and thus of tumourigenicity, p53 being the more potent of the two in this respect. Further elucidation of tumour suppressor genes may well result in future improvement in the diagnosis and treatment of cancer. PMID- 1405929 TI - [Increasing number of hemoglobinopathies. Rapid diagnosis with DNA technique]. PMID- 1405930 TI - [Postpoliomyelitis syndrome--additional functional disturbances in persons suffering of poliomyelitis]. PMID- 1405931 TI - [Pancreatic resection in cancer: surgical results are better today]. PMID- 1405933 TI - [Decentralized coronary care program: better quality of care and shorter waiting lists when angiography and vascular surgery are performed locally]. PMID- 1405932 TI - [Regional hyperthermic perfusion has impressive effect on manifest malignant melanoma]. PMID- 1405934 TI - [Regional centers provide health services with problem-oriented drug information]. PMID- 1405935 TI - [Traumatic stress. Increased knowledge of post-traumatic stress syndrome is necessary for care of refugee children]. PMID- 1405936 TI - [Pneumonia--a source of error in the cause of death statistics]. PMID- 1405937 TI - [Bad economic management--the cause of explosion of health care costs]. PMID- 1405938 TI - [Can the structural formula of a drug verify the risk of contact allergy?]. PMID- 1405939 TI - [Markers in alcoholism]. PMID- 1405940 TI - [General vaccination against Haemophilus influenzae type b--unified decision for the entire country is needed]. PMID- 1405941 TI - [Insist on high standards of personnel working with manipulation therapy]. PMID- 1405942 TI - [A study on reflux esophagitis--clinical nonsense]. PMID- 1405943 TI - [Treatment of rapists requires cooperation]. PMID- 1405944 TI - [A new test in for alcohol diagnosis. Carbohydrate-deficient transferrin is an efficient marker for detection of prolonged abuse]. PMID- 1405945 TI - [Laparoscopic cholecystectomy--a new method worth to be established]. PMID- 1405946 TI - [Traumatic stress. Combat reactions and post-traumatic stress. The war is not over when peace is declared--it is still alive in people's minds]. PMID- 1405947 TI - [Ask concrete questions on life habits when diagnosing dyspepsia!]. PMID- 1405948 TI - [Careful anamnesis and differential diagnosis: guide to the treatment of dyspepsia]. PMID- 1405949 TI - [How do we solve the conflict of interest between the pregnant woman and her fetus?]. PMID- 1405950 TI - [Results of selective proximal vagotomy after 13 years]. AB - This study reports the long-term results of 216 patients after highly selective vagotomy (HSV) for duodenal ulcers operated from 1970 through 1978 with a mean follow-up of 12.8 years (8.3-15). 26 patients developed symptomatic ulcer recurrences (12%) within 4 to 135 months following surgery, the cumulative recurrence rate (Kaplan-Meier) at 13 years was 20.3%. Acidity analyses showed a postoperative mean reduction of basal acid output (BAO) and maximal acid output (MAO) values of 80.7% and 74.8% respectively with no differences according to recurrences. The risk of recurrence was similar for duodenal (22/194) and pyloric ulcers (4/22) and no differences were found with respect to sex, additional drainage procedure, smoking habits, acute or elective operation and first or recurrent ulcers. Risk was slightly higher for complicated ulcers (p less than or equal to 0.07), but without reaching statistical significance. 78.5% of patients showed (very) good results (Visick I or II), only 6% were Visick III. HSV is therefore regarded as a valuable therapeutic measure for the treatment of duodenal ulcer independent of patient compliance. PMID- 1405951 TI - [Preventive or therapeutic parathyroidectomy in primary hyperparathyroidism]. AB - The only causal treatment of primary hyperparathyroidism (PHPT) is parathyroidectomy. There are indications in the literature that despite operation expectation of life is shortened because of an increased frequency of cardiovascular and malignant diseases leading to the recommendation for early surgery even in uncomplicated PHPT. It is easier to convince an asymptomatic patient of an operation when he is informed about complications and consequences of an expectative attitude. Therefore, we reviewed our 71 patients operated upon during a 4-year-interval, 58 of whom were followed-up. During 82 operations 115 pathologically altered parathyroid glands were removed. Two persistent paralyses of the recurrent nerve occurred, however, without alteration of the voice. Follow up of 82% of patients revealed 2 cases of recurrent nephrolithiasis (1 hypercalcaemia, 1 normocalcaemia). Three (5%) true recurrences were found, but neither a pancreatitis nor a peptic ulcer was noted during long-term follow-up. None of the 137 patients operated for a bleeding or perforated peptic ulcer during the last 10 years and 1 of 55 patients with acute pancreatitis during the past 8 years suffered from a PH-PT. However, morbidity and mortality of these two conditions was high. Although correlation to PHPT was low we recommend early operation of PHPT because of the low morbidity rate, zero lethality and reduced expectation of life. PMID- 1405952 TI - [Endoscopic therapy of benign anastomotic stenoses in the area of the colon and rectum by electro-incision and balloon dilatation]. AB - 21 patients with a severe anastomotic stenosis in the colorectal region were treated with hydraulic balloon dilatation and endoscopic electro-incision. The severity of symptoms directly correlates with the extent of stenosis (degree I phi 13 mm, n = 12; degree II phi 7 mm, n = 6; degree III phi 4 mm, n = 3). All patients with a stenosis of degree I and II were symptom-free after the endoscopic therapy. In 2 of 3 cases the symptoms of stenosis of degree III could clinically be improved after the treatment. The average frequency of dilatation was 1.5 x, complications such as bleeding or perforation were not registered. Animal studies explain anastomotic stenosis through an increased submucosal formation of collagen fibers followed by formation of scars in the anastomosis. The efficiency of electro-incision and balloon dilatation is based on an increased diameter in the anastomotic region without increased formation of new collagen fibers. PMID- 1405953 TI - [Resection of esophageal cancer without thoracotomy by manual dissection and eversion stripping]. AB - At the department of surgery of the university of Cologne-Lindenthal, 184 patients (142 with squamous cell carcinoma of the esophagus, 42 with adenocarcinoma of the gastroesophageal junction) underwent blunt dissection of esophageal cancer between 1983 and 1991. Tumor expansion classified by the pathologist was stage I in 13.6%, stage II in 31.0%, stage III in 41.8%, and stage IV in 13.6% of all cases. Histological tumor differentiation was graded well in 4.3%, moderate in 71.7%, and poor in 19.6%. Principally a gastric tube was used for esophageal replacement (96.3%), while interposition of the large bowel was performed in 5 cases. All the patients were prospectively monitored for perioperative complications. 64.7% fared without any complications intraoperatively. The most frequent intraoperative complications were damage of the pleura parietalis (16.3%), rupture of the tumor during dissection (13.0%), and lesion of the spleen (11.4%). 29.9% of the patients had a postoperative course without any complications. Pleural effusion (38.6%) and insufficiency of the cervical anastomosis (22.8%) were the most frequent complications seen postoperatively. Hospital mortality amounted to 6.0%. Six months after the operation most patients deemed their quality of life satisfying or excellent, respectively. The cumulative survival rate (without hospital mortality) was 78.3% after the first year, 24.7% after the third year and 20.6% after the fifth year. PMID- 1405954 TI - [Anterior and posterior rectopexy with levator repair in patients with rectal prolapse and incontinence]. AB - A prospective clinical, manometric and radiological study has been performed, before and after rectopexy, on 18 female patients with complete rectal prolapse, and varying degrees of incontinence. All patients, mean age 62 years, underwent anterior-posterior fixation (Ivalon or Vicryl) of the rectum with posterior pelvic repair of the puborectalis muscle. 13 patients with obstipation and rectal prolapse were treated by rectopexy combined with sigmoidectomy. Postoperatively there was a significant increase in the resting anal pressure and maximum voluntary contraction pressure (p = 0.01). Continence was improved in 16 patients (89 percent), 9 (56 percent) of whom regained normal continence. No significant change in pelvic descent or anorectal angle was seen postoperatively. Following abdominal rectopexy and resection obstipation was reduced in 9 of 13 patients (70 percent). PMID- 1405955 TI - Interbody fusion of the lower cervical spine: a dangerous surgical method? AB - Our follow-up study of 175 cases of interbody fusion of the lower cervical spine was conducted to show the complications that occurred in our department with what is considered to be a tried and tested method. From 1976 to 1990, 175 patients were treated with this method. These 175 cases included 150 fractures and/or dislocations. The indications for surgery in the remaining 25 cases were tumors and metastases, inflammatory or degenerative diseases and chronic instabilities following laminectomy. The following complications were seen: 4 cases of infection, 3 postoperative redislocations, 2 cases of extensive loosening of metal, 1 unilateral lesion of the vertebral artery, 1 nonunion with plate fracture, 1 post-operative radicular disorder in an otherwise neurologically normal patients, and 1 secondary extension of the interbody fusion required after failure to recognize a two-segment lesion. PMID- 1405956 TI - [Holmium:YAG and erbium:YAG infrared laser osteotomy]. AB - The in-vivo bone ablation characteristics of a pulsed solid-state erbium:YAG laser were compared to those of a pulsed solid-state holmium:YAG laser. Partial osteotomies in the maxillary, the mandibulary, and the nasal bones of white rats were performed. The tissue response was examined by light microscopy. Thermal gradients following the laser application were also measured. Over all energy levels tested the erbium:YAG laser produced ablation of bone with minimal thermal damage to the adjacent tissue. The results of this study are promising for future application of the infrared holmium- and erbium:YAG lasers in otorhinolaryngology. PMID- 1405957 TI - [Treatment of peritonitis with staged lavage: prognostic criteria and course of treatment]. AB - In order to define rational criteria for "planned relaparotomies" (PR) in the treatment of critical intra-abdominal infections we have analysed characteristics and the clinical course of 377 patients with diffuse peritonitis 152 of whom were treated by PR. More detailed prognostic aspects and data of the clinical course were prospectively investigated in 111 cases. Patient's age and an underlying malignoma revealed to be of prognostic significance in both univariate and multivariate analysis. The number of organs involved in septic organ failure during the treatment was a further indicator of risk. 40% of our patients, however, survived even an impairment of 5 organ-systems. The successful eradication of the source of peritonitis either with the 1st operation or only with consecutive operations resulted in a crucial difference of the mortality rate with 14% and 64% respectively. The failure to accomplish a definite operative resolution was accompanied by a mortality rate of 90%. The systematical application of PR facilitated control and completion of the eradication of the source of peritonitis. In one third of the patients treated by PR this technique led to early detection of relevant complications and adequate operative treatment. Patients in whom primarily a definitive eradication of the source of peritonitis had been accomplished did not benefit from PR. In patients with persisting or relapsing peritonitis, however, PR was accompanied by a 27% reduction of mortality. PMID- 1405959 TI - [Does laparoscopic appendectomy still have value in acute appendicitis?]. PMID- 1405958 TI - [Consequences of routine gastroscopy before cholecystectomy]. AB - In a retrospective study of 610 patients the role of routine gastroscopy prior to cholecystectomy was investigated. The results demonstrated that only in a low incidence (11% of patients gastroscopied) relevant findings are present. However, most of these patients had a typical history. Therefore, despite risks, routine preoperative endoscopy prior to cholecystectomy should be performed only in patients with a history of upper abdominal pain or discomfort. PMID- 1405960 TI - Posttympanostomy otorrhea: the efficacy of canal preparation. AB - Otorrhea is the most common posttympanostomy complication. This study is designed to determine the efficacy of canal preparation prior to tympanostomy tube placement. One hundred thirty ears were prospectively randomized into prepared (Betadine and alcohol) and nonprepared (control) groups. Cultures obtained before, during, and after preparation were analyzed to determine the external canal flora and effectiveness of sterilization. Prepared ears and nonprepared control ears were examined for relation to otorrhea. Forty percent of the canals were sterile before preparation, and only 8% harbored suspected pathogenic organisms. Canal preparation successfully sterilized only 33% of the ears that contained bacteria. There was no difference in the otorrhea incidence among treatment groups (9.8%). Based on these bacteriologic and clinical findings, it is concluded that canal preparation with Betadine and alcohol does not reduce posttympanostomy otorrhea. PMID- 1405962 TI - H-Index: a new measure of glottal efficiency for the pathologic voice. AB - Taking advantage of the extended dynamic range of digital analysis of voice the H Index represents the first proposed acoustical measure of glottal efficiency. "Hi" /hai/ was chosen to evaluate glottal efficiency since it provides an excellent test of glottal transformation from voiceless to voiced sound energy, the upper vocal tract having a neutral effect. Fifteen individuals with normal voices and 30 patients with hoarse voices were asked to say "hi." The power ratio of /h/ to /a/ was calculated from peak power of each measure from the power envelope. Voice quality had a highly significant effect on measured values (P < .001). A high degree of correlation (P < .001) was found with the AC/DC ratio, a standard aerodynamic measure of glottal efficiency. The results indicate that the H-Index represents an excellent measure of glottal efficiency, obviating the need of invasive techniques or expensive, highly specialized equipment. PMID- 1405961 TI - Analysis of the efficiency of retrocochlear screening. AB - The auditory brainstem response (ABR), as well as associated audiologic and radiographic studies of 175 patients suspected of having cerebellopontine angle tumors were reviewed. The majority of patients presented with asymmetric hearing loss. Eight acoustic neuromas were identified. All eight had abnormal ABRs. The false-positive rate was 22%. Rollover and acoustic reflex testing played a minimal role in the decision as to whether or not an ABR was ordered and, as a result, are not important in the search for retrocochlear disease. The cost per tumor diagnosed was roughly $7600. A rational approach to tumor screening based on the efficiency and cost of the screening tests, the frequency of abnormal ABRs, and the cost per tumor diagnosed is presented. PMID- 1405963 TI - Time series analysis of glottal airflow in normal and pathological phonation. AB - Time series analysis of glottal airflow was carried out on 26 normal controls and 40 patients with voice disorders, using a modification of Isshiki's original technique which uses a hot-wire flowmeter, taking cycle-by-cycle fluctuations into consideration. The mean flow rate and mean AC/DC were shown to have significant differences among normal and patient groups. The standard deviations of AC/DC and AC/DC perturbation were calculated from the AC/DC value of 50 cycles and shown not to vary significantly among the normal and patient groups. The relationship between AC/DC and perceptual impression of voice was also studied among 20 selected patients with breathy voices. Using Spearman's rank correlation coefficient, this relationship was found to have statistical significance (P < .05). PMID- 1405964 TI - Treatment of hemangiomas of the head and neck. AB - Hemangiomas are a group of pediatric tumors that present at or soon after birth. Rapid proliferation is seen in the neonatal period, and may continue for the first year of life. Involution follows, and may last as long as 12 years. Since hemangiomas invariably involute, the vast majority have been left untreated. At least 10% to 20% of cases, however, will need active intervention, traditionally in the form of oral Prednisone. The frequent occurrence of life-threatening complications, permanent deformities, and irreversible psychosocial damage in spite of adequate steroid therapy necessitated a fresh look at the management of these lesions. Using recently developed laser technology alone or in combination with surgical excision, the authors have developed guidelines for safe intervention in all stages of the hemangioma cycle. Safe, active intervention in accordance with these guidelines offers an alternative to the more conservative approach previously advocated. PMID- 1405965 TI - The effect of unilateral and bilateral nasal obstruction on snoring and sleep apnea. AB - The purpose of this study was to compare apnea and snoring in patients with different patterns of nasal resistance: normal, high unilateral, and high bilateral. The authors examined 683 unselected patients referred for evaluation of snoring and possible sleep apnea. All patients had determination of nasal resistance (performed during wakefulness in the seated posture) and nocturnal polysomnography including quantitative measurement of snoring. Analysis of variance showed no significant difference in apnea and snoring indices among the three nasal resistance groups (normal, high unilateral, and high bilateral). Furthermore, there was no significant difference in the frequency of patients with different severity of apnea and snoring among the three groups. It is concluded that 1. unilateral and bilateral elevation of nasal resistance may lead to equally severe snoring or apnea; 2. there is no direct relationship between awake seated nasal resistance measurement and sleep disordered breathing; and 3. measurements of supine nasal resistance during sleep may be required to elucidate the relationship between sleep-disordered breathing and nasal obstruction. PMID- 1405966 TI - Preservation of hearing and facial nerve function in resection of acoustic neuroma. AB - The surgical results in 78 recent cases of total removal of unilateral acoustic neuroma in which an attempt was made to preserve cochlear function have been added to the authors' previous series of 66 cases to evaluate the factors influencing the ability to preserve useful hearing. Useful hearing was defined by speech reception threshold no poorer than 70 dB and a discrimination score of at least 15%. Analysis using a logistic regression model showed that certain preoperative clinical parameters such as tumor size, speech discrimination score, and gender were significantly correlated with hearing outcome. Favorable outcome was significantly correlated with smaller tumor size, higher preoperative speech discrimination score, and male sex. From this data, an explicit formula was devised for predicting hearing outcome for an individual patient. In four cases with useful hearing preserved, there was improvement of greater than 15 percentage points in speech discrimination scores. While preoperative auditory brainstem responses were not predictive of hearing preservation, monitoring of intraoperative auditory evoked potentials was predictive of hearing outcome in selected cases. Specifically, when wave V was unchanged at the end of the operation, even if it may have been transiently lost during surgery, useful hearing was invariably preserved. PMID- 1405967 TI - Three-dimensional surgical anatomy for stapes surgery computer-aided reconstruction and measurement. AB - To define anatomical relationships relevant to stapes surgery, computer-aided three-dimensional reconstruction and measurement were performed on nine normal temporal bones. The mean distance from the inferior portion of the long process of the incus to the center of the oval window was 3.80 mm. The shortest distance from the center of the oval window to the utricular macula, saccular membrane, and macula averaged 1.37, 1.60, and 2.13 mm. Surgery directed posteromedial superior from the oval window was found to be most dangerous because it would come so close to the utricular macula; a posteromedial-inferior approach was found to be safest. The distance from the inferior margin of the oval window inferiorly to the cochlear duct in the hook portion ranged between 0.58 and 1.29 mm, suggesting that when a drill hole is made on the inferior margin of the oval window to lift up a depressed stapes footplate, the hole should not be greater than 0.5 mm in diameter. PMID- 1405968 TI - Some forms of tinnitus may involve the extralemniscal auditory pathway. AB - It has previously been shown that the click-evoked responses recorded from the intracranial portion of the eighth nerve in patients with incapacitating tinnitus are not abnormal, nor is the latency of peak III of the click-evoked brainstem auditory-evoked potentials significantly altered; however, the latency of peak V is slightly (but significantly) shortened in comparison to that of patients with the same degree of hearing loss but no tinnitus. In this study the hypothesis that the extralemniscal auditory system is involved in the generation of tinnitus is tested. We made use of the fact that neurons of the extralemniscal auditory system also receive input from the somatosensory system, and that stimulation of the somatosensory system can influence the processing of auditory information in the extralemniscal system. In 4 of 26 patients with mild-to-severe tinnitus whose median nerve was stimulated electrically, the tinnitus increased noticeably during stimulation, in 6 the intensity of the tinnitus decreased noticeably, and in the remaining 16 there was no noticeable change in the tinnitus. In some of the patients the character of the tinnitus changed in a complex way. There were no significant differences in hearing thresholds in these three groups of patients. Electrical stimulation of the median nerve in 12 individuals with normal hearing who did not have tinnitus either had no effect on the loudness of sounds or it caused a slight increase in the loudness. PMID- 1405969 TI - Facial nerve to facial canal cross-sectional area ratio in children. AB - The incidence of facial palsy among children is lower than that among adults, and the recovery rate after facial palsy among children is higher than that of adults. To investigate these differences, we compared the cross-sectional area ratio of the facial nerve to that of the facial canal in 26 pediatric temporal bone specimens with that of 10 adult temporal bone specimens. The ratios were 0.31 +/- 0.08, 0.35 +/- 0.10, and 0.18 +/- 0.12, respectively, in the labyrinthine, horizontal, and mastoid segments of pediatric specimens. The ratios for adult specimens were 0.46 +/- 0.07, 0.52 +/- 0.17, and 0.37 +/- 0.04, respectively, in the labyrinthine, horizontal, and mastoid segments. These ratios were all significantly smaller than those for the corresponding segments of the adult specimens (P < .01). The results indicate that in children there is less possibility for entrapment of the facial nerve in the facial canal, and that children require facial nerve decompression less often than adults. PMID- 1405970 TI - Holmium:yttrium aluminum garnet laser-assisted endoscopic sinus surgery: clinical experience. PMID- 1405971 TI - Anatomic guidelines for dacryocystorhinostomy. PMID- 1405972 TI - Gore-Tex implants: applications in facial paralysis rehabilitation and soft tissue augmentation. PMID- 1405973 TI - Endotracheal tube stabilization. PMID- 1405974 TI - Annular wedge tympanoplasty. PMID- 1405975 TI - Gelfilm myringoplasty. PMID- 1405976 TI - Gelfilm myringoplasty. PMID- 1405977 TI - Implantable bone conduction hearing device. PMID- 1405978 TI - S-100 protein in human inner ear. PMID- 1405979 TI - Defect reconstruction and cerebrospinal fluid management in neurotologic skull base tumors with intracranial extension. AB - Intracranial extension (ICE) is the spread of tumor into the subarachnoid space through dura or along cranial nerve roots. The single-stage removal of the skull base tumor with its ICE has been confounded by cerebrospinal fluid management and defect reconstruction. The purpose of this report is to review a current protocol for managing the cranial base tumor and its ICE as a unit. The ventricular shunting paper of 1987 is retracted. All tumors were managed at a single stage. Defect reconstruction was size dependent. Ninety-eight neurotologic skull base tumors with ICE were managed from 1971 to 1991. The new protocol was initiated in 1987. Results specific to this group are highlighted. For glomus tumors, cerebrospinal fluid leak rates have been dramatically reduced overall from 14.5% to 4%. The leak rates for nonglomus tumors, overall, have improved slightly. Complications are discussed. The development of this surgical approach protocol improves the functional outcome in patients of surgeons who aspire to disease "cure" rather than "control." PMID- 1405980 TI - Frontal sinus fractures in the pediatric population. AB - Full development of the frontal sinus is not achieved until approximately 19 years of age. An evaluation of frontal sinus injuries isolated to the subset of patients less than 20 years old has yet to be reported. In order to determine whether age was a factor in the clinical course of patients with frontal sinus fractures, 209 patients who sustained frontal sinus fractures from January 1985 to April 1990 were identified using the trauma registry from all six major trauma centers, one of which is a pediatric trauma center, in a county of 2.5 million people. Forty patients (19%) were between the ages of 6 and 19 years at the time of their injury. Computed tomography imaging of these pediatric patients identified associated head and neck fractures in 37 (93%) as well as significant central nervous system injury in 22 (55%). Seventeen pediatric patients were treated nonoperatively and 1 died prior to the planned surgery. A detailed analysis of extent of injury and treatment together with a comparison of the 169 adult and the 40 pediatric patients is presented. PMID- 1405981 TI - Electrical promontory stimulation in patients with intact cochlear nerve and anacusis following acoustic neuroma surgery. AB - Anacusis following hearing preservation surgery for acoustic neuroma removal in which the cochlear nerve was preserved has been explained on the basis of neural or vascular compromise. In the absence of pathologic evidence for either theory, a physiologic model was chosen. Electrical promontory stimulation with monitoring of subjective and electrically evoked auditory brainstem responses was undertaken. A positive response to stimulation suggests a vascular impairment of the cochlea sparing the cochlear nerve and spiral ganglion. The absence of response suggests loss of neural integrity at the level of the spiral ganglion or cochlear nerve. Six patients who suffered anacusis following hearing preservation surgery for acoustic neuroma were studied. Data regarding electrical promontory stimulation, auditory brainstem responses, and implications of the possible role of cochlear implantation are discussed. PMID- 1405982 TI - Temporal bone histopathology in chronically infected ears with intact and perforated tympanic membranes. AB - Chronic suppurative otitis media has been clinically defined as a chronic discharge from the middle ear in the presence of a perforation of the tympanic membrane. However, irreversible tissue pathology in the middle ear or mastoid can occur behind an intact tympanic membrane. One hundred forty-four human temporal bones with chronic otitis media were divided into two groups: those with perforated (28) and those with nonperforated (116) tympanic membranes. The histopathological findings of their middle ears were compared. Granulation tissue in various degrees was the most prominent pathological feature. It was observed in 96% of temporal bones with perforation of the tympanic membrane, and in 97% of those without perforation. Also found were ossicular bony changes (96% with perforation; 90.5% without), middle ear effusion (93% with perforation; 89% without), cholesterol granuloma (21% with perforation; 12% without), cholesteatoma (36% with perforation; 4% without), and tympanosclerosis (43% with perforation; 20% without). This study shows that the histopathological changes of the middle ear are similar in temporal bones with and without perforation of the tympanic membrane. The clinician should, therefore, be aware that an intact tympanic membrane does not necessarily preclude the presence of gross pathological changes of the middle ear cleft. PMID- 1405983 TI - A canine model for studying laryngospasm and its prevention. AB - Laryngospasm, if prolonged, can result in serious sequelae due to the lack of a uniformly effective treatment. Prevention, therefore, through pharmacologic intervention, is an attractive concept. In order to study the effects of various drugs in preventing laryngospasm, a reliable animal model capable of producing sequential, repetitive episodes of laryngospasm is necessary. In this study, the canine model of laryngospasm previously described by Aviv, et al. was modified to overcome technical factors which limited its use in this regard. Details of the technique and the results from eight animals will be presented. Results in two animals with the use of prophylactic topical lidocaine will also be discussed. The reliability and reproducibility of this model make it ideal for the study of laryngospasm and open the way for investigation into its prevention. PMID- 1405984 TI - Sucralfate in alleviating post-tonsillectomy pain. AB - Tonsillectomy results in severe throat pain, ear pain, and trismus until the exposed and inflamed muscle becomes covered with regenerated mucosa. Sucralfate binds with the fibrinous exudate of duodenal ulcers, forming a protective barrier that promotes healing. If a similar buffer could be created in the tonsillar bed, morbidity may be diminished. A double-blind, randomized study was completed in 34 adult patients to determine whether sucralfate, given four times daily for 10 days as a swish and swallow, would significantly reduce postoperative pain and promote healing and recovery. Sucralfate significantly lowered postoperative throat pain, otalgia, and trismus. Sucralfate is a safe and well-tolerated topical agent that offers significant pain reduction and may promote healing in tonsillectomy patients. PMID- 1405985 TI - Association of skull base and facial fractures. AB - A retrospective analysis of 268 trauma patients with facial fractures who received computed tomography of the head was undertaken to assess an association with skull base fractures. The incidence of skull base fracture was compared to facial fractures of various anatomic locations. Skull base fractures were significantly increased in orbital wall/rim fractures (36.0%, P = .0823). In contrast, skull base fractures related to orbital floor (27.3%, P = .6191) and maxillary/zygomatic (29.4%, P = .1148) fractures were not significantly greater and were infrequently seen with mandible (4.0%, P = .0454) and nasal (7.7%, P = .0345) fractures. The incidence of skull base fracture was directly associated with the number of facial fractures per patient; one facial fracture (21.0%), two facial fractures (30.4%), and three or more facial fractures (33.3%) (P < .05). The incidence of skull base fractures was related to the location of facial fractures and the number of facial fractures per patient. The results provide additional clinical information to facilitate the prompt detection and diagnoses of skull base fracture. PMID- 1405986 TI - Infant botulism: considerations for airway management. AB - Infant botulism is a national problem with over 1000 confirmed cases in the United States since it was first recognized as a distinct clinical entity in 1976. The disease is characterized by a progressive, symmetrical descending paralysis of cranial nerves with eventual involvement of axial and trunk muscle innervation. Most infants progress to complete respiratory failure. An initial report in 1979 recommended early tracheotomy for avoidance of long-term intubation complications. However, over the past 10 years at St. Christopher's Hospital for Children, analysis of airway management in 11 patients with infant botulism revealed a median intubation time of 16 days. Following extubation, all patients progressed to complete respiratory recovery without adverse laryngotracheal sequelae. Otolaryngologists consulted for the airway management of infants with botulism should adopt a conservative approach with meticulous monitoring of endotracheal tube sizes and leak pressures. Tracheotomy is rarely required. PMID- 1405987 TI - Vincristine-induced recurrent laryngeal nerve paralysis. AB - Vincristine-sulfate-related vocal cord paralysis has been reported infrequently in the literature. The neurotoxicity of the vinca alkaloids is well-known; however, the potential for cranial nerve involvement is not widely recognized. Given the complexity of the typical patient receiving such a chemotherapeutic agent, the potential for misdiagnosis is high. Many patients have primary tumors or metastatic lesions in sites that could cause the clinician to overlook this reversible cause of neurologic dysfunction. This study describes the first three reported pediatric cases of vincristine-induced vocal cord paralysis. Two patients developed increasing stridor secondary to bilateral vocal cord paralysis; the third developed a unilateral vocal cord paralysis. All resolved spontaneously upon withdrawal of the vincristine. Vinca-alkaloid-induced vocal cord paralysis is a potentially dangerous but reversible lesion. Otolaryngologists should be aware of the association between these agents and cranial nerve neuropathies. PMID- 1405988 TI - The electrophysiologic and histologic effects of the Argon Beam Coagulator on peripheral nerves. AB - The electrophysiologic and histologic effects of the Bard Argon Beam Coagulator (ABC) were investigated in the New Zealand White rabbit. Thirty-four rabbits were divided into three groups. Controls underwent simple femoral exploration and closure. The remaining rabbits' femoral nerves were spot coagulated with either the ABC or standard electrosurgical unit (ESU). Stimulus thresholds were recorded before treatment and again prior to sacrifice at 0, 30, 60, or 120 days. Thresholds were significantly elevated for the ABC and ESU compared to controls (P = .0077 and .0351, respectively). Changes in threshold were greater for the ABC than for the ESU, but were not significant. All ABC- and ESU-treated nerves had significant histologic injury when compared to controls (P < .0002). Although the ABC may be clinically safe, significant injury to rabbit femoral nerves occurs when they are exposed to energy emitted by this instrument. PMID- 1405989 TI - Anatomic correlates of normal and diseased adenoids in children. AB - In order to better understand the pathogenesis and sequelae of obstructive adenoid hyperplasia in children, the anatomic relationships of the adenoids to the hard and soft palates, oropharynx, and nasopharynx were studied in vivo in 94 children. Direct, intraoperative palatal, nasopharyngeal, and oropharyngeal measurements were performed in 19 children with normal, nondiseased adenoids (controls [C]) and compared to 75 children undergoing adenoidectomy for obstructive adenoid hyperplasia (OAH) (n = 44) or chronic adenoid infection (CAI) (n = 31). As expected, the weight and volume of the adenoids removed were significantly greater in the OAH vs. CAI group (P < .001). Before adenoidectomy, the volume of the nasopharynx was significantly smaller in the OAH group; however, nasopharyngeal volumes after adenoidectomy were quite similar in all three groups and ranged from 5.4 to 6.2 cc. Only the change in the volume of the nasopharynx after adenoidectomy for obstruction was significant (2.5 +/- 1.2 cc, P < .01). Differences in oropharyngeal and palatal dimensions were not associated with longstanding obstruction from adenoid hyperplasia. These data indicate that the nasal obstruction from adenoid hyperplasia is due to an absolute increase in adenoid size rather than a relatively smaller nasopharynx. Differences in palatal and oropharyngeal dimensions usually described and attributed to longstanding nasal obstruction could not be demonstrated in this study. PMID- 1405990 TI - Continuous pressure measurements in the pharynx and esophagus during sleep in patients with obstructive sleep apnea syndrome. AB - Pressure measurements were made preoperatively at six sites in the pharynx and esophagus in 18 obstructive sleep apnea syndrome (OSAS) patients, 3 social snorers, and 6 healthy normal controls. Repeat measurements were made approximately 2 months after uvulopalatopharyngoglossoplasty (UPPGP) in 10 of the OSAS patients. The pressure transducers were contained in a thin silicone tube inserted through one nostril, and measurements were made both in the awake state and throughout a night's sleep. Oxygen saturation was also continuously recorded and, additionally, nasal and oral airflow measurements were made as the postoperative control. The majority of patients had obstruction in more than one pharyngeal segment, and the site(s) of obstruction differed in the awake and sleeping states. After UPPGP, 3 of the patients had neither subjective nor objective evidence of obstruction, while the remaining 7, although subjectively improved, had varying degrees of residual obstruction in the nasopharynx and at the level of the soft palate. PMID- 1405991 TI - Relationship of chronic ethmoidal sinusitis, maxillary sinusitis, and ostial permeability controlled by sinusomanometry: statistical study. AB - Three hundred sixty-seven successive patients suffering from chronic maxillary sinusitis (CMS) were thoroughly examined by means of maxillary sinusoscopy, a CT scan of the facial sinuses, and sinusomanometry (SMM). Ninety-eight cases of unilateral CMS, 269 cases of bilateral CMS, and 444 chronic ethmoidal sinusitis (CES) cases were evaluated. According to SMM, the maxillary ostia were divided into two groups: 1. maxillary ostium patency (MOP) group and 2. the maxillary ostium nonpatency (MONP) group. The unilateral and bilateral pathologies were separately analyzed so as to minimize the effects of general or systemic causes on the results. MONP is, in both bilateral and unilateral groups, significantly linked with the presence of ethmoidal sinusitis (P < 10(-6); P = .026), while the correlation between MOP and the ethmoid status does not appear to be significant in either group. Thus, there seems to be a close relationship between CES and maxillary ostial dyspermeability in cases of CMS. PMID- 1405992 TI - The microsurgical anatomy of the abducens nerve in its intracranial course. AB - The microsurgical anatomy of the abducens nerve through its intracranial course was studied in 20 specimens obtained from 10 cadaver heads fixed in formalin. Another 20 specimens were used to study the pattern of branching of the nerve trunk. The following intracranial segments were studied: subarachnoid or intracisternal, petroclival, and intracavernous. Angulations, neurovascular relationships, and branching patterns of the nerve are described. The long intracranial course of the abducens nerve, its tortuosity, and its tight attachment to the skull base at the level of the petrous apex may influence its vulnerability in some pathological conditions. PMID- 1405993 TI - Electrically evoked auditory brainstem response monitoring of auditory brainstem implant integrity during facial nerve tumor surgery. AB - Evoked potentials identified as electrically evoked auditory brainstem responses (EABRs) have been recorded from a patient in response to electrical stimulation of the cochlear nucleus via an auditory brainstem implant. Recording such EABRs during surgery for removal of an ipsilateral facial nerve tumor provided a means to monitor the integrity of the implant. The presence of stable EABRs similar to those obtained before surgery indicated that the lead wires had not been severed and that the implanted electrodes had not been dislodged. EABR recording may also be useful for assisting with positioning the stimulating electrodes during initial implantation surgery, by verifying that stimulation can activate the auditory system. PMID- 1405994 TI - Ventricular dysphonia: a profile of 40 cases. AB - Ventricular dysphonia is a poorly understood disorder involving ventricular fold participation during phonation. A population of ventricular dysphonia patients was evaluated using phonatory function studies such as laryngovideostroboscopy, advanced acoustic analysis, and electroglottography to identify shared epidemiologic characteristics and to discuss possible neuromuscular mechanisms and causes. Forty patients with ventricular dysphonia were studied and epidemiologic, acoustic, and histologic data were analyzed. In almost all cases, the authors found abnormalities affecting the glottis caused by a related medical condition. The abnormalities included true vocal cord (TVC) aperiodicity in 100% of the patients, TVC asymmetry in 65%, a laryngeal mass or foreign body (usually Teflon) in 35%, TVC erythema or edema in 32.5%, and TVC bowing in 22.5%. Ventricular dysphonia seems to be primarily a compensatory mechanism for glottic dysfunction. Therapy is based on identifying and correcting the underlying abnormalities. Laryngovideostroboscopy is a particularly important tool in examining chronic dysphonia. PMID- 1405995 TI - Balance rehabilitation therapy. PMID- 1405996 TI - Measurement of cochlear blood flow in sudden deafness. PMID- 1405997 TI - Laser etching of teeth for orthodontic bracket placement: a preliminary clinical study. AB - Current interest in the use of layers in clinical dentistry has suggested that this technique may be applicable to enamel etching in orthodontics. A pulsed Nd:YAG laser was used to etch the enamel surfaces of teeth in vivo prior to the bonding of orthodontic brackets with composite resin. Overall laser bonding took considerably longer, was less reliable in terms of bond strength, and produced more discomfort than conventional acid etching. The use of the ND:YAG laser for etching teeth prior to bonding orthodontic brackets is not recommended. PMID- 1405998 TI - Effect of the ArF excimer laser on human enamel. AB - Human enamel surface was irradiated with ArF excimer laser and examined under light microscopy and scanning electron microscopy (SEM). Enamel surface was irradiated at three different areas with different energy fluences. It is demonstrated that the ArF excimer laser causes ablation of the calcified hard enamel tissue. Ablation curves were measured. There was no significant difference found in the etch depth between the three different areas of enamel surface. The morphology of the irradiated areas seen under the SEM was found to be dependent on energy fluence. It changed with increase in energy fluence from being etched to forming a smooth, fused, glaze-like surface and then at very high energy fluences producing a rough surface. The influence of the laser irradiation was confined to the irradiated area only, with no visible heat damage to the surroundings. These results suggest that excimer laser could be applied in a controlled and defined manner for tooth enamel treatments in dentistry. PMID- 1405999 TI - Endoscopic laser therapy of the watermelon stomach. AB - Endoscopic laser therapy has been used in the treatment of vascular lesions throughout the gastrointestinal tract. The "watermelon stomach" is a pattern of vascular ectasia in the gastric antrum that results in chronic gastrointestinal blood loss and iron deficiency anemia. We have treated 7 transfusion dependent patients with a watermelon stomach using endoscopic laser therapy. Four of these patients were treated with the argon laser and 3 with the Nd:YAG laser. Patient age and prior transfusion requirements were similar in both groups. The mean number of treatments to obliterate vascular lesions and eliminate the need for transfusions was 5.75 +/- 0.89 (SEM) for the argon laser and 2.33 +/- 0.27 for the Nd:YAG laser (P < 0.05). Lesions recurred and required retreatment in 1 patient treated with the Nd:YAG laser and 3 patients treated with the argon laser (mean follow-up of 35 months). We conclude that endoscopic laser therapy with either the argon or Nd:YAG laser is an effective treatment modality for antral vascular ectasia (watermelon stomach). The Nd:YAG laser requires fewer treatment sessions than the argon laser to obliterate the lesions without increased risk of complications. PMID- 1406000 TI - Treatment of distal ureteral tumors using endoscopic argon photoirradiation. AB - This is the first report on the use of endoscopic argon photoirradiation to treat patients with low-grade ureteral tumors involving the distal ureter. Using a rigid ureteropyeloscope, a 300 mu or 600 mu quartz fiber, and 5 watts (W) of power in a continuous-wave mode, the lesions were ablated without complication. Patients remain free of ureteral recurrence after 5, 7, and 22 months. We conclude that the shallow (1 mm) depth of penetration and the ability to use the fiber in either a contact or noncontact mode provide the surgeon a large margin of safety and low risk of ureteral perforation. PMID- 1406001 TI - Effect of aspirin on photodynamic therapy utilizing chloroaluminum sulfonated phthalocyanine (CASP). AB - The efficacy of photodynamic therapy (PDT) is mediated through a direct vascular effect. Interference with platelet function and resulting vascular stasis have been recently demonstrated utilizing the photosensitizer dihematoporphyrin ether (DHE). We examined the effect of aspirin, a known inhibitor of both cyclooxygenase and platelet activity, on PDT using chloroaluminum sulfonated phthalocyanine (CASP). Thirty-six rats implanted with a window chamber were given either 0.1 mg/kg (low dose) or 10 mg/kg (high dose) aspirin immediately before, immediately after, or 6 hours after the completion of CASP-PDT. Aspirin in either dosage did not appear to have any effect on the window vasculature when given immediately after light exposure. A moderate inhibition of vascular response was seen in animals treated with aspirin pre-PDT, whereas high-dose aspirin completely abrogated the CASP-PDT vascular response when given 6 hours post-PDT. These data indicate that aspirin can effect CASP-PDT in both time-dependent and dose-dependent fashions. PMID- 1406002 TI - Changes in type I collagen following laser welding. AB - Selection of ideal laser parameters for tissue welding is inhibited by poor understanding of the mechanism. We investigated structural changes in collagen molecules extracted from rat tail tendon (> 90% type I collagen) after tissue welding using an 808 nm diode laser and indocyanine green dye applied to the weld site. Mobility patterns on SDS-PAGE were identical in the lasered and untreated tendon extracts with urea or acetic acid. Pepsin incubation after acetic acid extraction revealed a reduction of collagen alpha and beta bands in lasered compared with untreated specimens. Circular dichroism studies of rat tail tendon showed absence of helical structure in collagen from lasered tendon. No evidence for covalent bonding was present in laser-treated tissues. Collagen molecules are denatured by the laser wavelength and parameters used in this study. No significant amount of helical structure is regenerated on cooling. We conclude that non-covalent interactions between denatured collagen molecules may be responsible for the creation of tissue welding. PMID- 1406003 TI - Preliminary evaluation of a new high power diode laser. AB - A high-powered semiconductor diode laser (805 nm) has recently been developed for medical use. The laser-tissue interactions of this wavelength have been compared with Nd:YAG (1064 nm). When used in the contact mode, the extent of tissue vaporization and zones of thermal necrosis produced by these two lasers were similar. The diode laser was also an effective and haemostatic laser scalpel. This compact laser unit has potential advantages over existing Nd:YAG lasers. PMID- 1406004 TI - Optical properties of Intralipid: a phantom medium for light propagation studies. AB - Intralipid is an intravenous nutrient consisting of an emulsion of phospholipid micelles and water. Because Intralipid is turbid and has no strong absorption bands in the visible region of the electromagnetic spectrum, and is readily available and relatively inexpensive, it is often used as a tissue simulating phantom medium in light dosimetry experiments. In order to assist investigators requiring a controllable medium that over a finite range of wavelengths is optically equivalent to tissue, we have compiled previously published values of the optical interaction coefficients of Intralipid, most of which were measured at a wavelength of 633 nm. We have extended the measurements of the absorption and reduced scattering coefficients from 460 to 690 nm and the total attenuation coefficient from 500 to 890 nm. These measurements show that, for stock 10% Intralipid, the absorption coefficient varies from 0.015 to 0.001 cm-1 between 460 and 690 nm, the reduced scattering coefficient varies from 92 to 50 cm-1 between 460 and 690 nm, the total attenuation coefficient varies from 575 to 150 cm-1 between 500 and 890 nm, and the average cosine of scatter varies from 0.87 to 0.82 between 460 and 690 nm. With these data, we discuss the design of an optically tissue-equivalent phantom consisting of Intralipid and black India ink. PMID- 1406005 TI - Ultrafast imaging of tissue ablation by a XeCl excimer laser in saline. AB - To determine the temporal evolution of laser induced tissue ablation, arterial wall specimens with either hard calcified or fatty plaques and normal tissue were irradiated in a 0.9% saline solution using a XeCl excimer laser (wavelength 308 nm, energy fluence 7 J/cm2, pulse width 30 ns) through a 600 microns fused silica fiber pointing perpendicular either at a 0.5 mm distance or in direct contact to the vascular surface. Radiation of a pulsed dye laser (wavelength 580 nm) was used to illuminate the tissue surface. The ablation process and the arising bubble above the tissue surface were recorded with a CCD camera attached to a computer based image-processing system. Spherical cavitation bubbles and small tissue particles emerging from the irradiated area have been recorded. The volume of this bubble increased faster for calcified plaques than for normal tissue. PMID- 1406006 TI - Power density and exposure time of He-Ne laser irradiation are more important than total energy dose in photo-biomodulation of human fibroblasts in vitro. AB - The absorption spectrum of human fibroblast monolayers showed several absorption peaks, among them one at a wave-length of 630 nm. Cultures of these fibroblasts were subjected to He-Ne laser (632.8 nm) irradiation of various energy doses by varying power density and exposure time. On three consecutive days the cell monolayers were irradiated for periods between 0.5 and 10 min. Laser power varied from 0.55 to 5.98 mW. Both cell number and collagen type I production were determined for each irradiation condition within one experiment. Results show that laser power below 2.91 mW could enhance cell proliferation (as determined by cell counting), whereas higher laser power (5.98 mW) had no effect. Stimulatory effects were most pronounced at irradiation times between 0.5 and 2 min. Collagen type I production (as determined by an ELISA) was affected in the opposite direction to cell proliferation: when the cell proliferation was increased, collagen type I production was decreased. From these experiments it is clear that exposure time and power density determine the effects of laser irradiation. Both stimulation and inhibition of the observed cell properties can be obtained with the same laser on the same cells. PMID- 1406007 TI - Pulsed dye laser treatment of benign cutaneous pigmented lesions. AB - Superficial benign cutaneous pigmented lesions that commonly present to the dermatologists and plastic surgeons have been treated by many conventional modalities such as dermabrasion, depigmenting creams as well as several types of lasers. Many of these treatment modalities lack specificity of injury, which has meant that normally pigmented and even non-pigment containing structures such as collagen as well as the hyperpigmented lesion itself have all been indiscriminately destroyed. This has resulted variously in hypopigmentation, hyperpigmentation, in addition to scar formation in some cases. A coaxial 504 nm laser with a pulse duration of 300 nsec was used to treat fifty two patients with superficial benign cutaneous pigmented lesions. Although the number of treatments required to clear the lesion varied according to the type of lesions being treated, on average, between 2 and 4 treatments were required to completely eradicate the superficial benign cutaneous pigmented lesions using 504 nm pulsed dye laser. The skin at the site successfully cleared of the pigmented lesion remained normal in skin color, texture, markings, and mobility. PMID- 1406008 TI - EMLA for laser treatment of portwine stains in children. AB - Vascular-specific lasers with pulse durations of between 300 and 500 microseconds are the treatment of choice for portwine stains (PWS), particularly in children. Although the discomfort felt following laser irradiation from a single pulse is transient, these sensations are intensified when multiple pulses are delivered over a confined area of skin. Because 75-80% of PWS are located in the head and neck regions, laser treatment of these sites tends to be more painful than those located in most other parts of the body. A prospective double blind randomized study, assessing pain during laser irradiation on PWS skin occluded with either EMLA, placebo, or no cream (control) was performed in 73 PWS subjects between 5 and 16 years of age. Analysis of the data showed that the pain scores for EMLA treated sites were the smallest, the control scores tended to be the highest, with the placebo scores in the middle. The differences between the treatments were significant (P < 0.0001). PMID- 1406009 TI - Treatment of lupus pernio with the flashlamp pulsed dye laser. AB - Lupus pernio, a form of cutaneous sarcoidosis usually affecting the face, is often disfiguring and resistant to therapies, both medical and surgical. To our knowledge, there have been no previous reports of laser therapy for this condition. We describe a case of nasal lupus pernio successfully managed with the flashlamp pulsed dye laser. PMID- 1406010 TI - Laser Raman spectrum of calcified human aorta. PMID- 1406011 TI - [Proton pump blockade and Helicobacter pylori: status of current knowledge and clinical importance]. PMID- 1406012 TI - [Antibiotic prevention and therapy of infectious complications in ERCP]. AB - Endoscopic retrograde cholangiopancreatography (ERCP) may be complicated by bacteremia, cholangitis, or biliary sepsis. Bacteremia during ERCP implies a potential risk of endocarditis in patients with valvular prostheses or a previous history of infectious endocarditis. For these patients antibiotic prophylaxis prior to ERCP is recommended. Cholangitis or biliary sepsis may develop after ERCP in patients with obstructed bile ducts. In these patients antibiotics should be administered until adequate drainage of biliary obstructions is achieved. Antibiotic prophylaxis and antibiotic therapy must consider the spectrum of micro organisms which is normally found in each of these situations. Regarding bacteremias associated with ERCP gram-positive cocci predominate, whereas cholangitis and biliary sepsis are caused mainly by gram-negative rods like Escherichia coli, Pseudomonas aeruginosa, or Klebsiella spp. PMID- 1406013 TI - [Endoscopic sonography in esophageal cancer]. AB - Esophageal carcinomas are visualized endosonographically as localized thickenings of the gullet wall with disruption of its echo-layers. The pT-stage is correctly assessed by endosonography in 84% (73-92%). In up to 20% overstaging in the early phases may be caused by accompanying inflammation. The sensitivity for diagnosing local lymph node metastases is 80% (69-90%). The method is well suited for monitoring the course during radio-chemotherapy and for detection of a relapse after operation. At the present time endosonography is the most efficient method in the locoregional staging of esophageal carcinomas. Especially in early tumor stages pT1 and pT2 it is clearly superior to computed tomography. In advanced stages (pT4) in up to 40% of cases marked tumor stenosis, that cannot be passed with the ultrasonic probe, prevents endosonographic staging. However, despite its excellent detail resolution the etiology of a circumscribed wall thickening cannot be determined with absolute accuracy by intraluminal sonography. Based on the echo-pattern inflammatory alterations and scar tissue cannot be definitely distinguished from malignant tumors. PMID- 1406014 TI - [Acute liver failure in metastatic melanoma]. AB - Only seven cases of occult malignancy clinically presenting as acute liver failure due to liver metastases have been outlined in literature so far. In six cases the primary tumor originated histomorphologically from pancreas, bronchus or mamma, in one case the patient died before histological diagnosis. This case report describes the only ten days lasting anamnesis of a 42-year-old man, who felt completely healthy before. Only the autopsy and the immunohistological staining of the taken biopsies led to the diagnosis of an amelanotic melanoma. The site of the primary lesion remained unclear. PMID- 1406015 TI - Leprosy control and the implementation of multiple drug therapy: to what extent can the operational strategy be simplified for primary health care? PMID- 1406016 TI - Evaluation of four semi-synthetic Mycobacterium leprae antigens with sera from healthy populations in endemic and non-endemic areas. AB - In order to determine the frequency of occurrence of antibodies to semisynthetic antigens of Mycobacterium leprae in clinically healthy nonpatient populations and to establish a 'baseline' for comparison with antibody frequencies in both patients with a history of leprosy and their contacts, ELISAs were conducted using representative sera from two areas: a leprosy endemic area, Cebu City, Philippines and a nonendemic area for leprosy Chicago, Illinois, USA. These sera were tested, by an indirect IgM ELISA, for the presence of antibodies reacting with four semisynthetic antigens based on the phenolic glycolipid I antigen of M. leprae: ND-O-BSA (natural disaccharide with octyl linkage to bovine serum albumin), NT-O-BSA (natural trisaccharide with octyl linkage to BSA), ND-P-BSA (natural disaccharide with phenolic ring linkage to BSA) and NT-P-BSA (natural trisaccharide with phenolic ring linkage to BSA). Using an OD reading > or = 0.16 as positive, the antigen with the lowest background seroreactivity was ND-O-BSA, which reacted with 5/398 (1.3%) sera from Cebu, and 3/426 (0.7%) sera from Chicago. A total of 10 (2.5%) of 398 sera from the endemic area reacted with at least one antigen and 5 (1.3%) sera reacted with all four semisynthetic antigens. Of the 426 sera from Chicago, 12 (2.8%) were reactive with at least one antigen and 3 (0.7%) were reactive with all four semisynthetic antigens. Mean ELISA values for the 22 positive sera for each antigen ranged from 0.17 to 0.3 OD units, while the mean values for all sera in each area ranged from 0.01 to 0.04 OD units for all four antigens. Reactivity of 14 of the positive sera to some antigens, but not all four semisynthetic antigens, indicated that the carrier and linker arms might be associated with this background reactivity. Investigation of alternative linker arms and carriers is warranted. We conclude that nonspecific background reactivity to the semisynthetic antigens representing the PG-I molecule of M. leprae is 0.7-1.3%, based on a > or = 0.16 OD cutoff value. From these data it was concluded that reactivity in individuals free of leprosy was low enough to warrant use of these antigens in a diagnostic setting, such as screening household contacts and highly endemic populations. When incidence and prevalence of leprosy are low, testing with these antigens would not be cost effective, unless applied to high risk individuals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1406017 TI - Leprosy in French Polynesia. Epidemiological trends between 1946 and 1987. AB - The analysis of computerized data (OMSLEP system) on patients from French Polynesia followed since 1940 has shown a decrease in the mean annual detection rates for leprosy, all forms combined, from 24.73 per 100,000 inhabitants in 1946 to 8.1 per 100,000 in 1987 (y = -0.49 x + 45.83; p < 0.05). In fact, the decrease was significant (y = -1.18 x + 83.54; p < 0.05) during the first half of the study period (1946-66), but not during the second half (1967-87). Similarly, a significant decrease in all of the specific mean annual detection rates (according to the form of leprosy and to the sex and age of patients), in the proportion of multibacillary patients among the total of newly detected cases, and in the proportion of all patients with disabilities at the onset of leprosy was observed only during the first half of the study period (1946-66). Nevertheless, when comparing age-specific cumulative detection rates, calculated by 10-year age groups over the period 1946-66, to those of the period 1967-87, an ageing of the leprosy population was noted. Finally, the decrease of mean annual detection rates was greater in the smaller populations of remote islands than in the population of Tahiti, the main island, where 70% of the total population were living during the study period. This decline was shown to correspond to an effective improvement of the leprosy situation which could be attributed, among other factors (such as economic development and systematic BCG vaccination), to the implementation of a control programme for leprosy in 1950. The introduction in 1982 of multidrug therapy for all patients suffering active leprosy has raised the hope of a subsequent decline of leprosy in French Polynesia in the near future. PMID- 1406018 TI - Leprosy in French Polynesia. The possible impact of multidrug therapy on epidemiological trends. AB - In 1982, following the recommendations of a WHO study group, multidrug therapy (MDT) was introduced into French Polynesia to treat all patients suffering from active leprosy, and--only on request--those still on dapsone monotherapy. After 5 years, a clear-cut decrease of prevalence and mean annual detection rates for leprosy (except for detection rates among children aged less than 15 years, many of such cases being detected early by increased household contact training) has been observed. There was also a decrease in the proportion of newly detected cases with disabilities. During the 21-year period preceding the introduction of MDT into the control programme, mean annual detection rates for leprosy had remained stable, and this led to the consideration that such a decrease was due neither to the natural decline of the disease nor to the economic improvement of the country. Our results, together with the fact that, to date, the relapse rate was nil in the Polynesian patients put on MDT, strongly suggest that the implementation of MDT has resulted in a decrease of detection rates for leprosy which may be a consequence of a decrease in the transmission of the disease. PMID- 1406019 TI - Leprosy control in 7 districts of south Sulawesi, Indonesia, 1986-91. AB - This paper describes the leprosy control programme in 7 districts of the South Sulawesi Province in Indonesia. This province is reported to have the highest prevalence of leprosy in the country. The programme started in 1986 with re registration of all patients on the cumulative registers. Strict criteria for admission of patients to MDT were initially applied. In 1990 it appeared that these criteria had been too strict, thus necessitating a second re-registration of patients still on DDS monotherapy. More flexible criteria for admission to MDT led to an increase in MDT coverage from 45% to 78% within 6 months. By April 1991, 5 years after the start of the programme, the registered prevalence had decreased from 4.4 per 1000 in 1986 to 1.6 per 1000; the coverage with MDT had increased from 6% in 1986 to 78%, and the case detection rate remained stable around 4 per 10,000 after an initial increase at the start of the programme. PMID- 1406020 TI - Results of surgical procedures for the correction of foot-drop and of lagophthalmus due to leprosy. AB - Leprosy mutilations of the muscles and skeleton can be relieved by reconstructive surgery, but evaluation of the results of these operations is seldom undertaken. Between 1975 and 1984, 59 leprosy patients were operated on at the Marie Adelaide Leprosy Centre, Karachi, Pakistan, for lagophthalmus with the transposition of the posterior tibial muscle. We were able to re-examine 39 patients: tibialis posterior transposition was performed 25 times, and temporalis transposition was carried out 33 times; 18 of the 25 patients with the tibialis posterior transposition were pleased with the result, 7 were not: 21 patients could extend their feet above the neutral position; 24 of the patients with the temporalis transposition were satisfied, 9 were not: complete closure was demonstrated in 21 eyes; Persistent corneal damage was noted in 15 eyes; 12 of the 23 male patients cared for themselves, 16 lived with their families; 7 of the 8 female patients lived with their families. The results of the rehabilitation, in relation to the degree of mutilation, are considered satisfactory for a developing country. These surgical procedures give a good result, provided they are followed by intensive physiotherapy. PMID- 1406021 TI - Neuritic leprosy: epidemiology and therapeutic responsiveness. AB - We studied epidemiology, progression and therapeutic responsiveness in 62 cases of neuritic leprosy. Numbness was the main presenting symptom. Mononeuritis involving the ulnar nerve, followed by the common peroneal nerve was the commonest presentation. The lepromin test was positive in 34 cases while a slit skin smear was negative in all cases. We treated 20 of these cases with dapsone monotherapy and 5 cases (25%) developed a skin lesion after an average duration of 3 months' treatment. We treated 42 cases with a combination of dapsone and rifampicin, and 3 cases (7%) developed a skin lesion after an average duration of 2-6 months. The subsequent diagnosis in cases developing skin lesions was borderline--lepromatous in 1 case, borderline-tuberculoid in 4 cases, tuberculoid in 2 cases and indeterminate in 1 case. PMID- 1406022 TI - Neurological examination of patients suffering from leprosy: is it worthwhile? AB - We examined 28 male leprosy patients to discover if a more extensive neurological investigation than usual would be worthwhile in diagnosis and/or management. Our findings were fully compatible with what might be expected from a mononeuritis multiplex, either due to leprosy or other causes. The following observations are noteworthy. Changes of position sense and a decrease of some tendon reflexes were present in a minority of the patients. In soles of the feet, considered to be an- or hypaesthetic, some residual pain sensation could occasionally be detected. Functional testing of at least one muscle group (m. triceps surae) appeared to be more reliable than manual testing according to MRC criteria. We concluded that an extensive neurological examination is probably not required for diagnosis. It does provide, however, more accurate information on the extent of damage to the peripheral nervous system, which may be important for management and for assessment of treatment effects. The use of a myometer is advocated. PMID- 1406023 TI - Primary neuritic leprosy in a black South African. AB - A case of primary neuritic leprosy in a black South African is described, in which the multiple peripheral nerves were affected. The clinical picture and electrophysiological studies are in keeping with a picture of mononeuritis multiplex. Selective involvement of the facial nerve branches with normal blink reflex latencies was observed. The biopsy of the sural nerve disclosed features most consistent with borderline leprosy. PMID- 1406024 TI - Estimated number of leprosy cases in the world. AB - Planning for leprosy control requires estimates of the number of leprosy patients at different levels. During the period between the mid-1960s and the mid-1980s, global estimates had remained constant at between 10 and 12 million. The introduction of multidrug therapy (MDT) in many countries and the consequent reduction of the disease's prevalence has necessitated a reassessment of this. Based on available information and its interpretation, the number of leprosy cases in the world for 1991 has been estimated at 5.5 million. The number of individuals deformed by leprosy, including those cured of the disease, has been estimated at between 2 and 3 million. PMID- 1406025 TI - Modified multiple drug therapy in the National Leprosy Eradication Programme, India. PMID- 1406026 TI - Minocycline cures tuberculoid leprosy. PMID- 1406027 TI - The teaching of leprosy in the medical colleges of Orissa, India. PMID- 1406028 TI - The role of health systems research in leprosy control. PMID- 1406029 TI - Issues involved in the rapid assessment of the leprosy problem. AB - Sample surveys for estimation can prove very expensive and time-consuming because of the enormous sample sizes usually required. Where sample surveys have to be undertaken, diagnoses should be limited to detecting a case of leprosy, without attempting skin smears etc. in order to classify by types. Usually enough knowledge is available on the approximate proportion of multibacillary (MB) cases in most communities, and this knowledge could be utilized for estimating the caseload by types of leprosy. Again intensive tracing of nonrespondents could be limited to either males or females depending on convenience, and well-known sex ratios among patients utilized for deriving estimates for the other sex. The type of rapid methods of estimation depend on three types of situations: (1) before multidrug therapy (MDT); (2) 5 years or more after MDT; and (3) less than 5 years after MDT. In the first situation one or more of the following methods are suggested: (i) extrapolation from registered cases; (ii) extrapolation from child prevalence; and (iii) conducting rapid village surveys. In situations where MDT has been introduced for 5 years or more the registered cases plus a small number, depending on local experience, would seem to be adequate. When MDT was introduced less than 5 years before, it is suggested that the prevalence rates be obtained by statistical interpolation drawing on the experience from areas which have had more than 5 years of MDT. PMID- 1406030 TI - Report on the group discussions on the needs and prospects for epidemiological tools in leprosy control. PMID- 1406031 TI - Summary of 'Estimation of the leprosy problem through health services data'. PMID- 1406033 TI - Needs and prospects for epidemiological tools in leprosy control. PMID- 1406032 TI - The epidemiology of disability in leprosy including risk factors. PMID- 1406034 TI - Epidemiometric modelling in leprosy based on Indian data. PMID- 1406035 TI - Epidemiological modelling for tropical disease control. PMID- 1406036 TI - Towards the use of decision sciences in leprosy control. PMID- 1406037 TI - Major issues involved in the evaluation of leprosy control programmes through MDT. PMID- 1406038 TI - Defining a case of leprosy. AB - The biological and technical hurdles confronting the development of new diagnostic tools are manifestly great in leprosy. Leprosy diagnosis in the field, for control as well as for research purposes, will have to remain, for the time being, predominantly clinical. It is important that the significance and relevance of diagnosing so-called 'early' lesions must be viewed in the context of the objectives of leprosy control. All evidence suggests that the majority of these 'cases' are not likely to progress in the individual, nor is there any evidence that these 'cases' are of any importance for the transmission of the disease. At its best, such 'cases' may be a sign of temporary infection which will disappear spontaneously within a few months without leaving any residual signs. It is more likely that the majority of these are not cases of leprosy. In making such a diagnosis its ethical implications on the individual, his family and the local society must be considered, given the intense social stigma this diagnosis will generate; besides the cost of treatment and the potential risk of serious side-effects due to treatment. It may be justifiable to have a broad definition if the incidence of leprosy is still high and all reported cases are to be accepted as valid. But once the backlog of cases has been detected and, as a result of control efforts, the number of new cases begins to decrease, there is a need to narrow the case definition for national statistics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406039 TI - Surveillance and monitoring of multidrug therapy using cohort analysis. PMID- 1406040 TI - Indicators for use in leprosy control programmes. PMID- 1406041 TI - OMSLEP as an evaluation tool. PMID- 1406042 TI - The measurement of the epidemiological impact of multidrug therapy. PMID- 1406043 TI - Treatment failures with multidrug therapy. PMID- 1406044 TI - The relevance of future leprosy vaccines to disease control. PMID- 1406045 TI - Interleukin 6 modulation of second messenger systems in anterior pituitary cells. AB - We investigated the effect of interleukin-6 (IL-6) on second messenger systems in anterior pituitary (AP) cells. The acute exposition of membranes derived from the pituitary gland to IL-6 did not modify basal and forskolin-stimulated adenylate cyclase (AC) activity, as well as inositol phosphate (IP) production and free [Ca(++)]i. Preincubation of AP cells with IL-6 for 20 min did not affect basal second messengers levels, while completely abolished the stimulation by VIP of AC activity, partially inhibited forskolin-stimulated cAMP formation and reduced TRH stimulated IP production. Finally, the pretreatment of AP cells for 20 min with IL-6 also reduced the TRH-induced rise in free [Ca(++)]i. PMID- 1406046 TI - Murine survival of lethal irradiation with the use of human umbilical cord blood. AB - We have found that human umbilical cord blood (HUCB) will routinely protect mice exposed to lethal levels of irradiation. At the end of 50 days, over seventy percent (70%) of mice injected with HUCB survived 900 cGy or irradiation, which produced 100% deaths in the uninjected control animals. Moreover, there was some evidence that human colony stimulating factors further improved survival. Anti Natural Killer cell (NK) antibody was utilized along with HUCB in these studies, however, Anti-NK cell serum alone had no radioprotective effect in mice. The studies reported here suggest the possibility of utilizing HUCB for immediate protection of humans from lethal irradiation. PMID- 1406047 TI - Bioactivation of the hepatocarcinogen N-hydroxy-2-acetylaminofluorene by sulfation in the rat liver changes during the cell cycle. AB - Sulfation activity towards N-hydroxy-2-acetylaminofluorene and 4-nitrophenol was determined in male rat liver cytosol at several time points after partial hepatectomy corresponding to G1-, S-, and M-phase. N-hydroxy-2 acetylaminofluorene sulfation activity decreased by 80% when hepatocytes entered the G1-phase. This lower activity was maintained during the S-phase and M-phase, but was restored when hepatocytes entered the G0-phase again. Sulfation activity towards 4-nitrophenol did not alter after hepatectomy. Various other cytosolic enzyme activities were determined after hepatectomy to investigate the specificity of the decrease in sulfation activity. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were increased in the S- and M-phase by maximally 80% and 60%, respectively. Glutathione-S-transferase and glutamate pyruvate transaminase activity did not alter during the cell cycle. These results indicate that sulfation of N-hydroxy-2-acetylaminofluorene in hepatocytes may depend on the phase of the cell cycle. The relevance of the finding is discussed in relation to the resistance of proliferating (pre)neoplastic hepatocytes to the toxic and mitoinhibitory effects of N-hydroxy-2-acetylaminofluorene. PMID- 1406048 TI - Hemodynamic effects of centrally administered, norcocaine in the rat. AB - Norcocaine is the N-demethylated metabolite of cocaine. It is present in the CNS and is reported to be pharmacologically active. The present study was designed to evaluate the cardiovascular actions of norcocaine following central administration. Wistar Kyoto (WKY) rats were anesthetized with pentobarbital and instrumented for measurement of blood pressure and renal and hindlimb blood flow (via Doppler flowprobes). A cerebroventricular cannula was placed in the lateral ventricle for drug administration. Cocaine or norcocaine was administered centrally in a dose range of 0.025 to 4.0 mg/kg. Under the above experimental conditions, 4.0 mg/kg of norcocaine decreased blood pressure without a significant change in either hind limb or renal blood flow. Central administration of cocaine also produced a similar depressor response. In conscious, unrestrained rats, cocaine produced a pressor response while norcocaine did not significantly alter blood pressure. The depressor response to both cocaine and norcocaine in the anesthetized animal is speculated to be due to the local anesthetic properties of the drugs. PMID- 1406049 TI - Ovarian atrial natriuretic peptide during the rat estrous cycle. AB - The changes in ovarian levels of immunoreactive atrial natriuretic peptide (irANP) and arginine vasopressin (irAVP) were observed during the estrous cycle of rat. We also demonstrated the synthesis of ovarian ANP. In adult 4-day cycling rats, ovarian level of irANP was found to be the highest on proestrus and was to be the lowest on diestrus. Ovarian irANP level inversely correlated with ovarian level of irAVP. On reverse-phase HPLC, two distinct peaks of ovarian irANP, high and low molecular weight forms, existed in the each stage of the estrous cycle. However, no significant changes in plasma and atrial concentrations of ANP were observed during the cycle. The rat ovary contained mRNA coding for ANP. These data showing the synchronized cyclic change of ovarian irANP and irAVP with the estrous cycle suggest that the ovary locally synthesizes ANP and ovarian ANP may play regulatory roles on the follicular fluid dynamics. PMID- 1406050 TI - The effect of dexamethasone on neuropeptide Y concentrations in specific hypothalamic regions. AB - Neuropeptide Y (NPY) is a major hypothalamic peptide which is implicated in the regulation of energy balance and in the activation of the hypothalamo-pituitary adrenal axis. This study aimed primarily to determine the effects on regional hypothalamic NPY levels, of catabolism and weight loss induced in rats by the synthetic glucocorticoid, dexamethasone, injected daily at a dose of 0.4 mg/kg for 7 days. NPY concentrations were significantly raised in the paraventricular nucleus (PVN) of male Wistar rats (45%, p = 0.009; n = 10) compared with saline injected controls (n = 10). Body weight (p less than 0.001) and food intake (p less than 0.001) were significantly reduced, plasma insulin concentrations were increased (p less than 0.001), but there was no change in glucose concentrations. Chronic dexamethasone treatment did not cause the marked NPY increases in the arcuate nucleus (ARC) and other hypothalamic regions which have been observed in other catabolic states causing weight loss. One possible explanation is the high insulin levels induced by dexamethasone, which may have prevented compensatory hyperphagia by suppressing an increase in hypothalamic NPYergic activity. We also examined the acute effects of a single dexamethasone injection on regional hypothalamic levels, to determine whether the drug had a direct action separate from that due to sustained weight loss. In the acute study, groups of rats (n = 7) were examined at 4 h after a single injection of dexamethasone or saline. NPY concentrations were significantly increased in the lateral hypothalamic area (LHA), (60%, p = 0.008) when compared with saline-injected controls, but there was no change in body weight or glucose or insulin concentrations during the 4h interval. Altered transport or release of NPY in the lateral hypothalamic area may be a result of acute feedback regulation by glucocorticoids on the hypothalamus. PMID- 1406051 TI - Ventricular defibrillating properties of catecholamine uptake inhibitors. AB - Ventricular fibrillation (VF) is a fatal event in humans unless electrical defibrillation is applied within minutes. Recent publications describe spontaneous termination of VF in various animals and even in humans. Certain drugs can transfer a fatal, sustained VF (SVF) into a self-terminating, transient VF (TVF). Based on results obtained in animals of various species and ages, we have suggested that the occurrence of TVF requires a high cardiac catecholamine level at the time of VF. According to our hypothesis, drugs which decrease catecholamine reuptake by the sympathetic nerve terminals will increase the ability of the heart ventricles to defibrillate spontaneously. In the present study, we examined the effects of desipramine, maprotiline, mianserin, iprindole, cocaine and amphetamine on the type of VF in cats exhibiting SVF prior to the treatment. The results show that the ability of these compounds to transfer SVF to TVF is closely related to their potency to inhibit catecholamine reuptake. The establishment of the catecholamine related mechanisms of TVF may lead to the development of a new class of antiarrhythmic-defibrillatory drugs. PMID- 1406052 TI - Alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori--a possible mechanism behind gastric injury. AB - Two standard Helicobacter pylori strains showed significant cytosolic alcohol dehydrogenase activity and produced considerable amounts of acetaldehyde when incubated with an ethanol containing solution in vitro. The alcohol dehydrogenase activity of the Helicobacter pylori strains was almost as high as that found in Klebsiella pneumoniae and far greater than that in Escherichia coli or Campylobacter jejuni. The amount of acetaldehyde produced by cytosol prepared from Helicobacter pylori exceeded that by any of the other bacteria studied. The bacterial production of acetaldehyde--a highly toxic and reactive substance- could be an important factor in the pathogenesis of Helicobacter pylori associated gastric injury and increased risk of gastric cancer. PMID- 1406053 TI - Regulation of arginase production by glucocorticoid in three human gastric cancer cell lines. AB - Gastric cancer tissues have high levels of glucocorticoid receptors (GR) and arginase. To investigate the interrelation of glucocorticoid, GR and arginase, three human gastric cancer cell lines (AZ-521, NUGC-3, KATO-III) were treated with hydrocortisone in the presence or absence of a glucocorticoid antagonist RU38486. GR were found to be present in all three lines, and hydrocortisone significantly increased the production of total arginase in all 3 lines. The induction of arginase production by hydrocortisone was inhibited by RU38486. These findings suggest that the regulation of arginase production by hydrocortisone in gastric cancer cells is mediated through GR. PMID- 1406054 TI - Validation of the antral mucosal/submucosal sleeve preparation: studies of gastrin and acetylcholine release in response to luminal stimulation. AB - In the present study we developed an experimental model for direct assessment of antral endocrine cell and cholinergic neural responses to luminal stimulation. A sleeve of antral mucosal/submucosal tissue was prepared from rat antrum, mounted in perfusion chamber, and perfused in both luminal and submucosal compartments. Morphological and functional integrity of the antral sleeve were confirmed by histological examination and measurement of protein synthesis. Antral gastrin release was assessed in response to luminal stimulation with acid, peptone and distension. Luminal acid (pH3) inhibited basal gastrin release by -70.4% and luminal peptone stimulated gastrin release to 210% above control (p < 0.02). Distention of the antral sleeve by hydrostatic pressure (3-25cm H2O) caused stepwise and significant increase in gastrin release that was reversible. 3H acetylcholine was stimulated significantly by KCl (56mM) to values twice control. In summary, these results establish the integrity and responsiveness of the antral sleeve to pharmacological and luminal stimulation. The antral sleeve may be a useful model in assessing antral function in response to luminal stimulation. PMID- 1406055 TI - Similarities between the akinesia induced by carbachol microinjections into the pontine reticular formation and neuroleptic catalepsy. AB - We reported previously that microinjections of carbachol directly into the pontine reticular formation of rats induced intense akinesia. In the present article we report results of tests for rigidity, righting, bracing and clinging which were conducted with the purpose to characterize behaviorally this type of akinesia. After injections of 5-15 micrograms/0.5 microliter of carbachol into the pontine reticular formation the rats were cataleptic, were not rigid when equilibrium was not challenged, had strong righting reflexes and strong bracing and clinging responses. This type of akinesia is different from the catatonia induced by systemic morphine (20 mg/kg IP), but similar to the catalepsy induced by systemic injections of haloperidol (5 mg/kg IP). It is thus suggested that the cataleptic state produced by topical carbachol in the pons is related to the dopaminergic mechanisms important for the cataleptic effect of the neuroleptic drugs. PMID- 1406056 TI - Nephrectomy and a newly identified binding site for angiotensin II in the rat adrenal cortex. AB - Angiotensin II (Ang II) binding sites in adrenal glands of nephrectomized rats were investigated by in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as ligands. Ang II binding site was increased to 161% in the cortex and decreased to 67% in the medulla 48 h after nephrectomy. In the medulla, the AT2 antagonist (PD123177, 5 microM) inhibited specific binding by 90% whereas the AT1 antagonist (DuP753, 5 microM) inhibited by only 10%. In contrast, in the cortex, neither DuP753 (5 microM) nor PD123177 (5 microM) substantially inhibited the binding. Binding in the presence of either the AT1 or AT2 antagonist was abolished by the simultaneous presence of both antagonists. These results suggest the presence of a new Ang II binding site with unique pharmacological properties and differing from currently known subtypes of Ang II receptors, in the adrenal cortex after nephrectomy. PMID- 1406057 TI - Both cyclooxygenase and lipoxygenase inhibitor partially restore the anorexia by interleukin-1 beta. AB - Since the peripheral prostaglandin synthetizing system may at least partly involved in the anorexia that follows central interleukin-1 beta (IL-1) administration, this study was undertaken to investigate the effect of ibuprofen (ip), selective cyclooxygenase blocker and AA 861, selective lipoxygenase inhibitor, on changes of food and water intake by a single injection of IL-1 (2 micrograms/rat, ip). We demonstrated that food and water intake were suppressed by peripheral administration of IL-1. Throughout the entire observation periods, suppressed food intake was partially restored to control levels by ibuprofen, while water intake completely restored. In addition, no significant differences about water/food intake were observed in the IL-1 + ibuprofen-treated groups, respectively. In the next experiment, IL-1 induced anorexia was also partially restored to the control level following pretreatment with AA 861. These results may suggest that other mechanism including lipoxygenase blocker besides prostaglandin production may be involved in IL-1 induced anorexia. PMID- 1406058 TI - The ANF-C receptor is not linked to adenylyl cyclase inhibition in bovine pulmonary artery endothelial cells. AB - The possible inhibition of adenylyl cyclase activity by atrial peptides selective for the ANF-C receptor was investigated in bovine pulmonary artery endothelial cells. In these cells isoprenaline, guanine nucleotide and forskolin dose dependently increased activity over basal levels. In the presence of rANF(99 126), these dose-dependent increases were not reduced, nor were they affected by the ANF-C receptor selective analogue C-ANF(102-121). Furthermore, the selective analogues rANF(103-123) and des[Cys105,Cys121]rANF104-126 had no effect on basal or stimulated adenylyl cyclase activity. It can be concluded that ANF-C receptors are not linked to inhibition of adenylyl cyclase in these cells. PMID- 1406059 TI - Changes in vitamin A status following prolonged immobilization (simulated weightlessness). AB - A study was conducted to investigate the effects of a simulated weightlessness induced by chronic immobilization on vitamin A status. To simulate the stress condition of weightlessness, rats were suspended for 10 days in a special jacket to which metal chains were attached. Animals received a commercial stock diet. Control rats were pair-fed in reference to the suspended rats. As compared with the control, prolonged immobilization resulted in a decrease in body weight gain and an increase in adrenal weight occurred. In the suspended rats, serum concentrations of retinol and retinol-binding protein (RBP) declined. Hepatic retinyl palmitate content increased, and the hepatic retinol level was decreased. The prolonged immobilization led to significantly reduced retinyl palmitate levels in the testis and lung as well as lowered testicular retinol levels. The results suggest that the stress state induced by prolonged immobilization caused accumulation of hepatic retinyl palmitate, decreasing the serum retinol concentration and retinyl ester content in the extrahepatic tissues. PMID- 1406060 TI - The effect of short-term lipid infusion on liver function and biliary secretion in rats. AB - This study was undertaken to determine the effect of various lipid emulsions on the hepato-biliary system in rats. Rats were randomly divided into six groups and infused continuously for 48 hr with either long-chain triglycerides (LCT), medium chain triglycerides (MCT) or a mixture of MCT and LCT. One group infused with physiological saline solution served as controls. Throughout this period the rats received a fat free diet ad libitum. During the last hour of lipid infusion bile was collected for determination of bile flow and composition. Subsequently, the rats were sacrificed and the morphology and lipid content of the liver determined. Only LCT lipid emulsions induced morphological changes and increased liver cholesterol content. In two rats infused with radiolabeled LCT, no labeled cholesterol was found in the liver, indicating that the excess hepatic cholesterol level may originate from enhanced cholesterol mobilization to the liver. Biliary cholesterol and phospholipid concentrations in LCT-treated rats were also elevated, as was the lithogenic index, whereas the other emulsions had no such effects. None of the emulsions affected the plasma liver function tests or bile flow. We therefore conclude that the lithogenicity of the bile in rats is directly related to the lipid components of the total parenteral nutrition and the type of triglyceride infused. PMID- 1406061 TI - Effect of dietary fish oil on the rate of very low density lipoprotein triacylglycerol formation and on the metabolism of chylomicrons. AB - The mechanism by which omega 3 fatty acids lower plasma triacylglycerol levels was investigated. Rats were fed fish oil, olive oil (10% fat by weight) or a nonpurified diet (4% fat by weight) for 15 days. Lipoprotein lipase was inhibited by intra-arterial administration of Triton WR 1339 to estimate hepatic triacylglycerol output. Rats fed the olive oil diet showed a higher rate of triacylglycerol formation than rats fed the omega 3 fatty acid diet or the low fat diet. All three groups showed identical rates of removal from plasma of intraarterially administered artificial chylomicrons that had simultaneously been labeled with cholesteryl [1-14C]oleate and [9,10(n)-3H]triolein. Liver radioactivity and total fat content were lowest in rats fed the fish oil diet, indicating that omega 3 fatty acids were preferentially metabolized in liver. Chylomicrons obtained from donor rats fed either fish oil containing [14C]cholesterol or olive oil containing [3H]cholesterol were removed at similar rates when infused together intraarterially into recipient animals. A slower formation of plasma very low density lipoprotein triacylglycerols in rats fed fish oil is probably due to a faster rate of oxidation of the fatty acid chains in the liver resulting in decreased plasma triacylglycerol concentrations. PMID- 1406062 TI - Effect of dietary fats on some membrane-bound enzyme activities, membrane lipid composition and fatty acid profiles of rat heart sarcolemma. AB - The effect of various dietary fats on membrane lipid composition, fatty acid profiles and membrane-bound enzyme activities of rat cardiac sarcolemma was assessed. Four groups of male weanling Charles Foster Young rats were fed diets containing 20% of groundnut, coconut, safflower or mustard oil for 16 weeks. Cardiac sarcolemma was prepared from each group and the activities of Na+, K(+) ATPase, 5'-nucleotidase, Ca(2+)-ATPase and acetylcholinesterase were examined. ATPase activities were similar in all groups except the one fed coconut oil, which had the highest activities. Acetylcholinesterase activity was also similar in all the groups, however, it was significantly higher in the group fed mustard oil. No significant changes were observed among the groups in 5'-nucleotidase activity, in the cholesterol-to-phospholipid molar ratio and in sialic acid content. The coconut, safflower and mustard oil diets significantly increased cholesterol and phospholipid contents and the lipid-to-protein ratio of cardiac sarcolemma as compared to feeding the groundnut oil diet. The fatty acid composition of membrane lipids was quite different among the various groups, reflecting the type of dietary fat given. The total unsaturated-to-saturated fatty acid ratio was not different among the various groups; however, the levels of some major fatty acids such as palmitic (16:0), oleic (18:1) and linoleic (18:2) acids were significantly different. Cardiac sarcolemma of the group fed safflower oil had the highest polyunsaturated fatty acid content. The results suggest that dietary fats induce changes not only in the fatty acid composition of the component lipids but also in the activities of sarcolemmal enzymes involved in the regulation of cardiac function. PMID- 1406065 TI - A study of the composition of fish liver and body oil triglycerides. AB - Silver-ion high-performance liquid chromatography (Ag(+)-HPLC) was used to study the range and variations in molecular species of triglycerides from industrial, retail and laboratory extracted fish oils. These were contrasted with a typical plant oil. Selected fish oils were fractionated and the fatty acid distribution of the fractions determined by gas-liquid chromatography. Fish oils gave a characteristic Ag(+)-HPLC profile, typified by sharp, intense peaks at the start of the chromatogram and broad, multiple nongaussian peaks for the late eluting components. Triglycerides ranging from those that were wholly saturated to those containing 16 double bonds were isolated. Cod (Gadus spp.), saithe (Pollachius virens) and monkfish (Squatina squatina) liver oils gave similar triglyceride profiles. Mackerel (Scomber scombrus), capelin (Mallotus villosus) and herring (Clupea harengus) body oils gave characteristic triglyceride profiles which were associated with high concentrations of 20:1 and 22:1 fatty acids. Only small amounts of these particular triglycerides were observed for menhaden (Brevoortia spp.), South African anchovy (Engraulis capensis) and Indian sardine (Sardinella longiceps) oils, all of which contained minor amounts of these acids. The latter oils contained highly unsaturated triglycerides, whereas only traces of these were noted for the former. Chromatography with Ag(+)-HPLC can be used for the rapid screening of fish oils and for selecting those oils rich in polyunsaturated acids that may be suitable for enrichment. Cottonseed oil gave well-defined and discrete peaks. Similar peaks were observed in the chromatogram of Omega combination, a mixture of primrose and fish oils. Thus, fish, plant and a mixture of these oils can be readily distinguished. PMID- 1406063 TI - Effect of prenatal and postnatal exposure to ethanol on rat central nervous system gangliosides and glycosidases. AB - We investigated the effect of maternal alcohol consumption on cell number, gangliosides and ganglioside catabolizing enzymes in the central nervous system (CNS) of the offspring. Virgin female rats of the Charles Foster strain were given 15% (v/v) ethanol in drinking water one month prior to conception and during gestation and lactation. At 21 days postnatal age, the offspring were sacrificed and the brains were separated into cerebrum, cerebellum and brain stem to investigate possible regional variations. Compared to controls, wet weight of cerebrum, cerebellum and brain stem, and of spinal cord was decreased in the pups exposed to alcohol. DNA and protein contents were also found to be lowered in all the CNS regions of the pups exposed to alcohol. Conversely, maternal alcohol consumption was found to increase the concentration and the content of total ganglioside N-acetyl-neuraminic (NANA) in CNS of the pups. In addition, alcohol treatment was found to induce alterations in the proportions of individual ganglioside fractions. Interestingly, these alterations are somewhat different than those observed in the neonatal brain and spinal cord of the pups subjected to prenatal alcohol exposure. The alterations in the proportions of ganglioside fractions were shown to be region-specific. Maternal alcohol consumption resulted in decreased activities of sialidase, beta-galactosidase, beta-glucosidase and beta-hexosaminidase. The results suggest that the alcohol-associated increases in ganglioside concentration may be at least partly due to the decreased activities of ganglioside catabolizing enzymes. PMID- 1406064 TI - Fluorospectroscopic analysis of the fluorescent substances in peroxidized microsomes of rat liver. AB - The fluorescent substances formed in rat liver microsomes in the course of lipid peroxidation were investigated by fluorescence techniques. The fluorescence emitted from peroxidizing microsomes continuously increased as lipid peroxidation progressed, while the steady-state fluorescence anisotropy increased and then reached a plateau. A similar increase was observed in the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in peroxidizing microsomes. The fluorescence from peroxidized microsomes consisted of at least three species having short, middle or long fluorescence lifetimes. The lifetimes and relative amplitudes of fluorescence were unaffected by the extent of lipid peroxidation. Both fluorescence of the chromolipids extracted and the proteins isolated from peroxidized microsomes had the same characteristics in fluorescence lifetimes as the fluorescence from whole peroxidized microsomes. Thus, these lipids and proteins appear to be the major biological substances responsible for the fluorescence emanating from whole peroxidized microsomes. Furthermore, fluorescent substances formed in microsomes seem to increase in quantity rather than change in quality as lipid peroxidation progresses. PMID- 1406066 TI - Lipid composition and mitochondrial respiration in warm- and cold-adapted sea bass. AB - The response to cold of liver and heart membrane lipid composition and mitochondrial respiration in reared sea bass (Dicentrarchus labrax L.) was investigated. Fish acclimation was followed during the natural seasonal cycle from August to March. The data on the fatty acid composition of liver and heart polar lipids and on total lipids of liver mitochondria and microsomes did not indicate any increase in unsaturation in response to cold. The enzyme complexes of the liver and heart mitochondrial respiratory chain showed a repeated negative compensation for cold acclimation. The constancy of the break in the Arrhenius plot of liver cytochrome oxidase (EC 1.9.3.1) was consistent with the lack of homeoviscous adaptation of membrane lipids. A thermoadaptive strategy based on the reduction of sea bass metabolic activity is suggested. PMID- 1406067 TI - Improved resolution of 31P nuclear magnetic resonance spectra of phospholipids from brain. AB - A method is described wherein the resolution of 31P nuclear magnetic resonance spectra of the lipophilic fraction from a Bligh-Dyer extract of rat brain can be enhanced. The lipids are dispersed as micelles in aqueous solution with sodium deoxycholate, and spectral resolution is further optimized by adjusting the pH and by removing ions from the solution. The application of the method to the study of aging in rat brain serves as an example. PMID- 1406068 TI - One-step synthesis of radioactive acyl-CoA and acylcarnitines using rat liver mitochondrial outer membrane as enzyme source. AB - Rat liver mitochondrial outer membrane enriched preparations have proven to be a convenient enzyme source for synthesizing coenzyme A (CoA) and carnitine esters of radioactive fatty acids. These membranes are simple to isolate and they retain acyl-CoA ligase and carnitine palmitoyltransferase activities well upon storage. Enzyme purification is not required. A novel aspect of the present procedure is that the same enzymatic incubation step allows both the acyl-CoA and the acylcarnitine esters to be obtained simultaneously when carnitine is present, but produces acyl-CoA ester only when carnitine is not included. Under the conditions described, the conversion of [1-14C]octanoic acid to the respective esters was about 95%; the corresponding figure for [1-14C]palmitic acids was over 70%. The procedure seems suitable for synthesizing the labeled CoA and carnitine esters from a variety of radioactive fatty acids. PMID- 1406069 TI - The origin of palmitic acid in brain of the developing rat. AB - A rat milk substitute containing lower amounts of palmitic and oleic acid in the triacylglycerols in comparison to natural rat milk was fed to artificially reared rat pups from day 7 after birth to day 14. Pups reared by their mother served as controls. Free trideuterated (D3) palmitic acid [(C2H3)(CH2)14COOH, 98 atom % D] and free perdeuterated (D31) palmitic acid [C15(2)H31COOH, 99 atom % D] in equal quantity were mixed into the triacylglycerols of the milk substitute in an amount equal to 100% of the palmitic acid in the triacylglycerols. A control milk substitute contained unlabeled free palmitic acid in an amount equal to 100% of the palmitic acid in the triacylglycerols of the milk substitute. The objective was to determine if palmitic acid in the diet contributed significantly to the palmitic acid content of developing brain and other organs. The methyl esters of the fatty acids were analyzed by gas chromatography and the palmitic acid methyl ester was examined by fast atom bombardment mass spectrometry. The proportion of deuterated methyl palmitate as a percentage of total palmitate was determined; 32% of the palmitic acid in liver and 12% of the palmitic acid in lung were trideuterated and perdeuterated palmitic acid in approximately equal amounts. The brain, by contrast, did not contain the deuterated palmitic acid moiety. Quantitation of palmitic acid and total fatty acids revealed a significant accumulation in organs in the interval from 7 to 14 days of age. Under our experimental conditions, labeled palmitic acid does not enter the brain. Consequently, we conclude that the developing brain produces all required palmitic acid by de novo synthesis. PMID- 1406070 TI - Glucocorticoid and mineralocorticoid hormones depress liver delta 5 desaturase activity through different mechanisms. AB - The effects of 11-deoxycorticosterone and aldosterone on liver delta 5 desaturase activity were examined. Both steroid hormones significantly depressed the conversion of [1-14C] eicosatrienoic acid to arachidonic acid. However, the mechanism of action of each of these hormones was different. The effect of 11 deoxycorticosterone was mediated by a soluble protein present in the liver cytosolic fraction. The biological activity of this protein, having a molecular weight lower than 25 kDa, was impaired by trypsin digestion. To determine whether the inhibitory protein was induced through glucocorticoid or mineralocorticoid receptor occupancy, cultured Morris minimal deviation hepatoma cells were pre treated with the antiglucocorticoid cortexolone or the mineralocorticoid receptor antagonist spironolactone. The results obtained demonstrated that only glucocorticoid receptor structures were involved in the induction of this regulatory protein. The inhibitory response evoked by aldosterone was mediated by a different mechanism. In the case of aldosterone, the inhibitory action affected the microsomal membranes and was not mediated by a soluble protein messenger. PMID- 1406072 TI - Surface components of chylomicrons from rats fed glyceryl or alkyl esters of fatty acids: minor components. AB - The lipid class, fatty acid and molecular species composition of the minor polar surface components of rat lymph chylomicrons were determined during absorption of menhaden oil and corn oil or of the corresponding fatty acid ethyl esters. In addition to the previously reported minor polar lipids (sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidic acid and lysophosphatidylcholine), we identified phosphatidylglycerol, dimethylphosphatidylethanolamine, ceramide and cholesteryl sulfate in the chylomicrons from both oil and ester feeding. The dietary fatty acids were found to be incorporated to a variable extent into the different phospholipid classes, the proportions of which remained the same during both types of feeding. No evidence was obtained for the presence of the minor glycerophospholipids characteristic of the lysosomal membranes (e.g., bis-phosphatidic, lysobisphosphatidic and semilysobis-phosphatidic acids), although special efforts were made to identify them. These results indicate that the chylomicrons arising from the monoacylglycerol and phosphatidic acid pathways of triacylglycerol biosynthesis become enveloped in closely similar monolayers of phospholipids. Hence, all triacylglycerols may be secreted from the villus cells via a common mechanism as suggested by the previously demonstrated convergence (at the 2 monoacylglycerol stage) of the monoacylglycerol and the phosphatidic acid pathways of mucosal triacylglycerol formation [Yang, Y.L., and Kuksis, A. (1991) J. Lipid Res. 32, 1173-1186]. PMID- 1406071 TI - Effects of various dietary fats on cardiolipin acyl composition during ontogeny of mice. AB - Cardiolipin (CL) is a unique mitochondrial phospholipid, containing up to 85 wt% 18:2n-6 in mammals. The influence of maternal dietary fatty acids on the acyl composition of offspring CL has not been examined previously. Adult female mice were thus fed diets rich in 18:1n-9 (olive oil), 18:2n-6 (safflower oil), 18:3n-3 (linseed oil) or 20:5n-3 and 22:6n-3 (fish oil/safflower, 9:1, w/w), for a five month period, encompassing two breeding cycles. Offspring from the second breeding cycle were then fed these diets. The acyl composition of CL, phosphatidylcholine and phosphatidylethanolamine from liver and heart was evaluated from mice killed 3, 18 and 42 days after parturition. The primary nutrient sources at these three time points were transplacental nutrients, breast milk and the diet, respectively. Maternal diet was found to influence the acyl composition of CL via both placental transfer of fatty acids and breast milk. Fish oil feeding resulted in replacement of a substantial portion of 18:2n-6 with 22:6n-3; after 42 days, the area% of 18:2n-6 in heart CL was reduced from 62% in safflower oil fed mice to 12%. In comparison to fish oil feeding, linseed oil feeding resulted in a much lower accumulation of 22:6n-3. Olive oil feeding resulted in substantial replacement of 18:2n-6 with 18:1n-9 (18:2n-6 was reduced from 62% to 31%). Physiologically, these findings are relevant because changes in CL acyl composition may influence the activity of associated inner mitochondrial membrane enzymes. PMID- 1406073 TI - Increments of dietary linoleate raise liver arachidonate, but markedly reduce heart n-6 and n-3 fatty acids in the rat. AB - Four diets containing 20% of energy (en%) as fat and with linoleic acid contents of 1.9, 3.1, 7.7 and 10.1 en%, respectively, were fed to one-month-old male rats for three months. The fatty acid profiles and the levels of the major n-6 and n-3 fatty acids in the lipids of plasma, liver, heart and kidney were measured. We found that with increasing concentrations of 18:2n-6 in the diet, linoleic acid rose in plasma and in all organs, but long-chain n-6 and n-3 fatty acids responded differently. In liver, arachidonic acid increased and n-3 fatty acids were not significantly affected; in heart, both arachidonic and docosahexaenoic acids were progressively reduced; and in kidney, there was no change of n-6 and n 3. The results indicate that incremental changes in dietary linoleate affect the levels of polyunsaturated fatty acids in liver and extrahepatic organs differently. PMID- 1406074 TI - Incorporation of n-3 fatty acids of fish oil into tissue and serum lipids of ruminants. AB - This study examines the biohydrogenation and utilization of the C20 and C22 polyenoic fatty acids in ruminants. Eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids were not biohydrogenated to any significant extent by rumen microorganisms, whereas C18 polyenoic fatty acids were extensively hydrogenated. The feeding of protected fish oil increased the proportion of 20:5 from 1% to 13-18% and 22:6 from 2% to 7-9% in serum lipids and there were reductions in the proportion of stearic (18:0) and linoleic (18:2) acids. The proportion of 20:5 in muscle phospholipids (PL) increased from 1.5% to 14.7% and 22:6 from 1.0% to 4.2%; these acids were not incorporated into muscle or adipose tissue triacylglycerols (TAG). In the total PL of muscle, the incorporated 20:5 and 22:6 substituted primarily for oleic (18:1) and/or linoleic (18:2) acid, and there was no consistent change in the porportion of arachidonic (20:4) acid. PMID- 1406075 TI - Comparison of sulfoquinovosyl diacylglycerol from spinach and the purple bacterium Rhodobacter spaeroides by fast atom bombardment tandem mass spectrometry. AB - Isolated sulfoquinovosyl-diacylglycerol (SQD) from spinach and the purple bacterium Rhodobacter sphaeroides provide two sources of very different molecular species of SQD. We were able to demonstrate by fast atom bombardment collisionally activated dissociation tandem mass spectrometry in the negative ion mode that the sulfoquinovosyl head group of the plant and bacterial lipids can be characterized by the common fragmentation pattern found in the spectra of both samples. Differences in the acyl functions from the two sources were also identified by this technique. SQD specific fragments are found at m/z 299, 283, 241, 225, 165 and 80 which indicate the presence of the sulfoquinovosyl moiety. The two predominant molecular species found in spinach contain palmitic and linolenic ([M-H]- at m/z 815) or two linolenic acids ([M-H]- at m/z 837) in the sn-1 and sn-2 positions, while the two major species of the bacterial lipid contain palmitic and 18:1 (vaccenic) acids ([M-H]- at m/z 819) or stearic and 18:1 (vaccenic) acids, ([M-H]- at m/z 847), respectively. PMID- 1406076 TI - Positional analyses of triacylglycerol fatty acids in the milk fat of the antarctic fur seal (Arctocephalus gazella). AB - The positional distribution of fatty acids has been determined for the milk triacylglycerols of the Antarctic fur seal, Arctocephalus gazella. Of particular interest was the positional distribution of the polyunsaturated n-3 fatty acids in milk triacylglycerols (TG). In adipocytes of pinnipeds, TG are synthesized with the n-3 fatty acids primarily in the sn-1,3 positions. To determine the positional distribution, extracts of enzymatically digested lipids were separated by thin-layer chromatography, and the constituent fatty acids were separated and quantified by gas-liquid chromatography. Monoenoic and saturated fatty acids comprised over 75% of the total, the ratio of monoenoic to saturated fatty acids being 2:1. The percent content of the long-chain n-3 fatty acids, 20:5, 22:5 and 22:6, ranged between 15-20%. The positional analyses revealed that at the sn-2 position of milk TG, saturated fatty acids were in excess (57%), and the content of n-3 fatty acids was less than 5%. More than 80% of the n-3 fatty acids in milk were located in the sn-1,3 positions. The data indicate that in pinnipeds TG are synthesized in the mammary gland and adipose tissue with fatty acids having similar positional distributions. PMID- 1406077 TI - Ultrastructural aspects of liver injury with special reference to small bile ducts in patients with ulcerative colitis. AB - Liver tissue specimens taken at colectomy from 29 patients with chronic ulcerative colitis were studied by electron microscope. The fine-structural alterations were correlated with light microscopy and with biochemical liver function tests. The purpose was to identify ultrastructural features which could explain the pathogenesis of sclerosing cholangitis. Severely injured bile-duct epithelial cells were seen in three out of the eight light-microscopically diagnosed cholangitis cases, in the two cases of non-specific reactive hepatitis, and in the two fatty livers. Four cholangitis cases had, in heavily thickened bile-duct basement membranes, translucent areas containing bile-like material. Bile-duct microvilli were often blunted, and reduced in number. Intracanalicular bile thrombi and bile inclusions in hepatocytes were seldom seen, mostly but not exclusively in cholangitis. The fine-structural alterations apparently represent various stages of liver injury. These findings do not appear to be specific, but their prominence seems to correlate with the progression of the disease, at least in the case of histological parameters, but also in serum enzyme activities indicative of cholestasis. The bile-like electron-dense material found in proliferating basement membranes, very possibly regurgitated into the injured bile-duct wall after epithelial injury, could enhance the development of periductal fibrosis, leading to progression of sclerosing cholangitis. PMID- 1406078 TI - Peripheral blood lymphocyte subsets in patients with chronic hepatitis C--effects of interferon treatment. AB - Thirty-three patients with chronic hepatitis non-A, non-B/C were included in a randomized controlled study of recombinant alpha-2b interferon treatment 3 MU three times weekly for 36 weeks. In lysed whole blood, lymphocyte subpopulations were enumerated by flow cytometry detecting fluorescein or phycoerytrin conjugated monoclonal antibodies directed against seven different epitopes. Patients with chronic active hepatitis were significantly older than patients with chronic persistent hepatitis (p less than 0.05). Before treatment, the proportions of different subsets of lymphocytes were within the normal reference values and the CD4/CD8 ratio was also normal. No increased activation of T-cells was noticed. Patients over 50 years of age, however, had a significantly increased (p less than 0.01) proportion of HLA-DR+ lymphocytes, mainly B-cells. Treatment decreased the absolute number of peripheral blood leukocytes and lymphocytes. There was also a significant decline in the proportion of CD8+ lymphocytes and NK-cells, and a significant increase in the proportion HLA-DR+ cells and of the CD4/CD8 ratio. The increased proportion of HLA-DR+ cells, however, did not reflect peripheral T-cell activation; instead, it was due to increasing B lymphocyte numbers. PMID- 1406080 TI - Haemodynamic alterations and their morphological basis in biliary obstruction. AB - The relationship between the haemodynamic alterations and morphological changes in the liver caused by biliary obstruction was investigated in rats after ligation of the common bile duct. In these rats, the portal vein pressure was markedly elevated, and the differences in blood pressure between the portal vein and the terminal portal venule and between the terminal portal venule and the terminal hepatic venule were greater than in the sham-operated rat. The livers showed narrowing of the most peripheral branches of the portal vein due to compression by proliferated bile ductules and sinusoidal stenosis due to enlarged liver cells, but there was no perceptible change in the hepatic vein branches. These data suggest that hepatic circulatory disturbance in biliary obstruction is caused by deformation of the peripheral portal vein branches and sinusoidal stenosis. PMID- 1406079 TI - Modulation of thioacetamide-induced hepatocellular necrosis by prostaglandins is associated with novel histologic changes. AB - Cytoprotective effects of the prostaglandins 16,16-dimethyl PGE2 (dmPGE2) and PGF2 alpha tromethamine (PGF2 alpha) were evaluated in the rat model of acute hepatocellular necrosis induced by thioacetamide (TAA). dmPGE2 (100 micrograms/kg SC 8 hourly) did not induce a significant increase in survival when started after the onset of TAA-induced fulminant hepatic failure. However, priming with dmPGE2 (100 micrograms/kg SC 30 min before TAA) reduced TAA-induced elevations in serum ALT (684 +/- 68 (SEM) vs 274 +/- 135 IU/1, p less than 0.01). This phenomenon did not occur if dmPGE2 was administered after TAA or by the IP route. Modulation of TAA-induced centrizonal hepatocellular necrosis by dmPGE2 was associated with a striking increase in centrizonal ballooning of hepatocytes (p less than 0.01), and, as assessed by stereology, less hepatocellular necrosis and degenerative changes. PGF2 alpha, which in contrast to dmPGE2 does not act via cAMP, had no effect on TAA-induced changes in serum ALT or hepatic histology. These findings suggest that dmPGE2 decreases hepatocellular necrosis by activating surface membrane adenylate cyclase and consequently stimulating cAMP. Ballooning of hepatocytes could occur secondary to these membrane events and appears to be a marker of dmPGE2-induced cytoprotection in this model. PMID- 1406081 TI - An enzyme-linked (alkaline phosphatase) oligonucleotide probe for the detection of serum hepatitis B virus DNA. AB - Serum HBV-DNA detection represents a new and important diagnostic tool for the hepatologist, as well as a prognostic and therapeutic guide. Though most laboratories use genomic radioactive probes, the appearance of commercially available enzyme-linked oligonucleotide probes, which simplify the method, represents an advance in HBV-DNA detection. In order to verify the value of an enzyme-linked (alkaline phosphatase) oligonucleotide probe in HBV-DNA detection, we have first compared the results of the detection of serum HBV-DNA in 46 patients at different serological stages of HBV infection using this probe and with those obtained using a genomic P32-labeled probe. Fisher's test analysis of the results shows statistical significance; this indicates a high correlation between methods. Secondly, we have tested 296 sera of patients at different serological stages of HBV infection with the enzyme-linked probe; we have found HBV-DNA in 8 patients with acute hepatitis (61.54%), 61 HBeAg (70.12%), and 7 anti-HBe (12.07%) chronic hepatitis. These results show the value of this probe for routine survey of serum HBV-DNA using a simple method which avoids the use of radioactivity. PMID- 1406082 TI - Intracellular distribution and effect of the antimalarial drug mefloquine on lysosomes of rat liver. AB - Mefloquine was administered in a single dose (1-30 mg/100 g) to rats in order to study its subcellular distribution and effects on rat liver lysosomal structure and function. Subcellular fractionation showed a significant enrichment of mefloquine in lysosomes. Even repeated administration of mefloquine did not affect the levels of cytochrome-P-450 or its reductase, indicating, although not proving, that it is not metabolized by this mono-oxygenase system. Mefloquine caused an expansion of the lysosomal apparatus, earliest seen by 24 h and lasting for some 7 days. Initially, cytoplasmic constituents were seen inside the lysosomes. Later, the lysosomes harboured myelin-like figures (multilamellar bodies) disappearing after 7-10 days. The proteolytic and lipolytic capacity was assessed in isolated lysosomes. Mefloquine caused increased protein degradation but decreased breakdown of lipids. Concomitantly, all five major phospholipids (phosphatidyl-choline, -ethanolamine, -inositol, -serine and sphingomyelin) increased in the lysosomes. It is concluded that: (1) mefloquine is a lysosomotropic drug that accumulates in lysosomes; (2) mefloquine impairs lipid degradation with ensuing accumulation of lipids in lysosomes; and (3) lysosomal trapping explains the high volume distribution of mefloquine. PMID- 1406083 TI - Quantitative analysis of activated Kupffer cells in viral hepatitis: application of computer image analysis for lectin histochemistry. AB - Lectin histochemistry revealed that Kupffer cells in the normal liver bound lectins such as Concanavalin A (Con A), Ricinus communis agglutinin (RCA) and Wheat germ agglutinin (WGA), but did not bind Peanut agglutinin (PNA), Dolichos fibflorus agglutinin (DBA), Ulex europaeus agglutinin I (UEA-I) or Soybean agglutinin (SBA). Kupffer cells in viral liver diseases, however, bound the PNA lectin and the binding was specific to Kupffer cells in liver parenchyma. Computer image analysis was performed using light micrographs of sections stained with immunoperoxidase and diaminobenzidine (DAB). The dark brown area of reaction products was detected by analyzing each color component (red, green and blue) in the picture and was expressed as the percent area in the parenchyma. Quantitative analysis revealed the percent area occupied by Kupffer cells positive for the PNA lectin was as follows: acute hepatitis, 2.83 +/- 0.74; chronic persistent hepatitis, 2.51 +/- 0.88; chronic aggressive hepatitis, activity moderate and severe, 4.71 +/- 2.23 and 3.45 +/- 1.84; and liver cirrhosis, 1.96 +/- 0.99. The percent area of Kupffer cells was significantly higher in CAH2A than that in chronic persistent hepatitis or in liver cirrhosis. These results suggest that the PNA lectin could be used as a marker for activated Kupffer cells and that activated Kupffer cells were increased in volume in chronic aggressive hepatitis. PMID- 1406084 TI - Breast disease evaluation with fat-suppressed magnetic resonance imaging. AB - Thirty patients with a variety of pathologically confirmed malignant and benign pathologic lesions of the breast were evaluated with a spectrally selective fat suppression imaging technique to obtain fat-suppressed images of the breast. The technique, a selective partial inversion-recovery (SPIR) method, demonstrated the architectural relationship of malignant and benign tumors with respect to the normal water-containing elements of the breast. These relationships included signs of advanced malignant disease such as tissue retraction, invasive growth, and multicentricity, which appeared on the fat-suppressed images. Fat-suppressed imaging provided useful information for assessing the breasts of both pre- and postmenopausal women, especially in the latter group, where fatty involution of the breast is common. Microcysts, which are normally not visualized by conventional methods, were demonstrated and associated with patients having confirmed fibrocystic disease of the breast. As expected, the SPIR technique did not improve the ability to distinguish between tissues having similar T1 and T2 relaxation time values, such as malignant tumors and normal breast parenchymal tissues. The technique was able to demonstrate that the intense lipid signal, known to be responsible for obscuring the borders of water-fat interfaces and small tumors, could be eliminated in a variety of pathological settings. PMID- 1406085 TI - Heterogeneous in vivo MR images of soft tissue tumors: guide to gross specimen sampling. AB - Twelve soft tissue tumors preoperatively studied with magnetic resonance (MR) imaging contained areas of inhomogeneous intralesional signal intensity. The pathologist's selection of biopsy sites from gross specimens was based on specific MR images selected by a radiologist and depended on close cooperation between the radiologist and pathologist. The histopathology so sampled, further depended on the lesion's size, careful gross specimen orientation, discrete sampling, and a specially developed Grid Analysis technique. Our initial experience indicates that (1) histology may vary within different and often neighboring sites of a single soft tissue lesion; (2) that such variability is common in soft tissue tumors; (3) that histological variability within different sites of a single lesion influences signal heterogeneity; and (4) that although differing MR signal intensities per se are not tissue specific, MR may enhance the histopathological accuracy of pathologists who can be directed to particular gross specimen sites by magnetic resonance images. To our knowledge such a specific, detailed effort has not been made. PMID- 1406086 TI - Magnetization transfer contrast imaging of the human leg at 0.1 T: a preliminary study. AB - Magnetization transfer contrast imaging is an MR technique that capitalizes on interactions between the protons of mobile and macromolecularly bound water molecules. Studies to date, conducted primarily on 4.7 T and 1.5 T MR systems, have yielded results unique from conventional T1- and T2-weighted imaging studies. In this study, performed on a 0.1 T device, a section of lower leg was imaged in 20 normal human subjects and one patient with muscular dystrophy, using both a standard 500/22 gradient-echo sequence and a 500/22 gradient-echo sequence combined with off-resonance radio frequency irradiation designed to elicit magnetization transfer contrast. Results of the two techniques were compared. Our findings suggest that magnetization transfer contrast imaging is feasible at 0.1 T, and that this technique allows reproducible tissue characterization and improves contrast between certain tissues. PMID- 1406087 TI - On the relation between the dimensions and resonance characteristics of the vocal tract: a study with MRI. AB - The relation between the spatial configuration of the vocal tract as determined by magnetic resonance imaging (MRI) and the acoustical signal produced was investigated. A male subject carried out a set of phonatory tasks, comprising the utterance of the sustained vowels /i/ and /a/, each in a single articulation, and the vowel /epsilon/ with his larynx positioned variously on a vertical axis. Two- and three-dimensional measurements of the vocal tract were performed. The results of these measurements were used to calculate resonance frequencies, according to predictions from acoustical theory. Finally, calculated frequencies were compared with actually measured resonance frequencies in the audio signal. We found a strong relation between the acoustical signal produced and the spatial configuration for the first resonance frequencies of the articulations of the vowel /epsilon/, and first two resonance frequencies of the vowels /a/ and /i/. The capability to determine accurately vocal tract dimensions is a major advantage of this imaging technique. PMID- 1406088 TI - Thymidine-modulated 5-fluorouracil metabolism in liver and RIF-1 tumors studied by 19F magnetic resonance spectroscopy. AB - 19F Magnetic resonance spectroscopy was used to study the impact of the biochemical modulator thymidine (TdR) on the 5-fluorouracil (5FU) metabolism in the livers and radiation-induced fibrosarcoma (RIF-1) tumors of 5FU-treated C3H mice. The liver spectra measured after administration of 5FU (65 or 130 mg/kg IP) showed the 5 FU resonance and its catabolites alpha-fluoro-beta-ureidopropionic acid and alpha-fluoro-beta-alanine. At the latter dose, fluoronucleotide signal was also detected. The liver spectra of TdR-pretreated (500 mg/kg, IP) mice showed additional signals of fluoronucleotide and fluoronucleoside at both 5FU doses, while alpha-fluoro-beta-alanine was not detected. TdR pretreatment increased the half-life of 5FU in livers from 24 +/- 2 to 126 +/- 46 SEM min at the 5FU dose of 65 mg/kg and from 28 +/- 2 to 95 +/- 22 min at the 130 mg/kg dose (P less than .1 and P less than .01, respectively). TdR-pretreated mice had higher 5FU anabolite (fluoronucleotide + fluoronucleoside) levels in their RIF-1 tumors than nonpretreated mice that received the same 5FU doses (56 +/- 15 SEM vs. 0 arbitrary units at the 5FU dose of 65 mg/kg, and 88 +/- 21 vs. 10 +/- 3 arbitrary units at 130 mg/kg 5FU; P less than .0001). The percentage drop in tumor volume was enhanced in the mice that received TdR, from 27 +/- 4 SEM to 52 +/- 2 at the 5 FU dose of 65 mg/kg and from 24 +/- 3 to 65 +/- 4 at the 130-mg/kg dose (P less than .0001, both). PMID- 1406089 TI - In vitro NMR investigation of controlled single and repeated isoflurane anesthesia. AB - Immobilization of laboratory animals is a basic requirement for experimental in vivo NMR measurements. The effect of single and repeated isoflurane anesthesia on proton NMR relaxation times T1 and T2 in rat liver was studied. Furthermore, physiological monitoring was performed to evaluate the influence of isoflurane anesthesia (up to 2 hr) on biological parameters. Neither single nor repeated isoflurane application over the observed time produce relevant alterations of physiological parameters or relaxation times, compared with untreated control groups. Therefore, we conclude that isoflurane anesthesia is appropriate for in vivo NMR investigations, especially of the liver. PMID- 1406090 TI - Explicit treatment of mutual inductance in eight-column birdcage resonators. AB - A formulation has been developed for the determination of self and mutual inductances in unloaded, eight-column symmetric birdcage coils using their expected resonant mode current patterns and well-known inductance formulas. The average frequency differences between theory and experiment for mode one resonances for nine low-pass coils were 0.66 (+/- 0.57) MHz and 2.14 (+/- 2.08) MHz using effective (self plus mutual) and self inductances, respectively, and similarly, for three high-pass coils, 1.19 (+/- 0.56) MHz and 2.79 (+/- 2.20) MHz. These frequency differences were more pronounced for the higher modes; for mode four, the differences neglecting mutual inductance were 14.30 (+/- 11.10) MHz and 10.42 (+/- 4.60) MHz for the low- and high-pass coils, respectively. This analysis provides the first explicit evaluation of the total end-ring and column inductances L1 and L2 within each birdcage section at resonance with resulting excellent agreement in resonant frequencies between theory and experiment. PMID- 1406091 TI - Purpose-designed probes and their applications for dynamic NMR microscopy in an electromagnet. AB - The electromagnet provides a favorable environment for certain applications of NMR microscopy. These include plant imaging experiments and measurements of slow molecular diffusion, where high magnetic field gradients for the pulsed gradient spin echo (PGSE) technique are required. In this paper, two probes designed specifically for these two applications are described. In the first case, the open space within the probe has been maximized in order to incorporate environmental support systems for the plant, while in the second the smallest possible PGSE gradient coil former has been used to maximize the gradient strength. Examples are given of Dynamic NMR Microscopy experiments on a castor bean stem and on poly(ethylene oxide)/water solutions under shear thinning conditions. PMID- 1406092 TI - Compression and reconstruction of MRI images using 2D DCT. AB - In magnetic resonance imaging (MRI), the original data are sampled in the spatial frequency domain. The sampled data thus constitute a set of discrete Fourier transform (DFT) coefficients. The image is usually reconstructed by taking inverse DFT. The image data may then be compressed using the discrete cosine transform (DCT). We present here a method of treating the data that combines two procedures, image reconstruction and data compression. This method may be particularly useful in medical picture archiving and communication systems (PACS) where both image reconstruction and compression are important issues. PMID- 1406093 TI - Fetal development of mice following intrauterine exposure to a static magnetic field of 6.3 T. AB - The study was undertaken to investigate possible teratogenic effects of a high magnetic field on fetal development in mice. Eighty-four pregnant CD-1 mice (ICR) were exposed to a static magnetic field of 6.3 T for 1 hr a day from day 7 through day 14 of gestation, a period corresponding to major organogenesis. Fifty mice served as controls. Dams were sacrificed on day 18 of gestation. Fetuses were examined for both external and skeletal abnormalities. No significant differences between exposed and control groups were observed regarding litter size, fetal weight, intrauterine mortality rate, or external and skeletal anomalies. The effects of static magnetic field of 6.3 T on the parameters studied appear negligible. PMID- 1406094 TI - Evaluation of nonionic nitroxyl lipids as potential organ-specific contrast agents for magnetic resonance imaging. AB - Considering their intrinsic properties of accumulation in the hepatic tissue, we have synthesized nitroxyl-containing lipids as potential organ-specific contrast agents for magnetic resonance imaging (MRI). Their resistance to reduction by ascorbate and in liver homogenates, and their relaxivity in different media were investigated and compared to those of free carboxyl-Proxyl (3-carboxy-2,2,5,5 tetramethylpyrrolidine-1-oxyl) and Tempamaine (4-amino-2,2,6,6 tetramethylpiperidine-1-oxyl). With respect to the reduction rates by ascorbate, the lipid derivatives show the same well-known order of reactivity as carboxy Proxyl and Tempamine, the five-membered nitroxyls being more stable than the six membered compounds. However the binding of the piperidinoxyl compounds to the fatty acids confers to those lipid derivatives a markedly increased stability. Similarly, in liver homogenates, the nitroxyl lipids remained unchanged more than 20 min, contrarily to carboxy-Proxyl and Tempamine. The measurements of spin lattice relaxation time (T1) in biological media have demonstrated a higher relaxivity of nitroxyl lipids, which can be related to their interaction with proteins. Tested in vivo, one of the synthesized compounds (0.75 mmol/kg) produced an enhancement of 44 +/- 12% of the hepatic signal 5 min after intraportal injection in T1-weighted images. The potential applicability of the other nitroxyl lipids as contrast agents for MRI was limited in the in vivo studies by an unexpected toxicity. Work is currently in progress to improve the therapeutic index of the present class of nitroxyl lipids. PMID- 1406095 TI - Motion-triggered cine MR imaging of active joint movement. AB - MRI cine studies of active physiological joint movement can provide additional functional information as a supplement to standard examinations. With the ankle joint as an example, it is shown that it is possible to measure kinematic MRI presentations of active joint movement. A pneumatic pressure transducer, a respiratory monitor, and an active differentiator transformed the skin muscle shifting of periodically performed joint movement to a pseudo-ECG, which finally triggered the MRI scanner as in cardiac cine MR imaging. PMID- 1406096 TI - Gradient amplifier imperfections in NMR imaging. AB - This paper describes the influence of the transition distortion of gradient amplifiers on direct Fourier NMR imaging techniques. We demonstrate artifacts arising in the real measurement of the spin density images. Image artifacts are compared with artifacts obtained by computer simulations of the transition distortion of gradient amplifiers. PMID- 1406097 TI - Optimization schemes for selective excitations: application to the DIGGER pulses. AB - In this work, two distinct approaches to the tailoring of selective radiofrequency (RF) pulses were applied to a cos-sinc pulse of the DIGGER sequence used in localized spectroscopy. Ideally, three such pulses combined with a gradient in each direction destroy the Mz component of the magnetization everywhere but in the volume of interest. In the first approach, the optimal RF amplitude modulation is found by minimizing the difference between the ideal and the computed Mz profiles. In the second strategy, the RF pulse envelope is adjusted by optimization of the tip angle profile. Computed slice profiles optimized by each of these methods have been compared to experimental results. Simulations as well as experiments show that the second approach, which optimizes tip angles, is the most efficient. PMID- 1406098 TI - Spectroscopic imaging display and analysis. AB - A system for display of magnetic resonance (MR) spectroscopic imaging (SI) data is described which provides for efficient review and analysis of the multidimensional spectroscopic and spatial data format of this technique. Features include the rapid display of spectra from selected image voxels, formation of spectroscopic images, spectral and image data processing operations, methods for correlating spectroscopic image data with high resolution 1H MR images, and hardcopy facilities. Examples are shown for 31P and 1H spectroscopic imaging studies obtained in human and rat brain. PMID- 1406099 TI - CT and MR appearance of subureteric Teflon and periuretral Teflon migration: a case report. AB - We present the computed tomography (CT) and magnetic resonance (MR) findings of a case in which an adult patient underwent subureteric injection of polytetrafluoroethylene (PTFE; Teflon) (STING) to correct vesicoureteral reflux. We report the appearance of periureteral PTFE migration mimicking cystic pathology. PMID- 1406100 TI - Skeletal muscle lymphoma: MRI evaluation. AB - The magnetic resonance imaging (MRI) features of two cases of malignant lymphoproliferative disease involving skeletal muscle are presented. In both cases involved muscles were quantitatively and subjectively hypointense to fat on T1-weighted spin echo images, hypointense or isointense on T2-weighted spin echo images, and hyperintense on short tau inversion recovery (STIR) images. The findings suggest that lymphoproliferative disease should be considered as an etiology of a skeletal muscle lesion that is hypointense or isointense to fat on T2-weighted spin echo magnetic resonance images. PMID- 1406101 TI - Who's in charge? Guardianships and children. PMID- 1406102 TI - Respiratory syncytial virus and the use of ribavirin. PMID- 1406103 TI - Breast-feeding in the face of adversity. PMID- 1406104 TI - Controversies in caring for the child with a head injury. PMID- 1406105 TI - Enhancing "employability". PMID- 1406106 TI - For those who enjoy variety. PMID- 1406107 TI - Around before the term was coined. PMID- 1406108 TI - Expertise for quality care. PMID- 1406109 TI - Drawing out. Young mothers. PMID- 1406110 TI - Condoms as primary prevention in sexually active women. PMID- 1406111 TI - EPSDT: the law. PMID- 1406112 TI - Burned out? Try a new challenge in rural hospital. PMID- 1406113 TI - A place for infants with HIV. PMID- 1406114 TI - Guidelines for using meta-analysis. PMID- 1406115 TI - Meeting goals with limited financial resources. PMID- 1406116 TI - Lamaze techniques for pediatric pain. PMID- 1406117 TI - More methods for managing shoulder dystocia. PMID- 1406118 TI - More on revised immunization schedules. PMID- 1406119 TI - Acyclovir in the management of chickenpox. PMID- 1406120 TI - Assessment of the quality of teaching. PMID- 1406121 TI - Twelve tips for conducting effective workshops. PMID- 1406123 TI - How we use questionnaires for learner evaluation of clinical experiences. AB - The use of questionnaires incorporating quantitative and qualitative analysis are an integral part of practice when monitoring the learning experience for student nurses on clinical placement. This paper outlines this system in the belief that the information could be helpful to other health professionals who are responsible for monitoring the clinical learning experiences of their students. Reference is made to other systems, such as educational audit, and some of the trends identified in analysing data collected is discussed. Finally, the potential for further developing this system is noted. PMID- 1406122 TI - Medical students' perceptions of themselves and residents as teachers. AB - Eighty-three medical students from one class at the University of Vermont College of Medicine were surveyed as to their perceptions of both themselves and residents as teachers. Sixty seven percent of the students felt that residents played a significant role as teachers during the first clinical year. Students estimated that one-third of their knowledge could be attributed to housestaff teaching. A large majority of students wanted to teach students during medical school (80%) and residency (93%). Ninety percent of students surveyed would participate in a workshop to improve teaching skills prior to beginning residency; of this group, forty nine students ranked the importance of components of a teaching skills workshop. The findings suggest that medical students are interested both in learning teaching skills and teaching during medical school and during residency. PMID- 1406124 TI - Postgraduate teaching audit by peer review of videotape recordings. AB - The effectiveness of peer review in postgraduate medical teaching by hospital consultants using videotape recordings of teaching sessions has been assessed. The technique is useful for routine, infrequent and for 'one off' self-tuition. Participants' assessment of the 'clarity of structure' of teaching sessions and 'abilities to self-analyse' did change but 'mannerisms' did not. PMID- 1406125 TI - How to evaluate educational programmes in the health professions. AB - This paper advocates an alternative approach to the evaluation of educational programmes in the health professions. In the past, effectiveness of programmes has been judged by casual observations, visitation reports by outside experts, student performance at nationwide examinations, systematic surveys and experimental research. Decisions have been made based on either one or more of the above methods. It is being argued that these methods are not always appropriate and mostly inadequate in providing a holistic description and judgement of the educational programme. Social science disciplines have contributed to the development of case study, an alternative methodology, for evaluating educational programmes. The case study design is emerging as a legitimate approach for evaluating educational programmes. Qualitative methods such as participant observation, interviewing and documentary analysis have been found to bring new insights in evaluating short-term and long-term programmes in medical and allied professions. Although qualitative methods are emphasized in case studies, quantitative data from survey instruments can increase the credibility and understanding of the evaluation results. Different measures have been suggested to deal with questions of validity and reliability in case study evaluation. PMID- 1406126 TI - Senior medical students as simulated patients in an objective structured clinical examination: motivation and benefits. AB - Third and fourth year medical students were recruited to participate as simulated patients and examiners in an Objective Structured Clinical Examination (OSCE) administered for second year medical students. Students reported they were motivated to participate, not only by the honorarium, but because they believed the OSCE would be fun and interesting and because they were interested in medical education and in improving clinical evaluation. The third and fourth year medical students benefitted academically and financially from participation. Faculty benefitted by having a readily available source of enthusiastic and knowledgeable simulated patients. PMID- 1406127 TI - An examination of the examinations: the reliability of the objective structured clinical examination and clinical examination. AB - This study evaluates the correlation that exists between the objective structured clinical examination and the traditional clinical examination. An analysis is performed on the results of four groups of students assessed by these two methods. The internal consistency of the OSCE is also described by correlating the results by rank difference correlation using the split-half method of grading the even and odd numbered stations separately. Also 46 surgical interns were asked to indicate their preference regarding the efficacy of five different methods of assessment of clinical competence. The results indicate a high reliability of OSCE and traditional clinical examination. In the opinion of surgical interns, the OSCE and clinical examination both scored high for their ability to assess clinical competence. PMID- 1406128 TI - Faculty evaluation of student performance: a step toward improving the process. AB - Most clerkship evaluation systems give the greatest evaluative weight in deriving grades to some form of evaluation by faculty and housestaff, although few studies have been reported concerning which elements of performance are most important or which discriminate best. The results of this study show that a select group of faculty, heavily involved with assessment of student performance, agreed that certain aspects of performance were more important and/or discriminated better between average and superior medicine clerks. We suggest that those aspects of performance be given more consideration when designing curricula, providing student feedback, and assigning grades for medicine clerkships and that medical educators engage faculty and housestaff in the formal discussion of issues surrounding evaluation. PMID- 1406129 TI - Profile-based assessment of student project reports. AB - During their final year, medical students at Sheffield University are required to undertake a research or audit project. The students' project reports are assessed using a grid-style criterion-based profile. This is described, and the validity and reliability of this method of summative assessment are discussed. PMID- 1406130 TI - Weightage of formative examinations in certifying examination of pharmacology: an opinion poll and relative performance of learners. AB - A study was carried out to obtain the view points of 186 graduate students regarding formative examination, it's frequency, weightage in certifying examination, feedback about progress made or lack of it and the planning of learning activities. Majority of students were of the opinion that the class tests and tutorials should be conducted frequently and sufficient weightage of formative examinations should be given in the certifying examination. They were able to get feed back and plan out the learning activities accordingly. The performance in both theory and practicals of formative and certifying examinations in Pharmacology was analyzed. The average percentage marks secured by the students in both theory and practical of the certifying examination were higher than those secured in the formative examination. However, the reliability of theory examinations was more than the practical examinations. A positive correlation was observed between the marks of formative and certifying examination between theory as well as of practicals. The Pearson's Correlation Coefficient gamma was +0.932 and +0.715 while Spearman's rank order Coefficient rho was +0.792 and +0.649 for theory and practicals respectively suggesting positive and strong correlation. PMID- 1406131 TI - The multiple choice true/false question: what does it measure and what could it measure? AB - Multiple choice questions of the true/false type are widely used in medical education. Evidence is given which suggests that they only tap a low level of intellectual skill. By using them in a slightly different manner it is suggested that they could be ideal techniques for measuring concept mastery. Some of the consequences of this idea are discussed. PMID- 1406132 TI - Learning contracts in clinical education: evaluation by clinical supervisors. AB - Learning contracts can be a useful learning and evaluation tool within a clinical setting provided the supervisor shifts their role from one of imparter of knowledge to facilitator of learning. If this role is not assumed then a student's learning experience could be jeopardized. In a survey of 59 student supervisors, 90 percent found the learning contract to be a useful evaluation and teaching tool. Advantages stated suggest that the learning contract promotes negotiation between student and teacher, provides a flexible learning environment and promotes acquisition of self-directed learning skills. These qualities are important in a clinical or practical setting where learning experiences cannot be standardized. PMID- 1406133 TI - The survival game. AB - This paper describes a flexible and enjoyable learning game and summarizes our experiences of using it (including the medical students' own evaluation of the game). The description is sufficiently detailed to encourage readers to reproduce and adapt the game to fit their own requirements. PMID- 1406134 TI - Learning objectives in training residents in general surgery in Kuwait. AB - An opinion survey of a five-year postgraduate training programme in general surgery was conducted using a questionnaire. The residents who responded indicated that the use of learning objectives needed to be given greater emphasis. They felt that learning objectives should be more clearly defined and be communicated with the learners and the instructors at an early stage in the programme. While the opportunity for learning theoretical concepts in surgery was rated as a strong feature of the programme, learning practical skills, it was pointed out, needed augmenting. PMID- 1406135 TI - Primary care residency programme evaluation: an analysis of three resident cohorts. AB - The purpose of this study was to conduct a longitudinal evaluation of a university primary care (PC) medical residency programme and use the results to plan for future curriculum development. Overall performance and the ambulatory medical care of three consecutive resident cohorts training from 1982 to 1987 was assessed by attending physicians. PC residents' performance in ambulatory continuity practice was also compared to that of traditional residents' performance in 1985-86. The scoring profile of primary care attendings was compared to that of other attendings. Residents received lowest scores in diagnostic evaluation, leadership and administration. Their best evaluations were in medical care, personal attributes and communication. Two of the three primary care cohorts received lower medical care scores in ambulatory continuity practice compared to other rotations, but had higher overall scores in ambulatory continuity practice than did traditional residents in 1985-86. Primary care attendings gave lower scores to primary care residents than did other faculty. PMID- 1406136 TI - How I teach medical students as an attending physician. AB - The General Professional Education of the Physician (GPEP) Report (1984) recommended a major re-examination of the clinical clerkship, so that medical students could master the basic skills of medicine before graduation. These include clinical observation, interviewing, physical examination, and problem solving skills. This essay discusses the teaching approach of one attending physician during the third year ward clerkship in pediatrics. It describes how many of the goals of clinical medical education can be accomplished during the clerkship in a practical, realistic way. It is the only description about what happens during the teaching sessions of a clinical clerkship on a day by day basis in the medical literature. This approach may serve as a model for clinical teachers of medicine in the organization and planning of the clerkship experience. PMID- 1406138 TI - The cryptic school of time wasting techniques. PMID- 1406137 TI - Does incourse assessment and counselling improve exist performance? AB - Based on an incourse MCQ test in obstetrics and gynaecology, 60 final year medical students were individually advised, according to their performance, whether or not they needed to work harder at the subject to avoid the risk of failure at the final medical examination. Nobody who performed well at the MCQ failed or was borderline at the final examination. Half of those who were advised to work harder occupied the lowest marks at the final examination. The incourse MCQ was sensitive in selecting out those candidates at risk in their final examination but the advice they were given failed to deal with the deficiencies in half of the students involved. After graduating, these doctors will presumably need special help to maintain their knowledge as they are either incapable of self-motivation or are otherwise deficient. The incourse assessment feedback may have helped another small groups of students to work harder but this study cannot confirm that. The exercise seems worthwhile in that the outlay in time is small, there may be a positive advantage for some students and the medical teacher can feel free of any guilt for failing to advise those students who were at risk of poor performance in the final examination. PMID- 1406139 TI - What's new in education: items of interest to medical educators. PMID- 1406140 TI - Do you know? An opportunity to assess how up-to-date you are with the medical education literature. PMID- 1406141 TI - [Maintenance of the stability of the rate of movement of the emitter in Russian x ray computed tomographs]. PMID- 1406142 TI - [The stability of the properties of electroradiographic plates for medical x-ray diagnosis]. AB - The properties of selenium electrocardiographic plates used for the purposes of medical diagnosis are under discussion. The plates are observed to reveal no noticeable traces of fatigue and to retain constant sensitivity to radiation and radiography in the case of the 5 to 10 minutes' interval between obtaining electroradiograms (ERG) during working hours (7 hours). After the technical resource which is equal to 2000 ERG is over, the radiation sensitivity decreases to 10% and defectiveness does not exceed 25%. The actual expiration date of the plates is between 7 and 9 years without worsening of their properties. The quality of the plates stored for a longer time might deteriorate due to the defect which is attributed to crystallization of the selenium layer. PMID- 1406143 TI - [Leakage radiation from the RUM-17 x-ray apparatus outside the main beam]. AB - The leakage radiation exposure rate was measured outside the main beam of the RUM 17 orthovoltage therapeutic x-ray unit by a 1000 cm3 ionization chamber. The results were corrected according to the detector volume averaging. It has been shown that the relative exposure rate normalized to the beam axis exposure rate does not depend on voltage and filter thickness. It can be represented by the same equation. The most important sources of non-used radiation are leakages from the shield (near the treatment cone connection) and scattering in the plexiglass window of the treatment cone. PMID- 1406144 TI - [Development of the new generation of automated laser computer systems for diagnosis and treatment of stomatologic diseases]. PMID- 1406145 TI - [Construction of calibration curves for processing the results of immunometric analyses]. PMID- 1406146 TI - [New information technology in medicine]. PMID- 1406147 TI - [The EOL trainer for respiratory muscles]. AB - A training equipment for respiratory muscles is suggested. It may create peak load at the initial phase of inspiration and expiration, thereby ensuring less fatiguability of respiratory muscles. The efficacy of the training equipment was estimated by clinical and instrumental methods in a group of 43 patients suffering from chronic bronchitis and compared to that of the throttle type trainer in 36 control patients. External respiratory function, acid-base balance and myocardial contractility were found to be significantly improved in the experimental group as compared to the controls. PMID- 1406148 TI - [The use of a magnetically abrasive finishing for sharpening the blades of medical instruments]. AB - The method of magnetically abrasive working was first tried in medical industry as a finishing operation for the sharpening and removing of burrs from half finished blades manufactured by means of vibration forging. The use of the sets for MAO-M-473 and EU-5 makes it possible to manufacture blades with the cutting edge less than or equal to 3 microns in width. The use of magnetically abrasive sharpening enables one to eliminate electrochemical polishing; excludes the appearance of superficial defects on the worked surface; raises corrosion stability and cyclic longevity of the articles. PMID- 1406149 TI - [Leakage currents of medical electrical equipment]. PMID- 1406150 TI - [An automated method of measuring the area of contrasted bronchi]. AB - An automated method for measuring the area of the contrasted bronchi is described. The method involves two research stages. The first one consists of routine bronchography provided to patients suffering from pulmonary diseases according to indications. The second stage is reduced to the digital treatment of the bronchograms to measure the area of the contrasted bronchi. The method is used for the diagnosis of functional bronchial disorders. The bronchial area was measured on the bronchograms taken at the height of inspiration and expiration. Using the data obtained and the appropriate formula, the so called integral coefficient of bronchial constriction was calculated. It allows functional disorders of bronchial patency to be diagnosed and a quantitative expression of that pathology to be evaluated. PMID- 1406151 TI - [An accelerometric method and equipment for controlling the movement of the head of the human operator]. PMID- 1406152 TI - [Problems of the design of turbine stomatologic tips with light guides]. AB - The systems of turbine stomatologic tips with light guides for local illumination of the tooth area to be treated are analyzed. The basic problems that arise in the elaboration of such systems and the results obtained are specified. The technical characteristics of a halogen mini-lamp to be employed in turbine stomatologic tips are provided. PMID- 1406153 TI - [A set of instruments for abdominal surgery using lasers]. PMID- 1406154 TI - [International IEC and ISO standards of medical technology (for practical use by treatment and preventive organizations, developing organizations and business and manufacturing enterprises]. PMID- 1406155 TI - [Quality control of the equipment in x-ray diagnostic departments]. PMID- 1406156 TI - [Borderline pathology: follow-up study. Preliminary report]. AB - The work is based on the frequent use of the term "borderline" in clinical practice, in spite of the fact that this word still tends to have a controversial and ambiguous meaning. Patients who were admitted to the Psychiatric Clinic at the University of Turin between 1974 and 1980 with diagnoses of borderline pathologies or marginal psychoneurosis were followed-up in the study. The subjects in question were reexamined after an interval of between 8 and 14 years (the majority between 10-12 years). An attempt was made to compare the two diagnoses using DSM III R criteria. Family status and employment were also taken into account. It was observed that the diagnosis of marginal syndromes recorded in the patient's clinical records did not correspond to the DSM III R borderline diagnosis, and rather than referring to a precise syndrome it reflected an area of diagnostic uncertainty. This raises various questions both with regard to the role of psychiatry, and in relation to the incidence of cultural factors in influencing observations. PMID- 1406157 TI - [Clinico-diagnostic criteria of hypochondriac syndromes]. AB - The aim of this study was to examine the vast field of hypochondriac symptoms and to put forward diagnostic criteria following the analysis of recent studies on this topic. The "descriptions" based on DSM III trace a partial and selective picture of hypochondriac disorders which is only applicable to a small group of patients in which "somatic complaints" are emphasised in comparison to other less evident psychological variables. The symptom therefore becomes a sign of a pathology which is not defined according to the same complex of symptoms from which it arose. There is in fact no nosological model of hypochondria: we are only likely to meet a "potential hypochondriac" whose pathological expression is limited to part of the population. PMID- 1406158 TI - [Nosographic problems and clinico-phenomenal characteristics of psychoses in epilepsy]. AB - A critical analysis is made of the published reports on the epidemiologico clinical and etiopathogenetic aspects of psychoses in epilepsy. Having underlined the principal characteristics of this pathology together with the main methodological and descriptive problems which emerge from the studies examined, the paper concludes by stressing the need for an approach based on a multifactorial understanding of the causes of these psychoses. In operative terms it is also necessary to evaluate the role of the predominant risk factors in each individual case. PMID- 1406159 TI - [Relationship between type A behavior and the other risk factors in chronic disease]. AB - The relationship between psychological features and coronary heart disease (CHD) have long been investigated. Type A behaviour consists of psychological, behavioral and cognitive features and represents an important risk factor for CHD. The present report is a review of the international literature on the subject. In particular we have taken into account the relationships among type A and other risk factors and the possible biological mechanisms through which type A behaviour may promote CHD. PMID- 1406160 TI - [Neuroleptic malignant syndrome]. AB - The paper defines neuroleptic malignant syndrome and analyses its incidence, predisposing factors, etiology, pathological anatomy and pathogenetic hypotheses. Symptomatology consists of three principal symptoms: extrapyramidal symptoms, hyperthermia, deregulation of the autonomic nervous system. The differential diagnosis of other similar conditions is outlined together with a proposal for a treatment protocol. Emphasis is laid on the importance of prevention. PMID- 1406161 TI - [Evaluation of effectiveness and tolerance of the long-term treatment with bromoperidol decanoate in psychotic disorders]. AB - An open study in 20 patients (7 M, 13 F, mean age 40 years) has been performed in order to evaluate the effectiveness and the safety of bromperidol decanoate in the long-term treatment of psychotic disorders. Patients were selected according to DSM-III-R diagnostic criteria (schizophrenia, residual type: 6 patients; disorganized type: 4; paranoid type: 5; undifferentiated type: 2; atypical psychosis: 3) and treated with bromperidol decanoate 150 mg i.m. (single administration) every month for 6 months. The BPRS scores significantly decreased at the end of the therapy with respect to the beginning (-39.5%; p less than 0.01 Friedman analysis between times); this improvement was already significant at the first month control. The results obtained from a clinical global impression, evaluated from the Visual Analogical Scale (VAS), showed that all patients improved at the end of the therapy (p less than 0.01 ANOVA between times). The side effects, mainly extrapyramidal ones, were mild and did not interfere with the therapy; in fact none patient dropped-out from the treatment. Bromperidol decanoate showed to have a good efficacy and safety in the therapy of psychotic disorders, with a stabilizing effect on the depressive mood. PMID- 1406162 TI - [First applications of a new projective-semantic test. Various considerations on standardization in a sample of adolescents]. AB - Giuseppe R. Brera's B-test was used in a group of students from upper secondary school (102 male adolescents and 86 females) in order to carry out a preliminary standardisation in centiles and to assess the pattern of the seven scales of the test: mood, anxiety, interpersonal affectivity, sociability, autonomy of ego, strength of ego and guilt in adolescents. Factorial analysis by multiple correspondence was used in the same group of adolescents, with the exception of a subgroup of 20 14-year-old students from lower secondary school. The latter was carried out to assess the efficacy of the test in identifying groups of adolescents using the standard association of positive or negative methods of presenting the 44 variables and the free replies to the questions: what do you dream about, what do you look at, what do you advise. Standardisation in centiles allowed indicative risk scores for mental health to be defined for each factor, with the exception of the anxiety factor in males which appears to be a relatively widespread phenomenon in adolescent. Fewer adolescent females suffer from problems of depression, anxiety, interpersonal affectivity and sociability, whereas adolescent males present a smaller number of problems related to the autonomy of the ego, the strength of the ego and guilt. In line with previous works, the test identified 26% of adolescent males and 23% of adolescent females suffering from various in terms of the mean scores from the different factors. For the first time to our knowledge, multiple correspondence analysis identified nine groups of adolescents distributed along two factorial axes: 1 = mood, 2 = interpersonal affectivity. Groups 1 and 2 were characterized by being contrary to the other negative methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406163 TI - [Discussion groups with chronic psychotics in the context of community therapy]. AB - The paper describes the Authors clinical experience of "discussion groups" with psychotic patients. Attention is focused on the problems arising from the community therapy context, the general layout of the setting, the definition of objectives and methods, and in particular the attitude of group leaders. PMID- 1406164 TI - [Art therapy and chronic schizophrenia. Reflections on various aspects of social feelings and the creative self]. AB - The Authors comment on the use of art therapy in a group of institutionalised chronic schizophrenic patients. The aim of these "group interventions" was to encourage the "feeling of belonging" and "creative participation". Artistic expression appears to represent an advantageous method of restoring communication to the schizophrenic. PMID- 1406165 TI - Introduction: exercise and allergy. AB - At a time when the American public is committed to health through exercise, a variety of allergic conditions related to activity are being recognized with increasing frequency. Conditions such as cholinergic urticaria, bronchospasm, and even anaphylaxis have occurred as a consequence of exercise. Thus, a symposium has been developed to examine the role of exercise in association with such conditions. Several of the physical allergies are discussed in overview fashion. Exercise-induced anaphylaxis, the most serious form of allergic response to exercise itself, is considered in greater detail. The etiology, clinical features, and therapy for these physical allergies are addressed. Exercise induced bronchospasm (EIB) has been well categorized in the literature. This is another exercise-related condition with an allergic component. The current concepts with respect to proposed etiology, epidemiology, and clinical features are discussed. EIB is an important condition to screen for, and techniques for identifying patients who should be screened are also addressed. Allergic rhinitis may also affect athletes. Accurate diagnosis and effective management of all these conditions may help greater numbers of people to enjoy the full benefits of exercise. PMID- 1406166 TI - Physical allergies. AB - Allergic responses that occur as a result of exposure to physical stimuli are discussed. Most of these conditions are mediated by vasoactive substances, resulting in urticaria and/or angioedema. Susceptible individuals who engage in athletic activities may place themselves at particular risk for these problems. The physical allergies include cholinergic urticaria, exercise-induced anaphylaxis, cold urticaria, dermatographism, solar urticaria, and aquagenic urticaria. Management of these conditions includes patient education, selective avoidance, antihistamines, and, in some cases, induction of tolerance. PMID- 1406167 TI - Exercise-induced anaphylaxis. AB - Exercise-induced anaphylaxis (EIA) is a unique form of physical allergy that has been recognized with increasing frequency in recent years. The hallmarks of this syndrome are generalized pruritus with a flushing sensation, a feeling of warmth, and the development of urticaria in association with vigorous physical exertion. These symptoms tend to occur variably with exercise, but not with passive warming. Most patients report typical giant urticarial eruptions. Skin mast cells degranulate, and serum histamine increases during symptomatic attacks. Treatment is often problematic, but cessation of exercise with onset of symptoms and self administration of epinephrine are recommended. PMID- 1406168 TI - Exercise-induced bronchospasm: epidemiology, pathophysiology, and therapy. AB - Exercise induced bronchospasm (EIB) is a common clinical problem seen in most individuals with chronic asthma and in nearly half the allergic population. Bronchospasm is typically present 5-15 min after cessation of activity, with spontaneous resolution usually occurring within 20-60 min. The stimulus for EIB is apparently a combination of airway cooling and drying, which results in pulmonary mast cell mediator release. Bronchospasm is generally more severe if there is greater baseline bronchial hyperreactivity or higher intensity of exercise. The treatment of choice for EIB is preexercise administration of a beta adrenergic agonist. Other useful therapies may include cromolyn, theophylline, calcium channel blockers, anticholinergics, and antihistamines. The crucial step for clinicians caring for these patients is making the diagnosis of EIB. The condition responds well to therapy, and treatment may allow for greater enjoyment of activity and enhanced athletic performance. PMID- 1406169 TI - Exercise-induced bronchospasm in the young athlete: guidelines for routine screening and initial management. AB - Exercise induced bronchospasm (EIB) commonly occurs several minutes into or following an exercise event. Respiratory heat loss and respiratory water loss have been suspected as the precursor to exercise-induced bronchospasm. Obstructive EIB has been reported in elite Olympic athletes as well as the recreational athlete. Although exercise-induced bronchospasm presents as wheezing, chest tightness, or dizziness during or after exercise, cough post exercise is a common and an easily detected characteristic of EIB. When exercise induced bronchospasm is suspected in the young athlete, an exercise challenge test should be performed. A 10% or more decrease in the peak expiratory flow rate in the post-exercise period is diagnostic of EIB. Once the diagnosis of EIB has been made, both nonpharmacological and pharmacological interventions are beneficial in reducing the airway responsiveness. Nonpharmacological measures include extensive education and cardiovascular fitness evaluation. Initial pharmacological management should consist of a trial of albuterol inhaler use 15 min prior to exercise. Early identification and treatment of EIB may enhance sports performance as well as enjoyment. PMID- 1406170 TI - Breathlessness predicts perceived exertion in young women with mild asthma. AB - We examined ratings of breathlessness (BRE) as a predictor of perceived exertion (RPE) during incremental cycling at power outputs of 50, 75, and 100 W. Young females (21 yr +/- 1.9) diagnosed with mild asthma (N = 25) were compared with females having normal lung function (N = 25) matched for age, VO2peak, trait anxiety, activity history (7-d recall), and BMI (kg.m-2). Relative oxygen consumption (%VO2peak), blood lactate concentration, VE.VO2(-1), and state anxiety were statistically controlled in hierarchical multiple linear regression analyses. For each group, %VO2peak explained 60% of the variance in RPE across power outputs (P less than 0.001); R2 was unchanged (P greater than 0.10) with the addition of blood lactate, VE.VO2(-1), and state anxiety. Absolute RPE and BRE did not differ between groups at any power output, but partial standardized (beta) and unstandardized (b) regression coefficients and increases in R2 showed that BRE had a greater effect (P less than 0.01) on RPE for asthmatics [adjusted R2 increased to 0.89; (beta) = 0.75; (b) = 0.79 +/- 0.06] than for controls [adjusted R2 increased to 0.74; (beta) = 0.52; (b) = 0.51 +/- 0.09]. The standard error of the prediction was 0.79 for asthmatics and 1.16 for controls. The prediction of RPE by BRE was not moderated by variation in forced expiratory volume for 1 s (FEV1), forced vital capacity (FVC) or peak inspiratory flow (VI). Physiological responses were similar for the groups, but blood lactate was higher in asthmatics at rest, at each power output, and at VO2peak.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406171 TI - Maternal respiration and blood gases during aerobic exercise performed at moderate altitude. AB - We studied whether maternal acid-base status during aerobic exercise performed at moderate altitude is affected by pregnancy. Seven primiparus women were tested at 37 wk gestation and 12 wk postpartum. Subjects were studied at rest, and during two cycle (50 W, 75 W) and two treadmill (67 m.min-1; 2.5% grade, 67 m.min-1; 12% grade) protocols. Exercise bouts lasted 6 min with a 10-min rest between sessions. Minute (VE) and alveolar (VA) ventilation, tidal volume (VT), and ventilatory equivalent for carbon dioxide (VE/VCO2) were significantly (P less than 0.01) greater when exercise was performed during pregnancy. Physiological dead space (VD) was not affected by pregnancy status and did not differ between rest and exercise. Decreases (P less than 0.01) in arterial pH during exercise averaged 0.04 units in both pregnancy and postpartum. Despite similar change in maternal pH, carbon dioxide tension (PaCO2) remained unchanged during exercise at 37 wk gestation but decreased at 12 wk postpartum. Decreases in arterial bicarbonate [HCO3-] associated with exercise were smaller during pregnancy. Our findings indicate that pregnancy did not compromise maternal acid-base status during aerobic exercise. PMID- 1406172 TI - Substrate oxidation and GH responses to exercise are independent of menstrual phase and status. AB - The purpose of this study was to determine the extent to which growth hormone (GH) and energy substrate utilization are influenced by basal sex steroid levels during prolonged submaximal exercise across menstrual phase and status. Also the 17 beta-estradiol (E2) and progesterone responses during prolonged exercise were compared according to menstrual phase and menstrual status. Six amenorrheic (AMc) athletes and seven eumenorrheic (EUc) athletes ran at 60% VO2max for 90 min and serial blood samples were taken at rest, every 10 min throughout exercise, and 5 and 15 min post-exercise. The EUc athletes were tested in the early follicular phase (EF) (days 3-5), the late follicular phase (LF) (days 14-16) and the mid luteal phase (ML) (days 22-25). The incremental GH response to exercise, measured by area under the curve, was consistent with previous reposts and was not altered according to menstrual phase or status (EF-37.5 +/- 11.5, LF-61.9 +/- 11.5, ML 48.1 +/- 12.8 micrograms.1-1.90 min-1). Furthermore, carbohydrate and fat utilization during exercise were not influenced by basal sex steroid levels associated with menstrual phase or status. The incremental E2 response to exercise in AMc athletes was significantly smaller than seen in EUc athletes (AMc 208.1 +/- 44.0, EF-383.0 +/- 116.4, LF-204.7 +/- 84.1, ML-45.1 +/- 18.4 pmol.1( 1).90 min-1), although the pattern of release is similar between groups. In conclusion, GH levels and substrate utilization are independent of both menstrual phase and status; hence, menstrual phase has no negative ramifications on metabolism during exercise. Amenorrhea does not result in metabolic consequences during prolonged exercise by influencing substrate utilization. PMID- 1406173 TI - A weight-lifting exercise model for inducing hypertrophy in the hindlimb muscles of rats. AB - A new method for strength-training of rat hindlimb muscles, comparable to human weight lifting, is compared with sprint training by a treadmill. The new training apparatus that can induce rats to perform human squats was designed. Squat training was composed of isotonic high-intensity, short-duration, and graded overload exercises. After 60 min of one bout of all-out squat and sprint training, serum creatine kinase activities were markedly increased in the squat group (P less than 0.001), but no significant changes were observed in the sprint group. These responses were reflected in the histological sections of the muscles. Some splitting and small fibers were observed only in the squat group, suggesting that different stimulations were applied to the muscles of both the squat and sprint groups. At the end of 12 wk of both types of training, performed 4-5 d.wk-1, the number of fibers in the plantaris muscles of the squat group was greater by 14% than that in the control and sprint groups (P less than 0.001), suggesting hyperplasia following hypertrophy. These results indicated that the muscle strength-training model presented here may provide a new insight into the muscle hypertrophy associated with hyperplasia induced by heavy resistance training. PMID- 1406174 TI - Adrenergic responsiveness and intrinsic sinoatrial automaticity of exercise trained rats. AB - The purpose of this study was to test the hypothesis that bradycardia in exercise trained rats results from decreased intrinsic automaticity of the sinoatrial (SA) node and/or alterations in the responsiveness of the beta-receptors of atrial pacemaker cells. Male Sprague-Dawley rats were divided into exercise trained (ET) and sedentary (SED) groups. ET rats underwent a 12-16 wk program of progressive treadmill training, during which time the SED rats were cage confined. In vivo, resting heart rates were significantly less (P less than 0.05) in ET rats (301 +/ 8 bpm) compared with the SED group (320 +/- 6 bpm). In vitro experiments were conducted on atria isolated from ET and SED rats, and the beta-adrenoceptor agonist isoproterenol was used to investigate cardiac adrenergic control of chronotropic mechanisms in spontaneously beating right atria and inotropic mechanisms in electrically paced (1 Hz) left atria. There were no significant differences between ET and SED cardiac preparations in either the efficacy (maximal response) or potency (EC50) of isoproterenol dose-response relationships for chronotropic or inotropic responses. Intrinsic right atrial beating frequency, measured in the presence of beta-adrenoceptor block by propranolol and cholinergic muscarinic block by atropine, was lower in ET rats. We conclude that training-induced bradycardia in rats is related, at least in part, to alterations in intrinsic automaticity of SA nodal pacemaker tissue, but does not appear to be associated with changes in the properties of the beta 1-adrenoceptors or their affiliated signal transduction mechanisms in either SA pacemaker cells or atrial myocytes. PMID- 1406175 TI - The effects of smokeless tobacco on performance and psychophysiological response. AB - The effects of smokeless tobacco (ST) on psychophysiological response and performance were examined in two studies. Study 1 compared heavy and moderate ST users on psychomotor tasks (simple reaction time/anticipation time and choice reaction time/movement time) in ST (2 g amount) and no smokeless tobacco (NST) conditions. Moderate users performed significantly better than heavy users; there were no significant psychomotor performance differences comparing ST/NST conditions. Heart rate and blood pressure were elevated equally for both groups with the use of ST. Heavy users reported significantly less state anxiety in both ST and NST conditions than moderate users. Study 2 replicated the psychomotor performance results of study 1 when comparing nonusers and ST users who were given four dose amounts of ST (NST, 1/3 mean dose, mean dose, and 5/3 mean) over 4 d. For the math and Stroop tasks, ST use resulted in 12.1% and 10.4% better performance than the NST condition. Physiological measures showed significant elevations during the ST conditions. No differences between dose amounts of ST were apparent for any of the measures. These studies demonstrate that ST users perform better than nonusers when having to react to cognitively challenging task situations. PMID- 1406176 TI - Failure to generalize determinants of self-reported physical activity to a motion sensor. AB - We hypothesized that the prediction of physical activity from psychological determinants would differ when free-living physical activity was assessed by electromechanical or self-report methods. We assessed outcome-expectancy values and perceived barriers for physical activity (OE Values/P Barriers) and physical self-efficacy in 44 young (24 yr +/- 4.8) Caucasian men (N = 13) and women (N = 31). Two weeks later, subjects kept a daily diary and wore a Caltrac motion sensor during all ambulation for seven consecutive days. Reliability (PI) across days was high for MET.h of activity estimated by the diary (0.82) and for Caltrac counts (0.87). Canonical correlation analysis yielded one significant linear combination (Rc = 0.55, P less than 0.01; redundancy = 0.19 to 0.24) of the set of psychological variables [OE Values/P Barriers (beta = 0.76) and physical self efficacy (B = 0.33)] and the set of physical activity estimates [7-d diary (B = 0.89) and Caltrac (beta = 0.24)]. Multiple correlations indicated that the linear combination of OE Values/P Barriers and physical self-efficacy explained 26% of the variation in MET.h reported in the 7-d diary (P less than 0.01) but was unrelated to Caltrac counts (P greater than 0.05). The strongest bivariate model included the 7-d diary and OE Values/P Barriers (r = 0.51, P less than 0.01). Caltrac counts were weakly related to OE Values/P Barriers (r = 0.34, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406177 TI - Effect of manipulation of plasma lactate on integrated EMG during cycling. AB - This investigation was undertaken to record electromyographic activity of the vastus lateralis muscle during incremental cycling exercise and to determine whether it would be sensitive to altered dynamics of plasma lactate increases seen with intense exercise. Trained cyclists (N = 6) performed two progressive, stepwise exercise tests (23.5 W.min-1) to fatigue on a cycle ergometer at 90 rpm. One of the exercise tests was preceded by arm ergometer exercise in an attempt to elevate the circulating plasma lactate levels prior to starting the criterion exercise test. The starting mean plasma lactate values were 4.59 and 26.69 mmol lactate.-1 for the two exercise sessions. Cardiorespiratory values did not differ significantly between exercise sessions completed in the absence and presence of increased circulating plasma lactate. The no-arm trial (i.e., nonelevated plasma lactate condition) was associated with a plasma lactate inflection point (Tlac) at 72.6% VO2max. Previous arm exercise elevated the lactate such that during the criterion exercise plasma lactate values were decreasing with increasing power output at lower exercise intensities. As exercise intensity increased lactate values also increased beginning at a power output of about 76% VO2 max. Mean per cycle integrated EMG (CIEMG) increased linearly with increased power output in both exercise sessions. The slopes of the EMG-power output curve were not significantly different (P less than 0.05). There were no inflection points in these curves. The absence of an inflection point show that surface EMG does not provide an indication of Tlac. PMID- 1406178 TI - Propulsive and gliding phases in four cross-country skiing techniques. AB - The purpose of this study was to compare the relative durations of the propulsive and gliding phases between three skating techniques (1-skate, 2-skate, and offset) and the diagonal stride technique in elite cross-country skiers. Nine skiers of provincial and national level were videotaped with a Panasonic AG 170 camera. The camera speed was set at 30 frames.s-1 and the shutter speed at 1/500 s. The athletes were asked to ski at approximately 80% of their maximal skiing speed on a flat (50 m long) and on an uphill course (35 m long, 5 degrees grade). The relative propulsive phases of the skating techniques were significantly longer than those of the diagonal stride. The relative gliding phases were also longer with the skating techniques. In addition, velocities obtained while skiing with the diagonal stride were about 16% slower than those attained with the skating techniques, principally related to the longer cycle lengths observed with the skating techniques, while cycle rates were quite similar between all four techniques. The results of this study suggest that the longer relative phases of propulsion with the skating techniques may explain the greater speed attained with these techniques in comparison with the diagonal stride. PMID- 1406179 TI - Strength after bouts of eccentric or concentric actions. AB - This study examined the influence of an initial bout of eccentric or concentric actions and a subsequent bout of eccentric actions on muscular strength. Twenty four healthy males, 24-45 yr old, were placed in three groups that performed eccentric actions in bouts 1 and 2 (ECC/ECC, N = 8), concentric actions in bout 1, and eccentric actions in bout 2 (CON/ECC, N = 8) or served as controls (N = 8). Bouts involved unilateral actions with the left and right quadriceps femoris. Ten sets of 10 repetitions with an initial resistance equal to 85% of the eccentric or concentric one repetition maximum (1 RM) were performed for each bout. Three minutes of rest were given between sets and 3 wk between bouts. Two weeks before bout 1 and 1, 4, 7, and 10 d after bouts 1 and 2, eccentric and concentric 1 RM were measured for the right quadriceps femoris and a speed-torque relation established for the left quadriceps femoris. Eccentric and concentric 1 RM decreased (P less than 0.05) 32% 1 d after bout 1 for group ECC/ECC. The speed torque relation was down-shifted (P less than 0.05) 38%. Eccentric 1 RM and eccentric and isometric torque returned to normal 6 d later. Concentric 1 RM and torque at 3.14 rad.s-1 had not recovered on day 10 (-7% for both, P less than 0.05). Decreases in strength after bout 2 for group ECC/ECC only occurred on day (-9% for concentric 1 RM and 16% downshift of the speed-torque relation).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406180 TI - Carbohydrate-electrolyte replacement improves distance running performance in the heat. AB - The effects of a 7% carbohydrate-electrolyte drink (CE) and an artificially sweetened placebo (P) on performance and physiological function were compared during a 40-km run in the heat. Eight highly trained male runners completed two runs on a measured outdoor course. The first 35 km of each run was performed at self-selected training pace and the last 5 km at race effort. Under a counterbalanced, double-blind design, subjects consumed 400 ml of either CE or P 30 min prior to exercise, and 250 ml every 5 km thereafter during the run. Rectal temperature, heart rate, rating of perceived exertion, sweat rate, and respiratory exchange ratio were similar during the run for CE and P. Serum Na+, K+, Cl-, total protein, osmolality, blood lactate, urea nitrogen, and % change in plasma volume were also similar for both drink conditions; however, blood glucose was significantly higher (P less than 0.01) with CE. Running performance in the last 5 km was significantly faster (P less than 0.03) during CE (21.9 min) compared with P (24.4 min). Subjects reported no differences in stomach upset, bloating, or nausea between P and CE. Results indicate that CE replacement elicits similar thermoregulatory and physiological responses during prolonged running in the heat but increases run performance and blood glucose when compared with P. PMID- 1406181 TI - Validity of a cardiorespiratory fitness test for men with mental retardation. AB - The purpose of this study was to validate a field test of cardiorespiratory fitness for men with mental retardation. The subjects were 19 healthy young men (26 +/- 6 yr) with moderate mental retardation (IQ = 48 +/- 11). Each subject underwent a maximal treadmill test after a three-phase familiarization process. Each subject also completed a 1-mile walk test twice (Rockport Fitness Walking Test = RFWT). The correlation coefficients between peak VO2 on the treadmill and the two 1-mile walks varied from 0.78 to 0.83. When weight, height, age, heart rates of 1-mile walks, and their combinations were held constant, the correlations were strengthened. Using multiple correlation analysis the best equation for predicting peak VO2 was: Peak VO2 = 101.92 - 2.356(mile-1 time) - 0.42(weight). This model accounted for 85% of total variance. The standard error of estimate was 4.06 ml.kg-1.min-1. The test-retest reliability of the RFWT for the 19 subjects used in this study was very high (R = 0.97). This finding suggests that the RFWT is a valid and reliable field test for this population and appears to be a valid indicator of cardiorespiratory fitness for these men with mental retardation. PMID- 1406182 TI - A comparison between two forms of aerobic dance and treadmill running. AB - Aerobic dance has been reported to result in a disproportionately higher heart rate than running at a similar percent of VO2max. It has been suggested that the extensive use of the arms overhead during aerobic dance results in an increase in sympathetic outflow thereby disproportionately increasing the heart rate. To compare the hemodynamic and sympathetic nervous system activity responses during aerobic dance and treadmill running, nine healthy females exercised at approximately 50% of their VO2max during each of the following three exercise trials: aerobic dance where the arms were used extensively overhead (ABOVE), aerobic dance where the arms were kept below the shoulders (BELOW), and treadmill running (TR). Mean heart rate values during the ABOVE, BELOW, and TR trials were 136 beats.min-1 for all three trials. Mean VO2 values during the ABOVE, BELOW, and TR trials were 1.48, 1.51, and 1.47 l.min-1, respectively, and were not significantly different. Mean cardiac output for the ABOVE, BELOW, and TR trials were 13.5, 14.0, and 13.0 1. min-1, respectively, and were not significantly different. Postexercise blood lactate and norepinephrine values were not significantly different among the three trials. These results suggest a similar relationship between heart rate and VO2 during low intensity aerobic dance and running and do not support the contention that the use of the arms overhead during aerobic dance exercise elicits a disproportionately greater increase in heart rate as compared with running. Additionally these results demonstrate similar cardiovascular and sympathetic nervous system responses between aerobic dance exercise and running. PMID- 1406183 TI - Scientific basis of competitive cross-country skiing. AB - The sport of cross-country skiing had its origins as a utilitarian mode of travel more than 4000 yr ago. From hunters carrying weapons and moving about on carved wooden skis, the sport has evolved to spandex-clad competitors carrying reinforced fiberglass poles while gliding on high-tech composite skis. The widespread use of ski-skating techniques coupled with the technological innovations of the last decade have profoundly changed the nature of competitive cross-country skiing. This symposium is intended to summarize the current state of scientific knowledge about the sport. PMID- 1406184 TI - Mechanical constraints on Nordic ski performance. AB - Skiers, coaches, and sports scientists must work within mechanical constraints to improve performance. If Nordic skiing is to be improved by mechanical means, it will be achieved by affecting one or more of the major constraints: gravity, mass, friction, aerodynamic or hydrodynamic lift and drag, and centripetal force. For example, the skier who assumes a tucked position, drafts a competitor, and wears a drag-reducing hood and body suit is reducing aerodynamic constraints. Sliding friction may also be reduced by using specially prepared skis and by selecting skis appropriate for the snow characteristics of the race course. Skin friction hydrodynamic drag may also be affected by ski selection and by special base preparations. Gravity and mass constraints are diminished by using lightweight components, by carrying them in the least costly way, and by minimizing swing weight. The toppling effect of centripetal forces is addressed by leaning into turns. All of these examples address mechanical constraints in a way that reduces physical power requirements, and thus decrease the metabolic power required to ski at a given speed, as well as increasing the maximal speed attainable. PMID- 1406185 TI - Biomechanical analysis of cross-country skiing techniques. AB - The development of new techniques for cross-country skiing based on skating movements has stimulated biomechanical research aimed at understanding the various movement patterns, the forces driving the motions, and the mechanical factors affecting performance. Research methods have evolved from two-dimensional kinematic descriptions of classic ski techniques to three-dimensional analyses involving measurement of the forces and energy relations of skating. While numerous skiing projects have been completed, most have focused on either the diagonal stride or the V1 skating technique on uphill terrain. Current understanding of skiing mechanics is not sufficiently complete to adequately assess and optimize an individual skier's technique. PMID- 1406186 TI - Physiological comparisons of cross-country skiing techniques. AB - Since the popularization of ski skating, several investigations have compared the physiological responses of various cross-country skiing techniques. While this work is incomplete in fully characterizing the relative physiological demands of the different skiing techniques, some conclusions can be made. The diagonal stride technique is the least economical technique for skiing on flat ground. The magnitude of the difference in economy between the diagonal stride and skating techniques for skiing on flat terrain compares well with the 10-30% faster race velocities with the skating techniques. Nevertheless, it appears that the heart rates, blood lactate concentrations and perceived efforts elicited at a given oxygen uptake are similar between the diagonal stride and skating techniques. Therefore, the cardiorespiratory training benefits from classical skiing and ski skating should be similar if performed at the same heart rates or perceived efforts. Several studies have demonstrated that the double pole technique is the most economical cross-country skiing technique on flat terrain. Extended use of the double pole technique, however is probably limited by its greater anaerobic demands. PMID- 1406187 TI - Influence of body mass on cross-country ski racing performance. AB - The influence of body mass on cross-country skiing performance was evaluated by (i) a theoretical analysis of the relationship between body mass (M) and on one hand the maximal aerobic power and on the other the power expense of skiing, (ii) timing skiers in varied terrain during ski racing, (iii) comparing racing success between light and heavy skiers, and (iv) relating maximal aerobic power of skiers and power expense of skiing to body mass. The theoretical analysis indicated that the maximal aerobic power scaled with M2/3, while the mass exponent for the power expenses ranged from 1/3 to 1. The net result was that heavy skiers appear to be favored in all types of terrain but the steep uphills. During ski racing, heavy skiers displayed a tendency to be faster in all types of terrain, although no statistically significant effect was found. The racing success tended to be greater in heavy skiers among males but not among females. During skiing, maximal aerobic power and the power expense of skiing scaled with M0.7 and M0.4, respectively, indicating an advantage for the heavy skier. Altogether, these observations indicate that heavy skiers are favored, but also that other factors are more important than body mass for cross-country ski racing performance. PMID- 1406188 TI - Development of aerobic power in relation to age and training in cross-country skiers. AB - In most of the training studies on different populations the effects of training have been investigated up to a frequency of five to six times per week and a duration of 45 min per session. These correspond to the training regimens of 15 yr-old cross-country skiers and, consequently, the results cannot be applied to older athletes. The maximal oxygen uptake (VO2max) of cross-country skiers increases with age and training from about 55-60 to 75-80 ml.kg-1.min-1 between 15 and 25 yr of age. After 20 yr of age VO2max starts to level off, but elite skiers are able to increase VO2max further concomitantly with an increase in the volume of training and the volume of intensive training. The activity of oxidative enzymes in muscles of skiers is increased with training, but distance runners have had a higher oxidative capacity in their leg muscles. Although widely used by cross-country skiers, the training effects of roller skiing, skiwalking-skistriding, and long-distance training on skis are to a large extent unknown. However, intensive training at the intensity of "anaerobic threshold" or higher seems to be most effective in inducing improvements in maximal oxygen uptake; distance training at relatively low intensity seems to be most effective in producing improvements in the determinants of submaximal endurance. PMID- 1406189 TI - Technological advances in cross-country ski equipment. AB - Nordic skiing has a long history dating back to at least 2500 B.C. It is not surprising then that skiing equipment has undergone many changes. Today's skis, poles, and boots use the latest in space-age synthetics including carbon and Kevlar fibers, which has resulted in an unprecedented advance in ski equipment technology, producing ultralight yet strong equipment. These changes have played an important role in bringing about an improvement in racing performance with today's skiers being able to ski a course in half the amount of time that it would have taken just 60 yr ago. Estimates indicate the change in mass of racing equipment accounts for a relatively small amount (12%) of the improvement in race performance with changes in the functional characteristics of equipment, track preparation, and training practices being responsible for the remaining 88%. In addition to improvements in ski equipment, advances are being made in developing laboratory equipment used to assess an athlete's upper body power and endurance capacities. Lab testing with an arm ergometer showed its utility when it exposed a glaring deficiency in upper body power among a group of U.S. developmental skiers. Further improvement in ski equipment and lab testing tools are expected in the future as the worldwide technological revolution continues and Olympic Teams and sports science groups continue to work cooperatively. PMID- 1406190 TI - Factors affecting the oxygen cost of stepping on an electronic stepping ergometer. AB - The purposes of this study were to evaluate (a) the effects of step rate and upper body support on the VO2 and HR responses to fixed work rates on the StairMaster 4000 (SM), (b) the accuracy of the SM settings, and (c) how HR compared with that measured during grade-walking on a treadmill. Six subjects worked at a slow step rate for 6 min and then a faster step rate for the last 6 min of a 12-min test at SM settings of 4, 7, and 10 METs. Gas exchange and HR measurements were made at minutes 4-6 and 10-12. Variations in step rate had no effect on HR (P = 0.45) or VO2 (P = 0.84). The effect of using the arms and hands for support was studied using 6 subjects who worked for 12 min at 4, 7, and 10 METs; the first 6 min without support, and the second 6 min with support. Support resulted in lower HR (P = 0.017) and VO2 (P = 0.002) values at 10 METs. The measured MET values were about 20% lower than those specified by machine settings: True MET values = 0.556 + 0.745 (SM setting). Finally, at the same VO2, systematically higher (7-11 b.min-1) HR values were observed for the SM relative to the treadmill. PMID- 1406191 TI - The effect of trial size on statistical power. AB - Many research studies produce results that falsely support a null hypothesis due to a lack of statistical power. The purpose of this research was to demonstrate selected relationships between single subject (SS) and group analyses and the importance of data reliability (trial size) on results. A computer model was developed and used in conjunction with Monte Carlo procedures to study the effects of sample size (subjects and trials), within- and between-subject variability, and subject performance strategies on selected statistical evaluation procedures. The inherent advantages of the approach are control and replication. Selected results are presented in this paper. Group analyses on subjects using similar performance strategies identified 10, 5, and 3 trials for sample sizes of 5, 10, and 20, respectively, as necessary to achieve statistical power values greater than 90% for effect sizes equal to one standard deviation of the condition distribution. SS analyses produced results exhibiting considerably less power than the group results for corresponding trial sizes, indicating how much more difficult it is to detect significant differences using a SS design. These results should be of concern to all investigators especially when interpreting nonsignificant findings. PMID- 1406192 TI - Semi-pro football player who suffered a cerebral vascular accident following forced cervical flexion and subsequent spinal manipulation. PMID- 1406193 TI - Oxidation rate of four types of carbohydrates ingested 30 min before a period of prolonged exercise at moderate intensity in healthy male subjects. PMID- 1406194 TI - Stress fractures in young athletic women: case reports of unsuspected cortisol induced osteoporosis. AB - Stress fractures in the female athlete are common events, usually occurring in the lower limb and less often in the pelvic girdle. Two cases are presented of young women athletes who presented with initial lower limb stress fractures, but subsequently fractures of the pelvis and hip thought to be associated with their athletic activity. After careful medical evaluation, they were diagnosed with Cushing's syndrome. One patient had a microadenoma of the pituitary gland secreting excessive amounts of ACTH, and the other had a benign adenoma of the left adrenal gland. Both women had significant decreases in their spinal mineral density. After treatment, partial reversal of these spinal losses occurred. Although stress fractures in the female athlete might be common and thought to be associated with problems of amenorrhea, presentation of unusual anatomical sites for these fractures necessitates a more thorough evaluation for correctable secondary causes. PMID- 1406195 TI - Thigh compartment syndrome in a football athlete: a case report and review of the literature. AB - Although contusions of the thigh are common in all sports, a compartment syndrome from closed blunt trauma without a femur fracture is rare. Thigh compartment syndrome is unusual due to increased compliance of the thigh to accommodate increased expansion from hematoma or third space fluid. Compartment syndrome of the thigh is characterized by unrelenting pain, swelling, and limited knee range of motion. A single case of a thigh compartment syndrome caused by a direct blow to the anterior aspect of the thigh from a football helmet during kickoff occurred. Immediate thigh fasciotomy was performed. Early diagnosis with appropriate emergency treatment can avoid serious and permanent complications. PMID- 1406196 TI - Etiology of low back pain in elite boardsailors. AB - Seven elite boardsailors reporting nonradiating low back pain without leg pain during sailing volunteered for detailed examination. In these subjects, the onset of pain was limited to those occasions when sailing positions were held for a significant period of time, e.g., close hauled sailing or in light winds. No pain was described at any other time. The determination of possible antecedent factors was based on the results of clinical assessment, radiological evaluation, and computer tomography (CT) scanning. Apart from limited flexibility in some subjects, the clinical examination of these athletes was normal; CT changes in this group were limited to disc protrusions and bulges, and pars interarticularis defects. Despite the small number of subjects in the present report, it appears that the frequency of these problems exceeds that in the normal population. It may be possible to suggest that risk factors such as body position during prolonged sailing, particularly under light wind conditions without a harness, and limited flexibility may be associated with the radiological findings and may be implicated in the presence of low back pain, although further investigations appears warranted. PMID- 1406197 TI - Exercise capacity and breathing mechanics in patients with airflow limitation. AB - To investigate the impact of expiratory airflow limitation on ventilation during exercise, we studied six control subjects with normal lung function (FEV1/FVC = 79 +/- 6%) and eight patients with borderline-to-mild airflow limitation (FEV1/FVC = 68 +/- 4%) during cycle ergometry. VO2, HR, and VE/MVV were not different between the control subjects or patients during maximal or submaximal exercise. In contrast, five of the eight patients achieved maximal expiratory flow over a large portion (37%) of their tidal volume (VT) during submaximal exercise, whereas none of the control subjects achieved maximal expiratory flow. To estimate the fraction of expiratory capacity used by the control subjects and the patients, we calculated a mechanical ventilatory maximum (VEmaxCal) for each level of exercise using the individual's VT, end-expiratory lung volume (EELV), and maximal expiratory flow-volume curve. The patients used a greater fraction of their VEmaxCal at each level of submaximal exercise (P less than 0.03). Despite the flow limitation during submaximal exercise, EELV was similar between the control subjects and patients. In conclusion, even patients with borderline-to mild airflow limitation achieve maximal expiratory flow during submaximal exercise and these restrictions are not reflected by VE/MVV nor by EELV. PMID- 1406198 TI - Substrate utilization during treadmill running in prepubertal girls and women. AB - Ten prepubertal girls (9.1 yr) and 10 women (24.4 yr) were studied during 30-min runs at the same relative (70% VO2max) (RI) and absolute (7.2 km.h-1) (AI) intensities. Oxygen consumption and respiratory exchange ratio (RER) were monitored continuously during the exercise test. Venous blood samples were obtained before and immediately after exercise and were analyzed for glucose, lactate, FFA, and glycerol. During exercise at the same RI, RER was significantly (P less than 0.05) lower in the girls compared with the women. In addition, RER decreased significantly during exercise in the girls while the change did not reach significance in the women. Lactate concentration increased significantly during the exercise tests, this increase being greater in the women than in the girls during exercise at the same RI, but greater in the girls than in the women during exercise at the same AI. FFA and glycerol concentrations were significantly higher after the exercise tests in both groups. Glucose concentration did not change significantly during the tests in either group. Prepubertal girls rely more on fat utilization and less on carbohydrate metabolism than women during exercise of moderately heavy intensity. PMID- 1406199 TI - The effect of an anti-G suit on cardiovascular responses to exercise in persons with paraplegia. AB - The purpose of this study was to determine whether external pressure on legs and abdomen could prevent venous blood pooling in persons with paraplegia and thus positively affect their cardiovascular responses to arm exercise. To investigate this, five male subjects with paraplegia (P), with complete lesions between T6 and T12, and five male control subjects who were wheelchair bound (C) (due to a chronic lower extremity disability), performed submaximal arm-cranking exercise at 20%, 40%, and 60% of their maximal power output (Wmax), with and without an antigravity (anti-G) suit inflated to 52 mm Hg (1 psi). For P, higher preexercise systolic pressure (127 vs 117 mm Hg) was seen with the anti-G suit. At 40 and 60% Wmax, significantly lower heart rates (at 40% = 5.7%; at 60% = 10.6%) at similar cardiac outputs were seen for P with an anti-G suit. Although not significant, P also demonstrated higher stroke volumes at 40% (4.8%) and 60% (5.0%) Wmax with external pressure. For C, no differences in preexercise blood pressure or cardiovascular responses at all three exercise levels were seen with or without the anti-G suit. These data suggest that an inflated anti-G suit is able to prevent venous blood pooling and offers hemodynamic benefits in persons with paraplegia during submaximal arm-cranking exercise. In addition, this study reports a possible alternative to hosiery or functional neuromuscular stimulation that could be applied to all subjects with spinal cord injuries regardless of type or duration of the lesion or of muscle-atrophy. PMID- 1406200 TI - Aerobic fitness: I. Response of volume regulating hormones to head-down tilt. AB - We investigated the relationship of aerobic fitness to the response of volume regulating hormones to acute simulated microgravity. Six untrained (UT) and six endurance-trained (ET) healthy young males were studied in the head-down tilt (HDT) position of -6 degrees for 4 h. Peak oxygen uptake (VO2peak) and plasma volume (PV) were significantly greater in the ET (VO2peak = 61.7 +/- 1.6 ml.min 1.kg-1 and PV = 53.1 +/- 2.8 ml.kg-1) than in the UT (VO2peak = 38.4 +/- 1.7 ml.min-1.kg-1 and PV = 38.8 +/- 1.0 ml.kg-1). Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), norepinephrine (NE), renin activity (PRA), and aldosterone (PA) were measured prior to HDT and at minutes 2, 5, 15, 30, 60, 120, 180, and 240 during HDT. PRA and PA significantly decreased during the time of HDT in both groups. The changes in ANP and NE concentrations were not significantly different between the groups nor across time. However, in the ET subjects, the changes in PRA and NE were significantly correlated with the changes in ANP (r = 0.49, P less than 0.01; and r = 0.86, P less than 0.001, respectively); in the UT subjects, the changes in AVP, PRA, and PA were significantly associated with changes in NE (r = 0.34, P less than 0.03; and r = 0.59; and r = 0.53, P less than 0.01, respectively). PV significantly decreased during HDT, and was primarily related to the decrease in PA in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406201 TI - Aerobic fitness: II. Orthostasis and VO2peak following head-down tilt. AB - To determine whether endurance exercise trained (ET) subjects would experience greater reductions in peak oxygen delivery and orthostatic tolerance (OT) than untrained (UT) subjects, both peak oxygen uptake (VO2peak) during upright bicycle ergometry and tolerance time during 70 degrees head-up tilt (HUT) were compared within and between groups before and after 4 h of -6 degrees head-down tilt (HDT). Eight ET subjects with a mean VO2peak of 61.7 +/- 1.6 ml.kg-1.min-1 were matched for age, height, and weight with eight UT subjects (VO2peak = 38.4 +/- 1.7 ml.kg-1.min-1). Following HDT, decreases in plasma volume (PV) were larger for ET subjects (-3.7 +/- 0.5 ml.kg-1) than for UT subjects (-2.3 +/- 0.3 ml.kg 1), P less than 0.03. Reductions in VO2peak for ET subjects (-5.4 +/- 1.1 ml.kg 1.min-1) were also greater than for UT subjects (-2.4 +/- 0.8 ml.kg-1.min-1), P less than 0.05. The ET (N = 6) subjects also had a significant decrease in OT time (-13.0 +/- 4.2 min) during post-HDT HUT, which was not observed for the UT group (N = 6). A significant inverse correlation was found pre-HDT VO2peak and the change in OT time, r = -0.74, P less than 0.01. The decrease in OT was also significantly correlated to the PV decrease, r = 0.59, P less than 0.04. The UT subjects had significantly augmented pressor responses to HUT manifested by the increases in both HR and MAP following HDT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406202 TI - Energy metabolism and fuel utilization. AB - 1) Total energy expenditure during marathon training and competition is among the highest reported for any endurance activity. 2) Although training intensity for the marathon may vary between 60-125% of maximal physical working capacity, elite runners must run consistently at about 80-90% of VO2max in order to achieve successful competitive performances. 3) Earlier studies demonstrated that carbohydrate was the preferential fuel for endurance exercise, but more recent studies have suggested a greater role for lipids than previously thought. Also, proteins may contribute as much as 5-10% of the total energy to a marathon performance. 4) The preponderance of Type I and IIA skeletal muscle fibers among marathon runners and their significantly improved storage capacity for intramuscular lipids and increased mitochondrial density may account for increased reliance on oxidation of fats. PMID- 1406203 TI - Sports anemia, iron supplements, and blood doping. AB - 1) Athletes tend to have lower hemoglobin concentrations than sedentary counterparts. This has been called sports anemia, a misnomer. 2) Sports anemia is a false anemia and a beneficial adaptation to aerobic exercise, caused by an expanded plasma volume that dilutes red blood cells. 3) Athletes, however, can also develop true anemia, most commonly caused by iron deficiency. True anemia curbs athletic performance, but nonanemic iron deficiency does not. 4) Iron supplements are useful for women endurance athletes who repeatedly develop iron deficiency anemia despite dietary advice. 5) Some endurance athletes today are blood doping by abusing recombinant human erythropoietin (rEPO). They risk dying to win. PMID- 1406204 TI - Nutrition for the marathon and other endurance sports: environmental stress and dehydration. AB - 1) During exercise, the body's ability to safely regulate internal temperature is influenced by the environment, exercise intensity, clothing, and the athlete's level of fitness and acclimation. 2) Effective thermoregulation during exercise in the heat requires the evaporation of sweat. The onset of sweating during exercise is triggered by an increase in core body temperature. 3) Dehydration compromises cardiovascular and thermoregulatory function, limits physical work capacity, and increases the risk of heat-related health problems. 4) Physiological and behavioral adaptations help the body cope with the combined demands imposed by exercise and environment. 5) Ad libitum fluid intake is insufficient to protect against dehydration. PMID- 1406205 TI - Benefits of fluid replacement with carbohydrate during exercise. AB - Ingestion of approximately 30-60 g of carbohydrate during each hour of exercise will generally be sufficient to maintain blood glucose oxidation late in exercise and delay fatigue. Since the average rates of gastric emptying and intestinal absorption exceed 1,250 ml.h-1 for water and solutions containing up to 8% carbohydrate, exercising people can be supplemented with both carbohydrate and fluids at relatively high rates. When cyclists exercise at competitive intensities for 2 h in the heat with a sweat rate of 1,400 ml.h-1, it is clear that the closer that fluid consumption matches sweating rate (at least up to 80% of sweating rate), the better. Increasing dehydration, due to inadequate fluid consumption, directly impairs stroke volume, cardiac output, and skin blood flow, which results in larger increases in body core temperature, heart rate, and ratings of the difficulty of exercise. This same phenomenon probably also applies to running, which argues against the notion that a certain amount of dehydration (i.e., up to 3%) is permissible and without major cardiovascular consequences. However, runners generally drink only 500 ml.h-1 of fluid and thus allow themselves to dehydrate at rates of 500-1,000 ml.h-1. The performance question boils down to "Will the time lost as a result of drinking larger volumes be compensated by the physiological benefits drinking produces and the faster running pace that might be achieved during the last half of the race?" However, if the goal is safety, which means minimizing hyperthermia, there is no question that the closer that the rate of drinking can match the rate of dehydration, the better. PMID- 1406206 TI - Nutritional manipulations before and during endurance exercise: effects on performance. AB - 1) Ingesting CHO during prolonged, moderate-intensity (60-85% VO2max) exercise can improve performance by maintaining plasma glucose availability and oxidation during the later stages of exercise. 2) Plasma glucose may be oxidized at rates in excess of 1 g.min-1 late in exercise. Athletes therefore need to ingest sufficient quantities of CHO in order to meet this demand. This can be accomplished by ingesting CHO at 40-75 g.h-1 throughout exercise or by ingesting approximately 200 g of CHO late in exercise. Ingesting CHO after fatigue has already occurred, however, is generally ineffective in restoring and maintaining plasma glucose availability, CHO oxidation, and/or exercise tolerance. 3) No apparent differences exist between glucose, sucrose, or maltodextrins in their ability to improve performance. Ingesting fructose during exercise, however, does not improve performance and may cause gastrointestinal distress. 4) The form of CHO (i.e., solid vs liquid) ingested during exercise is unlikely to be important provided that sufficient water is also consumed when ingesting CHO in solid form. 5) Ingesting 50-200 g of CHO 30-60 min before exercise results in transient hypoglycemia early in exercise, but this does not affect the rate of muscle glycogen utilization or, in most people, cause overt symptoms of neuroglucopenia. Whether performance is impaired, unaffected, or enhanced by such pre-exercise CHO feedings remains equivocal. 6) Ingesting 200-350 g of CHO 3-6 h before exercise appears to improve performance, possibly by maximizing muscle and/or liver glycogen stores or by supplying CHO from the small intestine during exercise itself.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406207 TI - Recovery from endurance exercise. AB - 1) During training for and competition in endurance exercise athletes often significantly reduce both liver and muscle glycogen reserves. 2) Replenishment of muscle glycogen probably occurs preferentially over the replenishment of liver glycogen after exercise. 3) Muscle and liver glycogen can be replenished within 24 h after exercise provided adequate carbohydrate is consumed. 4) To replenish muscle glycogen within 24 h, 8-10 g carbohydrate.kg-1 body weight should be consumed. 5) To optimize muscle glycogen synthesis during the 4-6 h after exercise, carbohydrate must be consumed immediately after exercise and at frequent intervals thereafter. 6) While normal muscle and/or liver glycogen levels can be normalized 24 h after exercise, muscle function may or may not be fully recovered. PMID- 1406209 TI - Food selection for endurance sports. AB - 1) The body requires at least 40 nutrients that are classified into six groups: protein, carbohydrate, fat, vitamin, mineral, and water. These nutrients cannot be made in the body and so they must be supplied from solid or liquid foods. 2) Fat, carbohydrate, and protein contain energy that is measured in units called kilocalories. Alcohol also contains kilocalories, but is not a recommended energy source for endurance exercise. 3) Foods in endurance sports training programs should provide adequate fluids to prevent dehydration; energy intake that is high in carbohydrate, low in fat, adequate in protein, and that maintains desirable body weight and desirable proportions of fat and lean weight; and sufficient amounts of vitamins and minerals. 4) Six categories of food types form the fundamentals of good diets for endurance exercise training and include: fruits, vegetables, grains-legumes, lean meats, low-fat milk products, and fats-sweets. Vegetarian diets include all food type categories except meat and/or milk products. 5) Fat and carbohydrate content of foods in each food type category varies greatly because of how foods are prepared. 6) The Food Pyramid and Sports Food Swap are guides for selecting foods that provide recommended amounts of essential nutrients for endurance exercise. 7) Before, during, and after endurance exercise, food intake should include adequate amounts of easily digestible, high carbohydrate foods that are familiar and psychologically satisfying. 8) Easily digestible high carbohydrate liquid or solid foods should be eaten soon after exercise is stopped to maximize rates of glycogen replacement. 9) Dehydration can be prevented by adequate fluid intake before, during, and after exercise. 10) Any food plan should be tested before a competition to find out how well that plan works for an athlete. PMID- 1406208 TI - Training for endurance sport. AB - 1) An endurance athlete's performance level is determined largely by three physiological variables: maximal aerobic power, lactate threshold, and economy. Training strategies should be directed toward improvement of these factors. 2) Successful endurance training programs typically include an individually constructed combination of three major training strategies. These are long duration, moderate intensity training; moderate duration, high intensity training; and short duration, very high intensity training. 3) Endurance training involves a large daily expenditure of energy, and much of this energy is derived from catabolism of carbohydrates. Accordingly, it is essential that the endurance athlete's diet be rich in complex carbohydrates and provide the total amount of energy needed to maintain energy balance. PMID- 1406210 TI - Prevention and treatment of injuries to runners. AB - 1) Many otherwise healthy runners are prevented from participating fully in their chosen endurance sport because of overuse injuries. 2) The most important risk factor for incurring an overuse injury is a training error, such as excessive mileage, sudden change in training distance or intensity, too much hard interval training, improper footwear, and running on chambered surfaces. 3) Although the knee is the most frequent site of injury in runners, any part of the lower extremity may be affected. 4) Tendinitis, muscle strain, and stress fractures are the most common overuse injuries in endurance athletes. 5) Prevention of injury through elimination of risk factors is clearly preferable to treatment. If injury does occur, treatment should include appropriate medical care, athlete education, cross-training, specific rehabilitative exercises, and a programmed return to running. PMID- 1406211 TI - [Retrospective study of infection by the human immunodeficiency virus in pregnant women. Future of the child and the mother]. AB - 5.4% (108 of 2,000) women have been confirmed for HIV 1 infection in Brazzaville in 1987. 1,172 deliveries have been registered by study, 7.76% have been occurred in HIV+ women. The prevalence of miscarriages was significantly, higher in HIV+ women than in HIV- ones (p less than 0.001). The birth-weight of new-borns was not significantly different among the children born to HIV+ and HIV- mothers. There were the various probable reasons of death of children born to HIV+ mothers. More frequently the respiratory affections with persistent hyperthermia were noticed. During the follow-up, in all groups of age, the fever with failure of thrive were the most frequent signs (50%) with pneumopathy. The clinical picture was completed by diarrhoea after six months of live. PMID- 1406212 TI - [Endocrinological aspects of acquired immunodeficiency syndrome (AIDS)]. AB - The acquired immunodeficiency syndrome (AIDS) is a severe disease. Lung, brain and digestive complaints that result in opportunistic infections and neoplasms are the most documented. The endocrine disorders, the description of which is recent on the basis of post-mortem data, motivated some authors to undertake studies in order to evaluate endocrine function in patients infected with human immunodeficiency virus (HIV). An increase in serum cortisol level due to stress adaptation in the early stage of the disease is reported, whereas peripheral adrenal insufficiency, although unusual, appears in the late stage. Hypogonadism is common in men with HIV infection but its origin is discussed, central or peripheral. The thyroid function is generally preserved, but low T3 syndrome which correlates with bad prognosis may be observed. Anterior hypopituitarism, which is rare, hyponatremia more frequent because of its etiopathogenic factors in AIDS, constant and precocious hyperprolactinemia, are noticed. The episodes of asymptomatic or severe hypoglycemia may be explained by inanition and side effects of drugs. The non-specificity of the clinical manifestations of endocrine dysfunction masked by the classic signs of AIDS, shouldn't make forget the systematic search of glandular abnormalities as soon as an evocative symptomatology is conspicuous. The mechanisms of endocrine complications are badly known, but opportunistic infections, drugs, particularities related to the structure of HIV and interleukin 1 (IL1) surely play a role. The recognition of endocrine disorders is essential for optimal therapy because, unknown, their evolution is dramatic. PMID- 1406213 TI - [Glomerulopathies in schistosomiasis. Current data]. AB - The authors studied various glomerular injuries in schistosomiasis. They occurred more after with Schistosoma mansoni and rarely with other Schistosoma species. Different lesions were observed: the membrano-proliferative type is frequently noted; but mesangial and extramembranous glomerulitis were also described. The pathology of glomerular lesions is Immune mediated with activation of complement patway and deposit of immune circulating complexes. PMID- 1406214 TI - [Preliminary data on dermatomycoses in Ouagadougou (Burkina Faso)]. AB - This study is a contribution to a best knowledge of mycosis in Burkina Faso where the data concerning these diseases are very old. It has been focused on the clinical and mycological features of the dermoskeloton mycosis through the consultations at the two offices of dermatology in the city of Ouagadougou. From April to October, 1990, 216 patients have been taken census of, and they have shown 265 lesions among which 143 mycosis of the skinfolds (54 p. cent), 45 onychomycosis (17 p. cent), 29 palmoplantar mycosis (11 p. cent), 24 mycosis of the glabrous skin (9 p. cent) and 24 mycosis of the scalp (9 p. cent). From these 265 lesions we have isolated 156 strains of dermatophytes and 108 strains of candida. The species which have been seen more frequently are Candida albicans (30 p. cent), Trichophyton rubrum (19 p. cent), Trichophyton soudanense (13 p. cent) and Trichophyton tonsurans (8 p. cent). This study has enabled the identification of some clinical features and some responsible agents of the dermatoskeloton mycosis in Ouagadougou. It will lay the foundation for further specific studies in the country. PMID- 1406215 TI - [Congenital malaria]. AB - Several physiopathological hypothesis may explain the frequent transmission of malaria from a pregnant woman to the foetus, and its obstetrical consequences. Because of immunological reasons, such a transmission is most often silent, but some severe forms of congenital malaria do exist and they justify the chemoprophylaxy for pregnant women, and the treatment of any presumptive attack of malaria during pregnancy. PMID- 1406216 TI - [Simultaneous association of tubercular meningitis and cryptococcal meningitis in an African with human immunodeficiency virus HIV positive serology. University Hospital Center of Bujumbura,Burundi]. AB - The authors report a connection between a meningitis tuberculosis and a meningoencephalitis with cryptococcus in the case of an african VIH+. The diagnostic of a meningitis tuberculosis was retained on an indirect arguments, this of meningoencephalitis of direct arguments (antigen cryptococcus, cultivation on Sabouraud environment). The pulmonary tuberculosis and/or extrapulmonary tuberculosis is current in Central Africa during HIV infection, as well as the crytococcosis during AIDS. But, any observation on neuromeningitis strike of those two infections have been reported up to now. PMID- 1406217 TI - [Ascariasis of the cervix]. AB - The authors report a case of ascaris lumbricoides located in the cervix uterus of a patient suffering from gonococcal salpingitis. Reviewing the literature, they conclude that the most likely way to the parts genitals was a transanal migration toward vagina. PMID- 1406218 TI - [Cardiac manifestations of sickle cell disease]. AB - In this study the authors report the cardiac complications seen in the course of sickle-cell disease. Among 41 homozygot patients the complications reported were as follow. Effort dyspnea in 15/32 (46% cases); systolic souffle in 36 patients (87.8% of cases); cardiomegaly in 30 patients (17% of cases) and electric abnormalities in 70% of cases. The echotomography practised in 27 cases was normal in 12 cases and showed a hyperkinetic aspect in 10 cases, a cardiomyopathy in four cases. PMID- 1406220 TI - Microsurgery. PMID- 1406219 TI - [Peripheral and bone marrow hematological modifications in infection by the human immunodeficiency virus (HIV) in central Africa. Diagnostic and prognostic significance]. AB - From the 24 March 1988 to the 15 June 1989, we noticed the peripheric and medullar haematologic modifications of 46 patients infected by HIV, classified in the group IV of CDC. The haematologic modifications found are: a peripheric cytopenia with a constant anemia often serious, a leuconeutropenia, a mild or missing lymphopenia. In comparison: the bone marrow is often rich in the different lineage with more often a sharp lymphoplasmocytal reaction, sometime very characteristic on the cytological side. 2 myeloid leukemia were diagnosed by participation of the myelogram. At least, the proteinogram showed a major polyclonal hypergammaglobulinemy sometimes monoclonal. PMID- 1406221 TI - Vascularized fibular graft for reconstruction after resection of aggressive benign and malignant bone tumors. AB - From 1982 to 1991, 19 patients at Nara Medical University, Kashihara, Japan, underwent resection of aggressive benign and malignant bone tumors, with limb salvage and reconstruction by free vascularized fibula grafts. The patients were followed up for an average of 54 months. The reconstructed site was the jaw in 6 cases, upper extremity in 3, spine in 1, pelvis in 2, and lower extremity in 7. Six patients had aggressive benign lesions, and 13 had malignant lesions. The sizes of the resultant bone defect ranged from 6 to 20 cm, and the lengths of fibular used ranged from 8 to 24 cm. The average time to union was 4.1 months (2 9 months) in the extremities and pelvis. Local recurrence was observed in 3 cases, for whom vascularized fibula grafts were performed for recurrent tumors. In cases of primary untreated tumors, no recurrences occurred. Therefore, this procedure should be performed at the time of primary operation after extensive resection of an aggressive benign or malignant bone tumor. PMID- 1406222 TI - Vein grafts in reconstructive microsurgery of the lower extremity. AB - This paper describes surgical techniques and results of lower extremity microsurgical reconstruction using vein grafts. During a 5 year period, free tissue transfers were used to reconstruct 118 lower extremity defects in 109 patients. In 28 of these cases (24%), saphenous vein grafts were used when reconstruction would otherwise have been difficult or impossible. A preliminary arteriovenous fistula was established between the proximal arterial source and the final venous drainage in the majority (26) of cases. Venous drainage was left intact at the point of entry into the deep venous system in 23 cases. Three complications included anastomotic clotting in 2 patients and postoperative blow out of the vein graft in another; all were treated without flap loss. Flap survival was 86% in vein grafted patients and 94% in those cases in which vein grafts were not used. Flap loss was related in each case to the nature of the pre existing condition, rather than to vein grafting per se. PMID- 1406223 TI - Short- and long-term evaluation of arteriovenous fistulas for chronic hemodialysis. AB - One hundred ninety-three internal arteriovenous (A-V) fistulas were performed on patients with renal failure in the last eleven years. The A-V fistulas were divided on the basis of the following: side-to-side between the radial artery and cephalic vein (157 cases); end-to-side between the cephalic vein and radial artery (11 cases); end-to-end between the radial artery and cephalic vein (5 cases); A-V fistulas between the brachial artery and the cephalic, basilic or medial cubital vein (20 cases). The side-to-side A-V fistulas achieved an immediate patency in 88% of cases, lower than each of the other groups. However, the subsequent long-term failure rate was less than the other groups. In addition, satisfactory function was maintained at a high level (93%) during the follow-up period. The end-to-side and end-to-end A-V fistulas showed higher percentages of immediate patency (90% and 100%, respectively), although they were used more often on patients with vascular problems. Diabetic nephropathy was the main factor associated with thrombosis of A-V fistulas. PMID- 1406224 TI - Hair growth following scalp microvascular flap transfer for baldness due to burn injury. AB - A female patient, 8 years of age, presented with baldness of the right scalp following deep scalds from boiling soup landing on the head, neck, and chest. The depth of the burn was severe enough to cause baldness. She was primarily advised to wear a wig to address the problem of baldness on one side. Surgery was planned to use uninjured scalp skin to offer hairy skin coverage of the bald site. A left scalp skin flap (2.5 by 7 cm) based on the superficial temporal artery and vein was transferred to the bald area, with microvascular anastomosis to the superficial temporal vessels on the right side. There was complete survival of the flap with uneventful recovery and satisfactory growth of hair. Hair growth from the flap was comparatively thicker than from the rest of the scalp. This microvascular flap has produced sufficient hair to cover the entire area of the baldness and the patient does not need to wear a wig. PMID- 1406226 TI - Microsurgical repair of the parotid duct. AB - Because of its relatively small caliber lumen, traumatic injuries of the parotid duct appropriately lend themselves to microsurgical repair. With the evolution of more modern techniques and materials, inert nylon microsutures placed under magnification permit an ideal atraumatic anastomosis of the divided ends of the parotid duct. Such an exact approach may also obviate the need for long-term stenting across the site of repair, which remains a controversial issue. PMID- 1406225 TI - Neck resurfacing with free tram flap. AB - Anterior neck defects are best reconstructed with flaps, to avoid contractures and extensive scarring. Local or distal flaps are hampered by significant donor site disability. The development of the TRAM flap for breast reconstruction has improved our armamentarium in reconstructive surgery. This paper purports to demonstrate the superiority of the free bilateral TRAM flap applied for anterior neck resurfacing. Two cases with such anterior neck conditions are presented. PMID- 1406227 TI - Successful replantation of digits and restoration of partial hand function: a case report. AB - A case of a five-finger amputation and avulsion injury with salvage of two digits combined with island flap coverage of the remaining skin defect is reported. The salvaged digits were replanted onto the ulnar and radial borders of the hand stump and rotated to oppose one another. Recovery of partial hand function is reported. PMID- 1406228 TI - Vascularization of skin following implantation of an arteriovenous pedicle: implications in flap prefabrication. AB - In a rat model, a skin flap was fabricated by implantation of a distally ligated arteriovenous pedicle. The femoral artery and vein were implanted as a unit beneath the abdominal skin, a portion of which was later raised as an island flap, based on these vessels. Percentage area of survival, tissue blood flow, and pattern of vascularity were compared in two groups of flaps. In group I, the pedicle to be implanted was dissected with a cuff of surrounding muscle still attached; in group II, the pedicle was skeletonized to the level of adventitia. Flap survival in the two groups was similar (73% vs. 77%), as was skin blood flow (5.4 vs. 5.7 ml/100 g/min). Angiography demonstrated two principal patterns of vascularization: connection between donor and recipient vessels (inoculation), and sprouting and arborization of new vessels. Strengths and limitations of this and other models of flap "prefabrication" are discussed. PMID- 1406229 TI - Further investigation of secondary venous obstruction. AB - The first ischemic insult a tissue suffers is primary (1 degree). A second ischemic episode, such as thrombosis after free tissue transfer may be regarded as secondary (2 degrees) ischemia. The current study investigated 2 degrees ischemia in rodent epigastric flaps. Flaps were elevated in 50 Sprague-Dawley rats: group 1 had 5 hours 1 degree venous ischemia induced by placement of microvascular clamps; group 2 was like group 1, except venous continuity was re established by venous anastomosis after resection of the venous segment previously microclamped; group 3 had 15 minutes of 1 degree ischemia, 24 hr later 5 hr of 2 degrees venous ischemia was induced by placement of microvascular clamps; group 4 was like group 3, except the venous segment was excised. Necrosis was evaluated on postoperative day 7. Both secondary ischemic groups had significantly less flap survival than the corresponding primary ischemic groups (P less than 0.001 for both). Resection of a portion of the vein and subsequent microanastomosis did not reduce flap survival (NS). Secondary venous ischemia of 5-hr duration is poorly tolerated by rodent skin flaps. There was no difference in flap survival in those flaps whose veins were clamped for 5 hr compared to those flaps whose clamped venous segments were resected and re-anastomosed. PMID- 1406230 TI - Carotid blood flow in anesthetized rats: effects of carotid ligation and anastomosis. AB - An experimental model was developed for continuous measurement of the common carotid blood flow, in the anesthetized rat, with an electromagnetic flowmeter. The mean carotid blood flow for 41 rats averaged 3.2 +/- 0.2 ml/min at an average mean arterial pressure of 101 +/- 2.5 mm Hg and arterial pO2 of 106 +/- 3.4 mm Hg, pCO2 of 38 +/- 1.2 mm Hg, and pH of 7.36 +/- 0.02. This model allowed short- and long-term carotid hemodynamic changes to be recorded after contralateral carotid ligation or end-to-side carotid anastomosis. After ligation of the contralateral carotid, blood flow through the intact carotid increased 25% (at about 1 week) and 45% (at about 5-6 months), whereas, after anastomosis, carotid blood flow increased 76% and 89% at periods comparable to those after ligation. Arterial pressure and gases did not change throughout the experimental periods. Probable mechanisms involved in these carotid hemodynamic changes are discussed. PMID- 1406231 TI - Vascularized and nonvascularized parathyroid gland transfer: a comparative study. AB - There is currently no animal model available to study the results of vascularized parathyroid gland autotransfers and nonvascularized autotransfers in the same model. This study was undertaken to determine the technical feasibility of performing microvascular parathyroid gland autotransfers in the dog, and to compare the postoperative levels of calcium, phosphorous, and parathyroid hormone (PTH) levels to a group of dogs who underwent nonvascularized parathyroid gland transfers. Dogs in the nonvascularized group were unable to maintain normal calcium without supplements, whereas dogs in the vascularized group maintained levels in the normal range. Microsurgical techniques allow transplant of a precise amount of parathyroid gland with its vascular supply to another part of the body with almost immediate restoration of function. PMID- 1406232 TI - Microsurgical use of polydioxanone (PDS) suture: an experimental report. AB - Although many technological advances have been made in surgical materials, nylon is still the main suture material use for microvascular surgery. This study sought to evaluate polydioxanone (PDS) sutures for use in microvascular anastomoses. Twenty-eight male Sprague-Dawley rats were used in this experiment. Spatula-type needles with 9-0 PDS suture were used to anastomose the right femoral arteries, with 9-0 nylon used on the left side. The arteries were observed for 1, 2, 3, 4, 8, 12, and 16 weeks after surgery to determine arterial patency and to evaluate vascular pathology. Results were comparable between PDS and nylon. We suggest that if the suture material is redesigned to allow smooth passage through the tissue, and if the needle used in conjunction with the suture is improved, PDS may offer an excellent material for microvascular anastomosis. PMID- 1406233 TI - Chronic cyclosporin A therapy in rats. AB - We investigated the pharmacokinetics of cyclosporin A (CsA) blood levels and drug toxicity in a chronic rat study in which long-term (30 weeks) CsA was administered. Ninety Lewis rats received subcutaneous CsA at 5 mg/kg/day for 12 weeks, at which time CsA injections were stopped in 50 animals. The remaining 40 rats were maintained on 5 mg/kg CsA daily until week 18 and then switched to an alternate day dosing until week 30. All rats were observed daily and weighed weekly. Whole blood CsA levels were determined by a commercially available radioimmunoassay kit. The daily dosing regimen resulted in greatly elevated trough CsA levels (greater than 1,600 micrograms/liter) and substantial chronic systemic toxicity, with weight loss and death in eight animals. Alternate day dosing reduced trough levels (mean 1,311 micrograms/liter) and decreased toxicity. Chronic administration by the subcutaneous route resulted in a considerable depot effect, with constancy of drug levels over a 48 hr dosing interval and a slow decline of drug levels (15 days) upon cessation of treatment. These results underscore the importance of monitoring both body weight and blood CsA levels in rodent studies when CsA is employed. Investigators should be aware of drug accumulation with chronic therapy and the consequent need to modify dosing to prevent toxicity. PMID- 1406234 TI - Endothelialization of microporous polytetrafluoroethylene grafts in the infrarenal aorta and caval vein of the rat. AB - To study healing and endothelialization of vascular grafts, microporous polytetrafluoroethylene (PTFE) prostheses 2 mm in inner diameter and 5 mm long were implanted into the infrarenal aorta or caval vein of the rat. Patency was assessed in six rats from each group at days 3, 7, 14, 28, and 56 after implantation. Four grafts were occluded, two in the aorta (56 days) and two in the caval vein (3 and 14 days). The prostheses were examined via scanning electron and light microscopy for evaluation of endothelialization. At 3 days, the inner surface of the aortic grafts was covered by a plasma proteinaceous layer and that of the caval vein grafts by a thin mural thrombus. Endothelial cells then migrated from aorta/caval vein edges over the graft. At 14 days, the caval vein grafts were completely re-endothelialized, and, at 28 days, the mural thrombus in these grafts was replaced by neointima. In contrast, endothelialization of the aortic grafts had advanced only 1 mm at about 56 days, never forming a complete endothelial layer. We conclude that endothelialization of microporous PTFE prostheses is more rapid and complete in the caval vein than in the aorta of the rat. PMID- 1406235 TI - Experimental study of free toe replantation in rats. AB - A rat model for free second toe replantation, free hallux-to-thumb transplantation, and combined free hallux-to-thumb transplantation and free second-toe-to-index transfer is described. Experimental devices, operative methods, and the keys to success are discussed. PMID- 1406236 TI - Skeletal fixation in the rabbit knee transplantation model. AB - The immature rabbit knee model for epiphyseal plate transplantations has been used by a number of investigators. Rigid fixation of the femoral osteosynthesis has been difficult to achieve reliably. This paper describes a new technique for obtaining consistent and satisfactory skeletal fixation in this model. The tibia was internally fixed with an ASIF/AO four-hole minifragment plate. The femur was fixed with a 2.4 mm Steinman pin supplemented with two 26 gauge stainless steel interosseous wire loops placed at right angles to each other. PMID- 1406237 TI - [Toxicological basis for evaluating health risk]. AB - The fundamental premises and toxicological methods used to evaluate exposure to chemicals in the environment have been discussed, with particular regard to the approach and methods for health risk assessment of carcinogens and non carcinogens. The main disputable problems related to risk assessment and risk estimation have been listed. PMID- 1406238 TI - [Protein fractions in workers exposed to organic solvents]. AB - Industrial workers exposed to organic solvents were subject to examinations consisting in the assessment of the composition of serum proteins. The analysis revealed frequent shifts in protein fraction pattern. It was noted that the increased concentrations of organic solvents metabolites in urine have been usually accompanied by the increased gamma-globulins levels with a simultaneous decrease in albumin fraction and plasmatic index. PMID- 1406239 TI - [Does formaldehyde-induced asthma exist?]. AB - Formaldehyde is a ubiquitous airborne pollutant in our modern environment. There are many potential sources of formaldehyde in the industrial setting. Ambient formaldehyde affects primarily the upper airways and eyes. Lower airway and pulmonary effects occur at exposure levels between 6-38 mg/m3. It is so soluble and rapidly metabolized that it seldom reaches the lower respiratory tract to inflict damage. There is no consistent evidence indicating that formaldehyde can be a respiratory sensitizer. It may, on rare occasions, induce bronchial asthma at relatively high exposure doses. There are no conclusive studies that would prove the development of de novo-IgE-mediated respiratory tract symptoms as resulting from inhalation of formaldehyde. PMID- 1406240 TI - [Local-action vibration and mechanical stress--their hygienic characteristics and medical evaluation of exposed workers]. AB - Medical examination and assessment of the hand-transmitted vibration and mechanical shocks were performed in 69 workers using chipping hammers, grinding tools, pneumatic hammers and forge hammers. Out of the 15 chippers examined, 5 presented vibration-induced white finger syndrome. The latency period for the syndrome was found to be similar to that predicted in the ISO guidelines no. 5349. Twenty seven hammer-using operators complained of joints pain within the upper extremities. The results of the examinations indicate that the work under conditions of mechanical shocks may increase the risk of vibration-induced pathology. PMID- 1406241 TI - [Principles of medical expert testimony regarding adolescents' capacity for practical vocational training and work]. AB - The presented approach to adolescents' vocational guidance is based on the ILO principle that work should conform to psychophysical conditions of the worker which should be evaluated before the beginning of work. In the paper the main health problems influencing the work capability have been discussed. It is suggested that the student, his parents and tutor should be informed about his health impairments, the degree of disability and therapeutic possibilities. The psychophysical features characteristic of the adolescence justify the health protection against occupational exposure to harmful agents as well as the activities, for health education and health promotion at school. PMID- 1406242 TI - [Biological testing of the fibrogenic effect of dust from the "Sosnowiec" mine on the lung tissue]. AB - In order to determine biological aggressiveness of settled dusts (mechanical, crumbled) and dusts collected using the gravimetric method, experimental studies were carried out, including: 1) evaluation of the physicochemical parameters (size of dust particles, content of silica, metals and other chemical compounds), 2) evaluation of the haemolytic activity, 3) experimental evaluation of fibrogenic potentials by means of: a) intraperitoneal test--to identity morphological type of reactive changes in the peritoneum and b) intratracheal test--to determine the level of hydroxyproline (collagen) in lungs and the morphological type of reactive changes. Albino rats were used for the experiment. The animals were divided into ten groups which received a single intratracheal injection of 50 mg of mining dust in 0.9% NaCl suspension. Comparative evaluation of biological aggressiveness of mining dusts was conducted basing on the findings of collagen levels in lungs. After the end of the experimental period (3 and 6 months, respectively) histopathological a examination of the lungs and mediastinal lymph nodes was made and the collagen levels in the pulmonary tissue (following Stegemann) were determined. As evidenced by the results of the pathomorphological examination and a statistical analysis: 1) after intratracheal injection the mining dusts induced changes within the respiratory system e.g. inflammatory process and emphysema. The exposure also brought about double increase of collagen level as compared to the control group, 2) histopathological study of the lungs and lymph nodes did not reveal progressive development of fibrogenic changes, 3) cytotoxic test showed differences in the haemolytic activity of settled dust and dusts collected by the gravimetric method. PMID- 1406243 TI - [Comparative evaluation of the effects of detergents Emulkop and Rokafenol N-8 on the aggressiveness of coal mine dust in the aspect of prevention of its biological effect]. AB - Comparative studies on the impact of the detergents Emulkop and Rokafenol N-8 upon the development and course of experimental pneumoconiosis caused by mine dusts were carried out. Albino rats and rabbits were used for the experiment. Methodological assumptions were based on the analogy with the conditions observed at the workplaces where some means of dust control were used. The acute toxicity evaluation was based on determination of the medial lethal dose (DL50) after intragastric administration of the detergents. Irritating action of the detergents on the skin was also evaluated. The effect of the detergents on the aggressiveness of selected dusts was estimated by means of the intratracheal and intraperitoneal tests. At the end of the experimental period (3 and 6 months, respectively) histopathological investigations of the lungs and mediastinal lymph nodes were carried out, and the hydroxyproline (collagen) levels in the pulmonary tissue were determined. According to Hodge and Sterner Chemical Substance Toxicity Classifications, Emulkop has been classified as non-toxic, and Rokafenol N-8 as a weakly toxic substance. On the basis of the investigation results obtained it has been established that: 1) Rokafenol N-8 does not qualify for use in coal mines as a formulation designed for dust control because it doesn't eliminate coniotic changes and causes a significant increase in the level of hydroxyproline (collagen) in pulmonary tissue, 2) in the case of Emulkop our studies have shown that this detergent can be used to prevent pneumoconiosis in coal mine workers. PMID- 1406244 TI - [Serpentine mine "Naslawice" as the source of contamination of soil and agricultural plants with metals and fibrous minerals]. AB - The study was aimed at evaluation of the effect of dust, produced at crushing the serpentine, on the soil and crops in Naslawice. The serpentine dust, apart from asbestos, contains also magnesium, calcium, chromium and nickel. These elements have been determined in the soil and plants by means of the standard methods generally used in agricultural chemistry, whereas asbestos content was determined by means of X-ray diffractometry and polarization microscopy. The dust of the crops harvested contained asbestos fibres and, in the plants, the increased content of nickel an chromium was found. The highest amount of asbestos was found in soil in the area at a distance of up to 50 km from the emission source. The soil contains also the increased amounts of chromium and sporadically cadmium. PMID- 1406245 TI - [Analysis of the incidence of pneumoconiosis among coal miners]. AB - Basing on the prevention system for pneumoconiosis in ++coal mining, an analysis of the disease incidence in the workers of a selected ++coal mine was performed. The subjects were 2.495 miners with the work period longer than 8 years and a group of 822 retired miners. In the former group 16 cases (0.64%) of pneumoconiosis were diagnosed, whereas in the latter as many as 89 cases (10.8%) were found which would indicate a necessity for more detailed examinations in ex miners of this ++coal mine. The pneumoconiosis changes were detected in the early period of their development. The highest risk was found to refer to longwall and blasting miners and cutter-loadermen. The correlation between radiological changes of the s, t, and u type and the duration of work as well as the high frequency of these changes at highly polluted workplaces seem to point to their relation to dust exposure. PMID- 1406246 TI - Interaction between maltose-binding protein and the membrane-associated maltose transporter complex in Escherichia coli. AB - Active transport of maltose in Escherichia coli requires the presence of both maltose-binding protein (MBP) in the periplasm and a complex of MalF, MalG, and MalK proteins (FGK2) located in the cytoplasmic membrane. Earlier, mutants in malF or malG were isolated that are able to grow on maltose in the complete absence of MBP. When the wild-type malE+ allele, coding for MBP, was introduced into these MBP-independent mutants, they frequently lost their ability to grow on maltose. Furthermore, starting from these Mal- strains, Mal+ secondary mutants that contained suppressor mutations in malE were isolated. In this study, we examined the interaction of wild-type and mutant MBPs with wild-type and mutant FGK2 complexes by using right-side-out membrane vesicles. The vesicles from a MBP independent mutant (malG511) transported maltose in the absence of MBP, with Km and Vmax values similar to those found in intact cells. However, addition of wild type MBP to these mutant vesicles produced unexpected responses. Although malE+ malG511 cells could not utilize maltose, wild-type MBP at low concentrations stimulated the maltose uptake by malG511 vesicles. At higher concentrations of the wild-type MBP and maltose, however, maltose transport into malG511 vesicles became severely inhibited. This behaviour of the vesicles was also reflected in the phenotype of malE+ malG511 cells, which were found to be capable of transporting maltose from a low external concentration (1 microM), but apparently not from millimolar concentrations present in maltose minimal medium. We found that the mutant FGK2 complex, containing MalG511, had a much higher apparent affinity towards the wild-type MBP than did the wild-type FGK2 complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406247 TI - Isolation of phosphorylation-deficient mutants of the Rhizobium meliloti two component regulatory protein, FixJ. AB - Rhizobium meliloti FixL and FixJ are members of a symbiotically essential two component system that regulates nitrogen-fixation genes in response to environmental oxygen concentrations. FixL is a membrane protein that is thought to relay information about oxygen availability to FixJ via a phosphotransfer mechanism. FixJ increases expression of the nifA and fixK genes by activating transcription of the nifA and fixK promoters (p-nifA and p-fixK, respectively). In this study, we examined the relationship between the in vivo activity of FixJ as a transcriptional regulator and its ability to be phosphorylated in vitro by the sensor FixL. FixJ mutants were isolated that showed decreased activity on p nifA in Escherichia coli. Most of the FixJ mutant proteins also showed decreased activity on the fixK promoter. These mutants were analysed in R. meliloti for activity on p-nifA during vegetative growth, where similarities and differences were observed when compared with their phenotypes in E. coli. Three mutants showing significantly less activity in R. meliloti were examined for symbiotic activity in planta and were found to be ineffective. When these three mutant FixJ proteins were examined in vitro for their ability to be phosphorylated by FixL, two mutants were found to have a significantly decreased ability to accept phosphate from FixL. These findings are discussed in relation to signal transduction in the FixLJ system. PMID- 1406248 TI - Homologous catalytic domains in a rumen fungal xylanase: evidence for gene duplication and prokaryotic origin. AB - A cDNA (xynA), encoding xylanase A (XYLA), was isolated from a cDNA library, derived from mRNA extracted from the rumen anaerobic fungus, Neocallimastix patriciarum. Recombinant XYLA, purified from Escherichia coli harbouring xynA, had a M(r) of 53,000 and hydrolysed oat-spelt xylan to xylobiose and xylose. The enzyme did not hydrolyse any cellulosic substrates. The nucleotide sequence of xynA revealed a single open reading frame of 1821 bp coding for a protein of M(r) 66,192. The predicted primary structure of XYLA comprised an N-terminal signal peptide followed by a 225-amino-acid repeated sequence, which was separated from a tandem 40-residue C-terminal repeat by a threonine/proline linker sequence. The large N-terminal reiterated regions consisted of distinct catalytic domains which displayed similar substrate specificities to the full-length enzyme. The reiterated structure of XYLA suggests that the enzyme was derived from an ancestral gene which underwent two discrete duplications. Sequence comparison analysis revealed significant homology between XYLA and bacterial xylanases belonging to cellulase/xylanase family G. One of these homologous enzymes is derived from the rumen bacterium Ruminococcus flavefaciens. The homology observed between XYLA and a rumen prokaryote xylanase could be a consequence of the horizontal transfer of genes between rumen prokaryotes and lower eukaryotes, either when the organisms were resident in the rumen, or prior to their colonization of the ruminant. It should also be noted that Neocallimastix XYLA is the first example of a xylanase which consists of reiterated sequences. It remains to be established whether this is a common phenomenon in other rumen fungal plant cell wall hydrolases. PMID- 1406249 TI - Cell division in Escherichia coli minB mutants. AB - In Escherichia coli minB mutants, cell division can take place at the cell poles as well as non-polarly in the cell. We have examined growth, division patterns, and nucleoid distribution in individual cells of a minC point mutant and a minB deletion mutant, and compared them to the corresponding wild-type strain and an intR1 strain in which the chromosome is over-replicated. The main findings were as follows. In the minB mutants, polar and non-polar divisions appeared to occur independently of each other. Furthermore, the timing of cell division in the cell cycle was found to be severely affected. In addition, nucleoid conformation and distribution were considerably disturbed. The results obtained call for a re evaluation of the role of the MinB system in the E. coli cell cycle, and of the concept that limiting quanta of cell division factors are regularly produced during the cell cycle. PMID- 1406250 TI - Isolation of arginine auxotrophs, cloning by mutant complementation, and sequence analysis of the argC gene from the cyanobacterium Anabaena species PCC 7120. AB - Arginine auxotrophs of the dinitrogen-fixing cyanobacterium Anabaena species strain PCC 7120 were isolated after ultraviolet light mutagenesis and penicillin enrichment. Two of these auxotrophs were complemented by a cosmid gene library of the wild-type strain established in Escherichia coli that was transferred en masse to the mutants by conjugation. The gene complementing one of those mutants was found to complement an E. coli argC mutant. Sequencing analysis of the gene showed that it encodes a 322-residue polypeptide that is homologous to the ArgC protein of E. coli, Bacillus subtilis and Streptomyces clavuligerus and to the C terminal moiety of the Saccharomyces cerevisiae ARG5,6 gene product, N acetylglutamate semialdehyde dehydrogenase. A cysteine residue present in a highly conserved domain in the five proteins is probably located in the active site of the enzyme. Conserved among the ArgC proteins, sequences resembling the primary structure of nucleotide-binding domains are also found. Downstream of the Anabaena argC gene seven nearly perfect repeats of a heptanucleotide (consensus sequence:5'-CTAATGA-3') are found. PMID- 1406251 TI - Localization of an immunodominant 64 kDa lipoprotein (LP 64) in the membrane of Mycoplasma gallisepticum and its role in cytadherence. AB - A 64 kDa lipoprotein (LP 64) haemagglutinin (pI 4.9-5.0) was isolated from the membrane of Mycoplasma gallisepticum. Triton X-114 phase partitioning has demonstrated that the hydrophobic nature of this haemagglutinin is due to a lipid portion of the molecule. Autoradiography of [3H]-palmitate-labelled M. gallisepticum revealed the presence of several additional lipoproteins. Immunoelectron microscopy demonstrated the localization of LP 64 to the base of the terminal structure. Densitometric scans of stained polyacrylamide gels of M. gallisepticum showed that LP 64 constitutes 1.7% of the total protein. Scans of immunoblots of M. gallisepticum indicate that LP 64 is highly immunogenic in chickens, accounting for 7.4% of the total serum IgG response at four weeks post infection. A quantitative value for the IgG response to LP 64, relative to the percentage of total protein (the Relative Immunogenicity Index) was 4.4. LP 64 is conserved among several strains of M. gallisepticum, but its presence could not be detected in Mycoplasma synoviae. Antiserum raised to electroeluted LP 64 reacted specifically with this lipoprotein when assessed on either one- or two dimensional immunoblots of M. gallisepticum. This antiserum, as well as Fab fragments, inhibited haemagglutination of chicken erythrocytes and inhibited the attachment of 14C-labelled M. gallisepticum to chicken tracheal epithelium in vitro by 62%. PMID- 1406252 TI - Temperature regulation of Shigella virulence: identification of the repressor gene virR, an analogue of hns, and partial complementation by tyrosyl transfer RNA (tRNA1(Tyr)). AB - virR is the central regulatory locus required for coordinate temperature regulated virulence gene expression in the human enteric pathogens of Shigella species. Detailed characterization of VirR+ clones revealed that virR consisted of a 411 bp open reading frame (ORF) that mapped to a chromosomally located 1.8kb EcoRI-AccI DNA fragment from Shigella flexneri. Insertional inactivation of the virR ORF at a unique HpaI restriction site resulted in a loss of VirR+ activity. The virR ORF nucleotide sequence was virtually identical to the Escherichia coli hns gene, which encodes the histone-like protein, H-NS. Based on the predicted amino acid sequence of E. coli H-NS, only a single conservative base-pair change was identified in the virR gene. An additional clone, designated VirRP, which only partially complemented the virR mutation, was also characterized and determined by Southern hybridization and nucleotide sequence analysis to be unique from virR. Subclone mapping of this clone indicated that the VirRP phenotype was a result of the multiple copy expression of the S. flexneri gene for tRNA(Tyr). These data constitute the first direct genetic evidence that virR is an analogue of the E. coli hns gene, and suggest a model for temperature regulation of Shigella species virulence via the bacterial translational machinery. PMID- 1406253 TI - Cloning, nucleotide sequence determination and expression of the genes encoding cytochrome P-450soy (soyC) and ferredoxinsoy (soyB) from Streptomyces griseus. AB - Xenobiotic transformation by Streptomyces griseus (ATCC13273) is catalysed by a cytochrome P-450, designated cytochrome P-450soy. A DNA segment carrying the structural gene encoding P-450soy (soyC) was cloned using an oligonucleotide probe constructed from the protein sequence of a tryptic peptide. Following DNA sequencing the deduced amino acid sequence of P-450soy was compared with that for P-450cam, revealing conservation of important structural components including the haem pocket. Expression of the cloned soyC gene product was demonstrated in Streptomyces lividans by reduced CO:difference spectral analysis and Western blotting. Downstream of soyC, a gene encoding a putative [3Fe-4S] ferredoxin (soyB), named ferredoxinsoy, was identified. PMID- 1406254 TI - Sequence diversity within the argF, fbp and recA genes of natural isolates of Neisseria meningitidis: interspecies recombination within the argF gene. AB - Studies of natural populations of Neisseria meningitidis using multilocus enzyme electrophoresis have shown extensive genetic variation within this species, which, it has been proposed, implies a level of sequence diversity within meningococci that is greater than that normally considered as the criterion for species limits in bacteria. To obtain a direct measure of the sequence diversity among meningococci, we obtained the nucleotide sequences of most of the argF, recA and fbp genes of eight meningococci of widely differing electrophoretic type (from the reference collection of Caugant). Sequence variation between the meningococcal strains ranged from 0-0.6% for fbp, 0-1.3% for argF, and 0-3.3% for recA. These levels of diversity are no greater than those found within Escherichia coli 'housekeeping' genes and suggest that multilocus enzyme electrophoresis may overestimate the extent of nucleotide sequence diversity within meningococci. The average sequence divergence between the Neisseria meningitidis strains and N. gonorrhoeae strain FA19 was 1.0% for fbp and 1.6% for recA. The argF gene, although very uniform among the eight meningococcal isolates, had a striking mosaic structure when compared with the gonococcal argF gene: two regions of the gene differed by greater than 13% in nucleotide sequence between meningococci and gonococci, whereas the rest of the gene differed by less than 1.7%. One of the diverged regions was shown to have been introduced from the argF gene of a commensal Neisseria species that is closely related to Neisseria cinerea. The source of the other region was unclear. PMID- 1406255 TI - Isolation and characterization of an ndvB locus from Rhizobium fredii. AB - A gene (ndvB) in Rhizobium meliloti that is essential for nodule development in Medicago sativa (alfalfa), specifies synthesis of a large membrane protein. This protein appears to be an intermediate in beta-1,2-glucan synthesis by the microsymbiont. Southern hybridization analysis showed strong homology between an ndvB (chvB) probe and genomic DNA of R. fredii but not from Bradyrhizobium japonicum. A cosmid clone containing the putative ndvB locus was isolated from a Rhizobium fredii gene library. The cosmid clone which complemented R. meliloti ndvB mutants for synthesis of beta-1,2-glucans and effective nodulation of alfalfa was mapped and subcloned. Fragment-specific Tn5 mutagenesis followed by homologous recombination into the R. fredii genome indicated that the region was essential for beta-1,2-glucan synthesis and for formation of an effective symbiosis with Glycine max (soybean). PMID- 1406256 TI - Chromosomal and genetic analysis of the electrophoretic karyotype of Trichoderma reesei: mapping of the cellulase and xylanase genes. AB - An electrophoretic karyotype has been established for Trichoderma reesei strain QM6a, and several of its derivatives, by pulsed-field gel electrophoresis. All strains examined appear to have seven chromosomes with a total genome size of approximately 33 megabases (Mb). The sizes of the chromosomal bands in strain QM6a are approximately 6.2, 6.0, 5.1, 4.2 (doublet), 3.6 and 3.2 Mb. Genes encoding the cellulase complex and xylanases of T. reesei have been mapped, as have several other genes. PMID- 1406257 TI - Carbon regulation and the role in nature of the Escherichia coli penicillin acylase (pac) gene. AB - Quantitative analysis of specific pac mRNA and a lacZ fusion to the 5'-terminal region of the pac gene demonstrated that both phenylacetic acid induction and catabolite repression by glucose are involved, at the transcriptional level, in the regulation of the pac gene. The studies presented here suggest that this regulation is also present in Escherichia coli transformed strains in which the pac gene was not originally present. Analysis of the nucleotide sequence of the 5'-terminal region of this gene, with a statistical algorithm, confirms that the putative promoter previously proposed by our group is the most feasible within this region. We demonstrate that penicillin acylase activity can confer on E. coli the ability to use penicillin G as a metabolic substrate, by detaching the phenylacetic group which can be used as a carbon source. Based on these data, the regulation properties of the pac gene studied in this work, and the specificity profile of the penicillin acylase enzyme we suggest a role for it in E. coli as a scavenger enzyme for phenylacetylated compounds. PMID- 1406258 TI - Osmostress-induced changes in yeast gene expression. AB - When Saccharomyces cerevisiae cells are exposed to high concentration of NaCl, they show reduced viability, methionine uptake and protein biosynthesis. Cells can acquire tolerance against a severe salt shock (up to 1.4 M NaCl) by a previous treatment with 0.7 M NaCl, but not by a previous heat shock. Two dimensional analysis of [3H]-leucine-labelled proteins from salt-shocked cells (0.7 M NaCl) revealed the elevated rate of synthesis of nine proteins, among which were the heat-shock proteins hsp12 and hsp26. Northern analysis using gene specific probes confirmed the identity of the latter proteins and, in addition, demonstrated the induction of glycerol-3-phosphate dehydrogenase gene expression. The synthesis of the same set of proteins is induced or enhanced upon exposure of cells to 0.8 M sucrose, although not as dramatically as in an iso-osmolar NaCl concentration (0.7 M). PMID- 1406259 TI - Decreasing transcription elongation rate in Escherichia coli exposed to amino acid starvation. AB - The time required for transcription of the lacZ gene in Escherichia coli was determined during exponential growth and under conditions, when the bacterium was exposed to partial isoleucine starvation. To do this, RNA was extracted from the cells at 10 s intervals following induction and quantified by Northern hybridization with probes complementary to either the beginning or the end of the lacZ mRNA. The time lag between inducer addition and the appearance of a hybridization signal at the 'late' probe represents the transit time for RNA polymerase on the lacZ gene, and this parameter and the known length of the transcribed sequence were used to calculate the lacZ mRNA chain growth-rate. The transcription elongation rate was c. 43 nucleotides s-1 during exponential growth and decreased abruptly to c. 20 nucleotides s-1 in a relA+ strain after the onset of isoleucine starvation, when massive concentrations of guanosine tetraphosphate (ppGpp) accumulated in the cells. The starvation condition did not affect initiation of transcription at the lac-promoter, but a substantial fraction of the initiated lacZ mRNA chains was never completed. For the rel+ strain the polarity was moderate, since c. 25% of the initiated lacZ mRNA' chains were continued into full-length mRNAs, but for the relA strain the polarity was so strong that no completed lacZ mRNA could be detected. The protein chain elongation rates decreased from 13 amino acids (aa) s-1 in the unperturbed growth phase to approximately 6 as s-1, when the cells starved for isoleucine. In combination, these results suggest that ppGpp plays a major role in maintaining the coupling between transcription and translation during the downshift by inhibiting mRNA chain elongation. The implications of this result for the control of stable RNA synthesis during the stringent response are discussed. PMID- 1406260 TI - Disulphide bridge formation in the periplasm of Escherichia coli: beta lactamase:: human IgG3 hinge fusions as a model system. AB - We report the construction and the expression in Escherichia coli of three different fusion genes encoding the extended human IgG3 hinge region (Hi) fused in-phase to the C-terminal end of bacterial TEM1 beta-lactamase (Bla). In the first fusion gene blahi, TEM1 beta-lactamase (Bla). In the first fusion gene blahi, the hinge sequence was directly coupled to the 3' end of the beta lactamase gene, whereas in the two other constructs, blal1hi and blal2hi, a linker encoding 14 and 10 amino acids, respectively, was inserted between the two subunits. After expression (24 h, 20 degrees C) under control of the constitutive kanamycin phosphoribosyl transferase promoter, the fusion proteins, BlaHi, BlaL1Hi and BlaL2Hi, respectively, were almost exclusively detected in the periplasmic fraction, and they conferred carbenicillin-resistance to the cells. These results indicate that beta-lactamase can efficiently direct the export of proteins fused to its C-terminus, and moreover, at least some of the exported fusion proteins must carry the beta-lactamase moiety in a properly folded form. Analysis of their assembly, however, revealed that only a minor fraction was recovered as the expected F(ab')2-like dimer. The presence in the periplasm of 'oxidized' monomers (with intrachain disulphide bonds) as well as of several high molecular-mass proteins, probably resulting from the association between monomers and other cysteine-rich proteins, strongly suggests that the conditions in the bacterial periplasm are insufficient to allow proper assembly of multimeric proteins with several interchain disulphide bonds. PMID- 1406261 TI - Thermoregulation and reversible differentiation in Bordetella: a model for pathogenic bacteria. PMID- 1406262 TI - Protein sequence from downstream of Escherichia coli galK is homologous with galM from other organisms. PMID- 1406263 TI - Mutagenesis induced by bacterial UmuDC proteins and their plasmid homologues. AB - The popular image of a world full of pollutants mutating DNA is only partly true since there are relatively few agents which can subtly and directly change base coding; for example, some alkylating agents alter guanine so that it pairs like adenine. Many more mutagens are less subtle and simply destroy coding altogether rather than changing it. Such mutagens include ultraviolet light, X-rays, DNA cross-linkers and other agents which make DNA breaks or large adducts. In Escherichia coli, mutagenesis by these agents occurs during a DNA repair process which increases cell survival but with an inherent possibility of changing the original sequence. Such mutagenic DNA repair is, in part, encoded by the E. coli umuDC operon. This article reviews the structure, function, regulation and evolution of the umuDC operon and similar genes found both in other species and on naturally occurring plasmids. PMID- 1406264 TI - (A)BC excinuclease: the Escherichia coli nucleotide excision repair enzyme. AB - Nucleotide excision repair is the major pathway for removing damage from DNA. (A)BC excinuclease is the nuclease activity which initiates nucleotide excision repair in Escherichia coli. In this review, we focus on current understanding of the structure-function of the enzyme and the reaction mechanism of the repair pathway. In addition, recent biochemical studies on preferential repair of actively transcribed genes in E. coli are summarized. PMID- 1406265 TI - Interrelated effects of DNA supercoiling, ppGpp, and low salt on melting within the Escherichia coli ribosomal RNA rrnB P1 promoter. AB - The formation of complexes containing high levels of DNA melting at the ribosomal RNA rrnB P1 promoter in vitro is shown to be facilitated by DNA supercoiling or low salt. The effector nucleotide ppGpp is ineffective under these conditions. The loss of supercoils or addition of salt increases the effectiveness of ppGpp in inhibiting formation of these complexes. In vivo plasmid DNA supercoiling is shown to decrease during starvation protocols that also increase levels of ppGpp. The results suggest that ppGpp regulation may be affected by the state of DNA supercoiling in vivo. PMID- 1406266 TI - Surface protein-CAT reporter fusions demonstrate differential gene expression in the vir regulon of Streptococcus pyogenes. AB - Streptococcus pyogenes expresses at least two virulence factors, the anti phagocytic M protein and an inhibitor of chemotaxis, the C5a peptidase (ScpA), under control of the virR locus. To facilitate studies of this regulatory unit, we constructed a new shuttle vector with a staphylococcal chloramphenicol acetyl transferase (CAT) reporter box which replicates in S. pyogenes. We cloned polymerase chain reaction (PCR)-derived potential promoter regions of the virR, M protein (emm12), and ScpA (scpA) genes from an M type 12 S. pyogenes, strain CS24. Promoter activity was assessed by measurements of specific mRNAs, transacetylase activity, and minimum inhibitory concentrations (MICs) for chloramphenicol resistance. We demonstrated that VirR is a necessary but not always sufficient positive trans-acting regulator of emm12 and scpA expression; however, virR is not autoregulated. A potential virR-binding consensus sequence is postulated for emm12, scpA and other M-like protein genes. Promoter activity of the structural genes was found to be dramatically influenced by growth conditions such as anaerobiosis. Levels of control, over and above the requirement for virR, are realized. The virR and scpA promoters were mapped for the first time using primer extension analysis. The observed mRNA start sites did not completely agree within the sequence predicted start sites. Data suggest that scpA could be subject to transcription attenuation. PMID- 1406267 TI - A metalloprotease gene from Streptomyces coelicolor 'Muller' and its transcriptional activator, a member of the LysR family. AB - A metalloprotease gene (mprA) and its regulatory gene (mprR) from Streptomyces coelicolor 'Muller' DSM3030 were isolated and their DNA sequences determined. The protease secreted by the heterologous host Streptomyces lividans was characterized biochemically as a metalloprotease with a M(r) of 20,000, which is in good agreement with data derived from DNA sequence analysis. The mprA gene is transcribed divergently from mprR, the deduced protein of which displays homology to prokaryotic transcriptional regulators of the LysR family. The regulatory protein (MprR) was shown to bind to the intergenic region between mprR and mprA. It was found to activate transcription of mprA in S. lividans and also in Escherichia coli. PMID- 1406268 TI - Ethanol-induced and glucose-insensitive alcohol dehydrogenase activity in the yeast Kluyveromyces lactis. AB - The alcohol dehydrogenase (ADH) system in the yeast Kluyveromyces lactis is encoded by four ADH genes. In this paper we report evidence that at least three of these genes are transcribed and translated into protein. KIADH1 and KIADH2, which encode cytoplasmic activities, are preferentially expressed in glucose grown cells with respect to ethanol-grown cells. KIADH4, which encodes one of the two activities localized within mitochondria, is induced at the transcriptional level in the presence of ethanol as is the ADH2 gene in Saccharomyces cerevisiae. However the regulation of the expression of the K. lactis gene is completely different from that of ADH2 and of other known ADH genes in that KIADH4 is insensitive to glucose repression and is not expressed on non-fermentable carbon sources other than ethanol. This kind of regulation can be clearly observed in non-fermenting strains, where the induction of KIADH4 is dependent on the addition of ethanol to the medium. On the contrary, in fermenting strains KIADH4 is always induced by ethanol or acetaldehyde produced endocellularly and this results in constitutive expression of the gene also in the presence of glucose. The mitochondrial localization of the activity encoded by KIADH4 and the peculiar regulation of this gene could be related to the fact that K. lactis is a petite negative yeast in which some mitochondrial functions seem to be essential for cell viability. PMID- 1406269 TI - Identification of a novel large extrachromosomal DNA (LED) in the Trypanosomatidae. AB - We have identified a novel 75 kbp large extrachromosomal DNA (LED) which is stably maintained during developmental conversion of Trypanosoma cruzi. It has a covalently closed circular conformation and is not derived from the kinetoplast network. In all T. cruzi strains analysed, LED contains 18S rRNA and spliced leader (sl) sequences. LED from the T. cruzi Y strain contains a minimum of 15 copies of the sl repeat arrayed in a head-to-tail configuration and 50 copies of a 196 bp repeat. LED is also present in Trypanosoma dionisii (subgenus Schizotrypanosoma) and in other members of the family Trypanosomatidae. LED from different T. cruzi strains and from other members of the Trypanosomatidae differ in their content of large ribosomal subunit rRNA sequences and the 196 bp repeat. The presence of LED in four evolutionarily distant trypanosomatid species suggests that it plays an important role in the biology of these parasites. PMID- 1406270 TI - The stable BRP signal peptide causes lethality but is unable to provoke the translocation of cloacin DF13 across the cytoplasmic membrane of Escherichia coli. AB - The bacteriocin release protein (BRP) mediates the secretion of cloacin DF13. The BRP precursor is slowly processed to yield the mature BRP and its stable signal peptide which is also involved in cloacin DF13 secretion. The function of the stable BRP signal peptide was analysed by constructing two plasmids. First, the stable BRP signal peptide was fused to the murein lipoprotein and, second, a stop codon was introduced after the BRP signal sequence. Exchange of the unstable murein lipoprotein signal peptide for the stable BRP signal peptide resulted in an accumulation of precursors of the hybrid murein lipoprotein. This indicated that the BRP signal peptide, as part of this hybrid precursor, is responsible for the slow processing. The stable BRP signal peptide itself was not able to direct the transfer of cloacin DF13 into the periplasmic space or into the culture medium. Over-expression of the BRP signal peptide was lethal and caused 'lysis'. Subcellular fractionation experiments revealed that the BRP signal peptide is located exclusively in the cytoplasmic membrane whereas the mature BRP, targeted by either the stable BRP signal peptide or the unstable Lpp signal peptide, is located in both the cytoplasmic and outer membrane. These results are in agreement with the hypothesis that the stable signal peptide and the mature BRP together are required for the passage of cloacin DF13 across the cell envelope. PMID- 1406271 TI - Polyphosphate-selective porin OprO of Pseudomonas aeruginosa: expression, purification and sequence. AB - The oprO gene of Pseudomonas aeruginosa codes for a polyphosphate-specific porin and terminates 458 bp upstream of the start codon for the phosphate-specific porin OprP. OprO was found to be expressed only under phosphate-starvation conditions in both wild-type and oprP::Tn501 mutant P. aeruginosa strains. However, unlike the rest of the genes of the Pho regulon, including oprP, expression of oprO required cells to be in the stationary growth phase in addition to phosphate starvation. Wild-type P. aeruginosa cells were grown in fermentor culture under these conditions and fractionated by selective solubilization in octylpolyoxyethylene detergent solution. Solubilized OprO was separated from OprP by application to a Mono Q FPLC column and elution with a salt gradient and shown to be functionally identical to cloned OprO produced in Escherichia coli. DNA sequencing of oprO showed the gene product to be highly homologous to OprP, with 76% identity and 16% conserved substitutions. Most genes of the Pho regulon possess a modified -35 region called the Pho box. Two such elements, separated by 4 bp were found in oprO. DNA sequencing also revealed a second Pho box in the oprP gene with the same spacing. PMID- 1406272 TI - Expression and mutational analysis of the nucleoid-associated protein H-NS of Salmonella typhimurium. AB - The H-NS (H1) protein is a major component of bacterial chromatin. Mutations in the hns (osmZ) gene encoding H-NS are highly pleiotropic, affecting the expression of many unrelated genes in an allele-specific manner. H-NS expression was found not to vary with growth phase or growth medium osmolarity. Additionally, 10 independent hns mutations were isolated and characterized. Five of these mutations were the result of an IS10 insertion, each generating a truncated polypeptide. The other five mutations were the same specific deletion of one amino acid, delta Ala46. The various hns mutations exhibited different phenotypes and influenced DNA topology to variable extents. Implications for the mechanism by which H-NS influences gene expression are discussed. PMID- 1406273 TI - The effects of 5'-capping, 3'-polyadenylation and leader composition upon the translation and stability of mRNA in a cell-free extract derived from the yeast Saccharomyces cerevisiae. AB - A new modular expression system was developed to direct the in vitro synthesis of defined transcripts that were used as templates for translation in yeast cell free extracts. The system was used to examine the influence of 5'-capping, 3' polyadenylation and leader sequence upon the translation and stability of the synthetic Tn9 cat (chloramphenicol acetyl transferase), yeast PGK (phosphoglycerate kinase) and yeast HSP26 (heat-shock protein 26) mRNAs. The addition of a methylated cap (m7Gppp) or of a poly(A) tail enhanced translation and stabilized the mRNA. The dependence of translation upon capping was reduced in the presence of the HSP26 leader sequence. This may indicate the existence of a translational mechanism that enhances cap-independent translation. The enhancement of the translation and stability of mRNA was relatively insensitive to changes in the position of the poly(A) tail relative to the reading frame. PMID- 1406274 TI - Cloning and nucleotide sequence of the csp1 gene encoding PS1, one of the two major secreted proteins of Corynebacterium glutamicum: the deduced N-terminal region of PS1 is similar to the Mycobacterium antigen 85 complex. AB - Two proteins, PS1 and PS2, were detected in the culture medium of Corynebacterium glutamicum and are the major proteins secreted by this bacterium. No enzymatic activity was identified for either of the two proteins. Immunologically cross reacting proteins were found in a variety of C. glutamicum strains but not in the coryneform Arthrobacter aureus. The gene encoding PS1, csp1, was cloned in lambda gt11 using polyclonal antibodies raised against PS1 to screen for producing clones. The csp1 gene was expressed in Escherichia coli, presumably from its own promoter, and directed the synthesis of two proteins recognized by anti-PS1 antibodies. The major protein band, of lower M(r), was detected in the periplasmic fraction. It had the same M(r) as the PS1 protein band detected in the supernatant of C. glutamicum cultures and presumably corresponds to the mature form of PS1. The minor protein band appears to be the precursor form of PS1. The nucleotide sequence of the csp1 gene was determined and contained an open reading frame encoding a polypeptide with a calculated molecular weight of 70,874, with a putative signal peptide with a molecular weight of 4411. This is consistent with the M(r) determined for PS1 from C. glutamicum culture supernatant and E. coli whole-cell extracts. The NH2-half of the deduced amino acid is similar (about 33% identical residues and 52% including similar residues) to the secreted antigen 85 protein complex of Mycobacterium. The csp1 gene in C. glutamicum was disrupted without any apparent effect on growth or viability. PMID- 1406275 TI - Analysis of the regulation of the pelBC genes in Erwinia chrysanthemi 3937. AB - Erwinia chrysanthemi secretes five major isoenzymes of pectate lyases encoded by the pelABCDE genes. The nucleotide sequence of the region surrounding the pelB gene of E. chrysanthemi 3937 was determined, including the regulatory regions involved in pelB and pelC expression. Analysis of the transcripts showed that transcription of pelB or pelC gave, in both cases, only one transcript. The transcription initiation sites of both pelB and pelC were precisely determined as well as the position of the transcription termination of pelB. The pelB and pelC promoters are very similar, showing a good homology with the -35 consensus region but low homology with the -10 consensus. In both cases a KdgR-box overlaps the 35 region. The pelC gene may have two KdgR operators. Moreover, the pelB and pelC genes are preceded by other sequences presenting the typical symmetry of operator sites that could be involved in more specific regulations. Comparison of E. chyrsanthemi pel regulatory regions revealed three classes of homology: pelA, pelB-pelC and pelD-pelE. The sole regulatory sequence conserved among the three classes corresponds to the KdgR-binding site. Moreover, all the pel regulatory regions are AT-rich in contrast to the coding regions which are GC-rich. Gel retardation experiments with fragments overlapping the pelB or pelC regulatory regions demonstrated that the KdgR protein specifically binds to these regions. Other proteins probably also interact with these DNA fragments. Transcription of pelB terminates in a region corresponding to a GC-rich inverted repeat followed by a run of T residues, typical of rho-independent transcription termination sites. Moreover, preliminary results imply that a region adjacent to pelC provoke, directly or indirectly, the repression of pelB and pelC expression. PMID- 1406276 TI - The plasmid-encoded chloramphenicol-resistance protein of Rhodococcus fascians is homologous to the transmembrane tetracycline efflux proteins. AB - The nucleotide sequence of the chloramphenicol-resistance gene (cmr) of Rhodococcus fascians NCPPB 1675 (located on the conjugative plasmid pRF2) allowed the identification of two possible open reading frames (ORFs), of which ORF1 was consistent with the mutational analysis. Biochemical analysis of cmr revealed that it does not encode an antibiotic-modifying enzyme. The amino acid sequence of ORF1 predicted a hydrophobic protein, with 12 putative membrane-spanning domains, homologous to proteins involved in the efflux of tetracycline across the plasma membrane. Expression of the cmr gene was induced by addition of chloramphenicol to the growth media. The promoter of this gene was restricted to 50 bp upstream from a 200 bp 5'-untranslated mRNA region, the latter containing two inverted repeats. At the amino acid level, the cmr gene is 52% identical to a previously identified chloramphenicol-resistance determinant in Streptomyces lividans, indicating a wider dispersion of this type of cmr gene among the actinomycetes. PMID- 1406277 TI - Identification and characterization of virK, a virulence-associated large plasmid gene essential for intercellular spreading of Shigella flexneri. AB - Seven virulence loci have been identified by Tn5 insertion mutagenesis on the large 230 kb plasmid (pMYSH6000) of Shigella flexneri 2a. In this study, we used Tn10 insertion mutagenesis and identified a novel virulence locus on pMYSH6000 responsible for bacterial spread. Characterization of the invading bacteria of the Tn10 insertion mutants in the epithelial cells revealed that the bacteria were capable of at least some intracellular spreading but not intercellular spreading. Immunoblot analysis of lysates of the Tn10 insertion mutants with a VirG-specific antipeptide antibody revealed diminished levels of the 116 kDa VirG protein. The virG mRNA in the mutants, however, was expressed at the same level as that in the wild type. The DNA region required for the virulence phenotype was localized to a 1.6 kb DNA sequence in the SalI-K fragment on the plasmid, and thus the locus was designated virK. Expression of virK in Escherichia coli using a T7 RNA polymerase-dependent promoter system yielded a 36 kDa protein. The nucleotide sequence of 1642 bp encoding VirK function was determined, and an open reading frame encoding 316 amino acid residues was shown to encode the VirK protein. The virK region was highly conserved among the large virulence plasmids of shigellae and enteroinvasive Escherichia coli. These results suggest that VirK function is an essential virulence determinant for shigellae involved in the expression of virG gene product at post-transcriptional level. PMID- 1406278 TI - Purification of the STB enterotoxin of Escherichia coli and the role of selected amino acids on its secretion, stability and toxicity. AB - The methanol-insoluble heat-stable enterotoxin of Escherichia coli (STB) was purified and characterized by automated Edman degradation and tryptic peptide analysis. The amino-terminal residue, Ser-24, confirmed that the first 23 amino acids inferred from the gene sequence were removed during translocation through the E. coli inner membrane. Tryptic peptide analysis coupled with automated Edman degradation revealed that disulphide bonds are formed between residues Cys-33 and Cys-71 and between Cys-44 and Cys-59. Oligonucleotide-directed mutagenesis performed on the STB gene demonstrated that disulphide bond formation does not precede translocation of the polypeptide through the inner membrane and that disulphide bridge formation is a periplasmic event; apparently, elimination of either of two disulphides of STB renders the molecule susceptible to periplasmic proteolysis. In addition, a loop defined by the Cys-44-Cys-59 bond contains at least two amino acids (Arg-52 and Asp-53) required for STB toxic activity. PMID- 1406279 TI - Characterization of a Vibrio cholerae virulence factor homologous to the family of TonB-dependent proteins. AB - IrgA is an iron-regulated virulence factor for infection in an animal model with classical Vibrio cholerae strain 0395. We detected gene sequences hybridizing to irgA at high stringency in clinical isolates in addition to 0395, including another classical strain of V. cholerae, three V. cholerae strains of the El Tor biotype, three non-O1 isolates of V. cholerae, and individual isolates of Vibrio parahaemolyticus, Vibrio fluvialis, and Vibrio alginolyticus. No hybridization to irgA was seen with chromosomal DNA from Vibrio vulnificus or Aeromonas hydrophila. To verify that irgA is the structural gene for the major iron regulated outer membrane protein of V. cholerae, we determined the amino-terminal sequence of this protein recovered after gel electrophoresis and demonstrated that it corresponds to the amino acid sequence of IrgA deduced from the nucleotide sequence. Gel electrophoresis showed that two El Tor strains of V. cholerae had a major iron-regulated outer membrane protein identical in size and appearance to IrgA in strain 0395, consistent with the findings of DNA hybridization. We have previously suggested that IrgA might be the outer membrane receptor for the V. cholerae siderophore, vibriobactin. Biological data presented here, however, show that a mutation in irgA had no effect on the transport of vibriobactin and produced no defect in the utilization of iron from ferrichrome, ferric citrate, haemin or haemoglobin. The complete deduced amino acid sequence of IrgA demonstrated homology to the entire class of Escherichia coli TonB dependent proteins, particularly Cir. Unlike the situation with Cir, however, we were unable to demonstrate a role for IrgA as a receptor for catechol-substituted cephalosporins. The role of IrgA in the pathogenesis of V. cholerae infection, its function as an outer membrane receptor, and its potential interaction with a TonB-like protein in V. cholerae remain to be determined. PMID- 1406280 TI - SecY and integral membrane components of the Escherichia coli protein translocation system. AB - Genetic approaches can address the question of how integral membrane Sec factors interact with each other and facilitate protein translocation across the cytoplasmic membrane of E. coli. This review summarizes genetic analyses of SecY, SecE and some other protein translocation factors, utilizing 'prl' mutations, 'sec' mutations, 'suppressor-directed inactivation', 'Sec titration', dominant negative mutations and their suppressors. Evidence suggests that co-ordinate participation of SecY, SecE, SecD, SecF, and probably some other factors, is crucial for the process. PMID- 1406281 TI - Stress-induced proteolysis in yeast. AB - Survival of cells in their natural environment is crucially dependent on their ability to adapt to constantly occurring changes. The ability of cells to respond to extremes of environmental influences is vital to survival. Proteolysis is a central cellular tool in stress response. Proteins of pathways necessary for normal growth, but harmful under stress conditions, as well as proteins damaged by stress have to be eliminated. The yeast Saccharomyces cerevisiae, a model eukaryote, has evolved two different proteolytic systems: (i) a membrane enveloped, vacuolar (lysosomal) system, which contains a variety of non-specific peptidases and (ii) highly specific peptidases residing at different cellular locations. The best characterized peptidase of the specific system is proteinase yscE, the proteasome equivalent found in all eukaryotic cells. Both the vacuolar and the non-vacuolar systems are vital components of the stress response in yeast. PMID- 1406282 TI - Isolation and characterization of the aadA aminoglycoside-resistance gene from Salmonella choleraesuis. AB - The streptomycin- and spectinomycin-resistance gene of Salmonella choleraesuis was cloned and its nucleotide sequence determined. The gene is 789 bases long, encoding a protein of a predicted size of 29,353 Da. The gene product inactivated streptomycin and spectinomycin by an adenylation modification. It is homologous (c. 40% total identity) to streptomycin adenylyltransferase, a 3'(9)-O nucleotidyltransferase (AAD(3')(9)), which is encoded by the aadA gene in Escherichia coli, Agrobacterium tumefaciens, Klebsiella pneumonia, and Serratia marcescens. The AadA protein of S. choleraesuis differs significantly from the other AadA proteins, indicating that it may have diverged from the other members of this family earlier in evolution. Southern hybridization analysis revealed that homologous aadA sequences were also present in other streptomycin-resistant Salmonella species. PMID- 1406283 TI - Genetics of resistance to third-generation cephalosporins in clinical isolates of Streptococcus pneumoniae. AB - Resistance to third-generation cephalosporins in a clinical isolate of Streptococcus pneumoniae was shown to be due to the production of altered forms of penicillin-binding proteins (PBPs) 2X and 1A. The cloned PBP2X gene from the resistant strain was able to transform a susceptible strain to an intermediate level of resistance. The resulting transformant could be transformed to the full level of resistance of the clinical isolate using the cloned PBP1A gene from the latter strain. Chromosomal DNA from the resistant strain (and from other resistant strains) could readily transform a susceptible strain to the full level of resistance to third-generation cephalosporins (greater than 250-fold for cefotaxime; greater than 100-fold for ceftriaxone) in a single step (transformation frequency of about 10(-5)). The resistant transformants obtained with chromosomal DNA were shown by gene fingerprinting to have gained both the PBP1A and PBP2X genes from the DNA donor. PMID- 1406284 TI - The DNA supercoiling-sensitive expression of the Salmonella typhimurium his operon requires the his attenuator and is modulated by anaerobiosis and by osmolarity. AB - Bacterial cells possess a subset of genes whose expression correlates with changes in DNA supercoiling brought about by anaerobic growth and by growth at high osmolarity. It has been shown previously that expression of the histidine biosynthetic operon of Salmonella typhimurium is derepressed by relaxation of supercoiled DNA. Here, we confirm that a his::MudJ operon fusion in S. typhimurium can be induced by treatment with the DNA gyrase inhibitor novobiocin in a dose-dependent manner, and show that the level of derepression is higher in stationary phase than in mid-exponential phase cultures. Furthermore, expression of his is repressed by anaerobiosis and by osmolarity, two environmental parameters which increase the negative supercoiling of bacterial DNA. Novobiocin induction of his is also repressed by growing the cells either at high osmolarity or anaerobically. Both environmental repression and novobiocin induction of his require the his attenuator. In addition, derepression of his expression by novobiocin and its repression by anaerobiosis or osmolarity are independent of the stringent response gene, relA. PMID- 1406285 TI - The class 1 outer membrane protein of Neisseria meningitidis produced in Bacillus subtilis can give rise to protective immunity. AB - The class 1 outer membrane protein of Neisseria meningitidis B:15:P1.7,16 was expressed in Bacillus subtilis in high yield as intracellular aggregates. These were easy to isolate and the protein (called BacP1) could be solubilized under denaturing conditions. Sera of mice immunized with thus-solubilized BacP1 contained high titres of antibodies that reacted with the class 1 protein of the meningococcal envelope in immunoblots but did not react with native meningococcal envelope in enzyme immunoassays (EIA) or with intact meningococci in bactericidal assays. However, when the BacP1 protein was complexed with heterologous (Salmonella) lipopolysaccharide, the ensuing sera reacted with meningococcal envelope preparations in both EIA and immunoblots, showed subtype-specific bactericidal activity, and were protective in an infant rat meningitis model. PMID- 1406286 TI - Fur regulation in Yersinia species. AB - The effects of iron have been linked with several phenomena including regulation of membrane proteins; however, the mechanism of iron regulation is not well characterized in Yersinia pestis. It is well known that in Escherichia coli, the fur gene product mediates negative transcriptional regulation of several genes in response to iron. We have cloned a Y. pestis fur gene which is highly homologous to the E. coli fur regulatory gene. The sequence of the Y. pestis fur gene exhibits 75% homology to the E. coli gene at the nucleotide level, and 84% homology at the predicted amino acid level. The Y. pestis fur gene is transcribed as a single gene message of approximately 0.5 kb which encodes an approximately 16 kDa protein when expressed in E. coli minicells. A Yersinia enterocolitica fur mutant exhibits hypersensitivity to the Y. pestis bacteriocin, pesticin; the cloned Y. pestis fur gene restores wild-type levels of pesticin sensitivity. Furthermore, iron regulation of at least five surface proteins in this Y. enterocolitica fur mutant is restored by transcomplementation with the Y. pestis fur gene. These data indicate that Y. pestis and Y. enterocolitica possess homologous Fur systems which regulate expression of proteins in response to iron availability. PMID- 1406287 TI - Quantitative determination of FtsA at different growth rates in Escherichia coli using monoclonal antibodies. AB - FtsA is an essential cell division protein in Escherichia coli. Its synthesis in low amounts makes the investigation of its functions difficult. Partially purified FtsA protein was obtained by solubilizing cellular inclusion bodies after overexpression of the ftsA gene for the purpose of raising monoclonal antibodies. Mice were immunized with this FtsA protein fraction and their spleen cells were fused to Sp2/0-AG14 mouse myeloma cells. Hybrid cells were screened and two clones were positively identified as FtsA monoclonal antibody producers by enzyme-linked immunosorbent assay and Western blotting. A quantitative assay using these monoclonal antibodies indicated that the average number of FtsA molecules per cell to be between 50 and 200. However, the concentration of FtsA protein normalized to total cell protein was constant over a wide range of growth rates. This finding is in agreement with the hypothesized role of FtsA protein as a stoichiometric component of the septum. PMID- 1406288 TI - RecA protein of Escherichia coli and chromosome partitioning. AB - Escherichia coli cells deficient in RecA protein frequently contain an abnormal number of chromosomes after completion of ongoing rounds of DNA replication. This suggests that RecA protein may be required for correct timing of initiation of DNA replication; however, we show here that initiation of DNA replication is properly timed in recA mutants. We also find that more than 10% of recA mutant cells contain no DNA. These anucleate cells appear to arise from partitioning of all the DNA into one daughter cell and no DNA into the other daughter cell. Based on these and previously published results, we propose that RecA protein is required for equal partitioning of chromosomes into the two daughter cells. PMID- 1406289 TI - Chlamydia trachomatis Mip-like protein. AB - A 27 kDa Chlamydia trachomatis Mip-like protein with homology of a 175-amino-acid C-terminal fragment to the surface-exposed Legionella pneumophila mip-gene product has previously been described. In this paper the entire chlamydia Mip like sequence of C. trachomatis serovar L2 (lymphogranuloma venereum (LGV) biovar) is presented. The sequence shows high similarity to the legionella Mip protein and its C-terminal region, like that of the legionella Mip, has high amino acid similarity to eukaryotic and prokaryotic FK506-binding proteins. The chlamydial mip-like gene was detected by polymerase chain reaction (PCR) in other C. trachomatis serovars and by sequencing of the mip-like genes of serovars B and E (trachoma biovar) was shown to be highly conserved within the two major biovars of C. trachomatis. Monoclonal and polyclonal antibodies raised against the recombinant Mip-like protein failed to demonstrate surface-exposed epitopes on infectious elementary bodies or reproductive reticulate body forms either by immunofluorescence or immuno-gold electron microscopy. However, a complement dependent inhibition of up to 91% of infectivity for cell cultures was observed with antibodies to the N-terminal fragment of the Mip-like protein suggesting that antibody-accessible epitopes are present on infectious EBs. PMID- 1406290 TI - Partial care in mental health organizations: United States and each state, 1988. AB - Partial care is a relatively new and rapidly-growing form of mental health care consisting of a planned program of mental health treatment services generally provided in visits of 3 or more hours to groups of patients/clients. In 1970, only one-fourth of U.S. mental health organizations provided partial care services, and patient additions to partial care programs were 56 per 100,000 civilian population. By 1988, close to half of all mental health organizations provided partial care services, and the rate of additions was more than 5 times as high. However, large increases in the number or organizations providing partial care between 1984 and 1988 are due in part to changes in definitions that are elaborated on later in the report. In 1988, multiservice mental health organizations were the most numerous providers of partial care with 1,230 of 1,310 (94 percent) providing this program. This was followed by general hospital mental health services with 332 of 1,489 (22 percent) providing partial care and private psychiatric hospitals with 236 of 447 (53 percent) providing this program. Mental health organizations providing partial care were most numerous in populous States, particularly in California (with 187 mental health organizations providing partial care), New York (174 organizations), and Pennsylvania (131 organizations). There were 212,196 patients on the rolls of partial care programs of mental health organizations in the United States (including Territories) at the beginning of 1988, and 286,715 patients were added to these programs during the year. Multiservice mental health organizations were responsible for a majority of both patients on the rolls and patient additions during the year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406291 TI - Increase in cardiac muscle fructose content in streptozotocin-induced diabetic rats. AB - To evaluate the activation of the sorbitol pathway in cardiac muscle in diabetic rats, we measured sorbitol, fructose, and myo-inositol content in cardiac tissue obtained from control and streptozotocin-diabetic rats, with or without an 8-week insulin treatment, using gas chromatography-mass spectrometry (GC-MS). Cardiac fructose and sorbitol content in 10-week diabetic rats increased by 60-fold and 3.9-fold of those of control rats, respectively (P less than .001). In contrast, cardiac myo-inositol content in 10-week diabetic rats decreased to 56% (P less than .025) of the control value. The abnormalities in cardiac fructose, sorbitol, and myo-inositol content were completely normalized by the 8-week insulin treatment, which was initiated 2 weeks after the induction of diabetes. There was no difference in cardiac aldose reductase activity between control and diabetic rats. However, cardiac sorbitol dehydrogenase activity in diabetic rats was 151% (P less than .005) higher than that of control rats, although hepatic sorbitol dehydrogenase activity was not different between the two groups. These results indicate that the sorbitol pathway is significantly activated in cardiac tissue obtained from streptozotocin-induced diabetic rats, which results in the marked cardiac accumulation of fructose. PMID- 1406292 TI - Effect of insulin on impaired antioxidant activities in aortic endothelial cells from diabetic rabbits. AB - The defense system of aortic endothelial cells against oxidative stress was studied in alloxan-induced diabetic rabbits, and the effect of insulin on the antioxidant activities was estimated. Endothelial cells were prepared from 10 diabetic rabbits, 18 diabetic rabbits treated with insulin, and 10 age-matched controls after 17 days of diabetes. These cells were used for the estimation of glutathione (GSH) levels and its related enzyme activities. The antioxidant activities in these endothelial cells from diabetic rabbits were compared with those from control subjects. The concentration of GSH decreased in diabetic rabbits (1.6 +/- 0.2 nmol/mg protein [mean +/- SD] v 3.7 +/- 0.6 nmol/mg protein). Decreases in the activities of Cu, Zn-superoxide dismutase (Cu,Zn-SOD) (62.7 +/- 11.0 U/mg protein v 172.9 +/- 20.2 U/mg protein), catalase (7.6 +/- 2.1 U/mg protein v 12.3 +/- 3.2 U/mg protein), and GSH peroxidase (134.0 +/- 27.0 mU/mg protein v 179.1 +/- 26.2 mU/mg protein) were observed. The activities of other GSH-related enzymes such as GSH S-transferase or GSH reductase did not change in endothelial cells from diabetic rabbits. Most of these antioxidant activities were prevented when diabetic rabbits were treated with insulin (1 to 2 U/kg/d). These antioxidant activities were also determined in the diabetic liver and kidney. Similar decreases in the cellular defense activities and prevention of the decrease in activities by insulin were observed in the diabetic liver, while these antioxidant enzyme activities in the kidney were resistant to diabetic conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406293 TI - Composition of weight loss in severely obese women: a new look at old methods. AB - Seven severely obese, outpatient dieters lost weight (mean +/- SEM, 14 +/- 1 kg), and the composition of weight lost was determined by six different models. Total body water (TBW), total body potassium (TBK), and body density, bone mineral content, and fat as determined by dual photon absorptiometry (DPA) were measured while subjects were weight-stable, before and after weight loss. Fat loss was calculated by three two-compartment models (2C-TBW, 2C-TBK, and hydrodensitometry [2C-HD]), one three-compartment model (HD with correction for water content of fat-free mass [FFM], 3C), and one four-compartment model (HD with correction for water and mineral content of FFM, 4C), and was measured directly by DPA. Mean composition of weight loss was similar for all models (mean weight lost as fat: 89% for DPA, 91.5% for 4C, 89% for 3C, 88.6% for 2C-HD, and 87% for 2C-TBW) except 2C-TBK (weight lost as fat, 66%). There was a much wider range of individual values for the 2C-TBW and 2C-TBK models (17% to 138% and 18% to 93%, respectively) than for the multicompartment models (63% to 112%) and DPA (76% to 107%). Almost opposite results were obtained for the same individual when using the 2C-TBK and 2C-TBW models. The discrepancy between these models was due to the inverse relationship between changes in TBW and TBK in the group as a whole (r = .34, NS). In addition, TBK loss was found to be dependent on the initial level of hyperinsulinemia, calculated as the area under the 2-hour oral glucose tolerance curve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406294 TI - Manganese + 2 exhibits dynamic binding to multiple ligands in human plasma. AB - Plasma from fasted adult male subjects was labeled in vitro with 54MnCl2 and then fractionated using several techniques. Molecular sieve chromatography showed that the major 54Mn-containing peak had a very low molecular weight (VLMW), although four other significant peaks, one of which corresponded to the mass of transferrin (Tf), were also observed. The 54Mn content of the Tf peak increased with increasing incubation time in vitro, suggesting the oxidation of Mn+2 to Mn+3 before its association with Tf. This time-dependent effect was verified using affinity chromatography consisting of immobilized anti-Tf. Electrophoretic analyses of plasma yielded equivocal results, indicating a limited value of this method for investigating plasma manganese localization. The above findings are discussed in the context of factors that influence the oxidation and metabolism of Mn2+ in human plasma. PMID- 1406295 TI - Treatment of primary chylomicronemia due to familial hypertriglyceridemia by omega-3 fatty acids. AB - Primary familial forms of chylomicronemia can lead to acute life-threatening complications, especially acute pancreatitis. The main aim of therapy is to avoid this so-called chylomicronemia syndrome. In 12 patients with primary chylomicronemia due to familial hypertriglyceridemia, the addition of 2.16 g omega-3 fatty acids over 4 weeks and 4.32 g for 8 weeks resulted in a decrease of serum triglyceride levels from 1,624 +/- 333 to 894 +/- 241 mg/dL after 12 weeks. Cholesterol and triglyceride levels in the chylomicron fraction were reduced concomitantly, the apolipoprotein B-100/B-48 ratio increased, very--low-density lipoprotein (VLDL) triglycerides, VLDL cholesterol, and total cholesterol levels decreased, and low-density lipoprotein (LDL) cholesterol showed a tendency to increase, but this finding did not reach significance. High-density lipoprotein (HDL) cholesterol levels remained unchanged, as did the levels of apolipoproteins A-I, A-II, and E, and lipoprotein(a). Apolipoprotein B levels decreased significantly. The decrease of triglyceride levels to still-elevated concentrations was accompanied by a substantial decrease in plasma and whole blood viscosity and erythrocyte aggregation, which reached normal values. As in chylomicronemia, complications usually occur at triglyceride levels higher than 1,500 mg/dL; patients can still profit from treatment with omega-3 fatty acids, even though triglyceride levels are still substantially elevated. No clinically relevant side effects occurred, with the exception of the manifestation of diabetes mellitus in one patient, which could be reversed after discontinuation of treatment. PMID- 1406296 TI - Effect of short-term fasting on nocturnal melatonin secretion in obesity. AB - To investigate whether the function of pinealocytes is altered in obesity, nocturnal melatonin (MT) secretion was determined in nine healthy subjects and compared with that of eight obese individuals. Serum MT levels were measured every second hour between 6:00 PM and 8:00 AM, and total nocturnal MT secretion (as reflected by the MT incremental area), MT peak time, and nocturnal urinary MT excretion were determined. None of these parameters differed significantly in the two groups. The obese subjects were reinvestigated after 2 days of complete fasting. This caused a decrease in body weight and basal blood glucose levels of 2.6 +/- 0.2 kg (mean +/- SEM, P less than .001) and 1.5 +/- 0.2 mmol/L (P less than .001), respectively, whereas serum cortisol levels remained unchanged. Short term fasting reduced nocturnal MT secretion, as evidenced by MT incremental areas, which were reduced from 2.01 +/- 0.26 before fasting to 1.64 +/- 0.26 nmol/L.h after fasting (P less than .02). MT secretion peaks were reached simultaneously, and urinary MT excretion values did not change significantly in fasting. To see whether glucose supplementation during short-term fasting would normalize nocturnal MT secretion, we gave an additional seven obese subjects eight small oral doses of glucose (each dose, 0.5 g/kg body weight) at regular intervals during a 2-day fast. Their body weight decreased by 2.8 +/- 0.4 kg (P less than .001), but blood glucose and cortisol concentrations were similar before and after the glucose-supplemented fast, as was the nocturnal MT secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406298 TI - Low and marginal copper intake by postweanling rats: effects on copper status and resistance to carbon tetrachloride hepatotoxicity. AB - Copper feeding studies in rats are generally initiated at weaning. This study examined whether a 6-week feeding of low or marginal Cu levels (0.2 or 2.5 ppm) to rats initially weighing 135 g produced deleterious effects. Controls were fed 8 ppm Cu. Liver Cu-Zn superoxide dismutase activities paralleled Cu intake. Plasma ceruloplasmin activities were very low for both low and marginal Cu consumption. Low but not marginal Cu intake caused a low body weight, high plasma cholesterol level, anemia, cardiac hypertrophy, and a high degree of hepatic plasma membrane injury 24 hours after CCl4 injection (150 microL/kg intraperitoneally [IP]). In summary, low and marginal Cu intakes produced low Cu enzyme activities, while low Cu intake produced pathological symptoms and poor resistance to an oxidative stress. PMID- 1406297 TI - Role of impaired intracellular glucose metabolism in the insulin resistance of aging. AB - The insulin resistance of aging is characterized by both reduced glucose uptake and impaired intracellular glucose metabolism. The aim of this study was to determine whether impaired intracellular glucose metabolism contributes to insulin resistance in the elderly independent of reduced glucose uptake. To address this question, glucose uptake in non-obese elderly males was matched to controls using the glucose clamp technique, and intracellular glucose metabolism was assessed in vivo by indirect calorimetry and in vitro by skeletal muscle biopsy for glycogen synthase activity. When elderly subjects were compared with controls at an equivalent basal glucose uptake of approximately 2.5 mg/kg fat free mass (FFM)/min, muscle glycogen synthase activity was similar (fractional velocity of glycogen synthase at 0.1 mmol/L glucose-6-phosphate [FV0.1], 0.06 +/- 0.1 and 0.07 +/- 0.1), but whole-body rates of glucose oxidation were reduced (1.36 +/- 0.12 v 1.90 +/- 0.11 mg/kg FFM/min, P less than .05). During 40 mU/m2/min hyperinsulinemic clamps at matched rates of glucose uptake (approximately 10.7 mg/kg FFM/min in both groups), glycogen synthase activity was again similar (FV0.1, 0.15 +/- 0.02 and 0.14 +/- 0.02), and glucose oxidation remained reduced in the elderly (4.18 +/- 0.25 v 4.77 +/- 0.17 mg/kg FFM/min, P less than .05). Only during clamps in the maximal range of glucose uptake (approximately 29.5 mg/kg FFM/min) was glucose oxidation between the groups comparable (5.97 +/- 0.50 and 5.75 +/- 0.31 mg/kg FFM/min). Plasma free fatty acid (FFA) concentrations, fat oxidation, and protein oxidation were similar under all study conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406299 TI - Genetically obese rats with (SHR/N-cp) and without diabetes (LA/N-cp) share abnormal islet responses to glucose. AB - To assess the effect of hyperglycemia on the function of islets obtained from obese rats, the behavior of isolated islets from LA/N-corpulent (nondiabetic obese) and SHR/N-corpulent (diabetic obese) male rats was examined and compared. Islets from both genetic models showed a left-shifted glucose dose-response curve for insulin release (concentrations for half-maximal release, 5 to 6 mmol/L v 12 to 13 mmol/L in LA/N lean littermates and 3 mmol/L v 10 mmol/L in lean SHR/N). When insulin release was expressed per unit islet volume, the fourfold to fivefold enlarged islets from both obese diabetic and obese nondiabetic rats showed decreased insulin secretory response in high (16.5 to 28 mmol/L) glucose concentrations, although the decrease was more severe in the diabetic rats. Glucose-stimulated insulin release by islets from both models was relatively resistant to inhibition by 1.2 mmol/L mannoheptulose (eg, 82% +/- 3% inhibition in LA/N lean v 16% +/- 8% in LA/N obese), although nearly complete inhibition was observed with 16 mmol/L mannoheptulose (96% v 85%, NS). Islets of obese diabetic rats were also resistant to the calcium-channel blocker, verapamil, suggesting an abnormal pathway of stimulus-secretion coupling for glucose. Glucose oxidation to carbon dioxide was increased in both obese models at all glucose concentrations when expressed per islet. In data expressed per unit volume, the larger islets from the obese-nondiabetic rats showed a left-shifted dose-response curve with an unchanged maximum rate of glucose oxidation at high (16.5 mmol/L) glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406300 TI - The influence of genetic background on the expression of mutations at the diabetes (db) locus in the mouse. VI: Hepatic malic enzyme activity is associated with diabetes severity. AB - The severity of diabetes produced by the mutation diabetes (db) in the mouse is markedly strain-dependent. When the db mutation is maintained in the C57BL/KsJ (BKs) and DBA/2J strains, severe diabetes is observed, whereas when it is maintained in the C57BL/J (B6) inbred background, a mild, well-compensated diabetes is observed. Our studies on the regulation of malic enzyme activity showed that both the BKs and DBA/2J strains carried the b allele at the malic enzyme regulatory (Modlr) locus and had low enzyme activity, while the B6 strains carried the a allele and had malic enzyme activity two to three times that seen in the BKs and DBA/2J strains. To assess any role of malic enzyme activity in modulating diabetes severity, we produced an F2 generation of diabetic mice using BKs-db/+ and B6-db/+ mice as progenitors. Male diabetic mice of the F2 generation segregated into three groups with respect to diabetes severity. The concordance observed between diabetes severity and malic enzyme activity seen in these three groups suggests a major role for a gene (or a closely linked gene) regulating malic enzyme activity to be responsible for much of the genetic background effects observed with the db mutation in the mouse. PMID- 1406301 TI - Metabolic response to cottage cheese or egg white protein, with or without glucose, in type II diabetic subjects. AB - Test meals with 25 g protein in the form of cottage cheese or egg white were given with or without 50 g glucose to male subjects with mild to moderately severe, untreated, type II diabetes. Water was given as a control meal. The glucose, insulin, C-peptide, alpha amino nitrogen (AAN), glucagon, plasma urea nitrogen (PUN), nonesterified fatty acid (NEFA), and triglyceride area responses were determined using the water meal as a baseline. The glucose area responses following ingestion of cottage cheese or egg white were very small compared with those of the glucose meal, and were not significantly different from one another. The serum insulin area response was 3.6-fold greater following ingestion of cottage cheese compared with egg white (309 v 86 pmol/L.h). The simultaneous ingestion of glucose with cottage cheese or egg white protein decreased the glucose area response to glucose by 11% and 20%, respectively. When either protein was ingested with glucose, the insulin area response was greater than the sum of the individual responses, indicating a synergistic effect (glucose alone, 732 pmol/L.h; glucose with cottage cheese, 1,637 pmol/L.h; glucose with egg white, 1,213 pmol/L.h). The C-peptide area response was similar to the insulin area response. The AAN area response was approximately twofold greater following ingestion of cottage cheese compared with egg white. Following ingestion of glucose, it was negative. When protein was ingested with glucose, the AAN area responses were additive. The glucagon area response was similar following ingestion of cottage cheese or egg white protein. Following glucose ingestion, the glucagon area response was negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406303 TI - DNA structures. Part A. Synthesis and physical analysis of DNA. PMID- 1406302 TI - Epinephrine directly antagonizes insulin-mediated activation of glucose uptake and inhibition of free fatty acid release in forearm tissues. AB - To determine whether the anti-insulin effect of epinephrine is due to a direct antagonism on target tissues or is mediated by indirect mechanisms (systemic substrate and/or hormone changes), insulin and epinephrine were infused intrabrachially in five normal volunteers using the forearm perfusion technique. Insulin (2.5 mU/min) was infused alone for 90 minutes and in combination with epinephrine (25 ng/min) for an additional 90 minutes, so as to increase the local concentrations of these hormones to physiological levels (60 to 75 microU/mL and 200 to 250 pg/mL for insulin and epinephrine, respectively). Systemic plasma glucose and free fatty acids (FFA) concentrations remained stable at their basal values during local hormone infusion. Forearm glucose uptake (FGU) increased in response to insulin alone from 0.8 +/- 0.2 mg.L-1.min-1 to 4.3 +/- 0.8. Addition of epinephrine completely abolished the insulin effect on FGU, which returned to its preinfusion value (0.7 +/- 0.2). Forearm lactate release was slightly increased by insulin alone, but rose markedly on addition of epinephrine (from 5.2 +/- 0.8 mumol.L-1.min-1 to 17 +/- 2; P less than .02). During infusion of insulin alone, forearm FFA release (FFR) decreased significantly from the postabsorptive value of 1.76 +/- 0.25 mumol.L-1.min-1 to 1.05 +/- 0.11 (P less than .01). Epinephrine addition reverted insulin suppression of FFR, which returned to values slightly above baseline (2.06 +/- 0.47 mumol.L-1.min-1; P less than .05 v insulin alone). The data demonstrate that epinephrine is able to antagonize directly insulin action on forearm tissues with respect to both stimulation of glucose uptake and inhibition of FFA mobilization. PMID- 1406304 TI - A-DNA in solution as studied by diverse approaches. PMID- 1406305 TI - Generation and detection of Z-DNA. PMID- 1406306 TI - Supercoiled DNA and cruciform structures. PMID- 1406307 TI - Guanine quartet structures. PMID- 1406308 TI - Purification of synthetic DNA. PMID- 1406309 TI - Crystallographic studies of DNA containing mismatches, modified and unpaired bases. PMID- 1406310 TI - 31P NMR of DNA. PMID- 1406311 TI - Furanose sugar conformations in DNA from NMR coupling constants. PMID- 1406312 TI - Chemical synthesis of deoxyoligonucleotides and deoxyoligonucleotide analogs. PMID- 1406313 TI - Infrared spectroscopy of DNA. PMID- 1406314 TI - Conformation of DNA in vitro and in vivo from laser Raman scattering. PMID- 1406315 TI - Fluorescence resonance energy transfer and nucleic acids. PMID- 1406316 TI - Synthetic oligodeoxynucleotides containing modified bases. PMID- 1406317 TI - Circular dichroism spectroscopy of DNA. PMID- 1406318 TI - Crystallization of DNA. PMID- 1406319 TI - Dynamic light scattering for study of solution conformation and dynamics of superhelical DNA. PMID- 1406320 TI - Modeling DNA structures: molecular mechanics and molecular dynamics. AB - Model building studies may be used to supplement structurally low resolution experimental data with detailed three-dimensional hypothetical atomic models. Because of the strong relation between structure and function in biological molecules such models may give a consistent, integral view of a wealth of experimental data. In most cases such models will predict the outcome of certain experiments. The outcome of these experiments will often either confirm the model may be used for further refinement or even demand a major revision of the model. Coordinates obtained from X-ray fiber diffraction data or in special cases single crystal data may provide the elements for DNA or RNA model building. Local and nonlocal optimization may be used to refine these structures and to evaluate their statistical significance as estimated by a chosen force field. Appreciable progress using nonlocal optimization procedures can only be expected if the dimensionality of the problem can be reduced sufficiently to the relevant degrees of freedom. Taking advantage of structural symmetries may critically improve the convergence while refining the target molecule or its building blocks. Monte Carlo and molecular dynamics methods allow one to calculate averaged quantities. In addition, molecular dynamics provides time evolutions of certain averages. During the simulation of certain physical properties of molecules a huge amount of data will be generated. They will provide many answers, but these answers may not always apply to the original question. So what type of questions will be reliably answered by a force field? Relatively safe answers concern the local geometry of the molecules. If a conformation leads to strong distortions of bond distances or angles or to close van der Waals contacts, this conformation can safely be rejected. Optimizing such unfavorable structures energetically may lead to structures showing how to avoid such distortions. More difficult are energetical questions: which of two conformers is more stable, or what is the free energy of the substrate in the active site? One cannot always be sure that the force field provides the correct answer. Therefore, one should pose only those questions which can be checked experimentally. Because of the many possible answers, the experiment may benefit by starting with a choice proposed by the simulation. The application of this procedure to curved DNA and the DNA four-way junction was successful. PMID- 1406321 TI - Modeling supercoiled DNA. PMID- 1406322 TI - Electron microscopic visualization of DNA and DNA-protein complexes as adjunct to biochemical studies. PMID- 1406323 TI - Scanning tunneling microscopy of nucleic acids. PMID- 1406325 TI - Solution behavior of DNA studied with magnetically induced birefringence. AB - Magnetically induced birefringence can provide useful information on the physical properties of nucleic acids in a variety of forms. The technique is particularly sensitive to structural changes. Difficulties arise with drawing precise structural conclusions principally because of doubts about the relative contributions of the form and intrinsic components to the optical anisotropy. Nevertheless results so far suggest that this might not be a severe limitation. The induced birefringence is very sensitive to cooperative behavior; consequently the transition from an isotropic to a liquid crystalline phase can be followed in detail. Finally the high degree of magnetic orientation often achieved with liquid crystals assists their study with other physical techniques. PMID- 1406324 TI - Cryoelectron microscopy of DNA molecules in solution. PMID- 1406326 TI - Calorimetry: a tool for DNA and ligand-DNA studies. PMID- 1406327 TI - Preparation of psoralen-derivatized oligodeoxyribonucleoside methylphosphonates. PMID- 1406328 TI - DNA structure from A to Z. PMID- 1406329 TI - Artificial life. PMID- 1406330 TI - Automated online transition from the medical record to the psychiatric literature. AB - Psych Topix is a knowledge-based program which guides the clinician from an on line clinical report to a search of the psychiatric literature or of other relevant databases. It provides this guidance by using an outline of key topics in a clinical field to provide "concept-based" links. Each topic is augmented with an activation expression to signal when that topic is potentially relevant to a case, and with database search expressions to allow focused retrieval of information. The bibliographic retrieval component of Psych Topix is currently operational as part of the daily, routine operation of a psychiatric consultation service. The system is also implemented in a demonstration mode to provide retrieval from three additional textual databases. The current Psych Topix system provides a working demonstration of the clinical feasibility of using concept based links to facilitate the focused, automated transition between on-line medical databases. PMID- 1406331 TI - Validation of the AI/RHEUM knowledge base with data from consecutive rheumatological outpatients. AB - The diagnostic accuracy of AI/RHEUM, an experimental expert system for support in the diagnosis of rheumatic diseases, was assessed using a collection of data in a cohort of 1,570 consecutive outpatients of a Dutch rheumatological clinic. Computer diagnoses based on these data and diagnostic predictions made by rheumatologists were compared with reference diagnoses that had been obtained by consensus of rheumatologists after 6-12 months follow-up. Performance of the tested version of the AI/RHEUM knowledge base is presented by various methods. Sensitivity varied between 29% and 100% for different rheumatological diseases. Average sensitivity and specificity for all 26 diagnoses present in the knowledge base were 67% and 98%, respectively. Performance according to the level of confidence indicated that 78% of the "definite", 65% of the "probable", and 33% of the "possible" conclusions made by AI/RHEUM were in agreement with the reference diagnoses. These results approximated the predictions made by rheumatologists after a single, initial examination. The system was less accurate than it had appeared in previous evaluation studies with complex clinical cases. The AI/RHEUM knowledge base needed refining to diagnose early rheumatic complaints. This study further illustrates the need for objective and informative parameters for expressing accuracy of diagnostic support systems. PMID- 1406332 TI - Towards an essential data set: applicability in the domain of maternal health services. AB - There is a need for consensus on the quantity of data that must be available in a computer-based information system of a health care organization. In this paper we take up the issue of defining the data content of an information system and introduce the concept of Essential Data Sets with an explicit methodology which was applied to define a data set for the Maternal Health Services program. A key step in the method was a recognized technique used in systems development process called data modelling, in this case infological modelling, by an interdisciplinary group. A preliminary set of 86 data elements was identified and it provided the foundation for development of an application software for discussion and a real-world testing framework. The acceptability of the data set was tested in a laboratory perspective by retrospective data entry from records of 94 pregnant women registered at a maternal health care center in Sweden. Data from a total of 1,318 prenatal visits, an outcome visit, and a postnatal visit for each woman was entered into a computer using the software, with no loss of information. Thus, in a short-term perspective the acceptability of the data set was demonstrated. The software has since been implemented for pilot prospective studies at sites in India and Sweden. The use of a common data protocol is an essential foundation for patient outcome research, especially as the trend of health care management has changed from a "process of care" orientation to an "outcome of care" orientation. PMID- 1406333 TI - An intelligent computer-assisted instruction system designed for rural health workers in developing countries. AB - This paper describes an intelligent computer-assisted instruction system that was designed for rural health workers in developing countries. This system, called Consult-EAO, includes an expert module and a coaching module. The expert module, which is derived from the knowledge-based decision support system Tropicaid, covers most of medical practice in developing countries. It allows for the creation of outpatient simulations without the help of a teacher. The student may practice his knowledge by solving problems with these simulations. The system gives some initial facts and controls the simulation during the session by guiding the student toward the most efficient decisions. All student answers are analyzed and, if necessary, criticized. The messages are adapted to the situation due to the pedagogical rules of the coaching module. This system runs on PC compatible computer. PMID- 1406334 TI - Dilemmas at a primary health care center: a baseline study for computer-supported cooperative health care work. AB - For the development of computer-supported cooperative health care work this study investigated, based upon activity theory, daily dilemmas encountered by the members of interprofessional primary health care work groups. The entire staff at four Swedish primary health care centers were surveyed, 199 personal interviews being conducted by the Critical Incident Technique. Medical dilemmas were mainly reported by general practitioners and nurses, organizational dilemmas by laboratory staff, nurses' aides, and secretaries, and dilemmas in the patient provider relation by nurses, nurses' aides, and secretaries. Organizational and communication dilemmas reported by nurses, nurses' aides, and secretaries often had their cause outside the control of the individual professional. These dilemmas were often "caused" by other group members (general practitioners or nurses), e.g., by not keeping appointment times or by not sharing information with patients. The implication for computer-supported cooperative health care work is that computer support should be planned on two levels. Collective work activity as a whole should benefit from individual clinical decision support for general practitioners and nurses. However, since most patient communication and organizational problems occurred at group level, group process support is required in these areas. PMID- 1406335 TI - Application of adjusted survival curves to renal transplant data. AB - An important means in the analysis of survival time data is the estimation and graphical representation of survival probabilities. In this paper unifactorial parametric and non-parametric survival curve estimators and two types of adjusted survival curves based on a parametric multifactorial approach are applied to renal transplant data. It is shown that the resulting survival curves can differ substantially. The unifactorial survival curves yield biased results in case of serious disequilibrium in the data. This drawback of the unifactorial methods has been overcome by the use of adjusted survival curves which take possible distortions in the data set into account. The benefits of adjusted survival curves in assessing potentially prognostic factors are elucidated by the application to data from renal transplantation. PMID- 1406336 TI - Maximum likelihood estimation and testing of a poisson regression model. AB - A Poisson regression model is proposed for the analysis of incidence rates presented in a two-way table classified by two categorical variables. It is shown that the likelihood function is the same as that using Glasser's exponential covariate model. An algorithm is given to solve the maximum likelihood estimates of the regression parameters. The model is evaluated via deviance and the method is illustrated with an example. Some extensions of the model are discussed. PMID- 1406337 TI - Adhesion of bacteria on pectin casted films. AB - Pectin and non-pectin degrading bacteria were tested for their ability to adhere to a film casted of low methoxylated pectin (polygalacturonic acid). Klebsiella oxytoca and a newly isolated strain of Escherichia coli adhered to the film, whereas only K. oxytoca was able to utilize pectin as a sole carbon source. Other E. coli strains, containing plasmids with pectinolytic enzymes, did not adhere to the solid pectin film. Therefore, the ability of the bacteria to adhere to the films was not correlated with their ability to degrade pectin. When the solubilization (dissolution) of pectin matrices (tablets) was analysed with and without K. oxytoca, a significant retardation in the dissolution rate was observed in the presence of K. oxytoca, suggesting the formation of a biofilm on the matrix or sedimentation of insoluble pectin salts. PMID- 1406338 TI - Immunomodulating activities of Corynebacterium xerosis cell-wall fractions. AB - Corynebacterium xerosis cell-wall fractions were studied by electron microscopy and analysed for immunomodulating activity. Dramatic splenomegaly occurred following the injection of whole cells or a purified cell-wall fraction (PF), but not with a further purified peptidoglycan (PEP) fraction. Both PF and PEP acted as B-cell mitogens and had adjuvant capabilities comparable to commercial adjuvants. Only the PF fraction enhanced peritoneal natural killer cell (NK) activity, paralleling the splenomegaly response. When spleens from mice injected with PF or PEP were analysed for their abilities to respond to mitogens and for the presence of suppressor cells, reduced mitogenic responses occurred only in PF injected mice during the peak of splenomegaly. Spleens from both PF- and PEP injected mice contained suppressor cell activity which peaked 2 weeks post injection. This activity was primarily directed at B-cell responses to lipopolysaccharide (LPS). C. xerosis cell-wall fractions thus offer great potential as a new immunomodulator. PMID- 1406339 TI - Origins of BCG surface charge: effect of ionic strength and chemical modifications on zeta potential of Mycobacterium bovis BCG, Tice substrain, cells. AB - The zeta potential of washed Tice substrain BCG organisms was measured over a range of ionic strengths from I = 0.005 to 0.1 M. No change in the isoelectric point of 3.4-3.7 was evident. Proteolytic enzymes (trypsin/chymotrypsin, pepsin, papain and pronase) and fluorodinitrobenzene abolished the cationic charge, suggesting that this is substantially due to amino groups associated with protein. Neither hot HCI nor cold trichloroacetic acid affected the charge, indicating that ionic groups are not associated with extractable polysaccharides. Methanolysis, treatment with HF and carbodiimide, and cationic detergent (cetyltrimethylammonium bromide) binding indicated that the negative charge was provided by carboxylic acids, phosphoesters and strong acidic groups, possibly sulphates. Standardless quantitative X-ray microanalysis revealed the presence of phosphorus and sulphur on the surface of actively growing BCG colonies. PMID- 1406340 TI - Isolation of an Enterobacter agglomerans strain with inhibitory activity on Pseudomonas aeruginosa. AB - Antagonism between Enterobacter agglomerans and Pseudomonas aeruginosa was due to an extracellular substance produced by E. agglomerans which accumulates in the culture medium. This substance was also toxic to Escherichia coli and Staphylococcus albus and its MIC for P. aeruginosa ranged between 7.8 and 3.9 micrograms/ml. However, when the extracts from the culture medium were irradiated from 2 h with white light (15 mW/cm2), the MIC was lower (3.9-1.9 micrograms/ml) suggesting that the active substance was a phototoxin. PMID- 1406342 TI - Quantitative determination of Escherichia coli from coliforms and faecal coliforms in sea water. AB - Escherichia coli concentration in sea water was determined by the MUG test after primary growth on membrane filters used to determine total coliforms or faecal coliforms. A good correlation (r = 0.86) was found between E. coli obtained from coliforms versus those from faecal coliforms. Verification procedures showed that all the MUG-positive colonies obtained on both media were E. coli. Evaluation of this data and the literature indicated that this technique for estimation of E. coli in sea water is a useful addition to laboratory procedures without generally increasing the time and the expense of the analysis of recreational water. PMID- 1406341 TI - Mechanism of action of chlorhexidine diacetate and phenoxyethanol singly and in combination against gram-negative bacteria. AB - Chlorhexidine diacetate and the aromatic alcohol, phenoxyethanol in combination had an enhanced bacteriostatic action against Escherichia coli and Pseudomonas aeruginosa strains. Investigations of potassium (K+) ion leakage by means of a potassium electrode and a radioactive method, employing 86Rb, indicated that the combination accelerated the rate of leakage from the cell. Leakage of pentose was also found to be enhanced in the presence of the combination compared with either drug alone. PMID- 1406343 TI - Photosensitizing activity of water- and lipid-soluble phthalocyanines on prokaryotic and eukaryotic microbial cells. AB - The photosensitizing activity of lipophilic zinc-phthalocyanine (Zn-Pc) and its water-soluble sulphonated derivative (Zn-PcS) towards Streptococcus faecium and Candida albicans was studied and correlated with the amount of cell-bound photosensitizer. With both micro-organisms Zn-PcS was more tightly bound in larger amounts than Zn-Pc in the protoplasts of the cytoplasmic membrane. As a consequence, the photoinduced damage in S. faecium initially involved membrane proteins, while DNA was modified only upon prolonged irradiation. For C. albicans only Zn-PcS showed a preferential affinity for the spheroplasts and the decrease in cell survival was not accompanied by detectable modifications of the electrophoretic pattern of membrane proteins. The photoinduced ultrastructural alteration of both micro-organisms suggests damage at membrane level. This would indicate the involvement of different targets in bacteria and yeast for phthalocyanine photosensitization. PMID- 1406344 TI - Cell surface saccharide differences in drug-susceptible and drug-resistant strains of Trichomonas vaginalis. AB - Surface carbohydrates of drug-resistant and drug-susceptible strains of Trichomonas vaginalis were analysed using lectins. The presence of D-GalNAc, D Gal and mannose-like residues was detected in T. vaginalis. Marked differences in exposed surface carbohydrates were documented, e.g. wheat germ agglutinin (WGA) selectively agglutinated the drug-susceptible strain whereas drug-resistant parasites reacted preferentially with concanavalin A (Con A). In drug-resistant, but not in drug-susceptible strains, trypsinization induced the appearance of soybean agglutinin. Binding studies using fluorescein-labelled WGA and Con A essentially confirmed the agglutination experiments. Both the intense cell agglutination and the fluorescent WGA-binding displayed by a drug-susceptible strain, were completely nullified by neuraminidase treatment, suggesting the presence of an exposed sialic acid moiety on the T. vaginalis surface. PMID- 1406345 TI - Structure activity relationships of stendomycin, a lipopeptide antibiotic from Streptomyces. AB - A strain of Streptomyces which produced stendomycin, a lipopeptide antibiotic, was grown in culture media containing various amino acids as nitrogen substrates. The nature of the fatty acid component of stendomycin was dependent on the nature of the amino acid present in the medium, but this did not affect antibiotic activity. Modifications in the peptide moiety resulted in a loss of antifungal activity. PMID- 1406347 TI - DDT can cause pancreas cancer in humans, U-M reports. PMID- 1406348 TI - Most physicians have treated an HIV-positive patient, AMA reports. PMID- 1406349 TI - Balance billing of secondary insurance by Blue Cross participating physicians. PMID- 1406350 TI - Medical inquirer. Physician characteristics. PMID- 1406351 TI - MSMS practice management services expand to meet members' changing needs. PMID- 1406352 TI - Lyme disease in Michigan. An update. PMID- 1406353 TI - Expanding chiropractors' scope of practice not in the best interest of the public. Physicians must convey this message to legislators. PMID- 1406354 TI - MSMS must get tough with the blues. PMID- 1406355 TI - MSMS launches family violence educational campaign. PMID- 1406356 TI - Spouse abuse: the statistics are staggering. PMID- 1406357 TI - Child abuse: physical neglect the most common form. PMID- 1406358 TI - Elder abuse: diagnosis can often be difficult. PMID- 1406360 TI - The administrative burden of third party billing requirements. PMID- 1406359 TI - Study of women IMGs revealing. Many have served as role models, teachers, mentors to women US grads. PMID- 1406361 TI - Michigan's malpractice crisis victimizes many, including residents and postgraduate training programs. PMID- 1406362 TI - Physician-assisted suicide. Societal consensus needed before any legislation can be considered. PMID- 1406363 TI - Molecular cloning and nucleotide sequencing of a novel aminoglycoside 6'-N acetyltransferase gene from an R-plasmid of Salmonella typhimurium S24 isolated in Taiwan. AB - A conjugative aminoglycoside resistance plasmid pST2 has been isolated from Escherichia coli K-12 14R525, which was mated with a clinical isolate of Salmonella typhimurium S24. A novel resistance gene of aminoglycoside 6'-N acetyltransferase[AAC(6')] was cloned from plasmid pST2 on a 1,393 kilobase (kb) of SphI-SalI fragment into vector pACYC184 and pUC18. This novel AAC(6') gene in plasmid pST2 acetylated kanamycin, amikacin, dibekacin, tobramycin, gentamicin, netilmicin, and sisomicin. The complete nucleotide sequence of the novel AAC(6') gene and its neighboring sequences were also determined. Minicell experiments detected only one protein of 24.7 kilodaltons (kDa) translated from an open reading frame of the 618 base pairs (bp) gene. PMID- 1406364 TI - Bacteriostatic and bactericidal activity of antituberculosis drugs against Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare complex and Mycobacterium kansasii in different growth phases. AB - Bacteriostatic and bactericidal activities of rifampicin, isoniazid, streptomycin, enviomycin and ethambutol against Mycobacterium tuberculosis, Mycobacterium avium--M. intracellulare complex and Mycobacterium kansasii were studied in different growth phases. Bacteriostatic activities of the drugs were similar in different growth phases, except isoniazid. M. tuberculosis was much less susceptible to isoniazid in the lag phase than in the log and the stationary phases. In contrast, bactericidal activity was influenced by the growth phase. M. tuberculosis was killed by isoniazid, streptomycin and rifampicin. The bactericidal activity of isoniazid was strongest. The bactericidal activity of isoniazid and streptomycin was most marked in the log phase. M. avium complex and M. kansasii resisted the bactericidal activity, but some strains of M. avium complex were killed by streptomycin and enviomycin, and the activities of these two drugs were most marked in the lag phase. PMID- 1406365 TI - Bactericidal activities of rat defensins and synthetic rabbit defensins on Staphylococci, Klebsiella pneumoniae (Chedid, 277, and 8N3), Pseudomonas aeruginosa (mucoid and nonmucoid strains), Salmonella typhimurium (Ra, Rc, Rd, and Re of LPS mutants) and Escherichia coli. AB - Rat defensins were purified and tested for in vitro bactericidal assay against gram-positive and gram-negative bacteria. Staphylococcus aureus (209P, Cowan I, Smith diffuse and Smith compact) were resistant to defensins, whereas Staphylococcus epidermidis, Staphylococcus saprophyticus, Micrococcus lysodeikticus and Bacillus subtilis were less sensitive. Gram-negative bacteria, such as Pseudomonas aeruginosa (mucoid and K) and Klebsiella pneumoniae (Chedid, 277, and 8N3 which were heavily capsulated, moderately capsulated and noncapsulated, respectively) were all very sensitive to defensins and killed within 20 min. Escherichia coli was moderately sensitive and the rough mutants of lipopolysaccharide (LPS) of Salmonella typhimurium LT2, such as Ra, Rc, Rd, and Re were equally sensitive to defensins, being killed within 40 min. Lysozyme did not show any bactericidal activity except against M. lysodeikticus and B. subtilis, whereas it enhanced the bactericidal activity of defensins against P. aeruginosa, E. coli, and K. pneumoniae and suppressed the killing activity of defensins against S. typhimurium and S. aureus. With regard to the three synthetic rabbit defensins, NP1, NP4, and NP5, NP1 showed strong bactericidal activity against K. pneumoniae 277, comparable to that of rat defensins. Neither NP4 nor NP5 showed any bactericidal activity, while NP5 rather enhanced the bactericidal activity of NP1 against K. pneumoniae 277. PMID- 1406366 TI - Detection of leishmania antigen in kala azar patients using monoclonal antibodies. AB - Twenty-one monoclonal antibodies were produced against promastigote antigens of Leishmania donovani. Five monoclonal antibodies (Hyb.17, 6, 5, 4 and 2) identifying molecules associated with various L. donovani antigenic determinants ranging from 42-116 kDa were selected as 'capture antibodies' and compared with specific anti-leishmania antisera for detection of circulating leishmania antigens in kala azar patients' sera in a competitive-enzyme-linked immunosorbent assay system (ELISA). The anti-leishmania antisera could detect circulating antigen in 30% of kala azar cases while out of the five monoclonals, Hyb.17 could effectively detect circulating leishmania antigen in 85.4%. The efficacy of Hyb.6 was however low (31.7%). The antigens recognized by these monoclonal antibodies in the western blot assay could possibly represent the ones circulating in sera of patients suffering from kala azar. A cocktail of these monoclonal antibodies may be more useful than the conventional polyclonal antisera in detection of circulating antigen for clinical diagnosis of kala azar. PMID- 1406367 TI - Establishment of hybridoma cells with natural killer(NK)-like activity against syngenic tumor cells. AB - The 4D1D4 hybridoma cells were derived from the fusion of spleen cells from BALB/c nude mice with NS-1 mouse myeloma cells. The surface phenotypes of 4D1D4 hybridoma cells were Thy-1.2+, L3T4 (CD4)-, Lyt-2 (CD8)-, Asialo GM1+ and p-55 interleukin-2 (IL-2) receptor (CD25)-. This phenotypic pattern was consistent with the surface phenotype of NK cells. The 4D1D4 cells showed the definite killer activity against a syngenic tumor cell line, RL male-1, but not against an allogenic YAC-1 line. The killer activity of the 4D1D4 cells was not affected by the addition of exogenous IL-2. It was, therefore, suggested that 4D1D4 cells might be representative of resting NK cells with expression of no functional IL-2 receptors. The hybridoma technology might be useful for establishment of the cloned NK cells. PMID- 1406368 TI - A simple purification method of Vibrio cholerae non-O1 hemagglutinin/protease by immunoaffinity column chromatography using a monoclonal antibody. AB - A new simple purification method (I) for Vibrio cholerae non-O1 hemagglutinin/protease (NAG-HA/P) was developed. The method (I) requires only an immunoaffinity column chromatography using a monoclonal antibody against NAG HA/P. The method (I) is much simpler than previously reported purification method (II) (Honda, T. et al, Infection and Immunity 57: 2799-2803, 1989) which required four or more complicated chromatographic procedures. Method (I) also gave an improved recovery rate (about 27%) compared with (II). The molecular weight of NAG-HA/P purified by method (I) was mainly 34 kilodaltons (kDa) with a little of 32 kDa, whereas that of NAG-HA/P purified by (II) was usually 32 kDa. Immunological analysis by the Ouchterlony double gel diffusion test and Western blotting test using polyclonal antibody against 32 kDa protein revealed that the 34 and 32 kDa proteins are immunologically indistinguishable and thus it is supposed that 34 K protein is an isoform or a preform of the 32 K protein. PMID- 1406369 TI - Oligo-2',5'-adenylate synthetase activity in cells persistently infected with human T-lymphotropic virus type I (HTLV-I). AB - Spontaneous production of interferon-gamma (IFN-gamma) was shown in several T lymphoblastoid cell lines persistently infected with human T-lymphotropic virus (HTLV-1). However, the produced IFN-gamma was not always associated with the induction of the antivirus state. The induction of oligo-2',5'-adenylate synthetase (2-5AS) by IFN was studied in five human T-cell lines persistently infected with HTLV-I (MT-1, MT-2, SMT-1, HUT 102 and OKM-2). Four cell lines are able to produce IFN-gamma spontaneously, while the OKM-2 cell line is not. Poor induction of 2-5AS was recognized in three (MT-1, MT-2 and SMT-1) of the four cell lines producing IFN-gamma, though the poor induction was improved after long term cultivation of cells with IFN-alpha. On the contrary, in the OKM-2 cell line, significant activity of the enzyme was induced by IFN-alpha. Induction of 2 5AS was not correlated with cell growth inhibition, but with the antivirus state. Furthermore, an inverse relationship between IFN-gamma production and 2-5AS induction was demonstrated in these cell lines with the exception of HUT 102 cells. PMID- 1406370 TI - Proposal of a new scheme for the serological typing of Enterococcus faecalis strains. AB - No systematic study on serotyping of Enterococcus faecalis has been reported since 1964 when M.E. Sharpe conducted serotyping of group D streptococcus in U.K. So, we attempted to re-evaluate serotyping of E. faecalis. For this purpose, we received 42 Sharpe's strains and first examined for their biochemical characteristics as E. faecalis. Only 9 of the 42 strains were identified as E. faecalis. We raised rabbit antisera against a large number of E. faecalis strains, including the 9 Sharpe's strains, 2 strains obtained from CDC in U.S.A. and 36 strains isolated from patients hospitalized in different cities of Japan. From the results of cross-agglutination tests and absorption tests performed on these antisera using a large number of E. faecalis strains, we were able to classify 21 distinct serotype strains and to prepare 21 monospecific typing antisera by absorption of the antisera to the type strains with appropriate cross agglutinating strains. When 832 E. faecalis strains were serotyped with the 21 typing antisera, 638 strains (76.7%) were typable. Thus, we propose a provisional scheme of 21 distinct serovars in E. faecalis. PMID- 1406371 TI - Impact of Bifidobacterium longum on human fecal microflora. AB - The effects of Bifidobacterium longum feedings for five weeks on the fecal microflora, water contents, pH values, ammonia concentration, and beta glucuronidase activity were investigated in five healthy human volunteers. Although numbers of major bacterial groups of the fecal microflora were not changed by the bifidobacteria feedings, a remarkably decreasing number of lecithinase-negative clostridia was observed. The percentage of lecithinase negative clostridia and bacteroides to the total bacterial numbers isolated were decreased during the feedings and numbers of C. paraputrificum and C. innocuum were reduced. A significant reduction of fecal pH values for the last week of the feeding was observed. Ammonia concentration and beta-glucuronidase activity in the feces during the feedings were significantly lower than those before or after the feedings. The oral supplement of B. longum may be introduced to improve the fecal properties such as fecal ammonia concentration and beta-glucuronidase activity, but not the composition of fecal flora. PMID- 1406372 TI - Cloning and nucleotide sequence analysis of a chloramphenicol acetyltransferase gene from Vibrio anguillarum. AB - The chloramphenicol resistant gene (cat) encoding chloramphenicol acetyltransferase (CAT) in a transferable R plasmid (pJA7324) isolated from the fish pathogen Vibrio anguillarum strain PT24 was cloned into the plasmid vector pUC19. The nucleotide sequence analysis of 1,348 base pair DNA identified an open reading frame encoding a protein of 216 amino acid residues with a calculated molecular mass of 25,471 daltons. The predicted amino acid sequences for this cat gene are 37-69% homologous with other CAT proteins of both Gram-negative and positive bacteria. Colony hybridization performed with a PvuII-BamHI fragment including this cat gene as a probe, revealed that the same or similar chloramphenicol resistance genes existed among V. anguillarum isolates. PMID- 1406373 TI - Focus formation by the human immunodeficiency virus (HIV) in the immobilized MT-4 cell culture and its application to the evaluation of anti-HIV agents. AB - Immunofluorescence studies were performed on the infection of monolayer cultures of immobilized MT-4 cells with human immunodeficiency virus type 1 (HIV-1). By using the anti-viral p24 monoclonal antibody, we could observe formation of foci of p24 antigen-positive cells within 3 to 4 days when the infection was initiated with a relatively small amount of the virus. Frequency of the focus formation was in proportion to the dose of input virus (ranging from 0.001 to 0.1 PFU/cell), which allowed us to apply this phenomenon to the assay of anti-HIV agents as well as to the estimation of relative infectivity of the virus stocks. When antiviral agents were added to the infected cultures, number of foci as well as the size of each focus was reduced in a concentration-dependent manner. The dose required for reducing the number of foci by 50% was calculated to be 6 ng/ml and 8 ng/ml for tunicamycin (TM) and azidothymidine (AZT), respectively. These values are comparable to those obtained by other current assay methods. In addition, focus reduction assay is also useful in searching for such antiviral agents that would inhibit or block the early step of viral replication cycle. PMID- 1406374 TI - An enzyme-linked immunosorbent assay using a chaotropic agent (sodium thiocyanate) for serotype specific reaction between crude dengue viral antigen and anti-dengue mouse antibody. AB - An enzyme-linked immunosorbent assay (ELISA) has been developed to detect serotype specific reaction between crude dengue viral antigen and anti-dengue mouse hyperimmunized antibody under the stringent condition in the presence of a Chaotropic agent, sodium thiocyanate (NaSCN), in the reaction mixture of antigen and antibody. Rapidly sedimenting hemagglutinin (RHA) derived from type 2 dengue virus-infected mosquito cell culture fluid reacted to the antibody for both type 2 and type 3 dengue viruses in the ELISA. In contrast, its reactivity was reduced after the addition of NaSCN in the ELISA. Soluble complement-fixing antigen (SCF) derived from type 2 dengue virus-infected mosquito cell culture fluid reacted serotype specifically to anti-dengue type 2 antibody, and was relatively stable for the NaSCN treatment in the ELISA. Anti-type 2 RHA mouse antibody reacted to both type 1 and type 2 dengue viral antigens and its reactivity was reduced after the addition of NaSCN in the ELISA. Anti-type 2 SCF antibody reacted serotype specifically to type 2 dengue viral antigen with and without NaSCN in the ELISA. PMID- 1406375 TI - A phage in Bartonella bacilliformis. AB - Bacteriophage-like particles were found in Bartonella bacilliformis culture. The particles consisted of head (icosahedral), 40 nm in diameter, and tail, 16 nm in length. PMID- 1406376 TI - Structural similarity of the HLA-DQ region in DQ3 and DQ4 haplotypes and structural diversity of the HLA-DQ region in HLA-DR7 haplotypes. AB - Genomic DNA obtained from a B lymphoblastoid cell line was digested with appropriate restriction endonuclease and hybridized with several probes specific for genes encoding HLA-DQ. Southern hybridization with a DQA1 3'untranslated (UT) region probe showed DQ2-type hybridization pattern in DR7DQ3 haplotype. On the contrary, DQB1 3'UT probe showed DQ3-type pattern in the same haplotype. Gene cloning and DNA sequencing analysis revealed a repetitive sequence, (TG)19, between DQA1 and DQB1 gene in the DR7DQ3 haplotype. These results suggest that a recombination event has occurred near this potential Z-DNA structure in the haplotype, DR7DQ3. The 3'UT region probes of DQA1 and DQB1 genes failed to detect restriction fragment length polymorphism (RFLP) differences between DR4DQ3 and DR4DQ4 haplotypes in this experiment, suggesting that the gene structure between DQA1 and DQB1 is conserved in these haplotypes. PMID- 1406377 TI - Comparison of immunological effects of cholera toxin on autoimmune MRL/lpr and BXSB mice. AB - MRL/lpr and BXSB mice were treated weekly or biweekly with cholera toxin (CT) in intravenous dose of 2 micrograms/mouse. CT treatment notably alleviated proteinuria in MRL/lpr mice, but did not influence the course of lupus nephritis in BXSB male mice. Flow cytometric analysis showed that anomalous B220+ T cells in spleen and thymus were reduced in CT-treated MRL/lpr mice while no significant change in lymphocyte populations was induced in BXSB male mice by this treatment. The suppressive effect of CT treatment on Con A response and the augmentative action on LPS response were observed in MRL/lpr mice. The latter may reflect increased B cells in relative number in the peripheral lymphoid organs. Mitogenic responses in CT-treated BXSB male mice remained unchanged in comparison with those of untreated group. Increased production of IL-6 by spleen cells was demonstrated in MRL/lpr mice treated with CT while in BXSB mice the level of IL-6 was not changed by the treatment with CT. Production of IFN gamma was suppressed by CT treatment in both strains of mice. This may be attributed to the inhibitory effect of CT on IFN gamma-producing Th1 cells as reported previously (Munoz et al, J. Exp. Med. 172: 95-103, 1990). However, CT treatment did not inhibit anti DNA antibody production in BXSB mice, whereas the autoantibodies were markedly decreased in MRL/lpr mice treated with CT. PMID- 1406378 TI - Further evaluation of the pregnancy-linked down-regulation of the paternal antigen-specific splenic cytotoxic T lymphocyte activity in allogeneically pregnant mice. AB - Cytotoxic T lymphocyte (CTL) activity directed against paternal alloantigen was examined in allogeneically pregnant mice using various allogeneic combinations. The spleen cells from pregnant C57BL/6 (H-2b) mice mated with BALB/c (H-2d) male mice generated less anti-H-2d CTL after in vitro sensitization than those from unpregnant or syngeneically mated C57BL/6 mice. Different allogeneic combinations including the incompatibility at only D region of H-2 or minor histocompatibility loci were effective for downregulating the anti-paternal CTL activity in pregnancy. The downregulation of anti-paternal CTL activity induced by allogeneic pregnancy occurred at day 10 to day 18 of pregnancy, most extensively at day 14. The allogeneic pregnancy also downregulated the allogeneic CTL activities that had been amplified by injecting alloantigens before mating. PMID- 1406379 TI - Extracellular localization of a nonfimbrial hemagglutinin of Yersinia pseudotuberculosis. AB - A nonfimbrial hemagglutinin (HA) of Yersinia pseudotuberculosis was observed by immunoelectron microscopy using monospecific HA antiserum and protein A-gold conjugate. The HA, an amorphous but morphologically identifiable entity, was located in a region distal to or detached from the outer edge of bacteria. PMID- 1406380 TI - [Current methods for the laboratory diagnosis of campylobacteriosis]. AB - An analytical review of recent publications of home and foreign authors on the problem of laboratory diagnosis of campylobacteriosis is presented. The commercial nutrient media, methods of creation of the microaerophilic conditions for cultivation of campylobacter are presented. The filtration method is preferable for isolation of these agents from the studied material highly contaminated by accompanying microflora. A special attention is paid to immunodiagnosis of campylobacteriosis: agglutination reaction, coagglutination reaction, passive hemagglutination reaction, immunoenzyme and radioimmune analyses. Seroepidemiological examination of the staff at one of meat-packing factories in the Republic carried out by the method of indirect immunoenzyme analysis has revealed high levels of anticampylobacteriosis antibodies in 17.9% of examinees. The promising trends in perfection of the methods for laboratory diagnosis of campylobacteriosis are outlined. PMID- 1406382 TI - [The effect of physicochemical factors on the activity of DNA-dependent DNA polymerases in Acholeplasma laidlawii PG-8]. AB - The biological and physico-chemical properties of DNA-dependent DNA-polymerases of Acholeplasma laidlawii PG-8 have been studied. The optimal parameters of maximal enzymatic activity are determined. It is stated that N-ethylmaleimide in concentration of 1 mM activated DNA-polymerase I by 52%, whereas DNA-polymerase II with reagent concentration of 0.5 mM demonstrated the peak of activity exceeding the control only by 10%. Spermidine in concentration of 1.5 mM for the first form of DNA-polymerase and 0.15 mM-for the second one increased the ability of both forms of polymerases to synthesize DNA by 10%. Aphidicolin added to the reaction medium up to concentration of 10 mg/ml decreased activity of forms I and II of enzymes by 83 and 68%, respectively. The presence of 0.6 mM of EDTA in the medium also negatively affected the activity of polymerases inhibiting it by 83% in form I and by 77%-in form II. PMID- 1406381 TI - [The intestinal microflora of persons subjected to a radiation lesion]. AB - The content of large intestine has been studied in persons exposed to radiation injury in consequence of the accident at the Chernobyl Atomic Power Plant. It is stated that bifidobacteria (10(7)-10(10) cells in 1 g of feces) prevailed (as in healthy people), Bifidobacterium indicum being a dominating species. Amount of lactic-acid bacteria in 1 g of defecations of examined patients was within the range of 10(6)-10(9) cells and in certain persons it reached 10(10) cells (primarily fecal Enterococci). A considerable amount of patients with acute radiation sickness of the 3d degree had in their intestine 10(9)/g of lactic-acid bacteria, Lactobacillus casei and L. plantarum prevailing there. The frequency of yeast isolation from defecations of patients constituted 83%, while the number of cells in 1 g of feces--from 10 to 10(4). Yeast of the Candida genus, mainly Candida parapsilosis, prevailed. The species composition of isolated microorganisms has no substantial differences from microcenosis of healthy people. The content of intestine of persons suffered from radiation is characterized only by greater amount of lactic-acid bacteria and enterococci as compared with healthy adults. PMID- 1406383 TI - [The RNAse activity in mycoplasmas of different taxonomic positions]. AB - Dynamics of the RNAase accumulation in cells and culture fluid of strains of Acholeplasma and Mycoplasma genera has been studied. In certain strains of two genera of mollicutes some differences in dynamics of RNAase formation by them are determined. PMID- 1406384 TI - [The effect of physicochemical factors on the growth of Pseudomonas putida BS-2 on a medium with diethylene glycol]. AB - The physicochemical factors of medium have been studied for their effect on the physiological indices of growth of Pseudomonas putida BS-2 culture utilizing diethylenglycol as the only source of carbon. Action of the supraoptimal temperature on the growth process of P. putida BS-2 is accompanied by a decrease (more than twice) in economic coefficient of substrate and specific growth rate as compared with their maximal values. Dependences of specific growth rate of P. putida BS-2 in the medium with diethylenglycol on the presence of NaCl in it within the range of its concentrations from 0 to 4% and methanol in the concentration range of 0-20 g/l follow the noncompetitive inhibition equation. When NaCl concentration in the medium is more than 4%, complete separation of constructive and energy metabolism processes is observed. PMID- 1406385 TI - [The immunological shifts in the blood sera of persons inoculated with influenza vaccines]. AB - The dynamics of antihemagglutinin content in blood serum of students inoculated with different types of influenza virus vaccines has been traced out in the process of long-term observation. It is shown that this dynamics depends on the type of used vaccines, method of their introduction and epidemiological situation. It is stated that in the process of annual vaccination the highest titres of antihemagglutinins are observed in twice inoculated patients; after the third vaccination these titres decrease and after four-fold vaccination--they increase again. PMID- 1406386 TI - [Bacteria of the genus Aeromonas and their role in aquaculture]. AB - Bacteria of genus Aeromonas are constant components of microbiota of fresh reservoirs where they, together with other microorganisms, play the part of natural biofilter and promote water self-purification. They are necessarily present in normal microflora of hydrobionts inhabiting fresh reservoirs. The greatest attention is paid by the researchers to Aeromonas and biotrophs in connection with epizootics in aquaculture which have become more frequent, in particular, under fish breeding. That is why the review is, to more extent, concerned in the works of this trend made by the foreign and home researchers for the last decade. PMID- 1406387 TI - The value of general practice. PMID- 1406388 TI - The excimer laser in Australia. PMID- 1406389 TI - Steroid-sparing agents in the treatment of asthma. PMID- 1406390 TI - Therapeutic goods and malaria. PMID- 1406391 TI - Community prevalence survey of children's blood lead levels and environmental lead contamination in inner Sydney. AB - OBJECTIVE: To determine the distribution of blood lead levels in preschool children in inner Sydney and identify possible sources of environmental lead. DESIGN: Cross sectional community based prevalence survey of children and the houses in which they live, and a survey of volunteer children. SETTING: Mort Bay and Summer Hill, residential localities in inner Sydney. PARTICIPANTS: Ninety five children aged 9-48 months able to be identified in a defined geographic area and 63 children aged 9-48 months volunteered by their parents. OUTCOME MEASURES: Concentrations of lead in venous blood of all children and in samples from the home environment of Mort Bay children. RESULTS: Four of the children (2.5%) had blood lead levels > or = 1.21 mumol/L (25 micrograms/dL, the current Australian threshold of concern), 27 (17.1%) had levels > or = 0.72 mumol/L (15 micrograms/dL, the new US threshold for individual intervention) and 80 (50.6%) had levels > or = 0.48 mumol/L (10 micrograms/dL, the new US threshold for community intervention). Blood lead concentrations were significantly correlated with concentrations of lead in "sink" soil (r = 0.555, P = 0.026), play area soil (r = 0.492, P = 0.016) and dust from vacuum cleaners (r = 0.428, P = 0.05), and with age of child (r = -0.182, P = 0.023). The presence of the child during house renovation was a strong predictor of having a blood lead level above 0.72 mumol/L (15 micrograms/dL) (odds ratio, 4.6; 95% confidence interval, 1.8-11.7, P = 0.001). CONCLUSIONS: Lead in soil and in household dust in older areas of Sydney is likely to represent a significant health hazard to young children. Many thousands of children may be affected in Sydney and other Australian cities. There is an urgent need for expanded prevalence surveys, public education and the development of strategies for the abatement of lead in urban environments. PMID- 1406392 TI - The use of portable blood glucose monitors by trained lay operators. AB - OBJECTIVE: To evaluate the use of Reflolux II blood glucose reflectance meters by trained lay operators in a community survey. DESIGN: A random household survey involving assessment of participants' blood glucose levels by Reflolux II. For a random subsample of participants an additional sample of blood was placed onto filter paper strips and stored for later examination and assay. SETTING: The survey was conducted in the Newcastle and Lake Macquarie areas of New South Wales. PARTICIPANTS: Of the 1275 participants 15 years and over, 1229 consented to have their blood glucose assessed and 163 of these also had blood stored on filter paper strips. Data were collected by 25 interviewers. MAIN OUTCOME MEASURES: Application of blood spots to filter paper assessed the interviewers' capacity to collect samples of minimal acceptability for Reflolux II operation. Samples were considered adequate if they covered at least a 6 mm soaked disk and there was no evidence that they had been smeared or applied from both sides of the paper. The Reflolux II readings obtained by the interviewers were compared with the blood glucose values from assay of the filter paper samples. RESULTS: Only 63% of the 163 samples collected on filter paper were of acceptable quality for adequate Reflolux II operation. The overall correlation between Reflolux II blood glucose values and those determined from the blood collected on filter paper was good (r = 0.893). However, three of the eight interviewers who had five or more readings for comparison achieved correlation coefficients of < r = 0.20. Of the survey participants identified as having elevated blood glucose levels (> 8 mmol/L) by the filter paper assay, 58% (7 of 12) were not detected by the lay operated reflectance meters. Twenty-two per cent of the individuals assessed by the reflectance meter, compared with 0.5% of a population sample surveyed by the National Heart Foundation, had blood glucose values of less than 3.5 mmol/L. CONCLUSION: It would appear that there may be a considerable error rate in blood glucose values obtained by lay operators using reflectance meters, resulting in underestimation of blood glucose levels. The findings have implications for community awareness programs for diabetes and highlight the need for careful training and monitoring of lay operators in their obtaining of finger-prick blood samples and their use of reflectance meters. PMID- 1406393 TI - Regional variation in coronary mortality within Tasmania. AB - OBJECTIVE: To measure regional rates of mortality from ischaemic heart disease (IHD) within Tasmania and to analyse factors associated with regional differences. DESIGN: Descriptive epidemiological study. SETTING: Community-based study. SUBJECTS: Male residents of Tasmania aged 30-69 years dying from IHD between 1986 and 1989. MAIN OUTCOME MEASURES: Coronary death as coded by the Australian Bureau of Statistics and place of death validated by hospital and community data. RESULTS: This study identifies substantial differences in coronary death rates among the three Health Regions of Tasmania. These differences are real and are not caused by variations in diagnostic or coding practices between regions. The two northern Health Regions, which represent approximately 52% of the total population, account for 98% of the excess mortality from IHD in Tasmania compared with the national rate. More detailed analysis of these differences suggests that variation in the number of deaths occurring in hospital contributes significantly to the regional differences in death rate from IHD. CONCLUSION: Rates of coronary mortality in Tasmania have been significantly higher than in all other Australian States for much of the past decade because of a higher death rate within the population of the northern half of Tasmania. Differences in mortality rates between regions in Tasmania provide a focus for further study into the causes of the unacceptably high rates of death from IHD in Tasmania and underline the need for the funding of a coronary register in Tasmania. PMID- 1406394 TI - The importance of hypertension in the aetiology of infarctive and haemorrhagic stroke. The Lower Hunter Stroke Study. AB - OBJECTIVE: To determine the importance of hypertension in the aetiology of infarctive and haemorrhagic stroke in persons aged 35-69 years. DESIGN: A population-based case-control study. SETTING: Lower Hunter Region community. SUBJECTS: One hundred and ninety patients with a first stroke were identified from a register, including all hospital admissions and death certificates in the Region, and compared with 496 control subjects obtained from a random population sample of the same community. MAIN OUTCOME MEASURE: First event of stroke (fatal or non-fatal). RESULTS: Twenty-seven per cent of those with a haemorrhagic stroke, compared with 2% of those with infarctive stroke, died before hospital admission; the in-hospital mortality was 15% and 9%, respectively. Twenty-one per cent of control subjects, compared with 51% of those with stroke, were currently receiving treatment for hypertension. By logistic regression analysis the odds ratio for receiving current treatment for hypertension in those with haemorrhagic stroke was 5.5 (95% confidence interval [CI], 2.36-12.8), compared with 2.53 (95% CI, 1.48-4.34) in those with infarctive stroke. Other differences between haemorrhagic and infarctive stroke included no excess risk in men for haemorrhagic stroke but an odds ratio of 3.51 (95% CI, 1.83-6.74) for infarctive stroke; and a steep risk gradient for obesity in haemorrhagic but not in infarctive stroke. Cigarette smoking carried a non-significant odds ratio of around 1.5, with no difference between stroke type. Among those who had ever been told that they had hypertension, 75% and 71% of patients with infarctive stroke and haemorrhagic stroke, respectively, and 61% of control subjects, were currently receiving treatment for hypertension. In those stroke patients who were currently being treated for hypertension, 63% had a pre-admission diastolic blood pressure of 90 mmHg or more. The mean diastolic blood pressure levels on admission were 10 mmHg higher than the latest recorded pre-hospital measurements and fell to 10 mmHg lower than the levels recorded before hospital admission by the time of discharge. CONCLUSION: Hypertension is important in the aetiology of both infarctive and haemorrhagic strokes, although it may be more important in haemorrhagic stroke, and there appear to be other aetiological differences between stroke types. Most of the patients with a history of hypertension were currently receiving treatment for hypertension, although blood pressure control before admission was not optimal. PMID- 1406396 TI - GPs can help patients to stop smoking. PMID- 1406395 TI - Successful management of primary hypercholesterolaemia with simvastatin and low dose colestipol. AB - OBJECTIVE: To examine whether a small dose of bile acid sequestrant used in combination with a hydroxymethylglutaryl coenzyme A reductase inhibitor is more effective in reducing serum and low-density lipoprotein (LDL) cholesterol levels than inhibitor used alone. DESIGN: A randomised, double-blind study. SETTING: Subjects receiving tertiary care at a hospital lipid clinic. PATIENTS: Subjects with severe primary hypercholesterolaemia (types IIa and IIb), already stabilised on a cholesterol-lowering diet, with serum cholesterol levels of 7.0 mmol/L or more and triglyceride levels of 6.0 mmol/L or less. Sixty-four subjects were randomly assigned to the treatment groups; three withdrew before any outcome observations; 61 completed the trial and their results were analysed. INTERVENTIONS: Subjects were randomly assigned to receive either colestipol placebo or colestipol 5 g or 10 g each morning in fixed dosage for 18 weeks. They simultaneously received incremental doses of simvastatin: placebo for six weeks, then 20 mg/night for six weeks, then 40 mg/night for a final six weeks. MAIN OUTCOME MEASURES: Lipids, lipoproteins, and haematological and biochemical safety parameters were measured at the end of each treatment period. Adverse events were monitored. RESULTS: Respective maximum reductions (95% confidence intervals) in serum cholesterol, LDL cholesterol and apolipoprotein B (apo-B) values in subjects taking combination therapy were 41% (38%-45%), 50% (46%-53%) and 43% (39%-46%), compared with lesser reductions of 32% (26%-37%), 38% (31%-45%) and 37% (32%-41%) in those taking simvastatin monotherapy. The percentage changes in LDL cholesterol with combination therapy were independent of baseline cholesterol level or lipid phenotype. Combination therapy reduced serum triglyceride levels by up to 24% (15%-32%) and increased high-density lipoprotein (HDL) cholesterol levels by up to 9% (3%-15%). Three subjects withdrew within a few weeks because of severe gastrointestinal side effects related to colestipol; 19 experienced milder gastrointestinal side effects, 15 were taking combination therapy. CONCLUSIONS: A combination of low-dose colestipol and simvastatin was found to be more effective in reducing serum and LDL cholesterol than simvastatin used alone. Such combination therapy offers the possibility of improved cholesterol lowering without the need for full dosage of either drug. PMID- 1406397 TI - Anterior cruciate ligament injuries. Clues for diagnosis. PMID- 1406398 TI - ARGPUs--academic rural general practice units. PMID- 1406399 TI - Adverse reaction to a Chinese herbal remedy. AB - OBJECTIVE: To report a multisystem illness in a patient after ingestion of Chinese herbal medicines, together with an analysis of the herbal medicine and to alert physicians to the growing clinical importance of adverse reactions to herbal remedies. CLINICAL FEATURES: A 61-year-old Chinese Vietnamese man with a history of atrial fibrillation and left cerebral hemisphere infarction three months previously presented after a three-day illness with acute hepatorenal failure, multiple pulmonary emboli, peripheral arterial thromboembolism and laboratory features of consumptive coagulopathy. For three days before presentation, he drank a daily infusion of herbal medicine. INTERVENTION: Intensive supportive medical care including haemodiafiltration resulted in recovery of renal function, liver function and return of coagulation parameters to normal over a one-month period. Toxicological analysis of an infusion prepared from a sample of the patient's herbal medicine revealed the potentially toxic compounds benzaldehyde, cinnamoyl alcohol and ephedrine. CONCLUSION: The ingestion of herbal medicine caused or contributed to the patient's illness. PMID- 1406400 TI - Behavioural changes due to pontine and extrapontine myelinolysis. AB - OBJECTIVE: To report a case of central and extrapontine myelinolysis with unusual behavioural manifestations that developed after slow (not more than 0.5 mmol sodium per litre per hour) correction of hyponatraemia. CLINICAL FEATURES: A 51 year-old Caucasian woman with hyponatraemia caused by psychogenic polydipsia experienced a delayed onset of behavioural changes with some ataxia, but no pyramidal signs, after correction of the hyponatraemia. INTERVENTION AND OUTCOME: The hyponatraemia was corrected with a combination of hypertonic saline and fluid restriction at the currently recommended rate of not more than 0.5 mmol of sodium per litre per hour. CONCLUSION: Central and extrapontine myelinolysis may develop after slow correction of hyponatraemia. Behavioural manifestations may be the most prominent clinical feature. PMID- 1406401 TI - Will computers replace or complement the diabetes educator? AB - Computer programs are playing an increasingly important role in the management of diabetes and fall into various categories. Instructional programs are used to teach patients about diabetes. They cover the principles of blood glucose monitoring, diet, exercise, foot care and so on. Statistical and graphical analysis programs are used in diabetes clinics to help the physician, diabetes educator and patient detect patterns and trends in the patient's home blood glucose readings. Hand-held insulin dosage computers have been used by patients to advise them on insulin dosage adjustment on a day-to-day basis. The diabetes simulator we have recently developed allows patients to practise, and gain experience with insulin dosage adjustment; the patient decides on alterations to insulin dose, diet or the amount of exercise and the computer program demonstrates the resulting effect on blood glucose levels. Overall, computers complement and enhance, rather than replace the functions of the diabetes educator. PMID- 1406402 TI - CME--the government, universities and colleges. PMID- 1406403 TI - News in diabetes. PMID- 1406404 TI - Ascaris lumbricoides and peak expiratory flow rates in children aged 5-15 years. PMID- 1406405 TI - Transfusion-induced malaria in Victoria. PMID- 1406406 TI - Yet another manifestation of degenerative changes? PMID- 1406407 TI - AIDS--beyond education. PMID- 1406408 TI - AIDS--beyond education. PMID- 1406409 TI - General practice as a scientific discipline. PMID- 1406410 TI - Whiplash in Australia: illness or injury? PMID- 1406411 TI - Nurse practitioners in general practice. PMID- 1406412 TI - Costs and benefits of the use of commercial market research approaches in large scale surveys. PMID- 1406413 TI - Pancreas/islet cell transplantation: a medical and ethical dilemma. PMID- 1406414 TI - Laparoscopic surgery: some unresolved issues. PMID- 1406415 TI - A fresh look at IUDs: advancing contraceptive choices. PMID- 1406417 TI - Pulmonary angiography in a non-teaching hospital over a 12-year period. AB - OBJECTIVE: To report the safety of pulmonary angiography in a non-teaching hospital and discuss the place of this investigation in the diagnosis of pulmonary embolism. DESIGN AND SETTING: A retrospective review of all patients undergoing pulmonary angiography over a 12-year period, November 1979 to October 1991, at Dandenong Hospital, Melbourne. A protocol was established whereby each procedure was performed with the assistance of staff and equipment from the intensive care unit to provide haemodynamic monitoring and measurement of pulmonary artery pressures. PATIENTS: During the review period 114 patients underwent pulmonary angiography, most (108) for suspected pulmonary embolism. RESULTS: One hundred and fifteen pulmonary angiograms were performed, and no deaths related to the procedure occurred. Complications included perforation of the right atrium in three patients, with no sequelae. Cardiac arrhythmias were common but self-limiting. CONCLUSION: In our series, pulmonary angiography was a safe procedure if undertaken with the appropriate monitoring measures. A protocol which includes the participation of the intensive care unit has proved helpful. In addition, it was found that clinical symptoms and signs were unreliable and in 24 patients who also had ventilation-perfusion (V/Q) scans, only seven scans were accurate. A review of the literature indicates that V/Q scans lack specificity and that pulmonary angiography may be performed safely. The latter investigation should be more frequently performed. PMID- 1406416 TI - Treatment of primary hypercholesterolaemia with pravastatin: efficacy and safety over three years. AB - OBJECTIVE: To assess the efficacy, safety and tolerability of pravastatin over three years of treatment. DESIGN: An open, multicentre randomised study. SETTING: Subjects receiving tertiary care at three hospital lipid clinics. PATIENTS: Subjects with primary hypercholesterolaemia (type IIa) or combined hyperlipidaemia (type IIb), already stabilised on a cholesterol-lowering diet, with low density lipoprotein (LDL) cholesterol levels of greater than 4.7 mmol/L and triglyceride levels of less than 4.5 mmol/L. Sixty-one subjects were randomly assigned to the treatment groups: 60 completed 12 weeks and 46 completed 30-36 months of treatment. INTERVENTIONS: Subjects were randomly assigned to receive either pravastatin 20 mg/day, pravastatin 40 mg/day or cholestyramine 16 g/day for a period of 12 weeks. Subsequently, dose titration of pravastatin up to 40 mg/day was permitted, if required, and all groups received supplementary therapy with other lipid-lowering drugs. MAIN OUTCOME MEASURES: Lipids, lipoproteins, haematological and biochemical safety parameters were measured at regular intervals. Adverse events were monitored. RESULTS: There were significant reductions in total and LDL cholesterol levels with all treatments over 12 weeks (P < 0.001). The mean reductions (+/- SD) in LDL cholesterol were 26% +/- 14% in the group taking pravastatin 20 mg/day (n = 21), 30% +/- 8% in the group taking pravastatin 40 mg/day (n = 21) and 34% +/- 13% in the group taking resin (n = 18). The percentage changes in LDL cholesterol were independent of age, baseline cholesterol level or lipid phenotype. High density lipoprotein (HDL) cholesterol levels were significantly increased, by 8%-18% with all treatments (P < 0.001). Triglyceride levels were reduced by high-dose pravastatin only (7% +/- 29%), but were found to increase with resin (45% +/- 63%). During long-term treatment over 36 months, still greater reductions in total and LDL cholesterol were found in patients taking pravastatin (n = 35), but not in those taking resin (n = 11). There was an apparent decrease in effect beyond 18 months in both groups, possibly related to reduced compliance with diet or cholestyramine intake. Eight subjects allocated to pravastatin and seven allocated to resin withdrew (one and two subjects respectively because of drug-induced adverse events). Adverse events during 12 weeks' monotherapy with pravastatin included central nervous system (CNS) symptoms (12%), gastrointestinal (GIT) symptoms (7%) and an acute hepatitic reaction (one subject). Of those in the resin therapy group, 22% developed GIT symptoms. Myalgia occurred in three subjects using a combination of pravastatin and clofibrate, but this resolved fully upon clofibrate withdrawal. CONCLUSIONS: Pravastatin was found to be a relatively effective, safe and well tolerated lipid lowering drug. Still greater LDL reduction was achieved with pravastatin combination therapy and this was essentially maintained over three years. PMID- 1406418 TI - Exposure to blood borne infections in health care workers. AB - OBJECTIVE: To determine the incidence and nature of occupational exposures to blood and body fluids in health care workers. DESIGN: 332 reports of occupational exposure were analysed and are presented. SETTING: A major teaching hospital. PARTICIPANTS: All staff at Royal Perth Hospital who reported an occupational exposure to blood or body fluids to the Department of Clinical Immunology between 1 January 1990 and 31 August 1991. OUTCOME MEASURES: The rate of reported occupational exposure according to staff category, nature of exposure, HIV status of source patient, activity at the time of exposure and compliance with infection control measures. RESULTS: 332 reports from 323 health care workers were received, giving an overall incidence of 6.1 per 100 full time equivalent (FTE) years. Nursing staff (9.4/100 FTE years) and medical staff (9.0/100 FTE years) reported exposure more frequently than housekeeping staff (2.5/100 FTE years) or paramedical staff (2.3/100 FTE years) (P < 0.001). The rate of exposure to HIV antibody positive patients was only 0.24/100 FTE years. Needlestick or other blood contaminated sharps injuries accounted for 83.4% (277/332) of reports and failure to observe universal precautions for 34.0% of reports. Insertion and operation of parenteral lines (24%) and performing operations (15.4%) were the activities most often associated with occupational exposure. No occupationally acquired infections were observed. Despite the immediate availability of zidovudine, acceptance by health care workers with high risk occupational exposure was low (18.8%). CONCLUSIONS: Occupational exposure to blood and body fluids is common among health care workers but most exposures confer a low risk of blood borne infection. The introduction of an occupational exposure assessment program has many benefits, including optimal management of injuries and acquisition of data on infection control measures, and may protect health care institutions from false claims for compensation. PMID- 1406419 TI - Mycobacterium marinum infection: epidemiology and presentation in Queensland 1971 1990. AB - OBJECTIVE: Evaluation of the clinical and epidemiological features of Mycobacterium marinum infection in Queensland. DESIGN: Laboratory identification and in-vitro susceptibility tests of 29 isolates from the Queensland Health Department Tuberculosis Reference Laboratory were retrospectively gathered and followed up by contacting referring practitioners and obtaining clinical details of patients involved. SUBJECTS: 29 patients from whom M. marinum was isolated, with a male:female ratio of 3.1:1, and a mean age of 47.4 years. RESULTS: Of 26 patients for whom adequate information was available, 12 had evidence of involvement of deep tissues (including two cases of arthritis) and five suffered sporotrichoid spread of infection. The delay between onset of symptoms and consultation with a medical practitioner was five months (range, two weeks to two years), with a further mean delay to definitive diagnosis of 4.4 weeks. Cure was apparent in 22 of 23 cases. Chemotherapy alone was adequate in 11 cases, as was surgical intervention in three, while a combination approach was successful in eight cases. Trimethoprim/sulfamethoxazole was successful in seven of nine cases and combination rifampicin and ethambutol in six of seven. Tetracyclines were employed as single-agent therapy in nine patients and were effective in seven. CONCLUSIONS: Synovitis was a common presenting feature of M. marinum infection in Queensland patients. Occupational and recreational exposure to salt or fresh water was common, and although this history was available to practitioners a mean delay to definitive diagnosis of 4.4 weeks still occurred. The data suggest that chemotherapy alone is often adequate, even with deep tissue involvement. Combinations of conventional antimycobacterial drugs may be the therapy of choice, especially for serious infections, although success was recorded with trimethoprim/sulfamethoxazole alone. PMID- 1406420 TI - The economic impact of chronic fatigue syndrome. AB - OBJECTIVE: To estimate the economic impact of chronic fatigue syndrome (CFS) on the individual, the government, and the community. DESIGN: The financial burden produced by CFS was studied by calculating the direct and indirect costs arising from the disorder. Data regarding use of health resources, income and employment were obtained by questionnaire from patients with CFS. In addition, aggregate Medicare data on the incidence and fees charged for each Schedule item for these patients was obtained. SETTING: The Richmond Valley, New South Wales. PARTICIPANTS: Forty-two patients with CFS identified in our population-based prevalence study. RESULTS: The conservative estimate of the per annum costs of CFS in the Richmond Valley, with a prevalence of 37.1 cases per 100,000, was $396,000. If extrapolated to the Australian population, we estimate CFS would generate an annual cost of at least $59 million. CONCLUSION: This disorder constitutes a large but neglected area of health resource utilisation and economic burden. PMID- 1406421 TI - Modern methods of searching the medical literature. AB - OBJECTIVE: To review the methods of electronic retrieval of biomedical journal articles; to demonstrate CD-ROM and online searching techniques; and to compare major biomedical databases. DESIGN: A CD-ROM MEDLINE search was made by a medical practitioner, with the assistance of an experienced librarian. An online MEDLINE/Excerpta Medica search was made by the same medical practitioner after completion of a two-day course in search techniques. The search example covered the period 1983 to 1992, and the topic was "whether steroid use for asthma/airways disease leads to osteoporosis". OUTCOMES: Search duration, article yield and search cost were assessed. RESULTS: The CD-ROM MEDLINE literature search took 60 minutes to find 31 articles (43% of the possible articles). This compared with an online search to the Bibliographic Retrieval Services database in Chicago, which produced the same articles when MEDLINE was searched (but took only 16 minutes) and which also found 47 articles (with an overlap of only seven) when Excerpta Medica was searched. We estimated that the combined MEDLINE and Excerpta Medica search detected 93% of all known relevant articles, based upon an assumed gold standard. CONCLUSIONS: Online searching is a fast and powerful alternative to CD-ROM searching. Formal training is necessary for quick and cheap reference finding. Other benefits such as direct transfer from online searching to your own computer bibliography database make online searching of biomedical databases essential to consider. PMID- 1406422 TI - Mohs surgery explained. PMID- 1406423 TI - Breaking bad news. AB - OBJECTIVE: To investigate the importance of a sympathetic approach to breaking bad news in the doctor-patient relationship. DATA SOURCES: Worldwide surveys of views on truth disclosure by health care professionals, the public, and patients with cancer and other diseases. STUDY SELECTION: Surveys using a Medline Computer Search were identified. DATA EXTRACTION: Twenty-two questionnaire studies. DATA SYNTHESIS: The data obtained demonstrate trends of an increasing wish since 1950 on the part of patients, the public and doctors for more openness. CONCLUSIONS: The skills necessary for breaking bad news well can be acquired through organised undergraduate and postgraduate education which emphasises a good working doctor patient relationship. PMID- 1406424 TI - Factors affecting prescribing in general practice--a role play. PMID- 1406425 TI - Transplantation of the endocrine pancreas in 1992. AB - In 1992, transplantation of the endocrine pancreas is placed at the interface between laboratory research and clinical medicine. Unlike other forms of transplantation, it is not life saving, and yet its potential to treat all patients with insulin dependent diabetes is limited only by the availability of donated organs. Arguably, the long term glucose homoeostasis provided by vascularised pancreas transplantation is the standard by which other forms of endocrine pancreas transplantation (islet cell, fetal islet, and xenogeneic transplantation) must be judged. For the small number of type I diabetic Australians who develop end-stage renal failure and would otherwise require a renal transplant, the combined transplant procedure is a technically viable treatment option and, with some justification, the treatment of choice. PMID- 1406426 TI - Why some people do not drown. Hypothermia versus the diving response. AB - OBJECTIVE: To examine our present state of knowledge regarding the remarkable survival of some victims from prolonged submersion for an hour or more. Debate continues on the relative importance of the two explanatory theories--diving response and hypothermia. DATA SOURCES: A wide range of physiological, pathophysiological and clinical papers relating to the diving response, hypothermia and near-drowning, with emphasis on the period 1981-1991. DATA SYNTHESIS: The normothermic human brain suffers irreversible damage if subjected to acute asphyxia for longer than 10 minutes. Significant resistance of brain tissue to hypoxia occurs only after its temperature has fallen from 37 degrees C to 30 degrees C or less. Body surface cooling depresses core temperature by only one-third of this drop in 10 minutes. Hence an additional factor, other than hypothermia, is required to explain survival from near-drowning. The idea that ingestion and aspiration of large amounts of cold water produce such a temperature drop lacks quantitative evidence. The diving response seen in marine mammals also occurs in humans but to a lesser extent; however, about 15% of volunteers tested exhibit a profound response. This response which starts immediately upon submersion prevents aspiration of water, redistributes oxygen stores to heart and brain, slows cardiac oxygen use and initiates a hypometabolic state. The possible influence of alcohol on these processes is considered. CONCLUSIONS: Survival from prolonged near-drowning appears to depend upon a specific temporal interplay between the diving response and hypothermia, resulting in a protective state of hypometabolism. PMID- 1406427 TI - Ethics committees: is the tail wagging the dog? PMID- 1406428 TI - One weapon for victory. Disease and its prevention as one determinant of the outcome of war. PMID- 1406429 TI - Refusals of medical treatment. PMID- 1406430 TI - Oestrogen and breast cancer. PMID- 1406431 TI - Oestrogen and breast cancer. PMID- 1406432 TI - "Just a mother". PMID- 1406433 TI - Tropical medicine--college or collage? PMID- 1406435 TI - Guidelines for fetal surgery. Research and Ethics Subcommittee. Women's and Children's Hospital. PMID- 1406434 TI - Gastric polyposis: onset during long-term therapy with omeprazole. PMID- 1406436 TI - Meningitis vaccines. PMID- 1406437 TI - [The patient customer]. PMID- 1406438 TI - [Calcitonin gene related peptide. Do neuropeptides effect cardiovascular functions?]. PMID- 1406439 TI - [Seasonal depression. Phototherapy and psychopharmacologic approaches]. PMID- 1406440 TI - [ACE inhibitors in hypertension. A determination of the status]. PMID- 1406441 TI - [Contractile disorders of the heart and calcium]. PMID- 1406442 TI - [Metabolic syndrome and type II diabetes]. PMID- 1406443 TI - [Dr. Wolfgang Wessinger--in memory]. PMID- 1406444 TI - [Caffeine. Clinical pharmacology and use as a drug]. PMID- 1406445 TI - [Fungal infection of the human. 4: Genital mycoses]. PMID- 1406446 TI - [Progress in small steps. Evaluation of the German Cancer Congress in Berlin]. PMID- 1406447 TI - Treatment of Lyme disease. PMID- 1406448 TI - Transdermal fentanyl. PMID- 1406449 TI - Choice of drugs for postmenopausal osteoporosis. PMID- 1406450 TI - Amlodipine--a new calcium-channel blocker. PMID- 1406451 TI - Production, purification and characterization of canine prostromelysin. AB - One of the best studied animal models of osteoarthritis is a dog model in which the anterior cruciate ligament of the hind limb stifle joint is transected (Pond Nuki model). To determine whether stromelysin might play a role in this model, it was necessary to purify the enzyme for production of suitable probes. In the present study, dog synovial fibroblasts were stimulated to express a metalloproteinase that was demonstrated to be canine prostromelysin by Northern blot, protein purification and amino-terminal sequence analyses. Unlike rabbit synoviocytes, passaged dog synoviocytes did not express stromelysin mRNA in response to recombinant human IL-1, but expressed stromelysin mRNA only upon treatment with dog monocyte-conditioned medium (dMCM). The aminophenylmercuric acetate (APMA)-activatable metalloproteinase present in the culture supernatants of stimulated dog synoviocytes was purified using a combination of ion-exchange and dye matrix affinity chromatography. The purified canine metalloproteinase co migrated on reducing SDS-PAGE with recombinant human prostromelysin-1 as a doublet with apparent molecular masses of 54 and 56 kDa. Similar to APMA activated human prostromelysin-1, the APMA-activated canine metalloproteinase was inhibited by 1,10-phenanthroline or recombinant human tissue inhibitor of metalloproteinase (TIMP). The amino-terminal sequences of the canine pro- and APMA-activated enzymes were compared with those of human, rabbit and rat stromelysin. The striking homologies among the sequences demonstrated that the purified canine metalloproteinase was indeed canine prostromelysin. A rabbit anti canine prostromelysin polyclonal antiserum was generated and used to localize the enzyme within cultured dog synoviocytes and articular cartilage stimulated with dMCM. The reagents developed in this study should be useful for examining the expression and distribution of prostromelysin in canine models of osteoarthritis. PMID- 1406452 TI - Long-term neonatal rat aortic smooth muscle cell cultures: a model for the tunica media of a blood vessel. AB - Cultured neonatal rat aortic smooth muscle cells have been used to study the synthesis and accumulation of extracellular matrix components in many laboratories. These cells are capable of accumulating large amounts of insoluble elastin in the extracellular matrix and can be maintained in culture for long periods of time without subcultivation. This study examined the elastin and collagen contents of such cells in culture for 5, 21 and 43 weeks. The percent elastin and collagen observed in the 43-week cultures were strikingly similar to that seen in the intact neonatal rat aorta. It should be noted that the percent collagen varied significantly between 5 weeks and 43 weeks, whereas that for elastin remained relatively constant throughout the same time course. Histological examination demonstrated that the elastin fibers in the extracellular matrix of the cultures were arranged in a pattern similar to the elastic lamellae of the aortic tunica media. Data presented here suggest that these cells in culture mimic the donor tissue from which they were derived with respect to elastin and collagen content as well as elastic fiber arrangement, and possibly represent an organotypic culture of the medial layer of a blood vessel. PMID- 1406453 TI - Dentin phosphophoryn binding to collagen fibrils. AB - The interaction of rat incisor phosphophoryn with native turkey tendon collagen fibers has been examined by electron microscopy. The binding of phosphophoryn to the tendon fibril surfaces is quite selective. The phosphophoryn is seen as positively or negatively stained globular particles predominantly at the "e" band in the collagen gap region in transmission electron micrographs of the phosphophoryn-reacted fibrils. The selectivity of binding to the fibrils was obtained in the presence of calcium ions, which bind avidly to phosphophoryn. The specific association of phosphophoryn at the "e" band suggests a possible regulation of mineral deposition within the gap regions of the collagen fibrils. PMID- 1406454 TI - The stimulation of fibroblasts' collagen synthesis by neoplastic cells is modulated by the extracellular matrix. AB - Human fibroblasts cocultured with neoplastic MCF7 cells produce increased amounts of collagen. A maximal stimulation requires direct cell-cell contacts between tumor cells and fibroblasts. However, this effect could be reproduced, although to a lesser extent, by medium conditioned by MCF7 cells, suggesting that it is mediated by a factor produced by MCF7 cells and secreted, at least partly, under a soluble form (Noel et al., 1992). This Collagen Stimulating Factor ("COSF") present in the culture medium displayed a molecular mass between 3,500 to 10,000 daltons, bound to heparin and appeared to be different from the growth factors described until now. The "COSF" can be released from the surface of MCF7 cells by treatment with heparin. The aim of the present work was to investigate the influence of various extracellular matrix components on the production and the release of "COSF". A 3- to 4-fold enhancement of collagen synthesis was observed in coculture on plastic and collagen type I substrates without significant modification of the non-collagen proteins. The increased collagen synthesis was paralleled by an elevation of specific collagen mRNAs level suggesting a regulation at a pretranslational level. On the opposite, in the presence of soluble or insoluble laminin, this stimulation was abolished. Similarly, coculture on "reconstituted basement membrane matrix", matrigel, did not increase collagen production. The "COSF" was found to bind to matrigel and could be released from the basement membrane matrix by treatment with heparin. PMID- 1406455 TI - Localization of the expression of type I, II, III collagen, and aggrecan core protein genes in developing human articular cartilage. AB - The expression of mRNAs for collagen types I, II, III and for aggrecan core protein was studied in developing human femoral cartilage by in situ hybridization, with special attention given to the cartilage covered by the perichondrium and to the articular surface. In parallel, the synthesis of the related proteins was monitored by immunohistochemistry. The cells metabolically active for type I and type III collagen expression were identified by hybridization using [32P]-labeled cDNA clones coding for human alpha 1(I) and alpha 1(III), respectively. Type II collagen and core protein mRNAs were detected by hybridization with specific [32P]-labeled oligonucleotide probes. In the femoral heads of one 22-week old fetus and of one newborn, our in situ hybridization and immunohistochemical analysis revealed that chondrocytes located immediately subjacent to the perichondrium produced collagen types I, II, III as well as aggrecan; whereas only type II collagen and aggrecan gene expression was detected deeper in the cartilage covered by the perichondrium. This observation supports the hypothesis that the inner cell layers of perichondrium are chondrogenic, with a transient state where cells express all the markers studied here. At the articular surface different patterns of expression were observed at the two developmental stages. After 22 weeks of fetal development only collagen types I and III were expressed by the surface zone cells while in the newborn cartilage, these cells expressed all the molecules studied (collagen types I, II, III and cartilage proteoglycan). At both ages the underlying cartilage cells expressed only the cartilage-specific molecules (type II collagen and aggrecan). Thus a progressive transformation of cartilaginous matrix occurs with time from the deep cartilage up to the surface by addition of new components, i.e. aggrecan and type II collagen. These results supplemented by an immunofluorescence analysis on 20-, 26- and 38-week old fetal femoral heads suggest that expression of collagen and aggrecan in the cartilage covered by the perichondrium and in the cartilage at the articular surface are subject to different regulatory mechanisms during development. Furthermore, the appearance of hybridizable core protein and type II collagen mRNAs at the articular surface, closely followed by the appearance of the proteins for which they code, indicates that core protein and type II collagen expression is regulated primarily at the transcriptional level in this region. Finally, the similar topography observed for the expression of these two proteins suggests that the genes for these two major constituents of cartilage matrix are coordinately regulated during growth of articular cartilage. PMID- 1406456 TI - Isolation and serine protease inhibitory activity of the 44-residue, C-terminal fragment of alpha 1-antitrypsin from human placenta. AB - alpha 1-Antitrypsin (AAT) is a potent fluid-phase inhibitor of serine proteases. It forms a tightly bound, stoichiometric complex with these enzymes and is inactivated by cleavage within its reactive center. Evidence is here presented, that the 44-residue C-terminal fragment of AAT, termed SPAAT (short peptide from AAT), is found in human tissue, where it is apparently bound to the extracellular matrix (ECM). The identity of SPAAT was established by amino acid sequence analysis through its 40 N-terminal residues. Placental SPAAT inhibits chymotrypsin, human neutrophil elastase (HNE) and pancreatic elastase, but has no effect on trypsin. Unlike AAT, both placental and chemically-synthesized SPAAT are reversible, competitive inhibitors of chymotrypsin with Kl's of 0.92 and 7.5 microM, respectively. Both AAT and placental SPAAT also bind to diisopropyl fluorophosphate (DFP)-treated HNE as well as cathepsin G. SPAAT may therefore play an important role in the protection of ECM proteins, such as elastin, proteoglycans (PG) and/or collagen, from inappropriate attack by serine proteases. PMID- 1406457 TI - Isolation and characterization of enzymes hydrolyzing chymotrypsin synthetic substrate (Enzyme I) and trypsin synthetic substrate (Enzyme II) from the envelope of Capnocytophaga gingivalis. AB - Enzymes hydrolyzing chymotrypsin synthetic substrate and trypsin synthetic substrate, referred to as Enzyme I and Enzyme II, respectively, were found in the envelope fraction of Capnocytophaga gingivalis (ATCC 33624). Detergent extraction of both enzymes were purified by gel filtration, ion exchange chromatography, and affinity chromatography. The Enzyme I was a serine-containing metallo enzyme with a molecular mass of 77 kDa. The molecular mass of the Enzyme II was 83 kDa, and it was inhibited by tosyl-L-lysine chloromethyl ketone and leupeptin, and thus may be related to trypsin. PMID- 1406458 TI - Genetic polymorphism of the gene encoding the outer surface protein A (OspA) of Borrelia burgdorferi. AB - The genes coding for the outer surface protein (OspA) of Borrelia burgdorferi, the causative agent of Lyme borreliosis have been cloned and sequenced. Two German strains (skin isolate PKo and cerebrospinal fluid isolate PBi) have been analyzed. Using an OspA-specific monoclonal antibody (L32 2E7) for immunological screening of a genomic pUC18 library of B. burgdorferi strain PKo, and OspA producing clone was detected and subclones containing the open reading frame were constructed. The gene coding for the OspA protein of B. burgdorferi strain PBi was amplified using polymerase chain reaction (PCR) and cloned in pUC8. The open reading frame of both ospA genes consists of 822 nucleotides corresponding to a protein of 273 amino acids. Both proteins have a calculated molecular mass of 29.6 kDa. Molecular analysis revealed significant differences between each other and to already-published sequences of ospA of B. burgdorferi strains B31, ZS7 and N40 (the ospA genes of B31, ZS7 and N40 are nearly identical). The deduced amino acid sequences of the OspA protein of strains PKo and PBi showed a homology of 83% to each other and 77% and 80%, respectively, to OspA protein of strain B31. The three proteins contain a variable middle region, whereas the N and the C terminus are conserved. This unexpected high dissimilarity of the ospA genes may be important in respect to vaccination studies and diagnostic procedures (i.e., development of PCR primers or serodiagnostic antigens). Moreover, the molecular heterogeneity of OspA confirms three out of seven immunologically defined OspA serotypes of a recently proposed OspA serotyping system. PMID- 1406459 TI - Sero-diagnosis of tuberculosis with A60 antigen enzyme-linked immunosorbent assay: failure in HIV-infected individuals in Ghana. AB - In order to assess the diagnostic usefulness of the A60 (ANDA Biological, Strassbourg, France) sero-diagnostic enzyme-linked immunosorbent assay (ELISA) kit for tuberculosis in Africa, sera of 53 pulmonary smear-positive tuberculosis (TB) patients, 30 apparently healthy control subjects and 6 AIDS suspects were sampled in Agogo Hospital in the forest area of Ghana. These sera were analyzed for antibodies to HIV-1 and HIV-2, and IgG-antibodies to the A60 BCG-antigen, while the non-HIV individuals were tested for total IgG levels. One healthy control subject, all of 6 AIDS suspects and 7 of the TB patients has HIV infections. In the non-HIV TB group, the sensitivity and specifity of the A60 ELISA was 78% and 86%, respectively, which was much poorer than expected from published reports about the A60 test. The A60 test failed, completely however, to discriminate between TB and non-TB in the HIV-positive group. In the non-HIV groups, total IgG levels were significantly higher in TB patients than in controls. It seems that the usefulness of the A60 ELISA test to diagnose tuberculosis is very limited in this high-incidence area, and that it seems to be of no value in patients infected with HIV. PMID- 1406462 TI - Redefining security. PMID- 1406460 TI - Antibacterial effect of bovine milk antibody against Escherichia coli in a mouse indigenous infection model. AB - A skim-milk fraction and a whey-protein concentrate (WPC) fraction were prepared from the cows that had been immunized with E. coli isolated from the mouse intestine. The antibacterial effect of these fractions against E. coli was examined. They contained antibody with a high affinity for E. coli strain 48, a representative strain in the mouse intestine, which is composed of a large amount of IgG and smaller amounts of IgA and IgM. Although these fractions showed no bactericidal or bacteriostatic activity against E. coli 48 directly in vitro, they exhibited strong agglutination and opsonization activities against the bacteria in vitro. The bacteria opsonized with the WPC fraction were taken up more effectively by liver macrophages in vivo, compared with unopsonized E. coli, after an intravenous injection into mice. Oral administration of the skim-milk fraction to mice significantly reduced the susceptibility to the lethal toxicity of 5-fluorouracil (5 FU). The increase in the population levels of E. coli in the intestinal tract after administration of 5 FU was inhibited by oral administration of the skim-milk fraction. These results strongly suggest that specific antibody may be effective in the prophylaxis against the indigenous infection with gram-negative bacteria such as E. coli after a period of chemotherapy in cancer patients. PMID- 1406463 TI - Helping victims of violence in Uganda. AB - We report on a project to assist victims of war and violence in Uganda. The original aim of this project, set up by the Medical Foundation for the Care of Victims of Torture, was to establish a centre for the assessment and treatment of torture victims who had suffered during previous regimes in that country. We found, however, that a specialist centre was not the most appropriate response in a country like Uganda. We argue for the need to respect local initiatives and systems of support and against the notion that there is a single model of care which is universally relevant. Following much investigation and involvement with local personnel, we have developed a programme of training and discussion for health workers, and a service to reach the many women who have suffered rape, and whose suffering has continued, largely ignored. PMID- 1406461 TI - Defensins: microbicidal and cytotoxic peptides of mammalian host defense cells. PMID- 1406464 TI - Adaptation after torture: some thoughts on the long-term effects of surviving a repressive regime. AB - The long-term problems of refugee survivors of organized violence are considered. A case example is described in order to illustrate the complexity of factors that contribute to the psychological well-being and social adaptation of such a survivor. The limitations of the classic diagnostic approaches are discussed. It is suggested that measures of social function can be more helpful than a description of symptoms, and should be included in the concept of PTSD, in order to increase the usefulness of this diagnosis in relation to severe and chronic trauma. PMID- 1406465 TI - Health services in Vietnam. AB - This paper reviews the existing health services in Vietnam against the background of 50 years of wars with Japan, France, the United States and neighbouring countries, leaving a devastated economy and thousands of war-wounded, prostitutes, drug addicts and orphans. Defoliation has affected soil fertility and caused miscarriages, stillbirths and deformities. Unexploded bombs still blow off peasants' legs. The prevalence of malaria is increased by the many bomb craters where mosquitoes breed in stagnant water. Superstitions in some ethnic groups contribute to childhood malnutrition. A system is being developed of large provincial hospitals, 100-bed district hospitals and village clinics, incorporating traditional medicine. These are well staffed but poorly equipped. Modern medical and surgical equipment and medicines are urgently needed, but will have to be provided by humanitarian aid until trade links are restored. PMID- 1406466 TI - The nuclear issue in Swedish schools. AB - Sweden is almost unique in that its government through its foreign office gave financial support to a carefully thought out proposal from Svenska Lakare Mot Karnvapen (Swedish Physicians against Nuclear Weapons) for a youth education project on the nuclear issue. The Swedish Board of Education has agreed to provide: 1. In-service training for teachers on current affairs; 2. Up-to-date teaching resources and materials, such as the booklet, Facts and Reflections on Nuclear Weapons; 3. A curriculum stating that education on nuclear and other environment issues should not be a special subject but should be involved in many school activities-for example the learning of foreign languages, biology, physics, science and even physical education. The Board's recommendations have been sent to every Swedish school, together with the booklet, but each school decides for itself whether or not to implement them. However, some teachers do some education on the nuclear issue in most Swedish schools. PMID- 1406467 TI - Effects of prolonged war and repression on a country's health status and medical services: some evidence from Iran 1979-90. AB - The decade following the Islamic revolution in Iran is surveyed from the point of view of the various ways in which the repressive policies of the new regime and, from September 1980, the war with Iraq affected health professionals, medical education and publishing, health services and living conditions. Sources consulted include publications from inside and outside the country, by apologists for and opponents of the regime, and a variety of commentators. Topics studied in more detail are the campaign against drug abuse, the cultural revolution in the universities, the country's leading English-language medical journal, wartime conditions, and the society in the aftermath of the conflict. As well as predating and outlasting the war, the unfavourable climate of repression is seen to have exacerbated its effects in many ways. The population has displayed considerable resilience in the face of overwhelming odds, but the overall picture cannot give much grounds for optimism with regard to either their physical or mental well-being in the future. Particular cause for concern is the profound damage and prolonged neglect sustained by the most basic preconditions for health and medical care. PMID- 1406468 TI - Medical Action for Global Security (MEDACT). PMID- 1406469 TI - Biological effects of low frequency electromagnetic fields. AB - Epidemiological studies since 1979 have raised some medical and much public concern that low frequency electromagnetic fields, such as those of power-lines and in domestic and industrial electrical wiring, may have harmful biological effects. These studies are generally inconsistent, inconclusive, and difficult to replicate. Identifying biological mechanisms by which such harmful effects may occur has proved difficult, although there are several new and promising approaches. In epidemiological and laboratory studies much greater co-ordination and standardization is needed if greater scientific knowledge of these phenomena, as opposed to mere diverse speculation, is to be achieved. PMID- 1406471 TI - [Perforation of gastroduodenal ulcer: a risk analysis]. AB - In 90 patients who, between 1.1.1986 and 31.12.1991, underwent surgery for a perforated gastric/duodenal ulcer, the importance of age, sex, ulcer history, ulcer site, free/covered perforation, extent of peritonitis, duration of history and the pre-operative risk assessment (ASA classification) was analysed with respect to the risk of dying of the perforated ulcer. The univariate analysis showed the following to be prognostically relevant factors: time interval between onset of acute symptoms and surgery (less than or equal to 24 hours: mortality rate 12%, greater than 24 hours: mortality rate 21%; p = 0.006); physical status of the patient as reflected in the ASA category prior to surgery (mortality: ASA II 0%, ASA III 8%, ASA IV 32%; p = 0.009), and the presence of a spontaneous pneumoperitoneum (free perforation 21% mortality, covered perforation 5% mortality; p = 0.049). Investigation of the overall influence of the univariate relevant factors in the logistic model showed a relative risk of 4.9 for duration of history, and of 5.4 for the ASA classification. The mortality risk for a patient who is operated on more than 24 hours after onset of the acute symptoms is 4.9 times that of a patient operated on within 24 hours. In the ASA classification, the mortality risk increases by 5.4 from one category to the next higher one. PMID- 1406470 TI - [Radioimmunoscintigraphy of colorectal tumors with 99m-Tc marked CEA antibodies. Indications and clinical value]. AB - In Germany, radioimmunoscintigraphy (RIS) (scintigraphic, specific imaging of benign and malignant diseases by radioactively labelled monoclonal antibodies) has been employed since 1985 in clinical trials involving patients with colorectal cancer. After proving successful for identifying primary tumors, RIS is now increasingly being used for the early diagnosis of recurrent and metastatic lesions. In this prospective study involving 75 patients with colorectal tumors confirmed by endoscopy and biopsy, it was shown that RIS using the SPECT technique with 99m-Tc-labelled monoclonal CEA antibodies has a sensitivity of 78% in the detection of local recurrent disease in cases in which diagnostic work-up has been inconclusive. PMID- 1406473 TI - [Hickman catheter for long-term parenteral therapy. A prospective interdisciplinary study]. AB - 160 patients with a median age of 38 years (range two months to 84 years) having silicone rubber central venous access catheters for long-term parenteral nutrition or chemotherapy were studied prospectively. Two different types of catheters were used, the Broviac-type "life-cath" and the Groshong -catheter. Intraoperative complications were not noticed. Parenteral therapy was performed in 124 patients (81%) without any complications. After a mean postoperative interval of 36 weeks there were 34 catheters removed because of end of therapy. 78 patients died with the catheter in place. 40 catheters had to be removed before end of therapy due to catheter-related complications. Occlusion of the lumen occurred in nine patients after an interval from three to 20 weeks. Explantation of catheters due to a suspected catheter-related sepsis was performed in 17 patients. Both types of catheter showed a high cumulative patency rate of 90% after a twelve months period. However, there were catheters that had to be removed before planned end of therapy. Thus, the cumulative rate of functioning catheters is lower (44% of all catheters). PMID- 1406472 TI - [Refractory anemia with 5q--anomaly. Clinical picture and follow-up of seven patients]. AB - The clinical picture and the course of the disease of seven patients with the 5q syndrome are described. Examination of peripheral blood revealed refractory anaemia with macrocytosis, anisocytosis, poikilocytosis of erythrocytes, and platelet anisocytosis with some giant platelets. Characteristic bone marrow findings are megaloblastic dyserythropoiesis and micromegakaryocytes with hypolobulated nuclei. Cytogenetically, an interstitial deletion of the long arm of chromosome 5 is always found, associated with a haploid loss of the genes for the growth factors GM-CSF, M-CSF and IL-3. The disease is usually chronic, and only in the case of clonal evolution is there a considerable risk of leukemic transformation occurring. In the chronic phase, infusion of packed red cells as required individually has proved a reliable form of treatment. The results of chemotherapy have disappointed both in the chronic and acute phases of the disease. PMID- 1406474 TI - [Epigastric colic caused by biliary escape of a hydatid entity from an echinococcus cyst]. PMID- 1406475 TI - [Prevention of thromboembolism with a low-dose heparin regimen in acute stroke]. PMID- 1406476 TI - [Diabetic retinopathy: risk factors and therapy concepts]. PMID- 1406477 TI - [Waldenstrom's macroglobulinemia: clinical aspects, diagnosis and therapy]. PMID- 1406478 TI - [Waldenstrom's disease with pulmonary involvement]. PMID- 1406479 TI - [Hemorrhage into the cardia with perforation into the open abdominal cavity after sclerosing of esophageal varices]. PMID- 1406480 TI - [Biopsy of the nasal mucosa in sarcoidosis]. PMID- 1406481 TI - [Clinical diagnosis and neuropathologic examination findings in 20 AIDS patients]. AB - Disorders of the central nervous system (CNS) associated with HIV infections are becoming increasingly important in the area of clinical diagnosis and treatment of patients with AIDS. The aim of this retrospective analysis of 20 patients with AIDS who died in 1989 was to compare clinical diagnosis, neuroradiological findings and treatment with the results of neuropathological studies. The neuropathological examinations revealed primary CNS lymphoma (high-grade non Hodgkin's lymphoma) in seven cases, cerebral toxoplasmosis in four cases, haemorrhagic infarction in three cases, cerebral cryptococcosis in three cases, and one case each of infiltration of the dura by a peripheral Burkitt's lymphoma, cytomegalovirus encephalitis and bacterial meningitis. A remarkably high percentage of CNS lymphomas with no distinct clinical or neuroradiological differentiation criteria were found in this study. On the basis of these data, we conclude that stereotactic biopsy and histological diagnosis should be recommended for patients with focal intracerebral lesions who fail to respond to suitable anti-parasitic treatment. PMID- 1406482 TI - [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia]. AB - Lasting normalisation of uric acid levels after treatment of patients with gout and hyperuricaemia with a combination of 300 mg allopurinol and 60 mg benzbromarone A total of 210 patients (163 men, 47 women) with gout and hyperuricaemia was treated for three months with daily doses of 300 mg allopurinol and 60 mg benzbromarone. During the course of treatment, the uric acid levels decreased to 4.3 +/- 1.3 mg/dl in male, and 4.4 +/- 1.3 mg/dl in female patients. Both of these levels differ significantly from the initial levels (p less than 0.001). Three months after discontinuation of treatment, uric acid levels were 5.7 +/- 1.2 mg/dl in women, and 5.9 +/- 1.4 mg/dl in men, levels that again differed significantly from the initial levels (p less than 0.001); both levels were, however, within the therapeutic range of below 6.4 mg/dl. PMID- 1406483 TI - [39-year-old patient with epigastric pain, meteorism and diarrhea (lambliasis)]. PMID- 1406484 TI - [Combination therapy with anti-arrhythmia agents]. PMID- 1406485 TI - [Imaging procedures in neuromuscular diseases]. PMID- 1406486 TI - [Endosonography of the esophagus]. PMID- 1406487 TI - [Parathyrotoxic crisis with fatal outcome--what can be learned from this?]. PMID- 1406488 TI - Mechanism of action of regulatory proteins encoded by complex retroviruses. AB - Complex retroviruses are distinguished by their ability to control the expression of their gene products through the action of virally encoded regulatory proteins. These viral gene products modulate both the quantity and the quality of viral gene expression through regulation at both the transcriptional and posttranscriptional levels. The most intensely studied retroviral regulatory proteins, termed Tat and Rev, are encoded by the prototypic complex retrovirus human immunodeficiency virus type 1. However, considerable information also exists on regulatory proteins encoded by human T-cell leukemia virus type I, as well as several other human and animal complex retroviruses. In general, these data demonstrate that retrovirally encoded transcriptional trans-activators can exert a similar effect by several very different mechanisms. In contrast, posttranscriptional regulation of retroviral gene expression appears to occur via a single pathway that is probably dependent on the recruitment of a highly conserved cellular cofactor. These two shared regulatory pathways are proposed to be critical to the ability of complex retroviruses to establish chronic infections in the face of an ongoing host immune response. PMID- 1406489 TI - Agents that increase the permeability of the outer membrane. AB - The outer membrane of gram-negative bacteria provides the cell with an effective permeability barrier against external noxious agents, including antibiotics, but is itself a target for antibacterial agents such as polycations and chelators. Both groups of agents weaken the molecular interactions of the lipopolysaccharide constituent of the outer membrane. Various polycations are able, at least under certain conditions, to bind to the anionic sites of lipopolysaccharide. Many of these disorganize and cross the outer membrane and render it permeable to drugs which permeate the intact membrane very poorly. These polycations include polymyxins and their derivatives, protamine, polymers of basic amino acids, compound 48/80, insect cecropins, reptilian magainins, various cationic leukocyte peptides (defensins, bactenecins, bactericidal/permeability-increasing protein, and others), aminoglycosides, and many more. However, the cationic character is not the sole determinant required for the permeabilizing activity, and therefore some of the agents are much more effective permeabilizers than others. They are useful tools in studies in which the poor permeability of the outer membrane poses problems. Some of them undoubtedly have a role as natural antibiotic substances, and they or their derivatives might have some potential as pharmaceutical agents in antibacterial therapy as well. Also, chelators (such as EDTA, nitrilotriacetic acid, and sodium hexametaphosphate), which disintegrate the outer membrane by removing Mg2+ and Ca2+, are effective and valuable permeabilizers. PMID- 1406490 TI - Editing of errors in selection of amino acids for protein synthesis. AB - All living cells must conduct protein synthesis with a high degree of accuracy maintained in the transmission and flow of information from gene to finished protein product. One crucial "quality control" point in maintaining a high level of accuracy is the selectivity by which aminoacyl-tRNA synthetases furnish correctly activated amino acids, attached to tRNA species, as the building blocks for growing protein chains. During selection of amino acids, synthetases very often have to distinguish the cognate substrate from a homolog having just one fewer methyl group in its structure. The binding energy of a methyl group is estimated to contribute only a factor of 100 to the specificity of binding, yet synthetases distinguish such closely related amino acids with a discrimination factor of 10,000 to 100,000. Examples of this include methionine versus homocysteine, isoleucine versus valine, alanine versus glycine, and threonine versus serine. Many investigators have demonstrated in vitro the ability of certain aminoacyl-tRNA synthetases to edit, that is, correct or prevent incorrect attachment of amino acids to tRNA molecules. Several major editing pathways are now established from in vitro data. Further, at least some aminoacyl-tRNA synthetases have recently been shown to carry out the editing function in vivo. Editing has been demonstrated to occur in both Escherichia coli and Saccharomyces cerevisiae. Significant energy is expended by the cell for editing of misactivated amino acids, which can be reflected in the growth rate. Because of this, cellular levels of aminoacyl-tRNA synthetases, as well as amino acid biosynthetic pathways which yield competing substrates for protein synthesis, must be carefully regulated to prevent excessive editing. High-level expression of recombinant proteins imposes a strain on the biosynthetic capacity of the cell which frequently results in misincorporation of abnormal or wrong amino acids owing in part to limited editing by synthetases. Unbalanced amino acid pools associated with some genetic disorders in humans may also lead to errors in tRNA aminoacylation. The availability of X-ray crystallographic structures of some synthetases, combined with site-directed mutagenesis, allows insights into molecular details of the extraordinary selectivity of synthetases, including the editing function. PMID- 1406493 TI - Cost containment and new priorities in the European community. AB - This article reports on the author's survey of the cost-control measures for health care in 12 European countries during the period from 1983 to 1990. Among these countries the greatest convergence was in the use of the budget as a system of control, reinforced by manpower controls. Budgets were constructed to restrict hospital costs and payments to doctors practicing outside of hospitals. Another strategy was cost sharing for purchase of drugs and, in some cases, for dentistry. Most countries took steps to control expensive medical equipment; others, to restrict entry to medical schools. The European experience demonstrates the technical feasibility of the government's controlling health care costs by regulating supply rather than demand. The key to Europe's success in the use of monopsony power, whereby one purchaser dominates the market. The author contends that regulation works in Europe and questions whether the United States can exert similar control over its coalition of insurers and providers in order to rein in its health care expenses. PMID- 1406494 TI - Observations on "Cost containment and new priorities in the European community" by Brian Abel-Smith. AB - A commentary on the article by Brian Abel-Smith briefly explores why the United States lags behind Europe in controlling health care costs. Three important factors are, first, that until recently the real cost of health insurance was not apparent to U.S. workers and political leaders; second, Americans prefer to try competition before resorting to other strategies; and third, responsibility for financing health care is divided among a large number of independent entities, while government regulation is split between the state and federal levels. At the same time, governments and private insurers in the United States have developed new health delivery structures and reimbursement mechanisms that the Europeans may find useful. A convergence of the two systems would be to the benefit of both. PMID- 1406495 TI - Issues regarding health plan payments under Medicare and recommendations for reform. AB - The failures of the market for current Medicare health plans include poor information and price distortions and can be attributed to government policy. Reforms that could improve its structure are annual open enrollment periods, premium rebates from health management organizations (HMOs) to members, and termination of the federal government's subsidy of Medicare supplementary insurance. However, the price for a basic Medicare benefits package would still be distorted because Medicare bases its contribution on the cost of a comparable package in the fee-for-service (FFS) sector rather than on the cost of the most efficient plan available to beneficiaries in each market area. The present Medicare HMO program almost certainly increases total Medicare costs and actually discourages HMO growth by shielding beneficiaries from the true price difference between basic benefits in the HMO and FFS sectors. Lacking payment reforms, the Medicare HMO program should be terminated. PMID- 1406496 TI - Case mix adjusted nursing-home reimbursement: a critical review of the evidence. AB - Nursing-home case mix adjusted payment systems typically base payments on estimates of patients' care needs, but to date the data on their effectiveness are ambiguous. Studies mainly show that access for patients most in need of care appears to improve under these systems. Case mix based payment systems have both positive and negative effects on quality of care and require compensating mechanisms for the potentially harmful incentives they can generate. On the positive side, nursing homes are paid more equitably; the negative aspect is reflected in higher costs, particularly for administration. A Health Care Financing Administration (HCFA) demonstration project may provide insights, but its limited number of predominantly small, rural, participating states, its tandem quality assurance system, and potentially confounding market variables may restrict the value of this project. We do not yet have the data to assess the impact of instituting case mix adjustment systems. PMID- 1406497 TI - Expanding the definition of disability: implications for planning, policy, and research. AB - Disability remains an area that is difficult to define and measure. Rheumatoid arthritis (RA), with its greater impact on women than on men, is one example of this. People with RA are limited in many areas besides paid work, so to measure this disability only in terms of paid work greatly underestimates its impact on people's lives, particularly those of women. This article reviews the major definitions of disability and reports the results of a national study assessing disability in both family and paid work roles. Both areas reveal high rates of disability among RA patients. The study concludes that measuring disability only in terms of paid work seriously underestimates its prevalence among women. These results have important implications for health policy because the greatest needs of the disabled may be, not in income replacement programs, such as Social Security disability programs, but rather in fortifying family and other care services that would enable people with RA to maintain higher levels of function in all domains of life. PMID- 1406492 TI - Microbial reductive dehalogenation. AB - A wide variety of compounds can be biodegraded via reductive removal of halogen substituents. This process can degrade toxic pollutants, some of which are not known to be biodegraded by any other means. Reductive dehalogenation of aromatic compounds has been found primarily in undefined, syntrophic anaerobic communities. We discuss ecological and physiological principles which appear to be important in these communities and evaluate how widely applicable these principles are. Anaerobic communities that catalyze reductive dehalogenation appear to differ in many respects. A large number of pure cultures which catalyze reductive dehalogenation of aliphatic compounds are known, in contrast to only a few organisms which catalyze reductive dehalogenation of aromatic compounds. Desulfomonile tiedjei DCB-1 is an anaerobe which dehalogenates aromatic compounds and is physiologically and morphologically unusual in a number of respects, including the ability to exploit reductive dehalogenation for energy metabolism. When possible, we use D. tiedjei as a model to understand dehalogenating organisms in the above-mentioned undefined systems. Aerobes use reductive dehalogenation for substrates which are resistant to known mechanisms of oxidative attack. Reductive dehalogenation, especially of aliphatic compounds, has recently been found in cell-free systems. These systems give us an insight into how and why microorganisms catalyze this activity. In some cases transition metal complexes serve as catalysts, whereas in other cases, particularly with aromatic substrates, the catalysts appear to be enzymes. PMID- 1406498 TI - Supporting the elderly: workplace programs for employed caregivers. AB - An aging population and extended longevity are increasing the number of older people needing informal and family support. At the same time, women, the traditional caregivers, have entered the work force in record numbers. Consequently, concerns about how to care for dependent family members have become workplace issues. In response to the needs of employees who care for family members, employers have produced an array of policies, benefits, and programs, including flexible work schedules and information and referral services. Although these programs are a valuable complement to community services and government initiatives, relatively few employers have recognized the potential effects of caregiving on absenteeism, productivity, and turnover; even fewer have responded with workplace programs directed to the needs of their caregiving employees. To fill the gap, the government is considering mandating employee benefits, such as leave time for family illness. Community services are increasingly being directed to the needs of older people and their caregivers. PMID- 1406499 TI - World blindness and the medical profession: conflicting medical cultures and the ethical dilemmas of helping. AB - This is an account of a thwarted humanitarian effort and the strategic and ethical issues that is raised. Between 14 and 17 million people in the world are blind with cataract, a condition readily corrected by surgery. In 1989 a proposal was developed to attack this problem by supplying volunteer ophthalmologists to the world's leading private voluntary organizations that carry out programs in less developed countries. The proposal was rejected. This article describes the proposal and the issues on which it foundered: cost effectiveness, appropriate technology, changing ideologies of assistance, and conflict between the cultures of medicine and public health. The account illustrates the far-flung consequences of technological change in medicine, as well as the practical and ethical questions facing organizations that carry out overseas assistance programs. PMID- 1406500 TI - Elevated lead burden in Chinese patients without occupational lead exposure. AB - Studies were conducted in 10 healthy Chinese controls, 10 patients with chronic renal failure without gout, 8 patients with gout complicated with chronic renal failure and in 6 patients with chronic renal failure who subsequently developed gout. All the subjects had no history of occupational or accidental lead exposure. Total body lead burden was assessed by 24-hour urine collection measurements over a 72-hour period after intravenous administration of 1 g of calcium disodium EDTA. The postinfusion urinary lead excretion of the healthy controls (90.2, range 57.2-161.5 micrograms/3 days/1.73 m2) was higher than the values recently reported for healthy German controls. Similar to earlier studies, we failed to find elevated urinary lead excretion in patients with chronic renal failure without gout. Nevertheless, the EDTA mobilization test identified 2 patients with occult plumbism in this group of patients. Our study also clearly demonstrated that 4 of 6 patients with renal failure who developed gout de novo had underlying plumbism. The high prevalence of increased lead body burden in patients with chronic renal failure, in particular those associated with gout, indicates that lead may contribute to a significant portion of chronic renal disease in our patients. In addition, our data suggest that chronic low-level environmental lead exposure may subtly affect renal function. PMID- 1406491 TI - Bacteriophage lysis: mechanism and regulation. AB - Bacteriophage lysis involves at least two fundamentally different strategies. Most phages elaborate at least two proteins, one of which is a murein hydrolase, or lysin, and the other is a membrane protein, which is given the designation holin in this review. The function of the holin is to create a lesion in the cytoplasmic membrane through which the murein hydrolase passes to gain access to the murein layer. This is necessary because phage-encoded lysins never have secretory signal sequences and are thus incapable of unassisted escape from the cytoplasm. The holins, whose prototype is the lambda S protein, share a common organization in terms of the arrangement of charged and hydrophobic residues, and they may all contain at least two transmembrane helical domains. The available evidence suggests that holins oligomerize to form nonspecific holes and that this hole-forming step is the regulated step in phage lysis. The correct scheduling of the lysis event is as much an essential feature of holin function as is the hole formation itself. In the second strategy of lysis, used by the small single stranded DNA phage phi X174 and the single-stranded RNA phage MS2, no murein hydrolase activity is synthesized. Instead, there is a single species of small membrane protein, unlike the holins in primary structure, which somehow causes disruption of the envelope. These lysis proteins function by activation of cellular autolysins. A host locus is required for the lytic function of the phi X174 lysis gene E. PMID- 1406501 TI - Induction of intestinal mucosal atrophy by difluoromethylornithine: a nonuremic model of enhanced aluminum absorption. AB - The intestinal absorption of aluminum (Al) appears to be enhanced in the uremic rat. Since atrophic changes of the intestinal mucosa have been observed in uremia the present study investigated whether intestinal atrophy induced by difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, could affect the absorption of Al. DFMO supplied with the drinking water (5%) to rats with normal renal function for 9 days resulted in a reduced number of microvilli with definite morphological alterations in small intestinal mucosa. Following an oral load of Al urinary excretion rates and 1-hour postload serum concentrations of Al were increased in DFMO-treated rats as compared to controls suggesting enhanced absorption of Al. Pattern and degree of urinary Al excretion as well as ultrastructural alterations of the intestinal mucosa were similar in DFMO-treated rats and uremic rats. The model of DFMO-induced intestinal alterations suggests that structural lesions of the intestine may be involved in the enhanced absorption of Al in uremia. PMID- 1406502 TI - Combined acute hypoxemia and hypercapnic acidosis increases atrial natriuretic polypeptide in conscious dogs. AB - To evaluate the changes in atrial natriuretic polypeptide during acute hypoxemia and acute hypercapnic acidosis, conscious mongrel dogs with controlled sodium intake were evaluated in four protocols: (1) 80 min of acute hypoxemia (PaO2 = 34 +/- 1 mm Hg) followed by 40 min of combined hypoxemia and hypercapnic acidosis (PaO2 = 38 +/- 1 mm Hg, PaCO2 = 60 +/- 3 mm Hg, pH = 7.15 +/- 0.03) (n = 7); (2) 40 min of combined acute hypoxemia and hypercapnic acidosis (PaO2 = 36 +/- 1 mm Hg, PaCO2 = 56 +/- 2 mm Hg, pH = 7.20 +/- 0.03) induced immediately following control measurements (n = 5); (3) 120 min of acute hypercapnic acidosis (PaCO2 = 58 +/- 1 mm Hg, pH = 7.20 +/- 0.01) (n = 5), and (4) 120 min of normoxemia and normocapnia (n = 7). These studies did not observe any association between urinary sodium excretion and circulating atrial natriuretic polypeptide during acute blood gas derangements in conscious dogs. The natriuresis with acute hypoxemia or acute hypercapnic acidosis was unaccompanied by change in plasma atrial natriuretic polypeptide concentrations. Conversely, the rise in circulating atrial natriuretic polypeptide during combined acute hypoxemia and hypercapnic acidosis was not associated with an increase in urinary sodium excretion. These observations do not exclude a role for atrial natriuretic polypeptide in altering sodium excretion during acute blood gas derangements, since the effects of this autacoid on renal sodium excretion may have been offset by other counterregulatory mechanisms of sodium excretion activated during the acute blood gas derangement. PMID- 1406503 TI - Studies of acquired sustained hypernatraemia occurring in a diabetic patient. AB - We describe studies undertaken in a diabetic patient with acquired sustained severe hypernatraemia. Arginine vasopressin levels and thirst scores were grossly subnormal in the presence of marked hypernatraemia but arginine vasopressin increased normally under the influence of negative pressure-induced hypovolaemia. Despite very low levels of arginine vasopressin, polyuria was not a feature suggesting acquired renal hyper-responsiveness. This patient is an additional case of acquired osmoregulatory dysfunction, whose features do not fall neatly into previously described categories. PMID- 1406504 TI - Bartter's syndrome: evidence suggesting a distal tubular defect in a hypocalciuric variant of the syndrome. AB - Renal tubular function was examined in 5 adult patients aged 18-30 years with Bartter's syndrome associated with renal magnesium wasting and hypocalciuria. In the 3 patients studied during hypotonic saline diuresis, distal tubular fractional chloride reabsorption was lower than that reported in normal subjects. In response to a single intravenous dose of furosemide (40 mg), the increment in the excretion of sodium, chloride, and magnesium was equal to or greater than in normal subjects, while in 2 patients, in response to intravenous chlorothiazide (500 mg), the increment in sodium excretion was less than in normal subjects. Magnesium chloride infusion was undertaken in 2 patients in order to compare magnesium and calcium excretions at similar plasma magnesium levels in patients and in normal subjects. The patients exhibited magnesium wasting only at normal or low plasma magnesium levels, while calcium excretion was reduced in the patients at normal and elevated plasma magnesium levels. We conclude that in these patients the enhancement of renal magnesium reabsorption by hypomagnesemia is defective, and the hypomagnesemia is not the cause of the hypocalciuria. The tubule defect responsible for these abnormalities of magnesium and calcium excretion may be located beyond the side of action of furosemide, in the thiazide sensitive segment of the distal convoluted tubule. PMID- 1406505 TI - Inappropriate hypercalcitriolemia in ileum-resected patients with Crohn's disease. AB - Twelve patients who had undergone ileal resection because of Crohn's disease were studied for measurements of serum 25-hydroxyvitamin D3 (25-OHD3), 1,25 dihydroxyvitamin D3 [1,25(OH)2D3], intact parathyroid hormone (PTH), ionized calcium and phosphate in median 6 years after the intestinal resection. 24 normal subjects matched for age, sex and season served as controls. Despite a reduced level of 25-OHD3 (p less than 0.05) and normal levels of ionized calcium, PTH, phosphate and renal function the median level of 1,25(OH)2D3 was significantly raised (p less than 0.001). Further analysis showed that the inappropriately increased level of 1,25(OH)2D3 was significantly positive related to the concentrations of its substrate (25-OHD3) and PTH. The cause for inappropriate hypercalcitriolemia is uncertain. Contribution from extrarenal 1-hydroxylation of 25-OHD3 as in sarcoidosis is suggested. PMID- 1406506 TI - Roles of hormones in plasma potassium alteration in acute respiratory acidosis in dogs. AB - The present study was conducted to examine the roles of hormonal factors in plasma potassium alterations in acute respiratory acidosis. Respiratory acidosis (pH, 7.07-7.10) induced by the inhalation of 10% CO2, 20% O2 and 70% N2 mixed gas caused an increase in the plasma potassium concentration beyond that of the control of 3.44 +/- 0.12 (mean +/- SE) to 4.36 +/- 0.07 mEq/l (p less than 0.01) within 180 min. The plasma norepinephrine concentration was also noted to significantly increase at the same time. Phentolamine (40 micrograms/kg/min i.v.) did not affect the degree of acidosis or acidosis-induced hyperkalemia. No significant changes in the plasma levels of epinephrine, insulin, glucagon, cortisol or aldosterone could be detected. Hormonal factors would thus appear not to be essential to potassium movement from intracellular to extracellular compartments in acute respiratory acidosis. PMID- 1406507 TI - Platelet-activating factor attenuates the arginine vasopressin-induced fall of transepithelial resistance across inner medullary collecting duct monolayers. AB - Platelet-activating factor (PAF) is a vasoactive substance produced in the medulla which may alter Na excretion by the kidney. To examine a possible site and mechanism of action of PAF on the kidney, we evaluated the effects of PAF on transepithelial resistance and intracellular calcium concentration ([Ca2+]i) in cultured rat inner medullary collecting duct cells. Exposure of inner medullary collecting duct (IMCD) cell monolayers to PAF had no significant effect on basal transepithelial resistance. By contrast, incubation of IMCD cells with PAF reversibly blocked the fall in transepithelial resistance induced by arginine vasopressin (AVP): -11.1 +/- 1.4 omega.cm2 with AVP versus -0.02 +/- 1.6 omega.cm2 with PAF and AVP. Exposure of IMCD cells to PAF in Ca-replete medium caused a rise in intracellular calcium from 155 +/- 25 to 491 +/- 68 nM. By contrast, exposure of IMCD cells to PAF in Ca-free medium produced no change in [Ca2+]i. Because the rise in [Ca2+]i induced by PAF was absent in Ca-free medium, transepithelial resistance across IMCD monolayers was examined in calcium-free medium. The effect of PAF to block the fall in transepithelial resistance induced by AVP was maintained in Ca-free medium. These data suggest that PAF modulates the effect of AVP on conductive channels by a mechanism distinct from changes in intracellular calcium. PMID- 1406508 TI - [Current concepts of natural history of childhood asthma]. PMID- 1406510 TI - [A case of growth retardation of rare occurrence]. AB - The Authors describe an uncommon case of growth retardation; the clinical and radiological elements that the Authors to a diagnosis of spondyloepiphyseal dysplasia (SED) are noted; they compare this to other diagnosis of different types of growth retardation, they underline the necessity of taking these rare types into consideration before undergoing diagnostic procedures that would be costly both to the patient and society. PMID- 1406509 TI - [Ewing's sarcoma of the bone. Anatomoclinical study of 424 cases]. AB - The clinic-epidemiologic and prognostic features of 424 cases of Ewing sarcoma observed at "Rizzoli" Institute between 1972-1990 are reported. The incidence of the tumor was higher in the second decade of life with slight predominance in the male sex. The primary lesion was especially localized in the extremity and the ratio lower/upper extremity was 5/1. We did not find, in contrast with other Authors, differences in height or in incidence of congenital malformations when compared to controls. The pain was the first common symptom at debut (90%) followed by swelling (50%) and fever (40%). Diagnosis was made 5.5 months after the first symptom and the delay was due to wrong diagnosis at debut in 3/4 of the patients. Laboratory tests showed anemia in about half of the patients and increased value of ESR (60%) and LDH (40%). Seventy-one of the patients were metastatic at presentation, none of these patients were still living after three years. At a median follow-up of 9 years 43% of the patients with localized disease, treated with adjuvant and neo-adjuvant chemotherapy remained continuously disease free, 53% developed metastatic disease and/or local recurrences and 2% had a second malignancy. In 24% of the patients metastases and/or local recurrences appeared three years after the beginning of treatment. Better prognosis was observed in female patients, without fever at diagnosis, with tumor localized at extremities and with normal value of hemoglobin, ERS and LDH. Regarding the type of treatment, better results were obtained by surgery of the primary tumor and by chemotherapy with four drugs (vincristine, cyclophosphamide, adriamycin dactinomycin) in comparison to radiotherapy of the primary tumor and chemotherapy with three drugs (vincristine, cyclophosphamide, adriamycin). PMID- 1406511 TI - [Fragoso-Cantu syndrome. Description of a neonatal case]. AB - We report on a newborn with psychomotor retardation, muscle hypotonia, typical facies, little subcutaneous fat, arachnodactyloid hands and feet, diffuse cortical and subcortical cerebral atrophy. A comparison is made with the Marfan syndrome and it is concluded that the morphoneurological anomalies are compatible with the diagnosis of Fragoso-Cantu syndrome. PMID- 1406513 TI - [Recombinant CD4-IgG in the treatment of AIDS and correlated syndromes: 1st stage of the study]. PMID- 1406514 TI - Thought for food. PMID- 1406512 TI - [Celiac disease in Piedmont. An epidemiological-clinical study]. AB - The incidence of coeliac disease (CD) was calculated on 304 patients under eighteen who were born in the city of Turin and its province in the years 1975 1989; the prevalence on 494 patients who live in the Piedmont Region. The mean crude yearly incidence was 0.511/1000 (1:1957 live birth). It varied from year to year, reaching minimum values in the years 1984-1987. In a contemporary epidemiological study, the mean crude incidence of CD in Italy was 1.2/1000 (1:833 live birth) twice the rate observed in Turin. The prevalence of paediatric CD in Piedmont was 113 per million inhabitants. Since CD has a normal life expectancy, its prevalence may be expected to increase. In the provinces of Novara, Alessandria and Asti CD prevalence was lower than in the others. Mean age at onset was 6 mos in 1975 and increased to 34 mos in 1989. Mean age at diagnosis was 15 mos in 1981, and 7 yrs in 1989. Symptoms were more numerous and severe in patients under 12 mos of age, and became fewer and often atypical in older children. We can therefore speculate that the trend towards a decreasing incidence of CD in recent years my be due to delayed diagnosis. PMID- 1406515 TI - American Indian health. Providers, communities surmount profound problems. AB - Minnesota's urban and rural Indian communities today face a similar set of complex and daunting health problems. No one overriding issue exists, nor does an overall solution. While staff shortages, a dire lack of Indian health professionals, and inadequate financial resources play a role, poverty, racism, lifestyle, alcoholism, and cultural change and conflict all further complicate health problems for Indian people. PMID- 1406517 TI - Physician liability for failure to remove breast implants. AB - In cases where the failure to remove breast implants later results in injury, physicians may be exposed to liability if it can be shown that the woman would have removed the implants had she received more adequate or complete advice regarding the risks of keeping the implants in place. It is possible that courts may impose liability on physicians for failing to take affirmative steps to remove the implants under limited circumstances. In cases where adequate warnings are given, however, liability will rest only where causation can be shown. Proving causation is always fact-specific and will vary from case to case. In general, it must be established that the physician did not give complete advice and that if better advice had been given, the patient would have had the implants removed, preventing later injury. Physicians have at least three potential defenses to negligence actions regarding the failure to remove breast implants. First, the physician may maintain that he or she warned the patient and that the patient chose to ignore the advice. Second, the physician may rely upon available FDA and manufacturer recommendations that support the physician's advice regarding removal. Finally, the statute of limitations may bar a claim if more than two years have elapsed since the date of treatment. PMID- 1406516 TI - Exertional compartment syndrome in covert mild hemophilia. A case report. AB - A 37-year-old white male experienced unexpected postoperative bleeding after fasciotomy and decompression for left pronator and compartment syndromes of the forearm. He was subsequently diagnosed with a mild form of hemophilia A. One year later, surgery was required for right pronator and compartment syndromes. Pre- and postoperative cryoprecipitate infusions controlled bleeding following the second operation until the patient discontinued his infusions, resulting in a wound hematoma. Covert mild hemophilia is implicated in the pathogenesis of his compartment syndromes. PMID- 1406518 TI - Private pensions. A less taxing alternative. AB - The results of the Joneses' coordinated retirement income and estate planning strategies are as follows: 1. The Joneses maximized their estate assets by converting an inefficient estate asset (the qualified retirement plan) into an efficient estate asset (the income-tax-free death benefit) without jeopardizing their current or future standard of living or the value passed on to their heirs. This allows them to satisfy their conflicting objectives. 2. They added flexibility to their future family gifting plans by providing themselves a secure income for the rest of their lives. 3. They fulfilled their desire to protect their family against government confiscation of retirement plan assets in the event they both die before using all their qualified retirement assets. This private pension plan strategy is obviously not available to everyone, nor is it appropriate for everyone. This solution worked well for this client, but everyone's situation is unique. Before creating such a plan, it is important to review all the factors in an individual's financial picture, including financial and retirement objectives and investment risk tolerance. Although this is an innovative idea that may solve a pension dilemma, it should not be used in place of qualified retirement plans but, rather, used in conjunction with such a plan. The private pension plan does not work with all insurance products or all insurance companies. Choosing the right company and product for each client requires care and expertise. PMID- 1406519 TI - Physician involvement, leadership will help achieve equality. PMID- 1406520 TI - Most physicians have treated an HIV-positive patient. PMID- 1406521 TI - Native American youth. Poor health carries a powerful message. PMID- 1406522 TI - Riding in the HealthRight rodeo. PMID- 1406524 TI - Physicians retire on their own terms. PMID- 1406523 TI - Together, we can make HealthRight work. PMID- 1406525 TI - The Minnesota Fatal Accident Circumstances and Epidemiology Study. Surveillance of occupational fatalities. AB - This report describes the Minnesota Fatal Accident Circumstances and Epidemiology Study (MN FACE), a new federally funded initiative to study fatal injuries in the workplace. Its primary objective is to reduce occupational fatalities. Fatalities due to falls, electrocutions, and asphyxiation caused by entry into confined spaces are currently investigated in Minnesota. MN FACE determines risk factors associated with fatalities then develops interventions for their mitigation or elimination. A comprehensive, statewide surveillance system, including state agencies, associations, organized labor, and industry, has been established to reduce the amount of bias in reporting. PMID- 1406526 TI - The Patient Self-Determination Act. Advance directives available to Minnesota patients. AB - The Patient Self-Determination Act requires most health care institutions to inform patients of their right to refuse medical care and their right to provide advance direction regarding their wishes should they become incompetent. Although the PSDA does not apply to physicians, it will probably increase the demand for communication with patients on such matters. Patients will undoubtedly ask how to formulate advance directives. While physicians should make it clear that they are not providing legal advice to patients on such issues, they may wish to indicate that a guardianship and a living will are options available under Minnesota law. Additionally, as indicated above, a number of arguments exist that durable powers of attorney for health care are valid in Minnesota, as well. Physicians should familiarize themselves with living will forms and may wish to make them available to patients upon request. (Living will forms can be obtained by contacting the Minnesota Medical Association at 612/378-1875.) Patients with questions regarding durable powers of attorney should be advised to seek legal counsel. PMID- 1406527 TI - Physicians should manage the care they provide. PMID- 1406529 TI - Finding success and happiness in retirement. Planning is the key. PMID- 1406528 TI - Retirement doesn't always come easy. PMID- 1406530 TI - Health care reform in Minnesota. Implications for the rural physician. AB - Minnesota's health care reform plan (by any name) is a cost-containment bill with provisions to provide health insurance for some uninsured people, to examine quality of care, to increase support for rural provider education and migration to rural practice, and to develop state and regional health planning procedures. It is an ambitious bill with very tight time frames, vague language, and heavy reliance on regional commissions and volunteer groups that are just now being established. Will it have an impact on rural health care? Undoubtedly, it will. But somewhere between what the bill says and the desired outcome is a void that physicians can help fill with constructive work and criticism. If physicians do not take the lead, someone else will fill that void--nonphysician providers, legislators, bureaucrats, or consumers. Or the structure could implode, taking all of us with it. PMID- 1406531 TI - Women in medicine. The tortuous path to professionalism. PMID- 1406532 TI - Twin cities health care mergers, acquisitions, and affiliations. Implications for independent physician practices. AB - "The health care system in Minnesota, especially in the Twin Cities area, is currently undergoing change that can best be characterized as a consolidation of providers into larger and larger groups (multispecialty clinics, hospital/physician mergers, and expanded HMOs and PPOs). These changes are intended to produce economies of scale, less duplication of services, and better control of costs and quality of health care. Where does this leave the more traditional, smaller multispecialty or single-specialty practices often referred to as 'independents'?... How can independent groups respond to these trends in order to survive in the new health care marketplace?" PMID- 1406533 TI - Cardiopulmonary resuscitation in nursing homes. Continuing concerns. PMID- 1406534 TI - Cardiopulmonary resuscitation in Minnesota nursing homes. PMID- 1406535 TI - Minnesota access to health records. Practical steps to complying with a confusing law. PMID- 1406536 TI - Valuing the primary care patient base. AB - This analysis, albeit limited, can help clinics and integrated health systems with their medical staff planning, and it demonstrates the importance of the primary care patient base as a foundation for health services planning and economic and market strategies. It is important to note, however, that when primary, specialty, subspecialty, surgical, and hospital care are well planned and marketed, it is virtually impossible to identify the relative contribution of each to the overall success of the system. Consequently, primary care physicians should not attribute the value discussed here solely to their efforts. Hospital executives should be mindful of two related issues: First, some administrators remain focused on inpatient services when outpatient services may offer greater economic potential over time. Ambulatory interventional diagnostics and therapeutic procedures (e.g., outpatient surgery) are often undervalued or overlooked in medical staff development plans. The net profits available from additional ambulatory surgical cases can be significant. Second, success in developing a medical staff plan requires more than calculating physician supply and demand ratios. A balance must be struck between meeting the hospital's needs for additional physicians and meeting the needs of the existing medical staff. A number of hospital executives have found that devoting all physician-related resources to recruiting new staff can create resentment among physicians who have remained loyal to their hospitals without financial and other practice incentives and inducements. We encourage multispecialty group practices to become students of primary care development as well and urge them to guard against focusing on the high overhead costs of primary care without recognizing the value of an organized primary care strategy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406538 TI - AIDS update. Kaiser allowed to pursue lawsuit. PMID- 1406537 TI - Women in medicine. A promising future, despite challenging past. PMID- 1406539 TI - Pill combination fights deadly infections. PMID- 1406540 TI - Women physicians break down barriers. PMID- 1406541 TI - [Importance of evoked potentials in the evolutive prognosis of coma during cerebral anoxia in adults]. AB - Ten cases of postanoxic coma have been studied. A clinical neurological examination with study of brainstem reflexes and the EEG recording were made on the first day (J1), the third day (J3) and the tenth day (J10) after the start of the coma. A recording of the visual evoked potentials, the brainstem evoked potentials and the somatosensory potentials combined was made at the same time. A clinical examination is carried out one month after the coma when the patient survives. According to the initial clinical examination, we distinguished 3 groups of subjects. The results show that in group III the visual evoked potentials such as EEG have a slightly significant prognostic value; frequently the near outcome lead to death whereas EEG activity persists and the visual evoked potentials disappear later. On the other hand, the association of brainstem evoked potentials and somatosensory potentials clearly has a higher prognostic value in this group. The disappearance of the shortest brainstem responses and the cortical somatosensory responses is clearly an unfavourable prognosis. This disappearance associated with the end EEG activity is the absolute proof of brain death. On the other hand, the persistence of these responses is of a better prognosis at least on the survival level, but their degradation during evolution is unfavourable. PMID- 1406542 TI - Electrical status epilepticus on eye closure: a case report. AB - The authors present the clinical case of a boy manifesting eyelid myoclonias on eye closure. The corresponding electroencephalographic recording was characterized by unceasing spike activity, constituting a sort of electrical status epilepticus. There was no loss of consciousness or differences between results of neuropsychological tests with eyes open and closed. PMID- 1406543 TI - Partial childhood epilepsy and reaction time: the effect of interictal EEG discharges. AB - A study was conducted on seven children (five females and two males, aged 5.7 13.1 years) affected with partial epilepsy which was well controlled by therapy. A computer was connected on-line to a polygraph and during two EEG recordings, the subject had to react to the appearance of a colored rectangle on the display screen by pushing a key on the keyboard: these events were automatically marked on the trace of a polygraphic channel. By means of Anova analysis it was demonstrated that during the same recording, reactions simultaneous to paroxysmal discharges were not significantly slower than those measured during free intervals. However, in the same patient, reaction times were significantly prolonged during recordings characterized by a higher rate of EEG paroxysmal activity. PMID- 1406544 TI - [Comparative study by computerized EEG of dementia of the ALzheimer type and Parkinson's disease with dementia]. AB - A computerized EEG (cEEG) study was performed in two groups of patients with dementia of the Alzheimer type (DAT) and with Parkinson's disease with dementia (PDD). Compared to control subjects suffering from Parkinson's disease without dementia, both groups demonstrated similar slowing down of background activity. However, there were more low frequency components, defined as between 2.5-7 Hz, and less topographical differentiation in PDD than in DAT. Furthermore, more severe impairment of cognitive functions was observed in DAT, but their psychometric score correlated with slowing down of EEG only in DMP. These observations emphasize the influence of the subcortical/cortical axis both in dementia of Parkinson's disease and in the neurophysiology of the EEG. PMID- 1406545 TI - [Investigation via electroencephalogram with sphenoidal electrodes of a case of reading epilepsy: role of the temporal lobe in the emotional evocation of seizures]. AB - Reading epilepsy in a 20-year-old male. Electroencephalographic study with sphenoidal electrodes localized the onset of critical spikes in the temporal areas (especially the left). The frequency and diffusion of critical spikes were increased when material read had an emotional content. This case report supports the "communication" hypothesis as opposed to hypotheses that emphasize proprioceptive and other "lower order" stimuli in evoking seizures while reading. The authors discuss the role of the temporal lobe in reading: lexical function, treatment of visual information and emotional integration of stimuli. PMID- 1406546 TI - Perineal motor potentials to magnetic stimulation, pudendal evoked potentials and perineal reflex in women. AB - Motor potentials to transcranial and lumbar magnetic stimulation were recorded from the perineum in 14 healthy women. The response to transcranial stimulation presented an onset at 20.2 +/- 1.3 ms and a negative peak at 25.1 +/- 1.9 ms. Lumbar responses presented an onset at 5.1 +/- 0.8 ms, and the motor central conduction time measured 14.4 +/- 1.5 ms. Perineal reflex, cortical and lumbar pudendal evoked potentials were recorded after electrical stimulation of the labia minora. These tests are of possible clinical use in the evaluation of sphincter disturbances as they investigate the afferent and efferent pathways concerning pudendal nerve function. PMID- 1406547 TI - Aplasia cutis congenita: a clinical review and associated defects. PMID- 1406548 TI - Infant definitive care unit: developmental care for the hospitalized NICU graduate. PMID- 1406549 TI - Us against "them": Bush's cynical manipulation of the real issues. PMID- 1406550 TI - The staff nurse and the research team. PMID- 1406551 TI - A review of ventilation-perfusion relationships in the neonatal lung. Part I. PMID- 1406552 TI - Assessment of the quality of the neonatal chest x-ray film. PMID- 1406554 TI - Translating research findings into practice. PMID- 1406553 TI - I'm only human. PMID- 1406555 TI - Education in the NICU. Computer applications for education, Part 1. PMID- 1406556 TI - Albuterol. PMID- 1406557 TI - Neonatal short bowel syndrome. PMID- 1406558 TI - Tick research efforts. PMID- 1406559 TI - Tick research efforts. PMID- 1406560 TI - A prospective study of the transition to phacoemulsification and small incision cataract surgery. AB - Phacoemulsification is an increasingly popular method of performing cataract surgery. The procedure remains controversial. Opponents of phacoemulsification maintain the procedure has an unacceptably high complication rate during transition to the technique. This prospective study found that the many advantages of phacoemulsification were safely introduced into a moderate sized community practice. The surgical complication rate was very low and visual acuity statistics excellent. PMID- 1406561 TI - Esophageal stricture: results of dilation of 300 patients. AB - Three hundred patients underwent 1,177 esophageal dilations over a nine-year period. There were 164 men and 136 women. Mean age was 63 years. Etiology of stricture was peptic (160), Schatzki's ring (124), cancer (8), post-surgical (3), post-radiation (2), caustic ingestion (1), and esophageal web (2). Dilators used were Maloney red-rubber mercury weighted (78.1%), Savary wire-guided (15.2%), Eder-Puestow (6.3%) and Balloon (0.4%). Fluoroscopy was used in 98% of cases. One hundred and two of the 111 patients with peptic strictures observed for longer than six months had successful dilation. Forty-five of these patients (40.5%) required 54 redilations to maintain relief of dysphagia. Nine patients were refractory to dilation, two needing serial dilation and seven surgery. All Schatzki's rings were treated successfully. Ten of 82 patients followed for greater than six months needed redilation (12%). Morbidity was 0.2% with two complications occurring, an esophageal perforation and one case of hematemesis. There was no mortality. PMID- 1406562 TI - Skin expansion as preparation for an opening wedge osteotomy of the mid-foot in arthrogryposis. AB - A case report is presented in which tissue expansion is used to provide the additional skin needed during an opening wedge mid-foot osteotomy to correct a varus foot deformity in a patient with arthrogryposis multiplex congenita. Tissue expansion is a relatively new method of acquiring coverage for wounds which may have advantages over previous techniques. The risks and drawbacks of this technique will be described in detail. PMID- 1406563 TI - Food for thought. PMID- 1406564 TI - Pertussis vaccination: acellular pertussis vaccine for the fourth and fifth doses of the DTP series update to supplementary ACIP statement. Recommendations of the Advisory Committee on Immunization Practices (ACIP). AB - General recommendations on pertussis prevention were issued August 8, 1991, in the ACIP statement on diphtheria, tetanus, and pertussis (1). A supplementary statement on the use of diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) was issued February 7, 1992 (2) after the licensure of ACEL-IMUNE, prepared by Lederle Laboratories. With the recent licensure of a second DTaP product, Tripedia, this statement updates the supplement. Tripedia has a formulation that differs from that of ACEL-IMUNE. Both DTaP vaccines are licensed for use only as the fourth and/or fifth doses of diphtheria, tetanus, and pertussis vaccination; they are not licensed for the initial three-dose series for infants and children, regardless of age. Whole-cell DTP should continue to be used for the initial three-dose series and remains an acceptable alternative for the fourth and fifth doses. For details on the background, indications, use, and precautions and contraindications of DTaP, refer to the earlier supplementary statement (2). PMID- 1406565 TI - Pneumonic plague--Arizona, 1992. AB - On August 26, 1992, a 31-year-old male resident of Tucson, Arizona, died of an illness subsequently diagnosed as primary pneumonic plague. This is the 10th case of plague reported in the United States in 1992, the first pneumonic plague case this year, and the first plague fatality reported since 1987 (CDC, unpublished data). This report summarizes the investigation of this case by county, state, and federal public health officials in Arizona and Colorado. PMID- 1406566 TI - HIV counseling and testing services from public and private providers--United States, 1990. AB - Human immunodeficiency virus (HIV) counseling and testing (CT) services are key elements of the national HIV-prevention strategy (1,2). Although the number and characteristics of persons receiving CT through publicly funded programs are monitored by CDC's CT data system (3), this system does not provide information about persons tested for HIV antibody by physicians in the private sector, hospitals, and other nonpublicly funded sources. This report summarizes data from CDC's 1990 National Health Interview Survey (NHIS) AIDS Supplement (4) regarding CT received from public and private providers. PMID- 1406567 TI - Alcohol-related hospitalizations--Indian Health Service and tribal hospitals, United States, May 1992. AB - Alcohol use is directly responsible for hospitalizations resulting from chronic conditions, such as alcoholic liver disease and alcoholic psychoses; in addition, alcohol use can be a contributing factor in other conditions, such as infectious diseases and injuries, that require hospital admission. Based on discharge data from Indian Health Service (IHS) facilities and CDC's National Hospital Discharge Survey (1), the proportion of alcohol-related hospitalizations (ARHs) among American Indians/Alaskan Natives has been reported as 2.5 times that for the total U.S. population. However, these estimates rely on a limited set of alcohol defined diagnoses that are primarily associated with chronic alcoholism. To characterize more accurately the relation of alcohol use to inpatient admissions to IHS and tribally operated hospitals in the United States, IHS conducted a 1 day survey of ARHs in these facilities on Monday, May 18, 1992. This report summarizes preliminary results from the survey. PMID- 1406568 TI - Behaviors related to unintentional and intentional injuries among high school students--United States, 1991. AB - During 1988, injuries were the leading cause of death among persons aged 15-19 years in the United States (CDC, unpublished data, 1988). Of all deaths in this age group, 42% were motor-vehicle related, 13% were due to homicide, 13% to suicide, and 11% to other types of injuries and adverse effects. This report presents 1991 self-reported data on the prevalence of selected behaviors (i.e., attempted suicide, physical fighting, weapon-carrying, safety-belt use, motorcycle-helmet use, and bicycle-helmet use) associated with these causes of death among 9th-12th-grade students in the United States. PMID- 1406569 TI - National Coalition for Adult Immunization: activities to increase influenza vaccination levels, 1989-1991. AB - Older persons and persons with underlying health problems are at increased risk for complications of influenza infection; however, only 30% of persons aged > or = 65 years are vaccinated against influenza each year (1). This report describes initial efforts by the National Coalition for Adult Immunization's (NCAI) Influenza and Pneumonia Action Group (IPAG) to increase influenza vaccination of adults in the United States during 1990-1993, and highlights National Adult Immunization Week, October 25-31, 1992. PMID- 1406570 TI - Poliomyelitis--Netherlands, 1992. AB - From September 17 through October 9, 1992, five cases of poliomyelitis were reported in the Netherlands among members of religious groups that generally do not accept vaccination. This report summarizes investigations of these five cases by the Netherlands' Office of the Chief Medical Officer of Health, the Laboratory of Virology, National Institute for Public Health and Environmental Protection, and the Municipal Health Services in Rotterdam. The investigation indicated that none of the cases were epidemiologically linked; two of the cases (cases 1 and 2) had some history of receipt of polio vaccine, while three (cases 3-5) had no history of polio vaccination. This report summarizes the investigation of these cases. PMID- 1406571 TI - Lead ingestion associated with ceramic glaze--Alaska, 1992. AB - In August 1992, a physician notified the Alaska Division of Public Health (ADPH) that three patients at a psychiatric hospital had consumed ceramic glaze during ceramic therapy (i.e., recreation therapy involving the production of ceramic ware), and two of these patients had elevated blood lead levels (BLLs). This report summarizes the ADPH's investigation of these ingestions. PMID- 1406572 TI - Public health focus: surveillance, prevention, and control of nosocomial infections. AB - Nosocomial infections are estimated to involve more than 2 million patients annually (1, 2) and in 1992 cost more than $4.5 billion (3). Adverse consequences of nosocomial infections and their associated costs vary by type of infection (Table 1) (3). Hospital-based programs of surveillance, prevention, and control of nosocomial infections were developed during the 1950s and refined in the United States during the 1960s and 1970s. However, questions regarding the efficacy and cost-effectiveness of these programs have persisted. This report examines knowledge about the effectiveness of nosocomial infection surveillance, prevention, and control and their cost-benefits. PMID- 1406573 TI - Plague--United States, 1992. AB - From January 1 through October 15, 1992, 11 human plague cases, including one described recently (1), have been reported in the United States. This report summarizes the epidemiologic information on these cases and provides recommendations for control of plague. PMID- 1406574 TI - Epidemic early syphilis--Montgomery County, Alabama, 1990-1991. AB - In Montgomery County (1990 population: 209,085), Alabama, an epidemic of early syphilis (ES) (i.e., primary, secondary, and early latent) involving 1010 cases occurred from August 1990 through November 1991 (Figure 1). From June 17 through November 7, 1991, the Alabama Department of Public Health (ADPH) and CDC initiated an intervention campaign to reduce the incidence of ES; the intervention increased case-finding primarily through partner notification (PN) and cluster investigations.* This report assesses the intervention campaign by describing 1) the results of PN/cluster investigation interviews during the intervention, 2) the relation between reported crack cocaine use and PN/cluster investigation results, 3) a comparison of interview results for the first 6 weeks of the campaign (i.e., early campaign period) with the 6-week period immediately before the campaign (i.e., precampaign period), and 4) the syphilis morbidity trends for 1990 and 1991. PMID- 1406575 TI - Human psittacosis linked to a bird distributor in Mississippi--Massachusetts and Tennessee, 1992. AB - During April-May 1992, CDC was notified of a possible outbreak of psittacosis involving members of two families in Massachusetts and Tennessee who had recently purchased birds as pets. In the subsequent investigation of this problem, human psittacosis was defined as a fourfold rise in complement-fixing antibody titer to > or = 32 or a single titer of > or = 32 in a patient with fever and/or respiratory symptoms. This report summarizes the investigation of this problem. PMID- 1406576 TI - Nutritional needs surveys among the elderly--Russia and Armenia, 1992. AB - The ongoing social, political, and economic changes in the 15 republics of the former Soviet Union have resulted in hyperinflation of the Soviet Union ruble (SUR), regional conflicts, and other hardships for the populations of these republics (1). In January 1992, a public health assessment in Russia indicated that the elderly--most of whom subsist on fixed incomes and among whom the prevalences of decreased mobility or chronic illnesses may be substantial--are at greatest risk because of declining social support. During March-May 1992, CARE, in collaboration with CDC, conducted three surveys in Russia and Armenia to assist in targeting the delivery of food and medical humanitarian aid to the most needy among the elderly. This report summarizes findings from these surveys. PMID- 1406577 TI - Chaparral-induced toxic hepatitis--California and Texas, 1992. AB - Cases of acute toxic hepatitis in two patients--one in California and one in Texas--have been attributed to ingestion of an herbal nutritional supplement product derived from the leaves of the creosote bush known commonly as chaparral. This report summarizes the investigations of these cases. PMID- 1406578 TI - Anonymous survey for simian immunodeficiency virus (SIV) seropositivity in SIV laboratory researchers--United States, 1992. AB - CDC recently reported on two laboratory workers who had seroconverted against simian immunodeficiency virus (SIV) following work-related exposure to the virus. In follow-up, the National Institutes of Health (NIH) and CDC have collaborated on an anonymous SIV seroprevalence study using stored serum samples from some laboratory workers and animal caretakers involved in SIV research at some of the NIH-sponsored facilities in the United States. This report summarizes the study. PMID- 1406579 TI - Surveillance for occupationally acquired HIV infection--United States, 1981-1992. AB - Public health surveillance for and risk-assessment studies of human immunodeficiency virus (HIV) infection provide a basis for formulating measures to minimize the risk for occupational transmission of HIV to health-care workers (1-6). Data on occupational transmission of HIV have been provided by two CDC supported national surveillance systems: one initiated in 1981 for acquired immunodeficiency syndrome (AIDS) cases and one initiated in 1991 for HIV infections acquired through occupational exposures (Table 1). This report summarizes data on occupationally acquired HIV infection from these surveillance systems through September 1992. PMID- 1406580 TI - Community awareness and use of HIV/AIDS-prevention services among minority populations--Connecticut, 1991. AB - Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) prevention efforts supported by the federal government include programs offered through community-based organizations (CBOs) and state and local health departments (1). To assess the extent of community awareness and use of these HIV/AIDS-prevention services among Hispanics and non-Hispanic blacks in three cities in Connecticut, the Connecticut State Department of Health Services (CSDHS) included questions on HIV/AIDS-prevention programs in its population based chronic disease and health risk survey. This report summarizes survey results regarding awareness and use of these community-based programs during 1991. PMID- 1406581 TI - ATPase activity of SopA, a protein essential for active partitioning of F plasmid. AB - The sopA, B, C genes of the F plasmid play an essential role in plasmid partitioning during cell division in Escherichia coli. In this paper, the products of the sopA and sopB genes were isolated and their biochemical activities studied. [alpha-32P]ATP was cross-linked to the SopA protein by UV irradiation; this cross-linking was observed only in the presence of magnesium ion, and was competitively inhibited in the presence of non-radioactive ATP, ADP and dATP, but not other NTPs or dNTPs. In contrast, no ATP binding activity was detected for the SopB protein. The SopA protein showed a modest magnesium ion dependent ATPase activity and this activity was stimulated in the presence of DNA. The ATPase activity in the presence of DNA was further stimulated by addition of the SopB protein. However, the SopB protein alone failed to stimulate the ATPase activity. PMID- 1406582 TI - A deletion derivative of the kalilo senescence plasmid forms hairpin and duplex DNA structures in the mitochondria of Neurospora. AB - A novel deletion derivative, delta kal, of the kalilo senescence plasmid from Neurospora intermedia, was recovered from a culture treated with chloramphenicol. The deletion derivative exists in mitochondria as two different, equally abundant forms: a 2.8 kb duplex DNA molecule (delta kal-2.8) and a 1.4 kb hairpin form (delta kal-1.4). The delta kal-2.8 plasmid contains the 1366 bp terminal inverted repeats and a partially duplicated 102 bp segment of the unique sequence of the 8.6 kb kalilo plasmid. In contrast, the delta kal-1.4 hairpin plasmid appears to result from the folding of single strands that are generated during the replication of delta kal-2.8. Both forms of delta kal have covalently linked terminal proteins. Sequence analysis suggests that delta kal was generated either by slippage of the tip of a growing strand during the replication of kalilo, or by illegitimate recombination between two copies of the plasmid at non-homologous palindromic sequences that might form cruciform structures. In either case, the deletion process was mediated at least in part by an inverted repeat of 5 bp in the unique region of kalilo. Since the terminal segments of kalilo DNA that are implicated in plasmid integration might also form cruciform structures, it is possible, but improbable, that the process that generated the first delta kal molecule is related to that which mediates integration of the plasmid into mitochondrial DNA. PMID- 1406583 TI - Translational readthrough at nonsense mutations in the HSF1 gene of Saccharomyces cerevisiae. AB - The HSF1 gene of Saccharomyces cerevisiae directs the synthesis of the heat shock transcription factor, HSF. The gene is essential; disruption mutations are lethal. Using a plasmid shuffle screen, we isolated mutations in the HSF1 gene after in vitro mutagenesis of plasmid DNA with hydroxylamine. From a collection of both conditional (temperature-sensitive) and unconditional lethal mutations, we recovered mutations that map exclusively to the 5' half of the gene. All are nonsense mutations, including conditional mutations that map 5' to the portion of the HSF1 gene that encodes the DNA-binding domain of the transcription factor. For one such mutation, we demonstrated that the nonsense mutation is subject to translational readthrough, even though there are no known nonsense suppressors in the genetic background of our strain. Our results suggest that the HSF protein is highly tolerant of amino acid changes, a conclusion that is consistent with the very low degree of evolutionary conservation among HSF proteins. Our results also suggest that translational readthrough occurs with moderate efficiency in yeast, particularly when the terminator codon is followed immediately by an A or C residue. This result illustrates that the inference of gene function from mutant phenotype depends critically upon the analysis of a true null allele, and not merely an amber or ochre allele. PMID- 1406584 TI - Brassica anther-specific genes: characterization and in situ localization of expression. AB - A cDNA library of Brassica napus (cv. Westar) was constructed using poly(A)+ RNA isolated from developing anthers of flower buds 2-3 mm in length. Differential hybridization, using cDNA probes complementary to poly(A)+ RNA from developing anthers or seedlings, was used for initial screening. In addition to Southern and Northern blot analyses of selected clones, RNA-PCR assays and in situ hybridization were used to study the temporal and spatial gene regulation in anthers at the transcriptional level. Five independent cDNA clones, showing no cross-hybridization to one another, were characterized, and their expression patterns could be grouped into three distinct categories. Two cDNA clones, BA112 and BA158, are tapetum-specific: the corresponding mRNAs accumulate in young anthers and decline as the tapetum cells degenerate later in anther development. The transcripts represented by BA54 and BA73 accumulate late in anther development and reach a maximum level in mature anthers prior to anthesis; BA54 has been confirmed to be pollen-specific. The third category, represented by BA42, is found to encode a protein sharing 64-67% amino acid similarity with chalcone synthase (CHS) from various plant species; the transcript is localized in the peripheral cells of the vascular bundle, tapetum, and developing microspores. PMID- 1406586 TI - Protein export elements from Lactococcus lactis. AB - Broad-host-range plasmids carrying alpha-amylase or beta-lactamase reporter genes lacking a signal sequence were used to select export elements from Lactococcus lactis chromosomal DNA that could function as signal sequences. Fragments containing such elements were identified by their ability to direct the export of the reporter proteins in Escherichia coli. Several of the selected export elements were also active in Bacillus subtilis and L. lactis, although the efficiencies depended strongly on the host organism and reporter gene used. The export elements AL9 and BL1 were highly efficient in L. lactis in the expression and secretion of at least two heterologous proteins (Bacillus licheniformis alpha amylase and E. coli TEM-beta-lactamase). AL9 even permitted growth of this organism on starch as the sole carbon source. Nucleotide sequence analysis of five selected fragments indicated that these encode oligopeptides with the major characteristics of typical signal peptides. The putative expression signals had a limited similarity to previously described expression signals for E. coli, B. subtilis and L. lactis. Differences in both expression and export efficiency are likely to underlie the host-specific effects. PMID- 1406587 TI - Ammonia regulation of the Rhizobium meliloti nitrogenase structural and regulatory genes under free-living conditions: involvement of the fixL gene product? AB - The expression under microaerobic conditions of the Rhizobium meliloti nifA and consequently the nifHDK genes was found to be negatively regulated by ammonia and nitrate. Assimilation of the ammonia to glutamate and glutamine is not required for this regulation to occur. This indicates that ammonia itself, and not a product of its metabolism, may be regulating nif expression. Unlike the situation in Klebsiella pneumoniae, NtrC is apparently not involved in mediating the ammonia effect on nifA expression in R. meliloti. Neither does the fixK gene product, which is known to regulate nifA in R. meliloti, appear to be involved in mediating the ammonia effect. The regulation of nifA by ammonia is shown to be mediated through the FixL protein. A truncated fixJ gene, the product of which has been shown to induce nifA expression irrespective of the oxygen status of the cell, also circumvented the repressive effect of ammonia on nifA expression. This suggests that the ammonia effect is mediated through the FixLJ regulatory cascade. Interestingly no effect of ammonia on fixK expression was observed. PMID- 1406585 TI - Multiple plant RNA binding proteins identified by PCR: expression of cDNAs encoding RNA binding proteins targeted to chloroplasts in Nicotiana plumbaginifolia. AB - Pre-mRNA processing in eukaryotic cells requires the participation of multiple protein factors and ribonucleoprotein particles. One class of proteins involved in this process are RNA-binding proteins, which contain a domain of ca. 90 amino acids with a characteristic ribonucleoprotein consensus sequence (RNP-CS). A PCR approach that is suitable for the characterization of RNP-CS-type proteins is described. Fifteen different RNA-binding domains were amplified from Nicotiana tabacum (tobacco) using oligonucleotide primers specific for the sequences (K/R)G(F/Y)(G/A)FVX(F/Y) and (L/I/V)(F/Y)(V/I)(G/K)(N/G)L, which are conserved in known RNP-CS proteins. Using the tobacco domains as probes, cDNAs encoding two RNA-binding proteins, each containing two RNP-CS-type domains, were characterized in N. plumbaginifolia. The proteins, designated CP-RBP30 and CP-RBP31, are targeted to chloroplasts as demonstrated by expression of epitope-tagged cDNAs in transfected protoplasts, followed by indirect immunofluorescence. High levels of mRNA for each protein were found in leaves but not in roots, and expression of the CP-RBP31 mRNA was strongly regulated by light. The N. plumbaginifolia proteins described in this work are distinct from chloroplast RNA-binding proteins characterized recently in tobacco and spinach. PMID- 1406588 TI - Insertional disruption of the nusB (ssyB) gene leads to cold-sensitive growth of Escherichia coli and suppression of the secY24 mutation. AB - The Escherichia coli gene ssyB was cloned and sequenced. The ssyB63 (Cs) mutation is an insertion mutation in nusB, while the nusB5 (Cs) mutation suppresses secY24, indicating that inactivation of nusB causes cold-sensitive cell growth as well as phenotypic suppression of secY24. The correct map position of nusB is 9.5 min rather than 11 min as previously assigned. It is located at the distal end of an operon that contains a gene showing significant homology with a Bacillus subtilis gene involved in riboflavin biosynthesis. PMID- 1406589 TI - A defined amino acid exchange close to the putative nucleotide binding site is responsible for an oxygen-tolerant variant of the Rhizobium meliloti NifA protein. AB - In Rhizobium meliloti the NifA protein plays a central role in the expression of genes involved in nitrogen fixation. The R. meliloti NifA protein has been found to be oxygen sensitive and therefore acts as a transcriptional activator only under microaerobic conditions. In order to generate oxygen-tolerant variants of the NifA protein a plasmid carrying the R. meliloti nifA gene was mutagenized in vitro with hydroxylamine. About 70 mutated nifA genes were isolated which mediated up to 12-fold increased NifA activity at high oxygen concentrations. A cloning procedure involving the combination of DNA fragments from mutated and wild-type nifA genes allowed mapping of the mutation sites within the central part of the nifA gene. For 17 mutated nifA genes the exact mutation sites were determined by DNA sequence analysis. It was found that all 17 mutated nifA genes carried identical guanosine--adenosine mutations resulting in a methionine- isoleucine exchange (M217I) near the putative nucleotide binding site within the central domain. Secondary structure predictions indicated that the conformation of the putative nucleotide binding site may be altered in the oxygen-tolerant NifA proteins. A model is proposed which assumes that at high oxygen concentrations the loss of activity of the R. meliloti NifA protein is due to a conformational change in the nucleotide binding site that may abolish binding or hydrolysis of the nucleotide. Such a conformational change may be blocked in the oxygen-tolerant NifA protein, thus allowing interaction with the nucleotide at high oxygen concentrations. PMID- 1406590 TI - Characterization and nucleotide sequence of the oriT-traM-finP region of the IncFVII plasmid pSU233. AB - By hybridizing the IncFVII haemolytic plasmid pSU233 with a probe containing the origin of transfer of the IncFII plasmid R1, we isolated a 1.9 kb BglII fragment containing at least the origin of transfer (oriT), and the genes traM and finP. Functional complementation analysis of deletion derivatives was used to map the origin of transfer. We also determined the nucleotide sequence of traM and finP. Comparison with similar regions of several plasmids, also belonging to the Rep FIIA family, revelaed that pSU233 resembles the F plasmid by very close. The homology is not evenly distributed along this region, but clustered into homologous regions (TraZb-oriT, TraMb-oriT and traM separated by non-homologous regions (TraYb-oriT, finP). This organization resembles that reported for the replication region and also suggests evolution by exchange of modules. In addition, the nucleotide sequence of finP is different from those previously described for other IncF plasmids and constitutes a new allele, which we have denominated allele VI. PMID- 1406592 TI - Sugarbeet minicircular mitochondrial DNAs: high-resolution transcript mapping, transcript abundance and copy number determination. AB - Three minicircular mitochondrial DNAs have been studied to address several aspects of transcription in sugarbeet mitochondria. High-resolution transcript mapping experiments have shown that sequences at the 5' termini of minicircle transcripts are highly homologous and resemble sequences at the 5' termini of sugarbeet mainband mitochondrial genes (atpA, atp6). In addition, they show homology to transcript termini of mitochondrial genes from other dicotyledonous plants, suggesting they may function as promoter sequences. Conserved sequences, which most probably act as RNA processing signals, were also identified at the 3' termini of minicircle transcripts. An oligonucleotide probe to a 14 base conserved sequence was used to determine the relative copy numbers of the three minicircle components in male-fertile mitochondria. Copy numbers were roughly equivalent, suggesting minicircles are replicated and/or transmitted with nearly equal efficiency, at least in sugarbeet taproots. Mc.a and Mc.c transcript levels are equivalent, consistent with their template copy number, however; Mc.d transcript levels were significantly lower than expected, implicating additional factors such as promoter strength and/or transcript stability in determining transcript levels in sugarbeet mitochondria, as recently demonstrated in maize. PMID- 1406591 TI - Mutations in the cdc10 start gene of Schizosaccharomyces pombe implicate the region of homology between cdc10 and SWI6 as important for p85cdc10 function. AB - The cdc10 gene of the fission yeast Schizosaccharomyces pombe is required for traverse of start and commitment to the mitotic cell division cycle rather than other fates. The product of the gene, p85cdc10, is a component of a factor that is thought to be involved in regulating the transcription of genes that are required for DNA synthesis. In order to define regions of the p85cdc10 protein that are important for its function a fine structure genetic map of the cdc10 gene was derived and the sequences of 13 cdc10ts mutants determined. The 13 mutants tested define eight alleles. Eleven of the mutants are located in the region that contains the two copies of the cdc10/SWI6 repeat motif, implicating it as important for p85cdc10 function. PMID- 1406593 TI - Molecular cloning, characterization and purification of ornithine carbamoyltransferase from Mycobacterium bovis BCG. AB - A genomic library of Mycobacterium bovis BCG has been constructed by cloning DNA partially digested with Sau3A into the Escherichia coli expression vector pAS1. The gene coding for ornithine carbamoyl-transferase (EC.2.1.3.3; OTCase), hereafter referred to as argF, was isolated from the library by complementation of a double argF-argI mutant of E. coli and its sequence was determined. The translation initiation codon used, GTG, was identified by comparing the amino acid sequence deduced from the gene with the N-terminal sequence of the corresponding purified protein. On this basis, the M. bovis BCG OTCase monomer consists of 307 amino acid residues and displays about 44% identity with other OTCases, the most closely related homologue being the anabolic enzyme of Pseudomonas aeruginosa. The native enzyme has an estimated molecular mass of 110 kDa, suggesting a trimeric structure as is the case for most of the anabolic OTCases known from various organisms. PMID- 1406595 TI - Development of a transformation system for the thermophilic fungus Talaromyces sp. CL240 based on the use of phleomycin resistance as a dominant selectable marker. AB - A transformation system for the thermophilic cellulolytic fungus Talaromyces sp. CL240 has been developed, using the phleomycin resistance gene from Streptoalloteichus hindustanus (Sh ble) as a dominant selectable marker. The plasmids (pAN8-1 and pUT720) carrying the Sh ble gene under the control of the Aspergillus nidulans glyceraldehyde-3-phosphate dehydrogenase (gpd) promoter, allowed selection of phleomycin-resistant transformants. A new promoter sequence cloned from chromosomal DNA of Trichoderma reesei (pUT737) was also able to drive efficient expression of the Sh ble gene in Talaromyces sp. CL240, resulting in the selection of transformants that were highly resistant to phleomycin. PMID- 1406594 TI - Molecular cloning of the imidazoleglycerolphosphate dehydratase gene of Trichoderma harzianum by genetic complementation in Saccharomyces cerevisiae using a direct expression vector. AB - The Trichoderma harzianum imidazoleglycerolphosphate dehydratase gene (igh) has been isolated by complementation of a Saccharomyces cerevisiae his3 mutant using a direct expression vector. This Escherichia coli-yeast shuttle vector was developed to allow efficient cloning and expression of cDNA libraries. The cDNA is 627 nucleotides long and codes for a protein of 209 amino acids with an apparent molecular mass of 22,466 daltons. The predicted protein sequence showed 63.6%, 58.7%, and 38.4% identity respectively to the corresponding enzymes from S. cerevisiae, Pichia pastoris and E. coli. Northern analysis showed that the expression of the igh gene in T. harzianum is not inhibited by external histidine and the level of igh mRNA was about threefold higher in cells starved of histidine. PMID- 1406596 TI - Homologous recombination between plasmid and chromosomal DNA in Bacillus subtilis requires approximately 70 bp of homology. AB - To determine the minimal DNA sequence homology required for recombination in Bacillus subtilis, we developed a system capable of distinguishing between homologous and illegitimate recombination events during plasmid integration into the chromosome. In this system the recombination frequencies were measured between ts pE194 derivatives carrying segments of the chromosomal beta-gluconase gene (bglS) of various lengths and the bacterial chromosome, using selection for erythromycin resistance at the non-permissive temperature. Homologous recombination events, resulting in disruption of the bglS gene, were easily detected by a colorimetric assay for beta-gluconase activity. A linear dependence of recombination frequency on homology length was observed over an interval of 77 bp. It was found that approximately 70 bp of homology is required for detectable homologous recombination. Homologous recombination was not detected when only 25 bp of homology between plasmid and chromosome were provided. The data indicate that homology requirements for recombination in B. subtilis differ from those in Escherichia coli. PMID- 1406597 TI - Cloning, pharmacological characterization, and chromosome assignment of the human dopamine transporter. AB - We have screened a human substantia nigra cDNA library with probes derived from the rat dopamine transporter. A 3.5-kilobase cDNA clone was isolated and its corresponding gene was located on the distal end of chromosome 5 (5p15.3). This human clone codes for a 620-amino acid protein with a calculated molecular weight of 68,517. Hydropathicity analysis suggests the presence of 12 putative transmembrane domains, a characteristic feature of sodium-dependent neurotransmitter carriers. The rat and the human dopamine transporters are 92% homologous. When permanently expressed in mouse fibroblast Ltk- cells, the human clone is able to induce a saturable, time- and sodium-dependent, dopamine uptake. This transport is blocked by psychostimulant drugs (cocaine, l- and d amphetamine, and phenyclidine), neurotoxins (6-hydroxydopamine and N-methyl-4 phenylpyridine (MPP))+), neurotransmitters (epinephrine, norepinephrine, gamma aminobutyric acid, and serotonin), antidepressants (amitriptyline, bupropion, desipramine, mazindol, nomifensine, and nortriptyline), and various uptake inhibitors (mazindol, GBR 12783, GBR 12909, and amfonelic acid). The rank orders of the Ki values of these substances at the human and the rat dopamine transporters are highly correlated (r = 0.998). The cloning of DNA human dopamine transporter gene has allowed establishment of a cell line stably expressing the human dopamine transporter and, for the first time, an extensive characterization of its pharmacology. Furthermore, these newly developed tools will help in the study of the regulation of dopamine transport in humans and in the clarification of the potential role of the dopamine transporter in a variety of disease states. PMID- 1406598 TI - Agonist binding to rat brain somatostatin receptors alters the interaction of the receptors with guanine nucleotide-binding regulatory proteins. AB - To investigate the interaction of guanine nucleotide-binding regulatory proteins (G proteins) with the agonist-bound brain somatostatin (SRIF) receptor, rat brain SRIF receptor/G protein complexes were solubilized and immunoprecipitated with peptide-directed antisera selective for the different subtypes of G protein alpha subunits (G alpha). In the absence of agonist, solubilized SRIF receptor/G proteins complexes could be immunoprecipitated by antiserum 8730, which is directed against the carboxyl-terminal region of Gi alpha and recognizes all Gi alpha subtypes, and by antiserum 3646, which selectively interacts with internal regions of Gi alpha 1. In contrast, antiserum 1521, which is directed against an internal region of Gi alpha 2, and antiserum 9072, which is directed against the carboxyl-terminal region of Go alpha, did not immunoprecipitate the SRIF receptor. After the binding of agonist to solubilized SRIF receptors, antisera 9072 and 1521, as well as antisera 8730 and 3646, were able to immunoprecipitate the agonist-bound SRIF receptor/G protein complexes, indicating that agonist interaction with SRIF receptors maintained receptor association with Gi alpha 1 and promoted receptor association with Go alpha and, to a lesser extent, Gi alpha 2. Antiserum 1518, which is directed against Gi alpha 3, uncoupled SRIF receptors from Gi alpha and did not immunoprecipitate the agonist-bound or agonist-free brain SRIF receptor. These findings indicate that differences exist in the interaction of the agonist-free and agonist-bound SRIF receptors with G proteins. The binding of agonists to SRIF receptors promotes the association of the receptor with Go alpha and, to a lesser extent, Gi alpha 2, indicating that these G proteins, along with Gi alpha 1 and Gi alpha 3, may be involved in coupling SRIF receptors to cellular effector systems. PMID- 1406599 TI - Ionic zinc may function as an endogenous ligand for the haloperidol-sensitive sigma 2 receptor in rat brain. AB - In the search for an endogenous sigma transmitter, whose existence was previously suggested by release studies, we tested the effects of releasable substances known to be present in the hippocampus, and we determined that ionic zinc may function as an endogenous ligand for the haloperidol-sensitive sigma 2 site. Zn2+ displaced 1,3-di(2-[5-3H]tolyl)guanidine ([3H]DTG) from two binding sites in rat brain membranes, with an IC50 for the high affinity site of 110 +/- 3 microM and for the low affinity site of 20 +/- 4 mM. The sigma 1-selective ligand (+) [3H]pentazocine was only weakly displaced from rat brain membranes by Zn2+ (IC50 = 1.4 +/- 0.05 mM). These results indicate that the Zn(2+)-sensitive sigma binding site corresponds to the sigma 2 site. The interaction between Zn2+ and the sigma 2 site may have physiological significance, because ionic zinc is present in synaptic vesicles in the brain and may function to regulate binding at the sigma 2 site. To test this hypothesis, we measured the effects of metallothionein peptide 1, a specific zinc chelator, on the actions of the putative endogenous sigma ligand(s) released in the hippocampus by focal electrical stimulation. Release of the endogenous sigma ligand(s) was measured by competition with specific radioligand binding in live hippocampal slices. High frequency, focal, electrical stimulation of the zinc-containing mossy fibers in the hilar region of the hippocampus caused a decrease in the specific binding of [3H]DTG, (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, or (+) [3H]pentazocine to sigma sites. The decrease in [3H]DTG binding was largely blocked by metallothionein peptide 1, whereas the decrease in (+)-[3H]pentazocine binding was unaffected. These results suggest that Zn2+ may act as an endogenous ligand at sigma 2 sites in the rat hippocampus. PMID- 1406600 TI - Differential effects of ethanol on electrical properties of various potassium channels expressed in oocytes. AB - The effects of ethanol on a number of electrophysiological parameters were examined in 10 different voltage-gated potassium channels expressed in Xenopus oocytes. None of the channels examined was highly sensitive to ethanol, but there was significant variability among the channels tested at concentrations of ethanol of 200 mM and greater. The response to ethanol was not determined exclusively by membership in a genetic subfamily. In addition, the relative sensitivity among different channels could vary independently for different electrical parameters. For example, current amplitude in DRK1 was insensitive to ethanol, even at concentrations as high as 600 mM, whereas this was one of the more sensitive channels with respect to the kinetics of current inactivation. The opposite situation was true for ShA1. Therefore, ethanol at high concentrations may selectively perturb discrete regions of channel proteins. This is supported by the finding that removal of 318 amino acids from the cytoplasmic carboxyl terminus of DRK1 results in a channel whose current amplitude shows greater sensitivity to ethanol than does DRK1. Thus, the effects of ethanol on the channel may not be limited to interactions at the lipid-protein interface. PMID- 1406601 TI - Stereochemical aspects of benzodiazepine binding to human serum albumin. I. Enantioselective high performance liquid affinity chromatographic examination of chiral and achiral binding interactions between 1,4-benzodiazepines and human serum albumin. AB - The displacement of a series of 1,4-benzodiazepine (BDZ) drugs from a chiral stationary phase, based upon human serum albumin, for high performance liquid chromatography was investigated. The different displacement patterns obtained using various mobile phase additives could not be interpreted in terms of binding of the solutes to a single site. The observations were better described by considering the attachment of the BDZs to several loci on the protein. Two main mechanisms of binding were discerned, a nonstereoselective mode, which affected all solutes and seemed to occur at a large number of locations on the protein, and a highly stereoselective mode, which involved only one enantiomer of chiral BDZs and presumably one conformation of certain achiral solutes. The stereoselective binding mode encompassed at least four different sites, each of which displayed slightly different structural requirements. It is suggested that the nomenclature currently used to describe drug binding to human serum albumin may be misleading. Rather than the use of site I or site II, it may be preferable to adopt the terms type I and type II binding, according to the displacement patterns of the compound concerned. This approach would retain the conceptual simplicity of the current notation, while avoiding misleading implications of the exact molecular locus of binding. PMID- 1406602 TI - Stereochemical aspects of benzodiazepine binding to human serum albumin. II. Quantitative relationships between structure and enantioselective retention in high performance liquid affinity chromatography. AB - Previously determined retention data for a series of benzodiazepine (BDZ) derivatives, comprising nine achiral compounds, four single enantiomers, and 18 individual isomers of nine racemates, on a chiral stationary phase based on immobilized human serum albumin (HSA) were analyzed to define quantitative relationships between structure and enantiospecific retention. Structural parametrization of the agents was done by means of hydrophobic fragmental constants and electronic and steric parameters obtained by computational chemistry methods. A structural descriptor was identified, a submolecular measure of polarity about the stereogenic center, that accounted for the stronger electrostatic interactions of the second-eluting enantiomer with the HSA chiral stationary phase. Quantitative structure-enantiospecific retention relationships were derived for both enantiomeric series and for achiral compounds, and structural requirements for binding to HSA were determined. Two types of binding sites were postulated. For BDZs in the P-conformation, binding to HSA involved a hydrophobic region with steric restrictions. For BDZs in the M-conformation, a hydrophobic region was also involved, as well as a cationic region that interacted electrostatically with carbon C(3) of the diazepine system and substituents at that carbon. These differences lead to different binding patterns for BDZ enantiomers and provide a rationalization for the diversified behavior of individual BDZs that was observed in previous displacement studies. PMID- 1406603 TI - Nucleotide specificity of human deoxycytidine kinase. AB - The ability of deoxycytidine kinase (dCK) to phosphorylate 2'-deoxycytidine (dCyd) and its analogs in the presence of eight nucleoside triphosphates (NTPs), simulating the cellular milieu, was investigated. Using highly purified dCK from MOLT-4 T lymphoblasts, Km and Vmax values were determined for the phosphorylation of dCyd in the presence of cellular concentrations of the eight endogenous NTPs. The results demonstrated that the efficiency of dCyd phosphorylation was greatest in the presence of all eight nucleotides, relative to ATP alone, according to relative Vmax/Km values. UTP was a better phosphate donor than ATP but was less efficient than the NTP mixture. The greater efficacy of the NTP mixture, compared with ATP alone, was due in large part to the presence of UTP, although the results suggested that the presence of other nucleotide(s) also enhanced dCyd phosphorylation. Previous results demonstrated that dCTP was a potent competitive or noncompetitive (with respect to dCyd) inhibitor of dCK, with a Ki value of approximately 1 microM. In contrast, the results presented here demonstrated that, in the presence of either the NTP mixture or UTP, inhibition of dCK was uncompetitive with respect to dCyd, with a Ki value of approximately 60 microM. Furthermore, the results demonstrated that the clinically relevant nucleoside analogs 1-beta-D-arabinofuranosylcytosine, 2',2'-difluoro-2'-deoxycytidine (dFdC), and 9-beta-D-arabinofuranosyl-2-fluoroadenine also preferred UTP or the NTP mixture, compared with ATP alone, as a phosphate donor. Of the three nucleoside analogs tested, dFdC was the most efficient dCK substrate. These data indicate that the preferred phosphate donor for dCK is UTP or a combination of UTP and another nucleotide. Furthermore, the dCTP concentration in intact cells, which is typically 10-20 microM, is not sufficient to cause substantial inhibition of dCK, due to the presence of UTP. Strategies to increase cellular dCK activity should focus on optimizing UTP concentrations. PMID- 1406604 TI - Relationship between DT-diaphorase-mediated metabolism of a series of aziridinylbenzoquinones and DNA damage and cytotoxicity. AB - A series of 2,5-bis-substituted 3,6-diaziridinyl-1,4-benzoquinones have been tested for their ability to be reduced by the two-electron NAD(P)H:(quinone acceptor) oxidoreductase [DT-diaphorase (DTD); EC 1.6.99.2]. Symmetrically alkyl substituted carbamoyl ester analogs of 2,5-ethyl(carboethoxyamino)3,6 diaziridinyl-1,4- benzoquinone [AZQ], 3,6-diaziridinyl-1,4-benzoquinone (DZQ), and its 2,5-dimethyl derivative (MeDZQ) were tested. The rate of reduction by DTD was DZQ greater than MeDZQ greater than n-butyl- (D5) greater than sec-butyl- (D7) greater than n-propyl- (D3) greater than methyl- (D1) greater than ethyl- (AZQ) greater than i-butyl- (D6) greater than i-propyl- (D4) substituted derivatives. The hydroxyethylamino analog (BZQ) was not a substrate for DTD. The order of toxicity to HT-29 human colon carcinoma cells (at 1-log cell kill) was MeDZQ greater than DZQ greater than BZQ greater than D1 greater than D5 greater than AZQ greater than D7 greater than D3 greater than D6 greater than D4. Dicumarol, a known inhibitor of DTD, was capable of inhibiting the cytotoxicity of DZQ, MeDZQ, AZQ, D3, D4, D5, D6, and D7, with little inhibition of D1 cytotoxicity. Alkaline elution assays suggested that DZQ induced DNA strand breaks, whereas MeDZQ induced DNA interstrand crosslinks in HT-29 cells. The formation of both classes of lesions was inhibited by dicumarol. DZQ and MeDZQ were 5-6-fold less cytotoxic to the DTD-deficient BE cell line, whereas BZQ was more cytotoxic to this cell line than the HT-29 cell line. BZQ was capable of inducing dicumarol-insensitive DNA interstrand crosslinks in both cell lines. In summary, these data show a trend between the rate of reduction by DTD of an analog and its ability to induce cytotoxicity in HT-29 cells, and they support a role for DTD in the bioreductive activation of AZQ and its analogs. PMID- 1406606 TI - [Pleitropic resistance in yeast and its connection with multiple resistance in higher eukaryotes]. PMID- 1406605 TI - Suggested mechanism for the modulation of the activity of NAD(P)H:quinone acceptor oxidoreductase (DT-diaphorase) by menadione: interpretation of the effect of menadione on 5'-[p-(Fluorosulfonyl)benzoyl]adenosine labeling of rat liver NAD(P)H:quinone acceptor oxidoreductase. AB - 5'-[p-(Fluorosulfonyl)benzoyl]adenosine (5'FSBA) was previously shown to be an active site-directed affinity label of rat liver NAD(P)H:quinone acceptor oxidoreductase [Mol. Pharmacol. 35:818-822 (1989)]. Our recent study revealed that menadione, the substrate of this quinone reductase, had a magnifying effect on inactivation of the enzyme by 5'-FSBA. The dissociation constant for the initial reversible enzyme-inhibitor complex was significantly lower and the rate of inactivation was increased when menadione was present during the incubation. However, [14C]5'FSBA labeling was reduced in the presence of menadione. These results are presented and a possible mechanism for the enzyme is discussed. PMID- 1406607 TI - [Four-stranded complexes of oligonucleotides--quadruplexes]. AB - The review presents analysis of the experimental, model and calculation studies concerned with the formation of the four-stranded helices of the natural and synthetic oligonucleotides. Guanine-rich oligonucleotides form stable four stranded helices. Structures of such complexes were investigated by means of X rays and spectrographic methods. These works have been reviewed in the first part. There are three possible variants of noncanonical structures formed by oligoguanylic acids. Two of them--four-stranded helices differed by the mutual direction of the sugar-phosphate chains. The third one is the two-stranded hairpin. Regulation of the number of cellular processes by means of the structural conversions between these three forms of guanine-rich motifs are investigated in articles reviewed in the second part. These works are concerned with the structural organization and functions of telomers, and on the other hand with the possible role of quadruplexes in self-recognition processes of the four homologous chromatids during meiosis and the following recombination. The third part of the review considers quadruplexes with an arbitrary sequence. In general there are model works inspired by investigations of recombination and replication processes. Experimental data concerned with the formation of quadruplex structures from two decamer Watson-Crick base paired duplexes oligo(dA).oligo(dT) are also presented. PMID- 1406608 TI - [Association of proteinases with histones from rat thymus nuclei]. AB - Histone H2A, H2B, and H1--specific proteinases tightly associated with histones were shown to be present in rat thymus nuclei. The activity of proteinases tightly associated with histones increases after exposure of animals to gamma rays. The denatured DNA activated the histone H1-specific proteinase. These proteinase dissociated from histones in the presence of dithiothreitol. The histones and proteinases were divided into fractions by chromatography on DEAE cellulose in the presence of 5 mM dithiothreitol. PMID- 1406609 TI - [Determination of potato spindle tumor viroid and chrysanthenum stund viroid using biotinylated olideoxyribonucleotides]. AB - A 26 base long oligodeoxyribonucleotide complementary to a common RNA sequence of potato spindle tuber viroid (PSTV) and chrysantemum stunt viroid (CSV) was synthesized. The 3'-end biotinylated one was used for the detection of PSTV and CSV RNA immobilized on nitrocellulose filters by nucleic acid hybridization. Visualization of hybridization results was performed by two ways, either by streptavidin-alkaline phosphatase conjugate or streptavidine and biotinylated alkaline phosphatase. It was possible to detect 0.65 ng of purified CSV and PSTV RNA. The suggested system of viroid diseases detection can be used by agricultural and horticultural enterprises. PMID- 1406610 TI - [Mycoplasma restriction-modification system MunI and its possible role in pathogenesis processes]. AB - The restriction-modification system, named RMMunI, has been purified and characterised from Friend murine erythroleukemia cells. The site-specific endonuclease recognizes and cleaves the 5'C1AATTG nucleotide sequence. RMunI is an isoschizomer of RMfeI from Mycoplasma fermentans. Site-specific methylase modifies the second adenine residue in the same sequence (5'Cam6ATTG). It was established that the discovered enzymatic system is from mycoplasma which contaminates cell lines. Mycoplasma's DNA hybridizes with species-specific DNA probed for Mycoplasma fermentans and Mycoplasma arginini. The possible role of mycoplasmic restriction-modification enzymes in the process of acquired immune deficiency syndrome are discussed. PMID- 1406612 TI - [New packing of B-DNA in crystals]. AB - Two crystal forms of the self-complementary tetramer GpGpCpC have been obtained by phase diagram technique: P6(2)22/P6(4)22. a = b = 67.7 A, c = 105.6 A and P3(2)12/P3(1)12, a = b = 116.9 A. c = 116.4 A. Both crystals form diffract at least up to 3.2 A. Diffraction patterns of both crystal forms have strongest base stacking reflections corresponding to the Bragg spacing 3.38 A which is typical for B-DNA. Moreover the self-rotation function of the first crystal form shows regular located two-fold pseudo-axes periodicity of which also indicates that this is B-conformation. The same conclusion can be reached on the basis of the crystal packing of the duplexes in the unit cell. It should be emphasized that this is a new example of B-DNA crystal packing. PMID- 1406611 TI - [Study of the spatial structure of globular proteins by tritium planigraphy. Short peptides as a model of a fully extended polypeptide chain]. AB - The interaction of tritium atoms with amino acid residue from short peptides was studied. The short peptides were considered as a model of extended polypeptides chain. Every residue in this chain has 100% steric accessibility. It was shown that: 1. The linear correlation exists between the residue accessible surface area (that is composed of hydrocarbon fragments) and the amount of tritium interacting with this residue; 2. The presence of the tertiary carbon atom in the residue side chain influences on the reactivity of this residue; 3. The N- or C terminal residue presence does not influences on the possibility of interaction of this residue with tritium atoms. The obtained reactivity scale of amino acid residues is compared with other theoretical and experimental data. PMID- 1406613 TI - [Nitrogen mustard fixes the Z-conformation in poly[d(G-C)]poly[d(G-C)] and DNA]. AB - The reactions of poly(dG-dC).poly(dG-dC) and (dG-dC)10 insert in the plasmid pGC20 with N-methyl-bis(2-chloroethyl)-amine (nitrogen mustard, HN-2) have been studied. It is shown that nitrogen mustard does not induce the B----Z transition in poly(dG-dC).poly(dG-dC), but produces fixation of the polynucleotide Z conformation once this exists. In the case of pGC20 plasmid DNA, nitrogen mustard also fixes Z-form of the (dG-dC)-insert. The rate constant of the reaction of nitrogen mustard with guanine in the polynucleotide (k = 9,0.10(-3) min-1) is about one-third of that for the fixation of Z-form of the (dG-dC)-insert in the plasmid (k1 = 2,8.10(-2) min-1) which is attributed to a greater rate of formation of diguanyl derivative in the opposite DNA chains. It is suggested that nitrogen mustard is capable of fixing the Z-form DNA not only in vitro, but also in vivo. PMID- 1406614 TI - [Pea (Pisum sativum) genes, participating in symbiosis with nitrogen-fixing bacteria. III. Study of the structure of the ENOD12 early nodulin gene for various types of peas using the polymerase chain reaction (PCR)]. AB - We have determined the length of early noduline gene ENOD12 in various varieties and lines of pea (Pisum sativum) using the polymerase chain reaction (PCR). It was demonstrated that promoter regions of ENOD12A and ENOD12B genes in line 2150 (Afghanistan) are longer than these in variety "Feltham first". The disparity is 14 bp. When studying these genes in 7 different lines and varieties of pea it was found that ENOD12A gene is more variable in size than the ENOD12B gene. We showed the possibility to analyze the heritage of ENOD12 gene's alleles by using the PCR method. PMID- 1406616 TI - [Interaction of the toxic plant protein--ricin, with model membranes. A fluorescence method of study]. AB - The fluorescence method has been used to investigate ricin and its isolated subunits interaction with some model membranes. Three liposome types were used as a model of biological membrane: 1) liposomes constructed from lecithin and cholesterol (9:1, M:M) 2) from ganglioside receptors GM1 and 3) from the mixture of GM1, lecithin and cholesterol (1:9:1). Interaction of the protein with liposome evokes changes in the parameters of both intrinsic protein fluorescence and fluorescence of the covalently bound dansyl. Binding constants were calculated from a decrease of the intrinsic fluorescence intensity as well as from the changes in the dansyl rotation anisotropy. Measurements were carried out at neutral and acidic pH. There was good correlation of the results obtained by different methods. It was shown that association constants were different for intact ricin and its subunits. The constants also depend on liposome composition and pH of the solution. The present study has demonstrated that interaction of ricin with liposome is accounted for not only by receptor centers but also by other hydrophobic regions of ricin that are inaccessible in the native toxin and may represent the region of the subunits interaction. PMID- 1406615 TI - [Cloning, primary structure determination and expression of preproinsulin cDNA from human insulinoma in Escherichia coli]. AB - A human insulinoma cDNA library was constructed in expression plasmid vector pUEX1. Clone pUEX1Ins12 was selected from human insulinoma cDNA library by means of hybridization with the insulin probe and a nucleotide sequence of the insertion was determined. It codes for full size amino acid sequence preproinsulin and furthermore, contains the entire 3'-end of noncoding mRNA region and 44 nucleotides from the 5'-untranslated region. The bacterial strain pUEX3Ins8 producing preproinsulin as beta-galactosidase fusion protein was constructed. PMID- 1406617 TI - [New 5'-phosphonates, modified through the nucleoside sugar residue, as inhibitors of HIV replication]. AB - A number of nucleoside 5'-phosphonates and nucleoside 5'-methylphosphonates were synthesised, to study their ability to inhibit reproduction of HIV-1. Three compounds, 5'-hydrogen phosphonates of 3'-azido-2',3'-dideoxythymidine (AZT-HP, IVc), 3'-fluoro-2',3'-dideoxythymidine (FLT-HP, IVa) and 2',3'-dideoxyadenosine (ddA-HP, I), exhibit potent anti-HIV-1 activity with selectivity indices similar to or better of those of their parent nucleosides. PMID- 1406618 TI - [Suppression of transcription of influenza virus RNA by oligonucleotide derivatives]. AB - The inhibitory effects of oligonucleotide derivatives on the transcription of virus RNA in an in vitro system and synthesis of virus proteins was studied. Oligonucleotide derivatives d(T)3, d(T)4, d(T)8, d(T)10, d(CCAAACA), d(TCACCCTC), d(TTCCCATT), d(AATACTCT) and d(TGACCCTCTTCCCATT), that bear residues of ethidium, deuteroporphyrin and its complexes with Fe3+, hemin, cholesterol, deuterocholesterol, estrone and naphthoquinone at the 5'-end phosphate and/or at the 3'-end phosphate were studied. Unmodified oligonucleotides and their derivatives had a negligible effect on the synthesis of cellular proteins, but did inhibit the synthesis of influenza virus proteins. The majority of structural modifications increased the inhibitory effect of oligonucleotides. It was shown that the oligonucleotide derivatives carrying residues of porphyrin, quinone, ethidium, cholesterol, deuterotestosterone and estrone at concentrations near 10 mM inhibit virus development to 50-80%. A clear inhibitory effect (20-25%) of deuteroporphyrin, cholesterol and ethidium derivatives was revealed even at concentration 0.1 mM. The obtained results testified that the inhibition of influenza virus development is dependent on the interaction of oligonucleotide derivatives with the transcription complex proteins. PMID- 1406619 TI - Unusual aspects of in vitro RNA processing in the 3' regions of the GAL1, GAL7, and GAL10 genes in Saccharomyces cerevisiae. AB - A striking feature of the 3'-end regions in polymerase II transcripts of Saccharomyces cerevisiae adjacent to their processing and polyadenylation sites is the lack of well-defined signal elements. Nonetheless, essential signals have seemed to be confined to compact regions in vivo, and we find that a short RNA with only 70 bases of GAL7 sequence upstream and 8 to 10 bases downstream of the poly(A) addition site is processed in vitro, as is an analogous CYC1 pre-RNA. Specific polyadenylation of a precleaved species further delimits the poly(A) signal and rules out obligatory coupling between cleavage and poly(A) addition. Although little proximal and even less distal sequence is required for accurate cleavage with CYC1 and GAL7, we have been unable to identify common features to which processing could be ascribed. We therefore turned to the coregulated set of genes in the galactose cluster (GAL1, GAL7, and GAL10) to assay their corresponding pre-mRNAs in vitro, in hopes of finding a common theme. By contrast to GAL7, short pre-mRNAs corresponding to GAL1 and GAL10 fail to be cleaved detectably, and only much longer transcripts are susceptible to processing. This indicates that signals, even if preserved, are more widely dispersed than the poly(A) addition site, and these results are unchanged whether extracts are from cells grown on glucose or galactose. As a further surprise, RNAs corresponding to the antisense orientation of the 3'-end regions of all three GAL genes are also effective substrates for the processing machinery in vitro. Computer analysis reveals the presence of polydisperse dyad symmetries that might account for these observations. PMID- 1406620 TI - Regulated expression of a mammalian nonsense suppressor tRNA gene in vivo and in vitro using the lac operator/repressor system. AB - We have exploited the Escherichia coli lac operator/repressor system as a means to regulate the expression of a mammalian tRNA gene in vivo and in vitro. An oligonucleotide containing a lac operator (lacO) site was cloned immediately upstream of a human serine amber suppressor (Su+) tRNA gene. Insertion of a single lac repressor binding site at position -1 or -32 relative to the coding region had no effect on the amount of functional tRNA made in vivo, as measured by suppression of a nonsense mutation in the E. coli chloramphenicol acetyltransferase gene following cotransfection of mammalian cells. Inclusion of a plasmid expressing the lac repressor in the transfections resulted in 75 to 98% inhibition of suppression activity of lac operator-linked tRNA genes but had no effect on expression of the wild-type gene. Inhibition could be quantitatively relieved with the allosteric inducer isopropylthio-beta-D-galactoside (IPTG). Similarly, transcription in vitro of lac operator-linked tRNA genes in HeLa cell extracts was repressed in the presence of lac repressor, and this inhibition was reversible with IPTG. These results demonstrate that the bacterial lac operator/repressor system can be used to reversibly control the expression of mammalian genes that are transcribed by RNA polymerase III. PMID- 1406621 TI - Different chromatin structures along the spacers flanking active and inactive Xenopus rRNA genes. AB - The accessibility of DNA in chromatin to psoralen was assayed to compare the chromatin structure of the rRNA coding and spacer regions of the two related frog species Xenopus laevis and Xenopus borealis. Isolated nuclei from tissue culture cells were photoreacted with psoralen, and the extent of cross-linking in the different rDNA regions was analyzed by using a gel retardation assay. In both species, restriction fragments from the coding regions showed two distinct extents of cross-linking, indicating the presence of two types of chromatin, one that contains nucleosomes and represents the inactive gene copies, and the other one which is more cross-linked and corresponds to the transcribed genes. A similar cross-linking pattern was obtained with restriction fragments from the enhancer region. Analysis of fragments including these sequences and the upstream portions of the genes suggests that active genes are preceded by nonnucleosomal enhancer regions. The spacer regions flanking the 3' end of the genes gave different results in the two frog species. In X. borealis, all these sequences are packaged in nucleosomes, whereas in X. laevis a distinct fraction, presumably those flanking the active genes, show a heterogeneous chromatin structure. This disturbed nucleosomal organization correlates with the presence of a weaker terminator at the 3' end of the X. laevis genes compared with those of X. borealis, which allows polymerases to transcribe into the downstream spacer. PMID- 1406622 TI - Characterization of Spi-B, a transcription factor related to the putative oncoprotein Spi-1/PU.1. AB - We have cloned a human cDNA from a new gene, spi-B, on the basis of its homology with the DNA-binding domain of the Spi-1/PU.1 putative oncogene product. spi-B codes for a protein of 262 amino acids presenting 43% overall identity with Spi 1. Its highly basic carboxy-terminal region exhibits 34% sequence identity with the DNA-binding domain of the Ets-1 protein. We showed that the Spi-B protein is able to bind the purine-rich sequence (PU box) recognized by Spi-1/PU.1 and to activate transcription of a reporter plasmid containing PU boxes. Chromosome in situ hybridization allowed us to map spi-B to the 19q13.3-19q13.4 region of the human genome. spi-B, like spi-1, was found to be expressed in various murine and human hematopoietic cell lines except T lymphoid cell lines. PMID- 1406623 TI - The ARS consensus sequence is required for chromosomal origin function in Saccharomyces cerevisiae. AB - Replication origins have been mapped to positions that coincide, within experimental error (several hundred base pairs), with ARS elements. To determine whether the DNA sequences required for ARS function on plasmids are required for chromosomal origin function, the chromosomal copy of ARS306 was deleted and the chromosomal copy of ARS307 was replaced with mutant derivatives of ARS307 containing single point mutations in domain A within the ARS core consensus sequence. The chromosomal origin function of these derivatives was assayed by two dimensional agarose gel electrophoresis. Deletion of ARS306 deleted the associated replication origin. The effects on chromosomal origin function of mutations in domain A paralleled their effects on ARS function, as measured by plasmid stability. These results demonstrate that chromosomal origin function is a property of the ARS element itself. PMID- 1406624 TI - RPC53 encodes a subunit of Saccharomyces cerevisiae RNA polymerase C (III) whose inactivation leads to a predominantly G1 arrest. AB - RPC53 is shown to be an essential gene encoding the C53 subunit specifically associated with yeast RNA polymerase C (III). Temperature-sensitive rpc53 mutants were generated and showed a rapid inhibition of tRNA synthesis after transfer to the restrictive temperature. Unexpectedly, the rpc53 mutants preferentially arrested their cell division in the G1 phase as large, round, unbudded cells. The RPC53 DNA sequence is predicted to code for a hydrophilic M(r)-46,916 protein enriched in charged amino acid residues. The carboxy-terminal 136 amino acids of C53 are significantly similar (25% identical amino acid residues) to the same region of the human BN51 protein. The BN51 cDNA was originally isolated by its ability to complement a temperature-sensitive hamster cell mutant that undergoes a G1 cell division arrest, as is true for the rpc53 mutants. PMID- 1406625 TI - Identification of a 60-kilodalton Rb-binding protein, RBP60, that allows the Rb E2F complex to bind DNA. AB - Several reports have indicated that the product of the retinoblastoma gene (Rb) complexes with the transcription factor E2F. We present evidence that the DNA binding of the Rb-E2F complex involves another cellular factor. Addition of Rb to purified preparations of E2F does not generate an Rb-E2F complex that can bind DNA, and in fact, we see an inhibition of the DNA-binding ability of E2F. On the other hand, addition of Rb to cruder preparations of E2F results in the formation of an Rb-E2F complex (E2Fr) that can bind DNA and produces a distinct complex in gel retardation assays. We have identified and purified a 60-kDa protein that allows the Rb-E2F complex to bind DNA, and we show that this 60-kDa protein exerts its effect by directly interacting with Rb. PMID- 1406627 TI - The plant amino acid mimosine may inhibit initiation at origins of replication in Chinese hamster cells. AB - An understanding of replication initiation in mammalian cells has been hampered by the lack of mutations and/or inhibitors that arrest cells just prior to entry into the S period. The plant amino acid mimosine has recently been suggested to inhibit cells at a regulatory step in late G1. We have examined the effects of mimosine on cell cycle traverse in the mimosine [corrected]-resistant CHO cell line CHOC 400. When administered to cultures for 14 h after reversal of a G0 block, the drug appears to arrest the population at the G1/S boundary, and upon its removal cells enter the S phase in a synchronous wave. However, when methotrexate is administered to an actively dividing asynchronous culture, cells are arrested not only at the G1/S interface but also in early and middle S phase. Most interestingly, two-dimensional gel analysis of replication intermediates in the initiation locus of the amplified dihydrofolate reductase domain suggests that mimosine may actually inhibit initiation. Thus, this drug represents a new class of inhibitors that may open a window on regulatory events occurring at individual origins of replication. PMID- 1406626 TI - Differential effects of carboxy-terminal sequence deletions on platelet-derived growth factor receptor signaling activities and interactions with cellular substrates. AB - Chimeric receptors composed of the human epidermal growth factor receptor (EGF-R) extracellular domain fused to wild-type and truncated platelet-derived growth factor receptor (PDGF-R) intracellular sequences were stably expressed in NIH 3T3 cells devoid of endogenous EGF-Rs. This experimental system allowed us to investigate the biological activity of PDGF-R cytoplasmic-domain mutants in PDGF R-responsive NIH 3T3 cells by activating PDGF-specific signaling pathways with EGF. Deletion of 74 carboxy-terminal amino acids severely impaired the ability of the PDGF-R cytoplasmic domain to associate with cellular substrates in vitro. This deletion also inhibited receptor and substrate phosphorylation, reduced the receptor's mitogenic activity, and completely abolished its oncogenic signaling potential. Surprisingly, removal of only six additional amino acids, including Tyr-989, restored substantial receptor and substrate phosphorylation capacity as well as transforming potential and yielded a receptor with wild-type levels of ligand-induced mitogenic activity. However, the ability of this chimera to bind phospholipase C gamma was severely impaired in comparison with the ability of the wild-type receptor, while the association with other cellular proteins was not affected. Further deletion of 35 residues, including Tyr-977, nearly abolished all PDGF-R cytoplasmic-domain biological signaling activities. None of the three C-terminal truncations completely abolished the mitogenic potential of the receptors or had any influence on ligand binding or receptor down regulation. Together, these data implicate the 80 C-terminal-most residues of the PDGF-R, and possibly Tyr-989, in phospholipase C gamma binding, while receptor sequences upstream from Asp-988 appear to be essential for specific interactions with other cellular polypeptides such as ras GTPase-activating protein and phosphatidylinositol 3-kinase. Thus, the mutants described here allow the separation of distinct PDGF-activated signaling pathways and demonstrate that phospholipase C gamma phosphorylation is not required for mitogenesis and transformation. PMID- 1406628 TI - Promoter-specific trans-activation by the adenovirus E1A12S product involves separate E1A domains. AB - Recent studies have shown that the adenovirus E1A12S product can trans-activate transcription by activating the transcription factor E2F. However, E2F cannot be the only target for the E1A12S product, since several cellular promoters have been found to be activated by the E1A12S protein even though they lack E2F sites. Indeed, we now show that activation of the hsp70 promoter by the E1A12S product requires the TATAA sequence. Moreover, activation of the hsp70 promoter requires the N-terminal domain of the E1A protein and does not require the conserved region 2 sequences which are required for the E2F-dependent activation of transcription. We conclude that the targeting of distinct transcription factors, leading to trans-activation of transcription of multiple promoters, involves distinct domains of the E1A proteins that are also required for oncogenic activity. PMID- 1406629 TI - Histone H2B gene transcription during Xenopus early development requires functional cooperation between proteins bound to the CCAAT and octamer motifs. AB - The ubiquitously expressed transcription factor Oct-1 and several other members of the POU domain protein family bind to a site, termed the octamer motif, that functions in the promoter and enhancer regions of a variety of genes expressed under diverse conditions. An octamer motif present in a conserved histone H2B specific promoter element is required for S-phase-specific transcription of mammalian histone H2B genes in cultured cells. We have previously shown that the octamer motif in a Xenopus histone H2B gene promoter was inactive in nondividing frog oocytes. Here we show that the octamer motif, in addition to regulatory elements (TATAA, CCAAT, and ATF motifs) that are active in oocytes, is required for maximal H2B gene transcription in developing frog embryos. Factors binding to each of the H2B upstream promoter elements are present in oocytes and increase slightly in abundance during early development. The activity of the H2B octamer motif in embryos is not specifically associated with increased binding by Oct-1 or the appearance of novel octamer-binding proteins but requires the presence of an intact CCAAT motif. Our results indicate that synergistic interactions among promoter-bound factors are important for octamer-dependent H2B transcription. We suggest that the activity of the H2B promoter is regulated primarily by changes in the interactions between proteins already bound to the promoter rather than by alterations in their intrinsic abilities to bind DNA. PMID- 1406630 TI - Selection of optimal kappa B/Rel DNA-binding motifs: interaction of both subunits of NF-kappa B with DNA is required for transcriptional activation. AB - Analysis of the p50 and p65 subunits of the NF-kappa B transcription factor complex has revealed that both proteins can interact with related DNA sequences through either homo- or heterodimer formation. In addition, the product of the proto-oncogene c-rel can bind to similar DNA motifs by itself or as a heterodimer with p50 or p65. However, these studies have used a limited number of known kappa B DNA motifs, and the question of the optimal DNA sequences preferred by each homodimer has not been addressed. Using purified recombinant p50, p65, and c-Rel proteins, optimal DNA-binding motifs were selected from a pool of random oligonucleotides. Alignment of the selected sequences allowed us to predict a consensus sequence for binding of the individual homodimeric Rel-related proteins, and DNA-protein binding analysis of the selected DNA sequences revealed sequence specificity of the proteins. Contrary to previous assumptions, we observed that p65 homodimers can interact with a subset of DNA sequences not recognized by p50 homodimers. Differential binding affinities were also obtained with p50- and c-Rel-selected sequences. Using either a p50- or p65-selected kappa B motif, which displayed differential binding with respect to the other protein, little to no binding was observed with the heterodimeric NF-kappa B complex. Similarly, in transfection experiments in which the selective kappa B binding sites were used to drive the expression of a chloramphenicol acetyltransferase reporter construct, the p65- and p50-selected motifs were activated only in the presence of p65 and p50/65 (a chimeric protein with the p50 DNA binding domain and p65 activation domain) expression vectors, respectively, and neither demonstrated a significant response to stimuli that induce NF-kappa B activity. These findings demonstrate that interaction of both subunits of the heterodimeric NF-kappa B complex with DNA is required for DNA binding and transcriptional activation and suggest that transcriptional activation mediated by the individual rel-related proteins will differ dramatically, depending on the specific kappa B motifs present. PMID- 1406631 TI - Ectopic recombination within homologous immunoglobulin mu gene constant regions in a mouse hybridoma cell line. AB - We have transferred a pSV2neo vector containing the wild-type constant region of the immunoglobulin mu gene (C mu) into the mutant hybridoma igm482, which bears a 2-bp deletion in the third constant-region exon of its haploid chromosomal mu gene (C mu 3). Independent igm482 transformants contain the wild-type immunoglobulin C mu region stably integrated in ectopic chromosomal positions. We report here that the wild-type immunoglobulin C mu region can function as the donor sequence in a gene conversion event which corrects the 2-bp deletion in the mutant igm482 chromosomal C mu 3 exon. The homologous recombination event restores normal immunoglobulin M production in the mutant cell. PMID- 1406632 TI - RPC82 encodes the highly conserved, third-largest subunit of RNA polymerase C (III) from Saccharomyces cerevisiae. AB - RNA polymerase C (III) promotes the transcription of tRNA and 5S RNA genes. In Saccharomyces cerevisiae, the enzyme is composed of 15 subunits, ranging from 160 to about 10 kDa. Here we report the cloning of the gene encoding the 82-kDa subunit, RPC82. It maps as a single-copy gene on chromosome XVI. The UCR2 gene was found in the opposite orientation only 340 bp upstream of the RPC82 start codon, and the end of the SKI3 coding sequence was found only 117 bp downstream of the RPC82 stop codon. The RPC82 gene encodes a protein with a predicted M(r) of 73,984, having no strong sequence similarity to other known proteins. Disruption of the RPC82 gene was lethal. An rpc82 temperature-sensitive mutant, constructed by in vitro mutagenesis of the gene, showed a deficient rate of tRNA relative to rRNA synthesis. Of eight RNA polymerase C genes tested, only the RPC31 gene on a multicopy plasmid was capable of suppressing the rpc82(Ts) defect, suggesting an interaction between the polymerase C 82-kDa and 31-kDa subunits. A group of RNA polymerase C-specific subunits are proposed to form a substructure of the enzyme. PMID- 1406633 TI - Retroviral insertions downstream of the heterogeneous nuclear ribonucleoprotein A1 gene in erythroleukemia cells: evidence that A1 is not essential for cell growth. AB - A large number of novel cellular proto-oncogenes have been identified and cloned by analysis of common integration sites in retrovirally induced malignancies. In the multistage erythroleukemias induced by the various strains of Friend leukemia virus, the analysis of proviral-integration events has led to the identification of two genes, Fli-1 and Spi-1, both novel members of the ets oncogene family of transcription factors. In this report, we describe the identification of another integration site, designated Fli-2 (Friend leukemia virus integration-2), in an erythroleukemia cell line induced by Friend murine leukemia virus (F-MuLV). Rearrangements at the Fli-2 locus were found in two erythroleukemia cell lines independently induced by F-MuLV and one leukemic cell line derived from the spleen of a mouse infected with the polycythemia strain of Friend leukemia virus. The deduced amino acid sequence of a cDNA corresponding to a transcript originating from genomic DNA adjacent to Fli-2 is identical to that of the human heterogeneous nuclear ribonucleoprotein A1 gene, a member of the gene family of RNA-binding proteins involved in RNA splicing. In one erythroleukemia cell line, A1 expression was undetectable as a result of F-MuLV integration in one allele and loss of the other allele. These results suggest that perturbations in RNA splicing mechanisms may contribute to malignant transformation and provide direct evidence that the A1 protein is not required for cell growth. PMID- 1406634 TI - Accumulation of U14 small nuclear RNA in Saccharomyces cerevisiae requires box C, box D, and a 5', 3' terminal stem. AB - U14 is one of several nucleolar small nuclear RNAs required for normal processing of rRNA. Functional mapping of U14 from Saccharomyces cerevisiae has yielded a number of mutants defective in U14 accumulation or function. In this study, we have further defined three structural elements required for U14 accumulation. The essential elements include the U14-conserved box C and box D sequences and a 5', 3' terminal stem. The box elements are coconserved among several nucleolar small nuclear RNAs and have been implicated in binding of the protein fibrillarin. New mutational results show that the first GA bases of the box C sequence UGAUGA are essential, and two vital bases in box D have also been identified. An intragenic suppressor of a lethal box C mutant has been isolated and shown to contain a new box C-like PyGAUG sequence two bases upstream of normal box C. The importance of the terminal stem was confirmed from new compensatory base changes and the finding that accumulation defects in the box elements can be complemented by extending the terminal stem. The results suggest that the observed defects in accumulation reflect U14 instability and that protein binding to one or more of these elements is required for metabolic stability. PMID- 1406635 TI - A CD44-like endothelial cell transmembrane glycoprotein (GP116) interacts with extracellular matrix and ankyrin. AB - We used complementary biochemical and immunological techniques to establish that an endothelial cell transmembrane glycoprotein, GP116, is a CD44-like molecule and binds directly both to extracellular matrix components (e.g., hyaluronic acid) and to ankyrin. The specific characteristics of GP116 are as follows: (i) GP116 can be surface labeled with Na 125I and contains a wheat germ agglutinin binding site(s), indicating that it has an extracellular domain; (ii) GP116 displays immunological cross-reactivity with a panel of CD44 antibodies, shares some peptide similarity with CD44, and has a similar 52-kDa precursor molecule, indicating that it is a CD44-like molecule; (iii) GP116 displays specific hyaluronic acid-binding properties, indicating that it is a hyaluronic acid receptor; (iv) GP116 can be phosphorylated by endogenous protein kinase C activated by 12-O-tetradecanoylphorbol-13-acetate and by exogenously added protein kinase C; and (v) GP116 and a 20-kDa tryptic polypeptide fragment of GP116 from the intracellular domain are capable of binding the membrane cytoskeleton linker molecule, ankyrin. Furthermore, phosphorylation of GP116 by protein kinase C significantly enhances GP116 binding to ankyrin. Together, these findings strongly suggest that phosphorylation of the transmembrane glycoprotein GP116 (a CD44-like molecule) by protein kinase C is required for effective GP116 ankyrin interaction during endothelial cell adhesion events. PMID- 1406636 TI - Mapping of epidermal growth factor-, serum-, and phorbol ester-responsive sequence elements in the c-jun promoter. AB - Expression of the nuclear proto-oncogene c-jun is rapidly and transiently induced by many growth factors, serum, and tumor promoters. The sequence elements in the c-jun promoter involved in serum or growth factor induction have not been identified. The c-jun promoter region between -117 and -72 contains binding sites for the transcription factors Sp1, CTF, and AP-1. An additional sequence element has been noted at position -59. This A+T-rich sequence, formerly proposed as a TFIID-binding site, conforms to the consensus binding sequence of a recently identified factor, RSRF (related to serum response factor). In this study, we mapped the sequences in the c-jun promoter responsible for epidermal growth factor (EGF), serum, and 12-O-tetradecanoylphorbol-13-acetate (TPA) induction by deletion and point mutational analysis. We found that the c-jun RSRF site is an important element for EGF and serum induction of the promoter and that there are several factors in HeLa nuclear extracts which specifically bind to this site. The RSRF site was also sufficient for EGF, serum, and TPA induction when assayed on a heterologous promoter. The c-jun AP-1 site was not required for EGF, serum, or TPA induction but was sufficient to mediate a weak response to these agents when assayed on a heterologous promoter. Double mutation of the RSRF and AP-1 sites suggests that there is an additional TPA-responsive element between -80 and +150 in the c-jun promoter. PMID- 1406637 TI - Modulation of interferon signaling in human fibroblasts by phorbol esters. AB - Phorbol esters activate the expression of a variety of early-response genes through protein kinase C-dependent pathways. In addition, phorbol esters may promote cell growth by the inhibition of expression of cellular gene products regulated by antiproliferative agents such as interferons (IFN)s. In human diploid fibroblasts, phorbol 12-myristate 13-acetate (PMA) selectively inhibits the IFN-alpha-induced cellular gene ISG54. Using transient transfection assays, we have delineated two elements in the promoter of this gene that are necessary for the inhibitory actions of PMA. These elements include (i) the IFN-stimulated response element (ISRE) which is necessary for IFN-alpha-induced cellular gene expression, and (ii) an element located near the site of transcription initiation. IFN-alpha treatment resulted in the rapid induction of ISGF3, a multisubunit transcription factor which binds to the ISRE. PMA caused a substantial reduction in IFN alpha-induced ISGF3 in both nuclear and cytoplasmic extracts, as determined by electrophoretic mobility shift assays with the ISRE as a probe. In vitro reconstitution experiments revealed that IFN-alpha activation of the ISGF3 alpha component of ISGF3 was not affected by PMA. Further experiments were consistent with the possibility that PMA regulated the activity of a cellular factor which competed with ISGF3 gamma for binding of the activated ISGF3 alpha polypeptides. Electrophoretic mobility shift assays using the cap site of ISG54 as a probe demonstrated the formation of a specific complex whose DNA binding activity was not affected by treatment of cells with PMA or IFN alpha. Competitive inhibition studies were consistent with the DNA-protein complex at the cap site of ISG54 containing proteins with DNA binding sites in common with those which also interact with the ISRE. These data suggest a unique regulatory mechanism by which phorbol esters can modulate IFN signaling. PMID- 1406638 TI - A bipartite suppressor: conjunction of two distinct factor-binding sites is essential for down-regulation in rat epoxide hydrolase gene expression. AB - We describe a novel transcriptional suppressor element found in the control region of the gene that encodes rat microsomal epoxide hydrolase (mEH), an inducible xenobiotic metabolizing enzyme. This element consists of the juxtaposition of two distinct factor-binding regions. The first region is composed of a series of five tandemly repeated factor-binding sequences, and the second region is an unique AT-rich factor-binding sequence. Although each region binds its cognate factor(s) in vitro, a single region does not function as a suppressor independently of the other. Transcriptional suppression was observed only when the two regions were combined. Thus, we propose that this regulatory element is a bipartite suppressor, requiring two distinct factor-binding regions for its function. The element displayed position-independent but orientation dependent suppressor activity. The level of suppressor activity was proportional to the number of repetitive sites in region 1. We speculate that this region could mediate the dose-response behavior of mEH gene expression induced by chemical carcinogens in vivo. A qualitative difference in the region 2 binding factor(s) was observed between normal liver cells and a hepatoma cell line or carcinogen-treated liver cells. The possible relationship between this observation and the deregulation of mEH gene expression during the course of hepatocarcinogenesis is discussed. PMID- 1406640 TI - The posttranslational processing of ras p21 is critical for its stimulation of yeast adenylate cyclase. AB - Mammalian ras genes substitute for the yeast RAS gene, and their products activate adenylate cyclase in yeast cells, although the direct target protein of mammalian ras p21s remains to be identified. ras p21s undergo posttranslational processing, including prenylation, proteolysis, methylation, and palmitoylation, at their C-terminal regions. We have previously reported that the posttranslational processing of Ki-ras p21 is essential for its interaction with one of its GDP/GTP exchange proteins named smg GDS. In this investigation, we have studied whether the posttranslational processing of Ki- and Ha-ras p21s is critical for their stimulation of yeast adenylate cyclase in a cell-free system. We show that the posttranslationally fully processed Ki- and Ha-ras p21s activate yeast adenylate cyclase far more effectively than do the unprocessed proteins. The previous and present results suggest that the posttranslational processing of ras p21s is important for their interaction not only with smg GDS but also with the target protein. PMID- 1406639 TI - Involvement of the SIN4 global transcriptional regulator in the chromatin structure of Saccharomyces cerevisiae. AB - We have cloned and sequenced the SIN4 gene and determined that SIN4 is identical to TSF3, identified as a negative regulator of GAL1 gene transcription (S. Chen, R.W. West, Jr., S.L. Johnson, H. Gans, and J. Ma, submitted for publication). Yeast strains bearing a sin4 delta null mutation have been constructed and are temperature sensitive for growth and display defects in both negative and positive regulation of transcription. Transcription of the CTS1 gene is reduced in sin4 delta mutants, suggesting that Sin4 functions as a positive transcriptional regulator. Additionally, a Sin4-LexA fusion protein activates transcription from test promoters containing LexA binding sites. The sin4 delta mutant also shows phenotypes common to histone and spt mutants, including suppression of delta insertion mutations in the HIS4 and LYS2 promoters, expression of promoters lacking upstream activation sequence elements, and decreased superhelical density of circular DNA molecules. These results suggest that the sin4 delta mutation may alter the structure of chromatin, and these changes in chromatin structure may affect transcriptional regulation. PMID- 1406641 TI - Effects of p56lck deficiency on the growth and cytolytic effector function of an interleukin-2-dependent cytotoxic T-cell line. AB - The growth, differentiation, and functional activities of antigen-stimulated T lymphocytes are regulated by the interaction of the T-cell-derived cytokine, interleukin-2 (IL-2), with the high-affinity IL-2 receptor (IL-2R). IL-2R occupancy initiates a rapid increase in intracellular protein tyrosine phosphorylation, suggesting that a receptor-coupled protein tyrosine kinase (PTK) serves as a proximal signaling element for the IL-2R. Previous studies implicated the src-family kinase, p56lck, as a potential IL-2R-linked signal transducer. In this study, we have characterized a spontaneous variant of the IL-2-dependent cytotoxic T-cell line, CTLL-2, which contains no detectable lck-derived mRNA transcripts, protein, or PTK activity. The p56lck-deficient CTLL-2 cells retained strict dependence on IL-2 for both viability and growth, indicating that p56lck activity was not required for the transduction of IL-2-mediated mitogenic signals. However, the p56lck-deficient cells exhibited a moderate decrease in their rate of IL-2-dependent proliferation. In contrast to this relatively modest proliferative defect, the p56lck-deficient cell line displayed a profound reduction in T-cell antigen receptor-dependent cytolytic effector functions. Both the proliferative and the cytolytic defects observed in the p56lck-deficient cells were completely reversed by transfection of these cells with a wild-type lck expression vector. These results indicate that p56lck expression is not obligatory for IL-2-mediated T-cell growth stimulation; however, this PTK plays a central role in the generation T-cell-mediated cytotoxic responses. PMID- 1406643 TI - Cutinase in Cryphonectria parasitica, the chestnut blight fungus: suppression of cutinase gene expression in isogenic hypovirulent strains containing double stranded RNAs. AB - Plant-pathogenic fungi produce cutinase, an enzyme required to degrade plant cuticles and facilitate penetration into the host. The absence of cutinase or a decrease in its production has been associated with a decrease in pathogenicity of the fungus. A set of isogenic strains of Cryphonectria parasitica, the chestnut blight fungus, was tested for the presence and amounts of cutinase activity. The virulent strain of C. parasitica produced and secreted significantly higher amounts of cutinase than the hypovirulent strains. Use of both nucleic acid and polyclonal antibody probes for cutinase from Fusarium solani f. sp. pisi showed that cutinase in C. parasitica is 25 kDa in size and is coded by a 1.1-kb mRNA. Both mRNA and protein were inducible by cutin hydrolysate, while hypovirulence agents suppressed the level of mRNA and the enzyme. Since all the strains had the cutinase gene, the suppression of expression was due to the hypovirulence agents. The data presented are the first report indicating that hypovirulence agents in C. parasitica regulate a gene associated with pathogenicity in other plant-pathogenic fungi. PMID- 1406642 TI - Examination of the DNA-binding ability of estrogen receptor in whole cells: implications for hormone-independent transactivation and the actions of antiestrogens. AB - We describe an assay employing the competitive binding of estrogen receptor (ER) with basal transcription factors on a constitutive promoter (cytomegalovirus hormone response element[s]-chloramphenicol acetyltransferase [CMV-(HRE)n-CAT, containing a hormone response element(s) between the TATA box and the start site of transcription]) to examine the DNA-binding ability of the human ER in whole cells. We used this promoter interference assay to examine the DNA binding of ER in cell lines containing high and low levels of endogenous ER, as well as in CHO cells expressing wild-type and mutant ERs from cotransfected expression vectors. The ER is capable of binding to the promoter interference constructs in the absence of added ligand, and estrogen (estradiol) or antiestrogen (trans hydroxytamoxifen or ICI 164,384) enhances or stabilizes this interaction. The binding of unoccupied ER to reporter gene activation plasmids results in ligand independent transactivation, presumably due to the TAF-1 function of the receptor. DNA binding of ER in the absence of ligand is observed in cells containing endogenous ER, or expressed ER, and occurs in cells with high or low receptor contents. Although estrogen- and antiestrogen-occupied ER complexes bind to DNA and reduce the template promoter activity, the extent of suppression achieved by ICI-bound ERs is consistently less than that achieved with the other ligands, presumably caused by the fact that ICI rapidly reduces the level of ER in most of the cells examined. However, the ICI-ER complexes that remain are in sufficient quantity to bind to gene activation reporter constructs, and in these cells, ICI still behaves as a pure antagonist of gene transcription and does not activate reporter genes. Hence, obstruction of ER DNA binding or reduction of ER in target cells may contribute to, but cannot fully explain, the pure antagonist character of the antiestrogen ICI 164,384. In addition, DNA binding by the ER alone is clearly not sufficient for ensuring full activation of transcription and argues for an intermediate in the receptor activation of promoters. PMID- 1406644 TI - Purification of splicing factor SF1, a heat-stable protein that functions in the assembly of a presplicing complex. AB - Splicing factor SF1 represents one of the proteins that function early in the splicing of nuclear pre-mRNA in the formation of a presplicing complex. SF1 was purified to homogeneity from HeLa cell nuclear extracts by column chromatography. It consists of a single polypeptide of 75 kDa and is distinct from other protein factors that function early in spliceosome assembly. SF1 activity is completely resistant to temperatures of up to 100 degrees C. The purified protein does not appear to be associated with RNA-binding, RNA-annealing, or ATPase activity. PMID- 1406646 TI - Distinct roles for the two cGATA-1 finger domains. AB - We have generated and analyzed by functional assays mutations of the chicken erythroid transcription factor GATA-1. The cGATA-1 protein contains two related finger domains highly conserved across species and characteristic of the family of GATA-binding factors. We find that mutations in the C-terminal finger or adjacent basic region abolish sequence-specific DNA binding, confirming that this region constitutes a novel DNA-binding domain sufficient to recognize the consensus WGATAR motif. At least three separate regions outside of this finger II domain contribute in a cooperative manner to the trans-activation potential of the protein. As expected from previous results analyzing the mouse homolog, we find that the N-terminal finger plays a role in DNA binding by affecting the stability of the DNA-protein complex. In addition, we find mutations of finger I subtly altered in DNA-binding function which greatly diminish trans-activation. Our results support the notion that the GATA-1 protein must be positioned precisely on the GATA cis element to enable the activation of target genes. PMID- 1406645 TI - Mutations in the WSAWSE and cytosolic domains of the erythropoietin receptor affect signal transduction and ligand binding and internalization. AB - The terminal development of erythroid progenitor cells is promoted in part through the interaction of erythropoietin (EPO) with its cell surface receptor. This receptor and a growing family of related cytokine receptors share homologous extracellular features, including a well-conserved WSXWS motif. To explore the functional significance of this motif in the murine EPO receptor, five WSAWSE mutants were prepared and their signal-transducing, ligand binding, and endocytotic properties were compared. EPO receptors mutated at tryptophan residues (W-232, W-235----G; W-235----G; W-235----F) failed to mediate EPO induced growth or pp100 phosphorylation, while S-236----T and E-237----K mutants exhibited partial to full activity (50 to 100% of wild-type growth and induced phosphorylation). Ligand affinity was reduced for mutant receptors (two- to fivefold), yet expression at the cell surface for all receptors was nearly equivalent. Also, the ability of mutated receptors to internalize ligand was either markedly reduced or abolished (W-235----F), indicating a role for the WSAWSE region in hormone internalization. Interestingly, receptor forms lacking 97% of the cytosolic domain (no signal-transducing capacity; binding affinity reduced two- to threefold) internalized EPO efficiently. This and all WSAWSE receptor forms studied also mediated specific cross-linking of 125I-EPO to three accessory membrane proteins (M(r)s, 120,000, 105,000, and 93,000). These findings suggest that the WSAWSE domain of the EPO receptor is important for EPO-induced signal transduction and ligand internalization. In contrast, although the cytosolic domain is required for growth signaling, it appears nonessential for efficient endocytosis. PMID- 1406647 TI - In vivo transcriptional analysis of the TATA-less promoter of the Drosophila melanogaster vermilion gene. AB - Transcriptional regulation of the TATA-less promoter of the Drosophila melanogaster vermilion (v) gene was investigated. Developmental Northern (RNA) blot analysis showed that v transcripts accumulate during late embryo, larval, and adult stages. Sequences that control expression in adults were delineated by analyzing a series of 5' and 3' deletion constructions after germ line transformation. These studies defined two regions, -300 to -600 and -60 to -160, relative to the major transcription start site, as important for maximal levels of expression. Analysis of transformants bearing v-lacZ promoter fusions showed that larval expression is fat body specific and that expression depends on sequences located between +19 and +36 downstream of transcription start site. This downstream element can be functionally replaced by a TATA box in vivo. Furthermore, when added to the wild-type v promoter, a TATA element augments the level of v transcription by three- to fivefold. PMID- 1406648 TI - Multiple elements in the upstream glucokinase promoter contribute to transcription in insulinoma cells. AB - beta-cell type-specific expression of the upstream glucokinase promoter was studied by transfection of fusion genes and analysis of DNA-protein interactions. A construct containing 1,000 bp of 5'-flanking DNA was efficiently expressed in HIT M2.2.2 cells, a beta-cell-derived line that makes both insulin and glucokinase, but not in NIH 3T3 cells, a heterologous cell line. In a series of 5' deletion mutations between bases -1000 and -100 (relative to a base previously designated +1), efficient expression in HIT cells was maintained until -280 bp, after which transcription decreased in a stepwise manner. The sequences between 180 and -1 bp contributing to transcriptional activity in HIT cells were identified by studying 28 block transversion mutants that spanned this region in 10-bp steps. Two mutations reduced transcription 10-fold or more, while six reduced transcription between 3- and 10-fold. Three mutationally sensitive regions of this promoter were found to bind to a factor that was expressed preferentially in pancreatic islet beta cells. The binding sites, designated upstream promoter elements (UPEs), shared a consensus sequence of CAT(T/C)A(C/G). Methylation of adenine and guanine residues within this sequence prevented binding of the beta-cell factor, as did mutations at positions 2, 3, and 5. Analysis of nuclear extracts from different cell lines identified UPE-binding activity in HIT M2.2.2 and beta-TC-3 cells but not in AtT-20, NIH 3T3, or HeLa cells; the possibility of a greatly reduced amount in alpha-TC-6 cells could not be excluded. UV laser cross-linking experiments supported the beta-cell type expression of this factor and showed it to be approximately 50 kDa in size. Gel mobility shift competition experiments showed that this beta-cell factor is the same that binds to similar elements, termed CT boxes, in the insulin promoter. Thus, a role for these elements (UPEs or CT boxes), and the beta-cell factor that binds to them, in determining the expression of genes in the beta cells of pancreatic islets is suggested. PMID- 1406649 TI - Sequences in the human c-myc P2 promoter affect the elongation and premature termination of transcripts initiated from the upstream P1 promoter. AB - A conditional block to transcription elongation provides one mechanism for controlling the steady-state levels of c-myc RNA in mammalian cells. Although prematurely terminated c-myc RNAs are not detectable in mammalian cells, truncated c-myc RNAs with 3' ends that map near the end of the first exon are transcribed from human c-myc templates injected into Xenopus oocytes germinal vesicles. A series of linker scanner and deletion mutants within the c-myc P2 promoter was tested in the Xenopus oocyte injection assay to determine the potential contribution of promoter elements to the elongation or premature termination of c-myc transcription. Although this analysis failed to identify sequences in the P2 promoter that significantly affect the elongation or termination of P2-initiated transcripts, our results suggest that sequences within the P2 promoter contribute to the premature termination of transcripts initiated at the upstream P1 promoter. A subset of these sequences is essential for the efficient elongation of P1-initiated transcripts through intrinsic sites of termination at the end of exon 1. These sequences affect P1 elongation when they are downstream of the site of initiation, and we hypothesize that they may be analogous to a class of prokaryotic elements required for antitermination. PMID- 1406651 TI - Downregulation of JE and KC genes by glucocorticoids does not prevent the G0--- G1 transition in BALB/3T3 cells. AB - The effects of glucocorticoid hormones on the expression of the growth factor inducible genes JE, KC, and c-myc were analyzed in parental BALB/3T3 and polyomavirus middle-T antigen-transfected cell lines. Northern (RNA) blot hybridization and run-on transcription analysis showed that (i) glucocorticoid hormones selectively inhibit JE and KC expression at the transcriptional level and (ii) the downregulatory effect of glucocorticoids on JE and KC expression is partial for serum-stimulated and middle T antigen-transformed cells and total for quiescent and exponentially growing cells. Gel mobility assays using AP-1 oligonucleotides showed a positive correlation between glucocorticoid downregulating effect and presence of the AP-1 complex. JE and KC downregulation by means of the AP-1 complex may play a role in the actions of glucocorticoids as anti-inflammatory and antitumor agents. The ability of glucocorticoids to downregulate JE and KC was used to investigate the relevance of these genes to the mitogenic response to serum growth factors. Hydrocortisone did not alter the basal DNA synthesis level displayed by quiescent 3T3 cells, but it potentiated both the mitogenic effect of platelet-derived growth factor and c-myc induction by serum growth factors. Upon serum restimulation, untreated and dexamethasone treated quiescent 3T3 cultures entered the S phase after an identical time lag (G1). These results suggest that (i) JE and KC are not necessary for the G0----G1 ---S transition and (ii) c-myc overexpression is likely to be the basis for the potentiating effect of glucocorticoids on serum growth factors. PMID- 1406650 TI - The yeast EUG1 gene encodes an endoplasmic reticulum protein that is functionally related to protein disulfide isomerase. AB - The product of the EUG1 gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein with homology to both the mammalian protein disulfide isomerase (PDI) and the yeast PDI homolog encoded by the essential PDI1 gene. Deletion or overexpression of EUG1 causes no growth defects under a variety of conditions. EUG1 mRNA and protein levels are dramatically increased in response to the accumulation of native or unglycosylated proteins in the endoplasmic reticulum. Overexpression of the EUG1 gene allows yeast cells to grow in the absence of the PDI1 gene product. Depletion of the PDI1 protein in Saccharomyces cerevisiae causes a soluble vacuolar glycoprotein to accumulate in its endoplasmic reticulum form, and this phenotype is only partially relieved by the overexpression of EUG1. Taken together, our results indicate that PDI1 and EUG1 encode functionally related proteins that are likely to be involved in interacting with nascent polypeptides in the yeast endoplasmic reticulum. PMID- 1406652 TI - Characterization of the human lipoprotein lipase (LPL) promoter: evidence of two cis-regulatory regions, LP-alpha and LP-beta, of importance for the differentiation-linked induction of the LPL gene during adipogenesis. AB - When preadipocytes differentiate into adipocytes, several differentiation-linked genes are activated. Lipoprotein lipase (LPL) is one of the first genes induced during this process. To investigate early events in adipocyte development, we have focused on the transcriptional activation of the LPL gene. For this purpose, we have cloned and fused different parts of intragenic and flanking sequences with a chloramphenicol acetyltransferase reporter gene. Transient transfection experiments and DNase I hypersensitivity assays indicate that several positive as well as negative elements contribute to transcriptional regulation of the LPL gene. When reporter gene constructs were stably introduced into preadipocytes, we were able to monitor and compare the activation patterns of different promoter deletion mutants at selected time points representing the process of adipocyte development. We could delimit two cis-regulatory elements important for gradual activation of the LPL gene during adipocyte development in vitro. These elements, LP-alpha (-702 to -666) and LP-beta (-468 to -430), contain a striking similarity to a consensus sequence known to bind the transcription factors HNF-3 and fork head. Results of gel mobility shift assays and DNase I and exonuclease III in vitro protection assays indicate that factors with DNA-binding properties similar to those of the HNF-3/fork head family of transcription factors are present in adipocytes and interact with LP-alpha and LP-beta. We also demonstrate that LP alpha and LP-beta were both capable of conferring a differentiation-linked expression pattern to a heterolog promoter, thus mimicking the expression of the endogenous LPL gene during adipocyte differentiation. These findings indicate that interactions with LP-alpha and LP-beta could be a part of a differentiation switch governing induction of the LPL gene during adipocyte differentiation. PMID- 1406653 TI - Localization of the rap1GAP catalytic domain and sites of phosphorylation by mutational analysis. AB - rap1GAP is a GTPase-activating protein that specifically stimulates the GTP hydrolytic rate of p21rap1. We have defined the catalytic domain of rap1GAP by constructing a series of cDNAs coding for mutant proteins progressively deleted at the amino- and carboxy-terminal ends. Analysis of the purified mutant proteins shows that of 663 amino acid residues, only amino acids 75 to 416 are necessary for full GAP activity. Further truncation at the amino terminus resulted in complete loss of catalytic activity, whereas removal of additional carboxy terminal residues dramatically accelerated the degradation of the protein in vivo. The catalytic domain we have defined excludes the region of rap1GAP which undergoes phosphorylation on serine residues. We have further defined this phosphoacceptor region of rap1GAP by introducing point mutations at specific serine residues and comparing the phosphopeptide maps of the mutant proteins. Two of the sites of phosphorylation by cyclic AMP (cAMP)-dependent kinase were localized to serine residues 490 and 499, and one site of phosphorylation by p34cdc2 was localized to serine 484. In vivo, rap1GAP undergoes phosphorylation at four distinct sites, two of which appear to be identical to the sites phosphorylated by cAMP-dependent kinase in vitro. PMID- 1406654 TI - Transgenic overexpression of transforming growth factor alpha bypasses the need for c-Ha-ras mutations in mouse skin tumorigenesis. AB - The induction of skin papillomas in mice can be divided into two different stages. Chemical initiation frequently elicits mutations in the Ha-ras gene, leading to the constitutive activation of ras. The second step, promotion, involves repetitive topical application of phorbol esters or wounding, leading to epidermal hyperproliferation and papilloma formation. We have found that overexpression of transforming growth factor alpha (TGF-alpha) in the basal epidermal layer of transgenic mice yielded papillomas directly upon wounding or 12-O-tetradecanoylphorbol-13-acetate treatment without the need for an initiator. Moreover, papillomas from TGF-alpha mice did not exhibit mutations in the Ha-ras gene. Interestingly, TGF-alpha acted synergistically with 12-O tetradecanoylphorbol-13-acetate to enhance epidermal hyperproliferation. Our results demonstrate a central role for TGF-alpha overexpression in tumorigenesis and provide an important animal model for the study of skin tumorigenesis. PMID- 1406655 TI - Interactions among LRF-1, JunB, c-Jun, and c-Fos define a regulatory program in the G1 phase of liver regeneration. AB - In regenerating liver, a physiologically normal model of cell growth, LRF-1, JunB, c-Jun, and c-Fos among Jun/Fos/LRF-1 family members are induced posthepatectomy. In liver cells, high levels of c-Fos/c-Jun, c-Fos/JunB, LRF-1/c Jun, and LRF-1/JunB complexes are present for several hours after the G0/G1 transition, and the relative level of LRF-1/JunB complexes increases during G1. We provide evidence for dramatic differences in promoter-specific activation by LRF-1- and c-Fos-containing complexes. LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. LRF-1/c-Jun, c-Fos/c-Jun, and c-Fos/JunB activate specific AP-1 and ATF site-containing promoters, and in contrast, LRF 1/JunB potently represses c-Fos- and c-Jun-mediated activation of these promoters. Repression is dependent on a region in LRF-1 that includes amino acids 40 to 84 (domain R) and the basic/leucine zipper domain. As the relative level of LRF-1/JunB complexes increases posthepatectomy, c-Fos/Jun-mediated ATF and AP-1 site activation is likely to decrease with simultaneous transcriptional activation of the many liver-specific genes whose promoters contain cyclic AMP response element sites. Thus, through complex interactions among LRF-1, JunB, c Jun, and c-Fos, control of delayed gene expression may be established for extended times during the G1 phase of hepatic growth. PMID- 1406657 TI - Localization of a DNA replication origin and termination zone on chromosome III of Saccharomyces cerevisiae. AB - Two-dimensional gel electrophoretic replicon mapping techniques were used to identify all functional DNA replication origins and termini in a 26.5-kbp stretch in the left arm of yeast chromosome III. Only one origin was detected; it coincided with an ARS element (ARS306), as have all previously mapped yeast origins. A replication termination region was identified in a 4.3-kbp stretch at the telomere-proximal end of the investigated region, between the origin identified in this paper and the neighboring, previously mapped, ARS305 associated origin (previously called the A6C origin). Termination does not occur at a specific site; instead, it appears to be the consequence of replication forks converging in a stretch of DNA of at least 4.3 kbp. PMID- 1406656 TI - Regulation of collagen I gene expression by ras. AB - Although transformation of rodent fibroblasts can lead to dramatic changes in expression of extracellular matrix genes, the molecular basis and physiological significance of these changes remain poorly understood. In this study, we have investigated the mechanism(s) by which ras affects expression of the genes encoding type I collagen. Levels of both alpha 1(I) and alpha 2(I) collagen mRNAs were markedly reduced in Rat 1 fibroblasts overexpressing either the N-rasLys-61 or the Ha-rasVal-12 oncogene. In fibroblasts conditionally transformed with N rasLys-61, alpha 1(I) transcript levels began to decline within 8 h of ras induction and reached 1 to 5% of control levels after 96 h. In contrast, overexpression of normal ras p21 had no effect on alpha 1(I) or alpha 2(I) mRNA levels. Nuclear run-on experiments demonstrated that the transcription rates of both the alpha 1(I) and alpha 2(I) genes were significantly reduced in ras transformed cells compared with those in parental cells. In addition, the alpha 1(I) transcript was less stable in transformed cells. Chimeric plasmids containing up to 3.6 kb of alpha 1(I) 5'-flanking DNA and up to 2.3 kb of the 3' flanking region were expressed at equivalent levels in both normal and ras transformed fibroblasts. However, a cosmid clone containing the entire mouse alpha 1(I) gene, including 3.7 kb of 5'- and 4 kb of 3'-flanking DNA, was expressed at reduced levels in fibroblasts overexpressing oncogenic ras. We conclude that oncogenic ras regulates the type I collagen genes at both transcriptional and posttranscriptional levels and that this effect, at least for the alpha 1(I) gene, may be mediated by sequences located either within the body of the gene itself or in the distal 3'-flanking region. PMID- 1406658 TI - Molecular involvement of the pvt-1 locus in a gamma/delta T-cell leukemia bearing a variant t(8;14)(q24;q11) translocation. AB - A highly malignant human T-cell receptor (TCR) gamma/delta+ T-cell leukemia was shown to have a productive rearrangement of the TCR delta locus on one chromosome 14 and a novel t(8;14)(q24;q11) rearrangement involving the J delta 1 gene segment on the other chromosome 14. Chromosome walking coupled with pulsed-field gel electrophoretic (PFGE) analysis determined that the TCR J delta 1 gene fragment of the involved chromosome was relocated approximately 280 kb downstream of the c-myc proto-oncogene locus found on chromosome band 8q24. This rearrangement was reminiscent of the Burkitt's lymphoma variants that translocate to a region identified as the pvt-1 locus. Sequence comparison of the breakpoint junctions of interchromosomal rearrangements in T-cell leukemias involving the TCR delta-chain locus revealed novel signal-like sequence motifs, GCAGA(A/T)C and CCCA(C/G)GAC. These sequences were found on chromosome 8 at the 5' flanking site of the breakpoint junction of chromosome 8 in the TCR gamma/delta leukemic cells reported here and also on chromosome 1 in T-cell acute lymphocytic leukemia patients carrying the t(1;14)(p32;q11) rearrangement. These results suggest that (i) during early stages of gamma delta T-cell ontogeny, the region 280 kb 3' of the c-myc proto-oncogene on chromosome 8 is fragile and accessible to the lymphoid recombination machinery and (ii) rearrangements to both 8q24 and 1p32 may be governed by novel sequence motifs and be subject to common enzymatic mechanisms. PMID- 1406659 TI - Analysis of the defect in DNA end joining in the murine scid mutation. AB - Murine severe combined immune deficiency (scid) is marked by a 5,000-fold reduction in coding joint formation in V(D)J recombination of antigen receptors. Others have demonstrated a sensitivity to double-strand breaks generated by ionizing radiation and bleomycin. We were interested in establishing the extent of the defect in intramolecular and intermolecular DNA end joining in lymphoid and nonlymphoid cells from scid mice. We conducted a series of studies probing the ability of these cells to resolve free ends of linear DNA molecules having various biochemical end configurations. We find that the stable integration of linear DNA into scid fibroblasts is reduced 11- to 75-fold compared with that in normal fibroblasts. In contrast, intramolecular and intermolecular end joining occur at normal frequencies in scid lymphocytes and fibroblasts. This normal level of end joining is observed regardless of the type of overhang and regardless of the requirement for nucleolytic activities prior to ligation. The fact that free ends having a wide variety of end configurations are recircularized normally in scid cells rules out certain models for the defect in scid. We discuss the types of DNA end joining reactions that are and are not affected in this double-strand break repair defect in the context of a hairpin model for V(D)J recombination. PMID- 1406661 TI - cis-acting elements involved in the alternative translation initiation process of human basic fibroblast growth factor mRNA. AB - Four forms of basic fibroblast growth factor (bFGF) are synthesized from the same mRNA, resulting from alternative initiations of translation at three CUG start codons and one AUG start codon. The CUG- and AUG-initiated forms have distinct intracellular localizations and can modify cell phenotypes differently, indicating that control of the alternative expression of the different forms of bFGF has an important impact on the cell. In this study, we investigated the roles of the mRNA 5' untranslated region and the alternatively translated region located between the CUG and AUG codons in the regulation of alternative translation of the different forms of bFGF. Deletions and site-directed mutagenesis were carried out in bFGF mRNA leader, and translation was studied in vitro and in vivo. The results enabled us to identify five cis-acting RNA elements (two in the 5' untranslated region and three in the alternatively translated region) involved in the regulation of either global or alternative initiation of translation. Each of these elements had a specific effect on the level of synthesis of the different forms of bFGF. Furthermore, we showed that the 5' untranslated region regulatory elements had different effects on bFGF translation, depending on the translation system used. These results suggest that bFGF translation is modulated by cis-acting elements corresponding to secondary or tertiary RNA structures, which could be the targets of cell-specific trans acting factors. PMID- 1406660 TI - A proposed mechanism for promoter-associated DNA rearrangement events at a variant surface glycoprotein gene expression site. AB - The expressed variant cell surface glycoprotein (VSG) gene of the protozoan parasite Trypanosoma brucei is invariably found at one of several telomeric VSG gene expression sites (ESs). The active ES in variant 118 clone 1 is found on a 1.5-Mb chromosome, and the promoter region is located more than 45 kb upstream of the VSG gene. We had previously shown that DNA rearrangement events occurred in the promoter region, specifically at inactivation of this ES (K. M. Gottesdiener, H.-M. Chung, S. L. Brown, M. G.-S. Lee, and L. H. T. Van der Ploeg, Mol. Cell. Biol. 11:2467-2477, 1991). In this report, we describe the cloning of the entire 17-kb promoter region, which revealed the presence of two identical 2.15-kb tandem promoter repeats separated by 13 kb of DNA. The two virtually identical promoter repeats both function efficiently in directing transcription in transient transfection assays in insect-form trypanosomes. We characterized the DNA rearrangement events that occur at ES inactivation, and by studying both of the reciprocal products of this recombination event, we infer that these result from direct (promoter) repeat recombination, formation of heteroduplex DNA, and a reciprocal exchange event that releases a circular DNA as a side product of the reaction. The finding of DNA recombinational events in a region of the VSG gene ES that encodes the promoter(s), and their relatively frequent occurrence at ES inactivation, suggests a possible role in ES control. PMID- 1406662 TI - GAL11 protein, an auxiliary transcription activator for genes encoding galactose metabolizing enzymes in Saccharomyces cerevisiae. PMID- 1406663 TI - Identification of a novel dimer stabilization region in a plant bZIP transcription activator. AB - We have carried out deletion analyses of a tobacco transcription activator, TGA1a, in order to define its functional domains. TGA1a belongs to the basic region-leucine zipper (bZIP) class of DNA-binding proteins. Like other proteins of this class, it binds to its target DNA as a dimer, and its bZIP domain is necessary and sufficient for specific DNA binding. A mutant polypeptide containing the bZIP domain alone, however, shows a lower DNA-binding affinity than the full-length TGA1a. The C-terminal portion of TGA1a, which is essential for the higher DNA-binding affinity, contains a polypeptide region that can stabilize dimeric forms of the protein. This polypeptide region is designated the dimer stabilization (DS) region. Under our in vitro conditions, TGA1a derivatives with the DS region and those without the region do not form a detectable mixed dimer. This result indicates that in addition to the leucine zipper, the DS region can serve as another determinant of the dimerization specificity of TGA1a. In fact, the DS region, when fused to another bZIP protein, C/EBP, can inhibit dimer formation between the fusion protein and native C/EBP, whereas each of these can form homodimers. Such a portable determinant of dimerization specificity has potential application in studies of DNA-binding proteins as well as in biotechnology. PMID- 1406664 TI - A DNA element that regulates expression of an endogenous retrovirus during F9 cell differentiation is E1A dependent. AB - The retinoic acid-induced differentiation of F9 cells into parietal endoderm-like cells activates transcription of the endogenous mouse retrovirus, the intracisternal A-particle (IAP). To investigate the elements that control IAP gene differentiation-specific expression, we used methylation interference, Southwestern (DNA-protein), and transient-transfection assays and identified the IAP-proximal enhancer (IPE) element that directs differentiation-specific expression. We find that the IPE is inactive in undifferentiated F9 cells and active in differentiated parietal endoderm-like PYS-2 cells. Three proteins of 40, 60, and 68 kDa bind to the sequence GAGTAGAC located between nucleotides -53 and -47 within the IPE. The 40- and 68-kDa proteins from both the undifferentiated and differentiated cells exhibit similar DNA-binding activities. However, the 60-kDa protein from differentiated cells has greater binding activity than that from undifferentiated cells, suggesting a role for this protein in F9 differentiation-specific expression of the IAP gene. The IAP gene is negatively regulated by the adenovirus E1A proteins, and the E1A sequence responsible for repression is located at the N terminus, between amino acids 2 and 67. The DNA sequence that is the target of E1A repression also maps to the IPE element. Colocalization of the differentiation-specific and E1A-sensitive elements to the same protein-binding site within the IPE suggests that the E1A like activity functions in F9 cells to repress IAP gene expression. Activation of the IAP gene may result when the E1A-like activity is lost or inactivated during F9 cell differentiation, followed by binding of the 60-kDa positive regulatory protein to the enhancer element. PMID- 1406666 TI - Trypanosoma brucei spliced-leader RNA methylations are required for trans splicing in vivo. AB - The Trypanosoma brucei spliced leader (SL) RNA donates its 5' leader sequence to all nuclear pre-mRNAs via trans RNA splicing. The SL RNA is a small-nuclear U RNA like molecule which is present in the cell as part of a small ribonucleoprotein particle. However, unlike the trimethylguanosine-capped small nuclear U RNAs, the SL RNA has a highly modified 5' terminus containing an m7G cap and methylations on the first four transcribed nucleotides. Here, we show that incubation of procyclic-form T. brucei in the presence of the S-adenosylmethionine analog, sinefungin, leads to a rapid inhibition of SL RNA methylation. A concomitant inhibition of trans splicing and an accumulation of high-molecular-weight tubulin transcripts were also observed. The effects of sinefungin on SL RNA methylation and on trans splicing were correlated by labeling of cells incubated in the presence of the antibiotic. The results indicate that 5' modifications of the SL RNA are necessary for it to participate in trans splicing. SL RNA modification is not required for assembly of the core SL ribonucleoprotein, as these Cs2SO4 resistant particles can be formed with either methylated or undermethylated SL RNA. PMID- 1406665 TI - A mammalian factor that binds telomeric TTAGGG repeats in vitro. AB - We have identified a DNA-binding activity with specificity for the TTAGGG repeat arrays found at mammalian telomeres. This factor, called TTAGGG repeat factor (TRF), is present in nuclear extracts of human, mouse, and monkey cells. TRF from HeLa cells was characterized in detail by electrophoretic mobility shift assays. It binds double-stranded TTAGGG repeats in linear and circular DNAs. Single stranded repeats are not recognized. The optimal site for TRF appears to contain more than six contiguous TTAGGG repeats. Tandem arrays of TAGGG, TTTAGGG, TTTTAGGG, TTGGGG, and TTAGGC repeats do not bind TRF well, indicating that TRF preferentially recognizes the telomeric repeat sequence present at mammalian chromosome ends. The apparent molecular mass of this factor, based on recovery of TRF from sodium dodecyl sulfate-polyacrylamide gels, is approximately 50 kDa. We suggest that TRF binds along the length of mammalian telomeres. PMID- 1406668 TI - The osmotic integrity of the yeast cell requires a functional PKC1 gene product. AB - Seven temperature-sensitive cell lysis (cly) mutant strains of Saccharomyces cerevisiae were isolated which lyse at the restrictive temperature on hypotonic but not on osmotically supported medium. The seven mutants fell into four complementation groups, CLY12 to CLY15. The wild-type CLY15 gene was isolated by complementation of the cly15 temperature-sensitive growth defect. Sequence analysis revealed that the complementing DNA fragment encoded a partial PKC1 gene, which has previously been isolated as an S. cerevisiae homolog of mammalian protein kinase C genes (D. E. Levin, F. O. Fields, R. Kunisawa, J. M. Bishop, and J. Thorner, Cell 62:213-224, 1990). Subsequent genetic analysis showed that CLY15 and PKC1 represent identical loci in the yeast genome. A truncated PKC1 gene encoding only the predicted catalytic domain of Pkc1p was able to complement pkc1 mutant strains. Similar to what has been reported recently (D. E. Levin and E. Bartlett-Heubusch, J. Cell Biol. 116:1221-1229, 1992), we observed that cells deleted for the PKC1 gene are viable when grown on osmotically stabilized medium but are osmotically fragile and lyse rapidly after a shift to hypotonic medium. As shown by light and electron microscopic examinations, the delta pkc1 strain exhibits many cells with a strongly elongated bud or chains of incompletely budded cells when grown on solid medium. PMID- 1406667 TI - Elements responsible for hormonal control and tissue specificity of L-type pyruvate kinase gene expression in transgenic mice. AB - L-type pyruvate kinase (L-PK) is a key enzyme of the glycolytic pathway specifically expressed in the liver and, to a lesser degree, in the small intestine and kidney. One important characteristic of L-PK gene expression is its strong activation by glucose and insulin and its complete inhibition by fasting or glucagon treatment. Having previously established that the entire rat L-PK gene plus 3.2 kbp of 5'-flanking region functions in mice in a tissue-specific and hormonally regulated manner, various deletions of these 3.2 kbp of 5' flanking regions were tested in transgenic animals to map the cis-acting elements involved in transcriptional gene regulation. Our experiments indicate that the proximal region between -183 and +11 confers tissue specificity and contains all the information necessary for dietary and hormonal control of L-PK gene expression in vivo. We found, however, that the transcriptional activity generated by this proximal promoter fragment can be modulated by distal sequences in a tissue-specific manner. (i) Sequences between bp -183 and -392 seem to play a dual role in the liver and small intestine; they induce L-PK expression in the liver but repress it in the small intestine. (ii) Sequences from bp -392 up to 1170 do not seem to have any additional effect on promoter activity. (iii) Between bp -1170 and -2080, we found a putative extinguisher whose transcriptional inhibitory effect is much more marked in the small intestine than in the liver. (iv) Finally, between bp -2080 and -3200, we identified an activating sequence required for full expression of the gene in the liver. PMID- 1406669 TI - Phylogenetic footprinting reveals a nuclear protein which binds to silencer sequences in the human gamma and epsilon globin genes. AB - Tissue- and developmental stage-specific expression of the human beta-like globin genes is regulated by a combination of ubiquitous and erythroid-restricted trans factors that bind to cis elements near each of the five active genes. Additional interactions of these cis and trans factors with sequences located in the far 5' end of the cluster occur by as yet obscure mechanisms. Because of the complexity of this regulatory puzzle, precise identification of the determinants that control hemoglobin switching has proven difficult. Phylogenetic footprinting is an evolutionary approach to this problem which is based on the supposition that the basic mechanisms of switching are conserved throughout mammalian phylogeny. Alignment of the 5' flanking regions of the gamma genes of several species allows the identification of footprints of 100% conserved sequence. We have now tested oligomers spanning 13 such phylogenetic footprints and find that 12 are bound by nuclear proteins. One conserved element located at -1086 from the gamma genes exhibits repressor activity in transient transfection studies. The protein that binds this element, CSBP-1 (conserved sequence-binding protein 1), also binds at three sites within a silencer element upstream from the epsilon globin gene. Further analysis reveals that the CSBP-1 binding activity is identical to that of a recently cloned zinc finger protein that has been shown to act as a repressor in other systems. The binding of CSPB-1 to silencer sequences in the epsilon and gamma globin genes may be important in the stage-specific silencing of these genes. PMID- 1406670 TI - The EBNA2-related resistance towards alpha interferon (IFN-alpha) in Burkitt's lymphoma cells effects induction of IFN-induced genes but not the activation of transcription factor ISGF-3. AB - Transfection of a plasmid encoding the Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) gene confers resistance to the antiproliferative effect of alpha interferon (IFN-alpha) in EBV-negative U968 cells (P. Aman and A. von Gabain, EMBO J. 9:147-152, 1990). We studied the expression of IFN-stimulated genes (ISGs) in two pairs of Burkitt's lymphoma cell lines, differing in the expression of the putative immortalizing gene of EBV, EBNA2. In EBNA2-expressing cells, the induction of four ISGs by IFN-alpha was strongly reduced or, in some cases, abolished. Chloramphenicol acetyltransferase reporter gene constructs containing different IFN-stimulated response elements were transfected into EBNA2-negative and EBNA2-positive cells. Induction of chloramphenicol acetyltransferase activity by IFN was impaired in EBNA2-positive cells. Also, a reporter gene construct driven by an IFN-gamma-sensitive promoter element was affected. However, as revealed by gel shift assays, EBNA2-positive and EBNA2-negative cells exhibited a nearly identical pattern of IFN-stimulated response element-binding proteins. Most important, activation of the factor ISGF-3, which previously has been shown to be required and sufficient for transcriptional activation of IFN-induced genes, was not inhibited in IFN-resistant cells expressing EBNA2. The mechanism of the EBNA2-related IFN resistance seems to be distinct both from the resistance mediated by hepatitis virus and adenovirus gene products and from the IFN resistance in Daudi cell variants. In these three cases, the transcriptional block of IFN-induced genes is due to inhibition of ISGF-3 activation and binding. Our data suggest that the EBNA2-related IFN resistance in Burkitt's lymphoma cells acts downstream of the activation of ISGF-3. PMID- 1406671 TI - The 70-kilodalton adenylyl cyclase-associated protein is not essential for interaction of Saccharomyces cerevisiae adenylyl cyclase with RAS proteins. AB - In the yeast Saccharomyces cerevisiae, adenylyl cyclase is regulated by RAS proteins. We show here that the yeast adenylyl cyclase forms at least two high molecular-weight complexes, one with the RAS protein-dependent adenylyl cyclase activity and the other with the Mn(2+)-dependent activity, which are separable by their size difference. The 70-kDa adenylyl cyclase-associated protein (CAP) existed in the former complex but not in the latter. Missense mutations in conserved motifs of the leucine-rich repeats of the catalytic subunit of adenylyl cyclase abolished the RAS-dependent activity, which was accompanied by formation of a very high molecular weight complex having the Mn(2+)-dependent activity. Contrary to previous results, disruption of the gene encoding CAP did not alter the extent of RAS protein-dependent activation of adenylyl cyclase, while a concomitant decrease in the size of the RAS-responsive complex was observed. These results indicate that CAP is not essential for interaction of the yeast adenylyl cyclase with RAS proteins even though it is an inherent component of the RAS-responsive adenylyl cyclase complex. PMID- 1406673 TI - Cooperative binding of the Xenopus RNA polymerase I transcription factor xUBF to repetitive ribosomal gene enhancers. AB - Upstream binding factor (UBF) is a DNA-binding transcription factor implicated in ribosomal gene promoter and enhancer function in vertebrates. UBF is unusual in that it has multiple DNA-binding domains with homology to high-mobility-group (HMG) nonhistone chromosomal proteins 1 and 2. However, a recognizable DNA consensus sequence for UBF binding is lacking. In this study, we have used gel retardation and DNase I footprinting to examine Xenopus UBF (xUBF) binding to Xenopus laevis ribosomal gene enhancers. We show that UBF has a minimum requirement for about 60 bp of DNA, the size of the short enhancer variant in X. laevis. Stronger UBF binding occurs on the longer enhancer variant (81 bp) and on multiple enhancers linked head to tail. In vivo, Xenopus ribosomal gene enhancers exist in blocks of 10 alternating 60- and 81-bp repeats within the intergenic spacer. In vitro, UBF binds cooperatively to probes with 10 enhancers, with five intermediate complexes observed in titration experiments. This suggests that, on average, one UBF dimer binds every two enhancers. A single UBF dimer can produce a DNase I footprint ranging in size from approximately 30 to about 115 bp on enhancer probes of different lengths. This observation is consistent with the hypothesis that multiple DNA-binding domains or subdomains within UBF bind independently, forming more-stable interactions on longer probes. PMID- 1406672 TI - Functional interference between the ubiquitous and constitutive octamer transcription factor 1 (OTF-1) and the glucocorticoid receptor by direct protein protein interaction involving the homeo subdomain of OTF-1. AB - The ubiquitous and constitutive octamer transcription factor OTF-1 (Oct 1) is the target of positive regulation by the potent herpes simplex virus trans-activator VP16, which forms a complex with the homeodomain of OTF-1. Here we present evidence that the glucocorticoid receptor can negatively regulate OTF-1 function by a mechanism that is independent of DNA binding. In vivo-expressed glucocorticoid receptor inhibited in a hormone-dependent manner activation of a minimal promoter construct carrying a functional octamer site. Moreover, expression of the receptor in vivo resulted in hormone-dependent repression of OTF-1-dependent DNA-binding activity in nuclear extract. In vitro, the DNA binding activity of partially purified OTF-1 was repressed following incubation with purified glucocorticoid receptor. Cross-linking and immunoprecipitation experiments indicated that the functional interference may be due to a strong association between these two proteins in solution. Finally, preliminary evidence indicates that the homeo subdomain of OTF-1 that directs formation of a complex with VP16 may also be critical for interaction with the glucocorticoid receptor. Thus, OTF-1 is a target for both positive and negative regulation by protein protein interaction. Moreover, the functional interference between OTF-1 and the glucocorticoid receptor represents a novel regulatory mechanism in the cross coupling of signal transduction pathways of nuclear receptors and constitutive transcription factors. PMID- 1406674 TI - A transcriptionally active form of GAL4 is phosphorylated and associated with GAL80. AB - The GAL4 activator and GAL80 repressor proteins regulate the expression of yeast genes in response to galactose. A complex of the two proteins isolated from glucose-grown cells is inactive in an in vitro transcription reaction but binds DNA and blocks activation by the GAL4-VP16 chimeric activator. The complex purified from galactose-grown cells contains a mixture of phosphorylated and unphosphorylated forms of GAL4. The galactose-induced form of GAL4 activates in vitro transcription to levels similar to those seen with GAL4-VP16. The induced GAL4 complex is indistinguishable in size and apparent shape from the uninduced complex, consistent with a continued association with GAL80. These results confirm in vivo analyses that correlate GAL4 phosphorylation with galactose induction and support a model of transcriptional activation that does not require GAL80 dissociation. PMID- 1406675 TI - Effects of histone acetylation on chromatin topology in vivo. AB - Recently a model for eukaryotic transcriptional activation has been proposed in which histone hyperacetylation causes release of nucleosomal supercoils, and this unconstrained tension in turn stimulates transcription (V. G. Norton, B. S. Imai, P. Yau, and E. M. Bradbury, Cell 57:449-457, 1989; V. G. Norton, K. W. Marvin, P. Yau, and E. M. Bradbury, J. Biol. Chem. 265:19848-19852, 1990). These studies analyzed the effect of histone hyperacetylation on the change in topological linking number which occurs during nucleosome assembly in vitro. We have tested this model by determining the effect of histone hyperacetylation on the linking number change which occurs during assembly in vivo. We find that butyrate treatment of cells infected with simian virus 40 results in hyperacetylation of the histones of the extracted viral minichromosome as expected. However, the change in constrained supercoils of the minichromosome DNA is minimal, a result which is inconsistent with the proposed model. These results indicate that the proposed mechanism of transcriptional activation is unlikely to take place in the cell. PMID- 1406676 TI - Existence of different Fos/Jun complexes during the G0-to-G1 transition and during exponential growth in mouse fibroblasts: differential role of Fos proteins. AB - We have determined the different Fos/Jun complexes present in Swiss 3T3 cells either following serum stimulation of quiescent cells or during exponential growth by immunoprecipitation analyses. We have shown that while c-Fos is the major Fos protein associated with the Jun proteins (c-Jun, JunB, and JunD) soon after serum stimulation, at later times Fra-1 and Fra-2 are the predominant Fos proteins associated with the different Jun proteins. During exponential growth, the synthesis of Fra-1 and Fra-2 is maintained at a significant level, in contrast to c-Fos and FosB, which are expressed at very low or undetectable levels. Consequently, Fra-1 and Fra-2 are the main Fos proteins complexed with the Jun proteins in asynchronously growing cells. To determine whether the Fos proteins are differentially required during the G0-to-G1 transition and exponential growth for the entrance into S phase, we microinjected affinity purified antibodies directed against c-Fos, FosB, Fra-1, and Fra-2. We have found that while the activities of c-Fos and FosB are required mostly during the G0-to G1 transition, Fra-1 and Fra-2 are involved both in the G0-to-G1 transition and in asynchronous growth. PMID- 1406677 TI - A 40-kilodalton protein binds specifically to an upstream sequence element essential for muscle-specific transcription of the human myoglobin promoter. AB - To define transcriptional control elements responsible for muscle-specific expression of the human myoglobin gene, we performed mutational analysis of upstream sequences (nucleotide positions -373 to +7 relative to the transcriptional start site) linked to a firefly luciferase gene. Transient expression assays in avian and mammalian cells indicated that a CCCACCCCC (CCAC box) sequence (-223 to -204) is necessary for muscle-specific transcription directed either by the native myoglobin promoter or by a heterologous minimal promoter linked to the myoglobin upstream enhancer region. A putative MEF2-like site (-160 to -169) was likewise necessary for full transcriptional activity in myotubes. Mutations within either of two CANNTG (E-box) motifs (-176 to -148) had only minimal effects on promoter function. We identified and partially purified from nuclear extracts a 40-kDa protein (CBF40) that binds specifically to oligonucleotides containing the CCAC box sequence. A mutation of the CCAC box that disrupted promoter function in vivo also impaired binding of CBF40 in vitro. These data suggest that cooperative interactions between CBF40 and other factors including MEF-2 are required for expression of the human myoglobin gene in skeletal muscle. PMID- 1406678 TI - Identification of a human cDNA encoding a protein that is structurally and functionally related to the yeast adenylyl cyclase-associated CAP proteins. AB - The adenylyl cyclases of both Saccharomyces cerevisiae and Schizosaccharomyces pombe are associated with related proteins named CAP. In S. cerevisiae, CAP is required for cellular responses mediated by the RAS/cyclic AMP pathway. Both yeast CAPs appear to be bifunctional proteins: the N-terminal domains are required for the proper function of adenylyl cyclase, while loss of the C terminal domains results in morphological and nutritional defects that appear to be unrelated to the cAMP pathways. Expression of either yeast CAP in the heterologous yeast suppresses phenotypes associated with loss of the C-terminal domain of the endogenous CAP but does not suppress loss of the N-terminal domain. On the basis of the homology between the two yeast CAP proteins, we have designed degenerate oligonucleotides that we used to detect, by the polymerase chain reaction method, a human cDNA fragment encoding a CAP-related peptide. Using the polymerase chain reaction fragment as a probe, we isolated a human cDNA clone encoding a 475-amino-acid protein that is homologous to the yeast CAP proteins. Expression of the human CAP protein in S. cerevisiae suppresses the phenotypes associated with loss of the C-terminal domain of CAP but does not suppress phenotypes associated with loss of the N-terminal domain. Thus, CAP proteins have been structurally and, to some extent, functionally conserved in evolution between yeasts and mammals. PMID- 1406679 TI - Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino terminal transactivation domain of human p53. AB - Human DNA-PK is a nuclear, serine/threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding substrates, including the tumor suppressor protein p53. To identify which p53 residues are phosphorylated, we examined DNA-PK's ability to phosphorylate synthetic peptides corresponding to human p53 sequences. Serines 15 and 37 in the amino-terminal transactivation domain of human p53, and serines 7 and 18 of mouse p53, were phosphorylated by DNA-PK in the context of synthetic peptides. Other serines in these p53 peptides, and serines in other p53 peptides, including peptides containing the serine 315 p34cdc2 site and the serine 392 casein kinase II site, were not recognized by DNA PK or were phosphorylated less efficiently. Phosphorylation of the conserved serine 15 in human p53 peptides depended on the presence of an adjacent glutamine, and phosphorylation was inhibited by the presence of a nearby lysine. Phosphorylation of recombinant wild-type mouse p53 was inhibited at high DNA concentrations, suggesting that DNA-PK may phosphorylate p53 only when both are bound to DNA at nearby sites. Our study suggests that DNA-PK may have a role in regulating cell growth and indicates how phosphorylation of serine 15 in DNA bound p53 could alter p53 function. PMID- 1406680 TI - Functional asymmetry of the regions juxtaposed to the membrane-binding sequence of polyomavirus middle T antigen. AB - The functional importance of the two clusters of positively charged amino acids which flank the hydrophobic membrane-anchoring sequence of polyomavirus middle T (mT) protein has been investigated by using site-directed mutagenesis. A clear asymmetry was apparent. No effect on transformation was seen following multiple alterations or complete removal of the cluster at the carboxyl end of the protein. In contrast, a single substitution replacing the first arginine amino terminal to the hydrophobic stretch with glutamic acid, but not with lysine, histidine, or methionine, produced a partially transformation-defective mutant with a novel phenotype. This mutant failed to confer anchorage-independent growth on F111 established rat embryo fibroblasts but induced foci with altered morphology compared with wild-type mT. Biochemical studies on this mutant revealed that F111 clones expressing levels of mutant mT equivalent to those of wild-type controls showed a 65% reduction in pp60c-src activation and an 87% reduction in mT-associated phosphatidylinositol 3-kinase activity. However, F111 clones expressing seven times more mutant mT than did wild-type controls showed equal or greater levels of kinase activities yet remained incompletely transformed. Possible mechanisms involving this transformation-sensitive region of mT are discussed. PMID- 1406681 TI - Conformational activation of a basic helix-loop-helix protein (MyoD1) by the C terminal region of murine HSP90 (HSP84). AB - A murine cardiac lambda gt11 expression library was screened with an amphipathic helix antibody, and a recombinant representing the C-terminal 194 residues of murine HSP90 (HSP84) was cloned. Both recombinant and native HSP90s were then found to rapidly convert a basic helix-loop-helix protein (MyoD1) from an inactive to an active conformation, as assayed by sequence-specific DNA binding. The conversion process involves a transient interaction between HSP90 and MyoD1 and does not result in the formation of a stable tertiary complex. Conversion does not require ATP and occurs stoichiometrically in a dose-dependent fashion. HSP90 is an abundant, ubiquitous, and highly conserved protein present in most eukaryotic cells. These results provide direct evidence that HSP90 can affect the conformational structure of a DNA-binding protein. PMID- 1406682 TI - The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulinlike growth factor 1 with its receptor. AB - We have used a plasmid expressing a temperature-sensitive (ts) mutant of simian virus 40 (SV40) T antigen, stably transfected into 3T3 cells, to study the role of insulinlike growth factor 1 (IGF-1) and its receptor in T-antigen-mediated growth. While 3T3 cells do not grow in serum-free medium, in 1% serum, or with the sole addition of either platelet-derived growth factor (PDGF) or IGF-1, cells expressing the tsA T antigen (BALB 58 cells) grow at 34 degrees C in either PDGF or 1% serum but not in IGF-1. At the restrictive temperature (39.6 degrees C), these cells can only grow in 10% serum. We show that BALB 58 cells, at 34 degrees C, have a markedly increased expression of IGF-1 and IGF-1 mRNA and that their growth in 1% serum (at 34 degrees C) is inhibited by an antisense oligodeoxynucleotide to the IGF-1 receptor RNA. When this tsA plasmid is stably transfected into cells constitutively overexpressing the human IGF-1 receptor cDNA, the resulting cell lines show a constitutively phosphorylated IGF-1 receptor and grow in serum-free medium at 34 degrees C (but not at 39.6 degrees C). A functional SV40 T antigen also increases the expression of a plasmid in which the reporter luciferase gene is under the control of a rat IGF-1 promoter. We conclude (i) that the SV40 T antigen induces the expression of IGF-1 and IGF-1 mRNA, at least in part by a transcriptional mechanism, thus altering the growth factors requirements, and (ii) that, in BALB/c3t3 cells, the SV40 T antigen necessitates a functional IGF-1 receptor for its growth-stimulating effect in low serum (or PDGF). PMID- 1406683 TI - Raf-1 protein kinase is an integral component of the oncogenic signal cascade shared by epidermal growth factor and platelet-derived growth factor. AB - Our recent studies with cell mutants indicate that a cascade shared by the epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) signals exists in NRK cells and mediates oncogenic signals induced by many oncogenes (A. Masuda, S. Kizaka-Kondoh, H. Miwatani, Y. Terada, H. Nojima, and H. Okayama, New Biol. 4:489-503, 1992). We have employed the antisense RNA technique to investigate possible involvement of Raf-1 kinase in this signal transduction cascade. NRK cell clones highly reduced in the Raf-1 production are generated by the expression of a c-raf-1 antisense RNA. They have no apparent growth defects and retain proper mitotic responses to growth factors but are refractory to transformation by EGF or PDGF plus transforming growth factor beta, v-erbB, v fms, v-K-ras, v-mos, v-fos, v-src, simian virus 40 large T, and polyomavirus middle T but not by v-raf or adenovirus E1A. These results not only support our model for the oncogenic signal cascade but also lead to the conclusion that Raf-1 protein kinase is a downstream component of this oncogenic signal cascade shared by EGF and PDGF. PMID- 1406684 TI - Definition of the transcriptional activation domain of recombinant 43-kilodalton USF. AB - The cellular transcription factor USF is involved in the regulation of both cellular and viral genes and consists of 43- and 44-kDa polypeptides which independently show site-specific DNA binding. Cloning of the corresponding cDNA revealed that the 43-kDa polypeptide (USF43) is a member of the basic (B)-helix loop-helix (HLH)-leucine zipper (LZ) family of proteins and provided a means for its functional dissection. Initial structure-function studies revealed that the HLH and LZ regions are both important for USF43 oligomerization and DNA binding. The studies presented here have focused on the determination of domains that contribute to transcriptional activation in vitro and show that (i) both a small region close to the N terminus and a region between residues 93 and 156 contribute strongly to transcriptional activation, (ii) full activation depends on the presence of both domains, (iii) the B-HLH-LZ region has no intrinsic activation potential but DNA binding is absolutely required for transcriptional activation, and (iv) the B-HLH-LZ region can be replaced by the Gal4 DNA binding domain without loss of activation potential. PMID- 1406685 TI - A Drosophila rotund transcript expressed during spermatogenesis and imaginal disc morphogenesis encodes a protein which is similar to human Rac GTPase-activating (racGAP) proteins. AB - The rotund (rn) locus of Drosophila melanogaster at cytogenetic position 84D3,4 has been isolated and cloned on the basis of the mutant phenotype: an absence of structures in the subdistal regions of the appendages. The shortened appendages are the consequence of a localized cell death in the imaginal discs, precursors of the adult appendages. Physical characterization of the rn locus has demonstrated that it is relatively large, occupying a minimum of 50 kb. There are two major transcripts of 1.7 kb (m1.7) and 5.3 kb (m5.3). We present here the sequence analysis of m1.7 and its putative product, rnprot1.7, and show that rnprot1.7 is similar to the product of the human n-chimaerin gene, which is expressed in brain and testes. Recently, the GAP activity of n-chimaerin was demonstrated and shown to be specific for the Rac subfamily of the Ras oncoproteins. The Rac proteins have been implicated in the regulation of secretory processes. In addition to being expressed in the imaginal discs, the m1.7 racGAP transcript was detected in developmentally specific germ line cells of the testes, the primary spermatocytes. PMID- 1406686 TI - p53 is covalently linked to 5.8S rRNA. AB - We report here the isolation and identification of the RNA specifically immunoprecipitated and covalently linked to the tumor suppressor gene product p53. After treatment with proteinase K, the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) band of p53 yields a single, discrete 157 nucleotide RNA, which was cloned, sequenced, and identified as 5.8S rRNA. 5.8S rRNA was obtained only after proteolysis of the p53 SDS-PAGE band. Free 5.8S rRNA did not comigrate with p53 in SDS-PAGE. This RNA was only immunoprecipitated from cells containing p53. Protein-free RNA obtained by proteolysis of the p53 band hybridized to the single-stranded DNA vector containing the antisense sequence of 5.8S rRNA. The covalence of the p53-5.8S rRNA linkage was demonstrated by the following findings: (i) p53 and the linked 5.8S rRNA comigrated in SDS-PAGE; (ii) only after treatment of the p53-RNA complex with proteinase K did the 5.8S rRNA migrate differently from p53-linked 5.8S rRNA; and (iii) this isolated RNA was found linked to phosphoserine, presumably at the 5' end. Covalent linkage to the single, specific RNA suggests that p53 may be involved in regulating the expression or function of 5.8S rRNA. PMID- 1406687 TI - Tumorigenicity of the met proto-oncogene and the gene for hepatocyte growth factor. AB - The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). It was previously shown that, like the oncogenic tpr-met, the mouse met proto-oncogene transforms NIH 3T3 cells. We have established NIH 3T3 cells stably expressing both human (Methu) and mouse (Metmu) met proto-oncogene products. The protein products are properly processed and appear on the cell surface. NIH 3T3 cells express endogenous mouse HGF/SF mRNA, suggesting an autocrine activation mechanism for transformation by Metmu. However, the tumor-forming activity of Methu in NIH 3T3 cells is very low compared with that of Metmu, but efficient tumorigenesis occurs when Methu and HGF/SFhu are coexpressed. These results are consistent with an autocrine transformation mechanism and suggest further that the endogenous murine factor inefficiently activates the tumorigenic potential of Methu. The tumorigenicity observed with reciprocal chimeric human and mouse receptors that exchange external ligand-binding domains supports this conclusion. We also show that HGF/SFhu expressed in NIH 3T3 cells produces tumors in nude mice. PMID- 1406688 TI - C-terminal truncation of RAP1 results in the deregulation of telomere size, stability, and function in Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae DNA-binding protein RAP1 is capable of binding in vitro to sequences from a wide variety of genomic loci, including upstream activating sequence elements, the HML and HMR silencer regions, and the poly(G1 3T) tracts of telomeres. Recent biochemical and genetic studies have suggested that RAP1 physically and functionally interacts with the yeast telomere. To further investigate the role of RAP1 at the telomere, we have identified and characterized three intragenic suppressors of a temperature-sensitive allele of RAP1, rap1-5. These telomere deficiency (rap1t) alleles confer several novel phenotypes. First, telomere tract size elongates to up to 4 kb greater than sizes of wild-type or rap1-5 telomeres. Second, telomeres are highly unstable and are subject to rapid, but reversible, deletion of part or all of the increase in telomeric tract length. Telomeric deletion does not require the RAD52 or RAD1 gene product. Third, chromosome loss and nondisjunction rates are elevated 15- to 30-fold above wild-type levels. Sequencing analysis has shown that each rap1t allele contains a nonsense mutation within a discrete region between amino acids 663 and 684. Mobility shift and Western immunoblot analyses indicate that each allele produces a truncated RAP1 protein, lacking the C-terminal 144 to 165 amino acids but capable of efficient DNA binding. These data suggest that RAP1 is a central regulator of both telomere and chromosome stability and define a C terminal domain that, while dispensable for viability, is required for these telomeric functions. PMID- 1406689 TI - Temporal order of DNA replication in the H-2 major histocompatibility complex of the mouse. AB - As an approach to mapping replicons in an extended chromosomal region, the temporal order of DNA replication was analyzed in the murine major histocompatibility gene complex (MHC). Replicating DNA from T-lymphoma and myelomonocyte cell lines was density labeled with bromodeoxyuridine and extracted from cells which had been fractionated into different stages of S phase by centrifugal elutriation. The replicating DNA from each fraction of S phase was separated from nonreplicating DNA on density gradients, blotted, and hybridized with 34 specific MHC probes. The earliest replication occurred in the vicinity of transcribed genes K, HAM1 and HAM2, RD, B144, D, L, T18, and T3. The temporal order of replication of groups of DNA segments suggests the location of five or six replicons within the H-2 complex, some of which appear to be either unidirectional or markedly asymmetric. The rates of replication through each of these apparent replicons appear to be similar. The TL region of the S49.1 T lymphoma cells, which contains at least three transcribed genes, replicates earlier than the inactive TL region of WEHI-3 myelomonocytic cells. These results provide further evidence of a relationship between transcription and the initiation of DNA replication in mammalian cells. The mouse MHC examined in this study is the largest chromosomal region (> 2,000 kb) measured for timing of replication to date. PMID- 1406690 TI - TFIIA induces conformational changes in TFIID via interactions with the basic repeat. AB - DNA-binding studies with Saccharomyces cerevisiae TFIID point mutants indicated that TFIIA interacts with the basic repeat region of TFIID and induces structural changes. The latter was shown by the ability of TFIIA to compensate for TFIID point mutants defective for DNA binding. Interaction with TFIIA also rendered TFIID binding temperature independent, thus mimicking the effect of removing the nonconserved N terminus of TFIID. In addition, N-terminal truncation of the TFIID point mutants defective for DNA binding mimicked the ability of TFIIA to restore DNA binding of those mutants. Taken together, these results suggest that TFIIA enhances TFIID binding to DNA by eliminating an otherwise inhibitory effect of the nonconserved N terminus of TFIID. Furthermore, analyses of TFIID contact points on DNA and binding studies with TATA-containing oligonucleotide probes showed that TFIIA decreases the effect of sequences flanking the adenovirus major late TATA element on TFIID binding to DNA, suggesting a possible role of TFIIA in allowing TFIID to recognize a wider variety of promoters. PMID- 1406691 TI - Synthetic lethal mutations suggest interactions between U5 small nuclear RNA and four proteins required for the second step of splicing. AB - To investigate the function of the U5 small nuclear ribonucleoprotein (snRNP) in pre-mRNA splicing, we have screened for factors that genetically interact with Saccharomyces cerevisiae U5 snRNA. We isolated trans-acting mutations that exacerbate the phenotypes of conditional alleles of the U5 snRNA and named these genes SLU, for synergistically lethal with U5 snRNA. SLU1 and SLU2 are essential for the first catalytic step of splicing, while SLU7 and SLU4 (an allele of PRP17 [U. Vijayraghavan, M. Company, and J. Abelson, Genes Dev. 3:1206-1216, 1989]) are required only for the second step of splicing. Furthermore, slu4-1 and slu7-1 are lethal in combination with mutations in PRP16 and PRP18, which also function in the second step, but not with mutations in factors required for the first catalytic step, such as PRP8 and PRP4. We infer from these data that SLU4, SLU7, PRP18, PRP16, and the U5 snRNA interact functionally and that a major role of the U5 snRNP is to coordinate a set of factors that are required for the completion of the second catalytic step of splicing. PMID- 1406692 TI - Characterization of the human immunoglobulin kappa gene 3' enhancer: functional importance of three motifs that demonstrate B-cell-specific in vivo footprints. AB - Using a combination of in vivo footprinting and site-directed mutagenesis, we have functionally characterized an enhancer located 12 kb downstream of the human immunoglobulin kappa constant-region gene. The core enhancer region is highly homologous to the murine 3' kappa enhancer. However, in addition to two regulatory elements homologous to the functional motifs of the murine enhancer, we find a third positive regulatory element in the human enhancer. This element is associated with an 11/12-bp direct repeat (DR) that is well conserved in the murine locus but was not recognized as functionally important in the murine enhancer. Mutation of any of the three motifs of the human enhancer decreases its activity to 3 to 20% of the wild-type level, indicating cooperative interaction between these elements. The DR motif does not resemble any known enhancer element and does not appear to function as a transcriptional activator on its own when present in multiple copies. Interestingly, nuclear extracts from both B- and T cell lines contain factors binding to DR in vitro, but in vivo footprinting shows no evidence of protein-DNA binding in the T-cell line. This finding suggests that an additional regulatory mechanism, such as the effect of chromatin configuration on accessibility, may be involved in the B-cell-restricted activity of the human 3' kappa enhancer. PMID- 1406693 TI - Purified cofactors and histone H1 mediate transcriptional regulation by CTF/NF-I. AB - The initiation of RNA polymerase II transcription is controlled by DNA sequence specific activator proteins, in combination with cofactor polypeptides whose function is poorly understood. Transcriptional cofactors of the CTF-1 activator were purified on the basis of their affinity for the regulatory protein. These purified cofactors were found to be required for CTF-1-regulated transcription, and they counteracted squelching by an excess of activator in in vitro reconstitution experiments. Interestingly, the cofactors possessed an inhibitory activity for basal transcription, which was relieved by the further addition of the activator. Histone H1 also contributes to the regulation of transcription by CTF-1, whereby the activator prevents repression of the basal transcription machinery by the histone. However, histone H1 could not replace the cofactors for CTF-1-regulated transcription, indicating that they possess distinct transcriptional properties. Furthermore, the purified cofactors were found to be required, together with the activator, in order to antagonize the histone mediated repression of transcription. These results suggest that CTF-1 and its cofactors function by regulating the assembly of the basal transcription machinery onto the promoter when the latter is in competition with DNA-binding inhibitory proteins such as histone H1. PMID- 1406694 TI - Identification of a new set of cell cycle-regulatory genes that regulate S-phase transcription of histone genes in Saccharomyces cerevisiae. AB - Histone mRNA synthesis is tightly regulated to S phase of the yeast Saccharomyces cerevisiae cell cycle as a result of transcriptional and posttranscriptional controls. Moreover, histone gene transcription decreases rapidly if DNA replication is inhibited by hydroxyurea or if cells are arrested in G1 by the mating pheromone alpha-factor. To identify the transcriptional controls responsible for cycle-specific histone mRNA synthesis, we have developed a selection for mutations which disrupt this process. Using this approach, we have isolated five mutants (hpc1, hpc2, hpc3, hpc4, and hpc5) in which cell cycle regulation of histone gene transcription is altered. All of these mutations are recessive and belong to separate complementation groups. Of these, only one (hpc1) falls in one of the three complementation groups identified previously by other means (M. A. Osley and D. Lycan, Mol. Cell. Biol. 7:4204-4210, 1987), indicating that at least seven different genes are involved in the cell cycle specific regulation of histone gene transcription. hpc4 is unique in that derepression occurs only in the presence of hydroxyurea but not alpha-factor, suggesting that at least one of the regulatory factors is specific to histone gene transcription after DNA replication is blocked. One of the hpc mutations (hpc2) suppresses delta insertion mutations in the HIS4 and LYS2 loci. This effect allowed the cloning and sequence analysis of HPC2, which encodes a 67.5 kDa, highly charged basic protein. PMID- 1406695 TI - A Raf-1-related p110 polypeptide associates with the CD4-p56lck complex in T cells. AB - The CD4 and CD8 antigens on T cells have been shown to associate with the Src family member p56lck and a GTP-binding protein, p32. The identification of receptor interactions with intracellular mediators is essential in the elucidation of downstream signals mediated by engagement of these receptor complexes. In this study, we report the detection of an additional 110-kDa polypeptide (p110) associated with the CD4-p56lck complex in human peripheral blood T lymphocytes and leukemic T-cell lines. p110 bound preferentially to CD4 p56lck as an assembled complex and poorly, if at all, to the individual components. p110 was recognized directly by an antiserum to the C-terminal region of the serine/threonine kinase Raf-1 and is related to a p110 polypeptide detected in anti-Raf-1 immunoprecipitates. Despite its association with the CD4 p56lck complex, p110 was found to be phosphorylated predominantly on serine residues. Furthermore, phorbol ester treatment of cells resulted in a transient increase in the detection of p110 associated with CD4-p56lck, concomitant with the modulation of CD4-p56lck from the cell surface. This Raf-1-related p110 is therefore likely to play a role in signals generated from the CD4-p56lck complex. p110 may serve as a bridge between the CD4-p56lck complex and the serine/threonine kinase pathways of T-cell activation. PMID- 1406697 TI - 3,5,3'-Triiodothyronine positively regulates both MyoD1 gene transcription and terminal differentiation in C2 myoblasts. AB - Thyroid hormones are among the positive regulators of muscle development in vivo, but little is known about the way they work. We demonstrate here that MyoD1, one of the master genes controlling myogenesis, is a target of T3. After proliferating C2 myoblasts have been treated with T3 for 15 h, we observed a rise in MyoD1 expression at both the mRNA and protein levels. This is the first positive hormonal control of MyoD1 gene expression reported so far. We also provide data which suggest that T3 nuclear receptor(s) have a direct role on MyoD1 gene transcription: 1) C2 cells express the alpha 1 form of T3 nuclear receptors; 2) T3 up-regulates MyoD1 gene transcription and does not affect MyoD1 mRNA stability, as demonstrated by run-on and actinomycin D chase experiments, respectively; and 3) this transcriptional activation does not need the synthesis of intermediate protein(s) since it is not abolished by simultaneous treatment with cycloheximide. Moreover, in presence of T3, the increase of MyoD1 transcripts is associated with a faster terminal differentiation. Indeed we observed an earlier expression of various markers of myogenesis including myogenin (a regulatory gene of the MyoD1 family mainly involved in the triggering of terminal differentiation), myosin light chain 1A, and troponin T in T3-treated cells vs. untreated cells. We suggest that the regulation of a pivotal myogenic gene could be an important step in the control exerted by T3 on muscle development in vivo. PMID- 1406698 TI - Nucleotide sequence and tissue distribution of three insulin-like growth factor I prohormones in salmon. AB - Tissue distribution and potential alternative splicing of insulin-like growth factor I (IGF-I) messenger RNA were studied using reverse transcriptase polymerase chain reaction (RT-PCR) on RNA from several tissues at various stages of the life cycle of coho salmon (Oncorhynchus kisutch). DNA sequence analysis of RT-PCR products revealed three IGF-I mRNA transcripts, designated Ea-1, Ea-2, and Ea-3, which code for three distinct prohormones, IGF-IA-1, IGF-IA-2, and IGF-IA 3, respectively. The E-domain of proIGF-IA-1 is 35 amino acids long and shares 77% sequence identity with the E-domain of human proIGF-IA, which is also 35 amino acids long. The proIGF-IA-2 and proIGF-IA-3 E-domains are homologous to the proIGF-IA-1 E-domain but contain 27 and 39 amino acid inserts, respectively, between Lys86 and Glu87. In the human IGF-I gene Lys86 is coded by exon 4 and Glu87 is coded by exon 6. This suggests that Ea-2 and Ea-3 transcripts may be the result of alternative splicing during pre-mRNA processing. All three transcripts were readily detectable using a solution hybridization/RNase protection assay. Furthermore, RT-PCR and DNA sequencing analysis indicate the presence of three IGF-I prohormones in another member of the Salmonidae family, the Atlantic salmon (Salmo salar). An analysis of IGF-I and -II E-domains from several vertebrates suggests that certain chemical and physical properties of the molecule are well conserved despite wide variations in primary structure. Ea-1, Ea-2, and Ea-3 transcripts were found in whole embryos, and liver, muscle, and brain of juvenile and adult salmon. At least one IGF-I transcript was found in heart, kidney, testes, ovary, adipose tissue, and spleen of juvenile salmon. These results indicate that IGF-I is expressed during embryonic development of fish, and that most tissues are capable of IGF-I mRNA production. These data also indicate that pre-mRNA transcripts can be alternatively spliced to yield at least three prohormones. PMID- 1406696 TI - Expression of chimeric genes by the light-regulated cabII-1 promoter in Chlamydomonas reinhardtii: a cabII-1/nit1 gene functions as a dominant selectable marker in a nit1- nit2- strain. AB - In Chlamydomonas reinhardtii, expression of the cabII-1 gene increases dramatically in response to light (cabII-1 encodes one of the light-harvesting chlorophyll a/b-binding proteins of photosystem II). We have used a region upstream of the cabII-1 gene in translational fusions to the bacterial uidA gene (encodes beta-glucuronidase) and transcriptional fusions to the Chlamydomonas nitrate reductase gene (nit1). Chlamydomonas transformants carrying intact copies of the chimeric uidA gene do not express beta-glucuronidase at the level of enzyme activity or mRNA accumulation. Methylation in the cabII-1 promoter region of the introduced gene is extensive in these strains, suggesting that newly introduced foreign genes may be recognized and silenced by a cellular mechanism that is correlated with increased methylation. Transformants that express the chimeric cabII-1/nit1 gene have been recovered. In contrast to the endogenous nit1 gene, the chimeric cabII-1/nit1 gene is expressed in ammonium-containing medium. Moreover, nit1 mRNA accumulation is dramatically stimulated by light, with a time course that is indistinguishable from that of the endogenous cabII-1 gene. The cabII-1/nit1 gene has been used to select transformants in a nit1- nit2 Chlamydomonas strain (CC400G) and should be useful for transformation of the large number of mutants in the Ebersold-Levine lineage, which carry the same mutations. PMID- 1406699 TI - Pro-453 to Ser mutation in CYP21 is associated with nonclassic steroid 21 hydroxylase deficiency. AB - Steroid 21-hydroxylase deficiency is the leading cause of impaired cortisol synthesis in congenital adrenal hyperplasia (CAH), with the nonclassic form (NC) comprising approximately 1% of the Caucasian population. The structure of the CYP21 gene was studied in 13 unrelated NC-CAH patients, three affected siblings, and 55 blood donors using polymerase chain reaction. In addition to the Leu-281 and Leu-30 mutations previously associated with NC-CAH, the finding of a Pro-453 to Ser mutation in exon-10 of CYP21 in the NC-CAH patients is reported. Ser-453 was found in 46.2% of unrelated NC-CAH patients, but only 7.7% and 3.6% of salt wasting CAH patients and blood donors, respectively. In contrast to the Leu-281 and Leu-30 mutations, Ser-453 has not been previously detected in the CYP21 pseudogene (CYP21P) and, therefore, has not likely arisen by gene conversion. PMID- 1406700 TI - Molecular cloning and expression of a full-length complementary DNA encoding the guinea pig adrenocortical estrogen sulfotransferase. AB - Complementary DNA for the guinea pig adrenocortical estrogen sulfotransferase (EST) has been cloned and expressed. Oligonucleotides, based on amino acid sequences of the purified 34-kilodalton protein, were synthesized and used to generate a specific probe by polymerase chain reaction for screening a guinea pig adrenal cDNA library. The polymerase chain reaction rapid amplification of cDNA ends procedure was employed to obtain the 3' and 5' cDNA ends, and a full-length cDNA was constructed. The cloned cDNA consists of 1192 base pairs and encodes a protein of 296 amino acids with a calculated molecular mass of 35,161 daltons. A computer search of the protein data banks revealed significant homology with several sulfotransferases: 71% with bovine placental estrogen sulfotransferase, 52% with rat liver phenol sulfotransferase, 35% with rat liver hydroxysteroid sulfotransferase, and 36% with rat liver senescence marker protein 2. The EST cDNA was inserted into the pcDNA I eukaryotic expression vector and transfected into COS-7 cells. The successful expression of EST cDNA in COS-7 cells was ascertained by Western blot analysis using antibody generated against the protein used to obtain the original amino acid sequence. Additionally, the expressed protein was clearly functional. Only after transfection with EST cDNA was there detectable estradiol sulfotransferase activity in COS-7 cell cytosol. The expressed EST had a single pI of 6.4, whereas native guinea pig adrenocortical EST exhibits four primary charge isoforms. The majority of adrenocortical EST activity focuses as a broad bimodal band in the pH range of 6.6-6.2; additionally, three other discrete immunocross-reactive isoforms are present with pIs of 5.5, 5.4, and 5.2. Antibodies generated against each individual isoform cross-react with all the other isoforms and with the expressed protein. These isoforms were previously reported to be isomers of a pregnenolone-binding protein; however it is now evident that the isoforms and antibodies raised against them are EST specific. Under high stringency hybridization conditions, EST mRNA was only detected in the adrenal gland, where two mRNA species of 1.4 and 1.8 kilobases were evident; when low stringency conditions were used, a faint 1.4-kilobase band was also detected in the liver. Primer extension analysis revealed that the multiple mRNAs do not arise from differential transcription initiation sites, and genomic Southern blot analysis indicated that the multiple mRNAs arise from a single gene. PMID- 1406701 TI - Activation of insulin-like growth factor II expression during skeletal muscle regeneration in the rat: correlation with myotube formation. AB - Insulin-like growth factors (IGFs) are important stimulators of proliferation and differentiation of cultured myoblasts. It has previously been shown that IGF-I is induced during muscle regeneration in rodents, however, little is known about the expression of IGF-II. Therefore, two in vivo models were used to analyze IGF-II mRNA expression during skeletal muscle regeneration in the rat: injection of the snake venom notexin and induction of ischemia. During the regeneration process the levels of both IGF-I and IGF-II mRNA were transiently induced, as analyzed by solution hybridization. Both IGF-I-like immunoreactivity and IGF-II-like immunoreactivity were found to be present during muscle regeneration. In a time course study, induction of IGF-II was preceded by IGF-I, both at the mRNA and protein levels. Using alpha- and beta-actin as markers for different stages of skeletal muscle differentiation, together with the immunohistochemistry data, it is concluded that the expression of IGF-I and IGF-II occurs at different differentiation stages, and that IGF-II appears concomitant to the formation of myotubes. These results suggest that each IGF has a distinct role during the differentiation of muscle cells. PMID- 1406702 TI - The Nb2 form of prolactin receptor is able to activate a milk protein gene promoter. AB - We have recently cloned a cDNA encoding a mutant form of PRL receptor (PRL-R) from Nb2 cells, a PRL-dependent T lymphocyte-derived cell line. This cDNA is identical to the long form of the rat PRL-R, except for a deletion of 594 base pairs in the cytoplasmic domain, resulting in a mature receptor protein of 393 amino acids. Although a segment containing three cytoplasmic regions of moderate to high amino acid sequence identity with members of the PRL/GH receptor family is missing in this receptor form, the region of highest (70%) identity is retained. In the following studies, a homologous functional assay was developed to test the activity of three forms of receptor with respect to their ability to transmit a lactogenic signal. In this system, CHO cells were transiently transfected with a construct containing 2300 base pairs of the 5'-flanking sequence of the rat beta-casein gene fused to the chloramphenicol acetyltransferase (CAT) gene and an expression vector containing the various forms of rat PRL-R cDNA. The transfected cells were grown in serum-free medium in the absence or presence of PRL. In cells transfected with the long form of the PRL-R and beta-casein/CAT construct, a 7.2- +/- 0.9-fold induction (n = 3) of CAT activity was seen when cells were cultured in the presence of 400 ng/ml PRL and 1 micrograms/ml hydrocortisone. This level of stimulation was similar to that observed for the ovine beta-lactoglobulin/CAT construct in which a 5.7- +/- 1.2 fold (n = 3) effect was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1406703 TI - Steroidogenic factor I, a key regulator of steroidogenic enzyme expression, is the mouse homolog of fushi tarazu-factor I. AB - We proposed that a cell-selective regulatory protein coordinately regulates the expression of three enzymes that are required for the biosynthesis of corticosteroids: cholesterol side chain cleavage enzyme, steroid 21-hydroxylase, and the aldosterone synthase isozyme of steroid 11 beta-hydroxylase. In this report, we identify a 53-kilodalton protein, termed steroidogenic factor 1 (SF 1), that interacts with the related promoter elements from these steroidogenic enzymes, and we isolate and characterize a cDNA that very likely encodes this protein. We first showed that nuclear extracts from bovine adrenal glands interact with the mouse steroidogenic regulatory elements, forming complexes indistinguishable from those produced by nuclear extracts from mouse Y1 adrenocortical cells. These bovine adrenal extracts were subjected to sequential ion exchange and affinity chromatography to yield a highly enriched preparation of SF-1. The predominant protein in the affinity-purified preparation comigrated with shift activity and had a mol wt of 53,000; UV cross-linking experiments demonstrated directly that this 53-kilodalton protein interacted with the steroidogenic regulatory element. Even with this marked enrichment, affinity purified SF-1 bound six steroidogenic regulatory elements. These results support strongly the model that a steroidogenic cell-selective protein interacts with related promoter elements from three steroidogenic enzymes to regulate their coordinate expression. The recognition sequence of SF-1 closely resembles those of nuclear hormone receptor family members, suggesting that SF-1 may belong to this supergene family. By screening a Y1 cell cDNA library with the DNA-binding region of the H-2RIIBP nuclear hormone receptor cDNA, we isolated a cDNA that is selectively expressed in steroidogenic cells. When expressed as a glutathione S transferase fusion protein in Escherichia. coli, the protein encoded by this cDNA interacts with all six related steroidogenic regulatory elements with a binding specificity indistinguishable from that of SF-1. Surprisingly, the sequence of the putative DNA-binding domain of this cDNA matches exactly the corresponding sequence of the mouse homolog of the Drosophila transcription factor fushi tarazu factor I. The demonstration that a member of the nuclear hormone receptor family interacts with the steroidogenic regulatory elements provides intriguing insights into possible mechanisms by which these essential genes are regulated. PMID- 1406704 TI - Effects of calcium and calcium ionophores on prolactin gene expression in GH3 and 235-1 rat pituitary tumor cells. AB - Previous observations that extracellular calcium (Ca2+) enhanced PRL mRNA levels posttranscriptionally in GH3 rat pituitary tumor cells were made using double stranded transcription probes. The effects of Ca2+ and the Ca2+ ionophore, ionomycin, on PRL gene expression in GH3 and 235-1 cells were investigated using site- and strand-specific probes. Treatment of GH3 and 235-1 cells with 0.5 mM Ca2+ in serum-free medium specifically increased PRL mRNA levels by severalfold. In 235-1 but not GH3 cells PRL gene transcription was comparably induced by Ca2+. Use of single-stranded 5' and 3' probes revealed no antisense transcription, nor any Ca2+ effect on transcriptional elongation. Treatment with Ca2+ plus ionomycin inhibited PRL mRNA levels and gene transcription in both cell lines. Although their PRL gene transcription rates are similar, several basic differences were noted between the cell lines. The 235-1 cells exhibit a different profile of nuclear PRL pre-RNAs than GH3 cells. Also, mRNA levels for a Ca(2+)-regulated gene (GRP78) did not change in Ca(2+)-treated GH3 cells but decreased in Ca(2+) treated 235-1 cells. Ionomycin treatment increased GRP78 mRNA levels in both cell lines. Thus, addition of extracellular Ca2+ appears to affect [Ca2+]i in 235-1 but not GH3 cells, while ionomycin affects [Ca2+]i in both cell lines. These data suggest that changing [Ca2+]i modulates PRL gene transcription. The comparative data suggest that posttranscriptional PRL regulation is Ca(2+)-regulated in GH3 cells, but is constitutive in 235-1 cells. PMID- 1406705 TI - Posttranscriptional regulation of prolactin (PRL) gene expression in PRL deficient pituitary tumor cells. AB - Rat pituitary acidophils consist of somatotropes (GH+/PRL-), lactotropes (GH /PRL+), and lactosomatotropes (GH+/PRL+). Studies have indicated interconversion of these cell types in response to changing hormonal status. Representative tumor cell lines have been obtained for each acidophil cell type, and some display spontaneous interconversions. We examined whether the switch from GH3 cells (GH+/PRL+) to GH3LP and GC cells (both GH+/PRL-) involves repression of PRL gene expression at a transcriptional vs. posttranscriptional level. PRL mRNA is undetectable or barely detectable in GH3LP and GC cells. In contrast, nuclear extracts from these cells transcribe the PRL promoter in vitro, and their Pit-1 mRNA levels are comparable to those in GH3 cells. Nuclear run-on transcription assays demonstrated that the PRL gene is transcribed in GH3LP and GC cells at a rate of about 60% of that observed in GH3 cells. No evidence was obtained for a block to transcriptional elongation or for transcription in the antisense direction across the PRL gene. Northern blot analysis of nuclear RNA revealed partially degraded and undetectable PRL gene transcripts in GH3LP cells and GC cells, respectively. These findings indicate that PRL gene transcripts are specifically degraded in tumor cells which display a pure somatotrope phenotype and raise the possibility that the trans-differentiation of lactosomatotropes to somatotropes involves posttranscriptional regulation of PRL gene expression. PMID- 1406706 TI - Identification and characterization of the chicken transforming growth factor beta 3 promoter. AB - The promoter regions of the three mammalian transforming growth factor-beta genes (TGF-beta s 1, 2, and 3) have been recently cloned and characterized. The sequences show little similarity, suggesting different mechanisms of transcriptional control of these genes. To study differences in transcriptional regulation of mammalian and avian TGF-beta, we have cloned and sequenced the 5' flanking region of chicken TGF-beta 3. Characterization of this region showed a TATA box and cAMP-responsive element (CRE) and AP-2 binding site consensus sequences starting at 12 and 28 base pairs, respectively, upstream from the TATA box. Moreover, four additional AP-2-like sites, 10 binding sites for the transcription factor Sp1, as well as two AP-1-like sites were also identified. Except for 32 base pairs of identity centered around the TATA box and CRE site and four other relatively small regions of identity, the chicken TGF-beta 3 promoter was found to be structurally very different from the human TGF-beta 3 promoter. Promoter fragments were cloned into a chloramphenicol acetyltransferase reporter plasmid to study functional activity. Basal transcriptional activity of the promoter was regulated in quail fibrosarcoma QM7 cells and in human adenocarcinoma A375 cells by multiple upstream elements including the TATA, CRE, and AP-2 sites. As in the human TGF-beta 3 promoter, the CRE site showed activation by forskolin, an effect which could be shown by expression of TGF-beta 3 mRNA in cultured chicken and quail cells as well. Our results indicate a complex pattern of transcriptional regulation of the chicken TGF-beta 3 gene and suggest that differences in the regulation of expression of the genes for mammalian and avian TGF-beta 3 may result in part from the unique structure of their 5'-flanking regions. PMID- 1406707 TI - Homodimer formation is rate-limiting for high affinity DNA binding by glucocorticoid receptor. AB - The glucocorticoid receptor (GR) is a hormone-inducible transcription factor which activates transcription of specific genes by binding to a DNA sequence present in the promoters of inducible genes. These glucocorticoid response elements (GREs) have a conserved palindromic sequence. Each half-GRE palindrome binds one subunit of GR. We have assessed the relative affinity of GR monomers and homodimers for GRE and determined whether homodimer formation is rate limiting for high affinity GRE binding. The in vitro affinity of GRE binding by GR homodimers was approximately 2 x 10(-10) M, whereas it was approximately 1 nM for GR monomers. While homodimer:GRE complexes were very stable, monomer:GRE complexes appeared less stable in vitro. At low receptor concentration, GR preferentially bound GRE as a homodimer. Prior dilution of GR (equilibrium shifted to monomers) before addition to a GRE binding reaction resulted in slower kinetics of binding by comparison to parallel reactions in which concentrated (largely homodimeric) GR was added first. Taken together, these experiments suggest that homodimer formation is rate-limiting for high affinity GRE binding. A GRE mutant which contained only a half-binding site and which was unable to bind GR homodimers was also unable to confer glucocorticoid-inducible transcription. Taken together with previous work, these experiments support the model that GR homodimers are required for hormone-dependent activation of transcription and that receptor homodimer formation is rate-limiting for GRE binding. PMID- 1406708 TI - Insulin and insulin-like growth factor I regulate a thyroid-specific nuclear protein that binds to the thyroglobulin promoter. AB - The mechanism responsible for the stimulation of thyroglobulin (Tg) gene expression by insulin and insulin-like growth factor I (IGF-I) in rat thyroid FRTL-5 cells has been investigated. Both insulin and IGF-I stimulate transcription from the Tg promoter in a transient transfection assay demonstrating that the promoter used contains the DNA signals necessary for insulin and IGF-I regulation. Promoter mutations that interfere with the binding of thyroid transcription factor 1 (TTF-1), TTF-2, and the ubiquitous transcription factor abolish the insulin/IGF-I response, indicating that the three factors may be involved in the observed transcriptional control. Protein DNA binding studies did not reveal any effect of insulin/IGF-I on the ubiquitous transcription factor and the TTF-1 binding capacity. Instead, TTF-2 is absent in nuclear extracts from cells depleted of serum and insulin. Addition of insulin or IGF-I restores the TTF-2 concentration to normal levels and requires ongoing protein synthesis. The insulin effect was maximal at 24 h and at a concentration of 1 microgram/ml. The same effect was observed with a 10-fold lower concentration of IGF-I. These results suggest that insulin (probably through the IGF-I receptor) and IGF-I modulate the levels of TTF-2, which results in an increased expression of the Tg gene. PMID- 1406709 TI - R339H and P453S: CYP21 mutations associated with nonclassic steroid 21 hydroxylase deficiency that are not apparent gene conversions. AB - Steroid 21-hydroxylase deficiency is the most common enzymatic defect causing congenital adrenal hyperplasia, an inherited disorder of cortisol biosynthesis. All mutations thus far characterized that cause this disorder appear to result from recombinations between the gene encoding the enzyme, CYP21B (CYP21), and the adjacent pseudogene, CYP21A (CYP21P). These are either deletions caused by unequal crossing-over during meiosis or apparent transfers of deleterious sequences from CYP21A to CYP21B, a phenomenon termed gene conversion. However, a small percentage of alleles do not carry such a mutation. We analyzed DNA from a patient with the mild, nonclassic form of 21-hydroxylase deficiency, who carried one allele that had no gene conversions detectable by hybridization with oligonucleotide probes. Sequence analysis revealed that this allele carried two missense mutations, R339H and P453S, neither of which has been previously observed in CYP21A or CYP21B. Each of these mutations was introduced into CYP21 cDNA which was then expressed in COS1 cells using a vaccinia virus system. Each mutation reduced the ability of the enzyme to 21-hydroxylate 17 hydroxyprogesterone to 50% of normal and the ability to metabolize progesterone to 20% of normal. Thus, each of these mutations represents a potential nonclassic 21-hydroxylase deficiency allele that is not the result of an apparent gene conversion. PMID- 1406710 TI - Differential expression of neural cell adhesion molecule and cadherins in pancreatic islets, glucagonomas, and insulinomas. AB - The endocrine cells of the pancreas develop from the endoderm and yet display several characteristics of a neuronal phenotype. During embryonic life, ductal epithelial cells give rise to first the glugagon-producing cells (alpha-cells) and then cells that express insulin (beta-cells), somatostatin (delta-cells), and pancreatic polypeptide (PP-cells) in a sequential order. The endocrine cells are believed to arise from a stem cell with neuronal traits. The developmental lineage from a common neuron-like progenitor is evidenced by: transient coexpression of more than one cell type-specific hormone in immature cells, expression of neuronal markers during islet cell development, and the pluripotentiality of clones of insulinoma cells to develop into cells expressing other islet cell hormones. The four mature endocrine cell types assume a particular organization within the islets of Langerhans in a process where cell adhesion molecules are involved. In this study we have analyzed the expression of neural cell adhesion molecule (NCAM) and cadherin molecules in neonatal, young, and adult rat islet cells as well as in glucagonomas and insulinomas derived from a pluripotent rat islet cell tumor. Whereas primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons. The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N-cadherin in brain. Insulinoma cells express E-cadherin but differ from primary islet cells by expressing a second cadherin molecule, which is similar to N-cadherin. The expression of NCAM and cadherin isoforms in the glucagonoma suggest that this transformed alpha-cell type has converted to an immature phenotype with strong neuronal traits, reflecting the early palce of glucagon-producing cells in the islet cell lineage. In contrast, insulinoma cells are more islet-like in their phenotype and show less neuronal traits. PMID- 1406711 TI - Citation for the Ernst Oppenheimer Award of The Endocrine Society to James Larry Jameson. PMID- 1406712 TI - Citation for the Richard E. Weitzman Memorial Award to Fred E. Cohen. PMID- 1406713 TI - Citation for the Fred Conrad Koch Award of The Endocrine Society to Melvin M. Grumbach and Selna L. Kaplan. PMID- 1406714 TI - Citation for the Edwin B. Astwood Lectureship of The Endocrine Society to Michael O. Thorner. PMID- 1406715 TI - Citation for the Sidney H. Ingbar Distinguished Service Award to Nettie Karpin. PMID- 1406716 TI - Citation for the Robert H. Williams Distinguished Service Award to Claude J. Migeon. PMID- 1406717 TI - Citation for the Rhone-Poulenc Rorer Pharmaceutical Clinical Investigator Award of The Endocrine Society to Samuel S. C. Yen. PMID- 1406719 TI - Specificity of anti-P25 antibodies produced against whole HIV-1 particles or soluble forms of the protein. AB - Specificity of anti-p25 antibodies produced against either whole Human Immunodeficiency Virus type 1 (HIV-1) particles in humans and chimpanzees, or against soluble forms of the protein in chimpanzees and rabbits was analyzed by ELISA using a panel of 37 long (> or = 30 residues) or shorter (9-21 residues) overlapping peptides covering the entire p25 sequence. Antibodies elicited by intact virions presented similar reactivity patterns in HIV-1-infected humans and in HIV-1-infected or immunized chimpanzees and recognized only a limited region mostly the C-terminus of the molecule. Moreover, 8 of the human sera (36%), which nonetheless reacted with high titers and avidity with native p25, did not bind to any long or short peptide. These results suggest that the majority of antibodies elicited by viral particles are presumably directed to conformational epitopes. In contrast, antibodies raised against soluble forms of p25 could react against all long peptides but one (residues 211-245) and against some short peptides, indicating that most of p25 sequence may be immunogenic under these conditions. These results suggest that the reactivity spectrum of anti p25 antibodies is rather different if they are produced against intact HIV-1 particles or the soluble protein. They also indicate that it may be possible to manipulate the specificity of the humoral immune response by using either intact virions or purified proteins. PMID- 1406720 TI - Characterization of the binding of Bolton-Hunter labeled [125I]C5a to human neutrophil, monocyte and U-937 cell membranes. AB - The fifth component of the complement cascade, C5a, was iodinated using the Bolton-Hunter reagent. Results from the present study, using the high affinity ligand, [125I]Bolton-Hunter-labeled C5a ([125I]BH-C5a), revealed a single binding site on membranes prepared from human neutrophils, U-937 cells and human monocytes. Saturation studies demonstrated Bmax values in these cells of 11.5, 47.3 and 16.6 fmol/10(6) cells, respectively. The C5a receptor demonstrated a very high affinity for [125I]BH-C5a of approximately 4 pM in each cell type. Competition studies using analogs of C5a generated a similar order of potency in each of the cell types of C5a > or = C5a(1-74), Ser66Ala > C5a(1-73) > C5a(1-69). These studies indicate that [125I]BH-C5a labels a similar receptor in neutrophil, U-937 cell and monocyte membranes. Furthermore, C5a(1-73) produced shallow inhibition curves in competition experiments in each cell type. Computer analysis of the binding data revealed two components of binding. When 10 nM unlabeled C5a was used to initiate dissociation of [125I]BH-C5a binding in neutrophil membranes, two binding components were observed. In addition, dissociation of [125I]BH-C5a binding by 10 nM unlabeled C5a in the presence of 1 mM GppNHp decreased the percentage of binding to the slowly dissociating, high affinity binding component from 84 to 58%. These results suggest that multiple states of the C5a receptor exist. PMID- 1406718 TI - CD32A (Fc gamma RIIa) mRNA expression and regulation in blood monocytes and cell lines. AB - The cell surface expression of the CD32 receptors for the Fc portion of immunoglobulin G (Fc gamma RII) is highly regulated by agents such as phorbol ester (PMA) and cytokines. In this study we investigated the regulatory effects of PMA, aggregated IgG (AIgG) and KuFc79 anti-CD32 monoclonal antibodies (mAb) on the expression of the CD32A isomer mRNA. When U937 (CD32+ cells) are incubated with PMA a significant enhancement of the CD32A isomer mRNA is observed. The CD32A mRNA is also markedly enhanced when the CD32+ K562 cells are incubated with AIgG and anti-CD32 mAb but not with control MOPC-195 mAb. The addition of actinomycin D (ActD), a transcriptional inhibitor together with PMA, AIgG or KuFc79 mAb diminishes the enhanced levels of CD32A mRNA to the basal, constitutively expressed levels, implicating transcriptional regulation in this modulatory process. The PMA induced mRNA is rapidly degraded while the constitutively expressed CD32A mRNA is not, suggesting differential regulation of the stimulated vs the unstimulated CD32A mRNA. Inhibition of protein synthesis does not significantly affect the upregulation of CD32 mRNA by PMA, AIgG or KuFc79 in U937 and K562 cells. The upregulation of CD32A mRNA observed in the cell lines U937 and K562 is also detected when normal blood monocytes are used. Similarly to the cell lines the enhancement of CD32A mRNA in monocytes is blocked by ActD. PMID- 1406721 TI - Cold target competition analysis of the classical activation pathway of complement-mediated cytotoxicity: a non-interaction model for competing lysis. AB - A mathematical analysis of cold target competition experiments of complement mediated lysis is presented, aimed at developing a minimal model of lysis where no interaction between the competing populations of sensitized blood group A and B erythrocytes is presumed. The model is able to predict the extent of lysis from the input values with remarkable accuracy suggesting that under the conditions used no stimulation and/or inhibition of the lysis of the sensitized erythrocytes occurs. The distribution of complement between the competing A and B erythrocyte populations is approximated by the model and found to be proportional to the 5th and 4th power of the ratios of the antibody and target cell concentrations, respectively. In accordance with earlier observations, suggesting that the interaction between the antibody and the C1q molecules is based on polar electrostatic charges, we propose that the sensitizing antibody provides an electrostatic field around the erythrocytes which attracts C1q molecules towards their membranes. PMID- 1406722 TI - The same few V genes account for a majority of oxazolone antibodies in most mouse strains. AB - The early primary anti-phenyloxazolone antibodies of 12 mouse strains were studied by determining proportions of two defined subsets id495 (the classical phOx idiotype) and id350. Id495-positive antibodies bear an H chain encoded by VHOx1 gene (family Q52) and an L chain usually coded for by VKOx1 but occasionally by other VK genes. Id350-positive antibodies are encoded by a VK gene VK45.1, and usually by a VH gene of the S107 family. All 12 strains (representing nine H-chain and four kappa-chain haplotypes) produced id350 positive anti-phOx antibodies. While id495 is the predominant major subset in the BALB/c response (originally studied), id350 seems to be the predominant subset of early anti-phOx antibodies in the mouse species. The combined proportion of the two subsets varied from ca. 50 to almost 100% of the total in all strains except C57BL. PMID- 1406723 TI - Monoclonal antibodies to a CD4 peptide derivative which includes the region corresponding to an immunoglobulin CDR3: evidence of the involvement of pre-CDR3 related region in HIV-1 and host cell interaction. AB - A CD4 peptide of amino acid residues 68-130 [CD4(68-130)], which had the capacities to inhibit HIV-1 replication and HIV-1-induced syncytium formation, was used as an immunogen for the preparation of mAb. The mAbs prepared were classified into at least five types (I-V) in terms of their recognition sites by ELISA using various kinds of smaller CD4 peptides. Among them, the type I mAb no. 35 recognizing amino acid residues 72-84, which lies just before the region corresponding to an immunoglobulin third complementarity-determining region (CDR3), showed the strongest effects in reducing both HIV-1 infection and HIV-1 induced syncytium formation, although a large amount of no. 35 mAb was necessary to reduce such HIV-1 activities compared with those of anti-Leu-3a and OKT4A mAbs which recognize CD4 epitopes near a portion corresponding to an immunoglobulin CDR2. Western blot analysis showed that the reactivities of CD4 molecule in CD4 positive cells or sCD4 molecule with types I-V mAbs were stronger than that with anti-Leu-3a mAb. Flow cytometry showed that no. 35 mAb was faintly reactive with native CD4 molecule on cell surface at the concn showing the inhibitory effects on HIV-1 infection and syncytium formation. In addition, a smaller peptide CD4(66 92), one of the good epitope peptides for no. 35 mAb, also showed strong inhibitory effect on HIV-1 infection as well as a weaker inhibitory effect on syncytium formation. These results suggest that, in addition to the CD4 CDR2 related region, the pre-CDR3-related region is also involved in the early events of the interactions between the host cell and HIV-1. PMID- 1406724 TI - Distribution of allergens and allergen-coding mRNAs in various tissues of white birch. AB - The distribution of allergenic proteins was investigated in various tissues of white birch, Betula verrucosa (pollen, leaves and male inflorescences containing immature pollen). In addition, callus and suspension culture cells were investigated for expression of IgE-binding proteins. Furthermore, RNA was extracted from all these tissues and subjected to in vitro translation in a cell free wheat germ system. Bet v I, the major birch pollen allergen, could be extracted easily from pollen, and in low amounts from callus and leaves. No Bet v I could be extracted from immature male inflorescences. Minor allergens were expressed in high concentrations in pollen and in low concentrations in immature male inflorescences. No minor allergens could be detected in callus and leaves. In contrast to these observations, RNA from all the tissues as well as from callus could be translated in vitro into Bet v I as well as into minor allergens, in particular birch profilin (Bet v II), an important minor allergen. These data suggest that IgE-binding proteins of B. verrucosa, especially Bet v I, under certain circumstances can readily be synthesized in tissues other than pollen. This concept is corroborated by the recent observation that Bet v I reveals high homology with disease resistance response gene products from other plants, suggesting a similar function of Bet v I for the birch. PMID- 1406725 TI - Genomic organisation and sequence of the extracellular domain exons of the bovine Fc gamma RI receptor, and evidence for restricted binding of ruminant IgG to U937 cells. AB - Southern blotting of bovine genomic DNA and hybridization with a human Fc gamma RI cDNA probe, p135, has identified a single copy of the bovine Fc gamma RI gene. A bovine genomic lymphocyte library in lambda EMBL3 was screened with probe p135. A positive lambda clone, 15.5.4, containing the three extracellular domain exons of Fc gamma RI, has been cloned, mapped and sequenced. Each extracellular domain is encoded within a single exon. All three domains are assigned to the C-2 set of the Ig superfamily with 58% identity between amino acid residues of bovine, human and mouse Fc gamma RI. Pairs of cysteine residues are conserved in each domain as potential sites for intra-chain disulphide bonding. Human monocytoid U937 cells were used as a model to test binding homology within the Fc gamma RI family. The binding of IgG isotypes to IFN-gamma stimulated U937 cells was determined by FACScan flow cytometry. U937 cell Fc gamma RI receptor does not bind bovine or ovine IgG isotypes. On the basis of these studies and by comparison of the Fc determinant region sequences of IgG, the introduction of species specificity in Fc gamma RI/IgG interaction by evolutionary drift is proposed. PMID- 1406726 TI - Sensitive non-radioactive detection of HIV-1: use of nested primers for the amplification of HIV DNA. AB - This report describes the use of the polymerase chain reaction (PCR) for the non radioactive detection of HIV-1 proviral genomic sequences in HIV-1 infected cells. We have developed a sensitive assay, using three different sets of nested primers and our results show that this method is superior to standard PCR for the detection of HIV-1 DNA. The assay described features the use of a simple and inexpensive sample preparation technique and a non-radioactive hybridization procedure for confirmation of results. To test the suitability of the assay for clinical purposes, we tested cell samples from 76 anti-HIV-1 positive patients. All were positive for at least one primer set: 88% were positive for all three sets of primers; 9% were positive for two sets of primers and 3% were positive for only one set of primers. It provides a useful approach to the study of HIV-1 infection in patient samples where genomic copies often are present at such low numbers that they are otherwise undetectable. PMID- 1406727 TI - Generation of digoxigenin-labelled double-stranded and single-stranded probes using the polymerase chain reaction. AB - As the polymerase chain reaction (PCR) can be used for the generation of vector free probes, the optimum conditions for incorporation of digoxigenin-11-dUTP into hepatitis B virus (HBV) probes have been investigated. High yields of double stranded or single-stranded probes can be obtained by utilizing a pair of primers or one primer alone. The probes were tested by dot-blot hybridization on HBV plasmid DNA, slot-blot hybridization on total cellular RNA of Alexander cells and Southern blot hybridization on cellular DNA of Alexander cells and HBV plasmid DNA. They were also tested by in situ hybridization (ISH) on HBV-positive biopsy liver tissue. A ratio of dig-dUTP:dTTP of 1:3 gave highest sensitivity in DNA hybridization. No loss of amplification efficiency and sensitivity was observed when the final concentration of dig-11-dUTP and dTTP was reduced to 20 microM and 60 microM respectively, compared to 200 microM each of dATP, dCTP, dGTP. Several different sizes of double-strand probes were compared by dot-blot hybridization. Longer probes were more sensitive. Strong signal could also be obtained by combination of two or three small probes, which have overlapping sequences. Single-stranded DNA probes had advantages of simplicity of use, high sensitivity and strand specificity. PMID- 1406728 TI - Colorimetric detection of Plasmodium falciparum and direct sequencing of amplified gene fragments using a solid phase method. AB - A rapid colorimetric assay for the detection of DNA from Plasmodium falciparum malaria is described, allowing direct sequencing of amplified fragments in the positive samples. The method is based on amplification by the polymerase chain reaction (PCR), with incorporation of biotin and a lac operator sequence in the amplified target DNA. The PCR product was immobilized on streptavidin-coupled magnetic beads, and detected by the specific binding of an Escherichia coli lac repressor beta-galactosidase fusion protein. Positive samples were subsequently treated with alkali to generate single stranded templates, which were used for solid phase genomic sequencing. As targets for amplification and sequencing we selected a region of the gene for the antigen Pf155/RESA and a region of the parasite dihydrofolate reductase gene (PfDHFR/TS). We show here that both of these gene targets can be used for specific detection of P. falciparum in patient blood samples. Genomic sequencing of five patient isolates revealed no variation in the Pf155/RESA gene fragment. In a comparison of this sequence with conserved protein domains, a marked similarity to the src homology region 3 was detected. A point mutation was found in the PfDHFR/TS gene fragment of one of the clinical samples, replacing Ser108 with Asn. This mutation has earlier been described in pyrimethamine and cycloguanile-resistant strains of P. falciparum. PMID- 1406729 TI - Identification of Shiga-like toxin type II producing Escherichia coli using the polymerase chain reaction and a digoxigenin labelled DNA probe. AB - Epidemiological studies have demonstrated that enterohaemorrhagic strains of Escherichia coli which cause the haemolytic uremic syndrome in humans and the oedema disease in pigs more frequently produce Shiga-like toxin type II (SLT-II) than any other member of the Shiga-like toxin family. A technique has been developed for the identification of SLT-II producing E. coli using the polymerase chain reaction (PCR) and a digoxigenin (DIG)-labelled DNA probe to facilitate the early detection and epidemiological analysis of these pathogens. Whole cell DNA liberated from isolated colonies during the denaturation step of PCR was amplified using a primer pair which is homologous to the slt-II gene sequences. The amplification products were transferred directly to a nitrocellulose membrane or following agarose gel electrophoresis and DNA denaturation. A chemically labelled DNA probe, prepared using PCR with the incorporation of DIG, was used to identify the PCR products of strains which produced SLT-II or a variant of SLT II. PMID- 1406731 TI - Effects of post-mortem autolysis on the detection of rabies virus genomic RNA and mRNA in mouse brain by using in situ hybridization. AB - The effects of post-mortem autolysis were studied on the detection of rabies virus RNA in the brains of mice with experimental rabies by using in situ hybridization (ISH). The brains of CVS-infected mice were subjected to autolytic periods in situ of up to 72 h. ISH was performed with 3H-labelled RNA probes for rabies virus glycoprotein gene genomic RNA and mRNA. During the post-mortem period there was progressive loss of signals for genomic RNA and mRNA, which was greater for mRNA. ISH signals in perikarya also changed for genomic RNA from a multifocal to a diffuse distribution during the post-mortem period. Rabies virus antigen was better preserved during the autolytic period. Effects of the agonal state, degradation of RNA by ribonucleases, and diffusion of RNA out of cells prior to fixation could explain the loss of ISH signals in post-mortem tissues. PMID- 1406730 TI - Quantification of sensitive non-isotopic filter hybridizations using the peroxidase catalyzed luminol reaction. AB - The development of a sensitive, non-isotopic filter hybridization method based on the peroxidase catalyzed luminol reaction is described. High sensitivity was achieved by optimizing the conditions of the hybridization procedure, the immunochemical detection and the peroxidase/luminol reaction. This resulted in the reproducible detection of 10-30 femtogram of target DNA on blots within minutes when a cooled charge coupled device (CCD) camera was used to record the luminescence signal. After optimalization, the system was successfully applied for the qualitative and quantitative analysis of small amounts of DNA in dot blots as well as in Southern blot analysis. PMID- 1406732 TI - PCR amplification of mini-exon genes differentiates Trypanosoma cruzi from Trypanosoma rangeli. AB - Synthetic oligonucleotides corresponding to a conserved 22 nucleotide sequence within the tandemly repeated mini-exon gene have been used to amplify a single gene-containing repeat from Trypanosoma cruzi and Trypanosoma rangeli, two morphologically similar organisms with overlapping hosts and geographical distribution but different pathogenicity in humans. The T. cruzi repeat is 582 nucleotides long and the T. rangeli repeat is 858 nucleotides. The two organisms may therefore be distinguished primarily by the electrophoretic mobilities of their respective amplification products. Confirmation of the diagnosis can be obtained by Southern blot analysis using species-specific DNA probes from the unique intergenic regions. We also present a diagnostic assay in which the unique intergenic regions are immobilized on nylon membranes and differentiation is based on hybridization with a digoxigenin-labelled PCR product. PMID- 1406733 TI - Comparison of spot-blot and microtitre plate methods for the detection of HIV-1 PCR products. AB - We have compared spot-blot methodology with a recently developed rapid microtitre plate assay for the specific detection of HIV-1 PCR products. We have studied blood specimens isolated from HIV-1 infected individuals (48 asymptomatic and 56 symptomatic patients). Mononuclear cells were isolated, lysed and processed for PCR. Both PCR product detection methods were carried out in parallel on all amplified samples. HIV-1 sequences were detected by spot-blot or microtitre plate hybridization in samples taken from 42/48 asymptomatic and 53/56 symptomatic subjects. Concordant results between the two detection methods were observed for 90 samples, with 81 positive and nine negative assays. On repeat evaluation of the 14 discordant samples, nine showed concordant positive results, near the limit of detection of the assay. Serial dilutions of ACH-2 cells were amplified, and the PCR products were detected using the microtitre plate assay, yielding semi-quantitative results. The sensitivity of this simple, rapid assay compares with that of more laborious DNA detection systems. This may become a useful tool in HIV-1 research and in the clinical care of seropositive individuals. PMID- 1406735 TI - Arrangement of DYZ1 and DYZ2 repeats on the human Y-chromosome: a case with presence of DYZ1 and absence of DYZ2. AB - The composition of Yq-heterochromatin is dominated by the two repetitive sequences DYZ1 (4000 copies) and DYZ2 (2000 copies). Probes derived from these sequences can be used for sex determination and the structural analysis of aberrant Y-chromosomes. Using such probes Schmid et al., have recently proposed a regular interspersion of the two sequences in a ratio of 2:1 over the entire Yq12 chromosome region. By Southern analysis we investigated the DNA of a normal male, cytogenetically negative for Yq-heterochromatin. Applying the same probes as used by Schmid et al., only a small amount of DYZ1 material could be detected. The case presented indicates the presence of DYZ1 only in the Yq11-Yq12 junction region and excludes DYZ2 from any function relevant for normal male development. PMID- 1406734 TI - Use of modified nucleotides and uracil-DNA glycosylase (UNG) for the control of contamination in the PCR-based amplification of RNA. AB - The inadvertent carryover of amplified fragments of nucleic acids (amplicons) is a potential source of contamination in the polymerase chain reaction. Recently, a method has been developed to generate amplicons with deoxyuracil triphosphate (dUTP) and to specifically hydrolyze these amplicons with uracil-DNA glycosylase (UNG) following the completion of the assay. We evaluated this system for the specific amplification of RNA from coxsackievirus A3 and B3. We found that RNA from both viruses could be amplified with dUTP, although the use of this triphosphate in place of TTP resulted in some loss of assay sensitivity. We also found that the dUTP-containing amplicons could be efficiently hydrolyzed by UNG, resulting in a 10,000,000-fold reduction in amplicon concentration with little effect on the native nucleic acid. The dUTP-UNG method has a great deal of potential for reducing amplicon contamination during the routine performance of nucleic acid amplification reactions. PMID- 1406736 TI - [Exosurf-Neonatal: the synthetic surfactant. Introductory symposium, 20 June 1992]. PMID- 1406737 TI - Kash Mostofi, M.D.: a tribute. PMID- 1406738 TI - Image analysis and flow cytometry of tumors of prostate and bladder; with a comment on molecular biology of urothelial tumors. PMID- 1406739 TI - The prostate--overview: recent insights and speculations. PMID- 1406740 TI - Controversies in prostate pathology: dysplasia and carcinoma in situ. AB - In recent years we have made great strides in our understanding of various atypical lesions within the prostate. This clarity originated with the recognition that lesions of atypical hyperplasia of the prostate are diverse both in their histology and in their potential relationship to adenocarcinoma. While the possible relationship of adenosis to carcinoma is still somewhat controversial, there has been a growing body of histological, histochemical, and immunohistological evidence demonstrating that intraductal dysplasia (PIN) is closely linked to some forms of adenocarcinoma of the prostate. Whether there are significant differences in the relationship of intraductal dysplasia to clinically detectable peripherally located adenocarcinoma and centrally located incidentally found carcinomas needs additional clarification. Further studies on all forms of atypical hyperplasia are still required to determine their relative risk of developing carcinoma, similar to those that have been recently published on various atypical hyperplastic lesions within the breast. In order for these studies to be successful, better imaging techniques of the prostate must become available to rule out invasive carcinoma already being present when one of the forms of atypical hyperplasia is identified on biopsy. Additional directions of research in the future will also undoubtedly probe the molecular biology of various forms of atypical hyperplasia, in particular intraductal dysplasia and its relationship to carcinoma, although at this time the molecular characteristics of adenocarcinoma of the prostate is still in its infancy. PMID- 1406741 TI - Diagnostic correlations with whole mounts of radical prostatectomy specimens. AB - While probably not necessary in routine diagnosis, whole-mount sections of radical prostatectomy specimens can provide valuable information that is difficult to obtain by other means. Contrary to popular belief, the technique can be carried out in the routine histology laboratory with only minor modifications of existing methods. The use of this technique has provided valuable insight into the tumor biology of early stage prostatic cancer pointing to a multifocal origin for this disease. Likewise, the study of tumor volume, histological grade, and capsular penetration has provided a basis for the use of such prognostic markers in clinical management. The continuing development of new screening tools such as TRUS and MRI requires careful correlation with histopathology to assure a fundamental understanding of their abilities and limitations to detect and stage early-stage tumors. Only with such continued effort will diagnosis and clinical intervention allow us to make a meaningful impact on the natural history of this common malignancy. PMID- 1406742 TI - The biology of prostate cancer: new and future directions in predicting tumor behavior. AB - Because the present ability to treat and cure patients with prostate cancer is limited to those patients with pathologically organ-confined disease, it has become increasingly important to diagnose this disease at an early stage when cure is most likely. Recent advances in imaging may allow the urologist and pathologist to make the diagnosis of prostate cancer much earlier in the natural course of the disease. It therefore becomes imperative to have methods available to predict which patients have a high probability of progressing so that treatment can be assigned logically and appropriately. Our current methods of prognosis determination (stage and grade) do not allow accurate assessment of tumor behavior in the majority of individual patients with prostate cancer. Therefore, more accurate quantification of nuclear and cellular changes that take place as a tumor progresses to take on the aggressive (metastatic) phenotype are urgently needed. Experimental techniques have proven useful in answering these questions in animal models and now seem ready for large-scale testing in clinical studies. PMID- 1406743 TI - Significant nonmalignant proliferative and neoplastic lesions of the urinary bladder. PMID- 1406744 TI - Genetics of tumorigenesis and multidrug resistance in urinary bladder cancer. PMID- 1406745 TI - Urothelial neoplasia. AB - Urothelial neoplasia is a complex subject that can be only partially understood by careful study of the light microscopic features of individual lesions. Despite decades of study, our knowledge concerning the interaction of neoplastic events and host responses remains rudimentary. Most information has been collected by observing cases (usually in retrospect) that have been grouped according to relatively arbitrary criteria based on the phenotypic appearances of lesions as they are viewed through the light microscope. When evaluating human disease, we are always forced to reason backwards to determine the most likely histogenesis and to project forward to assess the most likely prognosis. Both types of reasoning must be filled with conjecture since direct observations from the initial events to the end results are not possible. Under these constricting circumstances, a conceptual framework into which our often anecdotal observations can be placed is more important than we would like to admit. With this in mind, I have taken advantage of the monograph format to risk a speculative approach to the subject, at least as it applies to the significance of the pathological features. In the past, we have accepted the view that all human hosts are essentially the same and that variations in cancer type and behavior are related almost entirely to the genetic ingenuity of the cancer cells themselves. Perhaps we should now entertain the opposite view, that carcinogenic events are ubiquitous and that cancer in any individual patient represents only what that patient will allow to grow in his or her body. We have devoted almost all of our collective research energy to examining the tumor. I believe that the pace of future progress can be significantly increased if we can think of more ways to examine the patient. PMID- 1406746 TI - Adrenergic receptors in hypertension and heart failure. PMID- 1406747 TI - Newer aspects of neuroendocrine control in heart failure. PMID- 1406748 TI - Pathophysiology and treatment of hypertensive heart disease. PMID- 1406749 TI - Management of malignant ventricular tachyarrhythmias. PMID- 1406750 TI - Graves' disease and its retroorbital aspects. AB - Graves' disease is a common, familial, but easily treated condition caused by unique autoantibodies which act as TSH agonists. Patients with the diagnostic eye signs of Graves' disease, however, require more careful treatment than those patients with principally thyroidal involvement because destructive therapy to the thyroid gland may exacerbate the eye disease. The cause of ophthalmic eye disease appears to be "crossover specificity" by the immune system for a recurrent antigen in extraocular muscles, fibroblasts, and the thyroid gland. Treatment directed at the autoimmune response may offer the most appropriate therapy in the years to come. PMID- 1406751 TI - Established and new uses of intravenous immunoglobulin. AB - We know much about the biologic activities of the immunoglobulin molecule. We know its structure, and much about its function. However, I think that surprises are still ahead of us. As we become more familiar with what the immunomodulation doses of IVGG can do, I think we will find other uses of IVGG relying on antiidiotypic antibodies and possibly other cell-mediated functions. PMID- 1406752 TI - The art of the gastrointestinal consultation: some aphorisms. PMID- 1406753 TI - Clinical and genetic associations in Marfan syndrome and related disorders. AB - Although Marfan syndrome has been a recognized clinical entity for nearly a century, only in the early 1950s were its manifestations and genetic features firmly and fully established. Similarly, although the identification of the basic defect in Marfan syndrome had been vigorously pursued for several decades, it was only in 1991 that two independent reports implicated fibrillin as the defective gene product. Surprisingly and serendipitously, these studies also revealed genetic heterogeneity of the fibrillin proteins and established linkage between one of these loci and a Marfan-related disorder, congenital contractural arachnodactyly. Like Marfan syndrome, this condition is accompanied by skeletal abnormalities; however, flexion joint contractures replace the loose-jointedness of Marfan syndrome and, more importantly, neither the eye nor the aorta are affected. More recently, a similar association with the fibrillin gene has also been established in the dominantly inherited form of ectopia lentis. These associations of structurally related gene products with Marfan and related syndromes may conceivably imply that other connective tissue disorders are caused by mutations in these or other yet undiscovered fibrillin genes. PMID- 1406754 TI - Epicardial cryoablation of myocardial tissue using endocardial thermal isolation. AB - Surgical cure of right atrial arrhythmias may be accomplished by excision, exclusion, or cryoablation of the arrhythmogenic focus. Cryoablation may be performed epicardially without cardiopulmonary bypass but carries an operative recurrence rate of 57%. Successful cryoablation of a right atrial arrhythmia requires the reliable creation of transmural tissue necrosis. Heat transferred to the endocardium from normothermic circulating blood in the atrium or within the atrial wall may prevent full-thickness, lethal freezes. This study demonstrates that compression of myocardial tissue between an external cryoprobe and an endocardial template produces endocardial thermal isolation of the target area by displacing warm solutions from the endocardium. This is essential to achieve consistently lethal transmural freezes of -60 degrees C. Use of this technique may reduce the high operative recurrence rate of right atrial tachycardias treated with conventional cryoablation techniques. PMID- 1406755 TI - Endometriosis causing colon obstruction in two postmenopausal women. AB - Colonic endometriosis is an uncommon lesion usually found in premenopausal women. We describe two postmenopausal women with colonic endometriosis that resulted in colonic obstruction. One of the women was receiving estrogen-replacement therapy. Colonic endometriosis in postmenopausal women may become more common as the population ages and the use of long-term estrogen-replacement therapy becomes increasingly widespread. PMID- 1406756 TI - Ileocecal tuberculosis in an Asian male immigrant: case report and literature review. PMID- 1406757 TI - [Isolation and purification of Brucella antigens synthesized by Escherichia coli K12 cells]. AB - The homogeneous preparations of the brucella protein antigens were isolated from the hybrid producer strains Escherichia coli 6SE579 and 6SE800 by the cold osmotic shock technique and further purification on immunosorbents. The 18 + 38 and 38 kDa antigens were obtained. The antiserum specific to brucella 38 kDa antigen was obtained and used for isolation of the 18 kDa antigen from the producer strain 6SE579 synthesizing two brucella antigens. The immunosorbent developed on the basis of BrCn-agarose conjugated with antibodies from the serum has permitted isolation of 18 kDa protein antigen preparation. Thus, the combined technique of cold osmotic shock and affinity chromatography on immunosorbents permits one to isolate highly purified individual antigens of brucella from Escherichia coli K12 producer cells. PMID- 1406758 TI - [Plasmid heterogeneity in populations of Yersinia pestis strains]. AB - Yersinia pestis strains with the typical plasmid patterns were shown to have the heterogenic populations. Heterogeneity is increased by cultivation passages in artificial nutrient media and is manifested in plasmid elimination within several clones, plasmid integration into the chromosome, appearance of auxiliary plasmids or the ones with increased molecular masses. Passages of strains in experimental animals result in populations homogeneity with the typical plasmid patterns within all clones tested. The clones having changed the plasmid content and selected from heterogenic populations pertain their properties when cultivated in nutrient media and passaged in experimental animals. PMID- 1406759 TI - [Mu-induced deletions and mutations of Erwinia carotovora chromosomes, including resident prophages E105 and 59]. AB - The plasmid RP4::Mu cts62 in stably inherited by Erwinia carotovora 268 strain. Under the conditions of thermoinduction bacteriophage Mu is segregated and completely eliminated more intensively than in Escherichia coli cells. At thermoinduction the transposition of bacteriophage Mu cts62 into different chromosomal sites takes place, causing the induction of chlorate resistant and auxotrophic mutants with the frequency of 10(-4). Two clones deficient in production of 2 of the 4 resident prophages of Erwinia carotovora 268 strain were found among Mu-induced mutants. The deleted prophages are E105 and 59. DNA-DNA hybridization has revealed the complete and partial deletions of bacteriophage E105 with the level of L-asparaginase production in the cells remaining intact. The damage of the prophage 59 is probably caused by point mutations or short deletions. PMID- 1406760 TI - [Preparative isolation of basic structural proteins of the influenza virus]. AB - The schemes for preparative electrophoretic isolation and purification of major proteins from influenza virus are described. The viral envelope protein, hemagglutinin, two of its subunits, internal M and NP proteins of influenza viruses A/FPV/Rostock (H7N1), A/PR/8/34 (H1N1) and X-31 (H3N2) were obtained in preparative amounts and characterized by amino acid and N-terminus analyses. PMID- 1406761 TI - [Determination of the effectiveness of RNA cross-linking with protein induced by UV-radiation in potato X-virus particles]. AB - The UV-irradiation was found to induce formation of the RNA-protein cross-links and intraviral RNA chain breaks in the particles of flexuous potato virus X (PVX). Using the technique developed previously for the rod-like tobacco mosaic virus (TMV), the quantum yields of RNA-protein cross-links and intraviral RNA polynucleotide chain breaks formation in the PVX were determined and found to be more or less close to those found for the intraviral TMV RNA. PMID- 1406762 TI - [Restriction analysis of Thiobacillus ferrooxidans DNA using pulsed field electrophoresis]. AB - The DNA of Thiobacillus ferrooxidans digested by any of the five restriction endonucleases (DraI, EcoRI, Eco321, HindIII, XbaI) was studied by electrophoresis in the pulsating differently directed electric fields (PF). The influence of PF conditions on the sized row of the divided DNA fragments was studied. Only the XbaI restriction endonuclease was shown to cleave the Thiobacillus ferrooxidans DNA into a number of fragments permitting one to define the sizes of fragments and genome (no more than 2300 bp). The prospects of using the restriction analysis of Thiobacillus ferrooxidans wild type culture for improving its properties in obtaining heavy metals are discussed. PMID- 1406763 TI - Improvement of the exercise test after therapy in thyrotoxic periodic paralysis. AB - The diagnosis of periodic paralysis (PP) can be aided by demonstrating a decrease in compound motor action potential (CMAP) amplitude after several minutes of exercise. We report a case of secondary hypokalemic PP due to thyrotoxicosis in which the decrease in the CMAP amplitude after exercise dramatically improved after treatment, when a euthyroid state was achieved. The exercise test is a useful electrophysiologic means of monitoring the neuromuscular status of patients with thyrotoxic periodic paralysis prior to, and after treatment of the thyrotoxicosis. PMID- 1406764 TI - The spectrum of concentric macro EMG correlations. Part I. Normal subjects. AB - Using a concentric macro electrode, both the concentric and macro action potentials of a motor unit were analyzed for duration, area, and amplitude. Eighty-six different motor units were analyzed from the tibialis anterior muscle in 10 normal subjects. The aim of this work was to compare concentric and macro action potential measurements of the same motor unit. The study revealed significant correlations between concentric and macro samples, with the concentric potential's area correlating better with the macro potential than its amplitude. This shows that the 10 to 15 muscle fibers studied by the concentric electrode serve as a good sample of the motor unit as a whole. We briefly review the technique used in concentric macro EMG, as well as describe the methods used for collecting and comparing both concentric and macro action potentials. PMID- 1406765 TI - The spectrum of concentric macro EMG correlations. Part II. Patients with diseases of muscle and nerve. AB - In the second part of this study we investigate the correlations between the concentric and conmac action potentials in motor units of individuals with diseases of muscle and nerve. We studied 86 myopathic and 86 neurogenic motor units and compared their concentric and conmac action potentials. In the patients with myopathy, we found that the concentric motor unit action potential's (MUAP) area correlates strongly with the conmac potential, even better than in normals, while its amplitude correlates less. In the neurogenic group, we found that both the concentric MUAP's area and amplitude correlated very well with their conmac counterpart, more so than in normals. Thus, in pathology, as in normals, measuring the concentric MUAP's area in addition to its amplitude adds to the diagnostic sensitivity of motor unit potential measurements. These findings are discussed in light of the known dynamic and architectural motor unit changes which take place in the myopathic and neurogenic motor unit. PMID- 1406767 TI - Differential expression of muscular dystrophy in diaphragm versus hindlimb muscles of mdx mice. AB - Contractile properties of diaphragm (DIA) from mdx and control mice were compared with those of hindlimb muscles [soleus (SOL) and extensor digitorum longus (EDL)] in vitro. Mice ranged in age from 2 weeks to 1.5 years. Muscles were directly stimulated and properties measured were: contraction time, half-relaxation time, active tension per unit area, fatigue index, and maximal velocity of shortening (Vmax). Active tension decreased significantly with age in mdx DIA but not in control DIA. SOL and EDL active tensions were less in mdx than control over the whole age range and did not decrease with age. Vmax was decreased in mdx DIA, but not in mdx SOL or EDL. These results demonstrate that DIA is more affected by muscular dystrophy than hindlimb muscles. Since many Duchenne patients exhibit respiratory distress, this differential expression of dystrophy in diaphragm, as compared to limb muscles, may have important clinical implications. PMID- 1406766 TI - Effects of age, sex, and anthropometric factors on nerve conduction measures. AB - Associations among measures of median, ulnar, and sural nerve conduction and age, skin temperature, sex, and anthropometric factors were evaluated in a population of 105 healthy, asymptomatic adults without occupational exposure to highly repetitive or forceful hand exertions. Height was negatively associated with sensory amplitude in all nerves tested (P less than 0.001), and positively associated with median and ulnar sensory distal latencies (P less than 0.01) and sural latency (P less than 0.001). Index finger circumference was negatively associated with median and ulnar sensory amplitudes (P less than 0.05). Sex, in isolation from highly correlated anthropometric factors such as height, was not found to be a significant predictor of median or ulnar nerve conduction measures. Equations using age, height, and finger circumference for prediction of normal values are presented. Failure to adjust normal nerve conduction values for these factors decreases the diagnostic specificity and sensitivity of the described measures, and may result in misclassification of individuals. PMID- 1406768 TI - Nerve conduction studies in amyotrophic lateral sclerosis. AB - Nerve conduction studies (NCS) are an integral part of the evaluation of amyotrophic lateral sclerosis (ALS) patients and are useful in distinguishing ALS from disorders that mimic it. The question often arises whether in the presence of severe atrophy and reduction of the compound muscle action potential amplitude, abnormal conduction velocity (CV), distal latency (DL), or F-wave latency (F) exceeds what can be expected from ALS alone. To determine the limits of abnormality in classic ALS, we prospectively evaluated NCS data from 61 patients who met a strict clinical definition of ALS. We related CV, DL, and F to distal evoked amplitude (AMP) in peroneal (n = 63 observations), median (n = 50), and ulnar (n = 52) nerves. In nerves with reduced AMP, CV rarely fell to less than 80% of the lower limit of normal, and DL and F rarely exceeded 1.25 times the upper limit of normal. Utilizing the entire data set and regression analyses, 95% confidence limits for expected values for CV, F, and DL as a function of AMP were calculated. These limits thus derived suggest criteria for NCS abnormalities in ALS and may be useful in differentiating ALS from other illnesses. PMID- 1406769 TI - Mild ischemia causes severe pathological changes in experimental diabetic nerve. AB - Nerve ischemia is considered one of etiological factors in the development of structural changes in peripheral nerves associated with diabetes mellitus. To assess the effect of mild ischemia on diabetic nerve, a subthreshold dose of polystyrene microspheres was injected intraarterially to occlude microvessels of the sciatic nerve and its branches in 20-week streptozotocin-induced diabetic and control rats. Diabetic sciatic and tibial nerves showed severe pathological change of myelinated fibers, whereas nondiabetic nerves were normal or had minor structural abnormalities. Morphometrical evaluation confirmed a greater frequency of abnormal myelinated fibers in diabetic nerves especially in central fascicular regions. The results indicate that diabetic nerve has an increased morphological susceptibility to nerve ischemia. Endoneurial hypoxia, which may result from hemorheological and vascular abnormalities, is likely to cause a lowered threshold to ischemic tolerance in diabetic nerve. This increased vulnerability to ischemia may render diabetic nerve unduly susceptible to hyperglycemia-induced systemic tissue abnormalities. PMID- 1406770 TI - Neuromuscular responses of patients with multiple sclerosis. AB - Muscle weakness, studied in 4 patients with multiple sclerosis (MS), was compared with values from normal subjects. Twitch occlusion showed that normal subjects could activate their muscles maximally, but patients rarely achieved greater than 60% activation. In both groups, motoneuron firing rates increased linearly with force. Consistent with the reduced level of activation, MCV firing rates in MS muscles rarely exceeded 17 Hz (compared with approximately 24 Hz for normals). However, for right and left muscles of one patient, mean maximum firing rates were 14.2 +/- 2 Hz and 8.0 +/- 2 Hz, but her muscles, could be activated to levels greater than 92% and 60%, respectively. This patient's ability to achieve higher than expected forces at low firing rates was probably due to her slow muscle contractile speeds, especially 1/2-relaxation time (75 to 115 ms, cf. approximately 60 ms for normals), and high twitch/tetanus ratio (0.4, cf. 0.2). PMID- 1406771 TI - F waves and motor unit size. AB - M responses and twitch contractions were evoked in single motor units (MUs) of the first dorsal interosseus muscle by intramuscular microstimulation of motor axons. Two-hundred nine MUs were studied in 21 subjects. Thirty-five MUs (17%) showed F waves in addition to M responses. Twitch force was used to provide an indirect measure of MU size; additionally, twitch contraction time was measured. There was no select group of MUs generating F waves with regard to the above contraction parameters. However, four of five MUs with very high twitch forces, above 70 mN, generated F waves. We conclude that MUs of all sizes produce F waves with similar probability. Only few MUs with very strong twitch forces, i.e., very large MUs, may be more subject to F-wave production and may be involved in the generation of the so-called repeater F waves. PMID- 1406772 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Clinical measures. PMID- 1406773 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Morphological and biochemical measures. PMID- 1406774 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Electrodiagnostic measures. PMID- 1406775 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Quantitative sensory testing. PMID- 1406776 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Summary and recommendations. PMID- 1406777 TI - Myoblast transfer in DMD: problems in the interpretation of efficiency. PMID- 1406778 TI - Mitochondrial abnormalities in oculopharyngeal muscular dystrophy. PMID- 1406779 TI - Anorectal incontinence in myotonic dystrophy: a myopathic involvement of pelvic floor muscles. PMID- 1406780 TI - Is acute axonal form of Guillain-Barre syndrome a primary axonopathy? PMID- 1406781 TI - The really safe neurologist's pin--wooden toothpick. PMID- 1406783 TI - Shiatsu massage-induced injury of the median recurrent motor branch. PMID- 1406782 TI - Laryngeal dystonia in multiple system atrophy. PMID- 1406784 TI - Oral candidosis: treatment with absorbable and non-absorbable antifungal agents in children. AB - Oral candidosis in neonates and children is a common infection which occurs often during the first few months after birth, but occasionally also in older children with certain predisposing factors. In neonates, oral candidosis is usually benign, although the symptoms of such an acute infection can be disturbing to both the patient and the parents. In older children developing oral candidosis, specific predisposing factors may be present (e.g. immunodeficiency, chemotherapy, etc.). In such cases, the infection may constitute a source for further dissemination, leading to occasionally fatal Candida sepsis or to widespread chronic mucocutaneous candidosis. Treatment modalities to date include drugs with limited or no absorption from the gastrointestinal tract (e.g. nystatin and miconazole) and agents that are absorbed, combining local effect with systemic therapy (e.g. clotrimazole, ketoconazole, itraconazole and fluconazole). Overall, it appears that treatment of neonatal oral candidosis should be performed with non-absorbable drugs, while the systemically active agents should be used primarily if a risk of dissemination exists or if widespread disease is present. In general, side-effects and toxicity are not major causes of concern with non-absorbed or absorbed antifungals in children with oral candidosis, since treatment is usually of relatively short duration. When the systemically active agents are used in premature infants with sub optimal liver function, the risk of drug-induced liver toxicity may be increased. PMID- 1406785 TI - Melanized and non-melanized multicellular form mutants of Wangiella dermatitidis in mice: mortality and histopathology studies. AB - One melanized (Mc3) and one non-melanized (Mc3W) multicellular form mutant of W. dermatitidis were compared with parental wild type in NYLAR mice. Each mutant grows as multicellular (muriform-like) forms in vitro at 37 degrees C and as yeasts at less than or equal to 30 degrees C. Yeast cells of all three strains were injected intravenously at concentrations of 1 x 10(4), 1 x 10(6), 1 x 10(7), 3 x 10(7) and 1 x 10(8) cells/mouse in groups of 10 mice. There was no virulence difference between wild type and Mc3, with 100% mortality obtained with each strain at greater than or equal to 1 x 10(7) cells/mouse. In contrast, Mc3W was less virulent, with mortality being obtained only at 1 x 10(8) cells/mouse. Histopathological study of brains, lungs, livers and spleens of moribund mice revealed that both Mc3 and Mc3W persisted in tissue as muriform cells, and in some cases as yeast, pseudohyphal and hyphal forms. There was no major difference between Mc3 and Mc3W in terms of histopathological response. These data support the association between melanin and virulence in W. dermatitidis and provide a model for the study of muriform cells in vivo. PMID- 1406786 TI - Fungal infections following heart transplantation. AB - Following heart transplantation (HTx), patients often suffer from mycoses due to the necessary immunosuppressive treatment to prevent rejection episodes. Oropharyngeal Candida infections which mostly occur after HTx under high-dose immunosuppressive therapy can be avoided and treated successfully by prophylactic medication to be started immediately after transplantation, either by using azoles (e.g. fluconazole) or amphotericin B suspension. Contrary to this, invasive aspergillosis, beginning in the upper respiratory tract and the lung and mostly followed by hematogenous dissemination into various organs, is always a serious disease with high mortality. To avoid this infection, specimens from the respiratory tract, serum and urine should be examined mycologically prior to HTx. After HTx, apart from prophylactic avoidance of exposure to airborne fungal spores, close mycological control is mandatory to detect colonizations by aspergilli early. Timely administration of amphotericin B and 5-flucytosine, i.e. as soon as invasive growth is suspected, enables curative treatment of the often lethal course of this disease, even under immunosuppressive therapy. PMID- 1406787 TI - Tissue response in sporotrichosis: light and electron microscopy studies. AB - On the basis of electron microscopy examination of human tissue affected by sporotrichosis, we have proposed a classification, at the light microscopy level, of fungal cells in tissue. Light and electron microscopy observations clarified the following five points: (1) in sporotrichosis lesions in man, the fungal cells are frequently phagocytized by polymorphonuclear leucocytes (PMNs); (2) phagocytosis of phagocytes by other phagocytes was common, and giant cells phagocytized both fungal cells and PMNs; (3) fungal cells in the tissues of lesions were thought to be highly viable, and their budding was frequently observed within macrophages and giant cells; (4) it was highly probable that PMNs participated in asteroid body formation; (5) few free fungal cells were present in the tissues. We believe that the classification of fungal cells in sporotrichosis tissue into the five categories below is useful for correctly understanding the pathological condition in a sporotrichosis lesion: (1) fungal cells in PMNs, (2) fungal cells in PMNs within macrophages, (3) fungal cells in macrophages, (4) fungal cells in giant cells, and (5) free fungal cells. PMID- 1406788 TI - Symmetrical deforming cutaneous sporotrichosis of long duration. AB - A symmetrical deforming cutaneous sporotrichosis with verrucous lesions on both hands and of long clinical duration is reported. The difficulties in making an etiological diagnosis are considered. PMID- 1406789 TI - Candidaemia: a 10-year study in an Indian teaching hospital. AB - Retrospective evaluation of candidaemia patients was performed in an Indian teaching hospital over a 10-year period. The incidence of patients with candidaemia increased eleven-fold in the second half of the study period (55 patients) compared with the first half (5 patients). Haematological malignancies (11 patients), neonatal septicaemia (9), cardiac abnormalities and cardiac surgery (9) were the commonest underlying diseases in these patients. Candida albicans (50%), C. guilliermondii (17%), C. tropicalis (15%) and C. parapsilosis (8%) were the most common fungal pathogens isolated from blood culture. Therapy with two or more antibiotics (92%), corticosteroid administration (25%), intravascular catheter use for over 24 h (78%) and neutropenia (48%) were the accountable predisposing factors. Prolonged hospitalization (mean average 22.2 days as compared with 11.2 days in other patients) was an added risk factor in these patients. PMID- 1406790 TI - Susceptibility to ketoconazole of Candida albicans strains from sequentially followed HIV-1 patients with recurrent oral candidosis. AB - The MIC values of the antifungal drug ketoconazole were evaluated on 66 Candida albicans strains. These strains were isolated from 26 HIV-1 infected patients with oral recurrent candidosis. Each episode of oral candidosis observed in these patients was orally treated with ketoconazole (200 mg/day) until the clinical disappearance of the lesions. The most frequent MIC values were 20 micrograms/ml and 10 micrograms/ml, observed in 37 and 19 isolates respectively. Only strains from five patients showed changes in their susceptibility to ketoconazole. This fact could indicate that a different strain causes the subsequent reappearance of the oral lesions, rather than the drug selecting resistant fungal strains. Our results stress the role of host characteristics in the occurrence of candidal infections, pointing to the progressing failure of the immunological response as the most important factor responsible for the recurrence of oral candidosis during HIV-1 infection. PMID- 1406791 TI - Virulence of Candida albicans mutants. AB - Mutant strains of the fungal pathogen Candida albicans blocked in pyrimidine transport and salvage metabolism were tested for virulence in various animal models. The growth rate, germination and proteolytic enzyme production did not correlate with the virulence of the strains. However, a defect in the uridine transport system significantly decreased virulence in murine candidosis, although it had no effect in vaginal candidosis or in a Candida cyst model. It remains unclear whether this is due to the differing host defence mechanisms involved in systemic and superficial mycoses, or to the different requirements of the fungal systems for adherence and tissue invasion in the two types of infection. PMID- 1406792 TI - The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. The HIV Infection in Newborns French Collaborative Study Group. AB - BACKGROUND: Early diagnosis of human immunodeficiency virus (HIV) infection in infants born to infected mothers is important for the infants' medical care, but the presence of maternal antibodies makes serologic tests uninformative. METHODS: In a cohort study of 181 infants born to HIV-infected mothers, we assessed the diagnostic value of HIV viral culture and testing for the presence of p24 antigen. The infants were tested at birth, again during the first 3 months, then followed and tested at the age of at least 18 months. RESULTS: Of the 181 infants, 3 died of HIV infection and 37 were seropositive after the age of 18 months. Viral cultures at birth were positive in 19 of the 40 infected infants and in none of the uninfected infants, yielding a sensitivity of 48 percent (95 percent confidence interval, 32 to 63 percent) and a specificity of 100 percent (95 percent confidence interval, 97 to 100 percent). By the age of three months, 30 of the 40 infants (75 percent) had positive cultures; again, there were no false positive results among the infants who were tested a second time, of the 141 who remained uninfected. The sensitivity of testing for p24 antigen at birth was only 18 percent, with a specificity of 100 percent. The presence of p24 antigen at birth was associated with the development of early and severe HIV related disease (P less than 0.04). CONCLUSIONS: Viral culture at birth can correctly identify about half of newborns with HIV infection. The fact that this usually sensitive technique fails to identify about half the ultimately infected neonates suggests that vertical transmission of HIV may occur late in pregnancy or during delivery. PMID- 1406793 TI - Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. AB - BACKGROUND: The idiotypic determinants of the surface immunoglobulin of a B-cell lymphoma can serve as a clonal tumor-specific marker, which may have implications for immunotherapy. We sought to determine whether idiotype-specific immune responses against this autologous antigen could be induced in patients with B cell lymphoma. METHODS: Nine patients were selected who had minimal residual disease or a complete remission after chemotherapy. Each received a series of subcutaneous injections of the immunoglobulin derived from his or her tumor cells (immunoglobulin-idiotype protein), which had been conjugated to a protein carrier and mixed with an immunologic adjuvant. RESULTS: In seven of the nine patients the injections induced sustained idiotype-specific immunologic responses of the humoral type (two patients), the cell-mediated type (four patients), or both (one patient). The use of an adjuvant was essential for these immune responses. The induced antibodies bound specifically to autologous immunoglobulin idiotype, inhibited the binding of murine monoclonal antiidiotype antibodies, and bound autologous tumor cells. Cell-mediated responses were demonstrated by the specific proliferation of immune peripheral-blood mononuclear cells to the soluble immunoglobulin-idiotype protein in vitro. The tumors of both of the patients with measurable disease regressed completely. Toxicity associated with the vaccine was minimal and consisted only of mild reactions at the site of intramuscular injection. CONCLUSIONS: These results demonstrate that autologous immunoglobulin idiotype can be formulated into an immunogenic, tumor-specific antigen in humans with B-cell lymphoma, and they provide the background for large-scale trials of active specific immunotherapy of this disease. PMID- 1406794 TI - Brief report: the molecular basis of steroid 5 alpha-reductase deficiency in a large Dominican kindred. PMID- 1406795 TI - The relation between experience and outcome in heart transplantation. AB - BACKGROUND: Current policies related to organ transplantation in the United States are designed to ensure that centers and physicians with experience in transplantation perform these procedures. It is essential to confirm the validity of such policies, since they may limit access to transplantation services. METHODS: To determine the relation between experience with heart transplantation and mortality after the procedure, we merged data from the registry of the International Society for Heart and Lung Transplantation with data from a survey that provided additional information about patients and transplantation centers. Our study included 1123 patients who received a heart transplant at one of 56 hospitals in the United States from 1984 through 1986. We used univariate and bivariate techniques, as well as logistic regression, to analyze our data. RESULTS: We observed an institutional learning curve for heart transplantation. Patients who received one of a center's first five transplants had higher mortality rates than patients who received a subsequent transplant (20 percent vs. 12 percent; P = 0.002; relative risk = 2.2; 95 percent confidence interval, 1.6 to 3.4). In addition, we found a correlation between the training of key personnel on the transplantation team and mortality at new transplantation centers. For example, new centers staffed by cardiologists with previous training in heart transplantation had lower mortality rates among heart-transplant recipients than centers without experienced cardiologists (7 percent vs. 16 percent; P = 0.001; relative risk = 2.7; 95 percent confidence interval, 1.3 to 5.9). By contrast, the previous training of the surgeons who performed transplantations was not related to the mortality rate associated with the procedure. CONCLUSIONS: Experience with heart transplantation is associated with a better outcome for patients after that procedure. Opportunities exist to refine transplantation policies on the basis of the experience of a center and its transplantation team and to develop similar policies for other forms of organ transplantation. PMID- 1406796 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 42-1992. A 59-year-old woman with severe, progressive dyspnea. PMID- 1406797 TI - Therapeutic clonotypic vaccines. PMID- 1406798 TI - Do medical journals suppress information? PMID- 1406799 TI - "Futility" as a criterion in limiting treatment. PMID- 1406800 TI - "Futility" as a criterion in limiting treatment. PMID- 1406801 TI - "Futility" as a criterion in limiting treatment. PMID- 1406802 TI - "Futility" as a criterion in limiting treatment. PMID- 1406803 TI - "Futility" as a criterion in limiting treatment. PMID- 1406804 TI - "Futility" as a criterion in limiting treatment. PMID- 1406805 TI - Clinical problem-solving: risky business. PMID- 1406806 TI - Clinical problem-solving: risky business. PMID- 1406807 TI - Clinical problem-solving: risky business. PMID- 1406808 TI - Clinical problem-solving: risky business. PMID- 1406809 TI - Infant mortality among blacks and whites. PMID- 1406810 TI - Infant mortality among blacks and whites. PMID- 1406811 TI - Infant mortality among blacks and whites. PMID- 1406812 TI - Global aphasia without hemiplegia. PMID- 1406813 TI - Prognosis in cystic fibrosis. PMID- 1406814 TI - The American health care system: private insurance. PMID- 1406815 TI - The American health care system: private insurance. PMID- 1406816 TI - Proposed definitions for in utero versus intrapartum transmission of HIV-1. PMID- 1406817 TI - A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group. AB - BACKGROUND: In Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease. METHODS: Of 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living. RESULTS: At the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P < 0.001). There were no differences between the groups in their global-rating scores. The tacrine group had a significantly smaller decline in the activities of daily living. The results of the Mini-Mental State Examination favored tacrine, but the differences were small and not statistically significant (a score of 16.0 with tacrine vs. 15.3 with placebo; P = 0.08). Gastrointestinal symptoms, elevation of aminotransferase levels, and headache were the most frequent side effects; all could be reversed by reducing the dose or discontinuing treatment. CONCLUSIONS: In this short-term study in patients with Alzheimer's disease who were selected for apparent responsiveness to tacrine, treatment with tacrine resulted in a statistically significant reduction in the decline of cognitive function, although this reduction was not large enough to be detected by the study physicians' global assessments of the patients. PMID- 1406818 TI - Cardiac structure and function in children with human immunodeficiency virus infection treated with zidovudine. AB - BACKGROUND: Abnormalities of cardiac structure and function are common in children infected with the human immunodeficiency virus (HIV). It is unclear, however, whether these abnormalities are attributable to the disease itself, associated infections, or possible cardiotoxic effects of the most commonly used treatment, zidovudine. METHODS: We performed echocardiography in 24 children with symptomatic HIV infection immediately before they started zidovudine therapy and a mean of 1.32 years after therapy began. Sixteen of these children were also studied a mean of 1.26 years before starting zidovudine treatment. Comparison groups included 27 age-matched children with symptomatic HIV infection who had not received zidovudine and 191 normal children. RESULTS: As compared with the normal children, the children treated with zidovudine had progressive left ventricular dilatation and an increase in ventricular-wall stress at end-systole (a measure of ventricular afterload); dilatation and stress were significantly elevated both before and during zidovudine treatment. The ratio of ventricular thickness to internal dimension was below normal before zidovudine treatment began (P < 0.001). After treatment with zidovudine, however, overall left ventricular mass was increased (P = 0.02), as was peak wall stress (a stimulus to ventricular hypertrophy) (P = 0.01). Ventricular contractility remained normal, but fractional shortening of the left ventricle was decreased (P = 0.004). No statistically significant differences were detected at follow-up in any of these measurements between HIV-infected children treated with zidovudine and those not so treated. CONCLUSIONS: Progressive left ventricular dilatation occurred in children with symptomatic HIV infection. Compensatory hypertrophy also occurred but was inadequate to maintain peak systolic wall stress within the normal range. The progressive elevation of ventricular afterload due to dilatation resulted in depressed ventricular performance, but intrinsic ventricular contractility remained normal. Zidovudine did not appear to worsen or ameliorate these cardiac changes. PMID- 1406819 TI - Brief report: idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells and airways disease. PMID- 1406820 TI - The use of molecular methods in infectious diseases. PMID- 1406821 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43--1992. A 70-year-old man with progressive muscle weakness and agitated depression. PMID- 1406822 TI - Exposure to lead in childhood. The importance of prevention. PMID- 1406823 TI - Let's make a deal. Negotiating a settlement between physicians and society. PMID- 1406824 TI - Redundant publication? PMID- 1406825 TI - Prognostic factors in breast cancer. PMID- 1406826 TI - Prognostic factors in breast cancer. PMID- 1406827 TI - Prognostic factors in breast cancer. PMID- 1406828 TI - Rectal doxepin and carbamazepine therapy in patients with cancer. PMID- 1406829 TI - Magnetic resonance versus conventional angiography in peripheral arterial occlusive disease. PMID- 1406830 TI - Magnetic resonance versus conventional angiography in peripheral arterial occlusive disease. PMID- 1406831 TI - Ophthalmopathy after treatment for Graves' hyperthyroidism. PMID- 1406832 TI - Ophthalmopathy after treatment for Graves' hyperthyroidism. PMID- 1406833 TI - Snake-venom and insect-venom extractors: an unproved therapy. PMID- 1406834 TI - Predictors of long-term outcome after percutaneous balloon mitral valvuloplasty. AB - BACKGROUND: Percutaneous balloon mitral valvuloplasty is known to produce short term hemodynamic and symptomatic improvement in many patients with mitral stenosis. Comprehensive assessment of the clinical usefulness of balloon valvuloplasty requires evaluation of patients' long-term outcomes. METHODS: We performed balloon mitral valvuloplasty in 146 patients between October 1, 1985, and October 1, 1991. Base-line demographic, clinical, echocardiographic, and hemodynamic variables were evaluated in order to identify predictors of long-term event-free survival. RESULTS: Balloon mitral valvuloplasty was completed successfully in 136 (93 percent) of the patients in whom the procedure was attempted; it resulted in an increase in the mean (+/- SD) mitral-valve area from 1.0 +/- 0.4 to 2.1 +/- 0.9 cm2 and a decrease in the mean transmitral pressure gradient from 14 +/- 5 to 6 +/- 3 mm Hg (P < 0.001 for both comparisons). The estimated overall five-year survival rate was 76 +/- 5 percent, and the estimated five-year event-free survival rate (the percentage of patients without mitral valve replacement, repeat valvuloplasty, or death from cardiac causes) was 51 +/- 6 percent. According to multivariate Cox proportional-hazards analysis, the independent predictors of longer event-free survival were a lower mitral-valve echocardiographic score (a measure of mitral-valve deformity; range, 0 for a normal valve to 16 for a seriously deformed valve; P < 0.001), lower left ventricular end-diastolic pressure (P = 0.001), and a lower New York Heart Association (NYHA) functional class (P = 0.04). Patients with no risk factors for early restenosis or only one risk factor (echocardiographic score > 8, left ventricular end-diastolic pressure > 10 mm Hg, or NYHA functional class IV) had a predicted five-year event-free survival rate of 60 to 84 percent, whereas patients with two or three risk factors had a predicted five-year event-free survival rate of only 13 to 41 percent. CONCLUSIONS: Balloon mitral valvuloplasty as a treatment for selected patients with mitral stenosis has good long-term results. The long-term outcome after this procedure can be predicted on the basis of patients' base-line characteristics. PMID- 1406835 TI - Interferon alfa combined with cytotoxic chemotherapy for patients with non Hodgkin's lymphoma. AB - BACKGROUND: Interferon alfa has been found to be effective as an antitumor agent (with a response rate of 30 percent) in patients with low-grade non-Hodgkin's lymphoma, but its effectiveness in those with intermediate-grade non-Hodgkin's lymphoma has been less adequately tested. In a prospective randomized study we evaluated the effectiveness of adding interferon alfa to cytotoxic chemotherapy in patients with clinically aggressive, low-grade non-Hodgkin's lymphoma and certain histologic variants of intermediate-grade non-Hodgkin's lymphoma, not including diffuse histiocytic lymphoma. METHODS: The patients were randomly assigned to a regimen of cyclophosphamide, vincristine, prednisone, and doxorubicin or to this regimen combined with recombinant interferon alfa. Treatment was administered every four weeks, for 8 to 10 cycles. RESULTS: The two regimens produced comparable objective responses, but the regimen including interferon had a greater effect in prolonging the time to treatment failure (P < 0.001) and the duration of complete response (P = 0.03). Interferon alfa also had a greater effect on overall survival (P = 0.014) when the results were adjusted for important covariates. CONCLUSIONS: Interferon alfa, when added to a four-drug doxorubicin-based chemotherapy regimen, is an effective antitumor agent in patients with clinically aggressive low-grade or intermediate-grade non-Hodgkin's lymphoma. PMID- 1406836 TI - Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935. AB - BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up. PMID- 1406837 TI - Brief report: melatonin-related hypogonadotropic hypogonadism. PMID- 1406838 TI - HIV disease and the endocrine system. PMID- 1406839 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 44-1992. A 60-year-old man with HIV infection, persistent diarrhea, and intractable respiratory failure. PMID- 1406840 TI - Melatonin--the hormone of darkness. PMID- 1406841 TI - Adolescent overweight may be tempting fate. PMID- 1406842 TI - Care of the hopelessly ill. Proposed clinical criteria for physician-assisted suicide. PMID- 1406843 TI - Disclosure of AIDS in celebrities. PMID- 1406844 TI - Hand-washing agents and nosocomial infections. PMID- 1406845 TI - Hand-washing agents and nosocomial infections. PMID- 1406846 TI - Hand-washing agents and nosocomial infections. PMID- 1406847 TI - New OSHA regulations for physicians' offices. PMID- 1406848 TI - Use of psychoactive drugs in nursing homes. PMID- 1406849 TI - Use of psychoactive drugs in nursing homes. PMID- 1406850 TI - Effect of cocaine use on the fetus. PMID- 1406851 TI - Effect of cocaine use on the fetus. PMID- 1406852 TI - Impairment of renal function with increasing blood lead concentrations. PMID- 1406853 TI - Clinical problem-solving: failure to resolve a diagnostic inconsistency. PMID- 1406854 TI - Clinical problem-solving: failure to resolve a diagnostic inconsistency. PMID- 1406855 TI - Cat-scratch salpingitis. PMID- 1406856 TI - Fludarabine and acute tumor lysis in chronic lymphocytic leukemia. PMID- 1406857 TI - Wartenberg wheel-and-flair reaction--a prickly problem. PMID- 1406858 TI - The psychological consequences of predictive testing for Huntington's disease. Canadian Collaborative Study of Predictive Testing. AB - BACKGROUND: Advances in molecular genetics have led to the development of tests that can predict the risk of inheriting the genes for several adult-onset diseases. However, the psychological consequences of such testing are not well understood. METHODS: The 135 participants in the Canadian program of genetic testing to predict the risk of Huntington's disease were followed prospectively in three groups according to their test results: the increased-risk group (37 participants), the decreased-risk group (58 participants), and the group with no change in risk (the no-change group) (40 participants). All the participants received counseling before and after testing. Standard measures of psychological distress (the General Severity Index of the Symptom Check List 90-R), depression (the Beck Depression Inventory), and well-being (the General Well-Being Scale) were administered before genetic testing and again at intervals of 7 to 10 days, 6 months, and 12 months after the participants received their test results. RESULTS: At each follow-up assessment, the decreased-risk group had lower scores for distress than before testing (P < 0.001). The increased-risk group showed no significant change from base line on any follow-up measure, but over the year of study there were small linear declines (P < 0.023) for distress and depression. The no-change group had scores lower than at base line on the index of general well-being at each follow-up (P < or = 0.045). At the 12-month follow-up, both the increased-risk group and the decreased-risk group had lower scores for depression and higher scores for well-being than the no-change group (P < or = 0.049). CONCLUSIONS: Predictive testing for Huntington's disease has potential benefits for the psychological health of persons who receive results that indicate either an increase or a decrease in the risk of inheriting the gene for the disease. PMID- 1406859 TI - Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators. AB - BACKGROUND: Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk. METHODS: We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death. RESULTS: Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history. CONCLUSIONS: Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age. PMID- 1406860 TI - Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. AB - BACKGROUND: Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment. METHODS: We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group). RESULTS: The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001). CONCLUSIONS: In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration. PMID- 1406861 TI - Genetic testing for Huntington's disease--a family issue. PMID- 1406862 TI - Randomized trials of warfarin for atrial fibrillation. PMID- 1406863 TI - Combination therapy in NIDDM. PMID- 1406864 TI - Aspirin in ischemic heart disease. PMID- 1406865 TI - Aspirin in ischemic heart disease. PMID- 1406867 TI - Thromboxane and prostacyclin metabolites in pulmonary hypertension. PMID- 1406866 TI - Aspirin in ischemic heart disease. PMID- 1406868 TI - Diagnosis of colonic tumors by hydrocolonic sonography. PMID- 1406869 TI - Diagnosis of colonic tumors by hydrocolonic sonography. PMID- 1406870 TI - AIDS and absolutism. PMID- 1406871 TI - AIDS and absolutism. PMID- 1406872 TI - AIDS and absolutism. PMID- 1406873 TI - Avoiding puncture wounds in the operating room. PMID- 1406874 TI - Primaquine-induced methemoglobinemia during treatment of Pneumocystis carinii pneumonia. PMID- 1406875 TI - Underinsurance in America. PMID- 1406876 TI - Underinsurance in America. PMID- 1406877 TI - Blotter's blister. PMID- 1406878 TI - The American health care system. Medicare. PMID- 1406879 TI - Effect of iron chelation therapy on recovery from deep coma in children with cerebral malaria. AB - BACKGROUND: Cerebral malaria is a severe complication of Plasmodium falciparum infection in children, with a mortality rate of 15 to 50 percent despite antimalarial therapy. METHODS: To determine whether combining iron chelation with quinine therapy speeds the recovery of consciousness, we conducted a randomized, double-blind, placebo-controlled trial of the iron chelator deferoxamine in 83 Zambian children with cerebral malaria. To be enrolled, patients had to be less than six years old, have P. falciparum parasitemia, have normal cerebrospinal fluid without evidence of bacterial infection, and be in a coma from which they could not be aroused. Deferoxamine (100 mg per kilogram of body weight per day, infused intravenously for 72 hours) or placebo was added to standard therapy with quinine and sulfadoxine-pyrimethamine. The time to the recovery of full consciousness, time to parasite clearance, and mortality were examined with Cox proportional-hazards regression analysis. RESULTS: The rate of recovery of full consciousness among the 42 patients given deferoxamine was 1.3 times that among the 41 given placebo (95 percent confidence interval, 0.7 to 2.3); the median time to recovery was 20.2 hours in the deferoxamine group and 43.1 hours in the placebo group (P = 0.38). Among 50 patients with deep coma, the rate of recovery of full consciousness was increased 2.2-fold with deferoxamine (95 percent confidence interval, 1.1 to 4.7), decreasing the median recovery time from 68.2 to 24.1 hours (P = 0.03). Among 69 patients for whom data on parasite clearance were available, the rate of clearance with deferoxamine was 2.0 times that with placebo (95 percent confidence interval, 1.2 to 3.6). Among all 83 patients, mortality was 17 percent in the deferoxamine group and 22 percent in the placebo group (P = 0.52). CONCLUSIONS: Iron chelation therapy may hasten the clearance of parasitemia and enhance recovery from deep coma in cerebral malaria. PMID- 1406880 TI - Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis. AB - BACKGROUND: In most countries, heparin is used in the initial treatment of patients with deep-vein thrombosis. Well-designed studies establishing the efficacy of heparin therapy are lacking, however. Treatment with acenocoumarol alone, according to the hypothesis that high dosages of oral anticoagulants obviate the need for heparin, is considered an effective alternative in some countries. METHODS: In a randomized, double-blind study we compared the efficacy and safety of continuous intravenous heparin plus acenocoumarol with the efficacy and safety of acenocoumarol alone in the initial treatment of outpatients with proximal-vein thrombosis. The principal study end point was a confirmed symptomatic extension or recurrence of venous thromboembolism during six months of follow-up. In addition, we assessed asymptomatic extension or pulmonary embolism by repeating venography and lung scanning after the first week of treatment. The incidence of major bleeding was determined during three months of follow-up. RESULTS: The study was terminated early by the Data Safety and Monitoring Committee because of an excess of symptomatic events in the group that received acenocoumarol alone (in 12 of 60 patients [20 percent], as compared with 4 of 60 patients [6.7 percent] in the combined-therapy group by intention-to treat analysis; P = 0.058). Asymptomatic extension of venous thrombosis was observed in 39.6 percent of the patients in the acenocoumarol group and in 8.2 percent of patients treated with heparin plus acenocoumarol (P < 0.001). Major bleeding complications were infrequent and comparable in the two groups. CONCLUSIONS: Patients with proximal-vein thrombosis require initial treatment with full-dose heparin, which can safely be combined with acenocoumarol therapy. PMID- 1406881 TI - Consequences of physicians' ownership of health care facilities--joint ventures in radiation therapy. AB - BACKGROUND: Physicians are increasingly the owners of health care facilities to which they refer patients for services but at which they do not practice. We studied such ownership arrangements, known as "joint ventures," in the field of radiation therapy, examining their effects on access, use of services, costs, and quality. METHODS: Because 44 percent of free-standing facilities providing radiation therapy in Florida in 1989 were joint ventures, as compared with 7 percent elsewhere (95 percent confidence interval, 3 to 10 percent), we compared data for Florida with comparable data for the remainder of the United States. We also compared radiation-therapy facilities in Florida that were established as joint ventures with those that were not. Since most data were derived from entire populations rather than from samples, any differences found were of necessity statistically significant. RESULTS: No joint-venture facilities providing radiation therapy were located in inner-city neighborhoods or rural areas, but 11 percent of other free-standing facilities and hospital-based facilities were located in such areas. Among free-standing facilities, joint ventures received 39 percent of their revenues from patients with well-paying insurance coverage, as compared with 31 percent for facilities that were not joint ventures (P < 0.01). The frequency and costs of radiation-therapy treatments at free-standing centers were 40 to 60 percent higher in Florida than in the rest of the United States; there was no below-average use of radiation therapy at hospitals or higher cancer rates that explained the higher rates of use or higher costs in Florida. Radiation physicists at joint-venture facilities (the principal personnel involved in quality control other than physicians) spent 18 percent less time with each patient over the course of treatment than did their counterparts at free-standing facilities that were not joint ventures (P < 0.05). Mortality among patients with cancer in Florida was not lower than the U.S. average, even though joint ventures are much more common in that state. CONCLUSIONS: Joint ventures in radiation therapy appear to have adverse effects on patients' access to care. They also appear to increase the use of services and costs substantially. Some indicators show that joint ventures cause either no improvement in quality or a decline. Our results add to the evidence indicating that physicians' self referral generally has negative consequences. We recommend legislation to ban ownership of joint ventures by referring physicians. Such legislation needs to be carefully designed in order to achieve its objectives and forestall new, financially abusive arrangements. PMID- 1406883 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 46-1992. A 48-year-old woman with a narrowed trachea. PMID- 1406882 TI - Increased costs and rates of use in the California workers' compensation system as a result of self-referral by physicians. AB - BACKGROUND: There is widespread concern that ownership by physicians of testing or treatment facilities to which they refer patients leads to overuse of such facilities. We determined the patterns of use of three services--physical therapy, psychiatric evaluation, and magnetic resonance imaging (MRI)--among physicians treating patients whose care was covered under workers' compensation. We then compared the rates of use among physicians who referred patients to facilities of which they were owners (self-referral group) with the rates among physicians who referred patients to independent facilities (independent-referral group). METHODS: We used a large data base to analyze claims under workers' compensation in California from October 1, 1990, through June 30, 1991, to determine the frequency and cost of these three selected services and determined whether the referring physicians were practicing self-referral or independent referral. We evaluated the cost per case for all three services, measured the frequency with which physical therapy was initiated, and evaluated the medical appropriateness of MRI. RESULTS: We found that physical therapy was initiated 2.3 times more often by the physicians in the self-referral group (68 percent) than by those in the independent-referral group (30 percent; P < 0.01). The mean cost per case for physical therapy was significantly lower in the self-referral group ($404 +/- 102) than in the independent-referral group ($440 +/- 167; P < 0.01). The mean cost of psychiatric evaluation services was significantly higher in the self-referral group than in the independent-referral group (psychometric testing, $1,165 +/- 728 vs. $870 +/- 482; P < 0.01, psychiatric evaluation reports, $2,056 +/- 1,063 vs. $1,680 +/- 578; P < 0.01). The total cost per case of psychiatric evaluation services was 26.3 percent higher in the self-referral group ($3,222 +/ 1,451) than in the independent-referral group ($2,550 +/- 742; P < 0.01). Of all the MRI scans requested by the self-referring physicians, 38 percent were found to be medically inappropriate, as compared with 28 percent of those requested by physicians in the independent-referral group (P < 0.05). There was no significant difference in the cost per case between the two groups. CONCLUSIONS: This study demonstrates that self-referral increases the cost of medical care covered by workers' compensation for each of the three types of service studied. PMID- 1406884 TI - Bark, weeds, and iron chelators--drugs for malaria. PMID- 1406885 TI - "Self-referral"--what's at stake? PMID- 1406886 TI - Comprehensive health care reform and managed competition. PMID- 1406887 TI - Detection of HIV provirus by in situ polymerase chain reaction. PMID- 1406888 TI - Detection of HIV provirus by in situ polymerase chain reaction. PMID- 1406889 TI - The risk of stroke after thrombolytic therapy. PMID- 1406890 TI - The risk of stroke after thrombolytic therapy. PMID- 1406891 TI - Gatekeeping. PMID- 1406892 TI - Gatekeeping. PMID- 1406893 TI - Gatekeeping. PMID- 1406894 TI - Gatekeeping. PMID- 1406895 TI - Gatekeeping. PMID- 1406896 TI - Trombonist's torment. PMID- 1406897 TI - Mycetismus 'mushroom poisoning'. PMID- 1406898 TI - In vitro activity of cloconazole, sulconazole, butoconazole, isoconazole, fenticonazole, and five other antifungal agents against clinical isolates of Candida albicans and Candida spp. AB - The in vitro activity of several new imidazoles, cloconazole, sulconazole, butoconazole, isoconazole and fenticonazole, were compared with those of amphothericin B, flucytosine, and three azoles: econazole, miconazole and ketoconazole against isolates of pathogenic Candida. A total of 186 clinical isolates of 10 species of the genus Candida and two culture collection strains were tested by an agar-dilution technique. Isoconazole was the most active azole, followed by butoconazole sulconazole. Differences between some of the species in their susceptibility to the antifungal agents were noted. Sulconazole and cloconazole had the highest activity in vitro against 106 isolates of C. albicans. Butoconazole and isoconazole were also very active against isolates of C. albicans, and were the most active azole compounds against 80 isolates of Candida spp. PMID- 1406899 TI - Use of a colorimetric system to detect enzymes expressed by germinating conidia of entomopathogenic fungi. AB - An apiZYM system, with 19 substrates, was used to detect enzymes expressed by germinating conidia of Nomuraea rileyi (5 isolates), Nomuraea atypicola, Nomuraea anemonoides, Beauveria bassiana and Metarhizium anisopliae. Similar enzyme profiles were obtained for two of the N. rileyi isolates (Mississippi, Ecuador) regardless of whether culture medium (Sabouraud-maltose-yeast) or cuticle (from larvae of Trichoplusia ni, Heliothis zea or Heliothis virescens) were used as substrates. Centroid-clustering analysis revealed three distinct enzyme profiles. PMID- 1406900 TI - Mushroom poisoning by Chlorophyllum molybdites in the Midwest United States. Cases and a review of the syndrome. AB - The paper describes two incidents of poisoning by the mushroom Chlorophyllum molybdites and reviews the literature covering this organism, a common agent of mushroom poisoning in many countries and the most common cause of mushroom poisoning in North America. Both poisoning incidents occurred in adults and were associated with severe gastrointestinal symptoms including profuse diarrhea, vomiting and intestinal pain. In each case, hospitalization was required. An unusual aspect of one case was the development of signs and symptoms suggestive of muscarine poisoning. The review includes a description of the mushroom, the geographic distribution of cases, the signs and symptoms of poisoning and its treatment, the toxic principles, particularly susceptible populations, and the variations in response associated with cooking C. molybdites and with individual idiosyncrasies. For identification of C. molybdites, the reader is alerted to the inappropriateness of some books, including many written in Europe, and is warned of the occasional finding of sterile mushrooms that lack its characteristic green basidiospores. Spores, as allergens, are discussed and simple rules are given for eaters of wild mushrooms. PMID- 1406901 TI - Pulmonary paracoccidioidomycosis in immunized mice. AB - Paracoccidioidomycosis was induced in immunized (IM) and non-immunized (NI) mice. The histopathology, the number of fungi in the lungs, the cellular (footpad test- FPT and macrophage inhibition factor assay--MIF) and humoral (immunodiffusion test) immune response were investigated serially post-infection. In the IM mice, at days 1 and 3, there was intense and predominant macrophagic-lymphocytic alveolitis with loose granulomatous reaction; at day 30, inflammation was mild. In the NI group, up to day 3, the lesions were focal; later there was formation of extensive epithelioid granuloma. The number of fungi in IM mice were always smaller than those of NI group. Immunization alone induced positive FPT and MIF indices with low titer of antibody. After infection, there was a significant decrease of the FPT indices in the IM group, which we interpreted as desensitization due to trapping of sensitized lymphocytes in the lungs. In conclusion, (1) The lesional pattern of pulmonary paracoccidioidomycosis in IM mice was similar to that of a hypersensitivity pneumonitis. This reaction was probably effective in reducing the extension of the infection and decrease the number of fungi. (2) In this model, pulmonary resistance against P. brasiliensis seems to be related to local and systemic delayed-type hypersensitivity reaction. PMID- 1406902 TI - Evaluation of the Pro-Lab ID ring system for the identification of medically important yeasts. AB - We evaluated 151 coded isolates of medically important yeast species belonging to the genera Candida, Cryptococcus, Geotrichum, Rhodoturula, Saccharomyces and Torulopsis using the newly developed rapid Pro-Lab Identification Ring, PL 960 system (PLID-Ring). All isolates were concurrently identified by the API 20C and conventional procedures comprising macro- and micromorphology, assimilation and fermentation of various carbon and nitrogen compounds. The PLID-Ring system identified isolates of Candida albicans, C. kefyr, C. krusei, C. lusitaniae, C. parapsilosis, Rhodotorula rubra, and Torulopsis glabrata with 100% accuracy in 24 h. This system identified C guilliermondii and S. cerevisiae isolates with an accuracy of 90% and 86%, respectively, while those belonging to Cr. neoformans, T. candida (= C. famata), C. rugosa and C. tropicalis were identified with 38.4%, 50%, 12.5% and 50% accuracy, respectively. Three isolates of Cr. laurentii were not identified by the PLID-Ring system. The overall accuracy of the PLID-Ring system was 81.45% (123 of 151 isolates). However, the system does not include species such as Cr. laurentii in its data base. When these three Cr. laurentii isolates were excluded from the evaluation, the accuracy of the PLID-Ring system increased from 81.45% to 83.1%. PMID- 1406903 TI - Effect of environmental factors on Fonsecaea pedrosoi morphogenesis with emphasis on sclerotic cells induced by propranolol. AB - The influence of growth conditions, as well as of propranolol on Fonsecaea pedrosoi morphogenesis was established using the chemically defined media of Czapeck-Dox (CD) and Butterfield (BF). Mycelial growth of F. pedrosoi in both media was obtained at room temperature (25 degrees C) for 14 days, without shaking, whereas conidia formed at 37 degrees C, for 4 days, in shaken cultures and could be isolated free from the mycelium by filtration in gauze. At low pH (2.5-3.0), there appeared sclerotic cells attached to normal hyphae. When propranolol ws added to the CD medium moniliform hyphae were observed, whereas this drug in the BF medium induced formation of sclerotic cells. Ultrastructural examination revealed that the propranolol-induced sclerotic cells were very similar to those observed in infected tissues. PMID- 1406904 TI - Forty four years of dermatophytes in a Chicago clinic (1944-1988). AB - Data are presented on 39,270 cultures taken over a 44 year span (1944-1988) at the University of Chicago's Dermatology Clinic. In the mid 1940's Microsporum audouinii accounted for 60-80% of isolates. It gradually decreased over the next two decades and disappeared altogether in the 1970's. Trichophyton rubrum, rare in the 1940's accounted for over 60% of isolates in the mid-1960's only to be overtaken by T. tonsurans. This species, not isolated till the mid 1950's, became and remains the dominant dermatophyte at the present time. Both T. mentagrophytes and Epidermophyton floccosum increased in the 1970's and decreased later. Unusual circumstances resulted in clusters of T. verrucosum, T. terrestre, and T. schoenleinii isolates. Infections were associated with rural dairy workers, zoo handlers and immigrant families respectively. M. canis and M. gypseum were steady at a low rate throughout the entire period. Rare isolates included M. cookei, M. persicolor, M. racemosum, T. simii, T. soudanense, T. violaceum, and the soil keratinophile, Aphanoascus fulvescens. PMID- 1406905 TI - Mycotic keratitis caused by Curvularia brachyspora (Boedjin). A report of the first case. AB - Curvularia brachyspora has been identified for the first time as a cause of mycotic keratitis. Mycotic infections of the eye have assumed increasing importance in ophthalmology, resulting in a need for fungal identification and early specific treatment for the successful management of cases. A case of mycotic keratitis caused by C. brachyspora is described against the background of other Curvularia species causing mycoses. PMID- 1406906 TI - Phase II clinical trials of buprenorphine: detoxification and induction onto naltrexone. PMID- 1406907 TI - Behavioral pharmacology of buprenorphine: issues relevant to its potential in treating drug abuse. PMID- 1406908 TI - Assessment of buprenorphine in a drug discrimination procedure in humans. AB - These studies indicate that buprenorphine shares stimulus effects with other opioid drugs and that in overall profile of effects buprenorphine is more similar to hydromorphone than are the other opioid mixed agonist-antagonists tested pentazocine, butorphanol, and nalbuphine. This characterization is supported by the behavioral drug discrimination results and by the subjective effect self report results. In the drug discrimination assessments buprenorphine showed a pattern of generalization that was different from that of the other opioid-mixed agonist-antagonists. It did not generalize completely to either pentazocine or butorphanol, but it did generalize to hydromorphone in two studies and partially in a third. Both nalbuphine and pentazocine showed at least partial generalization to butorphanol, but buprenorphine did not. Butorphanol showed little generalization to hydromorphone except in the two-choice hydromorphone vs. saline discrimination in which all the tested mixed agonist-antagonists generalized to hydromorphone. The subjective effect self-report data also revealed a pattern of response to buprenorphine that was different from that to the other mixed agonist-antagonists. In particular, buprenorphine's profile of acute subjective effects was similar to that of hydromorphone. There were dose related increases on various scales reflecting positive subjective effects, with little evidence of the dysphoric effects that are characteristic of high doses of the other mixed agonist-antagonists. These data are compatible with the view that buprenorphine is a partial agonist at the mu-receptor. Although they do not demonstrate the ceiling on magnitude of pharmacological effects that would be characteristic of a partial agonist, they do demonstrate that buprenorphine's profile of activity--both stimulus effects and subjective effects--is similar to that of the pure mu-agonist hydromorphone. PMID- 1406909 TI - Human laboratory studies of buprenorphine. PMID- 1406910 TI - Buprenorphine--background to its development as a treatment for opiate dependence. PMID- 1406911 TI - Primate studies of the behavioral pharmacology of buprenorphine. PMID- 1406912 TI - Saving on health. PMID- 1406914 TI - Blow struck against US pork-barrel. PMID- 1406913 TI - Rebuild research now. PMID- 1406915 TI - French court upholds use of animals, fines activists for theft of baboons. PMID- 1406916 TI - Confusion about form and function clouds launch of EC's Decade of the Brain. PMID- 1406917 TI - First meeting of commission gives Massey a boost in plotting viable future for NSF. PMID- 1406918 TI - User fees advance in Congress. PMID- 1406919 TI - New rules in Britain make it harder for older scientists to use animals. PMID- 1406920 TI - US rejects French request to reopen AIDS patent deal. PMID- 1406921 TI - Emphasis on research blamed for problems at US universities. PMID- 1406922 TI - NIH cDNA patent rejected; backers want to amend law. PMID- 1406923 TI - Alberts emphasizes education as nominee to head NAS. PMID- 1406924 TI - OST rows with tide in report on intellectual property. PMID- 1406925 TI - Genetic influence. PMID- 1406926 TI - Remedies for brain disorders. PMID- 1406927 TI - Alzheimer's disease. In search of the soluble. PMID- 1406928 TI - Retinoblastoma. For our eyes only. PMID- 1406929 TI - Signal transduction. Rac and Rho in tune. PMID- 1406930 TI - Rabies in wild dogs. PMID- 1406931 TI - Origin of rodents and guinea-pigs. PMID- 1406932 TI - Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. AB - The retinoblastoma gene, a prototypic tumour-suppressor gene, encodes a nuclear phosphoprotein (Rb). To understand better the role of Rb in development and in tumorigenesis, mice with an insertional mutation in exon 20 of the Rb-1 locus were generated. Homozygous mutants die before the 16th embryonic day with multiple defects. The haematopoietic system is abnormal; there is a significant increase in the number of immature nucleated erythrocytes. In the nervous system, ectopic mitoses and massive cell death are found, particularly in the hindbrain. All spinal ganglion cells die, but the neural retina is unaffected. Transfer of the human retinoblastoma (RB) mini-transgene into the mutant mice corrects the developmental defects. Thus, Rb is essential for normal mouse development. PMID- 1406934 TI - Predictable eye-head coordination during driving. AB - Large changes in the direction of gaze are made with a combination of fast saccadic eye movements and rather slower head movements. Since the first study on freely moving subjects, most authors have agreed that the head movement component of gaze is very variable, with a high 'volitional' component. But in some circumstances head and eye movements can be quite predictable, for example when a subject is asked to shift gaze as quickly as possible. Under these conditions, laboratory studies have shown that the eye and head motor-systems both receive gaze-change commands, although they execute them in rather different ways. Here I reconsider the way gaze direction is changed during free movement, but in the performance of a task where the subject is too busy to exert conscious control over head or eye movements. Using a new portable and inexpensive method for recording head and eye movements, I examine the oculomotor behaviour of car drivers, particularly during the large gaze changes made at road junctions. The results show that the pattern of eye and head movements is highly predictable, given only the sequence of gaze targets. PMID- 1406933 TI - Effects of an Rb mutation in the mouse. AB - The retinoblastoma gene is mutated in several types of human cancer and is the best characterized of the tumour-suppressor genes. A mouse strain has been constructed in which one allele of Rb is disrupted. These heterozygous animals are not predisposed to retinoblastoma, but some display pituitary tumours arising from cells in which the wild-type Rb allele is absent. Embryos homozygous for the mutation die between days 14 and 15 of gestation, exhibiting neuronal cell death and defective erythropoiesis. PMID- 1406935 TI - Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy. AB - X-linked recessive Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, a membrane cytoskeletal protein. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoprotein. The dystrophin-glycoprotein complex has been proposed to span the sarcolemma to provide a link between the subsarcolemmal cytoskeleton and the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a large reduction in all of the dystrophin-associated protein. We have investigated the possibility that a deficiency of a dystrophin-associated protein could be the cause of severe childhood autosomal recessive muscular dystrophy (SCARMD) with a DMD-like phenotype. Here we report the specific deficiency of the 50K dystrophin associated glycoprotein (M(r) 50,000) in sarcolemma of SCARMD patients. Therefore, the loss of this glycoprotein is a common denominator of the pathological process leading to muscle cell necrosis in two forms of muscular dystrophy, DMD and SCARMD. PMID- 1406936 TI - Isolation and quantification of soluble Alzheimer's beta-peptide from biological fluids. AB - Cerebral deposition of the beta-amyloid peptide (A beta) is an invariant feature of Alzheimer's disease. Since the original isolation and characterization of A beta (ref. 1) and the subsequent cloning of its precursor protein, no direct evidence for the actual production of discrete A beta has been reported. Here we investigate whether A beta is present in human biological fluids using antibodies specific for an epitope within A beta that spans the site of normal constitutive cleavage. These antibodies were used to construct a sandwich-type enzyme-linked immunosorbent assay that detects A beta in cerebrospinal fluid, plasma and conditioned medium of human mixed-brain cells grown in vitro (see also ref. 14). By affinity chromatography, we have purified and sequenced A beta and a novel A beta fragment from human cerebrospinal fluid and conditioned medium of human mixed-brain cell cultures. These findings demonstrate that A beta is produced and released both in vivo and in vitro. These observations offer new opportunities for developing diagnostic tests for Alzheimer's disease and therapeutic strategies aimed at reducing the cerebral deposition of A beta. PMID- 1406937 TI - Requirement for a functional Rb-1 gene in murine development. AB - Human retinoblastomas can occur both as hereditary and as sporadic cases. Knudson's proposal that they result from two mutational events, of which one is present in the germ line in hereditary cases, has been confirmed by more recent molecular analysis, which has shown both events to involve loss or mutational inactivation of the same gene, RB-1 (ref. 2). RB-1 heterozygosity also predisposes to osteosarcoma, and RB-1 allele losses are seen in sporadic lung, breast, prostate and bladder carcinomas. RB-1 is expressed in most, if not all, tissues and codes for a nuclear phosphoprotein which becomes hypophosphorylated in the G0 growth arrest state and in the G1 phase of the cell cycle. To gain a further insight into the role of RB-1 we and other groups have generated mice carrying an inactivated allele of the homologous gene, Rb-1 (ref. 10), by gene targeting. We report here that young heterozygous mice do not appear abnormal and do not develop retinoblastoma at a detectable frequency. However, homozygous mutant embryos fail to reach term and show a number of abnormalities in neural and haematopoietic development. Broadly similar results are reported by the other groups. PMID- 1406938 TI - Inefficient positive selection of T cells directed by haematopoietic cells. AB - Intrathymic differentiation of alpha beta TCR+ T cells depends on positive selection of CD4+CD8+ thymocytes by thymic major histocompatibility complex (MHC) molecules. Positive selection allows the maturation of only those T cells capable of restricted antigen recognition in the context of the hosts' MHC alleles. Studies of normal or T-cell receptor-transgenic mice engrafted with MHC-different bone marrow or thymuses support the conclusion that positive selection is directed by MHC molecules expressed on non-haematopoietic cells, presumably thymic epithelial cells. Here we, present contrary evidence that class I MHC molecules expressed by haematopoietic cell types direct positive selection of CD8+ T cells, though at a reduced rate compared with positive selection directed by thymic epithelial cells. The identity of cell types that direct positive selection bears directly on mechanistic models of the process, including the idea that thymic epithelial cell MHC molecules uniquely present specialized peptides that mediate positive selection, and the notion that thymic epithelial cells express unique differentiation-inducing cell surface molecules. PMID- 1406939 TI - The candidate oncoprotein Bcl-3 is an antagonist of p50/NF-kappa B-mediated inhibition. AB - The candidate oncogene bcl-3 was discovered as a translocation into the immunoglobulin alpha-locus in some cases of B-cell chronic lymphocytic leukaemias. The protein Bcl-3 contains seven so-called ankyrin repeats. Similar repeat motifs are found in a number of diverse regulatory proteins but the motifs of Bcl-3 are most closely related to those found in I kappa B proteins in which the ankyrin repeat domain is thought to be directly involved in inhibition of NF kappa B activity. No biological function has yet been described for Bcl-3, but it was noted recently that Bcl-3 interferes with DNA-binding of the p50 subunit of NF-kappa B in vitro. Here we demonstrate that Bcl-3 can aid kappa B site dependent transcription in vivo by counteracting the inhibitory effects of p50/NF kappa B homodimers. Bcl-3 may therefore aid activation of select NF-kappa B regulated genes, including those of the human immunodeficiency virus. PMID- 1406941 TI - Courts reject DNA fingerprinting, citing controversy after NAS report. PMID- 1406940 TI - Gene patents. PMID- 1406942 TI - A mess of red pottage. PMID- 1406943 TI - Malaria. Getting into the liver. PMID- 1406944 TI - Cancer genetics. Imprinting in leukaemia. PMID- 1406945 TI - Developmental biology. Big genes and little genes and deadlines for transcription. PMID- 1406946 TI - Human Genome Project: Mapping the way ahead. PMID- 1406947 TI - Actin in cell attachment. PMID- 1406948 TI - Allelic exclusion model questioned. PMID- 1406949 TI - Allelic exclusion model questioned. PMID- 1406950 TI - Continuum of overlapping clones spanning the entire human chromosome 21q. AB - A continuous array of overlapping clones covering the entire human chromosome 21q was constructed from human yeast artificial chromosome libraries using sequence tagged sites as landmarks specifically detected by polymerase chain reaction. The yeast artificial chromosome contiguous unit starts with pericentromeric and ends with subtelomeric loci of 21q. The resulting order of sequence-tagged sites is consistent with other physical and genetic mapping data. This set of overlapping clones will promote our knowledge of the structure of this chromosome and the function of its genes. PMID- 1406952 TI - Parents suppress reproduction and stimulate dispersal in opposite-sex juvenile white-footed mice. AB - Juvenile dispersal is sex-biased in many mammals and birds: one sex often disperses more often or farther than the other. Two hypotheses are generally presented for sex-biased dispersal. The first holds that juvenile dispersal reduces reproductive and/or resource competition between parents and same-sexed offspring. If so, presence of a parent on the natal home range should both promote dispersal of same-sex offspring and suppress reproduction of those that remain. The second is that juvenile dispersal reduces matings between parents and offspring, thus decreasing the likelihood of inbreeding depression. If so, presence of a parent should favour dispersal and reproductive suppression of offspring of the opposite sex. Here I present evidence that juvenile dispersal in white-footed mice, Peromyscus leucopus, is due to inbreeding avoidance. When population density was high, experimental removal of one parent delayed dispersal of opposite-sexed offspring and only the presence of the parents of opposite sex suppressed juvenile reproduction. PMID- 1406951 TI - Crystal structure of the met repressor-operator complex at 2.8 A resolution reveals DNA recognition by beta-strands. AB - The crystal structure of the met repressor-operator complex shows two dimeric repressor molecules bound to adjacent sites 8 base pairs apart on an 18-base-pair DNA fragment. Sequence specificity is achieved by insertion of double-stranded antiparallel protein beta-ribbons into the major groove of B-form DNA, with direct hydrogen-bonding between amino-acid side chains and the base pairs. The repressor also recognizes sequence-dependent distortion or flexibility of the operator phosphate backbone, conferring specificity even for inaccessible base pairs. PMID- 1406953 TI - Parental origin of chromosomes involved in the translocation t(9;22). AB - Functionally equivalent genetic maternal can be labelled by an epigenetic marking process and used differentially depending on whether its origin is maternal or paternal. This phenomenon is known as genomic imprinting and is manifested at either the chromosomal or gene level. Genomic imprinting seems to play an important role in cancer predisposition syndromes, and phenotypic consequences are evident in constitutional deletion syndromes and uniparental disomies. Moreover, there seems to be a preferential retention of paternal alleles in sporadic tumours such as Wilms' tumour, rhabdomyosarcoma, osteosarcoma and retinoblastoma. To investigate whether chromosomes involved in acquired abnormalities of haematologic neoplasms show a similar 'parent of origin' bias, we studied the inheritance of the translocated chromosomes 9 and 22 in cases of Philadelphia-chromosome-positive leukaemia, using unique specific chromosome band polymorphisms. Here we show that the translocated chromosome 9 was of paternal origin, whereas the translocated chromosomes 22 were derived exclusively from the maternal copy, in 11 cases with reliable polymorphisms. Our data therefore provide evidence that imprinting phenomena may play an important role in acquired tumour-specific chromosome rearrangements. PMID- 1406954 TI - Evidence for cooperative interactions in potassium channel gating. AB - Cloning and expression of voltage-activated potassium ion-channel complementary DNAs has confirmed that these channels are composed of four identical subunits, each containing a voltage sensor. It has been generally accepted that the voltage sensors must reach a permissive state through one or more conformational ('gating') transitions before the channel can open. To test whether each subunit gates independently, we have constructed cDNAs encoding four subunits on a single polypeptide chain, enabling us to specify the subunit stoichiometry. The gating of heterotetramers made up from combinations of subunits with different gating phenotypes strongly suggests that individual subunits gate cooperatively, rather than independently. Nonindependent subunit gating is consistent with measurements of the kinetics of K(+)-channel gating currents and in line with the widespread subunit cooperativity observed in other multisubunit proteins. PMID- 1406955 TI - Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max. AB - The c-myc protein (Myc) contains an amino-terminal transcriptional activation domain and a carboxy-terminal basic helix-loop-helix-leucine zipper (bHLH-Z) domain that directs dimerization of Myc with its partner, the max protein (Max), and promotes DNA binding to sites containing a CACGTG core consensus sequence. Despite these characteristics and the observation that Myc can modulate gene expression, a direct role for Myc or Max as transcription factors has never been demonstrated. Here we use Saccharomyces cerevisiae as an in vivo model system to show that the Myc protein is a sequence-specific transcriptional activator whose DNA binding is strictly dependent on dimerization with Max. Transactivation is mediated by the amino-terminal domain of Myc. We find that Max homodimers bind to the same DNA sequence as Myc+Max but that they fail to transactivate and thus can antagonize Myc+Max function. We also show that the Max HLH-Z domain has a higher affinity for the Myc HLH-Z domain than for itself, and suggest that the heterodimeric Myc+Max activator forms preferentially at equilibrium. PMID- 1406956 TI - Myc and Max proteins possess distinct transcriptional activities. AB - The Myc family proteins are thought to be involved in transcription because they have both a carboxy-terminal basic-helix-loop-helix-zipper (bHLH-Z) domain, common to a large class of transcription factors, and an amino-terminal fragment which, for c-Myc, has transactivating function when assayed in chimaeric constructs. In addition, c-, N- and L-Myc proteins heterodimerize, in vitro and in vivo, with the bHLH-Z protein Max. In vitro, Max homodimerizes but preferentially associates with Myc, which homodimerizes poorly. Furthermore Myc Max heterodimers specifically bind the nucleotide sequence CACGTG with higher affinity than either homodimer alone. The identification of Max and the specific DNA-binding activities of Myc and Max provides an opportunity for directly testing the transcriptional activities of these proteins in mammalian cells. We report here that Myc overexpression activates, whereas Max overexpression represses, transcription of a reporter gene. Max-induced repression is relieved by overexpression of c-Myc. Repression requires the DNA-binding domain of Max, whereas relief of repression requires the dimerization and transcriptional activation activities of Myc. Both effects require Myc-Max-binding sites in the reporter gene. PMID- 1406958 TI - Gene wars escalate as US official battles NIH over pursuit of patent. PMID- 1406959 TI - Europe tightens rules that govern homeopathic products. PMID- 1406957 TI - Probing met repressor-operator recognition in solution. AB - The three-dimensional crystal structure of the Escherichia coli methionine repressor, MetJ, complexed with a DNA operator fragment is described in an accompanying article. The complex exhibits several novel features of DNA-protein interaction. DNA sequence recognition is achieved largely by hydrogen-bond contacts between the bases and amino-acid side chains located on a beta-ribbon, a mode of recognition previously hypothesized on the basis of modelling of idealized beta-strands and DNA, and mutagenesis of the Salmonella phage P22 repressors Arc and Mnt. The complex comprises a pair of MetJ repressor dimers which bind to adjacent met-box sites on the DNA, and contact each other by means of a pair of antiparallel alpha-helices. Here we assess the importance of these contacts, and also of contacts that would be made between the C-helices of the protein and DNA in a previous model of the complex, by studying mutations aimed at disrupting them. The role of the carboxy-terminal helix face in operator binding was unclear, but we demonstrate that recognition of operator sequences occurs through side chains in the beta-strand motif and that dimer-dimer interactions are required for effective repression. PMID- 1406961 TI - Small businesses to get bigger slice of US research pie. PMID- 1406960 TI - Ludwig estate to support research. PMID- 1406962 TI - UK moves closer to free market for research funding. PMID- 1406963 TI - Congress supports breast cancer research by taking $210 million from military. PMID- 1406964 TI - Animal welfare. PMID- 1406965 TI - Cell biology. Every motion has its motor. PMID- 1406966 TI - Embryology. The quest for immortality. PMID- 1406967 TI - Checkpoint policing by p53. PMID- 1406968 TI - Marsupial Y chromosome encodes a homologue of the mouse Y-linked candidate spermatogenesis gene Ube1y. AB - The mammalian subclass Theria consists of infraclasses Metatheria (marsupials) and Eutheria ('placentals') which diverged from each other 120-150 million years before present (Myr BP). Both infraclasses have Y chromosome-dependent testis determination but direct molecular evidence linking the Metatherian and Eutherian Y chromosomes is lacking. Comparative analyses indicate that three mammalian genes have remained Y-linked for at least 80 Myr, since the divergence of the Eutherian orders from a common ancestor. These are Zfy, a gene encoding a transcription factor of the zinc-finger type; Sry, the putative primary testis determining gene; and Ube1y (formerly Sby or A1s9Y-1), a candidate for the mouse spermatogenesis gene Spy, encoding a ubiquitin-activating enzyme E1 homologue. Although in marspials Zfy homologues are autosomal, a Y homologue of Sry has recently been isolated. We report here the identification of a functional marsupial Y-linked homologue of the murine Ube1y gene establishing that Metatherian and Eutherian Y chromosomes diverged from a common ancestor. This extreme conservation indicates that Ube1y plays a critical role in male development. PMID- 1406969 TI - Evolution of sex determination and the Y chromosome: SRY-related sequences in marsupials. AB - In mammals, testis determination is under the control of the testis-determining factor borne by the Y chromosome. SRY, a gene cloned from the sex-determining region of the human Y chromosome, has been equated with the testis-determining factor in man and mouse. We have used a human SRY probe to identify and clone related genes from the Y chromosome of two marsupial species. Comparisons of eutherian and metatherian Y-located SRY sequences suggest rapid evolution of these genes, especially outside the region encoding the DNA-binding HMG box. The SRY homologues, together with the mouse Ube1y homologues, are the first genes to be identified on the marsupial Y chromosome. PMID- 1406970 TI - Microtubule-motor activity of a yeast centromere-binding protein complex. AB - During cell division, sister chromosomes segregate from each other on a microtubule-based structure called the mitotic spindle. Proteins bind to the centromere, a region of chromosomal DNA, to form the kinetochore, which mediates chromosome attachment to the mitotic spindle microtubules. In the budding yeast Saccharomyces cerevisiae, genetic analysis has shown that the 28-basepair (bp) CDEIII region of the 125-bp centromere DNA sequence (CEN sequence) is the main region controlling chromosome segregation in vivo. Therefore it is likely that proteins binding to the CDEIII region link the centromeres to the microtubules during mitosis. A complex of proteins (CBF3) that binds specifically to the CDEIII DNA sequence has been isolated by affinity chromatography. Here we describe kinetochore function in vitro. The CBF3 complex can link DNA to microtubules, and the complex contains a minus-end-directed microtubule-based motor. We suggest that microtubule-based motors form the fundamental link between microtubules and chromosomes at mitosis. PMID- 1406971 TI - CENP-E is a putative kinetochore motor that accumulates just before mitosis. AB - The mechanics of chromosome movement, mitotic spindle assembly and spindle elongation have long been central questions of cell biology. After attachment in prometaphase of a microtubule from one pole, duplicated chromosome pairs travel towards the pole in a rapid but discontinuous motion. This is followed by a slower congression towards the midplate as the chromosome pair orients with each kinetochore attached to the microtubules from the nearest pole. The pairs disjoin at anaphase and translocate to opposite poles and the interpolar distance increases. Here we identify CENP-E as a kinesin-like motor protein (M(r) 312,000) that accumulates in the G2 phase of the cell cycle. CENP-E associates with kinetochores during congression, relocates to the spindle midzone at anaphase, and is quantitatively discarded at the end of the cell division. CENP-E is likely to be one of the motors responsible for mammalian chromosome movement and/or spindle elongation. PMID- 1406972 TI - Mitotic spindle organization by a plus-end-directed microtubule motor. AB - Intracellular microtubule motor proteins may direct the motile properties and/or morphogenesis of the mitotic spindle (reviewed in ref. 3). The recent identification of kinesin-like proteins important for mitosis or meiosis indicates that kinesin-related proteins may play a universal role in eukaryotic cell division, but the precise function of such proteins in mitosis remains unknown. Here we use an in vitro assay for spindle assembly, derived from Xenopus egg extracts, to investigate the role of Eg5, a kinesin-like protein in Xenopus eggs. Eg5 is localized along spindle microtubules, and particularly enriched near spindle poles. Immunodepletion of Eg5 from egg extracts markedly reduces the extent of spindle formation in extracts, as does direct addition of anti-Eg5 antibodies. We also demonstrate that Eg5 is a plus-end-directed microtubule motor in vitro. Our results suggest a novel mechanism for the dynamic self-organization of spindle poles in mitosis. PMID- 1406973 TI - A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles. AB - Mitosis comprises a complex set of overlapping motile events, many of which involve microtubule-dependent motor enzymes. Here we describe a new member of the kinesin superfamily. The protein was originally identified as a spindle antigen by the CHO1 monoclonal antibody and shown to be required for mitotic progression. We have cloned the gene that encodes this antigen and found that its sequence contains a domain with strong sequence similarity to the motor domain of kinesin like proteins. The product of this gene, expressed in bacteria, can cross-bridge antiparallel microtubules in vitro, and in the presence of Mg-ATP, microtubules slide over one another in a fashion reminiscent of microtubule movements during spindle elongation. PMID- 1406974 TI - Autoimmune diabetes as a consequence of locally produced interleukin-2. AB - During cell differentiation in the thymus, self-reactive T cells can be generated. The majority of these seem to be deleted after intrathymic encounter with the relevant autoantigen. As all self antigens are unlikely to be present in the thymus, some autoreactive T cells may escape censorship. Here we study the fate of these cells using transgenic mice expressing the class I molecule H-2Kb (Kb) in the insulin-producing beta-cells of the pancreas. These mice were crossed with mice transgenic for genes encoding a Kb-specific T-cell antigen receptor (TCR) which could be detected using a clonotype-specific monoclonal antibody. Although T cells expressing the highest level of transgenic TCR were deleted intrathymically in double-transgenic mice, Kb-specific T cells were detected in the periphery. These cells caused the rejection of Kb-expressing skin grafts, but ignored islet Kb antigens even after priming. But when double-transgenic mice were crossed with transgenic mice expressing the lymphokine interleukin-2 in the pancreatic beta-cells, there was a rapid onset of diabetes. These results indicate that autoreactive T cells that ignore self antigens may cause autoimmune diabetes when provided with exogenous 'help' in the form of interleukin-2. PMID- 1406975 TI - Apoptotic cell death induced by c-myc is inhibited by bcl-2. AB - Apoptosis is a form of physiological cell death, characterized by chromatin condensation, cytoplasmic blebbing and DNA fragmentation, which often depends on RNA and protein synthesis by the dying cell. The c-myc proto-oncogene, usually implicated in cell transformation, differentiation and cell-cycle progression also has a central role in some forms of apoptosis. These opposing roles of myc in cell growth and death require that other gene products dictate the outcome of c-Myc expression on a cell. A candidate for such a modifying gene is bcl-2, whose product prolongs cell survival and blocks apoptosis in some systems. Here we demonstrate that Bcl-2 prevents apoptotic death induced by c-Myc, provide a mechanism whereby cells can express c-Myc without undergoing apoptosis, and give a possible explanation for the ability of Bcl-2 to synergize with c-Myc in cell transformation. PMID- 1406976 TI - Cooperative interaction between c-myc and bcl-2 proto-oncogenes. AB - The bcl-2 proto-oncogene is activated by translocation in a variety of B-lymphoid tumours and synergizes with the c-myc oncogene in tumour progression. The mechanism of synergy is unclear but bcl-2 expression inhibits apoptosis, a property presumably pertinent to its proto-oncogenic mode of action. We have shown that the c-myc gene is a potent inducer of apoptosis, in addition to its established role in mitogenesis. Here we show that expression of the bcl-2 protein, Bcl-2, specifically abrogates c-myc-induced apoptosis without affecting the c-myc mitogenic function. This provides a novel mechanism for oncogene cooperation, of potential importance both in carcinogenesis and in the evolution of drug resistance in tumours. PMID- 1406977 TI - New drug law to speed scientific review. AB - By charging drug companies 'user fees' that will be spent hiring new staff, the US Food and Drug Administration will reduce the time it takes to review new pharmaceuticals from an average of two years to one. PMID- 1406978 TI - Biodiversity supported. AB - Funding for a new programme, with only $1.5 million for grants, is hardly enough to scratch the surface. PMID- 1406979 TI - If biological diversity has a price, who sets it and who should benefit? PMID- 1406980 TI - New rules loom for US science funding as Congress passes a lean 1993 budget. PMID- 1406981 TI - Human Frontiers looks for leader in Europe; US wavers. PMID- 1406982 TI - User fees to hasten FDA review. PMID- 1406984 TI - Britain wrestles with EC rule on modified organisms. PMID- 1406985 TI - Overregulation could damage US biotechnology, says report. PMID- 1406983 TI - Brian Henderson named president of Salk Institute. PMID- 1406987 TI - Perkin-Elmer to buy Applied Biosystems to broaden markets. PMID- 1406986 TI - Nobel Prize given for work on protein phosphorylation. PMID- 1406989 TI - Semiprivate research: best of both worlds. PMID- 1406988 TI - HIV: to vaccinate or not to vaccinate? AB - "Improbability of effective vaccination against human immunodeficiency virus ...", declares the title of a new paper by Dr Albert Sabin. But three immunologists see flaws in his argument. PMID- 1406990 TI - RIKEN--Japan's leading light. PMID- 1406991 TI - Activins. No muscles, but what a brain. PMID- 1406992 TI - Neuropsychology. Drawing upon the mind's eye. PMID- 1406993 TI - Creative blocks: cell-cycle checkpoints and feedback controls. AB - Before division, cells must ensure that they finish DNA replication, DNA repair and chromosome segregation. They do so by using feedback controls which can detect the failure to complete replication, repair or spindle assembly to arrest the progress of the cell cycle at one of three checkpoints. Failures in feedback controls can contribute to the generation of cancer. PMID- 1406994 TI - Dissociation between mental imagery and object recognition in a brain-damaged patient. AB - Visual imagery is the creation of mental representations that share many features with veridical visual percepts. Studies of normal and brain-damaged people reinforce the view that visual imagery and visual perception are mediated by a common neural substrate and activate the same representations. Thus, brain damaged patients with intact vision who have an impairment in perception should have impaired visual imagery. Here we present evidence to the contrary from a patient with severely impaired object recognition (visual object agnosia) but with normal mental imagery. He draws objects in considerable detail from memory and uses information derived from mental images in a variety of tasks. In contrast, he cannot identify visually presented objects, even those he has drawn himself. He has normal visual acuity and intact perception of equally complex material in other domains. We conclude that rich internal representations can be activated to support visual imagery even when they cannot support visually mediated perception of objects. PMID- 1406995 TI - Hippocampus-dependent learning facilitated by a monoclonal antibody or D cycloserine. AB - Persistent neuronal plasticity, including that observed at some hippocampal synapses, requires N-methyl-D-aspartate (NMDA)-mediated transmission. NMDA receptor activation may be necessary for hippocampus-dependent learning as antagonists block acquisition in many such tasks. The behavioural effects of NMDA agonists are less well defined. We have shown that a monoclonal antibody (B6B21) displaced [3H]-glycine that was bound specifically to the NMDA receptor, and enhanced the opening of its integral cation channel in a glycine-like fashion, effects that were competitively antagonized by 7-chlorokynurenic acid. B6B21 also enhanced long-term potentiation in hippocampal slices. We report here that intraventricular infusions of B6B21 significantly enhances acquisition rates in hippocampus-dependent trace eye blink conditioning in rabbits, halving the number of trials required to reach a criterion of 80% conditioned responses. Peripheral injections of D-cycloserine, a partial agonist of the glycine site on the NMDA receptor which crosses the blood-brain barrier, also doubles rabbits' learning rates. Pseudoconditioning control experiments indicated a lack of nonspecific behavioural sensitization effects. Our data suggest that enhanced activation of the glycine coagonist site on the NMDA receptor/channel complex facilitates one form of associative learning and may be used in other learning tasks. PMID- 1406996 TI - Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase. AB - Reactive oxygen species have been implicated both in the ageing process and in degenerative diseases, including arthritis and cancer. Bacteria adapt to the lethal effects of oxidants such as hydrogen peroxide by inducing the expression of protective stress genes. Analogous responses have been identified in human cells. For example, haem oxygenase is a major stress protein in human cells treated with oxidants, and reactive oxygen intermediates activate NF-kappa B, a transcriptional regulator of genes involved in inflammatory and acute-phase responses. We report here the isolation and characterization of a novel complementary DNA (CL100) corresponding to a messenger RNA that is highly inducible by oxidative stress and heat shock in human skin cells. The cDNA contains an open reading frame specifying a protein of M(r) 39.3K with the structural features of a non-receptor-type protein-tyrosine phosphatase and which has significant amino-acid sequence similarity to a Tyr/Ser-protein phosphatase encoded by the late gene H1 of vaccinia virus. The purified protein encoded by the CL100 open reading frame expressed in bacteria has intrinsic phosphatase activity. Given the relationship between the levels of protein-tyrosine phosphorylation, receptor activity, cellular proliferation and cell-cycle control, the induction of this gene may play an important regulatory role in the human cellular response to environmental stress. PMID- 1406997 TI - A functional barrier to movement of lipids in polarized neurons. AB - In polarized neurons, axons and dendrites perform different functions, which are reflected in their different molecular organization. Studies on the sorting of viral and endogenous glycoproteins in epithelial cells and hippocampal neurons suggest that there may be similarities in the mechanism of sorting in these two cell types. The mechanisms that maintain the distinct composition of the two plasma membrane domains in these two cell types must, however, be different. We have proposed the existence of a functional barrier at the axonal hillock/initial segment which prevents the intermixing of membrane constituents. Here we test this hypothesis by fusing liposomes containing fluorescent phospholipids into the plasma membrane of polarized hippocampal cells in culture. Fusion was induced by lowering the pH and mediated by influenza virus haemagglutinin expressed on the axonal surface of neurons infected with fowl plague virus. Labelling was found exclusively on axons after fusion. Although the fused lipids were mobile on the axonal membrane, no labelling was detected on the cell body and dendritic surfaces. These results suggest that there is a diffusion barrier at the axonal hillock/initial segment which maintains the compositional differences between the axonal and somatodendritic domains. PMID- 1406998 TI - Identification of an amino acid-base contact in the GCN4-DNA complex by bromouracil-mediated photocrosslinking. AB - The bZIP DNA-binding proteins are characterized by a 50-amino-acid DNA binding and dimerization motif, consisting of a highly basic DNA-binding region ('b') followed by a leucine zipper dimerization region ('ZIP'). The best characterized bZIP DNA-binding protein is GCN4, a yeast transcriptional activator. GCN4 binds to a 9-base-pair two-fold-symmetric DNA site, 5'-A-4T-3G-2A-1C0T+1C+2A+3T+4-3' (refs 7-10). A detailed model known as the 'induced helical fork' model has been proposed for the structure of the GCN4-DNA complex. Using a site-specific bromouracil-mediated photocrosslinking method, we show here that the alanine at position 238 of GCN4 contacts, or is close to, the thymine 5-methyl of A.T at position +3 of the DNA site in the GCN4-DNA complex. Our results strongly support the induced helical fork model. Our site-specific bromouracil-mediated photocrosslinking method requires no prior information regarding the structure of the protein or the structure of the protein-DNA complex and should be generalizable to DNA-binding proteins that interact with the DNA major groove. PMID- 1406999 TI - Release of endogenous acetylcholine in the hypothalamus of conscious rats. AB - The release of endogenous acetylcholine was investigated by the push-pull technique. The posterior hypothalamus of conscious rats was superfused through a push-pull cannula with artificial cerebrospinal fluid (ACSF) which contained 1 mumol/l neostigmine. Acetylcholine was determined in the superfusate by high pressure liquid chromatography and electrochemical detection. Hypothalamic superfusion with potassium-rich (100 mmol/l) ACSF led to a pronounced increase in the release rate of acetylcholine. Tetrodotoxin (1 mumol/l) almost abolished the basal release of the neurotransmitter. Superfusion of the hypothalamus with atropine (10 or 50 mumol/l) led to a concentration-dependent increase, whereas superfusion with oxotremorine (50 mumol/l) inhibited the release rate of acetylcholine. It is concluded that acetylcholine released into the superfusate of the hypothalamus originates from cholinergic neurons. Furthermore, the release of acetylcholine seems to be modulated by muscarinic acetylcholine receptors, probably located on cholinergic neurons of the hypothalamus. PMID- 1407000 TI - Pharmacokinetic and thrombolytic properties of unglycosylated recombinant tissue type plasminogen activator (BM 06.021) produced in Escherichia coli. AB - Recombinant tissue-type plasminogen activator (rt-PA) was produced in Escherichia coli cells in order to obtain an unglycosylated rt-PA (BM 06.021) with increased thrombolytic potency due to altered pharmacokinetic properties. The pharmacokinetics were studied in rabbits upon intravenous infusion of 200 kU/kg over 30 min. The thrombolytic dose-response effects were evaluated in a rabbit model with 125I-labeled venous thrombi upon intravenous infusion over 4 h. The thrombolytic effects after intravenous bolus injection of 200 kU/kg BM 06.021 were investigated in a canine model of coronary artery thrombosis. All studies were performed comparing BM 06.021 with glycosylated rt-PA (alteplase). BM 06.021 demonstrated a longer (p less than 0.05) half-life (5.6 +/- 2.6 vs. 2.1 +/- 0.3 min) and a lower (p less than 0.05) clearance rate (7.5 +/- 0.8 vs. 22.2 +/- 3.1 ml.min-1.kg-1) than alteplase in rabbits upon intravenous infusion. The dose response curve of BM 06.021 for thrombolysis in a rabbit model of jugular vein thrombosis was located to the left of that for alteplase with a 2.1-fold lower effective dose of 50% thrombolysis (ED50) of BM 06.021 (207 vs. 436 kU/kg). Intravenous bolus injection of 200 kU/kg BM 06.021 induced the same reperfusion rate (4/6) as intravenous infusion of 800 kU/kg alteplase over 90 min in a canine model of coronary artery thrombosis. The residual thrombus wet weight did not significantly differ between BM 06.021 and alteplase (5.7 +/- 1.8 vs. 6.3 +/- 1.1 mg). The results indicate that unglycosylated rt-PA (BM 06.021) has a higher in vivo thrombolytic potency than glycosylated rt-PA (alteplase).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407001 TI - Dopamine and adrenaline, but not isoprenaline, are substrates for uptake and metabolism in isolated perfused lungs of rats. AB - The uptake and subsequent metabolism by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) of dopamine, adrenaline, isoprenaline and noradrenaline in isolated perfused lungs of rats has been examined. In lung preparations in which COMT and MAO were inhibited, the uptake of 3H-labelled dopamine, (-) adrenaline and (-)-noradrenaline, but not (+/-)-isoprenaline, was reduced by cocaine (10 or 100 mumol/l). The rank order of the Km values of the amines that were substrates for uptake in the lungs were: dopamine (0.246 mumol/l) less than noradrenaline (0.967 mumol/l) less than adrenaline (3.32 mumol/l). These results are consistent with transport of catecholamines in rat lungs by Uptake1. In lung preparations with COMT and MAO intact, dopamine and noradrenaline were removed from the circulation (50% and 32%, respectively) and mainly metabolized. There was very little (3.0%) removal of isoprenaline by the lungs and adrenaline was not included in this part of the study. In lung preparations in which only MAO was inhibited, the rank order of COMT activity for O-methylation of the amines was dopamine much much greater than noradrenaline greater than or equal to adrenaline (kCOMT values: 4.98 min-1, 0.357 min-1 and 0.234 min-1, respectively). If dopamine or adrenaline are perfused through the pulmonary circulation in isolated lungs of the rat, they are taken up and then metabolized by COMT and MAO, as also occurs for noradrenaline. Isoprenaline is not a substrate for uptake in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407002 TI - Modulation by sigma ligands of N-methyl-D-aspartate-induced [3H]noradrenaline release in the rat hippocampus: G-protein dependency. AB - The effects of the high affinity sigma (sigma) ligands 1,3-di(2-tolyl)guanidine (DTG), (+)N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1- ethyl-but-3-en-1-yl-amine hydrochloride (JO-1784), (+)3-[3-hydroxyphenyl]-N-(1-propyl)piperidine hydrochloride [(+)3-PPP] and haloperidol were studied on N-methyl-D-aspartate (NMDA)-evoked release of [3H]noradrenaline (NA) from preloaded hippocampal slices made from Sprague-Dawley rats. The [3H]NA release was evoked once by a 4 min exposure to NMDA, 40 min after the beginning of superfusion with a Mg+(+)-free Krebs' solution. In the absence of any drug, NMDA evoked a concentration dependent [3H]NA release. Mg++ and EGTA abolished the [3H]NA release induced by NMDA. JO-1784 and (+)3-PPP potentiated in a concentration-dependent manner NMDA induced [3H]NA release, without affecting the basal outflow. DTG concentration dependently inhibited the overflow of [3H]NA evoked by NMDA, without affecting the basal efflux. Haloperidol, which did not modify NMDA-evoked [3H]NA release by itself, completely prevented the effects of JO-1784, (+)3-PPP and DTG. In contrast, spiperone, also a potent dopamine receptor antagonist but with low affinity for sigma binding sites, failed to prevent the potentiation of NMDA evoked release of [3H]NA by JO-1784 and (+)3-PPP. The possible involvement of Gi/o proteins in the modulation by sigma ligands of NMDA-evoked [3H]NA release in the rat hippocampus was also investigated. To this end, Gi/o proteins were inactivated with pertussis toxin (PTX), injected locally 3 to 11 days prior to the experiment or with in vitro preincubation with N-ethylmaleimide (NEM) for 30 min prior the experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407004 TI - Histamine levels and clonic convulsions of electrically-induced seizure in mice: the effects of alpha-fluoromethylhistidine and metoprine. AB - The purpose of this study was to investigate the possible role of the central histaminergic neuron system in electrically-induced seizure in mice. For this purpose, we examined the effects of intraperitoneal (i.p.) injections of histaminergic agents, such as L-histidine, metoprine, and alpha fluoromethylhistidine (FMH), on electrically-induced seizure. L-Histidine decreased the duration of clonic convulsion in electrically-induced seizure, but not affected that of tonic convulsion. This effect of L-histidine was antagonized by pretreatment with FMH, indicating that it was due to histamine formed by decarboxylation of L-histidine in the central nervous system. The anticonvulsive effect of L-histidine was also reduced by the H1-antagonist pyrilamine, but not by the H2-antagonist zolantidine, indicating that the effect on electrically induced seizure is mediated through central H1-receptors. Metoprine, which increased the histamine levels in the cerebral cortex, diencephalon and midbrain of mice, decreased the duration of clonic convulsions dose-dependently. Conversely, FMH, which decreased the brain histamine levels, increased the duration of clonic convulsions. Good inverse correlations were found between the duration of clonic convulsions and brain histamine levels, especially in the diencephalon: the histamine levels were inversely proportional to the duration of clonic convulsions. No correlation was found between the duration of tonic convulsions and brain histamine levels. These results suggest that the histaminergic neuron system is important in inhibition of the duration of clonic convulsion on electrically induced seizure in mice. PMID- 1407003 TI - Molecular structural basis of ligand selectivity for 5-HT2 versus 5-HT1C cortical receptors. AB - A molecular structural criterion of ligand selectivity for the 5-HT2 versus 5 HT1C receptor was hypothesized on the basis of radioligand binding data. Despite the large number of compounds which have been tested at both receptors, analysis of published data led to the identification of only five agents which are greater than 10-fold selective for the 5-HT2 versus the 5-HT1C receptor. Comparison of the two-dimensional structures revealed that, although these five compounds represent three distinct structural classes, they share a common structural feature located in the region hypothesized to be involved in receptor binding: a carbonyl or carboxyl oxygen interposed spatially between an aromatic ring and nitrogen atom. This structural feature was used to predict the relative selectivity of compounds that had not previously been analyzed at both the 5-HT2 and 5-HT1C receptors. All six drugs tested which contain the identified reactive carbonyl or carboxyl group were found to be selective for the 5-HT2 versus the 5 HT1C receptor with selectivity ratios ranging from 26 to 380. By contrast, three agents which are structurally similar but do not contain the reactive carbonyl or carboxyl group displayed equally high affinity for both receptor binding sites. Since the physiological roles of the 5-HT2 and 5-HT1C receptor are markedly different, it would be of potential clinical and scientific value to utilize this molecular structural feature to further identify chemical compounds which would selectively interact with only one of the two receptors. PMID- 1407005 TI - Calcium mobilization and its desensitization induced by endothelins and sarafotoxin in human astrocytoma cells (1321N1): comparison of histamine-induced calcium mobilization. AB - Intracellular free Ca2+ concentration ([Ca2+]i) was monitored in monolayer of 1321 N1 astrocytoma cells by using a fluorescent Ca2+ indicator fura-2. Endothelin-1 (ET-1), endothelin-2 (ET-2), and sarafotoxin Sb6 (SRTX) increased [Ca2+]i from 56 +/- 6 nM to 360 +/- 82, 120 +/- 51, 143 +/- 29 nM, respectively, immediately after their addition to the perfusate with maximum response of more than 0.1 microM of peptides. Endothelin-3 (less than 1 microM) did not affect [Ca2+]i. The increase in [Ca2+]i in response to either ET-1, ET-2, or SRTX could be almost completely inhibited by pretreating cells with ET-1 or ET-2. The homologous desensitization of [Ca2+]i induced by ETs and SRTX is in good agreement with their affinity toward an ETA receptors. The responses in [Ca2+]i by ETs and SRTX were not affected in the desensitized state induced by the pretreatment of histamine in the presence of extracellular Ca2+. However, the response in [Ca2+]i by ETs and SRTX were reduced in the desensitized state induced by pretreatment of histamine in the absence of extracellular Ca2+. These results indicate that depletion of the intracellular Ca2+ stores is responsible for the heterologous desensitization between ETs and histamine. PMID- 1407007 TI - Identification of a novel high affinity adenosine binding protein from bovine striatum. AB - In solubilized extracts from bovine striatal membranes three different binding sites for 5'-N-ethylcarboxamidoadenosine ([3H]NECA) were observed after separation of the extract by gel filtration on Sepharose CL-6B. The first peak was eluted in the void volume and contained the A2 adenosine receptor. In the second peak, [3H]NECA binding sites were eluted with a pharmacological profile characteristic of adenotin, a low affinity non-receptor adenosine binding protein. The third peak represented approximately 50% of the [3H]NECA binding activity. This site bound [3H]NECA in a reversible and saturable manner with KD of 17 nmol/l and a binding capacity of 11.3 pmol/mg protein. In competition experiments, adenosine, NECA, NAD, inosine, 5'-AMP and S-adenosyl-L-homocysteine were the most potent ligands. In contrast to adenosine receptors, this site did neither bind adenosine receptor antagonists nor the A2 selective agonist CGS 21,680 (2-[p-(2-carboxyethyl)phenethylamino]5'-N-ethylcarboxamidoadeno sin e). These results suggest the existence of a novel high affinity binding site for adenosine of unknown function in bovine striatum. PMID- 1407006 TI - Effects of taurine, homotaurine and GABA on hypothalamic and striatal dopamine metabolism. AB - To elucidate the effects of taurine on hypothalamic and striatal dopaminergic neurotransmission we compared its effects to those of gamma-aminobutyric acid (GABA) and homotaurine (a GABAA-receptor agonist) on hypothalamic and striatal concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and, in the case of striatum, 3 methoxytyramine (3-MT) in rats. In addition, hypothalamic and striatal 5 hydroxytryptamine (5-HT) und 5-hydroxyindoleacetic acid, hypothalamic noradrenaline (NA) and 3-methoxy-4-hydroxyphenylglycol sulfate, and pituitary DA concentrations were also measured. The amino acids were injected into the lateral brain ventricles of conscious male rats in doses of 10 and 36 mumol/rat, and rat were sacrificed 15 and 60 min later, respectively. Homotaurine (by 11%) but not the other two amino acids elevated striatal DA, whereas hypothalamic DA was increased by both taurine (36%) and homotaurine (31%). All three amino acids at 36 mumol elevated striatal DOPAC, homotaurine (51%) more than taurine (31%) or GABA (30%), and hypothalamic DOPAC, both taurine (102%) and homotaurine (82%) clearly more than GABA (34%). Neither striatal nor hypothalamic HVA was altered by any of the amino acids. At 10 mumol the amino acids decreased striatal 3-MT by about 40%. At 36 mumol taurine and homotaurine reduced 3-MT by about 70%, whereas increasing the dose of GABA did not further reduce 3-MT. Both taurine and homotaurine at 36 mumol decreased hypothalamic NA content. Neither hypothalamic nor striatal 5-HT metabolism was altered. In the neurointermediate lobe of the pituitary gland taurine at 10 mumol but not at 36 mumol slightly (20%) increased DA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407008 TI - Veratridine causes the Ca(2+)-dependent increase in diacylglycerol formation and translocation of protein kinase C to membranes in cultured bovine adrenal medullary cells. AB - Our previous studies suggested that protein kinase C is involved in the veratridine (an activator of voltage-dependent Na+ channels)-induced phosphorylation and activation of tyrosine hydroxylase as well as the synthesis of catecholamines in adrenal medulla (Uezono et al. 1989). In the present study, we investigated whether treatment of cultured bovine adrenal medullary cells with veratridine causes the accumulation of diacylglycerol, a physiological activator of protein kinase C and the translocation of protein kinase C from cytosol to membrane, a process required for protein kinase C activation. Veratridine (100 mumol/l) increased diacylglycerol level about 2.2 fold in a monophasic manner, with peaking at 5 min and declining toward the basal level within 20 min. Veratridine also increased membrane protein kinase C from 15.6% to 26.9% of total protein kinase C in a time-course similar to that of diacylglycerol accumulation. Both stimulatory effects of veratridine were inhibited by tetrodotoxin and not observed in Ca(2+)-free, EGTA-containing medium. Amiloride, an inhibitor of Na+/Ca2+ and Na+/H+ exchange, did not alter veratridine-induced events. These results suggest that veratridine-induced Ca2+ influx contributes to the accumulation of diacylglycerol and the activation of protein kinase C in adrenal medullary cells. PMID- 1407010 TI - "5-HT1R" or 5-HT1D sites? Evidence for 5-HT1D binding sites in rabbit brain. AB - Radioligand binding studies were performed in membranes of rabbit whole brain and striatum using the novel iodinated radioligand for 5-hydroxytryptamine 5-HT1B and 5-HT1D sites, Serotonin-5-O-Carboxymethyl-Glycyl[125I]Tyrosinamide ([125I]GTI). [125I]GTI labelled a finite number of high affinity sites in rabbit brain membranes, Bmax = 191 +/- 47 fmol/mg protein, pKD (-log mol/l) = 8.50 +/- 0.13, n = 5. The pharmacological profile of [125I]GTI binding was fully comparable to that reported previously in human and other brain preparations known to possess 5 HT1D sites (using either [3H]5-HT or [125I]GTI) and displayed a characteristic rank order of affinity: 5-carboxamido-tryptamine greater than 5-HT = dihydroergotamine greater than or equal to ergotamine greater than or equal to sumatriptan greater than or equal to CGS 12066 greater than or equal to metergoline greater than yohimbine greater than or equal to methysergide greater than ICYP greater than 8-OH-DPAT greater than or equal to CP 93129 greater than ( )pindolol greater than ketanserin greater than isamoltane greater than mesulergine greater than corynanthine greater than buspirone greater than MDL 72222. Autoradiographic studies were performed on rabbit brain slices using [3H]5 HT in the presence of 100 nmol/l 8-OH-DPAT and mesulergine (in order to mask 5 HT1A and 5-HT1C binding sites) and [125I]CYP (iodocyanopindolol) in the presence of 3 mumol/l isoprenaline and 100 nmol/l 8-OH-DPAT (in order to mask beta adrenoceptor and 5-HT1A binding sites). There was no detectable specific binding of [125I]CYP through the brain, thus excluding the presence of 5-HT1B sites in rabbit brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407009 TI - 5-HT1D binding sites in various species: similar pharmacological profile in dog, monkey, calf, guinea-pig and human brain membranes. AB - Radioligand binding studies were performed in membranes of calf caudate, guinea pig cortex, dog caudate and whole brain, monkey caudate and whole brain, and human caudate using the novel iodinated radioligand, Serotonin-5-O-Carboxymethyl Glycyl[125I] Tyrosinamide (abbreviated [125I]GTI for the sake of simplicity), a ligand known to label 5-HT1B and 5-HT1D sites. In all membrane preparations tested, [125I]GTI labelled high affinity sites with the following rank order of affinity: 5-carboxamidotryptamine greater than 5-HT = DHE = ergotamine greater than or equal to sumatriptan greater than or equal to metergoline = CGS 12066 greater than or equal to yohimbine = methysergide greater than or equal to methiothepin greater than 8-OH-DPAT greater than or equal to mianserin greater than or equal to CP 93129 greater than or equal to (-)pindolol = ketanserin greater than or equal to isamoltane = mesulergine greater than or equal to corynanthine = spiperone greater than MDL 72222. The affinity profiles were very similar in the membranes of the different species, especially in dog, monkey and human brain. The pharmacological profile of [125I]GTI binding (determined with up to 25 different drugs) was fully comparable to the binding profile reported previously in human substantia nigra (using [125I]GTI) or in a variety of brain preparations known to contain 5-HT1D sites using [3H]5-HT as a radioligand.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407011 TI - M1 muscarinic receptors mediate intracellular calcium release in NB-OK1 human neuroblastoma cells. AB - Muscarine acetylcholine receptors were characterized in NB-OK1 cells using radioligand (3H-NMS) binding experiments and second messenger (calcium and phosphatidylinositol (PI) turnover) studies. In radioligand binding experiments the displacement curves of pirenzepine (KI = 1.3 x 10(-8) M), AF-DX 116 (KI = 8.2 x 10(-7) M), methoctramine (KI = 8.4 x 10(-8) M) and parafluorohexahydrosiladifenidol (pF-HHSiD) (KI = 1.8 x 10(-8) M) were monophasic and indicated the presence of M1 muscarinic receptors. Schild analysis with the muscarinic antagonists pirenzepine, AF-DX 116, methoctramine and pF-HHSiD yielded pA2 values of 8.40 +/- 0.13, 6.48 +/- 0.09, 7.61 +/- 0.12 and 7.22 +/- 0.08 in the calcium experiments and pA2 values of 8.13 +/- 0.30 and 6.26 +/- 0.26, 7.65 +/- 0.16 and 7.46 +/- 0.11, respectively, in the PI turnover experiments. These results indicate that both the carbachol-induced increase in intracellular calcium and the increase in PI turnover are mediated by M1 muscarinic receptors. In calcium free buffer, stimulation with carbachol induced similar responses to those seen under control conditions. From functional and radioligand binding experiments we conclude that the muscarinic receptor expressed in NB-OK1 cells is the M1 subtype. In addition, the M1 receptor-induced calcium response is related to PI turnover and is independent on extracellular calcium. PMID- 1407012 TI - Biochemical and pharmacological properties of a peripherally acting catechol-O methyltransferase inhibitor entacapone. AB - Entacapone, OR-611, was found to be a potent peripherally acting inhibitor of catechol-O-methyltransferase (COMT). IC50 values of 10 nmol/l and 160 nmol/l were obtained for rat duodenum and liver-soluble COMT, respectively. There were no effects on other catecholamine metabolizing enzymes. Entacapone showed reversible, tight-binding type of inhibition of soluble rat liver COMT with a Ki value of 14 nmol/l and it also caused 50% inhibition of rat duodenal, erythrocyte, liver and striatal COMT activity 1 h after oral dosing with 1.1, 5.4, 6.7 and 24.2 mg/kg, respectively. However, penetration of entacapone into the brain was poor, since the formation of homovanillic acid (HVA), the O-methyl metabolite of dopamine in the striatum, was not reduced, even after the highest dose of 30 mg/kg. In rat blood serum, the concentration of 3-O-methyldopa (3OMD), the O-methylated product of L-dopa, was reduced in a dose-dependent manner, and the concentration of L-dopa was increased after the administration of entacapone (3-30 mg/kg p.o.) together with L-dopa + carbidopa. These changes were reflected, in the striatum, by a significant rise in the dopamine concentration and a reduction in the 3OMD concentration. Consequently, when entacapone was added to the treatment with L-dopa + carbidopa, the dose of L-dopa could be lowered from 50 mg/kg to 15 mg/kg in order to produce the same striatal dopamine concentrations as with 50 + 50 mg/kg of L-dopa + carbidopa alone. PMID- 1407013 TI - Regional differences in evoked dopamine efflux in brain slices of rat anterior and posterior caudate putamen. AB - Fast cyclic voltammetry using carbon fibre microelectrodes in rat brain slices, was used to investigate regional differences in electrically-evoked dopamine (DA) efflux at 10 different sites in the anterior caudate putamen (aCPu) and 10 sites in the posterior caudate putamen (pCPu). For each site DA overflow was evoked by both single pulse (1P) stimulation and by trains of 25 pulses applied at a frequency of 50 Hz (25P/50 Hz). Peak DA efflux evoked by 1P was about 58% greater in the aCPu (0.19 mumol/l DA) than in the pCPu (0.12 mumol/l DA), but showed no mediolateral variation in either region. Peak DA efflux evoked by 25P/50 Hz relative to 1P efflux also varied between the two regions; the aCPu contained predominantly low ratio (25P/50 Hz: 1P) sites ranging from 1.47 to 3.71, whereas in the pCPu these ratios were higher, ranging from 2.73 to 9.40, and were particularly high in the dorsomedial region of the pCPu. Efflux detected in low ratio sites of the aCPu showed little dependence on the frequency (10 to 500 Hz), or the number of pulses (5 to 20) in a train. By contrast DA efflux evoked in high ratio sites of the pCPu responded in a pulse and frequency dependent manner, the maximum ratio (approximately 8 times 1P) being at 20P/20 Hz. Interestingly the frequency response relationship obtained in the pCPu resembled the profile observed in the nucleus accumbens (NAc). Voltammetric evidence and experiments with selective reuptake blockers indicated that only DA was measured in our studies and 5-HT did not significantly contribute to the frequency dependent pattern of efflux detected in high ratio sites of the pCPu, where striatal 5-HT concentrations are highest. Experiments with the selective D2 receptor antagonists metoclopramide or (-)sulpiride revealed that under our experimental conditions, DA efflux in the aCPu was not modulated by DA autoreceptor activation. By contrast, autoreceptor modulation did occur in high ratio sites of the pCPu at stimulations lasting longer than approximately 1000 ms. These observations support the concept that the caudate putamen is heterogeneously organised with respect to the frequency characteristics of evoked DA release. The factors controlling frequency dependent release under these conditions may be a function of A10 innervation, since high ratio release sites occur in areas where the density of such innervation is greatest, for example, the dorsomedial pCPu. This is supported by the observation that high ratio release sites are also found in the NAc, which receives dopaminergic fibres predominantly from an A10 region.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1407014 TI - Biotransformation of L-dopa in striatum and substantia nigra of rats with a unilateral, nigrostriatal lesion: a microdialysis study. AB - Microdialysis was used to study the biotransformation of L-DOPA in the striatum and substantia nigra of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. The animals were pretreated with carbidopa (50 mg/kg p.o.) for 5 days. They were anaesthetized, and microdialysis probes were implanted into the intact and denervated striatum and into the intact and lesioned substantia nigra. The biotransformation of L-DOPA (5 mg/kg i.p.) in these regions was investigated. These results were compared with those obtained after administration of a much higher dose of L-DOPA (100 mg/kg i.p.). Changes in extracellular L-DOPA, 3-O-methyldopa (3-OMD), dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined by HPLC with electrochemical detection. Although rats with a unilateral nigrostriatal lesion did not show rotational behaviour after 5 mg/kg L-DOPA, DA levels were increased significantly both in the intact and the denervated striatum and in the intact and the lesioned substantia nigra. This increase was most pronounced in the denervated striatum. At 100 mg/kg L-DOPA, the increases in extracellular dopamine in intact and denervated striatum were about twice as high as the increases observed at the lower dose. A similar increase was observed in the intact substantia nigra. However, in the lesioned substantia nigra there was a fourfold increase. L-DOPA, at both doses, was evenly distributed between the brain areas studied and the lesion had no effect on the uptake of the drug at the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407015 TI - Predominance of oxidative deamination in the metabolism of exogenous noradrenaline by the normal and chemically denervated human uterine artery. AB - Longitudinal strips were prepared from human uterine arteries obtained at hysterectomy. The artery had a low content of noradrenaline and dopamine, contrasting with a high content of the deaminated catechols, dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA), which together represented 98% of endogenous catechols. When incubated with 3H-noradrenaline (0.1 mumol/l), the uterine artery removed, accumulated and metabolized noradrenaline. Deaminated metabolites predominated, DOMA being the most abundant metabolite. Cocaine markedly reduced the accumulation of 3H-noradrenaline and abolished 3H-DOPEG formation, but did not change 3H-DOMA. Selective monoamine oxidase (MAO) inhibitors (clorgyline, selegiline and 2-amino ethyl carboxamide derivatives) caused a marked decrease in the amounts of 3H-DOPEG, 3H-DOMA and 3H O-methylated and deaminated metabolites (OMDA) formed by the tissue and an increase in 3H-normetanephrine (NMN) formation. Inhibition of catechol-O methyltransferase suppressed NMN formation and reduced that of OMDA; hydrocortisone slightly depressed the formation of DOMA and OMDA. Homogenates of the uterine artery deaminated 3H-5-HT, 14C-phenylethylamine and 3H-tyramine; inhibition curves of the deamination of 3H-tyramine by clorgyline and selegiline were compatible with the presence of both MOA A and MOA B. Exposure of the strips to 6-hydroxydopamine (1.5 mmol/l for 20 min; 3 exposure periods followed by washout periods of 15,15 and 30 min) resulted in complete and selective chemical denervation of the arterial tissue. This chemical denervation had effects which were similar to those of cocaine. The 2-amino ethyl carboxyamide derivatives markedly reduced the formation of deaminated metabolites by the denervated strips.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407016 TI - An analysis of the inhibitory effects of prazosin on the phenylephrine response curves of the rat aorta. AB - On the endothelium-intact rat aorta some studies have shown prazosin to cause nonparallel rightward shifts of alpha 1-adrenoceptor agonist response curves. The aim of the present study was to analyze the inhibitory effect of prazosin on the phenylephrine responses of the endothelium-intact and endothelium-denuded rat aorta. Firstly I used phenoxybenzamine treatment to characterize the phenylephrine responses. The KA values for phenylephrine were 0.13-0.18 microM and 0.07-0.16 microM in the endothelium-intact and endothelium-denuded rat aorta, respectively. In order to produce maximal responses of the endothelium-intact or- denuded preparation, phenylephrine had to occupy 95-99% of the alpha 1 adrenoceptors. Secondly I compared the inhibitory effects of phentolamine and prazosin on the endothelium-intact rat aorta. Phentolamine at 0.1 and 1 microM caused parallel rightward shifts of phenylephrine response curves with no effect on phenylephrine maximal responses (phentolamine pA2 = 7.9). The inhibitory effects of phentolamine were readily reversible. Prazosin at 0.1-10 nM caused nonparallel rightward shifts of the phenylephrine response curves with a depression of the maximal response. These inhibitory effects of prazosin were either irreversible or only very slowly reversible in drug-free solution and slowly reversible in the presence of phentolamine. Ninety min was required for the inhibitory effect of prazosin to reach equilibrium whereas phentolamine was at equilibrium after 45 min. Finally I have characterized the inhibitory actions of prazosin on the endothelium-denuded rat aorta. Prazosin caused parallel rightward shifts of phenylephrine response curves with no effect on phenylephrine maximal responses. The inhibitory effects of prazosin were at equilibrium after 45 min and were readily reversible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407017 TI - Spinal 5-HT pathways and the antinociception induced by intramedullary clonidine in rats. AB - The possible involvement of spinal 5-hydroxytryptamine (5-HT) pathways in antinociception induced by microinjection of clonidine into the ventrolateral surface of the medulla oblongata was investigated in rats. Microinjection of clonidine (10-20 micrograms), but not yohimbine (1 microgram) or 0.9% saline, into the lateral medulla prolonged the hot plate latency in rats. This clonidine induced antinociception was abolished by intramedullary injection of the alpha 2 adrenoceptor antagonist, yohimbine. Selective destruction of spinal 5-HT neurons produced by intraspinal injection of 5,7-dihydroxytryptamine (5,7-DHT; 10 micrograms) or postsynaptic blockade of spinal 5-HT receptors produced by intrathecal injection of cyproheptadine (1 microgram; a mixed 5-HT1/5-HT2 antagonist) also abolished clonidine-induced antinociception. Rats given 5,7-DHT intraspinally or cyproheptadine intrathecally showed a decrease in hot plate latency as compared with the controls. In anesthetized rats, the 5-HT release from the thoracic spinal cord was enhanced by microinjection of clonidine into the lateral medulla. This enhanced spinal 5-HT release evoked by intramedullary injection of clonidine was abolished by pretreatment of rats with intraspinal injection of 5,7-DHT. These results indicate that 5-HT pathways to the spinal cord mediate the antinociceptive effect induced by microinjection of clonidine into the ventrolateral surface of the medulla oblongata in rats. PMID- 1407019 TI - Evidence for a link between specific proteolysis and inhibition of [3H] noradrenaline release by the light chain of tetanus toxin. AB - The light chain of tetanus toxin is known to inhibit the Ca(2+)-evoked release of [3H]-noradrenaline from digitonin-permeabilized bovine adrenomedullary cells in culture but does not change the basal outflow or the total cellular radioactivity. Evidence for the involvement of proteolysis in this effect was obtained by three approaches. First, the permeabilized cells were exposed to a series of enzymes. The endoproteinase Glu-C mimicked the inhibition produced by the light chain. Second, protease inhibitors of different specificities were assessed for blockade of the action of light chain on [3H]-noradrenaline release from permeabilized cells. Blockade was complete with EDTA (2.5 mmol/l) or 1,10-o phenanthroline (1 mmol/l), and absent with the highest concentrations tested of diisopropylfluorophosphate, phenylmethylsulfonyl fluoride, pepstatin, leupeptin, bestatin, phosphoramidon, thiorphan or trans-epoxysuccinic acid (E64) which is regarded as an inhibitor of thiol proteases. This inhibitor spectrum suggested that light chain might be a metalloprotease. Finally a sequence-His-Glu-Leu-X-His occurring in the light chains of tetanus toxin and of the botulinum neurotoxins A, C, D, E was also found in many endoproteinases and an aminopeptidase. The motif is known to constitute their active site and to bind Zn2+. In fact Zn2+ (0.6-0.9 mol/mol) was found in thoroughly dialysed two-chain tetanus toxin. The three approaches jointly support the hypothesis that the light chain of tetanus toxin, and probably of all clostridial neurotoxins, inhibits [3H]-noradrenaline release from adrenomedullary cells by degradation of (a) specific, still unknown protein(s) involved in exocytosis. PMID- 1407018 TI - Effect of calcium antagonists (omega-conotoxin GVIA, verapamil, gallopamil, diltiazem) on bronchial smooth muscle contractions induced by soman. AB - The effect of the calcium antagonists omega-conotoxin GVIA, verapamil, gallopamil and diltiazem was investigated on in vitro bronchial smooth muscle contraction in the rat induced by the nerve agent soman. Soman inhibits the acetylcholinesterase activity irreversibly. The effect of the calcium channel antagonists on contractions induced by electrical field stimulation and carbachol was also investigated, in order to elucidate the mechanism by which calcium antagonists inhibit the soman induced contraction. omega-Conotoxin GVIA reduced the bronchial smooth muscle contraction induced by electrical field stimulation with an almost complete inhibition at approximately 1.0 x 10(-6) M. The soman induced contraction was only inhibited by 15% at a concentration of 3.0 x 10(-6) M omega conotoxin GVIA. The organic calcium antagonists verapamil, gallopamil and diltiazem reduced both electrically and soman induced smooth muscle contraction. Complete inhibition of the contractions induced by soman was achieved at 1.4 x 10(-4) M for verapamil and gallopamil, while diltiazem inhibited the contraction to 7% of control at 1.4 x 10(-4) M. Verapamil, gallopamil and diltiazem increased the EC50 for carbachol significantly, while omega-conotoxin GVIA had no effect. None of the calcium antagonists had any effect on the maximal contraction induced by carbachol. Verapamil, gallopamil and diltiazem blocked, however, sub-maximal contractions induced by carbachol (10(-7)-10(-5) M) resulting in a right-shift of the dose response curve. The results show that omega-conotoxin GVIA inhibits the calcium-dependent release of acetylcholine which causes contraction of airway smooth muscle, while it has no effect on smooth muscle contraction induced by soman.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407020 TI - Evidence for direct vasoconstrictor activity of melatonin in "pressurized" segments of isolated caudal artery from juvenile rats. AB - Responses of isolated, 60 mmHg 'pressurized' segments of the distal caudal artery of adult and juvenile Wistar rats to melatonin and the selective alpha 2 adrenoceptor agonist 5-bromo-6-[2-imidazolin-2-ylamino]-quinoxaline bitartrate (UK-14304) were examined using the Halpern pressure myograph. Melatonin showed no direct vasoconstrictor activity in vessels from adult rats, whereas UK-14304 produced moderate vasoconstriction (pD2-7.43 +/- 0.09). In the presence of phenylephrine-induced tone, melatonin produced a variable but small constrictor response (less than 10 microns reduction in diameter) in some vessels; the response to 1 mumol/l UK-14304 was less than in the absence of tone. In vessels isolated from juvenile rats, melatonin caused concentration-dependent vasoconstriction with a maximum response about 70% of the maximum response elicited by UK-14304. Vessels from juvenile rats were more sensitive to melatonin (pD2-9.40 +/- 0.07) than they were to UK-14304 (pD2-8.12 +/- 0.14). In the presence of phenylephrine-induced tone, the vasoconstrictor responses to both melatonin and IK-14304 were markedly less; the sensitivity to melatonin was not different from that seen in the absence of tone. These findings indicate that 'pressurized' segments of the isolated distal caudal artery may provide a simple and convenient, functional model of melatonin receptors. The findings also appear to implicate melatonin in thermoregulatory processes in juvenile rats. PMID- 1407021 TI - Tetanus toxoid vs. tetanus antitoxin. PMID- 1407022 TI - Treating anaphylaxis. PMID- 1407023 TI - Prostate cancer in North Carolina. PMID- 1407024 TI - Why does the injured drunk driver escape arrest and conviction? A case presentation and discussion by health care and law enforcement professionals. AB - Serious injury protects the drunk driver from prosecution and conviction for driving drunk. This escape from liability occurs despite the fact that almost half of all traffic fatalities are attributable to alcohol. Consequently, the drunk driver who is injured may resume driving as soon as he is physically able to do so, thereby becoming a renewed threat to himself and others. On the other hand, a conviction for driving while impaired (DWI) results in loss of the driving privilege, reducing exposure of other drivers to a public health hazard. A DWI conviction may also stimulate the drunk driver to seek treatment for alcoholism. Unless they are prosecuted, even seriously injured drunk drivers are seldom referred for alcoholism counseling or treatment. To explore the reasons for this continuing cycle of impairment and injury, a panel of experts from the fields of health care and law enforcement was convened on October 30, 1991, during the Third Annual North Carolina Conference on Injury Control. The panel considered the hypothetical case of an alcohol-related motor vehicle crash in which a passenger was killed. We present here an edited transcript from that conference. PMID- 1407025 TI - Blood alcohol concentration in motor vehicle crash victims. A survey of North Carolina emergency physician attitudes and utilization patterns. PMID- 1407026 TI - Fingerstick detection of hypoglycemia can prevent dangerous doses of dextrose. PMID- 1407027 TI - Healthy youths. PMID- 1407028 TI - Where are we and how did we get here? Federal regulation of the office laboratory. PMID- 1407029 TI - Shock and prolonged muscle cramps after intravenous insulin therapy. PMID- 1407030 TI - It's all in our minds--or is it? Dorothea's fables from the psychiatric/medical interface. PMID- 1407031 TI - Physicians' forum. To speak or not to speak. PMID- 1407032 TI - Has price gone too far? PMID- 1407033 TI - The time is here to address ethical issues in dialysis, but criteria too harsh. PMID- 1407034 TI - Is the burden of dialysis on the patient--or the provider? PMID- 1407035 TI - 1990 transplant statistics show more hard times ahead. PMID- 1407036 TI - Practical application of continuous quality improvement in renal care. PMID- 1407037 TI - Measuring physician-patient contact: how much is enough? PMID- 1407038 TI - Doctor-patient relationship unique in dialysis, needs improvement. PMID- 1407039 TI - Nephrology nursing certification: a look at progress. PMID- 1407040 TI - NKF lends direction to defining the patient-care technician role. PMID- 1407042 TI - New CLIA regulations: they create a more complex definition for laboratories. PMID- 1407043 TI - Future trends and issues in erythropoietin. Part 1. PMID- 1407041 TI - AIDS and ESRD: a dilemma for the renal community. PMID- 1407044 TI - How will wonder drugs impact the aging ESRD population of the future? PMID- 1407045 TI - Renal administrators think dialysis unit should be safe harbor. The National Renal Administrators Association. PMID- 1407046 TI - Sutton's law applied to renal care. PMID- 1407047 TI - Three deaths associated with excess aluminum in dialysate. PMID- 1407049 TI - Responses and questions directing the future of nephrology. PMID- 1407048 TI - Rosen: reuse shouldn't be an option. PMID- 1407050 TI - Selection criteria cannot identify a patient's quality of life on dialysis. PMID- 1407051 TI - Rehabilitation: "the unwanted orphan of the ESRD community". PMID- 1407052 TI - Confidentiality important. PMID- 1407053 TI - OPOs should play a neutral role. PMID- 1407054 TI - Financial incentives in organ donation: can they work? PMID- 1407055 TI - Rehab: should we just give up? PMID- 1407056 TI - Exercise is making a difference to transplant patients. Interview by Cynthia J Knapp. PMID- 1407057 TI - Georgia program gives young adults a new outlook on life. Interview by Cynthia J Knapp. PMID- 1407058 TI - The ANNA/NANT task force findings. PMID- 1407059 TI - Delegation of nursing tasks: a guide for ESRD facilities. PMID- 1407060 TI - What are the incentives for the ESRD patient? PMID- 1407061 TI - Clarifications needed on AIDS/ESRD article. PMID- 1407062 TI - Cyclosporine and the financial plight of organ transplant recipients. PMID- 1407063 TI - Mistrust in health care hurting organ donation. PMID- 1407065 TI - HCFA data shows incidence of ESRD among elderly took big jump in 1989. PMID- 1407064 TI - Issues in rehabilitation. Part II. Rehabilitation of the renal patient:should we just give up? PMID- 1407067 TI - The top 50 renal transplant centers in 1991. PMID- 1407066 TI - Investigation may close even more doors for transient patients. PMID- 1407068 TI - Medical judgment versus civil rights. PMID- 1407070 TI - Why I chose home hemodialysis. PMID- 1407069 TI - Ingredients of a successful home hemodialysis program. Part II. PMID- 1407071 TI - HHD gives patient control of life. PMID- 1407072 TI - Intravenous versus oral calcitriol therapy: is there a clinical difference? PMID- 1407073 TI - Viewpoint: government regulations "politicizing" transplantation. PMID- 1407074 TI - Dialysis units charged with denying transient dialysis care to HIV+ patients. PMID- 1407075 TI - Denials from dialysis units were "flagrant," says GWU social worker. Interview by Mark E. Neumann. PMID- 1407076 TI - What nurses can do for health care reform. PMID- 1407077 TI - The Gag Rule: gag ME. PMID- 1407078 TI - Continuing education in state hospitals using external consultants. AB - A continuing education project for registered nurses in a state psychiatric hospital was implemented collaboratively by a nurse administrator and two nurse consultants. This program sought to enhance the nurses' knowledge of psychiatric mental health nursing practice and prepare them to take the American Nurses Association certification examination for psychiatric-mental health nursing. The project was based on the premise that the nursing departments that offer educational services for their nurses foster professional competency and maintain current standards of nursing care. Twenty-one registered nurses volunteered for and completed the 16-week program. Improvements in their knowledge base were evidenced by mean test scores. A t-test analysis indicated a significant difference. The pretest mean score was 70.2%, the posttest mean score 79.4%. Mean scores varied with the education level of the nurses. PMID- 1407079 TI - Early precursors of psychiatric nursing, 1838-1907. AB - Care of the insane during the 17th and 18th centuries was undeniably grim until the advent of moral therapy. Wasserbauer and Brodie explore the humanistic approach that laid the groundwork for early psychiatric nursing. PMID- 1407080 TI - Upward mobility for LPNs: a vision made reality. AB - A recurrent theme in the nursing literature is the shortage of realistic, long term solutions directed toward registered nurse (RN) recruitment and retention. If fragmentation of RN recruitment and retention is to be eliminated, innovative programs involving collaboration and use of existing resources will be required. This article provides an overview of how collaboration among nurses, administrators, educators, and a personnel specialist resulted in an upward mobility program for licensed practical nurses (LPNs) to become RNs. While the program is specific to one setting, there are numerous implications for other hospitals confronted with persistent recruitment and retention problems. PMID- 1407081 TI - Surviving the legal hot seat. PMID- 1407082 TI - Facilitating research utilization through collaboration. AB - The rhetorical gap between clinical practice and academia was tested by the development of a special program grant to facilitate use of research by staff nurses. The grant capitalized on an established collaborative relationship between a university school of nursing and a community hospital. The merger of education and practice demonstrated the principles of interinstitutional collaboration in action. Resources of the grant included a doctorally-prepared nurse and a clinical librarian to provide research utilization classes for staff nurses, and an academic credit course to address reality-based practice problems for nurse managers. The model developed for this effort is described and critical behavioral aspects of research utilization for practicing nurses and academic nurses are outlined. PMID- 1407083 TI - Resolution of ethical value conflicts by nurse educators: a pilot study. AB - The literature on ethical conflict resolution in nursing is sparse, but studies concentrating on ethical conflicts in nursing education are rarer still. Lyndaker looks at this emerging area of inquiry and adds her contribution. PMID- 1407084 TI - Successful implementation of case management. AB - Hospitals must critically evaluate all aspects of operations to identify opportunities to cut operating expenses without sacrificing quality of patient care. Many health care organizations are moving toward nurse case management as a possible solution to these concerns. There is a considerable body of literature on the theory and principles of case management, and it is the basis for this article. The purpose of this manuscript, however, is to describe essential factors in the actual application of this theory in building a viable program in a community hospital. PMID- 1407085 TI - Nursing care centers: a collaborative effort. AB - Nursing care centers evolved as a way to deliver health care as well as to bridge the gap between nursing education and nursing practice. This article defines the purposes of a nursing care center, and describes one such center developed by a large Southern university school of nursing, services it renders and the community's need for these services. The importance of collaborative practice in enhancing the success of nursing care centers is discussed. PMID- 1407086 TI - Nurse education legislation: 1935-1992. AB - Most of us cannot remember a time when the feds didn't massively support nursing education. Mahrenholz traces the events that led to what has become our expectation and asks some probing questions about our future needs. PMID- 1407087 TI - [Facial pain due to a lesion in the thorax]. PMID- 1407088 TI - [Sharp increase in the number of deaths due to tobacco in The Netherlands]. PMID- 1407089 TI - [Budgeting of and by family practitioners]. PMID- 1407090 TI - [Medical registries: goal, methods and utilization]. PMID- 1407091 TI - [Decalcification of bone due to corticosteroids]. PMID- 1407092 TI - [The treatment of leg length discrepancy using Phemister's method of epiphysiodesis]. AB - A retrospective study is reported of the results of epiphysiodesis in 67 children. In 47 patients (70%) the final inequality was less than or equal to 1.0 cm. In 9 patients the final inequality was greater than or equal to 1.6 cm. The average leg length inequality could be reduced from 3.2 cm preoperatively to 1.2 cm at maturity. Technical errors were minimal. Failures (9 patients) resulted mainly from problems in timing epiphysiodesis. PMID- 1407093 TI - [Biopsy of potentially malignant bone disorders using an electric minidrill; results of 215 diagnostic drillings]. AB - The results were evaluated of cytological and histological examination of 215 bone biopsies taken with an electric minidrill in 211 patients with suspected malignancies in bones. 171 biopsies were taken in 167 patients with a known malignancy. In 78 cases a malignancy was demonstrated including 4 cases of a second primary malignancy. 44 biopsies of patients without a known primary malignancy resulted in 19 cases of malignancy, mainly metastatic disease. There were no primary bone tumours. Follow-up showed a false negative result in 5 patients, all with known primary malignancies. Follow-up of the patients without known malignancies showed no false negatives. The sensitivity of cytology alone was 92% and the sensitivity of histology alone was 76%. The combination of cytology and histology resulted in a sensitivity of 95%. The specificity of the procedure was 100%. PMID- 1407094 TI - [Distinction between renal and nonrenal hematuria using immunoperoxidase staining of erythrocytes in urine for Tamm-Horsfall protein]. AB - A recently described immunocytochemical staining method to distinguish renal from non-renal haematuria was adapted for use in the standard clinical chemical laboratory. The method is based on the observation that only in case of renal haematuria are erythrocytes in urine coated with so-called Tamm-Horsfall protein, originating from the renal tubuli. Erythrocytes in urine were stained using an indirect immunoperoxidase method, resulting in cells with dark-brown stained surfaces. The staining methods were validated with material from clinically diagnosed cases of haematuria of renal or non-renal origin and compared with scores of the number of dysmorphic erythrocytes, another method to distinguish renal from non-renal haematuria. In specimens of presumed strictly renal haematuria 86% (SD 8.7; n = 26) of the erythrocytes stained immunocytochemically. However, in specimens of haematuria originating from bleeding in the renal pelvis few cells stained (6%; SD 5.8; n = 4). In specimens of purely non-renal haematuria only 13% (SD 13.5; n = 21) stained. Immunocytochemical staining of erythrocytes permitted a much better distinction between renal and non-renal haematuria, with better sensitivity and specificity, than the inspection of erythrocyte morphology. We conclude that immunochemical staining of erythrocytes in urine is a valuable method for distinguishing renal and non-renal haematuria. PMID- 1407095 TI - [Doctor's delay in HIV infection caused by blood transfusion]. AB - Transfusion-associated symptomatic HIV infection in four patients led to death in two patients and to development of serious neurological sequelae in a third patient who also transmitted HIV infection to his spouse. The tardy diagnosis of HIV-associated disease in all cases can be ascribed to ignoring the earlier blood transfusion as a possible cause of HIV infection. This was due partly to advanced age of the patients and partly to lack of familiarity of the attending physicians with HIV-associated problems. This resulted in a substantial doctor's delay. PMID- 1407096 TI - [Ibuprofen meningitis]. AB - A case of aseptic meningitis in an otherwise healthy women aged 47 yr after taking one tablet containing 400 mg ibuprofen is reported. The patient recovered in a few days. PMID- 1407097 TI - [The number of admissions to Dutch hospitals for barbiturate poisoning from 1981 1989 and those for poisoning with sedatives and hypnotics,and benzodiazepines]. AB - Over the period 1981 to 1989, the number of admissions to Dutch general hospitals for barbiturate poisoning has dropped sharply and steadily, due to a more restrictive policy in prescribing regarding these sedatives. This trend is also present concerning poisoning with sedatives and hypnotics in general (ICD-code 967), but not concerning those with benzodiazepines (ICD-code 969.4). The female male ratio was nearly 2:1. This difference is possibly due to the fact that females take more medication than males. PMID- 1407098 TI - [Rheumatoid arthritis and anemia; various aspects concerning prevalence, pathogenesis, diagnosis and therapy]. PMID- 1407099 TI - [Clinically non-functioning hypophyseal adenomas; diagnostic possibilities and therapeutic options]. PMID- 1407100 TI - [Indications for digoxin?]. PMID- 1407101 TI - [Biological psychiatry]. PMID- 1407102 TI - [Hypoglycemia in newborn infants: failing strips]. PMID- 1407103 TI - [Hysteroscopy]. PMID- 1407104 TI - [Tics in Gilles de la Tourette syndrome]. PMID- 1407105 TI - [Digoxin therapy in 24 automated family physician practices]. AB - Since recent insights indicate that most patients with heart failure and a normal cardiac rhythm (HFNR) should not be treated with digitalis, we investigated the treatment policy of general practitioners in this respect. Our descriptive study consisted of a questionnaire followed by a computer based review of patient records of 14 family practices cooperating in the Registration Network of Family Practice (RNFP) and 10 'external' practices. All GPs (n = 51) received the questionnaire on the prescription policy of the GP and cooperating specialists, and on their experience with adverse effects of digitalis therapy. After 2-4 months the GPs of the RNFP (n = 41) received a floppy disc with an algorithm selecting from their problem lists patients with a registered diagnosis of heart failure. The external GPs (n = 10) received an algorithm selecting patients treated with digitalis, since their problem lists were not completely up to date. In all, data of 63,500 patients were examined. On anonymised standard forms, generated by the practice computer, the GPs provided data on the exact diagnosis, medication and adverse effects. Outcome measures of the study were: prescription attitudes (questionnaire) and actual digitalis use (in the selected cases). 33% of the GPs stated that they used digitalis as the preferred therapy of heart failure with normal cardiac rhythm; 30% of the 82 selected HFNR patients had digitalis, while in 42% of the 149 selected patients treated with digitalis a HFNR was registered. Adverse effects had been observed in 3 cases, but could not be excluded retrospectively in 70 cases (49%). Many GPs have not yet adapted their prescription behaviour to recently published insights. Development of a 'digitalis standard in general practice' is recommended. PMID- 1407106 TI - [Observations on the success of worldwide immunization]. PMID- 1407107 TI - [Prevention of harm]. PMID- 1407108 TI - [Revision consensus prevention and treatment of decubitus ulcer]. PMID- 1407109 TI - [The other side of diabetes regulation]. PMID- 1407110 TI - [The Karsten affair and medical professional secrecy]. PMID- 1407111 TI - [Hypoglycemia; is the patient with diabetes mellitus still aware of it?]. PMID- 1407112 TI - [Role of insulin resistance in diabetes mellitus and other risk factors for cardiovascular diseases]. PMID- 1407113 TI - [Consensus on diagnosis, screening and treatment of diabetic retinopathy]. AB - The management and timing of the treatment of diabetic retinopathy has changed in recent years. Screening for diabetic retinopathy should preferably be performed by ophthalmologists. However, in concert with the local ophthalmologist general physicians with knowledge and experience of eye investigations can play a certain part in the screening for diabetic retinopathy. Good communication between general physician and ophthalmologist is of special interest in detecting the risk factors; systemic hypertension, poor metabolic control, pregnancy, proteinuria and rapid metabolic control of previously high blood glucose levels. For the time being fundus photography as a screening method can only be used on a limited scale and under scientific conditions. No consensus could be reached concerning the pre-treatment use of fluorescein angiography. PMID- 1407114 TI - [The treatment of congenital clubfoot in The Netherlands; results of a survey among orthopedic surgeons]. AB - As the result of an inquiry among Dutch orthopaedic surgeons a consensus is formulated on the treatment of congenital talipes equinovarus in the first year of life. From this, the following general directives emerge: Treatment should start early and consist of repeated redressing followed by immobilisation; In more severe cases often surgical release is necessary, this should be performed preferably between the 4th and 9th months of life, in order to make normal motor development possible. PMID- 1407115 TI - [Diabetic patients: no danger on the road]. AB - The evaluation of the risk of traffic accidents among drivers with IDDM and the grounds for excluding them from a driver's license are topical issues, because the E.C. is issuing strict new guidelines. The risk of diabetic patients being involved in traffic accidents as reported in foreign studies and calculated from Dutch data, does not exceed that which is to be expected on account of the prevalence of DM. This justifies a flexible policy for the licensing of drivers with diabetes mellitus. PMID- 1407116 TI - [Type II diabetes mellitus for the family practitioner]. PMID- 1407117 TI - [Current possibilities for the treatment of severe stenosis of the upper airways]. PMID- 1407118 TI - [Lumbar hernia of the nucleus pulposi; not always conservative treatment initially]. PMID- 1407119 TI - [Spasmodic torticollis: a persistent problem]. PMID- 1407121 TI - [Qualified with reservations; the current form of professional protection]. PMID- 1407120 TI - [Population screening for breast cancer: expectations and facts]. PMID- 1407122 TI - [Aminoglycosides once daily: potent but short]. PMID- 1407123 TI - [Indications for cyclosporin in the treatment of idiopathic nephrotic syndrome in adults]. PMID- 1407124 TI - [Indications for the treatment of the elderly with hypertension]. PMID- 1407125 TI - [Initial results with breast screening in the Enschede area. I. Effectiveness]. AB - After one year, the effects of breast cancer screening in the region of Enschede were evaluated by means of seven parameters indicating the long-term health benefits. These parameters were: attendance rate, predictive value of a positive screening test, detection rate, incidence rate, tumour stage, surgical possibilities and type of surgical operations. The results were compared with figures from the national cost-effectiveness analysis. The attendance rate (79%), the predictive value (57%) and the detection rate (0.74%) were well over the national figures of 70%, 41% and 0.64%, respectively. The incidence of breast cancer in the age group 50-69 was 2.5 times higher, as expected. The tumour stage differed significantly (p less than 0.001) from the stages of regularly detected tumours; there was a shift to the lower stages (average tumour size was halved). The surgical possibilities increased significantly (p less than 0.01) and surgical operations performed were mostly less mutilating (not significant). We conclude that the screening for breast cancer in the Enschede region fulfills the criteria of efficacy. It is particularly the combination of a high predictive value and a relatively high detection rate compared with the clinical incidence in the previous years that is indicative of the efficacy. This does not mean that the results prove the long term health benefits of screening for breast cancer. They only give an indication of the future efficacy of screening. The impact on the quality of life is still an open question. PMID- 1407126 TI - [Initial results with breast screening in the Enschede area. II. Efficiency]. AB - The efficiency of breast cancer screening in the Enschede region was evaluated after 18 months on the basis of unfavourable side effects and possible difficulties. These side effects were: 1. for women: psychological burden, period of uncertainty and increasing waiting times; 2. for general practitioners: limited referral; 3. for specialists: increased diagnostics and consultation. The results were compared with the figures derived from the national cost effectiveness analysis. The psychological burden on women with a positive screening result appeared to be considerable, in conjunction with the length of the period of uncertainty. The final result was only known after approximately five weeks when a biopsy was required. In 83 women (41% of all referred women) the overall result of the procedure was false-positive. Occasionally the woman was not referred to a known specialist centre, in contradiction to the guidelines. The increase in the number of diagnostic and therapeutic operations was larger than expected, and is largely accounted for by the radical increase of clinically non-palpable tumours (factor 17). On average, the waiting time for the (first) biopsy was three weeks. A great deal of multi-disciplinary consultation was necessary because of the large increase of non-palpable tumours and in-situ ductal carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407127 TI - [The treatment of children with idiopathic nephrotic syndrome using cyclosporin]. AB - We report our experience with cyclosporine in 14 children with steroid dependent and 7 children with steroid resistant nephrotic syndrome. Cyclosporine was started at a dose of 6 mg/kg/day and was adjusted to maintain a blood level between 60 and 100 ng/ml. 15 patients went into remission with a combined treatment of cyclosporine and prednisone; 9 of these did not have a recurrence following discontinuation of prednisone. In 7 out of these 9 patients cyclosporine was also discontinued, this led in 5 of these 7 patients to a recurrence. Seven out of 14 patients with minimal change nephropathy remained in remission following discontinuation of prednisone and in 4 others the dose of steroid required to maintain remission decreased. In only I out of 4 patients with focal segmental glomerulosclerosis was a remission obtained while in two patients with mesangial proliferation the urine remained protein free during cyclosporine treatment. In 13 patients a repeat biopsy was performed after one year or longer of cyclosporine treatment. Histopathological abnormalities related to cyclosporine were found in 9 patients. In 4 of these severe nephrotoxicity required withdrawal of cyclosporine. Treatment with cyclosporine should be restricted to steroid dependent patients with severe steroid toxicity. PMID- 1407128 TI - [Theo van Gogh's medical record]. AB - In the final months of his life Theo van Gogh was admitted to the 'Geneeskundig Gesticht voor Krankzinnigen te Utrecht'. In November 1990 from the archives of the Willem Arntsz Huis, psychiatric centre in Utrecht, the medical files from this period were made available and a transcription was made by Han van Crimpen and Sjraar van Heugten, scientific collaborators of the Van Gogh Museum. From these data it is acceptable to conclude that Theo van Gogh had dementia paralytica and suffered a fast deterioration of his situation in these last few months. It is, however, probable that at least as early as 1886 Theo showed the first symptoms of this disease when he was in Paris, and that he was treated for this reason by dr. Rivet and dr. Gruby. There are insufficient indications that in Vincent van Gogh's case the same diagnosis can be put forward. It is most probable that during Vincent's visit to Theo in Paris in July 1890 in Theo's case symptoms of his medical deterioration were to be seen and this may have influenced the considerations finally leading to Vincent van Gogh's suicide. PMID- 1407129 TI - [Influenza in the 1991/'92 season; vaccine combination for the 1992/'93 season]. PMID- 1407130 TI - [Can the risk of atrial fibrillation due to pulmonary embolism be minimized by addition of a platelet aggregation inhibitor to an oral anticoagulant?]. PMID- 1407131 TI - [Contact hypersensitivity for corticosteroids]. PMID- 1407132 TI - [Public media and health care]. PMID- 1407133 TI - [The third emancipation]. PMID- 1407134 TI - [Sleeping disorders and drowsiness during the day, a hard to evaluate problem]. PMID- 1407136 TI - [Nomenclature change of bacteria. I. Classification]. PMID- 1407135 TI - [Angiotensin-converting enzyme (ACE) inhibitors in cardiac decompensation; from randomized study to individual patient]. PMID- 1407137 TI - [Nomenclature change of bacteria. II. Nomenclature and identification]. PMID- 1407138 TI - [Expectant management in extrauterine pregnancy is possible]. AB - Twenty-nine patients with presumed ectopic pregnancies, who visited the Onze Lieve Vrouwe Gasthuis outpatient clinic in Amsterdam between January 1990 and July 1991, received expectant management because of mildness of the symptoms. Five patients were shown to have a non-intact intrauterine pregnancy. Only three of the remaining 24 patients needed surgery because of increasing serum HCG concentrations and (or) complaints. Our results therefore indicate that with declining HCG levels and mild symptoms, regardless of the HCG level at presentation, expectant management is justified. PMID- 1407139 TI - [Limited value of routine preoperative laboratory studies in children]. AB - In order to determine whether in routine preoperative laboratory testing of children abnormal results were reported which influenced the course of the anesthesia or of the operation, a retrospective survey of charts was carried out at the University Children's Hospital, Groningen. The patients involved were 143 low risk children, admitted for ENT surgery. The main outcome measures were abnormalities and perioperative complications. There were 1.4% laboratory abnormalities (including five children with a haemoglobin concentration less than 7.1 mmol/l, one with a calcium concentration less than 2.2 mmol/l, one with an albumin concentration less than 30 g/l), and seven complications (bradycardia during intubation, bronchial obstruction, bleeding, excessive vomiting (three times), and leakage of perilymphatic fluid). There were no correlations between the abnormal test results and the complications. Routine laboratory testing in children scheduled for surgery might be reduced to measurement of haemoglobin, especially in non-white children. PMID- 1407140 TI - [Prevalence of HIV in clients of an outpatient clinic for sexually transmissible diseases and in a group of prostitutes and their clients]. AB - In order to gain insight into the heterosexual spread of HIV infections in Amsterdam, a study was carried out in 1991 among persons attending an outpatient clinic for sexually transmitted diseases (STD) and among a group of prostitutes and prostitutes' clients. Out of 2362 persons attending the STD clinic, 2138 (90.5%) could ultimately be examined for presence of HIV antibodies. The HIV seroprevalence was 4.2% (90/2138); among homosexual males it was 22% (70/324), among heterosexual male intravenous drug users 12% (2/17) and among heterosexual males who never had used i.v. drugs 0.5% (5/997). The HIV seroprevalence among female intravenous drug users was 41% (12/29) and that among females who never had used i.v. drugs it was 0.1% (1/771). Among the heterosexually active subjects (active in the preceding six months, including the groups of bisexual males and intravenous drug users), the seroprevalence amounted to 1.5% (28/1884). HIV antibodies could be demonstrated in 1.5% (3/199) of the prostitutes and in 0.5% (1/213) of prostitutes' clients. However, the one positive male had had homosexual contacts in the past. Out of the total of nine heterosexually infected persons, two originated from the Netherlands, two from Ghana, two from Turkey, one from Nigeria, one from Pakistan and one from the Dominican Republic; six of them had commercial contacts. The heterosexual spread of HIV among the heterosexual population of Amsterdam can for the moment be classified as slight. However, further heterosexual transmission of HIV cannot be excluded, considering the frequency of unprotected sex. PMID- 1407141 TI - [Demand for and supply of internists in The Netherlands]. PMID- 1407142 TI - [Me tired? Impossible]. PMID- 1407143 TI - [Me tired? Impossible]. PMID- 1407144 TI - [Me tired? Impossible]. PMID- 1407145 TI - [Me tired? Impossible]. PMID- 1407146 TI - [Me tired? Impossible]. PMID- 1407147 TI - [Postpartum thyroid gland disorders]. PMID- 1407148 TI - [Pregnancy and drug use]. PMID- 1407149 TI - [New macrolides, azalides and streptogramins; current role and their future perspective]. PMID- 1407150 TI - [Physiology and pathophysiology of intrinsic factor secretion and cobalamin (vitamin B12) absorption]. PMID- 1407151 TI - [Diagnosis of infection in full-term infants born after prolonged status of ruptured membranes: clinical observation is sufficient]. AB - We retrospectively studied our strategy in 80 full-term newborns, born more than 24 hours after rupture of amniotic membranes. Six patients developed clinical signs of sepsis, in four of them sepsis was proven by a positive blood culture. In all cases, clinical symptoms were the first sign of infection. Routine laboratory tests (CRP, leucocyte counts and differentiation, thrombocyte counts) and microbiological investigations (surface cultures, cord blood cultures) were not helpful for the diagnosis of infection at an early stage. These findings are in accordance with the literature. We conclude that after prolonged rupture of membranes with full-term newborns postnatal paediatric care can be limited to a close observation period of 48 hours. There is no need for any further routine investigation of infants without clinical signs of infection. PMID- 1407152 TI - [AIDS epidemiology in The Netherlands in persons infected through heterosexual contact]. AB - Ten years after the start of the AIDS epidemic in the Netherlands the proportion of persons infected by heterosexual contacts among the total of AIDS cases diagnosed is small (7.4%). Up to December 1991 the cumulative totals of females and males in the Netherlands reported with the diagnosis and infected by heterosexual contact were 55 and 93, respectively. Of the 55 heterosexual females, 69% had the Dutch nationality, of the 93 heterosexual males, 67%. Considerable proportions of the numbers of AIDS patients in this group (males 47%, females 45%) were diagnosed in the four largest cities (Amsterdam, Rotterdam, The Hague and Utrecht). The remaining cases of AIDS diagnosed in this group were scattered throughout the country. Among heterosexual females a gradual increase of the number of AIDS cases diagnosed was observed since 1985. In the males there was no clear trend in the number of diagnoses since 1984. Of the 55 females, 19 originated from an area endemic for AIDS or had had sexual contacts with a person from such a region (34.6%). Among the 93 males this number was 29 (31.2%). Nineteen of the 55 females (34.6%) were known to have sexual contact with a person from the known risk groups. The same held true of 12 males (12.9%). Of the remaining 17 females (30.9%) and 52 males (55.9%) it was only known that they were heterosexual without further risk factors or risk contacts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407153 TI - [Malignant neuroleptic syndrome: complete anticoagulant treatment or not?]. AB - A case is reported, in which fatal pulmonary embolism complicated the course of a neuroleptic malignant syndrome (NMS). This syndrome includes several risk factors for the development of venous thromboembolism, such as: protracted immobility; severe rigidity causing a slowing of blood flow through the deep venous system; hypovolaemia with increased blood viscosity and activation of coagulation by rhabdomyolysis. An analysis of 115 case reports in the literature on NMS showed that 3 out of 13 patients with fatal NMS (23%) died of pulmonary embolism. The reviewed case, the literature findings and the risk factors mentioned cause us to believe that complete anticoagulant therapy may have a place in the therapeutic approach to patients with NMS. PMID- 1407154 TI - [Medical activities under adverse conditions. Finally: to do or not to do?]. PMID- 1407155 TI - [Cerebrovascular accident]. PMID- 1407156 TI - [Minor symptoms in family medicine; keratitis caused by ultraviolet rays]. PMID- 1407157 TI - [Supply of hearing aids to young children with congenital hearing disorders]. PMID- 1407158 TI - [Neonatal sepsis in the first days of life caused by Haemophilus influenzae]. PMID- 1407159 TI - [Consensus concerning triglycerides and high-density lipoprotein-cholesterol in the United States]. PMID- 1407160 TI - [Transsexualism. I. Description, etiology, management]. PMID- 1407161 TI - [Transsexualism. II. Diagnosis: the initial, tentative phase]. PMID- 1407162 TI - [Transsexualism. III. The second diagnostic phase: the real-life test]. PMID- 1407163 TI - [Transsexualism. IV. Surgical possibilities]. PMID- 1407164 TI - [Abdominal aortic aneurysm as incidental finding in abdominal ultrasonography]. AB - Abdominal aortic aneurysm is a life-threatening condition, which usually remains without symptoms until rupture occurs. The only way to reduce the high mortality rate (estimated at over 80%) is elective surgery on suitable patients. Therefore the presence of such an aneurysm has to be detected. For this ultrasonography is the method of choice. We studied 4399 consecutive patients aged 50 years and older, who underwent abdominal ultrasonography for the first time. According to the recommendation of the Dutch Society for Radiodiagnostics the whole abdomen was screened. In 4026 patients (1717 men and 2309 women) the ultrasound examination was performed for non-vascular reasons. In 199 of these patients (4.9%) an abdominal aortic aneurysm was an adventitious finding (133 men (7.7%) and 66 women (2.9%)). In men aged 60 years and older it was even found in 10.2%. When abdominal ultrasonography is performed for the first time in a patient aged 50 years or older, the aorta has to be screened for presence of an aneurysm. PMID- 1407165 TI - [Screening for familial occurrence of abdominal aortic aneurysm]. AB - To detect familial occurrence of abdominal aortic aneurysms (AAA), the siblings of patients with an AAA were screened by ultrasonography. 128 siblings of 32 patients operated on for AAA were invited. 56 brothers and 52 sisters accepted the invitation. An AAA was diagnosed in 16 brothers (28.6%) and in 3 sisters (5.8%). Six of these siblings were operated on because of an aneurysmal diameter 20 mm in excess of that of the rest of the abdominal aorta, the others were included in a follow-up programme. We conclude that the prevalence of the AAA among brothers is higher in comparison with previously known risk groups and that the family of patients with an AAA are to be considered for screening first. PMID- 1407166 TI - [Psychiatric disorders in elderly patients admitted in a general hospital]. AB - STUDY OBJECTIVE: To determine the prevalence of psychiatric disorders, especially depressive illness, in elderly medical inpatients. SETTING: University Hospital Leiden. DESIGN: Two-stage design. PATIENTS AND METHODS: In six somatic wards a series of 250 patients were randomly selected and screened with two self-rating scales for depression (Beck Depression Inventory, Geriatric Depression Scale) and one screening scale for cognitive dysfunctions (Mini-Mental State Examination). The 52 drop-outs differed significantly from the other patients only in a greater general illness severity, and a higher prevalence of a psychiatric history. Eighty-two patients were selected for a diagnostic procedure with a standardised, semi-structured psychiatric interview, and were classified according to the DSM III-R. Fifty-nine of them were probable cases according to the screening instruments, 23 were selected at random from the probable non-cases. RESULTS: A psychiatric disorder was detected in 25 patients, all but one patient with schizophrenia were found in the group of probable cases. Only five patients were classified as major depression, which lead to a prevalence rate of 2.9% (95% CI 0.4-5.4%). We found evidence of many psychiatric disorders in the group of 52 drop-outs, but these were mostly organic psychiatric disorders, and just one mood disorder. CONCLUSION: The prevalence of major depression is lower than found until now among elderly medical inpatients. PMID- 1407167 TI - [Chorea and primary antiphospholipid syndrome]. AB - Primary antiphospholipid syndrome or PAPS is characterised by antiphospholipid antibodies and arterial and/or venous thromboses. Numerous other clinical features have been shown to be related to this syndrome. Chorea is a well known but rare phenomenon in systemic lupus erythematosus; it has been shown to be strongly related to the presence of antiphospholipid antibodies. We describe two patients with chorea that appeared to be caused by the PAPS. PMID- 1407168 TI - [Promoting work during the sick leave period through cooperation between health insurance physician and the attending physician]. AB - The task of the Dutch social insurance physician is to evaluate claims for disability compensation and to support clients in the process of vocational rehabilitation. Because rehabilitation outcome is associated with length of time out of work, individual rehabilitation plans should be designed at an early stage. Of vital importance in the design of such plans are the client's remaining working capacities. Earlier assessment of functional capacity could be stimulated by more reciprocal consultation and closer collaboration between social insurance and treating physicians. When complete rehabilitation is not yet possible, working shorter hours, if necessary in a different job, could be an initial solution. As a result the client keeps in touch with the working environment and also a clearer picture is provided of what he or she is still capable of doing. Besides, the influx into the disability law system, which automatically follows if the non-working period exceeds 1 year, with its serious financial, social and emotional effects for the client, may be reduced. PMID- 1407169 TI - [Severe psychological side effects in children using high-dosage deptropine]. PMID- 1407170 TI - [Severe psychological side effects in children using high-dosage deptropine]. PMID- 1407171 TI - [Severe psychological side effect in children using high-dosage detropine]. PMID- 1407172 TI - [Invagination: the importance of early diagnosis]. PMID- 1407173 TI - [Postasphyxial encephalopathy in newborn infants following administration of nalbuphine during childbirth]. PMID- 1407174 TI - [Crib death and promethazine]. PMID- 1407175 TI - [Immunotoxicity and pathogenicity of substances]. PMID- 1407176 TI - [Choice of time of surgery in the surgical rehabilitation of Graves' ophthalmopathy]. PMID- 1407177 TI - [Sleeping together and safety of the infant]. PMID- 1407178 TI - [Malaria prevention]. PMID- 1407179 TI - [The treatment of malaria]. PMID- 1407180 TI - [Influenza vaccination and Postal Box 51-campaign]. PMID- 1407181 TI - [Surgical rehabilitation in patients with Graves' ophthalmopathy; favorable results of orbital decompression via coronal approach]. AB - Bilateral decompression of the orbit by a coronal approach was performed for cosmetic rehabilitation in 53 female patients with proptosis in the non inflammatory stage after Graves' ophthalmopathy. Proptosis reduction averaged 5.9 mm Hertel value one year after surgery. All patients were satisfied with the cosmetic result obtained. Advantages of the technique used are: good access to all orbital walls facilitating adequate proptosis reduction; no visible scars after surgery; only very few complications. In our group there was no loss of visual acuity and the incidence of diplopia after surgery of only 4% is the lowest reported in the literature. PMID- 1407182 TI - [Favorable results of the surgical treatment of intra-articular crush fractures of the distal femur]. AB - Severely comminuted intra-articular femoral fractures are usually associated with major soft-tissue damage as a part of serious multiple injuries. Surgical treatment should aim at exact anatomical restoration of the articular surface. Internal fixation should be stable so that functional after-treatment is possible, a condition of achieving an optimal result. In a period of over 7 years, 24 patients with 26 intra-articular comminuted fractures were operated on. Twenty patients had multiple injuries (ISS > 18), 11 fractures were complicated. Postoperatively, impaired wound healing occurred in three elderly patients; in two of these amputation was necessary. Considering the severity of the injury, the long-term results were good: ten of the 16 patients examined with 18 fractures recovered completely, in the other cases the functional result wa adequate to good. Surgical treatment of comminuted intra-articular fractures of the distal femur is to be adapted to the individual case; depending on the fracture type and the associated damage a selection is to be made from various implants and techniques. With consistent, individually adapted application of the current AO techniques good results can be obtained. PMID- 1407183 TI - [Quantification of the gnostic sensitivity via measurement of the vibration threshold and of finger tip sensation]. AB - OBJECTIVE: Quantification of vibration perception and fingertip sensation in routine neurological examination. SETTING: Neurological Clinic, University Hospital, Groningen, the Netherlands. DESIGN: Prospective, controlled investigation. METHODS: Vibration perception and fingertip sensation were quantified in a large group of normal control persons of various ages and in neurological patients and compared with the usual sensory tests at routine neurological examination. The vibration perception limit was measured with a biothesiometer without accelerometer, the fingertip sensation with a device for two-point discrimination slightly modified according to Renfrew ('Renfrew meter'). Concordance of the tests was studied by calculating kappa values. RESULTS: The normal values of both sensory qualities had a log-normal distribution and increased with age. The values obtained with the Renfrew meter correlated well with those of the two-point discrimination and stereognosis but were systematically higher than those indicated by Renfrew. CONCLUSION: Both methods appear useful at routine neurological examination if certain measuring precautions are taken. PMID- 1407184 TI - [The phenomenon of the delayed initial attack of tertian malaria]. AB - From 1986 to 1990 we have treated 215 patients with falciparum malaria. In 8 patients (4%) who had not returned to any malarial area, malaria attacks recurred after 6-20 weeks. Curiously these were now caused by different species: Plasmodium vivax (4 patients) and P. ovale (4 patients). After proper management of malignant tertian malaria caused by P. falciparum, patients are considered cured, provided the treatment has been in accordance with the resistance pattern of the parasite in the country of origin. Yet, in a small number of patients attacks of malaria recur after different time intervals. The explanation of this seemingly paradoxical phenomenon is that these were delayed primary attacks of benign tertian malaria rather than recrudescences of malignant tertian malaria. Consequently the patients must have been infected by two different species of malaria at a time. In P. vivax and P. ovale hypnozoites occur (notably absent in P. falciparum), dormant stages in the liver that are not susceptible to the antimalarials in use for the eradication or prophylaxis of the blood stages which cause the acute attacks of malaria. After a variable amount of time the blood is then (re)invaded and the patient suffers a delayed primary attack or a relapse. Physicians should be aware that definite cure of malignant tertian malaria does not prevent future attacks of benign tertian malaria. They should inform their patients accordingly. PMID- 1407185 TI - [Doctor's delay in HIV infection caused by blood transfusion]. PMID- 1407186 TI - [Budgeting of and by family practices]. PMID- 1407187 TI - [The spectrum of acute meningococcal disease]. PMID- 1407188 TI - [Life's end in a nursing home]. PMID- 1407190 TI - [Surfactant therapy in respiratory distress syndrome; a review]. PMID- 1407189 TI - [Bacterial meningitis; pathogenesis and current possibilities of additional therapy]. PMID- 1407191 TI - [Age in neonatal screening and birth weight]. PMID- 1407192 TI - [Cause of death in nursing homes]. AB - Data from the Verpleeghuis Informatie Systeem (Nursing Home Information System, SIVIS) of the Stichting Informatiecentrum Gezondheidszorg (Foundation Information Centre Public Health, SIG) unlike data from the Central Bureau voor de Statistiek (Central Statistics Office, CBS) can afford insight into the primary causes of death of patients in Dutch nursing homes. We studied the question whether the causes of death of patients in somatic and psychogeriatric care differed and whether in these groups there was difference between those decreased within and after six months. Also, using the death certificates issued for the 29 patients deceased in nursing home De Bieslandhof in the first quarter of 1991, a comparison was made of reporting to the SIG and to the CBS. In 1989, data on 82.5% of the nursing home patients were registered in the SIVIS. Irrespective of the interval between admission and death and the nature of the multidisciplinary care (somatic or psychogeriatric), pneumonia was the cause of death most frequently stated (16%). Of the somatic patients decreased within six months the cause of death was mostly a malignancy. The psychogeriatric patients mostly died due to dehydration and cachexia. However, uncertainties in establishing the primary cause of death and registration errors are not made sufficiently clear in the SIVIS registration. The reporting to SIG and CBS does not always tally. PMID- 1407193 TI - [Prevention and treatment of respiratory distress syndrome in premature infants using intratracheally administered surfactants]. AB - OBJECTIVE: To study the effects of administration of surfactant immediately after birth (prophylactic) or after 6 hr (therapeutic) to 81 Dutch preterm infants from a multicentre trial. SETTING: University Hospital Leiden and Sint Joseph Hospital, Veldhoven. DESIGN: A randomized controlled trial with stratification for biochemical lung (im)maturity. The aims of the study were (I): to improve the TcPO2/FiO2 ratio by 40% and (2) to prevent the respiratory distress syndrome by 50% at 6 hours after birth. The secondary goal was to compare effects of prophylactic versus therapeutic use of exogenous surfactant (from 6 hours onwards) in surfactant-deficient infants. PATIENTS: The entrance criteria of the study were: (I) inborn children with a gestational age between 26 and 30 weeks, (2) elective intubation and (3) sampling of bronchotracheal or gastric aspirate. After randomization the children received surfactant within 10 minutes after birth prophylactically (n = 42) or 6 hours after birth if they needed more than 60% oxygen (13 of 39 control infants). A second dose of surfactant was given if, at 6 hours after the first dose, the FiO2 was still high (> or = 0.6). TREATMENT: We used a natural porcine surfactant preparation (Curosurf) in a dose of 200 mg/kg given through the endotracheal tube. RESULTS: The mean gestational age of the 81 infants was 28.2 weeks. The TcPO2/FiO2 ratios increased in the prophylactic group compared with the controls (38 versus 30 kPa; p < 0.05). RDS occurred less often and less severely in the prophylactic group (p < 0.05). Neonatal mortality was lower in the prophylactically treated infants (3/42) than in the control group (10/39; p < 0.05). Compared with the control infants with immature lungs, the immature prophylactically treated infants had six hours after birth higher TcPO2/FiO2 ratios (35 vs 13 kPa; p < 0.001), a 35% reduction of the incidence of RDS with a significant reduction of its severity (p < 0.05), and significantly lower mean airway pressures (0.87 versus 1.24 kPa; p < 0.005). The surfactant given 6 hours after birth to the immature controls resulted in an immediate improvement of the oxygenation. Nevertheless, these infants spent more time on the respirator and needed extra oxygen for longer periods than the immature infants prophylactically treated (p < 0.05). CONCLUSION: Surfactant, given either prophylactically or therapeutically, results in clinical improvement of children with biochemically immature lungs. A prophylactic treatment, moreover, results in reduced incidence and severity of RDS, in a significant shortening of the time spent on the respirator and in reduced need of extra oxygen compared with therapeutic treatment. We recommend to give surfactant prophylactically or at the first signs of RDS. PMID- 1407194 TI - [Diagnosis in recurrent bacterial meningitis; a literature study]. AB - Recurrent bacterial meningitis can be caused by different mechanisms. In order to make the diagnostics more efficient, we studied literature to find these underlying mechanisms. Two groups could be identified: group I, patients with a congenital or posttraumatic defect in the bones of the skull and group II, patients with a deficiency of a component of complement. The patients in group I were much younger at the time of their first meningitis and suffered more often from otitis, rhinorrhoea and deafness diagnosed before the first meningitis. Streptococcus pneumoniae was most frequently cultured in the cerebrospinal fluid, the group with complement deficiency showed Neisseria meningitidis almost exclusively. Family history revealed more members with infections caused by neisseriae spp. Although it was difficult to diagnose the bony defects, physical examination, radiography and high resolution CT scanning of the skull were helpful. Age, history, physical examination and cerebrospinal fluid culture were the most helpful in diagnostic factors. PMID- 1407196 TI - [Morbidity and results of 100 radical hysterectomies performed in an oncology center]. PMID- 1407195 TI - [Pain in the forefoot: a support sole is no panacea]. AB - Three case histories of a painful forefoot due to an uncommon disease are given: Freiberg's disease, Morton's neuroma and metatarsal stress fracture. The differential diagnosis of metatarsalgia should include these diseases, especially if no static deformities are found. PMID- 1407197 TI - [Facial pain in a thoracic disease]. PMID- 1407198 TI - [Facial pain in a thoracic disease]. PMID- 1407199 TI - [Control of the resistance problem by managing an antibiotic protocol]. PMID- 1407200 TI - [Chronic fatigue syndrome]. PMID- 1407201 TI - [Prevention and treatment of osteoporosis]. PMID- 1407202 TI - [Prevention and control of pain in (adeno)tonsillectomy]. PMID- 1407203 TI - [Prevention and control of pain in (adeno)tonsillectomy]. PMID- 1407204 TI - [The prevention of recurrent erysipelas]. PMID- 1407205 TI - [Treatment of varicella with acyclovir in children with normal immune defense?]. PMID- 1407206 TI - [Lupus erythematosus; current treatment methods]. PMID- 1407207 TI - [Teratogenic risks of high-dosage vitamin A]. PMID- 1407208 TI - [Current guidelines for gynecological examination in DES daughters]. PMID- 1407210 TI - [Ischemic hepatitis]. AB - Triggered by a case of ischaemic hepatitis (shock liver) in a patient with severe respiratory insufficiency, we tried to gather information about clinical characteristics and incidence. To our surprise, this information could be found neither in major critical care, medical or gastroenterology textbooks nor in textbook indices or works on differential diagnosis. From Sept. 1989 to May 1990 we studied all possible cases of ischaemic hepatitis in a 390 bed general hospital, to establish incidence. Using computerised data from the clinical chemistry laboratory, all patients with grossly abnormal liver function tests were identified. In this nine-month period 27 adult patients had a peak ALAT level of > 500 U/l: 8 of these suffered from ischaemic hepatitis, using the criteria described by Gibson et al. In another 5 this diagnosis was suspected but could not be ascertained before death (30% and 18% of all cases). In all these cases ASAT, ALAT, LDH levels were 8-100 times normal, but bilirubin, alkaline phosphatase, gamma-glutamyl transferase and prothrombin time were only slightly abnormal. With correction of the underlying disorder enzyme levels returned to normal very rapidly, in 5-10 days. Ischaemic hepatitis could easily be distinguished from other causes such as alcoholic, viral or drug-induced hepatitis. Ischaemic hepatitis was the most frequent cause of severely elevated ASAT, ALAT and LDH in hospitalised patients. The diagnosis can easily be made on clinical characteristics and the typical biochemical pattern. An elaborate work up or invasive procedure is redundant. Prognosis per se is excellent but depends on the underlying disorder. PMID- 1407209 TI - [Are the long-term results of venous aortocoronary bypass procedures really so bad? A prospective 13-year-long study of 428 patients]. AB - OBJECTIVE: To assess the long-term results of coronary surgery using venous bypasses. DESIGN: Prospective study. SETTING: St. Antonius Hospital, Nieuwegein, the Netherlands. METHOD: In 446 successive patients subjected to coronary surgery between 1 April 1976 and 1 April 1977, a complete long-term follow-up study was carried out after an average of 11.5 years (1.5 months-14.3 years). RESULTS: The peroperative mortality was 3%, a peroperative myocardial infarction occurred in 6.3% and complete revascularization was achieved in 77.6% of the patients. In 90 of 100 patients selected at random, cardiac catheterization was performed 13.5 months on average after the operation. The patency of the single grafts was 89.8%, that of the side-to-side and end-to-side anastomoses of the sequential grafts was 90.4% and 83%, respectively. Mortality, myocardial infarction, necessity of a second operation and angina pectoris occurred with low frequency during the first five years after the operation. Subsequently, complications increasingly occurred. Ten years after the operation 18.8% of the patients had died, 11.9% had suffered a myocardial infarction, 13.4% had been subjected to a second operation and 6.4% to balloon angioplasty, while 46.4% had once more developed angina pectoris. Thirteen years after the operation 29% of the patients had remained completely free from cardiac problems. CONCLUSION: Although arterial bypasses have been increasingly used in recent years, an indication for the use of venous transplants will continue to exist in the future, also, for certain groups of patients (those younger than 50 or older than 75 years). Our study clearly shows that with venous bypasses, also, satisfactory long-term results can be obtained. PMID- 1407211 TI - [Disseminated lupus erythematosus induced by carbamazepine (Tegretol)]. AB - A 20-year-old man is described with drug-induced lupus erythematosus (DILE) induced by carbamazepine prescribed for epilepsy. The symptoms consisted mainly of arthritis and largely disappeared when carbamazepine was replaced by oxcarbazepine. With a simple decision scheme based on serological findings, differentiation between (idiopathic) systemic lupus erythematosus and DILE is possible. PMID- 1407212 TI - [The bill medical experiments]. PMID- 1407213 TI - Traditional practice builders. PMID- 1407214 TI - Advances in hospital infection control programs. AB - The past decade in infection control has seen remarkable growth of both practitioners and the basic infection control program. Technical advances led to more sophisticated data collection, analysis, and strategies. Health care is being streamlined to be highly effective and efficient. It is easy to become enchanted with new, exciting, and high-tech aspects of disease prevention and control, but we must all remember that the basics of a good program from 10 years ago are still applicable today. PMID- 1407215 TI - Surfactant. PMID- 1407216 TI - Health USA: appropriate for Nebraska (a commentary). PMID- 1407217 TI - Airway obstruction following transhiatal esophagogastrectomy. AB - A 79 year old man suffered acute respiratory distress secondary to delayed gastric emptying several months following esophagogastrostomy. No drainage procedure was performed at the time of the procedure. The need for a drainage procedure is controversial. Symptoms of gastric stasis have reportedly improved with a drainage procedure and the risk of concomitant pyloromyotomy or pyloroplasty has been shown to be minimal and may prevent a potentially catastrophic complication as described in this report. PMID- 1407218 TI - High frequency jet ventilation for respiratory failure in newborn infants. PMID- 1407219 TI - Effects of AIDS, cocaine, and family violence on children in out of home care. AB - The medical practitioner encounters more medical and psychological illness in foster children than in the general population. The number and complexity of problems in foster children and their families has been increased by acquired immunodeficiency syndrome, cocaine, and family violence. Clinicians who are aware of the high rate of chronic medical problems in foster children will be prepared to diagnose, treat, and coordinate care and follow-up. It is helpful to understand the vulnerability of foster children to emotional disturbance both as a result of family dysfunction which necessitated placement and as a morbidity of the psychological stress of the crisis of placement with subsequent risk of deterioration in foster care. Practitioners' formal knowledge of the problems of foster children and of the structure of the child welfare system promotes appropriate patient care and better directed advocacy. PMID- 1407220 TI - Acute and chronic effects of hypoglycemia on cognitive and psychomotor performance. AB - The acute and chronic effects of hypoglycemia on cognitive and psychomotor performance are reviewed. Studies involving pediatric and adult subjects, both with and without diabetes were evaluated. The preponderance of studies suggest that hypoglycemia can be an unintended yet frequent result of treatment of patients with IDDM. Significant cognitive and psychomotor deficits were reported even with mild episodes of hypoglycemia. Early age of diabetes onset and frequent episodes of hypoglycemia were found to be highly related to significant deficits in intellectual and academic performance. Patients evidencing performance deficits did not always report symptoms of hypoglycemia. Recovery of cognitive functioning lagged restoration of euglycemia but typically returned to baseline levels of performance. Recommendations for improved patient care are provided. PMID- 1407221 TI - Amniocentesis: indications. PMID- 1407222 TI - [Psychotherapy research and therapeutic management]. AB - The history of psychotherapy research has been closely allied with the development of clinical practice, as this review demonstrates. Empirical psychotherapy research aims at the scientific evaluation of existing practice and at the discovery of new fields of application. The early phases of psychotherapy research were concerned with scientific justification and societal legitimation. These questions changed with the extension of possible indications, the growing differentiation of treatment procedures and the progressive implementation of psychotherapy within the health-care system. The early issue "does psychotherapy work at all?" has been replaced by the questions "to whom is psychotherapy helpful?" and "how does psychotherapy work?". As an established part of the health-care system, psychotherapy is now faced with the same urgent problems as other medical specialties: therapeutic goals and economic conditions have to be brought in balance. Thus the perspectives of psychotherapy research have to encompass the individual patient as well as the system of care. These demands create new questions which enlarge the approaches of traditional psychotherapy research; new structural and logistic methodologies are asked for. We conclude by referring to a multicenter study on the psychodynamic treatment of eating disorders that has been initiated by the Center for Psychotherapy Research in Stuttgart as a prototype form of the new look in psychotherapy research. PMID- 1407223 TI - [Conversion symptoms of patients in psychiatric liaison care]. AB - At the consultation-psychiatric service of a large university hospital conversion disorders present ca. 50% of the "somatoform disorders". The rate of incidence of conversion disorders was 4% of all patients seen in the service, i.e. 20-30 referrals per annum. A report on 103 patients referred during 1987-1990 is given concerning basic sociodemographic data, symptom clusters, course of illness, age at onset of the disorder, psychiatric and family history, psychosocial conditions and intrapsychic conflicts, additional affective disorders and psychophysiological symptoms, illness behaviour, cognitive attitudes towards illness. The rate of 35% patients showing an underlying somatic disorder in addition to their conversion symptoms had to be appreciated. Possible relations of conversion disorders to affective illness, somatization disorder and neurologic disease had to be discussed as to course of illness and theoretical concepts. PMID- 1407224 TI - [Psychopathologic findings and results of treatment of pension applicants]. AB - As part of a broader follow-up study (n = 1088) in a psychosomatic hospital, 35 patients who had applied for early retirement on health grounds were examined by means of a psychosomatic personality inventory (PSKB-Rudolf). In addition to confirming previous findings in relation to the character-profile and defence mechanisms of such patients, the present study describes a cluster of characteristics that would lead to unfavourable therapeutic results. The fact that these persons had applied for early retirement had in itself no appreciable therapeutic consequences. PMID- 1407226 TI - [Dementia diseases and minor cognitive impairments in elderly patients in general practice. Results of a cross-sectional study]. AB - General practitioners in 24 Mannheim practices kept a record of all over-65-year old patients seen during four weeks (n = 3,737), and made ratings of their cognitive functioning with the help of simple guidelines. For a sub-sample of patients (n = 407), these ratings could be compared with assessments made by the research team, on the basis of a standardized interview and test procedure (Hierarchic Dementia Scale). The research data indicate that 8% of the patients manifested clinical dementia, a further 8% so-called 'mild dementia' and 17% milder, non-disabling degrees of cognitive impairment. The proportion of affected persons in each of the groups rises steeply with increasing age above 65 yr. The ability of the practitioners to detect dementia--including the milder degrees- among their elderly patients exceeded expectation (sensitivity 92%; specificity 76%). The test-score profiles of the patients, grouped according to their own doctors' ratings, conformed to clinical concepts of the progressive course ('staging') of dementing illness, while the degree of disability in everyday life, and dependency on others, also increased steeply across the groups. These findings emphasize the importance of general medical practice for the early detection of dementia in the elderly population, and potentially also for case management. PMID- 1407225 TI - [Recognition of emotions in facial expression of visual half-field images by schizophrenic and depressed patients]. AB - Twenty schizophrenics, 20 depressives, and 20 normal controls were asked to identify positive and negative emotional expressions of faces tachistoscopically presented to the left and/or right visual hemifields. Results replicated the frequently cited recognition advantage for emotional stimuli presented in the left visual hemifield (right hemispheric processing). A significant reduction in decoding advantage was observed in both patient groups, which could be explained in terms of an interhemispheric disconnection syndrome in schizophrenics and depressives. Bilateral findings in particular tend to support this hypothesis, since they revealed that both cerebral hemispheres processed contrary information simultaneously. PMID- 1407227 TI - [Symptom severity and symptom progression in Alzheimer's disease-- comparison between two cases with early and late onset]. AB - Since the first description of Alzheimer's disease rapid symptom progression and relatively severe cognitive symptoms have been frequently associated with early onset age, while slow symptom progression and relatively mild cognitive symptoms were often related to late onset age. In a longitudinal study of 90 patients with mild to moderate Alzheimer's disease we investigated these hypotheses. We found that neither severity of cognitive symptoms nor symptom progression in Alzheimer's disease were associated with onset age. In addition, a comparison of extreme groups (group 1: less than 60 years of age; group 2: greater than 75 years of age), taken from the study sample, showed similar results with respect to the independent variables. The results of this study suggest that the interindividual variability of cognitive impairment as well as the large variation of symptom progression in Alzheimer's disease cannot be explained by onset age. PMID- 1407228 TI - [Organic correlates of depressive symptoms in Alzheimer's dementia. Results of a prospective study, review of the literature]. AB - The diagnosis of Alzheimer's disease (AD) was verified at post-mortem examination in 46 patients (9 male: 37 female; mean age 83.6 +/- 6.5 years) from a prospective clinical study. Compared to 10 age-matched controls, the total AD group showed a significant neuronal loss in the locus coeruleus, dorsal raphe nucleus, substantia nigra and in the basal nucleus of Meynert. Twelve patients (1 male: 11 female) had experienced symptoms of depression. These patients had significantly lower neuronal counts in the locus coeruleus, but less severe cell loss in the basal nucleus of Meynert compared to the AD patients without depression. PMID- 1407230 TI - [Selegine in Parkinson's disease--current status in research and therapy. 2nd Internation Congress of Movement Disorders. Munich, 23 June 1992]. PMID- 1407229 TI - [Pharmacotoxic psychosis and extrapyramidal motor syndrome. A case of acute adverse effect of fluoxetine and flupenthixol]. PMID- 1407231 TI - [Hemodilution in the therapeutic overall plan in acute cerebral ischemia]. PMID- 1407232 TI - Dutch Society of Gastroenterology and Dutch Society of Hepatology meeting. 19-20 March 1992. Abstracts. PMID- 1407233 TI - Endocarditis prophylaxis. PMID- 1407234 TI - Ursodeoxycholic acid treatment in primary biliary cirrhosis with the emphasis on late stage disease. AB - We studied the effect of ursodeoxycholic acid in 19 patients with primary biliary cirrhosis, mainly stages III and IV. The dose of UDCA employed was 10-15 mg/kg body weight per day. After 1 yr, 17 patients were still using UDCA, and the mean values of serum alkaline phosphatase, gamma-glutamyltranspeptidase and alanine aminotransferase had fallen significantly. Serum bilirubin, initially elevated in 7 of the 13 late-stage (III and IV) patients, showed a further increase in 3 of the 7 patients. In 2 of these 3 patients, UDCA had to be withdrawn (dose reduction had no effect). One patient developed a decompensated cirrhosis in spite of UDCA withdrawal. Pruritus worsened in 4 patients, all of whom were late stage patients. Ten late-stage (III-IV) patients showed improvement in liver biochemistry and clinical findings as did all early-stage PBC patients. Thus, UDCA treatment is not beneficial for all PBC patients. Special care should be taken in the early phase of UDCA therapy in later-stage (III-IV) patients: frequent biochemical checks should be carried out, for instance every 2 weeks in the first 2 months after starting UDCA, especially the estimation of bilirubin. PMID- 1407235 TI - Additive value of transoesophageal echocardiography in the visualization of carcinoid heart disease. AB - A 65-yr-old woman with atypical complaints and a tricuspid insufficiency murmur underwent transthoracic echocardiography, which showed right-sided abnormalities, but did not allow clear visualization of the valves. Subsequent transoesophageal imaging, however, raised the suspicion of carcinoid heart disease, because of the typical lesions. The diagnosis was thereafter confirmed by biochemical investigations, scintigraphy and abdominal ultrasound. This case suggests that transoesophageal echocardiography may have additive value in the detection of carcinoid heart disease. PMID- 1407236 TI - Pyrexia of unknown origin as the only manifestation of colorectal carcinoma. AB - Patients with colon cancer rarely present with pyrexia of unknown origin (PUO) without other manifestations or symptoms. The present paper reports a patient who presented with a 6-month history of fever. The patient was found to suffer from well-differentiated adenocarcinoma of the sigmoid colon. A few days after sigmoidectomy the fever subsided and the patient recovered. Investigation of the large bowel should always form part of the evaluation in patients with pyrexia of unknown origin. PMID- 1407237 TI - Malabsorption due to a ventral hernia. AB - A case of malabsorption due to a stagnant loop which occurred in a huge ventral hernia is presented. The clinical course was relatively indolent with symptoms of malabsorption and occasional abdominal pain. Although rare, abdominal hernia can lead to malabsorption due to bacterial overgrowth as a result of stagnant loop. PMID- 1407238 TI - Growth hormone and insulin-dependent diabetes mellitus. PMID- 1407239 TI - Mortality and causes of death after hip fractures in The Netherlands. AB - The mortality rate and causes of death after a hip fracture were studied in 493 consecutive patients with a hip fracture. All patients were treated in three hospitals in Utrecht, The Netherlands. The mortality rate following hip fractures is high and age dependent. Forty-five patients, 38 women and 7 men, died during the period of hospitalization (9.1%). One year after the date of hip fracture 23.6% of the women had died and 33.0% of the men. Four years after the date of hip fracture the mortality rates in women and men were 44.4% and 55.3%, respectively. Male sex, concomitant illnesses and in-hospital complications are negative determinants of survival. The in-hospital mortality was due to: cerebrovascular accident (n = 7), cardiac decompensation (n = 12), myocardial infarction (n = 4), pulmonary infection (n = 6), intestinal bleeding (n = 1) and sepsis (n = 5). From the registration of death causes we learned that 54 deaths were directly due to the hip fracture, 4 due to bed sores, 34 due to infectious diseases, 62 due to cardiovascular disease, 22 due to cerebrovascular accidents, 14 due to diabetes mellitus, and 33 due to neoplasm. The high mortality rate within the first 8 weeks after the date of hip fracture was mainly attributed to the hip fracture. PMID- 1407240 TI - Does baseline serum total calcium level influence the blood pressure response to calcium supplementation? A double-blind study. AB - This was a randomized and double-blind study to examine: (1) the effect of a 1500 mg/day calcium supplement vs a placebo for 8 wk in 42 adults with high normal or mildly elevated blood pressure (BP) and, (2) the relationship between baseline serum total calcium levels and BP response to calcium supplementation. Following the experimental protocol, mean pressures were lower in the treatment vs placebo group (95.7 mmHg and 102.1 mmHg, p = 0.002), but response was not related to initial serum total calcium levels. After 8 wk of calcium supplementation, serum total calcium was greater in the treatment group compared to the placebo group (p = 0.02). Within the treatment group only, the change in total serum calcium was related to the change in parathyroid hormone (r = -0.92, p = 0.0002); and the change in ionized calcium was related to the change in parathyroid hormone (r = 0.68, p = 0.03) in the subgroup with low baseline serum total calcium. This study provides further support for the hypotensive effect of supplemental calcium in some people. However, it fails to clarify or expand upon previous reports that a low serum total calcium level might be predictive of the blood pressure response to increased calcium. PMID- 1407241 TI - Inhibitors of recombinant human erythropoietin in chronic renal failure. AB - This study investigates which factors influence the response of administered recombinant human erythropoietin (Re-HuEPO) with respect to the increase of haemoglobin in patients with end-stage renal disease. Pharmacokinetic parameters of administered Re-HuEPO in patients with end-stage renal disease and considerable differences in the amount of Re-HuEPO required ("Re-HuEPO-need") to obtain an increase of haemoglobin, revealed a pattern of dose-dependent first order elimination without significant interindividual differences between the patients. As variable immunological inhibitors of erythropoietin are also absent, the administered Re-HuEPO seems to be equally available to the erythron in the various patients. In vitro incubation experiments with bone marrow cells show that the sera from patients with end-stage renal disease contain inhibitors of the erythropoietin-induced stimulation of bone marrow cells. As the patients' sera differ with regard to the degree of inhibition of erythropoietin bioactivity, this inhibition may also be responsible for the interindividual differences in amount of erythropoietin required. Besides a reduced endogenous production of erythropoietin, these inhibitors of the bioactivity of erythropoietin may also contribute to the pathogenesis of anaemia in patients with chronic renal failure. PMID- 1407242 TI - Chronic lymphocytic leukaemia presenting as renal failure with lymphocytic infiltration of the kidneys. AB - A case of renal failure is reported in a 60-yr-old male as the first clinical manifestation of chronic lymphocytic leukaemia (CLL). It appeared to be due to a massive interstitial infiltration of both kidneys by small lymphocytes. Combination chemotherapy consisting of monthly courses of cyclophosphamide, vincristine and prednisone (COP), resulted in a rapid improvement of the renal function and in an apparent haematological and clinical remission of the CLL. After six courses, the COP therapy was stopped and replaced by a maintenance treatment with oral chlorambucil. During follow up, now lasting more than 3 years, no deterioration of renal function has been noted. PMID- 1407243 TI - Pancreatitis induced by mesalamine. AB - Sulphasalazine is an active agent in the treatment of chronic inflammatory bowel disease, but there are a number of well-known side effects, including pancreatitis. The newer 5-ASA agents are thought to be equally effective but less toxic. Here we describe a patient who developed a pancreatitis due to mesalamine; this was confirmed at rechallenge. PMID- 1407244 TI - Chronic airflow obstruction, hyperinflation and the respiratory muscles. PMID- 1407245 TI - Biological action of pancreatic amylin: relationship with glucose metabolism, diabetes, obesity and calcium metabolism. AB - Amylin, also called islet amyloid polypeptide (IAPP), or diabetes-associated peptide (DAP) is a recently discovered 37 amino acid polypeptide which has been shown to be co-secreted with insulin from the pancreatic beta-cell. The peptide turned out to be the major constituent of pancreatic amyloid deposits which are frequently found in the pancreas of type II diabetic patients. Therefore, a role for amylin in the aetiology of type II diabetes was hypothesized. To investigate this possibility, several studies have been performed to elucidate whether amylin is able to impair insulin secretion and action, two characteristic features of type II diabetes mellitus. These studies suggest that it is unlikely that amylin has a direct inhibitory effect on insulin secretion. Amyloid deposits, however, which are derived from the in situ polymerization and precipitation of amylin, may impair beta-cell function during type II diabetes by damaging and covering beta-cells. Furthermore, it has been shown that amylin has the potential to antagonize the action of insulin on glucose metabolism by increasing hepatic glucose production and by decreasing muscle, but not adipocyte glucose uptake. For these reasons, it has been suggested that amylin might be involved in the pathophysiology of type II diabetes and obesity, disease states which are characterized by abnormal beta-cell function and insulin resistance. In addition, amylin was shown to induce hypocalcaemia by inhibiting osteoclast-mediated bone resorption in a calcitonin-like manner. Therefore, amylin is likely to be involved in both the modulation of glucose and calcium metabolism. PMID- 1407246 TI - Parkinson's disease in Taiwan: an analysis of 215 patients. AB - 215 Chinese Parkinson's disease (PD) patients on levodopa therapy were followed up between 1982 and 1991. The ratio of males to females was 2.4 to 1. The mean durations from onset of the illness to stages I and II of Hoehn and Yahr (mild disability) were 4.0 and 6.5 years, to stage III (moderate) 7.9 years, and to stages IV and V (severe) 9.8 and 11.8 years. The mean duration of illness for living patients was 8.6 years. The mean duration of illness before death for the 46 patients who died was 8.9 years. The mean age at death was 68 years (4.4 years less than the normal life expectancy in Taiwan). The fate of this disease showed that patients with unilateral symptoms initially had a better prognosis than those with bilateral symptoms. The symptoms at onset were unilateral in 70% of the patients, of whom 91% had a spread of symptoms to the opposite side after a mean of 3.4 years. Familial PD occurred in 2.8% of our patients. The occurrence of blood ABO groups was not significantly different between the PD patients and the general population of Taiwan. Our findings differed from those in Western series by having a predominance of males, and a relatively shorter duration of unilateral symptoms before spread to the opposite side. In addition, the duration of illness and the survival time under levodopa treatment were shorter in Taiwanese and Japanese than in Western series. PMID- 1407247 TI - Survival in presenile Alzheimer's and multi-infarct dementias. AB - Duration of survival in patients who had died of presenile Alzheimer's disease (AD) or presenile multi-infarct dementia (MID) in 13 mental hospitals in Scotland are described and contrasted. The duration of survival was significantly longer from symptom onset to death in AD (mean 7.4 years) than in MID (mean 5.8 years). Most of this difference was accounted for by a longer duration between symptom onset and presentation to hospital care in AD (mean 3.2 years) than in MID (mean 2.4 years). Age at onset and gender did not influence survival duration in AD or MID. PMID- 1407248 TI - Studies on the incidence of dementia: the European perspective. AB - Dementing diseases, the most common of which are Alzheimer's disease and vascular dementia, are highly prevalent in Europe. To progress further in the search for the etiology of these diseases, incidence studies are needed. Comparison of the data of such studies will be important; the question of whether they produce comparable and interpretable data is therefore critical. We discuss the methodologic differences between earlier and more recent studies conducted in Europe that may account for some of the variation in the incidence rates of the dementia they report. Issues to be explored in the current European studies on the incidence of dementing diseases are also described. PMID- 1407249 TI - Epidemiology of myasthenia gravis in the province of Trento (northern Italy). AB - The epidemiology of myasthenia gravis (MG) was studied in the province of Trento (northern Italy) among 444,879 inhabitants. On prevalence day (December 31, 1990) the crude rate was 82.9 per million population: 113 for females and 50.7 for males. The incidence rate was 7.4 per million per year: 10.8 for females and 4.6 for males. Over the same observation period (1981-1990), we calculated a death rate of 1.12 per million population per year. MG predominates in females. Nevertheless, we observed some differences related to age and to presence of thymoma, and our data supports the recognition of three types of MG: (1) predominating in females with a peak frequency at about 20-29 years; (2) affecting both males and females, with a frequency increasing with age, and (3) associated with thymoma. PMID- 1407250 TI - Factors influencing long-term survival and disability among three-month stroke survivors. AB - 216 survivors of acute stroke were studied 3 months postictus to determine predictors of long-term survival and disability 20 months after the initial stroke. Factors predicting mortality were, in order of importance, old age, a history of ischaemic heart disease, low mental-test score, low serum cholesterol concentration, low Glasgow Coma Score on admission, and the presence of left ventricular hypertrophy. 73% of subjects were correctly classified by discriminant function analysis using these variables. Factors predicting poor functional outcome (Barthel Index 15) were a low Barthel Index at 3 months, old age, low mental-test score at 3 months and a low Glasgow Coma Score on admission. 70% of subjects were correctly classified into 3 functional-outcome groups using these variables. Stroke subtype and size, position, and the territory of the lesion on brain CT did not influence long-term outcome. We conclude that factors affecting long-term survival and disability are different from those affecting outcome immediately after stroke. PMID- 1407251 TI - A social and epidemiologic approach to use of technology in neurologic practice. AB - There is a consensus that technology is not always used appropriately in many medical care situations. In this article, a social and epidemiologic approach looks beyond biomedical issues to examine short- and long-term social consequences of using newer technology, particularly as related to neurologic disease. The prevailing belief that noninvasive neurodiagnostic testing is harmless for the patient often overlooks important physical and behavioral effects. High-technology subspecialization within neurology affects the matrix of patient care as well as the character of the specialty. The principles of clinical epidemiology and social medicine can help practitioners use neurotechnology more rationally. PMID- 1407252 TI - Practice patterns in neurology in India. AB - Sixteen Indian neurologists saw 1,850 patients over a sample 6-day working week. The average daily workload comprised 19 patients including 11 new cases. Epilepsy (27.0%), headache (19.0%) and cerebrovascular disorders (7.8%) were the commonest problems. Only 2.5% fell in the ICD-9-CM categories 780-799 consisting of symptoms, signs and ill-defined conditions. In 43% it was felt that the neurologic consult was not necessary. In the Indian setting this would suggest that emphasis should be on neurologic education of primary care physicians and internists for the appropriate utilization of limited resources. PMID- 1407253 TI - Vitamin A and Alzheimer's disease. PMID- 1407254 TI - [Psychological impact of periodic hemodialysis in the adult]. AB - End stage renal failure and its therapeutic procedures disorganize patient's world through the important modifications concerning his body and his personal, familial and socio-professional life. In proportion as the different stages of his psychological adjustment appear, the patient must mobilize several adaptive mechanisms to face fears, deterioration of body-image and numerous restrictions due to illness and its treatment. The quality of his personal response and of the family, society and medical staff responses will determine his compliance to the uremic status with its therapeutic pressures, and so the results of the treatment and the quality of his rehabilitation. PMID- 1407255 TI - [Thrombosis and disorders of hemostasis in nephrotic syndrome]. AB - Thromboses and disorders of hemostasis in nephrotic syndrome. Thromboembolic complications are common in nephrotic syndrome (NS). This article reviews the factors of thrombogenesis in NS, including: 1) a hypercoagulable state with platelet hyperaggregability, hyperfibrinogenemia and elevated factor VIII, decrease in plasma levels of coagulation inhibitors antithrombin III and free protein S, reduced fibrinolytic activity; 2) excessive intravascular thrombin formation marked by increased plasma levels of fibrinopeptide A. The intensity of hemostasis disorders coincides with that of NS. Most disorders are related to hypoalbuminemia and proteinuria. In agreement with experimental data, the role of intraglomerular activation of coagulation during active phases of glomerulopathies has to be considered. This could explain the predominance of renal vein thrombosis in several glomerulopathies with NS. Several coagulation disorders in SN have implications for therapy. PMID- 1407256 TI - [Acute renal insufficiency associated with lymphoma. A new case]. AB - We report on a case of acute renal failure secondary to relapse of a centrocytocentroblastic non-Hodgkin's lymphoma. Twenty-seven cases of acute renal failure due to lymphomatous infiltration of the kidneys have been so far reported. The clinical presentation is non-specific; the size of the kidneys appears normal or enlarged; diagnosis is confirmed by renal biopsy and/or CT scan examination. Chemotherapy and/or radiotherapy sometimes lead to dramatic improvement of renal function. However, prognosis is poor, mostly due to lymphomatous evolution. PMID- 1407258 TI - Peritonitis prevention in continuous ambulatory peritoneal dialysis. AB - Although peritonitis remains the major cause of morbidity in CAPD, peritonitis rates are declining in European and other countries. This article reviews approaches that are both decisive and promising concerning the prevention of peritonitis in CAPD. Clinical results with both reusable and single-use Y sets are discussed. These systems appear to have a significant impact on the reduction of intraluminal contamination, particularly Staphylococcus epidermidis. The importance of the flush-before-fill technique is reviewed in the context of the new disposable Y sets. In vitro studies confirm that 100 mls of fresh dialysate flushed from the new bag to the drainage bag at the appropriate time during the exchange can eliminate microorganisms that do not possess adherence factors, providing long periods of incubation are not encountered. Future prevention measures for the reduction of Staphylococcus aureus peritonitis are discussed in light of evidence identifying pre-CAPD nasal carriers as high risk patients for subsequent exit-site infection and S. aureus peritonitis. These measures include methods such as the application of antibiotics such as mupirocin to the anterior nares before and during CAPD. The roles of intraperitoneal IgG therapY and staphylococcal vaccination as additional therapeutic approaches to infection control in peritoneal dialysis are also discussed. PMID- 1407257 TI - [Crescentic Glomerulonephritis associated with gastric adenocarcinoma]. AB - The association of membranous glomerulonephritis with carcinoma and minimal change disease with Hogkin's disease are well established. In contrast cancer and crescentic glomerulonephritis is an uncommon association. We report a patient with gastric carcinoma who developed synchronously acute renal failure due to crescentic glomerulonephritis. Corticosteroid therapy, plasma exchanges and tumor resection was associated with a regression of renal failure. Carcinoma must be considered as a possible cause of crescentic glomerulonephritis. PMID- 1407259 TI - [Production of TNF-alpha during graft rejection and hemostasis disorders]. PMID- 1407260 TI - [Protein restriction rapidly diminishes the synthesis of transforming growth factor beta1 (TGFbeta1) during experimental glomerulonephritis]. PMID- 1407261 TI - The effect of age on protein composition of rat cerebral microvessels. AB - The effect of age on protein composition of cerebral microvessels was investigated by examining the content of glycosylation endproducts in cerebral microvessels isolated from young (3-6 month old), intermediate age (18 month) and aged (24-26 month old) Fischer 344 male rats and by quantitating various protein spots identified with two dimensional (2D) electrophoresis. The results indicate that aging in rats is not associated with significant increase in glycosylation of microvessel proteins. Of the 26 proteins in cerebral microvessels identified on the 2-D gel, ten showed significant age-related changes (p less than 0.0004) and in two of these the changes were significant as early as 18-months of age. A large acidic protein with a molecular weight of 144,000 and isoelectric point (pI) of 5.4 (Spot #1) was found only in aged rats. The results indicate that aging is associated with significant quantitative changes in protein composition of cerebral microvessels. It is possible that Spot #1 may be a novel biochemical marker of aging blood-brain barrier. PMID- 1407262 TI - Acetyl-L-carnitine influences the fluidity of brain microsomes and of liposomes made of rat brain microsomal lipid extracts. AB - The fluorescence anisotropy (r) of diphenylhexatriene (DPH) was measured in different preparations (bovine spinal cord phosphatidylserine liposomes, rat brain microsomes, liposomes made with rat brain microsomal lipid having different phospholipid:cholesterol ratios) at temperatures ranging from 10 degrees to 55 degrees C. Phosphatidylserine liposomes exhibited an exponential relationship of r versus temperature, whereas the relationship shown by microsomes and liposomes prepared with microsomal lipid extracts was a linear one. The removal of protein and high phospholipid:cholesterol ratios decreased the slope of the lines (fluidity increased), although the intercept was unaffected. This means that differences were better appreciated at high temperatures and were well evident at 37 degrees C. Acetyl-L-carnitine decreased r in rat brain microsomes and in liposomes made with microsomal lipids with different phospholipid:cholesterol ratios. The fluidifying effect of acetyl-L-carnitine was mild but statistically significant and could explain, at least in part, the data reported in the literature of acetyl-L-carnitine acting on some parameters affected by ageing. Besides, acetyl-L-carnitine seemed to oppose the changes of viscosity due to lipid peroxidation, which has been reported to increase in ageing and dementia. L carnitine shares the properties of its acetyl ester, but only in part. PMID- 1407263 TI - Free radical scavenging systems of rat astroglial cells in primary culture: effects of anoxia and drug treatment. AB - Hypoxic injury of rat astroglial cells in primary culture initiates several modifications of their functional integrity. A significant decrease of the cellular oxygen consumption was observed in astrocytes submitted to a 15 h low oxygen pressure. The addition of almitrine (dialylamino-4',6'-triazinyl 2')-1 (bis-parafluorobenzydryl)-4-piperazine, a chemoreceptor agonist, restored almost completely the respiratory activity of the hypoxia treated cells. In order to test the hypothesis that oxygen free radical formation may contribute to the cellular damage resulting from ischemia, the activities of the following antioxidant enzymatic systems have been determined in the cultured astrocytes: Cu,Zn- and Mn-superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione reductase (GSH-RED), and catalase (CAT). Only a significant and specific decrease of the Mn-SOD activity was observed after the hypoxia-normoxia exposure. The other oxygen radical scavenging systems were not modified. The addition of almitrine antagonized the decrease of the Mn-SOD activity observed in the low oxygen pressure treated cells, but results clearly point-out the importance of oxygen radical production in the astroglial response after hypoxic injury. A beneficial effect of almitrine toward the observed alteration has been underlined. It is suggested that some mitochondrial alterations could be related to some aspects of the astroglial hypoxic stress. PMID- 1407264 TI - Effects of chronic bifemelane hydrochloride administration on receptors for N methyl-D-aspartate in the aged-rat brain. AB - We assayed N-methyl-D-aspartate (NMDA) receptors [3H]3-(2-carboxypiperazin-4 yl)propyl-1-phosphonic acid ([3H]CPP) bindings) and evaluated their distribution in the brain by quantitative autoradiography in young adult and aged rats. In the young adult rats, NMDA receptors were present at relatively high concentrations in the cerebral cortex and hippocampus. In the aged rats, NMDA receptors were decreased in the nealy all areas of the brain, especially in the cerebral cortex and hippocampus. Chronic administration of bifemelane hydrochloride, a drug for sequela of cerebrovascular diseased, at a dose of 15 mg/kg/day for 14 days, markedly attenuated these decrease in NMDA receptors. Since NMDA receptors are considered to be involved in memory and learning processes, our results suggest that bifemelane hydrochloride may be applicable to the treatment of disturbed memory and learning. PMID- 1407265 TI - Regional distribution of tyrosine, tryptophan, and their metabolites in the brain of epileptic El mice. AB - Tyrosine, tryptophan, and their metabolites in the brain of ddY, non-stimulated El (El (-)), and stimulated El (El (+)) mice were measured using the three dimensional HPLC. The tryptophan content was lower in El (+) than ddY and El (-) mice. The 5-hydroxytryptophan content was much higher in both El groups. The serotonin content of El (+) was higher than that of ddY and El (-) mice. The kynurenine content was remarkably high in the El mice. The dopamine content was lower in El (-) than in ddY mice, whereas it was greater in El (+) than in El (-) mice. The norepinephrine showed higher levels in El (+) mice. These facts suggest that El mice possess congenital metabolic abnormalities of tryptophan and tyrosine and that kynurenine may play an important role as convulsant in El mice seizures along with changes in serotonin, dopamine, and norepinephrine that are inhibitory agents and responded to the repetitive convulsions. PMID- 1407266 TI - Secretion of immunoreactive endothelin-1 by capillary and microvascular endothelium of human brain. AB - Modulation of immunoreactive endothelin-1 (IR-ET-1) production by vasoactive substances was investigated in cultured endothelial cells (EC) derived from capillaries and microvessels of human brain. Peptides, catecholamines, thrombin, protein kinase C-activating phorbol ester, and calcium ionophore enhanced the secretion of IR-ET-1. The known vasoconstrictive peptides, angiotensin II (Ang II) and arginine-vasopressin (AVP) dose-dependently stimulated the endothelial secretion of IR-ET-1. The angiotensin and vasopressin-inducible production of IR ET-1 was completely inhibited by their respective receptor antagonists [Sar1, Ala8]-angiotensin II and [1-6 (beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-O-methyl-tyrosine]. The results indicate that the peptide stimulated secretion of IR-ET-1 is receptor-mediated in EC which have specific angiotensin II and arginine-vasopressin receptors. These findings represent the first demonstration of IR-ET-1 production by capillary and microvascular endothelium of human brain. PMID- 1407267 TI - Comparative study between 4-aminobutyrate-2-oxoglutarate aminotransferase (GABA T) from rat forebrain and cerebellum. AB - In this study differences in the biochemical properties of 4-aminobutyric acid aminotransferase (GABA-T) from forebrain and cerebellum were detected. These differences may be related to: a) the characteristics of the catalytic site, b) the substrate affinities and c) their pyridoxal-phosphate requirements which suggests that PLP could be a physiological regulator of these forms of brain GABA T. PMID- 1407268 TI - Differential effects of ethanol on membrane-bound and soluble acetylcholinesterase from sarcoplasmic reticulum membranes. AB - The action of ethanol on the activity of membrane-bound and soluble acetylcholinesterase (AChE) in sarcoplasmic reticulum of skeletal muscle has been studied. Treatment of membranes with 2.5-12.5% v/v ethanol produced a slight stimulation of the AChE activity and inhibition at higher concentration. The enzyme remained associated with the membranes after these treatments. The enzyme solubilized with Triton X-100 was inhibited by ethanol in a time-independent manner. Isolated 16 S (A12), 10.5 S (G4) and 4.5 S (G1) forms of AChE were inhibited by ethanol to a similar extent. Samples were reversibly inhibited by ethanol, up to 12.5% v/v, and irreversibly at higher concentrations. Kinetic studies performed with isolated forms in the presence of 5-12.5% v/v ethanol showed that the solvent behaved as a competitive inhibitor of the asymmetric form but as a mixed inhibitor of the tetrameric and monomeric forms. The results show that the solvent interacts with active and/or regulatory sites of AChE from muscle microsomes. PMID- 1407269 TI - 2-Guanidinoethanol increased dopamine release and 3,4-dihydroxyphenylacetic acid content, but not homovanillic acid content in the rat brain: electroneurochemical and enzymological studies. AB - The effects of 2-guanidinoethanol (GEt) on the release of monoamines and on the activity of their degrading enzymes were studied in order to investigate why 3,4 dihydroxyphenylacetic acid (DO-PAC) increased to a much greater extent than homovanillic acid (HVA) after GEt injection into rat brain. In differential pulse voltammograms recorded using an electrochemically treated carbon fiber electrode, two distinct oxidation peaks, one at 130mV (DOPAC peak) and the other at 300 mV (5-hydroxyindoleacetic acid (5-HIAA) peak), were observed. In the hippocampus, the DOPAC peak increased markedly compared to the peak height recorded prior to the intracerebroventricular injection of GEt (6 mumol). Although the DOPAC peak height increased to 350% 4 hours after GEt injection, the 5-HIAA peak showed no change. In the striatum, the DOPAC peak increased to 150% 3 hours after GEt injection. Serial changes in the extracellular levels of DOPAC, HVA, and 5-HIAA were monitored in the striatum after GEt injection, using an in vivo brain micro dialysis technique. Although the DOPAC levels strated to increase 80 minutes after GEt injection, HVA and 5-HIAA levels showed no change. On the other hand, monoamineoxidase, which metabolizes dopamine to DOPAC, was not activated and catechol-O-methyltransferase, which metabolizes DOPAC to HVA, were not inhibited by 5 mM of GEt in vitro. These data suggested that GEt increased the release of dopamine, but not of serotonin, and that GEt might restrict the DOPAC transport system. PMID- 1407270 TI - Special issue dedicated to Dr. Alan N. Davison. PMID- 1407271 TI - Effect of 2,5-hexanedione and 3,4-dimethyl-2,5-hexanedione on retrograde axonal transport in sciatic nerve. AB - The effects of systemically introduced neurotoxic solvents 2,5-hexanedione (2,5 HD) and 3,4-dimethyl-2,5-hexanedione (DMHD) on retrograde axonal transport (RT) of 125I-labeled tetanus toxin (TT) was studied in rat and mouse sciatic nerves. The rate of retrograde transport of TT in control rat sciatic nerves was slightly higher (6.8 +/- 0.4 mm/h) than in mouse sciatic nerves (5.4 +/- 0.5 mm/h). A single high dose of 2,5-HD (1,000 mg/kg, i.p.) produced a time-dependent effect on RT in mouse sciatic nerves. 2,5-HD caused a gradual decrease in the velocity of RT (approximately 65% inhibition between 2.0-2.5 h) with a reversal to normal rate 3-5 h after the toxin administration. The effect of DMHD on RT was examined following semi-chronic treatment in rats. DMHD caused a significant decrease (approximately 50%) in the rate of TT transport, in addition, it produced weight loss and hind-limb paralysis. PMID- 1407272 TI - Neurochemical changes in rats chronically treated with a high concentration of manganese chloride. AB - Several neurochemical parameters were studied in brain regions of rats chronically treated with a high concentration of manganese chloride (20 mg MnCl2.4H2O per ml. of drinking water) throughout development until adulthood. Large increases in Mn accumulation were found in all brain regions (hypothalamus, +530%; striatum, +479%; other regions, +152 to +250%) of Mn-treated adult rats. In these animals, Ca levels were decreased (-20 to -46%) in cerebellum, hypothalamus, and cerebral cortex but were increased (+186%) in midbrain. Mg levels were decreased (-12 to -32%) in pons and medulla, midbrain, and cerebellum. Fe levels were increased (+95%) in striatum but were decreased (-28%) in cerebral cortex. Cu levels were increased (+43 to +100%) in pons and medulla and striatum but Zn levels were decreased (-30%) in pons and medulla. Na levels were increased (+22%) in striatum but those of K and Cl remained unchanged. Type A monoamine oxidase activities were decreased (-13 to -16%) in midbrain, striatum, and cerebral cortex, but type B monoamine oxidase activities decreased (-13%) only in hypothalamus. Acetylcholinesterase activities were increased (+20 to +22%) in striatum and cerebellum. The results are consistent with our hypothesis that chronic manganese encephalopathy not only affects brain metabolism of Mn but also that of other metals. PMID- 1407273 TI - Taurine biosynthesis enzyme cysteine sulfinate decarboxylase (CSD) from brain: the long and tricky trail to identification. PMID- 1407274 TI - Structure and regulation of the MinK potassium channel. AB - MinK is a novel protein which induces an extremely slowly activating potassium channel when expressed in Xenopus oocytes. We discuss the properties and regulation of the current and localization and possible physiological roles of the MinK protein. PMID- 1407276 TI - The properties of cultured fetal human and rat brain tissue and its use as grafts for the relief of the parkinsonian syndrome. AB - Primary cultures were derived from human fetal ventral mesencephalon and cerebral cortex at 7-11 weeks gestation, and from fetal rat mesencephalon and cortex at embryonic day 14-15. Immunohistochemical analysis of the mesencephalic cultures using antibodies to tyrosine hydroxylase (TH) showed between 0.1-0.5% of human cells to be TH positive and 0.1-1% of rat cells to be TH positive. HPLC analysis of extracts from the cultures showed that they had the ability to synthesise and store dopamine. Implantation of the cultured human and rat mesencephalic tissue into a 6-hydroxydopamine rat model of Parkinson's disease produced marked recovery from amphetamine induced rotational asymmetry in the recipient rats, but no such recovery was observed following implantation of cortical cultures. Histological examination demonstrated the presence of surviving human mesencephalic and cortical grafts at least 6 months after implantation. Implants of cultured fetal rat tissue were less obviously but still significantly effective in these experiments. These rat tissue grafts were detectable for periods of at least 6-8 weeks by histological staining. PMID- 1407275 TI - Quantitative aspects of reactive gliosis: a review. AB - Recent studies of gliosis in a variety of animal models are reviewed. The models include brain injury, neurotoxic damage, genetic diseases and inflammatory demyelination. These studies show that reactive gliosis is not a stereotypic response, but varies widely in duration, degree of hyperplasia, and time course of expression of GFAP immunostaining, content and mRNA. We conclude that there are different biological mechanisms for induction and maintenance of reactive gliosis, which, depending on the kind of tissue damage, result in different expressions of the gliotic response. PMID- 1407277 TI - Fluids of the brain and the pathogenesis of MS. AB - The plaques of multiple sclerosis are generally thought to spread outwards from central veins. We propose that periventricular plaques in the cerebral hemispheres, and superficial plaques in the brain stem and spinal cord, point to the importance of demyelinating factors in the cerebrospinal fluid. PMID- 1407278 TI - Novel brain-specific bovine cDNA for a developmentally regulated mRNA encoding a putative new member of the leucine-rich glycoprotein (LRG) family. AB - We have isolated a bovine cDNA which hybridized to a 2 kb mRNA specifically expressed in the rat and human brain. The mRNA was abundantly expressed in adult but not 21-week old human brain. In the rat brain, there was very little of the transcript in 15-day old fetus but it increased in abundance with development, being most abundant in the adult and expressed in all brain regions. Genomic analysis showed that the sequence is single copy and conserved in all vertebrates examined, including chicken. The 702 bp partial cDNA encoded an amino acid sequence for a putative member of the leucine-rich glycoprotein (LRG) family known to be involved in cell adhesion/recognition. The predicted polypeptide displayed sequence identity with that recently reported for the human oligodendrocyte-myelin glycoprotein. This cDNA should prove useful in further investigations on brain-specific cell-cell interactions. PMID- 1407280 TI - Monoclonal antibody 14E recognizes an antigen common to human oligodendrocytes, Schwann cells, Bergmann glia, and a subpopulation of reactive glia. AB - The monoclonal antibody 14E immunocytochemically stains the nuclear membrane of oligodendrocytes but not myelin in tissue sections of adult normal human white matter. The nuclear membranes of Schwann cells in human peripheral nerve and cerebellar Bergmann glia were also visualized with this antibody. In actively demyelinating multiple sclerosis plaques the 14E antibody stained increased numbers of oligodendrocytes and the nuclei, perikarya and cell processes of hypertrophic glia, which were often multinucleate. Scattered small groups of these hypertrophic glia were present in areas of dense astrogliosis in acute plaques. The 14E-positive hypertrophic cells could be either a subpopulation of reactive astrocytes or bipotential glial precursors. PMID- 1407279 TI - Energy metabolism and selective neuronal vulnerability following global cerebral ischemia. AB - A short period of global ischemia results in the death of selected subpopulations of neurons. Some advances have been made in understanding events which might contribute to the selectivity of this damage but the cellular changes which culminate in neuronal death remain poorly defined. This overview examines the metabolic state of tissue in the post-ischemic period and the relationship of changes to the development of damage in areas containing ischemia-susceptible neurons. During early recirculation there is substantial recovery of ATP, phosphocreatine and related metabolites in all brain regions. However, this recovery does not signal restitution of normal energy metabolism as reductions of the oxidative metabolism of glucose are seen in many areas and may persist for several days. Furthermore, decreases in pyruvate-supported respiration develop in mitochondria from at least one ischemia-susceptible region at times coincident with the earliest histological evidence of ischemia-induced degeneration. These mitochondrial changes could simply be an early marker of irreversible damage but the available evidence is equally consistent with these contributing to the degenerative process and offering a potential site for therapeutic intervention. PMID- 1407281 TI - [Indications for the shunt treatment of children with cerebellar astrocytoma]. AB - In the years 1980-1987 the number of children aged from 11 months to 15 years treated for cerebellar astrocytoma was 113, the mean age was 5.4 years. Shunt insertion preceding the main surgical treatment was done in 10 cases (9%). After the operation shunt was necessary in 15 cases, that is 15% of cases not undergoing shunt insertion before the operation. In all, shunting was necessary in 22% of patients with cerebellar astrocytoma. In the conclusions the authors suggest indications to shunting in various age groups in cases of cerebellar astrocytoma. PMID- 1407282 TI - [Brain tumors in the records of the Department of Neurosurgery in Rzeszow 1976 1989]. AB - The authors present the results of surgical treatment of 232 patients with brain tumours operated on in the neurosurgery centre in Rzeszow. In 84% of cases it was possible to remove the tumor radically, 44% of the patients were subjected to postoperative radiotherapy. The relationship is discussed between the operative results and the location of tumor, its microscopic structure and patient's age. PMID- 1407283 TI - [Colloid cysts of the III ventricle. Report on our 8 cases operated on by the interhemispheric approach]. AB - Between 1984 and 1990, 12 patients with colloid cysts of the third ventricle were operated on. 8 of them underwent surgery by an anterior transcallosal approach with very good result. The authors discuss the different methods of surgical treatment using the microsurgical technique and present the advantages of the midline approach. PMID- 1407284 TI - [Diagnosis and treatment of recurrent brain glioma]. AB - In the period from Jan 1 1984 to Dec 31 1990 clinical and radiological evidence of brain glioma was found in 120 cases treated previously surgically. The group comprised 55 women (46%) and 65 men (54%). At the time of tumour diagnosis their age was ranged 40 to 60 years. All patients received non-radical surgical treatment, supplemented with Co60 radiation in 104 cases, in 3 cases Co60 treatment was given together with chemotherapy (CCNU) and 12 patients received no complementary treatment. Thirty four patients (28%) had reoperations, in two cases even twice. In 86 cases (72%) treatment was palliative. Three types of secondary tumour regrowth were discerned. Reoperation prolonged survival and its effectiveness was greatest in regrowth type I. The shortest survival till the appearance of regrowth signs and the shortest survival after recurrence were in type II of regrowth. PMID- 1407285 TI - [Factors affecting the quality of life of patients treated by a combined method for poorly differentiated supratentorial glioma]. AB - The quality of life of patients treated for brain tumours and the length of survival are important factors making possible the evaluation of treatment effectiveness. Changes of life quality evaluated by the Karnofsky scale were analysed in a group of 56 patients who have received combined treatment for poorly differentiated supratentorial gliomas. Life quality changes were evaluated after completion of surgical and radiological treatment in relation to preoperative status. The influence of various clinical factors on life quality changes was evaluated. Surgical treatment and tumour site had a significant effect on the stabilization or slight improvement of life quality. The direction and extent of life quality changes were related to surgery, with further change after radiotherapy. PMID- 1407287 TI - [Brachytherapy of brain gliomas]. AB - Radiotherapy is considered presently the most advantageous supplementary method after surgical treatment for gliomas. The limitations of classical teletherapy cause that interstitial radiation may become preferable. The authors present the theoretical principles and practical application of brachytherapy in 10 cases of glioma. Closed radioactive sources were used in form of I125 implanted stereotactically into brain tumours for a period sufficient for providing therapeutic radiation dose to the border of the tumour. The doses received by tumour borders ranged from 812 to 4560 cGy, and the mean dose was 2064 cGy. Five patients were given additionally 6000 cGy by teleradiotherapy. PMID- 1407286 TI - [Transplantation of fetal dopaminergic cells in Parkinson disease]. AB - Four patients with severe form of Parkinson's disease received transplantation of fetal dopaminergic cells into the caput of the caudate nucleus. The operation was done by an original method using a device designed specially for this purpose. In all cases the duration of the disease was 10 to 15 years, and the predominating signs were tremor, bradykinesia, and markedly pronounced side effects of the treatment (on-off syndrome and involuntary movements). One patients died 5 weeks after the operation. Autopsy demonstrated good survival of the transplanted cells with good integration with the brain of the recipient and traces of positive immunocytochemical reaction for tyrosine hydroxylase. In the other patients a significant clinical improvement was noted after the operation, with reduced intensity of parkinsonian symptomatology, shortening of the duration of the off phase, improved motor ability and reduced intensity of the involuntary movements. The longest follow-up was 24 months. PMID- 1407288 TI - [Use of a stereotaxic method in the diagnosis and treatment of brain neoplasms in children]. AB - The paper presents the possibility of application of the stereotactic method in the diagnosis and treatment of pediatric brain tumours, based on the material of the Dept. of Stereotactic Neurosurgery of the University Clinic in Homburg-Saar (Germany). The basic theoretical principles and diagnostic potential of serial biopsy and intraoperative diagnosis are presented. Shown are new therapeutic possibilities created by interstitial brachytherapy. The results obtained in stereotactic treatment of brain tumours are deemed satisfactory, as the method enables a cause-oriented treatment in cases hitherto inoperable because of localisation and resistant to megavolt radiotherapy because of radiobiological characteristics of the given neoplasm. PMID- 1407289 TI - [Clinical analysis of 27 cases of primary lymphoma of the central nervous system]. AB - Clinical analysis of 27 patients with primary central nervous system lymphoma- Out of 4397 patients with intracranial neoplasms treated in the Department of Neurosurgery Medical Academy in Poznan between years 1956-1990, 27 patients i.e. 0.6% had primary central nervous system lymphoma. The patients age ranged from 15 to 63 years. In most patients the tumour was located in the temporo-parietal region. All patients were treated surgically, and then some received radio and/or chemotherapy. In spite of combined therapy the results of treatment are unsatisfactory, the median survival time is between 2 and 4 months. PMID- 1407290 TI - [Early results of surgical treatment of discopathy at the Neurosurgical Clinic, Medical Academy, in Bialystok]. AB - The author discusses 876 cases of discopathy treated surgically at the Neurosurgery Department in 1987. Better results were obtained in patients operated on within 6 months after the development of the first symptoms of disc prolapse. PMID- 1407291 TI - [Reoperations in lumbar discopathies]. AB - In the years 1976-1990 at the Neurosurgery Centre in Rzeszow 938 patients were treated surgically for lumbar discopathy. Reoperation was necessary in 5.4% of cases. In 0.6% of them purulent wound infection was the cause, in the remaining 4.8% lacking improvement or recurrence of sciatic pain after 1 month to 12 years. In 2.2% of cases the cause of pain recurrence was recurrent hernia at the same or other level, and after its removal sciatic pain disappeared. Root compression by cicatricial tissue or osteophyte caused reoperation in 1% and surgical decompression of the root gave only minor improvement. Lacking improvement after the first operation was due in 0.7% of cases to a fragment of the nucleus pulposus left in the vertebral canal and in 0.6% the cause was failure to recognize two-level discopathy. After reoperation in such cases all pains regressed. The analysis showed that the frequency of repeated interventions would be diminished by careful excochleation of the intervertebral space, operative revision of the space with comparison with the results of radiculography and clinical examination, and not too late decision of operation. PMID- 1407292 TI - [Late results of surgical treatment of multilevel intervertebral disk displacement in the lumbar spine]. PMID- 1407293 TI - [Usefulness of computerized myelotomography in the diagnosis of discopathy of the cervical spine]. AB - The authors compared the results of preoperative computer-assisted myelography (CAM) with surgical findings in 45 patients with suspected cervical disc disease. In 98% CAM gave full and proper diagnosis confirmed by surgery. Only in one patient, the preoperative diagnosis was extraspinal tumour, and surgery revealed prolapsed nucleus pulposus lying freely on the anterior wall of the dural sac. In authors's opinion, CAM is sufficient for planning of surgical treatment in cervical disc disease, and other radiological studies, myelography or nuclear magnetic resonance tomography are usually not necessary. PMID- 1407294 TI - [Evaluation of work capacity in cases of discopathy of the lumbosacral segment of the spine]. AB - The ability to resume occupational work in cases of lumbar discopathy was assessed in an analysis of 1104 cases treated in a period of 25 years. The assessment was analysed in relation to the following factors: 1. disease duration, 2. discopathy type, 3. patient's age, 4. occupation type, 5. treatment. The paper contains a number of observations concerning the management of lumbar discopathy, and suggestions related to working ability expertise in such cases. PMID- 1407296 TI - [Brain mapping in atonic epileptic attacks with consciousness disorders at school age]. AB - The paper presents the results of the analysis of atonic epileptic seizures with application of brain mapping eeg. The views to date on the pathogenesis of atonic seizures could be based on the assumptions of centrencephalic epilepsy voiced by Penfield and Jasper. The present investigations and electrophysiological-clinical observations support, however, contrary to the concept of Penfield and Jasper, the cortical origin of these seizures. The discussion on the clinical forms of atonic seizures in epilepsy, confirmed by analysis of brain mapping in the domain of frequencies and amplitude distribution, in the form of brain topograms, allows for the concept of cortical origin of these seizures with the probability of localisation of the epileptic focus, as in here presented case, in the anterior right paramedial frontal region of the brain. PMID- 1407295 TI - [Prognostic value of evoked potentials of the spinal cord in surgical treatment of lumbar intervertebral disk prolapse]. AB - Spinal potentials were evoked stimulating the peripheral nerves of lower extremities in healthy people and in patients with manifestations of lumbar disc prolapse. The patients were studied before and early after the operation. In healthy subjects the velocity of impulse conduction was nearly identical when both extremities were compared. In the patients the test before the operation revealed a significant prolongation of the latency of the potentials on the side of the damaged nerve root. After the operation a significant difference between the healthy and the affected side was still present early after the operation but it was significantly smaller than before the operation since the conduction velocity was improved on the side of the operation. The study of spinal evoked potentials makes possible recognition of disturbed function of nerve roots, and after the operation the rate of changes of potential latency is an important prognostic sign. PMID- 1407297 TI - [Brain mapping in Parkinson disease treated by cryothalamotomy]. AB - Brain mapping of the cerebral bioelectric activity was done by the BEAM method in 20 patients with Parkinson's disease treated by cryothalamotomy. Conventional egg examinations demonstrating relatively small changes of the type of local asymmetry of frequencies and/or amplitudes, sporadic focal changes, and sporadic generalized and disseminated generalized changes were analysed in a computer system in the domain of frequency and time. Brain mapping demonstrated very distinctly the asymmetry in the frequency bands alpha and beta. On the operated side a regular alpha rhythm of lower frequency but higher amplitude dominated in the brain hemisphere. On the intact side a quick beta rhythm prevailed and an irregular alpha rhythm was noticeable. This phenomenon described by analysis in the domain of frequency confirms the unilateral synchronizing influence of thalamotomy on the bioelectric activity of the operated brain hemisphere and may correlate with the functional motor improvement noted in the operated subjects. In three cases with a longer course of the disease analysis in the frequency domain demonstrated the presence of generalized diffused slow waves in both frontal regions. These changes correlated with mental insufficiency of the examined patients. PMID- 1407299 TI - [Results of the treatment of idiopathic hydrocephalus by shunt implantation after computerized cisternography]. AB - A retrospective study was reported of 19 patients (10 males and 9 females aged from 11 to 65 years) with idiopathic hydrocephalus treated by shunt implantation after qualification for this treatment based on computed tomocisternography. Clinical improvement was noted in 16 patients (84%), and after 2 months the therapeutic results by Black's scale were good in 13 patients (65%). PMID- 1407298 TI - [Results of surgical treatment of 35 giant aneurysms]. AB - Results of surgical treatment of 35 giant aneurysms. Over the last 4 years (1988 1991) 35 large aneurysms were operated on in the Department of Neurosurgery Medical Academy in Gdansk. This material is divided in two groups: to group I belong these aneurysms of diameter 2 to 2.5 cm and to group II those above the diameter of 2.5 cm. Surgery in group I was always performed by means of direct attack, while in group II sometimes STA-MTA by-pass, combined with carotid ligation was applied. The by-pass procedure is particularly advocated in the aneurysms of the infraclinoid portion of ICA and those originating from the junction of the ophthalmic and ICA (carotid-ophthalmic). With the progress of operative technique and routine application of temporary clipping of the vessels adjacent to and supplying the aneurysm, the number of by-pass operations has been limited to those of the infraclinoid portion of ICA only. Only in 1 case the result was unfavourable, in 2 cases it was fair and in 2 other cases it was excellent. PMID- 1407300 TI - [Changes in CSF resorption resistance. Experimental studies]. AB - Lumbar infusion tests (IT) with different infusion rates (0.06 ml/min-1.2 ml/min) were used in order to investigate the intracranial pressure (ICP) and CSF outflow resistance (R) changes. Two groups of animals were studied: control group and animals with an 0.8 ml epidural balloon. In control group (without balloon) significant differences in ICP and R values between the increasing and decreasing IT curve were found. The most pronounced changes were noticed right after the highest infusion rate (40% for ICP value and 49% for R value). The results in the balloon group were very similar and the only difference were delayed ICP and R changes. The results obtained suggest that the determined R values are specific for the applied infusion rate and this phenomenon has to be taken into account in all human studies. PMID- 1407301 TI - [Metabolic effects of experimental thermal damage of the brain in rats--cold lesion]. AB - Experimental thermal brain injury leads to significant reduction of glucose utilization in the damaged hemisphere particularly evident in the cortex 3 days after the injury. The rate of development of these changes is not parallel with the observed damage to the blood-brain barrier, coexistent brain oedema and slight disturbances of cerebral blood flow. In a series of experiments it was possible to demonstrate significant accumulation of glucose, high-energy phosphate compounds and their metabolites in the areas of the brain near the damaged part. The authors think that this is an evidence of reduced glucose uptake by the brain resulting from reduced energy needs of the damaged brain tissue despite sufficient supply of energy-yielding substances. Since cerebral metabolism and functions are in close interrelationship reduced glucose metabolism in the damaged tissue leads to reduced activity of the cortex, which contributes to transient (or permanent) functional neurological deficits observed after cranio-cerebral trauma in humans. The knowledge and understanding of these processes regulating the development of local depression of cerebral metabolic processes may help in better results of treatment in such cases. PMID- 1407303 TI - [Late results of the treatment of trigeminal neuralgia by the method of thermocoagulation of the gasserian ganglion]. AB - The authors reviewed a series of 38 consecutive patients with trigeminal neuralgia treated by percutaneous thermocoagulation in 1984-90. In 10 patients in whom the result of the treatment was unsatisfactory the coagulation was repeated (in 2 out of 10 twice). The analysis of the results showed that good outcome was connected with permanent anaesthesia in the area innervated by the coagulated branch. If anaesthesia was not present 24 hours after the treatment, it suggested that an insufficient lesion was done and consequently unsatisfactory result was likely. In patients in whom there was a sensory impairment after either thermocoagulation or other form of treatment (injection of alcohol or rhizotomy) repeated thermocoagulation not only did not give good results but could lead to worsening of the pain. PMID- 1407302 TI - [Our experience with microsurgical methods of the treatment of injuries of the radial nerve caused by humeral fracture]. AB - Experiences are presented with the surgical treatment of 33 patients with traumatic radial nerve injuries after humerus fracture. Diagnostic and surgical difficulties of primary orthopaedic humerus fragment union by osteosynthesis with simultaneous evaluation of the damaged nerve. In the group of patients who had been given primary orthopaedic treatment the causes were analysed of reinnervation failure. In another group of patients undergoing metal plate removal after full bone union had been achieved the own experiences are presented related to an improved method of operative approach and delayed reconstruction of the damaged nerve. The authors suggest reconstruction of radial nerve injury after humerus fracture by specialized teams of orthopaedic surgeons and neurosurgeons. PMID- 1407304 TI - [Use of the Nd:YAG laser in surgical treatment of intracranial tumors]. AB - The Nd:YAG laser was used between January 1989 and March 1991 in 63 cases of intracranial tumours, including 32 meningiomas, 16 gliomas (including 11 glioblastomas), 8 acoustic neurinomas, 11 metastatic brain tumours. In 76.2% of cases very good results were obtained. The Nd:YAG laser was found to be particular value in the treatment of vascular intracranial tumours, especially meningiomas and metastatic tumours. The ability of the Nd:YAG laser to shrink and devascularize these tumours, was useful in neurosurgical operations. The no-touch technique, minimal or no thermal effect on surrounding tissues, better haemostasis and precision allow for easier removal of acoustic nerve tumours. The Nd:YAG laser is very useful in the operations close to the very important for life areas of the brain. The major advantages of laser include reduction of mechanical trauma, reduction of blood loss, and more radical removal of intracranial tumours. PMID- 1407305 TI - [Evaluation of the usefulness of cerebral perfusion pressure in threatened cerebral ischemia]. AB - The Cushing response was produced using the lumbar infusions in cats. The following parameters were recorded and computed: arterial blood pressure (ABP), central venous pressure (CVP), intracranial pressure (ICP), heart rate and ECG. The lactate concentration was studied in brain stem and brain cortex. The analysis of ABP and ICP recordings showed in some cases that the Cushing response was obtained at CPP over 60 mmHg. The role of adrenergic reaction in Cushing phenomenon was confirmed by the increase in blood catecholamine concentration and typical adrenergic changes in ECG pattern. PMID- 1407306 TI - [Analysis of selected prognostic factors in patients with ruptured cerebral aneurysms operated-on in the early period]. AB - An analysis of certain clinical and laboratory findings of 80 patients with ruptured intracranial aneurysms was done. All of them underwent an operation in acute stage. The following prognostic factors were analysed: age of patient, sex, number of previous subarachnoid hemorrhages (SAH), clinical status according to the Hunt-Hess scale, CT finding according to Fisher scale, location and number of aneurysms, time of operation, Nimodipine treatment, body temperature, serum sodium level, white blood count just before operation, mean blood pressure, coexistence of heart and kidney disease. A special computer programme was used to analyse the value of the above factors on follow-up and the final results of the ruptured intracranial aneurysms treated surgically in acute stage. PMID- 1407307 TI - [Late results of surgical treatment of chronic subdural hematoma at the Department of Neurosurgery of the Merged District Hospital in Rzeszow 1976-1987]. AB - Late results of the surgical treatment of chronic subdural haematomas in 117 patients after 1-13 years of follow-up are reported. Sporadic headaches were the complaint in 24% of cases, sporadic dizziness in 17.5%, and weak recent memory in 7.2%. Neurological deficit was found in 6.6% of cases. The complaints and neurological deficit present late after the operation caused no limitation of self-dependence and no help of others was necessary. EEG changes were present in 13.7% of cases late after the operation and had a decreasing tendency. The number of patients quitting work and receiving disability pension was greater than the number of those voicing complaints or showing neurological deficit. The wide range of works done by these "disabled" shows that the criteria of recognizing working disability are very imperfect. In 90 patients in whom the brain failed to expand spontaneously after haematoma evacuation 0.9% NaCl was given intrathecally and brain expansion was achieved. In this group complaints and deficits were much less frequent than in those in whom brain expansion was not aided. In the group with slower development of haematoma complaints and deficits were less frequent than in those with haematoma developing before one month after trauma. PMID- 1407308 TI - [Traumatic and spontaneous cerebral hematoma]. AB - The authors analyzed 231 patients--14% of all intracranial haematomas treated in the Department of Neurosurgery in Poznan between 1962 and 1990. The patients were divided into 3 following subgroups: I--cases of spontaneous haematomas (identified and unidentified)--30%, II--haematomas of unknown aetiology, but after mild head trauma--27%, III--traumatic haematomas--43%. Increased risk of mortality was observed in cases with intracerebral posttraumatic haematomas. These patients demonstrated diffuse cerebral oedema and multifocal contusions. In the subgroup of patients with spontaneous cerebral haematomas vascular malformation was present during operation or/and in histopathological study--65%. PMID- 1407309 TI - [Surgical treatment of cerebral hematoma using an endoscopic method]. AB - In the period from January 1990 to March 1991 in the Neurosurgery Department, Mining Industry Health Service Hospital in Sosnowiec 21 operations of evacuation of supratentorial intracranial haematomas were carried out by the endoscopic method using a neuroendoscope produced by K. Storz. The indication to this operation was a serious condition of the patients up to 10 points of the Glasgow scale, strictly limited extent of haematoma and ventricular system shifting over 5 mm in computed tomography. The mass of the haematoma could be evacuated in 70 90% and the patients were spared extensive craniotomy. Two patients had reoperations due to renewed haematoma formation. 48% of the patients left the hospital in good condition without neurological deficits and 42.5% had focal neurological signs. PMID- 1407310 TI - [Remarks on conservative treatment of cerebral hematoma]. AB - Authors present 38 patients treated non-operatively because of intracerebral haematomas since 1988 till 1990 in ++Neuro-traumatological Ward Medical Academy of Lodz. The aforementioned data revealed that patients could be treated non invasively if: 1. On admittance to the ward they were in good general condition they were conscious or their awareness was uptuned a bit. 2. Compression of ventricular system and even slight replacement of media line structures was not an indication to operative treatment if the consciousness of the patients had been good, had not deteriorated during the treatment and on CT scan control haematomas and mass effect vanished. 3. It seemed that if general and neurological condition of patients was good or improved the control could be performed in week or even longer periods of time. PMID- 1407311 TI - [Evaluation of the results of the treatment of cerebral hematoma in relation to its volume using the "best fit" method]. AB - A method is described in which the volumes of intracerebral haematomas were retrospectively measured by a method of best-fitting circles, in 173 consecutive patients. 173 patients were operated on and 41 were treated conservatively. Prognosis in supratentorial haematomas of the volume up to 65 ml is better by 20% when they are treated conservatively. It seems that surgical treatment should be reserved for patients with haematomas over 65 ml presenting progressive deterioration of neurological condition. On the other hand, patients with infratentorial haematoma over 14 ml of volume should be operated on as quickly as possible. PMID- 1407312 TI - [Acute subdural hematoma treated at the Department of Neurosurgery of the District Hospital No. 2 in Rzeszow 1976-1990]. AB - The results of the treatment of 95 patients with acute subdural haematoma with discussion of the diagnostic difficulties and method of surgical treatment are presented. The relationship between trauma severity and therapeutic results, and between alcohol abuse and higher mortality is analysed. PMID- 1407313 TI - [Results of surgical treatment of intracranial aneurysms]. AB - In the years 1986-1990 in the Department of Neurosurgery Military Hospital in Bydgoszcz 61 patients were treated surgically for intracranial aneurysms. Good results were obtained in 60.7% of cases and bad in 21.3%. Death from extracranial causes occurred in 6 cases. The number of past bleedings from the aneurysms, the clinical state of the patients, the timing of the operation, intraoperative rupture of the aneurysms were factors having a significant unfavourable influence on the early postoperative results. PMID- 1407314 TI - [Immediate and late results of the treatment of cerebrospinal rhinorrhea at the Department of Neurosurgery of the District Hospital in Rzeszow]. AB - In the period 1976-1989 in the Neurosurgery Department, Province Hospital in Rzeszow 130 patients were treated for CSF rhinorrhoea and 104 of them were treated surgically. Out of these 104 patients 6 died after the operation because of purulent complications and severe brain injury following extensive open fractures of the anterior cranial fossa. The follow-up examinations are performed 1 to 13 years after the operation and conservative treatment. From the surgical group 77 (79%) came for the examination: 75 led active life, 50 resumed occupational work, 25 had disability pensions, 2 died, the cause of death was not established. From the group treated conservatively 15 patients responded (71%). Seven resumed occupation, 8 received disability pension, one died of cerebral abscess 3 years after head trauma. PMID- 1407315 TI - [Cranioplasty of extensive defects of the cranial vault bones using a "Codubix" prosthesis]. AB - In the years 1980-1987 in the Neurosurgery Department, Medical Academy in Lodz in 21 patients aged 12 to 59 years covering of cranial vault bone defects over 100 cm2 of area was done using of cranioplasty polypropylene-polyester knitted fabric Codubix. The size of the implanted prostheses was from 100 to 430 cm2. The time from bone defect occurrence to cranioplasty was from 4 weeks to 18 years. Cranial defects resulted from treatment of trauma complications in 10 cases, treatment of intracranial tumours in 7, aneurysms in 2 and intracranial infections in 2 cases. The follow-up after cranioplasty was from 3 to 10 years. In 18 cases (85.7%) good and very good therapeutic results were obtained. Three patients required removal of prosthesis because of purulent complication, in 2 of these cases high risk of infection was present before the operation. Codubix prosthesis was particularly useful for filling giant of cranial bones. PMID- 1407316 TI - [Cranial bone prosthesis made of acrylic resins and prepared before surgical operation--description of the method]. AB - The authors present a method of cranioplasty using super-acrylate type "O". Two approaches are used to this problem--copying of the own bone of the patient and use of an appropriate prosthesis made of plastic material used in maxillofacial surgery. The obtained results were favourable with respect to cosmetic effect and clinical outcome. PMID- 1407317 TI - [Treatment of skull defects by using plastic material "Codubix"]. AB - Early and late results of surgical treatment of cranial vault defects with Codubix prosthesis in 46 cases are presented. Early after the operation purulent complications were not observed. The main problem of normal healing-in of the prostheses was at that time accumulation of subgaleal haematoma which was observed in five patients (10.8%). Late complications necessitating removal of Codubix prosthesis occurred in four cases (8.7%). In one patient Codubix treatment led to meningitis due to late cerebrospinal fluid rhinorrhoea and in the second case staphylococcal infection was diagnosed 4 month after the operation. In 2 remaining cases prosthesis became movable 5 and 21 months after operation and became depressed by several millimeters. The inquiry sent to the patients for obtaining information on their present health was answered by 70% of them, and four reported slight, stable depression of the plate. The remaining ones reported no complications. In 91% of cases the patients regarded the cosmetic effect of the operation as good and 9% as unsatisfactory. Codubix is good material for filling of bone defects. It heals in quickly, produces rarely purulent complications, but requires very careful fixation. PMID- 1407318 TI - [Use of biological vicarious biofeedback in the rehabilitation of patients with brain damage]. AB - The mechanisms of feedback not controlled by our consciousness play an essential role in the functions of the central nervous system in the process of programming of activities, behaviour and control of these functions. In case of deviations or errors of activities the possibility of their immediate correction exists. Brain damage after trauma or caused by tumour disturbs these normal feedback mechanisms producing very varying symptom complexes. In such cases it is advantageous to introduce vicarious feedback based mainly on visual and auditory afferentation. The authors present own original methods used in the rehabilitation of such patients using vicarious feedback with elbow crutch with light and sound signalling in walk learning, and platform for attitude stability exercises. The earlier obtained results of rehabilitation by this method in a large group of patients after stroke, and preliminary observations of patients after trauma and after tumour operations justify recommendation of the method. PMID- 1407319 TI - [Experience with the use of a light-guide in neurosurgical practice]. PMID- 1407320 TI - [Extensive arterial anomaly in the spinal canal (Th5-S5) in a 3-year-old boy]. AB - A case of an extensive arterial anomaly in the vertebral canal (Th5-S5) in a boy aged 3 years is described. Sudden onset of the disease with massive subarachnoid haemorrhage, loss of consciousness and signs of raised intracranial pressure suggested rather a lesion in the cranial cavity. The final diagnosis was made after myelography and spinal arteriography. In view of the extent of the lesion its radical removal was not possible. Embolization was done twice of the greatest vessels feeding the anomaly followed by decompression laminectomy. The patient is without neurological defects and pains. The case is reported in view of its rarity and atypical character of the lesion as well as its extent. PMID- 1407321 TI - [Effect of partial kyphectomy on the improvement of the results of reconstructive surgery in open meningomyelocele]. AB - The authors present the results of reconstructive surgery on an open myelomeningocele in the lumbar region, the defect being accompanied by a large skin defect and the vertebrae malformed in form of bone hump. During the surgery two vertebral bodies were removed from the top of the hump, resulting in a proper closure of the myelomeningocele. PMID- 1407322 TI - [A case of heterotopic ossification in the parapharyngeal region connected with the C2 vertebra in a 9-year-old girl]. AB - A rare case of extraskeletal ossification in the parapharyngeal region related to C2 cervical vertebra was observed in a child, without any history of trauma, inflammation or endocrinological disease. One-step surgical intervention was carried out from the side of the neck and pharynx making possible complete removal of the lesion. The girl was admitted to the hospital with dysphagia and breathing difficulties increasing in the last 6 months. During that time the child was observed in laryngological hospital departments. After the operation Horner syndrome and hypoglossal paresis developed, but presently the child is without symptoms. PMID- 1407323 TI - [Extensive bifocal location of ependymoma of the spinal cord]. AB - Spinal cord ependymomas belong to rare tumours of the central nervous system. Their malignancy is usually low although anaplastic forms are known also to occur. Surgical treatment is the method of choice supplemented often with radiotherapy. An exceptionally rare form of ependymoma with two foci of origin in the spinal cord is reported. The large extent of the tumour caused that laminectomy at 15 levels was necessary. The mechanism of ependymoma development at two levels is discussed. PMID- 1407324 TI - [Epidural hematoma with unilateral exophthalmos]. AB - A case of epidural haematoma in the fronto-temporo-parietal region with ipsilateral exophthalmus is presented. In the light of 10 cases reported in literature and one own case, and on the basis of neuroanatomical data the possible causes of this rare sign are discussed. The aetiology of this exophthalmus is still unclear and subject to discussion. PMID- 1407325 TI - [Removal of a foreign body penetrating through the orbit into the cranial cavity]. PMID- 1407326 TI - [Diagnosis and treatment of aneurysms of the lower segment of the vertebrobasilar system]. AB - The authors present 20 patients with aneurysms of the vertebral artery and its branches, treated operatively. The symptomatology and the diagnostic methods in this group of rare vascular abnormalities are discussed. The authors are of the opinion, that there are no specific symptoms typical of this localization. All aneurysms of this group can be treated by suboccipital craniectomy. The results of the operation were good; in 75% the results were good or very good. 20% patients died. PMID- 1407327 TI - [Computerized tomography in aneurysms of the posterior cranial fossa]. AB - The authors discuss the clinical usefulness of CT scan in patients with ruptured posterior fossa aneurysms. Among 164 patients after SAH, in 17 the bleeding was caused by aneurysms located in posterior fossa. The exact diagnosis of the bleeding during 5 days after SAH was possible in 94% of the patients, that is similar as in supratentorial aneurysms. The characteristic symptoms of SAH in these aneurysms was the symmetric presence of blood in basal cisterns, intraventricular haemorrhage and, in consequence,--hydrocephalus. Aneurysms of bifurcation of BA were characterized by presence of blood in interpeduncular cistern; this phenomenon was not observed in PICA aneurysms. The aneurysms of BA were more often seen in direct CT-Scan. PMID- 1407328 TI - [Spontaneous subarachnoid hemorrhage in pregnancy]. AB - Subarachnoid haemorrhage from an intracranial aneurysm or arteriovenous malformation is a grave complication of pregnancy. The authors analyzed 11 cases of verified subarachnoid haemorrhage during pregnancy from 10 identified and 1 unidentified cerebral vascular malformation. The aneurysms were responsible for subarachnoid haemorrhage in 6, and arteriovenous malformation in 4 patients. We conclude that the decision to operate after subarachnoid haemorrhage during pregnancy should be based upon neurosurgical principles, whereas cesarean delivery should be done in every pregnant patient with subarachnoid haemorrhage. PMID- 1407329 TI - [[Microsurgical treatment of cerebral hemangioma]. AB - The authors present the results of microsurgical treatment of 16 patients with intracranial arteriovenous malformations. The applied technique made possible considerable sparing of healthy brain tissue and closing feeders closely to haemangioma. The patients in I to III degree according to Spetzler's scale left the hospital in good condition. The patients in IV and V degree in 4 cases were operated on twice and in control examination have presented mild neurological dysfunction. Severe disability was observed only in 1 patient. Control angiography revealed in 3 of these patients the presence of small parts of haemangioma. PMID- 1407330 TI - [Our method of creating experimental aneurysms and its use in the training in microsurgical operations]. AB - An original method is presented used for production of experimental aneurysms in rats. The method may be useful in training for microneurosurgical treatment of aneurysms. PMID- 1407331 TI - [Anatomy of the middle cerebral artery and the angiographic image of its aneurysms]. AB - The study is based on conclusions drawn from the microanatomical analysis of 200 middle cerebral arteries and angiographic findings in 40 aneurysms of the artery. The angiograms were analysed considering the site of the aneurysm with respect to the division of the artery at the limen insulae and presence of early temporal arteries. Correlating these data with the anatomical observations, especially with regard to the site of origin of the perforating arteries it was tried to define more strictly the facts relevant to the operation which can be obtained by angiography. PMID- 1407332 TI - [Rare variants of the middle cerebral artery]. PMID- 1407333 TI - [Cerebral ischemia in young patients]. AB - The clinical, angiographic and computed tomography (CT) examinations of 19 patients aged from 12 to 30 years with signs of ischaemic brain syndrome are presented. On the basis of these examinations and data obtained from literature it is supposed that in a majority of patients the disease is caused by basal arteriopathies + i.e. pathological changes in the wall of cerebral arteries, mainly of the circulus Willis. The features distinguishing this syndrome from ischaemic disease in adults are presented and discussed. These are first of all: sudden onset connected with physical effort, deep neurological deficit, narrowing or occlusion of basal cerebral arteries seen in angiography and signs of ischaemia within deep cerebral structures visible in CT. The methods of treatment are discussed, mainly STA-MCA anastomosis used in most cases. The results of treatment are discussed. Finally the problem of the cerebral ischaemic syndrome in young people is presented from the point of view of haemodynamics, principally in the aspect of haemodynamic reserve of cerebral blood flow. PMID- 1407334 TI - [Transfontanellar USG examination using a color Doppler method in the diagnosis and differentiation of vascular changes in the CNS (preliminary report)]. AB - In the light of own experiences the diagnostic possibilities are presented of using Doppler ultrasonography with transfontanellar projection in the diagnosis and differentiation of vascular changes. Colour Doppler USG makes possible recording and measurement of blood flow in the vessels and may be specially useful in cases of central nervous lesions. The paper is supplemented with a videographic record of Galen's vein aneurysm imaged by Doppler USG. PMID- 1407335 TI - [History of the Neurosurgery Department of the Merged District Hospital in Rzeszow]. PMID- 1407336 TI - [Results of combined treatment of neoplasms of the posterior cranial fossa in children]. AB - The effectiveness of combined treatment of posterior fossa tumours was analysed using the clinical material of a neurosurgery department. The material comprised 242 patients treated in the years 1980-1987 with 211 suboccipital craniotomies performed. In cases of cerebellar astrocytoma one-year survival rate was 9% and five year survival in 89% of cases. In the group of medulloblastoma treated in the period 1980-1982 the one-year survival rate was 75%, three-year 39% and five year 25%. In the group treated in the years 1985-1987 the one-year survival rate was 95% and three-year was 60%. In ependymoma cases the one-year rate was 90%, three-year was 40% and five-year--33%. The use of combined treatment in cases of ependymoma and medulloblastoma improved significantly the therapeutic results. PMID- 1407337 TI - [New headache classification of the International Headache Society and its significance]. PMID- 1407338 TI - [Clinical application of phase contrast angiography]. AB - "Phase Contrast Angiography" is a new technique of Magnetic Resonance Angiography as reported by Dumoulin CL et al. Using this technique, we can obtain images of vessels (angiograms) without injection of contrast medium. We present the results of phase contrast angiography on cerebral and spinal vascular disease. We utilized the General Electric SIGNA, 1.5 tesla NMR. One hundred and ninety-one cases of cerebral and spinal vascular diseases were scanned using phase contrast angiography. Included were 90 cases of occlusive vascular disease, 16 cases of moyamoya disease, 39 cases of arteriovenous malformation, and 28 aneurysms. The phase contrast angiography uses flow encoding gradient pulses, which impart a velocity-dependent phase shift to the transverse magnetization of moving spins. The resulting image contains only information from the moving spins; while information from stationary tissue remains suppressed. In cases using 3-D angiogram, we made 32 images 6 degrees apart in their projection direction and displayed them on a video terminal. We were able to visualize occlusions of vessels, aneurysms, bypassed vessels, and abnormal vessels of arteriovenous malformations. Retrospective evaluation comparing phase contrast angiography with conventional angiography of the stenotic findings on the horizontal portion of middle cerebral arteries (64 vessels of 32 patients), resulted in a false positive ratio of 39.1%. We obtained clinically valuable results regarding the hydrodynamics of patients using "phase contrast angiography" non-invasively. These results reveal not only "anatomical" images of vessels, but also "functional" images, which are sensitive to the pattern of the blood flow. This study would strongly suggest that phase contrast angiography presents a valuable tool for the clinical diagnosis of cerebral and spinal vascular diseases. PMID- 1407339 TI - [New surgical technique for anterior cervical fusion; surgical technique for anterior cervical fusion utilizing autogenous bone graft from the cervical vertebrae]. AB - Since April, 1990, the authors have been reporting a surgical technique for anterior cervical fusion utilizing autogenous bone graft from the cervical vertebrae. This series included 53 patients (40 males and 13 females). The age ranged from 24 to 72 years with a mean of 49 years. There were 42 cases of cervical disc disease, and 11 cases of cervical disc disease with ossification of the posterior longitudinal ligament (OPLL). The patient was out of bed within two days and treated in a soft collar for 3 months. In all patients, the symptoms improved postoperatively. Postoperative X-ray showed slight anterior angulation deformity in 3 out of 53 cases (6%). The advantages of our surgical technique are as follows: 1) There are no problems related to the iliac donor site 2) The removal of posterior spur and localized OPLL is safely and easily performed. PMID- 1407340 TI - [The dura mater adjacent to the attachment of meningiomas: its enhanced MR imaging and histological findings]. AB - The dura mater adjacent to the attachment of meningiomas was enhanced on MR imaging with intravenous Gd-DTPA infusion. It was examined histologically in four patients with intracranial globoid meningiomas. Histological examination revealed that there was no tumor cell invasion within the dura mater enhanced on MR imaging, except at the point of their attachment. A layer of tumor cells was occasionally observed on the surface of the dura mater, but this was limited to within 5 mm of the tumor margin. Our electronmicroscopic observation indicated that enhancement of the dura mater adjacent to the attachment of meningiomas was caused by increased vascular permeability of the dural vessels and extended extravascular space. PMID- 1407342 TI - [An adult case of intradural lumbo-sacral lipoma]. AB - A rare case of lumbo-sacral lipoma in an adult case is reported. A 55-year-old male was admitted to the Department of Neurosurgery, Mazda Hospital, after a history of one year of urinary incontinence. Neurologically, no motor or sensory disturbance of the lower extremities was found in this patient. MRI showed a mass with high signal intensity on T2-weighted image, located between L3 to S2 vertebral segments. Metrizamide-CT scan demonstrated the outline of this hypodense mass at the same location as shown on MRI image. A L3 through L5 laminectomy was performed and the tumor was subtotally removed. Microscopic examination revealed that the tumor mass was made up of mature lipoma cells. Postoperative course of the patient was uneventful. The urinary incontinence was improved slightly. No motor or sensory deficit was found. We thought that MRI was useful for the correct diagnosis of lumbosacral lipoma. And it is best managed by operative removal of the tumor as early as possible after it is diagnosed. PMID- 1407341 TI - [Quantitative analysis of glutathione and glutathione S-transferase in human brain tumors, C6 rat glioma cells and drug resistant C6 cells]. AB - Glutathione (GSH) and Glutathione S-transferase (GST) plays an important role in the protection of cells against damage from free radicals and also influences cytotoxicity to some kinds of chemotherapeutic agents. GST comprises a group of abundant and widely distributed catalytic and binding proteins that facilitate the conjugation of GSH with the electrophilic center of a large spectrum of hydrophilic molecules. Multiple GST isozymes in mammalian tissues arise from dimeric combination of a number of distinct subunits grouped into three major classes: alpha (alpha), mu (mu), and pi (p). We report the total GST, GST-p activity and GSH content of human brain tumors, C6 rat glioma cells and drug resistant C6 cells. The values of total GST activity in 42 normal brain and brain tumors were quantitatively analyzed. Total GST activity was 92.6 +/- 25.1 units (mean +/- standard deviation) in 8 samples of normal brain tissues, 126 +/- 58.8 units in five grade II or III astrocytomas (154 +/- 63.3 units in grade II astrocytomas, 84.4 +/- 2.7 units in 2 grade III astrocytoma), 66.2 +/- 29.3 in 5 glioblastoma cases, 94.7 +/- 47.7 units in 3 metastatic tumors, 302 +/- 114 unit in 8 meningiomas and 213 +/- 90.4 units in 3 neurinomas. Differences of GST activity between glioblastomas and meningiomas, grade II or III astrocytomas and meningioma, in normal brain tissues and meningioma were statistically significant (p < 0.01). The difference between normal brain tissues and benign tumors (meningiomas and neurinomas), gliomas and benign tumors were also statistically significant (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407343 TI - [Recurrent fusiform aneurysm of the internal carotid artery; a case report]. AB - A 61-year-old woman was referred to our department on February 12, 1991, due to a fusiform aneurysm of her left internal carotid artery (ICA). She had received aneurysm surgery twice in other hospitals in the past. The first operation, in June, 1980, was for an unruptured, symptomatic left internal carotid-posterior communicating aneurysm and the aneurysm disappeared completely after the neck clipping procedure was carried out by one of the authors. In November, 1990, she suffered from subarachnoid hemorrhage with a hematoma in the left frontal lobe. A ruptured anterior communicating aneurysm was clipped in another hospital, where abnormal dilatation of the left ICA was pointed out. She was referred to our department after a ventricular peritoneal shunt operation. Though the postoperative angiogram performed in 1980 had shown complete disappearance of the left IC-PC aneurysm, it was presumed that the fusiform aneurysm which she presented at our department was recurrent because it existed in almost the same place as the aneurysm which had been clipped. It was also in contact with a clip applied in 1980. In accord with the patient's desire to receive surgery, the fusiform aneurysm was operated on directly, and it was remarkably reduced in size by dome clipping. During a clip, a Sugita booster clip was useful for preventing a slip-out of the clip applied on the aneurysmal dome. The patient was discharged about 20 days after the operation and returned to her usual life. A recurrent fusiform aneurysm of the ICA arising after the neck clipping of IC-PC aneurysm has rarely been encountered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407344 TI - [Spinal extradural angiolipoma: a case report]. AB - This 60-year-old man had been well until four years prior to admission, when he developed slowly progressive weakness of the lower extremities. On admission he was found to have a spastic paraparesis, sensory disturbance below the level of T10 and mild sphincter dysfunction. Conventional myelography and CT myelography demonstrated an epidural mass located from T5 to T8 vertebral level. MRI revealed that the epidural mass was fusiform and markedly enhanced by the contrast medium. Laminectomy was performed and a fibrous tumor red in color was subtotally removed. Histological findings were consistent with those of angiolipoma. Angiolipoma is a rare tumor in the central nervous system and is regarded as a clinical entity different from a spinal lipoma. Occurrence of angiolipoma in the central nervous system has been reported in 40 cases in the world literature. Thirty nine cases of them occurred in the spinal canal, especially in the dorsal epidural space of the thoracic region. The fusiform shape demonstrated in this case might also be characteristic of angiolipoma in this region. PMID- 1407345 TI - [A case of prolactinoma presenting with CSF rhinorrhea and CSF otorrhea during bromocriptine therapy]. AB - Cerebrospinal fluid (CSF) leakage is a rare complication of prolactinoma treated with bromocriptine (BC). BC is known to be effective for reducing the volume of a prolactinoma and for decreasing the serum level of prolactin (PRL). In cases of pituitary tumors, CSF leakage is thought to be caused by shunting between the subarachnoid and extradural spaces. We had a case presenting with CSF rhinorrhea and CSF otorrhea during BC therapy which was treated successfully. The mechanism and treatment of CSF leakage were studied. A 55-year-old woman complaining of nasal obstruction and headache was admitted to our hospital on Nov. 22, 1988. CT scan showed a huge intracranial mass lesion involving the sella and the supra sellar region and invading the sphenoid sinus and ethmoid sinus. Serum PRL level was 18,000 ng/ml. The patient was diagnosed as having an invasive prolactinoma, and BC therapy (5.0 mg per day) was instituted. Three days later, CSF rhinorrhea developed, and BC treatment discontinued; radiation therapy was started. After 36 Gy irradiation the size of the tumor was same on CT, and serum level of PRL was still high. The patient underwent trans-sphenoidal operation. The tumor was removed partially and the presumed CSF fistula was repaired. The sella and sphenoid sinus were packed with fat. BC treatment was reinstituted, and the serum PRL level decreased gradually without recurrent CSF rhinorrhea. Two weeks later the patient returned complaining of bilateral hearing disturbance. With a diagnosis of exudative otitis media she underwent bilateral tympanostomy. Immediately after tympanostomy, pulsating discharge from the middle ear was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407346 TI - [Holoprosencephaly accompanied with dysgenesis of the cerebellum]. AB - We have encountered 9 cases of holoprosencephaly, four of them with abnormalities of the posterior fossa. Three cases of semilobar type had severe cerebellar hypoplasia and a large cyst continuing to the fourth ventricle. They were diagnosed as Dandy-Walker syndrome. A case of lobar type had a relatively mild form of cerebellar hypoplasia and it was thought to be a Dandy-Walker variant. MRI was able to clarify the anatomical relationship of the intracranial construction, for example monoventricle, dorsal sac or large cyst in the posterior fossa, and it was very useful for the diagnosis of these congenital anomalies. All of them showed hydrocephalus and required treatment with ventriculoperitoneal or cyst-peritoneal shunt. With the availability of MRI, easy diagnosis of the mild forms of holoprosencephaly has been facilitated, and accompanying anomalies are also able to be diagnosed. Up to now, the structure of the posterior fossa in holoprosencephaly was thought to be normal. However, several cases of holoprosencephaly accompanied with cerebellar hypoplasia and cystic lesion of the posterior fossa, revealed by MRI or autopsy, have been reported. It was suggested that holoprosencephaly with anomalies of the posterior fossa may be less rare than has been thought, so far. PMID- 1407347 TI - [A case of asymptomatic Dandy-Walker syndrome with cerebellar hemorrhage]. AB - A case of asymptomatic Dandy-Walker syndrome (DWS) complicated by cerebellar hemorrhage is reported. A 65 year-old man was hospitalized for investigation and treatment of disturbance of consciousness. CT scan and MRI showed a large hematoma in the posterior fossa cyst. Postoperative CT scan and MRI revealed the DWS and cerebellar hemorrhage on the left side. This patient had no symptom until 65 years of age, in spite of having DWS. There has been no such case reported in the literature to our knowledge. Derangement of secretion and absorption of cerebrospinal fluid seem to have been the cause of late-onset symptoms after a long well balanced symptom-free period. PMID- 1407348 TI - [Suprasellar arachnoid cyst associated with precocious puberty: report of an operated case and review of the literature]. AB - The pathogenesis remains unknown in the majority of patients with precocious puberty, and yet infrequently such causative cerebral lesions as hypothalamic hamartomas are associated with sexual precocity. We reported a rare case of suprasellar arachnoid cyst in an infant presenting with precocious puberty, which eventually disappeared after a cyst-peritoneal shunt. It was believed that the mass effect of the arachnoid cyst upon the hypothalamus was, at least in part, responsible for development of precocious puberty. The role of surgical decompression of the cyst was also discussed. A one-year-old girl was admitted to the hospital for evaluation of genital bleeding which had persisted on and off for two months. The height, 80cm, and the weight, 12.4kg, exceeded by far the two standard deviations from the mean level of the normal population. In addition she had the development of breast tissue as classified Tanner's Stage II, and both pubic and axillary hair. The bone age by skeletal survey of the hand was rated as 3 years. Endocrinological examination showed that serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol had increased for her age, to levels equivalent to those for females at puberty. An LH-RH test revealed an excessive LH reaction. There were no definite neurological deficits. CT and MRI demonstrated the presence of a large arachnoid cyst involving the suprasellar region as well as the right middle and posterior fossa. After the patient underwent a cyst-peritoneal shunt, the cyst decreased in size and such symptoms as genital bleeding and breast growth disappeared. Serum levels of her LH and FSH also significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407349 TI - [A case of multiple myeloma with intracerebral metastasis]. AB - Compared to leukemia, malignant lymphoma and other hematogenous tumors, multiple myeloma rarely metastasizes to the central nervous system. Intracerebral metastasis without involvement of the cranium itself is rarer. We report a case of Ig-G k-type multiple myeloma with metastasis to the left frontal lobe extending to the right basal ganglia without involvement of the cranium. A 71 year-old male complained of exertional dyspnea and lumbago. His laboratory data revealed hyperproteinemia and an abnormal increase in Ig-G (6117mg/dl) in his serum. Serum protein immunoelectrophoresis revealed an IgG k-type band, and Bence Jones protein was detected in his urine. MMPP, VMCP, VIPP and MP chemotherapy was given, and serum IgG level decreased to a normal range. 21 months after his first admission, incontinence, disorientation, gait disturbance and apathy developed. CT-scan showed an isodense lesion with massive edema in the left frontal lobe and right basal ganglia. On MRI, a Gd-DTPA enhancing lesion was detected extending from the left frontal to the opposite frontal lobe through the splenium. No abnormal skull punched out lesions were noted. Left frontal lobectomy was performed. Histopathology revealed plasmablastic myeloma cells with clear nucleole and eccentric nucleus in the cerebrum. He was diagnosed as having intracerebral metastasis of multiple myeloma without involvement of the cranium. Unfortunately, he died of pancytopenia and pneumonia. Our case suggests the possibility of metastasis via blood into the cerebrum. PMID- 1407350 TI - [A case of traumatic spinal subarachnoid hematoma causing compression of the cauda equina]. AB - A case of traumatic spinal subarachnoid hematoma causing compression of the cauda equina is reported here. The patient, a 76 year-old woman, who had fallen down by accident 1 month before, was admitted to our hospital presenting lumbar pain radiating into her right thigh, monoplegia of the right leg and urinary incontinence. Myelography and metrizamide CT demonstrated a filling defect mimicking intradural extramedullary tumor at the level of L1 and L2. Magnetic resonance imagings (MRI) revealed a subacute or chronic hematoma compressing the conus medullaris and the cauda equina. Operation was performed and an old hematoma, which occupied most of the spinal subarachnoid space and compressed the conus and cauda equina from right to left, was removed. No definite bleeding point was detected and no traumatic change was seen on the cord. Neither tumor nor abnormal vessel was detected. After surgery, the symptoms improved partially. On a review of the literature, we found only 4 cases of traumatic spinal subarachnoid hematoma, all of which occupied the cervical or thoracic portion of the spine. Our case is the first report, except for the cases following lumbar spinal tap, of traumatic spinal subarachnoid hematoma causing compression of the cauda equina. Though usually blood in CSF diffuses immediately, a clot may be formed when a large amount of bleeding obstructs the spinal canal. In our case, furthermore, deformity and narrowing of the spinal canal had preceded for many years, following lumbar vertebral compressed fracture related with osteoporosis. This might have promoted the process of canal obstruction and clot formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407351 TI - [Cerebral salt wasting syndrome secondary to head injury: a case report]. AB - A case of cerebral salt wasting syndrome secondary to head injury is reported here. A 4-year-old boy was admitted to our hospital with head injury. Neurological examination revealed no abnormal findings other than consciousness disturbance. Plain skull X-ray demonstrated a linear fracture of the bilateral parietal bones, and CT scan demonstrated subarachnoid hemorrhage of the tentorium of the cerebellum. He gradually improved, but on the 6th day deterioration of consciousness developed. At that time CT scan demonstrated no abnormal findings. Biochemical analysis showed hyponatremia (116mEq/L) with increased natriuresis. Although a high dose of NaCl was supplied, serum sodium levels did not normalize. So we suspected that SIADH might be causing the hyponatremia, and water restriction was started. He lost 1 kg in body weight over 3 days, but serum sodium levels remained low (118mEq/L) with increased natriuresis. We found that the hyponatremia was caused by cerebral salt wasting syndrome, so we treated the patient with fludrocortisone acetate. Consciousness disturbance improved two days after the medication with fludrocortisone acetate, and serum sodium levels became normal (137mEq/L) on the 27th day. The administration of fludrocortisone acetate was able to be stopped two months after admission, and then the patient was discharged without any neurological deficits. We discussed in detail the diagnosis and the treatment of cerebral salt wasting syndrome. PMID- 1407352 TI - [Two cases of recurrent brain tumor during GH replacement therapy]. AB - Two cases of patients with recurrent brain tumor are presented. Each of them received growth hormone (GH) replacement therapy for growth failure secondary to cranial irradiation. The first case is that of a 10-year-old girl who was treated with a combination of surgical resection, radiotherapy and chemotherapy for cerebellar medulloblastoma at 1 y.o. At the age of 9, 10 month after the beginning of GH replacement therapy, she complained of headache. This was due to shunt malfunction when CSF cytology was class V. It revealed that there was recurrence of medulloblastoma. The second case is that of a 14-year-old girl who was treated with a combination of surgical resection, radiotherapy and chemotherapy for suprasellar germinoma at the age of 10. This tumor completely disappeared after these procedures. For her growth failure, we started GH replacement therapy and after 1 year, she complained of lt. leg pain due to tibial and pelvic bone metastasis. In medical literature, we found 15 recurrent brain tumors during GH replacement therapy. These include our 2 cases, and 9 cases in which there was recurrence within 1 year. Recently, receptors for some somatomedins have been found in brain tumors. Although these numbers are too small for us to arrive at conclusions, we think it is possible that there are some mechanisms connecting GH replacement therapy and recurrence of certain brain tumors. PMID- 1407353 TI - [Acute epidural hematoma following evacuation of chronic subdural hematoma with continuous closed system drainage]. AB - The authors report a case of acute epidural hematoma occurring after evacuation of chronic subdural hematoma with continuous closed system drainage. Laboratory data of the patient including bleeding time were within normal limits. The cause of the postoperative intracranial hematoma was the rapid surgical decompression of the initial lesion, and we considered that it could be prevented if chronic subdural hematoma was treated using closed system drainage and slow decompression. But acute epidural hematoma occurred after this operative procedure and it was accelerated by evacuation of the chronic subdural hematoma through the drain. An emergent craniotomy and removal of the hematoma was performed, so the patient was discharged from hospital with satisfactory neurological recovery. A careful check of the evacuated hematoma volume is very important, and CT scanning should be immediately performed if postoperative hematoma is suspected. PMID- 1407355 TI - [A case of Turner's syndrome associated with moyamoya disease]. AB - A case of Turner's syndrome associated with Moyamoya disease in a 10-year-old female is presented. This patient had experienced two periods of syncope and transient right hemiparesis in 2 years. She was short in stature. She had cubitus vargus and mental retardation. The serum LH and FSH values were high. By chromosomal examination Turner's syndrome (karyotype: 45, X/46, X, i(Xq)) was diagnosed. An MRI (SE 2000/20) revealed abnormal vessels on the basal ganglia. Cerebral angiography showed occlusion of bilateral internal carotid arteries at the distal portion, bilateral posterior cerebral arteries at the proximal portion. Basal moyamoya well developed. EDAS (encephalo-duro-arterio-synangiosis) was performed bilaterally. We consider that this may be the first case report of Turner's syndrome associated with Moyamoya disease, and that there may be no relationship between Turner's syndrome and Moyamoya disease in this case. PMID- 1407354 TI - [Malignant melanoma metastatic to the cavernous sinus and skull with an unknown primary origin: report of a case]. AB - A rare case of malignant melanoma metastatic to the cavernous sinus and skull, with an unknown primary origin, is reported. A 46-year-old man noticed diplopia, lt. ptosis and swelling in the parietal and maxillary regions. The parietal skull tumor and the maxillary lymph node were excised and histological examination revealed malignant melanoma. Because of its roentogenological characteristics, the lesion of the cavernous sinus was also thought to be the site of metastasis of malignant melanoma. This case is rare because the initial symptom was cavernous sinus syndrome, and no involvement of brain parenchyma was observed. PMID- 1407356 TI - [A case of intracranial multiple nonspecific granulomas related to rheumatic disease: with special reference to magnetic resonance imaging]. AB - We encountered a rare case of a 48-year-old man with intracranial multiple granulomas secondarily caused by rheumatic disease. This was proven surgically after an 11-year course of remissions and deteriorations. In 1980, at the age of 32 years, the patient was first seen at the clinic of Neurology of the University Hospital, complaining of swelling and arthralgia of the joints of the knee, ankle, and wrist and with remittent fever and visual disturbance. The patient was diagnosed as having possible rheumatoid arthritis, and treated with administration of 30mg/day of prednisolone, which greatly improved the symptoms. The administration of 5 to 10mg/day of prednisolone had been continued after discharge from hospital. In 1985, visual acuity of the left eye decreased, and left facial hypesthesia developed. The patient was rehospitalized at the same clinic, and treated with 100mg/day of prednisolone, which again diminished the symptoms. Computed tomography(CT) on admission showed a high density mass with contrast enhancement in the left cavernous region. In addition to the left cavernous mass, a high density mass was detected by CT in the left parietal lobe, in 1987. Visual acuity of the left eye deteriorated in 1989. Because his response to prednisolone had decreased, the visual symptom was treated with gold sodium, which acted effectiveness. Symptoms deteriorated again in 1990. Early in 1991, CT and magnetic resonance imaging showed a new mass at the right frontal lobe, while the mass in the left cavernous region had increased in size. The patient was transferred to the clinic of Neurosurgery for surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407357 TI - [Natural history for residual intracranial AVM: compared with that for conservatively treated AVM]. AB - It is generally accepted that the most suitable treatment of AVM is surgical removal which does not cause neurological deficits. But in some cases, it is impossible to treat surgically because of size or location, so the patient is unfortunately discharged with some part of the nidus remaining. In this paper, we report the natural history of residual AVMs in which part of the nidus remained after initial therapy, and try to ascertain whether therapeutic reduction of the nidus is more effective in preventing intracranial hemorrhage than conservative treatment. Of 362 cases, residual AVMs were found in 35 cases, and were followed up for 9.2 years on average. Eighty cases treated with only conservative therapy were also followed up for 10.9 years on average. The annual risk of intracranial hemorrhage for residual AVMs was 2.9% and that for conservatively treated AVMs was 3.0%, not a significant difference. There was no difference between the two groups in mortality or ADL. We conclude that therapeutic reduction of the nidus was not effective in preventing intracranial hemorrhage. PMID- 1407358 TI - [Effects of gamma-hydroxybutyrate on monoamine metabolism and protein synthesis after transient global cerebral ischemia]. AB - The effects of gamma-hydroxybutyrate (GHB) on 1) monoamine metabolism, and 2) protein synthesis were examined in a gerbil stroke model. The monoamine metabolism was studied by occluding bilateral common carotid arteries for 15 minutes followed by GHB administered intravenously 3 hours later. Tissue monoamine concentration was examined up to 8 hours after recirculation. Three hours after GHB administration, dopamine (DA) had increased to almost twice that of the non-treated group, whereas homovanillic acid, a metabolite of DA, did not show any significant difference. These results may mean that GHB will facilitate DA synthesis but that it has no influence on its release. Therefore, a DA mediated increase in cerebral blood flow in the cerebral cortex cannot be expected. Tryptophan, a precursor of 5-hydroxytryptamine (5HT), started to increase just after recirculation reaching a level of over four times that of the control value at 2 to 3 hours, and then starting to decrease in the non-treated group. This decline in tryptophan was markedly facilitated by GHB administration within 1 hour. On the other hand, 5HT administration within 1 hour. On the other hand, 5HT increased only very slightly in the cerebral cortex 1 hour after GHB administration, the change ratio being 1/30 of tryptophan. It can therefore be speculated, that the decrease in tryptophan brought about by GHB administration is due to the improvement in disturbed protein synthesis rather than to stimulation of 5HT synthesis. Protein synthesis was studied by administering GHB 2 minutes prior to a 5-minute temporal common carotid artery occlusion. Ninety minutes after recirculation animals were given a single dose of 14C-leucine and further 60 minutes were allowed to pass before sacrifice. Autoradiographs of the GHB-treated group were compared with those of the non-treated group. With GHB pretreatment, autoradiographs showed an increased uptake of 14C-leucine in at least the hippocampus, thalamus, and hypothalamus, and in two out of three animals, there was diffusely increased uptake. Thus, it is speculated that GHB is effective in improving the protein synthesis in the postischemic period. The favorable function of GHB during cerebral ischemia is regarded by many to be prevention of energy failure by reducing cerebral metabolism. On the other hand, the results derived from the present study suggest that GHB may improve protein synthesis in the postischemic period. Thus, we suggest that GHB is useful if given at the acute stage of cerebral ischemia such as during internal carotid artery or middle cerebral artery occlusion. PMID- 1407359 TI - [Electrophysiological identification of the cochlear and vestibular nerves in the cerebellopontine angle: experimental study and clinical implication]. AB - Electrical stimulation was applied on the surface of the eighth cranial nerve in the cerebellopontine angle of dogs and the evoked potentials were recorded with surface electrodes on the scalp. The shape of the evoked potentials recorded was different according to the portion of the nerve stimulated electrically. It was, therefore, possible to precisely identify the nerve stimulated from the surface recorded evoked potentials. This electrophysiological method may be helpful for the surgeon to precisely locate the cochlear and vestibular nerves in various operations in the cerebellopontine angle in human. Our preliminary experience of this monitoring method in acoustic neuroma excision was presented. PMID- 1407360 TI - [Long-term prognosis of nonoperative acute epidural hematoma in children]. AB - Computed tomography(CT) scan has revealed that certain acute epidural hematomas(AEH) don't need operative therapies. But, it is difficult to determine especially in childhood, whether AEH compressing the brain for a short-term would or would not effect the function of the central nervous system in the future. For this reason, the authors report the long-term prognosis of nonoperative AEH in children. Twelve children suffering from AEH were transported to our clinic. On admission, they had no neurological deficits and CT scan revealed hematomas that had maximum thickness of 5-19 mm without midline shift. With nonoperative therapy they were discharged and the hematomas disappeared within 3-12 weeks. After long term follow-up (3-10 years), it was shown that they had no epileptic episodes, and no changes in their school study records. Also, the Yatabe-Guilford personality test revealed no abnormal data. These data suggest that children can be cured who suffer from AEH with no neural deficits, and in whom the maximum thickness of the AEH is less than 20 mm, and in whom there is no midline shift in CT scan, can be cured without undergoing an operation, and will have a good long term prognosis. PMID- 1407361 TI - [Analysis of long-term social rehabilitation of brain contusion]. AB - 164 patients with brain contusion were evaluated with respect to social rehabilitation. 70 out of 134 patients (66.7%), said to have had good recovery or moderate disability by the Glasgow Outcome Scale (GOS), returned to full or partial employment. Factors such as age, Glasgow Coma Scale (GCS) at admission, duration of unawareness, fibrin and fibrinogen degradation product (FDP) were the most important in predicting social recovery. The Wechsler Adult Intelligence Scale (WAIS) was applied in 33 patients. The IQs of the patients who returned to their job fully tended to be higher than those who could not. In the majority of patients, impaired capacity for work was caused not only by physical deficits, but by mental retardation described as such as IQ score. PMID- 1407363 TI - [Traumatic intracranial aneurysms after removal of tuberculum sellae meningioma: case report]. AB - Two cases of traumatic aneurysms (TA) of the internal carotid artery (IC) due to removal of tuberculum sellae meningioma (TSM) are presented, and ideal treatment of those aneurysms is discussed. The tumor, compressing the IC laterally, was removed out without arterial injury in case 1. Though the patient's postoperative course was uneventful, frontal and intraventricular hemorrhage developed 2 months after the operation, and an IC dorsal aneurysm was detected. Preoperative angiograms showed no aneurysm, so it was considered to be a traumatic aneurysm due to the surgical procedure. The aneurysm was clipped at once, but postoperative angiograms showed recurrence of the aneurysm. IC balloon occlusion was carried out as the Matas test was negative. In case 2, a small tear in the IC was inadvertently made during recurrent TSM removal, which was wrapped with muscle using fibrin glue. 2 weeks after the operation, frontal hemorrhage developed. Angiograms revealed a small aneurysm of the IC, which was considered to be a traumatic aneurysm. IC balloon occlusion was performed as the Matas test was negative. These 2 patients have had no episodes of rerupture after the IC balloon occlusion. Tumors and main arteries are frequently adhesive, so arteries are easily injured during removal of meningiomas. Muscle wrapping was not enough to prevent TA formation. Neck clipping was not appropriate for treatment of TA, but IC balloon occlusion was an effective and excellent therapy for TA of IC. PMID- 1407362 TI - [Pitfalls of endovascular treatment for cerebral aneurysms]. AB - Seventeen cases of unclippable aneurysms were treated by the endovascular balloon technique. Nine of them involved the anterior circulation, and eight involved the posterior circulation. Eleven of them were treated by parent artery occlusion with detachable balloons. Three were treated by endosaccular balloon embolization, and three cases combined with AVMs were occluded using ethylene vinyl alcohol copolymer (EVAL) including feeding arteries of the AVMs. Embolic complications occurred in one case of an IC bifurcation giant aneurysm treated by parent artery occlusion. Ischemic complications also appeared in two cases of aneurysms treated by endosaccular balloon embolization. In one case, the thrombus in the aneurysm propagated into the parent artery and occluded it later. In another case, the displaced balloon had obliterated the parent artery 6 hours after the embolization. Parent artery occlusion is a safe way to treat internal carotid giant aneurysms. However, endosaccular treatment still has some problems, i.e., 1) maintaining the balloon's position to preserve the parent artery, 2) balloon migration into the clot, 3) rupture of the aneurysm during or after treatment. Our studies indicate that endosaccular balloon embolization is still a high risk procedure and should be used only in selected cases, until new embolic agents, such as detachable coils, become available. PMID- 1407364 TI - [A report of four cases of intrathoracic meningocele]. AB - Intrathoracic meningocele is regarded as an uncommon pathological entity frequently associated with von Recklinghausen's disease. In this paper, four cases of intrathoracic meningocele, treated between 1966 and 1986, are presented. There were three males and one female, all between the ages of 40 and 50. These were referred to our clinic for further evaluation of an asymptomatic lesion which had been seen on a routine chest roentgenogram. There was definite evidence of von Recklinghausen's disease in three cases: two males and one female. All four cases had no pain, dyspnea or neurological disorder. Chest and vertebral tomograms revealed masses in the posterior mediastinum and enlarged vertebral canals at the location of the lesion which varied from T-3 to T-11; three on the left side and one on the right side. None of them revealed scoliosis or kyphosis of the spine. In three cases, myelography was performed and showed an egg-shaped mass dorsolaterally. In two cases, metrizamide computed tomographic myelography was carried out and demonstrated deformity of the vertebral bone and passage of the contrast material through the enlarged vertebral canal into the paravertebral mass. Furthermore, magnetic resonance imaging was performed in two cases, and showed a homogeneous low signal intensity paravertebral mass communicating with the spinal canal on T1-weighted image. In two cases, the meningoceles were ligated or wrapped surgically. Postoperatively one presented a paraparesis and severe meningitis, and died; the other had an uneventful postoperative course. Two patients were followed conservatively without developing any symptoms or signs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407365 TI - [A ruptured aneurysm at the peripheral collateral circulation of the anterior choroidal artery in a patient with moyamoya disease: a case report]. AB - This 42-year-old man experienced a sudden onset of occipital headache. Neurological examination revealed a moderately disturbed consciousness and a moderate left hemiparesis. CT scan disclosed a hugh hematoma in the right temporo parietal lobe without intraventricular hemorrhage. A cerebral angiography demonstrated typical findings of moyamoya disease and a small saccular aneurysm at the peripheral portion of the right anterior choroidal artery, which was dilated at the collateral circulation to the parietal lobe. The hematoma was removed at once by a craniotomy. He became alert but mild hemiparesis persisted. MRI disclosed a small signal-void lesion lateral to the trigone of the right lateral ventricle. The angiography repeated three weeks after the removal of the hematoma showed the unchanged size of the aneurysm. Direct surgery for the aneurysm was performed via the right parietal transcortical approach. The aneurysm was reached under the guidance of the intraoperative angiography. Trapping of the parent artery and the excision of the aneurysm were performed. On the basis of the presence of an internal elastic lamina at the neck of the aneurysm, the surgical specimen was histologically verified to be a true aneurysm. Since the collateral circulation was well preserved during surgery, no worsening of the neurological manifestation was observed. In view of the unfavorable prognosis for a moyamoya patient with this type of the aneurysm, which often results in a massive ventricular or intracerebral hemorrhage, surgery directed to the aneurysm itself should be considered. PMID- 1407366 TI - [Penetrating injury of the common carotid artery: report of a case]. AB - An eighty-year-old man slipped in the bathroom and received a deep slash wound in his left neck caused by a broken fragment of the bathroom door. A fragment of the glass stuck into his left neck. He was carried to our clinic after 20 minutes in a state of shock and showed right hemiparesis and aphasia. Following immediate orotracheal intubation and emergent therapy for shock, he was transferred to the operation theater for massive arterial bleeding from the wound. The left common carotid artery and internal jugular vein were exposed by extending the skin incision from the cervical wound along the anterior border of the left sternocleidomastoideus. The left common carotid artery and the internal jugular vein were simultaneously transected, and end-to-end anastomosis of the carotid artery was performed under the administration of 300 ml of Sendai Cocktail. The occlusion time of the left common carotid artery was approximately 50 minutes. Right hemiparesis and total aphasia did not change immediately after the surgery. The postsurgical CT scan showed an infarction in the posterior portion of the left middle and posterior cerebral arteries. However, after undergoing rehabilitation for a month, the patient could walk alone, and his aphasia improved. Many large series of penetrating injuries to the carotid artery were reported after World War II. Most casualties were younger males injured by gunshot. In middle cervical injury, the common carotid artery is the most vulnerable vessel, although other large vessels such as the external and internal carotid arteries as well as the internal jugular vein may be involved, often causing neurological deficits and shock.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407367 TI - [Multiple cerebral infarction by blood-borne tumor emboli in carcinoma of the mid pharynx: an autopsy case]. AB - In May, 1989, a-54-year old man was admitted complaining of sore throat and tumor of the neck which had persisted for 2 months. Mid-pharyngeal tumor was diagnosed as poorly differentiated squamous cell carcinoma (stage, T3N2M0) and the patient was treated with radiation (Co 65Gy) from May 30 to July 24 and chemotherapy (UFT), which therapies were effective. On Aug. 16, sudden onset of consciousness disturbance and hemiparesis was revealed, and MRI showed small cerebral infarction. He died on Oct. 23, of pneumonia. Pathological diagnosis revealed a case of carcinoma of the mid-pharynx with wide-spread tumor embolism. Multiple cerebral and myocardial infarctions, thrombus in pulmonary arteries and congestion of kidneys with tumor emboli, due to "disseminated intravascular carcinomatosis" were noticed. A direct cause of death was dyspnea due to multiple lung metastases, pneumonia and tumor embolism in the pulmonary and coronary arteries. PMID- 1407368 TI - Diencephalic GABAergic neurons in vitro respond to prolactin with a rapid increase in intracellular free calcium. AB - In order to analyze the feedback action of prolactin (PRL) on the hypothalamus on the cellular level, we used primary cultures of rat embryonic diencephalon to measure the calcium response of individual neurons to PRL by means of fast fluorescence photometry. The cultures were subsequently stained with antibodies against the neuronal marker MAP-2, glutamic acid decarboxylase (GAD) or tyrosine hydroxylase (TH). PRL caused a rapid rise of intracellular free Ca2+ in a specific type of GABAergic neuron characterized by a spindle-shaped bipolar morphology and immunoreactivity to MAP-2 and GAD but not to TH. It is concluded that a subpopulation of hypothalamic GABAergic but not dopaminergic neurons react to PRL with a rapid increase in intracellular free Ca2+. These data are compatible with the assumption of a rapid negative feedback regulation of the secretion of PRL from the pituitary mediated by tuberoinfundibular GABAergic neurons. PMID- 1407369 TI - Centrally administered insulin-like growth factor II fails to alter pulsatile growth hormone secretion or food intake. AB - Insulin-like growth factor II (IGF-II) peptide, mRNA, and receptors are widely distributed in the central nervous system, yet the physiological role of IGF-II in brain remains largely unknown. In the present study, we examined the in vivo effects of central administration of recombinant human IGF-II on pulsatile GH secretion and food intake. The IGF-II preparation used was shown to stimulate 3H thymidine incorporation in MG-63 human osteosarcoma cells in vitro. Free-moving adult male rats bearing chronic intracerebroventricular (icv) and intracardiac venous cannulae were icv administered 10 microliters of either IGF-II (in doses of 300 ng and 1 microgram) or the vehicle solution, and blood samples were obtained every 15 min for 6 h. Vehicle-injected control animals exhibited the typical pulsatile pattern of GH secretion with most peak GH values greater than 100 ng/ml and trough levels less than 1.2 ng/ml. Central administration of IGF II, at both doses, failed to alter the spontaneous 6-hour GH secretory profile; there were no significant differences in either GH peak amplitude, GH trough level, GH interpeak interval, or mean 6-hour plasma GH level, compared to vehicle injected controls. There was also no effect of icv administered IGF-II on mean plasma glucose or insulin levels. Compared to vehicle-injected control rats, the icv injection of IGF-II (at doses of 300 ng and 1 microgram) did not significantly alter 24-h food intake or body weight gain in normal feeding rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407370 TI - Angiotensin II receptor development in the bed nucleus of the stria terminalis and other perihypothalamic brain regions of the female and male rat. AB - Brain angiotensin II (AII) receptors play a role in the regulation of luteinizing hormone release. This action is thought to involve luteinizing hormone-releasing hormone containing neurons in the preoptic-anterior hypothalamic (POAH) area of the brain. Previous studies have demonstrated a discrete locus of AII receptor binding sites and responsiveness within the POAH to microinjections of AII in the adult female rat, corresponding to the ventral portion of the bed nucleus of the stria terminalis (BSTV). To further characterize the age- and sex-dependent AII receptor binding in the BSTV and other brain regions, in vitro receptor autoradiography using 125I-sarcosine1, isoleucine8 AII (125I-SI AII) was performed on 2-, 4- and 10-week-old female and male rat brains. Rats of both sexes displayed an age-dependent increase in 125I-SI AII binding in the BSTV, as well as in the suprachiasmatic nucleus (SCh). There was no detectable difference in binding within the BSTV between the female and male of any age group. Prepubertal ovariectomy did not impair the expression of 125I-SI AII binding in the BSTV or the SCh of adult female rats. The developmental expression of AII receptors in the BSTV and SCh may therefore play a role in sexual maturation and regulation of sexual function in the rat. PMID- 1407371 TI - Pro-opiomelanocortin-containing neurons in rat median eminence. AB - A significant number of pro-opiomelanocortin (POMC)-containing cells were detected in the rat median eminence (ME) by immunocytochemistry using an antibody raised against a synthetic peptide corresponding to the cleavage site between adrenocorticotropin and beta-lipotropin moieties. Distribution of POMC-positive cells was restricted to the internal zone of the anterior parts of the ME. Such cells were observed as early as the 14th day of gestation in the area of the primitive ME, long before glial fibrillary acidic protein-positive cells appeared postnatally in this structure. Dissociated cell cultures obtained from the ME of 1-day-old rats produced cells immunoreactive for neurofilaments and the POMC moiety. Such cells displayed a neuronal morphology: the cell body was oval (13-18 microns) with long and fine beaded fibers. These findings clearly demonstrate the early appearance of POMC neurons in the developmental ME, a target organ of the hypothalamic infundibular neurons. PMID- 1407372 TI - Stimulation of prolactin secretion from rat pituitary by luteinizing hormone releasing hormone: evidence against mediation by angiotensin II acting through a (Sar1-Ala8)-angiotensin II-sensitive receptor. AB - In aggregate cell cultures of 15- to 20-day-old rat pituitary maintained in serum free medium, luteinizing hormone-releasing hormone (LHRH) (10 nM) stimulated prolactin (PRL) release, confirming our previous results and those of others with serum-supplemented medium. Since angiotensin II (AII) stimulates PRL release and a renin-angiotensin system is expressed in gonadotrophs, LHRH stimulation of PRL release might be mediated by AII. To evaluate this hypothesis, the influence of (Sar1,Ala8)AII and (Sar1,Ile8)AII two peptide AII receptor antagonists, of DUP753, a nonpeptide and stable AII receptor antagonist, of a converting enzyme inhibitor, and of angiotensinogen on LHRH-induced PRL release was tested in various in vitro conditions of 15- to 20-day-old female rat pituitary. In aggregates maintained in serum-free medium with or without dexamethasone (DEX) and triiodothyronine (T3), or maintained in serum-supplemented medium, the effect of LHRH on PRL release was not affected by (Sar1Ala8)AII (0.1 microM), (Sar1,Ile8)AII (10 microM) or DUP753 (10 microM). Only a high dose (10 microM) of (Sar1,Ala8)AII attenuated the LHRH-induced PRL release. The latter attenuation was seen only with aggregates cultured in the DEX/T3 medium and not with aggregates cultured in the presence of serum. A dose of 1 or 10 nM (Sar1,Ala8)AII also failed to block the effect of LHRH used at 1 nM. In contrast, (Sar1,Ala8)AII dose dependently as well as DUP753 (10 microM) abolished the AII-induced PRL release. (Sar1,Ala8)AII also failed to affect the LHRH-induced PRL release in pituitary cell aggregates from 6-week-old male rats. However, in aggregates from both immature and 6-week-old rats, (Sar1,Ala8)AII provoked a small and statistically significant attenuation of the LHRH-induced PRL release when a 100 nM dose of LHRH was used. In freshly isolated hemipituitaries from 5-day-old rats, (Sar1,Ala8)AII (1 or 10 microM) did not affect the LHRH- (10 nM) induced PRL release. In single cells obtained by redispersion of aggregates and mounted in a Biogel P2 column, LHRH still stimulated PRL release. Again this effect could not be blocked by DUP753. Treatment of aggregate cell cultures with the angiotensin-converting enzyme inhibitor captopril or with angiotensinogen did not alter the LHRH-induced PRL release. It is concluded that AII is not the paracrine factor mediating the effect of LHRH at low nanomolar doses on PRL release, at least not through the classical AII receptor. The involvement of AII acting on a non-(Sar1,Ala8)AII-sensitive receptor cannot be excluded and warrants further investigation. PMID- 1407373 TI - Opiate stimulation of prolactin secretion is reversed by ovarian hormone treatment. AB - Previous studies have indicated that during the estradiol- and progesterone (P4) induced surge in luteinizing hormone (LH), the effects of opiates on behavioral, autonomic and neuroendocrine functions are altered. In the present study, we further evaluated the apparent universality of alterations in opiate-mediated function during the LH surge by investigating the effects of morphine sulfate (MS) on prolactin (PRL) secretion during both the estradiol benzoate (EB) and the EB + P4-induced LH surges. All doses of MS tested (0.5, 2.0 and 5.0 mg/kg) resulted in significant increases in PRL secretion in nonestrogen-treated animals which did not show LH/PRL surges. During the LH/PRL surge induced by EB/P4 treatment, MS caused no change in the PRL secretion, while in EB/oil treated animals, a paradoxical and dose-dependent decrease in PRL secretion was observed. The suppression of PRL was 52, 68 and 80% of baseline respectively for the 3 doses of MS. Evaluation of the time dependence of MS on PRL secretion showed that the paradoxical suppression in EB/oil-treated animals was seen only during the LH/PRL surge, occurring at 17.30 h (7.5 h post P4 injection), and not before (12.30 h) or after (23.00 h) the steroid-induced LH/PRL surge. Finally, we assessed the role of pituitary dopamine receptors on the phenomenon of MS-induced PRL suppression in EB/oil rats. Domperidone (1mg/kg), a peripherally active D2 receptor antagonist, administered prior to the morphine challenge, attenuated the opiate-induced PRL suppression in EB/oil-treated animals suggesting that a dopaminergic mechanism is involved in this paradoxical response to morphine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407374 TI - Alterations in brain atrial natriuretic polypeptide levels in hypophysectomized rats. AB - Twelve days after hypophysectomy depleted atrial natriuretic polypeptide (ANP) concentrations were measured in the plasma and in 8 of 18 microdissected brain nuclei of rats. Reduced ANP levels were found in brain structures (subfornical organ, organum vasculosum laminae terminalis, preoptic and hypothalamic periventricular nuclei, paraventricular nucleus, lateral hypothalamic area), which are directly involved in the central regulations of salt and fluid homeostasis, as well as in the medial amygdaloid nucleus and the locus ceruleus. ANP concentrations in the median eminence, medial preoptic and arcuate nuclei did not alter by hypophysectomy. Elevated ANP concentrations were measured only in the supraoptic nucleus of hypophysectomized rats. PMID- 1407375 TI - Effects of sex and age on pyridostigmine potentiation of growth hormone-releasing hormone-induced growth hormone release. AB - Previous studies have shown that pyridostigmine (PD) is capable of increasing the growth hormone (GH) response to GH-releasing hormone (GHRH) in young healthy subjects. In order to investigate the influence of age and sex on the PD potentiation of GHRH-induced GH release, we have studied the GH response to GHRH (50 micrograms i.v.) 1 h after oral administration of placebo or PD (60 mg) in 8 young healthy men (aged 19-28 years) and 8 age-matched young women (aged 18-25 years) during the follicular phase of the menstrual cycle, as well as in 8 postmenopausal women (aged 57-62 years) and 8 age-matched elderly men (aged 56-64 years). In the same subjects the effect of PD alone (60 mg p.o.) was also studied. Furthermore, in 6 postmenopausal women and 6 elderly men, the effect of a 30-mg PD oral dose on GH secretion and GH response to GHRH was evaluated with a similar protocol. The GH responses (mean +/- SE) to GHRH + placebo were similar in young men (peak 20.1 +/- 2 ng/ml, AUC 1,250 +/- 113 ng/ml/min) and women (peak 29.3 +/- 2.3 ng/ml, AUC 1,769 +/- 305 ng/ml/min). PD 60 mg was capable of significantly increasing the GH response to GHRH in young men (peak 43.5 +/- 5.1 ng/ml, AUC 3,734 +/- 472 ng/ml/min, p less than 0.005) but not in women (peak 39 +/- 2.3 ng/ml, AUC 2,479 +/- 205 ng/ml/min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407376 TI - Inhibin/activin subunits are costored with FSH and LH in secretory granules of the rat anterior pituitary gland. AB - We recently reported that pituitary gonadotropes, major targets of circulating inhibins and activins, are also capable of synthesizing the inhibin (I) alpha- and inhibin/activin (I/A) beta B-subunits. In the present study, we examined the subcellular distribution of these subunits, with special attention given to determinating the extent to which they might be colocalized with the gonadotropins in secretory granules. Pituitaries from adult male rats were cryofixed, molecular distillation-dried, and resin-embedded. Immunogold staining methods were used to examine concurrently the distributions of an I/A subunit and FSH or LH. I/A subunits were detected only in cells that also labeled positively for a gonadotropin, and, in contrast to the gonadotropins, were sequestered almost exclusively within secretory granules. The I alpha-subunit colocalized with FSH in 31%, and with LH in 36%, of all positively stained granules. The I/A beta B-subunit was found with FSH or LH in about 25% of the granules. Approximately 52-69% of the granules contained FSH or LH alone; 7-18% were positive only for an I/A subunit, and this varied as a function of the particular gonadotropin with which costaining was carried out. Dual staining for the I alpha and the I/A beta B-subunits indicated that at least 35% of all immunolabeled granules showed positive signals for both subunits. Coupled with methodological considerations to indicate that these estimates of the extent of colocalization are likely to be conservative, these data suggest that inhibin and activin are characteristically copackaged, and presumably coreleased, with the gonadotropins. PMID- 1407377 TI - Characterization of prolactin receptors in human choroid plexus. AB - The specific binding of 125I-human prolactin (hPRL) was studied in different areas of the human brain. Particularly high binding affinity of the hormone was found in the choroid plexus and this tissue was therefore selected for further studies. The hippocampus, the hypothalamus and the pituitary were among other regions containing prolactin-binding sites. In the choroid plexus the amount of PRL receptors was significantly higher in females than in males and was also found in both sexes to decrease with age. The binding affinity of 125I-hPRL to choroid plexus was 3.0 x 10(9) M-1 and the binding capacity was 10.3 pmol per mg protein. Following solubilization with Triton X-100 the PRL receptor fraction retained its hormone-binding properties and upon molecular sieve chromatography it behaved as a protein with a molecular mass of approximately 250,000. Cross linking of 125I-hPRL to receptors from choroid plexus and subsequent sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis indicated a major hormone-binding unit of M(r) 44,000. This value is about 7,000 smaller than that reported earlier by us for the growth hormone receptors from the same tissue, following cross-linking to 125I-human growth hormone (hGH). By affinity column chromatography a complete separation of the hPRL and hGH binding units was achieved. It was thus shown that in choroid plexus the binding sites for GH and PRL occur as discrete entities. PMID- 1407378 TI - Abolition of prolactin surge induced by ovarian steroid hormones in the lactating rat. AB - There are data indicating that stress-induced prolactin (PRL) release is blunted in the lactating rat like the release of other stress-associated hormones. In this experiment, the PRL release evoked by administration of estrogen, which is another principal stimulus for PRL release, was examined in ovariectomized lactating rats 8-15 days after delivery. Estradiol benzoate (EB, 20 micrograms) injections into ovariectomized nonlactating rats induced a PRL surge starting between 13:00 and 15:00 h with a peak at 17:00 h 2 days after the treatment, whereas the EB-induced PRL surge was absent in ovariectomized lactating rats separated from their pups at 09:00 h on the day or in mothers without separation from their pups. Injection of either thyrotropin-releasing hormone (TRH; 10 micrograms/kg) or pimozide (0.5 mg/kg) elevated serum PRL concentrations similarly in lactating and nonlactating rats when examined just before the beginning of the expected estrogen-induced PRL surge. Thus, the main cause for the reduced PRL response to estrogen in lactating rats seems not to be in the pituitary gland but in the brain. Progesterone, which is known to induce a PRL surge in ovariectomized estrogen-primed rats by acting on the mediobasal hypothalamus, also failed to evoke a PRL surge in lactating rats. Recovery from the inhibitory influence of suckling on PRL response to EB followed a time course similar to that observed in response to immobilization stress or to morphine injection; estrogen-induced PRL surge started to recover at 6 days and was almost fully recovered 8 days after weaning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407379 TI - Time-dependent changes in beta-endorphin-stimulated prolactin release during pregnancy. AB - Endogenous opioid peptides (EOPs) stimulate prolactin (PRL) release in various physiological conditions in the rat. Moreover, EOPs are essential in initiating and maintaining the nocturnal PRL surges that occur over the first half of gestation in the rat. The purpose of this study was to investigate the potential role of the opioid beta-endorphin (beta-End) in mediating the nocturnal PRL surges. Day 8 pregnant rats received an infusion of 2.5, 10, 25 or 100 ng/microliters/min beta-End intracerebroventricularly (i.c.v.) for 15 min at 12.00 h, an intersurge period. PRL increased in a dose-dependent manner and from this, the largest dose was used in subsequent experiments to ensure maximal opioid receptor stimulation. The next experiment defined the temporal sensitivity of the neuroendocrine system regulating PRL surges to exogenous beta-End. Day 8 pregnant rats showed dramatic PRL responses to beta-End when given at midnight (presurge) or 12.00 h (intersurge), but greatly attenuated responses at 02.00 h (early surge) and 04.00 h (late surge). Animals treated at 06.00 h (postsurge) showed recovered responsiveness to beta-End. To determine what may account for the significantly lower PRL increases to beta-End during the surge, day 8 pregnant rats received 100 mg/microliters/min beta-End i.c.v. for 15 min at 10.00 h, and then again at 12.00 h. All animals showed PRL increases greater than 1,140 ng/ml at 10.00 h, but the subsequent response to beta-End at 12.00 h was reduced by 70%. In another experiment, beta-End was infused at midnight and the animals were monitored for a subsequent endogenous nocturnal PRL surge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407380 TI - Central oxytocin mediates inhibition of sodium appetite by naloxone in hypovolemic rats. AB - Pituitary oxytocin (OT) secretion is inversely related to saline consumption in several experimental models of sodium appetite in rats. Because systemic OT administration does not inhibit sodium appetite, release of OT as a neurotransmitter within the brain, coincident with its secretion from the pituitary, may be related to inhibition of sodium ingestion. The present studies evaluated this possibility by increasing brain OT concentrations both exogenously and endogenously in rats with hypovolemia produced by subcutaneous administration of polyethylene glycol (PEG) solution. Intracerebroventricular (i.c.v.) administration of OT completely abolished intake of 0.5 M NaCl in PEG-treated hypovolemic rats, but did not significantly affect PEG-stimulated water intakes. Endogenous OT secretion was stimulated by systemic treatment with naloxone, which has been shown to increase peripheral and central OT levels. In both one-bottle (0.5 M NaCl) and two-bottle (water and 0.5 M NaCl) drinking tests, intraperitoneal naloxone completely abolished sodium appetite in association with markedly increased pituitary secretion of OT. This inhibition of sodium appetite could be prevented by i.c.v. pretreatment with a specific OT-receptor antagonist, although the antagonist by itself did not affect PEG-stimulated sodium intake. These findings therefore support previous reports which have found that sodium appetite in rats is inhibited by treatments that elicit pituitary release of OT, and provide more direct evidence that brain OT is causally involved in the inhibition of sodium appetite stimulated by such treatments in rats. PMID- 1407381 TI - Exogenous androgen does not alter hypothalamic proopiomelanocortin gene transcript levels in the sexually immature male rat. AB - To investigate possible mechanisms whereby the augmentation of hypothalamic proopiomelanocortin (POMC) messenger ribonucleic acid (mRNA) levels occurs with pubertal development, we employed the techniques of testosterone administration and in situ hybridization histochemistry in sexually immature male rats. Six animals from each of the following groups were studied: (1) untreated controls (CTRL); (2) empty capsule (SHAM); (3) testosterone capsule (TEST), and (4) untreated adults (ADLT). Capsules were implanted at 21 days of age. Groups 1-3 were sacrificed at 35 days of life; group 4 at 55 days. Ventral prostate and seminal vesicle weights were obtained to assess the biologic effect of testosterone. Hybridizations were performed on coronal brain slices through the region of the arcuate nucleus using a 35S-labeled oligonucleotide probe complementary to a 30-base sequence within POMC mRNA. Anatomically matched tissue sections (11 per animal, from the retrochiasmatic region rostrally to the premammillary nucleus caudally) were exposed to x-ray film, followed by densitometric analysis. The mean serum testosterone concentration of the TEST group was significantly greater than that of the ADLT animals; values for the CTRL and SHAM rats were undetectable. The accessory sex organ weights of the ADLT animals were greater than those of the TEST rats; both values were greater than those of the CTRL and SHAM groups which were indistinguishable. Increased levels of hypothalamic POMC mRNA were observed in the male rat after pubertal development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407382 TI - Differential hypothalamic arginine vasopressin response to glucocorticoid receptor antagonism in lean and obese Zucker rats. AB - The obese Zucker rat (fa/fa) is an animal model for genetic obesity characterized by hyperphagia, hyperinsulinemia, and severe insulin resistance in peripheral tissues. Adrenal steroids seem to play an important role in the onset of fatty syndrome in these animals. There is strong evidence of abnormal regulation of the hypothalamic-pituitary-adrenal axis in obese Zucker rats. Considering the physiological function of arginine vasopressin (AVP) as an adrenocorticotropic hormone secretagogue, the present study was carried out to investigate the role of glucocorticoids in the control of hypothalamic AVP systems in lean and obese Zucker rats. In the first experiment, mifepristone (RU 38486), a glucocorticoid receptor antagonist, was administered for 4 days (10 mg/kg orally twice daily), and the expression of AVP mRNA in hypothalamic paraventricular and supraoptic nuclei was measured using in situ hybridization, and the concentrations of AVP in the pituitary gland and in the median eminence were quantified. Plasma corticosterone levels were also analyzed. Mifepristone treatment resulted in a threefold increase in plasma corticosterone levels in lean Zucker rats, but it did not change corticosterone secretion in obese animals. Mifepristone treatment decreased AVP mRNA levels in lean animals in the supraoptic nuclei, while in obese animals the AVP mRNA content was increased in the paraventricular nuclei. Mifepristone treatment significantly increased the concentration of AVP in the median eminence in lean rats and decreased it in obese animals. Mifepristone treatment did not change concentrations of AVP in the pituitary gland. In the second experiment, mifepristone was given for 4 days (10 mg/kg orally twice daily), and its effects on 24-hour food intake and plasma AVP concentrations were measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407383 TI - A method to assess the development of muscle power in preterms after term age. AB - The purpose of this paper is to report a detailed description of an instrument for evaluating the development of active and passive muscle power in preterms beyond term age. The instrument is constructed on a basis of age-specific items that assess these two components of muscle power and on the assumption that a persistent discrepancy between them serves to detect those preterms at most risk for disturbances in motor development. The application of the instrument is illustrated by reporting the individual trajectories of five case studies without any serious medical complications. It is concluded that if a marked discrepancy between active and passive power persists beyond the corrected age of 3 months, then this may be a sign of underlying pathology which will eventuate in abnormal postural outcomes and thereby disturbances in the control and coordination of movement. Having now provided a detailed description of how this instrument should be applied in postterm follow-up of preterm infants, we are currently examining its sensitivity and specificity on a much larger sample of similar subjects. PMID- 1407385 TI - The natural history of acute disseminated leukoencephalitis. A serial magnetic resonance imaging study. AB - The natural history of acute disseminated (leuko)encephalitis (ADE) in a 3-year old girl who did not receive steroid therapy is reported. Serial MR studies disclosed: 1) white matter lesions resolved spontaneously, though very slowly, 2) active disease persisted for around three months and coincided with the onset of new subcortical lesions. These subcortical lesions were associated with hyperactivity, suggesting a possible etiologic correlation. PMID- 1407384 TI - Battered child syndrome: cerebral ultrasound and CT findings after vigorous shaking. AB - Child abuse by whiplash-shaking can lead to severe cerebral damage, neurological defects and mental retardation. Cerebral damage has been found with and without external evidence of head injury. We report the sonographic findings in two children after traumatization due to repetitive vigorous whiplash shaking. Cerebral sonography revealed cerebral edema at admission or within 48 hours thereafter. Follow-up studies demonstrated development of marked brain atrophy in both cases. The sonographic findings were confirmed by cranial computerized tomography. Doppler sonography was used to monitor cerebral perfusion by measuring intracranial blood flow. The clinical history of the patients demonstrates that cerebral sonography in combination with Doppler sonography not only serves as a diagnostic tool but also allows adjustment of therapy to the actual clinical status of the patient. PMID- 1407386 TI - Acute encephalomyelitis: extending the neurological manifestations of acute rheumatic fever? AB - The clinical course of a five-year-old boy who developed meningeal irritation, encephalomyelitis, and optic neuritis four weeks after Streptococcus pyogenes pharyngitis is detailed. The patient responded to therapy with corticosteroids and recovered fully. Review of the literature reveals that a wide range of neurological disorders have been described in association with rheumatic fever. We suggest that disseminated encephalomyelitis in this child most probably was related to the streptococcal infection and that the spectrum of post-infectious neurological disorders associated with Streptococcus pyogenes may be broader than is currently appreciated. PMID- 1407387 TI - Kearns-Sayre syndrome with sideroblastic anemia: molecular investigations. AB - The progressive syndrome of Kearns-Sayre has been studied at the clinical, biochemical and genetic levels in a patient. Clinical arguments suggest an evolution from Pearson's disease to Kearns-Sayre syndrome. The respiratory chain activities were low, and Southern blot analysis, together with gene sequencing, showed a heteroplasmic deletion of 7767 base pairs in a significant proportion of the mitochondrial DNA in different tissues. Protein synthesis studies on lymphoblasts did not reveal any translation of the new reading frame created by the deletion, although the corresponding deleted mitochondrial DNA sequence is transcribed. PMID- 1407388 TI - Dominantly inherited hypoplasia of the vermis. AB - A mother and her two daughters with presumed dominantly inherited, non progressive, congenital cerebellar ataxia are reported. Magnetic resonance imaging revealed vermal hypoplasia in one case, and generalized hypoplasia of the cerebellum, predominating at the vermal level, in another case. These patients are identical to those previously published, except for a slowly progressive improvement of motor abilities observed during evolution. PMID- 1407389 TI - The epidemiology of progressive encephalopathies in childhood. I. Live birth prevalence in west Sweden. AB - Progressive encephalopathies in the west Swedish region were investigated in a population-based study. Cases were allocated to one of five main groups: 1) disorders covered by impairments in subcellular organelles, 2) disorders covered by deficiencies in the intermediate metabolism, 3) biochemically undefined neurometabolic disorders, 4) neuroimmunological disorders and 5) a symptom orientated miscellaneous group. Progressive encephalopathies were identified in 76 of 132,138 children born alive in the study area during the 16-year-period 1970-85. This gives a live birth prevalence of 0.58 per 1000. In Sweden the size of the group corresponds to that of neural tube defects and that of congenital hydrocephalus. However, a vast number of different disorders are represented. PMID- 1407390 TI - Cerebral occipital calcifications in celiac disease. AB - Bilateral occipital calcifications, occurring in celiac disease, are factors coming under a particular cerebral syndrome, which also includes epilepsy, migraine-like headache, visual troubles and mental deterioration. They seem to arise from hypofolatemia following gluten-induced enteropathy. PMID- 1407391 TI - Sudden loss of hearing and vestibular function, muscular weakness, and multiple white matter lesions in preschool children. AB - Sudden cochlear hearing loss, occurring successively or simultaneously in both ears, was observed in four unrelated preschool children. Vestibular testing could be carried out in three patients and showed complete bilateral loss of function. All patients had a mildly retarded motor development due to nonprogressive muscular weakness. On MR imaging all patients showed multiple periventricular and subcortical white matter lesions. These lesions were not clearly progressive in one patient examined repeatedly over 6 years. Virological, bacteriological, immunological, and metabolic examinations were normal in all patients. Muscle biopsy showed morphologically abnormal mitochondria in two and lipid storage in one patient. No indications have been found for a disturbed functioning of the muscle mitochondria. The identical pattern and course of the disease in these patients suggests a new nosological entity, the aetiology of which can only speculatively be attributed to a vascular process associated with a mitochondriopathy. PMID- 1407392 TI - Central action of 5-HT3 receptor ligands in the regulation of sleep-wakefulness and raphe neuronal activity in the rat. AB - Anxiolytic drugs, such as the benzodiazepines and the azapirones (ipsapirone, gepirone, buspirone), are well known to affect states of vigilance and to decrease the firing rate of serotoninergic neurones within the dorsal raphe nucleus in rats. In order to examine whether the newly developed 5-HT3 antagonists with potential anxiolytic properties act through similar mechanisms, the effects of several of such antagonists: MDL 72222, ICS 205-930, ondansetron and/or zacopride on both sleep-wakefulness and the discharge of serotoninergic neurones within the dorsal raphe nucleus were investigated in rats. When tested in a wide range of doses (0.05-10 mg/kg, i.p.), none of these drugs significantly affected the states of vigilance, except ondansetron, at 0.1 mg/kg, which increased paradoxical sleep for the first 2 hr after administration and MDL 72222, at 10 mg/kg, which reduced both paradoxical and slow wave sleep and increased wakefulness for the same initial period after treatment. In vivo, in chloral hydrate anaesthetized rats, as well as in vitro, in slices of brain stem, none of the 5-HT3 antagonists tested affected the firing rate of serotoninergic neurones. Similarly, no change in the electrical activity of serotoninergic neurones could be evoked in vitro by superfusion of the tissue with the 5-HT3 agonists, phenylbiguanide (10 microM) and 2-methyl-5-HT (1 microM). At a larger concentration (10 microM), the latter compound reduced the neuronal discharge probably through the stimulation of somatodendritic 5-HT1A autoreceptors since this effect, as that of ipsapirone, could be prevented by 10 microM l propranolol. Comparison of these data with those obtained with benzodiazepines and 5-HT1A agonists of the azapirone series, supports the concept that different mechanisms are responsible for the anxiolytic-like properties of 5-HT3 agonists, compared to those of other anxiolytic drugs. PMID- 1407393 TI - A post-synaptic depressant modulatory action of 5-hydroxytryptamine on excitatory amino acid responses in rat entorhinal cortex in vitro. AB - The depressant action of 5-hydroxytryptamine (5-HT) in slices of entorhinal cortex of the rat has been examined. When single intracellular recordings of pyramidal cells in layers II/III of entorhinal cortex of the rat were made and drugs applied by iontophoresis, 5-HT evoked virtually no changes in passive membrane properties of the majority of cells studied. When short regular pulses of glutamate were applied to the neurones and 5-HT was ejected in addition, the depolarisations caused by glutamate were considerably reduced in amplitude. This attenuation persisted in medium containing cadmium chloride (200 microM) to block synaptic transmission. The magnitude of the response to 5-HT was dependent on the ejection current and this effect could not be mimicked by increasing ejections of Na+ or H+ ions. 5-Hydroxytryptamine had no apparent action on neuronal responses to iontophoretically ejected gamma-amino butyric acid (GABA). In later studies, the action of 5-HT was examined on epileptiform discharges, evoked in the presence of the GABA antagonist, bicuculline, in the same group of cells. Droplet application of 5-HT into the recording chamber, or perfusion of 10 microM 5-HT regularly attenuated the length of epileptiform bursts but, at this concentration, had no discernible effect on the resting membrane potential or membrane input resistance. The effect of 5-HT on the release of glutamate from slices of entorhinal cortex has also been examined using a fluorometric enzyme assay. Concentrations of 5-HT as large as 30 microM had no effect on the release of endogenous glutamate in these experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407394 TI - The putative 5-HT1A antagonist BMY 7378 blocks 8-OH-DPAT-induced changes in local cerebral glucose utilization in the conscious rat. AB - It has previously been shown that the 5-HT1A agonist, 8-OH-DPAT, caused discrete changes in cerebral glucose utilization in the rat, as assessed by quantitative 2 deoxyglucose autoradiography. Here, the effect of the putative 5-HT1A antagonist, BMY 7378, on regional cerebral glucose utilization was examined, when injected alone and in rats treated with 8-OH-DPAT. In control rats, BMY 7378 (5 mg/kg, s.c.) markedly increased glucose utilization in the lateral habenular nucleus and moderately reduced glucose utilization in the hippocampal formation. Pretreatment with BMY 7378 (5 mg/kg) significantly attenuated the reductions in glucose utilization in the hippocampus, entorhinal, piriform and cingulate cortex, induced by 8-OH-DPAT (0.25 mg/kg). The 8-OH-DPAT-induced increase in glucose utilization in the copula pyramis, that is putatively associated with the appearance of the 5-HT behavioural syndrome, was also blocked by BMY 7378, as was the behavioural syndrome. In summary, BMY 7378 produced few of the discrete changes in cerebral glucose utilization that are seen with 8-OH-DPAT. However, many of the changes induced by 8-OH-DPAT were reversed by BMY 7378. These data are consistent with the hypothesis that the effects of 8-OH-DPAT on regional cerebral glucose utilization are mediated by 5-HT1A receptors. PMID- 1407395 TI - Attenuation of defensive analgesia in male mice by 5-HT3 receptor antagonists, ICS 205-930, MDL 72222, MDL 73147EF and MDL 72699. AB - Recent studies have shown that non-opioid defensive analgesia in male mice is potently inhibited by the 5-HT3 receptor antagonist, ondansetron. The present series of experiments was conducted to further explore the involvement of 5-HT3 receptor mechanisms in this particular form of adaptive inhibition of pain. The drug ICS 205-930 significantly attenuated the reaction at 1.25-2.5 micrograms/kg, with smaller and larger doses being ineffective. Both MDL 72222 and MDL 73147EF produced flat dose-response curves, with significant inhibition of defensive analgesia at minimum effective doses of less than or equal to 10 and 300 micrograms/kg, respectively. Although MDL 72699, the quaternary salt of MDL 72222, also inhibited the reaction, this effect was seen at comparatively large doses (0.5-1.0 mg/kg) only. None of the compounds tested had significant intrinsic effects of tail-flick latencies, over the dose ranges tested. These findings indicate that 5-HT3 receptor mechanisms may have an important modulatory role in certain forms of "stress" analgesia. Data are discussed in relation to the consistent profile of partial inhibition produced by 5-HT3 receptor antagonists in this model. PMID- 1407396 TI - 5-HT3 receptors in NG108-15 neuroblastoma x glioma cells: effect of the novel agonist 1-(m-chlorophenyl)-biguanide. AB - The effect of the novel agonist, 1-(m-chlorophenyl)-biguanide (mCPBG) was examined on 5-HT3 receptors in NG108-15 mouse neuroblastoma x rat glioma hybrid cells, using whole-cell voltage-clamp and radioligand binding on intact cells. Electrophysiological studies showed that mCPBG is a partial agonist, with an EC50 of 3.1 microM. Displacement of the selective 5-HT3 receptor antagonist [3H]GR65630 by mCPBG revealed a Ki of 14.2 nM. The study suggests that mCPBG may have a high affinity for desensitized 5-HT3 receptors and also revealed some differences between 5-HT3 receptors in NG108-15 and N1E-115 cells. PMID- 1407397 TI - N-methyl-D-aspartate receptors in the retina: 3-[(+/-)-2-carboxypiperazin- 4-yl] propyl-1-phosphonic acid (CPP) binding studies. AB - 3-[(RS)-2-Carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) has been known for some years as one of the most selective antagonists at the N-methyl-D aspartate (NMDA) receptor in the brain. The characteristics of the binding of [3H]CPP to chick retinal membranes were studied from the biochemical and pharmacological point of view. Magnesium induced a dose-dependent increase in the binding of [3H]CPP (EC50 = 4 microM). In the absence of this ion, a single population of receptors was found (KB = 431 nM; Bmax = 9.5 pmol/mg protein), which was not modified by the addition of 1 mM MgCl2. An additional, high affinity site (KB = 59 nM; Bmax = 2.2 pmol/mg protein) became evident in the latter condition. Saturation curves of the binding of [3H]CPP, using 1 mM AMPA [(RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate] or L-aspartate, as displacers in the presence of Mg2+, showed a KB = 200 and 395 nM, respectively. The relative potency of some analogues of excitatory amino acids, for displacing bound CPP in the absence of Mg2+, was AMPA = APH greater than L-glutamate = CPP; Mg2+ significantly increased the potency of AMPA, APH and L-glutamate. These results showed that CPP bound to high affinity (Mg(2+)-dependent) and low affinity sites and that AMPA and L-aspartate compete with this compound only at the low affinity sites. These findings suggest that either the binding of CPP in the retina shows different properties from those described in the brain or alternatively, that AMPA is not as specific for the quisqualate receptor in this organ. PMID- 1407398 TI - Antidiuretic effects of purinoceptor agonists injected into the hypothalamic paraventricular nucleus of water-loaded, ethanol-anesthetized rats. AB - The effects of injection of various purinoceptor agonists into the hypothalamic paraventricular nucleus in water-loaded and ethanol-anesthetized rats were investigated. Adenosine triphosphate (ATP), beta,gamma-methyleneadenosine 5' triphosphate (AMP-PCP) and beta,gamma-imidoadenosine 5'-triphosphate (AMP-PNP) potently decreased the outflow of urine in a time- and dose-dependent manner. The ED50 values were approx 70 and 37 nmol for ATP and AMP-PCP, respectively. Adenosine diphosphate (ADP), AMP and adenosine reduced the outflow of urine much less than ATP. Adenosine triphosphate induced concomitant increases in the osmotic pressure of the urine and in the level of arginine-vasopressin (AVP) in plasma. The antidiuretic effect of ATP was blocked by prior injection of quinidine (a P2-purinoceptor antagonist) into the paraventricular nucleus, but not by the prior injection of theophylline (a P1-purinoceptor antagonist). The effect of ATP was also blocked by intravenous injection of an AVP(V1V2)-receptor antagonist, d(CH2)5-D-Tyr(Et)VAVP. The results suggest that ATP injected into the paraventricular nucleus may stimulate a purinoceptor, releasing AVP and inducing the antidiuretic effect through renal AVP(V2) receptors. PMID- 1407399 TI - Oxytocin modulates behavioural adaptation to repeated treatment with cocaine in rats. AB - Behavioural adaptation to and the effects of the neurohypophyseal peptide, oxytocin, on repeated treatment with cocaine were investigated in rats. The content of immunoreactive oxytocin in the plasma, hypothalamus and different limbic structures in the brain were also studied after treatment with cocaine, identical to that used in the behavioural experiment. Repeated administration of cocaine (7.5 mg/kg, s.c.) produced a behavioural tolerance to the stereotyped sniffing-inducing effect of the challenge doses (1.875, 3.75 and 7.5 mg/kg, s.c.) of cocaine on the fifth day, which was demonstrated by parallel shifting of the dose-response and time-effect curves of the test doses of cocaine. The development of tolerance was inhibited by pretreatment with oxytocin (0.05 micrograms, (s.c.), administered before each daily injection of cocaine. A smaller dose of oxytocin (0.005 micrograms, s.c.) had no effect in this model. A decreased amount of immunoreactive oxytocin was detected in the plasma, in the hypothalamus and in the hippocampus, after repeated treatment with cocaine. Replacement of oxytocin by local injection (100 pg) into the ventral hippocampus, before each daily administration of cocaine, prevented the development of tolerance to cocaine. These results suggest that endogenous oxytocin, localized in limbic-forebrain areas, may have an important regulatory role in the development of behavioural changes induced by the repeated administration of cocaine. PMID- 1407400 TI - Phylogenetic tree analysis of G protein-coupled 5-HT receptors: implications for receptor nomenclature. AB - The nomenclature system used to characterize 5-hydroxytryptamine receptor subtypes remains controversial. To date, the majority of nomenclature systems have been on the differential pharmacological properties of the receptors. However, the availability of molecular biological data allows for a nomenclature system based on the structural properties of the receptors. The evolutionary relationships between the known G protein-coupled 5-HT receptor subtypes were determined by a phylogenetic tree analysis. The data indicate that 2 major classes of G protein-coupled 5-HT receptors have evolved. Each of the 2 branches differentiate into additional 5-HT receptor subtypes. The most recent branching of 5-HT receptor subtypes occurs at the level of individual species. These data also indicate that the degree of structural similarity (e.g. 93% identify between human and rat 5-HT1B receptors) does not necessarily correlate with pharmacological similarity. Phylogenetic tree analysis allows for a nomenclature framework that can be easily expanded to incorporate additional 5-HT receptor subtypes that have yet to be identified. PMID- 1407401 TI - (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane(DOI) and alpha-methyl-5-HT: 5 HT2 receptor agonistic action on phosphatidylinositol metabolism in the rat fronto-cingulate and entorhinal cortex. AB - In the present study, the effects of 5-HT and two 5-HT1c/5-HT2 receptor agonists, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and alpha-methyl serotonin (alpha-Me-5-HT) on phosphoinositide hydrolysis were compared, to determine whether DOI and alpha-Me-5-HT were full agonists. Consistent with the results obtained from previous studies, both (+/-)-DOI and alpha-Me-5-HT stimulated turnover of phosphoinositide in a concentration-dependent manner. However, the response obtained with these 5-HT1c/5-HT2 receptor agonists was only 30-40% of that of 5-HT. The stimulation of hydrolysis of phosphoinositide, produced by both 5-HT2 receptor agonists, was potently antagonized by ritanserin (a 5-HT1c/5-HT2 receptor antagonist) and alpha-phenyl-1-(2-phenylethyl)-4 piperine methanol [(+)-MDL 11,939, a 5-HT2 receptor antagonist] but not by granisetron (BRL a 5-HT3 receptor antagonist), suggesting that the action of DOI and alpha-Me-5-HT was primarily mediated by 5-HT2 receptors. When the effect of increasing the concentration of 5-HT on turnover of phosphoinositide was measured in the presence of a 1 microM concentration of the 5-HT3 receptor antagonist granisetron, the response obtained was similar to the response produced by the 5 HT2 receptor agonists, DOI and alpha-Me-5-HT. These results confirm the previous finding that 5-HT stimulates hydrolysis of phosphoinositide by interacting with 5 HT1c/5-HT2 and 5-HT3 receptors. Moreover, they suggest that DOI and alpha-Me-5-HT are full agonists at the 5-HT2 receptor, coupled to hydrolysis of phosphoinositide in the cortex of the rat. PMID- 1407402 TI - 5-HT1-like receptor agonists enhance wakefulness. AB - The effects of four 5-HT1-like receptor agonists (8-OH-DPAT, RU 24969, BEA 1654 and 5-carboxamidotryptamine) and some putative 5-HT1-like receptor antagonists on vigilance were examined in an attempt to clarify the role of 5-HT1-like receptors in the sleep-waking pattern of rats. Both 8-OH-DPAT (0.5-2.0 mg/kg, s.c.) and RU 24969 (0.5-2.0 mg/kg, s.c.) increased wakefulness and the latencies of slow wave and rapid eye movement (REM) sleep. The slow wave and REM sleep were correspondingly decreased or completely abolished. The two other 5-HT1-like receptor agonists had either a slight (BEA 1654, 1.0-5.0 mg/kg, s.c.) or no (5 carboxamidotryptamine, 0.5-2.0 mg/kg, s.c.) effect on sleep pattern. The arousal effect of 8-OH-DPAT was further potentiated in rats pretreated with reserpine (2.5 mg/kg, i.p.; 18 hr before 8-OH-DPAT). The non-selective 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (2.0 mg/kg, i.p.) and the beta-adrenoceptor antagonist propranolol (16.0 mg/kg, s.c.), which is a putative antagonist at 5 HT1A and 5-HT1B receptor subtypes, significantly potentiated the arousal effect of RU 24969. The putative 5-HT1A and 5-HT1B receptor antagonist, cyanopinolol (4.0 mg/kg, s.c.), mixed 5-HT1A receptor agonist/antagonist MDL 72832 (1.0 mg/kg, s.c.) and the alpha 1-adrenoceptor antagonist prazosin (2.0 mg/kg) did not affect the vigilance, altered by RU 24969. These results suggest that the arousal effect of 5-HT1-like receptor agonists is probably not mediated by any of the subtypes of 5-HT1-like receptors or by an activation of a noradrenergic system. PMID- 1407403 TI - Stimulatory and inhibitory effects of serotonergic hallucinogens on spinal mono- and polysynaptic reflex pathways in the rat. AB - The effects of two 5-HT-related hallucinogens on rat spinal mono- and polysynaptic reflex pathways in the rat were investigated. 5-Methoxy-N,N dimethyltryptamine (5-MeODMT, 1 and 100 micrograms/kg, i.v.), an indolealkylamine agent, produced a dose-dependent decrease in the monosynaptic reflex, whereas 1 (2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1-100 micrograms/kg), a phenylalkylamine agent, produced a dose-dependent increase in the monosynaptic reflex. Both agents increased the polysynaptic reflex. The 5-HT2 receptor antagonists ketanserin (100 micrograms/kg) and ritanserin (100 micrograms/kg) blocked the effects of DOI on the monosynaptic reflex but only partially blocked the 5-MeODMT-induced effect on the monosynaptic reflex. These antagonists inhibited the change in polysynaptic reflex, induced by DOI but not by 5-MeODMT. Neither propranolol (1 mg/kg) nor 3-tropanyl-3,5-dichlorobenzoate (MDL 72222, 1 mg/kg) antagonized the effect of either agent. 5-Methoxy-N,N-dimethyltryptamine and DOI increased the excitability of motoneurons and this effect was inhibited by ketanserin. These results indicate that the two types of hallucinogens possess both common and distinct characteristics, with regard to their action on the spinal reflex: (1) both increase the activity of motoneurons through 5-HT2 receptors but (2) only 5-MeODMT has an inhibitory action on the pathway of the monosynaptic reflex. PMID- 1407404 TI - Blockade of dopamine autoreceptors by haloperidol and the apparent dynamics of potassium-stimulated endogenous release of dopamine from and reuptake into striatal suspensions in the rat. AB - A study was made to determine what effects the blockade of dopamine (DA) autoreceptors has on the dynamics of depolarization-stimulated release of DA from suspensions of the striatum. A rotating disk electrode voltammetric technique and a first order kinetic model were used to measure and quantify time-resolved depolarization-induced release of DA from and reuptake into the same striatal suspension. Multiphasic dose-response relationships between the magnitudes, rates and apparent rate constants of release of DA and the concentration of the autoreceptor antagonist, haloperidol, were observed. At small concentrations of haloperidol, less than or equal to 0.1 microM, the magnitude of release of DA and apparent release rate constants were increased, however, the duration of release, the initial rate of release and the rate constants of reuptake of DA were unaffected. At larger concentrations of haloperidol, greater than 1.0 microM, release of DA was prolonged and reuptake was decreased. The rate constants for release of DA correlated with the magnitude of release of DA at all of the concentrations of haloperidol studied. The concentrations of haloperidol in tissue were estimated and then correlated with functionally significant systemic doses of haloperidol by direct comparison to published data, relating total concentrations of haloperidol in tissue with systemic doses and their behavioral effects. At these doses, haloperidol was found to increase the release rate constant and magnitude of release of DA, without altering the duration of release or the timing of reuptake. Thus, at presumed functionally significant doses, autoreceptor antagonism resulted in a modulation of the amplitude of release of DA only. PMID- 1407405 TI - The effect of antidepressant drugs on the locomotor hyperactivity induced by MK 801, a non-competitive NMDA receptor antagonist. AB - It was found earlier that imipramine, amitriptyline and citalopram enhanced the locomotor hyperactivity induced by MK-801, a non-competitive NMDA receptor antagonist, in rats. Now, three other antidepressants: (+)-oxaprotiline, an inhibitor of the uptake of noradrenaline, (-)-oxaprotiline, an enantiomer devoid of any effect on the uptake of noradrenaline and fluoxetine, an inhibitor of the uptake of 5-hydroxytryptamine, have been examined in male Wistar rats. All those antidepressants, given in a single dose, increased the MK-801-induced locomotor hyperactivity. That increase was completely antagonized by haloperidol and partly by SCH 23390 and (+/-)-sulpiride; prazosin was inactive. Repeated administration of antidepressants produced a similar but more potent (than acute one) enhancement of the action of MK-801. Also, in that case haloperidol and SCH 23390 produced the strongest antagonistic effect; (+/-)-sulpiride and prazosin had a distinctly less potent action. Another effect of MK-801, anticonvulsant activity (electroshock-induced convulsions), was not increased by the antidepressants studied. These results indicate that antidepressants with a different pharmacological profile, increased the MK-801-induced locomotor hyperactivity, this effect being probably indirectly mediated, at least in part, by a dopamine mechanism. PMID- 1407406 TI - Behavioral and neurochemical effects of continuous infusion of cocaine in rats. AB - The ability of continuous intravenous infusion of cocaine (60 mg/kg per day for 11 or 12 days; by osmotic minipump) to alter responses to acute injection of cocaine (20 mg/kg, i.p.; given 24 hr after termination of the infusion by minipump) was tested in conscious, tethered Sprague-Dawley rats. Extracellular levels of cocaine, dopamine and metabolites of dopamine in the striatum were determined by in vivo microdialysis. Locomotor activity and stereotyped behavior were evaluated simultaneously during dialysis sampling. Prior infusion of cocaine blunted the ability of acute challenge with cocaine to increase the efflux of dopamine in the striatum, locomotor activity and stereotypy. Increases in extracellular levels of homovanillic acid in the striatum were significantly greater in cocaine-infused rats than vehicle-infused controls, both prior to and after acute injections of cocaine. However, no differences between these two groups were observed in levels of cocaine in the striatum after acute challenge. Extracellular levels of dopamine in the striatum correlated significantly (P less than 0.05) with stereotypy in both groups but with locomotor activity only in cocaine-infused rats. The results indicate that behavioral tolerance occurred after continuous intravenous infusions of cocaine, that this was correlated with neurochemical tolerance to acute cocaine challenge and that alterations in the metabolism of cocaine did not account for the observed behavioral responses. PMID- 1407407 TI - The effect of 3-amino-1,2,4-triazole on voluntary ethanol consumption: evidence for brain catalase involvement in the mechanism of action. AB - The effects of the catalase inhibitor, 3-amino-1,2,4-triazole (AT), on maintenance of voluntary consumption of ethanol was tested in male Long-Evans rats. AT produced a dose-dependent reduction in ethanol intake but did not affect total fluid consumption. AT also produced a dose-dependent inhibition of brain catalase lasting throughout the drinking period. These results suggest a role for brain catalase in determining the level of ethanol intake in rats. PMID- 1407408 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1407409 TI - Transfer of [3H]leucine across the blood-brain barrier at high blood-side oxytocin concentrations in normal and morphine-dependent rats. AB - The effects of circulating oxytocin on permeability of the blood-brain barrier (BBB) to L-[3H]leucine were studied in anaesthetized rats using the intracarotid, single pass, bolus injection technique. After bolus intracarotid oxytocin injection (10(-9) M), there were no differences in [3H]leucine uptake, compared with controls, in any of eight brain regions with a 'tight' BBB (olfactory bulb, frontal cortex, visual cortex, corpus striatum, hippocampus, thalamus, hypothalamus and colliculi) or in BBB-free, 'leaky' structures (pineal gland, choroid plexus, neuro-intermediate pituitary, anterior pituitary). [3H]leucine uptake by the 'leaky' structures was 2.4x and 2.6x uptake by 'tight' regions in the oxytocin and control groups respectively. In morphine-dependent rats, naloxone increased oxytocin secretion 28-fold within 5 min, but did not affect [3H]leucine uptake for any BBB-protected brain region or BBB-free 'leaky' structure. Accumulation of [3H]leucine was 8.3x and 7.0x greater in the 'leaky' structures than in the 'tight' regions in the naloxone and control groups respectively; [14C]inulin accumulation by each 'tight' region (measured simultaneously with [3H]leucine to determine the vascular space) was not affected by naloxone. It is concluded that even very high blood plasma concentrations of oxytocin do not affect BBB permeability for leucine. It is unlikely that altered BBB permeability, at least for amino acids, contributes to CNS changes during naloxone-provoked morphine withdrawal. PMID- 1407410 TI - CSF enkephalins in diabetic neuropathy. AB - CSF methionine and leucine enkephalins were measured by high performance liquid chromatography and radioimmunoassay in diabetic patients with painful neuropathy (n = 22) and painless neuropathy (n = 5), and non-diabetic subjects with low back pain (n = 11). Wide variations in CSF enkephalin levels were found and they were often below the limit of detection (less than 0.1 pmol/l) in the diabetic and non diabetic groups. The origin of CSF enkephalins is unknown and CSF levels may not reflect tissue concentrations. In conclusion, CSF enkephalin levels are difficult to interpret and do not provide useful information on the function of enkephalinergic pathways. PMID- 1407411 TI - Prolactin response to anesthetic stress and beta-endorphin is altered in female rats treated neonatally with monosodium glutamate. AB - MSG (4 mg/g, sc) or saline was administered to neonatal female rats on days 1, 3, 5, 7 and 9. Study 1) Prl levels were assessed at 30, 60 and 75 days after birth to monitor possible development of hyperprolactinemia. No hyperprolactinemia was observed at any time studied. Study 2) MSG and control rats were administered pentobarbital anesthesia at 2 months of age. At 20, 60 and 90 min following anesthesia, plasma was collected for assay of Prl. 20 min prior to the 90 min bleeding, BE (5 micrograms/5 ul) was stereotaxically administered, into the third ventricle. MSG-treated rats had an attenuated Prl response to the stress of anesthesia (bleeding 1). Prl levels in control and MSG-treated rats were similar at 60 min post-anesthesia (bleeding 2) which represented a return of Prl levels to baseline after stress-induced elevation of Prl. Control and MSG-treated rats exhibited an increase in plasma Prl following intracerebroventricular BE; however, the amplitude of this response was markedly attenuated in the MSG treated animals (bleeding 3). Thus, an observed loss of TH-positive neurons in the arcuate nucleus of the hypothalamus following MSG treatment and the attenuated response of Prl to anesthesia-stress and BE administration suggests that Prl secretion in response to these agents is operative through inhibition of the TIDA system. Furthermore, these studies show that the Prl response to these agents (anesthetic and BE) is intact but sub-operational in MSG-treated rats. PMID- 1407413 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1407412 TI - Cerebrospinal fluid endothelin-1 in Alzheimer's disease and senile dementia of Alzheimer type. AB - We have measured the endothelin-1 concentrations in the cerebrospinal fluid samples from 5 patients with Alzheimer's disease (AD), 6 patients with senile dementia of Alzheimer type (SDAT) and 7 patients with other diseases without dementia (disease control: DC). The cerebrospinal fluid endothelin-1 level was significantly lower in AD than in DC. No correlation was observed between cerebrospinal fluid endothelin-1 concentration and any other factors such as age, duration from onset, systolic blood pressure, cerebrospinal fluid protein level or plasma endothelin-1 concentration in AD or SDAT. These results suggest a possible alteration of the endothelin-1 system in the central nervous system in Alzheimer's disease. PMID- 1407414 TI - Effects of cocaine on the contents of neurohypophyseal hormones in the plasma and in different brain structures in rats. AB - The effects of acute and chronic cocaine treatments on the levels of the neurohypophyseal hormones oxytocin (OXT) and vasopressin (AVP) in the plasma and in different brain structures in rats were measured by radioimmunoassay (RIA). Acute cocaine treatment had no effect on the level of OXT in the plasma or in the amygdala, but increased OXT contents were measured in the hypothalamus and in the hippocampus. The OXT levels in the basal forebrain structures (including the septum and the nucleus accumbens) were decreased by a single dose of cocaine. The acute injection of cocaine increased the level of AVP in the plasma, and decreased contents of OXT were measured in the amygdala and in the basal forebrain. Repeated treatment with cocaine decreased the level of OXT in the plasma, hypothalamus and hippocampus. The AVP contents were decreased in all of the brain structures investigated, but no change was caused in the plasma level of AVP by repeated injections of cocaine. These results demonstrate complex, region-specific interactions between cocaine and the neurohypophyseal hormones in the brain and in the periphery underlying the alteration in behavioral and autonomic functions caused by acute and chronic cocaine exposure. PMID- 1407415 TI - Disturbance of spatiotemporal footfall contact patterns in the rat by TRH analogue CG3703. AB - Administration of TRH or its analogues to a rat changes the dynamics of locomotion resulting in shorter stance times and causes postural disturbances, including hunched back and pelvic girdle elevation. Locomotor disturbance, induced by a variety of methods, results in changes to the footfall patterns during the stance phase of locomotion. The present work investigated whether these postural and locomotor dynamic disturbances in the CG3703 treated rat were associated with changes to the pattern of paw/floor contact during locomotion. It was found that in treated animals the area of hindpaw contact increased while that of the forepaw decreased from control values. The pattern of contact changed, with hindpaw stance being shifted towards more distal elements while in the forepaw a reduction in the deployment of proximal elements without any compensating increase in distal contact was seen. These results are discussed in the context of the effects of TRH analogues on sensory and motor processing in the CNS. PMID- 1407416 TI - Interleukin-6 and corticotrophin-releasing hormone mRNA are modulated during differentiation of human neuroblastoma cells. AB - Two cell clones [BE(2)-C and BE(2)-M17] derived from the human neuroblastoma cell line SK-N-BE(2) express corticotrophin-releasing hormone as well as interleukin-6 mRNA. Both genes are overexpressed, although with a different time course, following exposure to 5 microM retinoic acid, in parallel to the induction of neuroblastic differentiation. On the contrary, we are unable to detect interleukin-1 beta mRNA in these cell lines. Both cytokines are known to increase hypothalamic CRH mRNA. The production of cytokines and neuropeptides by neuroblastoma cells indicate a complex dialogue between tumour cells and anti tumour immunity. PMID- 1407417 TI - Effects of intracerebroventricular administration of calcitonin gene-related peptide on passive avoidance behaviour in rats. AB - The effects of different doses of calcitonin gene-related peptide (CGRP) on passive avoidance behaviour were studied in male rats following its intracerebroventricular (i.c.v.) administration. Treatment with doses of 200 ng, 300 ng, 500 ng or 1 microgram was performed prior to learning, immediately and 6 h after the learning session and 30 min before the 24 h retention test. CGRP enhanced the avoidance latency in a dose-dependent manner at each time studied, with the exception of 6 h after the learning session. It is concluded that CGRP might be able to lengthen the passive avoidance latency by facilitating learning and memory formation. PMID- 1407418 TI - Comparison of the effects of neurotensin and vasopressin on the adrenal cortex of dexamethasone-suppressed rats. AB - Neurotensin (NT) and vasopressin (AVP) share some similarities as far as their actions on the adrenal weight and secretion are concerned. The present study aimed to compare the in vivo chronic effect of these two peptides on the adrenal cortex of dexamethasone (Dx)-treated rats. NT or AVP were ip. infused at a rate of 2 micrograms/rat/d for 7 d. In the animals concomitantly treated with 15 micrograms Dx/100 g/d for 7 d, both NT and AVP partially prevented adrenal atrophy. AVP enhanced plasma aldosterone concentration (PAC), but not that of corticosterone (PBC). On the other hand, NT did not affect either PAC or PBC. In rats treated with 35 micrograms Dx/100 g/d for 14 d, neither NT nor AVP administered for the last 7 d exerted any effect on the adrenal weight. However, also under these conditions of profound adrenal atrophy AVP was still able to notably raise PAC, while NT was ineffective. Our findings indicate that the mechanism underlying the aldosterone secretagogue action of AVP does not require, unlike that of NT, the presence of ACTH. Moreover, in light of many recent literature data they could suggest the possibility that in vivo NT acts on the rat adrenal cortex via AVP. PMID- 1407419 TI - Comparison of the clinical presentation of symptomatic arteriovenous malformations (angiographically visualized) and occult vascular malformations. AB - The authors compared the clinical presentations of angiographically apparent arteriovenous malformations (AVMs) and angiographically occult vascular malformations (AOVMs) of the brain in 188 consecutive patients treated when computed tomography and magnetic resonance were available. There were 133 patients (70.7%) with AVMs and 55 patients (29.2%) with AOVMs. AOVMs tended to occur more frequently in male patients and in the posterior fossa and to present earlier clinically than AVMs, but differences were not significant. One distinctive feature was the greater size of AVMs, as compared with AOVMs. Presentation by hemorrhage occurred in 64.3% of the patients with AVMs and in 61.8% of those with AOVMs. Malformations of both types located in the posterior fossa presented with hemorrhage more frequently (84.2% of AVMs and 78.5% of AOVMs) than similar lesions lying above the tentorium (60.8% of AVMs and 56% of AOVMs). Bleeding was more severe in patients with AVMs than in those with AOVMs, as indicated by the higher mortality associated with hemorrhage (7.5 vs. 3.6% of the cases) and the more frequent and marked decrease in the level of consciousness observed at admission (34 vs. 16.2% of drowsy or comatose patients). Brain hematomas caused by AVMs were on average bigger than those caused by AOVMs (58.8 and 20% of large hematomas, respectively), and intraventricular and subarachnoid hemorrhages were also more common and profuse in patients with AVMs. However, AOVMs bled subsequently more times than AVMs (61.7 vs. 15.6%), before they were diagnosed and treated, leading to a higher nonoperative morbidity (16.3 vs. 13.6%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407420 TI - Involvement of the external carotid arteries in moyamoya disease: neuroradiological evaluation of 66 patients. AB - Arterial stenoses and/or occlusions in moyamoya disease are mainly localized intracranially, although some instances of stenotic lesions of the extracranial arteries have been reported in some autopsy cases. We have reviewed the angiograms of 66 patients with moyamoya disease to investigate whether stenotic lesions are present in the external carotid artery and its branches. We noticed that 13 patients had stenoses in the branches of the external carotid artery, although no occlusions were recognized. This result indicates that the arterial stenoses and/or occlusions are not confined to the intracranial arteries and that systemic factors contribute to the pathogenesis of moyamoya disease. This result also suggests that studies on specimens of the superficial temporal artery, which can be obtained easily at surgery, may reveal the molecular mechanism of intimal thickening. PMID- 1407421 TI - Surgical treatment of moyamoya disease in pediatric patients--comparison between the results of indirect and direct revascularization procedures. AB - Either encephaloduroarteriosynangiosis (EDAS) or superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis combined with encephalomyosynangiosis (EMS) has been performed on most of the children with moyamoya disease in our department. EDAS alone was done in the parietal region of 13 sides in 10 patients, and STA-MCA anastomosis with EMS in the parietal region was done on 7 sides in 6 patients. The surgical results of these two different procedures were then compared. Postoperative collateral formation was observed on external carotid angiograms, and the improvement of clinical symptoms was monitored for 1 year after the bypass procedure. STA-MCA anastomosis with EMS was found to be superior to EDAS in both the development of collateral circulation (P less than 0.05) and postoperative clinical improvement (P less than 0.01). EDAS can be done easily and safely on small children with moyamoya disease, but STA MCA anastomosis with EMS is considered to be more appropriate, whenever possible. PMID- 1407422 TI - Neurinomas presenting as spontaneous intratumoral hemorrhage. AB - Massive intratumoral or subarachnoid hemorrhage from neurinomas is very rare. The authors report on six patients, four men and two women, with neurinomas that presented as spontaneous intratumoral hemorrhage. The average age of the patients was 56.8 years (range, 31-74 years). Neurinomas originated from the acoustic nerve in four patients and from the trigeminal nerve in two. Four cases were accompanied by the sudden occurrence of clinical symptoms such as headache, double vision, and hemisensory or motor disturbance. The maximum diameter of the tumors ranged from 2.8 to 3.8 cm (average, 3.1 cm). Histological examinations showed massive hemorrhage and increased vascularity, with dilated, thin-walled vessels, in all cases. The size of the tumor and the increase in vascularity with dilated, thin-walled vessels within neurinomas are important pathogenetic factors of hemorrhage. When sudden onset of symptoms or rapid worsening of chronic symptoms occurs in neurinomas, intratumoral or subarachnoid hemorrhage should be considered as a possible cause, and magnetic resonance imaging can be an important tool in obtaining correct diagnosis. PMID- 1407423 TI - Proliferative characteristics of juvenile pilocytic astrocytomas determined by bromodeoxyuridine labeling. AB - Bromodeoxyuridine (BUdR) labeling studies were performed to characterize the biological and clinical behavior of 50 juvenile pilocytic astrocytomas (JPAs) from 47 patients. Each patient received an i.v. infusion of BUdR before tumor resection; the excised tumor specimens were stained by the immunoperoxidase method with anti-BUdR monoclonal antibody to determine the BUdR labeling index (LI), or percentage of S-phase cells. The BUdR LI ranged from 0.22 to 4.3% (less than 1% in 34 and greater than or equal to 1% in 16; mean +/- SE, 1.05 +/- 0.13%). Tumors from younger patients often had higher LIs, but as the age of the patients increased, the frequency of tumors with LIs greater than or equal to 1% decreased. Tumors from male patients had higher LIs than those from female patients (1.36 +/- 0.20% [SE] vs. 0.75 +/- 0.13%; P less than 0.01), and tumors in the cerebellum had higher LIs than those in the hypothalamus (1.39 +/- 0.24% vs. 0.87 +/- 0.15%; P less than 0.05). The LI did not correlate with the gross appearance of the tumor (solid or cystic) or with outcome after the initial diagnosis. Overall, there was no difference in the LIs of primary and recurrent tumors. Four tumors (3 primary and 1 recurrent) that recurred after subtotal resection had a higher mean LI than 32 tumors that did not recur after subtotal resection (2.6 +/- 0.7% vs. 0.74 +/- 0.09%; P less than 0.005). None of 14 totally resected tumors (mean LI, 1.3 +/- 0.2%) has recurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407424 TI - Transcranial color-coded real-time sonography in the evaluation of intracranial neoplasms and arteriovenous malformations. AB - Transcranial color-coded real-time sonography (TCCS) was performed in 57 patients with primary intracranial brain tumors (n = 49) or arteriovenous malformations (n = 8) to evaluate its diagnostic potential. In 46 patients (81%), lesions could be identified employing this technique. In 7 patients, transcranial ultrasound examination was not feasible because of bone thickness; in the remaining 4 patients, the tumor was indistinguishable from adjacent brain tissue despite sufficient insonation, suggesting that these neoplasms are isoechogenic. The sonographic features of brain tumors were very similar: a hyperechogenic matrix of the lesion was interspersed by hypoechogenic pixels. Larger hypoechogenic areas (0.5-1 cm) gave evidence of tumor necrosis. Differences between the findings of TCCS and computed tomography concerning tumor size were found in 7 patients, in whom TCCS revealed an area of smaller extension within the corresponding hypodense area on the computed tomographic scan. Perifocal brain edema could not be detected by ultrasound examination. In 13 patients, a thin, hypoechogenic peritumoral halo was disclosed that did not correlate with perifocal brain edema identified by computed tomography and that may have been due to compression of adjacent parenchyma. In patients with arteriovenous malformations, TCCS permitted the identification of the main feeders, the nidus, and the draining venous system by color-coded depiction of intravascular blood flow. In conclusion, TCCS is an additional method for initial diagnosis and highly suitable for follow-up in tumor patients and provides valuable information about tissue characteristics and blood flow. PMID- 1407425 TI - The prognostic value of somatosensory and motor evoked potentials in comatose patients. AB - Somatosensory and motor evoked potentials (SEP and MEP) were examined in a total of 213 patients in traumatic (n = 140) and nontraumatic (n = 73) coma. It was the aim of this study to compare the prognostic value of MEP elicited by both electrical and magnetoelectric transcranial stimulation with the use of SEP alone. According to the presence or absence of responses and the duration of central conduction time, SEP and MEP obtained during Days 1 through 3 after the onset of coma were divided into four categories and correlated with the outcome of the patients, as assessed by the Glasgow Outcome Scale. Our results clearly show that in terms of prognostic value, SEP are superior to MEP, with normal findings indicating a favorable outcome and absent responses an unfavorable outcome. On the other hand, patients with normal electromyographic responses after both electrical and magnetoelectric stimulation had favorable and unfavorable outcomes about equally. Thus, unlike SEP, normal MEP do not allow any prognostic conclusions. Only the bilateral absence of MEP in response to electrical stimulation was a definitely unfavorable prognostic sign because all of these patients died. In contrast, with magnetoelectric stimulation, neither normal nor absent responses allowed any prognostic conclusions. Therefore, the prognostic value of electrically evoked motor responses is limited, and magnetoelectric stimulation cannot be recommended in this context. PMID- 1407426 TI - Severe head injury in children: experience of the Traumatic Coma Data Bank. AB - The outcome at discharge, 6 months, and 1 year after they had sustained severe head injuries was investigated in children (0-15 yr old at injury) who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank. Of 103 eligible children, the quality of recovery was assessed by the Glasgow Outcome Scale (GOS) at 6 months after injury in 92 patients (86% of series) and at 1 year in 82 patients (73% of series). The lowest post-resuscitation Glasgow Coma Scale score and pupillary reactivity were predictive of the 6-month GOS as were their interaction. Analysis of the first computed tomographic scan disclosed that bilateral swelling with/without midline shift was related to a poor outcome as was the presence of mass lesions. Comparison of age-defined subgroups of patients revealed that outcome was poorest in the 0- to 4-year-old patients, as reflected by their mortality, which increased to 62% by 1 year. Distinctive features of the injuries in the 0- to 4 year-olds included evacuated subdural hematomas (20% of patients) and hypotension (32% of patients). The most favorable outcome was attained by 5- to 10-year-olds (2/3 had a good recovery by 1 yr), whereas the GOS distribution of adolescents was intermediate between the children and adults. In summary, the GOS data reflect heterogeneity in the quality of outcome after severe head injury depending on age, neurological indices, and computed tomographic scan diagnostic category. PMID- 1407427 TI - Management of symptomatic chronic extra-axial fluid collections in pediatric patients. AB - The records of 103 pediatric patients having symptomatic chronic extra-axial fluid collections treated at Children's Hospital of Los Angeles from 1977 to 1988 were reviewed. Patients were treated with observation, serial percutaneous needle drainage, drainage through burr holes, drainage into a closed external drainage system, or subdural to peritoneal shunt. If the initial treatment was not effective, additional forms of treatment were instituted. Shunts, ultimately used in 73% of the patients, proved to be the most effective treatment. Of the group with shunts, the extra-axial fluid was unilateral in 20% and bilateral in 80%. In those patients with bilateral effusions, no difference in efficacy of shunts was seen in patients treated with bilateral versus unilateral shunts. Of the 75 patients with shunts, 12% required a shunt revision for progressive or recurrent symptoms. Shunt infections occurred in 3% of the patients, necessitating removal of the shunt and treatment with antibiotics. Eosinophilia in the subdural fluid was associated with shunt obstruction requiring revision. The shunt was never removed in 51% of patients with no untoward effects. This study demonstrates that the most efficacious treatment of symptomatic chronic extra-axial fluid collections in children is a unilateral subdural to peritoneal shunt. The shunt need not be removed after resolution of the fluid collections. PMID- 1407428 TI - Split cord malformation: Part I: A unified theory of embryogenesis for double spinal cord malformations. AB - Much confusion still exists concerning the pathological definitions and clinical significance of double spinal cord malformations. Traditional terms used to describe the two main forms of these rare malformations, diastematomyelia and diplomyelia, add to the confusion by their inconsistent usage, ambiguities, and implications of their dissimilar embryogenesis. Based on the detailed radiographic and surgical findings of 39 cases of double cord malformations and the autopsy data on two other cases, this study endorses a new classification for double cord malformations and proposes a unified theory of embryogenesis for all their variant forms and features. The new classification recommends the term split cord malformation (SCM) for all double spinal cords. A Type I SCM consists of two hemicords, each contained within its own dural tube and separated by a dura-sheathed rigid osseocartilaginous median septum. A Type II SCM consists of two hemicords housed in a single dural tube separated by a nonrigid, fibrous median septum. These two essential features necessary for typing, the state of the dural tube and the nature of the median septum, do not ever overlap between the two main forms and can always be demonstrated by imaging studies so that accurate preoperative typing is always possible. All other associated structures in SCM such as paramedian nerve roots, myelomeningoceles manque, and centromedian vascular structures frequently do overlap between types and are not reliable typing criteria. The unified theory of embryogenesis proposes that all variant types of SCMs have a common embryogenetic mechanism. Basic to this mechanism is the formation of adhesions between ecto- and endoderm, leading to an accessory neurenteric canal around which condenses an endomesenchymal tract that bisects the developing notochord and causes formation of two hemineural plates. The altered state of the emerging split neural tube and the subsequent ontogenetic fates of the constituent components of the endomesenchymal tract ultimately determine the configuration and orientation of the hemicords, the nature of the median septum, the coexistence of various vascular, lipomatous, neural, and fibrous oddities within the median cleft, the high association with open myelodysplastic and cutaneous lesions, and the seemingly unlikely relationship with fore and midgut anomalies. The multiple facets of this theory are presented in increasing complexity against the background of known embryological facts and theories; the validity of each facet is tested by comparing structures and phenomena predicted by the facet with actual radiographic, surgical, and histopathological findings of these 41 cases of SCM. PMID- 1407429 TI - Split cord malformation: Part II: Clinical syndrome. AB - Thirty-nine patients with split cord malformations (SCM) were studied in detail with respect to their clinical, radiographic, and surgical findings as well as their outcome data. Eight patients were adults and 31 patients were children. According to the classification endorsed by Part I of the SCM study, 19 patients had Type I SCM (6 adults and 13 children), 18 patients had Type II SCM (2 adults and 16 children), and 2 patients had composite SCM with both lesion types situated in tandem. Six SCMs were cervical, 2 were thoracic, and 31 were in the lumbar region. All 8 adults had pain and progressive sensorimotor deficits at diagnosis. Only 16 of the 31 children had symptoms, and among these, 14 had progressive sensorimotor deficits, but only 6 had pain. The difference in the clinical picture between adults and children is similar to that described in the tethered cord syndrome, except for left-right functional discrepancy, which was prominent in 8 children with SCM but rarely seen in tethered cord syndrome due to other causes. Cutaneous manifestations of either occult or open dysraphic states were present in all but 3 patients; hypertrichosis was by far the best predictor of an underlying SCM, being found in 56% in the series. Neurological deterioration in SCM was independent of the lesion type: the Type I:Type II ratio for symptomatic progression was 13:11. It was also independent of the location of the lesion: 67% of patients with cervical SCMs had symptomatic progression versus 64% of patients with thoracolumbar lesions. High-resolution, thin cut, axial computed tomographic myelography using bone algorithms was more sensitive than magnetic resonance imaging in defining the anatomical details of the SCM. Radiographic classifications of the SCM, using the nature of the median septum and the number of dural tubes as criteria, was always possible without ambiguity. However, whereas every Type I bone septum was identified preoperatively, only 5 Type II fibrous septa were revealed by preoperative imaging, even though a fibrous septum and/or other fibroneurovascular bands were found tethering the hemicords in every Type II case at surgery. Complete imaging studies also showed that all lumbar SCMs had low-lying coni and at least one additional tethering lesion besides the split cords, whereas only 1 of 7 cervical and high thoracic SCMs had a low conus and a second tethering lesion. The surgical goal for SCM was release of the tethered hemicords by eliminating the bone spurs, dural sleeves, fibrous septa, or any fibroneurovascular bands (myelomeningoceles manque) that might be transfixing the split cord. Type I cases were technically more difficult and had a slightly higher surgical morbidity than Type II cases, especially if an oblique bone septum had asymmetrically divided the cord into one larger hemicord and one smaller, hence, very delicate, hemicord.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1407430 TI - Lateral cervical spine dislocation and vertebral artery injury. AB - Although anterior and posterior traumatic displacement of cervical vertebrae are commonly noted, and the devastating neurological deficits associated with these injuries have been amply defined, lateral displacement with fractures has been rarely recognized, and the clinical significance of this injury has been overlooked. This report describes five cases of cervical spine fractures with lateral dislocation. All patients had lateral and anteroposterior cervical spine radiographs as well as cervical angiography or postmortem study demonstrating either complete occlusion or significant impairment of flow of the vertebral arteries. Two cases had traumatic vertebral artery occlusion with secondary medullary and cerebellar infarction resulting in the patient's death. Vertebral artery injury apparently is not uncommon in this particular type of fracture. The diagnosis of these vascular injuries may require angiography or magnetic resonance angiography. A vertebral occlusion or dissection is a problem of considerable complexity, requiring individualized management depending on the patient's symptomatology, location and nature of the injury, and time lapsed since the injury. PMID- 1407431 TI - High-resolution magnetic resonance imaging of experimental spinal cord injury in the rat. AB - The ability of magnetic resonance imaging (MRI) to display the anatomic changes after spinal cord injury in the rat were examined in postmortem specimens. With the clip compression technique, acute spinal cord injuries of three grades of severity were produced in adult male rats. One hour after injury, during which time physiological parameters were measured and maintained within the normal range, the rats were killed by transcardiac perfusion of formalin. The vertebral column containing the cervical and upper thoracic segments was excised and, after further formalin fixation, 20 contiguous MRI scans centered on the injury site were obtained using a spin-echo imaging sequence. The volume of signal acquisition for each image was 15 x 15 x 1.0 mm thick. The spinal cords were then removed from the vertebral column, sectioned, and stained for histological examination. Ten-micrometer serial sections of each cord were examined microscopically. MRI scans and microscopic sections at comparable levels were examined to determine the quality of anatomical detail and spatial resolution of the MRI scans. MRI scans with resolution of about 75 microns per pixel edge were obtained. At the site of injury, there was disruption of the normally well demarcated gray-white interface and variable areas of low signal intensity. Because of the resolution achieved, it was possible to determine that these low signal intensity areas were post-traumatic hemorrhages. Indeed, hemorrhages with dimensions of the order of 100 microns were detected on the MRI scans. Furthermore, by examining the serial sections of the cord, the extent of the injury along the cord could be determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407432 TI - Origins and conducting pathways of motor evoked potentials elicited by transcranial magnetic stimulation in cats. AB - Spinal cord motor evoked potentials (MEPs-S) were elicited in cats by transcranial magnetic stimulation. The MEPs-S recorded from the epidural electrode at the first lumbar (L1) level consisted of four negative peaks (N1, 2.56; N2, 3.19; N3, 4.06; N4, 4.99 ms) followed by small, multiphasic waves. The mean conduction velocities of N1-N3 of the MEPs-S were calculated to be 90 to 115 m/s, which is consistent with extrapyramidal tract activation. A direct brain stem electrical stimulation and sequential transection of the spinal cord studies showed that N1-N3 of the MEPs-S originated primarily from the brain stem and conducted in the ventral funiculus of the spinal cord, which corresponded to the extrapyramidal tracts (e.g., the reticulospinal and vestibulospinal tracts). We also showed that N1 and N2 of the MEPs-S originated mainly from the lower medulla or upper cervical and that N3 originated from the lower pons or upper medulla (vestibular nucleus). On the other hand, N4 of the MEPs-S had a conduction velocity of 70 m/s, which disappeared by ablation of the sensorimotor cortex and pyramidotomy. A dorsal hemisection of the spinal cord, resulting in the disappearance of N4 of the MEPs-S, indicated that it conducted in the dorsolateral funiculus of the spinal cord. These results suggest that N4 of the MEPs-S originates from the sensorimotor cortex and conducts in the lateral corticospinal tract. MEPs-S by transcranial magnetic stimulation in cats constituted complex responses in both the pyramidal and extrapyramidal tracts. PMID- 1407433 TI - Successful treatment of a malignant rat glioma with cytotoxic T lymphocytes. AB - Brain tumors are highly resistant to therapy. Their diffuse infiltrative nature and the relative inaccessibility of brain tissue to blood and lymph are barriers to surgical and cytotoxic treatments alike. The purpose of this study was to produce immune cells specifically reactive with an anaplastic rat glioma (RT2) and determine whether those cells could affect tumor progression in the brain. RT2-specific cytotoxic cells were prepared by priming rats in vivo with RT2 tumor cells and Corynebacterium parvum and stimulating the primed lymphocytes in vitro with irradiated RT2 tumor cells and interleukin-2 (IL-2). Cultured cells exhibited a high level of cytotoxicity against RT2, but not C6 (an allogeneic glioma), 3M2N (a syngeneic mammary tumor), or CSE (a syngeneic fibrosarcoma) tumor cells. To generate a model for therapy, rats were injected intracerebrally with RT2, generating progressing brain tumors, which killed untreated rats in approximately 2 weeks. To test the therapeutic potential of the effector cells, tumor-bearing rats were treated by intravenous injection of lymphocytes on Day 5 of tumor growth. Treated rats also received a 5-day course of systemic IL-2 beginning on Day 5. Treatment with IL-2 alone, RT2-primed spleen cells, or RT2 primed spleen cells stimulated in vitro with C6 did not affect rat survival. However, tumor-bearing rats treated with RT2-stimulated lymphocytes exhibited increased survival or were cured. Systemic IL-2 was an essential adjunct, because survival was not affected by treatment with effector cells alone. Therapy initiated on Day 8 of tumor progression lacked effect on survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407434 TI - Mechanism of interferon gamma-induced protection of human gliosarcoma cells from lymphokine-activated killer lysis: division of lymphokine-activated killer cells into natural killer- and T-like cells. AB - The mechanism by which interferon gamma (IFN-gamma) decreases the susceptibility of the established cultured gliosarcoma line Gl-1 to lymphokine-activated killer (LAK) lysis was analyzed. The results of monolayer depletion and lectin-dependent cellular cytotoxicity assays by LAK cells revealed that the resistance to LAK lysis of IFN-gamma-treated Gl-1 cells is manifested at the stage of LAK cell target recognition alone. We have also divided LAK cells into populations of phenotypically natural killer (NK)- and T-like cells with monoclonal antibodies and complement, respectively. We have used these cells to examine the mechanism of IFN-gamma-induced protection of Gl-1 cells from LAK lysis in cold target inhibition, monolayer depletion, and direct binding assays. The results revealed that NK-like cells do not recognize IFN-gamma-treated Gl-1 cells as efficiently as they do untreated targets, whereas T-like cells show the opposite tendency. In conclusion, we have demonstrated that the IFN-gamma induced protection of tumor cells from LAK lysis is predominantly regulated by the target recognition of NK like cells. On the other hand, IFN-gamma-treated tumor cells may bind to T-like cells but fail to trigger them to initiate further stages for lysis as effectively as NK-like cells. PMID- 1407435 TI - Ganglioside composition and its relation to clinical data in brain tumors. AB - The ganglioside composition of 15 cases of meningioma, 15 cases of astrocytoma, 5 cases of neurinoma, 4 cases of ependymoma, 3 cases of metastatic brain tumor and 1 case each of mixed glioma, oligodendroglioma, medulloblastoma, embryonal carcinoma, and cultured glioma cell line were analyzed by thin-layer chromatography. The GM2, GD3, and GD2 content of the tumors was determined using specific monoclonal antibodies (MAb). Cases were grouped according to the difference in ganglioside pattern and various clinical features. In meningiomas and astrocytomas, GM3 and GD3 were the major gangliosides. The tumor content of the rather simple gangliosides (GM3, GM2, GD3, GD2) increased or was almost equal to that of normal tissue (leptomeninges tissue in the case of meningiomas, and brain tissue in the case of astrocytomas), while the tumor content of complex gangliosides (GM1, GD1a, GT1a, GT1b) decreased as compared with normal tissue. The GM3 content of meningiomas increased in middle-aged patients, who comprised the majority of the patients with these tumors. The GD2 content decreased in middle-aged patients with initial symptoms of meningioma within a year. The GM3 content of astrocytomas decreased in patients who underwent radiotherapy. The amount of GM3 and GD3 increased in small tumors. GM3 may be related to the early proliferative stage. The ganglioside patterns of brain tumors are shown in this study to differ according to clinical features and also to be changeable in their clinical courses. PMID- 1407436 TI - Effect of leukotriene antagonist on experimental delayed cerebral vasospasm. AB - Experimental delayed cerebral vasospasm was produced in 16 adult mongrel dogs by the "two-hemorrhage" method of intracisternal injections of autologous arterial blood. Group 1 was a control group. Group 2 was a treatment group that received an intravenous injection of ONO-1078, a novel potent leukotriene antagonist, once a day for 7 days just after the first cisternal injection of the blood. Angiography was performed on Days 0 and 7, and the cerebrospinal fluid levels of leukotriene C4 (LTC4) were measured on Days 0, 3, and 7. The cisternal levels of LTC4 increased after subarachnoid hemorrhage in both groups. But the cerebrospinal fluid levels of LTC4 in the treatment group were significantly lower than those in the control group (P less than 0.05). The angiographic vasospasm after subarachnoid hemorrhage was partially prevented with the treatment of intravenous injections of ONO-1078 (P less than 0.001). These results suggest that LTC4 may play a role in the pathogenesis of delayed cerebral vasospasm, directly or indirectly, and ONO-1078 may have a therapeutic effect on the prevention of the development of delayed cerebral vasospasm. PMID- 1407437 TI - Successful treatment of intracerebral hydatid cysts with albendazole: case report and review of the literature. AB - Experience with the use of the drug albendazole in the management of cerebral hydatid disease is limited. We report a 33-year-old woman who was harboring multiple cerebral hydatid cysts and who was treated successfully with albendazole. No other treatment was used. The efficacy and the few reversible side effects of the drug are discussed, and the literature is reviewed. PMID- 1407438 TI - Continual intracavitary administration of amphotericin B as an adjunct in the treatment of aspergillus brain abscess: case report and review of the literature. AB - Aspergillus brain abscess is often a fatal disease, regardless of the mode of therapy. Most often seen in the compromised host, it is notoriously refractory to systemic antifungal agents and intrathecal antimycotics. Even with radical surgical debridement, only 13 patients, including the present case, have survived longer than 3 months after being treated for aspergillus brain abscess or granuloma. Studies have shown poor penetration of amphotericin B into the brain and cerebrospinal fluid. One way to achieve therapeutic levels of the agent near the abscess is through the direct introduction of the agent into the abscess site via an indwelling catheter. In the present case, a woman with an aspergillus abscess of the left temporal lobe was treated by a combination of systemic agents, radical debridement, and local therapy, resulting in a cure with a follow up of 6 years. This is the first reported instance of the use of long-term, local antifungal therapy delivered to the area of the abscess cavity, using a closed reservoir system, and this patient is only the second renal transplant patient reported to have survived aspergillus brain abscess. This form of treatment produced no untoward long-term side effects or neurological sequelae. Local irrigation with antifungal agents should be considered in conjunction with systemic antifungal drugs and drainage and/or debridement in cases of fungal intracerebral aspergilloma. This technique may also prove useful with other fungal brain lesions. PMID- 1407439 TI - Traumatic subdural hygroma: pathology and meningeal enhancement on magnetic resonance imaging. AB - Five patients with traumatic subdural hygroma are reported with reference to its pathology and meningeal enhancement on magnetic resonance imaging. Hygromas showed initially iso- and, later, high intensity on both T1- and T2-weighted images compared with the intensity of the cerebrospinal fluid. In all cases of the thick hygromas, magnetic resonance imaging with gadolinium diethylene triamine-pentaacetic acid showed meningeal enhancement. Intravenously injected radioisotope immediately flowed into the hygromas, but computed tomographic cisternography and gross inspection during the surgery showed no evidence of an influx of cerebrospinal fluid into the hygromas. Microscopic examination of the enhanced meninges revealed vascularized neomembrane with numerous fenestrations and pinocytosis underneath the dura mater. It is suggested from these data that the subdural neomembrane is associated with the development of the traumatic subdural hygromas. Meningeal enhancement would be useful to clarify the growing mechanism of traumatic subdural hygromas. PMID- 1407440 TI - Cerebral hemorrhage from amyloid angiopathy and coronary thrombolysis. AB - Coronary thrombolysis with streptokinase or tissue plasminogen activator is useful for the treatment of acute myocardial infarction in selected patients. This treatment is associated with local hemorrhagic complications and age-related cerebral hemorrhage. Coronary thrombolysis is contraindicated in patients with transient cerebral ischemia and stroke, arterial hypertension, cerebral trauma, cerebral aneurysms, and arteriovenous malformations, because of the risk of cerebral hemorrhage. We report the occurrence of a cerebral hemorrhage related to cerebral amyloid angiopathy in a patient who underwent thrombolysis and treatment with heparin for acute myocardial infarction. Despite normal coagulation parameters, the cerebral hematoma enlarged over 36 hours, as documented by sequential computed tomographic scans, to produce significant mass effect, which prompted surgical evacuation. Histological examination of the resected specimen demonstrated the strong affinity for Congo red and yellow-green birefringence that are characteristic of cerebral amyloid angiopathy. Hemostasis was difficult to achieve, as the divided or disrupted amyloid-laden cortical vessels failed to vasoconstrict, their contractile elements replaced by amyloid beta protein. The patient died of recurrent myocardial ischemia 3 days postoperatively. The incidence of cerebral amyloid angiopathy increases with advancing age. It must be considered as a potential source of cerebral hemorrhage in elderly patients undergoing thrombolysis for cardiac ischemia. Such an occurrence presents a difficult challenge because cardiac function is compromised, the coagulation profile may be altered, the cerebral hematoma is life threatening, and intracranial hemostasis is difficult to achieve. PMID- 1407441 TI - Carotid-cavernous fistula caused by a ruptured intracavernous aneurysm: endovascular treatment by electrothrombosis with detachable coils. AB - A case of carotid-cavernous fistula caused by a ruptured intracavernous aneurysm is reported. The fistula was treated with electrothrombosis by the detachment of two platinum coils into the aneurysm via an endovascular transvenous approach; the fistula was closed, and the patient has recovered completely. The advantages of using electrodetachable platinum coils include thrombogenicity, controllable deposit, radiopacity, and biocompatibility. PMID- 1407443 TI - Anatomy of the sympathetic pathways in the carotid canal. PMID- 1407442 TI - Transcallosal, transventricular approach to a basilar apex aneurysm. AB - A new approach to the basilar apex in a patient with a megadolichobasilar anomaly and an abnormally rostral basilar apex aneurysm is described. The details of the surgical approach and the advantages and limitations of this transcallosal, interseptal approach are described. PMID- 1407444 TI - Cerebral arteriovenous malformations: factors influencing surgical difficulty and outcome. PMID- 1407445 TI - Acoustic neurinoma in the elderly: factors predictive of postoperative outcome. AB - The authors present the results of acoustic neurinoma surgery in 61 elderly patients (age, > or = 65 years). All the patients were operated upon via the lateral suboccipital approach. Complete tumor removal was achieved in all but two patients. There was no operative mortality. Fifty-seven patients (93%) were independent of nursing assistance at the time of discharge from the hospital. Preservation of the facial nerve was achieved in 95% of the patients, and hearing was preserved in 41%. A risk analysis identified three factors exerting a significant influence on the outcome in these cases: the American Society of Anesthesiology score, the preoperative Karnofsky score, and the size of the tumor. The patients' age was not correlated with the postoperative outcome. These results suggest that, in the majority of elderly patients with acoustic tumors, complete tumor removal can be achieved safely and with minimal postoperative morbidity. Preoperative clinical, neurological, and radiological factors can be helpful in the selection of patients for surgical treatment and may predict postoperative outcome. PMID- 1407446 TI - Magnetic resonance imaging of tuberculum sellae meningiomas: preventing preoperative misdiagnosis as pituitary macroadenoma. AB - Despite recent advances in neurodiagnostic imaging, it may be difficult to differentiate tuberculum sellae meningiomas from pituitary macroadenomas preoperatively. Magnetic resonance (MR) imaging has supplanted computed tomography as the imaging modality of choice for sellar and parasellar lesions, but unenhanced MR imaging does not reliably distinguish between all tuberculum sellae meningiomas and pituitary macroadenomas. Accurate differentiation between these alternative diagnoses of a suprasellar mass is important because a tuberculum sellae meningioma always requires a craniotomy, whereas a transsphenoidal route is preferred for removing most pituitary macroadenomas. The gadolinium-enhanced MR images of seven patients with tuberculum sellae meningioma and seven with pituitary macroadenoma were reviewed retrospectively. Although no specific radiological feature was pathognomonic, a combination of several features allowed the correct diagnosis in all cases. Three characteristics of tuberculum sellae meningiomas distinguish them from pituitary macroadenomas: 1) bright homogeneous enhancement with gadolinium, as opposed to heterogeneous, relatively poor enhancement; 2) a suprasellar rather than a sellar epicenter of tumor; and 3) tapered extension of an intracranial dural base. Each of these findings can be subtle, but careful examination of gadolinium-enhanced, high quality, thin section coronal and sagittal MR images of the parasellar region for this constellation of findings will allow the correct preoperative diagnosis in patients with either of these tumors. PMID- 1407447 TI - Surgical strategies in the treatment of symptomatic osteomas of the orbital walls. AB - We present a series of 19 surgically treated osteomas involving the orbital walls. Eight were localized at the junction of the frontal sinus and orbital roof, three were frontoethmoidal, two were of the orbital roof, one of the lateral wall, one of the orbital floor, and four involved all the walls of the orbit and were termed panorbital. All tumors at the junction of the frontal sinus and the orbital roof as well as those originating from the orbital roof proper were removed by frontal craniotomy. In the three that were frontoethmoidal, osteotomies were performed. Lateral and inferior orbitotomies were done when the corresponding orbital walls were affected. The four panorbital osteomas required large frontotemporal craniotomies in association with superolateral orbitotomy and zygomatic and/or malar osteotomy, when necessary. Satisfactory cosmetic and functional results were obtained in all but two cases of panorbital osteomas, in which the neurological deficit worsened after surgery. We discuss the choice of the various approaches described, with reference to the relevant literature. PMID- 1407448 TI - Treatment and survival of low-grade astrocytoma in adults--1977-1988. AB - A retrospective review of the records of the Division of Neuropathology at the New York University Medical Center between 1977 and 1988 revealed 53 cases of adult supratentorial astrocytomas. Fifty were fibrillary, and three were gemistocytic. Two additional patients had pilocytic tumors and were not included in the study. The majority of patients had either a subtotal (64%) or gross total resection (19%). Biopsy (17%) was performed for deep-seated lesions and for those lesions confined to eloquent cortex. Forty-eight patients (91%) received postoperative radiation therapy. The median survival was 7 1/4 years with a 5 year survival of 64%. Multivariate regression analysis demonstrated that the most important prognosticators for improved survival were young age, absence of contrast enhancement of the original tumor on computed tomography (CT) and the performance status of the patient. Patients with hemispheric tumors died from dedifferentiation into an anaplastic astrocytoma or a glioblastoma multiforme, with a median time to recurrence of 4.5 years from the original surgery. Survival from the time of recurrence was 12 months. Subsequent operations confirmed progression towards malignancy in six of seven (86%) recurrent tumors. CT contrast enhancement of the original tumor was associated with a 6.8-fold increase in risk for later recurrence. Patients with thalamic tumors (six patients) had a poor prognosis with a median survival of less than 2 years. A review of their CT scans suggest that four died of progressive low-grade disease; however, confirmatory autopsy data were available for only one patient. This study supports others that have shown improved survival for adult patients with astrocytomas treated in the CT era. PMID- 1407449 TI - Radiotherapy for pediatric brain stem glioma: radiation dose, response, and survival. AB - An analysis of 39 patients under 20 years of age with brain stem glioma treated with radiotherapy between 1977 and 1991 was undertaken. Twenty-eight (71.2%) of the patients responded well to initial radiotherapy, and 11 (28.8%) responded poorly. Median survival for the total patient population was 10 months. Response rates and median survivals were influenced by radiation dose: 45.5% and 9 months at doses less than 4499 cGy (n = 11), 83.3% and 13 months at doses between 4500 and 5499 cGy (n = 12), 66.7% and 11.5 months at doses between 5500 and 6499 cGy (n = 9), and 100% and 10 months at doses more than 6500 cGy (n = 7). Multivariate analysis revealed the response to initial radiotherapy was the only predictor of survival with radiation doses up to 6499 cGy. Four of the patients who responded well demonstrated radiological and/or histological calcification within or around the tumor at the time of clinical deterioration. Radiation injury was confirmed in two autopsy cases. The possibility that intratumoral radiation injury causes clinical deterioration is suggested. PMID- 1407450 TI - Pathological status of the mesial temporal lobe predicts memory outcome from left anterior temporal lobectomy. AB - This investigation tested the hypothesis that the degree of impairment to memory function caused by an anterior temporal lobectomy (ATL) is inversely related to the pathological status of the resected hippocampus. Specifically, the greatest risk to postoperative memory function should be to patients with no or minimal hippocampal sclerosis, i.e., those with a functional hippocampus. Forty patients who underwent a partial resection of the left (n = 21) or right (n = 19) anterior temporal lobe were administered tests of immediate and delayed verbal and figural memory, both preoperatively and 6 months postoperatively. The degree of postoperative impairment in memory function was then investigated as a function of the degree of hippocampal sclerosis, as determined by a standardized procedure. For a left ATL, an absence or mild degree of hippocampal sclerosis was associated with significantly greater postoperative impairment of both verbal and figural memory, compared with patients with moderate or marked sclerosis. No statistically significant relationship was noted for patients who underwent a right ATL, but the findings were in the same direction for five of six memory measures. It may be possible to predict and avoid surgically induced impairment of memory function among patients who undergo left ATL through the use of preoperative hippocampal volumetric magnetic resonance imaging. Better clinical tests of right hippocampal function are needed to predict the outcome for patients who undergo a right ATL. PMID- 1407451 TI - Cerebral vasodilation after the thermocoagulation of the trigeminal ganglion in humans. AB - The resulting changes in the regional cerebral blood flow of 18 patients suffering from idiopathic trigeminal neuralgia and treated by selective thermocoagulation of the trigeminal ganglion were measured by xenon-133 emission tomography. One hour after thermal stimulation, there was an asymmetric increase (P < 0.05) in cerebral blood flow, with a 14.7% mean increase in the ipsilateral cerebral hemisphere (P < 0.001) and a 12.7% mean increase in the contralateral side (P < 0.01). The increase in regional cerebral blood flow was not uniform but was most marked in the ipsilateral middle cerebral artery territory (P < 0.001). There was a slight decrease in cerebellar blood flow, but the reduction in the ipsilateral cerebellar lobe was less than that in the contralateral lobe (P < 0.01). The topography of the most significant changes coincided with that of the innervation of the cerebral vessels by the trigeminal nerve. Several mechanisms are involved in the increase in regional cerebral blood flow, including overall nonspecific activation of the central nervous system and local mechanisms associated with the trigeminal-vascular system. PMID- 1407452 TI - Changes in human intracerebral temperature in response to different methods of brain cooling. AB - The rectal, epidural, and intraventricular temperatures were continuously monitored in 10 seriously injured and unconscious patients admitted for neurosurgical intensive care. Different attempts were made to lower their brain temperatures. Isolated head cooling, whether with frozen liquid (Hypotherm Gel Kap; Flexoversal, Hilden, Germany) or a cooling helmet, had very limited effect. Nasopharyngeal cooling had no effect. During barbiturate coma, a considerable increase in brain temperature was observed. The administration of paracetamol was the single most effective method by which to lower brain temperature, at times by 2 degrees C and usually with a concomitant decrease in the temperature gradient between the rectum and the brain. However, in order to achieve a lasting reduction of brain temperature to 35 degrees C, we had to use a combination of head cooling and intensive whole-body cooling. PMID- 1407453 TI - Intraventricular hemorrhage in blunt head trauma: an analysis of 43 cases. AB - Before the advent of computed tomography, intraventricular hemorrhage (IVH) from any source was thought rare and invariably fatal. Although intraventricular blood is readily identifiable with computed tomography, there has been little systematic study of its significance in blunt head trauma. Forty-three patients with traumatic IVH were prospectively identified in 1 year at Harborview Medical Center (University of Washington). Most were victims of motor vehicle accidents and suffered severe head injuries. IVH occurred alone in two patients; superficial contusions and subarachnoid hemorrhage were the most common associated finding. Blood was present in only one or both lateral ventricles in 25 patients; only the 3rd or 4th ventricles in 4 and all ventricles in 14 instances. There were 3 intracerebral hematomas and 14 basal ganglion hemorrhages. All of the former and half of the latter communicated with the adjacent lateral ventricle. Extra-axial hematomas appeared more common when only the lateral ventricles were involved, whereas corpus callosum or brain-stem hemorrhage appeared more likely when all the ventricles were involved. Acute hydrocephalus was rare, and ventricular drainage was needed in only four cases. Intracranial pressure (ICP) was elevated (> 15 mm Hg) in 46% of patients. The amount of IVH was related inversely with the Glasgow Coma Scale, but not with increased ICP. The presence of IVH indicated a poor outcome, with only half of the patients being independent at a 6-month follow-up. Poor outcome was associated with increasing age, low admission Glasgow Coma Scale, the presence of space occupying lesions if only the lateral ventricles were involved, and hemorrhage in all four ventricles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407454 TI - The education of a neurosurgeon: the two cultures revisited. PMID- 1407455 TI - Effect of nicardipine on basilar artery vasoactive responses after subarachnoid hemorrhage. AB - The effect of the dihydropyridine calcium antagonist, nicardipine, on the vasoactive responses of the basilar artery was investigated after subarachnoid hemorrhage (SAH). Forty-five rabbits were separated into one control group and four groups receiving SAH (nine animals each). The SAH was induced by injecting 5 ml of autologous arterial blood into the cisterna magna. SAH animals were subjected to one of the following: 1) no treatment; 2) intravenous (i.v.) saline infusion (vehicle); 3) i.v. infusion of low-dose nicardipine (0.01 mg/kg/hr), or 4) i.v. infusion of high-dose nicardipine (0.15 mg/kg/hr). The i.v. infusions were started immediately after SAH and continued for 48 hours. Serotonin (5-HT) (10(-8) to 10(-5) mol/L) was used to evoke dose-dependent vasoconstriction of isolated rings of the basilar artery 2 days after SAH. Acetylcholine (ACh) (10( 8) to 10(-4)) and adenosine-triphosphate (ATP) (10(-8) to 10(-4) mol/L) were applied after maximal contraction with 5-HT, evoke a dose-dependent vasodilatation. Compared with controls, in animals subjected to SAH serotonin caused similar or slightly larger contractions; nicardipine infusion did not decrease the amount of contraction observed after SAH. ACh and ATP caused significantly less dilatation in animals submitted to SAH than in controls. After high-dose nicardipine, ACh- and ATP-induced dilatations were significantly more pronounced (57% and 68% of initial contractile tone) than in the other animals receiving SAH (36%-39% and 45%-55%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407456 TI - Experimental aspects of cerebrospinal hemodynamics: the relationship between blood flow velocity waveform and cerebral autoregulation. AB - The dynamic relationships among mean flow velocity, its pulsatile amplitude (FVa), cortical cerebral blood flow (CBF), and cerebral perfusion pressure (CPP) were studied in normal rabbits and rabbits with subarachnoid hemorrhage using 8 MHz pulsed transcranial Doppler ultrasound and hydrogen clearance under conditions of systemic hypotension and intracranial hypertension. A two-slope relationship was observed between FVa and CPP with a break point that correlated closely with the lower limit of CBF autoregulation in each animal. Below this CPP break point, FVa varied directly with CPP, and above the break point FVa varied inversely with CPP. In this experimental model, an inverse correlation between FVa and CPP indicates intact CBF autoregulation, whereas loss of that correlation implies exhaustion of autoregulatory reserve. Simultaneous recording and computation of FVa, CPP, and the correlation coefficient between FVa and CPP may be a means of monitoring CBF autoregulation in clinical practice. PMID- 1407457 TI - Relation between protein kinase C and calmodulin systems in cerebrovascular contraction: investigation of the pathogenesis of vasospasm after subarachnoid hemorrhage. AB - The protein kinase C (PKC) and calmodulin systems each play a role in vascular contraction. However, the correlation of these two systems in producing contraction has been unclear. To clarify the pathophysiology of vasospasm after subarachnoid hemorrhage, the authors demonstrated tonic contraction of the cerebral artery in a study of isometric tension, and investigated the correlation of the PKC and calmodulin systems in producing the contraction. To develop better management for vasospasm, they also examined the effect of calmodulin antagonists on tonic contraction. The development of isometric tension in canine basilar arteries was measured, with the following results: 1) tonic contraction was dependent on the PKC system, but initiation of the contraction by the calmodulin system was necessary for the subsequent PKC-dependent tonic contraction; 2) specific calmodulin antagonists like chlorpromazine and pimozide partially inhibited the tonic contraction associated with PKC activation; 3) another calmodulin antagonist, trifluoperazine, inhibited the PKC system as well. On the basis of these results, the authors conclude that the PKC system plays a role in the development of vasospasm. In the early phase of contraction, the calmodulin system contributes to the subsequent fully-activated, PKC-induced tonic contraction. To manage vasospasm, a specific calmodulin antagonist would therefore not be sufficient. Suppression of both the calmodulin and PKC systems with trifluoperazine in the earliest stage of vasospasm is recommended. PMID- 1407458 TI - Protein kinase C activity correlates with the growth rate of malignant gliomas: Part II. Effects of glioma mitogens and modulators of protein kinase C. AB - The proliferation rates of gliomas may be modulated by the protein kinase C (PKC) signal transduction system. The present study was undertaken to further examine the role of PKC system in growth regulation of gliomas in vitro by measurement of PKC activity over various phases of tumor growth and by assessing its potential role as a signal transduction system induced by serum mitogens and the known glioma mitogens epidermal growth factor and fibroblast growth factor. All human glioma lines examined, and the rat glioma C6, displayed high PKC activity relative to nonmalignant glial cells, which correlated with their proliferation rates over their respective growth phase. Frozen surgical human malignant glioma specimens also displayed high PKC activity. The relatively selective PKC inhibitor staurosporine (SP) reduced PKC activity and corresponding growth rates in a dose-related manner. Stimulation of PKC with phorbol esters under different concentrations of serum in the growth medium indicated that the high PKC activity, which correlated with their rapid growth rates, is highly susceptible to down-regulation by these agents. Epidermal growth factor and fibroblast growth factor increased both PKC activity and the growth rate of glioma line A172; addition of SP reduced the growth rate to levels observed in SP-treated control tumors, indicating that PKC may be a common signal transduction system induced by these mitogens. These results implicate PKC as an important signal transduction system regulating glioma growth, and offers a potential target for tumor inhibition. PMID- 1407459 TI - Enhancement of radiosensitivity by tamoxifen in C6 glioma cells. AB - The antiestrogen drug tamoxifen, which is used extensively in the treatment of breast cancer, has also been reported to inhibit the proliferation of some estrogen receptor-negative cell lines, including malignant glioma in vitro. To explore the possible role of tamoxifen in the treatment of malignant glioma, we have investigated its effects on cell growth and radiosensitivity in C6 glioma cells using a colony-forming assay and a tetrazolium-formazan growth rate assay. Pretreatment of C6 cells with tamoxifen resulted in dose-dependent inhibition of cell growth and enhancement of the antitumor effects of ACNU and irradiation. The radiosensitivity of the treated cells was enhanced by the administration of 5 mumol/L of tamoxifen either before and during irradiation or continuously before, during, and after irradiation [37% survival dose (Do) = 2.68 +/- 0.19 and 2.64 +/ 0.04 Gy, respectively, P < 0.01)], as compared with controls (Do = 3.79 +/- 0.25 Gy). In addition, protein kinase C activity was also inhibited by tamoxifen at the concentration in which the radiosensitivity was augmented in C6 cells. Taken together, our results demonstrate a synergistic effect of tamoxifen with radiation on intracellular damage in C6 glioma cells, which may in part be due to the inhibition of protein kinase C, suggesting that tamoxifen serves as a useful agent in combination therapy of glioma. PMID- 1407460 TI - Measurement of local directional pressures in the brain with mass. AB - In order to understand the effects and the direction of pressure transmitted from a mass lesion through various brain structures, miniature strain gauges were inserted in different brain locations in eight anesthetized monkeys. Mass lesions were created by inflating a balloon in either of two locations--subcortical in four animals (Group I) and deep (lateral to the caudate nucleus) in the other four animals (Group II). Anterior-posterior directed pressures were thus measured from a gauge placed in the parietal lobe, and lateromedially directed pressures (LM-dPs) were measured from gauges in the temporal lobe and midbrain. Intracranial pressure, systemic mean arterial pressure, and cerebral blood flow were also monitored. After balloon inflation was begun, temporal changes in pressure were recorded from gauges as percentage increase or decrease from baseline measurements. In both groups, balloon inflation caused a gradual increase in the parietal lobe anterior-posterior directed pressure with a concomitant increase in intracranial pressure and a decrease in cerebral blood flow. The temporal lobe gauge in Group I recorded an initial negative followed by a positive LM-dP with further balloon inflation. In Group II, this gauge recorded a positive LM-dP throughout. The midbrain gauges in both groups recorded an initial positive followed by a negative LM-dP. This reversal in the direction of pressure in the midbrain occurred just before the supratentorial pressure reached a peak and was noted to be concurrent with a sudden rise in mean arterial pressure and a decline in cerebral blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407461 TI - Hemorrhage in a highly vascularized subependymoma of the septum pellucidum: case report. AB - A 63-year-old man was admitted to our hospital because of loss of memory, disorientation, nausea, and urinary incontinence. Cerebral computed tomographic and magnetic resonance imaging scans revealed a tumor with intratumoral hemorrhage affecting the corpus callosum and the septum pellucidum. A partial resection of the tumor was performed, but the patient died the next day from an episode of bleeding. Postmortem examination revealed a highly vascularized subependymoma with acute bleeding in the tumor and in the surrounding brain parenchyma. The importance of considering a highly vascularized subependymoma is noted when a tumor related to the ventricular system is diagnosed. PMID- 1407462 TI - Anterior third ventricle meningioma in an adolescent: a case report. AB - A case of an anterior third ventricular meningioma in a 17-year-old girl is presented. Gross total resection of this tumor with minimal morbidity was accomplished by transcallosal exposure through a frontal craniotomy. A review of the literature implies that surgical morbidity and mortality for the removal of third ventricular meningiomas markedly improved with the use of the operating microscope. Despite advanced imaging capabilities, radiographic analysis of a solid third ventricular mass may not always determine tissue diagnosis. In addition, preoperative placement of a ventriculoperitoneal shunt will treat hydrocephalus, but may limit the surgical options for tumor exposure. The differential diagnosis for this solid anterior third ventricular mass is presented, and the method of treatment for this case is discussed. PMID- 1407463 TI - Suprasellar granular cell tumor. AB - A case of a suprasellar granular cell tumor, approximately 1.5 cm in diameter, in a 68-year-old woman is described. Diagnosis was established postoperatively by histopathological examination of the tumor tissue. The preoperative computed tomographic scan revealed a slightly hyperdense suprasellar mass with strong contrast enhancement. There was no evidence of calcification. The T1-weighted image on magnetic resonance imaging scan showed an isointense tumor with non homogeneous enhancement after intravenous gadolinium diethylene-triamine pentaacetic acid. In the proton-weighted image, the suprasellar mass presented a non-homogeneously enhanced signal. A non-homogeneous signal reduction was seen in the T2-weighted image. PMID- 1407464 TI - Solitary eosinophilic granuloma invading the clivus of an adult: case report. AB - A 41-year-old white man with facial pain and diplopia was found to have an invasive lesion of the clivus. The final pathological diagnosis was eosinophilic granuloma. The patient's symptoms resolved completely after transsphenoidal resection of the lesion. The pathological and radiological diagnosis and the treatment of solitary eosinophilic granulomas are discussed. PMID- 1407465 TI - Spinal epidural angiolipoma: rare or unreported? AB - Three cases of spinal epidural angiolipoma, all affecting middle-aged women, are reported. Spinal epidural angiolipomas are considered a separate entity from the more common lipomas involving the same space. Although these tumors are considered very rare, the occurrence of three cases in less than 2 years in the same geographical area raises the question of their frequency. The computed tomographic scan has been misleading in two of our patients, whereas magnetic resonance imaging was highly suggestive. Two of these tumors were apparently exceptional, being lumbar and anterior. The patients were admitted with typical sciatic symptoms; one tumor eroded the vertebral body. Spinal epidural angiolipomas may go unreported because their pathogenetic potential is not fully recognized. We suggest that both magnetic resonance imaging and the operating microscope should have a more significant place in the evaluation and treatment of sciatica. PMID- 1407466 TI - "Dolichoectatic" intracranial vertebrobasilar dissecting aneurysm. AB - We report five patients with intracranial vertebrobasilar dissecting aneurysms, all of whom had ischemic symptoms. Angiographically, four of the five cases revealed distention and elongation of the vertebrobasilar artery like dolichoectasia and one irregular stenosis, the so-called "string sign". Magnetic resonance imaging disclosed all dolichoectatic dissecting lesions by demonstrating intimal flaps, double lumen, or subacute clot in the false lumen. We also present a successful demonstration of slow flow in the false lumen by gradient refocused magnetic resonance imaging scan with partial flip angle by the cardiac gating method. It is suggested that many of the classical "dolichoectasia" may include dissecting lesions. PMID- 1407467 TI - Carotid cavernous fistula and false aneurysm of the cavernous carotid artery: complications of transsphenoidal surgery. AB - Injury to the cavernous internal carotid artery is an unusual and serious complication of transsphenoidal surgery. Two such patients with injury to the carotid artery, referred for endovascular treatment, are reported. The clinical course and successful treatment of these patients, one with an intracavernous false aneurysm and one with a carotid cavernous fistula, are described. A review of these vascular complications of transsphenoidal surgery is presented. PMID- 1407468 TI - Cerebral arteriovenous malformations in a pregnancy with twins: case report. AB - The natural course of cerebral arteriovenous malformations during pregnancy is not well known. An inoperable cerebral arteriovenous malformation was diagnosed by angiography, computed tomography, and magnetic resonance imaging before pregnancy and followed by magnetic resonance imaging during pregnancy. No significant changes were detected in the size of the cerebral arteriovenous malformation during pregnancy, and healthy twins were born by cesarean section. PMID- 1407469 TI - Acute bilateral ophthalmoplegia secondary to cavernous sinus metastasis: a case report. AB - A case of a 60-year-old man with metastatic adenocarcinoma of the colon who developed bilateral ophthalmoplegia acutely is presented. Bilateral cavernous sinus metastasis was suggested by magnetic resonance imaging and proven by endoscopic sphenoidal biopsy. The patient was treated with radiotherapy (2000 cGy) with near resolution of his symptoms. This patient represents the first reported case of acute bilateral ophthalmoplegia resulting from hematogenous metastasis to both cavernous sinuses, diagnosed antemortem. A review of the more common causes of acute bilateral ophthalmoplegia is presented. PMID- 1407470 TI - Bilateral homonymous hemianopsia due to tentorial herniation, with sparing of central vision: case report. AB - Cases of complete bilateral homonymous hemianopsia with sparing of central vision that are caused by bilateral tentorial herniation are extremely rare. We describe one such case resulting from severe head trauma, the first to be reported in which magnetic resonance images showed clear evidence of the responsible lesion. The causes of bilateral homonymous hemianopsia with sparing of central vision and the possible mechanisms whereby macular sparing may arise are discussed. PMID- 1407471 TI - Positron emission tomography-guided stereotactic brain biopsy. AB - We describe a technique that allows target definition for stereotactic brain biopsy using coordinates calculated on stereotactic positron emission tomographic (PET) images. In this study, PET images were obtained using [18F]-labeled fluorodeoxyglucose, a marker for glucose metabolism. The difference between PET calculated and actual stereotactic coordinates of simulated targets is within PET spatial resolution. Combined computed tomography- and PET-guided stereotactic biopsies were performed in 11 patients with brain tumors. In this report, we describe two representative patients who underwent stereotactic brain biopsy using the present technique. Because of the complementary role of PET and computed tomography, their integration in multimodality planning might optimize the target selection for stereotactic brain biopsies. PMID- 1407472 TI - Ultrasonographic and electrophysiological adjuncts to surgery within the brain stem: technical note. AB - The surgical approach to intrinsic lesions within the brain stem is undertaken by the surgeon knowing the potential for significant operative morbidity. We report the use of real-time intraoperative ultrasound and electrophysiological mapping techniques to aid in the localization and resection of an intrinsic brain-stem tumor in a child. These techniques permitted an aggressive surgical approach without encountering adverse postoperative neurological sequelae. PMID- 1407473 TI - Intradural extramedullary cavernous angioma: case report. PMID- 1407474 TI - Neurological features of cranial vault lymphomas: report of two cases. PMID- 1407475 TI - Preoperative diagnosis of an extradural cyst arising from a spinal facet joint: case report. PMID- 1407476 TI - Prophylactic hypervolemia without calcium channel blockers in early aneurysm surgery. PMID- 1407478 TI - Electroconvulsive therapy-induced cortisol release after dexamethasone in depression. AB - ECT-induced cortisol release was distinctly seen, and fell along a course of ECT in each of 12 inpatient male melancholics (p = 0.00024, binomial), with dexamethasone given to diminish the elevated baseline cortisol levels typically seen in depression. Cortisol release dropped on average by 55% (p = 0.015), from 16.6 +/- 6.8 micrograms/dl (p = 0.000002) with the first ECT to 8.0 +/- 7.7 micrograms/dl (p = 0.000003) after 6 or more ECTs. The fall along the course was larger with unilateral ECT than bilateral ECT (p = 0.042), although significant regardless of electrode placement, suggesting that unilateral ECT tends to lose therapeutic impact along a course in comparison to bilateral ECT. PMID- 1407477 TI - Effect of plasma from premenstrual syndrome and control patients on human platelet and rat brain synaptosome monoamine oxidase B activity. AB - The present study determined the kinetic properties of platelet monoamine oxidase (MAO) in patients with premenstrual syndrome (PMS) and control subjects during the pre- and postmenstrual intervals. In addition, we investigated the effects of plasma obtained during the pre- and postmenstrual intervals from both subject groups on MAO activity in washed human platelets and rat brain synaptosomes. The Vmax of platelet MAO in postmenstrual PMS patients was significantly less than that during the premenstrual phase. Plasma from both subject groups (10-100 microliters) inhibited platelet and synaptosomal MAO in a dose-dependent manner to approximately the same degree at each time interval. The results indicate that although human plasma contains endogenous substances which inhibit MAO activity, alterations in their concentration are probably not responsible for the previously reported transient changes in platelet MAO activity in PMS. PMID- 1407479 TI - Residual effects of repeated administration of triazolam and nitrazepam in healthy volunteers. AB - The residual effects of hypnotics were investigated with a long-acting (nitrazepam) and a short-acting (triazolam) benzodiazepine hypnotic in 8 male volunteers. Subjects received placebo, nitrazepam 5 mg, or triazolam 0.25 mg for 7 consecutive nights in a random-order, double-blind crossover design. Daytime sleepiness, psychomotor performance, EEG activity and standing steadiness were assessed in the morning after 1, 4, and 7 days of drug treatment. Plasma concentrations of nitrazepam and triazolam were also assayed. The concentration of nitrazepam increased gradually during the course of treatment and was associated with residual sedative effects on days 4 and 7. Nitrazepam produced no apparent psychomotor impairments in these studies. On the other hand, there was no evidence of drug accumulation after triazolam administration and triazolam showed no residual sedative effects or residual impairment of psychomotor performance during the experiment. Thus, short-acting hypnotics may have an advantage over long-acting hypnotics in terms of producing less residual sedative effects during chronic treatment. PMID- 1407480 TI - Clinical safety and efficacy of tianeptine in 1,858 depressed patients treated in general practice. AB - 1,927 outpatients were included by 392 general practitioners in an open study in order to evaluate the safety of tianeptine in the ambulatory treatment of depression. The results of 1,858 depressed patients without melancholia and psychotic features, fulfilling DSM III criteria of Major Depressive Episode or Dysthymic Disorder, could be analysed. 1,458 patients completed the 3-month treatment period. The group treated with 37.5 mg/day of tianeptine showed improvement on the Montgomery-Asberg Depression Rating Scale. With regard to the clinical tolerance of tianeptine, somatic complaints were rarely reported and adverse events necessitating premature termination of treatment (4.8% of included patients) were without clinical severity. Cardiovascular, haematologic, hepatic and biochemical safety were verified. No signs of dependence and no specific withdrawal symptoms were found after discontinuation of treatment. PMID- 1407481 TI - Selective effects of colds and influenza on human performance efficiency: a critical appraisal. AB - This paper provides an appraisal of the results published from the MRC Common Cold Unit on human performance efficiency during minor upper respiratory tract infection, i.e., colds and influenza. Despite strict controls employed in the methods of data collection, the robustness of the results and some of the conclusions drawn are questioned. In particular, the claim that colds and influenza lead to selective (and different) effects is criticised as being based on incomplete data. The lack of replication, the small sample sizes, possible response biases and use of controls are considered. Overall, it is argued that there are insufficient data to provide conclusive evidence for selective effects and that over-generalisation from such studies can be misleading. PMID- 1407483 TI - Effects of age on event-related potentials in chronic alcoholics: a multimodal study. AB - To test different versions of the premature aging hypothesis in alcoholics, brainstem auditory evoked potentials (BAEPs), long-latency auditory evoked potentials (LAEPs), P3 and visual evoked potentials (VEPs) were recorded in 32 alcoholic subjects. The phenomena in patients' event-related potentials (ERPs) differ from those observed in normal aging subjects and become more pronounced with age. ANOVA showed a significant effect by group (alcoholic patients/controls) on certain parameters of BAEPs (III, III-V, I-V), VEPs (P100 latency) and LAEPs (N1-P2 amplitude and N2 latency) unaffected by age, while age had a significant effect on some parameters of LAEPs (N2-P3 amplitude, P3 latency) unaffected, or less affected by chronic alcohol consumption. At a clinical level, abnormalities in BAEPs and VEPs seem good early trouble indices in alcoholic patients, while alterations in latencies and amplitudes of LAEPs appear in older patients. These data seem to be in favor of a critical age or critical abuse in the action of alcohol, in place of the classical hypothesis of premature aging. PMID- 1407482 TI - Cognitive and psychomotor function during severe insulin-induced hypoglycaemia in insulin-dependent diabetic patients. AB - Cognitive and psychomotor function, hormonal counterregulation and symptom awareness during severe insulin-induced hypoglycaemia were evaluated in 10 insulin-dependent diabetic patients. The glucose-clamp technique (Biostator) was applied to achieve a stable hypoglycaemic (39 +/- 2 mg/dl) plateau. A battery of 7 neuropsychological tests and a standardized questionnaire assessing hypoglycaemia symptoms were administered during euglycaemia and hypoglycaemia. There was a significant increase in counterregulatory hormone response (cortisol, growth hormone, p less than 0.05). Every patient experienced symptoms during severe hypoglycaemia. Four patients, however, were not aware of this threatening metabolic state. There was a significant performance decrement in all but two neuropsychological tests (Aiming Center I, Aiming Center II, Line Tracing Errors, Reaction Time, p less than 0.01; Digit Symbol, p less than 0.05). Performance of simple motor tasks as well as cognitive tasks requiring complex discrimination deteriorated similarly. Furthermore, the patients' general well-being (subjective condition) worsened considerably. In conclusion, a significant impairment of neuropsychological functions emerged during severe hypoglycaemia in insulin dependent diabetes mellitus, even in the face of adequate hormonal counterregulation, and did not always coincide with an appropriate patient awareness of the actual metabolic state. PMID- 1407484 TI - Strange attractors, chaotic behavior and informational aspects of sleep EEG data. AB - In order to perform a nonlinear dimensional analysis of the sleep EEG, we applied an algorithm proposed to calculate the correlation dimension D2 of different sleep stages. D2 characterizes the dynamics of the sleep EEG, estimates the degrees of freedom, and describes the complexity of the signal under study. An attempt is made to correlate dimensionality analysis and informational aspects of the sleep EEG. Information processing by the brain during different sleep stages of healthy subjects under the influence of lorazepam and in unmedicated acute schizophrenics is estimated. PMID- 1407485 TI - Componential analysis of problem-solving ability: performance of patients with frontal lobe damage and amnesic patients on a new sorting test. AB - A new sorting task designed to isolate and measure specific components of problem solving ability was administered to four subject groups: patients with focal frontal lobe lesions, patients with both frontal dysfunction and amnesia (Korsakoff's syndrome), patients with circumscribed (non-Korsakoff) amnesia, and normal control subjects. The patients with circumscribed (non-Korsakoff) amnesia, and normal control subjects. The patients with frontal lobe lesions and patients with Korsakoff's syndrome were impaired on eight of the nine components of the task. The findings run counter to theories of a single or primary impairment in patients with frontal lobe dysfunction. Rather, the results suggest that a wide spectrum of deficits in abstract thinking, cognitive flexibility, and use of knowledge to regulate behavior contributes to the problem-solving impairment of these patients. Although the (non-Korsakoff) amnesic patients performed similarly to normal subjects on most measures, a finer analysis suggested that successful performance on this complex sorting task, in addition to being strongly dependent upon frontal lobe function, is mildly dependent upon memory function. PMID- 1407486 TI - Letter matching in the hemispheres: speed-accuracy trade-offs. AB - Eight subjects performed physical and nominal letter-matching tasks for pairs of letters presented in the left, right, or central visual fields, using a unimanual two-choice response-time paradigm. Latencies were manipulated by using a cued response procedure, and speed-sensitivity and speed-bias functions were calculated separately for each of the peripheral visual field by response hand conditions. Hemispheric contributions to these tasks were investigated by looking for evidence of exclusive specialization and callosal transfer. The results suggest that both hemispheres are able to perform the tasks and that they do so using similar processing strategies, but they differ in the response-choice stage of the nominal identity task. PMID- 1407488 TI - Revisiting the oddball paradigm. Non-target vs neutral stimuli and the evaluation of ERP attentional effects. AB - We recorded topographic mapping of auditory evoked potentials (AEPs) to homogeneous series of tones delivered in the absence of any cognitive task ("neutral condition") and compared them with responses to identical stimuli when they acted as non-targets in an oddball paradigm. With respect to the neutral condition, non-target responses showed an increase in N100 amplitude which was found to depend on two different, but partially overlapping effects. The "early effect" had similar latency and topography as exogenous N100 and may reflect changes in the overall state of alertness since its amplitude declined at the end of the test. The "late effect" affected the N100s descending slope and had features consistent with those of a processing negativity. It was frontally distributed, and topographic mapping revealed a right-sided predominance. Finally, non-target responses exhibited a central positivity (P250) which did not appear in neutral AEPs. P250 shares several features, including latency, amplitude and scalp topography, with the endogenous ERP component commonly labelled "P3a". Non-target P250 could be the result of an attentional shift towards the stimuli, and reflect some aspects of the classification process. We suggest that non-target responses in simple oddball paradigms should be routinely studied along with target responses in order to improve the diagnostic capabilities of cognitive ERPs. Notably, non-target responses may help to decide whether an abnormal target-P300 is related or not to a deficit in the mobilization of attentional resources. PMID- 1407487 TI - Troubled reaching after right occipito-temporal damage. AB - We encountered a man with an unusual reaching disturbance due to a stroke in the right occipito-temporal cortex and subjacent white matter. We studied his behavior in detail including vision and hand control. He had a left homonymous hemianopia. In his remaining fields static visual acuity and stereoacuity were normal, but he could not detect a coherent motion signal or follow moving targets with smooth pursuit. Transduction of limb movements using an optoelectronic technique showed abnormal morphology, increased variability and markedly prolonged latencies for transport to external visual targets, yet he achieved these targets with precision. Reaching to self-bound targets, and to the remembered locations of external targets with vision blocked was 5 x faster. The findings may be explained by: (1) damage in regions homologous to areas TF and TH in the monkey, which provide visual inputs to hand and forelimb representations in the cortex; (2) injury in human regions homologous to the monkey's MT complex, with inability to use visual information on the movement of the limb due to a visual motion processing defect; and (3) disruption of visual cortical subcortical connections mediating crucial transformations among limb and target representations. PMID- 1407489 TI - Orienting of auditory spatial attention: effects of a lateralized tone cue. AB - Mondor and Bryden [8] (Neuropsychologia 29, 1179-1190, 1991) reported that the normal Right Ear Advantage for the identification of verbal material presented dichotically could be largely eliminated if subjects were cued to attend to and report from only one ear on each trial. In these experiments, the ear to be attended was cued by presentation of a tone to that ear only prior to each dichotic trial. The present series of studies were undertaken to determine whether this lateralized tone cue exerted its effect by orienting attention or by alerting the subject of the forthcoming trial. Results revealed that for both the right and left ears the facilitating effect of the cue was dependent on the accuracy of the location information it conveyed. Thus, the precueing technique originally employed by Mondor and Bryden as a means of controlling the contribution of attention to ear advantages was validated. It is concluded that the precueing technique provides a powerful means for specification of the extent to which attentional factors and hemispheric functional capabilities contribute to ear asymmetries. PMID- 1407490 TI - Direction of lateral eye movements as an index of cognitive mode and emotion: a reappraisal. AB - Three experiments were designed to determine the effects of cognitive and emotional questions on subjective ratings, lateral eye movement (LEM) incidence and LEM direction. Although the cognitive content of questions affected subjective ratings and the incidence of LEMs, emotional content had an effect only on subjective ratings. Neither cognitive nor emotional content influenced LEM direction. The results raise doubts about the sensitivity of LEM direction as an index of lateralized cerebral processing. PMID- 1407491 TI - Right hemisphere advantage for social recognition in the chick. AB - Recognition of familiar and unfamiliar conspecifics was studied in pair-reared chicks tested binocularly or with only one eye in use. Chicks were tested on day 3 in pairs composed of either cagemates or strangers. Social discrimination, as measured by the ratio "number of pecks at the strangers/total number of pecks" was impaired in right-eyed chicks with respect to left-eyed and binocular chicks. Male chicks showed higher levels of social pecking than females, and chicks that used both eyes showed higher pecking than monocular chicks. There were no significant differences in the total number of pecks (i.e. pecks at companions plus pecks at strangers) between right- and left-eyed chicks: the impairment in social discrimination of right-eyed chicks seemed to be due partly to a reduction in pecking at strangers and partly to an increase in pecking at companions. It is suggested that neural structures fed by the left eye (mainly located at the right hemisphere) are better at processing and/or storing of visual information which allows recognition of individual conspecifics. This may be part of a wider tendency to respond to small changes in any of a variety of intrinsic stimulus properties. PMID- 1407492 TI - A comparison of normal old rats and young adult rats with lesions to the hippocampus or prefrontal cortex on a test of matching-to-sample. AB - Rats with lesions to the dorsal hippocampus (HPC) or prefrontal cortex (PFC), normal old rats, and young adult controls were compared on a test of matching-to sample. Subjects were presented with two lights in succession and were trained to press a lever when the lights were the same brightness and withhold a lever-press when they were different. The PFC and aged groups, but not the HPC group, were impaired when the comparison stimulus was presented immediately after the sample stimulus. When delays of 5 and 15 sec were introduced between the stimuli, the HPC and aged groups' performance deteriorated to chance levels. The PFC group's performance was not differentially affected by the delays. The results were consistent with previous findings that implicated the HPC in episodic memory and the PFC in working memory. The aged group was impaired on both types of memory, revealing signs of HPC and PFC dysfunction. PMID- 1407493 TI - Perception of optical flow in cortical blindness: a case report. AB - Motion perception was studied in a subject with bilateral lesion of the visual cortex, involving severe damage to cortical areas V1 and V4, but with no apparent damage to visual associative areas situated in occipito-parietal and lateral occipito-temporal (presumably V5) zones. He was able to perceive optical flow motions simulating motion in depth in "blind" parts of his visual field, provided that the stimulus-onset was temporally dissociated from its motion. Moreover, he was able to discriminate between different velocities and directions of motion. The results suggest that perimetrically "blind" parts of the visual field in this patient have true capacities to process visual motion. They are discussed in reference to the subject's ability to move freely in his environment and in reference to the role of extrastriate visual pathways in visual motion processing. PMID- 1407494 TI - Pseudoneglect and reversed pseudoneglect among left-handers and right-handers. AB - Two experiments were carried out to examine specific hand contribution to pseudoneglect and reversed pseudoneglect phenomena in dextrals and sinistrals when bisection tasks were conducted exclusively in the midline spatial condition. Both dextrals and sinistrals showed the same overall pattern deviation: in the tactile scanning task, both right and left hands deviated to the left of the midpoint and in the kinesthetic scanning tasks, the right hand deviated to the left and the left hand to the right of the midpoint. However, when these deviations were tested against zero (i.e. the objective midpoint) clear differences appeared related to hand, task and handedness. These results were discussed with respect to "enhancement theory". PMID- 1407495 TI - Cognitive flexibility and mental programming after closed head injuries and anterior or posterior cerebral excisions. AB - Cognitive inflexibility and deficient mental programming are specifically related to frontal lobe lesions. The aim was to demonstrate that closed head injury (CHI) patients with brain lesions verified by computed tomography have such cognitive deficits, and are inferior in these respects to patients with posterior cerebral excisions mainly for tumours. This hypothesis was confirmed using a Category Identification and Sorting test as well as a measure of mental programming in a Spatial Learning task. Furthermore, CHI patients who had non-frontal parenchymal lesions were inferior by these measures to patients with posterior excisions. This result suggests that diffuse axonal lesion in CHI causes the deficits similar to those following frontal lobe excision. PMID- 1407496 TI - Learning and retention of melodic and verbal information after unilateral temporal lobectomy. AB - The role of the temporal lobes in auditory memory was tested in two analogous tasks assessing learning and 24-hr delayed recognition of unfamiliar melodies and nonsense words. The performance of patients with either anterior right (RT) or left (LT) temporal lobectomy was impaired in learning and delayed recognition of both melodies and words, as compared to normal control subjects, although some preserved learning over successive trials was observed. These results suggest a bilateral temporal-lobe contribution to the learning of these auditory patterns. However, melodies and nonsense words were not recognized in the same way by the two patient groups after 24 hr: subjects in the LT group tended to improve on melodies but drop on words, whereas subjects with RT lesions displayed the reverse pattern, suggesting a differential role for each temporal lobe in long term memory, according to the nature of the cues inherent to a given type of stimulus. PMID- 1407497 TI - Right hemisphere specialization for the identification of emotional words and sentences: evidence from stroke patients. AB - This study examines the contribution of the lexical/verbal channel to emotional processing in 16 right brain-damaged (RBD), 16 left brain-damaged (LBD) and 16 normal control (NC) right-handed adults. Emotional lexical perception tasks were developed; analogous nonemotional tasks were created to control for cognitive and linguistic factors. The three subject groups were matched for gender, age and education. The brain-damaged groups were similar with respect to cerebrovascular etiology, months post-onset, sensory-motor status and lesion location. Parallel emotional and nonemotional tasks included word identification, sentence identification and word discrimination. For both word tasks, RBDs were significantly more impaired than LBDs and NCs in the emotional condition. For all three tasks, RBDs showed a significantly greater performance discrepancy between emotional and nonemotional conditions than did LBDs or NCs. Results were not affected by the valence (i.e. positive/negative) of the stimuli. These findings suggest a dominant role for the right hemisphere in the perception of lexically based emotional stimuli. PMID- 1407498 TI - Opposite hemispheric activations as a result of emotionally threatening and non threatening words. AB - Twenty right-handed males participated in a tachistoscopic unilateral letter recognition task with three conditions. In the control condition, each trial consisted of three consonants that were flashed horizontally to the left or to the right visual field. In the threat and non-threat conditions, each lateral three-letter presentation was preceded by an emotionally threatening or non threatening word presented in central fixation. Across conditions, subjects identified more letters correctly in the right visual field than in the left visual field. The concurrent presentation of threatening words resulted in a selective enhancement of left visual-field performances. The concurrent presentation of non-threatening words resulted in a selective right visual-field enhancement. Our conclusion is that threatening stimuli prime the right hemisphere and can alter predicted laterality patterns. PMID- 1407499 TI - Role of the lateral and medial hypothalamus in the reproduction of alimentary and defensive instrumental reactions. AB - It was established in experiments on two dogs that a test electrical stimulation of the lateral hypothalamus reproduces an instrumental movement in the case of a developed alimentary instrumental CR to a tone and does not reproduce it in the case of a developed acid defensive instrumental CR. In the case of an electrical stimulation of the medial hypothalamus, the instrumental movement is essentially not reproduced, either in the alimentary or the defensive situations. The appearance of the instrumental movement with electro-stimulation of the LH in the alimentary situation is associated with activation of the backward conditioned connection from the motivational "alimentary" center of the LH to the representation of this movement in the motor cortex. PMID- 1407500 TI - Statistical analysis of the functional connections between the neurons of the visual and motor cortex in different forms of conditioned reflex behavior. AB - The organization of interneuronal cortical connections was studied in experiments on cats with the development of delayed alimentary instrumental reflexes in response to light. The dynamics of the intra- and interstructural neuronal network at the level of the cortical projection (visual and motor) zones of the cat brain in three forms of behavior was revealed through a cross correlation analysis: the realization of the CR, in the intersignal period with the presence and absence of instrumental movements. The predominance of "informational" or "motivational" neuronal connections was observed depending upon the forms of the behavior. PMID- 1407501 TI - Content of norepinephrine and serotonin in symmetrical divisions of the brain of rats in the norm during learning and with the administration of peptides. AB - The content of norepinephrine (NE) and serotonin (5-HT) in the right and left halves of the brain of rats was compared in the norm, during the development of defensive two-way avoidance conditioned reflexes (TWACR), and with the administration of peptides which influence learning and memory, namely desglycine arginine vasopressin (DG-AVP), ACTH4-7 pro-gly-pro, and dalargin. These investigations demonstrated that the content of NE in the right cerebral hemisphere is significantly higher than in the cortex of the left. Significant differences were not detected with respect to the 5-HT content in symmetrical parts of the brain. The asymmetry of the NE content was eliminated under the influence of the development of the TWACR. The systemic administration of DG-AVP, ACTH4-7 pro-gly-pro, and dalargin essentially did not alter the 5-HT content, and decreased the NE content in the cortex and in the rest of the brain. In the process the NE content of the right and left hemisphere evened out. The data obtained point to the asymmetrical character of the action of the neuropeptides and to the greater resistance of the serotoninergic system of the brain to a functional load and the administration of peptides by comparison with the noradrenergic system. PMID- 1407502 TI - Development of auditory sensitivity of altricial birds: absolute thresholds of the generation of evoked potentials. AB - The thresholds of the generation of EP in the L field of two to nine day old pied flycatcher nestlings in response to monotonal bursts of varied frequency were investigated. The entire range of auditory sensitivity was divided into three channels on the basis of the character of the age-related dynamics of the thresholds (two to nine days of life): low-frequency (0.3-1.6 kHz), middle- (1.5 4.0 kHz), and high-frequency (5.0-8.0 kHz). Widening of the auditory range in the direction of high frequencies on the 4th to 5th days of nest life was demonstrated. It was shown that the development of auditory sensitivity continues in all three channels in the post-embryonic period (two to nine days after hatching), and that each of these is characterized by its own thresholds time course. PMID- 1407503 TI - Reinforcing effect of stimulation of the mesocerebral region of the brain of the edible snail. AB - Two regions of the brain of the edible snail were stimulated. The spontaneous movements, either opening or closing, of the opening of the mantle cavity served as the signal for the stimulation. The stimulation of the region of the mesocerebrum of the edible snail in a semi-intact preparation may serve as a positive reinforcement of intercurrent behavior, while stimulation of the rostral portion of the parietal ganglia may serve as a negative reinforcement. Depending upon whether the movement itself or its absence is reinforced, the change in the intercurrent behavior may change sign. PMID- 1407504 TI - Impulse activity of neurons of the parietal associative cortex in conditioned instrumental food-procuring behavior of cats. PMID- 1407505 TI - Dynamic reorganization of the central program of precision instrumental movements in cats. PMID- 1407506 TI - Reactions of neurons of the mediodorsal nucleus of the thalamus to the stimulation of peripheral nerves. AB - The reactions of neurons of the associative mediodorsal nucleus of the thalamus to a solitary stimulation of the radial, sciatic, and splanchnic nerves were studied in conditions of an acute experiment in anesthetized and immobilized cats. There were 91.85, 90.56, and 81.35% reactive neurons, respectively. They were mainly concentrated in the parvocellular division of the nucleus. A high degree of convergence (82.6%) of somatic and visceral signals was found and their interaction was of the reciprocal blocking type. PMID- 1407507 TI - Changes associated with the organization of motor acts in the on-going frequency of the discharges of neurons of subcortical structures of the human brain. AB - The impulse activity of subcortical structures was recorded in 16 parkinsonian patients (six women) using deep electrodes implanted in the strio-pallido thalamic system on the basis of treatment and diagnostic indications. The patients voluntarily participated in four psychological tests. Two groups of pallidal and thalamic neuronal populations (neuronal populations associated with the response and associated with the stimulus, containing 25% each out of the total number of neuronal populations recorded) were classified on the basis of evoked changes in on-going frequency in the motoric version of the odd ball test. Some of the neuronal populations associated with the response reacted primarily during counting, some during the naming of the stimulus, and some during button pressing. PMID- 1407508 TI - Descending neuronal projections to the lumbar division of the cat spinal cord. PMID- 1407509 TI - Perception and experience of time by patients with depression in manic-depressive psychosis and attack-like schizophrenia. PMID- 1407510 TI - Modules of cortical neurons and their "self-assembly". AB - The data we have by now accumulated on the cytoarchitectonics of the cerebral cortex, as well as published data, suggest that some of the neurons are structurally combined into compact clusters (ensembles, blocks), and that the majority of them participate in the construction of these clusters by directing the terminal branches of their axons to them. The collaterals of projection, associative, and callosal nerve cells, as well as the axons of interneurons which accomplish local interneuronal closures, can combine individual elements of the ensembles into a unified morphofunctional system. The collaterals of the axons of a block of neurons spread divergently to neurons disposed along the perimeter, while the axons of the latter converge reciprocally to the neurons of the cluster, forming a maximum (focus) of the arborization of the axonal terminals there; this makes it possible actively to isolate modules of nerve cells by accomplishing their self-assembly. PMID- 1407511 TI - Conditioned avoidance reflex and intersignal movements: interrelationship of cardiac and motor components. AB - The correlation of the heart rate (HR), of a conditioned motoric reaction, and intersignal movements was studied during the development of a conditioned reflex (CR) of avoidance using V.P. Petropavlovskii's methods. The level of defensive motivation, assessed on the basis of the magnitude of changes in HR was maximal against the background of a firmly developed CR during the course of the latent period of the conditioned motoric reaction. A sharp decrease in the level of defensive excitation took place against the background of the latter, expressed in the prolonged holding of the extremity in place in the safety zone (height of rise 5-10 cm, guaranteeing the avoidance of electrodermal stimulation of the extremity). Intersignal movements of two types were described: the first in the form of phasic flexions; the second repeats the conditioned motoric reaction of the holding of the extremity in place. A reduction in defensive excitation took place against the background of the latter, like that which took place during the elevation of the extremity against the background of the combination. PMID- 1407512 TI - Infratemporal alveolar soft part sarcoma: CT, MRI and angiographic findings. AB - The imaging features of a rare alveolar soft part sarcoma found in a 44-year-old female are presented. Although the tumor showed hypervascularity by angiography, CT and MRI suggested slow growth. Despite this relatively benign appearance, alveolar soft part sarcoma is one of the most malignant sarcomas. PMID- 1407514 TI - Intraparenchymal blood-fluid levels in traumatic intracerebral haematomas. AB - Blood-fluid levels within the cerebral parenchyma are observed more frequently on CT and MRI in traumatic intracerebral haematomas than in those of other aetiologies. The intraparenchymal blood-fluid interface can be formed without a fluid cavity. It is suggested that the blood-fluid levels represent layering of red blood cells within areas of contusion necrosis as well as extensive contusion oedema. The more extensive the damage to brain tissue, the more often blood-fluid levels formed. A poorer outcome can be therefore predicted when an intraparenchymal blood-fluid interface is seen. PMID- 1407513 TI - Pulsatile brain movement and associated hydrodynamics studied by magnetic resonance phase imaging. The Monro-Kellie doctrine revisited. AB - Brain tissue movements were studied in axial, sagittal and coronal planes in 15 healthy volunteers, using a gated spin echo MRI sequence. All movements had characteristics different from those of perfusion and diffusion. The highest velocities occurred during systole in the basal ganglia (maximum 1.0 mm/s) and brain stem (maximum 1.5 mm/s). The movements were directed caudally, medially and posteriorly in the basal ganglia, and caudally-anteriorly in the pons. Caudad and anterior motion increased towards the foramen magnum and towards the midline. The resultant movement occurred in a funnel-shaped fashion as if the brain were pulled by the spinal cord. This may be explained by venting of brain and cerebrospinal fluid (CSF) through the tentorial notch and foramen magnum. The intracranial volume is assumed to be always constant by the Monro-Kellie doctrine. The intracranial dynamics can be viewed as an interplay between the spatial requirements of four main components: arterial blood, capillary blood (brain volume), venous blood and CSF. These components could be characterized, and the expansion of the arteries and the brain differentiated, by applying the Monro-Kellie doctrine to every moment of the cardiac cycle. The arterial expansion causes a re-moulding of the brain that enables its piston-like action. The arterial expansion creates the prerequisites for the expansion of the brain by venting CSF to the spinal canal. The expansion of the brain is, in turn, responsible for compression of the ventricular system and hence for the intraventricular flow of CSF. PMID- 1407515 TI - Corpus callosum lesions after closed head injury in children: MRI, clinical features and outcome. AB - Thirty-four children who sustained moderate to severe closed head injury underwent magnetic resonance imaging (MRI). Eight (24%) had MRI evidence of corpus callosum injury, most commonly within the posterior body and splenium. In contradistinction to reports in adults, there was no definite relationship between callosal injury and lower initial Glasgow Coma Scale scores, nor was there a significantly higher incidence of primary brain-stem lesions, diffuse axonal shear injury or intraventricular hemorrhage. In none of these 8 children did the initial admission computed tomography show evidence of callosal injury. Callosal injuries on MRI are not necessarily a poor prognostic finding, the majority of the 8 children showing good functional recovery. PMID- 1407516 TI - MRI and SPECT findings in amyotrophic lateral sclerosis. Demonstration of upper motor neurone involvement by clinical neuroimaging. AB - MRI was performed in 21 patients and single photon emission computed tomography (SPECT) with N-isopropyl-p-123I iodoamphetamine in 16 patients, to visualize upper motor neurone lesions in amyotrophic lateral sclerosis. T2-weighted MRI revealed high signal along the course of the pyramidal tract in the internal capsule and cerebral peduncle in 4 of 21 patients. SPECT images were normal in 4 patients, but uptake was reduced in the cerebral cortex that includes the motor area in 11. PMID- 1407517 TI - MRI in the early stage of Tay-Sachs disease. PMID- 1407519 TI - MRI demonstration of midbrain deformity in association with Chiari malformation. AB - The differentiation of Chiari malformation from intrinsic brainstem neoplasm in adults can be difficult. We report three patients presenting with brainstem signs, in whom midbrain abnormality was detected on computed tomography and interpreted as evidence of intrinsic tumour. Subsequent investigation by magnetic resonance imaging revealed evidence of Chiari I malformation in all three cases and a syrinx in two. The association of Chiari I with deformity of the midbrain or pons has not been described previously. PMID- 1407518 TI - Serial MRI in Fukuyama type congenital muscular dystrophy. AB - Serial MRI of the brain of a female infant with Fukuyama type congenital muscular dystrophy (FCMD) is presented. Initial MRI revealed diffuse abnormal signal in the cerebral white matter extending peripherally. On follow-up studies, the abnormal signals disappeared or decreased from the posterior to anterior, and from central to peripheral. These changes in signal intensity correlate well with the process of myelination as demonstrated in histochemical studies. It appears that the abnormal signals in FCMD are caused by delayed myelination. When abnormal signal intensity is seen in the cerebral white matter of a developmentally delayed infant, serial MRI may be used to follow the course of the illness. PMID- 1407520 TI - Pericallosal lipoma extending through the choroidal fissure: US/CT/MRI correlation. AB - Choroid plexus lipomas (CPL) are known to be associated with pericallosal lipomas (lipomas of the corpus callosum--LCC). Twenty-six cases have previously been reported. Approximately half of these lipomas are connected via the choroidal fissure (LCC-CPL); this connection is almost always bilateral. We present an unusual unilaterally connected LCC-CPL in a neonate. PMID- 1407521 TI - Supracerebellar arachnoid cyst and reversible tonsillar herniation: magnetic resonance imaging and pathophysiological considerations. AB - A large supracerebellar arachnoid cyst was associated with herniation of the cerebellar tonsils and deformity of the cervicomedullary junction in an adult. Magnetic resonance imaging showed partial restoration of normal anatomy following surgery and clinical improvement, which helped in the formulation of a etiopathogenetic hypotheses. PMID- 1407522 TI - Superficial siderosis of the brain following unexplained subarachnoid hemorrhage: MRI diagnosis and clinical significance. PMID- 1407523 TI - Lymphomatous meningitis: neuroradiological appearances. PMID- 1407524 TI - Magnetic resonance imaging and angiography in hemifacial spasm. AB - We used magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) to investigate 14 patients with unilateral hemifacial spasm (HS) and 20 controls. The relationship of the seventh and eighth cranial nerves to adjacent vessels was best visualized on the contiguous flow sensitive 3D-FISP images. Reconstruction of projectional MRA was helpful to assess the complex architecture of the vertebrobasilar system. Neurovascular contact in the facial nerve root exit zone was present in 4 of 20 controls and in 12 of 14 patients, in whom it predicted the affected side. These results support previous findings of surgical and electrophysiological investigations that local irritation of the facial nerve is the most possible explanation for HS. MRI and MRA provide vascular and brain tissue diagnosis in a single non-invasive examination and should be recommended as primary neuroradiological procedure in HS. PMID- 1407525 TI - Accessory nerve neuroma presenting as recurrent jugular foramen syndrome. AB - We report a patient with spontaneous recovery and recurrence of a jugular foramen syndrome secondary to an accessory nerve neuroma. He showed sudden onset of unilateral palsy of the ninth, tenth and eleventh cranial nerves in 1982. He recovered almost fully and in 1990 the palsies recurred. MRI revealed a small mass in the right jugular foramen. The tumour was resected via suboccipital craniectomy, and diagnosed as a neuroma of the eleventh cranial nerve. PMID- 1407526 TI - Haemangioma of the petrous bone: MRI. AB - Gd-DTPA-enhanced MRI provided accurate demonstration of the site and extension of a haemangioma of the petrous bone. Enhanced-MRI could allow early detection and differentiation from the other more common tumours of the geniculate ganglion area, thereby permitting the surgeon to remove the tumour, while preserving the facial nerve. CT is, however, required to display the characteristic ossification in these tumours. PMID- 1407527 TI - Follow-up MRI in dural arteriovenous malformations involving the cavernous sinus: emphasis on detection of venous thrombosis. AB - Six patients with a dural arteriovenous malformation (dural AVM) involving the cavernous sinus were followed up with magnetic resonance imaging in order to assess change in the lesions. Spin-echo (SE) imaging of three patients in whom the AVM appeared to have closed at least 1 month earlier (two of them spontaneously, and one after external carotid artery embolization) showed neither apparent flow void in the involved cavernous sinus nor evidence of venous thrombosis. SE images of the other three patients who had not been cured by external carotid artery embolization (two of whom were examined within a week of treatment), detected persisting arteriovenous shunts, including high-flow cortical venous drainage, seen as flow void. Two-dimensional time-of-flight MR angiography (2D TOF MRA) was performed simultaneously in three patients. Whereas shunting blood and the normal cavernous sinus were of high intensity, presumed thrombosed cavernous sinuses were isointense with stationary brain tissue. SE imaging can confirm the resolution of arteriovenous shunts, but poorly delineates very acute and chronic thrombosis of the draining veins. In contrast, 2D TOF MRA directly demonstrates flowing blood, permitting the diagnosis of venous thrombosis; it should be included in follow-up of a dural AVM involving the cavernous sinus when venous thrombosis is suspected. PMID- 1407528 TI - A scalp lesion over an extracerebral mass: a sign of a radiation-induced meningioma. AB - Radiation-induced meningiomas have a characteristic biological behaviour, so that their recognition is important as regards follow-up. We stress the importance of a scalp lesion over the meningioma on magnetic resonance imaging as a sign of previous radiotherapy. PMID- 1407529 TI - CT and MRI in hydatid disease of cervical vertebrae. AB - Hydatid disease (HD) of the cervical spine is rare. A case investigated by computed tomography (CT) and magnetic resonance imaging (MRI) is presented. While CT shows the bone lesion better, MRI is superior in demonstrating compression of neural structures. The complementary use of CT and MRI in such cases is suggested. PMID- 1407530 TI - Myelopathy due to large veins draining recurrent spontaneous caroticocavernous fistula. AB - A 45-year-old woman developed a myelopathy 9 years after a spontaneous left caroticocavernous fistula (CCF) was treated by a trapping procedure, with clipping distal to the fistula and ligation of the common carotid artery. Spinal MRI and vertebral angiography revealed recurrence of the CCF and gigantic tortuous veins draining through the brain stem down to the midcervical spinal cord. The abnormal veins and myelopathy disappeared after surgical closure of the CCF. PMID- 1407531 TI - Intraoperative sonography of intramedullary spinal cord tumours. AB - Intraoperative spinal sonography was performed 23 times in 20 patients with intramedullary spinal cord tumours, and the sonographic features were examined. Eight cases of astrocytoma were classified into three types: type 1, seen in 3 children, had intramedullary, circular or oval, hyperechogenic multiple tumour shadows; type 2 presented inter-multimyelomere, relatively well-defined single tumour shadows corresponding to grade III and I for two juvenile and aged cases each, respectively; and type 3 appeared ill-defined and diffusely infiltrating. The relationships between these types, the ages of patients and histological grades were considered a potential clue to mechanisms of occurrence and infiltration of astrocytoma. All 7 ependymomas had syrinxes, of three types; central canal was very large, the tumour lying within it like an island; or the tumour was in contact with a cephalocaudal side part of the syrinx; or the tumour had a syrinx or cyst. Sonographic images thus differ according to the tumour, but differential diagnosis is currently limited. Development of sonographic equipment, with upgrading its resolving power are hoped for. PMID- 1407532 TI - Intraoperative ultrasonography of extramedullary spinal tumours. AB - Intraoperative spinal sonography (IOSS) was performed in 28 patients with extramedullary spinal tumours. Images were obtained of 31 tumours, because 2 patients had multiple tumours. There were 17 neurilemmomas, 9 meningiomas and 2 dermoid cysts. All tumours appeared well-defined and highly echogenic. There was no difficulty differentiating extramedullary spinal tumours from intramedullary masses excepting case, a big neurilemmoma at the conus medullaris. All images were assessed with reference to the surface of the lesions, the existence of cysts, and movement. Neurilemmomas had smooth surfaces, some cysts, and exhibited a "floating" movement. Meningiomas had irregular surfaces, were more highly echogenic than neurilemmomas, and adhered tightly to the dura mater. However, some neurilemmomas and meningiomas did not have these, and it was not always possible to differentiate them. Although IOSS has limitations of resolution, it gave useful information about the size of the tumours, the degree of displacement of the spinal cord, and even about the type of tumour in some cases. It was extremely helpful to the surgeon. PMID- 1407533 TI - Myelographic and MRI appearances of a thoracic spinal extradural arachnoid cyst of the spine with extra- and intraspinal extension. AB - An unusual arachnoid cyst of the thoracic spine is reported. The clinical and neuroradiological features are described. PMID- 1407534 TI - Cystic spinal neurilemmoma on magnetic resonance imaging. AB - We report a complete cystic change of intradural neurilemmoma at the T12-L1 level. T1-weighted MRI images with gadolinium-DTPA clearly enhanced the thin capsule of the cystic tumour. PMID- 1407535 TI - Cervical neuroma associated with multiple intracranial arachnoid cysts. PMID- 1407536 TI - CT-guided chemical rhizotomy of the C1 root for occipital neuralgia. AB - Sensation in the parasagittal occipital region is usually provided by fibres from the second cervical root via the greater occipital nerve. In the case presented occipital neuralgia could be relieved only by coagulation of the C1 nerve root with 96% ethyl alcohol. Possible explanations for this observation are discussed and a technique for CT-guided treatment is described. PMID- 1407537 TI - The value of intraoperative scans during CT-guided stereotactic procedures. AB - The accuracy stereotactic procedures performed during the pre-computed tomography (CT) era was confirmed by intraoperative X-ray pictures. With the availability of CT it is now possible to confirm the position of the probe-tip on an image of the target. For biopsy of small lesions in critical areas of the brain, permanent placement of radioactive seeds, or thalamotomy, it would be desirable to have confirmation of the site of the probe-tip prior to performing the main step of the procedure. Intraoperative CT was performed in 216 stereotactic procedures carried out on the scanner table including biopsies, aspiration of cysts, brachytherapy, aspiration of abscesses, thalamotomy, and evacuation of intracerebral hematoma. In 6 cases, inaccuracies were detected, which it was possible to correct so as to place the probe where desired. PMID- 1407538 TI - Successful treatment of neonatal aneurysmal dilatation of the vein of Galen: the role of prenatal diagnosis and trans-arterial embolization. AB - We report a neonate with aneurysmal dilatation of the vein of Galen diagnosed prenatally by color Doppler sonography and MRI at 37 weeks' gestation. The child was treated by transarterial embolization of micro-coils 2 and 8 days after birth. The aneurysmal dilatation of the vein of Galen markedly decreased after embolization and the patient is developing normally at 2 years 5 months of age. Prenatal diagnosis and early intervention by transarterial embolization produced in a good outcome in this patient. PMID- 1407539 TI - Arteriovenous fistula of the internal maxillary artery in a child: case report. AB - Direct arteriovenous fistulae supplied by the external carotid artery are unusual. Rarely, congenital fistulae have been described involving the head and neck. We describe the first case of congenital internal maxillary arteriovenous fistula in a child. Balloon embolization is currently considered the method of choice for treatment of direct arteriovenous fistula. PMID- 1407541 TI - G-protein mediation in nociceptive signal transduction: an investigation into the excitatory action of bradykinin in a subpopulation of cultured rat sensory neurons. AB - Bradykinin is one of several pro-inflammatory, pain-inducing substances produced during inflammation--the body's response to injury. In previous work we have shown that bradykinin and guanosine-5'-O-3-thiotriphosphate increase excitability in a subpopulation of cultured neonatal rat dorsal root ganglion neurons. We now describe experiments in which the mechanism underlying the stimulatory action of these two substances has been examined in more detail. Using the whole-cell voltage-clamp technique, bradykinin-sensitive cells were distinguished by their response to a 1-s depolarizing voltage-pulse which evoked more than one inward current during the step command. The secondary inward currents are likely to represent action potentials generated at the poorly clamped neurites of these cells. Bradykinin- and guanosine-5'-O-3-thiotriphosphate-induced changes in excitability were measured indirectly by a change in the number of inward currents recorded during the 1-s depolarizing voltage-step. The effect of activators and inhibitors of protein kinase C, arachidonic acid metabolism, G protein activation and release of intracellular Ca2+ were examined on this response. In the presence of extracellular staurosporine (1.0 microM) or nordihydroguaiaretic acid (10 microM), these excitatory effects were reduced but not abolished, whilst indomethacin (20 microM) had no effect. Intracellular application of guanosine-5'-O-2-thiodiphosphate (10 mM) or ryanodine (100 microM) substantially reduced the effect of bradykinin. The excitatory effect of internal guanosine-5'-O-3-thiotriphosphate (500 microM) occurred gradually over time, and this was mimicked by internal application of myo-inositol 1,4,5 trisphosphorothioate (1.0 microM). From the results, it is proposed that G protein activation is an essential component of the bradykinin response, which may also require a Ca(2+)-activated conductance modulated by protein kinase C and lipoxygenase metabolites of arachidonic acid. PMID- 1407540 TI - Benzodiazepines block long-term potentiation in slices of hippocampus and piriform cortex. AB - The effects of two benzodiazepines, diazepam and triazolam, on long-term potentiation were tested in slices of hippocampus and piriform cortex. The drugs had little influence on baseline synaptic responses but both were very effective in blocking LTP elicited by theta pattern stimulation. The effects were fully reversible upon washout. Diazepam reduced the increase in burst responses that occurs during theta stimulation and thus appears to interfere with the initial triggering events for long-term potentiation. This may reflect the enhancing action of the drug on GABA-mediated inhibitory potentials. Triazolam did not detectably change the burst responses elicited by theta pattern stimulation. Experiments with slices of piriform cortex indicated that triazolam also failed to disrupt the development of long-term potentiation but instead caused the potentiation to decay back to baseline in 15-30 min. Triazolam thus seems to act on the mechanisms that stabilize long-term potentiation. These results provide a possible explanation for the amnestic effects of benzodiazepines in humans and animals and support the hypothesis that long-term potentiation contributes to memory encoding. PMID- 1407542 TI - Capsaicin differentially influences somatosensory cortical responses evoked by peripheral electrical or mechanical stimulation. AB - The effects of capsaicin injected intraperitoneally (200 micrograms/kg) or applied locally to the cortical surface (10(-5) M) were studied on cortical potentials evoked by peripheral electrical or mechanical stimulation. Capsaicin treatment (i.p.) differentially influenced the cortical evoked potentials depending on the type of stimulation. Just after both types of capsaicin application, the responses to both kinds of stimuli decreased in amplitude. Additionally, during this time a short fall in blood pressure was observed. Half an hour later, however, only in the case of interperitoneal application the potentials evoked by electrical stimulation were facilitated, while the potentials evoked by vibrissa deflection had recovered and stayed around the control levels thereafter. In addition, the responsive cortex area activated by electrical stimulation became enlarged after the i.p. injection of capsaicin, while that of the cortex region activated by mechanical stimulation did not change significantly. Capsaicin applied locally to the cortex resulted neither in the facilitation of evoked potentials nor in the enlargement of the responsive cortical area. The present findings are the first to demonstrate that the i.p. (but not local) administration of capsaicin, in low dosage, differentially influences the cortical responses evoked by electrical and mechanical stimulation of somatosensory afferents. PMID- 1407543 TI - Performance in an escape task induces fos-like immunoreactivity in a specific area of the motor cortex of the rat. AB - The expression of the c-fos proto-oncogene was studied in two different areas of the motor cortex and in the hippocampus of the rat after performance in an escape task in a Skinner box. Performance in this task caused an increase in the number of cells showing fos-like immunoreactivity in layers V and VI of the forelimb motor-sensory cortex with respect to yoked animals which had received the same amount, frequency and duration of aversive stimulation and manipulation as the trained animals. Therefore, this increase is the specific effect of performing the behavioral task. In the hindlimb motor-sensory cortex there were no differences between the trained and the yoked animals in any of the cortical layers. No differences were observed in the dentate gyrus of the hippocampus between trained and yoked animals, while the control animals showed a much lower fos-like immunoreactivity. In conclusion, infragranular layers in the forelimb representation of the primary motor cortex become activated with respect to the expression of fos-like immunoreactivity after performance in an escape task in a Skinner box. This result is consistent with the idea that even in complex structures such as the cerebral cortex, specific trace systems become activated for the performance of complex behavioral tasks. PMID- 1407544 TI - The appearance of Fos protein-like immunoreactivity in the hypothalamus of developing rats in response to cold ambient temperatures. AB - This study examined cellular activity in the hypothalamus of developing rats in response to cold environmental temperatures. The appearance of the nuclear protein, Fos, in response to cold ambient temperatures in rats three to 35 days of age was used as a marker of neuronal activation. Fos-positive nuclei were first seen in response to cold ambient temperatures in the ventromedial nucleus at three days of age, the paraventricular nucleus at eight days of age, the preoptic-anterior hypothalamus at 10 days of age and the anterior hypothalamic nucleus at 21 days of age. The rectal temperature of the 10-day-old pups dropped by less than half that measured in the nine-day-old pups after 1 h in the cold. It is possible that the activation of neurons in the preoptic-anterior hypothalamus in the 10-day-old animal may contribute to the decreased hypothermia observed in the 10-day-old after 1 h in the cold. The high density of Fos-like immunoreactive-labeled nuclei in the preoptic-anterior hypothalamus in the 10-day old rats that were exposed to the cold environment indicates increased neuronal activity at this site. The results suggest that, at least in the preoptic anterior hypothalamus, the appearance of the cellular response to cold ambient temperatures is coincidental with a thermogenic response. PMID- 1407545 TI - Increase in cytoplasmic free Ca2+ elicited by noradrenalin and serotonin in cultured local interneurons of mouse olfactory bulb. AB - Effects of noradrenalin and serotonin on cytoplasmic free Ca2+ concentrations ([Ca2+]i) were studied by using the fluorescent indicator fura-2 in cultured local interneurons of mouse olfactory bulb. Application of noradrenalin (0.1-100 microM) caused a rapid and concentration-dependent rise in [Ca2+]i, while isoproterenol was ineffective at concentrations up to 100 microM. The noradrenalin (1 microM)-induced increase in [Ca2+]i was completely inhibited by pretreatment with alpha 1-antagonist, prazosin (100 nM), whereas the inhibitory effect of alpha 2-antagonist, yohimbine, was about 100-times less potent. Serotonin (0.1-100 microM) also caused the dose-dependent rise in [Ca2+]i, which was inhibited by serotonin2 antagonist, ketanserin. Even in the absence of the extracellular calcium, the noradrenalin- or serotonin-induced increase in [Ca2+]i was observed. These results indicate that both noradrenalin and serotonin elicit the rise in [Ca2+]i in local interneurons of the olfactory bulb. They also suggest that the rise in [Ca2+]i is mediated by alpha 1-adrenergic and serotonin2 receptors, and that the increased calcium is mainly derived from intracellular calcium storage sites. The above results provide evidence to suggest that in the olfactory bulb, noradrenergic and serotonergic centrifugal fibers exert modulatory influences on synaptic interactions between mitral/tufted cells and local interneurons by increasing cytoplasmic Ca2+ in local interneurons. PMID- 1407546 TI - Membrane retrieval following exocytosis in isolated neurosecretory nerve endings. AB - In the neurosecretory nerve endings of the neurohypophysis depolarization-induced exocytosis is followed by endocytosis of vacuole-like structures with diameter similar to that of neurosecretory granules. However, it remains unknown whether the membrane of the endocytotic vacuoles is comprised primarily of retrieved secretory granule membrane, plasma membrane or of a mixture of the granule and plasma membrane. In the present paper membrane retrieval following depolarization induced exocytosis has been studied in isolated neurosecretory nerve endings from the rat neurohypophysis. The origin of the retrieved membrane was assessed by pre labeling the plasma membrane with an antibody against neural cell adhesion molecule, a plasma membrane specific protein. Horseradish peroxidase was used as an index of fluid endocytosis and secretion of vasopressin was measured by radioimmunoassay. Following potassium-induced depolarization, endocytotic vacuoles showed labeling with the fluid phase marker horseradish peroxidase but never showed significant neural cell adhesion molecule labeling. The time-course of endocytosis following closely that of exocytosis as endocytotic vacuoles labeled with horseradish peroxidase were only observed when the fluid phase marker was present in the extracellular medium during the period of evoked exocytosis. Our results are consistent with a model in which in neurosecretory nerve endings, after transient exocytotic fusion of the granule membrane with the plasma membrane, the granule membrane is rapidly and selectively retrieved into the nerve endings in the form of vacuoles similar in size to that of the neurosecretory granules. PMID- 1407547 TI - Virtual trajectories, joint stiffness, and changes in the limb natural frequency during single-joint oscillatory movements. AB - In the framework of the equilibrium-point hypothesis, virtual trajectories and patterns of joint stiffness were reconstructed during voluntary single-joint oscillatory movements in the elbow joint at a variety of frequencies and against two inertial loads. At low frequencies, virtual trajectories were in-phase with the actual joint trajectories. Joint stiffness changed at a doubled frequency. An increase in movement frequency and/or inertial load led to an increase in the difference between the peaks of the actual and virtual trajectories and in both peak and averaged values of joint stiffness. At a certain, critical frequency, virtual trajectory was nearly flat. Further increase in movement frequency led to a 180 degree phase shift between the actual and virtual trajectories. The assessed values of the natural frequency of the system "limb + manipulandum" were close to the critical frequencies for both low and high inertial loads. Peak levels and integrals of the electromyograms of two flexor and two extensor muscles changed monotonically with movement frequency without any special behavior at the critical frequencies. Nearly flat virtual trajectories at the natural frequency make physical sense as hypothetical control signals, unlike the electromyographic recordings, since a system at its natural frequency requires minimal central interference. Modulation of joint stiffness is assumed to be an important adaptive mechanism attenuating difference between the system's natural frequency and desired movement frequency. Virtual trajectory is considered a behavioral observable. Phase transitions between the virtual and actual trajectories are illustrations of behavioral discontinuities introduced by slow changes in a higher level control parameter, movement frequency. Relative phase shift between these two trajectories may be considered an order parameter. PMID- 1407548 TI - Conduction properties of spinal cord axons in the myelin-deficient rat mutant. AB - Spinal cords of myelin-deficient and normal age-matched (control) rats were removed and their conduction and pharmacological properties studied in an in vitro brain slice chamber. The conduction velocity of the myelin-deficient dorsal column axons was reduced to about 25% of control axons; however, the amyelinated myelin-deficient axons displayed refractory periods and the ability to sustain high-frequency action potential discharge similar to that of dorsal column axons in control rats. Pharmacological results suggest that the myelin-deficient dorsal column axons qualitatively express a normal complement of ion channels and receptors. The demonstration of a normal representation of channels and receptors on these axons supports the proposal that the oligodendrocyte, and not the axon, is the site of the primary defect in the myelin-deficient rat mutant. It is concluded that, unlike acutely demyelinated axons which display marked frequency dependent conduction block, amyelinated axons of the myelin-deficient rat spinal cord develop compensatory mechanisms to stabilize action potential conduction. PMID- 1407549 TI - Developmental regulation of parasympathetic nerve density by sympathetic innervation in the tarsal smooth muscle of the rat. AB - The developmental influence of sympathetic innervation on parasympathetic nerve density was investigated in the tarsal smooth muscle of the rat. Specificity of acetylcholinesterase staining as a marker for parasympathetic innervation was first determined by acute selective denervations. Excision of the ipsilateral superior cervical ganglion caused a 39% reduction in the density of acetylcholinesterase-positive nerves seven days later, indicating that sympathetic nerves contribute to cholinesterase-positive tarsal muscle innervation. Excision of the pterygopalatine ganglion concurrent with superior cervical ganglionectomy caused a virtually complete disappearance of acetylcholinesterase-positive innervation within seven days, indicating that non sympathetic cholinesterase-positive fibers derive from the pterygopalatine ganglion and are presumed to be parasympathetic. Analysis of the control population indicated that parasympathetic nerve density did not vary significantly between males and females, between the superior and inferior muscles, or in rats studied at four and 12 months of age. The influence of sympathetic innervation on parasympathetic nerve density during postnatal development was examined by conducting surgical sympathectomies on postnatal day 5 and quantifying acetylcholinesterase-positive nerve density at four months of age. Neonatal sympathectomy caused a 46% reduction in cholinesterase-positive nerve density beyond that which occurred in acutely sympathectomized adult controls. It is concluded that sympathetic innervation is required for developing parasympathetic nerves to attain their normal density within the rat tarsal muscle. This finding is consistent with the idea that sympathetic nerves can exert positive effects on parasympathetic nerve outgrowth during development. PMID- 1407550 TI - Behaviour-dependent changes in acetylcholine release in normal and graft reinnervated hippocampus: evidence for host regulation of grafted cholinergic neurons. AB - Grafted neurons obtained from the fetal basal forebrain can provide a functional cholinergic reinnervation of the hippocampal formation in rats with a lesion of the intrinsic septal cholinergic afferents. In the present experiments graft derived acetylcholine release in the hippocampus was studied by microdialysis in awake rats during different types of behaviours which are known to activate the innate septohippocampal cholinergic system and during different activity periods of the day-night cycle. Two types of basal forebrain grafts were studied: cell suspensions implanted into the hippocampus in rats with an aspirative lesion of the fimbria-fornix, and grafts of solid tissue implanted as a tissue bridge into the fimbria-fornix lesion cavity. Increased acetylcholine overflow was seen in both groups with grafts during sensory stimulation (by handling). The strongest response (50% increase in acetylcholine release) was seen in rats with solid basal forebrain grafts (equivalent to two-thirds of that seen in intact rats). Immobilization stress and motor activity (swimming) also resulted in increased, but more variable, acetylcholine release (+ 30%; about one-third of the normal response). None of these effects was seen in the control rats with fimbria-fornix lesion only. The two-fold difference in hippocampal acetylcholine release in normal animals between day and night was absent in both types of grafted rats. An acute knife-cut, transecting the connections between the solid basal forebrain graft and the host hippocampus, caused an immediate 75% reduction in acetylcholine release (similar to the effect of an acute fimbria-fornix transection in the normal rats) and the response to swimming was no longer evident. The results show that grafted cholinergic neurons can be functionally integrated into the host brain, allowing the grafted neurons to be activated in the correct behavioural contexts, although the changes in acetylcholine overflow were overall smaller and more variable than normal. The ability of the host to influence cholinergic graft activity, most probably mediated via activation of afferent host-graft connections, may contribute to the efficacy of basal forebrain grafts in the amelioration of behavioural impairments in animals with lesions of the forebrain cholinergic system. PMID- 1407551 TI - N-methyl-D-aspartate receptor complex in the hippocampus of elderly, normal individuals and those with Alzheimer's disease. AB - The various ligand binding sites of the N-methyl-D-aspartate receptor complex in the hippocampal formation and parahippocampal gyrus of Alzheimer's disease patients and age-matched normal individuals were examined using quantitative autoradiography. The hippocampus and parahippocampal gyrus of the normal elderly brain exhibited virtually identical distributions of L-[3H]glutamate, [3H]5 methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-iminemaleate ([3H]MK-801), [3H][(+/-)2-carboxypiperazine-4-yl]propyl-1-phosphonic acid ([3H]CPP) and strychnine-insensitive [3H]glycine binding sites (r greater than 0.87) suggesting that binding occurred to different domains of the same receptor macromolecule. The binding of [3H]MK-801 to channel-associated phencyclidine sites appeared to be most severely impaired in Alzheimer's disease, especially at the anterior hippocampal level. When the data were averaged and the means for Alzheimer's disease and control group compared, a 34% decrease (P less than 0.01) in [3H]MK 801 binding was identified in the CA1 stratum pyramidale and a smaller decrease was found in the dentate gyrus molecular layer, parahippocampal gyrus and subiculum. The CA1 region exhibited a similar 35% reduction (P less than 0.05) in L-[3H]glutamate binding to N-methyl-D-aspartate-sensitive sites. This decrease most probably reflected a decline in receptor density. Binding of [3H]CPP to antagonist-preferring sites and [3H]glycine to glycine modulatory sites did not change significantly. However, a marked intersubject variability in N-methyl-D aspartate receptor binding was observed in control and Alzheimer's disease groups. This variability was not related to age, sex or post mortem delay. Some Alzheimer's disease patients showed markedly reduced receptor binding levels, while others showed no changes or even increased binding. The loss of N-methyl-D aspartate-sensitive sites did not correlate with a loss of neurons in the CA1 region (r = 0.286). Similarly, no correlation between the level of binding to N methyl-D-aspartate-sensitive sites and the density of neuritic plaques and neurofibrillary tangles was found. Intersubject variability in N-methyl-D aspartate receptor responses in the Alzheimer's disease group may partially explain conflicting reports in the literature on the N-methyl-D-aspartate receptor changes in Alzheimer's disease, and imply that caution should be exercised before making any generalizations about receptor changes in Alzheimer's disease based on mean values only. The analysis of the individual Alzheimer's disease cases may also be valuable in determining the mechanism(s) underlying the disease. PMID- 1407552 TI - The neurofilament triplet is present in distinct subpopulations of neurons in the central nervous system of the guinea-pig. AB - It is commonly assumed that most, if not all, neurons contain the intermediate filament protein class known as the neurofilament protein-triplet. The following study investigated the distribution of neurofilament protein-triplet immunoreactivity in selected regions of the guinea-pig central nervous system using monoclonal antibodies directed against phosphorylation-independent epitopes on the three subunits under optimal tissue processing conditions. Neurofilament protein-triplet immunoreactivity was present in distinct subpopulations of neurons in the cerebellar cortex, neocortex, hippocampal formation, retina, striatum and medulla oblongata. In many of these regions, labelled neurons represented only a small proportion of the total. The selective distribution of this intermediate filament protein class was confirmed in double-labelling experiments using antibodies to the neurofilament protein-triplet in combination with antibodies to other neuronal markers. The distribution of neurofilament protein-triplet immunoreactivity also correlated with the distribution of staining observed with a silver impregnation method based on Bielschowsky. The present results in combination with previous observations have demonstrated that the neurofilament protein-triplet is found in specific subclasses of neurons in different regions of the nervous system. Content of this intermediate filament protein class does not appear to be correlated with neuronal size or length of projection. These results also suggest that the selectivity of staining between neuronal classes observed with classical silver impregnation methods may be due to the presence or absence of the neurofilament protein-triplet. The present results may also provide a new perspective on the basis of the selective vulnerability of neurons in degenerative diseases. PMID- 1407553 TI - Vestibularly induced slow oscillations in climbing fiber responses of Purkinje cells in the cerebellar nodulus of the rabbit. AB - In this report we describe an interesting form of plasticity in climbing fiber responses evoked in Purkinje cells of the rabbit cerebellum by periodic vestibular stimulation. The cerebellar nodulus receives a vestibular as well as a visual climbing fiber afferent input from the contralateral inferior olive. The vestibular input to the inferior olive originates from the ipsilateral medial and descending vestibular nuclei and terminates within the beta-nucleus. This projection to the beta-nucleus from secondary vestibular neurons is GABAergic. This means that vestibularly evoked activity of neurons in the beta-nucleus is controlled by modulation of an inhibitory input, rather than by modification of an excitatory input. We have recorded the climbing fiber responses of single Purkinje cells in the uvula-nodulus (lobules 9c, 9d and 10) of rabbits and we have characterized the climbing fiber response of each Purkinje cell from which we recorded by testing its sensitivity to otolithic stimulation, semicircular canal stimulation and optokinetic stimulation. Vestibularly evoked climbing fiber responses recorded from the left nodulus were stationary. They were repeatedly evoked, for tens of minutes, by sinusoidally rotating the rabbit about the longitudinal axis onto its left side (Fig. 1B). When the vestibular stimulus was stopped the discharge of these climbing fiber responses returned to non-periodic spontaneous levels. However, the vestibularly evoked climbing fiber discharge of approximately 5% of Purkinje cells was not stationary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407554 TI - Descriptive morphology of developing fetal neostriatal allografts in the rhesus monkey: a correlated light and electron microscopic Golgi study. AB - Primate fetal striatal neurons were transplanted into the ibotenic acid lesioned rhesus monkey striatum. Ten weeks after transplantation the monkeys were transcardially perfused and graft tissue was histologically stained. Golgi impregnated, and processed for electron microscopy. The monkeys received magnetic resonance imaging (MRI) scans before lesioning, after lesioning, and ten weeks after transplantation to noninvasively study the striatal grafts. The study demonstrated that fetal striatal grafts, measuring up to 0.4 x 0.8 cm, can survive for extended periods of time in the non-human primate. Hematoxylin-eosin stained sections of the transplant demonstrated that neuronal, glial, vascular, and lymphocytic cells were present in the graft. The majority of the neurons had somatic diameters between 8 and 20 microns and were characterized by nuclei containing multiple nucleoli. A few neurons within the graft had somatic diameters up to 40 microns. These larger neurons exhibited more mature cytoplasm containing a moderate amount of Nissl substance. Some of the blood vessels within the graft were surrounded by a large number of plasma cells, but there was no evidence of hemorrhage or necrosis. Bielschowsky staining and Golgi impregnation of the transplanted tissue demonstrated that there were neurons at various degrees of differentiation. Some of the neurons had varicose dendrites, growth cones, and filopodia, which are all characteristics of immature neurons, while others had a much more mature appearance, including a moderate number of dendritic spines. Some of these neurons had an appearance typical of differentiating "medium spiny" neurons of the normal striatum. Electron microscopic analysis of the transplanted tissue and individual Golgi-impregnated neurons within the transplant confirmed that there were developing neurons within the graft. These neurons had an increased nuclear-to-cytoplasmic ratio and had nuclei containing multiple nucleoli. The neuropil surrounding these neurons was loosely organized and contained large areas of extracellular space. The neuropil exhibited developing dendrites, numerous growth cones, and mature synapses. In summary, the study demonstrated that fetal striatal allografts can survive for up to three months in the rhesus monkey and undergo normal differentiation as assessed by Golgi impregnation and electron microscopy. PMID- 1407555 TI - Calretinin distribution in the thalamus of the rat: immunohistochemical and in situ hybridization histochemical analyses. AB - The distribution of calretinin-containing cells was examined by in situ hybridization histochemistry and compared with the immunohistochemical mapping of calretinin in the thalamus of the rat. Results revealed a close correspondence between the immunohistochemical localization of cell bodies and the messenger RNA label produced by the calretinin oligonucleotide probe. Calretinin cells were most prominent in the midline (paraventricular, reuniens, rhomboid) and intralaminar (central medial, paracentral) nuclei and in a group of cells along the rostral central gray which appeared continuous with the caudal extent of the midline nuclei. A subpopulation of calretinin cell bodies was also identified in the reticular nucleus. The mediorostral lateral posterior nucleus, subparafascicular, lateral geniculate and habenular nuclei also contained calretinin messenger RNA probe label. In contrast, no positive cells were found in the anterior, ventral or posterior thalamic nuclei. The distribution of calretinin cells did not correspond directly with that of other histochemical markers. Thus, the in situ hybridization histochemical and immunohistochemical results revealed calretinin as a unique identifying marker for distinct sets of thalamic neurons. PMID- 1407556 TI - Microstimulation mapping of the basal forebrain in the anesthetized rat: the "preoptic locomotor region". AB - Previous studies have indicated that the basal forebrain at the level of the preoptic area contains neurons which participate in the initiation of locomotion. This study attempted to localize those neurons by mapping sites at which 25- and 50-microA stimulation (50 Hz, 0.5 ms cathodal pulses, 10-s trains) initiated hindlimb stepping. Anesthetized rats were held in a stereotaxic apparatus supported by a sling so that stepping movements rotated a wheel. Anesthesia was maintained by periodic injections of Nembutal (7 mg/kg) supplemented by lidocaine injections. Stimulation was applied through 50-70-microns diameter pipettes filled with 2 M NaCl at approximately 1600 sites in the basal forebrain, adjacent thalamus, and striatum. A circumscribed grouping of 25-microA locomotor sites, centered in the lateral preoptic area, defined the preoptic locomotor region. It extended into the ventral bed nucleus of the stria terminalis, the lateral part of the medial preoptic area, the anterior hypothalamic area, the medial and rostral parts of the ventral pallidum, medial substantia innominata, and the horizontal limb of the diagonal band. This general region is known to project to the midbrain locomotor region and the ventral tegmental area; it is proposed to initiate locomotion in service of primary motivational systems. Among the structures generally negative for locomotor sites were the dorsal and ventral striata, septal complex, bed nucleus of stria terminalis, and lateral ventral pallidum and substantia innominata. These findings indicate that low current stimulation applied to a circumscribed area centered in the lateral preoptic area produces locomotor stepping in the anesthetized rat. Whether the activated elements in this preoptic locomotor region are cells or fibers is not yet known. The degree of localization afforded by these findings indicates that the areas that are most likely to contain the mediating elements are quite limited in extent. PMID- 1407557 TI - Changing pattern of c-FOS expression in spinal cord neurons after electrical stimulation of the chronically injured sciatic nerve in the rat. AB - Immunocytochemical technique was used to study the distribution of c-FOS protein immunoreactive cells in the spinal cord and gracile nuclei 2 h after electrical stimulation of the sciatic nerve in ketamine/xylazine/acepromazine-anesthetized adult rats. Quantitative examination of the c-fos-labeled cells in the spinal cord laminae was made in unoperated and sham operated controls, after sciatic nerve transection without electrical stimulation, and after electrical stimulation at C-fiber or A alpha/beta-fiber intensity, both in normal animals and at various survival times after chronic sciatic nerve injury (transection and ligation) or crush. Unoperated animals showed very few c-fos-labeled cells, and sham operated controls showed labeled cells located mainly outside the sciatic nerve projection territory. A small increase in number of c-fos protein positive cells was seen after sciatic nerve transection without electrical stimulation. Stimulation of the normal sciatic nerve at C-fiber intensity resulted in c-fos protein-positive cells within the sciatic projection territory in the ipsilateral dorsal horn. Labeled cells were seen in all spinal cord laminae except lamina IX, with the vast majority in lamina I and outer lamina II. No labeled cells were seen in the gracile nucleus. Stimulation at A alpha/beta fiber intensity resulted in no or only a very small number of c-fos-positive neurons. Electrical stimulation of the injured sciatic nerve at C-fiber intensity, using the uninjured contralateral side as control, resulted in significant decreases in c fos-immunoreactive cells in lamina I plus the outer portion of lamina II at 12 and 39 days survival after injury. A non-significant decrease was seen in these laminae also after 21 days. Significant increases were seen in laminae III and IV at 21 days. Decreases in laminae V, VI and more ventral laminae were significant at 21 and 39 days after injury. At longer survival times, the difference between the normal and injured side seen weeks after injury tended to disappear. Stimulation at A alpha/beta fiber intensity 21 days after injury resulted in increases in the numbers of labeled cells in ipsilateral laminae II, III and IV and in the gracile nucleus. Sciatic nerve stimulation after crush injury resulted in more variable side differences, with tendencies for the same alterations as those noted after chronic transection-ligation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1407558 TI - Inflammatory mediators and nociception in the joint: excitation and sensitization of slowly conducting afferent fibers of cat's knee by prostaglandin I2. AB - The effects of prostaglandin I2 on the discharge properties of fine articular afferents (group III and group IV fibers) in the cat were examined by extracellular recordings from single units dissected from the medial articular nerve of the knee joint. Prostaglandin I2 was applied intra-arterially close to the joint in doses of 0.3-30 micrograms per 0.3 ml bolus injection, and its effects on the spontaneous activity as well as on discharges evoked by mechanical and chemical stimulation (bradykinin) were monitored. Prostaglandin E2 was also applied and the effects of prostaglandins I2 and E2 on particular units were compared. An excitatory effect of prostaglandin I2 was observed in 49% of 37 group III and in 37% of 27 group IV units. A sensitization to passive movements of the joint occurred in 71% of 31 group III and 48% of 21 group IV units. Sixty seven per cent of 32 units (groups III and IV) were both excited and sensitized by prostaglandin I2 to movements of 27% were sensitized but not excited. In 64% of 11 group III and 63% of eight group IV units studied the responses to bradykinin were enhanced by prostaglandin I2. Prostaglandin E2 had qualitatively similar effects as prostaglandin I2 but excited and sensitized a lower proportion of articular afferents. Forty-one per cent of the units were sensitive to both prostaglandins but 26% of the fibers were only sensitive to prostaglandin I2. None of the units was exclusively sensitive to prostaglandin E2. In general, the excitatory and sensitizing effects of prostaglandin E2 had a longer duration than those exerted by prostaglandin I2. We conclude that prostaglandin I2 increases the sensitivity to mechanical stimuli as well as to chemical stimulation by bradykinin in the majority of articular group III and group IV fibers. Moreover, in a large proportion of articular afferents, prostaglandin I2 had an excitatory effect. Thus, prostaglandin I2 may be an inflammatory mediator which is important for inflammation-evoked activity in slowly conducting afferents and it may participate in the development of arthritic hyperalgesia and pain. PMID- 1407559 TI - B-50/GAP43 localization in polarized hippocampal neurons in vitro: an ultrastructural quantitative study. AB - Hippocampal pyramidal neurons cultured in vitro gradually develop morphologically and biochemically distinct axons and dendrites, resulting in functional neuronal polarization [Dotti C. G. et al. (1988) J. Neurosci. 8, 1454-1468]. We have studied the distribution of the growth-associated protein B-50 in hippocampal neurons of the rat at stage 3 of development by means of light and electron microscopic immunocytochemistry. Hippocampal neurons grown for two to three days in vitro were aldehyde fixed and immunolabelled using polyclonal rabbit antibodies to B-50 and goat anti-rabbit immunoglobulins tagged with 1 nm gold particles. In order to permit visualization by both light and electron microscopy, the gold probes were silver intensified. Light microscopy demonstrated the absence of B-50 immunostaining in living neurons and the presence after permeabilization by fixation and subsequent treatment of the neurons with sodium borohydride, indicating that B-50 is located intracellularly. Both immunofluorescence and immunogold-silver labelling revealed that B-50 immunoreactivity outlined all neurites of the morphologically polarized neurons. For quantitative electron microscopy, six morphologically polarized neurons (developmental stage 3) were carefully selected from immunolabelled Epon-embedded neurons and processed completely to ultrathin sections. In this way the ultrastructural localization of B-50 has been studied in the cell body, the neurites and their growth cones. For each sectioned neuron, the relative distribution of the gold-silver deposits (representing B-50) over the plasma membrane of various cellular compartments was quantitated. B-50 is located at the plasma membrane of the neuronal cell body and all neurites including their growth cones. The density of B-50 on the plasma membrane of growth cones is not different from that of the neuritic shaft. In addition, B-50 is present on the cytosolic side of the membrane of small electron-lucent vesicles (average diameter 102.7 +/- 2.5 nm) resembling transport vesicles. These vesicles are present in the cell body and the neurites. A two-fold concentration is found in the central region of the growth cones, suggesting a role of these vesicles in axonal transport, membrane insertion and (or) recycling. Since, at the onset of neuronal polarization, B-50 is present at the plasma membrane in all compartments of the hippocampal neuron, we suggest that at this stage of development B-50 does not participate directly in the processes leading to morphological polarization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1407560 TI - Endopeptidase-24.11 is suppressed in myelin-forming but not in non-myelin-forming Schwann cells during development of the rat sciatic nerve. AB - Endopeptidase-24.11, which is identical with the common acute lymphoblastic leukemia antigen (CALLA), is a cell surface zinc metalloprotease that has the ability to hydrolyse a variety of physiologically active peptides. Interest in this enzyme is based on the view that it may play a role in the regulation of peptide signals in different tissues, including the nervous and immune systems. We have previously shown that endopeptidase-24.11 is present in Schwann cells in the peripheral nervous system of newborn pigs [Kioussi C. and Matsas R. (1991) J. Neurochem. 57, 431-440]. In the present study we have investigated the developmental expression of the endopeptidase by Schwann cells in the rat sciatic nerve, from embryonic day 16 to maturity. Endopeptidase-24.11 was monitored enzymatically as well as by immunoblotting and immunocytochemistry using the monoclonal anti-endopeptidase antibody 23B11. We found an age-dependent decline in both the enzyme activity and the levels of immunoreactive protein. Endopeptidase-24.11 was first detected at embryonic day 18 and was present in all neonatal and early postnatal Schwann cells. However, as myelination proceeded the endopeptidase was gradually suppressed in the majority of cells that form myelin but retained in non-myelin-forming cells in the adult animal. At this stage, only very few large diameter myelinated fibers expressed weakly endopeptidase-24.11. Schwann cells dissociated from postnatal day 5 nerves and cultured up to one week in the absence of axons expressed endopeptidase-24.11. These results show that the endopeptidase has a distinct developmental profile in the rat sciatic nerve, similar to that of a group of other Schwann cell surface antigens, including the cell adhesion molecules N-CAM and L1 and the nerve growth factor receptor. We suggest that, as is the case with these antigens, endopeptidase-24.11 may play a role in nerve development and/or regeneration. In addition, persistence of endopeptidase-24.11 in a minority of adult myelin-forming Schwann cells suggests a possible role for the enzyme in axon-myelin apposition and maintenance, especially of larger diameter axons. PMID- 1407561 TI - Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat. AB - Recent evidence has shown that activation of the N-methyl-D-aspartate receptor mediates the thermal hyperalgesia produced in a model of neuropathic pain. As the acute nociceptive effects of N-methyl-D-aspartate have been reported to be mediated through production of nitric oxide and activation of soluble guanylate cyclase, these experiments were designed to determine whether the thermal hyperalgesia produced in a rat model of neuropathic pain is also mediated through the production of nitric oxide and activation of soluble guanylate cyclase. Loose ligation of the sciatic nerve with chromic gut sutures, but not bilateral sham rats, demonstrated evidence of a marked thermal hyperalgesia on day 3 post surgery. In bilateral sham rats, intrathecal administration of either an alternate substrate for nitric oxide synthase, NW-nitro-L-arginine methyl ester, or the soluble guanylate cyclase inhibitor, Methylene Blue, did not produce any change in thermal nociceptive withdrawal latencies. These same treatments blocked the thermal hyperalgesia in rats with chromic gut ligatures for a period of 2 and 4 h, respectively. These results suggest that a sustained production of nitric oxide and subsequent activation of soluble guanylate cyclase in the lumbar spinal cord mediate the thermal hyperalgesia produced in a model of neuropathic pain in the rat. PMID- 1407562 TI - Epidermal growth factor affects both glia and cholinergic neurons in septal cell cultures. AB - The effects of epidermal growth factor on high density primary cultures of fetal (embryonic day 17) rat septal cells were examined. Under serum-free conditions, the continuous exposure of these cultures to epidermal growth factor for seven days significantly decreased choline acetyltransferase (EC 2.3.1.6) activity in a dose-dependent manner. Maximal decreases were observed from 1 to 10 ng/ml epidermal growth factor. This effect was completely abolished by the addition of anti-epidermal growth factor antibodies. The epidermal growth factor-mediated decrease in choline acetyltransferase activity was culture-time dependent, being first detectable after five days of factor application and may likely represent an inhibition of the spontaneous increase in enzyme activity that occurs with time in culture. Concomitant with changes in enzyme activity, epidermal growth factor produced a significant and proportional decrease in the number of acetylcholinesterase-positive neurons. This decrease in acetylcholinesterase positive cells did not reflect a decrease in cholinergic cell survival as nerve growth factor could restore the number of acetylcholinesterase-positive neurons in epidermal growth factor-treated cultures to control levels. Furthermore, in these high-density cultures, epidermal growth factor did not affect general neuronal survival, while it did produce an increase in the number and intensity of glial fibrillary acidic protein-immunoreactive astroglia as well as in the number of macrophage-like cells. The proliferative response of these non-neuronal cells to epidermal growth factor, as assessed by [3H]thymidine incorporation, was evident after three days of epidermal growth factor application, persisted thereafter, and could be antagonized by the inclusion of the antimitotic 5 fluorodeoxyuridine. Furthermore, 5-fluorodeoxyuridine completely blocked the epidermal growth factor-mediated decrease in choline acetyltransferase activity. However, when epidermal growth factor was tested in pure glial cultures, it only directly induced proliferation of astrocytes. These results suggest that the proliferative response of either one or both of these glial cell types in the mixed cultures may be indirectly affecting cholinergic cell expression. PMID- 1407563 TI - Basic fibroblast growth factor-like immunoreactivity in Purkinje cells of the rat cerebellum. AB - An antiserum against basic fibroblast growth factor was characterized by immunoblot experiments and used to investigate immunohistochemically the projection fields and fine structures of basic fibroblast growth factor containing cerebellar Purkinje cells. The antiserum demonstrated clearly purified basic fibroblast growth factor and basic fibroblast growth factor-like molecules of the same molecular weight in homogenates of the adult rat cerebellum. Light and electron microscopic immunohistochemistry revealed that a large number of Purkinje cells, if not all, send immunoreactive dendrites to the molecular layer and basic fibroblast growth factor-containing axons to the deep cerebellar and lateral vestibular nuclei, where basic fibroblast growth factor nerve terminals form synapses with the soma and dendrites of neurons labeled weakly with basic fibroblast growth factor. Nerve cells with basic fibroblast growth factor had immunoreaction deposits mainly in free ribosomes, those attached to the endoplasmic reticulum and in the nuclear euchromatin. These findings suggest that basic fibroblast growth factor is present in cerebellar Purkinje cells and undergoes two modes of transport, one to axon terminals and the other to nuclear euchromatin, known as the RNA transcription zone. PMID- 1407564 TI - Amplification signals anticipation--less DNA is better. PMID- 1407565 TI - Anticipation in myotonic dystrophy. I. Statistical verification based on clinical and haplotype findings. AB - To determine whether anticipation in myotonic dystrophy (DM) is a true biologic phenomenon or an artifact of ascertainment bias, we studied 201 members of nine DM kindreds, including 67 individuals with the clinical diagnosis of DM. Of 49 parent-child pairs in which both the parents and the children were clinically affected, the onset of DM occurred in an earlier decade of life in the child than the parent in 44 pairs and in the same decade in five pairs (p < 0.001). To eliminate direct ascertainment bias, we excluded nine pairs involving the index patients. Indirect ascertainment bias due to incomplete penetrance was unlikely, since 55% of the children of DM parents had DM. However, by haplotype analysis of restriction fragment length polymorphisms, we diagnosed DM in one of the 42 asymptomatic children of affected parents and excluded DM in twenty-eight. We estimated that patients with early-onset DM would have produced an additional 25 DM children if they had normal fertility and nuptiality. Assuming that the expected age-of-onset distribution occurs without anticipation in these 25, only seven would have had the onset of DM earlier than their parents. With the corrected result, the child would have been affected earlier than the parent in 53 pairs, and the parent would have been affected at the same age as or earlier than the child in 13 pairs (p < 0.001). Thus, the observed anticipation is unlikely to be totally attributable to ascertainment bias, suggesting the potential importance of biologic mechanisms. PMID- 1407566 TI - Anticipation in myotonic dystrophy. II. Complex relationships between clinical findings and structure of the GCT repeat. AB - We studied the expansion of the GCT repeats within the myotonic dystrophy protein kinase gene in nine myotonic dystrophy (DM) kindreds. Southern blot and polymerase chain reaction analyses of the repeat region demonstrated the expansion in all 62 patients with the diagnosis of DM. Among 43 DM parent-child pairs, age of onset in the child was earlier than in the parent in 36 pairs, in the same decade as the parent in five, and undetermined in two. The clinical anticipation observed in the 36 pairs accompanied an increase in the fragment size in 32, a decrease in two, and no apparent change in two pairs. In the remaining pairs without documented clinical anticipation, the fragment size increased in four, decreased in two, and was apparently unchanged in one. Overall, the size of expansion showed an inverse correlation with the age of onset (p < 0.001). In all seven pairs in which the fragment did not increase in size, the affected parent was male. Two congenital DM children born to affected mothers had expanded DNA greater than 4.5 kb. The differences between parent and child in age of onset significantly correlated with the differences in the expansion size among father-child pairs (p < 0.001) but not mother-child pairs (p > 0.5). Our data suggest that the expansion of the GCT repeats plays an important role in anticipation although other factors, including the sex of the affected parent, may have significant effects on molecular mechanisms of anticipation. PMID- 1407567 TI - Post-lumbar puncture headaches: experience in 501 consecutive procedures. AB - To ascertain the frequency and risk factors for post-lumbar puncture headache, we studied all adults who had an ambulatory lumbar puncture (LP) in a 1-year period. Patients filled out a questionnaire detailing their headache experience on the day of, and the 6 days following, LP. Those who did not return the questionnaire were telephoned. We systematically collected and analyzed many items, including the lumbar puncturist's experience, the degree of difficulty of the LP, CSF findings, final diagnosis, and the patient's demographic characteristics. Patients reporting headache before LP were more likely to report post-LP headaches. In addition to this, younger female patients with a lower body mass index have the highest risk of developing post-LP headaches. CSF opening pressure, cells, and protein, patient's position during LP, the duration of recumbency following LP, and the amount of CSF removed at the time of LP did not influence the occurrence of headache. PMID- 1407568 TI - The epidemiology of myasthenia gravis in central and western Virginia. AB - We conducted a study of the epidemiology of myasthenia gravis (MG) in four locations in central and western Virginia from 1970 through 1984. The population surveyed was 555,851 in 1984. A total of 73 new cases of MG occurred during the survey period, producing an overall average annual incidence rate of 9.1 per million. The point prevalence rate in 1980 was 13.4 per 100,000, and in 1984 it was 14.2. Approximately 15% of the population was black, and we found that incidence and prevalence rates for the black population were higher than the corresponding white population. When the population was subdivided into <50 and 50+ age groups, the incidence and prevalence were significantly higher in the older group. The rates we report here are higher than rates reported from any other locality. The reasons for the higher rates include optimal case identification, survey of a population with a higher incidence, and increasing aging of the population. PMID- 1407569 TI - Parkinson's disease in twins studied with 18F-dopa and positron emission tomography. AB - We used 18F-dopa PET to examine concordance for dysfunction of the nigrostriatal dopaminergic system in 18 co-twins of patients with Parkinson's disease (PD) and scanned one clinically concordant monozygotic (MZ) twin pair, 17 asymptomatic co twins (10 MZ, 7 dizygotic [DZ]), and 13 twins with PD (8 MZ, 5 DZ). Mean 18F-dopa uptake of the twins with PD was significantly reduced in putamen to 38% and in caudate to 66% of normal. Mean putamen 18F-dopa uptake for the 17 asymptomatic co twins was also significantly reduced (86% of normal), as was putamen tracer uptake for the 10 MZ (87% of normal) and seven DZ (83% of normal) asymptomatic co twin subgroups. Four of 10 MZ and two of seven DZ asymptomatic co-twins had putamen 18F-dopa uptake reduced more than 2 SDs below the normal mean. Three of these four asymptomatic MZ co-twins had tremor on examination at the time of PET and one has now developed PD 2 years later. Our PET findings give concordances for nigral dysfunction of 45% in the MZ pairs and 29% in the DZ pairs at a 2-SD threshold, and 18% in MZ and 0% in DZ pairs at a 3-SD threshold of significance. These data suggest that the concordance for nigral pathology in PD twins may be higher than previously realized and that the presence of an isolated postural or rest tremor may be a phenotypic expression of PD. PMID- 1407570 TI - Prevalence of Parkinson's disease and other types of parkinsonism: a door-to-door survey in three Sicilian municipalities. The Sicilian Neuro-Epidemiologic Study (SNES) Group. AB - We investigated the prevalence of Parkinson's disease and other types of parkinsonism in a Sicilian population using a door-to-door two-phase approach. This design called for the administration of a brief screening instrument to all subjects who, on November 1, 1987, were residents of Terrasini (Palermo Province), Santa Teresa di Riva (Messina Province), and Riposto (Catania Province), Sicily (N = 24,496). Study neurologists using specified diagnostic criteria extensively investigated those subjects who screened positive. We found 63 subjects affected by Parkinson's disease, 21 with secondary parkinsonism, and seven with unspecified parkinsonism. The crude prevalence per 100,000 population was 371.5 for all types of parkinsonism and 257.2 for Parkinson's disease; for both entities, prevalence increased steeply with age and showed an inconsistent sex pattern. Our prevalence figures for Parkinson's disease are higher than those previously reported in Italy or elsewhere, which may be due, in part, to more complete case-ascertainment. PMID- 1407571 TI - Multiple sclerosis with very late onset. AB - Multiple sclerosis (MS) can present clinically after age 59, but only rarely. In a large MS population (N = 2,019), 0.6% of patients had their first symptom at age 60 or older. Of this group, six had clinically definite MS, two had laboratory-supported definite MS, and four had clinically probable MS. The onset at this age was characteristically a slow deterioration of motor function. Most (10 of 12) of these very late-onset patients had a progressive course of disease from onset. PMID- 1407572 TI - National General Practice Study of Epilepsy (NGPSE): partial seizure patterns in a general population. AB - The National General Practice Study of Epilepsy (NGPSE) is a prospective community-based study of newly diagnosed epileptic seizures. Of 594 patients with definite epileptic seizures, 160 (26.9%) had seizures with a clinically localizable onset: 36 (22.5%) frontal, 52 (32.5%) central sensorimotor, 43 (27%) temporal, nine (5.6%) frontotemporal, and 10 each (6.3%) parietal and other posterior cortex. There was no difference among these groups in seizure frequency or remission rate; 46.5% were seizure free and 6.9% had severe epilepsy. Etiology was identifiable in 41% and focal CT and EEG abnormalities in 33% and 19%, with results discordant with the clinical seizure localization in 21% and 20%. Temporal lobe epilepsy may be underreported, as it may be more difficult to localize clinically. Extratemporal seizures are extremely common in the general population, especially frontal and central sensorimotor, in relation to cerebrovascular disease. Prognoses are similar for partial epilepsies with different clinical patterns and regions of onset and are much better than suggested in hospital-based studies. The clinical, EEG, and CT localizations may frequently be discordant in this nonrefractory group. PMID- 1407573 TI - Localization of emotional and volitional facial paresis. AB - Emotional facial paresis is characterized by impaired activation of face muscles with emotion but normal voluntary activation. We report seven patients with this sign. Their lesions involved the frontal lobe white matter, the striatocapsular territory, the anterolateral thalamus and insula, the posterior thalamus and operculum, and the mesial temporal lobe and insula each in one patient, and the posterior thalamus in two patients. Volitional facial paresis affects facial movements with voluntary effort, sparing activation on emotion. We report four such patients, with lesions involving the motor cortex in one and the pyramidal tract in the cerebral hemisphere in three. PMID- 1407574 TI - HIV-1 infection and intravenous drug use: longitudinal neuropsychological evaluation of asymptomatic subjects. AB - A previous baseline cross-sectional comparison of cognitive performance of a group of AIDS-free, HIV-seropositive intravenous drug users with seronegative control intravenous drug users revealed no significant differences attributable to HIV. We now present longitudinal follow-up results from the same cohort of 160 intravenous drug users. There were no differences in performance by serostatus group at either 6- or 12-month follow-up visits, although differences by age and education were observed. Improvement in performance secondary to practice effects was comparable in both serostatus groups. These findings confirm that chronic intravenous drug use may be associated with a wide range of neuropsychological deficits, but there is no evidence that such preexisting deficits interact with HIV infection to produce additional cognitive impairment in otherwise asymptomatic intravenous drug users. Together with results from other high-risk groups such as homosexual/bisexual men and hemophiliacs, these results confirm that neurocognitive abnormalities during the presymptomatic stages of HIV infection are rare, regardless of the route of acquisition of the virus. PMID- 1407575 TI - Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. AB - We reviewed the clinical findings in 55 patients with cerebellar degeneration associated with the anti-Yo antibody (an anti-Purkinje cell antibody identified in this study by histochemistry and Western blot). The patients were all women, 26 to 85 years old. Fifty-two of them proved to have malignancies, almost exclusively breast or gynecologic cancers and usually confined to the involved organs and local lymph nodes. One woman had adenocarcinoma of the lung, and in three no malignancy has yet been identified. In 34 of 52 patients with cancer, the neurologic syndrome preceded the diagnosis of cancer and in many led to that diagnosis. Patients subacutely developed a pancerebellar disorder that was substantially disabling in most, with 37 of 48 assessable patients being unable to walk or sit unassisted. Laboratory evaluation revealed lymphocytic pleocytosis in 35 patients, with eventual cerebellar atrophy on imaging studies in seventeen. The disabling neurologic syndrome generally did not respond to treatment, but the cancer was often successfully treated. The presence of the anti-Yo antibody in patients with cerebellar symptoms warrants an aggressive approach to diagnosis and treatment of the underlying cancer, as many are curable at the time neurologic symptoms develop. PMID- 1407576 TI - Paraneoplastic cerebellar degeneration. II. Clinical and immunologic findings in 21 patients with Hodgkin's disease. AB - We reviewed clinical findings and serologic data on 18 men and three women with paraneoplastic cerebellar degeneration (PCD) associated with Hodgkin's disease (HD). The patients were 20 to 77 years old (median, 44). The lymphoma preceded neurologic symptoms by 1 to 54 months in 17/21 patients, but stage or activity did not correlate with severity of neurologic disease; six developed PCD while in HD remission. PCD evolved subacutely (over weeks to months) and was pancerebellar in most. Ten had downbeat nystagmus. Thirteen stabilized in a disabled state (wheelchair- or bed-bound), five stabilized ambulatory, and three, who had progressed to a nonambulatory state, recovered. The clinical findings were usually only cerebellar but one patient had an encephalopathy, three long-tract signs, and two sensory neuropathy. Plasmapheresis (seven patients) and corticosteroids or other immunosuppressant medication (eight patients) did not help; one improved dramatically after treatment with clonazepam. Two patients improved spontaneously. Six patients had serum antibodies that reacted specifically with Purkinje cells. The pattern was distinct from that of PCD with gynecologic cancer (anti-Yo) or small-cell lung cancer (anti-Hu). Western blotting failed to identify a discrete Purkinje cell antigen. Seropositive patients did not differ clinically from their seronegative counterparts. HD associated PCD is more common in men and in a younger age group than in PCD with other malignancies. PMID- 1407577 TI - Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome. AB - We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum. PMID- 1407578 TI - Magnetic brain stimulation: the silent period after the motor evoked potential. AB - In 25 normal subjects, we studied the EMG silent period following the magnetic motor evoked potential (MEP) when the target muscle was tonically contracted (post-EMP silent period [PMSP]). In the first dorsal interosseous muscle (FDI), PMSP duration increased in linear proportion to stimulus intensity, but not to the size of the preceding MEP. The PMSP was longer in hand and forearm muscles than in upper arm muscles. In the FDI, PMSP was longer than the peripheral silent period (PSP) even when multiple peripheral stimuli were used to get M responses whose twitch force was equivalent to that of MEPs. Weak magnetic stimuli evoked silent periods preceded by no MEP in several subjects. Spinal alpha-motoneurons (alpha-MNs) were partially inhibited during the first PMSP portion, but later this effect recovered. MEPs due to weak electrical stimuli to motor cortex were only slightly inhibited during the late PMSP. Segmental inhibitory loops evoked by the muscle twitch and inhibitory projections descending to alpha-MNs from the cortex predominantly underlie earlier PMSP portions, but recurrent intracortical inhibition may also contribute. Later portions are predominantly due to other stimulus-related cerebral inhibitory or suppressing phenomena. PMID- 1407579 TI - Differential effects of congenital versus acquired unilateral brain injury on dichotic listening performance: evidence for sparing and asymmetric crowding. AB - We assessed dichotic speech and complex-pitch discrimination in nine young patients with unilateral left-hemisphere injury and eight young patients with unilateral right-hemisphere injury incurred in the pre-perinatal (congenital) period. As in adults with acquired unilateral lesions, both congenital lesion groups demonstrated poor performance on stimuli presented to the ear contralateral to the lesion. In overall performance on speech discrimination, however, the left-hemisphere congenital lesion group performed significantly better than the acquired-lesion group did. On complex-pitch discrimination, the right-hemisphere congenital lesion group performed significantly better than did the acquired-lesion group, but both left- and right-hemisphere congenital lesion groups were significantly worse at complex-pitch discrimination than were their age- and gender-matched normal controls. These results indicate that although congenital damage produces a "lesion effect" in dichotic listening similar to that after damage acquired in adulthood, overall function is relatively spared. To the extent that complex-pitch discrimination is affected by congenital damage to either hemisphere but speech discrimination is not, the present results are consistent with an asymmetric form of crowding during reorganization after congenital unilateral brain damage. PMID- 1407580 TI - Confusion and memory loss from capsular genu infarction: a thalamocortical disconnection syndrome? AB - We examined six patients with an abrupt change in behavior after infarction involving the inferior genu of the internal capsule. The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation, suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia occurred in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients showed a focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. We infer that the capsular genu infarct interrupted the inferior and anterior thalamic peduncles, resulting in functional deactivation of the ipsilateral frontal cortex. These observations suggest that one mechanism for cognitive deterioration from a lacunar infarct is thalamocortical disconnection of white-matter tracts, in some instances leading to "strategic-infarct dementia." PMID- 1407581 TI - Ictal head deviation: lateralizing significance of the pattern of head movement. AB - To resolve the controversy surrounding the lateralizing value of ictal head deviation, we analyzed head-turning movements in relation to the actions of the two divisions of the sternocleidomastoid muscle. In 12 (75%) of 16 patients with surgically confirmed lateralized seizure foci, the face rotated upward and contraversive to the hemisphere of seizure origin, consistent with activation of the ipsilateral sternomastoid muscle. One patient showed a sustained, downward ipsiversive head tilt consistent with the action of the ipsilateral cleidomastoid muscle, and three patients had a combined ipsiversive head tilt and contraversive face rotation. No patient exhibited ipsiversive upward face rotation or contraversive head tilting, as would be expected if the contralateral sternocleidomastoid were activated. Our findings indicate that hemispheric seizure foci activate one or both divisions of the ipsilateral sternocleidomastoid muscle. Accurate lateralization of the seizure focus is possible only when ictal head deviation is assessed in the context of the different actions of the sternomastoid and cleidomastoid muscle divisions. PMID- 1407582 TI - Specific neurobehavioral profile of Williams' syndrome is associated with neocerebellar hemispheric preservation. AB - Previous work demonstrated enlargement of the neocerebellar vermis in Williams' syndrome (WS), despite diminished volumes in the cerebral hemispheres. We present the first in vivo volumetric study of any structure within the cerebellar hemispheres. Using MRI, we identified and reliably measured the neocerebellar tonsils in WS subjects; Down's syndrome (DS) subjects matched for age, IQ, and cerebral volume; and age-matched normal controls. WS tonsils were equal in size to control tonsils and larger than DS tonsils. In proportion to the cerebrum, WS tonsils were larger than controls'. These results coincide with the remarkable neuropsychological preservation of language and affect in WS, despite general cognitive impairment. They contrast with the neocerebellar vermal hypoplasia seen in autism, with its communicative and affective deficits. Additionally, two WS subjects showed Chiari type I malformations, but the average tonsillar position in WS was not found to be different than in controls. PMID- 1407583 TI - Valproate acute administration, EEG epileptic abnormalities, and ammonemia. AB - Acute, oral administration of 14.3 to 37.5 mg/kg magnesium valproate (peak serum concentrations, 65 to 139 micrograms/ml) increases spike-wave frequency at 2, 3, 4, and 5 hours postdrug, in the absence of hyperammonemia or significant correlations with ammonemia fluctuations. This observation suggests a direct role of valproate on neural activity. PMID- 1407584 TI - Amphotericin B-associated leukoencephalopathy. AB - We report instances of fatal leukoencephalopathy associated with the intravenous administration of the antifungal agent amphotericin B (AmB) to a 16-year-old girl treated for acute lymphoblastic leukemia and a 22-year-old man who underwent bone marrow transplantation for a myelodysplastic syndrome. Both received AmB in association with cranial irradiation and developed a subacutely evolving neurologic disorder characterized by personality change and confusion rapidly progressing to akinetic mutism. Neuroimaging studies disclosed diffuse nonenhancing abnormalities of the cerebral, particularly frontal, white matter that included hypodensity on CT and increased signal on T2-weighted MRI. Postmortem examinations demonstrated a diffuse, noninflammatory leukoencephalopathy with florid astrogliosis, demyelination, and infiltration of the hemispheric white matter by foamy macrophages. In neither case was there evidence of opportunistic infection or neoplastic infiltration of the nervous system. We review the evidence that polyene macrolide antibiotics such as AmB are potential leukotoxins. PMID- 1407585 TI - Lateralization of human focal epilepsy by 31P magnetic resonance spectroscopic imaging. AB - We attempted to lateralize the epileptogenic focus (seven temporal lobe hippocampal foci, one frontal lobe focus) in medically refractory unilateral complex partial seizures, using noninvasive 31P magnetic resonance spectroscopic imaging (MRSI) blindly and interictally to compare hippocampal or frontal regions. The seizure foci were more alkaline (intracellular pH = 7.17 +/- 0.03) compared with the contralateral region (7.06 +/- 0.02, p < 0.01) in all eight cases; the inorganic phosphate was relatively increased (240 +/- 50% of contralateral, seven of eight cases, p < 0.01); and phosphomonoesters were relatively reduced (68 +/- 9% of contralateral, seven of eight cases, p < 0.01). Other phosphorus metabolites were symmetric (+/- 10%). 31P MRSI correctly lateralized the seizure focus in all eight cases. By comparison, imaging correctly lateralized four cases and SPECT, two cases. In conclusion, 31P MRSI is a useful tool for the noninvasive clinical assessment of focal epilepsy and can accurately lateralize the epileptogenic focus. PMID- 1407586 TI - Amyloidoma of the CNS. I. Clinical and pathologic study. AB - We report a 32-year-old man with a 4-year history of headaches, seizures, and dementia secondary to multifocal amyloidomas in the white matter. Immunohistochemical and electron microscopic analyses suggest that the amyloidomas resulted from processing of plasma-cell-derived amyloidogenic protein by microglial cells. PMID- 1407587 TI - Longitudinal changes in lateral ventricular volume in patients with dementia of the Alzheimer type. AB - We determined the rates of lateral ventricular enlargement and decline in cognitive performance for 11 men and nine women with dementia of the Alzheimer type (DAT), and compared these rates with the same measures obtained for age matched healthy controls (nine men and eight women). DAT patients, as a group, had only mild cognitive impairment at initial evaluation, and each patient was followed from 9 months to over 7 years with yearly evaluations. Six DAT patients had isolated memory impairment as their only cognitive deficit early in the course of the disease. The rate of total lateral ventricle enlargement (cm3/yr) was significantly different between DAT and healthy controls, and was more specific and sensitive to the diagnosis of DAT than comparison of cross-sectional volumes at final evaluation. The rate of total lateral ventricular enlargement did not differ significantly by patient sex, ventricular size at initial evaluation, age, or degree of cognitive impairment as measured by Mini Mental State Examination scores. However, in the six DAT patients initially found to have isolated memory impairment, the rate of ventricular enlargement during the period of isolated memory impairment was significantly less than the rate of ventricular enlargement after the onset of nonmemory cognitive impairment. The diagnostic power of total lateral ventricular measures made from two CTs separated by 1 year and obtained early in the course of the illness, however, was only 0.33. We conclude that the total lateral ventricular enlargement accompanying DAT is due to continuous, pathologic cell loss, significantly greater than cell loss due to the healthy aging process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407588 TI - Analysis of the DNA duplication 17p11.2 in Charcot-Marie-Tooth neuropathy type 1 pedigrees: additional evidence for a third autosomal CMT1 locus. AB - We have restudied two clinically typical Charcot-Marie-Tooth neuropathy type 1 (CMT1; also known as hereditary motor and sensory neuropathy 1) pedigrees that were previously reported to be unlinked to the regions of proximal chromosome 1q and chromosome 17p by multipoint linkage analyses. In these two pedigrees, there is no evidence for linkage to additional DNA markers that flank and span the CMT1A locus on chromosome 17p11.2, and a duplication associated with CMT1A is not present in these pedigrees. These findings confirm that the CMT1 locus in these two pedigrees does not map to chromosome 17p11.2 or 1q, and provide further evidence for the existence of a third autosomal locus for CMT1. PMID- 1407589 TI - The effect of exercise on levodopa absorption. AB - We studied the effect of exercise using cycle ergometry on levodopa absorption in ten patients with Parkinson's disease. Oral levodopa was administered during exercise and at rest on separate days. Exercise delayed levodopa absorption in five patients, increased it in three, and did not influence it in two. We conclude that exercise can either increase or decrease levodopa absorption. PMID- 1407590 TI - Homozygosity for the transthyretin-Met30 gene in three Japanese siblings with type I familial amyloidotic polyneuropathy. AB - We report the cases of three siblings homozygous for a mutated transthyretin (TTR) gene that causes type I familial amyloidotic polyneuropathy (FAP), in whom we made the diagnosis by identifying both the mutated TTR gene and a variant TTR in their sera. Their serum levels for the variant TTR are twice those of patients heterozygous for the gene, but two have late-onset FAP and the third is an elderly asymptomatic carrier. TTR abnormality is a necessary condition for the development of FAP, but there may be other factors that retard or prevent its clinical development. PMID- 1407591 TI - Research initiatives on Machado-Joseph disease: National Institute of Neurological Disorders and Stroke Workshop summary. PMID- 1407592 TI - Hallucinatory vision of a familiar face following right temporal hemorrhage. PMID- 1407593 TI - PET assessment defended. PMID- 1407595 TI - Pick's disease. PMID- 1407594 TI - Intravenous immunoglobulin. PMID- 1407596 TI - Theophylline and seizures. PMID- 1407597 TI - Epilepsy due to neurocysticercosis. PMID- 1407598 TI - Neuropsychological tests in HIV. PMID- 1407599 TI - Baclofen for spasticity. PMID- 1407600 TI - Transverse myelopathy. PMID- 1407601 TI - Franz Gall. PMID- 1407602 TI - Robert Boyle. PMID- 1407603 TI - Hemodynamic and electrophysiological evaluation following extracranial/intracranial bypass surgery. AB - We examined 50 patients with an extracranial/intracranial bypass using transcranial Doppler blood flow mapping, somatosensory evoked potentials, and computer-assisted EEG analysis. The investigation was supplemented by temporary compression of the extracranial supplying vessel. Transcranial Doppler sonography revealed in addition to 4 patients with nonpatent anastomoses, a bypass-mediated retrograde flow in the ipsilateral middle cerebral artery beyond a depth of 40 mm in the majority of patients. In 9 patients, retrograde flow could be demonstrated in the whole proximal (M1) MCA segment. The precommunicating segment of the anterior cerebral artery (A1) could be reliably insonated in all but 5 patients. Bypass-compression dependent alterations in the SSEP and in EEG analysis were only observed in a small number of patients. Transcranial Doppler sonography, with the aid of the flow mapping system, appears therefore, to be a reliable and repeatedly performable noninvasive technique for the assessment of intracranial hemodynamics following bypass surgery. PMID- 1407604 TI - Dermoid and epidermoid cysts of the midline in the posterior cranial fossa. AB - Clinical features and surgical outcome of 16 patients with dermoid or epidermoid cysts on the midline of the posterior cranial fossa are compared. Salient points in the comparison are the younger age, presence of associated malformations and better prognosis of dermoid cyst. PMID- 1407605 TI - Spontaneous intracerebral hemorrhage. AB - We report on 146 patients with spontaneous intracerebral hemorrhage treated in the period between 1984 and 1988. The aim of this retrospective study was to point out factors for operative respectively conservative treatment. Looking for etiology, age, unconsciousness, localization and extension of hematoma as well as bleeding into the ventricles our results showed that patients over 70 years of age and/or in coma III and IV (Brussels Coma Scale) have a bad prognosis as well as patients with intraventricular bleeding. Patients seem to benefit from operation if hematoma is located in the hemisphere or cerebellar and the extension ranges from 3 to 5 cm. PMID- 1407606 TI - Malignant tumors of the anterior cranial skull base. AB - Malignant tumors of the anterior cranial skull base are still a challenge for radical surgical treatment. Several different techniques and approaches have been developed over the years and the results, with mortality rates over 50%, are still not encouraging. Here we present our results of an interdisciplinary, one stage, neurohino transfronto-transbasal surgical approach in twelve patients with such tumors. The long-term survival rate in our patients is now 83% with a mean postoperative follow-up of 19.3 months. Two patients died due to early recurrencies and metastasis after 10 and 13 months after initial treatment and postoperative irradiation. Another five patients with a follow-up of 34.2 months have had tumor recurrencies diagnosed at 19.5 months postoperatively. These patients have survived their recurrent tumor for 14.7 months. Five patients, 41% of the whole group, have been living without evidence of tumor recurrence for between 2 and 35 months. PMID- 1407607 TI - The use of Nd:YAG laser in pituitary surgery and evaluation of visual function by visual evoked potential (VEP). AB - Surgery of pituitary tumors has been improved by microneurosurgical methods. However, despite improvements in surgical results, pituitary tumors still continue to represent a problem and, therefore, prompt a search for new surgical techniques. Since Nd:YAG laser energy penetrates the target tissue more deeply than other instruments, its use in the para- and suprasellar region should be considered. It is well known that Visual Evoked Potential (VEP) is a sensitive and objective method for the valuation of compressive or destructive lesions in or around the optic nerve. Visual function correlates with the latency and amplitude of P100 wave in VEP. We used the Nd:YAG laser in 50 transsphenoidal operations of pituitary adenomas. Postoperative effects of the laser on visual function was evaluated by conventional neurophthalmological tests as well as VEP and was compared with preoperative values. Following surgery using Nd:YAG laser, both conventional neurophthalmological tests and VEP values improved due to decompression of optic nerves by tumor removal. In this study, we also examined anterior lobe functions and found that Nd:YAG laser does not affect these functions. Our study shows that Nd:YAG laser has no harmful effects and seems to be very helpful especially for surgery for invading hormone-active adenomas. PMID- 1407608 TI - Traumatic brain edema induced by ventricular puncture. A study by magnetic resonance imaging. AB - Magnetic resonance imaging demonstrates after ventricular catheterization a focal brain hypersignal corresponding to a parenchymal edema along the drain track. In the course of our daily clinical activity, this hypersignal extension seemed more pronounced when catheterizing the frontal area than the junctional parieto temporo-occipital parenchyma (or trigonal area). In order to confirm this impression, we prospectively studied ten consecutive patients with normal pressure hydrocephalus in whom both of these brain regions were successively catheterized first by a frontal puncture for intracranial pressure monitoring and then by a trigonal one for a ventricular shunt. Each patient was evaluated by serial magnetic resonance imaging. The extension of the hypersignal induced by both catheterizations was estimated on a scale of five grades (0 to 4) of hypersignal extension. A statistically significant more important hypersignal extension was demonstrated at the level of frontal area when compared to the trigonal one. We discuss the likely underlying mechanisms of this phenomenon. PMID- 1407609 TI - Neoplastic and reactive human astrocytes express interleukin-8 gene. AB - Expression of lymphokine genes in the human astroglial cell lineage was studied. Primers for 9 different human lymphokines, from IL-1 alpha to IL-8, were used to analyze RNA transcripts in 5 cultured human astrocytoma cell lines and fresh brain specimens by PCR. mRNA transcripts for IL-8 were detected in all neuroglial cells. In addition to the cultured cells, we examined IL-8 gene expression within human malignant astrocytoma, peritumoral brain and autopsied normal brains. The result shows that tumor and cells of the surrounding reactive lesion express IL-8 genes, but it is not expressed in normal brains. Next, the concentration of IL-8 in supernatants of cultured cells was measured quantitatively by a solid phase ELISA assay. IL-8 activity was produced constitutively in all astrocytomas and increased markedly upon stimulation with IL-1 beta or TNF alpha, in both a time- and dose-dependent fashion. From these results, it is suspected that astroglial cell-derived IL-8 may take part in neutrophil-mediated inflammation which accompanies infection, degeneration and malignancy in the brain. PMID- 1407610 TI - The frontoorbital advancement--on the use of 3D-CT and the miniplate osteosynthesis. AB - Between 1987 and 1991 we performed a unilateral or bilateral frontoorbital advancement to correct trigono- or plagiocephaly in 10 children: Three dimensional CT provides an exact basis for operation planning. Titanium miniplates allow an already primarily rather stable osteosynthesis. The best time for this intervention is the end of the third month of life. PMID- 1407611 TI - Pneumosinus dilatans after prolonged cerebrospinal fluid shunting in young adults with cerebral hemiatrophy. A report of two cases and review of the literature. AB - Pneumosinus dilatans is a generalized or partial enlargement of the paranasal sinuses containing only air. Pneumosinus dilatans occurs as an idiopathic disorder as well as in association with other disorders, including cerebral hemiatrophy. We report two cases of patients with congenital cerebral hemiatrophy who developed juvenile pneumosinus dilatans of the frontal, ethmoidal, and sphenoidal sinus. The hydrocephalus of both patients was treated by prolonged cerebrospinal fluid shunting. The development of hyperpneumatization of the paranasal sinuses was proved by plain radiographs and CT. Previous reports of pneumosinus dilatans are reviewed, and the effect of prolonged cerebrospinal fluid shunting in our cases is discussed. Cerebrospinal fluid shunting during the period of physiological pneumatization of paranasal sinuses might have increased hyperpneumatization. PMID- 1407612 TI - Primary Ewing's sarcoma of the skull: follow-up with bone scanning. AB - The authors report and discuss an extremely rare case of primary Ewing's sarcoma originating in the flat bones of the skull. The case was followed up by serial bone scanning during the postoperative period. A subclinical recurrence was detected as a focus at the original site 2.5 years after the first operation. Following a second operation and adjuvant chemotherapy the patient is still asymptomatic. PMID- 1407613 TI - Metastasis of a renal carcinoma to a cerebellar haemangioblastoma in a case of von Hippel-Lindau disease. AB - A patient with Von Hippel-Lindau disease had a long-standing cerebellar cyst which recurred for the fifth time. At operation there was evidence of a renal carcinoma metastasis in the wall of the cyst which was probably a haemangioblastoma. PMID- 1407614 TI - [Noninvasive evaluation of cardiac index and ejection fraction in ischemic heart disease. Comparison of thoracic bioimpedance, thermodilution and cineventriculography]. AB - Aim of the study was to verify the reliability of thoracic bioimpedance cardiography (TEB) in detection, non-invasively, cardiac index (IC) and ejection fraction (FE), compared to simultaneous evaluation by invasive thermodilution (TD) in 39 patients with acute myocardial infarction in Killip class I-II (group I), and by cineventriculography (CVG) in 26 patients with chronic coronary artery disease in NYHA class I-II (group II). In order to define the reproducibility of TEB values, in the latter patients, the above mentioned parameters were evaluated 6 times more, running the first evaluation. The statistical analysis was performed by the linear regression test and the Student's "t" test and by the test of variance for the reproducibility evaluation. Results (mean +/- SD) were as follows: group I: TEB-IC 2.89 +/- 0.63; TD-IC 2.83 +/- 0.56 (1/min/m2); r = 0.68; p < 0.01. Group II: TEB-IC 2.88 +/- 0.71; CVG-IC 3.48 +/- 0.66; r = 0.77; p < 0.001; TEB-FE 57.7 +/- 6.8%; CVG-FE 58.1 +/- 13.7%; r = 0.40; p = ns. Results of the reproducibility referred to the 6 measurements (mean +/- SD) were the follows: TEB-IC (1/min/m2) (1) 2.83 +/- 0.76; (2) 2.85 +/- 0.73; (3) 2.8 +/- 0.79; (4) 2.83 +/- 0.71; (5) 2.87 +/- 0.81; (6) 2.88 +/- 0.8, p = ns, the variability was assesses within +/- 9.3%. TEB-FE (%): (1) 56.7 +/- 6.2; (2) 55.8 +/- 5; (3) 57.1 +/- 5.5; (4) 56.1 +/- 6.1; (5) 55.4 +/- 5.8; (6) 57.3 +/- 6.3, p = ns; the variability was assessed within +/- 9.1%. The analysis of the results showed a good correlation in the IC detection among TEB and the compared techniques, conversely TEB evaluation of FE appear of poor values in this kind of patients. Relatively to the results of the reproducibility this unquestionable characteristic of TEB was demonstrated. PMID- 1407615 TI - [Hemostatic parameters in patients with type IIA and IV hyperlipoproteinemia]. AB - In order to assess the interrelationships between the lipemic and the haemostatic balance the Authors studied the behaviour of some thrombotic markers in hyperlipemic subjects. The series consists of 35 subjects (15 m, 20 f, mean age 56 +/- 9 years) suffering from primary polygenic hyperlipoproteinemia of type IIA (23 cases) and type IV (12 cases) (cholesterol and triglyceride values exceeding respectively 250 and 180 mg%); 38 control subjects matched for sex, age and body weight were also examined; all the subjects were without hepato-renal and endocrine-metabolic disorders as well as without clinical signs of arteriosclerotic vasculopathy. For each subject the Authors performed the assay of the fasting plasma levels of total cholesterol (TC), triglycerides (TG) (enzymatic methods), fibrinogen (F) (coagulometric method), factor VII (coagulometric method) (F VII), antithrombin III (AT III) (chromogenic method), tissue activator of plasminogen (tPA), beta-thromboglobulin (BTG) and D-dimer (D D) (ELISA method). The type IIA hypercholesterolemic subjects showed a not significant trend in a thrombophilic sense of the markers (increase of F, F VII, BTG and D-D, decrease of AT III); the type IV hypertriglyceridemic subjects exhibited a significant (0.05) increase of factor VII, BTG and D-D compared to the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1407616 TI - [Echocardiographic changes in patients with polycystic nephropathy]. AB - We have studied with the echocardiography M-Mode, 2-D, Doppler three groups of 15 subjects for testing the presence of cardiac abnormalities probably related to primary collagen defect in patients with autosomal dominant polycystic kidney disease (ADPKD) The first group was made up of patients with ADPKD and normal renal function, the second of patients with ADPKD in hemodialysis (HD), the last one of patients in HD for other renal disease. In the first group we found no cardiovascular abnormalities while we found an increased incidence of valvular disease (p = 0.016) in patients with ADPKD in HD and an increased incidence in valvular disease (p = 0.016) and left atrial dilatation (p = 0.006) in patients in HD for different renal disease. When we estimated the cases on the ground of dialytic age uncorrelated with the initial renal disease, only the incidence of valvular calcifications was increased in patients on HD more than 3 years (p = 0.034). In our group of patients the echocardiographic abnormalities seem to be related more to uremic cardiomyopathy even if we cannot deny the existence of primary cardiac disease in patients with ADPKD. PMID- 1407617 TI - [Antibiotic pretreatment of heart valve prostheses]. AB - Bacterial endocarditis on cardiac valvular prosthesis is still a frequent and dangerous complication: septicemia, embolism, valvular dysfunction and mortality. To prevent these complications, intraoperative treatment of prosthesis, by immersion in antibiotic solution, was performed in 1262 patients. The postoperative results have been compared with results of a nontreated group. The incidence of endocarditis in the treated group was 1.3%, in non-treated cases 5.45%. The cases of early endocarditis, was 0.08% of total cases of complications in the treated patients group; and 4.54% in the nontreated patient group. This study's results, confirm the utility of valvular prosthesis antibiotic treatment in cardiac surgery. PMID- 1407618 TI - [Abnormalities of the sensing function. Further contributions to the current classification]. AB - With systemic unipolar pacemaker control by chest wall stimulation and interference we have obtained further data of the sensing function in more the 5000 clinical controls. A better classification of abnormal sensing function is important for a full electrocardiographic interpretation. We have established that the oversensing is always a primary evident or concealed phenomenon. Undersensing is a primary or secondary phenomenon provoked by a concealed oversensing in refractory period. PMID- 1407619 TI - [Inter-electrode distance and atrial sensing. Our experience with atrial-guided pacing (VDD) in the biennium 1990-1991]. AB - We implanted 47 Phymos VDD pacemakers (53.7% for complete atrioventricular block 42.57% for symptomatic lower heart block) in the 1990-91 period. In this series of cases with EDE 830-830S leads by means Holter technique we evaluated the atrial trigger. A high percentage of atrial sensing (97.8%) was found with 11 cm leads. The right atrial motion study is realized to explain the atrial sensing with floating leads. PMID- 1407620 TI - [Iatrogenic torsade de pointes induced by thioridazine]. AB - Torsade de pointes is a form of polymorphous ventricular tachycardia in which the polarity of the QRS complex exhibits phasic alterations in both axis. Traditionally, torsade de pointes has been described in association with a congenital or acquired (including drug and metabolic) causes of QT prolongation. Clinical outcomes range from asymptomatic, self-terminating arrhythmias to ventricular fibrillation resulting in cardiac arrest. For the treatment of torsade de pointes, the conventional antiarrhythmic drugs cannot be relied on, cardiac pacing should be instituted as soon as possible; however, as this technique may not always be immediately available, isoproterenol infusion may be the first-choice treatment. Potassium and magnesium repletion appear to be essential in abolishing drug-induced torsade de pointes. This report describes a case of thioridazine-induced torsade de pointes treated efficaciously with magnesium sulphate and overdrive right ventricular pacing. PMID- 1407622 TI - [Diagnostic "gold standard" in cerebrovascular insufficiency. Comparison of angiographic and ultrasonic imaging]. AB - The Authors consider the complex diagnostic problems of cerebrovascular disorders, with particular concern to angiography and echography. After a complete analysis of different aspects of angiographic and echographic lesions, considering their experience, they identify chances and limits of the two methods, they draw the conclusion that each of the two techniques has a proper role, and only a correct correlation between them can depict correctly the pathologic lesions. PMID- 1407621 TI - [Gallbladder calculi: what therapy of choice?]. AB - The Authors have analyzed all different methods for the treatment of gallbladder stones which are performed today: the non invasive treatment of the gallstones (oral dissolution therapy and the extracorporeal shockwave lithotripsy), the minimally invasive procedures (contact dissolution therapy and the cholecystolithotomy) and at the end the new surgical techniques (the "minicholecystectomy" and the laparoscopic cholecystectomy). From this study and their experience, based upon 1346 standard cholecystectomy, the Authors have reached the following conclusions: 1) the cholecystectomy remains the only definitive therapy for the gallbladder stones and it is the gold standard to which must be compared the other alternative therapies; 2) the laparoscopic cholecystectomy, even though introduced recently, would become the only method used for cholecystectomy. PMID- 1407623 TI - [Tumor markers in colorectal cancer]. AB - Over the past ten years numerous studies have been carried out to identify tumour markers able to diagnose cancer of the digestive tract. The paper reports the combined use of some markers (CEA, TPA, GICA, CA 125) in patients with carcinoma of the colon-rectum. The Authors conclude that although these markers are of little use, especially in association, in the early diagnosis of disease, it is very important to utilise these markers to monitor patients following surgical, chemotherapeutic or radiotherapeutic treatment. PMID- 1407624 TI - [Role of endoscopy in the diagnosis and follow-up of bleeding lesions of the colon]. AB - Considering the results of the centre of colonoscopy we can draw some considerations about the irreplaceable role of endoscopy in the diagnosis of bleeding colonic lesions and about its greater security in comparison with the traditional radiologic exam, about its possibilities to be sometimes resolutive even for the therapy and about its great importance in the follow-up of patients treated for lesions of this kind. PMID- 1407626 TI - [Squamous papillomas of the esophagus]. AB - The paper reports 14 cases of squamous papilloma of the esophagus which were removed using an endoscopic method: this is a comparatively rare benign pathology of which an increasing number of cases have been recently observed. Endoscopic controls were carried out in all cases and the results of the follow-up are reported. PMID- 1407625 TI - [Acute enterorrhagia. A diagnostic-therapeutic approach]. AB - The Authors report their experience in cases of severe lower intestinal bleeding. On the basis of personal data and previously reported results, endoscopy is shown to be the primary and sometimes essential method, especially in the case of colo rectal bleeding, both in terms of its diagnostic precision and possible therapeutic uses. This technique was used to treat all emergency cases, obtaining a diagnostic resolution in 85.6% and hemostasis and/or the concomitant removal of the lesion in 52.3% of cases. PMID- 1407627 TI - [Complications of hepatic hydatidosis]. AB - Fifty cases of complicated hydatid cyst of the liver on a total of 250 cases of hydatid cyst observed were analyzed. The Authors describe the several complications observed (compression, infection, rupture into biliary tract or into the thorax or into the peritoneal cavity, the diagnostic and therapeutic procedures. Total mortality was about 7.6% (3 cases) 2 patient died for intraperitoneal rupture and one for rupture in the biliary tract. Surgical treatment should be as radical as possible performing total or subtotal pericystectomy, hepatic resection is reserved to selected cases. Drainage by Kehr tube of biliary tract is necessary of rupture of the cyst in the biliary tract, while we limit the indication for a papillostomy to the sphincter duct stenosis. PMID- 1407628 TI - [Aneurysms of the peripheral arteries]. AB - The Authors examine aetiological, pathological, and clinical patterns of the peripheric aneurysms and emphasize the frequency with which an aneurysm, even when asymptomatic, can complicate and cause acute ischaemia of a limb with high risk of amputation. They present their personal experience of ten operated cases, some of choice, others in emergency, and report the immediate and late results. PMID- 1407629 TI - [Acute thrombosis of the lower limbs: choice of treatment?]. AB - The paper reports the Authors' experience of treating acute thrombotic-type ischemia of the lower limbs. It analyses the results obtained in 105 patients treated either using vascular reconstruction, loco-regional fibrinolytic therapy, or simple thrombectomy. Statistical analysis reveals a marked difference between reconstructive surgery and simple thrombectomy, whereas fibrinolysis was found to be a useful but limited method used only in patients with pallid ischemia and in circulatory compensation. In conclusion, the Authors sustain that an aggressive type approach is currently the most reliable method to be used in all cases in which the patient's general and local conditions permit. PMID- 1407630 TI - [Mechanical and antibiotic preparation and infections in colorectal surgery. Comparison of 2 methods of orthograde lavage]. AB - The efficacy of two methods of orthograde lavage preparation in elective colorectal surgery was tested in 133 consecutive patients: the results obtained with whole gut irrigation (50 patients, group A) were compared with the results of oral lavage solution (83 patients, group B). All patients received a parenteral association of antibodies (clindamycin in combination with a broad spectrum antibiotic, mainly II or III generation cephalosporins). Bacterial cultures were carried out at the end of the lavage in the rectal effluent (no statistically significant differences between the two groups) and in the intraoperative aspirate from the colon (the bacterial concentration was higher in group B). The total number of infections was 12 (9%), with 6 (12%) in group A and 6 (7.2%) in group B. The infectious complications involved perineal wound in 9 cases (in 2 patients in combination with abdominal wound infection), abdominal drainage in 2 and abdominal wound in 1. The type of broad spectrum antibiotic did not affect the infection rate significantly. Perioperative and infection site bacteriological cultures grew the same type of organism only in one case. The surgeons' judgement of the adequacy of the cleansing favored whole gut irrigation, although the results of the study revealed that both methods were safe and provided equally adequate bowel cleansing. PMID- 1407631 TI - [Surgical day hospital: technical possibilities and organizational model]. AB - The Authors propose an organizational model for a surgical day hospital program, which is being used for a pilot day surgery unit in the I Department of Surgery of the Rome University "La Sapienza". The program requires little capital investment, as it is closely linked, geographically and administratively, to the main surgical unit, and uses the present staff, facilities and support services. The model is based on a computerized LAN (Local Area Network), providing fast recording, scheduling, management and trannsfer of medical data for each patient. The present situation is reported in detail. Data from the authors' outpatient department for 1988, have been recorded and elaborated. The results show a low use of surgical day care, limited to minor surgical procedures, and with not a single operation performed under general anesthesia. The authors hope to see a growth in the use of day surgery and a more selective use of inpatient care. PMID- 1407632 TI - [Association of biliary calculosis and portal cavernomatosis]. AB - This paper reports the case of a woman, who underwent surgery because of cholelithiasis, with intraoperative finding of prehepatic portal hypertension from portal vein thrombosis ("portal cavernoma") with healthy liver, later confirmed by angiographic studies. This rare pathologic association carries a higher risk of major operative complications; therefore the Authors agree with the general belief that, for these cases, biliary tract surgery should be as simple and safe as possible. In the case of preoperative diagnosis of biliary disease associated with portal cavernoma, should a surgical approach on the biliary tract be required, we agree on the advisability of performing a shunting procedure before any kind of biliary surgery. In case of variceal bleeding endoscopic sclerotherapy will be the first choice; surgical procedures (shunting) should be seen as a second choice in case of rebleeding after sclerotherapy. PMID- 1407633 TI - [The Roux loop syndrome: a postgastrectomy syndrome. Description of 2 clinical cases]. AB - The Roux-En-Y operation has been used to control enterogastric reflux occurring after previous distal gastric resection and it has been used extensively in the treatment of alkaline reflux. Recently a postgastrectomy syndrome characterized by chronic abdominal pain, persistent nausea and vomiting that is exacerbated by eating and that develops after the Roux-En-Y operation has been described. It has therefore been postulated that the Roux-En-Y limb acts as a functional obstruction and causes the symptoms. PMID- 1407634 TI - [Polycystic retroperitoneal leiomyosarcoma. A clinical and anatomo-pathological contribution]. AB - The Authors report an unusual case of retroperitoneal leiomyosarcoma, multicystic, resembling an ovarian cystoma in a patient with simultaneous subclavian-axillary thrombosis. They analyze anatomo-pathological and clinical aspects of this kind of tumor and underline the possible errors they themselves faced. To they come to the conclusion that a careful diagnostic iter of this kind of tumor must be carried out and that the surgical approach must be radical. PMID- 1407635 TI - [A case of extrarenal angiomyolipoma with intestinal localization]. AB - The Authors present a case of extrarenal angiomyolipoma. The tumor arose from the pericolonic fat of the sigmoid colon and, increasing in size, caused intestinal obstruction by extrinsic lesion. Extrarenal angiomyolipoma is extremely rare and to our knowledge this is the first reported case arising from the colonic wall. PMID- 1407636 TI - [From laparotomy to pelviscopy. A new trend]. AB - Our pelviscopic operative series from 1986 to June 1991 is reported. Nowadays our group performs 70% of female genital benign lesions by the pelviscopic technique. Infect laparotomy has been abandoned in case of benign ovarian cyst while the pelviscopic myomectomy rate is about 69%. Our results show that this kind of management is safe and also undeniable advantages such as morbidity reduction, shorter hospital stay, less social cost, quick return to work and renewing of the method make the indications more and more every day. PMID- 1407637 TI - [Spontaneous abortion. Epidemiologic considerations]. AB - The authors report on the incidence of spontaneous abortion, the commonest complication of the pregnancy. The period examined is from March 1989 and March 1991, in the obstetrical division of University of L'Aquila. The incidence and association between maternal age, malformations, parity, maternal cigarette smoking and alcohol are reported. PMID- 1407638 TI - [Identification of growth hormone in human embryos and fetuses]. AB - The authors report a study on 10 human fetuses aged between 9 and 16 weeks of gestation. A PAP technique (peroxidase-anti-peroxidase) was used to identify the time and place of growth hormone appearance. Data obtained show intense positivity for chondrocytes, obleoblasts and perichrondrium. Hepatocytes were also found to be positive. These results suggest that GH plays an important role in a number of tissues in which it conditions maturation and development. PMID- 1407639 TI - [Predictive factors of infantile cerebral lesions during pregnancy and labor]. AB - The risks connected with children's cerebral lesions are examined by means of two different surveys related to a retrospective study over a period of about 10 years. One of these surveys is clinical and is based in the obstetric case history of children carrying psychomotor handicaps. The other survey is instrumental and concerns 100 cases of pathologic cardiotocography during labour associated with fetal suffering. The results of border surveys are discusses. For the assessment of the obstetric risk the sum of the pathologic conditions that emerged during pregnancy and delivery have to be taken into consideration. Cardiotocography is still a fundamental diagnostic examination to recognise the suffering fetus and the data collected real a close association between cardiotocography diagnosis and the conditions of the baby at the birth. PMID- 1407640 TI - [Prolapse of the vaginal vault after hysterectomy. A simple method for "anterior" abdominal correction]. PMID- 1407641 TI - [Prevention of thrombotic complications in postoperative gynecology]. PMID- 1407642 TI - [Prophylactic use of cefotetan in gynecologic surgery]. AB - The efficacy of prophylactic treatment with systemic antibiotics in laparotomic gynecologic surgery is well established. Lately, short-term schemes have been preferred in surgical prophylaxis for different reasons. First of all, experimental data demonstrated that the efficacy of an antibiotic is maximal when it reaches active tissue concentrations at the time of bacterial contamination. In addition with the availability of new, long-acting antibiotics, a long period of time around the operations was possibly covered. The effectiveness of a single preoperative 2 gm dose of Cefotetan was compared with a traditional treatment of 3 gm daily of Cefazolin for one week following surgery in 86 women undergoing laparotomic gynecologic surgery for benign pathology. Our results confirm that preoperative treatment with Cefotetan is able to prevent infectious disease such as 3 gm of Cefazolin per day for one week. Thus, Cefotetan can be used for this type of prophylaxis considering its broad spectrum of action and pharmacokinetic properties. PMID- 1407643 TI - [THe use of leuprolide in endometrial glandular hyperplasia]. AB - Endometrial hyperplasia is a very frequent pathology during menopause and involves the risk of the malignant transformation of lesions and the onset of anemia due to concomitant clinical phenomena. Standard medical treatments often involve major collateral effects which impede their long-term use. In an attempt to avoid radical surgery for many women or the use of other invasive techniques, this paper proposes the use of Leuprolide acetate which was used to treat 30 patients with histologically confirmed symptoms of endometrial hyperplasia without atypia. This controlled-session LHRH analog was administered using an intramuscular route every 30 days for 6 months. Hysteroscopic and histological controls were carried out 30 days after the last treatment and showed the resolution of histological and clinical symptoms; this was confirmed after 3 months. Fibroma, which are the most frequently associated pathology, were considerably reduced. PMID- 1407644 TI - [Report of a case of autoimmune thrombocytopenic purpura in pregnancy]. AB - A clinical report concerning a severe idiopathic thrombocytopenia during pregnancy (minimal platelet count 3000/mm3 is described). Corticosteroids and immunoglobulins were administered in preparation to elective cesarean delivery. Since the platelet count not improve significantly, 3 units of platelets from a single donor were adjunctively given using diapheresis. An elective cesarean delivery was performed at 34 weeks, without further complications. The newborn weighed 2550 g and the postnatal course was uneventful. PMID- 1407645 TI - [Intravenous leiomyomatosis of the uterus. Report of a case]. AB - A clinicopathological study of a case of intravascular leiomyomatosis was performed, recalling the rarity of this pathology and the necessity of a careful follow-up. Microscopically the intravascular tumor resembles the benign leiomyoma. Authors have taken into consideration the most likely differential diagnoses: endolymphatic stromal myosis and low-grade leiomyosarcoma, they study the problem of the so-called "benign metastasizing leiomyoma" and emphasize that intravenous leiomyomatosis is frequently underdiagnosed. PMID- 1407646 TI - Protection by N-methyl-D-aspartate receptor antagonists against impairment of working memory in rats following transient cerebral ischemia. AB - A 5-min period of cerebral ischemia increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) assessed by the working memory procedure applied in a three-panel runway task. The selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist CGS 19755 (3.2 and 10 mg/kg), administered i.p. immediately after blood flow reperfusion, significantly reduced the increase in errors expected to occur 24 h after 5 min of ischemia. CGS 19755 10 mg/kg had no effect on the increase in errors when injected 6 h after ischemia. The i.p. administration of the non competitive NMDA antagonists dextrorphan 10 and 32 mg/kg and MK-801 1.0 mg/kg immediately after reperfusion decreased the increase of errors in the ischemic rats. The protective effects of NMDA antagonists suggest that the mechanism mediated by NMDA receptors during the early reperfusion phase plays a pivotal role in the postischemic impairment of working memory. PMID- 1407647 TI - Neuronal survival and neurite extension supported by astrocytes co-cultured in transwells. AB - The influence of astrocytes on the development of cerebral cortical neurons was studied in a co-culture system using transwells with chemically defined medium. Cerebral cortical neurons from 15- or 16-day-old mouse embryo were cultured in the lower wells which were separated by a porous membrane from the upper transwells where cerebral cortical astrocytes from newborn mouse were cultured. Neurons co-cultured with astrocytes for 7 days formed a network-like web and maintained a slightly better survival from 4 to 7 days. However, neurons cultured in conditioned medium obtained from astrocytes did not form any network after 7 days even though they maintained a better cell survival at 4 days. PMID- 1407648 TI - Enhancement of postsynaptic responsiveness during long-term potentiation of mossy fiber synapses in guinea pig hippocampus. AB - The primary site responsible for the long-lasting enhancement of synaptic transmission during long-term potentiation (LTP) was examined by quantal analysis of excitatory postsynaptic potentials in thin sections of the guinea pig hippocampus. With induction of LTP in mossy fiber synapses, estimated values of quantal amplitude (q) and Pascal parameters p and r were increased significantly. No increases in quantal content (m) were detected. The magnitude of increases in q was almost equal to that of LTP. These results indicate that LTP in mossy fiber synapses results from increases in responsiveness of postsynaptic neurons. PMID- 1407649 TI - Behavioral and electroencephalographic effects of a serotonin receptor agonist (5 methoxy-N,N-dimethyltryptamine) in a feline model of photosensitive epilepsy. AB - The effects of a serotonin (5-HT) receptor agonist, 5-methoxy-N,N dimethyltryptamine (5-MeODMT), on epileptic photosensitivity were studied in the lateral geniculate-kindled cat. 5-MeODMT at 4 mg/kg significantly suppressed photically induced myoclonus, but not paroxysmal EEG activity, at 0.5-1 h after injection. This antiepileptic effect was seen in association with the appearance of behavioral signs similar to those seen in the 5-HT syndrome. The present data provide further evidence that 5-HT plays an important role in photosensitive epilepsy, and suggest that the inhibitory effect of 5-MeODMT on photosensitivity results from its agonist action at 5-HT1 receptors. PMID- 1407650 TI - Onset of CGRP expression and its restriction to a subset of spinal motor neuron pools in the chick embryo is not affected by treatment with curare. AB - Calcitonin gene-related peptide (CGRP) is expressed in and defines a subset of motor neuron pools in the lumbar spinal cord of the chick embryo. The onset of CGRP expression in individual pools coincides with both the period of the initial innervation of the leg and the beginning of naturally occurring cell death in the lumbar motor column. Administration of neuromuscular blocking agents at this time results in a striking reduction of normal motor neuron loss. It has been reported that such treatment also results in the abolition of CGRP expression at later stages of development. In this study, we have examined the effect of curare treatment on CGRP expression in motor neurons earlier in their development. We find that, in contrast to the effects reported at later stages, inhibition of neuromuscular activity does not affect either the onset of CGRP expression or its restriction to a subset of motor neuron pools. This demonstrates that the control of the onset of CGRP expression is unlikely to be linked to processes which are regulated by neuromuscular transmission including naturally-occurring cell death. PMID- 1407651 TI - Synaptosomal plasma and mitochondrial membrane potentials during anoxia. AB - The precise mechanism by which altered oxidative metabolism impairs neuronal function is unknown. Previous indirect studies suggest that anoxia's effects on the mitochondrial membrane potentials may underlie anoxia's actions. Twenty minutes of anoxia reduced the mitochondrial membrane potential of intact synaptosomes by 38-59 mV, but diminished the plasma membrane potential by only 4 10 mV. Anoxia did not alter the response of the plasma or mitochondrial membrane potentials to K+, nor did anoxia affect the reaction of the plasma membrane potential to valinomycin. However, anoxia diminished the response of the mitochondrial membrane potential to valinomycin by 50%. Thus, partial collapse of the mitochondrial membrane potential may be an important mediator of hypoxia-or anoxia-induced changes in neuronal function. PMID- 1407652 TI - Amphetamine enhances extracellular concentrations of dopamine and acetylcholine in dorsolateral striatum and nucleus accumbens of freely moving rats. AB - The effect of two consecutive administrations of amphetamine (1.5 mg/kg, s.c.; 2 h apart) on dopamine (DA) and acetylcholine (ACh) efflux in dorsolateral striatum and nucleus accumbens was studied with in vivo microdialysis in freely moving rats. Amphetamine was found to cause a more persistent increase of extracellular DA in the dorsolateral striatum than in the nucleus accumbens. The increase in DA overflow by amphetamine was accompanied by an increase of extracellular ACh in both brain areas. The results are inconsistent with the hypothesis of an amphetamine-induced inhibitory regulation by DA on ACh overflow. PMID- 1407653 TI - Growth of axon collaterals of eclosion hormone neurons into a new release site during metamorphosis of Bombyx mori. AB - Eclosion hormone (EH) is a peptide triggering ecdysis in insects. Injection of Lucifer dye into EH producing cells in the silkworm at various stages of adult development revealed that after pupation the EH cells produced many axon collaterals to form a new neurohaemal structure in the corpora cardiaca (CC), the corpora allata and the associated nerves of the CC. The axon collaterals may serve as a major release site of EH at adult ecdysis. PMID- 1407654 TI - The immediate consequences of middle cerebral artery occlusion on GABA synthesis in mouse cortex and cerebellum. AB - The effect on gamma-aminobutyric acid (GABA) synthesis of focal ischaemia in the right cortex of the mouse was investigated by performing a right middle cerebral artery (MCA) occlusion. Synthesis of GABA was determined by measurement of the rate of GABA accumulation in tissue following injection of amino oxyacetic acid (AOAA; 30 mg/kg, i.p.). Five min following the MCA occlusion, the rate of GABA synthesis in the right (ischaemic) cortex was decreased by approximately 70% compared to either the left cortex or the right cortex of untreated controls. The basal GABA concentration was however unaffected. Four hours after the occlusion the rate of GABA synthesis was similar in the right and left cortex. The rate of GABA accumulation in the cerebellum was unchanged at both times after the right MCA occlusion compared with untreated control mice. The data suggest that there is a rapid but short lasting decrease in GABA synthesis following an ischaemic insult and it is suggested that this might be associated with the EEG spiking activity that occurs at this time. PMID- 1407655 TI - Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment. AB - Enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. We report that rats housed in an enriched environment showed improved performance in the Morris water maze and decreased spontaneous motor activity. Exposure to behavioural tests increased expression of the mRNA that encodes brain-derived neurotrophic factor in the hippocampus. This was not seen when rats subjected to impoverished housing were tested suggesting that environmental history of the animal is of importance to induce expression of brain-derived neurotrophic factor in the hippocampus that may promote neuronal changes related to learning and memory. PMID- 1407656 TI - Stress induces neuronal death in the hippocampus of castrated rats. AB - Whereas loss of CA3 neurons in the hippocampus of monkeys which died of stress ulcers suggests that some structural changes may occur, there is no direct evidence that shows stress-induced irreversible changes of neurons. When rats were orchidectomized (castrated) and stressed by restraint and immersion in water for 15 min/day for 30 days, significant loss of hippocampal CA3 and CA4 neurons was observed. Furthermore, primary cultured hippocampal neurons survived shorter when treated with corticosterone. This neuronal loss was prevented by simultaneous administration of testosterone in vivo and in vitro. These findings indicate that stress can contribute to neuronal degeneration associated with hypogonadal conditions such as aging. PMID- 1407657 TI - Interaction of vestibular and proprioceptive inputs for human self-motion perception. AB - Human perception of horizontal self(body)-motion in space was studied during various combinations of vestibular and leg-proprioceptive stimuli in the dark. During sinusoidal rotations of the trunk relative to the stationary feet (functionally synergistic combination) the perception was almost veridical over the frequency range tested (0.025-0.4 Hz). This finding suggested a dominance of the proprioceptive over the vestibular input, since the quantitative aspects of the perception (gain, phase, and detection threshold): (a) closely resembled those of the proprioceptive foot-to-trunk perception, and (b) clearly differed from those of the vestibular self-motion perception. However, when using other combinations, the self-motion perception changed in a monotonous way as a function of the two inputs, indicating that the two inputs do interact in a linear way. In a model of these findings the interaction occurs in two stages: (1) summation of a vestibular trunk-in-space signal and a (dynamically matched) proprioceptive foot-to-trunk signal yields an internal representation of foot support motion in space; (2) superposition of the latter by an almost ideal proprioceptive trunk-to-foot signal results in a representation of trunk-in-space motion (essentially proprioception-dependent and ideal when the feet are stationary). PMID- 1407658 TI - A lipoxygenase pathway of arachidonic acid metabolism mediates FMRFamide activation of a potassium current in an identified neuron of Helisoma. AB - The neuropeptide FMRFamide causes a presynaptic inhibition of neurotransmitter release from neuron B5 of Helisoma. In this study we demonstrate that one of FMRFamide's actions is to activate an outwardly rectifying potassium current. Arachidonic acid also activates an outward current in B5. The phospholipase A2 inhibitor, 4-bromophenacylbromide (BPB), and nordihydroguaiaretic acid (NDGA), an inhibitor of arachidonic acid metabolism, but not indomethacin, block FMRFamide's activation of the potassium current. Taken together these data demonstrate that one of FMRFamide's presynaptic actions is to activate a potassium current through a lipoxygenase pathway of arachidonic acid metabolism. PMID- 1407659 TI - Glutamate receptor expression in the rat retina. AB - The expression of five genes (GluR A; B; C; D; GluR 5) encoding functional subunits of glutamate receptors was investigated in the rat retina using in situ hybridization with oligonucleotide probes. All five genes are expressed in the retina. All probes label cell bodies in the ganglion cell layer as well as somata in the inner third of the inner nuclear layer (INL), where the amacrine cells are located. In addition GluR 5, B and D, and to a lesser extent also GluR A are found in the middle and outer part of the INL, where bipolar and horizontal cells reside. Different subsets of retinal neurons may thus use glutamate receptors of different subunit composition. PMID- 1407660 TI - Ultrastructural evidence for GABA-mediated disinhibitory circuits in the spinal cord of the cat. AB - The synaptic relationships between gamma-aminobutyric acid (GABA)-immunoreactive and enkephalin-immunoreactive profiles in the cat spinal cord were examined using combined pre-embedding immunoperoxidase and post-embedding immunogold electron microscopic immunocytochemistry. Although colchicine was not used, enkephalin immunoreactive somata and dendrites were detected in regions associated with nociceptive transmission, including laminae I, II, V and X. In each of these laminae, many GABA-immunoreactive terminals were found presynaptic to enkephalin immunoreactive cell bodies and dendrites. We propose that disinhibition of opioid containing neurons may be a common feature of pain-related circuits in the cat spinal cord. PMID- 1407661 TI - Neuropeptide Y messenger ribonucleic acid in the magnocellular hypothalamo neurohypophysial system of the rat is increased during osmotic stimulation. AB - In the magnocellular hypothalamo-neurohypophysial system of the rat, levels of neuropeptide Y (NPY) mRNA were investigated by in situ hybridization histochemistry both in normal and osmotically stimulated animals. As an osmotic stimulus, animals were given 340 mM NaCl to drink for 12 days. After saline treatment, there was a very marked increase in NPY mRNA in the hypothalamic magnocellular supraoptic (SON) and paraventricular (PVN) nuclei (7600% and 3200%, resp.). These data suggest that magnocellular SON and PVN neurons synthesize NPY in response to the physiological stimulus of increased plasma osmolality. PMID- 1407662 TI - Immunoreactivity of skate electrocytes towards monoclonal antibodies against human dystrophin and dystrophin-related (DMDL) protein. AB - Monoclonal antibodies against human dystrophin have been used to demonstrate the existence of a dystrophin-like protein in the electrocytes of skate electric organ. This protein is also present in skate muscle and resembles that found in Torpedo electric organ. Monoclonal antibodies against a human autosomal homologue of dystrophin (DMDL protein) did not detect a similar protein in skate or Torpedo. Immunocytochemical staining of the innervated and non-innervated faces of the electrocyte membrane was obtained using the anti-dystrophin antibodies only. PMID- 1407663 TI - Graft-derived cholinergic reinnervation of the hippocampus prevents a lasting increase of hippocampal noradrenaline concentration induced by septohippocampal damage in rats. AB - Long-Evans female rats sustained aspirative lesions of the septohippocampal pathways and, 2 weeks later, received into the dorsal hippocampus grafts prepared from the septal area (rich in cholinergic neurons; Group Sep) or from the mesencephalic raphe (poor in cholinergic neurons; Group Rap) of rat fetuses. Lesion-only (Group Les) and virtually intact (Group Sham) rats served as controls. Between 9.5 and 10.5 months after grafting surgery, we found the lesions to decrease choline acetyltransferase activity (ChAT), high affinity synaptosomal uptake of [3H]choline (HACU) and serotonin concentration ([5-HT]), as well as to increase the noradrenaline concentration ([NA]) in the dorsal hippocampus. Raphe grafts increased [5-HT] to 456% of normal, but had only weak or no effects on the other lesion-induced modifications in brain neurochemistry. Septal grafts dramatically increased ChAT activity and HACU, enhanced [5-HT], and reduced [NA] to near-normal levels. We also found a significant negative correlation between HACU and [NA] in rats with lesions, whether grafted or not. These data show that grafts providing the denervated hippocampus with a new cholinergic innervation might be able to exert inhibitory effects on the lesion induced increase of [NA]. Since such an increase is indicative of sympathetic sprouting, the finding of reduced [NA] in rats with graft-derived cholinergic reinnervation of the hippocampus is in line with the hypothesis that hippocampal cholinergic denervation plays a crucial role in the induction of sympathetic sprouting. However, our data do not allow to distinguish whether grafts rich in cholinergic neurons inhibited the sympathetic sprouting itself, or rather reduced the NA content of sprouted fibers. PMID- 1407665 TI - Recovery of distal skills after neonatal lesion of the sensorimotor cortex in the cat. AB - The cytoarchitectonic cortical areas containing the cells of origin of the pyramidal tract were unilaterally removed from kittens during the first postnatal month. After 5 months, the distal skills of these operated animals were analyzed using a food retrieving task. After an initial deficit, cats achieved the same performance in grasping and wrist movement with the limb contralateral to the lesion as with the opposite limb. The duration of the deficit was dependent on age at the time of lesion. Recovery of distal skills after neonatal lesion is discussed with regard to the low degree of maturity of the corticospinal tract in newborn cat. PMID- 1407664 TI - Evidence for the presence of excitatory A2 adenosine receptors in the rat hippocampus. AB - The A2 adenosine receptor agonist, CGS 21680 in nanomolar concentrations, reversibly increased in a concentration-dependent manner the amplitude of orthodromically-evoked population spikes recorded from the CA1 pyramidal cell layer of rat hippocampal slices. The adenosine receptor antagonist, 3,7-dimethyl l-propargylxanthine (DMPX, 10 microM), which has selectivity for A2 adenosine receptors, prevented this excitatory effect of CGS 21680. These results suggest that A2 adenosine receptors are present in the rat hippocampus and that activation of these receptors enhance hippocampal excitability. PMID- 1407666 TI - Effects of glycine antagonists on Mg(2+)- and glycine-induced [3H]N-(1-[2 thienyl]cyclohexyl)-3,4-piperidine binding. AB - We investigated the effects of glycine antagonists, 3-amino-1-hydroxy-2- pyrrolidone (HA-966), 7-chlorokynurenic acid (7-Cl-KYNA), 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX), 6,7-dichloro-3-hydroxy-2-quinoxalinecarboxylic acid (DHQXC), 6,7-dichloroquinoxaline-2,3-dione (DCQX), and 5-chloro-indole-2 carboxylic acid (5-Cl-I2CA), on Mg(2+)- and glycine-induced [3H]N-(1-[2 thienyl]cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical membranes. Except for 5-Cl-I2CA, all the glycine antagonists completely inhibited not only glycine- but also Mg(2+)-induced [3H]TCP binding in a concentration dependent manner. Out of all the glycine antagonists examined DHQXC most selectively inhibited Mg(2+)-induced [3H]TCP binding, while DCQX was the most selective for inhibiting glycine-induced [3H]TCP binding. PMID- 1407667 TI - The role of swollen astrocytes in human brain lesions after edema--an immunohistochemical study using formalin-fixed paraffin-embedded sections. AB - Swollen astrocytes (SAs) in the white matter after brain edema were immunohistochemically studied in cases with cerebral vascular events, brain tumor and protracted non-missile head injury. SAs showed a decrease in reactivity to glial fibrillary acidic protein (GFAP) and, on the other hand, were positive for laminin, an extracellular matrix glycoprotein known to be secreted by astrocytes. SAs in protracted lesions were strongly positive for both vimentin and plasma proteins including IgG, IgM, C3d and C4d. Remarkable vimentin expression in SAs, instead of GFAP, strongly suggests that SAs are not going to degenerate but are bearing up to regenerate in such circumstances. A number of vimentin-positive buttons also appeared in such protracted lesions, demonstrating disintegration of the processes of SAs. Immunohistochemical detection of plasma proteins in SAs are believed to indicate a facilitated activation in SAs to transform to macrophage like cells and to act as phagocytes. In addition, demonstration of laminin may suggest hyperactivity of laminin production in SAs after both axonal injury and concomitant edema in order to stimulate neuritic regeneration. PMID- 1407668 TI - Regional differences in the effect of N-[1-(2 benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) on extracellular dopamine levels: an in vivo microdialysis study. AB - N-[1-(2-Benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) is a phencyclidine derivative highly selective for the dopamine (DA) uptake complex. Its effect on extracellular DA levels was studied by in vivo microdialysis on freely moving rats. In the striatum, BTCP induced a dose-dependent increase in DA levels, without affecting DA metabolites. In the nucleus accumbens, a lower increase in DA was observed, but with concomitant decreases in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). These experiments show that the effects of BTCP on extracellular DA levels are significantly different on extrapyramidal and mesolimbic dopaminergic terminals. PMID- 1407669 TI - Two classes of spontaneous GABA-mediated miniature synaptic currents in cultured rat hippocampal neurons. AB - Amplitude and time course of spontaneous gamma-aminobutyric acid (GABA)-mediated miniature postsynaptic currents (MPSCs), recorded in cultured embryonic hippocampal neurons in presence of either tetrodotoxin (TTX) or increased external [Mg2+/Ca2+] ratio, revealed that they form two classes. The distribution of the most commonly recorded MPSCs was skewed both in terms of peak amplitude and rise-time (skew-MPSCs, mode: 70-120 pS). Another, less frequent class (mode: 1-3 nS) formed bell-shaped (bell-MPSCs) amplitude and rise-time distributions. MPSC initial slope did not correlate with rise time, indicating that smaller MPSCs were not electrotonically attenuated. Bell-MPSCs did not result from the integration of skew-MPSCs and both classes appeared to be composed of subunits. PMID- 1407670 TI - No psychological dependence after oral administration of morphine to rats. AB - Rats subjected to forced oral self-administration of morphine solutions without or in combination with two daily i.p. injections of morphine preferred drinking water when this was offered in addition to morphine solutions. The daily intake of morphine during the terminal phase of self-administration of morphine was 50 80 mg/kg (oral application alone) or 270 mg/kg (oral and i.p. application). Morphine treated animals showed withdrawal symptoms on administration of naloxone 1 mg/kg i.p. during the period of self-administration, but not when they had started drinking exclusively water. The tail-flick test revealed no tolerance during prolonged treatment with morphine. The results indicate that no psychological dependence developed when morphine was applied orally and regularly. PMID- 1407671 TI - Muller (glial) cells in the retina of urodeles and anurans reveal different morphology by means of freeze-fracturing. AB - Muller (glial) cells of the retina of various species of amphibia (urodeles and anurans) were investigated by means of the freeze-fracture technique. This was done because Muller cells in anamniotes were believed to differ from those in mammals in that they should lack the so-called orthogonal arrays of particles (OAP) which are a characteristic feature of Muller cells in mammalian retina. However, as we could demonstrate previously (Berg-von der Emde and Wolburg, Glia, 2 (1989) 458), fish retinal Muller cells also contain OAP in their membranes suggesting that OAP are a general marker of Muller cells in all vertebrates. As demonstrated in this study, Muller cells of urodeles (Batrachoseps attenuatus and Pleurodeles waltlii) are OAP-positive, whereas two anurans (Rana esculenta and Xenopus laevis) do not reveal any OAP in their Muller cell membranes. Under phylogenetic aspects, it appears very interesting that frogs are as yet the only vertebrate group that deviates from all other vertebrates in terms of Muller cell membrane morphology. PMID- 1407672 TI - Catecholamine histofluorescence depletion in the infarcted brain parenchyma but not in the adventitia of the occluded cerebral arteries in rats. AB - The effect of acute cerebral ischemia on the catecholamine-containing nerve fibers in the brain parenchyma and in the adventitia of the cerebral arteries was studied in the rat. Unilateral cerebral ischemia was produced with an intraluminal thread technique which does not damage the adventitia of cerebral arteries. One to three days after surgery the ischemic damage of the brain was consistently observed in the territory of the middle cerebral artery of the operated side. Depletion of catecholamine histofluorescence was observed in the infarcted brain parenchyma. However, in the adventitia of the middle cerebral arteries of the operated side, catecholamine histofluorescence remained intact. No detectable changes in fluorescence were observed in the brain parenchyma or adventitia of the cerebral arteries in the contralateral side. The results indicate that the perivascular catecholamine-containing nerve fibers are not impaired by the intraluminal occlusion of the cerebral artery in the early stage of ischemia. PMID- 1407673 TI - c-Fos protein expression in the rat subfornical organ following osmotic stimulation. AB - To examine the role of the subfornical organ (SFO) in the osmotic activation of hypothalamic neurons, the responses of the SFO to osmotic stimulation were evaluated by using c-Fos protein immunohistochemistry. Numerous c-Fos immunoreactive nuclei were found in the SFO of rats injected i.p. with hypertonic saline solution as early as 30 min after stimulation, and the effect lasted up to 3 h. Only a few c-Fos-positive cells were detected in the SFO of rats injected with isotonic saline. However, electrolytic lesions of the SFO did not prevent the osmotic activation of the hypothalamic paraventricular and supraoptic nuclei. These data suggest that the SFO and the hypothalamic magnocellular nuclei are simultaneously but separately activated by osmotic stress. PMID- 1407674 TI - Distribution of neurofibrillary tangles and senile plaques in the cerebral cortex in postencephalitic parkinsonism. AB - Postencephalitic parkinsonism is characterized neuropathologically by severe loss of pigmented neurons in the substantia nigra and the presence of high densities of neurofibrillary tangles in several brainstem structures. In 5 cases of postencephalitic parkinsonism, we observed that the neurofibrillary tangle distribution in the cerebral cortex predominated in the hippocampus and entorhinal cortex. In the prefrontal and inferior temporal cortex, neurofibrillary tangles were preferentially localized in layers II and III. This pattern contrasts with the neurofibrillary tangle distribution observed in neocortical areas of Alzheimer's disease cases, where neurofibrillary tangles are denser in layer V than in layer III. These results suggest that specific elements of the cortical circuitry might be differentially affected in postencephalitic parkinsonism as compared to Alzheimer's disease, and that cortical involvement is likely to be a common feature of this condition. PMID- 1407675 TI - Clozapine's mechanisms of action: non-dopaminergic activity rather than anatomical selectivity. AB - The mechanisms of clozapine's unusual actions were investigated in anesthetized rats. Sensory field potentials were recorded in the nucleus accumbens, striatum and somatosensory cortex. Both haloperidol and clozapine suppressed responses in the striatum and accumbens. Clozapine's but not haloperidol's subcortical actions were unaffected by dopamine depletion. In addition, the cortical effects of the two drugs differed. These data indicate that clozapine has non-dopaminergic activity but no particular specificity for limbic basal ganglia structures. While it is known that clozapine acts as a serotonergic and cholinergic antagonist, several considerations suggest that action on still another transmitter system, possibly glutamate, needs to be investigated. PMID- 1407676 TI - Spontaneous perikaryal neurofilament phosphorylation in the septofimbrial nucleus of the rat. AB - Phosphorylation of the 200 kDa neurofilament peptide NF-H usually only occurs in axons. We describe the spontaneous presence of phosphorylated NF-H in a population of small spindle-shaped neurons of the rat septofimbrial nucleus. A similar phenomenon has been observed in axotomized neurons and in human neurodegenerative diseases. Our observations, as well as previous studies by other authors, indicate that perikaryal neurofilament phosphorylation is not necessarily linked to pathological conditions. PMID- 1407677 TI - MK-801, but not anisomycin, inhibits the induction of tolerance to ischemia in the gerbil hippocampus. AB - We examined whether MK-801, an N-methyl-D-aspartate (NMDA)-receptor antagonist, or anisomycin, a reversible protein synthesis inhibitor, inhibits the induction of ischemic tolerance following preconditioning with sublethal ischemia in gerbil hippocampus. Preconditioning with 2 min of ischemia, which induced heat shock protein-72 immunoreactivity, prevented hippocampal CA1 neuronal damage following 3 min of ischemia produced 3 days later. MK-801, but not anisomycin, inhibited the induction of tolerance although the heat shock protein synthesis was reduced in both groups. The present result suggests that NMDA receptor activation, causing stress response, induces the ischemic tolerance. PMID- 1407678 TI - Brainstem projections to the medial preoptic region containing the luteinizing hormone-releasing hormone perikarya in the rat. An immunohistochemical and retrograde transport study. AB - The afferent projections to the anterior medial preoptic area (MPA) from the brainstem have been studied, in female Wistar rats, by retrograde tracing with horseradish peroxidase (HRP). The HRP was injected by iontophoresis into the preoptic region containing the luteinizing hormone-releasing hormone (LHRH) perikarya. The brain sections including the MPA were reacted with diaminobenzidine (DAB) to reveal the injection site; the LHRH cells were then immunohistochemically identified using DAB with ammonium nickel sulphate. When the injection site incorporated the LHRH cells, the brainstem sections were reacted with the DAB nickel solution to detect lysosomal HRP and then immunohistochemically processed to locate the adrenaline-synthesizing cells using DAB alone. The results confirm the brainstem projections to the MPA from the central grey matter, ventral tegmental area, subcoeruleus area, the dorsal raphe nucleus, the lateral parabrachial nucleus, the raphe pontis nucleus, the raphe obscurus nucleus, the region of the paragigantocellular nucleus and the nucleus of the solitary tract. Given the considerable evidence implicating the ascending adrenergic systems in the regulation of LHRH, we focused our attention on the afferents from the locus coeruleus, area postrema and the adrenaline-synthesizing cell groups (C1-3). The only cells which were retrogradely labelled and immunopositive for phenylethanolamine N-methyltransferase were found in C3. PMID- 1407679 TI - Release of immunoreactive enkephalinergic substances in the periaqueductal grey of the cat during fatiguing isometric contractions. AB - Antibody-coated microprobes were used to determine whether immunoreactive enkephalins were released in response to fatiguing isometric contractions of the hind-limb muscles in cats anesthetized with alpha-chloralose. Contractions were performed by stimulating the tibial nerve via a microprocessor-controlled stimulator. Microprobes were inserted into the periaqueductal grey (P 0.5-1.0 mm) prior to, during and following fatiguing contractions. During fatiguing contractions, mean arterial blood pressure increased by 76 +/- 9 mmHg above resting and recovery levels. Levels of immunoreactive enkephalins were elevated in the dorsolateral periaqueductal grey during the isometric contraction when compared to resting levels. It is possible that isometric muscle contraction causes the release of Met-enkephalin-like substances in the periaqueductal grey. PMID- 1407681 TI - Significance of nerve growth factor content levels after transient forebrain ischemia in gerbils. AB - Involvement of nerve growth factor (NGF) in the pathogenesis of delayed neuronal death (DND) of CA1 neurons in the hippocampus has been suggested. We measured regional changes in the content of tissue NGF of the hippocampus in the Mongolian gerbil after 5 min forebrain ischemia. The NGF content was found to decrease significantly in the CA3 and dentate regions by 32% two days after ischemia. By contrast in the CA1 region, the level of NGF became significantly elevated by 50% two weeks after ischemia or later. The early reduction of NGF content in the afferent area projecting to the CA1 sector might be primarily linked to the pathogenesis of DND, whereas the delayed increase within the CA1 sector might be a secondary local response mainly of reactive astroglia. PMID- 1407680 TI - The effects of cortical ablation on d-amphetamine-induced changes in striatal dopamine turnover and ascorbic acid catabolism in the rat. AB - Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA) and dehydroascorbic acid (DHAA) levels were determined by HPLC in the striatal synaptosomal fraction and in the whole striatum of rats, whose fronto-parietal cortex had been bilaterally ablated, after a single injection of d-amphetamine (2.0 mg/kg i.p.). d-Amphetamine significantly increased the DHAA/AA ratio in unoperated and sham-operated rats, but failed to increase it in ablated rats, as compared to pertinent saline-treated groups. In the synaptosomal fraction, d amphetamine significantly decreased the DHAA/AA ratio in unoperated, sham operated and ablated rats. d-Amphetamine significantly decreased the DOPAC/DA ratio in the whole striatum and significantly increased it in the striatal synaptosomal fraction in all experimental groups. Cortical ablation greatly increased d-amphetamine-induced motor hyperactivity. We conclude that the d amphetamine-induced increase in AA striatal oxidation requires integrity of the cortico-striatal glutamatergic pathways. Further, AA oxidation occurs in the extracellular space. The cortico-striatal glutamatergic pathways exert an inhibitory modulation on d-amphetamine behavioral effects. PMID- 1407682 TI - The changing axonal distribution in white muscle of the developing catfish, Ictalurus nebulosus (Lesueur). AB - The development of the peripheral innervation pattern of the axial white muscle fibres of the brown bullhead, Ictalurus nebulosus (Lesueur), was investigated utilizing silver impregnation. In the younger fish examined, axons were observed to run along the myoseptum and into the body of the myotome. With development, axons were gradually restricted to the myoseptal ends as is the situation in adult bullheads. Possible mechanisms for elimination of the superfluous axons observed in the white muscle of the developing brown bullhead are discussed. PMID- 1407683 TI - Initial observations on the distribution of cannabinoid receptor binding sites in the human adult basal ganglia using autoradiography. AB - The distribution of cannabinoid receptor binding sites has been studied in the basal ganglia of 3 human adults using the synthetic cannabinoid agonist [3H]CP55,940 and autoradiography. The [3H]CP55,940-specific labeling was found in the caudate, putamen, accumbens, substantia nigra pars reticulata, and globus pallidus. The binding was consistently higher in the medial over the lateral part of the globus pallidus. PMID- 1407684 TI - Eating and drinking cause increased dopamine release in the nucleus accumbens and ventral tegmental area in the rat: measurement by in vivo microdialysis. AB - Dopamine (DA) release was simultaneously monitored in the nucleus accumbens (NAC) and ventral tegmental area (VTA) of conscious rats using in vivo microdialysis. During dialysis perfusion, rats were allowed access to food or water for 20 min following a 36 h food and water deprivation period. DA release increased significantly in the NAC and VTA in response to eating and drinking. The increases in both regions continued until 20-60 min after the end of the feeding or drinking session. These results show that the mesolimbic DA pathway is activated in response to ingestive behavior, and that DA release occurs in the cell body (A10) region as well as in the mesolimbic DA nerve terminals. PMID- 1407685 TI - Activation of hippocampal metabotropic excitatory amino acid receptors leads to seizures and neuronal damage. AB - A role for ionotropic (NMDA, AMPA, and kainate) excitatory amino acid (EAA) receptors in seizure and seizure-related brain damage is well documented. To study the possible role of metabotropic (G-protein linked) EAA receptors in this regard, a highly selective metabotropic EAA agonist was injected into the hippocampus of halothane-anesthetized rats. This resulted in delayed-onset seizures and selective hippocampal neuronal damage that was indirectly mediated by NMDA receptors. This provides direct evidence for a novel role of metabotropic EAA receptors in the etiology of seizures and neuronal damage. PMID- 1407686 TI - Intrathecal midazolam versus intrathecal morphine in orofacial nociception: an experimental study in rats. AB - The antinociceptive properties of intrathecal midazolam (15 and 30 micrograms) and intrathecal morphine (30 micrograms) were compared using an adaptation of the formalin test to the orofacial region in rats. Both midazolam and morphine were effective in reducing the nociceptive response of the second phase of this biphasic pain test. Only midazolam (30 micrograms) reduced also the first phase. These results confirm the existence of analgesic properties of midazolam in the case of long-lasting pain. PMID- 1407687 TI - Potentiation by cyclooxygenase inhibitors of the release of catecholamines from the rabbit carotid body and its reversal by prostaglandin E2. AB - Salicylates, at the high therapeutic doses used in the treatment of rheumatoid arthritis, produce an increase in ventilation and augment the carotid body reactivity to hypoxic stimulus, leading to an exaggerated hyperventilation during hypoxia. These effects had been related to the action of salicylates as uncouplers of oxidative phosphorylation. In the present study, carried out in an in vitro preparation of the rabbit carotid body, we show that acetylsalicylic acid and indomethacin, two anti-inflammatory drugs that are also powerful inhibitors of cyclooxygenase, the prostaglandin-synthetizing enzyme, produce an increase in the [3H]catecholamine release evoked by low oxygen stimulation. The drugs did not affect basal normoxic release, a finding that suggests that at the concentration used these anti-inflammatory agents do not have uncoupling actions, and that their effects on hypoxic-induced release of [3H]catecholamines is mediated by their specific action as cyclooxygenase inhibitors. In agreement with this suggestion we found that prostaglandin E2 completely prevented the effects of both anti-inflammatory agents. In addition, our data indicate that endogenously synthetized prostaglandins are powerful modulators of chemoreceptor cell function. PMID- 1407688 TI - Cocaine-induced disturbances of corticogenesis in the developing murine brain. AB - Exposure of fetuses to cocaine can induce behavioral disturbances and structural modifications of the CNS. Cocaine was injected into pregnant mice from the eighth day of gestation until term and the brains of their offspring were examined at the light and EM levels. Cocaine severely disturbs neocortical architecture, disrupting horizontal and vertical lamination, and inducing abnormal array of the axonal-dendritic bundles. Cocaine also alters several steps of gliogenesis. The severity of the malformations is variable, but evident in all exposed animals. PMID- 1407689 TI - Compartmentalization of NADPH-diaphorase staining in the developing human striatum. AB - Nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) staining of striatal neuropil showed inhomogeneities in human fetal and adult brains. Highly reactive patches were seen during fetal and neonatal period, distributed in a lighter stained background matrix. In adult, zones of low NADPH-d reactivity appeared against darker background staining. NADPH-d reactive patches corresponded to and showed a similar shift in the intensity of staining during development as acetylcholinesterase (AChE) reactive striosomes. PMID- 1407690 TI - Effects of background illuminations on the receptive field size of horizontal cells in the turtle retina are mediated by dopamine. AB - Intracellular recordings from luminosity-type horizontal cells of the turtle retina were used to analyze the effects of steady and flickering background illumination on the size of their receptive fields. Both types of background illumination reduce the size of the receptive field to about the same extent. The reduction seems largely due an increase in the coupling resistance between horizontal cells. The effects of both types of background illumination are sensitive to the dopamine antagonist fluphenazine. This suggests that steady and flickering illuminations stimulate the release of endogenous dopamine. PMID- 1407691 TI - An electrophysiological study of D2 dopaminergic actions in normal human retina: a tool in Parkinson's disease. AB - A peculiar deficit of electrophysiological retinal responses to pattern reversal grating stimuli has been reported in Parkinson's disease (PD) patients. A similar abnormality has been reproduced by means of non-selective dopaminergic antagonists in normal humans. Aim of this study was to verify, by means of a selective D2 antagonist (sulpiride) administered to normal subjects, whether a D2 blockade affects the visual electrophysiological performances with the same trend as observed in PD patients. Patterns electroretinogram (PERG) responses to 1 cycle per degree (c/d) of spatial frequency at 1 (transient) and 7.5 (steady state) Hz of temporal modulation of a square-wave grating pattern reversal have been recorded in 19 healthy volunteers before and after the administration of 100 mg i.m. of sulpiride. The data are consistent for the following conclusion: a selective D2 antagonist reduces steady state and delays transient retinal responses as expected for a PD mimicking agent. PMID- 1407692 TI - Effects of CNS stimulants on the in vivo release of the colocalized transmitters, dopamine and neurotensin, from rat prefrontal cortex. AB - The effect of CNS stimulant drugs on the in vivo release of the colocalized neurotransmitters dopamine and neurotensin in rat prefrontal cortex was studied using microdialysis. Amphetamine, methylphenidate and nomifensine all increased extracellular fluid (ECF) levels of dopamine; however, their effects of neurotensin varied. Amphetamine increased both ECF dopamine (514 +/- 82% of basal) and neurotensin (350 +/- 49% of basal); however, the neurotensin increase lagged behind the increase in dopamine suggesting a possible trans-synaptic effect. Methylphenidate increased both dopamine and neurotensin (226 +/- 26% and 151 +/- 14% of basal respectively) co-synchronously, suggesting exocytosis of vesicles containing both dopamine and neurotensin. The nomifensine-induced increase in dopamine (202 +/- 23% of basal) was similar to that of methylphenidate, whereas the increase in neurotensin was significantly delayed and of lower magnitude (134 +/- 20% of basal). These data suggest that dopamine and neurotensin in part share a common releaseable pool in the prefrontal cortex. Moreover, dopamine may act presynaptically to increase neurotensin release and the different behavioral profiles of these psychostimulants may in part relate to their different effects on neurotensin release. PMID- 1407693 TI - Carnitine palmitoyltransferase activity in the rabbit choroid plexus: its possible function in fatty acid metabolism and transport. AB - The purpose of the present study was to measure the activity of carnitine palmitoyltransferase (CPT) in the lateral and fourth ventricular choroid plexus (LVCP, FVCP) as an example of an enzyme committed to mitochondrial long-chain fatty acid oxidation. The CPT activity measured with both assays determines total CPT activity, that is, the activity of both CPT-A (outer form) and CPT-B (inner form). CPT-assay 1 (forward reaction) activity was 893.3 +/- 44.5 mU/g and 803.3 +/- 71.3 mU/g (mean +/- S.E.M.) in LVCP and FVCP, respectively. CPT-assay 2 (backward reaction) activity was 3673.7 +/- 92.4 and 3417.0 +/- 277.1 mU/g in LVCP and FVCP, respectively. These data demonstrate that CPT activity is present in the rabbit choroid plexus, and that the activity is somewhat higher per gram wet weight of tissue than the activity observed in the skeletal muscle (CPT-assay 1 = 514.4 +/- 159, CPT-assay 2 = 2492 +/- 576 mU/g). CPT activity has been exclusively localized to the mitochondria of the liver, heart, kidney and the skeletal muscles. Our present study further demonstrates that the choroid plexus is another organ in which high activity of CPT exists. PMID- 1407694 TI - Effect of the 5-HT3 receptor antagonist ondansetron on hypothalamic self stimulation in rats and its interaction with the CCK analogue caerulein. AB - It is unclear whether behavioral depression and suppression of food intake by cholecystokinin (CCK) is contributed to by aversive gastrointestinal effects such as nausea. In the present study we examined the effect of a new antiemetic agent, ondansetron, a specific antagonist of 5-HT3 receptors, on suppression of variable interval self-stimulation by the CCK analogue caerulein. Responding by rats for brain-stimulation reward is especially sensitive to CCK, and provides a convenient means of investigating this question. Caerulein (30 micrograms/kg, s.c.), injected alone, was followed by a profound (ca. 80%) reduction in the rate of self-stimulation, lasting about 30 min. Ondansetron (1.0-1000 micrograms/kg, s.c.) injected on its own had no effect on self-stimulation rate, and a 100 micrograms/kg dose did not lessen the depressant action of caerulein. The behavioural depressant effects of CCK are thus unlikely to depend on brain mechanisms for nausea and vomiting involving 5-HT3 receptors. PMID- 1407695 TI - Rhythmic expression of Fos-related proteins within the rat suprachiasmatic nucleus during constant retinal illumination. AB - Within the retinorecipient or ventrolateral subfield of suprachiasmatic nuclei (SCN) in rodents, expression of the protein product of the c-fos proto-oncogene, Fos, is regulated by light. In the present study, the expression of Fos and Fos related proteins within the SCN was examined immunocytochemically for evidence of rhythmic variation in rats sacrificed at different circadian times during exposure to constant retinal illumination (LL). In all animals, nuclear Fos immunoreactivity was mainly confined to an area of the SCN that was coextensive with neuropeptide Y-immunopositive fibers distinguishing the ventrolateral subfield of the nucleus. Moreover, Fos-immunostaining within the ventrolateral SCN of rats exposed to LL fluctuated over the course of the circadian cycle, such that the density of immunopositive cells within this subfield was 2 times greater during the subjective night than during the subjective day. Since Fos expression within the SCN oscillates in the absence of photoperiodic time cues and since the peak of this oscillation coincides with the circadian times when light modulates the periodicity of the SCN pacemaker, these data provide further evidence that expression of the c-fos gene may be a molecular signal in the circadian timekeeping mechanism in the SCN and its regulation by photic stimuli. PMID- 1407696 TI - Seizure related elevations of extracellular amino acids in human focal epilepsy. AB - Intracerebral microdialysis combined with electrocorticographic recordings was used in a patient subjected to epilepsy surgery. The patient developed a series of partial seizures during an 8 min period. Marked elevations of aspartate (79 fold), glycine (21-fold), glutamate (16-fold) and serine (8-fold) dialysate concentrations occurred in association with onset of the period with seizures. Recurrent seizures occurred, in spite of normalizing amino acid levels. Other amino acids analyzed (aspargine, threonine, arginine, alanine, taurine, tyrosine, phenylalanine, isoleucine and leucine) showed less pronounced changes (1-5 times the basal levels). PMID- 1407697 TI - Brainstem influences on biceps reflex activity and muscle tone in the anaesthetized rat. AB - This study analyzes the effect of electrical stimulation of the locus coeruleus (LC) and adjacent brainstem structures on the tonic reflex (TVR), the tonic stretch reflex (TSR) and on muscle tone (MT) in anaesthetized rat. Increases in TVR, TSR and MT of the m. biceps were evoked from regions rostrally and ventrally of LC, the caudal pontine reticular nucleus, the cuneiform nucleus and from the ventral parts of the colliculus inferior. Stimulation of the LC did not influence biceps EMG activity. The results indicate that the observed facilitation of muscle activity is due to stimulation of parts of the mesencephalic locomotor region. It is discussed that the recorded increase in TVR, TSR and MT possibly is due to an excitatory action on alpha motoneurones on one hand and to an enhanced fusimotor drive on the other. PMID- 1407698 TI - Combined histochemical and biochemical demonstration of nigral vulnerability to lipid peroxidation induced by dopa and iron. AB - Using a newly developed lipid peroxidation-inducing system composed of DOPA and iron, we examined the vulnerability of substantia nigra to peroxidation in comparison with that of caudate-putamen obtained from normal or vitamin E deficient animals. Histochemical detection of lipid peroxidation revealed that substantia nigra was far more susceptible than caudate putamen to DOPA and iron treatment, which was biochemically supported by measurements of thiobarbituric acid-reactive substances. Vitamin E deficiency accelerated such susceptibility of substantia nigra but had no influence on the histochemical findings observed in caudate-putamen. PMID- 1407699 TI - Chronic estradiol treatment increases anterior pituitary but not striatal D2 dopamine receptor mRNA levels in rats. AB - The effect of chronic 17 beta-estradiol treatment (10 micrograms, twice each day, for 2 weeks) of ovariectomized rats on D2 dopamine (DA) receptor mRNA levels was investigated in striatum and anterior pituitary gland tissues. We used 32P labeled probes specific for D2 receptor and beta-actin mRNAs in Northern blot analysis. The ratio of D2 DA receptor mRNA/beta-actin mRNA level was significantly increased in the anterior pituitary of estradiol-treated rats compared to vehicle-treated animals. The D2 DA receptor mRNA/beta-actin mRNA ratio in the striatum was not affected by estradiol treatment. However, the medial portion of the striatum showed a significantly lower ratio compared to the lateral portion of the striatum in both vehicle- and estradiol-treated rats. Thus, the estradiol effect on anterior pituitary D2 receptors may implicate transcriptional regulation, whereas our results do not support this hypothesis for the estradiol action on striatal D2 receptors. PMID- 1407700 TI - Vanilloid receptor loss in rat sensory ganglia associated with long term desensitization to resiniferatoxin. AB - A dose-dependent loss of vanilloid receptors (specific [3H]resiniferatoxin binding sites) was found in sensory ganglia of rats 24 h after s.c. administration of resiniferatoxin (RTX), an ultrapotent capsaicin analog. This receptor loss displayed an ED50 of 30 micrograms/kg both in dorsal root and trigeminal ganglia; the ED50 was 6-fold higher than the ED50 for loss of the neurogenic inflammatory response and 30-60-fold higher than the ED50 for desensitization in the standard eye-wiping (chemogenic pain) response. The receptor loss appeared later (24 h) than the loss of the physiological responses (6 h) and showed modest recovery (to 20-30% of control levels) over the following 4 weeks. This vanilloid receptor loss may represent a novel, specific mechanism for vanilloid-induced chronic desensitization. PMID- 1407701 TI - Induction of brain ornithine decarboxylase after systemic or intrastriatal administration of kainic acid. AB - The activity of ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, dramatically increases after different types of brain injuries. The role of this induction is still unclear. We report here data on the temporal pattern of ODC induction caused by the excitotoxin kainic acid. After systemic administration, ODC activity increases severalfold peaking at 8 h in the prefrontal cortex and at 16 h in the olfactory cortex and hippocampus. After intrastriatal injection, the peak of induction is reached at 32 h, while a smaller and more transient increase is also observed in the contralateral, saline injected striatum. We suggest that ODC induction is initially linked to overactivation of neural circuits and, later on, to the development of widespread neural damage. PMID- 1407702 TI - Visually controlled spatial stabilisation of the human head: compensation for the eye's limited ability to roll. AB - During movements of the head in pitch (yes-yes) or in yaw (no-no) the visual scene appears stable whereas rolling the head (ear down to shoulder) induces an apparent swinging of the world in the opposite direction. This visual instability is due to the inadequacy, in the roll plane, of the reflex eye movements which are effective in stabilising the eyes in space during pitch and yaw. We investigated whether head is stabilised in roll to protect against visual instability. Human subjects were fixed in a gimbal with their heads free and were exposed to unpredictable oscillatory movement in pitch and, for comparison roll, about axes aligned with the head. With vision, during roll motion, the head was displaced from upright by approximately half the amplitude of the gimbal motion. In comparison, with eyes closed relying on vestibular and proprioceptive cues and during pitch stimuli with or without vision, the magnitude of head displacement from upright was approximately equal to that to the gimbal. The superior head stability in roll, dependent on a visual frame of reference, compensates for poverty of eye movement in this plane. PMID- 1407703 TI - Microencapsulated nerve growth factor: effects on the forebrain neurons following devascularizing cortical lesions. AB - In this study, we report the effects of nerve growth factor (NGF) delivered into the CNS via a novel delivery system for prolonged, controlled release. The effectiveness of NGF incorporated in the biodegradable microspheres was investigated in the rat model for central cholinergic degeneration. Mature male rats were unilaterally lesioned by disruption of the pia arachnoid vessels and vehicle (alginate microspheres without NGF) and microencapsulated NGF was placed at the site of the lesion. Choline acetyltransferase (ChAT) activity was measured in the nucleus basalis magnocellularis (NBM) and cortex in the (a) non-lesioned control animals; (b) lesioned animals treated with 'empty' microspheres and (c) lesioned animals treated with microspheres containing NGF, 30 days following surgery. Similarly lesioned animals received NGF via permanently installed cannulae in order to compare the novel route of administration with the more conventional one. Immunocytochemical results showed an absence of the cholinergic cell body shrinkage in the NBM otherwise observed in lesioned animals. Furthermore, an increase in intensity of ChAT immunostaining in NGF-treated, lesioned animals was evident. The present results stress the experimental therapeutic possibilities of novel delivery systems for administration of trophic factors in the CNS. PMID- 1407704 TI - Leukemia inhibitory factor (LIF) mediated increase of choline acetyltransferase activity in mouse spinal cord neurons in culture. AB - The effects of leukemia inhibitory factor (LIF) on choline acetyltransferase (ChAT) enzyme activity in cultured mouse spinal cord neurons were examined. The administration of LIF to cultures at concentrations of 10 U/ml and higher enhanced ChAT activity approximately 3- to 4-fold in cultured spinal cord neurons. Among neurotrophic factors tested, basic fibroblast growth factor (bFGF) and insulin-like growth factor I (IGF-I) stimulated the development of ChAT activity but to a smaller extent than LIF, while interleukin 3 (IL-3), interleukin 6 (IL-6) and nerve growth factor (NGF) showed no apparent effect on ChAT development. Our results indicate that LIF, which has not been known to have any trophic effect on mammalian central nervous system neurons to date, acts as a potent differentiation factor for ChAT in cholinergic neurons of mouse spinal cord in culture. PMID- 1407705 TI - Involvement of a receptor for neurite outgrowth factor (NOFR) in cerebellar neurogenesis. AB - A receptor for neurite outgrowth factor (82 kDa membrane protein, NOFR) was detected in the developing chick cerebellum by immuno- and ligand blots. In immunohistochemical study, NOFR was maximally expressed in the external granular layer of cerebellum at embryonic day 10-12 and gradually decreased until embryonic day 18. Neurite outgrowth and cell migration induced by NOF from cerebellar explants were completely suppressed by the addition of anti-NOFR IgG. These results suggest that NOFR plays an important role in the cerebellar neurogenesis. PMID- 1407706 TI - Mesolimbic dopamine release elicited by activation of the accessory olfactory system: a high speed chronoamperometric study. AB - Male rats were anesthetized with chloral hydrate, and extracellular dopamine concentrations in the nucleus accumbens were measured using high speed chronoamperometry. Recordings were obtained during application of air passed through bedding obtained from cages that housed estrus female rats and application of depolarizing concentrations of potassium (K+) to the accessory olfactory system. Application of bedding-impregnated air increased the electrochemical signal obtained from within the nucleus accumbens, and this response was enhanced by treatment with the DA re-uptake blocker, GBR-12909. Application of K+ to the vomeronasal nerve layer of the accessory olfactory bulb and to the accessory olfactory bulb, itself, also elicited increases in the electrochemical signal recorded from the nucleus accumbens. These results indicate that the accessory olfactory system is able to activate the mesolimbic DA system. PMID- 1407707 TI - Accumulation of alpha B-crystallin in brains of patients with Alexander's disease is not due to an abnormality of the 5'-flanking and coding sequence of the genomic DNA. AB - alpha B-Crystallin is a major protein component of Rosenthal fibers, which massively accumulate in the brains of patients suffering from Alexander's disease. To examine whether or not accumulation of alpha B-crystallin is due to any abnormality of the gene structures, we determined the sequence of the alpha B crystallin gene in two cases of pathologically confirmed Alexander's disease. Direct sequencing of the promoter and coding regions of the alpha B-crystallin gene in patients revealed them to have a normal sequence. Northern blotting showed a single alpha B-crystallin mRNA species expressed in the Alexander's disease brain. PMID- 1407708 TI - Neuromuscular compartments in the human biceps brachii muscle. AB - Electrophysiological evidence suggests that the human biceps brachii muscle is organized into functional neuromuscular compartments. The purpose of this study was to determine whether there was an anatomical basis for these compartments. Dissection of the biceps revealed both architectural and nerve branching pattern compartmentalization within the muscle. Although the biceps brachii is grossly subdivided into long and short heads, these heads are further subdivided into roughly parallel architectural compartments. Moreover, these architectural compartments usually receive a private nerve branch, thus supporting the notion that the human biceps brachii has neuromuscular compartments. PMID- 1407709 TI - Responses of rat substantia nigra pars reticulata units to cortical stimulation. AB - In order to study the function of multiple pathways between the sensorimotor cortex (Cx) and the substantia nigra pars reticulata (SNr), responses of SNr units to stimulation of the Cx were studied in anesthetized rats. Most of the units (229 of 236) exhibited repetitive firing with fairly short, regular intervals. The other 7 units displayed long duration spikes, irregular firing intervals and slow spontaneous firing. Stimulation of the Cx usually resulted in a short latency excitation and occasionally a long latency inhibition in both types of units. When strong stimulation was applied, multiple excitatory and inhibitory responses alternating each other with about a 25 ms interval were observed. SNr units responded with different patterns and latencies to stimulation of different sites of the sensorimotor Cx. The results indicate that signals derived from the sensorimotor Cx reach the SNr via multiple pathways and converge on many SNr neurons. PMID- 1407710 TI - Periaqueductal gray matter stimulation-produced analgesia in diabetic rats. AB - The effect of diabetes on periaqueductal gray matter (PAG) stimulation-produced analgesia (SPA) was examined in rats. PAG SPA was assessed using the tail-pinch test. PAG stimulation produced marked analgesia in both naive and diabetic rats. Furthermore, the degree of PAG SPA did not differ between naive and diabetic rats. PAG SPA was significantly attenuated by a low dose (0.5 mg/kg, s.c.) of naloxone in naive rats, but not in diabetic rats. However, a high dose (5 mg/kg, s.c.) of naloxone significantly and equally attenuated PAG SPA in both naive and diabetic rats. On the other hand, the analgesic potency of morphine (3 mg/kg, s.c.) was significantly reduced in diabetic rats as compared with naive rats. These results suggest that PAG SPA in diabetic rats may be mediated by different opioid receptor interactions as compared with naive rats. PMID- 1407711 TI - Structural maturation of synapses in the rat superior cervical ganglion continues beyond four weeks of age. AB - We have examined the morphology of preganglionic synapses in the rat superior cervical ganglion (SCG) at 10 days, 4 weeks and 1 year. Between 10 days and 4 weeks the mean thickness of the postsynaptic density (PSD) increased from 45.9 +/ 0.1 nm to 52.1 +/- 1.7 nm (P = 0.017), the mean length of the PSD (0.41 +/- 0.02 microns) did not change, and the distribution of synapses on the neuronal surface changed with a decrease in the proportion of somatic and an increase in the proportion of dendritic spine synapses. Since both synapse elimination and synapse formation are occurring during this period several mechanisms may contribute to these changes. However, between 4 weeks and 1 year, when there is no net change in the number of synapses, the mean length of the PSD increased to 0.53 +/- 0.02 microns (P = 0.001), there was no change in either the mean thickness of the PSD or the distribution of the synapses but the proportion of concave ('smile') synapses increased. A comparison with previous developmental studies of synapses in cerebral cortex of rat and chicken indicate that both the nature and the rate of synapse maturation can vary between different populations of synapses. PMID- 1407712 TI - Age-dependent effects of deafferentation of the rat superior cervical ganglion on expression of P65 (synaptotagmin) during postnatal development. AB - Previous studies have shown that deafferentation of the rat superior cervical ganglion (SCG) alters the levels of p65 (synaptotagmin), a synaptic vesicle integral membrane protein, within the ganglion. Neonatal deafferentation blocks normal postnatal increases in p65, while deafferentation in adult animals produces a transient increase in p65 expression. The present study examines the time course of the shift from the neonatal to adult pattern of response to deafferentation. Neonatal and 7 day old rats showed the neonatal response to deafferentation. Ganglia from rats aged 14 days or older at deafferentation exhibited the transient increase in p65 at 7 days after surgery. The shift from the neonatal to adult response occurs during the second postnatal week. The change in response to deafferentation may be associated with refinement of synaptic function in a manner yet to be determined. PMID- 1407713 TI - N-methyl-D-aspartate responses in rat cerebellar granule cells are modified by chronic depolarisation in culture. AB - Following culture in high (25 mM) K+ conditions cerebellar granule cells only respond with a rise in cytosolic free calcium concentration ([Ca2+]i after removal of external Mg2+. When granule cells are grown in low (5 mM) K+ N-methyl D-aspartate (NMDA) exerts a neurotrophic effect. We show that at the critical time for this effect NMDA will elicit a rise in [Ca2+]i in 5 mM K+ cultures even in the presence of Mg2+ and that growth in 25 mM K+ induces the rapid appearance of a Mg2+ block of NMDA receptors in granule cells. This suggests firstly, that a rise in [Ca2+]i could be involved in the neurotrophic effect of NMDA and secondly, that the characteristics of the NMDA responses in granule cells are modified as a result of growth under depolarising conditions. PMID- 1407714 TI - The new growth factor pleiotrophin (HB-GAM) mRNA is selectively present in the meningothelial cells of human meningiomas. AB - The distribution of the messenger RNA coding for the recently cloned growth factor pleiotrophin (HB-GAM) was studied in human benign meningiomas using in situ hybridization histochemistry and oligonucleotide probes. Pleiotrophin mRNA was selectively found in the meningothelial cells whilst not detected in the fibroblastic cells, blood vessels and collagen bundles of the meningiomas. PMID- 1407715 TI - Push-pull modulation of ganglion cell responses of carp retina by amacrine cells. AB - The responses of a ganglion and an amacrine cell were recorded simultaneously in the carp retina. Sinusoidal current injected into amacrine cells modulated ganglion cell discharges either in phase (excitation) or in opposite phase (inhibition). ON-center ganglion cells received excitatory inputs and OFF-center ganglion cells received inhibitory inputs from ON-center amacrine cells. They received inputs of opposite polarity from OFF-center amacrine cells. Namely, inputs from ON-center and OFF-center amacrine cells augment the responses of ON center and OFF-center ganglion cells in a push-pull manner. PMID- 1407716 TI - Possible involvement of interleukin-1 in ischemic brain edema formation. AB - To determine the contribution of interleukin 1 (IL-1) on ischemic brain edema formation, the effect of recombinant human interleukin 1 beta (rhIL-1 beta), or zinc protoporphyrin (ZnPP) as an IL-1 blocker, on brain edema was studied in rats. The animals were subjected to 60 min of ischemia in a middle cerebral artery occlusion model. Immediately after reperfusion, rhIL-1 beta at a dose of 10 ng/2 microliters, or ZnPP at doses of 1 and 10 micrograms/2 microliters were topically applied into lateral cerebroventricle. In rhIL-1 beta-treated rats, ischemic brain edema formation was significantly increased in the dorsal and ventral areas of the caudate putamen 24 h after reperfusion, compared to that of vehicle-treated control rats. Furthermore, in ZnPP-treated rats, brain edema was decreased in both caudate-putamen areas. This suggests that IL-1 plays an important role in pathogenesis for post-ischemic brain edema. PMID- 1407717 TI - Mapping of the cochlear nucleus subregions in the rat with neuronal Fos protein induced by acoustic stimulation with low tones. AB - To explore the mode of appearance of Fos, a gene product of proto-oncogene c-fos, in the cochlear nucleus, a pure tone was given to rats and Fos was detected by immunohistochemistry. Following low-tone stimuli applied with moderate ranges of sound intensity, neurons with Fos-label occurred band-like in the ventral subregions of the dorsal cochlear nucleus. Organization of low-to-high tones in the ventral-to-dorsal orientation became visible at the caudal level. Several other subnuclei consistently exhibited Fos with no topographic pattern. Neurons interspersed in the adjoining vestibulocochlear nerve were also found to elicit Fos. Low-tone stimuli with very high sound intensity led to a rather widespread distribution of Fos, making the tone-specific distribution less visible. PMID- 1407718 TI - Regional effects of MK-801 on dopamine and its metabolites studied by in vivo microdialysis. AB - The non-competitive N-methyl-D-aspartate receptor antagonist MK-801 was observed to have regionally specific effects on the extracellular concentration of dopamine and its metabolites. In rat anterior striatum, MK-801 transiently decreased extracellular dopamine, in spite of inducing intense circling behaviour which is generally associated with an increase in this neurotransmitter. In contrast, hippocampal extracellular dopamine was increased in a dose-related manner by MK-801. The possible significance of these data is discussed in relation to some of the known behavioural actions of MK-801. PMID- 1407719 TI - The transcription factor CREB, but not immediate-early gene encoded proteins, is expressed in activated microglia of lumbar spinal cord following sciatic nerve transection in the rat. AB - Expression of CREB, JUN, FOS and KROX-24 proteins was investigated in glial cells of the lumbar spinal cord. In untreated rats, CREB, c-JUN and JUN D were present in glial cells of the ventral and dorsal horn. Following sciatic nerve transection, the number of CREB immunoreactive glial cells increased in both the ipsilateral ventral and dorsal horns between 24 h and 48 h, reached a maximum after 5 days and returned to control levels after 20 days. Counterstaining with Cresyl violet, a general stain of cells, revealed that the increase of CREB positive glial cells was congruent with the increase of the number of glial cells. Staining with GFAP, a marker for astrocytes, showed an increase in intensity of labelling but no change in number of GFAP labelled cells. This indicates a constitutive expression of CREB in activated microglia. The number of glial cells labelled by c-JUN and JUN D did not change, and glial cells were not labelled by FOS and KROX-24 proteins following sciatic nerve transection. These findings demonstrate that proliferation and differentiation of glial cells in vivo can occur in absence of JUN, FOS and KROX proteins. PMID- 1407720 TI - Oral naloxone reduces constipation but not antinociception from oral morphine in the rat. AB - Oral administration of naloxone (10 mg/kg) antagonized the slowing of the intestinal transit caused by oral morphine (1, 2.5 and 5 mg/kg) in rats. Oral administration of naloxone (10 mg/kg) did not prevent the antinociceptive effect of orally administered morphine (2.5 mg/kg) in the tail-flick test carried out on rats. It is concluded that oral naloxone locally blocks the constipating effect of morphine, while it fails to reduce the central action of morphine due to extensive metabolization after oral administration. PMID- 1407721 TI - Selective blockade by yohimbine of descending spinal inhibition from lateral reticular nucleus but not from locus coeruleus in rats. AB - The present study was undertaken to compare the effects of the alpha 2 adrenoceptor antagonist yohimbine on inhibition of C-fiber-evoked responses of dorsal horn neurons produced by electrical stimulation of the lateral reticular nucleus (LRN) and the Locus coeruleus (LC) in the rat. In the majority of neurons, C-fiber-evoked responses were significantly inhibited by 53.84 +/- 5.02% and 57.63 +/- 5.79% of control by LRN and LC stimulation, respectively, whereas in less than half of the neurons, A-fiber-evoked responses were reduced by 20.99 +/- 6.06% and 21.78 +/- 4.48% of control, respectively. After systemic or spinal administration of yohimbine, LC-induced inhibition of C-fiber-evoked responses was not affected. In contrast, LRN-induced inhibition was markedly attenuated by yohimbine. The results suggest that alpha 2-adrenoceptors may be involved in mediation of inhibition of spinal nociception induced by stimulation of LRN but not by LC. PMID- 1407722 TI - Vasopressin administration via microdialysis into the septum interferes with the acquisition of spatial memory in rats. AB - The role of vasopressin (AVP) in the septohippocampal system in spatial memory was studied in 27 male hooded rats of the Long-Evans strain. The rats were implanted with a septal microdialysis probe and assigned to 3 groups. Two days later, they were trained on 3 consecutive days (12 daily trials) to locate the hidden underwater platform in the Morris water maze (MWM) while the probes were perfused with either artificial cerebrospinal fluid (aCSF) or aCSF containing vasopressin or the V1 antagonist d(CH2)5Tyr(Me)AVP (AAVP). Another group of rats (n = 8) remained untreated. Groups receiving microdialysis of aCSF or AAVP acquired the MWM task at the same rate as untreated animals. On the other hand, place navigation learning was significantly impaired by microdialysis of AVP during all sessions. The results indicate that endogenous AVP (at least that affecting the V1 receptor subtype) is not indispensable for the acquisition of spatial memories in the MWM, whereas excessive presence of synthetic AVP interferes with spatial learning. PMID- 1407723 TI - Localisation of striatal muscarinic receptors involved in dopamine receptor mediated behavioural responses. AB - Stereotyped sniffing responses to the direct dopamine agonist, apomorphine, were assessed following intrastriatal injection of the alkylating derivative of oxotremorine, BR 401. Subsequently, the localisation and extent of muscarinic receptor alkylation after injection into various striatal sites were assessed by quantitative autoradiography. The results of these experiments provide evidence that a regional subset of striatal muscarinic receptors is involved in apomorphine-induced stereotyped sniffing. In addition, these receptors are localised in a similar area to that previously shown to contain the dopamine D2 receptors responsible for mediating apomorphine-induced sniffing. Thus, striatal muscarinic receptors involved in dopamine-agonist induced behaviours share a close anatomical association with the dopamine receptors at which the agonist acts. PMID- 1407724 TI - Azimuthal processing in the posterior auditory thalamus of cats. AB - The responses to free-field acoustic stimuli of 157 units in the auditory thalamus of anesthetized cats were studied in relation to the localization of pure tone stimuli in the azimuthal plane. Units were classified as 'directional' if their firing rates at sound levels in excess of 20 dB above threshold varied by more than 50% as a function of azimuth. Sixty-five % of the units in the nucleus of the brachium of the inferior colliculus and 30% in the ventral division of the medial geniculate body were found to be directional, suggesting different processing channels for sound localization between colliculus and cortex. PMID- 1407725 TI - Interaction of long chain n-alkyl diamines with the NMDA receptor complex. AB - Long chain 1, omega-diamines with 8, 10, 12, 14 and 16 carbon atoms reduced the binding of [3H]MK 801 to rat hippocampal membranes with IC50 values of 333, 72, 16.5, 4.7 and 4.3 microM, respectively. In the presence of medium-effective concentrations of the diamines, the concentration response curve of the stimulation by the polyamine spermine was shifted to higher spermine concentrations, reaching similar maximal stimulation as in the absence of the diamines. In the case of 1,12-diaminododecane (N-12-N) and 1,14 diaminotetradecane (N-14-N), the extent of this shift was compatible with competitive antagonism of spermine. Inhibition of [3H]MK 801 binding by long chain diamines was sensitive to spermine, inhibition by N-12-N and N-14-N exhibited the highest sensitivities. Of all diamines tested, N-12-N and N-14-N seem to be the most likely candidates for inverse polyamine agonists. PMID- 1407726 TI - The cone electrode: ultrastructural studies following long-term recording in rat and monkey cortex. AB - The achievement of long-term recording of neural signals from the central nervous system has potential clinical and investigative application. To facilitate long term recording, a novel cone electrode composed of an insulated gold wire within a hollow glass cone had been developed. Cone electrodes containing sciatic nerve or neurotrophic medium were implanted into cerebral cortex in rats and monkeys. Electrophysiologic recordings had been previously obtained from cone tissue for as long as 15 months following implantation and this tissue contained silver positive processes. We now extend these observations to characterize the fine structural features of the tissue within these long-term implants. Electron microscopy revealed central myelinated axons, dendrites, synaptic profiles, blood vessels, and glia; peripheral nerve was not found in the cones in which sciatic nerve had been placed. These observations further suggest ingrowth of cortical neurites and elements into the hollow glass tip of the cone and support the feasibility of long-term recording using this electrode. PMID- 1407727 TI - Quantification of beta A4 protein deposition in the medial temporal lobe: a comparison of Alzheimer's disease and senile dementia of the Lewy body type. AB - The distribution of beta-amyloid protein (beta A4) was examined in the medial temporal lobes from cases of Alzheimer's disease (AD) (n = 13), senile dementia of Lewy body type (SDLT) (n = 12) and age matched controls (n = 9). Using a previously described image analysis technique the extent of beta A4 pathology was determined in ten distinct anatomical sites within the medial temporal lobe. AD and SDLT cases contained very similar amounts of beta A4 in the areas sampled and both contained significantly more beta A4 than the age matched controls, particularly in the dentate and parahippocampal gyri. The similarity of the beta A4 load in the two conditions is in contrast to reported differences in the number of neurofibrillary tangles which can be observed. It is suggested that AD and SDLT represent a spectrum of pathology which centres around the aberrant processing of the beta A4 precursor protein. PMID- 1407729 TI - An interdisciplinary approach to teaching specimen collection. PMID- 1407728 TI - Student awareness of research findings. AB - One problem faced by all faculty who teach research to undergraduate students is how to make the topic of utilization of research both interesting and practical. The author describes an approach that elicited students' active participation in replicating an earlier study by indicating their awareness of research-validated practices. Involvement of the students in an actual study seems a positive way to introduce the topic of utilization and has been used with success in one program over the past 4 years. PMID- 1407730 TI - A model for peak performance. AB - This study identified major factors that contributed to peak performance among eight nursing educators. The peak performers were interviewed 3 times over 8 years. Intense commitment to a mission, continual performance assessment, concentration on satisfaction and rewards, and the ability to set priorities and seek social support were delineated as factors in peak performance. Commitment to a personal mission that aligns with the demands of the university was a peak performer's ultimate personal investment and service to students and the university. PMID- 1407731 TI - Classroom shared governance. AB - As shared governance increases in organizations that employ nurses, it becomes an essential element of professional socialization and preservice education. Framing a course in concepts of shared governance offers students experiential learning in uses of power, accountability, organizational decision making, and peer negotiation. The authors present concepts and examples of classroom shared governance from student and teacher perspectives. PMID- 1407732 TI - Cooperative learning and the nursing process. PMID- 1407733 TI - Nursing education and HIV disease: a call for action. AB - The continued increase in reported cases of HIV disease has created a compelling need for nursing educators to provide students with comprehensive information on HIV-related issues. The authors discuss the need for students to care for HIV positive individuals under faculty supervision to overcome fear and anxiety. Faculty education is proposed as a first step to develop a comprehensive approach to HIV education. A guide for integrating HIV content into the curriculum is provided. PMID- 1407734 TI - Making a challenge out of an NLN visit: any more questions? AB - Any educator, regardless of experience, feels apprehension as the final preparations are made for a National League for Nursing (NLN) review. Recognizing that 70% of our faculty had never experienced the review process, school administrators decided to take a novel approach to prepare faculty for the NLN visit. The authors discuss program development for a faculty workshop that modeled a popular television game show. PMID- 1407735 TI - An opportunity to create healthcare policy: nonprofit board membership. PMID- 1407736 TI - A rural nursing practicum: making it work. AB - Inciting the interest of baccalaureate students in the practice of nursing in a rural setting has been an ongoing challenge for many educators. The authors identify difficulties they encountered when attempting to involve students in a rural nursing practicum and delineate several strategies used to overcome these difficulties. PMID- 1407737 TI - Positive reinforcement in clinical teaching. AB - Contrary to the idea that nursing students are intrinsically motivated, findings in research studies show that students repeatedly report the significance of positive feedback to them. Delivery of positive reinforcement by clinical instructors can be developed so that the reinforcement is more meaningful to students and more effective in promoting or maintaining desired student behaviors. PMID- 1407738 TI - SN to GN to RN: facilitating the transition. PMID- 1407739 TI - Using cooperative learning strategies. AB - Nurse educators are challenged to develop innovative teaching strategies that help students think critically and interact skillfully with others. The authors present the merits of cooperative learning and describe ways that nurse educators can teach essential content using this educational strategy. PMID- 1407740 TI - Integration of cultural content into a psychiatric nursing course to change students' attitudes and decrease anxiety. PMID- 1407741 TI - Curriculum planning for the part-time student. PMID- 1407742 TI - Empowerment for teachers and students. PMID- 1407743 TI - Computerized cost analysis for the nursing skills laboratory. AB - Cost control and accountability are requirements in the academic world of the 1990s. The author describes a computerized cost analysis system in the nursing skills laboratory that enables administrators to determine the cost of teaching skills, increases efficiency level of teaching by the faculty, and provides data for budgeting and ordering expendable medical supplies. PMID- 1407744 TI - Exercise and lean weight: the influence of body weight. AB - Exercise can produce a modest gain of lean body mass (LBM) and loss of fat in weight-stable individuals, but it is important to realize that if much weight is lost during exercise there is a risk of some erosion of the LBM. Data from both human and animal experiments show that exercise cannot conserve lean weight in the face of significant energy deficit, although moderate obesity affords a modicum of protection in this respect. PMID- 1407745 TI - Should enteral nutrition be considered as primary therapy in acute Crohn's disease? AB - Clinical trials indicate that elemental enteral diets are equally as effective as corticosteroid treatment for acute Crohn's disease; however, a clear efficacy of polymeric formulas has yet to be demonstrated. Moreover, the mechanism of action of enteral nutrition remains uncertain, and further study is needed to define the precise role of specialized enteral formulas in the long-term management of this disease. PMID- 1407746 TI - Low-calcium diets enhance phytate-phosphorus availability. AB - This study showed that, in chickens, the negative effects of phytate-phosphorus in a low inorganic phosphorus diet could be completely reversed through the additive effects of reduced dietary calcium and increased cholecalciferol. In the future, perhaps greater reliance on more readily available plant phosphorus sources may be instituted in developing countries, where cheap sources of inorganic phosphorus are difficult to obtain. PMID- 1407747 TI - Use of gene therapy to correct elevated LDL levels in LDL-receptor deficient rabbits. AB - Recent studies using gene therapy to correct low-density lipoprotein (LDL) receptor deficiency in rabbits suggest that practical applications of such techniques may be forthcoming. While complete correction of elevated serum cholesterol levels resulting from LDL-receptor deficiency is not yet possible, significant reductions were possible following gene therapy. PMID- 1407748 TI - Fish oil consumption influences mortality rates of mice challenged with Salmonella typhimurium. AB - A recent report has shown that dietary fish oil consumption increases mortality in mice challenged with Salmonella typhimurium. The mechanism of this effect is uncertain, however. PMID- 1407749 TI - Regular or decaf? Coffee consumption and serum lipoproteins. AB - Epidemiologic studies indicate that the relationship between coffee consumption and cardiovascular disease is inconsistent. The potential impact of caffeinated vs. decaffeinated coffee on serum lipids has been investigated with similar inconclusive findings. Understanding the effects that various types of coffee beverages may have on serum lipids could be enhanced by identifying and characterizing the putative lipid-altering factor in coffee. PMID- 1407750 TI - The changing face of European nutrition. PMID- 1407752 TI - Trace element-gene interactions. AB - For many of the genes encoding proteins involved in the transport, storage, and function of the trace elements, expression is regulated by the availability of the elements concerned. This control is exercised through a variety of mechanisms, including metal-activated transcription factors, modified usage of stop codons, and use of secondary structure within mRNA to regulate its translation and stability. Two widely represented groups of transcription factors, often classed as zinc-finger proteins, depend on constituent zinc ions for their activity. In addition, the sensitivity of growth and fetal development to the lack of zinc is hypothesized to relate to a requirement for the element during certain critical alterations in gene expression. The evidence for this and possible underlying mechanisms is examined. PMID- 1407753 TI - Nutrition and aging: potentials and problems for research in developing countries. AB - The demographic explosion of persons over 60 years of age is a reality in developed and developing countries alike. There is evidence that research on aging and nutrition in Third World countries is growing and developing. Specific research programs, and the linking of these programs in timely multicenter efforts, promise both valuable descriptive research for the benefit of national populations and comparative insights that will help us to learn more, collectively, about the intrinsic nature of the aging process itself. PMID- 1407751 TI - Antioxidants and HIV infection. PMID- 1407754 TI - Cysteine-rich intestinal protein (CRIP): a new intestinal zinc transport protein. AB - Cysteine-rich intestinal protein (CRIP) is a newly identified peptide that occurs primarily in the intestine and binds zinc in the mucosa during absorption. High dietary zinc does not affect CRIP concentration, but it greatly increases metallothionein, which may compete with CRIP to decrease zinc absorption. PMID- 1407755 TI - Women on the short end of the loaf: intrahousehold food allocation among members of poor Nepalese families. AB - Intensive and structure intrahousehold observations of the pattern of food allocation in poor rural Nepalese households indicate no difference in the distribution of nutrients between male and female children. In contrast, preferential food distribution patterns among adults show that women are less likely to achieve recommended levels of some nutrients than are men of the same age. PMID- 1407756 TI - Iron overload in sub-Saharan Africa involves a genetic component. AB - A new study suggests that the iron overload observed in sub-Saharan Africans may be due to more than elevated iron intake. Genetic analysis indicates that a heritable, but unidentified, trait may account for a substantial portion of the variability in transferrin saturation seen in persons with iron overload. This defect may occur in over 30% of the population and appears to be distinct from the genetic factor controlling hemochromatosis in Caucasian populations. PMID- 1407757 TI - The Medford Declaration to end hunger in the United States. PMID- 1407758 TI - Hunger in the United States: policy implications. PMID- 1407759 TI - Yale article on advanced practice nursing is of overwhelming importance to NPs. PMID- 1407760 TI - Allergen avoidance in the treatment of dust-mite allergy and asthma. AB - House-dust-mite allergen is one of the primary causes of asthma. In many instances, asthma is an immunoglobulin gamma E mediated atopy (i.e., allergen specific hypersensitivity) that leads to non-specific bronchial hyper-reactivity and subsequent symptom manifestations. These symptoms may range from an annoying cough to full-blown respiratory failure. Allergen-avoidance measures should be a primary mode of treatment for atopic asthmatics. This article focuses on the dust mite allergen and its relationship to asthma. It details specific avoidance measures that should be implemented by the majority of asthmatics. Studies are cited that support the aggressive use of these measures to decrease allergen exposure, and to subsequently prevent or significantly reduce asthma symptoms. When health care providers have a better understanding of avoidance measures and the rationale underlying their use, these measures are more likely to be valued and given greater emphasis in education and treatment plans. Renewed emphasis on an immunomodulatory approach to asthma treatment may help to reverse the rise in asthma morbidity and mortality rates. PMID- 1407761 TI - New studies, new treatments, new organization discussed at national NP symposium. PMID- 1407762 TI - Advanced practice nursing article provides compelling reasons for legislative reform. PMID- 1407763 TI - Council's pursuit of national standardization for advanced practice nursing meets with resistance. PMID- 1407764 TI - Reader identifies yogurt containing culture effective in relieving candidal vaginitis. PMID- 1407766 TI - NPs play major role in promoting sexuality among institutionalized elderly. PMID- 1407765 TI - Reader offers strategies for identification and treatment of dilutional hyponatremia. PMID- 1407767 TI - NP's contributions are honored by a colleague. PMID- 1407768 TI - American Cancer Society offers specific guidelines for detecting and managing breast abnormalities. PMID- 1407769 TI - Assessing school readiness through the school-entry screening exam. AB - Although there exists no perfect screening tool that is predictive of a child's success in school, an office visit prior to school enrollment can detect potential problems. This visit should include a history and physical, and developmental assessment. The developmental assessment involves a sampling of a child's abilities in the areas of language, reasoning, gross and fine motor skills, and personal-social development. Providers must be alert to signs and symptoms indicating impediments to learning. Clinicians who are knowledgeable about trends in education regarding readiness testing, birth-date cutoffs and retention can serve as a valuable resource to parents. The clinician can also be a major contributor to the achievement of national education goals set forth by the Bush administration. Ten tools for assessing children are compared, and their appropriate use is discussed. PMID- 1407770 TI - Frontier areas: opportunities for NPs' primary care services. AB - Demographers have recently designated frontier areas as distinct from other rural areas. Frontier counties are defined as those with less than six persons per square mile; as such, they constitute 45 percent of the U.S. land mass and include 2.2 million people. The health status among frontier residents is estimated to be lower than that of other rural or urban populations, and frontier health services, particularly primary care services, are scant. In this article, opportunities for nurse practitioners in frontier practice are explored, including specific suggestions for the development of new frontier NP practices. PMID- 1407771 TI - The legal danger of written protocols and standards of practice. AB - Nurse practitioners have historically developed protocols and standards of practice to guide and improve the quality of their patient care. Written protocols and standards of practice can, however, create a potential malpractice problem. Lawyers who bring malpractice cases on behalf of patients will use the protocols and standards to measure the practitioner's care. The practice standards are often too high to be reasonably met by practitioners at all times and in all settings. As a result, the practitioner's care may breach those standards. Nurse practitioners should develop protocols that are based on a minimum safe level and not the maximum level aimed at ideal care. Standards and protocols should be updated and realistic. Once developed, protocols and standards must be followed precisely to limit potential liability. PMID- 1407772 TI - An update on cephalosporins. PMID- 1407773 TI - NONPE offers thoughts on licensure. PMID- 1407774 TI - How to apply an ice bag, ice collar, or ice glove. PMID- 1407775 TI - Evaluating sodium levels. PMID- 1407776 TI - Myths & facts ... about septic shock. PMID- 1407777 TI - Responding to an air embolism. PMID- 1407778 TI - The shattering consequences of C.P.R. PMID- 1407779 TI - Using peak flow meters. PMID- 1407780 TI - A voice from the past. PMID- 1407781 TI - When a spouse dies. PMID- 1407782 TI - How to stabilize a percutaneous tube. PMID- 1407783 TI - Determining discharge priorities. PMID- 1407784 TI - Treating pressure ulcers with a myocutaneous flap. PMID- 1407785 TI - Vaccine series for hepatitis B. PMID- 1407786 TI - Frankie was never satisfied ... until she made a new connection with life. PMID- 1407787 TI - To find a soul. PMID- 1407788 TI - Assessing wound drainage. PMID- 1407790 TI - Making time work for you. PMID- 1407789 TI - Mary's last wish. PMID- 1407791 TI - Fitting in on the unit. Work culture is the key. PMID- 1407792 TI - Diamond in the rough. PMID- 1407793 TI - Even night drug cabinet can cause problems. PMID- 1407794 TI - The physician and the courts. PMID- 1407795 TI - Television physicians. PMID- 1407796 TI - Cardiovascular risk factors in Native American children. AB - Information concerning cardiovascular disease risk factors in Native American children is limited. In adult Native American populations, cardiovascular disease risk factors of non-insulin dependent diabetes mellitus, obesity, and cigarette smoking are prevalent, and recent reports indicate mortality caused by cardiovascular disease has dramatically increased. In a screening program at the Onondaga Nation School, six cardiovascular disease risk factors were evaluated. Of 95 school children, 55 representing 39 interrelated families, participated. Family histories were positive for diabetes mellitus in 72%, for cardiovascular disease in 54%, and for passive smoking in 90% of families. Physical examinations of the children revealed obesity (weight/height greater than 90th percentile) in 42% and hypertension (systolic or diastolic blood pressure/height greater than 95th percentile) in 22%. Fingerstick cholesterol levels (Reflotron system) were greater than 170 mg/dL in 25%. Overall, 85% of participants had three or more risk factors for cardiovascular disease. The study results indicate that Onondaga Native American children are at significant risk for cardiovascular disease; programs for identification and modification of cardiovascular disease risk factors are urgently needed. PMID- 1407797 TI - The persistent vegetative state: an analysis of clinical correlates and costs. AB - A review was compiled of 23 patients in the persistent vegetative state; a condition that developed while the patients were in an acute care hospital. Before the onset of the persistent vegetative state, eight patients had had dementia, 11 were functionally dependent, and seven had neurologic disorders that gradually led to the persistent vegetative state. For patients in the persistent vegetative state, three types of mechanical support--respirators, nasogastric or gastrotomy tubes, and intravenous lines--were utilized. All three were necessary in 43% of patients, two types in 52%, and one type in 4%. All patients in the persistent vegetative state required at least one type of mechanical assistance. Their course was complicated in all cases by incontinence, and in the majority, by decubiti, pneumonia, and urinary tract infection. Only one patient improved enough to be able to say a few words. These patients required active medical care and invasive procedures that were costly but futile. The hospital bills obtained for 13 patients averaged $170,000, and the length of stay for all patients averaged 197 days, the equivalent to a total number of bed-days of 12.5 bed years. The poor outcomes, requirements for mechanical support, and frequency of complications--especially when neurologic impairments were present before the onset of the persistent vegetative state--should be considered when evaluating the cost in hospital bills and bed occupancy. PMID- 1407798 TI - Catfight in the labs. PMID- 1407799 TI - Not a valentine. PMID- 1407800 TI - Physician-assisted suicide. PMID- 1407801 TI - History--the great reminder. The relationship between the Long Island College Hospital and the State University of New York Health Science Center at Brooklyn. PMID- 1407802 TI - Health care for seamen in the Port of New York. Part II: The rise of the Seaman's Retreat. PMID- 1407803 TI - Do tricyclic antidepressants have a protective effect in post-traumatic stress disorder? PMID- 1407804 TI - Progressive pulmonary thromboembolism in association with HIV disease. PMID- 1407805 TI - Unexpected reversal of an idiopathic dilated cardiomyopathy and the urgent need for a re-evaluation of the indicators of patient survival. PMID- 1407807 TI - Choice of surgical procedure for prostatic surgery. PMID- 1407806 TI - Acute emphysematous cholecystitis: a case report and review of the literature. PMID- 1407808 TI - The physically handicapped children's program: a helping hand for children with serious health problems. PMID- 1407809 TI - Leiomyoma of the nipple. PMID- 1407810 TI - Prelude to research. PMID- 1407811 TI - Parse's theory and the multidisciplinary team: clarifying scientific values. PMID- 1407812 TI - Chaos and the totality perspective. PMID- 1407813 TI - Directions for nursing theory development in the 21st century. AB - The development of the discipline of nursing has gone through four stages: theorizing, developing a syntax, concept development, and philosophical debate. These stages helped in shaping the characteristics of the discipline as a human science, a practice science, a science with social goals to empower nurses to provide effective and quality care, and one in which gender differences and the need for understanding minorities are areas of primary concern. Further theoretical development in the discipline will be driven by population needs and will be characterized by reaching out to meet the integrative and interdisciplinary nature of these needs. Sources of theories of the future are practice, theory and research. It is anticipated that two models will evolve to guide the development of phenomenon-driven theories in the future and that third generation theorists will utilize these models. PMID- 1407814 TI - The overview effect: the impact of space exploration on the evolution of nursing science. AB - The purpose of this article is to explore the overview effect, an experience evoked by space travel that has the capacity to transform all patterns of human existence and evolution toward greater potentials in human diversity and creativity. As nurses migrate with humanity into the solar system and beyond, they will experience the overview effect. The core components of the effect include changed perceptions of space, time, sound, and weight which have the potential to transform the evolution of nursing science. Nursing paradigms will encompass a view of humanity as integral with an infinite evolutionary universe. After generations of living in space in a diversity of new environments, the physical body will undergo radical changes, and the meaning of health will be transformed. The article concludes with a discussion on the parallels between Rogers' science of unitary human beings and the overview effect. PMID- 1407815 TI - Nursing theory as a base for a computerized nursing information system. AB - This article illustrates how nursing theory can be used in a computerized nursing information system (CNIS). Before development of such a system can begin, data relationships must be specified so that: (a) the relationships are specific enough to support a computerized relational base and (b) the resultant information can support nursing science. Both goals were achieved through three interrelated processes: (a) validation of a practice model based on Orem's self care deficit nursing theory, (b) classification of clinical data into theory related categories, and (c) establishment of data relationships to yield meaningful information. PMID- 1407816 TI - The Roy Adaptation Model and care of persons with Alzheimer's disease. AB - This article uses current nursing literature to examine the congruence of the care of patients with Alzheimer's disease (AD) with the Roy adaptation model. In relating concepts of the Roy model to the care of patients with Alzheimer's disease, it was found that ineffective coping responses can be used to describe disease-related disruptive behaviors. The degenerative disease process would result in the impairment of focal stimuli, such as memory and personality. Because focal stimuli are progressively impaired, the goal of nursing using the Roy model would be to promote adaptive responses through manipulation of the contextual stimuli, the patient's environment. Nursing literature describing positive patient outcomes following environmental interventions suggests that the Roy adaptation model could be very valuable in directing nursing research and devising nursing care strategies for patients with Alzheimer's disease. PMID- 1407817 TI - Instrument development and the measurement of unitary constructs. AB - This article initiates needed dialogue on the development of instruments to measure unitary constructs. The concept of measurement is explored and current measurement in Rogerian research is considered in light of the issues raised in the discussion. The human field - environmental field relationship is presented as the clinical practice area serving as the basis for the development of a unitary instrument that purports to measure field pattern. The instrument entitled Mutual Exploration of the Healing Human Field - Environmental Field Relationship is offered as a beginning effort in constructing an instrument that measures a unitary phenomenon. Rogerian scholars are provided with the challenge to continue the debate regarding the whole field of measurement and the development of unitary tools. PMID- 1407818 TI - Moving beyond the barrier reef. PMID- 1407819 TI - Critical theory as a framework to enhance nursing science. PMID- 1407820 TI - Nutrition and cardiovascular disease--a brief review of epidemiological studies in Japan. PMID- 1407821 TI - Diet, nutrition and cancer in Japan. AB - A number of epidemiological and experimental studies have revealed that dietary habits and nutrition are one of the major risk factors for cancer. Dietary habits and nutrition are related to cancer in various ways and many factors are involved in the development of cancer. These include large intakes of salted foods and pickled vegetables, and too low intakes of fresh vegetables and fruits which are known to be major risk factors for stomach cancer. A large intake of green-yellow vegetables is known to be a protective factor against cancer of the stomach, lung and some other sites. In Japan the westernization of dietary habits and nutrition may have contributed to the changes in the mortality of several kinds of cancers which have been observed in Japan in recent years. Further improvements of dietary habits and nutrition intake are important and will be effective for primary prevention of cancer. PMID- 1407822 TI - Nutritional factors and cellular immune responses. AB - Nutritional factors affect the immune response to infection and cancer in the elderly as well as young children. We studied the effects of lower and higher intake of food or nutrients on the immune cells of macrophage-lymphocytes series in the lung of rats. In rats of all ages taking voluntary exercise, a well balanced diet that contains adequate protein (20-40%) is crucial for maintenance of high levels of immune response. In addition, extra amounts of vitamins A and E activated the function of alveolar macrophages, which are probably stimulated by fat soluble vitamins coming into the lung via the lymphatic route from the intestine, and will be especially important in preventing pulmonary infection and cancer. PMID- 1407824 TI - Achievement of school lunch system for the promotion of health of children in Japan. AB - In Japan, the modern school lunch system was improved after the establishment of the school lunch law in 1954, and now over 98% of boys and girls in primary schools and over 85% of junior high school pupils have lunch at their schools. In this report, the beneficial effect of this system is pointed out. This system contributes to an improvement of the physical condition of these children and it is very effective for improving the relationship between teachers and children. Knowledge concerning food, nutrition and food hygiene has also improved. PMID- 1407823 TI - Nutrition for the young--its current problems. AB - The prevailing life style in Japan has been westernized and highly industrialised. This inevitably has bad effects on nutrition and the eating pattern of youth. These ill effects may be summarized as follows, 1) lack of daily physical activities, 2) an increasing number of working mothers, 3) irregular timing of food intake, 4) an increasing intake of energy in the form of fat, 5) increasing consumption of processed foods ready for eating, 6) lack of integrated management systems such as health education programs against atherogenic risk factors. These changes have resulted in increasing atherogenic risk factors among young people. It is necessary to study the present risk factors and their relation to prevailing life styles and to organize a follow-up system for surveillance of risk factors. PMID- 1407825 TI - Nutritional factors for longevity in Okinawa--present and future. AB - Several factors, such as environment and heredity, are presumed to be related to longevity. Of these nutrition is believed to function as a regulatory factor. Okinawa prefecture is well known as the leading area for longevity in the world. We therefore examined present and past nutrition records together with the background of all the 88 centenarians (18 male, 70 female) who are living in Okinawa in 1991. Their leading occupation was agriculture, and they were in work until the 8th decade. They took rice or potato as carbohydrate with abundant vegetables and vegetable protein or fish protein. Although they did not take a rich diet it was well balanced, and was assumed to be related to longevity because of the decreased incidence of atherosclerosis; together with a good genetic background, suggested by the accumulation of longevity in their siblings. PMID- 1407826 TI - Nutrition for the Japanese elderly. AB - The present paper examines the relationship of nutritional status to further life expectancy and health status in the Japanese elderly based on 3 epidemiological studies. 1. Nutrient intakes in 94 Japanese centenarians investigated between 1972 and 1973 showed a higher proportion of animal protein to total proteins than in contemporary average Japanese. 2. High intakes of milk and fats and oils had favorable effects on 10-year (1976-1986) survivorship in 422 urban residents aged 69-71. The survivors revealed a longitudinal increase in intakes of animal foods such as eggs, milk, fish and meat over the 10 years. 3. Nutrient intakes were compared, based on 24-hour dietary records, between a sample from Okinawa Prefecture where life expectancies at birth and 65 were the longest in Japan, and a sample from Akita Prefecture where the life expectancies were much shorter. Intakes of Ca, Fe, vitamins A, B1, B2, C, and the proportion of energy from proteins and fats were significantly higher in the former than in the latter. Intakes of carbohydrates and NaCl were lower. PMID- 1407827 TI - Food policy for health in Japan. AB - In this half century, dietary habits in Japan have greatly changed and there is some confusion about what is healthy. In this report the causes of the confusion are analysed. To establish a healthy and normal dietary life, the recommendations for the public were considered from the various standpoints. There have been great changes in economic and social factors, and in supply and availability. Consumers rate convenience, diversity, good taste, healthiness, and "fashionableness" as important. To create a new food culture, the following three points would become the base; 1. It is necessary for each of us to have a sense of responsibility for our eating habits and our health. 2. We must cooperate with family and friends to work for the creation of an abundant and enjoyable dining table. 3. We have reached the stage in our dining culture where we must think not about what to eat, but how to eat, what conduct we should use when eating, and about our awareness of eating and what we are eating. PMID- 1407828 TI - Nutrition: the global challenge. PMID- 1407829 TI - A message from WHO: towards building a new health paradigm in the 21st century. PMID- 1407830 TI - International cooperative study on the relationship between dietary factors and blood pressure: a preliminary report from the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The CARDIAC Cooperative Study Research Group. AB - 1. To investigate the epidemiological relationship of dietary factors to blood pressure (BP) and major cardiovascular diseases, we carried out the international cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, which so far involves 48 centers in 20 countries as of August 1991. From each population, 100 men and 100 women aged 50-54 years were randomly selected for BP measurement, 24-h urine collection, blood tests, and medical interview. Various biological markers of diets from urine and blood were analyzed centrally in the Izumo CARDIAC center. 2. Cross center analysis using simple linear regression revealed strong significant correlations of body mass index (BMI) to systolic BP (SBP; p < 0.01) and diastolic BP (DBP; p < 0.001) in men. 24-h urinary sodium (Na) excretion in men also showed significant correlations with SBP (p < 0.05) and DBP p < 0.05) even after controlling for the effect of BMI (SBP; p < 0.05, DBP; p < 0.05). 3. Within center analysis using multiple linear regression implied that BMI and Na strongly adversely affect BP, whereas magnesium may have beneficial influence on BP. 4. Multicolinearities among 24h urinary sodium, calcium, and urea nitrogen were noted in men. PMID- 1407831 TI - Trends in national nutritional survey of Japan. AB - The nutritional status of the Japanese has been measured and evaluated annually on a nationwide scale since the first National Nutrition Survey was carried out in 1946. Changes in dietary intake levels could thus be monitored systematically at a national level. According to the results observed, the whole 50 years of the postwar period can be divided into three stages in terms of dietary intakes and their postulated health outcome. Although it has certain limitations for the purpose of analysis the survey has performed a remarkable role in throwing light upon the general trends and current status of nutrition in Japanese populations and thereby enabling a successful nutritional policy to be established. PMID- 1407832 TI - Nutritional improvement, cardiovascular diseases and longevity in Japan. AB - 1. Nutritional conditions have improved remarkably for the past 40 years in Japan; major improvements are increases in protein intake (69.7 in 1955 to 79.2g/day per capita in '88), and fat intake (20.3 in '55 to 58.3 g/day per capita in '88), both of which are significantly related statistically to the gradual reduction of stroke mortality (r = -0.74, not significant; r = -0.78, p < 0.05) and to a remarkable extension of average life span (r = 0.91, p < 0.01; r = 0.98, p < 0.001) in the Japanese. 2. Average heights of 12-year old male and female children, correlating significantly with these nutritional improvements, are significantly positively correlated with average life spans (men and women respectively; r = 0.97, p < 0.001). 3. Thus, general nutritional improvements among the Japanese are regarded as the major contributory factor to the recent achievement of top-ranked position for longevity in the world. PMID- 1407833 TI - PPS update. PMID- 1407834 TI - The new careers in nursing informatics. PMID- 1407835 TI - Anesthesia-related liability. PMID- 1407836 TI - Washington, DC: fall 1992. PMID- 1407837 TI - Staffing nurses according to episodic census variations. PMID- 1407838 TI - Compensation: what influences workers' sense of values? PMID- 1407839 TI - An effective PCA documentation tool. PMID- 1407840 TI - Implementing a multidisciplinary approach to discharge planning. PMID- 1407841 TI - Patient is discharged--but still in the bed! PMID- 1407843 TI - Personalized care in a standardized world. PMID- 1407842 TI - Integrating a "plan of care" into documentation systems. PMID- 1407844 TI - Developing a labor and delivery patient classification system. PMID- 1407846 TI - Who's minding the children? PMID- 1407845 TI - Upgrading critical care nursing assistant skills. PMID- 1407847 TI - Shift coordinators dispel myths. PMID- 1407848 TI - Caring behaviors in nursing management relationships. PMID- 1407849 TI - Maintaining a policy review system. PMID- 1407850 TI - A "burning issue": a nursing administrator's nightmare. PMID- 1407851 TI - Development of clinical coordinator role. PMID- 1407852 TI - Application of change theory to a clinical problem. PMID- 1407853 TI - Dear new assistant nurse manager. PMID- 1407854 TI - OSHA overdoes a good thing. PMID- 1407855 TI - Electronic claims transmission: the "fourth party" factor in dentistry. PMID- 1407856 TI - Management of vertical root fracture in endodontically treated teeth. AB - Vertical root fracture is a common complication during and after endodontic treatment. The condition is often difficult to diagnose and treat. Management of the fracture usually represents a challenging dilemma that requires various techniques. PMID- 1407857 TI - Dental students' knowledge of HIV-related matters. PMID- 1407858 TI - Survey of post procedures. AB - Methods used to restore endodontically treated teeth have changed over the last few years. The traditional standard of using a cast-gold post and core for all endodontically treated teeth has been questioned in the literature. The following is a report of a survey that the authors conducted to determine if there is a discrepancy between research and clinical practice. PMID- 1407859 TI - Caveat preparator: maxillary second bicuspid root invaginations. AB - Seventy-five percent of maxillary second bicuspids have a single pulpal canal. The remainder present dual canals with one or two associated apical orifices and proximal root concavities. This latter phenomenon may well lead to root perforations when placing posts. The following case documents such an occurrence. PMID- 1407861 TI - NIH backs Rochester study of lasers and tooth decay. PMID- 1407860 TI - Code of ethics. PMID- 1407862 TI - Stony Brook expands care of HIV-positive patients. PMID- 1407863 TI - Keeping pace with a changing profession. PMID- 1407864 TI - Radioiodine therapy for thyrotoxicosis. PMID- 1407865 TI - Abstracts of the British Nuclear Medicine Society Autumn Meeting. Plymouth, 7-8 November 1991. PMID- 1407866 TI - Alphabet soup--BNMS, ICSC, SAC et al. PMID- 1407867 TI - Recent changes in UK legislation and the licensing of radiopharmacies. AB - The implications of the recent loss of Crown Immunity to radiopharmacy in the NHS are reviewed. The options available are that the preparation of radiopharmaceuticals within a hospital will either be under the control of a pharmacist or be an activity licensed as 'Specials' manufacture. In the latter case the requirements for inspection by the Medicines Control Agency, the fees payable and the need for involvement of a pharmacist are reviewed. The requirements for the grant of a Specials Manufacturing Licence are presented in some detail. Reference is made to established and published sources of guidance, official and otherwise. Consideration is given to: staffing and personnel, open and closed procedures, environmental standards, handling of blood products, use of isolators, quality control and quality assurance, licensed and unlicensed materials, sterility testing, broth transfer tests, environmental monitoring and documentation. PMID- 1407868 TI - Lacrimal scintigraphy in the diagnosis of epiphora. AB - The value of lacrimal scintigraphy in the assessment of nasolacrimal duct obstruction was determined by comparing the results with syringing in 67 patients (83 eyes). As expected, of 28 lacrimal drainage systems which were obstructed on syringing, 23 (82%) had abnormalities of tear drainage on scintigraphy. However, in 55 lacrimal drainage systems that were patent on syringing, 19 (35%) were normal, but in 36 (65%) abnormalities not apparent on syringing were detected on scintigraphy. Thus scintigraphy is a very useful technique in the assessment of nasolacrimal duct obstruction particularly in systems patent on syringing. Since the site of obstruction can be determined, lacrimal scintigraphy can facilitate the planning of the appropriate surgery. PMID- 1407869 TI - Vertebral metastases and an equivocal bone scan: value of magnetic resonance imaging. AB - To assess the value of magnetic resonance imaging (MRI) in the investigation of patients with suspected but nonproven vertebral metastases 45 consecutive patients referred in a 6 month period with known primary malignancy and back pain in whom an isotope bone scan was reported as equivocal were studied. All patients had abnormal isotope uptake localized to the spine. Twelve patients were shown to have bony metastases on plain X-ray. In the remainder, where X-rays showed normal or benign appearance, MRI of the spine was offered. Twenty-four patients underwent MRI examination which showed vertebral metastases in 11 cases. Magnetic resonance imaging is shown to be a useful, noninvasive, complementary investigation for evaluation of patients known to have malignant disease and suspected of having vertebral metastases on bone scintigraphy. PMID- 1407871 TI - 67Ga uptake at sites of heterotopic calcification: a report of three cases. AB - Heterotopic calcification occurs commonly in spinal cord injured patients and following joint trauma or surgery. 99Tcm-methylene diphosphonate is useful in the detection of these lesions, many of which are subclinical. Three patients are presented with heterotopic calcification, one with severe hypoxic encephalopathy and two following major trauma. Intense 67Ga uptake within areas of heterotopic calcification was noted in all three patients. Two of the patients also underwent 99Tcm-methylene diphosphonate bone scanning and showed uptake of the bone agent corresponding to the areas of 67Ga uptake. In predisposed patients, heterotopic calcification should be considered in the differential diagnosis of a focal area of 67Ga uptake. PMID- 1407870 TI - A dual-isotope method for studying protein kinetics in pleural effusions in humans. AB - A method is described for studying protein kinetics in pleural effusions in humans. In 15 patients with pleural effusions from a variety of causes, protein inflow was monitored by measuring the rate of appearance in the effusion of the plasma protein transferrin, radiolabelled in vivo by intravenous injection of 113InmCl3. Protein outflow was measured from the rate of appearance in the blood of intrapleurally administered 125I-albumin. Compartmental analysis has been used to determine rate constants k(in) and kout for the movement of labelled proteins into and out of the effusion, respectively. The mean value of k(in) for 15 patients was 9.4 x 10(-4) h-1 (range 2.2-21.4). The mean value of kout in the same patients was 28 x 10(-4) h-1 (range 6-68). Using appropriate assumptions where necessary, the absolute transfer rates of albumin and transferrin were also estimated. For albumin, the mean rate of outflow was 66 mg h-1 (range 27-158), compared to mean estimated inflow of 133 mg h-1 (range 36-381). Protein inflow was highest in a case of metastatic ovarian carcinoma with pleural and peritoneal seedlings, indicating high vascular permeability. Protein outflow was very low in a case of mesothelioma, suggesting severely impaired lymphatic drainage. The technique may prove to be a useful tool for studying mechanisms resulting in the formation of malignant and nonmalignant pleural effusions, and may also be useful for studying the effects of putative therapeutic intervention. PMID- 1407873 TI - Visualization of myocardial infarction 6 h after injection of 111In-antimyosin antibodies using a blood pool subtraction technique. AB - 111In-antimyosin antibodies are capable of visualizing myocardial infarction (MI). Because of slow blood clearance, images are usually recorded 24 or 48 h postinjection. In this pilot study, a blood pool subtraction technique, which makes it possible to visualize MI 6 h postinjection, is validated. Twenty-five patients with proven MI (16 anterior, 9 inferior) were imaged a few minutes, 6 and 24 h after an injection of 111 MBq 111In-labelled antimyosin antibodies. Three planar views are obtained each time. Using software which performs the geometric registration, the grey level normalization and the subtraction of images, the blood pool image (obtained a few minutes postinjection) is subtracted from the 6 h image. The resulting image is the blood pool corrected 6 h image. The 24 h images and the blood pool corrected 6 h images were interpreted blindly and the number of correct, incorrect and impossible MI localizations was counted. The number of correct localizations is 19/25 for the standard 24 h images and 22/25 for the blood pool corrected 6 h images. Then, with this blood pool subtraction method, it is possible to visualize MI 6 h postinjection. This has to be taken into account when discussing the role of antimyosin scintigraphy in the management of patients with MI. PMID- 1407872 TI - Hydroxamamide as a chelating moiety for the preparation of 99Tcm radiopharmaceuticals (I). AB - Hydroxamamides contain a nitrogen and an oxygen as donor atoms, and can be synthesized by the simple reaction of nitriles with hydroxylamine. Benzohydroxamamide (BHam) was investigated as a new ligand for 99Tcm. The yield of the 99Tcm-BHam complex was determined by thin-layer chromatography using cellulose strips. A high yield of the complex was obtained at room temperature over a wide pH range, even at BHam concentrations as low as 5 x 10(-7) M. Cellulose acetate electrophoresis indicated that the complex was uncharged. When the 99Tcm-BHam complex was injected into mice, it was cleared gradually from the blood by means of the hepatobiliary system with low urinary excretion. Uptake by the stomach and the spleen was low. These results demonstrate the high affinity of BHam for 99Tcm and the high stability of the 99Tcm-BHam complex. The hydroxamamide group may be a promising chelating moiety for designing new 99Tcm radiopharmaceuticals. PMID- 1407874 TI - Study of myocardial regional wall motion parameter's accuracy by software perfusion phantom. AB - Gated perfusion myocardial scintigraphy permits simultaneous evaluation of perfusion as well as regional contractile function of the left ventricle. Fourier analysis of regional myocardial spatial movement with respect to the myocardial geometric centre gives circular amplitude and phase profiles of ventricular contraction, in addition to regional maximum activity that represents an index of perfusion. To introduce such combined perfusion-contraction analysis the accuracy of the indices mentioned above should be evaluated for different doses of radioactivity typically administered to a patient. A mathematical software phantom, consisting of a half circularly profiled ring activity embedded in uniform background activity and noise generated by a Poisson-shaped random number generator, was constructed and used for this purpose. A 64 x 64 matrix and sequence of 16 frames per study was used. The maximum number of counts per pixel ranged from 10 to 100, simulating low count thallium and high count rate Tc-MIBI gated studies. The relative standard error analysis (R.S.E.) with a 95.5% confidence level for a thallium type of 10 counts per pixel study exceeded 11%, while it reached acceptable values below 3% for studies with 60 and more counts per pixel. These results indicate that high count rate gated technetium-MIBI myocardial perfusion studies could also be used for reliable left ventricular regional wall motion evaluation. PMID- 1407875 TI - 99Tcm-HMPAO-labelled white blood cell scanning for the detection of carditis in the differentiation of rheumatic fever and inactive rheumatic heart disease in children. AB - Myocardial imaging with 99Tcm-hexamethylpropylene amineoxime (HMPAO)-labelled white blood cells (Tc-WBC) was used to detect carditis and differentiate rheumatic fever (RF) and inactive rheumatic heart disease (IRHD). Ten cases of RF and 15 cases of IRHD were studied, and the results revealed 60% (6/10) of the cases of RF with carditis, but none of the cases (0/15) of IRHD with carditis. There was significant difference (P less than 0.05, by Fisher's test) between RF and IRHD. In our preliminary conclusion, Tc-WBC heart scanning may be a noninvasive method for evaluating the existence of carditis in cases of RHD and in the differentiation of RF and IRHD. PMID- 1407876 TI - Nuclear medicine in otolaryngology. PMID- 1407877 TI - Estimating the time of death in stillborn fetuses: II. Histologic evaluation of the placenta; a study of 71 stillborns. AB - OBJECTIVE: To determine whether placental histologic examination is useful for predicting the approximate time of death in stillborn fetuses. METHODS: Hematoxylin and eosin slides of 71 placentas of stillborns with accurately timed deaths were studied retrospectively. Fifty-one placentas (learning set) were used to develop proposed histologic criteria for the timing of fetal death, which were then tested in the remaining 20 placentas (test set). RESULTS: Among 15 histologic variables assessed in the learning set, three features appeared to correlate well with specific death-to-delivery intervals: 1) villous intravascular karyorrhexis (6 or more hours); 2) vascular lumen abnormalities of stem villi, including fibroblast "septation" and total luminal obliteration (multifocal, 2 or more days; extensive, 2 or more weeks); and 3) extensive fibrosis of terminal villi (2 or more weeks). When the placentas in the test set were evaluated using the three histologic criteria, 18 of 20 cases were classified correctly with respect to the approximate time of fetal death. CONCLUSIONS: Placental histologic examination seems to be useful for determining the approximate time of death in many stillborn fetuses. PMID- 1407878 TI - Estimating the time of death in stillborn fetuses: III. External fetal examination; a study of 86 stillborns. AB - OBJECTIVE: To determine how accurately the time of fetal death can be predicted from the extent of external maceration in a stillborn fetus. METHODS: Autopsy photographs of 86 stillborns with well-timed deaths were studied retrospectively. Sixty randomly chosen fetuses (learning set) were assessed unblinded to develop proposed gross criteria for timing fetal death; 26 fetuses (test set) were then randomly and blindly assessed to test the accuracy of the proposed criteria. RESULTS: The two earliest changes in the learning cases were areas of desquamation measuring at least 1 cm in diameter and brown-red discoloration of the umbilical cord stump. Both changes occurred primarily in fetuses with death to-delivery intervals of 6 or more hours. Other early changes included desquamation involving the face, abdomen, or back (12 or more hours); desquamation involving 5% or more of the body surface (18 or more hours); brown skin discoloration (24 or more hours); and a moderate or severe extent of desquamation (24 or more hours). The only late change that correlated with a specific duration of intrauterine retention was mummification (2 or more weeks). When the 26 test fetuses were randomly and blindly assessed using these gross criteria, 18 (69%) were classified correctly with respect to the approximate time of fetal death. CONCLUSION: External fetal examination is useful for estimating the time of death in many stillborns; this information may be helpful when a complete autopsy cannot be performed. PMID- 1407879 TI - Fetal DNA in uterine vein blood. AB - OBJECTIVE: To investigate whether the ratio of fetal cells in the maternal circulation differs before and after the blood passes through the maternal lung. METHODS: We performed polymerase chain reaction-based Y-sequence analysis of DNA derived from antecubital vein blood obtained before and 2 hours after cesarean delivery, and from uterine vein blood obtained during cesarean of 14 women carrying male fetuses. RESULTS: Fetal DNA was detected in 17 tested specimens and, as estimated by comparison with parallel dilution series, the fetal-maternal DNA ratio was 1:10(5) to 1:10(6). However, there was no significant difference in the amount of Y-chromosomal DNA detectable between uterine vein blood and peripheral blood after polymerase chain reaction and Southern hybridization. In DNA derived from peripheral blood after delivery, the intensity of Y-specific fetal DNA sequences was also not significantly increased. CONCLUSION: Our results argue against the often-stated hypothesis of different ratios of fetal to maternal DNA in the uterine vein versus peripheral blood, and indicate that even delivery does not seem to increase the flow of fetal cells into the maternal circulation. PMID- 1407880 TI - Effect of intra-amniotic administration of Exosurf in preterm rabbit fetuses. AB - OBJECTIVE: Currently, treatment of respiratory distress syndrome (RDS) of the preterm newborn incorporates exogenous surfactant administration. Because fetuses make breathing motions, we proposed that intra-amniotic administration of an exogenous surfactant, Exosurf, to the preterm rabbit fetus results in uptake of Exosurf into the lungs and improves pulmonary mechanical properties compared with post-delivery treated and untreated litter mates. METHODS: Ten preterm rabbit fetuses were used in a labeling study. A mixture of iron dextran and Exosurf was given in utero, and the minimum dose required to assure delivery of the mixture into the distal airways was 5 mL. In a lung function study, 30 rabbit pups received either 5 mL Exosurf in utero, 0.2 mL Exosurf post-delivery, or no treatment. Pressure-volume curves, opening pressures, and lung volumes at 50 cm H2O were compared among the three groups. RESULTS: Those rabbit pups receiving Exosurf either in utero or after delivery had significantly better pressure volume relationships (P less than .001) and lower opening pressures (P less than .005) than the rabbit pups with no treatment. There were no differences between the animals treated intra-amniotically and post-delivery. CONCLUSIONS: Intrauterine administration of exogenous surfactant results in uptake of the surfactant solution into the lungs and alters the pulmonary characteristics of the preterm rabbit pup. Potential adverse effects of this means of surfactant administration must be evaluated further. Intrauterine surfactant delivery may provide an additional means of RDS prophylaxis in the antepartum period. PMID- 1407881 TI - Seroprevalence and risk factors for hepatitis C virus antibody in pregnant women. AB - OBJECTIVE: To better understand hepatitis C viropathies and seroprevalence by performing an epidemiologic analysis of pregnant women seropositive for antibody against hepatitis C. METHODS: We studied 1013 consecutive obstetric patients at Parkland Memorial Hospital who gave informed consent for detailed interviews and serotesting. Sera were analyzed for antibody to the hepatitis C virus using both C100-3 and RIBA-4 assays. Neonatal assessment was carried out in the immediate postpartum period. RESULTS: Hepatitis C antibody was detected in 2.28% (N = 23) of the 1005 women in whom analysis was completed. Factors associated with seropositivity included intravenous (IV) drug use, sexually transmitted diseases, hepatitis B infection, maternal age greater than 22.5 years, increased parity (eg, greater than 2.1), history of transfusion, and three or more different lifetime sexual partners or a sexual partner who used IV drugs. Maternal and neonatal outcome was not different between hepatitis C antibody-positive and negative groups. CONCLUSIONS: Epidemiologic data are consistent with sexual and parenteral modes of transmission. Women with hepatitis C antibody did not have excessive perinatal complications compared with antibody-negative women. A model protocol and cost analysis for screening pregnant women for hepatitis C infection are presented. However, routine screening for hepatitis C is not advocated. PMID- 1407882 TI - Outcome of treated pregnancies in women with antiphospholipid syndrome: an update of the Utah experience. AB - OBJECTIVE: To determine the outcome of treated pregnancies in women with well characterized antiphospholipid syndrome. METHODS: We reviewed 82 consecutive pregnancies in 54 women with antiphospholipid syndrome who were treated during pregnancy with the following: 1) prednisone and low-dose aspirin; 2) heparin and low-dose aspirin; 3) prednisone, heparin, and low-dose aspirin; or 4) other combinations of these medications or immunoglobulin. RESULTS: The overall neonatal survival rate was 73%, excluding spontaneous abortions, but treatment failures (fetal and neonatal deaths) occurred in all treatment groups. Patients with successful treated pregnancies had fewer previous fetal deaths than those with unsuccessful treated pregnancies. There were no significant differences in outcome among the four treatment groups. Preeclampsia and fetal distress occurred in half of all pregnancies, and fetal growth impairment occurred in nearly one third. Preterm delivery due to maternal or fetal indications was required in 37% of the pregnancies. Four pregnancies were also complicated by postpartum thrombosis during treatment. CONCLUSIONS: Pregnancy in women with antiphospholipid syndrome appears to be improved by treatment, but fetal loss may occur despite treatment. Preeclampsia, fetal distress, fetal growth impairment, and premature delivery are common. Because of the clinically significant risk of thrombotic episodes, thrombosis prophylaxis should be considered in these patients. PMID- 1407883 TI - Cost-benefit analysis of autologous blood donation in obstetrics. AB - OBJECTIVE: To determine whether there are predictors of peripartum transfusion, other than placenta previa, that identify a population of pregnant women whose risk of transfusion is high enough to justify antepartum autologous blood donation. METHODS: Using an established perinatal data base, we studied 14,267 consecutive term deliveries without placenta previa. Univariate and multivariate analyses were performed to assess ten predictors of peripartum transfusion that might reasonably be detected in the antepartum period. Costs were calculated for a hypothetical autologous blood donation program to prevent transfusion-related infection. RESULTS: Red-cell transfusion was used in 150 deliveries (1.1%). A total of 424 units was transfused (2.9 per 100 deliveries). Four risk factors were significantly (P less than .05) predictive of peripartum red-cell transfusion: preeclampsia (adjusted odds ratio 3.69), multiple gestation (2.82), elective cesarean (1.71), and nulliparity (1.51). Controlling for these, there was no association between transfusion and previous postpartum hemorrhage, previous cesarean with trial of labor, prior abortions, induction of labor, or ethnic group. A hypothetical antepartum blood donation program restricted to patients with three or more risk factors would cost $32,800-130,700 per case to prevent transfusion-related hepatitis and $26,000,000-78,000,000 per case to prevent human immunodeficiency virus infection. CONCLUSION: In obstetric patients without placenta previa, the need for peripartum red-cell transfusion cannot be predicted with sufficient accuracy to justify the costs of antepartum autologous blood donation. PMID- 1407884 TI - The prediction of "controlled" uterine rupture by the use of intrauterine pressure catheters. AB - OBJECTIVE: To determine whether uterine activity, assessed by either fluid-filled or solid pressure catheters, changes with uterine incision at cesarean delivery. METHODS: Uterine activity was recorded continuously during low transverse cesarean delivery in ten parturients using fluid-filled pressure catheters and in ten women with solid pressure catheters. Visual analyses were performed of the last 30 minutes of uterine recording before uterine incision and of the period after incision; the analyses were then compared within and between the catheter groups for mean uterine tone and contraction amplitude, frequency, and duration. Oxytocin use, anesthesia method, mean gestational age, birth weight, length of labor, duration of monitoring, and uterine incision-to-delivery time were compared between the groups. RESULTS: All obstetric end points were similar in both catheter groups except for a higher mean birth weight in the solid-catheter group. The mean (+/- standard deviation) duration of post-incision monitoring was 4.7 +/- 0.94 minutes. After uterine incision, mean tone and contraction amplitude were unchanged, whereas mean contraction frequency and duration decreased significantly. CONCLUSIONS: Though intrauterine monitoring was brief, this model allows a unique view of "controlled" uterine rupture. Spontaneous uterine rupture may evolve more gradually; however, neither catheter type would be likely to aid its early recognition. PMID- 1407885 TI - Effects of digital vaginal examinations on latency period in preterm premature rupture of membranes. AB - OBJECTIVE: To compare the clinical outcome in patients with preterm premature rupture of membranes (PROM) who had a sterile speculum examination with those having a digital vaginal examination. METHODS: We studied 271 singleton pregnancies complicated by preterm PROM from the Memorial Medical Center of Long Beach Perinatal Outreach program that met the criteria for expectant treatment from January 1986 to April 1990. Patients were not included in the study if they had multiple gestations, cerclage, advanced labor, or any indication for delivery on admission (eg, mature lung profile, chorioamnionitis). All subjects were maternal transports to our tertiary care facility and were managed similarly by our perinatal group. The women were questioned as to whether a digital vaginal examination had been performed before transport. Latency period and other obstetric characteristics were then compared. The latency period, defined as days from rupture of membranes until active intervention was initiated or labor began spontaneously, was also stratified by gestational age. RESULTS: One hundred twenty-seven subjects had a digital vaginal examination and 144 had a sterile speculum examination. A significantly (P less than .0001) shorter mean latency period (2.1 +/- 4.0 versus 11.3 +/- 13.4 days) was found in those who had a digital vaginal examination. In addition, a shorter latency period was noted for each gestational age. No difference in uterine activity or cervical dilatation and effacement was noted between the groups on admission. CONCLUSION: Digital vaginal examinations performed on patients whose pregnancies are complicated by preterm PROM appear to shorten significantly the latency period. PMID- 1407886 TI - Five-year outcome of preterm and very low birth weight infants: a comparison between maternal and neonatal transport. AB - OBJECTIVE: To determine the 5-year outcome of very low birth weight infants referred to tertiary perinatal centers. METHODS: This study was part of a Dutch national collaborative survey of 1338 newborn infants younger than 32 weeks' gestation and/or with a birth weight of less than 1500 g born in 1983. Comparisons were made between maternal transport to university hospital perinatal centers versus delivery in local hospitals, and between neonatal transport to these centers versus treatment in local hospitals. For the 252 survivors meeting the entry criteria for this part of the study, adverse outcome at 5 years of age was evaluated by logistic regression analysis, including 26 perinatal risk factors as confounding variables. Outcome variables were disabilities and handicaps at 5 years as defined by the World Health Organization. RESULTS: There were no differences in handicaps and disabilities between infants born after maternal transport and those born in local hospitals. Handicaps and disabilities in neonates transported versus those treated in local hospitals were also not statistically different despite selection bias. CONCLUSIONS: The previously reported decrease in neonatal mortality risk after maternal transfer is not accompanied by an increased risk of adverse outcome for the survivors. In threatening very preterm delivery, maternal transport to a tertiary center is recommended. PMID- 1407887 TI - Treatment-induced cyclic variations in serum lipids, lipoproteins, and apolipoproteins after 2 years of combined hormone replacement therapy: exaggerated cyclic variations in smokers. AB - OBJECTIVE: To study the long-term effect of cigarette smoking on cyclic variations in serum lipids, lipoproteins, and apolipoproteins following combined hormone replacement therapy. METHODS: One hundred eighteen healthy, early postmenopausal women were followed for 2 years in a randomized, placebo controlled study. Four treatment groups received estradiol, either sequentially combined with levonorgestrel (75 micrograms), medroxyprogesterone acetate (10 mg), or desogestrel (150 micrograms), or continuously combined with cyproterone acetate (1 mg). Two groups received placebo. Serum lipids, lipoproteins, and apolipoproteins were measured at well-defined times. Information on smoking habits was elicited by questionnaire. RESULTS: We found statistically significant cyclic variations in apolipoprotein A1 in the levonorgestrel group (6.7%; 95% confidence interval [CI] 1.1-12.7%) and the desogestrel group (7.4%; 95% CI 2.9 12.1%). The cyclic variations in high-density lipoprotein (HDL) cholesterol were highly statistically significant in the levonorgestrel group (24.9%; 95% CI 10.2 39.2%). When women from sequential regimens were combined, further analysis showed that smokers had significantly larger cyclic variations in HDL cholesterol (P less than .01) and apolipoprotein A1 (P less than .05) than non-smokers. CONCLUSIONS: Sequentially combined hormone replacement therapy produces cyclic variations in HDL cholesterol and apolipoprotein A1 for at least 2 years. In addition, cigarette smoking is associated with an exaggeration of the cyclic effect of treatment on these indices. PMID- 1407888 TI - Comparison of silastic rings and electrocoagulation for laparoscopic tubal ligation under local anesthesia. AB - OBJECTIVE: To compare objectively the pain associated with tubal occlusion by Silastic rings versus electrocoagulation during laparoscopic tubal ligation under local anesthesia. METHODS: Consecutive patients scheduled for laparoscopic tubal ligation under local anesthesia were randomized to Silastic rings (N = 50) or electrocoagulation (N = 52) as the method of tubal occlusion. Sterilization was performed under local anesthesia in a standard fashion. Bupivacaine 0.5% was used as the local anesthetic agent. Operative pain was measured based on intraoperative anesthesia requirements and a modified McGill pain questionnaire. This questionnaire was used to assess pain at 15 minutes, 1 hour, and 24 hours postoperatively. RESULTS: Demographics were similar for the two groups. Operative time was shorter in the Silastic-ring group (16.7 versus 21.8 minutes; P = .001), and this group also required less intraoperative anesthesia (P = .004). There were no statistical differences between the groups in self-reported pain intraoperatively or postoperatively. No patient in either group required antiemetics or pain medication in the recovery room. CONCLUSION: Silastic rings appear preferable to bipolar electrocoagulation for laparoscopic tubal sterilization under local anesthesia when long-acting local agents are used for tubal anesthesia. PMID- 1407889 TI - Abdominal wound closure using a running, looped monofilament polybutester suture: comparison to Smead-Jones closure in historic controls. AB - OBJECTIVE: To determine whether abdominal wound closure with a running, looped monofilament polybutester suture was as effective, inexpensive, and rapid as Smead-Jones closure using the same material. METHODS: Between April 19, 1990 and August 29, 1991, 154 patients undergoing major gynecologic surgery had wound closure using a running, looped monofilament polybutester suture. Controls were 154 patients undergoing similar surgical procedures in the 15 months immediately preceding the study period (January 5, 1989 to April 18, 1990) whose wounds were closed with 0 polybutester using the Smead-Jones technique. All patients received prophylactic cephalosporin antibiotic therapy and external pneumatic leg compression perioperatively. The subcutaneous tissues were not sutured after fascial closure, and the skin was closed with stainless-steel staples. There was no difference between the groups when compared by mean weight, mean ponderal index, number of previous abdominal operations, operative blood loss, or the use of chemotherapy or radiotherapy in the pre- or postoperative period. Both groups had similar rates of complicating medical conditions including insulin-dependent and non-insulin-dependent diabetes mellitus, hypertension, obstructive pulmonary disease, atherosclerotic coronary disease, or peripheral vascular disease. RESULTS: The use of a running closure with looped monofilament polybutester suture in the study patients resulted in a reduction in operating time when compared with controls. The rates of superficial separation and wound infection were similar in both groups. In the study group, there was one minor fascial separation and one wound dehiscence, which occurred when the running suture was inadvertently snipped during debridement of a superficial infection. CONCLUSION: Running closure with looped polybutester is an acceptable, inexpensive, and expeditious method of abdominal wound closure. PMID- 1407890 TI - Determinants of survival of surgically staged patients with endometrial carcinoma histologically confined to the uterus: implications for therapy. AB - OBJECTIVE: To determine the factors that influence the survival of patients with endometrial carcinoma histologically confined to the uterus. METHODS: Retrospective analysis was conducted of 262 surgically staged cases using multiple regression (Cox proportional hazards model). RESULTS: After excluding patients with clear-cell and serous tumors, which were adverse prognostic factors unrelated to any other variables, we found that survival was adversely affected by increasing stage, tumor grade and depth of myometrial invasion, cervical stromal and vascular space invasion by tumor, and increasing age. Tumor grade, myometrial invasion, and cervical involvement by tumor exerted their effects on survival as dichotomous rather than as ordinal variables. The greatest effect on survival was obtained by dichotomizing grade as grade 3 versus grade 1 or 2, myometrial invasion as invasion of more versus less than the inner third of the myometrium, and cervical spread as the presence versus absence of stromal invasion. The joint effect of the tumor-related prognostic factors was best expressed by constructing three risk groups consisting of patients with zero or one, two, and three or four risk factors. These risk groups were associated with 5-year survival rates of 97, 66, and 17%, respectively. After adjustment for risk factors, pelvic radiation did not affect survival significantly, although there was a trend toward improved survival of subjects with two risk factors who received pelvic radiation (70 versus 50% survival at 5 years). CONCLUSIONS: The number of tumor-related risk factors present is the best predictor of survival of patients with endometrial carcinoma confined to the uterus, and may provide the optimal basis for individualization of treatment. PMID- 1407891 TI - Epidural analgesia in labor and fetal hyperthermia. AB - OBJECTIVE: To assess the effect of epidural analgesia on fetal temperature in labor, contrasting intrauterine with oral thermometry. METHODS: Fetal skin and maternal uterine wall temperatures were measured with an intrauterine probe in 57 laboring women at term. Maternal oral temperatures were measured in the normal way by birth attendants unaware that their measurements would be examined. Maximum recorded fetal, uterine, and oral temperatures were compared. RESULTS: Epidural analgesia resulted in a significant fetal temperature rise compared with other methods of analgesia. Duration of epidural analgesia correlated with the fetal temperature (R = 0.44, P = .012). Oral thermometry underestimated fetal temperature in 95% of the studies. CONCLUSIONS: We estimate that 5% of fetuses reached a core temperature in excess of 40C in this study, all in association with epidural analgesia. We suggest that antipyretic measures be considered after 5 hours of epidural analgesia in ambient temperatures above 24C. PMID- 1407892 TI - Significance of cardiac activity on endovaginal ultrasound in very early embryos. AB - OBJECTIVE: To evaluate the significance of cardiac activity on endovaginal ultrasound in embryos up to 10 mm in size. METHODS: Ninety-six women with positive urinary pregnancy tests had vaginal probe ultrasound examinations at the first clinical visit. All had discernible embryos between 1-10 mm in greatest length. The presence or absence of discernible cardiac activity was recorded. None of the subjects had any antecedent bleeding. All were available for follow up until delivery or completion of a failed pregnancy. RESULTS: Seventy-four women had cardiac activity present at the initial study and 22 did not. Eighty one delivered healthy newborns and 15 had early pregnancy failure. All embryos that ultimately proved normal showed cardiac activity by the time they were 4 mm in size. However, absence of detectable cardiac activity in embryos of 3 mm or less was still associated with a 41% continuation rate. CONCLUSIONS: Cardiac activity is present in normal embryos before it can be detected on ultrasound. There are variations in the type and frequency of ultrasound equipment, maternal anatomical characteristics (obesity, coexisting fibroids, uterine version), and in the visual acuity of observers. Nevertheless, we conclude that in our hands, the absence of cardiac activity in embryos measuring 4 mm or more is reliably associated with embryonic death. In contrast, the lack of cardiac activity in embryos of 3 mm or less is nondiagnostic and may warrant follow-up study in 3-5 days. PMID- 1407893 TI - Short-term fetal heart rate variation, decelerations, and umbilical flow velocity waveforms before labor. AB - OBJECTIVE: To determine the value of computerized antepartum measurements of short-term fetal heart rate (FHR) variation and decelerations as a predictor of outcome, and to compare these with measurements of the umbilical artery flow velocity waveform. METHODS: Data were collected from 3563 high-risk patients for measurements of FHR variables (15,702 records) and outcome (intrauterine death or metabolic acidemia on delivery). Detailed analyses were made on 89 patients with one or more records in which short-term FHR variation was 3 milliseconds or less. Umbilical artery flow velocity waveforms were measured concurrently on 2441 occasions in 991 patients. RESULTS: More than half of the patients with FHR variation of 3 milliseconds or less were identified before 31 weeks. When short term FHR variation exceeded 3 milliseconds, there were no intrauterine deaths and only one instance of metabolic acidemia on cesarean delivery. When FHR variation fell below 2.6 milliseconds, 34% of the subjects had metabolic acidemia on cesarean or intrauterine death. The appearance or absence of decelerations was an unreliable guide to outcome. The correlation between FHR variation and the umbilical artery flow velocity waveform was low (r = 0.32). The population studied contained some patients without placental vascular disease or, in five with pre-eclampsia, without abnormal umbilical artery velocity waveforms but with grossly reduced FHR variation. CONCLUSION: Reduction in short-term FHR variation, as measured by computer, reliably predicts fetal outcome and is a more general measure of fetal well-being than are umbilical artery flow velocities. PMID- 1407894 TI - Reappearance of end-diastolic velocities in the umbilical artery following maternal volume expansion: a preliminary study. AB - OBJECTIVE: To determine the effects of maternal volume expansion on feto- and uteroplacental blood flow and neonatal outcome. METHODS: Seven women with pregnancies characterized by absent end-diastolic velocity in the umbilical artery were treated with bed rest, antihypertensive medication, and volume expansion (expanded group) and compared with seven similar cases treated with bed rest and antihypertensive medication (unexpanded group). RESULTS: In the expanded group, end-diastolic flow reappeared temporarily in all cases after volume expansion. The pulsatility index in the umbilical artery decreased from 2.69 (95% confidence interval [CI] 2.1-3.2) to 2.15 (95% CI 1.74-2.56) 24 hours after maternal volume expansion (P less than .001). All cases in the unexpanded group continued to demonstrate absent end-diastolic velocity. There was no significant difference between the groups with regard to birth weight, which was 773 g (95% CI 521-1025) in the expanded group and 724 g (95% CI 429-1019) in the unexpanded group (P = .76). The gestational age at delivery was not significantly different between the groups: 203 days in the expanded group (95% CI 195-211) and 207 days in the unexpanded group (95% CI 189-225) (P = .71). The overall survival rate was significantly better in the expanded group: five of seven, versus one of seven in the unexpanded group (P less than .05). CONCLUSIONS: These preliminary data suggest that it is possible to improve feto- and uteroplacental perfusion with maternal volume expansion. The results point toward an improvement in neonatal outcome. Randomized trials are necessary to confirm our observations. PMID- 1407895 TI - The significance of increasing umbilical artery systolic-diastolic ratios in third-trimester pregnancy. AB - OBJECTIVE: To evaluate the clinical significance of a marked increase in the systolic-diastolic ratios (S/Ds) of the umbilical artery (UA) Doppler velocity waveforms of third-trimester fetuses. METHODS: We evaluated 552 pregnancies at risk for placental insufficiency. Each patient had at least five successive weekly UA Doppler velocimetry studies between 32-42 weeks and a highest S/D within the normal range for gestational age. The S/D was considered markedly increased if it was at least 20% higher than the mean of four previous values. Clinical end points reviewed included mortality, fetal distress, 5-minute Apgar score below 7, metabolic acidosis, and neonatal intensive care unit (NICU) admissions for reasons other than prematurity. RESULTS: The S/Ds were normal in 478 patients and were markedly increased in 74. The two groups were similar in mean gestational age at testing and delivery and in the rates of fetal growth retardation and low 5-minute Apgar scores. The group without increased S/Ds had a higher mean birth weight and lower incidences of perinatal death, cesarean delivery for fetal distress, acidosis, and NICU admission. The overall sensitivity (43%), specificity (90%), positive predictive value (27%), and negative predictive value (95%) were similar to our previous experience in which we used a criterion of S/D above the 90th percentile. CONCLUSION: Marked increases in UA S/Ds, even if within an institutional "normal" range, may indicate a fetus at increased risk of compromise. PMID- 1407896 TI - Clinical evaluation of the NBD-PC fluorescence polarization assay for prediction of fetal lung maturity. AB - OBJECTIVES: 1) To examine a fluorescence polarization (FP) assay with an independent set of data that contained more cases of respiratory distress syndrome (RDS) than a previous study, 2) to determine whether the same reference ranges are applicable to infants born to diabetic women, and 3) to evaluate whether adding the lecithin-sphingomyelin ratio (L/S) would substantially improve the prediction of RDS among women with an intermediate FP value (between 0.26 0.289). METHODS: We identified 389 women who had FP analysis performed at the University of Washington Medical Center from February 1986 to October 1988 and who delivered within 3 days of amniocentesis. We reviewed the medical records of these women and their infants to extract information for our study. RESULTS: For FP values of 0.26 or greater, the sensitivity and specificity for prediction of RDS were 90.2 and 84.6%, respectively, compared with 100 and 82.0% in the previous study. For FP values of 0.29 or greater, the sensitivity and specificity were 62.8 and 94.2%, respectively (80.8 and 96.2% in the previous study). Among diabetics, an FP result below 0.26 was associated with the same low risk of RDS as among non-diabetics. Among the patients with FP between 0.26-0.289, the addition of L/S did not provide a clinically useful improvement in the prediction of fetal lung maturity. CONCLUSION: The NBD-PC FP assay can be used as the sole test of fetal lung maturity in most clinical circumstances. PMID- 1407897 TI - Urethral diverticula: evaluation by urethral pressure profilometry, cystourethroscopy, and the voiding cystourethrogram. AB - OBJECTIVE: To compare the value of urethral pressure profilometry with that of cystourethroscopy and the voiding cystourethrogram in the evaluation and management of urethral diverticula. METHODS: Twelve women with signs or symptoms of a urethral diverticulum were referred. The initial evaluation included cystourethroscopy and a voiding cystourethrogram. All then underwent urethral pressure profilometry. RESULTS: Nine of 12 patients had urethral diverticula, two had Skene duct cysts, and one had genuine stress incontinence. Both cystourethroscopy and voiding cystourethrography demonstrated diverticula in all patients who had them. Excision was the preliminary surgical plan in these women. Urethral pressure profilometry demonstrated a pressure depression or biphasic curve in all nine cases with diverticula. Stress incontinence was noted in one of these nine women. A biphasic curve was also noted in one woman with a Skene duct cyst and in the one who had genuine stress incontinence only. According to preset criteria for profilometry, excision was the planned operative procedure for all. CONCLUSIONS: Cystourethroscopy and voiding cystourethrography were satisfactory techniques for diagnosing urethral diverticula and planning appropriate surgical treatment. The urethral pressure profile confirmed the presence of a diverticulum, but noted pressure depressions in cases other than diverticula. Profilometry did not change the surgical plan for treating diverticula, but allowed the planning of additional incontinence surgery in one patient. PMID- 1407898 TI - Should women with familial ovarian cancer undergo prophylactic oophorectomy? AB - OBJECTIVES: To estimate the lifetime probabilities of ovarian cancer in women from families with hereditary ovarian cancer syndromes and those with a family history of ovarian cancer, and to assess the needs for prevention and surveillance in such women. DATA SOURCES: We searched for studies of familial ovarian cancer published since 1966 and used ovarian cancer incidence data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. METHODS: Pooled estimates of relative risk of ovarian cancer among women with a family history of ovarian cancer were derived using statistical methods based on fixed effects. Modified life-table methods were used to estimate the lifetime probability of ovarian cancer. DATA SYNTHESIS: The lifetime probability of ovarian cancer increases from about 1.6% in a 35-year-old woman without a family history of ovarian cancer to about 5% if she has one relative and 7% if she has two relatives with ovarian cancer. The lifetime probability may decrease to about 3-4% if she takes oral contraceptives for 5-9 years. Women from families with hereditary ovarian cancer syndromes may have as high as a 50% lifetime risk of ovarian cancer. CONCLUSIONS: The risk of ovarian cancer in women from families with hereditary ovarian cancer syndromes is sufficiently high to warrant prophylactic oophorectomy. Among women with one relative with ovarian cancer, the lifetime probability of ovarian cancer is not high enough to recommend oophorectomy. However, some women may choose oophorectomy depending on their attitudes concerning risk-taking, surgery, and hormone replacement. Oral contraceptives should be considered as preventive therapy to decrease the risk of ovarian cancer in women with a family history of ovarian cancer. PMID- 1407899 TI - A quantitative assessment of oral contraceptive use and risk of ovarian cancer. AB - OBJECTIVE: To provide a quantitative assessment of the association between oral contraceptive (OC) use and ovarian cancer using results from the published literature. DATA SOURCES: We conducted a MEDLINE literature search for all epidemiologic studies of OC and ovarian cancer published in English between 1970 1991. The reference list for each article was reviewed to locate additional published articles. METHODS OF STUDY SELECTION: We included 20 studies in which a relative risk and either a standard error, confidence interval, or P value was reported, or sufficient data were presented to allow us to calculate these measures. DATA EXTRACTION AND SYNTHESIS: We summarized the findings using weighted averages and regression analyses. We found a summary relative risk of 0.64 (95% confidence interval 0.57-0.73) associated with ever-use of OC, indicating a 36% reduction in ovarian cancer risk. The risk of ovarian cancer decreased with increasing duration of OC use; we noted a 10-12% decrease in risk with 1 year of use and approximately a 50% decrease after 5 years of use. The reduced risk was present among both nulliparous and parous women and it appeared to last for at least 10 years after cessation of use. Although most studies assessed the use of cessation of use. Although most studies assessed the use of OC formulations from the 1960s and 1970s, data from the Cancer and Steroid Hormone Study indicate that the decreased ovarian cancer risk may also be present with current lower-dose formulations. CONCLUSION: The protective effect of OC against ovarian cancer risk should be considered in a woman's decision to use OC. PMID- 1407900 TI - The introduction of nitrous oxide analgesia into obstetrics. AB - Nitrous oxide analgesia was introduced into obstetrics by a young Polish-Russian physician who manufactured the gas himself, mixed it with oxygen, humidified the mixture with water vapor, and devised a mouthpiece for self-administration. After assessing the results on himself, he evaluated the effects on pain relief, maternal emotion, and maternal and fetal heart rates, as well as on the frequency, duration, and strength of uterine contractions in 25 parturients. He recognized that, in contrast to chloroform, nitrous oxide did not alter uterine activity. He concluded that the advantages of nitrous oxide administration far outweighed its disadvantages. PMID- 1407901 TI - Clinicians who provide abortions: the thinning ranks. AB - Access to abortion services in the United States has become increasingly limited because of a decrease in rural hospital providers and a growing shortage of clinicians willing to offer this service. As of 1988, 83% of United States counties had no identified provider. The deficit in numbers of clinicians stems from the current imbalance between incentives and disincentives. The single most powerful incentive appears to be altruism. On the other hand, disincentives include poor pay, frequent harassment, low prestige, suboptimal working conditions, and tedium. In 1990 a symposium on abortion provision was held, sponsored by the National Abortion Federation and ACOG. Among the remedies suggested by the attendees were increasing the integration of abortion training into the mainstream of residency education, improving the pay and work environments for clinicians, and where feasible expanding the capacity of physician providers by using midlevel practitioners working under physician supervision. PMID- 1407902 TI - Half-hitch knot for securing the end of continuous sutures. AB - Exploring means for tying a knot at the end of a continuous suture during laparoscopic surgery, it was found that formation of a single half-hitch over the last loop of the suture can secure the ending of the suture and protect against unraveling. This knot has been used successfully to complete running sutures in various endoscopic, gynecologic, and obstetric procedures. PMID- 1407903 TI - Bowel injury from rollerball ablation of the endometrium. PMID- 1407904 TI - Nafarelin versus leuprolide in ovulation induction for in vitro fertilization: a randomized clinical trial. PMID- 1407905 TI - Post-term pregnancy: fetal death rate with antepartum surveillance. PMID- 1407906 TI - Effects of early postoperative chemotherapy on wound healing. PMID- 1407907 TI - Obstetric care and cesarean birth rates: a program to monitor quality of care. AB - OBJECTIVE: To study the quality of obstetric care in relation to rising cesarean rates, a Task Force was formed in New York state by the Department of Health and ACOG District II. The Task Force also included the Organization of Obstetric, Gynecologic, and Neonatal Nurses and the Hospital Association of New York State. The goals were to enhance hospitals' in-house review processes, standardize terminology, and improve the quality of care. A premise of the program was that if quality of care improved, cesarean rates would fall. METHODS: A Dictionary of Terms was developed to standardize clinical and diagnostic terminology. A two tiered review process was instituted, using internal and external hospital reviews. A format for in-house review of obstetric care was developed and recommended to hospitals. External reviews were conducted at 24 hospitals during 1989-1990. Review teams, composed of obstetrician-gynecologists and obstetric nurses in active obstetric practice, assessed obstetric facilities, staffing, medical care, and the in-house review process. Contacts continued with the hospitals after site visits to follow up on implementation of recommendations. General recommendations to improve care, based on the overall program experience, were distributed to hospitals and physicians as part of educational efforts to improve quality of care. RESULTS: The state cesarean rate reversed. Statistics for 1989 and 1990 showed a stronger downward trend in reviewed hospitals than in non-reviewed hospitals. A survey of reviewed hospitals reported a positive response to the review process. CONCLUSION: A successful quality assurance program can be jointly developed by a state regulatory agency and a medical specialty society. PMID- 1407908 TI - Smoking, pregnancy, and source of prenatal care: results from the Pregnancy Risk Assessment Monitoring System. The Pregnancy Risk Assessment Monitoring System Working Group. AB - OBJECTIVE: To assess the impact of current smoking intervention efforts and to target future efforts by describing the relationships between maternal smoking, smoking cessation, and source of prenatal care. METHODS: We used population-based data from 6319 mothers who delivered live-born infants during 1988 and 1989 in Maine, Michigan, Oklahoma, and West Virginia. The number of women sampled per state ranged from 1490-2659; state-specific response rates ranged from 66-84%. Analysis weights adjusted for selection probability and non-response. RESULTS: The prevalences of maternal smoking before, during, and after pregnancy among women receiving publicly funded prenatal care were 2.3-3.4 times the comparable prevalences among privately insured women receiving prenatal care from private providers. Although many smokers reduced or quit smoking during pregnancy, most resumed or increased their smoking to nearly pre-pregnancy levels by 3-6 months postpartum. CONCLUSIONS: Interventions should target the very high levels of smoking among the 27% of women receiving publicly funded prenatal care. However, from a population perspective, the greatest potential for reduction in smoking is among patients of private providers, who care for 61% of pre-pregnancy smokers. PMID- 1407909 TI - Comparison of questionnaire screening and urine toxicology for detection of pregnancy complicated by substance use. AB - OBJECTIVES: To compare the efficacy of structured questionnaire screening and prenatal urine toxicology for the detection of substance use by pregnant women, and to describe substance use patterns in a group of women presenting to a university-based obstetric clinic. METHODS: All patients presenting to our obstetric clinic for their first prenatal visit were evaluated for evidence of current use of alcohol or any illicit substances. Nursing personnel administered an extensive questionnaire, which included detailed questions about past and current substance use patterns. Urine samples were examined by a commercial laboratory for alcohol and a number of illicit substances. Current users were defined as those who admitted use within the past 30 days or who had positive urine toxicology. RESULTS: Fifty-eight of 302 patients (19.2%) were identified as current users of alcohol or illicit substances. Only 17 of 41 women (41.5%) with toxicologic evidence of recent use admitted to current use. Only 17 of 34 (50.0%) admitting to current use had toxicology positive for any substance. Patients with a history of multiple past substance use were significantly more likely to have positive urine toxicology than those without such a history (26.1 versus 7.4%; P < .005). Among current users, multiple substance use (34.5%) and cigarette smoking (52%) were common. CONCLUSION: A screening combination of structured questionnaire and universal urine toxicology identifies more current users than either technique alone, and neither is clearly superior to the other. A history of multiple substance use may be an important indicator of current use. PMID- 1407910 TI - Recurrence of gestational diabetes mellitus. AB - OBJECTIVE: To assess the influence of several maternal and neonatal variables on the recurrence of gestational diabetes mellitus. METHODS: A retrospective review was conducted on 90 of our patients whose index pregnancy was complicated by gestational diabetes mellitus and whose subsequent pregnancy was also managed at our institution. RESULTS: Forty-seven women (52%) had a recurrence of gestational diabetes mellitus in their subsequent pregnancy. These 47 women had an increased body mass index (BMI) (32.8 +/- 8.2 versus 28.9 +/- 7.2 kg/m2; P < .03) and more large for gestational age (LGA) neonates (38 versus 14%; P < .05) and more of them required insulin during their index pregnancy (38 versus 19%; P < .05) than did those who did not have a recurrence of gestational diabetes mellitus. Women who developed a recurrence of gestational diabetes mellitus also had higher fasting (P < .05), 1-hour, 2-hour, and total glucose tolerance test values (P < or = .01) during their index pregnancy. CONCLUSION: Women with a history of gestational diabetes mellitus who have a BMI greater than 35 kg/m2, whose previous newborn was LGA, and who required insulin during their previous pregnancy are at increased risk for recurrence of gestational diabetes mellitus. PMID- 1407911 TI - Expectant management of preterm ruptured membranes: effects of antimicrobial therapy. AB - OBJECTIVE: To determine whether the addition of broad-spectrum antimicrobial therapy to traditional expectant management improves pregnancy outcome in patients with premature rupture of membranes (PROM) remote from term. METHODS: Patients with preterm PROM before 34 weeks' gestation who were not in labor and had no signs of infection or fetal distress were randomized to one of two study groups: 1) expectant management alone and 2) expectant management plus antimicrobial therapy. Women in the latter group received intravenous ampicillin, gentamicin, and clindamycin for 24 hours, followed by amoxicillin plus clavulanic acid orally for 7 days. Other than antibiotic use, management of the two groups was identical. RESULTS: Significantly more women (P < .01) treated with antibiotics (20 of 48, 42%) remained undelivered 7 days after admission compared with those managed expectantly without antibiotics (seven of 46, 15%). In addition, more neonates in the group managed with antibiotics were admitted to the routine nursery (nine of 48 versus two of 45; P = .03). However, there was no difference between the groups in the frequency of serious maternal or neonatal morbidity. CONCLUSIONS: The addition of broad-spectrum antimicrobial therapy to traditional expectant management of pregnancy complicated by preterm PROM may increase the number of gestations undelivered 7 days after admission. It may also decrease the proportion of infants admitted to special care nurseries. Whether these effects result in significant short- or long-term maternal or neonatal benefit remains to be determined. PMID- 1407912 TI - Approximate entropy, a statistic of regularity, applied to fetal heart rate data before and during labor. AB - OBJECTIVE: To determine whether approximate entropy (ApEn), a new statistic of regularity, when applied to fetal heart rate (FHR) data antepartum or in labor, would offer an advantage over standard statistics of variation in predicting outcome. METHODS: A large data base of antepartum FHR records collected in clinical practice over 10 years was available. Two data sets in labor were stored on disk in small computers interfaced to fetal monitors on-line. Outcomes were assessed using blood gas values on delivery and Apgar scores. RESULTS: Antepartum, when the most favorable form of ApEn was used on 769 good-quality FHR records, the correlation with measurement of short-term variation was high. This was especially true when the fetal pulse interval variation fell below the normal range (less than 6 milliseconds short-term; r = 0.93) and in 20 other records with sinusoidal variation (r = 0.96). Approximate entropy varied with fetal sleep cycles and took longer to calculate than FHR variation. During the last hour of labor, in 319 records, there was no significant correlation between umbilical artery base deficit values on delivery and ApEn measurement. In 871 additional good-quality records of fetuses with normal outcome, the mean (+/- standard error [SE]) ApEn (0.95 +/- 0.005) was significantly greater than in 22 records (0.88 +/ 0.028) from fetuses with abnormal outcome (umbilical artery base deficit more than 12 mmol/L and Apgar score of 3 or less at 1 minute). However, consideration of the frequency distributions of these measurements showed that ApEn did not discriminate between normal and abnormal outcomes. The SD of fetal pulse intervals rose in labor whereas ApEn values fell, confirming that this new statistic of regularity differs from standard statistics of variation. CONCLUSION: Approximate entropy offered no advantage over measurement of short term FHR variation antepartum, and neither measurement predicted outcome in labor. PMID- 1407913 TI - Four-quadrant assessment of amniotic fluid volume: distribution's role in predicting fetal outcome. AB - OBJECTIVE: The amniotic fluid (AF) index has been shown to be a useful tool in the area of antepartum surveillance. An intrapartum AF index less than or equal to 5.0 has been shown to have predictive value with respect to increased perinatal morbidity. This study was designed to determine whether the distribution of the AF within the AF index is related to perinatal outcome. METHODS: Patients presenting for labor and delivery had an AF index determined and were divided into two groups. Patients with greater than 50% of their AF distributed in the upper quadrants were placed in the "upper-greater" group. The remaining patients were placed in the "lower-greater" group. The distribution data were compared with the following variables: meconium staining, 1- or 5 minute Apgar score of less than 7, persistent variable decelerations in the first stage of labor, late decelerations, neonatal intensive care unit admission, cesarean delivery for fetal distress, and umbilical arterial and venous pH less than 7.20. RESULTS: A total of 218 patients were evaluated, 125 in the upper greater group and 93 in the lower-greater group. The upper-greater group had a greater incidence of meconium staining (32.8 versus 9.7%; P < .0001), 1-minute Apgar score of less than 7 (12.0 versus 2.2%; P < .007), variable decelerations (53.6 versus 19.4%; P < .00001), late decelerations (16.0 versus 0%; P < .0001), cesarean delivery for fetal distress (7.2 versus 0%; P < .008), umbilical arterial pH less than 7.20 (29.6 versus 8.9%; P < .0105), and umbilical venous pH less than 7.20 (8.9 versus 0%; P < .0398). These results were maintained regardless of the overall AF index. CONCLUSIONS: The distribution of the fluid within the AF index is predictive of perinatal outcome. In addition, the presence of a high negative predictive value for all of the perinatal indices studied enhances the value of this technique as a potential screening tool. Application of these results could provide additional guidelines in defining the intrapartum management and therapy of patients presenting for labor and delivery. PMID- 1407914 TI - Cord-containing amniotic fluid pocket: a useful measurement in the management of oligohydramnios. AB - OBJECTIVE: To test the hypothesis that among patients with a low amniotic fluid (AF) index, those who have a large cord-containing AF pocket will have a lower risk for adverse perinatal outcome than women with a small cord-containing pocket. METHODS: Gravidas with an antepartum AF index no greater than 5 cm were studied prospectively. The vertical diameter of the single largest cord containing pocket, which was excluded from the calculation of the AF index, was measured. Women with rupture of the membranes, multiple gestation, or fetal anomalies were excluded. RESULTS: Fifty-one women with gestational ages of 35-43 weeks were analyzed. Among 35 who had a cord-containing pocket of no more than 5 cm, eight (23%) had fetal distress necessitating operative delivery and eight neonates had cord arterial pH below 7.20. None of these complications occurred in the 16 women who had a cord-containing pocket above 5 cm (P < .05). The mean AF index (2.9 versus 2.8 cm) was not significantly different between the groups. CONCLUSION: Among women with a low AF index, a cord-containing pocket above 5 cm identifies a subgroup of women at lower perinatal risk compared with those with a smaller cord-containing pocket. The need for intervention may be reduced in women with a cord-containing pocket greater than 5 cm. PMID- 1407915 TI - Sonographically detected hyperechoic fetal bowel: significance and implications for pregnancy management. AB - OBJECTIVE: The clinical significance of sonographically detected hyperechoic fetal bowel has not been fully established. This report describes the natural history, pregnancy outcome, and associated features of 30 cases of prenatally diagnosed hyperechoic fetal bowel. METHODS: Fetal bowel of similar or greater echogenicity than surrounding bone was considered hyperechoic. Fetuses so diagnosed were compared with matched controls and with our general obstetric population to determine the relative frequencies of cystic fibrosis, perinatal death, fetal growth retardation, and fetal trisomies. RESULTS: The incidence of hyperechoic fetal bowel during the study period was 0.2% (30 of 12,776 fetuses). Four of the 30 fetuses (13.3%) with hyperechoic bowel were found to have cystic fibrosis, as compared with one in 2200 (0.05%) in the general population. Hyperechoic fetal bowel was also associated with increased risks for perinatal death (16.7%, versus 3.8% in matched controls and 1.9% in the general obstetric population) and fetal growth retardation (23.3% versus 1.9% and 5%, respectively). One fetus with hyperechoic bowel had trisomy 18, an incidence of cytogenetic abnormalities of 3.3%. This was not significantly greater than observed in our general obstetric population (1.2%) (P > .25). CONCLUSIONS: The sonographic finding of hyperechoic fetal bowel is associated with an increased risk for cystic fibrosis, perinatal death, and growth retardation. The risk of fetal trisomy in cases of isolated hyperechoic bowel appears small. When detected, hyperechoic bowel should prompt a complete and careful fetal anatomical survey, consideration of parental carrier testing for cystic fibrosis, and serial sonographic assessment of fetal growth, with cytogenetic testing reserved for cases demonstrating other structural malformations. PMID- 1407916 TI - Effects of methyldopa on umbilical and placental artery blood flow velocity waveforms. AB - OBJECTIVE: To identify the effects of methyldopa on umbilical and placental artery Doppler velocity waveforms in mild preeclamptic and chronic hypertensive women with blood pressure below 160/110 mmHg. METHODS: Twenty-two normotensive, 11 untreated mild preeclamptic, 14 treated mild preeclamptic, 29 untreated chronic hypertensive, and 14 treated chronic hypertensive women were studied. Methyldopa was begun if the blood pressure remained higher than 140/90 mmHg after 24 hours of hospitalization. The pulsatility index (PI) was measured on days 0 and 7. RESULTS: Blood pressure decreased significantly with methyldopa in chronic hypertensive women only (P < .05). The PI did not vary in the umbilical artery in the five groups, or in the placental artery in normotensive, untreated preeclamptic, and untreated chronic hypertensive women. The PI decreased significantly in treated preeclamptic and chronic hypertensive women (P < .05). Birth weight was similar in the hypertensive groups. CONCLUSION: Methyldopa decreases placental vascular resistance in mild preeclamptic and chronic hypertensive women. PMID- 1407917 TI - Effects of induction of labor with prostaglandin E2 on fetal breathing and body movements: controlled, randomized, double-blind study. AB - OBJECTIVE: To evaluate the effects of prostaglandin (PG) E2, given for induction of labor at term, on fetal breathing and body movements. METHODS: Eighteen women with term pregnancies, mild gestational hypertension, intact membranes, and unripe cervices who were not in labor participated in this study. After a 60 minute baseline ultrasound examination of fetal chest and body movements, recorded on videotape, the patients were randomly assigned to either 3 mg intravaginal PGE2 tablets or controls (placebo intravaginal tablets). Following tablet insertion and a 3-hour observation time, a second 60-minute ultrasound recording of fetal movements was taped. The videotape recordings were interpreted according to the total amount of time occupied by fetal body movements and fetal breathing movements. RESULTS: There was a total of 2180 minutes of ultrasound tape recordings, with 136.2 minutes of fetal body movements (6.2%) and 207.8 minutes of fetal breathing movements (9.5%). Mean (+/- standard deviation) observation times per patient before and after tablet insertion were 60.3 +/- 1.2 and 56.4 +/- 1.2 minutes for the PGE2 group and 60.1 +/- 1.3 and 60.4 +/- 1.1 minutes for the control group. Three hours after PGE2 insertion, there were significant decreases in the percentage of time occupied by body movements (7.8 +/- 3.1 versus 3.4 +/- 2.0%; P < .003) and breathing movements (10.6 +/- 8.6 versus 3.9 +/- 2.3%; P < .007). Three hours after tablet insertion, there were statistically significant decreases in the percentage of time occupied by body movements (P < .025) and breathing movements (P < .01) between the control and study groups. CONCLUSION: Induction of labor with intravaginal PGE2 tablets inhibits fetal body and breathing movements. The effects could be due to direct action on the fetus or indirect effects of PGE2 (through uterine contraction and/or endogenous PG). PMID- 1407918 TI - An assessment of the use of meconium alone as an indication for fetal blood sampling. AB - OBJECTIVE: To assess the validity of meconium as an indication for fetal blood sampling. METHODS: The study design was a prospective observational study in a teaching hospital. Fetal blood samples were taken from 401 women. One hundred sixty-five patients had meconium-stained amniotic fluid (77 of whom had no cardiotocographic abnormalities). In the remaining 236 patients, the indication for fetal blood sampling was cardiotocographic abnormalities without meconium. The main outcome measures were the values of pH and base excess obtained at fetal blood sampling, 1-minute Apgar scores, and umbilical artery pH values. RESULTS: Patients with meconium alone as an indication for fetal blood sampling had higher scalp sample pH values (P < .001) and 1-minute Apgar scores (P < .01) than laboring patients with both meconium and cardiotocographic abnormalities. The patients with meconium alone had higher scalp pH values than patients with cardiotocographic abnormalities but no meconium (P < .001). In only two patients with meconium alone was a fetal scalp pH less than 7.20 (both infants had good Apgar scores at delivery). However, when cardiotocographic abnormalities were present, the finding of meconium was significant, resulting in lower 1-minute Apgar scores (P < .01) despite a lack of difference in fetal blood sample pH values. CONCLUSION: In the absence of cardiotocographic abnormalities, meconium is not an indication for fetal blood sampling. PMID- 1407919 TI - Transvaginal Doppler ultrasound assessment of intratumoral hemodynamic change before and during hypertensive intra-arterial chemotherapy for uterine cancer. AB - OBJECTIVE: To evaluate blood flow in malignant uterine tumors during hypertensive intra-arterial chemotherapy. METHODS: Hypertensive intra-arterial chemotherapy (angiotensin II, cisplatin 100 mg, doxorubicin 40 mg) was given to two women with cervical cancer (stage IVA) and seven with endometrial cancer (three stage IA, one stage IB, two stage II, and one stage III). The intratumoral blood flow velocity waveforms were imaged by transvaginal Doppler ultrasound before and during the chemotherapy in six patients. RESULTS: The mean peak systolic velocity during hypertensive intra-arterial chemotherapy (58.9 +/- 29.3 cm/second) was significantly higher than that before chemotherapy (16.0 +/- 6.3 cm/second) (P < .05). There was a significant difference between the end-diastolic velocity before (5.2 +/- 1.8 cm/second) and during chemotherapy (21.2 +/- 6.8 cm/second) (P < .05). The resistance index value during hypertensive intra-arterial chemotherapy (0.607 +/- 0.094) fell significantly from that before therapy (0.644 +/- 0.119) (P < .05). Blood flow velocity waveforms in normal myometrial tissue could be recorded in three cases; in all, the diastolic flow noted before hypertensive intra-arterial chemotherapy disappeared during chemotherapy. CONCLUSION: These results suggest that hypertensive intra-arterial chemotherapy induces a selective marked increase of blood flow in uterine cancer. PMID- 1407920 TI - Percutaneous nephrostomy and ureteral stenting in gynecologic malignancies. AB - OBJECTIVE: To identify the indications, complications, and efficacy of percutaneous nephrostomies and ureteral stents in women with gynecologic cancer. METHODS: In a retrospective study, 40 women underwent urinary diversion with percutaneous nephrostomy and ureteral stents. Nine had ureteral stenosis on initial presentation, 18 had persistent or recurrent cancer, nine had no evidence of disease, and four had operative ureteral damage. Of the nine who were without disease, seven had a urinary conduit. RESULTS: Thirty-five patients had ureteral stenosis, which was bilateral in 24, and five had a ureteral fistula. Sixteen had a unilateral and 22 had bilateral percutaneous nephrostomies, with two cases having stents only. The most common complication was hematuria. Thirteen women were later hospitalized for pyelonephritis. Twenty-nine (72.5%) had ureteral stents, which were bilateral in 12. Renal function was abnormal in 26, but improved in 14 and returned to normal in six. Five fistulas were managed with ureteral stents alone and four were closed. The median time to death (N = 22) was 5.5 months, 12 months in primary cases versus 5.5 months in recurrent cases. Twelve of the remaining 18 were alive without evidence of disease at a median of 38 months, five were alive with disease at a median of 16 months, and one was lost to follow-up. CONCLUSIONS: These techniques are safe and often improve renal function. The procedures have different roles in women with primary and recurrent gynecologic cancer, in those without evidence of recurrent disease, and in those with urinary conduits. PMID- 1407921 TI - Endometrial metaplasia associated with endometrial carcinoma. AB - OBJECTIVE: To clarify the relationship of metaplasia to endometrial carcinoma. METHODS: Between 1984-1990, 73 cases of stage I-II endometrial carcinoma treated initially by hysterectomy were reviewed histologically. The metaplasias were classified as squamous, syncytial papillary, ciliated-cell, eosinophilic, mucinous, clear-cell, or hobnail. We assessed the histologic type and grade of the carcinoma, depth of myometrial invasion, presence or absence of lymph vascular space invasion, and presence or absence of lymph node metastases. RESULTS: Forty of 73 patients (55%) had one or more areas of metaplasia in the endometrium adjacent to the carcinoma. Ciliated-cell metaplasia (28 of 73; 38%) was the most common type encountered. Women with both endometrial carcinoma and metaplasia were significantly younger than those with carcinoma without metaplasia (P < .05). Compared with carcinomas without metaplasia, those with metaplasia were well differentiated (P < .01) and lacked myometrial invasion (P < .01) and pelvic lymph node metastases (P < .05). The presence of metaplasia was also significantly correlated with the presence of endometrial hyperplasia (P < .01). CONCLUSION: In endometrial carcinomas, the presence of endometrial metaplasia suggests a favorable prognosis. PMID- 1407922 TI - Risk factors for ectopic pregnancy: an Italian case-control study. AB - OBJECTIVE: To analyze risk factors for ectopic pregnancy in a population at low risk for the disease. METHODS: Between September 1989 and February 1991 in Milan, we conducted a case-control study on 120 cases of ectopic pregnancy and 209 controls. The control subjects gave birth at term (more than 37 weeks' gestation) to healthy infants on randomly selected days at the same hospitals where the cases had been identified. RESULTS: The risk of ectopic gestation was about 40% higher in smokers than in controls, and the risk estimates increased with the number of cigarettes smoked per day (chi 2(1) trend 4.21, P = .04) and the duration of smoking (chi 2(1) trend 7.31, P < .01). However, smoking was not associated with the risk of ectopic pregnancy after adjustment for potential confounding factors (including history of pelvic inflammatory disease) in a multivariate analysis (relative risks [RRs] for ten or fewer and more than ten cigarettes per day versus no smoking were 0.8 and 1.1, respectively; chi 2(1) trend 0.10, P = not significant). Infertility problems or difficulty in conception were reported by 32% of the cases and 10% of the controls; the corresponding multivariate RR was 4.7 (95% confidence interval [CI] 2.3-9.5). A history of abdominal surgery was associated with about double the risk of ectopic pregnancy (multivariate RR 2.4, 95% CI 1.4-4.2). Similar estimates were found when the analysis was performed considering various types of surgery separately such as appendectomy, cesarean delivery, and other abdominal surgery. Finally, the risk of ectopic pregnancy was higher in women reporting a history of pelvic inflammatory disease (RR 2.7, 95% CI 0.9-8.7) and increased with the number of sexual partners (chi 2(1) trend 4.51, P = .03). CONCLUSIONS: Problems of infertility or difficulties in conception, history of pelvic inflammatory disease/salpingitis, and abdominal surgery are the main risk factors for ectopic pregnancy in this Italian study. Sexual habits also appear to have some independent effect. PMID- 1407923 TI - Early and late intraventricular hemorrhage: the role of obstetric factors. AB - OBJECTIVE: To evaluate the influence of active phase labor and other obstetric factors on the development of periventricular-intraventricular hemorrhage in the neonate. METHODS: A total of 230 infants were studied. Antenatal enrollment was carried out when estimated fetal weight was 1750 g or less. Serial head ultrasound scans were performed to screen for periventricular-intraventricular hemorrhage, with the initial scan performed within minutes of birth. Scan findings and obstetric and neonatal variables collected prospectively at scheduled intervals were analyzed to determine the significant factors that predispose to intraventricular hemorrhage. RESULTS: In 47 infants (20%), intraventricular hemorrhage was detected within 1 hour of birth (early) and in another 49 (21%) at a later age (late). The overall incidence of hemorrhage was similar between vaginal and cesarean deliveries (41 and 44%, respectively). Early hemorrhage was more frequent in vaginal (28%) than cesarean deliveries (11%), whereas late hemorrhage was more frequent in cesarean deliveries. When the role of delivery mode and labor was analyzed by stepwise logistic regression, the odds ratios for development of early intraventricular hemorrhage increased in the following order: cesarean delivery with no labor, cesarean delivery with latent phase labor, vaginal delivery with forceps use, cesarean delivery with active phase labor, and vaginal delivery without forceps use. For late hemorrhage, the odds ratios increased in the following order: vaginal delivery with forceps, vaginal delivery without forceps, cesarean delivery with no labor, cesarean delivery with latent phase labor, and cesarean delivery with active phase labor. CONCLUSIONS: Active phase labor may predispose to early periventricular intraventricular hemorrhage, but its influence may be attenuated by use of forceps or by abdominal delivery. The protective effect of forceps remains for late periventricular-intraventricular hemorrhage, but abdominal delivery does not seem to protect against late hemorrhage. PMID- 1407924 TI - Prenatal diagnosis of dilated cava septi pellucidi et vergae: associated anomalies, differential diagnosis, and pregnancy outcome. AB - OBJECTIVE: To study the significance of dilated cava septi pellucidi et vergae diagnosed prenatally using ultrasonography. METHODS: Sonographic examinations were performed on 11,200 pregnant women. Transabdominal sonographic examinations were done at 24 weeks or later on 3150 pregnant women and transvaginal sonographic examinations were done between 13-17 weeks on 8050 pregnant women. RESULTS: Eight cases of enlarged cava septi pellucidi et vergae were diagnosed prenatally during the second trimester of pregnancy by transvaginal sonography. In only one fetus did dilatation of cava septi pellucidi et vergae disappear during the third trimester. Associated anomalies, three of which were hydrocephalus, were observed in five fetuses. One fetus had chromosomal translocation 11/22 and one was growth-retarded. Pregnancy was terminated in four cases because of associated fetal anomalies or abnormal chromosomal analysis. One of four neonates died of unexplained metabolic acidosis. One neonate demonstrated cava septi pellucidi et vergae communication with the third ventricle and another had mild hydrocephalus on sonographic examination after birth. The three surviving fetuses had normal development during the first months of life. CONCLUSIONS: When dilated cava septi pellucidi et vergae are diagnosed prenatally, attention should be paid to the possible presence of associated fetal malformations. When a cyst of cava septi pellucidi et vergae is the only abnormal finding observed, termination of pregnancy is not justified. PMID- 1407925 TI - First-trimester exposure to alprazolam. AB - OBJECTIVE: To assess prospectively pregnancy outcome associated with first trimester exposure to alprazolam in order to monitor for early signals of potential drug-related risk to the fetus. METHODS: Reports of first-trimester exposure to alprazolam from patients, physicians, or pharmacists were registered. Information regarding drug exposure, risk factors, and pregnancy outcome was requested at 4.5 and 9 months after registration. RESULTS: From June 1982 through December 1990, 542 pregnancies had been registered. Follow-up data were obtained on 411 registrants. There were 13 live births with congenital anomalies, 263 live births with no congenital anomalies, 47 spontaneous fetal losses, and 88 elective abortions. CONCLUSIONS: No pattern of defects or excess of defects or spontaneous abortions was apparent. Although these findings may provide some reassurance in counseling women following inadvertent prenatal exposure, the cases represent a sample of insufficient size for reaching reliable and definitive conclusions about the safety of alprazolam for pregnant women and their developing fetuses. The cases accumulated in this report represent a sample of insufficient size to confirm or refute previous reports of specific congenital anomalies linked to exposure to benzodiazepines. PMID- 1407926 TI - A prospective comparison of terbutaline and magnesium for tocolysis. AB - OBJECTIVE: To compare the tocolytic efficacy and side effects of parenteral and oral magnesium and terbutaline. METHODS: Ninety-eight patients in labor between 23-35 weeks were prospectively entered into a controlled trial of intravenous and oral magnesium versus subcutaneous and oral terbutaline. Tocolytic effectiveness was judged by delay of delivery for 48 hours or 1 week, and to 37 weeks or more. The need to change therapy to the alternate drug was identified, as were side effects. Entrance characteristics of the population, initial pelvic examination, and concomitant infection or cervicovaginal isolates were noted. Outcomes included gestational age at delivery, birth weights, and Apgar scores. Outcome analysis was based on initial tocolytic therapy. RESULTS: Significantly more patients in the magnesium group delivered at 37 weeks or more: 34 of 46 versus 27 of 52 (P < .05). No significant differences were found for delivery by 48 hours or 1 week. The interval between treatment and delivery was greater for magnesium: 7.1 +/- 3.9 versus 5.0 +/- 3.2 weeks (P < .005). Failure to achieve 37 completed weeks was more often due to obstetric complications than to preterm labor itself. Tocolytic effectiveness was reduced if secondary therapy or re-treatment was required or if the patient had cervical dilatation of 3 cm or greater. Infectious complications were common but were not associated with tocolytic effectiveness. Side effects were more noticeable with oral magnesium and subcutaneous terbutaline. CONCLUSIONS: For short-term tocolysis, no significant difference was found between magnesium and terbutaline. Magnesium was associated with a higher term delivery rate. Idiopathic preterm labor accounted for only a small part of the overall prematurity in the study population. PMID- 1407927 TI - Morning sickness control in early pregnancy by Neiguan point acupressure. AB - OBJECTIVE: To evaluate the antiemetic effect of acupressure at the Neiguan point. METHODS: Sixty women in early pregnancy were entered into a randomized, double blind, cross-over, placebo-controlled trial. During a 12-day period, organized in four steps of 3 days each, the women were divided into two homogeneous groups to test the effectiveness of unilateral and bilateral acupressure. RESULTS: Use of acupressure resulted in a significantly lower frequency of morning sickness compared with placebo treatment. More than a 60% positive effect was found with unilateral and bilateral acupressure, compared with an approximately 30% positive effect of placebo acupressure. Changing from unilateral to bilateral pressure on the Neiguan point caused no significant statistical difference. No noteworthy side effects occurred. CONCLUSION: Acupressure on the Neiguan point relieves morning sickness. PMID- 1407928 TI - Serum lipids, blood pressure, body weight, and serum chemistry in women using subcutaneous contraceptive implants releasing the progestin ST 1435. AB - OBJECTIVE: To study the changes in serum lipids, serum chemistry, blood pressure, and body weight in long-term users of subcutaneous contraceptive implants releasing the progestin ST 1435. METHODS: The study was done in the outpatient clinic of the City Maternity Hospital, Helsinki, Finland. Subdermal implants releasing the progestin ST 1435 were inserted in 30 women for 2 years of use. Healthy women aged 19-35 used the implants for contraception. Measurements of body weight and blood pressure were made and blood samples for lipid analysis (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) and serum chemistry were taken before insertion of the implants and every 6 months thereafter until removal. Results are reported for 30 subjects after 6 months of use, 25 subjects after 12 months, 13 after 18 months, and 12 after 24 months. RESULTS: Blood pressure and serum chemistry, ie, liver enzymes and electrolytes, remained unchanged. Slight weight gain occurred, but was not statistically significant. No statistically significant changes were found in lipids or lipid ratios when comparing the values during use of the implant with the pre-treatment values. CONCLUSIONS: The progestin ST 1435, used parenterally for contraception or progestin therapy, had no adverse effects on serum lipids, blood pressure, or body weight, which are known to be risk factors for coronary artery disease. The steroid had no effects on serum chemistry determinations in long-term use. PMID- 1407929 TI - Sexual assault in postmenopausal women. AB - OBJECTIVE: To examine patient characteristics, patterns of injury, forensic evidence, and the frequency of sexual assault in postmenopausal rape victims from 1986-1991. METHODS: Medical and forensic records were reviewed from 129 postmenopausal women (50 years of age or older) and 129 women from a comparison group (14-49 years of age) who reported having been sexually assaulted. Statistical analysis was performed by Student t test, chi 2, multiple logistic regression, or Fisher exact test. RESULTS: Postmenopausal women represented 2.2% of women reporting sexual assault in Dallas County. The postmenopausal victim was more often white (64%), whereas the younger victim was more often black (53%). Drug or alcohol use within the previous 24 hours was more common in the younger group. Trauma, in general, was common, occurring in 67% of the postmenopausal women and 71% of the younger group (P = not significant). Genital trauma was more common in the postmenopausal group (43 versus 18%; P < .001). Nearly one in three postmenopausal women had genital abrasions or edema. Almost one in five older women had genital lacerations, with one in four severe enough to require surgical repair. In contrast, the frequency of extragenital trauma was more common in younger victims (66 versus 49%; P < .01). Forensic findings were similar in both groups; however, in postmenopausal women motile spermatozoa were seen only in those examined within 6 hours of the assault. CONCLUSION: Postmenopausal women who have been sexually assaulted are more likely to sustain genital trauma than younger victims. PMID- 1407930 TI - The case for confidence intervals. PMID- 1407931 TI - Prenatal programs: what the literature reveals. AB - OBJECTIVES: To review evaluations of prenatal health care programs, examine their methodologic features, and synthesize the findings of high-quality studies. DATA SOURCES: We combined a computerized search of the literature and recommendations of experts to select evaluations published between 1981-1991. METHODS OF STUDY SELECTION: After reviewing the quality of each evaluation in relation to methods and clinical applicability, we selected the highest-quality evaluations and summarized their methods and findings. DATA EXTRACTION AND SYNTHESIS: Trained researchers used a standardized abstraction form for information on main objectives and activities, setting, study design and sample, data collection methods, results, and conclusions. Seven of 22 evaluations met the review criteria. Maternal care coordination and visits by nurses, and specially targeted smoking and nutrition programs, were associated with optimized pregnancy outcomes for certain women, including the poor and very young. Longer participation in prenatal care was an important factor in achieving positive outcomes. Women receiving care from nurse-midwives did not differ in their pregnancy outcomes from women cared for by physicians. CONCLUSIONS: No evaluation met all the review criteria. Selection biases are likely, and thus positive findings may have reflected the types of women who were likely to comply with care rather than the effects of program participation. Many topics were not systematically evaluated. Carefully controlled evaluations of the content, number, and timing of prenatal care visits for women with differing medical and social risks are essential in identifying effective ways to achieve the nation's public health objectives regarding maternal and infant mortality. PMID- 1407932 TI - Hemolytic disease of the fetus: a plea for restraint. AB - The recent addition of fetal blood sampling and transfusion techniques to the management schemes for hemolytic disease of the fetus has expanded clinical options for patient care. Coincident with these techniques is a new aggressiveness toward sensitized pregnancies that, upon review of available data, selects more patients for early and invasive testing than appears necessary. This paper explores the issues of invasive testing and offers guidelines that are more conservative than those recommended in recent reports. PMID- 1407933 TI - Sexual assault: review of a national model protocol for forensic and medical evaluation. New Hampshire Sexual Assault Medical Examination Protocol Project Committee. AB - A national hospital/community model protocol was developed for the forensic and medical examination of victims of sexual assault. This review is designed to assist states in the development of sexual assault protocols. Controversial issues were addressed, including the collection of hair evidence, the importance of semen, mandatory reporting, pregnancy testing and prophylaxis, and sexually transmitted diseases including human immunodeficiency virus. The current role of DNA profiling is reviewed. These issues at the interface of medicine, forensic science, victim advocacy, and the law are analyzed. Representatives of the medical, legal, law enforcement, victim advocacy, and forensic science communities contributed to the development of the protocols at the national and state levels. The importance of a collaborative effort is emphasized. The broad protocol goals are to minimize the physical and psychological trauma to the victim while maximizing the probability of collecting and preserving physical evidence for potential use in the legal system. PMID- 1407934 TI - Laparoscopic myomectomy. AB - Fifty-six patients presenting with infertility (17); bleeding, pain, and pressure symptoms (32); and pelvic mass (seven) associated with leiomyomas were managed with laparoscopic myomectomy. Twenty-four second-look procedures were performed to evaluate healing and adhesion formation. Operative time ranged between 45-443 minutes (mean 157), estimated blood loss varied from 10-400 mL (mean 75), and the mean length of hospital stay was 1 day. Traditional morcellation was used initially but was abandoned because of long operating time; vaginal or abdominal removal (depending on size) proved more satisfactory. Three patients developed subcutaneous emphysema and one had febrile morbidity due to upper respiratory tract infection. There were no other complications. In 24 second-look procedures, adhesions were present in 16 subjects (66%). Twelve of 17 in the infertility group conceived (71%); all 39 patients with other complaints experienced satisfactory relief. There were no reoperations. When myomectomy is indicated, the laparoscopic approach appears to offer an alternative to abdominal surgery in selected patients. PMID- 1407935 TI - Natural oocyte retrieval with intravaginal fertilization: a simplified approach to in vitro fertilization. AB - To simplify in vitro fertilization (IVF), we have combined natural-cycle oocyte retrieval with intravaginal fertilization. Our subjects ranged in age from 28-40 years and were monitored by ultrasound and steroid hormone levels. Oocyte retrieval was carried out under vaginal ultrasound-guided aspiration 32-36 hours after the onset of the LH surge. The oocyte was identified and placed in a sealed capsule containing culture media and sperm. The capsule, in a sealed cryoflex envelope, was placed in the woman's vagina and removed 42-48 hours later. The embryo was then isolated and transferred to the woman's uterus. Fifty-one retrieval cycles were attempted in 45 patients. At least one oocyte was retrieved in 88% of cycles, and fertilization was achieved in 84% of oocytes. Of the five clinical pregnancies (10%), four have delivered and one is ongoing. The cost of this procedure is approximately one-third that of standard IVF. The advantages of our method are the elimination of the use of gonadotropins, the simplicity of monitoring and oocyte retrieval, and the lack of need for expensive laboratory equipment. Natural oocyte retrieval with intravaginal fertilization may prove appropriate for those women requiring IVF who fear multiple pregnancies, have side effects from controlled ovarian hyperstimulation, or cannot afford standard IVF. PMID- 1407936 TI - Mortality and morbidity after intrapartum asphyxia in the preterm fetus. PMID- 1407937 TI - Mortality and morbidity after intrapartum asphyxia in the preterm fetus. PMID- 1407938 TI - Nursing practice issues and answers. What are protocols? What are standing orders? PMID- 1407939 TI - How our present health-care system, by removing patient choice, favors scientists and bureaucrats and discriminates against good physicians. PMID- 1407940 TI - Permanent blindness following retrobulbar hemorrhage after peribulbar anesthesia for cataract surgery. AB - We present a case in which a modified peribulbar anesthesia, administered with a 24-gauge (0.55 x 25 mm) sharp, disposable needle, induced an orbital hemorrhage, resulting in complete and permanent loss of vision. To our knowledge, this is the first report of severe complications following a peribulbar block. PMID- 1407941 TI - An analysis of intraocular lens exchange. AB - We present an analysis of 101 eyes of 98 consecutive patients who underwent intraocular lens (IOL) exchange. The period of follow up ranged from 6 to 71 months (mean, 23 months). Bullous keratopathy was the leading (86.7%) indication for IOL exchange in 45 eyes that had combined penetrating keratoplasty (PKP) and IOL exchange (PKP group). Lens dislocation (36%) and incorrect power (25%) were the most frequent indications for IOL exchange without PKP (56 eyes) (NPKP group). A final visual acuity of 20/40 or better was achieved in 50.5% of the 101 eyes, with 88% having two lines of improvement or remaining within one line of the pre-exchange acuity. The geometric mean visual acuity was significantly improved, from 20/273 preoperatively to 20/125 postoperatively, in the PKP group (P less than .001), and from 20/61 to 20/43 in the NPKP group (P = .001). The main reason for vision less than 20/200 in the 23 eyes in the PKP group was glaucoma (nine eyes) and bullous keratopathy (eight eyes). In the NPKP group, seven eyes (four due to cystoid macular edema, CME) had a visual acuity less than 20/200. Posterior chamber (PC) IOL implantation was associated with significantly better visual acuity than anterior chamber (AC) IOL implantation when performed at IOL exchange (P = .004). The most common complications encountered with IOL exchange were CME (17.8%), hyphema (15.8%), glaucoma (10.9%) and PC opacity (8.9%). PMID- 1407942 TI - Devices for the control of laser transmission across the sclera during transscleral photocoagulation. AB - Improving the reproducibility of transscleral photocoagulation necessitates controlling the transmission of the laser beam through the sclera. Two factors make such control problematic: the locally increased transparency of the sclera resulting from the contact procedure and the occurrence of time-related relaxation phenomena. Two instruments have been devised to help control these factors. The first is a mechanical compensation unit comprised of magnets and a spring that allows the force exerted on the sclera to be adjusted to between 0.1 and 0.4 N, the pressure being determined by the outer diameter of the contact tip. The second instrument monitors the portion of the aiming beam reflected by the sclera as a means of determining the exact level of power actually transmitted through it. This information theoretically could be fed back to the treatment laser, allowing the level of power being delivered to be adjusted accordingly. PMID- 1407943 TI - A new instrument for controlling pressure exerted on the sclera during contact Nd:YAG laser cyclodestruction. AB - We tested the device described by Rol et al in their article in this issue, designed to define and precisely control the pressure applied to the sclera during contact cyclodestruction with a cw-Nd:YAG laser. Since scleral transparency, and hence transmission of laser energy, depends on the pressure applied, control of this parameter represents an important advance toward the goal of standardizing the cyclodestructive procedure. In eight of nine cadaver pig eyes, pressure was exerted on the sclera using the pressure-controlling device, with a setting of 0.25 N for two of these eyes, and one of 0.4 N for the other six. In the remaining eye, pressure was controlled intuitively by an experienced surgeon. Applying forces of 0.25 or 0.4 N yielded similar success rates, although these fluctuated greatly even under constant pressure conditions (from 17% to 50% at 0.25 N; from 27% to 42% at 0.4 N). The highest success rate (55%) was achieved by the intuitively controlled pressure irradiations of the experienced surgeon. The variation in coagulation intensity that occurred despite constant pressure suggests that additional factors contribute to the results achieved. Nonetheless, this pressure-controlling probe represents an important achievement. It will permit not only the novice but even experienced operators to adhere unambiguously to a protocol of quantitative, reproducible parameters, and will also help researchers to better understand the relationship between energy delivered and intraocular pressure reduction achieved in contact cyclophotocoagulation. PMID- 1407944 TI - Racial variation of optic disc parameters in children. AB - The optic disc parameters of 66 children without ocular disease were analyzed in a prospective study. The vertical disc diameter, the disc area, and the cup-to disc ratio were significantly larger in blacks than in whites. The race-based variation of optic disc size demonstrated previously in adults appears to be inherited, as it is also present in children. PMID- 1407945 TI - Extrusion of enucleation implants: treatment with secondary implants and autogenous temporalis fascia or fascia lata patch grafts. AB - We performed one autogenous fascia lata graft and 11 autogenous temporalis fascia grafts in eight patients with extrusion of an orbital enucleation implant and in four patients with a bulging implant who could not wear a prosthesis. Excluding one patient with inadequate follow up, 10 of the 11 patients (91%) successfully retained their implant. One patient had severe conjunctivitis followed by anterior migration of his implant 2 1/2 years after patch grafting, necessitating replacement of the implant. We conclude that autogenous temporalis fascia patch grafting is an effective treatment for orbital enucleation implant extrusion or a bulging implant. PMID- 1407946 TI - Forming and teaching true knots for strabismus surgery. AB - I describe a system for ensuring the formation of true knots in the locking bites in strabismus surgery. I also present a method for teaching this system to residents that makes use of a piece of cotton or nylon rope, a cotton mop refill, and the end of a garden rake. PMID- 1407947 TI - Office probing of congenital nasolacrimal duct obstruction. AB - We report the results of office nasolacrimal duct probing under topical anesthesia in 2369 eyes with symptomatic nasolacrimal duct obstruction. The overall success rate for cure by initial probing was 92%. In patients less than 9 months old, a 94% cure rate was achieved with one probing; in patients 9 months and older, the rate decreased to 84%. The decrease in success rate after 9 months was statistically significant (P less than .00001 by chi-square analysis). A majority of 180 parents of these patients surveyed said they were happy with the office procedure and preferred having the probing performed to resolve symptoms, even though they realized that the symptoms most probably would resolve by 1 year of age without it. We conclude that office probing for congenital nasolacrimal duct obstruction is a safe and effective method for treatment of symptomatic nasolacrimal duct obstruction, allowing the cost and risk of general anesthesia as well as the cost and inconvenience of prolonged medical management to be avoided. PMID- 1407948 TI - Canaliculocystostomy combining microsurgery and fibrin sealing of the anastomosis. AB - I present a method of using fibrin sealing for anastomosis in canaliculocystostomy. A microsurgical resection of the stenosis of the common canaliculus is followed by silicone intubation of the lacrimal apparatus and fibrin sealing of the anastomosis of the canaliculi and the lacrimal sac. The silicone tube is removed 6 months postoperatively. This technique obviates microscopic sutures, reduces operating time, and provides hemostasis. Of seven patients with monolateral stenosis of the common canaliculus in whom this technique was used and who were followed for a minimum of 3 years, only one had a restenosis. PMID- 1407949 TI - Monopolar cautery for graft cartilage sculpting in reconstructive eyelid surgery. AB - We describe a technique for using the monopolar cautery to sculpt ear cartilage to prepare it for use as a graft to reconstruct or support the posterior lamella of the eyelid in oculoplastic procedures. We have used this simple, rapid, and predictable technique in 16 patients with excellent results. PMID- 1407950 TI - Microblepharon. AB - We describe a child with microblepharon and corneal exposure secondary to lagophthalmos. Surgical reconstruction utilizing full-thickness skin grafts to all four lids corrected the lagophthalmos and relieved her symptoms. PMID- 1407951 TI - A modified technique of transscleral suture fixation of posterior chamber lenses. AB - I describe a modified technique of sulcus fixation of posterior chamber intraocular lenses (PC-IOLs) in which the anterior vitrectomy is restricted to the vitreous base and anterior chamber and a single-armed sling suture is used. These modifications reduce operating time and the risk of intraoperative and postoperative infection. This technique has been used successfully in the last 20 of the 96 patients in our institution who have had transscleral suture fixation procedures. PMID- 1407952 TI - Peribulbar anesthesia in retinal reattachment surgery. AB - We prospectively evaluated the effectiveness of peribulbar anesthesia in retinal reattachment surgery. Of the 24 patients studied, 2 required retrobulbar supplementation during the latter part of the surgery. Our results show that peribulbar anesthesia can be effectively used for retinal reattachment surgery and probably should be the preferred form of local anesthesia for this surgery, since the eyes involved have a relatively high incidence of axial myopia and posterior staphyloma. PMID- 1407953 TI - Sub-Tenon's anesthesia for trabeculectomy. AB - Sub-Tenon's anesthesia for anterior segment surgery avoids the risks associated with retrobulbar and peribulbar injections. Localized injections over the appropriate rectus muscles ensure patient comfort as well as optimal exposure of the surgical field in eyes undergoing trabeculectomy. We have used this technique without significant complications in approximately 400 procedures. PMID- 1407954 TI - Effect of vitamin E in the treatment of bovine-albumin-induced uveitis in rabbits. AB - In order to assess the role of vitamin E, an antioxidant, in the treatment of uveitis, a controlled experimental study was carried out on 20 New Zealand albino rabbits with bovine-albumin-induced uveitis. In all vitamin-E-treated animals, clinical and histopathological study of the retina and uvea revealed no significant changes in comparison with those in untreated rabbits. PMID- 1407955 TI - Similarities and differences between the Kelman phacoemulsification and extracapsular cataract extraction procedures in the spontaneous regression of corneal astigmatism from against-the-rule astigmatism. AB - We perspectively examined the induction and spontaneous regression of corneal astigmatism from preoperative against-the-rule astigmatism [Kelman phacoemulsification (KPE), n = 618; extracapsular cataract extraction (ECCE), n = 192] among cataract extraction surgeries (KPE, n = 1,648; ECCE, n = 443). All data were set on a double-angle coordinate graph, from which the mean +/- SE of the axis and the amount of astigmatism were obtained simultaneously. In the KPE group, the surgically induced astigmatism was independent of preoperative state or age. In the ECCE group, surgically induced astigmatism shifted toward with-the rule astigmatism, and postoperative recovery was delayed longer in patients over 80 years of age than in those under 70. Postoperative against-the-rule astigmatism was more frequent after KPE. Our first trial to calculate astigmatism from a double-angle coordinate graph was useful in showing astigmatism changes. PMID- 1407956 TI - Intraocular kinetics of ceftazidime (Modacin). AB - The concentration of ceftazidime was determined in the aqueous humor and the vitreous body of normal, vitrectomized and aphakic/vitrectomized eyes and in the serum of albino rabbits 1 h after intravenous injection of 100 mg/kg ceftazidime. The intravitreal ceftazidime concentration was low (0.1-0.2 microgram/ml) in normal eyes 1 h after intravenous injection, and high (8.7 +/- 8.5 micrograms/ml) in vitrectomized and aphakic/vitrectomized eyes when injected immediately after surgery. The ceftazidime concentration was also determined in the aqueous humor and the vitreous body of normal eyes and in the serum of albino rabbits 3, 6, 12, 24 and 48 h after intravitreal injection of 200 micrograms. The intravitreal ceftazidime concentration after intravitreal injection decreased exponentially for 12 h (half-life about 7.4 h). It decreased more slowly thereafter and remained at 13.0 micrograms/ml (mean) even 48 h after injection. This concentration exceeded the minimum inhibitory concentrations against common gram positive and gram-negative organisms causing endophthalmitis. PMID- 1407957 TI - Spindleform scleropathy: collagen changes of the sclera. A pathologic report. AB - To our knowledge, this is the first pathologic report of interscleral collagen bundle changes occurring as well-defined spindleform lesions randomly interspersed within the sclera. The lesions were observed in an otherwise healthy 75-year-old man whose eye was enucleated because of a uveal malignant melanoma. There are few reports in the literature of focal scleral changes of a predominantly acid mucopolysaccharide nature. The entity we observed in this case differs from these reports by its spindleform appearance, random distribution (not overlying the melanoma) and predominantly vicinal glycol nature. Histopathologic, histochemical, and ultrastructural studies revealed that the lesions were not the result of mucoid degeneration of the scleral collagen and not an abnormal collagen structure. PMID- 1407958 TI - Retino-choroidal changes in endotoxin-induced uveitis in the rat. AB - A single injection of 100 micrograms of lipopolysaccharide from Salmonella typhimurium in the foot pads of Lewis rats induced acute inflammation of the eye. Clinically, the disease started as early as 0.5 h and peaked 18 h after the inoculation. The aqueous protein concentration was increased after the inoculation. Histopathologically, cellular infiltrates and proteinaceous exudates were observed in the anterior segment (anterior chamber, iris and ciliary body). In addition to those changes described in previous reports, the examination of the posterior segment showed retinal vasculitis, hemorrhagic exudates, focal destruction of photoreceptor cells and choroidal infiltration. PMID- 1407959 TI - Argon laser photocoagulation of the pecten oculi of the domestic pigeon (Columba livia) using a specially designed contact lens. AB - A specially designed -62-D polymethylmethacrylate contact lens for biomicroscopy of the fundus oculi of the pigeon is presented. The study shows the usefulness of the lens in argon laser photocoagulation of the pecten, a noninvasive technique for ablating the organ. In addition, previous studies on operative destruction of the pecten are reviewed. To our knowledge, this is the first time the macroscopic appearance of a photocoagulated pecten is documented. PMID- 1407961 TI - Quantification of angiogenesis due to basic fibroblast growth factor in a modified rabbit corneal model. AB - The rabbit corneal angiogenesis assay was modified to allow quantification of the neovascular response induced by growth factors. Basic Fibroblast Growth Factor (bFGF) was used for this experiment. bFGF was diluted in phosphate buffer solution (PBS) in such a way that 2 microliter of solution contained concentrations ranging from 17 to 1,200 ng. Each drop was absorbed by a 1 x 2 mm particle of a dried 70% hydratable hydrogel and implanted into a mid-stroma corneal pocket, 2 mm from the limbus. Iodinated bFGF was used to measure growth factor diffusion in the cornea, which was found to be isotropic. Autoradiography showed that bFGF was stored in the cornea at both epithelial and endothelial level. Corneal neovascularization occurred on the second day after implantation and was maximal on the 7th day. At this time the neovascular surface was measured by planimetry on corneal photographs and compared with controls. This method allows precise definition of the dose of any substance to be implanted into the cornea and induces a rapid neovascular response, thus allowing quantitative evaluation of neovascularization within one week. A neovascular response was detectable for doses as low as 35 ng of bFGF and increased proportionally to the dose of bFGF implanted. PMID- 1407960 TI - Aqueous humor polyamines and alkaline phosphatase activity in endotoxin-induced uveitis: correlations to diverse leukocyte subsets. AB - The polyamines putrescine, spermidine and spermine have been proposed to be a part of the acute phase inflammatory response. They have been shown to be useful markers for cellular kinetics and change with various pathological conditions. The hypothesis that aqueous humor polyamines could be used to follow the time course of an endotoxin-induced inflammation in the eye was investigated. Additional parameters studied were the amount of aqueous leukocytes, alkaline phosphatase activity, distribution of leukocyte subsets and breakdown of the blood-aqueous barrier. Aqueous leukocytes, protein, alkaline phosphatase activity, putrescine and acetylated spermidine increased significantly as a response to inflammation during the first days after uveitis induction. Spermidine decreased 24 h after injection and seemed to rise thereafter. The different polyamines, except spermidine, correlated to the diverse infiltrating leukocyte subsets. These observations indicate that aqueous polyamines may be applied as valid markers for inflammation in the eye. PMID- 1407962 TI - Retained nuclei after cataract surgery. PMID- 1407963 TI - Retained nuclei after cataract surgery. PMID- 1407964 TI - Pseudotumor cerebri from venous obstruction. PMID- 1407965 TI - Swab culture of corneal ulcers. PMID- 1407966 TI - Managing dislocated IOLs. PMID- 1407967 TI - The timing of retinal detachment surgery: patient and physician considerations. PMID- 1407968 TI - Pars plana vitrectomy in the Early Treatment Diabetic Retinopathy Study. ETDRS report number 17. The Early Treatment Diabetic Retinopathy Study Research Group. AB - BACKGROUND: The Early Treatment Diabetic Retinopathy Study (ETDRS) enrolled 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy in both eyes. Patients were randomly assigned to aspirin 650 mg/day or placebo. One eye of each patient was assigned randomly to early photocoagulation and the other to deferral of photocoagulation. Follow-up examinations were scheduled at least every 4 months, and photocoagulation was initiated in eyes assigned to deferral as soon as high-risk proliferative retinopathy was detected. Aspirin was not found to have an effect on retinopathy progression or rates of vitreous hemorrhage. The risk of a combined end point, severe visual loss or vitrectomy, was low in eyes assigned to deferral (6% at 5 years) and was reduced by early photocoagulation (4% at 5 years). Vitrectomy was carried out in 208 patients during the 9 years of the study. This report presents baseline and previtrectomy characteristics and visual outcome in these patients. METHODS: Information collected at baseline and during follow-up as part of the ETDRS protocol was supplemented by review of clinic charts for visual acuity and ocular status immediately before vitrectomy. RESULTS: Vitrectomy was performed in 208 (5.6%) of the 3711 patients (243 eyes) enrolled in the ETDRS. The 5-year vitrectomy rates for eyes grouped by their initial photocoagulation assignment were as follows: 2.1% in the early full scatter photocoagulation group, 2.5% in the early mild scatter group, and 4.0% in the deferral group. The 5-year rates of vitrectomy (in one or both eyes) were 5.4% in patients assigned to aspirin and 5.2% in patients assigned to a placebo. The indications for vitrectomy were either vitreous hemorrhage (53.9%) or retinal detachment with or without vitreous hemorrhage (46.1%). Before vitrectomy, visual acuity was 5/200 or worse in 66.7% of eyes and better than 20/100 in 6.2%. One year after vitrectomy, the visual acuity was 20/100 or better in 47.6% of eyes, including 24.0% with visual acuity of 20/40 or better. CONCLUSIONS: With frequent follow-up examinations and timely scatter (panretinal) photocoagulation, the 5-year cumulative rate of pars plana vitrectomy in ETDRS patients was 5.3%. Aspirin use did not influence the rate of vitrectomy. PMID- 1407969 TI - Outcome and cost analysis of scheduled versus emergency scleral buckling surgery. AB - BACKGROUND: Retinal detachments are usually considered to be a surgical emergency. However, there are additional risks and costs for unnecessary emergency surgeries. The purpose of this study is to evaluate whether the conventional wisdom for treating all retinal detachments as emergencies needs to be re-examined. METHODS: Forty-eight patients who had an emergency scleral buckle and 89 patients who had a scheduled procedure were randomly selected from 884 consecutive patients who had a primary scleral buckling procedure during a 4 1/2 year period. The medical records of each patient were used to obtain detailed information related to prognosis. The visual acuity measurements of each patient, taken 6 months after the procedure, were obtained from the records of the ophthalmologist following the patient. Linear regression analysis was used to compare the final visual outcome for patients who had emergency surgery with patients who had scheduled surgery after taking into account patient factors related to prognosis. RESULTS: Patients selected for emergency surgery had better visual prognoses than scheduled patients but had the same risk of systemic complications and the same extent of detachment if the macula was not involved. None of the 18 patients with an attached macula experienced macular involvement while awaiting scheduled surgery. There were no differences between emergency and scheduled patients in ocular or systemic complications, rate of reattachment, rate of decreased visual acuity after surgery, visual outcome adjusted for prognosis, or, since 1985, length of hospital stay. A greater cost was incurred for the patients having emergency surgery due to difference in pay scales for support personnel. CONCLUSIONS: Because the study is not large and the patients were not randomized to treatment, the results are not definitive. However, they suggest that emergency surgery is unnecessary for many patients with a detached retina. PMID- 1407970 TI - Proliferative vitreoretinopathy. Lymphocytes in epiretinal membranes. AB - BACKGROUND: To investigate the potential contribution of inflammatory and immune mediated processes contributing to the pathogenesis of proliferative vitreoretinopathy (PVR), an immunohistochemical study was undertaken to characterize the infiltrating inflammatory cells in epiretinal membranes surgically removed from the eyes of patients with PVR. METHODS: Twenty-one epiretinal membranes obtained surgically from eyes with PVR complicating rhegmatogenous retinal detachment were studied immunohistochemically using the ABC technique and a panel of monoclonal and polyclonal antibodies. RESULTS: T lymphocytes were found in 18 of the 21 specimens and generally constituted a small percentage of the total cell number. CD4+ T cells were found in 14 of the 18 membranes containing T cells. Three of six frozen membranes contained T cells that were positive for the interleukin-2 receptor. In 5 of 16 membranes studied, cells positive for the macrophage/monocyte marker were found. No B lymphocytes or neutrophils were identified, and there were no deposits of complement or immunoglobulins. Positive staining for the class II MHC antigen HLA-DR was found in 7 of the 21 membranes, a result that was more consistent in frozen than in fixed tissues. CONCLUSION: The study suggests that T lymphocytes are present in PVR epiretinal membranes and may be activated. These cells have the potential to play a role in the pathobiology of PVR. PMID- 1407971 TI - Ultrastructural immunocytochemistry of subretinal neovascular membranes in age related macular degeneration. AB - BACKGROUND: The authors studied various cellular and extracellular matrix components of subretinal neovascular membranes (SRNVM) from patients with age related macular degeneration (ARMD). METHODS: Electron microscopic immunocytochemistry was used on the subfoveal neovascular membranes surgically removed from three patients with disciform lesions due to ARMD. FINDINGS: The SRNVMs always contained large "feeder" vessels along with many new capillaries in different stages of maturation. Capillaries were sparse and embedded in an abundant stroma. The majority of the nonvascular cells were either retinal pigment epithelial (RPE) cells or fibroblast-like cells. The RPE cells formed single or multiple layers on one side of the membranes. The stroma was composed mainly of collagen types I and IV and fibronectin, with small amounts of collagen types III, V, and VI. The absence of Bruch's membrane suggests that a splitting may occur between the RPE cells and Bruch's membrane with the new vessels growing into this cleft. A thickened layer of collagen type IV was often present under the RPE cells. The basement membranes of the newly formed capillaries were morphologically ill-defined, and contained substantial amounts of collagen type IV and fibronectin, but, unlike the basement membranes of normal capillaries, they lacked laminin or heparan sulfate proteoglycan. CONCLUSION: These results on the ultrastructural components of the SRNVMs may be useful in clarifying the nature of the disciform process in ARMD. PMID- 1407972 TI - Dominantly inherited cystoid macular edema. A histopathologic study. AB - BACKGROUND: Dominantly inherited cystoid macular edema was described as a clinically distinct form of macular dystrophy with an onset at approximately age 30 years with slow progression over the ensuing decades. This is the first report of the light and electron microscopic findings in two donor eyes of one of the patients with this clinical entity. METHODS: Both eyes were obtained after death and fixed within 24 hours in a buffered 4% formaldehyde-1% glutaraldehyde solution. For light microscopy, tissue was embedded in paraffin and stained with hematoxylin-eosin, periodic acid-Schiff, colloidal iron for mucopolysaccharides, and an antibody to glial fibrillar acidic protein. For ultrastructural investigation, several blocks of choroidal/retinal tissues from the posterior pole, including both maculae, were embedded in epoxy resin and processed for transmission electron microscopy. RESULTS: Major findings included large retinal cysts in the macula, atrophy and marked disorganization of the inner nuclear layer, advanced degeneration of Muller cells with nodular aggregates of basement membrane-like material, and a preretinal membrane. The retinal vasculature did not show excessive endothelial alterations but was surrounded by deposits of multilayered basement membrane in the perivascular space. CONCLUSION: The authors believe that the pathologic features of dominantly inherited cystoid macular edema are different from those of macular edema caused by other disease processes. The predominant pathologic changes affected mainly the inner nuclear layer. The possibility of a primary disease of the Muller cell is suggested. PMID- 1407973 TI - Low-dose methotrexate therapy for ocular inflammatory disease. AB - BACKGROUND: Methotrexate is a second-line anti-inflammatory agent used in the treatment of rheumatic diseases. At low doses (12.5 mg/week), it is associated with few serious side effects. METHODS: Twenty-two patients (5 men, 17 women) with chronic noninfectious ocular inflammatory disease, who had not responded to or who had become intolerant of corticosteroid or alternate cytotoxic agents, were treated weekly with oral low-dose, pulse methotrexate. Treated diseases included chronic uveitis-vitreitis (9), scleritis (4), inflammatory pseudotumor (3), orbital myositis (3), and retinal vasculitis (3). RESULTS: Follow-up ranged from 2 to 39 months (mean, 11 months). Response time ranged from 3 to 9 weeks (mean, 5 weeks) after implementation of methotrexate therapy. Sixteen of 22 patients had reduction of inflammatory activity. Fourteen of these 16 patients were able to taper or discontinue corticosteroid therapy. Five patients had complete remission of their disease; six patients did not respond to methotrexate. CONCLUSION: Treatment with low-dose methotrexate appears to be effective therapy for steroid-resistant ocular inflammatory disease. PMID- 1407974 TI - Ocular findings associated with neurofibromatosis type II. AB - BACKGROUND: Neurofibromatosis has been recently acknowledged as consisting of a number of different diseases. Neurofibromatosis (NF) type I and NF type II are the most clearly defined. Type II is characterized by bilateral acoustic neuromas and is rare (its incidence is 1/50,000). The previously reported ocular associations of NF type II are posterior subcapsular cataracts, Lisch nodules, and combined hamartomata of the retinal pigment epithelium and retina. In this study, the authors attempt to define further the ocular manifestations of NF type II. METHODS: The authors prospectively examined 9 patients who met the diagnostic criteria for NF type II (age, 18 to 38 years; mean, 25 years). RESULTS: Seven of nine patients had epiretinal membranes in the posterior pole. None of these epiretinal membranes were visually significant. In addition, five patients had central posterior cortical cataracts and five had peripheral wedge-shaped cortical cataracts. CONCLUSION: The presence of epiretinal membranes in young patients may represent another clinical finding associated with NF type II. Epiretinal membranes, central posterior cataracts, peripheral cortical cataracts, or combined hamartoma of the retinal epithelium and retina in young patients should alert the ophthalmologist to include NF type II in the differential diagnosis in patients with stigmata of NF type II. PMID- 1407975 TI - Atypical presentation of fungal dacryocystitis. A report of two cases. AB - BACKGROUND: Candida albicans has only rarely been implicated in nasolacrimal duct obstruction. Its association with dacryoliths is well known, but it is unclear whether it is an etiologic factor or is present as a result of the obstruction. FINDINGS: The authors report 2 cases of fungal dacryocystitis that were not associated with dacryolith formation and where Candida species appear to be the primary etiologic agent. CONCLUSION: The possibility of a fungal infection should be considered in the evaluation of "routine" chronic dacryocystitis, particularly in the presence of corneal ulceration or postoperative endophthalmitis, as prompt initiation of appropriate therapy may be crucial. PMID- 1407976 TI - Miniplate reconstruction of the lateral orbital rim after orbital decompression for Graves disease. AB - BACKGROUND: Removal of lateral orbital bone with or without simultaneous removal of the lateral orbital rim is an accepted method of orbital decompression for Graves disease. Once removed, the bone is no longer available for reconstruction and secondary complications such as rounding of the canthal angle, canthal dystopia, and globe dystopia may result. METHODS: The authors replaced the excised bone with a titanium miniplate to protect the globe and fixate the lateral canthal tendon in 18 patients (33 orbits). The orbital rim and lateral orbital wall were completely removed, and the inner aspect of the orbit was enlarged with a cutting burr. A standard titanium miniplate was then anchored to remaining bone, and soft tissue was secured to the miniplate to reconstruct the lateral canthus. RESULTS: The results, as manifest by appearance of the lateral canthus and position of the eyelid in apposition to the globe, were graded as excellent in all patients and orbits. There were no early or late complications. CONCLUSION: Miniplate reconstruction of the lateral orbital rim after decompression for Graves disease allows the beneficial affect of lateral decompression and preserves the functional aspect of the lateral orbital wall. PMID- 1407977 TI - Multidisciplinary approaches to complicated vascular lesions of the orbit. AB - BACKGROUND: Hemodynamically active vascular lesions of the orbit are often clinically challenging to treat, both because of the complexity of the vascular anatomy and the delicacy of the cardinal structures that are involved and vulnerable to damage. Attempts to achieve complete embolization of such vascular lesions may result in damage to vital visual structures. Conversely, incomplete closure of the feeders or vascular shunts will usually result in recanalization and, therefore, recurrence of such lesions. METHODS: Surgical excision after selective optimal embolizations may convert dynamic lesions into static ones with controlled surgical risks and could provide a solution to these problems. Cyanoacrylic polymerization was used to embolize the lesions, which were then excised with careful microsurgical and microvascular techniques. RESULTS: The authors present four cases of different hemodynamically active orbital vascular lesions (a post-traumatic arteriovenous fistula, a complex venous anomaly, a cavernous hemangioma of bone, and an arteriovenous malformation), which were treated successfully with the combination of presurgical embolization and surgery. CONCLUSION: The authors believe that, from their experience with these cases, a multidisciplinary approach to complicated orbital vascular lesions is ideal and practical. PMID- 1407978 TI - Microanatomy of the orbital apex. Computed tomography and microcryoplaning of soft and hard tissue. AB - PURPOSE: The anatomy of the orbital apex is characterized by a complex interplay between critical bony and neural structures. Traditional methods used to study this region include dissection, static sections, and computed tomography (CT). Tomographic techniques are very useful in understanding these complex relationships, but the resolution of conventional CT and magnetic resonance imaging (MRI) is not sufficient to recognize the intricate details of the optic nerve canal and associated structures. The purpose of this study is to determine the value of microcryoplaning and computer reconstruction in visualizing the orbital apex in detail not previously possible, at any orientation in three dimensional space. METHODS: Microcryotomy of the orbital apex area was performed on cadaver specimens, and images of each cryosection were digitized. Subsequently, the lesser wing of sphenoid bone and optic nerve were outlined to allow for spatial manipulation and three-dimensional visualization of the orbital apex. RESULTS: The authors present reconstructed computer images of the orbital apex in coronal and axial planes with CT correlation. Clinically important anatomic points and landmarks as well as potential pitfalls are demonstrated. CONCLUSION: Microcryoplaning and computer reconstruction are useful techniques in viewing the detailed anatomy of the orbital apex. Although microcryoplaning has the limitation of poor soft tissue detail, the resolution of captured images is much greater than those obtained from CT or MRI scans; the improved resolution allows for accurate CT correlations. The technique has utility in education, surgical planning, and quantitative analysis of orbital apical anatomy. PMID- 1407979 TI - Color Doppler imaging of the ocular ischemic syndrome. AB - PURPOSE: This study describes hemodynamic characteristics of the ophthalmic, central retinal, and posterior ciliary arteries in 16 eyes of 11 patients with the ocular ischemic syndrome. Understanding the hemodynamic characteristics of the retrobulbar circulation may elucidate the natural history and pathophysiology of the ocular ischemic syndrome and perhaps form the basis for rational treatment of this condition. METHODS: Color Doppler imaging, a procedure that permits rapid noninvasive imaging of the ophthalmic, central retinal, and posterior ciliary arteries, was used to quantitate peak systolic blood flow velocities and vascular resistance (pulsatility index) within these vessels in study group eyes and in an age-matched control population. RESULTS: We demonstrated markedly reduced ocular ischemic syndrome central retinal and posterior ciliary artery peak systolic velocities compared with control group eyes. Central retinal and posterior ciliary artery vascular resistance (pulsatility index) was greater in ocular ischemic eyes versus control group eyes. Reversal of ophthalmic artery blood flow was detected in 12 of 16 ocular ischemic syndrome eyes. Study group eyes with poor vision had no detectable posterior ciliary arterial blood flow. CONCLUSION: Color Doppler imaging quantitates hemodynamic characteristics of the retrobulbar circulation in the ocular ischemic syndrome. There is markedly reduced peak systolic velocity and increased vascular resistance in ocular end arteries such as the central retinal and posterior ciliary arteries. Ophthalmic artery reversal of flow seems to represent collateral blood flow to lower resistance vascular beds. Posterior ciliary artery hypoperfusion may correlate with poor vision in the ocular ischemic syndrome. PMID- 1407980 TI - Acute promyelocytic infiltration of the optic nerve treated by oral trans retinoic acid. AB - BACKGROUND: Oral trans-retinoic acid has recently been shown to be an effective treatment modality for acute promyelocytic leukemia. This type of drug differs from traditional tumoricidal agents by promoting differentiation of the malignant, immature cells. METHODS: The authors describe a patient with optic nerve infiltration by acute promyelocytic leukemia documented ophthalmoscopically and confirmed by standardized echography and magnetic resonance imaging. High resolution chromosome banding revealed the patient had a 15;17 chromosomal translocation known to be associated with acute promyelocytic leukemia. Treatment was instituted with oral all trans-retinoic acid without adjuvant radiotherapy or intrathecal chemotherapy. RESULTS: Results of serial bone marrow examination showed progressive differentiation of malignant cells with complete bone marrow remission. Results of serial ophthalmic examinations showed complete resolution of the leukemic optic nerve head infiltration. CONCLUSION: All trans-retinoic acid alone can be an effective treatment for optic nerve head infiltration in acute promyelocytic leukemia. This case suggests that radiation therapy may not be necessary in acute promyelocytic leukemia with optic nerve infiltration. PMID- 1407982 TI - Effect of brief exposure to mitomycin C on viability and proliferation of cultured human Tenon's capsule fibroblasts. AB - PURPOSE: The purpose of this study is to determine why a single intraoperative dose of mitomycin C (MMC) appears to promote the success of glaucoma filtration surgery. METHODS: Human Tenon's capsule fibroblasts were exposed to MMC and 5 fluorouracil (5-FU) in vitro at the concentrations and durations of exposure used clinically. Cell proliferation was assessed by quantification of 3H-thymidine uptake. Cell viability was studied using a sulfarhodamine B cell protein stain and by trypan blue exclusion. RESULTS: Neither MMC (0.4 mg/ml) nor 5-FU (40 mg/ml) were cytocidal. Both 1- and 5-minute exposures to MMC were antiproliferative. A 1-minute exposure to 0.4 mg/ml inhibited 3H-thymidine uptake by 77%. For the 5-minute exposure, 3H-thymidine uptake was inhibited by 50% at 0.06 mg/ml and by 90% at 0.4 mg/ml. For 5-FU, 3H-thymidine uptake was inhibited by 50% at 10 mg/ml and by 64% at 40 mg/ml. CONCLUSIONS: Mitomycin C probably does not improve the success of filtration surgery by killing fibroblasts. The ability of a brief exposure to MMC to improve filtration surgery may be due to an almost complete inhibition of proliferation. Alternatively, it may be due to sustained tissue binding, effects on other components of wound healing, such as cell migration and extracellular matrix production, or effects on the vasculature. A 1 minute exposure may be as effective as a 5-minute exposure. PMID- 1407981 TI - Intraocular pressure reduction in normal-tension glaucoma patients. The Normal Tension Glaucoma Study Group. AB - BACKGROUND: In a collaborative study, patients with untreated normal-tension glaucoma were randomly assigned to a marked intraocular pressure reduction group or to a no therapy group. It was anticipated that medical therapy and laser trabeculoplasty would generally not achieve adequate pressure lowering and that fistulizing surgery would be required. This hypothesis was examined using current observations in the study. METHODS: Patients randomized to the therapy group had a pressure reduction of at least 30% from their last prerandomization level. This was achieved within 6 months by means of fistulizing surgery or with pilocarpine and/or laser trabeculoplasty. Beta-blockers and adrenergic agonists were excluded from both eyes. RESULTS: Of 30 patients with documented stable 30% pressure reduction, 17 (57%) achieved this with topical medication and/or laser trabeculoplasty: 8 with pilocarpine alone, 2 with laser trabeculoplasty alone, and 7 with laser trabeculoplasty after initial topical medication. The remaining 13 (43%) patients required a single fistulizing procedure. There was no statistically significant difference between the mean follow-up time for the nonfistulized group (533.8 +/- 437.6 days) and for the fistulized group (502.7 +/ 344.7 days). Both treatment groups had similar baseline profiles. CONCLUSION: Marked pressure reduction can be achieved and maintained on a long-term basis by means other than fistulizing surgery in a large proportion of patients with untreated normal-tension glaucoma. PMID- 1407983 TI - Temporomandibular joint diskectomy. No positive effect of temporary silicone implant in a 5-year follow-up. AB - The purpose of this study was to evaluate the long-term clinical and radiologic effects of a temporary silicone implant after diskectomy of the temporomandibular joint. Forty-three temporomandibular joints in 43 patients with painful disk displacement underwent a diskectomy. A sheet of medical-grade silicone was temporarily placed in 22 patients; 21 patients did not receive an implant. The patients were clinically and radiologically examined 5 years after surgery. On the basis of symptoms and jaw function, they were classified as having good (30 patients), acceptable (8 patients), and bad (5 patients) results. All the patients with bad results and five of the eight patients with acceptable results had received implants. Erosive changes of the condyle or fossa were seen radiographically at follow-up in eight patients, each of whom had received an implant. No positive clinical or radiologic effects of the implants could be identified. The use of a temporary silicone implant after diskectomy of the temporomandibular joint in patients with internal derangement should be seriously questioned. PMID- 1407984 TI - HIV parotid gland lymphoepithelial cysts. Review and case reports. AB - Lymphoepithelial cysts of the parotid gland are frequently associated with cervical lymphadenopathy. These unique cysts have recently been recognized as another manifestation of HIV disease. Proliferation of lymphocytes and salivary gland tissue contained within intra-parotid lymph nodes is observed. The lymphoepithelial cyst is the end product. Ultrasound imaging serves as an excellent technique to demonstrate the existence of these cysts. PMID- 1407985 TI - Steroid acne after orthognathic surgery. AB - Steroid acne is a common unwanted effect in patients undergoing corticosteroid therapy. Eight women in a series of 1276 adult patients had acne after orthognathic surgery in which short-course parenteral corticosteroid therapy was used to reduce postoperative swelling. Steroid-induced acneiform eruption is different from acne vulgaris in that the former usually resolves on its own, without scar formation, after withdrawal of the drug. PMID- 1407986 TI - Idiopathic trigeminal neuralgia complicated by lingual nerve dysesthesia. AB - The treatment of facial pain disorders has become a multifaceted discipline that involves numerous scientific fields. Diagnostic and treatment modalities may be beneficial to the patient but at times may also complicate the problem and compromise the outcome. We present an interesting case of left trigeminal neuralgia complicated by unassociated lingual nerve dysesthesia. PMID- 1407987 TI - Failure of an endodontic implant. Complications of removal and treatment. AB - The principal goal in the development of endodontic implants is to improve the stability of periodontally and traumatically compromised teeth. When excessive forces exist and periodontal conditions are suboptimal, however, the system breaks down and ultimately fails. We report such a failure, a sequela of which contributed to subsequent fracture of the mandible. The patient's hospital course and complications of treatment are discussed. PMID- 1407988 TI - Salivary gland involvement in autoimmune thyroiditis, with special reference to the degree of association with Sjogren's syndrome. AB - From a total of 63 patients with autoimmune thyroiditis, 19 cases were further investigated to determine the degree of concomitant morphologic and functional salivary gland changes. For comparison, 21 of a total of 28 cases of primary Sjogren's syndrome were also examined. Of the 19 cases of autoimmune thyroiditis, 11 showed various degrees of salivary gland involvement on the basis of an analysis of lower lip salivary gland biopsy specimens, scintigraphy of the parotid, and unstimulated whole sialometry. Six of these cases fulfilled the criteria of primary Sjogren's syndrome. A remarkably high proportion of dark staining acini was observed in the lower lip biopsy specimens of our patients with thyroiditis (8 of 19, 42%) and less among our patients with primary Sjogren's syndrome (5 of 21, 24%). We conclude that significant involvement of salivary glands may occur in cases of autoimmune thyroiditis, which indicates that common mechanisms may frequently be operative in the development of thyroid and salivary gland immune disease. PMID- 1407989 TI - Clinical response to levamisole in thirty-nine patients with erythema multiforme. An open prospective study. AB - Patients with erythema multiforme (EM) often have chronic or recurring oral lesions that cause intense pain and interfere with a variety of functions including eating and speech. Previous studies suggest that levamisole restores to normal the function of phagocytes and T lymphocytes, and activates the inflammatory response. In our previous double-blind study 8 of 13 patients with EM had a decrease in severity and frequency of attacks. The purpose of this open prospective study was to evaluate short-term and long-term clinical efficacy of levamisole in patients with mucocutaneous EM. Thirty-nine patients with mucocutaneous EM seen in the Oral Medicine Clinic, School of Dentistry, University of California-San Francisco, comprised our study group. Levamisole was used alone in 17 patients or in combination with prednisone in 22 patients and was given as a single dose of 150 mg/day for 3 consecutive days. Thirty-one patients showed a complete response from levamisole (alone in 13 and in combination with prednisone in 18). Four showed a partial response of signs and symptoms, and four others had no benefits from levamisole whether alone or in combination. The most common side effects from levamisole were skin rash, tiredness, weakness, myalgia, taste change, and insomnia. PMID- 1407991 TI - Dental and oral findings in patients with familial dysautonomia. AB - Familial dysautonomia is an inherited autosomal recessive disease found almost exclusively in Ashkenazi Jews. It is characterized by selective damage to the sensory, motor, and autonomic peripheral nervous system. The main clinical features include decreased pain sensation, impaired temperature and blood pressure regulation, lack of tearing, absent tendon reflexes, and fungiform papillae on the tongue. The purpose of this study was to explore in depth and to verify the oral and dental status in familial dysautonomia. Twenty-two patients and 44 match-paired healthy persons of Ashkenazi descent were examined. Patients and parents had only little concern for their oral condition. Caries prevalence was lower than normal and plaque accumulation increased in all patients. Dental trauma was found in 59% of the patients, and 32% showed orodental self mutilation. Dental age was within normal range, and dental arch measurements implied proportionally small jaws and little crowding. The low caries rate may be related to the known "hypersalivation" in familial dysautonomia and/or a possible change in the salivary composition and content, caused by chronic autonomic denervation. PMID- 1407990 TI - Jaw and other orofacial pain in patients receiving vincristine for the treatment of cancer. AB - This prospective cohort study investigated orofacial pain occurring as a manifestation of vincristine neurotoxicity. Forty cancer patients (28 to 63 years of age) receiving vincristine were given baseline interviews and orofacial examinations, which were repeated weekly for 7 weeks of treatment. Twenty-two patients (55%) had neurotoxicity manifesting as orofacial pain. Onset was usually 3 days after vincristine administration; mean duration was 2 days. Twenty patients (50%) were affected in the first week: nine (22%) with severe and five (12%) with moderate pain. Symptoms were mild and infrequent in subsequent weeks. Eighteen control patients receiving chemotherapy without vincristine had no comparable orofacial symptoms. Multiple sites in the distribution of the trigeminal and glossopharyngeal nerves were affected: primarily the temporomandibular joint, mandible, throat, ears, and mandibular teeth. The frequency of orofacial pain increased with younger age. Pain was significantly associated with smaller body surface area (p less than 0.05), indicating a dose related toxicity, and with sociodemographic variables including smoking (p less than 0.05). PMID- 1407992 TI - Chronic candidiasis, enamel hypoplasia, and pigmentary anomalies. AB - This report describes a young male patient who had enamel hypoplasia, persistent oral candidiasis, skin hyperpigmentation, and vitiligo, and was thus suspected of having candidiasis endocrinopathy syndrome. The clinical and laboratory investigations employed to confirm the diagnosis are detailed. PMID- 1407993 TI - Effects of pilocarpine on salivary flow in patients with Sjogren's syndrome. PMID- 1407994 TI - Epithelioid angiosarcoma of the maxilla. A case report and review of the literature. AB - Epithelioid angiosarcoma is a rare vascular tumor composed of a proliferation of cytologically malignant epithelioid endothelial cells. These tumors are fully malignant and can pursue a rapidly progressive course. A case of primary epithelioid angiosarcoma of the maxilla is presented. Also discussed is a review of the literature with emphasis on the concept of epithelioid endothelial cell tumors. PMID- 1407995 TI - Natural history of HIV-associated salivary gland disease. AB - To describe the natural history of HIV-associated salivary gland disease, which is characterized by enlarged major salivary glands and/or xerostomia in HIV infected persons, we assessed 22 patients at an initial and follow-up examinations (median span of examinations, 15 months). Sixteen patients (73%) had bilateral parotid gland enlargement, 17 had symptoms of dry mouth, and 11 had both conditions. Parotid gland enlargement remained unchanged in 10 patients, it progressed in 2, and it regressed in 4 during treatment with zidovudine or steroids. Those patients with parotid gland enlargement had a significantly lower mean stimulated parotid flow rate (0.27 ml/min/per gland) than a control group of HIV+ persons without salivary gland disease (0.48 ml/min/per gland) (p less than 0.05), whereas the mean unstimulated whole salivary flow rates did not did not differ significantly between the two groups. The mean salivary flow rate of the study group did not change during the observation period. When HIV-associated salivary gland disease was diagnosed, 5 patients (23%) had AIDS, and at follow-up 10 (46%) had AIDS. Seven of these had Kaposi's sarcoma. The mean peripheral blood CD4 cell count was 280 and 225 per mm3 at the initial and follow-up examinations, respectively. The corresponding CD8 counts were 1138 and 900. The pathogenesis of HIV-associated salivary gland disease may include hyperplasia of intra-parotid lymphoid tissue. Because HIV-associated salivary gland disease can clinically resemble Sjogren's syndrome, the differential diagnosis of bilateral parotid enlargement should include HIV infection. PMID- 1407996 TI - A non-Hodgkin's lymphoma in the buccal mucosa. A case report. AB - Non-Hodgkin's lymphomas are tumors of the immune system that uncommonly evolve as primary lesions of the oral cavity. A case of a primary lymphoma in the right cheek that had invaded the surrounding tissues is presented. PMID- 1407997 TI - B-cell lymphoma presenting as a midfacial necrotizing lesion. AB - A case of midfacial necrotizing lesion (midline nonhealing granuloma) is reported. Paraffin- and frozen-section immunocytochemistry suggested a tumor of B cell lineage and was confirmed by Southern blot analysis that disclosed an immunoglobulin heavy chain gene rearrangement with no evidence of T-cell receptor genetic aberration. The tumor was of B-cell lineage despite the tumor site and the angiocentric pattern, which are typically seen with peripheral T cell lymphoma with this presentation. PMID- 1407998 TI - More about neuralgia-inducing cavitational osteonecrosis (NICO) PMID- 1407999 TI - Vascular changes in the dental pulp in the hypercholesterolemic miniature swine. AB - The aim of this study was to evaluate the effect of hypercholesterolemia and a cholesterol-lowering diet on the blood vessels of dental pulp. Eighteen miniature swine were assigned to three different groups on the basis of their diets: hog finisher; hog finisher with added fat and cholesterol, or hog finisher with added fat and cholesterol supplemented with grapefruit pectin. The cholesterol levels were monitored monthly for the duration of the experiment. Biopsy specimens of the aorta, coronary arteries, kidneys, and mandibular incisor teeth were prepared for histologic examination. The degree of narrowing of the central pulpal arterioles was measured with a Bioquant II digitizer attached to an Apple IIe computer and a Nikon Labophot light microscope. A few (9.8%) of the pulpal arterioles of the swine on a high-cholesterol diet had atheromatous plaques, but no complete vascular obstructions were observed. No degenerative changes were observed in any of the dental pulps examined. PMID- 1408000 TI - Bone and root resorption. Effects of the force developed during periodontal ligament injections in dogs. AB - The purpose of this study was to determine the role of the pressure generated during the intraligamentary injection technique on the occurrence of root and bone resorptions in dogs. Five beagles were used in the study, and interventions were scheduled to provide observation periods at 7, 25, and 45 days. One hundred five sites on the dogs were divided into three groups: (1) those subjected to needle penetration; (2) those subjected to saline solution injection; and (3) the control sites. Injections were made with a specially designed syringe equipped with a miniaturized force transducer. The dogs were then killed, and block sections of the sites were made and treated in accord with standard histologic procedures. The mean number of osteoclasts and odontoclasts was calculated for each group, and the mean value of bone and tooth resorption angle was measured. Data were then analyzed statistically. Results showed that, at 7 days, needle penetration and saline solution injection caused osteoclastic activity and bone resorption; the number of osteoclasts and the extent bone resorption were greater in the group that received the injection of saline solution. No difference was found for the odontoclastic activity and tooth resorption. A correlation was found between the force developed during injection, the mean number of osteoclasts, and the mean angle of bone and tooth resorption. At 25 and 45 days, healing had occurred. These findings suggest that fluid pressure within the periodontal ligament is sufficient to initiate osteoclastic, reversible bone resorption. PMID- 1408001 TI - The significance of idiopathic osteosclerosis found in panoramic radiographs of sporadic colorectal neoplasia patients and their relatives. AB - Osteosclerotic lesions in the mandible are reported with increased frequency in patients with colorectal neoplasia. Panoramic radiography has been suggested to detect high-risk patients among relatives of patients with hereditary adenomatous disease and sporadic colorectal cancer. The present study was undertaken to compare the incidence of idiopathic osteosclerotic lesions in patients with sporadic colorectal cancer and their first-degree relatives with the incidence in the general population and to determine whether panoramic radiographs are a reliable method to screen for early detection of risk of colorectal cancer. A total of 283 patients were interviewed and radiographically examined. Idiopathic osteosclerosis appeared in significantly increased incidence only in patients with colorectal cancer or adenomas and a first-degree relative with CRC (chi 2 = 7.214; p less than 0.01, and chi 2 = 4.1827; p less than 0.05 respectively). The incidence was not increased in first-degree relatives of patients with colorectal cancer or adenoma. Therefore panoramic radiographs cannot be the only screening tool for early detection of patients at high risk of colorectal cancer. PMID- 1408002 TI - Carcinoma arising in a dentinogenic ghost cell tumor. AB - A 13-year-old black girl was referred for evaluation of a nonhealing extraction site of 2 years' duration. Radiographs revealed a large, irregularly shaped, mixed radiolucent/radiopaque lesion that occupied almost the entire left area of the maxilla and crossed the midline. Microscopic examination revealed irregular dentinoid material with odontogenic epithelium that exhibited ghost cell keratinization and anaplastic changes. The patient underwent a hemimaxillectomy, and 7 years after surgery she appears to be free of disease. PMID- 1408003 TI - Evaluation of radiopaque denture liner. AB - Radiopacity is needed in polymeric biomaterials to facilitate noninvasive detection. Permanent denture liner material with barium sulfate filler is nearly as radiopaque as aluminum and would be useful in radiographic identification. If 1 mm to 3 mm thicknesses are used, it should be easily observable radiographically. PMID- 1408004 TI - Unusual cause of mandible fracture. PMID- 1408005 TI - Multiple supplemental premolars. PMID- 1408006 TI - Arrested tooth development after therapeutic radiation. PMID- 1408007 TI - Evaluation of prognosis and survival of the HIV-infected patient. AB - HIV disease, once considered an acute disease with a 100% mortality rate but a very short symptomatic stage, has begun to emerge as a preventable, treatable, chronic disease. Interactions between patients, dentists, and physicians are essential to gain the information necessary to provide appropriate dental care for both short-term and long-term survivors. The prognosis and survival time of the dental patient may influence treatment protocols and necessitate modified dental procedures. Certain clinical and laboratory parameters, which may be useful indicators of disease progression, need to be recognized by the dental clinician. These parameters include systemic signs, symptoms, and serologic data as well as intraoral manifestations associated with HIV disease. Although a perfect classification system for progression of HIV disease does not exist, trends among larger cohorts may enable health care providers to estimate the prognosis and survival of HIV-infected patients on an individual basis. This article presents clinical and laboratory parameters that indicate HIV disease progression. Providers who care for HIV-infected patients need to consider these parameters to establish an appropriate and flexible treatment plan based on changes in the patient's medical status. PMID- 1408008 TI - Computer-aided analysis of intraoral ulcerative lesions. AB - At the present time there is no objective method to evaluate oral ulcerative lesions for degree of inflammation, surface area, or other parameters of healing. The capability of infrared photography to uniquely image the inflammatory process associated with oral lesions and the use of image-processing technology for parameter analysis was investigated. Lesions were compared cross-sectionally and over time for area of tissue degeneration, active inflammation, and intensity of inflammation with respect to adjacent tissue. Eight subjects were available for study. Standard black and white, color, and black and white infrared photographs were taken in accord with study protocols. A reflectance standard was included in each photograph to normalize the background intensity. A video camera was used to enter the data into a microcomputer image processing system. Quantitative data obtained included area of ulceration and erythematous halo, inflammatory intensity changes over time, and intensity with respect to adjacent tissue. This computer-aided photographic technique was able to quantify healing progression and intensity parameters associated with intraoral inflammatory lesions. PMID- 1408009 TI - Survey of the medical history questionnaire. AB - The purpose of this study was to examine and to compare the type of information requested on representative health history questionnaires commonly used by the dental profession. Samples of medical history questionnaires were obtained from American and Canadian dental schools, commercial vendors, and the American Dental Association. Results indicated that more than 140 questions have been included on questionnaires and more than 92% of these appeared in some type of yes-or-no format. The number of questions per form ranged from 32 to 88, with an average of 58 items. Although there was wide variation in the range of information requested, the 25 most frequently asked questions occurred in 70% of the forms. The majority of questions focused on noninfectious disease conditions that affect the cardiovascular system and major organ functions, allergies, and blood disorders; infectious diseases such as hepatitis, tuberculosis, mumps, and venereal disease; and health care status and special treatment considerations. PMID- 1408010 TI - Squamous cell carcinoma of the upper aerodigestive tract in patients 40 years of age and younger. AB - Oral squamous cell carcinoma in patients 40 years of age and younger has been noted to be infrequent. The incidence is not as noticeable because the majority of oral cancers are diagnosed during the later decades of life. This study was undertaken to evaluate the incidence, site predilection, etiologic factors, and modes of treatment and to compare these results with available data on this topic. Of 1387 cases of oral and pharyngeal squamous cell carcinoma diagnosed from 1968 to 1989 at University Hospital and affiliated institutions, 28 occurred in patients under 40 years of age. When these lesions were staged according to the American Joint Committee for Cancer Staging, we found 6 stage I lesions, 3 stage II, 2 stage III, and 11 stage IV. Six lesions could not be staged from information available in the patient records. Present data corroborate the national average of 1% to 3% of cases of oral squamous cell carcinoma found within the 40 and under age group. PMID- 1408011 TI - Multicenter evaluation of temporomandibular joint Proplast-Teflon disk implant. AB - Seven oral and maxillofacial surgeons from all U.S. American Association of Oral and Maxillofacial Surgeons districts participated in a retrospective study of Proplast II Teflon interpositional implants that were placed after meniscectomy in 680 TMJs (465 patients) and followed from 6 to 76 months. At longest follow-up a relatively high number (85.9%) 584 of 680 implants were in place with an average weighted follow-up of nearly 32 months. Of these 584 joints, a very high number, 540, (92.4%) were asymptomatic, however, 224 asymptomatic and 25 symptomatic joints with the implants in place exhibited some degree of condyle resorption that included 45 with malocclusion. In the worst case scenario, if condylar resorption is indicative of a worn Proplast II Teflon interpositional implant, then 364 (54%) of the 680 implants may fail. Failure rates per year range from Vitek's reported 3% to an average 18% clinician report in the literature. Higher rates are reported by individual clinicians, and our recent in vitro wear tests of Proplast II Teflon interpositional implants suggest an in vivo service life of only 3 years. Because no one has reported follow-up beyond 5 years, the long term performance and survival of any of these implants is doubtful. Asymptomatic patients should be evaluated yearly with tomography, CT, or MRI. Symptomatic patients should be evaluated every 4 to 6 months. Implant removal should be recommended if occlusal changes or condyle/fossa articular bone changes are active past the time of expected remodeling from surgery. This report summarizes the success/failure incidence from the literature and makes recommendations on follow-up, removal, and repair surgery. PMID- 1408012 TI - Cerebrospinal fluid leak associated with proplast implant removal from the temporomandibular joint. AB - Severe bone erosion within the temporomandibular joint reconstructed with polytetrafluoroethylene implants is a well-recognized phenomenon. Although erosion into the middle cranial fossa has been reported, we know of no report of dural disruption with cerebrospinal fluid leakage. We report a case of cerebrospinal fluid leak noted at the time of PTFE implant removal and its subsequent management. Perforation of the contralateral glenoid fossa and its reconstruction is also reported. PMID- 1408013 TI - Healing after dental extractions in men with HIV infection. AB - To determine the incidence of delayed healing after dental extractions in men with HIV infection, a retrospective audit was conducted of all extractions performed in a dedicated dental clinic over a 26-month period. The incidence of delayed healing in patients with HIV was compared with the incidence in those patients without HIV. Eighty men with HIV had 163 teeth extracted, which resulted in five dry sockets (3.01%). Thirty-six men thought not to have HIV had 70 extractions and three dry sockets (4.28%). All three dry sockets in the control group occurred in men who had tested negative for HIV antibodies in the year before their extraction. There were no other incidents of delayed healing. These findings contrast with other reports since they reveal no increase in delayed healing after extractions in men with HIV and do not support recommendations that prophylactic antimicrobials are required for extractions in this group of patients. PMID- 1408014 TI - Effect of extraction of partly erupted third molars on subgingival microorganisms. AB - This study was made to investigate the effect of extraction of third molars on subgingival microbes in 39 generally and gingivally healthy men with an average age of 20.2 years (SD 0.9). Microbial samples were taken from the pericoronal space of symptom-free partly erupted lower third molars and from the adjacent gingival pockets of the second molars. The samples were cultivated anaerobically. All partly erupted third molars were extracted from 20 subjects. A control group of 19 subjects was left untreated. Microbe sampling was repeated 2 and 5 months postoperatively with highly significant results. It was shown that at baseline the number of black-pigmented gram-negative bacteria and Fusobacterium species was more frequent in third molar than in second molar sites. The total bacterial count decreased significantly at the second molar sites after extraction of the third molars when compared with the control group. Before the extractions, black pigmented gram-negative bacteria were detected in 45% of the test subjects and Actinobacillus actinomycetemcomitans in 20%. The respective postoperative figures were 30% for black-pigmented gram-negative bacteria and 10% for Actinobacillus actinomycetemcomitans. Capnocytophaga species were not affected by the extractions. The findings suggest that erupting third molars may harbor harmful bacteria that can be reduced by eradicating the foci. PMID- 1408015 TI - Temporomandibular joint dysfunction syndrome: a close association with systemic joint laxity (the hypermobile joint syndrome) PMID- 1408016 TI - Pre-operative laboratory assessment of hemostasis for orthognathic surgery. PMID- 1408017 TI - Drugs used in the management of trigeminal neuralgia. AB - Management of trigeminal neuralgia, a severe facial pain, remains difficult. All patients are initially treated with drugs. Since the seventeenth century more than 40 different preparations have been used; some of these, although effective, had toxic side effects. The most useful drugs at present are carbamazepine, phenytoin, baclofen, and clonazepam. A new drug, oxcarbazepine, is showing therapeutic promise. The most common reason for therapeutic failure with antineuralgic drugs is inadequate dosage. We review here the pharmacokinetics, side effects, possible drug interactions, plasma and serum therapeutic concentrations, and the available formulations of each drug. On the basis of these considerations and clinical reports describing the use of these drugs, we make dosage recommendations to enable the practitioner to individualize therapeutic regimens. PMID- 1408018 TI - Immunodiagnosis in oral candidiasis. A review. AB - Detection of anti-Candida antibodies in sera and saliva of patients with oral candidiasis has been regarded as a valuable laboratory technique in the diagnosis of the lesion. However, despite considerable research, the value of candidal immunodiagnosis remains controversial. Conflicting conclusions about the sensitivities and specificities of these techniques as applied to human sera and saliva have appeared. These controversies have arisen because of the use of different antigen preparations and immunologic techniques. For the present, the use of purified cytoplasmic protein antigen of Candida albicans and the ELISA technique seems to be the most reliable laboratory method. PMID- 1408019 TI - Close association of HLA-B51 in persons with recurrent aphthous stomatitis. AB - The HLA typing profile of 26 Israeli subjects with recurrent aphthous stomatitis (RAS) was examined and compared with that of 100 healthy control subjects. HLA B51 was found in six subjects (23%) with RAS and in nine control subjects (9%) (p < 0.05). HLA-Cw7 was found in six subjects with RAS (23%) and in five control subjects (5%) (p < 0.01). Eleven subjects had first-degree relatives who had RAS. Because a high frequency of HLA-B51 has been found in Behcet's syndrome and aphthous stomatitis is part of this syndrome, it is suggested that in some subjects with RAS the entire syndrome may actually develop in the future. PMID- 1408021 TI - Smokeless tobacco use prevents aphthous stomatitis. AB - Aphthous stomatitis is a common, recurrent, painful ulcerative condition of the oral mucosa. Cigarette smoking has been reported to protect against aphthous ulcers. To determine whether smokeless tobacco use also protects against aphthous ulcers, we examined the oral mucosa in 1456 professional baseball players, about half of whom were smokeless tobacco (ST) users. After controlling for the confounding effects of age, race, cigarette smoking, alcohol consumption, and dental hygiene practices, ST use was found to significantly reduce the risk of aphthous ulcers among these healthy young men (odds ratio = 0.4; p = 0.04). It has been suggested that cigarette smoking prevents aphthous ulcers by causing increased keratinization of the oral mucosa, and ST may protect by the same mechanism. Alternatively, a component of tobacco that is systemically absorbed might be responsible for protecting against aphthous ulcers. If the mechanism that protects ST users against aphthous ulcers is systemic, then nicotine is the likely protective factor. PMID- 1408020 TI - Gram-negative enteric bacteria in the oral cavity of leukemia patients. AB - We examined changes in the bacterial flora in hospitalized patients with leukemia. This study placed special emphasis on enteric microorganisms and their relation to the general status of the patient. One hundred thirty bacterial cultures from 16 leukemia patients and 16 control subjects, were obtained. The organisms were isolated on MacConkey agar and identified by the API-20E system. Enteric microorganisms were isolated from 62.2% of the leukemia patients as compared with 28% from the control group (p < 0.001). The enteric positive cultures were identified as Klebsiella (42.7%), Enterobacter (18.8%), and Pseudomonas (15.6%). In contrast to the negative cultures (1342), enteric microorganisms were cultured from 2948 specimens (p < 0.005). PMID- 1408022 TI - Invasive maxillary aspergillosis after dental extraction. Case report and review of the literature. AB - Paranasal sinus aspergillosis has usually been considered a rare disease, but it is seen more frequently in both immunocompromised and immunocompetent persons. Invasion may reach the sinuses via the nose or from the mouth after dental procedures. Even though the infection is usually limited to one or more sinuses, it may in certain cases extend to vascular or intracranial structures with a fatal outcome. In these cases, aggressive treatment is justified. We report a case of maxillary sinus aspergillosis that developed after dental extraction. Attention should be given to this possibility even after an apparently uncomplicated dental extraction. PMID- 1408023 TI - Immunohistochemical detection of ras 21 in oral squamous cell carcinomas. AB - The expression of the ras p21 in oral squamous cell carcinoma was examined immunohistochemically with the use of a monoclonal antibody NCC-RAS-001 with the avidin-biotin-peroxidase complex method. The expression of ras p21 product was detected in 65.7% (44 of 67 cases) of cancer patients. On the basis of the degree of histologic differentiation of the cancer cells, the incidence of ras p21 was found to be as follows: 63.4% (26 of 41 cases) were well differentiated; 86.7% (13 of 15 cases) were moderately differentiated; and 45.5% (5 of 11 cases) were poorly differentiated. The highest incidence was found in patients in their sixties--80.0% (16 of 20 cases). The incidence decreased to 40% in patients over 80 years of age. The incidence of ras p21 on the basis of location was as follows: 81.8% (9 of 11 cases) involved the buccal region, 70.6% (12 of 17 cases) were in the gingiva, and 55.0% (11 of 20 cases) were in the tongue. PMID- 1408024 TI - Evaluation of the carcinogenic potential of toluidine blue O in the hamster cheek pouch. AB - Toluidine blue O has been shown to have clastogenic and mutagenic effects when tested in vitro, suggesting that it may be a carcinogen. Because this might compromise its use for cancer screening, the carcinogenic potential of this dye was investigated in the hamster cheek pouch, an established in vivo carcinogenesis model. Male hamsters were divided into seven groups at age 5 weeks. The right pouches of four groups were painted three times weekly with 2% toluidine blue or the vehicle for toluidine blue, in conjunction with submaximal applications of 9,10-dimethyl-1,2-benzanthracene (DMBA) (groups II and III, 0.5% twice weekly), and groups IV and V, 0.1% three times weekly). The right pouches of two groups received DMBA only (group I, 0.5% three times weekly, the standard maximal amount, and group VI, 0.1% three times weekly). Group VII received toluidine blue (right pouches) and toluidine blue vehicle (left pouches) three times weekly. The extent of carcinomas and other abnormalities (scored histologically) did not differ among groups receiving the same amount of DMBA with and without toluidine blue or vehicle, and no abnormalities were seen in the pouches from group VII. These results demonstrate no effect of toluidine blue as a carcinogen, cocarcinogen, or promoter. PMID- 1408025 TI - Silver-binding nucleolar organizer region proteins as a possible prognostic indicator in oral submucous fibrosis. AB - Silver-binding nucleolar organizer region proteins (AgNORs) were counted in sections from formalin-fixed, paraffin-embedded tissue blocks of oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (SCC). Moderately advanced and advanced cases OSMF, and well-differentiated and poorly differentiated cases of SCC, were studied with respect to the relation between AgNOR counts and histologic grading. Normal oral mucosa collected from age- and sex-matched subjects constituted the control group. The pooled mean (+/- SD) AgNOR counts were as follows: normal mucosa, 2.50 +/- 0.52 (n = 5); moderately advanced OSMF, 5.24 +/- 1.23 (n = 10); advanced OSMF, 7.26 +/- 1.12 (n = 10); well differentiated SCC, 8.29 +/- 1.47 (n = 5); and poorly differentiated SCC, 9.49 +/ 0.74 (n = 5). The pooled mean AgNOR counts in advanced OSMF were higher than in moderately advanced cases (t = 3.84; p < 0.005) and those in poorly differentiated SCC were higher than those of well-differentiated SCC, although the comparison was not significant in the latter (t = 1.63, p > 0.10). AgNOR counts could hold promise for predicting the biologic behavior of OSMF because this study demonstrated a correlation with clinical and histologic grading. PMID- 1408026 TI - Simple bone cyst. A clinical and histopathologic study of fifteen cases. AB - Nineteen simple bone cysts found in 15 patients were studied by classifying them into younger and older age groups. The clinical, radiographic, and histopathologic features of 11 cysts in the younger group of 10 patients were consistent with those of previous reports. Among patients in the older age group, female predominance (80% vs 30%), involvement of the maxilla (25% vs 0%), multiple occurrence (60% vs 10%), simultaneous presence of radiopaque fibro osseous lesions or hypercementosis (63% vs 0%), and loss of lamina dura of related teeth (83% vs 14%) resulting in exposure of their roots on surgical intervention were the characteristic features. PMID- 1408027 TI - Effects of chronic Candida albicans in the hamster cheek pouch. AB - Sixty-four adult male hamsters had a suspension of either C. albicans (UO1) or C. albicans (ATCC 10261) placed in their cheek pouches once a week for up to 9 months. Four hamsters from both experimental groups, along with two untreated control hamsters, were killed at monthly intervals after the initial inoculation. Sections taken from the hamsters and examined in the light microscope showed that all experimental pouches had some or all of the following localized changes: inflammation and increased vascularity of the connective tissue; epithelial inflammation and microabscesses; hyperkeratosis; and isolated rete ridges similar to those in control pouches. C. albicans, usually the yeast form, was present on the exposed surface and between hyperplastic keratin squames. There was no hyphal invasion of the epithelium. Rather than being a true long-term study of chronic infection by C. albicans, the changes seen were probably the result of repetitive, more short-term responses after multiple inoculations. PMID- 1408028 TI - Another look at root canal instrumentation. AB - Several aspects of root canal instrumentation need additional research. Various factors must be considered in an analysis of instrumentation of the root canal system: the dentin that is cut; the technique used to cut it; the design of the instruments; the material and manufacturing process used to make the instruments; the irrigant used during the procedure; and the anatomic configuration of the root canal system. An analysis of these factors clearly indicates that existing root canal instruments and techniques are less than ideal and, in fact, do not accomplish what is expected of them. Root canals must be properly, but, at the same time, destructive and unnecessary removal of dentin should be kept to a minimum. The Flex-R and Canal Master instruments were developed to address some of the shortcomings of existing instruments and techniques. More scientifically based research is needed to fully evaluate these new instruments and techniques and to develop future instruments. PMID- 1408029 TI - Dual wavelength spectrophotometry as a diagnostic test of the pulp chamber contents. AB - The purpose of this in vitro study was to determine the feasibility of using dual wavelength spectrophotometry to identify teeth with pulp chambers that are either empty, filled with fixed pulp tissue, or filled with oxygenated blood. In phase I of the experiment, a human third molar was prepared so that its pulp space could be filled with oxygenated blood and later emptied. In phase II, the lower jaw of a beagle dog was removed and placed in formalin, thereby fixing the pulps of the teeth. The pulp of the right canine was removed via an apical approach, and attachments were placed in a similar position to those on the human tooth, to allow filling and emptying of the pulp space. Cavit was placed over the exposed fixed pulp in the left canine. Ten readings, which were separated by light source and detector removal and replacement, were taken of the right canine pulp space when it was empty or filled with oxygenated blood, or the left canine pulp space when it was filled with fixed tissue. Distinct and reproducible changes were measured for pulp spaces filled with air, tissue, or oxygenated blood. In phase III, simulated pulp testing on a dog tooth model was performed. Blood was introduced into the root canal space, the chamber was rinsed with water and replaced with air, according to a predetermined code. Spectrophotometer readings were recorded. The identification of pulpal contents was correctly determined in all 20 of the predetermined conditions. The findings indicate that continuous wave spectrophotometry may become a useful pulp testing method. PMID- 1408030 TI - Magnetic resonance spectroscopy of inflammation associated with the temporomandibular joint. AB - Noninvasive early recognition and treatment of temporomandibular joint dysfunction remains a diagnostic challenge. This pilot study evaluated the use of phosphorus 31 magnetic resonance spectroscopy with magnetic resonance imaging to measure alterations in pH and high-energy phosphate metabolite ratios of muscle that is adjacent to an inflamed temporomandibular joint. Ten New Zealand white rabbits were used in this study. Two animals were used to develop signal acquisition protocols and to ensure that stable baseline data could be measured. In each of the eight animals used in the experiment, one temporomandibular joint was injected with a suspension of silica particles and the contralateral joint served as a control. Data were collected from control and experimental joints on days 0, 7, 14, 21, and 28, after the injection. At the end of the study, temporomandibular joints were block resected and histologically examined to confirm the presence of an inflammatory response. Results indicated that pH and metabolite ratios could be obtained by 31P-magnetic resonance spectroscopy. Changes in pH and some metabolite ratios in experimental joints showed statistical significance (p < 0.001). Differences were seen on day 2 and day 7 (p = 0.040 and p = 0.008, respectively) in the phosphocreatine/alpha-adenosine triphosphate ratios. This contrasts with phosphocreatine/beta adenosine triphosphate ratios that showed significance that began at day 7 (p = 0.022) and continued to day 14 (p = 0.025). Histologic examination indicated that the tissue response within the joint capsule was less than the granulomatous reaction expected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408031 TI - Image resolution in the midsagittal plane of the Orthopantomograph-10 using Lanex regular and T-Mat G screen-film combination. AB - Image resolution was measured in the midsagittal plane of the Orthopantomograph 10 with the use of Lanex regular and T-Mat G screen-film combination. A thin platinum edge phantom was used to obtain images for calculation of the edge response functions. Subsequently, line spread functions and modulation transfer functions of the system were calculated. Noise equivalent passband values, which were expressed in line pairs per millimeter, were derived to describe the image resolution. The noise equivalent passband values derived in this study were generally smaller than those reported in a previous study. The width of the image layer was found to be uniform at different vertical levels. PMID- 1408032 TI - Antibiotic chain. PMID- 1408033 TI - Bilateral complete rotation of maxillary lateral incisors with dens invaginatus. PMID- 1408034 TI - Large caliber bullet stopped by pyriform rim. PMID- 1408035 TI - Submergence of a previously restored maxillary first molar associated with mesial tilting of an adjacent tooth. PMID- 1408037 TI - The patellofemoral joint. PMID- 1408036 TI - Historical perspectives of chondromalacia patellae. AB - Widespread misuse of the term chondromalacia has led to confusion regarding its true meaning. This term should not be used to diagnose patellofemoral pain, but to describe lesions of articular cartilage. Recent advances using stereophotogrammetry to evaluate the patellofemoral joint and its articular cartilage may lead to new insight into the etiology of these lesions. PMID- 1408038 TI - Imaging of the patellofemoral joint. AB - Abnormalities of the patellofemoral joint are one of the main problems in internal derangement of the knee. The role of different imaging modalities (plain radiographs, CT, CT/arthrograms, radionuclide scans, and MR imaging) is discussed in this article. PMID- 1408039 TI - Conservative care for patellofemoral pain. AB - Patellofemoral pain is the most common presenting complaint about the knee joint. The explanation for this pain is not entirely clear. The four schools of thought concerning the etiology are divided among explanations based on anatomy, biomechanics, and biochemistry. The treatment for the disease is compromised by the lack of a clear causative agent. Exercises, braces, activity modification, and some medications form the basic protocol for treatment. Until the etiology becomes clear, these approaches represent the only reasonable therapy. PMID- 1408040 TI - Rehabilitation of patellofemoral joint disorders. AB - Patellofemoral dysfunction may be one of the most common and troublesome maladies to affect a patient. The correct identification of the underlying causes is paramount. Once identified, an effective rehabilitation program should be implemented. The program should include stretching and strengthening as well as several other therapeutic modalities. The most successful rehabilitation program is designed to address the specific needs of the patient. PMID- 1408041 TI - Patellofemoral pain in the pediatric patient. AB - The pediatric extensor mechanism is subject to a variety of congenital, developmental, and traumatic disorders. Growth related factors modulate the development of patellofemoral pathomechanics. Injuries to periarticular soft tissues, apophyseal, epiphyseal, and articular cartilage are identified by meticulous history and physical examination. Diagnostic radiographs and MR imaging are invaluable adjuncts. Specific rehabilitative programs are very effective and lead to a high degree of clinical success. PMID- 1408042 TI - Arthroscopic evaluation and treatment of the patellofemoral joint. AB - Patellofemoral pain is a multifactorial problem. No single successful solution for problems related to the patellofemoral joint has been identified. One needs to consider the interaction of all of the factors affecting the extensor mechanism. Evaluation begins with a careful history, physical examination, and appropriate radiographic studies. Arthroscopy can provide additional information regarding the condition of the articular cartilage, patellar tracking, and the presence of other intra-articular lesions. Conservative treatment is the cornerstone of management and is effective in more than two-thirds of patients, making surgical treatment necessary in only a minority of instances. ALRR, although not an innocuous procedure, has an acceptably low complication rate and provides predictably good results when used in properly selected patients. PMID- 1408043 TI - Arthroscopic lateral release and the lateral patellar compression syndrome. AB - An isolated arthroscopic lateral release can provide dramatic relief of anterior knee pain in a select group of patients. We believe this procedure is indicated for patients with lateral patellar compression syndrome without significant chondrosis who have not responded to nonoperative treatment. During the procedure, care must be taken to perform a complete release and to achieve hemostasis. The postoperative rehabilitation emphasizes control of swelling, patellar mobilization, and quadriceps strengthening. We strongly agree with Schonholtz et al who report that the "lateral retinacular release is not a minor procedure and should not be performed simply because it may help and it can't hurt." PMID- 1408044 TI - The plica syndrome. AB - The plica syndrome is an uncommon pathologic entity diagnosed far too often in the setting of concomitant pathology. Medial patellar pain is more likely to be related to patellofemoral maltracking than to plica syndrome. Likewise, anteromedial joint line tenderness is more likely to be related to a meniscal tear than to a pathological plica. An accurate history and physical examination aided by appropriate ancillary tests to confirm the diagnosis are essential to avoid unnecessary surgical treatment. Conservative measures are very effective and must be emphasized before any operative procedure. When arthroscopy is indicated, a thorough examination of the entire knee joint is necessary. A plica may or may not be present. When a pathological plica is found, excision is rewarded with excellent results. Unfortunately, many normal plicae are removed simply because they are present and not because they are symptomatic or pathologic. This leads to persistent symptoms because of misdiagnosis, as well as possible complications secondary to the operation. PMID- 1408045 TI - Surgical treatment for patellar instability. AB - The initial therapy for patellofemoral pain remains conservative. Once this treatment plan fails and examination has clearly identified the cause of the patellofemoral dysfunction, surgical treatment is considered. No single procedure corrects all patellofemoral problems, and the patient's age, the causative factor, the condition of the articular surface, and the level of activity should be considered. Surgical options include lateral retinacular release, proximal realignment, distal realignment, and proximal and distal realignment. PMID- 1408046 TI - Distal realignment of the patellofemoral joint. Indications, effects, results, and recommendations. AB - Effective treatment of patellofemoral malalignment is possible with precise diagnosis. This precision must begin with a thorough history and physical examination. Both nonoperative and operative treatment are guided by the specific patterns identified. Distal realignment procedures including anteromedial tibial tubercle transfer necessitate meticulous surgical technique to achieve maximal benefit with a low rate of complications. PMID- 1408047 TI - The Maquet osteotomy. AB - First proposed in 1963, the Maquet osteotomy can be used successfully for the treatment of selected patients with patellofemoral pain. A strict patient selection process must be used to achieve optimal clinical results. The complication rate can be limited, but not eliminated, by the use of meticulous surgical technique. Further prospective clinical studies, employing both subjective and objective evaluation methods, should be performed to optimize the interpretation of the clinical results. PMID- 1408048 TI - Patellectomy. AB - We believe the patella should be preserved when possible and stress the significant use the patella has in normal knee function. Although alternative treatments can often be found, patellectomy may be indicated in selected patients to improve function and reduce pain. PMID- 1408049 TI - Patellar resurfacing for patellofemoral arthritis. AB - Knee pain referable to the patellofemoral articulation is common in the general population. It remains a troubling problem for the orthopedic surgeon. Frequently, initial therapy, involving activity modification, anti-inflammatory medications, and isometric quadriceps strengthening, is successful in relieving symptoms. Surgical intervention is normally reserved for those patients with pain that is resistant to these modalities. Unfortunately, none of the various surgical options has proved to be totally dependable, durable, or reproducible. The results of isolated patellar and patellofemoral resurfacing procedures have been guarded. Patellar resurfacing appears to be most beneficial in younger patients with severe anterior knee pain. These individuals should be clearly warned that there is a relatively high likelihood that they will require additional surgical treatment or patellectomy at a later date. Fortunately, patellar resurfacing does not preclude patellectomy from being easily performed. Patellofemoral resurfacing, however, involves more overall involvement of the knee joint. This makes patellectomy less likely to be a successful salvage procedure. Despite our observations that knees with primary patellofemoral arthritis do not do as well after total knee replacement as those with tibio femoral arthritis, this procedure remains the best treatment option. The durability and predictability of total knee arthroplasty are well documented. Its results far surpass those reported for isolated resurfacing procedures. With regard to patellar resurfacing as part of total knee arthroplasty, we recommend resurfacing all patellae. The literature, although not conclusive, lends support to this practice. Avoidance of metal-backed patellar components and special attention to technical details should decrease the complications associated with patellar resurfacing in future studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408050 TI - The patella in total knee arthroplasty. AB - Controversy persists as to whether the patella should be resurfaced in total knee arthroplasty. Can the good results of patellar cartilage against the metal femoral component be expected to endure? Attention to technique can be expected to reduce some of the complications of resurfacing, notably fracture, rupture, and instability. Component breakage results from metal-backed designs, and the causes of patellar clunks have not been fully understood. PMID- 1408051 TI - Disruptions of the extensor mechanism. AB - Extensor mechanism injuries represent a challenging problem for the orthopedic surgeon. Accurate diagnosis is essential because the best results are obtained with early diagnosis and treatment. Numerous techniques have been described for both early and late repairs. The choice of repair is dependent on the location of the tear, the time interval between injury and repair, and the degree of secondary contractures. Despite these difficulties, satisfactory results can be achieved. PMID- 1408052 TI - Complications of patellofemoral joint surgery. AB - The goal of patellofemoral surgery, as is true in any surgical procedure, is the maximum benefit with the least morbidity. It is imperative that the surgeon be aware of the potential complications of operating on the patellofemoral joint. It was with this goal in mind that this review was undertaken. Complications specific to surgical therapy for LPCS, malalignment, degenerative arthritis, and trauma were covered. Procedure-specific complications were discussed, as well as IPCS and reflex sympathetic dystrophy. Recommendations on how to avoid these complications were made. Specific treatment recommendations, where appropriate, were also put forth. PMID- 1408053 TI - [Management of congenital adrenal hyperplasia]. AB - This review deals with the current problems in the management of classical 21 hydroxylase deficiency from the fetal life to the puberty. The clinical consequences of 21-hydroxylase deficiency reflect the disordered physiology- impaired secretion of glucocorticoids and mineralocorticoids, and excessive secretion of androgens. Current therapy is intended to correct the disordered physiology by replacing mineralocorticoid and glucocorticoid hormones, thereby reducing the ACTH-driven increase in adrenal androgen secretion. Treated patients should expect a normal life span and reproductive potential. This can be achieved by careful attention to regular measurements of clinical parameters and biochemical indices of control. PMID- 1408054 TI - [Doppler echocardiography in the evaluation of left ventricular diastolic function in hypertension]. AB - Twenty-five hypertensive patients were examined using Doppler echocardiography to determine the diastolic function of the left ventricle. Twenty-two parameters were analysed and the diastolic indexes were compared with the results of a control group of ten healthy volunteers. Patients with hypertension showed significant left ventricular hypertrophy with increased left ventricular mass and dilated left atrium. Eighty-five percent of the hypertensive patients were found to have impaired diastolic function. The peak velocity of the early, and late diastolic phase and also the duration of acceleration and deceleration are considered to be necessary in the investigation of the diastolic function of left ventricle. All the other parameters can be determined using the above mentioned ones. The late diastolic transmitral flow, the atrial filling velocity, the time of deceleration and acceleration and also the time velocity integral increased significantly. However, the early diastolic filling fraction decreased significantly. The abnormalities in left ventricular diastolic function and also the atrial enlargement may be the early signs of hypertensive heart disease and therefore have a great importance in the therapy. PMID- 1408055 TI - [Diagnostic value of the determination of serum alpha2-HS-glycoprotein]. AB - Opsonic glycoprotein, alpha 2-HS-glycoprotein concentration was studied in the serum of 753 patients with various hematological, malignant, immunological, metabolic, endocrine and liver diseases and 68 healthy controls. Decreased serum alpha 2-HS-glycoprotein levels were detected in patients with acute leukemias, chronic granulocyte and myelomonocyte leukemias, lymphomas, myelofibrosis, multiple myeloma, metastatizing solid tumors, systemic lupus erythematosus, rheumatoid arthritis, acute alcoholic hepatitis, fatty liver, chronic active hepatitis, liver cirrhosis, acute and chronic pancreatitis, and Crohn's disease. Elevated levels were measured in patients with B and NANB/C hepatitis. Further decreased levels were observed in some groups with secondary infections. Serum alpha 2-HS-glycoprotein levels are affected by many factors, influencing the synthesis and elimination of the protein. The detection of serum alpha 2-HS glycoprotein concentration has no specific diagnostic value as a marker for tumors or other diseases, however, its determination can be useful for the assessment of a non-specific regulator of the host defence. PMID- 1408056 TI - [Giant pigmented nevus associated with leptomeningeal melanocytosis]. AB - A case of a thirteen-year old boy is reported with congenital pigmented nevi on the large part of the trunk and on the extremities. From his age of six generalised epileptiform convulsions were present. Owing to the suspicion of intracranial process he was examined with a negative result. He died of brain edema. On section cerebrospinal leptomeningeal melanocytosis was found beside the nevi. In addition to the clinical findings and treatment the morphological lesions are detailed too at macroscopic, microscopic and ultrastructural level discussing the possibility of the malignisation. PMID- 1408057 TI - [Acupuncture in primary care]. PMID- 1408058 TI - [Changes in bone transplantation practices in Hungary]. PMID- 1408059 TI - [Drugs registered in May 1992 (III)]. PMID- 1408060 TI - [Possibilities of immunotherapy of human tumors]. PMID- 1408061 TI - [5-year experience with BCG immunoprophylaxis in superficial bladder cancer]. AB - Our 5-year experience with BCG in the tumor stage pTis, pTa and pT1, G I-II shows a lasting remission of 88.5% (73%) in 78 (26) patients treated with BCG preparation Pasteur (Connaught) after transurethral resection. A complete remission in patients with carcinoma in situ (12 patients) could be found in 92%. The local and systemic side-effects, which are of limited duration, are tolerable, well treatable and fully reversible. PMID- 1408062 TI - [Changes in the activity of natural killer cells in superficial bladder cancer during intravesical BCG therapy]. AB - Alteration of natural killer (NK) activity from the peripherial blood was examined in the patients with superficial bladder cancer during two years between 1989-1991. The natural killer cell activity in patients with superficial bladder cancer was significantly depressed that activity was found in normal controls (P less than 0.01). 23 patients received intravesical BCG immuntherapy and NK activity was detected in the same patients 72 times in different period during the therapy. The authors decided that the activity of NK cells alters in BCG therapy. Increase of NK cells activity in the most common way of this alteration but many different type of this change is possible. The lower dose BCG (120 mg) often induce augmentation of NK activity but high dose BCG (200 mg) more frequently caused depressed activity of NK cells. The authors didn't find direct connection between therapy effect and NK activity but they found significantly less NK activity (P less than 0.03) in the patients who are in relapse. According to their opinions the role of natural killer cells in the antitumor effect of BCG can not be excluded. They recommended more immunological investigations to clear up the anticancer effect of BCG immuntherapy. PMID- 1408063 TI - [Rhabdomyoma of unusual manifestation]. AB - According to our knowledge in adult pericardial effusion has never been reported to be present in cases of cardiac rhabdomyoma. We present the history of an adult patient with pericardial effusion due to cardiac rhabdomyoma. PMID- 1408064 TI - [In memory of the Red Cross Professoral College of 1956]. PMID- 1408065 TI - [Otorhinolaryngology in Hungary at the turn of the century]. PMID- 1408066 TI - [Retrospection on health care]. PMID- 1408067 TI - [Clinical aspects and management of a retroperitoneal abscess]. AB - 14 patients with retroperitoneal abscess have been collected by the authors since June 1, 1988. The retroperitoneal abscess of multifactorial origin can be considered as a secondary disease. The physical clinical signs (e.g. psoas rigidity sign, palpable mass, costolumbal sensitivity) play central role in setting up of diagnosis, and these signs were present in more than 75% of the cases. The physical signs generally indicate advanced retroperitoneal abscess, and at the same time the contour of psoas muscle disappears and concavity of lumbal vertebras can be seen on plane abdominal X ray film. The exact diagnosis was achieved in mean 45 days after the on set of complaints, this fact urges, that the up-to-date imaging modalities (US, CT, NMR) should be applied earlier in septic conditions of unknown origin. Retroperitoneal surgical intervention was performed in their patients, in the future the percutaneous drainage procedure has to be considered as first intervention for retroperitoneal abscess. Retroperitoneal abscess secondary to malignant disease has unfavorable prognosis, 2 out of 14 patients with retroperitoneal abscess died, both of them had underlying malignancy. PMID- 1408068 TI - [The role of ultrasound in the indication for surgery in acute scrotum]. AB - Before the application of ultrasonography in the diagnosis of acute scrotum almost all cases were operated on, many unnecessarily. In the work presented here, we analyze surgical cases before and after the introduction of ultrasonography in our hospital. By the use of ultrasound, in the first year the number of operations and the number of non-justified operations were reduced to about the half and one fifth compared to corresponding data from earlier years. PMID- 1408069 TI - [Determination of the cerebrovascular reserve capacity by using acetazolamide as well as transcranial Doppler and SPECT tests]. AB - The aim of this study was the development of a simple bedside test to assess cerebrovascular reserve capacity using transcranial Doppler sonography. We tried to validate the increase in blood flow velocity as cerebrovascular reserve capacity in 20 (3 normal, 7 TIA, 10 completed stroke) patients. They were studied using transcranial Doppler sonography and rCBF SPECT before and after injection of 1 g acetazolamide. Their increases in blood flow velocity and changes in cerebral blood flow correlated significantly in the symptomatic hemispheres (p less than 0.001). Blood flow velocity between the two hemispheres (symptomatic and asymptomatic) was not significantly different at rest. We offer these simple and reliable methods in clinical studies to clarify the frequency of ischemic stroke of hemodynamic origin. PMID- 1408071 TI - [Professional competence]. PMID- 1408070 TI - [Percutaneous balloon-catheter dilatation of benign strictures of the bile ducts]. AB - Two cases of patients with benign biliary strictures (one with anastomotic and another with iatrogen stenosis of the common bile duct) successfully treated by percutaneous transhepatic balloon dilatation are presented. The patients have been symptom-free for 24 and 14 months, respectively. The author deals with the indication of the procedure including all the benign stenoses where surgical reconstruction is not feasible. It is also emphasized that the balloon dilatation needs rather long-time manipulation during which both the patient and the personnel are exposed to significant amount of scattered radiation. One of the important factors in decreasing the need for manipulation is the availability of adequate devices (a series of high pressure balloon catheters). PMID- 1408072 TI - [Health care education]. PMID- 1408073 TI - [Bipolarity of systemic dermatoses and its evolutional explanation]. PMID- 1408074 TI - [Experience with rectal application of Klion in man]. PMID- 1408076 TI - [Late results of intraoperative balloon dilatation in multilevel arterial diseases of the lower extremities]. AB - Since 1981, 93 intraoperative balloon dilatation have been performed in 78 patients suffering from occlusive arterial disease of the lower extremities. 42 iliac dilations were performed on 34 patients, where 8 patients required dilatations at two sites, and 26 patients only at one site (common iliac artery: 15, external iliac artery: 27). 44 patients received femoro-popliteal dilations of which 7 patients required dilations at two sites, and 37 patients only at one site for a total of 51 dilations. The follow-up period ranged from 1 to 60 months with an accumulated patency rate of 92% in iliac and 39.3% in femoro-popliteal segment at 5 years. Fourteen patients died by the fifth year after intervention. Most of these deaths were due to concurrent cardiac disease. By improving inflow or outflow and reducing operative stress in poor risk patients balloon angioplasty is a valuable adjunct to vascular reconstruction. PMID- 1408075 TI - [Correlations between radionuclide first passage, hemodynamic and respiratory function parameters in cor pulmonale patients]. AB - 37 patients with chronic cor pulmonale have been investigated with radionuclide first passage, microcatheter-technique, respiratory function investigation, furthermore blood gas analysis. Significant positive correlation have been found between the pulmonary circulation time and the pulmonary artery pressure; between the pulmonary mean transit time and the pulmonary artery pressure; furthermore between the pulmonary stagnation index was calculated for the characterization of peripheral pulmonary stagnation and the pulmonary artery pressure. Significant negative correlation have been found between the pulmonary circulation time, the pulmonary mean transit time and the vital capacity, the FEV1, furthermore the O2 saturation values. The authors establish, that on the base of the close correlations between the isotopic circulation parameters and the clinical data, the radionuclide first passage investigation is suitable for the demonstration of the current conditions of cardiopulmonary circulation. PMID- 1408077 TI - [Detection of delta F508 mutation in cystic fibrosis]. AB - The common major mutation (delta F508) resulting in the removal of a phenylalanine residue of the cystic fibrosis gene product has been identified in patients with cystic fibrosis in several European countries. The frequency of this mutation was analyzed in 39 Hungarian patients with cystic fibrosis and in some of their relatives. In 43 out of the total 65 persons involved in the study (66.15%), and in 50% of cystic fibrosis chromosomes the delta F508 mutation could be detected. 56.4% of the patients were homozygous for the mutation. The frequency of the delta F508 mutation in these Hungarian patients resembles the values found in Middle Europe. Pulmonary and enteral symptoms were more severe in cystic fibrosis patients with delta F508 mutation. Although the number of patients is relatively low, missing or mild lung involvement characterized the cases with non-delta F508 mutation. PMID- 1408078 TI - [Simultaneous occurrence of persistent hematuria (thin basement membrane nephropathy) and light-chain proteinuria (benign monoclonal gammopathy) in a middle-aged male]. AB - IgG lambda type of monoclonal gammopathy and thin basement membrane nephropathy were established in a middle-aged man examined because of persistent haematuria, lambda light-chain proteinuria and moderately diminished renal function. A 10% level of plasmocytosis was verified by bone-marrow aspiration. The more than 6 year follow-up showed the gammopathy to be benign. The thin basement membrane nephropathy was verified by electronmicroscopic analysis of renal tissue obtained by percutaneous renal biopsy: lamina densa of the glomerular capillaries thinned to 30-100 nm. In spite of the usually good outcome of thin basement membrane nephropathy, in this case it was accompanied by glomerular sclerosis, subsequent destruction of nephrons, hypertensive vascular alterations and a clinical deterioration of the renal function after 4 years. A rebiopsy excluded the possible complications (amyloidosis, non-amyloid immunoglobulin nephropathy, cylinder nephropathy, etc) of light-chain proteinuria. PMID- 1408079 TI - [Drug research in man: a new challenge in bioethics]. PMID- 1408080 TI - [In memoriam Sandor Lumniczer]. PMID- 1408081 TI - [Thr first successful gastric resection for peptic ulcer]. PMID- 1408082 TI - [Portrait of Prof. Penfield]. PMID- 1408084 TI - [Experience with hydrogen (H2) breath test]. AB - The authors applied regularly the hydrogen (H2) breath test during the medical investigations in patients with gastrointestinal symptoms. On the basis of the repeated examinations the hydrogen (H2) breath test is a sensitive, well repeatable method. After analysing of 108 examinations the authors have observed in 51.8% lactose intolerance, in 17.8% small intestinal bacterial overgrowth syndrome, in 46.4% motility disorders. The proportion of "low hydrogen producers" was 14.3%. Only 1/5 of patients with new diagnosed lactose intolerance had knowledge about the intolerance, and 10% was asymptomatic. In case of small intestinal bacterial overgrowth syndrome the repeated hydrogen (H2) test may indicate the effectivity of applied antibiotic therapy. The mean orocaecal transit time was 99 minutes and the normal range was 66-132 minutes, counted on the basis of mean +/- 2 SD. The authors suggest that the results support the important role of hydrogen (H2) breath test in the modern gastroenterological diagnostics. PMID- 1408083 TI - [Incidence of hepatitis B, C and D infection in chronic liver diseases]. AB - The authors tested hepatitis B (HBsAg, anti-HBs, anti-HBc, IgM anti-HBc, HBe, anti-HBe), C (anti-HCV) and D (anti-HD, IgM anti-HD) virus markers in the sera of 204 patients, who suffered from histologically confirmed chronic liver diseases (age: 18-72, average: 46.8 y) by Sorin Biomedica RIA and Abbott ELISA kits. On the basis of detailed virus serological tests, they obtained data indicating viral etiology in 62% of the cases. 33.3% of the patients were anti-HCV, 52.5% of the patients were HBV marker seropositive and 11.2% of the HBV seropositive cases were anti-HD seropositive. In 2% of the cases seropositivity of all the three viruses was proved. In 26% of the patients seropositivity of two viruses (HBV and HCV, or HBV and HDV) was proved. They observed severe, progressing liver diseases in patients with HBV, HCV and HDV marker seropositivity in a higher ratio than in seronegative patients. In the cases of combined virus marker seropositivity the incidence rate of chronic hepatitis and liver cirrhosis was higher than in only HBV marker seropositive patients, but did not differ significantly from those only anti-HCV seropositive. In the cases of fought-off HBV infection the severity of the liver disease was milder than in the cases of replication and integration stage. Anti-HD seropositivity occurred in all stages of HBV infection, but active HDV infection, in most of the cases, was observed only in cases in the integration stage. Anti-HCV seropositivity was observed mainly in the fought-off HBV infection stage. Their results suggest that HCV infection, like HDV infection, may suppress HBV replication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408085 TI - [The value of acetazolamide provocation combined with blood flow tests in the diagnosis of ischemic cerebrovascular diseases]. AB - In 28 (3 normal, 11 TIA, 14 completed stroke) patients 99mTc-HMPAO rCBF SPECT studies were performed at rest and after acetazolamide administration. For the investigations, a one-day protocol (the stress study directly followed the rest investigation) was used. The reconstructed and normalized slices were evaluated visually and semiquantitatively with a side difference analysis method. In the group of TIA patients, the abnormal results of the rCBF investigations increased from 55% to 82% after acetazolamide provocation. The corresponding results in the completed stroke group were 80% and 87%. After acetazolamide stimulation, hypoperfusion appeared or become more pronounced in the majority of the TIA group patients in contrast with the completed stroke patients with an unchanged or decreased perfusion abnormality. The semiquantitative evaluation method was mostly effective in the TIA group, where predominantly a one-sided cerebrovascular disorder was suspected. It was concluded that the 99mTc-HMPAO studies allow demonstration of the acetazolamide-induced cerebral perfusion alterations, and this method can be useful in the diagnosis and management of cerebrovascular disorders. PMID- 1408086 TI - [Wernicke encephalopathy in childhood osteosarcoma]. AB - Two children with osteosarcoma are presented in whom Wernicke encephalopathy with vomiting occurred during the chemotherapy. One of the children died with symptoms of toxic cardiomyopathy. Autopsy revealed Wernicke encephalopathy. The other child had similar symptoms (ocular signs, ataxia, somnolence). Parenteral thiamine had been given and after this therapy the child recovered from the encephalopathy. The authors emphasize the importance of the recognition of this neurological disorder occurring rarely in childhood: it can be cured with parenteral thiamine. Without thiamine treatment this condition is lethal. PMID- 1408087 TI - [Collective guilt and condemnation?]. PMID- 1408088 TI - [The place of pancreas transplantation in therapy]. AB - Insulin dependent diabetes mellitus is one of the most ravaging diseases of the civilised world mainly because of its secondary complications. Even the most careful exogenous insulin administration can neither maintain an entirely physiological glucose metabolism nor prevent the development of the late complications. Today pancreatic transplantation is the only therapy leading to total normalisation of glucose and lipid metabolism in type I diabetic patients. Beside the improvement of the life quality resulted by the independence of the insulin administration and of the dietary restrictions, secondary complications as nephropathy, retinopathy and neuropathy are positively influenced. Best results can be obtained with the simultaneous procedure, grafting kidney and pancreas from the same donor. In this case the grafted pancreas can also increase the patient survival rate and the kidney graft function rate comparing with the results of the kidney transplantation alone. In conclusion simultaneous pancreatic-kidney transplantation is clearly indicated for the treatment of type I diabetic patients with end-stage kidney disease. PMID- 1408090 TI - [Noninvasive imaging of the proximal coronary arteries by transesophageal echocardiography]. AB - Authors give an account of their experiences about the visualization of the proximal coronary arteries on the basis of the transesophageal echocardiographic examination of 45 patients. According to their observations the left main coronary artery, the bifurcation, the left anterior descending artery and the circumflex coronary artery were well visualized in 40 patients. With the help of pulsed Doppler-echocardiography the Doppler flow velocity spectrum of the coronary flow can be detected, which could be analysed in 25 patients. At the same time the visualization of the right coronary artery is less sensitive, valuable images could be detected only in 12 patients. The technique of the TEE visualization of the proximal coronary arteries is described. TEE seems to be a promising approach to the morphologic evaluation of the proximal coronary arteries and for functional pathophysiologic examinations of coronary blood-flow. PMID- 1408089 TI - [Urinary incontinence in pregnancy and puerperium]. AB - In a study of 421 patients questioned in immediate post-partum the author observed a urinary incontinence during pregnancy in 30.6% of the cases, this figure is comparable to those found in literature. The post-partum incontinence was not observed when forceps, vacuum extraction or caesarean section have been used. The urinary disorders observed during post-partum regresses spontaneously in 68% of the cases. However, one can ask the question on whether it is not reveal a light pelvic alteration which could cumulate at each delivery, so it would be necessary to use a pelvic training. PMID- 1408091 TI - [Examination of the orbit using a non-ophthalmologic ultrasound equipment]. AB - Ophthalmic examinations were performed for determining the suitability of seven different types of non-ophthalmic ultrasound equipments for ophthalmological purposes. According to the results, the instruments with probes of 5 MHz or higher frequency are appropriate for certain screening ophthalmological purposes in hospitals where ophthalmic ultrasound instrument is still missing. The possible indications are: approximate estimation of axial eye length for intraocular lens calculation, and visualization of gross intraocular and orbital diseases, such as retinal detachment, tumours, foreign bodies etc. In case of pathological result or in case of axial eye length different from the average value, the high resolution ophthalmological ultrasound examination is mandatory. The modern colour-coded Doppler ultrasound equipments were found suitable for the examination of the circulation of the eye and orbit. PMID- 1408092 TI - [Idiopathic thrombocytopenia caused by varicella]. AB - The authors deal with the case of a 6-year old girl in whom thrombocytopenia developed with haemorrhagic symptoms as a rare complication of varicella. They give a short review about the reasons and the etiology of idiopathic thrombocytopenic purpura, and deal with the mechanism of thrombocytopenia caused by varicella. PMID- 1408093 TI - [In memory of Tivadar Huzella]. PMID- 1408094 TI - [From the history of the management of leg ulcer]. PMID- 1408095 TI - [Addendum to the biography of Prof. Bossanyi]. PMID- 1408096 TI - [Theoretical possibility of using gene therapy in malignant diseases]. AB - The rapidly growing knowledge in molecular biology opened new methodological approaches, pharmacological targets, such as gene transfer or application of antisense oligomers. It is necessary to be familiar with the benefits and drawbacks of gene therapy to avoid the traps of unrealistic expectations and hopes, to solve moral and practical problems of gene manipulations and to find its proper values and rationals in the management of malignant tumors. PMID- 1408097 TI - [Late complications of pancreatic injuries following blunt abdominal trauma]. AB - In connection with three successfully operated cases authors are treating the types of late pancreatic complications after blunt abdominal trauma. It is emphasized that the preoperative diagnosis is difficult. Many times weeks or months pass away after the trauma without any symptoms and only developed complication can be noticed first. The importance of the first provision and the need for a careful examination of the pancreas at operation is underlined. In the case of the less suspicion of pancreatic injury they suggest wide, adequate drainage. At last they call attention to the responsibility of the surgeon making the first operation. PMID- 1408098 TI - [The thinning of the glomerular basal membrane in IgA glomerulonephritis]. AB - Ultrastructural changes of the glomerular basement membrane (GBM) in 34 patients with IgA nephritis and their possible correlation with the main clinical symptoms were examined. In 23 patients thinner than normal GBM segments were found with a mean thickness of 116-120 nm (measured by the method of Osawa). Often foot process fusion but neither disruption nor deposition of immune complexes was seen in the affected capillaries. All patients had hematuria, while those with thin GBM segments had more severe hematuria and more episodes of macrohematuria. Other clinical features were unrelated to ultrastructural changes. It is suggested that the thin GBM may be a predisposing factor to hematuria. PMID- 1408099 TI - [A case of adult Gaucher disease]. AB - The authors describe a case of an adult patient having Gaucher's disease, who had hepatosplenomegaly and pancytopenia. The diagnosis was established by the low level of leukocyte beta-glucosidase and by histology of bone marrow, liver and spleen. The patient had no bone pain, but MRI described characteristic lesions of the femur. Serum acid phosphatase was characteristically elevated. The hypersplenism was reduced after splenectomy. The patient has a daughter with central nervous system dysfunction. Her chromosome examination is normal, but she has lower leukocyte beta-glucosidase activity too. She may have a Gaucher's disease of type II, the acute neuropathic form. PMID- 1408100 TI - [Therapeutic possibilities in biliary lithiasis]. PMID- 1408101 TI - [Ethical "indication" for medical decisions to be made at the end of life]. PMID- 1408102 TI - [Prognostic value of cell proliferation markers in malignant tumor diseases]. AB - Novel methods used in studying the proliferation activity and cell kinetics of malignant neoplasms such as: the in vivo and in vitro bromodeoxyuridine labeling, the flow cytometric DNS analysis, the immunohistochemical demonstration of the so called proliferation associated antigens and the counting of nucleolar organized regions are briefly introduced. The data obtainable by these methods are reviewed and critically discussed. The prognostic value of the obtained data and their utility in planning and monitoring of cancer patients' therapy are also discussed. PMID- 1408103 TI - [Significant bacteriospermia. Value and limits of sperm count in andrology]. AB - The data concerning bacteriospermia--are very different in the literature. Asymptomatic andrologic patients, and as control group--patients of the outpatient department for male adnexitis--were studied. Cultivation of aerobic bacteria and mycoplasmas has been recently accomplished by quantitative bacteriological analysis and chlamydia diagnostic. The microbiological screening of 210 andrologic patients ejaculate has given the following results: 19.6% were sterile, 21.0% were colonised by apathogens, 59.1% were positive: 6.2% Mycoplasma hominis, 15.8% Ureaplasma urealyticum, 13.3% Chlamydia trachomatis, 51.9% other aerobic pathogens. 27.6% of samples contained more then one kind of bacteria strains. Quantitative isolation of aerobics and mycoplasmas in both andrological and male adnexitis patients groups showed the following distribution. In the andrologic groups 14.7% of samples contained 10(4) CFU/ml, 9.6% more than 10(4) CFU/ml aerobic bacteria; in the male adnexitis group nearly twice higher values could be observed (20.2% and 19.5%). The distribution of mycoplasma CFU/ml was the following; andrologie group: 20.1% of samples contained 10(4) mycoplasma CFU/ml, 37.5% more than 10(4) CFU/ml; in the male adnixitis group the identical values: 22.9%, 66.9%. Chi 2 statistical analysis showed significant difference ((p = 0.000) in the distribution of data in the two groups. On the other hand both of the groups contained all kinds of bacteriological concentration and even negative cases. Therefore authors suggest more biochemical investigations for detecting inflammatory diseases. Spermaparameters (motility and progressive motility) of andrological patients, divided by sperm concentration (cell number above and under 20 million/ml) and the degree of infection (non infected, slightly infected, and above 10(4) CFU/ml) were significantly different in the seriously infected group by variance analysis (p = 0.000). PMID- 1408104 TI - [Experience with using a myocutaneous flap, obtained from the gluteus maximus, in covering sacral decubitus wounds]. AB - Nonsurgical treatment of pressure sores of the sacral region showed in long term poor results. After a short review of surgical procedures the method of gluteus maximus myocutaneous flaps is described. The results suggest that the method offers a well vascularised and resistant soft tissue cover of the pressure sore and it can be performed in any surgical department. Stay in hospital may decrease significantly and the hope for a complete rehabilitation increases. PMID- 1408105 TI - [Cobalt-induced asthma in workers exposed to hard metal dust]. AB - A case of 39 years old woman with asthma bronchiale associated with cobalt exposure is reported. Specific bronchial provocation tests in these patients supported the diagnosis of hard-metal-induced asthma and implicated cobalt as the agent responsible. The relevant literature data are reviewed. PMID- 1408106 TI - [The question of managing the placental stage of delivery]. PMID- 1408107 TI - [The nurse as an aide for the (male) physician]. PMID- 1408108 TI - [Simply thinking about it]. PMID- 1408109 TI - [Nursing in the operating room]. PMID- 1408110 TI - [We were in Switzerland]. PMID- 1408111 TI - [Farewell thoughts--did we reach our goal? A reflection on our period of training]. PMID- 1408112 TI - [Noted in short]. PMID- 1408113 TI - [Much noise about ... chambers?]. PMID- 1408114 TI - [Shoulder arthroscopy in degenerative and inflammatory diseases]. AB - A new concept of shoulder arthroscopy is presented based on experience with 800 shoulder arthroscopies. All open surgical procedure on the shoulder are preceded by arthroscopy. The procedure is performed with the patient lying on his or her side. The medium is CO2, and the advantages are less bleeding, a natural picture, no fluid edema. After diagnostic arthroscopy (with CO2), operative arthroscopy (with fluid) or open joint surgery follows. The surgery can easily be performed in the same position for good access with any approach. Preliminary diagnostic arthroscopy helps to plan the procedure (approach, additional surgery). Minimal exposure is beneficial for faster rehabilitation. PMID- 1408115 TI - [Arthroscopy of the wrist and elbow joint]. AB - Arthroscopy of the wrist and elbow is a helpful diagnostic procedure in patients with chronic disability not demonstrated by clinical and radiological examinations. At the wrist, especially triangular fibrocartilage, chondral or ligamentous defects can often not be demonstrated by other tests. Arthroscopy of the wrist allows examination of more than a dozen separate articular surfaces and the function of eight discrete joints. The geometry of the elbow joint limits intra-articular inspection and the use of instruments. The risk of neurovascular injuries is great and depends on exact puncture sites and portals. Its efficiacy is not yet proven. PMID- 1408116 TI - [Current status of diagnostic and surgical hip arthroscopy]. AB - Due to the anatomy and topography of the hip, clinical diagnostic procedures are often not very significant. Even the use of highly technical examination methods mostly does not allow differentiation of specific hip problems and do not give exact information about the extent and stage of the lesion. This applies specifically for rheumatoid diseases. Arthroscopy of the hip joint, like other big joints of the extremities, closes this diagnostic gap. Directly visualized findings on the joint, in addition to the results of joint aspiration and histological biopsies, give one security in finding the right diagnosis and planning adequate therapy. The conventional surgical approach to the hip joint leads to large wounds and to corresponding risks and damage to the patient. The advantages of arthroscopy are obvious. It was shown that arthroscopic surgery can be used very efficiently in cases with loose-body, osteochondrosis dissecans, scattered cartilage fragments, or septic arthritis. The other therapeutic application is in cases with rheumatoid arthritis where an arthroscopically assisted synovectomy to the hip achieves a high rate of success without temporary luxation. Diagnostic arthroscopy and arthroscopic surgery to the hip have been used in the Orthopedic Department of the University of Ulm since autumn of 1984. The possibilities and limitations of this surgical procedure have been evaluated in more than 100 cases. Based on our experience with arthroscopy on hip joints, we think that this procedure is very helpful for making a diagnosis and administering therapy. PMID- 1408118 TI - [Endoscopy of the spine: minimally invasive therapy]. AB - Since 1982 discoscopy has proved its value as a mean of continuous optic control of percutaneous intradiscal procedures. Thus, precisely oriented removal of disc tissue became possible for posterior decompression. Since 1989, discoscopy has opened the way for optically controlled intradiscal laser application. Besides decompressive procedures, since 1988 specific elaboration of the vertebral plates for percutaneous interbody fusion has also become available under discoscopic control. A most promising prospect is the technique of foraminoscopy introduced in 1991, which also opened the way to extradiscal exploration. The further development of versatile fine working scopes will be a bigger and bigger challenge to conventional techniques, as the concept of minimal intervention in spine surgery becomes more and more complete. PMID- 1408117 TI - [Diagnostic arthroscopy and arthroscopic surgery of the upper ankle joint]. AB - Arthroscopy of the ankle joint was limited to the anterior compartments for a long time. The key to the entire diagnostic and therapeutic arthroscopy procedure on the ankle joint was the distension of the joint space through modern distraction techniques. The distraction devices available make arthroscopic surgery of the ankle joint as effective as in other joints like the knee and shoulder. Distension of the joint space allows visualization of all compartments, including the posterior ankle. In the case of hidden cartilage pathology of the posterior talus, an osteotomy linked with hardware removal through a second operation can be avoided today. The indications for arthroscopy of the ankle are pain, swelling, instability, hemarthrosis and joint locking. Generally, arthroscopy of the ankle joint is performed utilizing three general portals: anterolateral, anteromedial and posterolateral. Arthroscopic standard equipment, including the small joint set, is sufficient to treat the major part of ankle pathology through the standard portals. Arthroscopic ankle joint debridement in degenerative arthritis, removal of osteophytes, elimination of loose bodies and the management of soft tissue and bony impingement are possible. A complete synovectomy can be performed, including the posterior compartments. The treatment of osteochondritis dissecans is facilitated through the transmalleolar approach in combination with the distraction device. Arthroscopic ankle arthrodesis is possible and induces less trauma because an arthrotomy can be avoided. In our opinion diagnostic arthroscopy and arthroscopic surgery of the ankle joint is a procedure of great benefit for the patients if the indications are strictly adherred to. PMID- 1408119 TI - [Use of lasers in arthroscopy]. AB - Arthroscopic surgery has become a routine procedure, thanks to the availability of excellent video systems and the development of new and efficient instruments. Since early 1980 several groups have been developing arthroscopic laser surgery. Laser technology is ideal for use in endoscopic surgery because lasers are potentially extremely small but nevertheless powerful tools with many advantages. Initially, attempts were made to modify CO2 lasers an Nd: YAG lasers for arthroscopic surgery, since these devices were readily available in many hospitals, but they proved unsuitable for arthroscopy. Clear definition of the desired goals and much experimentation eventually led to the development of three suitable systems: excimer, holmium: YAG and erbium: YAG lasers. After extensive investigation in the past few years, many groups have, for technical reasons, now opted for the holmium: YAG-laser as the best compromise. Lasers are used in arthroscopy not only to divide tissue but also to smoothen cartilage, for hemostasis, for percutaneous lumbar and cervical disc surgery, for photodynamic therapy, for tumor therapy and in diagnosis. The threshold to clinical practice in orthopedic laser surgery has now been crossed. Lasers must now show, in prospective clinical studies, that their theoretical advantages are matched in practice. PMID- 1408120 TI - [Spastic paralysis: orthopedic treatment strategies]. PMID- 1408121 TI - [Development of orthopedic treatment of cerebral palsy]. PMID- 1408122 TI - [Treatment of deformities of the locomotor system in hemiplegia]. AB - In spastic hemiplegia mainly one side of the body is affected. In both the upper and the lower extremity the distal parts (hand and foot) are more severely involved than the proximal region. In cases of minor involvement the goal of treatment in the upper extremity is to achieve functional improvement by means of splinting and surgery. In cases of severe alterations cosmetic improvement without much functional gain is all that can be expected. Gait analysis has demonstrated that there are four basic patterns that can be related to the severity of involvement. In type I muscle imbalance exists without a contracture. In type II there is contracture of the muscles of the posterior compartment of the calf. In type III, in addition to the changes around the ankle joint, contractures around the knee are present, and in type IV also hip problems. Functional improvement can be achieved by means of splinting and surgery in all types. Basic principles of treatment have developed as a result of the application of gait analysis and dynamic electromyography. Specific examples of such treatment principles have recently been presented by Gage. PMID- 1408123 TI - [Surgical treatment concepts of deformities of the upper extremities in infantile cerebral palsy]. AB - To correct the most frequent deformity of the spastic hand, muscle release and transfer operations, such as distal slide of hand and finger flexors (according to Scaglietti and Gob), release of the adductor pollicis and flexor pollicis brevis muscle (Matev), and transposition of the flexor carpi ulnaris muscle to the dorsal aspect of the hand, should be performed. These basic operations on the spastic hand can be supplemented by release or transposition of additional muscles of the fingers or hand. Bony procedures should be done to stabilize and augment the grip between thumb and second finger. In selected cases arthrodesis of the wrist can be performed to stabilize the hand in a functional position. The outcome of operations on the spastic hand depends on the application of correct indications as well as on postoperative physiotherapy. A slight functional gain, or even a purely cosmetic improvement, may mean a lot to the patient. In respect of professional rehabilitation of adolescents, operative correction of a deformed hand can help to improve manual skills and thereby increase job chances. PMID- 1408124 TI - [Spinal disorders in cerebral palsy--surgical procedure]. AB - The incidence of scoliosis in cerebral palsy is related to the severity of the neurological involvement, being most prevalent in patients with spastic quadriplegia. Neuromuscular spinal deformity, when present, may progress after cessation of skeletal growth, and the success of orthotic treatment for scoliosis is unpredictable. Hip pathology is directly related to pelvic obliquity but has no causal relationship to the development of scoliosis. Adequate preoperative nutritional assessment is vital to reduce perioperative complications, and segmental spinal fixation is the instrumentation of choice. Anterior arthrodesis is indicated for rigid deformities and for those thoracolumbar and lumbar curves extending into the pelvis with pelvic obliquity and spinal decompensation. PMID- 1408125 TI - [The hip in infantile cerebral palsy, natural developmental course and treatment concepts]. AB - Classification of cerebral palsy according to the topographical distribution of clinical phenomena permits determination of a prognosis of the natural history of CP and the probability of hip problems to some extent. In 55 patients with CP, 101 muscle release operations were performed between 1971 and 1988. Preoperatively, the diagnosis was established by the neuropediatrician, function was evaluated according to the Rancho-los-amigos system, and the X-rays of the hip were assessed according to Reimers. For the postoperative evaluation patients were grouped according to neurologic diagnosis: hemiplegia (4), diplegia (19), total body involvement (31). Patients with hemiplegia had no functional or radiological changes as a result of the operation. In diplegia functional deterioration was seen in 4 cases (21%); in 3 cases (16%) this meant loss of the ability to walk. The migration percentage was improved from 48% to 39% on average. In 19 cerebral palsy patients with total body involvement surgery was considered to be indicated on the basis of a suspected dislocation of the hip. No functional changes occurred as a result of surgery. Hip dislocation was successfully prevented in 90% of the cases. The migration percentage was improved from 73% to 33%. In another 12 patients with total body involvement, adductor and iliopsoas release was performed to allow better hygiene and care and for pain relief. These goals were achieved; neither the Rancho-Los-Amigos function classification system nor X-rays were used to evaluate the results. PMID- 1408127 TI - [Treatment of spastic club foot]. AB - In 38 patients with spastic cerebral palsy, treatment was carried out for talipes equinovarus. There were 12 children with spastic hemiplegia, while 24 had diplegia or tetraplegia. Surgery was done with the goal of achieving plantigrade and muscle-balanced feet. In 24 feet of 19 children tibialis anterior transfer was performed, while tibialis posterior transfer was done in 20 feet of 19 patients. Without exception, additional surgery was performed on the triceps surae (30 x ATLs and 16 Vulpius operations); medial arthrolysis was also necessary in 6 cases. The clinical results were assessed by the senior author in the weekly neuro-orthopedic clinic an average of 3.2 years after surgery. An additional questionnaire was sent to all patients' families asking for their subjective assessment of the surgery performed. Figures were collected for 30 patients with 38 treated feet. The results were evaluated according to Kling's criteria. We saw good and very good results in 75% of the patients (4 feet very good, 23 feet good), while 25% of the patients (9 feet in 7 patients) showed poor results with over-corrections and calcaneo-valgus foot as the main problem. The best results were seen in spastic hemiplegia and the poorest in patients with severe tetraplegia and total body involvement. PMID- 1408126 TI - [Treatment concepts in knee malposition within the scope of primary neurologic diseases]. AB - Disease and trauma to the central and peripheral nervous system can result in various disturbances to the stability and mobility of the knee joint. The aims of orthopaedic treatment in flaccid paralysis, spasticity, rigidity, athetosis and ataxia are discussed. The effect on the musculo-skeletal system is most severe when the damage occurs prenatally. The tendency to deformity in perinatal cerebral spastic disorders of movement can be considerably reduced by early systematic functional treatment. Active and passive exercise, corrective and reflex inhibiting casts and orthoses have proved their value in the prevention and treatment of muscle contractures in flaccid paralysis and spasticity. The dangers of treatment, such as subluxation of the knee and hip joint, osteoporotic fractures, and traction paralysis, must be taken into account. Muscle contractures often hinder function, both in spasticity and in flaccid paralysis, more than the underlying disease. The operative treatment of flexion contractures and impaired knee flexion in the swing phase of the step is discussed. Gait analysis facilitates the planning of treatment. The hip, knee and ankle joints must be treated as a single functional unit. PMID- 1408128 TI - [Treatment concepts of tertiary damage of the locomotor system after craniocerebral trauma]. AB - Brain injuries are the most frequent cause of handicap in young adults. The success of rehabilitation depends mainly on the avoidance of tertiary lesions of the locomotor system. Between January 1989 and December 1991, 54 patients were treated at the neuro-rehabilitation unit of the Neurology Department of the University Hospital for severe brain injuries. On admission these patients were in different stages of recovery. All patients underwent physiotherapy adapted to their specific needs. The decision as to whether other kinds of treatment were indicated depended on the patients' problems in the recovery phase reached and on the presence or absence of tertiary lesions. In 14 patients, contractures caused by spasticity were successfully treated with plaster casts, which were changed weekly. These contractures were corrected sufficiently. In 5 other patients contractures, also caused by spasticity, were treated with regional anaesthesia administered through an implanted catheter system. In 11 patients a system for continuous intrathecal administration of Baclofen was implanted. Central side effects could be avoided while a lasting decrease of spasticity and hyper reflexia was achieved. Persisting tertiary lesions, such as contractures, dislocations and spinal deformities, were corrected surgically. PMID- 1408130 TI - [Pain therapy with Toratex. Official satellite symposium of the Xth World Congress of Anesthesiology. The Haague, 15 June 1992]. PMID- 1408129 TI - [Peri-articular calcinosis after craniocerebral trauma--the natural course and treatment concepts]. AB - Occurrence of periarticular ossification (PAO) is a serious complication in the rehabilitation of patients with neurological diseases, especially those with severe head injuries. The present concept for operative intervention in PAO postulates late surgical treatment after "maturation" of these heterotopic ossifications, because of a suspected higher rate of reoccurrence after early removal. In a retrospective analysis of nine arthrolysis in six patients with neurological diseases suffering from PAO (five patients with traumatic apallic syndrome and one patient with spontaneous subarachnoidal haemorrhage), the validity of a new concept of treatment of primary neurological diseases was investigated. Because of the well-known secondary and tertiary problems (fibrotic stiffness, osteoporosis, compression syndrome of peripheral nerves, muscle atrophy), we chose early removal of the ossifications. Our results demonstrate that the former concept of surgical intervention in "mature PAO" only can no longer be recommended as superior to early surgical treatment in neurological diseases, particularly in patients with traumatic apallic syndrome associated with PAO. PMID- 1408131 TI - Association of Fyn with the activated platelet-derived growth factor receptor: requirements for binding and phosphorylation. AB - Three members of the Src family of tyrosine kinases [pp60c-src (Src), p59fyn (Fyn) and pp62c-yes (Yes)] are ubiquitously expressed, and are thus likely to have general roles in growth control. We have previously shown that, after addition of platelet-derived growth factor (PDGF) to quiescent cells, all three kinases become activated and associated with the PDGF receptor. We have now addressed the requirements for this association. First, we have used a baculovirus expression system to show that Fyn associates with the activated PDGF receptor in vitro in the absence of other proteins, demonstrating that the association between the two molecules is direct. Second, by generating cell lines expressing chimeric molecules consisting of Fyn sequences fused to a portion of beta-galactosidase, we found that the SH2 domain of Fyn is necessary for ligand stimulated association with the PDGF receptor in vivo. Third, those fusion proteins that associated with the PDGF receptor also became phosphorylated in vivo following PDGF treatment, and in in vitro kinase assays, suggesting that the amino-terminal half of Fyn contains the sites of PDGF-stimulated phosphorylation. Partially purified, kinase-negative Fyn also became phosphorylated in the activated PDGF receptor complex in vitro, demonstrating that the PDGF receptor phosphorylates Fyn, rather than the novel phosphorylations occurring by autophosphorylation. PMID- 1408132 TI - The v-ski oncogene cooperates with the v-sea oncogene in erythroid transformation by blocking erythroid differentiation. AB - The avian retrovirus oncogene v-ski was analysed for its ability to alter the differentiation program of erythroid cells and to cooperate with tyrosine kinase oncogenes in leukemogenesis. For this, a retrovirus combining v-ski with a temperature-sensitive version of the v-sea oncogene was constructed. In transformed erythroblasts, v-ski disturbed the concerted expression of several erythrocyte genes, leading to an abnormal erythroblast phenotype. Expression levels of hemoglobin and erythrocyte anion transporter (band 3) were elevated, while expression of the erythroid-specific histone H5 was strongly suppressed. v ski could also be shown to repress or severely retard the temperature-induced erythroid differentiation of v-ski/ts-v-sea-transformed cells. The undifferentiated cells had an abnormal erythroblast or early reticulocyte phenotype characterized by unusually low levels of histone H5. In chicks, the v ski/ts-v-sea virus displayed enhanced leukemogenicity compared with viruses containing just the single oncogenes. Thus, v-ski cooperates with tyrosine kinase oncogenes in a similar fashion to the v-erbA oncogene, however the pattern of genes affected by these two oncogenes is different. PMID- 1408133 TI - Specific and complex interactions of murine p53 with DNA. AB - Biologically active mutant p53 from Balb/c mouse tumor cells (Meth A) was analysed for its specific interaction with DNA. Restricted phage lambda DNA, representing DNA of high complexity with regard to sequence and secondary structure, was used to probe for such an activity in a target-bound DNA-binding assay, using doubly immunopurified p53. A single lambda DNA fragment was specifically retained with very high affinity (KD = 10(-10) M). Specific DNA binding was shown to be an intrinsic property of p53, as it could be blocked with p53-specific monoclonal antibodies PAb122 and PAb421. The characteristics of the DNA binding of p53 to this lambda DNA fragment, as well as the structural properties of this fragment, suggested the possibility that p53 might be able to interact with nuclear matrix attachment region (MAR) DNA. Indeed, established genomic MAR elements were specifically bound by Meth A p53, whereas no binding was observed to an AT-rich control DNA. The interaction of p53 with MAR elements in vitro is compatible with the idea that p53 in vivo is involved in the regulation of replication and/or expression of cellular DNA. Complex DNA interactions were not restricted to mutant p53 from Meth A cells. Mutant p53 of a different conformational phenotype (PAb246+ 'wild-type' as opposed to PAb246- 'mutant' for p53 from Meth A cells) from minimally transformed T3T3 cells, as well as genotypic wild-type p53 expressed by a recombinant baculovirus in insect cells, exhibited similar DNA-binding properties. PMID- 1408134 TI - Analysis of temperature-sensitive functions of Fos: lack of a correlation between transformation and TRE-dependent trans-activation. AB - We have identified and characterized a mutant v-Fos protein (DN16G) that is temperature sensitive for transformation. This protein contains an asparagine to glycine substitution at position 156 in the basic region encompassing the DNA contact site. This point mutation also strongly decreases trans-activation in a transient expression assay, using the collagenase 12-O-tetradecanoyl phorbol 13 acetate (TPA)-responsive element (TRE) as the target element. However, the apparent correlation between trans-activation and transformation does not hold in view of the observation that under certain temperature conditions (DN16G at 39.5 degrees C and E300 at 37 degrees C) both proteins showed similarly poor transactivation properties, but dramatically differed in their transforming potential. These findings clearly suggest that the activation of transcription via TREs as analysed in this study is not a crucial mechanism in Fos-induced transformation. PMID- 1408135 TI - Cloning and developmental expression in Xenopus laevis of seven additional members of the Wnt family. AB - Degenerate oligonucleotide primers encoding highly conserved regions of Wnt related proteins were used with the polymerase chain reaction (PCR) to amplify cDNA derived from Xenopus laevis embryos. cDNA sequences partially encoding seven additional members of the Xwnt gene family were isolated using this strategy. These cDNAs have been given the designation Xwnt-2, Xwnt-6, Xwnt-7A, Xwnt-7B, Xwnt-7C, Xwnt-8B and Xwnt-10 based on their amino acid identity with previously described Wnts. With regard to the timing of expression of these Xwnts during embryonic development, Xwnt-2, the least abundant transcript, was first detected during the neurula stage, while Xwnt-8B transcripts were first detected at the gastrula stage, and decreased by the tailbud stage. Multiple transcripts of Xwnt 6 were detected at varied times during development beginning at the gastrula stage. In contrast, Xwnt-7A, -7B and -10 transcripts were not detected until the tailbud stage. With regard to expression in adult tissues, Xwnt-6, -7A, -7B, -8B and -10 were all expressed abundantly in the brain, and to a lesser extent in a variety of other tissues. Whole-mount in situ hybridization was then employed to monitor the spatial expression of selected Xwnts. Xwnt-7A and -10 transcripts were detected in distinct areas of the developing brain of tailbud-stage embryos. The temporal and spatial differences in expression suggest different roles for these new Xwnt family members in Xenopus development. PMID- 1408136 TI - Functional analysis of the SH2 and SH3 domains of the lck tyrosine protein kinase. AB - p56lck is a lymphoid cell-specific member of the src family of cytoplasmic tyrosine kinases. In helper and cytotoxic T cells it is physically associated with the CD4 and CD8 surface antigens and appears to play a role in signal transduction during T-cell activation. p56lck contains both an SH3 and an SH2 Src homology domain. Such domains have been suggested to play a role in the regulation of the activity or function of both receptor and non-receptor tyrosine protein kinases. Deletion of either or both domains in p56lck was found here to activate the protein and to lead to increased phosphorylation of the autophosphorylation site, Tyr-394, in vivo. These findings are consistent with the hypothesis that these domains participate in repression of the kinase activity of p56lck. None of the deleted forms was capable of transformation of fibroblasts. Deletion of the SH3 domain of a constitutively activated form of p56lck, p56lckF505, did not diminish the transforming activity of this protein. This suggests that this domain is dispensable for the transformation of fibroblasts by p56lck. In contrast, deletion of the SH2 domain abolished the transforming potential of activated p56lckF505. However, interpretation of this effect is made somewhat difficult because the mutation also lowered the steady state abundance of the protein. PMID- 1408137 TI - Promoter region of the murine fibroblast growth factor receptor 2 (bek/KGFR) gene. AB - Fibroblast growth factors (FGFs) and their receptors play an important role in cell growth, angiogenesis and embryonal development. Four distinct genes encoding fibroblast growth factor receptors (FGFRs) were identified: flg, encoding FGFR1, bek encoding FGFR2, and the genes for FGFR3 and FGFR4. Both FGFR2 and keratinocyte growth factor receptor (KGFR) are encoded by the same gene, bek. To study the regulation of expression of the FGF receptors we analysed the DNA sequence flanking the 5' region of the cDNA of murine FGFR2 to seek elements that control its transcription. A 5-kbp fragment containing the 5' end of the cDNA was isolated from mouse genomic library and used to map the promoter region. We found that the sequence encoding the 5' non-translated region of the FGFR2/KGFR cDNA contains an intron located 210 bp upstream from the translation start site. Using RNAase protection and primer extension, we identified the mRNA start 37 bp upstream from the beginning of the bek cDNA. The promoter activity was found to reside in a 1.3-kbp fragment upstream from the cDNA, and deletion mapping further localized the promoter to a 0.7-kbp fragment. The sequence of this region shows high G+C content (62%), which is particularly emphasized in the 200 bp upstream from the mRNA start (80% G+C). This region contains the CCGCCC, GGGCGG AND GGAGG motifs also found in promoters of other growth factor receptors. Neither TATA nor CAAT boxes were found near the RNA start site. The characterization of this promoter will allow studies of the regulation of expression of the FGFR2 during development and in pathophysiological states. The differences between the promoter sequence of the gene for FGFR2 (bek) and FGFR1 (flg) may explain their differential expression during development. PMID- 1408138 TI - Mast cells sensitive to v-H-ras transformation are hyperinducible for interleukin 3 expression and have lost tumor-suppressor activity. AB - Subcloning of interleukin 3 (IL-3)-dependent PB-3c mastocyte cells revealed two populations, of which only one is sensitive to oncogenic transformation by v-H ras. The corresponding tumors produce IL-3 and grow in vitro in the absence of exogenous IL-3 [Nair, A.P.K., Diamantis, I.D., Conscience, J.F., Kindler, V., Hofer, P. & Moroni, Ch. (1989). Mol. Cell. Biol., 9, 1183-1190]. In the present investigation, IL-3 gene regulation was compared in ras transformable (rT) and ras nontransformable (rNT) lines. We report that upon expression of v-H-ras rT clones but not rNT clones express low levels of IL-3 mRNA as detected by reverse polymerase chain reaction. Treatment with ionomycin, a calcium ionophore, induced high levels of IL-3 expression only in ras-expressing rT clones. Somatic cell fusion between the rNT clone 20 and the IL-3-expressing mastocytoma line V2D1 led to down-regulation of IL-3 expression and to the requirement for exogenous IL-3 for in vitro growth and tumor suppression. In contrast, rT clone 15 lacked tumor suppressor activity and failed to down-regulate IL-3 expression in somatic hybrids which grew in vitro without added IL-3. Our results indicate that IL-3 gene expression is a critical determinant for the generation of v-H-ras-induced mast cell tumors and show that disturbances in IL-3 gene regulation can be detected already at the premalignant level in v-H-ras transformation-sensitive cells. PMID- 1408139 TI - p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus. AB - Bronchial epithelial dysplasia is believed to precede invasive squamous cell carcinoma of the lung. Six paired dysplasia and tumour samples were distinguished histologically in sections of formalin-fixed paraffin-embedded lung tissue from patients with lung cancer. Additionally, samples of dysplastic bronchial epithelium were obtained from patients without lung tumours. Microdissection of the unstained sections provided dysplastic and tumour samples from which DNA was prepared for comparison with the patients' constitutional genotype, using polymerase chain reaction-based restriction fragment length polymorphism analysis. All six samples of tumour and the paired adjacent samples of bronchial dysplasia showed loss of heterozygosity (LOH) at loci on the short arm of chromosome 3. Five of the six cases showed involvement of the p53 gene as assessed by LOH at the AccII site within the gene, and by immunoreactivity to CM 1, an antibody which recognizes the mutated form of the p53 protein in paraffin embedded material. Of the dysplastic samples, obtained from patients without invasive tumours, all three showed LOH at 3p; one sample showed LOH at the AccII polymorphic locus within the p53 gene, and another sample, uninformative at this locus, stained positively with this antibody. These results indicate that somatic genetic changes are present in preinvasive lesions in the bronchus. PMID- 1408140 TI - The c-myb proto-oncogene product binds to but does not activate the promoter of the DNA polymerase alpha gene. AB - The myb proto oncogene product (c-Myb) is a transcriptional regulator and its expression and function are tightly linked to the cellular entry into S phase and DNA synthesis. It has been shown [Venturelli, D., Travali, S. & Calabretta, B. (1990). Proc. Natl. Acad. Sci. USA, 87, 5963-5967] that inhibition of T-cell proliferation by a myb antisense oligomer is accompanied by down-regulation of DNA polymerase alpha expression. To examine whether the transcription of the DNA polymerase alpha gene is directly regulated by c-Myb, we have identified and characterized the 5' regulatory region of the human DNA polymerase alpha gene. Two major and several minor transcription start sites were identified by nuclease S1 mapping. DNA sequence analysis showed that the promoter region contains no TATA box, one CCAAT box and putative Ap-1, AP-2 and E2F binding sites. In DNAase I footprinting, the bacterially expressed c-Myb protected six sites in the 5' flanking region of the human DNA polymerase alpha gene. However, c-Myb did not activate the DNA polymerase alpha gene promoter in a co-transfection assay. Our results suggest that an unknown factor(s) is required for the c-Myb-induced activation of the DNA polymerase alpha gene promoter, or c-Myb does not directly activate this promoter. PMID- 1408141 TI - First non-vertebrate member of the myc gene family is seasonally expressed in an invertebrate testis. AB - We have cloned and characterized the first non-vertebrate member of the myc gene family, pAv-myc, from testes of the Northern sea star, Asterias vulgaris (Echinodermata). We have used an oligonucleotide that is complementary to the virtually 100% conserved vertebrate c-myc box A in the second exon and a cDNA library constructed from spermatogenically active testes. Relatives of this echinoderm existed approximately 100 million years prior to the origin of the earliest known organism for which c-myc sequence is currently available (the trout). Nonetheless, our cDNA encodes a protein with approximately 30% amino acid identity and 46% overall conservation to human c-myc. Regions of substantially higher conservation (63-95%) correspond in order to the transcriptional activation (boxes A, B and C), casein kinase II phosphorylation, nuclear targeting, basic DNA-binding and oligomerization domains in the second and third exons of human c-myc. Sea star c-myc cDNA detects a 2.7-kb transcript on Northern blots of monthly samples of testicular tissue from field-collected individuals (n = 6-8), indicating peak expression during active spermatogenesis. This is also the first example of seasonal variation in expression of c-myc during spermatogenesis in laboratory or natural populations of any animal. It is intriguing to speculate about the potential oncogenic character of c-myc in this invertebrate, in which tumors have not yet been observed, and about the possibility that c-myc is more widely present in eucaryotes than has been anticipated. PMID- 1408142 TI - Suppression of tumorigenesis by the breast cancer cell line MCF-7 following transfer of a normal human chromosome 11. AB - Breast cancer development is associated with several genetic abnormalities. Loss of heterozygosity in the short arm of chromosome 11 has been observed in 30% of tumors. We found homozygosity at five chromosome 11 polymorphic loci in genomic DNA of the MCF-7 breast carcinoma cell line, suggesting a possible loss of one chromosome 11. We have studied the transformed and tumorigenic phenotypes of MCF 7 cells following introduction of a normal human chromosome 11 via microcell fusion. MCF-7/H11 cell hybrids, containing chromosome 11, showed in vitro characteristics similar to the parental cell line. However, tumorigenicity in athymic mice was completely suppressed. Since tumor formation by MCF-7 cells is estrogen dependent, we have analysed the expression of the estrogen receptor and of the estrogen-activated gene pS2. No difference was detected between the parental MCF-7 cells and the derived chromosome 11 cell hybrids, indicating that the mechanism of MCF-7 tumor suppression by chromosome 11-associated functions does not directly involve the estrogen/estrogen receptor molecular pathway. PMID- 1408143 TI - Characterization of an angiosarcoma-inducing mutation in the erbB oncogene. AB - The erbB oncogenes of two transducing viruses that arose in chicken 5005 have been molecularly characterized. One of these viruses, AEV-5005, caused erythroblastosis. The other, AAV-5005, caused angiosarcoma. Both viruses had identical 5' junctions of viral and host sequences, indicating that both arose from the same proviral insertion. The erbB oncogenes of both viruses encoded transmembrane, kinase and C-terminal domains of the chicken epidermal growth factor receptor. The C-terminal domain of the AEV-5005 erbB was complete, whereas that of AAV-5005 contained a 59 amino acid internal deletion (amino acids 993 1051 of the chicken epidermal growth factor receptor). Oncogenicity tests using retroviral constructs containing the erbB sequences from AEV-5005 and AAV-5005 demonstrated that both erbB genes caused erythroblastosis and that the 59 amino acid deletion conferred the ability to induce angiosarcoma. The 59 amino acid deletion also caused increased levels of erbB autophosphorylation in cells grown in the presence of sodium orthovanadate. PMID- 1408144 TI - Cooperation between the H-ras oncogene and a truncated derivative of the v-myb oncogene in transformation of hamster embryo fibroblasts. AB - The ras oncogenes alone fully transform established (immortalized) rodent fibroblasts in a few days, but generally transform early-passage fibroblasts only partially, unless their action is complemented by that of a nuclear, immortalizing, oncogene. Here we show that transfection of second-passage Syrian hamster embryo fibroblasts (HEFs) by the EJ-H-ras oncogene coupled to the neo gene, followed by selection with G418, gives rise to apparently normal, or only slightly transformed, clonal colonies, only a few of which become established. The study of two established clonal lines showed that they acquired only after some weeks, and stepwise, the main characteristics of full neoplastic transformation, i.e. anchorage independence, reduced requirement for serum growth factors and tumorigenicity. Later both clonal lines became increasingly tumorigenic and completely independent of exogenous growth and attachment factors, without increase in the expression of the H-ras oncogene. Transfection of one of the clones, early after its isolation, with a truncated derivative of the nuclear v-myb oncogene devoid of its transcriptional negative regulatory domain and able to partially transform chicken embryo fibroblasts [(myb(KXANM)] gave rise to more transformed cells, expressing both EJ-H-ras and myb(KXANM), which became tumorigenic earlier than the controls and remained more tumorigenic later on. With more efficient transfection techniques, numerous foci of fully transformed cells were subsequently obtained, in a few days, in cultures transfected sequentially with EJ-H-ras(neo) and myb(KXANM) and in cultures co transfected with the two oncogenes. Highly tumorigenic, serum-independent and immortalized clones expressing both oncogenes were obtained from these cultures. Hence, the truncated myb(KXANM) oncogene accelerate the stepwise transformation of unestablished HEFs by the EJ-HH-ras oncogene and, together with this oncogene, fully transforms these same cells in a single step. The two oncogenes acting in cooperation also induce cell immortalization, but myb(KXANM), by itself, is not an immortalizing oncogene. No cooperation was observed between EJ-H-ras(neo) and the unaltered v-myb oncogene. PMID- 1408145 TI - Hyperplasia of mouse mammary epithelium induced by expression of the Wnt-1 (int 1) oncogene in reconstituted mammary gland. AB - We have expressed the Wnt-1 (formerly int-1) oncogene in Balb/c mouse mammary epithelium in vivo, using a tissue reconstitution method in which primary cultures of mammary epithelial cells are infected with a retrovirus vector and then transplanted into mouse mammary fat pads from which the natural epithelium has been removed. Transplants carrying the Wnt-1 gene grew in a hyperplastic pattern, the duct epithelium showing abundant fine side-branches, but without development of clusters of alveoli. The hyperplasias were similar, but not identical, to transplants of normal epithelium in a mid-pregnant host. Transplants of epithelium that expressed Wnt-1 into mammary fat pads of male or ovariectomized females grew to form a similar three-dimensional pattern, but the extent of growth, and so presumably the rate of growth, was slower than in intact females, and there were no terminal end buds at the edges of the outgrowths. Thus, although Wnt-1 may enhance growth of epithelium in the male or ovariectomized-female environment, it does not restore the major mode of growth in the intact female, the extension of major ducts from terminal end buds. Normal epithelium showed no change in morphology when in close proximity to hyperplasia induced by Wnt-1, confirming the limited range of diffusion of Wnt-1 protein in vivo. Our results are consistent with the hypothesis that Wnt-1 acts principally by mimicking the signal that causes ducts to develop side-branches in pregnancy. PMID- 1408146 TI - Altered H1 histamine receptor signaling in Balb/3T3 cells transformed by v-K-ras and v-H-ras oncogenes. AB - Transformation of Balb/3T3 cells with the v-K-ras oncogene resulted in the expression of functional Ca(2+)-mobilizing receptors for histamine, whereas v-H ras-transformed Balb/3T3 cells failed to show a similar response to histamine. Stimulation of histamine receptors in v-K-ras-transformed cells produced a dose dependent increase in intracellular free calcium ([Ca2+]i), which was inhibited by the H1 histamine antagonist pyrilamine but unaffected by the H2 histamine receptor antagonist cimetidine. Histamine-mediated elevation of [Ca2+]i was partially inhibited by the removal of extracellular Ca2+, which indicates that the H1 histamine receptors mobilize intracellular Ca2+ and also promote Ca2+ influx. H1 histamine receptors were identified in both v-K-ras- and v-H-ras transformed Balb/3T3 cells, but not in untransformed cells, using the specific H1 antagonist [3H]-pyrilamine. Transformation of Balb/3T3 cells with the viral ras oncogene results in a complex regulation of H1 histamine receptors. K-ras and H ras transformation results in the expression of H1 histamine receptors; however, H1 receptor expression and Ca2+ mobilization are uncoupled in v-H-ras-transformed cells. PMID- 1408147 TI - Sequence and expression of a murine cDNA encoding PC326, a novel gene expressed in plasmacytomas but not normal plasma cells. AB - Using a subtractive cDNA approach we have identified a gene, PC326, expressed in 13 of 14 murine plasmacytoma cell lines, but not in any B- or pre-B-lymphoma cell lines. It expresses 4.6-kb and 5.2-kb mRNAs that encode a 747 amino acid protein containing two highly acidic domains flanking a novel, moderately acidic 20 amino acid sequence that is repeated 7.5 times. Sequence comparison identifies an additional 43 amino acid domain that is homologous to a repeated sequence found in the members of the beta-transducin gene family. The PC326 mRNA is detectable in testis but in no other murine tissues, including plasma cells induced by lipopolysaccharide stimulation of splenocytes. Somatic cell hybrids derived from plasmacytomas and fibroblast or T-cell lines have a fibroblastic or T-cell phenotype respectively. Unlike B-cell-specific genes (e.g. immunoglobulin), the expression of which is extinguished in these hybrids, PC326 mRNA appears to be irreversibly turned on in these hybrids. Since PC326 is not expressed in normal plasma cells, it appears that its expression is a cause or consequence of the tumorigenic process that generates murine plasmacytomas. PMID- 1408148 TI - Evidence that activation of the Egr-1 promoter by v-Raf involves serum response elements. AB - The constitutively active serine/threonine kinase encoded by the v-raf oncogene, v-Raf, activates the Egr-1 promoter in transient expression assays. To characterize the v-Raf-responsive transcriptional control elements, deletion mutants of the Egr-1 promoter were used in transient expression assays. A v-Raf expression vector was co-transfected into NIH3T3 cells with reporter chloramphenicol acetyl transferase (CAT) expression vectors under the control of the Egr-1 promoter or the Egr-1 promoter containing various deletions. Responsiveness to v-Raf was restricted to a region that contained repeated CC(A/T)6GG sequences, known as CArG boxes. CArG boxes form the core of serum response elements (SREs). v-Raf-induced Egr-1 promoter activation was lost by removal of the four tandemly repeated SREs. This region, between -425 and -250, which was necessary for v-Raf responsiveness, was also found to be sufficient for maximal Egr-1 induction by v-Raf when placed upstream from a minimal heterologous promoter. Three out of four SREs from this region were able to respond to v-Raf, however the activation of the individual SREs was lower than the clustered SREs. This cluster of SREs has previously been shown to be responsive to several mitogenic stimuli and the oncogene v-src. Thus, the SREs contained in this cluster may be an important target for cell division signals. PMID- 1408149 TI - Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group. AB - We have studied 146 ovarian tumours (94 carcinomas, 22 tumours of low malignant potential and 30 benign tumours) for evidence of allele loss on chromosome 17p and 17q sufficient to imply the proximity of a tumour-suppressor gene. We have examined two polymorphic loci (YNZ22.2 and BHP53) on 17p13 and one on chromosome 17q (17q23-qter). Loss of heterozygosity (LOH) was detected in 34/63 (54%) informative malignant tumours at YNZ22.2 and 22/47 (47%) at BHP53; on 17q, 45/64 (70%) had LOH. Allele loss was detected in a small number of benign and borderline tumours. There was a statistically significant difference between the patterns of allele loss in serous and endometrioid groups of tumours, and allele loss occurred with significantly greater frequency on 17q than on 17p. Comparison of all malignant tumours presenting with either localized (FIGO stage I/II) or widespread (FIGO stage III/IV) disease showed that, particularly on 17q, allele loss increases in the more advanced stages. The p53 tumour-suppressor gene is implicated in ovarian carcinogenesis, and our findings suggest that an important tumour-suppressor gene may be located in the region 17q23-qter. Loss of function in this gene may be responsible for the frequently observed rapid progression of serous-type adenocarcinomas to an advanced stage. PMID- 1408150 TI - c-Jun causes focus formation and anchorage-independent growth in culture but is non-tumorigenic. AB - The RCAS retroviral vector was used to express chicken and mouse cellular Jun proteins in chicken embryo fibroblasts. Both mouse and chicken proteins induced foci of transformed cells with low to moderate efficiency compared with viral Jun, but were as effective as the viral protein in promoting anchorage independent growth. Viral Jun and a recombinant between viral and cellular Jun induced tumors in 1-day-old chicks; the cellular Jun proteins were uniformly non tumorigenic. PMID- 1408151 TI - A retroviral sequence of the Chinese hamster ovary cell line. AB - A partial cDNA (B52) molecule with the characteristics of retroviral sequences was isolated from the Chinese hamster ovary (CHO) K1 cell line. The B52 cDNA contains 1184 nucleotides. The first 452 nucleotides (nt) are 71% homologous to the env gene of Moloney murine leukemia virus (MMLV) and murine endogenous retroviruses. The 139 amino acids predicted from the 452 nt have 82% homology with the carboxy-terminal amino acids of the env protein of MMLV. The remaining 732 nt have several features of a typical retroviral long terminal repeat (LTR). For example, the first 14 nt are identical to the 5' inverted repeat of the retroviral LTRs. The 41-nt sequence at the 3' end is common to the R region of retroviral LTRs. The 732-nt sequence was shown to have promoter activity. The activity is approximately twofold higher than that of the Rous sarcoma virus LTR, and 1.5-fold lower than that of the early promoter of SV40 virus. Two species of mRNA of 5.2 and 2.7 kb in size were readily detected by B52 cDNA in the CHO K1 cells. PMID- 1408153 TI - Special issue: Professor Fergus W. Campbell FRS. Contrasts in Vision 1991. Cambridge, United Kingdom, 5-6 September 1991. PMID- 1408154 TI - Publications by F. W. Campbell FRS. PMID- 1408152 TI - Mutational analysis of Max: role of basic, helix-loop-helix/leucine zipper domains in DNA binding, dimerization and regulation of Myc-mediated transcriptional activation. AB - The Max protein forms a heterodimeric complex with the Myc family of proteins and binds to DNA in a sequence-specific manner. We investigated the role of the helix loop-helix (HLH), leucine zipper (LZ) and basic domains of Max in protein complex formation, DNA-binding activity and transcriptional regulation. We mutagenized the basic, HLH and LZ domains of Max and studied the ability of the normal and mutant proteins to bind to DNA as both homo- and heterodimers and their ability to heterodimerize with Myc. Helix-1 and helix-2 regions of Max were found to be critical for homodimer formation and subsequent DNA binding, while the LZ was essential for heterodimer formation. In transient transfection assays the Myc protein functioned as a transcriptional activator while Max protein repressed the trans-activation observed with Myc. PMID- 1408155 TI - Imaging FWC. PMID- 1408156 TI - A festspiel in Cambridge for Fergus Campbell. PMID- 1408157 TI - Motion reveals spatial visual defects. AB - The question of how we can be unaware of the deficit in our (monocular) visual field, equivalent in size to 76 full moons, is examined. A new method of investigating the response to moving images on and near the blind spot has been found. The image of a computer-generated line, which is made to lengthen with time and pass over the blind spot, is seen as shorter than that of a similar, parallel line which passes outside the blind spot. This perceived difference in length corresponds to the actual width of the blind spot. Our unawareness of blind spots and scotomata is often described as involving some form of 'filling in' process. The rapid variation in cortical receptive field size, recently found to occur in response to stabilized images, may provide a general filling-in mechanism for the removal from perception of otherwise-distracting, stabilizing image regions (such as the shadows of blood vessels and clinical scotomata). PMID- 1408158 TI - New method based on random luminance masking for measuring isochromatic zones using high resolution colour displays. AB - A new method of measuring normal hue discrimination ellipses and dichromatic zones using a high resolution colour monitor is described. The test involves the detection of chromatic bars on a grey background (x = 0.305, y = 0.323) having a luminance of 34 cd m-2. Elements of the background matrix of square checks are varied randomly in luminance in space and time to provide random luminance masking (RLM) which compensates for differences in the relative luminous efficiency of different observers. The measurement technique provides a rapid and comprehensive colour vision test. Typical results are presented for normal trichromats, protanopes and deuteranopes without RLM and with the RLM set of 25%. The size of the discrimination ellipse in normal observers is the same in both viewing conditions, but the use of the RLM technique reveals the extent of the isochromatic zones in colour deficient observers. PMID- 1408159 TI - Pupillary responses to stimulus structure, colour and movement. AB - Pupillary responses to stimuli which favour the preferential stimulation of neural mechanisms involved in the detection of visual attributes such as colour, spatial structure, movement and light flux changes on the retina have been measured and compared. Pupil responses to a decrement in stimulus luminance (i.e., a flash of darkness), suggest that at least three components are involved in this response, their relative contribution being determined largely by stimulus size, contrast and presentation time. A comparison of pupil responses to gratings of equal and lower space-averaged luminance shows that the amplitude of pupillary constriction at grating onset for the equal luminance condition is about twice that measured with similar gratings in the lower luminance condition. Pupillary responses to chromatic isoluminant gratings are in general of longer latency when compared to responses of similar amplitude elicited by achromatic gratings. Small pupillary constrictions elicited by the onset of coherent movement in dynamic, random dot patterns are also demonstrated under stimulus conditions which eliminate pupillary responses to sudden light flux changes on the retina. The results support an earlier hypothesis which suggests that the onset of sudden changes in neural activity in the visual cortex when a visual stimulus is presented to the eye causes an overall perturbation which weakens transiently the regulatory inhibitory input to the pupillomotor nucleus. This, in turn, results in a transient increase in the efferent parasympathetic innervation of the iris sphincter muscle and hence the observed constriction of the pupil. The characteristics of the pupillary response reflect the properties of the mechanisms and the number of neurones which participate in the detection of each stimulus attribute. PMID- 1408160 TI - Non-linear processes in perceived region segregation: orientation selectivity of complex channels. AB - Models incorporating linear spatial-frequency- and orientation-selective channels explain many aspects of visual texture segregation. The inability of such models to fully explain texture segregation results, indicates that non-linear processes are also involved. One non-linearity that has been suggested is complex channels consisting of two stages of linear filtering separated by a rectification-type non-linearity (much like cortical complex cells). Here we further demonstrate the usefulness of complex channels in explaining texture segregation results and investigate the orientation-selectivity of the first stage of such complex channels. Our results suggest that the first stage is much more selective for orientation than are lateral geniculate nucleus cells, but that the first-stage orientation bandwidth is rather wide with some interaction occurring between perpendicular orientations. PMID- 1408161 TI - Geometrical optical analysis of photorefractive methods. AB - Photorefractive methods allow rapid measures of the refractive and accommodative state of infants and young children whose brief attention and co-operation limit the use of more traditional methods such as retinoscopy and autorefraction. Three methods have been defined: orthogonal, isotropic and eccentric. We provide a common geometrical optical analysis for these three methods where the photorefractive pattern is defined at the plane of focus of the camera. Since this plane is conjugate with the detector plane of the camera then the critical optical parameters can be defined without reference to the design of the camera by simply determining the relative magnification of the projected image of an object photographed at the camera's plane of focus. Specifically the pattern width CF (mm) over a photorefractor's working range can be defined for the isotropic and orthogonal methods as: [formula: see text] and for the eccentric method as: [formula: see text] where: K is a myopic refractive error of the eye (dioptres) (K Less than 0); P the distance of the flash source to the eye (dioptres); L the distance in front of the eye of the camera's plane of focus (dioptres) (L less than 0); GH the pupil diameter (mm); e the eccentricity of the flash source from the camera aperture (mm); M magnification of the image measured relative to the camera plane of focus. PMID- 1408162 TI - Counterphase dichoptic flicker is seen as its own second harmonic. AB - If a patternless field is modulated sinusoidally in time so that the luminance change in one eye is in counterphase to that in the other, the resulting flicker appears faster than if the modulation to both eyes has the same phase. If observers set the frequency and the amplitude of a comparison in-phase field so that it matches a neighbouring counterphase field, modulated at, say, 2.5 x its threshold, they set the frequency to twice the counterphase frequency, and the amplitude to a value that is, for a given frequency, a constant ratio of the modulation of the counterphase field. Counterphase stimulation thus appears to cause an internal second-harmonic signal. However, it is not possible to cancel this by adding a second harmonic component to the stimulus. PMID- 1408163 TI - Immediate colour constancy. AB - Colour constancy is traditionally interpreted as the stable appearance of the colour of a surface despite changes in the spectral composition of the illumination. When colour constancy has been assessed quantitatively, however, by observers making matches between surfaces illuminated by different sources, its completeness has been found to be poor. An alternative operational approach to colour constancy may be taken which concentrates instead on detecting the underlying chromatic relationship between the parts of a surface under changes in the illuminant. Experimentally the observer's task was to determine whether a change in the appearance of a surface was due to a change in its reflecting properties or to a change in the incident light. Observers viewed computer simulations of a row of three Mondrian patterns of Munsell chips. The centre pattern was a reference pattern illuminated by a simulated, spatially uniform daylight; one of the outer patterns was identical but illuminated by a different daylight; and the other outer pattern was equivalent but not obtainable from the centre pattern by such a change in illuminant. Different patterns and different shifts in daylight were generated in each experimental trial. The task of the observer was to identify which of the outer patterns was the result of an illuminant change. Observers made reliable discriminations of the patterns with displays of durations from several seconds to less than 200 ms, and, for one observer, with displays of 1 ms. By these measures, human observers appear capable of colour constancy that is extremely rapid, and probably preattentive in origin. PMID- 1408164 TI - Retinal information capacity and the function of the pupil. AB - When the pupil is opened to increase sensitivity there is a loss of image sharpness due to aberrations. This trade-off between sensitivity and sharpness is analysed theoretically by calculating the information capacity of the retinal image. The analysis uses optical measurements of image sharpness made at different pupil diameters. At each luminance there is a pupil diameter that maximizes information capacity. This optimum is close to the diameter adopted under normal viewing conditions. The optimum is broad, consequently the system tolerates inaccurate adjustment. The benefits of correctly adjusting the pupil are evaluated. At low light levels the advantage is 68%, at intermediate levels it falls to around 20% but under daylight conditions it increases to 52%. These advantages suggest that the primary function of the pupillary light reflex is to maximize acuity over a wide range of luminances. PMID- 1408165 TI - Facilitation of pattern recognition by cuing foveation with the luminance centroid as origin of the frame of reference. AB - The strategy for visual information processing must vary with the specific situation. We assume that in recognition of pre-learnt letter-like patterns under time-pressure conditions, mechanisms of selective attention are involved. We propose that, with simple stimuli, foveation is to the luminance centroids of such patterns, and if normally the latter has to be computed by the brain, cuing such information should improve performance. This assumption was tested on three subjects with five stimuli. In confirmation of the working hypothesis, we found significant improvements in performance (P = 0.01 or better) for each of the stimuli, with cuing to 'relevant' as compared with 'irrelevant' sites, and also when the point of foveation was nearer to the 'nodal' site. It is concluded that in pattern recognition processes, nodal regions are computed, the luminance centroid for example, for simple pattern stimuli. PMID- 1408166 TI - Binocular chromatic rivalry and single vision. AB - Depth perception is known to be impaired for chromatic equiluminant patterns. To investigate this phenomenon I have compared the effects of binocularly presented stimuli in the form of stripes, which contain only luminance information with similarly presented stimuli which contain only chromatic information. Observations of the reported percepts for the two conditions demonstrate that mechanisms of colour vision can impede stereopsis based on binocular fusion when the chromatic stripes are at, or even near, equiluminance, provided that their saturation is high. This observation is consistent with inhibitory interactions within the chromatic-sensitive neuronal groupings in the visual cortex. PMID- 1408167 TI - Visual evoked electrical and magnetic response to half-field stimulation using pattern reversal stimulation. AB - The visual evoked magnetic response to half-field stimulation using pattern reversal was studied using a d.c. SQUID coupled to a second order gradiometer. The main component of the magnetic response consisted of a positive wave at around 100 ms (P100M). At the time this component was present the response to half-field stimulation consisted of an outgoing magnetic field contralateral and extending to the midline. When the left half field was stimulated the outgoing field was over the posterior right visual cortex and when the right half field was stimulated it was over the left anterior visual cortex. These findings would correctly identify a source located in the contralateral visual cortex. The orientation of the dipoles was not that previously assumed to explain the paradoxical lateralization of the visual evoked potential. The results are discussed in terms of both electrical and magnetic models of the calcarine fissure. PMID- 1408168 TI - Rules for colour constancy. AB - Colours of objects tend to be constant regardless of the colour of the illuminant, therefore, regardless of the quanta catch of the retinal cones. Various mechanisms for this including context recognition, adaptation of retinal sensitivities and independent processing by receptor types have been proposed. These present experiments test the hypothesis that colours are determined by the normalized relationship between all colours in the field of view. In this hypothesis, colours are constant in classical experiments simply because changes of the illuminant do not disrupt the relationship between quanta catches across the field of view. The experiments consist of making sets of colour displays; each with the same relative quanta catches, but different absolute reflectances. 'Colour tautomi' arrays of five colour patches were printed using controlled amounts of yellow, magenta, cyan and black toners. The experiment began with a control 'colour tautomi' array of reflectances with measured relative quanta catches. New arrays of colours were then chosen that increased (or decreased) the reflectances, and quanta catches, a constant amount for the entire array. These changes were done independently for each receptor type. When these 'colour tautomi' are viewed in the room, each array has a different set of colours. When viewed in a restricted field of view, all arrays appear the same. In a further experiment new areas such as white are added to the display. Colour constancy is a field phenomenon controlled by the relative quanta catches in the field of view. Absolute colour constancy is controlled by the relative quanta catches in the field of view and the absolute quantum catches of the receptors. PMID- 1408169 TI - Springer's lines and Hermann's grid. AB - Hermann's grid is a complete matrix of black squares; Springer's figure has alternate squares whited out. Both figures generate illusory elements, bright and dark lines in the white spaces, with different elements seen from different distances. The visibility of these different elements is shown to be related to the detectability of sinusoidal gratings of wavenumbers corresponding to certain critical components of the Fourier decomposition of the figure. Evidence from the detection of gratings shows that near- and sub- (but not supra-) threshold contrasts are subject to a fourth power compression which shows, in the present figures, as a defect in the percept, equivalent to the deletion of (a part of) the corresponding Fourier components. There are some residual problems in understanding the perception of Hermann's grid. PMID- 1408170 TI - Mutual rod-cone suppression within the central visual field. AB - Under mesopic conditions the contrast sensitivity of the central visual field is reduced as the result of a non-linear interaction between rod- and cone-mediated signals, each of which is capable of higher sensitivity in isolation. The interaction is produced only when the rod-mediated system is driven at flicker rates above 6 Hz. This finding bears upon how rod and cone signals are combined and therefore affects our interpretation of the significance of the relationship between retinal illuminance and both contrast sensitivity and temporal resolution. PMID- 1408171 TI - Using distinctive Fourier components to discriminate between complex patterns. AB - Observers discriminated between a plaid pattern formed by summing vertical and horizontal cosine gratings, and a plaid formed by multiplying the gratings. Such patterns are alike with respect to many non-Fourier primitives, but differ in the Fourier domain by diagonal components which are present in the plaid formed by multiplication, but not in the one formed by summing. When discrimination performance is related to the contrast of the diagonal components, it is found that the contrast threshold for discrimination is approximately the same as the threshold for detection of the isolated components. However, the psychometric function for discrimination is shallower than that for detection, suggesting the presence of masking. Despite the masking, the results support the proposition that discrimination processes may operate directly on the representations of local Fourier components. PMID- 1408172 TI - Image enhancement filters significantly improve reading performance for low vision observers. AB - As people age, so do their photoreceptors; many photoreceptors in central vision stop functioning when a person reaches their late sixties or early seventies. Low vision observers with losses in central vision, those with age-related maculopathies, were studied. Low vision observers no longer see high spatial frequencies, being unable to resolve fine edge detail. We developed image enhancement filters to compensate for the low vision observer's losses in contrast sensitivity to intermediate and high spatial frequencies. The filters work by boosting the amplitude of the less visible intermediate spatial frequencies. The lower spatial frequencies. These image enhancement filters not only reduce the magnification needed for reading by up to 70%, but they also increase the observer's reading speed by 2-4 times. A summary of this research is presented. PMID- 1408173 TI - Interactions between colour and luminance contrast in the perception of motion. AB - It has been demonstrated widely that at isoluminance moving chromatic stimuli are seen to be stationary or moving more slowly than their luminance counterparts. We have examined the effect on perceived velocity of adding luminance contrast to an isoluminant chromatic stimulus. We show that moving luminance contrast 'captures' colour so that a combined colour and luminance stimulus is seen moving as a unified percept. However, in the presence of colour contrast, significantly higher levels of luminance contrast are required to achieve a veridical velocity than for monochromatic stimuli with only luminance contrast. We show that this interactive effect between colour and luminance contrast cannot be fully explained by a threshold masking of luminance by colour contrast. The effect suggests that a breakdown in the veridical perception of velocity should be expected for colours with a wide range of associated luminance contrasts and not just for those at the point of isoluminance. PMID- 1408174 TI - Use of interferometric visual stimulators in optometry. AB - Professor Fergus Campbell and colleagues pioneered the use of the interferometric visual stimulator as a tool for separating optical from neural factors which limit spatial vision. The device is now commercially available as a clinical instrument which 'bypasses the optics of the eye' to measure the potential visual acuity of the neural portion of the visual system. However, the clinician needs to be aware of limitations of current instrument designs and recent advances in our understanding of peripheral vision, to correctly interpret patient data gathered with these devices. PMID- 1408175 TI - Visual responses to reward-related cues in inferior parietal lobule. AB - A sample of 263 neurones was recorded in area 7a of the parietal lobe, in a monkey performing a reach task to visual targets displayed on a touch-sensitive videomonitor. The task had been operantly conditioned on food or juice rewards, and 78 (30%) of the units showed activity changes linked in some way to the reward. For most of these cells, the response was to the approach of the trainer's hand with the food reward. This specific visual response was similar irrespective of the direction of approach. Six cells increased discharge as soon as the task was completed in apparent anticipation of the reward. Another two neurones responded to missing a reward: they fired vigorously if the videoscreen was blanked in mid-trial because a target was not correctly touched. In many cases (40/78) the same cells responding to some aspect of the reward also responded to visual cues given during the task, especially the presentation of the target location. Reward-related activity in area 7a probably results from an integration of the visual and limbic inputs to this region, such that visual information which foretells behaviourally important events is emphasized. PMID- 1408176 TI - Orientation anisotropy: some caveats in interpreting group differences and developmental changes. AB - We tested 220 children aged 7-12 yr and 20 university students for visual contrast sensitivity at spatial frequencies of 1.2-21.9 c/deg for vertical, horizontal and oblique sinusoidal gratings. Males had higher mean sensitivity then females and adults had higher mean sensitivity than children. Sensitivity was greater for cardinal than oblique orientations, and this oblique effect increased with spatial frequency and mean sensitivity, and with age in children. Developmental growth of oblique anisotropy can be explained by growth in contrast sensitivity. Different sizes of oblique effect were found between groups living in different locations, but variations were mainly linked to differences in age and contrast sensitivity. Genetic or environmental interpretations of group differences should be treated with caution. Other anisotropies occurred (horizontal was better than vertical and right than left obliques), but these differences were small and irregular and may represent response biases rather than neurological effects. PMID- 1408177 TI - Coloured shadows described in a cone contrast space. AB - Two effects which can modify the appearance of a colour seen in a context compared to isolation are chromatic induction and colour constancy. These effects transform colour in ways which depend on the visual system rather than physical characteristics of light and surfaces. They need not reflect different processes within the visual system, indeed, chromatic induction has been attributed to the same processes as those involved in constancy, or, as an error of the visual system attempting to achieve constancy. This hierarchy is not necessary: both constancy and induction may result from the same processes without requiring that one promotes the other or that constancy is a goal of the visual system. This study examines induction in terms of cone contrasts in a coloured shadow display, part of a study to establish a relevant measure of contrast and its role in chromatic induction and colour constancy. PMID- 1408178 TI - Colour, contrast and the visual evoked potential. AB - Visual evoked potentials exhibit interesting morphological changes when they are elicited by checkerboards of different spatial and chromatic contrast, counterphasing in the foveal and lower macula field. The characteristic, positive wave of the phase-reversal visual evoked potential, for example, is preceded by an increasingly prominent negative peak as luminance contrast progressively increases above 10% and, at isoluminance, the response to red and green checkerboards becomes a predominantly monophasic negative wave. To study the nature of the morphological change we synthesized these waveforms with a computer simulation consisting of Gaussian components. The amplitudes of positive and negative components were altered until the synthesized response was closely similar to the recorded data. These Gaussian components have response characteristics which are identified with those of magnocellular and parvocellular neurones. PMID- 1408179 TI - Amplitude spectra of natural images. AB - Several studies have suggested that the amplitude spectra of photographs of natural scenes are remarkably similar and have the form: amplitude varies; is directly proportional to spatial frequency-1.0. This is, of course, a straight line with slope of -1.0 when plotted on double logarithmic coordinates. We have examined the amplitude spectra of 135 digitized photographs of natural scenes and have found that relatively few images conform exactly to the suggestion. About 25% of the images in our sample have spectra which show significant curvature when plotted on log-log coordinates. The best-fitting regression lines have slopes that range from -0.8 to -1.5; the average slope is -1.2, rather steeper than previously suggested. PMID- 1408180 TI - Different spatial tunings for ON and OFF pathway stimulation. AB - We compared the spatial tuning of sensitivity to luminance increments and decrements in three types of localized stimulus presentation with a smooth spatiotemporal envelope. The first type consisted of spatiotemporal Gabor grating functions with either a positive or a negative bias in luminance. The spatial tuning showed a substantially narrower bandwidth and greater peak sensitivity for the positive Gabors. A similar description could be applied to the results for detection of spots with a 2-D difference-of-Gaussian profile, although the shape of the tuning function differed in several respects. We also used the biased Gabor modulation in a contrast self-masking paradigm, where the increment (or decrement) was presented against a steady background with the same spatial configuration, over a range of base contrasts. At medium spatial frequencies the biased masking functions were similar to those typically found for unbiased gratings, in showing a threshold facilitation (dipper) at low contrast, and sub Weber masking behaviour at higher contrasts. At low spatial frequencies, however, a pronounced asymmetry appeared. Stimuli with a positive bias again showed typical masking behaviour, but a virtually flat masking function was obtained for negative bias stimuli. We conclude that stimuli without abrupt luminance transients reveal pronounced differences in the spatial tuning of responses to positive and negative stimuli, which probably reflect differences in the neural connectivity of the ON and OFF processing systems. PMID- 1408181 TI - Effect of myelination on the conduction velocity of optic nerve fibres. AB - It was proposed by Rushton in 1951, from theoretical considerations, that myelinated fibres less than 1 micron in diameter would conduct more slowly than unmyelinated fibres of the same size and that myelinated fibres below about 0.7 micron would not conduct at all. The experimental data on which he based his theory are all from the peripheral nervous system where small myelinated fibres are rare, and no experimental verification of Rushton's hypothesis has been attempted. In mammalian optic nerve, nearly all the fibres are myelinated; yet half have diameters below 1 micron, with many below 0.7 micron. The many studies of conduction velocities in the visual system enable a test of Rushton's hypothesis to be made. We have examined the correlations between conduction velocity and fibre diameter from a wide range of published studies of the mammalian visual system. The results of our analysis suggest that the small myelinated fibres of the optic nerve and optic tract conduct action potentials more rapidly than is predicted by Rushton's hypothesis, while the unmyelinated axons within the retina actually conduct more slowly than predicted. There is no reason to believe, in this case, that myelination of a small axon will reduce its conduction velocity. PMID- 1408182 TI - Problems measuring contrast sensitivity in children. AB - A preliminary study measured the contrast sensitivity function (CSF) in 30 children (aged 3 months-5 years). Preferential looking techniques were used to assess CSF to sine wave gratings displayed on one of two screens. To find a meaningful contrast sensitivity procedure we compared the results with a shorter procedure using an edge stimulus. The following problems were encountered: measuring the contrasts required to detect four or five different spatial frequencies took time, resulting in boredom and loss of attention in our subjects; there was poor correlation between CSF and edge detection; an interesting artefact resulted in a plateau rather than a low frequency fall-off in the CSF of five of the children greater than 30 months old. This artefact may have resulted from peripheral rather than central retinal responses and/or motion artefacts in the stimulus onset. A follow up study with 41 additional children aged 3-36 months limited the contrast testing to that of the spatial frequency corresponding to the peak of the CSF. The shortened procedure, plus a lot of encouragement, resulted in higher contrast sensitivities in all but the oldest age group and successful monocular contrast measurements. In order to avoid artefacts arising from peripheral vision, children were encouraged to look at each screen before responding. PMID- 1408183 TI - New acuity test for toddlers. AB - Preferential looking is the technique of choice for measuring visual acuity in infants and young children. Most workers agree that the toddler age group, 1 to 3 years, is the most difficult to test. This is because of their short attention span and restlessness, but mostly because they find the grating target used in the test, frankly boring. The concept of the vanishing optotype chart offers alternative test targets, while utilizing the technique of preferential looking. We have designed a test which comprises a familiar shape (house, car etc.) on the upper or lower part of a neutral grey card. The shape is computer generated, and designed to fade completely when beyond the resolution limit. Acuity is determined by the width of the white lines making up the shape. As with conventional preferential looking, the observer notes the child's eye movements to determine the position of the target shape. Although picture naming is not required, the shapes help to maintain the child's interest in the test. The test is quick, and is successful with the toddler age group and older patients with intellectual impairment. PMID- 1408184 TI - Current perspective on microfluctuations of accommodation. AB - The collaboration of Fergus Campbell, Gerald Westheimer and John Robson in the 1950s produced insight into the nature of accommodation microfluctuations and instigated work which has led to the current view that the nominally steady-state accommodation response exhibits temporal variations which can be characterized by two dominant regions of activity: a low-frequency component (LFC less than 0.6 Hz) and a high-frequency component (HFC greater than or equal to 1.0 less than or equal to 2.3 Hz). A functional role has been attributed to these microfluctuations as they offer a means by which a directional cue could be derived from an even-error stimulus. However, there is no consensus regarding the respective contribution made by each of the dominant components in the accommodation control process. Using a newly-designed measurement and recording system we have conducted a series of experiments to investigate the nature and aetiology of the microfluctuations. The incidence and magnitude of microfluctuations in LFCs and HFCs for central and peripheral lens zones were investigated while five young emmetropic subjects viewed a near target. The form of the power spectra of the fluctuations was found to be similar for central and peripheral zones although an overall reduction in magnitude was observed in the periphery. The HFCs are thus a consistent feature of microfluctuations in central zones and not, as previously suggested, merely a spurious feature of peripheral zones. A significant between-subject variation in the location of HFCs was found and led us to consider the relationship between HFCs and other physiological systems which provide intraocular rhythmic variation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408185 TI - Preliminary observations concerning treatment of visual discomfort and associated perceptual distortion. AB - A system for therapeutic precision tinting is described. Some individuals who are subject to perceptual distortion of text no longer perceive the distortion when the text has a particular colour. A simple colorimeter enables an observer to illuminate text with light of a particular chromaticity, varying first CIE 1976 hue angle (huv), then saturation (suv), and then luminance, to obtain a setting that maximizes visual comfort and reduces any perceptual distortion. The colorimeter setting is then matched by a combination of tinted trial lenses. The combination uses only two dyes at a time from a selection of seven, unless a dark lens is required, when a third neutral (grey) dye is added. The subject observes both text and a normal scene when wearing tinted trial lenses. A variety of trial lenses are compared including those that match the colorimeter setting and others with similar hue angle. Spectacle lenses are then tinted so as to have a spectral transmission identical to that of the chosen combination of trial lenses. Certain patients with reading disorders, eye-strain, headaches or photosensitivity epilepsy report benefit when wearing spectacles tinted according to the above techniques. The physiological basis for the therapeutic effects is uncertain, but may involve a selective impairment of luminance or colour-difference channels. PMID- 1408186 TI - Dependence of stereomotion on the orientation of spatial-frequency components. AB - It is known that sensitivity to stereoscopic motion in depth is not based upon the fine analysis of static disparities but instead is based on the binocular combination of motion-sensitive mechanisms. We show in this paper that an 'aperture problem' arises for the analysis of motion in depth, just as it does for monocular motion sensitivity. We extend Adelson and Movshon's solution to the aperture problem by intersection of perpendicular constraints to the three dimensional case, and show that it predicts velocity matches for oblique gratings moving in depth, for orientations close to vertical. We show that binocular plaids give rise to motion in depth when the component orientations match in each eye, and the monocular motions are horizontal. The match velocities are consistent with intersection of perpendicular constraints. In three dimensions intersection of perpendicular constraints may be necessary, but is not a sufficient condition for the perception of coherent stereoscopic motion in depth. PMID- 1408187 TI - Area 21a in the cat and the detection of binocular orientation disparity. AB - Visual response properties were examined in 115 cells, recorded in area 21a of the cerebral cortex of anaesthetized and paralysed adult cats. Cells were binocular and had receptive fields consisting of a single uniform discharge region which fired with composite ON/OFF responses to stationary flashing stimuli. Most cells were sharply tuned for orientation, but this was unaffected by changes in stimulus length. This result is consistent with a model in which the cells of area 21a receive their input from C cells of the striate cortex. Evidence for this was obtained by studying the decline in the responsiveness in area 21a that accompanied the cooling of areas 17 and 18. There was little indication that the cells of area 21a were effective detectors of spatial disparity, but their sharp monocular orientation tuning and differences in the preferred orientation of ipsilateral and contralateral eyes hinted at a role in the detection of binocular orientation disparity. Our results, however, showed that the recorded binocular disparity curves could be accounted for by summing the two monocular contributions and there was no apparent novel binocular component. PMID- 1408188 TI - Report on the National Commission on AIDS. PMID- 1408189 TI - Strategies for constructing a guinea pig organ of Corti cDNA library and its potential use. AB - Mutations of genes common to several tissues or organs can lead to cellular damage, which may result in hearing impairment as part of a syndromic disorder. Mutations of genes that are unique to the organ of Corti would have a high probability of causing nonsyndromic hearing impairment. It is expected that such genes are involved in auditory transduction as well as in maintaining specific hair cell and supporting cell functions in the organ of Corti. Cloning and describing genes involved with nonsyndromic hearing impairment thus require the construction of a guinea pig cDNA library of the organ of Corti. PMID- 1408190 TI - Transgenic mice. Current applications to the study of the auditory and vestibular systems. AB - Understanding the variety of genetic disorders affecting the inner ear demands that we first comprehend the molecular mechanisms involved in its development. Mechanisms of development can best be understood by the study of mutant organisms. Progress in the study of mammalian development has been hampered by the difficulty inherent in the identification and isolation of mutated genes. Transgenic technology provides a direct experimental approach to the study of the control and tissue specificity of gene expression. Additionally, this technology allows new and exciting methods of human disease modeling. A by-product of this technology is the creation of insertional mutants, which provide a unique approach toward the identification of genes involved in a variety of developmental processes including those of hearing and balance. PMID- 1408191 TI - Genetic alterations in head and neck cancer. AB - Mutations of the ras gene family appear to be an uncommon genetic alteration in SCCHN. A common region of DNA amplification on chromosome 11q13 has been identified in SCCHN. A cluster of proto-oncogenes (int-2, hst-1, bcl-1, prad-1) has been localized to the 11q13 region. Studies are needed to determine the critical genes in 11q13 whose expression drive the amplicon. Mutations of the p53 tumor suppressor gene are the most common genetic alteration in SCCHN. The hope is that dysregulated oncogenes or tumor suppressor genes may be targets for specific therapy. PMID- 1408192 TI - Cytogenetics in head and neck cancer. AB - Cytogenetic analysis of cell lines has identified a number of chromosomal regions that are likely to contain the genes important in malignant transformation in HNSCC. Further work needs to be done comparing results from cells grown in culture with tumors from which they are derived to determine the applicability of cytogenetic analysis. Preliminary results suggest that some of the chromosome changes observed may correlate with a cell's response to radiation and as such could provide a tool for evaluating a patient's response to planned therapy. PMID- 1408193 TI - Hereditary and environmental factors associated with risk and progression of head and neck cancer. AB - The familial occurrence of head and neck cancers supports the role of heredity in this disease group. The roles of environmental and genetic factors are difficult to separate. There are several well-characterized entities, however, that are associated with risk and prognosis of head and neck cancer, including Lynch-II syndrome, Bloom syndrome, Fanconi's anemia, xeroderma pigmentosum, ataxia telangiectasia, and Li-Fraumeni syndrome. Mutagen-induced chromosomal damage is associated with an increased risk of multiple primary neoplasms and upper aerodigestive tract cancers. A possible reduction of genotoxicity, mediated by micronutrients, was demonstrated in vitro. Sister chromatid exchanges and micronuclei are useful exposure and disease markers. Metabolic changes (acetylation, DBQ phenotype, and the AH locus polymorphism) have been found to be associated with cancer of the upper aerodigestive tract. Most associations between histocompatibility antigens and solid tumors are relatively weak, probably because of the masking effects of environmental factors. Infections by HPV, EBV, and HSV have a causative or predisposing role in several types of head and neck cancer. Amplification and rearrangement of oncogenes may also play a role in carcinogenesis, and oncogene amplification may be associated with aggressive tumor behavior and unfavorable clinical prognosis. Ploidy of tumors seems to be an important determinant of survival and response to therapy. PMID- 1408194 TI - The role of peptide growth factors in head and neck carcinoma. AB - Peptide growth factors are proteins that stimulate cellular proliferation by binding to specific cell membrane receptors. Evidence is accumulating that abnormal regulation of growth factors may contribute to carcinogenesis. The epithelial growth factors, EGF and TGF-alpha, which share the same receptor, EGFR, may play a pivotal role in the development and maintenance of head and neck cancer; preliminary studies concerning TGF-beta and IL-2 are inconclusive. There is increased production of TGF-alpha and EGFR mRNA in the majority of fresh tissues and cell lines from patients with SCCHN. This increase results from transcriptional activation of the gene(s). Therapies directed at the regulation of gene transcription may be useful in chemoprevention or modulation of disease. Nuclear studies that target up-regulated growth factor receptors may improve the ability to detect microscopic regional metastatic disease. PMID- 1408195 TI - Gene localization by linkage analysis. AB - Traditional genetic approaches have led to the identification of defects underlying an impressive array of diseases. Genetic terminology, Mendel's laws, chromosomes and linkage, statistical methods for linkage analysis, genetic markers, multilocus mapping, strategies in linkage studies, linkage heterogeneity, and the future of linkage analysis are discussed in this article. The molecular basis for most disorders, however, cannot be gleaned because there is no identifiable primary metabolic disorder. PMID- 1408196 TI - Gene mapping of the Usher syndromes. AB - USH is an autosomal recessive group of diseases characterized by auditory impairment and visual loss owing to RP. Two common types of USH are known, types I and II. USH type I is characterized by a congenital severe to profound hearing impairment, absent vestibular function, and a progressive pigmentary retinopathy. Persons with type I do not find hearing aids useful, have delayed motor development, and experience progressive night blindness and peripheral visual loss, which usually begins in their second decade. USH type II is characterized by a congenital moderate to severe hearing loss with a down-sloping audiogram, normal vestibular function, and a progressive pigmentary retinopathy. Persons with USH2 find hearing aids beneficial, have normal psychomotor development, and experience progressive night blindness and peripheral visual loss, which usually begins in their third decade. Vestibular dysfunction is the best distinguishing hallmark to differentiate USH type I from type II. One USH type II gene (called USH2) has been assigned to chromosome 1q. One USH type I gene has been tentatively assigned to chromosome 14q. There are other USH genes that have not yet been localized. PMID- 1408197 TI - Finding the gene(s) for Waardenburg syndrome(s). AB - Waardenburg syndrome is a recognizable disorder characterized by autosomal dominant inheritance of pigmentary abnormalities of the eyes, hair, and skin sometimes associated with congenital hearing impairment. At least two different types of Waardenburg syndrome have been described. The different types of Waardenburg syndrome are differentiated as follows: type I, with dystopia canthorum; type II, without dystopia canthorum; and type III, without dystopia, with unilateral eyelid ptosis and skeletal abnormalities. Results of pooled linkage analysis done by a consortium of investigators suggests that Waardenburg syndrome type I is genetically heterogeneous, meaning that there is probably more than one genotype that can be associated with the findings typical of the syndrome. A mutated gene that can cause Waardenburg syndrome type I has been discovered. Either a single base pair substitution or an 18 base pair deletion in exon 2 has been found in affected individuals but is not found in unaffected members. Most likely, the mutated gene causes a perturbation in DNA binding of a paired domain, in turn having an effect on the regulation of other genes so the development and spatial orientation of cells and structures derived from the neural crest are affected. Forty years after Waardenburg syndrome was first described, a mutant gene has been found that is known to cause the syndrome. The process of discovery that has transpired in the time from syndrome description to gene identification has been one of steady progress and interdisciplinary cooperation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408198 TI - Genetic counseling for the deaf. AB - Genetic counseling is a process that emphasizes accurate diagnosis of hereditary conditions and communication of information to families. Genetic counseling involves systematic collection of family and medical history, a physical examination by a certified clinical geneticist, sharing of information with the family, and follow-up and support services. The issues that arise in genetic counseling can differ for every family and are often dependent on the degree of deafness present in the family, age of onset, and linguistic and cultural orientation. It is important for the genetic counselor to consider these factors in the provision of genetic services. With the increasing application of molecular genetics to the diagnosis and management of hereditary deafness and the increasing participation of families with deafness in research studies, the involvement of genetic counselors to provide information and education to consumers as well as medical professionals and researchers is becoming even more critical. The success of genetic counseling for the provision of information to families and the delineation of types of hereditary deafness through clinical and laboratory research is dependent on appropriate referrals by medical professionals, including otolaryngologists. A working relationship between otolaryngologists and clinical geneticists for the referral and evaluation of patients with hereditary deafness or deafness of "unknown" etiology is important. PMID- 1408199 TI - Ethical and cultural considerations in research on hereditary deafness. PMID- 1408201 TI - Molecular genetics of acoustic tumors. PMID- 1408200 TI - Genetic aspects of idiopathic speech and language disorders. AB - At the outset of this article, we posed the question of whether or not the current evidence from genetic studies of DLD and stuttering indicate that it would be fruitful to conduct studies aimed at determining the gene location for each of these disorders. As we pointed out, because these are behavioral development disorders, phenotypic variations and changes in characteristics through the life span pose problems when attempting to determine who is and is not affected. Further, because these disorders can be either idiopathic or secondary to a variety of causes, any genetic study must rule out or take account of cases secondary to other factors. Few studies conducted thus far have taken these problems into account, and the results must be considered tentative. Given these reservations, the results certainly point to a genetic component in both disorders, although the data collected thus far on DLD suggest a mendelian form of transmission. If further more intensive studies continue to support this model for DLD, linkage studies on this disorder are likely to be productive. PMID- 1408202 TI - [Results of surgical treatment in laryngeal cancer patients based on material of the Lublin Clinic of Otolaryngology]. AB - A group of 287 laryngeal carcinoma patients was discussed, who were operationally treated over the period of ten years (1974-1983). Three- and five-year-long symptomless survivals were presented taking into account: age, sex, environment, habits, development of cancer on the base of precancerous conditions, primary localisation, progression of cancer in the larynx, presence of nodular metastases and a degree of clinical progression. In a group of 206 patients treated only operationally there were 65% of 5-year-long symptomless survivals, in a group 61 patients treated by the combined method--33%, and finally in a group of patients with recurrence after irradiation treated operationally there were only 25% of 5 year-long survivals. PMID- 1408203 TI - [Investigation of variability in the vascularity of trapezius musculo-cutaneous flaps]. AB - The search on the human body cadavers was done to determine the exact localization of the various cutaneous island flaps depending on the course of the blood vessels. The latex solution stained with the prussian blue was injected directly into the thyro-cervical trunk or subclavian arteries. Afterwards the island musculocutaneous flaps from various regions of the trapezius muscle were performed. The whole number of the performed flaps were 20. The search confirmed the possibility of formation island flaps from various regions of the trapezius muscle. PMID- 1408204 TI - [Plastic surgery of the trachea after laryngectomy enabling breathing without a tracheotomy tube]. AB - Plastic operations of trachea which enable to breath without the tracheotomy tube post total laryngectomy were presented by authors. Those operations were performed immediately post laryngectomy or also some time post remove larynx operation. In the first case the suitable "modeled" fold of the skin is made, in the second case the metallic half-loops are implanted. Results authors have received so far are encouraged to use of those methods. PMID- 1408205 TI - [Concerning the technique of forming a tracheostomy after total laryngectomy]. AB - Many different techniques of the tracheostoma were presented. The rules making of the tracheostoma at Otolaryngological Clinic in Szczecin and the results of it were discussed. The importance of the free--of tube--tracheostoma was emphasized during the rehabilitation of the patient after total laryngectomy. PMID- 1408206 TI - [Concerning diagnosis and treatment of parotid neoplasms]. AB - This study is a review of 57 patients with tumours in the parotid glands who underwent surgery at the ORL Clinic in Bialystok. Malignant tumours constituted 17.5% of all parotid tumours and adenoid cystic carcinoma was the dominant type in this group. Pleomorphic adenomas were the most common benign tumour. The role of fine needle aspiration biopsy in diagnosis of parotid tumours is discussed. Superficial parotidectomy was the predominant form of treatment (47 cases). Total parotidectomy was done in 7 cases. The results of treatment are presented. PMID- 1408207 TI - [Controlled ENG examinations of patients with lack of induced unidirectional Ny]. AB - 19 patients have been checked by the ENG control examination who had demonstrated during first examination lack of evoked Ny in one direction. The control examinations have been conducted from a few months to 4 years after the first ENG examination. Obtained results showed out that lack of evoked Ny in one direction can be persist or can be improved by going into symmetrical directional preponderance, after that in some cases coming to restitution and integrum. It can be explained by the degree of brainstem reticular substance lesion. The obtained results from the study allow to conclude, that lack of evoked Ny in one direction and coming after it the symmetrical directional preponderance have a topo-diagnostic value. PMID- 1408208 TI - [Complications of tonsillectomy]. AB - The surgical treatment of the tonsils may cause different complications including even death. The author gives the examples of such complications and also pays attention to the importance of being cautious during this intervention. PMID- 1408209 TI - [Massive hemorrhage from the nose as a result of posttraumatic rupture of the internal carotid artery]. PMID- 1408211 TI - [Vertigo in patients with otosclerosis and post stapedectomy]. AB - The aim of the paper was evaluation of behaviour of the balance system in patients with clinical otospongiosis and after stapedectomy. The investigation was carried out in 131 otosclerotic patients. Before and post operation vertigo was noticed and the spontaneous nystagmus, positional nystagmus and directional preponderance in kinetic test were examined in ENG. Vertigo and objective symptoms of disturbance of the vestibular function were found in clinical otospongiosis, but postoperative subjective and objective symptoms were more frequently. PMID- 1408210 TI - [The influence of hearing aids on the ability of directional hearing in a free auditory field]. AB - The study was on subject of preservation of directional hearing in free auditory field, in horizontal plane in different stages of pathological lesions of the bearing organ with properly fits hearing aid from Viennatone as the behind-the ear hearing aid (model 116 PAD) and the hearing spectacles (model 90 AN). There were noticed in 50 percentage of subjects improvement in the directional hearing. The best results was obtained in unilateral deafness. The evidently amelioration was observed in front azimuths. The obtained improvement directional hearing was not proportional to the stage of hearing improvement. PMID- 1408212 TI - [Difficulties in diagnosis and treatment of refractory epistaxis]. AB - A case is described of surgically treated refractory epistaxis in a man aged 56 years. The role of angiography in the choice of suitable management was pointed out. PMID- 1408213 TI - [Cases of granular cell tumor (myoblastoma) in the larynx]. AB - Two patients suffering from very rare granular cell tumor of the larynx were observed at the ENT Department of Medical School in Szczecin in the period 1986 to 1990. In one case the tumor located in the intra-arythenoid region was treated by tyreotomy. In the second case the tumor contained comisura anterior and cricothyreoidea region and was resected by subglottic laryngectomy. The functional results of the treatment were satisfactory. PMID- 1408214 TI - [A case of schwannoma in the floor of the oral cavity]. PMID- 1408216 TI - [Scientist's report of a month's stay in Copenhagen (20.IX.--19.1989)]. PMID- 1408215 TI - [Several generations of developmental abnormalities of the branchial arches and cleft]. AB - Morphology and pathological mechanism of congenital anomalies of the first and second branchial arch and cleft were discussed. Present views on heredity of those malformations have been also presented. Five examples of familial occurrence of microtia and cleft are described. PMID- 1408217 TI - A tribute to Jack R. Anderson, MD. PMID- 1408218 TI - Passive exposure to cocaine in medical personnel and its effect on urine drug screening tests. AB - This report studies the importance of passive exposure of medical personnel to cocaine hydrochloride and its impact on urine screening testing. Eleven medical staff members were exposed to cocaine hydrochloride by means of aerosol and cutaneous application, similar to that which may occur in medical practice. Urine drug screening tests were negative for everyone tested. This finding is supported by known drug kinetics. It is unlikely that a single passive exposure of medical staff to cocaine hydrochloride will produce a positive urine screening test. In all cases of positive urine tests, contaminants should be tested for which may indicate a source of the drug. The routine use of gloves and masks--which is recommended to prevent HIV infection--should further decrease medical personnel's passive exposure to cocaine hydrochloride. PMID- 1408219 TI - Indications for open cervical node biopsy in HIV-positive patients. AB - Open node biopsy was the method of choice for diagnosing human immunodeficiency virus (HIV) infection before serologic testing became available. Currently, the otolaryngologist is often called on to assist in the management of HIV-positive patients with troublesome cervical adenopathy. Today's questions are: what is the place of fine-needle aspiration (FNA), and when is open cervical node biopsy indicated. A retrospective review was undertaken of 93 consecutive cervical node biopsies performed by our department during the 5-year period from 1985 to 1989. Twenty of the patients who underwent biopsy were HIV-positive. Of these twenty, ten carried an established diagnosis of acquired immune deficiency syndrome (AIDS). Seventeen of these patients underwent FNA before biopsy. In the eight patients with persistent generalized lymph-adenopathy (PGL) and nontender, nonenlarging nodes, pathologic analysis revealed lymphoid hyperplasia. Five of these patients had antecedent FNA, none demonstrating any pathologic changes. Of the twelve patients with enlarging or tendon nodes, the diagnosis of mycobacterial adenitis was made in eight, Nocardial infection in two, Burkitt's lymphoma in one, and metastatic Kaposi's sarcoma in one. In four of the patients diagnosed with mycobacterial infections, FNA yielded cytologic evidence of acid fast bacilli and open lymph node biopsy added nothing. In contrast, FNA failed to reveal the diagnosis in both patients with Nocardial infection, and in the two patients with neoplastic disease. We conclude that cervical node biopsy is not indicated in the HIV or AIDS patient with nontender or nonenlarging nodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408221 TI - Lipoma of internal auditory canal. AB - Lipoma of the internal auditory canal is a rare tumor. Clinically, it presents like an acoustic tumor. The diagnosis can be made with the use of a magnetic resonance imaging showing a high intensity on T1- and low intensity on T2 weighted image with no enhancement. Pathologically, this is a soft, smooth, yellow tumor with some fat in it that can resemble grossly any acoustic tumor. The lipoma is intermixed with the eighth nerve and can be adherent to adjacent structures. The growth of a lipoma can be slower than an acoustic tumor. A patient diagnosed with lipoma of the internal auditory canal can often have quite good hearing. As an alternative to surgical removal, another therapeutic option is to watch the growth of the lipoma with periodic magnetic resonance imaging, probably on a yearly basis initially. PMID- 1408220 TI - Bilateral electrocochleographic findings in unilateral Meniere's disease. AB - At present, electrocochleography is the only proven investigation that can demonstrate objectively the presence of endolymphatic hydrops. The electrophysiologic recordings in response to sound stimuli show an enhancement of the negative summating potential in these cases. It is well established that patients with unilateral Meniere's disease have a high likelihood of development of the disease bilaterally in the fullness of time. Using transtympanic electrocochleography in 40 patients who manifested unilateral clinical Meniere's disease, we have recorded bilateral abnormalities indicative of endolymphatic hydrops in 35% of cases. The early recognition of incipient Meniere's disease in the asymptomatic contralateral ear of a patient with known unilateral disease has obvious profound implications for patient management. PMID- 1408222 TI - Prognostic value of evoked and standard electromyography in acute facial paralysis. AB - Ninety-one patients with idiopathic (n = 62) and traumatic (n = 29) facial paralyses were available for evaluation at least 1 year after the onset of paralysis. In nine cases of idiopathic paralysis and in 12 cases of traumatic paralysis, total intratemporal nerve decompression was performed. The remaining patients were treated with steroids alone. All patients underwent evoked electromyography (EEMG) testing within 2 weeks of the onset of paralysis. Facial nerve recovery was graded using the House-Brackmann facial nerve recovery scale. Subjects were grouped according to maximal decline of compound muscle action potential (CAP), as determined by EEMG, and by level of recovery 1 year after onset of paralysis. Among patients who did not undergo surgical decompression of the facial nerve, incomplete clinical recovery (grade III or higher) was significantly associated with CAP decline of greater than 90% (p less than 0.05) for idiopathic paralysis. In contrast, there was no significant association between CAP decline of greater than 90% and clinical outcome in traumatic paralysis. These findings support previous reports of the prognostic value of EEMG in idiopathic facial paralysis, but suggest that this test may have less predictive value in the evaluation of facial paralysis as a result of trauma. PMID- 1408223 TI - Partial endoscopic middle turbinectomy augmenting functional endoscopic sinus surgery. AB - Endoscopic sinus surgery has gained acceptance in the otolaryngologic community as an effective and safe method of treating inflammatory disease of the paranasal sinuses. At our institution, partial endoscopic middle turbinectomy has become a standard component of the procedure and our experience is reported. Middle turbinectomy enhances surgical exposure, specific anatomic anomalies are more completely corrected, and subpopulations of patients at risk for failure because of their underlying disease enjoy decreased rates of synechiae formation and closure of the middle meatus antrostomy when followed over time. Photodocumentation of the surgical technique and a discussion regarding the impact of middle turbinectomy on normal nasal physiology are presented. It is reported that the procedure is safe, and no complications directly attributable to middle turbinectomy (including atrophic rhinitis) are reported in a series of 298 patients. PMID- 1408224 TI - Mandibular lingual releasing approach. AB - The mandibular lingual releasing approach to oral cavity and oropharyngeal tumors provides excellent visualization for resection while integrity of the mandibular arch is preserved. A lingual floor-of-mouth flap is created, which allows delivery of these structures directly into the neck without lip splitting, mandibulotomy, or mandibulectomy. The procedure was carried out on 15 patients between 1987 and 1991, with followup ranging from 2 to 50 months. Nine patients had received previous radiation, whereas planned postoperative radiation was administered to five patients. The visualization afforded by this technique was very good, in that 12 patients had clear margins of resection. Three patients had close margins; recurrent disease developed in one of these patients 18 months later. Twelve of the patients were able to maintain their weight with an oral diet alone. Four postoperative fistulae occurred, three of these were in patients who had not been previously irradiated. The single fistula that did not spontaneously heal occurred in a patient who had received previous radiation and was also on long-term corticosteroids. Mandibular osteoradionecrosis developed in two patients who received postoperative radiation. The complication rate after previous radiation is acceptable; however, there is risk of mandibular osteoradionecrosis after high-dose postoperative radiation. PMID- 1408225 TI - The canalith repositioning procedure: for treatment of benign paroxysmal positional vertigo. AB - The Canalith Repositioning Procedure (CRP) is designed to treat benign paroxysmal positional vertigo (BPPV) through induced out-migration of free-moving pathological densities in the endolymph of a semicircular canal, using timed head maneuvers and applied vibration. This article describes the procedure and its rationale, and reports the results in 30 patients who exhibited the classic nystagmus of BPPV with Hallpike maneuvers. CRP obtained timely resolution of the nystagmus and positional vertigo in 100%. Of these, 10% continued to have atypical symptoms, suggesting concomitant pathology; 30% experienced one or more recurrences, but responded well to retreatment with CRP. These results also support an alternative theory that the densities that impart gravity-sensitivity to a semicircular canal in BPPV are free in the canal, rather than attached to the cupula. CRP offers significant advantages over invasive and other noninvasive treatment modalities in current use. PMID- 1408226 TI - Computer-aided three-dimensional measurement of the human vestibular apparatus. AB - Using a computer-aided three-dimensional reconstruction and measurement method, 12 measurements were made to determine the dimensions of the maculae, cristae ampullares, and semicircular canals in 18 temporal bones from nine pairs of age matched male and female individuals (1 day to 76 years old). The surface areas of the utricular and saccular maculae were significantly larger in male than in female specimens (two-way analysis of variance, F = 9.00, df = 1, p less than 0.01; F = 4.57, df = 1, p less than 0.05, respectively). The width of the utricular macula and the length of the saccular macula were also significantly greater in male than in female specimens (two-way analysis of variance, F = 5.17, df = 1, p less than 0.05; F = 4.33, df = 1, p less than 0.05, respectively). Finally, the three semicircular canals were larger in diameter in male vs. female specimens; this difference was statistically significant for the superior semicircular canal (two-way analysis of variance, F = 10.74, df = 1, p less than 0.01). By contrast, none of these dimensions of those vestibular structures showed any significant change in size with advancing postnatal age. We propose from these findings that there appears to be sexual dimorphism in the vestibular apparatus. PMID- 1408227 TI - Cochlear implants in children: reliability of computed tomography. AB - Preoperative temporal bone computed tomography (CT) can demonstrate anatomic details relevant to surgical management and is therefore essential in the presurgical evaluation of patients receiving cochlear implants. The purpose of this study was to evaluate preoperative CT studies and compare them to surgical findings in 34 children who received the Nucleus multichannel cochlear implant. The focus of this report is to discuss the dependability of CT scans in predicting surgical findings at the time of cochlear implantation. Results indicate that agreement of CT interpretations with surgical findings is partially related to the etiology of hearing loss and the experience of the surgeon and neuroradiologist. Advantages and limitations of the CT scans in predicting surgical findings are discussed. PMID- 1408228 TI - Surface sensibility of the floor of the mouth and tongue in healthy controls and in radiated patients. AB - Increased areas of anesthesia in the oral cavity have been shown to significantly impair oral function in normal individuals. In patients who undergo oral cavity reconstruction, loss of sensation plays a major role in producing disturbances in postoperative oral function. Free tissue transfer techniques have permitted the problem of sensory loss to be addressed through the use of sensate cutaneous free flaps, in which microneural anastomoses are performed between a sensory nerve supplying the flap and a recipient nerve in the head and neck. To critically assess the results of such reconstructions, the effect of sensory restoration on oral cavity rehabilitation must be studied. As a first step toward this goal, normal values for sensory discrimination of the floor of mouth and tongue are needed. Previous studies of oral sensation failed to examine the ventral tongue and floor of mouth. The purpose of this study is to determine the surface sensibility of these regions in healthy patients and in patients who received radiation therapy to the oral cavity. Sensation was evaluated using static and moving two-point discrimination in 90 healthy subjects divided equally into three age groups: 20 to 40 years, 41 to 60 years, and 61 to 80 years. In addition, 20 patients who received radiation therapy were studied. The mucosa of the dorsal and ventral aspects of the lateral tongue, tongue tip, and floor of mouth was examined. The tongue tip is the most sensitive area, followed by the dorsal lateral tongue, ventral lateral tongue, and floor of mouth. The effects of age and radiation therapy on sensory discrimination are discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408229 TI - Pain after surgery for acoustic neuroma. AB - Postoperative pain after surgery in the cerebellopontine angle (CPA) is acknowledged to occur, but is rarely taken into account as a factor in the analysis of morbidity of such surgery. It is widely acknowledged that some patients, having undergone such surgery, particularly by means of the suboccipital approach, report significant post-operative pain and headache. This study was undertaken to determine the incidence and severity of pain after excision of acoustic neuromas and to establish whether this differed between the suboccipital and translabyrinthine routes. Ninety-one percent of all patients (n = 58), who had the suboccipital approach used for removal of their tumor, were surveyed. A smaller group (n = 40), matched for tumor size, age, and sex, but in whom the translabyrinthine approach was used, was similarly studied. A standard questionnaire, designed to detect and quantify postoperative pain, was administered to each patient. Of patients who underwent tumor excision by means of the suboccipital approach, 63.7% experienced significant local discomfort and headache, whereas this was notably absent in all those who had undergone translabyrinthine excision. In view of the significant morbidity noted to follow the suboccipital approach, several modifications of the surgical technique used were devised. PMID- 1408230 TI - Combined infrahyoid and inferior constrictor muscle release for tension-free anastomosis during primary tracheal repair. AB - Although tracheal stenosis is not a common clinical entity, it still presents a significant management problem, despite recent endoscopic advances. Surgical correction by resection and primary anastomosis is the preferred treatment, provided the repair can be performed without excessive tension. Various release techniques have been described in order to achieve mobility and, thereby, a tension-free anastomosis. This article presents a combined infrahyoid muscle and inferior constrictor muscle release to assure maximum mobility of the laryngotracheal complex, thus allowing tension-free closure. A series of ten patients who underwent primary repair using the combined technique is presented, and the operative technique is described. The indications, age, length of stenosis, and minimum 1 year followup of these patients are presented, as well as perioperative management and complications. The success rate with this technique is 90%. PMID- 1408231 TI - Community-acquired methicillin-resistant Staphylococcus aureus infections in otolaryngology. AB - Soon after the introduction of methicillin, strains of Staphylococcus aureus resistant to methicillin were reported. Methicillin-resistant Staphylococcus aureus (MRSA) has become a common hospital pathogen, often resistant to multiple antibiotics, while causing significant morbidity and mortality. Community acquired MRSA infections have been infrequently documented. Most reports have been associated with intravenous drug abuse. This report reviews 15 patients with community-acquired MRSA infections of the head and neck. None admitted to intravenous drug use. Additionally, no patient was known to be a healthcare worker. The MRSA strains showed antibiotic susceptibility and resistance profiles different from typical hospital-acquired MRSA isolates. All but one infection resolved with adequate surgical or appropriate antibiotic therapy. Clinicians should become aware of the possibility of community-acquired MRSA in the patient who has had continued infection despite antibiotic therapy. PMID- 1408232 TI - Soft tissue effects of the THC:YAG laser on canine vocal cords. AB - Recently, a laser based on a thulium-holmium-chromium (THC) doped Yttrium aluminum-garnet (YAG) rod has been developed that produces light of 2.15 microns wavelength and can be transmitted through a low OH- silica fiberoptic cable. This wavelength falls on one of the peaks of the energy absorption spectrum of water. Thus, the THC:YAG laser eliminates the disadvantage of a cumbersome delivery system found in the CO2 laser while still providing precise cutting and minimal tissue injury inherent in lasers emitting light absorbed by water. We evaluated the soft tissue effects of this laser on canine vocal cords. Ablative lesions were produced by the THC:YAG laser and histologically examined on postoperative days 1, 7, and 28. Results indicate that the depth of tissue penetration is easily controlled and the healing response to tissue injury is comparable to that of the CO2 laser. The THC:YAG laser should prove to be a superior laser for use in otorhinolaryngology, especially when adapted to a flexible endoscope. PMID- 1408233 TI - The riddle of the uvula. AB - Since ancient times, the uvula has been a subject of interesting and contradictory observations. On the one hand, it was regarded as having a functional role in speech and in immunology, but on the other hand it was regarded as a potentially hazardous organ, possibly responsible for sudden infant death syndrome. None of these hypotheses, however, has been proved. In a previous study on patients undergoing uvulopalatopharyngoplasty, we suggested that the most important function of the uvula is connected with the muscularis uvula. Its function could be related to drinking while bending over. This previous assumption was that the uvula is a phylogenetic remnant from mammals that drink while bending their neck downward. In the present study, the soft palate of eight different mammals was macroscopically and microscopically studied and compared. Of all animals in the study, a small underdeveloped uvula was found only in two baboons. We found that the human uvula consists of an intermix of serous and seromucous glandular masses, muscular tissue, and large excretory canals. The serous and seromucous glands are absent in the other mammals. Thus, the uvula is a highly sophisticated structure, capable of producing a large quantity of fluid saliva that can be excreted in a short time. Both uvula and speech serve to differentiate human beings from animals. Our conclusion is that the uvula is possibly an accessory organ of speech, and may be another marker of human evolution that differentiates man from other mammals. PMID- 1408234 TI - Intracordal injection increases glottic closing force in recurrent laryngeal nerve paralysis. AB - Glottic closing pressure during swallowing was measured in the cat with a catheter pressure transducer to study the effectiveness of intracordal injection in increasing glottic pressure in unilateral recurrent laryngeal nerve paralysis. Swallows were elicited by pouring water into the pharynx while the animal was under light anesthesia with ketamine. Peak pressure of the glottic closure for the control group during deglutition was 68.0 +/- 10.5 mm Hg (mean +/- standard deviation). Peak pressure decreased to 22.0 +/- 3.6 mm Hg just after sectioning of the unilateral recurrent laryngeal nerve, and rose to 39.8 +/- 8.3 mm Hg by silicon injection into the paralyzed vocal fold. In a study of chronic cases 1 month or more after unilateral recurrent laryngeal nerve section, peak pressure was 49.1 +/- 23.4 mm Hg, and varied widely from 21 to 92 mm Hg because of differences in the position of the paralyzed vocal fold and the degree of compensation by the unaffected vocal fold. In the group that had the paralyzed vocal fold fixed in the median position, peak pressure was almost the same as that of the control group. When the paralyzed vocal fold was fixed in either the paramedian or lateral position, peak pressure was 33.3 +/- 7.0 mm Hg. This value was significantly elevated to 45.8 +/- 10.4 mm Hg by injection of silicon, though it remained lower than that of the control. These results suggest that the decrease in glottic closing force during swallowing as a result of unilateral recurrent laryngeal nerve lesion is compensated for by the unaffected vocal fold to some degree and is improved by intracordal injection. PMID- 1408235 TI - Microcystic adnexal carcinoma of the lower lip. PMID- 1408236 TI - Paranasal phycomycosis in the immunocompetent host. PMID- 1408237 TI - Parathyroid adenoma with cervical tracheal compression. PMID- 1408238 TI - Thyroid hemiagenesis in a patient with a parathyroid adenoma. PMID- 1408239 TI - The Nucleus multichannel cochlear implant: comparison of scala tympani vs. scala vestibuli electrode placement in a single patient. PMID- 1408240 TI - Bazex syndrome. PMID- 1408241 TI - Acoustic neuroma presenting as a middle ear mass. PMID- 1408242 TI - Intratracheal esophagus resulting from displacement by a large goiter. PMID- 1408243 TI - Canalization of salivary and lacrimal systems made easy: a simplified technique. PMID- 1408244 TI - Coccidioidomycosis of the external ear. PMID- 1408245 TI - Hearing threshold differences and risk of acoustic tumor. PMID- 1408246 TI - Hearing threshold differences and risk of acoustic tumor. PMID- 1408247 TI - Role of audiology in identification of acoustic tumors. PMID- 1408248 TI - Reacting to Act 6. PMID- 1408249 TI - The challenge ahead. Interview by Maria T. Montesano. PMID- 1408250 TI - Canadian physicians debate reform and repairs to an eroding system. PMID- 1408251 TI - The French national health care system--some perspectives. PMID- 1408252 TI - Discussing the issues with the senatorial candidates. PMID- 1408253 TI - First public release of physician-specific data by council is imminent. PMID- 1408254 TI - Hahnemann's "Point of Light". PMID- 1408256 TI - Tuberculosis spectre haunts public health. PMID- 1408255 TI - Monitoring impaired physicians: a tool for relapse prevention. AB - Physicians experience a broad spectrum of health problems which can disrupt their personal lives and impair their ability to function professionally. Some of these illnesses--such as alcoholism and other drug dependency, and certain psychiatric disorders--are chronic. While treatment usually results in remission of active symptoms, there is a risk of relapse if necessary steps are not followed. Therefore, the key to continued recovery and stable functioning lies in effective relapse prevention. PMID- 1408257 TI - KePRO's community outreach programs. AB - The Keystone Peer Review Organization board of directors and management have always taken pride in knowing that individually and as a group they have put forth extra effort to assure maximum efficiency and fairness in the review system. Another source of pride to the organization is our Community Outreach Program which we think is one of the finest and most progressive in the country. While such a program is required under our contract with the Health Care Financing Administration (HCFA), we saw the need to go beyond the HCFA requirements. PMID- 1408258 TI - PA AIDS ETC offering HIV clinical training. PMID- 1408259 TI - Who's setting your priorities? PMID- 1408261 TI - Health views from the House. Interview by Maria T. Montesano. PMID- 1408260 TI - Medical ethics and maternal-fetal conflicts. AB - As ethical issues are raised by more and more aspects of medical practice, medical ethics becomes an ever more complex and confusing enterprise, presenting yet another physician dilemma. This article offers guidelines for individual physicians and hospital ethics committees in dealing with medical ethics and maternal-fetal conflicts. PMID- 1408262 TI - PennDOT publishes amendments to licensing regulations. PMID- 1408264 TI - Medicare conversion factor split for 1993. PMID- 1408263 TI - Clarifying concurrent care. AB - Pennsylvania Blue Shield's concurrent care policy for both the Medicare program and its private business is the source of much confusion and exasperation among physicians, especially with regard to medical-medical concurrent care. This article seeks to clarify the process for better understanding by physicians. PMID- 1408265 TI - Blue Shield, society answer RBRVS questions. PMID- 1408266 TI - Possible changes in store for PRO program. AB - Some drastic changes in the peer review organization (PRO) program have been proposed by the Health Care Financing Administration in recent months. Some of them are good, but, as we see them, some could cause problems for PROs, hospitals, and physicians. PMID- 1408267 TI - AIDS: startling statistics call for strong actions. PMID- 1408268 TI - Legacy and future. PMID- 1408269 TI - Understanding durable powers of attorney. AB - Many physicians will encounter the use of durable powers of attorney in their medical practices as patients become more informed and more prepared for end-of life decisions. Be aware, however, that these documents vary in the authority they grant the holder, and that they differ significantly from living wills. PMID- 1408270 TI - HCFA takes on "hassle factor". PMID- 1408271 TI - HCFA and the political scene. AB - Will the fact that this is a presidential election year affect the philosophy and direction of the Health Care Financing Administration as it relates to health care financing in general and the peer review organization program in particular? Perhaps. PMID- 1408272 TI - Developing a patient communications plan. The Health Care Group. PMID- 1408273 TI - A courtroom lesson in physician-assisted suicide. AB - Physician participation in euthanasia and assisted suicide has been the subject of long-standing debate and is unlikely to be resolved easily or soon. The Pennsylvania Medical Society's Medical Student Section explored this topic recently in a second "mock trial" held in conjunction with the Temple University School of Law and co-sponsored by the Pennsylvania Medical Society Liability Insurance Company. This is an account and essay from that trial. PMID- 1408274 TI - Standards of review. PMID- 1408275 TI - Musings on mentoring. PMID- 1408276 TI - Senatorial candidates respond. Federal role in health care/basic services. PMID- 1408277 TI - Senatorial candidates respond. Federal role in health care. PMID- 1408278 TI - Preventive law monthly. Are you legally healthy? PMID- 1408279 TI - Solving the day care puzzle: how to choose the safest center for your child. PMID- 1408280 TI - TB revisited! PMID- 1408281 TI - Statement on HIV/HBV/AIDS disease and nursing students. PMID- 1408282 TI - Advanced licensure: personal plum or public shield? PMID- 1408283 TI - [Personal memories of personally experienced pediatrics (1946-1991)]. AB - As a kind of farewell speech about my pediatric activity some personal experiences are described, which are of special interest for me and perhaps of a certain historic interest for the reader. The occurrences derives from my profession at the University-Clinics of Pediatrics in Vienna, Bern, Basel and Innsbruck. PMID- 1408284 TI - [Organization of the psychotherapy-psychosomatic department and its integration into the University Pediatric Clinic]. AB - With regard to the 20 years history of our psychotherapeutic unit some essential feed-back-loops between medical pediatric work and our systemic thinking are presented. So-called objective tasks interfere with group dynamics and subjective task formulations. If two models (the biomedical and the systemic-therapeutic) collide, both of them get "contaminated" and should be changed in a co-evolutive process--for the sake of the patients and their families. In our experience this is only possible, if autonomy of the unit is present, then the unit can wait for "perturbations". PMID- 1408285 TI - [Bronchial asthma and systematic family therapy: treatment concept, initial contact and therapy follow-up]. AB - Psychosocial factors play an important role in pathogenesis and maintenance of bronchial asthma. However, besides conventional treatment family therapy seems to be less applied. A treatment plan for the integration of systemic family therapy into pediatric management of asthma has been developed and validated. Its special feature is an invariant family treatment offer after the initial session, with the decision of acceptance or rejection upon the family. The main focuses of family therapy are coping and family interaction, thus indirectly influencing the course of illness. Up to now 66 family sessions have been conducted with 11 families; five families agreed to the first session only. In a mean observation time of two years after the end of family therapy we found a drastic reduction in hospital readmissions of the asthmatic patients, even in the patients of families who took part in the initial session only. This may indicate a better control of asthma symptoms in patients and families. Family therapy is suggested as a valuable and additional tool in treatment of asthmatic children, irrespectively of their allergic status. PMID- 1408286 TI - [The painful hip joint in the child: differential diagnosis and therapy of coxitis fugax, Perthes disease and septic coxitis]. AB - The differential diagnosis of a painful hip joint in children is important. Transient synovitis is frequently seen in children from 3 to 7 years of age with a short history of limping. The joint effusion is visualized by ultrasound. Radiograms and laboratory data are negative. Therapy consists of short term bed rest supported by an oral antiphlogistic drug. Children with Legg-Calve-Perthes disease complain about knee or hip pain in an early stage. X-ray documentation in the a.p and axial view are mandatory as well as ultrasound visualization of the accompanying effusion. Healing of the capital femural epiphysis is aided by weight relief and improved head containment. This may need from one to three years according to the age of the child and the amount of head involvement. More than half of the children's hips with Perthes disease surgical help to achieve a satisfactory result. Hip pain is overwhelming in cases of septic arthritis of the hip joint. This is the most important help to differentiate septic coxitis from transient synovitis or Perthes disease. Rapidly rising values of red cell sedimentation and c-reactive protein are important for early diagnosis. Septic effusions are visualized by ultrasound. X-ray changes are absent in the beginning and are seen only in delayed cases. Early arthrotomy with scrupulous rinsing of the joint, followed by parenteral antibiotic treatment, is the treatment of choice. PMID- 1408287 TI - Cerebral infarction in a child. A case report. AB - Cerebral infarcts in children are rather rare and in most cases no precise etiology is established. The authors describe a case of cryptogenetic cerebral infarction in a 9-year-old boy. The child presented an acute onset of hemiplegia in the right arm and leg, central facial palsy, dysarthria and steppage. The infarction was proved by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Laboratory and instrumental studies rule out all known causes of brain infarction. The only possible etiopathogenetic hypothesis was a varicella arteritis which occurred 45 days before the clinical manifestation. PMID- 1408288 TI - [Familial Mediterranean fever--a case report]. AB - A case of a ten years old boy with recurrent fever and abdominal pain starting at the age of five years is reported. Later the attacks were accompanied by chest pain. There were only indifferent changes in laboratory examination. Neither a wide range of antibiotics, nor appendectomy and tonsillectomy prevented the boys symptoms. The diagnose was established after five years by a positive Metaraminol test, that precipitated a disease-like attack. The therapeutic use of colchicine salicylate reduced the severity and frequency of attacks in out patient. In agreement with other authors it should be emphasized, that in general the benefit of colchicine outweighs possible side effects of a long term therapy also in children. PMID- 1408289 TI - [Stress and susceptibility to infection]. AB - The influence of various stressors upon the human immune system, was and presently is the subject of many clinically oriented as well as experimental studies. Even though it is not always clear how relevant the reported observations are in behalf to the beginning, the course and the outcome of infectious, neoplastic and autoimmune diseases, there is hardly any doubt, that stress may influence multiple aspects of the immune answer. The sensitivity of the immune system to stress factors is not merely fortuitous, but is an indirect consequence of the regulatory reciprocal influences between the immune system and the central nervous system. These interconnections seem to represent building blocks of a long-loop regulatory feedback-system, which plays an important role in the coordination of stressors and psychological influences upon the course of infections and inflammatory diseases. PMID- 1408290 TI - [From psychobiological stress research to neuropsychoimmunology]. AB - Psychoimmunology--a neologism--is a short term for the growing evidence that there are multiple interactions between central nervous system, vegetative nervous system, endocrinological system and immunological system. In the history of research the psychobiological stress concept of Hans Selye has been the most powerful basis for the ongoing empirical work in investigating aspects of systemic processes of psychoimmunology. Nowadays there is no doubt that the immunological system must not be seen as an independently functioning organic system. Simple causal links (like stressor-strain-relations) are not useful in explaining the complex interactions that we observe when biological phenomena simultaneously are taken into consideration. Especially with psychological stressors--the most frequent kind of troubles in our contemporary way of life--we have to stress the importance of the individual's evaluation of potentially stressful situations. In a wide variety a stressor becomes the potential of provoking strain because of my own appraisal. This multiple-step-process of appraisal is dependent on my coping abilities and coping strategies regarding an objectively or subjectively dangerous situation. Although there are common genetic and predispositional factors influencing the stress reaction we have to focus more on psychological phenomena, especially the possibility of conditioning stress reactions. As we know by empirical data some reactions of the immunological system are also influenced by learning processes like classical conditioning procedures. This knowledge may be used for a better understanding of a lot of chemical findings. PMID- 1408291 TI - [Liposomal amphotericin B in the treatment of candida infection in a 3-month-old infant]. AB - Amphotericin B (Amph-B) is the treatment of choice for systemic fungal infections. The application of high doses is limited due to the high incidence of acute side effects (fever, chills) and organ toxicity (reduction in glomerular filtration rate, renal tubular damage). Amph-B was applied without success in a three months old infant, who suffered from systemic candidiasis. After a change to high doses (3-5 mg/kg/day) of liposomal Amph-B (Amph-lip) rapid improvement of the patient's condition occurred and the pulmonary lesions disappeared during six weeks of treatment (total dose 185.5 mg/kg). Acute side effects or renal function abnormalities did not occur. The reported case indicates that the application of high doses of Amph-lip is an alternative to conventional Amph-B in treatment of systemic fungal infections. PMID- 1408292 TI - Pain: paradigms and treatments. PMID- 1408293 TI - Chronic epidural bupivacaine-opioid infusion in intractable cancer pain. AB - This study examined the efficacy and toxicity associated with chronic epidural opioid-bupivacaine infusions. In a series of 68 patients with cancer pain refractory to epidural opioids alone, analgesia was effectively regained by infusing a opioid-bupivacaine combination. Sixty-one patients (90%) were considered treatment successes, according to conventional criteria. Median length of therapy was 60-120 days, with the longest infusion lasting 277 days. Chronic bupivacaine infusion concentrations ranged from 0.1 to 0.5% with infusion rates varying from 4 to 18 ml/h. The majority of patients experienced pain relief with little or no sympathetic or sensorimotor impairment after the first 24 h at bupivacaine concentrations of 0.125-0.25% and were managed in home or chronic care settings without the need for re-hospitalization. In patients receiving higher bupivacaine concentrations, sympathetic, sensory and motor blockade were well tolerated during chronic infusion. Sensory loss was consistently observed only at bupivacaine concentrations exceeding 0.25%, and motor impairment occurred only at concentrations exceeding 0.35%. Postural hypotension was observed in 6 patients (9%) for the first 24 h only, which supports the requirement for monitoring and fluid therapy during initiation of the bupivacaine infusion. No patient experienced CNS or systemic toxicity, despite plasma total bupivacaine concentrations as high as 10.8 micrograms/ml. Serial plasma bupivacaine levels were measured in 15 patients during chronic infusion. There was considerable inter- and intra-individual variability in plasma bupivacaine concentrations and bupivacaine clearance. We conclude that epidural opioid-bupivacaine infusion is an effective and safe technique for long-term administration of analgesics in the refractory cancer patient. PMID- 1408294 TI - Patient-controlled analgesic infusions: alfentanil versus morphine. AB - Previously, we found that cancer patients using a pharmacokinetically based patient-controlled intravenous infusion system (PKPCA) to regulate their own morphine infusion rates achieved more relief from oral mucositis pain than similar patients using morphine by bolus-dose PCA. In this study, we employed the PKPCA system to compare efficacy and side-effect intensities of 2 mu-selective opioid analgesics, alfentanil and morphine, in bone marrow transplant (BMT) patients self-administering the drugs to relieve pain from oral mucositis. Patients using morphine by PKPCA obtained more pain relief than patients regulating their own alfentanil infusions during the first 4 days of continuous opioid infusion therapy. Side-effect intensities did not differ between the 2 study groups. In contrast to patients using morphine for 4-14 days, those receiving alfentanil by PKPCA required unexpectedly high plasma concentrations of the drug to obtain equivalent pain relief. Our results indicate that either the relative potencies of these 2 mu-selective opioids differ from previous estimates or analgesic tolerance developed to alfentanil but not to morphine. We conclude that alfentanil has similar efficacy in control of prolonged pain in BMT patients, but the utility of alfentanil in long-term pain management may be limited by relatively rapid tolerance onset. PMID- 1408295 TI - Circadian distribution of extra doses of narcotic analgesics in patients with cancer pain: a preliminary report. AB - In this open study we reviewed the circadian distribution of extra doses of narcotic analgesics in 61 bed-ridden patients with cancer pain. The information was collected prospectively and retrospectively in 34 and 27 cases, respectively. All patients were receiving parenteral narcotics using the Edmonton Injector, and none had incidental pain or cognitive impairment. A total of 1322 extra doses of narcotics (each dose = 10% of the daily dose) were administered during 610 patient days (average of 2.17 +/- 1.6 doses/patient/day). The mean daily number of extra doses during each interval was as follows: 02.00-06.00 h (0.24 +/- 0.27), 06.00-10.00 h (0.26 +/- 0.31), 10.00-14.00 h (0.43 +/- 0.44), 14.00-18.00 h (0.44 +/- 0.41), 18.00-22.00 h (0.40 +/- 0.36), and 22.00-02.00 h (0.40 +/- 0.36) (02.00-06.00 h and 06.00-10.00 h vs. 10.00-02.00 h: P less than 0.01). Forty-five of 61 patients (76%) received most of their extra doses of narcotics between 10.00 and 22.00 h. The data suggest that our patients require a larger number of extra doses during day time. Our design cannot establish the reason for this circadian variation. PMID- 1408296 TI - Cervicogenic headache: anesthetic blockades of cervical nerves (C2-C5) and facet joint (C2/C3). AB - In a series of 14 patients with cervicogenic headache, cervical nerve blockades (C2-C5 and facet joint C2/C3) have been carried out in order to elucidate possible underlying mechanisms and to evaluate the diagnostic potential of these procedures. Blockade of the C2 nerve resulted in freedom from pain in 5 of 10 patients and seemed to be the most informative procedure. Two patients out of 9 reported freedom from pain following C2/C3 facet joint injection. No patients experienced complete pain relief following C3, C4 or C5 blockades. C4 and C5 nerve blockades are probably of little value in the work-up of such patients. When evaluating the C2/C3 facet joint injection, one has to take possible leakage of anesthetic agent from the joint into consideration, since the third occipital nerve which runs close to the facet joint may be anesthetized through the leakage. PMID- 1408297 TI - The efficacy and efficiency of a self-administered treatment for adolescent migraine. AB - Migraine headaches are frequent in adolescents. Although many adolescents are adequately treated palliatively with analgesics, an important subgroup requires prophylactic treatment. Medical treatments for adolescents with frequent severe headaches is often problematic. Prophylactic pharmacological treatments are often shunned by adolescents and their parents because of concern over drug usage. Moreover, propranolol, the most widely used prophylactic drug with adults, is frequently not effective. Psychological interventions are effective but are costly and often not available. A randomized controlled trial was undertaken to evaluate the efficacy and efficiency of a predominantly self-administered treatment that could be delivered in a very cost-efficient format. Eighty seven adolescents (63 females and 24 males) ranging in age from 11 to 18 years were randomly assigned to receive a self-administered treatment, the same treatment delivered by a therapist or a control treatment. Self-administered and clinic treatment were equally effective and superior to the control treatment. However, the self-administered treatment was substantially more efficient. Both active treatments were durable at 1-year follow-up. PMID- 1408298 TI - Facet joint injection and facet nerve block: a randomised comparison in 86 patients with chronic low back pain. AB - Eighty-six patients with refractory chronic low back pain were randomly assigned to receive either facet joint injection or facet nerve block, using local anaesthetic and steroid. There was no significant difference in the immediate response. The duration of response after facet joint injection was marginally longer than after facet nerve block (P less than 0.05 1 month after infiltration), but for both groups the response was usually short-lived; by 3 months only 2 patients continued to report complete pain relief. Patients who had complained of pain for more than 7 years were more likely to report good or excellent pain relief than those with a shorter history (P less than 0.005), but no other clinical feature was of value in predicting the response to infiltration. Facet joint injections and facet nerve blocks may be of equal value as diagnostic tests, but neither is a satisfactory treatment for chronic back pain. PMID- 1408299 TI - The effectiveness of psychological interventions for the rehabilitation of low back pain: a randomized controlled trial evaluation. AB - Forty-five low back pain patients were randomly assigned to either a standard inpatient rehabilitation program or the standard program with additional psychological components. The standard program emphasized education, support, and physical reconditioning through exercise. Patients receiving the psychological program were given additional training in relaxation and other coping skills and received contingent reinforcement for exercise. Both programs included reduction of medication intake and an emphasis on family involvement after discharge. Measures of functional status were taken prior to the program, at discharge from the 3-week inpatient program, and at a 6-month follow-up appointment. These data revealed that patients improved their overall functioning at discharge and maintained these gains at the follow-up assessment. A similar pattern of findings was obtained for self-reported pain and interference. Furthermore, 81% of the patients had returned to work or were engaged in active job retraining by the follow-up. Using a conservative measure of full-time return to the same or an equivalent job, 57% were employed by the follow-up. Patient improvement, however, was not differentially affected by treatment group assignment, suggesting that the psychological treatment failed to add to the effectiveness obtained by the standard rehabilitation program. Results are discussed in the context of improving patient outcomes from rehabilitation for low back pain. PMID- 1408300 TI - Psychological aspects of reflex sympathetic dystrophy: a review of the adult and paediatric literature. AB - In 1864, W. Mitchell and colleagues first described the clinical syndrome which came to be known as 'causalgia'. Since that time, the concept of sympathetically related pain has evolved. There is general agreement that profound emotional and behavioural changes can follow these types of pain. Opinions have varied widely on the issue of a psychological etiology. It has often been suggested that certain personality traits predispose one to develop sympathetically related pain syndromes. A review of the literature reveals no valid evidence to substantiate this claim. PMID- 1408301 TI - The effect of experimental muscle pain on the background electrical brain activity. AB - The purpose of this project was to investigate whether specific effects in the background activity of the brain associated with the experience of pain can be depicted by means of quantitative electroencephalography (EEG). Lasting pain was induced by intramuscular infusion of hypertonic saline. The infusion was titrated to maintain pain for a sufficient time to obtain enough data for meaningful analysis. In a first study on 12 subjects, using a single, blind, repeated measures design with randomization of the administration of isotonic (0.9%) and hypertonic (5%) saline, and with subjects unaware of the fact that one substance was isotonic saline, a statistically significant pain response could be attributed to the administration of hypertonic saline. In a second study on 19 subjects, again using a randomized repeated measures design, topographic EEG measures were examined with respect to experimentally induced pain and pain from memory. Prior to each of these experimental stages, baseline recordings were obtained to satisfy the requirement of the crossover design. In addition to the common frequency bands used in EEG, we also obtained data in the frequency range of 35-100 Hz. The short-term variability of the selected EEG measures and their suitability as a sample estimate were assessed by computing the coefficient of variation from all selected epochs of a given subject at baseline. When compared to baseline, spectral analyzed EEG measures during experimental pain demonstrated statistically significant increases in the beta and 35-100 Hz frequency ranges, most notably at the temporal recording sites. There was no statistically significant difference between the EEG measures for (1) experimental pain vs. pain from memory, and (2) the 2 baseline recordings. The great variability in the topographical aspect of the between-subject response was interpreted as being strongly suggestive of the contamination of EEG measures by phenomena attributed to the jaw, facial and scalp musculature. In fact, Pearson correlation coefficients, as high as 0.92, were found between measures in the frequency band of 35-100 Hz and the beta frequency range. The unexplained variance in the heightened beta cortical power density can be attributed to the vigilance scanning of pain processes. Due to the fact that the statistically significant effect of pain on the topographic EEG measures were not different from imagined pain, we concluded that these effects are non-specific for pain. PMID- 1408302 TI - Cerebrospinal fluid kinetics of epidural clonidine in man. AB - Ten patients with deafferentation pain after spinal cord injury were given 150 micrograms clonidine epidurally. CSF and plasma samples were collected over the following 24 h, and drug concentrations were measured by radio-immunoassay. The results of only 6 patients are included in the pharmacokinetic analysis because the catheters were not in the epidural space in the remaining 4 patients. These analyses revealed a mean maximum CSF concentration of 228 ng/ml whereas the mean plasma concentration at all time points was less than 0.7 ng/ml. The elimination half-life of epidural clonidine was 66 +/- 2 min, while the absorption half-life was 31 +/- 7 min, Tmax was 60 +/- 7 min and Cmax was 228 +/- 56 ng/ml. The ratio of the area under the curve (AUC) for CSF and plasma was 52. One patient's catheter was intrathecal and 3 were not in the epidural space. The measured plasma concentrations were similar after all injections. As 4 of 6 patients with epidural catheters obtained pain relief and all 3 patients with spasms obtained relief from epidural clonidine, these data suggest that clonidine has a place in the treatment of patients with spinal cord injury. PMID- 1408303 TI - CT contrast evidence of injectate encapsulation after long-term epidural administration. AB - This case report provides radiographic evidence (CT scan with Iopamidol) to support the development of epidural injectate encapsulation in response to long term epidural morphine injections via an implanted polyurethane catheter. The patient complained of intense low interscapular pain when the catheter was used for administration of epidural morphine for control of angina. The patient had previously enjoyed 3 months of excellent pain relief following the initiation of epidural morphine via an implanted portal device. The CT scan, with contrast dye injected via the epidural catheter, clearly showed loculation of the injectate and associated indentation of the spinal cord. It is significant to note that the dye in the encapsulated sheath occupied a significant proportion of the spinal canal extending from T7 to T9. PMID- 1408304 TI - Viscerosomatic convergence onto feline spinal neurons from esophagus, heart and somatic fields: effects of inflammation. AB - One objective of this study was to examine a mechanism for the inability of patients to distinguish esophageal pain from cardiac pain. Patients with esophageal disease and angina pectoris often perceive pain as originating from the same somatic fields. Another objective was to compare the effect of esophageal distension between animals with a non-inflamed or with an inflamed esophagus. For this study in anesthetized cats, we recorded extracellular action potentials from T2-T7 spinal neurons that responded to intraluminal distension of an untreated or a turpentine-inflamed distal esophagus. Threshold distension volumes were compared between these 2 groups of animals. Neurons also were examined for effects of intracardiac bradykinin injection and somatic stimuli. Results showed that spinal neurons responded to a smaller threshold distension volume when cells in animals with an inflamed distal esophagus were compared to cells in animals with a non-inflamed distal esophagus. Spinal neurons that received input from the distal esophagus also received convergent input from the heart and somatic fields. Our data supported the hypotheses that (1) referred pain from the distal esophagus resulted from activation of the same spinal neurons by visceral and somatic input, (2) pain originating from the distal esophagus and heart might be difficult to distinguish because of viscerosomatic and viscerovisceral convergence onto the same spinal neurons, and (3) an inflamed distal esophagus might be more sensitive to distension than a non-inflamed esophagus. PMID- 1408305 TI - Fos-like proteins in the lumbosacral spinal cord following noxious and non noxious colorectal distention in the rat. AB - The rat lumbosacral spinal cord was immunocytochemically stained for Fos-like immunoreactivity following repetitive colorectal distention (CRD) to 20, 40 or 80 mm Hg. Following all 3 distention pressures, Fos-like immunoreactive (Fos-ir) nuclei were observed primarily in laminae I-II, V-VII and X, although some labeled nuclei were observed in laminae III-IV. Eighty mm Hg CRD resulted in significantly more Fos-ir nuclei than 20 or 40 mm Hg CRD. Morphological examination of the colon revealed clear signs of inflammation following 80 but not 20 mm Hg CRD. Acute 20 mm Hg CRD is a non-noxious stimulus, suggesting that both noxious and non-noxious visceral stimuli can induce Fos-like immunoreactivity in the spinal cord. It is suggested that activation of neuropeptide-containing small-diameter primary afferents is necessary, although not necessarily sufficient, to induce c-fos in the rat spinal cord. PMID- 1408306 TI - Differential influence of naloxone on the responses of nociceptive neurons in the superficial versus the deeper dorsal horn of the medulla in the rat. AB - Naloxone (200 micrograms/kg, i.v.) reduced the noxious thermal stimuli-evoked responses of 16/25 nociceptive neurons in the superficial laminae whereas it enhanced the responses of 6/10 nociceptive neurons in the deeper dorsal horn. However, a different picture emerged when selectivity of neuronal responsivity (nocireceptive or multireceptive) was considered. In the superficial dorsal horn, naloxone reduced the responses of the majority of (15/18) selectively nocireceptive neurons. The reduction in responses became apparent within 60 sec following naloxone administration and returned to control level within 48 min. In contrast, the responses of the majority of multireceptive neurons in the superficial (6/7), or the deeper (6/10) dorsal horn, were enhanced. The excitatory action in the superficial dorsal horn persisted for only 6-15 min, whereas it persisted for 40-70 min in the deeper dorsal horn. The firing of the majority of cold-receptive neurons (6/8) in the superficial dorsal horn was not altered. These effects were stereoselective since (+)-naloxone, the inactive isomer of naloxone, did not affect the responses of 14/16 nociceptive neurons. It is concluded that naloxone differentially, and selectively, affects the firing of nociceptive neurons in the superficial versus the deeper dorsal horn, and the firing of selectively nocireceptive versus multireceptive neurons. The relevance of these findings to the behavioral effects of naloxone, hyperalgesia and analgesia, is discussed. PMID- 1408307 TI - Differential antinociceptive effects of morphine and methylmorphine in the formalin test. AB - The antinociceptive activities of morphine, and its quaternary analogue methylmorphine, have been compared after intraperitoneal and intracerebroventricular administrations in the mouse paw formalin test. Systemic morphine inhibited both the early and late phases of the formalin-induced licking response and this activity was naloxone sensitive. In contrast, systemic methylmorphine inhibited only the late phase, and this activity was blocked by pre-treatment with methylnaloxone. Central administration of either morphine or methylmorphine inhibited the early phase of the licking response partially and the late phase completely. Systemic naloxone inhibited the central action of both opioids, whilst systemic methylnaloxone did not affect the central action of methylmorphine. The results indicate that the early phase of the response to formalin in the mouse may be inhibited by stimulation of central opioid receptors whilst inhibition of the late phase may involve both peripheral and central opioid receptors. PMID- 1408308 TI - When a 'significant' correlation and a 'non-significant' correlation are not significantly different. PMID- 1408309 TI - Grading the severity of chronic pain. AB - This research develops and evaluates a simple method of grading the severity of chronic pain for use in general population surveys and studies of primary care pain patients. Measures of pain intensity, disability, persistence and recency of onset were tested for their ability to grade chronic pain severity in a longitudinal study of primary care back pain (n = 1213), headache (n = 779) and temporomandibular disorder pain (n = 397) patients. A Guttman scale analysis showed that pain intensity and disability measures formed a reliable hierarchical scale. Pain intensity measures appeared to scale the lower range of global severity while disability measures appeared to scale the upper range of global severity. Recency of onset and days in pain in the prior 6 months did not scale with pain intensity or disability. Using simple scoring rules, pain severity was graded into 4 hierarchical classes: Grade I, low disability--low intensity; Grade II, low disability--high intensity; Grade III, high disability--moderately limiting; and Grade IV, high disability--severely limiting. For each pain site, Chronic Pain Grade measured at baseline showed a highly statistically significant and monotonically increasing relationship with unemployment rate, pain-related functional limitations, depression, fair to poor self-rated health, frequent use of opioid analgesics, and frequent pain-related doctor visits both at baseline and at 1-year follow-up. Days in Pain was related to these variables, but not as strongly as Chronic Pain Grade. Recent onset cases (first onset within the prior 3 months) did not show differences in psychological and behavioral dysfunction when compared to persons with less recent onset. Using longitudinal data from a population-based study (n = 803), Chronic Pain Grade at baseline predicted the presence of pain in the prior 2 weeks. Chronic Pain Grade and pain-related functional limitations at 3-year follow-up. Grading chronic pain as a function of pain intensity and pain-related disability may be useful when a brief ordinal measure of global pain severity is required. Pain persistence, measured by days in pain in a fixed time period, provides useful additional information. PMID- 1408310 TI - Predictive factors in advanced cancer pain treated only by analgesics. AB - Analgesic response, incidental pain and pain mechanism were evaluated in order to predict the chances of pain relief in advanced cancer patients. In an observation period of about 2 months, 130 patients were followed at home until death using only a pharmacological approach to control pain according to the WHO ladders. Ninety-eight patients were considered. Pain relief was considered good if less than moderate. Pain was assessed during the course of examinations (2-3 a week) by independent observers. If other techniques were needed the result was considered negative. The patients were tested with an NSAID (Diclofenac) and assigned to group 1 if the pain became slight in 3 days. If the response was negative, a 4-day trial with opioids was started. If the pain was slight the patient was included in group 3, otherwise in group 5. Every patient belonging to these groups but with incidentical pain was included in groups 2, 4 and 6, respectively. For each group a subdivision was made according to the pain characteristics. There was a progressive worsening in pain relief in groups 4, 5 and 6, suggesting a good correlation between response to the drugs and future chances of pain control in a period of 2 months. This study demonstrates that incidental pain reduces the possibility of pain control (50%) with the exclusive administration of analgesics in patients with a mean life expectation of about 2 months. This negative influence is counterbalanced by the possible individual response to analgesics administered sequentially during a 1-week period (85.8% good pain relief with NSAID, 74% with opioids).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408311 TI - Validity of the Sickness Impact Profile Roland scale as a measure of dysfunction in chronic pain patients. AB - This study examined the reliability and validity of the Roland scale (taken from the Sickness Impact Profile: SIP) as a measure of dysfunction among chronic pain patients. One hundred forty-four subjects completed the SIP when they were screened for admission to an inpatient pain management program. One hundred sixteen subjects were subsequently re-administered the SIP at admission to inpatient treatment. A 3-month post-treatment administration of the SIP was performed for 52 of these subjects. Roland scale scores were calculated from the SIP for each patient. Test-retest stability coefficients indicated that the SIP Roland scale was generally as reliable as the SIP Total, Physical, and Psychosocial scale scores. Consistent with previous research, correlational analyses indicated that the SIP Roland scale is strongly associated with the SIP Physical but not the SIP Psychosocial scale. The SIP Roland scale and the other SIP scales demonstrated similar sensitivity to changes associated with multidisciplinary inpatient treatment for chronic pain. Finally, the pattern of relationships between the SIP Roland scale and several pain-related measures supported the concurrent validity of the SIP Roland scale. The results of the analyses were very similar for patients presenting with and without low back pain. The study supports the reliability and validity of the SIP Roland scale items for assessing dysfunction of chronic pain patients with pain in sites other than the low back as well as those with low back pain. PMID- 1408312 TI - Does a regional nerve block change cutaneous perception thresholds outside the anaesthetic area? Implications for the interpretation of diagnostic blocks. AB - The present study was performed on pain-free subjects and patients to analyse if local anaesthetics (LA) normally used for nerve blocks in the orofacial region resulted in generalised changes in cutaneous somatosensory perception thresholds outside the territory of the primarily blocked nerve. Five subjects received an intra-oral nerve block and 5 patients received epidural anaesthesia, serving as a reference group considering the larger amounts of LA used in this latter type of anaesthesia. No differences (after vs. prior to LA) were detected regarding thresholds to tactile, cold, warmth or heat pain stimuli in skin areas outside the regions directly blocked. This was also true for the difference limens between warm-cold thresholds. Our data do not indicate any generalised influence on tactile, thermal and pain perception thresholds in pain-free subjects. PMID- 1408313 TI - The role of ischaemia in the analgesia which follows Bier's block technique. AB - The effect of 30-min tourniquet ischaemia (Bier's block) on the antidromic homolateral left median nerve sensory potential (SP) and on the bilateral sympathetic skin response (SSR) was studied in 6 healthy volunteers. The SSR was provoked both acoustically and by electrical stimulation of the median nerve; the latter stimulus was also used to provoke the SP. After 28 min of tourniquet ischaemia, the electrical stimulus failed to provoke the SP and bilateral SSR, indicating blockade of the afferent limb of the reflex. The acoustic SSR was unaffected by ischaemia, and thus the efferent limb of the SSR was not blocked, indicating that ischaemia does not affect the post-ganglionic efferent C fibres. These findings confirm that 30 min of ischaemia blocks A beta afferent fibres but does not block efferent C fibres. Thus the analgesia following Bier's block alone, in some patients with sympathetically maintained pain, most likely results from the ischaemic blockade of sensory A beta fibres, confirmed both acoustically and by electrical stimulation of the median nerve. PMID- 1408314 TI - Chronic back pain, acute postoperative pain and the activation of diffuse noxious inhibitory controls (DNIC). AB - The effect of the presence of either chronic or acute clinical pain on pain threshold and on the nociceptive flexion reflex (RIII) threshold was studied. The experimental pain sensation and the flexion reflex were evoked by trains of short electrical pulses. It was hypothesized that both kinds of clinical pain would be able to induce 'diffuse noxious inhibitory controls' (DNIC) and thereby raise the 2 experimental thresholds. Patients with chronic low back pain, patients with postoperative pain from oral surgery, and pain-free subjects were tested in 3 conditions: during baseline, after i.v. administration of a placebo, and after i.v. administration of naloxone. In comparison with 2 pain-free control groups, the 2 pain groups had a significantly higher pain threshold in all conditions. However, the RIII threshold was not significantly elevated in chronic or acute pain patients compared to controls. Naloxone had no effect on the RIII or pain threshold in any of the groups. It is concluded that the increased pain threshold which is frequently found in chronic pain patients, and which could be confirmed in the present study, does not result from a DNIC effect. The adaptation level theory offers an alternative explanation. Also, the acute postoperative pain in this study did not seem to induce DNIC. Because other forms of acute pain have been found to be effective in activating DNIC, future research should establish which pains are and which pains are not effective. PMID- 1408315 TI - Symptoms of impairment, disability and handicap in low back pain: a taxonomy. AB - The functional consequences on everyday living which result from chronic low back pain commonly require services which are difficult to access. This deficiency in meeting the needs of these patients is partially explained by inadequacies in clinical assessment. Medical evaluation may be exhaustive, but frequently the assessment of physical and psycho-social dysfunction at the personal and family level is inadequate. In low back pain, as with most chronic ailments, there is no agreed-upon taxonomy of the functional consequences of the disorder upon which to establish a comprehensive clinical appraisal. In this paper a taxonomy is presented for the impairments, disabilities and handicaps which result from chronic low back pain. The taxonomy has been based on data from a survey of 74 individuals with low back pain and is structured generally according to the International Classification of Impairments, Disabilities and Handicaps (WHO 1980). The taxonomy is proposed as a conceptual framework and vocabulary for both clinical practice and research. The taxonomy is not a measurement instrument nor does it indicate the frequency of occurrence of disabilities. A classification is basic to the advancement of scientific understanding, and usage of a standard vocabulary such as this plays an important role in establishing a responsive health service capable of meeting the needs of the population with chronic low back pain. PMID- 1408316 TI - Spatial summation in human thermal pain perception: comparison within and between dermatomes. AB - Spatial summation of thermal pain has recently been reported when stimulus presentations were restricted within a single dermatome. The present study examined whether the magnitude of spatial summation of human thermal pain perception would vary when stimuli were presented within vs. between adjacent dermatomes. Noxious contact heat stimuli from 43 degrees C to 51 degrees C (5 sec duration) were applied to the forearm using areas of 0.21-2.10 cm2. Subjects rated the intensity and unpleasantness of pain using visual analog scales. For stimuli from 45 degrees C to 51 degrees C, there was a significant increase in ratings with increasing stimulus area for both intensity and unpleasantness. When two thermodes were used simultaneously in adjacent dermatomes, the ratings did not differ significantly from those for the same stimulus area in a single dermatome. We conclude that spatial summation both within and between dermatomes plays a significant role in thermal pain perception across the range from threshold to tolerance. PMID- 1408317 TI - Akathisia after long-term epidural use of droperidol: a case report. AB - Droperidol has both anti-emetic and neuroleptic properties and its epidural administration has been reported (Naji et al. 1990). Its side effects when administered via this route are not known. We report a case of long-term (2 months) epidural administration of droperidol to a cancer patient who was receiving epidural morphine and who manifested nausea and vomiting. Akathisia developed progressively and subsided 72 h after droperidol was discontinued. PMID- 1408318 TI - Treatment of inflammatory, neuropathic and sympathetically maintained pain in a patient with Sjogren's syndrome. AB - We present a case of Sjogren's syndrome with a painful peripheral neuropathy where pain control required both anti-inflammatory and sympatholytic treatments. This case suggests that the pain in some inflammatory disorders with nerve injury may have a component mediated by an alpha adrenergic receptor. PMID- 1408319 TI - Self-mutilation following brachial plexus injury sustained at birth. AB - Self-mutilation after deafferentation injuries has been reported only rarely in adult humans. This behavior has been found to be similar to that observed in animals that have been subjected to experimental deafferentation. We present a child with a brachial plexus injury sustained at birth who began to bite her analgesic digits. Self-mutilation behavior in humans is reviewed and its relevance to current deafferentation pain animal models is examined. This behavior in humans further validates the current animal model of deafferentation pain. PMID- 1408320 TI - Effects of acetaminophen and antipyrine on non-inflammatory pain and EEG activity. AB - Antinociceptive effects of the 2 (each 1000 mg, orally) non-steroidal anti inflammatory drugs (NSAIDs) acetaminophen (paracetamol) and antipyrine (phenazone) were investigated with a non-inflammatory experimental pain model in 32 healthy volunteers. Phasic pain was induced by intracutaneously applied brief electrical pulses (20 msec). Pain ratings, cerebral potentials and the EEG delta power were measured in response to the stimuli. Unspecific effects upon the vigilance system were evaluated by spontaneous EEG, auditory evoked potentials and reaction times. The investigation was performed as a placebo-controlled, double-blind crossover study. Blood samples were taken to monitor the plasma concentrations of the active agents. Ninety minutes after medication the 2 NSAIDs produced similar effects upon all pain-relevant target variables, although the mean plasma concentration of antipyrine (15 micrograms/ml) was approximately twice that of acetaminophen (7.5 microgram/ml). Both NSAIDs reduced pain ratings by 6%, late cerebral potentials by 19%, and stimulus-induced delta power of the EEG by 21%. The antipyrine effects emerged earlier, in agreement with its faster kinetics. Both NSAIDs could be differentiated by their effects upon spontaneous EEG activity. Whereas acetaminophen mainly enhanced the power in the theta range, antipyrine predominantly depressed the alpha frequencies. None of the drugs influenced auditory evoked potentials and reaction times. The central effects of acetaminophen and antipyrine are discussed with respect to antinociception and decrease in vigilance. PMID- 1408321 TI - Allodynia evoked by intrathecal administration of prostaglandin F2 alpha to conscious mice. AB - The intrathecal administration of prostaglandin F2 alpha to conscious mice resulted in spontaneous agitation and touch-evoked agitation (allodynia) in the animals. The maximum allodynia induced by prostaglandin F2 alpha was observed at 10-15 min after intrathecal injection, and the response did not disappear by 120 min. Prostaglandin F2 alpha produced allodynia over a wide range of dosage from 0.1 pg to 2.5 micrograms/mouse. Dose dependency of prostaglandin F2 alpha for allodynia showed a skewed bell-shaped pattern, and the maximal allodynic effect was observed at 1.0 microgram. This allodynia was dose-dependently relieved by alpha 1-adrenergic (methoxamine), alpha 2-adrenergic (clonidine), and A1 adenosine (RPIA) agonists. Clonidine was 1.5 orders of magnitude more potent than methoxamine in blocking prostaglandin F2 alpha-induced allodynia. The blockade by clonidine was dose-dependently reversed by the alpha 2-adrenergic antagonist yohimbine but not by the alpha 1-adrenergic antagonist prazosin. These results demonstrate that prostaglandin F2 alpha administered intrathecally induces allodynia in conscious mice and that the allodynia involves the alpha 2 adrenergic and A1-adenosine systems. Because this allodynia has a clear resemblance to the characteristics of chronic pain in patients with causalgia and reflex sympathetic dystrophy, prostaglandin F2 alpha may be involved in allodynia observed with these disorders. PMID- 1408322 TI - Pain threshold in diabetic rats: effects of good versus poor diabetic control. AB - Pain threshold was assessed via tail flick latency in streptozotocin diabetic rats following a 1-month period of either good or poor diabetic control. Additionally, tail flick latencies were determined under test conditions of euglycemia (60-120 mg/dl) and hyperglycemia (greater than 250 mg/dl) for both groups of diabetic rats. Conditions of hyperglycemia resulted in a significant decrease in tail flick latency in diabetic animals maintained in good as well as poor diabetic control. However, tail flick latencies for animals in the good but not in the poor diabetic control group increased when animals were euglycemic at the time of testing. Animals in the poor diabetic control group continued to have reduced tail flick latencies even after acute normalization of blood glucose levels. These results suggest that chronic states of hyperglycemia that attend prolonged periods of poor diabetic management may lead to persistent alterations in pain threshold. In contrast, the reduced pain threshold of rats maintained in good diabetic control was reversed by a normalization of blood glucose levels. These findings provide evidence for two patterns of hyperalgesia in diabetic rats: (1) a readily reversible form in well-maintained diabetic rats that is altered by reducing circulating blood glucose levels to control values and (2) a more persistent form found in poorly controlled diabetic rats that does not respond to acute normalization of blood glucose. PMID- 1408323 TI - Comments on Syrjala et al., PAIN, 48 (1992) 137-146. PMID- 1408324 TI - Comment on Banning, Sjogren and Henriksen, PAIN, 47 (1991) 129-134. PMID- 1408325 TI - Comments on Padawer and Levine, PAIN, 48 (1992) 132-135. PMID- 1408326 TI - Comments on Padawer and Levine, PAIN, 48 (1992) 132-135. PMID- 1408327 TI - Comments on Max et al., PAIN, 45 (1991) 3-9. PMID- 1408328 TI - Duplex scanning evaluation of internal carotid stenosis. Improved detection of early lesions. AB - New criteria for the interpretation of duplex scanning waveforms were compared with those devised by Blackshear and Strandness and revealed an improved grading of internal carotid stenosis in early lesions. The ratio of peak frequency minus first zero slope frequency divided by the peak frequency (a-b/a ratio) was found to be of no value in the discrimination between normal and any grade of carotid stenosis. The new criteria depend upon the to dental presence of spectral broadening on the upstroke of systole to differentiate between normal and abnormal, spectral broadening throughout the systolic phase above the end diastolic frequency to determine greater than 15% stenosis, peak frequency greater than 4kHz to indicate greater than 50% stenosis and the absence of a Doppler signal to indicate occlusion. Comparison with two plane selective carotid angiography revealed a Kappa statistic of 0.8 +/- 0.02 using the new criteria compared with 0.65 +/- 0.03 using the established criteria of Doppler waveform analysis. PMID- 1408329 TI - The LMI test in colon, breast and lung cancer long survivors. AB - Cell-mediated immunity towards tumour antigens (cytosols) of the same histotype and site was evaluated by means of the LMI test in long survivors after surgical resection of adenocarcinoma of the colon, infiltrating ductal carcinoma of the breast, and squamous-cell carcinoma of the lung. A positive migration index (MI less than 85.0) was observed in 17/65 (26.2%) colon survivors, 7/18 (38.9%) breast survivors, and 1/19 (5.3%) lung survivors. 24.5% of all long survivors displayed an immunological memory of the antigen to which they had been exposed. PMID- 1408330 TI - Prognostic value of Pugh's modification of Child-Turcotte classification in patients with cirrhosis of the liver. AB - The Child-Turcotte classification, as modified by Pugh et al., was recorded on diagnosis in 598 completely followed patients with cirrhosis of the liver. The variables that comprise the Pugh classification are ascites, encephalopathy, serum albumin, serum total bilirubin, and prothrombin time. The Pugh score categorized in three classes (class A = score 5 or 6, class B = score 7 to 11, class C = score 12 to 15) separates the series into three groups of approximately equal size with significant differences in median survivals (p less than 0.005) and in survival curves (p less than 0.0001). The characteristics of simplicity, availability, low cost and good discrimination power make the Pugh classification a very useful method to estimate prognosis in patients with cirrhosis of the liver. PMID- 1408331 TI - On extravisceral soft tissue sarcomas. Effectiveness of radiation treatment and problems of radiotherapy and radiosurgical treatment. AB - A series of 355 extravisceral soft tissue sarcomas is presented with reference to the effectiveness of radiation treatment for each histological type and the problems of radiotherapy and surgical treatment. Liposarcoma was the most radiosensitive soft tissue sarcoma. By utilizing all types of treatment and especially radiosurgery with postoperative radiotherapy, the percentage of disease-free patients after a minimum of 3 years from treatment varied from 27% to 52.9% for the different types of sarcoma. Nevertheless, in most cases the effectiveness of radiotherapy was unpredictable. It was found that doses varying from 52-60 Gy, with 2 Gy for each of 26-30 applications within 6-8 weeks, were sufficient for radical treatments. In relation to unpredictability of radiotherapy results, it was concluded that preoperative was more advisable than postoperative treatment owing to the possibility to prove the effectiveness of radiotherapy. Postoperative treatment is useless in nonradiosensitive cases and might negatively affect surgical modalities. PMID- 1408332 TI - Evaluation of skin laceration repair by tissue adhesive in the pediatric emergency room. AB - The effectiveness of skin laceration repair by tissue adhesive has been evaluated, by comparison also with thread suture and steristrip application, in 926 0-15-year-old patients referred to the Emergency Room of our Institute during 1988. Tissue adhesive has been carried out more frequently in younger children and in some wound localizations especially at the face. At follow-up good aesthetic and functional results were observed. The rare complications, being related to incorrect choice of site application, can be avoided by following appropriate directions for use. Considering the compliance of the patients and their family, this non invasive technique of repair seems to be particularly suitable in childhood. PMID- 1408333 TI - Importance of oesophageal manometry in the diagnosis of oesophageal motility disorders. Report of two cases. AB - Two cases of dysphagia, in which radiology led to an incorrect diagnosis, are described. In case I the X-ray barium swallow showed only minor oesophageal dilatation with no apparent delay in emptying or abnormality of the cardias, yet achalasia was diagnosed by oesophageal manometry. In case 2, although the barium swallow strongly suggested achalasia, manometry showed a less severe motility disorder characterized by lower oesophageal sphincter dysfunction and normal peristalsis. Correct diagnosis obtained with manometry was supported by the different clinical course of the two patients during a 2 year follow up. Oesophageal manometry should always be performed when radiology and/or the patient's history suggest the presence of a motility disorder of the oesophagus since a correct diagnosis is essential for appropriate treatment and follow-up. PMID- 1408334 TI - Heterogeneous derangement of cellular sodium metabolism in Bartter's syndrome. Description of two cases and review of the literature. AB - The basic tubular alteration present in Bartter's syndrome is still a subject of controversy. The possibility that a generalized defect in transmembrane ion transport underlies the disease has been extensively investigated. Previous evaluations of cellular sodium metabolism in Bartter's patients showed extremely variable findings. In the present study we have examined in red blood cells of two patients with Bartter's syndrome the intracellular Na+ and K+ concentrations, the activity of ouabain-sensitive Na+/K+ pump, furosemide sensitive Na+/K+ cotransport, Na+/Li+ countertransport, and the rate constant of Na+ and K+ passive permeability. We have compared these values with those of a control group. Ouabain-sensitive Na+/K+ pump activity was decreased in both patients, whereas Na+/Li+ countertransport was activated. One of the patients also exhibited markedly decreased intraerythrocyte K+ concentration and decreased furosemide-sensitive Na+/K+ cotransport. The other had increased Na+/K+ cotransport activity and Na+ passive permeability. Intracellular Na+ and passive permeability to K+ were normal in both subjects. Our results are partially consistent with previously reported observations, and indicate the existence of heterogeneous alterations of erythrocyte sodium transport systems in patients with Bartter's syndrome. Although some of these alterations could be secondary to the electrolyte metabolism derangements of this disease, others might be genetically transmitted and could cause the different renal tubular defects shown in Bartter's disease so far. PMID- 1408335 TI - Histoplasmosis in an HIV-negative Italian man with mycosis fungoides. AB - The authors deal with a case of Histoplasmosis in a 50 yr old Italian man without any history of risk exposure to HIV infection and suffering from mycosis fungoides. Although this infection is rare in Europe and particularly in Italy, this case suggests the possibility that soils capable of supporting the saprophytic fungus growth are present even out of the endemic areas. PMID- 1408336 TI - Tracheal bronchus associated with bronchiectasis. Case report. AB - The authors describe a case of ectopic tracheal bronchus (TB) in a 42 years old female. This TB presented bronchiectasis determining various episodes of inflammation in the pulmonary district depending on it. The result of those episodes was atelectasis and fibrotic alterations of the superior right lobe. The mean diagnostic procedure was bronchography. Surgical treatment was performed (superior right lobectomy) with a good result controlled in a 5 year follow-up. PMID- 1408337 TI - Recent developments in neurosurgical spinal cord monitoring. AB - In a review 8 years ago, the then current status of intraoperative spinal cord monitoring (SCM) was discussed. Concerning future developments, that article concluded that the major challenge lay in (a) the improvement of the reliability and clinical relevance of somatosensory evoked potential (SEP) monitoring, where the incidence of false-negative and false-positive results had to be reduced, and (b) the application of new techniques like motor evoked potential (MEP) monitoring, which might turn out to be a method complementary to the SEP approach. Since that time, there has been a considerable amount of newly published results from intraoperative SCM, although clinical articles on exclusively neurosurgical SCM are rare (Table I). A selective literature search for the present review (primarily for the time from 1988 to 1992) yielded more than 200 citations. Eighty-one studies entered into the final evaluation; among these were 3 conference proceedings, 6 book chapters, and 10 review articles. Further, 40 clinical articles, and 22 articles on experimental work were counted. In particular, experimental studies in animals have given support to clinical monitoring by exploring the usefulness of new stimulation and recording techniques. This reappraisal only considers recent work on SEP and MEP in neurosurgical SCM with some experimental studies relevant to clinical SCM. Spinal cord monitoring in orthopaedic surgery is not evaluated in this review for reasons detailed in the article. PMID- 1408338 TI - Mortality, morbidity, and psychosocial outcomes of persons spinal cord injured more than 20 years ago. AB - Mortality, morbidity, health, functional, and psychosocial outcomes were examined in 834 individuals with long term spinal cord injuries. All were treated at one of two British spinal injury centres: the National Spinal Injuries Centre at Stoke Mandeville Hospital or the Regional Spinal Injuries Centre in Southport; all were 20 or more years post injury. Using life table techniques, median survival time was determined for the overall sample (32 years), and for various subgroups based on level and completeness of injury and age at injury. With the number of renal deaths decreasing over time, the cause of death patterns in the study group as it aged began to approximate those of the general population. Morbidity patterns were found to be associated with age, years post injury, or a combination of these factors, depending upon the particular medical complication examined. A current medical examination of 282 of the survivors revealed significant declines in functional abilities associated with the aging process. Declines with age also were found in measures of handicap and life satisfaction, but three quarters of those interviewed reported generally good health and rated their current quality of life as either good or excellent. PMID- 1408340 TI - Traumatic injury to the spinal cord. Prevalence in Brazilian hospitals. AB - Traumatic spinal cord lesions have a worldwide high morbidity and mortality, and in many developed countries the problem has received special attention, based on epidemiological studies. In Brazil these studies have been restricted to institutional data. In 1988 a survey conducted by the Integrated System of Traumatology and Orthopaedics, covering 36 public hospitals from 7 Brazilian capitals, revealed a point prevalence of 8.6% (108 patients) with spinal cord injury, aged from 6-56 years; 81% were men. The most frequent causes were traffic accidents (42%), firearms (27%) and falling from heights (15%). The main complications were pressure ulcers (54%) and urinary infections (32%). PMID- 1408339 TI - An audit of five years' experience of pregnancy in spinal cord damaged women. A regional unit's experience and a review of the literature. AB - In a retrospective review of pregnancy and delivery in 8 spinal cord damaged women managed at Hexham General Hospital Spinal and Maternity Units between 1986 and 1991, antenatal complications included urinary tract infection, anaemia, constipation, suspected deep venous thrombosis and pressure sores. Five of the 8 patients had adductor spasms. Autonomic hyperreflexia occurred in 2 patients in the antenatal period, and in one patient in the postpartum period. Four patients were delivered by caesarean section, and 4 of the 8 patients had breech presentation of the foetus at delivery. The perinatal outcome was good. PMID- 1408341 TI - Traumatic spinal cord injuries in Turkey. AB - Spinal cord lesions have various aetiologies, and trauma is one of the leading causes. Patients with spinal cord injuries (SCI) often have motor, sensory and autonomic dysfunctions and require a multidisciplinary rehabilitation programme. In this study 1694 SCI patients were investigated, including the frequency, and the distribution by age, sex, profession, aetiology, clinical status and year of occurrence. Traumatic SCI is more frequent among males than females and among those between the ages of 15 and 39 years. Regarding the aetiology, traffic accident comprised 35.41% of the total cases, the second most common cause was falls with 29.51%, and the third was high velocity bullet wounds: 21.95%. PMID- 1408342 TI - A clinical exercise system for paraplegics using functional electrical stimulation. AB - A low cost clinical exercise system was developed for the spinal cord injured, based on a bicycle ergometer and electrical stimulation. A pilot project was conducted, using the system, to examine the effects of stimulation induced cycling in long term paraplegics. The project comprised 2 phases of exercise, a strengthening phase involving a 12 week programme of electrical stimulation to the quadriceps and hamstrings and a 12 week cycling phase. Physiological, morphological and biochemical parameters were measured for each subject, at the beginning of the programme and following each phase. Results showed that a programme of stimulation induced lower limb exercise increased the exercise tolerance of all patients, as determined by a progressive increase in exercise time, cycling rate and exercise load. The enhanced exercise tolerance was a result of increases in local muscle strength and endurance. Increases in thigh muscle area and joint range of motion were recorded and all incomplete subjects reported an improvement in functional capabilities and general wellbeing. PMID- 1408343 TI - Tracheostomy in spinal cord injured: frequency and follow up. AB - Among 600 traumatic spinal cord injured (SCI) patients admitted during a 20 year period, 67 had a tracheostomy performed (11.2%). Of these 67 patients 46 had a cervical SCI. A concomitant thoracic trauma had occurred significantly more often in the group with thoracic or lumbar SCI than in those with a cervical SCI. The period from injury to tracheostomy was 0-48 days (median 4.4 days), and from tracheostomy to decannulation 3-167 days (median 31 days). At follow up 20 (30%) had died, primarily because of respiratory problems. Of the remaining 47 patients, 43 (91%) responded to a follow up questionnaire 3.5-21.7 years (median 10.4 years) after the injury. In the follow up 53% reported never to have had any inconvenience or trouble related to the tracheostomy. The major inconvenience among the others had been of cosmetic origin (28%), and 3 had had a surgical revision for this reason. At the time of follow up 9 patients (21%) still had certain complaints, primarily described as difficulty in swallowing. Minitracheostomy might in the future reduce the number of these complications. PMID- 1408344 TI - Cystic cord lesions and neurological deterioration in spinal cord injury: operative considerations based on magnetic resonance imaging. AB - In a retrospective review of 94 consecutive patients with past spinal cord injury referred for magnetic resonance imaging (MRI) for the evaluation of new neurological symptoms, 59% were found to have cystic spinal cord lesions. Twelve of these patients underwent surgical cyst drainage, half having presented with increased myelopathy, and half with ascent of the neurological level. All of the operated cysts were greater than 2 cm in diameter (mean 15.8 cm), and 4 had areas of signal void indicating turbulent flow. All 12 patients had clinical improvement following surgery. The future prospective use of MRI in patients with longstanding spinal cord injury may prove valuable in the identification of patients with syrinx formation, at risk of developing neurological deterioration, who may benefit from early cyst drainage. At present, however, the decision to operate on these patients should be based primarily on clinical criteria. PMID- 1408345 TI - Electromyographic registration of diaphragmatic fatigue during sustained trunk flexion in cervical cord injured patients. AB - When performing forward trunk flexion, cervical cord injured (CCI) patients exhibit continuous and high EMG activity in the diaphragm and elevated abdominal pressures. This study addressed the question whether the trunk flexion manoeuvres cause such a high force development in the diaphragm that this muscle shows EMG signs of fatigue. Six patients with complete cervical cord lesions were tested sitting in their own wheelchairs. The tension-time indices obtained when patients were sitting in a relaxed position were moderately to markedly higher than in normal subjects. The force developed during trunk flexion averaged 30% of the maximal transdiaphragmatic pressure and was accompanied by clear EMG findings of diaphragmatic fatigue in all patients except one. The acute diaphragmatic load in certain CCI patients may well produce ischaemia and increase the risk of tissue impairment. Therefore, there appears to be a need for differing strategies in the short and in the long term treatment of CCI patients; longitudinal evaluation of main diaphragmatic function may be useful for an adequate amount of respiratory muscle training. PMID- 1408346 TI - Solitary spinal osteochondroma causing neural syndromes. AB - Three cases of solitary osteochondroma of the spine are reported. Two presented with cervical myelopathy and one with radiculopathy. Plain radiography or tomography is adequate for the diagnosis in the majority of cases; nevertheless, a CT scan or MRI is of immense help in planning surgical treatment. The radiological features of spinal exostoses are reviewed. PMID- 1408347 TI - Pathogenicity of Actinomyces israelii and Arachnia propionica: experimental infection in guinea pigs and phagocytosis and intracellular killing by human polymorphonuclear leukocytes in vitro. AB - Strains of Actinomyces israelii and Arachnia propionica, isolated from clinical cases of failed endodontic therapy, were examined for: (i) their ability to survive and establish themselves in the soft connective tissue that grew into subcutaneously implanted tissue cages in guinea pigs; (ii) cell-surface hydrophobicity; and (iii) phagocytosis and killing by human polymorphonuclear leukocytes (PMNs) under aerobic and anaerobic conditions. Bacteria were inoculated into the tissue cages in guinea pigs and the cage contents were retrieved after 1, 7, 14 and 21 d for culturing and light and electron microscopy. Both bacterial species showed substantial decline in the number of bacteria by day 7 after the inoculation. Thereafter, the A. israelii strain recovered and, by day 21, had started to increase in number. Light and electron microscopy revealed the formation of typical actinomycotic colonies. A. propionica, on the other hand, continued to decline in number during the entire period of experimental infection and did not form colonies. Both strains were hydrophobic, readily phagocytosed and were efficiently killed by human PMNs under aerobic and anaerobic conditions in vitro. These results suggest that the pathogenicity of A. israelii is due to its ability to establish characteristic cohesive colonies consisting of branching filamentous organisms that are enmeshed in an extracellular matrix. It seems that the organisms existing in such colonies can collectively evade destruction and elimination by host phagocytic cells, whereas in vitro suspensions of the bacteria are easily phagocytosed and efficiently killed by PMNs. With respect to A. propionica, further investigations are necessary to understand its pathogenicity. PMID- 1408348 TI - Chronic peroral immunization of conventional laboratory rats with mutans streptococci leads to stable acquired suppression of salivary antibodies. AB - Prior investigations have demonstrated that salivary antibody responses to mutans streptococci are dose-dependent and temporary. The purpose of this study was to evaluate the stability of antibody suppression established by mutans streptococci. Streptococcus mutans 6715-15 was provided in food to conventional rats for 18 weeks. Antigen was withdrawn for 10 weeks and then resumed for an additional 6 weeks. Saliva and serum from nonimmunized controls and from experimental rats were tested with a quantitative enzyme-linked immunosorbent assay for IgA and IgG antibodies to whole bacterial cells and to soluble antigen. Results show that salivary antibodies were stimulated by primary peroral immunization, that IgA was the dominant isotype and that IgA antibodies were primarily directed against soluble antigen. This study also shows that immunity is not maintained, even while challenge continues, and that once suppression is established, immunized animals do not recover their ability to respond, even if exposure is stopped for 10 weeks before re-exposure. PMID- 1408349 TI - Assessment of the cariogenic potential of Streptococcus mutans strains and its relationship to in vivo caries experience. AB - Strains of Streptococcus mutans isolated from the plaque of 6 subjects were studied using an in vitro model to determine whether differences in their cariogenic potential could be detected, and if so, whether the results correlated with the caries experience of the individuals. Each strain was incubated with a bovine enamel slab and 5% (w/v) sucrose for 24-h periods. The acidogenic potential was assessed by pH measurement and analysis of acid anion production. Microradiographic and microdensitometric assessment of the enamel, together with measurement of the change in calcium concentration of the reaction mixture were used to determine the demineralizing potential of each strain. Significant differences in cariogenic potential were found between some of the strains tested, and correlations were found between 3 of the test parameters and the decayed-missing-filled-surface score of the individuals. The results suggest that the caries experience of individuals may be related, to some extent, to the cariogenic potential of their S. mutans strains. PMID- 1408350 TI - Purification and properties of sorbitol-6-phosphate dehydrogenase from oral streptococci. AB - The activity of sorbitol-6-phosphate (S6P) dehydrogenase (S6PDH) and the sorbitol transport system were studied in strains of the oral streptococci Streptococcus gordonii, Streptococcus mitis, Streptococcus sanguis and Streptococcus mutans. Genetically transformed (to ferment sorbitol) strains and their DNA donors were included. S6PDH was purified by anion exchange chromatography and gel filtration. The purity of the enzyme was confirmed by polyacrylamide gel electrophoresis. The purified enzyme from all the strains exhibited Michaelis-Menton saturation kinetics. The Km values for nicotinamide-adenine dinucleotide (NAD) and S6P ranged between 0.03 and 0.21 mM and 0.07 and 0.20 mM respectively. The relative molecular weights of the native enzyme were 229,000 for one donor-transformant pair (S. sanguis and S. gordonii), 107,000 for the other pair (S. mitis and S. gordonii) and 129,000 for S. mutans. The molecular weights of the S6PDH subunits ranged from 26,000 to 28,000. The pH optima (greater than 8.5) and the amino acid composition (15 amino acids examined) were similar for the S6PDH from the different strains. However, the chromatographic and electrophoretic patterns as well as the Km values for NAD and S6P were the same only between the S6PDHs from the strains within each donor-transformant pair. Purified S6PDH from S. mutans also exhibited low mannitol-1-phosphate dehydrogenase activity. Sorbitol-grown decryptified cells of all the strains phosphorylated sorbitol in the presence of phosphoenolpyruvate but not in the presence of adenosine triphosphate (ATP). ATP mediated phosphorylation of glucose was observed with the same strains when grown on glucose. No evidence for a non-phosphotransferase transport system was found for sorbitol in any of the strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408351 TI - Mechanism of water-insoluble glucan synthesis in Streptococcus sobrinus. AB - Synthesis of water-insoluble glucan (IG) by 1,3-alpha-D-glucan synthase from Streptococcus sobrinus was examined using methylation analysis. The purified enzyme was incubated with sucrose and dextran T2000 (DT2000) for a given time and only IG was harvested by centrifugation. The remaining supernatant was incubated again, and IG was obtained. By repeating the above method using the residual supernatant, we obtained 5 varieties of IG precipitated in different periods. These IGs were methylated and examined using gas chromatograph mass spectrometry. The DT2000 water-insolubilized in the early reaction stage tended to have a highly ramified structure, with 1,3-alpha-D-glucan on a 1,6-alpha-D-glucan chain as the main chain. On the contrary, the DT2000 water-insolubilized in the late stage tended to have sparse side chains of 1,3-alpha-D-glucan which elongated with incubation. Specifically, the greater the number of side chains, the sooner the DT2000 was insolubilized. These results suggest that water-insolubilization of the water-soluble glucan not only depends on the increase of the ratio of 1,3 alpha-glucoside linkages to 1,6-alpha-glucoside linkages but also on the degree of branching of the 1,3,6-alpha-branched glucoside linkages. PMID- 1408352 TI - Processes involved in the regulation of urease levels in Streptococcus salivarius by pH. AB - Urease levels in Streptococcus salivarius are regulated by pH. There is either increased synthesis at low pH (5.5) or enhanced degradation at neutral pH, suggested by urease instability during stationary phase. To establish which mechanism predominates, protein synthesis was inhibited by chloramphenicol (CAP) in cultures grown at pH 5.8, 6.8 and 7.3. There was no significant urease degradation detectable in mid-exponential and early-stationary phase at any pH. Urease degradation occurred in both control and CAP cultures later in stationary phase, but with a faster rate of decline in the low pH culture. After CAP addition there was detectable assembly of urease from pools of post-translational subunits to give an approximately 20% increase in enzyme. Above pH 7, 0.1% cysteine inhibited urease synthesis but not growth, and evidence was obtained for O2 inhibition of growth and urease synthesis. Regulation of urease levels in S. salivarius by pH primarily involves an effect on urease synthesis. There may be cross-regulation between pH control, anaerobiosis-controlled enzyme regulatory circuits and thiols. PMID- 1408353 TI - Stimulatory effect of bicarbonate on the glycolysis of Actinomyces viscosus and its biochemical mechanism. AB - The effects of bicarbonate on acid production by 4 human strains of Actinomyces viscosus were estimated under anaerobic conditions. The rate of acid production was accelerated by bicarbonate 3-4 times as much as that without bicarbonate. The analyses of intracellular glycolytic intermediates, NAD and NADH revealed a decrease in NADH:NAD ratio and an increase in the level of 3-phosphoglycerate in the cells when bicarbonate was present. Furthermore, when bicarbonate was available, malate dehydrogenase and fumarate reductase in the succinate pathway were expected to function as NADH-oxidizing enzymes in addition to lactate dehydrogenase. These observations indicate the efficient regeneration of NAD in the presence of bicarbonate. Thus, the stimulation of A. viscosus glycolysis by bicarbonate was thought to stem from the activation of glyceraldehyde 3-phosphate dehydrogenase (G3PDH) by the decrease in the level of NADH, because NADH was a strong inhibitor of G3PDH in this microorganism. PMID- 1408354 TI - DNA probes for detection of cariogenic Streptococcus mutans. AB - Streptococcus mutans has been identified as the principal etiological agent in human dental caries. Therefore, the specificity and sensitivity of 3 potential gene probes derived from S. mutans GS5 have been examined as potential reagents for detecting the cariogenic bacteria. The gene probes derived from the cloned gtfB, gtfD and ftf genes were examined in Southern blots with a panel of representative oral bacteria. The gtfB and ftf genes were apparently specific for S. mutans under high-stringency hybridization conditions. However, the gtfD gene fragment did cross-hybridize with the DNA from other mutans streptococci. These results suggest that gtfB and ftf gene fragments may be used as specific probes for S. mutans. PMID- 1408355 TI - Immunochemical and structural characterization of the antigenic polysaccharide from Eubacterium saburreum T18. AB - An antigenic surface polysaccharide produced by Eubacterium saburreum strain T18, isolated from human dental plaque, was purified from formamide extract of whole cells. Methylation analysis, Smith degradation, optical rotation data and nuclear magnetic resonance spectra demonstrated that the purified antigen was a homopolysaccharide composed of D-glycero-D-galacto-heptose (Hep.) residues. The structure of the repeating unit in the polysaccharide was: -[----6)-[alpha Hep.furanosyl-(1----4)]-beta-Hep.pyranosyl- (1----6)-[alpha-Hep.furanosyl-(1--- 2), alpha-Hep.furanosyl-(1----4)]-beta- Hep.pyranosyl-(1-)4----6)-beta Hep.pyranosyl-(1----. No heptose residues were acetylated. Immunodiffusion reactions in agar gel suggested that the immunodeterminant of the antigenic polysaccharide was D-glycero-D-galacto-heptofuranosyl residues as branched nonreducing terminals. PMID- 1408356 TI - A comparison of three methods for estimating dental plaque removal from individual teeth. AB - The purpose of this study was to determine the efficiency of dental plaque removal, in vitro, by physical force. Of the 3 methods used, turbidity was the most sensitive for measuring microgram amounts of plaque. Air-dried weight and dental plaque imprint assays (DPIA) complemented turbidity measurements by providing a weight standard and a new method for visualizing plaque bacterial structure before the stained imprint was transformed into numerical data. The amount of dental plaque removed from a tooth by physical force can be measured and described as a percentage of the total removable plaque on that tooth. PMID- 1408357 TI - Suppressive effect of soluble factor(s) derived from Prevotella loescheii ATCC 15930 on proliferation of human lymphocytes. AB - Soluble sonic extracts of Prevotella loescheii caused a dose-dependent inhibition of human peripheral blood lymphocyte proliferation by mitogen and of the proliferation of a leukemic cell line, BALL-1, when assessed by DNA synthesis (3H thymidine incorporation). RNA (3H-uridine incorporation) and protein (3H-leucine incorporation) synthesis were similarly altered after exposure to the extract. There was no effect on cell viability as measured by either trypan blue exclusion or extracellular release of the cytoplasmic enzyme lactate dehydrogenase. Preliminary characterization indicates the suppressive factor(s) derived from P. loescheii to be a protein since it is heat-labile and trypsin-sensitive. The factor eluted in a peak on a high-pressure liquid chromatography gel filtration corresponding to a molecular weight of approximately 32,000. Since black pigmented anaerobic rods have been implicated in the pathogenesis of periodontal disease, the data suggest that P. loescheii contributes to the disease process by suppressing lymphocyte function. PMID- 1408358 TI - Laminin binding to Prevotella intermedia. AB - The interaction of laminin (Lm), a basement membrane protein abundant in the periodontium, with 66 strains of Prevotella intermedia isolated from diseased pockets, was tested in a 125I-labeled protein binding assay. The mean binding value was 28% of the total protein added. The binding significantly increased to 35% when the environmental pH decreased from 7 to 6. The Lm interaction was characterized in a highly binding (about 65%) strain, OMGS105. The binding was rapid and required about 1 min and 1-2 h for 50% and 100% equilibrium respectively. The 125I-Lm binding was maximum in the pH interval 3.0 to 6.5 and could not be displaced by unlabeled Lm or inhibited by other proteins and carbohydrates. The interaction was stable in the presence of NaCl or urea (concentrations up to 4 M) but was dissociated by > or = 1 M KSCN. The Lm-binding component was thermolabile and sensitive to proteolytic enzymes. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western blot analysis revealed a approximately 62 kDa Lm-binding protein, both in the whole cell extract and the outer membrane preparation. Weaker binding was also observed to other proteins. These data establish the ability of P. intermedia to interact with Lm via certain cell surface proteins, a property that might contribute to the colonization of this bacterium in the periodontal pocket. PMID- 1408359 TI - Strain identification of Actinobacillus actinomycetemcomitans using the polymerase chain reaction. AB - A molecular assay that distinguishes among strains of the periodontal pathogen Actinobacillus actinomycetemcomitans was developed by identifying DNA restriction site polymorphisms in the highly variable transcribed spacer region between the 16S and 23S ribosomal genes. The polymerase chain reaction (PCR) was used to amplify this region from genomic DNA using primers within conserved regions of the 16S and 23S genes. This amplified region was digested using a series of restriction enzymes and electrophoresed. Examination of restriction fragment length polymorphisms obtained by separate digestion with RsaI and NciI allowed the 7 strains examined to be divided into 4 genetic groups. This assay provides a more precise and reproducible method of strain identification than whole genomic methods and should be useful as a method for studying the epidemiology of A. actinomycetemcomitans strains in human subjects. The genetic variability detected supplies strong evidence that direct sequence analysis of the region could provide extremely precise and potentially definitive identification of strains. PMID- 1408360 TI - Actinobacillus actinomycetemcomitans, Capnocytophaga and Porphyromonas gingivalis in subgingival plaque of adolescents with Down's syndrome. AB - Levels of Actinobacillus actinomycetemcomitans, Capnocytophaga and Porphyromonas gingivalis were determined in subgingival plaque samples from 37 adolescents with Down's syndrome and 37 healthy controls matched with respect to age and sex. Gingival inflammation, supra- and subgingival calculus, periodontal pockets ( > 4 mm) and alveolar bone loss were registered. Alveolar bone loss was more frequent in Down's syndrome subjects (32%) than in the controls (3%). A. actinomycetemcomitans was detected in the subgingival plaque in 35% of the Down's syndrome adolescents and in 5% of the controls. On site level, A. actinomycetemcomitans and Capnocytophaga were more frequent in the subgingival plaque samples of Down's syndrome children than in those of controls. Comparing Down's syndrome subjects positive or negative for A. actinomycetemcomitans and Capnocytophaga, no significant differences were found in terms of gingival inflammation, periodontal pockets ( > 4 mm) or number of sites with alveolar bone loss. The results indicate an altered microbial composition of the subgingival plaque of Down's syndrome subjects compared with healthy controls, with higher frequency of A. actinomycetemcomitans. PMID- 1408361 TI - Enterococci in human periodontitis. AB - Enterococci are potential pathogens in many human body sites. This study determined the subgingival occurrence and the in vitro antimicrobial susceptibility of enterococci in 100 persons with early-onset periodontitis and 545 persons with advanced adult periodontitis. Subgingival microbial samples were collected with paper points, transported in VMGA III and plated onto anaerobic enriched brucella blood agar or selective Enterococcosel agar (BBL Microbiology Systems). Enterococcal speciation was performed using commercial micromethod kit systems. In vitro sensitivity was determined using a commercial kit system and an agar dilution assay. Subgingival enterococci occurred in 1% of early-onset periodontitis patients and in approximately 5% of adult periodontitis patients. Enterococcus faecalis was the only enterococcal species recovered, and all but one isolate belonged to the same biotype. In vitro antimicrobial sensitivity testing revealed subgingival enterococci resistant to therapeutic levels of penicillin G, tetracycline, clindamycin and metronidazole, but relatively sensitive to ciprofloxacin and amoxicillin/potassium clavulanate (Augmentin). Enterococci may populate periodontal pockets as superinfecting organisms and, in heavily infected patients, may contribute to periodontal breakdown. PMID- 1408362 TI - Experimentally induced infection by oral anaerobic microorganisms in a mouse model. AB - A mouse model was developed to study the abscessogenic potential of pure and mixed cultures of oral anaerobes associated with infections of endodontic origin. Maximum subcutaneous lesions were seen on their backs between 3 and 14 d after inoculation. Strains of Fusobacterium nucleatum, Peptostreptococcus anaerobius, and Veillonella parvula were pathogenic in pure culture. A mixed culture of F. nucleatum with either Porphyromonas gingivalis or Prevotella intermedia was significantly more pathogenic than F. nucleatum in pure culture. Histopathological examination of tissue sections from control mice injected with India ink in the medium demonstrated a pathway of particulate migration from the backs of the mice to their abdomen. PMID- 1408363 TI - [The effect of the vole subspecies of the plague microbe on the viability of Callopsylla caspia fleas]. AB - When infected with cultures of plague microbe reared at 28 C the experimental fleas showed no reliable differences in the mortality as compared to control ones. By contrast, the infection with agent cultures reared at 37 C as well as the infection on agonizing white mice caused a statistically reliable increase in the mortality in insects of both sexes. In the groups of fleas infected on white mice the most intensive mortality was observed during the first 24 hours after the infectious feeding that, apparently, is connected with the effect of toxins present in the blood of agonizing animals. PMID- 1408364 TI - [A finding of Blastocystis galli (Rhizopoda, Lobosea) in domestic turkeys]. AB - Blastocysts tentatively assigned to the species Blastocystis galli were found in the turkey Meleagris gallopavo from Tajikistan and Uzbekistan. Length and width of blastocysts from turkeys vary in a wider range (2.5--55.1 x 2.5--51.3 mkm) than length and width of blastocysts from hens. The shape of blastocysts varies from round and oval to ellipsoid and amoeboid. PMID- 1408365 TI - [The parasite-host specificity of the itch mite Sarcoptes scabiei (Acariformes: Sarcoptidae) in man and animals (a review of the literature)]. AB - The primary parasitic relations between the itch mite Sarcoptes scabiei (L.) and man are confirmed indirectly by the presence in the family Sarcoptidae of close genera, members of which parasitize primates. Judging from the composition of domestic and wild animals-hosts, the source of their infection with S. scabiei was man that gave rise to numerous forms of mites specific to individual species of hosts or their related groups belonging to different taxonomic ranks. Three types of host relations and, accordingly, forms of sarcoptosis are suggested at the infection from an alien host: pseudosarcoptosis, temporary self-curable and typical lingering sarcoptosis. The ways of reinfection, invasiveness of stages of the mite and clinical picture for each form of the disease are analyzed. PMID- 1408366 TI - [The characteristics of the ixodid tick-vertebrate animal parasitic system]. AB - The parasitic system ixodid tick (parasite)--vertebrate animal (host) is relatively stable in space and time. Equilibrium state in the system is maintained at the low levels of the hosts' infection and moderate intensity of their immunity. Parasite sensitizes the host's organism at the stage of feeding on antigens of its saliva and the host develops different degrees of resistance preventing the subsequent individuals of ticks from normal feeding. Antitick immunity is species specific. Its intensity is defined by the species belonging of the parasite and host, intensity and intervals between infections, availability of "anti-immune mechanisms" in tick and by many other factors, which are realized at the feeding stage. Regulation of the number of ticks, depending on their abundance in the host's population, is attained due to the oversparse, close to negative binomial distribution on hosts. This mechanism functions on the principle of feedback, so that at the excessive number of the parasite some individuals in the host's population, which are especially subjected to infection, do not cope with parasitic burden and die. However, ticks, which failed to finish their feeding and represent a disproportionately great part of the whole parasite's population, die together with them and the parasitic system quickly restores its stability. In anthropocoenoses and ecosystems at different stages of anthropogenic transformation mutual regulation mechanisms of the parasite and host number break down. As a consequence, extremely high rises in the number of ticks and epizootics of agricultural animals associated with them can occur. PMID- 1408367 TI - [The penetration of Sporozoa into host cells]. AB - The analysis of morphological and functional peculiarities of sporo- and merozoites as disseminative stages of the sporozoan life-cycle is given. Penetration of parasites into the host's cells is a complex multistepped process very similar to the induced but not completed phagocytosis. As a result of that process the formation of the integrated cell system, which consists of the host's cell and the unicellular parasite takes place. PMID- 1408368 TI - [The characteristics of the helminth community in the Turkmen kulan (Equus hemionus)]. AB - The helminth fauna of 24 kulans from Askaniya-Nova and Badkhyz was studied. 42 species of helminths were found, 34 of which belong to strongylids. The helminth species composition of kulan is similar to that of other species of horses. This is a result of an intensive parasite exchange in the historical past when numerous populations of different Equidae species made long seasonal migrations over steppe inter-river lands of Asia and grazed for some time on common pastures. PMID- 1408369 TI - [Microsporidians in bloodsucking Aedes (O.) cataphylla mosquitoes in Ukraine]. AB - The paper reports the results of studies on Microsporidia from the bloodsucking mosquito Aedes cataphylla for the period from 1974 undertaken in the Kiev and Chernigov Provinces of the Ukraine. A new species, Amblyospora cataphyllus sp. n., is described from larvae of the mosquito. Living spores oval or elongate oval, 6.3--7.5 x 4.5--5.0 (most commonly 6.8 x 4.8) microns, fixed spores oval, 5.6--6.9 x 3.8--4.8 microns. Mucocalyx becomes distinct around spores in 10 to 15 days after the preparation is made. Spontaneously ejected polar tube 125 microns long. Exospore smooth or undulate, 170 to 310 nm thick, endospore 60 to 160 nm. Polaroplast elongated and curved, its 1/3 is composed of closely situated plates and 2/3 of more widely arranged ones. Polar tube anisophyllous, forms 18 to 20 spires in a spore, of which 3 to 5 spires form basal area and 14 to 16 form distal area (of them 1-2 most thick spires form intermediate area). Nucleus large, in a shape of half-ring. In living spores posterior vacuole crescentic, in fixed ones it is strongly deformed together with hind pole of spores. Sporogony of Microsporidia takes place in larvae of mosquitoes of both sexes. Infection extensiveness of IV stage larvae is 10%. PMID- 1408370 TI - Klippel-Feil syndrome. AB - Nurses working with orthopaedic clients and pediatric populations may be the first to recognize the classic triad of Klippel-Feil syndrome: short neck, limitation of neck motion, and low occipital hairline. Klippel-Feil syndrome is a congenital malformation of the cervical vertebrae, with limited treatment options. Client/family education is vital to monitor and maintain function and to prevent neurologic deficits resulting from the fusions, accidents, or trauma. PMID- 1408371 TI - Olecranon fracture. PMID- 1408372 TI - Total elbow replacement. AB - Elbow joint replacement is performed primarily in patients with severe elbow pain and elbow joint destruction caused by rheumatoid arthritis. The capitellocondylar implant is the prototype of the nonconstrained elbow resurfacing implant. Successful total elbow joint replacement can result in pain relief and improve rotation and flexion of the arm. Outpatient and inpatient nursing intervention in coordination with occupational therapy promotes optimum function. PMID- 1408373 TI - Developmental dysplasia of the hip. AB - Developmental dysplasia of the hip (DDH), formerly known as congenital dislocation of the hip (CDH), is a term used to describe a variety of abnormalities of the hip in development. The treatment options are diverse depending on etiology, degree of dislocation, and age of the child when diagnosis is made. This article provides the reader with a knowledge base to assist with early diagnosis, treatment, and nursing care of the client with dislocations and subluxations of the hip. Presented are the definitions, diagnostic techniques, treatments, and nursing diagnoses and interventions for the client with DDH and for the child's family. PMID- 1408374 TI - After Cruzan: the "values base" to advance directives. AB - Technologic advances produce ethical quandaries for health care professionals and the public. Often difficult decisions must be made about treatment. In light of the 1990 U.S. Supreme Court's ruling in the case of Nancy Cruzan, health care decisions surrounding life-sustaining treatment may be affected. National attention is refocused on advance directives (the living will and durable power of attorney for health care decisions). This article considers the possible need for additional "clear and convincing" evidence of the patient's wishes regarding these directives. Included is a Value History Form that provides an avenue of expression for patient values and beliefs. PMID- 1408375 TI - An election year debate: reforming the U.S. health care system. PMID- 1408376 TI - Postoperative orthopedic blood salvage and reinfusion. PMID- 1408377 TI - Angle Class I, skeletal Class II, with maxillary-mandibular crowding and bilabial protrusion. PMID- 1408378 TI - Working together means winning together. PMID- 1408379 TI - [Parvovirus B19 infection]. PMID- 1408380 TI - [Why are some trisomy 21 pregnancies carried to term?]. PMID- 1408381 TI - Expression of the T-cell receptor in HIV infection. AB - Expression of the T-cell receptor (TCR) was investigated on peripheral lymphocytes in 270 samples from HIV+ patients at different stages of infection. TCR is composed either of an alpha and a beta chain, or, in a smaller subset of T cells, of a gamma and a delta chain, closely associated with CD3. The numbers and percentages of positive cells were established using monoclonals to the alpha and delta chains of TCR. The values of alpha-TCR positive cells were constantly lower than those observed for CD3, with a mean of 53% (+/- 19%) versus 66% (+/- 17) respectively for asymptomatic patients or patients with persistent generalized lymphadenopathy, and of 36% (+/- 19) versus 46% (+/- 21) for patients with AIDS disease. There was no compensatory increase in the number of cells expressing delta-TCR. These data demonstrate a new alteration of the immune system in HIV infection, which appears to occur early in this disease. PMID- 1408382 TI - [Value of serum immunoglobulin assays in early myocardial infarction]. AB - Serum immunoglobulin (Ig) levels were assayed in 672 patients admitted for acute myocardial infarction with onset within 24 hours of hospitalization. Supranormal Ig levels (A > or = 300, G > or = 1,200) or subnormal Ig levels (M < 40 mg/100 ml) were seen in patients with one or several risk factors (diabetes mellitus, alcohol abuse) or a history of previous myocardial infarction. Patients with one or more Ig anomalies were more likely to exhibit unfavorable outcomes, including early death, suggesting that increased viscosity due to aggregation of Ig molecules may occur. PMID- 1408383 TI - [Value of quinolones in the treatment of lower respiratory tract infections caused by intracellular organisms, excluding mycobacteria]. AB - In vitro studies of quinolones against intracellular pathogens responsible for lower respiratory tract infections have shown that growth inhibition varies with the strain and with the drug. Following administration of quinolones, drug levels in the lower respiratory tract are similar to or greater than serum levels. Quinolones penetrate readily into cells. The effectiveness of quinolones in lower respiratory tract infections has been demonstrated in both in vitro intracellular infection models and in vivo animal models. These data show that quinolones are a valid therapeutic alternative for lower respiratory tract infections due to intracellular organisms. PMID- 1408384 TI - [Fibronectins]. AB - Fibronectins are complex glycoprotein macromolecules whose molecular weight is 440 kilodaltons. These proteins, found throughout the body, are soluble in biological fluids and insoluble in connective tissue. They contribute to tissue morphogenesis through multiple interactions with cells and extracellular matrix components. Fibronectins play a key role in cell attachment and remodeling during embryonic development, in cell migration and anchorage during wound healing, and in immune responses. This review discusses the structure of fibronectins, their integrin cell receptors, their biologic properties and their implications for diseases. PMID- 1408385 TI - [Relationship between left and right ventricular function in experimental acute focal ischemia]. AB - Experiments were conducted on rats to record the parameters characterizing the real and maximally accessible function of the left and right ventricles in acute focal ischemia of the myocardium of these parts 5, 20, 40, and 60 minutes after ligation of the corresponding coronary artery. It was established that disorders of synchronism in heart activity are greater in injury to the right than in those to the left ventricle. PMID- 1408386 TI - [Effect of a drug isolated from the heart on the bioenergetics of cardiomyocytes in hypoxia and ischemia]. AB - It has been established that cordialin inhibits selectively succinic acid oxidation and intensifies the exudation of a NADH2 substrate which is energetically more advantageous, and in this way has a favorable effect on energy metabolism, evidence of which is increase of the ATP content in the myocardium. Cordialin correction of the biologic energy of cardiomyocytes in hypoxia and ischemia prevents the accumulation of lipid drops in the cells of the peri infarction zone, which reflects the high intensity of the processes of fatty acids beta-oxidation. As a result of this glycolysis activation is unnecessary (which is confirmed by high glycogen content, both of a qualitative and quantitative character, in the myocardium and low concentrations of glucose and lactate in the blood) and, consequently, the sequelae of acidosis are prevented. PMID- 1408387 TI - [Role of the opioid system in prevention of ischemic disorders of cardiac rhythm during adaptation to cold and physical exertion in rats]. AB - It was found that adaptation of rats to cold and physical exercise prevented ventricular fibrillation caused by occlusion of the left anterior coronary artery. Adaptation to cold or only to physical exercise did not prevent ventricular arrhythmias. A significant increase of the beta-endorphin content in the hypophysis and hypothalamus was demonstrated in all adapted rats. An increased content of meth-enkephalin (ME) in the myocardium was found only in rats adapted to cold and physical exercise. It is suggested that increase of the myocardial ME content is of essential significance in the antiarrhythmic action of adaptation. PMID- 1408389 TI - [Mechanisms of the protective action of neoton in immune heart diseases]. AB - An attempt was made to reveal some membrane mechanisms of the protective effect of phosphocreatine (Neoton produced by the Schiappare firm, injected intravenously in a dose of 500 mg/kg) predominantly on the endothelium of the coronary vessels and the cardiomyocytes. Local immune damage to the left ventricular myocardium was produced by intracoronary injection of anticardiac antibodies. Morphological and biochemical studies showed damage to the membrane of endotheliocytes and cardiomyocytes: reduced activity of Na-Cametabolism and Na , K-ATPase. The obtained data bore evidence of the protective effect of phosphocreatine in immune damage to the heart, which was realized on the level of the endotheliocyte and cardiomyocyte membranes. PMID- 1408388 TI - [Correction of tetramethylthiuram disulfide-induced damage to the myocardium by cardiac peptides]. AB - Standardized complex of low-molecular peptides from the heart, cordialin, stimulates functional activity of cardiomyocytes and mobilizes their protective mechanisms against the effect of the industrial and agricultural poison tetramethylthiuram disulfide (TMTD). The cardioprotective effect of cordialin is most marked in the restoration period when it was administered after TMTD damage to the cardiomyocytes. PMID- 1408390 TI - [Changes in function of sarcoplasmic reticulum and myocardial phospholipid content in immune heart damage]. AB - The effect of acute cytotoxic reaction in the heart on Ca transport activity in the sarcoplasmic reticulum and the phospholipid content of the myocardium was studied. A single intracoronary injection of anticardiac serum reduced Ca, Mg ATPase activity and the Ca energy-dependent transport but caused no changes in membrane permeability to Ca. As the result of immune damage the content of phospholipids--cardiolipin and phosphatidylethanolamine--in the myocardium reduced. PMID- 1408391 TI - [Antistress and cardioprotective properties of the synthetic analog of endogenous opioids dalargin in experimental burn trauma in rats]. AB - The author studied the effect of Dalargin on the dynamics of experimental burn trauma in Wistar rats, which was evaluated according to values of lethality, the level of stress ulcero-erosive affection of the gastric mucosa, and the degree of functional activity of an isolated perfused heart. The antistress effect of Dalargin, consisting in limitation of ulcer formation in the gastric mucosa, was determined by dose-temporal characteristics which made it possible to develop the optimal schemes of Dalargin administration in the treatment of a burn trauma. This was manifested by reduced lethality among the experimental rats compared to that among the controls and marked limitation of stress ulcer formation and by significantly diminished cardiodepressive effect of burn toxemia. Besides, the protective effect of Dalargin was connected with the direct formation of resistance to hypoxia of the myocardium of rats with burns. PMID- 1408392 TI - [Dose-dependent effect of diltiazem on some lipid metabolic parameters in hemorrhagic shock in cats]. AB - The possibility of modulating the phospholipid composition in the plasma membranes of hepatocytes and adipocytes by the calcium channel blocker diltiazem was studied on a model of hemorrhagic shock. Diltiazem injection facilitated normalization of phosphatidylinositol metabolism in the hepatocyte plasma membranes. Injection of a high dose of diltiazem was attended by a rise of the phosphatidylethanolamine level. Only low doses of diltiazem caused a normalizing effect on the phospholipid composition of adipocyte plasma membranes. A low dose of diltiazem caused a reduction in the content of very low density lipoproteins in venous blood, while a high dose reduced the content of low density lipoproteins. PMID- 1408393 TI - [Antioxidant liver enzymes in chronic liver disease]. AB - Biopsy of the liver of 73 patients with chronic affection of the hepatobiliary system was conducted to study the enzymatic system of inactivation of the active forms of hepatic oxygen according to the stage of the chronic process. Reduced activity of superoxide dismutase and catalase and disruption of their relationship in chronic active hepatitis were revealed. Significantly diminished rate of inactivation of superoxide radicals was encountered in fibrosis and primary biliary cirrhosis. The informative importance of the catalase/NADP H peroxidase index in appraising chronic affection of the hepatic tissue is shown. It is concluded that the interrelation of the antioxidative enzymes as a system of antioxidant protection of hepatocytes is impaired in chronic diseases of the liver. PMID- 1408394 TI - [Role of the sympathetic nervous system in the formation of indomethacin-induced hemorrhage and ulceration of the stomach in albino rats]. AB - The authors studied changes of electrical activity of the gastroduodenal smooth muscles, sympathetic efferent impulses in the postganglionic branches of the celiac plexus and macro-morphology of the gastric mucosa during the development of indomethacin gastropathies. By the end of the 3rd hour and later after the injection of the drug (15, 30 mg/kg) progressive inhibition of impulses and basal rhythm of gastric smooth muscles was encountered in intensified electrical activity of the duodenal smooth muscles, as well as destructions in the gastric mucosa even to the development of ulcers (6-24 hours). It is concluded that the development of indomethacin hemorrhages and ulcerations along with other factors is caused by excitation of the sympathetic nervous system attended by phasic changes of the sympathetic efferent impulses and electrical activity of the gastroduodenal zone. PMID- 1408395 TI - [Effect of stress on translocation on the glucocorticoid receptor complex into the nuclei of rat hepatocytes]. AB - The effect of 24-hour immobilization stress on the translocation of glucocorticoid-receptor complex into the nuclei of hepatocytes was studied in experiments on male Wistar rats weighing 150-180 g. The level of translocation of the steroid-receptor complexes was appraised by incubation (0 degree C, 1 hour) of hepatocyte nuclei (6 x 10(-6)) with a glucocorticoid-receptor complex which was obtained by preliminary saturation of diluted hepatic cytosol with triamcinolone 3H-acetonide (80 nM) for 3 hours with adsorption of unbound labeled steroid. Translocation of the glucocorticoid-receptor complex of hepatic cytosol of rats subjected to stress occurred in a significantly less number into the hepatocyte nuclei of intact rats than into those of rats which had suffered stress. In contrast, translocation of the glucocorticoid-receptor complex of hepatic cytosol of intact rats into the nuclei of hepatocytes of stressed rats was significantly higher than translocation into hepatocyte nuclei of intact rats. It is concluded that the level of inhibition and activation of translocation in the cytoplasm of hepatic cells increases in stress. PMID- 1408397 TI - [Ultrastructure of erythrocytes with diminished flow properties and their role in the development of microcirculatory disorders under extreme conditions]. AB - The deformability (D) of erythrocytes and their ultrastructure in the microcirculatory channel of vital tissues of the organism were studied in experiments on rabbits in two types of extreme conditions: staphylococci toxicosis and the postischemic syndrome. Erythrocyte deformability in each of these extreme conditions occurred in the late phase of the process and was manifested by destruction of the ultrastructural organization of the membrane matrix and the cytoplasm of cells in the microvessels. Destruction of the erythrocyte membranes was linked with their disintegration into micro- and macro fragments (in staphylococci toxicosis) and separation of membrane areas in the form of microvesicles (in the postischemic syndrome). Damage to the erythrocyte membrane and cytoplasm may be considered to be one of the typical manifestations of the organism's response to extreme effects accompanying the phenomena of disseminated intravascular clotting. PMID- 1408396 TI - [Free radical peroxidation mechanisms of the pathogenesis of ischemia and myocardial infarction and their pharmacologic regulation]. PMID- 1408398 TI - [Status of the erythron during growth of induced tumors]. AB - The authors conducted complex (with the use of radionuclide, cytospectrophotometric, electron microscopic, interfermometric, and other methods) examination of the morpho-functional condition of the central and peripheral erythron links in rats during the development of tumors induced by 20 methyl-cholanthrene administration. It was found that increased hemolysis of mature circulating red cells plays the principle role in the pathogenesis of anemia developing in the experimental animals. The early periods of the hemolysis may be detected in the latent period of cancerogenesis. PMID- 1408399 TI - [Mechanisms of post-traumatic anemia]. AB - Diminution of hemolytic anemia in animals with bilateral nephrectomy was demonstrated in experiments on rats and dogs with trauma (24-hour crush syndrome). The mechanism of early posttraumatic erythrodieresis is linked with the effect of humoral hemolytic factors and injury to the poorly-stable red cell population during passage through the renal vessels of the animals 24 hours after the traumatic damage. PMID- 1408400 TI - [Rate of progress of chronic renal insufficiency during low-protein diet]. AB - The rate of progress of chronic renal insufficiency (CRI) under conditions of a diet with a moderate protein content and during a free diet was studied in 40 children with tubulointerstitial renal diseases and glomerulonephritis by determining the dependence of reciprocal serum creatinine on the time. A low protein diet had a positive effect on the rate of CRI progress in children with tubulointerstitial diseases of the kidneys. The prognostic error--the difference between the foretold and the true period of time to the "death of the kidney" was 12% on the average. PMID- 1408401 TI - [Effect of sodium fluoride on bone tissue regeneration in hypodynamia]. AB - It was demonstrated in rat experiments that a nonsupported position of the extremity attained by exarticulation of the leg in 10 to 40 days leads to a sharp inhibition of posttraumatic regeneration of bone tissue. Daily injection of 0.4 mg/100 g sodium fluoride, which was used in the clinic for the prevention and treatment of osteoporosis, inhibited still more the regenerative processes both under conditions of hypodynamia and also when the supporting function of the extremity was maintained. PMID- 1408402 TI - [A restraining device for simulating radiation sickness]. PMID- 1408403 TI - Highs and lows in breast-feeding rates. PMID- 1408404 TI - Breast or bottle: practical aspects of infant nutrition in the first 6 months. PMID- 1408405 TI - A glimpse into the future of infant nutrition. PMID- 1408406 TI - Three important minerals--calcium, iron, and fluoride. PMID- 1408407 TI - Myths about childhood obesity. AB - Childhood obesity is a multifactorial and complex disease. Myths such as those that we have described may distract our patients from the underlying behaviors that contribute to the disease or may deflect the blame perceived by obese patients and their parents. Myths that suggest that the obese are inactive, eat differently, or eat more junk food suggest that obese individuals are socially deviant and justifies the intense discrimination directed against them. The myth that obesity represents an untreatable disease helps free health-care professionals from the responsibility to understand and care for obese children. Dispelling the myths about childhood obesity represents a critical step in prevention and treatment. PMID- 1408408 TI - Allergy, intolerance, and other adverse reactions to foods. AB - Adverse reactions (sensitivity) to foods are categorized as either allergic (immunologic) or intolerance (nonimmunologic). Some medical conditions caused by intolerance reactions have immunologic features, but these have not adequately explained the basis of these conditions. Idiosyncratic, toxic, and anaphylactoid reactions may resemble allergic reactions clinically even though they are not based on specific immunologic events. Complaints about adverse reactions to foods are common but most cannot be reproduced by challenge studies. This fact reflects the transient nature of many of these reactions and should prompt the pediatrician to be objective when diagnosing chronic or persisting conditions. Without objectivity, dietary avoidance measures potentially can have profound nutritional and psychosocial consequences. Negative skin-prick tests with foods have a high negative predictive value to rule out IgE-mediated mechanisms being operative. Skin-prick testing with cow's milk and hydrolysate formulas is useful in distinguishing mild "topical reactors" from the more severe "systemic reactors" and in selecting "hypoallergenic" formulas for their management. However, the DBPCFC is the "gold standard" that helps distinguish between reality and strongly held erroneous beliefs. This diagnostic test has established cow's milk, egg, peanut, and soybean as the foods most commonly responsible for allergic and intolerance reactions in children. The principles of management of these food-related conditions are similar. However, each food presents unique management issues to the pediatrician. PMID- 1408409 TI - Incorporating nutrition into pediatric practice: physicians and dietitians working together to improve children's health. AB - Clinicians are needed to include nutrition in the routine care of infants and children in office practice. Physicians play an important role in assessing nutritional status, diagnosing nutritional problems, providing a rationale for treatment, prescribing, performing brief counseling, referring to other resources if needed, and following up on the progress of their patients. Registered dietitians are the consultants of choice to assist pediatricians in the care of patients with nutrition-related disorders and are skilled in providing pediatric health promotion and disease prevention information. Consultant dietitians in the community can be found through contacting the local department of health or local hospital outpatient department. The American Dietetic Association also maintains a list of consulting dietitians throughout the United States. Funding mechanisms for engaging dietetic services vary from contracting with dietitians in private practice, local health departments, or hospital outpatient clinics, to employing dietitians on-site to provide counseling services in the office. Availability for third party payment for nutrition services varies with insurance carriers, individual policies, and region of the country. Incorporating nutrition into pediatric practice is important. Together, physicians and dietitians can work together to improve children's health. PMID- 1408411 TI - Injury control: issues and methods for the 1990s. PMID- 1408410 TI - Causes of death among the young. PMID- 1408412 TI - Drowning in early childhood. PMID- 1408413 TI - Stop carelessness? No, reduce burn risk. PMID- 1408414 TI - Pediatric firearm injuries: time to target a growing population. PMID- 1408415 TI - Rehabilitation following childhood injury. PMID- 1408416 TI - Risk and prevention of youth suicide. AB - The rate of fatal suicide attempts among males rose dramatically between 1950 and 1980 and has continued to rise significantly during the 1980s among 15- to 19 year-old youth. Nonfatal suicide attempts, although far more frequent among females, appear to share similar risk factors with completed suicide. The most important preconditional risk factors for both fatal and nonfatal suicide attempts are a history of a previous attempt, major affective and conduct disorders, chronic substance abuse, and a history of personal losses, including experience of suicide attempts by peers and family members. Risk factors for the acute precipitation of an attempt include the acute disruption of an interpersonal relationship, alcohol intoxication, and access to firearms. Preventive efforts can be enhanced by pediatricians both in the office and the community. Clinical case finding of individuals thought to be at high risk will continue to identify some potential victims. Families with household firearms should be counseled regarding the risk of firearm injury and death, particularly in a home with an individual with other risk factors. Community campaigns to improve the mental health of youth and to reduce firearm ownership may hold future promise for the reduction of the unacceptable morbidity and mortality associated with adolescent suicide attempts. PMID- 1408417 TI - The ABCs of pediatric LFTs. AB - Liver function tests (LFTs) are an essential assessment parameter when evaluating a child's liver function. This article reviews the interpretation of LFTs and summarizes physioanatomic considerations. PMID- 1408418 TI - Living with chronic pediatric liver disease: the parents' experience. AB - Parents' perceptions of living with a child with serious, chronic liver disease were explored using a qualitative methodology. Six central themes emerged from interview transcriptions: beginning, sense of inadequacy and guilt, pain and stress, lack of control, taking control, developing a personal philosophy, and uncertainty and fear of the future. PMID- 1408419 TI - Impact of the child's liver transplant on the family: maternal perspective. AB - This study's purpose was to examine the impact of the child's liver transplant on posthospitalization family adaptation. The family adaptation model provided the framework. Social support was the only variable significantly correlated with family adaptation. PMID- 1408420 TI - Pediatric discharge planning. AB - This article will review the discharge planning process and discuss five significant distinctions specific to children that must be considered in order to provide quality care. These distinctions are: recognizing differences in pediatric diagnoses, delivering care to children of varying developmental levels, selecting appropriate resources, accessing educational interventions, and financing health care. PMID- 1408421 TI - Leech therapy: new procedures for an old treatment. AB - Experiences of pediatric ICU nurses as they cared for a child requiring leech therapy are described in this article along with the clinical conditions and therapy of the case. The nurses' ambivalence about participating in what seemed to be an archaic therapy and how they had to put such feelings aside to support the family are explained. PMID- 1408422 TI - Pediatric management problems (chondromalacia of the patella). PMID- 1408423 TI - Acyclovir in the treatment of chickenpox. AB - Although chickenpox is a highly contagious disease affecting 90% of susceptible persons exposed, its morbidity and mortality in healthy patients is minimal. Treatment of chickenpox with oral acyclovir appears to decrease the number of pox lesions and shorten the duration of new lesion formation. Most importantly, children treated with acyclovir begin to feel better soon and had fewer systemic signs and symptoms of chickenpox (fever, fatigue, loss of appetite). However, the greatest mortality from chickenpox is seen in the immunocompromised patient, or in elderly patients with zoster (shingles) due to reactivation of latent varicella infection. Therefore, prevention of varicella is necessary to decrease mortality from the varicella-zoster virus. It is hopeful that the varicella vaccine will be licensed in the U.S. for routine immunization of healthy children within the next year. While its general use will not eliminate either chickenpox or zoster, there will be a considerable decrease in the morbidity and mortality caused by this agent as a result of routine immunization. PMID- 1408424 TI - Selecting a home care agency. AB - Selecting a home care agency must be a collaborative effort on the part of families and the discharging facility. Guidelines for selecting home care providers eases the transition from the acute care facility to home. PMID- 1408425 TI - Far above rubies: the founders of Every Child By Two. AB - The Every Child By Two Campaign was formed by Rosalynn Carter and Betty Bumpers, spouses of prominent elected officials, in response to the rapid increase in measles cases in the United States in 1990. They have sought to create a network of community leaders that will act to get children immunized now and will influence legislation to ensure that children under two will be fully immunized in the future. PMID- 1408426 TI - Personalizing professional goals. AB - Goal setting is an essential step toward personal and professional freedom. If we are interested in bringing our lives into balance so that our professional goals and personal goals are integrated, we must be willing to do the necessary work of self-discovery. PMID- 1408427 TI - Sex education for adolescents with chronic conditions. PMID- 1408428 TI - A study of diagnostic reasoning in pediatric nurses. AB - PURPOSE: To examine the data collecting and interpreting phases of the diagnostic reasoning process used by practicing pediatric nurses and to determine: (a) types of information deemed important for planning nursing care; (b) the functional health patterns addressed; and (c) frequency of validation of early hypotheses. METHOD: Thirty-four registered nurses who attended continuing education pediatric nursing workshops were asked to analyze a written simulated case study discussing maternal-infant interaction. Diagnostic cues in the case study were based on a framework that consisted of a clinical nursing model of maternal-infant interaction and selected nursing diagnoses. Open-ended questions were used to examine subjects' attention to and interpretation of these cues. FINDINGS: All subjects identified information related to the child's physical needs and the mother's responsibility to meet those needs as important for planning nursing care. There was less attention given to the interaction of mother and child. The most common response was identification of cues associated with five functional health patterns (29.4% of subjects). The functional health pattern, coping-stress tolerance, was addressed least often, although all nurses identified cues associated with role relationship. Only 38% of the subjects identified the need for validation of early hypotheses. CONCLUSION: The findings support the need for further research on the diagnostic reasoning of pediatric nurses. Recommendations include methods to enhance pediatric nurses' collection and interpretation of data specific to the pediatric clinical setting. PMID- 1408429 TI - SIDS and infant positioning: implications for critical care. AB - This article will briefly review the literature that led to the AAP's recommendations of supine and side-lying positions for infants and explore the challenges and the controversy associated with changing standards and practices. It will discuss specific considerations for the critical care nurse and suggest points to consider in implementing any practice changes for seriously ill or critically ill infants. PMID- 1408430 TI - Nursing interventions aimed at reducing risks of SIDS. AB - While researchers do not fully understand the causes of SIDS, there appears to be growing consensus that SIDS is most probably a multi-etiological phenomenon. Research literature regarding the prone sleeping position as a possible risk factor for SIDS will be discussed as will proposed etiological mechanisms related to this hypothesis. Implications of this new data for pediatric nursing practice will also be examined. PMID- 1408431 TI - Childhood immunization: opportunities to improve immunization rates at lower cost. PMID- 1408432 TI - Licensure for advanced practice: be informed, be alert. PMID- 1408433 TI - The current radiologic management of intussusception: a survey and review. PMID- 1408434 TI - Intussusception reduction 1991: an international survey of pediatric radiologists. AB - A detailed survey of intussusception reduction practices at the International Pediatric Radiology '91 meeting in Stockholm yielded 78 responses from radiologists representing 21 countries on six continents. Results indicates a striking lack of conscensus on basic technical issues such as the type of contrast material or reducing agent, the pressure limits for reduction, the use of balloon-tip tubes, the role of sedation, manipulation of the abdomen during reduction, and duration of symptoms beyond which reduction would not be attempted. For example, while gas reduction has been strongly promoted in the literature during the late 1980's, only 34.7% of the respondents indicated that this was their principle choice of reducing agent. Among technique choices which produced significant correlations with outcome, it is noteworthy that pooled data suggest an eightfold increase in perforations among those using gas rather than liquid for reduction. Also, although 53.8% of respondents use parenteral sedation at least part of the time, those who reported using it regularly had significantly lower success rates than all other radiologists. This study provides a current sampling of international opinion in a subject of importance to all pediatric radiologists; and by linking the response with reported outcomes suggests opportunities for further investigation. PMID- 1408435 TI - The current radiologic management of intussusception: a survey and review. AB - To determine what practices are being utilized in the management of intussusception, a survey was sent to chairpersons of 64 Pediatric Radiology departments in the United States and Canada. There was a 92% response rate. Barium is used in 97% of departments and is the most commonly used contrast-agent in 64%. Water-soluble contrast is used in 83% of departments and air in 50%. In high-risk patients, water soluble contrast is used in 71% of departments, air in 28% and barium in 24%. Glucagon, pre-exam antibiotics, and pre-exam sedation are not used regularly in a majority of departments. The radiologic management of intussusception is more varied than only a few years ago. Use of water-soluble contrast and air have increased, while barium use is less routine. PMID- 1408436 TI - A new syndrome? Unusual facies, hooked clavicles, 13 pairs of ribs, widened metaphyses, square shaped vertebral bodies and communicating hydrocephalus. AB - Two strikingly similar twin sisters presented with characteristic facial anomalies and distinctive radiographic findings. The occurrence of this unique pattern of malformations in two sisters with unaffected parents suggests recessive inheritance. They most likely represent a previously unrecognised malformation syndrome. PMID- 1408437 TI - Subspecialization in pediatric radiology. AB - Within radiology there is an increasing trend towards specialization in North America [1]. Although some radiologists still consider themselves as generalists, every radiologist has eliminated some aspect of imaging from his repertoire [2]. Within some specialty areas of radiology further subspecialization is beginning to take place. This subspecialization is being affected by conflicting forces, some of which are pushing us towards increased subspecialization in our daily clinical work, while other forces are inhibiting such subspecialization. PMID- 1408438 TI - Cyclic direct radionuclide voiding cystography: increasing reliability in detecting vesicoureteral reflux in children. AB - The purpose of this study was to establish the sensitivity of cyclic direct radionuclide cystography (RVC) in detecting vesicoureteral reflux (VUR) in infants and small children, and to compare it to the conventional (one cycle only) RVC. 428 patients (856 renal units) were admitted to the study from January 1991 through March 1992 and all had a cyclic RVC. The age of the patients ranged from 4 months to 7 years. The overall agreement of both cycles in detecting VUR in this study was 45%, the lowest being in detecting VUR I (36%), and the highest in detecting VUR III (86%). If we had used a conventional RVC (the first cycle only), 17 (29%) VUR I, 50 (36%) VUR II and 3 (9%) VUR III, which were detected in the second cycle only, would have been missed. We conclude that cyclic RVC detected 43% more VURs than the conventional (first cycle only) RVC, and would therefore recommend its use as a standard procedure instead of the conventional RVC. PMID- 1408439 TI - Esophageal perforation by a tooth in child abuse. AB - A unique case of child abuse in a six-year-old Hispanic girl is reported. In this case, a tooth avulsed and swallowed during an episode of physical abuse and/or sexual abuse, caused an esophageal perforation resulting in a retropharyngeal abscess and mediastinal abscess containing the tooth. Although traumatic esophageal injuries in child abuse have occurred, the presence of a tooth within the mediastinal abscess is an unique manifestation of child abuse. PMID- 1408440 TI - Diagnosis of congenital antral web by ultrasound. AB - Historically, the first case of congenital prepyloric membrane in an infant was documented in 1933 [1]. Since then cases have been reported only sporadically in the literature [2-8]. This is a case of congenital antral web which was identified by real-time ultrasonography, confirmed by barium meal study, and proven at gastrotomy. PMID- 1408441 TI - Congenital hemangiopericytoma of the duodenum. AB - Hemangiopericytomas are vascular tumors of pericyte origin. Although the majority of cases have been found in adults, a small percentage have been found to be congenital, most involving the subcutaneous tissues. Gastrointestinal involvement is exceedingly rare. All of the congenital tumors were found to be benign. We report a case of congenital duodenal hemangiopericytoma in a neonate which was locally invasive. PMID- 1408442 TI - Comparison of computerized digital and film-screen radiography: response to variation in imaging kVp. AB - A controlled prospective study, in an animal model chosen to simulate portable neonatal radiography, was performed to compare the response of the Philips Computed Radiography (CR) system and conventional 200 speed film-screen (FS) to variation in imaging kVp. Acceptable images were obtained on the CR system over a very wide kVp range. In contrast the FS system produced acceptable images over a narrow kVp range. This ability suggests that the CR system should eliminate the need for repeat examinations in cases where a suboptimal kVp setting would have resulted in an unacceptable FS image. CR technology should therefore be ideally suited to portable radiography especially in situations where selection of correct exposure factors is difficult as in the neonatal nursery. PMID- 1408443 TI - Dynamic ultrafast high resolution CT findings in a case of Swyer-James syndrome. AB - In a patient with Swyer-James syndrome, the dynamic, ultrafast HRCT (DUHRCT) findings show multifocal bilateral air-trapping that was not seen on chest radiography or conventional CT scan. This technique accentuates the air trapping associated with post-infectious obliterative bronchiolitis, which is underappreciated by plain chest radiography and conventional CT. PMID- 1408445 TI - Ultrasonography of congenital muscular torticollis. AB - The sonographic appearance of the sternocleidomastoid muscles of 36 children with congenital muscular torticollis was studied. Sternocleidomastoid tumour was detected in all of them and the images were more complex than described in the literature. A patchy echo-texture was as frequent as a homogeneous echo-texture, and was more common in the younger child. The echo-genicity of the mass could be hyperechoic, isoechoic or hypoechoic relative to normal muscle. A hypoechoic rim surrounding the mass was frequently present. Change of the proportion of the mass relative to the entire muscle-mass complex in different ages matching clinical observations was also noted. These sonographic findings would be important in establishing a sonographic diagnosis. The higher sensitivity of ultrasound in detection of sternocleidomastoid tumour over clinical methods, and the importance of the sonographic findings in the management of congenital muscular torticollis were also discussed. PMID- 1408444 TI - Abdominal (liver, spleen) and bone manifestations of cat scratch disease. AB - Cat scratch disease is usually a self-limiting illness. Patients may develop systemic complications including hepatic granulomas, splenic abscesses, mesenteric adenitis, osteolytic lesions, as well as dermatologic and CNS complications. In this paper the literature is reviewed and two cases are discussed which present the imaging findings in patients with hepatic, splenic, mesenteric, and bony manifestations of cat scratch disease. PMID- 1408446 TI - Perinatal hip assessment in very low birth weight infants. AB - Fifty healthy low birth weight infants (less than 1500 g) without risk factors for congenital hip dysplasia (CHD) were examined by ultrasonography (100 hips) at 40 weeks corrected age and controlled at 3 months postnatal age. Sonographic assessment was performed using the classification of Graf. A physiological delay of hip maturation was observed in 10% of the patients (type IIa). At follow-up all of them had normal hip morphology without any pathological finding. Our results suggest that prematurity alone should not be considered a risk factor for CHD. PMID- 1408447 TI - Occipital horn syndrome. Additional radiographic findings in two new cases. AB - Occipital horn syndrome, a rare genetic disorder of copper metabolism, was recognized in 2 unrelated patients. Radiographs of these patients at various ages allowed confirmation of previously described radiographic findings. In addition, new radiographic manifestations were encountered. These pathognomonic radiographic findings are presented and the clinical and biochemical features of occipital horn syndrome are reviewed. PMID- 1408448 TI - Dysplastic gangliocytoma (Lhermitte-Duclos disease): CT and MR imaging. AB - Dysplastic gangliocytoma (Lhermitte-Duclos disease) is a rare entity. Usually presenting as a posterior fossa mass, dysplastic gangliocytoma is not a true neoplasm but a hard-to-characterize lesion that may represent an abnormality of cell migration or a phacomatosis. Previous reports of CT findings are rare in the radiologic literature, and high-field (1.5 Tesla) MR images have never been described in the pediatric age group. We present a case of dysplastic gangliocytoma in a one-year-old boy with CT and MR findings. PMID- 1408449 TI - Color flow imaging in children with clinically suspected testicular torsion. AB - 32 boys with symptoms of an acute scrotum had testicular sonography with color flow imaging (CFI). Patients ranged in age from 4-15 years (avg = 11 yrs). Symptoms were present from 12 h to 5 days (avg = 42 hrs). CFI correctly predicted presence or absence of testicular perfusion in 11 boys who had surgical exploration of the scrotum. 8 of these 11 patients had hemorrhagic infarction of the testicle, 1 had torsion of the appendix epididymis, 1 had epididymitis, and 1 had bilateral incomplete torsions with normal testicular perfusion. The remaining 21 patients did not have an operation. At least a 1 year follow-up of all patients has shown no clinical evidence of testicular atrophy to suggest a missed diagnosis of torsion. Absence or markedly decreased testicular flow was easily identified and indicates testicular ischemia/infarction. Conversely, hyperemia of the testis and/or epididymis is usually associated with trauma or infection. However, incomplete torsion or spontaneous detorsion may demonstrate normal testicular flow on CFI. Only close correlation of clinical symptomatology and gray scale findings with CFI can identify these patients, who remain at high risk for subsequent complete torsion and infarction. PMID- 1408450 TI - Juvenile xanthogranuloma: non-X histiocytosis with systemic involvement. AB - Two patients with different patterns of soft tissue and bone involvement demonstrate the variability of extracutaneous manifestations of juvenile xanthogranuloma, a non-X histiocytosis, better known to dermatologists than to radiologists. PMID- 1408451 TI - Juvenile xanthogranuloma with extracutaneous lesions. AB - The purpose of this article is to present a case of juvenile xanthogranuloma with pulmonary, retroperitoneal and splenic involvement. The similar echographic pattern of the cutaneous and visceral lesions was very helpful in order to suggest the correct diagnosis. PMID- 1408452 TI - Neonatal phrenic nerve paralysis resulting from intercostal drainage of pneumothorax. AB - Four cases of phrenic nerve paralysis complicating chest tube placement in the newborn for pneumothorax are presented. This complication is related to abnormal location of the medial end of the chest tube. It is suggested that on the frontal chest radiograph, the medial end of the chest tube should be no less than 1 cm from the spine. PMID- 1408453 TI - MRI of sequela of transverse myelitis. AB - A 4-year-old boy developed acute paraplegia, associated with sensory impairement and bowel and urinary dysfunction after an URI. MRI showed diffuse hyperintensity in T2WI in the spinal cord below the T6 level. Acute transverse myelitis was diagnosed based on the clinical presentations and MRI findings. The patient had poor recovery and two months later, a follow-up MRI disclosed a severe diffuse atrophic change of the spinal cord in the affected segment. PMID- 1408454 TI - An unusual presentation of urogenital rhabdomyosarcoma (sarcoma botryoides) in a Nigerian child. AB - A 5-year-old child who presented with what was diagnosed clinically as posterior urethral valve and radiologically as multiple urethral and vesical polyps is described. This lesion was found on histological investigation to be a rhabdomyosarcoma (sarcoma botryoides). PMID- 1408455 TI - Obstruction of cerebral arteries in childhood stroke. AB - Middle cerebral artery obstruction in children is reviewed by our two cases. Ischemic childhood stroke was caused by moyamoya disease in the first, and by fibromuscular dysplasia in the second patient. In both cases transcranial Doppler sonography and cranial CT were performed, but the final diagnosis was made by angiography. The importance of angiography in childhood stroke is emphasized. PMID- 1408456 TI - Solitary ivory vertebra due to primary Ewing's sarcoma. AB - Dense sclerosis of most of the vertebral body has been termed as "ivory vertebra". While this condition occurs rather frequently in adults it is not found very often in children. PMID- 1408457 TI - Juvenile gout with typical radiographic findings. AB - Gout, a common disorder in adults is exceedingly rare in the first decade of life and uncommon in teenagers. A recent book on bone diseases in childhood does not even mention gout [7]. Childhood podagra with a radiographic findings is a very unusual finding indeed. PMID- 1408458 TI - Amyloid goiter in a child--US, CT and MR evaluation. AB - There are few radiological descriptions of amyloid goiter, basically in adult patients of oriental origin. We present a ten-year-old boy with Still's disease and secondary thyroid amyloidosis, describing the US, CT and MR findings. PMID- 1408459 TI - Laryngotracheo-bronchial cartilage calcification in children. PMID- 1408460 TI - Development of the human antibody repertoire. PMID- 1408461 TI - A role for tumor necrosis factor-alpha and interferon-gamma in the regulation of interleukin-4-induced human thymocyte proliferation in vitro. Heightened sensitivity in the Down syndrome (trisomy 21) thymus. AB - The influence of recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF) on IL-4-induced proliferation of postnatal human thymocytes from eight children with Down syndrome (DS, trisomy 21) and 18 control children was evaluated. DS thymuses were studied because they are characterized by cortical depletion and abnormal thymocyte differentiation. IL-4, without mitogen, induced a dose-dependent proliferation of both DS and control thymocytes. The proliferation was comparable to that induced by IL-2 and far greater than the proliferation mediated by IL-1 beta in the absence of mitogen. The level of IL-4 responsiveness correlated with the proportion of cells expressing the gamma, delta chains of the T cell receptor. Furthermore, thymocyte preparations greatly enriched for T cell receptor gamma, delta-bearing cells were found to vigorously proliferate when treated with IL-4. Both IFN-gamma and TNF inhibited IL-4-driven proliferation in a dose-dependent manner, but DS thymocytes were found to be significantly more sensitive to inhibition by both cytokines. Our studies suggest an important role for IL-4 in the proliferation of T cell receptor gamma, delta+ thymocytes and demonstrate regulatory functions for IFN-gamma and TNF in human thymocyte proliferation. The increased sensitivity of DS thymocytes to IFN-gamma and TNF may explain anatomical abnormalities in DS thymuses and suggests the involvement of genes encoded on human chromosome 21 in the responses to both IFN gamma and TNF. PMID- 1408462 TI - Enhanced response of human circulating erythroid progenitor cells to hGH and to IGF-I in children with insufficient growth hormone secretion. AB - The response of hematopoietic progenitors to the growth promoting effects of hGH and IGF-I has been documented. In this study, the effects of recombinant hGH and IGF-I on the growth of circulating erythroid burst forming cells (BFU-E) from growth-IGF-I retarded children with insufficient growth hormone secretion (IGHS) were evaluated and compared with values obtained from either children with short stature and normal growth hormone levels (SNGH) or normal donors. Both recombinant hGH and IGF-I had significantly greater stimulatory effects on the growth of BFU-E from the IGHS compared with the SNGH and with the normally growing children. At its optimal concentration of 200 micrograms/L, recombinant hGH had a stimulatory effect on the growth of BFU-E from 11 IGHS children yielding a mean +/- SD value of 2.0 +/- 0.3-fold above the unstimulated controls compared with 1.45 +/- 0.16-fold and 1.36 +/- 0.04-fold stimulation of BFU-E from six SNGH and five normal donors, respectively. Similarly, IGF-I, at its optimal concentration of 0.065 nmol/L (0.5 ng/mL), stimulated IGHS-derived BFU-E growth 1.67 +/- 0.25-fold above unstimulated controls, compared with 1.28 +/- 0.17-fold and 1.3 +/- 0.1-fold stimulation of BFU-E from SNGH and from normal donors, respectively. The hGH- and IGF-I-induced stimulatory effects could be neutralized by their respective specific MAb.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408463 TI - Elevated growth hormone secretory rate in premature infants: deconvolution analysis of pulsatile growth hormone secretion in the neonate. AB - Premature infants have higher circulating concentrations of growth hormone (GH) than term infants. Previous investigations of these differences have used sampling frequencies of every 30 min with subsequent application of pulse detection algorithms, such as the CLUSTER program, to assess serum GH pulse parameters. To determine differences in GH secretory rates or GH t1/2 values between premature and term infants, we have sampled 11 neonates at 15-min intervals. We performed deconvolution analysis of the resultant plasma GH values to estimate GH secretory and clearance parameters. Five premature infants (gestational age range 24-34 wk) and six term infants (gestational age range 38 42 wk) were sampled every 15 min for 6 h. All subjects had indwelling arterial catheters. GH was measured (in duplicate) by RIA using 10 microL of plasma. Premature infants had higher secretory burst amplitudes (2.2 +/- 0.13 micrograms/L/min versus 1.4 +/- 0.27 micrograms/L/min, p = 0.02), higher production rates (product of the total number of bursts and the mean mass of GH secreted per burst, 811 +/- 173 micrograms/L/6 h versus 283 +/- 77 micrograms/L/6 h, p = 0.03), and a higher mass of GH per secretory burst (106 +/- 25 micrograms/L versus 38 +/- 11 micrograms/L, p = 0.049) than term infants. The integrated plasma GH concentration exhibited a strong trend toward a higher value in the premature infants (18,100 +/- 800 micrograms/L versus 10,200 +/- 2,700 micrograms/L, p = 0.067).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408464 TI - Changes in IGF-I and -II, IGF binding protein, and IGF receptor transcript abundance after uterine artery ligation. AB - Altered IGF activity may be one mechanism involved in the pathogenesis of intrauterine growth retardation (IUGR). We assessed the expression of IGF, IGF binding protein (IGFBP), and IGF receptor transcripts in liver, carcass, and placenta of fetal rats with IUGR resulting from unilateral uterine artery ligation. We found that uterine artery ligation on d 17 of gestation resulted in reduced body weight, liver weight, and placental weight on d 20 in the fetuses from the ligated uterine horn (UA-lig) compared with those from the opposite, nonligated uterine horn (UA-nonlig) and those from dams with no surgery or anesthesia. As assessed by solution hybridization, UA-lig fetuses exhibited significantly higher hepatic IGFBP-1, IGFBP-2, and IGF-II transcript abundance than UA-nonlig controls (increased 110, 50, and 31%, respectively). The only major difference among groups in carcass and placenta mRNA abundance was a 44% decrease in placental IGF-II expression in UA-lig pups compared with pups from dams that had had no surgery or anesthesia. Serum IGFBP, analyzed by ligand blot, showed a 2.4-fold increase in the doublet IGFBP-1/-2 band in UA-lig fetuses. Serum immunoreactive IGFBP-2 was unchanged among the groups, indicating that IGFBP-1 accounted for the increase in doublet intensity. Our results suggest that increased serum IGFBP-1 concentrations may decrease IGF activity in serum and thus inhibit IGF-stimulated cell proliferation or, by crossing the endothelial border, inhibit the activity of locally produced IGF. Decreased IGF-II expression in placenta also may contribute to decreased placental growth and, in turn, to IUGR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408465 TI - Destripeptide insulin-like growth factor-I in milk from bovine somatotropin treated cows. AB - Total somatomedins from milk of bovine somatotropin-treated cows were isolated and characterized to determine the relative amount of the three amino acid N terminally truncated form of IGF-I (destripeptide IGF-I). The somatomedin fraction was isolated using organic solvent and solid-phase extractions followed by preparative reverse phase HPLC and affinity chromatography. The overall yield of IGF-I was 28%, and destripeptide IGF-I was recovered with similar efficiency. The isolated somatomedins were resolved by capillary zonal electrophoresis and identified using recombinant somatomedin standards. The concentration of destripeptide IGF-I relative to full length IGF-I was determined by amino terminal sequencing and by bioassay. Results from these experiments indicated that the level of destripeptide IGF-I in milk from somatotropin-treated cows was less than 3% of the IGF-I concentration. Destripeptide IGF-I is therefore a minor component of the somatomedins present in milk from treated cows and does not contribute significantly to the proliferative activity of this milk. PMID- 1408466 TI - Early dietary antigens delay the development of gut mucosal barrier in preweaning rats. AB - To determine the effects of early antigen exposure on the maturation of the gastrointestinal mucosal barrier, rat pups were divided into three groups at the age of 14 d. In addition to normal maternal milk, group CM (n = 24) received daily a gavage feed of cow's milk and group PH (n = 20) a whey protein hydrolysate during the experimental feeding period (14-20 d). Controls (n = 15) remained on maternal milk only. At 21 d, when "gut closure" normally occurs, intestinal absorption of horseradish peroxidase (HRP), was examined in vitro in Ussing chambers. The absorption of intact HRP [geometric mean (95% confidence interval)] was significantly higher in group CM [35.3 (16.7, 74.7) ng.h-1.cm-2] than in group PH [5.2 (1.4, 19.5) ng.h-1.cm-2] and in controls [3.4 (0.8, 15.1) ng.h-1.cm-2; F = 5.54, p = 0.006]. The absorption of degraded HRP was comparable in all groups. There were no modifications in electrical parameters in association with increased mucosal permeability to HRP. Furthermore, in group CM electron-microscopic studies disclosed accumulation of HRP in the cytoplasm of the epithelial cells and in the intercellular spaces where cell junctions remained unaltered. These results indicate that early administration of antigens delays the process of gut closure. They further suggest that continuously enhanced endocytosis of macro-molecules is induced by an insult to the mucosa as part of the host response to these antigens, irrespective of the protection afforded by maternal milk. PMID- 1408467 TI - Synergistic effects of thyroxine and dexamethasone on enzyme ontogeny in rat small intestine. AB - The synergistic effects of dexamethasone (DEX) and thyroxine (T4) on the postnatal maturation of the 13-d-old rodent small intestine has been studied. Previous studies have shown that hydrocortisone and T4 produced a synergistic response in enzyme maturation. However, T4 elevates corticosteroid-binding globulin, which reduces the clearance of hydrocortisone. Thus, the apparent synergy between T4 and hydrocortisone may have been due to increased glucocorticoid availability. DEX, which does not bind to corticosteroid-binding globulin, was given (d8-12) at 25 pmol (i.e. 0.01 micrograms)/g body wt/d as established by a dose-response study in which this dose of DEX induced one third the maximum response in sucrase activity. In this way, synergy with T4 (130 pmol/g body wt/d, i.e. 0.1 micrograms/g body wt/d, d 5-12) could still be observed. Glucoamylase, lactase, acid beta-galactosidase, alkaline phosphatase, and sucrase activities were determined in two regions of the small intestine. Overall, the results for the two hormones administered alone showed intestinal maturation to be not significantly affected in the T4 group and partially stimulated in the DEX group. When combined, DEX + T4 synergistically increased jejunal sucrase, ileal glucoamylase, and duodenal alkaline phosphatase, and lowered ileal acid beta-galactosidase. The striking exceptions to the general pattern were two brush border enzymes that normally decline during intestinal maturation, namely ileal alkaline phosphatase and jejunal and ileal lactase. For these enzymes, DEX alone did not elicit precocious maturation, and there was no evidence for a synergistic interaction of these two hormones. Serum corticosterone concentrations also were measured. When corticosterone concentrations were compared with enzyme activity, no correlation was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408468 TI - Enterohepatic distribution of carnitine in developing piglets: relation to glucagon and insulin. AB - L-Carnitine plays a crucial role in the perinatal transition from carbohydrate to lipid-derived energy. To examine the potential contribution of assimilated dietary carnitine to the elevated hepatic concentrations in newborns, we measured carnitine concentrations in sow milk, jejunum, and liver, and in vitro jejunal carnitine transport in piglets aged 1-36 d. Hepatic and sow milk total carnitine concentrations peaked soon after birth and declined with age (p = 0.035 and 0.026, respectively). Although jejunal total carnitine concentrations remained stable, jejunal carnitine flux was higher at 2 d of age than in older piglets. To examine the possible signals that regulate hepatic carnitine, portal enteroinsular hormones were measured by RIA. Portal glucagon (p = 0.0006), insulin (p = 0.0001), and glucagon:insulin ratio (p = 0.037) were related to age. Portal glucagon was highest in newborns and during weaning, whereas insulin increased progressively with age; the portal glucagon:insulin ratio, like hepatic carnitine, peaked soon after birth and fell with age. A multiple regression analysis indicated a positive association between glucagon and hepatic carnitine and a negative one between insulin and hepatic carnitine (R = 0.802, p = 0.001). An overall pattern of elevated dietary carnitine levels and increased small intestinal absorption and hepatic accumulation of carnitine is noted in early development. The finding of a similar pattern in glucagon-to-insulin ratio suggests that both hormones may participate in the regulation of enterohepatic carnitine distribution in newborns. PMID- 1408469 TI - Carrier-mediated beta-D-hydroxybutyrate transport in brush-border membrane vesicles from rat placenta. AB - Carrier-mediated beta-D-hydroxybutyrate transport in brush-border membrane (maternal-sided) vesicles prepared from trophoblast rat placenta was studied. The existence of a carrier-mediated transport system for beta-D-hydroxybutyrate in brush-border membrane vesicles was substantiated by the strong inhibitory effect of the protein modifier p-chloromercuriphenyl sulfonic acid and by the saturability of beta-D-hydroxybutyrate uptake as a function of beta-D hydroxybutyrate concentration. beta-D-hydroxybutyrate uptake was stimulated by the presence of an inward-directed proton gradient but not by an inward-directed Na+ gradient. The mechanism for transport of beta-D-hydroxybutyrate seems to be a beta-D-hydroxybutyrate/H+ symport and not a beta-D-hydroxybutyrate/OH- antiport because beta-D-hydroxybutyrate transport was not sensitive to 4,4-diisothiocyano 2,2'-stilbenedisulfonic acid or furosemide. The Km, Vmax, and kd calculated by applying the iteration procedure to the data were 16 mM, 58 nmol.mg-1.10 s-1, and 0 nL.mg-1.s-1, respectively. The beta-D-hydroxybutyrate transport system might be shared by other monocarboxylic acids, and the carrier shows reversibility and exchange properties. There were no significant changes in the kinetic parameters of the beta-D-hydroxybutyrate transport system during the last 3 d of gestation. Nevertheless, there was a significant increase in the capacity of the beta-D hydroxybutyrate transport system in brush-border membrane vesicles prepared from fasted pregnant rats, suggesting that the rise in maternal ketone body levels occurring as a consequence of maternal starvation is concurrent with the stimulation of the activity of the beta-D-hydroxybutyrate placental carrier to supply the fetus with ketone bodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408470 TI - Tin-protoporphyrin-mediated disruption in vivo of heme oxygenase-2 protein integrity and activity in rat brain. AB - The ability of synthetic metalloporphyrins to suppress heme oxygenase activity and bilirubin formation has recently become of considerable clinical and experimental interest for suppression of jaundice in humans, including neonatal hyperbilirubinemia. The present investigation compares the biochemical effects of Sn- and Zn-protoporphyrins on the predominant heme oxygenase isozyme present in the brain (HO-2) at activity, protein, and transcript levels and describes the ability of Sn-protoporphyrin to adversely affect this isozyme. Specifically, 6 h after a modest dose (50 mumol/kg, i.v.) of Sn-protoporphyrin, heme oxygenase activity in rat brain was nearly undetectable. In addition, as revealed by Western blot analysis, HO-2 protein level was decreased by 20% and the electrophoretic behavior of the protein in the microsomal membranes was altered. Moreover, the activity of NADPH-cytochrome P-450 reductase, which is required for the oxidation of heme molecule, was markedly decreased (60% of control). Western immunoblot analysis revealed also a pronounced decrease in the reductase protein level. The inducible form of heme oxygenase, HO-1, was not detectable by immunoblotting in brain microsomes of either control or Sn-protoporphyrin-treated animals. Northern blot analyses did not reveal decreases in the levels of the single HO-1 mRNA (1.8 kb) or the two HO-2 transcripts (1.3 and 1.9 kb), suggesting that Sn-protoporphyrin mediates its effects on heme oxygenase isozymes at the protein level. Zn-protoporphyrin, on the other hand, had no deleterious effect on brain parameters presently investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408471 TI - Caffeine decreases zinc and metallothionein levels in heart of newborn and adult rats. AB - The purpose of the present study is to show that dietary caffeine, heart tissue Zn levels, and metallothionein (MT) concentration are all interrelated in newborn rats. Dams with eight pups in the control group were fed a 20% protein diet upon delivery, whereas dams in the experimental group were fed a 20% protein diet supplemented with caffeine (2 mg/100 g body weight). Offspring were killed at d 22 postbirth and the hearts and livers were removed to determine the Zn and MT concentrations. Hearts of the newborn rats in the caffeine group showed decreased Zn levels as well as decreased MT concentration. To explain the observed effects in newborn rats, the relationship between Zn and MT levels was studied in adult female rats. They were injected intraperitoneally with either ZnCl2 (20 mg/kg body weight) dissolved in saline solution or ZnCl2 and caffeine (4 mg/kg body weight) over a period of 2 d. Injection of ZnCl2 into adult female rats resulted in an increase in heart MT levels, whereas injection of caffeine caused decreased Zn levels and MT concentration. Current findings indicate that dietary caffeine intake during the lactational period by newborn pups causes a decrease of the heart Zn and MT levels. PMID- 1408472 TI - Analysis of dynamic atrial dimension and function during early cardiac development in the chick embryo. AB - Although atrial morphologic changes are well documented, the description of early atrial function is limited. We used videomicroscopic methods to define the function of the contracting atrium in stage 16 to 24 white Leghorn chick embryos. We exposed the embryo in ovo (right side up) and imaged the ventricle, then repositioned the embryo (left side up) and imaged the atrium (n greater than or equal to 8 per stage). We traced the atrial endocardial border and then measured atrial perimeter (mm) and cross-sectional area (mm2). A 20-MHz pulsed Doppler velocity meter was used to measure atrioventricular blood velocity during atrial imaging in an additional six stage 21 embryos. Data were tested by analysis of variance and regression analysis. Mean heart rate change after repositioning was 4 +/- 1%. Atrial maximum and minimum area increased linearly versus embryo stage (y = 0.10x - 1.41, r = 0.89, p less than 0.05 and y = 0.05x - 0.67, r = 0.82, p less than 0.05, respectively). Shortening fraction (percentage of reduction) of atrial perimeter and area decreased from 32.3 +/- 2.0% to 27.5 +/- 1.8% (p less than 0.05) and 56.2 +/- 3.0% to 47.7 +/- 2.0% (p less than 0.05), respectively, from stage 16 to 24. During atrial contraction, the velocity of circumferential wall shortening increased linearly with stage (y = 0.22x - 2.08, r = 0.81, p less than 0.01); however, the velocity of lengthening was similar between stages (p = 0.45). Simultaneous atrial imaging and pulsed Doppler velocity measurement showed that passive atrioventricular flow occurred late in atrial lengthening and active atrioventricular flow occurred during atrial contraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408473 TI - Recognition of a fetal subdiaphragmatic venous vestibulum essential for fetal venous Doppler assessment. AB - Ultrasonic visualization of the human fetal subdiaphragmatic area demonstrated anatomical relationships, different from descriptions in the literature. Four human fetal postmortem specimens at 18, 26, 28, and 34 wk of gestation were examined to ascertain morphologic details of intra- and perihepatic vasculature. Drawings of these dissected preparations were compared with ultrasonic images from the same region. With both methods the presence of a venous vestibulum immediately proximate to the diaphragm could be demonstrated. The abdominal inferior vena cava ends in a funnel-like structure, which also contains the orifices of the hepatic veins, the ductus venosus, and a phrenic vein. A considerable variability in Doppler flow recordings could result from blood propelling out of these various vessels into the vestibulum. It is, therefore, suggested that information on blood-flow velocities in venous hepatic vessels should be obtained more distally in the separate vessels and not at the entrance into the right atrium. PMID- 1408474 TI - Arterial oxygen tension threshold range for the onset of arousal and breathing in fetal sheep. AB - Mechanisms for the control of episodic fetal breathing movements or the onset of continuous breathing at birth remain unknown. Lung distension with 100% O2 at a continuous positive airway pressure of 30 cm H2O may induce arousal and continuous breathing. To investigate 1) the threshold range of arterial oxygen tension (PaO2) for the onset of arousal and breathing and 2) the graded response of breathing to various levels of PaO2, we studied 10 fetal sheep between 135 and 142 d of gestation (term = 147 +/- 2 d). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, arterial pH, and blood gas tensions. PaO2 threshold was determined through an indwelling O2 sensor catheter. Fetal lungs were distended at a continuous positive airway pressure of 40 cm H2O with 100% N2 or with O2 ranging from 40 to 100% via an in situ endotracheal tube. At the onset of arousal (n = 10), PaO2, arterial carbon dioxide tension, and Hb O2 saturation increased from control values of 21.7 +/- 0.75 torr (2.9 +/- 0.09 kPa), 41.8 +/- 1.1 torr (5.47 +/- 0.15 kPa), and 52.9 +/- 2.6% to 65.6 +/- 9.6 torr (8.74 +/- 1.28 kPa), 46.9 +/- 1.3 torr (6.25 +/- 0.17 kPa), and 92.9 +/- 2.06%, respectively, whereas the pH decreased from 7.31 +/- 0.006 to 7.27 +/- 0.009 (mean +/- SEM; p = 0.001, 0.04, 0.002, and 0.001, respectively). Seven of 10 fetuses breathed continuously. In these fetuses, PaO2 and arterial carbon dioxide tension further increased and pH decreased; however, no further significant increase in Hb O2 saturation was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408475 TI - Increased respiratory drive and limited adaptation to loaded breathing in bronchopulmonary dysplasia. AB - Ventilatory parameters and respiratory drive with and without an added acute resistive load were assessed in 11 healthy preterm infants and 11 infants with bronchopulmonary dysplasia (BPD). Lung mechanics (breathing frequency, tidal volume, minute ventilation, compliance, and resistance) were determined with esophageal manometry and pneumotachography. Respiratory drive was assessed by determining the airway pressure measured 100 ms after the onset of an inspiratory effort against an occlusion. Infants were studied at baseline and with an external inspiratory resistive load of 213.7 cm H2O/L/s. Infants with BPD had similar breathing frequency, tidal volume, and minute ventilation, lower compliance, and greater resistance and airway pressure at 100 ms than healthy preterm infants at rest. With loading, healthy preterm infants demonstrated increased airway pressure at 100 ms, whereas infants with BPD showed no change. Although the healthy preterm infants had decreased minute ventilation and tidal volume with loading, decreases in ventilation were greater in the infants with BPD. These data demonstrate that infants with BPD have responded to a chronic intrinsic load with increased drive. However, this may result in decreased ventilatory reserve and hence, a limited ability to adapt to acute pulmonary loads. PMID- 1408476 TI - Antioxidant defense mechanisms of endothelial cells and renal tubular epithelial cells in vitro: role of the glutathione redox cycle and catalase. AB - We recently demonstrated that endothelial cells are more susceptible than renal tubular epithelial cells to oxidant injury and that renal tubular epithelial cells with proximal tubular characteristics including porcine proximal tubular epithelial cells, opossum kidney proximal tubular epithelial cells, and normal human kidney cortical epithelial cells are more susceptible to oxidant injury than the distal nephron-derived Madin Darby canine kidney cell line. To determine the basis of this differential response, we evaluated several antioxidant defenses in the five cell lines. Glutathione levels were not significantly different among the five cell lines, but catalase and glutathione reductase levels were significantly (p less than 0.01) lower in endothelial cells compared to all renal tubular epithelial cells. Among renal tubular epithelial cells, Madin Darby canine kidney cells had significantly (p less than 0.05) higher glutathione peroxidase activity. To further evaluate the role of antioxidant defenses in limiting oxidant injury, we determined two responses to oxidant injury (ATP depletion and 51Cr release) when glutathione was depleted with buthionine sulfoxamine and when catalase was inhibited with aminotriazole. Oxidant-induced ATP depletion was accentuated when catalase was inhibited as well as when glutathione was depleted with buthionine sulfoxamine. In contrast, inhibition of catalase had little or no effect on 51Cr release, whereas glutathione depletion resulted in accentuated 51Cr release. We conclude that the increased susceptibility of endothelial cells to oxidant injury as compared with epithelial cells is associated with lower antioxidant defenses. Disruption of the glutathione redox cycle results in accentuated ATP depletion and lytic injury, whereas inhibition of catalase results in accentuated ATP depletion with little effect on lytic injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408477 TI - The effect of monosaturated and polyunsaturated fatty acids on oxygen toxicity in cultured cells. AB - The influence of oleic, linoleic (LIN), and eicosapentaenoic (EPA) acids incorporated into cellular lipids on susceptibility to O2-induced toxicity was evaluated in Chinese hamster fibroblasts (HA1) using a clonogenic cell survival assay. Fatty acid incorporation was achieved by incubating HA1 cells in 21% O2 for 72 h in the presence or absence of media supplemented with 25 microM oleic acid, 25 microM LIN, or 2, 4, and 25 microM EPA. This fatty acid incorporation period increased the percentage of composition in phospholipids 2-fold for oleic acid, 6-fold for LIN, and 6- to 20-fold for EPA. Vitamin E, total glutathione, superoxide dismutase activity, glutathione transferase activity, and catalase activity were unchanged, relative to control, in the 25-microM EPA-treated group, and only total glutathione was elevated in the LIN-treated group. After the incorporation period, the cells were placed in non-fatty acid supplemented media and exposed to 95% O2, and clonogenic survival responses were evaluated at time intervals up to 100 h. Sensitization to O2 toxicity in EPA-treated cells was apparent after 24 h of O2 exposure, whereas LIN-treated cells were significantly (p less than 0.05) sensitized to hyperoxia after 54 h of exposure, indicating that EPA was a more potent sensitizer for O2 injury. Furthermore, cells supplemented with 4 and 25 microM EPA were more sensitive to O2 toxicity than cells supplemented with 2 microM EPA. In contrast, cells treated with 25 microM oleic acid were significantly more resistant to O2 toxicity at 51, 72, and 98 h of O2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408478 TI - Long term efficacy of hepatitis B vaccine in infants born to hepatitis B e antigen-positive mothers. AB - The long term protective efficacy of recombinant hepatitis B vaccine, administered alone or concomitantly with hepatitis B immunoglobulin, was assessed in 263 healthy neonates of hepatitis B e antigen-positive mothers. Infants received the first dose of vaccine at birth; additional doses were given at either Months 1, 2 and 12 or Months 1 and 6. During the follow-up period, which ranged from 2 to 4 years, protective titers (> or = 10 mIU/ml) of anti-hepatitis B surface antibodies were found in virtually all infants who had responded to the primary course of vaccination. "Natural boosts," without persistent infection, were observed in only a small number of children. All children who were shown to have become chronic carriers were infected within the first year of life. No statistical difference in long term protective efficacy could be shown between the two vaccination schedules used or between the use of vaccine alone or vaccine plus hepatitis B immunoglobulin for either schedule. PMID- 1408479 TI - Comparison of high titer Edmonston-Zagreb, Biken-CAM and Schwarz measles vaccines in Peruvian infants. AB - In an effort to identify the optimal dose and strain of measles vaccination for early immunization, Peruvian infants were randomly assigned to receive one of three measles vaccines in varying doses at 5 to 6 or 8 to 9 months of age. Edmonston-Zagreb vaccines were significantly (P < 0.001) more immunogenic than equivalent or higher titers of Schwarz or Biken-CAM vaccines as determined by neutralization antibody response 3 months after vaccination. Eighty-two percent of infants who received high titer Edmonston-Zagreb vaccine at 5 to 6 months of age developed protective concentrations of measles antibody, a response rate similar to that observed after standard titer Schwarz (81%) or high titer Biken CAM vaccine (81%) at 8 to 9 months of age. No significant differences in the rates of fever, rash or other adverse events were noted by vaccine group 10 to 14 days after vaccination. Although the high titer vaccines are more immunogenic in young infants than standard vaccines, long term safety must be assured before these vaccines can be put into widespread use. PMID- 1408480 TI - Serum adenosine deaminase in the early diagnosis of typhoid fever. AB - To study the usefulness of the enzyme adenosine deaminase for the early diagnosis of typhoid fever, its activity in serum was assayed in 277 children admitted to the Hospital Guillermo Grant Benavente at Concepcion, Chile, from March, 1988, to December, 1990. The children were distributed into seven groups: control, N = 82; bacteremia, N = 8; acute viral respiratory infection, N = 43; febrile children with miscellaneous etiologies, N = 49; pulmonary tuberculosis, N = 3; hepatitis A virus infection, N = 30; and typhoid fever, N = 62. The medium serum adenosine deaminase values were significantly higher in children with typhoid fever (P < 0.0001) in relation to the values in the control group (122.2 +/- 40.7 vs 28.1 +/ 8.4 units/liter at 37 degrees C). This test had a sensitivity of 91.9% and a specificity of 92.5% in identifying the patient with typhoid fever when using 80 units/liter as the cutoff values. The positive predictive value of the test was 83.8% and the negative predictive value was 96%. Determination of adenosine deaminase values in serum could be helpful in the early diagnosis of typhoid fever. PMID- 1408481 TI - Intermediate resistance of Streptococcus pneumoniae to penicillin in children in day-care centers. AB - This study was performed to determine the prevalence, serotypes and antibiotic susceptibility patterns of penicillin-resistant Streptococcus pneumoniae in children younger than 3 years of age in day-care centers in Houston, TX. Nasopharyngeal cultures were obtained on two occasions, in March and May, 1989, from 140 children in 4 day-care centers. All penicillin-resistant S. pneumoniae organisms isolated in this study had minimum inhibitory concentrations to penicillin of between 0.1 and 0.5 microgram/ml and were thus intermediately resistant. No highly resistant S. pneumoniae (minimum inhibitory concentration > or = 1.0 microgram/ml) was isolated in this study. Nasal carriage of S. pneumoniae occurred in 39% of children; carriage of intermediately resistant S. pneumoniae occurred in 4% of children. Of the 39% of children who carried S. pneumoniae, 11% carried intermediately resistant strains. In one day-care center with a prior history of intermediately resistant S. pneumoniae (Center 1), the prevalence of intermediate penicillin resistance was significantly (P = 0.047) higher than in the other three centers. Among children surveyed twice 15% of Center 1 children carried an intermediately penicillin-resistant strain at least once, whereas in the other centers 3% of children carried an intermediately resistant strain at least once. Sixty-two percent of intermediately penicillin resistant strains were resistant to multiple antibiotics and all were serotype 14. Intermediately penicillin-resistant S. pneumoniae isolates were prevalent among young children in day-care centers in Houston and may persist in some day care centers and become endemic. PMID- 1408482 TI - Risk factors associated with severe measles in Puerto Rico. AB - From January to April, 1990, 695 measles cases were reported to the Puerto Rico Health Department; there were 12 measles-associated deaths (case fatality ratio, 17/1000), more than in any year since 1967. We conducted a case-control study of risk factors for severe measles. We identified 16 children (ages 5 to 34 months) with severe measles and selected children with nonsevere measles as controls (39 hospitalized and 38 nonhospitalized). Controls were frequency matched to severe measles cases by region of residence. One case and two controls had been vaccinated. An underlying illness was present in 50% of cases and 16% of nonhospitalized controls (Mantel-Haenszel weighted odds ratio 5.3; 95% confidence interval 1.4, 20.2). In a multivariate analysis cases were significantly more likely than hospitalized controls to be from families with an annual income of < $5000 (odds ratio (OR), 26.9), to have a mother without a high school degree (OR 11.1), to be anemic (hemoglobin < 10 g/dl) (OR 15.9) and have an underlying illness (OR 18.3). During measles outbreaks preventing severe illness requires aggressive control measures and strategies to increase vaccine coverage of children with underlying illnesses and of low socioeconomic status. PMID- 1408483 TI - Epidemiology of measles in the United States in 1989 and 1990. AB - During 1989 and 1990 measles incidence increased sharply in the United States. We compared cases reported during these years with those reported between 1981 and 1988. Incidence increased 462% in 1989, and incidence in 1990 (11.2/100,000) was the highest in more than a decade. Although all ages were affected the greatest increases were in children < 5 years and in adults. Incidence was 7- to 10-fold higher among racial/ethnic minority preschoolers than whites, and 80% of vaccine eligible preschool age cases were unvaccinated. Complications occurred in 9418 (20.5%) cases, most frequently in young children and adults. Large urban outbreaks affecting predominantly unvaccinated preschoolers were common; 47% of all cases reported in 1990 were associated with 5 outbreaks. Reasons for the increased incidence are not clear. Current information suggests no change in vaccination coverage among preschool age children or in vaccine efficacy. Continued surveillance and evaluation of epidemiologic and laboratory data are necessary. The most pressing need is to improve age-appropriate vaccination among preschool age children. PMID- 1408484 TI - Respiratory tract colonization with Ureaplasma urealyticum and bronchopulmonary dysplasia in neonates in southern Israel. AB - Ureaplasma urealyticum has been recognized as an important potential pathogen in premature neonates. Reported rates of colonization of the respiratory tract vary. Data on neonatal ureaplasma colonization outside the United States and Western Europe are rare. Therefore we prospectively studied nasopharyngeal and endotracheal colonization in a cohort of 114 preterm and 100 full term infants within 48 hours of birth. The colonization rate was 24% in the premature infants and zero in the full term infants. Bronchopulmonary dysplasia developed in 19% of infants with nasopharyngeal Ureaplasma colonization and in 4.6% of noncolonized infants (P < 0.03). Bronchopulmonary dysplasia developed in 40% of intubated infants with positive endotracheal Ureaplasma cultures and only in 9.8% of infants with negative endotracheal cultures (P < 0.04). Thus Ureaplasma colonization of either the nasopharynx or the trachea was associated with an increased risk for the development of bronchopulmonary dysplasia (relative risk, 4.0 and 4.1, respectively). PMID- 1408485 TI - Lack of predictive value of maternal human immunodeficiency virus p24 antigen for transmission of infection to their children. AB - The association of maternal-to-infant transmission of human immunodeficiency virus type 1 (HIV-1) with maternal p24 antigenemia was assessed in 86 HIV-1 infected mothers. We retrospectively examined serum or plasma samples collected in the peripartum period (delivery +/- 11 days; sd 16.89 days; range, delivery +/ 2 months). Immune complexes of p24 antigen and anti-p24 antibody were dissociated using acid hydrolysis (Method A, glycine-HCl buffer; Method B, HCl) in an attempt to increase the sensitivity of the test. The detection of HIV-1 p24 antigenemia in serum was increased from 23 of 86 (26.7%) to 37 of 82 (45.1%) following acid hydrolysis with Method A (chi square = 5.4, P = 0.02) and to 36 of 78 (46.1%) with Method B (chi square = 5.874, P = 0.015). Mothers of HIV-1 infected children were no more likely to have p24 antigenemia than mothers of seroreverted infants when untreated samples were assayed (7 of 23 vs. 10 of 48; chi square = 0.348, P = 0.55). Although acid hydrolysis increased the ability to detect p24 antigen, it did not enhance any association between p24 antigenemia and maternal-to-infant transmission of HIV infection: Method A, 9 of 23 in mothers of infected children vs. 21 of 45 in mothers of seroreverted children (chi square = 0.112, P = 0.738); and Method B, 9 of 22 in mothers of infected children vs. 18 of 42 in mothers of seroreverted children (chi square = 0.014; P = 0.907), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408486 TI - IgG1, IgG2 and IgM responses to two Haemophilus influenzae type b conjugate vaccines in young infants. AB - PRP-meningococcal outer membrane protein complex (PRP-OMPC) and oligosaccharide linked to variant diphtheria toxin (HbOC) Haemophilus influenzae type b (HIB) conjugate vaccines have both been licensed for United States infants at 2 months of age. Differences in serologic responses for these vaccines have been noted with PRP-OMPC producing an early response at 2 months of age and HbOC producing a higher response after a third dose at 6 months of age. To further characterize the nature of these distinct responses, we measured the IgG1, IgG2 and IgM anti HIB concentrations by enzyme-linked immunosorbent assay after administration of both vaccines. PRP-OMPC produced an IgM and IgG1 anti-HIB response following the initial dose at 2 months of age. After two doses of HbOC an increase in IgG1 and IgM were noted and after a third dose at 6 months of age an IgG2 anti-HIB response occurred. In addition 33 study subjects were boosted with PRP-OMPC at age 18 months and compared with 34 subjects who received only a primary dose. The anti-HIB IgG1 and IgG2 concentrations following the booster dose were both significantly higher for the primed group (P = 0.0001 and P = 0.001, respectively). Both HIB conjugate vaccines produce predominantly IgG1 anti-HIB antibody responses. The early response to PRP-OMPC vaccine at 2 months of age may result from adjuvant characteristics of the OMPC. PMID- 1408487 TI - Outbreaks of summer rotavirus linked to laboratory practices. The National Rotavirus Surveillance System. AB - In temperate regions rotavirus diarrhea is a disease of the cooler months of the year, but little is known about its patterns in the summer. We report on the first year of national surveillance of rotavirus, during which we actively investigated patterns of summer activity. We obtained data on rotavirus testing from 85 laboratories in 48 states, conducted a survey of their testing practices and retested for confirmation positive specimens from laboratories reporting high rates of positivity during the summer. During 1989 participating laboratories reported 4011 specimens tested for rotavirus during July and August, of which 436 (11%) were said to be positive. Most laboratories reported low rates of positivity during these months (median percent positive, 3), but five had very high rates of summer positivity (> 30%). These five laboratories were geographically separated, and neighboring laboratories showed little rotavirus activity. Positive specimens submitted by four of these centers with high rates of summer rotavirus could not be confirmed. A survey of laboratory methods found one commercial assay (TestPack) and two laboratory practices (failure to use controls and involvement of more than six technicians in the testing process) to be associated with high rates of summer positivity. Moderate rates of positivity (11 to 30%) were fond frequently in the southwest during July and August; reference testing of specimens from these laboratories confirmed positivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408489 TI - Nontuberculous mycobacterial infections. PMID- 1408488 TI - Prevention of hepatitis B virus infection in the United States: a pediatric perspective. PMID- 1408490 TI - Candida lusitaniae infection in the newborn: case report and review of the literature. PMID- 1408491 TI - Serratia marcescens meningitis in neonates. PMID- 1408492 TI - Treatment of Bacillus Calmette-Guerin-associated lymphadenitis. PMID- 1408493 TI - Shigellosis-associated encephalopathy. PMID- 1408494 TI - Shigella and gonococcal vulvovaginitis in prepubertal central African girls. PMID- 1408495 TI - Transient seroreversion in children born to human immunodeficiency virus 1 infected mothers. PMID- 1408496 TI - Cerebrospinal fluid inflammation induced by intravenous immunoglobulins. PMID- 1408497 TI - Fluconazole pharmacokinetics in the cerebrospinal fluid of a child with Candida tropicalis meningitis. PMID- 1408498 TI - Defining delayed immunizations. PMID- 1408499 TI - Prevention of recurrent otitis media. PMID- 1408500 TI - The decline of Haemophilus disease. PMID- 1408501 TI - What constitutes a "significant" chicken-pox exposure? PMID- 1408502 TI - Mechanical ventilation in preterm infants: neurosonographic and developmental studies. AB - Surviving preterm infants of less than 34 weeks' gestation who were selected on the basis of serial cranial ultrasonographic findings during their nursery course had repeated neurologic and developmental examinations during late infancy and early childhood that established the presence (n = 46) or absence (n = 205) of spastic forms of cerebral palsy. Of the 205 infants without cerebral palsy, 22 scored abnormally low on standardized developmental testing during early childhood. The need for mechanical ventilation beginning on the first day of life (n = 92) was significantly related to gestational age, birth weight, Apgar scores, patent ductus arteriosus, grade III/IV intracranial hemorrhage, large periventricular cysts, and the development of cerebral palsy. In the 192 mechanically ventilated infants, vaginal bleeding during the third trimester, low Apgar scores, and maximally low PCO2 values during the first 3 days of life were significantly related to large periventricular cysts (n = 41) and cerebral palsy (n = 43), but not to developmental delay in the absence of cerebral palsy (n = 18). The severity of intracranial hemorrhage in mechanically ventilated infants was significantly associated with gestational age and maximally low measurements of PCO2 and pH, but not with Apgar scores or maximally low measurements of PO2. Logistic regression analyses controlling for possible confounding variables disclosed that PCO2 values of less than 17 mm Hg during the first 3 days of life in mechanically ventilated infants were associated with a significantly increased risk of moderate to severe periventricular echodensity, large periventricular cysts, grade III/IV intracranial hemorrhage, and cerebral palsy. Neurosonographic abnormalities were highly predictive of cerebral palsy independent of PCO2 measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408503 TI - Lyme arthritis as the incorrect diagnosis in pediatric and adolescent fibromyalgia. AB - In areas endemic for Lyme disease there is increasing concern and anxiety about possible chronic and untreatable manifestations of the disease. The authors have diagnosed fibromyalgia in many patients with chronic musculoskeletal complaints in whom chronic Lyme arthritis had previously been diagnosed as the cause of their joint pains. Fibromyalgia is a common disorder, causing arthralgia (not true arthritis), fatigue, and debility. The repeated and/or long-term antibiotic therapy prescribed for "chronic Lyme disease" is not successful in curing the symptoms of fibromyalgia. Especially in areas where anxiety about Lyme disease is great, it is important to be careful in diagnosing chronic Lyme disease. Fibromyalgia is a potentially treatable and curable cause of chronic complaints and should be considered in the differential diagnosis of "refractory Lyme arthritis." PMID- 1408504 TI - Prolonged dexamethasone therapy reduces the incidence of cryotherapy for retinopathy of prematurity in infants of less than 1 kilogram birth weight with bronchopulmonary dysplasia. AB - To determine whether prolonged dexamethasone therapy, used in the treatment of bronchopulmonary dysplasia (BPD), affects the incidence of cryotherapy for retinopathy of prematurity, the authors conducted a retrospective review of all infants admitted to a neonatal intensive care unit between October 1988 and October 1990 (n = 957) whose birth weights were less than 1 kg (n = 90). All admissions were reviewed to determine birth weight, gestational age, survival, incidence of BPD and cryotherapy, use and duration of dexamethasone therapy, length of mechanical ventilation, continuous positive airway pressure, and additional supplemental oxygen. Of all neonatal intensive care unit admissions, 9.4% weighed less than 1 kg, and 64% survived for greater than 28 days (n = 58). Of the survivors, 82% had BPD. Cryotherapy for retinopathy of prematurity was used only in those with birth weights of less than 1 kg and with BPD. All those treated with dexamethasone (n = 23) had BPD and significantly lower gestational ages (25.6 vs 26.4 weeks) (P = .05) and birth weights (759 vs 824 g) (P < .05) than those not treated (n = 25). Dexamethasone was used in 23 of 48 infants (9 for < or = 24 days, 14 for > 24 days). Eleven required cryotherapy: 5 of 25 with no dexamethasone, 5 of 9 treated for 24 days or less, and 1 of 14 treated for longer than 24 days (P < .04). In those treated with prolonged (> 24 days) dexamethasone, cryotherapy was significantly reduced compared with those treated for shorter periods. Although the probability was significant, the 95% confidence intervals were wide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408505 TI - Severe retinopathy of prematurity and steroid exposure. AB - During a 3-year period (1988 through 1990) an increase was observed in the number of infants born at 23- to 26-weeks' gestation who required cryotherapy for severe retinopathy of prematurity (0/20, 1988; 3/14, 1989; 6/18, 1990; P = .015). Inasmuch as this was not related to improved survival, a retrospective case control study was conducted to try to explain this observation. Of 52 surviving infants who had been born at 23 to 26 weeks' gestation, 9 required cryotherapy and the other 43 served as control subjects. There were no differences between groups in birthweight, gestational age, or the number of infants with hyaline membrane disease, intraventricular hemorrhage, or hydrocephalus. Factors related to the need for cryotherapy included patent ductus arteriosus (P = .046), mechanical ventilation for more than 21 days (P = .045), and the use of steroids for lung disease (P < .001). In this neonatal intensive care unit, steroids are administered according to the attending neonatologist's preference. Inasmuch as steroids are considered only for infants still ventilator dependent at 21 days, this group was analyzed separately (n = 36). Of the 21 factors examined, only the use of steroids for lung disease was associated with the need for cryotherapy (P < .001). PMID- 1408506 TI - Oral ketamine premedication to alleviate the distress of invasive procedures in pediatric oncology patients. AB - This study prospectively evaluated the efficacy of oral ketamine in alleviating procedure-related distress in pediatric oncology patients. Ketamine (10 mg/kg) was administered orally to 35 children and adolescents, ranging in age from 14 months to 17 years (mean = 6.5 years). Procedure-related distress was evaluated by using parent/clinician ratings and the Observational Scale of Behavioral Distress (OSBD-R). Eighty-seven percent of children were sedated within 45 minutes. Clinician and parent ratings were similar, with 77% rating procedural distress as low (0 to 3). The OSBD-R scores were low throughout all phases of the study. Although this study was neither randomized nor placebo-controlled, statistical comparison of the OSBD-R scores of the patients who received oral ketamine with those of historical controls (from a study previously performed at the same institution but using intravenous midazolam) showed significantly less distress (P < .001) during the procedure in children who received oral ketamine. Additionally, OSBD-R scores of the patients who received oral ketamine were significantly lower (P < .001) during all phases than those of the saline placebo group in the other study. No cardiorespiratory side effects related to ketamine were noted. The majority of patients showed recovery from sedation within 2 hours following the procedure. In conclusion, oral ketamine effectively alleviated procedure-related distress in pediatric oncology patients. PMID- 1408507 TI - Variability and self-regulation of energy intake in young children in their everyday environment. AB - Recent data from small numbers of children studied under controlled protocols indicate that intraindividual variation in energy consumption over 24 hours is smaller than variation from eating occasion to eating occasion, implying that children self-regulate their energy consumption. This hypothesis was tested in children living in their everyday environment. Between 1986 and 1989, 24-hour recalls were administered on seven occasions (four times in 1986 through 1987 and three times in 1988 through 1989) to the mothers of 181 preschool children in New York City. Each 24-hour period was divided into six meals or snacks. The coefficient of variation (standard deviation divided by the mean) was calculated for each child for energy consumption at each eating occasion and for the day as a whole. Coefficients of variation for energy consumption at the six eating occasions ranged from 46.5% to 165.8%, compared with 30.3% for the whole day. This coefficient of variation for the observed whole-day energy consumption was significantly less (P < .001) than would be expected if no autoregulation of energy intake (no meal-to-meal correlation) occurred. These findings in children living in their everyday environment are consistent with observations under more controlled study conditions. These data suggest that children who eat less at one meal compensate at another, although the data do not address the issues of longer term energy self-regulation, overall energy balance, or diet quality. PMID- 1408508 TI - Dietary intake of healthy children with cystic fibrosis compared with normal control children. AB - Because a low calorie intake may result in growth failure and malnutrition in patients with cystic fibrosis (CF), the dietary and energy intakes of 22 children with CF who had mild lung disease and excellent Shwachman scores were examined and compared with those of 23 normal control subjects similar in age (5 to 10 years), gender, and weight. The children with CF consumed significantly more calories than the control subjects. Calorie intake was 111 +/- 19.9% (mean +/- SD) of estimated requirements (World Health Organization recommendations) for the CF group and 97 +/- 18.7% for the control group (P = .014). Calories consumed per kilogram of body weight were 117% of World Health Organization (CF) vs 97% (control) (P = .009). Calorie intake compared to the 1989 Recommended Dietary Allowance was 106 +/- 20.6% for the CF group vs 93 +/- 19.1% for the control group. Fat consumed as a percent of total calories was similar: 33.5% (CF) vs 32.2% (control). All children with CF had pancreatic insufficiency and, on average, consumed a large number of pancreatic enzyme supplements, resulting in dietary fat absorption of 86 +/- 12%. It is concluded that these children with CF were able to maintain normal growth and energy stores on a diet that was relatively high in calories compared to control subjects and moderate in percent fat, along with an aggressive pancreatic enzyme supplement regimen. PMID- 1408509 TI - Sleeping through the night: a developmental perspective. AB - This study examines falling asleep and night waking in human infants during the first 8 months of life. All-night time-lapse video recordings were obtained at 3 weeks and 3 months of age; a Sleep Habits Interview was completed at these ages and repeated at 8 months of age by telephone interview. At the 3-week and 3-month ages, self-report measures of maternal psychologic distress, depression, and self esteem were also obtained. The data are examined from both cross-sectional (age group) and longitudinal (individual) perspectives. Parent-infant interactions at bedtime and during the middle of the night changed significantly with increasing age. At 3 weeks of age, most infants were put into their cribs for the night already asleep. When they awakened in the middle of the night, they were removed from their cribs. By the time they returned to their cribs, they were again asleep. By 3 months of age, infants who were put into the crib awake at bedtime and allowed to fall asleep on their own were more likely to return to sleep on their own after awakenings later in the night. In contrast, infants who were put into the crib already asleep at the beginning of the night were significantly more likely to be removed from the crib following a subsequent nighttime awakening. Thus, the pattern of bedtime sleep onset was related to sleep onset following an awakening in the middle of the night. This association was present at 8 months as well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408510 TI - Neonatal therapeutic intervention scoring system: a therapy-based severity-of illness index. AB - Severity-of-illness scales have proven valuable in assessing clinical outcomes and resource consumption in adult and pediatric intensive care, but they have been less extensively developed for neonatal care. The National Therapeutic Intervention Scoring System (NTISS) was created by modifying the Therapeutic Intervention Scoring System (TISS). From the 76 original TISS items, 42 were deleted and 28 added to form the NTISS. Like TISS, NTISS assigns score points from 1 to 4 for various intensive care therapies. Admission-day NTISS scores were calculated for 1643 newborns admitted to three neonatal intensive care units (NICUs) between November 1, 1989, and September 30, 1990. NTISS scores ranged from 0 to 47 with a mean of 12.3 +/- 8.7 (SD). There was little correlation with birth weight (r = -.11) or gestational age (r = -.17), but NTISS scores were highly correlated with expected markers of illness severity, including mortality risk estimates by neonatal attending physicians (r = .70, P < .0001), in-hospital mortality rates (P < .05), and a measure of nursing acuity (Medicus) (r = .69, P < .0001). In addition, admission-day NTISS scores were found to be predictive of both NICU length of stay (r = .37, P < .0001) and total hospital charges for survivors (r = .65, P < .0001). It is concluded that NTISS is a valid measure of therapeutic intensity that is independent of birth weight and can be used as an indicator of neonatal illness severity and resource utilization. Further validation in other NICUs is required. PMID- 1408511 TI - Evaluation of the reconstructed carotid artery following extracorporeal membrane oxygenation. AB - Over a 12-month period, 28 neonatal patients in respiratory failure were supported with extracorporeal membrane oxygenation (ECMO), and 11 of these underwent successful repair of the right carotid artery post-ECMO. Nine of 11 were studied with duplex color-flow Doppler imaging between 14 and 109 days of age and again at 1 year of age. A velocity ratio (A/B) of the peak systolic velocity above the level of the anastomosis to the peak systolic velocity below the anastomosis was measured to assess the degree of stenosis, if any, at the repair site. Antegrade flow through the carotid was detected post-ECMO in 8 of 9 infants, and antegrade and retrograde flow was documented in 1 infant. A/B ratios ranged from 1.00 to 8.60 (A/B ratio of 1 is normal; 2.0 indicates at least a 50% obstruction to flow). Four of 9 patients had ratios greater than 2.0, and 8 of 9 exhibited some evidence of obstruction. Follow-up scans were performed on 8 of 9 infants between 12 and 18 months of age. All infants examined showed marked improvement in A/B ratio and patency of the vessel, documenting that initial narrowing of the vessel is reversible. No infant had evidence of embolic phenomena to the right side of the brain by magnetic resonance imaging. Repair of the common carotid artery post-ECMO is technically feasible without increasing the risk of brain injury. PMID- 1408512 TI - Subspecialization within pediatric practice: a broader spectrum. AB - This study was undertaken to describe subspecialty characteristics and practices of the population of pediatricians given the ongoing controversy regarding a projected manpower oversupply of general pediatricians. A questionnaire was mailed to a national random sample of 1620 United States physicians listed in the American Medical Association's Physician Masterfile as being in office-based pediatric practice. The final response rate was 63%. Seventy percent of respondents designated their practices as "general pediatrics" versus 17% as "general pediatrics with a specific subspecialty interest" and 13% as "subspecialty practice." The general pediatricians with a specific subspecialty interest were intermediate in the proportion that had some training in a pediatric fellowship program (general pediatricians with a specific subspecialty interest, 63% versus general pediatricians, 14%, P < .0001, and pediatricians with a subspecialty practice, 92%, P < .0001) and that were certified in a pediatric subspecialty by the American Board of Pediatrics (general pediatricians with a specific subspecialty interest 16% versus general pediatricians, 2%, P < .0001, and pediatricians with a subspecialty practice, 62%, P < .0001). They were also intermediate in the proportion involved in various academic pursuits. Their practices, however, more closely resembled general pediatricians than pediatricians with a subspecialty practice in their location, setting, associates, and commitment to primary care. They were more likely than general pediatricians to utilize or provide specialized tests or procedures. A large percentage of pediatricians incorporate subspecialty elements into their general pediatric practices. Models of current and projected pediatric manpower supply need to be reassessed in light of this form of practice. PMID- 1408513 TI - Day care center attendance and diarrheal morbidity in Colombia. AB - This study was designed to determine whether day care center attendance was associated with increased risk of diarrheal disease among poor children in an urban, developing country setting. From July 17 to December 18, 1988, mothers of 493 Colombian children less than 5 years old (241 attendees and 252 nonattendees) were interviewed weekly about diarrheal events during the previous week. The incidence of diarrhea was greater for day care center attendees than for nonattendees (3.2 vs 2.0 episodes per child-year, P < .0005). For children less than 2 years of age, attendees experienced 7.2 episodes/child-year vs 3.5 episodes per child-year for nonattendees (P < .0005). Analyses controlling for water source and availability, excreta disposal, socioeconomic status, and duration of follow-up showed that the increased diarrheal risk was limited to children younger than 3 years of age spending more than 30 hours per week in the centers. In addition, although the risk among attendees of suffering diarrheal episodes of longer duration was fairly constant across levels of socioeconomic status, this risk was inversely proportional to socioeconomic status for nonattendees. In summary, the increase in risk of diarrhea among young, full-time day care attendees was modest, yet important, because diarrhea continues to be a major cause of morbidity and mortality in Colombian children. PMID- 1408514 TI - Health insurance coverage of adolescents: a current profile and assessment of trends. AB - Data from the National Health Interview Survey reveal that 4.7 million or 15% of US adolescents aged 10 through 18 were uninsured in 1989. Among adolescents, 73% were privately insured, 10% were publicly insured, and 2% were both privately and publicly insured. Poor, near-poor, and minority adolescents were at the greatest risk for lack of health insurance coverage. Among adolescents without insurance, cost continued to be cited as the leading barrier to obtaining coverage. A comparison of 1989 National Health Interview Survey data with a previous analysis, in which 1984 data were used, revealed a 10% increase in the proportion of adolescents without insurance coverage. The increase in the proportion of uninsured adolescents was entirely attributable to an erosion of private health insurance coverage. No significant change occurred in the proportion of adolescents with coverage under public programs. Planned expansions of the federally and state-financed Medicaid programs will help to stem further increases in the size of the uninsured adolescent population. However, unless marked improvements occur in the private health insurance sector, progress will be limited. PMID- 1408515 TI - The cost of assistive devices for children with mobility limitation. AB - This study evaluated the costs of assistive devices for children with motor limitations at home, in day care, and in school, and the effect of diagnosis and severity of disabilities on costs. 201 children (mean age 7.4 years) who used 1274 various assistive devices (85.7% at home, 6.1% in day care, and 8.2% in school) were studied. The cost per device varied from $8.14 to $8138 with an average value of $539 per device. The distribution of costs per capita was unequal: 52.2% of children used 15.6% of total costs and 4.5% of children used 20.8% of total costs. The severity of motor impairment and the age of the child were the most important indicators associated with the need and cost of assistive devices. Assistive devices for basic needs, such as sitting, mobility, and personal hygiene, had a relatively low effect on costs in comparison with the high-technology devices, like powered wheelchairs and computers. Better cooperation with day care and school professionals, better assessment of needs, follow-up and recirculation of assistive devices are ways to promote rehabilitation services and partly solve the discrepancies between the costs of available technology and the resources to pay for it. PMID- 1408516 TI - Biologic, foster, and adoptive parents: care givers of children exposed perinatally to human immunodeficiency virus in the United States. The Pediatric Spectrum of Disease Clinical Consortium. AB - Children born to human immunodeficiency virus (HIV)-infected mothers often do not live with a biologic parent because of drug use, illness, or death of the mother. Public health officials need to know the number and proportion of children who will require care by someone other than a biologic parent (alternative care giver). The Pediatric Spectrum of Disease project, conducted in six different geographic regions in the United States, assesses issues specific to HIV in children. Among the information being collected in this study are data regarding the primary care giver. Of 1683 children born to HIV-infected mothers and enrolled through 1990, 55% (937) were living with a biologic parent, 10% (169) with another relative, 28% (455) were in foster care, 3% (55) had been adopted, and 4% (67) lived in group settings or with other care givers. In all locations and for all racial/ethnic groups, children of mothers who used intravenous drugs were more likely to be living with an alternative care giver than were children of mothers who had not used intravenous drugs (odds ratio 4.15). However, there were striking variations by study location (odds ratio range 1.4 to 7.2). The data suggest that maternal drug use may be the most important factor determining whether a child lives with a biologic parent and that there are also regional differences in alternative care placement. PMID- 1408517 TI - Contribution of the 13C-urea breath test to the detection of Helicobacter pylori gastritis in children. AB - Serology, 13C-urea breath test, histology, Campylobacter-like organism testing, and culture were performed in 95 consecutive children to evaluate the contribution of these tests to the detection of Helicobacter pylori infection. In analyses considering any combination of three positive tests as "gold standard" for diagnosing H pylori infection, 26 children were Helicobacter positive (27%), which is only one patient more than the number of children with only a positive culture. The accuracy of culture was excellent when "any combination of three positive tests" was used as the gold standard (sensitivity 96%, specificity 100%, positive predictive value 100% [false positivity 0%], negative predictive value 99% [false-negative results 1%]). The results of invasive and noninvasive tests were comparable. When culture was considered as "gold standard," the sensitivity of serology and 13C-urea breath test was 96%; the specificity was 96% and 93%, respectively; the positive predictive value was 89% and 83% (false-positive results in 11% and 17%); and the negative predictive value for both was 99% (false-negative results in 1%). It is concluded that culture can be used as gold standard, but that non-invasive tests such as serology and/or 13C-urea breath test can be used to diagnose H pylori infection in children, since each has at least 95% sensitivity and 92% specificity. PMID- 1408518 TI - The sit-up test: an alternate clinical test for evaluating pediatric torticollis. AB - The sit-up test, a new evaluation method for differentiating between ocular and orthopaedic torticollis, was evaluated against the monocular occlusion test, using results of three-step testing for standardization. The study group consisted of 31 patients with torticollis between the ages of 4 and 12.5 years. Subjects were selected based only on their ability to cooperate with three-step testing. Three-step testing identified 27 of the 31 patients as having ocular torticollis, with the remaining 4 having an orthopaedic etiology. Sit-up testing correctly identified all 27 ocular torticollis patients, with no false positives or false negatives. Monocular occlusion testing detected at best 22 (81.4%) of the ocular torticollis patients, with no false positives. PMID- 1408519 TI - Risk factors for the central nervous system manifestations of gastroenteritis associated hemolytic-uremic syndrome. AB - Hemolytic-uremic syndrome is usually a consequence of enteric verotoxigenic Escherichia coli infection, and a prevailing hypothesis contends that systemically absorbed verotoxins are responsible for the multiple organ involvement. In an attempt to determine whether the central nervous system (CNS) manifestations could occur owing to factors that reflect a toxin insult, the authors studied the association of clinical and laboratory variables with the development of neurological disease. Ninety-one patients with hemolytic-uremic syndrome from 1982 through 1990 were included. Twenty-seven (18 female, 9 male) had a CNS disorder; 17 of these had seizures and there were two deaths. Multivariate analyses led to the following observations: female gender (odds ratio [OR] 8.50; 95% confidence interval [CI] 2.08 to 50.0), prolonged use of an antimotility pharmacological agent (OR 8.50; 95% CI 1.69 to 42.81), and an increased hemoglobin level (OR 1.11; 95% CI 1.05 to 1.17) were associated with an increased risk for developing a neurological manifestation. Prior administration of a blood product was associated with a decreased risk (OR 0.12; 95% CI 0.02 to 0.52). The findings suggest that other mechanisms for CNS disease may exist in addition to direct toxin insult. PMID- 1408521 TI - Acute pancreatitis in a 12-year-old girl after an erythromycin overdose. PMID- 1408520 TI - Near fatal fire ant envenomation of a newborn. PMID- 1408522 TI - Cerebral infarction complicating hemorrhagic shock and encephalopathy syndrome. PMID- 1408523 TI - Eosinophilia-myalgia syndrome in a child with phenylketonuria. PMID- 1408524 TI - Patterned abusive bruises of the buttocks and the pinnae. PMID- 1408526 TI - American Academy of Pediatrics Committee on Pediatric Emergency Medicine: Access to emergency medical care. PMID- 1408525 TI - Steroids, chronic lung disease, and retinopathy of prematurity. PMID- 1408527 TI - Temperature measurement--gold standard. PMID- 1408528 TI - Temperature measurement. PMID- 1408529 TI - Carnation marketing practices. PMID- 1408530 TI - Behavior management of pediatric dental patients. American Academy of Pediatrics Committee on Child Abuse and Neglect. PMID- 1408531 TI - Naftifine (Naftin) in pediatrics. PMID- 1408532 TI - Lupus nephritis study--questions. PMID- 1408533 TI - Diaper debate continues. PMID- 1408534 TI - Impact of childhood asthma on health. AB - In 1988, the National Health Interview Survey contained a supplemental questionnaire on childhood conditions that included asthma. The authors used these data from 17,110 households to determine the disease burden resulting from asthma and to determine the functional status of children with and without asthma by linking information from the core and supplemental questionnaires. The prevalence of asthma in children younger than 18 years of age in the United States as reported by an adult in the household was 4.3% in 1988 and was 3.2% in 1981, the last time a comparable questionnaire was used in the National Health Interview Survey. The difference between the prevalences of asthma was statistically significant (95% confidence interval for the difference was 0.7% to 1.5%). An estimated 2.7 million children younger than 18 years were reported by an adult in the household to have had asthma in the past year. The added burden of illness experienced by children with asthma compared with children without asthma was an additional 10.1 million days missed from school, 12.9 million contacts with medical doctors, and 200,000 hospitalizations. Almost 30% of children with asthma had some limitation in activity, compared with only 5% of children without asthma. A greater proportion of black children experienced more severe functional disability and had more frequent hospitalizations than white children with asthma. Ten percent of children with asthma had severe disease as measured by frequency of bother and limitations in function; these children accounted for 35% of hospitalizations for asthma and 77% of the days in the hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408535 TI - Improved survival accounts for most, but not all, of the increase in bronchopulmonary dysplasia. AB - The incidence of bronchopulmonary dysplasia (BPD) increased from 10.6% in 1976 through 1980, to 21.7% (1981 through 1985), and to 32.9% (1986 through 1990) in very low birth weight neonates (1500 g or less) admitted to the Vanderbilt Neonatal Intensive Care Unit, while there was a concurrent decline in incidence of neonatal death (NEOD) during the same periods (26.4%, 18.3%, and 15.9%, respectively). Population changes in risk factors (birth weight, sex, race, location of birth, gestational age, diagnosis of hyaline membrane disease, and 5 minute Apgar score) over time do not account for this increase. To estimate the proportion of the increase in BPD attributable to the concurrent decline in NEOD during these periods, separate logistic regression models for NEOD and BPD were calculated from patients born during 1976 through 1985. These results were used to predict the expected number of cases of NEOD and BPD during 1986 through 1990, assuming that the adjusted incidence of NEOD and BPD remained constant from 1976 through 1985, to 1986 through 1990. The increase in the combined outcome, NEOD/BPD, over the three time periods (34.2%, 36.1%, and 43.5%) remained statistically significant after adjustment for the risk factors listed above. During 1986 through 1990, the predicted number of NEOD was 83 more than the number observed, while the predicted number with BPD was 115 less than the number observed. If all 83 averted cases of NEOD during 1986 through 1990 had developed BPD, then 83 (72%) of the 115 excess cases of BPD could be attributed to averted NEOD. The approximate 95% confidence interval for this estimate was 58% to 87%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408536 TI - Birth asphyxia alters neonatal intestinal motility in term neonates. AB - As an extension of an earlier study showing that manometry can identify preterm newborns at risk for feeding intolerance, the authors investigated whether abnormalities of intestinal motor activity underlie the feeding intolerance seen in asphyxiated newborns. Low-compliance perfusion manometry was recorded within the first postnatal week in 25 term neonates admitted consecutively for respiratory diseases. Eleven of these neonates were identified to have experienced birth asphyxia because three concurrent features were present: 1 minute Apgar score of less than 2; 5-minute Apgar score of less than 4; and recurrent seizures within the first 48 postnatal hours. The remaining 14 neonates, who did not have any of these three characteristics, were considered to be nonasphyxiated control neonates. Motor activity differed in nonasphyxiated and asphyxiated neonates during fasting and feeding. During fasting, asphyxiated neonates had less migrating activity than nonasphyxiated neonates. In addition, episodes of motor quiescence and clustered phasic activity were less well organized in asphyxiated neonates. Both groups of neonates displayed a change in motor activity in response to a feeding infusion; however, the response was initiated significantly sooner in asphyxiated than in control neonates. All of the 11 asphyxiated neonates were intolerant of enteral feedings during the first poststudy week, but no control neonate was feeding intolerant. Six of the asphyxiated neonates were reevaluated 1 to 2 weeks later. During this latter study, motor activity in these asphyxiated neonates was similar to that of nonasphyxiated neonates; 5 of 6 of these neonates subsequently tolerated enteral feedings. It is speculated that changes in motor activity underlie the feeding intolerance that asphyxiated neonates typically exhibit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408537 TI - Double versus single phototherapy in low birth weight newborns. AB - Conventional phototherapy systems that simultaneously irradiate the front and the back of the baby lower the serum bilirubin level more rapidly than one-sided systems, but they are impractical. Fiberoptic phototherapy makes it easy to administer conventional phototherapy from above while the infant lies on a fiberoptic phototherapy blanket. Newborns with birth weights less than 2500 g were randomly assigned to receive either single (n = 37) or double (n = 33) phototherapy. The groups were similar in clinical and laboratory characteristics. After 18 hours of therapy the serum bilirubin concentration declined by 31 +/- 11% in the double and 16 +/- 15% in the single phototherapy group (2.9 +/- 1.1 vs 1.6 +/- 1.4 mg/dL), and the difference in the total serum bilirubin levels after 18 hours of therapy was significant (double phototherapy group 7.1 +/- 2.7 mg/dL vs single phototherapy group 8.2 +/- 2.6 mg/dL). After 18 hours of treatment the serum bilirubin level was less than the phototherapy threshold level in 26 of 37 single phototherapy patients vs 32 of 33 double phototherapy patients. Double phototherapy was well tolerated. It is concluded that this type of double phototherapy is more effective than single phototherapy in low birth weight newborns. Double phototherapy may be useful when it is necessary to reduce an elevated serum bilirubin level as rapidly as possible or when the bilirubin level is rising with single phototherapy. PMID- 1408538 TI - Recombinant erythropoietin as treatment for the late hyporegenerative anemia of Rh hemolytic disease. AB - Infants with Rh hemolytic disease can develop a "late" anemia characterized by low serum concentrations of erythropoietin but erythroid progenitors that remain highly erythropoietin-responsive. Erythropoietin administration was evaluated in two patients as an alternative to transfusion. Reticulocyte counts increased after 5 days of treatment, and hematocrits increased after 10 days. Neither patient received erythrocyte transfusions following erythropoietin therapy. PMID- 1408539 TI - Impact of a matched term control group on interpretation of developmental performance in preterm infants. AB - One hundred twenty-four children who were born at 24 to 31 weeks' gestation and 124 term children matched in social background underwent serial developmental evaluations. The Bayley Mental Developmental Index at 6, 15, and 24 months and the McCarthy General Cognitive Index at 4 years were used to classify cognitive outcome for preterm children as normal (indices higher than 1 SD below the mean), mild-moderately delayed (indices between 1 and 2 SD below the mean), or severely delayed (indices > or = 2 SD below the mean). Classifications based on norms derived from the performance of the term control group were compared with those based on published standardized test scores. The control group had substantially higher mean (+/- SD) Bayley Mental Developmental Indices at 6 (111 +/- 11), 15 (114 +/- 13), and 24 months (115 +/- 21) than the published test mean (100 +/- 16). Consequently, significantly more preterm children were classified as normal when the Bayley test mean was used than when the performance of the control group was used to define the normal range (84% vs 52% at 6 months, 82% vs 49% at 15 months, and 70% vs 47% at 24 months). Severe cognitive delays were infrequent when defined by test mean (6% to 11%) but two to three times greater when the control group scores were used. In contrast, the control group had a mean McCarthy General Cognitive Index at 4 years (102 +/- 14) that was similar to the published test mean (100 +/- 16).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408540 TI - Delayed recognition of human immunodeficiency virus infection in preadolescent children. AB - Thirty-two (18%) of 181 children cared for at our institution who were infected with the human immunodeficiency virus type 1 (HIV-1) were first seen, and HIV was diagnosed, when they were 4 years of age and older. Initial complaints or diagnoses for these children included the following: hematologic disorders (5) (3 idiopathic thrombocytopenic purpura, 1 neutropenia, 1 anemia); recurrent bacterial infections (10); Pneumocystis carinii pneumonia (3); developmental delay (1); skin disorders (2) (1 genital wart, 1 chronic zoster); weight loss (3); malignancy (1); and nephropathy (1). Eight children were referred for evaluation because of maternal HIV-1 infection. The risk factors for HIV-1 infection included maternal/perinatal exposure (22), perinatal blood transfusion (6), blood transfusion during infancy (2), and sexual abuse (2). Ten (31%) of the 32 children have subsequently died. The longest survival from perinatal infection was 12 years. HIV-1 infection in children can result in a prolonged clinical latency and can masquerade as other pathologic conditions. The absence of clinical symptoms in older children at risk for HIV-1 infection should not deter HIV testing. PMID- 1408542 TI - Hyperactivity in school-age boys and subsequent risk of injury. AB - Hyperactive boys between 6 and 8 years of age, identified through systematic population-based screening of a community in London, were compared prospectively with a nonhyperactive control group to determine whether they were at greater risk of sustaining injuries. The study sample was drawn from 1296 completed parent and teacher questionnaires. Hyperactive groups were designated in three ways (parental report, teacher report, and combined parent and teacher report). Injuries were assessed by reviewing the medical records of the five emergency departments serving the community. Although boys with conduct problems did sustain more injuries than control subjects, no relationship between hyperactivity and injury was found. Similarly, when milder injuries were excluded from the analysis, the association remained negative. The absence of an association could not be accounted for by differential parental protectiveness of boys designated hyperactive. This study, which has a power of .80 to determine an increase in the relative risk of injury of 1.5, found no effect for hyperactive behavior in boys. Hyperactive behavior is probably not a risk factor for injury; if it is, it exerts a modest effect, less than 1.5, therefore accounting for less than 4% of injuries to school-aged boys. PMID- 1408541 TI - Mental disorders in chronically ill children: parent-child discrepancy and physician identification. AB - Mental disorders affect 18% to 20% of children and adolescents. The rate in children with chronic illness is probably higher. This study of chronically ill children addresses the discrepancy between parent and child reports of child psychiatric disorders and the extent to which pediatricians agree with reports by children and parents regarding such problems. Eighty-three subjects, aged 9 to 18 (mean = 12.6), were recruited; they had the following diagnoses: cystic fibrosis, diabetes, inflammatory bowel disease, and cancer. Subjects and one parent were interviewed separately, using the Diagnostic Interview Schedule for Children (DISC-2.1). The subject's physician completed a questionnaire asking about the presence of a range of mental disorders. Forty-one (49%) subjects reached threshold criteria for a psychiatric diagnosis, using both parent and child as informants. Psychiatric disorders were identified in only 22 subjects (54%) by the child and in 28 (68%) by parent alone. Thus, reliance on one informant resulted in failure to identify one third to one half of psychiatric disorders. Physicians' ratings agreed significantly with children's reports but not with parental reports, suggesting that physicians are sensitive to children's concerns but may underestimate the value and importance of parents' reports. Clinical and research evaluations of chronically ill children, as well as clinician identification of mental health problems, will be influenced by the choice of informant. PMID- 1408543 TI - Wheezing in infants with cystic fibrosis: clinical course, pulmonary function, and survival analysis. AB - Wheezing is a common finding in infants with cystic fibrosis (CF). This study was undertaken to determine the prevalence of wheezing in infants with CF and to compare the clinical outcome of those who wheezed in infancy with that of those who did not. The study cohort included 229 CF patients born between 1965 and 1979 with CF diagnosed before 2 years of age. Fifty-seven (25%) had physician documented wheezing during the first 2 years of life. Wheezing had resolved by the age of 2 years in 50% of the patients and by the age of 4 years in 75%. Although wheezing seemed to be linked to a family history of allergy and asthma, the frequency of the delta F508 mutation was similar to that of the non-wheezers. There was no significant difference in survival at the age of 13 years between the two groups. At the age of 7 years, patients who had wheezed had significantly lower forced expiratory flow rate at mid-expiratory phase (85 +/- 34% predicted) compared with those with no wheezing history (101 +/- 34% predicted). At the age of 13 years, forced expiratory volume in 1 second values was lower in the wheezing group (69 +/- 24% predicted vs 78 +/- 21% predicted), as was forced expiratory flow rate at mid-expiratory phase (56 +/- 33% predicted vs 69 +/- 30% predicted). In conclusion, although wheezing in infants with CF seems to have diminished with age, pulmonary function abnormalities were more evident at 7 and 13 years of age in the group that wheezed than in the group that did not. PMID- 1408544 TI - Kernicterus in preterm newborns: past, present, and future. AB - This historical overview of kernicterus in prematurity, from the 1950s to the present, provides a unique perspective on this clinical conundrum. Three separate periods of pediatric history are detailed in relationship to our understanding of kernicterus in the preterm newborn: (1) the pre-intensive care era (1950 to 1965); (2) the low bilirubin kernicterus era (1965 to 1982); and (3) the 1980s. Each period demonstrates selected insights regarding kernicterus in prematurity, and together with recent reports suggest that premature newborns are now at extremely low risk of developing kernicterus when managed using current standards of care. However, the current conservative empiric guidelines for preventing kernicterus are questioned, and it is suggested that additional study is needed to clarify this issue in the 1990s. PMID- 1408545 TI - Ethical decisions in neonatal intensive care units: the Dutch experience. PMID- 1408546 TI - Short-term effects of feed composition on sleeping and crying in newborns. AB - To determine whether the composition of feedings would affect newborn behavior independently of the act of feeding itself, 53 two- to three-day-old normal newborns were randomly assigned to receive an extra feeding of water, carbohydrate (lactose), or balanced formula 3 hours after their usual early morning feeding. Previous studies in adult humans and animals, and a single study in human newborns, have indicated that more sleep might be expected following the carbohydrate feed compared with the water and balanced-formula feeds because of recruitment of centrally mediated serotonergic systems. Behavioral effects were assessed for 40 minutes postfeeding by direct observation of the newborn's states (quiet, active, and indeterminate sleep; drowsiness; non-cry wakefulness; and fret/cry). Feed composition did affect behavior, and the effects were fairly specific to particular newborn states. Non-cry wakefulness and drowsiness were unrelated to the presence or type of nutrients, but they tended to occur soon after the meal in all groups. Crying was increased in water-fed newborns relative to both carbohydrate- and formula-fed newborns. Sleeping showed specific patterns of change in all three groups. Sleep duration was increased in the balanced formula group compared with the water group throughout the observation period. Contrary to the prediction, sleeping duration in carbohydrate-fed newborns never exceeded that of formula-fed newborns; rather, it resembled that of water-fed newborns early in the postprandial period, but formula-fed newborns later. These effects could not easily be explained by potential confounding factors such as handling, volume ingested, caloric intake, or plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408547 TI - Risk of sepsis in newborns with severe hyperbilirubinemia. AB - Because bacterial infection is a potential cause of hyperbilirubinemia, some authors suggest that newborns with significant unexplained indirect hyperbilirubinemia should be evaluated for sepsis. We reviewed the charts of 306 newborns admitted to a pediatric ward within 21 days of birth with a diagnosis of indirect hyperbilirubinemia (peak serum bilirubin level 316 +/- 48, range 217 to 498 mumol/L) (18.5 +/- 2.8, 12.7 to 29.1 mg/dL). Ninety percent were fully or partially breast-fed. Sepsis was identified in 0 of 306 newborns (upper 95% confidence limit for the risk of sepsis = 1%). The overwhelming majority of newborns who require readmission to hospital for indirect hyperbilirubinemia are healthy, breast-fed newborns and do not need to be investigated for sepsis. If indirect hyperbilirubinemia is ever the only manifestation of bacteremia or incipient sepsis, it must be a rare event. PMID- 1408548 TI - Audiologic assessment of extremely low birth weight infants: a preliminary report. AB - The aim of this study was to assess all relevant aspects of auditory function, including acuity and perception, of a cohort of extremely low birth weight (< 1000 g) children who survived to 8 years of age; 42 of the 59 consecutive survivors born over a 4-year period from January 1, 1977, had a full auditory assessment. Of the 42 children, 4 (9.5%) had a sensorineural hearing impairment, 5 (11.9%) had a conductive hearing impairment, 24 (57.1%) had figure/ground differentiation problems, and 20 (47.6%) had a short-term auditory memory problem. The 4 children with sensorineural hearing impairments had had significantly higher maximum concentrations of bilirubin in the newborn period (median 167 mumol/L vs 138 mumol/L and had required more intensive care; at 8 years of age they were significantly disadvantaged in verbal ability. The 5 children with conductive hearing impairments were not significantly different on any perinatal or other 8-year outcome variables. The proportion with figure/ground differentiation problems (57.1%) was significantly higher than in a normative population (11.7%, chi 2 = 24.2). Extremely low birth weight children with figure/ground differentiation problems were more likely to be restless in the classroom (45.0% [9/20]) than those without these problems (16.7% [2/12]), but the difference was not statistically significant (chi 2 = 2.7). Children with short-term auditory memory problems had significantly higher maximum bilirubin concentrations in the newborn period (median 152 mumol/L vs 137.5 mumol/L). At 8 years of age they had significantly reduced intelligence and reading ability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408549 TI - Some remarks on teaching: three insights into the purpose and process of teaching medical students. PMID- 1408550 TI - Kernicterus in preterm infants; lest we forget (to turn on the lights) PMID- 1408551 TI - Single daily bottle use in the early weeks postpartum and breast-feeding outcomes. AB - A prospective study of breast-feeding mothers was undertaken to determine the effects of limited bottle use and infant temperament on breast-feeding outcomes. White, married, primigravida women who were committed prenatally to breast feeding for at least 6 weeks (n = 121) were randomly assigned to one of two groups: a planned bottle group that would offer one bottle daily between the second and sixth weeks postpartum and a total breast-feeding group that would avoid bottles during the same period. Group assignment had no effect on the occurrence of breast-feeding problems, on mothers' achievement of 90% of their prenatal breast-feeding duration goals, or on weeks to weaning across the study period. At 6 months postpartum, 59% of the planned bottle group and 69% of the total breast-feeding group were still breast-feeding. No main or interactive effects of infant temperament on breast-feeding outcomes were found. PMID- 1408552 TI - Total bone mineral content and body composition by x-ray densitometry in newborns. AB - Measurement of total body bone mineral content and body composition has not previously been convenient in the newborn. X-ray densitometry, otherwise known as dual-energy x-ray absorptiometry (DEXA), has been used in adults to assess with accuracy and precision the total body mineral content, lean mass, and fat. Body composition measurements were determined in vivo by DEXA in term newborns, and they were compared with values reported by chemical analysis of the cadaver, with skin-fold thickness measurements, and with bone mineral content measured by single photon absorptiometry. The intermeasurement coefficient of variation was < or = 2.5% for bone mineral content, and < or = 1% for fat and lean mass. The values for bone mineral content, fat, and lean mass fall within the ranges expected based on the reported values measured by chemical analysis of the infant cadaver. Triceps and quadriceps skin-fold measurements were best correlated with total body fat as measured by DEXA. The bone mineral content of the distal third radius site as measured by single photon absorptiometry in newborns showed significant correlation with total body bone mineral content. DEXA provides a reproducible and convenient method for the determination of body composition in newborns. PMID- 1408553 TI - Validating current immunization practice with young infants. PMID- 1408554 TI - American Academy of Pediatrics Ad Hoc Task Force on Definition of the Medical Home: The medical home. PMID- 1408555 TI - American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn: Guidelines for prevention of group B streptococcal (GBS) infection by chemoprophylaxis. PMID- 1408557 TI - Bereavement. PMID- 1408556 TI - 'Guidelines' versus the legal standard of care and screening for polycythemia. PMID- 1408558 TI - Presurgical routine screening. PMID- 1408559 TI - Treatment of theophylline poisoning. PMID- 1408560 TI - The "dose" question. PMID- 1408561 TI - European surfactant trial: questions about the protocol. PMID- 1408562 TI - Sleeping positions. PMID- 1408563 TI - Sleeping position and sudden infant death. PMID- 1408564 TI - Bronchopulmonary dysplasia criteria: a mathematical impossibility. PMID- 1408565 TI - [The role of Pneumococcus in the development of acute bronchitis in young children]. AB - To study the etiological role of Streptococcus pneumoniae in bronchial inflammation, 49 children with acute bronchitis and 21 children with acute nasopharyngitis were examined. The given patients' groups manifested no significant differences in the microflora of the upper respiratory tract, serotype landscape of pneumococcus, the level and dynamics of the immunologic characteristics. The growth of the titer of pneumococcal antibodies in the saliva in the early times of the disease as well as the lack of its changes in blood serum suggest that interaction of pneumococcus with the host is restricted in the given case by the bronchial lumen. PMID- 1408566 TI - [New approaches to evaluation of the inflammatory process in the bronchi of children with bronchopulmonary diseases]. AB - Examination of patients, that included investigation of the clinical, endoscopic and laboratory parameters over time formed the basis for estimating bronchial inflammation. As many as 164 children with recurrent and chronic bronchopulmonary diseases were examined. The authors provide the informative signs allowing one to judge the activity of bronchial inflammation with a high accuracy (up to 90-95%). The complex signs that characterize bronchial inflammation, grades I, II and III, are also provided. The all-round estimation of the inflammatory activity makes it possible to objectively differentiate the status of local homeostasis, which is of paramount importance for administration of adequate and effective therapy. PMID- 1408567 TI - [Working classification of acute respiratory and cardiac insufficiency in young children with pneumonia]. AB - Overall 302 infants with acute pneumonia were examined for gas, acid-base and electrolyte homeostasis, central and cerebral hemodynamics. In interpreting the data obtained use was made of a basically new approach to estimation of central and peripheral hemodynamics, resting on an analysis of gas, acid-base and electrolyte homeostasis, reflecting external respiratory function, blood transport system, redox processes in tissues, and so forth. Based on the data obtained the author has devised the classification of acute respiratory and heart failure as well as rapid index in order to differentiate acute heart and vascular failure in infants with acute pneumonia. PMID- 1408568 TI - [Diagnosis of disorders of rheological properties of blood and central and cerebral hemodynamics in infants with complicated pneumonia]. AB - A study was made of the rheological blood properties, microcirculation, central and cerebral hemodynamics in children of the first year of life with complicated pneumonia. On admission to the department of intensive care and resuscitation the patients demonstrated pronounced hemorheological and hemodynamic disorders which might in many respects determine the disease gravity. Based on an analysis of the clinical observations and hemodynamic findings 3 periods of complicated pneumonia were distinguished in such children: the critical period, stabilization and repair. Each period is characterized by different compensatory adaptive and non adaptive erythrocytic and hemodynamic reactions. PMID- 1408569 TI - [Clinico-pathogenetic characteristics of acute stenosis of the upper respiratory tract in children]. AB - All-round examinations of 484 patients with acute stenoses of the upper respiratory tract revealed two clinico-pathogenetic varieties of the disease: allergic (48.7%) and infectious-inflammatory (51.3%). All the patients demonstrated high allergy whatever the disease variety. The most important laboratory indicators of allergy were as follows: the rise of the index of eosinophilia, of the count of rosette-forming eosinophils in nasal secretion, a high content of total IgE and of allergen-specific IgE-antibodies, attesting to the presence of atopic allergy. These changes were more pronounced in the disease of allergic genesis. The differences in the pathogenesis should be necessarily taken into consideration during treatment administration. In the allergic disease variety, the main approach consists in administration of antihistaminic drugs in addition to the routine treatment measures, whereas in the infectious inflammatory variety, the treatment should also include antiviral agents. PMID- 1408570 TI - [Respiratory function in children with alveolitis]. AB - External respiratory function was examined in 27 patients aged 5 to 17 years suffering from alveolitis. Of these, 10 children were diagnosed to have idiopathic fibrosing alveolitis and 17 exogenous allergic alveolitis. The functional examination included investigation of the static pulmonary volumes by helium dilution method, spirography, body plethysmography, measurements of lung elasticity, diffusion capacity of the lungs and blood gases. It has been established that in alveolitis, restrictive ventilatory disorders prevail, whereas in acute and subacute exogenous allergic alveolitis, obstructive disorders may occur. In all the patients examined, lung diffusion capacity was found to be reduced. PMID- 1408571 TI - [Use of oral antibacterial drugs in the treatment of acute pneumonia in children]. AB - The efficacy of oral antimicrobial agents was studied under conditions of monitored clinical trials. Overall 279 children with different clinical forms of acute pneumonia were entered into the study. It has been shown that the treatment of uncomplicated acute pneumonias may be started since the day of admission to the hospital. The total efficacy of oral drugs was 75%. This does not differ essentially from the efficacy of antibiotics administered parenterally (89%). It has been established that early change (on days 1-3 since the effective treatment) from parenteral to oral administration of antibiotics does not reduce the treatment efficacy but noticeably lowers the injection load of the patients. The side effects (dyspeptic disorders) that occur very frequently during erythromycin treatment suggest that this antibiotic should not be administered to infants. PMID- 1408572 TI - [Tactics in using antibiotics in diffuse forms of chronic nonspecific pneumonia in children]. AB - The authors provide the results obtained during many years of studying different aspects of antibacterial treatment of purulent endobronchitis in children with prevalent forms of chronic pneumonia. The study was attempted at the clinic for disease of childhood, I.M. Sechenov Moscow Medical Academy. Base the complex program of such treatment, which rests on etiotropic , correspondence of the antibiotic administration to the activity of the infectious inflammatory process in the bronchi, and immunomodulating therapy carried out according to indications if any. Introduction of the antibiotic therapy program into clinical practice allowed the attainment of good direct results in 87.6% of patients and of stabilization of endobronchitis in 47% of patients within 1.5 to 3 years. PMID- 1408573 TI - [Value of studying chemiluminescence of blood plasma in the diagnosis of acute suppurative destructive pneumonia in children]. AB - Biophysical studies of the patients' blood plasma have demonstrated that the infiltrative form of acute pneumonia is characterized by appreciable enhancement of fluorescence, the destructive form by its dramatic depression. This rapid method is fairly informative, safe for the patient; it allows the determination of the dynamics of inflammatory and destructive processes that occur in the lungs and the monitoring of the treatment efficacy. PMID- 1408574 TI - [Study of circadian rhythm of bronchial patency for timely correction and evaluation of the effectiveness of inhalation powder forms of salbutamol in children with bronchial asthma]. AB - A study was made of the circadian rhythms of bronchial patency for ++timely correction and dynamic estimation of the efficacy of powdered inhalation salbutamol (ventodisc) in 30 children aged 7-15 years suffering from persistent recurrent bronchial asthma. The treatment with ventodisc was carried out after basic therapy (euphylline or theopec and/or becotid). During 1 week the children inhaled the drug only at the moments of attacks of obstructed respiration. Starting from the 2nd week of the study ventodisc was applied prophylactically bearing in mind the rhythm of the bronchial tone in hours of minimal values of the maximal volumetric rate of expiration (MVRexp). It has been revealed that an optimal approach to ventodisc administration consists in a preventive drug intake arresting asphyxia attacks, inasmuch children with low values of external respiratory function (particularly in cases where MVRexp is less than 50% of normal) during bronchial asthma attacks are not capable of activating the spraying device and taking the whole drug dose. The use of ventodisc in the chronocorrection mode ameliorated the circadian rhythm of the bronchial tone and minimized the drug requirement 2.3-fold. PMID- 1408575 TI - [Acute destructive appendicitis associated with various infectious diseases]. PMID- 1408576 TI - [Oral rehydration in acute intestinal infections in children (clinico-laboratory substantiation and practical use)]. PMID- 1408577 TI - [Use of reaferon and antioxidants in children with chronic hepatitis]. PMID- 1408578 TI - [Errors and hazards in the surgical treatment of children with testicular feminization]. PMID- 1408579 TI - [Immunomodifying properties of human, cow's and mare's milk]. PMID- 1408580 TI - [Various disputable aspects of bronchial obstructive conditions in children]. PMID- 1408582 TI - [The role of genetic and external factors in the development of precursors of arteriosclerosis in children and adolescents]. PMID- 1408581 TI - [Is replacement blood transfusion therapy indicated in children with complicated pneumonia?]. PMID- 1408583 TI - [Prevalence and structure of arterial hypertension among the population of children aged 6-15 years]. PMID- 1408584 TI - [Effect of immunotherapy on the interferon system in children with staphylococcal infection]. PMID- 1408585 TI - [Analysis of comparative effectiveness of various methods of complex therapy of acute glomerulonephritis in children]. PMID- 1408586 TI - [Viral and bacterial associations and their role in the development of bronchopulmonary diseases in children]. AB - Clinical and laboratory criteria for estimating the role of viruses and bacteria that determine bronchopulmonary diseases have been derived. The clinical importance of the detectable microflora, part of which permanently invade the nasopharynx (pneumococcus, adenoviruses) is under critical review. Pneumonias that may develop within the first days of acute respiratory viral infection are characterized by monoviral influenzal or RS-infection; later pneumonias are marked by viral infection with the predominance of adenoviruses. Attempt has been made to reveal the role of geno- and phenotypic factors (N-acetylation, lipid peroxidation, synthesis of alpha-interferon). The data obtained support an assumption about self-regulation of the child's immune system and the adaptation character of responses in mixed infections. PMID- 1408587 TI - Effects of progressive exercise on attentional focus. AB - To replicate 1986 work of Salmela and Ndoye on whether physical arousal from riding a stationary bicycle led to narrowing of attentional focus 17 subjects responded to a verbal 5-choice RT task while pedalling to exhaustion. Increased heart rates with increased physical stress (bicycle resistance increased) was not associated with narrowing of attention. When heart rates were 160 and 180 bpm, RTs to stimuli peripherally located to the right were slower than central ones. Further evaluation is required. PMID- 1408588 TI - Effect of aerobic exercise on negative affect, positive affect, stress, and depression. AB - Three groups of subjects, 15 Longer-term Exercisers, 14 Short-term Exercisers, and 18 Nonexercisers completed questionnaires designed to measure negative affect associated with thoughts, negative affect associated with day-to-day experiences, positive affect associated with thoughts, and positive affect associated with day to-day experiences, depression, and stress. All the subjects also provided a rating of their over-all general stress. The Longer-term Exercisers reported more positive affect associated with their thoughts and day-to-day experiences than the Nonexercisers. There also was a trend for the Longer-term Exercisers to report less over-all stress than the Nonexercisers. PMID- 1408589 TI - Fast music causes fast drinking. PMID- 1408590 TI - Grip strength and fatigue in junior college tennis players. AB - Change in grip strength over 30 trials was documented in two samples of junior college tennis players to assess possible fatigue. Eight men and eight women performed 30 maximum-grip strength tests with 25-sec. rests between trials. Significant positive correlations (.38 and .53 for men and women) were observed between grip strength and trials. In practical terms, grip strength did not change over 30 trials in these tennis players. The data suggested that the repetitive gripping patterns used by these players in tennis play resulted in consistent maximum-grip strengths across 30 trials. PMID- 1408591 TI - Psychometric properties of the Learning-Orientation Grade-Orientation II Scale. AB - The Learning-Orientation Grade-Orientation Scale of Eison, Pollio, and Milton was administered to 85 college students and analyzed to study the psychometric properties of the instrument. Scale means were consistent with those usually reported. Cronbach coefficients alpha for 5 of the 6 scales ranged from .58 to .70; however, the coefficient alpha for learning-orientation attitude scale was questionably low (.29). Item analyses and factor analyses support the continued use of at least 5 of the 6 scales measured by the inventory. PMID- 1408592 TI - Children's development of reaching: temporal and spatial aspects of aimed whole arm movements. AB - Age-related changes in movement time and spatial distribution of pointing errors were investigated using a whole-arm target-aimed task. 60 children (6 to 11 yr.) and 10 young adults were required to reach towards targets located on a vertical screen in four conditions: target lit for 4 sec. in light (1), in darkness (2), target lit for 200 msec. in light (3), in darkness (4). Accuracy was perfect in Conditions 1 and 2, with a significant increase of MT in Condition 2 between the ages 7 and 10. Accuracy decreased slightly in Condition 3 and strongly in Condition 4, despite a similar shortening of MT. In Condition 4 the subjects undershot the target position: horizontally from age 8 and vertically in all age groups, with an increase of vertical bias by girls at age 9. These results suggest age-related changes in computation of arm movement towards the target. PMID- 1408593 TI - Bibliography of the psychometric properties of the Bender Visual-Motor Gestalt Test: 1970-1991. PMID- 1408594 TI - Nurses' attitudes toward obese persons and certain ethnic groups. AB - Societal attitudes toward obese persons are predominantly negative, and many health care professionals share these beliefs. This study compared attitudes toward obese persons of 67 US nurses to those of 107 Canadian nurses. Also, attitudes toward obesity were examined as a particular class of prejudice. A positive correlation was hypothesized between ethnic prejudice and prejudice regarding obese persons. Significant differences in attitudes toward obese patients were observed between the two groups on several questionnaire items, and the hypothesis was confirmed by the moderate r of .53 for US nurses. A surprising finding was a new target of ethnic prejudice: the Caucasian majority. PMID- 1408595 TI - Effects of instruction and practice on ball catching skill: single-subject study of an 8-year-old. AB - An eight-year-old boy learned to make one-handed catches by involvement in three 30-min. periods of instruction and practice consisting of modelling, videotape based performance feedback, and variable practice interspersed with videotaped assessments on seven consecutive days. An adult-like catching action (both hands) emerged in the second session and was used exclusively thereafter. Catching success at the second and third assessments improved from 40% (preferred hand) and 30% (non-preferred) to over 90% (both hands) on the final assessment. Following the intervention, success and the catching action were similar to those of skillful ten-year-old subjects observed in a previous study. PMID- 1408596 TI - Bulimic symptomatology and coping in a nonclinical sample. AB - This study examined the relationship between bulimic symptomatology as measured by scores on the Bulimia Test--Revised and coping orientation as measured by Endler and Parker's Coping Inventory for Stressful Situations given to a nonclinical sample of 164 female college students. A relationship was obtained among emotionally oriented coping, task-oriented coping, and scores on the Bulimia Test. PMID- 1408597 TI - Imagined test situations produce contextual memory enhancement. AB - Two groups of 12 undergraduates learned a 26-item list of medium-imagery words. Those who visualized an examination-hall scored better at 1-wk. recall than those who visualized countryside during learning, thereby providing confirmation of the context-dependency effect. PMID- 1408598 TI - Effect of memory set-size upon event related potentials for concrete and abstract kanji stimuli. AB - Event related potentials (ERP) and reaction times (RT) were recorded during the performance of memory-retrieval tasks using the Japanese kanji characters. P300 latency and RT increased as the memory set-size increased. The slope differences between RT and P300 latency were larger for stimuli when concrete kanji were used than when abstract kanji were used. This suggests that, in memory search, the 20 subjects were likely to employ direct lexical access when processing concrete kanji and likely to use phonetic coding when processing abstract kanji. PMID- 1408599 TI - EEG alpha activity and hallucinatory experience during sensory deprivation. AB - The relationship between hallucinatory experiences under sensory deprivation and EEG alpha activities was studied. Each of seven male students lived alone in an air conditioned, soundproof dark room for 72 hours. When hallucinatory experiences occurred, the students pressed a button at once. If they could not press the button during the experience, they were required to press it two times when the hallucinatory experience was finished. Spectral analysis was performed on the consecutive EEG samples from just before button-presses to 10 min. before them, and the average alpha band amplitudes were obtained for the four epochs (0 .5, .5-2, 2-5, 5-10 min.). For the single button-presses, the amplitude of alpha band increased 2 min. before the button-presses. Right-hemisphere EEG activation was observed in the occipital area for the double button-presses. The results suggest an association between the hallucinatory experiences under sensory deprivation and the amount of EEG alpha activity. PMID- 1408600 TI - Training Special Olympics athletes: a pilot study. PMID- 1408601 TI - Resistance of voice onset time variability to intoxication. AB - Voice onset times of /d/ and /t/ were measured for 16 adult subjects (age range 21 to 26 years) under conditions of sobriety and intoxication. Subjects consumed beer to reach intoxication levels between 0.075 and 0.100% as measured using a portable breathalyzer test. Analysis indicated consistent variabilities over time for each subject and resistance of VOT variability to alcohol influence. PMID- 1408602 TI - Reliability of the amplitude of the return-sweep velocity of eye movements during reading. AB - A Beckman Type RM Dynograph was used to record the eye movements of 26 professional college men, once without spectacle corrections and then with plano lenses on a trial frame, during reading equivalent print at a distance of 33 cm. Amplitudes of the return-sweep velocity on these two trials were used to calculate an equivalent form reliability coefficient. A Pearson r of 0.88 indicates that their reliability is moderately high, meaning that both the desirable as well as the undesirable reading habits are probably deeply rooted by college, and imply that any reading remediation or improvement training should be performed at some much earlier stages to be efficiently effective. PMID- 1408603 TI - Memory disadvantages for CVC associates of emotional words. AB - A paired-associate task (word-CVC) performed by 40 subjects confirmed that associates to active emotional words were less well remembered than associates to neutral words or pleasant or unpleasant ones. Results are interpreted as satisfactorily explained by differences in the activation of network nodes if such differences were in turn affected by the arousal characteristic of the words. PMID- 1408604 TI - Three-dimensional interpretation of quadrilaterals. AB - The three-dimensional interpretation of two-dimensional images was studied by using quadrilateral patterns, and some relationships between their structure, depth, and shape interpretations were analyzed under various viewing conditions. We defined rectangular and nonrectangular viewing conditions as follows: the viewing condition in which the quadrilateral, including parallel sides, could be a projection from a rectangle and the viewing condition in which it could not be so. For 9 subjects, 10 measurements were made in each experiment. Analysis showed that a pair of parallel sides of a quadrilateral were viewed as parallel to the viewer's forehead when the sides were horizontal in the image plane and were seen as slanting in depth if they were slanted in the image plane. The quadrilateral composed of parallel and nonparallel sides was perceived as rectangular when viewed with foveal vision even though under the nonrectangular viewing condition, if that viewing condition was not so different from the rectangular viewing condition. The quadrilateral did not appear to be rectangular when viewed in peripheral vision even though the rectangular viewing condition was used. PMID- 1408605 TI - Perceptual-motor coordination and style in healthy boys and those with minimal brain dysfunction. AB - Differences in visual-motor tracking by 8- to 9-yr.-old boys diagnosed with Minimal Brain Dysfunction or healthy have been analyzed. The subject's task was to use two computer keys to control a cursor line within a target which moved horizontally in two directions over the display. Target size and speed were the experimental variables. Off-target incidences and durations were measured and evaluated. The latter were longer and the former were more frequent on small targets for boys with brain dysfunction than for healthy boys. The two measures correlated negatively in most situations. The perceptual-motor style expressed by means of the distribution of coincidences of the two measures being over or under a criterion set equal to the corresponding averages of the healthy boys was different in the two groups. Brain-damaged boys were characterized mostly by the combination of high incidence of low duration misses for small and fast targets and by high incidence of high duration misses for large and slow targets, whereas most healthy boys showed a few misses of low duration for large and slow targets and few misses of high duration for small and fast targets. PMID- 1408606 TI - Postural sway characteristics of single leg stance in men with mental retardation. AB - This study examined the postural sway characteristics of 10 men with mental retardation and 10 each normal men and women during the one-legged stance test. Significant differences between the men with mental retardation and the other two groups were found on measures of lateral sway and on the sagittal sway:lateral sway ratio. PMID- 1408607 TI - Diagnosing MPD with two new Rorschach signs: are the signs valid or are the MPDS atypical? AB - The validity of newly developed "Splitting" and "Dissociative" signs on the Rorschach for diagnosing multiple personality disorder (MPD) was questioned. It was pointed out that the mean number of Rorschach responses for what were ostensibly patients with MPD was so high as to render the sample atypical. It was suggested that perhaps the Splitting and Dissociative signs were diagnostic of either dissociation in general or MPDs who have experienced decompensation, leading to hospitalization. PMID- 1408608 TI - Specific and diversive curiosity in gifted elementary students. AB - Twenty-nine gifted students in Grades 2 to 6 from the small school districts in north central Kansas completed the Maze test and the Which-to-Discuss test. Background information such as age, sex, grade, and marital status of parents was also collected. There were no significant differences between boys and girls or for students from divorced and nondivorced parents on either the Which-to-Discuss test (specific curiosity) or the Maze test scores (diversive curiosity). The students scored significantly higher on the former test than chance guessing which suggests the students were displaying specific curiosity. Scores of these gifted students on these two tests of curiosity were significantly and positively correlated. PMID- 1408609 TI - A simple method for evaluation of Rorschach Imagery Reactivity. AB - A general scoring system, previously developed for the analysis of pictorial associations within the paradigm of Visual Imagery Sequences, was applied in the evaluation of visual associations to memory images of Rorschach inkblots (Imagery condition) in a comparison with standard Rorschach responses (Conventional condition). The participants, 80 consecutively selected psychiatric outpatients, were divided into Clinical Reactor and Nonreactor groups, according to how productive they were of psychodynamically revealing material during insight oriented therapy using imagery. For this simple scoring method (which does not include the customary Rorschach scores), conclusions concerning Imagery Reactivity in the Rorschach agreed with those of previous studies using a scoring system more unique to the Rorschach. The inferences drawn from statistical analysis by groups and conditions also contribute additional refinements to the understanding of the subtle interplay between defensiveness and sensitivity to imagery in determining the patterns of scorable components within the response complex. This general scoring method correctly identified 95.6% of Imagery Reactors and 100% of Imagery Nonreactors, an improvement over the 87% efficiency of the previously described, Rorschach-based method for assessing Imagery Reactivity in the Rorschach. PMID- 1408610 TI - Priming outside of awareness and subsequent stimulus identification. AB - The influence of priming outside of awareness on performance of a color recognition task was investigated. Using a tachistoscope, a color word that matched ("congruent prime") or did not match ("incongruent prime") the target color or a blank prime was followed by a pattern mask and the target color. Identification performance was superior on the blank prime trials to the congruent prime trials, with performance on the incongruent prime trials being the lowest. A subsequent study included a meaningless (XXX) prime condition, and it was found that meaningless primes interfered with target-color identification more than the congruent and blank prime conditions, but less than the incongruent prime condition, suggesting that primes, in addition to producing semantic activation, impose demands on information-processing capacity of the perceptual system. PMID- 1408611 TI - The stability and variability of suicide rates in the states of the USA. AB - The suicide rates of the American states in 1918-1922 were only weakly associated with the rates in 1980. The mean rate had not changed by 1980, but the standard deviation of the rates had decreased. PMID- 1408612 TI - Differences in lingual vibrotactile threshold shifts during magnitude-estimation scaling between normal-speaking children and children with articulation problems. AB - The purpose of this study was to investigate differences in function of the tactile sensory system between groups of normal-speaking children and children with articulation problems. This task was accomplished by studying possible tactile threshold shifts occurring during magnitude-estimation scaling of vibratory stimuli presented to the dorsal surface of the tongue. 10 normal speaking children (M age = 7.8 yr.) and 9 children with articulation problems (M age = 7.5 yr.) participated. The normal-speaking children and articulatory defective children performed differently on the magnitude-estimation scaling task in which threshold was allowed to return to baseline after each stimulus presentation. These two groups of children also showed dissimilar threshold shifts for the suprathreshold intensities employed in the magnitude-estimation scaling. PMID- 1408613 TI - Formation of arbitrary stimulus classes in matching to complex samples: supplementary data. AB - A follow-up study of work published in 1990 showed that consistent use of Tone relevant trials during training and testing baselines contributed to the reliable formation of 5-member stimulus classes during matching to sample. With Tone irrelevant trials during either training or testing 4 of 12 subjects formed such classes, but none did so when such trials were used in both training and testing baselines. This extends our prior work. PMID- 1408614 TI - Automatisation deficits in balance for dyslexic children. AB - Traditional theories of dyslexia have focused on components of the reading process. The Dyslexic Automatisation Deficit hypothesis takes a broader view, attributing deficits to an inability to become completely fluent in cognitive and motor skills. A series of experiments compared the balance of 15-yr.-old and 11 yr.-old groups of dyslexic children and normal children matched for age and IQ under single-task and dual-task conditions. There were no group differences in the single-task conditions. However, introduction of a concurrent secondary task led to a dissociation in that, whereas the balance of normal children was unaffected, the dyslexic children's balance was significantly impaired. It was concluded that the normal children balanced automatically whereas the dyslexic children did not. These results directly support the proposed framework. PMID- 1408615 TI - The Emotions Profile Index and locus of control. PMID- 1408617 TI - Anxiety and color saturation preference. AB - The relationship between personality characteristics and color preference was investigated. Of 49 women and 17 men, 30 individuals scoring above the mean on an anxiety scale preferred significantly less saturated colors than 36 individuals scoring below the mean. PMID- 1408616 TI - Biases in perception and reporting following a perceived toxic exposure. AB - Reactions to chemical exposures often include fears of future illness, cancerphobia, reports of multiple chemical sensitivity, and other ill-defined complaints. Frequently, these complaints occur at levels of exposure not known to cause physiological harm. Although frequently dismissed as hysterical or hypochondriacal reactions, these complaints, along with other indefinite symptoms, may be better understood in terms of biases in perception and reporting. In this paper, we outline various sources of perceptual and response biases including prior beliefs, the media, influential others, reconstructed personal histories, self-perceptions, and the forensic environment. It is recommended that a thorough understanding of symptom-reporting and psychological distress following a chemical exposure involves consideration of these issues. PMID- 1408618 TI - Left ear (right temporal lobe) suppressions during dichotic listening, ego-alien intrusion experiences and spiritualistic beliefs in normal women. AB - Beliefs in spiritualism, a history of a sensed presence, and mental diplopia may share a common source of psychometric variance. We hypothesized that this variance should be specifically associated with right temporal-lobe function. Inferences of temporal lobe signs, hemisphericity (Vingiano's quotient) and self esteem as well as dichotic listening measures were obtained for 26 university women. As predicted, the numbers of left-ear suppressions (right temporal-lobe function) but not of right-ear suppressions were specifically and moderately (rho = 0.64) correlated with the intensity of Tobacyk's spiritualistic beliefs and a history of sensed presences and ego-alien intrusions. However, the negative association (rhos about -0.45) between indices of left-right hemisphericity and self-esteem was related to a separate factor. PMID- 1408619 TI - Perceived level of stress among university undergraduate students in Edmonton, Canada. AB - A sample of 457 (177 men, 280 women) undergraduate students were surveyed regarding perceived level of stress. Women were more likely than men to report an unacceptable stress level. To reduce stress, women were more likely to indicate a need to limit commitments, exercise, and worry less. Reasons for not reducing stress were lack of time and lack of self-discipline, both of which were reported significantly more often by women. The present data suggest health education interventions are needed to assist students in coping with the stress they experience. PMID- 1408620 TI - Effects of contextual interference on learning technical sports skills. AB - The effects of contextual interference on learning skills of volleyball (volley, bump, serve) are influenced by the scheduling of actual practice sessions: the activities can be proposed in a repetitive practice schedule (blocked practice) by continuously repeating the same task (low interference) or in random practice schedules by performing more tasks or variations of one same activity (high interference). High contextual interference, even though causing immediate limited performance, leads to superior performance on retention and transfer tests. Four experimental groups (13 students each) were placed in conditions of random, blocked, serial, and serial with high interference practice for 8 meetings (2 tests and 6 practice). Analysis yielded significant differences among the groups on a transfer test (long transfer) for the serve, so results in this instructional setting are partially in line with those generally found in laboratory experiments. PMID- 1408621 TI - Association of attitude toward mathematics with self-efficacy, causal attribution, and personality traits. AB - 983 children from Grades 1, 2, and 3 of the middle schools participated as subjects. Of these, 339 children were judged as having higher "self-efficacy" than the others. The associations of attitude toward mathematics with self efficacy, attributions, and personality traits measured on the Shimoda Personality Inventory were investigated. Analysis showed that attitude toward mathematics had significant effects on mathematics performance. In attribution of effects to mathematics performance there were differences among the children across the grades. Among personality traits the immodithymic trait was significantly correlated with attitude toward mathematics. PMID- 1408622 TI - Right hemisphericity, low self-esteem, and unusual experiences: a response to Vingiano. AB - Vingiano's (1992) challenge concerning the relationship between right hemisphericity, low self-esteem, mystical experiences, and religiosity can be clarified by the concept of vectorial hemisphericity. Ontogenetic intrusions of right-hemispheric processes into the left hemispheric sense of self should be experienced most frequently as an apprehensive "presence" that results in lower self-esteem. Because transient above-normal left-hemispheric activity enhances positive affect and the sense of self, concurrent right-hemispheric intrusions are experienced as mystical experiences. Religiosity would be the consequence of persistent above-normal left-temporofrontal activation that encourages the delusion. Hence, extreme conditions, such as left lateralized temporal-lobe epileptic foci, encourage both mystical and religious experiences. PMID- 1408623 TI - Language ability and sex affect humor appreciation. AB - Subjects (63 men and 63 women) completed a humor appreciation scale and 20 trials on a word-recognition task using a divided visual field. Factor analysis extracted eight factors from the humor scale most of which differentiated subjects on the basis of liking for various humorous contents including disparagement and non-sense humor. Subsequent analyses showed that greater liking for specific types of humor was associated with basic language abilities. The results also support sex differences in humor preferences and Freud's tripartite taxonomy of humor contents. PMID- 1408624 TI - Sex differences in suicide notes. PMID- 1408625 TI - Clinical versus actuarial prediction: a review of the literature. AB - Decisions made by psychologists can have considerable consequences on people's lives. Their decisions could be based on clinical judgment or empirically derived formulas. These two alternatives created a controversy concerning clinical and actuarial prediction. This controversy has been in existence for almost 70 years. During this time hundreds of articles have been published on this topic. This paper contains a review of the findings and issues on clinical versus actuarial prediction. The main conclusions are that (1) linear models are superior to other mathematical models of human judgment, (2) actuarial methods are more accurate than clinical prediction in many situations, (3) human judgment is flawed, and (4) actuarial methods are rarely employed in practice for a variety of reasons. PMID- 1408626 TI - Motivation needs of sampled Fortune-500 CEOs: relations to organization outcomes. AB - Motive scores (needs for Achievement, Affiliation, and Power) of the chief executive officers of the nation's 50 largest industrial firms were determined using content analysis of letters to stockholders contained in the firms' annual reports. The scoring method was a modification of the standard TAT scoring procedure. Results showed that chief executive officers' high need Achievement was correlated with relative growth in sales, while high need Power was correlated with relative growth in profits. Effects of need Achievement and need Power also were examined for return on equity and return on sales. Implications are discussed. PMID- 1408627 TI - Splitting as a predictor of depression. AB - 146 university students completed measures of splitting, depression, and self esteem. Splitting was positively correlated with depression and negatively related to self-esteem. PMID- 1408628 TI - To what extent do interactive pictures promote recall? AB - In four experiments, a total of 352 subjects viewed word pairs alone or accompanied by pictures, after which they were given a cued-recall test. Although Exps. 1 and 2 showed that recall of brand names was similar with separate and with interactive pictures, it was argued that the latter provided a cue enabling subjects to combine the separate components mentally. In Exp. 3, recall of both low concrete nouns and brand names was enhanced with interactive pictures and the effect was replicated in Exp. 4 with subjects who were learning English. These results offer hope to advertisers who wish to use interactive pictures whose relationship to their names is indirect. PMID- 1408629 TI - Neuropsychological performance and suicidal behavior in adult psychiatric inpatients. AB - Although various studies have shown that suicidal persons exhibit greater cognitive deficiencies than both normals and other psychiatric patients, researchers as yet have been unable to account for the source(s) of the differences. Some of these differences (e.g., cognitive rigidity and impaired problem solving) hint of possible organic involvement. This study explored the relationship of neuropsychological functioning to suicidal behavior by comparing 20 suicidal and 27 nonsuicidal psychiatric inpatients on several tests of neuropsychological functioning. Although results showed no significant differences between the two groups on most measures, both groups showed evidence of notably high levels of cortical dysfunction relative to test norms. Thirty five percent of suicidal patients and 44% of nonsuicidal patients scored in the impaired range. Implications of this high frequency of impairment for the treatment of suicidal and nonsuicidal psychiatric patients are discussed. PMID- 1408630 TI - Still no evidence for a photoreceptor-level abnormality in dyslexia. PMID- 1408632 TI - Informativeness and the learning of bipolar adjectives. AB - The effects of informativeness upon the learning of bipolar adjectives were examined by asking 20 preschoolers to learn novel words descriptive of different lengths vs tensions of a coiled spring. The set of adjectives which contrasted most highly for informativeness showed the greatest asymmetry for successful learning. PMID- 1408631 TI - Trading accuracy for speed: gender differences on a Stroop task under mild performance anxiety. AB - A standard Stroop task was used to examine the effect of performance anxiety on 58 male and 69 female undergraduates. Subjects were approached either by two casually dressed experimenters who did not stress speed or accuracy or by 4 or 5 formally dressed experimenters who stressed quick and accurate performance. Subjects were told the test would assess their "mental acuity"; their responses were visibly tape-recorded. Reaction times did not show differential response by anxiety condition; men and women showed different RTs only in the low-anxiety condition, with women performing significantly more slowly. There were no significant differences for the high-anxiety condition. Analysis of errors showed women were more accurate than men. Men traded accuracy for speed and may have been under equal performance stress in both situations. When performance was not stressed, women were slower and more accurate than men. When performance was stressed, women increased their speed to match that of men while maintaining their greater accuracy. PMID- 1408634 TI - Experimental stimulation by burst-firing weak magnetic fields over the right temporal lobe may facilitate apprehension in women. AB - Intermittent bursts of weak magnetic fields whose patterns simulate normal amygdaloidal-hippocampal activity were generated by computer over the right or left temporal regions of men and women during partial sensory deprivation. As predicted, women but not men reported greater apprehension during right hemispheric but not left-hemispheric stimulation. Intrusions of right-hemispheric processes have been hypothesized to affect self-esteem adversely. These results also support the role of the right parahippocampal region in the production of panic attacks. PMID- 1408633 TI - Longitudinal reliability of the Life Satisfaction Index (Short Form) with nursing home residents: a cautionary note. AB - We administered the Life Satisfaction Index (Short Form) 18 times over a 39-wk. period to an initial sample of 76 old, frail, multiply impaired, and depressed nursing home residents participating in a longitudinal quasi-experimental study of the effects of cognitive group interventions on cognition and depression. As no changes over time were observed on the outcome variable of life satisfaction, the stability of the instrument's internal consistency could be examined. Kuder Richardson KR-20 coefficients ranged from .11 to .60, with a mean of .42 (SD = .11). We conclude that caution should be used when applying this instrument to measure life satisfaction in frail nursing home residents. PMID- 1408635 TI - The orientation of a parallel-line texture between the verticals can modify the strength of the Poggendorff illusion. AB - In the present experiments, we attempted to evaluate the modification of the strength of the Poggendorff illusion as a function of the different orientation of a parallel-line texture filling the space between the vertical lines. In Experiment 1, the standard version of the Poggendorff configuration was tested against four different parallel-line textures oriented at 0 degrees, 45 degrees, 90 degrees, and 135 degrees with respect to the obliques. The results showed that the illusory effect was a linear function of the progressive discrepancy between the angle of the lines of the texture and that of the obliques. In Experiment 2, we tested the same textures used in Experiment 1 after the elimination of the two vertical lines. The data obtained approximated a linear function, as in the previous experiment, but the alignment errors were consistently lower. The statistical analysis performed on the data of all eight experimental conditions shows that both factors--texture and presence/absence of verticals--were significant, but most of the effect was due to the texture factor. The results may be interpreted through the "perceptual compromise hypothesis," originally proposed for the bisection forms of the Poggendorff illusion, but with important modifications. The data are also discussed in terms of their implications for other theories proposed for the Poggendorff illusion. PMID- 1408636 TI - Contextual and sequential effects on judgments of sweetness intensity. AB - Presenting stimuli from skewed concentration distributions affects mean responses on category scales. However, if the number of categories on the response scale is increased, the degree of separation between the mean responses obtained for a positively as opposed to a negatively skewed concentration distribution diminishes. The present study investigates the effect of skewed concentration distributions upon ratings on a line scale and compares it to the context effect found for a 7-point category scale. In addition, sequential dependencies between consecutive stimuli and responses are investigated in order to assess their relevance in taste-intensity scaling studies. The context effects are similar for the 7-point category scale and for the line scale. The analyses of sequential effects show that both preceding responses and preceding stimuli affect current responses. However, since these two factors work in opposite directions, only a small contrast effect from the previous stimulus is significant in an overall analysis. The present study shows that even though the overall sequential effects between consecutive stimuli and responses are small, the effect of experimental context may be considerable. Since subjective context is established at the beginning of a session and sequential dependencies operate throughout the whole session, it is argued that contextual and sequential effects are only indirectly related. PMID- 1408637 TI - Structural alterations of an ambiguous musical figure: the scale illusion revisited. AB - The scale illusion (Deutsch, 1975) shows the importance of frequency range in the perceptual organization of a sequence of notes. This paper includes three experiments on the scale illusion. Experiments 1 and 2 demonstrated that if the structure of the pattern of notes used in the original scale illusion study is altered slightly, by adding or subtracting a pair of notes from the ends of the sequence, there is a significant decrease in the rate of frequency-based responses, suggesting a weaker illusion. Experiment 3 investigated two features of the note patterns that may have led to this change. Specifically, it asked whether the decrease in the strength of the illusion is due to (1) the nature of the notes at the extremes of the frequency range and/or (2) the nature of the notes at the crossing point of the two scales. While both sources were found to affect the strength of the scale illusion, the former had a greater influence. PMID- 1408638 TI - Parallel discrimination of subjective contours defined by offset gratings. AB - Recent physiological studies (von der Heydt & Peterhans, 1989) suggest that the orientation of subjective contours is encoded very early in the visual system (V2 in monkey). This result is seemingly at odds with existing psychophysical data which suggest that the detection of subjective contours involves selective attention. It is argued that certain subjective contours are registered in a reflexive (bottom-up) manner by the visual system but that selective attention may be needed to gain access to this representation. To assess this suggestion, a visual-search task was used in which subjects were to detect the presence of a horizontal (vertical) subjective contour (defined by offset gratings) in a variable number of vertical (horizontal) subjective contours (also defined by offset gratings). When there were no competing organizations within the display, detection was indeed independent of the number of nontarget distractors, that is, selective attention was unnecessary. In a second experiment, we found that a curved form (a crescent defined by subjective contours) was easier to detect in a background of vertical bars (also defined by subjective contours) than vice versa, namely, a search asymmetry paralleling those found by Treisman and Gormican (1988). A final experiment showed that when the horizontal and vertical bars of the first experiment formed textured regions, they could be discriminated at very brief display durations (30-120 msec). However, when the line terminations aligned along the subjective contour were tapered rather than abrupt, discrimination dropped off with the degree of tapering. The latter result is consistent with the assumption that the registration of subjective contours in V2 involves the integration of responses from aligned, end-stopped cells found in V1 (von der Heydt & Peterhans, 1989). PMID- 1408640 TI - Measuring the effect of multiple eye fixations on memory for visual attributes. AB - Because of limited peripheral vision, many visual tasks depend on multiple eye fixations. Good performance in such tasks demonstrates that some memory must survive from one fixation to the next. One factor that must influence performance is the degree to which multiple eye fixations interfere with the critical memories. In the present study, the amount of interference was measured by comparing visual discriminations based on multiple fixations to visual discriminations based on a single fixation. The procedure resembled partial report, but used a discrimination measure. In the prototype study, two lines were presented, followed by a single line and a cue. The cue pointed toward one of the positions of the first two lines. Observers were required to judge if the single line in the second display was longer or shorter than the cued line of the first display. These judgments were used to estimate a length threshold. The critical manipulation was to instruct observers either to maintain fixation between the lines of the first display or to fixate each line in sequence. The results showed an advantage for multiple fixations despite the intervening eye movements. In fact, thresholds for the multiple-fixation condition were nearly as good as those in a control condition where the lines were foveally viewed without eye movements. Thus, eye movements had little or no interfering effect in this task. Additional studies generalized the procedure and the stimuli. In conclusion, information about a variety of size and shape attributes was remembered with essentially no interference across eye fixations. PMID- 1408641 TI - Framing effects and the reversed Muller-Lyer illusion. AB - The enclosure hypothesis of the reversed Muller-Lyer illusion was examined in three experiments. In Experiment 1, the ingoing- and outgoing-wings forms of the illusion were measured separately, as a function of the size of the gap between the ends of the shaft and the apices of the wings. In Experiments 2 and 3, the effects of a square frame and of complete and amputated versions of a rectangle on the perceived length of an enclosed horizontal line were examined. For all non Muller-Lyer illusion figures, an inverted U-shaped function describes the relationship between illusion magnitude and the length of the test line. The peak overestimation of the test line's length was obtained when the ratio of total figure length to test line length was about 3:2. Taken together, the results of the three experiments suggest that the reversed Muller-Lyer illusion can be explained within current theoretical frameworks, such as assimilation theory, without recourse to a special factor of enclosure. PMID- 1408639 TI - Visual attention and perceptual grouping. AB - Perceptual organization is thought to involve an analysis of both textural discontinuities and perceptual grouping. In earlier work, we found that textural discontinuities were detected normally even when visual attention was engaged elsewhere. Here we report how perceptual grouping is affected when visual attention is engaged by a concurrent visual task. To elicit perceptual grouping, we used the Gestalt demonstrations of grouping on the basis of proximity and of similarity. Four tasks were investigated, some requiring the observer to discriminate between horizontal and vertical grouping, and some requiring the observer to merely detect the presence or absence of grouping. Visual attention was engaged at the center of the display by a form identification task. The detection of a textural discontinuity served as a control task. Concurrent form identification conflicted with all four grouping tasks, resulting in a significant reduction of grouping performance in each case. No performance reduction was observed when either form identification or grouping discrimination was combined with the detection of a textural discontinuity. These results suggest that perceptual grouping and form identification compete for visual attention, whereas the detection of a textural discontinuity does not. PMID- 1408642 TI - Letter visibility and word recognition: the optimal viewing position in printed words. AB - It has repeatedly been shown that the time and accuracy of recognizing a word depend strongly on where in the word the eye is fixating. Word-recognition performance is maximal when the eye fixates a region near the word's center, and decreases to both sides of this "optimal viewing position." The reason for this phenomenon is assumed to be the strong drop-off of visual acuity: the visibility of letters decreases with increasing eccentricity from fixation location. Consequently, fewer letters can be identified when the beginning or ending of a word is fixated than when its center is fixated. The present study is a test of this visual acuity hypothesis. If the phenomenon is caused by letter visibility, then it should be sensitive to variations of visual conditions in which the letters are presented. By increasing the interletter distances of the word (e.g., a_t_t_e_m_p_t), letter visibility was decreased. As expected from our hypothesis, the viewing-position effect became more exaggerated. An additional experiment showed that destroying word-shape information (e.g., aTtEmPt) decreased overall word-recognition performance but had no influence on the viewing-position effect. Varying the viewing position in words might thus be used as a paradigm, allowing one to separate out the contribution of letter information and supraletter information to word recognition. PMID- 1408643 TI - Geometrical haptic illusions revisited: haptic illusions compared with visual illusions. AB - Revesz (1934) reported that haptic illusions were observed in almost all of the geometrical optical illusion figures. The present study reexamined seven geometrical illusions in both haptic and visual modes. In the Muller-Lyer, Ponzo, and vertical-horizontal figures, haptic illusions equivalent to the visual illusions were observed. In the Oppel-Kundt figure, a haptic illusion similar to the visual one was obtained. In the haptic Delboeuf stimuli, the size illusion of the outer circle occurred, whereas that of the inner circle did not. No haptic illusion was obtained in the Poggendorff figure. In the Zollner figure, a haptic illusion directionally opposite to the visual one was obtained. These results show that haptic illusions do not occur in all of the geometrical illusion figures. They also suggest that haptic illusions are not necessarily mediated by visualization and that haptic processing of the figures often occurs in a manner different from vision. PMID- 1408644 TI - Oculomotor readiness and covert orienting: differences between central and peripheral precues. AB - The costs produced by invalid precues can depend on the spatial relationship between the cued location and the target location. If oculomotor programs mediate attention shifts, then the effect of varying the spatial relation between the cue and target should be the same for covert orienting (indexed by manual responses) and saccadic responses. We found this to be true only for central precues. With central precues, both manual and saccadic costs were greater when cue and target occurred on opposite sides of the vertical meridian than when they occurred on the same side. With peripheral precues, there were no meridian effects in either response condition, but there was a significant dissociation in the pattern of saccadic and manual costs. For manual responses costs were greater when the target was eccentric relative to the cue, whereas for saccades costs were greater when the cue was eccentric to the target. These results provide additional support for the idea that different orienting mechanisms are engaged by central and peripheral precues. They further suggest that the relationship between oculomotor and attentional orienting may depend on the nature of the precue, with the potential for interdependence being greater with central precues. PMID- 1408645 TI - Production of time intervals from segmented and nonsegmented inputs. AB - One important factor influencing the accuracy of a timing estimate is the counting activity that a human subject may adopt. In the present study, the usefulness of this activity is evaluated with a strategy whereby subjects are presented segmented and nonsegmented intervals, before they start to produce a series of these intervals, using a finger-tapping procedure. The results are mainly analyzed in the light of Killeen and Weiss's (1987) model, which addressed this question of counting. The results revealed that (1) a scalar property gives a better description of the pacemaker activity than does a Poisson process, and (2) an optimal timing performance would be reached with the utilization of subintervals with an approximate value of 400 msec. Finally, the discussion also incorporates an analysis of the variability related to the motor component in a tapping task. PMID- 1408646 TI - Resolving the control struggle on an eating disorders unit. AB - The authors describe the process by which the nursing staff of an eating disorder program was able to identify an ineffective treatment model and to implement some needed changes. They describe the Therapeutic/Administrative Split Model, a method to improve communication and treatment planning between the nurse and psychiatrist. How family control issues are mirrored in the treatment process, and played out within the transference, are also explored. PMID- 1408647 TI - Clozapine: nursing care considerations. AB - Since its release for clinical use in February of 1990, an ever-growing number of psychiatrists are beginning to use clozapine to treat clients whose psychoses have been refractory to conventional measures. While clozapine has been shown to have superior antipsychotic efficacy without the standard extrapyramidal side effects, it also has some potentially fatal side effects. The unpredictability in client response poses a number of issues for nursing, which has an essential role in assuring that treatment occurs accurately and safely. The authors share their experience in working with clients, families, and staff over the past two years who have been actively involved with clozapine. PMID- 1408648 TI - Correlating nursing care, nursing practice, and nursing performance standards. AB - All too often nursing standards have been viewed as a cumbersome paperwork task with little day-to-day practical relevance. Using a matrix approach that incorporates nursing role functions and the nursing process, the authors developed a model that provides the basis for job descriptions, performance appraisals, peer review, and quality management activities. PMID- 1408650 TI - The psychiatric treatment plan. AB - How the treatment planning process is developed and documented in clinical settings is often influenced by various accreditation processes. As healthcare organizations attempt to incorporate written findings and verbal recommendations of surveyors, an incremental approach to the treatment plan often results. The authors describe how they attempted to alleviate this problem by devising a conceptual framework for the treatment planning process using current HCFA and JCAHO standards and data obtained by reviewing treatment plans from almost 100 psychiatric hospitals. PMID- 1408649 TI - A call for action, the challenge of collaboration. PMID- 1408651 TI - The psychodynamic perspective: a conversation with Glen O. Gabbard, MD. Interview by Norine J Kerr. AB - After providing a broad overview of Dr. Gabbard's recent book, Psychodynamic Psychiatry in Clinical Practice, the editor talks with him about a variety of topics, including hospital treatment of clients with dissociative disorders, sexual abuse, borderline and narcissistic clients, and the current status of relationships between psychiatrists and psychiatric mental health nurses. PMID- 1408652 TI - Abstracts of the Italian Society of Physiology XIX spring meeting. Firenze, Italy, 15-17 April 1992. PMID- 1408653 TI - Fever responses in newborn lambs. AB - Neonatal lambs failed to respond with an increase in body temperature to i.v. injection of both endotoxin (0.4 microgram/kg), a Gram-negative bacterial pyrogen, and the cell walls of Staphylococcus aureus (1 x 10(9), a Gram-positive bacterial pyrogen. However, the fall in serum iron concentration that normally accompanies injection of both the pyrogens in adults was not attenuated in the neonates. We believe that the central nervous system origin of the fever pathway is suppressed in neonatal lambs. PMID- 1408654 TI - Thiazide-sensitive Na-Cl cotransport mediates NaCl absorption in amphibian distal tubule. AB - To find out the mechanism(s) underlying NaCl absorption in the distal tubule of Necturus, we devised a variant of the split-drop technique. Following injection an oil column, subsequently split by a NaCl solution isotonic to plasma, a double barrelled microelectrode (conventional/selective to Na+ or to Cl- ions) recorded Na+ (alpha Na) or Cl- (alpha Cl) activity and transepithelial potential (Vte). Paired control/low-Na+ solutions yielded reabsorptive half-times (t1/2) of 0.68 +/- 0.11 min and 7.6 +/- 1.8 min respectively; corresponding Vte values were 22.2 +/- 4.0 mV and -7.6 +/- 1.9 mV. t1/2 values of control versus low-Cl- solutions were 0.77 +/- 0.32 min and 6.5 +/- 1.7 min respectively, whereas respective Vte values were not different from one another: -23.8 +/- 4.3 mV versus -18.8 +/- 5.5 mV. Nominally K(+)-free solutions or bumetanide, 10 mumol/l, did not alter t1/2 or Vte, with regard to the paired control. Amiloride, 5 mumol/l or 2 mmol/l, failed to decrease t1/2 or to lower Vte; apparently, the role of a Na+/H+ antiport does not contribute significantly to NaCl absorption. Furosemide, 0.1 mmol/l, reduced t1/2 by 54% with regard to the control state. Determination of t1/2 as a function of increasing hydrochlorothiazide concentrations revealed apical high- and low-affinity sites, estimated at 0.56 mumol/l and 0.115 mmol/l respectively. Taken together these observations indicate that NaCl absorption is predominantly carried out by an electroneutral Na(+)-Cl- cotransport. PMID- 1408655 TI - Ouabain-induced cell swelling in rabbit connecting tubule: evidence for thiazide sensitive Na(+)-Cl- cotransport. AB - Mechanisms of Na+ entry across the luminal membrane of the rabbit connecting tubule (CNT) and cortical collecting duct (CCD) were investigated in vitro by analyzing factors that block the ouabain-induced tubular swelling. In the CNT and CCD, cell swelling caused by 100 microM ouabain added to the bath was completely blocked by luminal Na+ removal, suggesting that the main factor inducing cell swelling is Na+ entry through the luminal membrane. Trichlormethiazide (100 microM) and amiloride (10 microM) inhibited the swelling in CNT when applied in combination to the lumen, but not when given separately. The swelling was also inhibited by Cl- omission from the lumen in the presence of amiloride. By contrast, no effect was noted when furosemide (100 microM), 4-acetamide-4' isothiocyanatostilben-2,2'-disulfonic acid (1 mM) or 5-(N-ethyl-N isopropyl)amiloride (100 microM) was added to the lumen in the presence of amiloride, indicating the absence of any influence of the Na(+)-K(+)-2Cl- cotransporter and the parallel Na+/H+, Cl-/HCO3- exchanger. The cell swelling in the CCD was blocked by luminal addition of amiloride alone with no effect from trichlormethiazide. In CNT, when the ouabain-induced cell swelling was prevented by both diuretics, addition of parathyroid hormone (PTH, 3 nM) to the bath induced cell swelling, suggesting that another Na+ entry pathway is newly generated by PTH. These results demonstrate that ouabain-induced cell swelling depends on Na+ entry across the luminal membrane. In the CNT, the pathways include an amiloride-sensitive Na+ channel, thiazide-sensitive Na(+)-Cl- cotransport and a PTH-stimulated Na+ pathway, whereas the CCD has only the amiloride-sensitive Na+ channel. PMID- 1408656 TI - Identification of sodium-dependent and sodium-independent dicarboxylate transport systems in rat liver basolateral membrane vesicles. AB - The mechanisms involved in the hepatocellular uptake of Krebs-cycle intermediates were investigated in isolated basolateral (sinusoidal and lateral) rat liver plasma membrane (blLPM) vesicles. An inwardly directed Na+ gradient markedly stimulated uptake of 2-oxoglutarate and succinate into voltage- and pH-clamped blLPM vesicles. This Na(+)-dependent portion of the dicarboxylate uptake was characterized by (a) saturability with increasing substrate concentrations (Km = 6.4-10 mM; Vmax approximately 0.2 nmol min-1 mg protein-1), (b) cis-inhibition by lithium (10 mM), other Krebs-cycle dicarboxylates (1 mM) and DIDS (4,4' diisothiocyanostilbene-2,2'-disulfonic acid; 1 mM) but not by sulphate, monocarboxylates, oxalate, acidic amino acids, bile salts and probenecid, (c) stimulation by an intravesicular negative K(+)-diffusion potential indicating electrogenic [(Na+)n greater than 2-succinate] cotransport, and (d) a pH optimum for transport between 7.0 and 7.5. In the absence of Na+, an inside alkaline pH gradient also markedly stimulated 2-oxoglutarate uptake. This pH-gradient-driven 2-oxoglutarate uptake was insensitive to lithium, but could also be inhibited by DIDS and succinate. Furthermore, saturation kinetics demonstrated Km (approximately 34 mM) and Vmax (approximately 0.8 nmol min-1 mg protein-1) values that were clearly different from those of the Na(+)-dependent uptake system. These results indicate the occurrence of two separate dicarboxylate transport systems along the sinusoidal border of hepatocytes, one being a Na(+) dicarboxylate symporter and the other representing an anion-exchange system. PMID- 1408657 TI - Regional capillary perfusion in muscles with limited blood supply: effects of torbafylline. AB - Severe limitation of blood supply mainly affects the oxidative regions of skeletal muscles. In mammals, they are located medially and are thus not accessible to direct observation. We therefore investigated capillary perfusion in rat tibialis anterior, which has a predominantly glycolytic cortex and oxidative core, using timed intraarterial injection of the fluorochrome thioflavine S conjugated with serum albumin. Muscles with intact blood supply were compared with those in which the blood supply had been limited for 5 weeks by unilateral ligation of the common iliac artery. The effect of a new xanthine derivative, torbafylline (1% solution, 12.5 mg/kg, in two daily doses by gavage, 7 days/week), was also studied. The capillary/fibre ratio was estimated for perfused capillaries (those filled with fluorochrome within 7.5 s after injection; Cp) and all capillaries (those subsequently stained for alkaline phosphatase; Ct), from micrographs of cryostat sections. Regional differentiation in relative capillary perfusion was evident in all muscles samples. Cp:Ct was 0.406 +/- 0.086 (mean +/- 95% CI) in the glycolytic cortex of the contralateral normal muscle, and 0.255 +/- 0.071 in the oxidative core. Muscles with limited blood supply had a significantly lower proportion of perfused capillaries, 0.119 +/- 0.056 in glycolytic and 0.034 +/- 0.038 in oxidative regions. Torbafylline treatment nearly doubled perfusion in the glycolytic regions (Cp:Ct = 0.216 +/- 0.137) and nearly quadrupled it in oxidative (Cp:Ct = 0.121 +/- 0.151) regions of ischaemic muscles. It also improved perfusion in the contralateral muscles (Cp:Ct = 0.705 +/- 0.085 in the glycolytic cortex and 0.583 +/- 0.230 in the oxidative core).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408658 TI - The effects of caffeine and Ca2+ on rigor tension in triton-treated rat ventricular trabeculae. AB - Ventricular trabeculae from rat heart were chemically skinned with Triton-X 100, which disrupts all cellular membranes including the sarcoplasmic reticulum. Trabeculae developed a maintained rigor contracture when adenosine triphosphate was withdrawn from the bathing medium. In all preparations, the final level of rigor force developed in the presence of caffeine (10-40 mM) was greater than under control conditions. However, caffeine failed to increase rigor tension when applied after contracture had fully developed. The effect of caffeine on rigor was maximal at about 15 mM; concentrations greater or less than 15 mM were less effective. On average, caffeine decreased the time required to develop half maximum rigor force. The caffeine-induced potentiation of rigor force occurred in the effective absence of Ca2+ (10(-9) M), in solutions strongly Ca(2+)-buffered with [ethylenebis(oxonitrilo)]tetraaceticacid (10-50 mM). In all preparations, rigor force was found to be independent of [Ca2+] over the range 10(-10) M to about 10(-7) M. These results suggest that caffeine affects rigor force by a direct effect on the myofilaments via a mechanism that is independent of Ca2+. PMID- 1408659 TI - The time course of thyroid-hormone-induced changes in the isotonic and isometric properties of rat soleus muscle. AB - Rat thyroidectomy resulted in changes in a number of parameters used to characterise the mechanical and histochemical status of skeletal muscle. Thus thyroidectomy resulted in a prolongation of soleus slow-twitch muscle isometric contraction time and half-relaxation time with a reduced maximum velocity of shortening and maximum rate of development of tetanic tension but no significant change in twitch: tetanus ratio i.e. the ratio of twitch force/unit area to tetanic force/unit area. In addition the percentage of IIA fibres was reduced and the percentage of type I fibres increased. Triiodothyronine, administered to hypothyroid rats, brought about a speeding of these parameters again with no change in twitch: tetanus ratio. There was an increase in the percentage of IIA fibres with a concomitant reduction in the percentage of type I fibres. These changes were induced over 18 days and resulted in isotonic and isometric properties almost identical to those of soleus muscles from chronically hyperthyroid rats; speeding could be detected as early as 2 days after triiodothyronine had been given. Consideration is given to the possibility that changes in myosin isoforms and/or the kinetics of changes in intracellular calcium concentration in activation and relaxation could account for the time course of the observed changes. PMID- 1408660 TI - Simultaneous measurement of intracellular and extracellular carbonic anhydrase activity in intact muscle fibres. AB - The presence and properties of membrane-bound carbonic anhydrases have been difficult to establish with conventional enzymological and immunohistochemical techniques. We have therefore studied carbonic anhydrase (CA) activity in single intact crayfish muscle fibres by superfusing them alternately with a 4-(2 hydroxyethyl)-1-piperazine-ethanesulphonic acid (HEPES)-buffered and a 5% CO2/HCO3(-)-buffered solution (pH of both solutions 7.4) while recording the intracellular pH (pHi) and extracellular surface pH (pHs) with H(+)-selective microelectrodes. In order to prevent regulation of pHi, Na+ ions were replaced with N-methyl-D-glucamine. Application of the CO2-containing solution produced a fast fall in pHi coupled with a marked (0.5-0.8 pH units) transient increase in pHs. Submicromolar concentrations of acetazolamide (AA) and benzolamide (BA) immediately blocked the pHs transients. A concentration of 8 x 10(-8) M (both compounds) reduced the response by 50%. A more prolonged application of BA and AA at concentrations of 10(-7) M and higher slowed the CO2-induced fall in pHi, which attained a rate corresponding to uncatalysed intracellular CO2 hydration at an AA concentration of 10(-4) M. The effect of BA and AA on the pHi changes developed with a time constant of 25 +/- 4 min and 7.6 +/- 1.5 min respectively, indicating that BA is less permeant than AA. CNO- ions (5 x 10(-4) M) had little effect on the CO2-induced pHs and pHi changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408661 TI - Basal conductance of frog olfactory cilia. AB - The conductance of isolated frog olfactory cilia in the absence of odorants and second messengers has been measured. Current flowing through the pipette-membrane seal rather than the ciliary membrane was subtracted. In normal physiological solutions, each cilium has a conductance averaging 92 pS at the neuronal resting potential. This basal conductance allows current to be carried by K+ or Na+ but not by Cl-. In some cases, single channels with a unit conductance of 153 pS were observed. The conductance of the ciliary membrane implies a length constant for electrotonic conduction of about 160 microns. Since the reversal potential of the basal conductance is near the neuronal resting potential, it should help to stabilize the ciliary potential at some cost to stimulus transduction efficiency. PMID- 1408662 TI - Ion conductances of isolated cortical collecting duct cells. AB - The study of ion conductances in the intact cortical collecting duct (CCD) with the patch-clamp method is rather difficult. An optimized method to isolate CCD cells from rat kidneys using an in vivo followed by an in vitro enzyme digestion is described. Individual CCD segments were collected after this digestion and incubated in EGTA-buffered medium. This procedure resulted in single cells or cell clusters. These freshly isolated CCD cells were studied with different modifications of the patch-clamp method. Membrane voltages measured in the cell attached-nystatin configuration were -74 +/- 1 mV (n = 13) and -68 +/- 3 mV (n = 22) in cells isolated from normal and mineralocorticoid-treated rats respectively. These values and those measured with the nystatin-perforated slow whole-cell configuration (-79 +/- 1 mV, n = 23) are comparable to those measured in principal cells of isolated CCD segments. The cells hyperpolarized after the addition of amiloride and depolarized with the addition of adiuretin to the bath. The amiloride effect was enhanced when cells were isolated from deoxycorticosterone-acetate-treated rats. The cells were strongly depolarized upon elevation of the extracellular K(+)-concentration and did not demonstrate a measurable Cl- conductance. A large-conductance K+ channel (174 pS, n = 5, cell attached, 145 mmol/l K+ in the pipette; 140 pS, n = 12, cell-free, 3.6 mmol/l K+ in the bath) was seen. It had a very low activity on the cell, but a high open probability when excised into a solution with 1 mmol/l Ca2+ on the cytosolic side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408663 TI - Reduction of myocardial cross-bridge turnover rate in presence of EMD 53998, a novel Ca(2+)-sensitizing agent. AB - We have studied the effect of EMD 53998 (5-(1-(3,4-dimethoxybenzoyl)-1,2,3,4 tetrahydrochinolin-6-yl)-6-me thyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one) on cross-bridge turnover rate at varying Ca2+ concentrations. Cross-bridge cycling rate was estimated both by adenosine triphosphatase measurements and determination of mechanical characteristics of constantly activated fibres, which is assumed to reflect cross-bridge kinetics. The results indicate that the turnover rate of myocardial cross-bridges was reduced in the presence of EMD 53998 at low Ca2+ concentrations (pCa greater than or equal to 6.25), but not at higher Ca2+ concentrations (pCa less than or equal to 5.85). PMID- 1408664 TI - Extracellular magnesium regulates intracellular free Mg2+ in vascular smooth muscle cells. AB - Regulatory effects of extracellular magnesium ions ([Mg2+]o) on intracellular free ionized magnesium ([Mg2+]i) were examined in cultured vascular smooth muscle cells (VSMCs) from rat aorta by digital imaging microscopy using the Mg2+ fluorescent probe, Mag-fura-2. With normal Mg2+ (1.2 mM)-containing incubation media, [Mg2+]i in VSMCs was 0.63 +/- 0.09 mM. The ratio of [Mg2+]i/[Mg2+]o was 0.52 +/- 0.07. Elevation of [Mg2+]o up to 4.8 mM induced consistent increments in [Mg2+]i (to a mean values of 1.63 +/- 0.08 mM) in 5 min and lowered the ratio of [Mg2+]i/[Mg2+]o to 0.34 +/- 0.02. Our data suggest that [Mg2+]o can regulate [Mg2+]i, which may be related to its effects on intracellular Ca2+ ([Ca2+]i) and tone of VSMCs. PMID- 1408665 TI - A perfused-cuvette method for fluorimetric studies of non-adherent cells. AB - We have developed a system for immobilizing non-adherent cells for use in macroscopic fluorescence measurements in a perfused cuvette. Using normal human T lymphocytes loaded with the fluorescent Ca(2+)-indicator, fluo-3, we have validated the properties of these cells immobilized on clear, non-fluorescent fluorohalocarbon film (Aclar) using the non-charged cell adhesive, Cell-Tak. PMID- 1408666 TI - Vasopressin V1-antagonist increases the hydroosmotic response to arginine vasopressin in frog urinary bladder. AB - V1-antagonist, [Mca1, D-Phe2, Sar7] arginine vasopressin, at a concentration 0.5 nM to 5 nM increased hydroosmotic effect of 5 nM arginine vasopressin in frog urinary bladder. 1 nM V1-antagonist [Mca1, O-Me-Tyr2] arginine vasopressin does not changed hydroosmotic effect of 0.1 nM dibutyryl cAMP. We suggest that-both V1 and V2-receptors are present on epithelial cells of frog urinary bladder and that V1-receptors are involved in the modulation of the hydroosmotic effect of arginine vasopressin-mediated by V2-receptors. by V2-receptors. PMID- 1408667 TI - A new model of plastic ankle foot orthosis (FAFO (II)) against spastic foot and genu recurvatum. AB - A plastic ankle foot orthosis (AFO) was developed, referred to as functional ankle foot orthosis Type 2 (FAFO (II)), which can deal with genu recurvatum and the severe spastic foot in walking. Clinical trials were successful for all varus and drop feet, and for most cases of genu recurvatum. Electromyogram studies showed that the FAFO (II) reduced the spasticity of gastrocnemius and hamstring muscles and activated the quadricep muscles. Gait analysis revealed a reduction of the knee angles in the stance phase on the affected side when using the FAFO (II). Mechanical stress tests showed excellent durability of the orthosis and demonstrated its effectiveness for controlling spasticity in comparison with other types of plastic AFOs. PMID- 1408669 TI - A Swedish knee-cage for stabilizing short below-knee stumps. AB - Stump length is an important factor in attaining successful prosthetic rehabilitation in below-knee (BK) amputees. Stability of the stump-prosthesis complex is impaired in the case of a stump shorter than 10 cm. Thus, fitting a prosthesis to a BK amputee with a stump which is very short often requires the use of different prosthetic techniques. In this work, the authors suggest the use of a Swedish knee-cage attached to a conventional patellar-tendon-bearing prosthesis as an alternative solution in the case of a short BK stump. Objective evaluation was performed by an analysis of gait and the foot-ground reaction forces. The results obtained indicate an improvement in all the measured parameters resulting from the modified stump-prosthesis complex. PMID- 1408668 TI - Patellar band for patellofemoral disorders: results and indications. AB - In patellofemoral disorders, some cases respond well to conservative management thus the authors' initial treatment is conservative. The Patellar Band (PB) was reported previously (Nakamura et al., 1987). Since then the indications for the band have been investigated. Sixty four patients treated by the PB without operative treatment were classified into eight groups. The Severity of Dysfunction (SOD) was assessed by three grades. The First Grade is dull pain after walking or running for a long distance, the Second Grade is sharp pain on climbing up and down stairs, the Third Grade is a feeling of insecurity. The grouping was as follows: Group Ia - plica syndrome with first Grade of SOD and Ib with Second Grade of SOD. Group IIa - chondromalacia with First Grade of SOD and IIb with Second Grade of SOD. Group III - maltracking patella with patellar pain on flexion. Group IVa - subluxation or dislocation of patella with no previous history of patellar symptom and IVb - recurrent dislocation. Group V - degenerative change of the patella. The PB has been proved to be most effective in Groups Ia, IIa and IVb although it is beneficial in half the cases in Groups IIb and III. The subluxation of the patella was partially reduced without recurrence of dislocation during sports activity and the feeling of insecurity was relieved by the PB. The overall results were not related to age or activity level of the patient. The indication of the band for painful knees was not clearly determined in this study. In all operated cases, it was effective for postoperative instability after lateral release of the retinaculum. PMID- 1408670 TI - Mathematical modelling and field trials of an inexpensive endoskeletal above-knee prosthesis. AB - The swing-phase motion of the shank of an above-knee prosthesis has been modelled mathematically. An inexpensive endoskeletal prosthesis was designed using the Jaipur foot and conduit pipes with a hinge joint for the knee. Results of field trials and the modelling indicate that a very simple above-knee prosthesis can give near normal gait at "normal" walking speeds on flat surfaces. The swing of the shank is most sensitive to the timing of toe-off. PMID- 1408671 TI - Rehabilitation after amputation for vascular disease: a follow-up study. AB - Rehabilitation of one hundred and twenty eight patients with lower limb amputation performed for vascular disease from 1979 to 1987 was assessed. Arteriosclerotic occlusive disease was the most frequent cause of amputation (85.9%). Sixty seven patients (52.3%) were diabetic. Early and late results were analysed. For long-term follow-up evaluation, Univariate method of Kaplan-Meyer product limit was employed. Multifactorial analysis was used to assess factors influencing mortality. On immediate evaluation of rehabilitation with a prosthesis 85.2% of patients were successfully fitted. On long term evaluation 47.8% of below-knee and 22.1% of above-knee amputees were alive and using the prosthesis full time at five years of follow-up (p = 0.0026). Opposite limb preservation at five years was 69.5% for diabetics and 90.2% for non-diabetics, respectively (p = 0.0013). Survival rate at five years was 42.4% for diabetics, and 85.0% for non-diabetics (p = 0.0002). On multifactorial analysis diabetic patients showed a risk of late mortality six times greater than non-diabetics. In conclusion rehabilitation after vascular amputation is feasible in a large number of patients, despite a limited life span. Diabetes represents a major risk factor both for life and for the opposite limb. Knee preservation is an important factor for better rehabilitation. PMID- 1408672 TI - Cause of death of lower limb amputees. AB - A study was carried out on the cause of death of 100 lower limb amputees who had been admitted to the Dundee Limb Fitting Centre, Tayside, Scotland for prosthetic management or wheelchair training. A comprehensive database has been established in the Centre for 25 years and the database is updated regularly. The date of death was collected and recorded. One hundred sequential deaths were investigated to review the cause of their death and compare this with the recorded causes of death for the Tayside population for the year of study. Ninety three per cent had an amputation for vascular related causes, with 73% having a below-knee amputation and 17% above-knee. Heart disease was the most frequent recorded cause of death (51%) of the amputee whereas only 28.1% of the Tayside group died from this pathology (p less than 0.01). Carcinomatosis was reported as a cause of death in 14% of the amputees and 23.5% of the Tayside group. Cerebrovascular disease caused death in 6% of the amputees and in 12.3% of the Tayside group (both p less than 0.01). These findings confirm earlier suggestions that vascular amputees die from heart disease more often than the general population. PMID- 1408673 TI - Revision of amputation stumps in Dodoma--Tanzania. AB - The records of Dodoma Orthopaedic Department, Tanzania were reviewed for the period July 1986 to December 1990 in order to identify the reasons for revision surgery. A total of 26 patients required revision surgery. Two main groups were identified. In the first group 4 patients had a higher level of amputation because of gangrene. In the second group 22 patients had revision surgery because of other stump defects caused by technical mistakes when carrying out the original amputation, or other complications. PMID- 1408674 TI - The geriatric prosthesis as metaphor: a clinical note. AB - This clinical note describes a 96-year-old patient who wears a lengthening prosthesis in connection with the shortening of his leg which occurred after osteomyelitis of his left knee at the age of six years. The prosthesis was made and issued to him when he was twelve years old, and had never been replaced. The considerations that need to be made when replacing the prosthesis of an elderly patient are discussed. In the case described, the prosthesis is replaced by a model that has no fundamental changes from the original. The better fit improves walking considerably and the patient is able to move about safely again using a walking frame. PMID- 1408675 TI - Swimming devices for below-knee amputees. PMID- 1408676 TI - The Knud Jansen Lecture. Education: an investment in everyone's future. PMID- 1408677 TI - History of prostheses and orthoses in Japan. AB - Until the first contact with European civilization in 1543, prostheses and orthoses were not seen in Japanese medical history. Some physicians and surgeons who studied medicine in the Dutch language understood about prostheses and orthoses before the opening of the country in 1868. From 1868 to the end of World War II (1945), prostheses and orthoses were influenced by German orthopaedic surgery. From the latter half of the 1960s the research and development of these have been advanced, because of the establishment of a domestic rehabilitation system, international cultural exchange and economic development. PMID- 1408678 TI - [Intraarterial urokinase infusion therapy with superselective catheterization for acute occlusive cerebrovascular disease]. AB - Intraarterial urokinase infusion therapy with superselective catheterization was performed on 11 patients for acute occlusive cerebrovascular disease. The subjects were five men and six women with a mean age of 70 years (range, 48-83 years). Nine of 11 patients had middle cerebral artery occlusion and two had basilar artery occlusion. The interval from onset to infusion ranged from 3.5 to 9 hours, and the total dosage of urokinase from 24 x 10(4) to 150 x 10(4) IU. Recanalization of the occluded artery was achieved in nine patients (82%), and favorable clinical outcome was achieved in seven patients (64%). Six of whom were discharged with no neurologic deficits. Hemorrhagic infarction occurred in two patients without clinical deterioration. Our observations suggest that intraarterial urokinase infusion therapy with superselective catheterization may be very useful in the acute stage of occlusive cerebrovascular disease. PMID- 1408679 TI - [Echocardiography-guided transseptal left atrial puncture: a safe approach to percutaneous transvenous mitral commissurotomy]. AB - Transseptal left atrial puncture has generally been carried out under fluoroscopic control. In our experience, cardiac tamponade occurred in 3 of 83 cases during transseptal puncture for percutaneous transvenous mitral commissurotomy (PTMC) and percutaneous transvenous aortic valvuloplasty (PTAV). We tried to perform the puncture under simultaneous fluoroscopic and 2DE guidance to decrease the rate of complications. As a result, no complication has occurred in 55 cases. Furthermore, 2DE indicated that directing the puncture needle towards 4 or 5 o'clock was inappropriate, but that 3 o'clock was an appropriate direction for puncture of the fossa ovalis of a left atrium dilated because of mitral stenosis. In conclusion, transseptal left atrial puncture can safely and easily be carried out under a combination of fluoroscopic and 2DE guidance, as this procedure displays the correct position and direction of the needle tip for interatrial septal puncture. PMID- 1408680 TI - [A study of irradiated spines in radiotherapy--using 99mTc-HMDP bone scintigraphy & MR imaging]. AB - When radiation therapy is performed on a patient with malignant tumor, vertebral spines are sometimes included in the irradiation field. In the present study, 99mTc-HMDP uptake was examined in 102 cases of malignant tumors treated with radiation therapy (irradiated total doses from 10 to 70 Gy) in order to clarify the time course of accumulation. The scintigram on the film was transformed with a film digitizer into objective data, and the Accumulation Decreasing Index (ADI) was calculated each month after irradiation. In the group receiving less than 30 Gy, recovery of 99mTc-HMDP accumulation was seen after a mild decrease in the ADI. However, in the group that received more than 40 Gy, no recovery of accumulation was seen, and a large decrease in the ADI followed. Vertebral MRI was performed with and without Gd-DTPA enhancement to calculate the vertebral Signal Intensity Ratio (SIR), and decreased blood flow in the irradiated bone marrow was estimated from the changes in SIR values. In the irradiated area, no definite abnormal accumulation of 99mTc-HMDP was observed against the new metastatic bone tumor. In such cases, MRI should be performed soon after bone scintigraphy in order to detect the tumor. PMID- 1408681 TI - [Fluid-fluid levels in bone and soft tissue tumors demonstrated by MR imaging]. AB - Fluid-fluid levels in bone tumors have been described in aneurysmal bone cysts and other cystic tumors of bones and soft tissue tumors. We experienced three bone tumors (simple bone cyst, bone metastasis, and osteosarcoma) and three soft tissue tumors (fibrosarcoma, two cases of cavernous hemangioma) that showed fluid fluid levels on MR, and investigated their cause. Causes included blood in the cystic spaces, hemorrhage in the tumor, the telangiectatic component of the osteosarcoma, and the cavernous component of the hemangioma. No specific diagnosis could be made based on the finding of fluid-fluid levels. We conclude that fluid-fluid levels on MR are rather nonspecific findings in bone and soft tissue tumors and that the diagnosis should be made on the basis of other radiological and clinical findings. PMID- 1408682 TI - Limited remodelling of expansile Ewing sarcoma after treatment. AB - Radiological findings of Ewing sarcoma have been well documented, and bone expansion or cystic change is known to be a relatively uncommon finding. On the other hand, expected changes in Ewing sarcoma after treatment have also been reported, e.g. regression of extraosseous soft tissue mass, regression and organization of the periosteal reaction, and remodelling of the lytic or sclerotic bone changes. However, remodelling of bone is often limited or incomplete. We saw an atypical change in Ewing sarcoma after treatment due to lack of significant remodelling of the expanding bone. Because such changes might be a cause of misdiagnosis, knowledge of it will help the radiologist in the follow up evaluation. PMID- 1408683 TI - [Computed tomographic evaluation of advanced gastric cancer]. AB - Pre-operative CT of 75 gastric cancer lesions in 74 patients were evaluated for CT diagnosis of N-factor, n-factor and pancreatic invasion. 1. Sensitivity of CT diagnosis of N-factor was depended upon the size of the lymph node; Group A, where all nodular density within the fat plane of anatomical lymph node location were called abnormal, revealed 73.8% sensitivity. Sensitivity of group B was 69.8%, group C was 60.4% and group D was 28.6%. Pre-education of operators did not significantly affect the sensitivity. 2. CT detected No. 3, 7, 8, 9, 12, 14, and 16 in higher sensitivity, and No. 2, 4, 5 and 15 in lower sensitivity as N factor. 3. Overall CT sensitivity of n-factor diagnosis was 48.5% and specificity was 95.6% and accuracy was 88.5%. No. 3, 7 and 8 showed higher sensitivity and specificity, but low sensitivity and specificity were noted at No. 1 and 4. 4. Pancreatic invasion was evaluated objectively from ROC, and sensitivity was 80.0% and 73.3% with and without operative findings, respectively. PMID- 1408684 TI - [MR imaging of thymoma--comparison with CT, operative, and pathological findings]. AB - Twenty-six patients with thymoma, who had magnetic resonance (MR) imaging and computed tomography (CT) before surgery, were studied. Twenty-six thymomas were classified into 11 non-invasive thymomas (Masaoka's clinical stage I) and 15 invasive thymomas (stage II, III, and IV). On MR imaging compared with histological findings, low signal intensity rim of the tumor was corresponded to fibrous capsule of the tumor, and linear and/or reticular low signal intensity lines in the tumor were corresponded to the fibrous septae dividing thymoma into lobules. The detectability of these findings by MR imaging was superior to that by CT. Margin of the tumor was smooth in non-invasive thymoma rather than invasive thymoma. The diagnostic accuracy of invasion to vessel, and pleura or lung on MR imaging and CT was compared with operative and histological findings. MR imaging was same as CT in its ability to detect tumoral invasion to vessel, and slightly superior to pleura or lung. In conclusion MR images clearly show the findings corresponding to pathologic specimens, and MR imaging combining with CT is useful to differentiate non-invasive thymoma to invasive thymoma. PMID- 1408685 TI - [Effects of contrast media under systemic heparinization on blood coagulation and fibrinolytic system during angiocardiography--comparison of ionic and nonionic contrast media]. AB - Nonionic contrast media are suggested to cause increased thromboembolism (in vivo), because of less inhibitory action on blood coagulation and platelet aggregation (in vitro) as compared with ionic contrast media. Therefore, to prevent thrombotic complication, we examined whether differences in blood coagulation and fibrinolytic system between the two groups received nonionic (iopamidol) and ionic (ioxaglate) contrast media are seen in vivo when 2,500 unit heparin is administered during angiocardiography. 20 patients undergoing routine angiocardiography were randomized to two groups of 10 patients each. Blood heparin concentration, activated partial thromboplastin time, prothrombin time, thrombin-antithrombin III complex (TAT), antithrombin III, fibrinogen, alpha 2 plasmin inhibitor plasmin complex, fibrinogen and fibrin degradation product were measured at four stages during the procedure: before and 5 min after 2,500 unit bolus heparin administration, 5 min after left ventriculography, and at the end of procedure. Systemic heparinization inhibited clot formation in the presence of nonionic contrast media. TAT generations were elevated before heparinization, after heparinization, however these generations were remarkably inhibited in both groups. No remarkable differences were noted at 40 +/- 14 min duration of procedure when these parameters were compared between the two groups. Since nonionic contrast media did not activate blood coagulation and fibrinolytic system with 2,500 unit heparin administration as compared with ionic contrast media, systemic heparinization was demonstrated to be effective in the prevention of thrombotic complication. PMID- 1408686 TI - [An experimental study on MR lymphography with various iron colloid agents]. AB - Magnetic resonance (MR) lymphography with iron colloid agents was evaluated in an animal model. The agents examined were ferric gluconate (FeG), saccharated ferric oxide (SFO), iron chondroitin sulfate (ICS) and cideferron (CiF), which were used as intravenous medication for iron deficiency anemia. The author performed time dose-response and correlative histologic studies. MR images of the popliteal lymph nodes of rabbits were obtained at 1.5 T with a spin-echo sequence (TR = 300, TE = 30 msec) before and after subcutaneous injection of the agents to dorsal hind-feet. The images were evaluated by signal intensity (SI). Histologic specimens were evaluated for distribution and relative quantity of stained iron with a color image analyzer. The SI with FeG 4 mgFe increased by 50% at 5 to 60 minutes after injection but returned to the pre-contrast level 48 hours after. The SIs with SFO 8 mgFe, ICS 1 mgFe and CiF 1 mgFe decreased to the background level at 60 minutes and 48 hours after. The histologic study in combination with the images indicated that in case of FeG the particles in lymph increased SI while in the other agents those within macrophages decreased SI. PMID- 1408688 TI - Digital imaging of dose distributions using NMR imager. PMID- 1408687 TI - [Histopathological study of the esophageal injury induced by high-dose-rate intracavitary irradiation. Experimental study on the rabbits]. AB - Despite the effectiveness of the intracavitary irradiation as the boost therapy for the esophageal cancer, the side effect of the normal part of the esophagus has not been studied enough. The purpose of this study is to investigate the histopathological responses of the rabbit esophagus to the high-dose-rate intracavitary irradiation. Esophageal ulcer was observed in the specimen received a dose of 15 Gy during 7 to 28 days after irradiation. Before the mucosal changes were observed, edema and cell infiltration were found in lamina propria. Chronic injury such as necrosis and degeneration of epithelium, and degeneration of the wall of blood vessels was seen at 6 months. No marked changes were found in the specimen received doses of 5 and 10 Gy. The influences of administration of mucosal protection agent and cancer chemotherapeutic drug were also studied. Administration of mucosal protection agent protected the occurrence of severe ulcer and accelerated the recovery from mucosal damage. Administration of cancer chemotherapeutic agent enhanced the radiation injury by the intracavitary irradiation of the esophagus. In conclusion, it was strongly suggested that a single dose of the high-dose-rate intracavitary irradiation should be reduced less than 10 Gy to prevent the esophagus from severe injury. PMID- 1408689 TI - [A survey of annual radiation dose for radiation workers from occupational and medical exposures in Kyushu]. AB - This study was carried out to determine annual dose equivalents of exposure in workers exposed to medical radiation and occupational radiation in an enterprise associated with nuclear power plants. The results indicated that medical exposure is much higher than occupational exposure. Average annual effective dose equivalents for medical and occupational exposure were 4.0-7.5 mSv and 2.4-3.6 mSv, respectively. Individual occupational exposure limits have been well controlled and maintained at one-fifth of the dose limit for radiation workers (50 mSv/yr). On the other hand, medical exposure in the older workers of this enterprise has been increasing as a result of X-ray diagnosis with barium meal. PMID- 1408690 TI - [Transjugular intrahepatic portosystemic stent shunt (TIPSS)]. AB - Our first clinical experience of TIPSS made for a 52-year-old patient with recurrent life threatening variceal bleeding is described. Although shunt-making between the right hepatic vein and the right portal vein and placement of Gianturco-Rosch Z stents were successfully made without significant complication related to the procedure, sufficient decompression of the portal vein pressure was not obtained because of compression on these stents at the tortuous portion of the shunting tract. Some technical problems of the procedure are also discussed, especially about choice of metallic stents and puncture technique. PMID- 1408691 TI - [Endoscopic visualization of luminal organ and great vessels with three dimensional CT scanner. A new trial using volumetric CT]. AB - Thirty cases examined by three dimensions CT scanner (3DCT) were reported. The observation of inner view using 3DCT were performed in 12 large vessels with vascular disorder, 10 pulmonary bronchus with lung cancer and 8 common bile ducts involved obstructive disease. In order to visualize interface of the lumen, a new software which was devekioed by HITACHI MEDICO Inc. and us was brought in. In all cases but one the inner view of the luminal organ was clearly demonstrated as 3D images and it was possible to judge some changes of luminal interface involved by the diseases. The 3DCT endoscopic image might be useful as a new endoscopic technique without fiberscopy. PMID- 1408692 TI - New Jersey State Nurses' Association history: what is past is prologue. PMID- 1408694 TI - Perspectives in nursing 1991-1993. PMID- 1408693 TI - Nursing datasource 1992. Volume I. Trends in contemporary nursing education. PMID- 1408695 TI - Distance education: turf and technology. PMID- 1408696 TI - Recent trends in nursing education. PMID- 1408698 TI - A caring community within acute-care institutions? It can be done, and here's how. PMID- 1408699 TI - Violence against women: clinical issues. PMID- 1408697 TI - Case management: within and beyond the walls. AB - Results of this study demonstrated no significant differences in the frequency of the instrumental use of case management skills between nurses who graduated from the NAMFE program (NAMFE group) and those who were about to enter the program (comparison group); however, there was a significant difference (p < .0001 level) in the perceived preparation for performance of these skills between the two groups. Currently, few educational programs provide nurses with the essential knowledge and skills to function in the role of case manager; yet, the job market demands it of them. The program was able to fill the gap between education and service. Although the NAMFE course no longer is available for continuing education credit through the University of Kansas School of Nursing, the course currently is offered as an elective for senior level students and graduate students. Also, the curriculum materials and teaching strategies manuals, developed as part of this grant, and consultations regarding the use of these materials are available. PMID- 1408700 TI - Home care: the direction of future health care services. PMID- 1408702 TI - Presidential address for the biennial convention. PMID- 1408701 TI - Competition in accrediting: letting other voices be heard. PMID- 1408703 TI - Community-based nursing education in El Salvador. PMID- 1408704 TI - Here there be dragons: departing the behaviorist paradigm for state board regulation. PMID- 1408705 TI - Quality education for minorities: myths, realities, and strategies. PMID- 1408706 TI - Nursing and society--the unfinished agenda for the 21st century. PMID- 1408707 TI - Diversity in nursing faculty hinges on diversity in nursing students. AB - In this chapter, I attempted to explicate and highlight some of the interrelationships which exist in higher education between white male and female faculty members from a minority perspective. I discussed the effect of attitudes on the success of minority students and faculty in light of projected demographic changes. I hope that white female faculty members will become more cognizant of how negative attitudes impact upon both their own performance in higher education and also how the inculcation of these attitudes can be transferred to minority faculty members with devastating results. Change is difficult in all spheres of life, but without some modicum of change, life will go on as usual. Minority faculty members and students deserve at the very least a fair chance in the game we call higher education. PMID- 1408708 TI - Educational implications of nursing faculty diversity. PMID- 1408709 TI - Valuing cultural diversity in nursing faculty. PMID- 1408710 TI - Nursing from the international perspective. PMID- 1408711 TI - A community-based health program for the homeless. PMID- 1408712 TI - Nursing and community advocacy: health needs of the young. PMID- 1408713 TI - A church-based program for the homeless. PMID- 1408714 TI - Prevention as the intervention of choice. PMID- 1408715 TI - Distance education: turf and technology. AB - Distance learning fits with the mission and strategic plan of the University of Texas at Arlington. We believe these educational opportunities in nursing are highly desirable. The Board of Nurse Examiners for the State of Texas has approved this project and the Texas Higher Education Coordinating Board has approved it as a pilot project. The school will continue evaluation and creative problem-solving in the use of distance education. PMID- 1408716 TI - Distant learning in nursing. PMID- 1408717 TI - [New winds in the Scandinavian labor market]. PMID- 1408718 TI - [Good experiences with telemedicine in the regional hospital of Tromso]. AB - The University Hospital of Tromso and the Norwegian Telecom Research project "Telemedicine in North Norway" has used video conferences as a tool in making remote diagnosis in the medical areas: Pathology, diagnosis from microscope images; dermatology, endoscopy in otorhinolaryngology, echocardiology and radiology. The project has also developed a communication system between general physicians and the department of the clinical chemistry in which test results are transported electronically from the laboratory to the physicians. Experience to date suggests that the quality of telecommunication in diagnostic services is good and that access to such facilities is beneficial to the users. PMID- 1408719 TI - Epidemiology of childhood diabetes in the Baltic area. AB - Insulin-dependent diabetes mellitus (IDDM) is a chronic disease with unknown aetiology and therefore without effective measures for its prevention. Both genetic and environmental factors play a role in the development of the disease. Comparative studies between different populations of varying genetic and environmental backgrounds are needed for better understanding of the aetiology of IDDM. PMID- 1408720 TI - [Insulin treatment--its physiological principle]. AB - Insulin treatment based on the physiological principle not only results in better glucose homeostasis but also in improved quality of life for the patients. The frequency of metabolic events also seems to be controlled, particularly when the multiple injection system is used. However, a prerequisite is regular, preferably daily, blood sugar monitoring to enable the insulin dosage to be adapted according to food intake and exercise. Advances in our knowledge of the importance of the injection technique used may contribute to the optimisation of insulin treatment and thus of glucose homeostasis. PMID- 1408721 TI - Advances in diabetes research. PMID- 1408722 TI - [Chronic inflammatory bowel disease]. AB - Chronic inflammatory bowel disease (IBD) encompasses the disease entities, ulcerative colitis (UC) and Crohn's disease (CD). An aetiologic agent has not yet been defined and the diagnosis is based, therefore, on the sum of clinical, paraclinical, radiologic, endoscopic and histopathologic features. In recent years pathogenetic studies have focused on immune mechanisms, transmissible infectious agents, the potential role of the normal intestinal flora, dietary factors, enzymatic alterations and genetic features, in addition to vascular, neuromotor, allergic and psychologic factors. The corner stones in medical therapy of IBD are still corticosteroids and sulphasalazine (SAZ). The new oral salicylates, which are analogues of SAZ or "slow release" preparations of 5 aminosalicylic acid (mesalazine), have provided a therapeutic progress, because they are tolerated better than SAZ. Immunosuppressive agents, such as azathioprine and 6-mercaptopurine, reduce the requirement for corticosteroids and are effective in refractory CD, but the effect is delayed up to several months. The therapeutic action of cyclosporine A is not sustained, but often associated with side effects. Metronidazole has a beneficial effect on perineal disease. The efficacy of antimycobacterial drugs, sodium-cromoglycate, lidocaine, clonidine and sucralfate has been reported only in optimistic case stories and small open trials. A diet, rich in omega-3-fatty acids, modifies leukotriene (LT) production, but its clinical efficacy is insufficient. The first anti-leukotriene drug, zileuton, has recently been evaluated and a significant, although insufficient, clinical response was obtained by a 70 per cent inhibition of rectal LTB4 synthesis. Dietary therapy may be useful as an adjunct to treatment of local complications in CD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408723 TI - [Life style patterns in patients with chronic disease]. PMID- 1408724 TI - [Which factors cause type-1 diabetes?]. AB - Type 1 diabetes is due to selective and irreversible destruction of pancreatic beta-cells via an autoimmune process. The pathogenetic course is dependent both upon genetic predisposition for the disease and upon one or more environmental factors--eg, viral infection, dietary factors, and exposure to toxins or mental stress. PMID- 1408725 TI - [Can type-1 diabetes in children be prevented?]. AB - Increased knowledge of the etiopathogenesis of Type 1 diabetes has focused great interest on the possibilities of preventing the disease. Type 1 diabetes is considered to be a chronic autoimmune disease characterized by gradual beta-cell destruction mediated by autoreactive T-lymphocytes during an asymptomatic prediabetic phase of varying duration. Both experimental and epidemiologic data indicate that nutritional cow milk exposure early in life may play a critical role in the initiation of beta-cell destruction. Accordingly a primary prevention study has been planned to test the hypothesis that dietary elimination of cow milk proteins over the first 9 months of life will decrease the subsequent risk of childhood type 1 diabetes in high risk infants. The possibility of identifying prediabetic individuals before decisive loss of beta-cell function by various islet cell-specific autoantibodies enables measures of secondary prevention in the prediabetic phase. There are indications from experimental and human studies that nicotinamide, a water-soluble group B vitamin, may be effective in preventing or delaying the presentation of diabetes. A European multicentre study will be initiated in the near future to explore whether oral nicotinamide can prevent or delay the clinical manifestation of Type 1 diabetes in high risk first degree relatives of diabetic children. We have to wait for the results of these intervention studies for years, and similarly other prevention strategies have to be tested in large-scale long-lasting clinical trials. Nevertheless, prevention of childhood diabetes may become a reality in the next century. PMID- 1408726 TI - [Diabetic coma--an unnecessary death]. AB - Diabetic ketoacidosis remains a significant cause of death in cases of insulin dependent diabetes mellitus (IDDM). Among patients hospitalised for diabetic ketoacidosis, the death rate is 5-10 per cent, cardiovascular disease, infection, and ARDS (adult respiratory distress syndrome) being major contributory factors, whereas the degree of acidosis does not differ from that among survivors. Ketoacidosis is a major determinant of the two-fold higher mortality among the youngest age-groups of IDDM patients. The age-specific incidence of ketoacidosis among patients under 20 years of age is several time higher than that among patients over 50. Intensified insulin treatment, using multiple injections or insulin pumps, probably results in an increased risk of insulin deficiency owing to the smaller insulin depots. Thus, there is a need of intensified testing for ketonuria and improved education of patients, physicians and other health care personnel, in order to promote the prevention or rapid, effective treatment of diabetic ketoacidosis. PMID- 1408727 TI - [Diabetic nephropathy]. AB - Diabetic nephropathy is a common complication in diabetes mellitus. In addition to the risk of renal failure, patients with established nephropathy are at increased risk of proliferative retinopathy and cardiovascular disease. As the earliest prodrome of nephropathy is microalbuminuria, albumin excretion needs to be monitored with a reliable method in all diabetics. In the event of microalbuminuria, diabetes treatment needs to be intensified to optimise metabolic regulation. Early institution of antihypertensive treatment is essential to avoid progression to clinical nephropathy. PMID- 1408729 TI - [Scandinavian Central Committee Meeting in Tromso. Physician unemployment and structural changes in delivery of Scandinavian health care]. PMID- 1408728 TI - [Insulin-dependent diabetes mellitus--improved prognosis and insurance outlook]. AB - The marked improvement during recent years in prognosis for patients with insulin dependent diabetes mellitus (IDDM), has also had actuarial consequences. In the article is described the development in prognosis over the past 60 years, based (inter alia) on findings in almost 3,000 IDDM patients with onset during the period, 1933-1972, and referred to the Niels Steensens Hospital in Denmark. PMID- 1408730 TI - [Treatment of advanced anal cancer]. AB - Anal carcinoma affects between 30 and 40 Norwegians every year. The disease is twice as frequent in women as in men. It is usually located in the anal canal only, and is cured by a combination treatment with chemotherapy and radiotherapy. Metastatic anal carcinoma has a poor prognosis. We present two such cases. 5 fluorouracil in combination with cisplatin or mitomycin C can give responses even in advanced cases. Radiotherapy may also be of value. In view of the difference between norwegian clinics in the treatment of anal carcinoma, there would appear to be a need of a Scandinavian or international study based on standardized treatment. PMID- 1408731 TI - [Hospice care in general practice?]. AB - In a primary health care district in southern Sweden, a programme was launched to treat terminally ill cancer patients in their own homes, on the lines of the hospice mode. The quality of life of these patients has been found to be improved, and the cost to the community to be less than that of institutionalised hospital care. Other patient categories that might benefit from this form a care are those with AIDS, severe neurological diseases, or chronic cardiac or respiratory insufficiency. PMID- 1408732 TI - [Lead and health]. AB - Large sums are being invested in the USA at present with a view to reducing the exposure of risk groups to lead. The Centers for Disease Control (Atlanta) have recently issued new limits for lead concentrations in children, the Occupational Safety and Health Administration is preparing to issue new threshold limit values (TLVs) for airborne lead in the USA, and a national laboratory control system is being built up. PMID- 1408733 TI - Questions concerning plasma cell leukaemia. AB - The classical concept of plasma cell leukaemia (PCL) is reviewed. This disease invariably concerns myeloma, either in its terminal phase (secondary PCL) or particularly rapid and aggressive (primary PCL). A more precise definition of primary PCL would be given by the term leukaemic myelomatosis. Characterization of the membrane antigen CD 56, responsible for the cytoadhesion of malignant plasmocytes in the bone marrow, today offers a convincing pathogenic hypothesis to elucidate this affection which would now appear to be no more than a variant form of myeloma. Acute immunoblastic-plasmoblastic leukaemia and mature cell leukaemic lymphoma would seem to be pathologically related to PCL. Finally, the problems posed by the "enigmatic" plasmacytoid monocyte are discussed. PMID- 1408734 TI - Progress and survival factors in acute non lymphocytic leukemia. A 15 year analysis. AB - We analyzed a population of adults with acute non lymphocytic leukemia (ANLL) treated from 1972-1989 to identify prognostic factors and the influence of therapy over time. To 179 patients treated at Sunnybrook Medical Centre (SMC) were added 114 patients from published patient series from Princess Margaret Hospital (PMH) all treated during that period. All PMH and 98 SMC patients received one of three remission induction protocols: CAV (cyclophosphamide, cytosine arabinoside [ara-C], vincristine) 1973-1976 (n = 46); ACT (Adriamycin, ara-C +/- 6-thioguanine) 1976-1983 (n = 83); high dose ara-C and corticosteroids 1983-1987 (n = 83). The remainder either received supportive therapy only or minimally toxic therapy (e.g., low dose ara-C, 6-mercaptopurine) due to presenting complications such as advanced age, severe concurrent medical condition, or most recently at SMC only, mitoxanthrone and ara-C, and were excluded from analysis. Responses obtained at the two institutions were identical, no survival advantage of any particular protocol was seen. Overall median survival was 8.5 months for patients treated on protocol and 20 months for those entering complete remission. Patients treated with supportive or minimally toxic therapy (n = 76) had a median survival of less than two months. In multivariate analysis, the only important factors for survival were complete response to initial therapy; complete response to second induction therapy following either first relapse (n = 89) or lack of complete response to first therapy (n = 15); and normal cytogenetic analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408736 TI - Serum and erythrocyte ferritin in regular blood donors. AB - This study evaluated 217 regular blood donors, with the aim of measuring their iron stores and recording the influence of donation frequency. In the population studied, 10% of men and 15% of women showed reduced iron stores of the erythropoietic marrow (erythrocyte ferritin less than the normal range) and 64% of the population showed a latent deficiency in iron (serum ferritin values less than the reference values). An increase in donation frequency was followed by an important decrease in serum ferritin concentration. Blood haemoglobin levels were inferior to control limits in 4% of men and 15% of women, measurements of haemoglobin being the legal screening test performed at the time of donation. However, this test gives a late indication of an already established iron deficiency and should be replaced by the determination of serum ferritin in order to avoid the possible appearance of iron deficiency. Erythrocyte ferritin is another late indicator of iron depletion and hence is of little interest for the control of blood donors. PMID- 1408735 TI - Monitoring of erythropoiesis by serum transferrin receptor levels in a case of chronic lymphocytic leukaemia and pure red cell aplasia treated with ciclosporin. AB - The authors present the case of a patient with chronic lymphocytic leukaemia complicated by pure red cell aplasia. Successful treatment with ciclosporin was facilitated by assay of serum transferrin receptor, which demonstrated a prompt and sustained response of marrow erythropoiesis to this therapy. PMID- 1408737 TI - A complex pattern of antigen receptor gene rearrangements in a case of Philadelphia positive acute lymphoblastic leukaemia. AB - The paper describes a case of Philadelphia (Ph) positive acute lymphoblastic leukaemia (ALL) presenting with high white cell count and central nervous system involvement. Immunophenotypically the case was characterized as common ALL. The t(9;22) abnormality corresponded to a rearrangement within the breakpoint cluster region gene, while antigen receptor gene studies showed multiple rearrangements of the immunoglobulin heavy chain gene (IGH) concomitant with a single rearrangement of the T cell receptor beta chain gene (TCR beta). We speculate that this case represents the neoplastic transformation of a stem cell, the Ph abnormality being involved in the early steps of transformation. It is conceivable that the IGH but not the TCR beta gene was accessible to recombination within the malignant clone, thus generating the multiple rearrangements observed. If this is the case, these findings would appear to be compatible with the hypothesis that antigen receptor gene rearrangements may be partly dependent on the accessibility of the corresponding genetic loci. PMID- 1408738 TI - Hairy cell leukemia and factor VIII inhibitor: a case report. AB - Acquired factor VIII inhibitors are usually described in hemophilia A, although some cases have been documented in chronic inflammatory diseases and malignant tumors. We report here the first case of a factor VIII inhibitor appearing in the course of hairy cell leukemia. Interferon therapy over a 5 month period led to complete remission of leukemia with parallel disappearance of the acquired factor VIII inhibitor. PMID- 1408739 TI - Tuberculosis associated hemophagocytic syndrome complicated with severe bone marrow failure and disseminated intravascular coagulation. AB - Tuberculosis associated hemophagocytic syndrome (HPS) has recently been recognized as a benign reactive histiocytic proliferation with marrow hemophagocytosis. To our knowledge, only five autopsy documented cases have previously been reported. We present here a unique case of the disorder complicated by severe bone marrow failure and disseminated intravascular coagulation. The possible mechanisms of these complications are discussed and it is concluded that the immunological disturbances usually occurring in miliary tuberculosis could play a role in the pathogenesis of HPS. PMID- 1408740 TI - Long-term survival in remission of adult acute myeloid leukaemia (AML) patients. PMID- 1408741 TI - Identification of Ets-like lymphoid specific elements within the immunoglobulin heavy chain 3' enhancer. AB - Recently we identified an additional enhancer in the 3' end of the immunoglobulin heavy chain (IgH) locus. To identify individual regulatory elements within the rat IgH 3' enhancer, deletion analysis was performed. Transfection experiments using reporter constructs suggest that the enhancer contains three functionally distinct domains, two of which are lymphoid specific and one domain is active in both lymphoid and in nonlymphoid cells. The three domains together contribute to enhancer function and act synergistically. Further analyses suggest that a putative mu E1 site, octanucleotide motif, mu E3 site, and mu B/Ets-like motif are important for the overall transcriptional activity of the IgH 3' enhancer. Moreover, we provide evidence that an additional Ets-like element, micro A, is involved in the tissue specific regulation of enhancer activity and that binding of a protein to this element correlates with the transcriptional activity of one of the lymphoid restricted domains. PMID- 1408742 TI - An abasic site analogue activates a c-Ha-ras gene by a point mutation at modified and adjacent positions. AB - Synthetic c-Ha-ras genes with an analogue of an abasic site in the first or the second position of codon 12, or in the second position of codon 61 were constructed and transfected into NIH3T3 cells. The genes with the lesions in codon 12 exhibited more focus formation than a normal c-Ha-ras gene, while the gene with the lesion in codon 61 did not. Transformed cells were isolated from the foci, and the c-Ha-ras genes present in the transformants were analysed. A point mutation to A in the modified position was found most frequently in the cases of ras genes modified in codon 12. Surprisingly, point mutations in the adjacent position were also detected. These results indicate that dTMP, and not dAMP, was mainly incorporated into the sites opposite to the abasic site analogue, and that incorrect deoxynucleotides were incorporated in the position adjacent to the abasic site analogue. PMID- 1408743 TI - Sequence comparison of new prokaryotic and mitochondrial members of the polypeptide chain release factor family predicts a five-domain model for release factor structure. AB - We have recently reported the cloning and sequencing of the gene for the mitochondrial release factor mRF-1. mRF-1 displays high sequence similarity to the bacterial release factors RF-1 and RF-2. A database search for proteins resembling these three factors revealed high similarities to two amino acid sequences deduced from unassigned genomic reading frames in Escherichia coli and Bacillus subtilis. The amino acid sequence derived from the Bacillus reading frame is 47% identical to E.coli and Salmonella typhimurium RF-2, strongly suggesting that it represents B.subtilis RF-2. Our comparison suggests that the expression of the B.subtilis gene is, like that of the E.coli and S. typhimurium RF-2 genes, autoregulated by a stop codon dependent +1 frameshift. A comparison of prokaryotic and mitochondrial release factor sequences, including the putative B.subtilis RF-2, leads us to propose a five-domain model for release factor structure. Possible functions of the various domains are discussed. PMID- 1408744 TI - Interaction of the erythroid transcription factor cGATA-1 with a critical auto regulatory element. AB - We have performed a mutational analysis of the promoter for the chicken erythroid specific GATA-1 transcription factor, and have investigated in detail the interaction of the factor with an upstream auto-regulatory element (ARE). We find that a single proximal GATA binding site of the ARE is required for promoter activity in primary erythroid cells; however, this minimal promoter is inappropriately active in fibroblasts. At least two molecules of GATA-1 can interact with the ARE, and sequences outside of the consensus site appear critical for the transcriptional activity of the bound protein. Finally, we provide evidence for complex protein/DNA interactions at the ARE, including the ability of GATA-1 to bend DNA. PMID- 1408745 TI - Repair and replication of plasmids with site-specific 8-oxodG and 8-AAFdG residues in normal and repair-deficient human cells. AB - The in vivo mutagenicity of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and N (guanin-8-yl)-N-acetyl-2-aminofluorene (8-AAFdG) in human cells was determined by transfecting various cell lines with plasmids that carried a single adduct at a defined site. 8-OxodG is one of the many DNA modifications formed by oxygen radicals, and was found to be highly miscoding during replication with purified DNA polymerases in vitro. Here we show that the frequency of mutations induced by 8-oxodG during replication in vivo is at most only 2% above background. The most predominant mutation found was a single G----T transversion. The frequency of this transversion was found to be 3 to 5-fold increased in excision repair deficient XP-A cells. Interestingly, also the replication of 8-oxodG containing plasmids was significantly impaired (approximately 4-fold) in the XP-A cells, but not in HeLa cells, normal fibroblasts or XP-A revertant cells. When 8-AAFdG containing plasmids were used, the mutation frequencies did not exceed background levels (less than 2%) with any of the cell lines tested. The presence of 8-AAFdG almost completely inhibited plasmid replication (more than 50-fold) in XP-A cells. Apparently, both 8-AAFdG and 8-oxodG are not or poorly repaired in these cells, causing a block of DNA replication. This suggests that both lesions are substrates for excision repair, although to a varying extent. PMID- 1408746 TI - Gene dosage as a possible major determinant for equal expression levels of genes encoding RNA polymerase subunits in the hypotrichous ciliate Euplotes octocarinatus. AB - Ciliated protozoa harbor two different types of nuclei in each cell. The diploid micronucleus is the transcriptionally inactive generative nucleus, while the macronuclous contains a highly amplified transcriptionally active genome of lower complexity. The macronuclear genes encoding the two largest subunits of both RNA polymerases I and II of Euplotes octocarinatus were identified by a novel method of two step PCR walking, employing primer pairs derived from telomeric sequences of the organism and known conserved RNA polymerase polypeptide sequences, respectively. The relative gene dosage was determined. The genes are present in equal copy numbers for the respective matching subunits. Northern hybridizations showed comparable amounts of transcripts, as well, within the matching pairs. Mapping of the 5'-termini of the transcripts of the gene sized chromosomes showed that the upstream nontranscribed regions are very short and contain characteristic sequence motifs which could be the determinants of equal promoter strengths for subunits of a common RNA polymerase. PMID- 1408747 TI - Stoichiometry of the Cre recombinase bound to the lox recombining site. AB - The site-specific recombinase Cre from bacteriophage P1 binds and carries out recombination at a 34 bp lox site. The lox site consists of two 13 bp inverted repeats, separated by an 8 bp spacer region. Both the palindromic nature of the site and the results of footprinting and band shift experiments suggest that a minimum of two Cre molecules bind to a lox site. We report here experiments that demonstrate the absolute stoichiometry of the Cre-lox complex to be one molecule of Cre bound per inverted repeat, or two molecules per lox site. PMID- 1408748 TI - Antisense probes targeted to an internal domain in U2 snRNP specifically inhibit the second step of pre-mRNA splicing. AB - Functional domains within the mammalian U2 snRNP particle that are required for pre-mRNA splicing have been analysed using antisense oligonucleotides. A comparison of the melting temperatures of duplexes formed between RNA and different types of antisense oligonucleotides has demonstrated that the most stable hybrids are formed with probes made of 2'-O-allyl RNA incorporating the modified base 2-aminoadenine. We have therefore used these 2'-O-allyl probes to target sequences within the central domain of U2 snRNA. Overlapping biotinylated 2'-O-allyloligoribonucleotides complementary to the stem loop Ila region of U2 snRNA (nucleotides 54-72) specifically affinity selected U2 snRNA from HeLa nuclear extracts. These probes inhibited mRNA production in an in vitro splicing assay and caused a concomitant accumulation of splicing intermediates. Little or no inhibition of spliceosome assembly and 5' splice site cleavage was observed for all pre-mRNAs tested, indicating that the oligonucleotides were specifically inhibiting exon ligation. This effect was most striking with a 2'-O allyloligoribonucleotide complementary to U2 snRNA nucleotides 57-68. These results provide evidence for a functional requirement for U2 snRNP in the splicing mechanism occurring after spliceosome assembly. PMID- 1408749 TI - The mechanisms controlling ribosomal protein L1 pre-mRNA splicing are maintained in evolution and rely on conserved intron sequences. AB - Sequences corresponding to the third intron of the X.laevis L1 ribosomal protein gene were isolated from the second copy of the X.laevis gene and from the single copy of X.tropicalis. Sequence comparison revealed that the three introns share an unusual sequence conservation which spans a region of 110 nucleotides. In addition, they have the same suboptimal 5' splice sites. The three introns show similar features upon oocyte microinjection: they have very low splicing efficiency and undergo the same site specific cleavages which lead to the accumulation of truncated molecules. Computer analysis and RNAse digestions have allowed to assign to the conserved region a specific secondary structure. Mutational analysis has shown that this structure is important for conferring the cleavage phenotype to these three introns. Competition experiments show that the cleavage phenotype can be prevented by coinjection of excess amounts of homologous sequences. PMID- 1408750 TI - Characterization and purification of Adh distal promoter factor 2, Adf-2, a cell specific and promoter-specific repressor in Drosophila. AB - Chromatin footprinting in Drosophila tissue culture cells has detected the binding of a non-histone protein at +8 of the distal Adh RNA start site, on a 10 bp direct repeat motif abutting a nucleosome positioned over the inactive Adh distal promoter. Alternatively the active promoter is bound by a transcription initiation complex. We have characterized and purified a protein Adf-2 that binds specifically to this direct repeat motif 5'TCTCAGTGCA3', present at +8 and -202 of the distal RNA start site. DNase I footprinting, methylation interference, and UV-crosslinking analyses showed that both direct repeats interact in vitro with a nuclear protein of approximately 120 kilodaltons (kDa). We purified Adf-2 through multiple rounds of sequence-specific DNA affinity chromatography. Southwestern analysis showed that the purified 120 KDa polypeptide binds the Adf-2 motif efficiently as a monomer or homomultimer. In vivo titrations of Adf-2 activity with the Adf-2 motif by transient co-transfection competitions in different Drosophila cell lines suggested that Adf-2 is a cell-specific repressor. Adf-2 has been detected ubiquitously in vitro, but is functional in vivo as a sequence specific DNA binding protein and repressor only in the cells that have the inactive distal promoter. We discuss the possibility that an activation process is required for Adf-2 protein to bind DNA and function in vivo. PMID- 1408751 TI - Extensive turnover of telomeric DNA at a Plasmodium berghei chromosomal extremity marked by a rare recombinational event. AB - The dynamics of telomere turnover were studied in Plasmodium, whose telomeric structures consist of linear, recognisable sequences of two distinct repeats (TTTAGGG and TTCAGGG). Independent recombinant clones containing a well-defined chromosomal extremity of Plasmodium berghei, both before and after a rare insertion event took place, were obtained from clonal parasite populations and analysed. The insertion, which splits the original telomere and causes a significant reduction in the size of the telomeric structure, is shown to consist of an integer number of subtelomeric repeats typical of P.berghei, flanked on both sides by telomere-derived motifs. Analysis of the telomeric repeat sequence heterogeneity in the otherwise homogeneous populations examined, is compatible with a model in which diversification of a given telomere is driven by the occurrence of breakpoints whose frequency rapidly increases along the telomeric tract when moving in the outward direction. The breakpoints might be due either to terminal deletions followed by random serial addition of the two repeat versions, or to recombination events. The shortening/elongation mechanism is favoured against the recombination hypothesis because of the absence of higher order patterns in the sequence of telomeric repeats. PMID- 1408752 TI - Ligand dependence of estrogen receptor induced changes in chromatin structure. AB - To determine whether the human estrogen receptor requires ligand to bind to its cognate estrogen receptor element (ERE) in vivo, we have examined the structure of chromatin at a chromosomally integrated ERE-URA3 reporter gene in yeast, and the influence of ligand bound and ligand free estrogen receptors on that structure. Using indirect end-labelling to map DNaseI and micrococcal nuclease sensitive sites, we found that receptor induced alterations in chromatin structure were completely dependent upon the presence of estradiol. These same alterations in chromatin structure were induced by a truncated estrogen receptor with both TAF-1 and TAF-2 transactivation functions deleted, suggesting that DNA binding per se disrupts chromatin structure. These results support models in which the estrogen receptor requires ligand to bind to the ERE in vivo. PMID- 1408753 TI - Cleavage of synthetic substrates containing non-nucleotide inserts by restriction endonucleases. Change in the cleavage specificity of endonuclease SsoII. AB - A study was made of the interaction between restriction endonucleases recognizing CCNGG (SsoII and ScrFI) or CCA/TGG (MvaI and EcoRII) DNA sequences and a set of synthetic substrates containing 1,3-propanediol, 1,2-dideoxy-D-ribofuranose or 9 [1'-hydroxy-2'-(hydroxymethyl)ethoxy] methylguanine (gIG) residues replacing either one of the central nucleosides or dG residues in the recognition site. The non-nucleotide inserts (except for gIG) introduced into the recognition site both increase the efficiency of SsoII and change its specificity. A cleavage at the noncanonical position takes place, in some cases in addition to the correct ones. Noncanonical hydrolysis by SsoII occurs at the phosphodiester bond adjacent to the point of modification towards the 5'-end. With the guanine base returned (the substrate with gIG), the correct cleavage position is restored. ScrFI specifically cleaves all the modified substrates. DNA duplexes with non nucleotide inserts (except for the gIG-containing duplex) are resistant to hydrolysis by MvaI and EcoRII. Prompted by the data obtained we discuss the peculiarities of recognition by restriction endonucleases of 5-membered DNA sequences which have completely or partially degenerated central base pairs. It is suggested that SsoII forms a complex with DNA in an 'open' form. PMID- 1408754 TI - Spontaneous chromosome rearrangements in the protozoan Giardia lamblia: estimation of mutation rates. AB - Subcloned lines of the WB strain of Giardia lamblia contain polymorphic ribosomal RNA (rRNA) encoding chromosomes (Le Blancq et al., Nucl. Acids Res. 1991, 19, 4405-4412). We show that in a continuously propagated culture of G.lamblia trophozoites the proportion of trophozoites with rearranged rRNA encoding chromosomes gradually increases, consistent with the high mutation rate of about 1% per cell per division cycle. This conclusion is based on the finding in one experiment that after about 8 division cycles 20% of the population consisted of independent mutants, while after approximately 100 division cycles 87.5% of the population were independent mutants. In a second experiment, approximately 38% and 71.5% of the trophozoites were independent mutants after approximately 9 and approximately 100 division cycles, respectively. The data show that the genome of the WB strain of G.lamblia has a highly recombinogenic phenotype. Extensive karyotype heterogeneity has also been observed among recently isolated G.lamblia strains obtained from a defined geographic area (Korman et al., J. Clin. Invest. 1992, 89, 1725-1733) suggesting that a high mutation rate might also occur in vivo. PMID- 1408755 TI - Chemical and enzymatic incorporation of N2-(p-n-butylphenyl)-2'-deoxyguanosine into an oligodeoxyribonucleotide. AB - An 18mer oligodeoxyribonucleotide containing a N2-(p-n-butylphenyl)-2' deoxyguanosine (BuPdG) residue at the 3' end has been synthesized by both chemical and enzymatic methods. Chemical synthesis involved attachment of 5'-DMT BuPdG as the 3'-H-phosphonate to uridine-controlled pore glass (CPG), followed by extension via H-phosphonate chemistry. After oxidation of the backbone, deprotection of bases, and removal from CPG, the uridine residue was removed by periodate cleavage and beta-elimination. The resulting oligomer 3'-phosphate was digested with alkaline phosphatase to give the free BuPdG-18mer. E.coli DNA polymerase I (Klenow) incorporated BuPdGTP at the 3' end of the corresponding 17mer primer annealed to a complementary 29mer template, and the properties of this product were identical to those of chemically synthesized BuPdG-18mer. E.coli DNA polymerase I (Klenow) was unable to extend the BuPdG-18mer, and the 3' to 5' exonuclease activity of the enzyme was unable to remove the modified nucleotide. PMID- 1408756 TI - Gilvocarcin V exhibits both equilibrium DNA binding and UV light induced DNA adduct formation which is sequence context dependent. AB - The relative degree of both equilibrium binding and of ultraviolet light induced adduct formation for the antitumor antibiotic gilvocarin V with two hexaecamer DNA sequence isomers, d[ATATATAGCTATATAT]2 and d[AAAAAAAGCTTTTTTT]2, was assessed. The experiments reveal that gilvocarin V binds, under equilibrium conditions, and reacts, in the presence of exogenously applied UV light, more efficiently with the alternating purine:pyrimidine sequence hexadecamer than the homopurine:homopyrimidine duplex at identical gilvocarcin V to DNA duplex ratios. DNAse I digests of adduct containing duplexes derived from the d[AAAAAAAGCTTTTTTT]2 duplex, identified and isolated using gel shift assays employing denaturing polyacrylamide gels, confirm that gilvocarcin V adducts can be formed with thymine residues but suggest that adduct formation with either adenine or guanine residues is also possible. PMID- 1408757 TI - Chimeric DNA-RNA hammerhead ribozymes have enhanced in vitro catalytic efficiency and increased stability in vivo. AB - Subsequent to the discovery that RNA can have site specific cleavage activity, there has been a great deal of interest in the design and testing of trans-acting catalytic RNAs as both surrogate genetic tools and as therapeutic agents. We have been developing catalytic RNAs or ribozymes with target specificity for HIV-1 RNA and have been exploring chemical synthesis as one method for their production. To this end, we have chemically synthesized and experimentally analyzed chimeric catalysts consisting of DNA in the non-enzymatic portions, and RNA in the enzymatic core of hammerhead type ribozymes. Substitutions of DNA for RNA in the various stems of a hammerhead ribozyme have been analyzed in vitro for kinetic efficiency. One of the chimeric ribozymes used in this study, which harbors 24 bases of DNA capable of base-pairing interactions with an HIV-1 gag target, but maintains RNA in the catalytic center and in stem-loop II, has a sixfold greater kcat value than the all RNA counterpart. This increased activity appears to be the direct result of enhanced product dissociation. Interestingly, a chimeric ribozyme in which stem-loop II (which divides the catalytic core) is comprised of DNA, exhibited a marked reduction in cleavage activity, suggesting that DNA in this region of the ribozyme can impart a negative effect on the catalytic function of the ribozyme. DNA-RNA chimeric ribozymes transfected by cationic liposomes into human T-lymphocytes are more stable than their all-RNA counterparts. Enhanced catalytic turnover and stability in the absence of a significant effect on Km make chimeric ribozymes favorable candidates for therapeutic agents. PMID- 1408758 TI - Extension of base mispairs by Taq DNA polymerase: implications for single nucleotide discrimination in PCR. AB - Thermus aquaticus (Taq) DNA polymerase was used to measure the extension efficiency for all configurations of matched and mismatched base pairs at template-primer 3'-termini. The transition mispairs, A(primer).C, C.A, G.T, and T.G were extended 10(-3) to 10(-4)-fold less efficiently than their correctly paired counterparts. Relative efficiencies for extending transversion mispairs were 10(-4) to 10(-5) for T.C and T.T, about 10(-6) for A.A, and less than 10(-6) for G.A, A.G, G.G and C.C. The transversion mispair C(primer).T was extended with high efficiency, about 10(-2) compared to a correct A.T basepair. The unexpected ease of extending the C.T mismatch was not likely to have been caused by primer template misalignment. Taq polymerase was observed to bind with similar affinities to each of the correctly paired and mispaired primer-template 3'-ends. Thus, the failure of Taq polymerase to extend mismatches efficiently appears to be an intrinsic property of the enzyme and not due to an inability to bind to 3' terminal mispairs. For almost all of the mispairs, C.T being the exception, Taq polymerase exhibits about 100 to 1000-fold greater discrimination against mismatch extension compared to avian myeloblastosis reverse transcriptase and HIV 1 reverse transcriptase which extend most mismatched basepairs permissively. Relative mismatch extension efficiencies for Taq polymerase were measured at 45 degrees C, 55 degrees C and 70 degrees C and found to be independent of temperature. The mispair extension data should be important in designing experiments using PCR to distinguish between sequences that vary by a single nucleotide. PMID- 1408759 TI - Construction of human XRCC1 minigenes that fully correct the CHO DNA repair mutant EM9. AB - The human gene that corrects the DNA repair defect of the CHO cell mutant EM9 is designated XRCC1 and is the first human gene to be cloned that has an established role in DNA strand-break repair. In this study, either an XRCC1 cosmid genomic fragment or synthetic oligonucleotides were ligated to an incomplete XRCC1 cDNA to generate two full-length XRCC1 cDNA constructs. The ability of these minigene constructs to restore normal levels of sister chromatid exchange (SCE) to EM9 upon transfection was demonstrated, and the transfectants grew at normal rates in selective medium that is fully toxic to EM9 cells. Constructs in which the XRCC1 open reading frame (ORF) was transcribed from the SV40 early promoter or the genomic XRCC1 native promoter were compared in their efficiency of correction. EM9 transfectants derived from the SV40 promoter displayed fewer SCEs and lower sensitivity to CldUrd than either AA8 wild-type cells or transfectants containing the ORF transcribed from the native promoter. PMID- 1408760 TI - Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication--potential effectiveness against most presently sequenced HIV-1 isolates. AB - Several mono-, di-, tetra-, penta- and nonaribozymes were developed. These multitarget-ribozymes were targeted to cleave HIV-1 env RNA at up to nine different conserved sites. Each multitarget-ribozyme consisted of a chain of up to nine hammerhead motifs, each flanked by a different targeting sequence. The multitarget-ribozymes were functional in vitro and gave rise to multiple, specific partial and/or complete RNA digestion products. Per RNA copy, multitarget-ribozymes were more efficient than monoribozymes or ribozymes targeting a subset of the same sites. In contrast to monoribozymes, a 400nt nonaribozyme, targeted to cleave at nine different sites within a 1.3kb HIV-1 env RNA substrate, was active and showed the same specificity of cleavage when it was part of a large 3.3kb transcript. We conclude that multitarget-ribozymes retain the specificity of monoribozymes, but they are more efficient per ribozyme RNA copy and they remain active when they are part of a large transcript. A tetra-, penta- or nonaribozyme under control of the SV40 late promoter, the beta-actin gene promoter or the HIV-1 LTR, respectively, were cotransfected with the infectious HIV-1 DNA clone pNL4-3 into permissive HeLa T4 cells. Each cotransfection resulted in a specific inhibition of HIV-1 replication as determined by syncytia formation and p24 antigen release. In addition, coexpression of the nonaribozyme with an HIV-1 env RNA transcript resulted in the specific dramatic reduction of the env transcript. We conclude that the multitarget-ribozymes are also functional intracellularly. A nucleotide sequence comparison of the target sites indicates that the multitarget-ribozymes could potentially be effective against all thirty HIV-1 isolates presently sequenced. Their use may help to slow the selection of viral escape mutants and thereby prolong their effectiveness. We anticipate that multitarget-ribozymes will also be more effective in the successful targeting of less variable cellular RNAs. PMID- 1408762 TI - Integration of image analysis and robotics into a fully automated colony picking and plate handling system. AB - We describe here the integration of image analysis and robotics to produce a fully automated colony picking/plate handling system. Biological tests were performed to verify its performance in terms of sterilisation and accuracy of picking. The machine was then used by a single operative to pick a 36,000 clone cDNA library in approximately 42 hrs over 5 days. PMID- 1408761 TI - Construction and use of lambda PL promoter vectors for direct cloning and high level expression of PCR amplified DNA coding sequences. AB - A set of plasmid vectors which allow single-step cloning and expression of PCR amplified DNA coding sequences has been constructed. The vectors contain the phage lambda PL promoter, a synthetic translation initiation region (TIR), and convenient cloning sites. The cloning sites provide all or part of an AUG translation initiation codon and facilitate the precise fusion of target DNA sequences to vector transcriptional and translational signals. The vectors were constructed with synthetic TIRs because there is evidence which suggests that the efficiency of the phage lambda cII gene TIR present in the parental vector depends strongly on information contained within the cII N-terminal coding sequence. Bovine brain 14-3-3 eta chain cDNA was PCR-amplified and used to demonstrate the expression capacity of the newly constructed vectors. A significant increase in expression of 14-3-3 protein was observed when synthetic TIRs were used in the place of the cII TIR. Expression levels vary from 15% to 48% of total cell protein. The effects of a reported translational enhancer from phage T7 on expression of the 14-3-3 protein are also discussed. The vectors should be generally useful for high level heterologous protein expression in Escherichia coli. PMID- 1408763 TI - Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. AB - Transcription factors containing the POU-domain have been shown to be important regulators of tissue-specific gene expression in the pituitary and lymphoid cells. Using a polymerase chain reaction (PCR)-based strategy, we have searched for similar factors that may be expressed in adult human pancreatic islets. This approach resulted in the amplification of sequences encoding the octamer binding proteins Oct1 and Oct3 (also called Oct4). The isolation of cDNAs encoding Oct3 revealed the expression of two isoforms of this transcription factor termed Oct3A and Oct3B that are generated by alternative splicing. Human Oct3A and Oct3B are composed of 360 and 265 amino acids, respectively, of which the 225 amino acids at the COOH-termini are identical. The sequence of human Oct3A shows 87% amino acid identity with mouse Oct3. Reverse-transcriptase PCR showed low levels of expression of both Oct3A and Oct3B mRNA in all adult human tissues examined. We also isolated and characterized the human Oct3 gene (OTF3) and a related gene, OTF3C. The human Oct3 gene, localized to human chromosome 6 in the region of the MHC complex, spans about 7 kb and consists of five exons. The Oct3-related gene, OTF3C, is a retroposon and has been localized to human chromosome 8. Southern blotting and PCR amplification of human DNA indicated the presence of other OTF3 related genes as has been previously noted in the mouse. Two polymorphisms which can be typed using PCR were identified in OTF3 which will facilitate genetic studies of this gene. PMID- 1408764 TI - Drug targeting: synthesis and endocytosis of oligonucleotide-neoglycoprotein conjugates. AB - Inhibition of gene expression by antisense oligonucleotides is limited by their low ability to enter cells. Knowing that sugar binding receptors, also called membrane lectins, efficiently internalize neoglycoproteins bearing the relevant sugar, 6-phosphomannose, for instance, oligonucleotides--substituted on their 5' end with either a fluorescent probe or a radioactive label on the one hand, and bearing a thiol function on their 3'-end, on the other hand,--were coupled onto 6 phosphomannosylated proteins via a disulfide bridge. The oligonucleotide bound to 6-phosphomannosylated serum albumin is much more efficiently internalized roughly 20 times than the free oligonucleotide. Although most of the oligonucleotides are associated with vesicular compartments, oligonucleotides after releasing from the carrier by reduction of the disulfide bridge may find their way to reach the cytosol and then lead to an increase in the efficiency of the oligonucleotides. PMID- 1408765 TI - Identification of the motifs within the tobacco mosaic virus 5'-leader responsible for enhancing translation. AB - The leader (called omega) of tobacco mosaic virus RNA enhances translation in both eukaryotes and prokaryotes. Although little secondary structure is predicted to exist within omega, the primary sequence of the 68 base leader is highly organized. Three copies of an eight base direct repeat and a (CAA)n region represent the two motifs found in the leaders of many TMV strains, and together these comprise 72% of omega. In previous deletion studies, no mutants exhibited loss-of-function, suggesting that functional redundancy exists within omega. We report here that a more comprehensive deletion analysis identified the motifs involved in translational enhancement. In a separate approach, oligonucleotides containing the sequence of each motif were used to construct leaders that varied in the number and configuration of the motifs. beta-Glucuronidase mRNA constructs containing these mutant leaders were synthesized in vitro and their translational efficiency measured in vivo following mRNA delivery to carrot protoplasts via electroporation. A combination of one copy of the 8 base direct repeat and a 25 base (CAA)n region was identified as the core regulatory element, although the (CAA)n motif is more critical. Two copies of the (CAA)n region are sufficient to confer a high level of enhancement and a leader composed of multiple copies of the direct repeat is moderately enhancing. Thus, these two motifs are functionally redundant. PMID- 1408767 TI - The 18S ribosomal RNA gene of a crustacean decapod Oedignathus inermis: a comparison with Artemia salina gene. PMID- 1408766 TI - Cloning of human and bovine homologs of SNF2/SWI2: a global activator of transcription in yeast S. cerevisiae. AB - We performed positional cloning of genes carried on yeast artificial chromosomes that span a human translocation breakpoint associated with a human disease and isolated by chance human and bovine genes with strong homology to the S. cerevisiae genes, SNF2/SWI2 and STH1, and the D. melanogaster gene brahma. We report here sequence analysis, expression data, and functional studies for this human SNF2-like gene (hSNF2L) and its bovine homolog (bovSNF2L). Despite strong homology at the amino acid level, hSNF2L is not capable of complementing the yeast mutations snf2 or sth1 in S. cerevisiae. Furthermore, in contrast to SNF2 itself, a fusion protein consisting of the DNA binding domain of LexA and hSNF2L did not transactivate a reporter gene downstream of LexA binding sites in a yeast expression system. The strong similarity between hSNF2L and these yeast and drosophila genes suggest that the mammalian genes are part of an evolutionarily conserved family that has been implicated as global activators of transcription in yeast and fruitflies but whose function in mammals remains unknown. PMID- 1408768 TI - Nucleotide sequence of the genes encoding the three largest subunits of the DNA dependent RNA polymerase from the archaeum Thermococcus celer. PMID- 1408769 TI - Nucleotide sequence of the replication region of the Nostoc PCC 7524 plasmid pDU1. PMID- 1408770 TI - Identification of a tRNA(Gln) ochre suppressor in Saccharomyces cerevisiae. PMID- 1408771 TI - Momordin II, a ribosome inactivating protein from Momordica balsamina, is homologous to other plant proteins. PMID- 1408773 TI - BpuAI, a novel BbsI and BbvII isoschizomer from Bacillus pumilus recognizing 5' GAAGAC-3'. PMID- 1408772 TI - A putative homolog of U2AF65 in S. cerevisiae. PMID- 1408774 TI - A novel method for rapid genomic walking using lambda vectors. PMID- 1408775 TI - A novel method for isolation of large insert DNA from recombinant lambda DNA. PMID- 1408776 TI - cDNA cloning of 5' terminal regions. PMID- 1408777 TI - A hit-and-run system for targeted genetic manipulations in yeast. PMID- 1408778 TI - Electroporation of viral transactivator proteins into lymphocyte suspension cells. PMID- 1408779 TI - Band-stab PCR: a simple technique for the purification of individual PCR products. PMID- 1408780 TI - An alternative, rapid method of plant DNA extraction for PCR analyses. PMID- 1408782 TI - A novel strategy for site-directed chemical reactions in single stranded DNA- absorption and NMR spectroscopic studies of model compounds. AB - A new and simple model enabling a chemical species to be brought to a preselected site in single strand DNA is reported. Two oligonucleotides containing a propanediol linkage were hybridized to their complementary sequences with an extra-base opposite the propanediol derivative. Absorption studies results shown that the addition of a bisacridine derivative strongly increased the stabilities of both duplexes when added in a 1:1 ratio. NMR studies on one of these duplexes brought evidence of the intercalation of the bisacridine at the position involving the propanediol linkage. These results suggest that this system could be used to target a specific reaction at a preselected position using the bisacridine derivative as carrier for the reactive species. PMID- 1408783 TI - Determination of lysine residues affinity labeled in the active site of yeast RNA polymerase II(B) by mutagenesis. AB - In a previous study, yeast RNA polymerase II(B) was affinity labeled with two nucleotide derivatives (III and VIII) (1). In both cases, the labeled site was localized to the C-terminal part of the B150 subunit. The potential target lysyl residues of derivative III were mapped to the conserved domain H, between Asn946 and Met999. In the present work, we have mutagenized to arginine the five lysines present in domain H. Three lysines can be replaced, individually or simultaneously, without affecting cell growth, and each mutated enzyme can still be affinity labeled. Hence one or both of the other two lysyl residues, Lys979 and Lys987, is the target of the affinity reagent. These two lysines were each found to be essential for cell viability. Derivative VIII labeled another domain in addition to domain H. Supported by analogous results obtained for E. coli RNA polymerase using derivative VIII (2), we hypothesized that the second domain labeled by this derivative in the B150 subunit was domain I. Mutagenesis of the unique lysine present in domain I demonstrated that Lys 1102 was the target of derivative VIII. These results indicate that in both prokaryotic and eukaryotic RNA polymerases, domains H and I are in close proximity and participate to the active site. PMID- 1408781 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1408784 TI - A new approach to the analysis of DNase I footprinting data and its application to the TFIIIA/5S DNA complex. AB - We have re-examined DNase I footprinting data for the binding of transcription factor IIIA (TFIIIA) to the 5S RNA gene, taking into account the protein-DNA contacts observed in the crystal structure of the DNase I/DNA complex (1, 2). This structure was not available when many of the original footprinting experiments on the TFIIIA/DNA complex were performed. In this way the pattern of DNase I cleavage can be interpreted to map out with greater precision the regions on the 5S DNA occupied by TFIIIA. Then, assuming the binding site for a zinc finger may be the same as that found in the structure of the zinc-finger protein Zif268/DNA complex (3), and taking into account footprinting data for truncated forms of TFIIIA, the TFIIIA zinc-fingers were fitted within the permitted regions. On the basis of this, an alignment of the zinc-fingers of TFIIIA with its DNA binding site is proposed, which combines features of earlier models (4). PMID- 1408785 TI - The yeast actin intron contains a cryptic promoter that can be switched on by preventing transcriptional interference. AB - We show that the single intron of the actin gene of the yeast Saccharomyces cerevisiae contains a cryptic promoter for transcription of the second exon. This promoter is inactive in the normal actin gene, but can be activated when the actin gene promoter is deleted. An identical activation was induced by placing efficient transcriptional terminators at position 61 of the 309 bp intron. In all cases transcripts with identical 5' ends close to the boundary of the intron and the second exon were produced. These results indicate that the cryptic promoter in the actin intron is occluded in the normal actin gene by transcriptional interference with the actin gene promoter. Transcription initiation near the intron/exon 2 boundary is enabled by protection from traversing polymerases, that initiated transcription at the upstream located actin gene promoter. A partial promoter protection using leaky terminators resulted in small amounts of transcripts initiated from the cryptic promoter. Although we do not know any function of the cryptic promoter in actin gene expression, it is tentative to speculate that the cryptic intron promoter might be a relict of a promoter that was functional earlier in evolution. PMID- 1408787 TI - Heteronuclear NMR of DNA with the heteronucleus in natural abundance: facilitated assignment and extraction of coupling constants. AB - Two heteronuclear proton-carbon NMR experiments are applied to the DNA-octamer d(TTGGCCAA)2 with carbon in natural abundance. They lead to a complete assignment of the carbon resonances of the sugars and bases. In addition, several heteronuclear coupling constants, proton-carbon as well as proton-phosphorous and phosphorous-carbon, were determined. The information can be obtained in a reasonable measuring time and offers valuable information for a detailed picture of DNA structure. PMID- 1408786 TI - Involvement of the size and sequence of the anticodon loop in tRNA recognition by mammalian and E. coli methionyl-tRNA synthetases. AB - The rates of the cross-aminoacylation reactions of tRNAs(Met) catalyzed by methionyl-tRNA synthetases from various organisms suggest the occurrence of two types of tRNA(Met)/methionyl-tRNA synthetase systems. In this study, the tRNA determinants recognized by mammalian or E. coli methionyl-tRNA synthetases, which are representative members of the two types, have been examined. Like its prokaryotic counterpart, the mammalian enzyme utilizes the anticodon of tRNA as main recognition element. However, the mammalian cytoplasmic elongator tRNA(Met) species is not recognized by the bacterial synthetase, and both the initiator and elongator E. coli tRNA(Met) behave as poor substrates of the mammalian cytoplasmic synthetase. Synthetic genes encoding variants of tRNAs(Met), including the elongator one from mammals, were expressed in E. coli. tRNAs(Met) recognized by a synthetase of a given type can be converted into a substrate of an enzyme of the other type by introducing one-base substitutions in the anticodon loop or stem. In particular, a reduction of the size of the anticodon loop of cytoplasmic mammalian elongator tRNA(Met) from 9 to 7 bases, through the creation of an additional Watson-Crick pair at the bottom of the anticodon stem, makes it a substrate of the prokaryotic enzyme and decreases its ability to be methionylated by the mammalian enzyme. Moreover, enlarging the size of the anticodon loop of E. coli tRNA(Metm) from 7 to 9 bases, by disrupting the base pair at the bottom of the anticodon stem, renders the resulting tRNA a good substrate of the mammalian enzyme, while strongly altering its reaction with the prokaryotic synthetase. Finally, E. coli tRNA(Metf) can be rendered a better substrate of the mammalian enzyme by changing its U33 into a C. This modification makes the sequence of the anticodon loop of tRNA(Metf) identical to that of cytoplasmic initiator tRNA(Met). PMID- 1408788 TI - The conformational variability of an adenosine.inosine base-pair in a synthetic DNA dodecamer. AB - A crystal structure analysis of the synthetic deoxydodecamer d(CGCAAATTIGCG) which contains two adenosine.inosine (A.I) mispairs has revealed that, in this sequence, the A.I base-pairs adopt a A(anti).I(syn) configuration. The refinement converged at R = 0.158 for 2004 reflections with F greater than or equal to 2 sigma(F) in the range 7.0-2.5A for a model consisting of the DNA duplex and 71 water molecules. A notable feature of the structure is the presence of an almost complete spine of hydration spanning the minor groove of the whole of the (AAATTI)2 core region of the duplex. pH-dependent ultraviolet melting studies have suggested that the base-pair observed in the crystal structure is, in fact, a protonated AH+ (anti).I(syn) species and that the A.I base-pairs in the sequence studied display the same conformational variability as A.G mispairs in the sequence d(CGCAAATTGGCG). The AH+(anti).I(syn) base-pair predominates below pH 6.5 and an A(anti).I(anti) mispair is the major species present between pH 6.5 and 8.0. The protonated base-pairs are held together by two hydrogen bonds one between N6(A) and O6(I) and the other between N1(A) and N7(I). This second hydrogen bond is a direct result of the protonation of the N1 of adenosine. The ultraviolet melting studies indicate that the A(anti).I(anti) base-pair is more stable than the A(anti).G(anti) base-pair but that the AH+(anti).I(syn) base pair is less stable than its AH+(anti).G(syn) analogue. Possible reasons for this observation are discussed. PMID- 1408789 TI - Cooperative effects of C/EBP-like and NF kappa B-like binding sites on rat serum amyloid A1 gene expression in liver cells. AB - Serum amyloid A (SAA) is a major acute-phase protein synthesized and secreted mainly by the liver. In response to inflammation, its expression is increased by 1000-fold, primarily because of a 200-fold increase in the rates of SAA gene transcription. We have shown that when 304 bp of 5' flanking region of the rat SAA1 gene is fused to a reporter gene, the chloramphenicol acetyltransferase (CAT) gene, CAT activity is induced in a cell-specific manner in response to conditioned media prepared from activated mixed lymphocyte cultures and recombinant interleukin-1. In this study, deletion of the SAA1 promoter to -120 bp with respect to the transcriptional start site did not diminish promoter activity; however, deletion to -94 bp renders the promoter completely inactive. Functional analysis have demonstrated that a 66-bp DNA fragment spanning -138 bp to -73 bp could confer cytokine responsiveness to a heterologous thymidine kinase promoter. Within this 66-bp responsive element resided an NF kappa B-like-binding site and a C/EBP-like-binding site. Although each binding site alone could confer responsiveness when stimulated with conditioned media and TPA, the response was much weaker than that observed when both sites were present. Moreover, site specific mutations of either binding site completely abolished SAA1 promoter activity. Taken together, these results suggest a functional importance for and cooperative interaction of these two nuclear-factor binding sites in the cytokine induced expression of the rat SAA1 gene. PMID- 1408790 TI - Transcription frequency modulates the efficiency of an attenuator preceding the rpoBC RNA polymerase genes of Escherichia coli: possible autogenous control. AB - Expression of the rpoBC genes encoding the beta and beta' RNA polymerase subunits of Escherichia coli is autogenously regulated. Although previous studies have demonstrated a post-transcriptional feedback mechanism, complex transcriptional controls of rpoBC expression may also contribute. We show that an attenuator (rpoBa) separating the ribosomal protein (rpl) genes from the rpoBC genes in the rplKAJLrpoBC gene cluster is modulated in its efficiency in response to changes in the frequency of transcription initiated by promoters located upstream. A series of rplJLrpoBalacZ transcriptional fusions was constructed on lambda vectors in which transcription into the rpoBa attenuator was varied by using a variety of promoters with different strengths. beta-galactosidase assays performed on monolysogens of the recombinant phage show that with transcription increasing over a 40-fold range, readthrough of rpoBa decreases from 61% to 19%. In contrast, two other well-characterized terminators show nearly constant efficiencies over a similar range of transcription frequencies. Using a set of phage P22 ant promoter variants with single-nucleotide changes in the promoter consensus sequences also demonstrates that the modulation of rpoBa function appears to be unrelated to the phenomenon of 'factor-independent antitermination' reported by others. The implications for autogenous control of RNA polymerase synthesis are discussed. PMID- 1408791 TI - Characterisation of a boundary between satellite III and alphoid sequences on human chromosome 10. AB - Alphoid and satellite III sequences are arranged as large tandem arrays in the centromeric regions of human chromosomes. Several recent studies using in situ hybridisation to investigate the relative positions of these sequences have shown that they occupy adjacent but non-overlapping domains in metaphase chromosomes. We have analysed the DNA sequence at the junction between alphoid and satellite III sequences in a cosmid previously mapped to chromosome 10. The alphoid sequence consists of tandemly arranged dimers which are distinct from the known chromosome 10-specific alphoid family. Polymerase chain reaction experiments confirm the integrity of the sequence data. These results, together with pulsed field gel electrophoresis data place the boundary between alphoid and satellite III sequences in the mapping interval 10 centromere-10q11.2. The sequence data shows that these repetitive sequences are separated by a partial L1 interspersed repeat sequence less than 500bp in length. The arrangement of the junction suggests that a recombination event has brought these sequences into close proximity. PMID- 1408792 TI - Repair of UV-induced (6-4)photoproducts measured in individual genes in the Drosophila embryonic Kc cell line. AB - The nucleotide excision repair (NER; dark-repair) of (6-4)photoproducts ((6 4)PPs) was assayed in cells from a permanent Drosophila melanogaster embryonic cell line, Kc, after exposure to 20 or 40 J/m2 ultraviolet (UV) light. Induction rates in the transcriptionally active genes Gart and Notch as well as in the inactive white locus is similar. They are formed with a frequency of about one third of that of cyclobutane pyrimidine dimers (CPDs). In all three genes, (6 4)PPs are repaired with the same rate and to the same extent: 31% of the (6-4)PPs are removed in 4 hours post-irradiation and after 16 hours repair is nearly complete. In none of the three genes strand-specific repair was found. Exposure of cells that were irradiated with 40 J/m2 UV to photoreactivating light for 1 hour prior to dark-repair incubation, resulted in enhanced repair of (6-4)PPs. PMID- 1408793 TI - End extension repair of introduced targeting vectors mediated by homologous recombination in mammalian cells. AB - We have studied the mechanism of targeted recombination in mammalian cells using a hemizygous adenine phosphoribosyltransferase-deficient (APRT-) Chinese hamster ovary (CHO) cell mutant as a recipient. Three structurally different targeting vectors with a 5' or a 3', or both, end-deleted aprt sequence, in either a closed circular or linear form, were transfected to the cells with a mutated aprt gene by electroporation. APRT-positive (APRT+) recombinant clones were selected and analyzed to study the gene correction events of the deletion mutation. Some half of 58 recombinant clones obtained resulted from corrections of the deleted chromosomal aprt gene by either gene replacement or gene insertion, a mechanism which is currently accepted for homologous recombination in mammalian cells. However, the chromosomal sequence in the remaining half of the recombinants remained uncorrected but their truncated end of the aprt gene in the incoming vectors was corrected by extending the end beyond the region of homology to the target locus; the corrected vector was then randomly integrated into the genome. This extension, termed end extension repair, was observed with all three vectors used and was as far as 4.6-kilobase (kb) or more long. It is evident that the novel repair reaction mediated by homologous recombination, in addition to gene replacement and gene insertion, is also involved in gene correction events in mammalian cells. We discuss the model which may account for this phenomenon. PMID- 1408794 TI - Thyroid hormone alters the DNA binding properties of chicken thyroid hormone receptors alpha and beta. AB - The effects of thyroid hormone agonists on thyroid hormone receptor (TR)/DNA complex formation was investigated to elucidate the mechanism by which TRs transactivate genes in response to ligand. The data, obtained from gel shift experiments, indicate that thyroid hormones alter the conformation of TRs bound to DNA, irrespective of if the element is occupied by monomeric TR, homodimeric TR/TR, or heterodimeric complexes with the retinoid receptors RAR or RXR. Furthermore, triiodo-thyronine (T3) prevents 2 TR molecules from binding to oligonucleotides containing direct repeats or inverted palindromes of the consensus AGGTCA motif, an effect that was not detected with palindromic elements. Heterodimers bound to direct repeats were less affected: RXR/TR were fully and RAR/TR complexes partially resistant to thyroid hormone. The data suggest that a ligand-induced conformational change in TR prevents double TR occupancy of a response element containing 2 direct repeats of the consensus binding motif, possibly by steric hindrance, whereas such an event does not prevent TR/RXR heterodimers from binding to DNA. Finally, our data show that a monomeric, liganded TR bound preferentially to the second half site in a AGGTCActcaAGGTCA element, and therefore indicate that nucleotides adjacent to the consensus half site contribute to binding specificity. PMID- 1408795 TI - How M.MspI and M.HpaII decide which base to methylate. AB - The HpaII methylase (M.HpaII) recognizes the sequence CCGG and methylates the inner cytosine residue. The MspI methylase (MspI) recognizes the same sequence but methylates the outer cytosine residue. Both methylases have the usual architecture of 10 well-conserved motifs surrounding a variable region, responsible for sequence specific recognition, that is quite different in the two methylases. We have constructed hybrids between these two methylases and studied their methylation properties. A hybrid containing the variable region and C terminal sequences from M.MspI methylates the outer cytosine residue. A second hybrid identical to the first except that the variable region derives from the M.HpaII methylates the inner cytosine residue. Thus the choice of base to be methylated within the recognition sequence is determined by the variable region. PMID- 1408797 TI - Lability of monofunctional cis-platinum adducts: role of DNA double helix. AB - Recently, we have shown that the adduct formed in the reaction between the platinum-triamine complex cis-[Pt(NH3)2(N7-N-methyl-2-diazapyrenium)Cl]2+ and one single-stranded oligonucleotide was stable but became labile as soon as the platinated oligonucleotide was paired with its complementary strand (Gaucheron et al. Proc. Natl. Acad. Sci. USA 88, 3516-3519 (1991)). To generalize this finding we have now studied large DNA fragments containing several adducts. The stability of the adducts within single-stranded DNA is demonstrated by absorption spectrophotometry and by replication mapping experiments. Several approaches are used to prove the lability of the adducts within double-stranded DNA. Replication mapping experiments reveal that an unmodified single-stranded DNA when mixed with double-stranded DNA modified by the platinum-triamine complex behaves as a single stranded DNA modified by the triamine complex. After double-stranded DNA is modified by the platinum-triamine complex, intrastrand and interstrand cross links are progressively formed during subsequent incubation as revealed by transcription mapping experiments and gel electrophoresis under denaturing conditions. Finally, replication mapping experiments show that the lability of the adducts within a double-stranded DNA depends upon the nature of the flanking nucleotide residues. All these results support the proposal that the DNA double helix acts as a catalyst in the reaction between DNA, cis diamminedichloroplatinum(II) and N-methyl-2,7-diazapyrenium. PMID- 1408796 TI - Isolation of genomic DNA encoding transcription factor TFIID from Acanthamoeba castellanii: characterization of the promoter. AB - We have isolated a genomic clone encoding Acanthamoeba castellanii TFIID. The clone contains the entire TFIID gene, 300 bp of 5' promoter sequences and several hundred base pairs of 3' non-coding sequence. The coding region is interrupted by two short introns, but is otherwise identical to Acanthamoeba TFIID cDNA. Comparisons between forty four Acanthamoeba intron 5' and 3' boundaries suggest a 5' splice site consensus of GTACG(T/C) and a 3' consensus of CAG. We determined the position of the transcription initiation site used in vivo, and show that the same site is used in vitro by homologous nuclear extracts. Deletion analysis of the promoter region shows that the minimal promoter required for efficient expression in vitro is located between -97 and +4 relative to the transcription start site. Three regions within the promoter are important for transcription in vitro; sequences between -97 and -35, the TATAAA box and the initiation region. The initiation region is dispensable but appears to position the transcription start site relative to the TATAAA box. The TATAAA box is absolutely required for transcription initiation whereas the upstream region stimulates transcription approximately five-fold. PMID- 1408798 TI - Detection of single base differences using biotinylated nucleotides with very long linker arms. AB - A simple primer extension method for detecting nucleotide differences is based on the substitution of mobility-shifting analogs for natural nucleotides (1). This technique can detect any single-base difference that might occur including previously unknown mutations or polymorphisms. Two technical limitations of the original procedure have now been addressed. First, switching to Thermococcus litoralis DNA polymerase has eliminated variability believed to be due to the addition of an extra, non-templated base to the 3' end of DNA by Taq DNA polymerase. Second, with the analogs used in the original study, the mobility shift induced by a single base change can usually be resolved only in DNA segments 200 nt or smaller. This size limitation has been overcome by synthesizing biotinylated nucleotides with extraordinarily long linker arms (36 atom backbone). Using these new analogs and conventional sequencing gels (0.4 mm thick), mutations in the human beta-hexosaminidase alpha and CYP2D6 genes have been detected in DNA segments up to 300 nt in length. By using very thin (0.15 mm) gels, single-base polymorphisms in the human APOE gene have been detected in 500-nt segments. PMID- 1408799 TI - Synthesis of the diastereomers of thymidine glycol, determination of concentrations and rates of interconversion of their cis-trans epimers at equilibrium and demonstration of differential alkali lability within DNA. AB - 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol) is a major product of the reaction of thymidine with reactive oxygen species, including those generated by ionizing radiation. Thymidine glycol exists as 2 diastereomeric pairs by virtue of the chirality of the C(5) and C(6) atoms. A simple procedure is described for synthesizing and purifying each of the diastereomeric pairs separately. After brominating thymidine, the two trans 5-bromo-6-hydroxy-5,6-dihydrothymidine (thymidine bromohydrin) C(5) diastereomers were easily separated by High Performance Liquid Chromatography. Each thymidine bromohydrin was quantitatively converted to the corresponding diastereomeric thymidine glycol pair by reflux in aqueous solution. The concentrations at equilibrium of the cis (5S,6R),(5R,6S) and trans (5S,6S),(5R,6R) forms of the thymidine glycol diastereomers were determined and were 80% cis and 20% trans for the 5S pair and 87% cis and 13% trans for the 5R pair. At equilibrium, the rate of cis-trans epimerization of the two sets of diastereomers was essentially identical. The 5S diastereomeric pair was significantly more alkali labile than the 5R pair due to the higher concentration of the 5S trans epimer at equilibrium. This differential alkali lability was also manifest when the thymine glycol moiety was present in chemically oxidized poly(dA-dT).poly(dA-dT) indicating that the chemical differences between the diastereomeric pairs are preserved in DNA. These chemical differences may affect the biological properties of this important oxidative derivative of thymine in DNA. PMID- 1408800 TI - The complete nucleotide sequence of the Crossostoma lacustre mitochondrial genome: conservation and variations among vertebrates. AB - The complete mitochondrial (mt) genome of Crossostoma lacustre, a freshwater loach from mountain stream of Taiwan, has been cloned and sequenced. This fish mt genome, consisting of 16558 base-pairs, encodes genes for 13 proteins, two rRNAs, and 22 tRNAs, in addition to a regulatory sequence for replication and transcription (D-loop), is similar to those of the other vertebrates in both the order and orientation of these genes. The protein-coding and ribosomal RNA genes are highly homologous both in size and composition, to their counterparts in mammals, birds, amphibians, and invertebrates, and using essentially the same set of codons, including both the initiation and termination signals, and the tRNAs. Differences do exist, however, in the lengths and sequences of the D-loop regions, and in space between genes, which account for the variations in total lengths of the genomes. Our observations provide evidence for the first time for the conservation of genetic information in the fish mitochondrial genome, especially among the vertebrates. PMID- 1408801 TI - Two regions in human DNA polymerase beta mRNA suppress translation in Escherichia coli. AB - Although human DNA polymerase beta (DNA pol beta) shows 96% identity with rat DNA pol beta at the amino acid level, it is weakly expressed in Escherichia (E.) coli relative to the rat enzyme. The mechanism of this suppression was investigated. Pulse-chase protein labeling and steady state mRNA analysis showed that mature human DNA pol beta protein is relatively stable in E. coli and the levels of human and rat DNA pol beta mRNA were comparable indicating that the human DNA pol beta expression is suppressed at the translational level. By systematic expression analysis of a number of chimeric genes composed of human and rat cDNAs, two strong translational suppression regions were mapped in the human DNA pol beta mRNA; one was named TSR-1, corresponding to CGG encoding arginine (arg) at position 4 and the other, termed TSR-2, is located between codons 153 and 199. Since substitution of the rat Arg-4 codon with synonymous codons showed strong effects upon the expression level, we propose that the arg codon at the N terminal coding region plays a role in modulating expression. PMID- 1408802 TI - Activation and repression sequences determine the lens-specific expression of the rat gamma D-crystallin gene. AB - Rat lens nuclear extracts contain a factor that binds to position -57 to -46 of the rat gamma D-crystallin promoter region. This factor protects the sequence 5' CTGCCAACGCAG-3' in a footprint analysis. Binding to this region is crucial for maximal promoter activity in rat lens cells, but this sequence was unable to act as an enhancer when cloned in front of a heterologous promoter. A region directly upstream from this activating sequence, between position -85 to -67, acts as a strong silencer of promoter activity in non-lens cells. This silencing effect is mediated by trans-acting factor(s). Our data provide evidence for two regulatory elements in rat gamma D-crystallin gene expression, an activating sequence active in lens cells and a silencing sequence active only in non-lens cells. The factor that binds to the activating sequence could be detected only in lens cells and may be a determinant of the lens-specific expression of the gamma-crystallin genes. PMID- 1408803 TI - Two-label peak-height encoded DNA sequencing by capillary gel electrophoresis: three examples. AB - We report a modification to the peak-height encoded DNA sequencing technique of Tabor and Richardson. As in the original protocol, the sequencing reaction uses modified T7 polymerase with manganese rather than magnesium to produce very uniform incorporation of each dideoxynucleoside. To improve sequencing accuracy, two fluorescently labeled primers are employed in separate sequencing reactions. As an example, one sequencing reaction uses a FAM-labeled primer with dideoxyadenosine triphosphate and dideoxycytosine triphosphate; the concentrations of ddATP and ddCTP are adjusted to produce a 2:1 variation in the relative intensity of fragments. The second sequencing reaction uses a TAMRA labeled primer with dideoxythymidine triphosphate and dideoxyguanidine triphosphate; the concentrations of ddTTP and ddGTP are adjusted to produce a 2:1 variation in relative intensity of fragments. The pooled reaction products are separated by capillary gel electrophoresis and identified by one of three different detector systems. Use of a 2:1 peak height ratio typically produces a sequencing accuracy of 97.5% for the first 350 bases; a 3:1 peak height ratio improves accuracy to 99.5% for the first 400 bases. For these experiments, capillary electrophoresis is performed at an electric field of 200 V/cm; two to three hours are required to separate sequencing fragments up to 400 nucleotides in length. PMID- 1408804 TI - Effect of intermolecular triplex formation on the yield of cyclobutane photodimers in DNA. AB - We have studied the effect of intermolecular triplexes formation on the yield of cyclobutane photodimers in DNA. DNA duplex within the pyrimidine-purine pyrimidine triplex d(TC)nd(GA)nd(CT)n is protected from the formation of cyclobutane photodimers in the case of the stabilization of this triplex by acid pH, and in the case of supplementary stabilization by Mg2+ or Zn2+. We have studied pH-independent pyrimidine-purine-purine triplexes stabilized by bivalent cations. In such triplexes, the protection from the formation of [6-4] photodimers is observed, whereas the protection from cyclobutane dimer formation does not take place. The formation of the d(TC)nd(GA)nd(GA)n triplex leads to an inversion of the intensities of cyclobutane CT and TC photodimers. We observed a sharp decrease in photoreactivity with respect to cyclobutane dimers in the duplex tract d(C)18d(G)18 in the presence of Ba2+, Cd2+, Co2+, Mn2+, Zn2+ and Ni2+. The formation of the d(C)nd(G)nd(G)n triplex leads to 'antifootprinting', i.e. an increase in the yield of cyclobutane photodimers. PMID- 1408805 TI - The transcriptional start site for a human U6 small nuclear RNA gene is dictated by a compound promoter element consisting of the PSE and the TATA box. AB - Transcription of vertebrate U6 snRNA genes by RNA polymerase III requires two sequence elements in the proximal promoter region: the PSE (proximal sequence element, found in snRNA promoters transcribed by RNA polymerase II) and the TATA element (found in many mRNA promoters). The locations of the PSE and the TATA box are important determinants for transcriptional start site selection in their respective RNA polymerase II promoters. In vertebrate U6 genes the PSE and the TATA elements are located in approximately the same positions as in the polymerase II transcribed genes, but their respective roles in initiation site selection are unknown. We have analyzed the effects of spacing changes between the PSE and the TATA element, and between the two elements and the normal U6 start site on human U6 gene transcription. The spacing requirement between the two elements is highly stringent, implying a possible interaction between the factors that bind them. Our results discount the possibility that the location of either the PSE or the TATA element, by itself, dictates efficient selection of a transcriptional start site. Instead, we suggest that the two elements form a compound promoter element whose location dictates the start site of transcription from the human U6 gene promoter. PMID- 1408807 TI - Nucleotide sequence of a mouse cDNA encoding the non-histone chromosomal high mobility group protein-2 (HMG-2) PMID- 1408806 TI - The 66 kDa component of yeast SFI, stimulatory factor I, is hsp60. AB - DNA polymerase epsilon stimulatory factor I (SFI) has been shown to contain three peptides, p66, p37 and p13. Two of these components have been identified. The p66 gene was cloned by using a p66 antibody to screen a lambda gt11 library. A portion of the gene was sequenced and confirmed to encode p66 by the presence of protein sequence corresponding to that of p66 tryptic peptides. The gene was identified as HSP60 by a homology search of GenBank. Tryptic peptides of p37 were sequenced and identified as belonging to yeast translation initiation factor 4A by a homology search of PIR. The HSP60 gene maps to chromosome XII. PMID- 1408808 TI - Nucleotide sequence of the intron of the germline human kappa immunoglobulin gene connecting the J and C regions reveals a matrix association region (MAR) next to the enhancer. PMID- 1408809 TI - A common sequence motif among prokaryotic DNA primases. PMID- 1408810 TI - Activation of S1 nuclease at neutral pH. PMID- 1408811 TI - Efficient amplification of HIV half-genomes from tissue DNA. PMID- 1408812 TI - An improved thermal cycle for two-step PCR-based targeted mutagenesis. PMID- 1408814 TI - Double-stranded DNA segments can efficiently prime the amplification of human genomic DNA. PMID- 1408813 TI - A rapid method for determining the molecular weight of a protein bound to nucleic acid in a mobility shift assay. PMID- 1408816 TI - Alw26I, Eco31I and Esp3I--type IIs methyltransferases modifying cytosine and adenine in complementary strands of the target DNA. AB - The specificity of three DNA methyltransferases M.Alw26I, M.Eco31I and M.Esp3I, isolated from Acinetobacter Iwoffi RFL26, Escherichia coli RFL31 and Hafnia alvei RFL3+, respectively, was determined. All the enzymes methylate both strands of asymmetric recognition sites yielding m5C in the top-strand and m6A in the bottom strand, as below: 5'-GTm5CTC 5'-GGTm5CTC 5'-CGTm5CTC 3'-Cm6AGAG 3'-CCm6AGAG 3' GCm6AGAG (M.Alw26I) (M.Eco31I) (M.Esp3I) They are the first members of type IIs methyltransferases that modify different types of nucleotides in the recognition sequence. PMID- 1408817 TI - Nutritional regulation of nucleosomal structure at the chicken malic enzyme promoter in liver. AB - Transcription of the chicken malic enzyme gene in the liver is stimulated by feeding and inhibited by starvation. Concomitant with the increase in transcription caused by refeeding, chromatin structure around the transcription start site of the malic enzyme gene is modified in the liver. Digestion of chromatin in isolated nuclei with DNase I revealed four feeding-induced DNase I hypersensitive sites (-220, -170, -130 and -70 bp) near the malic enzyme promoter. Similarly, digestion of chromatin with restriction endonucleases detected enhanced cleavage within this region when birds were refed. Micrococcal nuclease detected the presence of nucleosomes over this region in the starved state, but not in the fed state. After food was withdrawn from fed birds, nucleosomes were reformed in this region within 6 h. The speed and magnitude of the changes in nucleosomal structure in this region suggest that they did not require DNA replication. PMID- 1408815 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1408818 TI - Site-specific cleavage of IGF-II mRNAs requires sequence elements from two distinct regions of the IGF-II gene. AB - The human insulin-like growth factor II (IGF-II) gene constitutes a complex transcriptional unit that contains nine exons and four promoters. Expression of the IGF-II gene yields a family of mRNAs that all encode prepro-IGF-II. In addition, a stable 1.8 kb RNA is formed that is derived from the 3' untranslated region of exon 9. Recently, we have shown that this RNA species arises by site specific endonucleolytic cleavage of IGF-II mRNAs and not by transcription from a separate promoter. In the present study we establish that two widely separated sequence elements of approximately 300 nucleotides, both located within exon 9, are required for this cleavage reaction. The first element encompasses about 200 nucleotides upstream and 100 nucleotides downstream of the cleavage site, while the second element is located within a region of 330 nucleotides about 2 kb upstream of the cleavage site. Interestingly, site-specific cleavage also occurred when a fragment from exon 9 of the IGF-II gene containing these two elements was inserted into the 3' untranslated part of the beta-globin gene. Apparently, the expressed hybrid beta-globin-IGF-II mRNA contains all the regulatory elements to confer site-specific endonucleolytic cleavage. PMID- 1408819 TI - Specificities of three tight-binding Lac repressors. AB - Tight binding mutants of Lac repressor exhibit complex repression phenomena. In this work, in vivo Lac operator binding of three such mutants of E. coli Lac repressor (X86: ser 61-leu, l12: pro 3-tyr and the double mutant l12X86: pro 3 tyr, ser 61-leu) was analyzed. Repression of beta-galactosidase synthesis controlled by ideal lac operator and its 27 symmetric operator variants containing each possible base-pair at each single half-operator position in the presence of the tight-binding Lac repressor mutants was determined. The average increase of repression with all operator variants was about 3 fold with the X86 mutant. It was about 4 fold with the l12 mutant and about 2 fold with the double mutant l12X86 as compared to wildtype Lac repressor. The X86 mutant showed the same increase of affinity to all operator variants, whereas the l12 and l12X86 mutants exhibited lower repression with some variants than with most others. These results suggest that the X86 mutant has gained no additional specificity. In contrast the l12 mutant and the l12X86 mutant exhibit a relaxed specificity for certain base pairs in positions 1 and 3 of lac operator. This suggests that the extreme N-terminus of Lac repressor may interact with the inner base-pairs in the minor groove. PMID- 1408820 TI - Identification of the CTAG-recognizing restriction-modification systems MthZI and MthFI from Methanobacterium thermoformicicum and characterization of the plasmid encoded mthZIM gene. AB - Two CTAG-recognizing restriction and modification (R/M) systems, designated MthZI and MthFI, were identified in the thermophilic archaeon Methanobacterium thermoformicicum strains Z-245 and FTF, respectively. Further analysis revealed that the methyltransferase (MTase) genes are plasmid-located in both strains. The plasmid pFZ1-encoded mthZIM gene of strain Z-245 was further characterized by subcloning and expression studies in Escherichia coli followed by nucleotide sequence analysis. The mthZIM gene is 1065 bp in size and may code for a protein of 355 amino acids (M(r) 42,476 Da). The deduced amino acid sequence of the M.MthZI enzyme shares substantial similarity with four distinct regions from several m4C- and m6A-MTases, and contains the TSPPY motif that is so far only found in m4C-MTases. Partially overlapping with the mthZIM gene and in reverse orientation, an additional ORF was identified with a size of 606 bp potentially coding for a protein of 202 amino acids (M(r) 23.710 Da). This ORF is suggested to encode the corresponding endonuclease R.MthZI. PMID- 1408821 TI - Nucleolin forms a specific complex with a fragment of the viral (minus) strand of minute virus of mice DNA. AB - Nucleolin, a major nucleolar protein, forms a specific complex with the genome (a single-stranded DNA molecule of minus polarity) of parvovirus MVMp in vitro. By means of South-western blotting experiments, we mapped the binding site to a 222 nucleotide motif within the non-structural transcription unit, referred to as NUBE (nucleolin-binding element). The specificity of the interaction was confirmed by competitive gel retardation assays. DNaseI and nuclease S1 probing showed that NUBE folds into a secondary structure, in agreement with a computer assisted conformational prediction. The whole NUBE may be necessary for the interaction with nucleolin, as suggested by the failure of NUBE subfragments to bind the protein and by the nuclease footprinting experiments. The present work extends the previously reported ability of nucleolin to form a specific complex with ribosomal RNA, to a defined DNA substrate. Considering the tropism of MVMp DNA replication for host cell nucleoli, these data raise the possibility that nucleolin may contribute to the regulation of the parvoviral life-cycle. PMID- 1408822 TI - A rapid chemiluminescent method for quantitation of human DNA. AB - A sensitive and simple method for the quantitation of human DNA is described. This method is based on probe hybridization to a human alpha satellite locus, D17Z1. The biotinylated probe is hybridized to sample DNA immobilized on nylon membrane. The subsequent binding of streptavidin-horseradish peroxidase to the bound probe allows for chemiluminescent detection using a luminol-based reagent and X-ray film. Less than 150 pg of human DNA can easily be detected with a 15 minute exposure. The entire procedure can be performed in 1.5 hours. Microgram quantities of nonhuman DNA have been tested and the results indicate very high specificity for human DNA. The data on film can be scanned into a computer and a commercially available program can be used to create a standard curve where DNA quantity is plotted against the mean density of each slot blot signal. The methods described can also be applied to the very sensitive determination of quantity and quality (size) of DNA on Southern blots. The high sensitivity of this quantitation method requires the consumption of only a fraction of sample for analysis. Determination of DNA quantity is necessary for RFLP and many PCR based tests where optimal results are obtained only with a relatively narrow range of DNA quantities. The specificity of this quantitation method for human DNA will be useful for the analysis of samples that may also contain bacterial or other non-human DNA, for example forensic evidence samples, ancient DNA samples, or clinical samples. PMID- 1408823 TI - Hydrolysis of oligoribonucleotides: influence of sequence and length. AB - The chemical stability of phosphodiester bonds of some oligoribonucleotides in the presence of a cofactor like polyvinylpyrolidine (PVP) is sequence dependent. It was found that pyrimidine-A (YA) and pyrimidine-C (YC) are especially susceptible to hydrolysis. The hydrolyzability of this same phosphodiester bond is dependent on its position in the oligomer. The presence of 3' and 5'-adjacent nucleotides enhances hydrolysis of the UA phosphodiester bond. The acceleration of the hydrolysis of UA by a 5'-adjacent nucleotide is not base dependent. However, a 3'-adjacent purine increases hydrolysis of a UA phosphodiester bond more than a 3'-pyrimidine. The presence of the exoamino group on the 3'-side base (on 6 and 4 position for adenosine and cytidine, respectively) of YA or YZ phosphodiester bond is required for hydrolysis. PMID- 1408824 TI - Nonenzymatic hydrolysis of oligoribonucleotides. AB - Selective cleavage of phosphodiester bonds in RNA is important in the processing of large RNA molecules. This paper reports specific cleavage at UA sequences in single stranded oligoribonucleotides as short as hexamers. The hydrolysis between U and A leaves a 2',3'-cyclic phosphate on the 5'-side and a 5'-hydroxyl group on the 3' side of the cleavage. The hydrolysis is promoted by a wide range of cofactors, including polymeric organic compounds such as polyvinylpyrrolydone (PVP) and by proteins. A variety of experiments suggests the cleavage is not due to contamination by ribonuclease. The rate of cleavage is a function of oligoribonucleotide, PVP and spermidine concentrations. Mg2+ is not required. The phenomenon described here can potentially provide a relatively simple way of coding chemical stability into single stranded RNA based on its sequence and structure. This process seems to be similar to that involved in post transcriptional degradation of mRNA. PMID- 1408825 TI - Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. AB - Methylated DNA in vertebrates is associated with transcriptional repression and inactive chromatin. Two activities have been identified, MeCP1 and MeCP2, which bind specifically to DNA containing methyl-CpG pairs. In this report we characterize MeCP2. We show that it is more abundant than MeCP1, is more tightly bound in the nucleus, and is distinguishable chromatographically. The two proteins share widespread expression in somatic mammalian cells, and barely detectable expression in early embryonic cells. DNAs containing thymidine which has a methyl group at position 5 are not ligands for the MeCPs. The possible role of MeCP2 in methylation-associated gene inactivation was tested in in vitro transcription extracts. Purified MeCP2 inhibited transcription from both methylated and nonmethylated DNA templates in vitro, probably due to the presence of nonspecific DNA binding domains within the protein. We hypothesise that MeCP2 normally binds methylated DNA in the context of chromatin, contributing to the long-term repression and nuclease-resistance of methyl-CpGs. PMID- 1408826 TI - Clathrin light chain B: gene structure and neuron-specific splicing. AB - The clathrin light chains are components of clathrin coated vesicles, structural constituents involved in endocytosis and membrane recycling. The clathrin light chain B (LCB) gene encodes two isoforms, termed LCB2 and LCB3, via an alternative RNA splicing mechanism. We have determined the structure of the rat clathrin light chain B gene. The gene consists of six exons that extend over 11.9 kb. The first four exons and the last exon are common to the LCB2 and LCB3 isoforms. The fifth exon, termed EN, is included in the mRNA in brain, giving rise to the brain specific form LCB2 but is excluded in other tissues, generating the LCB3 isoform. Primary rat neuronal cell cultures express predominantly the brain specific LCB2 isoform, whereas primary rat cultures of glia express only the LCB3 isoform, suggesting that expression of the brain-specific LCB2 form is limited to neurons. Further evidence for neuronal localization of the LCB2 form is provided using a teratocarcinoma cell line, P19, which can be induced by retinoic acid to express a neuronal phenotype, concomitant with the induction of the LCB2 form. In order to determine the sequences involved in alternative splice site selection, we constructed a minigene containing the alternative spliced exon EN and its flanking intron and exon sequences. This minigene reflects the splicing pattern of the endogenous gene upon transfection in HeLa cell and primary neuronal cell cultures, indicating that this region of the LCB gene contains all the necessary information for neuron-specific splicing. PMID- 1408827 TI - Modified DNA fragments activate NaeI cleavage of refractory DNA sites. AB - Endonuclease NaeI cleaves DNA using a two-site mechanism. The DNA-binding sites are nonidentical: they recognize different families of flanking sequences. A unique NaeI site that is resistant to cleavage resides in M13 double-stranded DNA. NaeI can be activated to cleave this site by small DNA fragments containing one or more NaeI sites. These activators are not practical for genetic engineering because unphosphorylated activators that are consumed during the cleavage of substrate give ends that may interfere with subsequent ligations. We show that a DNA fragment containing phosphorothioate linkages at the NaeI scissile bonds (S-activator) is not cleaved by NaeI, even though this S-activator binds to the substrate site. The S-activator activates NaeI to cleave M13 DNA under conditions that completely exhaust unsubstituted activator. These results demonstrate that activation is not coupled to cleavage of activator, that NaeI reverts to its inactive state soon after dissociation of the EA complex, and that S-activator makes for a nondepletable activator during prolonged incubations. PMID- 1408828 TI - DNA diversity among clinical isolates of Helicobacter pylori detected by PCR based RAPD fingerprinting. AB - The RAPD (or AP-PCR) DNA fingerprinting method was used to distinguish among clinical isolates of Helicobacter pylori, a bacterium whose long term carriage is associated with gastritis, peptic ulcers and gastric carcinomas. This method uses arbitrarily chosen oligonucleotides to prime DNA synthesis from genomic sites to which they are fortuitously matched, or almost matched. Most 10-nt primers with > or = 60% G + C yielded strain-specific arrays of up to 15 prominent fragments, as did most longer (> or = 17-nt) primers, whereas most 10-nt primers with 50% G+C did not. Each of 64 independent H. pylori isolates, 60 of which were from patients in the same hospital, was distinguishable with a single RAPD primer, which suggests a high level of DNA sequence diversity within this species. In contrast, isolates from initial and followup biopsies were indistinguishable in each of three cases tested. PMID- 1408829 TI - Adenovirus DNA replication facilitates binding of the MLTF/USF transcription factor to the viral major late promoter within infected cells. AB - The activity of the adenovirus major late promoter is substantially increased as the infection proceeds from the early to late phase. To gain insight into the regulation of this promoter, we analyzed protein-DNA interactions by in vivo DMS and DNasel footprinting during the course of adenovirus infection. Little or no protein interaction at promoter sequences was detected early (5 hr) after infection but strong interactions at the major late transcription factor (MLTF/USF) binding site and at the TATA box were evident late (12 hr) after infection. Comparison of in vivo and in vitro footprints revealed that the in vivo interaction late after infection results from binding of the cellular transcription factor MLTF/USF. Nuclear extracts prepared from uninfected cells as well as cells harvested at 5 and 12 hr after infection contained similar levels of MLTF/USF footprint activity, therefore the lack of a detectable interaction early after infection is not due to reduced levels of the factor early in the viral growth cycle. Viral DNA replication was required for MLTF/USF binding at the major late promoter. These results indicate that DNA replication participates in the regulation of adenovirus late gene expression by facilitating the binding of a transcription factor to the major late promoter. PMID- 1408830 TI - Synthesis of oligodeoxyribonucleotides containing degenerate bases and their use as primers in the polymerase chain reaction. AB - Heptadecaoligodeoxyribonucleotides containing one or more of the bases, 6H,8H-3,4 dihydropyrimido[4,5-c][1,2]oxazin-7-one (P), 2-amino-6-methoxyaminopurine (K), and hypoxanthine (I) and combinations of P with K and I have been synthesised on a DNA synthesiser. The stability of duplexes containing these basemodified oligomers with P/A, P/G, K/C and K/T; P/A, P/G, I/C, I/T and I/A, I/G, I/C, I/T base pairs were compared by measuring their melting transition (Tm) values. Oligomers containing both P and K and P and I were more stable than those with I alone or with mismatches. These oligomers together with one with a P base at the 3'-end were used as primers in polymerase chain reaction (PCR) experiments. They were all effective primers except one with I alone and a triple mismatch. Thus the use of the degenerate bases P and K in primer design is established. PMID- 1408831 TI - The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1. AB - Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis. PMID- 1408832 TI - Structural effect of donor DNA on the initiation of recombination for double strand break repair in human nuclear extracts. AB - The effect of the structure of donor DNA molecules on the initiation of recombination for double strand break repair in human nuclear extracts, was investigated here. A unique double strand break was introduced into M13 duplex derivatives by digestion with restriction enzymes. After coincubation of the cleaved DNA in human nuclear extracts, with a plasmid containing M13 sequences spanning the break, double strand break repair was estimated by the plating efficiency in JM109 (RecA1) bacteria. We first confirm that a short heterologous insert (8bp) close to the break on the recipient cleaved M13 DNA inhibits recombination with circular as well as with linear donor molecules. The results indicate that, with these substrates, recombination is initiated at the level of the break, requires uninterrupted homology on both sides of the break, and is associated with a decreasing gradient of gene conversion. When the heterologous insertion is located on the plasmid donor DNA, similar results are obtained with a circular donor DNA. In contrast, with a linear donor molecule, bearing the insert, homology requirements, in the region of the break in M13 DNA, are abolished. This last result suggests that recombination could be initiated at the extremities of the linear donor DNA. PMID- 1408834 TI - Differential ASF/SF2 activity in extracts from normal WI38 and transformed WI38VA13 cells. AB - The normal human fibroblast cell line WI38 and a transformed derivative, WI38VA13, differentially splice fibronectin pre-mRNA in vivo. As a first step to understand the molecular basis for this regulation of splicing, we examined the ability of WI38 and WI38VA13 nuclear extracts to splice model adenovirus and globin pre-mRNAs. Adenovirus RNA splicing was detected in WI38VA13 but not in WI38 extracts. Likewise, when supplemented with a HeLa post-nuclear supernatant (S100), human beta-globin RNA splicing was detected in WI38VA13 but not in WI38 extracts. The splicing defect in WI38 extracts was associated with a reduced ability to form splicing complexes and with a corresponding decrease in the interaction of U2 small nuclear ribonucleoprotein (snRNP) with the branchsite. These defects did not correlate with a decrease in 65 kD U2AF binding since equivalent U2AF level and activity were detected in WI38 and WI38VA13 extracts. Rather, WI38 extracts displayed reduced ASF/SF2 activity and contained a low level of 30 and 40 kD SR phosphoproteins. Moreover, addition of purified ASF/SF2 dramatically increased splicing complex formation in WI38 extracts. These results raise the possibility that variations in the level and activity of ASF/SF2 and other SR proteins play a role in the regulation of fibronectin splicing. PMID- 1408833 TI - The selective isolation of novel cDNAs encoded by the regions surrounding the human interleukin 4 and 5 genes. AB - We have developed modifications to direct cDNA selection that allow the rapid and reproducible isolation of low abundance cDNAs encoded by large genomic clones. Biotinylated, cloned genomic DNAs are hybridized in solution with amplifiable cDNAs. The genomic clones and attached cDNAs are captured on streptavidin coated magnetic beads, the cDNAs are eluted and amplified. We have applied this protocol to a 425kb YAC that contains the human IL4 and IL5 genes. After two cycles of enrichment twenty-four cDNAs were evaluated, all of which were homologous to the YAC. DNA sequencing revealed that nine cDNAs were 100% homologous to the interferon regulatory factor 1 (IRF1) gene. Six clones were 70% homologous to the murine P600 gene, which is coexpressed with IL4 and IL5 in mouse Th2 cells. The nine remaining clones were unique within the sequence databases and were non redundant. All of the selected cDNAs were initially present at very low abundance and were enriched by as much as 100,000-fold in two cycles of enrichment. This modified selection technique should be readily applicable to the isolation of many candidate disease loci as well as the derivation of detailed transcription maps across large genomic regions. PMID- 1408835 TI - The estimation of distances between specific backbone-labeled sites in DNA using fluorescence resonance energy transfer. AB - A series DNA helices of twenty-four base pairs has been prepared for the study of fluorescence resonance energy transfer. Each of the DNA helices contains two phosphorothioate diesters (one in each strand) at pre-selected sites for introduction of the desired donor and acceptor fluorophores. The phosphorothioate containing oligodeoxynucleotides have been prepared as pure Rp or Sp derivatives or as deastereomeric mixtures. Fluorescein and eosin are employed as the respective donor and acceptor fluorophores. A series of donor-acceptor pairs was generated by labeling of the appropriate phosphorothioate diester with the desired fluorophore and annealing the two complementary DNA strands (one containing the acceptor and one containing the donor fluorophore) to form the double-stranded helix. The 24-mer helices containing two covalently attached fluorophores exhibited some thermal destabilization and the extent of this destabilization was dependent upon the stereochemical orientation of the fluorophore. The Sp derivatives direct the fluorophore out, away from the the DNA helix, while the Rp derivatives direct the fluorophore toward the major groove. As expected, the Sp labeled duplexes were more stable than the corresponding Rp labeled sequences. However, all of the duplex structures formed were stable under the conditions used to measure energy transfer. Energy transfer could be observed with these complexes from the quenching of the donor fluorescence in the presence of the acceptor fluorophore. Using Forster's theories, distances separating the fluorophores could be calculated that were generally in reasonable agreement with the distances expected in an idealized B-form DNA helix. However anomalous results were obtained for one donor/acceptor pair where the expected distance was less than 20 A. Fluorescence anisotropy values determined in solutions of varying viscosity were quite high suggesting that the fluorophores did not experience complete freedom of movement when attached to the DNA helix. PMID- 1408837 TI - The nucleotide sequence of the L10 equivalent ribosomal protein gene of Streptomyces antibioticus. PMID- 1408836 TI - Yeast RNC1 encodes a chimeric protein, RhoNUC, with a human rho motif and deoxyribonuclease activity. AB - The yeast Saccharomyces cerevisiae contains an endoexonuclease yNucR that has been implicated in both recombination and repair. We describe the isolation and characterization of the corresponding gene. Within the predicted N-terminal half of the protein there is extensive homology (approximately 50%) with human rho genes, which are related to the ras oncogene, particularly in the proposed GTP binding region. The C-terminal region, which is related to the Escherichia coli recC protein, presumably encodes the endoexonuclease activity. The yNucR may thus represent a new class of GTP-binding proteins. Because of the chimeric nature of the polypeptide, this protein is renamed RhoNUC (rather than the original yNucR) and the gene is RNC1 for Rho-associated-NuClease. Over expression of the gene leads to altered cell growth and nuclear morphology. We propose that the gene plays an important role in cell development as well as DNA repair/recombination. PMID- 1408838 TI - Nucleotide sequence of U5 RNA from a green alga, Chlamydomonas reinhardtii. PMID- 1408840 TI - Phylogenetic position of Trimorphomyces papilionaceus based on 5S rRNA sequence. PMID- 1408839 TI - Nucleotide sequence of the genes encoding the subunits H, B, A' and A'' of the DNA-dependent RNA polymerase and the initiator tRNA from Thermoplasma acidophilum. PMID- 1408841 TI - Tobacco cDNA encoding the ribosomal protein S6. PMID- 1408842 TI - Similarity between subunit 8 of yeast RNA polymerase II (RPB8) and the second largest subunits of eukaryotic RNA polymerases. PMID- 1408843 TI - Nucleotide sequence of a nuc gene encoding the thermonuclease of Staphylococcus intermedius. PMID- 1408844 TI - Efficient retroviral-mediated gene transfer into human B lymphoblastoid cells expressing mouse ecotropic viral receptor. PMID- 1408845 TI - Sex typing of Aratinga parrots using the human minisatellite probe 33.15. PMID- 1408846 TI - A simple method for amplification of DNA from paraffin-embedded tissues. PMID- 1408847 TI - A coupled Southwestern--DNase I footprinting assay. PMID- 1408848 TI - A simple in vitro site directed mutagenesis of concatamerized cDNA by inverse polymerase chain reaction. PMID- 1408849 TI - A simple and rapid method for detection of apoptosis in human cells. PMID- 1408851 TI - Turning toward a preferred future. PMID- 1408852 TI - Environmental compatibility: accepting the challenge. PMID- 1408850 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1408853 TI - Issues concerning women and AIDS: sexuality. PMID- 1408854 TI - Addressing infrequent cancer screening among women. AB - National health policies must be revised to support basic health services for all Americans, a breadth of cost-effective health practitioners, and a system that provides comprehensive, coordinated care in decentralized locations. State and local advocacy groups should increase consumers and policy-makers awareness about inadequate cancer screening. Educational institutions should address cancer prevention for practitioners in training. Practice institutions should employ nurses and nurse practitioners more effectively, as well as institute computerized feed-back and reminder systems. More rigorous research on the effect of educational messages on client beliefs, affect, and screening behavior are needed to guide interventions for cancer control. PMID- 1408855 TI - AAN working paper. Wellness and health promotion of the elderly. AB - One of the missions of the American Academy of Nursing is to formulate strategies for health policy. To arrive at these strategies, Academy members share their thoughts, knowledge, and imagination in working groups at Academy meetings. The Expert Panel on Older Adults, one of these working groups, asked for interested members to formulate a policy paper on wellness and health promotion of the elderly for presentation at the AAN meeting in Los Angeles last October. This was done, and AAN members at that meeting shared their views on the paper. Now, this draft is being published here to invite all Nursing Outlook readers to review and comment on the policy recommendations that have been formulated. We encourage feedback so your ideas can be considered in the development of the paper. The paper will be submitted for approval to the AAN Committee on Health Policy Reform. PMID- 1408856 TI - Students in transition: services for retention and outplacement. PMID- 1408857 TI - Nursing practicum: empowering strategies. AB - The concepts embodied by the practicum are best summarized by students themselves: "Through practicum, I have become more independent and my clinical instructor guided me to independence. I have grown in my own knowledge, skills, performance and confidence in myself." "This course was wonderful--it allows for independence in the clinical area and choice related to the area of study. It improved and developed my self-motivation." "Practicum promotes independence with guidance from faculty and preceptors when needed. The independence promotes decision-making by the student. The course pulls together a lot, if not all, the things taught in school." "I really liked writing my own learning contact and the opportunity to build confidence in my nursing practice." PMID- 1408858 TI - A call for educational reform: Colorado nursing doctorate model as exemplar. PMID- 1408859 TI - More than skin deep. PMID- 1408860 TI - Measurement of safe sex behavior in adolescents and young adults. AB - The aim of this project was to develop an instrument to measure use of safe sex practices among adolescents and to conduct initial evaluation of the psychometric properties of the instrument. The Safe Sex Behavior Questionnaire (SSBQ) was designed to measure the frequency of use of safe sex practices and was assessed for content validity, reliability, and construct validity through a series of tests. The content validity index computed for the SSBQ was 98%. Initial reliability computed for sums of items of the total scale was .82 among 89 college freshmen. Using a second sample of 531 subjects, the SSBQ was factor analyzed separately for males and females and five similar factors emerged for each gender. Reliability coefficients for sums of salient items for each factor ranged from .52 to .85. Using a third sample of 174 subjects, construct validity was assessed by correlating the SSBQ with measures of general assertiveness and general risk-taking. The resulting correlations were appreciable and in the predicted directions, thus providing support for the construct validity of the instrument. PMID- 1408861 TI - A randomized trial of a health care program for first-time adolescent mothers and their infants. AB - To test the effectiveness of a special health care program for adolescent mothers (17 years old or younger) and their infants, 243 mother-infant pairs were randomly assigned to one of two groups. All of the mothers were unwed, on Medicaid, and black. The control group received routine well-baby care. The experimental group received routine care and services that included rigorous follow-up, discussions with the mother about her plans for return to school and use of family planning methods, and extra health teaching. The dropout rate in the experimental group (60%) was significantly less after 18 months than the control group (82%). In spite of the high dropout rate, 91% of the mothers were located for the 18 month follow-up interview. The repeat pregnancy rate in the experimental group was 12% after 18 months, and 28% in the control group. There was no significant difference in the percentage returning to school. After 12 months, the infants in the experimental group were more likely to be fully immunized (33%) than the infants in the control group (18%). Mothers in the special care program who continued to attend clinic used the emergency room less than the mothers who continued to attend in the control group. These results suggest that a comprehensive health care program is one way to bring about better outcomes for both adolescent mothers and their infants. PMID- 1408862 TI - Determinants of career attainments of doctorates in nursing. AB - The career attainments of graduates of doctoral programs in nursing during two academic career stages after the doctorate were examined. Educational associations and work experiences were the most important determinants of postdoctoral career attainments. The quality of the doctoral program attended and predoctoral work experiences significantly influenced initial institutional quality, which in turn influenced current institutional quality. The current institutional quality, then, had direct effects on current attainments in the areas of professorial rank, publication productivity, and income. Graduate school quality was the most important factor in first institutional quality, as it tracked faculty into certain strata of the higher educational hierarchy. Consistent with the academic stratification system in higher education, those in high quality programs attained lower professorial ranks but higher publication productivity and higher recognition than those who gained employment in unranked schools. PMID- 1408863 TI - Preventability of infant mortality in a rural community. AB - Preventability of infant mortality in a rural southern county was examined with a Delphi technique using case summaries of infant deaths during a selected four year period. The first two rounds were aimed at developing a consensus of panelists' opinions about problems leading to the high infant mortality rate in the study area. From these opinions, an Infant Mortality Preventability Decision Tree and a Problem List was developed. Panelists used these in Rounds III and IV to evaluate the case summaries. There were significant differences in the preventability ratings between physicians and nurses, indicating the importance of assessing individuals' philosophies of preventability when working with an interdisciplinary team of health care providers. PMID- 1408864 TI - Parental division of infant care: contextual influences and infant characteristics. AB - The purpose of this study was to explore the relationship of maternal employment to division of parental infant caregiving and whether infant characteristics predicted maternal and paternal caregiving during the first year. Subjects were 351 families with healthy infants from normal pregnancies. Measures included a newborn and 1-month Brazelton Neonatal Behavioral Assessment, Child Care Activities Scale at 1, 6, and 12 months, Bates Infant Characteristics Questionnaire at 6 and 12 months, and selected demographics. Mothers provided the majority of infant care though fathers' proportion increased with employment of mothers. Controlling for demographics, infant characteristics were infrequent predictors of maternal caregiving and predicted a small amount of paternal caregiving variance. PMID- 1408865 TI - Psychosocial variables, race, and intention to seek care for breast cancer symptoms. AB - This study was designed to assess whether the influences of affect, utility, norm, and habit on intention to seek care promptly for a breast cancer symptom were conditional upon race. Ninety-six participants (68% Caucasian and 32% African American) in community settings completed measures of psychosocial, demographic, and clinical variables, and intention to seek care promptly for a breast lump. Controlling for education, financial coverage for health care, and family history of breast disease, the interactions of both utility and norm with race significantly explained intention. The positive influence of utility on intention was stronger among Caucasians than African Americans, but significant among both groups. The positive influence of social norm on intention was significant for Caucasians, but not for African Americans. PMID- 1408866 TI - Relaxation to reduce dyspnea and anxiety in COPD patients. AB - The purpose of this study was to test the effectiveness of a taped relaxation message in reducing dyspnea and anxiety in chronic obstructive pulmonary disease (COPD) patients. Twenty-six adult COPD patients with dyspnea were randomly assigned to two groups. The treatment group was taught relaxation using a prerecorded tape while the control group was instructed to sit quietly. Skin temperature, heart rate, and respiratory rate were recorded for all subjects during a total of four weekly sessions. Anxiety, dyspnea, and airway obstruction were measured at the beginning and end of the study. The relaxation group achieved the preset relaxation criteria. Dyspnea, anxiety, and airway obstruction were reduced in the relaxation group while the control group remained the same or became worse. PMID- 1408867 TI - The role of Nursing Research Committees. PMID- 1408868 TI - Doling out misery. PMID- 1408870 TI - Drink drive. PMID- 1408869 TI - Testing times. PMID- 1408871 TI - Brain drain. PMID- 1408872 TI - Women's business. PMID- 1408873 TI - Tales of travail. PMID- 1408874 TI - Advice to take home. PMID- 1408875 TI - Improving community services. PMID- 1408876 TI - Powerless to manage? PMID- 1408877 TI - Things that go bump. PMID- 1408878 TI - Order, order! PMID- 1408879 TI - Rediscovering refuge. PMID- 1408881 TI - Developing roles. PMID- 1408880 TI - Barriers to learning. PMID- 1408882 TI - Someone to turn to. PMID- 1408883 TI - Input on outcomes. PMID- 1408884 TI - The impact of mastectomy. PMID- 1408885 TI - How nurses see their 'caring' role. PMID- 1408886 TI - Cancer--the dual approach. PMID- 1408887 TI - Holistic power. PMID- 1408888 TI - Management module. M5: Quality in care. Part (i): What is quality? PMID- 1408889 TI - Risky complacency. PMID- 1408890 TI - Morale questions. PMID- 1408892 TI - Added difficulties. PMID- 1408891 TI - The numbers game. PMID- 1408893 TI - Women in charge. PMID- 1408894 TI - Who draws the line? PMID- 1408895 TI - Help on the streets. PMID- 1408896 TI - Are you sitting comfortably? PMID- 1408897 TI - Education--critical and constructive. PMID- 1408898 TI - The history man. Interview by Daloni Carlisle. PMID- 1408899 TI - Exporting excellence. PMID- 1408900 TI - The baby blues club. PMID- 1408901 TI - Misery in Munich. Nursing abroad. PMID- 1408902 TI - Operations explained. Patient information. PMID- 1408903 TI - Hazards of N20 exposure. PMID- 1408904 TI - Don't sack staff with HIV, says UKCC. PMID- 1408905 TI - Mrs. Green's decline. PMID- 1408906 TI - Pressure relief--stand by your beds. PMID- 1408907 TI - Pressure relief--supporting evidence. PMID- 1408908 TI - Management module. M5: Quality in care. Part (ii): The individual practitioner. PMID- 1408909 TI - Midwives' extended role--not to serve junior doctors. PMID- 1408911 TI - Misused authority. PMID- 1408910 TI - Licence off? PMID- 1408912 TI - Russian roulette. PMID- 1408913 TI - Force for the future. PMID- 1408914 TI - Body politic--Virginia territory. PMID- 1408915 TI - Education--qualified to talk. Project 2000. PMID- 1408916 TI - Education--teething trouble. Project 2000. PMID- 1408917 TI - Education--mixed feelings. Project 2000. PMID- 1408918 TI - The white approach--learning disabilities. PMID- 1408919 TI - Comfort of strangers--care study. PMID- 1408920 TI - A questionable treatment. PMID- 1408921 TI - Education--the importance of practice. PMID- 1408922 TI - How much does it hurt? PMID- 1408923 TI - Breaking the silence. PMID- 1408924 TI - Swazi safari. PMID- 1408925 TI - Management module. M5: Quality in care. Part (iv): Nursing audit. PMID- 1408926 TI - Caring centre questioned. PMID- 1408928 TI - Clinical grading--hidden extras. PMID- 1408927 TI - Clinical grading--upgraded or degraded? PMID- 1408929 TI - Clinical grading--end of the road. PMID- 1408930 TI - Money isn't everything. PMID- 1408932 TI - Mind your back. Handle with care. PMID- 1408931 TI - A milestone in AIDS care. PMID- 1408933 TI - Tough decisions. PMID- 1408934 TI - Fit for what? PMID- 1408935 TI - Alcohol misconceptions. PMID- 1408936 TI - Making a break. PMID- 1408937 TI - Community Care Act. Information gap. PMID- 1408938 TI - Education--an adult approach. PMID- 1408939 TI - People--special mixture. Interview by Thelma Agnew. PMID- 1408940 TI - Systems of life. The nervous system. 1. PMID- 1408941 TI - Stress in dealing with cardiac arrests. PMID- 1408942 TI - Catheter confusion. PMID- 1408943 TI - Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. AB - Approximately 200 studies that examined the relationship between fruit and vegetable intake and cancers of the lung, colon, breast, cervix, esophagus, oral cavity, stomach, bladder, pancreas, and ovary are reviewed. A statistically significant protective effect of fruit and vegetable consumption was found in 128 of 156 dietary studies in which results were expressed in terms of relative risk. For most cancer sites, persons with low fruit and vegetable intake (at least the lower one-fourth of the population) experience about twice the risk of cancer compared with those with high intake, even after control for potentially confounding factors. For lung cancer, significant protection was found in 24 of 25 studies after control for smoking in most instances. Fruits, in particular, were significantly protective in cancers of the esophagus, oral cavity, and larynx, for which 28 of 29 studies were significant. Strong evidence of a protective effect of fruit and vegetable consumption was seen in cancers of the pancreas and stomach (26 of 30 studies), as well as in colorectal and bladder cancers (23 of 38 studies). For cancers of the cervix, ovary, and endometrium, a significant protective effect was shown in 11 of 13 studies, and for breast cancer a protective effect was found to be strong and consistent in a meta analysis. It would appear that major public health benefits could be achieved by substantially increasing consumption of these foods. PMID- 1408944 TI - Vitamin supplement use and risk for oral and esophageal cancer. AB - In a hospital-based case-control study, 290 oral cancer cases and 133 esophageal cancer cases were queried as to smoking status, alcohol consumption, and dietary exposures, including vitamin supplement history. Among oral cancer cases, vitamin E use appeared to exert a protective effect. Vitamins C and E had protective effects among esophageal cancer cases. When stratified by smoking status, the protective effect of vitamin C use in esophageal cancer was significant only among current smokers, as was vitamin B use. A reduced risk of oral cancer was correlated with multivitamin use and increasing vegetable consumption, as was vegetable/fruit consumption and vitamin C supplementation. Among esophageal cancer cases, increasing meat consumption and vitamin C use were associated with a significantly reduced cancer risk. PMID- 1408945 TI - The role of dietary phytosterols in colon carcinogenesis. AB - Epidemiological and experimental studies have shown that increased intake of plant foods and decreased meat consumption are correlated with a decreased risk for colon cancer. Many components of plant foods are suggested to mitigate colon carcinogenesis, including vitamins, minerals, and dietary fiber. Phytosterols are a common component of plant foods consumed in relatively large quantities by vegetarians, who are at lower risk for colon cancer development than individuals on a Western diet low in phytosterols. In addition, phytosterols have been shown experimentally to inhibit colon cancer development. Dietary cholesterol, although structurally similar to the phytosterols, is correlated etiologically to the incidence of colon cancer, with changes in serum cholesterol levels and fecal bile acid profiles suggested to increase susceptibility to colon tumorigenesis. The objective of this paper is to discuss the effect of dietary phytosterols on cholesterol and bile acid metabolism and how these effects may lead to a decreased risk for colon cancer development. PMID- 1408946 TI - Stability of fusarin C: effects of the normal cooking procedure used in China and pH. AB - Fusarin C (FC) is a naturally occurring mutagen found on Fusarium moniliforme contaminated corn. In Linxian, China, an area of exceptionally high incidence of esophageal cancer, the milled corn is made into small cakes called wotou, which are steamed. It has been suggested that FC may play a role in the etiology of esophageal cancer, but this has been questioned, in part, because of the thermal instability of FC. We therefore measured the effects of temperature on FC stability, mimicking the cooking process. FC was extracted from the wotou and quantitated by both reverse-phase high-performance liquid chromatography and the Ames assay. After wotou were steamed for 30 minutes, 11% and 3% of the initial FC remained, as detected by the two assays, respectively. The milled corn, when moistened with water, had a pH of 6.1, which was lowered to 5.3 when it was inoculated with F. moniliforme and cultured for three weeks. Pickled vegetables are sometimes added to the wotou, which further reduces the pH. To determine the effects of pH on FC, it was heated in solution, with the pH varied between 4 and 8. Its stability was very pH dependent, decomposing more rapidly as the pH increased. Because ingested FC would also be subjected to the low pH of the stomach, it was treated for 30 minutes at 37 degrees C and pH values ranging from 1.0 to 7.0. FC was stable (less than 15% decomposition) under these conditions. If FC is a significant health threat, it could most easily be destroyed by cooking at slightly basic pH values. PMID- 1408947 TI - Effect of dietary butylated hydroxytoluene on nuclear envelope cytochrome P-450 during the initiation and promotion stages of hepatocarcinogenesis. AB - The anticarcinogenic effect of the dietary antioxidant butylated hydroxytoluene (BHT) correlates with a preservation of nuclear envelope (NE) cytochrome P-450 in rats undergoing chemically induced hepatocarcinogenesis. This effect of BHT on NE cytochrome P-450 was observed during both the initiation and the promotion stages of hepatocarcinogenesis. Complex interactions between the two different mechanisms of action of BHT (i.e., enzyme induction and antioxidant activity) may account for some of the differences between the patterns of response to BHT observed during initiation and promotion. PMID- 1408948 TI - (-)-Epigallocatechin-3-gallate in Camellia sinensis leaves from Himalayan region of Sikkim: inhibitory effects against biochemical events and tumor initiation in Sencar mouse skin. AB - Recently, we and others showed that the components of green tea may be useful cancer chemopreventive agents. It has been suggested that (-)-epigallocatechin-3 gallate (EGCG), the major constituent in green tea, may possess antitumor promoting and/or anticarcinogenic effects in rodent tumor bioassay systems. During the chemical analysis of various green tea products, we found a traditionally preserved preparation of green tea used by tribes in the Himalayan region of Sikkim, India that was rich in EGCG. EGCG was isolated from this tea product, and its inhibitory effects were evaluated against the binding of topically applied 3H-labeled polycyclic aromatic hydrocarbons (PAHs) to epidermal DNA and 12-O-tetradecanoylphorbol-13-acetate (TPA) caused induction of epidermal ornithine decarboxylase (ODC) activity in Sencar mice, the short-term markers of tumor initiation and tumor promotion, respectively. Preapplication of EGCG resulted in significant inhibition (p less than 0.05) in the binding of [3H]PAH to epidermal DNA. Similarly, the topical application of EGCG resulted in significant inhibition (p less than 0.005) in TPA-caused induction of epidermal ODC activity. In further studies, we assessed the anti-skin tumor-initiating effect of EGCG in Sencar mice in an initiation-promotion protocol. The application of EGCG before challenge with 7,12-dimethylbenz[a]anthracene as tumor initiator resulted in significant reduction both in percentage of mice with tumors and number of tumors per mouse compared with a non-EGCG-pretreated group of animals. The results of the present study suggest that the green tea preparation from Sikkim may be a good source for the isolation of EGCG and that this compound may have significant potential as a cancer chemopreventive agent. PMID- 1408949 TI - Esophageal cancer and diet--a case-control study. AB - It has been estimated that approximately 40% of human cancers may be associated with dietary factors. The relationship is more significant in esophageal cancers. Case-control studies involving 35 subjects of early-diagnosed esophageal cancers showed low mean blood levels of retinol, zinc (p less than 0.001), folic acid (p less than 0.01), and albumin (p less than 0.05). Relative risk was significantly higher for low levels of retinol and zinc. Diet, in general, in both groups reflected poor intake of several nutrients. PMID- 1408950 TI - Codependency: characteristics, risks, progression, and strategies for healing. AB - Codependency and caring are issues concerning nurses practicing in the 1990s. Questions about "caring" and "caring too much" at one's own expense are examined. Characteristics, roles, and risk factors for codependency are identified. Strategies for healing are suggested for nurses who "care too much." PMID- 1408951 TI - Impact of a growing elderly population on nursing. AB - Medical advances have promoted longer, healthier lives with fewer diseases and more treatable illnesses for humans. Long-term care and chronic illnesses are becoming more common, increasing the need for nursing care of a growing elderly population. Nurses in all areas of specialization must be prepared to face these challenges and provide health care in an ethical manner. PMID- 1408952 TI - Differences in patient rating of care provided by BSN and ADN students. AB - Nursing has discussed widely and with fervor the level of education required to provide quality nursing care for clients. No clear consensus has developed but studies tend to show that especially in the hospital setting, baccalaureate (BSN) and associate degree (ADN) nurses initially practice at a similar level. No studies identified compared patient ratings of BSN and ADN nurses. In this study ratings of care provided by BSN and ADN students were compared. Patients, students and instructors rated the student sample using Watson's Patient Satisfaction Rating Scale. Using Pearson correlations and t-tests, the overall satisfaction with care was assessed as "very positive" by patients, faculty and students alike. A significant correlation was found between faculty and patient ratings. Results support earlier findings and demonstrate similarities rather than differences in care provided by the two levels of students. Implications for nursing education and practice are discussed. PMID- 1408953 TI - Said another way. An ethical issue for a profession for all seasons. AB - Often the spoken word does not lend itself to written record. Sometimes, however, the message is such that spoken or written, the value of the statement is such that we wish to revisit it often. My goal in this article is to get nurses to reflect on issues that confront us daily and give us the opportunity to return for further reflection as we mature through the seasons of our own professional growth. PMID- 1408954 TI - Leadership dimensions in a human context. PMID- 1408955 TI - The last word. The "parental role instant replay" theory of nursing leadership. PMID- 1408956 TI - Willa Cather and the spirit of nursing. AB - Willa Cather, believed to be one of America's first feminist novelists, wrote of strong, Nebraskan women who, at the start of the Industrial Age, struggled to maintain their basic values as pioneers in the face of oppression. Similarly, many nurses today fight to retain their basic values as nurses in the face of oppression from the dominant medical culture. The values shared by Cather's pioneers and some nurses of today include utilizing a woman-identified perspective, achieving power through intimacy, and encompassing multiple ways of knowing. The journey of Cather and her characters is discussed as a model for fighting oppression by maintaining the core values of one's profession--be it as nurses or as pioneers. PMID- 1408957 TI - Being "in style". PMID- 1408958 TI - Cisplatin overdosage. PMID- 1408959 TI - Coping strategies of family caregivers in hospice homecare. AB - Although stresses associated with family caregiving during illness have been well documented, little attention has been focused on how families cope with hospice home care of a relative with advanced cancer. A longitudinal, qualitative study examined the experiences of hospice caregiving families. This article focuses on coping strategies identified by hospice families caring for their dying relative at home. Semistructured interviews and observations were conducted with 14 individuals from 10 families. Fifty-five interviews were audiotaped and transcribed. Constant comparative analysis was used to search inductively for recurrent themes. Specific coping strategies were used with each of the three areas of stress identified by families. "Windows of time," social comparison, cognitive reformulation, and avoidance were used to cope with the overall caregiving experience. "Taking one day at a time" helped to manage uncertainty. Acceptance and rationalization helped families to deal with changes in a relative's mental status. Social support was used with all three areas of stress. Identifying effective coping strategies that families are using directs the development, testing, and implementation of nursing interventions that enhance coping of hospice caregiving families. PMID- 1408960 TI - Cutaneous toxicity associated with high-dose cytosine arabinoside. AB - High-dose cytosine arabinoside (HDAC) is used to treat adults with acute and chronic leukemia and non-Hodgkin's lymphoma. Although HDAC is associated with various toxicities, cutaneous toxicity in particular leads to alterations in comfort, interference with daily living activities, and increased risk of infection. The incidence of cutaneous toxicity ranges from 3%-72%. A review of the literature revealed a variety of terms describing this toxicity, which begins as erythema and progresses to painful swelling, bullae formation, and desquamation. The etiology is unclear, and the severity is related to the number of consecutive doses. Interventions specific to prevention and treatment of this toxicity were found to be minimal, with no interventions scientifically examined. The challenge for nurses is to explore measures that will minimize the complications, treat the manifestations, and document the impact of these problems on quality of life. PMID- 1408961 TI - Appraisal of illness, symptom distress, self-care burden, and mood states in patients receiving chemotherapy for initial and recurrent cancer. AB - Cancer recurrence may present unique stressors for patients receiving chemotherapy. The objectives of this exploratory study were to (1) describe perceptions of symptom distress, self-care burden, appraisal of illness, and mood in patients undergoing chemotherapy, (2) identify differences in these perceptions according to stage of illness (new versus recurrent cancer), and (3) test a theoretical model of the mediating effects of appraisal. Subjects completed a modified Symptom Distress Scale, the Self-Care Burden Scale, the Family Hardiness Index, the Appraisal of Illness Scale, the short form of the Profile of Mood States, and a self-report form that included personal and illness characteristics and questions about the subjects' current situation. The 60 subjects were outpatients being treated for initial cancer (n = 28) or recurrent cancer (n = 32). Those with recurrence had higher symptom distress and health deviation self-care burden scores and more stressful appraisals; mood scores were low and did not differ between groups. Appraisal, symptom distress, and perceived seriousness predicted 36% of variance in affective mood, with appraisal partially mediating the effects of symptom distress. Somatic mood (36%) was best predicted by symptom distress and universal self-care burden (USCB). Economic status, symptom distress, and recurrence status predicted 49% of appraisal variance. Symptom distress was predicted best by recurrence and symptom control; USCB was predicted best by economic status and perceived dependency. Results suggest the need for different nursing interventions for the two groups. Further model testing is recommended. PMID- 1408963 TI - Developing the oncology nurse from novice to expert. PMID- 1408962 TI - Malignant pericardial effusions: pathophysiology and clinical correlates. AB - Cardiac tamponade resulting from malignant pericardial effusions is a life threatening oncologic emergency. As many as 21% of all patients with cancer may be at risk for this complication. A malignant effusion often signifies progressing disease, creating stress and anxiety for patients and their families. By understanding the pathophysiology and pertinent risk factors, the nurse may identify an effusion before it progresses to cardiac tamponade. The goal of management is removal of fluid, restoration of hemodynamic functioning, and prevention of fluid reaccumulation. Emotional support and reassurance, as well as accurate information regarding the disease and treatment, also are critical in assisting patients to adapt to these changes in disease status. PMID- 1408964 TI - Undergraduate preparation of the oncology nurse. AB - Determining appropriate cancer-related content for undergraduate nursing curricula requires careful consideration of content that is needed versus content that is desired for the nurse generalist. Studies have indicated a wide variety of topics and time allotment for this content among schools of nursing. Innovative strategies using games, computers, preceptors, and elective courses have allowed schools of nursing to include more comprehensive coverage of oncology-related topics. Issues concerning clinical oncology nursing opportunities for undergraduate studies still need to be clarified. Undergraduate students must be afforded the legitimacy of their status as novices in nursing and in the specialty of oncology. Didactic and clinical experiences should result in the knowledge and skills needed to develop professionally from novice to expert. PMID- 1408965 TI - Continuing education for oncology nurses. AB - Continuing education plays a key role in the development of the expert oncology nurse. It also is the primary way to help maintain and expand the nurse's expertise. This paper uses the nursing process as the framework for discussion of the development of continuing education activities. Assessing learners' needs is necessary for the development of programs that are learner responsive. Program planning is a multistep process that includes determining priorities, purposes and objectives, instructional methods, resources, budget, and evaluation criteria. A wide range of instructional methods can be considered for program implementation. Evaluation may be conducted at several levels of program development and outcome. Each of these areas is an important component in the success of program development. PMID- 1408967 TI - Ocular side effects of chemotherapy: nursing management. AB - Ocular side effects may be unfamiliar to oncology nurses but are important because of their potentially devastating effects on vision. Presently, more than 20 chemotherapy agents have been reported to cause eye toxicities. Chemotherapy induced ocular side effects can be manifested on a range of minor, transient irritation to irreversible, complete blindness. This article reviews these ocular complications, their causative agents, their effect on eye structures and function, and nursing management. Oncology nurses can play a vital role in the identification of symptoms and in the management of these eye complications. PMID- 1408966 TI - Characteristics of the expert oncology nurse. AB - Oncology nursing is a specialty that continuously incorporates new technologic advances into everyday practice. These advances, coupled with an increasing acuity level of the patient with cancer, generate a demand for excellence. The successful development of the expert oncology nurse will be imperative in meeting these challenges. This paper provides a practical framework for examining expertise and describes characteristics of the expert oncology nurse. PMID- 1408968 TI - Humor brings a new perspective. PMID- 1408969 TI - Chemoprevention research increases. PMID- 1408970 TI - Implants administered without pain to patient. PMID- 1408971 TI - Word-search exercise teaches and challenges nurses. PMID- 1408972 TI - Cancer resources in the United States. PMID- 1408973 TI - Human bites in children. AB - Human bites are common during childhood and usually result from fights or aggressive play with another child. Bites may present as indentation marks, scratches, abrasions, contusions, or lacerations. Most human bite wounds are sustained on the upper extremities, followed by the face and neck, the trunk, and the lower extremities. Infection is the most common complication. Cultures of an infected bite wound yield an average of five microorganisms. This article reviews the current recommendations on the management of human bite wounds in children. PMID- 1408974 TI - Follow-up of patients with occult bacteremia in pediatric emergency departments. AB - Blood cultures are frequently obtained in pediatric emergency departments (EDs) from febrile young children at risk for bacteremia and subsequent development of serious bacterial infections. This study of 105 children with occult bacteremia treated in two large urban pediatric EDs describes the follow-up of these patients and the impact that positive blood culture results have on the detection of serious illness. Seventy-seven percent of patients had a follow-up visit in the ED, 8% had follow-up by telephone alone, and 15% were not contacted. Of the patients who returned to the ED, 49% did so because they were notified of the positive blood culture result. The mean time interval for these patients from registration at the initial visit to report of positive blood culture result was 30.0 hours and, from registration at the initial visit to follow-up visit, was 42.7 hours. Thirty-seven percent of those who returned did so because a follow-up visit was scheduled at the initial encounter, and 13% returned because of persistent illness. Ten children (9.6%), five of whom had been notified of the positive blood culture, returned with serious illnesses. Patients whose diagnosis of serious illness was facilitated by blood culture results had shorter delay in identifying cultures as positive than did patients notified of positive results who did not develop serious illness (16.2 vs 31.6 hours; P < 0.05). The delay in follow-up of children with occult bacteremia limits the usefulness of blood cultures in the early detection of serious illness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1408975 TI - The usefulness of pulse oximetry in evaluating acutely ill asthmatics. AB - To examine the usefulness of pulse oximetry in determining the severity of acute asthma, the arterial oxygen saturation (SaO2) of 196 acutely ill asthmatic children was measured while the children were being treated in the emergency department (ED). The measure of severity used was the disposition from the ED- discharge or hospitalization--after receiving standard ED care. The mean pretreatment SaO2 of the 172 children discharged was 96.4% (range, 84-100%), and that of the 24 children admitted was 94.4% (range, 85-100%). A Receiver Operating Characteristic curve indicated that the optimal cutoff point for identifying disposition was an SaO2 of 93%. The sensitivity of an SaO2 < or = 93% was 35%, and the specificity was 92%. We conclude that SaO2 lacks the sensitivity to differentiate the child who will respond to ED therapy from the child who will require further inpatient care. PMID- 1408976 TI - Quality of pediatric care at a freestanding emergency facility. AB - The last decade has seen the introduction of freestanding emergency facilities, which provide an alternative to hospital emergency departments. The contribution made by these facilities to the clinical welfare of patients depends on their availability to deliver quality medical care without the need for frequent referral. This study describes the clinical experience of one such facility with pediatric patients and attempts to assess the quality of their care. PMID- 1408977 TI - Albuterol overdose: a case report and differential diagnosis. AB - The increase in the use of selective beta 2 agonists as first-choice agents in the therapy of asthma has resulted in a concomitant increase in overdoses and other therapeutic misadventures. This case describes a 22-month-old child who ingested a large overdose of albuterol, resulting in an acute syndrome consisting of agitation, tremulousness, marked hyperglycemia of > 320 mg/dl (17.8 mmol/L), ketonuria, and hypokalemia. Such toxicity has generally been reported only in diabetics or pregnant patients. These findings and a brief review of the pharmacology and toxicology of beta 2 agonists are detailed, with special emphasis on the differential diagnosis of overdoses characterized by hyperglycemia, hypokalemia, agitation, and tremulousness. A system of ordering the relative toxicity of these (and other) drugs is proffered using the exposure case fatality rate (ECFR) as a crude measure of clinical toxicity (while delineating its shortcomings). Applying the ECFR (using American Association of Poison Control Centers' data base) to beta 2 agonist overdoses indicates that the resulting clinical syndrome, while troublesome, generally results in a benign outcome. PMID- 1408979 TI - Evaluation of the patient with neck complaints following tonsillectomy or adenoidectomy. AB - The emergency physician should be cognizant of the potential postoperative complications of tonsillectomy or adenoidectomy. Two unusual cases are presented to illustrate the differential diagnosis of the postoperative complaint of neck stiffness. PMID- 1408978 TI - The Romano-Ward syndrome: a case presenting as near drowning with a clinical review. AB - Patients with the Romano-Ward syndrome, a form of congenital long Q-T syndrome (LQTS), present with syncopal episodes and are at risk for sudden death. Patients with LQTS may be misdiagnosed if the physician is unaware of this entity. The risk of sudden death makes recognition important so that appropriate therapy can be initiated. A case is discussed in which the patient presented following a near drowning episode. Family history revealed a familial "seizure disorder." After analysis of the patient's and father's ECGs, the diagnosis of Romano-Ward syndrome was made. A review of the literature was done, concentrating on presentation, pathophysiology, electrocardiographic findings, etiology, diagnosis, prognosis, and treatment of congenital LQTS. This paper is presented to emphasize the importance of physician awareness of LQTS because of the risk of sudden death. Proper diagnosis can lead to treatment that is effective in reducing mortality by more than 90%. PMID- 1408980 TI - Mass illness at an intermediate school: toxic fumes or epidemic hysteria? AB - The report of an acute illness involving a large number of clustered children will undoubtedly provoke an urgent emergency care response or, in some instances, a mass casualty or disaster response. While responding to the perceived needs of those involved, the professionals caring for these children must consider epidemic hysteria along with the other causes of mass illness. Since the early recognition of epidemic or mass anxiety hysteria can have tremendous impact on the ease of treating this problem, that awareness is quite important. PMID- 1408982 TI - Pediatric diabetic ketoacidosis: pathophysiology and potential for outpatient management of selected children. PMID- 1408981 TI - Risk factors for childhood sledding injuries: a case-control study. AB - We report the results of a case-control study designed to identify modifiable risk factors for childhood sledding injuries. Cases included all children injured while sledding (n = 17) during a five-day winter storm who presented for care to a Seattle pediatric emergency department. Two controls were chosen randomly for each case from children who presented to the same emergency department during the ensuing two months for any illness that did not require hospitalization. To qualify as controls, children had to have sledded during the same five-day period but not sustained an injury requiring medical attention. Data were collected on cases and controls using a telephone questionnaire. Analysis of risk factors revealed a significant increase in risk of injury for children who sledded in streets versus those who sledded in a park (OR = 5.1; 95% CI = 1.1-24.1), those who sledded without adult supervision (OR = 5.6; 95% CI = 1.1-26.9), and those whose parents had an annual income > or = $50,000 (OR = 5.7; 95% CI = 1.5-20.8). No difference in risk of injury was found regarding the type of sled used, the number of children, or their position on the sled or for those children with a history of prior sledding experience. We conclude that safe alternatives to sledding in the streets and an increase in adult supervision may reduce the number of childhood sledding injuries. PMID- 1408983 TI - Battery-powered defibrillator/monitors. PMID- 1408984 TI - Motor vehicle accident: abdominal pain. PMID- 1408985 TI - A three year old with Down's syndrome and pneumonia. PMID- 1408986 TI - Erroneous diagnosis within the cranial vault. AB - The majority of pediatric neoplasias of the brain are midline growths in the posterior fossa. These mass lesions lead to obstruction of cerebrospinal fluid circulation and cause increased intracranial pressure. Affected children typically present with insidious complaints of headache and vomiting. Ataxia, cranial nerve palsies, or pyramidal tract signs may be present at the time the diagnosis is entertained. In the reports describing pathognomonic clinical features of posterior fossa tumors, an accelerated presentation with minimal prodromal events has not been emphasized. This report details the case of a child with a cerebellar medulloblastoma who presented with abrupt onset of fever, nuchal rigidity, and altered mental status. Emergency department misdiagnosis occurred. PMID- 1408987 TI - Lumbar puncture for first febrile seizure? PMID- 1408988 TI - Indications for LP in children with fever and a seizure. PMID- 1408989 TI - Indications for LP in children with fever and a seizure. PMID- 1408990 TI - Dealing with police and criminal matters in the ED. PMID- 1408991 TI - [Effect of captopril on glutathione level in the liver and paracetamol-induced liver damage in rats]. AB - Captopril, an inhibitor of angiotensin converting enzyme is widely used in the treatment of hypertension and congestive heart failure. It contains active sulfhydryl group and shares other structural feature with cysteine, the main substrate of glutathione. Experiments were undertaken to examine the effect of captopril on concentration of endogenous glutathione in the liver and to examine the ability of captopril to protect against paracetamol-induced hepatotoxicity. Single doses of captopril (30 mg/kg) given to male Sprague-Dawley rats produced a significant time dependent depletion of hepatic glutathione: at 3 h--16% (controls--10% as the effect of fasting; p less than 0.02), at 5 h--25% (controls -17%; p less than 0.02). Pretreatment of rats with single doses of captopril (30 mg/kg) 2 hours prior to administration of toxic doses of paracetamol (2500 mg/kg) produced a significant depletion of hepatic glutathione level as compared with animals without pretreatment with captopril (median: 2.95 mumol/g liver and 3.50 mumol/g liver, respectively; p less than 0.01). This was not accompanied by a difference in the hepatotoxic effect of paracetamol as assessed by histological staging of necrosis. Studies on covalent binding of paracetamol showed that neither captopril at the doses 30 mg/kg, nor penicillamine (20 mg/kg) affected covalent binding of paracetamol metabolites to cell protein. The results suggest that captopril despite its structural similarity to cysteine depletes hepatic glutathione level and does not protect against paracetamol hepatotoxicity. PMID- 1408992 TI - [Changes in the parameters of respiratory function tests in Raynaud's disease]. AB - Patients with Raynaud's phenomenon can demonstrate arterial spasm not only in hands but also in other organs. The aim of this study was to investigate pulmonary function in 15 patients with Raynaud's disease and in 8 healthy controls before and after cold pressor test. Before the cold pressor test no significant differences in pulmonary parameters between the patients and the controls were observed. After cold pressor test, a statistically significant decrease in diffusing capacity (DLCO) was observed in the study group, but not in the controls. Total lung capacity (TLC) was also slightly decreased. No significant changes of specific diffusing capacity (D/VA) and flow-volume curve parameters (FEF50, FEF25) were noticed. PMID- 1408993 TI - [Hepatitis B virus DNA polymerase activity in various clinical forms of HBV infection]. AB - The aim of the study was to test the clinical value of HBV DNA polymerase (DNAp) determination in patients with various forms of HBV infection, namely: acute hepatitis, chronic hepatitis, cirrhosis and healthy HBV carriers. The determination of DNAp was found to be particularly useful in patients with chronic HBV infection with active virus replication (HBeAg+) independent of histopathological changes. PMID- 1408994 TI - [Effect of coronary artery patency after myocardial infarction on ventricular late potentials]. AB - This study evaluated the relation between patency of the infarct related artery and the presence of ventricular late potentials (VLP) on the signal-averaged electrocardiogram (ECG). 44 patients (pts) after myocardial infarction (MI) (35 men, 9 women; mean age 50 years) were studied by coronary angiography. measurement of ejection fraction and signal-averaged ECG. The infarct-related artery was closed in 15 pts and open in 29 pts. There was no difference in age, previous MI and location of infarct between the two study groups. Thrombolytic therapy in acute stage of MI was significantly often (p less than 0.05) in pts with open (59%) than closed (13%). The incidence of VLP was significantly higher (p less than 0.05) in group of pts with closed (40%) than open artery (7%). These data indicate that patency of the infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias. PMID- 1408995 TI - [Allergy to house dust mites--its clinical significance and current methods of prevention]. PMID- 1408996 TI - [Effectiveness of empirical antibiotic therapy in the control of infections in patients with acute leukemia during severe neutropenia]. AB - The clinical efficacy of empiric antibiotic treatment regimen for infection in 38 neutropenic patients with acute leukemia during induction and intensification therapy was evaluated. The therapy, which was applied in 74 episodes of fever in patients with neutrophil count less then 0.5 G/l, consisted of three sets of antibiotics (gentamycin + carbenicillin or azlocillin, amikacin + cephradine++ or cefuroxime, netilmicin+cefotaxime or ceftazidime) used one after another in case of persistence of fever in spite of 72 hours of treatment: In addition, flucytosine was applied in case of stable fever after 72 hours of antibiotic therapy. Flucytosine was replaced by amphotericin after 72 hours of ineffective treatment. The response rate of 68% and 96% was observed for patients during induction and intensification chemotherapy respectively. Low clinical efficiency of gentamicin and carbenicillin/azlocillin during induction treatment indicates that the therapy with antibiotics of broader range of activity is needed for this group of patients. PMID- 1408997 TI - [Our experience with the diagnosis of peritonitis complicating a long-term program of peritoneal dialysis]. AB - Among 37 patients (pts) with irreversible renal failure treated in years 1980 1990 with chronic peritoneal dialysis there were 18 treated with continuous ambulatory peritoneal dialysis (CAPD) and 19 treated with standard intermittent peritoneal dialysis (SIPD). Mean frequency of peritonitis (P) was 1 episode per 9.0 patients-months. The important symptoms for early diagnosis of P were as follows: cloudiness of peritoneal effluent (PE) and high (more than 50%) percentage of polynuclear cells in the smear of PE sediment. Positive results of PE culture were obtained only in 50% of P episodes in years 1980-1985, mostly in pts treated with CAPD (17/21 pts). In the period of 1986-1990, in pts treated mostly with SIPD (15/16 pts), positive results were obtained in 80% of P. Improvements of bacteriological diagnosis of P, especially in pts treated with CAPD, were discussed. "Prophylactic" cultures of PE were found to be of no value. PMID- 1408998 TI - [2 cases of Sneddon syndrome]. AB - Two cases of Sneddon syndrome (S.s.) in a 33 and 53-year-old women who developed arterial hypertension, cerebral ischaemic signs and who have livedo reticularis or livedo racemosa, are reported. The authors describe clinical, radiological and biological features of this rare disease, as well as diagnostic investigations including the measurements of the antiphospholipid antibodies (APA). The possible role of APA in the pathogenesis of S.s. is discussed. PMID- 1408999 TI - Two FMRFamide-like peptides from the free-living nematode Panagrellus redivivus. AB - Peptides of the FXRFamide family, where X = M, I or L, are broadly distributed among invertebrates. Two such peptides were purified and sequenced from the free living nematode, Panagrellus redivivus. Immunohistochemical techniques localized FMRFamide-like material in several regions of these organisms, including the nerve cords and, most prominently, in paired groups of cells located caudally to the base of the pharynx. RIA determinations gave an estimate of 2.8 nmol immunoreactive peptide/g of an acetone extract of P. redivivus. Four sequential HPLC purification steps, followed by sequencing by automated Edman degradation and FAB-MS, led to the identification of Ser-Asp-Pro-Asn-Phe-Leu-Arg-Phe-amide (SDPNFLRFamide) and Ser-Ala-Asp-Pro-Asn-Phe-Leu-Arg-Phe-amide (SADPNFLRFamide) as members of the FXRFamide family in this nematode. PMID- 1409000 TI - Purification and chemical characterization of caudodorsal cell hormone-II from the egg-laying controlling caudodorsal cells of Lymnaea stagnalis. AB - Caudodorsal cell hormone-I (CDCH-I), a 36 amino acid peptide synthesized by the caudodorsal cells (CDCs), is one of the major neuropeptides present in the cerebral ganglia of the freshwater snail, Lymnaea stagnalis. This peptide induces ovulation and egg-mass formation, and, in addition, acts on neuronal circuits involved in the control of overt egg-laying behavior. cDNA cloning studies revealed that there is a CDCH gene family comprising two genes coding for CDCH-I and the related yet distinct CDCH-II, respectively. In the present study, using sequential high performance gel permeation and reversed phase high performance liquid chromatography, we have isolated and sequenced the peptide CDCH-II. This neuropeptide has the following sequence: Ser-Ile-Thr-Asn-Asp-Leu-Arg-Ala-Ile-Ala Asp-Ser-Tyr-Leu-Tyr-Asp-Gln-His- Lys-Leu - Arg-Glu-Gln-Gln-Glu-Glu-Asn-Leu-Arg Arg-Arg-Phe-Tyr-Glu-Leu-Ser-Leu-Arg- Pro-Tyr - Pro-Asp-Asn-Leu. The sequence differs from those predicted by the cDNA sequence encoding preproCDCH-II at two positions, suggesting the polymorphism of CDCH-II exists in L. stagnalis. PMID- 1409001 TI - Potent inhibition of gastric acid secretion by intravenous interleukin-1 beta and -1 alpha in rats. AB - The influence of human and rat recombinant interleukin-1 (hIL-1 beta and -1 alpha and rIL-1 beta) on acid secretion was investigated in conscious pylorus-ligated rats. Intravenous injection of either hIL-1 beta, hIL-1 alpha or rIL-1 beta dose dependently inhibited gastric acid output with an ED50 of 0.05 microgram, 0.5 microgram and 2.2 micrograms, respectively. The antisecretory action of IL-1 beta was associated with an increase in circulating levels of gastrin. hIL-1 beta induced inhibition of acid secretion was dose dependently reversed by peripheral injection of the IL-1 receptor antagonist, IL-RA, with a dose ratio of 1:10(3) for complete reversal. The inhibitory effect of hIL-1 beta was blocked by indomethacin and was not modified by IV injections of the CRF receptor antagonist, alpha-helical CRF(9-41), or the monoclonal somatostatin antibody CURE.S6, or by systemic capsaicin pretreatment. These results show that systemic hIL-1 beta-induced inhibition of gastric acid secretion is mediated through IL-1 receptors and prostaglandin pathways, and does not involves CRF receptors, afferent fibers, or changes in circulating gastrin or somatostatin levels. PMID- 1409002 TI - Control of pepsin secretion by regulatory peptides in the rat stomach: comparison with acid secretion. AB - Previous studies of the control of pepsin secretion by neurohumoral agents showed some discrepancies between in vitro (isolated cells) and in vivo experiments. In the present work, the effects on pepsin secretion of CCK, pentagastrin, secretin, VIP, neurotensin, histamine, and methacholine were reinvestigated in conscious gastric fistula rats, in comparison to acid secretion. ED50's and doses inducing maximal responses were measured to directly compare the potency and efficacy of these substances. Methacholine was the most efficient (maximal response = 4.5 x basal level, ED50 = 1.3 mumol/kg.h) and CCK the most potent (ED50 = 1.9 nmol/kg.h) stimulant, whereas secretin was a potent (ED50 regulators of pepsin secretion in the rat. Pentagastrin and histamine did not stimulate pepsin output, as found by others with isolated chief cells in vitro. Neurotensin and large doses of VIP marginally inhibited pepsin secretion. PMID- 1409003 TI - LHRH in the ferret: pubertal decrease in the number of immunopositive arcuate neurons. AB - This study correlated a region-specific change in the number of luteinizing hormone-releasing hormone-immunopositive (LHRH+) neurons with pubertal development in male ferrets. There were 50% fewer LHRH+ cell bodies in the arcuate nucleus of peri- and postpubertal ferrets than in prepubertal ferrets; this significant decrease represented a 15% reduction in the overall number of LHRH+ neurons. Intracerebroventricular colchicine did not reveal additional numbers of LHRH+ neurons in the arcuate nucleus, indicating that the pubertal decrease in arcuate LHRH+ cell bodies was not due to rapid transport of peptide. These results suggest that LHRH of arcuate origin may inhibit release of LHRH via ultrashortloop negative feedback in prepubertal ferrets. Cessation of peptide production in half of the arcuate LHRH neurons at puberty could result in a reduction in this inhibitory signal that permits the pubertal increase in LHRH/LH release. Alternatively, LHRH of arcuate origin may have a nonpituitary role. In either case, these data provide evidence for heterogeneity of function among LHRH+ neurons. PMID- 1409004 TI - Selective ablation of spinal afferent neurons containing CGRP attenuates gastric hyperemic response to acid. AB - The gastric mucosa, in particular submucosal blood vessels, are innervated by afferent neurons containing neuropeptides such as calcitonin gene-related peptide. Stimulation of sensory neurons innervating the gastric mucosa increases submucosal blood flow. Since sensory neurons supplying the stomach are of dual origin from nodose and dorsal root ganglia, we examined the effect of selective ablation of either the vagal or spinal sensory innervation to the upper gastrointestinal tract on the increase in gastric mucosal blood flow in response to acid back diffusion into the gastric mucosa. Perineural application of capsaicin to the celiac/superior mesenteric ganglia, but not to the vagus nerves, significantly inhibited by 53% the hyperemic response to acid back diffusion. Tissue levels of immunoreactive calcitonin gene-related peptide in the gastric corpus were significantly reduced (by 73%) by periceliac capsaicin treatment, but unaffected by perivagal capsaicin treatment. These data suggest that spinal capsaicin-sensitive afferents containing calcitonin gene-related peptide immunoreactivity are involved in mediating increases in gastric mucosal blood flow. This increase in gastric mucosal blood flow mediated by sensory neurons may act as a protective mechanism against mucosal injury, similar to responses seen in other tissues such as skin. PMID- 1409005 TI - Naloxone blocks opioid peptide release in periaqueductal gray and amygdala elicited by morphine injected into N. accumbens. AB - Previous studies from this laboratory suggested that the periaqueductal gray (PAG), nucleus accumbens, and amygdala might take part in a serial, unidirectional mesolimbic loop to play their roles in pain modulation. It has been proposed that morphine injected into one of these nuclei would cause the release of opioid peptides in one nucleus after another. This working hypothesis was examined in the present study by perfusing simultaneously the PAG and the amygdala after microinjection of morphine into the N. accumbens. It was found that microinjection of morphine increased the content of immunoreactive enkephalins (ir-ENK) and immunoreactive beta-endorphin (ir-beta-EP) in the perfusate of the PAG and the amygdala. When the perfusion fluid contained 3 microM of naloxone, the increase of ir-ENK and ir-beta-EP was reduced significantly. These results indicate that the three nuclei were not serially connected in a unidirectional loop. PMID- 1409007 TI - Evidence against autocrine feedback regulation of cholecystokinin secretion in man. AB - To determine whether exogenous cholecystokinin (CCK) inhibits endogenous CCK release, cholecystokinin-8S (CCK-8S) was infused intravenously during continuous intraduodenal stimulation of endogenous CCK by a meal. CCK was measured in plasma by 2 region-specific radioimmunoassays employing antibodies T204 and 1703. AB T204 binds to carboxy-terminal CCK peptides containing the sulphated tyrosyl region, including CCK-8S, and AB 1703 to carboxy-terminal CCK peptides containing at least 14 amino acid residues. Meal-stimulated plasma CCK concentrations remained elevated during the entire infusion period. CCK-8S infusion further increased meal-stimulated plasma CCK concentrations, when measured with AB T204, while meal-stimulated plasma CCK concentrations were not suppressed by CCK-8S infusion, when measured with AB 1703. It is concluded that meal-stimulated endogenous CCK release is not affected by the effects of intravenously administered CCK-8S. These data suggest that autocrine feedback regulation of CCK release is not operative in man. PMID- 1409006 TI - Pseudononapeptide bombesin antagonists containing C-terminal Trp or Tpi. AB - Seven new antagonists of bombesin (Bn)/gastrin-releasing peptide (GRP) containing C-terminal Trp or Tpi (2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-3-carboxylic acid) in a reduced peptide bond were synthesized by solid phase methods and evaluated biologically. The reduced bond in four [Leu13 psi(CH2NH)Trp14]Bn(6-14) analogs was formed by reductive alkylation at the dipeptide stage. In the case of three [Leu13 psi(CH2N)Tpi14]Bn(6-14) analogs, the Trp dipeptide with reduced bond was reacted with formaldehyde to form the corresponding Tpi derivative. These Tpi containing analogs have a new reduced bond which is structurally more constrained. Leu13 psi(CH2N)Tpi14 analogs inhibit [125I][Tyr4]bombesin binding to Swiss 3T3 cells with IC50 values of 2-4 nM, compared to 5-10 nM for Leu13 psi(CH2NH)Trp14 analogs. Leu13 psi(CH2N)Tpi14 analogs are also more potent than Leu13 psi(CH2NH)Trp14 analogs in growth inhibition studies using Swiss 3T3 cells. The two best bombesin antagonists of this series, [D-Trp6,Leu13 psi(CH2N)Tpi14]Bn(6-14) (RC-3415) and [Tpi6,Leu13 psi(CH2N)Tpi14]Bn(6-14) (RC 3440), inhibited GRP-stimulated growth of Swiss 3T3 cells with IC50 values less than 1 nM. RC-3440 was also active in vivo, suppressing GRP(14-27)-stimulated serum gastrin secretion in rats. Bombesin/GRP antagonists, such as RC-3440, containing the new reduced bond (CH2N) reported herein are very potent. PMID- 1409008 TI - Atrial natriuretic factor (ANF) binding sites in frog kidney and adrenal. AB - Atrial natriuretic factor (ANF) binding sites were localized and quantified in kidney and adrenal of the frog Rana temporaria by quantitative in vitro autoradiography. [125I]-rat ANF(99-126) binding was present in kidney glomeruli and in the outer layer of interrenal tissue in the adrenal gland. ANF binding exhibited positive cooperativity with a half-maximal binding concentration (EC50) of 102 +/- 16 pM in glomeruli and 93 +/- 19 pM in interrenal tissue (n = 8). The corresponding maximal binding capacities (Bmax) were 1.33 +/- 0.16 and 1.21 +/- 0.36 fmol/mm2. [125I]-Rat ANF(99-126) binding was competitively displaced by unlabeled ANF analogues with an intact disulfide bridge showing a lower affinity than the iodinated ligand. The presence of ANF binding in glomeruli and steroidogenic interrenal cells suggests physiological functions of ANF for the osmomineral regulation in the frog by influencing glomerular filtration rate and adrenal steroid secretion. PMID- 1409009 TI - Comparison of TRH and its analog (NS-3) in thermoregulatory and cardiovascular effects. AB - The effects of TRH and its metabolically stable analog NS-3 [(3R,6R)-6-methyl-5 oxo-3-thiomorpholinylcarbonyl-L-histidyl-L-pro linamide tetrahydrate] on thermoregulation and circulatory control have been investigated. Both NS-3 (1-100 ng/kg ICV) and TRH (0.1-10 micrograms/kg ICV) increased rectal temperature and metabolic rate with a transient cutaneous vasoconstriction in conscious rabbits. They also increased arterial blood pressure, heart rate, respiratory rate, and renal sympathetic nerve activity (RSNA) in urethane-anesthetized rabbits. Ten ng/kg of NS-3 and 10 micrograms/kg of TRH had comparable hyperthermic, pressor, and tachycardic activities, while the relative potency of NS-3 to increase RSNA was greater and that to increase metabolic rate was smaller than the other effects. In conclusion, NS-3 was more potent than TRH in all of the effects measured, but there was a dissociation in the relative potency of NS-3 in the different autonomic effects. PMID- 1409010 TI - Pharmacological characterization of angiotensin II binding sites in the canine pancreas. AB - High affinity 125I-angiotensin II (Ang II) binding sites were characterized in the canine pancreas. Total binding increased with protein concentration and equilibrium was reached within 60-90 min at 22 degrees C. Specific binding was saturable and averaged 70% of total. Scatchard analysis of binding yielded a KD of 0.48 +/- 0.18 nM with a Bmax of 32.8 +/- 6.5 fmol/mg protein (mean +/- SEM, n = 6). The addition of the reducing agent dithiothreitol increased specific binding two-fold. The rank order of displacement of 125I-Ang II binding by native angiotensin peptides was Ang II greater than or equal to Ang III greater than AngI greater than Ang(1-7) much greater than Ang(1-6). The use of the specific Ang II antagonists CGP 42112A, PD 123177, and DuP 753 revealed that the pancreas expresses two receptor subtypes. The majority of Ang II binding sites in the pancreas could be classified as type 2 (AT2), although type 1 (AT1) sites were also detected. In vitro autoradiography revealed binding sites localized over islet cells, acinar and duct cells, as well as the pancreatic vasculature. In addition, the autoradiographic studies confirmed the predominance of the AT2 receptor subtype throughout the pancreas. PMID- 1409011 TI - Pepsin-mediated processing of synthetic precursor-like sequence yields neurotensin-like peptide. AB - A 15 amino acid synthetic peptide, which spanned the dibasic cleavage site C terminal to neurotensin (NT), in its 170-residue canine precursor, was synthesized by solid-phase methods. Using this substrate in combination with a radioimmunoassay specific for the C-terminal region of NT, a simple assay was developed to monitor protease-mediated cleavage of the Leu8-Lys9 bond in the substrate. Hog pepsin and the related enzymes, rhizopus pepsin, bovine cathepsin D, and mouse renin, were found to be effective in this assay, pepsin cleaving only this bond to liberate the NT-like sequence. The pH dependence of the reaction indicated that pepsin, cathepsin D, and renin exhibited significant activity at pH's characteristic for secretory vesicles (pH 5.5-6.5). In addition, pepsin and cathepsin D were shown to process the native precursor at pH's as high as 5.5. These results, although not proof, are consistent with the idea that endoproteases with pepsin-like specificity may be involved in the processing of the NT precursor in neural/endocrine cells. PMID- 1409012 TI - Capsaicin does not attenuate bombesin-induced suppression of operant responding for food reward. AB - Systemic treatment with capsaicin, a neurotoxin which damages unmyelinated peptide-containing sensory neurons, has been shown to attenuate bombesin (BBS) induced suppression of food intake. To determine whether capsaicin-sensitive fibers mediate the effect of BBS on appetitive motivation, we examined BBS induced suppression of operant responding in rats pretreated neonatally with capsaicin (50 mg/kg; SC) or control vehicle. At 8-10 weeks of age, rats were trained to bar press for food. After achieving a stable level of performance, the animals were injected with BBS (10 micrograms/kg), normal saline, or prefed with 20 Noyes 45-mg pellets. Animals were then tested in an operant chamber on an FR 5 schedule of reinforcement for one hour. The results indicated that BBS suppressed bar pressing, regardless of whether animals were pretreated with capsaicin or control vehicle. These findings are inconsistent with the hypothesis that BBS induces satiety via capsaicin-sensitive neurons. The results suggest the possibility that more than one mechanism may mediate the effects of BBS: a neural mechanism involved in consummatory responses and a humoral mechanism involved in the operant response. PMID- 1409013 TI - Angiotensin II binding sites in frog kidney and adrenal. AB - Angiotensin II (AII) binding sites were localized and quantified in kidney and adrenal of the frog Rana temporaria by quantitative in vitro autoradiography. AII binding was present in kidney glomeruli and in interrenal tissue of the outer zone of the adrenal gland. Saturation experiments showed that [125I]-[Val5]AII binds to a single class of binding sites with a dissociation constant (Kd) of 548 +/- 125 pM in glomeruli and 593 +/- 185 pM in interrenal tissue (n = 8). The corresponding maximal binding capacities (Bmax) were 2.48 +/- 0.71 and 3.05 +/- 1.02 fmol/mm2, respectively. AII binding was displaced by unlabeled angiotensin analogues in the rank order: [Sar1]AII greater than human AII greater than [125I] [Val5]AII = [Val5]AII = human AIII much greater than human AI. The AII binding sites in glomeruli and interrenal tissue suggest an influence of AII on glomerular filtration rate and adrenal steroid secretion to take part in osmomineral regulation of the frog. PMID- 1409014 TI - Heart and plasma atrial natriuretic peptide (ANP) in response to long-term endurance training in rats. AB - Long-term endurance training effects on heart and plasma ANP were investigated in male Wistar rats. Maximal O2 uptake (VO2max) was significantly higher in trained groups, when they are used as their own control. After 3, 4, and 5 weeks of endurance training, VO2max was respectively increased by 7.7% (p less than 0.05), 13.7% (p less than 0.01), and 18.4% (p less than 0.001). Plasma ANP and glomerular ANP receptor density showed no clear variations in trained rats. However, cardiac ANP content decreased significantly in left and right atrial tissues by 35-36% (p less than 0.05) after 5 weeks of training. ANP immunoreactivity was investigated to show the distribution of ANP within the atria. ANP was found in diffuse and granular forms. The diffuse pattern (immature ANP) disappeared in cardiocytes of trained rats, while the granular form persisted, especially in the left atrial tissue. These data suggest that chronic endurance training might cause a decrease in ANP synthesis with no change in ANP storage. Such results are in agreement with the hypothesis that the left atrium could be especially involved in long-term fluid volume control. PMID- 1409015 TI - Vasopressin, corticosterone levels, and gastric ulcers during food-restriction stress. AB - Corticosterone levels and ulcers were compared in vasopressin-containing (LE) and vasopressin-deficient (DI) rats under ad lib and food-restricted conditions. In the ad lib situation, DI and LE rats had similar corticosterone levels and no ulcers. After 1 day of food restriction, the corticosterone levels were elevated in DI and LE rats, with a significantly higher level in LE rats. No ulcers were present in either strain. After 2 days of food restriction, the corticosterone levels were similar in DI and LE rats. The level in DI rats was comparable to that of the preceding day, but the level in LE animals dropped significantly from the previous day. Significant ulceration was evident in DI rats, but absent in LE rats. Following 3 days of food restriction, the corticosterone level in LE rats had returned to the ad lib level, whereas, for DI rats, an elevated level was maintained. There were no ulcers in LE rats, but they were present in DI rats. Thus LE and DI rats responded differently to the stress of food restriction. The mechanism underlying the response is most likely related to changes in the hypothalamic-pituitary-adrenocortical axis and its reaction to stress. PMID- 1409017 TI - Single-step isolation and sequencing of vasopressin and oxytocin precursors. AB - The pre- and post-Golgi processing of preprovasopressin and prepro-oxytocin was evaluated by microsequencing for incorporated radiolabel. 35S-Cysteine and 3H fucose were microinjected into rat supraoptic nuclei (SON), and proteins and peptides related to the biosynthesis of vasopressin (VP) and oxytocin (OT) were isolated at various times from the supraoptic nuclei and neural lobe by employing a one-step procedure of high performance liquid chromatography (HPLC). These proteins and peptides were recognized through their binding to specific antibodies against VP, OT, and rat neurophysins (RNPs), and by their binding to ConA-Sepharose. Two immunoreactive glycoproteins related to VP biosynthesis were recovered from the SON and both contained fucose and had a 35S-cysteine placement consistent with the location of the hormone sequence at the N-terminus. SDS electrophoresis revealed the major protein form to be 21,000 daltons and the minor protein form to be 19,000 daltons. One nonglycosylated protein of 16,000 daltons related to oxytocin biosynthesis was recovered from the SON, and this protein also had a 35S-cysteine placement consistent with an N-terminal OT sequence. These data provide the first sequential evidence that prior to, or shortly after, packaging in the Golgi the preprohormones of VP and OT have lost their entire leader-peptide structures. PMID- 1409016 TI - Effect of vasopressin administration and deficiency upon 3H-AVP binding sites in the CNS and periphery during development. AB - Arginine8-vasopressin (AVP, 40 micrograms/100 g b.wt., SC) was administered to male Long-Evans (LE) pups from day 1 to 7 of life and the pups were sacrificed on day 8 or 60. 3H-AVP binding was performed on membranes prepared from the liver, kidney, and septum. No significant changes were observed in the kidney or septum of animals 8 or 60 days old. However, the chronic AVP treatment did result in a significant increase in the density of 3H-AVP binding sites in the liver when compared to control day 8 pups (control 44 +/- 2 vs. AVP 56 +/- 3 fmol/mg protein), with no change in affinity. This effect was maintained into adulthood, as the day 60 AVP-treated LE rats also showed a significant increase in liver 3H AVP binding sites compared to control (control 186 +/- 9 vs. AVP 239 +/- 14 fmol/mg protein), with no change in affinity. A comparison of 3H-AVP binding sites in 8-day-old LE, heterozygous Brattleboro (HET-BB), and homozygous Brattleboro rats (HOM-BB) was performed to assess the effect of complete (HOM-BB) and partial (HET-BB) VP deficiency on binding sites in the CNS and periphery. The liver again was the only tissue in which a change in 3H-AVP binding characteristics was noted. The HOM-BB rat (Bmax 144 +/- 6 fmol/mg protein) displayed a significant increase in AVP binding sites from the LE rat (Bmax 100 +/- 7 fmol/mg protein), while the 3H-AVP binding sites in the HET-BB rat liver (Bmax 69.8 +/- 9 fmol/mg protein) were significantly lower than LE rats. Thus hepatic AVP receptors appear most sensitive to the presence or absence of vasopressin during the early postnatal period. PMID- 1409018 TI - The use and reliability of psychiatric diagnosis in forensic settings. AB - The clinical professional encounters conflict whenever he or she enters the courtroom. The psychiatrist's approach must not be simply diagnostic or simply legal. We cannot shed our clinical identity; indeed, the court depends on our clinical identity and expertise in its search for the truth. The psychiatric expert must be able to translate his or her findings for the court, but these findings must come from clinical experience, not some solely legal perspective. The legal system needs our knowledge about the interfaces of mental illness, function, and behavior. After we provide our opinions, however, the legal issues must be left to the lawyers and the final determinations left to the judge or jury. PMID- 1409019 TI - Clinical forensic psychiatry. PMID- 1409020 TI - Mentally disordered offenders. Patterns in the relationship between mental disorder and crime. AB - Five patterns among mentally disordered offenders are distinguished by the relationship between mental disorder, on the one hand, and criminality, on the other. Pattern 1 offenders are those for whom crime is a response to psychotic symptoms, most often delusions or hallucinations. Pattern 2 offenders commit crimes motivated by compulsive desires, such as sex offenses by paraphiles and offenses regarded as evidence of disorders of impulse control. Pattern 3 offenders are those with personality disorder for whom the crime is merely one example of a maladaptive pattern of voluntary and knowing behavior. Pattern 4 offenders have coincidental mental illness that is unrelated to the crime. Pattern 5 offenders are those who become mentally disordered or feign mental disorder as a result of their crimes, such as those who dissociate upon seeing what they have done, those who become depressed in prison, those who become psychotic on death row, and those who malinger mental illness. Although these categories do not determine whether offenders are responsible for their behavior, some unknown proportion of Pattern 1 offenders do meet legal criteria for insanity, depending on the facts of each case and the applicable legal standards. It is arguable whether or not Pattern 2 offenders ever meet legal criteria of insanity. Offenders evidencing only Patterns 3, 4, or 5 are not candidates for an insanity defense. PMID- 1409021 TI - Major affective disorders and forensic psychiatry. AB - Major mental illnesses, such as major affective disorders and schizophrenias, form a relatively small diagnostic group among mentally disordered offenders. The major affective disorders are less common when compared with schizophrenics among such offenders. Yet, some of the most violent crimes, such as murder, attempted murder, and serious assaults, especially intrafamilial violence, are committed by major affective disorder patients. The offenses by this group of patients are committed while suffering from active symptoms of the illness. As such, a substantial majority is not considered fully criminally responsible for the offense. Many such offenders are found not guilty by reason of insanity and are sent to psychiatric hospitals. PMID- 1409022 TI - The forensic psychiatric aspects of schizophrenia. AB - This review of the literature does seem to reveal an association between schizophrenia and a variety of antisocial behaviors that include violent crime, and even homicide, especially in North America. The literature consistently shows that since the 1950s, schizophrenics have been involved in crime and arrested more frequently than the general population, they are overrepresented in correctional settings, and they represent the majority of those found not guilty by reason of insanity. Many authors cite changes in mental health policies, particularly de-institutionalization, as one of the major causes of these phenomena. It is important to note that a history of prior arrests and of being male, poor, unskilled, uneducated, and unmarried are perhaps the best predictors of antisocial behaviors in the mentally ill and in the general population alike. Schizophrenic drift and increased family pathology in schizophrenic families, however, may predispose people suffering from schizophrenia to these demographic variables. Interestingly, these variables do not seem as relevant in the emergency room or inpatient wards where violence seems to be mainly affected by the severity of psychopathology, substance abuse, neurologic signs, and the environment within the mental health setting. The implications for the practice of psychiatry are diverse. Clearly clinicians in both hospitals and community mental health settings must have experience, training, and an awareness of the literature relating to the prevention, causes, and management of violence. It behooves us in the mental health field, having vociferously supported the community mental health movement, to assist police in the management of the mentally ill who are now in the community, perhaps by the use of mobile crisis intervention teams and by a considerably increased amount of effort and cooperation. Correctional services require urging to develop resources for identifying and tracking the mentally ill so as to be able to provide programs and continuity of care. Community mental health and criminal justice systems need to cooperate in planning the transition of mentally abnormal offenders from prisons into the community and then providing support and after-care for them. One exemplary program that has developed and benefited from the coordination and planning at the interministerial level is the Inter-ministerial Project (IMP) program in Vancouver. This program identified the people whose histories revealed repeated admissions to both correctional and mental health facilities, bouncing between one and the other. Using a case management approach with a limited caseload, clinicians were able to reduce the number of admissions to both types of facilities. This program should serve as a model for other jurisdictions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1409023 TI - The involvement of schizophrenic insanity acquittees in the mental health and criminal justice systems. AB - This article described the mental health and criminal justice involvement of a large group of schizophrenic insanity acquittees and the program designed to manage and treat these individuals. Most insanity acquittees in our system are chronically mentally ill individuals who fit well into the psychosocial rehabilitation models that have developed over the past 15 years. In addition, the use of conditional release and monitored care in the community appears to be the most realistic approach to this group of individuals who show a high degree of involvement with the mental health and criminal justice service systems. This research has continued implications for the development of outpatient civil commitment and for the attempt to give people as much liberty as they are capable of handling while being realistic about their capacities to survive in the community. PMID- 1409024 TI - Substance abuse and criminal behavior. AB - As forensic psychiatry develops as a clinical subspecialty, clinical skill in understanding, treating, and predicting violent behavior will become more important. This article addresses the importance of understanding the relationship between substance abuse and violent behavior. This article also discusses morbidity and mortality in substance abuse, the demographics of substance abuse and criminality, and the clinical aspects of the forensic psychiatric evaluation. PMID- 1409025 TI - Arson in review. From profit to pathology. AB - Arson is a crime committed by thousands of people throughout our nation for nearly every reason, justification or excuse known to mankind ... Arson is one of the easiest crimes to commit but the hardest to prevent or prove ... Arson is a crime which involves little skill, as the weapon used is legally carried and too readily available ... Unlike many other covert criminal activities, the impact of increased major arsons has a direct visible effect on the lives of the average citizen. Insurance premiums are raised, property is destroyed, people are killed or maimed, and the quality of life in the area affected by arson is diminished considerably. These statements, taken from US Senate hearings on arson in the late 1970s, are as true and as troubling today as they were over a decade ago. Many who set fires need mental health services of some kind, a fact alluded to even in popular literature. Dick Francis, a well-known author of British mysteries, writes, "There are people in this world who cause trouble because it makes them feel important. They're ineffectual, eh? in their lives. So they burn things ..." But nobody wants these arsonists in their midst. Psychiatric facilities do not want them so they end up in prison: Yet another case has been reported of a mentally disordered person being sent to prison because there is no other institution willing to receive her ... a severely mentally disordered woman aged 22 [was sentenced] to life imprisonment for arson ... in default of other appropriate facilities ... to protect the public. And general hospital emergency rooms cannot find anyplace to send them: "The hardest patients to sell are the repeaters with bad reputations, the firesetters and those who are potentially violent." Any arson episode is an act the magnitude of which the perpetrator cannot predict accurately. Once set, the fire is no longer responsive to the desires or dictates of the firesetter. To address the problem of arson in our times, arson investigators for law enforcement agencies and for insurance companies, fire chiefs, and mental health professionals must develop a joint commitment to public education, cooperative plans for prevention and intervention, and a shared research agenda.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1409026 TI - The pathological gambler as criminal offender. Comments on evaluation and treatment. AB - Over the past three decades, gambling has been the nation's fastest growing industry. Although there is now some leveling off, states are still turning to legalized gambling to address financial problems without having to raise taxes. In addition, there is new technology that produces more rapidly addicting games. States are accepting some responsibility and, as of this writing, 12 of them have funded some programs in public education, research, training, and treatment. Although there are only a half dozen inpatient programs and very few qualified counselors and therapists, we can anticipate the development of clinics, residential programs, halfway houses, and alternative sentencing programs. The National Council on Problem Gambling has developed guidelines for the certification of gambling counselors. In addition to the training of mental health professionals, workshops are needed for attorneys, judges, probation and parole officers, and prison administrators. Initially, the task of assessing and diagnosing the pathological gambler was left to a small number of experts. Starting with DSM-IV, there will be clear and reliable criteria available to the professional community. These criteria, which are the product of thorough testing, should easily discriminate the pathological gambler from other types of gamblers. Most of what we have learned about pathological gambling has come in the last 5 years. A major impetus for research has been the Journal of Gambling Studies, which began publication in 1985. A review of the nature and course of the disorder, including the studies of criminal behavior, leads one to conclude that the majority of pathological gamblers (at least 70% to 80%) commit offenses late in the disorder and that these offenses are strictly gambling related. This is a population which is essentially nonviolent and which turns to property crimes out of desperation over gambling losses and their sequelae. The minority (in one study 14%) of gamblers with antisocial personality disorder--the group for whom treatment would be least likely to be effective--can be recognized easily both by the pattern of offenses and by diagnostic criteria for antisocial personality. Once this group is excluded, treatment for the others, in combination with restitution, community service, and some form of monitoring, would seem beneficial both for the individual and for society. Once they have stopped gambling, pathological gamblers are frequently hard-working people, whose mathematical skills and intelligence, high energy, and need to excel make them extremely valuable at their jobs. The alternative, imprisonment, may very well reinforce the disorder.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1409027 TI - Homicide, infanticide, and filicide. AB - Homicidal behavior appears to be a heterogeneous phenomenon. Although the causative role of mental illness in relation to homicide remains a controversial and debatable issue, recent studies indicate that a significant number of homicidal adults suffer from serious mental illness, more specifically psychosis. Most reports that attempt to correlate the presence of identifiable risk factors and homicide yield inconclusive or unreplicated results. In addition to supporting the need for further research in the area of aggressive behavior and violence, prevention also should involve the use of a multidisciplinary approach in considering the multiple causes and solutions to this problem. PMID- 1409028 TI - The paraphilias. The extent and nature of sexually deviant and criminal behavior. AB - This article presents data that indicate that paraphiliacs tend to carry out a variety of paraphilic behaviors and cross a number of boundaries within individual paraphilias. These data contradict earlier theories that postulated that paraphiliacs compulsively repeat the same category of paraphilia over time without crossing into other categories of paraphilic acts as a result of specific early life experiences or specific emotional conflicts. This article suggests that a more parsimonious explanation is that individuals with paraphilias have a general deficit of control, leading them to carry out a variety of paraphilic behaviors with a variety of victims. PMID- 1409029 TI - Incest perpetrators. Their assessment and treatment. AB - The multitude of articles published in the last decade in the area of intrafamilial sexual abuse highlight the complexity of the issue--both its assessment and treatment. Although no unique profile of an incest perpetrator exists, a review of studies revealed problems in the areas of sexual satisfaction, psychological functioning, interpersonal relationships, and family of origin. As well, incest families have been reported to be dysfunctional, with power imbalances; control struggles; indirect, unclear communication; and inappropriate coalitions among family members. Based on these observations, a wide range of treatment interventions now exists, including offender-oriented cognitive/behavioral therapies and a family-focused multimodal systems approach. Although questions remain to be answered in regard to the effectiveness and process of treatment, efforts limited to the recognition of these problematic families are no longer adequate. The focus must move to prevention through the early identification of individuals at risk both for offending and being part of an incest family structure; the implementation of proven, cost-effective, proactive intervention strategies; and the continuing dissemination of information to the public. PMID- 1409030 TI - The evaluation and treatment of sexual violence, necrophilia, and asphyxiophilia. AB - At first sight the phenomena discussed in this paper may seem to have little in common. Yet on close scrutiny it becomes apparent that there is an interesting degree of overlap. Although sexual assaults in general clearly involve multiple causes or factors, social and cultural as well as individual, many sexual aggressors do show psychological or biologic abnormalities which require careful evaluation. Continued empiric study of the variables discussed in this paper is therefore important. The clinical as well as laboratory study of paraphilias with dangerous tendencies to themselves or others is also essential for a better understanding of the causes and relationships between these disorders. PMID- 1409031 TI - Clinical aspects of forensic assessment of juvenile offenders. AB - Juvenile delinquency is a major public health problem with far reaching consequences not only on the child and the family but also on society generally. Although most individuals who commit crimes as adolescents will stop by age 18, a core group of young offenders go on to be chronic adult recidivists. The group at risk can be identified by early onset and frequency of deviant and delinquent behaviors. This group is associated with impoverished environments, inadequate financial and social resources, family dysfunction, exposure to violent abuse and neglect, genetic loading for psychiatric disorder, and parental criminality. Because of the combination of social disadvantages and externalizing behaviors, this group is difficult to evaluate and treat in normal mental health settings. Court-mandated assessment and treatment offer a unique opportunity to access this high-risk group and provide services not otherwise available. Assessments of severely conduct-disordered children reveal significant levels of co-occurring psychiatric disorders. Thorough assessment to evaluate underlying psychopathology may reveal treatable disorders that may greatly improve general functioning and reduce further recidivism. PMID- 1409033 TI - [Anti-kappa elastin antibody titer in the sera of patients with hyperlipoproteinemia type II, III and IV]. AB - Titre of antibodies against elastin degradation product (kappa-elastin) was measured in patients with atherogenic types of hyperlipoproteinemia. The hemagglutination technique was used. A significant decrease in titres of the tested antibodies was found. It was the most prominent in IIa, III and IIb types of hyperlipoproteinemia and rather mild in IV type. The authors attempted to explain causes of antibodies titres decrease in tested patients and relate their results with those of other authors. PMID- 1409032 TI - [Transient diabetes mellitus with ketoacidosis in a child during the treatment of acute lymphoblastic leukemia with L-asparaginase]. AB - A case of a 11-year girl with the acute lymphoblastic leukemia is presented. Patient was treated with L-asparaginase and developed a transient but lasting several weeks diabetes mellitus with ketoacidosis as a sequelae of this therapy. PMID- 1409034 TI - [Antithrombin III and alpha-2-antiplasmin activities compared with other hemostasis parameters in uncomplicated diabetes mellitus, type 2]. AB - In 40 patients with diabetes mellitus type II without clinical signs of any organ complications and in the respective control group the following indices of hemostasis were assessed: 1) activity of AI-III, 2) activity of alfa-2-AP, 3) fibrinogen, 4) time of fibrinolysis, 5) platelets count, adhesiveness and spontaneous aggregation, 6) kaolin-cephalin and profil stipven-cephalin plasma times. All these indices were normal in uncomplicated diabetes mellitus with the expectation of platelets activity. Stimulation of platelets activity and increase of corresponding parameters appears in diabetes mellitus type II before any other symptoms of angiopathy. PMID- 1409035 TI - [Adaptation reaction to the health resort treatment in patients with diabetes mellitus]. AB - Physical, clinical, biochemical, and functional examinations have been carried out in 70% of patients with diabetes mellitus type 2 treated in health resorts. Patients were treated with diet, drugs, and physiotherapy during a 3-5-week period. It was found, that the whole period of the treatment may be divided into 3 subperiods: period I is characterized by the subjective symptoms produced by the process of adaptation to different environment. This period lasts for 4 days, on average. Periods II and III are characterized by the set of symptoms reflecting a sum of therapeutical physical stimuli. Such symptoms are known in the literature as bath- or spa-reaction. Symptoms of spa-reaction were noted in about 50% of the examined patients. In 21% of them late reaction, i.e. after about 3 weeks, was seen. No worsening of diabetes mellitus was observed during spa-reaction. No correlation between the onset of this reaction and duration of the disease as well as the results of therapy was found. However, spa-reaction was more frequent in the elderly. Period III was followed by the decrease of the symptoms of spa-reaction with marked improvement in glycaemia. Authors' observations lead to some practical conclusions concerning the programs of physiotherapy in dependence on the course of patients' adaptation to the spa. Regulations concerning the routine 24-day treatment period of all patients in health resorts should be revised. PMID- 1409036 TI - [Why are diabetic patients treated at rheumatological hospitals?]. AB - Retrospective analysis included 316 case histories of diabetic patients treated at the Silesian Rheumatology Hospital in 1987-1988. An analysis included causes of disorders, calcium-phosphorus metabolism disturbances, lipid and purine disorders. Statistical parameters were compared with the type of diabetes mellitus, duration of the disease, sex, age and obesity. There were 10% of inflammatory rheumatic disorders (6.4% rheumatic arthritis, 1.7% of rheumatoid spondylosis and 2% of other disorders) in the analysed case histories, and 32% of degenerative disorders (19% of vertebral column joints and 12.7% of other joints). Degenerative disorders were noted more frequently in patients with diabetes mellitus type 2, treated with insulin, while spondylopathies were particularly frequent in female patients of this group. Biochemical disorders in the form of hypocalcemia and hypophosphatemia, hypertriglyceridemia, hyperuricemia, signs of lesions to the liver and kidneys were more increasing with the duration of the disease and the degree of insulin-dependence. Locomotive system disorders are not related only to primary articular lesions. They depend also on diabetic neuro-vascular complications and osteopenia. PMID- 1409037 TI - [Serum N-acetyl-beta-D-glucosaminidase (NAG) activity in patients with diabetes mellitus with reference to diabetic microangiopathy]. AB - In 110 diabetics type I and type II and in 30 control subjects the total serum activity of NAG as well as of its isoenzymatic forms A and B was determined. In cases with diabetic nephropathy the GFR and serum creatinine was also analysed. It was found that NAG activity is correlated to the degree of clinical symptoms of diabetic vascular changes. Therefore it could be suggested that NAG plays a role in development of microangiopathy. NAG determination may also serve as an index differentiating the diabetic microangiopathy from other forms of microvessels. PMID- 1409038 TI - [Profile of the main risk factors of arteriosclerosis in patients with diabetes mellitus]. PMID- 1409039 TI - [Barrett esophagus diagnosed after appendectomy in a patient with diabetes mellitus]. AB - A pathogenetic outline of oesophageal inflammatory lesions with special emphasis on Barrett's oesophagitis has been presented. As recorded in a history of a 65 year old patient at first the stenocardia-mimicking pains occurred a few days after appendectomy. Gastrobulboscopy performed (after coronary insufficiency had been excluded) revealed extensive inflammatory and erosive lesions of the oesophagus and multiple ulcerations of the duodenum. According to the several authors the rapid manifestation of the inflammatory lesions of the oesophagus may be related to the intubation necessary for laparotomy. It may refer particularly to diabetic patients. Control endoscopies showed that a six-week treatment resulted in a total disappearance of mucosal changes. It might be thoughtful to take into consideration a possibility of oesophageal inflammation in clinical differentiation of stenocardia mimicking pains in diabetics who underwent the intubation. PMID- 1409040 TI - [Relative effectiveness of tolbutamide, chlorpropamide and gliclazide]. AB - In clinical practice of hypoglycemic therapy of diabetes mellitus the problem of the optimal selection of oral hypoglycemic agent, corresponding to the individual patterns of regulatory and metabolic disturbances is of primary importance. The individual, pathophysiological basis should be met as much as possible by the pharmacodynamic properties of the selected, hypoglycemic drug. For this reason group of 23 diabetics type II underwent a prolonged, open trial of controlled pharmacotherapy with 4 sulphonylurea derivatives. Pertinent clinical and metabolic parameters were assessed before, during and after planned periods of therapy with Tolbutamide or Chlorpropamide to Gliclazide and Gliclazide to Glibenclamide. In the same time the levels of serum insulin fasting and after breakfast were determined. Also the comparative efficacy of the exchange of the drug in a subgroup of diabetics with fasting glycemia below and above 160 mg% was assessed. It was shown, that the change of Tolbutamide or Chlorpropamide to Gliclazide or Glibenclamide improved the therapeutical effectiveness in general. The individual responses to such a change were however individually differentiated. The change of Tolbutamide or Chlorpropamide to Gliclazide increased the therapeutical efficacy only in these patients, in whom such a change was associated with an increase of prandial, reactive serum insulin level (IRI). In practice they were patients with the fasting glycemia lower than 160 mg%. In patients with fasting glycemia higher than 160 mg% the change of oral compounds under study was not connected with an increase of prandial serum insulin. The metabolic parameters have not improved either. Perhaps they were patients with diabetes mellitus type II, who should be primarily qualified to insulin. PMID- 1409041 TI - [Predicting the development of diabetes mellitus type 1]. PMID- 1409042 TI - [Treatment of dyslipoproteinemia in patients with diabetes mellitus type 2 (non insulin-dependent)]. PMID- 1409043 TI - [Free-radical theory of etiopathogenesis of insulin-dependent diabetes mellitus]. PMID- 1409044 TI - [Proinsulin--its clinical significance]. PMID- 1409045 TI - [Social responsibility of physicians]. PMID- 1409046 TI - [Evaluation of the results of the treatment of children with insulin-dependent diabetes mellitus fully or partially trained in self care]. AB - The study was aimed at assessing the results of diabetes mellitus therapy in 162 children, who underwent 1) the full programme of diabetes education (114 children) and 2) only the part of it (48 children). The first group was under care of Cracow Medical School Pediatrics Institute since the disease and had 2 weeks of formal diabetes mellitus teaching. The second group was treated in a less unified way in different hospitals and did not have the chance of regular teaching programme. The degree of metabolic control was assessed by series of Hb A1c determinations in whole 1987 year. The levels of Hb A1c were also compared with the children age, diabetes mellitus duration and the period elapsing from the time of last teaching. Children who were fully educated in the problems of their disease achieved significantly better results. In all group a deterioration of diabetes control during puberty was however observed. In children not fully educated such a deterioration was also noted in correlation with diabetes mellitus duration. PMID- 1409047 TI - [Notice regarding the results of delayed therapy for atherosclerotic lower limb ischemia in 14 surgical clinics]. PMID- 1409048 TI - [Comparison of early and delayed results of unilateral patency restoration and transplantation in aortoiliac obstruction]. AB - Early and delayed results of the treatment of aortoiliac unilateral incompetence in 144 patients were compared. Eighty seven (60%) patients were treated with aortoiliac prosthesis whereas 57 (40%) with arterial patency restoration. Fifty seven patients of group I reported to the control examination. Favourable effect was found in 47 (82.5%) patients, i.e. in 54% of all operated patients. Thirty six patients of group II reported to the control examination. Favourable effect was noted in 27 (75%) patients, i.e. in 47.4% of all treated patients. Twenty two (25.3%) of patients of group I and 9 (15.8%) of group II died. It was noted also that in 20% of operated patients with unilateral aortoiliac incompetence the disorders in the opposite limb develop despite the type of surgery. Therefore, indications to the implantation of bifurcated prostheses should be extended in some cases. PMID- 1409049 TI - [Delayed results after implantation of bifurcated prosthesis in aorto-iliac incompetence]. AB - Early results and those seen after a 5-year follow up are discussed. Three hundred fifty one patients with aortoiliac incompetence were treated with the implantation of bifurcated aortoiliac prosthesis. Very favourable early result was achieved in 284 (81%) patients. Very favourable delayed effect was noted in 133 patients, i.e. in 75% of patients who reported for the control examination. In the follow up period, amputation of the limb was performed in 30 (8.5%) patients because of progressing ischemia. Hundred thirty seven (39%) followed up patients died during 5 years. Causes of so high mortality rate are discussed in view of risk factors and postoperative complications. PMID- 1409050 TI - [Evaluation of surgical results in lower limb atherosclerotic ischemia comparing men and women]. AB - Multicenter studies involved 1449 male and 131 female patients operated for the atherosclerotic ischemia of the lower limbs. About 50% of all limbs were in the III or IV stage of ischemia (according to Fontaine's classification) before surgery. Atherosclerotic lesions involved mainly aortoiliac segment in the majority of patients. Early results of surgery were similar in both men and women. An improvement during a 5-year follow up period was noted more frequently in women than in men--86% and 68.5% of limbs respectively. Late result of lumbar sympathectomy was similar in both groups. Limb amputation and mortality rates were similar in both groups in the early postoperative period and during a 5-year follow up as well. PMID- 1409051 TI - [Suppurating lesions following surgical treatment of lower limb ischemia due to atherosclerosis]. AB - Patients with suppurative lesions complicating surgical reconstruction of the arteries have been analysed. Such complications have been noted in 110 (102 men and 8 women) out of 311 operated patients. Considering the difference in the number of male and female patients, the risk of suppurative lesions complicating vascular surgery is proportional in both sexes. Thousand three hundred sixty six surgeries included: 361 recanalizations, 944 transplantations, and 61 arterial plasties. Percentage of suppurative complications ranged from 8.8% after transplantations to 9.8% after arterial plasties. More than one surgery has been performed in some patients. The risk of infectious complications has been higher in these patients. Despite antibiotic treatment suppurative infections have been noted in 108 (101 men and 7 women) out of 1244 operated patients, i.e. in 8.6%. Intravenous administration of antibiotics during surgery has proven the most effective prophylaxis. An infection of postoperative wound is the most severe local complication in vascular surgery. It has also been most frequent in the analysed group of patients, being 31.3% of all local complications. PMID- 1409052 TI - [Assessment of late results in surgical treatment of lower limb ischemia in obliterative atheromatosis of the femoral-popliteal region]. AB - The results of treatment of arterial incompetence localized in femoro-popliteal region in the selected 14 centres have been assessed after 24 and 60 months. Eight hundred fifty five patients were operated in the selected centres during 12 months i.e. 50% of all patients operated for obliterative atheromatosis of the lower limbs. Perioperative mortality rate was 4%. During a 5-year follow up, 30% of patients died, and 15% did not return supplied questionnaire, and their fate is unknown. The limb was preserved in 70% of patients operated with any technique except the primary amputation. Markedly worse results were noted in patients operated for necrosis or resting pain and in patients who underwent surgery which did not directly improve blood flow in the affected limb. The authors conclude that the most favourable results are produced by the implantation of vascular prosthesis during the period of intermittent claudication distance shortening before the development of resting pain or necrosis. Such operation are loaded with the lowest rate of failures and complications. PMID- 1409053 TI - [Anticipated results of arterial surgery in chronic atherosclerotic ischemia of the lower limb]. AB - In 1983-1988, the results of conservative and surgical treatment of patients with atherosclerotic ischemia of the lower limbs were assessed with the aid of a questionnaire. A possibility of prognosis was assessed with the use of mathematically processed data obtained with such approach. An effect of clinical symptoms (intermittent claudication distance, resting pain, necrosis) and stage of the disease (duration, K/R index) and risk factors (blood cholesterol, triglycerides, diabetes mellitus, ischemic heart disease, arterial hypertension) on the result of surgical treatment was analysed. The obtained results suggest that clinical symptoms and risk factors may predict the results of surgical treatment in the atherosclerotic ischemia of the lower limbs. PMID- 1409054 TI - [Late results of surgical and conservative treatment for atheromatous ischemia of the lower limb in young patients]. AB - The study was carried out within a multicenter program. Hundred fifty four patients under 40 years were treated (73 conservatively, and 81 surgically) for the atheromatous ischemia of the lower limbs in 14 Departments of Vascular Surgery in Poland within 5 years. The results of the treatment were evaluated according to the site of atheromatous lesions, type of surgery, and mainly according to the progress in pathologic process expressed by the degree of limb ischemia. It was found that surgery performed in the II period of the disease produces the best results. Surgery produces positively better results than conservative treatment in patients with the II period of the disease whereas both surgical and conservative therapy are ineffective in the III and IV degrees of ischemia. Sympathectomy may be effective in the occlusion of crural arteries even of the IV degree ischemia. In case of the II degree ischemia better results are produced by the operation of aorto-iliaco-femoral segment (transplantation or thrombendarterectomy) than that involving distal segment (sympathectomy) whereas the results of conservative therapy are better in peripheral and iliaco-femoral occlusion than those in aortofemoral and multisegmental arterial occlusion. An opinion of several authors on the specificity of atheromatous ischemia of the lower limbs in young patients was not confirmed. PMID- 1409055 TI - [Results of surgical and conservative treatment for multi-level atheromatous arterial occlusion of the lower limb after five years]. AB - After 5 years of observation, materials of 239 patients treated operatively and 96 patients treated conservatively because of multisegmental arterial occlusion of lower limbs were obtained within the framework of multi-central programme of investigation. The results of the treatment with these methods have been evaluated according to the site of the atheromatous changes and the degree of ischemia of lower limbs. It has been ascertained, that after operative therapy, the percentage of good results and the percentage of death in the case of occlusion comprising the aorto-ilio-femoral segment is higher than in the case of occlusion of femoro-popliteal and peripheral segments, whereas in the case of conservative therapy, the situation is reverse. The results of therapy (operative and conservative) of multilevel arterial occlusion, in all kinds of location, depend upon blood supply in the limbs. The results are best (the highest percentage of good results and without improvement, the least number of amputation and death) in the II period of disease and they become worse when the degree of ischemia increases. It appears that the operative therapy is less effective than the conservative therapy in the case of atheromatous multilevel changes manifesting clinically in the form of intermittent claudication, whereas in the case of the IV degree of ischemia, only the operation can save the limb or even the patient's life. PMID- 1409056 TI - [Results of conservative treatment in patients with atheromatous obstruction of arteries in the leg]. AB - Late results of the treatment of 107 patients with crural arteries occlusion (21 (20%) with isolated lesions and 86 (80%) with multisegmental lesions) were evaluated. Favourable result of the conservative treatment was achieved in 38% of patients with isolated lesions, no improvement in 38%, and worsening in one patient were noted during a 5-year follow up. Percentage in the group of patients with multisegmental lesions (including crural arteries) was 23%, 50%, and 27%, respectively. No patients with isolated lesions died during follow up period, whereas 11 (13%) patients with multisegmental lesions died. PMID- 1409057 TI - [Effect of extended anticoagulant therapy on long-term results of bypass for arterial occlusive disease]. AB - Data selected from the questionnaire supplied by the 14 centres of vascular surgery have been analysed. All operated patients have been followed-up for 5 years. An analysis revealed that long-term oral anticoagulant therapy following vascular grafting statistically significantly improved the outcome of surgery in comparison with patients who have not been given oral anticoagulants. There has been no such a relationship, if antiaggregation agents had been used for the treatment. PMID- 1409058 TI - [Long-term results of aorto-iliac occlusive disease treatment with implantation of the Polish vascular prosthesis]. AB - The author analyses distant results of the Polish vascular prostheses implantation to 227 patients with aorto-iliac occlusive disease. Eighty two (29.6%) patients died within 5 years following the operation. Therefore, an analysis of the distant results of therapy included 145 patients. An excellent result was achieved in 20.7% of the treated patients, satisfactory result in 53.9%, no improvement or worsening in 20.7% of cases. Statistically significant relationship between the degree of pre-operative ischemia and outcome of surgery has been noted. Considering blood hypertension, diabetes mellitus, obesity, hypercholesterolemia, and tobacco smoking prior to and after surgery as risk factors, no statistically significant relationship between the distant result of the treatment and the number of risk factor in a single patient has been observed. PMID- 1409059 TI - [Use of the laser for closing a venotomy in an experimental model]. PMID- 1409060 TI - [Surgical treatment of sequelae in thrombotic syndrome in the lower limb]. PMID- 1409061 TI - [Thrombosis and blood platelets]. PMID- 1409062 TI - [Selected medical-legal and ethic-moral problems of collecting tissues and organs for transplantation]. PMID- 1409063 TI - Interactive cytometry, chance or evil of bias? AB - Interactive selection of a limited number of cells in imaging cytometry for determining the DNA histogram of breast cancer cells as the best known prognosticator at the moment, implies statistical and systematic sampling problems. Analysis of histograms of 361 breast cancer aspirate specimens measured in two laboratories demonstrate the expected high statistical variations in view of the only 100 cells measured per case but also slight systematic differences. Controlled systematic sampling without pathological bias results in a somewhat higher malignancy grading than selective biased sampling. For this finding we have no explanation. The main result is, however, that we did not find the expected contrary which makes the argument for at least this application invalid that expert pathologists are needed for reliable interactive sampling. PMID- 1409064 TI - Construction of the knowledge file for an image understanding system. AB - To enable an image understanding system to provide an automated interpretation of diagnostic imagery it must have access to all of the concepts, procedures and methods used by human experts. The paper describes information elicitation from experts of different domains and the construction of a knowledge file. Uncertainty management is based on Bayesian belief network methods. PMID- 1409065 TI - Time dimension in histopathology. AB - In the liver acinus hepatocytes and littoral cells stream from the portal tract toward the terminal hepatic vein. Their average displacement trajectory was denominated as tissue radius. Since cells advance on the tissue radius in one direction, the farther a cell is the older it is, and cell age may be estimated from its position. This property is regarded as time dimension of a tissue. Since distance may be estimated by image cytometry, age determination may be incorporated in the image cytometer software. Distance may be expressed in two types of units: 1. metric e.g. microns, and 2. cell location or the number of cells separating a given cell from tissue origin. Cell age may also be expressed by two units: chronological and biological. Chronological age may be derived from the cell's displacement velocity. A hepatocyte advances daily 2 microns so that a cell at 100 microns distance is 50 days old. Biological age is defined as the cell's location on the radius. Cell location may serve as biological age unit since cells ranked according to their location are also ranked by their ages. The average acinus radius is 22 location long so that in biological age units, maximal hepatocyte life span is 22 locations. One may even say that a cell at location 5 is 2 biological units older than a cell at location 1. In order to estimate chronological age the cell has to be followed for a period of time, while biological age may be read off once from the section. There is yet another advantage for utilizing cell location as unit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409066 TI - An electronic primer in dermatopathology. AB - We present an electronic primer in dermatopathology based on a full-text retrieval system which contains all the features of traditional handbooks of dermatopathology. The system including high-resolution black and white pictures with coloured overlays runs on every personal computer with VGA card and needs no additional software and hardware equipment. The representation of pictures is improved by using high-resolution VGA cards. The system is able to work like an electronic diagnostic consultant in dermatopathology. PMID- 1409067 TI - A computer-based decision support system for diagnostic histopathology of the breast. AB - Accurate histological diagnosis of breast lesions is essential for the appropriate management of the patient. However, the technique of histological typing is problematic due to the large number of histological patterns, often of a complex and variable nature, which occur in breast disease. The introduction of the Breast Screening Programme has increased the burden on pathologists, and emphasised the need for training. Problems arise because mammographic screening detects a greater proportion of special histological types, with their attendant difficulties of identification, when compared to clinically palpable lesions. A computer-based decision support tool has been developed to assist pathologists in the histological diagnosis of breast disease. Unlike conventional expert systems, which seek to recreate the problem-solving processes of an expert, this system has been designed to act as an intelligent assistant to the pathologist. The system represents knowledge in the form of 'disease profiles', and utilises a novel inference model based upon the mathematical technique of hypergraphs. Initial trials with this system have demonstrated that a high level of diagnostic accuracy can be achieved. PMID- 1409068 TI - Development of an automatic program for the stereological estimation of the volume weighted mean volume of cell nuclei. AB - A stereological method was recently developed for the estimation of the volume weighted mean volume of particles from 2D sections. Several authors successfully applied this manual method to paraffin sections of bladder cancers and malignant melanomas and found a good correlation between the mean nuclear volume and the histological grading and prognosis of these tumors. The implementation of this measuring method on an automatic image analyser, devoted to routine work in tumor pathology, is presented. The accuracy of the automatic measurement has been evaluated together with the first results obtained from human esophageal cancers. PMID- 1409069 TI - MIPSY: real-time morphometry to quantify the time course of rapid epithelial restitution. AB - The gastrointestinal mucosa has the ability to repair itself rapidly following superficial mucosal injury by rapid epithelial restitution. The mechanism consists of cell migration and does not involve mitosis. This study reports the mechanisms of rapid epithelial restitution in the rabbit colon in vivo and in the human colon in vitro, describes a new computerized real-time morphometry system to investigate the time course of restitution and presents a new method to calculate the migration speed of epithelia during the repair process. Superficial mucosal damage to the rabbit colon in vivo was produced by luminal exposure to 100 mM HCl for 5 min (80% of mucosal surface), a comparable injury in the human colon in vitro was obtained by luminal exposure to 10 mM HCl for 10 min (96% of mucosal surface). After detachment of the damaged tissue the intact epithelial cells in the vicinity of the necrosis extended pseudopodia and migrated over the denuded basal lamina. The morphological appearance of rapid epithelial restitution was the same in the rabbit and the human, only the time course was postponed in the human. The time course of rapid restitution was assessed by a newly developed computerized morphometry system (MIPSY). When tissues were examined after various time points following acid damage, 61% of the mucosa were damaged in the rabbit after 1 h, 10% after 2 hs and 20% after 5 hs. In the human colon 85% of the mucosal surface were damaged after 2 hs and 20% 5 hs after the end of acid exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409070 TI - Cell contour extraction on multi-threshold images. AB - A procedure for the extraction of cell and nuclear contours from digital images is presented. The procedure is simple and suitable for efficient implementation in an interactive environment where the user selects a region of interest containing the cell to be segmented. Segmentation is facilitated by multi thresholding where the threshold values are determined by an iterative algorithm using the mean square error criteria to cluster the image pixel values. Edges are detected on the threshold images by employing a binary morphological filter and the desired contours are selected by considering closed contours in the edge image. The cell region is first extracted by performing segmentation, edge detection and contour extraction on the region of interest. The nuclear region is subsequently extracted by reapplication of the algorithms within the extracted cell region. Segmentation examples are presented. PMID- 1409071 TI - Evolutionary somatic cell changes in cervical tumour progression quantitatively evaluated with morphological, histochemical and kinetic parameters. AB - The somatic cell changes which characterise malignancy evolution in human cervical preneoplastic and neoplastic lesions have been assessed on histological sections by means of a computerised image analyser. Many features have been simultaneously measured on each cell of the lesions studied, and the following results have been obtained: Some features, mainly kinetic, show continuously increasing values which express changes correlated to the increasing malignancy; other features, especially related to nuclear atypia, cellular heterogeneity and the degree of aneuploidy, have values dropping at the level of early stromal infiltration, which can be morphometrically characterised as composed of relatively homogeneous phenotypes; these features seem to express the degree of genetic instability and relate to the evolutionary somatic cell changes; tumour progression evolves through sequential discontinuous steps, each of them characterised by specific phenotypical features of the neoplastic cell population; the neoplastic cells in the foci of early stromal infiltration and vascular invasion, phenotypically more homogeneous than the parent cell populations of carcinoma in situ and infiltrating carcinoma, seem to possess a greater genetic stability. PMID- 1409072 TI - A simplified histoscore for the estrogen receptor assay in breast cancer. AB - Different histoscores combining the number of positive cells and the intensity of staining have been used to evaluate the estrogen receptor immunocytochemical assay (ER-ICA). Our aim was to investigate if the simple estimation of the amount of positive cells could be sufficient for the semiquantitative analysis of ER ICA. Tissue from 51 women with ductal breast carcinoma was used. Half of each sample was processed with the quantitative assay (ER-EIA) and the other half with ER-ICA. Microscopical analysis was performed by two independent observers and classified on a simple scale from 0 to 4+. With EIA 31 cases (60.78%) were positive and 20 (39.21%) negative. With ER-ICA 29 (56.86%) had immunostaining, whereas 22 (43.13%) did not. 95.83% of the ER-ICA positive cases and 77.7% of ER ICA negative had a good correlation with EIA values. Statistical analysis showed a high degree of correlation (r = 0.88 p 0.001). Hence, simple semiquantitative estimation in ER-ICA is sufficient to provide useful information for clinical use about ER content in tissue sections. PMID- 1409073 TI - An image cytometric DNA-analysis in breast neoplasms. Parameters of DNA aneuploidy and their relationship with conventional prognostic factors. AB - In this prospective study, an image cytometric DNA-analysis was performed in 86 women with breast neoplasms (72 primary invasive carcinomas and 14 benign lesions). Four DNA ploidy parameters were analysed: histogram type (according to AUER classification), DNA-index, tumor cells with DNA content above the 5n limit and DNA malignancy grade (DNA-MG, calculation according to Bocking). Their correlations with well established prognostic factors in breast carcinomas (tumor size, lymph node status, histologic grade, hormone receptor content) were studied. All but one benign lesions were diploid (13/14 cases), whereas the majority of the primary invasive breast carcinomas were aneuploid (58/72 cases). A predominance of carcinomas with a percentage of cells superior or equal to 1% with DNA content above the 5n limit was observed (54 cases out of 58). Most of the aneuploid tumors had a histogram type III or IV (53 cases) or a high DNA index (50 cases). Of these 58 aneuploid cases, only 26 tumors had a DNA-MG superior to 1. Interestingly, 26 tumors had the 4 criteria of aneuploidy, 19 had 3 and 9 had 2 and only 4 tumors had one parameter. The DNA-MG was significantly related to hormonal receptors (p less than 0.001) and tumor size (p less than 0.01). The histogram types (Auer classification) and the DNA content above the 5n limit were correlated with histologic grade (SBR or SBRM) (p less than 0.02). Concerning the DNA-index no correlation was observed with well established prognostic factors. On the other hand no significant correlation was found between these new biologic variables and lymph node status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409074 TI - Two types of endometrial papillary neoplasm. A morphometric study. AB - Fourteen cases of Papillary Endometrial Carcinoma (EC) were analyzed by Interactive Computerized Morphometry. Seven cases were diagnosed as well differentiated adenocarcinomas with papillary features (PF) and belonged to a group of EC with associated adenomatous hyperplasia (AH). Seven cases were diagnosed as uterine papillary serous carcinomas (PA) and belonged to a group of EC without associated AH. Two morphometric procedures were used. DRAW for the characterization of individual nuclei (area, perimeter, chord) and NU-MEAS for tissue architectural features (crowding and stratification). Using a stepwise discriminant multifactorial analysis, both methods proved to be accurate for the two diagnostic categories, as shown by the 100% posterior probabilities and by the two diagnostic categories, as shown by the 100% posterior probabilities and by the distances between group means. A doubtful case was analyzed and classified using a K-nearest neighbor procedure, compared to the individual case in the database. The distinction between the two types of papillary EC is important for the differential diagnosis of the two lesions. Well differentiated adenocarcinoma with papillary features is seen usually in the context of a well-differentiated adenocarcinoma, in a group of patients known to have estrogen-related less aggressive tumors. Uterine papillary serous carcinoma was described to have a biological behavior similar to that of papillary ovarian carcinoma and is encountered in a group of patients with more invasive and less differentiated EC2. Computerized interactive morphometry is a valuable method to use for the accuracy of this differential diagnosis in doubtful cases. PMID- 1409075 TI - Densitometric and morphometric study of immunocytochemical estrogen receptors detection in breast carcinomas. AB - Immunohistochemical quantitative evaluation of estrogen receptors (ER) detected in tissue sections from 30 breast tumors by monoclonal antibody was performed using a densitometric method. In particular, ER concentration was calculated by nuclear mean optical density (nMOD), while heterogeneity in ER content was calculated by the coefficient of variation (CV) of the nuclear optical density histogram. Tumors which showed more than 60% of positive cells had a mean value of ER-nMOD of 0.116 +/- 0.002 a.u. and of ER-CV of 33.74 +/- 0.68. Tumors which showed 30% to 60% of positive cells had a mean value of ER-nMOD of 0.082 +/- 0.006 a.u. (arbitrary units) and of ER-CV of 36.25 +/- 3.44. Tumors showing less than 30% of positive cells had ER-nMOD of 0.052 +/- 0.009 a.u. and ER-CV of 48.49 +/- 5.61. These results indicate that the greater the concentration the lower the ER heterogeneity within the tumor sample. No significant differences between ER ICA results, nuclear size and form factors were found. PMID- 1409076 TI - Immunohistological quantitative analysis of S100 protein-positive cells in T-cell malignant lymphomas, especially in adult T-cell leukemia/lymphomas. AB - S100 protein-positive cells (S100+ cells) in 36 cases of T-cell lymphoma (T-ML) in the lymph node and 15 cases of T-ML in the skin were analyzed immunohistologically in order to study their quantitative features in adult T cell leukemia/lymphoma (ATLL). The T-MLs were categorized according to the updated Kiel classification, and the T-cell pleomorphic type (Pleo) was subcategorized into 3 subtypes: Pleo-ATLL, Pleo-clear and Pleo-others. The population of S100+ cells and the first to fifth minimal distances of every S100+ cell were measured on micrographs of paraffin sections that had reacted to anti S100 protein antibody according to the ABC method. Lymphoblastic and chronic lymphocytic leukemia types showed low populations of S100+ cells and long values of the first minimal distance. T-zone lymphoma without follicles and angioimmunoblastic lymphadenopathy with dysproteinemia-type T-ML had high populations and low values of the first minimal distance. Among the three subtypes of Pleo in the lymph node, Pleo-ATLL gave the highest population and the shortest value of the first minimal distance of S100+ cells, but this trend was not found in the skin. Clusters of more than five S100+ cells were more common in the Pleo-ATLL subtype than in the other two subtypes. The increase and clustering of S100+ cells in Pleo-ATLL suggests that the lymphoma cells act on S100+ cells as a helper.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409077 TI - Comparative quantitative study of Ki-67 antibody staining in 78 B and T cell malignant lymphoma (ML) using two image analyser systems. AB - Total Ki-67 stained area percentage was studied in 32 B and 46 T malignant lymphomas (ML) using two different image analyser systems (TAS, Leitz; SAMBA TM 2005, TITN) respectively. The total Ki-67 area percentage was highly correlated to the number of Ki-67 positive cellular profiles (B-ML, r = 0.93; T-ML, r = 0.88), indicating that area percentage is a reliable alternative method to the manual cell counting. Image analysis allows quicker measurements, appropriate to large and strictly lymphomatous regions. The cell image processor (SAMBA TM 2005, TITN) linked to a color video camera was more suitable for immunohistochemical sections and allowed more automated and faster measurements than the texture analyser (TAS, Leitz) linked with a black and white camera. Alkaline phosphatase technique with fast red as chromogen was more suitable for the detection of Ki-67 stained area by thresholding than peroxidase technique with aminoethylcarbazol or with diaminobenzidine as chromogens. Significant differences were found between low and high grade in B and T ML according to the Kiel classification (mean values +/- SD of 7.7 +/- 3.8% and 16.6 +/- 6.2% in B-ML and of 10.2 +/- 7.9% and 25.6 +/- 16.3% in T-ML respectively). In follicular B-ML, considering follicular areas only, values were comparable to high grade ML; angioimmunoblastic lymphadenopathy-like (AILD-type) T-ML belonging to low grade ML showed similar values to pleomorphic T-ML with medium and/or large cells belonging to high grade ML.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409078 TI - Nuclear DNA density of parathyroid lesions. AB - Nuclear DNA density analysis was carried out on six normal control human parathyroid glands and forty-six pathological lesions of human parathyroid tissue. The pathological glands had originally been classified as twenty hyperplasias, twenty-one adenomas, and five carcinomas in accordance with clinical-pathological information. Specimens had been obtained through the Surgical Pathology Department of the University Hospital, London, in the form of either imprints from the cut surface of a lesion, or as cell separation samples from a paraffin block. Nuclear DNA ploidy analysis of the normal glands showed, as expected, a diploid cell population. Sixty-one percent of nuclei of the carcinomas were above 2C, extending to 7C. There was a significant difference in nuclear DNA content between normal and benign tissue versus tissue classified as carcinoma. No significant difference in nuclear DNA ploidy could be established between the benign adenoma and hyperplasia tissue; however, marked significant DNA ploidy differences were found between tissue from the latter two and carcinoma. DNA ploidy from cell image analysis using Feulgen's reaction can be useful in establishing a differential diagnosis between carcinoma and benign lesions. PMID- 1409079 TI - Nuclear morphometry of primary B cell thyroid lymphoma. AB - Thyroid lymphoma is usually distinguished from anaplastic thyroid carcinoma and from Hashimoto's thyroiditis by morphological and immunohistochemical assessment of tissue sections. Our objective was to assess the value of nuclear morphometry in the differential diagnosis of these conditions. Nuclear area measurements were performed on 10 cases of thyroid lymphoma using an IBAS 2000 Image Analyser and compared with similar measurements performed on 10 cases of Hashimoto's thyroiditis and 2 of anaplastic thyroid carcinoma. It was found that karyometry demonstrated differences between all three conditions, the cases of thyroiditis being distinguishable from lymphoma on the basis of mean nuclear area alone. Mean nuclear area for lymphomas was greater than for Hashimoto's thyroiditis and lower than for anaplastic carcinomas. The mean nuclear area also reflected the grade of lymphoma, with the exception of one case which had a large reactive T cell population. It is concluded that nuclear morphometry provides valuable information in the diagnosis and assessment of thyroid lymphomas. PMID- 1409080 TI - Cytologic diagnosis of non-oxyphil follicular neoplasias of the thyroid. Multivariate classification procedure based on quantitative nucleolar features. AB - The study was done on cytologic material of 58 non-oxyphil follicular neoplasias of the thyroid, 32 of which were adenomas and 26 carcinomas. Three groups of nucleolar features were quantified using a routine microscope with an ocular micrometer: frequency-, size-, and margination-related features. Since value overlap was present between two categories for all the variables, stepwise discriminant analysis was applied. The following three features were selected by the computer for calculation of one canonical discriminant function: percentage of marginated nucleoli, percentage of nuclei with one nucleolus, mean major nucleolar diameter. The percentage of agreement between morphologic and computer classifications was 95%. Two follicular adenomas were allocated to the carcinoma category, whereas one follicular carcinoma was allocated to the adenoma category. Out of 58, 52 were diagnosed by the computer into one of the two diagnostic categories with a very high probability, i.e. P greater than 0.75, the remaining 6 being considered intermediate. PMID- 1409081 TI - Prognostic factors in squamous cell carcinoma of the oral cavity. A retrospective study of 80 cases. AB - A multiparameter analysis of 80 squamous cell carcinomas of the oral cavity was performed to determine the relative prognostic weight of the location of the tumor, tumor size (T), microscopic grade (G) and DNA content measured by means of flow cytometry. Tumors of the lip have an invariably favourable outcome, while at the other locations they have high rates of mortality (total 5 years of survival less than 35%). A simple statistical analysis was performed using the concepts of death sensitivity (DS), death specificity (DSp), life sensitivity (LS) and life specificity (LSp): the best measure of unfavourable outcome was represented by G3 (DS = 0.69; DSp = 1) and by DNA aneuploidy (DS = 0.76; DSp = 0.45), while the best measure of favourable outcome was represented by G1 (LS = 0.53; LSp = 0.96), T1 (LS = 0.81; LSp = 0.78) and by DNA diploidy of the tumor cells (LS = 0.45; LSp = 0.86). A survival analysis using a step by step regression model according to Cox was carried out in order to evaluate more precisely the relative importance of prognostic factors: traditional prognostic factors (histological grade = G and tumor size = T) showed a strong statistical significance, while DNA content added some additional prognostic information only if associated to the macroscopic features of the tumor. PMID- 1409082 TI - Laryngeal intraepithelial neoplasia (LIN). An analytical morphometric approach. AB - Laryngeal Intraepithelial Neoplasia (LIN) is graded in 3 levels (LIN Grade I-II III), corresponding to the classic aspects of mild, moderate and severe dysplasia in situ carcinoma, on the basis of the number and position of mitoses and of the undifferentiated or atypical cells limited to the basal or extended to the intermediate or the superficial layers of epithelium. In order to reduce the subjective imprecision of these parameters we have applied not only traditional dimensional evaluators but also procedures of analytical morphometry to the nuclear shape. By using the software system S.A.M. (Shape Analytical Morphometry) we have examined fifty nuclei of the basal layer in LIN grade I, II and III, fifty nuclei in normal laryngeal mucosa and fifty nuclei in invasive carcinoma of the larynx (twenty-five cases in all). Normal and dysplastic nuclei did not show any dimensional differences, while the carcinomatous nuclei were significantly larger. An asymmetric distortion of the nuclear contour was noted in the moderate and severe dysplasia, but not in carcinomatous cells. Also the Fourier parameters, increased in severe dysplasia, decreased dramatically in carcinomatous cells which showed nuclei with minor contour irregularities than the normal cells. These findings outline the discriminative power of the analytical morphometry and suggest a possible correlation between nuclear shape and cell biology. PMID- 1409083 TI - Quantitative histopathological evaluation of vocal cord dysplasia with particular emphasis on nuclear orientation. AB - We have applied morphometry on formaldehyde-fixed, H & E-stained diagnostic laryngeal biopsies from 7 patients with mild dysplasia and 7 with severe dysplasia/carcinoma in situ, in search of objective parameters required for reproducible histopathological grading of epithelial dysplasias. Special emphasis has been put upon the individual nuclear polarity as a spatial variable. Also included were 4 specimens with normal epithelium. By means of a semiautomatic digitizing tablet, the nuclear and epithelial area, formfactor and the polarity variation between the longitudinal axes of adjacent nuclei were measured in the basal, parabasal, middle and luminal layers of the epithelium. N:C-ratio, mean values of nuclear area, formfactor or their coefficient of variation could not distinguish between mild and severe dysplasia. The variations in neighboring nuclear polarity, however, revealed a highly significant distinction between mild and severe dysplasia (p less than 0.001). This parameter may therefore have diagnostic potential. PMID- 1409084 TI - Quantitative analysis of nucleoli and nucleolar organizer regions in cultured primary human normal, reactive and malignant mesothelial cells. AB - The number and the size of silver-stained intranuclear granules, which correspond to the nucleolus and nucleolar organizer regions, have been determined by means of quantitative methods in cultured primary human mesothelial cells obtained from normal, reactive and malignant mesothelium. The mean values per nucleus of the number, the total area, the average area, and the relative area of the silver stained granules and the mean nuclear area were determined for each of the three conditions. Normal, reactive and malignant mesothelial cells differed significantly in all the features. These findings at the optical level reflect the differing rate of the nucleolar biosynthetic activity related to the different biological properties of the three cell types, and the features can be useful morphometric descriptors in the diagnostic pathology of the mesothelium. PMID- 1409085 TI - Evaluation of AgNOR count in distinguishing benign from malignant mesothelial cells in pleural fluids. AB - The authors have evaluated in eight reactive and eight malignant pleural effusions the number of intranuclear dots representing the nucleolar associated proteins stained with silver colloid technique (interphase nucleolar organizer regions-AgNORs). The mean number per nucleus in benign reactive effusions was 1.56 (SD 0.77) while in mesotheliomatous effusions it was 2.81 (SD 1.44). The statistical analysis of values, by Mann-Whitney U Wilcoxon Rank Sum W Test, revealed a significant difference of AgNOR counts in the two cytological samples. The variability of AgNOR areas and morphologies in reactive and mesotheliomatous nuclei in pleural fluids is evaluated applying automatic image analysis. PMID- 1409086 TI - Intra-tumor DNA ploidy distribution pattern and its relation to histologic type in gastric carcinoma. AB - The pattern of intra-tumor DNA ploidy distribution was analyzed in stepwise sections in 64 cases of surgically resected gastric carcinoma. Five varying patterns were identified: Type A comprised only diploidy in all stepwise sections, Type B comprised only aneuploidy with the same DNA Index(DI), Type C comprised diploidy in the great majority of sections with aneuploidy in some parts, Type D comprised aneuploidy in the great majority of sections with diploidy in some parts and Type E comprised only aneuploidy, but with varying DI. These 5 patterns could be grouped into 2 categories; predominantly diploid (Types A and C) and predominantly aneuploid (Types B, D and E). The former category included 34 cases (12 differentiated carcinomas) while the latter included 30 cases (22 differentiated carcinomas). Thus, a statistically significant correlation was detected between the histologic type and the intra-tumor DNA ploidy distribution pattern; in the majority of cases, differentiated carcinoma exhibited predominantly aneuploidy, while undifferentiated carcinoma exhibited predominantly diploidy (p less than 0.01). This tendency was the same for all depths of invasion, except for submucosal carcinomas which exhibited predominantly diploidy. PMID- 1409087 TI - Epithelial dysplasia of the gastric mucosa. A morphometric and ploidy pattern study. AB - 60 cases of gastric dysplasia (20 mild, 20 moderate and 20 severe) were quantitatively studied and compared with cases of hyperplastic polyp (No 10), intestinal metaplasia (No 20), peptic ulcer (No 10) and invasive adenocarcinoma (No 20). In each case the area, the perimeter and the integrated optical density of 100 nuclei were measured in Feulgen stained tissue sections by means of a Leitz TAS. The stepwise discriminant analysis demonstrates that severe dysplasia and adenocarcinoma can be well distinguished from mild and moderate dysplasia. The ploidy pattern study demonstrates that the presence of severe dysplastic changes corresponds to a sharp increase in the degree of aneuploidy. In peptic ulcer, intermediate values between "benign" and "malignant" lesions were found. PMID- 1409088 TI - Cytometry in histological sections of colon carcinoma. AB - A short description of a project of cytometry in histological sections of colon carcinoma is given with emphasis on the methodical aspects. Possible strategies of cytometric measurement and problems related to it (focus, overlap, segmentation of objects) are described. The main effort concerns interactive selection of tumor cells and the segmentation in cases of densely distributed and overlapping nuclei. All other succeeding processing steps are performed fully automatically. The resulting quantitative features are stored together with the original images on an optical disk for further examinations and reexaminations, allowing the direct relation of feature values to visual image content. The evaluation of the features as well as their interpretation is only at the beginning. Especially the problem of relating section information with true 3 dimensional information is not described here and necessitates further research. In a first investigation only a few tumors without and with metastases were analyzed. The preliminary results correspond with findings of Kunze et al. PMID- 1409089 TI - Quantitative study of the precancerous and malignant lesions in colorectal adenomas. AB - 150 endoscopically removed colorectal adenomas are quantitatively studied. In 90 cases dysplastic glands constituted the entire lesion (30 mild, 30 moderate, 30 severe); in 60 cases foci of adenocarcinoma were present (30 intramucosal, 30 submucosal). In each case the area, the perimeter and the integrated optical density of 100 nuclei were measured from Feulgen-stained paraffin sections. The results show a continuous neoplastic progression in the trends of the morphometric parameters as well as in the ploidy pattern. The stepwise discriminant analysis defined the morphometric features of the atypical nuclei, which were present in small numbers also in mild dysplasia; they progressively increased in number, reaching the maximum in submucosal carcinoma. PMID- 1409090 TI - Texture analysis of histological images of giant cell tumor of bone. AB - To gain an objective evaluation of histological sections of giant cell tumors of bone (GCT) and osteosarcomas, microscopic pictures were taken and their grey-tone image measured, using a flying spot scanner and computer. Various values of eight parameters expressing certain characteristical brightness distribution patterns were computed, and comparatively examined among the three groups of benign GCT, malignant GCT and osteosarcoma. As a result, some parameters could facilitate differentiation between the histological images of these bone tumors. Especially, "angular second moment (ASM)", "Contrast" and "Coefficient of variation (COV)" were useful even for discrimination between malignant and benign GCT. After factor analysis of the values of these parameters, scores of each factor for a number of histological scene images were plotted on a 2-dimensional factor plane. On this plane, which was considered to be a histological feature plane, cases of benign GCT were separated from those of osteosarcoma. Cases of malignant GCT were distributed between the two groups. These results suggest that this method could be valuable for computer evaluation of histological images of benign GCT and osteosarcomas. PMID- 1409091 TI - Morphometric analysis of cartilaginous tumors. AB - 144 chondromas and chondrosarcomas have been investigated. Morphometry has been performed: the relative volume density of tumor cell nuclei (Vv%n) and the nuclear area have been measured. The results show that the relative volume density of nuclei is a useful parameter, regarding the localisation of the tumors, to discriminate chondromas and chondrosarcomas, while the nuclear area is no safe criterion to separate these entities. PMID- 1409092 TI - Morphometrical investigation of medulloblastoma nuclei by S.A.M. (Shape Analytical Morphometry) software system. AB - In order to characterize medulloblastomas and to get over the difficulties sometimes encountered in differential diagnosis, a double morphometric procedure has been applied to its nuclei. The first consisted of size measurements (maximum diameter, area and perimeter), the latter is represented by S.A.M. (Shape Analytical Morphometry) software-system specifically implemented to describe shape of biological structure by analytical parameters. Analytical and dimensional parameters submitted to Hotelling's multivariate discriminant analysis gave the best results when used together in convenient discriminant subsets, thereby allowing a good distinction between medulloblastoma in comparison with neuroblastoma, Ewing's tumor, lymphoblastic and lymphocytic lymphoma. These results underline the usefulness of morphometric characterization also for practical diagnostic purposes. PMID- 1409093 TI - Significance of variation in DNA flow cytometric analyses from paraffin-embedded breast cancers. Evaluation of the grading efficiency of ploidy determination, DNA index, and S-phase fraction. AB - 116 paraffin-embedded breast cancer samples were analyzed by flow cytometry. From each sample 3 consecutive 50 microns sections were cut for the study. The presence of neoplastic tissue was verified from light microscope sections cut before and after the adjacent sections. One laboratory started with one section from each block and was allowed extra sections when needed for analysis. At the end the laboratory obtained results from all 116 cases. The rest of the samples were studied by 2 other laboratories. Samples with results from 2 or 3 laboratories then allowed variability analysis and the estimation of the grading efficiency in a 2-grade system. Inconsistency in diploidy/aneuploidy distinction was present in 36 of 111 (32.4%) cases studied by two or three laboratories. This inconsistency was less obvious in samples graded as multiploid by at least one of the laboratories. The grading efficiency as analyzed from the results of 3 laboratories was 0.89, and of 2 laboratories, 0.84. The DNA index showed a slightly higher grading efficiency. At the cutoff point of 1.3, 91% of cases could be expected to be correctly classified into low ploidy and high ploidy groups (grading efficiency 0.91). The S-phase fraction had a mean grading efficiency of 0.89, a performance comparable to that of diploidy/aneuploidy distinction. In the light of the available data the flow cytometric analysis can add to the consistency of grading, especially when compared with subjective histological grading. However, the data do not suggest that flow cytometric analysis of paraffin sections as a grading method would be more consistent than quantitative histopathology from sections. PMID- 1409094 TI - Biological image analysis for microscopical diagnosis: the work-station S.A.M. (Shape Analytical Morphometry). AB - The S.A.M. (Shape Analytical Morphometry) software system and its related work station give a generalized and easy-to-handle tool to face a classic and intriguing problem in biomedical morphological diagnosis. What is the shape of an object in a microscopic image? How can we understand the relationship between size and shape? According to Holloway: "Measurements such as length, width, height, whether in chords or arcs only describe space, ... and further run into the abyss of allometric correction ... if additional information (shape?) to size is expected, some method of allometric correction must be used." The S.A.M. software system assumes a logic architecture able to separate and to parametrize independently shape characteristics in terms of allometry and local pertubation by analytical procedures (polynomials, parabolic fitting, Fourier analysis) in addition to the classic evaluations of size and density carried out by image analyzers for microscopical diagnosis. PMID- 1409095 TI - Silver-stained nucleolar organizer proteins in urothelial bladder lesions. A morphometric study. AB - The diagnostic value of image analysis of silver-stained nucleolar organizer regions (AgNORs) has been investigated in 170 urothelial bladder lesions obtained by transurethral biopsies in the same number of patients. According to the WHO classification 25 specimens showed a flat non-invasive growth pattern with simple hyperplasia or mild dysplasia (H/D1 = 10), as well as moderate (D2 = 10) to severe atypia (Cis = 5). 135 samples were of papillary and/or infiltrating type including polypoid cystitis (pC = 5), true papillomas (G0 = 7), and carcinomas of different malignancy grade (G1 = 30, G2 = 55, G3 = 38). 10 biopsies served as normal controls. Benign non-neoplastic urothelium (controls, H/D1, pC) exhibited few but large AgNORs (mean number [MNN] = 3.3 +/- 0.5, mean area [MNA] = 0.29 +/- 0.08 micron 2), whereas carcinomatous lesions (Cis, G1-G3) showed numerous small silver-stained dots within their nuclei (MNN = 6.9 +/- 1.1; MNA = 0.12 +/- 0.04 micron 2). Both parameters, MNN and MNA, were inversely correlated (r = -0.69, p less than 0.001); their quotient (NQ = MNN/MNA) revealed a clear cut difference in the AgNOR content of benign (control, H/D1:NQ = 12.8 +/- 2.5) and moderate to severe atypical flat urothelial lesions (D2, Cis: NQ = 44.2 +/- 12.8, p less than 0.001). This parameter also discriminated between G1 (NQ = 40.7 +/- 17.3), G2 (NQ = 57.5 +/- 18.8), and G3 carcinomas (NQ = 79.0 +/- 21.8, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409096 TI - Quantitative immunohistologic study of lip biopsies. Evaluation of diagnostic and prognostic value in Sjogren's syndrome. AB - In a group of 45 patients with Sjogren's syndrome (SS) and 80 controls the high specificity (95%) and sensitivity (100%) of a recently proposed bivariate quantitative immunohistologic (QIH) criterion for SS, based on percentages of IgA and IgG-containing plasma cells in labial salivary gland (LSG) tissue, was confirmed. The best univariate QIH criterion for discrimination between LSG biopsies of SS patients and controls appeared to be based on the percentage of IgA containing plasma cells, and had a specificity of 99% and a sensitivity of 96%. A criterion based only on the percentages of IgM-containing plasma cells, proposed in another recent study, resulted in a high number (31%) of false negatives. Interobserver reproducibility of QIH diagnoses was excellent. Moreover it was demonstrated that accuracy, precision and the interobserver reproducibility of plasma cell counting depends on the choice of tissue fixation and immunohistologic staining procedure. The combination of formol sublimate fixation and peroxidase anti-peroxidase procedure appeared to be the best combination for QIH examination. Furthermore, in 2 SS patients systemic monoclonal IgM/kappa gammopathy was preceded by high predominance of IgM and kappa containing plasma cells in the plasma cellular infiltrate of the LSG tissue. PMID- 1409097 TI - Quantitative analysis of quadriceps muscle biopsy in systemic sclerosis. AB - The lesser diameter of the fibers, separately of type 1 and type 2 fibers, and the capillary density evaluated as number of capillaries/area and number of capillaries/fiber were quantitatively estimated in muscle biopsies from 12 patients with systemic sclerosis. Nine patients with polymyositis or rheumatoid arthritis and six patients with muscle dystrophy and neurogenic atrophy served as controls. The results showed that patients with systemic sclerosis had low values of the lesser diameter of the fibers. This reduction was most obvious in type 2 fibers. The capillaries were also significantly reduced when compared with the control groups. When considering the capillaries/fiber ratio, seven out of eight patients with values lower than 0.7 belonged to the systemic sclerosis group. In systemic sclerosis the capillary density values were not significantly correlated with those of the lesser diameters of the fibers. PMID- 1409098 TI - Enlargement of synaptic size as a compensative reaction in aging and dementia. AB - A quantitative investigation has been carried out on synaptic contact zones of dentate gyrus supragranular layer and cerebellar glomeruli in autoptic samples from adult, old and demented patients. During physiological aging and senile dementia, the synaptic average area was significantly increased as compared to adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. Current literature reports that, in animal models, enlarged synapses undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the reduction in number and in total contact area of the synaptic junctions. PMID- 1409099 TI - The value of simple morphometric techniques in the diagnosis of osteoporosis. AB - In order to assess the value of simple morphometric methods in the diagnosis of osteoporosis we measured trabecular bone volume (TBV), trabecular number per unit area and relative osteoid volume in two separate iliac crest biopsies in 20 patients with conclusive autopsy evidence of osteoporosis and 20 controls. In osteoporotic patients trabecular bone volume ranged between 3.0-19.2% (median 10.7%) in the anterior and 3.0-14.3% (median 9.7%) in the posterior biopsy and in controls between 2.5-24.8% (median 13.5%) in the anterior and 5.8-25% (median 12.4%) in the posterior. Trabecular numbers in osteoporotic patients ranged from 1.7-8.3/10 mm2 (median 3.5) and in controls 1.6-17/10 mm2 (median 5.63). Relative osteoid volume showed a similarly wide range. In adjacent biopsies trabecular bone volume and trabecular number could differ by as much as 100% and this casts doubt on the value of sequential bone biopsies in the management of individual patients. We conclude that simple morphometric techniques cannot accurately diagnose osteoporosis. However, if the TBV is greater than 18% osteoporosis is unlikely to be present (upper 95% confidence limit = 17.8%). However, a low value for TBV is not diagnostic for osteoporosis because of a large overlap between control and osteoporotic groups. PMID- 1409100 TI - Osteologic standardization of human coxarthrosis using histomorphometry and its relevance for HIP alloarthroplasty. AB - Using bone histomorphometry, in this study the osteologic status of 107 patients with coxarthrosis and femoral neck fracture [FNF] was assessed and compared with bone parameters from patients revised for aseptic loosening. Bone biopsies of the acetabulum and the proximal femur from patients with primary coxarthrosis [pCoxA] (69), dysplastic coxarthrosis [CDH] (19), rheumatoid arthritis [RA] (9), femoral head necrosis [FHN] (8), femoral neck fracture [FNF] (4) and aseptic loosening (12) were taken during hip alloarthroplastic surgery, prepared undecalcified and analysed using histomorphometry (according to MERZ). In pCoxA the following average figures of bone parameters of the acetabular biopsy were determined: trabecular bone volume (TBV) 39.6%, osteoid volume (OV) 3.9%, active osteoblastic surface (AOS) 6.5%, osteoclastic resorption surface (ORS) 2.4%, osteoid surface (OS) 17.4% and resorption surface (RS) 7.0%. As average figures of the femoral biopsy in pCoxA were assessed: TBV = 17.2%, OV = 1.3%, AOS = 0.9%, ORS = 0.4%, OS = 6.5% and RS = 2.5%. These data were compared with bone parameters of secondary coxarthrosis, osteoporosis (FNF) and aseptic loosening. Based on the study of Oettmeier et al. on femoral heads (Skel Radiol 18: 165-174, 1989), the investigated groups were subdivided into three osteologic types of the hip. The osteopenic type was found in 10% of pCoxA, 43% of RA and 28% of CDH. The hyperostotic type, predominantly occurring in males, was mostly demarcated in FHN (38%) and pCoxA (12%). The results demonstrate the individual osteologic status of patients before hip alloarthroplasty. This could influence planning of the operation and the bone-implant interface as well as long-term prognosis of artificial joints. PMID- 1409101 TI - Macrophage and epithelioid cell nuclear morphology in leprosy. AB - The spectrum of disease in leprosy is characterised by the presence of macrophages in lepromatous lesions and epithelioid cells in tuberculoid granulomas. Since changes in nuclear shape occur during macrophage activation, we have measured nuclear morphology by planimetry in biopsies across the leprosy spectrum. The results show no significant correlation of any of the parameters of nuclear morphology measured between different lesions or between biopsies from the centre and edge of the same lesion. There were no differences between the Ridley-Jopling groups. However, several parameters which measure the degree of ellipticity of the nuclei showed strong correlation with granuloma size in untreated leprosy patients. This suggests that local pressure effects may influence epithelioid cell and macrophage nuclear morphology in leprosy lesions. PMID- 1409102 TI - Age-related modification of average volume and anisotropy of vascular smooth muscle cells. AB - The aim of this study was to determine what changes in the arterial wall are related to age. In two groups of rabbits, one young and one adult, the aorta and carotid were studied using a morphometric approach based on stereological axioms and planimetric morphometry. The problem of anisotropy of smooth muscle cells is discussed in detail. Two forms of anisotropy must be distinguished, that of single cell and that due to the histological pattern of the smooth muscle cells in the arterial wall. Our results show in adult animals, as compared to the young ones, statistically significant decrease in anisotropy of the cell pattern which tends to become more regular. Moreover, in aorta and carotid of young and adult animals there is an increment of 95.39% and 80% of the absolute cell volume, respectively. We suggest that there may be a direct relationship between aging and phenotypical modulation of the smooth muscle cells and that the modification of the architectural cell pattern with age may represent an adaptive event related to the change in forces acting upon the arterial wall. PMID- 1409103 TI - Age-dependent increase of rabbit aortic atherosclerosis. A morphometric approach. AB - Aging has been indicated as one of the major risk factors for development of atherosclerotic lesions, although the role aging plays, lacks accurate evaluation. Our study was aimed at quantitatively defining such a role by using morphometric analysis. Aged (median age 3 years and 8 months) and young (4 months) white New Zealand rabbits received a hyperlipemic diet enriched with a low dose of cholesterol for 16 months. At regular intervals, levels of serum lipemic parameters were checked. A Quantimet 920 image analyzer was used on paraffin-embedded sections of the entire aortas to measure the volume density of the tunica intima, the volume density of atheroma, the ratio intima/media and the surface area of the tunica intima. Our results indicated for aged hyperlipemic rabbits a statistically significant increase in all morphometric parameters examined as compared to young hyperlipemic animals, and no statistically significant differences in serum cholesterol, triglycerides and phospholipids. PMID- 1409104 TI - Morphological, immunohistochemical, stereological and nuclear shape characteristics of proliferative Leydig cell alterations in rats. AB - Proliferative Leydig cell (LC) alterations (hyperplasia, adenoma) of laboratory rats often pose diagnostic problems because the progression from normal to hyperplasia to neoplasia is continuous. The LC compartments of 130 Wistar rats (kfm: WIST strain) of approximately 2 years of age were examined. Ten typical cases conventionally classified as being normal or as showing diffuse or focal hyperplasia or small or large adenomata were investigated in more detail. In large adenomata, areas with large and small LC nuclei were identified. Immunohistochemical characterization, EM examination, as well as stereologic and planimetric investigations were performed. Hyperplastic and neoplastic LC essentially retained their normal appearance and immunohistochemical characteristics, but were found to contain more lipid droplets, fibroblast-like cells and patches of collagen than normal LC at the EM level. LC proliferation was accompanied by significant LC hypertrophy. LC nuclei of hyperplastic LC compartments were slightly larger while those of LC adenoma were markedly larger than nuclei of normal LC. The values for circle-related and ellipticity factors indicated that the nuclei of normal and hyperplastic LC were more markedly oval than nuclei of neoplastic LC. Concavity factor and bending energy measurements revealed that the small and oval nuclei of normal and hyperplastic LC had significantly more and deeper indentations than the larger and somewhat rounder nuclei of neoplastic LC. It is concluded that LC proliferations conventionally diagnosed as hyperplasia or adenoma on the basis of their size were composed of cytologically different LC populations. PMID- 1409105 TI - Changes in rat epiphyseal cartilage after treatment with dexamethasone and glycosaminoglycan-peptide complex. AB - In 3-month-old rats, systemic administration of glucocorticosteroids induced regressive changes in the epiphyseal plate cartilage. Dexamethasone treatment resulted in inhibition of both chondrocyte proliferation and cartilage matrix production. The inhibition of chondrocyte proliferation was determined histologically from the thickness of the epiphyseal plate, the number of cell columns and the ratio of proliferating to hypertrophied chondrocytes. The decrease in cartilage matrix production was measured autoradiographically by incorporation of radioactive 35S-sulphate. Concomitant treatment with glycosaminoglycan-peptide complex (GP-C = RUMALON) overcame the negative effect of dexamethasone. The values in the dexamethasone + GP-C group approached those of the control group and differed significantly from the group given dexamethasone alone. PMID- 1409106 TI - Morphometry of parenchymal and vascular alterations in ARDS after extracorporal carbon dioxide removal therapy (ECCO2-R-therapy). AB - The lungs of 12 patients suffering from ARDS treated by ECCO2-R-therapy were examined. The thickness of the interlobular septa, area portions of honeycombing, bleeding and lung parenchyma with diffuse alveolar damage were assessed by semi automatic image analysis. Medial thickness of the pulmonary arteries with an external radius ranging between 40 microns and 150 microns was assessed planimetrically. The area portion of honeycombing ranged from 0% to 66% (average: 28.8%, standard deviation: 17.0%). The thickness of interlobular septa was increased with values between 74.0 microns and 195.5 microns (average: 140.4 microns, standard deviation: 41.7 microns; normal controls: 72.0 microns +/- 19.5 microns). Parenchymal and vascular changes were closely related: Average medial thickness rose from nearly normal values (4.9%) in cases with low area portions of honeycombing and bleeding to the double (11.1%) of normal values in cases with area portions of honeycombing and bleeding greater than 40%. We conclude that parenchymal changes due to shock and high inspiratory O2 concentration lead to changes of the pulmonary arterial hemodynamics which result in a quickly developing medial hypertrophy. PMID- 1409107 TI - Metastatic capacity and differentiation in murine melanoma cell lines. A morphometric study. AB - A morphometric analysis was carried out on electron micrographs of cells of the F1 (low metastatic capacity) and F10 (high metastatic capacity) variant sublines of the murine B16 melanoma, both in in-vitro cultures and in lung-metastatic nodules developed after the intravenous injection of neoplastic cells in syngeneic C57 black male mice. A group of 28 morphometric parameters was derived to describe quantitatively each neoplastic cell profile. No qualitative difference was observed between the two cell lines. The quantitative expression of subcellular organelles was dissimilar in the two sublines, being consistently characterized, both in in-vitro cultured cells and in lung-metastatic colonies, by a significant decrease in the mean values of parameters related to melanosomes in the high metastatic capacity cell line (B16-F10). Moreover, in in-vitro cultured cells, indices describing heterochromatin masses and cytoplasmic membranous compartments displayed statistically significant differences between the two sublines. In this experimental system, an inverse relationship between metastatic capacity and differentiation is detected, since cells with a more aggressive metastatic behavior exhibit a decreased degree of differentiation. PMID- 1409108 TI - In situ analysis of adenohypophysis proliferative activity in beagle dogs. Preliminary results. AB - In order to establish control data on adenohypophysis cell cycle in beagle dogs, two different approaches were used. In the first approach, the adenohypophysis mitotic index (percentage of cells in mitosis: MI) was determined using pituitary glands from 50 control beagle dogs, 10 to 25 months old, from retrospective regulatory safety assessment studies. We found that the MI in males was 0.024 +/- 0.007% and in females 0.068 +/- 0.019%. The second approach involved the determination of the adenohypophysis cell fraction in S phase by means of bromodeoxyuridine (BrdU) anti-BrdU method in 16 control beagle dogs, 8 to 20 months old, from ongoing safety assessment studies. We found that the BrdU labeling index (percentage of BrdU-positive cells per total number of cells: BrdU LI) was 0.053 +/- 0.009% in males and 0.059 +/- 0.015% in females. Analysis of our data indicated that the results obtained from the BrdU LI were more reliable (coefficient of variation [CV] less than 0.07) compared to those obtained from the MI (CV greater than 1.4). No clear difference was found between male and female beagle dogs, regarding adenohypophysis cell proliferation. In both studies, adenohypophysis cell proliferation was found to be age-dependent, with the highest value in immature dogs. No correlation between estrus cycle in females and adenohypophysis cell proliferation was noted. PMID- 1409109 TI - Morphometric analysis on myocardial injury related to the use of high volume potassium cardioplegic solution during ischemic arrest. AB - We correlated the effects of high volumes of K+ cardioplegic solution on myocardial structure and function in 16 dogs following open-heart surgery. Eight animals received high volume potassium cardioplegic solution (25 cc/kg body weight, every 30 min) during 90 min of ischemic arrest (HVK-C group). The others received sufficient cardioplegic solution to maintain complete electrical arrest as defined by voltage monitoring criteria (VM group). Cardiac index (CI), left ventricular stroke work index (LVSWI), and myocardial contractility (dp/dt) were determined before arrest and after 90 min of ischemia and 45 min of reperfusion. Biopsies were taken for EM ultrastructure and ATP estimation. Morphometric analysis of EM micrographs found increased volume of damaged mitochondria (DMR) (p less than 0.025), damaged myofibrils (DMF) (p less than 0.001), intermyofibrilar edema (p less than 0.005), T-tubule and sarcoplasmic reticulum (p less than 0.05) in the HVK-C group. Left ventricular (LV) function was more depressed in animals receiving HVK-C. CI decreased by 1.8 +/- 0.4 l/min/square meter (p less than 0.01), LVSWS fell by 3.3 +/- 0.8 gm-m/beat/Kg (p less than 0.01), dp/dt decreased by 684 +/- 135 (p less than 0.0025). ATP decreased by 26% in HVK-C and by 12% in VM group (0.1 less than p less than 0.05). Structural damage (scores of injured volume of mitochondria and myofibrils) correlated with post-ischemic depression of LV function (Cardiac output and myocardial contractility), r = -0.72 and -0.66 (p less than 0.001 and 0.004). PMID- 1409110 TI - Comparison of the ECL-cell frequency in the stomachs of 3 different rat strains. AB - Three different rat strains, Sprague-Dawley, Wistar and Fischer 344, were treated for 3 months with 2 doses (0.8; 4 mg/kg) of the gastric acid suppressing ATPase inhibitor pantoprazole. The gastrin levels were determined, the height of the mucosa measured and the number of enterochromaffin-like (ECL) cells counted. Because these cells were stained according to the method of Grimelius they were designated as GPC (Grimelius positive cells). Under 4 mg/kg, the gastrin levels were increased 8 hours after administration, but fell again after 24 h. The Fischer rats showed the highest value. Also the height of the mucosa was increased under 4 mg/kg. A trend towards an increased mucosal height was noticeable even at 0.8 mg/kg. The number of GPC was determined in 2 ways: 1) without taking the mucosal height into account, 2) taking the height into account. An increase in GPC was observed at 4 mg/kg with both methods. PMID- 1409111 TI - Stimulation of bone marrow by administration of excessive doses of recombinant human erythropoietin. AB - Recombinant human erythropoietin (rhEPO) was administered intravenously to Beagle dogs in daily doses of 100, 500 and 3000 units/kg/day for 3 months. The high dose was more than 200-fold the therapeutic human maintenance dose. Such excessive rhEPO doses elicited extreme erythropoiesis. There was a dose-dependent stimulation of bone marrow fibroblasts, leading to bone marrow fibrosis in some of the high dose animals. The extent of myelofibrosis was intra- and interindividually different in various bones. Sternebrae proved to be practical for morphometric studies. The point-counting method was used for measurement. The portion of fatty tissue, sinusoids and fibrous tissue in the medullary space as well as the number of blood vessels and megakaryocytes were calculated. Such experimental conditions are not of relevance in human patients whose rhEPO therapy is interrupted as soon as their PCV reaches 35 vol%. Experimentally induced myelofibrosis should therefore not be considered as a risk in patients receiving therapeutic doses of rhEPO. PMID- 1409112 TI - Fractal dimension of pericellular membranes in human lymphocytes and lymphoblastic leukemia cells. AB - When blood cells are projected into an image plane their contours appear as borderlines of irregular shape with the property of the statistical self similarity. The dimension D of these cell perimeters may be fractal rather than an integer as in the Euclidean space. The fractal dimension D for different q'order moments was evaluated by means of a probabilistic method after recording EM image profiles of normal peripheral blood mononuclear cells (PBMN) and mature lymphocytes and also of lymphoblasts isolated from humans with acute leukemia or obtained by lectin stimulation in vitro. PBMN cells, CD 4 and CD 8 T-lymphocytes showed a fractal dimension D quite similar among five moments, ranging from 1.23 1.17. Cells of hairy-cell leukemia with highly convoluted morphology displayed D comprised between 1.32-1.36, whereas blasts of T or B acute lymphoblastic leukemia were characterized by a smaller D of 1.11 and 1.13-1.16 respectively. When normal T-lymphocytes were transformed into blasts by lectin PHA stimulation in vitro, the fractal dimension D was significantly reduced and found close to the value recorded on pericellular contour of blasts from acute T-lymphoblastic leukemia. PMID- 1409113 TI - Interaction of adenosine analogs with morphine in analgesic tests. AB - The effect of selective adenosine receptor agonists on nociceptive responses of mice and rats and on morphine analgesia was investigated. All compounds used: phenylisopropyladenosine (R-PIA), adenosine ethylcarboxamide (NECA), cyclohexyladenosine (CHA) and 2-chloroadenosine (2-CADO) exhibited antinociceptive action in mice and rats in the hot-plate (56 degrees C) and tail immersion (52 degrees C) tests. R-PIA, CHA and NECA potentiated the antinociceptive action of morphine in mice, and R-PIA and NECA--in rats. 2-CADO did not affect the morphine action in the tests. PMID- 1409114 TI - Pharmacokinetics of inulin in blood and central lymph in the rat. AB - Inulin was used as a model drug for the study of factors influencing the transport of drugs across the blood-lymph barrier. The model drug was administered iv (0.75, 7.5 and 37.5 mg/kg) as a bolus and by infusion. Kinetic parameters in blood and central lymph including lymphatic bioavailability (FL) were determined. It has been found that FL is influenced (increased) by larger doses of inulin (FL extent 0.934 +/- 0.250 - 1.914 +/- 0.250), infusion concentration ratio lymph/blood in steady state was 0.941 +/- 0.013. Identical kinetic parameters were found in rats with differentiated content of total lipids in lymph (in fed and fasted group, FL were 0.861 +/- 0.167 and 0.934 +/- 0.250 respectively). PMID- 1409115 TI - Stimulatory effect of low doses of mechlorethamine on humoral response of ovalbumin-immunized rabbits--comparison with levamisole. AB - The effect of low doses of mechlorethamine (1-10 micrograms/kg) and levamisole (2.5 mg/kg) on humoral response of rabbits immunized twice with ovalbumin (0.1 mg/kg) was compared. It was shown that mechlorethamine given in a dose of 5 or 10 micrograms/kg potentiates the increase in the level of serum anti-ovalbumin hemagglutinins; this increase is induced both after the first and the second (after 14 days) antigen administration. Levamisole acted similarly but with much lower efficiency. PMID- 1409116 TI - High-performance liquid chromatographic method for the simultaneous determination of propafenone and 5-hydroxypropafenone in human serum. AB - A simple, rapid and sensitive high-performance liquid chromatographic method for the simultaneous determination of propafenone and 5-hydroxypropafenone in human serum is described. Method involves a single-step extraction of the drug and its metabolite with dichloromethane:2-propanol (4:1 v/v) mixture from 0.2 ml of serum. Separation of the investigated compounds on deactivated Supelcosil LC18-DB column is accomplished by ultraviolet detection at 210 nm. The limit of detection is 10 ng/ml for propafenone and 4 ng/ml for 5-hydroxypropafenone. The method is useful for the routine monitoring of propafenone and its main metabolite in serum as well as for the pharmacokinetic studies. PMID- 1409117 TI - Vascular action of natural vasopressin-like peptides in isolated rat tail artery. AB - The literature data regarding the vasoconstriction potency of natural vasopressin like peptides are contradictory. The cumulative concentration-response curve for arginine-vasopressin (AVP), lysine-vasopressin (LVP), arginine-vasotocin (AVT), lysine-vasotocin (LVT) and phenypressin (PHP) on the isolated rat tail artery was determined. The potency rank of these peptides on the vascular smooth muscle of the rat tail artery was the following: AVP greater than LVP greater than AVT = LVT greater than PHP. The results are discussed in comparison to the data in the literature. PMID- 1409118 TI - Synthesis and some pharmacological properties of new V1/V2 antagonists of arginine-vasopressin with structural changes at their N-terminals. AB - In an effort to develop more effective and selective V2-antagonists of arginine vasopressin (AVP) we designed and synthesized four new analogs of this hormone. The peptides were designed in order to explore how the combination of modification of thioacids occupying position 1 and substitutions of positions 2 and 4 by D-Phe and Ile respectively, will influence their antagonistic properties. Three of the reported analogs are moderately potent V1/V2 antagonists. PMID- 1409119 TI - Synthesis and some pharmacological properties of 1,2-amino ethers with natural monoterpene structures. AB - Synthesis and physicochemical and pharmacological properties of 10 analogs of 2 [2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)ethoxy]N, N-diethylamino ethane (3) have been described. The compounds possess toxicity close to or lower than the parent compound--myrtecaine, have no antiarrhythmic activity but some of them (15, 16, 22, 24), similarly as compound 3, show quite strong local anesthetic action. PMID- 1409120 TI - Interaction of epidermal growth factor and transforming growth factor beta in human prostatic epithelial cells in culture. AB - The present study was conducted to study the interaction between epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta) in benign human prostatic epithelial cells in culture. Primary cultures of human prostatic epithelial cells were grown in complete WAJC, which consisted of WAJC-404 medium and, in addition to other defined additives, EGF and bovine pituitary extract (BPE). Incomplete WAJC contained the same composition except EGF and BPE were deleted. TGF-beta was added into media at concentrations of 0, 0.1, and 1.0 ng/ml. When cells were grown in complete WAJC, they proliferated rapidly. Cell proliferation was greatly suppressed when incomplete WAJC was used. Addition of TGF-beta to these cultures caused a significant reduction in the final cell number when either complete WAJC or incomplete WAJC was used. In additional experiments, cells were prelabeled with 3H-thymidine for 72 hr prior to treatment with TGF-beta. The percentage of radioactivity released into the medium at the end of a 6-day culture was used as an indication of the extent of cell death. Trypan blue exclusion test was also used to assess the extent of cell death. Addition of TGF-beta into complete WAJC did not significantly affect the extent of cell death beyond what was considered as the result of normal cellular turnover. Addition of TGF-beta into incomplete WAJC, however, caused a significant increase in the percent of cell death in the culture. These results demonstrated an interaction between EGF and TGF-beta in proliferation and cell death in human prostatic epithelia in culture. In the presence of EGF alone in the culture medium, prostatic epithelial cells were stimulated to proliferate. The rate of proliferation was greatly diminished when EGF was deleted from the medium or when TGF-beta was added in the presence of EGF. Finally, cell death was induced when TGF-beta was added into the medium in the absence of EGF. PMID- 1409121 TI - Correlation between the prostatic vein and vertebral venous system under various conditions. AB - In dogs, the venous blood from the prostate gland was observed under X-ray fluoroscopy to drain into the vertebral venous system under conditions of abdominal compression, the addition of various intraabdominal pressures, and occlusion of the inferior vena cava by a balloon catheter. Pressure in the inferior vena cava and abdominal cavity were measured simultaneously. The venous blood draining from the prostate gland started to flow from the inferior vena cava into the vertebral veins at more than 25 mmHg of intraabdominal pressure with the animal in the supine position. The average pressure of the inferior vena cava draining into the vertebral veins was 12.8 +/- 1.3 mmHg in the supine position and 21.1 +/- 2.7 mmHg in the standing position. The average intraabdominal pressures were 35.5 +/- 3.9 mmHg and 30.1 +/- 2.8 mmHg, respectively. Under conditions of abdominal compression and balloon occlusion of the inferior vena cava, the materials flowed into the vertebral venous system from various routes, such as the internal iliac vein, common iliac vein, and inferior vena cava. It was suggested that the inferior vena caval blood easily enters the vertebral venous system in the standing position by adding high intraabdominal pressure, and that the vertebral venous system may be useful for experimental study of drug administration in bone metastasis of prostate cancer. PMID- 1409124 TI - Allograft bones and soft tissues: the benefits of clinical research. PMID- 1409123 TI - Health care financing: the real issues. PMID- 1409122 TI - Presence of calcitonin-like immunoreactivity (iCT) in human prostate gland: evidence for iCT secretion by cultured prostate cells. AB - Immunoreactive calcitonin (iCT) has been detected in human prostate tissue extracts as well as seminal plasma. The present studies were undertaken to examine whether iSCT (immunoreactive salmon CT-like human peptide) co-exists with iHCT (thyroid CT-like substance) in human prostate tissue extracts, and whether these substances are secreted by primary prostate cells in culture. Since the local secretion of these substances seems to increase in some neoplasms, a second objective of the study was to examine whether basal secretion of iCTs from primary prostate cells is increased in carcinoma. The present results have shown that both iHCT and iSCT were present in prostate tissue extracts. The mean iHCT levels in extracts of benign hyperplastic prostates (BPH) were 0.59 ng/g prostate, and these were significantly lower than iHCT concentrations in prostatic carcinoma (PC) (2.53 ng/g). No significant differences in their iSCT contents were observed. However, the results from culture of over 90 individual prostate tissue specimens from BPH or PC indicate that primary prostate cells secreted detectable quantities of iSCT and the basal release of this material from PC prostate cultures was almost four-fold higher than that from BPH prostate cultures. These results suggest that a CT-like immunoreactive material is secreted by primary prostate cells in culture, and the basal secretion of this material is significantly higher in PC cells as compared to BPH cells. Endogenous secretion of prostatic CT, and the elevation of its expression in PC suggest that it may serve as a regulatory factor in the pathophysiology of the prostate gland. PMID- 1409125 TI - Current status of allografting for bone tumors. AB - Over the past 20 years the Orthopaedic Oncology Unit of the Massachusetts General Hospital has performed over 660 massive cadaveric allograft transplantations, mostly for patients with bone tumors. The overall success rate for such procedures is around 80%, with most of the failures occurring in the first 3 years as a result of fracture (19%), nonunion (14%), and infection (10%). With longer follow up, late occurring osteoarthritis has been noted in approximately 17% of those patients at risk, suggesting that the articular surface begins to "wear" at 5 years. Some problems remain with the procedure, and more study of such aspects as the immune mechanism, cryopreservation of cartilage, maintaining the status and safety of the bone banking system, and improving the techniques of surgery ultimately may lead to a more uniform and predictable success rate. PMID- 1409126 TI - Current procedures for banking allograft human bone. AB - The demand for bone and soft tissues for surgical usage has increased rapidly as the efficacy and safety of these materials has been demonstrated. Advances in technology and procedures used to prepare the tissues have also grown in sophistication and remain a dynamic area. How tissue banks screen donors and prepare allografts impacts on the risks and benefits of these materials. Surgeons should understand how tissue banks supplying their graft materials work and have confidence in this treatment option. They will then be prepared to educate their patients to help them make informed decisions concerning allograft usage. PMID- 1409127 TI - Immune responses to osteochondral allografts: nature and significance. AB - Osteochondral allografts evoke immune responses. The nature of these immune responses and their biologic significance are still only partially understood. It is clear, however, that cell surface antigens of the major histocompatibility complex represented on the cellular elements of bone grafts cause T-cell activation, specifically those of the suppressor/cytotoxic phenotype. In numerous animal models, the most immunogenic bone allografts (mismatched, fresh) have demonstrated the poorest clinical and biologic outcomes, while more closely matched and/or grafts treated to reduce immunogenicity (frozen, freeze-dried) have more successfully incorporated. These observations support the hypothesis that immune responses against bone-graft related antigens have biologic significance and that reducing these responses may improve clinical results. PMID- 1409128 TI - Fresh and frozen articular cartilage allografts. AB - Fresh and frozen cartilage allografts both function well to relieve joint pain due to cartilage injury. Fresh cartilage allografts appear to remain alive for many months and are most applicable to small injuries such as osteochondritis dissecans, traumatic defects, and osteonecrosis. Frozen cartilage allografts have been used mostly for treatment of bone tumors which most often involve the subchondral and the metaphyseal areas of the long bones, particularly around the knee and hip. Frozen cartilage allografts appear to survive well and maintain joint space for several years. Deterioration of either type of graft does not appear to result in joint pain, making these grafts useful for long periods of time. PMID- 1409130 TI - Use of allografts and prostheses in the reconstruction of failed total hip replacements. PMID- 1409129 TI - The long-term success of fresh, small fragment osteochondral allografts used for intraarticular post-traumatic defects in the knee joint. AB - Ninety-two fresh osteochondral allografts were implanted in 91 patients with posttraumatic osteoarticular defects of the knee joint. These patients have been prospectively followed since 1972. An analysis of long-term survival of these grafts has been performed to determine their success rates: 75% at 5 years, 64% at 10 years, and 63% at 14 years. An evaluation was made between unipolar grafts, which involve only one surface of the compartment, and bipolar grafts, which involve both surfaces. The unipolar grafts had a lower failure rate at all time periods compared to bipolar grafts, with 76% survival at 5 years, 69% at 10 years, and 67% at 14 years. While investigating other factors that might affect the survival of the fresh osteochondral allografts, we calculated the influence of the anatomical location of the graft, patient sex, and patient age. There was no meaningful impact on allograft survival by either the location of the allograft or the sex of the patient. However, there was a significant effect on allograft longevity in terms of patient age, with patients under age 60 doing better. The best indication for the use of unipolar fresh osteochondral allografts is for posttraumatic defects in relatively young, active patients. Joint malalignment should be corrected to achieve best results. PMID- 1409131 TI - Clinical use of fresh, frozen soft tissue allografts. AB - Fresh frozen allograft tissue provides a good alternative to autogenous tissue for the treatment of patients with symptomatic ligamentous deficiency. While transmission of AIDS and other infectious diseases remains a small possibility, allografts provide the advantages of shorter operative time, small incisions, no damage to a patient's own tissues, and superior usefulness in multiple reconstructions, as well as revision of failed autogenous reconstructions. An independent, critical evaluation of the 4-year results of patients with allograft ACL reconstructions is presented. Issues important in allograft tissue recovery, banking, and intraoperative preparation are reviewed. PMID- 1409132 TI - Autogenous bone grafts: nonvascular and vascular. AB - Nonvascularized autogenous bone grafts have been used for at least 150 years. Vascularized bone grafts were first done only 17 years ago. We now know that bone grafts act through osteoconductive and osteoinductive mechanisms to produce new bone. Autogenous bone grafts remain the gold standard against which allografts and artificial graft materials should be measured. PMID- 1409133 TI - The Clinton and Bush health care proposals: will either plan become reality? PMID- 1409134 TI - Pathogenesis and clinical significance of hemophagocytic syndrome: hypothesis. PMID- 1409135 TI - Immunofluorescence studies of lung tissue in cystic fibrosis. AB - Previous studies have suggested that immune mechanisms contribute to lung injury in cystic fibrosis (CF); however, there have been no comprehensive studies of immunofluorescent staining patterns in CF lung tissue. We performed immunofluorescence (IF) studies for immunoglobulins, C3, and fibrinogen on autopsy frozen lung tissue from 21 CF patients. Results were compared with lung findings in patients without CF. In CF-derived lung tissue fibrinogen was ubiquitous along the alveolar wall, alveolar space, and interstitium. Free immunoglobulin G (IgG) and IgA coated the alveolar surface segmentally in 14 and 6 cases, respectively. Unequivocal interstitial deposits were infrequent and IgM was present in blood vessels in one patient only. Intra-alveolar and interstitial inflammatory cells demonstrated cytoplasmic IgG, IgA, and IgM, respectively, in 18, 14, and 6 patients. C3 was seen only segmentally along the alveolar wall in two patients and in blood vessels in one. Antinuclear antibody (ANA) staining of interstitial cells for C3 and immunoglobulins was seen in five patients, four of whom had interstitial pneumonitis. Insignificant amounts of alveolar or interstitial fibrinogen and immunoglobulins in inflammatory cells were seen in controls in the absence of lung inflammation. The IF patterns were similar in the inflammatory lesions of CF and control specimens. The IF patterns observed in CF lung tissue are consistent with nonspecific vascular leakage and chronic inflammation with little evidence of immune complex deposition in the interstitium or blood vessels. This study confirms previous reports of ANA activity in CF patients, although the significance of this finding is unknown. PMID- 1409136 TI - Fatty change of the pediatric myocardium. AB - The myocardium was studied for the presence of fat in 980 pediatric deaths over a wide age range during a 10-year period. Of these, only 67 cases (7%) were found to have fatty change. The cause of death varied widely and no common pathogenetic factor was identified. Infections and congenital disorders constituted the most frequent causes of death associated with fatty change. The degree of fatty change was variable. Severe fatty change correlated with severe panacinar fatty change of the liver. The pathogenesis of the lesion is discussed. PMID- 1409137 TI - Tracheal cartilaginous sleeve. AB - Tracheal cartilaginous sleeve (TCS) is a rare congenital malformation in which discrete cartilaginous rings are replaced by a grossly uninterrupted cartilaginous sleeve. Seven previous patients with TCS have been reported in the world literature; in each instance, TCS was associated with craniosynostosis (CS). We report details of five additional patients with TCS, of whom four had a dominantly inherited CS. Gross examination of the available tracheas and bronchi demonstrates a cartilaginous sleeve with posterior interruption but lacking a normal pars membranacea. The stained and cleared tracheas all demonstrate variable ring formation, usually limited to the posterolateral aspect. The functional significance of TCS, if any, is unknown. No data are available on the prevalence of TCS in CS syndromes. The formation of TCS implies a common mesenchymal defect in which normally discrete structures fuse and is probably analogous to other mesenchymal abnormalities seen in these patients. PMID- 1409138 TI - Coexisting endogenous lipoid pneumonia, cholesterol granulomas, and pulmonary alveolar proteinosis in a pediatric population: a clinical, radiographic, and pathologic correlation. AB - Benign pulmonary diseases that have been associated with the accumulation of endogenous lipids within the alveoli, bronchioles, and interstitial tissues include endogenous lipoid pneumonia (ELP), pulmonary alveolar proteinosis (PAP), pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG), various xanthomatous lesions, and malakoplakia. In ELP, fat-filled finely vacuolated macrophages fill the alveoli. In PAP, the aveoli become filled with cholesterol and periodic acid-Schiff (PAS)-positive acellular debris. In PICG, cholesterol esters are released from degenerating macrophages and, as organization occurs, the cholesterol is deposited in the form of acicular clefts within the interstitium. These morphologically distinct presentations of endogenous lipid deposition within the lung have long been thought to represent unique disease processes but several authors now postulate a possible relationship between these entities. We report here on the clinical, radiographic, and morphologic findings in eight pediatric patients with diverse primary disease processes who were subsequently found to have varying and often coexisting degrees of ELP, PAP, and PICG. PMID- 1409139 TI - Microdissection study of the myenteric plexus in acardia, ataxia-telangiectasia, cystic fibrosis, extrahepatic biliary atresia, pediatric AIDS and Werdnig Hoffmann disease. AB - Microdissection-point count morphometric study of the myenteric (Auerbach) plexus or esophagus, small intestine, and colon was done for infants and children with acardia (2), ataxia-telangiectasia (5), cystic fibrosis of the pancreas (CFP) (25), extrahepatic biliary atresia (EBA) (17), pediatric AIDS (10), and Werdnig Hoffmann disease (WHD) (8). Values for fractional area of neural tissue in the plane of the plexus were compared to those of control patients in same age range as those in each disease category by t-test. Statistically abnormal values included low values for small intestine and colon in Werdnig-Hoffmann disease, high values for small intestine and colon in biliary atresia, and high value for colon but a low value for small intestine in cystic fibrosis. Values for all three loci were within the normal range for ataxia telangiectasia and pediatric AIDS. The mechanisms of the low value for small and large intestines in WHD, which causes chronic constipation as a result of skeletal muscle weakness, and of the high values for colon in CFP and EBA, both causing malabsorption with bulky stools, are unclear. The value for small intestine in acardia was normal for term but lower than expected for fetal bowel of the same size, possibly because of reduced neural crest inflow to the fetal bowel. PMID- 1409140 TI - Transthoracic herniation of the fetal lung: bagpipe lung. AB - We describe a case of subtotal herniation of a lung through an intercostal space into an extrathoracic (axillary) position that occurred in a 16-week-old fetus. There was no malformation of the thoracic wall other than the hiatus at the site of herniation. The left and the right lungs were of similar size and weights and the lung/body weight ratio was normal. Histology revealed no difference between the normal and the abnormally positioned lung. We were unable to find a report of a similar case of the condition, which has implications for concepts of lung development. PMID- 1409141 TI - Osteogenesis imperfecta and Ebstein's anomaly: a case report with autopsy findings. AB - Osteogenesis imperfecta is an inherited disorder of collagen synthesis. It has a wide range of phenotypic expressions, but cardiovascular anomalies tend to be rare. When they do occur, they usually consist of aortic or mitral valve disease. We report an autopsy case of a 36-week gestation infant with coexisting osteogenesis imperfecta and Ebstein's anomaly. The simultaneous occurrence of two relatively rare entities may reflect a generalized expression of an underlying collagen synthesis defect. PMID- 1409142 TI - Pulmonary hypertension with coexisting portal hypertension. AB - A 10-year-old boy who had portal hypertension secondary to portal fibrosis/intrahepatic biliary atresia developed syncopal episodes related to strenuous activity. A work-up excluded a metabolic or neurologic etiology and cardiac catheterization demonstrated significant pulmonary hypertension. Six months later he died and an autopsy revealed pulmonary plexogenic arteriopathy without microemboli. Previous reported cases of this symptom complex are reviewed. In addition, he had a history of nonspecific colitis, ulcerative stomatitis, and conjunctivitis responsive to steroid therapy. The possible relationship of these manifestations to the portal pulmonary pathology is discussed. PMID- 1409143 TI - Fetal rhabdomyoma and nevoid basal cell carcinoma syndrome. AB - A 6-year-old white female presented with a fetal rhabdomyoma of the posterior mediastinum and retroperitoneum. Radiologic evaluation and family history revealed features of the nevoid basal cell carcinoma syndrome (NBS). Literature review disclosed two other children with NBS and fetal rhabdomyoma, which should be regarded as one of the soft tissue tumors associated with NBS. PMID- 1409144 TI - Fetal distribution of cocaine: case analysis. AB - The implications of gestational cocaine use are widely documented. There is evidence that cocaine crosses the placenta in animals and humans; however, the fetal distribution of the drug and its metabolites has not been documented. We describe the distribution of cocaine and benzoylecgonine (BE) in the fetus of a cocaine user mother. Cocaine and BE were detected in brain, scalp, liver, kidney, heart, placenta, blood, and hair. The liver contained substantially more cocaine than other tissues, whereas the brain had more BE than any other sample. PMID- 1409145 TI - Brain stem and cervical cord dysraphic lesions in iniencephaly. AB - Iniencephaly is a rare, lethal, axial dysraphic malformation complex diagnosed on the basis of three cardinal features: deficiency of the occipital bone, cervicothoracic spinal retroflexion, and rachischisis. The majority of the patients also have various associated viscerae malformations. An iniencephalic female fetus delivered at 35 5/7 weeks of gestation revealed severe anomalies of the central nervous system and the spine: the cerebellar vermis was hypoplastic, the medulla oblongata was flattened and broadened, and the cervical canal was widely patent dorsally. The thoracolumbar spinal cord had a duplicated central canal and lacked a dorsal fissure, representing a minor degree of diastematomyelia. The cervicothoracic spine showed severe bony anomalies including aplasia and fusion of vertebral bodies. PMID- 1409146 TI - High incidence of pulmonary foreign body embolism. PMID- 1409147 TI - Reproducibility of Naeye's seven tissue markers of hypoxia. PMID- 1409148 TI - Angiosarcoma of the liver in childhood: a clinicopathologic and follow-up study of 10 cases. AB - The clinical, morphologic, and follow-up findings in 10 cases of childhood hepatic angiosarcoma are reported. Six patients were female and four were male. The age range was 18 months to 7 years, with a mean of 3.7 years. The usual presenting feature was an abdominal mass, with or without associated symptoms. The histologic pattern of childhood hepatic angiosarcoma typically consists of large hypercellular whorls of spindled sarcoma cells intermingled with bile ducts, vessels, and collagen. Factor VIII staining of tumor cells is focal, cytoplasmic, and weak in character. Intracellular eosinophilic, PAS-positive globules are present in most cases and may be abundant. The prognosis is poor; follow-up available in seven cases showed only one to be alive 32 months after diagnosis. The remaining six patients had died 0-27 months (mean 10 months) after diagnosis. PMID- 1409149 TI - Persistent pulmonary hypertension of the newborn due to alveolar capillary dysplasia. AB - Three unrelated female term infants died when less than 1 month old from intractable pulmonary hypertension associated with deficient capillaries in airspace walls, anomalous small pulmonary veins in bronchiolar-arterial rays, and medial thickening in small pulmonary arteries together with peripheral muscularization. This complex vascular abnormality in the lungs has been termed alveolar capillary dysplasia and/or misalignment of lung vessels in seven previously reported cases. Each infant also showed abnormally immature parenchymal development in the lungs, as was noted in four of the seven prior cases. One had phocomelia; four of the seven prior cases had a variety of congenital anomalies. The primary pulmonary vascular anomaly is likely to be a failure of fetal lung vascularization dating from the second trimester and to be due to action of an unknown teratogen. Centroacinar veins may represent bronchial veins that do not normally develop beyond the ends of cartilaginous bronchi. Pulmonary arterial occlusive changes are interpreted as reactive to obstruction at the level of pulmonary arterioles. PMID- 1409150 TI - Digestive tract involvement with exudative enteropathy in Langerhans cell histiocytosis. AB - Protein-losing enteropathy was observed in two children with Langerhans' cell histiocytosis (LCH). One patient was an infant with congenital cutaneous lesions; the second child had sigmoid and lymph node infiltration. Electron microscopy and immunohistochemistry confirmed, in both, infiltration of duodenum, skin, and liver by LCH. Gastrointestinal involvement by LCH seldom produces prominent clinical manifestations but indicates widespread multisystem disease. Immunohistochemical and/or ultrastructural features allow definitive diagnosis from mucosal biopsy specimens. Review of the literature of gastrointestinal infiltration by LCH emphasizes its poor prognosis, especially when associated with organ dysfunction. PMID- 1409151 TI - Mesenchymal hamartoma of the chest wall: a cooperative study with review of the literature. AB - The clinicopathologic features of three examples of mesenchymal hamartoma of the chest wall are described. The entity has been recorded under a number of names including osteochondroma, osteochondrosarcoma, benign chondroblastoma, mesenchymoma, and chondromatous hamartoma. The condition is manifest at birth or shortly thereafter with deformity of the chest wall and respiratory distress. Radiographic examination reveals a well-defined, partly calcified mass involving one or more ribs. The tumor is composed predominantly of chondroid tissue with large endothelium-lined blood spaces and immature mesenchyme with osteoclastic giant cells and osteoid. We review the literature and suggest that the lesion should be distinguished from aneurysmal bone cyst, chondroma, and other mesenchymal neoplasms. In order to avoid local recurrence the recommended treatment is complete surgical resection. PMID- 1409152 TI - X-linked myotubular myopathy: a case report of prenatal and perinatal aspects. AB - Nine families have been reported in which male newborns presented with X-linked myotubular (centronuclear) myopathy. Little is known about the biochemical basis of this disorder or about its natural history in utero. We report a family in which an infant with myotubular myopathy presented in utero with polyhydramnios, poor fetal movement, and fetal cardiac arrhythmias. Shortly after birth the infant died from severe respiratory insufficiency. Gas chromatography-mass spectrophotometry for serum organic acids showed a large octanoic acid peak, but total acyl-CoA dehydrogenase activities in liver were normal. The maternal family history was significant for two perinatal male deaths. Postmortem examination revealed generalized muscle wasting, cardiac enlargement, cryptorchidism, and flexion contractures. Examination of muscle showed numerous fibers that had enlarged, centrally located nuclei and perinuclear clear zones. The muscle fibers were hypotrophic and predominantly of type I. Biopsy specimens of the muscles of the mother and maternal aunt had increased numbers of centrally located nuclei. Neurologic examination was normal. The case demonstrates the typical clinical course, pathology, and family history of severe X-linked myotubular myopathy. In addition, it confirms the reported detection of fetal cardiac arrhythmias and documents what may be an abnormality in fatty acid oxidation. PMID- 1409153 TI - Fetal and placental pathology in two cases of maternal varicella infection. AB - We describe the fetal and placental pathology in two cases of maternal varicella infection. Varicella in pregnancy is uncommon, and although sporadic cases of fetal involvement are described very little regard has been paid to placental features. Only one previous report describes the changes in both the fetus and its associated placenta. In both our cases the placenta showed chronic villitis with with granuloma formation, and occasional cells with nuclear viral-like inclusions were detected. Cells with similar inclusions were found in the lung interstitium, and foci of dystrophic calcification were present in the liver. PMID- 1409154 TI - Inflammatory pseudotumor of the kidney with extensive metaplastic bone. AB - Inflammatory pseudotumor (IPT) of the kidney is a very rare lesion. We describe an 8-year-old boy with IPT of the kidney presenting as a single episode of hematuria. The case highlights a new feature, metaplastic bone, not previously described in IPT. This new feature may be helpful in establishing the correct preoperative and histopathologic diagnosis of IPT of kidney and avoiding inappropriately aggressive therapy. Despite its rarity, IPT of the kidney should be kept in mind in the differential diagnosis of a solitary renal mass. PMID- 1409155 TI - Hyperplasia of lymphoglandular complexes in colon segments in Hirschsprung's disease: a form of diversion colitis. AB - This is a study of the size and number of lymphoglandular complexes (LGDs) in the resected segment of aganglionic left colon of 20 children (mean age 26 months) obtained several months to years after being defunctionalized by proximal colostomy, compared with 5 controls (mean age 20 months). All the resected aganglionic segments had a nodular mucosa. The number of LGCs/mm of muscularis mucosae was 0.58 +/- 0.2; in controls the number was 0.24 +/- 0.12 (P less than .0025). The mean size of LGCs in aganglionic colon was 1.23 +/- 0.27 mm, and in controls it was 0.57 +/- 0.21 (P less than .0005). Because LGCs have been related to antigen processing, hyperplasia of LGCs in defunctionalized colonic segments of Hirschsprung's disease may represent a reaction to stagnant contents. Its combination with cryptitis (present in six cases) may represent a form of diversion colitis, a condition recognized in adults in bypassed colonic segments after surgical diversion of the fecal stream. PMID- 1409156 TI - Intestinal ganglioneuroblastoma in a 22-week fetus. AB - The clinical history and autopsy findings of a 22-week fetus with intestinal ganglioneuroblastoma, cardiac anomalies, omphalocele, and ileal atresia are presented. Ganglioneuroblastoma was confined to the large intestine and was not suspected prenatally despite ultrasonographic examination. Although enteric ganglia share neural crest lineage with other sites of congenital neuroblastoma, this is the first report of a primary intestinal ganglioneuroblastoma in a fetus or child. Various hypotheses are discussed to explain the coexistence of cardiac malformation and congenital neuroblastoma in this fetus and other cases in the literature. It is hypothesized that other malformations evident in this fetus were caused by the tumor, possibly as teratogenic effects of neuroblastoma derived catecholamines during embryogenesis. PMID- 1409157 TI - Studies of vertebral coronal cleft in rhizomelic chondrodysplasia punctata. AB - Dissection and serial section-reconstruction preparations from vertebrae with coronal cleft of a 2 5/12-year-old girl with rhizomelic chondrodysplasia punctata are described. The cartilage plate between the dorsal and ventral vertebral ossification centers, abnormal thickness of which is the explanation of the radiologic coronal cleft, shows differences in thickness, with dorsal and ventral midline extensions and with small foci of communication of the cancellous bone of the dorsal and ventral ossification centers of the vertebral body bilaterally. Although the process in coronal cleft is in some ways similar to that of radiologic "retarded epiphyseal closure," the explanation of the coronal clefts in rhizomelic chondrodysplasia punctata appears to be overproduction of cartilage in the zone between the dorsal and ventral vertebral body ossification centers, plus reduced removal of cartilage cells from this zone. No evidences of persistence of notochord cells were seen microscopically in sections of the coronal clefts. PMID- 1409158 TI - In situ choriocarcinoma arising in partial hydatidiform mole: implications for the risk of persistent trophoblastic disease. AB - The risk of persistent trophoblastic disease following partial hydatidiform mole is controversial. In spite of claims that 4 to 11% of cases require chemotherapy, there is a paucity of affected patients in the literature. A critical review of those patients suggests an alternative or unproven diagnosis in the majority. An instance of placental in situ choriocarcinoma arising in a partial mole is reported. Because in situ choriocarcinoma may represent the incipient lesion in the majority of the one-third of cases of gestational choriocarcinoma that follow a normal pregnancy, we postulate that the presence of the in situ lesion in a partial mole supports the view that the risk of persistent trophoblastic disease may be no greater after partial mole than after a normal gestation. PMID- 1409159 TI - Neurofibromatosis cerebral vasculopathy in an infant: clinical, neuroradiographic, and neuropathologic studies. AB - An infant with neurofibromatosis developed recurrent cerebrovascular accidents beginning at 3 months of life. Cerebral arteriography demonstrated large-vessel occlusive disease and bilateral severe moyamoya. At autopsy these lesions were apparent on gross examination, and advanced intimal and medial dysplasia was seen on microscopic examination of both the anterior and posterior circulations. Although rare, neurofibromatosis cerebrovasculopathy may occur in young infants and may account for some strokes in this age group. PMID- 1409160 TI - Postmortem identification of medium chain acyl-CoA dehydrogenase (MCAD) deficiency. PMID- 1409161 TI - Allergic rhinitis. PMID- 1409162 TI - Amphetamine and methamphetamine during the 1990s. PMID- 1409163 TI - Prenatal diagnosis. AB - The enormous progress witnessed in the field of prenatal diagnosis during the past two decades is likely to continue into the future. Improved imaging techniques are likely to enhance the resolution of noninvasively obtained fetal images considerably over their current excellent quality. Although this undoubtedly will be true for ultrasonography, the increased speed of magnetic resonance equipment may offer a new realm of imaging possibilities. Computerized image processing, analysis, and three-dimensional reconstructions all should make interpretation of fetal images easier and more understandable to the nonspecialist. Advances in molecular genetics will continue to accelerate, greatly expanding the range and accuracy of prenatal diagnosis. The alert pediatrician who is sensitive to genetic issues may, by early detection of pediatric disorders and careful family history assessment, be in a position to identify families at risk for serious genetic conditions and provide the opportunity to make informed decisions on reproductive options that avert a major tragedy. The pediatrician, working with obstetric colleagues, should be part of a team effort to support families going through prenatal testing. Familiarity with these rapidly changing technologies will make it far easier to support the family needing additional explanation about prenatal diagnosis issues. PMID- 1409164 TI - Childhood tuberculosis during the 1990s. PMID- 1409165 TI - Otitis media--the forest and the trees. PMID- 1409166 TI - Breast imaging. A practical look at its capabilities and its limitations. AB - The film-screen technique is evolving as the standard for mammography. Sonography is the only other method that currently has a defined role in breast imaging. Mammography should be performed at facilities that have received American College of Radiology accreditation or its equivalent, because technical quality assurance is an important part of mammographic practice. Interpretive quality may be assured by outcome audits performed by mammography facilities. Primary care physicians are best suited to encouraging eligible women to undergo screening studies and should consider these recommendations: Refer patients for screening mammography to accredited facilities according to established guidelines. Educate patients about the need for regular screening. Provide annual breast physical examination. Refresh your knowledge on breast health and the techniques of physical examination if necessary. Teach patients breast self-examination techniques. Demand low-cost, high-quality screening mammography; be aware of local variability of charges and quality. PMID- 1409167 TI - Legal issues in managing breast disease. AB - The impact of legal issues in breast cancer care reflects the significance of breast cancer as a health concern of women. Breast cancer has emerged as a leading liability risk for primary care physicians, with most cases focusing on delayed diagnosis. Although the clinical impact of delayed diagnosis of breast cancer is often controversial, physicians should strive to diagnose breast cancer as early as possible in the natural history of the disease. No currently available data suggest that a delay of less than 2 months between the onset of symptoms and diagnosis or treatment adversely influences outcome. Techniques that help physicians reduce the liability risks associated with breast cancer care include patient education, adequate documentation and follow-up, and referral or consultation in high-risk situations. PMID- 1409168 TI - Bush vs Clinton on artichokes, tomatoes, and healthcare. PMID- 1409169 TI - Asymptomatic HIV infection. A primary care disease. AB - Asymptomatic human immunodeficiency virus infection is a disease entering the primary care arena more and more frequently. Patients may be monitored in this setting until complications and clinical deterioration develop (typically after several years). As the disease progresses, referral to consultants who specialize in AIDS may be appropriate. However, many patients do not live near a major healthcare center and do not have the financial, physical, or emotional capability to travel to one as they become sicker. In these cases, primary care physicians, with the aid of a personally chosen network of specialized consultants, should offer care as the disease progresses to its terminal stage. PMID- 1409170 TI - Are your patients satisfied? Strategies that may help you avoid a formal complaint. PMID- 1409172 TI - Fever of unknown origin in the elderly. A sequential approach to diagnosis. AB - Elderly patients with persistent unexplained fever require a diagnostic evaluation that focuses on specific infections (eg, occult abdominal abscess, bacterial endocarditis, miliary tuberculosis), rheumatic disorders (eg, temporal arteritis, polyarteritis nodosa), and neoplasms (eg, lymphoma, nephroma). Assessment is directed by the subtle clues elicited from meticulous, repeated history taking and physical examination. Therapeutic trials or exploratory laparotomy may be appropriate but should not be attempted out of a sense of frustration. PMID- 1409171 TI - Acne vulgaris. Topical and systemic therapies. AB - Acne vulgaris is a condition commonly treated by primary care physicians. An understanding of the causes of the disease and methods of clinical evaluation allows selection of appropriate therapy. Effective treatment is available for all types of acne, including severe, nodulocystic forms. Regardless of the regimen chosen, patients should receive encouragement and instructions about the necessity of regular ongoing treatment for a successful outcome. PMID- 1409173 TI - Magnesium deficiency and diabetes mellitus. Causes and effects. AB - A large body of evidence demonstrates the prevalence and adverse clinical consequences of magnesium deficiency in patients with diabetes mellitus. It would be prudent for physicians who treat these patients to consider magnesium deficiency as a contributing factor in many diabetic complications and in exacerbation of the disease itself. Repletion of the deficiency or prophylactic supplementation with oral magnesium may help avoid or ameliorate such complications as arrhythmias, hypertension, and sudden cardiac death and may even improve the course of the diabetic condition. PMID- 1409174 TI - Stress and the heart. Mechanisms, measurement, and management. AB - Unrelieved physical or mental stress and repeated episodic stress are ultimately harmful to the cardiovascular system and thus can be life-threatening. In this article, Dr Eliot describes efforts to quantify the psychophysiologic responses to stress and to identify the components of stress and its clinical consequences. He also explains the importance of controlling the real-life episodic fluctuations in blood pressure that occur daily in response to stress. PMID- 1409175 TI - Coronary artery disease in surgical patients. Preoperative evaluation. AB - Primary care physicians play a major role in the risk stratification of patients with coronary artery disease (CAD) preparing for noncardiac surgery. Preoperative risk assessment takes into account the type and urgency of surgery and the extent of underlying CAD. With this approach, patients can be categorized as being at high, intermediate, or low risk for postoperative cardiac complications. Judicious use of preoperative noninvasive cardiac testing may help identify those patients at particularly high risk for such complications. PMID- 1409176 TI - Coronary artery disease in surgical patients. Perioperative management. AB - With effective communication, optimal use of perioperative therapeutic techniques, and postoperative follow-up, the medical, surgical, and anesthetic teams can prevent or minimize cardiac complications that occur during the postoperative period. Up to 50% of postoperative myocardial infarctions may be silent, or they may present as congestive heart failure, hypotension, or arrhythmia. Dyspnea is a common finding. All high-risk patients should be monitored in the intensive care unit during the first 7 days after surgery, when adverse cardiac events are most common. PMID- 1409177 TI - Anaphylaxis. How to manage and prevent this medical emergency. AB - Anaphylaxis is a dramatic, major medical emergency. Understanding of the pathogenesis, emergency treatment, and subsequent prophylaxis can reduce both morbidity and mortality. Treatment of anaphylaxis should begin with a high degree of suspicion. Taking a wait-and-see attitude in hopes that the reaction will be mild may have serious results. PMID- 1409178 TI - Delirium and acute psychosis. Mental states calling for clear diagnostic thinking and careful management. AB - Management of a delirious or acutely psychotic patient calls for rapid but well considered decision making by the treating physician. Clear diagnostic thinking is vitally important in making a presumptive diagnosis and forming a treatment plan. Appropriate treatment usually returns patients to a less agitated state and allows for definitive treatment of any underlying illness. PMID- 1409179 TI - Retrospective medicine. PMID- 1409180 TI - Gastrointestinal foreign bodies. When to remove them, when to watch and wait. AB - By being aware of which patients are at high risk for ingestion or insertion of foreign bodies, physicians can be on the lookout for objects in the gastrointestinal tract and ready to institute initial care. Esophageal foreign bodies and other objects that increase the chance of perforation or obstruction may require urgent endoscopic or surgical removal. Other objects may be expelled on their own. Identification of those that require early intervention is the key to successful management. PMID- 1409181 TI - 'Halloween diarrhea'. An unexpected trick of sorbitol-containing candy. AB - When a patient with severe diarrhea and flatulence is afebrile and the results of physical examination are negative, a food source should be suspected as the cause of the problem. Careful scrutiny of the patient's diet and a high index of suspicion may implicate the artificial sweetener sorbitol. Exclusion of sorbitol from the patient's diet is recommended in these cases before embarking on an extensive clinical investigation. PMID- 1409182 TI - Lead poisoning in children. The ramifications and the road to prevention. AB - Environmental lead poisoning is easier to prevent than to treat, and it can be destructive or deadly if ignored. Dr Schlenker, medical director of the Milwaukee Health Department, shares his approach to screening young children for potentially dangerous blood lead levels, educating the community about prevention of lead poisoning, and eradicating environmental sources of lead. PMID- 1409183 TI - Lead poisoning. Are your children at risk? PMID- 1409184 TI - In sickness and in health. PMID- 1409185 TI - Breast cancer. Improving your acumen in diagnosis. PMID- 1409186 TI - Evaluation of common breast masses. AB - Most breast lesions, including those that are malignant, are found by women themselves, which emphasizes the importance of breast self-examination. Comprehensive knowledge of breast anatomy and the characteristics that suggest that a mass is benign or suspicious aids primary care physicians in choosing the proper sequence of action. Drs Bland and Love discuss the common breast lesions and provide a detailed algorithm for management. PMID- 1409189 TI - Treatment of Raynaud's phenomenon with triiodothyronine corrects co-existent autonomic dysfunction: preliminary findings. AB - Cardiovascular autonomic function was assessed in 9 subjects with Raynaud's phenomenon. The underlying diseases were systemic lupus erythematosus (n = 5), systemic sclerosis (n = 3) and rheumatoid arthritis (n = 1). Five standard non invasive tests, 3 of heart rate and 2 of blood pressure, were employed. Compared with age and sex matched controls (n = 25), the number of values abnormal was 24 of 45 (53%) overall and between one and 4 (median, 2) individually. Significant differences were present for 3 tests, two of heart rate and one of blood pressure. The subjects were given triiodothyronine, 60 to 80 micrograms per day, for vasospastic attacks. Autonomic function was reassessed between weeks 4 and 9 (9 subjects) and between weeks 12 and 18 (8 subjects) after introduction of triiodothyronine. Test results showed a considerable improvement. At the second reassessment, the number of values abnormal was now 5 of 40 (12.5%) overall and nil (n = 4) or one (n = 4) individually. Significant differences remained for one heart rate test only. Adverse side effects to triiodothyronine occurred in a single subject and were readily controlled. Evidence of somatic neuropathy was present electrophysiologically in all 9 subjects and clinically in 8. Triiodothyronine may have corrected autonomic dysfunction by increasing blood flow to ischaemic peripheral nerves or by acting on the autonomic system more directly. Further study of triiodothyronine in autonomic insufficiency appears merited. PMID- 1409187 TI - Autoimmunity and glomerulonephritis. AB - Autoimmunity is now unequivocally regarded as the predominant pathogenic process underlying most forms of primary and secondary glomerulonephritis in humans. Most of the investigations so far have been focused upon humoral mechanisms. Consequently, the role of cell-mediated immunity in nephritis is still incompletely understood. Nonetheless, as a result of contemporary studies, a number of previously unidentified auto-antibodies in association with glomerulonephritis have been discovered. However, apart from anti-NC1 antibodies in the classical Goodpasture syndrome, the exact role of these auto-antibodies in the pathogenesis of glomerulonephritis yet remains undefined. This fact, however, does not undermine the relevance of exploring these auto-antibodies. They have been of immense help in sub-classifying glomerulonephritis previously thought homogeneous (Figure 3). Besides, analysis of auto-antibodies has assisted tremendously in the early diagnosis of rapidly progressive glomerulonephritis. This, in turn, has aided in early commencement of therapy thus contributing to regression in morbidity and mortality resulting from these disorders. Moreover, investigation of these auto-antibodies is of enormous value for future studies aimed at understanding the pathogenic mechanisms involved in glomerulonephritis. PMID- 1409190 TI - Lymphocytic adenosine deaminase activity in typhoid fevers. AB - Lymphocyte adenosine deaminase (L-ADA) activity, a measure of lymphocyte activity, was estimated in 10 healthy controls and 30 patients with typhoid fever (20 uncomplicated and 10 complicated) at the time of admission, at onset of complications and weekly until recovery. Mean L-ADA activity in healthy controls was 20.49 +/- 3.62 mU/10(6) cells. In uncomplicated patients L-ADA activity was 36.33 +/- 5.09 mU/10(6) cells at time of admission, which is significantly raised as compared to controls. It remained high at the height of the fever and at defervescence. In complicated patients L-ADA activity was significantly low at admission (15.33 +/- 2.35 mU/10(6) cells) and fell further with development of complications (7.86 +/- 4.07 mU/10(6) cells). At defervescence L-ADA activity increased significantly above the control activity (31.24 +/- 5.37). Serial L-ADA activity can be of prognostic significance. A cut-off value of 24 mU/10(6) cells is suggested to predict prognosis and severity of disease. Activity below this indicates a probability of a severe, prolonged course and may help in instituting early and energetic treatment. PMID- 1409188 TI - Molecular biology in medicine. PMID- 1409191 TI - Use of the SeHCAT test in the investigation of diarrhoea. AB - The SeHCAT test was used to investigate possible bile acid malabsorption in 166 patients presenting to a district general hospital with chronic diarrhoea of uncertain cause. Eighty-four (51%) patients had impaired SeHCAT retention. These included 23 of 28 patients with a possible type I abnormality (terminal ileal resection or disease, previous pelvic radiotherapy), 20 of 74 with a possible type II abnormality (idiopathic diarrhoea), 32 of 45 with a possible type III abnormality (post-cholecystectomy, post-vagotomy), and 9 of 19 with diarrhoea associated with diabetes. Patients with severe bile acid malabsorption demonstrated a good response to cholestyramine whereas the response in patients with a mildly abnormal SeHCAT retention was variable. Bile acid malabsorption is an important cause of diarrhoea in patients presenting with unexplained chronic diarrhoea. PMID- 1409192 TI - Vocal cord paralysis and oesophago-broncho-aortic fistula complicating foreign body-induced oesophageal perforation. AB - A 61 year old man died after presenting with a 24 h history of haematemesis and haemoptysis, and one year history of hoarseness of voice. Post-mortem examination showed a dental plate eroding through the mid-oesophagus into a bronchus and into the descending arch of the aorta, with scarring suggestive of old perforation. An organized haematoma also involved the left recurrent laryngeal nerve. Vocal cord paralysis may be a manifestation of foreign body-induced oesophageal perforation, which can lead to death from an oesophago-broncho-aortic fistula. Both complications of oesophageal perforation from a foreign body have not to our knowledge been previously reported. PMID- 1409193 TI - Horner's syndrome in severe tetanus. AB - A 66 year old man was admitted with a left Horner's syndrome, and trismus due to tetanus. Three days later he had respiratory arrests, classical tetanic spasms and was ventilated. He had associated severe autonomic dysfunction, tachyarrhythmias, hypotension, sweating and constipation. There was complete resolution of the left Horner's syndrome with recovery from tetanus. PMID- 1409194 TI - Falciparum malaria-induced hypoglycaemia in a diabetic patient. AB - We report a patient with diabetes mellitus who suffered severe falciparum malaria complicated by profound and persistent hypoglycaemia. The hypoglycaemia evolved before therapy with quinine was begun and resolved with eradication of the parasitaemia. The patient reverted to her baseline hyperglycaemia despite continuation of quinine. This case illustrates the critical role of falciparum malaria in the pathogenesis of malaria-associated hypoglycaemia, rather than quinine-mediated mechanisms. Anticipation of hypoglycaemia in falciparum malaria and its vigorous treatment may improve the poor prognosis associated with this complication. PMID- 1409195 TI - Life threatening hypophosphataemia in a patient with Philadelphia chromosome positive chronic myelogenous leukaemia in acute blastic crisis. AB - Life-threatening hypophosphataemia developed in a 47 year old woman with blastic crisis of chronic myelogenous leukaemia. The patient's hospitalization was characterized by reciprocal relationship between her white cell count and the serum phosphorus levels. The patient did not demonstrate any of the usual causes of profound hypophosphataemia. The postulated mechanism of this patient's hypophosphataemia is uptake by the rapidly dividing leukaemic cells. To the best of our knowledge this is the first case in the English literature of hypophosphataemia associated with blast crisis of Philadelphia chromosome positive chronic myelogenous leukaemia. PMID- 1409196 TI - Mitral stenosis in the Maroteaux-Lamy syndrome: a treatable cause of dyspnoea. AB - The case is reported of a young woman with the Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) who presented with rapidly progressive dyspnoea due to mitral stenosis. Mitral valve replacement was performed and the appearance of the valve was typical of mucopolysaccharide infiltration. Dyspnoea in patients with the Maroteaux-Lamy syndrome may be due primarily to cardiac valve involvement, and in this setting, valve surgery is safe and effective. PMID- 1409198 TI - Portal vein thrombosis in a complicated case of Crohn's disease. AB - Portal vein thrombosis is a rare complication of ulcerative colitis and is invariably fatal. This report describes a patient with severe Crohn's disease who underwent elective surgery complicated by an anastomotic disruption with faecal peritonitis. Following emergency laparotomy he developed left hypochondrial pain which was a manifestation of splenomegaly consequent upon portal vein thrombosis. Anticoagulation was successful in preventing further spread of the thrombosis as monitored by colour Doppler ultrasound. Severe active disease, surgery and sepsis have been recognized as predisposing factors for thromboembolic complications in inflammatory bowel disease and this patient was exposed to all three. It is conceivable that portal vein thromboses occur more commonly than suspected and ultrasound scanning could ascertain the prevalence if performed prospectively. PMID- 1409197 TI - Sotalol-induced torsade de pointes: management with magnesium infusion. AB - A 69 year old woman was treated with sotalol (320 mg daily) for intermittent atrial fibrillation. Sotalol was initially well tolerated and reversion to sinus rhythm with sinus bradycardia occurred 4 weeks after initiation of therapy. Shortly thereafter, the patient developed recurrent syncope due to torsade de pointes. This was treated successfully with intravenous magnesium infusion and withdrawal of sotalol. Subsequently, the atrial fibrillation was adequately managed using amiodarone, with no recurrence of torsade de pointes. Development of bradycardia associated with reversion to sinus rhythm represents a potential cause of 'late' pro-arrhythmic effects of sotalol. PMID- 1409199 TI - Pancreatic abscess due to Salmonella typhi. AB - Isolated involvement of the pancreas in Salmonella typhi bacteraemia is rare. A case of pancreatic abscess due to S. typhi is reported which was managed conservatively. PMID- 1409200 TI - Late presentation of a congenital gastric diverticulum causing pyloric obstruction. AB - We report a case of adult pyloric obstruction caused by the delayed presentation of a congenital gastric diverticulum. The derivation, classification and treatment of these abnormalities are discussed. PMID- 1409201 TI - Inguinal bladder hernia associated with vesico-ureteric reflux. AB - The urinary bladder is frequently found as a component of inguinal herniae. This report describes a case of 'bladder hernia' associated with vesico-ureteric reflux. The current methods of investigation and subsequent treatment for this condition are reviewed along with the possible underlying cause of vesico ureteric reflux in this case. PMID- 1409202 TI - Contamination of blood cultures. PMID- 1409203 TI - Homonymous hemianopsia and the 'door sign'. PMID- 1409204 TI - Constipation and colonic perforation complicating calcium resonium therapy. PMID- 1409205 TI - Rapid pulmonary cavitation due to Mycobacterium tuberculosis and infection with human immunodeficiency virus (HIV 1) PMID- 1409206 TI - Pseudogout associated with thyrotoxicosis. PMID- 1409207 TI - Morphine and severe dryness of the lips. PMID- 1409208 TI - Hypoglycaemia and heart failure. PMID- 1409209 TI - Cytolytic anticardiac membrane antibodies in the pathogenesis of myopericarditis. AB - Antisarcolemmal (ASAs) and antimyolemmal antibodies (AMLAs) are serological hallmarks of inflammatory heart muscle disease. They occur in a similar incidence in postcardiac injury syndromes, sarcoid heart disease or in dilated and hypertrophic cardiomyopathy. Rarely but still notably they are found with increasing age or in coronary artery disease. We therefore examined whether they are truly pathogenetic or whether they also possess properties of 'natural antibodies'. AMLAs and ASAs, like natural antibodies, have specificity for preserved structures on the membrane; they possess cross-reactivity and increase with age. In contrast to natural antibodies, however, they occur frequently after viral stimulation or other forms of trauma, are more often of the IgG and IgA than of the IgM isotype and fix complement in the acute stage of the disease. They also possess cytolytic and cytotoxic properties when incubated in vitro with isolated heart muscle cells. Antigenic mimicry has been demonstrated to be operative, since they are cross-reactive to viral proteins. PMID- 1409210 TI - The carditis/cardiomyopathy of rheumatic fever: relationship to pathogenesis. AB - Although the relationship between group A streptococcal upper respiratory tract infection and the development of acute rheumatic fever has been known for many years, the pathogenetic mechanism(s) have never been defined. Thus, the mechanism of damage to the valves and to the myocardium in patients with rheumatic fever remains unexplained. Traditionally, emphasis has been placed on the valvular damage in rheumatic heart disease, but there is considerable evidence for myocardial involvement. An abnormal immune response to some as yet unrecognized somatic or extracellular antigen of the group A streptococcus is probably related to the cardiomyopathy. This abnormal immune response is supported by considerable clinical and experimental evidence. Recent studies have suggested other mechanism to explain the myocardial damage including the influx of lymphocytes into the area as well as the possibility of damage relating to generation of oxygen-free radicals. As more sophisticated molecular biological studies of the group A streptococcus become available, perhaps the mystery of this very unique and common cardiomyopathy can be resolved. PMID- 1409211 TI - Positron-emission tomography and cardiomyopathy. AB - Because of its quantitative power and capacity to image biochemically unaltered tracers of physiological substrates, cardiac positron-emission tomography has emerged as a promising diagnostic modality and a powerful clinical research tool. It has enhanced characterization of the efficacy of diverse interventions designed to improve myocardial perfusion, differentiation of reversibly from irreversibly injured ischaemic myocardium, and detection of cardiomyopathic states. Progress in high rates of data acquisition, improved spatial and temporal resolution, accelerated image processing, and 3-dimensional display of images of myocardium offer promise for widespread applications to early detection of cardiac allograft rejection, graft atherosclerosis, and the efficacy of pharmacological interventions designed to protect recipients of cardiac allografts. PMID- 1409212 TI - Anticardiac antibodies in hypertrophic cardiomyopathy as a marker of severity. AB - Twenty-three patients (mean age 27 years, 15 male, 8 female) with hypertrophic cardiomyopathy (10 'obstructive', 13 'non-obstructive') mostly of the sporadic type were examined for anticardiac antibodies circulating in the peripheral blood or bound in the endomyocardial biopsy. Immunoglobulin deposition in the biopsies was found in 41% of cases of the IgG isotype. IgM and complement fixation occurred less frequently. Predominant findings in the patients sera were antimyolemmal (78%) and antifibril antibodies (43%). The patients' sera were not cytolytic except for one case indicating that neither a toxic serum factor nor antibody-mediated cardiocytolysis were operative to a significant degree in hypertrophic cardiomyopathy. The patient's lymphocytes did not demonstrate a cytotoxic effect either alone or in the presence of the autologous serum. PMID- 1409213 TI - Cardiomyopathies and specific heart muscle diseases. Definitions, terminology, classifications and new and old approaches. AB - Cardiomyopathies are defined as 'heart muscle diseases of unknown cause' and classified into hypertrophic, dilated and restrictive types, respectively. Hypertrophic cardiomyopathy is notable for massive ventricular hypertrophy without obvious cause, impaired diastolic and systolic function, a tendency for sudden death and a familial propensity. Dilated cardiomyopathy by contrast, demonstrates severe systolic failure progressing to congestive heart failure, with usually no familial tendency. Restrictive cardiomyopathy and diastolic heart disease represent syndromes with restriction to ventricular filling due to restrictive forces in the endomyocardium (and in constrictive pericarditis in the pericardium). The commonest cause of restrictive cardiomyopathy is endomyocardial fibrosis now usually known as hypereosinophilic endomyocardial disease. Specific heart muscle diseases are those conditions in which myocardial disease is due to a known cause: they usually produce systolic failure though occasionally a restrictive syndrome is evident. Amyloid heart disease occupies a place intermediate between cardiomyopathies and specific heart muscle diseases. The major features of the above conditions are described and current and future advances noted. Examples are the identification of the gene probably responsible for hypertrophic cardiomyopathy located on chromosome 14, and the identification of virus RNA particles in the myocardium in both myocarditis and in dilated cardiomyopathy, which strengthens the growing evidence suggesting that some cases of dilated cardiomyopathy may be due to previous myocarditis. PMID- 1409214 TI - Left ventricular involvement in right ventricular cardiomyopathy. AB - Right ventricular cardiomyopathy is generally considered a disease with isolated right ventricular involvement, although there are some case reports of concomitant abnormalities of the left ventricle. In order to evaluate the prevalence, characteristics and natural history of left ventricular involvement in this disease, 39 patients with right ventricular cardiomyopathy were studied by 2-dimensional echocardiography. At first evaluation 25 patients (group 1) showed right ventricular abnormalities and a normal left ventricle. In the remaining 14 patients (group 2) the right ventricular abnormalities were associated with left ventricular involvement (asynergic areas and/or mild diffuse hypokinesia). During the follow-up, left ventricular involvement appeared in 6 patients of group 1 and worsened in 4 patients of group 2. Five patients died. Pathological examination (available in 4 cases) showed, at the level of the right ventricle, marked atrophy of myocytes and fibro-fatty replacement, and predominant fibrosis at left ventricular level. Left ventricular involvement is thus frequent in right ventricular cardiomyopathy. At least in some cases the disease appears to be progressive. PMID- 1409215 TI - Endomyocardial biopsy: is it of clinical value? PMID- 1409216 TI - Controversial issues in restrictive cardiomyopathy. AB - The topic of restrictive cardiomyopathy remains controversial for many reasons. The term cardiomyopathy is unfortunately sometimes used interchangeably with diastolic heart failure. Furthermore, diastolic heart failure is sometimes linked with other causes of diastolic dysfunction such as hypertrophic cardiomyopathy and mitral valve disease. Restrictive cardiomyopathy is a clinical entity of primary or secondary myocardial disease presenting a picture that closely simulates that of constrictive pericarditis. In the majority of cases the correct diagnosis can be arrived at following a careful paradigm that begins with history and may end with endomyocardial biopsy. Many of the old teachings about how to distinguish restrictive cardiomyopathy from constrictive pericarditis have not held up with time and clinical experience: in particular equal diastolic pressures on both sides of the heart are compatible with either restrictive cardiomyopathy or constrictive pericarditis. PMID- 1409217 TI - Doppler echocardiographic evaluation of left ventricular diastolic function in patients with systemic sarcoidosis. AB - In order to estimate left ventricular diastolic function in systemic sarcoidosis, Doppler echocardiography was utilized in 10 normal female subjects (aged 45 +/- 13 years) and in 10 female patients (aged 48 +/- 14 years), with biopsy proven sarcoidosis and without any clinical evidence of other cardiac disease or hypertension. Left ventricular systolic function assessed by two-dimensional echocardiography was normal in both groups (ejection fraction greater than 60%). The following Doppler echocardiographic parameters were measured: peak early diastolic flow velocity (E), peak late atrial diastolic flow velocity (A), the ratio (E/A) and deceleration of the flow velocity in early diastole (E-F slope). The results showed that 5 patients had two or more abnormal Doppler diastolic indexes, indicating impaired left ventricular relaxation, while the remaining 5 patients had values within or just outside normal limits. The mean values for the patients as a whole showed increased A velocity (0.77 +/- 0.11 m/s versus 0.61 +/ 0.10 m/s; P + 0.05), decreased E/A ratio (1.05 +/- 0.32 versus 1.4 +/- 0.30; P + 0.01), normal E velocity and normal E-F slope, compared with the mean values of the normal group. We concluded that a large percentage (50%) of patients with systemic sarcoidosis, had reduced diastolic performance of the left ventricle, at a stage of the disease when systolic dysfunction is not yet evident. PMID- 1409218 TI - Anticoagulant treatment of atrial fibrillation in the elderly. AB - There is now adequate clinical evidence that the most appropriate treatment of elderly patients with non-valvular atrial fibrillation is with low dose warfarin. Patients may have contraindications to therapy with this agent, but should not be denied treatment based on age alone. Withholding treatment based on age places patients at unwarranted risk for severely disabling thromboembolic complications. PMID- 1409219 TI - Venous thromboembolism. AB - Pulmonary embolism is a complication of venous thrombosis. It is a major cause of morbidity and mortality, but a condition that is highly preventable and, when diagnosed, very effectively treated. Yet in the United States, more people die of pulmonary embolism each year than of AIDS. The clinician must maintain a high index of suspicion at all times in the patient at risk for this entity, keeping in mind that overall only about one-third of the patients suspected of having pulmonary embolism actually turn out to have it. A strong suspicion alone is not enough to warrant initiation of treatment, as a clinician must confirm with appropriate studies that venous thrombosis or pulmonary embolism is present. If studies of the lower extremities are negative, then a high probability ventilation perfusion scan (V/Q) or a positive pulmonary angiogram must be obtained before therapy should be considered. However, a high probability V/Q scan occurs in only 40% of patients with angiographically proven pulmonary embolism. Thus, if suspicion is high enough, do not accept a V/Q scan of 'indeterminate probability' as negative for pulmonary embolism. Even more important, though, is prevention of the disease with appropriate measures and that every individual who is at medium to high risk for development of deep venous thrombosis must have some kind of prophylaxis. PMID- 1409220 TI - The pathogenesis of dilated cardiomyopathy. AB - Using the WHO/ISFC definition and recommendations of nomenclature for cardiomyopathies, the aetiology is unknown. Over many years research has concentrated on defining pathogenetic mechanisms and owing to the widespread use of the bioptome-permitting recovery of fresh endomyocardial tissue-myocarditis has emerged as being intimately involved in the pathogenesis of dilated cardiomyopathy. In approximately 2,000 patients with a presumed diagnosis of dilated cardiomyopathy, myocarditis was found in 28% of these cases. The morphological diagnosis of myocarditis has been fraught with difficulties and, in attempt to establish criteria for its recognition, a group of cardiovascular pathologists (the author among them) met in Dallas in 1984. These criteria are detailed and categorization into acute, resolving (healing) and resolved (healed) has been emphasized because of important therapeutic implications. The cause of myocarditis has been established as being due to coxsackie B viruses. Up to recent times such findings could only be surmised by investigations such as micro neutralization tests. It was not until the hydridization probe was employed that direct proof was provided. These studies together with immunological consequences continue to be investigated in the hope of providing a rational approach to therapy. PMID- 1409221 TI - Effect of pyridoxine deficiency on immunological phenomena. AB - Measurements of serine hydroxymethyltransferase (SHMT) in resting lymphocyte cultures showed that the level of activity of this enzyme was very low. Under the influence of mitogenic stimuli serine hydroxymethyl-transferase activity was induced 5-20-fold. Addition in the cultures of 4-deoxypyridoxine, a potent antagonist of vitamin B6 coenzymes, concurrently with the mitogen, inhibits the induction of serine hydroxymethyltransferase. Thus deoxypyridoxine exerts its effects not only at the level of the enzyme itself by antagonizing the coenzyme but also at the level of its biosynthesis. Synchronous addition of vitamin B6 with deoxypyridoxine effectively reverses the inhibitory effects. The T helper cells of the lymphocyte culture are very sensitive to deoxypyridoxine action in contrast to T suppressor cells. The effect of phytohaemagglutinin or concanavalin A on the production of interleukin-1b, interleukin-2 and interleukin-2 receptors is profoundly affected by deoxypyridoxine. These results give a deeper insight of the mechanisms by which pyridoxine deficiency causes significant reduction of humoral and cellular immune responses to antigenic stimuli. On the basis of the data of this report a detailed illustration of the events that follow the T cell activation is presented. From this investigation the enzyme serine hydroxymethyltransferase emerges as a key element in the processes of immune responses and cell proliferation. Based on this finding we advance the following two propositions for possible future medical application: (i) combination of deoxypyridoxine with immunosuppressive drugs in case of immunosuppressive therapy or organ transplantation. (ii) the enzyme presents an excellent target for chemotherapy and therefore development of special agents directed against its apoprotein may prove to be a very valuable medical tool. PMID- 1409222 TI - Heart and heart-lung transplantation in the 1990s. AB - After 22 years of clinical application in our unit, heart transplantation is now an accepted therapeutic method. Its indications are well established, its surgical technique and post-operative control and treatment well defined, mostly due to better diagnosis of the rejection episodes with the aid of echocardiography and endomyocardial biopsy and the use of cyclosporin. The results are remarkable with a survival rate of 70% at 5 years, and a full rehabilitation into family, social and often professional life for almost all the survivors. Its use has dramatically changed the prognosis of patients with irreversible cardiac failure but underlines the lack of a sufficient number of donors' hearts. The heart-lung transplantation, making use of the progress of heart transplantation, has been used successfully since 1982 and for the first time in Europe by our group. Improvement in the selection of recipients, lung preservation, surgical technique and post-operative management have brought a new and real hope to patients not only irreversible cardiopulmonary lesions but also terminal pulmonary disease. PMID- 1409223 TI - Classification of turkeys as low or high volume semen producers using discriminant analysis. AB - Medium White turkeys in Generation 10 of divergent selection for semen ejaculate volume (SEV) were classified into lines that produce either low or high volumes of semen using a multivariate statistical technique, discriminant analysis. The discriminant function was based on records of hen fertility, embryonic mortality in the early and late incubation periods, and the incidence of pipped eggs. A hit ratio, the proportion of birds correctly categorized as low or high, of .60 was obtained. The discriminant function was subsequently used to classify birds in Generation 12. A misclassification rate of .28 and .48 was obtained for birds in the low and high lines, respectively. It was concluded that the relatively low rates of misclassification indicate a potential method for identifying male and female turkeys as belonging to low or high SEV lines, based on fertility and incubation records. PMID- 1409224 TI - Effects of photoschedule and strain cross on broiler performance and carcass yield. AB - The purpose of the present experiment was to examine possible interactions of strain cross and age with photoschedule for broiler performance and carcass yield. Day-old male broiler chicks from strain crosses of either Peterson x Arbor Acres (PA) or Ross x Arbor Acres (RA) were placed in light-controlled chambers (5.6 lx) with either 23 h light (L):1 h dark (D) from 1 to 56 days (Treatment E) or 6L:18D from 1 to 14 days and 1L:3D repeated from 15 to 56 days of age (Treatment BI). There were age by light treatment and age by strain cross interactions for BW; Treatment E had greater BW than Treatment BI from 7 to 42 days, and the PA cross BW was greater than the RA cross BW from 1 to 42 days of age. Cumulative feed efficiency was improved by Treatment BI compared with Treatment E up to 49 days. There were no differences among main effects for mortality, and the incidence of leg problems increased with age. Fillet and tender yields (per lean carcass weight) were higher for Treatment E than BI and opposite responses were seen for drumstick and thigh yields. The RA cross showed higher fillet and tender yields than the PA cross and the opposite relationship was found for drumstick and wing yields. PMID- 1409225 TI - Live performance and carcass yield of broiler strain crosses provided either sixteen or twenty-three hours of light per day. AB - The purpose of the present study was to compare a restricted (R) lighting program [16 h light (L):8 h dark (D)] with a standard extended (E) lighting schedule (23L:1D) for broilers. Experiment 1 was carried out during March and April (mean temperature of 23.3 C). Light treatments were 1) E; 2) R; 3) 16L:8D Days 1 to 21 and 23L:1D thereafter to 49 days (R3E); and 4) 16L:8D Days 1 to 14 and 23L:1D thereafter to 49 days (R2E). Treatments were factorially arranged with two strain crosses [Indian River x Arbor Acres (IA) and Peterson x Arbor Acres (PA)]. Experiment 2 was carried out during the summer (mean temperature of 27.0 C). Light Treatments E and R were factorially arranged with two strain crosses [Cobb x Arbor Acres (CA) and PA]. In Experiment 1, BW of Cross PA was greater than BW of Cross IA at 1, 14, 35, and 49 days of age. The percentage of birds with breast blisters was greater in Cross PA than IA. The incidence of broken clavicles was lower in Treatments R and R3E than in Treatments E or R2E. In Experiment 2, Treatment E had greater BW than R from 7 to 42 days of age, and BW of Cross CA was greater than that of PA from 1 to 48 days. Yield (percentage of lean carcass weight) of breast meat at 49 days of age was higher for Treatment E than R, and the percentage of birds with breast blisters was greater in Treatment R than E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409226 TI - Dietary supplementation with xanthophyll as an effective way of identifying low producing broiler breeder hens. AB - The relationship between dietary levels of xanthophyll, the degree of pigmentation in the hen, and egg production rate was studied in commercial broiler breeders (Anak 2000). In the first study, the degree of shank and beak coloration, measured with a 15-grade Roche yolk color fan, was determined in broiler breeder pullets until 34 wk of age. Although overall body coloration decreased with age following initiation of egg production, the degree of shank coloration was two- to threefold higher than that of the beak. In the second study, Roche Carophyll-red (canthaxanthin, 10%) was supplemented at levels of 0, 10, and 20 mg/kg in a corn and soybean diet containing xanthophyll, and given to hens for a period of 4 wk beginning at 55 wk of age. Increasing dietary canthaxanthin levels increased pigmentation of beak and egg yolk in a quadratic manner, whereas pigmentation increased linearly in the shank. The production rate was inversely related to the degree of shank and beak pigmentation. In a third study, the relationship between hen pigmentation (using Carophyll-red, 30 mg/kg of diet) and production rate was examined in a commercial flock of broiler breeder hens. Hens were sampled according to shank coloration (Grades 1 to 3) and egg production was monitored. The production rate of hens with high coloration was significantly lower (by approximately 33%) than the flock average. At peak production, shank pigmentation was too low to differentiate visually between degrees of coloration. Dietary supplementation of 5% corn gluten meal increased shank pigmentation and enabled efficient identification of the nonlaying hens. PMID- 1409227 TI - The effect of feed restriction and Eimeria maxima infection with or without medication on growth and feed intake in broilers. AB - Day-old male broiler chicks were raised in floor pens. At 4 days of age, birds in 75% of the pens were inoculated with Eimeria maxima via the feed. There were four dietary treatments: uninoculated, unmedicated control (UUC), infected, unmedicated control (IUC), infected, halofuginone-medicated (3 ppm, HM), or infected, salinomycin-medicated (66 ppm, SM). At 6 days of age, birds in 50% of the pens of each treatment were restricted for 5 days to their maintenance energy intake level. The remainder consumed feed ad libitum. Medication reduced growth from 0 to 6 days of age and feed intake was depressed, irrespective of medication, in infected birds from 0 to 21 days of age. Growth, however, was improved with intake of coccidiostat over IUC from 6 to 11 days of age but did not match UUC until 28 days of age. At 42 and 49 days of age, infected birds were lighter than UUC birds. Dressing percentage for HM and SM birds was greater than that of UUC birds at 49 days of age but HM birds also had a greater percentage of abdominal fat at both 42 and 49 days of age. Feed restriction resulted in some compensatory growth immediately following refeeding. Experimental feed:gain ratio was improved in restricted birds (1.98 versus 2.03 g:g). At 42 and 49 days of age, restricted birds were lighter than birds eating ad libitum and also had a significantly greater percentage abdominal fat. A lower breast yield was observed at 42 days of age in restricted birds. PMID- 1409228 TI - Effects of two nipple drinker types with different flow rates on the productive performance of broiler chickens during summerlike growing conditions. AB - Three trials were conducted to study the effects of a high flow volume (2.3 mL/s) nipple waterer (HFN) versus a low flow volume (.4 mL/s) nipple waterer (LFN) on the productive performance of broiler chickens as measured by average body weight (kilograms), average feed conversion (kilograms:kilogram), and percentage mortality rate. Equal numbers of male and female birds were used during Trial 1; only male birds were used during Trials 2 and 3. All trials were conducted during the summer months. An attempt was made during Trial 2 to expose the birds to artificial heat stress. No differences were seen during any of the trials in feed conversion between the two treatments. In Trial 1 the only significant difference (P less than or equal to .05) exhibited was in average male body weight (1.87 kg HFN; 1.84 kg LFN). A highly significant difference (P less than or equal to .01) was seen in average body weight (1.75 kg HFN; 1.64 kg LFN) during Trial 2. Average body weight difference during Trial 3 was highly significant at 42 days of age but not at Day 49. Mortality rate figures during Trial 2 indicate a highly significant difference during the 38-day period prior to heat stress (2.2% LFN; .4% HFN), and significant difference during the heat stress period (38 to 44 days; 2.9% LFN; 1.5% HFN). During Trial 3 mortality rate differences were significant by 49 days (20.6% LFN; 11.4% HFN) although there was no difference at 42 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409229 TI - Effect of coccidiosis on the distribution of dietary lutein in the chick. AB - A series of experiments was run to determine whether the distribution of dietary carotenoids in chick plasma and tissue was dependent upon a saturable carrier, and to observe how infection with Eimeria acervulina affected this distribution. Broiler (Hubbard x Hubbard) and Sex Sal (Rhode Island Red x White Rock) chicks were fed a white corn and soybean meal-based diet supplemented with varying levels of a commercial lutein concentrate. Plasma, small intestine, and liver were analyzed for lutein. In the first experiment, mean plasma values in control broiler chicks increased linearly from 0 to 200 ppm supplementation. Mean plasma values of infected chicks were decreased an average of 71% as compared with controls, and reached a plateau between 100 and 200 ppm dietary lutein. In the second experiment, plasma, small intestinal, and liver lutein levels in broiler chicks reached a plateau between 200 and 500 ppm. In the third experiment, plasma and liver values in Sex Sal chicks leveled off between 250 and 500 ppm whereas levels in the small intestine increased linearly. Infection of the Sex Sal chicks at 3 wk of age with E. acervulina caused plasma lutein levels to be reduced about 88%, small intestinal levels 76%, and liver levels 72%. Supplementation with 500 ppm resulted in higher proportions of lutein in tissues. Infection with E. acervulina shifted the ratios to even higher proportions in the tissues at all supplementation levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409230 TI - Fermentation of [14C]lactose in broiler chicks by cecal anaerobes. AB - Volatile fatty acids and lactic acid were products of [14C]lactose metabolism in 10-day-old broiler chicks. The [14C]lactose and unlabeled lactose were given to chicks in combination with cultures of cecal anaerobes (direct fed microbials) from adult broiler chickens. Aliquots of these cecal anaerobes had been used previously to reduce Salmonella typhimurium colonization in broiler chicks. In the current study, chicks were treated with anaerobes and anaerobes plus lactose on the day of hatch. Chicks given lactose plus anaerobes also received unlabeled lactose in the drinking water. Chicks in all treatment groups received [14C]lactose on Day 10 posthatch. After 5 h, most of the radiolabel was detected in the foregut and intestine. Significantly lower concentrations of [14C]lactic acid were detected in the serum and foregut of chicks given anaerobes and anaerobes plus lactose than in the similar samples from control chicks. Additionally, significantly less [14C]lactic acid was detected in the feces of chicks treated with anaerobes plus lactose than in feces from control chicks and chicks receiving only anaerobes. Significant differences in the total content of volatile fatty acids and lactic acid were detected in the serum, liver, intestine, and ceca of chicks treated with anaerobes or anaerobes plus lactose. These data indicate that cecal flora utilize lactose to produce volatile fatty acids and lactic acid. PMID- 1409231 TI - Influence of increasing photoperiod and toe clipping on breast buttons of turkeys. AB - Two 17-wk experiments compared the effects of an increasing photoperiod treatment (INC) versus a constant photoperiod treatment (23H), and intact toes versus clipped toes, on the breast button incidence and performance of heavy tom turkeys. Under INC, the photoperiod was increased gradually from 8 to 23 h between 4 and 16 wk. Under 23H, the photoperiod remained constant at 23 h. Use of INC versus 23H resulted in a significant reduction in breast button incidence at 17 wk in both experiments (P less than .05). Toe clipping had no effect on breast button incidence. The presence of breast buttons was positively correlated with body weight at 12 wk, and area of unfeathered skin over the keel at 17 wk. In Experiment 1, the photoperiod treatments had no significant effect on 17-wk body weight or mortality, but the INC treatment had an adverse effect on feed efficiency (P less than .05). In Experiment 2, turkeys reared under INC were heavier at 17 wk (P less than .05), with similar feed efficiencies. Mortality was significantly lower on INC than 23H up to 12 wk in Experiment 2 (P less than .05). Turkeys with intact toes were .44 kg heavier than turkeys with clipped toes at 17 wk in both experiments (P less than .05) and had similar feed efficiencies. Mortality to 4 wk was lower for turkeys with intact than clipped toes in Experiment 2 (P less than .05). Increasing photoperiod treatments have potential for improving turkey performance, survival, and carcass quality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409232 TI - Evidence that bacteria are not causative agents of stunting syndrome in poults. AB - Two experiments were conducted to determine the effect of removing bacteria, including long segmented filamentous organisms (LSFO), from inoculum known to induce stunting syndrome (SS) in poults. Experiment 1 consisted of two identically designed trials. In each trial, each of four treatments was assigned to an isolator. Three treatments consisted of dosing, by crop intubation, groups of 1-day-old poults with unfiltered SS inoculum or filtrate of inoculum passed through .45- or .20-micron microfilters. Uninoculated poults were dosed with inoculum carrier, saline. Experiment 2 was done in battery facilities. Three rooms were used and each room housed one of three treatment groups. Triplicate pens of 10 poults each within each room were dosed by crop intubation with saline (uninoculated), unfiltered inoculum, or filtrate from .20-micron filtration. As compared with uninoculated poults, weight gain through 7 days was reduced 20% (P less than .05) by unfiltered and filtered inocula in both experiments. Jejunal maltase activity also was decreased (P less than .01) by unfiltered and filtered inocula. Feed efficiency (FE) was not determined in Experiment 1, but in Experiment 2, FE from 1 to 14 days of age was impaired by inoculum, irrespective of filtration. This effect was not evident during the 14- to 20-day period. The observation that the adverse effects of giving filtered inoculum to poults were the same as those caused by unfiltered inoculum indicated that bacteria, including LSFO, were not primary causative agents of the SS experimentally induced in poults. PMID- 1409233 TI - Effect of age and sex on true digestibility of amino acids of rapeseed and soybean meals in growing broilers. AB - Studies were conducted to evaluate the influence of age and sex of birds on true digestibilities of protein (TDP) and amino acids (TDAA) of two rapeseed meals and a soybean meal. Sixty-four broilers (50% of each sex) were used both in the first (at 3 wk of age) and the second trials (on the same animals at 6 wk of age). At the end of 3 and 6 wk of age, the birds were fasted for 24 h and then force-fed with moistened diets (diet:water: 50:50) approximately 40 and 90 g, respectively. Excreta were collected during the two 24-h periods after force-feeding. The TDP and TDAA of rapeseed and soybean meals decreased significantly as the age of broilers increased from 3 to 6 wk. At 3 wk of age, the TDP and TDAA were not influenced by the sex of the animals. At 6 wk of age, the TDAA of the two rapeseed meals was higher in males than in females. The TDAA of soybean meal did not vary with sex. Sex had no effect on the TDP values of the three raw materials tested. PMID- 1409234 TI - Measurement of metabolizable energy in poultry feeds by an in vitro system. AB - A two-stage in vitro system (IVDE) for estimating AMEn in poultry feeds was investigated. For 71 diets ranging from 2.2 to 3.4 kcal/g, the average AMEn was 2.889 kcal/g and the mean IVDE value was 3.005 kcal/g. From the 71 diets, 30 (42.2%) showed differences between AMEn and IVDE of less than .100 kcal/g and represented diets across the AMEn range of values. The statistical analysis of the data showed a standard error of the estimate (SEE) of .152 kcal/g for the 71 diets assayed. No clear differences in accuracy of AMEn among the diets, as related to the composition and proportion of ingredients, were observed. Thus, the IVDE method gave different AMEn for diets of similar composition. The application of the IVDE system to selected ingredients showed that the AMEn of corn was underestimated by the method. However the AMEn of roasted, extruded soybeans and oats was estimated accurately by the IVDE method. Other ingredients were greatly overestimated by the in vitro technique (soybean meal, corn gluten meal, and barley). The results of applying the IVDE method for estimating AMEn showed the limitations of this technique with regard to the universality of its application. Although the method was successful in estimating AMEn values of diets and ingredients, for many samples the IVDE technique did not give acceptable results. PMID- 1409235 TI - Effect of dietary polyunsaturated fatty acid concentration on performance, fat deposition, and carcass fatty acid composition in broiler chickens. AB - The effect of dietary polyunsaturated fatty acid (PUFA) concentration on body fat deposition and composition in broiler chickens was studied. Twenty-day-old birds were fed five isocaloric diets supplemented with different combinations of tallow and vegetable oils. Contents of abdominal adipose tissue (AAT) as well as body fat were determined at 40 days of age. A significant linear effect was observed between dietary PUFA and feed utilization. Fatty acid (FA) profiles in AAT and total body fat were correlated to dietary PUFA content, with the main effect of higher dietary PUFA being a reduction in monoenoic FA (C16:1 and C18:1) and an increase in C18:2. The effect of dietary PUFA on the saturated FA (C16:0 and C18:0) was small and not statistically significant. Increased dietary PUFA modified FA composition such that C18:2, rather than C18:1 became the dominant FA in AAT. In that respect, greater changes were observed in FA composition of AAT, as compared with that on the whole carcass. The deposition of saturated and monoenoic FA in the whole carcass during the experimental period was related to dietary PUFA content in a quadratic manner. However, deposition of C18:2 and C18:3 was not affected by intake and their utilization (deposition:intake ratio) was reduced in a manner parallel to their dietary levels. PMID- 1409236 TI - Influence of dietary n-6 and n-3 polyunsaturates on lipids in chickens divergently selected for body weight. AB - The effects of dietary lipid sources rich in n-6 (soybean oil) or n-3 (menhaden oil) polyunsaturated fatty acids (PUFA) on blood triacylglycerol levels and tissue fatty acid compositions in female chickens from two genetic lines were examined. Triacylglycerol concentrations in the plasma very low density and low density lipoprotein fractions were elevated in the low-weight (LW) chickens compared with the high-weight (HW) group. Chicken heterophil to lymphocyte ratios and total antibody titers to sheep red blood cells at 84 days were not influenced by genetic line or by the dietary lipid fed. Concentrations of C18:1 fatty acid isomers and total monounsaturates were highest in liver and heart tissues of HW chickens. Feeding menhaden oil enriched the plasma, liver, and heart with n-3 PUFA in both genetic lines. The data indicate a difference in hepatic fatty acid metabolism between the HW and LW lines that is unaffected by dietary n-6 or n-3 PUFA. PMID- 1409237 TI - Morphological study of the dove spleen. AB - The spleen and vascular resin cast from doves were observed by a light and a scanning electron microscope for the purpose of studying the histological structure and the mode of the splenic blood microcirculation. The trabeculae of the dove spleen were poorly developed and the white and red pulps could not be distinguished from each other as is also the case of the chicken spleen. The luminal surface of the sinus was covered by continuous endothelial cells that had nuclear protrusion into the lumen. The blood cells passed to the sinus via the small gap of the luminal surface of the sinus. Irregular resin masses that connected the terminal portion of the artery with the venous sinus were observed. The direct connection between the arterial terminalis and venous sinus could not be recognized. When the resin was injected retrograde to blood flow from the vein, the sinus ended blindly. PMID- 1409238 TI - A method of analysis of the electrical activity of the proximal gastrointestinal tract of the chicken. AB - The present paper describes a method of recording and analyzing electromyographical (EMG) signals from the digestive tract of the chicken. The EMG signals from the proventriculus, gizzard, and duodenum were recorded after implantation of Ni and Cr electrodes. The amplified EMG signals were digitized using a sampling frequency of 50 samples per second, and numerical data was stored immediately on the hard disk (1 datum = 1 byte). The software designed allowed: 1) detection of spike-bursts with a high accuracy; 2) analysis of maximum amplitude (with a maximum error of 6.7%), mean amplitude, duration, and frequency of the spike-bursts; the time of interval between spike-bursts, and the percentage of activity; 3) integration of the recorded data with a variable time set; and 4) a wave analysis by means of the Fourier algorithm. These methods, already used in EMG studies in mammals, are assembled and adapted for its application in birds. PMID- 1409239 TI - A quantitative chemical study of the comb and wattle galactosaminoglycans from single comb White Leghorn roosters. AB - Galactosaminoglycans from mature rooster comb and wattle tissues were separated into five fractions by ethanol precipitation. An average of 90% total uronic acid was recovered in Fractions I to III. Fractions I and II were dermatan sulfate with relatively high proportions of L-iduronic acid (61 to 80%), but this uronic acid was a minor component (30%) in Fraction III, in which D-glucuronic acid was the major uronic acid. Digestion with testicular hyaluronidase suggested that most if not all of the galactosaminoglycans in Fractions I to III were copolymers containing both L-iduronic acid and D-glucuronic acid. Fractions IV and V contained much lower proportions of L-iduronic acid and showed broader electrophoresis bands than did Fraction III. PMID- 1409240 TI - Research note: age-dependent changes in 3-oxy-methyl-D-glucose and leucine intestinal absorption in chickens. AB - Intestinal absorption of 3-oxy-methyl-D-glucose (3-OMG) and leucine were studied in intestinal slices from fasted 1-, 2-, and 3-wk-old chickens. The intestinal segments studied were the duodenum, jejunum, ileum, and cecum, with the latter divided into proximal and medial regions. There was a decrease in the intestinal absorption of 3-OMG and leucine in the duodenal, jejunal, and proximal cecal segments with increasing age of the chicken. The medial cecum did not show age dependent differences in the uptake of substrates. In the ileum, there was a decrease in intestinal absorption of 3-OMG and leucine between Weeks 1 and 2, but thereafter the uptake was similar to that of the 2nd wk. PMID- 1409241 TI - Research note: eggshell quality in Japanese quail fed different fatty acids. AB - The purpose of the present study was to determine the effects of diets containing 3% palmitic acid (Diet PA), oleic acid (Diet OA), or linoleic acid (Diet LA) on the shell quality of eggs of Japanese quail. Each diet was fed to 10 hens maintained individually in wire quail laying cages. There was no difference (P greater than .05) in feed consumption between hens fed Diets OA and LA, but hens of both groups consumed less (P less than .05) feed than those fed Diet PA. Egg weight, shell weight, and thickness of shell plus membrane were not influenced by dietary treatment (P greater than .05). However, specific gravity of eggs from hens fed Diet OA was significantly higher (P less than .05) than that of eggs from those fed either Diet PA or Diet LA. Comparison of these data with hatchability data obtained in a previous experiment conducted under similar conditions suggests that the differences in hatchability would not be explained by differences in eggshell quality. PMID- 1409242 TI - Research note: efficacy of various flavonoids and simple phenolics in prevention of nutritional myopathy in the chick. AB - A 33-day feeding experiment was conducted with 3-day-old broiler chicks to assess the efficacy of various flavonoid and simple phenolic antioxidants in preventing nutritional muscular dystrophy (NMD) resulting from vitamin E deficiency. None of the flavonoids or simple phenolics at a dietary concentration of 1,000 ppm completely prevented NMD but quercetin reduced (P less than .05) its incidence and quercetin, morin, and ferulic acid reduced (P less than .05) the severity of the disorder. The low-selenium, low-vitamin E diet also promoted the development of a mild exudative diathesis (ED) in many of the birds, which was inhibited (P less than .05) by the rutin and silymarin treatments, but exacerbated (P less than .05) by quercetin, morin, and ferulic acid. Changes in concentrations of vitamin E in plasma, liver, or muscle, caused by the various treatments (other than vitamin E), were not related to protection against NMD or ED. PMID- 1409243 TI - Effects of amiloride on the cardiovascular system: role of Na+/Ca2+ exchange. PMID- 1409244 TI - Effects of intranasal neostigmine on oesophageal motility in man. AB - The effects of intranasally administered neostigmine on oesophageal peristalsis and lower oesophageal sphincter tone were investigated in 21 healthy volunteers. After 30 min of basal recording of oesophageal tracings, neostigmine (3 or 5.4 mg) or the inert vehicle were given. The oesophageal recording was continued for 45-60 min after administration. Neostigmine increased the amplitude and duration of the peristaltic waves without significantly affecting conduction. Lower oesophageal sphincter tone was also increased but post-swallowing relaxation was normal. At the highest dose, the effects of neostigmine lasted 45 min or more. There were no side effects and the heart rate was only slightly slowed. The results suggest that intranasal administration of neostigmine might be clinically useful for stimulation of upper gastrointestinal tract peristalsis. PMID- 1409245 TI - Pteroylpolyglutamate pool modifications in rat liver after chronic administration of phenobarbitone and valproate. AB - Chronic intraperitoneal administration of low doses of phenobarbitone and valproate caused different alterations in hepatic percentage distribution of pteroylpolyglutamate derivatives without modification of total folate content. Phenobarbitone treatment caused a significant decrease of the percentage content of reduced unsubstituted and methylene-substituted derivatives, while valproate produced an increase of the percentage content of methenyl-, formyl- and formimino-substituted derivatives and a concomitant percent increase of hexaglutamates. The modified ratios of various pteroylpolyglutamates, both in phenobarbitone- and in valproate-treated animals, probably contribute to influencing the partitioning of the one-carbon pool through the various areas of one-carbon metabolism. PMID- 1409246 TI - Graphical analysis of data from pharmacology experiments. AB - Dose-response curves are often used in the study of the interaction of hormones and receptors. From these plots, IC50 or EC50 values are calculated. In these pharmacological assays it is implicitly assumed that a single receptor predominates in a tissue. In this paper the interaction of a ligand with two receptors is studied from a theoretical point of view. It is assumed that the responses mediated by these receptors are qualitatively or quantitatively different. The theoretical direct and Scatchard plots display a high variety of shapes depending upon the difference in potency of the effect of the drug acting in both receptors and upon the magnitude and sign of the individual response. When dose-response curves taken from the literature have been transformed into direct or Scatchard plots new information has become available. With respect to this, it is shown that agonists of purinergic receptors seem to interact with two different populations of receptors. We claim that carefully designed experiments must provide valuable information concerning the number of subtypes of receptors present in a given system and the kind of response mediated by them. PMID- 1409247 TI - Lack of inhibition of ornithine decarboxylase activity by ibuprofen. AB - The influence of the anti-inflammatory drug ibuprofen on the activity of ornithine decarboxylase (ODC, EC 4.1.1.17), the key enzyme of polyamine synthesis, was studied using a 20,000 g supernatant of rat testis and regenerating liver homogenates as sources of the enzyme. Ibuprofen, in all concentrations studied (10(-6) to 2 x 10(-3) M), did not influence either testicular or hepatic ODC activity in vitro. The role of ODC in inflammatory processes and the lack of ODC inhibition by ibuprofen are discussed in view of the controversial findings of other authors. PMID- 1409248 TI - Activation of the Langendorff perfused rat heart depolarized by increased external potassium concentration. AB - Myocardial activation under depolarized conditions was studied in spontaneously beating Langendorff perfused hearts from albino rats. Depolarization was obtained by increasing external potassium concentration in steps (5.4, 7.4, 10, 10.5, 11 and 11.5 mM) in the perfusing solution with or without adrenaline (Adr). Left ventricle isovolumic systolic pressure and coronary flow did not change as external potassium increased, albeit being larger with Adr in the perfusing solution. Atrial and ventricular rates decreased, the latter showing a larger decline. The same behaviour was displayed by perfused hearts, with higher rates being developed by the group with Adr. PR interval and QRS complex duration increased as a function of external potassium. PR intervals were the same in both groups but QRS duration was larger in the Adr group, indicating that AV conduction was not changed in presence of Adr but intraventricular conduction was delayed in that situation. It was also observed that in the great majority of perfused hearts, differing from isolated preparations, ventricular mechanical activity ceased at around 11.5 mM external potassium. PMID- 1409249 TI - In vitro activity of sulphimidazole alone and in association with trimethoprim against enteric pathogens. AB - Sulphimidazole is a new sulphonamide belonging to the class of intestinal sulphonamides and characterized by the fact that it is active even in vitro. It has the heterocyclic ring of 5-nitroimidazoles on amidic nitrogen. Its antibacterial activity is similar to that of the classical sulphonamides but differs in that it also combats certain anaerobic bacteria such as Clostridium botulinum. This effect is completely absent in the case of sulphadiazine and sulphamethoxazole. Also, since p-amino-benzene-sulphonamide is present in the molecule, the drug acts in synergism with trimethoprim against certain aerobic or facultative strains of enteric pathogens. PMID- 1409250 TI - Role of aldehyde dehydrogenase in the biological activity of spermine dialdehyde, a novel immunosuppressive/purging agent. AB - The antitumour and immunosuppressive activities of spermine dialdehyde (SDA), a synthetic, oxidized form of spermine, were examined using L1210 cell lines and murine bone marrow cells. SDA acted as a high affinity substrate for aldehyde dehydrogenase (ADH) derived from different sources, with kinetic profiles similar to other aldehyde substrates. The murine leukaemic, cyclophosphamide-resistant L1210/CPA cells, having high levels of intracellular ADH activity, were less sensitive to SDA compared to ADH deficient L1210/O cells as measured by [3H] thymidine incorporation in proliferation studies. Furthermore, pretreatment of L1210/CPA cells with the ADH inhibitor, diethyl aminobenzaldehyde (DEAB), resulted in potentiation of the SDA response. Murine bone marrow cells were more resistant to SDA than splenic T cells. However, addition of DEAB to bone marrow cultures potentiated the sensitivity of progenitor cells to SDA, as measured by colony formation. The results indicate that levels of ADH in the target tissues would determine the potency of SDA and subsequently offer selectivity and specificity to the therapeutic potentials of this putative purging agent. PMID- 1409251 TI - Release of atrial natriuretic factor induced by the A1 adenosine receptor agonist 2-chloro-N6-cyclopentyl-adenosine in the rat. AB - The effect of the adenosine receptor agonists, 2-chloro-N6-cyclopentyladenosine (CCPA) and 2-hexynyl-adenosine-5'-N-ethylcarboxamide (HENECA) on atrial natriuretic factor (ANF) release was investigated. The A1 adenosine receptor agonist CCPA markedly increased plasma ANF levels, following subcutaneous (s.c.), but not intracerebroventricular injection. ANF release evoked by the s.c. injection of CCPA was completely abolished by s.c. pretreatment with the selective A1 adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine. The A2 adenosine receptor agonist HENECA did not produce ANF release. The results of the present study suggest that peripheral adenosine mechanisms might be involved in the control of ANF secretion, through the activation of A1 adenosine receptors. Preliminary results show that CCPA produces ANF release also from isolated atria, thus suggesting that its action on ANF release is, at least in part, direct, and not only a consequence of cardiovascular modifications. PMID- 1409252 TI - Is inotropic therapy for heart failure an unfulfilled promise? PMID- 1409253 TI - Purinergic receptors, prostacyclin and atherosclerosis. PMID- 1409254 TI - Neuropsychopharmacological study of 2,4-dihydro[1,2,4]triazolo[3,4 c][1,4]benzothiazine-1-one (IDPH-791). AB - The neuropsychopharmacological profile of a new centrally acting skeletal muscle relaxant, 2,4-dihydro[1,2,4]triazolo[3,4-c][1,4]benzothiazine-1-one (IDPH-791), an analogue of triazolobenzothiazine, has been described and compared to mephenesin, a well known centrally-acting muscle relaxant. IDPH-791 was found to be safer and of longer duration of action than mephenesin in all the tests conducted in this study. Both IDPH-791 and mephenesin caused ataxia, decrease in spontaneous activity and inhibition of pinnal reflex. IDPH-791 was 1.5 to 2.0 times more potent in exhibiting motor inco-ordination and anticonvulsant activity than mephenesin in mice and rats. IDPH-791 was twice as active in inhibiting various spinal polysynaptic reflexes, crossed extensor, flexor, and linguomandibular reflexes; however, both did not affect the typical monosynaptic reflex, patellar reflex. IDPH-791 and mephenesin did not have sedative activity. Although mephenesin exhibited haemolytic activity, IDPH-791 was devoid of this activity. It is concluded that IDPH-791 is a safe and effective centrally-acting muscle relaxant having a longer duration of action than mephenesin. IDPH-791 is also devoid of sedative and haemolytic activity. PMID- 1409255 TI - Cardiotoxicity induced by doxorubicin in vivo: protective activity of the spin trap alpha-phenyl-tert-butyl nitrone. AB - The role of free radical generation in the development of the acute cardiotoxicity induced by doxorubicin (DXR) in the rat and the protective activity of anti-radical drugs were investigated in in vivo experiments by evaluating the body weight curve, ECG, contractile performance and coronary flow up to 10 days after DXR. A lipophilic spin trap (alpha-phenyl-tert-butyl nitrone, PBN) was continuously administered at a dose of 0.65 mg/kg every hour for 2 weeks by an intraperitoneal osmotic pump. DXR was administered i.v. at a dose of 9 mg/kg 3 days after beginning the PBN infusion. DXR impaired ECG and body weight gain after 3 days (partly reversible at later times), while contractility and coronary flow were significantly impaired throughout the experimental time. PBN was shown to prevent the DXR-induced alterations of contractility and coronary flow, while ECG was non-significantly improved. The body weight curve was not affected. Since the dose of PBN used does not produce pharmacological effects, the protective activity in rats receiving DXR indicates that free radicals may play a causal role in the acute cardiotoxicity in vivo. The use of suitable spin traps and administration schedules seems to be an interesting approach for the prevention of radical-dependent pathologies. PMID- 1409256 TI - A study of the neuronal and non-neuronal stores of dopamine in rat and rabbit kidney. AB - The present study has examined the effects of 6-hydroxydopamine (6-OHDA) alone and in combination with pargyline, desipramine and GBR 12909 and denervation as induced by occlusion of the renal artery (RAO) on the endogenous dopamine (DA) and noradrenaline (NA) contents in rat and rabbit renal tissues; the effects of chemical denervation on catecholamine levels in the left ventricle were also studied. In rat and rabbit renal medulla and rat renal cortex, 6-OHDA and pargyline plus 6-OHDA selectively reduced NA (85-92% reduction) without a parallel decrease in DA tissue content (19-27% reduction). This 6-OHDA- and pargyline plus 6-OHDA-insensitive DA pool was found to be resistant to denervation as induced by RAO. The NA-depleting effect of 6-OHDA in these renal areas was found to be prevented by the previous administration of desipramine, but not with that of GBR 12909. In the rabbit renal cortex, 6-OHDA selectively reduced NA (90% reduction) without a parallel depletion of DA (20% reduction); previous treatment with pargyline abolished this selectivity. Again, only desipramine, but not GBR 12909, was found to prevent the NA and DA depleting effect of 6-OHDA in the rabbit renal cortex. Denervation induced by RAO was also found to produce a parallel depletion of DA and NA tissue levels in this renal area. In the left ventricle, 6-OHDA alone or in combination with pargyline produced a parallel depletion of DA and NA tissue levels (79-88% reduction) in both species. These results provide evidence against the presence of independent dopaminergic neurones in rat and rabbit kidney and suggest that in rat and rabbit renal medulla and rat renal cortex most of DA is stored in a non-neuronal compartment; in rabbit renal cortex some of the DA appears to be located in noradrenergic neurones, in a store different from that which contains NA. PMID- 1409257 TI - Splanchnic haemodynamic effects of ketanserin in anaesthetized cirrhotic rats. AB - The effects of ketanserin, atenolol and their association on portal vein pressure (PVP), portal and caval bile acid concentrations (PBA and CBA), and extraction ratio of bile acids (ER) after oral loading with chenodeoxycholic acid were investigated in anaesthetized cirrhotic rats. PVP was significantly reduced by ketanserin and by the association ketanserin plus atenolol; PBA was significantly decreased in all the treated groups, whereas the reduction of CBA was significant only in the rats treated with ketanserin and atenolol alone. ER was increased by atenolol and ketanserin, but it was not modified by their association. Moreover, a significant correlation was observed between PBA and CBA and between PVP and ER. These results suggest that, in anaesthetized cirrhotic rats, ketanserin reduces PVP probably through more complex mechanisms than the simple indirect reduction of portal flow, and that the association of ketanserin plus atenolol has no additive effect in reducing PVP. PMID- 1409258 TI - The effects of S(-) and R(+) sulpiride, metoclopramide, cisapride and domperidone on the small intestine suggest DA2-receptors are involved in the control of small intestinal transit time in rats. AB - To study the effect of intraperitoneal S(-)sulpiride (1-15 mg/kg), R(+)sulpiride (5-10 mg/kg), metoclopramide (1-15 mg/kg), cisapride (10 mg/kg) and domperidone (5-10 mg/kg) on intestinal progression, rats were given the test drug followed by oral lactulose. Their hydrogen excretion was used to calculate the small bowel transit time (SBTT) and maximum peak time (MPT). Metoclopramide (7.5 mg/kg) had the greatest effect on SBTT (-25%), followed by S(-)sulpiride and domperidone. S( )sulpiride (10 mg/kg) had the greatest activity on the MPT (-35.2%) followed by metoclopramide. R(+)sulpiride and cisapride did not modify SBTT and MPT. In conclusion S(-)sulpiride is the isomer active on intestinal transit and DA2 receptors seem important targets in the modulation of intestinal progression, since S(-)sulpiride, metoclopramide and domperidone are DA2-receptor antagonists, and R(+)sulpiride and cisapride are not. The H2 breath test proved a valid method for measuring the effect of drugs on the small intestine in animals. PMID- 1409259 TI - Non-serotonergic 3H-ketanserin binding sites in human platelets: characteristics and interaction with calcium antagonists. AB - Here we report the identification of binding sites for 3H-ketanserin in human platelet membranes. At 4 degrees C, 3H-ketanserin binding is saturable (Bmax = 0.58 pmol/mg protein), rapid (equilibrium being attained within 20 min) and reversible. The kinetics of the association and dissociation curves are consistent with the existence of a single class of binding sites, as confirmed also by computer-assisted analysis of the saturation curve. Specific binding is increased by Ca2+ and Mg2+. 3H-ketanserin binding is inhibited by serotonin (Ki = 48.5 microM), unlabeled ketanserin (Ki = 3-15 nM), as well as by another antiserotonergic drug, methysergide (Ki = 32.6 microM). However, other selective 5-HT2 ligands, such as ritanserin, spiperone and cyproheptadine fail to interact with 3H-ketanserin binding. On the contrary, tetrabenzine, a monoamine depleting agent, when preincubated at 30 degrees C, did inhibit the specific binding completely. 3H-ketanserin specific binding is inhibited in a dose-dependent fashion by some calcium blocking agents, with different potencies: verapamil (Ki = 2.25 microM), diltiazem (Ki = 139 microM) and SIM6080, a new Ca(2+)-antagonist related to the phenylalkylamines (Ki = 5.22 microM). Flunarizine inhibited 3H ketanserin specific binding only at relatively high concentrations (IC50 greater than 100 microM), while nitrendipine did not show any inhibitory effect up to 20 microM. The present evidence indicates that all the sites labeled by 3H ketanserin at 4 degrees C might be coincident with the monoamino transporter identified in other systems, and that they might play a role in the modulation of platelet aggregation exerted by some calcium blocking agents. PMID- 1409260 TI - Vigabatrin does not affect the intestinal absorption of phenytoin in rat duodeno jejunal loops in situ. AB - The antiepileptic drug vigabatrin (GVG) is known to decrease significantly the serum concentration of concurrently administered phenytoin (PHT) in epileptic patients. To assess a possible mechanism for this interaction, the effect of GVG on the intestinal absorption of PHT was investigated by means of circulation experiments in an in situ rat duodeno-jejunal loop. GVG did not affect the rate of disappearance of PHT from the loop perfusing medium, providing evidence against occurrence of GVG-induced impairment of PHT absorption. PMID- 1409261 TI - Introduction to immunopharmacology. PMID- 1409262 TI - Histocompatibility and clinical transplantation. PMID- 1409264 TI - Immunotherapy of cancer with interleukin-2 and lymphocytes (LAK or TIL). PMID- 1409263 TI - Combinations of biological response modifiers: rationale and clinical responses. PMID- 1409265 TI - Antagonistic effect of IL-2 on DTIC-induced impairment of tumor-specific cell mediated immunity in vitro. PMID- 1409266 TI - Immunomodulating therapy in autoimmune diseases. PMID- 1409267 TI - Immunotherapy of type I diabetes: rationale, results and prospects. PMID- 1409268 TI - Immunomodulating treatment in primary glomerulonephritides. PMID- 1409269 TI - Reliability of in vitro models for studies on immune functions by normal and immunomodulated phagocytes. PMID- 1409270 TI - Eicosanoids in allergic reactions: quantitative determination by enzyme immunoassay. PMID- 1409271 TI - Requirement of interleukin-1 beta, interleukin-6 and ICAM-1 for T cell activation by human hepatocellular carcinoma cells. PMID- 1409272 TI - Cyclosporin A and dipyridamole: an effective combination against the generation of cytotoxic T lymphocytes (CTL). PMID- 1409273 TI - Molecular weight-related antigenicity of peptides contained in cow's milk protein hydrolysates. PMID- 1409274 TI - Therapeutical effect of 4'-deoxy-4'-iododoxorubicin-loaded LAK cells in mice bearing lung metastases. PMID- 1409275 TI - In vitro activity of pharmacological compounds carried by lipidic microparticles. PMID- 1409276 TI - UN-1, a murine monoclonal antibody recognizing a human thymocyte undescribed antigen. AB - A monoclonal antibody (MoAb), UN-1, specific for a human thymocyte cell surface antigen was produced. The same MoAb recognized in immunofluorescence also cells of the human T line HPB-ALL, while did not bind human peripheral blood cells and cells of some T, B and myeloid lines. Western blotting analysis of thymocyte membranes with MoAb UN-1 revealed a structure with a molecular weight of 150 kDa. Therefore both the pattern of expression and the size of the antigen recognized by MoAb UN-1 did not correspond to any previously described cell surface molecule. PMID- 1409277 TI - Perspectives of measles, rubella and mumps eradication. PMID- 1409278 TI - Vaccines for the future. PMID- 1409279 TI - Analysis of the physical association between CD38 and functional molecules expressed by human lymphocytes. PMID- 1409280 TI - CD69 activation molecule: requirements for its expression on T cells. PMID- 1409281 TI - Activation of rat T cells in vitro and in vivo with a bispecific (anti-TCR x anti CD2) F(ab')2 derivative. PMID- 1409282 TI - Host-vs-graft and graft-vs-host reactivity and immune reconstitution after T depleted allogeneic bone marrow transplantation. PMID- 1409284 TI - Mode of interaction between a monoclonal antibody and human TNF alpha. PMID- 1409283 TI - Increase in the therapeutic effect of doxorubicin induced by monoclonal antibodies raised against this drug. PMID- 1409285 TI - Induction of anti-tumor immune response by bispecific monoclonal antibodies (bimAbs). PMID- 1409286 TI - Replacement therapy in hereditary and acquired angioedema. PMID- 1409287 TI - Role of TNF-alpha and therapeutic perspectives in bowel and myocardial ischemia/reperfusion injury. PMID- 1409288 TI - Lymphocytes-granulocytes interactions as model for the evaluation of immunomodulating drugs. PMID- 1409289 TI - Immunopharmacology of Pidotimod: effect on natural killer cell activity and thymocyte cell death. PMID- 1409290 TI - May children with recurrent respiratory infections be a test bed of immunomodulators? PMID- 1409292 TI - Influence of acute stress on function of polymorphonuclear leukocytes. PMID- 1409291 TI - Heart and heart-lung transplantation: the present situation. PMID- 1409293 TI - Protective effects of endotoxin tolerance in tumor bearing rats. PMID- 1409294 TI - Effects of beta-casomorphins and met-enkephalin on human natural killer activity. PMID- 1409295 TI - Nitric oxide (NO) mediates antidipsogenic action of Escherichia coli endotoxin (LPS) and tumor necrosis factor (TNF-alpha) in the rat. PMID- 1409296 TI - Evaluation of the kinetics of the immunomodulating activity of Pidotimod on human neutrophils. PMID- 1409297 TI - An HPLC method for the simultaneous analysis of urinary neopterin and kynurenine. PMID- 1409298 TI - Ex vivo evaluation of Pidotimod effect on immune response. PMID- 1409299 TI - The cyclosporin related toxicity in high risk liver transplant patients. PMID- 1409300 TI - FCM detection of lymphocytic beta-endorphin in cancer patients during hospitalization and after in vitro culture with IL2. PMID- 1409301 TI - Detection of lymphocytic beta-endorphin by flow cytometry. PMID- 1409302 TI - PMA-mediated inhibition of IL-2-driven differentiation of NK cell. PMID- 1409304 TI - Activity of the new immunostimulant PGT/1A against experimental bacterial infections. PMID- 1409303 TI - Immune recognition of drug-induced tumor antigens: a study with a nonimmunogenic, revertant clone. PMID- 1409305 TI - Inhibition of CTL-line lysis after gangliosides treatment. PMID- 1409306 TI - Structure-function analysis of human granulocyte-macrophage colony stimulating factor using synthetic peptides and antibodies. PMID- 1409307 TI - Impairment of cytolytic and proliferative responsiveness of peripheral blood mononuclear cells from cluster headache patients to IL-2. PMID- 1409308 TI - Effect of Pidotimod, a new immunostimulating agent, on some aspects of immune response. In vitro study. PMID- 1409309 TI - Evaluation of immunomodulating effects of inhaled bacterial polyribosomal Klebsiella pneumoniae proteoglycans complex on bronchoalveolar immune system in chronic bronchitis. PMID- 1409310 TI - Role of immune and/or natural factors of resistance of the host to tumor progression on the effectiveness of antitumor treatment. PMID- 1409311 TI - Immunoregulatory role of different T cell subsets in murine candidiasis. PMID- 1409312 TI - Effects of gamma interferon on a B16 melanoma cell line and its doxorubicin resistant variant. PMID- 1409313 TI - Molecular and genomic aspects of xenogenizing-alkylating drugs. PMID- 1409314 TI - Glucocorticoid-induced apoptosis of natural killer cells and cytotoxic T lymphocytes. PMID- 1409315 TI - Mechanism of the protective action of interleukin-1 in the experimental gastric damage in the rat. PMID- 1409316 TI - Genetic of drug induced immunopathologies. PMID- 1409317 TI - Interference of prolactin on some processes of nonspecific immunity. PMID- 1409318 TI - Effect of melatonin on the immune system. PMID- 1409319 TI - Role of 5-HT2 receptor subtypes in mediating adenosine-induced airway contraction. PMID- 1409320 TI - Neuropeptide-leukocyte interactions: examples of pharmacological modulation. PMID- 1409321 TI - Inhibition of eicosanoid formation and lipocortin induction by glucocorticoids in human cell lines and in patients with inflammatory lung disease. PMID- 1409322 TI - Specific immunotherapy: clinical efficacy and mechanisms of action. PMID- 1409323 TI - From exogenous cytokines to gene therapy: cytokine activated tumor inhibition. PMID- 1409324 TI - Glucocorticoid-induced DNA fragmentation: role of protein-kinase-C activity. AB - Glucocorticoid hormones (GCH) and IL-2 induce apoptotic cell death by a PKC dependent mechanism. IL-4 counteracts apoptosis by inhibiting PKC activity. GCH and IL-2 show antagonistic effects on apoptosis when administered together. These data indicate that PKC activation in response to different stimuli can both enhance or reduce thymocyte survival. PMID- 1409325 TI - Interleukin-2 and head and neck squamous cell carcinoma: clinical and pathological studies. PMID- 1409326 TI - Soluble and cell-associated IL-2 receptor (IL-2R) after local immunotherapy with recombinant interleukin-2 (rIL-2). PMID- 1409327 TI - Regional application of cytokines: experience with various clinical protocols. PMID- 1409328 TI - The thymic hormones in the treatment of immune deficiency related to HIV infection. PMID- 1409329 TI - Immune response to gp120 of HIV: antibody spectrotype and inhibitory activity on T cell functions. PMID- 1409330 TI - Comparative behavioural, pyrogenic and electrocortical effects of tumor necrosis factor-alpha and interleukin 1 beta in rat. PMID- 1409331 TI - O6-alkylguanine-DNA alkyltransferase activity in blasts obtained from patients with myelogenous or lymphocytic leukemia. PMID- 1409332 TI - Haemopoietic growth factors in oncology. PMID- 1409333 TI - Interleukin 2 in the management of hematologic malignancies. PMID- 1409334 TI - Secondary immunodeficiency in lymphoproliferative disorders. PMID- 1409335 TI - Secondary immunodeficiencies in surgical patients. PMID- 1409336 TI - Drug-induced immunodeficiencies. PMID- 1409337 TI - Immune-modulating drugs and infections in the elderly. PMID- 1409339 TI - ? + ? = creativity. PMID- 1409338 TI - Existence of a natural killer (NK) cell repertoire for (allo)antigen recognition: definition of five distinct NK-determined allospecificities in humans. PMID- 1409340 TI - The relationship of ideology to developing community health nursing theory. AB - Ideology plays a major role in developing theory, guiding education, and directing practice in nursing. This study investigated the opinions of community health nurse educators regarding specific elements of community health nursing ideology and its relationship to the educators' opinions about the appropriateness of existing theory for professional use. The majority of participants agreed that a specific set of beliefs can be called a community health nursing ideology. Covariant factor analysis indicated that it is not a undimensional, internally consistent single set of beliefs or values, but rather is a set of two types of values, one focusing on the individual and the other on society. Individually oriented beliefs were positively related to satisfaction with existing theory. Socially oriented beliefs were negatively related to satisfaction with existing theory, but the relationship was not statistically significant. Anyone engaged in developing community health nursing theory would do well to consider which ideologic model is undergirding the process. PMID- 1409341 TI - Toward redefining public health nursing in Canada: challenges for education. AB - Faced with a recent shift from a hospital-based to a community-based health care system, Canadian public health nurses are being challenged to redefine their roles. To empower these nurses to respond effectively, it is imperative that the profession be reclarified as a specialty with a distinct philosophy and mission. Nursing education is key to facilitate this process, and public health nursing educators must lead the way. Certain barriers hinder the response of public health nursing education, and four areas are suggested in which efforts to advance public health nursing may be best directed. PMID- 1409343 TI - Secondary data on health-related subjects: major sources, uses, and limitations. AB - Although secondary data are generally neglected by nurses, they are useful for nurse researchers, practitioners, educators, administrators, and policy makers. Major sources of data on health-related subjects are medical records, administrative records, the census, vital statistics, surveys of the National Center for Health Statistics, social science archives, and nursing archives, each with its specific uses and limitations. PMID- 1409342 TI - Health maintenance, health promotion: is there a difference? AB - Nurses in community settings are seeing more health care consumers who are medically stable and who are asking for assistance in areas such as exercise, stress reduction, nutrition, and illness and accident prevention. These requests can be characterized as concerns of health maintenance or health promotion. Two nursing diagnoses, altered health maintenance and health-seeking behaviors (specify), enable the practitioner to address these concerns in clinically useful ways. Through case studies and comparative tables, the differences between these two diagnoses is clarified to enable nurses to identify, treat, and evaluate efforts made to enhance health-oriented behaviors. PMID- 1409344 TI - Adaptation themes for prenatal care delivered by public health nurses. AB - An adaptation process involving three cognitive themes provides the framework for community nursing model for prenatal care on the island of Hawaii. The themes are based on the cognitive adaptation model developed by Taylor (1983) and include search for meaning, sense of mastery, and self-esteem. Each theme is used to guide public health nurses and is identified during designated encounters between the nurse and woman throughout the duration of prenatal care. A focus on adaptation themes for each trimester of pregnancy expands on the medical model of prenatal care to highlight developmental processes of childbearing and broaden the scope of practice for public health nurses responsible for assessment and intervention in the community. PMID- 1409345 TI - Maternal time and the care of disabled children. AB - Caring for disabled children has become increasingly the responsibility of parents, even when the medical care is complex. To assess the time commitment required, 133 mothers of disabled children were asked to estimate by specific task categories the extra time required to care for the children. Total average daily care time was reported at 12 hours and 6 minutes, with 6 hours and 30 minutes consumed in "vigilant" tasks (i.e., watching a child who cannot be left alone and/or providing emotional support). Multiple regression analysis showed an increase in total caregiving hours associated with a younger child who was more physically and mentally impaired, and who required more medical treatments. The amount of time required by parents to care for their chronically ill children of necessity results in lost opportunities. Because this burden is experienced primarily by women and because professional nurses could alleviate some of the burden, this issue deserves further study. PMID- 1409346 TI - Homelessness as a determinant of health. AB - The homeless population in the United States is variously estimated at between 350,000 and 2.5 million. Families and children are among the fastest-growing segments of this population. A combination of social and economic changes occurring nationally have contributed to this phenomenon. Conditions associated with homelessness have a profound effect on the individual's ability to maintain health, to have access to treatment, and to recuperate. Several health problems are specific to the homeless, and have implications for public health practitioners. PMID- 1409347 TI - Registered nurses' perceptions of their communication with Spanish-speaking migrant farmworkers in North Carolina: an exploratory study. AB - Communication forms the foundation for all that nurses do. Recently, nurses working with migrant farmworkers have become challenged as the language of this population has become predominantly Spanish. To explore how nurses in North Carolina are managing communication issues, 55 nurses at 12 state health care agencies that serve migrant farmworkers was surveyed. Data were collected to determine what nurses believed about various communication issues involving these Spanish-speaking clients, including how they were presently communicating with them, in what areas of nursing functions they believed communication barriers were problematic, what they were doing to improve their communication, and what they envisioned the potential solutions were concerning communication barriers. Language differences proved to be substantial barriers to adequate nursing care for these individuals. Nurses cited many problems and said that they were receiving little assistance from their agencies to improve direct communication with the clients. Responses indicated a need for and a willingness by nurses to focus on improving communication with Spanish-speaking clients. Classes held at their agencies were seen as the most effective way of learning Spanish. PMID- 1409348 TI - How elderly women cope: concerns and strategies. AB - Forty-two elderly women were asked to describe the problems they faced with aging, and how they coped with both real-life and hypothetical problems in seven areas. Content analysis indicated that their spontaneously reported ongoing strategies were consistent with current theoretical formulations, the strategies differed by area of concern and for real-life versus hypothetical problems, and direct action strategies were related to lower levels of psychologic distress. These results have implications for nursing research and practice. PMID- 1409349 TI - Approaching the media with confidence. AB - The media are useful in communicating health information to the public. They are also a powerful way to promote and maintain positive nursing images. This paper examines the past portrayals of nurses in the media, explores the benefits of communicating nursing knowledge to the profession and to the community, and suggests strategies to access the media. PMID- 1409350 TI - American Association of Pharmaceutical Scientists, 1992 annual meeting and exposition. San Antonio, Texas, November 15-19, 1992. Abstracts. PMID- 1409351 TI - Chemical stability of insulin. 1. Hydrolytic degradation during storage of pharmaceutical preparations. AB - Hydrolysis of insulin has been studied during storage of various preparations at different temperatures. Insulin deteriorates rapidly in acid solutions due to extensive deamidation at residue AsnA21. In neutral formulations deamidation takes place at residue AsnB3 at a substantially reduced rate under formation of a mixture of isoAsp and Asp derivatives. The rate of hydrolysis at B3 is independent of the strength of the preparation, and in most cases the species of insulin, but varies with storage temperature and formulation. Total transformation at B3 is considerably reduced when insulin is in the crystalline as compared to the amorphous or soluble state, indicating that formation of the rate-limiting cyclic imide decreases when the flexibility of the tertiary structure is reduced. Neutral solutions containing phenol showed reduced deamidation probably because of a stabilizing effect of phenol on the tertiary structure (alpha-helix formation) around the deamidating residue, resulting in a reduced probability for formation of the intermediate imide. The ratio of isoAsp/Asp derivative was independent of time and temperature, suggesting a pathway involving only intermediate imide formation, without any direct side chain hydrolysis. However, increasing formation of Asp relative to isoAsp derivative was observed with decreasing flexibility of the insulin three dimensional structure in the formulation. In certain crystalline suspensions a cleavage of the peptide bond A8-A9 was observed. Formation of this split product is species dependent: bovine greater than porcine greater than human insulin. The hydrolytic cleavage of the peptide backbone takes place only in preparations containing rhombohedral crystals in addition to free zinc ions. PMID- 1409352 TI - Chemical stability of insulin. 2. Formation of higher molecular weight transformation products during storage of pharmaceutical preparations. AB - Formation of covalent, higher molecular weight transformation (HMWT) products during storage of insulin preparations at 4-45 degrees C was studied by size exclusion chromatography. The main products are covalent insulin dimers (CID), but in protamine-containing preparations the concurrent formation of covalent insulin-protamine (CIP) products takes place. At temperatures greater than or equal to 25 degrees C parallel or consecutive formation of covalent oligo- and polymers can also be observed. Rate of HMWT is only slightly influenced by species of insulin but varies with composition and formulation, and for isophane (NPH) preparations, also with the strength of preparation. Temperature has a pronounced effect on CID, CIP, and, especially, covalent oligo- and polymer formation. The CIDs are apparently formed between molecules within the hexameric unit common for all types of preparations and rate of formation is generally faster in glycerol-containing preparations. Compared with insulin hydrolysis reactions (see the preceding paper), HMWT is one order of magnitude slower, except for NPH preparations. PMID- 1409353 TI - Derivatives of 4-(2-N,N-di-n-propylaminoethyl)-5-hydroxyindole: synthesis and pharmacological effects. AB - 5-Methoxy-1-methyl-4-(2-N,N-di-n-propylaminoethyl)indole (12) was synthesized from 5-hydroxyindole by a multistep synthesis. This target compound was designed as a bioisostere of "p-dimethoxy" catechol congeners of dopaminergic agonists derived from a variety of ring systems, in some of which p-dimethoxy-substituted systems are potent, active dopaminergic agonists. To complete the indole series, all possible combinations of N- and O-demethylated derivatives of 12 were prepared and were also evaluated pharmacologically. All members of this indole derived series showed a low order of cardiovascular activity, which appeared to be independent of dopamine receptors. The lack of dopaminergic activity of 12 is cited as yet another example of the unpredictable effect of replacement of the catechol moiety of a dopaminergic agonist with a p-dimethoxy moiety. PMID- 1409354 TI - Structural modification study of anthracyclinones: synthesis and biological activity of several derivatives of eta-pyrromycinone. AB - On the basis of the N-O-O triangular pharmacophore hypothesis postulated earlier in our laboratory, selected side chains with or without the nitrogen atom at the strategic position were incorporated to eta-pyrromycinone, one of the anthracyclinones derived from the antibiotic cinerubins. Since none of the anthracyclinones (the aglycones of anthracyclines) were reported to have antineoplastic activity, the validity of the proposed hypothesis could be tested. Results indicated that a compound designed in this manner, 1,4-bis[2-(2,2 dimethyloxazolidin-3-yl)ethylamino]-1,4-didehydr oxy-eta- pyrromycinone (9c) possessed both in vitro and in vivo antineoplastic activity comparable to that of mitoxantrone. The structure-activity relationship of this class of compounds is discussed. PMID- 1409355 TI - Improved delivery through biological membranes. XLV. Synthesis, physical-chemical evaluation, and brain uptake studies of 2-chloroethyl nitrosourea delivery systems. AB - The dihydropyridine in equilibrium with pyridinium redox chemical delivery system (CDS) was supplied to two 2-chloroethylnitrosoureas, i.e., HECNU and CCNUOH, and the physicochemical properties of the delivery systems were studied to assess their potential as improved delivery forms to the CNS. Detailed physicochemical evaluation and brain uptake studies were performed on one of the delivery systems (CCNUOH-CDS) derived from trans-4-hydroxy-CCNU, an active metabolite of CCNU. Two aqueous-based formulations derived from hydroxypropyl-beta-cyclodextrin (HP beta CD) and Tween 80:ethanol:water system were developed for CCNUOH-CDS to overcome the poor aqueous solubility conferred upon it by its high lipophilicity. The formulations enabled a 200- to 400-fold improvement in the water solubility of CCNUOH-CDS. Dose- and vehicle-dependent comparative tissue distribution studies in rats indicated improved brain-to-organ ratios of the delivery system at lower doses. PMID- 1409356 TI - Parenteral formulation of the kappa agonist analgesic, DuP 747, via micellar solubilization. AB - The nonopioid kappa agonist analgesic amine, DuP 747, as a hydrochloride salt exhibited an aqueous solubility of 3 mg/ml. This solubility was insufficient to provide the desired dose in a solution formulation for intramuscular administration. Aqueous solutions of the hydrochloride salt exerted surface activity behavior; however, the critical micellar concentration (CMC) was not reached at the saturation solubility. Enhanced aqueous solubility required to reach the CMC could lead to micellization of the compound and a possible i.m. solution formula. The methanesulfonate salt was more water soluble than the hydrochloride salt and yielded a micellar solution with a concentration of 60 mg/ml. PMID- 1409357 TI - Acceleration of heat transfer in vial freeze-drying of pharmaceuticals. II. A fluid cushion device. AB - A simple device for the improvement of freeze-drying efficiency is described. The device is an aluminum foil bag which contains a small amount of glycerin. The device can be either reusable or disposable. When placed on a freeze-drying tray the liquid is about 1 mm thick. When vials are placed on the device it conforms to the shape of the vial bottoms. Since both the aluminum foil and the glycerin are better heat conductors than a vacuum, the device improves heat transfer from the shelf to the vial. Drying times obtained with and without the device are compared for different sizes as well as different types of vials. In most cases the use of the device reduces the drying time by nearly a factor of two. The use of the device also increases vial-to-vial uniformity and minimizes the effect of spillage. PMID- 1409358 TI - Microencapsulation of solid dispersions: release of griseofulvin from griseofulvin:phospholipid coprecipitates in microspheres. AB - The preparation, characteristics, and behavior of microspheres of poly(L-lactic acid) (PLA) containing griseofulvin (Gris) or Gris:phospholipid coprecipitates are described. Microspheres were spherical and increased in size from 17 microns (empty) to 30 microns, containing 22% Gris. The release of coprecipitated Gris after 60 min from 146,000 MW PLA microspheres in pH 2.0 buffer at 37 degrees C was twofold greater than that from microspheres containing pure Gris. Also, the release profile from pure Gris microspheres was 25% lower than its dissolution profile, whereas the dissolution and microspheres of Gris coprecipitate suspended in PEG 600 in hard gelatin capsules for 1 week released Gris at levels comparable to the dissolution of coprecipitate. Decreasing the MW of PLA substantially increased the release of Gris from microspheres of coprecipitate after 20 min but insignificantly from microspheres of pure Gris. These findings suggest that microsphere formulation offers some new opportunities in the development of solid dispersions which normally encounter processing difficulties. PMID- 1409359 TI - The pharmacokinetics of pulmonary-delivered insulin: a comparison of intratracheal and aerosol administration to the rabbit. AB - The pulmonary deposition and pharmacokinetics of insulin, administered via an endotracheal tube as an aerosol and instillate, in formulations containing either 113mIn-DTPA or 99mTc-DTPA (for gamma scintigraphic imaging) have been studied in four male New Zealand White rabbits. Using a randomized crossover design, the pharmacokinetics of intravenous insulin were also characterized. Recovery of immunoreactive insulin after nebulization was greater than 90%, indicating that the aerosolisation procedure did not cause appreciable insulin degradation. Gamma scintigraphy demonstrated that the penetration index (peripheral:central deposition) for the aerosolized formulation (1.52) was much greater than that for the instillate (0.32). Gamma scintigraphy also allowed exact quantification of the dose deposited after aerosol administration and thus permitted accurate determination of bioavailabilities. The bioavailable fraction for aerosolized insulin was 10-fold greater than for instilled insulin (57.2 vs 5.6%). Mucociliary clearance was likely to be greater for the instillate since it showed a preferential central deposition; this may account for the lower bioavailability. Insulin pharmacokinetics from both pulmonary formulations were absorption rate limited, resulting in postpeak half-lives which were approximately 20-fold greater than the intravenous elimination half-life (3 min). The apparent absorption rate constants resulting from instillation and aerosolisation were statistically equivalent (0.015 and 0.011 min-1, respectively). Mucociliary clearance of insulin would result in an overestimation of the true absorption rate constant; hence if mucociliary transport were greater for the instillate, then the true airways to blood transfer rate constant will be higher for the aerosolized formulation. PMID- 1409360 TI - Immobilization of active urokinase on albumin microspheres: use of a chemical dehydrant and process monitoring. AB - A method of immobilizing urokinase on albumin microspheres has been developed. Laser scattering, which was used to follow particle size from the initial emulsification stage to the final aqueous resuspension of the microsphere stage, showed that particle coalescence and crosslinking were critical parameters in manufacturing the microspheres. Chemical dehydration with 2,2-dimethoxypropane was used to convert an albumin emulsion into an albumin suspension and to reduce coalescence. An optimal amount of dehydrant produced 0.3-micron particles which resisted a 50 degrees C temperature challenge. Since oil/glutaraldehyde emulsion resulted in large particles with no urokinase activity, the cross-linking concentration of glutaraldehyde was reduced by solubilizing 25% (w/v) glutaraldehyde in the oil phase with n-propanol. A concentration of 0.015% (v/v) glutaraldehyde effectively immobilized urokinase and stabilized albumin microspheres. Amidolytic activity using the specific chromogenic substrate for urokinase, S-2444, showed that enzyme activity could be retained during this glutaraldehyde cross-linking. PMID- 1409361 TI - Macrophage activation by polymeric nanoparticles of polyalkylcyanoacrylates: activity against intracellular Leishmania donovani associated with hydrogen peroxide production. AB - Nanoparticles of polyalkylcyanoacrylates (PACA) can be useful carrier for the targeting of antileishmanial drugs into macrophages and also possess significant antileishmanial activity by themselves. No significant difference in antileishmanial activity could be detected between nanoparticles of five PACAs with differing alkyl side chains, suggesting that the main degradation products of PACA are not involved in their antileishmanial action. The effect of polyisohexylcyanoacrylate (PIHCA) on the induction of the respiratory burst in a macrophage-like cell line (J774G8) was assessed in non-infected macrophages and in macrophages infected with amastigotes of Leishmania donovani infantum, by measuring nitroblue tetrazolium (NBT) reduction and hydrogen peroxide production. Phagocytosis of PIHCA nanoparticles led to a respiratory burst, which was more pronounced in infected than in uninfected macrophages. The production of reactive oxygen intermediates associated with the respiratory burst was inhibited by addition of superoxide dismutase and catalase to the cell suspensions. The addition of catalase to the culture medium together with PIHCA nanoparticles significantly reduced the antileishmanial activity of PIHCA. Moreover PIHCA nanoparticles did not induce interleukin-1 release by macrophages. It is suggested that the antileishmanial action of PIHCA and other PACA nanoparticles results from the activation of respiratory burst in macrophages. PMID- 1409362 TI - The mobile order theory versus UNIFAC and regular solution theory-derived models for predicting the solubility of solid substances. AB - The theory of mobile order of Huyskens is tested against the UNIFAC model, the regular solution model, and the extended Hildebrand or Hansen solubility approaches in predicting the solubility of naphthalene in both polar and nonpolar solvents at 40 degrees C. While all models correctly predict the solubility in nonpolar and moderately polar solvents, a substantial improvement is achieved by Huyskens' model, particularly in alcohols. This improvement originates from the correct description of the entropy effects as well as of the hydrophobic effects in the particular case of the alcohols. The model necessitates the knowledge of only one parameter not known a priori, i.e., the naphthalene modified nonspecific solubility parameter, the value of which is deduced from its solubility in hexane. PMID- 1409363 TI - Cholesterol (thermodynamic) activity determinations in bile salt-lecithin cholesterol systems and cholesterol-rich liquid crystalline mesophase formation. AB - Previous in vitro studies have shown that tauroursodeoxycholate (TUDC)-lecithin (L) micellar solutions solubilize cholesterol (Ch) poorly compared to its 7 alpha epimer, taurochenodeoxycholate (TCDC). However, in clinical studies ursodeoxycholic acid (UDC) has been found to be as effective as chenodeoxycholic acid (CDC) in Ch gallstone dissolution, and it has been suggested that, during UDC therapy, liquid crystalline mesophase formation may be involved in enhancing micellar Ch dissolution and dispersion. The purpose of the present study was to investigate whether measurements of the Ch thermodynamic activity (A(T) would provide new insights into the problem of Ch solubilization and mesophase formation in bile salt-lecithin-Ch systems. Using the silicone polymer uptake method developed in this laboratory, A(T) was measured as a function of Ch concentration in the TUDC-L-Ch and TCDC-L-Ch model bile systems. In the TCDC systems Henry's law was obeyed almost up to unit activity (i.e., A(T) was proportional to Ch concentration almost up to A(T) = 1.0). However, in many of the TUDC-containing systems negative deviations from Henry's law were observed well below unit activity and these systems became visibly turbid before saturation with respect to cholesterol monohydrate (ChM) was reached. The effects of varying the TCDC/TUDC ratio upon the A(T) behavior were also studied. With increasing TCDC/TUDC ratio, the onset of mesophase formation was shifted to higher A(T) values. A(T) measurements were also conducted in BS-L-Ch mixtures simulating biles of patients undergoing UDC therapy. The results obtained suggest that mesophase formation may not always occur in biles of patients undergoing UDC therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409364 TI - Plasma concentration clamping in the rat using a computer-controlled infusion pump. AB - We have developed a computer-controlled infusion pump to achieve rapidly and then maintain stable plasma thiopental concentrations in rats. Initially we derived the parameters of a triexponential pharmacokinetic model for thiopental, administered as a brief infusion to 10 rats, using nonlinear regression and standard pharmacokinetic equations. These parameters were incorporated into the pharmacokinetic model of a computer-controlled infusion pump. In a second group of animals this device was used to maintain three consecutive target thiopental concentrations ranging from 5 to 100 micrograms/ml in a stepwise fashion. Arterial blood gases were kept normal through controlled ventilation when necessary. The plasma thiopental concentrations in this second group of animals were generally higher than the target concentrations. The bias in pump performance (median prediction error) was +25%, and the inaccuracy (median absolute prediction error) was 26%. We fit the parameters of a three-compartment model to the plasma thiopental concentrations observed in the second group of animals. This produced a second set of thiopental pharmacokinetic parameters with the unique characteristic of having been derived from a computer controlled infusion study. These parameters were tested prospectively with a computer controlled infusion pump in a third group of animals. This second set of thiopental pharmacokinetic parameters performed better, with a median prediction error of 0% and a median absolute prediction error of 15%. This study shows that it is possible to achieve rapidly and maintain steady plasma thiopental concentrations in the rat. Our results suggest that it is feasible to derive robust pharmacokinetic parameters from unusual drug dosing approaches, such as employed by a computer-controlled infusion pump.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409365 TI - Stability of the new anticancer platinum analogue 1,2-diaminomethyl-cyclobutane platinum(II)-lactate (lobaplatin; D19466) in intravenous solutions. AB - The chemical stability of the new anticancer platinum analogue 1,2-diaminomethyl cyclobutane-platinum(II)-lactate (D19466) in infusion media was studied in an accelerated stability testing experiment with a selective HPLC-UV method. Variables were time, temperature, light, concentration, and infusion mixture. Mean reaction rate constants of decomposition were, respectively, 0.9555 *10(-2), 2.127 *10(-2), and 4.221 *10(-2) hr-1 at 37, 56, and 66 degrees C at a concentration of 200 mg/L in normal saline. From the Arrhenius equation, shelf lives (5% loss) at 4, 22, 37, and 121 degrees C were, respectively, calculated to be 41.6, 13.2, 5.7, and 0.15 hr. Mean reaction rate constant in 5% dextrose was 3.106 *10(-2) hr-1 (200 mg/L; 56 degrees C) and differed from that in normal saline (P less than 0.005). Mean reaction rate constant in Ringer lactate was 2.084 *10(-2) hr-1 (200 mg/L; 56 degrees C) (P greater than 0.05). There was no influence of normal daylight on the rate of decomposition. It is recommended to prepare D19466 infusions in normal saline. Chemical stability is then maximal 12 hr at room temperature or 24 hr at 4 degrees C. No protection against normal daylight is required. Sterilization by heat is not possible. PMID- 1409366 TI - Simultaneous microdetermination of rifampin, deacetylrifampin, isoniazid, and acetylisoniazid in plasma by liquid chromatography with dual electrochemical and spectrophotometric detection. AB - A rapid liquid chromatographic method for simultaneous determination of isoniazid (INH), acetylisoniazid (AINH), rifampin (RIF), and deacetylrifampin (DARIF) in microsamples of deproteinized plasma is described. The compounds and internal standard (IS) (diphenylcarbazide) were separated on a 10-microns, 8 mm x 10-cm phenyl Radial Pak cartridge in conjunction with a binary linear gradient system at a flow rate of 3 ml/min. A dual electrochemical (+800 mV) and spectrophotometric (334 nm) detection system with a computerized data station was employed to measure the above compounds in the effluent. Prior to injection, the plasma sample was diluted (2:1) with a pH 3, 0.075 M phosphate buffer after adding the internal standard (6.67 micrograms/ml of plasma) and passed through an Amicon Centrifree-MS filter at 2000g. Under these conditions, no interference in the analysis was observed, and the retention times of AINH, INH, IS, DARIF, and RIF were 3.95, 4.89, 15.82, 17.25, and 19.34 min, respectively. The linearity of the assay for all four compounds was excellent (r greater than 0.9925), and the between- and within-day CV was not greater than 8% at any concentration. This method is currently being used for therapeutic monitoring and pharmacokinetic studies of INH, RIF, and their major metabolites in patients with tuberculosis. PMID- 1409367 TI - Comparison of azone and hexamethylene lauramide in toxicologic effects and penetration enhancement of cimetidine in rabbit eyes. PMID- 1409368 TI - Pharmacokinetics of oral 2',3'-dideoxyinosine in rats. PMID- 1409369 TI - Opportunities for integration of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development. PMID- 1409370 TI - Pharmacodynamics of insulin following intravenous and enteral administrations of porcine-zinc insulin to rats. AB - Previous work from this laboratory showed site-dependent variations in the apparent permeability of insulin as measured using the everted rat gut sac technique, with the greatest permeability in the distal jejunum and the lowest in the duodenum (5). To quantify better the rate and extent of insulin absorption from the small intestine, closed-loop in situ experiments were performed in nondiabetic rats. Results correlated with the everted gut sac technique in that the absolute bioavailability determined in situ was higher for insulin solution administered to the more distal region of the intestine (0.133%) than that absorbed from an earlier portion of the intestine (0.059%). While the difference in regional bioavailabilities was not significant (P = 0.08), the blood glucose response showed highly significant differences (P = 0.0015), with severe and prolonged hypoglycemia resulting from insulin delivered to the distal jejunum/proximal ileum. Insulin administered iv followed a two-compartment pharmacokinetic model. Whole-body elimination rate constants were similar for both iv and enteral insulin. Although therapeutic quantities of insulin were absorbed from the distal small intestine, absorption enhancers would be necessary to decrease the dose of insulin required. PMID- 1409371 TI - Measurement of serum [3H]tetracycline kinetics and indices of kidney function facilitate study of the activity and toxic effects of bisphosphonates in bone resorption. AB - The [3H]tetracycline ([3H]TC) model is based on the observation that TC is released from the bones of rats prelabeled with [3H]TC via first-order kinetics, a factor directly reflecting the kinetics of bone resorption. In the present paper we applied the [3H]TC elimination model to rats treated with antiresorptive drugs. The validity of this model was evaluated by examining the effect of the bisphosphonate, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (ABP), and a novel bisphosphonate, dihydrogen disodium adipoylbisphosphonate (AdBP), on serum TC levels and the elimination rate constant. ABP and AdBP significantly inhibited the TC elimination rate. However, ABP treatment caused impairment of bone mineralization, renal dysfunction, and inhibition of somatic growth. It is concluded that antiresorptive effects of bisphosphonates could be evaluated by the [3H]TC model, but this model is limited to animals with normal kidney function. The experimental conditions provide a technically simple method which is sensitive enough to examine antiresorptive properties in a healthy animal and to detect adverse effects on the kidney. The activity of the novel bisacylphosphonate, AdBP, and lack of its adverse effects indicate the potential of this drug for clinical applications. PMID- 1409372 TI - Enhancement of nasal delivery of a renin inhibitor in the rat using emulsion formulations. AB - Nasal absorption of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L-leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (I), a renin inhibitor, was evaluated in two rat nasal models, one involving surgery and the other requiring no surgical intervention. Oleic acid/monoolein emulsion formulations were tested along with a control PEG 400 solution. The percent absolute bioavailability of the compound was enhanced from 3-6% (PEG 400 solution) to 15-27% when the emulsion formulations were used. The different nasal model techniques (with and without surgery) did not produce any statistical difference in the absolute bioavailability values for I. Emulsion formulations did not produce appreciable damage as assessed morphologically. It is suggested that emulsion formulations containing membrane adjuvants such as oleic acid and monoolein can be used to enhanced the nasal delivery of low-bioavailable, lipid soluble drugs. PMID- 1409374 TI - Quantitative evaluation of aqueous isopropanol enhancement of skin flux of terbutaline (sulfate). I. Ion associations and species equilibria in the formulation. AB - It has been reported previously that saturated terbutaline sulfate in aqueous isopropanol significantly enhances the terbutaline flux through human skin in vitro. This paper demonstrates that the effect of isopropanol on the permeant species in the formulation contributes to the flux enhancement. This demonstration is based on studies involving measurements of conductivity and pKa as well as NMR spectroscopy in isopropanol-water mixtures. Increasing isopropanol concentration inhibits the proton dissociation of terbutaline and results in the ion associations between the protonated terbutaline and its counterion, sulfate anion. The species present in the formulation include protonated terbutaline, the negatively charged terbutaline-sulfate (1:1) ion pair, and the neutral terbutaline-sulfate (2:1) ion triplet. The results of the studies provide the basis for a quantitative evaluation of the species equilibria in solutions of terbutaline sulfate. The saturated terbutaline sulfate in 60% isopropanol produces the maximum concentration of the neutral ion triplet. This result is almost parallel to the terbutaline skin flux, which maximized at 60-80% isopropanol. PMID- 1409373 TI - The transport barrier of epithelia: a comparative study on membrane permeability and charge selectivity in the rabbit. AB - The transport barrier of the epithelial presents one of the major problems limiting the effective use of these tissues as alternate delivery routes for macromolecules such as peptides and proteins. In the present study, two membrane transport properties, namely, the permeability and permselectivity of the shunt pathway, were investigated and compared in various tissues including the nasal, tracheal, bronchial, buccal, rectal, vaginal, corneal, epidermal, duodenal, jejunal, ileal, and colonic epithelia. Membrane permeability was evaluated using a combined method based on electrical conductance and flux measurements of a hydrophilic fluorescent probe, 6-carboxy fluorescein (CF). Membrane permselectivity or the charge discriminating ability of the membrane was evaluated by KCl diffusion potential measurements. The results indicate that all epithelia under investigation possess a relatively high degree of permeation barrier and are highly selective for the absorption of positively charged solutes. Shunt path permeability was found to vary greatly among tissues from different epithelia, whereas membrane charge selectivity was relatively constant in these tissues. A good correlation was observed between membrane electrical conductance and steady-state flux of CF, indicating a paracellular transport of the compound. The rank order of the intrinsic membrane permeability was as follows: intestinal approximately nasal greater than or equal to bronchial greater than or equal to tracheal greater than vaginal greater than or equal to rectal greater than corneal greater than buccal greater than skin. Membrane permselectivity, expressed as the ratio of transport number (positive over negative), ranges from 1.78 for the buccal to 1.33 for the rectal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409375 TI - Sonophoresis. II. Examination of the mechanism(s) of ultrasound-enhanced transdermal drug delivery. AB - We have shown previously that high-frequency ultrasound (sonophoresis) can significantly enhance the transdermal delivery of a topically applied drug in vivo and that the augmentation of transport was caused by the action of the ultrasound on the skin. However, these earlier experiments did not reveal (i) the mechanism of sonophoresis, (ii) the pathway of drug permeation under the influence of ultrasound, and (iii) any potentially detrimental effects of the enhancement procedure on skin structure and morphology. In the study reported here, these three key issues have been addressed using electron microscopy to follow the penetration of an electron-dense, colloidal tracer (lanthanum hydroxide; LH). Experiments have again been performed using the hairless guinea pig animal model. Colloidal LH suspensions were applied to skin sites, which were then immediately exposed to ultrasound (at 10 or 16 MHz) for 5 or 20 min. Passive transport of LH under identical conditions (but without ultrasound) provided the control measurements. Tissue processing after the treatment periods utilized standard electron microscopy staining procedures. We found the following: (1) LH does not permeate the skin by passive diffusion; under the influence of ultrasound, on the other hand, it penetrates through the stratum corneum (SC) and the underlying viable epidermal cell layers via an apparently intercellular route. (2) LH transports through the epidermis to the upper dermis, even after only 5 min of ultrasound treatment, a remarkable and unexpected finding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409376 TI - Brain parenchymal metabolism of 5-iodo-2'-deoxyuridine and 5'-ester prodrugs. AB - In an attempt to generate derivatives of 5-iodo-2'-deoxyuridine (IDU) with enhanced blood-brain barrier (BBB) permeability, a series of 5' ester prodrugs of IDU was synthesized and their metabolism studied in rat brain homogenate and its different subcellular fractions. The rate of hydrolysis was dependent on the steric and polar nature of the ester substituent. Ester hydrolyzing activities were associated primarily with the cytosolic fraction and were due mainly to the presence of cholinesterases as confirmed by inhibition experiments performed with different esterase inhibitors. The metabolism of IDU to 5-iodouracil (5-IU) by the cytosolic fraction, in the presence and absence of specific pyrimidine nucleoside phosphorylase inhibitors, also suggests that there are two specific enzyme systems catalyzing two different metabolic processes. IDU 5'-esters competitively inhibit the metabolism of IDU and the inhibitory effect depends on the affinity of a particular ester toward the enzyme and also on the rate by which the ester itself undergoes hydrolysis. In the absence of any 5'-ester, 95% IDU was metabolized within 6 hr. However, in the presence of an eightfold molar excess of butyryl-IDU, the hydrolysis of IDU was completely inhibited over a 6-hr time period. PMID- 1409377 TI - Disposition, bioavailability, and serum protein binding of pentachlorophenol in the B6C3F1 mouse. AB - The toxicokinetics of pentachlorophenol (PCP) were studied in B6C3F1 mice, a strain in which PCP was previously found to be carcinogenic. In a crossover design, doses of 15 mg/kg were given intravenously (bolus) and orally (gastric intubation) to six animals. Concentrations of PCP in blood, urine, and feces were measured by capillary gas chromatography with electron-capture detection. After intravenous administration, the values of clearance and volume of distribution were 0.057 +/- 0.007 L/hr/kg and 0.43 +/- 0.06 L/kg, respectively. These two parameters exhibited low intermouse variability (coefficients of variation less than 14%). The elimination half-life was 5.2 +/- 0.6 hr. After oral administration, the PCP peak plasma concentration (28 +/- 7 micrograms/ml) occurred at 1.5 +/- 0.5 hr and absorption was complete (bioavailability = 1.06 +/ 0.09). The elimination half-life was 5.8 +/- 0.6 hr. Only 8% of the PCP dose was excreted unchanged by the kidney. PCP was primarily recovered in urine as conjugates. A portion of the dose was recovered in urine as the mutagen, tetrachlorohydroquinone (5%) (TCHQ), and its conjugates (15%). For both PCP and TCHQ, sulfates accounted for 90% or more of the total conjugates (glucuronides and sulfates). PMID- 1409378 TI - Pharmacokinetic analysis of the structural requirements for forming "stable" analogues of valpromide. AB - The following valpromide (VPD) analogues were synthesized and their structure pharmacokinetic relationships explored: 3-ethyl pentanamide (EPD), methylneopentylacetamide (MND), 1-methyl cyclohexanecarboxamide (MCD), cycloheptanecarboxamide (CHD), and t-butylacetamide (TBD). Two aliphatic (EPD and MND) and two cyclic amides (MCD and CHD) underwent complete or partial conversion to their corresponding acids. The only amide found in this study to be "stable" to the amide-acid biotransformation was TBD. It also had the lowest clearance and the longest half-life and mean residence time. Unlike the other investigated amides, TBD contained two substitutions of two methyl moieties at the beta position of its chemical structure. A "stable" valpromide analogue must have either two substitutions at the beta position, such as in the case of TBD, or a substitution in the alpha and beta positions, such as in the case of the VPD isomer valnoctamide (VCD). This paper discusses the antiepileptic potential of stable VPD analogues which may be more potent and less teratogenic than their biotransformed isomers. PMID- 1409379 TI - Pilocarpine disposition and salivary flow responses following intravenous administration to dogs. AB - Oral doses of pilocarpine increase salivary flow rates in patients afflicted with xerostomia (dry mouth). This study examined the pharmacokinetics of and a pharmacodynamic response (salivation) to intravenous pilocarpine nitrate administration in dogs. Disposition was linear over a dose range of 225-600 micrograms/kg; plasma concentrations were 10-120 micrograms/L. Elimination was rapid and generally biphasic, with a terminal elimination half-life of approximately 1.3 hr. The systemic clearance of pilocarpine was high (2.22 +/- 0.49 L/kg/hr) and its steady-state volume of distribution (2.30 +/- 0.64 L/kg) was comparable to that of many other basic drugs. All doses of pilocarpine induced measurable submaxillary and parotid salivary flow rates which could be maintained constant over time. Cumulative submaxillary saliva flow was linearly related to total pilocarpine dose. Plasma pilocarpine concentration was linearly related to both steady-state and postinfusion submaxillary salivary flow rates. PMID- 1409380 TI - Nonlinear disposition of intravenous 2',3'-dideoxyinosine in rats. AB - The pharmacokinetics of 2',3'-dideoxyinosine (ddI) were examined in rats given intravenous doses of 8, 40, or 200 mg/kg. The concentrations of ddI in whole blood and plasma were identical. The concentration decline was multiexponential, with mean half-lives of 2 and 20 min for the first and second phases, respectively. At the highest dose, a slower third phase with a half-life of 56 min was observed. The total-body clearances were 99, 77, and 37 ml/min-kg for the 8, 40, and 200 mg/kg doses. The steady-state volume of distribution showed a trend for a decrease with increasing doses, but the difference was not statistically significant. Twenty-four-hour urinary recovery of unchanged drug for the three doses was similar at about 20%, suggesting that a major fraction of the dose was metabolized. Urinary excretion of ddI metabolite, hypoxanthine, accounted for less than 5% of the dose. Renal and metabolic clearances decreased with increased doses. ddI was metabolized in blood; the addition of inorganic phosphate, a cosubstrate in phosphorylase-mediated nucleoside catabolism, enhanced the degradation by about fourfold. In summary, these data indicate equal distribution of ddI in the extracellular and intracellular spaces in blood, its enzymatic degradation in blood, and nonlinear elimination kinetics. PMID- 1409381 TI - Is ICRF-187 [(+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane] unusually reactive for an imide? AB - The hydrolysis of ICRF-187 and two model compounds, 4-methylpiperazine-2,6-dione (4-MP) and 3-methylglutarimide (3-MG), was investigated over the neutral to alkaline pH range at 25 degrees C and an ionic strength of 0.5 (sodium chloride). The purpose of the study was to correlate the influence of molecular changes to the reactivity of these imides. Additionally, an improved chromatographic resolution of all the components of the degradation and NMR confirmation of the identity of the degradation products are presented. Based on the study of 4-MP, which is essentially half of an ICRF-187 molecule, and 3-MG, which has a carbon in place of the piperazine nitrogen, several conclusions can be drawn with regard to the stability of ICRF-187. The tertiary piperazine nitrogen/s of 4-MP and ICRF 187 contributed to the base-catalyzed hydrolysis of these compounds above pH 7 and caused a significant decrease in the pKa values of the imide moiety of ICRF 187 and 4-MP compared with 3-MG. One 2,6-piperazinedione ring of ICRF-187 was shown to affect only minimally the rate of hydrolysis of the second ring. ICRF 187 hydrolyzes by parallel consecutive pathways forming two monoacids with one ring opened and, subsequently, the diacid with both rings hydrolyzed. PMID- 1409382 TI - Formation of the racemic compound of ephedrine base from a physical mixture of its enantiomers in the solid, liquid, solution, or vapor state. AB - Physical mixtures (conglomerates) of the two enantiomers of ephedrine base, each containing 0.5% (w/w) of water, were observed to be converted to the 1:1 racemic compound in the solid, liquid, solution, or vapor state. From a geometrically mixed racemic conglomerate of particle size 250-300 microns (50-60 mesh), the formation of the racemic compound follows second-order kinetics (first order with respect to each enantiomer), with a rate constant of 392 mol-1 hr-1 at 22 degrees C. The reaction appears to proceed via the vapor phase as indicated by the growth of the crystals of the racemic compound between diametrically separated crystals of the two enantiomers in a glass petri dish. The observed kinetics of conversion in the solid state are explained by a homogeneous reaction model via the vapor and/or liquid states. Formation of the racemic compound from the crystals of ephedrine enantiomers in the solution state may explain why Schmidt et al. (Pharm. Res. 5:391-395, 1988) observed a consistently lower aqueous solubility of the mixture than of the pure enantiomers. The solid phase in equilibrium with the solution at the end of the experiment was found to be the racemic compound, whose melting point and heat of fusion are higher than those of the enantiomers. An association reaction, of measurable rate, between the opposite enantiomers in a binary mixture in the solid, liquid, solution, or vapor state to form the racemic compound may be more common than is generally realized. PMID- 1409384 TI - Corticosteroid pharmacodynamic modeling: osteocalcin suppression by prednisolone. PMID- 1409383 TI - Aqueous stability and solubility of CI-988, a novel "dipeptoid" cholecystokinin-B receptor antagonist. AB - The aqueous solubility and solution stability of the N-methylglucamine and sodium salts of CI-988 (CI-988 NMG and CI-988 Na) were evaluated to aid in the development of a parenteral formulation for preclinical and clinical testing. CI 988 ([R-(R*,R*)]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2- [[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)- carbonyl]amino]propyl]amino]-1 phenylethyl]amino]-4-oxobutanoic acid) is a selective "dipeptoid" cholecystokinin B receptor antagonist. The shape of the pH-solubility profile, generated at 30 degrees C, is consistent with the ionization of the terminal carboxyl group (pKa of 4.34). The pH-rate profile is independent of the salt form and is well described by two reaction pathways: spontaneous or water-catalyzed degradation of the nonionized form and specific base-catalyzed catalyzed degradation of the ionized form. The primary mechanism of degradation from the former pathway is consistent with intramolecular, carboxyl-assisted, amide-bond cleavage, whereas the primary mechanism of degradation from the latter pathway appears to be intramolecular cyclization to a hydantoin product with expulsion of 2 adamantanol. The pH dependencies of the solubility and stability show that a simple aqueous buffered solution of CI-988 has a predicted t90 of 2.1 years and a solubility of 0.94 mg/ml at pH 6.5, the theoretical pH of maximum stability, and 30 degrees C. PMID- 1409385 TI - Inhibition of hepatic and cutaneous biotransformation of resorufin ethers following intraperitoneal administration of 1-aminobenzotriazole. PMID- 1409386 TI - Peptides are better absorbed from the lung than the gut in the rat. PMID- 1409388 TI - Protein-peptide interactions as probed by tryptophan fluorescence: serum albumins and enkephalin metabolites. AB - Binding of Leu-enkephalin and the enkephalin metabolite, tyrosine-glycine-glycine (TGG), to bovine serum albumin (BSA) was studied as a model to investigate protein peptide interactions. TGG and Leu-enkephalin quench the tryptophyl fluorescence of BSA. Stern-Volmer quenching constants were typically in the range of 40 to 300 M-1, depending on the experimental conditions. The addition of Cu(II) or Ni(II) did not change the quenching constant, indicating that TGG does not compete for the metal binding sites on BSA. From fluorescence quenching studies with TGG, tyrosyl-glycine, tyrosine and glycyl-glycine, it was concluded that the presence of the tyrosine residue is required for the observed quenching. The phenolic group in tyrosine accounted for the quenching mechanism because phenol was efficient in quenching BSA fluorescence, whereas phenylalanine had no detectable effect. A large solvent isotope effect on the quenching constant of phenol and TGG with BSA strongly suggests an active role of the -OH functionality in the quenching mechanism. PMID- 1409389 TI - An implantable dosage form for the treatment of bone infections. AB - The object of this investigation was the development of an implantable sustained release dosage form, for the treatment of bone infections. Cross-linked polydimethylsiloxane (PDMS) was used as the matrix material. The drug delivery system was prepared by incorporating tobramycin, as a free base (C18H37N5O9.H2O) or as a sulfate salt [(C18H37N5O9)2.5H2SO4], into the matrix and molding into spherical beads. Following in vitro studies, the cumulative amount of drug released when plotted as a function of the square root of time was linear for both the base and the salt. The addition of glycerol to the matrix substantially accelerated the rate of drug release and the plots of cumulative amount of drug released continued to be linear as a function of the square root of time. The glycerol-incorporated beads swelled in contact with the aqueous medium but a negligible amount of glycerol was released even after exposure to the medium for 20 days. 13C solid-state and high-resolution NMR studies indicated that a fraction of the added glycerol participated in the cross-linking reaction of the polymer. The effect of the initial molecular weight of PDMS and the effect of the concentration of the cross-linker on the kinetics of drug release were investigated. PMID- 1409390 TI - Transport of thyrotropin releasing hormone in rabbit buccal mucosa in vitro. AB - The transport of thyrotropin releasing hormone (TRH) in rabbit buccal mucosa in vitro has been investigated with respect to (a) rate and type of metabolism of TRH on mucosal and serosal sides of buccal mucosa, (b) mechanism of TRH transport including charge effect on its permeability, and (c) pathway and rate-limiting regions of TRH movement. In addition, the integrity of excised buccal mucosa has been evaluated for purposes of in vitro solute diffusion experiments using tissue ATP level data, transmission electron microscopy, and TRH transport kinetic data. The results indicate that excised rabbit buccal mucosa can be used for TRH diffusion studies for approximately 6 hr. In addition, TRH apparently traverses buccal mucosa by simple diffusion with a steady-state permeability of about 10( 7) cm/sec, and this permeability is independent of pH. Moreover, the primary pathway appears to be via the intercellular space in the rate-limiting barrier, i.e., the upper 50 microns of the epithelium. Finally, TRH is degraded predominantly by deamidase activity, which is followed by, to a lesser degree, carboxypeptidase metabolism. PMID- 1409387 TI - Structural specificity of mucosal-cell transport and metabolism of peptide drugs: implication for oral peptide drug delivery. AB - The brush border membrane of intestinal mucosal cells contains a peptide carrier system with rather broad substrate specificity and various endo- and exopeptidase activities. Small peptide (di-/tripeptide)-type drugs with or without an N terminal alpha-amino group, including beta-lactam antibiotics and angiotensin converting enzyme (ACE) inhibitors, are transported by the peptide transporter. Polypeptide drugs are hydrolyzed by brush border membrane proteolytic enzymes to di-/tripeptides and amino acids. Therefore, while the intestinal brush border membrane has a carrier system facilitating the absorption of di-/tripeptide drugs, it is a major barrier limiting oral availability of polypeptide drugs. In this paper, the specificity of peptide transport and metabolism in the intestinal brush border membrane is reviewed. PMID- 1409391 TI - Assessment of the twin impinger for size measurement of metered-dose inhaler sprays. AB - The calibration of the first stage of the twin-stage impinger, an instrument proposed for use in measuring the spray size from metered-dose inhalers, was performed with monodisperse aerosols by a standard technique for cascade impactors. The mean cut point was found to be not particularly sensitive to operating variables which may be expected to occur in practice. The cut point was close to that reported previously, although the collection efficiency curve was found to be slightly sharper. Calculations are reported on the expected results of measurements on aerosols in a two-stage instrument with an idealized perfect collection efficiency curve as well as the curve measured for the twin impinger. These results indicate that important characteristics of spray size distribution cannot be distinguished with an ideal two-stage instrument; the twin impinger is less capable than an ideal instrument. PMID- 1409392 TI - Calcium alginate beads as core carriers of 5-aminosalicylic acid. AB - The utilization of calcium alginate beads as core carriers for delayed dissolution followed by burst release as a potential method of intestinal site specific drug delivery was investigated. 5-Aminosalicylic acid was spray-coated on dried calcium alginate beads and then coated with different percentages of enteric coating polymer and/or sustained-release polymer. Beads coated with more than 6% (w/w) methacrylic copolymer plastisized with dibutyl sebacate and triethyl citrate resisted release in 2-hr acid fluid challenge and allowed immediate dissolution upon transfer to simulated intestinal fluid. With 6% (w/w) methacrylic copolymer on top of 4% (w/w) ethylcellulose polymer, the major portion of drug did not release in 2 hr of acid treatment or the next 3 hr of simulated intestinal fluid treatment. This dosage form provides the possibility to deliver drug to the lower intestinal tract with minimal early release, followed by sustained release in the colon. PMID- 1409393 TI - Indomethacin-loaded microspheres: design and preparation by a multiple emulsification technique and their in vitro evaluation. AB - A new oral controlled-release drug delivery system was developed with two polymers using a multiple-emulsification technique. Powdered drug was dispersed in methyl cellulose sol, which was emulsified in ethyl cellulose solution in ethyl acetate. The primary emulsion thus formed was reemulsified in aqueous medium. During this phase, discrete microspheres were formed under optimized conditions. The size distribution of the microspheres was investigated, and scanning electron microscopy revealed the surface topography of the microspheres. The in vitro drug release followed first-order diffusion-controlled dissolution. More than 85% of the drug was released over 6 hr at pH 6.2 for all dissolution batches. PMID- 1409394 TI - Evaluation of mucoadhesive polymers in ocular drug delivery. II. Polymer-coated vesicles. AB - Association of Carbopol 934P and Carbopol 1342 (a hydrophobic modified Carbopol resin) with phospholipid vesicles was assessed by photon correlation spectroscopy and microelectrophoresis at pH 7.4 and 5. The precorneal clearance of the polymer coated vesicles was compared to that of uncoated vesicles by lacrimal dacryoscintigraphy in the rabbit. The mucoadhesive polymer-coated vesicles demonstrated significantly enhanced precorneal retention compared to noncoated vesicles only at pH 5 (P less than 0.005). The entrapment and subsequent release of tropicamide from Carbopol 1342-coated and uncoated liposomes were determined in vitro together with an in vivo evaluation of the vesicles formulated at the lower pH. Mucoadhesive polymer-coated vesicles failed to increase significantly the bioavailability of the entrapped tropicamide compared to uncoated vesicles and aqueous solution. PMID- 1409395 TI - Percutaneous absorption and metabolism of lonapalene in psoriatic skin. AB - The percutaneous absorption and metabolism of lonapalene (6-chloro-2,3 dimethoxynaphthalene-1,4-diol-diacetate; RS-43179), a topically effective 5 lipoxygenase inhibitor, has been measured in six subjects with stable plaque-type psoriasis of the lower extremities. Lonapalene readily penetrates psoriatic skin, is rapidly and completely metabolized, and is almost entirely excreted in the urine. Unexpectedly we observed a trend for thigh (T) plaque skin to be more permeable than lower leg (LL) plaque skin as measured by total absorption (T, 44.8 +/- 13.4%; LL, 24.9 +/- 12.6% applied dose excreted), peak plasma levels (T, 209 +/- 107; LL, 146 +/- 81 ng Eq/ml), and peak rate of urinary excretion (T, 591.7 +/- 112.2; LL, 318.4 +/- 143.9 micrograms Eq/hr). There were also differences in the metabolic profiles between the two sites as measured by the quantity and proportion of dealkylated and conjugated products excreted in the urine. PMID- 1409396 TI - Correlation between the inhibitory effects of basic drugs on the uptake of cardiac glycosides and taurocholate by isolated rat hepatocytes. AB - The role of the multispecific bile acid transporter for cardiac glycoside uptake is still controversial. This study was designed to examine the inhibitory effects of basic drugs (verapamil, dipyridamole, nifedipine, chlorpromazine, disopyramide, quinidine, propranolol, and lidocaine) on taurocholate uptake by isolated rat hepatocytes and to compare these effects with inhibition of ouabain uptake. Sodium-dependent taurocholate uptake was significantly reduced, to 50-70% of the control value, by 50 microM verapamil, dipyridamole, and nifedipine. Sodium-independent taurocholate uptake was more extensively inhibited, to 20-40%, by these basic drugs. The inhibition of ouabain uptake correlated better with sodium-independent taurocholate uptake (gamma = 0.918) than with sodium-dependent taurocholate uptake (gamma = 0.714). Taurocholate competitively inhibited ouabain uptake in the absence of sodium. These results indicate that the cardiac glycoside transport system is similar to the sodium-independent taurocholate transport system. PMID- 1409398 TI - In vivo percutaneous absorption of hydrocortisone: multiple-application dosing in man. AB - Percutaneous absorption of hydrocortisone was measured in six healthy adult men from whom informed consent had been obtained. The study compared a single topical dose to multiple-topical dose treatments (one vs three applications) on the same day. 14C-Labeled hydrocortisone in acetone was applied to 2.5 cm2 of ventral forearm skin and protected with a nonocclusive polypropylene chamber. The amount of 14C measured in urine collected over 7 days was used to determine hydrocortisone absorption. The treatments, performed 2 to 3 weeks apart, each utilized adjacent sites on the same individuals. A single dose of 13.33 micrograms/cm2 delivered 0.056 microgram/cm2 of hydrocortisone through the skin. When the single dose was tripled to 40 micrograms/cm2, the amount delivered through the skin increased by nearly three times, from 0.056 to 0.140 micrograms/cm2; the expected delivery was 3 x 0.056 micrograms/cm2 = 0.168 microgram/cm2. Three serial doses of 13.33 micrograms/cm2 (total, 40 micrograms/cm2) were also expected to deliver 0.168 micrograms/cm2 with or without soap and water washing between doses, but the observed amount of hydrocortisone delivered through the skin significantly exceeded our expectations. This indicates that multiple-dosing treatments resulted in a significant increase in bioavailability. It is postulated that increased vehicle application and washing dissolved and mobilized previously dosed hydrocortisone and increased bioavailability. PMID- 1409397 TI - Cyclodextrins as nasal absorption promoters of insulin: mechanistic evaluations. AB - The safety and effectiveness of cyclodextrins (CD) as nasal absorption promoters of peptide-like macromolecules have been investigated. The relative effectiveness of the cyclodextrins in enhancing insulin nasal absorption was found to be in the descending order of dimethyl-beta-cyclodextrin (DM beta CD) greater than alpha cyclodextrin (alpha-CD) greater than beta-cyclodextrin (beta-CD), hydroxypropyl beta-cyclodextrin (HP beta CD) greater than gamma-cyclodextrin (gamma-CD). A direct relationship linking absorption promotion to nasal membrane protein release is evident, which in turn correlates well with nasal membrane phospholipid release. The magnitude of the membrane damaging effects determined by the membrane protein or phospholipid release may provide an accurate, simple, and useful marker for predicting safety of the absorption enhancers. In order to estimate further the magnitude of damage and specificity of cyclodextrin derivatives in solubilizing nasal membrane components, the enzymatic activities of membrane-bound 5'-nucleotidase (5'-ND) and intracellular lactate dehydrogenase (LDH) in the perfusates were also measured. HP beta CD at a 5% concentration was found to result in only minimal removal of epithelial membrane proteins as evidenced by a slight increase in 5'-ND and total absence of LDH activity. On the other hand, 5% DM beta CD caused extensive removal of the membrane-bound 5'-ND. Moreover, intracellular LDH activity in the perfusate increased almost linearly with time. The cyclodextrins are also capable of dissociating insulin hexamers into smaller aggregates, and this dissociation depends on cyclodextrin structure and concentration. Enhancement of insulin diffusivity across nasal membrane through dissociation may provide an additional mechanism for cyclodextrin promotion of nasal insulin absorption. PMID- 1409399 TI - Effects of transdermal penetration enhancers on the permeability of shed snakeskin. AB - The effects of Azone and lauryl alcohol on the permeability of shed snakeskin were examined. Permeability of a variety of compounds through shed snakeskin was increased after Azone or lauryl alcohol pretreatment but the magnitude of the enhancement varied depending on the lipophilicity and the molecular size of the permeant. It was found that the shed snakeskin became more permeable after Azone or lauryl alcohol pretreatment, with a greater permeability increase for more hydrophilic and larger-molecular size permeants. As has been shown for untreated shed snakeskins, both the lipophilicity and the molecular size of the permeants are important in skin penetration and in determining the effects of transdermal penetration enhancers. PMID- 1409400 TI - Enhanced delivery of 5-iodo-2'-deoxyuridine to the brain parenchyma. AB - 5'-Ester derivatives of 5-iodo-2'-deoxyuridine (IDU) with varying degrees of lipophilicity were examined to evaluate the effectiveness of lipophilic ester prodrugs for enhanced and sustained delivery of IDU to the brain parenchyma. Approximately 1.0% (1.0 +/- 0.19; n = 4) of the total radioactivity was found in the brain at 30 min following intravenous administration of the lipophilic benzoyl-5'-ester of 125I-labeled IDU, whereas IDU per se yielded only 0.01% (0.01 +/- 0.06; n = 4). Since the IDU 5'-esters generated significantly higher levels of IDU in the brain, an HPLC analysis of IDU in the presence of 5'-esters and the metabolite 5-iodouracil was developed to characterize IDU uptake in the brain. The drug was detected at levels of 6.6 and 9.5 micrograms/g of brain tissue at 3 hr following intravenous administration of valeryl and benzoyl IDU, respectively, at a dose level of 40 mg/kg IDU equivalent each. IDU, on the other hand, when injected at a similar dose level, produced concentration levels below 0.01 micrograms/g of brain tissue, which was too low to be detected accurately by the HPLC assay. These results suggest that the 5'-ester derivatives cross the blood brain barrier effectively and generate significantly higher brain levels of the parent drug in the brain parenchyma. The regenerated hydrophilic drug because of its polarity is "locked in" the brain and is subsequently metabolized by pyrimidine phosphorylase to 5-iodouracil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409401 TI - Direct suppression of phagocytosis by amphipathic polymeric surfactants. AB - Recent studies have demonstrated that phagocytosis of colloidal particles by the mononuclear phagocytes of the liver and spleen can be controlled by either coating or stabilizing particulate carriers with the amphipathic polymeric surfactants, F108 and T908. These surfactants consist of copolymers of polypropylene oxide (PPO) and polyethylene oxide (PEO) and, when adsorbed to particulate surfaces, significantly decrease sequestration of particulates by the mononuclear phagocytes (MPS) of the liver. To evaluate these observations further, murine peritoneal macrophages were incubated for varying periods with surfactant-coated and noncoated polystyrene particles (PSPs). Phagocytosis was monitored using gamma counting and quantitative fluorescence microscopy. The data show that phagocytosis is decreased when PSPs are coated with F108 and T908. In addition, suppression of phagocytic activity was observed when cells were pretreated with the surfactant and then challenged with noncoated particles. The data confirm previous observations that polymeric surfactants consisting of PEO and PPO protect particulate carriers from rapid uptake by the MPS of the liver. Further, F108 and T908 suppress phagocytosis directly without affecting the integrity, viability, or functional state of the cell. PMID- 1409402 TI - Nasal membrane and intracellular protein and enzyme release by bile salts and bile salt-fatty acid mixed micelles: correlation with facilitated drug transport. AB - The effects of four bile salts, one fusidate derivative, and one mixed micellar formulation of bile salt-fatty acid combination on the nasal mucosal protein and enzyme release have been investigated in rats using an in situ nasal perfusion technique. Deoxycholate (NaDC) was found to possess the maximum protein solubilizing activity, followed by taurodihydrofusidate (STDHF), cholate, glycocholate (NaGC), and taurocholate (NaTC) in a descending order. The difference in protein solubilization of NaDC and NaGC was further characterized by the release of 5'-nucleotidase (5'-ND), a membrane-bound enzyme, and lactate dehydrogenase (LDH), an intracellular enzyme, in the perfusate. While both NaDC and NaGC caused comparable 5'-ND release from nasal membrane, intracellular LDH release was significantly higher with NaDC. The greater protein and LDH solubilizing effects of NaDC corresponded well with its faster rate of disappearance from the nasal perfusate. Therefore, the dihydroxy bile salt NaDC tends to cause intracellular damage and cell lysis, whereas the trihydroxy bile salt NaGC appears to produce primarily mucosal membrane perturbations. Linoleic acid in the form of soluble mixed micelles with glycocholate caused a further increase in nasal protein release. However, the rate and extent of nasal membrane protein release by the mixed micelles composed of 15 mM glycocholate and 5 mM linoleic acid were significantly lower than those caused by either deoxyholate or STDHF at the same concentrations. Nasal absorption of acyclovir, a non-absorbable hydrophilic model antiviral agent, was found to be enhanced in the presence of conjugated trihydroxy bile salts and bile salt-fatty acid mixed micelles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409403 TI - Influence of gastrointestinal site of drug delivery on the absorption characteristics of ranitidine. AB - The absorption characteristics of ranitidine after delivery to three locations in the gastrointestinal tract were compared in an open-label study of eight healthy males. Subjects received ranitidine HCl (150 mg) for injection via a nasoenteric tube directly into their stomach, jejunum, or cecum sequentially in three separate periods (24 hr apart). Plasma samples were collected at periodic time intervals for 12 hr following each dosing and analyzed for ranitidine concentration by high-pressure liquid chromatography. Mean concentrations following cecal dosing were lower (P less than 0.05) than concentrations following gastric or jejunal dosing at each sampling time except baseline. Mean concentrations following gastric and jejunal dosing were similar except at 2 hr (gastric greater than jejunal). Mean pharmacokinetic parameters for cecal administration were different (P less than 0.05) from either the gastric or the jejunal periods with the exception of Tmax. There was no difference in any pharmacokinetic parameter after gastric or jejunal dosing. The relative bioavailability after cecal administration was less than 15% of that observed after administration into the stomach or jejunum. Additionally, Wagner-Nelson analysis indicated that the rate of ranitidine absorption was much slower following cecal administration than after gastric or jejunal dosing. Two plasma concentration peaks were observed in three of eight subjects after gastric dosing, in eight of eight subjects after jejunal dosing, and in zero of eight subjects after cecal dosing. These data demonstrate that the absorption profile of ranitidine is equivalent, in extent and duration, after delivery to the stomach or jejunum, while absorption from the cecum is significantly less.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409404 TI - Quantitative analysis of mercaptoundecahydrododecaborate by Fourier transform infrared spectroscopy. AB - Mercaptoundecahydrododecaborate (BSH) is an important agent in boron neutron capture therapy (BNCT) of various cancers. A simple and rapid analytical method for the measurement of mercaptoundecahydrododecaborate in aqueous solution and in urine by Fourier transform infrared spectroscopy has been developed. A thin pathlength sampling apparatus was used to minimize the strong absorption of water. The subtraction of water absorbance from sample spectra resolved a B-H band at 2493 cm-1. The quantitative measurement of BSH concentration was carried out by integrating the B-H band above baseline in the range of 2534-2440 cm-1. The lower limit of measuring the concentration of sodium BSH (Na2B12H11SH) in our experiment was 10 micrograms/ml (about 5 ppm of boron). This method measures the hydroborate (B-H) concentration instead of total boron and, thus, may be utilized to measure the BSH concentration in in vivo samples for metabolic studies. PMID- 1409405 TI - Solid-state stability studies of 13-cis-retinoic acid and all-trans-retinoic acid using microcalorimetry and HPLC analysis. AB - The solid-state stabilities of 13-cis-retinoic acid and all-trans-retinoic acid in the presence and absence of oxygen were investigated. The samples were first evaluated using microcalorimetry. The rate laws of different samples under different conditions were deduced from the shapes of the heat flow curves, and the activation energies of the reactions were determined from Arrhenius plots. Under an air atmosphere, the decomposition of 13-cis-retinoic acid is an autocatalytic reaction, while all-trans-retinoic acid undergoes a zero-order process. The degradation of the two compounds at a selected elevated temperature was also determined utilizing HPLC analysis. This technique confirmed the decomposition kinetics. Hence, their half-lives and shelf lives at room temperature could be calculated. Under a nitrogen atmosphere, the microcalorimetric experiment showed a first-order phenomenon for both samples, but HPLC analysis showed no degradation, suggesting that the two samples, in the absence of oxygen, undergo only a physical change. PMID- 1409407 TI - A new application chamber for skin penetration studies in vivo with liquid preparations. PMID- 1409406 TI - An unexpected hydrolysis pH-rate profile, at pH values less than 7, of the labile imide, ICRF-187: (+)-1,2-bis-(3,5-dioxopiperazin-1-yl)propane. AB - The hydrolysis of the cardioprotectant and anticancer agent, ICRF-187 (or ADR 529) and the structurally similar model compound, 4-methylpiperazine-2,6-dione (4 MP), was investigated in the acid to neutral pH range at 25 degrees C and an ionic strength of 0.5 (sodium chloride). Their solution stability was shown to be compromised compared to 3-methylglutarimide (3-MG) and other imides. It appears that the tertiary piperazine nitrogens of ICRF-187 and 4-MP significantly contributed to the instability of these compounds over this pH range. Unexpectedly, bell-shaped curves were observed in the pH-rate profiles. A change in the rate-determining step from tetrahedral intermediate formation in the weakly acidic pH region to breakdown of the tetrahedral intermediate in the more acidic pH regions was proposed as an explanation for the bell-shaped curves. The piperazine nitrogen was implicated in the hydrolytic pathways that occur within these pH regions; the mechanism of involvement was dependent on the state of ionization of the parent molecule and the tetrahedral intermediate. PMID- 1409408 TI - Analysis of pilocarpine and its degradation products by micellar electrokinetic capillary chromatography. PMID- 1409409 TI - Survey of chlorinated hydrocarbons and other organic volatile impurities in captopril raw materials and tablets. PMID- 1409410 TI - Pain on intravenous injection. PMID- 1409411 TI - The molecular basis of type I (tyrosinase-deficient) human oculocutaneous albinism. PMID- 1409412 TI - Potential of genetically engineered monoclonal antibodies for cancer immunotherapy. PMID- 1409413 TI - Association between induction of anti high molecular weight-melanoma associated antigen (HMW-MAA) immunity with mouse antiidiotypic monoclonal antibody (MoAb) MK2-23 and prolongation of survival in patients with melanoma. PMID- 1409414 TI - Expression of high molecular weight-melanoma associated antigen (HMW-MAA) in primary ALM lesions is associated with a poor prognosis. PMID- 1409415 TI - Antigens associated with tumor progression in melanocytic neoplasia. PMID- 1409416 TI - Gangliosides of human melanoma. PMID- 1409417 TI - Ganglioside expression of human melanoma and tumor progression. Ganglioside composition of a plaque and a nodule of acral lentiginous melanoma. PMID- 1409418 TI - Melanogenesis in murine melanocytes is suppressed by infection with the v-rasHa oncogene. PMID- 1409419 TI - Biological and biochemical analysis of newly identified actin in mouse B16 melanoma. PMID- 1409420 TI - The Seiji memorial lecture. Pigment stories: from vitiligo to melanomas and points in between. PMID- 1409421 TI - In situ hybridization for the analysis of fos oncogene in melanoma cells. PMID- 1409422 TI - In vitro radiobiological analysis of 10B-L-BPA for BNCT of malignant melanoma: correlation of determined 10B-content and cell killing effect. PMID- 1409423 TI - The role of oncogenes and growth factors in progressive melanoma-genesis. PMID- 1409424 TI - The use of novel antineoplastic agents to inhibit the growth and metastasis of malignant melanoma and other cancers. PMID- 1409425 TI - The significance of depigmentation. PMID- 1409426 TI - Molecular basis of type IA (tyrosinase negative) oculocutaneous albinism. AB - Type IA (Tyrosinase negative) oculocutaneous albinism (OCA) is produced by mutations of the tyrosinase gene. We have found a total of 13 different mutations associated with type IA OCA. Analysis of the distribution of the 9 missense mutations shows that most of these mutations cluster in three areas of the gene. All but one of these mutations involve amino acids that are conserved between the mouse and human. Two clusters involve the copper A and copper B binding sites, and could disrupt the metal ion-protein interaction necessary for enzyme function. The third cluster is in exon I and could represent an important functional domain of the enzyme such as the tyrosine binding site. The deletion or insertion frameshift mutations are distributed throughout the coding region and do not appear to cluster. We conclude that a diverse number of mutations are responsible for type IA OCA and many individuals are compound heterozygotes for mutations responsible for this genetic disease (Table 3). PMID- 1409428 TI - Crustacean pigment-dispersing hormones: chemistry, distribution and actions. PMID- 1409427 TI - Integumental pigmentary factors of lower vertebrates--models for human hypo- and hypermelanoses. PMID- 1409429 TI - The mouse pink-eyed unstable mutation: a DNA duplication revealed by genome scanning. PMID- 1409430 TI - Asymmetric pigmentation and pigment disorders in pleuronectiformes (flounders). PMID- 1409431 TI - Epidemiology of malignant melanoma in central Europe: risk factors and prognostic predictors. Results of the Central Malignant Melanoma Registry of the German Dermatological Society. AB - The Central Malignant Melanoma Registry (CMMR) of the German Dermatological Society was established in 1983, and 7789 cutaneous malignant melanomas (CMM) were registered by 35 dermatological departments in Germany, Austria and Switzerland until the end of 1989. Population-based incidence rates, risk factors for developing CMM and prognostic parameters for predicting the final outcome were investigated in separate multicenter studies performed by the CMMR. Among the 7789 CMM registered, there was a preponderance of females (57.7%) versus males (42.3%). The age distribution peaked in the 5th and 6th decade of life for both sexes with a mean age of 52 years. The mean detection age was 50 years for superficial spreading melanoma, 53 for nodular melanoma, and 65 for lentigo maligna melanoma. Mean tumor thickness decreased from 2 mm in 1983 to 1.5 mm in 1989, indicating better CMM-awareness of the population and the medical community in this area. 90% of the patients presented with clinical stage I CMM without detectable metastases at first diagnosis. The incidence of CMM in Berlin (West) was assessed based on 960 cases diagnosed between 1980 and 1986. The incidence increased by 49% between 1980-81 and 1985-86, and the age standardized-incidence rate (European standard population) was 9.8 for males and 7.8 for females per 100,000 inhabitants and year in 1985-86. Mortality rates decreased in this period from 3.5 to 2.6 for males and slightly increased for females from 1.2 to 1.6 per 100,000 inhabitants and year. A case control study on the relative risk (RR) for developing CMM revealed the total number of melanocytic nevi (MCN) to be the strongest risk predictor (15x -50x increased RR), followed by the presence of dysplastic MCN (7x increased RR) and the skin type I (2x increased RR). Interestingly, no differences between CMM-cases and controls were found with respect to the history of sunburns or other parameters of sun exposure in this study. Multivariate analysis of 5093 stage I CMM-patients from four departments with long-term follow-up revealed that tumor thickness is the strongest predictor of survival with an almost linear correlation to the risk of death for tumor thickness up to 6 mm with no further increase in mortality for higher tumor thickness. The best classification of tumor thickness for survival prediction was less than or equal to 1 mm, 1.01-2 mm, 2.01-4 mm and greater than 4 mm in our data set on 5093 patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1409432 TI - Epiluminescent microscopy: a score of morphological features to identify malignant melanoma. PMID- 1409433 TI - Skin depigmentation by hydroquinone: a chemical and biochemical insight. PMID- 1409434 TI - A post melanosomal era: control of melanogenesis and melanoma growth. PMID- 1409435 TI - The stability of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid in human urine. AB - 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid are important intermediate metabolites in the formation of cutaneous melanin pigment. Since they both are serious candidates as markers of melanoma progression, their stability in urine has been investigated during storage at various conditions. The results show that storage at -20 degrees C is necessary. Both compounds are nonstable at room temperature, particularly if the urine was not acidified to pH 4-5. Reference levels were obtained from analysis of urine from 31 men and 40 women. The mean (SD) excretion of 5-S-cysteinyldopa was 32 (12.5) mumol/mol creatinine (women). Corresponding figures for 6H5MI2C were 23 (10.3) and 24 (8.1) mumol/mol creatinine for men and women respectively. PMID- 1409436 TI - Purification and characterization of dopachrome tautomerase (DT). PMID- 1409438 TI - Bio-analytical studies of eumelanins. I. Characterization of melanin the particle. PMID- 1409437 TI - Regulatory factors of pheo- and eumelanogenesis in melanogenic compartments. AB - Melanogenesis, i.e., synthesis of melanin and melanosomes, is a "cascade" of event which is channelled by internal and external regulatory factors. The recognition and selection of this information and subsequent differentiation of melanogenesis (melanin type and melanosomal development) would be regulated significantly by melanosomal membrane. The melanogenesis type could be switched relatively easily by UV light, hormone, and availability of tyrosinase substrate. The role of sulphydryl compounds as a regulatory factor in melanogenesis type (in particular for pheomelanogenesis) may not be tied to its absolute presence or absence, but rather, to the effective concentration within the melanocyte at a given time. It is, therefore, probable that the morphogenesis of melanosomes may not follow immediately in response to melanogenesis-type changes, hence the melanocyte revealing more often mosaic forms of melanosomes in nature after exposure to non-genetic factors. The switch of melanogenesis would be significantly controlled by structural and functional availability of vesiculoglobular bodies which are encoded or associated with HMSA-5 (69 kDa) glycoprotein. This HMSA-5 protein shares a significant homology with gp75 "b locus" protein. However, because of our hypothesis that vesiculoglobular bodies carry post- (and pre-) tyrosinase regulatory factors involving in both pheo- and eumelanogenesis, the term "b-protein" which focuses only on eumelanogenesis may not be applied to HMSA-5. PMID- 1409439 TI - The shift from physiological genetics to molecular genetics in the study of mouse tyrosinase. PMID- 1409440 TI - Molecular structure of the tyrosinase gene. PMID- 1409441 TI - Recent advances in the molecular biology of pigmentation: mouse models. PMID- 1409442 TI - Tyrosinase abundance and activity in murine hairbulb melanocytes of agouti mutants (C57BL/6J-a/a, Ay/a, and AwJ/AwJ). PMID- 1409443 TI - The nature of tyrosinase isozymes. PMID- 1409444 TI - Identification of mutations in the pigment cell-specific gene located at the brown locus in mouse. AB - The pigment cell-specific gene, located at the brown (b)-locus in mouse, encodes the protein that determines the type of melanin synthesized. This protein is known as tyrosinase-related protein, but here we tentatively term it b-locus protein to avoid confusions with the related sequence cross-hybridizing to the tyrosinase gene. In order to identify the mutation at the b-locus, we have cloned and characterized the b-locus protein gene of BALB/c mouse (b/b, c/c). The gene is about 18 kb long and organized into 8 exons and 7 introns. Sequence analysis of the b-locus protein gene reveals four base changes within the protein-coding regions: two missense mutations and two silent mutations. Two missense mutations result in the Cys to Tyr substitution at position 86 (codon 110) and the Arg to His substitution at position 302 (codon 326) of a b-locus protein molecule. Using allele-specific amplification, we confirmed that these missense mutations are actually present in the genomic DNA of two b-mutant strains examined, BALB/c and DBA/2 (b/b, C/C) mice, suggesting that these mutations are specific for the mutant mice at the b-locus. Moreover, we are able to show that the b-locus protein containing Tyr 86 is not reactive with the anti-b-locus protein monoclonal antibody, TMH-1, in transient expression assays. PMID- 1409445 TI - Molecular bases of tyrosinase-negative oculocutaneous albinism: a single base insertion or a missense point mutation in the tyrosinase gene. AB - We have identified two different mutations in the tyrosinase genes of Japanese patients with tyrosinase-negative oculocutaneous albinism (OCA). One is a single base insertion in the exon 2 of the tyrosinase gene that shifts the reading frame and introduces a premature termination codon (TGA) after the amino acid residue 298 (codon 316). The other is a G to A transition at residue 312, leading to a single amino acid substitution, arginine at position 59 (codon 77) to glutamine. The promoter activity of the patients' tyrosinase genes was evaluated in the cell free transcription system prepared from pigmented melanoma cells, indicating that the patients' genes were accurately transcribed in vitro. It is therefore conceivable that the tyrosinase gene is expressed in their melanocytes. Furthermore, transient expression of the mutated genes indicates that the truncated tyrosinase or the tyrosinase containing glutamine 59 is unable to form melanin in melanocytes. We therefore propose that these mutations in the tyrosinase genes lead to a phenotype of tyrosinase-negative OCA. PMID- 1409446 TI - Materia melanica: further dark thoughts. AB - The view is advanced that melanogenesis arose evolutionarily as a detoxification pathway for intrinsically-generated orthoquinones. The primary impetus for the production of orthoquinones may have been their general antibiotic properties and the utility of these chemical species in forming covalent cross-links between proteins, as illustrated by cuticular sclerotization in insects. It is argued that polymerization to give rise to visible pigments may have originated as a pathway for the inactivation of orthoquinones. The possible evolutionary advantages accruing from the generation of melanin are discussed with special reference to acuity of photoreceptors and the physico-chemical properties of melanin, as well as the contribution of melanin to protective colouration or display. PMID- 1409447 TI - B700 antigen as a component of an antimelanoma vaccine: formalinized extracellular antigens. AB - Formalin fixation has enjoyed widespread use in the preparation of antibacterial and other vaccines, but rather less use in antitumor vaccines. Previous studies from our laboratories have demonstrated the efficacy of antimelanoma vaccines in mice, produced from formalinized antigens shed by cultured melanoma cells. In this study, we provide evidence that the immunodominant component of that vaccine is the well-characterized B700 melanoma antigen. PMID- 1409448 TI - Synthesis and characterization of melanins from dihydroxyindole-2-carboxylic acid and dihydroxyindole. AB - Several studies have confirmed that a melanocyte-specific enzyme, dopachrome tautomerase (EC 5.3.2.3), catalyzes the isomerization of dopachrome to 5,6 dihydroxyindole-2-carboxylic acid (DHICA) (Pawelek, 1991). Here we report that DHICA, produced either enzymatically with dopachrome tautomerase or through chemical synthesis, spontaneously polymerized to form brown melanin that was soluble in aqueous solutions above pH 5. Under the same reaction conditions, solutions of either DOPA, DOPAchrome, or 5,6-dihydroxyindole (DHI) formed black, insoluble melanin precipitates. When DHICA and DHI were mixed together, with DHICA in molar excess, little or no precipitation of DHI-melanin occurred and the rate and extent of soluble melanin formation was markedly enhanced over that achieved with DHICA alone, suggesting co-polymerization of DHICA and DHI. With or without DHI, DHICA-melanins absorbed throughout the ultraviolet and visible spectra (200-600 nm). The DHICA-melanins precipitated below pH 5, at least in part because of protonation of the carboxyl groups. DHICA-melanins could be passed through 0.22 micron filters but could not be dialyzed through semi permeable membranes with exclusion limits of 12,000-14,000 daltons. HPLC/molecular sieve analyses revealed apparent molecular weights ranging from 20,000 to 200,000 daltons, corresponding to 100-1,000 DHICA monomers per molecule of melanin. DHICA-melanins were stable to boiling, lyophilization, freezing and thawing, and incubation at room temperature for more than 1 year. The natural occurrence of oligomers of DHICA was first reported by Ito and Nichol (1974) in their studies of the brown tapetal pigment in the eye of the sea catfish (Arius felis L.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409449 TI - Melanin biosynthesis from dopamine. II. A mass spectrometric and collisional spectroscopic investigation. AB - Electron impact (EI) and fast atom bombardment (FAB) mass spectrometry together with collisional activation (CA) experiments were applied to the study of the oxidation pathway of dopamine by tyrosinase. In order to prevent attachment of the protein to the highly reactive intermediates, ultrafiltration was employed to remove the enzyme at different reaction times. FAB, privileging molecular species formation, was successfully used for identification of transient intermediates and their relative concentrations with respect to time, directly in the reaction mixture. The presence of isobaric molecular species made chromatographic separation necessary. Further EI mass spectrometry and collision spectroscopy led to structural identification of pure components. Of these, dopamine-o-quinone, leucoaminochrome, and aminochrome semiquinone were characterized for the first time as real intermediates in dopamine melanogenesis, in agreement with previous hypotheses. This approach elucidated the pathway of dopamine melanogenesis. PMID- 1409450 TI - Melanin standard method: particle description. AB - Melanin isolated from the ink sac of Sepia officinalis (Sepia melanin) has been proposed as a standard for natural eumelanin. There are no standard methods for the isolation, purification, and storage of melanins. Mild methods designed to preserve the native composition and structure of melanin are needed. The specific aim of the present work, using Sepia melanin, was to develop a mild and generally applicable protocol for the isolation and purification of melanins. It is well established that melanin polymers contain a large number of free carboxylic acid residues. These anionic residues are responsible for the cation exchange properties observed for melanins. Heating melanins with hydrochloric acid at reflux has been demonstrated to lead to extensive decarboxylation. Indeed, heat alone has been shown to cause decarboxylation, and care must be exercised to avoid such conditions. By analogy with cation exchange resins, melanins should be isolated and named according to the associated counterion (e.g., Sepia melanin- K+ form). The method reported here avoided extremes in pH and temperature, and was designed to yield melanin in the K+ form. Physical disaggregation of particulate melanin using a wet milling step was also found to facilitate removal of significant quantities of adsorbed protein. The following physical parameters were used to monitor the purification and to characterize the resultant melanin: pH, conductance, particle size, and diffuse reflectance spectroscopy. PMID- 1409451 TI - Melanin standard method: empirical formula. AB - Melanin isolated from the ink sac of cuttle fish (Sepia melanin) is a proposed standard for natural eumelanin. Sepia melanin isolated by a standard protocol was submitted for both elemental analysis and quantitative amino acid analysis. The contribution of the detected amino acids to the elemental composition is subtracted from the total elemental analysis, and the resultant elemental composition reflects the composition of the Sepia melanin backbone chromophore. The assumption is made that, for eumelanins, there is only one nitrogen atom per monomeric unit, and thus, the empirical formula for the average monomeric Sepia melanin backbone chromophore was determined. Three key parameters can be determined for any melanin sample; namely, the molar C/N for the average monomeric unit, the formula weight of the average monomeric unit, and the total percent composition of amino acid residues. Three commonly used melanin preparations, namely, natural Sepia melanin, melanin prepared by the in vitro tyrosinase catalyzed polymerization of tyrosine (tyrosine-enzymatic melanin), and a polymer synthesized by the peroxide oxidative polymerization of tyrosine (tyrosine-chemical melanin), have been subjected to this standard method of characterization. Tyrosine-enzymatic and Sepia melanin are quite similar and tyrosine-chemical melanin is fundamentally different from the other two melanins. PMID- 1409452 TI - [Classification of erosions of the stomach. Results of a meeting of the Study Group of Gastroenterologic Pathology of the German Society of Pathology 23 November 1991 in Frankfurt/Main]. PMID- 1409453 TI - [Histochemical immunoglobulin detection in cases of sudden infant death]. PMID- 1409454 TI - [Tumor-like calcinosis]. PMID- 1409455 TI - [Frequency of metastases and survival in histologic subtypes of pleural mesothelioma. Autopsy study of 106 cases]. PMID- 1409456 TI - [Lymph node status in colorectal cancer]. PMID- 1409457 TI - [Congenital complete AV block in SS-A and SS-B antibody positive collagenosis of the mother]. PMID- 1409458 TI - [Malignant tumor of the gastrointestinal autonomic nervous system (GAN-tumor)]. PMID- 1409459 TI - [Knowledge of the Austrian pathologist Carl Sternberg (1872-1935). Attempt at a historical presentation of clinical information about lymphogranulomatosis]. PMID- 1409460 TI - [Biphosphonates. Contribution to the treatment of malignant osteolysis]. PMID- 1409461 TI - [Effect of the captopril-hydrochlorothiazide combination on blood lipids. Study in a population of hypertensive hyperlipidemic patients]. AB - In this placebo-controlled, randomized double-blind, parallel study the effects of the fixed captopril 50 mg + hydrochlorothiazide (HCTZ) 25 mg combination on plasma lipids were assessed in 42 hypertensive, type IIa or IIb hyperlipidaemic patients on diets. Some patients received oral hypolipidaemic treatment and some did not. Blood pressure and plasma lipids levels were measured before and after 1, 2 and 3 months of treatment. From the first month onward blood pressure decreased more in the treated group than in the placebo group (P < 0.05). Neither the combination nor the placebo altered the following parameters of lipid metabolism: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A1 and apolipoprotein B. The combination was well tolerated; 2 patients in each group had one or several adverse events. The results of this study show that treatment with the captopril HCTZ combination in hypertensive, hyperlipidaemic patients has no influence on the normolipidaemic effects of diet and lipid-lowering treatment. PMID- 1409462 TI - [Mortality from cancer in France. Changes between 1950 and 1989 in the population aged 35-64]. AB - In the French population aged 35-64, cancer mortality increased yearly by 1 percent in males and decreased yearly by 0.6 percent in females between 1950 and 1989. In males, the increase is mostly due to the sites associated with tobacco and alcohol. The important increase of lung cancer is related to the increase in tobacco consumption from 4.7 g per adult per day in 1950 to 6.3 g in 1976. The increase observed in head and neck cancers is related to tobacco and alcohol. In females, the moderate decrease is due to the decrease observed in uterine cervix and stomach cancer mortality, uncompensated by the increase in breast cancer. Contrary to what is observed in the USA, there is no marked increase in lung cancer mortality for women. PMID- 1409463 TI - [Changes in the vascular wall induced by surgical glues. Experimental study]. AB - The effects on vascular tissues of two different types of surgical glue, gelatin resorcinol-formaldehyde (GRF) and fibrin (Tissucol) were tested on the rat abdominal aorta. The GRF glue induced destruction of the vascular wall: multiple inclusions of the glue were noted in the media. Conversely, the fibrin glue preserved the normal architecture of the three arterial layers. The use of GRF glue therefore should be avoided on particularly fragile tissues (e.g. coronary arteries), and it seems preferable in such cases to use the fibrin glue. PMID- 1409464 TI - [Isolated dissecting aneurysm of the superior mesenteric artery. Dysplasia, a rare cause of mesenteric ischemia. Report of a case]. AB - We report a case of successful surgical revascularization of the superior mesenteric artery in a patient presenting with intestinal ischaemia due to fibrodysplasia. This is a rare pathology, with 5 cases operated in our institution and only 16 cases reported in the literature. Angiography may show other sites of arterial dysplasia. In such cases, success depends on early surgical revascularization. PMID- 1409465 TI - [Value of corticosteroids in bacterial meningitis]. AB - Bacterial meningitis mortality largely results from the intense host inflammation response to infection. Lysis of bacteria releases bacterial components that stimulate production of cytokines. Cerebrospinal fluid concentrations of these cytokines have been shown to correlate with the severity of the meningitis in both experimental and clinical situations. Dexamethasone has an antiinflammatory effect superior to methylprednisolone. It is the only agent with which significant clinical studies have yet been performed. A recent study recommends the routine use of dexamethasone with Haemophilus influenzae meningitis. The immediate and long-term clinical profiles indicate significantly better outcomes for the dexamethasone group. It is prudent to administer dexamethasone before the first parenteral dose of antibiotic to prevent the release of bacterial components induced by bacterial lysis. The search for agents that down modulate inflammation more strongly continues. Some monoclonal antibodies are superior to dexamethasone in experimental meningitis without modification of antibiotic pharmacokinetics. PMID- 1409466 TI - [Toxoplasmosis in AIDS]. AB - Toxoplasmosis is one of the major opportunistic infections observed in France in 15 to 37 percent of HIV-infected patients. Its main manifestation is encephalitis. Other, less frequent manifestations are chorioretinitis, pneumonia or disseminated toxoplasmosis. The conventional treatment is a combination of pyrimethamine 50-75 mg/day and sulfadiazine 6-8 g/day. Acute therapy should be pursued for at least 3 weeks or until optimal response is achieved, i.e. 6 to 8 weeks in most cases. The pyrimethamine-clindamycin combination in doses of at least 2.4 g/day is a possible alternative. Other drugs are being studied, but there is still a need for new drugs active against the parasite, that could be used in humans. In HIV-infected patients treatment should be maintained lifelong to prevent relapses. Maintenance regimens use the same drugs as acute therapy but in lower doses. The main field of research is primary prophylaxis of toxoplasmosis in HIV-infected patients. PMID- 1409468 TI - [Spondylodiscitis in a cirrhotic patient with penicillin G tolerant Streptococcus bovis septicemia]. PMID- 1409467 TI - [Birth anomalies of coronary arteries. Responsibility in myocardial ischemia]. AB - Anomalous origin of the left or right coronary artery from the contralateral sinus of Valsalva with coursing between the aorta and the pulmonary trunk way cause angina, myocardial infarction or sudden death. This anomaly should be suspected especially when ischemic symptoms occur in young patients without risk factor for atherosclerosis. We believe that surgical operation after demonstration of myocardial ischemia is indicated to prevent severe myocardial ischemia or sudden death. PMID- 1409469 TI - [Urticaria vasculitis revealing renal adenocarcinoma. A paraneoplastic syndrome?]. PMID- 1409470 TI - [Pharyngeal and bronchial endoscopy in the diagnosis and treatment of sleep apnea syndromes]. PMID- 1409471 TI - [Structural approach of vascular aging]. AB - The cardiovascular system is one of those target-organ systems of senescence where the effects of physiological ageing meet the consequences, accumulated with time, of pathological disorders. In man, these two processes are not easily disentangled, and despite the advances achieved in ultrasonic techniques the approach of structural parameters remains difficult. On the other hand, the morphological and functional unicity of the vascular wall in different species is such that observations made in animals are relevant. In rats, the structure function relationship can be determined by histomorphometric analysis of the myocardium and vascular wall under standardized conditions of treatment. As the animals get older, the cardiac mass, related or not to body-weight, increases while the cardiac efficacy decreases. Hypertrophy of the heart is accompanied by a change in the enzymatic property of myosin. Simultaneously, the walls of the greater arteries become thicker, more rigid and less compliant, hypertrophy of the smooth muscle cells being an essential component of vascular wall thickening. At the same time, the collagen fraction and the amount of collagen-bound calcium increase. The elastic component decreases, at least relatively, and the elastin collagen ratio clearly diminishes with age. Altogether, these alterations are not different from those observed in human arterial hypertension. They result in a lesser permeability of the tunica media, facilitate the accumulation in the subendothelium of lipidic and/or proteinic compounds originating in plasma and constitute a link between ageing and atheromatous processes. PMID- 1409472 TI - [Molecular bases of cardiac aging]. AB - The total volume occupied by myocytes in the heart decreases with age, and this is accompanied by a loss of myocytes, by hypertrophy and, to a lesser extent, by hyperplasia of the remaining myocytes. There are differences between ventricles: the right ventricular myocytes have a greater capacity for replication than those of the left ventricle. The expression of genes coding for the 2 principal contractile proteins (myosin and actin) is modified, and there are strong resemblances between the phenotype of the aged heart and that of an adult heart with haemodynamic overload. PMID- 1409473 TI - [Aging of the arterial system]. AB - The high-pressure systemic arterial network plays a major physiological role as it buffers the impact of the blood flow wave generated by the left ventricle and transforms it into a more continuous flow in the peripheral arterioles. In ageing processes unrelated to hypertensive or vascular disease the structural properties of the arterial network are significantly altered. The collagen, elastin and smooth muscle contents of the tunica media and the geometrical arrangement of arterial wall components are constantly modified according to the subject's age. These morphometric changes are responsible for changes in the mechanical properties of the arterial walls leading to rigidity. An increase in caliber of the arterial lumen has been found in all studies; it partially compensates for the effects of arterial wall rigidity on vascular compliance, thereby limiting the haemodynamic and functional changes that occur in blood circulation. PMID- 1409474 TI - [Effects of aging on arterial function in man]. AB - The structure of arteries changes with age. Gradual disappearance of elastic fibres facilitates dilatation of the arterial lumen and increase in length of the vessels. Simultaneously, the arterial wall becomes thicker, but it is often difficult to distinguish the changes due to ageing from those caused by atherosclerosis. These structural alterations result in a greater rigidity of the arteries, which can now be evaluated by non-invasive segmental methods. This shows that ageing does not have the same functional effects on wide-caliber elastic arteries and on middle-sized muscular arteries. The increase of systolic arterial pressure observed in the elderly is a consequence of structural and functional changes in the arterial system. PMID- 1409475 TI - [Aging of heart function in animals]. AB - Most of the laboratory animals studied for cardiovascular ageing are rodents. Anatomical studies have demonstrated an increase in heart weight and volume, hypovascularization of the myocardium and, more recently, hypertrophy of myocytes. Studies on the mechanical properties of rat papillary muscle have shown that ageing is associated with reduction of myocardial distensibility, whereas the habitual parameters of contractility (Tmax and Vmax) are unchanged in terms of baseline values. On the other hand, mechanical responses to stimulation of beta-adrenoceptors are reduced. The essential change in myocardial contraction in ageing rats is its chronology: ageing is attended by a longer duration of both contraction and relaxation. Biochemical studies of old rats' myocardium have yielded a fundamental information: in this species ageing is accompanied by a change in synthesized myosin subtype. This change is identical to that observed in experimental systolic overload; it is also adaptative, as it enables oxygen consumption to be reduced during a constant work, and it explains the modifications observed in the chronology of a contraction. Studies on the "pump" function of old rats' myocardium have confirmed the appearance with age of another adaptative change: isolated hearts of old animals have a greater output in a rigid circuit while the hearts of adult rats have their output in a more compliant circuit. Altogether, experimental studies on cardiac ageing lead to the conclusion that the changes observed are similar to those due to systolic overload, the origin of which is a loss of arterial compliance. These changes are adaptative in that they reduce oxygen consumption by a myocardium with systolic overload, but the resulting changes in contraction chronology are such that the aged heart cannot deviate from a mean rate without notably widening the differential blood pressure. Thus, experimental studies of myocardial ageing have presented ageing as a contradiction between ideal adaptation to a chronic stress and reduced possibilities of adaptation to acute aggressions. PMID- 1409476 TI - [Functional coupling of the left ventriculo-arterial system and aging in man]. AB - In a haemodynamic and angiographic study at rest conducted in 25 men aged from 22 to 68 years who had no more than another risk factor for arterial disease and showed no evidence of cardiac or arterial disease several parameters were measured or calculated. Firstly, a global index of arterial system function (Ea) and its various factors: Ea = ESP/SV [ESP: left ventricular end-systolic pressure; SV: systolic volume]; Ea = (HR x TSR)+Ea' [HR: heart rate/min; TSR: total systemic resistance] where Ea' = (ESP - AoP/SV) [AoP: mean aortic pressure]. Secondly, the parameters concerning the left ventricle were the mass (m) and the m/EDV ratio [EDV: end-diastolic volume] and indices of the left ventricular systolic and diastolic functions, such as ELV = ESP/ESV [ESV: end systolic volume], kp: the volumic distensibility module of the left ventricular chamber; relations EF - o ES [EF: ejection fraction; o ES: end-systolic constraint], and kp - m/EDV as indice of left ventricular muscle distensibility. In parallel with the subjects' age, Ea increased by joint augmentation of TSR and Ea' while m, m/EDV, ELV and kp also significantly increased. The inotropic quality of the left ventricular muscle and its intrinsic distensibility were found to be decreased in a few subjects aged over 45. Ea/ELV (reverse of ejection fraction -1) tended to increase (ELV relatively less than Ea), but this increase was not significant (P = 0.10). These results show that in the ageing man the improvement observed in the ejection fraction of the left ventricular pump corresponds roughly to the degradation of the arterial system transfer function, and the arterial system-left ventricle coupling, evaluated by the Ea/ELV ratio, is maintained (better in fact than in arterial hypertension and heart failure). This improvement is achieved by increases of m and, chiefly, m/EDV which compensate for both the increase of Ea and the relative decline of left ventricular muscle contractile quality. There is a disorder of the left ventricular pump diastolic function which is due to geometric changes in the chamber and to changes in the intrinsic distensibility of the left ventricular muscle. PMID- 1409477 TI - [Cerebral blood flow. Changes in regulation with aging]. AB - In subjects without cardiovascular or neuronal diseases ageing does not seem to be accompanied by a significant fall in global cerebral blood flow at rest. Yet non-negligible changes in cerebral blood flow rate can be demonstrated by haemodynamic or metabolic stimuli. Several intra- and extracranial vascular mechanisms may be involved in these changes. During ageing, a decrease of carotid artery compliance due to parietal calcium deposition might be an important factor in the disturbance of cerebral blood flow regulatory mechanisms. PMID- 1409478 TI - [Cerebral and cardiovascular aging and brain energy metabolism. Studies with positron-emission tomography in man]. AB - Positron emission tomography (PET) is the only method that measures concomitantly in the same cerebral region the main haemodynamic (blood flow, blood volume) and metabolic (oxygen and glucose consumption) parameters, thereby providing essential data concerning the supply of substrates by circulation and their principally neuronal/synaptic use by the cells. In "healthy" (i.e. normal) ageing, there is a progressive decrease of oxygen and glucose consumption--with subsequent reduction of cerebral blood flow (CBF)--which predominates in the neocortex and suggests a dysfunction of neuronal circuits perhaps responsible for some age-related changes in cognitive functions. The metabolic depression in the neocortex seems to be accentuated during the more "common" ageing which may include cerebrovascular risk factors, lesions of the white matter in varying numbers and/or degradation of cognitive functions. Strategically located brain lesions of vascular origin (e.g. damaging of the thalamic nuclei), may produce a thalamo-cortical disconnection which induces a diffuse cortical hypometabolism associated with severe cognitive disorders. In degenerative dementias (particularly Alzheimer's disease), which include cortical and subcortical neuronal lesions (e.g. those involving the cholinergic system), there is a hypometabolism preferentially affecting the associative cortex. The cumulative effects on cortical functioning of multiple vascular lesions, superimposed on degenerative neuron loss, might account for age-related cognitive disorders in "normal" ageing as well as in the so-called "vascular" or "mixed" dementias. PMID- 1409479 TI - [Normal and pathological renal aging in animals]. AB - Ageing of the kidneys has long been associated with a fall in the number of functioning nephrons resulting in a reduction of renal blood flow and glomerular filtration. This narrow concept of age-related changes in renal function has been developed chiefly during the last few years by Brenner et al. on the basis of experimental studies conducted on rodents. According to these authors, the size and frequency of segmental and focal lesions of glomerulosclerosis increase regularly with age, and in its final phase this pathology results in occlusion of glomerular capillaries. Renal ageing, therefore, can be assimilated to the nephron reduction models obtained by surgical ablation. The hypothesis that hypofiltration in certain nephrons is compensated by hyperfiltration in healthy glomerulis, leading to a vicious circle of self-destruction, was then applied to both ageing and experimental renal impairment: the smaller the number of nephrons, the greater the filtration achieved by the remaining nephrons, a process that accelerates the probability of their destruction. Conversely, any attempt to reduce intracapillary pressure or glomerular filtration slows down the progression of renal failure. This hypothesis is supported by experiments showing that reduction of protein intake or chronic inhibition of angiotensin I converting enzyme activity are truly capable of limiting the progression of glomerulosclerosis induced in rats by partial renal mass ablation. Similarly, prolonged food restriction increases the life expectancy of rodents and almost totally prevents the occurrence of glomerulosclerosis. The experimental finding that degenerative renal lesions do not necessarily develop with age raises the problem of normal and pathological ageing. With an adequate choice of rats' food, strain and sanitary surroundings it is possible to obtain very old animals devoid of occluded glomerular capillaries and loss of nephron. What about the functional and structural changes due to ageing and not to pathology? This question has given rise to numerous studies which concluded, on the whole, that there exists a normal ageing of the kidneys without loss of nephron and that ageing is expressed by the fact that the kidneys have difficulties in adjusting themselves to disturbances in the inner environment. As regards renal functional reserve, response to the antidiuretic hormone in case of water restriction, or stimulation of the renin-angiotensin system in response to decrease of sodium intake, it is clear that the renal cells responsible for glomerular filtration, tubular transport or synthesis and release of peptidic hormones exhibit functional alterations that are age-related. The cellular and molecular mechanisms underlying these physiological changes are little known.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1409480 TI - [Renal aging in man]. AB - Renal morphological and functional changes occur in the elderly. Between the ages of 50 and 80 years the renal mass diminishes by a mean of 20 percent, to the expense of the renal cortex. Glomerular sclerosis results in a gradual fall in the number of functioning glomeruli. Simultaneously, a decrease of about 7 percent in glomerular filtration rate per decade after the age of 40 years and a 10 percent decrease in renal plasma flow per decade, and therefore an increase in filtration fraction, are observed. These haemodynamic abnormalities are accompanied by changes in tubular function, including a delay in renal adjustment to sodium overload, and above all to sodium restriction, together with a decrease in concentrating and, to a lesser extent, diluting capacity. In actual fact, the intensity of glomerular sclerosis varies considerably from one subject to another, and the decrease in glomerular filtration rate is far from being constant. These changes are perhaps not ineluctably associated with aging; they might result from pathological processes that have gone unnoticed. PMID- 1409481 TI - [Cardiovascular pathology related to aging. Role of prevention]. AB - During the last 50 years the increase of life expectancy has been dramatic in all Western countries. In France, the life expectancy in 1988 was 80.6 years for women and 72.3 years for men. In 1980, the life expectancy at the age of 60 was more than 20 years in women and 16 years in men. Side by side with this increase of life expectancy there has been a change in the structure of the causes of death. Cardiovascular diseases accounted for 15.6 percent of all causes in 1930, 31 percent in 1950 and 37.4 percent in 1980. Cardiovascular diseases therefore rank very high among the causes of mortality, and one of the principal reasons for this is ageing of the population. Studying the epidemiology of cardiovascular ageing is tantamount to determining the part played by prevention in these diseases. There are wide fluctuations in cardiovascular mortality rate according to some demographic variables: men are more affected than women, the poorer subjects more than the richer subjects, and people living in the North of France more than those living in the South. These disparities are real, irrespective of age, and they can be explained, at least partly, by differences in the prevalence of well-known risk factors. Cardiovascular ageing plays a role, probably important, in the genesis of physical and mental disabilities, but markers that would measure them precisely are lacking. The development of such indicators is a major line of research which should make it possible to evaluate the prospective results of a policy of prevention in a segment of the population where people aged 60 or more accounted for 19.1 percent in 1990 and will account for 25 percent in the year 2020. PMID- 1409482 TI - [Prevention of pathological aging. The arterial hypertension example]. AB - Studies conducted during the last decade have made it increasingly easier to distinguish between normal and pathological ageing. Previous studies on general populations had established a dogma: most of the major body functions, such as cardiac output, glomerular clearance, muscular strength, visual acuity and so forth, were supposed to decline with age. However, in recent studies on the effects of age on cardiac output all subjects with heart disease were excluded and as a result the negative correlation found between cardiac output and age disappeared, which shows that a phenomenon attributed to ageing was in fact caused by disease. This does not mean that there is no such thing as fundamental ageing, and indeed the mechanisms that maintain cardiac output are different in young and elderly subjects. These data are of more than theoretical interest, since it may be presumed that prevention, the instruments of which are already available in some fields, will modify the profile of ageing. The risk of arterial hypertension is not restricted to the classical cardiovascular diseases: it extends to other diseases, such as vascular dementia, which are potent factors of pathological ageing. Most of the controlled trials carried out in arterial hypertension have demonstrated that treating certain types of hypertension significantly reduces the morbidity and/or mortality of cardiovascular diseases. The specific properties of new antihypertensive drugs, such as angiotensin converting enzyme inhibitors, open stimulating vistas on arterial ageing. PMID- 1409483 TI - Breast and cervical cancer screening in older women: the San Diego Medicare Preventive Health Project. AB - BACKGROUND. This study presents rates and correlates of cancer screening, including mammography, clinical breast exam, breast self-examination, and Pap tests, in older women. Age was the predictor of main interest. RESULTS. Among a sample of female Medicare beneficiaries ages 65 and older, who were members of a health maintenance organization, there was a significant, inverse relationship between age and mammography adherence, while controlling for health status, physician utilization, education, and income. The proportions of subjects ages 65 74 and 75+ never having had a mammogram were 17 and 32%, respectively, and the proportions having had annual mammograms were 40 and 28%, respectively. Pap test frequency showed a trend toward an inverse relationship with age, controlling for demographic and health-related variables. In the youngest age group (65-69), 52% had annual Pap tests, whereas in the oldest group (80+), only 36% had annual Pap tests. Age did not predict frequency of clinical breast exam, and the relationship of age to breast self-examination was inconclusive. The role of the physician in promoting cancer screening is discussed. PMID- 1409484 TI - Breast cancer screening attitudes and behaviors of rural and urban women. AB - This study was carried out to assess the breast cancer knowledge, attitudes, and awareness of women age 40 to 74 in Alberta, a Canadian province of 2.4 million people. This analysis compares the attributes of 538 rural women, defined as those living between 1 and 3 hr drive from the major cities in Alberta, and 735 urban women who lived in one of these two cities. Rural women were found to have the same basic knowledge of breast cancer or perceptions of barriers to mammography, but had more negative attitudes about breast cancer itself. Despite their similar access to physician care, they were less likely to have had a recent clinical breast examination or mammogram (P less than 0.001). These differences remained when adjustment was made for demographic background variables; the adjusted prevalence rate ratio for a screening mammogram in the past 2 years was 0.52 (95% C.I., 0.43, 0.64), and for intention to have a mammogram in the next 2 years, 0.75 (0.63, 0.90). The results suggest particular program delivery strategies when planning for provision of breast screening information and service to the large subgroup of rural women. PMID- 1409485 TI - Impact of a clinical preventive medicine curriculum for primary care faculty: results of a dissemination model. AB - BACKGROUND: This study was designed to test a dissemination model for providing clinical preventive medicine (CPM) training to general internal medicine faculty across the United States. METHODS: The model incorporated direct instruction of a few faculty as seminar facilitators who, in turn, taught a CPM curriculum to their faculty colleagues, who then could teach it to housestaff and students. The CPM curriculum consisted of six seminars that focused primarily on the risk factors for chronic diseases and on behavior change methods for modifying smoking, diet, and exercise. RESULTS: Faculty who participated in the seminars had significant pre- to post-test increase in knowledge and reported self efficacy to implement CPM strategies with patients, as well as changes in CPM clinical practices. These faculty, in turn, successfully disseminated CPM information to their housestaff, who also had increases in self-efficacy and changed clinical practices regarding CPM topics. CONCLUSIONS: The successful implementation of the dissemination model attests to its viability as a mechanism for disseminating CPM curricula and increasing the emphasis on CMP issues in both clinical teaching and clinical encounters with patients. PMID- 1409486 TI - A comparison of knowledge of medical students and practicing primary care physicians about cardiovascular risk assessment and intervention. AB - BACKGROUND: Heart attack and stroke are still prevalent causes of death and disability in the U.S. adult population (1, 2). Studies (3-9) have shown that modification of hypertension, smoking, and hypercholesterolemia can reduce risks for atherosclerosis and subsequent cardiovascular events. Therefore, it is important that physicians be skilled in assessing and modifying patients' overall cardiovascular risk. This study compares acquired knowledge of second-year medical students about cardiovascular risk assessment with knowledge in a selected group of practicing primary care physicians, who are members of the medical school's clinical faculty, using a new experimental testing technique called the tailored response test (TRT). METHODS: Students performed a structured cardiovascular risk intervention on a patient in primary care clinics. Their acquired knowledge was then tested using the TRT, which contained 43 discrete judgments about a clinical case. Test scores of students and faculty were compared. RESULTS: Both students and faculty demonstrated knowledge about the most important risk factors, appropriate screening tools, and interventions. However, the selected physicians did not demonstrate knowledge of certain important risk assessment and intervention recommendations, based on national standards. Only 38% of faculty and 27% of students were aware that a "fasting" serum cholesterol is not needed for screening, 30% of faculty believed that if cholesterol was over 300 they would "probably prescribe medicine" before other intervention strategies were tried, and 32% of faculty and 30% of students would order a screening chest X-ray, which is incorrect in the case history. CONCLUSIONS: The TRT, in contrast to self-report surveys, demonstrates that important cardiovascular risk assessment and intervention knowledge, with implications for cost effectiveness in health care delivery, has not penetrated to a selected group of physicians who are members of the medical school's clinical faculty and therefore serve as role models for medical students. This is disturbing, in light of current emphases on cost effectiveness in health care. Greater undergraduate curricula and CME emphasis on cardiovascular preventive practice is needed, such that almost 100% of students and faculty demonstrate knowledge, and practice, of preventive medicine according to national standards. In turn, groups developing national standards are enjoined to design and implement effective approaches for disseminating these recommendations. PMID- 1409487 TI - Results from a statewide approach to adolescent tobacco use prevention. AB - BACKGROUND: The 1985 Minnesota Legislature established guidelines for school based tobacco-use prevention programming and provided financial incentives to school districts to encourage them to adopt a broad range of preventive measures. The Minnesota-Wisconsin Adolescent Tobacco-Use Research Project was funded by the National Cancer Institute in 1986 to evaluate the Minnesota initiative through two parallel studies. METHODS: The Four Group Comparison Study was a prospective study of 48 school "units" which were randomly assigned to one of four conditions in 1987. Baseline observations were taken in the sixth grade in 1987, interventions were delivered in the seventh grade, and follow-up observations were taken in the seventh, eighth, and ninth grades. The Four Group Comparison Study was designed to evaluate the three middle-school interventions that were most widely adopted by Minnesota school districts as a result of the 1985 legislation. The Two State Comparison Study was a serial cross-sectional study of representative districts in Minnesota and Wisconsin. Annual surveys of ninth graders were conducted from 1986-1990. The Two State Comparison Study was designed to determine whether tobacco-use patterns changed in Minnesota relative to Wisconsin following the Minnesota legislation. RESULTS: The prospective study indicated that none of the interventions was more effective in reducing adolescent tobacco use compared with a randomized control group. The serial cross sectional study revealed that there was a modest net decline in Minnesota relative to Wisconsin from 1986 to 1990, but that it was within the range of chance variation. CONCLUSIONS: Taken together, these results indicate that this legislative initiative was insufficient to reduce adolescent tobacco use statewide during the 5-year study period. Together with results from other recent studies, they suggest that even more intensive efforts may be required to effect widespread reductions in adolescent tobacco use. PMID- 1409488 TI - Calcium intake in youth: sex, age, and racial differences in NHANES II. AB - METHODS: Data from the NHANES II survey were used to determine whether the calcium intake of children ages 3-18 met the minimum recommended daily allowance. In addition, the impact of age, race, sex, and socioeconomic status on calcium intake and the density of calcium intake was explored. RESULTS: The results indicated significant differences between groups of children based on age, sex, and race (P less than 0.05). Males across all age groups (3-5, 6-7, 8-10, 11-12, 13-18) had a higher calcium intake than females. In addition, calcium intake levels among males always met or exceeded the minimum RDA. Levels among all blacks started below the minimum RDA in the age group 3-5. During the adolescent years, calcium intake again fell below the RDA for black males and for females of both races, with the calcium intake of the adolescent females resembling that of the group ages 3-5. In a multiple regression model sex, age, race, and total energy intake predicted 49% (P less than 0.0001) of the variance in calcium intake. Socioeconomic status (using parents' reported income) was not a significant predictor. Another regression model was used to examine the relationship among age, race, sex, and socioeconomic status and its effect on the density of calcium intake (mg/kcal). While the overall model was significant (P less than 0.0001) it accounted for only 3.5% of the variance. CONCLUSION: Age, sex, and race of the child significantly predicted the density of calcium (P less than 0.05); however, parents' gross income did not (P less than 0.81), indicating that income level does not contribute to explaining these differences. PMID- 1409489 TI - Elderly health beliefs, attitudes, and maintenance. AB - BACKGROUND: Why older persons engage in varying amounts of health maintenance activity is becoming both an increasingly important policy issue and a topic of interest to health services researchers. Such activity may help the elderly to delay the onset of the health-related problems associated with aging, maintain if not improve their functional abilities, and perhaps improve their quality of life. METHODS: Using a conceptual model largely based upon the health belief model, this study sought to examine predictors of variability of health maintenance activity among older persons. The project included cross-sectional data drawn from the first phase of a multiyear panel study of elderly community residents. RESULTS: Results of ordinary least-squares and logistic regression analyses of seven types of health maintenance activity suggest that health beliefs are an important consideration but that other variables, namely, type of insurance plan and select sociodemographic factors, also had significant impacts. Another consistent finding was that each of the types of health maintenance activity was associated with different types of predictor variables. CONCLUSION: These findings suggest that in order for levels of health maintenance activity to be increased, intervention programs need to be targeted toward specific types of health beliefs and need to take into account the importance of social differences. PMID- 1409490 TI - Environmental effects on chromosomes in oncology and radiology department personnel. AB - Long-term, low levels of antineoplastic drugs and ionizing radiation in the work environment may have genotoxic effects on chromosomes in personnel. The effects of ionizing radiation is acknowledged in occupational medicine and therefore various measures have been undertaken to prevent such effects. However, there are no protective measures for workers exposed to antineoplastic drugs. In this study metaphase chromosome preparations were analyzed in 126 nurses and radiology technicians. They were divided into three equal groups. The first group consisted of shift nurses in an oncology department handling antineoplastic drugs. The second group consisted of radiology technicians in a radiology department and the third group acted as controls. Structural chromosomal aberrations were increased among those nurses exposed to antineoplastic drugs in comparison with technicians (P less than 0.05) and controls (P less than 0.01), respectively. PMID- 1409492 TI - Chemopreventive effects of green tea components on hepatic carcinogenesis. AB - Catechin components of green tea have been shown to possess anticarcinogenic properties possible related to their antioxidant activity. In the present study, a catechin containing green tea extract (GTE) was examined for its effect on three previously defined properties of liver tumor promoters, induction of cytolethality, inhibition of gap junctional intercellular communication, and induction of cell proliferation. Hepatocytes from male B6C3F1 mice were isolated and placed in primary culture. The effects of GTE of oxygen free radical-induced cytolethality was examined by coincubating GTE with the oxygen radical generating compounds paraquat, glucose oxidase (GO), and xanthine oxidase (XO). GTE prevented the induction of hepatocyte cytolethality by GO, XO, and paraquat in a dose-responsive manner. Similarly, GTE prevented the inhibition of gap junctional mediated intercellular communication (measured by lucifer yellow dye coupling) by phenobarbital, lindane, and paraquat in a dose-dependent manner. The effect of GTE on hepatocyte DNA synthesis was examined in male mice containing preneoplastic liver lesions induced by diethylnitrosamine. GTE significantly decreased the labeling index in hepatic preneoplastic foci from animals treated with phenobarbital for 7 days. These studies suggest that the previous reported anticarcinogenic activity of green tea may be related to its effect on the tumor promotion stage of the cancer process. PMID- 1409491 TI - Anticarcinogenic effects of (-)-epigallocatechin gallate. AB - BACKGROUND: Our research objective is to develop nontoxic cancer chemopreventive agents and to apply these agents in treating humans. We are identifying agents that inhibit the process of tumor promotion in two-stage carcinogenesis experiments on mouse skin. METHODS: We review (a) the inhibitory effect of penta O-galloyl-beta-D-glucose (5GG) on tumor promotion by teleocidin, one of the 12-O tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters (5GG is structurally similar to (-)-epigallocatechin gallate (EGCG) and is isolated from hydrolyzed tannic acid); (b) the inhibitory effects of EGCG, the main constituent of Japanese green tea, on tumor promotion with two tumor promoters, teleocidin and okadaic acid, a non-TPA-type tumor promoter; (c) the mechanisms of action of EGCG, a single application of which reduced the specific binding of [3H]TPA and [3H]okadaic acid to a particulate fraction of mouse skin; and (d) the anticarcinogenic effects of EGCG on duodenal carcinogenesis induced by N-ethyl-N' nitro-N-nitrosoguanidine in male C57BL/6 mice. EGCG is a nontoxic compound. CONCLUSION: We believe that the main constituent of Japanese green tea, EGCG, is a practical cancer chemopreventive agent available in everyday life. PMID- 1409493 TI - Antioxidative effect of polyphenol extract prepared from various Chinese teas. AB - METHODS. Twelve different types of Chinese teas, including green, semifermented, and black tea, were studied for their antioxidant activities and active components. Compositions of (-)-epicatechin, (-)-epigallocatechin, (-) epicatechin gallate, (-)-epigallocatechin gallate, and gallic acid were identified by fast atom bombardment-mass spectrometry and high-performance liquid chromatography-mass spectrometry and quantified by high-performance liquid chromatography. Antioxidant activities in lard were measured by the Rancimat method. RESULTS. The results showed that both yields of polyphenol extract and antioxidant activities varied with different tea processing methods. It was found that (-)-epigallocatechin gallate, (-)-epigallocatechin, and (-)-epicatechin gallate inhibited soybean lipoxygenase at the IC50 values ranging from 10 to 20 microM. PMID- 1409494 TI - Green tea consumption and serum lipid profiles: a cross-sectional study in northern Kyushu, Japan. AB - METHODS. The relation between green tea consumption and serum lipid concentrations was examined using cross-sectional data on 1,306 males who received the retirement health examination at the Self-Defense Forces Fukuoka Hospital between October 1986 and December 1988. RESULTS. After adjustment for rank, smoking, alcohol use, physical activity, and body mass index, serum total cholesterol levels were found to be inversely related to the consumption of green tea while no association was noted with serum triglycerides and high-density lipoprotein cholesterol. Adjusted mean concentrations of total cholesterol were 8 mg/dl lower in men drinking nine cups or more per day than in those consuming zero to two cups per day. Serum cholesterol levels were inversely associated with traditional Japanese dietary habits (intake of rice and soy bean paste soup) and positively associated with Westernized habits. Additional adjustment for these dietary variables did not alter the inverse relation between green tea and total cholesterol. PMID- 1409495 TI - Association of serum lipoproteins and health-related habits with coffee and tea consumption in free-living subjects examined in the Israeli CORDIS Study. AB - BACKGROUND: A positive association between coffee consumption and serum cholesterol levels has been demonstrated and recent results indicate that this may be due to a lipid-rich fraction present mainly in boiled coffee. The possible effects of tea consumption are less clear, although evidence has been presented which suggests that tea drinkers have lower cholesterol levels. The associations between serum lipids and lipoproteins and coffee and tea consumption were examined in the Israel CORDIS study. METHODS: Employees of 21 factories were screened for cardiovascular disease risk factors between 1985 and 1987. Detailed data on coffee and tea consumption and serum lipids and lipoproteins were available for 3,858 men and 1,511 women. RESULTS AND CONCLUSIONS: Consumption of five or more cups of coffee per day was reported by 10.1% of men and 8.7% of women, whereas only 3.4% of men and 2.2% of women consumed similar quantities of tea. After controlling for a number of potential confounders, coffee consumption (particularly "mud" coffee) was strongly and positively associated with higher serum total and low-density lipoprotein cholesterol levels in both sexes (consumers of five or more cups per day had cholesterol levels up to 18 mg/dl higher than abstainers) and with high-density lipoprotein cholesterol in women. There was a nonsignificant negative association between tea consumption and serum cholesterol (cholesterol levels about 5 mg/dl more in abstainers than in those consuming five or more cups per day). In general, more negative health-related habits were reported with increased coffee consumption, whereas this relationship was not found for tea drinking. The relatively small percentage of heavy tea drinkers limits the conclusions that one can draw from this study and controlled trials are needed to evaluate possible lipid-lowering effects of tea consumption. PMID- 1409496 TI - Tea consumption. relationship to cholesterol, blood pressure, and coronary and total mortality. AB - BACKGROUND AND METHODS: The relation of tea to cholesterol, systolic blood pressure, and mortality from coronary heart disease and all causes was studied in 9,856 men and 10,233 women without history of cardiovascular disease or diabetes. All men and women 35-49 years of age from the county of Oppland (Norway) were invited to participate; the attendance rate was 90%. RESULTS: Mean serum cholesterol decreased with increasing tea consumption, the linear trend coefficient corresponded to a difference of 0.24 mmol/liter (9.3 mg/dl) in men and 0.15 mmol/liter (5.8 mg/dl) in women between drinkers of less than one cup and those of five or more cups/day, when other risk factors were taken into account. Systolic blood pressure was inversely related to tea with a difference between the same two tea groups of 2.1 mm in men and 3.5 mm in women. Altogether 396 men and 237 women died from all causes, and of these 141 and 18, respectively, died from coronary heart disease during the 12-year follow-up period. The mortality rate was higher (not statistically significant) among persons drinking no tea or less than one cup compared with persons drinking one or more cups/day. This applies to men and women and to coronary heart disease and all-cause mortality. For men, the relative risk (one or more versus less than one cup) for coronary death from Cox regression was 0.64 (95% CI:0.38, 1.07). PMID- 1409497 TI - [Video bronchoscopy--the electronic view of the bronchus]. AB - The optical resolution in the fibrescopes commonly in use is limited by the number and length of glass fibres used in the endoscopes. In the videoscope--i.e. in the direct videoscopy--the endoscopic picture is transformed already in the tip of the endoscope into electronic signals which can be guided through electrical wire nearly free from losses. This results in an enormous improvement of the image quality. Some problems arise from the adjustment of the light intensity yielding too much brightness in the short-distance and darkness in the depth. Furthermore, the work channel of the prototype we used is still too small. The investigation with this new technique requires an increased coordinative effort between the handling of the instrument and the picture on the monitor; but with some practice one becomes familiar with it. The pictures of the bronchial wall are extremely brilliant. Unusual structures of bronchial mucosa can be analyzed. Microscopic endoscopy seems to be only a short step away. Digital processing of the electronic image offers extraordinary perspectives for the future. PMID- 1409498 TI - [Negative cortisone attitude in patients with bronchial asthma]. AB - Patients with bronchial asthma often exhibit irrational fears of cortisone medication beyond justified worries about side-effects. A negative cortisone image, which means overemphasizing the damaging and threatening aspects of cortisone, often underlies non-compliant illness behaviour. In the present study, cortisone image was investigated in 54 patients with bronchial asthma before and after participation in the Dusseldorf Asthma treatment and teaching programme (ATTP) and one year later. By participating in ATTP, a significant reduction of the negative cortisone image and thus a more realistic view of cortisone could be achieved in most patients. This effect was also evident at the follow-up examination one year later. On the other hand, persistence of a negative cortisone image in a subgroup of patients turned out to be a potent predictor of later non-compliant illness behaviour. Psychological implications of a persistent negative cortisone image are discussed. PMID- 1409499 TI - [Comparison of six peak flow meters for patients]. AB - Five meters of six models of peak flowmeters have been checked by 40 measurements each in series with a pneumotachograph. There were no substantial differences between the five meters of one type, but the various models showed a different scatter, partly due to differences in the applied flow pattern. We prefer those peak flowmeters with less influence of the flow pattern. PMID- 1409500 TI - [Case report: endoscopic resection of a 5 cm intrathoracic lipoma]. AB - Technical possibilities of operative thoracoscopy are demonstrated on the occasion of the presentation of an endoscopic resection of a benign intrathoracic tumour. Thoracic video-endoscopy is definitely a useful constituent of the treatment of defined pleural or pulmonary processes, since it can be used in addition to biopsy (which serves to assure the correct diagnosis) without rendering the diagnostic procedure more complicated to any significant extent. PMID- 1409502 TI - [35th congress of the German Society for Pneumology and Tuberculosis. Wiesbaden, 23-26 September 1992. Abstracts]. PMID- 1409501 TI - [With reference to: Pneumology 46 (1992) 89-91]. PMID- 1409503 TI - [Social significance of research studies in the fields of phthisiology and pulmonology in Uzbekistan]. AB - The direction of research work in phthisiology and pulmonology is determined by the epidemiologic situation for tuberculosis and CNPD in the republic. The results of a complex research work in phthisiology and pulmonology carried out in the rural areas of Uzbekistan, and in the cotton--growing regions in particular, are given. Practical significance of this work is stressed, which comprises direct inspection of the tuberculosis infection foci and subjects in contact and subsequent accomplishment of preventive and health--improvement measures, comprehensive screening of the rural population for tuberculosis and CNPD detection, conduction of chemotherapy and pathogenetic and surgical treatment of tuberculosis patients. The results of research into phthisiology and pulmonology will make the basis of the national program with respect to tuberculosis in Uzbekistan. PMID- 1409504 TI - [Use of computer technology for teaching phthisiology and pulmonology at medical institutes]. AB - The experience of computer technology application at the Phthisiology Department of the Kazan Medical Institute over the last 5 years was generalized. Four classes of the teaching programs were described: program control of the accumulated experience, diagnostic search, a mathematical model of an emergency situation and expert medical systems. Preference is given to the latter two types of programs. It is emphasized that application of the IBM-compatible systems as the most prevalent in clinical practice is promising. Description of the specific programs is presented. PMID- 1409505 TI - [Characteristics of diagnosis, clinical aspects and clinical course of tuberculosis in adolescents with concomitant diseases]. AB - The authors present the data on special features of the course of tuberculosis in adolescents having other diverse conditions such as nonspecific pulmonary diseases and congenital abnormalities, prior acute respiratory diseases and concurrent iron deficiency anemia. The combination of tuberculosis with other diseases results in a longer course of tuberculosis with slow clinical and X-ray dynamics and in a number of cases (++prior acute respiratory diseases) in bouts of the specific process. The favourable outcomes of the disease are determined by the correct combined treatment of tuberculosis and concurrent diseases. When tuberculosis runs along with congenital abnormalities the effectiveness of treatment is achieved by surgical methods after specific chemotherapy. PMID- 1409506 TI - [Variants of the involution of pulmonary tuberculosis]. AB - The results of a many years' clinico-dispensary followup of 1597 patients with focal, infiltrative and disseminated tuberculosis and pulmonary tuberculomas were analysed. Current complex therapy of patients made it possible to distinguish 3 basic variants of the process involution: I--rapid resolution, II--at first rapid and then slow resolution and III-slow resolution. The main factor responsible for one or the other involution variant was a morphologic substrate of the process at the moment of its detection and primarily its recent character and the presence of extensive old specific background in the zone of a repeated outburst. The quality of treatment, including use of rifampicin, was of the decisive importance only in the presence of a recent process and the absence of such a background. Other factors including the patients' age, clinical form, phase and dissemination of the process were not crucial. Recent tuberculosis chemotherapy promoted the acceleration of reparative processes in the lung tissue in the presence of fresh changes. PMID- 1409507 TI - [Optimal effectiveness of complex treatment of patients with chronic obstructive bronchitis by intravascular laser irradiation of blood]. AB - Results of combined treatment of 100 patients with chronic obstructive bronchitis are presented in the paper. Intravascular laser irradiation of blood had a favourable effect on the clinical disease course, normalized parameters of lipid peroxidation, produced a marked immune stimulating and anti-inflammatory action, controlled the blood coagulation system and improved rheological blood properties. Intravascular laser irradiation of blood included in the complex of therapeutic measures increased the efficiency of therapy in patients with chronic obstructive bronchitis by 12.0 +/- 2.6%. PMID- 1409508 TI - [Possibilities of intravenous use of helium-neon laser in the treatment of experimental tuberculosis of animals]. AB - The study presents experimental finding of 40 mongrel dogs whose intravascular blood was irradiated with laser as a supplement to the multimodality treatment of respiratory tuberculosis. Earlier disappearance of intoxication symptoms and reduced terms of destruction cavity decrease and closure, as roentgenologically evidenced, was achieved. The influence of this treatment on certain lipid peroxidation parameters, hemocoagulation, immunity status and bacteriostatic blood activity were found. There were no side effects during treatment. PMID- 1409509 TI - [Antioxidant treatment of pulmonary tuberculosis in patients with chronic alcoholism]. AB - Study of the state of the antioxidant system (AOS) and lipid peroxidation (LPO), according to the data on the alpha-tocopherol content, diene conjugates and acid erythrocyte hemolysis in 69 patients suffering from pulmonary tuberculosis concurrent with chronic alcoholism, has revealed significant differences as against the findings related to healthy subjects (36), to those with stage 11 alcoholism (31) and pulmonary tuberculosis patients (51). Favourable changes in the AOS and LPO during complex treatment that includes antioxidant agents were less manifested in patients with combined pathology and appeared at later terms than in tuberculosis patients. The antioxidant therapy of tuberculosis in chronic alcoholics should take a prolonged time, at least 4 months, since the first favourable changes in the AOS and LPO parameters appear after 4 months, while normalization does not set in even after 6 months. PMID- 1409510 TI - [Combined chemotherapy of toxic hepatitis in patients with pulmonary tuberculosis]. AB - The follow-up involved patients with infiltrative pulmonary tuberculosis who developed toxic medicamentous hepatitis associated with antituberculosis drugs. They were treated by the method of combined pharmacotherapy which comprised sodium nucleinate (0.5 g 4 times daily), splenin (2 ml twice a day) and quercetin. The given combination of drugs rapidly improved clinical parameters and normalized immunologic tests. PMID- 1409511 TI - [Differential diagnosis of disseminated lesions of the lungs]. PMID- 1409512 TI - [Scintigraphic examination in the diagnosis of cavernous pulmonary tuberculosis]. PMID- 1409513 TI - [Tuberculous meningitis in BCG-vaccinated children]. PMID- 1409514 TI - [Functional morphology of the lungs in patients with tuberculosis and diabetes mellitus]. AB - The lungs of 20 patients (between the ages of 14 and 46 years) with tuberculosis and type I diabetes mellitus were subjected to a morphological examination with the help of a light and electron microscope. Thirteen patients were operated on for fibrous-cavernous tuberculosis and 7 for pulmonary tuberculoma. A duration of the concurrent diseases was 3 to 10 years (5.5 years, on average). All patients had a serious form of diabetes mellitus. The combined affection was characterized by a progressive course of tuberculosis with involvement of bronchi in the process. Specific features of tissue reactions pertinent to this combined pathology were revealed which comprised defective defense mechanisms (alveolar macrophages, type II alveolocytes and fibroblasts in the form of their dystrophy) generalized affection of pulmonary vessels, intensive fibre formation and disorganization of the forming connective tissue, which has a bearing on the development of the pathological process. PMID- 1409515 TI - [Population migration and tuberculosis]. AB - Characteristic features of a migratory process of tuberculosis patients in the Republic of Moldova were subjected to study. Two tendencies have been revealed: growth of a number of the arriving subjects and deterioration of the structure of pulmonary tuberculosis among them. Patients who arrived from the places of confinement where morbidity persists on a high level constitute a particular hazard concerning tuberculosis dissemination. Certain organization measures have been taken. The epidemiologic situation for tuberculosis in the penitentiary labour establishments at the republican Ministry of Internal Affairs was subjected to a comprehensive analysis with subsequent discussion of the results at a meeting of the staff of the Ministry of Public Health; instruction and plan of measures to be taken have been compiled by both ministries; a permanent board has been instituted for rendering help to medical workers of the penitentiary establishments; all law-protective organs have been involved in tuberculosis control; a specialized institution has been set up with a hospital for 200 beds intended for skilled examination and treatment of patients. As a result, the index of tuberculosis morbidity in the republican penitentiary-labour establishments reduced by more than half to promote an improvement of the epidemiologic situation in the republic. PMID- 1409516 TI - [Morphological characteristics of reparative processes in tuberculosis and the effect of pesticides]. AB - The paper deals with the results of a comparative morphologic, toxicologic and biochemical study of the character of reparative processes in destructive forms of pulmonary tuberculosis, specific features of non-coordination of collagen metabolism depending on the cumulation of organochlorine and organophosphorus pesticides and in the absence of their residual quantities in the patient's body on admission to a hospital and during current antibacterial therapy. The resected and removed lungs and blood of 1063 patients were used for the study. Specific features of a tuberculosis course, the duration and effectiveness of antibacterial therapy, the character of reparative processes, characteristic features of collagen metabolism and collagenosis, the character and dissemination of residual changes due to therapy were established in the compared groups of patients. PMID- 1409518 TI - [Indicators of iron metabolism in adolescents with tuberculosis]. AB - Iron metabolic parameters were studied in a sample of 25 adolescent patients with tuberculosis who had been followed up. ++Criteria were examined for assessing the data obtained which differ from those found in iron-deficiency anemia. A number of parameters (hemoglobin, total serum iron-binding capacity, erythrocytic ferritin) have been proposed, which should be considered in detecting iron deficiency anemia in a tuberculosis process. PMID- 1409517 TI - [Estimation of the degree of risk of reactivation of residual tuberculous changes based on the status of mycobacterial population]. AB - The study was undertaken to define the role of L-forms of M. tuberculosis having different qualitative and ++quantitative characteristics in the development of recurrences of a tuberculosis process in subjects with residual tuberculous changes in the lungs. The microbiological and ++clinico-roentgenological+ examination included 2412 subjects who were in VIIA and VIIB Dispensary Groups. These subjects were found to have a considerable reservoir of tuberculosis infection: the causative agent of tuberculosis in the bacterial and L-forms was detected in 214 (9%) of the examinees. Detection of M. tuberculosis L-forms tended to reversion in a pathological material of subjects with residual tuberculous changes in the lungs is a major predictors of high potential risk of tuberculosis process reactivation. PMID- 1409519 TI - [Analysis of the quality of clinical diagnosis based on autopsy data]. AB - The material is based on the autopsy findings collected over 15 years (1975 1989). Findings related to 748 fatal outcomes were subjected to analysis in which 90 (12%) cases were misdiagnosed regarding the principal disease. A percentage of diagnostic errors with respect to tuberculosis was 1.8 on the whole and in the diagnosis of clinical forms and phases it was considerably higher-15.9 and 19.4, respectively. Hyperdiagnosis was typical of disseminated tuberculosis and caseous pneumonia, while hypodiagnosis--of primary, fibrocavernous tuberculosis and post tuberculous changes. A percentage of hypodiagnosis in nontuberculous pathology varied from 12.5 to 50. Dynamic observation by the five-year plans demonstrated an increase in the percentage of misdiagnosis of the concurrent pathology and its decrease when the phase of a specific process was established. Purely medical errors accounted for 75% of misdiagnosis. PMID- 1409520 TI - [Screening of disorders of carbohydrate metabolism in patients with active pulmonary tuberculosis]. PMID- 1409521 TI - [Congestive abscess masking a soft tissue tumor]. PMID- 1409522 TI - [Meningoencephalitis as a cause of death of children with tuberculosis]. PMID- 1409523 TI - [Chronic bronchitis--the most frequent clinical variant of extrinsic allergic alveolitis in furniture factory workers]. PMID- 1409524 TI - [An optimal method of pharmacological prevention of tuberculosis among adolescents]. AB - The paper presents the findings of a comparative study of the efficacy of chemoprophylaxis which was conducted by the everyday (1 course) and intermittent (2 courses) method in adolescents aged 12-17 years, depending on the presence of aggravating factors. Examination covered 150 adolescents from the VI registration group. Following chemoprophylaxis there was a drop in sensitivity to tuberculin in 95.5 +/- 0.8% of group 1 (main) and in 78.5 +/- 1.1% of group 2 cases during which a medium size of an infiltrate in group 1 reduced by 2.8 mm more than that in group 2 (p less than 0.001). After the end of an observation period, 92.4 +/- 0.8% of subjects of group 1 and 79.4 +/- 0.5% of subjects of group 2 were struck off the register from the VIA registration group; the respective figures for the VIB registration group were 73.2 +/- 0.2% and 58.6 +/- 3%. The epidemiologic and economic effect of chemoprophylaxis conducted by 2 courses was 2 and 1.5 times higher than that in the traditional method. PMID- 1409525 TI - [Effectiveness of BCG vaccination in children in relation to genetic and social factors]. AB - The social status, genetic parameters, somatic and infectious diseases have been studied in BCG--vaccinated children who presented a postvaccinal cicatrix and in those in whom it did not form. Children having a postvaccinal cicatrix were found to belong mainly to the muscular type of constitution, while those without it--to the thoracic type. It was shown that a one--time positive tuberculin reaction to the Mantoux test with 2 TU (infiltrate of 6-7 mm) is associated with somatic and infectious pathology. This reaction can be considered to be para--allergy within 4 months after the disease. PMID- 1409526 TI - Inhibitory effect of Trypanosoma brucei brucei on Glossina morsitans midgut trypsin in vitro. AB - The ability of Trypanosoma brucei brucei to inhibit trypsin or trypsin-like enzymes in crude midgut homogenates of Glossina morsitans morsitans was studied in vitro. The isolated parasites caused a concentration-dependent decrease in midgut trypsin activity. Furthermore, trypanosomes lysed by repeated freeze thawing had a similar effect on trypsin activity. In both cases, the inhibition by either intact or lysed parasites was partial as revealed by Dixon plots. Similarly, trypanosome membrane proteins stoichiometrically inhibited trypsin activity, suggesting that the enzyme interacts specifically with a moiety on the parasite surface. The Km and Ki values obtained in this case were 35 microM and 0.18 mg/ml, respectively. These results suggest that one of the ways in which trypanosomes overcome the hostile tsetse-fly midgut barrier involves the inhibition of enzyme activity. PMID- 1409527 TI - Effect of buparvaquone on the expression of interleukin 2 receptors in Theileria annulata-infected cells. AB - Theileria annulata-infected cells were cultured in the presence or absence of human recombinant interleukin 2 (hrIL-2). This growth factor proved to be capable of enhancing the growth of the infected cells: its effect was marked, particularly when the cells were seeded at low densities, and it varied from cell line to cell line. The infected cells produced a factor that possessed the biological activities of IL-2, since their supernatants could enhance the proliferation of concanvalin A-stimulated (Con A) blasts. The reactivity of the parasitized cells to hrIL-2 was abolished following their treatment with the antitheilerial drug buparvaquone. In addition, the drug inhibited the binding of 125I-IL-2 to T. annulata-infected cells but failed to suppress its binding to Con A blasts. Northern blot analysis revealed that the drug had no effect on the expression of the alpha chain of the IL-2 receptor (IL-2R). Therefore, it is possible that buparvaquone interferes with the expression of the beta chain of the IL-2R. The role of IL-2 and the IL2R in the permanent proliferation of T. annulata-infected cells is discussed. PMID- 1409528 TI - Echinococcus multilocularis: immunological study on the "Em2-positive" laminated layer during in vitro and in vivo post-oncospheral and larval development. AB - Echinococcus multilocularis oncospheres, primary vesicular cysts, and protoscolices were assessed in vitro and in vivo for their potential to synthesize a PAS-positive laminated layer containing monoclonal antibody (mAb) G11-binding Em2 antigen. The presence of Em2 antigen in developed oncospheres and cysts was subsequently correlated to the potential of in vivo development into a secondary metacestode in recipient host mice, which also responded by anti-Em2 serum antibody formation. In contrast, protoscolices failed to develop the "Em2 positive" layer in vitro under the selected experimental conditions. The failure to develop subsequently in vivo into a secondary metacestode was underlined by a lack of anti-Em2 serum antibody formation by the hosts. We furthermore developed a technique to obtain E. multilocularis clones by inoculating single oncospheres into recipient mice. PMID- 1409529 TI - Use of a recombinant Dictyocaulus viviparus antigen in an enzyme-linked immunosorbent assay for immunodiagnosis of bovine dictyocaulosis. AB - A specific recombinant antigen was evaluated for its immunodiagnostic potential in an enzyme-linked immunosorbent assay (ELISA). The antigen was used as a glutathione S-transferase (GST) fusion protein (DvGST3-14) or as a pure recombinant parasite protein (Dv3-14). A total of 55 sera from cattle experimentally infected with Dictyocaulus viviparus, 24 sera from naturally infected cattle and 25 sera from helminth-free cattle were examined. ELISA results obtained for the sera from experimental infections showed a calculated specificity of greater than 99% for both antigen preparations and a sensitivity of 93% (DvGST3-14) and 91% (Dv3-14). For field sera from natural infections, the specificity was calculated to be 90% (DvGST3-14) and greater than 99% (Dv3-14) and the sensitivity, 85% (DvGST3-14) and 70% (Dv3-14). PMID- 1409531 TI - Neoglycoproteins as tools for the detection of carbohydrate-specific receptors on the cell surface of Leishmania. AB - Promastigote and amastigote forms of human pathogenic Leishmania from the Old and New World, including promastigotes of L. enrietti, were tested with neoglycoproteins to ascertain the existence of endogenous lectins. These tools expose the chemically coupled sugar that is attached to the inert carrier as a potential ligand for the binding reaction. Agglutination tests demonstrated that the promastigotes of human Leishmania reacted only with the neoglycoproteins N acetyl-D-galactosamine-para-aminophenyl-bovine serum albumin (gal-NAc-BSA) and N acetyl-D-glucosamine-para-amino-phenyl-bovine serum albumin (glcNAc-BSA), whereas the amastigote forms failed to react with the neoglycoproteins. In contrast, the promastigotes of L. enriettii were agglutinated by the neoglycoprotein D-mannose bovine serum albumin (man-BSA). The agglutination reactions could be inhibited by the homologous sugars N-acetyl-beta-D-glucosamine, N-acetyl-beta-D-galactosamine, and alpha-D-mannose. Fluorescence tests yielded the same results. The incubation of the promastigotes with ethylenedinitrolotetraacetic acid (EDTA) prevented their reaction with the neoglycoproteins, whereas the addition of calcium restored it. This result demonstrates that Leishmania express calcium-dependent lectins that are accessible on their surface. PMID- 1409530 TI - Detection of Echinococcus coproantigens by enzyme-linked immunosorbent assay in dogs, dingoes and foxes. AB - An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of Echinococcus coproantigens in fecal samples from dogs, dingoes or foxes infected with either E. granulosus or E. multilocularis. The ELISA was based on protein-A purified polyclonal antibodies [anti-E. granulosus excretory/secretory (E/S) antigens]. The specificity of the assay as determined in 155 samples derived from carnivores that were free of helminth infection (n = 37) or infected with non Echinococcus cestodes (n = 76) or with various nematodes (n = 42) was found to be 98% overall. The diagnostic sensitivity was strongly dependent on the homologous worm burden. All 13 samples from foxes harboring greater than 1,000 E. multilocularis worms and 13 of 15 (87%) samples from dogs or dingoes containing greater than 200 E. granulosus worms were ELISA-positive, whereas 34 of 46 samples from foxes harboring less than 1,000 E. multilocularis and 9 of 10 samples from dogs or dingoes bearing less than 200 E. granulosus tested negative. Experimental prepatent infections of dogs with E. granulosus revealed positive ELISA reactions within the prepatent period (10-20 days post-infection) for six animals bearing greater than 1,000 E. granulosus each; a low worm burden (less than 1,000 tapeworms/animal) resulted in ELISA positivity in only 2 of 3 animals at 30 days post-infection at the earliest. All five dogs that had been experimentally infected with E. multilocularis tested positive in the coproantigen ELISA as early as on day 5 post-infection. PMID- 1409532 TI - Cellular responses to culture-derived soluble exoantigens of Trypanosoma lewisi. AB - Soluble exoantigens of Trypanosoma lewisi were obtained from short-culture systems of dividing epimastigotes and non-dividing trypomastigotes incubated in phosphate-buffered saline glucose solution (PBSG) for 3 h at 37 degrees C. Suppression of normal rat-spleen cell responses to mitogen concanavalin A (Con A) occurred at high exoantigens concentrations. The epimastigote-derived exoantigens were more suppressive than the trypomastigote-derived exoantigens. The suppression of Con A stimulation was ablated by the addition of exogenous interleukin-2 (IL-2) or washing of spleen cells that had been incubated with suppressing concentrations of the epimastigote exoantigens for 24 h prior to Con A stimulation. These results strongly suggest that exoantigens of T. lewisi play an important immunoregulatory role during the course of infection and that they achieve this by inhibiting the production of IL-2 by T-helper cells. PMID- 1409533 TI - Immunoreactivity to two specific regions of chromogranin A in the nervous system of Ascaris suum: an immunocytochemical study. AB - Antisera to a highly conserved region of chromogranin A (sequence KELTAE) and to a hexapeptide (sequence KGQELE) adjacent to the putative C-terminus of pancreastatin, a peptide whose sequence is found within the chromogranin A molecule, have been used to examine the localisation of immunoreactivity (IR) to these peptides in Ascaris suum. IR to both peptides was found in the nerve rings and nerve cords. In addition, KGQELE-IR was also observed in the pharyngeal neurones and in a network of fibres on the surface of the female gonoduct. The staining was specific in that it could be abolished by preincubation of the antisera with the appropriate antigen. The two antisera appeared to be staining different subsets of neurones, suggesting that (at least) two peptides were being recognised. The wide-spread distribution of IR to both peptides throughout the nervous system of the parasite suggests that the peptides carrying the epitopes recognised by the antisera are of fundamental importance to the functioning of the parasite's nervous system. PMID- 1409534 TI - Adherence between Entamoeba histolytica trophozoites and undifferentiated or DMSO induced HL-60 cells. AB - Differentiation of promyelocytic HL-60 cells along the pathway toward granulocytes using dimethyl-sulfoxide (DMSO) led to increased expression of the adhesion molecules CD11b (Mac-1), CD11c (p150,95), and CD35 (CR1). Undifferentiated and differentiated HL-60 cells adhered similarly to Entamoeba histolytica trophozoites, and monoclonal antibodies against adhesion molecules CD11b and CD11c did not inhibit adherence. We therefore suggest that CD11b and CD11c are not involved in the adherence between polymorphonuclear granulocytes and E. histolytica trophozoites. PMID- 1409535 TI - Distribution of a fluorescent ivermectin probe, bodipy ivermectin, in tissues of the nematode parasite Ascaris suum. AB - A fluorescent derivative of the anthelmintic ivermectin (4''-5,7-dimethyl bodipy proprionylivermectin, referred to hereafter as bodipy ivermectin) was synthesized for an investigation of the distribution of avermectins. Injected into adult Ascaris suum at doses greater than 0.1 micron per worm, it produced a dose dependent immobilization. Fluorescent microscopy of frozen sections revealed the distribution of the probe in the whole nematode. Staining of collagenase-isolated muscle cells was studied using bath application of bodipy ivermectin. The trypan blue quenching technique showed that the ivermectin probe was located in the outer monolayer of the muscle membrane. The cytoplasm was not stained. The interpretation of these observations is discussed in view of the known lipophilic nature of avermectins. Staining of the muscle membrane and nerve cord is consistent with the view that avermectins act at these sites. The significance of the hypodermal and lateral line staining is also discussed. PMID- 1409536 TI - In vitro effects of milbemycin oxime: mechanism of action against Angiostrongylus cantonensis and Dirofilaria immitis. AB - The neuropharmacological mechanisms underlying the action of milbemycin oxime on the motility of Angiostrongylus cantonensis and Dirofilaria immitis were examined in vitro. In A. cantonensis, milbemycin oxime caused inhibitory effects at low concentrations of > or = 10(-9) g/ml, and paralysis was elicited at 10(-8) - 10( 6) g/ml. The paralysis was antagonized by picrotoxin and bicuculline but not by dibenamine. In addition, stimulatory effects were observed when the antibiotic was used at higher concentrations of 3-5 x 10(-6) g/ml, and the action was antagonized by strychnine. Both effects were also observed in the preparation contracted by eserine or pyrantel. When D. immitis was treated with milbemycin oxime at concentrations of 10(-7) and 3-5 x 10(-6) g/ml, only slight inhibitory and stimulatory effects, respectively, were observed. These effects were partially antagonized by picrotoxin and strychnine, respectively. These results suggest that the inhibitory and stimulatory actions of milbemycin oxime are caused through gabergic and cholinergic mechanisms in A. cantonensis and D. immitis. PMID- 1409537 TI - Fasciola hepatica: early lesions in the viscera of seven pulmonate species after penetration of the miracidium. AB - Early lesions were studied in four viscera of seven pulmonate species on the 2nd day after miracidial exposure. The albumen gland, the digestive gland, and the gonad of infected snails demonstrated not only normal tissue but also the presence of two stages of epithelial necrosis. Multifocal necrosis predominated, with varying percentages of frequency depending on the snail species and stage of life; generalized necrosis was more seldom observed. In the kidney, epithelial necrosis was encountered more frequently than intralamellar deposits. PMID- 1409538 TI - Quantitative analysis of protein far UV circular dichroism spectra by neural networks. AB - A new method based on neural network theory is presented to analyze and quantify the information content of far UV circular dichroism spectra. Using a backpropagation network model with a single hidden layer between input and output, it was possible to deduce five different secondary structure fractions (helix, parallel and antiparallel beta-sheet, beta-turn and random coil) with satisfactory correlations between calculated and measured secondary structure data. We demonstrate that for each wavelength interval a specific network is suitable. The remaining discrepancy between the secondary structure data from neural network prediction and crystallography may be attributed to errors in the determination of protein concentration and random noise in the CD signal, as indicated by simulations. PMID- 1409539 TI - The alpha/beta hydrolase fold. AB - We have identified a new protein fold--the alpha/beta hydrolase fold--that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta sheet, not barrel, of eight beta-sheets connected by alpha-helices. These enzymes have diverged from a common ancestor so as to preserve the arrangement of the catalytic residues, not the binding site. They all have a catalytic triad, the elements of which are borne on loops which are the best-conserved structural features in the fold. Only the histidine in the nucleophile-histidine-acid catalytic triad is completely conserved, with the nucleophile and acid loops accommodating more than one type of amino acid. The unique topological and sequence arrangement of the triad residues produces a catalytic triad which is, in a sense, a mirror-image of the serine protease catalytic triad. There are now four groups of enzymes which contain catalytic triads and which are related by convergent evolution towards a stable, useful active site: the eukaryotic serine proteases, the cysteine proteases, subtilisins and the alpha/beta hydrolase fold enzymes. PMID- 1409540 TI - The functions of tryptophan residues in membrane proteins. AB - Membrane proteins have a significantly higher Trp content than do soluble proteins. This is especially true for the M and L subunits of the photosynthetic reaction center from purple bacteria. The Trp residues are not uniformly distributed through the membrane but are concentrated at the periplasmic side of the complex. In addition, Trp residues are not randomly aligned. Within the protein subunits, many form hydrogen bonds with carbonyl oxygens of the main chain, thereby stabilizing the protein. On the surface of the molecule, they are correctly positioned to form hydrogen bonds with the lipid head groups while their hydrophobic rings are immersed in the lipid part of the bilayer. These observations suggest that Trp residues are involved in the translocation of protein through the membrane and that following translocation, Trp residues serve as anchors on the periplasmic side of the membrane. PMID- 1409541 TI - Calculations of antibody-antigen interactions: microscopic and semi-microscopic evaluation of the free energies of binding of phosphorylcholine analogs to McPC603. AB - The study of antibody-antigen interactions should greatly benefit from the development of quantitative models for the evaluation of binding free energies in proteins. The present work addresses this challenge by considering the test case of the binding free energies of phosphorylcholine analogs to the murine myeloma protein McPC603. This includes the evaluation of the differential binding energy as well as the absolute binding energies and their corresponding electrostatic contributions. Four different approaches are examined: the Protein Dipoles Langevin Dipoles (PDLD) method, the semi-microscopic PDLD (PDLD/S) method, a free energy perturbation (FEP) method based on an adiabatic charging procedure and a linear response approximation that accelerates the FEP calculation. The PDLD electrostatic calculations are augmented by estimates of the relevant hydrophobic and steric contributions. The determination of the hydrophobic energy involves an approach which considers the modification of the effective surface area of the solute by local field effects. The steric contributions are analyzed in terms of the corresponding reorganization energies. This treatment, which considers the protein as a harmonic system, views the steric forces as the restoring forces for the electrostatic interactions. The FEP method is found to give unreliable results with regular cut-off radii and starts to give quantitative results only in very expensive treatment with very large cut-off radii. The PDLD and PDLD/S methods are much faster than the FEP approach and give reasonable results for both the relative and absolute binding energies. The speed and simplicity of the PDLD/S method make it an effective strategy for interactive docking studies and indeed such an option is incorporated in the program MOLARIS. A component analysis of the different energy contributions of the FEP treatment and a similar PDLD analysis indicate that electrostatic effects provide the largest contribution to the differential binding energy, while the hydrophobic and steric contributions are much smaller. This finding lends further support to the idea that electrostatic interactions play a major role in determining the antigen specificity of McPC603. PMID- 1409542 TI - A functional antibody mutant with an insertion in the framework region 3 loop of the VH domain: implications for antibody engineering. AB - We have studied the effects of a four residue insertion into the FR3 loop of the heavy chain variable region from the anti-NP antibody B1-8. The insertion mutant is obtained as secreted antibody without major defects in biosynthesis, indicating that antibody variable domains can accommodate length variation not only in complementarity determining regions (CDRs), but also in framework region (FR) loops. The B1-8 antigen binding site is not affected by the change in a neighbouring loop. FR3 insertions represent a new method of antibody engineering with a potential to obtain strong antigen binding by designing additional antigen contacting residues. PMID- 1409543 TI - Fluorescent properties of the Escherichia coli D-xylose isomerase active site. AB - The consequences of active site mutations of the Escherichia coli D-xylose isomerase (E.C. 5.3.1.5) on substrate binding were examined by fluorescence spectroscopy. Site-directed mutagenesis of conserved tryptophan residues in the E. coli enzyme (Trp49 and Trp188) reveals that fluorescence quenching of these residues occurs during the binding of xylose by the wild-type enzyme. The fluorescent properties of additional active site substitutions at His101 were also examined. Substitutions of His101 which inactivate the enzyme were shown to have altered spectral characteristics, which preclude detection of substrate binding. In the case of H101S, a mutant protein with measurable isomerizing activity, substrate binding with novel fluorescent properties was observed, possibly the bound pyranose form of xylose under steady-state conditions. PMID- 1409544 TI - Phe496 and Leu497 are essential for receptor binding and cytotoxic action of the murine interleukin-4 receptor targeted fusion toxin DAB389-mIL-4. AB - DAB389-mIL-4 is a murine interleukin-4 (mIL-4) diphtheria toxin-related fusion protein which has been shown to be selectively toxic to cells expressing the mIL 4 receptor. In this report, we have used site-directed and in-frame deletion mutagenesis to study the role of the putative C-terminal alpha-helix (helix E) of the mIL-4 component of DAB389-mIL-4 in the intoxication process. We demonstrate that deletion of the C-terminal 15 amino acids of the fusion toxin leads to loss of cytotoxicity. The substitution of Phe496 with either Pro, Ala or Tyr, results in a greater than 20-fold decrease in cytotoxic activity of the respective mutant fusion toxins. In addition, substitution of Leu497 with either Ala or Glu results in a similar loss of cytotoxic activity. All of these mutant forms of the mIL-4 fusion toxin demonstrate a significant decrease in binding affinity (Ki) to the mIL-4 receptor in a competitive radioligand binding assay. In marked contrast, however, the substitution of Asp495 with Asn results in a 4-fold increase in cytotoxic potency and binding affinity to mIL-4 receptor bearing cells in vitro. PMID- 1409545 TI - A point mutation that decreases the thermal stability of human interferon gamma. AB - We have identified a mutation of human gamma-interferon (IFN gamma) causing a temperature-sensitive phenotype. We used a randomized oligonucleotide to mutagenize a synthetic human IFN gamma gene, then screened the resulting mutants produced in Escherichia coli for proteins with altered biological activity. One mutant protein selected for detailed characterization exhibited less than 0.3% of the specific biological activity of native IFN gamma in an antiviral activity assay performed at 37 degrees C. However, the protein bound the human IFN gamma receptor with native efficiency at 4 degrees C. Sequencing the plasmid DNA encoding this protein showed that the mutation changed the lysine residue at amino acid 43 to glutamic acid (IFN gamma/K43E). Site-specific mutagenesis at amino acid 43 showed that this protein's phenotype resulted from positioning a negative charge at position 43. Structural characterization of IFN gamma/K43E using CD demonstrated that the protein had native conformation at 25 degrees C, but assumed an altered conformation at 37 degrees C. IFN gamma/K43E in this altered conformation bound poorly to the IFN gamma receptor at 37 degrees C, providing a rationale for the mutant's decreased antiviral activity. PMID- 1409546 TI - A point mutation of human interferon gamma abolishes receptor recognition. AB - We identified a single amino acid mutation that abolished the bioactivity of human IFN gamma. The mutation was identified by screening a mutagenized IFN gamma expression library for molecules with altered biological activity. The mutant protein was expressed at high levels in Escherichia coli, and remained soluble upon purification. However, the protein was completely inactive in all IFN gamma assays investigated, exhibiting less than 0.0006% of the specific activity of native IFN gamma antiviral activity. Sequencing the plasmid DNA encoding this mutant protein showed that the histidine at position 111 of native human IFN gamma is changed to aspartic acid (IFN gamma/H111D). Other mutations at this site showed that only hydrophobic amino acids at position 111 maintain significant, though low, biological activity. Structural characterization of the IFN gamma/H111D protein by NMR as well as CD spectroscopy demonstrated that the protein has limited conformational differences from native IFN gamma. Models of the X-ray crystal structure of human IFN gamma [Ealick, P.E., W.J. Cook, S. Vijay Kumar, M. Carson, T.L. Nagabhushan, P.P. Trotta and C.E. Bugg (1991) Science, 252, 698-702] suggest that this histidine residue is located at a severe 55 degrees bend in the C-terminal F helix. We conclude that H111 lies within or affects the receptor binding domain of human IFN gamma. PMID- 1409547 TI - Involvement of residues 296-299 in the enzymatic activity of tissue-type plasminogen activator. AB - The tetra-alanine substitution variant KHRR 296-299 AAAA of tissue-type plasminogen activator (t-PA) was previously shown to have enhanced fibrin specificity and enhanced activity in the presence of fibrin compared with the wild-type form of the molecule. The structural requirements for these alterations in enzymatic activity were investigated by constructing several amino acid substitution variants at each of the positions from 296 to 299 and evaluating their activities under a variety of conditions. Effects on plasminogen activator activity were common among the point mutants at positions 296-299; nearly all had a phenotype similar to the KHRR 296-299 AAAA variant. The greatest effects on enzymatic function were found with multiple substitution variants, but some single charge reversals and proline substitutions had substantial effects. The enhanced fibrin specificity of KHRR 296-299 AAAA t-PA results in less fibrinogenolysis than seen with wild-type t-PA. Approximately four times greater concentration of KHRR 296-299 AAAA compared with wild-type t-PA was required to consume 50% of the fibrinogen in human plasma. PMID- 1409548 TI - A new protein conjugate that replaces the use of secondary antibodies engineered from the two staphylococcal enzymes protein A and 6-phospho-beta-galactosidase. AB - The lacG gene encoding the 6-phospho-beta-galactosidase (E.C.3.2.1.85) of Staphylococcus aureus was fused to the protein A gene in the plasmid pRIT2T. Escherichia coli cells containing this plasmid produce a fusion protein with both IgG binding and 6-phospho-beta-galactosidase activities after heat induction. The recombinant gene was overexpressed and the hybrid protein was purified to homogeneity in high yield. The chimeric protein was shown to have almost identical enzymatic characteristics to pure 6-phospho-beta-galactosidase. This result leads to the conclusion that a free N-terminus of the 6-phospho-beta galactosidase is not required for biological activity. The hybrid protein of protein A and 6-phospho-beta-galactosidase was used as an enzyme conjugate in enzyme-linked immunosorbent assays (ELISA). The experiments presented demonstrate that the 6-phospho-beta-galactosidase is a suitable fusion partner in various diagnostic applications where an unique biological activity is required. PMID- 1409549 TI - Insertion of a disulfide-containing neurotoxin into E. coli alkaline phosphatase: the hybrid retains both biological activities. AB - We have inserted a disulfide-containing snake neurotoxin into the N-terminal end of Escherichia coli alkaline phosphatase, between residues +6 and +7 of the mature enzyme. For this purpose, we have designed a cloning and expression vector which allows insertion of foreign DNA between the corresponding codons, and visual selection of the desired recombinant clones upon recovery of phosphatase activity. The hybrid protein is exported to the bacterial periplasm, the alkaline phosphatase signal peptide is correctly processed, and both domains are functionally conformed. The phosphatase domain displays catalytic activity, and the inserted toxin is able to bind to its biological target, the nicotinic acetylcholine receptor. The hybrid molecule is remarkably stable and resistant to proteolysis. Crude periplasmic extract containing the hybrid can be used as a tracer-containing reagent in competitive enzymo-immuno and enzymo-receptor assays. We propose to use the system described in this paper for fast preparation of properly folded disulfide-containing enzymatic probes. PMID- 1409550 TI - An SS1-SS2 beta-barrel structure for the voltage-activated potassium channel. AB - To examine the feasibility of a beta structure for the pore-lining region of the voltage-gated potassium channel, we have characterized a family of 12 antiparallel beta-barrels. Each is comprised of four identical pairs of beta strands organized with approximate 4-fold symmetry about a channel axis. The C- and N-termini of the beta-strand pairs are assumed to be at the extracellular end of the channel, and each pair is connected by a hairpin turn at the intracellular end of the channel. The models differ in the residues located in the hairpin turn and in the orientation of the two strands of each pair in the barrel, i.e. whether the C-terminus of a pair is clockwise (CW) or counterclockwise (CCW) from the N-terminus when the channel is viewed from outside the cell. Following known structure precedents and potential energy predictions, the barrel is assumed to be right-twisting in all cases. All models have crowded layers of inward projecting aromatic side-chains near the center of the channel which could regulate channel selectivity. The models with an odd number of amino acids in the hairpin turn have the advantage of predicting that F433 points into the barrel, but the disadvantage that V438 does not. Of these models, two of the models are most consistent with the external tetraethylammonium (TEA) block data, and of those, one (T439 CCW 3:5) is most consistent with the internal TEA block data. PMID- 1409551 TI - Main structural and functional features of the basic cytosolic bovine 21 kDa protein delineated through hydrophobic cluster analysis and molecular modelling. AB - A 21 kDa protein purified from bovine brain cytosol was previously described as a hydrophobic ligand binding protein; however, its accurate biological function remained still uncertain. In order to get further information about its potential biological role, an extended prediction of its secondary and three dimensional structures was undertaken. We describe here a process which permitted us to discover a structural homology between the 21 kDa protein and the N-domain of yeast phosphoglycerate kinase (PGK). This process is based on comparing the 21 kDa protein with all the proteins presenting a slight homology, by using the Hydrophobic Cluster Analysis (HCA) method. According to the observed similarity between the N-domain of yeast PGK and the 21 kDa protein, we built a model which was shown to possess a potential binding site for nucleotides. Moreover, the model obtained presents three-dimensional (3D) structure similarity with adenylate kinase. These results suggest two main hypotheses: (i) the 21 kDa protein may belong to the kinase family; (ii) the binding of a nucleotide could imply a modification of the 3D structure of the 21 kDa protein that can promote the transfer of hydrophobic ligands to the plasma membrane. Meanwhile, verification of these hypotheses has been in part performed experimentally: the 21 kDa protein binds MgATP as well as, to a lesser extent, phosphoglycerate. PMID- 1409552 TI - Towards an automatic method of predicting protein structure by homology: an evaluation of suboptimal sequence alignments. AB - A major problem in predicting protein structure by homology modelling is that the sequence alignment from which the model is built may not be the best one in terms of the correct equivalencing of residues assessed by structural or functional criteria. A useful strategy is to generate and examine a number of suboptimal alignments as better alignments can often be found away from the optimal. A procedure to filter rapidly suboptimal alignments based on measurement of core volumes and packing pair potentials is investigated. The approach is benchmarked on three pairs of sequences which are non-trivial to align correctly, namely two immunoglobulin domains, plastocyanin with azurin and two distant globin sequences. It is shown to be useful to reduce a large ensemble of possible alignments down to a few which correspond more closely to the correct (structure based) alignment. PMID- 1409553 TI - Computational complexity of a problem in molecular structure prediction. AB - The computational task of protein structure prediction is believed to require exponential time, but previous arguments as to its intractability have taken into account only the size of a protein's conformational space. Such arguments do not rule out the possible existence of an algorithm, more selective than exhaustive search, that is efficient and exact. (An efficient algorithm is one that is guaranteed, for all possible inputs, to run in time bounded by a function polynomial in the problem size. An intractable problem is one for which no efficient algorithm exists.) Questions regarding the possible intractability of problems are often best answered using the theory of NP-completeness. In this treatment we show the NP-hardness of two typical mathematical statements of empirical potential energy function minimization of macromolecules. Unless all NP complete problems can be solved efficiently, these results imply that a function minimization algorithm can be efficient for protein structure prediction only if it exploits protein-specific properties that prohibit the simple geometric constructions that we use in our proofs. Analysis of further mathematical statements of molecular structure prediction could constitute a systematic methodology for identifying sources of complexity in protein folding, and for guiding development of predictive algorithms. PMID- 1409554 TI - Design, synthesis and structure of an amphipathic peptide with pH-inducible haemolytic activity. AB - A synthetic, 26-residue peptide having a strong helix forming potential in the protonated state was designed to interact with lipid bilayers in a pH-dependent way. On the basis of this concept a cluster of four glutamic acid residues was inserted in the central region of the amphipathic peptide to promote helix destabilization by mutual charge repulsion at neutral pH. Protonation of these residues might then bring about both a pH-mediated change in hydrophobicity and conformation forming a membrane-active amphiphilic helix. The sequence GLGTLLTLLEFLLEELLEFLKRKRQQamide produced by the design strategy induced pH triggered lysis of human erythrocytes. A molecular model correlating the lytic activity to the formation of transmembrane pores which were detected by electron microscopy in erythrocyte membranes is discussed. Circular dichroism studies indicated a self-association of the monomeric random coil form with increasing peptide concentration leading to the apparent induction of strong alpha-helix formation (approximately 100% helicity) in the fully aggregated state. However, no pH-dependent helix-random coil transition was observed, implying that interhelical hydrophobic and ionic interactions not only govern the self association but also decisively influence the conformational stability of the peptide. PMID- 1409555 TI - Molecular modelling and site-directed mutagenesis on a bovine anti-testosterone monoclonal antibody. AB - A three-dimensional (3D) molecular model of the antigen-combining site of a bovine anti-testosterone monoclonal antibody has been constructed. In the model, the CDRs, and a single heavy chain framework region residue (Trp47), associate to form a hydrophobic cavity large enough to accommodate a single molecule of testosterone. Tyr97 of CDR-H3 lies at the bottom of the cavity with its hydroxyl group exposed to solvent. Using the model and data from binding studies, we predicted that the cavity forms the antibody's paratope and on binding testosterone a hydrogen bond is formed between Tyr97 of CDR-H3 and the hydroxyl group on the D-ring of testosterone. This prediction has subsequently been tested by site-directed mutagenesis. An antibody with phenylalanine in place of tyrosine at position 97 in CDR-H3 has its affinity reduced by approximately 800 fold. The reduction in binding energy associated with the reduced affinity has been calculated to be 3.9 kcal/mol which is within the range (0.5-4.0 kcal/mol) expected for the loss of a single hydrogen bond. The model has been used to suggest ways of increasing the antibody's affinity for testosterone. PMID- 1409556 TI - Interchain cysteine bridges control entry of progesterone to the central cavity of the uteroglobin dimer. AB - The progesterone-binding protein uteroglobin has been expressed in Escherichia coli in an unfused, soluble form. Like mature uteroglobin from rabbit endometrium (UG), the E.coli produced uteroglobin (UG1) dimerizes in vitro, forms an antiparallel dimer with Cys3-Cys69' and Cys69-Cys3' disulfide bonds and binds progesterone under reducing conditions. In order to analyze the dimerization and the reduction dependence of progesterone binding in more detail, we separately replaced cysteine 3 and cysteine 69 by serines. Under reducing conditions, both uteroglobin variants (UG1-3Ser and UG1-69Ser) bind progesterone with the same affinity as the wild-type suggesting that both cysteine residues are not directly involved in progesterone binding. In contrast to the wild-type protein, both cysteine variants also bind progesterone with high affinity in the absence of reducing agents. In addition, UG1-3Ser and UG1-69Ser both form covalently linked homodimers. Thus, unnatural Cys69-69' and Cys3-3' disulfide bonds exist in UG1 3Ser and UG1-69Ser, respectively. These data together with computer models based on X-ray diffraction data strongly support the idea that progesterone reaches its binding site located in an internal hydrophobic cavity via a hydrophobic tunnel along helices 1 and 4. Under non-reducing conditions the tunnel is closed by two disulfide bridges (Cys3-Cys69' and Cys69-Cys3') that lie in the most flexible region of the dimer. Reduction or replacement of a cysteine residue enables conformational changes that open the channel allowing progesterone to enter. PMID- 1409557 TI - Cellulose-binding domains: potential for purification of complex proteins. AB - The endoglucanase CenA and the exoglucanase Cex from Cellulomonas fimi each contain a discrete cellulose-binding domain (CBD), at the amino-terminus or carboxyl-terminus respectively. The gene fragment encoding the CBD can be fused to the gene of a protein of interest. Using this approach hybrid proteins can be engineered which bind reversibly to cellulose and exhibit the biological activity of the protein partner. Alkaline phosphatase (PhoA) from Escherichia coli, and a beta-glucosidase (Abg) from an Agrobacterium sp. are dimeric proteins. The fusion polypeptides CenA-PhoA and Abg-CBC(Cex) are sensitive to proteolysis at the junctions between the fusion partners. Proteolysis results in a mixture of homo- and heterodimers; these bind to cellulose if one or both of the monomers carry a CBD, e.g. CenA-PhoA/CenA-PhoA and CenA-PhoA/PhoA. CBD fusion polypeptides could be used in this way to purify polypeptides which associate with the fusion partner. PMID- 1409558 TI - Expression of a synthetic gene coding for the amino acid sequence of Clostridium pasteurianum rubredoxin. AB - A synthetic gene based on the published amino acid sequence for Clostridium pasteurianum rubredoxin was constructed, cloned in Escherichia coli 71/18 and expressed using the T7 RNA polymerase/promoter system in E. coli HMS273. UV/visible spectroscopy and metal analyses indicated that the as-isolated synthetic gene product is a mixture of holo-(i.e. iron-containing) rubredoxin and zinc-substituted rubredoxin, with the latter amounting to approximately 70% of the total rubredoxin. The UV/visible absorption and resonance Raman spectra of the cloned holorubredoxin are characteristic of the native rubredoxin-type iron site. N-terminal amino acid sequencing suggests that the gene product consists of at least three polypeptide species with the initial sequences (approximate relative abundances): Met-Met-Lys-... (63%), blocked (30%) and Met-Lys-... (7%). The blocked portion presumably consists of a mixture of nMet-Met-Lys-... and nMet Lys-..., where nMet represents an amino-blocked methionine residue. PMID- 1409559 TI - Monte Carlo minimization with thermalization for global optimization of polypeptide conformations in cartesian coordinate space. AB - A new minimization procedure for the global optimization in cartesian coordinate space of the conformational energy of a polypeptide chain is presented. The Metropolis Monte Carlo minimization is thereby supplemented by a thermalization process, which is initiated whenever a structure becomes trapped in an area containing closely located local minima in the conformational space. The method has been applied to the endogenous opioid pentapeptide methionine enkephalin. Five among 13 different starting conformations led to the same apparent global minimum of an in-house developed energy function, a type II' reverse turn, the central residues of which are Gly-3-Phe-4. A comparison between the ECEPP/2 global minimum conformation of methionine enkephalin and the apparent one achieved by the present method shows that minimum-energy conformations having a certain similarity can be generated by relatively different force fields. PMID- 1409560 TI - Overproduction, crystallization, and preliminary X-ray diffraction studies of the major cold shock protein from Bacillus subtilis, CspB. AB - The major cold shock protein from Bacillus subtilis (CspB) was overexpressed using the bacteriophage T7 RNA polymerase/promoter system and purified to apparent homogeneity from recombinant Escherichia coli cells. CspB was crystallized in two different forms using vapor diffusion methods. The first crystal form obtained with ammonium sulfate as precipitant belongs to the trigonal crystal system, space group P3(1)21 (P3(2)21) with unit cell dimensions a = b = 59.1 A and c = 46.4 A. The second crystal form is tetragonal, space group P4(1)2(1)2 (P4(3)2(1)2) with unit cell dimensions a = b = 56.9 A and c = 53.0 A. These crystals grow with polyethylene glycol 4000 as precipitant. PMID- 1409561 TI - A systematic search for protein signature sequences. AB - Signature sequences are contiguous patterns of amino acids 10-50 residues long that are associated with a particular structure or function in proteins. These may be of three types (by our nomenclature): superfamily signatures, remnant homologies, and motifs. We have performed a systematic search through a database of protein sequences to automatically and preferentially find remnant homologies and motifs. This was accomplished in three steps: 1. We generated a nonredundant sequence database. 2. We used BLAST3 (Altschul and Lipman, Proc. Natl. Acad. Sci. U.S.A. 87:5509-5513, 1990) to generate local pairwise and triplet sequence alignments for every protein in the database vs. every other. 3. We selected "interesting" alignments and grouped them into clusters. We find that most of the clusters contain segments from proteins which share a common structure or function. Many of them correspond to signatures previously noted in the literature. We discuss three previously recognized motifs in detail (FAD/NAD binding, ATP/GTP-binding, and cytochrome b5-like domains) to demonstrate how the alignments generated by our procedure are consistent with previous work and make structural and functional sense. We also discuss two signatures (for N acetyltransferases and glycerol-phosphate binding) which to our knowledge have not been previously recognized. PMID- 1409562 TI - Modeling of substrate and inhibitor binding to phospholipase A2. AB - Molecular graphics and molecular mechanics techniques have been used to study the mode of ligand binding and mechanism of action of the enzyme phospholipase A2. A substrate-enzyme complex was constructed based on the crystal structure of the apoenzyme. The complex was minimized to relieve initial strain, and the structural and energetic features of the resultant complex analyzed in detail, at the molecular and residue level. The minimized complex was then used as a basis for examining the action of the enzyme on modified substrates, binding of inhibitors to the enzyme, and possible reaction intermediate complexes. The model is compatible with the suggested mechanism of hydrolysis and with experimental data about stereoselectivity, efficiency of hydrolysis of modified substrates, and inhibitor potency. In conclusion, the model can be used as a tool in evaluating new ligands as possible substrates and in the rational design of inhibitors, for the therapeutic treatment of diseases such as rheumatoid arthritis, atherosclerosis, and asthma. PMID- 1409563 TI - A structural model for human dihydrolipoamide dehydrogenase. AB - The hypothesis that dihydrolipoamide dehydrogenases (E3s) have tertiary structures very similar to that of human glutathione reductase (GR) was tested in detail by three separate criteria: (1) by analyzing each putative secondary structural element for conservation of appropriate polar/nonpolar regions, (2) by detailed comparison of putative active site residues in E3s with their authentic counterparts in human GR, and (3) by comparison of residues at the putative dimeric interface of the E3s with the authentic residues in GR. All three criteria are satisfied in a convincing way for the 7 E3s that were considered, supporting the conclusion that the structural scaffolding and the overall tertiary structure (which determines the location of functional sites and residues) are remarkably similar for the E3s and for GR. These analyses together with the crystal structures of human erythrocyte GR formed the basis for construction of a molecular model for human E3. The cofactor FAD and the substrates NAD and lipoic acid were also included in the model. Unexpectedly, the surface residues in the cleft that holds the lipoamide were found to be highly charged and predominantly acidic, allowing us to predict that the region around the lipoamide in the subunit should be basic in nature. The molecular model can be tested by site-directed mutagenesis of residues predicted to be in the dihydrolipoamide acetyltransferase subunit binding cleft. PMID- 1409564 TI - Calmodulin binding to alpha 1-purothionin: solution binding and modeling of the complex. AB - CD and fluorescence spectroscopic measurements show that calmodulin (CaM) binds to purothionins (alpha 1-purothionin: alpha 1-PT; beta-purothionin: beta-PT) in 1:1 stoichiometry with an affinity similar to that exhibited with the tightest binding CaM-binding peptides. Using the available crystal structures of CaM and alpha 1-PT, a model has been built for the interaction of CaM and alpha 1-PT and subjected to potential energy minimization. In the model, there is a bend in the central helix of CaM similar to that suggested by Persechini and Kretsinger (J. Card. Pharm. 12:501-512, 1988). alpha 1-PT fits snugly into the cavity formed by the bent CaM molecule with each of its two helices making apolar interactions with each of the two hydrophobic clefts situated at the terminal domains of CaM. The complex is further stabilized by numerous polar and electrostatic interactions on the rims of the clefts. Our model is compared with two other similar models previously reported for the CaM complexes with other helical peptides and generalizations about the mode of CaM binding to target proteins are made, which have wide relevance to the function of CaM. By analogy, a similar model is predicted for a CaM-beta-PT complex. PMID- 1409565 TI - Fast structure alignment for protein databank searching. AB - A fast method is described for searching and analyzing the protein structure databank. It uses secondary structure followed by residue matching to compare protein structures and is developed from a previous structural alignment method based on dynamic programming. Linear representations of secondary structures are derived and their features compared to identify equivalent elements in two proteins. The secondary structure alignment then constrains the residue alignment, which compares only residues within aligned secondary structures and with similar buried areas and torsional angles. The initial secondary structure alignment improves accuracy and provides a means of filtering out unrelated proteins before the slower residue alignment stage. It is possible to search or sort the protein structure databank very quickly using just secondary structure comparisons. A search through 720 structures with a probe protein of 10 secondary structures required 1.7 CPU hours on a Sun 4/280. Alternatively, combined secondary structure and residue alignments, with a cutoff on the secondary structure score to remove pairs of unrelated proteins from further analysis, took 10.1 CPU hours. The method was applied in searches on different classes of proteins and to cluster a subset of the databank into structurally related groups. Relationships were consistent with known families of protein structure. PMID- 1409566 TI - Functional roles of amino acid residues involved in forming the alpha-helix-turn alpha-helix operator DNA binding motif of Tet repressor from Tn10. AB - The Tn10 derived Tet repressor contains an amino acid segment with high homology to the alpha-helix-turn-alpha-helix motif (HTH) of other DNA binding proteins. The five most conserved amino acids in HTH are probably involved in structural formation of the motif. Their functional role was probed by saturation mutagenesis yielding 95 single amino acid replacement mutants of Tet repressor. Their binding efficiencies to tet operator were quantitatively determined in vivo. All functional mutants contain amino acid substitutions consistent with their proposed role in a HTH. In particular, only the two smallest amino acids (serine, glycine) can substitute a conserved alanine in the proposed first alpha helix without loss of activity. The last position of the first alpha-helix, the second position in the turn, and the fourth position in the second alpha-helix require mostly hydrophobic residues. The proposed C-terminus of the first alpha helix is supported by a more active asparagine compared to glutamine replacement mutant of the wt leucine residue. The turn is located close to the protein surface as indicated by functional lysine and arginine replacements for valine. A glycine residue at the first position in the turn can be replaced by any amino acid yielding mutants with at least residual tet operator affinity. A structural model of the HTH of Tet repressor is presented. PMID- 1409567 TI - Crystal structure of the reduced form of p-hydroxybenzoate hydroxylase refined at 2.3 A resolution. AB - The crystal structure of the reduced form of the enzyme p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens, complexed with its substrate p hydroxybenzoate, has been obtained by protein X-ray crystallography. Crystals of the reduced form were prepared by soaking crystals of the oxidized enzyme substrate complex in deaerated mother liquor containing 300-400 mM NADPH. A rapid bleaching of the crystals indicated the reduction of the enzyme-bound FAD by NADPH. This was confirmed by single crystal spectroscopy. X-ray data to 2.3 A were collected on oscillation films using a rotating anode generator as an X-ray source. After data processing and reduction, restrained least squares refinement using the 1.9 A structure of the oxidized enzyme-substrate complex as a starting model, yielded a crystallographic R-factor of 14.8% for 11,394 reflections. The final model of the reduced complex contains 3,098 protein atoms, the FAD molecule, the substrate p-hydroxybenzoate and 322 solvent molecules. The structures of the oxidized and reduced forms of the enzyme-substrate complex were found to be very similar. The root-mean-square discrepancy for all atoms between both structures was 0.38 A. The flavin ring is almost completely planar in the final model, although it was allowed to bend or twist during refinement. The observed angle between the benzene and the pyrimidine ring is 2 degrees. This value should be compared with observed values of 10 degrees for the oxidized enzyme-substrate complex and 19 degrees for the enzyme-product complex. The position of the substrate is virtually unaltered with respect to its position in the oxidized enzyme. No trace of a bound NADP+ or NADPH molecule was found. PMID- 1409568 TI - Structural principles for the propeller assembly of beta-sheets: the preference for seven-fold symmetry. AB - Twisted beta-sheets, packed face to face, may be arranged in circular formation like blades of a propeller or turbine. This beta-propeller fold has been found in three proteins: that in neuraminidase consists of six beta-sheets while those in methylamine dehydrogenase and galactose oxidase are composed of seven beta sheets. A model for multisheet packing in the beta-propeller fold is proposed. This model gives both geometrical parameters of the beta-propellers composed of different numbers of sheets and patterns of residue packing at their sheet-to sheet interfaces. All the known beta-propeller structures have been analyzed, and the observed geometries and residue packing are found to be in good agreement with those predicted by models. It is shown that unusual seven-fold symmetry is preferable to six- or eight-fold symmetry for propeller-like multi-sheet assembly. According to the model, a six-beta-sheet propeller has to have predominantly small residues in the beta-strands closed to its six-fold axis, but no strong sequence constraints are necessary for a seven-fold beta-propeller. PMID- 1409569 TI - Fast and simple Monte Carlo algorithm for side chain optimization in proteins: application to model building by homology. AB - An unknown protein structure can be predicted with fair accuracy once an evolutionary connection at the sequence level has been made to a protein of known 3-D structure. In model building by homology, one typically starts with a backbone framework, rebuilds new loop regions, and replaces nonconserved side chains. Here, we use an extremely efficient Monte Carlo algorithm in rotamer space with simulated annealing and simple potential energy functions to optimize the packing of side chains on given backbone models. Optimized models are generated within minutes on a workstation, with reasonable accuracy (average of 81% side chain chi 1 dihedral angles correct in the cores of proteins determined at better than 2.5 A resolution). As expected, the quality of the models decreases with decreasing accuracy of backbone coordinates. If the back-bone was taken from a homologous rather than the same protein, about 70% side chain chi 1 angles were modeled correctly in the core in a case of strong homology and about 60% in a case of medium homology. The algorithm can be used in automated, fast, and reproducible model building by homology. PMID- 1409570 TI - Effects of changing the interaction between subdomains on the thermostability of Bacillus neutral proteases. AB - Variants of the thermolabile neutral protease (Npr) of B. subtilis (Npr-sub) and the thermostable neutral protease of B. stearothermophilus (Npr-ste) were produced by means of site-directed mutagenesis and the effects of the mutations on thermostability were determined. Mutations were designed to alter the interaction between the middle and C-terminal subdomain of these enzymes. In all Nprs a cluster of hydrophobic contacts centered around residue 315 contributes to this interaction. In thermostable Nprs (like Npr-ste) a 10 residue beta-hairpin, covering the domain interface, makes an additional contribution. The hydrophobic residue at position 315 was replaced by smaller amino acids. In addition, the beta-hairpin was deleted from Npr-ste and inserted into Npr-sub. The changes in thermostability observed after these mutations confirmed the importance of the hydrophobic cluster and of the beta-hairpin for the structural integrity of Nprs. Combined mutants showed that the effects of individual mutations affecting the interaction between the subdomains were not additive. The effects on thermostability decreased as the strength of the subdomain interaction increased. The results show that once the subdomain interface is sufficiently stabilized, additional stabilizing mutations at the same interface do not further increase thermostability. The results are interpreted on the basis of a model for the thermal inactivation of neutral proteases, in which it is assumed that inactivation results from the occurrence of local unfolding processes that render these enzymes susceptible to autolysis. PMID- 1409572 TI - Fuzzy cluster analysis of molecular dynamics trajectories. AB - We propose fuzzy clustering as a method to analyze molecular dynamics (MD) trajectories, especially of proteins and polypeptides. A fuzzy cluster analysis locates classes of similar three-dimensional conformations explored during a molecular dynamics simulation. The method can be readily applied to results from both equilibrium and nonequilibrium simulations, with clustering on either global or local structural parameters. The potential of this technique is illustrated by results from fuzzy cluster analyses of trajectories from MD simulations of various fragments of human parathyroid hormone (PTH). For large molecules, it is more efficient to analyze the clustering of root-mean-square distances between conformations comprising the trajectory. We found that the results of the clustering analysis were unambiguous, in terms of the optimal number of clusters of conformations, for the majority of the trajectories examined. The conformation closest to the cluster center can be chosen as being representative of the class of structures making up the cluster, and can be further analyzed, for example, in terms of its secondary structure. The CPU time used by the cluster analysis was negligible compared to the MD simulation time. PMID- 1409571 TI - Hydrogen exchange in native and denatured states of hen egg-white lysozyme. AB - The hydrogen exchange kinetics of 68 individual amide protons in the native state of hen lysozyme have been measured at pH 7.5 and 30 degrees C by 2D NMR methods. These constitute the most protected subset of amides, with exchange half lives some 10(5)-10(7) times longer than anticipated from studies of small model peptides. The observed distribution of rates under these conditions can be rationalized to a large extent in terms of the hydrogen bonding of individual amides and their burial from bulk solvent. Exchange rates have also been measured in a reversibly denatured state of lysozyme; this was made possible under very mild conditions, pH 2.0 35 degrees C, by lowering the stability of the native state through selective cleavage of the Cys-6-Cys-127 disulfide cross-link (CM6 127 lysozyme). In this state the exchange rates for the majority of amides approach, within a factor of 5, the values anticipated from small model peptides. For a few amides, however, there is evidence for significant retardation (up to nearly 20-fold) relative to the predicted rates. The pattern of protection observed under these conditions does not reflect the behavior of the protein under strongly native conditions, suggesting that regions of native-like structure do not persist significantly in the denatured state of CM6-127 lysozyme. The pattern of exchange rates from the native protein at high temperature, pH 3.8 69 degrees C, resembles that of the acid-denatured state, suggesting that under these conditions the exchange kinetics are dominated by transient global unfolding. The rates of folding and unfolding under these conditions were determined independently by magnetization transfer NMR methods, enabling the intrinsic exchange rates from the denatured state to be deduced on the basis of this model, under conditions where the predominant equilibrium species is the native state. Again, in the case of most amides these rates showed only limited deviation from those predicted by a simple random coil model. This reinforces the view that these denatured states of lysozyme have little persistent residual order and contrasts with the behavior found for compact partially folded states of proteins, including an intermediate detected transiently during the refolding of hen lysozyme. PMID- 1409573 TI - Selection of a representative set of structures from Brookhaven Protein Data Bank. AB - Reliable structural and statistical analyses of three dimensional protein structures should be based on unbiased data. The Protein Data Bank is highly redundant, containing several entries for identical or very similar sequences. A technique was developed for clustering the known structures based on their sequences and contents of alpha- and beta-structures. First, sequences were aligned pairwise. A representative sample of sequences was then obtained by grouping similar sequences together, and selecting a typical representative from each group. The similarity significance threshold needed in the clustering method was found by analyzing similarities of random sequences. Because three dimensional structures for proteins of same structural class are generally more conserved than their sequences, the proteins were clustered also according to their contents of secondary structural elements. The results of these clusterings indicate conservation of alpha- and beta-structures even when sequence similarity is relatively low. An unbiased sample of 103 high resolution structures, representing a wide variety of proteins, was chosen based on the suggestions made by the clustering algorithm. The proteins were divided into structural classes according to their contents and ratios of secondary structural elements. Previous classifications have suffered from subjective view of secondary structures, whereas here the classification was based on backbone geometry. The concise view lead to reclassification of some structures. The representative set of structures facilitates unbiased analyses of relationships between protein sequence, function, and structure as well as of structural characteristics. PMID- 1409574 TI - A model of the platelet factor 4 complex with heparin. AB - A model of heparin bound to bovine platelet factor 4 (BPF4) was completed using a graphically designed heparin molecule and the crystallographic coordinates of the native bovine platelet factor 4 tetramer. The oligosaccharides had a chain length of at least eight disaccharide units with the major repeating disaccharide unit consisting of (1----4)-O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1----4)-(2 deoxy-2-sulfamino-2-D-glucopyranosyl 6-sulfate). Each disaccharide unit carried a -4.0 charge. The structure of BPF4 was solved to 2.6 A resolution with R = 0.237. Each monomer of BPF4 contains an alpha-helix lying across 3 strands of antiparallel beta-sheet. Each helix has four lysines, which have been implicated in heparin binding. These lysine residues are predominantly on one side of the helix and are solvent accessible. Electrostatic calculations performed on the BPF4 tetramer show a ring of strong, positive charge which runs perpendicularly across the helices. Included in this ring of density is His-38, which has been shown by NMR to have a large pKa shift when heparin binds to BPF4. Our model of heparin bound to PF4 has the anionic polysaccharide perpendicular to the alpha helices, wrapped about the tetramer along the ring of positive charge, and salt linked to all four lysines on the helix of each monomer. PMID- 1409575 TI - Three-dimensional structure of the quinoprotein methylamine dehydrogenase from Paracoccus denitrificans determined by molecular replacement at 2.8 A resolution. AB - The three-dimensional structure of the quinoprotein methylamine dehydrogenase from Paracoccus dentrificans (PD-MADH) has been determined at 2.8 A resolution by the molecular replacement method combined with map averaging procedures, using data collected from an area detector. The structure of methylamine dehydrogenase from Thio-bacillus versutus, which contains an "X-ray" sequence, was used as the starting search model. MADH consists of 2 heavy (H) and 2 light (L) subunits related by a molecular 2-fold axis. The H subunit is folded into seven four stranded beta segments, forming a disk-shaped structure, arranged with pseudo-7 fold symmetry. A 31-residue elongated tail exists at the N-terminus of the H subunit in MADH from T. versutus but is partially digested in this crystal form of MADH from P. denitrificans, leaving the H subunit about 18 residues shorter. Each L subunit contains 127 residues arranged into 10 beta-strands connected by turns. The active site of the enzyme is located in the L subunit and is accessible via a hydrophobic channel between the H and L subunits. The redox cofactor of MADH, tryptophan tryptophylquinone is highly unusual. It is formed from two covalently linked tryptophan side chains at positions 57 and 107 of the L subunit, one of which contains an orthoquinone. PMID- 1409576 TI - Effect of polyethylene glycol-400 at low concentrations on long-term growth of muscle phosphoglucomutase crystals from concentrated salt solutions. AB - Although rabbit muscle phosphoglucomutase occasionally deposits tetragonal crystals from solutions of ammonium sulfate at about 47% of saturation, low concentrations of polyethylene glycol-400 (PEG), 1 to 4.5% w/v, must be included to sustain crystal growth. A comparison of long-term growth rates for macroscopic crystals in the presence and absence of added PEG suggests that at high salt concentration this cosolute exerts its primary effect on disordered protein aggregates, either in the external medium or at the surface of the crystal, and thereby allows the growth of much larger crystals. Since the observed effects may arise from a PEG-induced increase in the "solubility" of the aggregate that exceeds the induced increase in solubility of the crystalline phase under these conditions, the physical basis for a cosolute-induced increase in solubility in the presence of a precipitant is considered. The applicability of such a rationale to the present system is supported by an assessment of the relative effects of polyethylene glycol and beta-octylglucoside on amorphous, salt-induced precipitates of phosphoglucomutase. PEG also produces what appears to be a differential effect on nucleation efficiency and crystal growth rate. Thus, seed crystals cannot be enlarged at a significant rate at high salt concentration without producing showers of extraneous nucleation centers when the concentration of added PEG is 3% or less. But PEG concentrations of 4.5% essentially eliminate the showering problem, ostensibly by increasing the supersaturation required for nucleation to a greater extent than that required for crystal growth. The same type of effect is observed during de novo growth. Again a solubility-based mechanism is posed. Hysteretic effects related to properties of amorphous aggregates of the protein also are described. PMID- 1409577 TI - Multiple protein sequence alignment from tertiary structure comparison: assignment of global and residue confidence levels. AB - An algorithm is presented for the accurate and rapid generation of multiple protein sequence alignments from tertiary structure comparisons. A preliminary multiple sequence alignment is performed using sequence information, which then determines an initial superposition of the structures. A structure comparison algorithm is applied to all pairs of proteins in the superimposed set and a similarity tree calculated. Multiple sequence alignments are then generated by following the tree from the branches to the root. At each branchpoint of the tree, a structure-based sequence alignment and coordinate transformations are output, with the multiple alignment of all structures output at the root. The algorithm encoded in STAMP (STructural Alignment of Multiple Proteins) is shown to give alignments in good agreement with published structural accounts within the dehydrogenase fold domains, globins, and serine proteinases. In order to reduce the need for visual verification, two similarity indices are introduced to determine the quality of each generated structural alignment. Sc quantifies the global structural similarity between pairs or groups of proteins, whereas Pij' provides a normalized measure of the confidence in the alignment of each residue. STAMP alignments have the quality of each alignment characterized by Sc and Pij' values and thus provide a reproducible resource for studies of residue conservation within structural motifs. PMID- 1409578 TI - Molecular cloning and characterization of additional factors that bind to the interferon-alpha/beta response element B of the murine (2'-5')oligoadenylate synthetase ME-12 gene. AB - The function of interferon (IFN) response elements (IREs) may be classified into two classes according to the location of the IRE in the polymerase II transcription promoter: located upstream of the core promoter, or located within the core promoter. Thus, the IRE-binding factors (IREBFs) can serve as sequence specific transcription factors that activate IFN-inducible gene transcription and they can participate in preinitiation complex formation. In the murine and human (2'-5')oligoadenylate synthetase genes the IRE is located within the core promoter region. For this reason, it is important to isolate cDNAs encoding protein factors that can bind to this IRE and determine their functional roles in the regulation of expression of the IFN-inducible (2'-5')oligoadenylate synthetase gene. We have isolated three groups of cDNAs that encode IREBFs. Here we report on clone 38 cDNA, which contains an open reading frame encoding a protein of 277 amino acids that is designated IREBF-2. The C terminus of IREBF-2 is extremely proline-rich and contains a high percentage of short-armed amino acids. IREBF-2 shares marked similarity with some gene products of the herpes group of viruses. These gene products are potent transcription activators. IREBF 2 is constitutively expressed in BALB/c 3T3 cells. PMID- 1409579 TI - Shc proteins are phosphorylated and regulated by the v-Src and v-Fps protein tyrosine kinases. AB - The mammalian shc gene encodes two overlapping proteins of 46 and 52 kDa, each with a C-terminal Src homology 2 (SH2) domain and an N-terminal glycine/proline rich sequence, that induce malignant transformation when overexpressed in mouse fibroblasts. p46shc, p52shc, and an additional 66-kDa shc gene product become highly tyrosine phosphorylated in Rat-2 cells transformed by the v-src or v-fps oncogene. Experiments using temperature-sensitive v-src and v-fps mutants indicate that Shc tyrosine phosphorylation is rapidly induced upon activation of the v-Src or v-Fps tyrosine kinases. These results suggest that Shc proteins may be directly phosphorylated by the v-Src and v-Fps oncoproteins in vivo. In cells transformed by v-src or v-fps, or in normal cells stimulated with epidermal growth factor, Shc proteins complex with a poorly phosphorylated 23-kDa polypeptide (p23). Activated tyrosine kinases therefore regulate the association of Shc proteins with p23 and may thereby control the stimulation of an Shc mediated signal transduction pathway. The efficient phosphorylation of Shc proteins and the apparent induction of their p23-binding activity in v-src- and v fps-transformed cells are consistent with the proposition that the SH2-containing Shc polypeptides are biologically relevant substrates of the oncogenic v-Src and v-Fps tyrosine kinases. PMID- 1409580 TI - Early regional specification for a molecular neuronal phenotype in the rat neocortex. AB - The timing of neocortical regional specification was examined using a monoclonal antibody, designated PC3.1, that binds a 29-kDa polypeptide and recognizes a neuronal subpopulation located in the lateral but not dorsomedial neocortex in the rat. When lateral cortical tissue fragments at embryonic days 12 and 16 were maintained in an organotypic culture system, a substantial number of neurons became PC3.1-immunopositive. In marked contrast, considerably fewer, if any, PC3.1-positive neurons were observed in cultures of dorsal cortical tissue. The selective appearance of PC3.1-immunopositive neurons was also observed in dissociated cultures derived from the lateral, but not dorsal, cortical primordium at embryonic day 13 and later. In light of previous reports showing that the interactions between developing neocortical neurons and cortical afferents begin at embryonic day 14 or later, our findings imply that some regional specification occurs well before these interactions and suggest the importance of elements intrinsic to the neocortex in establishing neocortical regional specificity. Furthermore, [3H]thymidine birth-dating experiments revealed that the majority of presumptive PC3.1-immunopositive neurons underwent their final mitosis around embryonic day 15, suggesting that the regional specification events for these neurons occur before their neurogenesis. PMID- 1409581 TI - An inhibitory carboxyl-terminal domain in Ets-1 and Ets-2 mediates differential binding of ETS family factors to promoter sequences of the mb-1 gene. AB - The mb-1 gene is expressed only during the early stages of B-lymphocyte differentiation. Here we show that the mb-1 proximal promoter region contains a functionally important binding site for members of the ETS family of DNA-binding proteins. We found that both the E26 virus-encoded v-ets and the myeloid/B-cell specific factor PU.1 bind efficiently to this site in vitro. By contrast, Ets-1, the lymphocyte-specific cellular homologue of v-ets, and the related, more ubiquitously expressed Ets-2 protein interacted weakly with this binding site. DNA binding by both Ets-1 and Ets-2, however, could be increased 20- to 50-fold by deleting as few as 16 carboxyl-terminal amino acids. The inhibitory carboxyl terminal amino acid sequence is highly conserved between Ets-1 and Ets-2 but is not present in either v-ets or PU.1. Replacement of the carboxyl-terminal amino acids of v-ets with those of Ets-1 decreased DNA binding by v-ets drastically. Cotranslation of Ets-1 transcripts encoding proteins of different lengths suggested that Ets-1 binds DNA as a monomer. Therefore, the carboxyl-terminal inhibitory domain appears to interfere directly with DNA binding and not with homodimerization. Finally, the functional relevance of ETS factor binding to the mb-1 promoter site was evidenced by the stimulation of transcription through this site by a v-myb-v-ets fusion protein. Together, these data suggest that one or more ETS family factors are involved in the regulation of mb-1 gene expression. PMID- 1409582 TI - High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains. AB - Src homology 2 domains bind to tyrosine-phosphorylated growth factor receptors and are found in proteins that serve as substrates for tyrosine kinases, such as phospholipase C-gamma 1 and ras GTPase-activating protein. We have previously described the cloning of phosphatidylinositol 3'-kinase-associated p85 from expression libraries with the tyrosine-phosphorylated epidermal growth factor receptor as a probe. We have now modified this technique by using T7 polymerase based expression libraries, which significantly improves sensitivity of the method. In one screening of such a library, we identified five different murine Src homology 2 domain-containing proteins, which we call GRBs (growth factor receptor-bound proteins). Two of these proteins represented the tyrosine kinase fyn and the mouse homologue of phospholipase C-gamma 1, whereas two genes encoded proteins similar to v-crk and NCK. We also isolated the gene for GRB-7, which encodes a protein of 535 amino acids. In addition to a Src homology 2 domain, GRB 7 also has a region of similarity to the noncatalytic domain of ras GTPase activating protein and is highly expressed in liver and kidney. Use of this expression/cloning system should increase our ability to identify downstream modulators of growth factor action. PMID- 1409584 TI - Centromere DNA mutations induce a mitotic delay in Saccharomyces cerevisiae. AB - Cytological observations of animal cell mitoses have shown that the onset of anaphase is delayed when chromosome attachment to the spindle is spontaneously retarded or experimentally interrupted. This report demonstrates that a centromere DNA (CEN) mutation carried on a single chromosome can induce a cell cycle delay observed as retarded mitosis in the yeast Saccharomyces cerevisiae. A 31-base-pair deletion within centromere DNA element II (CDEII delta 31) that causes chromosome missegregation in only 1% of cell division elicited a dramatic mitotic delay phenotype. Other CEN DNA mutations, including mutations in centromere DNA elements I and III, similarly delayed mitosis. Single division pedigree analysis of strains containing the CDEII delta 31 CEN mutation indicated that most (and possibly all) cells experienced delay in each cell cycle and that the delay was not due to increased chromosome copy number. Furthermore, a synchronous population of cells containing the CDEII delta 31 mutation underwent DNA synthesis on schedule with wild-type kinetics, but subsequently exhibited late chromosomal separation and concomitant late cell separation. We speculate that this delay in cell cycle progression before the onset of anaphase provides a mechanism for the stabilization of chromosomes with defective kinetochore structure. Further, we suggest that the delay may be mediated by surveillance at a cell cycle checkpoint that monitors the completion of chromosomal attachment to the spindle. PMID- 1409583 TI - Bacterial ADP-ribosyltransferase with a substrate specificity of the rho protein disassembles the Golgi apparatus in Vero cells and mimics the action of brefeldin A. AB - Epidermal-cell differentiation inhibitor (EDIN) is an exoenzyme produced by Staphylococcus aureus that catalyzes the ADP-ribosylation of rho proteins, members of the small GTP-binding protein family. In this study we demonstrate that EDIN induces a rapid morphological change in the Golgi structure of monkey kidney Vero cells that is similar to the changes elicited by brefeldin A (BFA). Treatment of Vero cells with EDIN resulted in a rapid disappearance of N-7-(4 nitrobenzo-2-oxa-1,3-diazole)-6-aminocaproylsphingosine, a 110-kDa protein (beta COP, coat protein), and mannosidase II from the Golgi structure. Lower doses of EDIN and BFA had a synergistic effect on the redistribution of the Golgi markers. The similarities in the effects of EDIN and BFA in Vero cells also include the EDIN- or BFA-mediated protection of Vero cells from ricin cytotoxicity and prevention of the effects of EDIN or BFA on the distribution of Golgi markers by the pretreatment of Vero cells with guanosine 5'-[gamma-thio]triphosphate or forskolin. Incubation of a Vero-cell homogenate with [32P]NAD+ and EDIN in vitro resulted in the appearance of a labeled band with an apparent molecular mass of 22 kDa. The morphological change of the Golgi structure induced by EDIN was inhibited by nicotinamide, an inhibitor of EDIN-catalyzed ADP-ribosylation. Thus these data suggest that a rho protein is involved in the membrane trafficking between the Golgi and the endoplasmic reticulum of Vero cells and that this rho protein may be a target shared by EDIN and BFA. PMID- 1409585 TI - Identification of a second insulin-like growth factor in a fish species. AB - An internal portion of insulin-like growth factor (IGF) amplified from the total cDNA of rainbow trout (Oncorhynchus mykiss) liver by a PCR was used to screen a rainbow trout liver cDNA library, and recombinant clones encoding two distinct IGFs were isolated. On the basis of a 98.7% nucleotide and 98.3% predicted amino acid identity to coho salmon IGF-I, one cDNA sequence was identified as rainbow trout preproinsulin-like growth factor I (rtIGF-I). The second cDNA sequence shared 46.1% and 43.3% identity with rtIGF-I at the nucleotide and predicted amino acid levels, respectively, and was identified as rainbow trout preproinsulin-like growth factor II (rtIGF-II). Predicted amino acid sequence comparisons of rtIGFs with those of human IGFs indicate that rtIGF-I is more similar to human IGF-I than to human IGF-II, and that rtIGF-II is more similar to human IGF-II than to human IGF-I. Southern blot analysis of rainbow trout genomic DNA probed with rtIGF-I and -II cDNA suggests that these two forms of IGF originate from separate genes. The presence of a teleost IGF-II suggests that the divergence of IGFs occurred early in vertebrate evolution. PMID- 1409586 TI - Analysis of the association of peptides of optimal length to class I molecules on the surface of cells. AB - The association of major histocompatibility complex (MHC) class I molecules on the surface of cells with synthetic antigenic peptides of eight or nine amino acid residues was examined. Peptides were synthesized that correspond to the antigenic sequences from ovalbumin and influenza nucleoprotein believed to be naturally processed and presented by cells with Kb and Db MHC class I molecules, respectively. Consistent with the results of others, these peptides were 10(3) 10(5) times more active in stimulating specific T cells as compared to peptides of longer sequences. When cells are incubated with these peptides at less than 0.01-0.1 microM, the association of the peptides with class I molecules is dependent on (i) the reassociation of free beta 2-microglobulin from the extracellular fluids, (ii) a process that requires cells to be metabolically active, or (iii) stabilization of class I heterodimers by chemical crosslinking. In contrast, when cells are incubated with these peptides at greater than 0.1-1.0 microM, the peptides associate with class I molecules in the absence of exogenous beta 2-microglobulin, energy, or chemical crosslinking. Antigen competition experiments suggest that the class I molecules that bind peptides offered at high concentration become only transiently receptive to binding peptide. The concentration of peptides required for presentation to T cells under these conditions corresponds to those that stabilize Kb molecules on the surface of RMA S mutant cells in the absence of exogenous beta 2-microglobulin. These results support the concept that the receptivity of class I molecules on cells is determined by the dissociation of beta 2-microglobulin from MHC class I that lacks bound peptides. PMID- 1409587 TI - Monomers and dimers of the RepA protein in plasmid pSC101 replication: domains in RepA. AB - The replication of plasmid pSC101 requires the plasmid-encoded protein RepA. This protein has a double role: it binds to three directly repeated sequences in the pSC101 origin and promotes replication of the plasmid; it binds to two inversely repeated sequences in its promoter region and regulates its own transcription. A series of RepA protein derivatives carrying deletions of the C-terminal region were assayed for specific binding. We found that the last third of the protein is not needed for binding to the various specific sites. Truncated proteins that still bind can also form heterodimers with a wild-type protein. Analysis of band retardation assays conducted with wild-type and truncated proteins indicates that RepA binds to directly repeated sequences as a monomer and to inversely repeated sequences as a dimer. PMID- 1409588 TI - Cloning and characterization of an androgen-induced growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells. AB - An androgen-dependent mouse mammary carcinoma cell line (SC-3) requires androgen for growth stimulation. We have shown previously that androgen acts on SC-3 cells to induce secretion of a fibroblast growth factor (FGF)-like growth factor, which in turn stimulates growth of the cells in an autocrine manner. In this study, the androgen-induced growth factor (AIGF) was purified from a conditioned medium of SC-3 cells stimulated with testosterone. cDNA cloning of AIGF by use of its partial amino acid sequence data revealed that AIGF is a distinctive FGF-like growth factor. An AIGF cDNA (pSC17) encodes a 215-amino acid protein with a putative signal peptide, which shares 30-40% homology with known members of the FGF family. The AIGF mRNA was markedly induced by 10 nM testosterone in Northern blot analysis. Expression of AIGF cDNA in mammalian cells clearly showed remarkable stimulatory effects of AIGF on growth of SC-3 cells in the absence of androgen. Thus, it is clear that the androgen-induced growth of SC-3 cells is mediated in an autocrine manner by AIGF, which is secreted by the tumor cells themselves in response to hormonal stimuli. PMID- 1409589 TI - Defective guanyl nucleotide-binding protein beta gamma subunits in a forskolin resistant mutant of the Y1 adrenocortical cell line. AB - Forskolin-resistant mutants derived from Y1 adrenocortical cells display decreased responsiveness both to receptor and postreceptor stimulators of adenylyl cyclase and decreased amounts of the alpha subunits of the GTP-binding proteins (G proteins) that mediate stimulation (Gs) and inhibition (Gi) of adenylyl cyclase--namely, Gs alpha and Gi alpha-2. This phenotype is suggestive of a mutation that affects the processing or plasma membrane incorporation of G protein alpha subunits. Since the membrane attachment of heterotrimeric G proteins has been ascribed in part to the beta gamma subunits, we examined the quantity and functional activity of beta gamma subunits in wild-type Y1 and forskolin-resistant Forsk-10r-9 and Forsk-10r-3 cells. We now show that two assays previously used to examine the activity of purified beta gamma subunits- namely, to support either rhodopsin-catalyzed guanyl nucleotide exchange on Gt alpha or pertussis toxin-catalyzed ADP-ribosylation of Gt alpha--can be used with detergent extracts of cells. In both assays the beta gamma activity in Forsk-10r 9 and Forsk-10r-3 extracts was decreased by 53-76% compared with wild-type Y1 extracts. When normalized for immunoreactive beta subunit, the beta gamma activity in the Forsk-10r-9 samples was decreased by 55-57% compared with the wild-type Y1 samples. These results suggest that a mutation of one of the G protein beta or gamma subunits may result in the multiple defects of adenylyl cyclase activity and apparent loss of G protein alpha subunits seen in the forskolin-resistant mutant cells. The frequency with which these spontaneous mutations arise in the Y1 cell line suggests that they may contribute more generally to genetic abnormalities in signal transduction. PMID- 1409590 TI - Emr, an Escherichia coli locus for multidrug resistance. AB - An Escherichia coli chromosomal DNA fragment cloned on a multicopy plasmid conferred resistance to carbonylcyanide m-chlorophenylhydrazone, nalidixic acid, and a number of other toxic compounds. The sequence of the cloned emr locus located at minute 57.5 of the chromosome revealed two open reading frames, emrA and emrB. emrB encodes a highly hydrophobic 56.2-kDa peptide, with 14 potential alpha-helices to span the inner membrane. The peptide is homologous to QacA, a multidrug-resistant pump from Staphylococcus aureus, and belongs to a gene family that includes tetracycline-resistant pumps of Gram-positive bacteria and the galactose/H+ symporter of E. coli. emrA encodes a putative 42.7-kDa peptide containing a single hydrophobic domain and a large C-terminal hydrophilic domain. An active pho-fusion to the C domain suggested that EmrA is a membrane protein. Disruption of emrB significantly increased sensitivity of cells to uncouplers. The cellular content of uncoupler increased in the order: overexpressed emrB cells greater than wild type greater than emrB-. PMID- 1409591 TI - Antifreeze protein modulates cell survival during cryopreservation: mediation through influence on ice crystal growth. AB - Antifreeze proteins (AFPs) are extremely efficient at inhibiting ice recrystallization in frozen solutions. Knight and Duman [Knight, C. A. & Duman, J. G. (1986) Cryobiology 23, 256-263] have proposed that this may be an important function of the proteins in freeze-tolerant organisms. We have tested this proposal in vitro by characterizing the influence of AFP on the recovery of cryopreserved cells, which often can survive cooling and yet subsequently be damaged by ice crystal growth during warming. Relatively low concentrations (e.g., 5-150 micrograms/ml) of winter flounder (Pseudopleuronectes americanus) AFP enhance survival of red blood cells cryopreserved in hydroxyethyl starch solutions. This effect is most apparent in samples warmed at suboptimal rates, i.e., where ice recrystallization would be exaggerated. Cryomicroscopy demonstrates that AFP inhibits ice recrystallization in the extracellular regions during the latter stages of the warming cycle. AFP concentrations that enhance survival of red cells confer partial inhibition of recrystallization. Relatively high concentrations of AFP (e.g., 1.54 mg/ml) are much more effective at inhibiting extracellular recrystallization. However, extensive growth of ice around the cell, and concomitant cell damage, is noted. The mechanism for this AFP-induced ice growth is unknown. We propose that there is a delicate balance between AFP-induced enhancement of cell preservation and AFP-induced enhancement of cell preservation and AFP-induced enhancement of cell damage and that this balance hinges on the degrees of inhibition of ice recrystallization and of preferential growth of ice around the cells. We conclude that, under appropriate conditions, one of the proposed functions of AFPs in nature can be emulated, and perhaps have application, in cryopreservation of materials of biomedical interest. PMID- 1409592 TI - Divergent evolution of pyrimidine biosynthesis between anaerobic and aerobic yeasts. AB - A cDNA encoding the dihydroorotate dehydrogenase (DHOdehase; EC 1.3.3.1) of the yeast Schizosaccharomyces pombe was isolated by functional complementation in Saccharomyces cerevisiae. A divergent subcellular compartmentation of the DHOdehase of each yeast was shown. The DHOdehase from Sch. pombe was localized in the mitochondria whereas its homolog from S. cerevisiae was found to be cytosolic. The heterologous expression of the Sch. pombe enzyme in S. cerevisiae allowed us to demonstrate that the Sch. pombe DHOdehase activity requires the integrity of the mitochondrial electron transport chain. Indeed, the presence of a mutation inactivating cytochrome b abolished the complementation of a S. cerevisiae ura1 mutant by the corresponding Sch. pombe gene. By contrast, in vitro studies have revealed that the DHOdehase of S. cerevisiae uses fumarate as terminal electron acceptor. These results are discussed in relation to the anaerobic growth competence of the two yeasts and to the fermentative processes they use. PMID- 1409593 TI - Structure and expression of major histocompatibility complex-binding protein 2, a 275-kDa zinc finger protein that binds to an enhancer of major histocompatibility complex class I genes. AB - We have isolated a cDNA encoding a transcription factor that binds to the enhancer of major histocompatibility complex (MHC) class I genes. MHC-binding protein 2 (MBP-2) is a 275-kDa protein, containing two sets of widely separated zinc fingers and a stretch of highly acidic amino acids, a putative transactivation domain. The two zinc finger regions, when expressed individually as bacterial fusion proteins, bind with highest affinity to the MHC class I gene enhancer. Several proteins found in mammalian nuclear extracts bind the MHC class I enhancer in an electrophoresis mobility shift assay. Only one of these, a ubiquitously expressed factor, forming a slow-migrating retarded complex, can be supershifted by a MBP-2 antiserum. The same antiserum also precipitates a protein of greater than 250 kDa from COS cells transfected with a MBP-2 expression vector. Our data indicate that MBP-2 is a transcription factor involved in the regulation of MHC class I gene expression. PMID- 1409594 TI - Proposed acquisition of an animal protein domain by bacteria. AB - A systematic screen of a protein sequence data base confirms that the fibronectin type III (Fn3) domain is widely distributed among animal proteins and occurs also in several bacterial carbohydrate-splitting enzymes. The motif has yet to be identified in proteins from plants or fungi. All indications are that the bacterial sequences are much too similar to the animal type to be the result of conventional vertical descent. Rather, it is likely that the bacterial units were initially acquired from an animal source and are being spread further by horizontal transfers between distantly related bacteria. PMID- 1409595 TI - A strategy for making synthetic peptide vaccines. AB - We have determined the H-2 class II allele-specific amino acid motif of the agretope (the site of contact between the peptide antigen and the major histocompatibility complex) for a synthetic peptide composed of residues 43-58 of pigeon cytochrome c (p43-58). Residues 46 and 54 functioned as the agretope, and residues 50 and 52 functioned as the epitope (the site for contact between the peptide antigen and the T-cell antigen receptor). In general, agretopes and epitopes function independently. Thus, substitution of amino acids in the epitope does not significantly affect binding of the peptide antigen to a class II molecule. On the basis of these findings, synthetic peptide vaccines against influenza Aichi (H3N2) virus were prepared by introducing seven residues of the influenza virus hemagglutinin into the frame component residues 43-46 and 54-58 of p43-58 analogues including the agretopes for Ak or Ab previously determined on the p43-58 segment. These peptide vaccines induced both helper T-cell responses and production of antibodies that were specific for influenza Aichi hemagglutinin but not for the major histocompatibility complex binding frame in mice bearing Ak or Ab. The antibodies produced neutralize the infectivity of influenza Aichi in vitro. The present findings should provide a basis for preparing potent peptide vaccines that function without producing side effects. PMID- 1409596 TI - Cellular and peptide requirements for in vitro clonal deletion of immature thymocytes. AB - Thymocytes from DO10 T-cell-receptor transgenic mice undergo apoptosis, or programmed cell death, when chicken ovalbumin-(323-339) peptide is administered in vivo. Using DO10 mice thymocytes, we have now developed a simple in vitro model system that recapitulates the in vivo clonal-deletion process. When transgenic thymocytes were cocultured with fibroblasts, B cells, or thymic nurse cell lines (all bearing I-Ad) in the presence of chicken ovalbumin-(323-339), deletion of the transgenic TCR+CD4+CD8+ thymocytes was seen within 8-20 hr. Thymocytes designed to bear I-Ad on their surface could mediate the deletion themselves. Thus, thymocyte clonal deletion entirely depends on the stage at which the thymocytes are vulnerable to the onset of apoptosis, rather than on the nature of the peptide antigen-presenting cells. Furthermore, thymic nurse cell line TNC-R3.1 could cause deletion, strongly suggesting that some thymic epithelial/stromal components are potentially capable of participating in negative selection. In all cases examined, little deletion could be induced at a peptide concentration less than 10 nM, thus defining the minimum amount of peptide antigen required for negative selection. The peptide-dependent in vitro negative-selection system will allow further dissection of the molecular and cellular processes involved in clonal deletion due to apoptosis in the thymus. PMID- 1409597 TI - Ionizing radiation stimulates unidentified tyrosine-specific protein kinases in human B-lymphocyte precursors, triggering apoptosis and clonogenic cell death. AB - Very little is known regarding the effects of ionizing radiation on cytoplasmic signal transduction pathways. Here, we show that ionizing radiation induces enhanced tyrosine phosphorylation of multiple substrates in human B-lymphocyte precursors. This response to ionizing radiation was also observed in cells pretreated with vanadate, a potent protein-tyrosine-phosphatase (PTPase) inhibitor, and phosphotyrosyl [Val5]angiotensin II phosphatase assays showed no decreased PTPase activity in irradiated cells. Thus, enhanced tyrosine phosphorylation in irradiated B-lymphocyte precursors is not triggered by inhibition of total cellular PTPase activity. Immune-complex kinase assays using anti-phosphotyrosine antibodies demonstrated enhanced protein-tyrosine kinase (PTK) activity in the immunoprecipitates from irradiated cells, and the PTK inhibitors genistein and herbimycin effectively prevented radiation-induced tyrosine phosphorylation. Immune-complex kinase assays on irradiated and unirradiated B-lymphocyte precursors using antibodies prepared against unique amino acid sequences of p59fyn, p56/p53lyn, p55blk, and p56lck demonstrated that these Src-family tyrosine kinases were not the primary PTKs responsible for enhanced tyrosine kinase activity in the anti-phosphotyrosine antibody immunoprecipitates or for enhanced tyrosine phosphorylation of multiple substrates. Thus, our findings favor the hypothesis that ionizing radiation induces enhanced tyrosine phosphorylation in B-lymphocyte precursors by stimulation of as yet unidentified PTKs. Tyrosine phosphorylation appears to be an important proximal step in radiation-induced apoptosis and clonogenic cell death because inhibition of PTK prevents DNA fragmentation and loss of clonogenicity of irradiated B-lymphocyte precursors. Since PTKs play myriad roles in the regulation of cell function and proliferation, the activation of a PTK cascade, as detailed in this report, may explain some of the pleiotropic effects of ionizing radiation on cellular functions of B-lymphocytes and their precursors. PMID- 1409598 TI - Another perspective on the visual motion aftereffect. AB - Prolonged adaptation to motion in a given direction produces distinctly different visual motion aftereffects (MAEs) when viewing static vs. dynamic test displays. The dynamic MAE can be exactly simulated by real motion, whereas the static MAE cannot. In addition, the magnitude of the dynamic MAE depends on the bandwidth of motion directions experienced during adaptation, whereas the static MAE does not. Evidently a stationary pattern does not directly activate the neural mechanisms affected during motion adaptation, whereas a dynamic visual display does. These results imply that the traditional explanation of the MAE needs modification. PMID- 1409599 TI - Protein tertiary structure recognition using optimized Hamiltonians with local interactions. AB - Protein folding codes embodying local interactions including surface and secondary structure propensities and residue-residue contacts are optimized for a set of training proteins by using spin-glass theory. A screening method based on these codes correctly matches the structure of a set of test proteins with proteins of similar topology with 100% accuracy, even with limited sequence similarity between the test proteins and the structural homologs and the absence of any structurally similar proteins in the training set. PMID- 1409600 TI - Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes. AB - The successful treatment of cancer by boron neutron-capture therapy (BNCT) requires the selective concentration of boron-10 within malignant tumors. The potential of liposomes to deliver boron-rich compounds to tumors has been assessed by the examination of the biodistribution of boron delivered by liposomes in tumor-bearing mice. Small unilamellar vesicles with mean diameters of 70 nm or less, composed of a pure synthetic phospholipid (distearoyl phosphatidylcholine) and cholesterol, have been found to stably encapsulate high concentrations of water-soluble ionic boron compounds. The hydrolytically stable borane anions B10H10(2-), B12H11SH2-, B20H17OH4-, B20H19(3-), and the normal form and photoisomer of B20H18(2-) were encapsulated in liposomes as their soluble sodium salts. The tissue concentration of boron in tumor-bearing mice was measured at several time points over 48 h after i.v. injection of emulsions of liposomes containing the borane anions. Although the boron compounds used do not exhibit an affinity for tumors and are normally rapidly cleared from the body, liposomes were observed to selectively deliver the borane anions to tumors. The highest tumor concentrations achieved reached the therapeutic range (greater than 15 micrograms of boron per g of tumor) while maintaining high tumor-boron/blood boron ratios (greater than 3). The most favorable results were obtained with the two isomers of B20H18(2-). These boron compounds have the capability to react with intracellular components after they have been deposited within tumor cells by the liposome, thereby preventing the borane ion from being released into blood. PMID- 1409601 TI - Downregulation of interleukin 8 gene expression in human fibroblasts: unique mechanism of transcriptional inhibition by interferon. AB - The chemotactic cytokine interleukin 8 (IL-8) is produced upon stimulation by various agents in many cell types, including connective-tissue fibroblasts. Tumor necrosis factor (TNF) and IL-1 are potent inducers of IL-8 expression. Earlier we showed that TNF-induced stimulation of IL-8 mRNA accumulation in human FS-4 fibroblasts was inhibited by interferon beta (IFN-beta) or IFN-gamma. Here we show that this inhibition is not specific for TNF, since IFN-beta also reduced IL 8 mRNA accumulation induced by IL-1 or the double-stranded RNA poly (I-C). Treatment with IFN-beta also decreased TNF-induced IL-8 protein accumulation. Interestingly, the inhibitory effect was much less pronounced when IFN-beta was added greater than or equal to 1 hr before TNF. The inhibitory action of IFN-beta on IL-8 mRNA accumulation was undiminished in the presence of inhibitors of protein synthesis. Nuclear run-on assays demonstrated that IFN-beta caused a marked inhibition of TNF-induced IL-8 gene transcription; the transcriptional activation of several other TNF-induced genes was not inhibited by IFN-beta. The results suggest that the specific inhibition of the transcriptional activation of IL-8 by IFN is due either to a transient inactivation of a factor required for IL 8 transcription or to the activation of a selective inhibitory factor. PMID- 1409602 TI - In the presence of dexamethasone, gamma interferon induces rat oligodendrocytes to express major histocompatibility complex class II molecules. AB - Cells that express major histocompatibility complex (MHC) class II molecules can interact directly with CD4 T lymphocytes and either activate immune reactions or become the targets of T-cell-mediated cytotoxic attack. Using rat optic nerve cultures combined with immunocytochemistry and in situ hybridization, we have shown that oligodendrocytes, the major myelin-forming cells of the central nervous system and the main casualty of the immune attacks associated with multiple sclerosis and experimental allergic encephalomyelitis, can be readily induced to express MHC class II mRNA and surface antigens in vitro by exposure to gamma interferon, provided the glucocorticoid dexamethasone is included in the culture medium. Oligodendrocytes exposed to gamma interferon without dexamethasone fail to express MHC class II molecules, which may account for the failure of previous attempts to induce expression in these cells. In the experiments reported here MHC class II expression can be demonstrated both on galactocerebroside-positive cells and on mature oligodendrocytes that express proteolipid protein. These findings expand possibilities for understanding immune related oligodendrocyte killing and demyelination in human and experimental demyelinating diseases. PMID- 1409604 TI - Gene transfer of a reserpine-sensitive mechanism of resistance to N-methyl-4 phenylpyridinium. AB - The toxin N-methyl-1,2,3,6-tetrahydropyridine produces a model of neural degeneration very similar to idiopathic Parkinson disease. To understand the cellular mechanisms that modulate susceptibility to its active metabolite N methyl-4-phenylpyridinium (MPP+), we have transfected a cDNA expression library from the relatively MPP(+)-resistant rat pheochromocytoma PC12 cells into MPP(+) sensitive Chinese hamster ovary (CHO) fibroblasts. Selection of the stable transformants in high concentrations of MPP+ has yielded a clone extremely resistant to the toxin. Reserpine reverses the resistance to MPP+, suggesting that a transport activity protects against this form of toxicity, perhaps by sequestering the toxin within an intracellular compartment. In support of this hypothesis, dopamine loaded into the CHO transformant shows a localized distribution that is distinct from the pattern observed in wild-type cells and is also reversed by reserpine. PMID- 1409603 TI - Glucocorticoid-induced formation of tight junctions in mouse mammary epithelial cells in vitro. AB - Phenotypically stable cultures of untransformed mouse mammary epithelial cells (denoted 31EG4) were established and utilized to investigate the lactogenic hormone (glucocorticoids, insulin, and prolactin) regulation of tight junction formation. When 31EG4 cells were grown on permeable supports for 4 days in medium containing the synthetic glucocorticoid dexamethasone and insulin, confluent cell monolayers obtained a transepithelial electrical resistance (TER) of 1000-3000 omega.cm2. In contrast, over the same time period, confluent monolayers treated with insulin or insulin and prolactin maintained a low TER (35-150 omega.cm2). Consistent with the formation of tight junctions, apical to basolateral paracellular permeability was decreased from 12% to 1% for [14C]mannitol and 3.3% to 0.3% for [3H]inulin when cells were cultured in dexamethasone. This effect of dexamethasone on TER required extracellular calcium, de novo protein synthesis, dose-dependently correlated with glucocorticoid receptor occupancy, and was not due to an increase in cell density. As shown by direct and indirect immunofluorescence microscopy, dexamethasone treatment did not modulate the production or location of filamentous actin, the tight junction protein ZO-1, or the cell adhesion protein E-cadherin. Our results suggest that glucocorticoids play a fundamental role in the function and maintenance of cell-cell contact in the mammary epithelia by inducing the formation of tight junctions. PMID- 1409605 TI - Cell-specific expression of a Clara cell secretory protein-human growth hormone gene in the bronchiolar epithelium of transgenic mice. AB - Clara cell secretory protein (CCSP) is an abundant 10-kDa protein synthesized and secreted by nonciliated epithelial cells lining the respiratory and terminal bronchioles of the lung. CCSP gene expression is an informative developmental marker within the bronchiolar epithelium recapitulating cellular differentiation in the distal respiratory epithelium during late fetal and early postnatal life. To define the mechanisms that establish and maintain gene expression within this epithelium, CCSP-human growth hormone chimeric gene constructs were created and used to generate transgenic mice. RNA blot analysis of organs from F1 transgenic offspring and normal littermates revealed that cis-acting elements within 2.25 kilobases of the 5' flanking region of the CCSP gene were sufficient to direct lung-specific expression of human growth hormone. In situ hybridization and immunohistochemistry of individual bronchioles revealed that human growth hormone expression in the respiratory epithelium of these mice was confined to Clara cells, consistent with observations of the endogenous CCSP gene. Unexpectedly, founder animals and F1 transgenic offspring exhibited an unusual phenotype of growth retardation and delayed hair appearance, suggesting a unique effect of human growth hormone on normal intrauterine development. CCSP-human growth hormone transgenic mice provide a model to dissect the developmental mechanisms regulating gene expression during pulmonary epithelial cell growth and differentiation. Definition of the cis-acting elements determining such cell specific expression will be of value in strategies for the somatic gene therapy of human pulmonary disease. PMID- 1409606 TI - Precursor structure, expression, and tissue distribution of human guanylin. AB - Heat-stable enterotoxins (STa) are small, cysteine-rich peptides secreted by Escherichia coli that are able to induce diarrhea through the stimulation of an intestine-specific receptor-guanylyl cyclase known as STaR. A 15-amino acid peptide, guanylin, was recently purified from rat jejunum and proposed to be a potential endogenous activator of this receptor. We describe here the cloning and characterization of human and mouse cDNAs encoding precursor proteins of 115 and 116 amino acids, respectively, having guanylin present at their C termini. Expression of the human cDNA in mammalian cells leads to the secretion of proguanylin, an inactive 94-amino acid protein. Guanylin generated by either trypsin or acid treatment of proguanylin was purified and found to bind to, and activate, STaR. Northern blot and in situ hybridization show high-level expression of guanylin mRNA restricted to the intestine, with localization to Paneth cells at the base of the small intestinal crypts. These results demonstrate that guanylin is an endogenous activator of STaR. PMID- 1409607 TI - Protein stitchery: design of a protein for selective binding to a specific DNA sequence. AB - We present a general strategy for designing proteins to recognize DNA sequences and illustrate this with an example based on the "Y-shaped scissors grip" model for leucine-zipper gene-regulatory proteins. The designed protein is formed from two copies, in tandem, of the basic (DNA binding) region of v-Jun. These copies are coupled through a tripeptide to yield a "dimer" expected to recognize the sequence TCATCGATGA (the v-Jun-v-Jun homodimer recognizes ATGACTCAT). We synthesized the protein and oligonucleotides containing the proposed binding sites and used gel-retardation assays and DNase I footprinting to establish that the dimer binds specifically to the DNA sequence TCATCGATGA but does not bind to the wild-type DNA sequences, nor to oligonucleotides in which the recognition half-site is modified by single-base changes. These results also provide strong support for the Y-shaped scissors grip model for binding of leucine-zipper proteins. PMID- 1409608 TI - Molecular cloning of a candidate chicken prion protein. AB - Fractions enriched for acetylcholine receptor-inducing activity from chicken brain were found to contain a protein that was approximately 30% homologous with mammalian prion proteins [Harris, D. A., Falls, D. L., Johnson, F. A. & Fischbach, G. D. (1991) Proc. Natl. Acad. Sci. USA 88, 7664-7668]. To extend these observations, we recovered genomic clones encoding a putative chicken prion protein (PrP). Like mammalian PrP molecules, the candidate chicken PrP is encoded by a single-copy gene and the entire open reading frame is found within a single exon. All of the structural features of mammalian PrP were found in the chicken protein. When the N-terminal repeats of PrP were not considered, the chicken and mammalian proteins were approximately 55% homologous, allowing for conservative substitutions. Screening of a chicken genomic DNA library failed to identify a more closely related chicken PrP homologue. These findings argue that the protein which purifies with acetylcholine receptor-inducing activity is chicken PrP. PMID- 1409609 TI - Mapping genes in the mouse using single-strand conformation polymorphism analysis of recombinant inbred strains and interspecific crosses. AB - We have utilized a PCR-based analysis of single-strand conformation polymorphisms to identify polymorphisms that can be used for mapping cloned DNA sequences in the mouse. We have found that single-strand conformation polymorphism analysis of sequences that are potentially less subject to conservation (i.e., intron and 3' untranslated regions) is a relatively efficient means of detecting polymorphisms between inbred strains. Fifty percent of the tested primer pairs were polymorphic between inbred strains and 90% were polymorphic between mouse species, which is a frequency comparable to that found for microsatellite repeat sequences. We have found that this technique can be readily used to determine the strain distribution pattern in a recombinant inbred series and is a simple and rapid means to obtain a map position for cloned sequences. When this strategy was tested on a number of previously mapped cloned genes, the strain distribution patterns obtained were consistent with that to be expected on the basis of the known map position. We also tested the utility of this approach for characterizing genes that have not been previously mapped. Dvl, the mouse homolog of the putative Drosophila dishevelled gene, and Adfp, encoding an adipocyte differentiation-related protein, were found to map to chromosome 4. These results were confirmed using single-strand conformation polymorphism analysis of an interspecific backcross. PMID- 1409610 TI - Fc epsilon RI-mediated tyrosine phosphorylation and activation of the 72-kDa protein-tyrosine kinase, PTK72, in RBL-2H3 rat tumor mast cells. AB - In RBL-2H3 rat tumor mast cells, cross-linking the high-affinity IgE receptor Fc epsilon RI causes tyrosine phosphorylation of multiple proteins. These phosphoproteins include phospholipase C gamma 1, the beta and gamma subunits of the Fc epsilon RI, the Src family protein-tyrosine kinase Lyn, and a 72-kDa protein that coimmunoprecipitates from lysates of antigen-stimulated cells with antibody to the receptor beta subunit. We now present evidence that the 72-kDa Fc epsilon RI-associated protein is the protein-tyrosine kinase PTK72 that forms part of the antigen receptor complex in B lymphocytes. The identification is based on immunoreactivity with anti-PTK72 antiserum, chromatographic profiles on the affinity resin heparin/agarose, and one-dimensional phosphopeptide mapping studies. Enzymatic activity of the kinase is increased in anti-PTK72 immune complexes prepared from lysates of antigen-activated RBL-2H3 cells. The 72-kDa protein-tyrosine kinase is the principal substrate for in vitro tyrosine phosphorylation in anti-phosphotyrosine immunoprecipitates of RBL-2H3 cells. The discovery that RBL-2H3 mast cells share a receptor-activated protein-tyrosine kinase, PTK72, with B lymphocytes provides additional support for the existence of common signaling pathways initiated by multichain immune recognition receptors. PMID- 1409611 TI - Protein oxidation associated with aging is reduced by dietary restriction of protein or calories. AB - The accumulation of unrepaired oxidative damage products may be a major factor in cellular aging. Both oxidative lesions in DNA and oxidatively damaged proteins have been shown to accumulate during aging. The accumulation of oxidized proteins in Fischer 344 rats was compared for animals consuming protein-restricted and calorically restricted diets--both of which have been shown to extend lifespan. Rats were fed diets restricted in either protein (5% or 10% of the diet as compared with the normal 20% casein), or calories (25% or 40% less than normal), or total diet (40% less than normal). In addition, some of the rats fed a diet providing 5% or 20% protein were irradiated twice weekly (125 rads per exposure; 1 rad = 0.01 Gy). The level of oxidative damage to proteins (protein carbonyls) was determined in rats sacrificed at various times. The oxidative damage to proteins increased with aging and with radiation. Either protein or calorie restriction markedly inhibited the accumulation of oxidatively damaged proteins. Protein restriction reduced the accumulation of oxidatively damaged proteins during the oxidative stress of chronic irradiation. PMID- 1409612 TI - Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1. AB - Interleukin 1 (IL-1) is a cytokine released during immune activation that mediates the host's response to infection and inflammation. Peripheral and central injections of IL-1 induce fever and sickness behavior, including decreased food motivation and reduced interest in social activities. To determine the receptor mechanisms responsible for these effects, rats were injected with IL 1 receptor antagonist (IL-1ra), an endogenous cytokine that acts as a pure antagonist of IL-1 receptors. IL-1ra blocked the increased body temperature and oxygen consumption induced by injection of recombinant human IL-1 only when both cytokines were administered i.p. In contrast, i.p. or intracerebroventricular administration of IL-1ra blocked the depressive effect of IL-1 beta on food motivated behavior and social exploration when this cytokine was administered by the same route as the antagonist. In addition, intracerebroventricular IL-1ra blocked the reduction in social exploration produced by i.p. IL-1 beta but had only partial antagonist effects on the decrease in food-motivated behavior induced by i.p. IL-1 beta. In each case, the dose of IL-1ra was 100- to 1000-fold in excess of the biologically active dose of IL-1. These results suggest that the receptor mechanisms that mediate the behavioral and pyrogenic effects of IL-1 are heterogeneous. PMID- 1409613 TI - Accurate and rapid detection of heterozygous carriers of a deletion by combined polymerase chain reaction and high-performance liquid chromatography. AB - We have developed a technique to detect accurately heterozygous carriers of a deletion. Specific target sequences were amplified by the polymerase chain reaction (PCR), and the products subsequently were analyzed by high-performance liquid chromatography. Examples from four loci demonstrated that 24-27 cycles of amplification for a single-copy DNA, based on 50 ng of genomic DNA, results in excellent quantitation that readily permits the detection of heterozygous carriers of a deletion. We have demonstrated that triplex PCR (three targets in a single PCR) entails no loss of precision. We also have demonstrated that this method can accurately differentiate the heterozygous carriers of a deletion from normal individuals in four family studies, three for Duchenne muscular dystrophy patients and one for a hemophilia B patient. PMID- 1409614 TI - Expression of myosin-class II major histocompatibility complexes in the normal myocardium occurs before induction of autoimmune myocarditis. AB - Determining how an autoimmune response is initiated is essential to understanding the mechanisms of autoimmunity. Self-reactive T cells, self-protein, and a failure of tolerance to that self-protein are all involved in the pathogenesis of autoimmune disease; yet it is not clear how self-reactive T cells find the target self-protein to initiate an autoimmune response. Although a variety of self proteins have been shown to be presented on both class I and class II major histocompatibility complex (MHC) molecules, the relationship of these self proteins to autoimmune disease has not been established. To explore this further, we generated a T-cell hybridoma that recognizes mouse cardiac myosin, the self protein that induces murine autoimmune myocarditis. Using this hybridoma as a probe to detect myosin-class II MHC complexes, we isolated a class II MHC+/CD45+ residential antigen-presenting cell (APC) population directly from the hearts of normal mice and looked for evidence of endogenous processing of cardiac myosin by these APC. In this report we show that myosin-class II MHC complexes are found on residential APC in the normal mouse heart. Induction of autoimmune myocarditis increased the expression of myosin-class II MHC in the heart and enhanced their APC functions. This result is a direct demonstration that epitopes of a self antigen involved in initiating an autoimmune disease are endogenously processed and presented within the target organ. PMID- 1409615 TI - Agroinfection as an alternative to insects for infecting plants with beet western yellows luteovirus. AB - Beet western yellows luteovirus, like other luteoviruses, cannot be transmitted to host plants by mechanical inoculation but requires an aphid vector, a feature that has heretofore presented a serious obstacle to the study of such viruses. In this paper we describe use of agroinfection to infect hosts with beet western yellows virus without recourse to aphids. Agroinfection is a procedure for introducing a plant virus into a host via Agrobacterium tumefaciens harboring a Ti plasmid, which can efficiently transfer a portion of the plasmid (T-DNA) to plant cells near a wound. The viral genome must be inserted into the T-DNA in such a way that it can escape and begin autonomous replication, a requirement that has, so far, limited agroinfection to pathogens with a circular genome. We have cloned cDNA corresponding to the complete beet western yellows virus RNA genome between the cauliflower mosaic virus 35S promoter and the nopaline synthase transcription termination signal. In one construct, a self-cleaving (ribozyme) sequence was included so as to produce a transcript in planta with a 3' extremity almost identical to natural viral RNA. When inoculated mechanically to host plants, the naked plasmid DNA was not infectious but, when introduced into T-DNA and agroinfected to plants, both the construct with and without the ribozyme produced an infection. This approach should be applicable to virtually any plant virus with a linear plus-strand RNA genome. PMID- 1409616 TI - Expression cloning of a human cDNA encoding folylpoly(gamma-glutamate) synthetase and determination of its primary structure. AB - A human cDNA for folypoly(gamma-glutamate) synthetase [FPGS; tetrahydrofolate:L glutamate gamma-ligase (ADP forming), EC 6.3.2.17] has been cloned by functional complementation of an Escherichia coli folC mutant. The cDNA encodes a 545 residue protein of M(r) 60,128. The deduced sequence has regions that are highly homologous to peptide sequences obtained from purified pig liver FPGS and shows limited homology to the E. coli and Lactobacillus casei FPGSs. Expression of the cDNA in E. coli results in elevated expression of an enzyme with characteristics of mammalian FPGS. Expression of the cDNA in AUXB1, a mammalian cell lacking FPGS activity, overcomes the cell's requirement for thymidine and purines but does not overcome the cell's glycine auxotrophy, consistent with expression of the protein in the cytosol but not the mitochondria. PMID- 1409617 TI - Coat protein gene duplication in a filamentous RNA virus of plants. AB - Computer-assisted analysis revealed a striking sequence similarity between the putative 24-kDa protein (p24) encoded by open reading frame (ORF) 5 of beet yellows closterovirus and the coat protein of this virus encoded by the adjacent ORF6. Both of these proteins are closely related to the homologous proteins of another closterovirus, citrus tristeza virus. It is hypothesized that the genes for coat protein and its diverged tandem copy have evolved by duplication. Phylogenetic analysis using various methods for tree generation suggested that the duplication was already present in the genome of the common ancestor of the two closteroviruses. The genes for p24 and coat protein of beet yellows closterovirus were cloned, transcribed, and translated in vitro yielding products of the expected size. It was shown that p24 is translated starting from the first of the two alternative AUG codons located near the 5' terminus of ORF5. The presence of a single protein species in beet yellows closterovirus virions and the near identity of the amino acid composition of this protein with the composition of the ORF6 but not the ORF5 product indicated that p24 is not a major virion component. Most of the amino acids that are conserved in the coat proteins of filamentous viruses of plants are retained also in p24. These observations suggest that p24 may share some structural and functional features with the coat protein but probably fulfills a distinct function in virus reproduction. PMID- 1409618 TI - Translocation of apolipoprotein B across the endoplasmic reticulum is blocked in a nonhepatic cell line. AB - To explore the process of lipoprotein assembly, plasmids encoding truncated forms of apolipoprotein B (apoB) were transfected into Chinese hamster ovary (CHO) fibroblasts. (One, encoding apoB53, the N-terminal 53% of apoB100, can direct the assembly and secretion of lipoproteins when expressed in hepatoma cells, while the other, encoding the shorter apoB15, does not direct lipoprotein assembly.) Expression of apoB15 in CHO cells resulted in the accumulation of apoB15 protein in both medium and cells. In contrast, apoB was not detectable in medium or within CHO cells transfected with the plasmid encoding apoB53, despite the expression of apoB53 mRNA. ApoB53 did accumulate within transfected cells incubated with the thiol protease inhibitor N-acetylleucylleucylnorleucinal (ALLN), suggesting that it is synthesized but completely degraded in the absence of the inhibitor. ApoB53 was not secreted despite its presence within ALLN treated cells. Essentially all the apoB53 that accumulated in microsomes from ALLN-treated cells was associated with the membrane and was susceptible to degradation by exogenous trypsin, indicating exposure on the cytoplasmic face of the membrane. Thus, translocation of apoB53 across the endoplasmic reticulum membrane is blocked. However, the apoB53 bound to concanavalin A, suggesting that it is glycosylated and therefore partly exposed to the lumen as well. ApoB requires a unique process, not expressed in CHO fibroblasts, for its complete translocation and entrance into the secretory pathway. This process might account for the inability of abetalipoproteinemic patients to secrete apoB. PMID- 1409619 TI - Uncoupling gene activity from chromatin structure: promoter mutations can inactivate transcription of the yeast HSP82 gene without eliminating nucleosome free regions. AB - DNase I-hypersensitive sites represent "nucleosome-free" regions in chromatin where the underlying DNA sequence is highly accessible to trans-acting proteins. Here we demonstrate that it is possible to uncouple gene activity from hypersensitive site formation. Point or substitution mutations were introduced into the promoter of the yeast chromosomal HSP82 gene, encoding the 83-kDa heat shock protein (HSP), via site-directed integration. Mutating either the TATA box or heat shock element 1 (HSE1) significantly reduced basal and heat-induced transcription while mutating both essentially inactivated expression. Dormant transcription units exhibited arrays of sequence-positioned nucleosomes; nevertheless, the inactivated genes still retained a hypersensitive site within their mutated promoters. In addition, all yeast strains maintained a heat inducible hypersensitive site at -600 base pairs (bp), while several mutant strains converted a constitutive hypersensitive site at -300 bp into a heat inducible one. Thus, mutations in cis-acting elements within a promoter can inactivate transcription without eliminating nucleosome-free regions. PMID- 1409620 TI - In vitro differentiation of embryonic stem cells into lymphocyte precursors able to generate T and B lymphocytes in vivo. AB - Embryonic stem cells can be induced in vitro, by coculture with the stromal line RP.0.10 and a mixture of interleukins 3, 6, and 7, to differentiate into T (Joro75+) and B (B-220+) lymphocyte progenitors and other (Thy-1+, PgP-1+, c kit+, Joro75-, B-220-, F4/80-, Mac-1-) hemopoietic precursors. The progeny of in vitro-induced embryonic stem cells can reconstitute the lymphoid compartments of T- and B-lymphocyte-deficient scid mice and generate mature T and B lymphocytes in sublethally irradiated normal mice. Exogenous cytokines can dramatically alter the developmental fate of embryonic stem cells in culture. The in vitro system described here should facilitate the study of molecular events leading to cell lineage commitment and to the formation of hemopoietic stem cells and their immediate lymphoid progeny. PMID- 1409621 TI - Characterization of Plasmodium falciparum sporozoite surface protein 2. AB - Immunization of mice with Plasmodium yoelii sporozoite surface protein 2 (PySSP2) and circumsporozoite protein protects completely against P. yoelii. The amino acid sequence of PySSP2 suggested that the thrombospondin-related anonymous protein (TRAP) [Robson, K. J. H., Hall, J. R. S., Jennings, M. W., Harris, T. J. R., Marsh, K., Newbold, C. I., Tate, V. E. & Weatherall, D. J. (1988) Nature (London) 335, 79-82] is the Plasmodium falciparum homolog of PySSP2. We report data confirming that TRAP is P. falciparum SSP2 (PfSSP2). Murine antibodies against recombinant PfSSP2 identify a 90-kDa protein in extracts of P. falciparum sporozoites, recognize sporozoites and infected hepatocytes by immunofluorescence, localize PfSSP2 to the sporozoite micronemes by immunoelectron microscopy and to the surface membrane by live immunofluorescence, and inhibit sporozoite invasion and development in hepatocytes in vitro. Human volunteers immunized with irradiated sporozoites and protected against malaria develop antibody and proliferative T-cell responses to PfSSP2, suggesting that, like PySSP2, PfSSP2 is a target of protective immunity, and supporting inclusion of PfSSP2 in a multicomponent malaria vaccine. PMID- 1409622 TI - Anion sensitivity and spectral tuning of cone visual pigments in situ. AB - We tested the effect of anions on the absorbance spectrum of native visual pigments as measured by microspectrophotometry in individual cone outer segments of four species of fish and one species of amphibian. In all species tested, the long-wavelength-absorbing cone pigments were anion sensitive, and their lambda max could be tuned over a range of 55 nm depending on the identity of the anion present. Cl- and Br- were the only anions that produced native pigment spectra by red shifting lambda max from its value under anion-free conditions. Lyotropic anions such as NO3-, SCN-, BF4-, and ClO4- caused substantial and graded blue shifts of lambda max. The apparent Kd of binding sites on the pigment for Cl- and for ClO4- was approximately 2 mM. Taken together with previous findings on three visual pigments from the reptilian, avian, and amphibian classes, our results support the hypothesis that all long-wavelength-absorbing vertebrate visual pigments are spectrally tuned in part through the binding of a chloride ion. We propose that the site of anion tuning is near the protonated Schiff base of the chromophore, whose counterion may be complex and include Cl- as an exchangeable anion. This counterion configuration may resemble the one present in the light driven Cl- pump halorhodopsin. PMID- 1409623 TI - Interactions between natural polyamines and tRNA: an 15N NMR analysis. AB - 15N NMR spectroscopy was used to explore the interactions between natural polyamines and Escherichia coli tRNA. It was found that when tRNA is added to solutions of 15N-labeled spermine or spermidine, there is a considerable decrease in the relative heights of the -NH(2+)--resonances with respect to the signals arising from the -NH3+ groups. The presence of tRNA was also found to reduce the longitudinal relaxation times T1 of the nitrogens, mainly those of the -NH(2+)- groups. The longitudinal relaxation times of the nitrogens were used to characterize the temperature dependence of the binding, and they allowed us to calculate the activation energies that determine the correlation times of amino groups in the presence of tRNA. Both the thermodynamic and the relaxation results indicate that (i) spermine binds more strongly to tRNA than spermidine does and (ii) within each of these molecules the -NH(2+)- groups bind more strongly to tRNA than the more electropositive -NH3+ moieties. This specificity suggests that the interaction between polyamines and tRNA cannot be described exclusively in terms of electrostatic forces and that other interactions (most likely, hydrogen bonding) are very important for establishing the polyamine-tRNA link. Some of the factors that may conspire against the binding of -NH3+ groups to tRNA are briefly discussed. PMID- 1409624 TI - Phagocytosis of liposomes by human platelets. AB - We have shown that platelets are capable of phagocytosing liposomes rather than simply sequestering particles as previously postulated. Incubation of human platelets with small neutral unilamellar liposomes (approximately 74 nm) resulted in uptake of the liposomes and retention of the lipid with rapid release of the aqueous-phase components. The lipid label [3H]-cholesterylhexadecyl ether and water-soluble [3H]inulin were used to study the fate of the liposome components. Uptake of liposomes was proportional to the number of liposomes added and to the incubation time. Approximately 250 liposomes per platelet were taken up within a 5-hr incubation period. Uptake of the liposomes occurred through the open-channel system, as evidenced by thin-section electron microscopy, and was followed by accumulation and degradation in acid- and esterase-containing vesicles, as determined by changes in fluorescence of the pH-sensitive probe, pyranine (1 hydroxypyrene-3,6,8-trisulfonic acid), and hydrolysis of the cholesteryl [14C]oleate membrane marker. Uptake was inhibited by the addition of EDTA, cytochalasin B, or 2,4-dinitrophenol and iodoacetate to the medium. Results from the serotonin release assay, micro-aggregation assay, fluorescein diacetate membrane integrity assay, and electron microscopy indicate that neither the conditions for loading nor phagocytosis of liposomes significantly alter platelet function or morphology. PMID- 1409625 TI - Efficient mass transformation of Tetrahymena thermophila by electroporation of conjugants. AB - Conjugating cells of the ciliate Tetrahymena thermophila were electroporated in the presence of plasmid DNA containing a paromomycin-resistant ribosomal RNA gene (rDNA). Cells were selected with paromomycin following 12-24 hr of growth on nonselective medium. Resistant cells appeared after 2-3 days. Processing vectors containing the micronuclear rDNA and somatic vectors containing the macronuclear gene transformed the cells, with the former yielding frequencies up to 900 transformants per microgram of plasmid DNA. A ribosomal protein gene (rpL29) conferring cycloheximide resistance also transformed conjugating cells. The transformation efficiency of the plasmid containing only the rpL29 gene was increased by insertion of an rDNA replication origin and by cotransformation and preselection with an rDNA vector. These results indicate that electroporation can be used for the production of large numbers of transformed Tetrahymena. PMID- 1409626 TI - Growth arrest induced by wild-type p53 protein blocks cells prior to or near the restriction point in late G1 phase. AB - Conditional expression of wild-type (wt) p53 protein in a glioblastoma tumor cell line has been shown to be growth inhibitory. We have now more precisely localized the position in the cell cycle where growth arrest occurs. We show that growth arrest occurs prior to or near the restriction point in late G1 phase of the cell cycle. The effect of wt p53 protein on the expression of four immediate-early genes (c-FOS, c-JUN, JUN-B, and c-MYC), one delayed-early gene (ornithine decarboxylase), and two late-G1/S-phase genes (B-MYB and DNA polymerase alpha) was also examined. Of this subset of growth response genes, only the expression of B-MYB and DNA polymerase alpha was significantly repressed. The possibility that decreased expression of B-MYB may be an important component of growth arrest mediated by wt p53 protein is discussed. PMID- 1409627 TI - Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression. AB - Recently we reported that human dermal fibroblasts, or conditioned media obtained from such cells, affect the growth of human melanoma cells as a direct function of tumor progression: melanoma cells obtained from early-stage (metastatically incompetent) primary lesions were growth inhibited, whereas cells obtained from more advanced (metastatically competent) primary lesions, or metastases, were growth stimulated. Ion-exchange and gel-filtration chromatography of fibroblast conditioned medium revealed the inhibitor to be a protein of molecular mass between 20 and 30 kDa and distinct from the stimulator. This is the approximate molecular mass of interleukin 6 (IL-6), a ubiquitous multifunctional cytokine known to affect in particular many kinds of hemopoietic and lymphoid cells. Since this cytokine is known to be made by fibroblasts, we attempted to determine if the human fibroblast-derived growth inhibitor (hFDGI) was identical to IL-6. Neutralizing antibodies specific for IL-6 completely eliminated the inhibitory activity of hFDGI. Moreover, exposure to human recombinant IL-6 was found to inhibit the growth of early-stage melanoma cells obtained from radial growth phase (RGP) or early vertical growth phase (VGP) primary lesions in three of four cases. In contrast, melanoma cells from a number of more advanced VGP primary lesions, or from distant metastases, were completely resistant to this IL-6 mediated growth inhibition. Acquisition of an "IL-6-resistant" phenotype by metastatically competent melanoma cell variants may provide such cells with a proliferative advantage within the dermal mesenchyme (a hallmark of melanoma cells that are malignant), helping them eventually to dominate advanced primary lesions and to establish secondary growths elsewhere. PMID- 1409628 TI - Combination of H-box [CCTACC(N)7CT] and G-box (CACGTG) cis elements is necessary for feed-forward stimulation of a chalcone synthase promoter by the phenylpropanoid-pathway intermediate p-coumaric acid. AB - The phenylpropanoid pathway intermediate p-coumaric acid (4-CA) stimulates expression of the bean (Phaseolus vulgaris L.) chalcone synthase (malonyl-CoA:4 coumaroyl-CoA, EC 2.3.1.74) chs15 gene promoter in electroporated protoplasts of alfalfa (Medicago sativa L.). We have analyzed the effects of 5' deletions, mutations, and competition with promoter sequences in trans on the expression of a chs15 promoter-chloramphenicol acetyltransferase gene fusion in elicited alfalfa protoplasts. Two distinct sequence elements, the H-box (consensus CCTACC(N)7CT) and the G-box (CACGTG), are required for stimulation of the chs15 promoter by 4-CA. Furthermore, a 38-base-pair chs15 promoter sequence containing both cis elements conferred responsiveness to 4-CA on the cauliflower mosaic virus 35S minimal promoter. The H-box and G-box in combination establish the complex developmental pattern of chs15 expression and are also involved in stress induction. Hence, potential internal pathway regulation through feed-forward stimulation by 4-CA operates by modulation of the signal pathways for developmental and environmental regulation. PMID- 1409629 TI - Single-stranded nucleic acid helical secondary structure stabilized by ionic bonds: d(A(+)-G)10. AB - We have identified a type of secondary structure for the homopurine oligomer d(A G)10 below pH 6 in 0.01 M Na+ that is characterized by intense CD but only minor hypochromicity. The stability of this helix, designated d(A(+)-G)10, does not depend on oligomer concentration and increases sharply as ionic strength or pH drops, reaching a maximum at 4.0 (melting temperature, 37 degrees C). The pKa for the transition, 5.3 at 25 degrees C and even higher with decreasing temperature and [Na+], is much higher than the intrinsic pKa values for dA or dG residues. While the dA residues are protonated in the helix, further protonation of the dG residues disrupts it. When observed at 280 nm, melting of the helix first results in hypochromicity due to stacking of extrahelical dG residues with neighboring dA residues. The character and temperature dependence of the CD spectra of the constituent dinucleoside monophosphates indicate minimal chirality and base overlap for the A+pG sequences in d(A(+)-G)10 but left-handed twist with some base overlap for the GpA+ sequences. The observed properties are best satisfied by a model for an intramolecular helix with limited base overlap, stabilized by ionic bonds between dA residues protonated at N-1 and downstream negatively charged phosphates brought close due to the backbone helical twist, while Gsyn residues lie external to the helix. This structure could provide additional stabilizing energy for biologically relevant protonated non-B-DNA structures adopted by homopurine.homopyrimidine sequences due to topological stress or specific protein binding. PMID- 1409630 TI - "Enzymogenesis": classical liver alcohol dehydrogenase origin from the glutathione-dependent formaldehyde dehydrogenase line. AB - Analysis of the activity and structure of lower vertebrate alcohol dehydrogenases reveals that relationships between the classical liver and yeast enzymes need not be continuous. Both the ethanol activity of class I-type alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) and the glutathione-dependent formaldehyde activity of the class III-type enzyme [formaldehyde:NAD+ oxidoreductase (glutathione-formylating), EC 1.2.1.1] are present in liver down to at least the stage of bony fishes (cod liver: ethanol activity, 3.4 units/mg of protein in one enzyme; formaldehyde activity, 4.5 units/mg in the major form of another enzyme). Structural analysis of the latter protein reveals it to be a typical class III enzyme, with limited variation from the mammalian form and therefore with stable activity and structure throughout much of the vertebrate lineage. In contrast, the classical alcohol dehydrogenase (the class I enzyme) appears to be the emerging form, first in activity and later also in structure. The class I activity is present already in the piscine line, whereas the overall structural-type enzyme is not observed until amphibians and still more recent vertebrates. Consequently, the class I/III duplicatory origin appears to have arisen from a functional class III form, not a class I form. Therefore, ethanol dehydrogenases from organisms existing before this duplication have origins separate from those leading to the "classical" liver alcohol dehydrogenases. The latter now often occur in isozyme forms from further gene duplications and have a high rate of evolutionary change. The pattern is, however, not simple and we presently find in cod the first evidence for isozymes also within a class III alcohol dehydrogenase. Overall, the results indicate that both of these classes of vertebrate alcohol dehydrogenase are important and suggest a protective metabolic function for the whole enzyme system. PMID- 1409631 TI - Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains. AB - The three-dimensional structure of BirA, the repressor of the Escherichia coli biotin biosynthetic operon, has been determined by x-ray crystallography and refined to a crystallographic residual of 19.0% at 2.3-A resolution. BirA is a sequence-specific DNA-binding protein that also catalyzes the formation of biotinyl-5'-adenylate from biotin and ATP and transfers the biotin moiety to other proteins. The level of biotin biosynthetic enzymes in the cell is controlled by the amount of biotinyl-5'-adenylate, which is the BirA corepressor. The structure provides an example of a transcription factor that is also an enzyme. The structure of BirA is highly asymmetric and consists of three domains. The N-terminal domain is mostly alpha-helical, contains a helix-turn-helix DNA binding motif, and is loosely connected to the remainder of the molecule. The central domain consists of a seven-stranded mixed beta-sheet with alpha-helices covering one face. The other side of the sheet is largely solvent-exposed and contains the active site. The C-terminal domain comprises a six-stranded, antiparallel beta-sheet sandwich. The location of biotin binding is consistent with mutations that affect enzymatic activity. A nearby loop has a sequence that has been associated with phosphate binding in other proteins. It is inferred that ATP binds in this region, adjacent to the biotin. It is proposed that the binding of corepressor to monomeric BirA may promote DNA binding by facilitating the formation of a multimeric BirA-corepressor-DNA complex. The structural details of this complex remain an open question, however. PMID- 1409632 TI - Striking effects of coupling mutations in the acceptor stem on recognition of tRNAs by Escherichia coli Met-tRNA synthetase and Met-tRNA transformylase. AB - We measured kinetic parameters in vitro and directly analyzed aminoacylation and formylation levels in vivo to study recognition of Escherichia coli initiator tRNA mutants by E. coli Met-tRNA synthetase and Met-tRNA transformylase. We show that, in addition to the anticodon sequence, mutations in the "discriminator" base A73 also affect aminoacylation. An A73----U change has a small effect, but a change to G73 or C73 significantly lowers Vmax/Kappm for in vitro aminoacylation and leads to appreciable accumulation of uncharged tRNA in vivo. Significantly, coupling of the G73 mutation with G72, a neighboring-base mutation, results in a tRNA essentially uncharged in vivo. Coupling of C73 and U73 mutations with G72 does not have such an effect. Elements crucial for Met-tRNA transformylase recognition of tRNAs are located at the end of the acceptor stem. These elements include a weak base pair or a mismatch between nucleotides (nt) 1 and 72 and base pairs 2.71 and 3.70. The natures of nt 1 and 72 are less important than the fact that they do not form a strong Watson-Crick base pair. Interestingly, the negative effect of a C.G base pair between nt 1 and 72 is suppressed by mutation of the neighboring nucleotide A73 to either C73 or U73. The presence of C73 or U73 could destabilize the C1.G72 base pair at the end of an RNA helix. Thus, in some tRNAs, the discriminator base could affect stability of the base pair between nt 1 and 72 and thereby the structure of tRNA at the end of the acceptor stem. PMID- 1409633 TI - AKT2, a putative oncogene encoding a member of a subfamily of protein serine/threonine kinases, is amplified in human ovarian carcinomas. AB - We isolated cDNA clones containing the entire coding region of the putative oncogene AKT2. Sequence analysis and in vitro translation demonstrated that AKT2 encodes a 56-kDa protein with homology to serine/threonine kinases; moreover, this protein contains a Src homology 2-like domain. AKT2 was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. AKT2 was mapped to chromosome region 19q13.1-q13.2 by fluorescence in situ hybridization. In the two ovarian carcinoma cell lines exhibiting amplification of AKT2, the amplified sequences were localized within homogeneously staining regions. We conclude that AKT2 belongs to a distinct subfamily of protein-serine/threonine kinases containing Src homology 2-like domains and that alterations of AKT2 may contribute to the pathogenesis of ovarian carcinomas. PMID- 1409634 TI - Differential interaction of ADP-ribosylation factors 1, 3, and 5 with rat brain Golgi membranes. AB - Six mammalian ADP-ribosylation factors (ARFs) identified by cDNA cloning were expressed as recombinant proteins (rARFs) that stimulated cholera toxin ADP ribosyltransferase activity. Microsequencing of soluble ARFs I and II (sARFs I and II), purified from bovine brain, established that they are ARFs 1 and 3, respectively. Rabbit antibodies (IgG) against sARF II reacted similarly with ARFs 1, 2, and 3 (class I) on Western blots. ARFs 1 and 3 were distinguished by their electrophoretic mobilities. Antiserum against rARF 5 cross-reacted partially with rARF 4 but not detectably with rARF 6 and minimally with class I ARFs. Guanosine 5'-O-(3-thiotriphosphate) (GTP[gamma S]) increased recovery of ARF activity and immunoreactivity in organelle fractions separated by density gradient centrifugation, after incubation of rat brain homogenate with ATP and a regenerating system. ARF 1 accumulated in microsomes plus Golgi and Golgi fractions, whereas ARF 5 seemed to localize more specifically in Golgi; the smaller increment in ARF 3 was distributed more evenly among fractions. On incubation of Golgi with a crude ARF fraction, GTP[gamma S], and an ATP regenerating system, association of ARF activity with Golgi increased with increasing ATP concentration paralleled by increases in immunoreactive ARFs 1 and 5 and, to a lesser degree, ARF 3. Golgi incubated with GTP[gamma S] and purified ARF 1 or 3 bound more ARF 1 than ARF 3. Based on immunoreactivity and assay of ARF activity, individual ARFs 1, 3, and 5 appeared to behave independently and selectively in their GTP-dependent association with Golgi in vitro. PMID- 1409635 TI - Regulation of thyroid hormone receptor-mediated transcription by a cytosol protein. AB - Thyroid hormone receptors (TRs) are members of the steroid hormone/retinoic acid receptor superfamily, which regulate homeostasis, development, and differentiation. Their transcriptional activity is modulated by the thyroid hormone 3,3',5-triiodo-L-thyronine (T3). The present study evaluated the effect of the availability of cytoplasmic T3 on the modulation of transcriptional responses of the TRs. In human choriocarcinoma JEG-3 and monkey COS-1 cells, the cytosolic thyroid hormone binding protein is a monomer of the tetrameric pyruvate kinase, subtype M2, which does not bind T3. The in vivo monomer-tetramer interconversion is regulated by glucose via fructose 1,6-bisphosphate. At the physiological T3 concentration, lowering the glucose concentration led to an increase in the cellular concentration of the cytosolic thyroid hormone binding protein. By using a transient transfection system, a concomitant reduction in the transcriptional activity of the human beta 1 thyroid hormone receptor was detected in both cell lines. In the absence of glucose, the transcriptional activity of the human beta 1 thyroid hormone receptor in JEG-3 and COS-1 cells was reduced by 65-75% and 90-95%, respectively. However, glucose had no effect on the basal transcriptional activity. These findings demonstrate an important prenuclear step in the modulation of the gene regulating activity of the TRs. PMID- 1409636 TI - A sarcomeric alpha-actinin truncated at the carboxyl end induces the breakdown of stress fibers in PtK2 cells and the formation of nemaline-like bodies and breakdown of myofibrils in myotubes. AB - In many nonmuscle cells, nonsarcomeric alpha-actinin is distributed in the dense bodies of stress fibers, adhesion plaques, and adherens junctions. In striated muscle, a sarcomeric isoform of alpha-actinin (s-alpha-actinin) is found in the Z bands of myofibrils and subsarcolemmal adhesion plaques. To understand the role(s) of the alpha-actinin isoforms in the assembly and maintenance of such cytoskeletal structures, full-length or truncated s-alpha-actinin cDNAs were expressed in PtK2 cells and in primary skeletal myogenic cells. We found the following. (i) In transfected PtK2 cells the truncated s-alpha-actinin was rapidly incorporated into preexisting dense bodies, adhesion plaques, and adherens junctions. With time these structures collapsed, and the affected cells detached from the substrate. (ii) In myotubes the truncated s-alpha-actinin was incorporated into nascent Z-bands. Many of these progressively hypertrophied, forming nemaline-like bodies. With time the affected myofibrils fragmented, and the myotubes detached from the substrate. (iii) In both cell types the truncated s-alpha-actinin was significantly more disruptive of the cytoskeletal structures than the full-length molecule. (iv) Pools of "over-expressed" full-length or truncated protein did not self-aggregate into homogeneous, amorphous complexes; rather the exogenous proteins selectively colocalized with the same cohort of cytoskeletal proteins with which the endogenous alpha-actinin normally associates. The similarity among the hypertrophied Z-bands in transfected myotubes, the nemaline bodies in patients with nemaline myopathies, and the streaming Z-bands seen in various muscle pathologies raises the possibility that the genetically determined nemaline bodies and the pathologically induced Z-band alterations may reflect primary and/or post-translational modifications of s alpha-actinin. PMID- 1409637 TI - Emergence of the keratinocyte growth factor multigene family during the great ape radiation. AB - The structural gene for human keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, consists of three coding exons and two introns typical of other fibroblast growth factor loci. A portion of the KGF gene, located on chromosome 15, is amplified to approximately 16 copies in the human genome, and these highly related copies (which consist of exon 2, exon 3, the intron between them, and a 3' noncoding segment of the KGF transcript) are dispersed to multiple human chromosomes. The KGF-like sequences are transcriptionally active, differentially regulated in various tissues, and composed of three distinct classes of coding sequences that are 5% divergent from each other and from the authentic KGF sequence. Multiple copies of KGF-like genes were also discovered in the genomic DNAs of chimpanzee and gorilla but were not found in lesser apes (gibbon), Old World monkeys (African green monkey and macaques), mice, or chickens. The pattern of evolutionary occurrence suggests that a primordial KGF gene was amplified and chromosomally dispersed subsequent to the divergence of orangutan from African apes but before the trichotomous divergence of human, chimpanzee, and gorilla 5-8 million years ago. The appearance of a transcriptionally active and chromosomally dispersed multigene KGF family may have implications in the evolution of the great apes and humans. PMID- 1409638 TI - Characterization and mutagenesis of the gene encoding the A49 subunit of RNA polymerase A in Saccharomyces cerevisiae. AB - The gene encoding the 49-kDa subunit of RNA polymerase A in Saccharomyces cerevisiae has been identified by formation of a hybrid enzyme between the S. cerevisiae A49 subunit and Saccharomyces douglasii subunits based on a polymorphism existing between the subunits of RNA polymerase A in these two species. The sequence of the gene reveals a basic protein with an unusually high lysine content, which may account for the affinity for DNA shown by the subunit. No appreciable homology with any polymerase subunits, enzymes, or transcription factors is found. Complete deletion of the single-copy RPA49 gene leads to viable but slowly growing colonies. Insertion of the HIS3 gene halfway into the RPA49 coding region results in synthesis of a truncated A49 subunit that is incorporated into the polymerase. The truncated and wild-type subunits compete equally for assembly in the heterozygous diploid, although the wild type is phenotypically dominant. PMID- 1409639 TI - Functional expression of zeaxanthin glucosyltransferase from Erwinia herbicola and a proposed uridine diphosphate binding site. AB - Erwinia herbicola, a nonphotosynthetic bacterium, is yellow colored due to the accumulation of unusually polar carotenoids, primarily mono- and diglucosides of zeaxanthin. We have cloned and expressed the gene for the enzyme that catalyzes the glucosylation of zeaxanthin. The enzyme has an apparent molecular mass of 45 kDa on an SDS/polyacrylamide gel, which is consistent with its calculated molecular mass. In vitro enzymatic activity was demonstrated using UDP [14C]glucose and zeaxanthin as substrates. The product zeaxanthin diglucoside and its intermediate monoglucoside were identified by thin layer chromatography. The optimum pH and temperature ranges of the enzyme are 7.0-7.5 and 32-37 degrees C, respectively. A hydropathy plot indicates no apparent membrane-spanning regions, and biochemical experiments suggest that the enzyme is weakly membrane associated. The amino acid sequence derived from the zeaxanthin glucosyltransferase gene shows a small region of high similarity with other glucuronosyl- and glucosyltransferases that use either UDP-activated glucuronic acid or a sugar as one of their substrates. Based on these similarities, we propose that this conserved sequence is part of the UDP binding site. PMID- 1409640 TI - Release of N2,3-ethenoguanine from chloroacetaldehyde-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II. AB - The human carcinogen vinyl chloride is metabolized in the liver to reactive intermediates which form N2,3-ethenoguanine in DNA. N2,3-Ethenoguanine is known to cause G----A transitions during DNA replication in Escherichia coli, and its formation may be a carcinogenic event in higher organisms. To investigate the repair of N2,3-ethenoguanine, we have prepared an N2,3-etheno[14C]guanine containing DNA substrate by nick-translating DNA with [14C]dGTP and modifying the product with chloroacetaldehyde. E. coli 3-methyladenine DNA glycosylase II, purified from cells which carry the plasmid pYN1000, releases N2,3-ethenoguanine from chloroacetaldehyde-modified DNA in a protein- and time-dependent manner. This finding widens the known substrate specificity of glycosylase II to include a modified base which may be associated with the carcinogenic process. Similar enzymatic activity in eukaryotic cell might protect them from exposure to metabolites of vinyl chloride. PMID- 1409641 TI - Cloning of an apparent splice variant of the rat N-methyl-D-aspartate receptor NMDAR1 with altered sensitivity to polyamines and activators of protein kinase C. AB - Molecular cloning identified complementary DNA species, from a rat ventral midbrain library, encoding apparent splice variants of the N-methyl-D-aspartate (NMDA) receptor NMDAR1 (which we now term NR1a). Sequencing revealed that one variant, NR1b, differs from NR1a by the presence of a 21-amino acid insert near the amino end of the N-terminal domain and by an alternate C-terminal domain in which the last 75 amino acids are replaced by an unrelated sequence of 22 amino acids. NR1b is virtually identical to NR1a in the remainder of the N- and C terminal domains, at the 5' and 3' noncoding ends, and within the predicted transmembrane domains and extracellular and cytoplasmic loops. These findings suggest that the two forms of the receptor arise by differential splicing of a transcript from the same gene. Sequencing of other clones indicates the existence of a third variant, NR1c, identical to NR1b in its C terminus but lacking the N terminal insert. NR1b RNA injected into Xenopus oocytes generated functional homomeric NMDA channels with electrophysiological properties distinct from those of NR1a homomeric channels. NR1b channels exhibited a lower apparent affinity for NMDA and for glutamate. NR1b channels exhibited a lower affinity for D-2-amino-5 phosphonovaleric acid and a higher affinity for Zn2+. The two receptor variants showed nearly identical affinities for glycine, Mg2+, and phencyclidine. Spermine potentiation of NMDA responses, prominent in oocytes injected with rat forebrain message, was also prominent for NR1a receptors, but was greatly reduced or absent for NR1b receptors. Treatment with the protein kinase C activator phorbol 12 myristate 13-acetate potentiated NMDA responses in NR1b-injected oocytes by about 20-fold; potentiation of NMDA responses in NR1a-injected oocytes was much less, about 4-fold. These findings support a role for alternate splicing in generating NMDA channels with different functional properties. PMID- 1409642 TI - Peptoids: a modular approach to drug discovery. AB - Peptoids, oligomers of N-substituted glycines, are described as a motif for the generation of chemically diverse libraries of novel molecules. Ramachandran-type plots were calculated and indicate a greater diversity of conformational states available for peptoids than for peptides. The monomers incorporate t-butyl-based side-chain and 9-fluorenylmethoxy-carbonyl alpha-amine protection. The controlled oligomerization of the peptoid monomers was performed manually and robotically with in situ activation by either benzotriazol-1 yloxytris(pyrrolidino)phosphonium hexafluorophosphate or bromotris(pyrrolidino)phosphonium hexaflurophosphate. Other steps were identical to peptide synthesis using alpha-(9-fluorenylmethoxycarbonyl)amino acids. A total of 15 monomers and 10 oligomers (peptoids) are described. Preliminary data are presented on the stability of a representative oligopeptoid to enzymatic hydrolysis. Peptoid versions of peptide ligands of three biological systems (bovine pancreatic alpha-amylase, hepatitis A virus 3C proteinase, and human immunodeficiency virus transactivator-responsive element RNA) were found with affinities comparable to those of the corresponding peptides. The potential use of libraries of these compounds in receptor- or enzyme-based assays is discussed. PMID- 1409643 TI - Cloning and chromosomal mapping of a human immunodeficiency virus 1 "TATA" element modulatory factor. AB - A critical regulatory element in many promoters transcribed by RNA polymerase II is the "TATA" box, which is located 25-30 nucleotides upstream of the transcription initiation site. TFIID is a biochemically defined HeLa cell nuclear fraction containing a transcription factor activity that binds specifically to the TATA box and is critical in determining both basal and regulated promoter activity. Recently, the gene for a TATA-binding protein was cloned and found to bind to various TATA elements and to substitute for TFIID in stimulating basal gene expression in in vitro transcription systems. However, it is possible that additional cellular factors can bind to the TATA element and influence the level of gene expression. By using lambda gt11 expression cloning with oligonucleotides corresponding to the human immunodeficiency virus 1 TATA element, we report the identification of a cellular protein with a calculated molecular mass of 123 kDa that we designate TATA element modulatory factor (TMF). TMF binds to the human immunodeficiency virus 1 TATA element in gel-retardation assays and inhibits activation of the viral long terminal repeat by the TATA-binding protein in in vitro transcription assays. TMF contains leucine-zipper amino acid motifs and exhibits homology in its DNA binding domain with the phage-encoded DNA binding protein Ner. Chromosomal mapping localizes the TMF gene to human chromosome 3p12 p21, which is a site of frequent rearrangements in lung and renal carcinomas. Thus, TMF is a transcription factor that likely regulates the expression of both viral and cellular genes. PMID- 1409644 TI - Nitric oxide stimulates auto-ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase. AB - Nitric oxide generation in brain cytosolic fractions markedly enhances ADP ribosylation of a single 37-kDa protein. By utilizing a biotinylated NAD and avidin affinity chromatography, we purified this protein. Partial amino acid sequencing establishes its identity as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This is further confirmed by detection of GAPDH enzymatic activity in the purified 37-kDa protein. GAPDH is ADP-ribosylated in the absence of brain extract. This auto-ADP-ribosylation is enhanced by nitric oxide generation. ADP ribosylation appears to involve the cysteine where NAD interacts with GAPDH so that ADP-ribosylation likely inhibits enzymatic activity. Such inhibition may play a role in nitric oxide-mediated neurotoxicity. PMID- 1409645 TI - Both purified human 1,N6-ethenoadenine-binding protein and purified human 3 methyladenine-DNA glycosylase act on 1,N6-ethenoadenine and 3-methyladenine. AB - We previously described a protein, isolated from human tissues and cells, that bound to a defined double-stranded oligonucleotide containing a single site specifically placed 1,N6-ethenoadenine. It was further demonstrated that this protein was a glycosylase and released 1,N6-ethenoadenine. We now find that this enzyme also releases 3-methyladenine from methylated DNA and that 3-methyladenine DNA glycosylase behaves in the same manner, binding to the ethenoadenine containing oligonucleotide and cleaving both ethenoadenine and 3-methyladenine from DNA containing these adducts. The rate and extent of glycosylase activities toward the two adducts are similar. PMID- 1409646 TI - Spontaneous insertion of polypeptide chains into membranes: a Monte Carlo model. AB - The Monte Carlo dynamics method was used to examine the process of protein insertion into model cell membranes. The water and lipid environments were taken into account via an effective medium approximation based on coordinate-dependent hydrophobic and hydrogen bond potentials. The polypeptide chain was represented in a full-backbone atom representation as a chain of diamond lattice vectors. The simulations support the idea that to a good approximation insertion may be depicted as a spontaneous thermodynamic process. The mechanism of membrane insertion of a simple lattice protein chain exhibits many features of theoretical predictions and is in good accord with experimental data. In the model, insertion begins with adsorption of the chain onto the interface, followed by the formation of helical fragments. These fragments, having partially saturated internal hydrogen bonds, can be transported into the lipid phase and then form transbilayer structures. PMID- 1409647 TI - Activation of potassium channels: relationship to the heat shock response. AB - We examined the possibility that whole cell currents are involved and possibly trigger the response of mammalian cells to heat shock. Heat-sensitive cells from a radiation-induced fibrosarcoma (RIF-1) and heat-resistant variants (TR-4, TR-5) were heated at 45 degrees C for 3-30 min. We observed induction of voltage dependent currents after heating in the heat-resistant cells. These currents decayed to nonmeasurable levels over a period of 6 h. In RIF-1 cells, however, voltage-dependent currents were detectable during heating only; these currents then decayed rapidly. Tetraethylammonium (TEA) cations blocked the currents; changing the concentration of extracellular K+ modified the current-voltage (I-V) relationship. These currents, therefore, resulted from the activation of voltage dependent K+ channels. Addition of TEA during heating sensitized TR-4 cells to heat but had no effect on the heat response of the RIF-1 cells. Continuous exposure of the RIF-1 cells to 2% (vol/vol) dimethyl sulfoxide (DMSO) for 7 days induced the expression of additional functional, voltage-dependent K+ channels; these gave rise to currents that were measurable after heating. In parallel, these cells became heat resistant. Addition of TEA to DMSO-treated cells blocked channels and returned the heat response almost to the pre-DMSO levels. Our data show a correlation between heat resistance and expression of K+ channels. Because resistance to heat very likely relates to the heat shock response, our data suggest that activation of channels may be a very early event in initiation of the heat shock response. PMID- 1409648 TI - Grammatical model of the regulation of gene expression. AB - Based on a formal proof that justifies the search for generative grammars in the study of gene regulation, a linguistic formalization of an exhaustive data base of Escherichia coli sigma 70 promoters and their regulatory binding sites has been initiated. The grammar presented here generates all the arrays of the collection plus those that are predicted as consistent with the principles of regulation of sigma 70 promoters. "Systems of regulation," sets of regulatory sites that collaborate in a mechanism of regulation, are represented by means of syntactic categories. A small set of phrase structure rules restricted by an X bar principle and by a hierarchical, c-command relation generates a representation of arrays of sites of regulation where the selection of the protein(s) identifying the system(s) of regulation occurs. Based on the features of the proteins, optional duplicated proximal and remote sites are generated by means of transformational rules. Consistency with the data, the predictions that the grammar generates, and important similarities and differences with some aspects of the generative theory of natural language are discussed. PMID- 1409649 TI - Dominant negative selection of heterologous genes: isolation of Candida albicans genes that interfere with Saccharomyces cerevisiae mating factor-induced cell cycle arrest. AB - We have used a genomic library of Candida albicans to transform Saccharomyces cerevisiae and screened for genes that act similarly to dominant negative mutations by interfering with pheromone-mediated cell cycle arrest. Six different plasmids were identified from 2000 transformants; four have been sequenced. One gene (CZF1) encodes a protein with structural motifs characteristic of a transcription factor. A second gene (CCN1) encodes a cyclin homologue, a third (CRL1) encodes a protein with sequence similarity to GTP-binding proteins of the RHO family, and a fourth (CEK1) encodes a putative kinase of the ERK family. Since CEK1 confers a phenotype similar to that of the structurally related S. cerevisiae gene KSS1 but cannot complement a KSS1 defect, it is evident that dominant negative selection can identify proteins that complementation screens would miss. Because dominant negative mutations exert their influence even in wild-type strain backgrounds, this approach should be a general method for the analysis of complex cellular processes in organisms not amenable to direct genetic analysis. PMID- 1409650 TI - Complementation of a red-light-indifferent cyanobacterial mutant. AB - Many cyanobacteria alter their phycobilisome composition in response to changes in light wavelength in a process termed complementary chromatic adaptation. Mutant strains FdR1 and FdR2 of the filamentous cyanobacterium Fremyella diplosiphon are characterized by aberrant chromatic adaptation. Instead of adjusting to different wavelengths of light, FdR1 and FdR2 behave as if they are always in green light; they do not respond to red light. We have previously reported complementation of FdR1 by conjugal transfer of a wild-type genomic library. The complementing DNA has now been localized by genetic analysis to a region on the rescued genomic subclone that contains a gene designated rcaC. This region of DNA is also able to complement FdR2. Southern blot analysis of genomic DNA from FdR1 and FdR2 indicates that these strains harbor DNA insertions within the rcaC sequence that may have resulted from the activity of transposable genetic elements. The predicted amino acid sequence of RcaC shares strong identity to response regulators of bacterial two-component regulatory systems. This relationship is discussed in the context of the signal-transduction pathway mediating regulation of genes encoding phycobilisome polypeptides during chromatic adaptation. PMID- 1409651 TI - Role of the basic amino acid cluster and Glu-23 in pyrimidine dimer glycosylase activity of T4 endonuclease V. AB - T4 endonuclease V [endodeoxyribonuclease (pyrimidine dimer); deoxyribonuclease (pyrimidine dimer), EC 3.1.25.1] initiates repair of damaged DNA by hydrolysis of the N-glycosyl bond at the 5' side of a pyrimidine photodimer in double-stranded DNA. To study one of the active sites of T4 endonuclease V, systematic site directed mutagenesis was performed on the synthetic T4 endonuclease V gene, in parallel with three-dimensional structure analysis by x-ray crystallography. The mutant proteins were evaluated for DNA glycosylase activity using an oligonucleotide duplex (14-mer) containing a single thymidine dimer as a substrate. Replacement of either Glu-23 with glutamine or asparatic acid or Arg-3 with glutamine completely abolished DNA glycosylase activity. Mutation of Arg-3 to lysine or of Arg-26 to glutamine or lysine in a basic amino acid cluster caused serious defects in DNA glycosylase activity, which are reflected in the increases in Km and decreases in kcat of DNA glycosylase activity. On the other hand, substitutions of lysine for Arg-22 or of glutamine for Arg-117 or Lys-121 resulted in increases in the Km value. The completely inactive mutant proteins, E23Q and R3Q, in which glutamine was substituted for Glu-23 and Arg-3, respectively, were further investigated by CD spectroscopy for their ability to bind the oligonucleotide substrate. It was found that the E23Q protein retained specific substrate-binding ability, whereas the R3Q protein did not. These results indicate that Glu-23 plays an important role in catalysis of the DNA glycosylase reaction, and that Arg-3 is a crucial residue for substrate binding. In addition, Arg-22, Arg-26, Arg-117, and Lys-121 in the basic amino acid cluster also participate in substrate binding. We conclude that the basic amino acid cluster in T4 endonuclease V is an essential structure for DNA glycosylase activity. PMID- 1409652 TI - Three-dimensional structure of two crystal forms of FabR19.9 from a monoclonal anti-arsonate antibody. AB - The three-dimensional structure of FabR19.9 from a well-characterized anti-p azobenzenearsonate monoclonal antibody has been determined by x-ray diffraction techniques in two crystalline forms (I and II) to a resolution of 2.8 and 2.7 A, respectively. Essentially the same tertiary and quaternary structure of the Fab is observed in the two forms. The major difference resides in the intermolecular contacts, which are interpreted to favor an irreversible transition from the metastable form I to the more stable form II. The third complementarity determining region of the heavy chain (H3) folds back over the combining site and requires rearrangement for hapten binding. This dynamic requirement on H3 is consistent with its mobility in the structure and can explain hapten binding to an otherwise inaccessible antibody combining site. PMID- 1409653 TI - Small amino acid changes in the V3 hypervariable region of gp120 can affect the T cell-line and macrophage tropism of human immunodeficiency virus type 1. AB - Human immunodeficiency virus type 1 (HIV-1) strains display a high degree of heterogeneity in their biological properties that correlate with in vivo pathogenesis of the virus. We previously demonstrated that overlapping regions encompassing the third hypervariable domain (V3), within the envelope glycoprotein gp120 determine the tropisms of HIV-1 for T-cell lines and primary macrophages. Studies with mutant viruses carrying one or more amino acid substitutions in the V3 loop have now identified this hypervariable domain as a major determinant for these cellular host range properties. Three to five amino acid changes in this domain, but rarely a single amino acid substitution, can confer macrophage tropism and alter T-cell-line tropism. These findings emphasize the effect on cell tropism of small amino acid differences in the viral envelope and suggest that the overall conformation of the V3 loop plays the major role in determining the ability of HIV-1 to infect T-cell lines and primary macrophages. PMID- 1409654 TI - Increased expression of beta-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage. AB - Despite increasing evidence for a pathogenetic role for the beta-amyloid precursor protein (beta APP) in Alzheimer disease, the physiological function of the protein remains unclear. The expression of the neural-specific isoform containing 695 amino acids, beta APP695, is consistent with a role for the protein in neuronal development. In this study, we analyzed the expression of beta APP during the retinoic acid-induced neuronal differentiation of P19 murine embryonal carcinoma cells. Northern blot and RNase protection analyses show a selective increase in beta APP695 expression, concomitant with the morphologic differentiation of P19-derived neurons. Moreover, the time course of increase observed for the beta APP695 mRNA is paralleled by other neuronal-specific transcripts. A similar increase in beta APP695 is observed at the protein level. Furthermore, we show that levels of beta APP695 protein progressively increase during the in vitro differentiation of primary hippocampal neurons. The finding that beta APP695 increases selectively and progressively during neuronal differentiation in two different cell culture systems suggests that this isoform has an important cellular function during this process in the brain. Unlike beta APP in most peripheral cell types, the increased levels of beta APP found in terminally differentiated neuronal cells are not processed in significant amounts by secretory cleavage. Thus, differentiation of neurons is accompanied by increased beta APP695 expression and membrane retention of the protein as intact, full-length molecules that could serve as potential substrates for amyloidogenesis. PMID- 1409655 TI - Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. AB - Specific sensory input has profound transient and long-lasting effects on the function of corresponding sensory cortical areas both during development and in adulthood. To study whether neurotrophic factors might play a role in such processes, we investigated the effects of light on the nerve growth factor and brain-derived neurotrophic factor (BDNF) mRNA levels in rat visual cortex. Keeping adult rats in the dark or preventing normal activity of retinal ganglion cells by intraocular injection of tetrodotoxin significantly decreased the levels of BDNF mRNA in the visual cortex but not in other cortical areas. Exposure to light after a period in darkness rapidly restored the mRNA to control levels. These alterations in visual input had no effect on nerve growth factor mRNA. The mRNA of trkB, the putative signal-transducing receptor unit for BDNF, was also decreased in darkness, although less than BDNF mRNA. BDNF mRNA levels increased in the visual cortex of newborn rats after eye-opening. This increase is retarded, although not completely abolished, by rearing the pups in darkness. Thus, the levels of BDNF mRNA are rapidly regulated by sensory input during development and in adulthood. BDNF may therefore play an important role in formation and in activity-dependent modulation of specific connections in the visual cortex. PMID- 1409656 TI - Cell cycle-dependent localization of casein kinase I to mitotic spindles. AB - Casein kinase I (CKI) is a class of protein kinases ubiquitous to all eukaryotic cells. Recently, cDNA clones encoding several bovine CKI isoforms have been sequenced that show high sequence identity to the HRR25 gene product of the budding yeast Saccharomyces cerevisiae; HRR25 is required for normal cellular growth, nuclear segregation, DNA repair, and meiosis. We have raised polyclonal antibodies to a human erythroid 34-kDa CKI and have sequenced a portion of this kinase. The amino acid sequence identifies the CKI as the alpha-CKI isoform, which is 62% identical to the HRR25 protein kinase. By use of immunofluorescence, the alpha-CKI has been localized to vesicular cytosolic structures and to the centrosome in interphase cells. As cells progress into mitosis, centrospheric staining increases and, in mitosis, alpha-CKI associates with kinetochore fibers. This localization suggests that alpha-CKI, like HRR25, plays a role in the segregation of chromosomes during mitosis and may be cell cycle-regulated both in humans and in yeast. PMID- 1409657 TI - Reduction of arsenate to arsenite by the ArsC protein of the arsenic resistance operon of Staphylococcus aureus plasmid pI258. AB - The arsenic resistance operon of Staphylococcus aureus plasmid pI258 consists of three genes, arsR (encoding the repressor regulatory protein), arsB (the determinant of the membrane efflux protein that confers resistance by pumping arsenic from the cells), and arsC (the small gene whose protein product is required for arsenate resistance only, not for arsenite resistance). ArsC has now been shown to be an arsenate reductase, converting intracellular arsenate [As(V)] to arsenite [As(III)], which is then exported from the cells by an energy dependent efflux process. The arsenate reductase activity was found in the soluble cytoplasmic fraction in Escherichia coli (and not associated with the periplasmic fraction or the sedimentable cell envelope). Purified ArsC protein coupled in vitro with thioredoxin plus dithiothreitol (but not 2-mercaptoethanol or reduced glutathione) to reduce arsenate to arsenite. PMID- 1409658 TI - Regulation of the yeast DNA replication genes through the Mlu I cell cycle box is dependent on SWI6. AB - In Saccharomyces cerevisiae, at least 17 DNA replication genes are coordinately expressed at the G1/S boundary during the cell cycle. All of these genes have the DNA sequence element ACGCGT in their 5' upstream regulatory regions. This sequence has been shown to be essential for periodic expression of the POL1, CDC9, and TMP1 genes. The cyclin (CLN1 and CLN2) and HO genes are another subset of genes that are expressed with the same timing as the DNA replication genes. Their periodic expression requires the participation of two well-characterized transcriptional activators: the SWI4 and SWI6 gene products. In this study, we present evidence that SWI6 contributes to the regulation of DNA replication genes as well. Surprisingly, a preferential requirement for SWI6 over SWI4 is observed in our studies of ACGCGT-dependent reporter gene expression in vivo. This selectivity has not been observed for the other G1/S genes. Correlating with the in vivo results, protein-DNA complexes formed in vitro on multimeric ACGCGT elements are either abolished or reduced in swi6 delta deletion mutants. PMID- 1409659 TI - The repressor MDBP-2 is a member of the histone H1 family that binds preferentially in vitro and in vivo to methylated nonspecific DNA sequences. AB - MDBP-2 is a repressor that binds preferentially to methylated DNA. Peptides derived from MDBP-2 were sequenced. The sequences of the two peptides, KPAGPS VTELITK and ALAAGGYDVEK, are identical to those found in the chicken histone H1 core protein. In SDS/polyacrylamide gels MDBP-2 has an apparent molecular mass of 21 kDa, and antibodies directed against calf thymus total histone H1 cross-react with MDBP-2. The preferential binding of affinity-purified MDBP-2 to methylated DNA is not sequence-specific but requires a minimum length of 30 base pairs and one pair of symmetrically methylated (i.e., methylated on both strands) CpG dinucleotides. As previously shown, there is a decrease in the binding activity of MDBP-2 to methylated DNA upon estradiol treatment. Immunoblots show that upon estradiol treatment the amount of immunocrossreacting MDBP-2 protein remains unchanged. MDBP-2 enables another protein to bind DNA which by itself does not bind methylated DNA. Ultraviolet crosslinking and selective immunoadsorption assays with anti-histone H1 antibodies show that in vivo MDBP-2 preferentially binds to the methylated repressed vitellogenin gene. It is concluded that MDBP-2 may participate in the long-term silencing of genes (formation of heterochromatin) through selective binding to methylated DNA. PMID- 1409660 TI - Retroviral analysis of cardiac morphogenesis: discontinuous formation of coronary vessels. AB - Cellular progenitors of the coronary vasculature are believed to enter the chicken heart during epicardial morphogenesis between stages 17 and 27 (days 3-5) of egg incubation. To trace cells which give rise to the coronary arteries in vivo, we applied retroviral cell tagging procedures and analyzed clonal populations of vascular smooth muscle, endothelium, and connective tissue in the hearts of post-hatch chickens. Our data provide direct proof that (i) vascular smooth muscle progenitors begin to enter the heart at stage 17, substantially after the heart begins propulsive contractions; (ii) cardiac myocytes, vascular smooth muscle, perivascular fibroblasts, and coronary endothelial cells all derive from independent precursors when these cells migrate into the heart; (iii) endothelial cells of the coronary vessels have a different clonal origin than endothelial cells of the endocardium; (iv) coronary arteries form by the coalescence of discontinuous colonies (i.e., in situ vasculogenesis), each derived from a founder cell tagged at the time of retroviral injection (stages 17 18); and (v) coronary arteries contain discrete segments composed of "polyclones." These studies indicate the feasibility of gene targeting to coronary progenitors through the use of recombinant retroviruses. PMID- 1409661 TI - Primary electron transfer kinetics in bacterial reaction centers with modified bacteriochlorophylls at the monomeric sites BA,B. AB - The primary electron transfer has been investigated by femtosecond time-resolved absorption spectroscopy in two chemically modified reaction centers (RC) of Rhodobacter sphaeroides, in which the monomeric bacteriochlorophylls BA and BB have both been exchanged by 13(2)-hydroxybacteriochlorophyll a or [3-vinyl]-13(2) hydroxybacteriochlorophyll a. The kinetics of the primary electron transfer are not influenced by the 13(2)-hydroxy modification. In RCs containing [3-vinyl] 13(2)-hydroxybacteriochlorophyll a the primary rate is reduced by a factor of 10. PMID- 1409662 TI - Prevention of autoimmune insulitis in nonobese diabetic mice by expression of major histocompatibility complex class I Ld molecules. AB - Nonobese diabetic (NOD) mice spontaneously develop a T-cell-mediated autoimmune disease that is similar in many respects to insulin-dependent diabetes mellitus in humans. NOD mice were shown to express major histocompatibility complex class I Kd and Db antigens. To examine the possible involvement of major histocompatibility complex class I molecules in the development of autoimmune insulitis, we attempted to express a different type of class I molecule in NOD mice by crossing C57BL/6 mice transgenic for the class I Ld gene with NOD mice. The backcross progeny expressed the Ld antigen on the peripheral blood lymphocytes at a level comparable with that of the BALB/c mice. The cell surface expression of endogenous class I and class II antigens on the peripheral blood lymphocytes was not affected. Analysis of these mice revealed that the expression of the class I Ld antigen significantly reduced the incidence of insulitis at 20 weeks of age. In situ hybridization of a biotinylated probe on mouse chromosomes showed that the Ld transgene was located in the E area of chromosome 6 with which no genetic linkage to insulin-dependent diabetes mellitus was demonstrated. These results suggest that the NOD-type class I molecules are involved in the development of insulitis in NOD mice. PMID- 1409663 TI - Birth and migration of neurons in the central posterior/prepacemaker nucleus during adulthood in weakly electric knifefish (Eigenmannia sp.). AB - In contrast to mammals, fish maintain their capacity to generate neurons in the central nervous system even during adulthood for prolonged periods of life. By employing immunohistochemical, autoradiographic, and electron microscopic techniques, we studied such a postnatal neurogenesis within the complex of the central posterior/prepacemaker nucleus (CP/PPn) in knifefish (Eigenmannia sp.), a weakly electric teleost. The CP/PPn is a bilateral cluster of neurons in the thalamus. It controls frequency modulations of the electric organ discharge as they are used during social interactions. In the CP/PPn region adjacent to the wall of the third ventricle ("ventricular zone"), cells are born continuously and at high rates. They undergo multiple cell divisions before differentiating into neurons. Concomitant with this development, the newborn neurons migrate toward lateral regions of the CP/PPn. In the course of this lateral migration, they appear to acquire immunological and morphological characteristics that are typical for mature CP/PPn neurons. We hypothesize that at least some of the newly generated cells develop finally into functional CP/PPn neurons. PMID- 1409664 TI - Decreased choline acetyltransferase mRNA expression in the nucleus basalis of Meynert in Alzheimer disease: an in situ hybridization study. AB - The subnormal choline acetyltransferase (ChoAcTase) activity in the cerebral cortex of patients with Alzheimer disease (AD) is thought to originate from the loss of cholinergic neurons in the nucleus basalis of Meynert (nbM). To examine possible changes in the functional activity of the remaining cholinergic neurons in the nbM of patients with AD, the level of expression of ChoAcTase mRNA was evaluated. A procedure for double-labeling cholinergic neurons to detect ChoAcTase mRNA and the corresponding protein in the same cell was developed, taking advantage of an anti-ChoAcTase antibody and the recently isolated cDNA complementary to a sequence of the human ChoAcTase mRNA. In the study of three controls and four patients with AD, the presence of both ChoAcTase mRNA and protein was observed in the same large neurons in both nbM and putamen. Specificity of in situ hybridization was further supported by the absence of neuronal staining with a sense probe. In AD patients a subnormal level of expression of ChoAcTase mRNA per cholinergic cell was detected in the nbM but not in the putamen. Our data support the hypothesis that expression of ChoAcTase mRNA might be down-regulated in the surviving cholinergic neurons in the nbM of patients with AD, raising the possibility of functional restoration by stimulating ChoAcTase synthesis. PMID- 1409665 TI - Farnesylcysteine, a constituent of the alpha and beta subunits of rabbit skeletal muscle phosphorylase kinase: localization by conversion to S-ethylcysteine and by tandem mass spectrometry. AB - The primary structure of the alpha and beta subunits of phosphorylase kinase reveals that both proteins contain a carboxyl-terminal CA1A2X motif (where C is cysteine, A1 and A2 are aliphatic amino acids, and X is an uncharged amino acid), the recognition signal for a protein polyisoprenyltransferase. The product, a polyisoprenylated cysteine, can be detected by phenylthiocarbamoylamino acid analysis and by microsequencing following conversion to S-ethylcysteine. Mass spectrometry confirms a covalently linked farnesyl residue in both subunits. Tandem mass spectrometry localizes these modifications at the cysteine residues present in the carboxyl-terminal CAMQ and CLVS sequences of the alpha and beta subunits, respectively. Membrane association of phosphorylase kinase, probably mediated by these farnesyl residues, is discussed. PMID- 1409666 TI - Characterization of the genes encoding phycoerythrin in the red alga Rhodella violacea: evidence for a splitting of the rpeB gene by an intron. AB - The phycobilisome of the eukaryotic unicellular red alga Rhodella violacea presents in some respects an organization that is intermediate between those of the homologous counterparts found in cyanobacteria (the putative chloroplast progenitor) and more advanced, pluricellular red algae. This suggests evolutionary relationships that we investigated at the genome level. The present work describes the sequences of two rhodophytan phycobilisome genes, rpeA and rpeB. These chloroplast genes encode the alpha and beta subunits of phycoerythrin, the major component of the light-harvesting antennae and one of the most abundant cellular proteins in these algae. The amino acid sequences deduced from both rpeA and rpeB present strong homologies with those previously reported for phycoerythrin subunits of cyanobacteria, rhodophyta, and cryptomonads. The main difference with the corresponding cyanobacterial genes was the unexpected occurrence of an intervening sequence that split rpeB into two exons. This intervening sequence presents characteristics of group II introns but lacks several structural domains. Transcriptional analyses showed that the two rpe genes are cotranscribed and that the major RNA species detected corresponds to a mature mRNA lacking the intron. As the phycobiliproteins form a group of closely related polypeptides in cyanobacteria and rhodophyta, the molecular events affecting the corresponding genes, such as the rpeB intron, may be a clue to elucidate some aspects of the molecular processes involved in the evolution of plastid genes. PMID- 1409667 TI - Structure of the host-specific toxins produced by the fungal pathogen Periconia circinata. AB - Four metabolites named peritoxins A and B and periconins A and B have been isolated together with the known metabolite circinatin from culture filtrates of the fungal pathogen Periconia circinata. Peritoxins A and B, which correspond to the P. circinata toxins Ia and IIa partially characterized in previous work, are selectively toxic to genotypes of Sorghum bicolor susceptible to the pathogen, whereas periconins A and B are biologically inactive. Combination of instrumental analysis and chemical degradation has led to structural assignments for each of the four compounds; only the configuration at some of the chiral centers remains undefined. Structural comparison suggests a precursor role for circinatin in the formation of the peritoxins and the periconins. PMID- 1409668 TI - Initiation of phi 29 DNA replication occurs at the second 3' nucleotide of the linear template: a sliding-back mechanism for protein-primed DNA replication. AB - Bacteriophage phi 29 DNA replication is initiated when a molecule of dAMP is covalently linked to a free molecule of the terminal protein, in a reaction catalyzed by the viral DNA polymerase. We demonstrate that single-stranded DNA molecules are active templates for the protein-primed initiation reaction and can be replicated by phi 29 DNA polymerase. Using synthetic oligonucleotides, we carried out a mutational analysis of the phi 29 DNA right end to evaluate the effect of nucleotide changes at the replication origin and to determine the precise initiation site. The results indicate that (i) there are no strict sequence requirements for protein-primed initiation on single-stranded DNA; (ii) initiation of replication occurs opposite the second nucleotide at the 3' end of the template; (iii) a terminal repetition of at least two nucleotides is required to efficiently elongate the initiation complex; and (iv) all the nucleotides of the template, including the 3' terminal one, are replicated. A sliding-back model is proposed in which a special transition step from initiation to elongation can account for these results. The possible implication of this mechanism for the fidelity of the initiation reaction is discussed. Since all the terminal protein containing genomes have some sequence reiteration at the DNA ends, this proposed sliding-back model could be extrapolable to other systems that use proteins as primers. PMID- 1409669 TI - Imaging of luciferase secretion from transformed Chinese hamster ovary cells. AB - The blue luminescence characteristic of the marine ostracod crustacean Vargula hilgendorfii is from a simple, but highly specific, enzyme-substrate reaction. Light is emitted by the oxidation of Vargula luciferin (substrate) by molecular oxygen, a reaction catalyzed by luciferase. Stable transformants of Chinese hamster ovary cells carrying the Vargula luciferase gene secreted luciferase from discrete sites on the cell surface, and this secretion could be monitored in real time by the bioluminescence produced by the secreted luciferase in the presence of Vargula luciferin by using an image-intensifying technique. Addition of anti Vargula luciferase IgG to the luminescing cells almost completely extinguished the luminescence, confirming that Vargula luciferase caused the luminescence. PMID- 1409670 TI - Reductive detoxification as a mechanism of fungal resistance to singlet oxygen generating photosensitizers. AB - Fungi that are resistant or sensitive to the singlet oxygen-generating toxin cercosporin were assayed for their ability to detoxify it by reduction. Cercosporin reduction was assayed microscopically by using bandpass filters to differentiate between fluorescence emission from cercosporin and reduced cercosporin. Hyphae of the resistant Cercospora and Alternaria species emitted a green fluorescence, indicative of reduced cercosporin. Hyphae of nonviable cultures and of cercosporin-sensitive fungi did not reduce cercosporin. Sensitive fungi occasionally reduced cercosporin when incubated with reducing agents that protect against cercosporin toxicity. Cercosporin could not be efficiently photoreduced in the absence of the fungus. Cercospora species were also resistant to eosin Y but were sensitive to rose bengal. Microscopic observation demonstrated that Cercospora species were not capable of reducing rose bengal but were capable of reducing eosin Y. These observations were supported by in vitro electrochemical measurements that revealed the following order with respect to ease of reduction: cercosporin >> eosin Y > rose bengal. The formal redox potential (E 0') of cercosporin at pH 7.5 was found to be -0.14 V vs. the normal hydrogen electrode. We conclude that Cercospora species protect themselves against cercosporin by the reduction and detoxification of the toxin molecule. PMID- 1409671 TI - Mutational analysis of the integrase protein of human immunodeficiency virus type 2. AB - Purified integrase protein (IN) can nick linear viral DNA at a specific site near the ends and integrate nicked viral DNA into target DNA. We have made a series of 43 site-directed point mutants of human immunodeficiency virus type 2 IN and assayed purified mutant proteins for the following activities: site-specific cleavage of viral DNA (donor cut), integration (strand transfer), and disintegration. In general, the different activities were similarly affected by the mutations. We found three mutations that (almost) totally abolished IN function: Asp-64-->Val, Asp-116-->Ile, and Glu-152-->Leu, whereas 25 mutations did not affect IN function. A few mutations affected the different activities differentially. Near the amino terminus a zinc finger-like sequence motif His Xaa3-His-Xaa20-30-Cys-Xaa2-Cys is present in all retroviral IN proteins. Two mutations in this region (His-12-->Leu and Cys-40-->Ser) strongly inhibited donor cut but had less effect on strand transfer. The central region of IN is most highly conserved between retroviral INs. Three mutants in this region (Asn-117- >Ile, Asn-120-->Leu, and Lys-159-->Val) were inhibited in strand transfer but were inhibited less strongly in donor cut. Mutation of Asn-120 (to glycine, leucine, or glutamate) resulted in changes in integration-site preference, suggesting that Asn-120 is involved in interactions with target DNA. We did not find a mutant in which one activity was lost and the others were unaffected, supporting the notion that IN has only one active site for the catalysis of donor cut and strand transfer. PMID- 1409672 TI - 1H-[13C] NMR measurements of [4-13C]glutamate turnover in human brain. AB - A limitation of previous methods for studying human brain glucose metabolism, such as positron emission tomography, is that metabolic steps beyond glucose uptake cannot be studied. Nuclear magnetic resonance (NMR) has the advantage of allowing the nondestructive measurement of 13C distribution in specific carbon positions of metabolites. In this study 1H-[13C] NMR spectroscopy in conjunction with volume localization was used to measure the rate of incorporation of 13C isotope from infused enriched [1-13C]glucose to human brain [4-13C]glutamate. In three studies C4 glutamate turnover time constants of 25, 20, and 17 min were measured in a 21-cm3 volume centered in the region of the visual cortex. Based on an analysis of spectrometer sensitivity the spatial resolution of the method can be improved to < 4 cm3. In conjunction with metabolic modeling and other NMR measurements this method can provide a measure of regional rates of the brain tricarboxylic acid cycle and other metabolic pathways. PMID- 1409673 TI - Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. AB - The legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular parasite. Its interaction with phagocytes has characteristics in common with several other intracellular parasites. Critical aspects of L. pneumophila intracellular multiplication are evasion of lysosomal host cell defenses and the presence of a nutritionally appropriate environment. Following phagocytosis, wild-type L. pneumophila multiply within a specialized phagosome which does not fuse with secondary lysosomes. Mutants which have lost the ability to grow within phagocytes no longer cause disease in animals, indicating that the capacity to multiply intracellularly is important for pathogenesis. One such mutant, 25D, has been shown to be defective in inhibiting phagosome-lysosome fusion. This phagolysosomal environment is not conducive to Legionella growth. We report the isolation of a region of the L. pneumophila genome (icm, intracellular multiplication) which restores the capacity of 25D to multiply in human macrophages. The complemented mutants also regain the capacity to interfere with phagosome-lysosome fusion and to cause lethal pneumonia in guinea pigs. PMID- 1409674 TI - Activation of expression of genes coding for extracellular matrix proteins in Tat producing glioblastoma cells. AB - The Tat protein of human immunodeficiency virus type 1 has been increasingly implicated in directly contributing to the disease AIDS by altering the expression of strategic cellular genes. In this study we demonstrate that the presence of the human immunodeficiency virus type 1 regulatory protein Tat is associated with a significant induction in the expression of certain protein components of the extracellular matrix in glial-derived cells. Northern blot analysis reveals that in cells expressing Tat there is a marked elevation in the steady-state RNA levels for fibronectin and types I and III collagen. Metabolic labeling of the Tat-producing cells demonstrates that this induction is also reflected at the level of protein synthesis. Transient transfection experiments indicate that the presence of Tat results in increased transcription of fibronectin and alpha I type I collagen promoters. Possible mechanisms for this phenomenon and their significance with regard to AIDS are discussed. PMID- 1409675 TI - Scanning tunneling microscopy imaging of Torpedo acetylcholine receptor. AB - The synaptic surface of the acetylcholine receptor in membranes from Torpedo californica electric organ has been imaged by scanning tunneling microscopy. The molecule appears pentameric, with one major and four minor protrusions rising above the surface, and these protrusions encompass a large central cavity. The outer diameter of the molecule is 69 +/- 10 A, while the diameter of the cavity, measured at the widest complete contour line delimiting the opening, is 26 +/- 7 A. The images and dimensions obtained are consistent with the structure determined from hybrid density maps obtained by x-ray diffraction and electron microscopy. Thus, scanning tunneling microscopy can be used to obtain overall dimensions and low-resolution structural features of the surface of a membrane embedded protein. PMID- 1409676 TI - Detection of transcripts for the receptor for macrophage colony-stimulating factor, c-fms, in murine osteoclasts. AB - Macrophage colony-stimulating factor (M-CSF), whose action is restricted to the cell populations of the mononuclear phagocyte system, has recently been found to be required for osteoclastogenesis and bone resorption. To investigate the cells involved in the action of M-CSF in these processes, expression of c-fms mRNA, encoding the M-CSF receptor, was studied by in situ hybridization. Paws from murine embryos and newborn mice, tibiae from 2-day-old animals, as well as isolated osteoclasts, were hybridized with a c-fms-specific RNA probe. In bone, c fms mRNA was detected only in cells at the late stages of osteoclastogenesis and in mature osteoclasts. The findings strengthen the relation between osteoclasts and the mononuclear phagocyte system. Furthermore, they suggest that M-CSF acts directly on osteoclast precursors and on mature osteoclasts during osteoclastogenesis. PMID- 1409677 TI - Symmetry in the mechanism of bacteriophage lambda integrative recombination. AB - During the strand-exchange events of bacteriophage lambda integration, pairs of phosphodiester bonds are broken and then rejoined to form novel DNA linkages. The reaction proceeds in vitro in the absence of an external energy source; the bond energy needed to rejoin broken strands of DNA must therefore be conserved during cleavage. Although some of this conservation involves a covalent intermediate between DNA and the recombinase Int, it is possible that such an intermediate is formed with only one of the two phosphodiesters. In such an asymmetric mechanism, the second phosphodiester would be attacked by a nucleophile that is exposed by cleavage of the first DNA strand. In contrast, a symmetric mechanism hypothesizes nucleophilic attack by Int on both phosphodiesters. We have distinguished these two mechanisms by removing potential nucleophiles from the integrative recombination reaction. Our data are inconsistent with an asymmetric mechanism. We conclude that during strand exchange both phosphodiesters proceed through a covalent protein-DNA intermediate. PMID- 1409678 TI - Plasmodium chabaudi p68 serine protease activity required for merozoite entry into mouse erythrocytes. AB - To define the role of malaria parasite enzymes during the process of erythrocyte invasion, we have developed an in vitro serum-free invasion assay of mouse erythrocytes by purified Plasmodium chabaudi merozoites. The sensitivity of a merozoite-specific serine protease (p68) to various inhibitors and the effect of these inhibitors on invasion indicate a crucial role for p68. The substrate specificity of the purified enzyme has been partially defined using fluorogenic peptides. Consistent with this, in vitro incubation of mouse erythrocytes with the merozoite enzyme led to the cleavage of band 3 protein. The possible implication of erythrocyte band 3 truncation for the successful entry of the merozoite into the erythrocyte is discussed. PMID- 1409679 TI - Distinct binding sites on HLA-DR for invariant chain and staphylococcal enterotoxins. AB - During biosynthesis, class II molecules of the major histocompatibility complex exist as complexes of the polymorphic alpha and beta chains in association with trimers of the invariant chain (Ii). The nonpolymorphic Ii contains sequences necessary for proper targeting of class II to endosomal compartments, where Ii is degraded. Ii also prevents the premature association of antigenic peptides with class II molecules. It is not known whether the effect of Ii on peptide binding extends to other ligands of class II, specifically exogenous superantigens. Cells expressing a mutant Ii molecule stably associated with HLA-DR at the cell surface were tested for their ability to interact with staphylococcal toxins. Most toxins (staphylococcal enterotoxins A-E and exfoliative toxin) were found to bind to cells expressing this alpha beta Ii complex with levels comparable to cells expressing only alpha beta chains at the cell surface. Cells expressing surface alpha beta Ii complexes stimulated polyclonal populations of peripheral blood T cells in association with these toxins. Binding of toxic shock syndrome toxin (TSST) and subsequent stimulation of T cells were reduced by the presence of the Ii. This reduction was not due to an alteration in the repertoire of T cells responding to TSST in the presence of Ii. Data from experiments with a T-cell clone suggest that interactions between class II molecules and T-cell antigen receptors occur during staphylococcal enterotoxin-mediated stimulation and that surface Ii does not interfere with such interactions. PMID- 1409680 TI - Dendritic field size and morphology of midget and parasol ganglion cells of the human retina. AB - The visual system of the macaque monkey has provided a useful model for understanding the neural basis of human vision, yet, there are few detailed comparisons of neural populations other than photoreceptors for the two species. Using intracellular staining in an in vitro preparation of the isolated and intact human retina, we have characterized the relationship of dendritic field size to retinal eccentricity for the two major ganglion cell classes, the midget and the parasol cells. We report three findings. (i) The difference in dendritic field diameter between the parasol and midget cells increases from a ratio of approximately 3:1 in the retinal periphery to approximately 10:1 at 3 degrees eccentricity, suggesting that human midget cells may outnumber parasol cells by as much as 30:1 in the central retina. (ii) The dendritic fields of human ON center parasol and midget cells are 30-50% larger in diameter than their OFF center counterparts, suggesting a distinct asymmetry in the human ON-OFF visual pathways. (iii) The dendritic fields of parasol cells, but not midget cells, are larger in humans than in macaques. The difference increases from approximately 20% in the retinal periphery to approximately 90% at 5 degrees eccentricity. This result predicts that the human parasol cells should show a lower resolving ability and an increased sensitivity to luminance contrast than their equivalents in the macaque. PMID- 1409681 TI - Quinolone binding to DNA is mediated by magnesium ions. AB - The binding of plasmid DNA to norfloxacin, a quinolone antibacterial agent, was investigated by fluorescence, electrophoretic DNA unwinding, and affinity chromatography techniques. The amount of quinolone bound to DNA was modulated by the concentration of Mg2+. No interaction was evident in the absence of Mg2+ or in the presence of an excess of Mg2+, whereas maximum binding was observed at a Mg2+ concentration of 1-2 mM. The experimental data can be fitted to the formation of three types of Mg adducts: a binary adduct with norfloxacin and Mg2+, a binary adduct with DNA and Mg2+, and a ternary adduct with quinolone, plasmid, and Mg2+. We propose a model for the ternary complex, in which Mg acts as a bridge between the phosphate groups of the nucleic acid and the carbonyl and carboxyl moieties of norfloxacin. Additional stabilization may arise from stacking interactions between the condensed rings of the drug and DNA bases (especially guanine and adenine), which may account for the preference exhibited by quinolones for single-stranded and purine-rich regions of nucleic acids. Other possible biochemical pathways of drug action are suggested by the observation that norfloxacin binds Mg2+ under conditions that are close to physiological. PMID- 1409682 TI - Conformational substates in azurin. AB - Azurin is a small blue copper protein in the electron transfer chain of denitrifying bacteria. It forms a photolabile complex with nitric oxide (NO) at low temperatures. We studied the temperature dependence of the ligand binding equilibrium and the kinetics of the association reaction after photodissociation over a wide range of temperature (80-280 K) and time (10(-6)-10(2) s). The nonexponential rebinding below 200 K is independent of the NO concentration and is interpreted as internal recombination. The rebinding can be modeled with the Arrhenius law by using a single preexponential factor of 6.3 x 10(8) s-1 and a Gaussian distribution of enthalpy barriers centered at 23 kJ/mol with a width of 11 kJ/mol. Above 200 K, a slower, exponential rebinding process appears. The dependence of the kinetics on the NO concentration characterizes this reaction as bimolecular rebinding. The binding kinetics of NO to azurin show impressive analogies to the binding of carbon monoxide to myoglobin. We conclude that conformational substates occur not only in heme proteins but also in proteins with different active sites and secondary structures. PMID- 1409683 TI - Sphingosine 1-phosphate, a specific endogenous signaling molecule controlling cell motility and tumor cell invasiveness. AB - Sphingosine 1-phosphate (Sph-1-P), the initial product of Sph degradation by Sph kinase, was shown to be a strong inhibitor of cell motility and phagokinesis of B16 melanoma and other types of cells at 10-100 nM concentration. It also inhibited "chemoinvasion" of tumor cells through a thick layer of Matrigel on a filter membrane. Such inhibitory effects were produced minimally or not at all by Sph, N-methyl derivatives of Sph, or other related sphingolipids and phospholipids. Sph-1-P did not inhibit cell proliferation or protein kinase C (PKC) activity, in contrast to Sph and N-methyl-Sph, which inhibit PKC activity and cell growth in general. Radiolabeled [3H]Sph and [14C]N-methyl-Sph were rapidly incorporated into B16 melanoma cells. However, [14C]N-methyl-Sph was not metabolically converted into other compounds, whereas [3H]Sph was efficiently converted within 10 min to Sph-1-P, followed by conversion to other sphingolipids and phospholipids. The inhibitory effect of Sph-1-P on cell motility and tumor cell invasiveness could be a specific phenomenon independent of PKC and other known transmembrane signaling mechanisms, based on an unknown mechanism. It may directly affect organizational assembly of actin filaments. Since exogenous Sph is rapidly converted into Sph-1-P, some reported effects of Sph may be ascribable to such conversion. PMID- 1409684 TI - Direct stimulation of immediate-early genes by intranuclear insulin in trypsin treated H35 hepatoma cells. AB - H35 hepatoma cells were treated with trypsin to abolish insulin binding and insulin-stimulated receptor kinase activity. Insulin was, however, internalized by fluid-phase endocytosis in trypsin-treated cells. Furthermore, nuclear accumulation of insulin was similar in control and trypsin-treated hepatoma cells. Northern blot analysis revealed insulin increased g33 and c-fos mRNA concentrations identically in control and trypsin-treated cells but had no effect on beta 2-microglobulin mRNA. Actinomycin D treatment prior to or after insulin addition demonstrated that insulin increased gene transcription and had no effect on mRNA degradation. These studies suggest that the accumulation of intact insulin in cell nuclei may be directly involved in the increased transcription of immediate-early genes. PMID- 1409685 TI - Myristoylation of the G alpha i2 polypeptide, a G protein alpha subunit, is required for its signaling and transformation functions. AB - GTPase-inhibiting mutations of the alpha subunit (alpha i2) of the G protein, Gi2, result in constitutive activation of alpha i2 signal transduction functions. GTPase-inhibited alpha i2 mutant polypeptides, referred to as gip2 oncoproteins, have glutamine-205 mutated to leucine (alpha i2Q205L). Expression of the alpha i2Q205L polypeptide inhibits adenylyl cyclase stimulation, constitutively activates p42 mitogen-activated protein kinase, and transforms Rat 1a fibroblasts. The alpha i2 polypeptides are N-terminal-myristoylated, but the function of myristoylation is unclear in alpha i2 signal transduction. We have tested the requirement for myristoylation on the ability of the alpha i2Q205L mutant polypeptide to constitutively regulate signal pathways and cell transformation. When expressed in Rat 1a cells, the nonmyristoylated alpha i2Q205L polypeptide is membrane associated but is unable to regulate adenylyl cyclase or p42 mitogen-activated protein kinase and does not induce cellular transformation. We conclude that myristoylation is absolutely necessary for alpha i2Q205L signal transduction and regulation of effector enzymes in the cell. PMID- 1409686 TI - Allosteric changes in the cAMP receptor protein of Escherichia coli: hinge reorientation. AB - The cAMP receptor protein (CRP) of Escherichia coli is a dimer of a two-domain subunit. It requires binding of cAMP for a conformational change in order to function as a site-specific DNA-binding protein that regulates gene activity. The hinge region connecting the cAMP-binding domain to the DNA-binding domain is involved in the cAMP-induced allosteric change. We studied the structural changes in CRP that are required for gene regulation by making a large number of single and double amino acid substitutions at four different positions in or near the hinge. To achieve cAMP-independent transcription by CRP, amino acid residues 138 (located within the hinge region) and 141 (located in the D alpha-helix adjacent to the hinge) must be polar. This need for polar residues at positions 138 and 141 suggests an interaction that causes the C and D alpha-helices to come together. As a consequence, the F alpha-helix is released from the D alpha-helix and can interact with DNA. At position 144 in the D alpha-helix and within interacting distances of the F alpha-helix, replacement of alanine by an amino acid with a larger side chain, regardless of its nature, allows cAMP independence. This result indicates that pushing against the F alpha-helix may be a way of making the helix available for DNA binding. We believe that the cAMP induced allosteric change involves similar hinge reorientation to adjust the C and D alpha-helices, allowing outward movement of the F alpha-helix. PMID- 1409687 TI - Isolation of DNA sequences deleted in lung cancer by genomic difference cloning. AB - To identify DNA sequences that are deleted in human lung cancer, genomic subtraction hybridization was used to construct plasmid libraries that are enriched for DNA sequences deleted in the small cell lung carcinoma cell line SK LC-17. The clones of the libraries contained predominantly single copy sequences, allowing direct screening of normal and tumor DNA by genomic Southern blotting. Of 150 clones tested, three independent clones (del-27, del-118, and del-109) were identified that specifically hybridized with normal human DNA but not with tumor DNA from the cell line SK-LC-17. The corresponding DNA sequences are localized on human chromosomes 5, 8, and X/Y. The DNA regions identified by del 109 and del-118 were also found to be deleted in several other lung carcinoma cell lines. Moreover, del-118 was deleted in a freshly isolated lymph node metastasis of a human lung adenocarcinoma. It is therefore reasonable to speculate that the identified clones are derived from independent genetic loci encoding potential tumor suppressor genes. PMID- 1409688 TI - Selective expression of human X chromosome-linked green opsin genes. AB - The human red and green photopigments are specified by genes on the long arm of the X chromosome (Xq28). In individuals with normal color vision, the locus was proposed to consist of a single red pigment gene upstream of one or more copies of green pigment genes. The presence of a single red pigment gene in the array was confirmed by demonstration of only one retinal mRNA transcript coding for the red opsin. In individuals with multiple green pigment genes, it is unknown whether all genes are expressed. We analyzed the sequence of red- and green specific mRNA from retinas of individuals with multiple green pigment genes in comparison with the corresponding genomic DNA sequences. The data showed that only a single green pigment gene is expressed. We therefore suggest that a locus control-like element, already known to be located 3.8 kilobases upstream of the transcription initiation site of the red pigment gene, allows transcription of only a single copy of the green pigment genes, probably the most proximal copy. This finding provides an explanation for the not-infrequent presence of 5' green red hybrid genes in individuals with normal color vision. Such hybrid genes are usually associated with defective color vision. We suggest that 5' green-red hybrid genes produce defective color vision only when their position in the gene array allows expression in the retinal cone cells. PMID- 1409689 TI - Asn177 in Escherichia coli thymidylate synthase is a major determinant of pyrimidine specificity. AB - The substrate preference of recombinant Escherichia coli thymidylate synthase (TS) has been altered from 2'-deoxyuridylate (dUMP) to 2'-deoxycytidylate (dCMP) by site-directed mutagenesis of the codon for Asn177, which was changed to aspartic acid. The side-chain amide of Asn177 forms hydrogen bonds with O4 and N3 of dUMP bound to the crystalline enzyme [Montfort, W. R., Perry, K. M., Fauman, E. B., Finer-Moore, J. S., Maley, G. F., Hardy, L., Maley, F. & Stroud, R. M. (1990) Biochemistry 29, 6964-6977]. This Asn is invariant in all natural sequences for TS known. The values of kcat for the mutant enzyme, TS(N177D), with dCMP and dUMP are, respectively, 0.09 and 0.002 times the value of kcat of wild type TS with dUMP as substrate. TS(N177D) turns over dCMP at 35 times its rate of dUMP turnover, whereas wild-type TS turns over dCMP at < 10(-5) of its rate of dUMP turnover. Thus Asn177 is a major determinant of the pyrimidine nucleotide specificity of TS. The mutant enzyme, like wild-type TS, forms a covalent complex with 5-fluoro-dUMP in the presence of 5,10-methylenetetrahydrofolate. TS(N177D) also has a newly acquired ability to be transiently inactivated by dUMP. This time-dependent inactivation requires the presence of methylenetetrahydrofolate and may be due to the accumulation of the enzyme in the form of a catalytic intermediate. The likely mechanistic basis for discrimination by TS between dUMP and dCMP is their differing requirements for charge stabilization during covalent catalysis. PMID- 1409690 TI - Circular dichroism and molecular modeling yield a structure for the complex of human immunodeficiency virus type 1 trans-activation response RNA and the binding region of Tat, the trans-acting transcriptional activator. AB - Transcription in the human immunodeficiency virus type 1 (HIV-1) retrovirus is regulated by binding the viral Tat protein (trans-acting transcriptional activator) to the trans-activation response (TAR) RNA sequence. Here, vacuum UV circular dichroism (VUV-CD) is used to study the structure of TAR and its complex with two peptide fragments that are important for Tat binding to TAR. The VUV-CD spectrum of TAR is typical of A-form RNA and is minimally perturbed when bound to either the short or the long Tat peptide. The CD spectra of the complexes indicate an extended structure in the arginine-rich region of Tat from amino acid residue 47 through residue 58 and a short alpha-helix within the adjacent 59-72 region. Models of TAR and its peptide complexes are constructed to integrate these spectroscopic results with current biochemical data. The model suggests that (i) the arginine-rich 49-58 region is primarily responsible for electrostatic interactions with the phosphates of the RNA, (ii) the arginine side chains can additionally interact with substituent groups of the nucleotide bases to confer base recognition in the complex, (iii) the recognition of uracil-23 in TAR is facilitated by the peptide backbone, and (iv) the glutamine-rich face of an alpha-helix within the 59-72 region pairs to bases UGG at nucleotide positions 31-33 in the TAR loop and thus provides an additional motif in the Tat trans activating protein to recognize TAR RNA. PMID- 1409692 TI - Trisomy 7 and trisomy 10 characterize subpopulations of tumor-infiltrating lymphocytes in kidney tumors and in the surrounding kidney tissue. AB - We performed conventional cytogenetic analysis and fluorescence in situ hybridization in short-term cultures of normal and neoplastic kidney tissues. Cell populations carrying an extra chromosome 7 or an extra chromosome 10 as the only chromosome change could be identified in kidney tumors, mostly renal cell carcinomas, and in the surrounding kidney tissue, but not in nonneoplastic kidneys. To identify the type of cells displaying these aneuploidies, we performed in situ hybridization (ISH) with probes specific for the centromeric region of chromosomes 7 and 10 on frozen kidney tissue sections. Trisomy 7 and trisomy 10 were restricted to infiltrating inflammatory cells in the tumor as well as in the surrounding tissue. Trisomy 7 and trisomy 10 were also found in subpopulations of peripheral blood T cells of cancer patients and of normal individuals, as well as in the thymus of five normal fetuses (21-29 weeks), but not in noninvaded reactive lymph node sections of patients without malignancy. When lymphocytes were enriched from kidney tumors and surrounding tissue by either Ficoll/Hypaque density gradient or immunomagnetic selection with anti-CD3, anti-CD4, or anti-CD8 monoclonal antibodies, it was confirmed that they contained a high percentage of trisomy 7 and trisomy 10 cells. Further proof for T lymphocyte origin of the trisomy 7 and trisomy 10 cells was obtained by simultaneous staining of lymphocytes isolated from tumor tissue with anti-CD3, anti-CD4, and anti-CD8 monoclonal antibodies and ISH. We conclude that trisomy 7 and trisomy 10, found in renal carcinomas and surrounding kidney tissue, characterize subpopulations of tumor-infiltrating lymphocytes. The biologic significance of this phenomenon is unknown and requires further investigation. PMID- 1409691 TI - Autoantibodies against a serine tRNA-protein complex implicated in cotranslational selenocysteine insertion. AB - We describe an autoantibody specificity present in a subgroup of patients with a severe form of autoimmune chronic active hepatitis. These antibodies precipitate a 90-nucleotide RNA from human whole cell extracts and recognize a 48-kDa polypeptide in immunoblotting assays. The RNA is a UGA suppressor serine tRNA that carries selenocysteine (tRNA[Ser]Sec)), as shown by sequence analysis. The protein does not appear to be seryl-tRNA synthetase; rather, it is an excellent candidate for a factor involved in cotranslational selenocysteine incorporation in human cells. PMID- 1409693 TI - Recombinant antibody-metallothionein: design and evaluation for radioimmunoimaging. AB - We have produced a chimeric antibody (Ab) in which metallothionein, a well characterized biological chelator of metals, was genetically fused to the F(ab') domain of the S107 Ab heavy chain. Coexpression with the Ab light chain that conveys specificity for the synthetic antigen phosphocholine was achieved in plasmacytoma cells. Metal- and antigen-binding domains of the Ab-metallothionein hybrid function with normal avidity and specificity. Ab-metallothionein can be efficiently loaded with 99mTc and used to specifically bind phosphocholine haptenated cells in vitro or to localize plasma-cell ascites tumors in mice. The approach offers potential advantages for producing radiolabeled Ab for targeted radiotherapy and diagnostic imaging. PMID- 1409694 TI - Metal-binding chimeric antibodies expressed in Escherichia coli. AB - Metallothionein, a well-characterized biological chelator of metals, has been genetically fused to the binding domain of an antibody and expressed in the periplasm of Escherichia coli. Specific delivery of 109Cd to immobilized hapten or to haptenated cells was demonstrated directly in periplasmic extracts. This approach is potentially useful for targeted radiotherapy and diagnostic imaging. We find six to seven atoms of metal per active antigen-combining site. Absence of the Fc portion of the immunoglobulin along with low immunogenicity of metallothionein-metal complexes should reduce immunologic reactions. PMID- 1409695 TI - A broad molecular phylogeny of ciliates: identification of major evolutionary trends and radiations within the phylum. AB - The cellular architecture of ciliates is one of the most complex known within eukaryotes. Detailed systematic schemes have thus been constructed through extensive comparative morphological and ultrastructural analysis of the ciliature and of its internal cytoskeletal derivatives (the infraciliature), as well as of the architecture of the oral apparatus. In recent years, a consensus was reached in which the phylum was divided in eight classes as defined by Lynn and Corliss [Lynn, D. H. & Corliss, J. O. (1991) in Microscopic Anatomy of Invertebrates: Protozoa (Wiley-Liss, New York), Vol. 1, pp. 333-467]. By comparing partial sequences of the large subunit rRNA molecule, and by using both distance-matrix and maximum-parsimony-tree construction methods (checked by boot-strapping), we examine the phylogenetic relationships of 22 species belonging to seven of these eight classes. At low taxonomic levels, the traditional grouping of the species is generally confirmed. At higher taxonomic levels, the branching pattern of these seven classes is resolved in several deeply separated major branches. Surprisingly, the first emerging one contains the heterotrichs and is strongly associated with a karyorelictid but deeply separated from hypotrichs. The litostomes, the oligohymenophorans, and the hypotrichs separate later in a bush like topology hindering the resolution of their order of diversification. These results show a much more ancient origin of heterotrichs than was classically assumed, indicating that asymmetric, abundantly ciliated oral apparatuses do not correspond to "highly evolved" traits as previously thought. They also suggest the occurrence of a major radiative explosion in the evolutionary history of the ciliates, yielding five of the eight classes of the phylum. These classes appear to differ essentially according to the cytoskeletal architecture used to shape and sustain the cellular cortex (a process of essential adaptative and morphogenetic importance in ciliates). PMID- 1409696 TI - Molecular phylogenetic inference from saber-toothed cat fossils of Rancho La Brea. AB - A method for the successful extraction of sequestered cellular DNA from 14,000 year-old fossil bones was developed and applied to asphalt-preserved specimens of the extinct saber-toothed cat, Smilodon fatalis. Two distinct gene segments, the mitochondrial gene for 12S rRNA and nuclear FLA-I (the feline class I major histocompatibility complex gene), from three different individual fossil specimens were cloned and sequenced after PCR amplification. Comparison of fossil derived DNA sequences to homologous regions in 15 living carnivorous species, including 9 species of Felidae and 6 nonfelids, affirmed the phylogenetic placement of Smilodon within the modern radiation of Felidae distinct from the Miocene paleofelid (Nimravidae) saber-toothed "cat" species. These results raise the prospect of obtaining genetically informative DNA from preserved bones of extinct fossil species, particularly among the 2 million specimens excavated from the asphaltic sediments at Rancho La Brea in metropolitan Los Angeles. PMID- 1409697 TI - Genetic analysis of the interaction between bacteriophage T7 DNA polymerase and Escherichia coli thioredoxin. AB - Gene 5 protein of bacteriophage T7 is a nonprocessive DNA polymerase. During infection of Escherichia coli, T7 annexes the host protein thioredoxin for use as a processivity factor for T7 DNA polymerase. We describe here a genetic method to investigate the interaction between T7 gene 5 protein and E. coli thioredoxin. The strategy is to use thioredoxin mutants that are unable to support the growth of wild-type T7 phage to select for T7 revertant phage that suppress the defect in thioredoxin. A thioredoxin mutation that replaces glycine at position 74 with aspartic acid fails to support the growth of wild-type T7. This mutation is suppressed by six different mutations within T7 gene 5, each of which results in a single amino acid substitution within gene 5 protein. Three of the suppressor mutations are located within the putative polymerization domain of gene 5 protein, and three are located within the putative 3'-to-5' exonucleolytic domain. Each suppressor mutation alone is necessary and sufficient to confer the revertant phenotype. PMID- 1409698 TI - Establishment of a highly sensitive and specific exon-trapping system. AB - We have established a highly sensitive and specific exon-trapping system (SETS) with a specific plasmid vector in which an exon in a given DNA segment is identified by its ability to remain as a mature mRNA after splicing. The SETS provides us with the isolation of possible exons rapidly and easily from DNA fragments in chromosomal regions of more than 300 kilobase pairs. Genomic DNA fragments were partially digested and subsequently cloned into plasmid pMHC2, an exon-trapping vector we have constructed. These constructs were transfected into COS-7 cells, and consequent RNA transcripts were spliced in the cells. The resulting mature mRNA was harvested and amplified by using reverse transcription PCR. Possible exons can be recognized by the sizes of PCR products and cloned into a plasmid vector. The SETS provides a direct means of cloning exons from genomic DNA of more than 300 kilobase pairs within a short period of time. Using this system, we have screened 300-kilobase-pair genomic DNA segments derived from human chromosome 11q13. Human chromosome 11q13 may contain genes responsible for human cancers, because DNA amplification is observed in several malignant tumors. We have successfully identified exon 2 of the HST1 gene and additional transcribed sequences. PMID- 1409699 TI - Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. AB - There is considerable evidence implicating tumor necrosis factor alpha (TNF alpha) in the pathogenesis of rheumatoid arthritis. This evidence is based not only on the universal presence of TNF-alpha in arthritic joints accompanied by the upregulation of TNF-alpha receptors but also on the effects of neutralizing TNF-alpha in joint cell cultures. Thus, neutralization of TNF-alpha in vitro results in inhibition of the production of interleukin 1, which like TNF-alpha, is believed to contribute to joint inflammation and erosion. To determine the validity of this concept in vivo, the effect of administering TNF-neutralizing antibodies to mice with collagen-induced arthritis has been studied. This disease model was chosen because of its many immunological and pathological similarities to human rheumatoid arthritis. TN3-19.12, a hamster IgG1 monoclonal antibody to murine TNF-alpha/beta, was injected i.p. into mice either before the onset of arthritis or after the establishment of clinical disease. Anti-TNF administered prior to disease onset significantly reduced paw swelling and histological severity of arthritis without reducing the incidence of arthritis or the level of circulating anti-type II collagen IgG. More relevant to human disease was the capacity of the antibody to reduce the clinical score, paw swelling, and the histological severity of disease even when injected after the onset of clinical arthritis. These results have implications for possible modes of therapy of human arthritis. PMID- 1409701 TI - The path of carbon in photosynthesis: improved crop yields with methanol. AB - Foliar sprays of aqueous 10-50% methanol increased growth and development of C3 crop plants in arid environments. The effects of low levels (< 1 ml per plant) of methanol were observed for weeks after the brief time necessary for its rapid metabolism. Within several hours, foliar treatment with methanol resulted in increased turgidity. Plants treated with nutrient-supplemented methanol showed up to 100% increases in yields when maintained under direct sunlight in desert agriculture. In the shade and when winter crops were treated with methanol, plants showed no improvement of growth. When repeatedly treated with nutrient supplemented methanol, shaded plants showed symptoms of toxicity. Repeated methanol treatments with glycine caused increased turgidity and stimulated plant growth without injury under indirect sunlight, but indoors with artificial illumination, foliar damage developed after 48 hr. Addition of glycerophosphate to glycine/methanol solutions allowed treatment of artificially illuminated plants indoors without injury. Plants with C4 metabolism showed no increase in productivity by methanol treatment. Plants given many applications of aqueous methanol showed symptoms of nutrient deficiency. Supplementation with a source of nitrogen sustained growth, eliminating symptoms of deficiency. Adjustment of carbon/nitrogen ratios was undertaken in the field by decreasing the source of nitrogen in the final application, resulting in early maturation; concomitantly, irrigation requirements were reduced. PMID- 1409700 TI - Purification and characterization of 1-aminocyclopropane-1-carboxylate oxidase from apple fruit. AB - 1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyzes the oxidation of ACC to ethylene. Following conventional column fractionation, the enzyme was purified 180-fold to near homogeneity with a specific activity of 20 nmol/(mg.min). This purified enzyme preparation migrated as a single protein band with an apparent molecular mass of 35 kDa on SDS/PAGE and 39 kDa on gel filtration. As in vivo, the purified enzyme required CO2 for activity. Removal of CO2 from the reaction mixture completely abolished the enzyme activity, while 0.5% atmospheric CO2 (0.15 mM in the medium) gave half-maximal activity. The purified enzyme displayed an absolute requirement for Fe2+ and ascorbate. The stoichiometry of the enzymatic reaction was determined: ACC + ascorbate + O2-->C2H4 + HCN + CO2 + dehydroascorbate + 2 H2O. A polyclonal antibody was raised against a synthetic tridecapeptide (PDLEEEYRKTMKE) whose sequence was deduced from the apple pAE12 cDNA [Dong, J. G., Olson, D., Silverstone, A. & Yang, S. F. (1992) Plant Physiol. 98, 1530-1531], which is homologous to tomato cDNAs encoding ACC oxidase. On a Western blot, this antibody specifically recognized the purified ACC oxidase protein. The amino acid composition of the purified enzyme agreed well with that deduced from the pAE12 sequence. When the protein was cleaved with CNBr and one of the peptide fragments was isolated and sequenced for 20 cycles, its sequence (KEFAVELEKLAEKLLDLLCE) precisely matched that predicted from pAE12 (residues 115 134). When preclimacteric apple fruit was treated with ethylene, a parallel increase in in vivo and in vitro ACC oxidase activities was observed, and this increase was accompanied by a concomitant increase in the level of pAE12 transcript. These observations support the conclusion that the isolated ACC oxidase protein is encoded by pAE12. PMID- 1409702 TI - Second-site revertants of an arginine-210 to lysine mutation in the a subunit of the F0F1-ATPase from Escherichia coli: implications for structure. AB - Arg-210 of the a subunit of the Escherichia coli F0F1-ATPase has been proposed previously as a component of the proton pore. A mutant in which lysine was substituted for Arg-210 was generated and was found to be unable to translocate protons. A plasmid carrying this mutation, along with wild-type genes encoding the c and b subunits, was unusual in that it failed to complement a chromosomal c subunit mutation on succinate minimal medium. Three revertants on succinate minimal medium contained plasmids that showed complementation with chromosomal c subunit but not with a-subunit mutations. One of these had a deletion in the a subunit. The other two were point mutations, resulting in the substitution of aspartic acid by Gly-53 and of arginine for Leu-211. The Gly-53 to aspartic acid change implied that Gly-53 and Arg-210 are normally in close proximity. To test this idea further, a series of mutants in which aspartic acid was placed in helix I at positions ranging from 42 to 57 was generated. Full complementation was regained only when the aspartic acid residue was present on the same side of a putative helix as Gly-53 over a span of three turns of the alpha-helix. These results and others suggest modifications of a previously proposed model for the transmembrane helices of the F0 portion of the F0F1-ATPase. The implications of these modifications for the mechanism of proton translocation are discussed. PMID- 1409704 TI - Displacement of BrdUrd-induced YY1 by serum response factor activates skeletal alpha-actin transcription in embryonic myoblasts. AB - Muscle-restricted transcription of the skeletal alpha-actin gene is controlled in part by a positive regulator, serum response factor (SRF), and a negative regulator, F-ACT1, which bind competitively to the most proximal serum response element (SRE1). We show here that F-ACT1 is identical to a transcription factor recently cloned and described as YY1, NF-E1, delta, or UCRBP. We found that although the DNA-binding activity of SRF accumulates during myogenesis, that of YY1 diminishes simultaneously. Myoblasts rendered incapable of differentiation by BrdUrd treatment exhibited the highest level of YY1 and the lowest level of SRF activities. Transfected SRF could directly transactivate the skeletal alpha-actin promoter by overcoming the inhibitory effect of BrdUrd-induced YY1. The transactivation depends on intact SRE DNA elements and requires the DNA binding/dimerization domain of SRF as well as its C-terminal half rich in serines and threonines. Since the functions of YY1 and SRF appear to be developmentally regulated, the convergence of their binding sites upon the SRE constitutes an integrated mechanism whereby temporal and spatial muscle gene expression may be accomplished. PMID- 1409703 TI - Two members of a widely expressed subfamily of hormone-stimulated adenylyl cyclases. AB - cDNA encoding a hormone- and guanine nucleotide-stimulated adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] (type 6) from rat liver and kidney has been cloned and expressed. This enzyme is stimulated by forskolin, guanosine 5'-[gamma-thio]triphosphate, and isoproterenol plus GTP but is not stimulated by beta gamma subunits of guanine nucleotide-binding proteins. A second form (type 5), which is 75% similar to type 6, has also been cloned. Both types 5 and 6 cDNAs have multiple messages. PCR-based detection of the mRNA for the type 5 and 6 enzymes indicates that both are widely distributed. Homology analyses indicate at least four distinct subfamilies of guanine nucleotide stimulatory protein regulated adenylyl cyclases. Types 5 and 6 enzymes define one distinct subfamily of mammalian adenylyl cyclases. Diversity of one guanine nucleotide-binding protein-regulated effector may allow different modes of regulation of cell surface signal transmission. PMID- 1409705 TI - Isolation and sequence of a cDNA encoding the precursor of a bombesinlike peptide from brain and early embryos of Xenopus laevis. AB - A cDNA encoding the precursor of a bombesinlike peptide was isolated from brain of Xenopus laevis. The predicted end product resembles neuromedin B, which was originally isolated from mammalian spinal cord. The mRNA for this precursor was also present in gastrointestinal tract and in ovaries. Moreover, it could be detected in early embryos (stage 2 and stage 10) of X. laevis. These findings suggest novel roles for peptides of the bombesin family in oocyte maturation and early amphibian development. PMID- 1409706 TI - Ligation-anchored PCR: a simple amplification technique with single-sided specificity. AB - A simple, efficient, and sensitive technique has been developed for amplification of cDNAs encoding molecules with 5' regions of unknown sequence. In this ligation anchored PCR, T4 RNA ligase is used to covalently link an "anchor" oligonucleotide to first-strand cDNAs. These anchored cDNAs are then amplified by using one PCR primer specific for the anchor and another specific for a sequence within the molecule of interest. The anchor oligonucleotide has been especially designed to facilitate subsequent analysis and cloning of the resultant PCR products. This three-stage procedure does not require purification of product between steps and avoids many of the technical difficulties associated with established anchored PCR protocols. The efficacy of ligation-anchored PCR was demonstrated by amplification of a specific IgG1 cDNA; total RNA equivalent to as few as 100 cells yielded the expected PCR product. PMID- 1409707 TI - Growth hormone induces multiplication of the slowly cycling germinal cells of the rat tibial growth plate. AB - To study the effect of locally infused growth hormone (GH) or insulin-like growth factor I(IGF-I) on slowly cycling cells in the germinal cell layer of the tibial growth plate, osmotic minipumps delivering 14.3 microCi of [3H]thymidine per day were implanted s.c. into hypophysectomized rats, and GH (1 microgram) or IGF-I (10 micrograms) was injected daily through a cannula implanted in the proximal tibia. The opposite leg served as a control. After 12 days of treatment, the osmotic minipumps were removed, and three rats in each group were given GH (20 micrograms/day, s.c.) for an additional 14 days to chase the labeled cells out of the proliferative layers. Labeled cells remained in the germinal layer, in the perichondrial ring, and on the surface of the articular cartilage close to the epiphyseal plate. GH administered together with labeled thymidine significantly increased the number of labeled cells in the germinal cell layer compared to that in the control leg (ratio = 1.95 +/- 0.13), whereas IGF-I showed no stimulatory effect (ratio = 0.96 +/- 0.04). Therefore GH but not IGF-I stimulates the multiplication of the slowly cycling (label-retaining) cells in the germinal layer of the epiphyseal plate. IGF-I acts only on the proliferation of the resulting chondrocytes. PMID- 1409709 TI - Glutamic acid decarboxylase autoantibodies in preclinical insulin-dependent diabetes. AB - Insulin-dependent diabetes mellitus (IDDM) is associated with serum antibodies that precipitate a 64-kDa pancreatic islet cell protein reported to be glutamic acid decarboxylase (GAD; glutamate decarboxylase, EC 4.1.1.15). Previously, antibodies to GAD were found in the rare neurological disorder stiff man syndrome. To demonstrate directly antibodies to GAD, enzymatically active GAD was first purified from fresh human cerebellum. Brain GAD activity was precipitated by noninhibitory antibodies in the sera of 16/26 (62%) subjects defined as having preclinical IDDM (islet cell antibody-positive first-degree relatives of a person with IDDM), 3/13 (23%) with recent-onset IDDM, and 3/3 with the stiff man syndrome. In addition, sera of 5/26 (19%) preclinical and 2/13 (15%) recent-onset IDDM subjects contained antibodies that precipitated GAD but inhibited its activity. Thus, overall, 21/26 (81%) preclinical and 5/13 (38%) recent-onset IDDM subjects had antibodies that precipitated GAD activity. Antibodies to GAD were not detected in sera from subjects with other autoimmune diseases (n = 29) or healthy controls (n = 14). GAD affinity-purified to homogeneity (specific activity, 58 units/mg) was specifically immunoprecipitated as a single 60-kDa species by the IDDM sera. In an ELISA incorporating whole mouse brain GAD captured by the GAD-6 monoclonal antibody the frequencies of GAD antibodies for all subject groups were indistinguishable from those found by precipitation of human brain enzymatic activity. We conclude that (i) GAD is an (auto)antigen in a majority of subjects operationally defined as having preclinical IDDM, (ii) pancreatic islet and brain GAD are likely to be cross-reactive, and (iii) the majority of GAD antibodies are directed away from the catalytic site of the brain enzyme. The lower frequency of GAD antibodies in recent-onset IDDM subjects indicates either that immunoreactivity is lost with near-total beta-cell destruction or that GAD antibodies denote a low risk of progression to clinical disease. PMID- 1409708 TI - Roles of selection and recombination in the evolution of type I restriction modification systems in enterobacteria. AB - Restriction-modification systems can protect bacteria against viral infection. Sequences of the hsdM gene, encoding one of the three subunits of type I restriction-modification systems, have been determined for four strains of enterobacteria. Comparison with the known sequences of EcoK and EcoR124 indicates that all are homologous, though they fall into three families (exemplified by EcoK, EcoA, and EcoR124), the first two of which are apparently allelic. The extent of amino acid sequence identity between EcoK and EcoA is so low that the genes encoding them might be better termed pseudoalleles; this almost certainly reflects genetic exchange among highly divergent species. Within the EcoK family the ratio of intra- to interspecific divergence is very high. The extent of divergence between the genes from Escherichia coli K-12 and Salmonella typhimurium LT2 is similar to that for other genes with the same level of codon usage bias. In contrast, intraspecific divergence (between E. coli strains B and K-12) is extremely high and may reflect the action of frequency-dependent selection mediated by bacteriophages. There is also evidence of lateral transfer of a short sequence between E. coli and S. typhimurium. PMID- 1409710 TI - von Willebrand disease type B: a missense mutation selectively abolishes ristocetin-induced von Willebrand factor binding to platelet glycoprotein Ib. AB - von Willebrand factor (vWF) is a multimeric glycoprotein that mediates the adhesion of platelets to the subendothelium by binding to platelet glycoprotein Ib. For human vWF, this interaction can be induced in vitro by the antibiotic ristocetin or the snake venom protein botrocetin. A missense mutation, Gly-561- >Ser, was identified within the proposed glycoprotein Ib binding domain of vWF in the proband with von Willebrand disease type B, a unique variant characterized by no ristocetin-induced, but normal botrocetin-induced, binding to glycoprotein Ib. The corresponding mutant recombinant protein, rvWF(G561S), formed normal multimers and exhibited the same functional defect as the patient's plasma vWF, confirming that this mutation causes von Willebrand disease type B. These data show that botrocetin and ristocetin cofactor activities of vWF can be dissociated by a point mutation and confirm that these mediators promote vWF binding to platelets by different mechanisms. The normal botrocetin-induced binding and the defective ristocetin-induced binding of rvWF(G561S) suggest that the primary defect in von Willebrand disease type B may be a failure of normal allosteric regulation of the glycoprotein Ib binding function of vWF. PMID- 1409712 TI - Growing tips of type I collagen fibrils formed in vitro are near-paraboloidal in shape, implying a reciprocal relationship between accretion and diameter. AB - Collagen fibrils generated in vitro at 37 degrees C by enzymic removal of C terminal propeptides from type I pC-collagen (an intermediate in the normal processing of type I procollagen to collagen containing the C-terminal propeptides but not the N-terminal propeptides) display shape polarity, with one tip fine tapered and the other coarse tapered. Mass measurements by scanning transmission electron microscopy show that the mass per unit length along both kinds of tip increases roughly linearly over distances of approximately 100 D periods from the fibril end [D (axial periodicity) = 67 nm]. The fine tips of fibrils of widely differing lengths exhibit near-identical mass distributions, the mass in all cases increasing at the rate of approximately 17 molecules per D period, irrespective of fibril length. Coarse tips display less regular behavior. These results show that (i) the shape of a fine tip is not conical but resembles more closely a paraboloid of revolution, and (ii) for this shape to be maintained throughout growth, accretion (rate of mass uptake per unit area) cannot everywhere be the same on the surface of the tip but must decrease as the diameter increases. To a first approximation, accretion alpha (diameter)-1. PMID- 1409711 TI - Membrane and synaptic properties of developing lateral geniculate nucleus neurons during retinogeniculate axon segregation. AB - During the first postnatal month in the ferret (Mustela putorius furo), the projections from the retina to the lateral geniculate nucleus (LGN) become segregated into eye-specific layers and ON and OFF sublayers, a process that is thought to depend in part on neuronal activity. Remarkably, virtually nothing is known about the physiological features of LGN neurons during this period. We have recorded intracellularly from 46 A-layer neurons in slices of the ferret LGN between the ages of postnatal days 7 and 33. The passive membrane properties and current-voltage relationships of the developing neurons were similar in many, though not all, respects to those of adult LGN neurons. Action potentials in younger animals were smaller in amplitude and longer in duration than in older animals, but cells at all ages were capable of producing spike trains whose latency and spike number varied with stimulus intensity. In addition, cells at all ages responded with low-threshold potentials upon release from hyperpolarization. Slightly more than half of the LGN neurons responded to optic tract stimulation with excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic potentials (IPSPs), or EPSP-IPSP pairs, beginning with the youngest ages. Thus, as early as the second postnatal week, and much before the onset of pattern vision, LGN neurons have many of the membrane and synaptic properties of adult thalamic neurons. These data are consistent with LGN cells playing a significant role in activity-dependent reshaping of the retinogeniculate pathway. PMID- 1409713 TI - Helical model of nucleation and propagation to account for the growth of type I collagen fibrils from symmetrical pointed tips: a special example of self assembly of rod-like monomers. AB - A model was developed to account for the recent observations indicating that type I collagen fibrils assembled in vivo grow from symmetrical pointed tips. The essential features of the model are (i) a distinctive structural nucleus forms at each end of a growing fibril and growth of the fibril then proceeds by propagation of the two structural nuclei, (ii) the two structural nuclei have similar spiral or helical conformations, and (iii) assembly of each structural nucleus requires two kinds of specific binding steps defined as 3.4 D-period and 0.4 D-period overlaps, but propagation of the nucleus requires only the 3.4 D period binding step. PMID- 1409714 TI - Genetically engineered rice resistant to rice stripe virus, an insect-transmitted virus. AB - The coat protein (CP) gene of rice stripe virus was introduced into two japonica varieties of rice by electroporation of protoplasts. The resultant transgenic plants expressed the CP at high levels (up to 0.5% of total soluble protein) and exhibited a significant level of resistance to virus infection. Plants derived from selfed progeny of the primary transformants also expressed the CP and showed viral resistance, indicating stable transmission of the CP gene and the trait of resistance to the next generation. Moreover, the virally encoded strip disease specific protein was not detected in transgenic plants expressing CP 8 weeks after inoculation, indicating protection before viral multiplication. These studies demonstrated that CP-mediated resistance to virus infection can be extended to cereals and to the viruses transmitted by an insect vector (planthopper). PMID- 1409715 TI - Inhibition of human immunodeficiency virus type 1 replication in human T cells by retroviral-mediated gene transfer of a dominant-negative Rev trans-activator. AB - Human immunodeficiency virus type 1 (HIV-1) is the causative agent of the acquired immunodeficiency syndrome (AIDS). Currently, no satisfactory treatment for this viral disease is available. Somatic gene therapy has been proposed as an alternative to conventional therapies. Several antiviral gene therapy approaches including ribozymes, antisense inhibition, and RNA-decoy strategies, as well as dominant-negative mutants of HIV-1 proteins (Gag, Tat, and Rev) have been suggested. To prove the concept of trans-dominant inhibition of HIV-1 replication, we transduced CEM cells with a retroviral vector encoding a dominant negative rev gene. Amplification of integrase-specific proviral sequences from high molecular weight DNA indicated successful HIV-1 human T-lymphotropic virus type IIIB (HTLV-IIIB) infection of all cells. In contrast to CEM cells and CEM cells expressing the rev wild-type (wt) gene, infection of two CEM-RevM10 clones with HIV-1 did not result in the release of significant levels of p24 Gag antigen as measured by antigen capture assay, indicating a block in HIV-1 replication due to the presence of the trans-dominant Rev protein. Furthermore, the parental CEM cells as well as CEM cells expressing the Rev wt protein were effectively killed in the course of the HIV-1 infection, whereas all CEM cells expressing the RevM10 protein were unaffected in their growth rate. PMID- 1409716 TI - A 105-kDa protein is required for yeast mitochondrial RNase P activity. AB - RNase P from the mitochondria of Saccharomyces cerevisiae was purified to near homogeneity > 1800-fold with a yield of 1.6% from mitochondrial extracts. The most abundant protein in the purified fractions is, at 105 kDa, considerably larger than the 14-kDa bacterial RNase P protein subunits. Oligonucleotides designed from the amino-terminal sequence of the 105-kDa protein were used to identify and isolate the 105-kDa protein-encoding gene. Strains carrying a disruption of the gene for the 105-kDa protein are viable but respiratory deficient and accumulate mitochondrial tRNA precursors with 5' extensions. As this is the second gene known to be necessary for yeast mitochondrial RNase P activity, we have named it RPM2 (for RNase P mitochondrial). PMID- 1409717 TI - A protein methyltransferase specific for altered aspartyl residues is important in Escherichia coli stationary-phase survival and heat-shock resistance. AB - Proteins are subject to spontaneous degradation reactions including the deamidation, isomerization, and racemization of asparaginyl and aspartyl residues. A major product of these reactions, the L-isoaspartyl residue, is recognized with high affinity by the protein-L-isoaspartate(D-aspartate) O methyltransferase (EC 2.1.1.77). This enzyme catalyzes the methyl esterification of the L-isoaspartyl residue in a reaction that can initiate its conversion to the normal aspartyl configuration. To directly study the physiological role of this methyltransferase, especially with respect to the potential repair of isomerized aspartyl residues in aging proteins, we examined the ability of the bacterium Escherichia coli to survive in the absence of its activity. We utilized gene disruption techniques to replace the chromosomal copy of the pcm gene that encodes the methyltransferase with a kanamycin-resistance cassette to produce mutants that have no detectable L-isoaspartyl methyltransferase activity. Although no changes in exponential-phase growth were observed, pcm- mutants did not survive well upon extended culture into stationary phase or upon heat challenge at 55 degrees C. These results provide genetic evidence for a role of the L-isoaspartyl methyltransferase in the metabolism of altered proteins that can accumulate in aging cells and limit their viability. PMID- 1409718 TI - Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts. AB - The human CCND1 cyclin D1/PRAD1 gene was previously identified by a genetic screen for G1 cyclin function in Saccharomyces cerevisiae and also was identified as the putative BCL1 oncogene. However, its role in human cell proliferation is not known. To determine if expression of human D-type cyclin genes correlates with the state of cell growth, we examined the level of mRNAs for CCND1 and a related gene, CCND3, in normal human diploid fibroblasts (HDF). The levels of both mRNAs decrease upon serum depletion or at high cell densities. Following stimulation of quiescent fibroblasts with serum, the mRNA levels increase gradually to a peak at about 12 hr, prior to the onset of S phase. Induction of cyclin gene expression by serum is reduced concomitantly with the decline in FOS induction in aging HDFs, suggesting a possible relationship to the decrease in the proliferative response to mitogens during cellular senescence. Cycloheximide partially blocks the induction of CCND1 and CCND3 gene expression by serum, suggesting that both de novo protein synthesis-dependent and -independent pathways contribute to induction. Treatment of HDFs with defined growth factors suggests a correlation between CCND mRNA induction and DNA synthesis. However, induction of these genes is not sufficient for the transition from quiescence through G1 into S phase. PMID- 1409719 TI - Brain-derived neurotrophic factor and neurotrophin 3 mRNAs in the peripheral target fields of developing inner ear ganglia. AB - In situ hybridization was used to study the site and timing of the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 5 (NT-5) mRNAs in the developing inner ear of the rat. In the sensory epithelia, the levels of NGF and NT-5 mRNAs were below the detection limit. NT-3 and BDNF mRNAs were expressed in the otic vesicle in overlapping but also in distinct regions. Later in development, NT-3 transcripts were localized to the differentiating sensory and supporting cells of the auditory organ and vestibular maculae. In these sensory epithelia, the intensity of NT-3 mRNA expression decreased in parallel with maturation. The expression of BDNF mRNA was restricted to the sensory cells of both the auditory and vestibular organs, including ampullary cristae. In bioassays, BDNF and NT-3, but not NGF, at physiological concentrations induced neurite outgrowth from the statoacoustic ganglion explants. These results demonstrate that NT-3 and BDNF, rather than NGF and NT-5, are the primary neurotrophins present in the target fields of the cochlear and vestibular neurons. Expression of NT-3 and BDNF mRNAs in the otic vesicle before and during the ingrowth of neurites from the statoacoustic ganglion suggests that NT-3 or BDNF or both may serve as chemoattractants for the early nerve fibers. The results also suggest that these neurotrophins have a role in later development of the cochlear and vestibular neurons. PMID- 1409720 TI - Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. AB - Hypophosphatasia is a heritable form of rickets/osteomalacia with extremely variable clinical expression. Severe forms are inherited in an autosomal recessive fashion; the mode of transmission of mild forms is uncertain. The biochemical hallmark of hypophosphatasia is deficient activity of the tissue nonspecific isozyme of alkaline phosphatase (TNSALP). Previously, we demonstrated in one inbred infant that an identical missense mutation in both alleles of the gene encoding TNSALP caused lethal disease. We have now examined TNSALP cDNAs from four unrelated patients with the severe perinatal or infantile forms of hypophosphatasia. Each of the eight TNSALP alleles from these four individuals contains a different point mutation that causes an amino acid substitution. These base changes were not detected in at least 63 normal individuals and, thus, appear to be causes of hypophosphatasia in the four patients. (Two additional base substitutions, found in one allele from each of the four patients, are linked polymorphisms.) Twenty-three unrelated patients (of 50 screened), who reflect the entire clinical spectrum of hypophosphatasia, possess one of our of the above eight mutations. In two of these additional patients, mild forms of the disease are also inherited in an autosomal recessive fashion. Our findings indicate that hypophosphatasia can be caused by a number of different missense mutations and that the specific interactions of different TNSALP mutant alleles are probably important for determining clinical expression. Severe forms, perinatal and infantile disease, are largely the result of compound heterozygosity for different hypophosphatasia alleles. At least some cases of childhood and adult hypophosphatasia are inherited as autosomal recessive traits. PMID- 1409721 TI - Targeting of the T-cell receptor zeta-chain gene in embryonic stem cells: strategies for generating multiple mutations in a single gene. AB - The T-cell receptor zeta chain is a member of a family of related proteins that play a critical role in coupling cell-surface receptors to intracellular signaling pathways. To study the role of zeta chain in T-cell ontogeny, we generated targeted mutations of the zeta-chain gene in murine embryonic stem cells. The mutant alleles are predicted to result either in a null phenotype or in the synthesis of a truncated protein capable of supporting T-cell-receptor surface expression but deficient in transmembrane signaling. Both of these targeting events were recovered in a single electroporation experiment with either coelectroporation or a combination deletion/truncation construct. Our results suggest that similar approaches could be used to generate multiple single mutations, modifications of more than one site within a gene, or subtle alterations that rely upon coconversion with the selectable marker gene. PMID- 1409722 TI - A phorbol ester response element within the human T-cell receptor beta-chain enhancer. AB - The activity of the T-cell receptor beta-chain gene enhancer is increased by activators of the protein kinase C pathway during T-cell activation. Analysis of mutant enhancer constructs identified two elements, beta E2 and beta E3, conferring phorbol ester inducibility. Multimerized beta E2 acted in isolation as a phorbol ester-responsive element. Both beta E2 and beta E3, which contain a consensus Ets-binding site, were shown to bind directly to the product of the c ets-1 protooncogene. Both regions also bound a second factor, core-binding factor. Mutation of the beta E2 Ets site abolished the inducibility of the beta E2 multimer. beta E2 and beta E3 Ets site mutations also profoundly affected activity and inducibility of the enhancer. In contrast, enhancer activity but not its inducibility was affected by mutation of the beta E2 core-binding factor site. Cotransfection studies showed that Ets-1 specifically repressed activity of the multimerized beta E2 element and the complete T-cell receptor beta-chain enhancer. These data show that the T-cell receptor beta-chain enhancer responds to protein kinase C-mediated activation signals via a functional domain, composed of two elements, which contains binding sites for Ets transcription factors and which is negatively regulated by Ets-1. PMID- 1409723 TI - Selective disruption of growth hormone transcription machinery by viral infection. AB - Viruses that establish persistent infections may show selective and unique effects on the host's transcriptional machinery. Lymphocytic choriomeningitis virus (LCMV), a noncytolytic virus, can persistently infect a rat pituitary cell line. Although the infected cells remain free of structural damage, virus markedly interferes with growth hormone (GH) but only minimally interferes with prolactin transcription. The study of GH promoter-chloramphenicol acetyltransferase-transfected cells and GH promoter deletion mutants demonstrates that the viral effect is at the level of GH promoter and is due to interference with GH transactivator factor GHF1 (Pit1). Treatment of LCMV-infected cells with the antiviral agent ribavirin cures the infection and restores normal GH mRNA levels. These results illustrate a molecular mechanism by which a virus infection can disrupt synthesis of a cell's differentiated product without perturbing vital cellular functions. PMID- 1409724 TI - Leishmania infections damage the feeding mechanism of the sandfly vector and implement parasite transmission by bite. AB - Leishmania parasites are transmitted by the bites of infected female sandflies by a mechanism that has not been clarified. Leishmania infections in the vector develop only in the gut, and the parasites' exit is through the food channel in the proboscis. The problem is how during the bite, when blood flows in, parasites are emitted through the same channel in the opposite direction. It is well documented that infected sandflies maintained on sugar diets are potent vectors, whereas transmission fails after constant feeding on blood. Hence to study the mechanism of transmission, we fed these diets to Phlebotomus papatasi infected with L. major. Histological examination demonstrated that only in the sugar-fed flies did the cuticle lining of the cardiac valve detach and other valve tissues degenerate gradually. The injury of the main valve of the food pumps hindered gorging of most flies when force-fed from capillaries, and they regurgitated the gut contents with fluids from the capillaries. We suggest that infections are caused by parasites regurgitated from the stomach that are deposited in the host tissue. We found that secretion of chitinolytic enzymes by cultured L. major parasites is inhibited by blood or hemoglobin, and hence these enzymes are apparently absent from the blood-fed infected flies, where the cardiac valve appears undamaged. We therefore presume that lysis of the chitin in the cuticle lining of the valve leads to exposure and degeneration of the underlying tissues. PMID- 1409725 TI - Progesterone modulates a neuronal nicotinic acetylcholine receptor. AB - The major brain nicotinic acetylcholine receptor is assembled from two subunits termed alpha 4 and n alpha 1. When expressed in Xenopus oocytes, these subunits reconstitute a functional acetylcholine receptor that is inhibited by progesterone levels similar to those found in serum. In this report, we show that the steroid interacts with a site located on the extracellular part of the protein, thus confirming that inhibition by progesterone is not due to a nonspecific perturbation of the membrane bilayer or to the activation of second messengers. Because inhibition by progesterone does not require the presence of agonist, is voltage-independent, and does not alter receptor desensitization, we conclude that the steroid is not an open channel blocker. In addition, we show that progesterone is not a competitive inhibitor but may interact with the acetylcholine binding site and that its effect is independent of the ionic permeability of the receptor. PMID- 1409726 TI - Paradoxical increase in striatal neuropeptide gene expression following ischemic lesions of the cerebral cortex. AB - Ischemic lesions of the cerebral cortex occur frequently in humans as a result of stroke. One major consequence of the death of cortical neurons is the loss of excitatory cortical projections to subcortical regions. Little is known, however, about the transsynaptic effect of such lesions on neurotransmitter expression in subcortical structures. We have examined the effects of ischemic cortical lesions on the peptidergic neurotransmitters enkephalin and tachykinins in the striatum, a brain region massively innervated by glutamatergic cortical inputs. The levels of enkephalin and tachykinin mRNAs increased in the striatum of adult rats after thermocoagulation of pial vessels. The effects were more pronounced in the striatal region most heavily innervated by the lesioned cortex but were also observed in other striatal regions and on the contralateral side. Increased gene expression was accompanied by increased immunoreactivity for the two peptides. Elevated levels of enkephalin mRNA were observed up to 3 months after surgery in the ipsilateral striatum. Whereas results of previous studies of acute cortical ablations suggested that excitatory corticostriatal neurons were necessary to maintain normal peptide levels in striatal efferent neurons, the present data indicate that lesions of the same corticostriatal neurons secondary to local ischemia result in a paradoxical transsynaptic activation of neuropeptide synthesis in subcortical structures. This effect may play a role in the functional consequences of cortical strokes and progressive cortical atrophy in humans and may have critical bearing for their treatment and prognosis. PMID- 1409727 TI - Unsaturation of fatty acids in membrane lipids enhances tolerance of the cyanobacterium Synechocystis PCC6803 to low-temperature photoinhibition. AB - Effect of the unsaturation of fatty acids in the glycerolipids of thylakoid membranes on low-temperature photoinhibition of photosynthesis was studied by mutation and transformation of the cyanobacterium Synechocystis PCC6803. When grown at 34 degrees C, the wild type contained mono-, di-, and triunsaturated lipids; a mutant, designated Fad6, contained mono- and diunsaturated lipids; and a transformant of Fad6, with a disrupted gene for desaturation and designated Fad6/desA::Kmr, contained only monounsaturated lipids. Fad6/desA::Kmr was the most susceptible among these strains to low-temperature photoinhibition of photosynthesis, whereas Fad6 and the wild type were apparently indistinguishable in terms of sensitivity to photoinhibition. This result suggests that the presence of diunsaturated fatty acids is important in protecting against low temperature photoinhibition. The photoinhibition at room temperature, although much less significant than that at low temperature, was also affected by the unsaturation of fatty acids. By contrast, the photosynthetic transport of electrons, measured at various temperatures, was not affected by changes in extent of fatty acid unsaturation. PMID- 1409728 TI - Fetal Leydig cells: cellular origin, morphology, life span, and special functional features. AB - The Leydig cells, responsible for testicular androgen production, have two growth phases during the life-span of mammals. The fetal population appears during fetal life and is responsible for the androgen-induced differentiation of the male genitalia. The fetal Leydig cells disappear after birth, and the other population, the adult Leydig cells, appears during puberty and persists for the whole adult life. The fetal Leydig cells, evidently due to the intrauterine endocrine milieu and their special functional requirements in genital differentiation, differ both morphologically and functionally from the adult population. The purpose of this review is to elucidate the special features of the mammalian fetal Leydig cell population, which presents an intriguing experimental model for studies of function and regulation of steroidogenic cells. PMID- 1409729 TI - Vitamin A homeostasis endangered by environmental pollutants. AB - Normal vitamin A function depends on adequate stores of the vitamin, a finely regulated supply of the vitamin to target tissues, and an ability of cells to generate functionally active forms of the vitamin. Both endogenous and exogenous factors can adversely affect vitamin A homeostasis. Polyhalogenated aromatic hydrocarbons are ubiquitous environmental pollutants and cause severe disturbances in vitamin A metabolism, manifested by an accelerated metabolism and breakdown of vitamin A and its metabolites and a depletion of vitamin A from the body; this sequence of events accounts for the vitamin A deficiency-like symptoms associated with PHAH intoxication. The mechanism(s) responsible for these events most likely includes altered activities of enzymes that are either directly or indirectly involved in critical vitamin A metabolic pathways. Human populations that continue to be exposed to environmental pollutants, may accumulate critical levels of polyhalogenated aromatic hydrocarbons and will be at risk for inadequate vitamin A function as well as for other health impairments that have been difficult to link to any specific causes. Therefore, it is important to seriously evaluate the similarities in physiological disturbances across species that have become apparent in studies with wildlife inhabiting polluted environments similar to ours; the relevance to human health is evident. PMID- 1409730 TI - C-receptor ligand blocks pulmonary clearance of atrial natriuretic peptide in isolated rat lungs. AB - Pulmonary clearance of atrial natriuretic peptide (ANP) was measured by indicator dilution technique in isolated perfused rat lungs with and without ANP clearance receptor (C-receptor) blockade. Approximately 50% of a bolus injection of 125I ANP was removed during a single pass through the lungs compared with the intravascular marker 14C-dextran. Pulmonary clearance of 125I-ANP was suppressed in a dose-dependent fashion by unlabeled ANP. C-receptor blockade suppressed pulmonary clearance of 125I-ANP to the same degree as unlabeled ANP. High performance liquid chromatography analysis of the pulmonary venous effluent from lungs treated with C-receptor ligand demonstrated intact 125I-ANP. We conclude that virtually all of the pulmonary vascular uptake of 125I-ANP during a single pass through isolated lungs is secondary to removal by ANP C-receptors. PMID- 1409731 TI - Induction of pancreatic acinar pathology via inhalation of nicotine. AB - This study was conducted to determine the effects of nicotine inhalation on the onset, progression, and sequential development of pancreatic lesions. Male Sprague-Dawley rats in groups of five were exposed to saline or nicotine aerosol twice daily for 15, 30, 45, and 60 min for 21 days. After sacrifice, blood samples were analyzed for plasma levels of nicotine, glucose, gastrin, and cholecystokinin. Pancreatic tissues were examined for pathological lesions. While there were no significant differences in plasma levels of glucose, gastrin, and cholecystokinin in all groups, there was a steady increase in plasma levels of nicotine with increased exposures to nicotine. Histopathological examination of pancreatic tissue revealed definitive pancreatic injuries that also appeared to be directly correlated with increased duration of nicotine exposure. The pathological changes of the pancreas were confined only to acinar cells of the exocrine pancreas. Two main types of cellular changes were observed: cellular swelling/vacuolation and nuclear condensation/cellular pyknosis. Both of these changes indicated tissue injuries in the pancreas. Transformation of the glandular acini to solid masses of epithelial cells was also observed. The results from our present study strongly suggest that the exocrine pancreas is very sensitive and susceptible to nicotine toxicity. Our data further indicate that early morphological changes in the pancreas induced by nicotine may occur without functional or metabolic alterations; however, such changes could occur at a later stage, when tissue and cellular changes become more extensive. PMID- 1409732 TI - Actions of lipoxins A4 and B4 on signal transduction events in Friend erythroleukemia cells. AB - Earlier studies in our laboratory suggested a role for 15-lipoxygenase products of arachidonic acid, such as 15-hydroperoxyeicosatetraenoic acid and 15 hydroxyeicosatetraenoic acid, in supporting proliferative events in Friend erythroleukemia cells. Because lipoxins are also products of the same lipoxygenase enzyme, we tested their actions on signal transduction events related to DNA synthesis. Lipoxins A4 and B4 (10 nM) significantly enhanced [3H]thymidine incorporation into Friend cells in the absence of fetal bovine serum without affecting cell differentiation or cell number. Lipoxin B4 increased the duration of time that cells spent in the S phase of the cell cycle, and also significantly enhanced protein kinase C activity in nuclei, whereas c-fos expression was unaffected by either of the lipoxins tested. The novel, intracellular actions of lipoxins A and B on Friend erythroleukemia cells documented in this study represent a unique spectrum of effects of lipoxins on signal transduction events as compared with other eicosanoids. PMID- 1409733 TI - Effects of calorie restriction on immunologic functions and development of autoimmune disease in NZB mice. AB - Chronic energy (calorie) intake restriction (CEIR) prolonged life, inhibited autoimmune disease, and influenced immunologic and hematologic parameters in NZB mice. Abnormalities in numbers and proportions of T and B cells populations were corrected. Deficient responses to phytomitogens, mixed lymphocyte reactions, formation of plaque-forming cells to sheep red blood cells in vitro, production of cytotoxic T lymphocytes after in vitro stimulation, and interleukin 2 production were also corrected. CEIR prevented the extreme splenomegaly that normally occurs with age in NZB mice. This influence was associated with reduction of a greatly expanded non-T, non-B lymphoid cell population. Calorie restriction also prevented in NZB mice the rapid decrease in total numbers of colony-forming B cells in bone marrow that is also characteristic of mice of this strain. The influences of CEIR on immune parameters and hematopoiesis were generally less marked in non-autoimmune-prone DBA/2 mice than in autoimmune-prone NZB mice. CEIR has been shown to produce profound influences on several strains of autoimmune-prone mice (NZB x NZW)F1, MRL/lpr, BXSB, and NZB herein). In each of these strains, the pathogenesis and manifestations of autoimmune disease are dissimilar. Therefore, it seems likely that calorie restriction acts on an as yet elusive mechanism that operates to foster development of the diseases associated with aging common to each of these autoimmune strains as well as autoimmune resistant mice and rats. Further investigation of the molecular and cellular bases of the benefits of CEIR seems urgent. PMID- 1409735 TI - Inhibition by cocaine of the baroreflex in the rat. AB - Sprague-Dawley rats were fitted under pentobarbital anesthesia with a catheter in the caudal artery and their carotid arteries were exposed. The pressure signal from the caudal artery was treated on line by a microcomputer for continuous display of blood pressure and heart rate measurements. The animals were administered intraperitoneally either 50 mg/kg of cocaine or an equal volume of saline. Five minutes later, stimulation of the baroreflex was performed by bilateral clamping of the two carotids for a period of 2 min. The same maneuver was repeated at 12, 24, and 31 min. Analysis of variance for repeated measures indicated that before carotid artery clamping, there was no significant difference between blood pressure measurements of the saline- and cocaine-treated groups. A two-factor analysis of variance of the repeated measures of the maximal variation in systolic pressure after each clamping showed a significant difference between control and cocaine-administered groups (P < 0.001), with the former displaying a much greater increment in blood pressure after carotid clamping. Cocaine exerts an inhibitory effect on the baroreflex that may be mediated through the increased angiotension II caused by the alkaloid. PMID- 1409734 TI - Effect on vasopressin release of microinjection of cholinergic agonists into the rat supraoptic nucleus. AB - It is likely that central cholinergic pathways to the paraventricular and supraoptic nuclei participate in the control of vasopressin release. We have shown previously that this is due, in part, to activation of muscarinic, but not nicotinic, receptors in the paraventricular nucleus. There is, however, reason to believe that this cholinergic effect in the supraoptic nucleus may be the result of activation of nicotinic receptors. To test this possibility, we have studied in conscious unrestrained rats the effect of microinjection of muscarinic and nicotinic agonists into the supraoptic nucleus on vasopressin release, mean arterial blood pressure, and heart rate. Under ether anesthesia, a stainless steel guide cannula was placed in the supraoptic nucleus 5-7 days before the experiment, and femoral, arterial, and venous catheters were implanted 1 day before the experiment. Microinjection of nicotine into the supraoptic nucleus at doses of 1 and 10 micrograms resulted in transient increases in the plasma vasopressin concentration that were 7-fold and 11-fold greater, respectively, than control values at 3 min. There were also small transient increases in mean arterial blood pressure, but heart rate was unchanged. The microinjection of 2 and 20 ng of oxotremorine, a muscarinic agonist, into the supraoptic nucleus had no effect on the plasma vasopressin concentration, mean arterial blood pressure, or heart rate. These doses of oxotremorine were previously shown to have potent stimulatory effects on vasopressin release when microinjected into the paraventricular nucleus. These findings suggest that the central cholinergic stimulation of vasopressin release is due, in part, to activation of muscarinic receptors in the paraventricular nucleus and nicotinic receptors in the supraoptic nucleus. PMID- 1409736 TI - The metabolism of human sex hormone-binding globulin in the rhesus monkey. AB - The metabolism of human sex hormone-binding globulin (hSHBG) was studied in eight female rhesus monkeys (Macaca mulatta) after the pulse injection of [125I]-hSHBG. hSHBG was iodinated with 125I using a chloramine T technique, and the [125I] hSHBG was separated from other constituents by molecular sieve chromatography with a Sephadex G-25 column. The [125I]-hSHBG was administered intravenously as a pulse in 2 ml of phosphate buffer, pH 7.4, to each of eight rhesus monkeys. Blood samples (2.0 ml) were obtained at 2, 4, 6, 8, 24, 30, 45, and 54 hr after the injection. The glycoproteins were precipitated with concanavalin A-Sepharose, and the radioactivity was measured. The concentration of radioactivity as fraction of dose/ml of serum was plotted on a semilog scale against time. The disappearance of radioactivity could be expressed best as the sum of two exponentials, with a mean +/- SE t1/2 of 2.5 +/- 0.4 and 33.1 +/- 3.7 hr, respectively. The initial volume of distribution was 461 +/- 78 ml and the metabolic clearance rate was 559 +/- 66 ml/day. The very low clearance rate and prolonged t1/2 are compatible with a relative stability in the circulating mass of SHBG. Rapid changes in concentration of SHBG could be due to changes in serum volume, reversible changes in tissue distribution of SHBG, or the secretion of variable forms of desialylated SHBG. PMID- 1409737 TI - Growth hormone secretion, serum, and cerebral spinal fluid insulin and insulin like growth factor-I concentrations in pigs with streptozotocin-induced diabetes mellitus. AB - Diabetes mellitus was induced using streptozotocin in five gilts between 8 and 12 weeks of age. Gilts were maintained with exogenous insulin (INS) except during experimental periods. Four litter-mate gilts served as controls. At 9 months of age, all gilts were ovariectomized, and 30 days after ovariectomy, Experiment (Exp) 1 was conducted. Jugular vein catheters were inserted and blood samples were collected every 10 min for 8 hr. Experiment 2 was conducted when gilts were 11 months of age. Venous blood and cerebrospinal fluid (CSF) samples were collected in the absence (Phase I) or presence (Phase II) of INS therapy. In Experiment 1, plasma glucose concentrations were greater (P < 0.05) in diabetic (465 +/- 17 mg/100 ml) than in control (82 mg +/- 17 mg/100 ml) gilts, whereas serum INS was lower (P < 0.0001) in diabetic gilts (0.3 +/- 0.02 vs 0.9 +/- 0.05 ng/ml) and insulin-like growth factor-I was similar in diabetic and control gilts (32 +/- 3 vs 43 +/- 4 ng/ml, respectively). Mean serum GH concentration was 2 fold greater (P < 0.02) in diabetics (2.8 +/- 0.4 ng/ml) than in control gilts (1.2 +/- 0.2 ng/ml). Diabetic gilts exhibited a greater (P < 0.05) number of GH pulses than control gilts (3.2 +/- 0.4 vs 1.5 +/- 0.3/8 hr, respectively). In addition, GH pulse magnitude was markedly elevated (P < 0.02) in diabetic (5.8 +/ 0.4 ng/ml) compared with control gilts (3.3 +/- 0.6 ng/ml). Mean basal serum GH concentrations were greater (P < 0.07) in diabetic (2.2 +/- 0.5 ng/ml) compared with control gilts (1.0 +/- .1 ng/ml). In Experiment 2, CSF concentrations of insulin-like growth factor-I, INS, GH, and protein were similar for diabetic and control gilts in both phases. Serum GH levels were similar for diabetics and controls in Phase I, but were greater (P < 0.05) in diabetics than in controls in Phase II. CSF glucose levels were greater in diabetic than in control gilts in both the presence (P < 0.003) and absence (P < 0.0002) of INS therapy, whereas plasma glucose was greater (P < 0.003) in diabetic than in control gilts in the absence of INS, but returned to control concentrations in the presence of INS. However, serum GH levels were unchanged after INS therapy in the diabetic gilts. In conclusion, altered GH secretion in the diabetic gilt may, in part, be due to elevated CSF glucose concentrations, which may alter GH-releasing hormone and/or somatostatin secretion from the hypothalamus. PMID- 1409738 TI - The neurology of Alzheimer disease in Down syndrome. PMID- 1409739 TI - Down syndrome: differentiating mental retardation and dementia with brain imaging techniques. PMID- 1409740 TI - Down syndrome and Alzheimer disease. AB - The brains of individuals with Down's syndrome in their 40's and 50's begin to develop changes that are otherwise seen only in patients with Alzheimer disease. Neurons develop neurofibrillary tangles, flame-shaped alterations composed mainly of condensed cytoskeletal proteins. Another protein, beta/A4 amyloid, is deposited in large amounts in the form of senile plaques and, around blood vessels, amyloid angiopathy. With increasing age, Down syndrome individuals accumulate more and more of these changes. Different parts of the brain are affected to varying degrees by these two alterations. Surprisingly, the pattern of accumulation of neurofibrillary tangles and senile plaques is characteristic, and follows a predictable pattern. We have characterized this pattern in the hippocampal formation in a group of Down individuals, ages 13-71. Certain specific neurons such as those in layer II of entorhinal cortex and the CA1/subiculum field of the hippocampus are exquisitely vulnerable to tangle formation, and are the first neurons to be affected. Perhaps 20-30 years pass as the disease process evolves from mild to severe pathological changes. One hypothesis for why Down individuals would be predisposed to developing Alzheimer pathology is the observation that the gene that encodes the precursor of the amyloid protein is located on chromosome 21. An extra copy of this gene, such as occurs in Down syndrome, may lead to "overproduction" of amyloid, and ultimately to its accumulation as senile plaques. Experiments to test this hypothesis are now underway. PMID- 1409741 TI - Down syndrome as a key to the time sequence of brain changes in Alzheimer disease. PMID- 1409742 TI - Clinicopathologic features of Alzheimer disease in Down syndrome. PMID- 1409744 TI - Cellular aspects of Alzheimer neurofibrillary pathology. PMID- 1409743 TI - Amyloid precursor protein (APP) and beta A4 amyloid in Alzheimer's disease and Down syndrome. PMID- 1409745 TI - Mutations in APP and their role in beta-amyloid deposition. PMID- 1409746 TI - Genetic heterogeneity, Down syndrome, and Alzheimer disease. PMID- 1409747 TI - Neurodegeneration and gene dysregulation: studies utilizing the mouse trisomy 16 model of Down syndrome. PMID- 1409748 TI - Animal models of the neuropathology observed in Alzheimer's disease and Down syndrome. PMID- 1409749 TI - Preliminary characterization of long-term reaggregating cultures of trisomy 16 central nervous system. PMID- 1409750 TI - Alzheimer's disease-type brain abnormalities in animal models. PMID- 1409751 TI - Potential role of S100 beta in Alzheimer's disease: an hypothesis involving mitotic protein kinases. PMID- 1409752 TI - Longitudinal study of neuropsychological function in older adults with Down syndrome. PMID- 1409753 TI - Dementia in Down syndrome: methods of evaluation. PMID- 1409754 TI - Parallels between Down syndrome dementia and Alzheimer's disease. PMID- 1409755 TI - [The chemistry and biological activity the the genus Centaurea]. PMID- 1409756 TI - [The therapeutic utilization of magnesium: medical consequences]. AB - To optimize a pharmaceutical formulation, one has to take into account physicochemical, biopharmaceutical, therapeutical and technological properties of the active principle. These properties are investigated in the PREFORMULATION phase. The authors envisage dosage form (capsule) of magnesium and describe two aspects of the active principle: therapeutic and biopharmaceutic. PMID- 1409757 TI - Synthesis and pharmacological activity of imidazo [2,1-b] thiazole nitriles, amides and p-sulfamidophenylhydrazones. AB - The synthesis of three series of new imidazo [2,1-b] thiazoles (nitriles 1-7, amides 8-14 and p-sulfamidophenylhydrazones 15-24) is reported. Among the compounds tested, only 12 showed a borderline diuretic activity. Compounds 15-24, possible prodrugs of sulfanilamide, were devoid of antibacterial activity. PMID- 1409758 TI - In vitro deterioration of rhein anthraquinone in cecal content of rats. AB - The influence of the intestinal microbial reduction of rhein anthraquinone on the formation of deterioration products was studied. Therefore [14C]rhein and [14C]rhein anthrone were mixed with sterilized or non-sterilized cecal mass of rats and incubated for 20 hours at 37 degrees C. Extractions with a methanol water (50:50) mixture or 4-nitroso-N,N-dimethylaniline (0.1%) in pyridine revealed several radioactive derivatives after TLC and autoradiography, except in the case where the anthraquinone was mixed with sterilized cecal content. Gel permeation on a styrene-divinylbenzene copolymer column of an methanol/water extract of non-sterilized cecal content incubated with [14C]rhein, showed radioactive deterioration products with a molecular weight higher than rhein anthraquinone. The high molecular weight of some deterioration products was confirmed by an ultrafiltration study where the methanol/water extract was centrifuged on a Centricon-3 microconcentrator (nominal cutoff: 3000 MW). Aqueous extracts of non-sterilized cecal content incubated with rhein were extracted with chloroform to remove rhein anthraquinone, rhein anthrone and sennidins before being intracecally injected in rats. No laxative activity was found. Furthermore it was shown that the deterioration products which are probably formed through radical reactions, no longer develop a color with a solution of KOH. Therefore it is concluded that the reduction process of dihydroxy-anthraquinones in the gut microflora followed by an extraction, accounts for the loss of anthranoid equivalents in in vivo circumstances, as several times reported in the past. PMID- 1409760 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1409759 TI - An improved gas chromatographic determination of valproic acid and valpromide in plasma. AB - A newly, improved analytical method for determination of valproic acid (VPA) and valpromide (VPD) in human plasma was developed. The method is based on gas chromatographic determination with flame ionization detection, after chloroform extraction of the drugs from plasma. Caprylic acid was used as an external standard. With the extraction procedure chosen, high recoveries for both VPA and VPD were achieved (98-102%), with correlation coefficient of 0.9998 for VPA and 0.9996 for VPD. Sensitivity of the method was also high (2 ng or 2 mg/L), while the linearity was obtained over the range of 5-150 mg/L, with high correlation for both drugs (0.9997 and 0.9995 for VPA and VPD, respectively). Reproducibility of the method was documented with low values of coefficients of variation, both inter-assay and day-to-day values (1.4-4.4 and 1.7-3.7 for VPA and 2.1-5.0 and 2.6-5.1 for VPD, respectively). The method has been used to follow VPA plasma levels in adult epileptic patients on sodium valproate therapy. PMID- 1409761 TI - Role of thymus-eicosanoids in the immune response. AB - The present review deals with the role(s) of thymus-eicosanoids in the immune response. It reports the production of cyclooxygenase and lipoxygenase metabolites of arachidonic acid by cells of the thymus microenvironment and the role(s) of these eicosanoids in the differentiation and the maturation of immature T-cells. The possibility that these products may be involved in tolerance to self is discussed. Briefly, it is likely that cells from the monocyte-macrophage lineage which constitute a part of the thymus microenvironment could contribute to the education of immature thymocytes by both presenting self-antigens and producing eicosanoids. Tolerance to self might result from PGE2-driven apoptosis and/or LTB4-induced generation of suppressor cells. PMID- 1409762 TI - Prostaglandin metabolism in relation to the bowel habits of women. AB - A relationship between the menstrual cycle, changes of bowel habits and concentrations of plasma prostaglandin (PG)E2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (TX)B2 in 3 groups of 8 women with different bowel habit were determined. The concentrations of PGE2, PGF2 alpha and TXB2 were significantly higher in the group who had bowel habits smoother than usual at menses compared to those who had experienced constipation throughout cycle or at menses. However, no differences between at mid-cycle and at menses were observed in the groups who had experienced constipation. These results suggest that constipation of young women is related to the inherited inability of patients to synthesize and secrete PGs in plasma and possibly in small intestine. PMID- 1409763 TI - GC/MS/MS quantification of 11-dehydrothromboxane B2 in human urine. AB - A fully validated stable isotope dilution method for rapid quantification of 11 dehydrothromboxane B2 by gas chromatography/negative chemical ionization tandem mass spectrometry is reported. The interassay coefficient of variation was 1.3%. The relative recovery of synthetic, underivatized 11-dehydrothromboxane B2 added to urine was 84.6 +/- 2.5% (mean +/- SEM, N = 9). The equation of the regression plot correlating the amounts added and recovered was Y = 0.894X-0.23, with R = 0.9963. The late introduction of the pentafluorobenzyl moiety at C11 afforded distinct advantages in the cleanup stage of the assay and during the GC/MS analysis as well. The pair of daughter fragments at m/z 345 and 349 of the parent fragment ions at m/z 615 and 619 were monitored. Excretion values of 11 dehydrothromboxane B2 in 3 healthy male subjects were 975, 615 and 822 ng/24 h. Excretion was reduced to 751, 387 and 465 ng/24 h, respectively, after administration of a fish oil supplement (15 g/day) for 10 weeks. PMID- 1409764 TI - Effect of sodium and chloride depletion on urinary prostaglandin F2 alpha excretion in potassium loaded rats. AB - Previous studies have shown that the urinary excretion of prostaglandin (PG) F2 alpha is stimulated by potassium (K) loading. Because changes of sodium chloride (NaCl) intake also affect renal PG production, in this study we investigated the interaction between the effect of K and that of concomitant reduction of Na and Cl intake. The urinary excretion of PGF2 alpha and PGE2 was measured in 12 groups of female rats on normal, high or low K intake. Na and Cl intake were adjusted so that rats had normal intake (controls, C), were selectively Cl depleted (CD), selectively Na depleted (ND) or Na and Cl depleted (NCD). In rats with normal K intake, urinary PGF2 alpha was not modified by changes of Na or Cl intake, whereas PGE2 was increased in by Cl depletion (in both NCD or CD groups). Potassium chloride loading increased urinary PGF2 alpha and selective Na depletion (ND group) induced a further increase. On the other hand, PGF2 alpha was not stimulated when K load was associated with Cl depletion. Urine PGF2 alpha was directly correlated with plasma aldosterone and urinary kallikrein. Urinary PGE2 did not change with K-loading. The results suggest that PGF2 alpha participates in the renal adaptation to KCl-loading but not when K is accompanied by non-Cl anions. PMID- 1409765 TI - A drug used in traditional medicine, harpagophytum procumbens: no evidence for NSAID-like effect on whole blood eicosanoid production in human. AB - Devil's Claw (Harpagophytum procumbens), an herbal product being marketed in Canada and in Europe as a home remedy for the relief of arthritic disease, was investigated in healthy humans on eicosanoid production during spontaneously blood clotting. Volunteers took H. procumbens (daily 4 capsules of 500 mg powder containing 3% of total glucoiridoids) for a period of 21 days. The following are the results (mean (SEM)): before H. procumbens intake, prostaglandin (PG)E2 (ng/ml serum): 2.1 (0.4) (n = 25), thromboxane (TX)B2: 147 (27) (n = 25), 6-keto PGF1 alpha: 4.4 (0.7) (n = 13), leukotriene (LT)B4: 3.4 (0.4) (n = 25); after intake: PGE2: 3.2 (0.6), TXB2: 143 (24), 6-keto-PGF1 alpha: 4.2 (0.9), LTB4: 3.8 (0.6). Each subject serving as her own control, no statistically significant differences were observed between before and after H. procumbens intake. These results indicate that Devil's Claw lacks, at least in healthy humans and under the selected conditions, the biochemical effects on arachidonic acid metabolism of antiarthritic drugs of the non-steroidal antiinflammatory type. PMID- 1409766 TI - Prostaglandin E2 and leukotriene C4 levels following different reperfusion periods in rat brain correlated with morphological changes. AB - Prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) are the metabolites of arachidonic acid (AA) that increase in forebrain following global ischemia and reperfusion. These mediators are highly potent vasoconstrictors of cerebral arteries leading to enhanced vascular permeability that induces the formation of vasogenic edema. In this study, after developing an experimental animal model simulating the concept of ischemic penumbra in the rat, the levels of PGE2 and LTC4 produced in the forebrain were measured and the effects of these mediators in short duration and prolonged reperfusion were investigated and then correlated with neuropathological findings. We found statistically significant reduction both in PGE2 and LTC4-like activities after just 10 min ischemia (p less than 0.05, p less than 0.05). PGE2-like activity significantly increased in the 4th and 60th min of reperfusion (p less than 0.05, p less than 0.05). In the 15th min of reperfusion, PGE2 was found to be significantly reduced (p less than 0.005) that may be due to the formation of free oxygen radicals by activation of PG hydroperoxidase reaction that inhibits PGE2 production in the cyclooxygenase pathway. LTs were not significantly increased in any reperfused group. Inhibition of the lipoxygenase pathway of AA metabolism may occur as a result of 15-HPETE (15-hydroperoxyeicosatetraenoic acid) production. Pathologically, edema and degeneration of brain tissue were seen beginning from the 4th min of reperfusion that reached a peak in the 60th min of reperfusion which is in accordance with biochemical changes in the damaged tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409767 TI - The effects of a 5-lipoxygenase inhibitor, AA-861, on PGI2-like substance production in guinea-pig lungs. AB - To determine the effects of AA-861 on PGI2 production in guinea-pig lungs, 3 g of guinea-pig lung was chopped in 4 ml of buffer (control group), in buffer with 4 micrograms/ml indomethacin (indomethacin group) and in buffer with 2.5 x 10(-5)M AA-861 (AA-861 group). The chopped lungs were incubated for 30 min. 250 microliters of incubation medium from each group was assessed before and after 3, 5, 10, 15, 20, 25 and 30 min of incubation. The incubation medium was centrifuged and the supernatant was tested for a PGI2-like substance (PGI2) by platelet aggregation inhibition. PGI2 was produced mainly during the initial 3-5 min of incubation and was decreased thereafter. PGI2 production was almost completely inhibited in the indomethacin group at all of the incubation times and was partially inhibited in the AA-861 group during the initial 3-5 minutes. Endogenous 5-lipoxygenase products generated in the early stages of incubation seem to be involved in PGI2 production in guinea-pig lungs. PMID- 1409768 TI - Histopathological evidence of protective action of garlic against collagen and arachidonic acid toxicity in rabbits. AB - Soluble rat tail tendon collagen produced respiratory distress, agitation, convulsions and finally death in rabbits when infused intravenously (i.v.) in lethal doses. Similar observations were noted when a lethal dose of arachidonic acid (unsaturated essential fatty acid) was infused. These agents caused thrombocytopenia, indicative of in vivo platelet aggregation, hypotension and increased levels of thromboxane (TX) B2 (a stable metabolite of TXA2) in the plasma. Histopathological examination of lung, heart and liver tissue indicated that the lungs and livers of treated animals were adversely affected, while heart tissues appeared to be normal. Histopathological examination of lung and liver tissues of animals pretreated with garlic, then treated with a lethal dose of collagen or arachidonic acid showed a significant reduction in the damage observed compared to animals not pretreated with garlic. PMID- 1409769 TI - Testosterone stimulates prostanoid production by rat vas deferens. AB - The rat isolated vas deferens produces and releases prostanoids into an incubation medium. Production of these substances from the exogenous precursor 14C arachidonic acid was studied in prepubertal, pubertal and adult animals. Synthesis of prostaglandin F, prostaglandin E, prostaglandin D and thromboxane B2 is lower in prepubertals arid increases significantly in pubertals, with no further modifications in adults. Castration of pubertals and adults dramatically reduces the production of all measured arachidonic acid metabolites but does not modify it in prepubertals. Replacement therapy with testosterone propionate significantly enhances prostanoid production in pubertal and adult castrated rats. Similar treatment on normal prepubertals also increases synthesis, indicating that androgens could be modulators of prostanoid synthesis in vas deferens. The lower effects obtained treating castrated adults with progesterone and with 17-beta estradiol suggest an action, at least partially specific for androgenic steroids. It is concluded that prostanoid production by the rat vas deferens from an exogenous precursor is closely related to the presence of androgens. PMID- 1409770 TI - The cumulative dose response effect of eicosapentaenoic and docosahexaenoic acid on blood pressure, plasma lipid profile and diet pattern in mild to moderate essential hypertensive black patients. AB - In this study eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were given in a cumulative manner, every 6 weeks, starting with 10 mg, then 100 mg, 1000 mg and 10,000 mg EPA daily to mild to moderate essential hypertensive black patients. The corresponding DHA doses were 3, 33, 333 and 3333 mg. A control group was given olive oil as placebo for the entire 24 weeks. The placebo group had lower diastolic and systolic blood pressures after 24 weeks than the EPA and DHA group. No effect was seen on plasma triglycerides, cholesterol, HDL cholesterol and gamma-glutamyltranspeptidase at any stage of the trial. In the EPA group plasma free-EPA increased significantly from 1000 mg onwards and plasma free-arachidonic acid (AA) decreased after 1000 mg EPA. No other plasma free essential fatty acid changed during the trial, although the HDL:cholesterol increased slightly but non-significantly with an increase in EPA and DHA. No significant changes in diet pattern or body mass was observed. It is therefore concluded that EPA and DHA supplementation had no beneficial effects in mild to moderate essential hypertensive black patients except for a lowering of plasma AA. PMID- 1409771 TI - Arachidonic acid channelling in the phospholipid fractions and subcellular compartments of cultured myocardial cells. AB - Arachidonic acid (AA) channeling in cultured heart cells was studied following pulse labelling for 1 h. AA was shown to be esterified immediately and equally distributed between the neutral lipids and phospholipids. A rapid constant flow to various phospholipid classes occurred thereafter, while the AA oxidation was only between 12%. The subcellular distribution of AA was studied by nitrogen cavitation followed by fractionation on 6.7% percoll in sucrose-EDTA. After 1 h pulse labeling and 2 h post-pulse incubation, most of the radioactivity was found in the sarcolemmal fraction with a much smaller amount in the mitochondrial fraction. PMID- 1409772 TI - Effects of D1 and D2 dopamine antagonists on behavior of polydipsic rats. AB - The behavioral and neurochemical effects of SCH3390 (SCH), a dopamine (DA) D1 antagonist, and haloperidol (HAL), a DA D2 receptor antagonist, on schedule induced polydipsia (SIP) were examined. Once animals were made polydipsic, a vehicle or one of three doses of SCH or HAL were administered to seven groups of rats in a series of three five-session blocks in a drug condition, no-drug condition, drug condition design. Detailed behavioral measures and brain regional levels of monoamine neurotransmitters and their major acidic metabolites were analyzed. The volume of water consumed and the percent of time spent drinking was reduced dose dependently by both SCH and HAL. As drinking decreased, the time spent chewing increased for both drugs. The total amount of time animals engaged in all oral behaviors was not changed, suggesting that chewing was substituted for drinking. Neurochemical analysis revealed that HAL increased striatal DA significantly. The polydipsic paradigm may be an advantageous model for examining neuroleptics due to SIP's sensitivity to extrapyramidal side effects. PMID- 1409773 TI - Effects of the beta-carboline abecarnil on epileptic activity, EEG, sleep and behavior of rats. AB - The profile of the anxiolytic beta-carboline isopropyl 6-benzyloxy-4 methoxymethyl beta-carboline-3-carboxylate (abecarnil; ZK 112 119), a partial agonist at benzodiazepine receptors, was determined in two experiments. In the first, abecarnil was given to WAG/Rij rats; these rats generate spontaneously occurring spike-wave discharges and are regarded as a model for absence epilepsy. Effects were measured on epileptic activity, together with those on the spectral content of the background electroencephalograph (EEG), as well as on ongoing behavior. In a second experiment, effects on sleep and behavior were investigated in Wistar rats. It was found that, similarly to classical benzodiazepines, abecarnil possessed a strong antiepileptic character and also changed the background EEG to more high-frequency waves and less spindle activity. It also produced more immobile behavior. Abecarnil induced only small, marginally significant increases in slow-wave sleep while reducing REM sleep as a proportion of total sleep. It also reduced the number of REM periods. These observations are consistent with the proposed partial agonist activity of abecarnil, a drug with interesting therapeutic implications. PMID- 1409774 TI - Behaviors induced by 5-hydroxytryptophan in neonatal, preweaning, postweaning, and adult Sprague-Dawley rats. AB - The behaviors induced by the 5-hydroxytryptamine (5-HT) precursor 5 hydroxytryptophan (5-HTP) has been called the "5-HT (serotonin) syndrome." These behaviors and others identified in rat pups were observed following administration of 5-HTP (300 mg/kg, SC) on postnatal (PN) days 3, 14, and 28 and in adult rats. Certain 5-HT syndrome behaviors and other uniquely neonatal behaviors were present in PN3 pups treated with vehicle. 5-HTP-treated PN3 pups showed increased head-shakes, rollovers, vocalizations, and forepaw treading and decreased hindlimb abduction. No 5-HT syndrome or neonatal behaviors were present at PN14 or PN28 or in adults treated with vehicle. 5-HTP administered at PN14 stimulated circling, forepaw treading, and resting tremor; at PN28, stimulated head-shakes and resting tremor; and in adults produced only head-shakes. To determine if prior exposure to 5-HTP affected the sensitivity of 5-HT receptor subtypes, the 5-HT1A agonist (+/-)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) and the 5-HT2/1C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were administered to all rats as adults. 8-OH-DPAT (1 mg/kg, SC) produced flattened body posture unaffected by prior exposure to 5-HTP. Head-shakes induced by DOI (5mg/kg, IP) were decreased by prior exposure to 5-HTP at PN3 and adult, but increased by preexposure at PN28. Thus, serotonergic neural systems are implicated in some behaviors of neonates. The developmental patterns suggest changes in the sensitivity to these systems. Further, lasting changes in 5-HT2/1C receptor sensitivity occur due to exposure to 5-HTP. PMID- 1409775 TI - Clorgyline-induced increases in presynaptic DA: changes in the behavioral and neurochemical effects of amphetamine using in vivo microdialysis. AB - Microdialysis was used in behaving rats to further characterize the behavioral and regional dopamine (DA) response to the monoamine oxidase (MAO) inhibitor clorgyline and determine how MAO inhibition affects amphetamine (AMPH)-induced changes in behavioral and extracellular DA dynamics. Although clorgyline (4.0 mg/kg) did not significantly alter behavior, it produced prolonged increases in caudate and accumbens extracellular DA and 3MT and corresponding decreases in homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Clorgyline pretreatment altered the behavioral response to both low (0.25 mg/kg) and moderate (2.5 mg/kg) doses of AMPH, which was characterized by a shift to more intense forms of stereotype and corresponding decreases in locomotion. The caudate and accumbens DA response to AMPH (0.25 mg/kg) was also significantly augmented, consistent with an increase in AMPH-releasable cytoplasmic DA. Thus, the potentiated DA response in clorgyline-pretreated animals may be responsible for the changes in the stereotypy profile. Possible implications of these observations for the augmented behavioral response observed with repeated AMPH administration are discussed. PMID- 1409776 TI - Effects of lithium and purinergic compounds on the behavioral and physiological aspects of restraint stress in rats. AB - This study investigates the effects of lithium and caffeine on psychomotor activities, defecation, and gastric lesions induced by restraint stress. Rats exposed to restraint stress typically exhibited a biphasic response consisting of an initial hypermotility (such as tail-flipping, body-rolling, jaw movement, and vocalization) accompanied by defecation, and followed by hypomotility (decrease in motility) accompanied by gastric ulceration. Lithium chloride (150 micrograms, ICV; 50 and 100 mg/kg, IP) significantly attenuated these responses while N6 cyclohexyl adenosine (CHA; 1.5 micrograms, ICV; 0.3 mg/kg, IP), a potent adenosine A1 receptor agonist, attenuated the behavioral effects but potentiated the gastric ulceration. Caffeine (3 micrograms, ICV; 1.0 mg/kg, IP), an adenosine receptor antagonist, inhibited the effects of CHA in animals exposed to 3 h of stress, but aggravated the effects in animals exposed to 6-12 h of stress. These results suggest that caffeine consumption may produce supersensitivity of adenosine receptors, which potentiate the actions of adenosine or CHA. Lithium may modulate the effects of stress by indirectly inhibiting central adenosine receptor activity. PMID- 1409777 TI - Temporal characteristics of appetitive stimulus effects of luteinizing hormone releasing hormone in male rats. AB - Conditioned place preference, induced by intraperitoneal injections of 5 micrograms/kg luteinizing hormone-releasing hormone (LHRH), was studied by varying the interval between the injection of LHRH and the conditioning sessions. Place preference was investigated for five presession intervals (0, 15, 45, 75, and 120 min) in separate groups of gonadectomized male rats provided with a subcutaneous testosterone implant. It was shown that the presession interval is an important parameter in the development of LHRH-induced conditioned place preference. Place preference was not observed after conditioning with intervals of 0, 75, and 120 min. With 15 and 45 min, however, a reliable preference was induced by LHRH. This study provides insight into the onset and offset of the appetitive stimulus properties of LHRH in male rats. PMID- 1409778 TI - Chronic morphine fails to enhance the reward value of prefrontal cortex self stimulation. AB - Dopamine (DA) plays an important role in the rewarding effects of drugs of abuse and intracranial self-stimulation (ICSS). We previously reported that ICSS derived from the prefrontal cortex appears insensitive to the reward-enhancing effects of amphetamine, a drug that increases DA release and reward at other ICSS sites. In the present study, rats with prefrontal electrodes were tested to see if morphine (7.5 or 10.0 mg/kg, IP) given once per day for 10 days enhanced prefrontal reward as assessed with the curve-shift method. Morphine initially produced sedation; however, after 3-4 days response rates increased sharply while frequency thresholds were unaffected. These results demonstrate that morphine does not enhance prefrontal ICSS reward and provide further evidence that prefrontal brain stimulation reward does not display the same characteristics as other ICSS sites. PMID- 1409779 TI - Bilateral neurochemical changes induced by unilateral cerebral haloperidol administration: evidence for cerebral asymmetry in the rat. AB - Bilateral alterations in dopamine metabolism were determined in the striatum, olfactory tubercle, and frontal cortex of rats pretested for circling behavior. Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, and 5-hydroxyindole-3-acetic acid (5-HIAA) were measured by high performance liquid chromatography 15 min after right or left intracarotid infusion of haloperidol. Concentrations of DOPAC and HVA were significantly increased in the striatum and frontal cortex ipsilateral to the side of haloperidol infusion, regardless of whether it was right or left. In contrast, the concentrations of these metabolites were unchanged in the olfactory tubercle after a right side infusion, but bilateral increases were evident after a left side infusion. Higher levels of DOPAC and HVA were also apparent in the left striatum and olfactory tubercle after intravenous jugular administration of haloperidol. Dopamine levels were significantly lower in the left striatum and right olfactory tubercle after intravenous haloperidol infusions. 5-HIAA concentrations were higher in the left olfactory tubercle following left side infusions of haloperidol. These data indicate that unilateral cerebral administration of haloperidol induces asymmetric and side-dependent alterations in dopamine and serotonin metabolites. These differences appear to be due to intrinsic variations in the sensitivity to haloperidol, but are not associated with the direction of circling behavior. PMID- 1409780 TI - Selective antagonism of acute ethanol-induced motor disturbances by centrally administered Ro 15-4513 in mice. AB - Results of the present investigation demonstrated that Ro 15-4513 when given ICV selectively antagonized ethanol-induced motor disturbances at doses that did not produce motor incoordination and lacked proconvulsant activity. Ro 15-4513 in 10 , 15-, and 22-ng doses antagonized, roughly in a dose-dependent manner, ethanol induced motor incoordination. The 10-ng dose produced an optimal effect with nearly complete antagonism within 30 min postethanol. The higher, 15 and 22 ng, doses of Ro 15-4513 antagonized, as well as probably reversed, ethanol-induced motor incoordination. The stimulation and inhibition of spontaneous motor activity by 1 and 2 g/kg IP ethanol, respectively, were also selectively antagonized by Ro 15-4513. Neither an alteration in the latency and/or duration of pentylenetetrazol-induced convulsions nor an antagonism to sodium pentobarbital-induced motor incoordination and inhibition of spontaneous motor activity by Ro 15-4513 at dose levels that showed antiethanol effects were observed. Only the 150-ng dose of Ro 15-4513, which exhibited intrinsic activity as proconvulsant, attenuated sodium pentobarbital-induced motor incoordination. When given alone at doses higher than those used in motor coordination experiments, Ro 15-4513 markedly increased spontaneous motor activity dose dependently. PMID- 1409781 TI - Cocaine-induced suppression of renin secretion is partially mediated by serotonergic mechanisms. AB - Acute cocaine reduces renin secretion. To determine whether serotonergic neurons mediate this effect, male Sprague-Dawley rats received the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (75 micrograms/side, ICV) 2 weeks prior to cocaine injections (3.75-15 mg/kg, IP). 5-HT lesions attenuated the cocaine induced reduction of plasma renin concentration (PRC), suggesting a partial 5-HT role. To determine which receptors mediate this response, rats were pretreated with the partial 5-HT1A agonist 8-[2-[4-(2-methoxyphenyl)-l-piperazinyl]ethyl]-8 azaspirol-[4,5]- decane-7,9-dione (BMY 7378) (1 mg/kg, SC), the 5-HT1C/5-HT2 antagonist ritanserin (0.1 mg/kg, SC), or the alpha 2/5-HT1A antagonist yohimbine (1 mg/kg, SC) prior to cocaine. None of the antagonists altered the cocaine induced suppression of PRC, although BMY 7378 and yohimbine elevated PRC. The data suggest that cocaine's effect is partially mediated by a serotonergic mechanism, but do not support a role for 5-HT1A receptors, 5-HT2/5-HT1C receptors, or alpha 2-adrenoceptors in mediating the suppressive effect of cocaine on renin secretion. PMID- 1409782 TI - Cocaine in utero enhances the behavioral response to cocaine in adult rats. AB - The effects of cocaine exposure in utero on cocaine-induced behaviors and dopamine (DA) transmission in the nigrostriatal and mesolimbic pathways were measured in adult rats. Pregnant rats received either saline or cocaine (1 or 3 mg/kg, IV) daily throughout gestation. When offspring were 3 months of age, locomotor and stereotypic behaviors were rated after an injection of either saline or cocaine (10 mg/kg, IP). Cocaine in utero increased the response to cocaine in adult offspring and increased basal locomotion in female offspring. Cocaine in utero increased amphetamine-stimulated release in female offspring but decreased release in males. On the other hand, male rats that had received cocaine in utero exhibited greater basal tritium release. One injection of cocaine increased amphetamine-stimulated [3H]DA release from striatal slices of male rats but not female rats. Neither cocaine in utero nor in vivo affected D2 DA receptor binding in striatum nor nucleus accumbens. Thus, cocaine in utero behaviorally sensitized animals to subsequent cocaine exposure and increased [3H]DA release from nigrostriatal endings, but the relationship of these two variables depended upon gender. PMID- 1409783 TI - Paradoxical effect of flurazepam. AB - Cold water swim stress has been shown to decrease the ability of flurazepam, a prototypic GABA-positive benzodiazepine, to antagonize the electrical precipitation of seizures in mice. This stress-induced reduction in the antiseizure efficacy of flurazepam is not due to a reduction in the threshold voltage for seizure production. In this study, we examined the effect of treating mice with flurazepam 20 min prior to cold water swim stress on its ability to antagonize electrically precipitated seizures 24 h later. Contrary to our expectation, pretreatment with flurazepam potentiated the stress-induced reduction of its antiseizure efficacy. PMID- 1409784 TI - MDL 73,147EF, a 5-HT3 antagonist, facilitates latent inhibition in the rat. AB - Latent inhibition (LI) is a behavioral model of selective attention that has been used to study the attentional deficits seen in schizophrenia. In the present study, we examined the effect of 5-hydroxytryptamine3 (5-HT3) receptor blockade on LI using the conditioned emotional response (CER) procedure. Prior exposure to 20, 30, or 40 stimulus presentations significantly, and almost completely, inhibited the CER to that stimulus. This LI effect was much weaker when only 10 preexposures were given. 1H-indole-3-carboxylic acid, trans-octahydro-3-oxo-2,6 methano-2H-quinolizin-8-yl ester methanesulfonate (MDL 73,147EF), a selective 5 HT3 receptor antagonist, significantly facilitated the LI effect observed after 10 preexposures at 0.1 mg/kg but not at 0.01 mg/kg. The magnitude of this effect was comparable to that observed with the classical neuroleptic haloperidol (0.1 mg/kg). Neither MDL 73,147EF nor haloperidol affected the CER in animals not preexposed to the stimulus. These results strongly corroborate suggestions that 5 HT3 receptor antagonists will be of use in the treatment of schizophrenia. PMID- 1409785 TI - [Leu]enkephalin and its metabolite, Tyr-Gly-Gly, impair active avoidance retention. AB - The current study examined the effects of [leu]enkephalin and its metabolite, Tyr Gly-Gly, given immediately posttraining on active avoidance performance measured 24 h later. Initial experiments revealed that, in comparison to zero or one training trials, providing mice with two training trials significantly increased active avoidance performance measured 24 h later; this enabled us to examine the effects on retention of peptides administered immediately after the two training trials. It was found that Tyr-Gly-Gly (16 and 53 micrograms/kg) and [leu]enkephalin (30 and 100 micrograms/kg) administered in this fashion both significantly impaired retention; the dose-response functions for both peptides were U-shaped. Since the effects of enkephalins are most likely mediated by opioid delta-receptors, and Tyr-Gly-Gly has little or no activity at opioid receptors, the effects of the parent peptide(s) and metabolite are presumably pharmacologically distinct. PMID- 1409786 TI - Further evidence showing that the inhibitory action of serotonin on rat masculine sexual behavior is mediated after the stimulation of 5-HT1B receptors. AB - To explore whether the inhibitory actions of endogenous serotonin on rat male sexual behavior were mediated via the stimulation of the 5-hydroxytryptamine1A (5 HT1A) or 5-HT1B receptor subtypes, two series of studies were undertaken. In the first series, an attempt to block the inhibitory actions of threshold doses of the serotonin precursor 5-hydroxytryptophan (5-HTP, 50 mg/kg) by administering the beta-5-HT antagonist alprenolol (5.0 mg/kg) and the selective beta-blocker practolol (0.5 mg/kg) was made. Both antagonists effectively prevented, at least partially, the inhibitory actions of 5-HTP. In the second series, a possible synergistic effect of a subthreshold dose of 5-HTP (12.5 mg/kg) with low doses of the selective 5-HT1B agonist 1-(m-trifluoro-methylphenyl)piperazine (TFMPP,0.125 mg/kg) or the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8 OH-DPAT, 0.0625 mg/kg) was investigated. A clear synergistic inhibitory effect of 5-HTP with TFMPP was observed. All data are interpreted based upon the hypothesis suggesting a physiological inhibitory role of the 5-HT1B receptor subtype on male rat sexual behavior. PMID- 1409787 TI - Morphine hyperalgesic effects on developmental changes in thermal nociception and respiration in domestic fowl (Gallus gallus). AB - Domestic fowl tested at 3, 5, and 7 days posthatch jumped from a heated grid more rapidly than animals tested at 14 days posthatch. Morphine (2.5 mg/kg) decreased jump latency in 14-day-old chicks but did not significantly affect jump latency in younger chicks. Respiration was lower in 3-day-old chicks than in the older groups but morphine depressed respiration at each age. In a second experiment morphine significantly decreased jump response latency in 5-day-old chicks when thermal stimulus intensity was lowered and morphine dose increased (5 mg/kg). Posttest respiration rate was depressed by morphine. Morphine hyperalgesia and respiratory depression were reversed by naloxone (5 mg/kg). However, naloxone alone increased jump response latency. Young domestic fowl are more sensitive and/or reactive to a noxious thermal stimulus and are less sensitive to morphine than 14-day-old chicks but morphine hyperalgesia was evident in both 5- and 14 day-old chicks. These hyperalgesic chicks may be tolerant at birth to morphine hypoalgesic effects on nociception. PMID- 1409788 TI - The 5-HT1A agonist 8-OH-DPAT attenuates the satiating action of cholecystokinin. AB - To investigate the dependence of the satiating action of cholecystokinin (CCK) on serotonergic action at central 5-HT receptors, we examined the effect of systemic pretreatment with 8-OH-DPAT (a 5-HT1A agonist that decreases central 5-HT synthesis and release via an action at somatodendritic autoreceptors in the brainstem raphe) on the suppression of food intake induced by systemic administration of cholecystokinin octapeptide (CKK-8). 8-OH-DPAT significantly attenuated the satiating action of CKK-8. This result is consistent with the hypothesis that peripherally acting CCK recruits central serotonergic processes to elicit normal satiety. PMID- 1409789 TI - Effects of calcitonin gene-related peptide on extrapyramidal motor system. AB - The effects of central administration of calcitonin gene-related peptide (CGRP, 1 or 100 ng/rat) on behavioral and biochemical parameters related to the extrapyramidal motor system were investigated in male rats. The peptide-induced catalepsy occurred only at the dose of 100 ng/rat and hypomotility at both doses used. Calcitonin gene-related peptide increased haloperidol-induced catalepsy and decreased apomorphine-induced hypermotility at the doses of 1 and 100 ng/rat. Although these behaviors are related to dopamine, no significant change of striatal DA or DOPAC concentration were observed after central administration of the peptide. Other neurotransmitters may be directly or indirectly involved in these behavioral effects of CGRP. PMID- 1409790 TI - Measurement of temperature in the rat by rectal probe and telemetry yields compatible results. AB - The change in body temperature of the rat is commonly measured using biotelemetry or the rectal probe. The authors report that the two methods yield qualitatively similar but quantitatively different results in two experiments. In Experiment 1, both methods detected a salicylate-affected reduction in handling-induced hyperthermia. In Experiment 2, both methods were useful in detecting the hypothermia induced by the muscarinic agonist oxotremorine. In both Experiments 1 and 2, measurements of baseline temperature were higher when measured with the rectal probe. Baseline temperature is measured with biotelemetry prior to handling animals, whereas the act of measuring baseline temperature with the rectal probe necessitates handling. The investigators hypothesized that a rise in baseline temperature produced by handling at least partially accounts for the greater hypothermic response obtained in Experiment 2 using measurements obtained with the rectal probe. In Experiment 3, baseline temperature was measured with biotelemetry after animals were handled. Handling produced an increase in baseline temperature. The hypothermic response to oxotremorine was increased when the higher posthandling baseline temperature was used to calculate the hypothermic response of animals. The authors conclude that differences in baseline temperature and hypothermic response obtained with the two methods are related to an effect of handling. PMID- 1409791 TI - Clozapine increases breaking points on a progressive-ratio schedule reinforced by intravenous cocaine. AB - The effect of the atypical neuroleptic clozapine on cocaine self-administration reinforced on a progressive-ratio schedule in rats was examined. The rat's first response on a lever each day produced an IV infusion of cocaine (0.6 mg/injection) after which the requirements of the schedule escalated with each infusion until the frequency of responding on the lever fell below a criterion level. The final ratio completed was defined as the breaking point. Doses of 5 and 20 mg/kg clozapine produced either no effect or a nonspecific disruption in responding. Rats pretreated with 10 mg/kg clozapine responded to significantly higher breaking points, indicating an increased motivation to self-administer cocaine. PMID- 1409792 TI - Long-term influence of d-amphetamine on mesolimbic brain-stimulation reward: comparison to chronic haloperidol and naloxone effects. AB - Rate-intensity functions for brain-stimulation reward from the dopamine (DA) A10 cell region of the ventral tegmental area (VTA) were assessed following chronic exposure to d-amphetamine (10.0 mg/kg), haloperidol (1.0 mg/kg), and naloxone (20.0 mg/kg). A reward depression developed when animals were tested daily 24 h following injection of amphetamine and haloperidol. In the case of amphetamine, this effect was transitory and a full recovery of intracranial self-stimulation (ICSS) was evident 5 days after drug abstinence. Low-dose (0.5 mg/kg) amphetamine challenge administered 50 days postdrug treatment decreased current thresholds indicating a long-lasting sensitization of mesolimbic reward processes. The reward depression induced by chronic haloperidol exposure showed no signs of recovery during the abstinence period and ICSS rates remained significantly reduced after amphetamine challenge 50 days later. These behavioral observations suggest that under conditions of continued demand the functional aspects of neuroleptic-induced depolarization inactivation of VTA neurons are enduring. Chronic exposure to naloxone did not modify reward thresholds indicating that opioid hypoactivity may not be a factor in the ICSS depression induced by long term amphetamine and haloperidol treatment. These data were related to the possibility that stimulant-induced sensitization of motivational processes may evolve as a compensatory response to the transitory development of withdrawal depression. PMID- 1409793 TI - Prazosin attenuates the effects of cocaine on motor activity but not on schedule controlled behavior in the rat. AB - The spontaneous motor activity of rats was measured following administration of cocaine alone and in combination with the centrally acting alpha 1-antagonist prazosin. Cocaine alone (18-42 mg/kg) increased motor activity in a dose-related manner. At doses of 1 and 1.8 mg/kg, prazosin attenuated the increases in motor activity produced by cocaine. In rats responding under a fixed-ratio discrimination procedure, cocaine (10-32 mg/kg) produced dose-dependent increases in percent errors and decreases in overall response rate. Across a range of doses (0.32-3.2 mg/kg), prazosin failed to antagonize the effects of cocaine on responding under the discrimination procedure. Rather, the combined effects were frequently greater than those obtained with cocaine alone. The data suggest that in rats activation of alpha 1-adrenergic systems may mediate the effects of cocaine on motor activity but not on schedule-controlled behavior. PMID- 1409794 TI - Decrease in cold tolerance of aged rats caused by the enhanced endogenous adenosine activity. AB - During severe cold exposure, old rats (24-28 months) were less capable of maintaining their body temperature compared to young rats (3-6 months) due to lower rate of heat production. Single injection of adenosine deaminase (AD) (converts adenosine to inosine) significantly increased thermogenesis in both young and old rats. However, doubling the dose of AD was required for optimal thermogenic response in old rats. In contrast, the similar enhancements in both thermogenesis and cold tolerance were observed in both young and old rats receiving the same optimal doses of specific adenosine receptor antagonists. These results lead to the suggestion that the lower capability of aged rats to withstand cold exposure could be due to an increase in adenosine stimulation because of the decreased endogenous AD activity rather than an increase in adenosine receptor sensitivity. This notion is further supported by the finding that the AD activity in the neck muscle, a key site for shivering thermogenesis, was significantly lower in old rats as compared to their younger counterparts before and after cold exposure. PMID- 1409795 TI - Effects of physostigmine on novelty-related location preferences. AB - Novelty-related location preferences and activity in an exploration box were recorded for male and female Wistar albino rats following intraperitoneal injections of 0.04 or 0.08 mg/kg of either physostigmine or neostigmine. Although rearing was reduced by the highest dose of both drugs and ambulation was reduced by the same dose of neostigmine, neither agent affected the significant preferences for novelty that typified all subjects. In a second experiment designed to assess the effects of 0.08 mg/kg of the two drugs administered during rather than after confinement to the familiar half of the apparatus, neostigmine reduced rearing, walking, and ambulation while increasing defecation, but physostigmine did not affect any response. While some minor motor impairment may have arisen from its peripheral effects, the lack of changes in novelty-related location preferences failed to support facilitation of either novelty avoidance or habituation by physostigmine suggested in previous studies. PMID- 1409796 TI - 5-HT1A and 5-HT2 receptors mediate discrete behaviors in the Mongolian gerbil. AB - Although the ability of agonists at specific serotonin (5-HT) receptor subtypes to induce distinct behaviors has been well documented in the rat, similar studies have not been reported in the Mongolian gerbil. We have found that the 5-HT1A/5 HT2 agonist 5-methoxy,N-N dimethyltryptamine (5-MeODMT) (0.5-8 mg/kg, SC), the specific 5-HT1A agonist 8-hydroxy(di-n-propylamino)tetralin (8-OH-DPAT) (0.125-16 mg/kg, SC), and the 5-HT precursor L-5-hydroxytryptophan (L-5-HTP) (100-250 mg/kg, SC) all elicit a 5-HT syndrome in the gerbil. This syndrome, analogous to the 5-HT syndrome in the rat, consists of reciprocal forepaw treading (RFT), hindleg abduction (HA), body tremors (BT), and Straub tail (ST). The putative 5 HT1A antagonist NAN-190 (0.25-8 mg/kg, SC) when dosed 15 min prior to either 5 MeODMT (4 mg/kg, SC) or 8-OH-DPAT (16 mg/kg, SC) blocked both RFT and HA in a dose-dependent manner, suggesting these 5-HT syndrome behaviors are mediated via 5-HT1A receptor activation. We also identified a unique, dose-responsive behavior in the gerbil, induced selectively by 5-HT1A agonists such as quipazine (2-16 mg/kg, SC) and (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.125-8 mg/kg, SC). This reciprocal hindleg body scratch (RHBS) behavior is dose dependently inhibited by pretreatment with the selective 5-HT2 antagonist ritanserin (0.0125-0.2 mg/kg, SC). RHBS behavior is also potently inhibited by pretreatment with the selective 5-HT1A agonist 8-OH-DPAT (0.005-0.04 mg/kg, SC), demonstrating a 5-HT1A/5-HT2 receptor subtype interaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409797 TI - Molecular mechanisms mediating the effects of L-alpha-glycerylphosphorylcholine, a new cognition-enhancing drug, on behavioral and biochemical parameters in young and aged rats. AB - The behavioral effects of the acute and subchronic administration of L-alpha glycerylphosphorylcholine (alpha-GPC) on passive and active avoidance behavioral tasks were investigated. When administered IP after training together with scopolamine 2 h before retest, alpha-GPC reverses the scopolamine-induced amnesia in the passive avoidance conditioning in young and old rats. Furthermore, the subchronic treatment with alpha-GPC positively and significantly influences the performance of both young and old animals in the active avoidance test. Moreover, in in vitro/ex vivo experiments alpha-GPC potentiates receptor-stimulated phosphatidylinositol hydrolysis in cortical synaptoneurosomes derived from young and old animals. In young but not old animals, alpha-GPC significantly potentiates potassium (40 mM)-stimulated intrasynaptosomal calcium oscillations in purified synaptosomes derived from the hippocampus. These results show that alpha-GPC improves the performance of animals in both active and passive conditioning tasks. Furthermore, subchronic treatment with the compound enhances in young and restores in aged animals the transduction of the signal, namely, the receptor-mediated production of inositol phosphate and the potassium-induced calcium mobilization. These modifications may represent at least part of the molecular mechanism of action of the compound. PMID- 1409798 TI - Effect of diazepam on successive negative contrast in one-way avoidance learning. AB - The effect of administration of diazepam on successive negative contrast in one way avoidance learning was examined in rats. Contrast was induced by shifting rats from a large reward, 30 s spent in the safe compartment, to a small reward, 1 s spent in the safe compartment. IP administration of 2 mg/kg diazepam eliminated this negative contrast. Moreover, this effect is dose dependent, with doses of 2 and 2.5 mg/kg, but not 0.5 mg/kg, effective in reliably reducing contrast. These results suggest the existence of similar or common underlying mechanisms in both aversive and appetitive contrast effects; they are discussed in light of the current theories of frustrative nonreward and as a mean of studying the behavioral and biological mechanisms of anxiety. PMID- 1409799 TI - Ethanol and circadian rhythms in the Syrian hamster: effects on entrained phase, reentrainment rate, and period. AB - Wheel-running rhythms were examined in male hamsters with access to 28% ethanol in lieu of water. One group was recorded in a light-dark (LD) cycle that was phase advanced by 8 h on three occasions separated by 23-27 days. On two of the three occasions, hamsters were subjected to a 2- to 3-h cage change procedure designed to stimulate wheel running, which accelerates the rate of reentrainment to 8-h advances. Ethanol and control hamsters showed no group differences in rhythm amplitude, entrained phase, or reentrainment rate. Both groups showed faster reentrainment in the cage change condition. A second group of hamsters recorded in constant dim showed a small but significant lengthening of the free running period of their wheel-running rhythm when provided with a 28% ethanol solution. Wheel running decreased during ethanol access in this group. Voluntary ethanol consumption evidently can slow the circadian pacemaker regulating activity rhythms in hamsters but has no measurable effect on photic entrainment or pacemaker response to LD shifts or nonphotic manipulations (stimulated activity). Period lengthening may be secondary to decreased activity, but other period-activity correlations obtained did not reveal a strong association between these two variables. PMID- 1409800 TI - Buspirone produces a dose-related impairment in spatial navigation. AB - Classical anxiolytic drugs and hippocampal lesions have common behavioural effects that include loss of place navigation in the water maze. The novel anxiolytic drug buspirone, unlike classical anxiolytic drugs, does not interact with GABA and is not muscle relaxant, sedative, hypnotic, anticonvulsant, or addictive. Buspirone affects hippocampal electrophysiology in a similar fashion to classical anxiolytics and so we predicted it would have similar effects on spatial navigation. Rats injected with buspirone (0.1-10.0 mg/kg, IP) showed a loss of acquisition of spatial navigation in the water maze that has a similar dose dependence to that reported for the effects of buspirone on the hippocampus. This finding demonstrates that the effects of anxiolytics on spatial navigation are not due to their side effects and supports the view that changes in hippocampal function may underlie some components of clinical anxiolytic action. PMID- 1409802 TI - Role of anxiety in subordinate male mice sexual behavior. AB - Dominant and subordinate male mice behave differently when exposed to a female, with subordinates showing impairment of their sexual performance in the presence of the male antagonist. In the present study, we investigate whether these rank related behavioral differences can be modified by an anxiolytic treatment. In a first experiment, diazepam (0.25 mg/kg) improves the performance of subordinate mice toward the female, as shown by the increase of proxemic behavior, anogenital sniffing, and social grooming of the female. Social grooming of the female is the only behavior modified by a higher dose of the anxiolytic drug (0.5 mg/kg). A second experiment, in which dominant and isolated mice are subjected to the same experimental procedure, demonstrates that social behavior of these two classes of males is not affected by the pharmacological treatment. The results are discussed in terms of the advantages of using subordinate males in such a sexual context as a model for the study of anxiolytic drugs. PMID- 1409801 TI - Possible link between brain serotonin metabolism and methionine sulfoximine induced hypothermia and associated behavior in the rat. AB - L-Methionine-D,L-sulfoximine (MSO) intraperitoneally or intracerebroventricularly (third ventricle) injected at convulsant doses induced a hypothermia, primarily associated with a syndrome of ataxia, in the restrained rat maintained at an ambient temperature of 23 degrees C. Depletion of brain serotonin (5-HT) by pretreatment with p-chlorophenylalanine (PCPA), p-chloroamphetamine (PCA), and d fenfluramine (FFA) did not significantly modify the time course and magnitude of MSO-induced developing hypothermia but it enhanced abnormal motor behavior. Enhancement of 5-HT synthesis in MSO-submitted rats pretreated with 5 hydroxytryptophan (5-HTP) (200 mg/kg, IP) alone or 5-HTP (100 mg/kg, IP) preassociated with carbidopa (10 mg/kg, IP) suppressed significantly hypothermia, but it did not greatly modify motor disturbances. In conclusion, the neurocytochemical processes initiating hypothermia following administration of MSO to the rat appear to be linked to a slowdown of the rate of brain 5-HT turnover, maybe at the level of the midbrain raphe nuclei. PMID- 1409803 TI - Oxytocin blocks the development of heroin-enkephalin cross-tolerance in mice. AB - The development of cross-tolerance to an analgesic effect has been observed between a mu-receptor agonist, heroin, and a delta-receptor agonist, Met2-Pro5 enkephalinamide. Repeated treatments with heroin twice a day for 4 days resulted in a decreased nociceptive effect to enkephalin on day 5. The enkephalin dose response line was shifted to the right, considered a sign of the development of cross-tolerance. Peripheral treatment with oxytocin blocked the development of heroin-enkephalin cross-tolerance. A similar effect was observed after intracerebroventricular administration of oxytocin, supporting our assumption that oxytocin blocks the development of heroin-enkephalin cross-tolerance via CNS mechanisms. PMID- 1409804 TI - Effects of atrial natriuretic peptide on acute and chronic effects of morphine. AB - Atrial natriuretic peptide (ANP) is known to participate in different vegetative functions. The aim of the present study was to investigate the influence of ANP on nociception itself, pain sensitivity to morphine, and the development of acute and chronic tolerance to morphine. Morphine withdrawal signs were also evaluated by injecting naloxone. In adult, male NMRI mice, ANP administered SC or ICV did not affect pain sensitivity itself in a heat-radiant tail-flick test. Peptide treatment, however, depressed the acute nociceptive effect of a single dose of morphine (4 mg/kg, SC) after both SC (20-200 ng/animal) and ICV (5, 10, 20, or 200 ng/animal) ANP administration. ANP given SC and ICV attenuated the development of acute morphine tolerance. Acute morphine tolerance was assessed by giving a bolus injection of morphine (60 mg/kg) 24 h before the pain sensitivity to a challenge dose of morphine (4 mg/kg) was measured. ICV treatment with ANP also blocked the development of chronic morphine tolerance, but did not affect the appearance of naloxone-precipitated withdrawal syndromes. ANP seems to act differently on the development of tolerance to and dependence upon morphine. PMID- 1409805 TI - Suppression of guinea pig ileum induced contractility by plasma albumin of hibernators. AB - Previous studies suggest that hibernation may be regulated by internal opioids and that the putative "hibernation induction trigger" (HIT) may itself be an opioid. This study examined the effect of plasma albumin (known to bind HIT) on induced contractility of the guinea pig ileum muscle strip. Morphine (400 nM) depressed contractility and 100 nM naloxone restored it. Ten milligrams of lyophilized plasma albumin fractions from hibernating ground squirrels, woodchucks, black bears, and polar bears produced similar inhibition, with partial reversal by naloxone. Five hundredths mg of D-Ala2-D-Leu5-enkephalin (DADLE) also inhibited contractility and naloxone reversed it. Conclusions are that hibernating individuals of these species contain an HIT substance that is opioid in nature and summer animals do not; an endogenous opioid similar to leu enkephalin may be the HIT compound or give rise to it. PMID- 1409806 TI - Amino acid levels during learning and memory consolidation of an aversive conditioning task in crickets. AB - We followed the titer of free amino acids in nervous ganglia and hemolymph of the cricket Pteronemobius sp. at different times during and after a shock avoidance training that included one experimental group and three controls. The results showed that Tau, urea, Thr, His, GABA, and an unidentified compound (Q) increased their titer in ganglia and hemolymph during training, whereas Ala, Arg, Val, Glu, Ser, and one or all of the group formed by Cys, Phe, Ile, Leu, and Trp decreased theirs concomitantly to memory consolidation. The difference in the rate of experimental insects and their yoked slaves to consolidate the learned task was reflected in the changes of the titers of the amino acids mentioned above. The data add to the evidence for a direct involvement of these amino acids in modulating the memory consolidation process. PMID- 1409807 TI - Effects of L-threo- and erythro-3,4-dihydroxyphenylserine on learning performance and concentrations of brain noradrenaline and its metabolites in rats. AB - Effects of L-threo and L-erythro-3,4-dihydroxyphenylserine [DOPS, precursor amino acids for noradrenaline (NA)] on the learning performance in a maze paradigm designed to model on the water maze paradigm using a multicomputerized behavioral analysis system were studied. A marked facilitation of learning performance was observed in rats after an intraventricular injection of 5 micrograms L-threo-DOPS (the s-NA precursor), and this effect was inhibited by a simultaneous administration of 1 or 2 micrograms propranolol (a beta-adrenergic antagonist). As concentrations of brain NA, 3-methoxy-4-hydroxyphenylglycol, and normethanephrine were increased by the injection of 5 micrograms L-threo-DOPS, the effect seemed to be derived from activation of beta-adrenoceptors in the CNS by the formed s-NA. On the other hand, an intraventricular injection of 5 micrograms L-erythro-DOPS (the r-NA precursor) attenuated the learning performance, and this effect was probably caused by the formed r-NA from L erythro-DOPS. PMID- 1409808 TI - Dehydroepiandrosterone enhances the hypnotic and hypothermic effects of ethanol and pentobarbital. AB - Recent reports have indicated that the neurosteroid dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) interact with the GABAA receptor complex. Because many of the behavioral effects of ethanol and pentobarbital are due to activity at this complex, DHEA and DHEAS were tested for their ability to interact with the hypnotic and hypothermic effects of ethanol and pentobarbital. DHEA, but not DHEAS, causes a dose-dependent increase in the sleep time induced by either ethanol or pentobarbital. At 20 mg/kg, DHEA and DHEAS themselves cause a fall in body temperature. DHEA enhances the hypothermic effect of both ethanol and pentobarbital. DHEAS enhances the hypothermic effect of ethanol, but with pentobarbital it only delays the return of body temperature to baseline levels. Neither DHEA nor DHEAS affects the metabolism of ethanol. PMID- 1409809 TI - Orally self-administered cocaine: reinforcing efficacy by the place preference method. AB - In three separate place preference conditioning (PPC) experiments, groups of rats were exposed to different modes of receiving cocaine: IP cocaine doses (7.5 mg/kg), PO cocaine self-administered bolus doses (15 mg/kg), and 1-h schedule induced cocaine-solution drinking sessions (19.1 mg/kg). Oral cocaine self administration of PO bolus and schedule induction took place in situations that preceded transfer into an apparatus for PPC sessions. Thus, the reinforcing efficacies of the pharmacological consequences of both oral cocaine self administration methods were evaluated by a procedure separate from the self administration behavior itself. The IP cocaine dose imposition and the two oral cocaine self-administration arrangements all resulted in dose-exposure conditions sufficient for the production of PPC. The serum and brain cocaine pharmacokinetics sufficient for the production of reinforcing efficacy were measured and related to previous data. PMID- 1409810 TI - Intermittent and continuous cocaine administration: residual behavioral states during withdrawal. AB - Rats were pretreated with 40 mg/kg/day cocaine for 14 days by either subcutaneous injections or osmotic minipumps. Rats were then withdrawn from the pretreatment regime for 1 or 7 days and given a 20-mg/kg IP cocaine challenge (day 1) or a 0-, 10-, 20-, or 40-mg/kg IP cocaine challenge (day 7). The results indicate that rats receiving intermittent, daily injections exhibited sensitization to the behavioral effects of a cocaine challenge on days 1 and 7 of withdrawal. In contrast, rats receiving continuous cocaine exhibited tolerance to the behavioral effects of a cocaine challenge on days 1 and 7 of withdrawal. The present results support and extend previous research that indicates that the route and temporal pattern of administration influences the effects of chronic cocaine. Furthermore, the present results indicate that the continuous infusion paradigm may represent an alternative animal model of some aspects of high-dose cocaine abuse, as compared to the typical procedure of single, or multiple, daily cocaine injections. PMID- 1409811 TI - Role of locus coeruleus and serotonergic drug actions on schedule-induced polydipsia. AB - Schedule-induced polydipsia (SIP) poses a general buffering property to reduce the heightened arousal produced by a schedule of intermittent feeding. It thus provides a unique opportunity to study CNS integration in stress-coping reactions. In the present study, we examined the role of the locus coeruleus (LC) and the pharmacological actions of serotonergic (5-HT2) analogs on SIP. Water intake, licking, and bar presses per minute in rats were recorded as indices of SIP activity after they had been subjected to 1-h performance of a fixed-interval 1-min operant pellet conditioning. Our results showed that SIP was progressively decreased after lesions were placed bilaterally in the LC areas and then followed by further lesioning in the bilateral ventral tegmental area. Neurotoxin DSP-4 also had an inhibitory action on the SIP potency. In addition, SIP was attenuated by 2,5-dimethoxy-4-iodoamphetamine (0.1, 0.5, or 1.0 mg/kg, IP), a 5-HT2 agonist, and activated by ritanserin (2.5 mg/kg, IP), a 5-HT2 agonist. After bilateral LC lesions, SIP was attenuated and the activating effect of RIT was abolished. Our data suggest that the LC is involved in the central integration of SIP and that the modulating effects of 5-HT2 receptors on SIP depend upon the integrity of LC function. PMID- 1409812 TI - Fearful behavior, body size, and serum IGF-I levels in nervous and normal pointer dogs. AB - Panic disorder in adult humans is associated with disturbances in hypothalamic growth hormone (GH) function and children with emotional deprivation or severe anxiety develop growth retardation. Nervous pointer dogs, a genetic animal model of panic disorder or severe anxiety, are characterized by extreme fearfulness and avoidance of novel stimuli. This experiment investigated indices of body stature, weight, and insulin-like growth factor I (IGF-I) levels in a colony of purebred nervous and purebred normal pointer dogs. The genetic line of nervous dogs had significantly greater scores of fearfulness, lower total body weights, lower weight/height ratio, and lower serum IGF-I levels than the normal line of pointer dogs. There was an inverse relationship between degree of fearfulness and total body weight in female, but not male, dogs. Stepwise logistic regression analysis indicated that the severity of fear behaviors, height, and weight were significantly associated with IGF-I levels. The best predictor of IGF-I levels in the dogs, however, was the severity of fearful behaviors elicited by exposure to novel stimuli and humans. These observations suggest that the neurobiological substrates of alarm, arousal, and fear influence hypothalamic-GH-somatomedin mediated effects on weight and, to a lesser extent, height. Findings are discussed in terms of their relevance to future research in humans with anxiety disorders. PMID- 1409813 TI - Effects of exercise on ethanol-induced hypothermia and loss of righting response in C57BL/6J mice. AB - C57BL/6J mice were given 5 weeks of voluntary wheel running and then studied for ethanol (EtOH) sensitivity as indicated by EtOH-induced hypothermia and loss of righting response (LORR) after 3.8 g/kg EtOH (20% w/v). Mice were assigned to wheel (free access to a running wheel in the home cage) or no wheel conditions, and wheel counts were monitored by a computer at 5-min intervals around the clock. In Experiment 1, duration of EtOH-induced LORR was assessed as amount of time required for the animal to right itself three times in a 30-s period, and body temperature was assessed by rectal probe. Wheel animals showed significantly shorter LORR and significantly less hypothermia at regaining the righting response than no wheel controls. In Experiment 2, temperature was assessed at 45 and 90 min after EtOH challenge. Baseline temperatures for wheel and no wheel animals did not differ, but wheel animals showed dramatic resistance to EtOH induced hypothermia at both time points. Together with our earlier work, these results provide evidence that prior exercise can offset the effects of EtOH intoxication in several domains of EtOH sensitivity. PMID- 1409814 TI - Picrotoxin-induced tonic-clonic seizures and lethality are decreased by MK-801 in developing rats. AB - The action of MK-801 (NMDA antagonist; 0.1 and 0.5 mg/kg, IP) was tested against picrotoxin-induced seizures (3-6 mg/kg, IP) in rats aged 7, 12, 18, 25, and 90 days. We found MK-801 only inconsistently affected clonic seizures in 12- and 25 day-old rats, whereas tonic-clonic seizures were suppressed or delayed in almost all age groups. In addition, the lethality of picrotoxin was diminished by the higher dose of MK-801 in all age groups. The results suggest: a) different generators for both seizure patterns (clonic and tonic-clonic), b) an involvement of NMDA receptors in the genesis of tonic-clonic seizure pattern, and c) an interaction of MK-801 with GABAergic transmission throughout the entire development studied. PMID- 1409815 TI - Differential effects of intrastriatal estradiol on the dorsal immobility response in male rats. AB - The effects of implants of 17 beta-estradiol and cholesterol in four regions of the dorsal striatum were tested on the duration of the dorsal immobility response in gonadectomized male rats. The dorsal immobility response was significantly potentiated by 4-h implants of 17 beta-estradiol in the dorsomedial and dorsolateral regions of the dorsal striatum but not in the ventromedial and ventrolateral regions. These data further support the growing evidence that estradiol acts directly but differentially on the striatum to affect behaviors in the rat. PMID- 1409816 TI - Conditioned activation induced by ethanol: role in sensitization and conditioned place preference. AB - Previous studies of ethanol-induced activation and place preference conditioning have shown that repeated exposure to ethanol produces sensitization to ethanol's locomotor activating effect in mice. This experiment was designed to determine whether the behavioral sensitization to ethanol that occurs during place preference conditioning is due to development of a Pavlovian conditioned activity response. Mice (DBA/2J) in the experimental group (BEFORE) received four pairings of a distinctive floor stimulus with ethanol (2 g/kg, IP); a different floor stimulus was paired with saline (counterbalanced). Mice in two control groups were exposed equally to each floor stimulus and were handled and injected as often as experimental mice. One control group (AFTER) always received ethanol in the home cage 1 h after exposure to the floor stimulus, while the other control group (NO-DRUG) never received ethanol during conditioning. BEFORE group mice showed a significant conditioned place preference, whereas control mice did not. Activity tests after saline or ethanol indicated higher activity levels in BEFORE mice compared to control mice, regardless of floor stimulus. Moreover, BEFORE mice were more active on their CS+ floor than on their CS- floor during saline tests; activity was equally elevated on both floors during ethanol tests. These results support the hypothesis that sensitization to ethanol's activating effect is mediated by Pavlovian conditioning. Further, they suggest that place conditioning established-associative control by two kinds of stimuli; the specific tactile cues serving as CS+ and CS- and the general environmental cues common to both CS+ and CS- trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409817 TI - Effects of centrally administered corticotropin-releasing factor (CRF) and alpha helical CRF on the vocalizations of isolated guinea pig pups. AB - Intraventricular corticotropin-releasing factor (CRF) was administered to guinea pig pups both with a freehand injection technique and via indwelling cannula. Behavioral effects depended upon the technique used. The highest dose of CRF (5 micrograms) inhibited the vocalizing of pups in a subsequent isolation test only when CRF was given by freehand injection. The possibility that disturbance attendant to the freehand procedure can account for this difference is discussed. To determine the effect of endogenous CRF in the absence of additional disturbance, the CRF antagonist alpha-helical CRF (ahCRF) was administered with the indwelling cannula procedure. ahCRF enhanced vocalizing during the first 10 min, and enhanced locomotor activity during the last 10 min, of a 30-min isolation test. Overall, the results indicate that endogenous CRF reduces vocalizing and locomotion during social isolation and that under certain injection conditions exogenous CRF can exacerbate the behavioral effect. The results also demonstrate the potential impact of the technique used to administer exogenous CRF. Further, the prevailing view, that CRF mediates stress-related behavioral responses, is supported only if behavioral inhibition, rather than vocalizing or locomotor activity, is viewed as the stress-related response in this situation. PMID- 1409818 TI - Oral cocaine self-administration: relation of locomotor activity to pharmacokinetics. AB - Rats were exposed to daily schedule-induced polydipsia sessions in which solutions of cocaine HCl were available. Both cocaine solution concentration (0.08-0.32 mg/ml) and session duration (0.25-3 h) were varied to determine their effects on locomotor activity rate. Additional animals were used to determine the effect of session length on serum cocaine and metabolite levels when drinking 0.32 mg/ml cocaine solution. Changes in locomotor activity rate were related to serum cocaine concentration by a linear concentration-effect model. By estimation from the linear model, the serum cocaine concentration threshold for increasing locomotor activity was about 0.01 microgram/ml. Under these schedule-induction conditions, there was no evidence for the development of acute tolerance to the locomotor-stimulating activity of cocaine. PMID- 1409819 TI - Chronic stress induces strain-dependent sensitization to the behavioral effects of amphetamine in the mouse. AB - Following 10 days of daily restraint stress, sensitization developed to the stimulatory effect of amphetamine on locomotion in DBA/2 but not in C57BL/6 mice tested 24 h after the last stressful experience regardless of their being naive or habituated to the test cages. Saline-injected C57BL/6 mice, however, showed an increase of locomotion 24 h after chronic stress treatment. Chronically stressed mice of the two strains did not exhibit any alteration of dopamine and metabolites (3-4-dihydroxphenylacetic acid, homovanillic acid, and 3 methoxytyramine) levels in the frontal cortex, caudatus putamen, or nucleus accumbens septi, thus ruling out that stress-induced alteration of basal dopamine metabolism affected the behavioral response to amphetamine challenging in DBA/2 mice. Ten daily amphetamine injections (5 mg/kg) did not significantly modify the behavioral response to amphetamine in either strain of mice tested 24 h after the end of the chronic treatment and did not increase locomotion in saline-injected C57BL/6 mice. Finally, chronically stressed hybrids B6D2F1 did not show sensitization to the locomotor effects of amphetamine, suggesting a dominant mode of inheritance in the response to chronic stress of the C57BL/6 strain. PMID- 1409820 TI - Learning-induced changes in D2 receptors of rat brain are sexually dimorphic. AB - Pharmacological agents known to stimulate monoamine systems improve memory, and destruction of the dopaminergic systems or dopamine depletion lead to impairments in various learning-related tasks. These reported effects of the central dopaminergic system imply the involvement of D2 receptors. The aim of the present study was to investigate changes in [3H]spiroperidol binding in seven areas of rat brain following informal and active avoidance learning. Littermate male and female rats were reared until 3 months of age in standard colony conditions and treated as active controls or in enriched environmental conditions and exposed to pole-jump active avoidance trials. Female rats acquired avoidance behavior more rapidly than males. Among the brain regions, only the hippocampus showed significant variations in D2 receptor binding between the groups; sex differences and learning-sex interaction were observed in the corpus striatum. There was an inverse correlation between learning performance and hippocampal D2 receptor binding. Our results show that learning affects hippocampal D2 receptors in a sexually dimorphic pattern. PMID- 1409821 TI - Effects of an inhibitor of GABA-aminotransferase (gamma-vinyl-GABA) on the spatial navigation deficit induced by muscarinic blockade. AB - The present study investigated whether stimulation of the GABAergic system affects spatial navigation [water-maze (WM)] deficit induced by muscarinic blockade (scopolamine). The effects of various doses of gamma-vinyl-GABA (GVG) (50, 150, and 300 mg/kg) and scopolamine (0.4 and 0.1 mg/kg) were examined alone and in combination. GVG at 50 and 150 mg/kg alone did not impair the performance of rats in the WM yask. At 300 mg/kg, GVG caused slight impairment, increasing latency and total distance swim during training trials. Scopolamine at 0.4 mg/kg clearly impaired the performance of rats in the WM task. When the two drugs were coadministered, no interaction between scopolamine and GVG was observed. Our results do not provide support for any interaction between cholinergic muscarinic and GABAergic mechanisms. PMID- 1409822 TI - Effect of Ro 15-4513 on ethanol-induced conditioned place preference. AB - The benzodiazepine receptor inverse agonist Ro 15-4513 reverses a number of ethanol's effects, including its reinforcing properties as measured through self administration. The present study examined the effect of this putative ethanol antagonist in a place conditioning design that has been shown to be sensitive to ethanol's rewarding properties in mice. Using an unbiased differential conditioning procedure, DBA/2J mice received, on alternate days, pairings of a distinctive floor stimulus (CS+) with either ethanol (2 g/kg), Ro 15-4513 (3 mg/kg), or a combination of ethanol and Ro 15-4513. On alternate days, a different distinctive floor stimulus (CS-) was paired with vehicle. Under these conditions, ethanol produced a conditioned place preference that was unaffected by Ro 15-4513. Ro 15-4513 alone did not produce either a place preference or aversion. Ro 15-4513 did produce reductions in locomotor activity during conditioning, indicating it was behaviorally active. These results indicate that a dose of Ro 15-4513 that alters general activity does not affect ethanol reward. PMID- 1409823 TI - [Pharmacokinetics in the aged]. PMID- 1409824 TI - Synthesis of condensed heterocycles from 3-aryl-2,4-dicarbethoxy-5 methylcyclohexanones and their testing for antimicrobial activity. AB - Condensation of the title compounds (1) with hydroxylamine hydrochloride, hydrazines and/or aromatic amines resulted in the formation of the benzisoxazoles 2, oximes 3, indazolines 4 and beta-keto anilides 6. The oxime derivatives and anilides underwent cyclization to compounds 2. The interaction between 1 and thiourea gave the benzothiazines 7 and thiouracils 8. Compounds 8 on treatment with monochloroacetic acid gave the dioxo compounds 9, while their reaction with hydrazine hydrate afforded the hydrazino derivatives 10, which upon treatment with nitrous acid gave the azido or tetrazolo derivatives 11 and 12. Treatment of 1 with 2,3-diaminopyridine and/or 2-amino-3-hydroxy-pyridine gave the pyrimidoquinazolines 13 or 14. Some of the synthesized compounds were screened to test their antimicrobial properties. PMID- 1409825 TI - Synthesis and biological activity of some heterocyclic systems containing anthraquinone. AB - 2-Aminoanthraquinone (1) was reacted with ethyl chloroformate to afford 2. The reaction between carbamate 2 and hydrazine hydrate gave semicarbazide 3, which on treatment with benzoic acid, phenyl isothiocyanate and carbon disulfide/potassium hydroxide furnished oxadiazoles 4, 6 and triazole 5, respectively. Also, treatment of 1 with chloroacetyl chloride gave chloroacetyl derivative 8. The reaction of glycolic acid, thioglycolic acid, diethyl malonate and malononitrile with 8 has been investigated. Compound 8 was treated with potassium thiocyanate to give 12, which was cyclized to 13a, while the reaction between 8 and potassium cyanate gave 13b directly. The structures of hitherto unknown compounds were confirmed by analytical and spectral methods. Some of the synthesized compounds were screened to test their antibacterial and antifungal properties. PMID- 1409826 TI - A rapid thin layer chromatographic procedure to identify poor and extensive oxidative drug metabolizers in man using dextromethorphan. AB - A rapid TLC method is presented to distinguish poor oxidative drug metabolizers from extensive oxidative drug metabolizers. Dextromethorphan (1) is used as test probe because it is safe, well characterized, generally available and easy to measure. The method is based on the extraction of 1 and its major oxidative metabolite dextrorphan (2) from urine, followed by separation on a TLC plate and visualized by a combined Marquis/Mandelin reaction. The intensities of the spots are then compared with a series of standard mixtures containing 1 and 2 in a ratio of 0.3 at different concentrations. This value represents the antimode that separates poor from extensive metabolizers, and an individual is identified as a poor metabolizer if the intensity ratio of the two spots from his urine sample is higher than 0.3. The proposed TLC method was cross checked with an HPLC method and found to correctly identify 9 poor metabolizers out of a population of 71 volunteers. PMID- 1409827 TI - Availability of phenindione-beta-cyclodextrin inclusion complex. AB - The inclusion complexation was occurred between beta-cyclodextrin (beta-CD) and phenindione (1) in aqueous solution. The complex formation was proved by solubility, dissolution and permeation study. The inclusion complex was prepared and its physicochemical properties was studied. 1 was combined with beta-CD in 1:1 molar ratio. Using the solubility data, the value of apparent stability constant obtained of 1/beta-CD complex was 492.7. The dissolution rate of 1 was increased in presence of beta-CD. The permeability coefficients of 1 were 7.86 x 10(-3), 4.76 x 10(-3) and 5.0 x 10(-3), corresponding to pure drug, its physical mixture with beta-CD and the inclusion complex, respectively. The presence of human albumin generally decreased the permeability coefficient of the drug. The reduction (79.5%) was found to be nearly equal in case of either pure 1 or its complex with beta-CD. Administration of 1 or its inclusion complex with beta-CD to rabbits increase prothrombin times, the effect was more pronounced in the complex form of drug than free one. PMID- 1409829 TI - Influence of leukemia P388 on plasma concentration-time profiles of bendamustine in B6D2F1 mice. AB - It was the aim of this study to investigate whether leukemia P388 being an important murine transplantation tumor may alter the plasma concentration-time profiles of the alkylating antineoplastic agent bendamustine (1) in mice. In an advanced tumor stage the rapid decline of 1 plasma levels was found to be retarded in tumor-bearing in comparison to tumor-free animals both after i.v. and p.o. drug administration. These changes cannot be explained by the neoplasia related depression of drug metabolism whereas the 1-containing ascitic fluid may be a possible reason for the prolonged drug levels in plasma. After p.o. administration of 1, the bioavailability of the drug was found to be increased in the leukemia-bearing animals. PMID- 1409828 TI - [2-Amino-oxazoles as potential H-bonding agents in virostatic research. 4. Pharmacokinetics and pharmacologic-toxicologic profile of 2-guanidino-4,5 dipropyloxazole hydrochloride]. AB - Out of the group of 2-amino-oxazoles 1 was found to be the most potent antiviral compound. Following p.o. or s.c. administration to rats, the 14C-labeled 1 was quickly and completely absorbed. The TRA was eliminated mainly via the kidneys and the liver with half-lives between 32 and 42 h. The acute pharmacodynamic effects of 1 were decrease of blood pressure, bradycardia, and inhibition of both gastric emptying and acid secretion. On smooth muscles spasmolytic and alpha-anti adrenergic actions were predominant. After single administration the following MTD's were determined: 30 (mouse), 20 (rat), 10 mg/kg i.v. (pig), and 500 (mouse, rat), greater than 100 mg/kg p.o. (pig), respectively. In a subchronic toxicity study in rats, oral doses of 1 between 15 and 240 mg/kg given daily for 4 weeks were tolerated without any severe alterations related to the drug. PMID- 1409830 TI - Deferoxamine (Desferal) improves the content of oxygen in myocardial tissues during recovery after hypoxia in isolated rabbit heart. AB - On isolated working right heart from rabbit tissue oxygen content as an indicator of function of oxygen transport and storage was observed by moderate hypoxia, hypoxia with deferoxamine (1) and iron infusion. In addition water content of myocardium as an indicator of metabolic damage was evaluated and the copper depletion was established. During the recovery the results presented a beneficial effect on the content of tissue oxygen which is due to 1. But the copper depletion was not changed. Possible connections are discussed. PMID- 1409831 TI - In vitro interaction of interferon-alpha-2b with microspheres particles. PMID- 1409832 TI - Dose-dependence of coumarin elimination and inhibitory effect of 8-methoxy psoralen. PMID- 1409833 TI - [Is propranolol suitable for the liver function test?]. PMID- 1409834 TI - Difference in the inhibition of plasma carboxylesterase activity by metoclopramide in humans and laboratory animals. PMID- 1409835 TI - Antiarrhythmic-antihypoxic drug stobadine inhibits copper-induced peroxidation of low density lipoprotein. PMID- 1409836 TI - The effect of the mushroom Pleurotus ostreatus on the lipid peroxidation of phosphatidylcholine liposomes. PMID- 1409837 TI - Modulation of adenosine deaminase activity of endothelial cells by steroids. PMID- 1409838 TI - Potentiating effect of 1,2,4-thiadiazolidines on barbiturate-induced hypnosis in albino mice. PMID- 1409839 TI - [New ampicillin derivatives with glyoxyloylbenzhydrazone side chains]. AB - New ampicillin derivatives were synthesized from glyoxylic acid benzhydrazones by reaction with chloroformates via mixed anhydrides and ampicillin. These compounds were tested in an agar diffusion test against six different bacterial strains and also for their stability against beta-lactamases. Studies about structure activity relationships have shown, that the activity against different bacterial strains is influenced in different manner by hydrophilic or hydrophobic and electronic properties of substituents. PMID- 1409840 TI - Pro-drugs of isoniazid: synthesis and diffusion characteristics of acyl derivatives. AB - The attachment of various acyl groups to the NH2 function of isoniazid afforded in good yields pro-drugs which were characterized by spectroscopic and analytical methods. The in vitro diffusion of pro-drugs was studied; the transfer rate constants from simulated gastro-intestinal juices to simulated plasma, through artificial wall lipid membranes were defined and compared with those of an equivalent dose of pure isoniazid. The diffusion rate constants were not greatly affected by the length of the substituent chain. All compounds were treated with artificial gastric or intestinal juices. No significant hydrolysis was observed. PMID- 1409841 TI - In vitro release, pharmacokinetic and tissue distribution studies of doxorubicin hydrochloride (Adriamycin HCl) encapsulated in lipiodolized w/o emulsions and w/o/w multiple emulsions. AB - The lipiodolized w/o emulsion or w/o/w multiple emulsion containing Doxorubicin hydrochloride (1; Adriamycin HCl) with different emulsifiers was prepared to evaluate in vitro sustained-release behavior, pharmacokinetic and tissue distribution function in Sprague Dawley (SD) rats. The results of dissolution indicate that the release of 1 was significantly sustained for both emulsions when HCO-60 (polyoxyethylene (60) hydrogenated castor oil) was used as an emulsifier. The serum concentration of 1 was reduced and prolonged for both emulsions with the increase of HCO-60. The C(max) level was lowered and T(max) value was delayed after administration of w/o emulsions with higher HCO-60 concentration. The apparent terminal half-life for 1 released from some emulsions with higher concentration of HCO-60 was 3-folds higher than that of the 1 solution. The clearance of some w/o or w/o/w ADR emulsions also decreased with the increase of HCO-60. Not only the concentration of 1 in heart and kidney decreased significantly after the administration of w/o emulsions with the higher concentration of HCO-60, but also the hepatic concentration of 1 was higher and increased with HCO-60 concentration. The hepatic 1 level became lower after administration of w/o/w multiple emulsions with the increase of HCO-60; however, the concentration of 1 in heart, lung and spleen increased somewhat. The results indicate that lipiodol and HCO-60 seemed to play an important role in the prolongation and selective retention of w/o emulsion or w/o/w multiple emulsion, in vitro and in vivo. PMID- 1409842 TI - Effects of isoniazid on hepatic drug oxidation and N-acetylation capacities in rats. AB - In vitro and in vivo activity of hepatic monooxygenase as well as in vivo N acetylation capacity were assessed in male Wistar rats after oral pretreatment with 10 and 50 mg/kg isoniazid for 7 d. Both doses of isoniazid showed no statistical difference in protein contents, total cytochrome P-450 and the activities of aminopyrine N-demethylase as well as ethoxyresorufin-O-deethylase in the 9000 x g liver homogenate suspension compared to the saline pretreated group. Body and relative liver weights remained also unchanged. In vivo isoniazid pretreatment with either dose hardly changed the kinetic profiles and parameters of phenazone and sulfadimidine (free + total). The results suggest that drug metabolizing pathways that can be evaluated by the metabolism of the model substances employed here may not be modified by prolonged isoniazid treatment. PMID- 1409843 TI - Protection of the hypoxic myocardium by the bispyridine derivatives AWD 122-14 and milrinone: studies on isolated, working right rabbit hearts. AB - Isolated rabbit hearts were perfused via the aortic root with Muralt solution at a constant perfusion pressure of 52 mm Hg ("preload"). After passing the coronary system, the right ventricle pumps the perfusion medium against an "afterload" of 5.15 +/- 1.3 mm Hg through the arteria pulmonalis with a spontaneous heart rate of 131 +/- 11 beats/min. In this model, the right ventricle works under "physiological" conditions. The model was characterized by applying the parameters of Doring et al. The following parameters of this model were measured: RVPsyst. + diast., Qpulm., MVO2, HR, dp/dtmax, dp/dtmin. By applying the method of Neely et al. the external pressure work (w), the efficiency (e) and the coronary resistance (R) were calculated. After a short period of hypoxia of 5 min (the pO2 in the perfusion medium was decreased from 530 mm Hg to 160 mm Hg), the ventricle functions are reversibly depressed, and restored partially under reperfusion (15 min) of the myocardium in dependence of the hypoxia and reperfusion lesions. The application of 3 x 10(-6) mol/l of the two bispyridine derivatives AWD 122-14 and milrinone into the perfusion medium during the total experimental time protected the myocardium partially against the hypoxia and reperfusion lesions. This protecting activity can be shown in a better preserve and recovery of the ventricle functions (pulmonalis flow, external pressure work, efficiency). The application of 5 x 10(-8) mol/l nifedipine, a known protective substance, showed a lower activity in this model compared with the activity of the bispyridines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409844 TI - Preparation of multi-chamber gastrointestinal diffusion system for isosorbide-5 mononitrate. PMID- 1409845 TI - Isolation and hypotensive activity of a polymeric procyanidin fraction from Pistacia lentiscus L. PMID- 1409846 TI - Antifungal activity of some essential oil isolates. PMID- 1409847 TI - Histamine H3 receptors are not involved in the regulation of rat gastric secretion. AB - The effects of histamine H3 receptor activation [(R)alpha-methylhistamine] and blockade (thioperamide) on rat gastric secretion were determined in vivo and in vitro. (R)alpha-Methylhistamine (0.1-5 mumol/kg i.p.) did not modify secretory volume and acidity in pylorus-ligated rats; it did not affect basal acid secretion and the secretion stimulated by histamine, pentagastrin and 2-deoxy-D glucose in the lumen-perfused stomach of anaesthetized rats, when administered by continuous infusion (0.01-1 mumol/kg/h) or bolus injection (0.05-25 mumol/kg). In this preparation, the H3 agonist increased acid secretion at doses of 3-25 mumol/kg i.v., the effect being antagonized by famotidine. In the isolated gastric fundus from immature rats both (R)alpha-methylhistamine (0.01-10 mumol/l) and thioperamide (0.01-1 mumol/l) were totally ineffective against both spontaneous and stimulated gastric secretion. These results suggest that histamine H3 receptors are unlikely to have a role in regulating gastric acid secretion in the rat. PMID- 1409848 TI - Characteristics of vasoinhibitory action of FK 453 (a pyrazolo-pyridine derivative), a new antihypertensive agent with diuretic action in isolated rabbit aorta. AB - The vasoinhibitory effect of FK 453 was examined in isolated rabbit aorta. FK 453 inhibited contractile responses to norepinephrine, angiotensin-I and KCl. Pretreatment of the tissue with FK 453 failed to affect the relaxing effect of verapamil on the KCl response and the inhibitory effect of prazosin on the phenylephrine response. FK 453 inhibited both the residual norepinephrine response and the subsequent Ca2+ response in a Ca(2+)-free medium containing EGTA and nifedipine. The inhibitory effect of a combined treatment with either FK 453 plus nitroglycerin or FK 453 plus theophylline, but not with FK 453 plus M & B 22,948 (2-o-propoxyphenyl-8-azapurine-6-one; May & Baker), was much greater than that of any single treatment. Pretreatment with FK 453 also potentiated relaxing effects of nitroglycerin and isoproterenol on the PGF2 alpha response. The effect of a combined treatment with FK 453 plus theophylline, but not with FK 453 plus M & B 22,948, was much greater than that of any single treatment. FK 453 also inhibited the activity of phosphodiesterase from canine aorta to convert cyclic [3H]-GMP and cyclic [3H]-AMP to 5'-GMP and 5'-AMP, respectively. These results suggest that the inhibitory action of FK 453 is not due to inhibition of voltage operated Ca2+ channels or alpha-adrenoceptors, but due to increase in cyclic GMP level. PMID- 1409849 TI - Microcomputer-aided system for electrocardiograms and blood pressure analysis during drug-induced transient periods. AB - In the current experiments, we have developed a microcomputer-aided system for amplitude and duration parameter analysis of electrocardiogram (ECG) and blood pressure (BP) waveforms during the drug-induced transient period. Both ECG and BP are monitored, amplified and recorded using standard techniques. For studying the parameter variation trend, the time course of each parameter was produced. Based on these requirements, the present system combined data acquisition, data selection, data analysis, graph plotting and some experimental techniques to meet the need. Generalized human ECG and arterial BP waveforms were used in this system to expand its usable ranges. From the time course graph plotting, the variation trend of each parameter during each drug-induced transient period was obtained thereafter. The main advantages of this system include: (1) transient analysis--the system is suitable for complete and precise parameter analysis of human and animal ECG and BP in the drug-induced transient period; (2) ease of construction--the simplified hardware interface and IBM PC-AT compatible system make this system easy to be constructed; (3) ease of operation--modular data acquisition, processing and analysis procedures make this system easy to be operated; (4) high expansion potential--the modular hardware interface and modular software procedure make this system easy to be expanded; (5) wide utility -the system can be applied to any other research areas which involve the parameter analysis of ECG and BP. PMID- 1409850 TI - Metabolic zonation of the liver: regulation and implications for liver function. AB - Liver parenchyma shows a remarkable heterogeneity of the hepatocytes along the porto-central axis with respect to ultrastructure and enzyme activities resulting in different cellular functions within different zones of the liver lobuli. According to the concept of metabolic zonation, the spatial organization of the various metabolic pathways and functions forms the basis for the efficient adaptation of liver metabolism to the different nutritional requirements of the whole organism in different metabolic states. The present review summarizes current knowledge about this heterogeneity, its development and determination, as well as about its significance for the understanding of all aspects of liver function and pathology, especially of intermediary metabolism, biotransformation of drugs and zonal toxicity of hepatotoxins. PMID- 1409851 TI - Serum-free cell culture. AB - Cell culture is one important tool when studying cellular functions and molecular biology. It is also a basic method in most virological investigations. Serum has been an obligatory component in most cell culture media. During the last decades serum-free, chemically defined media have been developed, that are supplemented with a number of substances with specific cellular activities. The main developments of defined media are presented. Examples are given of investigations with different cell types. PMID- 1409853 TI - Suffering, literature, and the art of medicine. PMID- 1409852 TI - Free radicals and other reactive oxygen metabolites in inflammatory bowel disease: cause, consequence or epiphenomenon? AB - Oxygen-derived free radicals and other reactive oxygen metabolites have emerged as a common pathway of tissue injury in a wide variety of otherwise disparate disease processes. This has given rise to the hope that efforts directed towards the pharmacologic control of free radical-mediated tissue injury (Reilly, P.M., Schiller, H. J. and Bulkley, G. B. (1991) Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am. J. Surg. 161: 488-503) may have particular application to patients suffering from Crohn's disease and/or ulcerative colitis. However, because tissue injury by any mechanism, even direct mechanical trauma, can elicit an inflammatory response which entails the secondary generation of toxic oxidants by neutrophils and tissue macrophages, it is important that the evidence for this association be examined critically, so as to discriminate the possibility of an etiologic role for these toxic compounds from their presence as a reflection of injury caused primarily by other agents. Similarly, in considering the therapeutic potential of free radical ablation for the treatment of patients with IBD it is important to distinguish between interventions that might specifically block the fundamental injury mechanism from those which would act in a more nonspecific, anti inflammatory role. PMID- 1409854 TI - Revelations and revolution: a medical student's trip to Haiti during the 1990 revolution. PMID- 1409855 TI - A 1992 manifesto for primary physicians. PMID- 1409856 TI - Should you operate on your own mother? PMID- 1409857 TI - The mad doctor in fiction. PMID- 1409858 TI - "The care of the patient": a living testimony to Francis Weld Peabody. PMID- 1409859 TI - Sad town, torn gown. PMID- 1409860 TI - Use of sexually explicit words in The Pharos. PMID- 1409862 TI - Another tenet for residents. PMID- 1409861 TI - Are medicine and education equal? PMID- 1409863 TI - Ideal family medicine. PMID- 1409864 TI - Music and medicine. PMID- 1409865 TI - Francois Rabelais: satire as therapy for the body politic. PMID- 1409866 TI - Haloperidol and reduced haloperidol serum levels: correlation with psychopathology in acute schizophrenia. AB - Serum levels of haloperidol (HPL) and reduced haloperidol (RHPL) as well as the RHPL/HPL ratio were determined in 55 acute schizophrenics on oral haloperidol medication and correlated over 28 days with psychopathology and extrapyramidal symptom scores. Linear and nonlinear models of serum concentration and psychopathology were tested at several time points. No single consistent model could be established for either HPL or RPHL. However, when non-parametrical methods are used HPL levels between 10 and 25 ng/ml can be shown to be significantly associated with better outcome during the first three weeks of treatment. RHPL is unsuitable for therapy monitoring, since equilibrium is not reached in the first four weeks of treatment. The RHPL/HPL ratio was found to rise continuously during the study, and it neither separated responders from nonresponders nor did it correlate with clinical outcome. PMID- 1409868 TI - Exacerbation of tics following antidepressant therapy in a case of Gilles-de-la Tourette syndrome. PMID- 1409867 TI - Quantitative topographical analysis of effects of single thiopental bolus on human electroencephalogram. AB - The aim of present study was to characterize the topographical effect of thiopental on the EEG during induction of anesthesia. A multichannel (19 channels) digital EEG was recorded in 10 patients undergoing surgical treatment. The period during induction of anaesthesia before intubation was investigated in regard to peak frequency, amplitude, topography, and amplitude in conventional frequency bands. The main findings were a slowing of the EEG with a simultaneous increase of amplitude in the predominant EEG frequency (peak frequency) during induction. The topographical analysis showed a clear change of localization of the peak frequency in the occipito-frontal direction. Berger described the effect of thiopental on electrical cortical activity as early as 1933. Since then, many studies have investigated its influence on the EEG, but few have tried to characterize the effects of topographical changes in a quantitative way. PMID- 1409869 TI - Fluvoxamine-induced acute exacerbation in residual schizophrenia. PMID- 1409870 TI - An absorptiometry method for the determination of arterial blood concentration of injected iodinated contrast agent. AB - A single photon absorptiometry method to measure the arterial concentration of injected iodinated contrast agent was developed. A prototype absorptiometry unit was built which consists of either a square or circular cross section acrylic (polymethylmethacrylate) cuvette connected to an arterial catheter at one end and a paristaltic pump at the other via PE60 surgical tubing. At opposing ends of the length of the cuvette were a 0.4 GBq 125I source and a scintillation crystal/photomultiplier tube assembly. This assembly was connected to a single channel analyser (SCA)/scaler unit to count the transmitted photons through the cuvette. The scaler was interfaced to an IBM PC and counts accumulated in preset time intervals were transmitted to the computer via a serial interface. Experiments were performed to calibrate the unit for measurement of blood concentration of contrast agent (Isovue 300) and to determine the dispersion characteristics of the unit. Deconvolution was used to correct the measured concentration waveform for the dispersion introduced by passage through the lead in tubing and the cuvette. The precision of concentration measurements was determined to be between 5 and 10% using computer simulations and theoretical calculations. The method was used successfully in a number of patient and animal studies to measure the contrast concentration in blood following intravenous injection of contrast agent. PMID- 1409871 TI - Non-invasive techniques for the measurement of extraction fraction and permeability surface area product of 99Tcm DTPA in the human forearm. AB - Only a very limited number of clinical studies have been reported on the measurement of endothelial permeability to hydrophilic solutes (molecular weight less than 6000 Daltons) that normally gain free access to the extravascular space. Because of high extraction efficiencies into the extravascular space, the transfer rates of small solutes of molecular weight about 500 Daltons, like 99Tcm DTPA, are perfusion-dependent as well as diffusion-dependent. We describe non invasive techniques for measurement of clearance and extraction fraction of 99Tcm DTPA into the extravascular space of the resting forearm using a scintillation probe, from which we then calculated permeability surface area (PS) product. Our values for extraction fraction of about 0.5 and for PS product of about 3 ml per minute per 100 ml tissue are comparable to the values reported in the literature for resting skeletal muscle using more invasive techniques. PMID- 1409872 TI - Radiation dose reduction in diagnostic x-ray procedures. AB - The performance of K-edge filters to modify the x-ray spectrum is investigated experimentally in a variety of clinical situations involving bone/soft tissue imaging, with the aim of improving the optimization between image contrast and patient exposure. The results show that simultaneous improvement of contrast and reduction of exposure is possible for a wide range of patient sizes. For conditions of fixed contrast skin exposure reductions of better than 50% and integrated dose reductions of up to 30% have been achieved with tolerable increases in tube load. Rare earth salt solutions were used as an inexpensive alternative source of K-edge filtration, and their performance was found to be in no way inferior to that of expensive metal foils. PMID- 1409873 TI - A comparison of two breathing exercise programs for patients with quadriplegia. AB - This study compared the use of abdominal weights (AbWts) to inspiratory resistive muscle training (IMT) on selected measures of pulmonary function. Eleven patients, aged 16 to 41 years (mean = 27.8, SD = 8.3) with complete cervical injuries were randomly assigned to either an AbWts or IMT treatment group. Subjects in both treatment groups received daily treatments (five times weekly) for 7 weeks. Forced vital capacity (FVC), inspiratory capacity (IC), maximal voluntary ventilation (MVV), peak expiratory flow rate (PEFR), and inspiratory mouth pressure (PImax) were measured weekly. Analysis of variance for repeated measures showed no difference between the AbWts and IMT treatments; there were significant differences within each respective treatment group for all five variables. Although the data did not support the effectiveness of one method of training over the other, the larger increase in MVV with the IMT protocol may be indicative of an endurance training effect with this protocol. Future research should compare the effects of breathing exercise training to spontaneous recovery of the respiratory muscles in control subjects. PMID- 1409874 TI - Normal range of motion of the cervical spine: an initial goniometric study. AB - The purposes of this study were (1) to determine normal values for cervical active range of motion (AROM) obtained with a "cervical-range-of-motion" (CROM) instrument on healthy subjects whose ages spanned 9 decades, (2) to determine whether age and gender affect six cervical AROMs, and (3) to examine the intratester and intertester reliability of measurements obtained. Measurements were made on 337 subjects (171 females and 166 males) whose ages ranged from 11 to 97 years. Measurements were taken by five physical therapists with 7 to 30 years of clinical and teaching experience. Among male and female subjects of the same age, females had a greater AROM than did males for all AROMs except neck flexion. Among both males and females, each of the six cervical AROMs decreased significantly with age. From two pilot studies separate from the acquisition of the normal database, we determined our intratester and intertester reliabilities for making neck AROM measurements with the CROM instrument. We concluded that AROM measurements on the cervical spine with the CROM instrument demonstrated good intratester and intertester reliability, because the intraclass correlation coefficients were generally greater than .80. PMID- 1409875 TI - Use of an intensive task-oriented gait training program in a series of patients with acute cerebrovascular accidents. AB - The aims of this case report are to describe the application of an early and intensive task-oriented physical therapy program for gait relearning following stroke and to report the patients' ability to comply with the program. Ten patients, 60 to 75 years of age (mean = 69.8, SD = 7.3), with a middle cerebral artery infarct (confirmed by computerized tomography) were assigned to this special physical therapy program. Patients were treated twice a day, 5 days a week, from the eighth day after stroke for 5 consecutive weeks. To promote gait relearning, a program of early standing (using a tilt table when necessary), combined with weight-shifting exercises and feedback via a limb-load monitor as well as locomotor activities including exercises on a Kinetron and treadmill walking, was adapted for each patient's level of motor recovery. Walking on the treadmill (with a safety harness) was initiated as early as the second week after stroke in 4 patients, and all patients had started Kinetron training by the second week. Except for 1 patient, who was withdrawn from the study because of an infection, all patients showed good treatment compliance (93.6%) with the planned 50 treatments and were able to withstand a mean treatment duration of 44.8 minutes (SD = 6.3, range = 37.5-58.5), twice a day, during the first week of the program (8th to 14th day after stroke). Results from this pilot project indicate that intensive and graded locomotor activities can be very well tolerated in the early period after stroke. PMID- 1409876 TI - The effect of postural drainage positioning on ventilation homogeneity in healthy subjects. AB - Body position is known to have significant effects on oxygen transport. These effects, however, are seldom considered during postural drainage (PD). The purpose of this study was to examine the effect of modified PD positions on ventilation homogeneity (the evenness of the distribution of ventilation), which is a key component of oxygen transport. The single-breath nitrogen washout test was used to obtain an index of ventilation homogeneity (slope of phase 3 [SBN2/L%]). Seventeen healthy individuals, ranging from 22 to 40 years of age ( mean = 28.4, SD = 5.6), performed the single-breath nitrogen test while sitting, lying supine with the bed tipped head down, right side lying, and right side lying with the bed tipped head down. Within-subject one-way analyses of variance and Tukey's post hoc analyses were used to compare differences in SBN2/L% across the four positions. The distribution of ventilation was significantly less homogeneous in the side-lying positions compared with the supine and sitting positions. Although these results reflect a position-induced change in pleural pressure gradient, they also reflect the effect of gravity-independent, intraregional changes on ventilation distribution. Thus, modified PD positioning has a significant effect on ventilation homogeneity, which may predispose a patient to arterial desaturation. Given the complexity of the factors involved, patients considered for PD positioning should be monitored for arterial saturation. PMID- 1409877 TI - Effect of variation in the burst and carrier frequency modes of neuromuscular electrical stimulation on pain perception of healthy subjects. AB - The purpose of this study was to explore the effect of various combinations of burst and carrier frequencies of neuromuscular electrical stimulation (NMES) on subjects' perception of pain intensity associated with induction of high intensity muscle contractions. Twenty-seven healthy volunteers completed the study. After the initial test session, all subjects were treated in three additional sessions with nine combinations of burst frequencies (50, 70, and 90 bursts per second [bps]) and carrier frequencies (2,500, 5,000, and 10,000 Hz) at an NMES amplitude that produced torque equivalent to 50% of maximal voluntary contraction of their quadriceps femoris muscle. Subjects rated each frequency combination for perceived pain intensity with a visual analog scale. The combinations of burst frequencies (50, 70, and 90 bps) and carrier frequencies (2,500 and 5,000 Hz) do not differ from each other in perceived pain intensity but do differ significantly in perceived pain from the combinations of burst frequencies at the carrier frequency of 10,000 Hz. Thus, the clinician may have to try different stimulus combinations on patients at different current training levels to obtain the least individually perceived pain. PMID- 1409878 TI - Reliability of ground reaction force measurements during dynamic transitions from bipedal to single-limb stance in healthy adults. AB - The consistency of ground reaction force (GRF) variables underlying dynamic transitions from bipedal to single-limb stance during a single-leg flexion movement was examined in 18 healthy adult subjects aged 21 to 47 years (mean = 31.1, SD = 8.6). Force platforms were used to measure the GRFs during fast and natural speeds of movement. Separate intraclass correlation coefficients (ICCs) were calculated for three temporal variables (ie, onset of the propulsive and braking phases of the lateral horizontal GRF component and time to unload the flexing limb) and for two magnitude variables (ie, propulsive impulse [PROP] and braking impulse [BRAK]). The ICCs for both PROP and BRAK were > or = .73 for fast movements and > or = .88 at the natural speed. The ICCs for the temporal variables were > or = .66 at fast speeds and > or = .37 at the natural speed. We concluded that measurements of PROP and BRAK are reliable across a range of speeds during transitions in stance support and that these variables may be tightly regulated by the movement control system. Temporal variables, particularly at the natural speed, exhibited lower reliability estimates, suggesting that measurements of these events have greater variability. Reliability of measurements of GRF variables provides useful information for the clinician regarding underlying control processes governing dynamic transitions in stance support. PMID- 1409879 TI - The twenty-sixth Mary McMillan Lecture. PMID- 1409880 TI - Who owns an idea? PMID- 1409881 TI - The efficacy of laser therapy for musculoskeletal and skin disorders: a criteria based meta-analysis of randomized clinical trials. AB - The efficacy of laser therapy for musculoskeletal and skin disorders has been assessed on the basis of the results of 36 randomized clinical trials (RCTs) involving 1,704 patients. For this purpose, a criteria-based meta-analysis that took into account the methodological quality of the individual trials was used. The studies with a positive outcome were generally of a better quality than the studies with a negative outcome. No clear relationship could be demonstrated between the laser dosage applied and the efficacy of laser therapy, or between the dosage and the methodological score. In general, the methodological quality of these studies appeared to be rather low. Consequently, no definite conclusions can be drawn about the efficacy of laser therapy for skin disorders. The efficacy of laser therapy for musculoskeletal disorders seems, on average, to be larger than the efficacy of a placebo treatment. More specifically, for rheumatoid arthritis, posttraumatic joint disorders, and myofascial pain, laser therapy seems to have a substantial specific therapeutic effect. Further RCTs, avoiding the most prevalent methodological errors, are needed in order to enable the benefits of laser therapy to be more precisely and validly evaluated. PMID- 1409882 TI - Obtaining reliable measurements of knee extensor torque produced during maximal voluntary contractions: an experimental investigation. AB - The purpose of this study was to develop and test a protocol that could be used to obtain reliable measurements of knee extensor torque produced during maximal voluntary contractions. On each of 3 days, 10 subjects performed six consecutive maximal voluntary contractions, in the same randomized order, for each of the following 10 conditions: concentric isokinetic contractions at velocities of 30 degrees, 90 degrees, 120 degrees, and 180 degrees/s; eccentric isokinetic contractions at velocities of 30 degrees, 90 degrees, 120 degrees, and 180 degrees/s; and isometric contractions at 40 and 60 degrees of knee flexion. The peak torques produced were examined to determine on which day and during which contraction subjects produced the greatest torques for each condition. This information was used to develop a practice protocol. Fifteen different subjects were tested following this protocol. Subjects participated in two practice sessions, a test session, and a retest session. Intraclass correlation coefficients (ICCs) were calculated to determine the degree of agreement between torques for the test and retest sessions. The ICCs ranged from .87 to .98. The protocol developed appears to be useful for obtaining reliable measurements of knee extensor torque. PMID- 1409883 TI - Trunk kinematics during locomotor activities. AB - We investigated upper-body (ie, trunk) angular kinematics (motions) during gait, stair climbing and descending, and rising from a chair in two reference frames- relative to the pelvis and to room coordinates. Bilateral kinematic data were collected from 11 healthy subjects (6 female, 5 male), who were 27 to 88 years of age (mean = 58.9, SD = 17.9). During stair climbing, maximum trunk flexion relative to the room was at least double that during stair descending and gait. Arising from a chair required the most trunk flexion/extension range of motion (ROM) but the least abduction/adduction and medial/lateral (internal/external) rotation. Trunk ROM during gait was small (mean less than or equal to 12 degrees) and consistent with previous literature. Trunk range of motion relative to the room during stair climbing and descending was greater than trunk ROM during gait in all planes. The pelvis and trunk rotate in the transverse plane in greater synchrony during stair descending (mean = 8.1 degrees, SD = 5.6 degrees) than during gait (mean = 12.0 degrees, SD = 4.2 degrees). For all activities, trunk frontal and sagittal ROM relative to the pelvis was greater than that relative to the room coordinates. This finding suggests that trunk/pelvis coordination may be used to reduce potentially destabilizing anti-gravity trunk motions during daily activities. We conclude that upper-body kinematics relative to both pelvis and gravity during daily activities are important to locomotor control and should be considered in future studies of patients with locomotor disabilities. PMID- 1409884 TI - The effect of awareness of measurement error on physical therapists' confidence in their decisions. AB - This study examined whether physical therapists understand the meaning of measurement error and whether information about measurement error affects their decisions. One of four versions of two physical therapy problems was mailed to 500 randomly selected physical therapists. Therapists were asked to define reliability and error of measurement, to estimate the error of measurement of two assessments, and to make decisions about an intervention based on specific measurements. They were also asked to rate their confidence in those decisions. Problems varied on the presence or absence of measurement information and on the difference between an observed measurement and a criterion measurement against which the observed measurement must be compared to make a decision. The response rate was 62%; respondents represented a typical profile of practicing physical therapists. The therapists understood reliability, but they did not correctly describe the relationship between reliability and error of measurement. Their estimates of the error of measurement of the two assessments were reasonable for only one procedure. The presence or absence of measurement information and difference between observed and criterion measurements affected their confidence, albeit inappropriately, in only one problem. Confidence was not affected by the therapists' level of experience, type of reading, formal study, or degree earned. Therapists responded to the two problems differently. The problems involved different measures, roles, utilities, and structures. The process of decision making does not generalize to all decision types. Measurement principles and strategies of use in decision making must be emphasized in physical therapy curricula so that physical therapists can consider the quality of their assessment data in making clinical decisions. PMID- 1409885 TI - Cardiorespiratory responses of healthy subjects to calisthenics performed on land versus in water. AB - This study evaluated the oxygen consumption (VO2) and heart rate response curves for standardized upper- and lower-extremity exercise on land and in water. Forty healthy subjects performed one upper-extremity and one lower-extremity exercise at three selected cadences on land and in water. Steady-state heart rate was determined by electrocardiographic radiotelemetry and expressed as a percentage of age-predicted maximal heart rate (% APMHR). Percentage of age-predicted maximal heart rate was used as the criterion measure of relative exercise intensity. Oxygen consumption was determined by the open-circuit method. Results indicated systematic increases in VO2 from 2 to 9 metabolic equivalents (METs) (1 MET = 3.5 mL O2.kg-1.min-1) and % APMHR from 45% to 73% with increased cadence. The VO2 responses were highest during water exercise, whereas % APMHR was greater during land exercise. Based on the magnitude of the responses, water calisthenics appear to be of sufficient intensity to elicit training adaptations. Training studies are needed to document these changes. PMID- 1409886 TI - Chronic dermal ulcer healing enhanced with monophasic pulsed electrical stimulation. PMID- 1409887 TI - Effectiveness of manual and mechanical techniques. PMID- 1409888 TI - Quantum yields and kinetics of the photobleaching of hematoporphyrin, Photofrin II, tetra(4-sulfonatophenyl)-porphine and uroporphyrin. AB - Porphyrins used as sensitizers for the photodynamic therapy (PDT) of tumors are progressively destroyed (photobleached) during illumination. If the porphyrin bleaches too rapidly, tumor destruction will not be complete. However, with appropriate sensitizer dosages and bleaching rates, irreversible photodynamic injury to the normal tissues surrounding the tumor, which retain less sensitizer, may be significantly decreased. This paper surveys the quantum yields and kinetics of the photobleaching of four porphyrins: hematoporphyrin (HP), Photofrin II (PF II), tetra(4-sulfonatophenyl)porphine (TSPP) and uroporphyrin I (URO). The initial quantum yields of photobleaching, as measured in pH 7.4 phosphate buffer in air, were: 4.7 x 10(-5), 5.4 x 10(-5), 9.8 x 10(-6), and 2.8 x 10(-5) for HP, PF II, TSPP and URO respectively; thus, the rates of photobleaching are rather slow. Low oxygen concentration (2 microM) significantly reduced the photobleaching yields. However, D2O increased the yields only slightly, and the singlet oxygen quencher, azide, had no effect, even at 0.1 M. Photosensitizing porphyrins in body fluids, cells and tissues may be closely associated with various photooxidizable molecules and electron acceptors and donors. Therefore, selected model compounds in these categories were examined for their effects on porphyrin photobleaching. A number inhibited and/or accelerated photobleaching, depending on the compound, the porphyrin and the reaction conditions. For example, 1.0 mM furfuryl alcohol increased the photobleaching yields of HP and URO more than 5-fold, with little effect on PF II or TSPP. In contrast, the electron acceptor, methyl viologen, increased the photobleaching yield of TSPP more than 10-fold, with little accelerating effect on the other porphyrins. These results suggest that the mechanism(s) of the photobleaching of porphyrin photosensitizers in cells and tissues during PDT may be complex. PMID- 1409889 TI - The photochemistry of 5-methylcytosine and 5-methyl-2'-deoxycytidine in aqueous solution. AB - The nucleobase 5-methylcytosine (I) is a minor component of eukaryotic DNA thought to be important in regulation of gene expression. The photochemical reactions of this nucleobase and its 2'-deoxyribonucleoside, 5-methyl-2' deoxycytidine (II), in water have been studied. These reactions lead, respectively, to 3-amino-2-methylacrylamidine (Ib) and 3-(2-erythro-D pentopyranos-1-yl)amino-2-methylacrylamidine (IIb) as the main photoproducts. The structure of the photoproducts was established by spectroscopic methods (1H and 13C NMR, UV spectroscopy, electron impact and liquid secondary ion mass spectrometry); in the case of Ib, confirmatory evidence was obtained by chemical methods (photolysis of 5-methyl[2-13C]cytosine, hydrolysis of N-carbomethoxy-3 amino-2-methylacrylamidine and reaction of Ib with 1,1'-carbonyldiimidazole to give I). The quantum yield for formation of Ib was determined to be 1.8 x 10(-3) at pH 7.5 while the quantum yield for formation of IIb has a lower value of 0.2 x 10(-3) at pH 7.5. These quantum yields depend strongly on pH and reach maximum values of 2.0 x 10(-3) at pH 7.0 (Ib) and 0.6 x 10(-3) at pH 5.0 (IIb). The mechanism of formation of Ib (or IIb) is proposed to involve nucleophilic attack of water on the C-2 position of photoexcited I (or II), followed by ring opening and decarboxylation of an intermediate carbamic acid. PMID- 1409890 TI - Oxygen dependence of hypericin-induced phototoxicity to EMT6 mouse mammary carcinoma cells. AB - The photodynamic effect of hypericin on EMT6 mouse mammary carcinoma cells was investigated in vitro under aerobic and hypoxic conditions. Under aerobic conditions, hypericin-induced photocytotoxicity was dose dependent within a 1-50 microM range. Under hypoxic conditions, cells were resistant to hypericin-induced phototoxicity. In the dark, no cytotoxicity was observed at any hypericin concentration tested either aerobically or hypoxically. Cellular accumulation of hypericin, examined by chemical extraction and spectroscopy, occurred under both hypoxic and aerobic conditions. Fluorescence photomicrographs of cells exposed to hypericin corroborate drug uptake in the plasma membrane and subcellular regions. Our results demonstrate that hypericin cytotoxicity to EMT6 mouse mammary carcinoma cells in vitro is both light and oxygen-dependent. These results suggest that EMT6 cell kill caused by photoactivated hypericin is mediated by an oxygen-dependent mechanism, rather than by a type I oxygen-independent mechanism. PMID- 1409892 TI - Inhibition of phototaxis in Volvox aureus by natural and simulated solar ultraviolet light. AB - Exposure to artificial UV wavelengths and the UV component of sunlight delays positive phototaxis in the green alga Volvox aureus. Broad band wavelength filters were used to modify the output from UV-B sources (280-320 nm) and natural sunlight. The delay in phototaxis by artificial UV is increased with exposure to shorter UV-B wavelengths. Natural sunlight experiments were performed with exposure to full sunlight and to its UV component only. The UV component present in summer sunlight produced long periods of inhibition in phototaxis and even lethality, while exposure to the total spectrum of sunlight had no significant effects on movement or survival. The data indicate that although this species of alga is well equipped to deal with present levels of UV exposure, increases in the short UV-B wavelengths in sunlight may force an alteration in patterns of photomovement. PMID- 1409891 TI - DNA associated with the cell membrane is involved in the inhibition of the skin rejection response induced by infusions of photodamaged alloreactive cells that mediate rejection of skin allograft. AB - Cell membrane DNA (cmDNA) is a form of DNA located on the surface of human and murine T-cells. It has recently been characterized as a target for photomodification by 8-methoxypsoralen (8-MOP) and long-wave ultraviolet light (UV-A). Whereas 8-MOP itself is biologically inert, photoactivated 8-MOP is covalently bound to pyrimidine bases in DNA. We have investigated the possible involvement of cmDNA photomodification in the induction of the suppression of skin allograft rejection in BALB/c mice preimmunized with 8-MOP/UV-A photodamaged alloreactive cells which mediates this allograft rejection. This suppression is demonstrated by inhibition of delayed-type hypersensitivity (DTH) and mixed leukocyte culture (MLC) responses. Splenocytes from BALB/c mice undergoing rejection of CBA/j skin graft which contained an expanded population of the effector T lymphocytes that mediate the rejection were treated with DNAse to remove cmDNA before or after treatment with 8-MOP and UV-A prior to infusion into naive BALB/c recipients. Mice that received pretreated effector cells were tested for MLC responses to CBA/j or B10 alloantigens before and after the DTH response. The DTH response of all groups of pretreated BALB/c mice to the relevant alloantigen was specifically suppressed as compared with the response of control mice. However, adoptive transfer of the suppression of the DTH response was optimally demonstrable only in syngeneic recipients of cells from donor mice treated with photodamaged alloreactive cells. Also, splenocytes from BALB/c mice immunized with photodamaged alloreactive cells demonstrated highly significant hyporesponsiveness and suppression of the MLC response of naive mice to the relevant alloantigen in the case of the primary MLC response, and to both alloantigens in the secondary MLC response which was totally eliminated by prior pretreatment of these effector cells with DNAse. Therefore, it appears that the suppression of the DTH response can be induced by pretreatment of the effector cells with DNAse and/or 8-MOP and UV-A but is adoptively transferable optimally only from mice which are recipients of photodamaged alloreactive cells. Moreover, the effectiveness of this treatment is decreased by prior removal of cmDNA from these cells. The presence of cmDNA is necessary for induction of suppression of the primary and secondary MLC responses in mice treated with photodamaged cells of allograft rejection. PMID- 1409893 TI - Chlorofluorocarbons and ozone. PMID- 1409894 TI - Photochemotherapy of cancer: experimental research. PMID- 1409895 TI - 1992 Ray G. Daggs Award. PMID- 1409896 TI - Russian thermophysiology today. PMID- 1409897 TI - Integrative biology of exercise. APS conference. Colorado Springs, Colorado, September 23-26, 1992. Abstracts. PMID- 1409898 TI - RO1s: an endangered species? PMID- 1409899 TI - Opioid mediation of the antiaversive and hyperalgesic actions of bradykinin injected into the dorsal periaqueductal gray of the rat. AB - Reported evidence indicates that the dorsal region of the periaqueductal gray matter (PAG) is involved in the modulation of both pain and aversion, and that opioid mechanisms, among others, participate in their modulation. Since many central actions of bradykinin (BK) have been shown to be similar to those of morphine, the present was undertaken to measure the effects of microinjection of BK into the PAG on the thresholds of aversive electrical stimulation of the same brain area and of dental pulp electrical stimulation. Bradykinin, injected into the dorsal PAG, induced a dose-dependent increase in the aversive threshold, an effect similar to that reported by others for morphine. Also, as reported for morphine, the antiaversive effect of BK was antagonized by naloxone injected intraperitoneally. Whereas subcutaneously administered morphine induced marked analgesia, intra-PAG administration of BK caused a small but significant hyperalgesia. Similarly, morphine injected into the dorsal PAG tended to cause hyperalgesia instead of analgesia. Furthermore, the hyperalgesic effect of BK also appears to involve opioid mechanisms since it was blocked by naloxone. As in previously reported studies, intracerebroventricularly injected BK raised the pain threshold. These results indicate that BK mobilizes opioid mechanisms in the dorsal PAG that inhibit aversion but not pain. PMID- 1409900 TI - Wrist activity in a woman: daily, weekly, menstrual, lunar, annual cycles? AB - Wrist activity was monitored continuously for one year in a woman who went about her normal life. The year of data were analyzed for changes and rhythms--daily, weekly, menstrual, lunar, annual. For each day, average motions/5 minutes, activity onset, activity offset, alpha (duration of activity), and acrophase were measured. Periodograms and average daily wave forms were calculated. Well defined, entrained, daily rest-activity cycles were observed throughout the year with periods close to 24 hours. There was weekend delay (0.7 hours) in onset, weekend decrease in alpha (1.0 hours), and weekend advance of acrophase (0.4 hours). Motions/5 minutes decreased 9%, onsets were 0.3 hours later, and alphas were 0.4 hours shorter on menstrual cycle days 8 through 18 which should have encompassed the time of ovulation. Lunar phase had no effect. Annual changes in onset (1.1 hours), offset (1.2 hours), and acrophase (1.1 hours) were attributed to the 1-hour change between standard and daylight savings time. PMID- 1409901 TI - Event-related potentials in professional city drivers: heightened sensitivity to cognitively relevant visual signals. AB - Event-related potentials to visual stimuli were recorded in 24 healthy, young subjects: 15 professional Belgrade city drivers and nine nondriver controls (no amateur driving experience) during a tacitly neutral GO:NOGO CNV paradigm and during one which explicitly mimicked heavy traffic conditions. In both paradigms GO S1 was a 30 ms red light, NOGO S1 a green light of equal duration; S2 was, in both cases, a yellow light presented 1.5 s post-S1. Overall, the early and late CNV for GO conditions were significantly larger (more negative) than for NOGO. This GO:NOGO difference was accentuated in drivers, as seen by a significant group-condition interaction using analysis of variance. The mean late CNV was significantly greater in drivers compared to controls: for GO at Cz during the neutral paradigm -12.9 vs. -5.0 microV, respectively, and for the traffic paradigm -14.4 vs. -6.0 microV. There were no significant differences in the CNV between the neutral and the traffic paradigms in either group. The pattern of CNV response seen in these professional Belgrade city drivers seems to suggest a heightened sensitivity to the cognitive significance of visual stimuli. To our knowledge, event-related potentials are applied here for the first time in professional drivers, a cohort known to have a high incidence of psychosomatic disorders, presumably related to the demands made upon them by their occupation. Further investigation using such objective electrophysiologic methods is clearly warranted in this high-risk group. PMID- 1409902 TI - The use of CXB recombinant inbred mice to detect quantitative trait loci in behavior. AB - Although recombinant inbred (RI) series of mice have been developed to identify and map single-gene characteristics, they can also be used to identify quantitative trait loci (QTL) that account for small amounts of variance in quantitative traits such as behavior. We applied an RI QTL approach to the analysis of published behavioral data from seven studies that used the CXB RI series of mice. Nearly all of the behaviors showed strain distribution patterns indicative of multiple-gene rather than single-gene influence. Although the CXB series is limited to seven RI strains, RI QTL association analysis suggests QTL candidate markers for several behaviors, including avoidance and exploration. PMID- 1409903 TI - Dissociation of multiple behavioral effects between olfactory bulbectomized C57Bl/6J and DBA/2J mice. AB - The behavioral effects of bulbectomy and subsequent antidepressant treatment in two mice strains were compared on measures of open field behavior and passive and active avoidance 2 and 4 weeks after surgery. After bulbectomy, both strains displayed elevated locomotion in open field, corrected by antidepressants. Enhanced rearing was decreased by antidepressants in C57Bl/6J, but not in DBA/2J mice. Passive avoidance, being intact 2 weeks after surgery in both strains, was strongly impaired 4 weeks after bulbectomy in C57Bl/6J mice, with antidepressants restoring the performance. Active avoidance acquisition and retention were also dramatically disturbed in C57Bl/6J mice 2 and 4 weeks after surgery, and antidepressants had recuperative effect. In contrast, bulbectomized DBA/2J mice didn't show any significant passive or active avoidance deficits, and antidepressant treatment seemed to have no effect on their learning ability. The observed strain differences suggest that bulbectomy may produce quite diverse neurophysiological and neurochemical alterations in two strains. PMID- 1409904 TI - Halothane anesthesia causes state-dependent retrieval failure in mice. AB - Effects of exposure to halothane on memory processing was studied using single trial inhibitory avoidance learning to measure retention. Mice were anesthetized with halothane either before training, immediately after training, or both before training and before testing. Results showed that memory was not impaired by posttraining halothane exposure, indicating that the anesthetic does not cause retrograde amnesia. Mice trained after recovery from halothane showed a robust memory loss 24 h later. This deficit could be alleviated by reexposure to the anesthetic before the retention test. Mice given multiple training trials following recovery from the anesthetic showed a normal rate of learning when compared with controls, but deficient retention. This indicates that the performance deficit was the result of impaired retention (anterograde amnesia) rather than disrupted acquisition. Anterograde amnesia occurred when training was delayed up to 2 h after recovery from anesthesia. These findings indicate that the memory impairment following halothane anesthesia is the result of a state dependent retrieval failure. PMID- 1409905 TI - Ingestive behavior and body temperature of pigeons during long-term cold exposure. AB - Pigeons well adapted to living in 21 degrees C ambient temperature (T(a)) were continuously exposed to cold T(a) for 6 days (Experiment 1) or 30 days (Experiment 2). The pigeons lived on a 12:12 L:D cycle where they could obtain short access to food and water at any time in the light phase by making 12 keypeck responses. Across the two experiments, the levels of cold exposure were 6 degrees C, 1 degrees C, and 0.6 degrees C. In cold, total daily food intake increased gradually across the first few days of the exposure, and the new level of food intake was inversely related to T(a). The daily ratio of total water drunk to total food eaten averaged approximately 1.3 in 21 degrees C, fell to approximately 1.0 on day 1 of cold exposure, and remained at that level for as long as 30 days. The day-night cycle in core body temperature was not changed by cold exposure. The bimodal temporal pattern of feeding in the light phase, which is characteristic of pigeons in moderate T(a), was preserved in the cold although the absolute level of feeding activity was enhanced. An analysis of the ways individual pigeons achieved total daily food intake by combining a number of feeding episodes with an average amount eaten per episode revealed considerable variation between birds, but a relatively constant feeding style within bird over time. In the colder temperatures used, however, the pigeons all increased the number of feeding episodes per day. The results provide the first detailed analysis of cold-induced changes in ingestive behavior in the pigeon and raise several questions about the behavioral expression of cold-sensitive regulatory processes. PMID- 1409906 TI - Prolonged ambulatory monitoring of colonic motor activity in the pig. AB - The aim of this study was to develop a chronic model suitable for repeated, long term studies of the interaction of behavior and colonic function in unrestrained pigs. Cecostomies were created in three 20-30 kg micropigs under general anesthesia. Fistulas were created by suturing the bowel to the abdominal wall. Recordings were made by passing a small (8F) solid-state pressure transducer through the fistula into the proximal bowel and connecting it to a battery operated data logger worn in a vest on the pig's back. Cecostomies have remained patent and trouble-free for over 18 months. No serious infections have occurred. Preliminary data from a total of thirteen 24-h recording sessions showed 54% of all contractile activity to be in the 2-4 cpm frequency range. Increased motility was seen following meals and upon morning awakening. Motility was minimal during the night. Infrequent (10.31 +/- 2.05/24 h; mean +/- SD) propagated contractions were also noted. These contractions were generally of low amplitude (33.24 +/- 3.81 mmHg). These techniques allow prolonged, intraluminal recordings to be made from the colon of the unrestrained pig. PMID- 1409907 TI - Plasma corticosterone response of rats with sociopsychological stress in the communication box. AB - The purpose of present study was to investigate the physiological characteristics of sociopsychological stress induced by the communication box method. In this method, the nonfoot shocked rats were used as the psychologically stressed experimental group. In acute stress experiments, nonfoot shocked rats were exposed to emotional responses from foot shocked rats for 6 h in the light (0900 1500) or in the dark phase (2100-0300). In the light phase, the induced increase in plasma corticosterone levels of nonfoot shocked and foot shocked rats returned to corresponding control levels 6 h following the initiation of stress session, whereas those in the dark phase were significantly higher. Although there were some differences in corticosterone responses between both phases, the acute effect of sociopsychological stress was unclear. Chronic stress experiment with daily exposure for 1 h to sociopsychological stress caused the plasma corticosterone levels of nonfoot shocked rats to increase significantly not only in the postexposure level (just after stress exposure) but also in the preexposure level (before stress exposure) when naive rats were used daily as foot shocked animals. These results suggest that the repeated exposure of sociopsychological stress can induce physiological changes, and stressful situation can be established with only emotional responses from foot shocked rats. PMID- 1409908 TI - Prior exposure to a running wheel and scheduled food attenuates polydipsia acquisition. AB - Groups of rats were given different histories before exposure to daily, 2-h fixed interval (FI) 1-min food-schedule sessions with water available. In a previous study, a group with a history of chronic exposure to FI 1-min sessions without water subsequently had a reduced rate of acquisition and final level of schedule induced polydipsia compared to a control group lacking this history. In the present study, groups with histories of chronic exposure to FI 1-min sessions and a concurrent running wheel were even more attenuated in their subsequent acquisition of polydipsia. Substitution of 5% ethanol for session water in the final phase produced a convergence in group intakes, except for a group which continued to have access to the running wheel. The ethanol intake of this group was relatively suppressed. PMID- 1409909 TI - Consummatory behaviors and weight regulation in pregnant, lactating, and pregnant lactating mice. AB - Pregnant Rockland-Swiss (R-S) albino mice consumed significantly more food and water and gained significantly more weight between gestation days 8-17 compared to virgin R-S females maintained in isolation for a comparable period. Postpartum (days 1-10) patterns of ingestion and weight change among thelectomized (nipple deprived) mouse dams provided with young did not differ significantly from those of virgin animals without young. Sham- and nonoperated dams received suckling stimulation from young and consumed about 100% more food than thelectomized or virgin females (Experiment 1). Pregnancy concurrent with lactation does not increase further the hyperphagic response of female mice. Nipple presence is the principle regulator of postpartum hyperphagia in lactating and simultaneously pregnant-lactating mouse dams (Experiment 2). PMID- 1409910 TI - Ontogeny of behavioral inhibition induced by unfamiliar adult male conspecifics in preweanling rats. AB - Previous studies showed that when socially isolated at 22 degrees C, postnatal day 14 rats, but not younger day 7 rats, reduce their emission of ultrasonic vocalizations when exposed to an unfamiliar adult male rat, a naturalistic threat. Because ultrasound production is associated with factors such as age and body temperature, this study examined in age-appropriate thermoneutral temperature ranges whether preweanling rats of different ages are equally capable of inhibiting their emission of ultrasounds when threatened. In Experiment 1, 7- and 14-day-old rats were socially isolated and exposed to unfamiliar anesthetized adult male rats in a thermoneutral environment. Only 14-day-old rats significantly reduced their emission of ultrasounds. This reduction in ultrasound production was accompanied by freezing. In Experiment 2, additional ages were examined under identical test conditions. At 3, 6, and 9 days of age, pups frequently emitted ultrasounds when exposed to the anesthetized male rat. However, at 12 days of age, rat pups responded to the anesthetized male rat by freezing and significantly reducing their emission of ultrasounds. Results indicate clearly that under the present testing conditions the ability of rat pups to inhibit ultrasounds and freeze when threatened is not present at birth but emerges by the end of the second postnatal week. PMID- 1409911 TI - Changes in Na concentration in cerebrospinal fluid during acute hypernatremia and their effect on drinking in juvenile rats. AB - To clarify if there are age-related differences in osmoreception, we measured changes in Na concentration in cerebrospinal fluid ([Na]csf) during and after acute hypernatremia in juvenile (JR) and adult rats (AR). The Na concentrations in plasma ([Na]pl) and [Na]csf were measured during intravenous infusion of 1 M NaCl solution (INF, 0.2 ml/100 g body wt. for 10 min) and for 20 min thereafter in anesthetized rats. To measure [Na]pl, a flow-through Na-sensitive electrode was placed in an extracorporeal shunt from a carotid artery to a jugular vein, and to measure [Na]csf, a Na-sensitive electrode was placed in the right lateral ventricle. There was a linear relationship between delta[Na]pl and delta[Na]csf during INF. The slope of delta[Na]pl vs. delta[Na]csf was 0.42 +/- 0.03 (n = 7) in JR, which was significantly higher (p less than 0.01) than in AR (0.23 +/- 0.04, n = 6). We also measured water intake during and after INF of the same amount of 1 M NaCl solution in conscious JR (n = 6) and AR (n = 6). The JR drank 1.93 +/- 0.22 ml/100 g body wt. of water within 30 min of the start of INF, which was significantly more (p less than 0.05) than AR drank (1.20 +/- 0.13 ml/100 g body wt.). These results indicate that the movement of Na or water, or both, between the blood and cerebrospinal fluid in acute hypernatremia is greater in JR, and that the osmoreceptors in JR are more sensitive than those in AR. PMID- 1409912 TI - Genotype-dependent involvement of limbic areas in spatial learning and postlesion recovery. AB - Male C57BL/6 (C57) and DBA/2 (DBA) mice with hippocampal, amygdaloid, or sham lesions were tested in a radial eight-arm maze 1 or 4 weeks after surgery. The results show that the effect of the lesions varied according to the performance level of the strain considered. In the high-learner C57 strain, the two lesions impaired acquisition at both postlesion intervals. Conversely, in the low-learner DBA strain, only hippocampal lesions impaired acquisition 1 week but not 4 weeks after lesioning. It is hypothesized that if more limbic areas are involved in controlling spatial learning in C57 mice, these structures could be processing distinct but complementary memory attributes, thus contributing to a high baseline performance. This, however, also entails an increased sensitivity of C57 performance to brain damage with reduced possibilities of long-term recovery. PMID- 1409913 TI - Naltrexone-sensitive analgesia following exposure of mice to 2450-MHz radiofrequency radiation. AB - To determine whether exposure to radiofrequency radiation (RFR) would induce sufficient thermal stress to activate endogenous opioid mechanisms, male Swiss Webster mice were exposed to 10, 15, and 20 mW/cm2 RFR in a 2450-MHz waveguide system for 10 min at specific absorption rates (SARs) of 23.7, 34.6, and 45.5 W/kg, respectively, then tested in the abdominal constriction paradigm. Confinement in the RFR exposure chamber alone did not appreciably alter body temperature but did appear to induce a stress-associated analgesia that was not blocked by naltrexone. Exposure of confined mice to RFR raised body temperature and further increased analgesia in an SAR-dependent manner. The high SAR-induced analgesia, but not the hyperthermia, was blocked by naltrexone. These findings suggest that 1) RFR produces SAR-dependent hyperthermia and analgesia, and 2) RFR induced analgesia is mediated by opioid mechanisms while confinement-induced analgesia involves nonopioid mechanisms. PMID- 1409914 TI - Effects of amphetamine on food intake and weight: timing of injections and food access. AB - Although the effects of amphetamine on food consumption and body weight in nondeprived animals are of interest for theoretical and clinical reasons, there are only a few studies on this topic in the literature. In Experiment 1, independent groups of nondeprived rats were given daily injections of 0, 1, 2, 5, or 10 mg/kg d-amphetamine sulfate shortly after light onset for 30 days. While drug treatment did not affect food consumption, all amphetamine-treated groups lost weight over the initial 12 days and then, over the final 18 days of treatment, gained weight at the same rate as controls. Experiment 2 assessed whether the effects of amphetamine on these measures are influenced by the timing of the daily injections relative to the light-dark cycle. As in Experiment 1, injections of amphetamine at light onset again produced weight loss while not affecting food consumption, whereas injections of the drug at light offset did not reliably affect either measure. Experiment 3 showed that the relationships among variables observed in nondeprived animals remain the same in animals restricted to 12 h of access to food each day and replicated the amphetamine induced hyperphasia observed earlier by Jones and Caul (9). PMID- 1409915 TI - Urine marking in male mice: responses to natural and synthetic chemosignals. AB - The effects of natural chemosignals and their synthetic terpenic analogs on urinary marking in mice were investigated. The number and size of marking spots, and percentage of response and avoidance/counter-marking behavior, were measured for dominant and subordinate males. The males' marking behavior was found to differ significantly based on the type of stimulus sample used. Marking behavior in response to female urine was significantly altered by addition of synthetic analogs (farnesene isomers) to it. Both dominant and subordinate males avoided marking the section of the test area soiled with stimulus samples containing either natural or synthetic farnesenes. Differential responses of the dominant and subordinate male mice were observed. PMID- 1409916 TI - Decreased NaCl sensitivity in zinc-deprived rats. AB - NaCl thresholds and ability to discriminate between NaCl and sucrose were assessed in rats using an operant discrimination conditioning procedure before and during moderate and severe zinc deprivation and during zinc supplementation. NaCl thresholds were approximately 1 mM before dietary zinc manipulation. They increased in all zinc-deprived rats tested 10 and 17 days after initiation of deprivation but did not change in pair-fed controls maintained on supplemental zinc. Threshold changes were greater for those rats severely zinc deprived than for those only moderately deprived and were greater as the period of deprivation lengthened. Plasma zinc concentrations decreased significantly in deprived rats from values obtained at baseline, values in severely deprived rats being significantly lower than in those only moderately deprived. Although zinc deprived rats discriminated NaCl from sucrose, they made more discrimination errors than controls. Following 24 days of zinc supplementation, previously deprived rats exhibited no significant improvement in gustatory performance, although their body weight increased and plasma zinc concentrations increased; but these later changes were not significant. These results demonstrate that zinc deprivation induces decreased gustatory sensitivity and confirm a role for zinc in taste. PMID- 1409917 TI - Is starch flavor unitary? Evidence from studies of cooked starch. AB - Although starch is the world's most abundant nutritive carbohydrate, its sensory properties are not as well understood as those of sugars. Previous researchers have assumed that all starches have the same flavor. The present experiments examined flavor differences among starches. Untrained rats were offered a choice of suspensions containing raw versus cooked starch. For some starches (potato and rice), rats strongly preferred cooked over uncooked starch. For other starches (regular corn, corn amylopectin, and wheat), rats showed little or no preference for cooked over uncooked starch. In order to determine whether the greater preference for cooked starch reflects a difference in flavor intensity, rats were conditioned to avoid potato or corn amylopectin starches by pairing ingestion of these substances with lithium chloride injections. Rats trained to avoid raw starch also avoided cooked starch, indicating that cooked and raw starch have similar flavors. However, when these trained rats were offered a choice between cooked and raw starch, they avoided the raw starch; this result is inconsistent with the assumption that cooking enhances the intensity of starch flavor. Similar results were obtained with corn amylopectin and potato starch, even though these starches differ greatly with regard to the effects of cooking on preference in untrained rats. However, rats trained to avoid potato starch avoided this starch to a greater degree than did rats trained to avoid corn amylopectin; conversely, rats trained to avoid corn amylopectin avoided this starch to a greater degree than did rats trained to avoid potato starch. Therefore, the flavor of starch is complex; there are specific flavor notes related to species and cooking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409918 TI - Consumption of salty food by rats: regulation of sodium intake? AB - The extent to which sodium levels may be regulated by consumption was examined in two experiments that offered rats foods varying in sodium chloride (NaCl) content. In the first, rats received single purified diets containing from 0% to 3% NaCl. There were no effects of NaCl level on the amount or pattern of daily food intake; water intake, however, increased with salt content. In the second study, rats had choices between a NaCl-free food and a food containing either 1, 2, or 3% NaCl for 1 week each. Total food intake was unaffected. Proportional intake of the salt-free option increased with the salt content of the alternate food, but not sufficiently to maintain a constant NaCl intake. After 8 weeks of exposure to a single food, intake of the salty option increased in the choice tests, but the level of NaCl (from 0.5 to 3.0%) in the exposure-phase food did not affect the subsequent choice. We conclude that when only one food is available, salt intake is governed by caloric requirements and sodium levels are regulated by excretion. When foods differing in NaCl content are available, consumption does contribute to the regulation of sodium balance, but the amount consumed is not tightly controlled. Rats' salt preference appears to increase with age or with experience eating the purified foods offered here, but experience eating salty food does not affect the preferred level of salt. PMID- 1409919 TI - Relationship between eye movements and oneiric behavior in cats. AB - The relation between oneiric behavior and rapid eye movements (REMs) in paradoxical sleep (PS) without muscle atonia was analyzed in cats. Most isolated REMs were related to orienting behavior, whereas most REM bursts were related to generalized body movements (jumping, attacking, etc.). Only isolated, high amplitude REMs had any possibility of corresponding to visual images in dreams. From these findings we propose the existence of both dream-related and nondream related REMs even in animals. PMID- 1409920 TI - Methyl xanthine, adenosine, and human taste responsivity. AB - The influences of three methyl xanthines (MX) on human taste responsivity, caffeine, theophylline, and theobromine, were examined using blind control procedures. Taste responsivity in the same subjects was determined using the matching procedure described by Schiffman (Study 1) and the whole-mouth procedure described by Sheperd (Study 2). In each study, the duration of MX pretreatment necessary to enhance taste responsivity was examined. No potentiation of overall- and taste-quality specific intensity ratings was observed for any tastant, independent of test procedure, type, and concentration of MX pretreatment, or length of MX pretreatment. Taste intensity ratings, especially for NaCl, were higher following pretreatment with water than methyl xanthine or adenosine combined with caffeine. Adenosine, added at several concentrations to caffeine pretreatments, influenced neither taste responsivity nor taste intensity ratings. PMID- 1409921 TI - Recognition of familiar individuals by touch. AB - I have examined whether adults can recognize their boyfriends/husbands or girlfriends/wives by stroking either their partner's hand or face. On both trials, subjects were asked to chose their mate from amongst two unfamiliar age- and gender-matched adult foils. During testing, the subject's eyes and nose were covered and auditory cues were masked by ambient noise. The results show that a significant proportion of the total sample succeeded on one or both of the touch recognition tasks. However, while both women and men were successful at the face touch-recognition task, only the women were successful at the hand-recognition task. I conclude that tactile cues afforded by stroking skin are sufficiently salient to allow for individual recognition. As for the gender-related difference, women may have an advantage at hand recognition because men's hands are more discriminable than women's hands. PMID- 1409922 TI - The mechanism and significance of pentagastrin-stimulated water intake in the pig. AB - The role of gastric secretion in drinking was investigated. Treatment of pigs with cimetidine (300 mg IV), which inhibits gastric secretion, did not change the level of feed or water intake, or alter the temporal relationship between eating and drinking. Gastric infusions of 0.15 M HCl (5 ml.kg-1.h-1) did not increase drinking. Pentagastrin infusion (0.05 microgram.kg-1.min-1) increased water intake in some, but not all pigs during a 1-hour infusion. Plasma protein levels increased significantly during 1-hour pentagastrin infusions (0.05 microgram.kg 1.min-1), indicating an estimated fall in blood volume of 2.5%. Captopril (1.75 mg/kg IV), which blocks the renin-angiotensin system, abolished pentagastrin stimulated drinking. It was concluded that gastric secretion does not play a direct role in normal, periprandial drinking but that in pigs the renin angiotensin system is involved in pentagastrin-stimulated drinking. PMID- 1409923 TI - Moderate exercise in young female S5B/P1 rats does not reduce body fat. AB - Weanling S5B/P1 female rats were divided into four groups as follows: high fat diet, exercised (FE); high fat diet, unexercised (FU); high carbohydrate diet, exercised (CE); and high carbohydrate diet, unexercised (CU). After 25 days of progressive training, exercised rats ran on a motor-driven treadmill for 30 days at 25 m/min per 1 h at 0 degree grade for 6 days a week. Rats were weighed weekly throughout the experiment and food intakes were recorded for the last 3 weeks of the experiment. After euthanasia at 15 weeks of age, three muscles, liver, heart, kidney, 3 fat depots, and tibia-fibula were dissected out and weighted. The carcass, including weighted organs and fat depots, was analyzed for body fat. Exercised rats, regardless of diet, weighed slightly but significantly more than unexercised rats. They also tended to eat more food and to have a higher quantity of fat-free body mass than unexercised rats. Percent body fat was similar for exercised and unexercised rats. The tibia weighed significantly more (p less than 0.05) in CU than in FU rats but the weight was similar in CE and FE rats. The density of the tibia was significantly higher (p less than 0.01) in exercised than in unexercised rats. PMID- 1409924 TI - Effect of chronic stress and exogenous glucocorticoids on regional fat distribution and metabolism. AB - It has been proposed that increased glucocorticoid hormones and decreased sex hormones affect regional fat metabolism and distribution. In the present work, it was hypothesized that chronic, uncontrollable stress, known to affect the pituitary-adrenal and pituitary-gonadal axes might, therefore, lead to differences in regional fat accumulation. In comparison with controls, male Sprague-Dawley rats stressed for 28 days, had significantly larger adipocytes. In addition, a tendency for a heavier fat pad and an increased lipoprotein lipase activity in the mesenteric depot was suggested. No significant changes were seen in epididymal, retroperitoneal, and inguinal regions. In order to study if the effects observed could be attributed to increased glucocorticoids, the response to a direct administration of supraphysiological doses of corticosterone, given either in the drinking water or via subcutaneous implantation of corticosterone pellets, was studied. Increased fat accumulation was shown in all fat depots in a dose-response fashion, but was significantly more pronounced in the mesenteric region. It was concluded that mesenteric fat tissue may respond to stress in a different manner from other fat depots. Glucocorticoids seem to be partly, but not solely, responsible for the changes observed in adipose tissue metabolism and distribution following exposure to uncontrollable stress. PMID- 1409925 TI - The comparative effects of abrupt vs. stepwise discontinuation of TPN in rats. AB - The comparative effects of discontinuing total parenteral nutrition (TPN: caloric ratio of glucose:fat:amino acid = 50:30:20) abruptly or in a stepwise manner on spontaneous food intake were investigated in two studies. Study 1: In 16 rats, TPN was given for 4 days, then stopped abruptly in eight rats. In the other eight rats, TPN was tapered; they received TPN at 75%, 50%, and 25% of their mean daily energy requirements per day for 3 consecutive days, and then switched to normal saline. Total parenteral nutrition induced a significant 60% reduction in spontaneous food intake (SFI) in both groups during the first TPN day. After 4 days of TPN, an 80% decrease in SFI had occurred in both groups. Resumption of SFI was significantly sooner in the abruptly-stopping group than in the stepwise stopping group. But, in the latter group, there was a significantly greater cumulative caloric intake during the entire study. Study 2: In 32 rats, TPN providing either 100%, 50%, or 25% of their mean daily caloric requirements was given to three groups each of eight rats, for 3 days, then abruptly changed to normal saline; control rats received normal saline throughout. The TPN-induced decrease in SFI was proportional to the caloric density of the solution infused. Three days of 100%, 50%, or 25% TPN infusion led to an approximate 85%, 60%, or 35% decrease in SFI, respectively. Spontaneous food intake recovery was independent of the caloric density of TPN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409926 TI - Dynamics of oral intake resumption after general anesthesia and operation in rats. AB - The influence of general anesthesia and operation on dynamics of postoperative food intake resumption was investigated in eight rats. A laparotomy was performed on each rat under anesthesia induced by intraperitoneally injected chloral hydrate. Spontaneous food intake and feeding indexes were continuously measured using an Automated Computerized Rat Eater Meter (ACREM) before and after operation. Although spontaneous food intake and all feeding indexes were depressed immediately following anesthesia and operation, each feeding index was depressed to a greater degree during the dark vs. the light cycle. Initially, rats fully capable of eating ate fewer, smaller, and shorter meals. The return to normal of each feeding index differed temporally. Thus, although meal number normalized by the third postoperative day, meal size by the sixth postoperative day, and meal duration by the fourth postoperative day, normalization of meal number during the light cycle occurred sooner than during the dark cycle, while the converse occurred with meal size and meal duration. PMID- 1409927 TI - Social modulation of behavioral reproductive senescence in female rats. AB - During aging, the lordosis reflex of female rats changes from a state of cyclic lordosis, when the lordosis reflex can be elicited by manual palpation only on proestrus, to a state of constant lordosis (CL), when it can be elicited daily. Social signals from other females altered this pattern of behavioral senescence. Group living decreased the lordosis reflex intensity in both old and young rats and delayed the onset of CL. Long-term group living delayed CL until late in the life span, while temporary group living delayed it only until rats returned to isolation. Long-term group living also changed the temporal relationship between CL and the acyclic, anovulatory state of estrus. Finally, the lordosis reflex intensity, measured by manual palpation, predicted the old rats' receptivity to a male, indicating that constant lordosis is a biomarker for other aspects of behavioral reproductive senescence. PMID- 1409928 TI - Sleep deficits in rats after NMDA receptor blockade. AB - N-Methyl-D-aspartate (NMDA) receptor blockade disrupts a variety of functions associated with neural plasticity, including acquisition of learned responses and long-term potentiation. Deficits in memory are significantly correlated with deficits in measures of paradoxical sleep in several amnesic populations. The present experiment therefore assessed whether NPC 12626, a competitive NMDA receptor antagonist, also disrupts sleep. NPC 12626 (1, 10, 50, and 100 mg/kg) or saline was administered to Sprague-Dawley rats 30 min prior to 3-h daytime recording periods. Paradoxical sleep was selectively impaired at all but the highest dose, which prevented all sleep during the recording period. Some deficits in nonparadoxical sleep first appeared at the 10 mg/kg dose but did not became prominent until the 50 mg/kg dose. The results thus show that NPC 12626 impairs sleep states in rats and demonstrate that paradoxical sleep is particularly susceptible to the effects of NMDA receptor blockade. These findings, along with previous evidence that NMDA antagonists impair waking measures of arousal, provide evidence that all sleep-wake states are impaired by NMDA receptor blockade. More generally, the results suggest that some brain mechanisms underlying sleep and memory may share common elements. PMID- 1409929 TI - Estrogen in peripheral plasma during postnatal development in gray short-tailed opossums. AB - Plasma samples obtained from gray short-tailed opossums (Monodelphis domestica) at selected ages through adulthood were assayed for estrogen (E). Levels of E in one mixed-sex plasma pool of animals aged postnatal day (pd) 4 and one of two mixed-sex plasma pools of animals aged pd 8 were over 300 pg/ml. On pd 16, E levels in males and females averaged 30 and 47 pg/ml, respectively. While no significant sex differences in E levels were seen on pd 30 or pd 60, mean E levels for animals on pd 30 were significantly higher (275 pg/ml in males and 181 pg/ml in females) than on pd 60 (78 pg/ml in males and 85 pg/ml in females) or pd 145 (adults). In adult animals, estrogen levels in females averaged 54 pg/ml; all adult male E levels were below the limit of sensitivity of the assay. Maternal E levels, which did not vary significantly by age of litter, averaged 10 pg/ml overall. These findings are discussed with respect to possible significance of high E levels in developing marsupials for sexual differentiation and general brain development. PMID- 1409930 TI - Assessing odor generalization in the rat: a sensitive technique. AB - In investigating the ability of the rat to discriminate among urine odors from mice of different genetic strains, we developed a technique for determining the extent of odor generalization. Trained rats performed a discrete trial, go/no-go procedure, touching a bar in the presence of an S+ odor for water reward. Rats easily learned this task and restricted their responding to trials with the S+ stimulus, even though there was no penalty for responding to S-. However, when presented with test stimuli that might be more similar to S+ or S-, some rats responded only to the S+, and not at all to S- or any generalization stimuli. We then created series of stimuli composed of different levels of adulteration of the S+ stimulus with generalization stimuli. With these stimuli, rats produced graded levels of responding, allowing comparisons of similarity among odorant stimuli. This technique can be applied to other types of odorant stimuli, particularly biological compounds of unknown concentration or purity, and should be of use in an operant laboratory studying odorant perception, or odorant characteristics. PMID- 1409931 TI - Pineal melatonin and locomotor activity of rats under gradual illuminance transitions. AB - The locomotor activity and pineal melatonin patterns of adult male rats were compared under two different lighting regimes. The animals were kept 8 days under 12/12 h light/dark cycles with abrupt or slowly decreasing and increasing transitions (twilight periods about 2 h). The onsets of high activity and melatonin rise were phase-locked in the two conditions and related to about half maximal illuminance level of the gradual dusk. The high activity of the control rats stopped 30-60 min before the abrupt light onset and the rats under the gradual lighting transitions ceased the locomotor activity at about 1 hour before the half-maximal illuminance. The melatonin peak levels were found 4 h before the abrupt lights-on time. Under the slow illuminance transitions the average melatonin peak was related to the illuminance level between maximum and minimum in the morning. Thus, both the melatonin rhythm and the rest-activity rhythm under the gradual dawn and dusk were adjusted according to about half-maximal illuminances in the present conditions. PMID- 1409932 TI - Testosterone as appetitive and discriminative stimulus in rats: sex- and dose dependent effects. AB - Stimulus properties of subcutaneously injected testosterone were studied in male and female rats. In a conditioned place preference procedure, dose-dependent effects (doses: 0, 0.5, and 1 mg/kg) were observed in males. In females, no place preference could be established (doses: 0, 1, and 3 mg/kg). In addition, 1 mg/kg testosterone acquired discriminative stimulus control in male rats in a taste aversion procedure. Animals injected with this hormone prior to saccharin-LiCl pairings and with its vehicle prior to saccharin-NaCl pairings suppressed fluid intake following the administration of testosterone and not following the administration of the vehicle. Subsequent generalization tests revealed dose dependent stimulus control of this hormone (range of substitution doses: 0.125-2 mg/kg). It is concluded from the results that at least pharmacological (supraphysiological) doses of testosterone may act as appetitive stimuli in male rats, but not in female rats. Furthermore, in male rats (pharmacological doses of) testosterone also possess discriminative stimulus properties. PMID- 1409933 TI - Olfactory bulb removal affects partner preference development and estrus induction in female prairie voles. AB - In female prairie voles (Microtus ochrogaster) bilateral olfactory bulbectomy reduced affiliative behavior, as measured by social contact, and prevented the formation of partner preferences. Unilateral olfactory bulb removal did not significantly influence affiliative behavior, but did inhibit partner preferences. Bilateral, but not unilateral, bulbectomy significantly reduced the proportion of females exhibiting behavioral estrus following male exposure. In contrast to affiliative and sexual behavior, parental behavior was not significantly affected by either bilateral or unilateral olfactory bulbectomy. These results suggest that divergent sensory-neural pathways underlie social, sexual, and parental behaviors in this species. PMID- 1409934 TI - Abstinence from smoking decreases habituation to food cues. AB - Smokers typically gain weight after cessation due, in part, to increased caloric intake. This increase may be due to enhanced responding to sensory characteristics of foods resulting from a failure to habituate to food cues. To test this possibility, salivation to eight presentations of strawberry yogurt was assessed in male smokers and nonsmokers in two sessions. To test stimulus specificity, on the ninth trial, subjects were presented either more strawberry yogurt or lemon yogurt. Smokers were studied under nonabstinent or abstinent conditions. Salivation for nonabstinent smokers and nonsmokers decreased over presentations, while abstinent smokers showed little change. Nonabstinent smokers and nonsmokers recovered salivation when the new flavor yogurt was presented, and showed greater consumption on the final trial for the different versus same flavor yogurt. Nonabstinent smokers participated in additional within-session smoking sessions to control for withdrawal. Nonabstinent subjects were not different across smoking or not smoking sessions, suggesting the effects are not due to the acute effects of withdrawal. PMID- 1409935 TI - Natriuresis after a water load in humans under different sodium body content. AB - The present study was aimed at observing the diuretic and natriuretic responses after a water load (2% body weight) in four groups of young consenting volunteers submitted previously, during three days, to a hypersodic (500 mEq Na/day), hyposodic (35 mEq Na/day), and normosodic (200 mEq Na/day) diet, or treated with furosemide (Lasix, 40 mg/day). During the treatment urine was collected each day. On the fourth day, in the morning, the bladder was emptied, the water load was ingested, and the urine collected during 10 periods of 20 min each. The urinary, sodium, and chloride flows were determined. The four groups displayed diuretic curves following a similar pattern. In contrast, the natriuretic curves of the four groups were completely different; totally flat with low values for the furosemide group and a large initial natriuretic curve for the hypersodic group with a gradual decrease but maintaining high values. The results indicate that the way the organism compensates for the excess of water by means of urinary water loss is independent of the body sodium content, whereas the way in which sodium loss is accomplished is determined by its body content and is independent of the way in which the water is lost. PMID- 1409936 TI - Ultrasonic vocalization of laboratory rats in response to handling and touch. AB - The goal of the study was to investigate the ultrasonic vocalization induced in freely behaving, naive rats by gentle touch with a human hand. Thirty-nine rats were tested in an unfamiliar experimental cage with repeatable hand touch. Vocalization appeared with an average latency of 4.6 +/- 5.0 s (SD). The nape of the neck was the most effective area, and after a couple of stimuli applied, 66.7% of rats emitted 21-32 kHz ultrasonic vocalization. It consisted of multiple series of long calls, about 70% of which exceeded 300 ms. The responses quickly habituated from session to session to extinction. Significantly more rats housed in single cages vocalized ultrasonically than animals housed in community cages. The long latencies of the vocalization, their appearance in multiple series to a single touch, and quick habituation to the stimuli indicate that 22 kHz ultrasonic vocalization of rats reflects a distress caused by a potential danger to the animal and it does not necessarily reflect physical discomfort or pain. This vocalization may, therefore, play an adaptive role in increasing chances of survival by conveying information about potential threats to other conspecifics. PMID- 1409937 TI - An automated method for recording scent marking in Mongolian gerbils. AB - A device for the automated recording of scent-marking events in Mongolian gerbils (Meriones unguiculatus) is described. The method uses minute temperature changes occurring at the surface of marked objects to detect scent marking. These events are recorded by a computer together with the exact time and the location of the marked object. The data obtained with this temperature-sensitive recording method correlate well with data obtained in parallel by human observers. The measurement of the diurnal rhythm of scent-marking behavior for 5 consecutive days in an undisturbed male demonstrates the specific usefulness of this new recording method. In addition, this temperature-sensitive automated recording of scent marking behavior may also be applicable in other animals that primarily mark protruding objects. PMID- 1409938 TI - Ibotenic acid lesion of the hypothalamic paraventricular nucleus produces weight gain but modifies neither preference nor aversion for saccharin. AB - We showed recently that bilateral ibotenic acid lesions of the lateral hypothalamus (LH) produced three main behavioral disturbances in the rat, i.e., an increase in the gustatory preference and aversion thresholds for saccharin, permanent body weight and water intake deficits, and an alteration of morphine induced modulation of taste. The two first results could suggest that the modification of the gustatory thresholds and the ingestive deficits are closely interrelated. Given this situation, we hypothesized that, conversely, a brain lesion known to induce obesity and hyperdipsia would therefore decrease the gustatory preference and aversion thresholds for saccharin. In order to test this hypothesis we analyzed the effects of the bilateral lesion of the hypothalamic paraventricular nucleus (PVH) by injection of ibotenic acid (2 micrograms in each side) on saccharin preference. The main results are as follows: 1) The neurotoxin selectively destroyed parvicellular neurons while the magnocellular cells were spared. 2) In comparison to the normal daily gain in body weight of the sham lesioned animals, the lesioned rats showed an enhanced weight gain that became significant from the third day after the surgery up until the day of sacrifice, 37 days later. 3) In contrast to electrolytic lesions of the PVH, the ibotenic acid lesions of this nucleus did not induce hyperdipsia. 4) Preference and aversion thresholds for saccharin were not significantly modified by the lesion. 5) Whereas low doses of morphine suppressed the preference for saccharin in sham lesioned rats when the concentration of the sweetener solution was at the threshold value, this suppressive effect was not observed in PVH-lesioned rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409939 TI - Sympathoadrenal function in genetically obese Zucker rats. AB - The effects of genetic obesity on the actions and alterations of the sympathetic nervous system were studied in 10-12-month-old obese (fa/fa) and lean (Fa/-) Zucker rats. Blood glucose, plasma insulin, epinephrine (E), norepinephrine (NE), and free fatty acids (FFA) concentrations were measured in blood samples taken through a permanent heart catheter before, during, and after exercise or intravenous infusion of E and NE. Baseline plasma FFA and insulin levels were markedly increased in the obese animals. Exercise, i.e., strenuous swimming against a counter current for 15 min, led to reduction of plasma insulin concentrations and an increase of all other blood components in lean Zucker rats. In obese animals, an exaggerated increase of blood glucose and a large suppression of plasma insulin occurred. Plasma FFA levels tended to decline during exercise. Plasma catecholamine patterns in the exercising fatty Zuckers were not different to those of the lean animals. Infusion of E caused an increase of blood glucose and a decrease of plasma insulin concentrations in both groups of animals. The increase in blood glucose in the obese animals was significantly larger compared to the changes in the lean animals. Infusion of NE significantly reduced plasma insulin concentration in obese but not in lean animals. The results revealed that activation of the sympathetic system, expressed as exercise induced alterations in plasma E and NE levels, is normal in obese Zucker rats. However, postsynaptic receptor effects of catecholamines on glycogenolysis and lipolysis are different in obese and lean animals, which points to permanent changes in adrenoceptor mechanisms on adipocytes, hepatocytes, and muscle cells in obesity. PMID- 1409940 TI - Altered sensitivity to NMDA following developmental lead exposure in rats. AB - Early Pb exposure is known to disrupt the development of the hippocampus and result in deficits in learning and memory capacities and altered seizure susceptibility. The excitatory amino acid, NMDA, is found in high concentrations in the hippocampus and has been implicated in learning and memory functions and seizure activity. Rat pups nursed mothers exposed to high (4%), moderate (0.4%), or low (0.05%) levels of PbCO3 in their diet, or a Na2CO3 control diet from postnatal day 1 (P1) to P25. Rat pups were injected with varying doses of NMDA on P15 or P25. Control animals showed a characteristic slowly developing response to NMDA, usually including tail twitches and wet dog shakes at approximately 10 and 40 mg/kg at P15 and P25, respectively, with status epilepticus and death occurring at 40 and 80 mg/kg. Lead-exposed animals displayed an altered sensitivity to NMDA, with high and medium Pb animals showing the onset of behavioral signs and death at lower NMDA doses, the degree of which being dependent on the level of Pb exposure. Low Pb-exposed animals showed a more variable and attenuated response to NMDA. The data are discussed in terms of the possible mechanisms of Pb neurotoxicity. PMID- 1409941 TI - Maternal behavior induced in male rats by bilateral lesions of the bed nucleus of the accessory olfactory tract. AB - In the present study, we investigate the effect of bilateral electrolytic lesions of the bed nucleus of the accessory olfactory tract (BAOT) in male Wistar rats that did not have care-pups experience, using a test of induced maternal behavior. Consistent with our previous findings in virgin female rats (10), there was a significantly shorter sensitization (3 days) and retrieval (2 days) latencies in the BAOT-lesioned group than in the sham-lesioned and intact-control male groups (12 days for both). Based on these findings, we propose that BAOT, a sexually dimorphic nucleus of the vomeronasal system, exerts an inhibitory modulation in the expression of parental behavior in male and female virgin rats. It may do so by maintaining an olfactory-based tonic inhibition of maternal behavior, thereby resulting in the adults' tonic avoidance of the pups until this inhibition is abolished by lesion, or reduced or overridden by appropriate hormonal and/or sensory influences. PMID- 1409943 TI - Metabolic mechanisms involved in the impaired insulin secretion in pancreatic islets isolated from exercised and fasted rats. AB - This study examined the metabolic mechanisms involved in the impaired insulin secretion by pancreatic islets isolated from fasted and exercised rats. Insulin secretion to glucose (8.3 to 16.7 mM) stimulus was lower in fasted (F), exercised (E), and fasted plus exercised (EF) rats as compared with the control group. The rate of glucose oxidation by isolated islets was reduced in F and EF rats, but it was not modified in the E group. In response to alpha-KIC (5, 10, 15, and 20 mM), insulin secretion was not different in EF and F rats, in comparison to controls, except in the E group, which showed values slightly higher. These findings suggest that changes in insulin secretion in fasted rats, associated or not to exercise training, might be a consequence of a reduced activity of the right-hand side of the Krebs cycle (from pyruvate to oxoglutarate), leading to decreased glucose oxidation. However, the exercise itself caused a significant decrease of insulin secretion without altering glycolysis and Krebs cycle activities. PMID- 1409942 TI - Glucose utilization and insulin binding in discrete brain areas of obese rats. AB - The present study was carried out to determine whether genetically obese Zucker rats present changes in brain glucose utilization and/or insulin binding when compared to their lean counterparts. Glucose utilization in the whole brain, determined by measurement of 2-deoxy(1-3H)glucose-6-phosphate, was significantly lower in obese than in lean Zucker rats. In order to precise the structure involved, we then used quantitative autoradiography methods after either (1-14C) 2-deoxyglucose injection or 125I-insulin incubation. In obese rats, local cerebral glucose utilization (LCGU) was significantly decreased in the external plexiform layer (-37%, p < 0.05), in the lateral hypothalamus (-23%, p < 0.05), and in the basolateral amygdaloid nucleus (-30%, p < 0.05). In contrast, no difference in specific insulin binding was found between the two genotypes in any of the areas studied. These results are consistent with some data showing a decrease of LCGU in hyperinsulinemic rats. All together, these data show perturbations of glucose utilization, particularly in structures linked to the regulation of body weight and food intake in obese Zucker rats. PMID- 1409944 TI - Cohabitation with a sterile male facilitates the development of retrieval behavior in nulliparous female rats exposed to pups. AB - Female rats were housed with a sterile male or another female. After 3 weeks, half of the females that had been housed with a female were rehoused with an intact male. At the end of 6 weeks female or sterile male cagemates were removed. Intact male cagemates and pups were removed 3 to 12 h following parturition. All females were tested for retrieval of three unfamiliar pups placed in their cage on the day following removal of their cagemate. Three unfamiliar pups were placed with each female and the female's behavior observed for 10 min. Observations were made in this way for 13 days or until the female retrieved all three pups within the 10-min interval. Pups were left with the female on days they were not retrieved. Females housed with a sterile male reached criterion for pup retrieval in 2.9 days, significantly fewer days than were required for females housed with another female (6.6 days) but significantly more than were required for a postpartum female (0.8 days). By demonstrating that cohabitation with a male fosters the development of retrieval, these results support evidence from the study of aggressive behavior that pseudopregnancy facilitates the development of behaviors associated with pregnancy and lactation. PMID- 1409945 TI - Mineral balance and bone histology in spontaneously hypertensive rats. AB - SHRs (9 weeks old) were fed diets with or without extra NaCl (2%) and were given water or saline (1%) for 7 weeks. Food and liquid intakes were measured weekly. Blood pressure was determined at 9, 11, 13, 15, and 16 weeks of age. The values for body weight gain and food intake were not influenced by any treatment. Liquid intake greatly increased with the surplus of dietary NaCl. The blood pressure increased with age in all treatments. The increase in blood pressure was enhanced by the addition of NaCl to diet and water. Urinary potassium and calcium excretions were enhanced by added dietary NaCl and saline. Calcium content in the femoral bone was not changed by any treatment, although the number of osteoclast and the area of bone marrow were increased by saline supplementation. PMID- 1409946 TI - Inhibition by N-methyl-D-aspartic acid (NMDA) receptor antagonist of lordosis behavior induced by estrogen followed by progesterone or luteinizing hormone releasing hormone (LHRH) in the rat. AB - The effects of glutamate receptor antagonists on sexual receptivity induced by progesterone and LHRH were examined in ovariectomized, estradiol-primed rats (OVX EB). Enhancement of lordosis/mounts quotient (L/M) by progesterone (0.5 mg) or LH RH (150 ng; third ventricle, IVT) in OVX-EB rats was significantly decreased by IVT injection of (+) 2-amino-7-phosphonoheptanoic acid a competitive N-methyl-D aspartic acid (NMDA) receptor antagonist. On the contrary, there were no changes in L/M quotient after IVT injection of 6,7-dinitroquinoxaline-2,3,dione at two dose levels, a Non-NMDA receptor antagonist. The NMDA antagonist did not modify lordosis behavior in OVX-EB rats. The results indicate that the NMDA type of glutamate receptors appears to mediate progesterone and LHRH facilitatory actions and suggest that glutamatergic synapses may be involved in lordosis-facilitating neural mechanisms. PMID- 1409947 TI - Sexual pheromones in lipids and other fractions from urine of the male mole rat, Spalax ehrenbergi. AB - Spalax ehrenbergi mole rats are blind, solitary, territorial, aggressive, subterranean rodents with a yearly breeding season that peaks in December and January. We confirm here an earlier report that estrous females are attracted to substances present in the urine of homospecific as compared to heterospecific adult males. We have also found that nonestrous female mole rats show avoidance behavior to the same homospecific urine. Our objective was to ascertain the nature of the pheromone(s) and gain insight as to its possible role in reproductive isolation and speciation. An active principle, detected in either two- or three-choice behavior tests, was found to be extractable from urine by methylene chloride (CH2Cl2) and mainly found in the neutral lipid fraction. Total lipids were chromatographed by thin layer chromatography on silica gel G60 plates. Most of the activity was found in a zone bounded by Rfs 0.2 and 0.7. Cholesterol, other sterols, and ethyl esters of fatty acids chromatographed in this zone as determined by standards and staining. Ethyl esters of fatty acids were also detected in this fraction by GC/MS analysis. Although a large amount of activity was found in lipids, it only accounted for about 1% of that found in urine. Some activity may have been destroyed or lost during the extraction procedure and some may remain in a lipid insoluble form. Preliminary tests of lipid extracts of various portions of the male urogenital tract revealed pheromonal activity present, particularly in tissues associated with testes, epididymis, prostate, and bladder. PMID- 1409948 TI - Social facilitation of eating: effects of social instruction on food intake. AB - To investigate whether social influences cause increases in eating behavior, thirty undergraduate psychology students completed a diet diary for three 5-day periods. Subjects were instructed to either eat alone or eat with other people, actively eating with them for two of these periods. For the third period, subjects were instructed to eat as they normally would (with or without other people present). When instructed to eat with others present, subjects overall consumed more food, water, sodium, and alcohol than when they were instructed to eat alone. In the normal condition, food intake was 60% higher when the subjects ate with others present than when they ate alone. These results suggest that social facilitation has a causal influence on eating which increases food intake. PMID- 1409949 TI - The effects of olfactory bulbectomy and chronic psychosocial stress on serum glucocorticoids and sexual behavior in female rats. AB - The effects of olfactory bulb removal (OBX) and chronic psychosocial stress on serum glucocorticoids and sexual behavior were assessed in female rats primed with a subthreshold level of estradiol (E2). Ovariectomized females underwent either OBX or sham surgery. Half of the OBX and half of the sham animals were exposed to chronic psychosocial stress (crowding, strobe light, and intermittent noise) for one-half h per day for 27 days. On day 22, three blood samples were collected from each animal for serum corticosterone analysis; 1) before, 2) during, and 3) after acute stress (one-half h restraint). On day 28, females were exposed to either 4 or 24 h of E2. On day 29, all females received 500 micrograms progesterone (P) 4 h prior to sexual behavior testing. Sexual receptivity was measured using the lordosis quotient (LQ = [number of lordotic responses/10 mounts] x 100). Sexual proceptivity (dart and ear wiggling sequences) and rejection (number of nonlordotic responses to mount attempts) were measured throughout a 10-min test period. Results showed that chronic psychosocial stress dramatically increased sexual receptivity and proceptivity while decreasing sexual rejection in female rats primed with a subthreshold level of E2. Chronic psychosocial stress also elevated serum glucocorticoids and significantly exacerbated the glucocorticoid response to acute stress. OBX, while increasing sexual receptivity and decreasing sexual rejection, had no effect on serum glucocorticoids. These findings support the hypothesis that OBX potentiates female sexual behavior directly through an increase in neural sensitivity to E2. In contrast, the enhancing effect of chronic psychosocial stress on female sexual behavior may result from alterations of the hypothalamo-pituitary-adrenal system. PMID- 1409950 TI - Dimethyl disulfide mimics the effects of milk on fetal behavior and responsiveness to cutaneous stimuli. AB - This study examined the behavioral responses of near-term rat fetuses to a range of chemosensory fluids that resemble constituents of milk or are present in the context of suckling immediately after birth. Milk and dimethyl disulfide (DMDS), a constituent of pup saliva that promotes postnatal nipple attachment, were effective in altering fetal motor activity (increased mouthing and rearlimb movements after infusion), and producing changes in fetal responsiveness to perioral cutaneous stimulation (reduced incidence of facial wiping). The behavioral effects of DMDS were reversed by naloxone and the kappa receptor antagonist nor-binaltorphimine diHCl, suggesting kappa opioid involvement in these behavioral changes. The existence of prenatal responsiveness to DMDS suggests that this substance may function as a semiochemical during the neonatal period. PMID- 1409951 TI - Response acquisition with fixed and variable resetting delays of reinforcement in male and female Wistar rats. AB - Experimentally naive, food-deprived male and female Wistar rats were exposed to different experimental procedures in which response-independent food pellets were delivered as long as the rats did not press either one of the two levers in the experimental chamber. Once a lever was pressed, the presentation of response independent food was suspended for the remainder of that session and food pellets were delivered only after an unsignalled, resetting period of time from each lever press had elapsed. For five different groups of subjects there was either no delay between a lever press and food presentation, a fixed delay of 10 s or 30 s, or a variable delay of 10 s or 30 s. Response acquisition occurred most rapidly when a lever press was immediately followed by food presentation. Responding was also acquired when variable resetting delays of 10 s or 30 s or a fixed resetting delay of 10 s was inserted between a lever press and food presentation. When a fixed resetting delay of 30 s followed a lever press before food presentation some responding was observed, but not as much as in the other experimental conditions. The present results show that naive male and female Wistar rats will acquire a lever-press response when food presentation is contingent upon, but not immediately contiguous with a lever press. Consistent differences between the sexes were not observed. PMID- 1409952 TI - Interaction of estradiol, testosterone, and progesterone in the modulation of hormone-dependent aggression in the female rat. AB - Female rats that had become aggressive as a result of cohabiting with a sterile male were ovariectomized and implanted with Silastic tubes of estradiol, testosterone, and progesterone, estradiol and testosterone alone, or with empty tubes. The implants were designed to model serum concentrations present during the last week of pregnancy (estradiol, 0.06 ng/ml; testosterone, 2.6 ng/ml; progesterone, 70 ng/ml). Following a test of aggression 1 week postoperatively, estradiol and testosterone implants were replaced with ones designed to maintain the lower hormone levels present following parturition (0.02 ng/ml; 0.6 ng/ml, respectively). Progesterone was not replaced. At the first aggression test, females with estradiol and testosterone alone displayed significantly more aggression than females with these hormones plus progesterone. Both groups were more aggressive than females without hormone replacement. Following the exchange of large implants for small ones, females that previously had progesterone increased in aggression while females that previously had only estradiol and testosterone decreased in aggression. Both groups continued to be more aggressive than the group without hormone replacement. High serum progesterone present near the end of pregnancy appears to moderate the expression of aggression supported by estradiol and testosterone. Conversely, progesterone's decline at parturition appears to produce a rebound facilitation of aggression even though serum estradiol and testosterone simultaneously decline. PMID- 1409953 TI - Effects of chronic forced swimming and exposure to alarm substance: physiological and behavioral consequences. AB - Rats tested for 7 consecutive days in the forced swim test in fresh water were more immobile than those tested in soiled water on all days. Animals in both water conditions increased their immobility times slightly over days, but animals tested in soiled water, which presumably contained an alarm substance, never attained the immobility times of those tested in fresh water. When animals were switched between fresh and soiled water, they behaved exactly like animals in the water condition to which they were switched. Prior inescapable forced swimming in either water condition affected subsequent escape in a Morris water maze, but more so for animals tested only in fresh water. A second study corroborated the escape results. Serum corticosterone and relative adrenal weights were increased as a result of forced swimming but escape performance differences could not be attributed to differences in the stress-provoking consequences of the two water conditions. PMID- 1409954 TI - Effects of repeated maternal separations on the adrenocortical response to stress of preweanling rats. AB - Previous data indicate that the infant rat shows a marked increase in adrenocortical responsiveness to stress immediately following prolonged maternal separation. In Experiment 1 we studied the immediate effects of repeated maternal deprivation. Our results indicate that the increase in basal as well as stress induced corticosterone levels is a direct function of the length of the deprivation period immediately preceding testing, and is not cumulative. In Experiment 2 we examined the long-term consequences of maternal deprivation on adrenal responsivity. Four days following a single 24-h period of maternal deprivation, pups remained hyperresponsive to stress, although their basal levels of corticosterone had returned to control values. Shorter periods of deprivation (which did result in increased responsivity immediately following deprivation) did not have persistent effects. Our data suggest: 1) short periods of deprivation do not have a cumulative effect, and 2) there is a critical length of deprivation beyond which persistent changes in adrenocortical responsivity ensue. PMID- 1409955 TI - Salt appetite induced by DOCA treatment or adrenalectomy in rats: analysis of ingestive behavior. AB - A detailed description of the increased intake of 0.5 M NaCl solution by rats after systemic treatment with desoxycorticosterone acetate (DOCA) or after adrenalectomy was obtained by measuring feeding and drinking activity every 6 s for 23 h. In both models of salt appetite, the induced increase in saline intake occurred mostly at night and in close temporal association with bouts of eating and water drinking rather than in isolation. Consequently, there was no significant change in the total number of ingestive episodes, despite the substantial increase in the number of saline bouts. Saline drinking was in small draughts that usually were preceded by food bouts and followed promptly by water bouts. These and other observations indicate that under standard maintenance conditions of ad lib access to food and fluids, adrenalectomy and DOCA treatment each produce a relatively weak stimulus of salt appetite, and large daily intakes accrue because the animals do not remain satiated and the appetite recurs repeatedly. PMID- 1409956 TI - Muscle performance and adenine-nucleotides status in MCA-sarcoma tumor-bearing rats. AB - The reduction in DNA, RNA, amino acid, and total protein in muscle tissue of tumor-bearing rats may influence muscle function. The effects of MCA-sarcoma tumor burden on muscle performance and adenine nucleotides was evaluated in three fiber types of skeletal muscle. Twenty-one days after MCA-sarcoma tumor inoculation, the gastrocnemius-soleus muscle group of Fischer 344 rats was stimulated using an in situ preparation; tetanic stimulation for 10 min at 7.5, 15, or 30 tetani per min (TPM) or 60 TPM for 5 min (n = 6 control and six tumor bearing rats/group). ATP, ADP, AMP, IMP, phosphocreatine, and creatine content in white and red gastrocnemius muscle and soleus muscle was measured. There were no differences among controls and tumor-bearing rats in force output; however, ATP content in the soleus muscle of tumor-bearing rats was significantly reduced after 30 TPM for 10 min or 60 TPM for 5 min. The performance of skeletal muscle, over a wide range of stimulation frequency, in tumor-bearing rats does not appear to be influenced by changes in adenine nucleotide content. PMID- 1409957 TI - Sexual dimorphism in the effects of mating on the in vitro release of LHRH from the ferret mediobasal hypothalamus. AB - A sexually dimorphic pattern in the secretion of luteinizing hormone (LH) has previously been shown to occur in response to mating in an induced ovulating species, the ferret, with mating augmenting the secretion of LH in females but not in males. The aim of this study was to determine whether this dimorphic pattern in the postcoital secretion of LH reflects a dimorphic effect of mating on the neural release of luteinizing hormone releasing hormone (LHRH). The effect of mating on the in vitro release of LHRH from mediobasal hypothalami (MBH) collected from breeding male and female ferrets was studied. Luteinizing hormone releasing hormone release and content were significantly reduced in tissues from estrous females sacrificed 0.25 h after mating compared to unpaired estrous females and estrous females sacrificed 1 or 2.6 h after the mating stimulus. By contrast, the release of LHRH from MBH fragments and LHRH tissue content were equivalent in breeding males that were sacrificed 0.25 h after mating and in breeding males that were left unpaired. These data suggest that the postcoital surge of LH in the female ferret is preceded by a release of LHRH that initially depletes neuronal terminals within the MBH, whereas LHRH release, like pituitary LH secretion, is minimally affected by mating in males. PMID- 1409959 TI - Changes on plasmatic and erythrocytic magnesium levels after high-intensity exercises in men. AB - The aim of this paper was investigate the effects of high-intensity exercise on plasmatic and erythrocytic Mg levels in men. Twelve normal male volunteers participated in this study. The tests were performed on a cycle-ergometer (Monark). The exercise programs consisted of: 1) triangular progressive test (TPT); 2) interval endurance test (IET), of 45 min duration; and 3) maximal subtained test (MST), consisting of a maximal level, at 100% of MTP, for at least 7 min. The percent change in plasma volume (%PV) after exercise was calculated. Magnesium levels in plasma and erythrocytes were measured by atomic absorption spectrophotometry. No significant differences in the absolute Mg concentration of plasma were noted for the three maximal exercises. The percentage increase in plasma Mg concentrations was about 5-7%; however, percent decrease of PV was more important (13-16%). Erythrocytic Mg levels were increased after all maximal exercises (TPT, IET, and MST), although absolute Mg concentrations were not significantly different. PMID- 1409958 TI - Feeding behavior in rats fed diets containing medium chain triglyceride. AB - The effect of dietary medium chain triglyceride (MCT) on short-term food intake was compared with the effect of long chain triglyceride (LCT) in rats. Corn oil and glyceryl tricaprylate were used as LCT and MCT sources, respectively. Rats were given diets containing 200 g MCT/kg diet (MCT diet), 100 g MCT + 100 g LCT/kg diet (ML diet), or 200 g LCT/kg diet (LCT diet) in Experiment 1. Cumulative food intake was determined every h for the first 12 h, then at 2-h intervals thereafter during the subsequent 12 h. As early as 1 h after feeding, cumulative food intake significantly decreased in MCT-fed animals in a dose dependent fashion. In Experiment 2, rats were given a choice between MCT and LCT diets for 1 h to confirm whether or not the palatability of diets was influenced by dietary fat sources. There was no difference in food intake between the two diets. In Experiment 3, the responsibility of endogenous cholecystokinin (CCK) for the difference in food intake between the two diets was investigated for 6 h by using a CCK-A receptor antagonist, Devazepide (DVZ, 1 mg/kg b. wt.). Food intake in the MCT diet and also in the LCT diet was improved by DVZ. It is concluded that the satiety, but not the palatability, is affected by carbon chain length in dietary triglyceride sources, although the responsibility of endogenous CCK is very small. PMID- 1409960 TI - Analysis of walking locomotion in adult female rats undernourished as sucklings. AB - Suckling rats were undernourished from birth by underfeeding their mothers. They were refed from 3 weeks of age. Detailed analyses were made of the walking locomotion of previously undernourished and well-fed control female rats at 10 weeks, using electronic, computer, and TV techniques. Previously undernourished rats were found to deploy shorter stride times resulting in greater forward velocities. The shorter stride times were attained by reductions in stance time, while swing time was unaffected. No changes in stride length or width were observed, and the relationships between stride time and velocity, swing, or stance times were unaffected. PMID- 1409961 TI - Decreased performance in a delayed alternation task by rats genetically deficient in vasopressin. AB - Acquisition and retention of a delayed alternation task by rats genetically deficient in vasopressin (AVP) due to the homozygous occurrence of the Brattleboro diabetes insipidus (DI) gene (M520/DI) were compared to the response of rats that were heterozygous (M520/HZ) or normal (M520/N) with respect to the DI gene. No significant difference in the adaptation to the apparatus was observed between the groups. However, the rate at which the M520/DI rats acquired the alternation task was significantly slower than the acquisition rates of M520/HZ and M520/N rats. In addition, the maximum intertrial interval reached by the M520/DI rats was significantly shorter than the intertrial intervals reached by the M520/HZ and M520/N rats, indicating the ability to retain information was impaired in the M520/DI rats. These results are consistent with the hypothesis that AVP modulates the acquisition and retention of information for normal memory processes. PMID- 1409962 TI - Breast imaging and the augmented breast. AB - Women with augmented breast implants are presenting for mammograms in greater numbers over the past year due to recent publicity regarding the safety of silicone gel-filled implants. New issues are being raised in light of this recent increase, making it essential for patients and health care providers to understand the limitations of mammography and how to best minimize problems. PMID- 1409963 TI - Nursing in the 21st century. PMID- 1409964 TI - How to revise printed patient education materials. PMID- 1409965 TI - From your desk and back again: the publishing process. PMID- 1409966 TI - Hand assessment. AB - Health care personnel caring for a patient with an injured hand must fully understand the functional and structural anatomy as well as assessment methods involved with such an injury. This article will overview the importance of conducting a complete history and thorough examination of the hand as well as proper documentation procedures. PMID- 1409967 TI - Nursing management of patients following combined free flap mandible reconstruction. AB - Combined free flap mandible reconstruction can improve the quality of life for cancer patients both functionally and psychologically. Plastic surgical nurses have a unique role in empowering patients and helping them to regain their most personal basic needs. PMID- 1409968 TI - Amplification of plasmid (L factor) DNA and increased production of a plasmid gene product (gamma-interferon) in mouse L cells. AB - It has previously been reported that composite DNAs derived from L factor, a polyoma-related mammalian plasmid, can be established in several mouse cell lines after transfection. Here, we report that the copy number of a plasmid composite DNA consisting of L factor, pBR DNA, dihydrofolate reductase (dhfr) gene, and gamma-interferon (gamma-IFN) gene was increased more than 10-fold after two successive adaptations of the plasmid-bearing mouse L cells to increasing concentrations of methotrexate (MTX), an inhibitor of dhfr. The structure of the amplified L factor plasmid remained intact during prolonged cell culture, but the copy number remained to be amplified only when the selective pressure (presence of MTX in the medium) has been exerted during the culture. Cells bearing the amplified plasmid produced a higher level of gamma-IFN compared with the original clone, which was likely to be derived from the plasmid gamma-IFN gene amplified along with L factor and the dhfr gene. PMID- 1409969 TI - Complete nucleotide sequence of a Selenomonas ruminantium plasmid and definition of a region necessary for its replication in Escherichia coli. AB - A plasmid from Selenomonas ruminantium subspecies lactilytica has been subcloned in Escherichia coli K-12 and completely sequenced. Three open reading frames (ORFs) of 909, 801, and 549 bp were identified and the complete sequence was analyzed by comparison with DNA and protein databases. No significant deoxynucleotide or amino acid sequence homology with other published genes or proteins was detected. The plasmid was shown to replicate independently in E. coli K-12 by a DNA polymerase I-dependent mechanism and deletion analysis defined the DNA sequence responsible for this phenotype. PMID- 1409970 TI - Molecular, genetic, and functional analysis of the basic replicon of pVA380-1, a plasmid of oral streptococcal origin. AB - The 4.2-kb cryptic plasmid pVA380-1 has been used as a vector for the cloning of antibiotic resistance genes directly in streptococci, and in the construction of Escherichia coli/Streptococcus shuttle vectors. The results of subcloning experiments located the basic replicon of pVA380-1 within a 2.5-kb region. The nucleotide base sequence of this region was determined and contained a single complete open reading frame (ORF) encoding a 237-amino-acid peptide with a predicted size of 29 kDa. This peptide and a region of the DNA molecule 5' to the ORF encoding it shared homology with the replication protein and plus origin, respectively, of the Staphylococcus aureus plasmid pUB110. Data from Tn5 mutagenesis and complementation studies indicated that the protein product of the ORF was required for pVA380-1 replication in streptococci. Deletion of a region of the basic replicon distal to the plus origin and ORF produced an unstable derivative, and resulted in the accumulation of single-stranded replicative intermediates, consistent with the loss of a minus origin. All of these results suggest that pVA380-1 replicates by a rolling circle mode, and is most closely related to the pC194 family of single-stranded DNA plasmids. PMID- 1409971 TI - Physical map of the vitopine Ti plasmid pTiS4. AB - Within the Agrobacterium vitis group the vitopine strains represent a special subclass. Vitopine bacteria carry Ti plasmids with little or no homology with the well-characterized T-DNAs of Agrobacterium tumefaciens or Agrobacterium rhizogenes. The 262-kb Ti plasmid of the vitopine strain S4 was cloned and mapped. Homology studies with the octopine Ti plasmid pTiAch5, the nopaline Ti plasmid pTiC58, and the agropine/mannopine Ri plasmid pRiHRI identified several regions of homology. The origin of replication was localized to within 2.5 kb. PMID- 1409972 TI - Transfer of mobilizable plasmids to Sorangium cellulosum and evidence for their integration into the chromosome. AB - Recombinant vectors derived from the broad-host-range mobilizable plasmid pSUP2021 were constructed and transferred by IncP-mediated conjugation from Escherichia coli to Sorangium cellulosum, where they were integrated into the chromosome by homologous recombination and maintained stably. This appears to be the first system of gene transfer to S. cellulosum. PMID- 1409973 TI - Functional analysis of pAL5000 plasmid in Mycobacterium fortuitum. AB - Four of the five open reading frames (ORFs) present in Myobacterium fortuitum pAL5000 plasmid (ORF1, ORF3, ORF4, and ORF5) are dispensable for replication in M. fortuitum. However, two additional ORFs (ORF1 and ORF5) were necessary for replication in a Myobacterium smegmatis heterologous host containing an efficient plasmid transformation mutation. PMID- 1409974 TI - DNA sequence and analysis of a cryptic 4.2-kb plasmid from the filamentous cyanobacterium, Plectonema sp. strain PCC 6402. AB - The 4194-bp plasmid, pRF1, from Plectonema sp. Strain PCC 6402 was completely sequenced and analyzed. Seven potential open reading frames were identified. The predicted amino acid sequence of open reading frame C (ORF C) had identities of 34, 29, and 25% with Rep B from the Staphylococcus aureus plasmid, pUB110; Rep from the Bacillus amyloliquefaciens plasmid, pFTB14; and protein A from the S. aureus plasmid, pC194, respectively. A 75-amino-acid region conserved in these proteins (Rep B, Rep, and protein A) also was highly conserved in ORF C with identities of 45, 37, and 40%, respectively. Significantly, 16 of the 21 amino acids conserved in Rep B, Rep, and protein A were found at the same positions in ORF C. This ORF may encode a replication protein that includes a region conserved in some eubacteria. Additional structural features include a 425-bp region that contains palindromes, tandem repeats, and short direct repeats which may correspond to the origin of replication. An 18-bp inverted repeat was located between two open reading frames, A and G. PMID- 1409975 TI - Production of an immunoglobulin gene product by the plasmid expression vector L factor in mouse myeloma cells. AB - L factor, originally discovered in a subclone of mouse L cells, is a multicopy mammalian plasmid whose structure is related to that of polyoma. When a composite DNA consisting of L factor, pBR, bacterial neo, and an immunoglobulin (kappa) gene was introduced into mouse myeloma cells, the DNA was established as plasmids in the cells without rearrangement or integration into the chromosomes. The plasmid-bearing myeloma cells produced kappa mRNA and the gene product, kappa immunoglobulin, which were apparently derived from the gene located on plasmid L factor. These results suggest that L factor can be used as a plasmid expression vector for studies on gene expression and production of biologically active substances in mammalian cells. PMID- 1409976 TI - Stimulation of LH release from cultured pituitary cells by saponins of Petersianthus macrocarpus: a permeabilizing effect. AB - Aqueous extracts from stem bark of Petersianthus macrocarpus contain substances exhibiting both estrogenic and antiestrogenic potency. Triterpenic saponins were identified and extracted as a bulk. Their action on the in vitro LH released by cultured rat pituitary cells was investigated. P. macrocarpus saponins stimulated the LH release in a dose-dependent manner (from 10 micrograms/ml to 300 micrograms/ml). When added simultaneously, saponins and LHRH exerted initial additive effects on LH release, demonstrating independent mechanisms of stimulation. If cells were pre-treated with saponins for 15 min, the amount of LH released under a subsequent LHRH stimulation was lowered, presumably due to a partial depletion of the cells in hormone (data not presented). However, the action of saponins on LH release did not appear specific since a general permeabilizing effect of the cell membrane was evidenced both by trypan blue exclusion and by analysis of the total protein output. When using low concentrations of saponins (10 micrograms/ml), scanning electron microscopy did not reveal any significant alteration of the cell structure, which explains why the cells remain responsive to LHRH after withdrawal of saponins. With higher concentrations (greater than 30 micrograms/ml), the same analytical studies evidenced numerous perforations of the cell membrane, with subsequent cell death. Two highly purified saponin species were tested on LH release by cultured cells; one of them (petersaponin I) appeared responsible for the observed biological effects in vitro. But as cells were shown to be efficiently protected from saponin effects by the presence of serum, it may be concluded that saponins of P. macrocarpus extracts are probably not candidate molecules promoting the in vivo estrogenic and antiestrogenic effects. PMID- 1409977 TI - Effect of Galphimia glauca methanolic extract on neuropharmacological tests. AB - Galphimia glauca Cav. (Malpighiaceae) is used in Mexican traditional medicine for the treatment of nervous excitement. A methanolic extract from its aerial parts (MEGA) was tested in several neuropharmacological animal models including among others: hypothermic activity, barbiturate potentiation, protection against strychnine- and leptazol-induced convulsions. The combined data obtained from all biological models demonstrate the sedative property of this plant product. PMID- 1409978 TI - Diuretic action of aqueous Orthosiphon extract in rats. AB - An aqueous extract of Orthosiphonis folium, given orally, enhances considerably ion excretion in rat to a level comparable to that obtained with furosemide. No aqueretic action is observed. The increased ion excretion is not due to the potassium content of the starting material. PMID- 1409979 TI - Mitogenic activities in the protein fractions of crude drugs. AB - Eighteen different crude drugs were extracted with hot water and saline, and protein fractions were prepared from the extracts by ammonium sulfate precipitation. Mitogenic activities of the protein fractions were examined both on human peripheral blood lymphocytes and on mouse spleen cells. Potent mitogenic activities for both human and/or mouse lymphocytes were found in the protein fractions of four crude drugs, namely, Bupleuri radix, Pinelliae tuber, Sophorae radix, and Zedoariae rhizoma. Target specificities of these mitogens were investigated by using isolated T and B cells and lymphocytes from athymic nude mice. Sensitivity to protease digestion as well as water-soluble, ammonium sulfate precipitable nature assures that the substances responsible for the mitogenic activities are proteins. PMID- 1409980 TI - Stimulatory effects of ingenols from Euphorbia kansui on the expression of macrophage Fc receptor. AB - Immune complex binding to macrophages was enhanced by treatment with an E. kansui extract. Systematic fractionation of the extract led to the characterization of 3 O-(2'E,4'Z-decadienoyl)- and 3-O-(2,3-dimethylbutyryl)-13- O-n-dodecanoyl-13 hydroxyingenol as the active principles. Immune complex binding to macrophages by the action of these compounds increased in a dose-dependent manner. When each ingenol (10 nM) was added to the separated culture medium, the immune complex binding ability of macrophages increased up to 2-fold, respectively. Scatchard analysis showed the enhanced expression of the Fc-receptor for gamma-globulin by the action of each ingenol to macrophages. This Fc-receptor upregulation was dependent on RNA synthesis, suggesting a possible de novo synthesis. PMID- 1409981 TI - A peptide from Schumanniophyton magnificum with anti-cobra venom activity. AB - Using the chick biventer cervicis preparation as a bioassay for antivenom activity, a peptide has been isolated from the aqueous extract of the bark of Schumanniophyton magnificum. The peptide was isolated and purified by a combination of reverse-phase and exclusion column chromatography, preparative TLC, and HPLC. The peptide has a relative molecular mass of about 6000 daltons and is similar in amino acid composition to the cardiotoxins present in snake venom. The isolated peptide showed dose-related inhibitions of the effects of cardiotoxin and total venom of cobra species using the chick biventer cervicis preparation. PMID- 1409982 TI - Acetylenic glucosides from Microglossa pyrifolia. AB - From the leaves of Microglossa pyrifolia Lam. (Asteraceae) four new acetylenic glucosides (1-4) have been isolated. The aglucones 2a and 4a are new polyynes. The aglucone 3a could only be isolated as a mixture of E/Z-isomers in a ratio of 4:1. The structures of 1-4 were elucidated by spectroscopic and biochemical methods. Compound 1 shows antibacterial activity. PMID- 1409983 TI - An antiplatelet principle of Veratrum formosanum. PMID- 1409984 TI - Antiparasitic properties of diploceline, a quaternary alkaloid from Strychnos gossweileri. PMID- 1409985 TI - Cytotoxic activity of some triterpenoid saponins. PMID- 1409986 TI - Inhibitory effect of piquerol A on the growth of epimastigotes of Trypanosoma cruzi. PMID- 1409987 TI - [A new bufadienolide from Urginea pancration]. PMID- 1409988 TI - ACE-inhibitory procyanidins from Lespedeza capitata. PMID- 1409989 TI - Intraoperative physiologic blood flow studies in the TRAM flap. AB - An intraoperative study was done to establish the functional and quantitative properties of the blood supply to the TRAM flap through the assessment and manipulation of blood flow through the deep epigastric arterial system. Seventeen patients undergoing unilateral postmastectomy breast reconstruction with lower transverse rectus abdominis myocutaneous (TRAM) flaps were studied. The study is divided into two parts: (1) ultrasonic measurement of blood flow in the deep inferior epigastric artery (DIEA), and (2) direct measurement of blood pressure in the deep epigastric arterial system, after division of the deep inferior epigastric artery. With occlusion of the superior epigastric artery at the level of the upper edge of the skin flap, 71 percent of the patients had a decrease in the blood flow through the deep inferior epigastric artery, with an average decrease of 23 percent. This implies that the area of watershed perfusion in the lower TRAM flap is superior to the umbilicus, and therefore, survival of all lower TRAM flap tissues requires reversal in the normal direction of arterial flow to the flap. The blood pressure in the proximal stump of the deep inferior epigastric arterial system averaged 46 percent of the mean systemic blood pressure. Occlusion of the medial and lateral thirds of the isolated rectus muscle decreased the mean arterial blood pressure in the flap an average of 19 percent in 80 percent of the individuals studied. These data support the technique of harvesting the entire rectus muscle, avoiding muscle-splitting maneuvers that may compromise axial blood flow. PMID- 1409990 TI - Care of maxillofacial injuries: survey of plastic surgeons. AB - The purpose of this survey was to evaluate the current trends in the care of facial trauma. Data were obtained through the responses of a survey mailed to all those members and candidates listed in the 1989 American Society of Plastic and Reconstructive Surgeons Directory. A total of 2777 questionnaires were sent, with 1113 (40 percent) returned by means of a self-addressed envelope. Demographic results show that over 70 percent of the treating plastic surgeons fall within the age range 30 to 50 years. Although significant advances have occurred, treatment goals have remained unchanged. These center around the principles of accurate reduction and precise stabilization of fracture segments. The results of this survey reveal that a number of acceptable techniques were employed in the surgical repair of mandibular and zygomatic complex fractures. In the care of Le Fort III fractures, 59 percent of the respondents preferred the use of miniplates and screws for stabilization. Only 26.8 percent believed that facial fracture repair should be performed within the initial 24 hours. With frontal sinus fractures, the vast majority of plastic surgeons (82.1 percent) obtained a neurosurgical consultation. When the posterior wall was involved, 45.6 percent favored removal of the sinus mucosa, 29.7 percent obliterated the frontal sinus with a variety of autogenous materials, while 20.5 percent preferred cranialization. In summary, this survey shows a wide variation in the practice of facial fracture management within the plastic surgical community. PMID- 1409991 TI - The fate of plates and screws after facial fracture reconstruction. AB - Rigid plate and screw fixation is the mainstay of treatment for complex fractures of the facial skeleton. Complications of plate and screw fixation include prominence, infection, exposure, and migration. Five hundred and seven patients undergoing plate and screw fixation for facial fractures (1112 fractures) from 1983 to 1988 were followed for complications. Sixty-one patients (12 percent) required hardware removal. The location on the facial skeleton influenced symptoms and the rate of hardware removal. Infection and exposure may be decreased with antiseptic irrigations, avoiding mucosal damage, attention to proper mucosal closure, and correct placement of plates. Prominence may be decreased by the use of microplates in the supraorbital, frontal, and naso orbital-ethmoid locations. PMID- 1409992 TI - Analysis and results of treatment of established posttraumatic facial deformities. AB - The clinical records of 125 patients undergoing treatment for posttraumatic facial deformities (PTFD) from 1979 to 1990 were retrospectively reviewed. Patients with complex fractures had a combination of at least three of the major fracture categories [Le Fort I, II, III; naso-orbital-ethmoid (NOE); zygomatic; frontobasilar; and mandibular]. Twenty-five patients (20 percent) were found to have severe posttraumatic facial deformities resulting from a complex facial fracture pattern. Sixteen were males and nine were females, and their ages at the time of our first reconstructive procedure ranged from 22 to 64 years (mean 33 years). All patients presented to our clinic with severe posttraumatic facial deformities from 1 month to 26 years (mean 5 years) after original injury. The number of prior reconstructive attempts averaged two (range 0 to 9). Arbitrary severity scores assigned by us were mild in 4, moderate in 12, and severe in 9 patients. Once treatment was initiated in our clinic, the average number of operations was 3.76 until completion (range 1 to 15). Surgical treatment was aimed first at reestablishing proper skeletal, vertical, transverse, and sagittal proportions. Once skeletal foundations were reset, the more delicate naso-orbital ethmoid and lateral canthal relations were addressed. Of the 25 patients, 13 (52 percent) suffered a complication at some point during their surgical management. In these 13 patients, 20 complications occurred in a total of 94 operations for an overall complication rate of 21 percent. Fifteen of the 20 complications were related to infection. Skeletal abnormalities in patients with posttraumatic facial deformities can generally be corrected with current craniomaxillofacial techniques. Ultimately, an excellent result in terms of skeletal reconstruction is compromised by the status of the surrounding soft tissue. More in-depth knowledge of the nature and magnitude of the initial and subsequent soft-tissue injury will contribute to our ability to treat these disfiguring posttraumatic sequelae. PMID- 1409993 TI - Comparison of transcutaneous incisions used for exposure of the infraorbital rim and orbital floor: a retrospective study. AB - One hundred and five patients were investigated for functional and aesthetic impairments following treatment of orbital trauma through subciliary, mid-lower eyelid, or infraorbital incisions. The progress of impairments with time was assessed, and the merits and shortcomings of each of the three approaches were established. The results showed that impairments persisting up to 6 months postoperatively have virtually not receded even after 6 years. The infraorbital incision showed the highest frequency of impairments, followed by the subciliary incision. The mid-lower eyelid incision showed the best results, with an impairment frequency well below those of the other two approaches. This approach seems to combine the advantages of the infraorbital incision with the unnoticeable scar formation associated with the subciliary incision. PMID- 1409994 TI - Age-related changes of the craniofacial skeleton: an anthropometric and histologic analysis. AB - With the development of increasingly sophisticated methods for the alteration of bony facial form consequent to age, it is imperative that the surgeon have a fundamental knowledge of the age-related changes the skeleton may undergo. To understand these changes better, a detailed anthropometric and histomorphic analysis of the craniofacial skeleton as a function of age was undertaken. The study consisted of a detailed craniometric analysis of 160 skulls selected randomly from a Caucasian population of skeletal remains totaling 1500 specimens. Additionally, a histologic analysis of the supraorbital ridge in a separate preserved cadaver population was performed. Although the results showed individual variation as expected, definite changes in craniofacial morphology were observed. These included (1) appreciable reduction of facial height, most marked in the maxilla and mandible, and strongly correlated with loss of teeth, (2) modest increase in facial width, (3) modest increase in facial depth, except in those regions associated with tooth loss, and (4) general coarsening of bony prominences. Histomorphic analysis demonstrated increasing porosity with age, more marked in the female population. Although these changes represent population trends, in any given patient, any or all of them may be present to varying degrees. Surgeons should be aware of these possibilities and consider selective alterations of the skeletal foundation, either separately or in concert with the overlying soft-tissue envelope, in order to optimize the results of surgery for the aging face. PMID- 1409995 TI - Rhytidectomy and the nasolabial fold. AB - I describe a technical modification in the Skoog face lift procedure that releases the deep attachments of the SMAS to the muscles of facial expression for maximal mobility of the medial cheek yet elevates the cheek flap as a composite of skin, subcutaneous tissue, and SMAS to enhance skin perfusion. My results with the procedure in 100 patients are analyzed by using functional zones of the nasolabial fold corresponding to underlying musculature and a simple grading system based on preoperative and postoperative photographs. Marked improvement in the nasolabial fold was noted in over 80 percent of patients by 6 and 12 months postoperatively. This effect seemed to last up to 4 years. PMID- 1409996 TI - The external oblique flap for reconstruction of the rectus sheath. AB - Despite the availability of synthetic materials and distant fascial flaps, primary closure of ventral abdominal defects with contiguous tissues remains the preferred solution. Increased experience with such defects in the lower abdomen, particularly at the time of bilateral rectus muscle transposition, led in 1985 to the investigation of an external oblique abdominis flap for closure of the anterior rectus sheath. From October of 1985 to October of 1990, 33 patients underwent repair of bilateral lower rectus abdominis defects with the help of bilateral external oblique flaps. Each of the patients had undergone synchronous chest or breast reconstruction using a transverse rectus abdominis musculocutaneous flap including bilateral rectus muscle pedicles. Although all patients in this study had undergone double-pedicle rectus muscle procedures, not all patients having had double-pedicle rectus muscle procedures required this maneuver. External oblique flaps were performed at the time of rectus sheath repair only if fascia could not be approximated without tearing. After closure of the bilateral paramedian defect, synthetic mesh overlay was added only if the direct closure still appeared excessively tight. At the time of advancement of the external oblique muscle and fascia, the internal oblique abdominis muscle and lateral cutaneous nerve of the thigh were preserved. Of the 33 patients who underwent this procedure, 7 required the addition of mesh overlay. Thirty-two patients healed uneventfully with a remarkably solid ventral abdominal wall. One patient developed an early postoperative hernia subsequent to a major and prolonged abdominal-wall infection and abscess. Patient follow-up ranged from 1 to 36 months, with a mean of 12 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1409997 TI - Upper extremity impairment in workers performing repetitive tasks. AB - A series of subjective and objective measures were chosen to determine impairment of upper extremity function in 157 workers performing repetitive tasks. Workers were asked to respond to questions regarding their perception of the presence or absence of numbness, pain, weakness, or swelling in their upper extremities. Objective tests consisted of the measurement of grip strength, pinch strength, Semmes-Weinstein monofilament sensory responses, vibrometer responses, neurometer measurement, and the presence or absence of Tinel's or Phalen's signs. These measures were considered collectively to estimate the overall levels of impairment of each individual. Overall findings show that 55 percent of workers examined had impairment scores of 2 or more and 75 percent had scores of 1 or more. Significant differences were found in impairment ratings between job types. Those jobs requiring the highest repetition with the least rest per cycle had the highest impairment ratings. Workers that rotated jobs had impairment scores significantly less (p less than 0.005) than the average of workers performing single-task jobs. We conclude that cumulative trauma disorders are more prevalent than originally believed and that the disorder is best examined from an overall functional impairment perspective. PMID- 1409998 TI - Neonatal Volkmann's ischemic contracture of the forearm: a report of five cases. AB - We report five cases of children born with forearm wounds associated with motor and sensory losses to the hand and forearm. Their evolution toward muscle retraction is very similar to the classic description of Volkmann's ischemic contracture. These cases should not be confused with upper extremity gangrene of the newborn or aplasia cutis congenita. Two cases of neonatal Volkmann's ischemia have already been reported in the literature and identified as such. Another very similar case has been reported as upper extremity gangrene of the newborn, and three more cases of a forearm wound with neuromuscular involvement have been reported as aplasia cutis congenita. We believe that neonatal Volkmann's ischemic contracture of the forearm should be recognized as a separate entity. Its early diagnosis may improve treatment, especially for children with recent injury, in whom intracompartmental pressures may still be elevated. Early hand therapy and splinting are mandatory to minimize late sequelae. PMID- 1409999 TI - The role of local fasciocutaneous flaps in total burn wound management. AB - The majority of acute burn wounds or delayed reconstructions are best managed simply with a skin graft. However, if vascularized tissue is mandatory, the local fasciocutaneous flap may have an important role in providing a single-stage technique for obtaining tissue nearly identical in color, texture, and consistency to that of the defect being restored. This review of 182 consecutive burn patients needing surgery found that they underwent 233 separate episodes for skin grafting. Appropriately, only a fraction of this number required some form of vascularized flap, with 14 patients having 21 local fasciocutaneous flaps. Six were elevated in previously skin-grafted regions, which is an advantage peculiar to this flap type. Three flaps (14 percent) suffered major complications requiring a second surgical intervention. Only six of all flaps were used for acute burn wounds, but two of the three complications accrued in this subset, with one directly attributable to wound infection. Since most flaps were required for either coverage or release of contractures about joints, it has been recommended that the initial surgical approach for treatment of the acute wound in these regions be altered to preserve the fascial plexus whenever possible to permit the use of this simple and expedient alternative if it is needed later. PMID- 1410000 TI - Long-term histopathologic evaluation of human expanded skin. AB - Forty-two patients operated on by skin expansion have been contacted after a mean time of 25 months from the last surgery. Two biopsies have been taken from the expanded area of each patient. In 12 patients it has been possible to obtain a similar sampling from the opposite, nonexpanded area of the body. The samples underwent optic microscopy and cell kinetic and DNA content investigations. The epidermal structure of the followed-up skin, compared with the skin of the opposite side of the body, looks normal. The mitotic activity of the epidermal cells has returned to the values of preexpanded skin. The dermis shows a low degree of elastosis and zonal fragmentation of elastic fibers. The hypodermis, where the expander capsule was removed during the last surgery, does not show an accentuated fibrosis. PMID- 1410001 TI - The vasculature and clinical application of the posterior tibial perforator-based flap. AB - Use of the posterior tibial flap pedicled on the posterior tibial vessels has been described by several authors, but with it there is the major disadvantage of an unavoidable transection of the posterior tibial artery. To overcome this disadvantage, we anatomically studied the perforators from the posterior tibial artery and used posterior tibial perforator-based flaps clinically. Based on our anatomic study of 25 cadaveric legs, the cutaneous perforators were considered to be distributed from the distal to the proximal sides of the lower leg through the medial border of the tibia, and they were classified into three types: septocutaneous perforators mainly located in the distal third of the leg, muscle perforators located in the proximal half, and periosteal perforators in the proximal third of the leg. The average size and number of perforators was 0.8 mm and 3.1 in one leg, respectively. A considerable number were located at sites from 70 to 140 mm superior to the medial malleolus. Based on our clinical cases repaired with flaps, we consider this flap to be useful as a free flap for the repair of defects of the extremities and as an island flap for reconstruction of defects on the anteromedial aspect of the lower leg. The territory of the flap is relatively wide, being 19 x 13 cm. The long saphenous vein can be used safely as the venous drainage system in the case of free-flap transfer. PMID- 1410002 TI - Initial platelet deposition at the human microvascular anastomosis: effect on downstream platelet deposition to intact and injured vessels. AB - Initial platelet deposition (PD) in and around the region of a small-vessel anastomosis may set the stage for thrombosis and tissue loss. To study this problem, a human vessel model (human placental artery, HPA) has been designed to mimic the vascular injuries attendant on clinical microsurgery. To perform these studies, dissected lengths of human placental artery were treated to provide the following four types of injury: group I: control, dissected but otherwise uninjured (N = 5); group II: distal portion of vessel endothelium removed (N = 5); group III: central anastomosis, distal endothelium intact (N = 7); and group IV: central anastomosis, distal endothelium removed (N = 4). Vessels were perfused with 25 ml human whole blood for 17 +/- 5 s at an average shear rate of 536 s-1. Vessels in groups I to IV were segmented at 2-cm intervals, and the number of 111In-labeled platelets was measured. Data from the following groups of exposure zones were pooled and analyzed: endothelium intact, endothelium absent, anastomosis present, postanastomosis with endothelium intact, and postanastomosis with endothelium absent. Significant numbers of platelets were found to attach to intact endothelium, indicating that ischemia and microsurgical handling may augment platelet deposition to otherwise uninjured vessels. A similar degree of platelet deposition was measured after exposure of the subendothelium and perfusion, indicating that superficial subendothelial exposure in the absence of an additional prothrombotic stimulus may lead to no greater platelet deposition than occurs on slightly injured endothelium alone. Platelet deposition at anastomoses was strikingly elevated, although the anastomosis had no additive effect on platelet deposition to downstream endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410003 TI - Improving acute skin-flap survival through stress conditioning using heat shock and recovery. AB - We present our initial experience with a new method of increasing the survival of acute skin flaps through stress conditioning using heat shock and recovery. The heat-shock response is a basic form of stress response that exists on the cellular level. When cultured cells or whole organisms are exposed to supraphysiologic levels of heat, they respond by synthesizing a number of highly conserved proteins known as heat-shock proteins. These proteins have been shown to offer the cell or organism a survival advantage over nonstressed controls. The study demonstrates a significant survival advantage in acute dorsal skin flaps of Sprague-Dawley rats (p = 0.001). Study animals (n = 10) were subjected to a heating blanket set at 45 degrees C for 30 minutes and were allowed 6 hours' recovery before developing the flaps. Heat-shock protein was demonstrated in immunohistochemically stained sections of skin from the study animals but not in control animal skin (n = 14). We postulate that through stress conditioning a latent mechanism present within all cells was activated, thereby allowing the cells of our experimental flaps to better survive the stress of the acute flap model. PMID- 1410005 TI - Informed consent for all: the True Deal. PMID- 1410004 TI - Rx--CME: reduction medically necessary? PMID- 1410006 TI - Postburn breast reconstruction: tissue expansion prior to contracture release. AB - Tissue expansion of the scarred chest following burns results in a poor breast mound shape with little projection or inframammary fold, since the expander, like normal developing breast tissue, is kept flat by the scarred skin envelope. We present a case that demonstrates that adequate projection of the breast and formation of an inframammary fold can be achieved by expansion if extensive release and skin grafting of contractures over the breast mound are performed after expansion. Maintained expansion will act as a stent reducing secondary contracture of the grafted-areas. PMID- 1410007 TI - Successful bone grafting of fracture nonunion at the forearm radial flap donor site. AB - A case of donor-site fracture following a radial forearm flap was treated conservatively with plaster but failed to unite. Successful union was achieved with bone grafting, external fixation, and electrical stimulation. It is suggested that in similar cases of delayed union, or where a large amount of bone has been resected from the radius and there is a significant risk of fracture or where fracture has occurred intraoperatively, the possibility of primary bone grafting should be considered. PMID- 1410008 TI - Reconstruction of a complex defect of the hand with two distinct segments of the scapula and a scapular fascial flap transferred as a single transplant. AB - To repair multiple defects of the metacarpal bones in combination with skin defects, a combined scapular free flap on a single vascular pedicle--the subscapular artery and the accompanying veins--can be used successfully. This flap includes two distinct bone segments of the lateral border of the scapula and a scapular fascial flap. Because of its long and mobile vascular pedicle, such a transplant can be used for one-stage reconstruction of the first and other metacarpal bones of the long fingers of the hand. The scapular fascial flap included in the transplant provides good functional and aesthetic results in combined injury of the skin of the hand. PMID- 1410009 TI - Clinical application of peripheral nerve transplantation. AB - Surgical reconstruction of extensive peripheral nerve injuries frequently exhausts the patient's own source of expendable autogenous nerve grafts. Nerve allografts would offer a limitless supply of graft material. A 23-cm, 10-cable sciatic nerve allograft was performed in an 8-year-old boy in September of 1988. The patient was managed with Cyclosporin A for 2 years. Forty-four months after the transplant surgery and 19 months after the cessation of Cyclosporin A therapy, the patient has evidence of nerve regeneration across the allograft with recovery of functional sensibility in his foot. In the selected patient with an otherwise irreparable nerve injury, consideration can be given to the use of a nerve allograft. PMID- 1410010 TI - A method with three triangular flaps as a secondary operative procedure after reconstruction of the lower lip by Estlander's method. AB - We have devised a new method for secondary commissuroplasty after reconstruction of the lower lip using Estlander's method with both aesthetically and functionally satisfactory results. This method consists of forming two equilaterally triangular mucosal flaps on the vermilion and a small triangular skin flap in the new position of the commissure and transposing these three flaps to reconstruct the commissure. In the present paper, we reported the procedure and the results. This method produces extremely good results, obtaining favorable commissure form and reconstruction of the mucosa of both upper and lower lips without leaving an unnatural-looking color change in the mucosa or a step deformity in the vermilion. It can be expected that our method will improve the results of Estlander's operations after tumor resection in the lower lip. PMID- 1410011 TI - A new operation for velopharyngeal insufficiency: the palatoglossus myomucosal pharyngoplasty. AB - Myomucosal flaps employing the palatoglossi were used to correct posttonsillectomy velopharyngeal insufficiency because the palatopharyngeus were resected with the posterior tonsillar pillar. This new sphincter pharyngoplasty may have a role as a secondary option for treatment of velopharyngeal insufficiency. It should be remembered that this operation has only been performed in a single patient without cleft palate, and, therefore, its application in the cleft population and its potential complication rate are unknown. PMID- 1410012 TI - Microsurgical forearm "cricket bat-transformer" phalloplasty. AB - Presently, the donor flap of choice for microsurgical phallic reconstruction is the radial forearm flap. The success of several different design modifications confirms the reliability of the radial and ulnar forearm flaps. Farrow et al. described their experience with the "cricket bat" concept in 1980. To the previous "cricket bat" design, we now wish to add modifications. These modifications utilize longitudinal and transverse rotations of the linear forearm tissues to create a phallus--much like the transformation of a toy robot into a truck. Deepithelialized flaps and a full-thickness skin graft coronoplasty complete glans reconstruction. The "cricket bat-transformer" flap appears to produce the most predictable results in subtotal phallic reconstructions and phallic constructions in the pediatric and transgender patient groups. PMID- 1410013 TI - Impact of the journal Plastic and Reconstructive Surgery. AB - The "impact" of Plastic and Reconstructive Surgery was evaluated by bibliometric analysis. This technique considers the average frequency with which journal authors refer to articles published in Plastic and Reconstructive Surgery. The impact of Plastic and Reconstructive Surgery was compared with that of journals most commonly referred to within Plastic and Reconstructive Surgery as well as with that of journals read most commonly by Plastic and Reconstructive Surgery subscribers, such as the Annals of Plastic Surgery and the Journal of Hand Surgery (both American and British editions). The impact factor for Plastic and Reconstructive Surgery was at least twice as great as for any other journal related to this surgical subspecialty. With regard to other surgical subspecialties, while the impact factor for Plastic and Reconstructive Surgery was less than that of the Journal of Neurosurgery, Journal of Urology, and Journal of Ophthalmology, it was greater than those for orthopedics, otolaryngology, hand surgery, and dermatologic surgery. PMID- 1410015 TI - The future of facial augmentation. PMID- 1410014 TI - Auscultation--a dying art in plastic surgery. PMID- 1410016 TI - Proper CPT coding. PMID- 1410017 TI - Saline breast implant sloshing and bubble hydrostatics. PMID- 1410018 TI - Reconstruction of the upper eyelid with a subcutaneous pedicle flap. PMID- 1410019 TI - Galileo's revenge. PMID- 1410020 TI - Silicone gel implant failure. PMID- 1410021 TI - California ear plugs for rhytidectomy surgery. PMID- 1410022 TI - Silicone implants. PMID- 1410023 TI - Capsulectomy--medically or legally indicated? PMID- 1410024 TI - Caution advised regarding transconjunctival lower lid blepharoplasty. PMID- 1410025 TI - Endoscopic creation and repair of fetal cleft lip. AB - In utero repair of several life-threatening malformations in the human fetus is now a clinical reality, yet fetal surgery still poses significant risks to both the mother and the unborn child. Preterm labor is a major problem and is directly related to the large hysterotomy required for fetal exposure. Endoscopic surgical manipulation of the fetus, through small uterine "ports," solves this problem and may eventually permit fetal intervention for non-life-threatening malformations. In this pilot study we demonstrated the feasibility of performing endoscopic surgery on the fetus in situ. A lip incision was created and repaired using endoscopic microsurgical techniques in midgestation fetal lambs. This represents the first application of this technique for in utero fetal intervention. PMID- 1410027 TI - Free forearm flap for closure of difficult oronasal fistulas in cleft palate patients. AB - There were four patients with palatal clefts who had been operated on many times previously but who still had large oronasal defects due to wound disruption. Moreover, there was considerable scar in the residual palatal tissue, which was contracted in the anteroposterior dimension. These patients were treated with a radial forearm flap transfer. The technical aspects of this reconstruction are emphasized, especially methods to enhance primary healing and to facilitate in setting the flap. Three of the patients were successfully reconstructed with one operation. The fourth had a small area of dehiscence anteriorly that was later closed with advancement of the flap tissue. There were no other complications. With the replacement of healthy tissue, the palate could be pushed further back to achieve better repair of the muscle. This would contribute to better speech function. In every patient, nasal regurgitation was eliminated, and speech quality improved significantly. The radial forearm flap is ideal for intraoral use, providing thin, hairless skin with a long, large-caliber vascular pedicle. It can reconstruct defects in one stage with well-vascularized tissue and minimal dissection of the palate. In a select group of cleft palate patients, this free tissue transfer should be considered to achieve closure of large oronasal fistulas in patients with dense scar. PMID- 1410026 TI - A model for fetal cleft lip repair in lambs. AB - Fetal wounds heal without inflammation and scar formation. This phenomenon may, in the future, be applicable to human cleft lip and palate repair. However, extensive experimental work must first be done to document the benefits of in utero repair. We developed a large animal model for creation and repair of a complete cleft lip and alveolus using fetal lambs. The cleft lip and alveolus deformity was created in eight 75-day-gestation fetuses (term = 145 days) and either repaired in three layers or left unrepaired. There were four sham-operated fetuses, and all animals were alive at harvest. Repaired, unrepaired, and control fetuses were harvested at 7, 14, 21, and 70 days following surgery. The unrepaired fetuses demonstrated a complete cleft lip and alveolus with an oronasal fistula. The maxilla was asymmetrical, with the greater segment deviated toward the cleft and with decreased anterior maxillary width. In contrast, repaired cleft lip and alveolus animals showed no scar, normal thickness of the lip, and a symmetrical maxilla. Histologic analysis of the repaired wounds showed evidence of tissue regeneration without scar formation. The results of this preliminary study indicate that the fetal lamb cleft lip and alveolus model is technically feasible with an excellent survival rate. Healing occurs without scar formation. In the repaired animals, the maxilla was symmetrical. This model will be used to document facial growth following in utero repair of a cleft lip and alveolus. PMID- 1410028 TI - The radial forearm flap: a biomechanical study of donor-site morbidity utilizing sheep tibia. AB - The use of vascularized bone grafts to reconstruct extremity and mandibular defects is now commonplace in reconstructive surgery. Fibula, scapula, iliac crest, rib, and metatarsal as well as the radial forearm osseocutaneous flaps have all been utilized for this purpose. Troublesome spiral fractures of the distal radius are the most common fractures associated with the use of the distal radius as a vascularized bone-graft donor site. This study was proposed to investigate the effect of donor-site bone loss on the strength of the radius under torsional (rotational) loading. Previous clinical series and experimental studies have not examined this aspect of distal radius loading after harvesting the bone graft. Fifty pairs of sheep tibiae were utilized in the experiment. Five pairs were used in a pilot study and 45 pairs were used in the main experiment. Five pairs of human radii were used for the control in the pilot study. The pilot study attempted to make a comparison between the human radius and the sheep tibia for experimental purposes. For the biomechanical study of donor-site defects, four study groups were examined with random assignment and matched pairs. The control group (group 1) had no alteration to the bone. Each test condition included five matched pairs of sheep tibiae. Experiment 1 compared the difference in the depth of the osteotomy defect. In doing this, one-third of the total length of the bone was removed in each of the following specimens to include (1a) 30 percent of the cross-sectional area of the total bone, (1b) 37 percent of the cross-sectional area of the total bone, and (1c) 50 percent of the cross sectional area of the total bone. In experiment 2, the osteotomy shape was varied. Instead of the ends of the cuts being squared, the ends were beveled or rounded. Experiment 3 compared different lengths of bone removed in the osteotomy defect and included the following: In experiment 3a the diameter of the sheep tibia was measured at the incisura fibularis. This dimension was one diameter of bone, and a one-diameter length of bone was removed. In experiment 3b, a two diameter length of bone was removed. In experiment 3c, a three-diameter length of bone was removed. In experiment 3d, a four-diameter length of bone was removed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1410029 TI - Long-term results following velopharyngoplasty with a cranially based pharyngeal flap. AB - Between 1980 and 1989, 82 velopharyngoplasties have been carried out in the Department of Oral and Maxillofacial Surgery at the Medical University of Hannover. Speech results of 51 of these patients, including 39 patients with cleft lip and palate, could be followed up in the context of a clinical follow-up examination. Besides evaluation of speech results by two senior speech pathologists and two untrained listeners, a frequency analysis of the speech results with a sonograph was obtained. Nasal air loss was documented with a fogged-mirror test and computer aerometry. Whereas in 37 of 51 patients a normal or almost normal colloquial speech could be demonstrated, 30 of 39 patients with cleft lip and palate showed a normal or almost normal realization of the test sentences. Thirty of the 37 patients (81.08 percent) with normal or almost normal colloquial speech showed extensive mobility of the lateral pharyngeal wall. Symmetry of the velopharyngeal flaps seemed to have no influence on the speech result. With a fogged-mirror test, an average reduction of mirror fogging from 2.0 rings preoperatively to 0.9 rings postoperatively could be shown. In 31 patients, there was no longer any air loss postoperatively. Besides one rupture of a flap, two flaps had to be diminished in their lateral dimensions because of excessive size. We regard the cranially pedicled pharyngeal flap as an important operative procedure for improving speech results, especially in cleft lip and palate patients. PMID- 1410030 TI - An analysis of Le Fort I maxillary advancement in cleft lip and palate patients. AB - We present a series of 24 consecutive cleft lip and palate patients aged 16 to 46 years (mean age 27 years) who underwent Le Fort I maxillary advancement by the senior author over the past 8 years. Two groups, one of 12 patients with wire fixation and one of 12 patients with miniplate fixation, were evaluated. Each group had 10 unilateral and 2 bilateral clefts. All patients were grafted with autogenous bone (8 cranial, 14 iliac, and 2 mandibular). Horizontal advancement was 3 mm to 2 cm (with a mean of 7.8 mm). Vertical movement ranged from a shortening of 5 mm to a lengthening of 1.3 cm (mean 2.3 mm of lengthening). The amount and timing of relapse were compared in both the horizontal and vertical dimensions. The plated group was more stable in both the horizontal and vertical dimensions (p < 0.05). No significant skeletal relapses occurred after the first year. Statistically significant dental relapse occurred only in the wired group. Three patients developed transverse collapse of the small maxillary cleft segment, and four developed incisor angulation to compensate for maxillary skeletal relapse. The presence of a pharyngeal flap at the time of advancement appeared to increase relapse in both horizontal and vertical dimensions (p < 0.03), but there were too few patients (7 of 24) with pharyngeal flaps to prove this conclusively. We also concluded that pterygomandibular grafting is not necessary to achieve excellent results using miniplate fixation; autogenous grafting of the anterior maxillary osteotomy alone provides the necessary stability. PMID- 1410031 TI - The osteocutaneous free fibula flap: is the skin paddle reliable? AB - This clinical and anatomic study was undertaken to see if the skin paddle of the osteocutaneous fibula flap could be made more reliable. Eighty cadaver limbs were dissected to evaluate the type, number, and location of the cutaneous perforators supplying the lateral leg. Three types of perforators were identified: septocutaneous, musculocutaneous, and a type we termed septomuscular, which does not actually run within the muscle substance but is adherent to the muscle. Although not a true musculocutaneous perforator, it should be treated as such clinically. Musculocutaneous perforators were found to be more numerous and more proximal than the septocutaneous perforators. Eighteen clinical cases demonstrate a 33 percent skin paddle survival when dissected as a septocutaneous flap and a 93 percent skin paddle survival when dissected as a septomusculocutaneous flap. In using the osteocutaneous fibula flap, it is recommended that a cuff of soleus and flexor hallucis longus be incorporated into the flap to help ensure flap viability. PMID- 1410032 TI - Skin expansion in head and neck reconstructive surgery. AB - We used a tissue-expansion technique to achieve soft-tissue reconstruction in congenital and acquired defects of head and neck. One hundred and fifty-five head and neck reconstructions have been performed, with a 6 percent rate of major complications. We present our planning and surgical approach for single areas. From a technical point of view, the only major difference from the rest of literature is the approach to the problem of periprosthetic capsule. In fact, we believe that complete removal of the capsule, which can be achieved without vascular risk thanks to a special technique, is necessary to obtain the best results. PMID- 1410033 TI - Continuous versus intraoperative expansion in the pig model. AB - Continuous tissue expansion utilizing a continuous infusion device that maintains a constant expander pressure was previously demonstrated to be feasible and successful in obtaining rapid tissue expansion in a canine model. Intraoperative tissue expansion has been described and has gained some clinical acceptance as a method to gain rapid expansion. We compared the efficacy of continuous tissue expansion versus intraoperative tissue expansion in a piglet model. After completing a pilot study, continuous tissue expansion was performed in six pigs (14.5 to 20 kg) on one flank over a 3-day period utilizing an improved prototype device; at the termination of continuous tissue expansion, intraoperative tissue expansion was performed on the opposite flank. There were no complications or continuous tissue expansion device malfunctions. Intraoperative tissue expansion gave a true gain in area of 7.4 percent, while continuous tissue expansion produced a 22 percent gain (p < 0.02). When the effects of both recruitment and expansion were added, continuous tissue expansion gave a dividend of 286 percent versus 192 percent for intraoperative tissue expansion (p < 0.01). Biomechanically, intraoperative tissue expansion skin showed few differences from unexpanded skin, while continuous tissue expansion skin showed a significant increase in stress relaxation (47.78 versus 38.74) and decrease in breaking strength. Histologic analysis revealed some epidermal hyperplasia and inflammation surrounding the continuous tissue expansion expander and some vascular congestion over the intraoperative tissue expansion expander. We conclude that continuous tissue expansion is superior to intraoperative tissue expansion and that the prototype device may be useful clinically. PMID- 1410034 TI - Transcoronal blepharoplasty. AB - Some of the patients requesting blepharoplasty have a combination of excessive eyelid fat and brow ptosis but little or no dermatochalasis. Coronal brow lift, combined with transcoronal fat removal, serves these patients well. The prelevator fat pocket is easily entered from above by incising the periosteum of the anterior orbital roof just inside the orbital rim. Since the orbital septum and anterior lamella of the eyelid rim remain undisturbed, the result appears natural. Contraindications to the procedure include significant medical pocket fat and hair patterns that would exclude a coronal or hairline incision. Two complications, unilateral ptosis and unilateral chemosis, were temporary and totally reversible. Minor changes in the procedure have prevented the recurrence of these problems. PMID- 1410035 TI - Correction of the pinched nasal tip with alar spreader grafts. AB - A pinched nasal tip is caused by collapsed alar rims secondary to weak lateral crura. The resulting deformity can be corrected with alar spreader grafts- autogenous grafts of septal or auricular cartilage that are inserted between and deep to the remaining lateral crura to force them apart, propping up the caved-in segment. We describe the surgical technique, indications, and variations in design of alar spreader grafts and present representative results from our series of 38 patients. PMID- 1410036 TI - Problem neck, hyoid bone, and submental myotomy. AB - Despite significant attention to the cervical region over the last two decades, the hyoid bone has not received deserved recognition. In this report, the anatomy and role of the hyoid bone and suprahyoid muscles in cervicomental morphology are reviewed. From an analysis of cephaloxerograms on 54 patients, it was concluded that on a balanced neck, the most caudal border of the hyoid body is located at or above a line parallel to the Frankfort horizontal line passing through the most caudal border of the mandibular symphysis (menton). Of the muscles that control the position of the hyoid bone, the anterior belly of the diagastric, geniohyoid, and mylohyoid muscles pull the hyoid bone cephalad and anteriorly. The stylohyoid muscles, on the other hand, pull this bone cephalad and posteriorly, while the sternohyoid and omohyoid muscles pull it caudally. Transection of the first three muscles at their attachment to the posterior aspect of the mandible in patients with dysmorphic necks due to caudal and anterior hyoid position will allow posterior and cephalad relocation of this bone, which improves the neck contour. Sixteen patients, with an average follow up of 27 months, have undergone this procedure, with cervicomental contour improvement in all cases. The degree of improvement ranged from 1 to 5 (5 being excellent): One patient was ranked 1, two patients were ranked 2, two patients were ranked 3, and the rest were ranked 4 or 5. One patient had overcorrection as a result of an aggressive concomitant submental lipectomy. Another patient had central depression in the submental area. None of the patients had difficulties with mandibular movement or swallowing. PMID- 1410037 TI - Primary closure of human bite losses of the lip. AB - Human bite injuries of the lip have, because of the potentially contaminated nature of the wounds, been managed by delayed repair after an interval of about 3 months or more when the infection was controlled and the wound healed. On the contrary, from 1985 to 1990, at a plastic surgery unit in Nigeria, a developing country, 37 patients with human bite losses of the lip were managed by an aggressive approach utilizing (1) a 5-day course of antibiotics locally known to be effective against bacterial flora and (2) immediate surgical operation employing the diamond wedge excision method under local anesthesia with direct wound closure. The results have been so favorable that this method of management of human bite injuries is considered a treatment advance. PMID- 1410038 TI - Correction of type II breast deformities following conservative cancer surgery. AB - Breast deformities following conservative cancer surgery are seen with increasing frequency and often represent difficult reconstructive problems. Type II deformities are characterized by localized tissue insufficiency, which can be due to skin insufficiency (type IIa), subcutaneous tissue insufficiency (type IIb), or both (type IIab). Correction of a locally damaged breast is a surgical challenge that can result in a fully restored breast if selection of the surgical procedure is properly carried out. A series of 37 patients who underwent correction of type II deformities from 1980 to 1989 was reviewed. Results obtained with different surgical procedures, including simple submuscular placement of traditional or expandable implants, breast reshaping, transposition of a latissimus dorsi muscle or musculocutaneous flap, TRAM flap, and reverse abdominoplasty, were evaluated. Aesthetic outcome was judged to be good or excellent in 78 percent of patients. Guidelines for selection of the most appropriate surgical procedure according to the defect's etiology, morphology, and location and to the breast's size and shape are presented. PMID- 1410039 TI - Reconstruction of the radiated partial mastectomy defect with autogenous tissues. AB - As conservative surgery and radiation therapy have become accepted treatments for early-stage breast cancer, increasing attention has focused on the cosmetic results of this technique. When partial mastectomy--a term which encompasses a diversity of excisional techniques--is followed by radiation therapy, breast defects characterized by parenchymal loss, nipple-areola complex distortion, and cutaneous abnormalities can occur. From 1981 to 1990, eight patients sought reconstructive correction of a radiated partial mastectomy deformity. Patients were from 42 to 70 years of age (mean 49 years). All had breast cancer, except for one patient with diffuse and chronic breast abscesses. Six patients were reconstructed with latissimus dorsi flaps and two with rectus flaps. No patient underwent reconstruction sooner than 1 year after completion of radiation therapy; for the entire group, a mean of 2.6 years elapsed from completion of radiation therapy to flap reconstruction of the breast. Mammograms were obtained on all the breast cancer patients before and after the myocutaneous flap procedure. Follow-up extended from 1 to 9 years after reconstruction (mean 3.6 years) and included both physical examination and serial mammographic evaluations. Myocutaneous flap reconstruction with either latissimus or rectus flaps achieved an aesthetic improvement of the partial mastectomy deformity in all eight patients. Complications consisted only of seroma formation in two patients following latissimus flap reconstruction. Mammographic evaluation revealed fibrofatty degeneration of the soft tissues of both types of flaps, a change that occurs as early as 6 months after operation and appears as a radiolucent area. The feasibility of mammography as a screening adjunct for recurrent cancer in this group of patients is demonstrated. Advantages of this technique of autogenous tissue reconstruction are improvement of contour deformities associated with conservative surgery and radiation therapy, preservation of normal, sensate breast skin, enhancement of symmetry with the contralateral breast, and avoidance of a prosthesis. PMID- 1410040 TI - Unpredictable growth pattern of costochondral graft. AB - Costochondral grafts have gained increasing popularity in reconstruction of the temporomandibular joint and condyle in children. This is a report on the long term follow-up of eight adolescent patients who underwent reconstruction of the temporomandibular joint and ramus for correction of hemifacial microsomia or trauma-related temporomandibular joint ankylosis during varying periods of growth. Six patients had hemifacial microsomia, and two suffered from posttraumatic temporomandibular joint ankylosis. Average follow-up was 80.4 months. Four patients had excessive growth of the graft, one patient had suboptimal growth, and three patients had no growth. In addition, one patient had undergone four procedures for significant graft overgrowth. Based on this study and review of the literature, we have concluded that the growth pattern of the costochondral graft is extremely unpredictable, ankylosis is a common problem following a temporomandibular joint reconstruction with costochondral graft, and mandibular overgrowth on the grafted site can actually be more troublesome than the lack of growth. Furthermore, maxillary growth is proportionately influenced by vertical mandibular growth of the graft, while the horizontal maxillary growth is not altered. Ankylosis is a result of ossification of the cartilaginous portion and the three-dimensional graft overgrowth, aggressively extending beyond the cartilage graft boundary. Based on this study, we recommend that this procedure be performed only on severe deficiencies. Adequate amounts of soft tissue should be retained between the skull base and the graft, and we further recommend harvesting the graft from the fourth or fifth rib, which may reduce the potential for overgrowth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410041 TI - Protective effects of coenzyme Q10 on ischemia-induced reperfusion injury in ischemic limb models. AB - We examined simple cold preservation of rat limbs in Euro-Collins' solution to elucidate the protective effect of coenzyme Q10 (CoQ10) on the ischemia-induced reperfusion injury in an ischemic extremity replant model. A total of 126 Lewis rat limb replants were performed. Limbs were amputated from donor rats and preserved at 4 degrees C in Euro-Collins' solution and were orthotopically grafted to isogeneic rats by microsurgical technique. In the experimental groups (n = 42), coenzyme Q10 (10 mg/kg) was injected intraperitoneally into the recipients about 1 hour before reperfusion. In the control groups (n = 84), the same dose of solvent was given by the same route. We evaluated vascular patency of anastomoses by direct observation or microangiogram and performed histologic examinations 7 days after replantation. In the control groups, the ischemic limit was 96 hours. Ischemic limbs treated with coenzyme Q10 showed a statistically significant (p < 0.05) improvement in vascular patency after 72 and 96 hours of ischemia. Histologically, bone viability with osteoblastic activity was maintained in coenzyme Q10-treated animals of the 72-hour ischemic group. We conclude that the protective effect of coenzyme Q10 on reperfusion injury is suggested in this replant model. PMID- 1410042 TI - Clinicopathologic studies on human epithelial autografts and allografts. AB - We compared the survival of cultured epithelial allografts and epithelial autografts applied to donor sites for split-thickness skin grafts. Before grafting, cultured epithelium was devoid of Langerhans cells (LCs) or lymphoid cells by immunohistochemical and electron microscopic examinations. The autografts attached to the wounds permanently, without any clinical evidence of rejection. In contrast, allografts, which were mismatched for MHC and blood-type antigens, appeared to adhere firmly only until day 7. By the second week, signs of graft rejection were apparent: The graft changed color, and the underlying dermis underwent "microerosion" and denudation. By the third week, the area formerly occupied by the allograft had the same coloration as ungrafted wounds and apparently had undergone reepithelialization by the host. Immunohistochemical and ultrastructural studies clearly demonstrated that host Langerhans-like cells (without Birbeck granules) appeared in both autografts and allografts. However, these cells were numerous and distributed widely throughout allografts, whereas they were scarce and confined to the basal layer of autografts. Typical Langerhans cells (containing Birbeck granules) were present in the prickle-cell layer of autografts by day 7. The present study strongly indicates that allografts of cultured epithelium are rejected. Furthermore, given the known ability of Langerhans-like cells to function as accessory cells in T-cell activation, our results point to a role for host Langerhans-like cells in immunologically mediated rejection of the epithelial allografts. PMID- 1410043 TI - As it was. PMID- 1410044 TI - Controlling intraoperative and postoperative nasal bleeding. AB - An indwelling nasal suction tampon is described that effectively controls both intraoperative and postoperative nasal hemorrhage. The significant benefits of this device are better intraoperative control for the surgeon and less complicated postoperative recovery. I do not have any financial involvement in this device, but I would like other nasal surgeons to benefit from its particular advantages. The device is available under the trade name Instant and may be obtained from Innovations by Westmed, 3351 E. Hemisphere Loop, Tucson, Ariz. 85706; (602) 294-7987. PMID- 1410045 TI - Preserving academic excellence at the medical centers. PMID- 1410046 TI - Caveats concerning tarsorrhaphies. PMID- 1410047 TI - Psychological factors in recurrent pressure sores. PMID- 1410049 TI - Correcting or overcorrecting nasolabial folds. PMID- 1410048 TI - Removal of stacked polyurethane-covered mammary implants. PMID- 1410050 TI - Exploiting explanting. PMID- 1410052 TI - Sidney Wolfe, David Kessler, and the FDA: medical clearinghouse. PMID- 1410051 TI - Osteogenic layer. PMID- 1410053 TI - A new method of deepithelialization in reduction mammaplasty. PMID- 1410054 TI - Adaptive hypertrophy of the digit after transposition. PMID- 1410055 TI - Skin graft as an alternative to Marlex mesh in conjunction with tissue expansion. PMID- 1410056 TI - Epidemiology of cancer in the United States. AB - Malignant neoplasms are responsible for more than half a million deaths annually and 22.5% of all deaths in the United States. Cancer is the second leading cause of death overall and the leading cause of death among Americans aged 35-64. Within the next decade it may become the leading cause of death. Cancers of digestive and respiratory organs are responsible for 53% of all cancer deaths. Certain subgroups are at elevated risk for various cancers. For example, sun sensitive or excessively sun-exposed young white adults, young black women, and elderly patients are at increased risk for cutaneous melanoma, breast cancer, and colon cancer, respectively. Black men have the greatest risk for both lung cancer and cancer of the prostate. Acute lymphoblastic leukemia and solid tumors of the brain and nervous system are the most frequent forms of malignancy occurring among children less than or equal to 14 years. Office screening is the traditional method for identifying cancer victims as early as possible. A suitable screening test should be rapid, simple, inexpensive, and impose minimal discomfort. There must be a window of opportunity available to identify the cancer during a detectable preclinical phase, and therapeutic modalities must be available to alter progression. An office screening test for cancer may have any one of four outcomes, and three of them are bad. False negatives are the worst adverse outcome because cancer remains undetected despite screening. An epidemic of lung cancer, caused by cigarette smoking, is occurring in all race and sex groups. If Americans stopped smoking, 87% of lung cancer deaths could be prevented. Tobacco abuse also is a major risk factor for cancer of the esophagus, larynx, and oral cavity. Cigarette smoking is a contributing factor for cancer of the bladder, kidney, and pancreas, and it has been associated with both cervical cancer and cancer of the stomach. Smoking and smokeless tobacco cessation endorsements, messages, and programs must be part of routine disease prevention and health promotion activities in every primary care practice. More than 1 million Americans became new cancer victims last year, and more than 1 million additional cases will be detected this year. Because of the striking variability in state and regional patterns of various forms of cancer, geographic location of a practice may influence the frequency of cancers seen. Four sites (breast, prostate, lung, colon, and rectum) were responsible for 55% of cancer mortality and 56% of all new cases of cancer detected during 1991.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1410057 TI - Cancer in socioeconomically disadvantaged populations. AB - This article presents a summary of the health status of the disadvantaged populations in the United States, with specific regard to the incidence, treatment, and mortality of cancer. It begins with an historical overview of health care for the poor in this country, and continues with an explanation of the risk factors prevalent, if not inherent, in the life-style associated with low socioeconomic status, such as poor diet, cigarette smoking, and ignorance of preventive health measures and screening techniques. It includes a discussion of the different types that are overrepresented in this population and of the barriers to preventive care and treatment that still exist. The most important of these is decreased access to continuous medical care because of a lack of health insurance and an overdependence on emergency room treatment for all health care. The final section reviews solutions that have been preferred by physicians, nurses, lawmakers, public health workers, and community advocates for the poor. The most important parts of the solution are patient education for preventive health care, disease warning signs, and screening techniques and an overhaul of the present system of providing health care to ensure equal access and treatment for all members of the society. PMID- 1410058 TI - Geriatric oncology. AB - The incidence and prevalence of cancer will continue to rise in the elderly. Malignancies can present differently and have altered courses in the elderly. Heterogeneity exists within the geriatric population, and chronologic age alone should not be used to exclude older cancer patients from consideration for standard diagnostic therapeutic approaches. Early detection of malignancies in the aged remains a problem, and geriatric screening issues are discussed. PMID- 1410059 TI - Risk factors for cancer. AB - It is no longer reasonable to divide cancers into those that are genetic in origin and those that are environmental in origin. With rare exception, carcinogenesis involves environmental factors that directly or indirectly exert a change in the cell's genome. Virtually all causes of cancer are multifactorial, sometimes involving an inherited predisposition to the carcinogenic effects of environmental factors, which include chemicals, ionizing radiation, and oncogenic virus. Carcinogenesis is a multistep process including induction, promotion, and progression. Initiation requires an irreversible change in the cellular genome, whereas promotion is commonly associated with prolonged and reversible exposure. Tumor progression results in genotypic and phenotypic changes associated with tumor growth, invasion, and metastasis. Most information on human cancer risk is based on epidemiologic studies involving both exposed and unexposed individuals. The quality of such studies depends on their ability to assess the strength of any association of exposure and disease and careful attention to any potential bias. Few cancers are inherited in a Mendelian fashion. Several preneoplastic conditions, however, are clearly inherited and several malignancies demonstrate weak familial patterns. Environmental factors may exert their effect on DNA in a random fashion, but certain consistent changes, including specific translocations of genetic information, are often found. Currently, there is great interest in the close proximity of certain oncogenes governing growth control to the consistent chromosomal changes observed. Such changes may represent a final common pathway of action for environmental carcinogens. Sufficient laboratory and epidemiologic evidence exists to establish a causal association of several chemical agents with cancer. The most important carcinogenic chemicals are associated with life-style factors, whereas agents related to other environmental, occupational, or medical exposure are numerically less important. Most chemical agents exert their carcinogenic effects as electrophilic reactants covalently binding to DNA. Certain agents such as asbestos are carcinogenic by virtue of their physical properties. Several short-term tests have been used to screen for chemical carcinogens. Whole-animal studies remain the standard for predicting carcinogen risk in humans, although major limitations in such studies exist. Ionizing radiation also exerts its carcinogenic effect through damage to cellular macromolecules including DNA. Excess cancer risk appears after a latent period of several years following exposure. Risk increases in approximately a linear fashion in proportion to the radiation energy, cumulative dose, and a variety of host biologic factors. The greatest source of average radiation exposure to the US population is from the uranium decay product radon.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1410060 TI - Smoking cessation in office practice. AB - There can be no question that smoking is a modern version of plague; that, as Camus points out, the public does not comprehend its true nature. As in the metaphorical community in Camus' narrative, the struggle of individuals against the pestilence (including official obstruction) is imperative. Physicians have multiple opportunities to join the war against tobacco. This article has shown how one may help individual patients in smoking cessation or interruption of its initiation and has suggested other activities by which physicians can become health promotion specialists. By assisting in the process by which smoking loses its appeal, educating community leaders and medical organizations, and becoming exemplars of prohealth activity, we can make a difference in the health of our communities and our patients. PMID- 1410061 TI - Principles of cancer screening for clinicians. AB - This chapter has outlined some principles of tumor growth, test characteristics, and the evaluation of screening technologies. We have emphasized that test specificity is the critical parameter in the evaluation of technologies because it is the healthy people who will suffer the most from the adverse effects of screening. We have also emphasized that the efficacy of a test is best evaluated by examining mortality reductions in comparable populations. The purpose has been to assist clinicians with their interpretation of the literature. Busy clinicians may not always have the time or inclination to do this themselves. In those cases they need to examine how organizations who make recommendations are coming to their conclusions because it is physicians, not organizations that will do the screening. In particular, it is important to ask the following: (1) Were criteria followed to justify the recommendations being made? (2) If so, what were they, and can the organization demonstrate that they are being met? (3) What perspectives and biases do the organizations bring to the judgments they inevitably have to make? (4) Do you share those perspectives? and (5) When the recommendation is adopted, can you guarantee that it will "first do no harm." PMID- 1410062 TI - Barriers and incentives of physicians and patients to cancer screening. AB - It is imperative that the health care system provide mechanisms to improve cancer control. The most effective way of limiting cancer morbidity and mortality is by prevention (modification of behaviors that increase cancer risk), and by early diagnosis in the asymptomatic stage of the disease, which allows for curative therapies. This article has enumerated barriers that make preventive and early diagnostic maneuvers more difficult for both patients and physicians. Some of the barriers are common to both patients and physicians, such as discontinuity of care. The barriers were discussed from both perspectives. Suggestions were made for modification of these barriers, so that incentives might make provision of the preventive and early diagnosis more likely. The incentives are attainable; however, to make improvements on a large scale will require the efforts of the public, physicians, and the health care system. It will effect physicians from the beginning of their medical education and through their entire practice. A large amount of effort directed at a focused population by a small team of health care workers can make a large difference in preventive care. This was shown effectively by a general practitioner in England who undertook a 15-month "campaign" on a "deprived" community, and raised the level of preventive care to that of an "endowed" community. This type of effort by an individual is desirable, but much smaller individual efforts directed over an entire population can have a much greater ultimate effect. That is why the efforts must be directed toward the primary care physician. These physicians care for the majority of the population, so if each primary care doctor increased current efforts of prevention by just three patients per day, then over the entire population inestimable improvements on preventive care would result. There is some evidence that improvements in preventive care are occurring. As further research is directed at how best to provide preventive services in the physician's office, our skills and effectiveness will improve. Each physician should accept as his or her responsibility the ongoing preventive needs of the population he or she serves. The prevention and early diagnosis of cancer can be coordinated in the office with episodic care to minimize costs. The necessary knowledge and technology are available, application is the key. By applying these in a cost effective way, we can hopefully attain control of cancer in the next decade. PMID- 1410063 TI - Skin cancer prevention and screening. AB - Prevention and early detection of skin cancers are crucial to reducing morbidity and mortality. Armed with the above information and with some experience, the primary care physician can understand risk factors and recognize common benign and malignant skin tumors. This allows the primary care physician to play a key role in teaching patients about skin cancer prevention and in screening patients for skin cancers. PMID- 1410064 TI - Breast cancer screening. AB - Breast cancer, as the second leading form of cancer death among women, causes significant morbidity and mortality. The primary care physician can help raise the survival rate of women with breast cancer by providing important screening procedures that will lead to early diagnosis and treatment. Screening mammography and regular breast physical examinations are the current screening procedures of choice. Although there is still considerable debate over the age and interval at which women should undergo screening (see Table 1 for recommendations from various organizations), the primary care physician's recommendation is the single most important factor and will certainly lead to a higher screening rate for women in the greater at-risk age groups. Judicious use of these screening procedures should allow primary care physicians to catch more breast cancers at an early, curable stage. PMID- 1410065 TI - Cervical cancer screening. Past success and future challenge. AB - Population screening for cervical cancer resulted in significant reduction in the morbidity and mortality from cervical cancer. An increased understanding of the relationship of HPV infection with cervical cancer and the natural history of cervical cancer precursor lesions further solidifies and expands the biological basis for cervical cancer screening. Pap tests in asymptomatic women remain the cornerstone of cervical cancer screening. Clinicians should be cognizant of the significant false-negative rate of Pap smears. Meticulous attention to proper Pap smear technique is necessary to maximize the sensitivity of the test. Further research is needed to establish the role of cervicography and HPV DNA hybridization techniques in cervical cancer screening. PMID- 1410066 TI - Screening for gynecologic cancer. Vulvar, vaginal, endometrial, and ovarian neoplasms. AB - The success of the Pap smear in screening for cervical cancer illustrates many of the tenets of screening for disease. Unfortunately, no other gynecologic malignancy shares this success. Detection of most gynecologic malignancies occurs once they have become symptomatic and on clinical examination at the interval cancer-related checkup as recommended by the ACS. These examinations, done yearly in women older than 40 and every 3 years in younger women, can go a long way in the detection of genital tract disease. In detecting vulvar neoplasms, visual inspection of the entire perineum coupled with palpation to include Bartholin's glands and early biopsy of suspicious vulvar lesions promotes earlier diagnosis. Self-examination similar to breast self-examination and increased patient awareness are potential education goals for physicians as well as cancer and medical societies. Vaginal examination at the cancer checkup should continue. The finding that most vaginal cancers are picked up by abnormal cytology while they are still asymptomatic argues strongly for Pap testing after menopause. The knowledge that women who are status posthysterectomy for benign disease are not protected from developing vaginal cancers mandates continued Pap testing in this population as well. Because endometrial cancer is common, primary care physicians should maintain a high index of suspicion. Aspiration biopsy is a simple office based procedure with low risk and good yield, and any woman in the perimenopausal and postmenopausal period who presents with atypical bleeding patterns should be evaluated. Although not recommended as a general screening test, the ACS does advocate endometrial sampling in the high risk woman at the time of menopause. The greatest challenge to primary care physicians may be the early detection of ovarian cancer. No single test is available, nor is any advocated in screening for this lethal disease. Currently, only periodic physical examination is recommended at the cancer checkup interval. Ultrasound, both transabdominal and transvaginal, may help in detecting adnexal masses, but is not sensitive enough to differentiate benign from malignant lesions. In this setting, and in the patient with suspected ovarian cancer, CA 125 and AFP may be helpful in determining which patients require surgical exploration. Women with positive family histories for ovarian cancer require greater vigilance and close follow-up with serial ultrasound and CA 125 determinations. As the population ages, cancer, which is primarily a disease of age, will continue to increase in incidence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1410067 TI - Colorectal cancer screening. AB - Colorectal cancer is a common and devastating disease. Many authorities recommend screening asymptomatic person, although the benefit of such screening is without scientific validation. Each of the screening modalities available has been examined, and their merits and shortcomings have been discussed. Surveys have indicated that primary care physicians generally agree with screening asymptomatic patients, but only a minority actually comply with the recommendations. Patient acceptance also varies. Thus, while specialty boards and panels of experts attempt to arrive at policies for the general population, primary care physicians must interact with the individual patient. Until data from ongoing prospective screening studies are available and cost-benefit issues are resolved, screening for colorectal cancer will remain at the discretion of physicians and their patients. There is insufficient evidence to support either continuing or discontinuing the recommended examinations for asymptomatic patients. The screening examinations can be recommended on the basis of a theoretical benefit, however. They can be performed with a minimum of risk of injury or side effects. Certain patients can be identified as being at above average risk and deserving of more consideration. If aware of the benefits and limitations of colorectal cancer screening, primary care physicians can decide how to implement colorectal cancer screening in their clinical practice. PMID- 1410068 TI - Plasma beta-endorphin and natural killer cell activity in major depression: a preliminary study. AB - Low concentrations of beta-endorphin have been found to enhance human natural killer (NK) cell activity in vitro. Both beta-endorphin and NK activity are changed by clinical depression. To evaluate whether circulating concentrations of beta-endorphin have a role in the in vivo modulation of cellular immunity in humans, we measured plasma beta-endorphin and NK cell activity in 14 depressed patients and 14 age-matched control subjects. In the depressed patients, both plasma beta-endorphin and NK cell activity were reduced to 76% and 57%, respectively, of the mean levels in the control subjects. In addition, beta endorphin showed a significant positive correlation with lytic units of NK cell activity in the combined group of all subjects and in the patient group (p = 0.04), but not in the control group. The study supports the hypothesis that circulating endorphin is correlated with NK cell activity in vivo. This correlation may be higher in the depressed patient group. PMID- 1410069 TI - Hormone responses to fenfluramine and placebo challenge in endogenous depression. AB - Plasma prolactin and cortisol levels after oral administration of d-l fenfluramine hydrochloride (60 mg) and placebo were examined in 24 endogenously depressed patients and 21 age- and sex-matched normal control subjects in a randomized, double-blind study. Prolactin levels were significantly increased by fenfluramine in both groups, but the response was significantly blunted in the depressed patients compared with the controls. This effect was partially dependent upon elevated baseline cortisol levels in the depressed group and was also influenced by a history of weight loss. Plasma cortisol levels were not increased by fenfluramine in either group. These findings confirm previous reports and suggest that patients with endogenous major depression are characterized by central serotonergic hyporesponsivity. The need to account for baseline effects on hormonal responses to putative serotonergic agents is supported by the findings; however, these effects appear to be less striking when endogenicity is a prominent clinical feature of the depressive syndrome. The apparently complex influence of weight loss on prolactin response to serotonergic challenge remains to be clarified as well as the role played by the bioavailability of the challenge drug and its metabolite. PMID- 1410070 TI - Behavioral engagement level, variability, and diurnal rhythm as a function of bright light in bipolar II seasonal affective disorder: an exploratory study. AB - Six patients with bipolar II seasonal affective disorder (SAD) and seven normal control subjects rated their moods in winter at six fixed times each week-day during 1 week of dim and 2 weeks of bright light. The scales rated represent the mood dimension specifically associated with depression, a dimension here called behavioral engagement (BE). Compared with controls, depressed SAD subjects (1) showed lower BE levels across all rating times of the day, (2) were more likely to show diurnal variation in BE, (3) displayed more between-day instability in BE diurnal rhythm, and (4) exhibited greater short-term lability (change within 3 hours) in BE. Bright light reduced or eliminated all group differences in BE level and variability. PMID- 1410071 TI - Blood levels of melatonin, serotonin, cortisol, and prolactin in relation to the circadian rhythm of platelet serotonin uptake. AB - Blood levels of melatonin, serotonin, cortisol, prolactin, and serotonin uptake by platelets were measured at 08:00, 14:00, 20:00, 02:00, and 08:00 hours in 10 healthy men who ranged in age from 27 to 35 years. The Km values of serotonin active transport by platelets were significantly correlated with melatonin blood levels. There were no other significant correlations. The secretion of steroid hormones and prolactin showed an increase at 02:00 hours; levels of prolactin decreased at 08:00 hours, but steroid levels continued to rise. This finding suggests either a direct effect of melatonin on serotonin active transport or the influence of the suprachiasmatic nucleus on serotonin uptake by platelets. It is also possible that there is a simultaneous decrease in serotonin uptake and decline from peak levels of melatonin due to the rise in steroid secretion. PMID- 1410072 TI - Phototherapy with broad spectrum white fluorescent light: a comparative study. AB - The principles of photobiology suggest that the antidepressant effect of phototherapy depends on the dose and spectrum of light. We investigated the effect of spectrum by comparing two broad spectrum fluorescent light sources with different spectral distributions. In a crossover design, 11 patients with seasonal affective disorder (SAD) were treated with broad spectrum fluorescent and cool white light for 7 days. Scores on the Hamilton Rating Scale for Depression were reduced from 22.5 to 8.1 with broad spectrum fluorescent light and from 23.5 to 8.8 with cool white light. The results suggest that both light sources are effective treatments. PMID- 1410073 TI - Effect of chronic antidepressant treatment with adinazolam and desipramine on melatonin output. AB - Output of melatonin or its main metabolite, 6-sulphatoxy melatonin, provides an index of noradrenergic activity in the pineal gland, which is of interest in major depression and during its treatment with antidepressants. Fifteen female depressed outpatients did not differ in levels of 24-hour urinary 6-sulphatoxy melatonin compared with 13 female control subjects. However, a subgroup of the depressed patients (n = 9) who were treated with desipramine showed a significant elevation of 6-sulphatoxy melatonin levels after 1 week of treatment and a return to baseline levels after 6 weeks. There was also a significant negative correlation between 6-sulphatoxy melatonin levels and symptom severity as measured by the Hamilton Rating Scale for Depression after 3 weeks of treatment with desipramine. The other subgroup of depressed patients (n = 6) were treated with adinazolam, a benzodiazepine with antidepressant properties. Despite comparable antidepressant effects to those achieved with desipramine, adinazolam was not associated with any apparent change in 6-sulphatoxy melatonin output during 6 weeks of treatment. There was also no correlation between 6-sulphatoxy melatonin levels and symptom severity. PMID- 1410074 TI - Increased prevalence of the cavum septum pellucidum in magnetic resonance scans and post-mortem brains of schizophrenic patients. AB - A cavum septum pellucidum (CSP) has been regarded as an incidental finding of little clinical importance. However, an association between this developmental anomaly and a diagnosis of psychosis has previously been reported. We determined the prevalence of the CSP in parallel studies of brain scans obtained with magnetic resonance (MR) imaging and in the post-mortem brains of schizophrenic patients compared with normal controls. We found a significantly increased prevalence of the CSP in both the MR scans and post-mortem brains of schizophrenic patients compared with controls. In the MR study, 17 of 81 (21%) schizophrenic patients but only 1 of 46 (2%) control subjects had a CSP. In the post-mortem study, 17 of 28 (61%) schizophrenic patients and 12 of 39 (31%) normal controls had a CSP. The increased prevalence of a CSP in schizophrenic patients further indicates that anomalous development of the limbic system is an important aspect of this disorder. PMID- 1410075 TI - Quantitative magnetic resonance imaging in heroin- and cocaine-dependent men: a preliminary study. AB - Quantitative magnetic resonance imaging (MRI) of the brain was performed in nine drug-dependent men with a primary diagnosis of opioid and/or cocaine dependence, and 10 age-matched, non-drug-dependent controls. Individuals were screened for the presence of gross cerebral abnormalities before T1 and T2 analyses. Regional T1 and T2 times were calculated on a single 5-mm thick axial slice positioned just below the caudal margin of the lateral ventricles, passing through the caudate and putamen. A voxel of interest (VOI) cursor was placed bilaterally within the putamen, caudate, frontal gray matter, frontal white matter, or posterior white matter. T1 and T2 values were determined for each VOI using an iterative chi 2 minimization program. T1 and T2 relaxation times did not differ significantly between the subject groups in any brain region studied. These results suggest that T1 and T2 relaxation times may not identify microstructural central nervous system changes resulting from chronic opiate and cocaine abuse. PMID- 1410076 TI - Topographic quantitative EEG amplitude in recovered alcoholics. AB - Topographic measures of electroencephalographic (EEG) amplitude were used to compare recovered alcoholics (n = 14) with sex- and age-matched control subjects. Delta, alpha, and beta activity did not distinguish the groups, but regional differences in theta distribution did. Recovered alcoholics showed more uniform distributions of theta amplitudes in bilateral anterior and posterior regions compared with controls. Because a minimum of 5 years had elapsed since the recovered alcoholic subjects fulfilled DSM-III-R criteria for alcohol abuse or dependence, it is unlikely these EEG theta differences reflect the effects of withdrawal. PMID- 1410077 TI - Segmentation techniques for the classification of brain tissue using magnetic resonance imaging. AB - A technique is described for classifying brain tissue into three components: gray matter, white matter, and cerebrospinal fluid. This technique uses simultaneously registered proton density and T2-weighted images. Samples of each of the three types of tissue are identified on both image sets and used as "training classes"; these tissue samples are then used to generate a linear discriminant function, which is used to classify the remaining pixels in the image data set. Effects of varying the location and number of training classes have been explored; six pairs of training classes have been found to yield a suitable classification. Interrater and test-retest reliability have been examined and found to be good. Intrascanner and interscanner reproducibility has also been evaluated; classification rates are reproducible within the same individual when the same scanner is used, but in this study poor reproducibility occurs when the same individual is scanned on two different scanners. The validity of the technique has been tested by examining correlations between traced and segmented regions of interest, evaluating correlations with age, and conducting phantom studies, in addition to using visual inspection of the classified images as an indication of face validity. From all four perspectives, the method has been found to have good validity. Additional applications, strengths, and limitations are discussed. PMID- 1410079 TI - Neurophilosophy. PMID- 1410080 TI - The role of macrophages in models of neurological and psychiatric disorder. PMID- 1410078 TI - Brain lithium concentration by 7Li- and 1H-magnetic resonance spectroscopy in bipolar disorder. AB - A method was developed to measure lithium concentrations in the human brain using in vivo 7Li- and 1H-magnetic resonance spectroscopy (MRS). Lithium concentrations measured by MRS in 10 lithium-treated bipolar patients were at the half level of those measured in serum. Serial measurements indicated that lithium concentrations in the brain increased markedly during manic episodes, while serum concentrations were unchanged. These findings suggest that in vivo measurements of lithium concentrations in the brain, combined with measurements of concentrations in serum, may be useful in monitoring the effects of therapeutic drugs. PMID- 1410081 TI - PET scanning and schizophrenia--what progress? PMID- 1410082 TI - Pagophagia, or compulsive ice consumption: a historical perspective. AB - Pagophagia, or the excessive consumption of ice or iced drinks, is popularly regarded as a novel manifestation of pica, which has emerged, predominantly in the USA, over the last 30 years. However, a sampling of historical sources reveals that not only are there warnings in the writings of both Hippocrates and Aristotle concerning the dangers of excessive intake of cold or iced water, but a series of medical works, from the sixteenth century on, incorporate discussion and illustrative case histories about the detrimental effect of immoderate usage of cold water, ice and snow, frequently in the context of disordered eating. PMID- 1410083 TI - Eye-tracking dysfunction in the affective psychoses and schizophrenia. AB - Smooth pursuit eye movements to a sinusoidally moving target were recorded using the electro-oculogram in 49 subjects with bipolar disorder, 19 with major depressive disorder and 61 with definite schizophrenia, and compared with 145 normal controls. The signals were analysed in the frequency domain to yield a signal to noise ratio that is known to relate to accuracy of smooth pursuit. Smooth pursuit was found to be significantly poorer in schizophrenics than in bipolars, major depressed or controls. Eye-tracking performance was independent of the effects of neuroleptics, tricyclic antidepressants or lithium, and was not altered by the severity of depression in the affective psychoses. There was a small, but significant worsening of smooth pursuit with age in controls and schizophrenics, but this did not account for the group differences. The results support the view that among the major psychoses eye-tracking dysfunction is specific to schizophrenia. PMID- 1410084 TI - Familial calcification of the basal ganglia: a case report and review of the literature. AB - Although calcification of the basal ganglia is a relatively common and asymptomatic finding on cranial computed tomography, familial idiopathic calcification of the basal ganglia (ICBG) is a rare disorder with neurological and behavioral manifestations. Attention has recently been drawn to the frequency with which cases are diagnosed as schizophrenic (Cummings et al. 1983; Lowenthal, 1986; Davison, 1987). We report a family in which a mother and son have ICBG, but while the son has a paranoid schizophrenia and intellectual deterioration, the mother shows no psychiatric illness. A review of the relevant literature suggests that psychosis is not as common as usually supposed, and may only be coincidentally associated with familial ICBG. Moreover, we find little convincing evidence that familial ICBG is an independent entity; instead, and in agreement with earlier authorities (Bruyn et al. 1964), we argue that published accounts and our own cases provide evidence that the condition is related to pseudo hypoparathyroidism (PHP) and, therefore, may be due to a defect in a guanine nucleotide binding protein. PMID- 1410085 TI - The relationship between depression and anxiety: construction of a prototypical anxiety and depression scale. AB - The question of the relationship between anxiety and depression remains to be solved. The fact that clinical pictures show substantial overlap makes it difficult, using conventional instruments, to distinguish between the co occurrence of anxiety and depression and overlap in definitions and measurement of the two syndromes. This calls for the construction of scales which exclude symptoms common to both syndromes and incorporate symptoms specific only to anxiety or only to depression; i.e. scales with maximum discriminant validity. This article describes the construction of two such scales based on PSE symptoms; a prototypical anxiety scale and a prototypical depression scale. In a sample of 134 non-psychotic psychiatric out-patients these scales show good reliability and validity, both as a measure of severity and as a screening device. Compared to the Hamilton anxiety and depression scales (HARS and HRSD), the correlation between the prototypical anxiety and depression scales is low. PMID- 1410086 TI - The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression. AB - Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P less than 0.05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P less than 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder. PMID- 1410087 TI - Bulimia nervosa and major depression: a study of common genetic and environmental factors. AB - A genetic analysis of the co-occurrence of bulimia and major depression (MD) was performed on 1033 female twin pairs obtained from a population based register. Personal interviews were conducted and clinical diagnoses made according to DSM III-R criteria. Additive genes, but not family environment, are found to play an important aetiological role in both bulimia and MD. The genetic liabilities of the two disorders are correlated 0.456. While unique environmental factors account for around half of the variation in liability to both bulimia and MD, these risk factors appear to be unrelated, i.e., each disorder has its own set of unique environmental risk factors. Thus, the genetic liability of bulimia and MD is neither highly specific nor entirely non-specific. There is some genetic correlation between the two disorders as well as some genetic and environmental risk factors unique to each disorder. Limitations and directions for future research are discussed. PMID- 1410088 TI - Early onset bulimia nervosa: who is at risk? A retrospective case-control study. AB - The aim of the study was to compare the clinical features and predisposing characteristics of patients with an early onset of bulimia nervosa with those with a more typical onset. Twenty-three cases of early onset bulimia nervosa (onset age 15 or below) were compared with 23 sex- and class-matched cases of typical onset (onset age 17 to 21) using a retrospective case-control design. No difference was found in eating symptomatology between the two groups. Deliberate self-harm was more frequent in the early onset group, and there was a trend towards more depression among their relatives. Inadequate parental control occurred more often in the early onset group, but other indicators of intrafamilial disturbance did not differ in the two groups. There was also a trend for the early onset group to be exposed to more cultural stress as a result of family migration. Early onset patients were found to have a higher loading on risk factors than typical onset patients. PMID- 1410090 TI - Parental representations of melancholic and non-melancholic depressives: examining for specificity to depressive type and for evidence of additive effects. AB - Several studies have suggested that 'anomalous parenting', as measured by the Parental Bonding Instrument (PBI), may be a differential risk factor to subsequent depression in adulthood--being irrelevant to melancholia but over represented in non-melancholic depressive disorders. Such a 'specificity' effect is confirmed in our current sample of 65 melancholic and 84 non-melancholic depressed patients. Secondly, we examine the risk to depression effected by exposure to one parent with an anomalous parental style, and the extent to which that risk is modified by characteristics of the other parent. We find clear evidence of additive effects with the risk to non-melancholic depression being raised by exposure to 'anomalous parenting' from two parents. Of the varying parental styles measured by the PBI, low parental care from both parents provided the highest risk to non-melancholic depression (being 4-7 time higher in one sample and 13-27 times higher in the other). PMID- 1410089 TI - The epidemiology of psychiatrist-ascertained depression and DSM-III depressive disorders. Results from the Eastern Baltimore Mental Health Survey Clinical Reappraisal. AB - Psychiatrists used a semi-structured Standardized Psychiatric Examination method to examine 810 adults drawn from a probability sample of eastern Baltimore residents in 1981. Of the population, 5.9% was found to be significantly depressed. DSM-III major depression (MD) had a prevalence of 1.1% and 'non-major depression' (nMD), our collective term for the other depressive disorder categories in DSM-III, had a prevalence of 3.4%. The two types of depression differed by sex ratio, age-specific prevalence, symptom severity, symptom profiles, and family history of suicide. Analyses using a multiple logistic regression model discerned that both types of depression were influenced by adverse life events, and that nMD was influenced strongly by gender, marital status, and lack of employment outside the home. Neither type of depression was influenced by income, education, or race. This study validates the concept of major depression as a clinical entity. Future studies of the aetiology, mechanism, and treatment of depression should distinguish between these two types of depression. PMID- 1410092 TI - Psychiatric morbidity in bus crews following violent assault: a follow-up study. AB - In a prospective study 22 bus crews who were victims of physical assault were assessed using standardized psychiatric instruments, followed up for 18 months and compared to a non-assaulted control group drawn from the same bus garage. At initial assessment the assaulted group, compared to the controls showed a significant increase in psychiatric impairment and distress (as measured by the GHQ-30 and IES respectively), with 23% of assault victims developing post traumatic stress disorder as defined by DSM-III-R. At follow-up, while high levels of both psychiatric impairment and distress persisted there was evidence that they may be separate phenomena. PMID- 1410091 TI - Coping subtypes for men with coronary heart disease: relationship to well-being, stress and Type-A behaviour. AB - We used cluster analysis to delineate coping subtypes in a sample of 166 men with coronary heart disease who completed the Antwerp out-patient rehabilitation programme. These subtypes were identified on the basis of three well-defined superordinate traits that were selected from a comprehensive taxonomy: negative affectivity, social inhibition, and self-deception. Using Ward's minimum variance method and the cubic clustering criterion, we identified four coping subtypes; low-negative affectivity (N = 48), high-negative affectivity (N = 30), inhibited (N = 62), and repressive (N = 26) individuals. The accuracy of the resulting classification was demonstrated across parallel data sets and was further validated against external, health-related correlates that were not included in the clustering. The identified coping subtypes were significantly related to self reports of subjective distress/perceived stress, ratings of Type A behaviour and anger-in, return to work, prevalence of chest-pain complaints, and use of minor tranquillizers and sleeping pills. The major findings of this study suggest that (a) male coronary patients represent a heterogeneous population with distinctly different coping subtypes, and that (b) a relatively small number of homogeneous subtypes can account for a substantial amount of variance in subjective well being, coronary-prone behaviour, and return to work. These findings indicate that psychosomatic research should focus on how superordinate traits interact within individuals and corroborate the appropriateness of a class model to describe coping styles of male coronary patients. It is argued that discrepant findings across studies of Type-A behaviour and hostility may be related to the coping subtypes of the subject sample. Further attempts to cross-validate this classification scheme and to examine its health-related correlates are needed. PMID- 1410093 TI - From the jumping Frenchmen of Maine to post-traumatic stress disorder: the startle response in neuropsychiatry. AB - The startle response is a universal and phylogenetically ancient reflex. Pathological exaggerations and modifications of startle underlie the symptomatology of a surprisingly diverse range of neuropsychiatric disorders, a fact that seems to have gone largely unappreciated. We review the available literature on the physiology of the normal human startle response and examine the neuropsychiatric conditions characterized by pathological startle. Startle epilepsy and primary hyperekplexia are considered as neurological disorders involving abnormal startle. Patients with hyperstartle and exotic culture-bound syndromes characterized by excessive startle are considered by the authors to represent extreme variants of the normal startle response. Post-traumatic stress disorder, drug and alcohol withdrawal states and schizophrenia all have abnormal startle as a clinical feature secondary to increased arousal and presumed disturbance of central neurotransmitter systems. The neurophysiological mechanisms by which abnormalities of the startle response may occur are discussed and a system of classification of neuropsychiatric hyperstartles is suggested. PMID- 1410094 TI - A longitudinal study of general practitioner consultations for psychiatric disorders in adolescence. AB - Patterns of psychiatric diagnoses given during adolescence to a group of individuals continuously registered with a single general practitioner in South London over 20 years were analysed first during 'early adolescence' and secondly during 'early adulthood'. Psychiatric diagnoses were found to be relatively common. Of the young adolescents who received a psychiatric diagnosis (almost one in ten of the group), 38% received a psychiatric diagnosis as young adults compared with only 16% of the remainder. Comorbidity was found to be very common- over 50% of young adults with a diagnosis of depression also had a diagnosis of anxiety and phobic neuroses. Young people with problems of a psychological nature therefore deserve more attention, particularly from the primary care team. PMID- 1410095 TI - Labelling and illness in primary care: comparing factors influencing general practitioners' and psychiatrists' decisions regarding patient referral to mental illness services. AB - GPs and psychiatrists from South Wales were asked to make decisions based on the information included in each of 16 vignettes describing depressed and anxious subjects. This information contained randomly assigned sex, psychiatric label, good and bad psychosocial context and age as well as eight different severity ratings of depression and anxiety symptoms. Our results showed that both GPs and psychiatrists were influenced in their decision making by the severity of the illness, but that GPs alone were also strongly influenced by the presence of male sex and by the presence of a psychiatric label. Good or bad psychosocial context had no influence on the GPs' referral decision, and previous experience in psychiatry or other vocational training had no detectable effect, but this may be because of the sample size. PMID- 1410096 TI - QALYs in mental health: a case study. AB - The applicability of the Charing Cross health indicator (CH-X) to the field of mental health was investigated in a community setting using descriptive statistics and principal components analysis. The CH-X is based on assessments of (i) distress and (ii) disability. Our results suggest that with respect to quality of life in mental health settings measurements of distress may be of greater importance than disability. In addition, the CH-X may be insensitive to variations in the severity of mental disorder and may primarily reflect physical disability as opposed to social disability. QALYs methodology may require the adoption of a multidimensional measure of health in order to fulfil its proposed role in comparing medical and mental health programmes. PMID- 1410097 TI - The general population prevalence of non-organic psychiatric disorders in subjects aged 85 years and over. AB - The prevalence of psychiatric disorders was investigated in all inhabitants over 85 years of age (N = 1259), residing in Leiden, The Netherlands. The study design consisted of two phases. In the first phase the Mini-Mental State Examination (MMSE) and the 12-item version of the General Health Questionnaire (GHQ-12) were used to screen for potential cases; in the second phase all potential cases and a sample of the non-cases were interviewed with the Geriatric Mental State Schedule (GMS). DSM-III diagnoses were made based on the GMS and on information obtained from caregivers. There was a high prevalence of organic disorders of 31% (95% CI: 27-35%). The estimated overall prevalence rate for functional disorders was 8% (95%) CI: 4-12%). This is an underestimate because organic and functional disorders are mutually exclusive in DSM-III. The prevalence rate estimated for the population at risk for functional disorders (i.e. the total population minus the organic cases) was 12% (95% CI: 6-18%). This is very similar to prevalence rates for functional disorders found in population based surveys in younger age groups. Therefore, in contrast with the dementias, there appears to be no increase with age for the functional disorders. PMID- 1410098 TI - Social class and minor psychiatric disorder in British Civil Servants: a validated screening survey using the General Health Questionnaire. AB - Major psychiatric disorder is more common in people of lower rather than higher socioeconomic status. This is less clear for the commoner, so-called minor psychiatric disorders, but these are more affected by tendency to report symptoms. To examine this the distribution of minor psychiatric disorder by employment grade measured by the 30-item General Health Questionnaire is reported from the first cross-sectional phase of the Whitehall II Study of 10,314 London based civil servants, men and women between 35 and 55 years. Validation of the GHQ in a random subsample stratified by grade and sex (N = 201) suggested that people in lower employment grades tend to under-report minor psychiatric disorder on the GHQ relative to those in higher employment grades. The prevalence of minor psychiatric disorder corrected by the coefficients from the validity study was greater in the lower employment grades than the higher employment grades particularly for men. This was echoed in grade differences in well-being measured by the Affect Balance Scale, and in symptoms and recurrent health problems. Overall, for women there were few clear-cut differences in minor psychiatric disorder by employment grade. The lack of social class gradient in women suggests that further exploration should examine women's role at work and their personal lives for the aetiology of minor psychiatric disorder. PMID- 1410099 TI - Mental health effects of job loss in women. AB - This paper reviews literature on the mental health effects of involuntary job loss among women. In addition, a prospective study of the effects of job loss on psychological distress in a cohort of blue-collar women is described. A total of 141 women, of whom 73 were laid off during the 12-month study period, were examined. The occurrence and duration of lay-off was significantly associated with increased depressive symptoms, but not anxiety-related symptoms, even after effects of pre-lay-off psychological symptoms, social supports and occupational stress were considered. There was no evidence that these effects of lay-off were moderated by other characteristics measured prior to lay-off. Among women who were laid off, those who reported poor levels of support from their husband or partner in the immediate aftermath of lay-off and those experiencing more financial difficulties during the lay-off had higher depression levels at follow up. The nature of the lay-off as a chronic psychosocial stressor is discussed. PMID- 1410100 TI - 'Mentally disordered persons found in public places'. Diagnostic and social aspects of police referrals (Section 136). AB - A survey over 2 years of all Police Referrals (Section 136 of the Mental Health Act 1983) in an inner-city health district identified 163 cases, with a core group of repeat referrals. Previous psychiatric admissions, a diagnosis of schizophrenia, social deprivation, and a bias towards young men of Afro-Caribbean ethnicity were key features. The difficulty of obtaining clear data and uncertainties within the law rebound unfairly on patients, police and psychiatrists. Section 136, while not inappropriate diagnostically, can be seen as highlighting unmet social and medical needs in the context of community care. The requirement for coordinated resources, including acute in-patient services sufficient for deprived populations and legal provision for treatment beyond a hospital's boundaries, seems paramount. PMID- 1410101 TI - The use of the Ways of Coping (Revised) questionnaire with parents of children with Down's syndrome. AB - The principal aim of this study was to assess the validity and usefulness of the Ways of Coping (Revised) questionnaire (Folkman & Lazarus, 1985) with a British sample of parents of children with Down's syndrome. Factor analysis yielded five subscales which were compared with those reported elsewhere. Other properties of the instrument were investigated. It was concluded that the instrument was potentially valuable to those investigating coping in families with special problems. PMID- 1410102 TI - Cotard delusion after brain injury. AB - A right-handed young man with contusions affecting temporo-parietal areas of the right cerebral hemisphere and some bilateral frontal lobe damage became convinced that he was dead (the Cotard delusion), and experienced difficulties in recognizing familiar faces, buildings and places, as well as feelings of derealization. Neuropsychological investigation while these symptoms were resolving revealed impairment on face processing tests. We suggest that these impairments contributed to his Cotard delusion by heightening feelings of unreality, and that the underlying pathophysiology and neuropsychology of the Cotard delusion may be related to other problems involving delusional misidentification. PMID- 1410103 TI - The Medical Research Council Unit in Child Psychiatry. PMID- 1410104 TI - Family dysfunction as a risk factor in the development of antisocial behavior. AB - Many studies have indicated a positive correlation between family dysfunction and subsequent cognitive and behavioral problems in offspring. The purpose of this study was to compare the family histories of 118 inmates with those of 45 college students and to document differential patterns. The possible social implications of the data are discussed as well as directions for further research. PMID- 1410105 TI - Need for achievement and performance on measures of behavioral fluency. AB - This investigation was designed to assess the relationship between a validated personality characteristic, need for achievement (nAch), and performance on measures of behavioral fluency. To infer this relationship, 50 neurologically intact college undergraduates were administered a questionnaire assessing nAch and a battery of tests including a short form of the WAIS and measures of behavioral fluency (i.e., verbal fluency). Statistical analysis indicated that subjects high on nAch obtained higher scores than subjects low on nAch on the measures of figural fluency and the WAIS Verbal Scale. No significant difference on verbal fluency was seen between the two groups. Secondly, the group high on nAch also had a higher mean Verbal IQ but not a higher mean Performance IQ as measured by a short form of the WAIS than did subjects scoring low on nAch. PMID- 1410106 TI - WAIS-R scatter with psychiatric inpatients: I Intrasubtest scatter. AB - Intrasubtest scatter values for eight WAIS-R subtests were estimated for a sample of 150 psychiatric inpatients and compared with those reported for a comparable portion of the WAIS-R standardization group by Kaplan, Fein, Morris, and Delis in 1991, using the normal deviate (z) test. The standardization group's intrasubtest scatter was significantly greater than those reported for the psychiatric inpatients on all subtests except Arithmetic and Information. These results suggested that, contrary to expectation, limited intrasubtest scatter may characterize WAIS-R protocols of psychiatric inpatients, while the presence of scatter may characterize normal WAIS-R performance. PMID- 1410108 TI - Moral development and behavior. AB - The study of moral development as well as the relation of moral development and behavior has been of great interest to many over the past half a century. While some studies have shown no association between one's moral development and behavior, some evidence indicates level of moral reasoning influences behavior. Over 16 selected studies postconventional principles of justice are likely to be more prosocial and law-abiding than those appropriate at the lower stages of moral development. PMID- 1410107 TI - Validity of the Threat Index. AB - The validity of the Threat Index was examined in a study of 42 students and 15 HIV+ clients. When completing the Threat Index, subjects rate the self and death on 30 bipolar adjectives. A count is made of the number of times the same adjective poles are used to describe the self and death. Uses of the same poles are called matches, while uses of different poles are called splits. The Threat Index is based on the assumption that splits indicate threat. Analysis showed that neither splits nor matches were usually threatening and that neither was necessary or sufficient for the experience of threat. These results did not support the validity of the Threat Index. PMID- 1410109 TI - Scores on the State-Trait Anxiety Inventory for children in a longitudinal study of pubertal Spanish youth. AB - Changes in scores on the State-Trait Anxiety Inventory for Children for a sample of 534 pubertal adolescents were longitudinally studied over a period of 4 years. Biological development and other variables were investigated. For the 310 boys, A trait scores decreased significantly with age. The 224 girls showed significantly higher scores than boys in all years of the study. No significant relationship was found between anxiety and pubertal maturity. The year-to-year persistence in symptomatology of anxiety ranged between 55.6% and 66.1% for girls and between 48.5% and 53.1% for boys. Girls showed bi- and tri-annual persistence between 31% and 50%, and boys between 13% and 27%. Neuroticism scores formed the best predictor of A-trait scores. Symptomatology of anxiety is not transient during early adolescence, so personality may provide a risk indicator in the development of anxiety. PMID- 1410111 TI - Inferred and expressed self-image of pupils rated by teachers as high and low in anxiety: a comparison of self-other ratings. AB - The association was examined between 98 third-grade pupils' expressed self-image scores and inferred self-image ratings from teachers. Significant self-other agreements were found with sexes combined. With sexes separated, significant self other agreements were found for the 52 girls, but not for the 46 boys. PMID- 1410110 TI - Jewish inmates: an atypical prison group. AB - 12 Jewish inmates scored significantly higher than 1497 non-Jewish inmates on a measure of intelligence, the Raven's Standard Progressive Matrices. Interview findings indicated that the present Jewish inmates were never very involved in the practice of Judaisn and were not strongly integrated into their local Jewish communities. PMID- 1410112 TI - Longitudinal examination of teachers' burnout in a school district. AB - Teachers in a rural school district were administered the Maslach Burnout Inventory three times over a five-year period. Teachers scoring high on emotional exhaustion and low on personal accomplishment were classified as "experiencing burnout." Across the three waves, the proportion of teachers meeting these criteria for burnout were 7%, 11%, and 11%, respectively. By grade, burnout was noted among 3%, 8%, and 9%, respectively, over time for senior high-school teachers; 7%, 7%, and 11% for junior high-school teachers; and 9%, 17%, and 12% for elementary school teachers. Interventions must consider grade-taught and are probably most cost-effective for elementary school. It is important to establish norms across time and across school settings to determine high-risk groups deserving interventions. PMID- 1410113 TI - Stability of parental nurturance as a salient predictor of self-esteem. AB - The relationship of parental nurturance to self-esteem for seven distinct adolescent and early-adulthood age groups (N = 784) was investigated. Analysis showed that even though mothers' and fathers' nurturance together were more strongly related to self-esteem during the junior high school years (R2 values greater than 50% were obtained in each of the junior high samples) than during the high school and college years (R2 values less than 40% were obtained in each of these samples), parental nurturance still remained a robust predictor of self esteem during these latter years. These results were discussed within the context of (a) the stability at different ages of the bases upon which one's judgments of self-esteem are made, and (b) parental nurturance as a stabilizing influence during the transitional years of adolescence and early adulthood. PMID- 1410115 TI - Unemployment, suicide and homicide in metropolitan areas. PMID- 1410114 TI - Evaluation of an intervention designed to improve patients' hospital experience. AB - The influence of a videotape, shown in a hospital admitting room, on patients' state anxiety and concerns about hospitalization was assessed in a preliminary study. For both state anxiety and specific concerns regarding hospitalization the pretest scores on each variable accounted for the preponderance of the variance in the posttest scores. In both instances, the intervention and the interaction of the intervention with the pretest scores accounted for less than 1% of variance in the outcome. While finding small effects to be significant for such a small sample (N = 93) is unlikely, the sample size was adequate to detect medium to large effects. More important was the fact that 73.33% of the videotape intervention group indicated that they did not watch the video, which leads us to the conclusion that this intervention as tested is not worthwhile. PMID- 1410116 TI - Normative expectations and the behavior of significant others: an integration of traditions in research on adolescents' cigarette smoking. PMID- 1410118 TI - Summer and school-term youth employment: ecological and longitudinal analyses. AB - The effects of summer versus school-year employment on self-esteem, peer relationships, and family social climate were investigated in a sample of 135 adolescents. Students were assessed the summer before entrance into high school and during the second semester of high school, using a longitudinal design. Cross sectional findings indicated that, during the summer, 52 workers possessed higher self-esteem than 79 nonworkers. Longitudinal analysis indicated that 10 girls who worked only during the school term reported increases in both stress and activity with peers. At our final assessment, the families of 49 students who did not work at either time had become more conflicted and less cohesive than families of all other students. The developmental implications of these results are discussed. PMID- 1410117 TI - Mental health locus of control in first-degree relatives of agoraphobic and depressed inpatients. AB - Mental health locus of control in 77 first-degree relatives of agoraphobic, agoraphobic and major depressed (comorbid), and depressed inpatients were studied. Relatives of comorbid patients externalized locus of control more to chance than did relatives of agoraphobic and of depressed patients. These results suggest that a tendency to externalize to chance is familially transmitted and may be a vulnerability factor for the development of the comorbid condition of agoraphobia and major depression. PMID- 1410119 TI - Perception of political candidates based on their stand on abortion and taxes. AB - This study investigated whether young voters would vote for and volunteer to work for the election campaign of a presidential candidate, given the candidate's background and positions on two major campaign issues. Findings indicate that, although voter-candidate agreement on a single issue may be enough for a voter to vote for a candidate, agreement on both issues may be necessary before a voter agrees to volunteer to work for the candidate's election campaign. PMID- 1410120 TI - Depression and suicidal ideation in African-American and Hispanic American high school students. PMID- 1410121 TI - Gender equality, legitimization of violence, social disorganization and rates of personal violence (suicide and homicide) in America. PMID- 1410122 TI - Relationships among critical thinking skills, academic achievement, and misconceptions about psychology. AB - Two groups of 60 students each were selected from introductory college psychology classes. One consisted of high academic achievers, the other of average achievers. They were given the McCutcheon Test of Misconceptions, a 65-item, multiple-choice test designed to measure common misconceptions about psychology. Subsequently, they were also given the Watson-Glaser Critical Thinking Appraisal. Both groups made many errors on the McCutcheon test, but high academic achievers made significantly fewer errors on both the McCutcheon test and the Watson-Glaser than average achievers. A stepwise multiple regression consisting of Watson Glaser subscales 1 (the ability to draw valid inferences) and 4 (ability to weigh and interpret evidence) and GPA successfully predicted McCutcheon test scores (R = .43). This suggests that even beginning students with high grades and good critical thinking skills are likely to harbor many misconceptions about psychology. PMID- 1410123 TI - Students' knowledge of AIDS and sexual risk behavior. AB - College students appear to be knowledgeable of the methods of transmission and risks of the AIDS virus. However, the reality of susceptibility to infection does not seem to have altered their conduct. In a study of 19 heterosexual college students, knowledge and intention do not appear to be good predictors of sexual behavior. Young people appear to continue high-risk sexual behavior even while knowledgeable of the risks of AIDS. PMID- 1410124 TI - Alcohol and creative writing. AB - A repeated-measures design was used to test for the effects of alcohol on creative writing as measured by use of novel figurative language. 11 male social drinkers participated in a creative writing task under two conditions, alcohol (high dose: 1.1 ml. ethanol/kilogram body weight) and placebo. In the alcohol condition, within-subject comparisons indicated significantly greater quantity of creative writing while intoxicated. These results were interpreted as supporting the belief that alcohol can reduce "writer's block," at least amongst nonalcoholic subjects. PMID- 1410125 TI - Assessment of preschoolers at-risk with the WPPSI--R and the Stanford-Binet L-M. AB - The purpose of this study was to provide data on the validity of using the WPPSI- R with 16 preschoolers who had been referred for psychological assessment. A comparison of the preschoolers' performance on the WPPSI--R and the Stanford Binet L-M was made. Children ranged in age from 3-0 to 6-0 years, with a mean age of 4-5 yr. The correlations between WPPSI--R and Stanford-Binet L-M scores were strong; WPPSI--R Verbal IQ and Stanford-Binet L-M IQ, r = .85; WPPSI--R Performance IQ and Stanford-Binet L-M IQ, r = .75, and WPPSI--R Full Scale IQ and Stanford-Binet L-M IQ, r = .82. For this very small sample of children whose mean IQ was significantly below average, the WPPSI--R appeared to assess validly their current intellectual functioning. Attention should be given concurrent and predictive validity as well as the efficiency of using the WPPSI--R with other and larger samples of referred children. PMID- 1410126 TI - Reliability data for a Greek translation of the Revised UCLA Loneliness Scale: comparisons with data from the USA. AB - A Greek translation of the Revised UCLA Loneliness Scale was internally reliable (alpha = .89), after eliminating Item 4, and significantly correlated with the English version (r = .94) for a sample of bilingual students. Weiss's distinction between social loneliness and emotional loneliness was also reliably identified in the Greek translation. Loneliness scores in Greece were significantly higher than in the USA. The translation seems to be sufficiently reliable to warrant further use with Greek individuals. PMID- 1410127 TI - Behavioral economics of drug self-administration. III. A reanalysis of the nicotine regulation hypothesis. AB - The maintenance of a characteristic level of nicotine in a smoker's body is referred to as nicotine regulation. Considerable research has examined this question of whether smokers regulate nicotine intake. This is because nicotine regulation raises the question of whether smokers who, to decrease their intake of tar, switch to low tar/low nicotine cigarettes will increase the number and/or intensity of cigarettes smoked. Although the results of studies examining nicotine regulation are reported as generally consistent, considerable variability exists across these analyses such that the health hazards of smoking low tar/nicotine cigarettes remains uncertain. In the present analysis, these studies were analyzed to ascertain whether a behavioral-economic interpretation could better quantify the effects of changing nicotine yield on individuals' nicotine and smoke consumption. Specifically, 17 nicotine-regulation studies were reanalyzed using a unit-price analysis (i.e., cost-benefit analysis). The reanalysis showed less variability across regulation studies than previously reported; a positively-decelerating demand curve was found across most studies, consistent with previous unit-price analyses of food- and drug-maintained behavior. The benefits of this reanalysis versus the traditional regulation interpretation are that the behavioral economics approach: 1) brings unity to a variable set of data, 2) shows a nonlinear relationship, previously considered to be linear, between nicotine consumption and nicotine yield, 3) shows that nicotine yields higher, and not lower, than the smoker's usual brand decrease smoke consumption and thus decreases consumption of the harmful agents in tobacco, 4) better quantifies the data and provides a more parsimonious interpretation that generalizes to other drugs and food-maintained behavior in humans and nonhumans and, 5) integrates behavioral and pharmacological factors that control the consumption of reinforcers. These results suggest the value of behavioral economics in the study of consumptive behaviors and clinically suggest, in agreement with the studies contained herein, that decreasing the smoker's usual nicotine yield can have potential health risks for smokers who are unable to stop smoking. PMID- 1410128 TI - Effects of a single dose of the acetylcholinesterase inhibitor velnacrine on recognition memory and regional cerebral blood flow in Alzheimer's disease. AB - The effects of a single oral dose of the acetylcholinesterase inhibitor velnacrine maleate on word and object recognition memory and regional uptake of 99mTc-exametazime were examined in patients with Alzheimer's disease. Word recognition memory was marginally improved 2 h after 75 mg velnacrine. With the same dose of velnacrine a relative increase in superior frontal uptake of 99mTc exametazime was shown with single photon emission computed tomography (SPECT). This suggests increased regional perfusion and metabolism as a consequence of cholinergic stimulation. The effect did not co-vary with the degree of memory improvement, but, instead, more cognitively impaired patients showed a greater increase in tracer uptake after velnacrine, suggesting cholinergic hypersensitivity in the brains of Alzheimer patients. PMID- 1410129 TI - Elevated corticosteroid levels block the memory-improving effects of nootropics and cholinomimetics. AB - Oral pretreatment of mice with aldosterone or corticosterone blocked the memory enhancing effects of piracetam, pramiracetam, aniracetam and oxiracetam in a dose related manner, without, however, impairing the animals' learning performance. The improvement of memory induced by physostigmine, arecoline, and tacrine (THA) was similarly inhibited. The fact that elevated steroid levels suppress the memory-enhancing effects of entirely different substances could indicate that these substances have a common site of action. In the light of new observations showing increased cortisol concentrations in Alzheimer patients, this steroid dependency of the effects of memory enhancers might explain why only a limited number of these patients respond to therapy with nootropics or cholinomimetics. PMID- 1410130 TI - Attenuation of chemically induced defence response by 5-HT1 receptor agonists administered into the periaqueductal gray. AB - The ability of 5-HT1 receptor agonists to modulate a chemically induced defence response has been studied in Lister hooded rats. Microinjections of the excitatory amino acid D,L-homocysteic acid (DLH) in both rostral and caudal dorsal periaqueductal gray matter (PAG) caused explosive motor behaviour characteristic of defence. This behaviour was quantified in terms of response duration, arena revolutions and number of defensive jumps. Direct administration into the PAG of either 5-carboxamidotryptamine (5-CT) or 8-hydroxy-2-(di-n propylamino) tetralin (8-OHDPAT) produced behaviours (decreased exploratory rearing, dose related onset of flat body posture) indicative of 5-HT1A receptor activation. Pretreatment with either 5-CT or 8-OHDPAT directly in the PAG caused a significant attenuation, and in some cases a complete abolition, of the DLH evoked response. These agonists share high affinity in vitro for the 5-HT1A receptor. Thus the results suggest that in vivo activation of 5-HT1A receptors mediates an antiaversive response with respect to defensive behaviour elicited by specific chemical stimulation of the dorsal PAG. PMID- 1410132 TI - Role of spinal serotonin1 receptor subtypes in thermally and mechanically elicited nociceptive reflexes. AB - The ability of 5-HT1A and 5-HT1B agonists to alter a spinal animal's nociceptive threshold was examined using two analgesiometric tests. In the spinal withdrawal reflex test, administration of the selective 5-HT1A agonists ipsapirone, gepirone and PAPP resulted in significant dose-dependent increases in receptive field (RF) area for withdrawal reflexes when compared to predrug baseline values, indicating an increase in nociceptive sensitivity. The average overall percent maximal increase in RF area following administration of 5-HT1A selective compounds was: 80 +/- 16% for the ventroflexion reflex, 90 +/- 6% for the dorsiflexion reflex and 87 +/- 8% for the lateral flexion reflex. Similar to the effects noted with 5 HT1A agonists, administration of 5-HT1B agonists RU24969, mCPP and TFMPP resulted in a hyperalgesic response with an overall percent maximal increase of 43 +/- 6% for the ventroflexion reflex, 51 +/- 6% for the dorsiflexion reflex and 38 +/- 9% for the lateral flexion reflex. In the tail-flick analgesiometric test, administration of the 5-HT1A agonists 8-OH-DPAT and ipsapirone and the 5-HT1B agonists RU24969 and mCPP resulted in a significant dose-dependent increase in tail-flick latencies when compared to predrug baseline values, indicating a decrease in nociceptive sensitivity to noxious thermal stimuli. No differences in magnitude of the effect of the two receptor subtypes were found, indicating that stimulation of either 5-HT1A or 5-HT1B receptors was equipotent in producing the antinociceptive tail-flick response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410131 TI - Interaction of sigma and PCP-like drugs on operant behaviors in the rat. AB - Many PCP-like drugs interact with at least two types of binding sites in the CNS, one of which is linked to excitatory amino acid transmission and the other with an unknown function. The present experiments were designed to further clarify the mechanism of action of drugs in this class. Assessment was made of the effects of PCP, MK-801, (+)-pentazocine, (+)- and (-)-N-allyl-normetazocine (NANM), (+) amphetamine and BMY-14802 in rats responding under a multiple timeout 600 s (TO), differential reinforcement of low rates 10 s (DRL), fixed ratio (FR) 10 schedule of reinforcement. The effects of the PCP-receptor selective drug MK-801 were compared to those of the mixed sigma/PCP drug (+)-NANM after each were combined with doses of (+)-pentazocine, PCP, BMY-14802, and (+)-amphetamine. MK-801 was also tested in combination with (+)-NANM, as was PCP with BMY-14802. When administered alone, MK-801, PCP, (+)-NANM, (+)-pentazocine, and (+)-amphetamine increased rates of responding under the DRL component of the multiple schedule. The drugs tested generally produced decreases in rates of responding under the FR component. (+)-Pentazocine and BMY-14802 did not modify the effects of (+)-NANM or of MK-801. PCP enhanced the effects of MK-801 and (+)-NANM, and (+) amphetamine enhanced the effects of MK-801 but not of (+)-NANM. BMY-14802 attenuated the effects of PCP. Taken together, these data suggest similarities as well as some differences in the pharmacologic activities of MK-801 and (+)-NANM and PCP. PMID- 1410133 TI - Comparative effects of carbamazepine, phenytoin, diazepam and clonazepam on inhibitory avoidance learning in mice. AB - Four antiepileptic drugs were investigated in an inhibitory avoidance task in mice. Following IP administration 30 min prior to training, carbamazepine (32 mg/kg), phenytoin (30-60 mg/kg), diazepam (2-8 mg/kg) and clonazepam (0.125-0.5 mg/kg) impaired retention. When administered 30 min prior to the retention test none of the drugs under investigation affected retention. The drugs did not affect latencies in the hot plate test. This indicates that in the case of pretraining drug administration effects on retention cannot attributed to elevated pain thresholds. Carbamazepine and phenytoin impaired avoidance learning at doses above those which prevent electroshock induced tonic hindlimb convulsions. Diazepam and clonazepam were effective at lower than anticonvulsant doses. The results of the study are relevant to the evaluation of CNS side effects of anti-epileptic drugs in mice. PMID- 1410134 TI - Differential ethanol intake in Tryon maze-bright and Tryon maze-dull rats: implications for the validity of the animal model of selectively bred rats for high ethanol consumption. AB - The search for a genetically based "animal model of alcoholism" has led to the creation of extensive research programs using various combinations of initial ethanol preference screening techniques and breeding methods to yield rodents with primary genetic differences that contribute to high or low ethanol preference. The present experiment examined the ethanol intake of the Tryon rat strain, which were bred for high and low maze learning scores. It was observed that the Tryon Maze Bright rats displayed an unprecedented affinity for ethanol with stable intakes between 12.7 and 13.7 g/kg per day and preference ratios exceeding 0.75 for ethanol concentrations ranging between 15 and 29%. The pattern of ethanol intake of the Tryon Maze Dull rats resembled the ethanol intake pattern of other, non-selectively bred strains of rats, approximately 2-3 g/kg of absolute ethanol at preference ratios between 0.11 and 0.28. The affinity for ethanol observed for the Tryon Maze Bright rats seems to exceed the reported consumption patterns of rat strains specifically bred for high ethanol consumption although the Tryon rats were selectively bred for variables that were seemingly unrelated to ethanol intake. PMID- 1410136 TI - Pharmacological dissociation between the spatial learning deficits produced by morphine and diazepam. AB - This study sought to determine whether the place learning deficits produced by diazepam are a secondary result of opioid release. Rats pretreated with diazepam (3 mg/kg) or morphine (15 mg/kg) were trained in the Morris water maze. Diazepam impaired place learning-slowing acquisition and preventing the formation of a quadrant preference. Morphine also slowed acquisition, but did not prevent place learning, and impaired escape to a visible platform. Flumazenil blocked the deficits produced by diazepam, but not morphine. Naloxone (2 mg/kg) blocked the deficits produced by morphine, but not diazepam. A high dose of naloxone (10 mg/kg) slowed acquisition, and exacerbated the deficit produced by diazepam. These results demonstrate that diazepam interferes with mnemonic processes through endogenous benzodiazepine receptors, independently of opioidergic systems. Further, they suggest that morphine interferes with motivational processes through opioidergic systems, independently of endogenous benzodiazepine systems. PMID- 1410137 TI - Serotonergic function and late luteal phase dysphoric disorder. AB - Thirty-eight subjects who met criteria for the DSM-III-R diagnosis late luteal phase dysphoric disorder (LLPDD) were compared with 18 controls in 5-HT uptake kinetics of the platelets in the premenstrual (day 26) as well as in the postmenstrual phase (day 4) of the cycle. Furthermore, 5-hydroxytryptophan (5 HTP) was administered to LLPDD patients and controls in both phases of the cycle, to investigate pituitary sensitivity for serotonin. Plasma samples for the measurement of cortisol and beta-endorphin were taken before and after oral administration of 200 mg 5-HTP, and considered as an index of pituitary-adrenal function. LLPDD was not associated with a lower platelet 5-HT uptake and content in the premenstrual phase of the cycle, compared with the postmenstrual phase. Patients appeared not to be different from controls in 5-HT uptake kinetics of platelets in the premenstrual phase of the cycle. No main differences were observed between LLPDD patients and controls in their ability to respond with secretion of cortisol and beta-endorphin to 5-HTP stimulation, either in the premenstrual, or in the postmenstrual phase. This observation could not be attributed to differences in 5-HTP metabolism. The findings of the present study do not support a specific role for 5-HT in the pathophysiology LLPDD. PMID- 1410135 TI - Dopamine and endogenous opioid regulation of picrotoxin-induced locomotion in the ventral pallidum after dopamine depletion in the nucleus accumbens. AB - Microinjection of picrotoxin or the mu-opioid agonist, Tyr-D-Ala-Gly-NmePhe-Gly OH (DAMGO), into the ventral pallidum (VP) produces an increase in locomotor activity that is antagonized by dopamine receptor blockade. To investigate the regulation of VP-induced locomotion by the dopaminergic innervation of the nucleus accumbens (NA) and the role of opioid receptors in this regulation, dopamine innervation of the NA was bilaterally lesioned with 6-hydroxydopamine (6 OHDA). The lesions resulted in an 89-97% depletion of tissue dopamine levels in the nucleus accumbens compared with sham-lesioned rats. Dopamine depletion in the NA failed to significantly antagonize picrotoxin or DAMGO injected into the VP. However, the dopamine receptor antagonist, haloperidol (0.1 mg/kg, IP), blocked the picrotoxin-initiated increase in horizontal photocell counts in both sham- and 6-OHDA-lesioned rats. The opioid receptor antagonist, naloxone (1.0 mg/kg, SC), also blocked the picrotoxin-induced locomotion in 6-OHDA-lesioned rats but did not block locomotion in the sham-lesioned rats. At a higher dose (3.0 mg/kg, SC), naloxone blocked picrotoxin-induced locomotion in both sham- and 6-OHDA lesioned rats. These results indicate that although dopamine depletion in the NA does not affect the permissive role of dopamine transmission on locomotion elicited from the VP, it results in an increased sensitivity to enkephalinergic transmission. PMID- 1410138 TI - Differential effects of early stimulation and/or perinatal flumazenil treatment in young Roman low- and high-avoidance rats. AB - The effect of infantile handling-stimulation and/or perinatal flumazenil (3.7 mg/kg/day) administration on exploratory and emotional-related behavior was investigated using Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats. Postnatal handling increased exploration in 30-day-old rats of both psychogenetically selected lines when they were exposed to a hexagonal tunnel maze including an illuminated central arena. Likewise, postnatal stimulation decreased emotional reactivity in both lines of rats, as expressed by increased entry into the central arena, decreased defecation and vocalization frequency, but these effects were more pronounced in the RLA/Verh line. There were interactions between perinatal flumazenil treatment and rat line, indicating that flumazenil enhanced entry into the maze central arena in handled-RLA/Verh rats, whereas a tendency toward the opposite effect was observed in drug-treated and handled-RHA/Verh animals. Thus, the present study emphasizes that the effects of environmental manipulations are partly dependent upon genetic factors, and that pharmacological effects also depend on both genetic and environmentally-induced predisposition. PMID- 1410139 TI - Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats. AB - Systemic administration of dopamine (DA) agonists markedly disrupts sensorimotor gating in rats as measured by prepulse inhibition (PPI) of the acoustic startle response. A qualitatively similar, but quantitatively weaker disruption of PPI follows DA infusion into the nucleus accumbens (NAC). The present study was designed to determine whether forebrain DA terminal fields other than the NAC contribute to the DAergic modulation of PPI. PPI was impaired significantly after infusion of DA (0-40 micrograms) into the NAC or anteromedial striatum, but not after DA infusion into the orbital cortex or posterolateral striatum. DA infusion into the amygdala also disrupted PPI, but this disruption was accompanied by a dose-dependent decrease in startle amplitude. These results suggest that DA overactivity in the both NAC and anteromedial striatum contribute to the gating disruptive effects of systemically administered DA agonists, and that DA overactivity in mesocortical, mesoamygdaloid and "non-limbic" mesostriatal DA systems are not major substrates for a DAergic modulation of PPI. PMID- 1410140 TI - Age-related changes in serotonin 5HT2 receptors on human blood platelets. AB - Serotonin receptors of the 5HT2 type were labeled on platelet membranes using tritiated ketanserin. Blood was collected from the umbilical cord of newborns and venous samples were collected from 6-year-old children as well as junior-high and high school students (ages 13 through 18) to determine age-related changes in receptor binding. Among the ages sampled, the highest levels of 5HT2 receptor binding were found in 6-year-olds. A sharp decline in receptor binding occurred during adolescence, with levels reduced by half between ages 13 and 17. This pattern is similar to the one we have observed in brain 5HT2 receptors postmortem. There were no significant sex differences in 5HT2 receptors on platelets in newborn and young children. A trend towards higher binding in girls appears around the onset of menstruation in teenage girls (age 14 and up). These results demonstrate that platelet 5HT2 receptors can serve as a model for age dependent changes in 5HT2 receptors in the brain. PMID- 1410141 TI - Absence of withdrawal effects of ritanserin following chronic dosing in healthy volunteers. AB - The possible development of withdrawal symptoms following abrupt discontinuation of ritanserin after chronic administration of 10 mg daily for 8 weeks was investigated in a placebo controlled trial in 40 healthy subjects. The study consisted of two phases. In the first phase, under single blind conditions, all subjects received placebo for 2 weeks followed by a single daily dose of ritanserin (10 mg) for 8 weeks. In the second phase, under double blind conditions, subjects were randomised to receive either placebo or to continue on ritanserin (10 mg) for a further 4 weeks. Psychological assessments were performed at the start of and at intervals throughout the study. Levels of anxiety, concentration, quality of sleep and morning vigilance were measured throughout by daily visual analogue scales. No significant changes were detected in any of the measures in the group of subjects who received ritanserin compared to the group who received placebo during the second phase of the study. Ritanserin discontinuation following chronic dosing in healthy volunteers does not appear to be associated with withdrawal symptoms. PMID- 1410142 TI - Effect of m-chlorophenylpiperazine on plasma arginine-vasopressin concentrations in healthy subjects. AB - It has been demonstrated convincingly that ACTH and prolactin release are under the stimulatory control of serotonin (5-hydroxytryptamine, 5HT). Recent animal studies suggest that stimulation of 5HT activity also induces the release of arginine-vasopressin (AVP). More specifically, m-chlorophenylpiperazine (MCPP), a 5HT agonist widely used to examine 5HT receptor responsivity in human subjects, has been found to induce AVP release in rodents. This study examined whether MCPP increased plasma AVP levels in healthy human subjects. MCPP was administered orally to 17 healthy subjects in a placebo-controlled design in doses of 0.25 and 0.5 mg/kg. AVP was measured twice hourly over a 210 min period after administration of capsules. MCPP did not significantly alter AVP levels as compared to placebo. However, female subjects had significantly lower plasma AVP levels than males. Since it has been suggested that MCPP-induced AVP release in animals is due to stimulation of 5HT1c receptors, the fact that MCPP did not induce the release of AVP in humans suggests that either MCPP is not a potent 5HT1c agonist or that AVP is not released by stimulation of 5HT(1c) receptors in human subjects. The observation of gender differences in plasma AVP levels suggests that this factor should be taken into account in future studies of AVP secretion in plasma. PMID- 1410143 TI - Central versus peripheral effects of muscarinic antagonists: the limitations of quaternary ammonium derivatives. PMID- 1410144 TI - Tolerance to nicotine following chronic treatment by injections: a potential role for corticosterone. AB - C57BL/6 male mice were injected intraperitoneally with nicotine (2.0 mg/kg) or saline three times each day (0800 h, 1300 h and 1800 h) for a period of 12 days and then tested for nicotine tolerance using a series of behavioral and physiological tests. For each of these tests, animals that received chronic nicotine treatment were significantly less sensitive to nicotine challenge than were animals that received chronic saline treatment, as indicated by shifts to the right of dose-response curves. Animals were retested for nicotine sensitivity 2 weeks following cessation of chronic nicotine injections. Tolerance to acute nicotine challenge persisted in nicotine-treated animals. Chronic nicotine treatment by injections did not alter the binding of L-[3H]-nicotine or alpha [125I]-bungarotoxin in any of eight brain regions. Plasma corticosterone (CCS) levels were determined in animals prior to the initiation of the injection series (day 0), and on days 4, 8 and 12 of chronic treatment, immediately before the first injection of the day. CCS levels in nicotine-treated animals were elevated as compared to saline-injected controls by day 12 of treatment. Nicotine-treated animals also had elevated CCS levels 2 weeks after the last chronic injection. Nicotine-treated animals were, however, tolerant to nicotine-induced CCS release. Since previous studies from our laboratory have demonstrated that plasma CCS levels are inversely correlated with sensitivity to nicotine, it is possible that the tolerance to nicotine measured following chronic treatment by injections is due, at least in part, to the elevation in plasma CCS levels. PMID- 1410145 TI - The acoustic startle response as a measure of behavioral dependence in rats. AB - A series of experiments was conducted to assess the sensitivity of the acoustic startle response to chronic morphine administration and naloxone-precipitated withdrawal. Rats were implanted with two subcutaneous pellets containing either 75 mg each of morphine or containing only placebo. In experiment 1, withdrawal induced by 0.05-0.2 mg/kg naloxone dose-dependently decreased the magnitude of the startle response. Physical dependence was confirmed by a naloxone-induced acute weight loss seen in morphine-implanted rats, but naloxone had no effect on startle or body weight in non-dependent animals. In experiment 2, a modified procedure with fewer trials per session and fewer test days was employed. Naloxone (0.2 mg/kg) given 4-5 days after implantation induced large startle response decreases in morphine-dependent rats while having no effect in placebo implanted rats. Post-naloxone saline tests revealed no significant differences in startle between morphine and placebo groups. Startle scores were significantly higher in morphine-implanted rats than in placebo rats during a saline test given 3 days following pellet implantation. In a separate group of animals, however, acute IP injections of morphine from 0.3-10 mg/kg had no significant effect on startle amplitude. The effect of repeated pairings of withdrawal with the startle environment was assessed in experiment 3. Morphine-dependent rats startled significantly less if naloxone injections were given before the startle session than if they were administered 4 h later. Conditioned withdrawal effects, expressed during a final test session when all rats received saline, were observed for the body-weight measure but not for the startle response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410146 TI - Caffeine tolerance and choice in humans. AB - Thirty-two healthy subjects with histories of moderate caffeine consumption abstained from dietary caffeine throughout the study. Subjects were stratified into two groups based on several factors including caffeine preference, which was assessed using a caffeine versus placebo choice procedure. Subsequently, subjects received either caffeine (300 mg t.i.d.) or placebo (placebo t.i.d.) for 18 consecutive days, and thereafter were exposed again to a caffeine versus placebo choice procedure. The study documented tolerance development to the subjective effects of caffeine: after chronic dosing, administration of caffeine produced significant subjective effects in the chronic placebo group but not in the chronic caffeine group. The study also provided indirect evidence for tolerance development: during chronic dosing, the chronic caffeine and placebo groups did not differ meaningfully on ratings of mood and subjective effect. When subjects were categorized into caffeine choosers or nonchoosers, caffeine choosers tended to report positive subjective effects of caffeine and negative subjective effects of placebo. Nonchoosers, in contrast, tended to report negative subjective effects of caffeine. Chronic caffeine did not alter the reinforcing effects of caffeine as assessed by caffeine versus placebo choice, possibly because the relatively short duration of caffeine abstinence in the placebo condition was not sufficient to result in maximal withdrawal effects after termination of the relatively high caffeine dose. This study provides the clearest evidence to date of complete tolerance development to a CNS effect of caffeine in humans. PMID- 1410147 TI - Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans. AB - The effects of depletion of the serotonin precursor, L-tryptophan, on the threshold and tolerance to cold pressor pain, and the analgesic effect of morphine (10 mg intramuscularly), were tested in a double blind trial on human volunteers. Effects on mood were also assessed using the Profile of Mood States and the Addiction Research Center Inventory (ARCI) Scales. To deplete tryptophan, subjects were fed a tryptophan-deficient amino acid mixture 4.5 h before morphine was administered. Controls received the mixture with tryptophan, which is equivalent to a nutritionally balanced protein. The tryptophan-deficient meal reduced plasma tryptophan more than 70% but had no effect on threshold or tolerance to cold pressor pain. After morphine, tolerance to cold pressor pain increased in controls. Tryptophan depletion abolished this analgesic effect. Pain threshold was not altered by morphine. In subjects with normal tryptophan, the analgesic effect of morphine was predicted by the level of plasma morphine-6 glucuronide, but not by the level of morphine. Morphine increased scores on the LSD scale of the ARCI, but had no effect on other measures of mood. Tryptophan depletion also failed to alter mood in these subjects, who had unusually low depression scores before tryptophan depletion. PMID- 1410148 TI - Rebound insomnia in normals and patients with insomnia after abrupt and tapered discontinuation. AB - Rebound insomnia was studied in subjects, aged 25-50 years, with insomnia complaints and normal sleep, insomnia complaints and disturbed sleep, and normal sleep with no complaints (N = 21, n = 7 per group). Standard sleep recordings were collected on a baseline night and after abrupt discontinuation of 6 nights of 0.50 mg triazolam, tapered discontinuation (3 nights of 0.50 mg, 2 nights of 0.25 mg, and 1 night of 0.125 mg triazolam) and 6 nights of placebo. Significantly disturbed sleep on the discontinuation night compared to the baseline night was found. The relative degree of rebound insomnia was greater in the abrupt condition than in either the tapered or placebo conditions. The tapered condition reduced sleep time by half that of the abrupt condition which was twice the reduction found in the placebo condition. An overall (regardless of group or condition) difference in baseline versus discontinuation sleep was found, suggesting that pill discontinuation itself leads to sleep disturbance. Subjects did not differ in rebound insomnia as a function of pre-existing sleep disturbance. PMID- 1410149 TI - Reinstatement of heroin self-administration habits: morphine prompts and naltrexone discourages renewed responding after extinction. AB - The effects of morphine, naltrexone, and nalorphine were studied in rats trained to lever-press for intravenous heroin and then tested under conditions of non reinforcement. Animals were reinforced for lever-pressing on a continuous reinforcement schedule (100 micrograms/kg per infusion) for 2-3 h each day following which reinforcement was terminated and animals were studied under extinction conditions for the remainder of the session. Each day following the termination of responding under extinction conditions, animals were given a single injection of saline, morphine, nalorphine, or naltrexone; lever-pressing under the extinction conditions was then observed for several hours. When animals adapted to this regimen, very low levels of responding were seen following saline injections; morphine (2 or 10 mg/kg) reinstated vigorous responding that lasted 1 4 h. Naltrexone (2 mg/kg) suppressed responding below the levels seen after saline, and nalorphine (10 mg/kg) had the same effect as saline. These observations support the view that opioid-seeking behavior is primed by the proponent or opioid-like actions of opioids and not by the opponent or drug opposite effects associated with opioid withdrawal. PMID- 1410151 TI - Nicotine issues. AB - This issue has covered most of the important concerns of nicotine researchers. Inevitably, there are gaps, because the selection of papers could only cover those which had been submitted or were known to be in preparation and about to be submitted. Nevertheless, these articles should serve to stimulate further discussion of and investigation into all aspects of nicotine use. PMID- 1410150 TI - Serotonergic function during lithium augmentation of refractory depression. AB - Serotonergic mechanisms have been implicated in the pathophysiology of depression and in the neuropharmacology of antidepressant treatment. One measure of central serotonergic function is the prolactin (PRL) response to IV L-tryptophan (L-TRP). We used the L-TRP test to assess the role of serotonin in the mechanism of action of lithium augmentation in refractory major depression. Twenty-six patients with antidepressant-refractory major depression each received three L-TRP tests (after 2 weeks of placebo, after 4 weeks of active primary antidepressant, and after 1 week of lithium augmentation). Primary antidepressant treatment did not increase the PRL response, but lithium augmentation resulted in a statistically significant increase in PRL response as compared to both placebo pretreatment (P less than 0.04) and antidepressant treatment alone (P less than 0.025). This study supports a role for serotonergic mechanisms in the action of lithium augmentation. PMID- 1410152 TI - The role of nicotine in tobacco use. AB - The 1988 US Surgeon General's Report titled "Nicotine Addiction", is cited frequently in the literature as having established the "fact" that nicotine derived from cigarette smoke is addictive in the same sense as "classic" addicting drugs such as heroin and cocaine. This manuscripts critically evaluates key research findings used in support of this claim and identifies shortcomings in the data that seriously question the logic of labeling nicotine as "addictive". In addition, the manuscript argues that the role of nicotine in tobacco use is not like the role of cocaine in coca leaf use as argued by the 1988 Surgeon General's Report, but is, in fact, more like the role of caffeine in coffee drinking as concluded in the 1964 US Surgeon General's Report. PMID- 1410153 TI - Nicotine addiction: a re-analysis of the arguments. AB - This paper evaluates the arguments put forward by Robinson and Pritchard (R&P, this volume) that the conclusions of the US Surgeon General (USDHHS 1988) that nicotine is addictive were ill founded. R&P state that nicotine does not cause intoxication, that many smokers do not exhibit compulsive use, that nicotine is not a euphoriant, that nicotine is a weak reinforcer in other species, that non pharmacological aspects of smoking are important and that negative affect control accounts for more of the variance in questionnaire measures of smoking motives than does habit. This paper points out that intoxication and a euphoriant effect are not normally considered to be central to dependence potential, that no addictive drug results in compulsive use in all users in all situations, that animals do reliably self-administer nicotine, that evidence concerning the apparent importance of non-pharmacological components of smoking do not diminish the importance of pharmacological aspects and that "variance accounted for" of self-report measures of smoking motivation do not bear on the issue of the importance of those motives. The paper concludes with a summary of the essence of the argument that cigarettes are addictive and that nicotine is the primary focus of that addiction. PMID- 1410154 TI - Psychomotor performance in smokers following single and repeated doses of nicotine gum. AB - The psychomotor effects of single and repeated doses of 2 mg nicotine gum were investigated in 13 regular smokers who had abstained from tobacco overnight. In comparison to baseline, a first dose of nicotine led to significantly raised critical flicker fusion thresholds, faster motor reaction times, improved compensatory tracking performance, and faster short-term memory reaction times. Performance after a second and third dose of nicotine remained significantly improved on all measures in comparison to baseline, and absolutely improved when comparing first and third nicotine doses on measures of sensorimotor performance. Throughout, comparisons with a placebo gum condition confirmed that these effects were genuine and not subject to the development of acute nicotine tolerance, suggesting that the enhancement of psychomotor performance experienced by smokers after a first cigarette may be maintained by repeated smoking. PMID- 1410155 TI - Enhancement of continuous performance task reaction time by smoking in non deprived smokers. AB - In a test of the withdrawal-deficit hypothesis of the cognitive effects of cigarette smoking, non-deprived smokers participated in two sessions held on consecutive days. In both sessions, subjects performed two 20-min continuous performance tasks (CPTs). The CPT was a relatively "easy" version designed to require minimal practice (digit 0 target response; digits 1-9 nontarget response; 19% of stimuli targets). In one session, subjects smoked a cigarette prior to each CPT; in the other session they did not smoke (session order counterbalanced). Reaction time (RT) was significantly faster in the smoking session than in the non-smoking session with no difference in number of incorrect responses, a finding incompatible with the withdrawal-deficit hypothesis. Further, light inhalers (as assessed by pre-smoking to post-task increase in expired air carbon monoxide) appeared to process nontarget stimuli faster than deep inhalers, especially in the no smoking session. The results also indicated that, at least during the first CPT of each session, the performance of females in the no smoking session was poorer than in the smoking session and poorer than males regardless of session. In the latter part of the first CPT, the performance of males in the smoking session was better than their performance in the no smoking session. No clear pattern emerged for the second CPT. PMID- 1410156 TI - A comparison of the attentional and consolidation hypotheses for the facilitation of memory by nicotine. AB - Studies examining facilitation of human memory by the administration of nicotine have given equivocal results and it has been argued that the positive findings on memory may have resulted indirectly from an effect on attention, rather than from a direct effect on memory storage. This study compared the "attentional" and the "mnemonic" hypotheses directly, by using both immediate and delayed recall tasks in a verbal free recall study, in which volunteers smoked on a fixed regime during presentation of a 32 word list (namely, one puff after each of eight 4 word blocks). The serial position curve for immediate recall demonstrated a significant improvement on the later blocks of the list (an attentional effect) when volunteers smoked a nicotine-containing cigarette. However, improved performance was found for items at the beginning of the list on the delayed recall measure and this improvement was significant on the first block of 4 words. Since nicotine input had been taken after presentation of this information, the results demonstrate post-learning facilitation of memory by nicotine. PMID- 1410158 TI - Facilitation of memory by post-trial administration of nicotine: evidence for an attentional explanation. AB - In human studies, reported performance improvements with post-trial administration of nicotine have all involved associative learning (Mangan and Golding 1983; Colrain et al. 1992; Warburton et al. 1992). In this study, post trial nicotine, obtained through smoking a cigarette, improved free recall of lists of unrelated words under conditions which limited the opportunity for associative learning. However, the nicotine-induced advantage was not observed when volunteers were required to complete a secondary (attention) task during the post-trial period in which they smoked. The results suggest that post-trial effects depend on the opportunity for stimulus processing after input, and that nicotine improves performance by increasing the attentional resources available for such strategic processing. PMID- 1410157 TI - Effects of post-learning smoking on memory consolidation. AB - The effects of immediate post-learning smoking of low and medium nicotine delivery cigarettes were compared to those of smoking a denicotinised cigarette and a no-smoking control condition in a paired-associate learning task. Thirty nine male smokers were tested for retention of the memorised material at 1 week post-learning. All subjects received all conditions in a repeated measures design. The low nicotine condition was associated with significantly fewer errors on first trial of recall and fewer total errors to criterion. There were no differences in performance reported between the no-smoking and zero nicotine conditions. The medium nicotine condition produced results part way between the no-smoking and low nicotine conditions. Results are discussed in terms of the effects of nicotine on long-term consolidation mechanisms. PMID- 1410159 TI - Function of cigarette smoking in relation to examinations. AB - Eighty-two college students took part in a study on motives underlying increases in cigarette smoking prior to examinations. One group was tested a month before, and a second group was tested the day before, the start of examinations. Measures were taken of current cigarette consumption, general anxiety, anxiety about forthcoming exams, the importance of sedative and stimulant smoking motives, hours spent revising and in other activities and amounts smoked during these activities. The results indicated that the students increased the hours they spent revising and there was a corresponding increase in the number of cigarettes smoked during this activity. They also reported an increase in the importance of stimulant smoking motives. Anxiety levels increased in the run up to exams but there was no increase in sedative smoking motives. The results raise the issue of whether any anxiolytic action of nicotine may be limited to acute stressors and also whether smokers' use of cigarettes to help them stay alert during revision translates into improved examination performance. PMID- 1410160 TI - Euphoriant effects of nicotine in smokers. AB - Two studies were conducted to replicate and extend previous demonstrations of smoking-induced, dose-related reports of euphoria, and to confirm this relationship using measures of plasma nicotine. In experiment 1, overnight deprived subjects, in three different sessions, smoked ultralow-, high-nicotine, and usual-brand cigarettes. In experiment 2, ultralow-, medium-, and high nicotine cigarettes were used, and plasma nicotine was measured. In both studies, subjects were asked to depress a button during euphoric sensations. Number of sensations for the ultralow-nicotine cigarette was significantly lower than for the high-nicotine cigarette in the first study, and than for both the medium- and high-nicotine conditions in the second; a significant linear trend was observed for number of sensations as a function of plasma nicotine level in the second study. For the high-nicotine cigarette, 19 of 22 subjects experienced at least one sensation (mean around three), starting around 2.5 min after lighting up. Together, these studies support the existence of a dose-response relationship for nicotine-induced euphoric sensations; suggest that they are more pronounced following overnight abstinence than following minimal deprivation, and in more dependent smokers; and characterize in detail the temporal features of these sensations. PMID- 1410161 TI - Psychopharmacological effects of smoking a cigarette with typical "tar" and carbon monoxide yields but minimal nicotine. AB - Five male smokers were tested, after 48-h abstention from tobacco-product use, smoking a leading "lights" category cigarette (Control-FTC nicotine yield 0.6 mg) and another cigarette yielding similar amounts of "tar" and carbon monoxide (CO), but only 0.06 mg nicotine (Test). Heart rate (HR) and the electroencephalogram (EEG) were monitored before, during and after the smoking of each cigarette. Other measures obtained included the subjects' puffing and breathing behaviors during smoking, plasma nicotine concentrations, blood carboxyhemoglobin concentrations and expired-air CO. The results indicated no significant differences in the way the subjects puffed and inhaled the two cigarettes and they were therefore assumed to have inhaled similar amounts of particulate matter and gas-phase components. Plasma nicotine concentrations were significantly higher following smoking of the Control cigarette. HR (percent relative change) increased following smoking of either cigarette; however, HR increase was significantly greater following smoking of the Control cigarette. Smoking the Test cigarette had no effect on the EEG. Smoking the Control cigarette produced a significant increase in beta 2 magnitude and a significant decrease in delta magnitude. This indicates that the effects of smoking on the EEG are a function of nicotine absorbed from cigarette smoke upon inhalation and not a function of inhaled particulate matter, CO, or other gas-phase components. PMID- 1410162 TI - Smoking, nicotine dose and the lateralisation of electrocortical activity. AB - The effects of cigarette smoking on the balance of activity of the cerebral hemispheres were studied in two experiments. Experiment 1 examined the effects of smoking on lateralisation of EEG alpha and beta power in six male smokers, and revealed a dose-related biphasic action. Low doses of nicotine as measured by residual butt analysis increased left hemisphere activity in a dose related manner, while higher doses (greater than 1.1 mg) reversed this effect. Experiment 2 examined the time course of the changes in EEG alpha, beta, theta and delta lateralisation in 11 male smokers. During the initial period of smoking there was a reduction in EEG alpha, reflecting cortical activation, followed by an increased in alpha power towards the end of the cigarette. These changes were accompanied in smokers taking moderate nicotine doses, by an initial shift towards left hemisphere activation, followed by a reduction in left hemisphere activation relative to the right. Initial changes in delta and theta power were negatively correlated with nicotine dose. Higher nicotine doses were associated with greater shifts towards right hemisphere activation, as indicated by beta and delta lateralisation, and also with greater decreases in subjective arousal. These results were interpreted as supporting the hypothesis that the stimulant action of lower doses of nicotine involves the activation of a left hemisphere "Go" system, while the sedative effect of higher doses involves increased activation of the right hemisphere "NoGo" system. PMID- 1410163 TI - Acute nicotinic blockade produces cognitive impairment in normal humans. AB - Single oral doses of the central and peripheral nicotinic antagonist mecamylamine were administered to healthy young normal males in doses of 5, 10, and 20 mg in a placebo-controlled, double-blind study. The 20 mg dose caused a significant increase in errors in the learning condition of the Repeated Acquisition task, producing a slower acquisition curve. The lower doses produced less errors, but more than in the placebo condition. There was no effect of drug on the performance component (retrieval of previously learned information). On the recognition memory task, dose-related increases in false-alarms during the delay period were seen, with little effect on misses or hits. Reaction time measures suggested a dose-related slowing of RT on several tasks. Behavioral effects were minimal and physiologic measures were consistent with dose-related ganglionic blockade. We interpret these results to indicate that acute blockade of nicotinic receptor function can produce measurable and significant cognitive impairment, even in non-smoking normals. PMID- 1410164 TI - Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in Alzheimer's disease. AB - This single-blind, placebo controlled study reports on the effects of administering three acute doses of nicotine (0.4, 0.6 and 0.8 mg) subcutaneously to a group of Alzheimer's disease (DAT) patients (n = 22), young adult controls (n = 24), and normal aged controls (n = 24). The study extends our previous findings obtained using smaller groups of subjects. Drug effects were examined on three computerised tests: the first measuring rapid visual information processing, sustained visual attention and reaction time (RVIP task); a delayed response matching to location-order task measuring sustained visual attention and visual short-term memory (DRMLO task); and a finger tapping test measuring simple reaction time (FT task). The critical flicker fusion test (CFF) was used as a measure of perception and the WAIS digit span forwards (DS), of auditory short term memory. Tests were graded in difficulty, titrated to avoid floor and ceiling effects so that meaningful, direct comparisons between groups could be made. Nicotine significantly improved sustained visual attention (in both RVIP and DRMLO tasks), reaction time (in both FT and RVIP tasks), and perception (CFF task -both ascending and descending thresholds). Nicotine administration did not improve auditory and visual short-term memory. There were no consistent, overall patterns of difference in performance between smokers and non-smokers in the control groups, or between males and females in any group. Despite the absence of change in memory functioning, these results demonstrate that DAT patients have significant perceptual and visual attentional deficits which are improved by nicotine administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410165 TI - Experimental model of smoking re-exposure: effects on relapse. AB - This study used a short-term laboratory model of smoking cessation and relapse to prospectively examine the effects of programmed self-administered smoking re exposure during early abstinence. Sixty-seven subjects who had quit smoking for 3 days were randomly assigned either to smoke five cigarettes in their natural environment or to remain abstinent during the exposure period. The main hypothesis, that relapse to regular smoking would be quicker and more prevalent in exposed subjects, was supported. All exposed subjects had relapsed by 2 days post-exposure while 16% of unexposed subjects remained continuously abstinent throughout the 8 day study. This behavioral effect was seen in spite of acute decreases in reported desire to smoke and increases in guilt measured just after exposure. The study supports a role for stimulus re-exposure effects in the relapse process and suggests that additional research on experimental re-exposure is warranted. PMID- 1410166 TI - Use of phenylpropanolamine to reduce nicotine cessation induced weight gain in rats. AB - The present study was conducted to determine if phenylpropanolamine (PPA) administered during the first week of nicotine termination could reduce or eliminate the body weight rebound which accompanies nicotine cessation. Sprague Dawley rats were administered nicotine for 2 weeks after which they received either PPA or saline for 1 week. Control animals received saline during both drug periods. Body weight, food consumption, and water consumption were measured daily before drug, during nicotine and PPA administration, and for 14 days after PPA administration. In contrast to animals receiving saline upon termination of nicotine, animals receiving PPA did not gain weight at an accelerated rate. Termination of PPA did not result in a body weight rebound. To the extent that these results generalize to humans, they suggest that PPA could be used to reduce or eliminate postcessation weight gain in smokers who stop smoking. PMID- 1410168 TI - Nasal nicotine spray: a rapid nicotine delivery system. AB - Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed. PMID- 1410167 TI - Nicotine intake and dependence in Swedish snuff takers. AB - Two studies examining nicotine intake in users of Swedish moist oral snuff are reported. Absorption form a single pinch (2 g) in ten users after overnight abstinence was fairly rapid. The increment in plasma nicotine concentrations averaged 9.9 ng/ml (SD 6.5) after 10 min and peaked at 14.5 ng/ml (SD 4.6) shortly after discarding at 30 min. Among groups of habitual snuff takers (n = 27) and cigarette smokers (n = 35) studied on a day of normal snuffing/smoking, peak blood nicotine levels after use were similar [averaging 36.6 ng/ml (SD 14.4) and 36.7 ng/ml (SD 16.1), respectively], but there was a tendency to higher cotinine levels in the snuffers (399.2 ng/ml versus 306.3 ng/ml). The snuff takers and cigarette smokers reported similar levels of subjective dependence on tobacco. Epidemiological study of Swedish snuff users could clarify whether the cardiovascular risks of tobacco are attributable to nicotine or to other smoke components, as in their case nicotine intake is not accompanied by combustion products. PMID- 1410169 TI - Controlled dosing of nicotine via an Intranasal Nicotine Aerosol Delivery Device (INADD). AB - The present report describes an Intranasal Nicotine Aerosol Delivery Device (INADD) employing an artist's airbrush as aerosolizer and precise, electromechanical control of spray duration. It was designed for the administration of controlled doses of nicotine in a laboratory setting and has been used successfully in over 30 smokers and nonsmokers of both genders. In the present study, nicotine was administered to 12 male smokers at three different doses (0.05 mg, 1.00 mg, and 2.00 mg), and at the same dose (1 mg) on three different occasions. The low dose produced a minimal change in plasma nicotine, while the high dose produced a peak increment of around 16 ng/ml. The medium dose reliably produced a peak increment of around 8-9 ng/ml on all three occasions. Nicotine in plasma showed a sharp rise followed by a slower decline, mimicking the pattern associated with cigarette smoking. Physiological and biochemical responses showed significant dose-response relationships. Subjective reports suggested that aerosol dosing was somewhat aversive, but it is unclear whether this effect is intrinsic to the method or due to other factors. The device described in this report answers the need for a safe and easy means of controlling nicotine dose. Moreover, since nicotine administration via aerosol is novel for both smokers and non-smokers, minimizing the contributions of behavioral tolerance and habituation to the dosing vehicle, it lends itself to the comparison of the pharmacological effects of nicotine between experienced and naive subjects. PMID- 1410170 TI - Is it important that the mind is in a body? Inhibition and the heart. AB - The hypothesis is advanced that certain inhibitory processes necessarily involve autonomic adjustments. Such adjustments would represent a constraint on information processing imposed by the location of the mind in a body. Evidence is reviewed showing that motoric inhibition is related to a transient delay in heartbeat generation. The delay is shown to further depend upon when inhibition occurs in the cardiac cycle. It is argued that this form of interaction between central and autonomic nervous system processing may be common. Central nervous system processes that may control inhibition and integrate information processing with motoric and autonomic processes are discussed. PMID- 1410171 TI - Myocardial and peripheral vascular responses to behavioral challenges and their stability in black and white Americans. AB - The purpose of this study was to assess the short term stability of myocardial and peripheral vascular responses to behavioral challenges, and to compare the response patterns of Black and White men. Blood pressure and heart rate, as well as stroke volume, cardiac output, total peripheral resistance, and systolic time interval measures derived from the impedance cardiogram were obtained in 12 Black and 12 White men. These measures were taken prior to and during an evaluative speech stressor, a mirror star tracing task, and a forehead cold pressor test presented during two laboratory sessions scheduled two weeks apart. In general, total peripheral resistance and impedance-derived baseline measures showed acceptable reproducibility (G greater than .85). With a few exceptions, adequate reliability was also demonstrated for change (delta) scores. All tasks raised blood pressure responses above resting levels. Blacks demonstrated significantly greater increases in total peripheral resistance responses across tasks. Whites but not Blacks also revealed increases above baseline in cardiac output and contractility as estimated by the Heather Index. These findings are consistent with the view that Blacks show greater vascular responsiveness than Whites across a variety of tasks, but reveal less myocardial responsiveness. PMID- 1410172 TI - Mismatch detection and the latency of temporal judgements. AB - Event-related potentials were recorded in two auditory tasks involving the discrimination of pitch or duration of binaurally presented tones. Frequently presented nontarget tones, when compared to the same tones in a simple reaction time task, elicited two negative peaks, NA1 and NA2, followed by a positive peak, nontarget positivity. Infrequently-presented target tones, when compared to the nontargets, elicited mismatch negativity (MMN), followed by N2 and P3b. The peak latencies of NA1 and NA2 did not differ between the pitch and duration tasks, but the duration of NA1 and the peak latencies of mismatch negativity, N2, and P3b, as well as reaction time, increased in parallel for the duration task. It is proposed that the NA1-nontarget positivity sequence reflects the initiation, maintenance, and termination of an attention-modulated process, which is required for the performance of an auditory discrimination task, and that the MMN-N2-P3b sequence reflects a process elicited by infrequently-presented targets, which is the main determinant of reaction time under these testing conditions. PMID- 1410173 TI - The chronometry of attention-modulated processing and automatic mismatch detection. AB - Event-related potentials were recorded from normal subjects in an auditory selective attention task. Targets were rare longer (170-ms) tones of a designated pitch, embedded in a sequence of 100-ms standard tones. The effects of attention modulated processing were evident in the event-related potentials elicited by the standards. Those to relevant standards were similar for easy (1000 Hz vs. 2000 Hz) and hard (1000 Hz vs. 1030 Hz) pitch separations, and were more negative frontocentrally than those to irrelevant standards. Difference waveforms (attended minus unattended standards) revealed Nd, a negative deflection that was earlier in latency for the easy task (onset, 120 ms; peak, 250 ms) than for the hard task (onset, 250 ms; peak, 350 ms). The speed of detection of the deviant longer tones was insensitive to the attention-modulated processes indexed by Nd. Median reaction time did not differ between tasks, although there were more misses and false alarms in the hard task (and nearly all of the latter were to the irrelevant longer tones). Neither direction of attention nor task difficulty affected the latency of mismatch negativity, N2, or P3 (as identified in difference waveforms: attended or unattended longer tones minus their respective standards). The data suggest that performance was guided by two independent but converging processes, automatic mismatch detection of the longer tone and attention-modulated processing of pitch, followed by selection of response. PMID- 1410174 TI - Blushing as a function of audience size. AB - Almost no experimental analysis of blushing has been done since Darwin's observations in 1872. Forty-eight college women watched a videotape intended to elicit blushing, and a videotape not intended to elicit blushing, but elicit physiological responses. A subject was alone, or with one or four persons present. Blushing, which was measured directly with a photoplethysmograph probe on the cheek, was greater during the blushing than nonblushing stimulation. Blushing increased as audience size increased from one to four, but not from zero to one. Audience size and kind of stimulation interacted statistically. Similar results were obtained with ear coloration, cheek temperature, and skin conductance responses, although confidence levels were lower. Cheek coloration and temperature were significantly correlated during nonblushing stimulation, and the zero and one audience conditions, but not during the four audience condition, when blushing was greatest. These results may be placed within the context of emotional effects of audience size generally, including stuttering and speech disturbance, disruption of learning, and self-reported tension. PMID- 1410175 TI - Prestimulation-induced startle modulation in attention-deficit hyperactivity disorder and nocturnal enuresis. AB - Startle modulation was induced by prestimulation in 43, 6-11 year old boys with attention-deficit hyperactivity disorder (ADHD), 13 of whom were or had been enuretic, 17 age-matched enuretic boys, and 42 age-matched normal boys, using 60 ms and 120-ms prestimulation intervals and a 4000-ms continuous tone. There was a significant multivariate effect of enuresis on startle amplitude modulation. This effect was attributed primarily to the reduction of amplitude inhibition following the 120-ms prestimulation interval regardless of whether or not enuresis was associated with ADHD. There was no effect of ADHD on startle modulation by prestimulation. The inhibition following the 120-ms prestimulation interval in the enuretic boys was reduced to the level of 5-year-old normal children, suggesting a maturational component of the deficient startle inhibition. The neurophysiologic dysfunction underlying the deficient startle inhibition in enuresis, but not ADHD, is discussed in terms of a possible dysfunction of mesopontine reticular mechanisms mediating preattentive processing of signals associated with spinal reflexes involved in urinary bladder control. PMID- 1410176 TI - Symptom-specific psychophysiological responses in chronic pain patients. AB - Symptom-specific psychophysiological responding was assessed in 20 chronic back pain patients, 20 patients suffering from temporomandibular pain and dysfunction, and 20 matched healthy controls. Surface EMG from the lower and upper back, the masseter, and the biceps muscles, and heart rate and skin conductance level were continuously recorded during adaptation, resting baseline, and stressful and neutral imagery phases. Univariate and multivariate analyses of variance were performed on raw data as well as data corrected for autocorrelation. The results showed significantly higher EMG reactivity which was lateralized to the left side at the patients' site of pain but not distal sites. This hyperreactivity was observed only during stressful imagery. The healthy controls displayed a significantly higher response in heart rate, but skin conductance level was not significantly different. The results are interpreted as indicative of idiosyncratic muscular response patterns to personally relevant situations at the site of pain in patients suffering from chronic muscular pain. PMID- 1410177 TI - Respiratory sinus arrhythmia and cardiovascular responses to stress. AB - The parasympathetic nervous system provides mechanisms that could attenuate sympathetically mediated heart rate stress responses and might have even more general antagonistic actions on stress reactivity. Individuals characterized by higher levels of parasympathetic tone might, through such mechanisms, be less reactive when stimuli elicit sympathetically mediated responses. Respiratory sinus arrhythmia (RSA) is considered to be a noninvasive index of cardiac parasympathetic (vagal) tone. The present study investigated whether individual differences in RSA level at rest could predict variations among individuals in the magnitude of cardiovascular responses to psychological stress. None of the measures of resting respiratory sinus arrhythmia, derived from spectral analysis of beat-to-beat changes in resting heart rate, predicted the observed variations in cardiovascular task reactivity. However, scores reflecting respiratory sinus arrhythmia as the percentage of total heart rate variability (RSAnorm) were negatively correlated with blood pressure levels, both at rest and during the task. Furthermore, subjects with higher scores for RSAnorm demonstrated a faster adaptation of heart rate responses during stress, which suggests the development of parasympathetic antagonism to ongoing sympathetic arousal. Although a simple relationship between respiratory sinus arrhythmia and reactivity was not observed, these results encourage further investigation of RSA measures as psychophysiological indices of individual differences in parasympathetic (vagal) cardiac tone, or perhaps of general parasympathetic/sympathetic balance, which could modulate the expression of potentially pathogenic stress responses. PMID- 1410178 TI - Event-related potentials and the identification of deviant visual stimuli. AB - The effects of deviant visual stimuli on event-related potentials were investigated in a counting task (Experiment 1) and in a reaction time task (Experiment 2). In Experiment 2 the interstimulus interval was either short or long (340 vs. 1020 ms). The stimuli (two angles within a frame) were frequent (Standard) or deviant (differing from the Standard either in the orientation of the two angles, or in the thickness of the frame, or in both of these features). In various conditions the target stimuli were defined by one of the deviant features or by the conjunction of these features. Subjects were more accurate in the counting task, and the reaction time was shortest when the target feature was the deviant angle orientation. Performance was lowest for the conjunction of the deviant features. The deviant angle orientation elicited a posterior negative wave in the 140-180 ms range. As the interstimulus interval increased, the magnitude of this component decreased. All stimuli with relevant (attended) deviant features elicited another posterior negative wave in the 180-260 ms range, as well as an anterior positivity with similar latency. When the interstimulus interval was short, and the only target was the Conjunction Deviant, the summed occipital activity to the relevant features of deviant nontarget stimuli was larger than the negativity to the Conjunction Deviant. Target stimuli elicited late positive waves, which were sometimes preceded by central negativity. PMID- 1410179 TI - Recent developments in the study of cardiovascular reactivity: contributions from psychometric theory and social psychology. AB - Two related ongoing research programs are described. The first examines optimal measurement strategies for assessing individual differences in cardiovascular reactivity, and the second investigates the effects of the social environment as a moderator of cardiovascular responding during psychological challenge. Models and evidence from related behavioral sciences (Psychometric Theory and Social Psychology, respectively) have provided useful guidance for this work. Relevant background and current data examining the measurement and determinants of cardiovascular reactivity are reviewed, with a focus on these multidisciplinary contributions. The implications of the work for the construct of reactivity and its possible role as a marker of disease risk are discussed. PMID- 1410180 TI - The identification of concealed memories using the event-related potential and implicit behavioral measures: a methodology for prediction in the face of individual differences. AB - The development and validation of an event-related potential (ERP) memory assessment procedure is detailed. The procedure identifies learned material with high rates of accuracy, whether or not subjects give intentional responses indicating they had previously learned it. Because the traditional analysis of variance approach fails to provide probabilistic conclusions about any given individual, Bayesian posterior probabilities were computed, indicating the probability for each and every person that material was learned. The method was developed on a sample of 20 subjects, and then cross-validated on two additional samples of 20 subjects each. Across the three samples, the method correctly defined over 94% of learned material as learned, and misclassified 4% of the unlearned material. Additionally, in a simple oddball task performed by the same subjects, the method classified rare and frequent material with perfect accuracy. Finally, combining two implicit behavioral measures--mean reaction time and the number of incorrect responses--in Bayesian fashion yielded classification accuracy that actually exceeded that of the ERP-based procedure overall, but the two methods provided identical accuracy in classifying the most critical material as recognized. PMID- 1410181 TI - Event-related potentials and autonomic responses to a change in unattended auditory stimuli. AB - Event-related brain potentials (ERPs) and autonomic nervous system (ANS) responses to occasional pitch and rise-time changes in a task-irrelevant auditory stimulus repeating at short intervals were measured while the subject performed a difficult intellectual task (Raven Matrices). It was found that deviant stimuli elicited the mismatch negativity (MMN) component of the ERP even when they elicited no ANS response. There was no significant difference in the mismatch negativity between trials in which the skin conductance response was or was not elicited. The pitch deviant tone also elicited heart rate deceleration, whereas the rise-time deviant tone tended to elicit a later heart rate acceleration. Neither heart rate change correlated with the mismatch negativity. The pattern of results obtained suggests that the mismatch negativity is generated by an automatic discrimination process associated with the cerebral events initiating the orienting response to stimulus change, but does not necessarily lead to the orienting response elicitation. Longer-latency ERP components tended to show slight covariation with ANS responses. The P3 was larger when a skin conductance response was elicited than when it was not elicited. Further, heart rate change trials tended to be accompanied by larger slow waves than trials with no heart rate response. Heart rate acceleration trials were accompanied by a larger slow parietal positivity and a smaller frontal negativity than were heart rate deceleration trials. PMID- 1410182 TI - The temporal locations of heartbeat sensations. AB - This experiment examined individual differences in the temporal location of heartbeat sensations and the reliability of their detection. Following practice on a familiarization task in judging light-tone simultaneity, 50 subjects were studied for two sessions on a heartbeat detection task, which required judging the simultaneity of heartbeat sensations and tones presented at six intervals following the onset of ventricular contraction. Subjects inspected the heartbeat tone intervals as frequently and for as long as desired before choosing the one in which heartbeat sensations and tones were most simultaneous. The temporal locations of heartbeat sensations in subjects classified as "good heartbeat perceivers" (n = 16) ranged from 131 and 363 ms following ventricular contraction (mean = 228 ms). Correlations between the familiarization and heartbeat detection tasks in the accuracy of simultaneity judgments and in the frequency and duration of interval inspections suggest that general perceptual abilities and strategies may underlie success in detecting heartbeat sensations. PMID- 1410183 TI - Mismatch negativity in event-related potentials to auditory stimuli as a function of varying interstimulus interval. AB - The mismatch negativity, isolated as a component of the event-related brain potential elicited by deviant auditory stimuli, was suggested by Naatanen (1984) as an indirect measure of the inferred neuronal representation of standard stimuli. The purpose of the present study was to determine the duration of the neuronal representation by varying the interstimulus intervals of 1, 6, and 10 seconds within experimental blocks. Mismatch negativities were found to be elicited by deviant stimuli (1500-Hz tones, sequential probability 10%) following standard stimuli (1000-Hz tones) with interstimulus intervals of 1, 6, and 10 s as well. The results suggest a duration of neuronal representation of at least 10 s. The within-block variation of interstimulus interval, the rather low temporal probability of deviants, and their large frequency deviance might explain the present results contradicting earlier findings that suggested a shorter duration of that neuronal representation. PMID- 1410184 TI - Ambulatory monitoring of respiration: inhibitory breathing in the natural environment. AB - Because previous work found that sustained inhibitory breathing (i.e., low frequency breathing without increased tidal volume) can occur in laboratory animals under conditions of behavioral stress, this study sought to determine whether a comparable respiratory pattern could be observed in ambulatory human subjects in their natural environments. Tidal volume, breathing frequency, and minute ventilation were monitored continuously during 24-hour sessions via inductive plethysmography and a portable microprocessor. Mean tidal volume and minute ventilation were significantly higher during the daytime than at night for all subjects. However, mean breathing frequency was not consistently higher during the daytime, because episodes of low frequency breathing offset episodes of high breathing frequency. Tidal volume during low frequency breathing was comparable to that observed during medium or high frequency breathing. Thus, low frequency breathing was indicative of low minute ventilation. The eliciting stimuli, physiological concomitants, and relevance to health of this energetically inefficient breathing pattern remain to be determined. PMID- 1410185 TI - Family history of hypertension and cardiovascular changes during high and low affect provocation. AB - The present study investigated whether subjects with a positive family history of hypertension would display differential responses in blood pressure and heart rate across different laboratory tasks. We also wanted to know whether subjects would display stable within-subject responses across different laboratory tasks. Twenty-three family history positive subjects and 23 with a negative family history participated in three tasks: 1) mental arithmetic, 2) a conversation about the weather (low affect task), and 3) a conversation about a recent upsetting, interpersonal event (high affect task). Positive family history was associated with elevated diastolic resting blood pressure and greater diastolic responsivity overall. For both groups, arithmetic was associated with the greatest heart rate changes, whereas the distressing conversation was accompanied by the greatest diastolic blood pressure response. Stability of cardiovascular activation across different tasks was present only for heart rate; it was weak for diastolic blood pressure, and completely absent for systolic blood pressure. PMID- 1410186 TI - The 24-hour sleep propensity function: experimental bases for somnotypology. AB - The present study investigated the temporal structure of sleep propensity during 48 hours using an ultrashort 7-min sleep/13-min wake cycle. Eight subjects were tested under two experimental conditions of either attempting sleep, or resisting sleep after a monitored night in the laboratory. Electrophysiological recordings were carried out during the 7-min trials. The temporal structure and the overall level of sleepiness of the 48-hour sleep propensity functions calculated from the amount of total sleep in each trial revealed a high within-subjects stability. This was found both across the two days of the study within conditions, and across conditions. Also, diurnal levels of sleepiness were systematically related to nocturnal sleep parameters. Subjects having short nocturnal sleep latencies and higher sleep efficiencies slept more during the day. It is proposed that the structure and level of the sleep propensity function can be used to characterize individuals along two dimensions of somnotypology: "morningness-eveningness" and "sleepy-alert." PMID- 1410187 TI - Psychometric properties of resting anterior EEG asymmetry: temporal stability and internal consistency. AB - We examined whether resting anterior electroencephalographic (EEG) asymmetry in the alpha frequency band has psychometric properties that would be expected of a measure assessing individual differences. In each of two experimental sessions, separated by three weeks, resting EEG in midfrontal and anterior temporal sites was recorded from 85 female adults during eight 60-s baselines. Resting alpha asymmetry demonstrated acceptable test-retest stability and excellent internal consistency reliability. Analyses including other frequency bands indicated that degree of stability varied somewhat as a function of band and region. In addition, asymmetry was less stable than absolute power. Discussion focuses on the implications of the present findings for the measurement and conceptualization of resting anterior asymmetry. PMID- 1410188 TI - A developmental event-related potential study of picture matching in children, adolescents, and young adults: a replication and extension. AB - Event-related potentials were recorded in a developmental study of picture matching using an adaptation of Posner's (1978) letter-matching tasks. Subjects ranging in age from 6-39 were asked to decide whether two line drawings, presented sequentially, were the same or different on the basis of physical (physical identity), nominal (name identity), or categorical (category identity) criteria. The amplitude of a negativity at 400 ms (Neg400) increased as the number of dimensions on which the two line drawings differed increased. This effect held for all age groups, and was interpreted as reflecting the degree of semantic and/or physical relationship between the two pictures. However, one finding for Neg400 did suggest a qualitative difference in processing mode between the younger and older subjects. Both Neg400 and P3b latencies showed highly significant linear age trends, decreasing with increasing age. These age related changes were interpreted as demonstrating quantitative speed of processing differences among age groups. The latencies of both Neg400 and P3b increased as the matching criteria became more complex. Moreover, P3b latency increased as the number of dimensions on which the two pictures differed increased, and this did not interact with age. Although both Neg400 and P3b showed age-related changes in scalp distribution, the fact that each was related to the experimental variables in similar fashion in all age groups suggested that they were homologous components across the age range studied. Taken as a whole, the data support continuity of information processing during these tasks across a wide age range. PMID- 1410189 TI - Posttraumatic stress symptoms in victims of childhood incest. AB - The relationship between posttraumatic stress disorder (PTSD) and the experience of severe childhood incest was investigated in a comparison of 97 adult female victims of incest and 65 matched controls. It appeared that 62% of the incest victims and none of the controls met the DSM-III-R criteria for PTSD. The best predictor for the development of PTSD appeared to be the subjective reaction at the time of the event, consisting of anxiety, freezing and dissociation. The incest victims also displayed other psychiatric symptoms, such as self-mutilation and conversions. Although the relation incest-PTSD is quite obvious, the diagnosis may easily be missed because the symptoms may be masked by other psychiatric phenomena. PMID- 1410190 TI - Father kills mother: post-traumatic stress disorder in the children. AB - Results of a study of over 100 children whose father killed their mother have been summarized and principles for practice have been formulated. All children orphaned by the death of one parent at the other's hands should be seen as soon as possible in a child psychiatry department and assessed. An immediate crisis intervention will probably be needed if they witnessed the killing to prevent PTSD. Bereavement counselling will be helpful in most cases. The caretakers will need support and help with their own mourning. Placement, access and custody, compensation, seeing the body, attending the funeral and dealing with family conflict will all need consideration. Long-term follow-up and further research are recommended. PMID- 1410191 TI - Fluvoxamine treatment for chronic PTSD: a pilot study. AB - A group of 24 Dutch World War II Resistance veterans with a documented traumatic war history and a (partially) positive diagnosis of current posttraumatic stress disorder (PTSD) was studied. This special group of war victims is characterised by chronicity, suffering from intractable posttraumatic complaints for decades. They were treated with fluvoxamine (Fevarin), a selective serotonin reuptake inhibitor with antidepressive and anxiolytic properties. The study was designed as an open-ended, outpatient pilot study, with a treatment period of 12 weeks. Results of clinical examination, and questionnaires investigating PTSD, depression, sleeping problems, anxiety, and vital exhaustion indicate that a significant number of the subjects improved with respect to their PTSD symptomatology, and their symptoms of anxiety and vital exhaustion. However, at the end of the study, quantitative improvement was modest. The results indicate that treatment with fluvoxamine may offer alleviation of chronic PTSD symptoms, in particular insomnia, nightmares, anxiety, intrusive recollections, guilt feelings and tiredness. PMID- 1410192 TI - Current posttraumatic stress disorder and cardiovascular disease risk factors in Dutch Resistance veterans from World War II. AB - The extraordinary trauma experienced by Resistance veterans from World War II (WW II) and other veterans may be associated with an increased incidence of posttraumatic stress disorder (PTSD) and somatic morbidity, including cardiovascular disease (CVD). This study explored some relationships between current PTSD and CVD risk factors in 147 male Dutch WW II Resistance veterans. They were compared to 65 same-aged male patients with a recent myocardial infarction and 79 surgical patients. Of these subjects, WW II Resistance veterans scored highest on CVD risk factors (i.e., angina pectoris, type A behavior, life stressors, and vital exhaustion), except smoking. Fifty-six percent of these veterans were currently suffering from PTSD. They reported CVD risk factors, in particular type A behavior and vital exhaustion, more often than veterans without PTSD; they also reported more premorbid adverse living conditions. These data suggest that early sensitization to environmental stressors may be associated with a high prevalence of current PTSD and excess CVD risk factors in subjects exposed to extraordinary war-time trauma and that this may lead to vital exhaustion. PMID- 1410193 TI - Anxiety, depression and anger in Dutch Resistance veterans from World War II. AB - In this study, 147 Dutch Resistance veterans from WW II are evaluated on psychometric instruments for anxiety, depression and anger. Resistance veterans appeared to be more anxious, depressive and angry on these instruments compared to controls from the validation studies of the respective instruments. Veterans currently suffering from PTSD (56%) were significantly more anxious, depressed, and angry than veterans without PTSD. With respect to staying in Nazi concentration camps, which is an extremely severe stressor, and in which half of the veterans were imprisoned, no difference on the three instruments was found. Anxiety, depression and anger were observed to be highly interrelated in PTSD. The close interrelationship between anxiety and depression, anxiety and danger, and depression and anger mediated by way of anxiety is, however, not unique for traumatized subjects. It is argued that for Resistance veterans only the intrusive reminiscences of the stressful events discriminate this constellation of symptoms from subjects with an anxious-depressive symptomatology. PMID- 1410194 TI - Somatic reenactment in the treatment of posttraumatic stress disorder. AB - Somatic reenactments, like other intrusive symptoms in post-traumatic stress disorder, such as flashbacks and nightmares, reproduce the mental content of traumatic events. Four cases are presented from survivors of military trauma and civilian catastrophes. The patients were part of larger research projects carried out by the University of Cincinnati Traumatic Stress Study Center. Understanding such symptoms as repetitions of the trauma itself proved useful therapeutically, especially in consolidating the working alliance. PMID- 1410195 TI - Swedish UN soldiers in Cyprus, UNFICYP: their psychological and social situation. AB - Two Swedish rifle batallions serving as UN soldiers in Cyprus (UNFICYP) have been investigated with respect to their demographic background and motives for application for UN service. The comparison of symptoms of stress in general, of posttraumatic stress disorder specifically, and some other variables of reaction with various studies of Swedish UN soldiers in different settings has given the following results. Very few interviewees experienced 'personal nervous breakdown' (0.5%). The soldiers reported in general very few psychological or psychosomatic complaints in the short time perspective. There seemed, however, to be two groups of persons at risk, namely those who were repatriated and those with a high consumption of alcohol. PMID- 1410197 TI - Post-traumatic stress disorder in child survivors of shipping disasters: the sinking of the 'Jupiter'. AB - 334 of over 400 children who survived the sinking of the cruise ship, Jupiter, in Athens harbour in October 1988 completed a battery of questionnaires 5-9 months later. Compared with age- and sex-matched controls, they show significantly higher scores on depression and anxiety. They also report more fears, particularly of stimuli related to the trauma. Overall, their scores on the Impact of Events Scale are as high as those reported by adults in other disasters. Follow-up studies a year after the accident reveal that nearly half the children meet the DSM-III-R criteria for PTSD. The usefulness of this screening battery is discussed. Some evidence for the effects of early intervention in schools is presented. PMID- 1410196 TI - Stereotypies in sows during chronic stress. AB - In pig husbandry sows are fixed in such a way that they undergo a chronic loss of control over their environment. In these conditions sows develop stereotypies that are associated with a specific activation of brain endorphins. Stereotyping itself reduces some neuroendocrine stress symptoms. During stress at least two coping styles can be distinguished in many mammals and birds. These types are found again in the stressed sows which either maintain a high or a low level of stereotypies. The low stereotyping sows show the strongest signs of uneasiness. PMID- 1410198 TI - Fellowship training objectives and readings in consultation-liaison transplantation psychiatry. PMID- 1410199 TI - The role of psychological factors in gastrointestinal conditions. A review pertinent to DSM-IV. AB - The authors reviewed the literature to assess the relationship between psychological factors and gastrointestinal conditions. The conditions that were found to be more relevant and worthy of future investigation were nonulcerative dyspepsia, inflammatory bowel disease (regional enteritis), and irritable bowel syndrome. The pertinent findings suggest that an important link exists between psychological factors and gastroenterological disorders, which supports the need for modification of the DSM-III-R's diagnostic category, "Psychological Factors Affecting Physical Condition." In concert with a subcommittee addressing other organ systems and psychological factors, the authors conclude that a diagnostic approach with greater utility would be useful for both researchers and clinicians. A conceptual framework as proposed in DSM-IV could also advance knowledge of psychological factors and their contribution or role in the etiology, perpetuation, and exacerbation of certain gastrointestinal conditions. PMID- 1410200 TI - Ophthalmologic effects of psychotropic medications. AB - This article reviews the effects of psychotropic medications on the eye. Although some of these effects have been known for years, they have been largely ignored by psychiatrists. The ophthalmologic effects of antidepressants, neuroleptics, benzodiazepines, carbamazepine, and lithium in therapeutic doses and overdose are reviewed and their implications discussed. Recommendations are made for appropriate monitoring, treatment, and ophthalmologic referral of patients on these medications. PMID- 1410201 TI - Diagnosis and treatments of hypochondriacal syndromes. AB - There are controversies in the literature about the diagnosis and most appropriate treatment of hypochondriasis. The author offers guidelines for diagnosis of hypochondriacal syndromes that have not been adequately dealt with in the literature and discusses the choice of treatments. PMID- 1410202 TI - Detection of depression in the stroke patient. AB - The literature suggests the hypothesis that nonpsychiatrists will underrecognize depression in evaluations of stroke patients. On a medical rehabilitation ward, 15 stroke patients were evaluated for depression by psychiatric interview and self-report. Charts were examined for detection of depression by the rehabilitation team. The hypothesis was supported: in contrast to psychiatric interview (68% depressed) and self-report (Beck Depression Inventory, 50% depressed), none of the patients were described as depressed in chart notes by the rehabilitation team (excluding the psychiatrists). Psychiatrists should develop ongoing interactions with primary care physicians to improve detection of poststroke depression and other depressions on medical wards. PMID- 1410203 TI - Inpatient treatment of persistent somatization. AB - Patients with disabling, persistent somatization pose significant challenges in clinical management. This study describes 92 patients treated on an inpatient psychosomatic medicine unit for persistent somatization. The most important factor in defining clinically significant subgroups of these patients was mood. Compared with depressed somatizing patients, nondepressed somatizing patients had chronic illnesses of early onset, had symptoms that were not correlated with current life stressors, and were generally unresponsive to treatment. There were few clinical predictors of treatment outcome apart from the duration of symptoms, the presence of mood disturbance, and a history of stable interpersonal relationships. PMID- 1410204 TI - Panic disorder and chest pain in the coronary care unit. AB - Consecutive admissions to a university hospital coronary intensive care unit were prospectively evaluated using a modified version of the Structured Clinical Interview for DSM-III-R by interviewers blind to the patient's cardiac status. Panic disorder was present in almost one-third of the patients. Four (21%) of the 19 patients with panic disorder also had positive cardiac findings, including 2 who had myocardial infarctions. Of the 27 patients with negative cardiac findings, 15 (55.5%) had panic disorder. Whereas panic disorder and coronary heart disease may coexist in patients with acute chest pain, there appears to be a very high prevalence of panic disorder among patients in whom cardiac disease has been excluded. PMID- 1410205 TI - Making a consultation service work. An organizational commentary. PMID- 1410206 TI - Obsessive-compulsive symptoms associated with acute intermittent porphyria. PMID- 1410207 TI - Buspirone-induced psychosis in a human immunodeficiency virus-infected man. PMID- 1410208 TI - Thalamic pain syndrome complicating the evaluation of a patient with poststroke depression. PMID- 1410209 TI - Improvement of arthritis with fluoxetine. PMID- 1410210 TI - Use of amitriptyline in a patient with tinnitus. PMID- 1410211 TI - Organic delusional disorder on a consultation-liaison psychiatry service. Report and review. PMID- 1410212 TI - Pemoline. An alternative psychostimulant for the management of depressive disorders in cancer patients. PMID- 1410213 TI - Pseudocyesis in a schizophrenic woman of child-bearing age. PMID- 1410214 TI - Fluoxetine and depersonalization syndrome. PMID- 1410215 TI - On "Psychotherapy by telephone: a therapeutic tool for cancer patients". PMID- 1410216 TI - Can we finish the war? PMID- 1410217 TI - The Society of Medical Officers of Health: a Scottish centenary. PMID- 1410218 TI - Trends in mortality from stroke in Scotland, 1950-1986. AB - The Scottish Registrar General's Annual Reports have been used to study trends in mortality from stroke in Scotland during 1950-1986 in those aged 45 to 74. In 1950 the age-adjusted mortality rate was 347.4 per 100,000 population for men and 360.8 for women, falling to 199.6 for men and 155.8 for women in 1986. This downward trend has increased from 1976 for males. The average annual decline in age-adjusted mortality from stroke over the 37-year period was 4.0 per 100,000 in males and 5.5 in females. This reduction in death rates was proportionally higher for women compared with men in all age groups over 55 years. As with cardiovascular deaths, mortality from stroke was lower in the east than in the central region and west of Scotland. The reduction in mortality resulted in a substantial 'saving' of lives, estimated at 12,500 between 1980 and 1984. PMID- 1410219 TI - Uses of the accident and emergency department in Scotland: patient characteristics and expectations. PMID- 1410220 TI - General practitioners and public health. AB - Family Health Service Authorities (FHSAs), since 1st April 1991, have been both 'managed', by the Regional Health Authority, and 'managing', their contractor services. Both situations are relatively new to them, their Region and the contractors. We examine the opportunities and potential problems of this major strategic change. These relate to: (1) the establishment of effective coordination between providers of primary care services; (2) the establishment of minimum basic standards of care and administration for GPs (based on those set for training practices by the Regional Advisors in General Practice); (3) the development and validation of a data collection system from General Practice which could be used to establish a morbidity database from general practice as a means of health needs assessment as well as for performance review. PMID- 1410221 TI - Internal variation in the uptake of whooping cough immunisation within a Health Authority. AB - Data were obtained on the vaccination history of 6,898 children immunised with D3, the final dose of diphtheria vaccine. These children were born between 1984 and 1990 and were also resident within a single Health Authority during part or all of this time. Analysis of this data revealed consistent variation by treatment centre in the uptake of whooping cough vaccine in those children receiving the diphtheria vaccine. Certain treatment centres consistently achieved greater success in giving the whooping cough vaccine to those children who had received the diphtheria vaccine. PMID- 1410222 TI - Height, body mass index and mortality: do social factors explain the association? AB - The aim of the study was to analyse the effects on mortality of body height and body mass index (BMI) in young men, taking into account social and behavioural characteristics in early youth. The study is a 20-year follow-up of all Swedish men (n = 50,465) conscripted for military service in 1969-70. Baseline data on body height and weight as well as interview and questionnaire data on social and behavioural characteristics were linked to mortality data up to the end of 1988. Nine hundred and forty-six men died during the follow-up. We found a significant increase in mortality by decreasing body height; persons below 165 cm had an almost twofold increased mortality compared with those of average height. This association was reduced to the limit of statistical significance when we controlled for social and behavioural characteristics in a multivariate model. Persons with a BMI above 30 had a more than twofold increased mortality compared with those of average BMI. This association remained highly significant in a multivariate model. We thus confirmed previous findings of an inverse association between body height and mortality, but found that this association was almost entirely due to social background factors. The independent association between BMI and mortality may indicate a stronger genetic influence on BMI than on body height. PMID- 1410223 TI - Psychological ill-health in Chinese communities in Hong Kong. AB - Psychiatric symptoms are widely distributed in the general population while psychiatric impairment or psychological ill-health is prevalent in many communities, especially those with stressful environments. Data concerning Chinese communities are scanty. The present study employed the use of a General Health Questionnaire to screen the general population for psychological ill health in Hong Kong and the results showed that between 18.3% and 26.3% of Chinese could be considered as probable or potential candidates for mental illness. The authors discuss the significance of these findings. PMID- 1410224 TI - Detection of subclinical ascorbate deficiency in early Parkinson's disease. AB - From mid-October 1989 to mid-July 1990 all newly admitted residents to Bury Local Authority Residential Homes were comprehensively medically screened. In a series of 100 residents eight had early Parkinson's disease (six of them hitherto undiagnosed). Seven showed evidence of Vitamin C deficiency. Of the seven showing evidence of deficiency, four suffered from early Parkinson's disease. Of the 93 without evidence of Vitamin C deficiency only four had Parkinson's disease. This indicates a significantly higher prevalence of Parkinson's disease in the group with Vitamin C deficiency (P less than 0.001 using Fisher's exact). PMID- 1410225 TI - Audit: what's in the name? AB - Medical audit is based on a cyclical model which is ideally suited to operational work that is (1) regularly repeated in similar situations; (2) clearly and directly linked to outcomes; (3) amenable to criteria of quality. The work of public health physicians is both operational (e.g. investigation of outbreaks of communicable disease) and strategic (e.g. health needs assessment). A cyclical model is not appropriate to strategic activity. Evaluation of that activity is essential--but should not be constrained/limited by inappropriate adherence to the audit cycle. PMID- 1410226 TI - Towards a more rational policy for colposcopy. AB - The objective of the study was to establish the relationship between the results of positive and abnormal cervical smears and the corresponding colposcopic biopsy results and its relevance to clinical management. A retrospective analysis of linked results was carried out at the Princess Anne Hospital, Southampton. The main outcome measure was the correspondence between a positive or abnormal cervical smear and the related colposcopic biopsy. Colposcopic biopsies were carried out on 1,841 consecutive women. Of these, 1,424 (77.4%) had moderate or severe dyskaryosis on their smears. Of the 1,767 with definitive results on their smear, 1,101 (62%) showed exact correspondence between the cervical smear and the colposcopic biopsy. Ninety-one (26%) of all women with mildly dyskaryotic smears were reported as showing CIN II or CIN III on biopsy. We conclude that women with moderate or severe changes on cervical smear should not be asked to attend for confirmatory colposcopic biopsy prior to treatment, but those with persistent mild changes should be referred for separate diagnostic colposcopy. PMID- 1410227 TI - Salmonella in tropical freshwater fish 'carriage water'. PMID- 1410228 TI - Food irradiation--promising technology for public health. PMID- 1410229 TI - First year of AIDS services delivery under Title I of the Ryan White CARE Act. AB - This is a review of (a) the emergency assistance for ambulatory HIV medical and support services provided in the first year by eligible metropolitan areas (EMAs) funded under Title I of the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act of 1990, (b) the varied responses and processes by which the 16 urban areas receiving Title I funds in 1991 met legislative mandates, (c) the central nature of planning councils under Title I and their formation and functioning, and (d) issues related to current implementation and future expansion of Title I to additional eligible metropolitan areas. Integral to the review is a brief discussion of the history of AIDS and HIV infection, particularly in cities receiving CARE Act funding, an overview of Title I requirements, and a description of the organizational structures cities are using to implement Title I. Information on Title I EMAs is based on analysis of their 1991 applications, bylaws of their HIV service planning councils, intergovernmental agreements between Title I cities and other political entities, and contracts executed by Title I grantees with providers for the delivery of services. Interviews with personnel in several Title I EMAs, including planning council members and grantee staff members, provided additional information. This is the first descriptive accounting of activities related to the 1991 applications for and uses of Title I funds, and the administrative and service issues related to this process. PMID- 1410230 TI - 15-month followup of women methadone patients taught skills to reduce heterosexual HIV transmission. AB - Heterosexual contact with intravenous drug users accounts for a growing proportion of cases of acquired immunodeficiency syndrome (AIDS) among women. In an earlier study designed to reduce sexual risk behavior, the authors randomly assigned 91 methadone maintained women to information-only or skills-building conditions. Modest outcomes favored participants in the skills-building group. In this 15-month followup of 62 remaining study participants, skills-training group members were more likely than controls to use condoms. In comparison with controls, members in the skills-building group felt more comfortable talking about safe sex, perceived themselves as more able to reduce their exposure to AIDS, but were more likely to attribute AIDS risk to luck. No associations were found between group condition and number of sexual partners or frequency of buying and carrying condoms. Some gains associated with a group intervention tended to be maintained over time, indicating that preventive interventions composed of multiple sessions and conducted in treatment settings may have promise as useful strategies to prevent human immunodeficiency virus (HIV) infection. Nevertheless, decay was evident in other domains, suggesting that prevention specialists should consider booster sessions or other means of maintaining changes in risk behavior. PMID- 1410231 TI - Sexual practices and AIDS knowledge among women partners of HIV-infected hemophiliacs. AB - About 12 percent of the women sex partners of hemophilic men who are seropositive for the human immunodeficiency virus (HIV) have themselves become seropositive. Questionnaires were completed in January 1988 by 15 women who were in long-term, monogamous relationships with HIV-positive hemophiliacs; 11 of the women were not HIV seropositive and 4 were. None of the couples was abstaining from sexual intercourse, and during the 4 weeks prior to responding, the couples had intercourse a mean of 6.2 times. Sixty percent always used condoms, 13 percent did so most of the time, and the remaining 27 percent did sometimes. Condom use was not significantly related to either frequency of intercourse, the women's knowledge of acquired immunodeficiency syndrome (AIDS) and AIDS-risk reduction, the actual HIV status of both partners and the women's perceived status of both, the extent of the women's worry about contracting AIDS, their reported degree of negative impact from AIDS, or to their mood, age, or education. All women who reported not always using condoms had been informed of their own and their partner's HIV status; were counseled repeatedly regarding risk reduction; acknowledged the possibility of heterosexual HIV transmission; said they knew of recommendations for the use of condoms; recognized their risk of HIV infection; claimed some degree of worry about acquiring HIV through sexual activity; had children at home; and were not, with one exception, trying to become pregnant. There were several possible factors influencing the decision by women at high risk for acquiring HIV not to use condoms. Among them were complaints that the women found condoms unpleasant or an unwanted reminder of AIDS, a sense of obligation or a drive to continue unaltered sexual relations, the false reassurance of HIV-negative test results for some of the women who did not always use condoms, a willingness to sacrifice and to share their partner's fate, a desire to avoid communicating rejection and adding to their partner's burdens, and difficulty changing long-standing behavior patterns despite logical understanding of the risks involved. PMID- 1410232 TI - One state's response to the malpractice insurance crisis: North Carolina's Rural Obstetrical Care Incentive Program. AB - In the period 1985-89, there was a severe drop in obstetrical services in rural areas of North Carolina, partly because of rising malpractice insurance rates. The State government responded with the Rural Obstetrical Care Incentive (ROCI) Program that provides a malpractice insurance subsidy of up to $6,500 per participating physician per year. Enacted into law in 1988, the ROCI Program was expanded in 1991, making certified nurse midwives eligible to receive subsidies of up to $3,000 per year. To participate, practitioners must provide obstetrical care to all women, regardless of their ability to pay for services. Total funding for the program has increased from $240,000 to $840,000, in spite of extreme budgetary constraints faced by the State. The program and how its implementation has maintained or increased access to obstetrical care in participating counties are described on the basis of site visits to local health departments in participating counties and data from the North Carolina Division of Maternal and Child Health. The program is of significance to policy makers nationwide as both a response to rising malpractice insurance rates and reduced access to obstetrical care in rural areas, and as an innovative, nontraditional State program in which the locus of decision making is at the county level. PMID- 1410233 TI - Measuring the quality of life of the elderly in health promotion intervention clinical trials. AB - The Multicenter Trials of Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) is a series of clinical trials of biomedical, behavioral, and environmental interventions to reduce the risks of frailty and injury among the elderly. Reliable assessment of the quality of life reported by the subjects is a central issue in evaluating the interventions. An intervention may have a significant impact on an elderly person's sense of well-being, even though significant improvement is not observed in selected physical outcome measures. Elderly persons' compliance with particular intervention regimens may be influenced by the quality of life effects that they perceive in relation to the intervention. The researchers review the definition and measurement of quality of life in the trials, with particular attention to issues in determining common measures used at all study locations. Practical considerations in the selection and use of quality of life measures in both community and institutional populations are addressed. Topics discussed include the interrelation of aging, functional capacities, and quality of life; the multi-dimensionality of quality of life in relation to differential intervention effects; and age-related issues in the collection of quality of life data. Preliminary observations are reviewed, and potential contributions of FICSIT to intervention-sensitive quality of life assessments among the elderly are noted. PMID- 1410234 TI - North Florida is part of the stroke belt. AB - Florida is the only State in the southeastern United States that is not part of the "stroke belt." The National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, defines the stroke belt as those States with an age-adjusted stroke mortality rate for the years 1979 to 1981 that is more than 10 percent above the national annual rate of 40.3 per 100,000 population. By reproducing at the county level the methods that were used at the State level to describe the stroke belt, the authors identified a group of 34 contiguous northern Florida counties (population exceeds 2 million) with an age-adjusted stroke mortality rate of 47.2 per 100,000--higher than 3 of the 11 stroke belt States. They concluded that north Florida is part of the stroke belt and should be included as a priority region for stroke prevention programs. County-level analyses that are methodologically comparable with those used by NHLBI to describe the stroke belt may be a useful technique for identifying high stroke rate regions within States which might be missed when needs assessment is based only on State-level data. PMID- 1410235 TI - Cultural barriers to health care for southeast Asian refugees. AB - Many Southeast Asians now living in the United States experience severe health problems, attributable to physical trauma and inadequate health care in Asia, and low socioeconomic status in this country. Evidence indicates that despite their health problems, Southeast Asian refugees underuse the American health care system. Cultural reasons for this underuse are examined. Southeast Asian cultural attitudes toward suffering, such as beliefs that suffering is inevitable or that one's life span is predetermined, can cause Southeast Asians not to seek health care. Cultural beliefs about the sources of illness and correspondingly appropriate forms of treatment can be a barrier to Western health care. Many lack familiarity with Western diagnostic techniques and treatments and thus are apprehensive. Health care providers' ignorance of Southeast Asian cultures can interfere with communication with patients, resulting in culturally irrelevant services or misinterpretation of side effects of Southeast Asian folk medicines. Southeast Asians' lack of familiarity with American culture can make health care services geographically and economically inaccessible and can cause Southeast Asians to be ignorant of available services or how to access them. An understanding of Southeast Asian cultures and additional outreach efforts by Western medical practitioners and health care providers are needed to improve the use of health care services by Southeast Asian refugees in this country. PMID- 1410237 TI - The hepatitis B immunization campaign for children in the Federated States of Micronesia. AB - Hepatitis B has long been recognized as hyperendemic among persons residing in the western Pacific. Effective control strategies have not been described. From December 1988 through October 1989, the Federated States of Micronesia (FSM) conducted a campaign to immunize children through age 6 years with three doses of hepatitis B (HB) vaccine. In addition, HB vaccination was incorporated into the routine immunization schedule for all children born in FSM, with the first dose given to newborns. Between December 1988 and October 1989, a total of 64,085 doses of HB vaccine were administered to the children. After the start of the campaign, the subject group was enlarged to include children through 15 years of age in the States of Yap and Kosrae. Fifty-nine percent of the enlarged group in all States received a complete series of HB vaccinations. During each client encounter, individual immunization records were examined and diphtheria-pertussis tetanus, oral polio vaccine, and measles-mumps-rubella antigens were administered to children who were not adequately immunized. The annual immunization assessment for 1990 showed coverage improved significantly from previous years in every FSM State. PMID- 1410236 TI - Family versus individually oriented intervention for weight loss in Mexican American women. AB - Mexican Americans are more likely to be obese than non-Hispanic whites, yet little research has been conducted on the treatment of obesity in Mexican Americans. The purpose of this study was to compare a family-based intervention with a traditional program oriented to the individual for achieving weight loss by obese Mexican American women. A total of 168 obese women were randomly assigned to one of three groups. Group 1 served as a comparison group and received only printed materials on nutrition, exercise, and behavioral principles for weight loss. Subjects in the individual group (group 2) received the same printed information, but they also attended classes led by bilingual registered dietitians. Subjects in the family group (group 3) received materials and attended classes that emphasized a family-oriented approach to making changes in eating habits and exercise behavior. Spouses and children attended classes with subjects in this group. Results revealed a significant linear trend in both body mass index and weight reduction across the groups, with losses greatest in the family group, followed by the individual group, and least in the comparison group. Both the individual and the family groups lost significantly more weight than the comparison group, although the difference between these two groups was not statistically significant. The results suggest that a culturally and linguistically appropriate program can achieve significant weight reduction among Mexican Americans. More research should be conducted on the effects of family and other types of social support on weight loss by Mexican Americans. PMID- 1410238 TI - Increasing participation by private physicians in the EPSDT Program in rural North Carolina. AB - This study evaluated a method to increase physicians' participation in Early and Periodic Screening, Diagnosis and Treatment (EPSDT), a preventive health care program for Medicaid eligible children. Use of EPSDT can improve children's health status and reduce health care costs. Although the potential benefits of EPSDT are clear, the program is underused; low rates of participation by private physicians contribute to underuse. This study targeted a population of 73 primary care physicians in six rural counties in North Carolina where the physician supply, their participation in EPSDT, and use of EPSDT were low. A mailed intervention packet attempted to address barriers to participation perceived by private providers. The packet consisted of a carefully constructed letter, an informative journal article, and an educational pamphlet. Participation in EPSDT screening increased from 15 to 25 private physicians (67 percent), at a cost, on average, of less than $30 per recruited provider. Suggestions are presented for adapting the intervention packet to other settings. PMID- 1410239 TI - Comparison of Native American births in upstate New York with other race births, 1980-86. AB - The purpose of this study was to describe the neonatal characteristics of Native American (Indian) infants and the antenatal characteristics of their mothers as compared with white, black, and other race infants. The study population comprised 979,444 live births to upstate New York (exclusive of New York City) resident mothers between 1980 and 1986. Data were abstracted from vital records (birth certificates) and analyzed using a variety of descriptive statistics. Mothers of Native American and black infants had similar antenatal profiles (that is, younger, higher parity, lower educational attainment, and delayed initiation of prenatal care), which differed from mothers of white or other race infants. Despite having at-risk mothers, Native American infants were similar to white and other race infants with respect to the percentage of births that were considered low birth weight or premature. Black infants were twice as likely as the other three groups of infants to be low birth weight or premature. These findings suggest that other factors appear to be important in determining neonatal outcome and that typical at-risk antenatal profile of mothers may not be consistent across all racial groups. PMID- 1410240 TI - Factors influencing the effectiveness of mailed health surveys. AB - The authors investigated sources of bias in health surveys by examining responses to their 1989 questionnaire mailed to 1,255 Massachusetts men who were eligible for dental care provided by the Department of Veterans Affairs. After a maximum of three mailings and one telephone call to nonrespondents, a total of 1,049 veterans had responded out of 1,228 finally determined to be eligible, a response rate of 85 percent. The investigators found that small differences in univariate estimates would have occurred had the field phase been terminated after the first mailing, which had a response rate of 61 percent. To evaluate multivariate distributions, they duplicated their previously published logistic regression model for sources of dental care, using only those who responded to the first and second mailings. Although model fits would have been substantively the same had the field phase been terminated after the first or the second mailings, analysis of parameter estimates and their statistical significances suggested bias that would have led to different substantive conclusions, in some instances. Another potential source of bias in surveys was found to be item omission. Fifty-eight percent of respondents answered all 46 survey questions, and 90 percent answered at least 91 percent of the questions. Fewer questions were answered by those whose responses were received last, but trends regarding missing data by age or education were not statistically significant. Although the survey using this methodology met all objectives, subject nonresponses, the ineligibility of potential respondents, item nonresponses, and skewed distributions of outcome variables combined to reduce the statistical power to detect differences among groups or to alter the analysis of the differences. These factors need to be planned for by investigators undertaking similar surveys. PMID- 1410241 TI - Using after-shelter case management to improve outcomes for families with children. AB - Homelessness and living in shelters have complex and multiple adverse effects on children that lend urgency to assisting families with children to leave shelters and to achieve independent and stable living arrangements. Some shelters offer only short-term housing with no additional support services. Others offer long stays with a comprehensive range of social and economic support services. While living in a shelter, families are faced with such major challenges as finding employment that is adequate to meeting the family's financial needs and locating permanent housing. Because shelter or street living may exacerbate children's health and developmental problems, families with children should move from them into a stable home situation as quickly as possible. The researchers examined some of the specific effects of living in a shelter for homeless families with children in Virginia Beach, VA. They focused on whether the policy of offering families after-shelter case management services for 1 year decreased their average length of the time in the shelter, and whether case management of families with children for 1 year after leaving a shelter increased the proportion of families who obtained permanent housing. A non experimental descriptive design was used. In case management after the shelter stay, an advisor worked intensively with families, helping to locate resources and serving as a resource link, assisting with application processes, providing transportation when necessary, and acting as advocate and support person. Some families needed minimal assistance, while others needed more intensive assistance. The findings suggest that case management services for families following discharge from a homeless shelter effectively reduces the length of stay ina shelter and increases housing stability after discharge from the shelter. For this sample, the average shelter stay was reduced from 31.1 to 22.8 days. PMID- 1410242 TI - Cigarette use among Arab Americans in the Detroit metropolitan area. AB - Use of cigarette tobacco by large proportions of the population of Middle Eastern countries has been reported; however, little is known about smoking behavior in one of America's fastest growing minorities, the Arab Americans. The purpose of this study was to examine cigarette smoking behavior of 237 randomly selected Arab American adults from a telephone listing in the Detroit area. Participants lived in the geographic Arab American community and identified with a Middle Eastern cultural heritage. Nurses, who spoke both English and Arabic, interviewed one adult family member using the 59-item self-report from the Cardiovascular Risk Factor Survey developed by Rice. Mean age of respondents was 40.4 years, 97 percent had been born in the Middle East, and 67 percent had been living in the United States 15 years or less. Current smokers rate was 38.9 percent, former smokers rate was 11.1 percent, never smokers rate was 50 percent, and the quit ratio (proportion of ever smokers who are former smokers) was 22.2 percent. Fifty four percent of the current smokers were between 25 and 34 years of age; fewer women than men were former smokers, and the highest proportion of current smokers were Lebanese. Subjects who had smoked for the longest time were the least well educated. Arab Americans in this sample had a higher smoking rate, a lower quitting rate, and a much lower quit ratio when compared with national and State of Michigan data. With the growing numbers of Middle Eastern immigrants, there is potential for a dramatic increase in smoking-related health problems. PMID- 1410244 TI - Prevention efforts slow worldwide spread of HIV, WHO report says. PMID- 1410243 TI - Bacterial infections and skin cleaning prior to injection among intravenous drug users. AB - In a survey of 1,057 active intravenous drug users in Baltimore, MD, who were recruited through extensive community outreach, 12 reported endocarditis and 113 reported subcutaneous abscesses in the 6 months before being interviewed. Of all the persons surveyed, 556 reported cleaning their skin prior to injection at any time and 173 reported cleaning their skin all the time in the 6 months before the interview. The frequency of subcutaneous abscesses was lower among those who reported skin cleaning all the time; a similar trend was noted for frequency of endocarditis. The relatively simple procedure of encouraging intravenous drug users to clean their skin prior to injection will not eliminate but might reduce the frequency of these serious and expensive infectious complications of intravenous drug use. PMID- 1410245 TI - Bursting the chewing gum bubble. PMID- 1410247 TI - Restoration of endodontically treated teeth using a combined amalgam-composite resin technique. AB - This article describes a combined amalgam-composite resin technique for the restoration of endodontically treated molars suffering from severe, subgingival coronal damage. The use of silver amalgam in the subgingival areas provides an effective interface and a proper barrier for restoring and reinforcing the rest of the crown with a composite resin material. PMID- 1410246 TI - Effect of gum chewing following food ingestion on the pH of interproximal dental plaque. AB - Recent publications have suggested that chewing sorbitol- or sucrose-containing gum after a snack or meal can reduce development of caries by neutralizing dental plaque acids at interproximal sites in the dentition. To confirm these findings four volunteers wore appliances containing a miniature pH electrode. After plaque accumulation, subjects ingested a bowl of sugar-coated cereal with milk and 20 minutes later chewed a sorbitol-containing gum, a sucrose-containing gum, or did not chew anything for 20 minutes. After exposure to the cereal, the plaque pH fell within 20 minutes from approximately 6.4 to 4.8. Sorbitol gum caused the pH to rise to 5.5, while the sucrose gum caused the pH to rise to only 5.1. After cessation of chewing, the pH in all cases dropped to 4.5 or lower. No statistically significant difference could be shown between plaque pH changes with the various protocols. Gum chewing after eating caused only a transient elevation in plaque pH. PMID- 1410248 TI - Dentin- and enamel-bonded Class V composite resin restoration. AB - Improvements in dental materials and methods of their use necessitate continuing modifications of clinical techniques. This paper details a step-by-step procedure for restoring a Class V carious lesion with polishable, visible light polymerizing composite resin combined with one of the new-generation dentin enamel bonding systems. PMID- 1410249 TI - History, safety, and effectiveness of current bleaching techniques and applications of the nightguard vital bleaching technique. AB - This article reviews the literature on the use of hydrogen peroxide in three professionally administered bleaching techniques from historical, technique, and safety viewpoints. Safety over time, absolute safety, and relative safety of nonvital bleaching, in-office vital bleaching, nightguard vital bleaching, and over-the-counter bleaching kits are compared. The advantages and disadvantages of different bleaching options, as well as indications for individual or combined use of the techniques, are discussed. In addition, specific indications for the use of the nightguard vital bleaching technique are presented. PMID- 1410250 TI - Effects of home bleaching products on composite resins. AB - A number of home bleaching products have recently been introduced. This in vitro study evaluated the effect of three representative bleaching products on the microhardness and surface texture of hybrid and microfilled composite resins. Scanning electron microscopic examination revealed cracking of the microfilled specimens treated with carbamide peroxide gels (Proxigel and White & Brite). White & Brite also caused slight roughening of the hybrid composite resin. Microhardness tests indicated that the treated composite resins became somewhat softer. However, the only statistically significant softening was associated with White & Brite. PMID- 1410251 TI - Pneumatic versus hand condensation of amalgam: effect on microleakage. AB - This study compared two techniques of amalgam condensation for effect on early microleakage. Class V preparations were restored with a high-copper amalgam using pneumatic condensation or conventional hand condensation. Significantly less microleakage was observed when pneumatic condensation was used. Further, pneumatic condensation proved equally effective in reducing early microleakage whether or not a dentinal sealant was used as an intermediary. PMID- 1410252 TI - Adaptation and condensation of amalgam restorations in Class II preparations of conventional and conservative design. AB - The purpose of this study was to investigate in vitro the adaptation and condensation of the proximal section of amalgam restorations placed in Class II preparations of conventional and conservative designs. The amalgam restorations were placed with traditional hand instruments with and without the aid of an automatic amalgam condenser. The restorations and sections of the restored teeth were examined and scored for adaptation and porosity. The restorations in the preparations of conservative design, especially those placed without the aid of the automatic condenser, exhibited more adaptation defects, porosity, and voids than did the restorations in the preparations of conventional design. It is necessary to identify and describe instruments and techniques that will facilitate the placement of amalgam restorations in preparations with limited access. PMID- 1410253 TI - Microleakage of etched-dentin composite resin restorations. AB - Some clinicians now advocate dentinal etching to eliminate microleakage around composite resin margins. This study evaluated the "Kanca technique" and three commercial dentinal adhesives, including Clearfil Photo Bond, which uses phosphoric acid to etch dentin. The Kanca technique and Tenure were the most effective systems tested. However, none of the bonding systems completely eliminated microleakage. Total sealing of dentinal margins is not predictable with current adhesives and composite resins. PMID- 1410254 TI - Periodontal changes in furcations resulting from orthodontic uprighting of mandibular molars. AB - Periodontal examinations were carried out preorthodontically and again 2 to 28 months after orthodontic uprighting of 20 molars (40 furcation areas) in 16 patients. Preorthodontically, patients presented with generalized periodontitis. Postorthodontically, nine of 20 buccal furcations had become more severe, one had improved, and ten remained unchanged. Lingually, nine worsened, and 11 had no change. Furcation area pocket depths increased in 35.0% of furcations, but did not change in 57.5%. Furcation root form was not associated with the degree of change. Possible mesial root extrusion was found in 60.0% of the uprighted molars. The molars showing root extrusion had furcations that increased in severity. Heavy uprighting forces contributed to extrusion, and some effect may have been due to periodontal inflammation and bone loss. Mandibular molars can be uprighted in patients with moderate periodontitis, but light intrusive forces in an inflammation-free environment are recommended. PMID- 1410255 TI - Amalgam repair: a case report. AB - Through the report of a clinical case, the feasibility and advantages of repair and recontouring of complex amalgam restorations are discussed. In this patient, the kind of alloy used for the fractured restoration and the age of the restoration were known factors. Additional mechanical retention was prepared in both the "old" amalgam and the dentin, and the repair was made with a high-copper alloy. The bond at the repair site was stable at the 2.5-year recall examination. PMID- 1410256 TI - Cermet reinforcement of a weakened endodontically treated root: a case report. AB - Many clinical applications have been recommended for glass-cermet cement because of its improved properties compared to the original glass-ionomer cements. It has also been accepted as a dentinal substitute that can strengthen teeth. In this paper, an additional clinical application for glass-cermet cement, the reinforcement of weakened endodontically treated roots, is suggested. This technique is in keeping with the trends of tooth conservation and the use of an adhesive restorative material in the restoration of severely damaged teeth by a conservative approach. PMID- 1410258 TI - Pontic repair of a porcelain-fused-to-metal fixed partial denture with a castable ceramic material. PMID- 1410257 TI - Tooth discoloration resulting from long-term tetracycline therapy: a case report. AB - Administration of tetracycline to children or pregnant women is known to adversely affect the color of developing teeth. This case report suggests the possibility that discoloration from tetracycline may not be limited to tooth development in the child, but may also affect the adult dentition. When given over long periods of time in adults, the tetracycline molecule is incorporated into the continuously forming secondary dentin. It is possible that chronic sun exposure of the incorporated tetracycline may cause the formation of a reddish purple oxidation product, resulting in discoloration of the permanent teeth. PMID- 1410259 TI - An update of a one-appointment master impression and jaw relation record technique. AB - Dentists may want to consider using an update of a unique complete denture technique that saves total chair time and, therefore, decreases cost. The technique combines appointments two and three, during which time the dentist both makes the master impressions and records the maxillomandibular relationships. In the past, protection of the maxillomandibular relationship records during the subsequent laboratory work was a problem. By applying new, tough, and thin denture base materials to the technique, the dentist will be less likely to distort the maxillomandibular records while boxing and pouring the impressions. PMID- 1410260 TI - Origination and progression of microleakage in a restoration with a smear layer mediated dentinal bonding agent. AB - Several recently marketed dentinal bonding agents modify, but do not remove, the smear layer. Some controversy exists as to whether the smear layer should be left in place or completely removed from preparations to be restored with composite resin systems. This study utilized scanning electron microscopy with energy dispersive x-ray analysis to evaluate the pathway of microleakage in a composite resin restorative material that utilizes a smear layer-mediated dentinal bonding agent. Microleakage occurred at the smear layer-dentin interface and progressed into both the smear layer and dentinal tubules, suggesting that the smear layer acts as a pathway for microleakage. PMID- 1410261 TI - One-year clinical evaluation of an anterior composite resin. AB - An anterior composite resin was evaluated in a clinical study of 93 Class III and Class IV restorations placed in patients aged 12 to 50 years. The restorations were evaluated at baseline, 6 months, and 1 year. Sixty-four (79%) of the 81 restorations examined at the 1-year recall were unchanged. Marginal discoloration and changes in surface appearance and marginal adaptation accounted for most of the changes. All changes appeared in patients younger than 14 years, which may indicate that the patients had problems in oral hygiene. Replicas of randomly selected restorations showed smooth surfaces and well-sealed margins with a smooth transition from restoration to enamel. Some restorations showed marginal breakdown and a pitted irregular surface. PMID- 1410262 TI - The shear bond strength between human enamel and composite resin placed with cured or uncured unfilled resin. AB - The shear bond strength between enamel and composite resin placed with an unfilled resin layer was tested under several conditions: The unfilled resin layer was either blown thin or left unthinned, and pre-cured alone or cured with the composite resin. Shear testing showed that the bond to enamel was slightly enhanced for Pekalux and was significantly enhanced for Durafill VS when the unfilled resin was not pre-cured. Thinning of unfilled resin slightly increased the bond strength of Pekalux and decreased the bond strength of Durafill VS. A majority of the specimens fractured at the composite resin-unfilled resin interface, and more than half of all interface failures occurred in specimens in which the unfilled resin had been pre-cured. The results indicated that the link between composite resin and the unfilled resin layer was enhanced by simultaneous curing. PMID- 1410263 TI - Dry socket: frequency of occurrence after intraligamentary anesthesia. AB - To determine whether the use of intraligamentary anesthesia increases the incidence of dry socket, results of 305 extractions of mandibular molars in two groups of patients were studied. In the first group, inferior alveolar nerve block was applied, and, in the second, intraligamentary anesthesia was applied. A solution of 2% lidocaine with 1:80,000 epinephrine was used. Statistical analysis of the postoperative occurrence of dry socket indicated that the use of intraligamentary anesthesia did not result in a higher frequency of dry socket than did conventional anesthesia. PMID- 1410264 TI - Dental caries and stress among South African political refugees. AB - The aim of this study, which was conducted in a refugee camp of the African National Congress in Tanzania, was to analyze the caries experience in relation to perceived stress and sleeping problems and stressful experiences among South African political refugees. A sample of 194 persons, aged 11 to 39 years, was examined clinically and interviewed. There was a consistent association between caries experience and the different parameters for estimating perceived and experienced stress. In particular, the aggregation of different stress indicators seemed be strongly related to higher caries experience. PMID- 1410265 TI - Interaction between radiation and drug damage in mammalian cells. VI. Radiation and doxorubicin age-response function of doxorubicin-sensitive and -resistant Chinese hamster cells. AB - A comparative study of the radiation and/or doxorubicin (DOX) survival response for synchronous populations of Chinese hamster V79 cells and two DOX-resistant variants (77A and LZ-8) was performed. The greatest cellular radiation sensitivity was observed in mitosis, while the greatest resistance was observed during late S phase for the three cell lines. The variation in radiation response throughout the cell cycle was expressed as a change in the width of the shoulder of the survival curves (Dq) with little change in D0. This suggests that each phase of the cell cycle has a different capacity for accumulation of radiation injury. The radiation age-response function for the three cell lines revealed that 77A and LZ-8 cells were more radiosensitive than V79 cells throughout the cell cycle. Exposure of synchronous populations to DOX (1.84 microM for V79, 9.21 microM for 77A, and 921 microM for LZ-8) for 1 h as a function of cell cycle phase revealed that V79, 77A, and LZ-8 cells exhibited the greatest sensitivity to DOX in mitosis and the most resistance to DOX during S phase, as indicated by the differences in the slope of the initial component of the survival curve. Levels of P-glyco-protein (P-gp) are probably not a factor contributing to DOX age-response function since P-gp levels remain constant throughout the cell cycle in all three cell lines. Synchronous populations of V79, 77A, and LZ-8 cells sequentially treated with DOX and radiation at various cell cycle phases were also analyzed. The results showed that the interaction between radiation and DOX damage resulted in a reduced cellular capacity for the accumulation of radiation damage throughout the cell cycle, as indicated by a decrease in the width of the shoulder of the survival curve. Overall, both DOX-sensitive V79 cells and DOX resistant 77A and LZ-8 cells exhibited (1) a similar age-response function for radiation or DOX, and (2) no differences in the effects of DOX on radiation induced damage throughout the cell cycle. These results indicate that acquired resistance to DOX associated with increased levels of P-gp in the cell membrane did not appear to affect the age-response function for radiation or DOX, and the nature of the interaction between damage caused by radiation and DOX was also not affected. PMID- 1410266 TI - Relative biological effectiveness of 50-MV X rays on jejunal crypt survival in vivo. AB - Earlier in vitro studies of relative biological effectiveness (RBE) of 50-MV X rays show an RBE of approximately 1.1 compared to 4 MV. No difference in RBE has been found for 20-MV X rays or 50-MeV electrons. The higher RBE for 50 MV can be explained to some extent by the small high linear energy transfer contribution from photonuclear reactions at high X-ray energies. To investigate the validity of the results in vitro, a study of the RBE of 50-MV X rays has been performed in vivo using the jejunal crypt microcolony assay in mice. The reference radiation used in this case was 20-MV X rays. The results confirm the earlier in vitro studies. The RBE for 50-MV X rays was estimated to be 1.06, calculated as the ratio between the slopes of the response curves. PMID- 1410267 TI - The clonogen content of murine intestinal crypts: dependence on radiation dose used in its determination. AB - The number of colony-forming (clonogenic) cells in each of the crypts in mouse small intestine was deduced using a two-dose irradiation technique. The number was 7.5 +/- 0.8 cells using two equal doses each less than 9 Gy and 38 +/- 7 cells using 9 Gy or more per dose. The significant dose dependence could not be accounted for by considerations of intra- or intercrypt variability, or by the factor introduced to correct the sampling frequency for the influence of crypt size. The results suggest that more colony-forming cells may be recruited when the injury is more severe. PMID- 1410268 TI - The effect of light fluence rate in photodynamic therapy of normal rat brain. AB - This paper reports the effect of incident light fluence rate on the depth to which necrotic lesions are produced by photodynamic therapy (PDT) in the brains of normal Fisher rats. The rats were injected intraperitoneally with Photofrin (12.5 mg kg-1) 48 h prior to PDT with a fixed incident fluence of 35 J cm-2. The treatment was performed at 10, 50, 100, and 200 mW cm-2 and also in a periodic manner (30 s "on" at 100 mW cm-2, 30 s "off"). The depth to which necrosis occurred was determined 24 h after treatment by microscopic examination of tissue sections. No differences were found in the depth to which necrosis was produced by any of the five irradiation schedules. This finding is discussed in the context of other published dose-rate experiments. PMID- 1410269 TI - Comments on "Radiation-induced DNA unwinding is influenced by cell shape and trypsin". PMID- 1410270 TI - A comparison of the predicted risks of developing osteosarcoma for dogs exposed to 238PuO2 based on average bone dose or endosteal cell dose. AB - Dose-response relationships observed in laboratory animals can be used to identify possible human risk factors and may also be used in a quantitative manner when human data are not available. This paper presents an analysis of the dose dependency of osteosarcoma incidence in beagle dogs given a single inhalation exposure to a monodisperse aerosol of 238PuO2. We were particularly interested in comparing the predicted risks that were based on average bone dose with those based on endosteal cell dose and in evaluating the advantages of using a more biologically relevant cell-specific dose in risk estimation. The endosteal cell dose was calculated using the method of Marshall et al. (Health Phys. 35, 91 101, 1978), as extended to account for exposure by inhalation. The relationship between dose and time to tumor was analyzed by the proportional hazards regression model. The probability of developing osteosarcoma was strongly dependent on dose for dogs receiving low doses, but this was not true for dogs receiving high doses. The predicted risk based on endosteal cell dose was not consistently higher or lower than the risk based on average bone dose at various times after exposure, because the relationship between these two doses was not linear with respect to time. Also, as a result of the nonlinear relationship between these two doses, the risk estimated based on endosteal cell dose would not be a fixed factor of that based on the average dose. Random errors in the measured initial lung burden had a relatively large impact on the predicted risk based on endosteal cell dose, and the difference between the estimated risk of developing osteosarcoma based on endosteal cell dose and that based on average bone dose is likely to be within the error margins of the estimated risks. PMID- 1410271 TI - Essential metalloelement metabolism and radiation protection and recovery. AB - Understanding the metabolism of essential metalloelements and their role in tissue maintenance and function as well as the roles of essential metalloelement dependent enzymes in responding to injury offers a new approach to preventing and/or treating radiation injury. This review presents the roles of some essential metalloelement-dependent enzymes in the maintenance and function of tissues and their responses to radiation injury and gives an account of the observed effects of nontoxic doses of essential metalloelement compounds on protection against radiation damage and its recovery. The radiolysis of chemical bonds and free radicals derived from oxygen accounts for the acute and chronic aspects of radiation injury. The recognized biochemical roles of essential metalloelements and their observed pharmacological effects predict the therapeutic usefulness of essential metalloelement complexes in the prevention and/or treatment of radiation injury. Copper complexes have radiation protection and radiation recovery activities and cause rapid recovery of immunocompetence and radiation-induced damage to cells and tissues. Recently, iron, manganese, and zinc complexes have also been found to prevent death in lethally irradiated mice. These pharmacological effects of essential metalloelement complexes can be understood to be due to facilitation of de novo synthesis of essential metalloelement-dependent enzymes which have roles in preventing the accumulation of pathological concentrations of oxygen radicals or repairing damage caused by radiation-induced bond homolysis. Essential metalloelement complexes offer a physiological approach to prevention and/or treatment of radiation injury. PMID- 1410272 TI - Comparisons of cellular radiation response using absolute rather than relative parameters. AB - One important goal of radiobiology is to describe the response to radiation damage in quantitative terms. Because the dose response is nonlinear, this typically involves the comparison of several dose-dependent parameters. Past attempts at simplifying this process have often involved manipulations of these dose-dependent parameters to derive a single comparative number. Unfortunately, the advantages of a single comparative number, often a ratio or even a ratio of ratios, can be outweighed by the loss of significant biological information. Examples are given in four areas of research: (1) definition of radiation response at clinically relevant radiation doses, (2) modification of radiation sensitivity by oxygen, (3) effects of combined radiation modifiers (e.g., sensitizers and protectors), and (4) comparisons of radiation modifiers in different dose/response regions. In each area, to define and compare dose response, we propose the use of consistent, simple, and absolute radiation response parameters: the inverse dose (or dose) required to produce a given effect. The use of absolute sensitivity (or resistance) avoids the use of many other parameters, ratios, and definitions and permits a uniform and unambiguous description of "radiation response." PMID- 1410273 TI - Lymph flow from murine footpad tumors before and after sublethal hyperthermia. AB - The effect of local hyperthermia (43.5 degrees C for 1 h) on lymph flow from B16 F10 tumor-bearing foot pads of C57BL/6 mice was measured by monitoring the clearance of 99mTc-labeled human serum albumin. The foot was represented by a single-compartment model enabling a quantitative computation of lymphatic flow from the tumor to regional lymph nodes. Lymphatic flow from untreated tumors was 0.0059 +/- 0.0011 ml/min cm3 compared to 0.0118 +/- 0.0027 ml/min cm3 lymphatic flow from tumors immediately following heating. Morphological alterations in tumor blood vessels result in their high vascular permeability. The increase in lymphatic clearance from tumors after sublethal hyperthermia is compatible with the increase in interstitial fluid formation in tumors based on Starling's Law. PMID- 1410274 TI - Radiation-induced micrencephaly in guinea pigs. AB - The effect of X rays on brain weight of guinea pig pups at birth was studied in 21-day-old embryos exposed in utero to doses of 75 and 100 mGy. When compared to controls and when corrected for body weight, gestation time, litter size, sex, and examiner differences, the brains of irradiated pups weighed approximately 46 mg less than those of controls (P < 0.001) for the 75-mGy group and about 55 mg less for the 100-mGy group. Brains of females weighed 51 mg less than those of males of the same body weight. Dam weight and caging conditions had no observed effect on brain weight. PMID- 1410276 TI - The effect of superhelical density on the yield of single-strand breaks in gamma irradiated plasmid DNA. AB - Using agarose gel electrophoresis, the formation of DNA single-strand breaks (SSBs) by 137Cs gamma irradiation was quantified in negatively supercoiled topological isomers of plasmid pUC18. The G value for SSB formation falls slightly from 1 x 10(8) to 8 x 10(-9) SSB Gy-1 Da-1 as the superhelical density varies from 0.00 to -0.08. This result is not in agreement with recent observations by others which suggest that increasing the negative superhelical density of plasmid DNA increases its sensitivity to X irradiation. PMID- 1410275 TI - Effects of the calcium channel blocker flunarizine on the hemodynamics and oxygenation of tumor microvasculature. AB - Flunarizine is a diphenylpiperazine calcium entry blocker that has been shown previously to increase tumor blood flow and sensitivity to radiotherapy via reduction in the radiobiologically significant hypoxic fraction. Two mechanisms of action have been proposed previously (vasodilation, altered blood viscosity), but no studies have been performed to examine its mechanisms of action in vivo. Such information would be invaluable in determining the role of flunarizine in multimodality approaches to reduce tumor hypoxia. Fisher-344 rats bearing R3230Ac tumors transplanted into dorsal flap window chambers were used to examine microcirculatory changes after administration of flunarizine (1.0 mg/kg, iv). The drug increased the diameters of the microvasculature and red cell velocities specifically in central tumor regions (producing an average increase in vessel flow by a factor of 1.96), which was accompanied by an increase in perivascular pO2 of 12 mm Hg, on the average. The drug did not change the diameters of tumor "feeding" vessels, nor did it change vascular length densities. Thus the improvement in central tumor blood flow and oxygenation could not be attributed to dilation of feeding vessels. The oxygen-carrying capacity of the blood was not altered either since hemoglobin saturation (measured in vitro) and the hematocrits of the microvasculature were unchanged after drug administration. Therefore, by a process of elimination, the most likely explanation for the effect of the drug is modification of blood viscosity. Additional studies are under way in this laboratory to examine whether changes in viscosity occur after flunarizine administration. PMID- 1410277 TI - Radiation-induced inactivation of dihydroorotate dehydrogenase in dilute aqueous solution. AB - The inactivation of dihydroorotate dehydrogenase by gamma irradiation in dilute aqueous solution has been investigated. The activity of the enzyme decreased exponentially as a function of the absorbed dose under aerated and nitrous oxide saturated conditions. The contributions of the individual radical species derived from water radiolysis were estimated from the inactivation results observed under aerated, argon-saturated, and nitrous oxide-saturated conditions. The hydrogen atom and hydroxyl radical were found to be important in enzyme inactivation. The effect of selected inorganic radical anions such as Br.2-, I.2-, and (SCN).2- on the enzyme activity was also studied, and the results implicate the possible involvement of cysteine and tyrosine residues in the catalytic activity of dihydroorotate dehydrogenase. Changes in the kinetic parameters (Michaelis-Menten constant, Km, and maximal velocity, Vmax) due to irradiation under the conditions investigated suggest that radiation-induced inactivation is due to modification of the substrate binding sites and that of the active site residues in the enzyme. Evidence for the reduction of iron-sulfur centers in the enzyme during the inactivation process has been put forward from the difference spectrum of the irradiated dihydroorotate dehydrogenase. It has also been shown by electrophoretic studies that radiation-induced inactivation was not due to any fragmentation of the protein structure or the formation of any intermolecular crosslinking. PMID- 1410278 TI - Thrombopoietin from human embryonic kidney cells causes increased thrombocytopoiesis in sublethally irradiated mice. AB - Previous work showed that mice treated with platelet-specific antiserum prior to whole-body irradiation did not suffer the degree or duration of thrombocytopenia as did irradiated control mice. We now report that a partially purified preparation of a thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) mimics the biological effects of platelet-specific antiserum treatment in hematopoietically suppressed mice. Male C3H mice were exposed to 3.0 or 4.5 Gy of 137Cs gamma radiation and injected with a total dose of 4 units (U) of TSF. Human serum albumin (HSA) and rabbit anti-mouse platelet serum-injected mice, along with unirradiated mice, served as controls. Packed cell volumes (PCV), RBC counts, WBC counts, platelet counts, and percentage 35S incorporation into platelets were measured in mice at various days (7-14) following treatment. The results showed that irradiated mice treated with TSF had increased 35S uptake into platelets and higher platelet counts than HSA-treated controls. Also, PCV, RBC counts, and WBC counts of irradiated mice treated with TSF were significantly higher than values for HSA-treated mice. Additional experiments using 40,000 U/mouse of Interleukin-6 (IL-6), 227 U/mouse of granulocyte macrophage-colony stimulating factor (GM-CSF), or a combination of GM-CSF and IL-6 did not show increased platelet counts or 35S incorporation into platelets on Days 10 and 14 when compared to other mice treated with control substances. These results suggest that the radioprotective effects of platelet antibodies reported previously may be due to the release and action of thrombopoietin. These studies also demonstrate that thrombopoietin therapy will modulate the severe thrombocytopenia that occurs in radiation-induced bone marrow suppression. PMID- 1410279 TI - Repopulation of O-2A progenitor cells after irradiation of the adult rat optic nerve analyzed by an in vitro clonogenic assay. AB - In the central nervous system (CNS) O-2A (Oligodendrocyte type 2 Astrocyte) progenitor cells have been proposed as potential target cells, and their depletion by irradiation will cause demyelination. The extent and time course of repopulation of these glial stem cells were studied in the adult rat optic nerve after irradiation in vivo. The number of O-2A progenitor cells was measured quantitatively by an in vitro clonogenic assay. Although the CNS is typically a late-responding tissue, repopulation was initiated almost immediately after irradiation and after several weeks a plateau was reached that lasted up to 6 months. Single doses of 4-12 Gy of X rays caused a permanent reduction in the number of O-2A progenitor cells. An analysis of the colony size of O-2A progenitor cells showed a sustained reduction in the number of offspring of cells surviving a dose of 12 Gy. In addition, the colony size of unirradiated progenitors diminished with increasing age of the animals. PMID- 1410280 TI - Identification of nitroxide radioprotectors. AB - The nitroxide Tempol, a stable free radical, has recently been shown to protect mammalian cells against several forms of oxidative stress including radiation induced cytotoxicity. To extend this observation, six additional water-soluble nitroxides with different structural features were evaluated for potential radioprotective properties using Chinese hamster V79 cells and clonogenic assays. Nitroxides (10 mM) were added 10 min prior to radiation exposure and full radiation dose-response curves were determined. In addition to Tempol, five of the six nitroxides afforded in vitro radioprotection. The best protectors were found to be the positively charged nitroxides, Tempamine and 3-aminomethyl PROXYL, with protection factors of 2.3 and 2.4, respectively, compared with Tempol, which had a protection factor of 1.3. 3-Carboxy-PROXYL, a negatively charged nitroxide, provided minimal protection. DNA binding characteristics as studied by nonequilibrium dialysis of DNA with each of the nitroxides demonstrated that Tempamine and 3-amino-methyl-PROXYL bound more strongly to DNA than did Tempol. Since DNA is assumed to be the target of radiation-induced cytotoxicity, differences in protection may be explained by variabilities in affinity of the protector for the target. This study establishes nitroxides as a general class of new nonthiol radioprotectors and suggests other parameters that may be exploited to find even better nitroxide-induced radioprotection. PMID- 1410281 TI - Radioprotection of DNA in isolated nuclei by naturally occurring thiols at intermediate oxygen tension. AB - Incubation of isolated Chinese hamster ovary cell nuclei, equilibrated in an atmosphere containing 2% O2, with glutathione, cysteine, or cysteamine resulted in a decrease in the number of X-ray-induced DNA double-strand breaks (DSBs), determined by pH 9.0 filter elution. In the absence of exogenous thiol, no sensitization was observed with the addition of N-ethylmaleimide, indicating that endogenous thiols were not present at significant levels. Protection by 0.3 mM glutathione was not enhanced by the addition of exogenous glutathione S transferases or by glutathione peroxidase. The data were analyzed according to a simple competition model with various hypotheses. Cysteamine was more than an order of magnitude more effective than the other thiols tested, on a molar basis, in preventing DSB formation. Depending on the hypothesis used to evaluate the data, glutathione was either much less effective, on a molar basis, in preventing the bulk of the DSBs or was capable of preventing only approximately 55% of the damage, regardless of concentration. These data suggest that natural thiols other than glutathione may contribute to cellular radioprotection even if their concentration is much lower than that of glutathione. The data also suggest that despite the relative inefficiency of glutathione as a radioprotector, some areas of oxygenated tissues--where the oxygen tension falls below 2%--may be protected by glutathione concentrations in the physiological range of 3-20 mM. PMID- 1410282 TI - [The functional status of the hypophyseal-adrenal cortical adaptation system in children in Byelarus living under the action of low doses of radiation after the accident at the Chernobyl Atomic Electric Power Station]. AB - The analysis of the status of sympatho-adrenal and hypophysis-adrenal medulla systems of adaptation in children living in territories contaminated by radionuclides was carried out. A decrease in the catecholamine level in children's urine and hyperactivity of the hormonal response of adrenal medulla to endogenous ACTH indicated the reduced ability of adaptation and decreased resistance of children's organisms to stress factors of the environment. PMID- 1410283 TI - [The effect of iodine-131 on the binding characteristics of sex and thyroid hormones by blood plasma proteins in children with a functional thyroid disorder as a result of the accident at the Chernobyl Atomic Electric Power Station]. AB - In studying characteristics of specific interaction of estradiol-, testosterone- and thyroid-binding blood globulins with the corresponding ligands in children from Gomel Province with endemic swelling of the thyroid gland (degrees I and II) affected by iodine-131 revealed were a reduced cooperativity in estradiol and T-3 binding and a halved affinity to androgens and thyroids as compared to healthy controls. In addition, there was a drastic decline in the binding capacity of estradiol- and testosterone-binding globulins in the blood plasma. The endemic thyroid gland swelling is supposed to be due to sexual malfunction in teenagers. PMID- 1410284 TI - [Radiation reactions and the possibilities for their modification in rats exposed in the area of the Chernobyl Atomic Electric Power Station]. AB - A study was made of some embryological, hematological, cytogenetic and biochemical characteristics in Wistar rats exposed within the Chernobyl NPP zone over a period of 30 days (the average radiation background level, 75, and at the soil surface, 115 mR/h; a cumulative dose, 57 rad/30 days, and for pregnant rats, 36 rad/20 days). The quantity of chromosome aberrations in bone marrow metaphases and the embryonal death rate were invariable; some cases of teratogenesis were, however, observed. The total number of karyocytes in the brain and the leukocyte content in the peripheral blood sometimes decreased. The changes in certain characteristics (such as the content of endogenous amines and thiols in the liver and spleen) of the endogenous radioresistance background (ERB) and the normalization of the ERB by the radioprotective agent MIGI-K were found. PMID- 1410286 TI - [The quantitative patterns in the yield of chromosome aberrations in a human lymphocyte culture under fractionated gamma-neutron irradiation at different stages of the mitotic cycle. The cytogenetic effects at the G0 stage]. AB - A study was made of the quantitative regularities of the interaction of cytogenetic damages induced, at the G0 stage of human lymphocyte culture, by fractionated gamma-neutron radiation, within a wide range of doses, delivered in the direct of reverse sequence at the intervals between fractions of 1 and 5 h. The results were compared with those obtained in experiments with single and fractionated gamma- or neutron irradiation within the same dose range. PMID- 1410285 TI - [Chromosome aberration induction in murine spermatocytes in joint exposure to radiation and sodium nitrite and nitrate]. AB - In studying the combined effect of single and fractionated exposure to gamma/neutron radiation (12.5-50 cGy) and sodium nitrite (100 mg/kg) and chronic irradiation with a mixture of radiation (25 cGy) and sodium nitrite, nitrate (10 100 mg/l) the synergistic effect was observed in inducing reciprocal translocations in mouse spermatocytes. The dose-response function of the reciprocal translocations occurrence in Af mouse spermatocytes was nonlinear; there was a "plateau" within the dose range from 25 to 50 cGy. PMID- 1410287 TI - [The role of the thyroid hormones in regulating chromosomal resistance to microwave exposure]. AB - The mutagenic effect of microwaves (2450 MHz, 500 mu W/cm2, 30 days, 7 h/day) on rats was shown to decrease under the influence of thyroxine (2.5 mu g/100 g) administered over a two-week period. The major role of thyroid hormones in the formation of the antimutagenic effect of nonionizing radiation (2450 MHz, 10 mu W/cm2, 30 days, 7 h/day) was confirmed by the experiments with the parathyroid gland being removed. PMID- 1410288 TI - [The inhibition by the tumor necrosis factor of the death and DNA fragmentation of lymphoid cells in irradiated rats]. AB - The influence of a tumor necrosis factor, administered 16 h before irradiation of rats, on the radiation response of thymus and bone marrow cells has been investigated. Three and 6 h after irradiation the following indices were analyzed: the number of apoptotic cells in the thymus; the accumulation of polydeoxyribonucleotides and the appearance of single-strand breaks in DNA of bone marrow and thymus cells; and the electrophoretic properties of thymocyte DNA. The injection of a tumor necrosis factor reduced the number of polydeoxyribonucleotides, inhibited internucleosome DNA fragmentation, and did not influence the formation of single-strand breaks in DNA. PMID- 1410289 TI - [The effect of one-time external gamma irradiation at different stages of ontogeny on the thyroid status of rats]. AB - A single external gamma-irradiation (1 Gy) of rats on day 35 of their life causes stable structural and functional disturbances in the thyroid gland leading to the development of hypothyrosis at the remote times following irradiation which is demonstrated by the decrease in the concentration of thyroxine in the blood, increase in the thyrotropic function of the hypophysis and inhibition of the activity of tyrosine-dependent enzyme, alpha-glycerophosphate dehydrogenase, in the liver. Disturbances induced by such exposure in the thyroid gland of adult rats are insignificant and compensatory in time. PMID- 1410290 TI - [The effect of gamma irradiation at sub- and supralethal doses on the lipid composition of the mucosa and of the brush border membrane of the small intestine in rats]. AB - A study was made of the amount of cholesterol and its ethers (phosphatidyl choline, phosphatidyl ethanolamine, sphingomyelin, phosphatidyl serine, and phosphatidyl inositol) in mucosa and membrane of the small intestine brush border 24 h after 4 Gy and 2 h after 20 Gy irradiation. No changes in the lipid content of mucosa and membrane of the brush border were noted after 4 Gy irradiation. Exposure to 20 Gy radiation doubled the number of cholesterol ethers and made the number of individual phospholipids and cholesterol increase by nearly 1.5 times. The amount of phosphatidyl serine in the brush border membrane increased by almost 3 times; the concentration of other lipids increased by nearly 1.5 times; cholesterol/phospholipid ratio was unchangeable. PMID- 1410292 TI - [The effect of ionizing radiation on nitrosamine formation from anthropogenic precursors]. AB - The kinetics of formation of nitrosoamines from precursors under the effect of ionizing radiation has first been quantitatively estimated, and the optimal conditions of their formation determined. The possibility of formation of nitrosoamines under the effect of low-level radiation has been investigated. Using the mathematical functions obtained from the experiments, the number of nitrosoamines, that may form under the effect of radiation in the aqueous medium, has been determined. PMID- 1410291 TI - [The individual postradiation reactions of cyclic nucleotides in the lymphoid cells of the rat spleen]. AB - X irradiation (4.3 Gy) of rats was shown to cause different reactions of the cyclic nucleotide system in differently reactive animals which was determined by the neutrophilic response in the peripheral blood after three-hour immobilization. Changes in the cyclic nucleotide content and in the activity of adenylate cyclase were found to occur in both hyper- and hyporeactive animals 24 h after irradiation. In hyperreactive animals, however, these changes were more pronounced: a relative ability of adenylate cyclase to be activated in hyperreactive animals made 30%, and 52% in hyporeactive animals. The cAMP content in lymphocytes of the spleen of hyporeactive rats was twice as high as that in hyperreactive animals. PMID- 1410293 TI - [The effect of ionizing radiation at superhigh doses on the processes of dopamine release and reuptake by nerve endings in different sections of the brain]. AB - Rats exposed to fast 24 MeV electrons (100 Gy) at the state of early transient incapacity (ETI) exhibited active release and reuptake of dopamine in nerve terminals of the striatum. No changes in the indices under study were found in rats exposed to 25 Gy radiation that did not cause the ETI development. The in vitro irradiation of the isolated synaptosomes (100 Gy) inhibited dopamine reuptake and increased the number of sites of 3H-spiperone binding to D2 receptors in a membrane fraction isolated from the striatum. PMID- 1410294 TI - [Changes in cellular radiosensitivity by modifying the cytoplasmic membranes]. AB - The radiosensitivity of mouse myeloma and E. coli cells in the presence of Mg2+ and UO2(2+) ions has been investigated. It has been shown that Mg2+ ions (10(-4) M) do not influence the viability of E. coli and mouse myeloma cells. The presence of Mg2+ ions during irradiation reduces the survival rate of E. coli cells, but the addition of Mg2+ ions after irradiation does not influence the radiosensitivity of E. coli cells. Comparison of the results on the influence of Mg2+ ions upon cells and bilayer lipid membranes (BLM) permits us to suppose that Mg2+ ions increase the positive charge of the membranes thus promoting the increase in the number of short-lived radiolysis products which impair membranes and increase cell radiosensitivity. UO2(2+) ions (10(-4) M) increase the radioresistance of E. coli cells which can be associated with the increase in the lateral membrane viscosity, as it was shown in the studies on BLM. PMID- 1410295 TI - [The effect of the immunomodulator glucosaminylmuramyl dipeptide on hematopoiesis in mice with experimental cytopenia]. AB - Simulation of cytopenia by injection of cyclophosphamide (100 mg/kg) or by exposure to ionizing radiation (4 Gy) was shown to cause in mice similar, by the severity and rate of development, transient inhibition of haemopoiesis which was somewhat more persistent after irradiation. Glucosaminylmuramyl dipeptide applied after the above effects promoted the haemopoiesis recovery. PMID- 1410296 TI - [The effect of gas hypoxia (10% O2) and dextran sulfate on the radiosensitivity of the stem cells of the intestinal epithelium in mice]. AB - Injection of dextran sulphate before irradiation was shown to protect jejunal epithelium stem cells (D0 increased from 1.13 to 1.82 Gy). The protective effect of a combination of dextran sulphate and gas hypoxic mixture (10% O2) did not exceed that of the administration of the gas hypoxic mixture (10% O2) alone. PMID- 1410297 TI - [The circadian oscillations in the radioresistance of the CNS in female and male rats after craniocaudal gamma radiation]. AB - In experiments with albino mongrel male and female rats subjected to craniocaudal gamma irradiation (60Co, 62.5 Gy), daily oscillations of the CNS radioresistance were revealed by the criterion of occurrence of early transient neurological disorders (ETND). Experiments were conducted during two seasons (January and April). The time factor was significant, as estimated by the frequency and severity of opisthotonos and convulsions in males. ETND were more frequent and severe in females than in males. PMID- 1410298 TI - [The effect of gamma irradiation on the direct intercellular interaction (rosette formation) of thymic macrophages with thymocytes]. AB - In experiments with (CBA x C57BL/6)F1 mice, the effect of radiation on rosette formation between thymus macrophages (Th-MPh) and thymocytes (Thc) was studied on days 1, 4, 12, 30, and 60 following gamma irradiation with doses of 0.5, 2, 4, and 8 Gy. The influence of supernatants of thymus epithelial cells (EC) on the rosette formation was estimated. Gamma irradiation with doses of above 2 Gy was shown to cause a dose-dependent inhibition of rosette formation of Th-MPh with Thc in vitro. Recovery of rosette-forming ability of Th-MPh was observed on day 60 of the experiment. Two types of rosette-forming Th-MPh were identified: RFMPhII with low rate of binding to Thc and RFMPhII with high rate of binding to Thc. Radiation affects mainly the RFMPhII content. With radiation doses of 4 and 8 Gy no complete restoration of RFMPhI was observed on day 60. The total population of rosette-forming Th-MPh was restored on day 60 mainly due to cells with low rate of rosette formation. The EC supernatant promoted rosette formation of exposed Th-MPh with Thc. The effect was maximum at early times following irradiation of Th-MPh with a dose of 4 Gy. PMID- 1410299 TI - [The distribution of intratracheally administered plutonium-239 throughout the skeletal bones]. AB - The data are presented on distribution of the intratracheally administered plutonium-239 within the skeleton bones. Plutonium was found to be distributed non-uniformly within the skeleton: it was concentrated mainly in the bones where the trabecular fraction of the bone tissue was most manifest. The results obtained were supported by the correlation analysis. PMID- 1410300 TI - [The effect of ionizing radiation on the vascular bed of the skin in ontogeny. The function of the microcirculatory bed of the skin in the fetuses of white rats sublethally irradiated]. AB - Albino female rats were exposed to X radiation (5 Gy, 180 kV, 10 mA, filter 0.5 mm Cu) on days 10-15 of pregnancy. After 3 and 7 days they were sacrificed (under ether anesthesia) and fetuses were extracted. The status of the lympho- and hemomicrocirculatory beds (LMCB and HMCB) of the fetus back skin was studied by the macro- and microscopic methods. As early as day 3 of radiation sickness the diameter of LMCB vessels increased by 1.4-1.9 times, whereas changes in GMCB were less pronounced. On day 7, there was a progressive increase in dilatation of LMCB vessels, alongside with the narrowing of large units (arteries and veins). The development of the connective framework of the fetus skin was retarded. PMID- 1410301 TI - [Further comment on the problem of low doses in radiobiology]. PMID- 1410302 TI - Occupational lung disease. PMID- 1410303 TI - Clinical overview of occupational lung disease. AB - The workplace has been a source of lung injury for centuries, yet awareness of the types of injuries has varied over time. Because of distinctive differences among the occupational lung disorders, a continual update of the clinical findings, dose response data, physiologic characteristics, and radiographic findings is needed. The radiologist plays a key role for the evaluation of miners, foundry or factory workers exposed to mineral dusts, and of workers exposed to the "biologic" dusts, infectious agents, cancer causing agents, and chemicals causing interstitial lung diseases. This overview includes a discussion of classification systems, criteria for diagnosis of occupational lung diseases, the pulmonary clinician's evaluation, and important aspects of specific disorders and concludes with a discussion of pulmonary disability determination. PMID- 1410304 TI - The 1980 ILO classification of radiographs of the pneumoconioses. AB - The 1980 ILO classification of radiographs of the pneumoconioses has undergone revision and improvement in response to increases in knowledge and international concerns. Its goal is to standardize the reading and reporting of radiographic manifestations of the inhalation of dust so that international epidemiologic comparisons are possible. It remains an imperfect instrument, but "... although total elimination of variation is impossible, some measure of control can be achieved." PMID- 1410305 TI - Standard imaging in silicosis and coal worker's pneumoconiosis. AB - Silicosis and coal worker's pneumoconiosis (CWP) are two relatively common occupational diseases. Silicosis is the most common pneumoconiosis in the United States. It results from inhalation of the particulate form of quartz or other crystalline forms of silicon dioxide with a diameter of less than 5 micrograms. CWP is the result of inhalation of carbon particles. Pathologic features of the two diseases differ, yet their radiologic features are identical. Simple pneumoconiosis is characterized by multiple small rounded opacities of 1 to 5 mm in diameter and with a bias for the upper lung zones. Complicated pneumoconiosis results from confluence of small opacities into large opacities that form conglomerate masses or progressive massive fibrosis. PMID- 1410306 TI - Computed tomographic evaluation of silicosis and coal workers' pneumoconiosis. AB - The introduction of computed tomography (CT) has modified the radiologic approach to silicosis and coal worker's pneumoconiosis considerably, allowing earlier recognition and more precise characterization of pulmonary abnormalities than chest radiography. An optimal approach to CT recognition requires an understanding of the main physiologic and pathologic features that are known to occur in both pneumoconioses. This report focuses on the most common CT features of simple and complicated forms of silicosis and coal worker's pneumoconiosis as well as on the optimal scanning protocol. The respective roles of chest radiographs and CT scans in the recognition of pneumoconiosis and follow-up of exposed workers are discussed. PMID- 1410307 TI - Conventional radiography in the diagnosis of asbestos-related disease. AB - Standard chest radiography, despite its limitations, remains an important means of evaluating the asbestos-exposed worker. Because of its wide availability, low radiation dose, and low cost, it will continue to be the standard imaging procedure for the screening of asbestos-exposed populations. PMID- 1410308 TI - Computed tomography in the evaluation of benign asbestos-related disorders. AB - High-resolution CT is more sensitive than chest radiography and conventional CT in the detection and assessment of benign asbestos-related pleural and parenchymal diseases. The HRCT features of asbestosis correlate with clinical and functional restriction. The specificity of HRCT findings of asbestosis needs further evaluation. Given its low cost and availability, chest radiography remains the mainstay of imaging in benign asbestos-related diseases. CT (conventional or high-resolution) is not recommended as a universal screening test in asbestos-exposed workers. It has a useful role in identifying and quantitating pulmonary fibrosis distinct from emphysema and pleural disease, in distinguishing pleural disease from normal extrapleural soft tissues, and in clarifying the confusing chest radiograph or conflicting pulmonary function data. CT is useful in excluding a mass that may be obscured by extensive pleural and parenchymal fibrosis and is helpful in the follow-up of benign fibrotic masses or in the direction of their biopsy. PMID- 1410309 TI - Chronic beryllium disease. AB - Chronic beryllium disease is a multisystem granulomatous disease caused by industrial exposure to beryllium dust or fumes. It is thought to represent a hypersensitivity disorder rather than a true pneumoconiosis. The lung is the primary organ of involvement, and many of the radiographic features resemble sarcoid. PMID- 1410310 TI - Hypersensitivity pneumonitis. AB - Hypersensitivity pneumonitis is an immunologic mediated response in the lung to inhaled organic antigen. Farmer's lung and pigeon breeder's lung are the two most widely know disorders. The chest radiograph usually is normal in hypersensitivity pneumonitis. When abnormal, the distribution of disease favors the lung bases with acute disease and the upper lung zones with chronic disease. Computed tomography (CT) may be more sensitive in detecting parenchymal abnormalities, although the characteristic findings of hypersensitivity pneumonitis at CT or high-resolution CT are nonspecific. PMID- 1410311 TI - Chemical pneumonitis. AB - Many organic and nonorganic agents can cause chemical pneumonitis. The more soluble agents tend to involve the upper respiratory tract, whereas less soluble agents reach the distal airways, causing pulmonary edema. The initial chest radiograph can be normal for as long as 48 hours, therefore delayed radiographs are important in significant exposures. The most common radiographic pattern is pulmonary edema, although various radiographic opacities have been reported. Acute complications include secondary pneumonia. Long-term complications include bronchiectasis, bronchiolitis obliterans, and lung destruction. PMID- 1410312 TI - Occupationally induced neoplasms of the lung and pleura. AB - The relationship between asbestos and mesothelioma has been well delineated in the past. The epidemiologic, clinical, radiologic, and pathologic features of mesothelioma are discussed with reference to the diagnostic evaluation of asbestos-exposed patients. The extensive epidemiologic data correlating asbestos, tobacco smoke, and induction of lung carcinoma are also reviewed. These data provide a model for evaluation of other occupationally induced lung carcinogens such as organic and metallic industrial inhalants. PMID- 1410313 TI - Alternate AP knee method assures open joint space. AB - An alternate method of imaging the knee in the AP projection assures diagnostic joint spaces to provide optimal diagnostic information. The degree of angulation is varied from 5 degrees cephalic to 5 degrees caudal and is determined by measuring the patient's anterior superior iliac spine to table-top distance. PMID- 1410314 TI - A comparison of student radiographic reject rates. AB - Educators and administrators often are called upon to estimate the economic considerations of students in radiology departments for clinical education. Yet, little has been written about student radiographic reject rates. This study assessed the radiographic reject rate of 320 first- and second-year students from 21 hospital- and college-sponsored programs in 18 states. PMID- 1410315 TI - Task analysis provides data for MRI curriculum planning. AB - No standardized education or training program currently exists for magnetic resonance imaging technology. The results of this initial national task analysis will assist in development of a curriculum guide and serve as a baseline for further research. PMID- 1410316 TI - TIPSS: use of metallic stents offers non-surgical alternative. AB - Transjugular intrahepatic portosystemic stent shunts (TIPSS) procedures can be a significant non-surgical treatment for patients with liver cirrhosis, portal hypertension and at least one episode of bleeding from gastroesophageal varices. This article presents an in-depth description of the TIPSS procedure and reports results obtained from 15 attempted TIPSS cases. PMID- 1410317 TI - Things happen to the best of us. PMID- 1410318 TI - Patient care is what it's all about. PMID- 1410319 TI - Profits, drugs and wellness programs. PMID- 1410320 TI - [The work of the Hessian Medical Office]. AB - The task of this committee on quality control and radiation protection is described, along with an explanation of the legal principles used in the execution of its duties (Nuclear Safety Law and Radiological Ordinance). Furthermore, the procedures used for the evaluation of X-rays are illustrated, followed by test films of X-ray equipment and film developers. Finally, the composition and activities of the Radiation Protection Committee are described. PMID- 1410321 TI - [Quality assurance in radiology from the viewpoint of the specialists and the supervisory authorities]. AB - Quality assurance for diagnostic imaging equipment has been successful so far. In the old Federal Republic of Germany, inspection of the existing equipment in diagnostic radiology in being completed. The estimated number of uninspected units is relatively small. All detected shortcomings have been repaired in the meantime, and very few faults have been detected in newly installed equipment. Of the status obtained following inspection and repair is to be maintained, however, more effective methods must be implemented. There is no doubt that everybody involved in quality assurance programs, including the experts and supervisory authorities, is actively working on improving the results. PMID- 1410322 TI - [Quality assurance from the viewpoint of the x-ray film industry]. AB - The parameters of a film-screen-combination are listed in the directive to section 16 of the german X-ray Regulation. These parameters are determined by methods described in DIN standards and published by the manufacturer. Comparable but less precise parameters are determined in the Acceptance Test. For physical reasons it is not possible to determine the speed of an X-ray film or the intensification factor of a screen separately. The films, screens and processing chemicals delivered by the members of the manufacturer association ZVEI are kept below a deviation (expressed as relative contribution to the system speed S) of +/- 10% for the majority of products, the upper limit is +/- 15%. Poor storage and transport conditions may adversely affect the quality of X-ray films. A special labeling of the film box shall serve to guarantee safe distribution channels. The processing conditions are adjusted at the Acceptance Test according to the manufacturers recommendations. The Constancy Test of film processing serves to maintain these correct conditions. Methods deviating from the DIN method are of limited (Bayerische method) or no value (Stuttgart method). PMID- 1410323 TI - [Evaluation of different methods of control of film processing]. AB - In addition to the official control method (DIN 6868), alternative test methods have been developed in the last few years: the "visuelle Methode" by Eder and the "Stuttgarter Modell." The aim of both methods is mainly to increase practicability and economy. The DIN method, however, demonstrates clear benefits, precision, practicability and economy, and it is the only method that allows a trend analysis at small intervals, which is the basis for possible preventive action. PMID- 1410324 TI - [Sources of error in the quality assurance of x-ray equipment]. AB - With the introduction of the German industrial protocol for quality assurance of X-ray equipment, everybody using X-ray machines fell into some sort of trap or found some of the procedures misleading. Vigorous discussions were held on every conceivable aspect of this and other protocols, and are still in progress. This paper points out some of the common traps and considers a new type dosimeter, which allows a definite separation of quality assurance of X-ray equipment and of processing and which can also be used in future for quality assurance of digital radiography equipment. PMID- 1410325 TI - [MR tomographic aspects of olivary pseudohypertrophy]. AB - MRI aspects of olivary pseudohypertrophy (OH) following pontocerebellar lesions of different etiology and localization are reviewed. OH is characterized by unilateral or bilateral enlargement of the inferior olivary nucleus and increased signal intensity in T2- and, especially, in proton-density (PD)-weighted images. Correlations between the extent and the uni- or bilateral presence of olivary hypertrophy and the localization of the primary pontocerebellar lesions are discussed. PMID- 1410328 TI - [Para- and non-ethical publication practices in medicine]. PMID- 1410326 TI - [Iotrolan versus iopamidol. A controlled double-blind study with lumbar myelography]. AB - Within the frame work of lumbar myelography, 158 patients were entered in a double-blind study in order to test a dimeric contrast medium (iotrolan) against a monomeric one (iopamidol), both of them non-ionic. A three-step scheme was applied to evaluate the X-ray pictures with respect to contrast quality. Particular attention was paid to the visibility of details, i.e. the nerve root and its course, as well as to how well it could be distinguished in the nerve root sheath. On the basis of a high level of significance (P less than 0.05), comparison of the two contrast media showed no difference in contrast quality. Sixty-nine percent of the examinations using iotrolan resulted in excellent contrast quality, whereas the corresponding very good results using iopamidol lay at 76%. Twenty-nine percent of the patients examined with iotrolan and 27% of those examined with iopamidol showed side effects. Headache occurred most frequently, followed by nausea, dizziness and neck pain. Sixty percent of the patients suffering from postmyelographic reactions reported delayed headache, which occurred most often with iotrolan rather than iopamidol. As for manifestation of other postmyelographic side effects, there were no significant differences (P less than 0.05, Fischer's test) between the two groups of contrast media. PMID- 1410327 TI - [Ganglioneuroma of the pelvis accompanying pregnancy]. AB - Ganglioneuroma is an uncommon benign tumor of the sympathetic nervous system. In most cases it originates from the thoracic or lumbar portion of the gangliated cord or from the medulla of the suprarenal glands. It is the differentiated form of malignant neuroblastoma. The tumor often manifests itself in young adults by displacement of the surrounding structures. In the case presented the special diagnostic problems of locating the tumor in the pelvis in early pregnancy are discussed. PMID- 1410329 TI - [An unclear space-occupying lesion in the portocaval space. A hypertrophied papillary process in the caudate lobe of the liver]. PMID- 1410330 TI - [Importance of MR-mammography. Satellite symposium following the 73rd German Radiology Congress. Wiesbaden, 27 May 1992]. PMID- 1410331 TI - [7th expert's exchange in contrast media preparation and after care, "Good Clinical Practice". Lindau/Bodensee, 9-12 April 1992]. PMID- 1410332 TI - Gastrointestinal tract in the immunocompromised host: opportunistic infections and other complications. AB - In the decade since the early 1980s, the increasing use of immunosuppressive therapy for cancer and autoimmune disease, as well as for organ transplantation, has combined with the acquired immunodeficiency syndrome epidemic to increase greatly the incidence of opportunistic infections and other complications of the gastrointestinal tract. Consequently, barium fluoroscopic and cross-sectional imaging studies tailored to address these problems are no longer uncommon. Although overlap exists, there are radiographic patterns that can direct the diagnosis to an opportunistic infection and sometimes to a specific pathogen. This article describes and illustrates the radiographic findings of gastrointestinal superinfection with Candida albicans, cytomegalovirus, Cryptosporidium spp, herpes simplex virus, Mycobacterium tuberculosis, M avium intracellulare, and human immunodeficiency virus. Other gastrointestinal tract complications of immunosuppression are discussed, including graft-versus-host disease following bone marrow transplantation, typhlitis, and pseudomembranous colitis. PMID- 1410333 TI - Fine-needle aspiration and flow cytometry for evaluation of primary breast cancer. PMID- 1410334 TI - MR imaging differentiation of adrenal masses: has the time finally come? PMID- 1410335 TI - Acute appendicitis in childhood: the role of US. PMID- 1410336 TI - Diagnosis of uterine anomalies: relative accuracy of MR imaging, endovaginal sonography, and hysterosalpingography. PMID- 1410337 TI - Benign adrenocortical masses: diagnosis with chemical shift MR imaging. AB - Benign adrenocortical masses often contain lipid; metastases and pheochromocytomas do not. Standard and lipid-sensitive (chemical shift) magnetic resonance (MR) images of the adrenal glands in 31 patients with 45 adrenal masses were reviewed to determine if simple visual analysis of these images would increase diagnostic specificity. Lipid was considered present if signal intensity of the adrenal mass relative to other tissues decreased on chemical shift images relative to comparable standard images. Both myelolipomas and 26 of 27 benign cortical masses displayed a loss of signal intensity on at least one chemical shift image; all 12 metastases, the three hemorrhages, and a cyst did not. Opposed-phase images were slightly more sensitive than fat-suppressed images in depicting lipid within benign cortical masses. All masses had higher signal intensity than that of the liver on standard T2-weighted MR images. Chemical shift MR imaging can demonstrate lipid within benign adrenocortical masses and thus increase specificity, potentially obviating biopsy and aggressive follow-up. PMID- 1410338 TI - Male infertility: role of transrectal US in diagnosis and management. AB - Ultrasound (US) has become crucial in the assessment of infertility of couples, in 50% of whom the male partner is responsible. Male infertility is caused by many diverse conditions, from reparable obstructive disorders to noncorrectable intrinsic testicular failure. During the past 4 years, a select group of 70 young infertile men with azoospermia or oligospermia and low ejaculate volume were examined with transrectal US. Twenty-six patients had congenital bilateral absence of the vas deferens, 11 had congenital unilateral absence of the vas deferens and contralateral obstructive pathology, 15 had additional abnormalities thought to be directly related to semen deficiencies, and 18 patients with other causes for semen deficiency and infertility had findings that were either normal or showed minor abnormalities. The delineation of congenital and obstructive abnormalities of the distal urogenital tract with transrectal US enables an accurate diagnosis of certain cases of male infertility and helps guide appropriate clinical and surgical management. PMID- 1410339 TI - Transrectal US in evaluation of patients after radical prostatectomy. Part I. Normal postoperative anatomy. AB - The appearance of the prostatic fossa on transrectal ultrasound (TRUS) scans obtained after radical retropubic prostatectomy (RRP) was studied in 25 patients believed to have no tumor on the basis of their level of serum prostate-specific antigen (PSA) (< or = 0.4 ng/mL). The profile of the vesicourethral anastomosis (VUA) in the midsagittal plane was tapered in 13 patients (52%) and nontapered in 12 patients (48%). The nontapered profile was associated with incontinence in nine of 11 patients (82%) followed up for less than 12 months but in only four of 14 patients (28%) followed up beyond 1 year. In 20 patients (80%), a hypoechoic soft-tissue lesion (average volume, 1.7 cm3) was seen anterior to the VUA and indented the anterior bladder wall. The length of the urethral high-pressure zone increased with muscular contraction of the pelvic floor. Knowledge of the baseline anatomic structures depicted on TRUS scans obtained after RRP may be useful in selection of tissue for TRUS-guided needle biopsy in patients with elevated levels of PSA. The many post-surgical changes reduced the specificity of the TRUS findings. PMID- 1410340 TI - Seminal vesicles: biopsy-related hemorrhage simulating tumor invasion at endorectal MR imaging. AB - The diagnosis of seminal vesicle invasion by prostatic carcinoma is based on observation of foci of relatively decreased signal intensity on T2-weighted magnetic resonance (MR) images. Similar findings were observed in the absence of tumor invasion in nine patients who had recently undergone prostatic needle biopsy. Noncorresponding foci of abnormally increased signal intensity were also present on T1-weighted images in eight patients. These signal intensity abnormalities were of variable location and extent, and usually did not follow the expected pattern of spread from the primary prostatic tumor site. Radical prostatectomy in all patients showed the seminal vesicles to be normal. Signal intensity patterns observed on MR images appear to represent hemorrhagic breakdown products related to prostatic needle biopsy, which may result in direct trauma to the seminal vesicles. Another potential mechanism is retrograde transport of blood products from the site of prostatic biopsy to the seminal vesicles via the ejaculatory ducts. Awareness of this phenomenon will assist in accurate interpretation of MR images for staging of prostate cancer. PMID- 1410341 TI - Transvaginal US-guided aspiration of ovarian cysts and solid pelvic masses. AB - Sixty-eight transvaginal ultrasound (US)-guided aspirations or biopsies were performed in 61 patients, of whom 48 had ovarian cysts and 13 had solid pelvic masses. In one patient with an ovarian cyst, aspiration revealed malignancy. Thirty-six of the 48 cysts were drained transvaginally in 23 premenopausal and 13 postmenopausal women, with recurrence rates of 48% and 80%, respectively. In seven cases a cyst was aspirated twice. In the 13 patients with solid pelvic lesions, 11 lesions proved to be malignant, with positive biopsy results in nine (sensitivity, 82%). Two benign lesions were correctly identified. No major complication was observed. The authors conclude that the transvaginal route offers simple access to pelvic lesions in pre- and postmenopausal patients. For women with a solid pelvic lesion, transvaginal aspiration biopsy with endovaginal US guidance is a safe and effective alternative to surgery, especially for patients with previously diagnosed malignant disease. PMID- 1410342 TI - Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique--comparison with pulmonary angiography. AB - Forty-two patients were prospectively evaluated with spiral volumetric computed tomography (CT) and selective pulmonary angiography of each lung to detect central pulmonary thromboembolism. Spiral volumetric CT images obtained with either 90 mL of 30% contrast material or 120 mL of 12% contrast material were graded as excellent or good in 98% of the examinations (41 patients). Diagnosis of pulmonary embolism with spiral volumetric CT was based on the direct visualization of intraluminal clots: partial filling defects (n = 41; 37%), complete filling defects (n = 51; 46%), "railway track" signs (n = 6; 5%), and mural defects (n = 14; 12%). All 23 patients with normal findings of spiral volumetric CT had normal findings of pulmonary angiography. With spiral volumetric CT, the finding of 112 central emboli (eight main, 28 lobar, and 76 segmental) corresponded exactly to the angiographic findings, but nine intersegmental lymph nodes were erroneously interpreted as filling defects. In one case of normal pulmonary angiographic findings, asymmetry in pulmonary arterial perfusion was misinterpreted as pulmonary embolism with spiral volumetric CT. Spiral volumetric CT can reliably depict thromboemboli in second- to fourth-division pulmonary vessels. PMID- 1410343 TI - Intersegmental (intersublobar) septum of the lower lobe in relation to the pulmonary ligament: anatomic, histologic, and CT correlations. AB - A thin horizontal linear area of hyperattenuation that extends laterally from the mediastinal surface of the lung within the area between the inferior pulmonary vein and the diaphragm is a common observation on computed tomographic (CT) scans of the chest. To determine the anatomic basis for this structure, the authors examined four normal human lungs (two right and two left lungs) fixed in an inflated state at pathologic and histologic examination and at CT. The structure in question was identified in one right and two left lungs. The linear area of hyperattenuation seen at CT is a septum of thin, loose intraparenchymal connective tissue that is bounded medially by the base of the pulmonary ligament, where the two sleeves of the visceral pleura appose one another, and laterally by a vertically oriented vein. The septum was identified in 39 of 50 (78%) normal chest CT scans. The pulmonary ligament often appeared to look like a beak at the mediastinal side of the lung. The septum, when visible (n = 39), was bounded medially by the beak in 28 CT scans (72%) and laterally by a vein in 24 scans (62%). PMID- 1410344 TI - ACR-NEMA digital imaging communication standard: demonstration at RSNA '92 infoRAD. PMID- 1410345 TI - Omental flap in lung transplantation. AB - Some surgeons performing lung transplantation will wrap the bronchial anastomosis with omentum in an attempt to improve healing. The authors retrospectively reviewed the chest radiographs and computed tomographic (CT) scans of 31 patients who underwent lung transplantation with bronchial omentopexy to determine the CT appearance of the intrathoracic omentum and the frequency and type of chest radiographic manifestations created by the omental flap. The omental flap was seen at CT in all patients, was predominantly of fatlike attenuation, and contained linear areas of increased attenuation representing omental vessels. In 16 patients (52%), a total of 29 chest radiographic findings that corresponded to the omental flap were seen. There was no statistically significant correlation between the type of operative procedure and the presence of a chest radiographic correlate for the omentum. The results showed that the omental flap is a potential diagnostic pitfall on post-lung transplantation chest radiographs; when there is confusion, however, the omentum can be identified with CT because of its attenuation value and characteristic course. PMID- 1410346 TI - Silicone breast implants in vivo: MR imaging. AB - This study was designed to evaluate pulse sequences and patient positioning for MR imaging of silicone breast implants in patients. One hundred forty-three patients (281 silicone implants) underwent imaging over a 21-month period. The combination of a T2-weighted fast spin echo technique (SE), T2-weighted fast SE with water suppression, and T1-weighted SE with fat suppression is recommended to reliably differentiate silicone from other breast tissues and to identify intracapsular and extracapsular ruptures or leaks. Seventy of the 143 patients underwent removal of their silicone implants. The sensitivity for detection of silicone implant rupture was 76%, with a specificity of 97%. Positioning the patient prone improved image quality. PMID- 1410347 TI - Nonpalpable breast microcalcifications: frequency, management, and results of incisional biopsy. AB - In a series of 500 consecutive needle localizations, there were 165 biopsies for benign microcalcifications without a mass. An incisional biopsy was performed in 49 of these cases (30%). Follow-up mammograms were available for review in 39 of the cases. The average length of follow-up was 32 months. In no case did malignancy develop at the biopsy site. When an incisional biopsy is performed, careful follow-up mammography is an alternative to a repeated needle localization and biopsy in selected cases. PMID- 1410348 TI - Schistosomiasis involving the breast. AB - A case of ectopic granulomatous schistosomiasis involving the breast is reported. Although schistosomiasis can involve almost any organ, involvement of the breast is very rare; to the authors' knowledge, there have been only three previously reported cases of breast involvement in the literature. This case was discovered at routine screening mammography. Innumerable, segmentally distributed, fine calcifications and mild architectural distortion were seen at mammography, and a biopsy was performed to exclude malignancy. There appears to be no way to accurately discriminate this disease from breast cancer before biopsy. PMID- 1410349 TI - Radiation therapy of cancer in prosthetically augmented or reconstructed breasts. AB - The authors review the literature and report their experience with radiation treatment of 39 prosthetically augmented or reconstructed breasts in 37 patients with primary or recurrent breast cancer. Group 1 consisted of 10 patients (12 primary breast cancers), of whom six had undergone previous breast augmentation and were later treated with lumpectomy and radiation therapy. Four patients were treated with mastectomy, reconstruction, and postoperative irradiation. Local tumor control was achieved in all patients. Excellent or good cosmetic results were achieved in all but two patients. Group 2 consisted of 27 patients with recurrent breast cancer after mastectomy and reconstruction. Local tumor control was achieved in 78% (21 of 27), with a mean duration of 34 months. Excellent or good cosmetic results were achieved in 93% (25 of 27). Patients who develop primary or recurrent breast cancer in prosthetically augmented or reconstructed breasts can be offered radical radiation therapy, with satisfactory tumor control and aesthetic results. PMID- 1410350 TI - Coronary artery calcification detected with ultrafast CT as an indication of coronary artery disease. AB - To assess the relationship of coronary artery calcification to angiographically detectable disease, the authors evaluated 100 patients less than 60 years of age who underwent clinically indicated coronary angiography and ultrafast computed tomography (CT). The ultrafast CT technique consisted of 3-mm-thick contiguous sections and a 100-msec acquisition time. All patients with clinically significant disease at angiography (defined as at least one stenosis with a diameter narrowing of at least 50%) had some coronary artery calcification present at ultrafast CT (100% sensitivity in this population). The absence of calcification at ultrafast CT had a 100% negative predictive value for clinically significant coronary artery disease. Specificity and positive predictive value were 47% and 62%, respectively. Sensitivity and specificity of ultrafast CT in the detection of patients with angiographically detectable disease were 94% and 72%, respectively. Ultrafast CT of the heart is an anatomically based, noninvasive test with high sensitivity for the detection of coronary artery calcification. Ultrafast CT may be beneficial in the screening of selected populations for the presence of atherosclerotic coronary disease. PMID- 1410351 TI - MR imaging of hypertrophic cardiomyopathy. AB - To assess the capability of magnetic resonance (MR) imaging to define the presence, distribution, and severity of the hypertrophic process, MR imaging was performed in 20 patients with hypertrophic cardiomyopathy and in five healthy volunteers. Among the 20 patients, 13 were classified as having asymmetric septal hypertrophy and seven as having apical hypertrophy. The mean myocardial thickness in the four-chamber view obtained in end diastole in asymmetric septal hypertrophy was 23.5 mm +/- 6.8 (mean +/- standard deviation) in the basal septum; the ratio of septal to posterolateral wall thickness was 2.05 +/- 0.44 (P < .05); those values were 10.4 mm +/- 2.7 and 1.01 +/- 0.19, respectively, in five healthy volunteers. The mean myocardial thickness in apical hypertrophy was 25.3 mm +/- 4.1 in the apex, and the ratio was 2.21 +/- 0.51 (P < .05); these values were 9.6 mm +/- 1.5 and 0.95 +/- 0.17, respectively, in five healthy volunteers. Three different subtypes of hypertrophic cardiomyopathy - resting obstructive (n = 5), latent obstructive (n = 3), and nonobstructive (n = 5) - were classified according to findings at catheterization in the 13 patients with asymmetric septal hypertrophy. PMID- 1410352 TI - Gastrointestinal hemorrhage in AIDS: arteriographic diagnosis and transcatheter treatment. AB - The usefulness of arteriography and transcatheter treatment was studied in nine patients with gastrointestinal hemorrhage and acquired immunodeficiency syndrome (AIDS). Selective arteriography was performed in all patients; transcatheter treatment was performed by means of embolotherapy or selective vasopressin infusion. Medical records were reviewed to determine the cause of hemorrhage and clinical outcome. Arteriography enabled identification of the site of hemorrhage in seven patients. Hemorrhage was caused by Kaposi sarcoma (n = 2), cytomegalovirus colitis (n = 1), lymphoma (n = 2), or unknown causes (n = 4). Neovascularity and dense parenchymal stain were present in patients with Kaposi sarcoma. Transcatheter treatment consisted of embolization (n = 3), vasopressin infusion (n = 2), or both (n = 1). Hemorrhage was controlled in six cases in which transcatheter treatment was administered. Complications included thrombosis of the femoral artery in a 7-month-old infant and formation of a pseudoaneurysm of the femoral artery, which was treated successfully with ultrasound-guided compression. In patients with AIDS and profuse gastrointestinal hemorrhage, arteriography often enables identification of a specific site of hemorrhage, which can be stopped with transcatheter treatment. PMID- 1410353 TI - Nitrogen-filled liposomes as a vascular US contrast agent: preliminary evaluation. AB - Liposomes with a mean diameter of 1-2 microns were made to entrap nitrogen gas and tested as an ultrasound (US) contrast agent. The gas-filled liposomes, or Aerosomes (ImaRx Pharmaceutical, Tucson) were tested in vitro for size, stability, reflectivity, and acoustic characterization, and were tested in vivo for acute toxicity in mice and for cardiac imaging in rabbits after intravenous injection. Aerosomes have much greater reflectivity and higher attenuation than do standard liposomes and retain their acoustic properties after storage in aqueous media for several months. The interpolated median lethal dose of Aerosomes is approximately 2.5 mmol of lipid per kilogram, and the imaging dose is under 5 mumol of lipid per kilogram, yielding a potential therapeutic index of over 500 to 1. Postcontrast US images showed sustained enhancement of all four cardiac chambers as well as enhancement in the aorta, vena cava, and hepatic veins. Aerosomes hold promise as a contrast agent for cardiac and blood-pool imaging. Further work is in progress to characterize and develop this novel US contrast agent. PMID- 1410354 TI - Malignant biliary obstruction: histologic findings after treatment with self expandable stents. AB - Histologic analysis was performed of bile duct tissue from 15 patients who underwent treatment for malignant obstructive jaundice with a self-expandable stent. Stents were in place from 5 days to 21 months. Malignancies included adenocarcinoma of the pancreas or gallbladder or cholangiocellular, hepatocellular, or gastric carcinoma. Stents were blocked by sludge in two cases and tumor overgrowth in two others. Microscopic evaluation showed that stent placement caused complete denudation of the mucosa and mild submucosal inflammation with edema. In all but one patient, the stent was incorporated into the bile duct wall and was covered by a fibrogranulomatous tissue layer after 2 months. In some cases, an epithelium-like cell formation covered the inner surface of the stent. Tumor ingrowth was observed in two patients with poorly differentiated tumors. In stents placed for longer than 2 months, mild to moderate fibrosis and foreign body reaction were observed. Hyperplastic biliary epithelium was not found within the stent or at the stent ends. PMID- 1410355 TI - Pancreatic duct obstruction treated with percutaneous antegrade insertion of a metal stent: report of two cases. AB - Expanding metal stents were used to treat symptomatic pancreatic duct obstruction in two patients with chronic pancreatitis. Both patients initially underwent percutaneous external pancreatic duct drainage and then had metal stents inserted for internal drainage. Both patients remained asymptomatic, and the stents were patent during short-term follow-up periods of 6 and 9 months, respectively. Percutaneous insertion of metal stents, which can be performed to treat pancreatic duct obstruction after a trial of external drainage has been shown to relieve the patient's symptoms, should be considered as an alternative to endoscopic stent placement or surgical drainage. PMID- 1410356 TI - Spiral CT: decreased spatial resolution in vivo due to broadening of section sensitivity profile. AB - Comparable conventional and spiral computed tomographic (CT) scanning protocols for transaxial (n = 30) and multiplanar reformation (MPR) (n = 15) imaging were performed to image the adrenal gland and the upper pole of the right kidney in the same patient, without use of intravenously administered contrast media. The sharpness of soft-tissue-fat interfaces oriented in the transverse (xy) and longitudinal (z) directions was measured as the maximum and full width at half maximum (FWHM) of the edge attenuation profile first derivative. Edge sharpness was qualitatively assessed by three blinded reviewers, who used a four-point scale. In vivo transaxial CT studies showed that the conventional scans produced slightly sharper edges than the spiral scans (mean difference of spiral and conventional FWHM = 0.30 mm [P < .05] [in z direction] and 0.21 mm [P < .05] [in xy direction]). In vivo MPR studies showed that interfaces in the xy plane were significantly less sharp with spiral scanning, whereas interfaces in the z direction were equivalent for conventional and spiral scanning (mean difference of spiral and conventional FWHM = 0.03 mm [P > .05] [in z direction] and 1.19 mm [P < .05] [in xy direction]). Significant respiratory misregistration was present on seven of 15 (47%) conventional MPR scans and on no spiral MPR scans. PMID- 1410357 TI - Increasing contrast when viewing radiographic images. AB - Illuminating a developed photographic film with parallel or nearly parallel light provides increased contrast compared with the contrast obtained with diffuse incident light. The viewer of radiographic images can obtain increased contrast simply by increasing the distance between the view box and the radiograph, since this results in more parallel incident light. The authors found a contrast increase of more than 40% when x-ray film was positioned 4 m from a view box. Tilting the film relative to the surface plane of the view box gave additional contrast increase at the cost of somewhat distorted geometry. The photographic effects involved deserve a more thorough discussion in textbooks of radiologic and radiographic physics. PMID- 1410358 TI - Spleen: dynamic enhancement patterns on gradient-echo MR images enhanced with gadopentetate dimeglumine. AB - To examine the pattern of immediate enhancement with gadopentetate dimeglumine on dynamic magnetic resonance (MR) images of the spleen, this study was divided into two parts: In the first part, the authors retrospectively reviewed the dynamic MR images obtained with a fast low-angle shot (FLASH) sequence in the abdomen immediately after injection of gadopentetate dimeglumine in 137 patients. In the second part, dynamic gadolinium-enhanced FLASH images were prospectively compared with contrast material-enhanced computed tomographic (CT) scans in 17 patients with focal splenic lesions discovered on CT scans. In the first part, 108 patients (79%) had an arciform pattern of contrast enhancement; 22 patients (16%), a uniform pattern of high signal intensity; and seven patients (5%), a uniform pattern of low signal intensity. Most patients had arciform enhancement of the spleen; uniform enhancement occurred in some patients with underlying malignant or inflammatory disease. In the second part, all focal lesions seen on CT scans were seen on dynamic MR images (75 lesions), significantly more than were seen on FLASH images (15 lesions) (P < .001). PMID- 1410359 TI - Gastroesophageal reflux disease: correlation of esophageal pH testing and radiographic findings. AB - In an attempt to ascertain radiologic efficacy in patients with evidence of gastroesophageal reflux disease (GERD) at pH testing, radiographic findings were correlated with pH values obtained with an esophageal monitor worn for a 24-hour period in 112 patients. Fifteen (30%) of 50 patients with abnormal pH test results had esophagitis diagnosed radiographically, compared with six (10%) of 62 with normal pH test results (P < .05). The severity of abnormal pH monitoring results was classified but did not correlate significantly with the prevalence of esophagitis diagnosed radiographically. Hiatal hernia was also more common (80% vs 60%) in patients with abnormal pH test results (40 of 50 patients) than in those with normal results (37 of 62 patients) (P < .05). Pharyngeal, laryngeal, and pulmonary symptoms were common indications for evaluation, and 14 of 27 (52%) patients with hoarseness had an abnormal pH tracing. Only a minority of patients with evidence of GERD as defined by abnormal pH test results had reflux esophagitis diagnosed radiographically. PMID- 1410360 TI - Esophageal motor disorders: videofluoroscopic and manometric evaluation- prospective study in 88 symptomatic patients. AB - Esophageal motor disorders are best evaluated with manometry, which, however, is time-consuming and not generally available. The authors prospectively investigated the yield of videofluoroscopy in detection of esophageal motor disorders in comparison with that of manometry. Eighty-eight patients with dysphagia, globus sensation, noncardiac chest pain, or progressive systemic sclerosis underwent both manometry and videofluoroscopy at 0-32-day intervals. Videofluoroscopy was performed with one swallowing study in the upright position and up to three swallowing studies in the prone oblique position. Manometric diagnoses of achalasia (n = 15), diffuse esophageal spasm (n = 1), nonspecific esophageal motor disorders (n = 44), and adynamic esophagus (n = 9) were made. Videofluoroscopically, 87% of the patients with achalasia, the one patient with diffuse spasms, 73% of the patients with nonspecific esophageal motor disorders, and all of the patients with adynamic esophagus received a correct diagnosis, for an overall sensitivity of 80%. The radiographic specificity was 79%. The authors conclude that videofluoroscopy is a valuable and reasonably sensitive technique for screening for esophageal motor disorders. PMID- 1410361 TI - Intraoperative bile duct sonography during laparoscopic cholecystectomy: experience with a 12.5-MHz catheter-based US probe. AB - During elective laparoscopic cholecystectomy, 20 patients underwent intraoperative evaluation of the biliary tract with a commercial 6.2-F, 12.5-MHz catheter-based ultrasound (US) probe. The study tested the feasibility of this technology for mapping the anatomy of the hepatoduodenal ligament and Calot triangle, assessing bile duct integrity, and detecting choledocholithiasis. The duct was studied with a transmural approach, the catheter being placed parallel to, but remaining outside, the bile duct. The common hepatic duct and common bile duct in the vicinity of the cystic duct were seen in all 20 patients; the junction of the cystic duct with the common hepatic duct was seen in nine patients (45%). After the cystic duct was clamped, no sonographic evidence to suggest bile duct injury was noted in any patient. The transmural imaging approach was tested in four pigs in whose common bile duct a single human calculus had been placed. In all instances the size and location of the calculus were accurately detected. Intraoperative US with a catheter-based system is a safe and effective means for interrogation of the extrahepatic biliary tree during laparoscopic cholecystectomy. PMID- 1410362 TI - Inverted papilloma: evaluation with MR imaging. AB - The authors examined the magnetic resonance (MR) appearance of inverted papillomas to determine if this histologically benign lesion could be distinguished from malignancies of the sinonasal cavity. MR images in 10 patients with histologically proved inverted papilloma were retrospectively reviewed. The signal intensity of inverted papillomas on short repetition time (TR) images was iso- to slightly hypertintense to muscle in all 10 patients. Inverted papillomas had intermediate signal intensity on the long TR/echo time (TE) images. The tumors were iso- or slightly hypointense to fat on long TR/short TE images. In the seven patients who received gadopentetate dimeglumine, all inverted papillomas showed solid inhomogeneous enhancement. A review of eight sinonasal malignancies showed no distinctive signal intensity or enhancement characteristics to help differentiate inverted papillomas from various malignant tumors. The authors conclude that there is no signature MR appearance for the benign inverted papilloma. The main utility of MR imaging is in defining the extent of the lesion. PMID- 1410363 TI - Intraorbital wood foreign body mimicking air at CT. AB - Computed tomography (CT) revealed a 2-cm linear area of extremely low attenuation in the left orbit of a boy who had been poked in the eye with a tree branch. The appearance and attenuation of the area suggested air, so a diagnosis of orbital emphysema was initially considered. Further research indicated that wood mimics the CT attenuation and appearance of air. A wood splinter was surgically removed from the orbit. PMID- 1410364 TI - CT of 338 active professional boxers. AB - Computed tomography (CT) was performed in 338 active professional boxers. CT scans were abnormal in 25 boxers (7%). The most common CT abnormality was brain atrophy (22 cases). Focal lesions of low attenuation consistent with posttraumatic encephalomalacia were noted in only three boxers. Boxers with abnormal CT scans did not differ from those with borderline or normal CT scans in regard to age, win-loss record, number of bouts, or history of an abnormal electroencephalogram. Thirty-seven boxers with borderline CT scans (49%) and 17 with abnormal CT scans (68%) reported a previous technical knockout (TKO) or knockout (KO), compared with only 89 (37%) of the 238 boxers with normal CT scans (P < .01). Brain atrophy was noted more frequently in boxers with a large cavum septum pellucidum (CSP) than in those with a small or no CSP (P < .05). Boxers with abnormal or borderline CT scans who experienced a TKO or KO were slightly older than those with normal CT scans and a history of a TKO or KO (P < .05). PMID- 1410365 TI - Common carotid artery bifurcation: evaluation with spiral CT. Work in progress. AB - To determine the utility of spiral computed tomography (CT) in evaluation of carotid artery stenosis, spiral CT images of 20 patients were compared with images obtained with conventional angiography (20 patients), ultrasound (US) (15 patients), and magnetic resonance (MR) angiography (six patients). The category of stenosis was determined for each internal carotid artery on the basis of the percentage of narrowing: mild = less than 30%, moderate = 30%-69%, and severe = 70%-99%. Occlusions were also noted. The degree of carotid stenosis determined with spiral CT correlated with that determined with conventional angiography in 92% of cases, with that determined with US in 97% of cases, and with that determined with MR angiography in 100% of cases. Calcifications and large ulcers were also well delineated. Spiral CT provided an accurate anatomic depiction of the carotid bifurcation, which could be helpful in preoperative evaluation. The major disadvantage of the technique was the need to postprocess data to remove veins, calcifications, and bone structures from the images. PMID- 1410366 TI - Pituitary adenomas: findings of postoperative MR imaging. AB - Preoperative and postoperative magnetic resonance (MR) images obtained in 25 patients with pituitary macroadenomas (1.1-5.2 cm in diameter) were evaluated to determine normal (physiologic) and abnormal findings after transsphenoidal or subfrontal surgery. With a 1.5-T unit, T1-weighted sagittal and coronal images were obtained before and after administration of gadopentetate dimeglumine. The physiologic changes after surgery included resorption of packing material and sphenoid sinus opacifications, reexpansion of the pituitary gland, and lowering of the optic chiasm. Implanted gelatin foam appeared as an endosellar, circularly enhancing mass that was seen on follow-up studies to have decreased in size. Muscle-and-fat implants appeared as areas of high signal intensity. In 14 patients, residual tumors were found in the suprasellar (n = 4), retrosellar (n = 3), parasellar (n = 8), and/or endosellar (n = 3) space. Residual tumors were differentiated from implant materials by means of location, characteristic signal intensity, and enhancing pattern, which were identical to those of the corresponding preoperative adenoma in 13 cases (93%). Preoperative studies and clinical information are helpful in the evaluation of postoperative MR imaging examinations. PMID- 1410367 TI - Intracranial lesion enhancement with gadolinium: T1-weighted spin-echo versus three-dimensional Fourier transform gradient-echo MR imaging. AB - The conspicuity of lesion enhancement with gadopentetate dimeglumine was evaluated subjectively and quantitatively through calculation of contrast-to noise ratios (C/Ns) on T1-weighted three-dimensional (3D) Fourier transform (FT) gradient-echo (GRE) and two-dimensional (2D) FT spin-echo (SE) images of the brain in 406 consecutive patients. One hundred one enhancing intracranial lesions were present in 61 patients, including intra-(n = 76) and extraaxial (n = 25) processes of neoplastic (n = 68), infectious or inflammatory (n = 13), ischemic (n = 11), or vascular (n = 9) origin. Enhancement was apparent in all lesions on 2DFT SE and 3DFT GRE images, with similar subjective conspicuity in 86.8% (87 of 101) of lesions. Quantitative C/N measurements for 2DFT SE (mean, 17.6) and 3DFT GRE (mean, 17.2) imaging were not significantly different (P = .72). These findings, along with the other advantages of 3DFT GRE imaging, indicate that 3DFT GRE examinations are likely to play a major role in the performance of contrast enhanced MR imaging of the brain. PMID- 1410368 TI - Basal ganglial signal intensity alterations: reversal after discontinuation of parenteral manganese administration. AB - The authors describe magnetic resonance (MR) imaging findings in a patient receiving long-term total parenteral nutrition (TPN) therapy in whom parenteral manganese administration was experimentally discontinued. MR imaging performed while the patient was receiving standard TPN solution demonstrated marked hyperintensity of the globi pallidi on T1-weighted images. Following cessation of parenteral manganese administration for 1 year, repeat MR imaging demonstrated regression of the abnormal signal intensity. PMID- 1410369 TI - Human focal cerebral ischemia: evaluation of brain pH and energy metabolism with P-31 NMR spectroscopy. AB - The authors investigated early human focal ischemia with phosphorus-31 nuclear magnetic resonance spectroscopy at 1.89 T to characterize the temporal evolution and relationship of brain pH and phosphate energy metabolism. Data from 65 symptomatic patients were prospectively studied; none of the patients had had ischemic stroke in the internal carotid artery territory before. Twenty-eight neurologically normal individuals served as control subjects. Serial ischemic brain pH levels indicated a progression from early acidosis to subacute alkalosis. When acidosis was present there was a significant elevation in the relative signal intensity of inorganic phosphate (Pi) and significant reductions in signal intensities of alpha-adenosine triphosphate (ATP) and gamma-ATP compared with those of control subjects. Ischemic brain pH values directly correlated with the relative signal intensity of phosphocreatine (PCr) and the PCr index and inversely correlated with the signal intensity of Pi. There was a general lack of correlation between either ischemic brain pH or phosphate energy metabolism and the initial clinical stroke severity. The data suggest a link between high-energy phosphate metabolism and brain pH, especially during the period of ischemic brain acidosis, and the authors propose that effective acute stroke therapy should be instituted during this period. PMID- 1410370 TI - Isolated choroid plexus cysts in the second-trimester fetus: is amniocentesis really indicated? AB - Choroid plexus (CP) cysts have been associated with trisomy 18, although most fetuses with CP cysts are normal. Since many fetuses with trisomy 18 have other sonographic abnormalities, the necessity of obtaining a karyotype for all fetuses with isolated CP cysts remains controversial. The authors prospectively studied 234 second-trimester fetuses with sonographically discovered CP cysts. Two hundred twenty of them had no other sonographic findings. None of these 220 normal fetuses had evidence of aneuploidy at amniocentesis or an anomaly at birth. Fourteen fetuses had major anomalies detected in utero: 11 had trisomy 18, one had triploidy, and two had normal karyotypes but were structurally abnormal. While size and bilaterality of the CP cysts were not helpful in predicting aneuploidy, the meticulous anatomic survey of fetuses with CP cysts allowed successful identification of all aneuploid fetuses. These data show that the yield of abnormal karyotypes in fetuses with isolated CP cysts is low and may not justify the risk of amniocentesis. PMID- 1410371 TI - Appendicitis: usefulness of US in diagnosis in a pediatric population. AB - One hundred eighty pediatric patients with suspected appendicitis were prospectively examined with graded compression ultrasonography (US) to assess the sensitivity, specificity, and accuracy of graded compression US in the diagnosis of appendicitis in children and to compare those results with results of clinical assessment in the diagnosis of this disorder. Patients were assigned to one of three groups prior to US based on the clinical level of confidence that appendicitis was present and on the planned management decision. Of 141 patients in the low- and intermediate-clinical risk categories, 20 (14%) had appendicitis: US had a sensitivity of 100%, specificity of 97%, and accuracy of 97% in these two groups. Of 39 patients in the high-clinical risk category, 32 (82%) had appendicitis: US had a sensitivity of 81%, specificity of 86%, and accuracy of 82%. Of 52 patients with surgically proved appendicitis, the initial management decision was to discharge to home or admit for observation and further testing in 18 (35%). Results at US were positive for appendicitis in all 18 patients in the latter two categories. PMID- 1410372 TI - Brain abnormalities in male children and adolescents with hemophilia: detection with MR imaging. The Hemophilia Growth and Development Study Group. AB - Cranial magnetic resonance (MR) imaging was performed in 124 male patients (aged 7-19 years), from 14 institutions, in whom a diagnosis of moderate to severe hemophilia was made. Blood tests in all subjects were negative for human immunodeficiency virus. Findings in MR studies were abnormal in 25 (20.2%) subjects. Six lesions in five subjects were classified as congenital. The most commonly identified congenital lesion was a posterior fossa collection of cerebrospinal fluid (five cases). Twenty-two subjects had acquired lesions that were probably related to the hemophilia or its treatment. The most commonly acquired lesions were single- or multifocal areas of high signal intensity within the white matter on T2-weighted images noted in 14 (11.3%) subjects. Two subjects had large focal areas of brain atrophy, and six had some degree of diffuse cerebral cortical atrophy. Three subjects (2.4%) had hemorrhagic lesions. To the authors' knowledge, the unexpected finding of small, focal, nonhemorrhagic white matter lesions has not previously been reported. PMID- 1410373 TI - Blood flow imaging through detection of temporal variations in magnetization. AB - Two hypotheses were tested: (a) that view-to-view variations in bulk phase and modulus of magnetization in vascular volume elements can indicate the presence of disordered blood flow, and (b) that a substantial loss of signal intensity on magnetic resonance (MR) angiograms of poststenotic regions is due to view-to-view changes in magnetization. To test these hypotheses, a technique was developed in which view-to-view variations in transverse magnetization were used to create angiographic projection images, which showed only disordered flow (disordered flow maps) in vitro and in vivo. In phantom studies, this technique recovered signal intensity downstream from stenoses. A combination of disordered flow maps with morphologic images improved visualization of stenotic regions and provided information on characteristics of local flow. These results show that view-to view variations in transverse magnetization occur in regions of disordered flow and are an important cause of loss of signal intensity. This technique can provide information about dynamic blood flow and improve depiction of anatomic structures on MR angiograms. PMID- 1410374 TI - Iliotibial band friction syndrome: MR imaging findings. AB - Six patients with clinical histories and physical examination results consistent with iliotibial band friction syndrome (ITBFS) were examined with magnetic resonance (MR) imaging. Ill-defined decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images was present deep to the iliotibial band, adjacent to the lateral femoral epicondyle. Axial fast imaging with steady-state precession (FISP) gradient-echo sequences were essential in differentiating the ill-defined signal intensity abnormality associated with ITBFS from fluid in the lateral knee joint. None of these patients were found to have lateral meniscal tears, and all responded to conservative measures directed at treating ITBFS. The authors conclude that MR imaging may be useful in confirming or establishing the diagnosis of ITBFS in patients with the appropriate clinical history and distal lateral thigh or lateral knee pain. PMID- 1410375 TI - Ulnar collateral ligament injury in baseball pitchers: MR imaging evaluation. AB - The ulnar collateral ligament (UCL) provides stability to the medial aspect of the elbow during valgus stress. Trauma to this ligament may result from repetitive forceful throwing. Diagnosis of UCL injury has been based on clinical findings of medial joint pain and valgus instability, as direct imaging of this structure has not been available. Eleven baseball pitchers with clinical evidence of UCL injury were evaluated with magnetic resonance (MR) imaging. Surgical correlation was obtained in six patients, four of whom underwent UCL reconstruction. MR imaging findings in UCL injury included laxity, irregularity, poor definition, and increased signal intensity within and adjacent to the UCL. These findings reflect the presence of hemorrhage and/or edema within the UCL due to repeated microtears, which eventually lead to weakening and possible disruption of the UCL. Optimization of spatial resolution, signal-to-noise ratio, and other technical factors is critical for evaluation of the UCL due to its small size. MR imaging is useful in documenting the presence and severity of injury to the UCL and in distinguishing this entity from other causes of elbow pain. PMID- 1410376 TI - Menisci of the knee: radial MR imaging correlated with arthroscopy in 259 patients. AB - Similar to arthrograms, radial plane magnetic resonance (MR) images of the knee provide cross-sectional images of the menisci that are perpendicular to the long axis of the meniscus. The authors evaluated 259 consecutive patients who underwent MR imaging of the knee and arthroscopy. Radial multiplanar gradient recalled-echo imaging was performed--with repetition time of 700 msec, echo times of 12 and 31 msec (700/12, 31), and a flip angle of 20 degrees--as well as sagittal spin-echo imaging (2,500/20, 80). The radial and sagittal images were interpreted separately and then in combination, and findings were compared with arthroscopic reports. There was no statistical difference between the interpretations of the radial and sagittal images in the evaluation of the menisci. When the interpretations of the radial and sagittal images were combined, the sensitivity and specificity improved slightly. The radial images increased the conspicuity of meniscal tears but at the expense of anatomic detail. The sagittal images enabled better evaluation of the meniscocapsular attachment region and some flap tears of the meniscal free edge. The interpretive accuracies of the combination of sagittal and radial images were 92% and 93% for the medial and lateral menisci, respectively. PMID- 1410377 TI - Diagnosis of soft-tissue masses with MR imaging: can benign masses be differentiated from malignant ones? AB - A blinded, retrospective review of 83 soft-tissue masses (49 benign and 34 malignant) was performed to evaluate the ability to distinguish benign from malignant soft-tissue masses with magnetic resonance (MR) imaging. The correct histologic diagnosis was reached in 31% of cases by one reader and in 16% of cases by the second reader. Mean sensitivity was 50% for benign masses and 80% for malignant masses. The majority of both benign and malignant masses had inhomogeneous signal intensity and at least partially irregular borders. Malignant masses uncommonly had smooth borders and homogeneous signal intensity. MR imaging can be used to evaluate the extent of soft-tissue masses, but most masses will require biopsy to determine if they are benign or malignant. PMID- 1410378 TI - Osteosarcoma after chemotherapy: evaluation with contrast material-enhanced subtraction MR imaging. AB - A new magnetic resonance (MR) technique, gadolinium-enhanced subtraction MR imaging, was developed to evaluate the response of patients with osteosarcoma to chemotherapy. Ten patients, who had received chemotherapy for osteosarcoma of the lower extremity, underwent MR imaging 3 days before surgery. After routine MR imaging was performed, subtraction MR was performed in the plane in which the tumor was best visualized. With gadopentetate dimeglumine (0.1 mmol per kilogram) on a standard MR console, subtraction images were created by subtracting precontrast images from gadolinium-enhanced T1-weighted images. The time of maximal tumoral vascular uptake was 1 1/2 minutes after injection, and, therefore, the subtracted image obtained at this time was used for evaluation of viable tumor. Independently, radiologists and histopathologists examined their respective studies for viable tumor to differentiate responders from nonresponders. Four of 10 osteosarcomas were classified as good responders because they appeared as nonenhancing masses, with or without enhancing thin lines, or small nodules (< or = 3 mm wide). At histopathologic examination, all were good responders with less than 3% viable tumor. Six of 10 osteosarcomas were classified as nonresponders because they appeared as enhancing high-signal intensity masses measuring more than 3 mm in width. Five tumors had between 18% and 43% viable tumor cells. PMID- 1410379 TI - Assessment of whole-body composition with dual-energy x-ray absorptiometry. AB - Dual-energy x-ray absorptiometry (DXA) allows noninvasive direct measurement of the three major components of body composition: lean body mass (LBM), fat body mass (FBM), and bone mineral body mass (BBM). To study the accuracy and short term and long-term precision of body composition measurements, the authors measured body composition with DXA in 60 healthy young adults. Independent measurement of LBM (LBMK-40), obtained from the determination of the whole-body content of potassium-40 with a whole-body scintillation detector, was highly correlated with LBM determined with DXA (LBMDXA) (LBMK-40 = 1.069.LBMDXA,R2 = .996). Assessment of body composition in 10 patients with acquired immunodeficiency syndrome (AIDS) and 10 patients with cystic fibrosis was performed with DXA. The AIDS patients showed a marked decrease in LBM, while in patients with cystic fibrosis, LBM and BBM were decreased. DXA measurements of body composition appeared accurate and precise enough to be of clinical relevance in detecting specific alterations of body composition. PMID- 1410380 TI - Subperiosteal resorption: effect of full-frame image compression of hand radiographs on diagnostic accuracy. AB - Image compression is essential to handle a large volume of digital images, including computed tomographic, magnetic resonance, computed radiographic, and digitized images in a digital radiology operation. Developed during the past few years, full-frame bit allocation performed with the cosine transform technique has been proved to be an excellent irreversible image compression method. This article describes the effect, on the accuracy of diagnosis of subperiosteal resorption, of using the hardware compression module to produce hand radiographs. Receiver operating characteristic analysis of the interpretation of 71 radiographs by five observers demonstrated that there is no statistically significant difference in diagnostic accuracy between the original radiographs and compressed and reconstructed images obtained with a compression ratio as high as 20:1. PMID- 1410381 TI - Expandable intravascular catheter: percutaneous use for endoluminal retrievals. AB - Percutaneous use of an expandable vascular access catheter that can be deployed to temporarily occlude the entry vessel during retrieval of embolic material is described. The catheter was used to facilitate removal of two intraarterial objects, a postangioplasty free atheroma fragment and a displaced Gianturco coil. The expanded catheter end was equal to the arterial lumen, thus preventing distal embolization. The large distal lumen also facilitated plaque or foreign body removal by allowing deployment of various endovascular tools. PMID- 1410382 TI - CT angiography with spiral CT and maximum intensity projection. AB - The authors describe a technique for obtaining angiographic images by means of spiral computed tomography (CT), preprocessing of reconstructed three-dimensional sections to suppress bone, and maximum intensity projection. The technique has some limitations, but preliminary results in 48 patients have shown excellent anatomic correlation with conventional angiography in studies of the abdomen, the circle of Willis in the brain, and the extracranial carotid arteries. With continued development and evaluation, CT angiography may prove useful as a screening tool or replacement for conventional angiography in some patients. PMID- 1410383 TI - The left atrial catheter: its uses and complications. AB - The authors describe the radiographic appearance of the left atrial catheter, a widely used postsurgical intracardiac device. Recognition of the characteristic appearance of this catheter should be of value in detection of potential complications, including line fracture with resultant retention and/or embolization, infection, prosthetic valve dysfunction, and even cardiac tamponade. PMID- 1410384 TI - Gyriform enhancement in tuberous sclerosis simulating infarction. PMID- 1410385 TI - Pulmonary embolism during compression US of the lower extremity. PMID- 1410386 TI - Verification of lumbar vertebral bodies. PMID- 1410387 TI - Radiological Society of North America 78th scientific assembly and annual meeting. November 29-December 4, 1992. Program and Abstracts. PMID- 1410388 TI - Nurse suspended for failure to attend AIDS patient. PMID- 1410389 TI - When patients refuse to cooperate--nurses may be responsible! Case in point: Hackathom v. Lester E. Cox Medical Center (624 S.W.2d 472--MO (1991)). PMID- 1410390 TI - Legal case briefs for nurses. VA: home health nurse injured in auto accident: workers' comp. issue; OH.: nurse detained for shoplifting: hosp. sued for false imprisonment. PMID- 1410391 TI - Nursing assistant rapes patient: hospital vicariously liable. Case in point: Samuels v. Southern Baptist Hospital (594 So 2d. 571--LA (1992)). PMID- 1410392 TI - Can handicapped nurses "write their own ticket"? PMID- 1410393 TI - Who has responsibility to monitor O.R. blood loss? Case in point: Uhr v. Lutheran General Hospital (589 N.E.2d 723--IL [1992]). PMID- 1410394 TI - Legal case briefs for nurses. CO: failing student sues college: court refuses to intervene; KY: nurse denies "recent accident": worker's comp. issue. PMID- 1410395 TI - Failure to determine breech position: M.D. or R.N. duty? Case in point: Alvis v. Henderson Obstetrics, S.C. (592 N.E.2d 678--[1992]). PMID- 1410396 TI - The development of ion regulation at the blood-brain barrier. PMID- 1410397 TI - Goldfish ependymins: cerebrospinal fluid proteins of meningeal origin. AB - Ependymins are unique secretory proteins from the goldfish brain which have calcium binding capacity. They are synthesized in the leptomeninx and appear subsequently as the predominant protein constituents in the cerebrospinal fluid (CSF). In contrast, the serum is nearly devoid of ependymins. The perimeningeal fluid (PMF) between the meninx and the skull represents a mixture of CSF and serum. The different composition of PMF and CSF implies that there is no open communication between these two compartments. Separation is probably achieved by an arachnoid-like meningeal barrier as proposed from ultrastructural studies. This basic CSF system of fish is compared with that of higher vertebrates. PMID- 1410398 TI - An approach to study of transport of trace metals at the blood-brain barrier. PMID- 1410400 TI - Peptide receptors of the blood-brain barrier and substrate transport into the brain. AB - The BBB is a target for some peptide signals, as demonstrated by our group for arginine-vasopressin (AVP) and atriopeptin (ANP). Peptide molecules contacting the luminal surface of endothelial cells interact with specific high-affinity binding sites. The minimal simple diffusion of peptide molecules across the layer of endothelial cells which are connected by tight junctions is most probably without any significance under physiological conditions, although that question should be checked for brain regions like the olfactory bulb in which some leakiness of the BBB can be demonstrated. The AVP- and ANP-receptors at least partly localized at the luminal surface of the endothelial cells are heterogeneously distributed in the vessels of the brain. The number of AVP receptors is up-regulated by ligand deficiency, which induces furthermore a decrease in the receptor affinity. At physiological concentrations AVP and ANP do not affect the tightness of the BBB, but regulate the transcellular transfer of essential substances from blood to brain. AVP decreases the Km and Vmax of the transporter of large neutral amino acids, and ANP alters the water permeability of the endothelial cell layer. The phenomenon that the cells of the tight epithelium representing the BBB need information from blood-borne peptide signals for the regulation of intercompartmental transport processes seems to be only a special case of a general principle concerning tight epithelial cell layers which separate compartments containing fluids of different composition; amino acid transport across the intestine is regulated by specific peptides contacting that barrier, the casomorphins. PMID- 1410399 TI - Localization patterns for immunoglobulins and albumins in the brain suggest diverse mechanisms for their transport across the blood-brain barrier (BBB). PMID- 1410402 TI - Experimental models of altering the blood-brain barrier. AB - The passage of a substance from blood to brain can be enhanced by altering the permeability of the substance itself or by altering the BBB characteristics. Example of the former is to increase lipid solubility, glycosylation and cationization, liposome entrapment and coupling to carriers. Unselective opening of the BBB can be obtained by a local or systemic increase of the intravascular pressure, by intracarotid injection of hyperosmolar solutions or by substances that alter the endothelial surface charge such as protamine sulphate. Substances that alter the fluidity of membranes can reduce or enhance the permeability of the BBB. In experimental models involving temporary opening of the BBB possible long-term hazardous effects must be considered. PMID- 1410401 TI - The interaction of some centrally active drugs with the blood-brain barrier and circumventricular organs. PMID- 1410403 TI - Age-related pathophysiology of the blood-brain barrier in heat stress. AB - The possibility that the blood-brain barrier (BBB) might play an important role in the pathophysiology of heat stress (HS) has been examined in young (age 8-9 weeks) and adult (age 24-32 weeks) rats. Exposure of young rats to 4 h HS at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 47 50%, wind velocity 20-26 cm/sec, simulating the environmental conditions of Varanasi, India, during the month of June) resulted in a marked hyperthermia (41.7 +/- 0.23 degrees C) and behavioral symptoms. In these animals there was a profound increase in the permeability of the BBB to Evans blue-albumin (EBA) (464%) and to 131I-sodium iodide (515%), accompanied by a marked increase in the brain water content (4%), of the levels of serotonin (5-hydroxytryptamine, 5-HT) in plasma (687%) and in brain (267%) and a pronounced reduction (30%) in cerebral blood flow (CBF). Morphological examination using light- and electron-microscopy revealed profound neuronal changes associated with a marked increase in glial fibrillary acidic protein (GFAP) and in vimentin immunoreactivities, together with a substantial reduction in myelin basic protein (MBP) immunostaining in the brain. These changes were more pronounced in the brain-stem reticular formation, pons and medulla region. On the other hand, exposure of adult animals to the same intensity of HS resulted in mild or no changes in BBB permeability, content of brain water and 5-HT in the plasma and brain, CBF or other cellular changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410404 TI - Effect of central administration of angiotensin II on cerebrospinal fluid formation in rabbits. AB - The effect of central administration of AII on CSF formation was studied in alpha chloralose and urethane anesthetized rabbits using the ventriculocisternal perfusion method. AII infused i.c.v. at rates of 5.5 and 55 pg/min significantly decreased CSF production by 25% and 35%, respectively. In contrast, AII when given at 5.5 ng/min did not change CSF formation. It seems that drop in CSF production observed during central administration of AII at low doses is mediated by both increased vasopressin release and activation of the sympathetic nervous system. The lack of changes in CSF formation with the highest AII dose used is not clear at present and awaits further investigation. Specific AII antagonist, saralasin, was found to significantly increase CSF production in four of five animals studied. It is suggested that in normal conditions AII may exert a tonic inhibitory effect on CSF formation. PMID- 1410405 TI - Tracer uptake by circumventricular organs--a relative measure of blood supply to the brain. PMID- 1410406 TI - Density of perfused capillaries in living human brain during functional activation. AB - Recent evidence has indicated that functional activation of cerebral cortex is accompanied by increases of blood flow and glucose consumption but not oxygen consumption. No explanation has been advanced for this change of the flow metabolism couple. We formulated the hypothesis that oxygen delivery to brain tissue is diffusion-limited by the enormous hemoglobin binding, and rate-limiting for the oxygen consumption of the tissue. One prediction of this hypothesis is very low oxygen tensions in the tissue. A second prediction is the inability of oxygen consumption to increase during functional activation in the absence of recruitment of capillaries for the oxygen diffusion capacity. We designed a study to test the latter prediction by calculating the density of functioning capillaries during vibrotactile stimulation of the parietal cortex. We defined functioning capillaries as capillaries that transport glucose and therefore calculated the capillary density from the glucose diffusion capacity (K1) of the cerebral capillaries. We confirmed the presence of a partial flow-CMRglc couple (2:1) during the functional activation. Oxygen consumption did not change despite an increase of capillary density in proportion to the change of blood flow. PMID- 1410407 TI - Circumventricular organ capillaries. AB - Most circumventricular organs (CVOs) have unusually dense and permeable capillary networks that facilitate secretion of or tissue penetration by circulating substances, unlike other nervous system structures wherein blood-brain barrier (BBB) properties of the capillary endothelium limit solute permeability. In this brief review, I shall discuss new facts from recent experiments, and draw on interpretations from previous studies, to illustrate how capillary systems vary both between and within some CVOs, how closely microvascular properties coincide topographically with the distribution and density of neuropil, transmitter substances and hormonal binding sites, and how physiological data can be combined with morphological descriptions of capillary beds to accent specialized processes of blood-brain solute exchange in individual CVOs. The emphasis of this paper is on exchange microvessels of the rat area postrema (AP), subfornical organ (SFO) and median eminence (ME) which are regions of dense binding for several hormones and contain appreciable numbers of neurons (AP and SFO) or neural terminations that may be part of the sensing apparatus for humoral messengers of homeostatic systems. The work is intended to highlight established concepts about the process of blood monitoring by CVOs, summarize new morphological and physiological characteristics of their capillaries, and provide clues to novel research that could foster further understanding of these curious sentinel and secretory organs of the brain. PMID- 1410408 TI - Adrenalectomy aggravates ischemic brain edema in female Sprague-Dawley rats with carotid arteries ligated. AB - The effect of adrenalectomy has been investigated in a model of global cerebral ischemia. After bilateral carotid ligation the mortality rate was increased in adrenalectomized rats, and this effect was prevented by glucocorticoid pre treatment. Adrenalectomy accelerated the appearance of the symptoms of cerebral ischemia, resulting in a moderate aggravation of brain edema and in a significant decrease in the concentration of high-energy phosphate esters. Our findings support the view that endogenous glucocorticoids may play a role in the amelioration of ischemic brain injuries in rats. PMID- 1410409 TI - Atrial natriuretic factor in the subfornical organ and the organum vasculosum laminae terminalis. PMID- 1410410 TI - Steroid hormones and circumventricular organs. PMID- 1410411 TI - Receptor and effector mechanisms in the pineal organ. PMID- 1410412 TI - Central release of vasopressin: stimuli, dynamics, consequences. PMID- 1410413 TI - Cytochemistry of CSF-contacting neurons and pinealocytes. AB - Gamma aminobutyric acid (GABA)-immunoreactive neurons of the paraventricular organ of the bony fish Coregonus albus send dendrites into the third ventricle. Their axons run to the synaptic zone of the infundibular lobe. The dendrites may take up some chemical information from the third ventricle, while the axons communicate it to the neuropil of the hypothalamus perhaps to modify its activity according to the state of the CSF. Serotonin-immunoreactive CSF-contacting neurons in the spinal cord of the hagfish Myxine glutinosa from dendrite terminals in the central canal and bear stereocilia like known mechanoreceptors. The Reissner's fiber runs above the stereocilia and flows out from the central canal through its caudal opening. Possibly, the fiber keeps open this aperture and ensures the flow of the CSF, which may serve as a mechanoreceptory input for the CSF-contacting neurons. In the pineal recess of hedgehog, CSF-contacting pinealocytes develop enlarged cilia corresponding to the photoreceptor outer segments of submammalian pinealocytes. Potassium pyroantimonate cytochemistry shows a similar localization of calcium ions in the mammalian pinealocyte as in the submammalian photoreceptor ones. Pineal calcifications are present in some birds (goose, duck) and may be connected to the photoreceptory Ca-exchange of the pineal organ. Axonic processes of pinealocytes form synapses on secondary neurons in mammals (hedgehog, rat, cat). Such neurons are also present in human pineals. Axons of these neurons constitute a pinealofugal pathway. In the cat, some of the intrinsic pineal neurons are GABA-immunoreactive, they form axodendritic and axo axonic synapses (inhibitory?) on immunonegative neurons and pinealocytes, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410414 TI - A role for centrally-released vasopressin in brain ion and volume regulation: a hypothesis. PMID- 1410415 TI - Comparative ultrastructure and opsin immunocytochemistry of the retina and pineal organ in fish. AB - The pineal organ and retina were compared in developing charr and cisco, further in adult cisco, eel, creek chub, dace, zebrafish and black moli by opsin immunocytochemistry. In prehatching charr embryos, retinal rods and cones and pinealocytes displayed well-developed outer segments and formed synapses. Differentiation of the retina started centrally but was more advanced in the dorso-caudal retina than rostroventrally. The pineal organ differentiated earlier distally than proximally. In the cisco, the pineal organ and retina differentiated around hatching. In charr embryos, further in the larval and adult species studied, opsin immunoreactivity was found in retinal rods, accessory cones and many "rod-like" pinealocytes, a result indicating the presence of rhodopsin and/or porphyropsin. Retinal principle cones, long and short cones and some "cone-like" pinealocytes were opsin-immunonegative; they are thought to represent red- and/or u.v./violet-sensitive elements. The pineal organ may be involved in negative phototaxic behavior. Both the retina and pineal organ appear to be suitably differentiated to detect light in the larval and embryonic charr. PMID- 1410416 TI - Circadian rhythm and pharmacologic regulation of the monodeiodination of 3,3',5,5'-tetraiodothyronine in the pineal gland. PMID- 1410417 TI - Response of CFU-GM (colony forming units for granulocytes and macrophages) from intact and pinealectomized rat bone marrow to murine recombinant interleukin-3 (rIl-3), recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF) and human recombinant erythropoietin (rEPO). AB - The present study provides evidence, for the first time, of a role of the pineal gland in the proliferation of CFU-GM under the influence of different cytokines. The degree of colony formation in different cytokine groups was evaluated after 24 h, 3, 7 and 10 days. The colony growth in the present type of bone marrow cell cultures slows after the 10th day and ceases after the 14th day of incubation. The results show that rGM-CSF and the combination of rGM-CSF with rIl-3 and with rEPO stimulate the colony formation of granulocytes and macrophages. A 50% general reduction in the colony number was noted in the pinealectomy group. Their pattern of response to the different cytokines was similar to that of the intact group. It is suggested that the pineal activity has a physiological role in important aspects of host defence mechanisms, such as the proliferation of CFU GM. PMID- 1410418 TI - Immunocytochemical demonstration of serotonin-immunoreactive cerebrospinal fluid contacting neurons in the paraventricular organ of pigeons and domestic chickens. AB - The paraventricular organs (PVO) of the pigeon and domestic chicken contain at least three types of serotonin-immunoreactive (serotonin-ir) CSF-contacting neurons. Type 1 neurons were predominant. They had two bipolar extending processes. The somata were mostly found in the pars hypendymalis. Type 2 neurons were characterized by thin and long apical processes. Their perikarya were found in the pars distalis of the PVO or the more lateral area of this organ. Type 3 neurons were considerably smaller and had round somata. They were mostly bipolar with thin and short dendritic processes and thin basal processes. A small number of this type was conspicuous along the cranial peripheral region of the PVO. In addition to the PVO area, aggregations of small, bipolar serotonin-ir CSF contacting neurons were shown in the most caudal wall of the third ventricle of both species, distributed medially or paramedially. Immunoelectron microscopy revealed many dense granules in apical ventricular processes and perikarya. Synaptic connections were frequently observed on basal processes. PMID- 1410419 TI - The bovine subcommissural organ: cytochemical and immunochemical characterization of the secretory process. AB - Specific glycoproteins of the bovine subcommissural organ (SCO) were studied by means of various techniques: light and electron microscopy, immunoaffinity chromatography, electrophoresis and Western blotting. Use of lectins (Con A, WGA, PHA-E and -L, LCA) allowed to specify the synthesis and release of complex-type glycoproteins that bear high-mannose-carbohydrate chains in their precursor forms and probably triantennary carbohydrate chains in their mature forms. Antibodies raised against SCO extracts were characterized by means of various tests and used to purify specific compounds. Immunopurified fractions using A99 polyclonal antibody contained numerous polypeptides reactive with Con A, their apparent molecular weight (MW) ranging from 240 to 50 kDa. Only two glycopeptides were strongly labeled with WGA (98 and 52/54 kDa MW). Immunopurified fractions using C1B8A8 monoclonal antibody, specific of the complex-type glycoproteins at different steps of glycosylation, showed three specific Con A-reactive polypeptides at 88, 54 and 34 kDa MW. Only the 34 kDa glycopeptide was strongly labeled with WGA. The latter could correspond to the monomeric form of the secreted compound. Electrophoretical analyses of Reissner's fiber material allowed the detection of a WGA-positive smear in the upper part of the blots, suggesting that the complex-type glycoproteins, when released into the CSF, constitute a stable polymer. PMID- 1410420 TI - Developmental neuron-glia interactions: role of serotonin innervation upon the differentiation of the ependymocytes of the rat subcommissural organ. AB - The rat subcommissural organ (SCO), which forms the roof of the third ventricle is an adequate model to study certain mechanisms of neuron-glia interactions in vivo. The ependymocytes, the main component of the SCO, have a glial origin. They possess particular phenotypic characteristics: they accumulate [3H]GABA by a specific uptake mechanism, contain transitory GFAP during ontogenesis and do not express PS100; on the other hand they receive a 5HT input which forms typical synaptic contacts. This innervation is of particular interest to approach neuron glia interactions during the differentiation. Studies of GABA uptake carriers during ontogenesis in SCO ependymocytes show a correlation between the onset of the 5HT innervation and the advent of the GABA uptake. Moreover, destruction of the 5HT innervation by a neurotoxin (5-7-dihydroxytryptamine), before its arrival at the SCO in newborn rat, inhibits the formation of the GABA uptake system and causes the expression of PS100 in adult SCO cells. On the other hand, the SCO of newborn rats transplanted to the fourth ventricle of an adult host rat had no capacity to take up GABA and expressed PS100 3 months after its transplantation. Finally, the SCO ependymocytes of species devoid of 5HT innervation (rabbit, mice) were unable to take up GABA and contain PS100. These data suggest that neuron-glia interactions are necessary for the advent of GABA uptake carriers and can control the expression of glial markers during ontogenesis in SCO ependymocytes. PMID- 1410421 TI - Development of the median eminence during ontogenesis (morpho-functional aspects). PMID- 1410422 TI - Neuro-hemal and neuro-glial specificities in the neural lobe of the pituitary gland. PMID- 1410423 TI - Drug metabolizing enzymes in the rat pituitary gland. AB - Brain protection against chemicals is mainly provided by the specific properties of cerebral microvessels forming the blood-brain barrier. In addition, several drug metabolizing enzymes have been evidenced both in brain tissue and in cerebral capillaries, suggesting their participation in the enzymatic protection of this organ. The pituitary gland, like true circumventricular organs, lacks a tight vascular endothelium and therefore is especially sensitive to blood-native toxic or pharmacologically active molecules. We report here the presence of cytochrome P-450 in the pituitary gland and its main mitochondrial localization. The O-dealkylase activity measured towards 7-benzoxyresorufin, a substrate for the main cytochrome P-450 isoforms involved in the metabolism of xenobiotics, was 5 times higher in the pituitary gland than in the brain cortex. Similarly, microsomal epoxide hydrolase, which inactivates reactive epoxides to trans diol molecules, and two conjugating enzymes, 1-naphthol UDP-glucuronosyltransferase and glutathione-S-transferase, display respectively 6, 4 and 7 times higher activities in the pituitary gland. 7-Benzoxyresorufin-O-dealkylase, 1-naphthol UDP-glucuronosyltransferase and membrane-bound epoxide hydrolase activities were significantly increased in the pituitary gland as an adaptive response to an in vivo treatment by an exogenous inducer, 3-methylcholanthrene. These results suggest that these enzymatic systems play a role in the protection of the pituitary gland towards drugs or toxic substances. PMID- 1410424 TI - Integrative mechanisms and the maintenance of cardiovascular and body fluid homeostasis: the central processing of sensory input derived from the circumventricular organs of the lamina terminalis. PMID- 1410425 TI - Efferent neural pathways of the lamina terminalis subserving osmoregulation. AB - Studies in rats and sheep show that neurons in the CVOs of the lamina terminalis provide extensive neural input to the vasopressin-containing cells of the supraoptic nucleus. This input is both by direct pathways and via a synapse in the MnPO which also has projections to the vasopressin-containing cells of the SON. Neurons throughout the lamina terminalis (including possible osmoreceptors in the OVLT and subfornical organ) are activated by systematic hypertonicity. It is likely that in response to hypertonicity they signal the SON and PVN to release vasopressin and elsewhere to elicit other osmoregulatory responses such as thirst and the excretion of sodium. PMID- 1410426 TI - The role of OVLT in fever and antipyresis. PMID- 1410427 TI - Pregnancy and opioid interactions with the anterior perithird ventricular input to magnocellular oxytocin neurones. PMID- 1410428 TI - Neurophysiological analysis of mechanisms for subfornical organ and area postrema involvement in autonomic control. PMID- 1410430 TI - Progressive increases of protein synthesis in the circumventricular organs during chronic dehydration in rats. AB - The quantitative autoradiographic method with L-(35S)methionine was applied to investigate the effect of chronic dehydration on rates of protein synthesis in circumventricular organs (CVOs). Water deprivation for 1, 2 and 3 days causes progressive increases of protein synthesis in the subfornical organ (SFO), the area postrema, the organum vasculosum laminae terminalis and the neurohypophysis. Chronic salt ingestion with 2% NaCl in drinking water for 3 days resulted in increases of protein synthesis in the CVOs similar to those found after 3 days water deprivation, with only one exception, the SFO, in which the rise in protein synthesis was of lower amplitude after 3 days salt ingestion as compared to 3 days water deprivation. These results suggest that several circulating factors related to intracellular dehydration and the high plasma levels of the neurohormones vasopressin and oxytocin are probably important determinants of the rise of protein synthesis in circumventricular organs. Alternatively, the elevated level of blood-borne angiotensin II may well explain the higher metabolic response of the SFO following water deprivation compared to salt ingestion. PMID- 1410429 TI - Functional hypothalamic angiotensin II and catecholamine receptor systems inside and outside the blood-brain barrier. AB - To elucidate the contribution of various hormones and neuromodulators in the central nervous control of body fluid homeostasis, the saltwater-acclimated Pekin duck represents an ideal model due to the cytoarchitecture of its hypothalamus, and the marked systemic and hypothalamic sensitivity of its osmoregulatory system. Employing animal physiology, electrophysiology, histochemistry and receptor binding techniques, the role of angiotensin II (A II) and norepinephrine (NE) as both circulating hormones and neurotransmitters in central osmoregulation through interaction with neuronal targets inside and outside the blood-brain barrier (BBB) could be investigated. Application of both agents into the systemic circulation or into the cerebrospinal fluid of conscious animals, and the monitoring of hypothalamo-neurohypophyseal antidiuretic hormone ADH (= AVT) release, cardiovascular parameters such as mean arterial pressure (MAP) and avian salt gland function allowed to discriminate between actions of A II and NE at sites within or outside the BBB. Of the latter, the median eminence (ME), the subfornical organ (SFO) or the organum vasculosum laminae terminalis (OVLT) are of prime importance. Receptor autoradiography using radioiodinated ligands specific for A II, alpha 1-, alpha 2- and beta-receptors including the pharmacological characterization of these binding sites permit to establish a molecular correlate of the modulatory actions of both A II and NE. PMID- 1410431 TI - Effect of arginine vasopressin on blood vessels of the perfused choroid plexus of the sheep. AB - The perfused sheep choroid plexus was used to evaluate the response of the plexus blood vessels to systemically administered arginine vasopressin (AVP). AVP was found to decrease the diameter of the choroid plexus arterioles with a maximum change of 28 +/- 5% (mean +/- S.E.) at a plasma peptide concentration of 10(-7) M. This effect was blocked by the specific V1-vasopressinergic antagonist, d(CH2)5Tyr(Me)AVP. In contrast, venules were found not to show any appreciable response to AVP. Plasma AVP concentrations necessary to evoke a significant response of the choroid plexus arterioles are much higher than the highest plasma peptide levels observed in different physiological or pathophysiological situations. Some indirect evidence suggests, however, that AVP might be released within the choroid plexus from the vasopressinergic synaptic terminals, thus reaching a considerably high local concentration. It is possible then that the plexus vessels' tone could be controlled by the putative vasopressinergic neuronal fibers ending in the choroid plexus. PMID- 1410432 TI - The human hypothalamus in development, sexual differentiation, aging and Alzheimer's disease. PMID- 1410433 TI - Endogenous opioids regulate intracerebral oxytocin release during parturition in a region-specific manner. PMID- 1410435 TI - ANF-induced modulation of ADH-release in the rabbit and Pekin duck. AB - The atrial natriuretic factor (ANF) as an osmoregulatory hormone causes a reduction of extracellular fluid volume primarily through stimulation of renal and extrarenal water and sodium elimination. Consequently, ANF counteracts the renin-angio-tensin II-aldosterone (RAAS) and the antidiuretic hormone (ADH) systems at their target organ level. The possible direct interaction of ANF with the hypothalamo-neurohypophyseal ADH system was investigated in conscious ducks and rabbits during conditions of eu- and dehydration. In euhydrated animals, the plasma concentration of ADH remained unchanged during the systemic infusion of species-specific ANF, whereas in dehydrated rabbits but not ducks, the plasma concentration of ADH was significantly decreased. These differences in ADH modulation were supported by the localization of binding sites for radiolabeled ANF at the sites of ADH release, the median eminence (ME) and neurohypophysis (NH) of the rabbit but not duck brain, using receptor-autoradiography. For both species, circumventricular organs lacking a functional blood-brain barrier (BBB) such as the subfornical organ (SFO), the organum vasculosum of the laminae terminalis (OVLT), the pineal and the choroid plexus (ChP), as well as the ependymal lining of the third ventricle (VIII) were labeled specifically. Within the BBB, binding sites for ANF could not be detected in the ADH-synthesizing paraventricular (PVN) and supraoptic nuclei (SON) of either species, however, sites were observed in the anterior median nucleus of the hypothalamus (AM) of the duck brain. In the AM as well as the PVN and ME, the existence of a brain intrinsic ANF system could be demonstrated for the Pekin duck using immunocytochemistry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410434 TI - Evidence against participation of V2 receptors in the increase of cerebral blood flow during hypoxemia in the rat. AB - Cerebral blood flow (CBF) and cerebral utilization of oxygen (CMRO2) were studied in anesthetized and artificially ventilated rats during normoxemia and hypoxemia before and during intravenous infusion of a selective blocker of V2 vasopressinergic receptors (d(CH2)5 [D-Ile2,Abu4] AVP, 15 micrograms/kg per hour i.v.). CBF was measured by means of the intracarotid 133-Xe injection method. CMRO2 was calculated from the oxygen arteriovenous difference using the Fick principle. Infusion of V2 antagonist did not influence CBF, CMRO2 or blood pressure (BP) during normoxia. It also did not change the response of cerebral circulation to hypoxemia. Increase in CBF and decrease in cerebrovascular resistance (CVR) during hypoxemia were similar during the infusion of V2 blocker or without it. However, the decrease in BP observed during hypoxemia in the control group of rats was prevented in the group of animals which were infused with V2 blocker. PMID- 1410436 TI - Vasopressin involvement in central control of blood pressure. PMID- 1410437 TI - Neuronal plasticity depending on a glycoprotein synthesized in goldfish leptomeninx. AB - Transcription of a calcium and zinc binding, nervous system-specific cell adhesion glycoprotein, ependymin, in goldfish leptomeninx was significantly enhanced after active avoidance conditioning, followed by enhanced translation and secretion. Inactivation of secreted ependymin by injected antisera interfered with behavioral adaptations. In addition to the site of synthesis in reticular cells of the leptomeninx electronmicroscopic immunochemistry localized the protein to tectal neurons of the superficial plexiform and the periventricular cell layers. Detection of ependymin in cells where it is not synthesized, namely in neurons, suggests a re-uptake during functional activity of the CNS and assigns a pivotal role to the cerebrospinal and interstitial brain fluids for the distribution of protein factors that support axonal growth and neuronal plasticity. PMID- 1410438 TI - Neuropeptides within the nucleus tractus solitarii modulate the central cardiovascular control process. AB - Local administration of small amounts of vasopressin, angiotensin or endothelin into the nucleus tractus solitarii elicits similar decreases in blood pressure and heart rate. These central effects oppose the peripheral action of these hormones on the cardiovascular system. The baroreceptor-heart-reflex, however, is influenced differentially: vasopressin and angiotensin II enhances the sensitivity of the reflex but angiotensin III impairs it. In this way the cardiovascular system may be adjusted to different demands including those related to electrolyte and fluid homeostasis. PMID- 1410440 TI - Chromatographically identified oxytocin in the human peripheral nervous system. AB - Immunoreactive oxytocin (OXT) detected in extracts of human coeliac ganglia and nn. vagi was characterized by high-performance liquid chromatography (HPLC). HPLC/RIA examinations demonstrated that a major part of the immunoreactive material in both investigated areas co-eluted with a reference synthetic OXT, but in the extracts of coeliac ganglia a second immunoreactive peak was also observed. PMID- 1410439 TI - Disturbances of volume regulation in chronic alcoholics: a correlation with the excitability of the central nervous system. PMID- 1410442 TI - The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs. PMID- 1410441 TI - Intracerebral grafting of solid tissues and cell suspensions: the blood-brain barrier and host immune response. PMID- 1410443 TI - The neuronal substrate of integration in the oculomotor system. PMID- 1410444 TI - Two prokaryotic transcriptional enhancer systems. PMID- 1410445 TI - Latent viruses and mutated oncogenes: no evidence for pathogenicity. PMID- 1410446 TI - Structure, function, evolution of transcription factor IIIA. PMID- 1410447 TI - Developmental regulation of nuclear gene expression in Trypanosoma brucei. PMID- 1410448 TI - The role of protein domains in the assembly process of intermediate filaments. PMID- 1410449 TI - Modeling DNA structures. AB - For a molecule of biological importance, one expects a strong correlation between the three-dimensional structure and its biological function(s). Molecular simulations allow the prediction of physical properties of macromolecules. Many of these properties are closely related to the molecular structure. Model building studies may thus supplement structurally low-resolution experimental data with detailed three-dimensional hypothetical atomic models. Such studies may give a consistent integral view of a wealth of experimental data. In most cases, such models will predict the outcome of certain experiments. Their actual results will often either confirm the model, be used for further refinement, or demand a major revision. Empirical force-fields provide a large amount of physicochemical knowledge concerning structural and other physical properties about various classes of molecules. They give reasonable bond distances and angles and prevent short van der Waals contacts. Difficulties arise for the prediction of large scale structural elements. These are not only determined by short-range interactions, but also result from long-range electrostatic, hydration, and hydrophobic forces. In the case of the ionically driven DNA B-Z transition, the point of transition as a function of ionic strength and size can be correctly predicted (33). More must be done for a better understanding of the hydration forces (6). What type of questions will be reliably answered by a force-field? Relatively safe answers concern the local geometry of the molecules. If a conformation leads to strong distortions of bond distances or angles or to close van der Waals contacts, it can safely be rejected. Optimizing such unfavorable structures energetically may lead to structures showing how to avoid such distortions. More difficult are energetic questions: Which of two conformers is more stable, or what is the free energy of the substrate in the active site (63)? One cannot always be sure that the force-field provides the correct answers. Therefore, one should concentrate on questions that can be checked experimentally. The application of such concepts to model curved DNA (19, 60) and the DNA four-way junction (61) provides promising results. To explore the knowledge contained in the force-fields, several methods have been proposed. Taking advantage of structural symmetries may improve critically the convergence, while refining the target molecule or its building blocks. A numerically stable derivative for the torsion potential has been proposed. The optimization method of conjugated gradients (see Section II,B) is a powerful tool to find the way downhill toward a local minimum. To surmount barriers and escape local minima requires nonlocal optimization procedures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1410450 TI - [cDNA cloning of galactosyltransferase associated with tumor (GAT)]. PMID- 1410451 TI - [Sialyltransferase--its molecular biology]. PMID- 1410452 TI - [Molecular biology of ABO genes]. PMID- 1410453 TI - [Purification of N-sulfotransferase]. PMID- 1410454 TI - [Genetic regulation of glycolipid expression]. PMID- 1410455 TI - [Erythropoietin]. PMID- 1410456 TI - [The carbohydrate structures of blood coagulation factor VIII]. PMID- 1410457 TI - [Tissue-type plasminogen activator]. PMID- 1410458 TI - [Structures and functional roles of the sugar chains of recombinant cytokines]. PMID- 1410459 TI - [Renin]. PMID- 1410460 TI - [Metastatic phenotype determined by cell surface carbohydrates]. PMID- 1410461 TI - [Heparanases and tumor metastasis]. PMID- 1410462 TI - [Neural cell adhesion molecule: structure and function]. PMID- 1410463 TI - [Role of sugar chains in mammalian fertilization]. PMID- 1410464 TI - [The roles of carbohydrate chain in reproductive and tumor immunology]. PMID- 1410465 TI - [Mechanism for mouse implantation]. PMID- 1410466 TI - [Roles of glycoconjugates in the fertilization of marine invertebrates]. PMID- 1410467 TI - [Carbohydrates in mating of the cellular slime mold]. PMID- 1410468 TI - [Sugars involved in the processes of tumor cell exclusion and inflammatory leukocyte adhesion]. PMID- 1410469 TI - [Carbohydrate recognition system of legume lectins]. PMID- 1410470 TI - [Carbohydrate profiles and disease status in human lung carcinomas]. PMID- 1410471 TI - [Leukemic cell differentiation and glycosphingolipids]. PMID- 1410472 TI - [Cartilage differentiation and its abnormality]. PMID- 1410473 TI - [Tn antigen]. PMID- 1410474 TI - [Gangliosides and cancer-associated antigens]. PMID- 1410475 TI - [Glycolipid in gastric cancer]. PMID- 1410476 TI - [Biogenesis and role of the lysosomal membrane glycoproteins]. PMID- 1410477 TI - [Higher branching of Asn-linked oligosaccharides in relation to tumorigenesis]. PMID- 1410478 TI - [Brain development and proteoglycan]. PMID- 1410479 TI - [Roles of gangliosides on synapse formation]. PMID- 1410480 TI - [Stimulation of neurite-promotion by gangliosides]. PMID- 1410481 TI - [C-series gangliosides and neuronal differentiation]. PMID- 1410482 TI - [Glycoconjugates as developmentally regulated antigens in the central nervous system]. PMID- 1410483 TI - [A novel I-antigen biosynthesis enzyme: a lack of expression in LEC rats]. PMID- 1410484 TI - [Congenital dyserythropoietic anemia type II (HEMPAS)]. PMID- 1410485 TI - [Abnormal sugar chains of IgG in rheumatoid arthritis]. PMID- 1410486 TI - [Alteration in ganglioside of erythrocytes from patients with paroxysmal nocturnal hemoglobinuria]. PMID- 1410487 TI - [Oligosaccharide structures of IgG in multiple myeloma and Castleman's disease]. PMID- 1410488 TI - [Degradation of glycoconjugates in lysosomes and its disorders]. PMID- 1410489 TI - [HIV-infection and N-glycosylation]. PMID- 1410490 TI - [New series of glycosphingolipids in arthropoda]. PMID- 1410491 TI - [Glycolipids of mammalian epidermis]. PMID- 1410492 TI - [KDN: a novel sialic acid analogue]. PMID- 1410493 TI - [Biological function of sulfatide]. PMID- 1410494 TI - [Structural and functional roles of glycosylphosphatidylinositol in membranes]. PMID- 1410495 TI - [Regulation of the biosynthesis of N-glycolylneuraminic acid]. PMID- 1410496 TI - [Transport and metabolism of nucleotide sugars]. PMID- 1410497 TI - [Structural heterogeneity in the carbohydrate-protein linkage region of proteoglycans: working hypothesis on glycosaminoglycan biosynthesis]. PMID- 1410498 TI - [The novel glycosidases acting on proteoglycans]. PMID- 1410499 TI - [New degradation enzyme of mucus glycoprotein]. PMID- 1410500 TI - [Monoclonal antibodies directed to carbohydrate antigens]. PMID- 1410501 TI - [Assay method of glycosidase and glycosyltransferase activities using enzyme linked immunosorbent assay]. PMID- 1410502 TI - [Use of pyridylamino derivatives of sugar chains for substrate specificity of cytosolic alpha-mannosidase]. PMID- 1410503 TI - [Structural analysis of glycolipids by NMR]. PMID- 1410504 TI - [The effect of protein moiety on sugar chain synthesis in a glycoprotein]. PMID- 1410505 TI - [Study on glycosphingolipid functions by using endoglycoceramidase]. PMID- 1410506 TI - [Pathways for syntheses of asparagine-binding and mucin-type carbohydrates]. PMID- 1410507 TI - [Structures of asparagine-binding and mucin-type carbohydrate chains]. PMID- 1410508 TI - [Synthetic pathways and carbohydrate structures of glycolipids]. PMID- 1410510 TI - [Two-dimensional mapping of carbohydrates]. PMID- 1410509 TI - [Synthetic pathways and carbohydrate structures of proteoglycans]. PMID- 1410511 TI - [Protein engineering. I: X-ray crystallographic study of aspartate aminotransferase and its mutant enzymes]. PMID- 1410512 TI - [Protein engineering. II: Catalytic mechanism of aminotransferases]. PMID- 1410513 TI - [Gene mutations in the enzymes involved in lipid metabolism]. PMID- 1410514 TI - [Extracellular matrix and its biological function]. PMID- 1410515 TI - [Multiple principal sigma factors in eubacterial strains]. PMID- 1410516 TI - [Regulation mechanism of spermatogenesis: cell-to-cell interaction in testis]. PMID- 1410517 TI - Development of an animal model of late asthmatic response in guinea pigs and effects of anti-asthmatic drugs. AB - We developed an animal model of late asthmatic response (LAR) in guinea pigs and examined the effects of anti-asthmatic drugs and peptide leukotriene antagonist, MCI-826, on this model. Bronchial challenge of DNP-As (Dinitrophenylated-Ascaris suum extract)-sensitized guinea pigs induced a biphasic increase in pulmonary resistance (RL) with the maximal increase being observed immediately (IAR, immediate asthmatic response) and 3 to 5 hr after antigen inhalation (LAR). Twelve of 22 guinea pigs showed both IAR and LAR. The average increases in RL for all 22 guinea pigs at IAR and LAR, were 168 +/- 13 and 207 +/- 16 (% of baseline value), respectively. Bronchoalveolar lavage (BAL) fluid of guinea pigs that received antigen, revealed increases in the numbers of eosinophils (7.3-fold compared to animals receiving saline) and neutrophils (5.3-fold compared to animals receiving saline) 4 hr after antigen inhalation. When DSCG (disodium cromoglycate) was administered (10 mg/kg, i.v.) before antigen challenge, DSCG significantly inhibited IAR (p less than 0.05) and slightly inhibited LAR (p less than 0.2). Theophylline (30 mg/kg, p.o.) administered before antigen, slightly inhibited both IAR and LAR (p less than 0.2). Salbutamol (3 mg/kg, i.p.) administered before antigen, significantly inhibited IAR (p less than 0.05), but did not affect LAR. These results were correlated with clinical trials. Moreover, peptide leukotriene antagonist, MCI-826, (E)-2,2-Diethyl-3'-[2-[2-(4- isopropyl)thiazolyl] ethenyl]succinanilic acid (0.1 mg/kg, p.o.) administered 1 hr before antigen challenge, significantly inhibited both IAR and LAR (p less than 0.05). MCI-826 (0.1 mg/kg, p.o.) administered 1.5 hr after antigen inhalation, also inhibited LAR (p less than 0.05). Analysis of BAL fluid revealed that DSCG and MCI-826 significantly inhibited the increase in eosinophils (p less than 0.05). These data suggest that leukotriene plays an important role in the development of the pathogenesis of LAR, and that our model is an useful experimental model for investigating the mechanisms of LAR and examining the effects of several anti-asthmatic drugs on LAR. PMID- 1410518 TI - Enhanced thromboxane formation by blood but not whole platelets from spontaneously hypertensive rats. AB - Increased serum levels of immunoreactive thromboxane B2 (iTXB2) were observed in spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Serum iTXB2 levels in whole blood allowed to clot at 37 degrees C for 1 hour were significantly greater in SHR than WKY at 8, 16-20, and 38 weeks of age, whereas formation of iTXB2 by thrombin-stimulated whole platelets from 6 16-week-old SHR and 6 age-matched WKY was 399 +/- 44 and 377 +/- 38 ng/10(9) platelets/30 min, respectively. No significant difference in radioconversion of exogenous arachidonic acid to TXB2 was observed in whole platelets from SHR (18.2 +/- 2.5%, n = 4) and WKY (20.1 +/- 3.0%, n = 4) at 16 weeks of age. These results support the proposal that enhanced ability of blood from SHR to generate iTXB2 is independent of the stage of hypertension development. This enhancement probably depended on factors or blood elements other than platelets since no difference in formation was observed on stimulation of whole platelets. PMID- 1410519 TI - PGE2 secretion from organ cultured gastric mucosa: correlation with cyclooxygenase activity and endogenous substrate release. AB - In gastrointestinal research the in vitro release of prostaglandins from incubated or cultured biopsies is a widely used method to estimate prostaglandin synthesis. We therefore investigated the rate limiting mechanisms of PGE2 release in organ cultured gastric mucosa of the rabbit, determining PGE2 secretion from organ cultured mucosal biopsies by radioimmunoassay and prostaglandin synthesizing capacity by in vitro incubation of mucosal homogenate or microsomes with [14C]-arachidonic acid. Freshly taken biopsies secreted PGE2 at an initial high rate, that decreased during the following 4 hrs of culture. This PGE2 release was dose dependently reduced by inhibitors of the prostaglandin cyclooxygenase. 5mM acetylsalicylic acid (ASA) maximally suppressed PGE2 secretion to 7% of controls, and the inhibition by ASA was quantitatively similar at every given culture period. PGE2 release was markedly increased by carbenoxolone but was only slightly activated by extracellular calcium and the Ca(++)-ionophore A23187. However, Ca++/A23187 were unable to maintain PGE2 secretion at the initial rate. PGE2 secretion was undisturbed in calcium-free medium but was reduced to 50-60% of controls by excess EDTA. The intracellular calcium chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N',-tetraacetic acid acetoxymethyl ester (BAPTA-AM) similarly inhibited PGE2 release to 72% of controls. In contrast, PGE2 release was unaffected by the intracellular calcium antagonist 3,4,5-trimethylene-bis(4-formylpyridinium bromide) dioxime (TMB-8), the calmodulin antagonists N-(6-aminohexyl)-1-5-chloro-1-naphthalenesulfonamide (W-7) and calmidazolium (compound R24571) or various direct inhibitors of endogenous arachidonic acid release like tetracaine, bromophenacyl bromide, neomycin or low dose quinacrine, indicating that the reduction of PGE2 release by EDTA or BAPTA may be mediated by mechanisms different from substrate release. In contrast, an inhibition of PGE2 secretion by quinacrine at high concentrations (greater than or equal to 0.8 mM) was attributed to a direct inhibition of the prostaglandin cyclooxygenase, similar to ASA. Finally, the reduction of the prostaglandin synthesizing capacity by ASA was strongly correlated with the inhibition of PGE2 secretion, also at low concentrations and minor degrees of inhibition. From these data we conclude, that the activity of the prostaglandin cyclooxygenase is rate limiting for PGE2 secretion from organ cultured mucosal biopsies rather than arachidonic acid release by a phospholipase A2. This should be considered for interpretation of studies based on prostaglandin release from cultured mucosa. PMID- 1410520 TI - Prostanoid-induced inhibition of lipolysis in rat isolated adipocytes: probable involvement of EP3 receptors. AB - Sulprostone, enprostil and 16, 16 dimethyl PGE2 have all been found to be potent inhibitors of lipolysis induced by 3-isobutyl-1-methyl-xanthine (IBMX) in rat isolated adipocytes. The potency of sulprostone and enprostil in particular indicates that the response is likely to be mediated through either EP3 or EP1 receptors. However, the EP1-receptor blocking drug, AH6809, had no effect on the antilipolytic response to either PGE2 or sulprostone. We therefore conclude that the receptors mediating prostanoid-induced inhibition of lipolysis in rat adipocytes must principally be of the EP3 sub-type. PMID- 1410521 TI - Secretory diarrhea in villous adenoma of rectum: effect of treatment with somatostatin and indomethacin. AB - The effects of treatment with the synthetic long-acting somatostatin analogue SMS 201-995 were studied in a patient with a fluid and electrolyte secreting villous adenoma of the rectum. The effects of SMS-201-995 on rectal fluid volume and electrolyte loss, and local and general prostanoid production were compared with those of treatment with indomethacin. During treatment with the somatostatin analogue iso-osmolar rectal fluid production increased about 25%; the quantity of prostaglandin E2 in the rectal fluid rose almost 20-fold. Prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha output showed similar, though less impressive increments during somatostatin treatment. The somatostatin analogue did not affect urinary prostanoid excretion except for levels of 2,3-dinor-thromboxane B2, which doubled. With indomethacin treatment diurnal rectal fluid production dropped by about 50% and all prostanoids measured in urine and rectal fluid decreased below control values. It appears that the somatostatin analogue SMS-201-995 has a marked stimulatory effect on the in vivo prostanoid production by the villous adenoma. Perhaps this stimulation is not confined to the tumor only, but also affects thromboxane synthesis. PMID- 1410522 TI - Physiological evidence for the possible existence of anhydrolevuglandin E2-like activity in extracts and media from uteri of rats. AB - Physiological evidence is presented for the possible existence of anhydrolevuglandin E2-like activity in extracts of uteri from diestrous rats and after treatment of adult rats with estradiol and progesterone. The extracts were able to inhibit contractions in rat uterine preparations stimulated by PGE2. Uteri of vaginal Stage 3 (metestrus) were quiescent and showed decreased responsiveness to PGE2 and PGF2 alpha. These uteri showed some contractility when incubation medium from diestrous uteri (Stage 5) were transferred to them and incubation medium from them inhibited the contractility of Stage 5 uteri. When incubation media were exchanged between contractile uteri from of stages other than Stage 3, there was no change in the contraction patterns. Taken together, we believe these data indicate that AnLGE2 may be a normal constituent of the rat uterus and is physiologically increased during Stage 3 (metestrus) of the estrous cycle. PMID- 1410523 TI - Enhanced esterification process of 5-hydroxyeicosatetraenoic acid (5-HETE) in PMN from asthmatic patients. AB - Polymorphonuclear neutrophils (PMN) generate 5-HETE which can be retained within cells as free metabolites or esterified into cellular lipids. Since this metabolite has been shown to have certain inflammatory properties, we compared the generation and distribution profile of 5-HETE in A 23187-stimulated PMN from asthmatic patients (AP) and normal subjects (NS). 5-HETE was analyzed using RP HPLC. After 5 min, total 5 HETE generation was similar in the two populations. However, esterified 5-HETE was significantly enhanced in AP (72 +/- 3% versus 47 +/- 2% of the total synthesis, p less than 0.005), whereas intracellular free 5 HETE was decreased (13 +/- 3% versus 37 +/- 4%, p less than 0.005) and similar low release was observed. Kinetic studies showed that PMN from AP esterified 5 HETE more rapidly and to a greater extent than PMN from NS. By contrast, more intracellular free 5-HETE was recovered in PMN from NS. Esterification seems to be the major pathway of 5-HETE metabolism in PMN from AP. Moreover, we showed that most of the 5-HETE added exogenously was esterified into cellular lipids. In these experimental conditions, PAF-induced migration of PMN was increased. The enhanced ability of PMN to migrate could be due to the increase of 5-HETE esterification process. PMID- 1410524 TI - Dual metabolic pathways of 12-HETE in rat aortic smooth muscle cells. AB - 12(S)-HETE, a major lipoxygenase-derived compound from arachidonic acid is incorporated and metabolized by vascular smooth muscle cells via beta-oxidation. We have now identified for the first time in this cell type 12(S)-HETE metabolites formed by a combination of reductase and oxidation pathways. HPLC and GC-MS analysis of time-course experiments allow us to characterize two different metabolic pathways: a direct peroxisomal beta-oxidation of 12(S)-HETE leading to the formation of 16:3 (8-OH) which accumulates first and a reduction of one of the conjugated double bonds of 12(S)-HETE giving the dihydro-intermediate 20:3(12 OH) that transiently accumulates before being converted itself by peroxisomal beta-oxidation to 16:2(8-OH). Taken together these results may suggest that the transient accumulation of 20:3(12-OH) through transcellular metabolism of 12(S) HETE may represent a part of the modulatory effect of 12(S)-HETE on vascular function. PMID- 1410525 TI - Limited utilization of exogenous arachidonic acid by the prostaglandin cyclooxygenase in gastric mucosa: the role of protein binding, glutathione peroxidase, and hydrogen peroxides. AB - We investigated the utilization of exogenous 14C-labelled arachidonic acid by the cyclooxygenase system of the gastric mucosa and its alteration by cytosolic factors, protein binding, glutathione peroxidase (GSH-Px), and hydrogen peroxides. Total prostaglandin (PG) synthesis from gastric microsomes was reduced in a dose- dependent manner to 12% and 68% of controls by increasing amounts of the 105,000g supernatant or albumin (8mg protein/ml), respectively (p less than 0.01). The inhibitory cytosolic factor was heat labile, protease sensitive, and was retained by a 300,000 Dalton ultrafiltration membrane. Thus, it was likely a protein. Other possible inhibitory mechanisms like protease- or heme-induced destabilization of the cyclooxygenase, haptoglobin-mediated inhibition, or self inactivation by endogenous substrate were excluded. N-ethylmaleimide (NEM), an agent that alkylates sulfhydryl-groups thereby inhibiting GSH-Px, abolished the inhibitory effect of cytosol in a dose-dependent fashion. In contrast to their inhibition of prostaglandin synthesis, the binding of arachidonic acid by albumin or cytosolic proteins accounted to 75% and 19% under comparable conditions, respectively, however, cytosolic fatty acid binding was unaffected by NEM. Thus, it was concluded that the inhibitory effect of cytosol, in contrast to albumin, was mediated by a sulfhydryl-depending process, probably a GSH-Px. This conclusion was supported by a qualitatively comparable inhibition by a purified GSH-Px from bovine erythrocytes. The inhibitory action of cytosolic proteins was reduced significantly by increasing concentrations or repeated application of arachidonic acid; therefore, cytosolic GSH-Px was likely to affect substrate utilization by the microsomal PGH synthase through reduction of activating substrate peroxides. Similarly, the in vitro formation of cyclooxygenase products by mucosal homogenate or gastric microsomes in the absence of cytosol was limited at substrate concentrations below 80 microM, despite sufficient nonesterified arachidonic acid remaining in the incubate. This limitation was mediated only partially by self-inactivation of the prostaglandin cyclooxygenase. Neither N ethylmaleimide nor repeated application of hydrogen peroxides increased substrate utilization by isolated microsomes, excluding contamination by GSH-Px or simply a lack of hydrogen peroxides as possible mechanisms for the limited utilization. From these results, a special role of substrate-linked lipid peroxides in the activation of mucosal prostaglandin synthesis is proposed. The reduction of these peroxides by glutathione dependent or independent peroxidases, e.g. the PGH synthase-linked hydroperoxidase activity itself, could explain the reduced utilization of nonesterified arachidonic acid by the gastric mucosa. PMID- 1410526 TI - Relationships among mammalian gonadotropin-releasing hormone, prostaglandins, and sex steroids in the brain of the crested newt, Triturus carnifex. AB - The present study was carried out to evaluate the in vitro brain release of prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), androgens, and 17 beta-estradiol in male and female crested newt, Triturus carnifex, during three different periods of the annual sexual cycle; in addition, the effects of mammalian gonadotropin-releasing hormone (mGnRH), PGF2 alpha, and PGE2 on prostaglandins and steroids release by the brain were evaluated during the same periods. In brain incubations of both sexes, PGF2 alpha and estradiol were higher during postreproduction, while PGE2 and androgens were higher during reproduction. In both sexes, mGnRH increased PGF2 alpha and estradiol during postreproduction, and PGE2 during reproduction; PGF2 alpha increased estradiol secretion during postreproduction. Only in the male, did both mGnRH and PGE2 increase androgens during reproduction. It could be suggested that in Triturus carnifex, the regulation of the reproductive activity in the central nervous system (CNS) depends on the relationships among mGnRH, prostaglandins and steroids. In particular, PGF2 alpha and PGE2 seem to play different roles in the CNS of the newt: PGF2 alpha is involved in the postreproductive processes, through estradiol secretion, while PGE2 in the reproductive ones (through androgens secretion?). PMID- 1410527 TI - Platelet activation and prostacyclin release in essential hypertension. AB - To evaluate platelet activation thromboxane A2 (TxA2) and beta-thromboglobulin (beta TG) were used as markers and in addition we studied the biosynthesis of prostacyclin. Synthesis of TxA2 and prostacyclin was assessed by measurement of urinary metabolites. Fifteen untreated hypertensive patients (HT) and 15 age matched normotensive controls (NT) were investigated at rest, during and after exercise. HT patients were re-examined after 3 months on enalapril. During basal conditions there was no difference in the excretion of Tx-M, PGI-M or beta TG between the groups. During strenuous exercise HT exhibit a significantly higher increase in prostacyclin synthesis (162%) compared to NT (76%). The levels of beta TG increased with 82% in the HT and 24% in the NT group, Tx-M increased with 27% and 23% respectively. Treatment with the ACE-inhibitor enalapril did not significantly alter these findings. These results indicate that there is no evidence of basal platelet activation in early essential hypertension. Strenuous exercise leads to some increase in Tx-M in both groups, with no pronounced differences between the groups. Hypertensive patients exhibit a significantly increased prostacyclin response to exercise which could be due to differences in vessel-wall reactivity. Enalapril seems to exert no effect on platelet activation or on prostacyclin biosynthesis. PMID- 1410529 TI - Opioid peptides are substrates for the bifunctional enzyme LTA4 hydrolase/aminopeptidase. AB - We determined if any naturally occurring peptides could act as substrates or inhibitors of the bifunctional, Zn2+ metalloenzyme LTA4 hydrolase/aminopeptidase (E.C.3.3.2.6). Several opioid peptides including met5-enkephalin, leu5 enkephalin, dynorphin1-6, dynorphin1-7, and dynorphin1-8 competitively inhibited the hydrolysis of L-proline-p-nitroanilide by leukotriene A4 hydrolase/aminopeptidase, consistent with an interaction at its active site. The enzyme catalyzed the N-terminal hydrolysis of tyrosine from met5-enkephalin with Km = 450 +/- 58 microM and Vmax = 4.9 +/- 0.6 nmol-hr-1-ug-1 and from leu5 enkephalin with Km = 387 +/- 90 microM and Vmax = 6.2 +/- 2.5 nmol-hr-1-ug-1. Bestatin, captopril and carnosine inhibited the hydrolysis of the enkephalins. It is noteworthy that the bifunctional catalytic traits of this enzyme include generation of an hyperalgesic substance, LTB4, and inactivation of analgesic opioid peptides. PMID- 1410528 TI - Proinflammatory cytokines interact synergistically with epidermal growth factor to stimulate PGE2 production in amnion-derived cells. AB - Recent evidence has implicated cytokines and growth factors in the initiation of parturition in women. In the present study, the amnion-derived cell line WISH was used to determine whether proinflammatory cytokines (interleukins 1 beta, 6, and 8, tumor necrosis factor-alpha, and granulocyte/macrophage colony stimulating factor) could amplify epidermal growth factor-induced prostaglandin E2 production. WISH cells were preincubated with cytokines (0.0001-10 ng/ml) for 60 min and then challenged with EGF (10 ng/ml) for 4 hrs after which PGE2 production was measured by radioimmunoassay. EGF, IL-1 beta and TNF-alpha alone caused a dose-dependent increase in PGE2 production, while IL-6, IL-8 and GM-CSF were ineffective over the dose range tested. When cells were preincubated with IL-1 beta or TNF-alpha, there was a dose-dependent potentiation of EGF-induced PGE2 production that was greater than the sum of EGF alone and IL-1 beta or TNF-alpha alone. In each case, the minimum dose of IL-1 beta or TNF-alpha which amplified EGF-induced PGE2 production was 0.1 ng/ml (p less than 0.05, Student's t-test). These data show that low concentrations of IL-1 beta or TNF-alpha may serve to amplify EGF-mediated PGE2 biosynthesis in amnion-derived cells and suggest that cytokines may modulate EGF function in responsive cells. PMID- 1410530 TI - [Dumb August. Freud's "dream interpretation" as a critique of traditional common sense]. AB - Freud's profound scepticism about philosophy and its fondness for philosophical "systems" is well-known. From an early stage, the author of the "Interpretation of Dreams" was convinced that philosophy--like animism--was nothing other than a narcissistic attempt to explain the world systematically from one single point. That point is the ego, synthesising everything manifold, alien and threatening into an intelligible mould and subjecting it to the intellectual censorship of the cogito. Gekle shows that Freud's "Interpretation of Dreams" undercuts and decentralizes the imperialist claims of the ego, thus opening up vistas on the areas where the ego is not sole and undisputed master. At the same time, however, it becomes apparent that the decentralizing work of dream interpretation is itself confronted by a paradox. The insights gained in the process cannot be presented in any other than a theoretical, systematic and hence ego-oriented form. PMID- 1410531 TI - [Signs of change in the affective context of dreams and the psychoanalytic process]. AB - The author inquires whether dreams related in psychoanalysis can be indicator of curative change, and if so what affective conditions go to making this possible. To answer this question convincingly, he puts forward a new model of dream generation. It proceeds from the relation between cognitive elements, regulatory affective processes and species of interaction represented in individual dream situations. Such a model requires a new theory of mental representation, affective processes and memory. For precise analysis of change processes, Moser has recourse to a coding system for dream content. Finally he compares change processes in dreams with those in the psychoanalytic situation and suggests hypotheses on the extent to which changes in dreams can be indicators of changes in the psychoanalytic process. PMID- 1410532 TI - [The functional correlations of dreams and transference]. AB - The author discusses the old question about an exceptional position of the dream in psychoanalysis in a new way: he postulates the exceptional position of the dream in relation to the transference. Case material is given to illustrate how the dream report goes beyond the level of information insofar it is in itself equivalent to a specific ongoing of the transference process. In conclusion the relations between dream and transference are discussed in regard to a hypothetic functional unit. PMID- 1410533 TI - [Father and daughter: identifying with difference. A contribution to sexual heterodoxy]. PMID- 1410534 TI - [Historical identity and the identity of the historian]. PMID- 1410535 TI - [Freud in the USSR. Psychoanalysis can only develop in a free state. Freud's works now becomes public in Russia]. PMID- 1410537 TI - Somatization. PMID- 1410536 TI - Challenges of somatization: diagnostic, therapeutic and economic. PMID- 1410538 TI - Medicolegal aspects of factitious disorder. PMID- 1410539 TI - Psychological appraisal and emotional response to physical injury: a clinical, phenomenological study of 109 adults. AB - We studied the cognitive, emotional and behavioral responses at four points of time in a random sample of 109 accidentally injured adults via audio taped semistructured interviews and self-assessment rating scales. Neither the subjects appraisal of death or disability, nor the emotional responses corresponded strongly to the severity of the physical injury sustained or the "objective" threat to life but, instead, reflected, to a large extent, the personal meaning of the injury or the accident. Dissociative responses reported by 17 persons were of short duration and associated with young age and immaturity, and did not predict or a poor longterm post-traumatic psychiatric course. Ratings of intrusion, avoidance and anxiety were more strongly associated with psychopathology than "objective" danger or injury severity. This study indicates that following civilian trauma, the cognitive, emotional and behavioral responses are strongly related to preaccident and accident-independent life circumstances. The findings question the validity of the DSM-IIIR criterion of stressors of PTSD in civilian accidents, and suggest that post-traumatic mental disorders should be evaluated in much the same way as psychiatric disorders after physical illness. PMID- 1410540 TI - Somatization in child, adolescent and family psychiatry. PMID- 1410541 TI - Coping with accidental injury. AB - Coping styles and perceptual defense were studied in 20 accidentally injured adult males during hospital stay and 28 months later via clinical psychiatric and surgical examinations, the Comprehensive Psychopathological Rating Scale, Ways of Coping Checklist, Impact of Event Scale, Basic Character Inventory, the Multidimensional Health Locus of Control Scale, State Anxiety Inventory and Defense Mechanism Test. Coping styles, particularly emotion-focused coping, were more strongly correlated with underlying psychopathology than with severity of injury. Coping styles remained stable during the period of study and did not correlate with perceptual defense, state anxiety, personality traits or symptoms of post-traumatic stress. However, six specific coping efforts predicted patients who suffered from short- and long-term negative consequences with a specificity and positive predicting power of 100% and sensitivity of 69%. Results correspond to previous studies of coping with chronic illness, and suggest that somatization following physical trauma is better explained with reference to personal meaning than to a fright-model as suggested in the post-traumatic stress criteria of the DSM-III-R. PMID- 1410542 TI - Building a psychiatric-medical liaison: observations of the process. PMID- 1410543 TI - Somatization in the elderly. PMID- 1410544 TI - Family psychiatric history of patients with somatization disorder. AB - We estimated the prevalence of psychiatric disability and disorders (depression, mania, schizophrenia, alcohol disorder, drug disorder, antisocial personality, and somatization) in the parents, siblings, and children of three groups of index cases: primary care patients with somatization disorder (n = 70), primary care patients who approached, but did not reach, DSM-III-R criteria for somatization disorder (n = 29), and randomly-selected community residents with no psychiatric disorder (n = 1633). Nearly all psychiatric disorders were more common in relatives of both patient samples than in relatives of community residents, and the patient samples rarely differed from each other. In the patient samples, the 22.9% rate of patients with multiple unexplained medical problems is substantially higher than previous investigations of somatization would predict. The most common disorders in patients' relatives were depression and alcohol disorder. There was little difference in the rates of depression in relatives of somatization patients who were or were not themselves depressed. A similar pattern occurred for alcohol disorder. There was a high risk for antisocial personality disorder in parents of patients meeting DSM-III-R criteria for somatization disorder, but this increase was not found for other relatives. PMID- 1410545 TI - Psychiatric disorder and functional somatic symptoms as predictors of health care use. AB - Data from Wave 1 of the National Institute of Mental Health Epidemiologic Catchment Area study were used to examine how functional somatic symptoms and other psychiatric disorders relate to use of health care. Panic disorder and functional somatic symptoms were strongly linked to use of general medical services while depression showed such a relationship only among females. Panic disorder and depression also showed strong association with use of mental health services, but functional somatic symptoms showed only a weak relationship. Multivariable models suggest that functional somatic symptoms lead to selective use of general medical services over mental health services. PMID- 1410546 TI - Somatization, co-morbidity, and the quality of life: measuring the effect of depression upon chronic medical illness. PMID- 1410547 TI - Somatization and pulmonary disease. PMID- 1410548 TI - Pseudosomatization. PMID- 1410549 TI - Nurse practitioners hampered. PMID- 1410550 TI - The career structure--some questions answered. PMID- 1410551 TI - Regionalisation and the community nurse. PMID- 1410552 TI - Occupational asthma. PMID- 1410553 TI - A decision for enrolled nurses. PMID- 1410554 TI - Articulatory and phonological determinants of word length effects in span tasks. AB - Several previous studies have shown that memory span is greater for short words than for long words. This effect is claimed to occur even when the short and long words are matched for the number of syllables and phonemes and so to provide evidence for subvocal articulation as being one mechanism that underlies memory span (Baddeley, Thomson, & Buchanan, 1975). The three experiments reported in this paper further investigate the articulatory determinants of word length effects on span tasks. Experiment 1 replicated Baddeley et al.'s finding of an effect of word length on auditory and visual span when the stimuli consist of words that differ in terms of the number of syllables. Experiments 2 and 3 showed that the effects of word length are eliminated when the words in the span task are matched for the number of syllables and phonemes but differ with respect to the duration and/or complexity of their articulatory gestures. These results indicate that it is the phonological structure of a word and not features of its actual articulation that determines the magnitude of the word length effect in span tasks. PMID- 1410555 TI - Saccadic eye movements in Parkinson's disease: I. Delayed saccades. AB - The saccadic eye movements of nine patients with Parkinson's disease were compared to those of nine age-matched controls in two paradigms generating volitional saccades. In both paradigms, subjects had to make delayed saccades to peripheral LED targets: a peripheral target appeared 700 msec before a buzzer sounded, the buzzer being the signal to make a saccade to the target. In the first paradigm ("centre-off"), the fixation target was extinguished simultaneously with buzzer onset. In the second ("centre-remain") it was not extinguished until 1000 msec later. The results showed that for outward saccades in both paradigms, there was no difference between Parkinsonian patients and controls, but saccadic latencies were significantly shorter in the "centre remain" paradigm. The initial outward saccades were indistinguishable from the normal, reflex saccades of the same subjects. However, saccades returning to the centre (a type of remembered target saccade) were hypometric and showed multistepping. Both effects were more pronounced in patients with Parkinson's disease. The significance of these findings in terms of current hypotheses about the nature of the Parkinsonian saccadic deficit is discussed. PMID- 1410556 TI - Saccadic eye movements in Parkinson's disease: II. Remembered saccades--towards a unified hypothesis? AB - Ten patients with mild to moderate Parkinson's disease were compared with ten age matched normal controls in a series of saccadic paradigms in order to test various hypotheses relating to the origin of the Parkinsonian saccadic defect. The paradigms comprised a reflex saccade paradigm, a standard remembered saccade paradigm, a remembered saccade paradigm with delayed centre-offset, and a remembered saccade paradigm with a second target flash immediately prior to saccade execution. Finally, subjects executed both reflex and remembered saccades in a standard remembered paradigm (the "two-saccade" paradigm). As has been reported previously, Parkinsonian subjects demonstrated hypometria on all remembered saccade paradigms, particularly the "two-saccade" paradigm. There was, however, no significant difference between the first three remembered saccade paradigms. These studies serve to refute a simple attentional capture hypothesis, and a hypothesis that suggests that the abnormality of remembered saccades is due to concurrent reflex saccade suppression. On the basis of the results, further hypotheses are advanced in an attempt to explain all published work on Parkinsonian saccades. PMID- 1410557 TI - On the relation between time perception and the timing of motor action: evidence for a temporal oscillator controlling the timing of movement. AB - Studies of time estimation have provided evidence that human time perception is determined by an internal clock containing a temporal oscillator and have also provided estimates of the frequency of this oscillator (Treisman, Faulkner, Naish, & Brogan, 1990; Treisman & Brogan, 1992). These estimates were based on the observation that when the intervals to be estimated are accompanied by auditory clicks that recur at certain critical rates, perturbations in time estimation occur. To test the hypothesis that the mechanisms that underlie the perception of time and those that control the timing of motor performance are similar, analogous experiments were performed on motor timing, with the object of seeing whether evidence for a clock would be obtained and if so whether its properties resemble those of the time perception clock. The prediction was made that perturbations in motor timing would be seen at the same or similar critical auditory click rates. The experiments examined choice reaction time and typing. The results support the hypothesis that a temporal oscillator paces motor performance and that this oscillator is similar to the oscillator underlying time perception. They also provide an estimate of the characteristic frequency of the oscillator. PMID- 1410558 TI - Amnesics have a disproportionately severe memory deficit for interactive context. AB - Two experiments were used to compare the recognition memory of amnesic and normal subjects for intentionally encoded words (targets) and for incidentally encoded words that were meaningfully related to the targets and presented at the same time (interactive context). In both experiments the target recognition of the two groups was matched at a high level by presenting the amnesics with much shorter lists of words to remember. Experiment 1 compared 20 amnesics and their matched controls and showed that whereas the amnesics' recognition of the target words did not benefit significantly when they were presented together with their interactive context words (relative to their recognition when the target words were presented alone), that of the controls did. Experiment 2 compared 14 amnesics and their matched controls and showed that when patients and their controls were matched on their target word recognition in isolation, then the patients still showed worse recognition for the interactive context words. These effects were not found only in Korsakoff patients, and their size did not correlate with behavioural measures of frontal-lobe damage. It is concluded that amnesics may be more impaired at recognizing incidentally encoded interactive context than they are at recognizing target material, and this deficit may be an essential feature of the syndrome. PMID- 1410559 TI - A dynamical systems approach to skill acquisition. AB - This paper argues that the answer to the question, what has to be learned, needs to be established before the question, how is it learned, can be meaningfully addressed. Based on this conviction, some of the limitations of current and past research on skill acquisition are discussed. Motivated by the dynamical systems approach, the question of "what has to be learned" was tackled by setting up a non-linear mathematical model of the task (i.e. learning to make sideways movements on a ski apparatus). On the basis of this model, the phase lag between movements of the platform of the apparatus and the actions of the subject was isolated as an ensemble variable reflecting the timing of the subject in relation to the dynamics of the apparatus. This variable was subsequently used to study "how" the task was learned in a discovery learning experiment, in which predictions stemming from the model were tested and confirmed. Overall, these findings provided support for the hypothesis, formulated by Bernstein (1967), that one of the important effects of practice is learning to make use of reactive forces, thereby reducing the need for active muscular forces. In addition, the data from a previous learning experiment on the ski apparatus--the results of which had been equivocal--were reconsidered. The use of phase lag as a dependent variable provided a resolution of those findings. On the basis of the confirmatory testing of predictions stemming from the model and the clarification of findings from a previous experiment, it is argued that the dynamical systems approach put forward here provides a powerful method for pursuing issues in skill acquisition. Suggestions are made as to how this approach can be used to systematically pursue the questions that arise as a natural outcome of the experimental evidence presented here. PMID- 1410560 TI - Imaging in cardiac mass lesions. AB - In 26 patients with cardiac mass lesions confirmed by surgery, diagnostic imaging was performed preoperatively by means of two-dimensional echocardiography (26 patients), angiography (12 patients), correlative computed tomography (CT, 8 patients), and magnetic resonance imaging (MRI, 3 patients). Two-dimensional echocardiography correctly identified the cardiac masses in all patients. Angiography missed two of 12 cardiac masses; CT missed one of eight. MRI identified three of three cardiac masses. Although the sensitivity of two dimensional echocardiography was high (100%), all methods lacked specificity. None of the methods allowed differentiation between myxoma (n = 13) and thrombus (n = 7). Malignancy of the lesions was successfully predicted by noninvasive imaging methods in all six patients. However, CT and MRI provided additional information concerning cardiac mural infiltration, pericardial involvement, and extracardiac tumor extension, and should be integrated within a preoperative imaging strategy. Thus two-dimensional echocardiography is the method of choice for primary assessment of patients with suspected cardiac masses. Further preoperative imaging by CT or MRI can be limited to patients with malignancies suspected on the grounds of pericardial effusion or other clinical results. PMID- 1410561 TI - Multi-directional positron imaging: evaluation of cancer detection with 2-(F-18) fluoro-2-deoxy-D-glucose. AB - We developed a multi-directional positron imaging system for the whole body in order to evaluate the spatial distribution of radiopharmaceuticals. A positron emission tomography (PET) scanner with ring detectors was modified to provide 54 directional planar images with a three-dimensional appearance by using cinematic display. The initial clinical evaluation was performed on two normal volunteers and 17 cancer patients with 32 foci. Images were obtained approximately one hour after the intravenous administration of 2-(F-18)-fluoro-2-deoxy-D-glucose. In all 19 subjects, good quality images with a three-dimensional appearance were obtained. We were able to visualize 16 of 20 (80%) lesions that were three centimeters or more in greatest diameter. In contrast, only seven of 12 (58%) lesions less than three centimeters in greatest diameter were identified. The overall detectability of lesions was 72%. These results suggest that this system will be useful for tumor detection. PMID- 1410562 TI - Influence of matrix size, vessel shape, vascular diameter, flow velocity, course of vessels on MR angiography. AB - Basic experiments were done to examine the influence of the extent of curve, direction of flow, vascular diameter, velocity of flow, and course of vessels on MR angiography. In the first experiment, two phantoms were constructed of vinyl tubing, a hairpin type and one with tubes bent to varying degrees. These phantoms were imaged in two matrices, different FOV, and of various velocities with a 1.5 Tesla system. Images of a normal volunteer were also obtained. In studies of the hairpin phantoms, a low intensity artifact appeared at the curve position, and the edge became fuzzy when the flow was perpendicular to the phase encoding direction. These phenomena were more apparent with a smaller matrix, smaller FOV, more gentle angle, larger diameter, and faster flow; in other words the component along the direction was dominant. In the phantom that used bent tubes, another low intensity artifact appeared on the medial side of the outflow portion. The results obtained from the volunteer corresponded well to those from the basic experiments. It was thought that the profile of flow was not well demonstrated due to the coarse matrix. In the second experiment, water flowed at various speeds through three-dimensional phantoms that were made of vinyl tubes of various diameters and directions. The phantoms were imaged with two- and three dimensional time of flight and phase contrast angiography. The lower limits of detection of the phase contrast method were almost the same. In the coronal plane, the lower limit decreased to 2.5 mm for arteries and 9.5 mm for veins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410563 TI - Atypical arteriographic features of myositis ossificans circumscripta (MOC). AB - Earlier reports on the angiographic features of MOC concluded that there may be hypervascularity and tumor stain but no A-V shunting, pooling, or vessel amputation as a result of the lesion. However, our cases demonstrated A-V shunting in MOC, and showed that the vascularity of this lesion can closely mimic that of malignant neoplasms. Therefore, the possibility of MOC should not be excluded because of the presence of A-V shunts or "tumor vessels" in suspected MOC lesion on plain radiography. These points are underscored by the findings in two MOC patients, whose cases are described. PMID- 1410564 TI - A Japanese adult case of cystic fibrosis causing bone demineralization. AB - Cystic fibrosis is an inherited, multisystem disorder characterized by an abnormality in exocrine gland function. It leads to chronic pulmonary disease in most cases and pancreatic insufficiency in 85 percent of patients. Although this disease is not uncommon in Caucasians, it has been considered very rare among Japanese. The majority of patients are diagnosed in infancy or childhood. The patient in this case report was a 45-year-old Japanese man who had not been diagnosed as having cystic fibrosis. This patient had recurrent episodes of pulmonary infection that started in childhood, and plain films of the chest showed increased interstitial markings, hyperaeration, and bronchiectasis. CT of the upper abdomen showed a generally enlarged pancreas with complete fatty replacement. Serum and urine pancreatic enzyme levels were low, suggesting pancreatic insufficiency. Repeated sweat tests were positive. A roentgenologic skeletal survey showed general demineralization, which may be multifactorial. In this case, it was concluded that vitamin D deficiency caused by vitamin D malabsorption and/or insufficient sunlight exposure was mainly responsible for the demineralization and that chronic respiratory acidosis might also be partially responsible. PMID- 1410565 TI - Unusual complication of liver irradiation: acute thrombosis of a main hepatic vein: CT and MR imaging features. AB - The pathologic changes resulting from liver irradiation include congestion, fibrosis, and veno-occlusive disease. We report an unusual complication of radiation induced injury: acute thrombosis of a main hepatic vein within the radiation port. CT and MR features are described and the etiology of this unusual complication is discussed. PMID- 1410566 TI - Computed tomographic findings of small-bowel volvulus. AB - Computed tomographic examinations of two cases of small-bowel volvulus were reviewed. At laparotomy, both cases were proved to be secondary to adhesions. CT examinations showed focal, wedge-shaped, edematous mesentery with trapped fluid between mesenteric folds radiating toward the site of torsion. One case showed the superior mesenteric vein spiraling around the superior mesenteric artery. At laparotomy, affected small-bowel loops showed ischemia in both cases. CT performed in patients with acute abdomen may show findings suggestive of small bowel volvulus. PMID- 1410567 TI - Dosimetry of intracavitary placements for uterine and cervical carcinoma: results of orthogonal film, TLD, and CT-assisted techniques. AB - A total of 720 192Ir high-dose-rate (HDR) applications in 331 patients with gynecological tumors were analyzed to evaluate the dose to normal tissues from brachytherapy. Based on the calculations of bladder base, bladder neck, and rectal doses derived from orthogonal films the planned tumor dose or fractionation was altered in 20.4% of intracavitary placements (ICP) for cervix carcinoma and 9.2% of ICP for treatment of the vaginal vault. In 13.8% of intracervical and 8.1% of intravaginal treatments calculated doses to both the bladder and rectum were greater than or equal to 140% of the initially planned dose fraction. Doses at the bladder base were significantly higher than at the bladder neck (p less than 0.001). In 17.5% of ICP the dose to the bladder base was at least twice as high as to the bladder neck. The ratio of bladder base dose to the bladder neck was 1.5 (+/- 1.19 SD) for intracervical and 1.46 (+/- 1.14 SD) for intravaginal applications. The comparison of calculated doses from orthogonal films with in-vivo readings showed a good correlation of rectal doses with a correlation coefficient factor of 0.9556. CT-assisted dosimetry, however, revealed that the maximum doses to bladder and rectum were generally higher than those obtained from films with ratios of 1-1.7 (average: 1.44) for the bladder neck, 1-5.4 (average: 2.42) for the bladder base, and 1.1-2.7 (average: 1.37) for the rectum. When doses to the specified reference points of bladder neck and rectum from orthogonal film dosimetry were compared with the corresponding points on CT scans, similar values were obtained for both methods with a maximum deviation of +/- 10%. Despite the determination of multiple reference points our study revealed that this information was inadequate to predict doses to the entire rectum and bladder. If conventional methods are used for dosimetry it is recommended that doses to the bladder base should be routinely calculated, since single point measurements at the bladder neck seriously underestimate the dose to the bladder. Also the rectal dose should be determined at several points over the length of the implant due to the wide range of anatomic variations possible. PMID- 1410568 TI - A comparison of accuracy of computer treatment planning systems in brachytherapy. AB - An intercomparison was made between dose-rate point calculations with five commercial computer treatment planning systems used in brachytherapy. Sixteen Italian radiotherapy medical physics institutions performed a twofold test, respectively for point and linear sources, reproducing actual clinical implants and the results were compared to references values. The test was designed in order to determine the errors introduced separately by computation and by implant reconstruction via orthogonal films. The results show that for point sources a better accuracy can be achieved than for linear sources. It is also shown that a large variation of results exists between computation systems and the variability is larger for linear sources. The digitizing procedure adds a large amount of error. In the whole set of calculation points, the overall percent difference between computed and reference dose-rate values is larger than +/- 5% in 18% cases for point and in 52% cases for linear sources, with data input by digitizer. It seems that relevant errors do occur when computing actual dose rates, resulting in clinically relevant inaccuracies in the calculated absorbed dose and in its relative effectiveness. PMID- 1410569 TI - Clinical experience with a single field rotational total skin electron irradiation technique for cutaneous T-cell lymphoma. AB - Between October 1981 and December 1989, 44 patients with cutaneous T-cell lymphoma (CTCL) were treated with a single field rotational total skin electron irradiation (RTSEI) technique developed in the McGill University, Department of Radiation Oncology. Only 11 (25%) of the 44 patients had received no prior treatment. Three-quarters (33/44) had advanced (T3 or T4) disease. Complete responses were seen in 32/44 (73%) of patients (91% T2, 71% T3 and 58% T4), but only 3/11 (27%) of patients with T2 disease and 3/21 (14%) of patients with T3 disease remain in continuous complete remission in the skin, after median intervals of 58 and 35 months, respectively. Median cause-specific survival for the whole group is 43 months and survival at 5 years is 38%. Survival was significantly better for patients with T2 disease than for patients with T3 disease (relative risk 4.3; 95% CI 1.4-13.2) and patients with T4 disease (relative risk 3.1; 95% CI 0.8-12.1). The RTSEI technique used at McGill has depth-dose characteristics and photon contamination similar to other commonly used TSEI techniques. It is relatively simple and provides a homogenous dose distribution over the entire skin surface in a short treatment time. Results of treatment are similar to those obtained with other techniques. For T2 disease, TSEI is an effective treatment modality with a possibility of long-term tumor control. For more advanced disease, more aggressive treatment, which may include TSEI, is necessary. PMID- 1410570 TI - Carcinomas of the nasal cavity. AB - Between 1969 and 1985, 45 patients with carcinomas of the nasal cavity proper received curative treatment. Thirty patients had squamous cell carcinoma, one had undifferentiated carcinoma, 9 had adenocarcinoma, and 5 had adenoid cystic carcinoma. Eighteen patients were treated with definitive radiotherapy (interstitial brachytherapy in 5 and external beam therapy in 13 patients), and 27 received surgery and radiotherapy. The median length of follow-up was 11 years (range: 2.8-16.8 years). Thirty-six patients had no evidence of disease at the last follow-up visit. All 14 patients with carcinoma of the nasal septum had the disease controlled. Nine of 31 patients with lesions of the lateral wall and floor died of the disease, 5 of uncontrolled local disease, 2 of distant metastases, and 2 of both. The disease-specific survival rates at 5 and 10 years were 83 and 80%, respectively, and the corresponding overall survival rates were 75 and 60%, respectively. Blindness occurred in 4 patients, 2 due to orbital exenteration and 2 to radiation injury to the cornea and optic pathway. Other infrequent side effects were bone necrosis, dental decay, nasal stenosis, and septal perforation. This study indicated that the prognosis of patients with nasal cavity carcinoma was better than that of patients with maxillary sinus cancer treated during the same era. In addition, the study showed that carcinomas of the nasal septum were smaller than those of lateral wall and floor at diagnosis, so that excellent control could be achieved by definitive radiotherapy; when accessible, interstitial brachytherapy might be the treatment of choice in such patients. PMID- 1410571 TI - The effect of unlabelled monoclonal antibody (mAb) on the biodistribution of 131I anti-idiotype mAb in murine B cell lymphoma. AB - The 38C13 murine B cell lymphoma model was used to study the effect of the preinjection of unlabelled anti-idiotype monoclonal antibody (mAb) on the subsequent biodistribution of 131I-anti-idiotype mAb. Mice with established tumors received 0-500 micrograms of unlabelled anti-idiotype mAb 24 h prior to the administration of 131I-anti-idiotype (specific), or both 125I-anti-idiotype and 131I-isotype-matched irrelevant control (nonspecific) mAb. Mice were counted daily in a gamma counter and sacrificed at 2-144 h following injection. Mice were dissected and the weight and activity of the animals and organs were measured. Mice were bled periodically and circulating idiotype levels were measured using an ELISA assay. Five hundred micrograms of unlabelled anti-idiotype mAb increased the retention time of the specific but not the nonspecific mAb in all organs and tumor. Following pretreatment with unlabelled mAb, the cumulative tumor/whole body and tumor/normal organ ratios became similar to those of the nonspecific mAb, with concentration ratios (specific/nonspecific mAb) of approximately 1, which persisted until 96 h post injection when circulating idiotype reappears in antigen excess. In the absence of unlabelled mAb there was less retention in tumor and normal tissue. This is presumed to be due in part to decreased levels of circulating 131I-mAb secondary to rapid plasma clearance of antigen-antibody complexes and tumor cell mediated dehalogenation, which results when the specific mAb specifically binds the targeted antigen. Thus, the addition of unlabelled mAb increased the retention by decreasing the specific behavior of the anti-idiotypic antibody. PMID- 1410572 TI - Mouse hemithoracic irradiation and its interaction with cytotoxic drugs. AB - Irradiation of the mouse right or left hemithorax at 14 or 18 Gy produced a dose dependent rise in breathing rate 16 weeks after irradiation without significant mortality. The measurement of breathing rate changes following right hemithoracic irradiation combined with the maximally tolerated dose of cytotoxic drugs was assessed as a method for qualitatively detecting drug-irradiation interactions which either exacerbate pneumonitis or alter its time course. Cyclophosphamide at 100 mg/kg accentuated and accelerated the rise in breathing rate, culminating in early mortality. BCNU 30 mg/kg delayed the appearance of the radiation response. Busulphan 30 mg/kg appeared to be radioprotective, but this was shown to be due to the DMSO-containing vehicle. Doxorubicin 6 mg/kg had no effect when combined with right or left hemithoracic irradiation. Carboplatin 100 mg/kg, vindesine 4 mg/kg and vinblastine 4 mg/kg had no substantial effect upon the changes in breathing rate. PMID- 1410573 TI - The use of large fractions in radiotherapy for malignant melanoma. AB - Eighty-nine cutaneous, subcutaneous or lymph node metastases of malignant melanoma in 15 patients were treated with radiotherapy using electron beams at appropriate energies (6-15 MeV). A total dose of 40 Gy was given in 8 fractions (fraction size 5 Gy) over 23 days. The therapy was given as two weekly fractions on two consecutive days with a 24-h interval. The next two fractions were given after a pause of 6 days. Eighty-six of 89 lesions (97%) responded to treatment, response rate being clearly dependent on tumour size. All the 67 lesions less than 2 cm in diameter responded, 51 of them (78%) completely disappearing, while in tumours over 4 cm among 10 lesions only 2 CR lesions were achieved. In cases where prolonged follow-up (greater than one year) was possible no major late side effects were observed. The treatment scheme with large fractions appears to be well-tolerated and effective for metastatic malignant melanoma. PMID- 1410574 TI - The clinical application of a non-axial treatment plan for pancreatic and biliary malignancies. AB - Standard radiation therapy for adenocarcinoma of the pancreas treats a substantial portion of the renal parenchyma. It was hypothesized that rotating the plane of treatment to a non-axial orientation, with the anterior field entering the patient from an inferior oblique direction, would decrease the renal dose of radiation without increasing the liver dose or compromising the target dose. To test this hypothesis, patients referred for radical radiation treatment for tumors of the pancreas or distal common bile duct were prospectively evaluated by performing treatment planning using axial and non-axial field arrangements. Treatment plans were compared using dose volume histograms (DVHs) of both kidneys and the liver. In all 15 cases analyzed, the non-axial plan was superior to the axial plan with respect to renal dose, without significantly increasing the hepatic dose and was used for treatment. Treatment was not significantly more complex nor was gastrointestinal toxicity increased. These findings show that non-axial field arrangements can be used on a routine basis to decrease the renal dose of radiation for the treatment of pancreatic and biliary malignancies. It is anticipated that in the future, a combination of DVH-guided treatment planning and sophisticated renal function studies will be necessary to permit a more accurate prediction of the probability of renal complications resulting from radiation therapy. PMID- 1410575 TI - The effect of the hypoxic cell drug SR-4233 alone or combined with the ionizing radiations on two human tumor cell lines having different radiosensitivity. AB - The influence of the hypoxic cell drug, SR-4233, alone and/or combined with ionizing radiations on the survival of two human cell lines having very different intrinsic radiosensitivity was analysed. The killing effect of SR-4233 in hypoxia was similar for both cell lines. Twenty microM SR-4233 under hypoxic conditions had a killing effect equivalent to 6.6 Gy for the poorly sensitive cell line (HT29) and equivalent to 3.9 Gy for the highly sensitive cell line (SW48). The effect of SR-4233 and ionizing radiations on these two cell lines was tested in vitro: the cells were incubated for one hour in hypoxia with or without 20 microM SR-4233 and then irradiated in air. The HT29 cells that survived treatment with SR-4233 are more radiosensitive than untreated cells. However, their radiosensitivity is similar to that of cells that have been given a dose of 6.6 Gy. This suggests that SR-4233 acts additively, rather than as a radiosensitiser. As SR-4233 acts selectively in hypoxia, these results appear encouraging for the treatment of poorly-radiosensitive human tumors. PMID- 1410576 TI - The effect of increasing the treatment time beyond three weeks on the control of T2 and T3 laryngeal cancer using radiotherapy. AB - Local control of cancer by radiotherapy may be prejudiced by accelerated tumour clonogen repopulation particularly during protracted treatment schedules. A series of 496 cases of T2 and T3 larynx cancer treated here by radiotherapy has been studied to examine the impact on local control of treatment durations ranging from 9 to 41 days. Data were analysed using a linear-quadratic formulation describing the fractionation sensitivity, with the incorporation of a parameter relating to treatment time. Using combined T2 and T3 data, the increase in dose required to maintain a constant local control (the time factor) was between 0.5 and 0.6 Gy per day. These values are similar to those reported for 4 weeks or more in the literature. Also, the calculated dose to control 50% of tumours, given over the standard Christie duration of 21 days, was on the line projected back from literature data over 28-66 days. The present data are consistent with the presence of such a time factor following a lag phase of not more than 3 weeks after starting radiotherapy. Hence, further consideration should be given to using shorter overall treatment times in radiotherapy for head and neck cancer. PMID- 1410577 TI - Aggressive treatment of intrathoracic recurrences of thymoma. AB - Between 1974 and 1988, 21 patients with intrathoracic recurrences of thymoma received radiotherapy with radical intent; surgery was always attempted when considered feasible: 11 patients were partially (6 cases) or totally (5 cases) resected before irradiation, while in the other 10 radiotherapy was the only treatment. In 7 cases the recurrence was confined to the anterior mediastinum, 9 had pleural nodules without mediastinal lesions and 5 had both mediastinal and pleural lesions. Mediastinal recurrences were treated by opposed parallel mediastinal fields with 2/3 of the dose delivered through the anterior port: doses ranged between 38 and 44 Gy; a boost of 10-16 Gy was given in patients not radically resected. Pleural nodules were treated with a variety of techniques according to the extent of the lesions. The 7-year survival of the whole group was 70%; 5 patients died: 4 with intrathoracic progression and one with distant metastases. The survival was 74% in the 11 patients having received surgery, either radical or subtotal, and 65% in the 10 patients treated with radiotherapy alone: the difference is not significant. Patients with Karnofsky index greater than 70 had a significantly better survival (100%, versus 28%, p = 0.0015). This is a selected series of patients presenting recurrences still amenable to a radical treatment either by surgery and radiotherapy or by radiotherapy alone: the results confirm that an aggressive approach is warranted in patients in good general conditions with recurrences confined to the mediastinum and/or 1 hemithorax. PMID- 1410578 TI - The use of asymmetric-field inversion gel electrophoresis to predict tumor cell radiosensitivity. AB - The success of a predictive assay for radiotherapy relies on the use of one or more tumor cell traits that equate with tumor radioresistance or radiosensitivity. These traits can be divided into intrinsic (genetic) and extrinsic (epi-genetic) factors. Most probably, a tumor's response to radiotherapy will be influenced by both of these sets of traits. Radiobiological analysis of cultured cells derived from explanted tumors of head and neck patients has shown that in vitro survival of tumor cells is not the only factor affecting tumor radiocurability. Two possible reasons are the high degree of selection involved in growing the cells in vitro and the inability to assess the contribution of the cell-cell contact effect with cultured cells. A possible means of overcoming both of these problems would be an assessment of the radiosensitivity of the cell population immediately after removal from the tumor. Since a good correlation exists between intrinsic cellular radioresistance and DNA double-strand break repair (DSBR) as assayed by the Neutral Elution technique [21], we have investigated the feasibility of using asymmetric field inversion gel electrophoresis (AFIGE) in identifying resistant tumor cells in vitro. AFIGE has several advantages over neutral elution in that it is faster (approximately 60-80 samples can be run on the same agarose gel) and, most importantly, one can visualize DNA damage and repair by staining the DNA with ethidium bromide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410579 TI - Potentiation of alkylating chemotherapy by dual function nitrofurans in multi cell spheroids and solid tumors. AB - The cytotoxicity and chemosensitizing potential of four dual function nitrofurans was determined in human HT-29 multi-cell spheroids and rodent KHT sarcoma solid tumors. Spheroids were treated with a range of doses of the bioreductive drugs for a period of up to 48 h and the extent of cell kill was assessed at various times after treatment. Cytotoxicity was determined using a clonogenic cell survival assay. The results demonstrated that two of the nitrofurans were even more toxic to spheroid cells than was the potent bioreductive nitroimidazole aziridine RSU 1069. The dose of the nitrofuran which, after a 24-h exposure, led to a survival value between 0.5 and 1.0, then was chosen for subsequent studies aimed at assessing the ability of these agents to potentiate the efficacy of the nitrosourea CCNU. Exposure to this chemotherapeutic agent was for a period of 1 h. The results indicated that all four dual function nitrofurans enhanced the cell killing of the conventional chemotherapeutic agent by factors ranging from 1.1 to 1.7. Subsequent studies evaluated the therapeutic benefit of combining these bioreductive agents and CCNU in KHT sarcoma-bearing C3H/HeJ mice. The nitrofurans were administered i.p. 0.5 h prior to the chemotherapy and tumor response was assessed by measuring the survival of clonogenic KHT cells 22-24 h after treatment. Normal tissue toxicity was determined using a bone marrow stem cell (CFU-GM) assay. Combining these bioreductive agents with CCNU increased the tumor cell kill by factors of 1.2 to 1.7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410580 TI - Radiosensitizing and repair-inhibiting properties of dipyridamole. AB - Radioresistance and postirradiation repair of potentially lethal damage (PLD repair) are important factors underlying failure to control local disease in cancer. Dipyridamole (DP) is known as a modifier of the action of cytotoxic drugs. We therefore investigated DP as a potential radiosensitizer and inhibitor of PLD repair in X-irradiated Chinese hamster ovary (CHO) cells in vitro. Exposure to the drug alone resulted in a slight reduction of the clonogenic capacity of the cells. Preincubation for 18 h with 10 and 20 microM DP in cells subcultured at low density, led to a significant radiosensitization. In confluent density-inhibited cultures, preincubation alone as well as pre- and postincubation with 20 microM DP resulted in a significant inhibition of PLD repair. Dipyridamole and related compounds may thus be useful tools for modifying and investigating the response of mammalian cells to radiation. PMID- 1410581 TI - A practical evaluation of five dose-volume histogram reduction algorithms. AB - A unifying approach to cumulative dose-volume histogram (CDVH) reduction analysis is presented, utilising two weighted linear interpolation models (VWD, DWV), two weighted probability models (VWP, DWP) and a novel integral probability model (IPM). As a test of their predictive value these algorithms were applied to CDVH data generated from lung doses, measured by TLD arrays in a female anthropomorphic phantom. Three arbitrary configurations of breast size and location of "target volume" within the breast were "treated", using an appropriate electron field (Varian Clinac 1800) or double-plane iridium-192 implant. Calculated effective doses from each of the reduction algorithms showed the iridium implant to be dosimetrically the most favourable in two the three configurations. Likewise, complication probabilities, based on a logistic dose volume response function showed lung complication probabilities to be lower for the interstitial technique in the same situations. All algorithms tested showed reasonable consistency, with the exception of the VWD. The rationale and value of comparative rather than absolute dose-volume histogram analyses are discussed. PMID- 1410582 TI - Maximizing setup accuracy using portal images as applied to a conformal boost technique for prostatic cancer. AB - A design procedure of a patient setup verification protocol based upon frequent digital acquisition of portal images is demonstrated with an application for conformal prostatic boost fields. The protocol aims at the elimination of large systematic deviations in the patient setup and includes decision rules which indicate when correction of the patient setup is needed. The decision rules were derived from the results of a theoretical and quantitative analysis of patient setup variations measured in three pelvic fields (one anterior-posterior and two lateral fields) of 105 fractions for nine patients. Deviations in the patient positioning, derived from one field, were quantified as two-dimensional (2-D) displacement vectors in the plane perpendicular to the beam axis by alignment of anatomical features in the portal and the simulator image. The magnitude of the overall setup variations along the anterior-posterior, superior-inferior and lateral directions varied between 2.6 and 3 mm (1 S.D.). Inter- and intra treatment variations could be separated, both having equal magnitudes of 1.7 to 2.2 mm (1 S.D.). In addition, intra-treatment variations appeared to be predictable which was a prerequisite for the development of the decision rules. The 2-D setup deviations, measured in the three fields of one fraction were strongly correlated and a 3-D displacement vector was calculated. Utilization of this 3-D vector in a setup verification protocol may lead to an early detection of systematic setup deviations. PMID- 1410583 TI - Primary radiotherapy of breast cancer: treatment results in locally advanced breast cancer and in operable patients selected by positive axillary apex biopsy. AB - To evaluate the efficacy of radiotherapy without surgery, treatment results in patients treated for locally advanced breast cancer (n = 209) and those selected by positive axillary apex biopsy (n = 289) in the period between 1977 and 1985 have been analysed retrospectively. Treatment consisted of primary irradiation to the breast and regional lymph nodes followed by a boost to the primary breast tumour and palpable regional disease to a mean normalised total dose (NTD) of 64.7 Gy with a range of 33.4-93 Gy (2 Gy fractions, alpha/beta = 5 Gy). Adjuvant systemic treatment was given in 30% of the locally advanced and in 40% of the apex positive patients. Thirty percent of the apex positive patients had an excisional biopsy of the breast tumour. By multivariate analysis a prognostic index is constructed for locoregional control, overall survival and distant disease-free interval. Primary tumour size and clinical nodal status are independent prognostic factors for locoregional control. Based on the prognostic index for local control four different groups can be identified with 5 year local control rates varying from 47 to 86%. Patients treated with adjuvant chemotherapy and patients irradiated to a NTD of 60 Gy or more had significantly better local control. For overall survival primary tumour size, clinical nodal size and age are independent prognostic factors. Patients irradiated to a NTD above 60 Gy had significantly better results. Survival according to the prognostic index for survival varies between 20 and 50% at 5 years for the four groups subdivided according to the index for survival. Primary tumour size, clinical node size and age are independent prognostic factors for distant disease-free interval. Patients treated with adjuvant hormonal therapy had significantly better results. In the four groups subdivided according to the prognostic index for distant disease-free interval results vary from 17 to 30% at 5 years. PMID- 1410584 TI - The influence of mineralising radionecrosis on the dose distribution in interstitial radiation therapy of brain tumours. AB - The influences of radionecroses arising during interstitial radiation of brain tumours with 125I, 192Ir or 198Au on dose distribution was investigated using Monte Carlo methods. The necroses have a higher density than normal tissue due to radiation-induced changes in tissue composition as well as mineral deposits. They can have a diameter of up to 1 cm around the single seeds. The higher density and changed chemical composition compared to homogeneous normal tissue leads to increased absorption of radiation around the necroses which results in a lower dose rate in the surrounding tissue. It is shown that the formation of necroses during treatment with higher energy radiation such as 192Ir (340 keV) or 198Au (400 keV) may be neglected during therapy planning as the dose rate is affected by less than 2%. If low energy radiation, e.g. 125I (28 keV) is used, the dose rate can be reduced by more than 30%. In this case the influence of the necroses on dose distribution, at least for permanent 125I implantation, may not be negligible. PMID- 1410585 TI - Cardiac doses in post-operative breast irradiation. AB - Data were collected on radiation doses given to the heart and coronary arteries during primary breast irradiation in order to analyze factors which might be important in the aetiology of subsequent cardiac-related disease. Twenty eight patients with breast cancer were studied. Fourteen patients treated from 1957 to 1984 were studied retrospectively (group 1), and 14 treated from 1988 to 1989 were studied prospectively (group 2). All patients had stage I or II disease at presentation, and were under 70 years of age. None had chemotherapy as a primary form of treatment. Patients were given a computed tomography scan of the chest, and three-dimensional reconstruction was made of the heart, lung and body contour. Original dose distributions were super-imposed on these outlines, and doses to the total cardiac volume and three main coronary arteries were estimated using an alpha/beta ratio of 4 Gy. Nine out of 14 patients in group 1 had a mastectomy followed mainly by orthovoltage radiation with similar techniques used up until 1984. Thirteen out of 14 patients in group 2 had conservative surgery followed by a modern two- or four-field megavoltage technique. We found that for patients with left-sided tumours (n = 20), the heart volume irradiated to a minimum extrapolated target dose of 5 Gy is significantly decreased for patients treated with a modern technique (group 2) when compared with those treated with earlier techniques (group 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410587 TI - Hypothyroidism following radiotherapy for head and neck cancer: multivariate analysis of risk factors. AB - The incidence of hypothyroidism following radiotherapy for head and neck cancer is 10-45% in several series. In order to identify possible risk factors a multivariate analysis was performed in 221 patients previously treated with either radiotherapy alone or combined with surgery or chemotherapy. Diagnostic procedures included: total T3 and T4, free T4 and TSH measured by radioimmunoassay, and thyroid scintigraphy. The absolute rate of hypothyroidism was 41.17% (subclinical 26.24%, clinical 14.93%). No thyroid nodules were detected in any patient. By multivariate analysis, risk factors that significantly influenced a higher incidence of hypofunction were: high radiation dose (p = 0.000), combination of radiotherapy and cervical surgery (p = 0.003), time from therapy (p = 0.022) and no shielding of midline (p = 0.026). PMID- 1410586 TI - Vestibular apparatus disorders after external radiation therapy for head and neck cancers. AB - External irradiation of different head and neck cancers may involve parts of the ear. The vestibular function of 25 patients in which the inner ear was comprised in the irradiated volume was investigated by electronystagmography (ENG). Doses administered to the vestibular system ranged between 2800 and 5120 cGy. Five patients suffered subjective vertigo or dizziness. Eleven patients (three out of five with vertigo) showed vestibular abnormalities to ENG (44% of the total). Altered responses to specific tests were as follow: six patients to the bithermal caloric stimulation, two to the pendular-sinusoidal test and the other three to both of them. Patients were evaluated 3 and 6 months after the ending of the radiation therapy course. At the first evaluation, abnormalities to caloric test were noted in three patients (12%) and to sinusoidal rotatory test in one patient (4%). At the second evaluation, rates of abnormal response increased to 36% and 20%, respectively. Vestibular disorders seemed to be scantly related to the total radiation dose. Data of literature are discussed in order to identify possible implications on treatment planning. PMID- 1410588 TI - Pharmacokinetics of nicotinamide and its effect on blood pressure, pulse and body temperature in normal human volunteers. AB - The pharmacokinetics of nicotinamide were studied in four human volunteers after oral doses of 1-6 g. Plasma concentrations and clearance rates of the vitamin were found to be dose-dependent, with a half-life of approximately 7-9 h for the two highest doses administered (4 and 6 g), approximately 4 h with 2 g and approximately 1.5 h with a 1-g dose. Peak concentrations ranged from 0.7 to 1.1 mumol.ml-1 after a 6-g dose. The time to reach peak plasma concentration was dose independent with a broad range from 0.73 to 3 h. In this study, nicotinamide had no detectable effect on blood pressure, pulse or body temperature. PMID- 1410589 TI - BW12C-induced changes in haemoglobin-oxygen affinity in mice and its influence on the radiation response of a C3H mouse mammary carcinoma. AB - The effect of the substituted benzaldehyde BW12C on haemoglobin-oxygen binding affinity, tumour radiation response and blood perfusion were investigated in a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Mouse P50 (partial pressure of oxygen at half saturation) was estimated using an ABL blood gas analyzer; radiation response determined from tumour regrowth and local tumour control assays; and tumour blood perfusion measured with a 86RbCl extraction procedure. A single intravenous injection of BW12C substantially decreased mouse P50. This effect was dependent on the time after injection with the nadir observed within 15 min and only returning to normal after several hours. It was also dependent on drug dose, the decrease becoming larger with increasing concentration, reaching a maximum 50% reduction at 70 mg/kg. The decrease in P50 could be maintained for at least 6 h following injection of 70 mg/kg, if mice were also given 25 mg/kg at hourly intervals. However, no changes in radiation response or tumour blood perfusion were observed with either single or multiple administrations of BW12C. These results suggest that BW12C induced changes in tumour hypoxia reported by several groups of workers, may not be entirely the result of a change in haemoglobin-oxygen affinity. PMID- 1410590 TI - A pilot study of a method of estimating the number of functional eccrine sweat glands in irradiated human skin. AB - Following stimulation with pilocarpine, the secretion from eccrine sweat glands produces characteristic imprints in hardening silicone polymers applied to the skin. This permits an accurate determination of the numerical density of functional eccrine glands in irradiated skin which can be compared to non irradiated skin. A description of this inexpensive, noninvasive, and quantitative technique is presented as well as preliminary results determined in six normal subjects and 28 irradiated patients. Eleven patients, with atrophy and telangiectasia after radiotherapy to the skin to a high dose, were found to have no functional eccrine glands by this technique. A range of results from normal numbers of eccrine glands through partial and, rarely, complete loss was observed in patients given lower doses and in whom the skin was visually normal. When the irradiated side outside the boost area in 16 breast cancer patients who received postoperative radiotherapy was compared to an equivalent area on the untreated, contralateral side, 11 showed a greater than 50% reduction in the density of functional eccrine glands. The method appears to be a sensitive, quantitative assay for a permanent change in skin and so ought to facilitate meaningful comparison of different regimens of radiotherapy. Further studies are required to determine the dose-response relationship, latency and progression of the observed changes. PMID- 1410591 TI - Radiotherapy treatment planning of basal meningiomas: improved tumor localization by correlation of CT and MR imaging data. AB - A localization technique, based on three-dimensional CT and MR imaging data for precision radiotherapy of basal meningiomas, is presented. Indications for radiotherapy included unresected tumors, gross disease remaining despite surgery, and recurrences. The patient's head was fixed in a stereotactic localization system which is usable at the CT, MR and the linear accelerator installations. The geometrical distortion of MR imaging data was evaluated in three dimensions by phantom measurements. The geometrical distortion was "corrected" (reducing displacements to the size of a pixel) by calculations based on modelling the distortion as a fourth order two-dimensional polynomial. The target volume was defined in three-dimensional MR imaging data after application of 0.1 mmol/kg b.w. Gd-DTPA solution and transferred precisely from MR onto CT data to provide a map of the radiation attenuation coefficient for dose calculation. The superior soft tissue contrast of MR showed an excellent tumor delineation especially when the bony base of the skull obscured the target in CT images. Target volume, calculated dose distribution, and critical structures could be transferred between CT and MR imaging data and displayed as three-dimensional shaded structures for better assessment for matching of target volume and dose distribution. With the described planning system a more precise target definition of basal meningiomas was possible by integration of the superior tumor delineation in MR compared with CT. PMID- 1410592 TI - "PCL" a new automatic fast reader suitable for in vivo dosimetry. AB - The authors present a new automatic TLD reader specially designed for medical dosimetric applications, which allow considerable time-saving. The "PCL" reader is based on an isothermal heating kinetics and can be used with TL material of any nature and any shape (powder, microrods, pellets). Doses from 1 microGy to 10 Gy can be measured, or higher doses by interposing an optical absorber in front of the PM. The readout system is controlled by an IBM compatible personal computer. Results can be printed under the form defined by the users and then can be straightly stored in a patient sheet or an experience book. Tests performed with LiF chips TLD 100 and 700 (HARSHAW), Li2B4O7:Mn discs LiB (ALNOR), LiF powder PTL 717 (DESMARQUET) and Li2B4O7:Cu powder (CEN-FAR) are presented. They show a good reproducibility and interesting dosimetric properties. PMID- 1410593 TI - Are port films reliable for in vivo exit dose measurements? AB - The possibility of using conventional port films as an in vivo method for obtaining relative exit dose distribution in patients is evaluated. Kodak "Verification" films in "Localization" cassettes are positioned in the usual clinical conditions behind an homogeneous polystyrene phantom as well as behind a phantom containing air, wood and aluminium inhomogeneities. Taking beam divergency into account the densitometric profiles are projected back to the exit side of the phantom. They are compared to the profiles obtained with an ionization chamber used under full backscatter conditions. The agreement between the off-axis ratios determined with either method are mostly better than 2% and never exceed 5%. These phantom measurements are completed by a comparison between off-axis ratios determined on a port film for a head and neck patient and those obtained by diode dosimetry applied on the patient at the exit side of the beam. A similar agreement as between film and ion chamber on the phantoms is obtained. These encouraging results illustrate the possibilities of using conventional port films for in vivo dosimetry. PMID- 1410595 TI - Are you prepared? PMID- 1410594 TI - The treatment of resistant neuroblastoma with 131I-mIBG: alternative methods of dose prescription. AB - A UK multi-centre study has been carried out to collect medical and dosimetry data from treatments with 131I-metaiodobenzylguanidine (mIBG) for patients suffering from resistant neuroblastoma. All data have been acquired in a standardised way, following strict physics and clinical protocols. The accuracy of three different methods of dose prescription was studied. The results show that the most accurate method involved the use of an initial tracer study to determine the therapeutic activity required to deliver a predetermined absorbed whole-body (WB) dose. PMID- 1410597 TI - Home study. PMID- 1410596 TI - Case #1. Developmental lingual mandibular salivary gland defect. PMID- 1410598 TI - Perio charting systems. PMID- 1410599 TI - Organization provides timely information on infection control. PMID- 1410600 TI - Case #1. Distomolar. PMID- 1410601 TI - Of special concern. PMID- 1410602 TI - Kids' oral health program rewarding for New York RDH. PMID- 1410603 TI - Helping those in need. PMID- 1410604 TI - OSHA issues the final protection standards on bloodborne pathogens. PMID- 1410605 TI - Patients undergoing chemotherapy have special treatment needs. PMID- 1410606 TI - A new curet series: the Gracey curvettes. PMID- 1410607 TI - A reminder about the benefits of dental fluorides. PMID- 1410608 TI - Case #3. Dens in dente. PMID- 1410609 TI - It's time to let go of our unconditional loyalty to floss. PMID- 1410610 TI - Taking a walk on the wild side. PMID- 1410611 TI - Salary and benefits review. PMID- 1410612 TI - A dental picture is worth a thousand words. PMID- 1410613 TI - Are we missing an important segment of the population? PMID- 1410614 TI - OSHA exposure control plan requires organized records. PMID- 1410615 TI - Case #4. Ranula. PMID- 1410617 TI - Silent victims. PMID- 1410616 TI - Ugh! What can we do about that awful morning mouth? PMID- 1410618 TI - Ultrasonics come of age. PMID- 1410619 TI - Getting to the heart of the matter. PMID- 1410620 TI - OSHA standard requires some control of staffs' activities. PMID- 1410621 TI - The right STEPS will help guide anxious patients through treatment. PMID- 1410622 TI - Frequent flosser program is RDH's creative way to motivate patients. PMID- 1410623 TI - Our education builds hygiene's future for the 21st century. PMID- 1410624 TI - The entrepreneurial spirit. PMID- 1410625 TI - Case #5. Angular cheilitis. PMID- 1410626 TI - Knowing mechanical differences helps distinguish ultrasonic units. PMID- 1410627 TI - Employers required to supply workers with protective gear. PMID- 1410628 TI - Protect your paycheck. PMID- 1410629 TI - Perio program can put money where the mouth is. PMID- 1410630 TI - Case #6. Tetracycline staining. PMID- 1410631 TI - Effective sonic and ultrasonic use is all in the technique. PMID- 1410632 TI - Remember, eye protection is necessary for patients too. PMID- 1410633 TI - OSHA says hepatitis B vaccine must be offered free to workers. PMID- 1410634 TI - Dental health education: is it an option for you? PMID- 1410635 TI - Spirit of volunteerism abounds at Indiana dental health clinic. PMID- 1410636 TI - Getting patients to take ownership of their oral health improves recalls. PMID- 1410637 TI - Sign for the times. PMID- 1410638 TI - Case #7. Lateral periodontal cyst. PMID- 1410640 TI - Gold medal treatment. PMID- 1410639 TI - What to do if employee reports exposure to bloodborne disease. PMID- 1410641 TI - Fear of AIDS. PMID- 1410642 TI - Studies question extensive root planing to remove cementum. PMID- 1410643 TI - Hygienists in Israel want to work more hours per week. PMID- 1410644 TI - Meticulous attention to infection control reassures wary patients. PMID- 1410645 TI - Working for VA medical centers offers RDHs numerous benefits. PMID- 1410646 TI - Advances in diagnostic imaging of interstitial lung disease. PMID- 1410647 TI - Clinical assessment of interstitial lung diseases. PMID- 1410648 TI - Conventional radiology and high resolution computed tomography of lung anatomy and general semeiotics. PMID- 1410649 TI - Diagnostic imaging of non infiltrative interstitial lung disease. PMID- 1410650 TI - Diagnostic imaging of pneumoconioses. PMID- 1410651 TI - Nuclear medicine: what role in interstitial lung disease? PMID- 1410652 TI - Glycidyloxy compounds used in epoxy resin systems: a toxicology review. AB - The glycidyloxy compounds constitute an important group of chemicals used extensively in the formulation of epoxy resin systems employed in coatings, electronics, structural composites, and adhesives. Although extensive toxicological data are available on glycidyloxy compounds, use and understanding of the data have been hampered by two major problems: (1) proper identification and complexity of the epoxy systems in question, and (2) absence of meaningful classification of epoxy materials. This paper provides a classification scheme with CAS numbers and reviews the mammalian toxicology of the most common glycidyloxy derivatives used in epoxy resin systems based on both published and proprietary information. Although the toxicity of many of the glycidyloxy compounds used in epoxy resin systems can be characterized as low, the diversity of compounds found within this group precludes broad generalizations for the class. This comprehensive account should facilitate a clearer understanding of the potential health effects and allow for easier comparison among compounds containing the glycidyloxy moiety. PMID- 1410653 TI - Cancer risk assessment: the science that is not. AB - Regulators have adopted the assumption of low dose linearity in cancer risk assessment, variously justified as scientifically correct and as responsible public health policy. Corollary assumptions are the one-molecule-one-hit hypothesis, the exclusion of no-effect thresholds, and the equivalency of response in experimental rodents and man. While our understanding of the carcinogenesis process remains tentative, these generalizations are not sustained by the limited scientific evidence available, not even as interim working hypotheses. In this light, they reflect a facile bureaucratic response to pragmatic demands borne of political perceptions, rather than the recognition of a complex and still opaque reality. PMID- 1410654 TI - Relationship between the shape of dose-response curves and background tumor rates. AB - Various authors have argued that a chemical which augments a carcinogenic process, which is already producing tumors spontaneously, will produce an increase in tumors no matter how small the dose. For this situation, no threshold dose exists whether or not the chemical is genotoxic. Under such conditions, it is expected that the dose-response will contain a linear term. A large database of animal bioassays (Gold et al., 1984) was examined to study the relationship between the shape of dose-response curves and the background tumor rate. The multistage model was fit to 143 data sets from 75 different chemicals. As expected, the presence of the linear term was correlated with the background tumor rate and the presence of higher degree terms in dose (cubic or greater) decreased as the background rate increased. This examination of a large number of chronic bioassay results appears to support the premise that low dose linearity is generally expected for tumor sites where background tumors occur, even for carcinogens which were negative by the Salmonella genotoxicity test. PMID- 1410655 TI - A proposed approach to regulating contaminated soil: identify safe concentrations for seven of the most frequently encountered exposure scenarios. AB - Since 1980, more than 10,000 sites in the United States have been shown to contain soil which has elevated concentrations of various xenobiotics. Since that time, guidelines for deciding whether the level of contamination is worthy of concern have been proposed or promulgated by dozens of local, state, and federal regulatory agencies. Unfortunately, there has been little consistency in the guidelines suggested for each soil contaminant. For example, (a) the basis or rationale for some of the cleanup levels is unclear, (b) approaches to setting cleanup levels vary between states and agencies, (c) cleanup objectives often vary among agencies within the same state, and (d) the cleanup levels are usually set in a scientifically haphazard manner. This paper proposes that the most cost effective and efficient way to quickly regulate contaminated soil is to establish "safe" concentrations for each chemical for the seven most common exposure scenarios. These exposure scenarios include (1) residential, (2) industrial, (3) agricultural, (4) recreational, (5) groundwater, (6) wildlife and aquatic species, and (7) runoff/erosion of particulates to waterways. The scientific approach and rationale for calculating the cleanup criteria are illustrated by evaluating dioxin and benzene, toluene, and xylene (BTX). The methods suggested here indicate that levels of dioxin of 25 and 50 ppb in residential and industrial soils, respectively, should be acceptable. The predominant concern for the agricultural and recreational scenarios is the runoff of particulates to waterways. For BTX, benzene will dictate the degree of cleanup and the primary hazard at most residential sites will be the inhalation of vapors. Benzene concentrations of 2.5, 14, and 250 ppm should be acceptable for residential, industrial, and recreational soils, respectively. Depending on the depth to groundwater and aquifer use, protection of groundwater may be the driving concern for establishing BTX cleanup levels and must be determined using site-specific factors. PMID- 1410656 TI - On the carcinogenicity of cadmium by the oral route. AB - Cadmium and cadmium compounds are carcinogenic both by inhalation and by injection. For purposes of risk assessment, a prudent public health approach has been that, if a chemical has been demonstrated to be carcinogenic by one route, it should be considered carcinogenic by all routes. This policy has been questioned for several toxic metals including cadmium. After reviewing the literature on cadmium carcinogenicity and genotoxicity, we think that cadmium should be considered noncarcinogenic by the oral route. The bases for this decision included: (1) a database for genotoxicity of cadmium with more negative test results than positive results and with most positive results in in vitro tests, indicating that cadmium has limited genotoxicity; (2) some epidemiologic evidence of respiratory tract cancer and prostatic cancer in people occupationally exposed to airborne cadmium but no reliable evidence of gastrointestinal tract cancers in workers; and (3) a large dietary oncogenicity study in rats of cadmium chloride at several dose levels, including a maximally tolerated dose (50 ppm) in males, which showed no increase of tumors due to cadmium ingestion in all of the 19 tissues examined. The conclusion that an agent, which has been shown to be carcinogenic by one route of exposure, is not carcinogenic by a second route should be made only in the presence of robust data which indicate the lack of effect via the second route of exposure. PMID- 1410657 TI - An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals. AB - A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals. PMID- 1410658 TI - Rising cancer mortality in the United States, 1962-1987: evidence against environmental causation. AB - The recorded rise in cancer mortality, particularly in industrialized nations such as the United States, is often attributed to increasing environmental carcinogens and has resulted in the public expectation for increased regulation. However, longitudinal Gompertzian analysis indicates that the major factor for rising cancer mortality is the increasing deterministic competitiveness of cancer in a climate that is becoming more conducive to human survival. Hence, rising cancer mortality is a predictable manifestation of a natural relationship between human aging and mortality, and should not be interpreted as evidence of increased environmental carcinogens. PMID- 1410659 TI - Exposure to airborne asbestos in buildings. AB - The concentration of airborne asbestos in buildings and its implication for the health of building occupants is a major public health issue. A total of 2892 air samples from 315 public, commercial, residential, school, and university buildings has been analyzed by transmission electron microscopy. The buildings that were surveyed were the subject of litigation related to suits alleging the general building occupants were exposed to a potential health hazard as a result of exposure to the presence of asbestos containing materials (ACM). The average concentration of all asbestos structures was 0.02 structures/ml (s/ml) and the average concentration of asbestos greater than or equal to 5 microns long was 0.00013 fibers/ml (f/ml). The concentration of asbestos was higher in schools than in other buildings. In 48% of indoor samples and 75% of outdoor samples, no asbestos fibers were detected. The observed airborne concentration in 74% of the indoor samples and 96% of the outdoor samples is below the Asbestos Hazard Emergency Response Act clearance level of 0.01 s/ml. Finally, using those fibers which could be seen optically, all indoor samples and all outdoor samples are below the Occupational Safety and Health Administration permissible exposure level of 0.1 f/ml for fibers greater than or equal to 5 microns in length. These results provide substantive verification of the findings of the U.S. Environmental Protection Agency public building study which found very low ambient concentrations of asbestos fibers in buildings with ACM, irrespective of the condition of the material in the buildings. PMID- 1410660 TI - [Synchrotron radiation: a new source in x-ray mammography]. AB - This work was aimed at evaluating the image quality obtainable in X-ray mammography using synchrotron radiation monochromatic lines. After a short review of the current mammographic techniques, the main features of synchroton radiation in the X-ray field are analyzed, especially of that emitted by the Adone storage ring. Its features are then compared with the radiation emitted by a Coolidge tube. The experimental unit used in this study, including beamline, monochromator and mammograph, is then described together with the experimental method for carrying out a series of experiments in the mammographic field employing both monochromatic lines (E = 17 keV) and white radiation from conventional sources. The first series of experiments is described, which employed standard phantoms: the dependence of resolution and contrast on both wavelength and thickness of breast specimens is reported. Several mammograms of neoplastic breast specimens were obtained after mastectomy: they were acquired using both synchrotron monochromatic lines and radiation emitted by a conventional tube and employing the same acquisition system. The comparison of the two series of images shows that synchrotron radiation can demonstrate a high number of anatomopathologic details with high definition, contrast and resolution which cannot be obtained by means of a conventional source. Our results appear very promising and suggest synchrotron radiation as the major tool in the early diagnosis of neoplastic breast lesions. PMID- 1410661 TI - [Image perception and interpretation in senology. The relationship between the clinical picture, radiological sign and histology]. AB - Once more, the authors are confronted with the difficult interpretation of senological images. When reviewing the radiologic features of a series including the symptomatic, the asymptomatic and the male breasts, the goal is to relate the patterns to clinical and histologic findings in order to improve the perception of the radiologist himself in transferring and integrating the information. The final conclusions, after reviewing the images, are: a) for the correct interpretation of senological images, the sign must be correlated with clinical findings and with data from other modalities; b) the radiologist's attitude must be always investigative and never exhaustive, due to the variability of all factors, which sometimes make a judgement of "radiological tranquility" in the breast impossible; c) the radiologist must, nowadays, improve his perception of senological images, thus becoming the one who knows how to correlate clinics to the images. By increasing his perception, his interpretation capabilities will certainly increase too. PMID- 1410662 TI - [A multicenter study for the evaluation of the diagnostic efficiency of mammography and echography in nonpalpable breast neoplasms]. AB - The Breast Section of the Italian Society of Radiology set up a cooperative study which included 17 Departments of Radiology and Breast Diagnosis in order to evaluate the diagnostic accuracy of US versus mammography in nonpalpable breast lesions. From January 1, 1989 to december 31, 1990, 400 nonpalpable breast lesions (142 benign lesions, 59 in situ and 199 infiltrating carcinomas) were detected by mammography and/or US; they had questionable/suspicious findings which called for further investigation by means of cytology and/or histology. US proved much less sensitive in non-palpable carcinomas than mammography (49.2% vs 93.8%), also in younger women, and failed to detect 50% of the benign/malignant nonpalpable lesions identified by mammography. US sensitivity was directly related to lesion diameter and probe frequency: 38.7% in infiltrating carcinomas < or = 5 mm vs 56.8% in those > 10 mm; 12% in the patients examined with a 5-MHz probe vs 57.7% in those examined with a > or = 7.5-MHz probe. Furthermore, the most significant US patterns of nonpalpable lesion were irregular contours, posterior attenuation and irregular internal echoes, while an irregular skin line and Cooper ligaments had no significant relation with carcinoma. Thus, breast US cannot be used as a screening test on asymptomatic patients not even on young women with radiologically dense breasts. On the contrary, US performed with high frequency probes is useful in the assessment of nonpalpable lesions identified by mammography, and allows, in many cases, US-guided cytology and preoperative localization. PMID- 1410663 TI - [The diagnostic imaging of complex breast nodules]. AB - This study was aimed at determining the role of high-frequency (7.5 MHz) US combined with cytology in the diagnosis of complex breast nodules (complex cysts- cystic tumors). The study population included 60 patients presenting with complex breast nodules selected on the basis of US patterns among 3,000 cases. All patients were also submitted to US-guided fine-needle aspiration biopsy (FNAB). Cytology of nipple discharge was always performed when discharge was present (15 cases), mammography was performed in 50 cases and pneumocystography in 10. US allowed the identification of the lesion in all patients and the diagnosis of nature in 73%; with FNAB the figure reached 96.7%. Mammography identified the lesion in 95% of patients, but failed to reveal the complex nature of the nodule. In a small number of cases mammography proved to be a useful complementary tool demonstrating malignant features not recognizable on US images. On the contrary, pneumocystography yielded no further information with respect to US. Diagnostic control was obtained by means of surgery in 30 patients and of clinical-US follow up in the extant 30 cases. On the basis of their US features the lesions were classified into two groups: I) nodules having a mainly liquid component--i.e., hemorrhagic, septic, multilocular cysts, papillary cystadenoma; II) nodules having a mainly solid component--i.e., solitary intraductal papilloma, intracystic carcinoma, mixed carcinoma, phylloid adenoma, sarcoma. As to the former group, US proved reliable in making a diagnosis in the cases with typical hemorrhagic, septic and multilocular cysts. In the atypical cases, FNAB of the solid component of the nodule was necessary to differentiate irregular clots, thick septa or inflammatory thickening from different conditions. As to the latter group, FNAB of the solid component and/or mammography proved useful in making a diagnosis, even though to this aim US revealed peculiar patterns which were highly suggestive. In our experience, combined US and FNAB are of basic importance in the diagnosis of breast lesions, thus replacing pneumocystography which has been widely employed so far. As regards mammography, its role seems limited to pointing out the peculiar characters of malignancy which could not be demonstrated otherwise. PMID- 1410664 TI - [A comparison between echography and computed tomography in assessing neoplastic recurrences in superficial soft tissues]. AB - Thirty-seven superficial soft-tissue recurrences were evaluated with ultrasonography (US) and computed tomography (CT) to assess the correct diagnostic approach. US and CT examinations were performed at the same time. High frequency US probes and a third-generation CT scanner were employed; all the lesions underwent also histology or cytology. US correctly identified as recurrences or fibrous tissue all the 37 lesions, whereas CT diagnosed 30 lesions only. Seven of the 14 recurrences < 2 cm diameter were not demonstrated. In conclusion, US provides more reliable information than CT relative to small lesions, which suggests that US must be performed just after therapy. Nevertheless, when bone involvement is suspected, CT is required and its use is also suggested to monitor distant metastases. PMID- 1410665 TI - [Contrast media in echography]. AB - In medical US, the use of specific contrast media to increase the echogenicity of structures and organs changes their absorption of the US beam, and modifies the through-transmission velocity. This can be of great diagnostic value. Contrast media can help depict vessels and cavities, increase the sensitivity of Doppler examination, and make the differentiation of normal and pathologic tissues easier. The products which are currently available do not completely fulfill the needs of clinical researchers. The first papers reporting on some clinical applications of these contrast media in humans are now appearing in literature. Contrast media for diagnostic US can be classified in five groups: 1) free gas bubbles; 2) stabilized gas bubbles; 3) colloidal suspensions; 4) emulsions; 5) aqueous solutions. These agents are quite different, as to both chemical and physical features and distribution within living tissues. Different clinical applications are thus possible for each of them; a unique contrast medium which will meet all the needs of the various clinical situations seems inconceivable at present. Most probably, a variety of products will develop, each with its own application field; in clinical practice, it seems likely that different products will be used, according to the specific clinical needs. PMID- 1410666 TI - [Digital radiology with storage phosphors in cephalometric study in orthodontics]. AB - Conventional radiology is continually modified with the development of digital systems which can be used for several types of radiologic examinations. Our study was aimed at evaluating the advantages of these new technologies in the orthodontic field, where the problems associated with image quality and radiation protection are major especially in young patients; the latter goal is achievable by dramatically reducing radiation dose and by avoiding repeating the exam. In our study, we compared lateral teleradiographs of the skull for cephalometric analysis obtained using conventional and digital diagnostic methods. The preliminary results demonstrated that the two imaging techniques did not differ relative to bone structure representation, even though the digital system provided better visualization of soft tissue structures. Computed radiography also allowed a marked reduction in the number of repeats and reduced radiation dose. The current disadvantages of this imaging method are the high initial cost of the equipment, reduced work rate, and the need of frequent technical assistance. PMID- 1410667 TI - [Destructive spondylopathy in the dialysis patient. The diagnostic role of magnetic resonance]. AB - Magnetic resonance imaging (MRI) was employed to study 7 long-term hemodialysis patients affected with destructive amyloid spondyloarthropathy. In the appropriate clinical setting, MRI proved to be more useful than conventional radiography or CT and more definitive in excluding infections. Indeed, MRI can replace more invasive procedures in making the correct diagnosis. Different than what is reported in literature, a high incidence of odontoid lesions (C2) was observed in our series, with extraosseous and extradural deposits of soft tissue masses (amyloid pseudotumors), subluxation, odontoid invagination and medullary compression. Bone lesions, involved disks and amyloid pseudotumors typically exhibited low-intensity signal on both T1- and T2-weighted sequences and no enhancement following Gd-DTPA injection. The use of MRI is thus suggested, especially at cervical level, also in case of relatively mild symptoms. PMID- 1410668 TI - [Psoriasis arthropathica. A review of the literature, general considerations and the authors' personal experience]. AB - A retrospective study has been carried out on 897 psoriatic patients in order to verify the incidence and radiological patterns of psoriatic arthropathy (PA). Site of involved joints, appearance and degree of involvement were correlated with extent of skin disease and blood test results. Sixty-five patients (7%) showed "clinical" arthritis whereas only 20 cases (2.2%) were radiologically positive; among them, 35% were classified as "severe" forms. Peripheral arthritis was observed in all cases, involving the hand in 85% of patients. The distal interphalangeal joints were the most affected location in the feet (78%) and the proximal interphalangeal joints in the hands (94%). The extant small peripheral joints were involved in decreasing rates proceeding proximally. Bilateral and asymmetric involvement was observed in most of the patients; hypertrophic interphalangeal joints erosion was the typical pattern in 100% of cases, evolving in rheumatoid-like ankylosis in 23% of them. Spondylitis and/or sacroiliitis were associated in 50% of patients. No correlation between degree of arthritis and skin disease was found in our series, with the exception of proximal and axial joints arthritis, in which extensive skin disease and severe small joints involvement were associated in 80% of cases. Clear differential features were demonstrated between peripheral PA and rheumatoid arthritis, and between spinal involvement in PA and ankylosing spondylitis. Poor correlation of distal arthritis to psoriatic nail involvement was also demonstrated. PMID- 1410669 TI - [The treatment of acute cholecystitis by percutaneous cholecystostomy]. AB - The authors report on their personal experience with percutaneous cholecystostomy (PC) in 36 cases of acute cholecystitis (AC). PC was successful in 34 cases, improving the clinical condition of the patients within the first hour following treatment and normalizing the laboratory data within 24-48 hours. Twenty-seven patients with calculous AC underwent cholecystectomy within 4-15 days. In 6 cases (3 calculous and 3 acalculous ACs) PC was the only treatment performed; in one case (calculous AC) PC was combined with lithotomy, the stone fragments being extracted via the cholecystostomy. According to literature reports, to date PC has been performed mainly--as an alternative to surgical cholecystostomy--on the patients unsuitable for cholecystectomy due to their age or to severe impairment of their conditions. In our experience, the procedure can be performed on a wider range of patients as a final (notably in acalculous AC) or temporary step (notably in calculous AC where it may allow cholecystectomy to be delayed and thus performed under better clinical conditions, with decreased morbidity and mortality risks). PMID- 1410670 TI - [Biliodigestive anastomoses on echography. The normal and pathological aspects]. AB - The normal and pathological US features of different types of bilioenterostomy (hepaticojejunostomy, choledochoduodenostomy, polyductal bilioenteric anastomosis) are described, as observed in a prospective study of 27 patients, for a total number of 35 (18 normal and 17 abnormal) examinations. For 20 patients with hepaticojejunostomy, the bilioenteric anastomosis was identified on 13/13 normal examinations and 10/12 pathological examinations. For 2 patients with choledochoduodenostomy, the bilioenteric anastomosis was identified on 2/2 examinations. For 5 patients with polyductal bilioenteric anastomosis (each patient having 2 or 3 anastomoses), all surgical anastomoses were separately identified on 6/8 examinations; as for the remaining 2 patients, 2/3 and 1/3 anastomoses were seen. An abnormal condition was correctly recognized in all the 11 patients with local disease (lithiasis and benign biliary stricture, 2 patients; benign biliary stricture, 5 patients; primary cholangiocarcinoma, 1 patient; recurrent malignancy, 3 patients); in 1 patient, parenchymal and biliary abnormalities due to vascular obstruction were misinterpreted as a result of benign stricture. US can demonstrate the surgical anastomoses between the resected common bile duct or second order intrahepatic ducts and the jejunal loop, with typical features according to the type of surgery performed. Knowledge of such normal appearances after bilioenteric surgery is mandatory in order to detect and correctly evaluate such possible abnormalities at this site as lithiasis and benign or malignant strictures. PMID- 1410671 TI - [The experience of diagnostic and therapeutic integration in rectal cancer. Preliminary notes]. AB - In our University, many different radiosurgical options are available to treat rectal carcinoma. Selecting the patients to submit to treatment requires accurate clinical and radiological staging. A team of radiologists, radiotherapists, surgeons, endoscopists and pathologists has been created to stage the patients and to follow the final results. The team have decided the diagnostic and therapeutic protocols. The patients with rectal cancer undergo radiotherapy after staging and are subsequently restaged. If indicated, surgery is performed and histology is compared with restaging, to assess the accuracy of the diagnostic procedures. All diagnostic and therapeutic decisions are made collectively by the team, during scheduled meetings. All data are stored in a computer program. This paper deals with the working method we used, its advantages and the outcome of the first 23 studied patients. Restaging was compared with histology: transrectal US (performed in 8 patients) showed 100% accuracy in evaluating local tumor spread (T). CT had 91% accuracy in defining T and 60% accuracy in N, with a tendency to overstaging. In 78% of patients > 50% reduction of tumor size was observed and the distance from the anal canal increased in 95.5%. This study will provide the overall accuracy of the clinico-radiologic staging, the survival rates and the indication of prognostic signs. PMID- 1410672 TI - [The anatomical assessment of the renal fascia in the normal subject by using computed tomographic equipment with advanced technology]. AB - One hundred patients, affected with diseases not involving the peri-renal and pararenal spaces, have been examined in order to evaluate the visibility of the renal fasciae, using a CT scanner provided with high spatial and contrast resolution. The anterior renal fascia has been recognized in 71% of cases on the right side and in 88% on the left. The posterior renal fascia had 96% of positive bilateral detectability. The latero-conal fascia was detected in 83% of cases on the right and in 91% on the left. The inter-renal fascia was recognized in 25% of cases, at the pancreas or, more frequently, on caudal planes. The peri-renal septa were seen in 58% of cases, mainly on the left side. Compared to previous data reported by other authors, the visibility of the renal fasciae has been increased by the greater spatial and contrast resolution offered by the new CT scanner, thus allowing better anatomical evaluation of peri and para-renal spaces. PMID- 1410673 TI - [The stenotic-occlusive anatomy and pathology of the renal arteries. Their evaluation by magnetic resonance angiography]. AB - Magnetic resonance angiography of the renal arteries was performed in 10 healthy subjects, 10 patients with renal artery stenosis and 2 patients with accessory renal artery (1 unilateral, 1 bilateral). All patients selected among 35 subjects with suspected renovascular hypertension had previously undergone digital subtraction angiography. Four patients were studied before and after percutaneous transluminal angioplasty. MRA was performed with time-of-flight technique, with 2D and 3D FISP and 2D FLASH gradient-echo sequences. Digital subtraction angiography demonstrated stenoses ranging 40% to 90% in 10 cases, 7 unilateral (1 transplanted kidney) and 3 bilateral. RA correctly depicted > 90% stenoses in 5 cases, between 50% and 90% stenoses in 2 cases and < 50% in 2 cases. Four stenoses were not properly graded (3 over-graded and 1 not visualized because distal to ostium). Diagnostic accuracy was 71% for unilateral stenoses and 66% for bilateral stenoses (overall accuracy 69.2%). PMID- 1410674 TI - [Percutaneous transluminal renal angioplasty of the solitary kidney]. AB - We report on our experience with percutaneous transluminal angioplasty (PTA) of the renal artery in solitary kidney patients. PTA was performed on 31 subjects (mean age: 52 years): 7 had a solitary kidney because of nephrectomy and 24 had a solitary functioning kidney. Patients were selected with clinical and laboratory examinations first and then with angiography. PTA was employed to treat renal artery stenoses 60%-95% of the whole arterial lumen. The procedure has been considered technically successful in 29 cases, with 77%-33% reduction of the mean amount of stenosis. As to the clinical evaluation of the results, blood pressure and creatinine values variations were considered. Of the 25 patients on follow up, 13 appeared to be treated (52%), 8 improved (32%) and 4 unchanged (18%). On the whole, we observed 5 complications (2 hematomas at the approach site, 1 intimal dissection and 2 segmental infarcts), with a 23.4% rate comparable with PTA complications in non-solitary kidney patients. The good revascularization, the reduction in blood pressure values, the very small percentage of complications point to PTA of the renal artery as the procedure of choice in solitary kidney patients. PMID- 1410675 TI - [An evaluation of the N parameter according to the system of the American Thoracic Society (ATS) in pulmonary carcinoma. A comparison between radiology, surgery and histological diagnosis]. AB - The hilar and mediastinal lymph nodes of 36 patients with bronchogenic carcinoma were evaluated with computed tomography (CT). The American Thoracic Society (ATS) mapping was employed, which defines nodal stations in terms of well-recognized anatomic landmarks which are easily identified with CT and during thoracotomy. The differences (30 cases) between CT and surgical measurements in the 124 nodal stations which could be analyzed are discussed in detail. A better correlation was found using a 2-cm threshold value to define a "positive" or "negative" lymph node with CT. The comparison of radiologic data and the presence of metastases showed how with the 2-cm size criterion sensitivity drops from 81% to 53%, whereas specificity rises from 53% to 84%, thus affecting the subsequent diagnosis and therapy positively. PMID- 1410676 TI - [Dosimetric problems and their solution in the preparation of a 6-dual-field total-skin technique]. AB - The six-field total skin electron irradiation (TSEI) technique needs an accurate preliminary dosimetric study. The American Association Physics in Medicine (AAPM) defined a dosimetric protocol that recommends the careful dosimetry of the horizontal, the dual and the six-dual fields by using both a cubic and a cylindrical phantoms. In our Institute, in a TSEI development program, we carried out the preliminary dosimetry according to AAPM criteria. We also investigated some dosimetric problems--e.g., the so-called "cable effect", which takes place when the detector cable in a TSEI field is not well shielded, polarity effects and photon contamination. As to the "cable effect", it is especially marked with the Markus NE2534 chamber; moreover, this effect, if not considered, can lead to overestimation of X-rays contamination. PMID- 1410677 TI - [Conformal technics by the movement of bars in pendular fields. 1. Prototype realization and the possible applications]. AB - The growing interest for conformal radiotherapy originates from the need of giving the prescribed dose to the target volume, by sparing, at the same time, surrounding healthy tissues and organs. More dose to the target volume with respect to the healthy tissues always increases the curative possibilities of the treatment. However, the development of conformal techniques implies an increased complexity of the treatment and the solution of many technical and dosimetric problems. In our Institute we are developing new conformal techniques, based on the use of moving bars driven by a computer-controlled system in arc therapy. This paper refers to the conclusion of the preliminary part of our work: a movement (translating or rotating) of bars in arc therapy seems to have good chances to tailor dose distribution in a relatively simple way. We realized two mechanical systems driven by computer for translating and rotating movements of a bar. The two techniques have been tested by TLD and film dosimetry on acrylic phantoms. We present the results of these tests, and describe technical problems and the clinical possibilities of this method. PMID- 1410678 TI - [Conformal technics by the movement of bars in pendular fields. 2. The dosimetric aspects]. AB - The development of conformal techniques by movement of bars in pendular fields requires a careful examination of many physical and dosimetric problems: bar critical organ synchronization problems, dose calculation problems, and problems relative to the "shadow effect". The use of a bar in an arc field, causes to a slow gradient of dose between shielded zone and target volume with a loss of homogeneity in dose distribution. This effect is well known ("shadow effect") and depends on the fact that different points spend different times beyond the bar's shadow. In this work the problem is investigated in the case of moving bar technique, mainly for dose calculation possibilities; then the possibility is analyzed of optimizing dose distribution by means of filters whose profile can be calculated for simple geometric conditions (fixed bar on the isocenter without considering the profile of the patient). These filters will be made in our Institute and they will be tested in various conditions, for both fixed bars and moving bars in arc fields. PMID- 1410679 TI - [Rhinocerebral mucormycosis. The clinico-radiological aspects of a case with a progressive and fatal course]. PMID- 1410680 TI - [Carbon monoxide poisoning: computed tomography and magnetic resonance of the brain. A case report]. PMID- 1410681 TI - [Ganglioneuroma: the diagnostic procedure in a case of retroperitoneal localization]. PMID- 1410682 TI - [Intestinal infarct: the diagnostic contribution of computed tomography. 5 cases]. PMID- 1410683 TI - [The reduction of a uterovaginal prolapse after the drainage by ultrasound-guided needle aspiration of a voluminous ovarian cyst. A case report]. PMID- 1410684 TI - [A stamp issued by the Austrian postal system commemorating the 150th anniversary of the enunciation of the Doppler effect]. PMID- 1410685 TI - [Mammography and Canadian screening]. PMID- 1410686 TI - Assessing human exposures to pesticides. AB - Pesticide use is inevitably associated with chemical exposures that range from inferred nondetectable levels to easily measurable ones using sensitive, readily available analytical tools. Whether these exposures are of any biological significance is determined by duration, dose, and biological reactivity. The overwhelming majority of human exposures occur in a diverse chemical milieu of a nutritive substances and are of no known significance. Technologies that minimize human chemical exposures and maximize pesticide effectiveness are favored. The risk characterization process is ideally suited to assist decision makers concerning the protection of human health and evaluation of agricultural tools. It is the best means available to balance the review of pesticide impacts on health and agriculture. Regulators must be cautious to acknowledge the relative rather than absolute nature of the risk characterization process. Workplace biological monitoring must become more commonplace as a means to evaluate the chemical exposure potential of various work tasks and greater attention must be given to the biological validation of methods. Earlier needs for data to develop workplace hygiene strategies have been replaced in recent years by demands of the risk assessment process, which utilizes direct estimates of exposure and absorbed dose. Animal models, no matter how attractive, are not presently a substitute for human experience. Opportunities to gather more information on human experience associated with pesticide exposures must be more aggressively identified and pursued. Only a very small time lag should exist between identification of pesticide metabolites in rats and evaluation of metabolic similarities in humans. At the present levels of analytical sensitivity, most of our current uncertainty about the extent of worker exposure and patterns of metabolism between species can be at least clarified with the cooperation of persons who are exposed during normal day-to-day activities in the workplace. Only with better human data will the risk assessment process warrant greater reliance in decision making concerning our chemical exposures and human experience. PMID- 1410687 TI - Biomarkers of pesticide exposure. AB - Incorporation of biomarkers in studies of occupational exposure hazards is now recognized as a highly useful adjunct to the surrogate measures employed in the past, for example, time worked, ambient air data, interview responses. Application to studies of workers potentially exposed to pesticides has barely begun and provides many challenges to chemist/epidemiologist teams. This review indicates several excellent studies employing multiple-exposure measures to document the validity of specific biomarkers for particular exposure situations. In general, exposure reflected by urinary assays of specific pesticides is a low percentage of that indicated by dermal or breathing zone measures. Markers for many of the pesticides in current usage have yet to be developed and validated, and information on population variability is generally lacking for existing markers. The challenge provided by the complexity of multiple, and often unknown, exposures to individuals in pesticide environments has begun to be addressed employing cytogenetic or urinary measures that attempt to integrate these complex exposures. The lack of data regarding sensitivity and specificity of biomarkers, especially in complex exposure situations, is a major problem that perhaps will best be addressed by studies combining nonspecific measures with specific ones, utilizing stored sample banks created for that purpose. Expanding the repertoire of available biomarkers of pesticide exposure and employing multiple ones in well designed study protocols will provide critical tools in the evaluation of pesticide safety and design of appropriate measures to minimize adverse exposures. Ironically, one of the problems that biological markers of exposure can help overcome, reliance on poorly measured ambient exposure data, hampers the evaluation of the markers themselves. Therefore, the combination of in vitro, animal, and human data will give the best picture of a marker's performance. (Wilcosky 1990). PMID- 1410688 TI - Estimating worker exposure for pesticide registration. AB - For the registration procedures of pesticides, the level of exposure during the various activities in which pesticides are handled has to be estimated. Different worker exposure models have been put forward in Europe and North America. These models are discussed and compared to each other for their output in terms of estimated levels of potential inhalation and dermal exposure. It is concluded that the output varies with the model, largely for two reasons. First, the underlying databases are completely different, which is inherent to locally different equipment and farm sizes. Second, the statistic used in the estimation of a level of exposure from a database varies from a geometric mean to the 90 percentile. The estimated levels of exposure may be used in a first step of the risk assessment. It is recommended that the relevant parts of all four models be considered to increase the representativity of the predicted level of exposure. PMID- 1410689 TI - Blood esterase determinations as markers of exposure. AB - The bases of using blood enzyme activity measurements [e.g. AChE, non-specific cholinesterase (BChE), carboxylesterase] as markers of organophosphate ester (OP) exposure are inhibition of activity by the binding of OPs to serine active sites in the enzymes, and the accessibility of the enzymes in RBCs and serum. The methods used to determine esterases in the blood of humans, experimental animals, and wildlife are outlined with emphasis on the acetylcholinesterase (AChE) of the red blood cell. Adaptations of an acetylthiocholine ester assay of Ellman et al. (1961) are common, but other colorimetric procedures, radiometric assays, and pH methods are also in use. Optimized, standardized methods are needed to assess exposures and provide a solid basis for risk assessment analyses. Useful adjuncts to ChE measurements are oxime reactivation tests and assay of neuropathy target esterase, an enzyme associated with organophosphate-induced delayed neuropathy. Determination of urinary metabolites compliments, but does not substitute for, the information obtained from blood ChE studies. Future assays are likely to involve antibodies to OP-protein complexes. Improvements in techniques permit the detection of small decreases in ChE activities. Whether or not such small decreases in ChE activities can, by themselves, constitute an adverse effect for input into risk assessment analyses is a controversial matter. PMID- 1410690 TI - Reentry field data and conclusions. AB - A review of the reported foliar residue data has revealed a number of deficiencies in the reentry intervals currently regulated, in particular, by the EPA and some by California. Deficiencies were also identified in the available information necessary to recommend better reentry intervals. Information regarding the frequency of exposure for individual or groups of harvesters is the most fundamental deficiency. It is needed to define a more realistic chronic criterion of allowable daily cholinesterase inhibition without cumulative symptoms. The second criterion of preventing acute overexposure is more readily defined. For the purposes of this study, the criteria of 4% mean daily inhibition and 50% acute inhibition were chosen as acceptable. Based on these criteria, the available data, and by using the unified field model assessment as the basis for comparison (Table 9), EPA reentry intervals for nine insecticides in Table 4 appear inadequate (i.e., not within the range of the model recommendations); 10 are adequate; and only one appears excessive as summarized in Table 10. A similar comparison of California's reentry intervals indicates only two may be inadequate or marginal; 13 are adequate; and five may be excessive. Although these conclusions are based on a considerable amount of residue data, the data are not equally distributed among all pesticides nor has the model been confirmed in all the cropping and harvest conditions examined. However, the model has been developed under realistic field tests, most of its premises have been confirmed in a limited number of tests, and its simulated predictions appear to parallel experience in California where pesticide use and decay conditions may have been most severe but recently well scrutinized. The model's recommendations largely substantiate the regulations developed in California. However, its conclusions definitely suggest that improved levels of protection are needed in other regions. Future reentry intervals will require more comprehensive residue data. The toxicities of detectable metabolites for a few insecticides will need to be determined. More crop residue dosing coefficients are also needed for manually harvested crops. These data must be interpreted in terms of the potential both for acute poisoning from variable residues and for chronic poisoning from repeated exposure to more consistent residues. Surveys of the temporal exposure patterns of harvesters or crews of harvesters are vital to assess the cumulative effects and set the most appropriate chronic cholinesterase response limits. While we await further data, there is sufficient information now to justify longer reentry intervals to protect harvesters nationally. PMID- 1410691 TI - Pesticide protective clothing. AB - In looking into future directions of "protective clothing" for pesticide users, the final EPA ruling scheduled for release in June 1992 (Smith personal communication) places the majority of its recommendations on the label. Therefore, it will be up to pesticide manufacturers to provide protective clothing information on their products labels. Research on protective clothing continues to show variations due to fabric characteristics of fiber content, fabric construction and finish. These variabilities are compounded by variation s due to pesticide formulation and pesticide chemical and are further compounded by field studies vs laboratory simulations. With hundreds of fabric variations compounded by the thousands of chemical compounds and formulation variations, the consumer cannot be expected to make proper decisions regarding protective clothing. The user of the product does not have the knowledge to select the appropriate clothing. Manufacturers must supply this information, but they must also have data to support recommendations of their clothing for pesticide protection. This shifts the responsibility for recommending adequate protective clothing, as well as the concern for product liability, to the manufacturer. PMID- 1410692 TI - Exposure to pesticide mixer/loaders and applicators in California. AB - Pesticide exposure occurs both when preparing (mixing/loading) the pesticide for application and when actually applying the pesticide. Equipment cleanup and repair may also contribute to exposure. These separate tasks may be done by different people or a single individual may combine them. Different formulations, handling methods, and application methods may affect levels of exposure. Good workplace hygiene dictates that the first priority in workplace safety is to put in place engineering and administrative controls to make the workplace safer rather than rely on the use of PPE to prevent exposure. Providing a physical barrier, such as closed systems for the mixer/loader and an enclosed cab or cockpit for applicators, is associated with reduced exposures of workers. The Worker Health and Safety Branch in the DPR of Cal/EPA has been monitoring various work task exposures. The results of these studies are summarized in Figures 1-4, where exposure is shown based on both time worked and amount of material handled. The studies were done using dosimeters, skin washes/wipes, and air pumps. Water soluble packets, which are very popular with users, surpassed closed systems in reducing exposure to mixer/loaders in these studies. Hand spraying proved to present the greatest risk of exposure of the methods of application studied. It was found that the dermal route of exposure is most important, comprising 87-95% of a handler's exposure. Although this survey cannot be considered conclusive, since it leaves many formulations, systems, and methods incompletely studied or unstudied, it is clear that exposure is affected by different handling strategies. Manufacturers, regulators and users should work more closely to refine or develop new systems for safely handling pesticides. PMID- 1410693 TI - Global estimates of acute pesticide morbidity and mortality. AB - Mathematical models have projected increasing numbers of pesticide poisoning throughout the world, rising from 500,000 cases/yr in 1972 to 25,000,000 cases/yr in a 1990 estimate. Among 148 outbreaks (excluding Bhopal and three probable epidemics of pesticide-related suicide) reported between 1951-90, the known number of cases was 24,731 with 1065 deaths (4.3% case fatality); these are probably underestimates. Among the known outbreaks, the most commonly identified agents were organophosphates (58), carbamates (23), chlorinated hydrocarbons (23), and organic mercurials (11). Food was the most common vehicle of exposure in these epidemics (83 outbreaks), followed by skin contact (26), multiple types of exposure (22), and respiratory exposure (16). Two countries, the United States and Thailand, accounted for more than half the reports. Both the mathematical models and the outbreak investigations support the need for continuing investigation and improved surveillance throughout the world. PMID- 1410694 TI - Acute pesticide morbidity and mortality: California. AB - The California Pesticide Illness Surveillance Program collects, investigates, abstracts, and records reports received from physicians. A minority of the reports are received through the county health officers who are notified by physicians under a state requirement for reporting pesticide-caused conditions. Most of the cases are identified by review of workers' compensation records. All the cases identified are investigated by the agricultural commissioners of the counties where exposure occurred. The investigation reports are reviewed and abstracted by staff of the Worker Health and Safety Branch of the California Department of Pesticide Regulation, California Environmental Protection Agency (Cal/EPA). The crucial determination is assessment of the degree of relationship between the exposure and subsequent disease: definite, probable, possible, unlikely, or unrelated. In most years, the number of cases investigated has been between 2,500 and 3,000. Excluding antimicrobials, the number of cases found after investigation to have a definite, probable, or possible relationship with pesticide exposure has ranged from 970 (in 1989) to 1,372 (in 1988). Cases involving antimicrobials rarely were reported prior to 1987. In that year, surveillance staff began reviewing workers' compensation records personally, with the specific goal of identifying antimicrobial cases. Since then, antimicrobials have been found to account for 746-813 cases annually, primarily involving splashes and squirts to the eye and inhalation of fumes or vapors. Numbers of case reports from agricultural situations have varied irregularly, driven by small numbers of episodes concerning multiple individuals. Variability in numbers of cases involving the skin has depended almost entirely on variation in numbers of field worker dermatitis. The most common situation for field worker dermatitis has been summer work in table grapes grown in the southern San Joaquin valley. In the two years since reentry intervals for the acaricide propargite were lengthened, there have been no more major clusters of field worker dermatitis. Although the cases collected by the surveillance program are predominantly occupational, because of dependence on workers' compensation for case identification, most recorded deaths are nonoccupational. Nonoccupational fatalities include suicides, mistaken ingestion of pesticides (especially if stored in food containers), and entry into structures being fumigated. Occupational deaths are less common and more varied. The circumstances of each reported occupational death are summarized above. PMID- 1410695 TI - Challenges in assessing long-term health effects studies. AB - After almost 50 yr since modern synthetic pesticides first received wide-spread use in the USA, many of the challenges that need to be met in determining their long term effects on human health remain unanswered. Answers to many of the key challenges, such as accurate exposure assessment, pesticides' role in multifactorial causation of disease, latency, publishing of negative results, misclassification, low-level dose measurement, accurate diagnosis, the role of biomarkers, adequate study design, and adequate funding, will continue to be key factors in investigating the role, if any, of these chemicals in the transmission of human diseases. PMID- 1410696 TI - Comparison of exposure assessment guidelines for pesticides. AB - The field of exposure assessment of pesticides has become well established in the past decade. Consequently, government agencies and industry groups have identified the need for guidelines for conducting studies that assess mixer/loader/applicator exposure to pesticides, as well as the exposure of individuals to residues. This paper reviews guidelines on mixer/loader/applicator exposure studies issued by the International Group of National Associations of Manufacturers of Agrochemical Products, the National Agricultural Chemicals Association, the U.S. EPA, and the World Health Organization. Mention is also made of Canadian exposure guidelines in preparation. Also reviewed are two guidelines for conducting indoor occupant exposure studies, one by the National Agricultural Chemicals Association and one by Health and Welfare Canada. The only available guideline (EPA) on assessing pesticide exposure to workers upon reentry into treated fields is also reviewed. These guidelines are reviewed and compared as to criteria for requirements of exposure studies, methodologies recommended for dermal, inhalation, and biological monitoring, quality assurance and quality control, the use of surrogate data, data reporting, and exposure calculations. From this comparison, it is evident that there has been little significant progress in the area of methodologies used for dermal exposure monitoring. The use of patches as suggested by Durham and Wolfe (1962) is still accepted and widely used, despite its limitations. However, relatively recent research in this area has shown that the fluorescent tracer technique (Fenske et al. 1986a,b) and use of full-body dosimeters may help in overcoming some of these limitations. The tracer technique is mentioned in the EPA guidelines and full-body dosimeters are addressed by EPA, WHO, and NACA. Biological monitoring can also overcome many of the limitations of passive dosimetry, but all guidelines stress the need for extensive knowledge of the pharmacokinetics and metabolism of the pesticide before this approach can be used. Rapid advancement has been made in quality assurance/quality control and analytical techniques. This has increased the level of confidence placed in exposure estimates and is evidenced by the detailed requirements of quality assurance and quality control in most of the guidelines reviewed. Guidelines on conducting indoor occupant exposure studies deal extensively with methodologies for collecting residue samples, but do not make concrete recommendations for estimating human exposure based on these residues. More research is required before the subject can be adequately dealt with in guidelines. It is encouraging that this research is being coordinated among industry, academia, and government. Further research is also needed in determining exposure to pesticides during reentry into treated areas in order to develop further guidelines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1410697 TI - Saliva as a monitoring medium for chemicals. AB - Saliva has been used to estimate plasma levels in humans for a variety of analytes. The potential for estimating the internal dose of pesticides in humans has been demonstrated with the rat. The utility and problems of saliva-sampling techniques remain to be investigated. Measurement of pesticides and other environmental toxicants in saliva has great potential because of sampling simplicity and the potential accuracy of using the saliva concentration of a chemical to estimate its concentration in human tissues. PMID- 1410698 TI - [Guidance of tooth eruption in the support areas using proximal grinding]. AB - This article brings a description of a procedure for interproximal slicing. When persistence of the second deciduous molar occurs, the premolar is likely to be blocked in his eruption, while the canine is guided out of the dental arch; in these conditions it might be necessary to perform a slicing mesially of the second deciduous molar. Beforehand one should check for the posterior tooth-size and eruption pattern or sequence of each quadrant. PMID- 1410699 TI - [Approach to pulpal and pulpo-periodontal lesions of the temporary teeth using therapeutic endodontics]. AB - The anatomical and physiological properties of deciduous teeth make them susceptible to caries and inflammatory and infectious complications. This specificity, the proximity of the germ of the underlaying permanent tooth, and the relation of the last one to the deciduous tooth, make delicate its conservation by endodontal therapeutics after a pulpal or pulpo-periodontal affection. The success of this attempt is related to a good case-selection, based on the general condition of the child, his and his parents motivation, the condition of cariogenicity of the mouth, the analysis of the unity deciduous tooth/germ of the underlaying permanent tooth, the follow-up of the case. A success spares young children extraction of the deciduous teeth before the physiological period of permutation. PMID- 1410700 TI - [Observations on prosthetic restoration in children]. AB - In young children there are two frequent factors, that cause edentation: the syndrome of the sugar "baby's bottle" or the "honey dummy" and tooth-loss by trauma. Multiple extractions can be programmed in children for reason of general condition, in the major concern to remove present or potential infectious foci. Still less frequently, sometimes lately diagnosed anomalies in number or structure oblige to replacement of missing or deficient tooth. The complexity of these restorations can be related to technical problems, less frequent, in contradiction to the current opinion, to psychological problems. They have to be integrated in structures in growth, the key character of each treatment in children or adolescents. Consequently it is necessary to take account of all this factors, before to attempt this charge, and to foresee adaptations, regular control, succession of the case and interception. PMID- 1410701 TI - [Glass ionomer cements in children]. AB - Glass-ionomer cements are becoming more and more popular in restorative dentistry. This paper describes their principal characteristics and their use in children's dentistry; a pictorial essay illustrates some possible clinical applications. PMID- 1410702 TI - [Multi-caries in the young child]. AB - This article describes the clinical and therapeutic aspects of multi-caries in young children. These rampant cervical caries usually begin with the eruption of the first teeth. Two typical cases are presented in which the prolonged use of nursing bottle at bedtime and the use of pacifiers dipped into honey are responsible for the development of multi-caries. Although such patient can be treated successfully, efforts should be made to promote preventive measures and parents education. PMID- 1410703 TI - [Space maintenance following the premature loss of temporary teeth]. AB - Despite contemporary techniques, we still don't have the ability of saving all deciduous teeth in their place on the dental arch until the time of physiological loss. A premature loss of temporary teeth interferes with the harmony of the adult dentition. The principal consequence of this premature loss is crowding, caused by migration of the adjacent teeth. This article ames to guide our policies in the decision making process whether or not maintaining space, in causes of premature loss of one or more deciduous teeth. PMID- 1410704 TI - Poorer is riskier. AB - To examine the relationship between economic well being and health status, two economic concepts were explored: the permanent-income hypothesis and the transitory-income hypothesis. A regression analysis of time-series mortality data for the period of 1950-1988 was conducted. The regression results indicated that the total mortality rate is negatively associated with permanent income and positively associated with the transitory income. Results are also reported for the 8 major causes of death in the United States. The implications for risk analysis are discussed. PMID- 1410705 TI - Risk to groundlings of death due to airplane accidents: a risk communication tool. AB - During the period 1975-85 in the United States the 70 year lifetime risk of dying from being hit by an airplane when the individual is on the ground was 4.2 per million people. In contrast to many other risks used for comparison purposes, risk to those on the ground from an airplane crash is not a function of our own skills; is not optional; provides no benefit to anyone involved; and is not an act of nature. As a risk comparison tool it also has the useful characteristics of being something about which we can agree that regulatory action, such as control of airplane use and traffic, is warranted; but that no significant change in personal behavior, such as living in the basement to protect against dying from a plane hitting the home, is commensurate with the extent of risk. PMID- 1410706 TI - Risk, statistical inference, and the law of evidence: the use of epidemiological data in toxic tort cases. AB - Toxic torts are product liability cases dealing with alleged injuries due to chemical or biological hazards such as radiation, thalidomide, or Agent Orange. Toxic tort cases typically rely more heavily than other product liability cases on indirect or statistical proof of injury. There have been numerous theoretical analyses of statistical proof of injury in toxic tort cases. However, there have been only a handful of actual legal decisions regarding the use of such statistical evidence, and most of those decisions have been inconclusive. Recently, a major case from the Fifth Circuit, involving allegations that Benedectin (a morning sickness drug) caused birth defects, was decided entirely on the basis of statistical inference. This paper examines both the conceptual basis of that decision, and also the relationships among statistical inference, scientific evidence, and the rules of product liability in general. PMID- 1410707 TI - Biological markers of environmental and ecological contamination: an overview. AB - An approach, using biomarkers (biological responses) for assessing the biological and ecological significance of contaminants present in the environment is described. Living organisms integrate exposure to contaminants in their environment and respond in some measurable and predictable way. Responses are observed at several levels of biological organization from the biomolecular level, where pollutants can cause damage to critical cellular macromolecules and elicit defensive strategies such as detoxication and repair mechanisms, to the organismal level, where severe disturbances are manifested as impairment in growth, reproduction, developmental abnormalities, or decreased survival. Biomarkers can provide not only evidence of exposure to a broad spectrum of anthropogenic chemicals, but also a temporally integrated measure of bioavailable contaminant levels. A suite of biomarkers are evaluated over time to determine the magnitude of the problem and possible consequences. Relationships between biomarker response and adverse ecological effects are determined from estimates of animal health and population structure. PMID- 1410708 TI - The application of bioassays in risk assessment of environmental pollution. AB - Increased contamination of the environment by toxic chemicals has resulted in the need for sensitive assays to be used in risk assessment of polluted sites. Traditional tests are useful to detect and measure concentrations of chemicals in the environment and in tissues. However, physicochemical assays possess deficiencies that impair their use in evaluating complex environmental contamination. We have developed cytogenetic procedures, including chromosomal, micronucleus, and flow cytometric assays, to assess the mutagenic damage of petrochemicals and low-level radioactivity on indigenous terrestrial and aquatic wildlife populations. These procedures are sensitive to the perturbation of DNA that results from exposure to mutagenic contaminants in both field and laboratory studies. The use of natural populations of animals in biomonitoring, combined with traditional chemical assays, will ultimately provide sufficient information to estimate the risk to human health and environmental quality from anthropogenic pollution. PMID- 1410709 TI - Reassessing benzene cancer risks using internal doses. AB - Human cancer risks from benzene exposure have previously been estimated by regulatory agencies based primarily on epidemiological data, with supporting evidence provided by animal bioassay data. This paper reexamines the animal-based risk assessments for benzene using physiologically-based pharmacokinetic (PBPK) models of benzene metabolism in animals and humans. It demonstrates that internal doses (interpreted as total benzene metabolites formed) from oral gavage experiments in mice are well predicted by a PBPK model developed by Travis et al. Both the data and the model outputs can also be accurately described by the simple nonlinear regression model total metabolites = 76.4x/(80.75 + x), where x = administered dose in mg/kg/day. Thus, PBPK modeling validates the use of such nonlinear regression models, previously used by Bailer and Hoel. An important finding is that refitting the linearized multistage (LMS) model family to internal doses and observed responses changes the maximum-likelihood estimate (MLE) dose-response curve for mice from linear-quadratic to cubic, leading to low dose risk estimates smaller than in previous risk assessments. This is consistent with the conclusion for mice from the Bailer and Hoel analysis. An innovation in this paper is estimation of internal doses for humans based on a PBPK model (and the regression model approximating it) rather than on interspecies dose conversions. Estimates of human risks at low doses are reduced by the use of internal dose estimates when the estimates are obtained from a PBPK model, in contrast to Bailer and Hoel's findings based on interspecies dose conversion. Sensitivity analyses and comparisons with epidemiological data and risk models suggest that our finding of a nonlinear MLE dose-response curve at low doses is robust to changes in assumptions and more consistent with epidemiological data than earlier risk models. PMID- 1410710 TI - The use of generalized estimating equations for risk assessment in developmental toxicity. AB - This paper reviews and compares several approaches to fitting dose-response models to developmental toxicity data. The main issue of interest is how to appropriately account for litter effects. Among the approaches reviewed are Beta Binomial models, models that attempt to characterize the litter effect through the use of covariates, and models that avoid the complication of correlated offspring by modeling "affected litter" rather than fetus-specific outcomes. Finally, we discuss our recommended approach, which is to use Generalized Estimating Equations, or quasi-likelihood. We give a number of reasons for preferring the latter and illustrate its application with an example. PMID- 1410711 TI - A content analysis of written behavior management programs. AB - A method is described for assessing the elements of individual behavior management programs. The content analysis, consisting of 24 items covering the general categories of behavior specification, objectives, program procedures, data collection, and quality assurance, was applied to 141 written behavior programs of two large institutions from different regions of the United States. These data can be utilized readily to establish a data base for program evaluation at both the individual and institutional levels. In addition, to provide a measure of validity, the items included in the content analysis were rated by experts in the treatment of severe behavior disorders. General strengths and weaknesses of the programs, and of the content analysis itself, are discussed in light of their implications for program implementation and evaluation. PMID- 1410712 TI - Assessment and training of functional conversation behaviour. AB - Measures for the assessment of initial, dyadic conversations are critically reviewed, and an alternative approach is described. The Verbal Interaction Analysis System is illustrated by two case studies featuring mildly to moderately intellectually disabled adults. These studies show how the VIAS provides an index of competence and assists in the development of specific treatment strategies. Social validity is examined in each case, and suggestions are made for improvements to the VIAS. PMID- 1410713 TI - Components of personal competence and community integration for persons with mental retardation in small residential programs. AB - This study identifies components of personal competence and community adjustment in a national sample of persons with mental retardation living in residential facilities of six or fewer residents. Factor analysis of 65 variables yielded an 8 principal component solution that accounted for approximately half the total variance in the observed variables (49%). The eight identified components of personal competence and community adjustment were labeled (1) Self Care and Functional Personal Living Skills, (2) Community Living Skills, (3) Home Living Skills, (4) Problem Behavior, (5) Community Training Goals and Objectives, (6) Recreation/Leisure Activity, (7) Family Contact/Relationships, and (8) Community Assimilation and Acceptance. The implications of reducing potentially hundreds of indicators of personal competence and community adjustment into relatively few broad internally consistent composite constructs are discussed. PMID- 1410714 TI - Translation, cultural adjustment, and validation of a measure of adaptive behavior. AB - This paper investigates whether a measure of adaptive behavior, which has been developed and validated in western countries, could be successfully adapted to a nonwestern country, Indonesia. The purposes of the study were to (a) delineate procedures for cross-cultural adaptation and validation of adaptive behavior measurement, (b) create an operational version of an instrument in an Indonesian setting, and (c) investigate the validity of the resultant instrument by studying whether it had the same psychometric properties as its United States counterpart. The results are discussed in terms of the usefulness of the methodology employed for ascertaining the worth of any operationalizations of constructs and themes borrowed from other cultures that will form the basis for educational program development and individual pupil assessment. PMID- 1410715 TI - [De Quervain's tenosynovitis. Transversal scar and fixation of the capsular flap]. AB - The authors report 62 cases of De Quervain tenosynovitis treated from 1983 to 1990 by the same surgeon. The de Quervain's tenosynovitis is an inadequation between the volume of the abductor pollicis longus and the extensor pollicis brevis and their tunnel above the radial styloid process producing a mechanical tenosynovitis. This disease occurs mostly in women with an average age of 47 and almost never before the age of 30. Clinically the patients have pain and swelling above the radial styloid process. Most of the surgeons know today this disease, nevertheless complications may occur (Abductor pollicis longus luxation, disgratious enlargement and adhesion of the scar). The transversal incision provides a less disgracious scar. As the tendinous pulley is opened frequent anatomical variations of the tendons are found. A ventral capsular flap fixation with a subcuticular continuous suture is made. This fixation prevents any ventral luxation. Radial nerve neuromas or neuritis is constantly looked for. The authors expose and analyse the statistical data of this intervention's results with a 6 month minimal and 7 years maximal follow up. PMID- 1410716 TI - [Quintus varus supraductus. Results of the surgical treatment by cutaneous graft, internal capsulotomy and external transfer of the extensor of the 5th toe]. AB - The overlapping fifth toe has often a congenital origin. It may be isolated or associated with an another pathology, congenital or acquired, but the relationship between them. Cannot be ascertained. The overlapping fifth toe is responsible for an esthetic deficit and/or a functional discomfort, it justifies a correct surgery. Twenty-one feet in 16 patients aged from 2 to 30 years (especially between 5 and 15 years) have been operated on and reviewed after a mean follow-up of 4 years. The technic associated a cutaneous dorsal Z-plasty on the cutaneous retraction a medial and dorsal capsulotomy of the metatarso phalangeal joint, an external transfer of the fifth extensor tendon or its tenotomy and, in 10 cases, a plantar skin resection 19 results were excellent, one fair result and one failure. The condition of a stable result seems to be based on a complete and spontaneous correction of the deformity at the end of the operation. PMID- 1410717 TI - [Localizations of histiocytosis X in bone]. AB - Histiocytosis X is still of unknown origin. Its clinical patterns are various and it is above all a bone disease of children, mostly boys. It is a tumoral condition basically benign but with a strong tendency toward dissemination and destruction. Its natural history is unpredictable. The authors have reviewed 37 cases after a 44 months mean follow-up for bringing up a better understanding of the role of orthopedic surgery. The diagnosis was always based on biopsies looking for at least two basic signs out of four possible ones. Scintigraphy was used to detect other locations. MRI was used to evaluate the effect of treatment. In single eosinophilic granuloma, curettage was associated with biopsy. Local injections of corticoids may help in spinal locations. In disseminated forms, surgical treatment should be little aggressive, limited to a biopsy of the most superficial lesion. These forms should be treated by radiotherapy corticotherapy and chemotherapy, as well as the aggressive lesions, the extensive ones, the threatening ones and those which are not accessible. PMID- 1410718 TI - [Remodeling of the spinal canal after comminuted fracture of the spine. Apropos of a case]. AB - A burst fracture of T 12, without neurological impairment, was treated by plaster cast. Prior to treatment, there was a significant narrowing of the spinal canal, due to posterior displacement of a bone fragment. This was not modified by treatment, as the narrowing was unchanged on the second CT scan, done eight days later. At 17 months, there was no more narrowing on the CT scan, as a consequence of vertebral body remodeling. The patient had no pain and performed several sport activities. PMID- 1410719 TI - [Dislocation of the tibialis posterior tendon]. AB - The authors report a case of traumatic dislocation of the tibialis posterior tendon on the medial malleolus. They describe the treatment applied and made a review of the literature about this rare pathology. PMID- 1410720 TI - [Idiopathic chronic retraction of the deltoid muscle. Apropos of 3 cases]. AB - Three cases of a previously undescribed condition of idiopathic, non-progressive deltoid muscle contracture are reported. The clinical features are presented as also the management of the cases. Intra-operative appearance of the fibrotic band responsible for the pathology is described. The relevant literature is reviewed. Though such cases are rare, they show striking features which enable them to be distinguished from other causes of scapular winging. Surgical excision of the band confers lasting correction of the deformity. PMID- 1410721 TI - [Osteochondritis dissecans of the acetabulum. Apropos of a case]. AB - Osteochondritis dissecans acetabuli is a rare affection. The observation presented is one of a 23 year old man, who presented hip blockages in external flexion rotation. X-ray only allowed to find a sequestrum in the acetabulum by tomography-Arthroscanner confirmed the osteochondritis without cartilage rupture. Arthroscopy eliminated a cartilage lesion and directed towards a cavity filled by spongious bone through an extra articular approach. PMID- 1410722 TI - [Cement wedge replacing iliac graft in tibial wedge osteotomy]. AB - The authors report their experience in substituting cement for full-thickness iliac crest wedge in medial tibial wedge osteotomy using buttress plate fixation. A review of 107 osteotomies performed between January 1985 and March 1989, demonstrated that using cement wedge do not expose to any special complication and raise the accuracy of frontal mechanical axes correction. At last, cement wedge seems not to evolve as a stranger corpus able to give long or mean terms complications; it perhaps make unnecessary bone substitute or allografts wedges. PMID- 1410723 TI - [Comparison of the mechanical qualities of cortical bone preserved by cryopreservation]. PMID- 1410724 TI - [Congenital asymmetrical pelvis. Clinical, radiological study and outcome]. AB - In congenital pelvic obliquity, there is a restricted abduction in one hip and an abduction contracture in the other. This association has been considered as a cause of acetabular dysplasia with progressive subluxation of the hip opposite to the abduction contracture. The clinical and radiological study of 120 children with an average follow-up of 3 years and 3 months permitted to demonstrate that two different types exist: the simple types (93 cases) without dysplasia, which never developed progressive subluxation and must not be treated, and the pelvic obliquities with dysplasia-subluxation-dislocation (27 cases) which have to be treated if the decentration of the hip opposite to the abduction contracture is marked. Distinguishing between these two types may be difficult because the X-ray is nearly never strictly correct because of the pelvic obliquity. This work leads to a better comprehension of the acetabular dysplasias who are subdivided into pseudodysplasias, secondary dysplasias and primary dysplasias. In the screening for the detection of congenital dislocation of the hip, it is essential that a pelvic obliquity be recognised because it constitutes a sign of hip at risk. Then, the clinical research of instability could be completed by echographic study in the two or three months or by radiographic study after 3 months in order to have a very precise diagnosis and apply the best treatment. PMID- 1410725 TI - [Surgical treatment of dislocations and subdislocations of the hip in patients with cerebral palsy by femoral and pelvic osteotomy]. AB - Fifty-one skeletally immature cerebral palsied (C.P.) children with 70 subluxated or dislocated hips were treated by conservative methods: femoral osteotomy (65 hips), pelvic osteotomy (52 hips) and arthrotomy when necessary (19 cases). 31 children were less than 10 years of age when operated on (mean 6 years, 6 months), 20 children were more than 10 years of age (mean 13 years, 13 months); mean follow-up was 4 years. Reduction and coverage were achieved and maintained in all patients, except for 6 redislocations: a pelvic obliquity was neglected in 3 cases; femoral shortening was not performed in 2 cases. Post-operative course was difficult in eldest patients with pain and stiffness but functional result was acceptable at follow-up in all cases except redislocations. Open reduction was related to a higher rate of postoperative rehabilitation problems. Modeling of previously deformed femoral heads and improvement of hip mobility were consistently seen at last follow-up, except for 3 redislocations. It is concluded that conservative methods are quite advisable in CP children and adolescents. Hip reduction should be preferred to femoral resection even in adolescent. PMID- 1410726 TI - [Caput valgum in children. Natural history and treatment of a series of 17 hips that reached skeletal maturation]. AB - The growth disturbance of the superior end of the femur which is related to a superior lateral epiphysiodesis of the femoral neck is known as caput valgum (C.V.). Most often, it appears after the treatment of a congenital dislocation of the hip (C.D.H.) which can also produce many other growth disorders of the hip. Fifteen children (seventeen hips) presenting similar evolution and morphological abnormalities have been reviewed. We performed nine surgical procedures most of the time for painful hips because of excentration of the femoral head. When the bone maturity was acquired all hips except two (sequelae of infections) were asymptomatic with femoral heads well covered. When discovered or suspected, this disease needs of careful follow-up. When operative treatment is necessary, we think that it has to be a pelvic surgery. We performed 4 times a triple pelvic osteotomy; 3 times a Chiari osteotomy; and twice a hip shelf arthroplasty. Those operative treatments have always been done with good results in our review. PMID- 1410728 TI - [Patient-controlled anesthesia in postoperative pain]. PMID- 1410727 TI - [Neurological complications of surgery for spinal deformities]. AB - The aim of this study was to precisely analyse the physio-pathogenic mechanisms, bring to light the risk factors, and find a more practical way of proceeding in spinal surgery. Out of 667 spinal instrumentation surgical operations carried out between 1980-1989, we found 33 (4.8 per cent) neurological complications and have divided them into 2 groups: 7 peripheral complications, 26 cord and central complications. After further analysis, especially of the cord complications (2.5 per cent), we were able to pick out the factors which influence the rate of neurological complications and their evolution: secondary aetiology and the kyphotic composition of spinal deformation, and above all the notion of cord at risk. The delay of cord complications and especially the relation between the severity of the neurological syndrome and its evolution is extremely important. Somesthesic evoked potential monitoring confirmed that per operative diagnosis of a cord injury is possible. The steps to take when confronted with neurological complications, depend on the results of many examinations: pre and post-operative neurological evaluations electrophysiological exploration of the cord and neuro radiological explorations (myelography, scanner and IRM). This helps to complete aetiology and eliminate mechanical causes, which are the only positive indications of iterative surgery. The problems of instrumentation removal in emergency and the legal-medical aspect brought on by this type of complication are discussed. PMID- 1410729 TI - [Administration of lysine acetylsalicylate and meperidine in acute postoperative pain]. AB - INTRODUCTION: Postoperative analgesia is insufficiently done due, among others, to the undesirable effects of analgesic agents. OBJECTIVE: The aim of this study was to analyze the effects of the simultaneous administration of opiates (meperidine) and AINES (lysine acetylsalicylate, ASL). MATERIAL AND METHODS: We studied 160 patients during the immediate postoperative phase. All of them underwent programmed surgery with the same general anesthetic technique. Patients were allocated into 8 groups of treatment: A) ASL 900 mg and 1.800 mg/8 h, B) ASL 900 mg and 3.600 mg/8 h, C) ASL 900 mg and meperidine 100 mg/8 h, D) ASL 900 mg and 1.800 mg/8 h together with meperidine 100 mg/8 h, E) meperidine 50 mg and ASL 1.800 mg/8 h, F) meperidine 50 mg and ASL 3.600 mg/8 h, G) meperidine 50 mg and 100 mg/8 h, and H) meperidine 50 mg and 100 mg/8 h together with ASL 1.800 mg/8 h. The effects of analgesic agents were evaluated on the basis of patient's appreciation of the degree of pain and relief and on the basis of an observer who did not know the therapeutic regime administered. Results were compared according to the analysis of variance in a graded factorial design. A p value less than 0.05 was considered significant. RESULTS: The degree of pain was significantly lower in groups C, D, G and H (specially in G and H) than in the remaining groups, but there were no significant differences between them. The lowest pain relief was observed in groups A, B, E and F. The highest attenuation of pain was achieved in groups G and H. The highest attenuation of pain was achieved in groups G and H. The observer considered that the two latter groups were those with the highest pain relief, followed by groups C and D. The remaining patients failed to show appreciable improvement. Nausea and vomiting only occurred in some patients after administration of a bolus of meperidine. There were no other secondary effects. CONCLUSIONS: The best degree of postoperative analgesia is achieved after administration of continuous infusion of meperidine 100 mg/8 h. Simultaneous infusion of ASL 1.800 mg/8 h did not improve the analgesia obtained with a bolus of 900 mg of ASL nor with a bolus of 50 mg of meperidine. Secondary effects were only nausea and vomiting and coincided with the administration of a bolus of meperidine. PMID- 1410730 TI - [Postoperative analgesia using the intravenous PCA technique. Results in the first 400 patients treated at a general hospital]. AB - INTRODUCTION: PCA (patient controlled analgesia) has represented a remarkable advance in the treatment of postoperative pain. In this work we describe our experience with this analgesic technique. MATERIAL AND METHODS: One hundred patients undergoing thoracic and abdominal surgery were selected after giving information to the medical and nurse personnel. Pharmacologic agents used in this study were morphine (intravenous PCA) and fentanyl (epidural PCA). Starting of the perfusion pump was done by the anesthesiologist at the Recovery Unit and the treatment was continued by the nurse. Every morning the patients were visited and the degree of analgesia was recorded according to the following score: 1: no pain, and 5: intolerable pain. An anesthesiologist was permanently available. Later on, this study was expanded to 400 patients including other types of surgery. RESULTS: Mean duration of the treatment was 60 hours. The amount of analgesics administered varied among patients and was greater during the first postoperative hours specially in the group of patients treated with fentanyl. The mean degree of pain was 1.5 (grade 1 in 37.5% of cases and grade 5 in 3.5% of patients). Secondary effects were only nausea and vomiting. Inconvenient features of the technique were: patient's difficulties in the management of the technique (3 cases), and spontaneous loss of the program (1 case). Patient's acceptance of the technique was good. CONCLUSIONS: PCA analgesia has been successfully introduced in our hospital since it is effective, safe, easy to manage. PMID- 1410731 TI - [Comparative analysis of the criteria for surveillance and monitoring in anesthesia, resuscitation and pain therapy. Recommendation of the Sociedad Espanola de Anestesia y Reanimacion]. AB - INTRODUCTION: One part of morbidity and mortality associated with anesthesia is due to accidents. It is thought that an additional monitoring can prevent and avoid most of anesthetic accidents. OBJECTIVES: In order to improve patient's safety and quality of anesthesia, Harvard University hospital approved in 1985 the rules for intraoperative monitoring. These were adopted by the American Society of Anesthesiologists (ASA) in 1986. In line with this procedure, professional associations of several countries pronounced their own rules. SEDAR did it in 1989. The purpose of this study was to compare spanish rules with those of America (Harvard and ASA), Australia, England and France. RESULTS: Comparative analysis revealed that the spanish norms are more extensive since they include not only the intraoperative anesthetic activities, but also those related to recovery, pain, and obstetric anesthesia. However, it has some deficiencies such as the lack of a periodical revision, and of an adaptative period and assistance to the anesthesiologist provided by auxiliary personnel. Successful points were the recognition that pulse oximetry is essential, the preoperative verification of all material, and, more importantly, is the only one that considers essential capnography in the assessment of ventilation and pulse oximetry during regional anesthesia and postoperative phase. CONCLUSION: Spanish norm is comparable to that of the other countries considered in this study. It shows important successful points and at the same time some significant deficiencies. PMID- 1410732 TI - [Thalassemic syndromes and anesthesia]. AB - Thalassemic syndromes are produced by a quantitative defect in the synthesis of globin chains of hemoglobin. They are classified according to the severity of the clinical picture and to the type of globin chain that is affected. Physiopathology, clinical picture, and treatment of thalassemias are discussed in this work. Thalassemia minor does not create, in general, anesthetic problems. In cases of thalassemia major one should consider not only problems derived from the severity of the anemia it self, but also those related to transfusional therapy, and to bony malformations that may disturb tracheal intubation. Discussion on the management of homozygotic thalassemia during the pre, per, and postoperative phase completes this revision. PMID- 1410733 TI - [The introduction of chloroform anesthesia in Madrid. Notes for studying its history]. AB - Until present, the introduction of chloroform anesthesia in Madrid has not been specifically studied by any author. Therefore, knowledge of the events related to this happening is lacking. We have studied this chapter of our history by analyzing primary documents and articles published at the daily press, political press, and scientific journals of Madrid during 1847 to 1848. This investigation allowed us to follow the most relevant news dealing with the discovery of the drug and with its first experimental and clinical applications in Madrid. Based on the present bibliographic material we could establish a chronologic report of all surgical interventions using chloroform that were performed in Madrid. We conclude that albeit surgeons in Madrid were not the first to use chloroform in Spain, they were, however, the ones who most extensively used it. Their contribution was of relevance in the settlement of the new anesthetic agent in Spain. PMID- 1410734 TI - [Tracheal rupture during a transhiatal esophagectomy without thoracotomy. Intra- and postoperative treatment]. AB - We report the case of a male patient with a carcinoma of the upper third of the esophagus who presented a tracheal rupture during a transhiatal esophagectomy. The clinical picture was characterized by a severe alteration of the ventilatory function that required selective intubation and, later on, a right thoracotomy for repairing the tracheal lesion. After surgery the patient was treated at the Recovery Unit. He received high-frequency mechanic ventilation (jet ventilation type) during nine days in a attempt to decrease the risk for dehiscence of the tracheal suture and to ensure an adequate oxygenation and hemodynamic control. The clinical course was favourable. PMID- 1410735 TI - [Pain caused by brachial plexus injury during coronary revascularization. Report of 3 cases]. AB - We report three cases of injury of the brachial plexus after coronary revascularization surgery. During the postoperative phase all patients presented plexopathy involving the left C8 and D1 roots. The symptoms were pain, paresthesia, and motor deficits. The proposed mechanisms for injury of the brachial plexus during cardiac surgery are: hyperabduction of the arm, direct traumatism produced by the needle during catheterization of the internal jugular vein, and traction and compression associated with sternal retraction. In the three patients we ruled out alterations during cannulation of the internal jugular vein and malposition of the arms. We think that in our cases the fundamental mechanism was an excessive and assymetrical opening of sternal and Favoloro's separators that were used in all cases during dissection of the left internal mammary artery. We conclude that injury of the brachial plexus can be minimized by reducing the opening of both separators and by placing Favaloro's separator in a lower position. PMID- 1410736 TI - [Experience with the Du Pen epidural catheter in chronic cancer pain]. AB - We evaluate the results obtained with the use of Du Pen's epidural catheter in a series of patients with chronic oncologic pain. There were 27 patients with neoplasms of different etiologies who received a total number of 30 catheters. Inclusion criteria were established. All patients received bolus of morphine chloride free of conservers. Follow-up controls were carried out at least every week and consisted on the evaluation the dosage efficacy, dose adjustments, catheter condition, physical activity, neurologic state, and requirements of adjuvant medication. The documented use of the 30 catheters implanted in this study lasted up to 1452 days with a mean of 48.5 days. There were no complications related to catheter insertion. However we observed complications related to the use of the catheter: reflow at the site of catheter implantation in 4 cases, infection of the external (one case) and internal (one case) catheter route without antibiotic resolution, and infection of the epidural space responding to antibiotherapy without catheter withdrawal in one patient. Twenty patients died. Mortality was not attributed to catheter complications in any case. The present study confirms that placement of the catheter is technically easy and provides an efficacious opiate analgesia with minimal complications. PMID- 1410737 TI - [Adverse effects of the administration of opiates by the spinal route]. PMID- 1410738 TI - [The work of Juan Vicente Hedo]. PMID- 1410739 TI - [Asystole during the removal of an epidural catheter]. PMID- 1410740 TI - [Transient pneumothorax caused by carbon dioxide following laparoscopy]. PMID- 1410741 TI - [Myoclonus of the legs as a complication of spinal morphine]. PMID- 1410742 TI - [Alternative method when confronting an intubation failure in emergency obstetric anesthesia]. PMID- 1410743 TI - [Aortobifemoral shunt and exeresis of 2 paragangliomas in the same surgical procedure]. PMID- 1410744 TI - [Catastrophic pulmonary vasoconstriction]. PMID- 1410745 TI - [Obtaining organs for transplantation]. PMID- 1410746 TI - [Epidemiology of head traumas. "Barcelona" data base. Objectives, design and analysis of 584 cases]. AB - INTRODUCTION: Descriptive analysis of some features in patients with cranio encephalic traumatisms (CET) admitted to our hospital and collected in a data base, in order to establish the prognosis of the lesions and apply the most appropriate diagnostic and therapeutic procedures. MATERIAL AND METHODS: Since July 1987 to June 1989 we collected data on 584 patients with CET who presented the following selection criteria: consciousness level lower than 13 points in the Glasgow scale and/or pathologic computerized tomography. According to the consciousness level (Glasgow scale) on admission, patients were classified into three groups: slight CET (Glasgow 15-13), moderate CET (Glasgow 12-9), and severe CET (Glasgow < 9). The traumatic mechanisms were divided into 8 categories (occupant, pedestrian, motorbike, aggression, labor, drop, sporting, cyclist). According to the main lesion we considered the following diagnoses: subdural hematoma, epidural hematoma, cerebral contusion (s), diffuse lesion with normal computerized tomography and/or subarachnoid hemorrhage, cerebral congestion, and diffuse axonal lesion. Results were evaluated six months after using the Glasgow scale. RESULTS: The mean age of patients with slight CET was 37.7 +/- 22.1 years, those with moderate CET 31.7 +/- 22.6 years, and those with severe CET 30.8 +/- 21.6 years. Four hundred and forty-two were men (75.6%). The time period between the accident and hospital admission could be determined in 512 cases (87.6%). Severe CET arrived to the hospital (4.8 +/- 7.3 hours) earlier than the other groups (6.6 +/- 11.9 hours in moderate CET and 14.2 +/- 23 hours in slight CET). Most of patients, 488 (83.5%), were referred from another hospital, whereas the remaining cases came directly from the accident place. Traumatic mechanisms according to the previous categories were: occupant 145 (25%), pedestrian 112 (20%), motorbike 104 (18%), cyclist 2 (0.003%), labor 39 (7%), drop 154 (27%), sporting 7 (1%), aggression 10 (2%). Percentage of traffic accident was higher in patients with severe CET (74.6, 64, and 47% in severe moderate, and slight CET, respectively). The main lesions were: acute subdural hematoma, 72 (12.3%); cerebral contusion, 207 (35.4%); epidural hematoma, 88 (15%); normal computerized tomography/subarachnoid hemorrhage, 87 (14.8%); swelling, 17 (2.9%); diffuse axonal injury, 74 (12.6%); and the remaining, 39 (6.6%) had other lesions such as hydrocephalus fracture-sinking, etc. Mortality was 44.2, 12.2, and 3.7% respectively in severe, moderate, and slight CET. CONCLUSIONS: Data base may contribute to establish the prognosis of CET and to determine the efficacy of therapeutic procedures as well as that of diagnostic and investigational methods. PMID- 1410747 TI - [Regional blockage for arterial blood pressure control during placement of head holder in neurosurgery]. AB - OBJECTIVE: To achieve a hemodynamic stability in neurosurgery during placement of the craniostate, we compared the effects of blocking frontal and occipital nerves with supplementary doses of fentanyl with the effects observed after subcutaneous infiltration of craniostate fixation points. MATERIAL AND METHODS: We studied 34 patients with intracranial masses programmed for craniotomy who were randomly allocated into three groups. Group I received fentanyl 3-5 micrograms/kg, 5 minutes before implantation of craniostate; Group II was treated with subcutaneous infiltration of mepivacaine 2% at craniostate fixation points; and Group III underwent blockade of frontal and occipital nerves. Mean arterial blood pressure was measured at baseline, immediately before craniostate placement, and during the maximal rise induced after placement of the craniostate. RESULTS: Mean arterial blood after craniostate placement was significantly higher in Group I than in Group II (p < 0.01), and higher than in Group III (p < 0.05). CONCLUSIONS: Blockade of frontal and occipital nerves is a useful method for maintaining hemodynamic stability during craniostate placement in neurosurgical patients. PMID- 1410748 TI - [Comparative study in pediatric inhalation anesthesia. Clinical characteristics and anesthetic complications with halothane and isoflurane]. AB - OBJECTIVES: Comparative study of clinical characteristics and complications during induction, maintenance, and recovery in pediatric inhalational anesthesia between two commonly used fluoride agents (halothane and isoflurane). MATERIAL AND METHODS: We studied 66 children aged 1 month to 13 years undergoing general anesthesia for short lasting surgery who were divided into two groups of 33 patients each one: Isoflurane group and halothane group. Induction and maintenance anesthesia was performed with the corresponding inhalant agent. Parameters measured were duration of unconsciousness, time elapsed for intubation and recovery, heart rate, arterial blood pressure, and incidence of complications. RESULTS: Children anesthetized with isoflurane showed a shorter period of unconsciousness (1.55 +/- 0.11 min) than those anesthetized with halothane (1.91 +/- 0.12 min); whereas that the time required for intubation was significantly more prolonged (8.94 +/- 0.51 and 6.57 +/- 0.32 min, respectively). The incidence of complications was higher in the isoflurane group, mainly expressed as laryngeal spasm during the induction period. Both groups of patients showed a similar hemodynamic behaviour, although diastolic arterial pressure during maintenance anesthesia was significantly lower with isoflurane. Anesthesia recovery was faster and more predictable with isoflurane than with halothane. CONCLUSIONS: Anesthetic agent isoflurane is less appropriate than halothane for induction in pediatric anesthesia due to a high incidence of complications, specially laryngeal spasm. PMID- 1410749 TI - [Treatment of spasticity with intrathecal baclofen]. AB - INTRODUCTION: Severe spasticity, according to Lance's definition, is a manifestation of superior motoneurone injury syndrome which is characterized by increased stretching tonic reflexes, osteotendinous hyperreflexia, and release of propioceptive reflexes. Baclofen (a beta-4 chlorophenyl derived from gamma-amino butyric acid) was firstly administered by intradural route in humans by Penn and Kroin in 1985 for the treatment of severe spasticity of muscular and central origin. MATERIAL AND METHODS: We report the results obtained in eleven patients with severe spastic picture, six of medullar origin and five of central origin who were treated with intradural administration of baclofen using an implanted programmable continuous perfusion system (Synchromed 8611H). The age of patients ranged from 12 up to 58 years. Six were males and five females. The duration of the treatment ranged from a maximal period of 36 months to a minimal period of 12 months. The initial dose of baclofen varied from 50 micrograms/day to 144 micrograms/day. RESULTS: The better results were obtained in patients with spasticity of medullar origin. The most marked beneficial effects were the reduction of spasms elicited, or not, by external stimuli. In all cases the doses of baclofen had to be progressively increased, leading to a mean final dose of 235.6 micrograms/day, with a maximal dose of 480 micrograms/day and a minimal dose of 144 micrograms/day. CONCLUSIONS: Baclofen administered by intradural route is more effective than administered by orally and the required doses were lower. Intradural administration was effective even though the oral route was unsuccessful. PMID- 1410750 TI - [Maintenance of organ donor]. PMID- 1410751 TI - [Some Spanish contributions to anesthesiology at the end of the XIXth century]. AB - At the end of the XIXth century some original, although poorly known, Spanish contributions were made on the field of inhalational general anesthesia that are important for the history of our specialty in Spain. The purpose of this work is to report the Spanish contributions to inhalational general anesthesia made during the chronological period that coincides with the locus-regional anesthetic techniques grown after the appearance of cocaine in 1884. PMID- 1410752 TI - [Study of thyroid function in the organ donor during brain death]. AB - OBJECTIVE: To determine the thyroid function in organ donors undergoing cerebral death and evaluate the effects that these possible alterations may exert on the early function of renal graft. DEVELOPMENT: Prospective study. Hormonal analysis when: 1) the diagnosis of cerebral death was made and 2) before organ extraction. PATIENTS: Fifteen organ donors with cerebral death. Twenty-nine patients who received the kidneys of these donors. PLACE: Neurotraumatologic Unit at the University Hospital Marques de Valdecilla. Referring center. MEASUREMENTS AND RESULTS: All donors showed low T3 and T4 values. Values of T4 and IT4L were significantly lower during the second determination (p < 0.05). Eighty percent of donors showed increased T3r values. TSH was low in 73% of cases. Dopamine requirements in donors or the incidence of acute tubular necrosis in recipients were not significantly higher in donors with lowest T3 values. CONCLUSION: The hormonal picture observed in the donors of this study is more characteristic of a "ill euthyroid syndrome" than a real hypothyroidism. The low values of T3 in donors is not associated with higher requirements of inotropic agents, nor with a higher incidence of acute tubular necrosis in renal grafts. PMID- 1410753 TI - [Prophylaxis with dantrolene sodium in 2 patients with susceptibility to malignant hyperthermia]. AB - We report 2 patients programmed for elective surgery who were considered susceptible to develop the malignant hyperthermia syndrome. The first patient had two familiarly antecedents of death produced by postanesthetic malignant hyperthermia, whereas the second patient suffered a clinical picture compatible with this syndrome during tonsillectomy, although followed a favourable recovery. The preoperative study including measurement of muscular enzymes, isoenzymes, and muscular biopsy was normal. In both patients an intravenous prophylactic treatment with dantrolene 2.5 mg.kg1 was undertaken before surgery. The first patient underwent hysterectomy under intradural anesthesia with bupivacaine 0.5%. The second patient had a maxillary fracture which was treated with osteosynthesis under general anesthesia. During the intervention and the postoperative follow up, both patients were free of signs related to malignant hyperthermia. We conclude that prophylaxis with dantrolene is necessary in patients susceptible to develop the syndrome of malignant hyperthermia. PMID- 1410754 TI - [Local anesthesia of the knee for arthroscopic surgery. Our experience in 1,000 cases]. AB - We performed local anesthesia of the knee for arthroscopic surgery in 1,000 patients who were diagnosed of meniscopathy, chondropathy, or block of the knee. We established two anesthetic times. The first consisted of an intraarticular administration of 40 ml of a mixture containing bupivacaine 0.5%, lidocaine 0.5% or prilocaine 1%, and adrenaline 1:200,000. The second was extraarticular and consisted of a local infiltration at the sites of entrance of the arthroscope or instrumental material with lidocaine 0.5% or prilocaine 1%, with adrenaline 1:100,000. We kept a latency period of 10 to 15 min, time required for setting up the arthroscopic procedure. Ischemia was systematically avoided. With this technique the following surgical treatments were performed: meniscectomy, curettage of articular cartilage, synovectomy, plica sections, and extraction of free bodies. Tolerance to surgery was excellent in 32.3% cases, good in 46.5%, regular in 16%, and bad in 5.2%. In no cases more complex anesthetic techniques were undertaken. We conclude that the anesthetic technique used in this study is appropriate for arthroscopic surgery of the knee and allows to perform ambulatory surgery. The procedure is not useful in cases of ligament reconstruction, regional infection, and rupture of the articular capsula. Although the anesthetic technique is easy some factors should be considered before indication of the procedure such as a careful selection of the patient, skillfulness of the surgeon in performing the arthroscopy, and the accuracy of the preoperative diagnosis. PMID- 1410755 TI - [Efficacy of topical administration of lidocaine through a Malinckrodt Hi-Lo Jet tube in lessening cough during recovery from general anesthesia]. AB - To achieve tracheal anesthesia during intubation, an endotracheal tube was purposely designed. The tube had multiple laser-induced perforations in its lower portion produced that allowed administration of the local anesthetic in a pulverized form. We evaluated the efficacy of lidocaine 2% in preventing cough during recovery from general anesthesia. The goal of this study was to perform a topical anesthesia of the hypopharynx, larynx, and trachea. This attenuates the laryngeal reflex occurring during anesthesia recovery and therefore, prevents from potential complications. Sixteen patients ASA I-II underwent surgery with general anesthesia. They were prospectively studied following a randomized double blind protocol. The control group received saline infusion (n = 6) whereas the experimental group (n = 10) was treated with lidocaine. At the end of the anesthesia period, the presence of cough was treated with the test solution. In 90% of cases treated with lidocaine, cough disappeared in about 30 seconds and patients tolerated the endotracheal tube until extubation was performed. All patients who received saline solution presented cough until extubation. PMID- 1410756 TI - [Thrombosis of intrathoracic veins. A complication of venous catheterization for temporary hemodialysis]. AB - Venous thrombosis of large vessels is a common complication, generally asymptomatic, that may occur during central venous catheterization for temporal hemodialysis. We report 2 cases of intrathoracic venous thrombosis which were suspected because of the difficulties occurring during catheterization of a new venous approach during dialysis. Both cases were diagnosed by angiography. PMID- 1410757 TI - [Incidence of perioperative myocardial infarction in patients undergoing extracorporeal circulation for cardiac prosthesis implantation]. PMID- 1410758 TI - [Transfusional problems in oncologic surgery]. PMID- 1410759 TI - [Double episode of air pulmonary embolism]. PMID- 1410760 TI - [Polyneuropathy of the critical patient]. PMID- 1410761 TI - [Prolonged and deep neurologic depression after intravenous perfusion of midazolam]. PMID- 1410763 TI - [XXIVth National Congress of the Spanish Society of Cardiology. Valencia, 4-7 October 1992. Abstracts]. PMID- 1410762 TI - [Use of laryngeal mask for fiber optic bronchoscopy in a neonate with facial malformations]. PMID- 1410764 TI - Nitrobenzylthioinosine binding cooperativity in chromaffin tissue membranes. AB - The nucleoside transporter present in chromaffin tissue membranes has been studied by [3H]nitrobenzylthioinosine (NBTI) binding. This ligand presents a high affinity, with a Kd value of 2.1 +/- 0.2 nM and a Bmax of 1.7 +/- 0.2 pmol/mg protein. From the Scatchard and the semilogarithmic graphical representations a positive cooperativity was deduced, with a Hill coefficient of 1.7 +/- 0.4. In displacement studies of NBTI by the non labelled compound, the Hill coefficient was also higher than 1 (1.44 +/- 0.11) in the presence of ATP. This nucleotide seems necessary to maintain the number of high affinity binding sites. PMID- 1410765 TI - [Effect of the level of sexual receptivity on plasma estradiol and the ovulatory response during the postpartum period in the rabbit]. AB - The relation between plasma estradiol 17-beta mean levels (E2), sexual receptivity and ovulation response, as well as the evolution of E2 from day 29 of pregnancy until day 11 of postpartum in rabbits, was studied. The results suggest a direct relation between plasma E2 mean levels and high or low sexual receptivity. With a determined plasma E2 concentration was not able to predict sexual receptivity. The best ovulation response was obtained in rabbits of high or medium receptivity treated with 20 micrograms or 40 micrograms of GnRH. High plasma E2 mean concentrations were detected on day 1 and 9 postpartum. The evolution of E2 levels from day 29 of pregnancy until day 11 postpartum suggests that day 9 is the most favorable breeding day, when rabbits are to be submitted to a semi-intensive reproduction management. PMID- 1410766 TI - Potentiation by epidermal growth factor of the in vitro HCG stimulation of testicular steroidogenesis in hamsters. AB - Epidermal Growth Factor (EGF) has been reported to stimulate or inhibit steroidogenesis in murid Leydig cells depending on the experimental conditions used. In the present study, testicular fragments from an adult cricetid rodent, the Syrian hamster, were incubated with various doses of mouse EGF (0-2.0 micrograms/ml media), in the presence or absence of HCG (0-12.5 mlU/ml media). Although EGF alone did not affect in vitro testicular steroidogenesis, it significantly potentiated the HCG-induced elevation of the accumulation of testosterone and 17-hydroxyprogesterone in the media. In contrast, the effect of HCG on media progesterone concentration was not affected by EGF. Since in the Syrian hamster intracellular calcium loading functions as a gonadotropic stimulus, the present results could be a consequence of the EGF-induced increase in cellular calcium levels. PMID- 1410767 TI - Morphofunctional changes in gastrointestinal tract of rats due to cafeteria diet. AB - Female rats fed a cafeteria diet from birth developed obesity at 60 days of age and their stomach, small intestine and caecum were enlarged when compared with controls, i.e. these regions had greater food storage capacity. In spite of the enlargement, these regions had similar or reduced weight and linear density, which is seen as proof of reduced mechanical performances. Cafeteria diet produced increased glucose duodenal absorption in older animals unlike the typical reduction known in controls. Tryptophan absorption was maintained high in adulthood, compensating for the low structural nutritive properties of the cafeteria diet. The results are interpreted as an adaptation to the cafeteria diet effects and properties: the characteristic overeating of foodstuffs with greater energy density, lower mechanical requirements and lower structural nutritive value than pelleted chow. PMID- 1410768 TI - On the multiplicity of sugar transport systems in guinea pig jejunum. AB - A study has been made in everted sacs of guinea pig jejunum to see if the two transport systems of glucose analogues characterized at the brush border membrane vesicles are operative. The transport kinetics of D-galactose and alpha methylglucoside up to 80 mM concentrations has been studied, as well as the mutual inhibitions between them at low and high concentrations of the substrate and at different concentrations of the inhibitor. Low temperature (20 degrees C) inhibits galactose transport at 0.1 mM (70%) and 40 mM (78%) concentrations. A mass transfer coefficient, KD, somewhat higher for galactose than for alpha methylglucoside, was obtained when the transport component was abolished by phlorizin. The transport of D-galactose and alpha-methylglucoside seemed to be compatible with the function of one system shared by both substrates, which presents greater affinity for alpha-methylglucoside. The functional existence of two systems of active transport at the brush border of guinea pig was not evidenced in intestinal preparations of whole tissue, due perhaps to the effect of the unstirred water layers. However, differences in KD values and some results of the mutual inhibitions may suggest a second system. PMID- 1410769 TI - Conformational changes of S-1 related to its dissociation from actin. AB - The peptide pattern obtained after proteolysis of S-1 with trypsin was different in the absence or presence of anions. The affinity of tryptic and undigested S-1 for anions (CN-, SCN- or HCO3-) was different, as reflected by the altered values of Ki or Ka obtained from ATPase activity measurements. Anions CN-, SCN-, HCO3-, or PPi induced dissociation of actomyosin when added to acto-S-1 or acto-heavy meromyosin. Among nucleoside di- and triphosphates, only triphosphates were effective with regard to the dissociation. The results suggest the existence of a regulatory site of cationic nature on S-1, which might be involved in the dissociation of actin from myosin. PMID- 1410770 TI - A preliminary study on the action of genus Allium on thyroid 131iodide uptake in rats. PMID- 1410771 TI - [Photoperiod variations of various blood biochemistry constants in the rabbit]. AB - Biochemical blood parameters generally show fluctuations during the day. The aim of this study is to determine the variations of the following parameters: hemoglobin, glucose, triglycerides, ASAT, ALAT, urea and creatinine in New Zealand white (NZW) rabbits, kept under five different circadian rhythms (12/12, 14/10, 10/14, 16/8, 8/16, light/dark). These parameters were analyzed by using a reflection photometer (Reflotron). Most results are found within the physiological range for this species but there are significant differences among cycles. These findings could be explained by the dependence of the biochemical blood parameters on the light/dark cycle. It can be concluded that the most useful cycle to find fewer variations of the biochemical blood parameters in NZW rabbit is 12/12 light/dark cycle. PMID- 1410772 TI - [Focus on rehabilitation of the spinal cord injury patient--development and outlook]. PMID- 1410773 TI - [25 years Heidelberg Rehabilitation Center for Spinal Cord Injuries--retrospect and prospects]. AB - In the framework of a commemorative gathering and scientific symposium in November 1991, an account was given of the 25 years of service of the Rehabilitation Centre for Spinal Cord Injured Persons of the Heidelberg Orthopaedic University Hospital Foundation. Tribute was at the same time paid to the lifework of Kurt Lindemann, former director of the Orthopaedical University Hospital and rector magnificus of the Heidelberg Ruperto Carola University, in memory of the 25th anniversary of his death in 1966. Encouraged by the father of SCI rehabilitation Sir Ludwig Guttmann, of Stoke Mandevillehospital, England, Kurt Lindemann had taken the initiative for establishing this centre and prepared its opening in 1966. Comprising a clinical department, the Ludwig Guttmann House, and a department for vocational-social rehabilitation, the Kurt Lindemann House, the centre has since enabled provision of all measures required for comprehensive rehabilitation of spinal cord injured women, men and children--starting at the day of injury till full resettlement of this population in family, occupation, and society. Erected a quarter century ago, the centre has in the last two years been brought up to date architecturally and structurally; further measures for implementing the most recent state of the art in rehabilitating spinal cord injured patients lie ahead. PMID- 1410774 TI - [Clinical rehabilitation of the spinal cord injury patient--is the Guttmann concept still valid?]. AB - The focus of Guttmann's treatment concept had been to set up a comprehensive rehabilitation system, aimed not only at saving the life of a person with paraplegia or tetraplegia but at giving it meaning as well. Progress made in the fields of rescue services, anaesthesia, intensive medicine, in spinal surgery, neurourology and diagnostics (CT, MRI) as well as in pharmacology, have decisively enhanced the possibilities of clinical rehabilitation, and have in some respects entailed deviations from Guttmann's classical treatment principles. Moreover, the patient population has changed in profile in the course of time, due to better chances of survival also in high-level tetraplegia, greater numbers of higher-age SCI patients and of patients with non-traumatic SCI (tumours, metastases, infections). A higher life expectancy achieved by better possibilities as regards prevention and treatment of SCI-related complications, new challenges for the future emanate from age-related diseases occurring in addition to the spinal lesion. PMID- 1410775 TI - [Neuro-urology--development of a new focus in rehabilitation of the spinal cord injured patient]. AB - While preservation of renal function continues to be the primary objective in the urological care of spinal cord injured patients, new treatment principles have resulted in increased attention being given also to restoration of lost urinary continence, a goal shared by the patient as well. The fact that intermittent catheterization has stood the test also for the long-term management of micturition, as well as the development of effective medication for hyperreflective detrusor relaxation have resulted in a treatment concept that enables 70 percent of those treated to achieve dry intervals between catheterizations. Effective electromiction is today enabled by the sacral anterior root stimulator (Brindley), with continence ensured by sacral deafferentation performed at the same time; both measures have proved successful at medium term. Bladder augmentation is another operative measure for controlling detrusor hyperreflexia. Neurogenic urinary stress incontinence can be tackled successfully by implanting an hydraulic sphincter system (Scott). Both the advantages and the possible disadvantages or risks of these new management concepts are set out, dealing also with their indications. Successful treatment of erectile dysfunction is possible today, and inseminable sperma can be obtained in some 40 to 50 percent of the spinal cord injured patients. PMID- 1410776 TI - [Management of the spinal cord injured patient--hospital routine or principles of comprehensive rehabilitation?]. AB - Based on her own experience in the rehabilitation of spinal cord injured patients, the author describes the nursing service's self-concept and its development over the past 25 years, as well as changes in its working conditions inter alia entailed by technical advances. Requirements are posited, which are considered indispensable for comprehensive rehabilitation, specifically with regard to the aftercare necessary for the person with SCI in the domiciliary situation. PMID- 1410778 TI - [Between creativity and functional use--development and determination of the status of ergotherapy in rehabilitation of the spinal cord injured patient]. AB - In the 60s, Occupational Therapy (OT) with spinal cord injured patients had primarily been based on manual activities, aimed at improving functional levels. Gradually, attainment of the highest possible level of independence became a central emphasis of OT care. While creative development of the patient seemed to conflict with this foremost objective of independence, practical experience in the meantime has taught that creative activity can be an avenue toward independence. Also, the OT regimen for SCI patients has for several years now been extended to include computer-based technology for functional treatment as well as prevocational measures. PMID- 1410777 TI - [Integration of patient exercise/physical therapy in the rehabilitation team]. AB - Described is the position of physiotherapy in the rehabilitation of persons with spinal cord injury, starting out on the assumption that physiotherapy lays the foundations for functional rehabilitation, enabling the other disciplines to build up on. Ideally, the treatment approach is not confined to a single concept, but several treatment modalities should equally be available. Physiotherapy must be integrated into the overall team approach. This can only be achieved on the basis of mutual respect, as well as physiotherapy staff continuity which enables broad knowledge and experience to be built by physiotherapists. PMID- 1410779 TI - [Responsibilities of clinical psychology in rehabilitation of patients with severe physical handicaps]. AB - Rehabilitation is a process intended to lead from disablement to enablement. This process must begin at the very onset of an impairment, with close cooperation of the rehabilitee with all the specialties involved, as well as among these specialties, being an indispensable prerequisite. Clinical psychology is one of these specialties, its primary emphases are diagnostics, counselling, therapy, research, staff training and further education, as well as organizational, operational and institutional counselling. To take part in shaping a more humane world is a task of psychology in research, theory, and practice. PMID- 1410780 TI - [...and after the clinic? Reflections on domestic-familial rehabilitation and management of the spinal cord injured patient]. AB - Both from a personal and professional perspective, considerations are presented concerning the domiciliary-familial rehabilitation of persons with spinal cord injury. The field of tension present within the living community affected by the disability (parents/children, partners, children/parents) is examined, the various specific strains, physical, mental, social-societal, are outlined. The problems entailed as regards autonomy/dependence, intimateness/distantness, lover, mother/father, and avoiding/facing conflict, are analyzed, and possible solutions suggested. PMID- 1410781 TI - [2.7 million unemployed--nonetheless occupational rehabilitation of patients with severe physical handicaps?]. AB - The concept of rehabilitation initially is defined as it is understood in the Federal Republic of Germany today. The potential opportunities and risks inherent in an outcome-oriented notion of rehabilitation are set out in light of its historical development. The reasons for unemployment among severely disabled persons are analyzed from various perspectives, dealing furthermore with the manner the vocational rehabilitation system is responding. Also mentioned are the difficulties where our system is working only to a limited degree, as well as the consequences this entails. Further, reasons are given to substantiate that the rehabilitation of severely disabled people remains an important and meaningful task in our country notwithstanding current unemployment. PMID- 1410782 TI - [Progress, detours, errors--social legislative aspects of the development of rehabilitation]. AB - Any person threatened by the onset of disability has a right to the assistance needed to integrate in work, career, and society (section 10, Book 1 of the Social Code). A highly sophisticated system of legal provisions and pursuant administrative competencies, eligibility requirements and benefit provision modalities seeks to fulfill this entitlement. The system of available services is subject to on-going development, with adjustments necessary in response both to medical advances and labour market or technological developments. The adjustment process is limited by the economic resources available, which may restrict the scope of what is considered feasible regardless of what might be possible or desirable. To avoid becoming entangled in the "jungle" of its own system of competencies and eligibilities, a rehabilitee-centred rehabilitation approach must seek to make even better use of the manifold opportunities of rehabilitation legislation in light of the individual case at hand and based on professional cooperation. Any further development of rehabilitation legislation will moreover have to pay attention to those persons for whom occupational integration is no longer, or not yet, possible, in order to face up to future social challenges. PMID- 1410783 TI - [Handicap--negative variant of the "normal"--or else? Comments on the problem of attitude to deficits in rehabilitation and ethical principles]. AB - Uncertainty as to what exactly is comprised by disability is quite frequently encountered not only in the general public but also among rehabilitation workers. The "normal" is deemed the desirable, and "disability" turns into its negative counterpart. Attention is focussing on the deficits that appear on measuring and comparing. A critical discussion of deficit orientation in education and care of disabled persons is needed. Isolated identification of and attendance to deviations must be overcome by interdisciplinarity and team work, in order to pay due respect to the person as a whole, to his or her social and personal identity. Also, fundamental issues of the current ethics discussion in special education arise in this context. Shown on the example of J. J. Rousseau, reference to philosophical or educational "authorities" may turn out to be misguided. PMID- 1410784 TI - [25 years rehabilitation. Questions--answers, unanswered questions--retrospective answers]. AB - Starting out from the 10th World Congress of the International Society for Rehabilitation of the Disabled, held 1966 in Wiesbaden on the subject of "Industrial Society and Rehabilitation", social-legislational developments are out-lined, among them the 1971 accident insurance coverage for pupils, the 1974 rehabilitation harmonization act, and the 1975 extension of social insurance coverage to disabled persons working in workshops for the disabled; problems yet unsolved in the structured system of social protection are pointed out. The problem of "early rehabilitation", still to a very great extent unresolved, is dealt with in the context of the present distinction between "acute medicine" und "rehabilitation" facilities. In rehabilitation of persons with chronic mental illness, numerous models have been developed; a generally accepted, and available approach however has not emerged so far. For ensuring care quality and continuity, the urgent need for community-based availability of the "rehabilitation team" is underlined, and interdisciplinary further education efforts are demanded for all professions in the team, both in facility- and community-based service delivery. PMID- 1410785 TI - [Combined vocational education and industrial management--presentation of a cooperative project for improved integration of adolescents with learning handicaps]. AB - Major structural labour market changes, i.e. dramatic losses in job opportunities for unskilled labour and continually rising levels of job requirements facing skilled workers on the one hand and an increasing demand for skilled workers on the other, are entailing enhanced job opportunities for disadvantaged societal groups, at the same time however also increasing the occupational risk of these populations, among them the learning disabled. The vocational training centres having for more than a decade been gaining experience in the vocational and social rehabilitation of this latter group, the project outlined is intended to make even better use of their potential. The main objectives of the project are: 1. optimizing the vocational training centres' range of placement-focussed measures by: intensifying industrial training periods, coordinated "start up" support on occupational entry, post-placement services; 2. transfer of the vocational training centres' technical knowledge and experience into industry based training by: follow-along support services ("ausbildungsbegleitende Hilfen"), workshops on the initial vocational training of learning disabled young adults, and other forms of cooperation. Apart from reaching the goals outlined, the project is expected to give new impulse to the day-to-day practice of the vocational training centres as well as to generate even greater networking of the centres with their industrial environments. PMID- 1410786 TI - [The favorable effect of group housing on the occupational performance of psychiatrically handicapped patients]. AB - A cohort of psychiatrically disabled persons was investigated to determine whether work performance changed after entry into a residential commune. Both before and after entering the commune, a differentiated spectrum of work opportunities graded according to performance requirements had been available. A clear enhancement of work performance was found following entry into the residential commune. In a further step, variables associated with above- or below average increases in work performance were identified. On the whole, the results underscore the value of residential communes in the vocational rehabilitation of psychiatrically disabled persons. PMID- 1410787 TI - [Changes in health status and attitude due to sports with rheumatic disease patients]. AB - A six-months sports programme had been implemented to analyze the impact of movement, play and sports on the physical situation of persons having rheumatism, their mental well-being and attitudes towards sporting activities. 41 patients participated in the programme, attending training sessions in a fitness studio once a week. The sports programme contained general endurance training, functional and strengthening exercises, elements of gymnastics and play, as well as relaxation techniques. The following assessment tools were used: Measurement of Patient Outcome (MOPO) scales, sports questionnaire, and the STEP test. It was found that participants' health status, both physical and mental, had been influenced in a positive manner, with proof being provided of reduced levels of anxiety, depression, and pain. Moreover, attitudinal changes toward sports appear to have resulted, suggesting persistent motivation to engage in sporting activity. PMID- 1410788 TI - Biosynthesis and distribution of N-carboxyalkyl amino acids (opines) in bacteria. PMID- 1410789 TI - Transcriptional mapping of the promoter of the aminoglycoside acetyltransferase gene (aacC9) of neomycin-producing Micromonospora chalcea. AB - We have studied the promoter of the gene encoding aminoglycoside acetyltransferase (aacC9) in neomycin-producing Micromonospora chalcea. S1 nuclease mapping showed that the transcription initiation point of this gene is at the translation start point, with no evidence of a conventional ribosome binding site. The aac of paromycin-producing Streptomyces rimosus forma paromomycinus shows the same characteristic; there is no homology in the promoter regions of the two genes, whereas the coding sequences are very similar. PMID- 1410790 TI - Structure/function relationships in the Escherichia coli mannitol permease: identification of regions important for membrane insertion, substrate binding and oligomerization. AB - The Escherichia coli mannitol permease (EIIMtl) of the phosphoenolpyruvate dependent phosphotransferase system is a 68-kDa membrane protein that carries out the concomitant transport and phosphorylation of D-mannitol. Previous studies indicated that there are ca. 6 membrane-spanning helices within the N-terminal half of the protein, while the hydrophilic C-terminal half was shown to be exposed in the cytoplasm. In the present study, an analysis of C-terminally truncated EIIMtl mutants showed that proteins from which only the cytoplasmic domain has been deleted were present in the membrane at > or = 50% the amount of the intact protein. However, deletion proteins smaller than ca. 34 kDa were present in the membrane at only about 20% the amount of the intact protein. We also constructed a plasmid that encodes the first 43 amino acid residues of ELLMtl fused to residues 378 to 637 (the C-terminal domain). The corresponding protein was associated with the cytoplasmic membrane. These results show that the first 43 amino acid residues of the N terminus are sufficient for membrane localization, although the region comprising the last 2 membrane-spanning helices appears to be important for maximum stability and/or efficient membrane insertion of the complete N-terminal domain. Further studies of these deletion proteins showed that binding of mannitol to the permease occurs even if the entire cytoplasmic domain is absent, but is abolished if the last putative membrane spanning region is removed. Finally, regions of the protein within the membrane bound domain were identified that influence the oligomerization state of the protein. These results further define domains of this multifunctional transport protein that are important for membrane insertion, stability, substrate binding and oligomerization. PMID- 1410791 TI - Bacteriocin-like activity of Bacteroides fragilis group isolated from marmosets. AB - The ability of strains of the B. fragilis group, isolated from the oral cavity and intestine of marmosets, to produce bacteriorin-like substances in solid medium, in terms of auto-, iso- and heteroantagonism, was evaluated. Antagonistic activity was exhibited by 52% of the intestinal strains, 3 of which showed autoantagonistic activity. Three out of 9 oral strains isolated, tested against themselves, showed simultaneous isoantagonism to 4 indicator strains; but not autoantagonism. The same 9 oral strains, when tested against 16 reference strains, revealed interspecific activity only against 2 Gram-positive microorganisms. Higher activity, evaluated by the size of the inhibition halo, was observed in BHI-S agar, and greatest inhibition was obtained after 72 h of incubation. PMID- 1410792 TI - Catabolic pools in Escherichia coli. AB - Methods are described for measuring soluble pool magnitudes in steady-state or exponentially growing cultures, and for distinguishing between anabolic, catabolic and total metabolic pools within cells. These methods were applied to the measurement of pool magnitudes for several amino acids and other precursors in Escherichia coli THU. Our results support the independence of the magnitudes of total metabolic pools and growth rate in steady-state cultures. Our results also show that the total metabolic pool size is much larger than previously published estimates, which failed to include the contribution of catabolic pools. The average value of the total soluble material in exponential-phase cells is estimated to be 8 to 9% of the cell dry mass; pool values could be almost twice as large during midcycle because of the known increase in the magnitudes of protein and RNA precursor pool during the cell cycle. PMID- 1410793 TI - Evaluation of a chemiluminescent DNA probe assay for the rapid confirmation of Listeria monocytogenes. AB - A Listeria monocytogenes-specific, acridinium-ester-labelled DNA probe was evaluated in a chemiluminescent homogeneous protection assay (HPA) for the rapid confirmation of suspect L. monocytogenes colonies from blood agar plates. The HPA uses an acridinium-ester-labelled chemiluminescent DNA probe in a free-solution hybridization format. After the DNA probe hybridized with the target ribosomal RNA, the acridinium label on the unhybridized probe was inactivated by a chemical differential hydrolysis step. Formation of a hybrid between probe and target was detected in a luminometer after the addition of a detection reagent. The assay can be completed in 30 to 45 min and allows for simultaneous processing of several (50-100) samples. The probe showed 100% sensitivity and 100% specificity for L. monocytogenes when evaluated in the HPA against L. monocytogenes, other Listeria species and other Gram-positive bacteria. The lower detection limit of the HPA was between 10(4) and 10(5) cells. In an evaluation with 296 bacterial colonies isolated from food, the HPA colony confirmation showed 100% agreement with conventional biochemical characterization. HPA will be useful for the rapid confirmation of L. monocytogenes isolated from food and clinical specimens. PMID- 1410794 TI - Contribution of high-performance liquid chromatography to the identification of some Corynebacterium species by comparison of their corynomycolic acid patterns. AB - Reverse-phase high-performance liquid chromatography of corynomycolic acids provided a specific pattern for each Corynebacterium species studied. These data suggest that a fast and reproducible procedure is now available for bacteriological identification at the genus and at the species level of corynomycolic-acid-containing bacteria. Mass spectrometry analysis of post-column collected fractions provided the order of elution of some corynomycolic acids and isomers and showed the high specificity of the chromatographic assay which could be used for the routine bacteriological identification of some species belonging to the genus Corynebacterium. PMID- 1410795 TI - Heterogeneity in restriction patterns of Gardnerella vaginalis isolates from individuals with bacterial vaginosis. AB - This study was undertaken to resolve the genetic make up of Gardnerella vaginalis present in bacterial vaginosis (BV). DNA from several G. vaginalis isolates from within and between individual BV patients were compared by BamHI, ClaI and EcoRI restriction endonuclease analysis (REA) followed by a restriction fragment length polymorphism (RFLP) study, utilizing a 5.7-kb BamHI G. vaginalis ATCC14018 DNA probe. Four G. vaginalis isolates from one patient (GVP-062) were composed of 3 different biotypes (biotypes 3, 5 and 8), and while the REA mirrored the biotype, in RFLP studies at least 3 isolates had DNA fragments in common. All of the isolates from 2 other patients (GVP-063 and GVP-072) represented a single biotype (biotype 2), but under REA and in RFLP studies, the isolates GVP-063 differed from GVP-072. An opposite case existed with the isolates GVP-072 (biotype 2) and GVP-065 (biotype 5), which appeared similar under REA and in RFLP studies. Finally, reisolates after 8 weeks (GVP-080) from a BV patient (isolates GVP-065) representing the same biotype (biotype 5) differed under REA and in RFLP studies. Thus, lacking any unique DNA fingerprint, G. vaginalis occurring in BV represents a (genetically) mixed population. PMID- 1410797 TI - Evaluation of synthetic pseudo cord-factor-like glycolipids for the serodiagnosis of tuberculosis. AB - A number of glycolipids were evaluated in an ELISA test for their serodiagnostic usefulness in tuberculosis. One hundred and twelve (112) sera belonging to bacteriologically confirmed TB patients, patients with pathologies other than tuberculosis and healthy individuals were examined against several synthetic "mirror" pseudo cord factors (analogues of trehalose-6,6'-dimycolate or TDM) using natural cord factor and another recently described natural glycolipid (SL IV) of Mycobacterium tuberculosis as control antigens. Analysis of the results shows that all synthetic "mirror" pseudo cord factors, except one with a short 8 carbon chain, were better recognized by the sera of tuberculosis patients than natural cord factor, with sensitivity and specificity values in the ELISA test similar to those reported for M. tuberculosis species-specific SL-IV. Of all antigens tested in this study, BDA. TDA, a bis(N,N-dioctadecylamide) of "trehalose dicarboxylic acid", [(alpha-D-glucopyranosyluronic acid) (alpha-D glucopyranosiduranic acid)], showed the highest serodiagnostic discriminating power (93% sensitivity and specificity). We postulate that either these artificial molecules are cross-reactants of similarly structured native glycolipids of M. tuberculosis or that they bear closer resemblance to actual phagosome-lysosome-modified antigens than to native mycobacterial ones. PMID- 1410796 TI - Novobiocin, brilliant green, glycerol, lactose agar: a new medium for the isolation of Salmonella strains. AB - We describe a medium, novobiocin, brilliant green, glycerol, lactose (NBGL) agar, for the routine isolation of Salmonella strains from stool samples. The NBGL agar principle involved the use of the antisaprophytic effect of brilliant green and novobiocin. Glycerol and lactose were added in order to distinguish between Citrobacter and Salmonella. NBGL was used in parallel with salmonella-shigella (SS) and Hektoen (H) agar for culturing 2,853 stool samples, of which 184 were confirmed to be salmonellae. NBGL showed a high sensitivity: 94% in direct plating compared to 74% (p < 10(-3)) and 65% (p < 10(-5)) for H and SS, respectively, and 96% in enrichment broth plating vs. 83% (p < 10(-4)) and 86% (p < 10(-3)), respectively, for H and SS. In direct plating using NBGL, 95% of black centred colonies were confirmed to be salmonellae (vs. 31% and 36%, H and SS). In enrichment plating using NBGL, this figure was 82% (vs. 26% and 28%). The results suggest that NBGL agar is advantageous for the isolation of non-Typhi H2S+ salmonellae. PMID- 1410798 TI - Identification of sulpholipid I by thin-layer chromatography in the rapid identification of Mycobacterium tuberculosis. AB - A simple, rapid and reliable thin-layer chromatography method for the detection of the 2,3,6,6'-tetraacyl trehalose-2'-sulphate (sulpholipid I) from Mycobacterium tuberculosis was described. The method was found to be satisfactory as an aid in the rapid identification of M. tuberculosis in clinical laboratories. PMID- 1410799 TI - Relation between the number of sperms to be deposited and pregnancy rate in tubal insemination in rabbits. AB - Pregnancy rate of tubal insemination with semen diluted to concentrations of x10(0) to x10(7) was studied in rabbits. The animals were laparotomized under general anesthesia, and 0.05 ml of diluted semen was injected with a glass capillary from the tubal fimbria into the oviduct. The semen was obtained from mature male rabbits by means of an artificial vagina and diluted to concentrations between x10(0) and x10(7). One hour after the insemination, ovulation was induced by administration of hCG. Six experimental groups were set up according to the semen concentrations. In the x10(0), x10(2), x10(4), and x10(7) groups, newborn rabbits were obtained. The best pregnancy rate was obtained with the x10(2) groups, in which 10(5) level of sperms were deposited. The newborn rabbits were normal not only morphologically, functionally, but also in chromosomal examination. The results suggested that tubal insemination with a small number of sperms could be applied in sterility due to oligospermia in human. PMID- 1410800 TI - Long term monitoring of immunoreactive endothelin-1 and endothelin-3 in ventricular cerebrospinal fluid, plasma, and 24-h urine of patients with subarachnoid hemorrhage. AB - Endothelins (ETs), peptides that were originally isolated from endothelial cells, have extremely potent and long-lasting vasoconstricting effects on cerebral vessels in vitro and in vivo. Observations that astrocytes produce these peptides and that their ET production can be stimulated, e.g. by thrombin, and potentiated via a self-enhancing autoregulatory mechanism may have shed new light upon the pathogenesis of cerebrovasospasm (CVS). ETs are present at low levels in normal human cerebrospinal fluid (CSF). Few and contradictory reports exist on ET levels in subarachnoid hemorrhage (SAH)-associated CVS. We monitored ventricular CSF, plasma, and 24-h urine levels of immunoreactive endothelin-1 (ET-1) and endothelin-3 (ET-3) in seven patients with SAH, who did (five) or did not (two) develop CVS in the course of their disease, as well as in two patients with different conditions (acoustic neuroma/postoperative meningitis; hydro /hematocephalus) over 7-19 days. A distinct peak of both ET-1 and ET-3 in CSF of patients with SAH coincided with clinically documented signs of CVS and was absent in CSF of patients with SAH but no CVS. CSF levels of ET-1 and ET-3 displayed a striking parallelism in all subjects. Plasma ET-1 levels were essentially in the normal range. ET-3 was not detectable in plasma under our assay conditions. The excretion profiles of ET-1 and ET-3 in 24-h urine revealed again a predominantly parallel behavior of the two peptides. Interestingly, patients with high ET levels in CSF showed simultaneous peaks in urinary ET excretion, expressed as nanograms per gram of creatinine. Our findings support an association of ETs with the pathogenic events following SAH. The well-documented effects of these peptides on cerebral vessels suggest they are mediators rather than markers of disease. PMID- 1410801 TI - Hemodynamic effects following intraperitoneal infusion of pancreatic ascites fluid. AB - Severe necrotizing pancreatitis is accompanied by release of hemorrhagic ascites fluid (HAF), which is thought to be related to the occurrence and frequency of cardiocirculatory and pulmonary failure as a consequence of acute pancreatitis. The purpose of this study was to evaluate the role of HAF due to these systemic complications. Experiments were performed in 25 pigs (mean b.wt. 22 +/- 1 kg) under general anesthesia and mechanical ventilation. The animals received 50 ml/kg b.wt. i.p. of either physiologic saline solution (control CO, n = 9) or hemorrhagic ascites fluid (HAF, n = 16). HAF was obtained from 16 pigs with pancreatitis induced by intraductal infusion of bile salt. Eight animals in the HAF group were pretreated with indomethacin (10 mg/kg i.v. INDO/HAF). All animals were followed up for 6 h. Mean arterial pressure, cardiac output, and stroke volume fell significantly in the HAF (-25%, -27%, -27%) and in the INDO/HAF groups (-24%, -20%, -17%) as compared with controls (-6%, -6%, -6%). Also, left ventricular end-diastolic pressure (LVEDP) decreased by 52% and 48% in both HAF recipient groups, whereas LVEDP was unchanged in the control group. Myocardial contractility (Vmax) remained unaltered in all experimental groups. No significant differences in gas exchange and lung dry/wet weight ratio were observed. Lipase and PGI2 of the unpretreated HAF group rised to 203% and 198% in arterial blood at 6 h compared with unaltered levels in the control group. No increase of prostanoid concentrations was detected in the indomethacin-pretreated group, whereas lipase increase by a comparable extent as in the HAF group. We conclude that the early consequences of HAF are mainly characterized by systemic hypotension due to hypovolemia. PMID- 1410802 TI - Increase of S-(1,2-dicarboxyethyl)glutathione in regenerating rat liver. AB - Changes in the level of S-(1,2-dicarboxyethyl)glutathione (DCE-GS) with time were determined during regeneration of rat liver after partial hepatectomy. The DCE-GS level increased in regenerating rat liver, reaching a maximum level (4.7-fold) on day 2 and reverted to the normal level in 1 week. During the liver regeneration process, the activity of DCE-GS-synthesizing enzyme in the liver retained its control level, while the level of glutathione--a substrate of the enzyme in the liver--fluctuated in parallel with that of DCE-GS. PMID- 1410803 TI - Changes in membrane-bound hydrolases by metronidazole in rat renal brush border. AB - The antiprotozoal drug metronidazole, when administered orally at a dose level of 100 mg/kg body wt. daily for 7 days to rats, brought about significant elevation of renal brush-border-membrane-bound hydrolytic enzymes, such as alkaline phosphatase, maltase, sucrase, and leucine aminopeptidase (LAP). Kinetic analysis of the enzymes (substrate saturation) indicated that the drug produced an increase in the maximum of apparent initial enzyme velocity (Vmax), while the substrate affinity constant (Km) remained unaltered. These changes were not recovered to the normal level even after the drug regimen was stopped and the animals were allowed to recover for a period of 7 days. Lipid analysis of brush border membrane (BBM) revealed a significant elevation in the cholesterol, phospholipid, and ganglioside levels, while no marked change was recorded in triglyceride, free fatty acid and plasmalogen. Study of the temperature-dependent parameters of the enzymes showed that metronidazole induced a shift in the transition temperature (To) in LAP with nearly total reversibility in the recovery group. No such change was seen in the other enzymes. However, there also was a lowering in the energy of activation (Ea) below To, which returned to normal after the treatment was withdrawn. PMID- 1410804 TI - Recently described scrapie-like encephalopathies of animals: case definitions. AB - Since 1986, naturally occurring scrapie-like encephalopathies have been described in the United Kingdom in domestic cattle, in five species of captive exotic bovids and in domestic cats. The disease in domestic cattle, bovine spongiform encephalopathy, has been characterised by all currently available diagnostic criteria as a transmissible spongiform encephalopathy or 'prion' disease, and has been shown to have a dietary origin. The pathology in the other species is also entirely consistent with the scrapie-like diseases. The contemporaneous occurrence in the UK of such disease in these species suggests a close epidemiological association. The diagnostic criteria of the scrapie-like encephalopathies of animals are reviewed in the light of experience with the recent extension of their natural host range. PMID- 1410805 TI - Clinical equine dysautonomia and autonomic neuron damage. AB - Damage to the neurons of selected autonomic ganglia was quantified in relation to the severity of the clinical signs shown in acute, subacute and chronic cases of dysautonomia (grass sickness). No connection between the clinical severity of acute or subacute dysautonomia and the amount of neuronal damage in the superior cervical, stellate and coeliaco-mesenteric ganglia could be demonstrated. However, a higher proportion of normal neurons were found in chronic cases. Jejunal submucosal neuronal damage was correlated with clinical severity but further work is required to confirm this finding and to establish how widespread the alimentary neuronal lesions are in dysautonomia of different severities. PMID- 1410806 TI - Improved isolation of rinderpest virus in transformed bovine T lymphoblast cell lines. AB - Bovine T lymphoblast cell lines transformed by the protozoan Theileria parva were compared with bovine kidney (BK) and Vero cells for their ability to isolate various strains of rinderpest virus from tissues and infected secretions. All of the strains of rinderpest virus that were tested, including attenuated cell culture, caprinised and lapinised vaccines, and both mild and virulent pathogenic strains, readily induced syncytial cytopathic effect (cpe) in T lymphoblasts. The cpe could often be detected within one day of inoculation of lymphoblasts, whereas it took three to 14 days to appear in Vero and BK cells. Using lymphoblasts it was possible to reisolate rinderpest virus from nine of 42 swabs collected from three cattle experimentally infected with an isolate from a recent outbreak of mild disease whereas the same swabs yielded only one reisolate on BK cells. It was also possible using the lymphoblasts to detect infectious virus in the ocular, nasal and oral secretions of goats and rabbits infected with caprinised and lapinised virus, respectively. Peste des petits ruminants virus appeared to grow as rapidly as rinderpest virus in the lymphoblasts whereas canine distemper virus readily induced cpe on first passage but less readily on subsequent passage. Measles virus induced relatively little cpe when inoculated into lymphoblasts and did not appear to passage in these cells. The lymphoblasts are easy to maintain in culture and since they rapidly recovered 11 isolates from 37 diagnostic samples could prove useful in laboratories carrying out rinderpest diagnosis. PMID- 1410807 TI - Anaerobic microflora associated with the pars oesophagea of the pig. AB - In healthy pigs aged one to 35 days significant populations of microorganisms (5.5 to 6.9 log10 viable count cm-2 of the tissue) were found, by strict anaerobic techniques, to adhere to the pars oesophagea. The genera of anaerobes which were isolated included Actinomyces, Bifidobacterium, Clostridium, Lactobacillus, Peptostreptococcus, Streptococcus and Veillonella and facultative anaerobes included Escherichia, Klebsiella, Staphylococcus, Streptococcus and yeasts. The microbial population adhering to the pars oesophagea varied little from birth till after weaning and Lactobacillus, Clostridium and Eubacterium predominated. There were generally small numbers of facultatively anaerobic microorganisms in the pars oesophagea of healthy sucking or weaned pigs but large numbers of anaerobes, particularly Lactobacillus. In the pars oesophagea of sucking and weaned pigs with diarrhoea, large numbers of facultative anaerobes were frequent but Lactobacillus were also present in large numbers. PMID- 1410808 TI - Bracken poisoning and enzootic haematuria in cattle in China. AB - Acute bracken poisoning and enzootic haematuria are believed to have occurred in cattle in China for a long time. It is only in the past 10 years, however, that these diseases associated with the consumption of bracken ferns have been studied in detail and this paper reviews these recent studies. Based on a large scale survey, both conditions were found to be serious problems with a wide geographical distribution, especially in the mountainous regions of southwest China. Epidemiological and experimental work revealed that two species of bracken ferns, Pteridium aquilinum and Pteridium revolutum, were associated with these diseases, but the latter seems more important in China. PMID- 1410810 TI - Changes in the spontaneous and evoked electrical activity in the brain of hens during stunning with 30 per cent carbon dioxide in argon with 5 per cent residual oxygen. AB - Changes in the somatosensory evoked potentials (SEPs) and spontaneous electroencephalogram (EEG) in hens were investigated during stunning with a mixture of 30 per cent carbon dioxide in argon with 5 per cent residual oxygen. The results showed that the SEPs were lost on average in 17 seconds (maximum 28 seconds), which is similar to the 19 seconds (maximum 32 seconds) reported while stunning hens with a mixture of 30 per cent carbon dioxide in argon with 2 per cent residual oxygen. The spontaneous EEG showed suppression and a quiescent phase at 14 and 58 seconds, respectively. It is concluded that a mixture of 30 per cent carbon dioxide in argon with 2 per cent residual oxygen would be ideally suited for batch stunning chickens and any inadvertent increase in the residual oxygen level up to 5 per cent in the stunning atmosphere would not lead to inadequate stunning or recovery of consciousness before neck cutting. PMID- 1410809 TI - Effects of clinically occurring chronic lameness in sheep on the concentrations of plasma noradrenaline and adrenaline. AB - Plasma adrenaline (AD) and noradrenaline (NA) concentrations were measured by high performance liquid chromatography with electrochemical detection in blood samples from control and lame sheep. The lame sheep suffered from naturally occurring foot rot and showed behavioural characteristics normally associated with chronic pain. The lame sheep were scored both for impairment of gait and pathology of the foot and divided into mild and severely affected groups. Both the mildly and severely lame group showed a significant increase in plasma AD and plasma NA which tended to persist even after clinical resolution of the condition. The measurement of plasma AD and NA may provide information which can be used to assess animals experiencing chronic pain, when taken in conjunction with other parameters, such as nociceptive thresholds and plasma hormone levels. PMID- 1410811 TI - Administration of levothyroxine to euthyroid dogs does not affect echocardiographic and electrocardiographic measurements. AB - The effects of a replacement dose of levothyroxine on electrocardiographic and echocardiographic parameters in euthyroid dogs were examined. Two-dimensional guided M-mode echocardiograms and electrocardiograms were obtained before and after administration of levothyroxine (0.5 mg m-2 twice a day) to 10 euthyroid dogs for a period of eight weeks; four untreated dogs acted as controls. The resting serum total thyroxine concentration was significantly increased in treated dogs during weeks 4 to 8. There were no significant differences in any of the echocardiographic or electrocardiographic measurements resulting from treatment. PMID- 1410812 TI - Comparative immunoelectrophoretic analysis of Echinococcus granulosus, Taenia hydatigena and Taenia pisiformis cyst fluid antigens by hyperimmune rabbit sera. AB - Cyst fluid antigens of Echinococcus granulosus, Taenia hydatigena and T pisiformis were examined by electrophoresis using homologous and heterologous hyperimmune rabbit sera to these antigens. While arc 5 forming antibodies were identified in sera from rabbits immunised with E granulosus and T hydatigena cyst fluids, antibodies responsible for forming precipitating antigen B band were detected in rabbit antisera to E granulosus, T hydatigena and T pisiformis antigens. T hydatigena cyst fluid appears to contain antigen similar to E granulosus antigen 5 and probably antigen B while T pisiformis cyst fluid has mainly an antigen close to hydatid antigen B. PMID- 1410813 TI - Effects of nicarbazin on sugar intestinal absorption in rabbits. AB - Nicarbazin is an anticoccidial drug, used mainly in birds, which can also be used in rabbits. It has been shown to produce several effects, such as inhibition of growth and feed efficiency in poultry. The aim of the present work was to determine whether nicarbazin alters intestinal absorption of sugar. Results obtained show that nicarbazin decreases D-galactose accumulation in the jejunal tissue and increases mucosal to serosal transepithelial fluxes of this sugar, in both cases in a dose-dependent way. Furthermore, nicarbazin seems not to modify the sugar diffusion across the intestinal epithelium. The drug also stimulates the sugar uptake in brush border and basolateral membrane vesicles. The results suggest that in rabbits nicarbazin increases sugar intestinal absorption mediated by carriers. PMID- 1410814 TI - Indirect myosin immunocytochemistry for the identification of fibre types in equine skeletal muscle. AB - The histochemical ATPase method for muscle fibre typing was first described by Brooke and Kaiser in 1970. However, problems have been found with the subdivision of type II fibres using this technique. To determine whether indirect myosin immunocytochemistry using anti-slow (5-4D), anti-fast (1A10) and anti-fast red (5 2B) monoclonal antibodies with cross reactivity for type I, II and IIa fibres, respectively, in a number of species, could identify three fibre types in equine skeletal muscle, data on fibre type composition and fibre size obtained using the two different techniques were compared. Results indicate that different myosin heavy chains can coexist in single equine muscle fibres. Type I and type II fibres were identified by immunocytochemistry, but subdivision of type II fibres was not possible. Although the percentage of type I and type II fibres was not significantly different for the two techniques, a few fibres reacted with both the 1A10 and 5-4D antibodies. PMID- 1410815 TI - Plasma 1,25-dihydroxyvitamin D, insulin-like growth factor-1, calcium, magnesium and phosphorus concentrations in pregnant beef cows and calves from a herd with a known history of congenital joint laxity and dwarfism. AB - An investigation was undertaken to ascertain the possibility of a relationship between calcium, inorganic phosphorus, magnesium, 1,25-dihydroxyvitamin D [1,25(OH)2D], and insulin-like growth factor-1 (IGF-1) concentrations in blood plasma and occurrence of congenital joint laxity and dwarfism (CJLD) in young cattle. Pregnant cows were fed hay (30 cows) or grass silage (122 cows) during winter months (October 15 to calving in March). Blood samples were taken from cows on seven occasions during the experiment and 48 hours after calving, and from calves at birth, and at seven, 14 and 56 days old. Five per cent of calves born (six of 122) to cows fed grass silage and none born to cows fed hay were affected by CJLD. The diet and health status of calves were not significantly (P greater than 0.05) associated with the plasma concentration of 1,25(OH)2D. The plasma calcium concentration declined with age of the calves (P less than 0.05) but was not affected by the occurrence of CJLD. Plasma phosphorus and magnesium concentrations in calves born to cows fed silage were higher (P less than 0.05) than in those born to cows fed hay. At birth and seven days old, plasma phosphorus concentrations were higher (P less than 0.05) in CJLD-affected calves than in healthy calves but the plasma concentration of IGF-1 was not different (P greater than 0.05). It was concluded that the high plasma phosphorus concentrations in CJLD-affected calves and their dams could be related to the aetiology of the CJLD condition in calves. PMID- 1410816 TI - Effect of cyclophosphamide immunosuppression on the immunity of turkeys to viral rhinotracheitis. AB - Turkey poults, free of antibodies to turkey rhinotracheitis (TRT) virus were treated with cyclophosphamide on days 1, 2 and 3 after hatching and vaccinated by eyedrop when 10 days old with a Vero cell-attenuated preparation of TRT virus. No ELISA antibodies to TRT virus developed in the sera of these poults but they were as resistant to virulent virus challenge 21 days later as vaccinated groups which were not cyclophosphamide-treated but produced humoral antibodies. Following challenge with virulent virus at 31 days old cyclophosphamide-treated unvaccinated poults developed a more severe clinical response than untreated birds and had higher virus titres in tracheal swabs. The findings show that the respiratory tract of turkeys may be resistant to TRT despite the absence of ELISA antibodies in the serum. PMID- 1410817 TI - Protective effects of an oral microencapsulated Mycoplasma hyopneumoniae vaccine against experimental infection in pigs. AB - Oral microencapsulated Mycoplasma hyopneumoniae vaccines were tested for their ability to prevent mycoplasmal pneumonia in pigs. Eighteen four-week-old specific pathogen free pigs were divided into six groups of three. Each pig of groups 1 to 4 was inoculated intramuscularly with formalin-inactivated M hyopneumoniae in adjuvant and boosted orally 14 days later with four different microencapsulated vaccine microspheres. Group 5 was used as a positive control. All 15 pigs of groups 1 to 5 were challenged at 28 days after the first vaccination by an intratracheal inoculation of pneumonic lung suspension. The three pigs of group 6 were used as a negative control. All four vaccinated groups showed some protection when challenged, but the protection was more solid in pigs boosted with vaccine D (group 4) which contained less porcine serum in the microsphere. The study indicates that oral vaccination with M hyopneumoniae could play a role in prevention and eradication of mycoplasmal pneumonia in the pig. PMID- 1410818 TI - Tissue distribution of monomeric glutathione peroxidase in broiler chicks. AB - It is known that there are two kinds of enzymes which show glutathione peroxidase activity, 'classical' glutathione peroxidase and glutathione S-transferase. Recently, a third enzyme was found, monomeric glutathione peroxidase, in broiler chick liver cytosolic fraction. To gain an insight into the possible physiological role of the monomeric glutathione peroxidase, the distribution of this enzyme in other broiler tissues was studied. The monomeric glutathione peroxidase was found in all tissues examined and in erythrocytes. The percentage of the total glutathione peroxidase activity accounted for by the monomeric enzyme ranged from 4 per cent in erythrocytes to 28 per cent in liver. Livers from three avian and two mammalian species contained the monomeric glutathione peroxidase. The contribution of the monomeric enzyme to total glutathione peroxidase activity with cumene hydroperoxide was high in poultry livers, while only trace monomeric glutathione peroxidase activity was found in mammalian livers. Chick monomeric glutathione peroxidase showed high activity toward phospholipid hydroperoxide. Thus, monomeric glutathione peroxidase might be an important enzyme in reducing membrane lipid hydroperoxides in birds. PMID- 1410819 TI - Effects of age, sex and housing on the trabecular bone of laying strain domestic fowl. AB - To determine the effects of age, sex and housing on trabecular bone volume, samples were collected from groups of male and female domestic fowl housed in cages or floor pens from four to 60 weeks old. Between 25 and 60 weeks old, trabecular bone volume decreased by 25 per cent in sections of free thoracic vertebrae (T5) from female birds, the loss occurring at an earlier age in caged birds. Over the sample period, TBV in male caged birds diminished by 35 percent, but male floor birds showed no reduction in trabecular bone volume. At 60 weeks, trabecular bone volume was 30 per cent greater in male caged birds and 40 per cent greater in male floor birds than in the corresponding females. In reproductively active females, no trabecular osteoid was observed, indicating no new trabecular bone formation. However, trabecular osteoid was present in two birds aged 60 weeks which had regressed ovaries. Osteomalacia was not seen in any of the bone samples. PMID- 1410820 TI - Variations in blood flow to and from the bovine mammary gland measured using transit time ultrasound and dye dilution. AB - Blood flow across the lactating bovine mammary gland was measured by two techniques. The use of transit time flow probes appeared to give flows which correlated well with dye dilution in only one of five cows, although the relative changes in flow were similar between the techniques in four of the cows. Further studies were made on the effect of posture on mammary blood flow using both techniques. The crossover of venous blood from one side of the mammary gland was also studied using the dye dilution technique, and revealed large differences between animals and also with posture. These observations suggest that particular care should be taken when sampling blood from the milk vein of cows, if a representative sample is required. Changes in blood flow with posture may be indicative of a repartitioning of flow within the body, and the physiology of such a mechanism would be of interest in itself. The control of this mechanism may be useful in modifying blood flow to the mammary gland and thus milk yield, since blood flow is related to the level of milk production. PMID- 1410821 TI - Pyrolysis mass spectrometry of Listeria monocytogenes isolates from sheep. AB - Forty-eight isolates of Listeria monocytogenes from sheep and silage, involved in five small outbreaks of listeriosis, were compared by pyrolysis mass spectrometry (PyMS). The method clustered isolates from single animals, and showed that epidemiologically associated isolates were closely related to each other. PyMS is a simple technique capable of analysing large numbers of samples daily, and its application in veterinary studies should help to elucidate the epidemiology of listeriosis. PMID- 1410822 TI - Comparison of endocrine changes and ultrasound as means of identifying ovulation in the bitch. AB - Twenty bitches were monitored through pro-oestrus and oestrus using both circulating plasma hormone levels and ultrasonic examination of the ovaries. Using luteinising hormone (LH) as being the generally accepted optimum indicator of the day of ovulation, comparisons were made of the accuracy of progesterone and ultrasound to identify ovulation. Progesterone agreed with LH in 12 of 20 bitches and was within one day in seven of the other eight. Ultrasound was less accurate in that only four of the 16 estimates agreed, with a further six being within one day. However, if only the bitches which were examined by ultrasound with the latest equipment were included, while only three of 11 coincided, six of the remaining eight were within one day of the LH estimated ovulation. It is concluded that, at present, of the rapid assessments, the measurement of plasma progesterone is a better estimator of ovulation than ultrasound. PMID- 1410823 TI - Pathophysiology of ovine trypanosomiasis: ferrokinetics and erythrocyte survival studies. AB - The haematological changes, erythrokinetics and ferrokinetics of sheep were investigated after infection with Trypanosoma congolense. Following the detection of parasites in blood, the infected sheep developed macrocytic hypochromic anaemia. Studies with 51Cr-red cells, 125I-albumin and 59Fe as ferric citrate 11 weeks after infection revealed that infected sheep had significantly lower mean circulating red cell volumes but higher plasma and blood volumes than control sheep. The infected sheep also had enhanced erythropoietic activity as judged by significantly higher plasma iron turnover rates, faster disappearance of radio labelled iron and higher iron incorporation rates than control sheep. The rate of disappearance of 51Cr-labelled red cells was greater in infected than in control sheep. It was concluded that the anaemia observed at this stage of infection was due to an increased rate of removal of red cells from the circulation coupled with haemodilution, with no evidence of dyshaemopoiesis. PMID- 1410824 TI - Immune-mediated disease in the old English sheepdog. AB - Immunological data are reported from 19 cases of immune-mediated disease recorded in the old English sheepdog breed in Western Australia between 1978 and 1989. The conditions included autoimmune haemolytic anaemia (seven), idiopathic thrombocytopenia (one), Evans' syndrome (five), multiple myeloma (two), systemic lupus erythematosus (one), discoid lupus erythematosus (one) and hypothyroidism (two). The most consistent serological findings were raised serum IgG (60 per cent), depressed serum IgM (60 per cent) and the presence of multiple autoantibodies (anti-red blood cell 78 per cent, antinuclear antibody 44 per cent, rheumatoid factor 19 per cent). An underlying, breed-related disorder of immune regulation may account for these observations. PMID- 1410825 TI - In vitro studies and in vivo immunisation with the first viral haemorrhagic septicaemia viruses isolated in Spain compared to international reference serotypes. AB - The first five viral haemorrhagic septicaemia virus (VHSV) isolates found in Spain were examined for in vitro growth characteristics, neutralisation by trout antiserum and immunisation challenge of trout fingerlings by water immersion. The viruses had come from different host species in various geographical locations in different years. Three reference VHSV serotypes (F1, F2 and 23.75) were also included in the study. There appeared to be little relationship between the in vivo delay of mortality or the protection of the immunised trout after challenge and the in vitro characteristics studied. In contrast to the in vitro results, the in vivo delay of mortality suggested a closer relationship of the Spanish VHSV isolates to the F2 serotype than to the F1 or the 23.75 serotypes. If the final protection figures are analysed, however, there could be three or four groups of viruses. PMID- 1410826 TI - Response of Trypanosoma congolense in goats to single and double treatment with diminazene aceturate. AB - Diminazene aceturate is one of a limited number of compounds currently marketed for treatment of trypanosomiasis in cattle, sheep and goats. The pharmacokinetics of the compound in goats suggest that double treatment with diminazene aceturate might enhance the compound's therapeutic activity. A study was therefore conducted in goats using two clones of Trypanosoma congolense, IL 3274 and IL 1180, which were previously shown to be resistant and sensitive, respectively, to single treatment with diminazene aceturate. The results indicated that, as compared to single treatment, double treatment with diminazene aceturate at a dose of 7.2 mg kg-1 bodyweight, at either eight or 24 hour intervals, did not greatly enhance the therapeutic activity of the drug. Furthermore, treatment with the same drug dose eliminated infections with T congolense IL 3274 when treatment was administered 24 hours after infected Glossina morsitans centralis had fed, but failed to do so if treatment was delayed until after goats were detected to be parasitaemic. This suggests that failure of T congolense IL 3274 to respond to treatment with diminazene may not be due to drug resistance per se. PMID- 1410827 TI - Genetic evidence for variant selection in the course of dilute passaging of mumps vaccine virus. AB - Mumps vaccine viruses, Leningrad-3 (L-3) strain, harvested at the 8th (8P) and 38th (38P) passage levels, were compared by nucleotide sequencing of the fusion (F) and the phosphoprotein (P) genes, and for replication efficiency in cell culture. Sequencing revealed only one clear base substitution throughout the entire F gene, and no substitutions in the variable 183-nucleotide-long region of the P gene. However, the 8P virus, unlike the 38P variant, contained multiple "ambiguous" nucleotide regions, i.e., additional bases positioned at the level of the principal ones. The 38P variant replicated faster and appeared more homogeneous by its plaque character compared to the 8P virus. The results indicate that the 8P progenitor virus consisted of more than one viral variant and that one of these was selected on repeated passage due to its higher replication efficiency. PMID- 1410828 TI - Localization of cauliflower mosaic virus in the cell nucleus of Brassica pekinensis L. AB - Cauliflower mosaic virus (CaMV) particles were observed in the nuclei of xylem parenchyma cells in Brassica pekinensis L. doubly infected by CaMV and turnip mosaic virus (TuMV). CaMV particles were aggregated in the nucleoplasm but not embedded in viroplasms. This phenomenon was not detected in cell nuclei of mesophyll tissue. Typical features associated with infection by either CaMV or TuMV normally occurred in the cytoplasm of cells of both tissues: two types of viroplasms with embedded CaMV particles and cylindrical inclusions induced by TuMV. Among the main hypotheses which could explain this particular CaMV localization, we checked that it was not the result of the coinfection with TuMV, since we also found CaMV particles in the same place in single infected plants. Other explanations are discussed, including a possible particularity of the infection in xylem tissue or a specific property of an unusual CaMV isolate. PMID- 1410829 TI - Choroidal angiography today and tomorrow. PMID- 1410830 TI - Minimized surgery for retinal detachments with segmental buckling and nondrainage. An 11-year follow-up. AB - A prospective study was conducted of 107 retinal detachments operated on between August 1979 and January 1980, with a complete follow-up period ranging from 11 years to 11.5 years. Proliferative vitreoretinopathy (PVR) stage C1 or C2 was seen in 16 detachments. Surgery consisted of cryopexy and segmental buckling (limited to the area of breaks) with nondrainage. Of the surgical procedures, 71% were radial buckles, 19% circumferential, and 10% radial combined with circumferential buckles. The primary reattachment rate was 92.6%, and 97% after reoperation. During the long-term follow-up period, redetachment occurred in 12.1% of the eyes: 5.6% were classified as early redetachments (between 2 and 4 months), and 6.5% as late redetachments (between 3 and 7 years). Early redetachment was caused by PVR, and late redetachment by new holes. After reoperation, reattachment occurred in 92.6% of the eyes. The predominant cause of final failure was PVR (3.7%). Only one eye had two reoperations. There was a highly significant (P less than 0.001) improvement between preoperative visual function (mean 0.32) and postoperative visual function (mean 0.56) in all 99 reattached eyes during the follow-up period (Mann-Whitney U test). PMID- 1410831 TI - Clinicopathologic study of idiopathic macular pucker in children and young adults. AB - Clinically significant idiopathic macular pucker was observed in 11 patients aged 30 years or younger. In these patients, the tissue was well defined and fibrous in appearance, in contrast to the thin, cellophane appearance that is typical of macular pucker in elderly patients. Vitrectomy and epiretinal membrane peeling were performed in each case. Visual acuity improved after surgery in seven cases and worsened in one case, and follow-up data was not obtained in three cases. Recurrent membranes were noted in four cases, two of which detached spontaneously. Ultrastructural studies were performed on the removed specimens in each case. Myofibroblasts, myoblastic differentiation of retinal pigment epithelial cells and fibrous astrocytes, and new collagen formation were more common than in idiopathic macular pucker in older patients. The clinical and ultrastructural features of juvenile macular pucker reflect more rapidly changing, contractile tissue compared with the usually more quiescent features in series involving older patients. PMID- 1410832 TI - Surgical treatment of retinal detachment in the choroidal colobomas. AB - Seven eyes from seven patients with retinal detachment and choroidal coloboma (with or without optic disc involvement) were treated. The retinal break was always inside the colobomatous area, except in the cases with evidence of peripheral retinal breaks. In order to produce reattachment of the retina, vitrectomy procedures with removal of posterior hyaloid were used. Drainage of subretinal fluid was performed through the break in the area of the coloboma, with simultaneous fluid-air exchange. Previously undetected retinal breaks were identified by inspecting for the presence of schlieren in the colobomatous area during fluid-air exchange. A peripheral scleral buckle was then applied. Argon laser endophotocoagulation was performed, but when the coloboma involved the optic disc, red krypton endophotocoagulation was used. Retinal reattachment was achieved in all cases. PMID- 1410833 TI - Xanthic scotoma and yellow foveolar shadow caused by a pseudo-operculum after vitreofoveal separation. AB - The biomicroscopic detection of a small opacity (pseudo-operculum) suspended in front of the normal foveal retina is a sign of vitreofoveal separation. This report concerns five patients in whom slit-lamp illumination of the pseudo operculum produced a yellow spot (shadow) on the adjacent pigment epithelium. This occurred in two patients who presented because of a small yellow central scotoma. In one patient, the yellow spot and scotoma disappeared after complete posterior vitreous separation. One patient presented because the referring physician misinterpreted the yellow spot as a Stage 1 impending macular hole. PMID- 1410834 TI - Traction retinal detachment due to preretinal proliferation of surface epithelium. AB - A seven-year-old boy sustained severe blunt trauma with globe rupture. After repair of the globe and lensectomy and vitrectomy, a fistula was noted along with epithelial downgrowth on the posterior surface of the cornea. Extensive peripheral preretinal membrane formation resulted in traction retinal detachment. The fistula was excised and the preretinal membranes were removed. Pathologic examination of the membrane revealed it to be composed of surface epithelium. Retinal reattachment was achieved with intravitreal injection of silicone oil. This case illustrates that surface epithelium can proliferate on the inner retina and can lead to tractional retinal detachment. PMID- 1410835 TI - Primary nonfamilial amyloidosis of the vitreous. A light microscopic and ultrastructural study. AB - Nonfamilial amyloidosis, a form of primary amyloidosis accompanied by vitreous opacity, is a rare condition. Here, a 50-year-old man developed strand-like opacities in the vitreous of both eyes. Pars plana vitrectomy was performed to improve the patient's vision. The vitreous specimens showed typical light microscopic and ultrastructural features of amyloidosis. PMID- 1410836 TI - Foveal hypoplasia in complete oculocutaneous albinism. A histopathologic study. AB - Histopathologic and ultrastructural findings in an eye from a patient with complete oculocutaneous albinism are reported. Examination revealed posterior embryotoxon, high myopia, no foveal differentiation, and absence of melanin pigment in all ocular structures. A few nonmembrane-bound electron-dense granules of lipofuscin were present in the iris and retinal pigment epithelial cells. PMID- 1410837 TI - Comparison of retinal photocoagulation using pulsed frequency-doubled neodymium YAG and argon green laser. AB - The photocoagulation effects on retinal and choroidal tissue of the argon green and pulsed frequency-doubled neodymium-YAG lasers were examined in rabbit eyes. In contrast to the continuous wave output of the argon green laser, the pulsed frequency-doubled neodymium-YAG laser produces a series of 1 microsecond pulses emitted at a repetition rate of 10 kHz. The high repetition rate results in pulse averaging, allowing relatively low peak powers to be used while producing average powers capable of thermal tissue effects. Photocoagulation lesions in the rabbit retina were placed in pairs using each of the lasers. Light microscopic comparison of the argon and neodymium-YAG burns revealed morphologically similar lesions for up to 14 days after photocoagulation, with damage predominantly at the level of the retinal pigment epithelium and outer retina. The high repetition rate, pulsed frequency-doubled neodymium-YAG laser produced thermal tissue effects similar to the continuous wave argon green laser. PMID- 1410838 TI - Comparison of three permanent intraocular magnets. AB - A comparison was performed of three small-gauge, permanent, rare-earth, intraocular magnets to assist the posterior segment surgeon with the decision as to which magnet to purchase or to use in different clinical situations. The magnetic force was measured at varying distances from the instrument tip using a 1/8-inch steel ball as the test object. There were small differences in magnetic strength between the three instruments that may have clinical significance in certain situations. Two of the instruments had a retractable magnet within an outer sleeve, allowing for controlled attraction and release of a magnetic foreign body by the surgeon. PMID- 1410839 TI - Retinal cartography. An analysis of two-dimensional and three-dimensional mapping of the retina. AB - The current two-dimensional (2D) retinal drawing chart is an azimuth equidistant representation of the retina. The distortion produced by this chart was analyzed and compared to other 2D projections, such as stereographic, equal area, and orthographic maps of the retina. Circumferential distortion was calculated for lesions at varying distances from the macula using the azimuth equidistant retinal map and was found to increase exponentially as a function of the distance from the macula. Circumferential distortion was 57.1% at the equator, 88.5% 3 mm anterior to the equator, and 137.8% 6 mm anterior to the equator. A three dimensional (3D) model of the retinal surface was created using 3D computer assisted design (CAD) software. This 3D model was able to represent retinal lesions such that their true size, shape, location, and orientation were all conserved. Retinal lesions could be viewed from multiple angles and examined in cross section. The use of 3D CAD software coupled with ultrasound or magnetic resonance imaging data has the potential to represent retinal lesions more accurately than current methods. PMID- 1410840 TI - Regional variation and control of cutaneous gas exchange in bullfrogs. AB - Previous work has demonstrated regional differences in morphometric diffusing capacity and cutaneous blood flow in anuran amphibians, leading to the prediction of a higher rate of cutaneous gas exchange across the dorsal skin of bullfrogs. Regionally measured cutaneous O2 and CO2 flux rates (MO2 and MCO2) support this prediction: flux rates across the dorsal skin are 15-32% greater than across the ventral skin in both pulmonary ventilating and apneic (anesthetized) bullfrogs. The rates of cutaneous gas exchange were much greater in anesthetized frogs; however, MO2 and MCO2 did not increase in parallel, which decreased the cutaneous respiratory exchange ratio from 3.5 to 2.0 in apneic frogs. Regional differentiation in cutaneous gas exchange suggests the possibility of independent regulation; however, cutaneous MCO2 varied little in response to changes in O2 content above these regions, neither in the anesthetized nor awake bullfrogs. The bullfrogs are able to increase whole body cutaneous gas flux during prolonged apnea but were not able to respond to changes in local O2 content. PMID- 1410841 TI - Effects of analysis method and forcing waveform on measurement of respiratory mechanics. AB - The respiratory system has been shown to exhibit nonlinear mechanical properties in the frequency (f) range of normal breathing, manifested by tidal volume (Vt) dependence. Calculations of respiratory system resistance (R) and elastance (E) from pressure-flow measurements during external forcing at a given f may be ambiguous, especially if non-sinusoidal forcing waveforms are used. We evaluated the degree to which R and E depended upon: (1) analysis method (Fourier transform, multiple regression and pressure-volume loop analysis) and; (2) shape of the forcing waveform (sinusoidal, quasi-sinusoidal and step). We measured pressure and flow at the mouth of 5 healthy, awake subjects, relaxed at functional residual capacity, during forcing with the three different waveforms in the normal range of f (0.2-0.6 Hz) and Vt (250-750 ml). During sinusoidal forcing, E and R were not affected by analysis method (P greater than 0.2). With Fourier transform and multiple regression, E was not affected by waveform shape (P greater than 0.05); with loop analysis, E was slightly (less than 10%) higher during quasi-sinusoidal and step forcing than during the sine (P less than 0.05). R was least affected by waveform shape with Fourier transform. We conclude that, in the f and Vt range of normal breathing: (1) respiratory system impedance is 'quasi-linear,' i.e. despite dependencies of R and E on Vt, non-linearities are not large enough to restrict interpretation of R and E at a given f and Vt; (2) it may be possible to measure R and E using non-sinusoidal forcing waveforms available on most clinical ventilators, incurring only modest error. PMID- 1410842 TI - Inspiratory muscle activity during pulmonary edema in anesthetized dogs. AB - Pulmonary edema is known to induce a rapid and shallow breathing pattern. However, its effects on the level and pattern of distribution of motor activity to the respiratory muscles is unclear. In the present study we evaluated the effect of oleic acid induced pulmonary edema on the electrical activity of the inspiratory muscles (costal and crural diaphragm and parasternal and external intercostal muscles) in the dog, and related it to the transdiaphragmatic pressure and ventilatory parameters over the course of CO2 rebreathing. Pulmonary edema, reflected by a 7.1 +/- 0.6 wet to dry ratio, decreased lung compliance by 57%, increased pulmonary shunt to 35%, and was associated with a rapid and shallow breathing pattern. When compared at equal levels of PCO2 during CO2 rebreathing before and during edema, ventilation and mean inspiratory flow were increased only at lower levels of hypercapnia and their responses to increasing levels of PCO2 were significantly diminished during edema. Transdiaphragmatic pressures were elevated during edema as compared to control values. The rate of rise of the electrical activity of all inspiratory muscles increased significantly during edema at all levels of PCO2. Peak activity, however, remained unchanged, due to shortening of the inspiratory duration. The EMG responses to progressive hypercapnia were not affected by edema. Pulmonary edema did not change the pattern of breathing and neural output to the inspiratory muscles in vagotomized dogs. We conclude that stimulation of pulmonary proprioreceptors during edema increases neural output to all inspiratory muscles. The neural response to hypercapnia is not altered by edema, and is additive to the vagal input. The ventilatory response to CO2 is blunted during severe edema, due to alterations in lung mechanics. PMID- 1410843 TI - Menthol in the upper airway depresses ventilation in newborn dogs. AB - Upper airway cooling depresses ventilation in the newborn dog. Since airway cooling stimulates laryngeal cold receptors and inhibits laryngeal mechanoreceptors, the type of afferent ending responsible for this reflex cannot be easily identified. l-menthol, a specific stimulant of cold receptors in the absence of any cooling, has been used to ascertain the discrete role of upper airway cold receptors in this ventilatory depression. Experiments were carried out in 8 anesthetized 7-14-day-old dogs breathing through a tracheostomy with the upper airway functionally isolated. Constant flows of warm air (37 degrees C), with and without addition of l-menthol, and cold air (25 degrees C) were delivered through the upper airway in the expiratory direction. As compared to warm air trials, cold air and warm air + l-menthol trials greatly reduced ventilation (57.5 +/- 10.7% and 52.8 +/- 11.7% of control, respectively; P less than 0.01) mostly due to a prolongation of Te (291.2 +/- 106.4% and 339.2 +/- 90.0%, respectively, P less than 0.01). Section of the superior laryngeal nerve abolished the response to cold air. However, a residual depressive effect of l menthol was still present in 3 of 5 animals and was abolished by nasal anesthesia, suggesting the involvement of nasal cold receptors. The results suggest that in the newborn dog stimulation of laryngeal cold receptors, without any concurrent inhibition of laryngeal mechanoreceptors, is a sufficient stimulus to cause respiratory depression. PMID- 1410844 TI - Hypoxia-induced ANP secretion in subjects susceptible to high-altitude pulmonary edema. AB - We investigated the effects of acute hypoxia (10% O2) on plasma level of atrial natriuretic peptide (ANP) and pulmonary hemodynamics in five subjects with a history of high-altitude pulmonary edema (HAPE). Plasma renin activity and plasma levels of aldosterone, epinephrine and norepinephrine were also measured. The plasma ANP levels in HAPE-susceptible subjects rose significantly in response to 10% O2 (from 34.8 +/- 5.4 to 51.4 +/- 7.3 pg.ml-1; P less than 0.05), not associated with any increase in either atrial pressure. Compared with six control subjects, the rise of ANP level was greater in HAPE-susceptible subjects (16.6 +/ 4.4 vs 3.9 +/- 1.2 pg.ml-1; P less than 0.05). There was a significant positive correlation between the rise of ANP level and the increase of pulmonary arterial pressure. No significant difference was observed in any of other hormonal responses to acute hypoxia between the two groups. We interpret these results as indicating that the ANP secretory response to acute hypoxia in HAPE-susceptible subjects, which is not mediated by an increase in atrial pressure, may be greater than that in nonsusceptible subjects in association with a greater pressor response of pulmonary circulation. PMID- 1410845 TI - Effect of increased metabolic rate on oxygen isotopic fractionation. AB - 16O16O is preferentially used over 18O16O (a stable isotope of oxygen comprising about 0.2% of atmospheric O2) as oxygen is consumed during respiration in humans (Epstein and Zeiri, 1988, Proc. Natl. Acad. Sci. USA 85: 1727-1731). To test the hypothesis that oxygen isotopic fractionation is related to the metabolic rate, 8 healthy adults performed 5 min of constant work rate cycle ergometer exercise below and above their anaerobic threshold. Moreover, 3 subjects performed an incremental exercise to the limit of tolerance. Oxygen uptake (VO2) was measured breath by breath. Samples of the exhaled breath for oxygen isotope measurement were obtained at rest and at various times during exercise and recovery. Oxygen isotopic fractionation was determined by isotope ratio mass spectrometry and calculated as the ratio of the degree of fractionation to the oxygen consumed in the breath sample (Z value). For the constant work rate protocol, both low and high intensity exercise resulted in a significant decrease in Z compared to the rest values (P less than 0.01). However, for the high intensity exercise the reduction in fractionation was greater compared to the low intensity protocol (P less than 0.05). For the incremental test, there was a significant negative correlation between oxygen isotopic fractionation and VO2 expressed as percent of the maximal oxygen uptake (r = -0.91, P less than 0.0001). These data suggest that during exercise low-fractionating processes become more important as limiting steps for O2 transport. PMID- 1410846 TI - Uneven perfusion within single cat muscles: nitric oxide and citrate synthase play no role. AB - There is an unexplained, marked regional heterogeneity in perfusion within single skeletal muscles both in dogs and rabbits. We asked if a similar distribution of perfusion was present within cat muscles. If present, we wanted to assess the possible roles of nitric oxide (NO) mediated vasodilation and citrate synthase (CS) activity for the regulation of this perfusion pattern. Perfusion was determined in 0.25 g regions within the gastrocnemius muscles by trapping of microspheres. We studied awake or anesthetized cats before and during inhibition of NO-formation using N-monomethyl-L-arginine. The CS activity was determined in homogenates of these regions. The coefficient of variation corrected for the Poisson distribution of microspheres (CVc) for the regional perfusion averaged 0.39. Despite a 25% reduction in perfusion to the whole muscles as compared to control, the uneven distribution of perfusion was not affected by blocking NO formation. Regional perfusion was not correlated to regional CS activity. Even if the regional distribution of CS activity also showed a scatter, mean coefficient of variation corrected for methodological error = 0.20, it was markedly less than that for perfusion. We conclude that neither NO vasodilation nor CS activity play an important role in the regulation of the regional perfusion pattern within single cat muscles. PMID- 1410847 TI - Liquid volume, Na+ and mannitol concentration in a hypertonic mannitol-Ringer hydrothorax. AB - In anesthetised rabbits with a 2 ml hypertonic mannitol-Ringer hydrothorax in the right space 30 mM/L mannitol were required for an unchanged volume of the hydrothorax after 60 min. [Na+] in the pleural liquid 10, 30 and 60 min after this hydrothorax was 8, 7 and 5 mEq/L, respectively, lower (P less than 0.01) than the initial one and that in a Ringer-hydrothorax. This seems due to the active transport of Na+ out of the pleural space followed by little water because of the osmotic pressure exerted by mannitol. This finding provides further evidence for an active transport without using inhibitors, and implies that the mesothelium offers an appreciable resistance to small solute diffusion. Mannitol concentration, measured at corresponding times from the activity of labeled mannitol, was 76, 68 and 56%, respectively, of the initial one (24.5 mM/L). From 30 to 60 min 6.5 microM of mannitol left the right space mainly by diffusion. The diffusional permeability of the mesothelium was indirectly assessed from the diffusional outflux of mannitol, the surface of the pleural space, and an estimate of mannitol concentration in the interstitium next to the mesothelium: it is smaller than that found in vitro. PMID- 1410848 TI - Lung growth in newborn guinea pigs: effects of endurance exercise. AB - Newborn Hartley albino guinea pigs were exercised daily on a rodent treadmill at 25 m/min, 0 degree grade for a maximum of 1 1/2 h. Groups were exercised for 1, 2 and 3 weeks. Controls were age-matched sedentary animals. A separate group of animals was sacrificed after 12 h of life to establish baseline lung growth data. A morphological and biochemical comparison was made between the lungs of exercised and sedentary animals. No effect of exercise on lung growth was observed. After 2 weeks of exercise animals had diminished somatic growth compared to the controls. The data was pooled from exercised and control guinea pigs at 1 and 3 weeks, at which time there were no differences, in order to obtain normal growth data. The only change between 0 week and 1 week was a slight increase in femur length. Between 1 week (and also 0 week) and 3 weeks there were significant increases in lung volume, lung weight, protein content, inter alveolar wall distance, mean chord length of alveoli and ducts, and gas exchanging surface area. The guinea pig lung is well alveolated at birth and there was no evidence of subsequent alveolar multiplication. Enlargement of airspaces suggested that lung growth was primarily brought about by dilation. The lack of alveolar multiplication following exercise may be due to the fact the alveoli are fully developed at birth. PMID- 1410849 TI - Pathophysiology and management of anemia in chronic progressive renal failure. AB - Hypoproliferative anemia is a predictable and serious complication of progressive renal failure and contributes significantly to the overall morbidity of the uremic state. Until recently, there has been no satisfactory therapy to resolve the anemia. Now the anemia can be explicitly corrected with erythropoietin replacement therapy, and the clinical debility generally attributable to renal insufficiency can be lessened and retarded. Anemia must no longer be regarded as an intractable consequence of the uremic syndrome and should be managed as conscientiously as the other polysystemic features of uremia. PMID- 1410850 TI - Status of renal transplantation in the 1990s. PMID- 1410851 TI - Glomerulonephritis. PMID- 1410852 TI - Chronic renal disease and potassium depletion in cats. PMID- 1410853 TI - Nephrocalcinosis caused by hyperparathyroidism in progression of renal failure: treatment with calcitriol. AB - Nephrocalcinosis is accepted to contribute to the progression of renal failure. We have reviewed evidence that nephrocalcinosis is caused directly by the excess parathyroid hormone produced in renal disease. Evidence that hyperparathyroidism in uremic patients results from calcitriol deficiency and the mechanisms by which this comes about have been discussed. We have shown that renal secondary hyperparathyroidism can be eliminated or substantially reduced without increasing blood calcium using a low-dosage regimen of calcitriol. Decreasing PTH concentrations to or near normal alleviates this hormone's toxicity to many organs, including the kidneys. Potential benefits for the uremic patient include an increase in the quality and length of life. Calcitriol treatment provides a powerful means to reduce PTH concentration in uremic patients that may not be achieved with other methods. Further prospective clinical studies of uremic dogs and cats are warranted to document preservation of renal function and histology during calcitriol treatments. PMID- 1410854 TI - Hypertension and chronic renal failure. PMID- 1410855 TI - High dietary protein intake does not cause progressive renal failure in dogs after 75% nephrectomy or aging. PMID- 1410856 TI - Dietary protein restriction: some unanswered questions. PMID- 1410857 TI - The influence of dietary protein intake on progression of chronic renal failure in dogs. PMID- 1410858 TI - The role of HLA matching for cadaveric renal transplants in the cyclosporine era. PMID- 1410859 TI - Antilymphocyte antibodies in the treatment of allograft rejection: targets, mechanisms of action, monitoring, and efficacy. PMID- 1410860 TI - The goal of specific immunologic unresponsiveness in clinical kidney transplantation. PMID- 1410861 TI - Clinical immunosuppressive regimens and clinical results in renal transplantation. PMID- 1410862 TI - Patient and renal allograft survival in the late posttransplant period. AB - Finding the proper balance between too much and not enough immunosuppression is just as important in the late posttransplant period as it is during the first year after transplantation. In general, too much immunosuppression leads to an increase in patient mortality, whereas inadequate immunosuppression can lead to an inordinately high rate of allograft failure (Fig 5). In the late posttransplant period, patient and allograft survival are both critically dependent on the degree of immunosuppression and on the long-term side effects of the agents used to achieve this immunosuppression. Adequate immunosuppression is important in treating and preventing the acute allograft rejection episodes that are common during the first year after transplantation (Fig 6). Some data suggest that the severity of early acute rejection episodes may influence the development of chronic rejection, the most common cause of graft failure in the late posttransplant period. Otherwise, the role of immunosuppression in treating and preventing chronic rejection is unclear. The discontinuation of immunosuppression by noncompliant patients is a major cause of late graft failure. Whether the nephrotoxicity of CsA will also result in graft failure in the very late posttransplant period is still unknown. The agents used to achieve immunosuppression, along with decreased graft function and proteinuria, contribute to hypercholesterolemia, hypertension, and hyperglycemia. These and other risk factors have a negative impact on both graft and patient survival. Thus, immunosuppression is directly, or indirectly linked to most of the common causes of death and graft failure after renal transplantation. Although potent new immunosuppression protocols have increased the rate of short-term patient and allograft survival after renal transplantation, future advances in long-term survival after renal transplantation will depend on improvements that are effective in the late posttransplant period. Currently, the best approach to preventing complications in the late posttransplant period is to maintain a vigilant, comprehensive program of on-going medical care. The minimal amount of immunosuppression required to prevent allograft rejection should be used, while adhering to the principle that it is better to lose the graft than to lose the patient. PMID- 1410863 TI - Clinical approach to viral and fungal infections in the renal transplant patient. PMID- 1410864 TI - Circulating immune complexes in renal injury. PMID- 1410865 TI - T cells and macrophages and their role in renal injury. PMID- 1410866 TI - The role of the complement system in renal injury. PMID- 1410868 TI - Eicosanoids in immune-mediated renal injury. PMID- 1410867 TI - Cytokines and growth factors in renal injury. PMID- 1410870 TI - [Non parenchymatous cells of the liver and viral infection]. PMID- 1410869 TI - [Prevention of infectious endocarditis]. PMID- 1410871 TI - [Bone localizations disclosing Hodgkin's disease. Apropos of 11 cases]. AB - The authors report 11 cases of Hodgkin's disease in which the first sign was due to bone involvement. Such observations are rare and raise diagnosis delays (Means: 5, 6 months in this series). Modern medical imaging techniques (scintigraphy, CT scan, magnetic resonance imaging) are very useful to an earlier diagnosis which will be better confirmed by lymph node biopsy given the poor information yielded by osseous cytology and/or histology. The elective localisation in bones belonging to the axial skeleton seems to support the hypothesis of a contiguous osseous involvement from lymphoid organs in contact with bones. Evolution with chemotherapy and radiotherapy is very similar to that observed in patients without bone involvement. PMID- 1410872 TI - [Cost effectiveness of Doppler-echocardiography in the diagnosis of deep venous thrombosis of the lower limbs. Theoretical calculation from a prospective series of 511 patients]. AB - The management of deep venous thrombosis has non-negligible financial implications due not only to the high frequency of clinical suspicion--and therefore to the methods used a positive diagnosis--but also to the overall cost of management. To evaluate the expenditure incurred for the diagnostic tests, 511 patients suspected of deep venous lower limb thrombosis were examined clinically, then by Duplex ultrasonography combined with plethysmography. Whenever a suspected phlebitis was detected by this method, or at random if it was not, phlebography was performed. The 185 phlebography/ultrasonography comparisons enabled us to extrapolate the results obtained to all 511 patients and thus to compare the theoretical cost of 4 decisional algorithms according to the diagnostic criteria utilized. Our conclusions were as follows: the clinical diagnosis alone is not cost-effective, whereas Duplex ultrasonography is reliable and, compared with phlebography, saves more than 1,500,000 francs per year, including 1,000,000 francs saved on the global hospital budget in France. Phlebography used in each proximal venous thrombosis for accurate localization of the upper end of the clot does not significantly increase the cost: the annual savings on systematic phlebography are still above 1,200,000 francs, including 800,000 francs to the benefit of public hospitals. PMID- 1410873 TI - ["New cytology" and diagnosis of malignant tumors]. AB - Cytology is an old method of diagnosis: it is the microscopical observation of cells in the aim of their identification, of the recognition of morphological abnormalities to obtain diagnosis or prognosis informations. During the last 20 years, new technics have been developed: 1) Immunocytochemistry permits the identification of the tissue or the organ of which a tumoral cell population is born, the determination of its stage of differentiation, its kinetic and the diagnosis of bone marrow or lymph node metastasis. 2) With in situ molecular biology, it becomes possible to detect, at the cell level, virus, oncogenes or chromosomic abnormalities. 3) Flow and image cytometry are easy means for DNA content determination and for an objective and reproducible cell definition. None of these methods are able, at this time, to replace the cytological analysis, but they are useful, sometimes necessary, for the diagnosis and the prognosis evaluation of malignancy. PMID- 1410874 TI - [Diagnosis of muscular intolerance during exercise caused by enzyme deficiency in adults]. AB - The exertional muscle pain syndrome in adults is expressed by recurrent episodes of pain and/or episodes of acute rhabdomyolysis, sometimes with transient myoglobinuria or even acute renal failure. The enzymatic origin of this syndrome is suggested by a familial history, by its usual onset during childhood or adolescence, and by its recurrent attacks usually, but not exclusively, caused by exercise. The aetiological diagnosis, suggested by the clinical context and some dynamic tests, is almost always based on good histological and biochemical examinations of the muscle biopsy. PMID- 1410875 TI - [Lymphedema: is there a treatment?]. AB - More than hundred medical treatments for lymphedema have been described. This very high number shows the evidence of difficulties: lymphatics are very small vessels, under low pression and velocity respondent to spontaneous quiet lymphatic contractions. The treatments can be listed in 3 groups: 1) physiotherapeutic methods, increasing lymphatic flow: cold, field stimulation, manual lymph drainage, intermittent compression, heat; 2) drugs: venous agents (flavone, benzo-pyrone), and intraarterial lymphocytes injection, promoting lymphatic flow or increasing normal proteolysis by macrophages in order to remove trapped proteins from interstitial fluid; 3) surgical procedures subdivided in 2 groups: excisional techniques and bridging drainage techniques; radical or partial excision removes involved subcutaneous tissue, recently by the way of liposuction; Efforts to drain lymphedema by subcutaneous implants, pedical flaps, myocutaneous flaps, omental transposition and intestinal flaps are historical. Microsurgical lymphatic anastomosis to vein (nodo-venous then lymphovenous), and to lymphatic themselves are now performed: lymphatic collectors or venous autografts are interpositioned to by-pass lymphatic blockade with end-to end anastomosis. The free transplantation of a lymphatic flap with its own vascularisation from healthy inguinal nodes to axillary blockade is the last described procedure. Lymphatic anastomosis are not needed. Actually, physiotherapy is always first indicated. Benzo-pyrones are additive drugs. Excisional procedures concern monstruous lymphedema. Microsurgical bridging procedures can be attempted only for secondary lymphedemas. They could be of benefit if physiotherapy and elastic bandages, stockings or sleeves, could then be avoided. Studies assessing independently the efficiency of each procedure are needed. PMID- 1410876 TI - [Involvement of central nervous system disclosing Waldenstrom's disease: demonstration of intrathecal secretion of immunoglobulin M]. AB - We report the case of a 68-year old woman complaining of disorders of memory and persistent headaches in whom the diagnosis of Waldenstrom's macroglobulinaemia (WM) was made. Computerized tomography of the brain showed a butterfly-shaped hyperdensity in the splenium of the corpus callosum, with ventricular dilatation. Magnetic resonance imaging displayed high-intensity signals on T2-weighted sequences. Protein immunoelectrophoresis elicited an IgM kappa peak. The CSF was found to contain proteins and lymphocytes in excess, and immunohistochemical staining confirmed the predominance of anti-kappa and the presence of intrathecal IgM secretion. Chemotherapy was temporarily effective on the memory disorders, but the patient died 26 months after the beginning of treatment. Central nervous system manifestations are seldom observed in WM, and they are now grouped under the name of Bing-Neel syndrome. Psychic disorders are rarely reported. It is suggested that IgM secretion plays a predominant role in the pathogenesis of leucoencephalitis, and this is supported by the finding of intrathecal IgM synthesis. PMID- 1410878 TI - [Constrictive pericarditis in severe seronegative rheumatoid polyarthritis]. AB - Constrictive pericarditis is a rare complication of rheumatoid arthritis, with 78 published cases. We report a new typical case where the pericardial disease was associated with a severe seronegative rheumatoid arthritis of 17 years duration. Constrictive pericarditis generally occurs in men (62.8% of all cases) aged 52.4 +/- 11.5 years. Its clinical features are identical with those of constrictive pericarditis due to other causes. Diagnosis rests on echocardiography and, chiefly, on right heart catheterization. The arthritis is seropositive in 85.7% of the cases, frequently nodular (75%) and advanced. There is no relation between its duration (mean: 9.6 +/- 7.4 years) and the occurrence of the pericardial pathology. The pericardial fluid has no specific abnormality. Histology shows fibrosis and a non-specific inflammatory cell infiltrate. Immunoglobulin and complement deposits in the walls of the pericardial vessels are detected by immunofluorescence. The only treatment is pericardiectomy; without it the disease is constantly lethal. PMID- 1410877 TI - [Rhabdomyolysis caused by simvastatinin a patient following heart transplantation and cyclosporine therapy]. AB - Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are cholesterol lowering agents which may induce rhabdomyolysis. The authors present a case of rhabdomyolysis attributed to simvastatin in a heart-transplant recipient. They stress the probability of a dose-dependent muscular toxicity and the risk of overdosage in patients already under treatment with drugs that interfere with the pharmacokinetics of HMG-CoA reductase inhibitors, notably ciclosporine. PMID- 1410879 TI - [Role of polyols in the development of diabetic complications. Value of aldose reductase inhibitors]. AB - The evidence of sorbitol excess in the crystalline lens of alloxan-diabetic rats has led to anticipate the role of the enzyme aldose-reductase in the pathogenesis of the diabetic cataract. In addition, a number of experimental works have more recently shown the involvement of myoinositol deficiency, which probably results from the sorbitol accumulation. These metabolic pathways are most likely implicated in the pathogenesis of diabetic neuropathy and perhaps additionally in that of microangiopathy. The synthesis of several aldose-reductase inhibitors (AR inhibitors) confirmed experimentally these hypothesis. By reducing the activity of the enzyme aldose-reductase, these substances suppress the adverse metabolic consequences of polyol accumulation, myositol deficiency and dysfunction of the Na+/K+ ATPase dependent sodium activity. Although different experimentations showed that the AR inhibitors could prevent in animals the development of experimental cataract as well as the early functional or later anatomic abnormalities of the diabetic retinopathy and nephropathy, the clinical trials did not clearly support these experimental results in humans. On the other hand, the AR inhibitors were proved to exhibit some efficacy in the early stage of diabetic neuropathy and in incipient nephropathy where they delay the development of albustix positive proteinuria. However, the benefit of an early treatment with AR inhibitors should be confirmed by long term prospective studies, which could also assess the safety of these drugs in chronic administration. PMID- 1410880 TI - [Apropos of the treatment of hypercalcemia]. PMID- 1410881 TI - [Symptomatic hypercalcemia: a therapeutic emergency]. PMID- 1410882 TI - [The glucagonoma syndrome. 3 new cases]. AB - We report three new cases of glucagonoma revealed, 6 to 12 months after its onset, by non-specific and misleading skin lesions associated in all 3 cases with diabetes mellitus, severe deterioration of the general condition and hyperglucagonaemia. Non-invasive methods, such as ultrasonography and computerized tomography (CT), are most helpful to locate the pancreatic tumour. Phlebography with tiered venous blood sampling is useful in difficult cases. A false positive result has been recorded with arteriography. Ultrasonography and CT have yielded two false negative results. The alpha-chain of the chorionic gonadotrophin hormone has limited value in the diagnosis of malignant glucagonoma. Treatment is surgical, but despite it, the prognosis is severe (two of our three patients died), due to the risk of thromboembolism, to cachexia and to metastases that are frequent at the time of diagnosis. PMID- 1410883 TI - [Identification of overtreated hypertension with statistical analysis of 100 consecutive ambulatory blood pressure monitoring]. AB - The data obtained from 100 consecutive ambulatory blood pressure (BP) recordings performed in treated hypertensive patients (60 men, 40 women, mean age 52 +/- 14 years) were analysed to make a choice between several possible definitions of overtreatment and to evaluate the prevalence of patients thus defined as overtreated. Recordings were studied over two periods: diurnal from 9 a.m. to 7 p.m. (100 patients, 37 +/- 5 measurements/patient), and nocturnal from 11 p.m. to 7 a.m. (98 patients, 19 +/- 2 measurements/patient). The patients were first classified on the basis of reference ambulatory BP values according to sex and age. Subnormal levels were found in 25 patients for diurnal SBP, 25 for nocturnal SBP, 13 for diurnal DBP and 33 for nocturnal DBP. Several criteria of overtreatment were then tested, based on the percentile method and on the number of subnormal values: the median DBP was below the 30th reference percentile in 16 patients, and the percentage of subnormal DBP values was above 80% in 18 patients. Clinically, there was little to differentiate these patients from the rest of the population treated. The goal of treatment which, in terms of BP values, is to normalize the ambulatory BP was therefore overshot in 1 out of 5 or 6 patients depending on the criteria adopted. The significance and consequences of overtreatment cannot yet be evaluated. PMID- 1410884 TI - [How to understand mechanisms of metastases]. AB - The dissemination of malignant cells is the result of successive and complex biological steps. In most cases, physiopathological observations can explain the different cases of metastatic spread observed in clinical oncology. Our knowledge of the biological mechanisms involved in tumoral dissemination is poor. However, recent data have disclosed cellular modifications associated with malignant spread: these observations concern physiopathological aspects of the cytoplasmic membrane of malignant cells, their interconnexion with the stroma of tumors, the characterisation of new genes involved in tumoral progression and viral oncogenic mechanisms involved in cervical neoplasia. These data will yield biological parameters of potential value in assessing the metastatic risk of malignant tumors at the time of diagnosis. In the near future, it should be possible to more accurately select patients for antitumoral therapy and to achieve a better understanding of the cellular mechanisms involved in tumoral progression. PMID- 1410885 TI - [Identification of persons with high risk of venous thrombosis]. AB - The aim of identification of patients with high risk of deep venous thrombosis is a selective and more efficiency prophylaxis. Deficiencies of coagulation inhibiting and fibrinolytic proteins are implicated in less than 10% of patients. However there are several clinical situations with an increased risk of thrombosis. Thus the characterization of blood abnormalities as screening tests for the diagnosis of patients at risk is an important goal. PMID- 1410886 TI - [Renovascular hypertension: diagnostic and therapeutic strategy]. AB - Investigations for renal artery stenosis have been greatly facilitated by advances in imaging techniques. Intravenous digital subtraction angiography is now performed in all patients with progressive, drug-resistant hypertension associated with aorto-iliac lesions or with renal impairment induced by angiotensin-converting enzyme inhibitors. Yet the finding of hypertension with renal artery stenosis is not enough to make the diagnosis of renovascular hypertension, this term being reserved to hypertension reversible by revascularization. The selection of patients who may benefit from revascularization rests on urography to explore the excretory and endocrine functions of the ischaemic kidney, as well as on scintigraphy and measurement of renin levels in renal veins before and after administration of captopril. The functional data are completed by vascular exploration which helps in evaluating the usefulness and safety of revascularization: repercussions of hypertension on target organs and extension of the vascular disease to other territories. Revascularization as first-line treatment consists of percutaneous transluminal dilatation; surgery must be reserved to difficult cases, such as arterial obliteration or failed dilatation. PMID- 1410887 TI - [Infertility in a couple. Focus on the different techniques of medically assisted procreation]. AB - In view of the advent of effective medically assisted procreation (MAP) techniques, it is now more necessary than ever to use the most strict and systematized methods in the management of couples who consult for infertility. The authors present the modalities of this management and review the present MAP techniques which are all based on bringing together the gametes in an optimal environment conditioned by the clinical situation of the couple. The main results obtained are presented under the headings: percentage of success, multiple pregnancies prevention policy and future of the children. PMID- 1410889 TI - [Apropos of 2 cases of Scedosporium apiospermum nasosinusal infection]. AB - We report two cases of nasosinusal infection caused by Scedosporium apiospermum and involving the nasal fossa in one case and the maxillary sinus in the other. The course of the disease varied according to the patient's immune status. The otherwise healthy patient (case n. 1) was completely cured by surgery, whereas the immunosuppressed patient (case n. 2) had local extension with pseudotumoral symptoms and lysis of the inter-sinusonasal septum; an early surgical treatment combined with local administration of a specific antifungal agent resulted in an apparent cure, but the patient died a few months later. A review of the literature confirms the invasive potential of this fungus which in immunosuppressed patients (by therapeutic immunosuppressants or by a debilitating disease) becomes a dangerous opportunistic organism. Cultures on Sabouraud's medium provide an accurate diagnosis and enable antifungal drugs to be tested, miconazole being the most regularly effective of them. In healthy subjects surgery is the sole treatment of nasal or sinusal lesions, while in all immunocompromised patients it must be combined with an antifungal treatment. PMID- 1410888 TI - [Pulmonary metastasis of meningioma of the falx cerebri]. AB - We report the case of a woman who had been operated upon for a recurrent meningioma of the falx cerebri which, 22 years after it was discovered, produced pulmonary metastases. Metastases from meningiomas are extremely rare; they affect the lungs in 60% of the cases or, less frequently, the liver or lymph nodes. The factors predictive of secondary dissemination are the site of the tumour, the quality of excision, the histological type (haemangiopericytic meningioma) and the presence of cell necrosis, hypercellularity and strong mitotic activity. PMID- 1410890 TI - [Myopathy in adults caused by acid maltase deficiency. A trial of treatment with high protein diet]. AB - A 21-year old women with rhizomelic muscular deficit and signs of hypercapnia developed acute respiratory failure. Laboratory tests revealed high creatine kinase activity, and electromyograms showed myogenic patterns with a few myotonic discharges. Biopsy of the quadriceps muscle elicited major vacuolar myopathy with glycogen overload. Acid maltase activity was undetectable in muscular tissue. After 7 months on high-protein diet (1540 calories, 37% proteins) there was no clinical or biochemical improvement. The other published cases of acid maltase deficiency treated with high-protein diet are discussed. PMID- 1410891 TI - [Association of IgA linear dermatitis and non-Hodgkin's malignant lymphoma]. AB - The association between linear IgA dermatosis and neoplasia has been the subject of several publications which suggest that the association is not fortuitous. We report a new case in which a non-Hodgkin's lymphoma was associated with a linear IgA dermatosis and underline the need for full evaluation in search of an associated neoplasia. However, the neoplasia-LAD association is not a true paraneoplastic syndrome since the two pathologies seldom follow a parallel course. PMID- 1410892 TI - [Homologies between membrane proteins result in expected or unexpected relations between neuromuscular and erythrocyte diseases]. AB - The advances achieved in biochemistry and molecular genetics have made it possible to demonstrate that the membrane proteins of the erythrocytes belong to protein "families" that are present in most cell membranes and share remarkable structural and functional homologies. Abnormalities of erythrocyte membrane proteins might then totally or partially reflect lesions of other cell membranes that are intrinsically more severe than those of the erythrocytes. Examples of these physiopathogenetic links can be found in congenital diseases where muscular and erythrocytic pathologies coexist. Such are: (1) choreaacanthocytosis supported by molecular abnormalities of the so-called band 3 protein or anion channel; (2) Mac Leod syndrome by deficiency of a membrane protein precursor of Kell antigens; (3) some cases of hereditary spherocytosis associated with qualitative and quantitative ankyrin alterations. Yet, despite the homologies that are known to exist between spectrin and dystrophin, all attempts to use spectrin analysis as marker of Duchenne-Becker muscular dystrophy have met with complete failure, which shows that at this early stage one should refrain from drawing firm physiopathological conclusions from the available data. PMID- 1410894 TI - [Intravascular hemolytic anemia resulting from a dystrophic mitral valve]. PMID- 1410893 TI - [Intravenous immunoglobulins and anti-idiotypic suppression of auto-immunity]. AB - This review summarizes the clinical use of intravenous immunoglobulins (IVIg) in autoimmune diseases and focuses on the mechanisms by which IVIg suppress autoimmune responses. Evidence is presented of a role of IVIg in modulating the regulatory function of the idiotypic network on the expression of the natural and pathological autoimmune repertoires. PMID- 1410895 TI - [Orphan drugs: the American model]. PMID- 1410896 TI - [Lipids and lipoproteins in chronic alcoholism. Outcome after alcohol withdrawal]. AB - The plasma lipids and lipoproteins changes observed in chronic alcoholic subjects and their modifications after cessation of drinking were studied in 379 patients admitted for alcohol withdrawal. The modifications were evaluated after one month (n = 348), 6 months (n = 56) and one year (n = 29) of abstinence. A significant decrease of HDL-cholesterol and apo A-I levels was noted after one year. HDL cholesterol, apo A-I and apo B showed a biphasic variation with significant post withdrawal changes which became less pronounced after 6 months of abstinence. The authors insist on the need for a prolonged post-withdrawal monitoring of plasma lipoproteins and apolipoproteins levels to evaluate the consequences of cessation of major chronic alcohol abuse. This study shows that the variations of plasma lipids and lipoproteins levels observed in heavy drinkers are similar to those observed in moderate drinkers, whereas the incidence of cardiovascular diseases seems to be higher in the former than in the latter. PMID- 1410897 TI - [Retrospective study of 594 HIV-1 seropositive patients seen in 8 hospitals of western Paris]. AB - This multicenter retrospective study concerns 594 cases of HIV-1 positive patients. The majority were asymptomatic. Some had Aids-related complex and some had AIDS. They were all seen in seven hospitals of the western outskirts of Paris and in one Paris hospital between 1983 and 1988. There was a predominance of homosexuals and of cases of AIDS in the center of Paris. Intravenous (IV) drug users and asymptomatic cases were more numerous in the city outskirts, a reflection of the populations at risk around each hospital. The proportion of cases of AIDS was lower among IV drug users than among homosexuals or bisexuals probably due to the fact that the viral infection was discovered at an earlier stage in a population contaminated at a later date or to the tendency to ask for the test "systematically" in drug addicts. 22% of the cases were women with a sex ratio of 3.5. HIV infection was attributed to use of intravenous drugs in 51% and to heterosexual transmission in 18% of the women. But the incidence of heterosexual transmission increased significantly, essentially in women. Overall, the incidence of infection by the HIV 1 has decreased since 1986. A number of recent publications seem to indicate the same tendency. But this fundamental observation remains to be validated by further studies. The yearly incidence of AIDS increases. The 5 year calculated actuarial rate of probability of remaining asymptomatic decreased to 40% in 385 initially asymptomatic patients. PMID- 1410898 TI - [Death in Horton disease. Prognostic factors]. AB - The authors reported causes of death and searched for prognosis factors in Giant Cell Arteritis (GCA). The diagnosis was confirmed by temporal biopsy in all cases. Fourteen patients died during treatment; thirty-six patients had completely recovered (follow up > 6 months after withdrawal of steroid therapy). The commonest causes of death were cardiovascular (n = 7) and digestive (n = 4); they occurred after an average of 195 days of treatment, half of them during the first three months. One death was due to GCA (autopsy) and five deaths were attributed to the treatment with corticosteroids. The prognosis factors were searched for by comparing age, sex, clinical signs, laboratory data before treatment, past medical history in the both series; further more initial dose of Prednisone and the dose after 180 days of steroid therapy were compared in the two groups. The adverse prognosis factors revealed by this study were: advanced age (p < 0.01), previous ischaemic heart disease (p < 0.05) and higher dose of corticosteroids administered at 6 months of treatment (< 0.01). PMID- 1410899 TI - [Hand disorders in pianists]. AB - During the past 10 years numerous studies have been devoted to the pathology of musicians. A few of these studies exclusively concern pianists. From a questionnaire filled and returned by 44 pianists we were able to determine the type and frequency of the symptoms encountered. Pain and stiffness are the principal symptoms, the 4th and 5th fingers being those most affected. Three pathologies predominate in the literature: overuse syndrome, entrapment neuropathy and functional dystonia. The often long and difficult curative treatment rests on rehabilitation. Training in the fundamental postures the pianists must adopt should enable them to reduce the occurrence of these pathologies. PMID- 1410900 TI - [Current aspects of paraneoplastic acute polyarthritis]. AB - Paraneoplastic acute polyarthritis (PAP) is a recognized rheumatological entity with semeiological features that are based only on a few published cases. We thought that it would be of interest to review the literature and present the current characteristics of PAP, taking into account only those cases where the acute polyarthritis and a neoplastic disease followed parallel courses. The clinical manifestations of PAP are extremely varied, making it difficult to distinguish this disease from some forms of rheumatoid arthritis, the RS3 PE syndrome or polymyalgia rheumatica. Clinicians must be vigilant when they are faced with a particularly progressive acute polyarthritis in a patient aged over 60, and particularly when this patient's general condition is altered and when fever and a clear-cut inflammatory syndrome are present. In such circumstances, it is mandatory to investigate for an underlying neoplasia. PMID- 1410901 TI - [Inflammatory neuropathies]. AB - Inflammatory neuropathy is the term used for all neuropathies associated with an inflammatory infiltrate of the nerves and/or nerve roots. Broadly speaking, there are two types of inflammatory neuropathies: those caused by an identified infectious agent, and those of uncertain origin for which an autoimmune process is usually blamed. Among the neuropathies of infective origin, leprosy is the most important owing to its frequency and to the physiopathological and therapeutic problems it still poses to clinicians and researchers, since the form and severity of nerve lesions depend on cellular immunity to the bacillus' antigen rather than on the bacillus itself. Retroviral infections, caused by the virus of AIDS more than by the virus of tropical spastic paraplegia, are responsible for numerous neuropathies the mechanisms of which are discussed here. The principal inflammatory neuropathies of uncertain origin are polyradiculitis and its different forms, and the heterogeneous group of neuropathies associated with Sjogren's syndrome. PMID- 1410902 TI - [Epidemiology and clinical aspects of imported tropical diseases]. AB - The number of people travelling of the tropical countries is in constant progression and today represents about 5% of the population of the developed countries. Mortality is mainly accidental. Morbidity essentially concerns transmissible diseases. Diarrhoeal symptoms occur in 20-55% of travellers, are bacterial in 2 cases out of 3, and can be prevented. Cholera should soon have an efficient oral vaccine. Hepatitis A is frequent in some travellers (2-3%) and can be prevented by vaccination. Hepatitis E is beginning to be observed. Strongyloidiasis can in some cases evolve to serious complications; it may be latent, so should be sought systematically after any visit to the tropics. Most affections on returning to the industrialised world concern paludism of the Plasmodium falciparum type, leading to a still high mortality rate of 400 per year in Europe, while the preventive and curative means available are sufficient. Any fever should therefore be suspected and suitable treatment given. Other causes of fever are acute viral hepatitis, typhoid fever, the arboviroses, and numerous other conditions. Dermatoses represent the third reason for consultation on returning. These mainly concern pruriginous symptoms with filariases and abnormal hosts being evidenced. Furunculous lesions indicate a diagnosis of cutaneous leishmaniosis or myases. Any form of pruritus should suggest a diagnosis of HIV infection, or pruritus should suggest a diagnosis of HIV infection, or particularly trypanosomiasis. The risk of sexually transmissible disease is overall 6-fold higher in tropical travellers; advice before travelling is therefore of paramount importance. Should a seropositive subject travel to the tropics?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410903 TI - [Destructive polyarthritis in Behcet's disease. Apropos of a case and review of the literature]. AB - The authors report a case of a 37 years old man with Behcet's disease since 7 years who develops a destructive chronic polyarthritis involving wrists, hands and one knee. The parallel evolution between recurrent orogenital ulceration and arthritis added to the absence of other associated destructive rheumatism permit to link this polyarthritis to Behcet disease. In spite of the few reports, the occurrence of destructive arthritis can't exclude absolutely the diagnosis of this affection. PMID- 1410904 TI - [Gorham disease disclosed by pathological fracture]. PMID- 1410905 TI - [Extensive pharyngeal necrosis: an unusual complication of dermatomyositis]. AB - To our knowledge, the occurrence of extensive pharyngeal necrosis in patients with dermatomyositis has not yet been reported. We report such a case characterized by a vast ulceration of the posterior laryngeal wall, extending from the velum palati to the larynx and responsible for both dysphagia and dysphonia. Treatment with an immunosuppressant had no effect on the lesions. PMID- 1410906 TI - [Double heart valve replacement disclosing antiphospholipid syndrome]. AB - In patients with systemic lupus erythematosus (SLE) heart valve lesions are usually discovered at echocardiography; their haemodynamic repercussions are uncommon, and valve replacement is exceptional. We report the case of a woman who had undergone aortic and mitral valve replacement before antiphospholipid antibodies were found associated with 4 ARA criteria of SLE. Histopathological examination confirmed the diagnosis of Libman-Sachs specific endocarditis. The presence of antiphospholipid antibodies leads to a discussion of their role in the physiopathology of the heart valve lesions and vascular accidents that occurred in this patient. The overlap observed between the diagnostic criteria of SLE and those of primary antiphospholipid syndrome is discussed. Heart valve lesions may be one of the modes of access to the antiphospholipid syndrome. PMID- 1410907 TI - [Prophylaxis of malaria]. AB - The prevention of malaria is based on chemoprophylaxis and protection against the vector. Nocturnal mosquito bites can be avoided by individual and collective measures, while chemoprophylaxis involves the use of various agents according to the place and duration of stay. Three endemic zones can be defined on the basis of chemoresistance. Chloroquine, proguanil and mefloquine are the three drugs used in this setting, the latter being contraindicated for pregnant women and children. Travellers making long stays in areas of low-level chemoresistance and short stays in areas of high-level resistance and for whom mefloquine is contraindicated are advised to take antimalarial drugs at the first signs of potentially malarial fever when medical care is unavailable. Quinine, halofantrine and mefloquine are used for the curative treatment of malaria in areas of chloroquine resistance. PMID- 1410908 TI - [Osteolytic metastases of breast cancer and biphosphonates]. AB - Three-quarters of breast carcinomas at an advanced stage display metastases, usually of the osteolytic type. Osteolysis results from a predominant increase of osteoclastic activity stimulated by humoral or local factors secreted by cancerous cells. Bisphosphonates interfere with osteoclasts and therefore can reduce the osteolysis. These compounds act through three main mechanisms: physico chemical inhibition of bone crystal, cytostatic effect on osteoclasts, and in the case of pamidronate, direct or indirect action on the mononucleate precursors of osteoclasts. Three bisphosphonates are now available: etidronate, clodronate and pamidronate. Ten published studies report on their use in breast carcinoma with osteolytic metastases, and without hypercalceamia. Four studies concern clodronate in 54 patients, and six studies concern pamidronate in 128 patients. Intravenous pamidronate seems to be the more effective of the two, with densification of the lytic areas in 25% of the cases. All studies mention a decrease of pain, risk of fracture, hypercalcaemia and new metastatic locations. Side-effects are minimal. Controlled studies are needed to confirm the position of bisphosphonates in the management of malignant osteolysis. PMID- 1410909 TI - [Mediastinal adenopathies and myeloma]. PMID- 1410910 TI - [Hepatotoxicity of cyproterone acetate]. PMID- 1410911 TI - [Case reports of the Kummel-Verneuil syndrome]. AB - The significance of the complex clinical-radiological diagnosis is demonstrated in three cases of the Kummel-Verneuil syndrome, the bone scintigraphy allows the demonstration and localisation of the bone process, but in respect to the differential diagnosis the results are unspecific. The CT allows an early and sure demonstration of the intravertebral vacuum phenomenon. In patients with nonspecific vertebral fractures the quantitative determination of the mineral content of the vertebral bones is indicated. The therapeutic decision is determined by the necessity of the biomechanical stabilisation. PMID- 1410912 TI - Recurrent benign retroperitoneal lipoma. AB - A case of a rare recurrent lipoma originating from the perirenal fat is reported. Onset of symptoms (abdominal pain, weight loss, appetite loss, abdominal swelling, nausea, constipation) is late and the treatment is surgical, but postoperative radiation or chemotherapy may be indicated. Ultrasound, CT and NMR scans, pyelograms and barium enemas are the most important diagnostic investigations. Follow-up in these patients is important. PMID- 1410913 TI - [Cancer of the cervix uteri in young people]. AB - The age-group distribution, risk factors, histopathological aspects, diagnosis, treatment and prognosis of 111 diagnosed and/or treated cervical carcinomas in women aged up to 40 years out of 478 cases with the same diagnosis were reviewed. It is considered that the incidence of 23.2% in this series is situated at the extreme of the high frequencies reported in the literature. Nineteen per cent of the cases were diagnosed in stages O and Ia, a well organize program for early detection being required. In our series, the 5-year survival rate was 73.3%. This finding, although in a small series of cases, supports the opinion that age has no influence upon the prognosis of this disease. PMID- 1410914 TI - [The use of cell cultures in the cytotoxicity testing of dental materials]. AB - On lines of human (HeLa) and monkey (BS-C-1) cell cultures, the cytotoxicity of 15 products of dental use for radicular and coronary fillings, alloys and endodontic antiseptics was analysed. It was found that the simplified method can be used, together with the in vivo and in vitro tests recommended by I.S.O., for determining the bioavailability of dental products. PMID- 1410915 TI - [Viral hepatitis C: new epidemiological horizons]. PMID- 1410916 TI - [Painters, drawers and engravers with medical themes (IV)]. PMID- 1410917 TI - [Acute nosocomial bacterial meningitis. Apropos 27 cases]. AB - Our series includes 27 patients with nosocomial meningitis (22 post neurosurgery and 5 post spinal puncture) of whom 15 with stated etiology (gram-negative bacilli and staphylococcus aureus in equal shares). Under the treatment with chloramphenicol + rifampicin + gentamicin a cure was obtained in 22 cases, improvement in 3 cases and 2 patients died. PMID- 1410918 TI - The timing of violence amongst psychiatric in-patients. AB - The timing of violence among psychiatric in-patients with reference to the time of day, day, month and season over a four-year period were studied. Most of the violence occurred in the daytime. There was no daily variation, but there were spring and summer peaks of violence. The implications of these findings on staffing discussed. PMID- 1410919 TI - [The involvement of biologically active lipids in cardiovascular pharmacotherapy]. PMID- 1410920 TI - [Biological markers in the precise diagnosis of chronic alcoholic intoxication- the significance of blood changes]. AB - The frequency of some blood disturbances during chronic alcoholism determined us to extend the biological investigations of alcohol abuse effects on blood figurated elements and hemostasis. The investigation of some series of alcohol addicts revealed clear-cut differences, directly proportional with the quantity and length of intoxication. The obtained results certify a disordered hemostasis, insufficiently elucidated as a possible biological cause of alcoholic states, manifested by alterations of some humoral elements in various forms of chronic alcoholism with mental disturbances. PMID- 1410921 TI - [A microepidemic of severe tuberculosis in a hospital for chronic neuropsychiatric patients]. AB - Details and considerations on a microepidemic of severe tuberculosis occurring in a hospital for chronic neuro-psychic patients are presented. This episode presents a practical interest by the knowledge of the circumstances of occurrence and progression, clinical-epidemiological features, associated favouring factors (immunodeficiency, absence of a sustained program for tuberculosis investigation) and biologic prophylaxis by BCG vaccinations and revaccinations. Several measures for avoiding such epidemics and, in prospect, of AIDS in the institutions at high risk are discussed. PMID- 1410922 TI - [Ticlopidine and its use in therapy]. PMID- 1410923 TI - [The evaluation of the nitrate and nitrite content of meals in Moldova]. AB - Between 1986 and 1990 the content in nitrites and nitrates of the daily meals in various collectivities in Moldavia was determined. The nitrite content ranged between 1.3 mg. NO2-/day (Suceava) and 7.38 mg NO2-/day (Botosani) and the nitrate content between 24.93 mg NO3-/day (Suceava) and 92.30 mg. NO3-/day (Galati). The content in these poisons of the daily meals in two creches from Iasi and Bacau was also analysed, high values for both of them being found in the Bacau creche. Some measures are suggested. PMID- 1410924 TI - [The interpretation of the telomic distribution of the pulmonary arterial trunk]. AB - The analytical study of the periodicity of organic processes is of great interest as reflected by the literature. This paper aims at describing the functional implications from the viewpoint of pulmonary functional arterial circulation regularity. In the light of morphological aspects, the pressure falls along a symmetric telomic tree were followed up and compared with the experimentally obtained data. PMID- 1410925 TI - [Pharmacological studies of sulbactam and its association with semisynthetic beta lactam antibiotics]. AB - The acute toxicity, local tolerance and pharmacokinetic properties of sulbactame manufactured by the Iasi Antibiotic Investigation Centre, alone or in association with ampicillin or amoxicillin were tested. Some tests were made comparatively with the product Unasyn--Pfizer. The obtained data show that this beta-lactamase inhibitor has a low toxicity--DL50 i.p. in mice over 4,000 mg/kg, both alone or associated with the two semisynthetic beta-lactamic antibiotics. The local tolerance is good and the serum levels of the above mentioned associations are above towards the tested bacteria and are similar or very close to those of Unasyn. It is believed that the therapeutical use of the association sulbactame + ampicillin or sulbactame + amoxicillin is very useful in the beta-lactamase producing germs infection. PMID- 1410926 TI - [The physicochemical characterization and therapeutic evaluation of Cicatrol]. AB - Cicatrol ointment with the formula: argentic sulphamethoxydiasine 1 g, bentonite hydrogel 12.5% for 100 g is manufactured at the Microproduction Laboratory of the Faculty of Pharmacy of Iasi. The one-year physicochemical determinations of the aspect, colour, homogeneity, pH, rheological behaviour and relative viscosity, content in argentic sulphamethoxydiasine as well as "in vitro" antimicrobial activity of Cicatrol showed a good stability and gel properties enabling an uniform and long-term contact with the wound. The clinical investigations carried out until now in patients with burns, varicose ulcers, trophic shank ulcers, superficial phlebitis with atonic ulcerations or wounds with multiple sites revealed its remarkable therapeutic value. As compared to other similar products, Cicatrol by its aseptic properties favours the scarring of any type of wound, a normal skin, without keloid scars being obtained, it also being well tolerated. PMID- 1410927 TI - [The quality assessment of a product with adhesive properties for complete dental prostheses]. AB - A formula of dental adhesive using as an agent responsible for this activity an indigenous product, C.M.C.Na 1080, gelified with preservative solution with added astringent agents was elaborated. The possible interaction between the constituents during preservation and the product qualities by determining the pH, extensibility index, sliding limit tension, antimicrobial activity and certain clinical aspects were evaluated. PMID- 1410928 TI - [Phthalazinilides. The action of ethyl bromopyruvate on phthalazine]. AB - Our investigation for obtaining carbon-nitrogen stable ilides continued by the synthesis of new phthalazinic derivatives by the action of ethyl brompyruvate. The structure of the obtained products was confirmed by chemical and spectral analyses. The results regarding their antimicrobial action are also presented. PMID- 1410929 TI - [Our experience in the conservative surgical treatment of coxarthrosis]. AB - The authors present the substantiation of the use of conservative treatment in a series of 163 patients with coxarthrosis operated upon between 1983 and 1990. In 135 of these patients various types of osteotomies were performed: Pauwels valgisation or varus femoral osteotomy (42 cases), McMurray displacement osteotomy (41 cases), varus and displacement osteotomy (19 cases) and Chiari pelvic osteotomy (33 cases). In the remainder of 28 patients tenotomies and hip denervations were performed. The postoperative results, estimated by a strict clinico-radiological survey revealed a marked clinical improvement and radiographically a restoration of joint congruence in about 80% of the cases. PMID- 1410930 TI - [Research trends in the field of toxicology in Iasi (1964-1991)]. PMID- 1410931 TI - [Dento-periodontal interferences in extended partial anodontia]. AB - In this paper, part of a mixed longitudinal study on the growth and development phenomena in extended partial anodontia, the author, based on the data of the thorough clinical and paraclinical investigations carried out, underlines the implications of this isolated dental anomaly on temporary or impacted permanent teeth as well as on their periodontal support. Thus, 48 patients aged between 4.6 and 30.5 years with various clinical forms of extended partial anodontia were investigated. It resulted that the severity of the dental-periodontal involvement is strongly correlated with the etiopathogenic and clinical features and severity of the anomaly under study. PMID- 1410932 TI - [Lyme disease]. PMID- 1410933 TI - [The psychopathological risk factors in chronic alcoholism]. PMID- 1410934 TI - [The involvement of eicosanoids in reproduction (II)]. PMID- 1410935 TI - [Situational psychiatric understanding of the genetic contribution (I)]. PMID- 1410936 TI - [A iatrogenic manifestation: the neuroleptic malignant syndrome]. PMID- 1410937 TI - A new methyl bromide gas generator for inhalation toxicity studies. AB - A simple generator for methyl bromide gas has been newly developed by us. For inhalation toxicity studies, until now, there have been few generators capable of producing a constant and stable concentration of methyl bromide gas easily because of its high volatility. The principle of this new generator is based on gas-liquid equilibrium. The gas is generated from the surface of liquid methyl bromide in an evaporator made of a Teflon tube. The generator can produce up to 10,000 ppm of methyl bromide gas in a 0.1 m3 exposure chamber, and the concentration of this generated gas is able to be kept within +/- 0.8% over a long period of time. The generator has proved to be useful for investigating the effects of methyl bromide on health in inhalation toxicity studies. PMID- 1410938 TI - Ethnic differences of the primary gene defect at the cytochrome P-450 2D6. AB - The cytochrome P-450-dependent monooxygenase system is involved in the metabolism of both endogenous compounds and xenobiotics. The role of these enzymes in toxicological response is exemplified by an autosomal recessive polymorphism at the cytochrome P-450 2D6 debrisoquine-4-hydroxylase locus, which results in the severely impaired metabolism of many drugs [Gough et al. (1990) Nature 347: 773 776]. The prevalence of this polymorphism (poor metabolizer) differs considerably between ethnic groups. Here we analyzed the P-450 2D6 polymorphism in 25 Japanese and 20 Chinese by DNA-based genetic assay using peripheral leukocyte. Although the phenotype of all the normal metabolizers and 79% of the poor metabolizers could be identified in Caucasians, this DNA-based genomic assay could not predict poor metabolizers in both the Japanese and Chinese. These results indicate that the genetic mechanism of the phenotyped poor metabolizer in Orientals is different from that in Caucasians. PMID- 1410939 TI - [Studies on purine-pyrimidine metabolism (1)--Quantitation of purine-pyrimidine metabolites and allopurinol-oxipurinol in biological fluids]. AB - A reversed-phase high-performance liquid-chromatography method for determining simultaneous quantitation of purine-pyrimidine metabolites, allopurinol and oxipurinol in plasma and urine samples was studied. Separation was optimal with phosphate buffer (10 mmol/l, pH 5.0) containing 1% methanol as an eluent and mu Bondapak C18 as a column. An isocratic separation of a standard mixture of 13 compounds was achieved within 40 minutes with adequate reproducibilities (coefficient of variation: 2.49% for 1.63 mumol/l orotidin-0.12% for 50 mumol/l uridine). A simple ultrafiltration of plasma yielded quantitative recoveries (uric acid: 101.7-107.5%, hypoxanthine: 90.4-102.8%, xanthine: 95.9-99.5%, oxipurinol: 104.4-107.1%, allopurinol: 97.4-103.4%). Compounds were identified by their retention times, absorbance ratios, co-elution with standards and enzymic shifts. In addition to the above compounds, simultaneous quantitation of pseudouridine, uridine, adenine and inosine in the plasma would be possible under the same conditions. PMID- 1410940 TI - [A descriptive epidemiology on sudden death among workers]. AB - A survey on sudden unexpected death, that is, death within 24 hours from acute onset, among Japanese workers was carried out. Questionnaires were sent to full time occupational health physicians who were active members of the Japan Association of Industrial Health at the time of the survey. Though 241 doctors answered (response rate: 61.5%), only 53 of them who had had both sudden death cases and the desire to join in this research co-operated in this survey. During the 5 years of observation (from Jan. 1, 1986 to Dec. 31, 1990), 143 cases of sudden death, 141 males and 2 females, were reported. The mean age was 46.5 (S. D. 10.5) for males. The ages of the 2 females were 31 and 44. Onset took place most frequently at home (55%) and most often during sleep (26%). This may be due to the higher rate not only of onset but of death resulting from acute onset at home and during sleep. Similar to the previous findings, a small peak of incidence was found early in the morning (4:00 AM--9:00 AM), although this was not statistically significant. However, the weekly and seasonal variations were a little different from previous reports. In this study, sudden death tended to occur more on Monday, Thursday, Friday, and Saturday (not statistically significant), and as for the seasonal variation, more cases occurred in April, November, and December which were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1410941 TI - [X-ray examination of the gastrointestinal tract in systemic cutaneous disease]. AB - An X-ray examination of the gastrointestinal tract was performed on 56 patients with systemic cutaneous disease that is often considered associated with internal malignancies. Found were one case of esophageal cancer, two cases of gastric cancer, and two cases of colon cancer. The prevalence of gastric and colon cancer in these patients showed a statistically significant increase compared to the general population. The rate of gastric cancer was 16.26 times higher than the general population and that of colon cancer 32.26. X-ray examination of the gastrointestinal tract in patients with systemic cutaneous disease is useful for detecting malignancy. PMID- 1410942 TI - [Cutaneous thermal-cooling and -warming detection thresholds in distal extremities of normal subjects]. AB - The cutaneous thermal-cooling and -warming detection thresholds were evaluated on the dorsal side of the right distal forearm and on the dorsum of the right foot in 134 normal subjects (66 men and 68 women) without sensory symptoms and signs, aged from 11 to 87 years by using a Thermal Threshold Tester (Vickers Medical International, England). The normative data for the clinical evaluation of the severity and the pathologic process of the sensory disturbance of the patients were obtained. The data obtained included 1) the mean of each threshold and 2) its upper limit value of 95% confidence interval for each decade. The mean of each threshold was significantly increased with aging (P less than 0.0001). Therefore, the cutaneous thermal-cooling and -warming detection thresholds of the patients with sensory disturbances should be compared with the normative data adjusted for the age of each subject obtained in this study. Based on the evaluation, repeated six times for three weeks, of each threshold of six volunteers (ages from 21 to 66), high reliability of each threshold (intraclass correlation coefficient from 0.78 to 0.96) was observed. PMID- 1410943 TI - Current status of education and training in occupational health and their development programs in China. AB - There are 40 post graduate schools of public health in China, from where 1,400 students are graduating every year. Fourteen percent of them are going into occupational health field. A total of about 25,000 specialists are now working in the occupational health field. However, this number is only 1 percent of all health workers in China. Facts on the educational resources in China including responsible institutions and programs for such occupational health specialists are introduced and discussed. Finally a program for increasing the number of occupational health specialists in the Eighth Five-year Plan of China is introduced. PMID- 1410944 TI - Humanism in medicine. Benevolence or realism? PMID- 1410945 TI - What does a human relationship with the doctor mean? AB - Previous studies have demonstrated that the human relationship with the doctor is very important. The aim of this study was to describe the specific behaviour in consultations where the patient experiences a satisfying human relationship with the family doctor. 46 consultations with 12 participating general practitioners were video-taped in four health care centres. Afterwards the patients and the doctors, on different occasions, commented on the recorded consultations. The comments were audio-taped. Those comments of the patients which dealt with human relationship to the doctor were analysed. The sequences in the videotaped consultations just before these comments were transcribed and analysed. The study demonstrated that the concrete meaning of human relationship deals with simple and obvious things. The patients want the doctor to take their symptoms seriously; to listen and/or ask questions about the symptoms, and to treat the patient as a real person, not only a patient; to ask questions about other things than the disease, e.g. about the patient's family or work. PMID- 1410946 TI - A controlled, multicentre trial of manual therapy in low-back pain. Initial status, sick-leave and pain score during follow-up. AB - 101 outpatients with acute or subacute low-back pain were randomly allocated to one of two treatment groups. One group was given standardized conventional but optimal activating treatment by primary health care teams. The other group received manual treatment such as manipulation, specific mobilization, muscle stretching, auto-traction, and cortisone injections. The two groups were similar in most of the pretrial variables, including age, sex, previous low-back pain problems, sick-leave, previous treatment, findings at the physical examination, quality-of-life score, disability rating, and pain score. After one month in the study, the proportion of patients on sick-leave was six times larger in the conventionally treated group than in the group receiving the specific manual treatment. The difference diminished over time but was still significant after eight months. Two slightly different pain scores ("pain at the moment" and "pain during the last weeks"), initially similar in the two groups, diminished in both groups but were significantly lower in the manual treatment group during the study. The group receiving specific manual treatment thus had a significantly better outcome than the group receiving conventional treatment as far as sick leave and pain score are concerned. PMID- 1410947 TI - General practitioners' attitudes to oestrogen prescription in the menopause: a national survey in Norway. AB - A questionnaire was mailed to a random sample of approximately 10% of Norwegian general practitioners (GPs) in order to investigate attitudes to the prescription of hormone replacement therapy (HRT) in menopausal women. Nine short case histories were presented, and the GPs indicated their attitude to oestrogen prescription in each case on a five-step scale. Each case history contained four items that were systematically varied so that the effect of each could be investigated by comparing the answers from case to case. 251 GPs (74%) responded to the questionnaire. The answers indicated restrained attitudes towards prescription of HRT. Smoking and a family history of cardiovascular disease were regarded as contraindications. Angina pectoris was considered a contraindication for local oestrogen application in elderly women with urogenital complaints. PMID- 1410948 TI - Predictive validity of factors influencing the institutionalization of elderly people with psycho-geriatric disorders. AB - The predictive validity of certain items was tested with respect to their influence on the institutionalization of elderly people with psycho-geriatric disorders (n = 69). Twelve items measuring both the patient's condition and the exhaustion around the patient were tested. Two outcome measurements were used, the first measuring the number of patients who were institutionalized after the end of 12 months and the second measuring the number of days at an institution during 12 months. The items "Exhaustion of spouse" and "Supervision need" showed the highest correlation with institutionalization and predicted institutionalization, better than items describing the degree of dementia. PMID- 1410949 TI - Screening of an elderly population in primary care for primary hyperparathyroidism. AB - In order to assess the diagnostic outcome of a screening for primary hyperparathyroidism (PHPT) in an elderly population, we determined ionized calcium in serum from 368 individuals participating in a health control at Molnlycke Primary Care Centre (200 women, 168 men; age range 75-95 years); four fifths of the individuals living in their homes, the remainder in homes for aged or nursing homes. Intact parathyroid hormone was determined in the samples with oinized calcium concentration greater than mean + 3SD of the truncated population sample, and these individuals were also recalled for another blood sample. Moderate hypercalcaemia, probably due to PHPT, was found in eight individuals (2% of the complete sample, 3% of the women), five having neuropsychiatric or neuromuscular symptoms consistent with PHPT. Surgical intervention is probably indicated in only a small proportion of elderly patients. We conclude that optimal benefits in relation to costs of screening for PHPT in old people will depend on the availability of a safe and simple pharmacological treatment that could determine any causal relationship between hypercalcaemia and symptoms. PMID- 1410950 TI - The Butajira rural health project in Ethiopia: epidemiological surveillance for research and intervention in primary health care. AB - Ten study populations sampled from a total of 86 communities in a rural Ethiopian area, have been registered and followed for a period of four years. A baseline census revealed a median age of 15 years, a literacy rate of 24%, poor housing and environmental conditions, and low utilization of the existing health care facilities. A surveillance system was established which made it possible to estimate the occurrence of vital events. This showed a crude birth rate of 40.3/1000, a crude death rate of 16.4/1000, a life-expectancy at birth of 48 years, an infant mortality rate of 114/1000, a yearly child (1-4 years) mortality rate of 36/1000, and an under-five mortality rate of 210/1000. The implications of these data in terms of the planning and operations of research and health services are discussed, and on-going and projected studies are outlined emphasizing the methodological potentials of this epidemiological study base. PMID- 1410951 TI - Recruitment and participation of general practitioners in a multipractice study of smoking cessation. AB - In May 1986, all 398 general practitioners (GPs) in western Norway were invited by letter to take part in a multipractice intervention study of smoking cessation among pregnant women. The aims of the intervention study were: 1) to find out how a smoking cessation model can be implemented in ordinary consultations in general practice, and 2) to compare smoking cessation in pregnant and non-pregnant women. The intervention study lasted for three years. 187 (47%) GPs completed the study. Working in a group practice, working on regular salary, having started specialization in general practice, being less than 40 years of age, and being a non-smoker were significantly more common among the participating GPs. They also had significantly fewer consultations per week than their non-participating colleagues. A stepwise multiple logistic regression analysis revealed that smoking habits predicted participation in the study far more than any other predictor. PMID- 1410952 TI - Urinary incontinence in women and the effects on their lives. AB - The aim of this study was to assess and analyse the effects of urinary incontinence in women and to examine the relationship between these effects and the type and severity of incontinence. 110 women aged 20 to 65 who had reported urinary incontinence to their general practitioners underwent a comprehensive history and a complete urodynamic evaluation. The reported consequences of incontinence included low self-esteem, changing life-style in order to avoid potentially embarrassing situations, and all kinds of practical worries. Fear of the odour played the most important part and was mentioned as being the worst effect in 40% of the cases. Most of the women appeared to cope adequately with the unpleasant aspects of this condition. More effects were associated with urge incontinence than with stress incontinence, while there was a significant relationship between the objective severity of the incontinence and its psychosocial impact. The main conclusion is that although urinary incontinence is not a severe physical disability, a spectrum of psychological problems is associated with it. In particular, the fear of being smelt was of the utmost importance. PMID- 1410953 TI - Intervention in alcohol abuse among macrocytic patients in general practice. AB - The study examined the effectiveness of routine intervention in alcohol abuse by a general practitioner, with help of a laboratory test. Patients diagnosed as abusers because of high erythrocyte mean cell volume value (MCV) and having no other cause for it were randomly allocated to two groups: 1) an intervention group, comprising 92 patients (69 men and 23 women), who were invited for follow up at three-monthly intervals for a year; 2) a control (mini-intervention) group, 86 patients (71 men and 15 women), who were followed-up only after 12 months. Follow-up attendance was poor, particularly in the intervention group. In general, MCV-values were unchanged in the groups at the end of the study, though there was a clear trend for the female controls to have lower values (101.9 fl at the start, 98.5 fl at the end, p = 0.06). Altogether 11% (4/38) of the women and 7% (10/140) of the men had clearly reduced their alcohol consumption after one year, and this was also seen in their MCV-values. Mini-intervention, especially in women with an abnormal laboratory value, seems to be, with the help of MCV, at least as effective a way of counselling nonalcoholic abusers as a more systematic intervention. PMID- 1410954 TI - An evaluation of a commercial co-agglutination test for the diagnosis of group A streptococcal tonsillitis in a family practice. AB - The result of a rapid co-agglutination test was compared with the clinical diagnosis of group A streptococcal tonsillitis, a laboratory culture from the throat serving as the correct result. The study was carried out in a family practice, with two GPs partaking: it included 105 consecutive patients. The outcome of the rapid test was significantly correlated to the degree of growth determined by throat culture, and it was superior to the clinical judgement. The statistical analysis of the results of the rapid test revealed (95% confidence limits in brackets) a specificity of 97% (91-100), sensitivity of 68% (48-84), a positive predictive value of 90% (70-99), and a negative predictive value of 89% (81-95). Although the co-agglutination test was superior to the clinical diagnosis, the sensitivity of this test is rather low when compared with other recently evaluated rapid tests for use in family practice. PMID- 1410955 TI - Diagnosis of pneumonia in adults in general practice. Relative importance of typical symptoms and abnormal chest signs evaluated against a radiographic reference standard. AB - The diagnostic value of typical symptoms and abnormal chest signs for pneumonia have been evaluated against a radiographic reference standard in 402 adult patients with respiratory tract infection in general practice. Pneumonia was diagnosed in 20 patients by a positive chest radiograph. The doctors diagnosed pneumonia in seven of these on the basis of history and physical examination alone, and in addition in 22 patients with normal radiographs. The diagnostic value of the typical symptoms cough, chest pain, and dyspnoea, reported by the patients on a questionnaire, increased with increasing intensity of the symptoms, and both "very annoying lateral chest pain" and "very annoying dyspnoea" had likelihood ratios (LR) between 4 and 5. The LR of crackles was 3.7. When evaluated against the doctor's clinical diagnosis of pneumonia as reference standard, crackles achieved an LR of 14.8, while the typical symptoms achieved lower LRs than when evaluated against the radiographic reference standard. These discrepancies, which were confirmed by logistic regression, indicate that crackles and other abnormal chest findings are interpreted too frequently as features of pneumonia and that the importance of typical symptoms is underestimated in the diagnosis of pneumonia. PMID- 1410956 TI - Laboratory tests for pneumonia in general practice: the diagnostic values depend on the duration of illness. AB - The usefulness in the diagnosis of pneumonia of temperature and the laboratory tests: erythrocyte sedimentation rate (ESR), leucocyte count, and C-reactive protein (CRP) was evaluated against a radiographic reference standard in 402 adult patients with respiratory tract infection in general practice. Radiographic pneumonia was diagnosed in 20 patients. CRP and ESR were the most useful tests. CRP greater than 50 mg/l had lower sensitivity and likelihood ratio (LR), 0.50 and 4.8, respectively, compared with previous studies of selected patient populations. Among patients whose duration of illness exceeded six days the corresponding LR was 11.3, due to a higher specificity in this subgroup of patients. ESR and oral temperature were also more useful in this subgroup than in patients with a shorter duration of illness. A highly significant diagnostic contribution of adding ESR and CRP to history and physical examination, particularly when the illness had lasted one week or more, was demonstrated by logistic regression. PMID- 1410957 TI - The changing geographical coherence of measles morbidity in the United States, 1962-88. AB - Geographical coherence may be defined as the degree to which the behaviour of a time series in one geographical area corresponds with the time series behaviour in another. This paper illustrates the concept using the epidemiological time series of reported monthly measles morbidity for the states of the United States for the 27 years from January 1962 to December 1988. Over this period, as measles morbidity has declined in response to vaccination campaigns, and as the seasonal peaking of the disease in late spring has become less pronounced, the geographical coherence has altered at the national, divisional, regional and state levels. There was a steady decline in coherence from 1962 to 1980. In 1981, a dramatic reduction occurred, but there has been some recovery since. The implications for spatial forecasting models of these reducing levels of coherence are discussed. PMID- 1410958 TI - Short and medium term projections of the AIDS/HIV epidemic by a dynamic model with an application to the risk group of homo/bisexual men in Amsterdam. AB - Several methods exist for short term projection of the numbers of AIDS cases. Some use extrapolation of empirical curves fitted to data up to a given time, whereas others such as the popular method of 'back projection' or actuarial methods also use information about the process. In this paper we describe a dynamic model based on a distributed modelling technique allowing for variability both in infectiousness and in age distribution of the population at risk. Some model parameters are taken from the literature, others are estimated from AIDS incidence data from the homo/bisexual population in Amsterdam. The model described here simulates prevalence and incidence of HIV infection. We present prediction intervals for two years from January 1990 onwards. We discuss three scenarios based on the estimated model, two of which consider early treatment with anti-viral drugs. Given the model and the state of the epidemic in Amsterdam, early treatment intervention must be combined with very drastic measures for reducing infectivity in order to have any serious impact on the course of the epidemic. PMID- 1410959 TI - Analysis of disease risks using ancillary risk factors, with application to job exposure matrices. AB - Epidemiological studies of disease can make use of ancillary risk-factors, acquired from individuals outside the disease study. For example, several disease studies might use the same job-exposure matrix to quantify risks due to occupational exposure to industrial agents. We construct a graphical model to combine a logistic regression disease model with models for the ancillary data and the risk-factor distribution in the population. We estimate the graphical model using Gibbs sampling, and in simulations compare it with methods of direct substitution into logistic regression. PMID- 1410960 TI - Methods for comparing cumulative hazard functions in a semi-proportional hazard model. AB - Graphical methods based on the analysis of differences between log cumulative hazard functions are considered for a two-group semi-proportional hazard model which allows for interaction between treatments and covariates. Confidence procedures and test statistics that can be used to test for interaction and for main effects are developed. Their use is illustrated by applying them to the analysis of kidney transplant data from the University of California, San Francisco. PMID- 1410961 TI - Evaluations of methods for statistical surveillance. AB - The needs for statistical surveillance in different areas of medicine are described. The predictive value of an alarm and other measures for the evaluation of alarm procedures are suggested. The measures are used to evaluate some common methods of continual surveillance of time series. It is demonstrated that some methods have about the same properties at the start of the surveillance period as later. This is however not the case for all methods. For some methods the consequence of an early alarm should be quite different from that of a late one. PMID- 1410962 TI - Sensitivity and specificity for correlated observations. AB - A general estimating equation approach is used to obtain estimates of sensitivity and specificity when the data consist of correlated binary outcomes. First order approximations to the variances of estimated sensitivity and specificity for prospective and retrospective studies are given. Data from a dental study are used to motivate and illustrate the methods. PMID- 1410963 TI - A goodness-of-fit approach to inference procedures for the kappa statistic: confidence interval construction, significance-testing and sample size estimation. AB - We propose a new procedure for constructing a confidence interval about the kappa statistic in the case of two raters and a dichotomous outcome. The procedure is based on a chi-square goodness-of-fit test as applied to a model frequently used for clustered binary data. The procedure provides coverage levels that are accurate in samples of smaller size than those required for other procedures. The procedure also has use for significance-testing and the planning of corresponding sample size requirements. PMID- 1410964 TI - On the sample size for studies based upon McNemar's test. AB - When computing the sample size for studies using McNemar's test, one needs to know the probability of discordance and the odds ratio to be detected. In many studies, the investigator is unable to specify the probability of discordance, but can state, at least approximately, the marginal probabilities of each variable. This information leads to restrictions on the possible values of the cell probabilities and provides a range of admissible values for the off-diagonal cells. We compute the sample size needed in these circumstances and compare them to the results cited by Schlesselman and Connett et al. These sample sizes for the method are quite close to those found in the Monte Carlo study of Connett et al. PMID- 1410965 TI - The standard error of Cohen's kappa by J. Barry Garner, Statistics in Medicine, 10, 767-775 (1991) PMID- 1410966 TI - [Multiple neoplasms: etiological problems and possibilities for prevention]. AB - The authors present a review of the literature concerning multiple malignancies in a single patient. They emphasize etiological aspects and possible preventive strategies in a clinical entity which appears to be recognized with an increasing frequency. PMID- 1410967 TI - [Pelvic venous compression syndrome: description of a case and literature review]. AB - A case of a genuine common iliac vein compression (Cockett's syndrome) is reported. From review of the literature, it appears that the treatment should be essentially medical. Surgery is indicated in case of severe post-thrombotic sequellae. PMID- 1410968 TI - [Fetal alcohol syndrome]. AB - Ethanol teratogenicity manifests itself in the form of the foetal alcohol syndrome (FAS). This syndrome is characterised by growth delay, impairment of the central nervous system, and various facial dysmorphisms. We report the case of a 19 month-old boy affected by FAS. In addition to the three common features of FAS, this patient disclosed organic (digestive and cardiac) malformations and cellular chemotaxis deficiency. We have reviewed the literature to provide an update on the clinical signs of FAS. The abnormalities provoked by foetal exposure to ethanol can be very varied, none of them being specific. PMID- 1410969 TI - [Primary hyperoxaluria type 1, peroxisomal disease: therapeutic consequences]. AB - On the occasion of a combined liver-kidney graft doing well after 3 years, the molecular anomalies responsible for primary hyperoxaluria type 1 are discussed. This rare condition may be listed in the expanding group of hereditary diseases involving peroxisomes, cellular organelles with increasingly recognised functions. Recent progress in the molecular biology of this disease have led to the proposal of of new transplant strategies for its cure. PMID- 1410970 TI - [Accidentally discovered vascular abnormality]. PMID- 1410971 TI - [Attempt at restoration of the glucose-insulin regulation loop in the patient with insulin-dependent diabetes]. PMID- 1410972 TI - [Laparoscopy in 1992. A 37-year experience]. PMID- 1410973 TI - [The ozone hole and its impact on chronobiology. Are we directly concerned?]. PMID- 1410974 TI - [Action of drugs on the glucose-insulin regulation loop]. PMID- 1410975 TI - [Importance of fetal cardiac rhythm monitoring at home in the follow-up of pregnancies at risk: evaluation following 2 years of utilization]. PMID- 1410976 TI - [What is your roentgen diagnosis? Acute peptic ulcer of the duodenal bulb with perforation]. PMID- 1410977 TI - [Problems and changes in education exemplified by cholecystectomy]. PMID- 1410978 TI - [Subcutaneous apomorphine infusion in the treatment of Parkinson disease]. AB - Apomorphine, a dopamine-agonist was applied as s. c. infusions to 7 patients with idiopathic Parkinson's disease. The indications were longlasting akinetic episodes (4 patients) and therapeutically resistant invalidating motoric fluctuations ("on-off") as well as hyperkinesia (3 patients) on anti-Parkinson medication. The effect of apomorphine as an anti-Parkinson therapeutic was verified using clinical scales and a portable activity-monitoring device. The s. c. infusion therapy (20-90 mg/die, or 0.025-0.01 mg/kg/die respectively) was effective in the akinetic patients interrupting akinesia and the inability to swallow. An improvement was also registered in patients with "on-off" and hyperkinesia using longlasting subcutaneous apomorphine infusions. The therapy was continued over a longer period of time with 2 patients as outpatients. The side-effects were nausea and local subcutaneous indurations at sites of infusions. PMID- 1410979 TI - [Potential use of the sauna in the long-term treatment of hypertensive cardiovascular circulation disorders--a comparison with kinesiotherapy]. AB - The authors report about the long-term response (one and three years) of blood pressure and heart frequency under rest and load (50 W) in patients with hypertension, coronary heart disease, essential hypertension and after aortocoronary venous-bypass operation (ACVB) (n = 65) under regular visits (twice a week) to the Finnish sauna. In comparison, 68 hypertensive patients who took a regular kinesiotherapy (running and swimming) were studied. Besides the parameters of heart circulation mentioned above, peripheric microcirculation (M. tibialis anterior) by means of xenon-133 muscle clearance and central hemodynamics by means of LVEF (single probe with In 113) were studied in CHD patients. Cardiac output at rest and under 50 W load was recorded in hypertensive patients. It was shown that regular balneotherapy had a positive effect on regulation of blood pressure and hemodynamics in patients with hypertension or CHD with hypertension, as had kinesiotherapy in hypertensive patients. PMID- 1410980 TI - [Main involvement of the central nervous system in alcoholism]. AB - The effects of alcohol on the central nervous system can be subdivided into three main categories: the effects of acute intoxication (drunkenness, acute encephalopathy, stroke), the effects of tolerance and ethanol withdrawal (delirium tremens, seizures) and the delayed manifestations of chronic alcohol consumption (cerebellar degeneration, Wernicke's encephalopathy, dementia). PMID- 1410981 TI - [Livedo racemosa, skin necrosis at the basal toe joint]. AB - An 81 year old male patient treated by sulfonylurea and diet was known to have type II diabetes for three years. Because of pulmonary embolism phenprocoumon had been administered for four months. Painful livedo racemosa developed acutely on both lateral sides of the feet and the left knee. A necrosis of the skin over the base of the left small toe developed within a few days. On the basis of the clinical picture cholesterol-embolism was diagnosed. Since anticoagulation is known to promote cholesterol-embolism it was discontinued. Prostaglandin E1 infusions into both legs were administered. Within 3 months the cutaneous lesions healed completely. PMID- 1410982 TI - [What is your diagnosis? osteochondroplastic tracheo-bronchopathy]. PMID- 1410983 TI - [Interleukins]. AB - Interleukins are polypeptide hormones which are primarily but not exclusively synthesized by cells of the immune system (monocytes/macrophages, T- and B lymphocytes). Up to now 12 interleukins (IL-1 to IL-12) have been described. The central function of the interleukins is the orchestration of the different cells of the immune system during host defence against pathogens. Besides the regulated stimulation of the immune reaction against foreign antigens, interleukins are involved in the stimulation of unspecific inflammatory reactions and in the induction of the acute phase response. PMID- 1410984 TI - [Magnetic resonance imaging in spinal cord diseases: 127 cases]. AB - Acute or chronic spinal cord syndromes with or without evidence of cord compression are a common diagnostic problem in neurology. Magnetic resonance imaging (MRI) was performed on 127 patients to assess the sensitivity of this examination in detecting local spinal cord lesions. The most common location noticed in this study were the cervico-thoracic (40.9%) and cervical regions (33.8%). A total spine examination accounted for 14.9% of the examinations performed, and the lumbar spine was evaluated in 10.2%. An increased signal corresponding to plaques of multiple sclerosis was the most frequent diagnosis (25 cases), followed by cervical narrowing of the spinal canal and cervical disk diseases (23 cases), neoplasms (15 cases), spinal cord infarctions (12 cases), spinal infections (6 cases) and spinal cord injuries (3 cases). A myelopathy of undetermined etiology was diagnosed in 19 cases. MRI is very sensitive in multiple sclerosis, but it is not possible to diagnose the disease from abnormal scan only, other supportive laboratory results, such as oligoclonal bands, are necessary. MRI is very useful in evaluating intraspinal cord parenchymal lesions, such as neoplasms or congenital abnormalities. PMID- 1410985 TI - [Rhabdomyolysis in body building. Report of a case and literature review]. AB - A 24-year-old man was sent to the emergency unit and evaluated with the symptom of acute right-sided chest pain. Myocardial infarction and pulmonary embolism were excluded. A creatine kinase (CK) serum concentration of 17,034 U/l (normally up to 270) was found. The patient gave a history of excessive body-building exercises on the previous day. During the follow-up period symptoms resolved within several days, and CK values gradually diminished. A review of current literature on rhabdomyolysis in patients with body-building is presented. PMID- 1410986 TI - [A case from practice (250). Costochondritis]. PMID- 1410987 TI - [What is your roentgen diagnosis? Pulmonary edema with enlarged hili]. PMID- 1410988 TI - [Cerebral complications and general anesthesia]. AB - Postoperative cerebral dysfunction is usually assumed to be a consequence of anaesthesia. Temporary postoperative confusion is quite common. This review points out that the anaesthetic technique is clinically relevant for mental dysfunction only in the few hours immediately following operation. Of primary importance are the preoperative state of the patient, the drugs used in the perioperative period, the type and duration of the operation, the technique of postoperative analgesia and sedation and the postoperative clinical course of the patient. Cerebral infarction is a very severe but rather rare complication which occurs mainly after the operation. The incidence of perioperative cerebral infarction is about 1% in 65-year-old patients and increases with higher age. An asymptomatic preoperative carotid bruit is not a risk factor; therefore, invasive investigations are not warranted. The most frequent cause for cerebral insults are emboli. Intraoperative hypotensive periods are very rarely responsible for cerebral insults. Peripheral and central nervous lesions due to positioning of the patient for the operation occur not frequently and are certainly an avoidable neurologic complication. Hypoxic cerebral damages are usually the consequence of anaesthetic mismanagement. Today they are very rare, due to modern monitoring techniques. PMID- 1410989 TI - [Cerebrovascular accidents and surgery]. AB - There are very few observations on the occurrence of stroke after general surgery; the incidence lies between 0.2 and 0.7%. On the other hand, cerebrovascular accidents are mainly seen after cardiac and carotid surgery, where the incidence is high (5%). Strokes are also an important cause of morbidity and mortality following orthotopic transplantations, particularly heart, heart/lung and liver transplantations. PMID- 1410990 TI - [Spinal lesions in surgery of the aorta]. AB - Aortic diseases in particular aneurysms may be accompanied by spinal ischemia occurring either spontaneously or as complications of surgical interventions. Surgery of the abdominal or thoraco-abdominal aorta is followed in 5 to 15% by ischemia of the spinal cord, in exclusively abdominal interventions in 1.5%. Clinical manifestation depends largely on anatomy of the spinal vessels. If complete transverse myelopathy does not occur, presentation as anterior or posterior arterial ischemic syndrome is common. Other forms of myelopathy are rare. Perfusion deficits through intercostal and lumbar arteries are important in pathogenesis. The great radicular artery is particularly important. Ischemia occurs after hypotensive episodes (ruptured aneurysm) intraoperative clamping of the suprarenal aorta or by occlusion (thrombotic, arterio-arterial embolism). Careful surgical techniques are important for prevention of these neurologic complications. Possibilities for treatment and chances for spontaneous recovery of established spinal-cord lesions are poor. PMID- 1410991 TI - [Ilio-inguinal and genito-femoral neuralgia. Causes, clinical aspects, therapy]. AB - Entrapment neuropathy of the ilioinguinal and of the genito-femoral nerves is a rare but sometimes very painful complication of abdominal surgery (herniorrhaphy, appendectomy, nephrectomy, gynecological surgery, removal of bone from the inner table of the iliac crest, etc.). Sometimes symptoms develop during a normal pregnancy or delivery. Spontaneous entrapment of the ilioinguinal nerve as it passes through the Mm. obliquus internus and transversus abdominis has also been observed. We have operated such a case. The causes, features and the associated findings of entrapment neuropathy of the two nerves are pointed out. In the frequent cases attributable to previous surgery the retroperitoneal resection of the nerves is advocated instead of a local revision, which is usually unsuccessful due to the impossibility of finding and restoring the fine nerves in a dense scar. PMID- 1410992 TI - [A case from practice (251). 1. HIV-infection CDC IVE--chronic lymphocytic interstitial pneumonia. 2. Chronic emphysematous bronchitis in severe nicotine abuse. 3. Status following hepatitis B, syphilis and stomach ulcer 1981 and 1982. 4. Status following bilateral femoral fractures 1958]. PMID- 1410993 TI - [A case from practice (252). Hyperkinetic heart syndrome]. PMID- 1410994 TI - [What is your roentgen diagnosis? Ulcerating leiomyosarcoma of the small intestine]. PMID- 1410995 TI - [The treatment of cardiac insufficiency past and present]. PMID- 1410996 TI - [Heart sounds--a mathematical transformation of blood pressure? On the origin of heart sounds]. AB - Two main theories exist concerning the origin of the heart sounds. The first proposes that rapid pressure fluctuations cause the cardiac valve leaflets to vibrate and produce the sound. The second theory suggests that sudden pressure perturbations cause the entire cardiohemic mass to vibrate as a whole. In 35 patients (26 men and 9 women, aged 18 to 73) with various heart diseases microtransducer catheters (Millar) were used to simultaneously record aortic pressures and aortic internal phonocardiograms in order to determine if they had a common mode of origin and propagation. The propagation velocities of the first heart sound and the foot of the aortic pressure pulse were found to be similar, 5.24 +/- 0.61 m/s and 5.97 +/- 1.87 m/s respectively (+/- SE). It was possible to derive facsimiles of the aortic internal phonocardiogram by double differentiation of the corresponding aortic pressure pulse and conversely to derive the pressure pulse by double integration of the phonocardiogram. These data support the concept that the low-frequency pressure variations produced by the entire cardiohemic mass, which predominate in the aortic pressure pulse waveforms, are generated and propagated in the same manner as the high-frequency pressure variations, which are the first and second heart sounds. PMID- 1410997 TI - [Elevation of the ST-segment in the electrocardiogram and ischemic injury current]. AB - The TQ segment depression and the ST segment elevation in the electrocardiogram during acute myocardial ischemia are caused by flow of injury current. This current flows between potential gradients across the ischemic border. The initial change is the TQ segment depression, which is brought about by a positive shift of the resting membrane potential of the ischemic cells. After 1 to 2 minutes ST segment elevation develops as a consequence of the action potential shortening and loss of plateau. The loss of potassium ions and ensuing extracellular K+ accumulation is the major cause of the alterations in action potential. After 15 to 20 minutes of ischemia, electrical cell-to-cell uncoupling occurs and interrupts the flow of injury current (decrease of TQ segment depression and ST segment elevation), producing conduction block. PMID- 1410998 TI - [Coronary thrombosis--an old concept in a new light]. AB - The morphologic-clinical links in acute myocardial ischemia have been established in the last few years. Angiographic and biochemical investigations have contributed to the understanding of the connection between the acute coronary lesion (fissure or rupture of a plaque, dissection) and the dynamic process of thrombus formation, lysis and coronary spasm that occur during the first minutes and hours of acute myocardial ischemia. Deep arterial lesions with thrombotic tendency also occur after coronary bypass operations, thrombolysis and PTCA. Conventional antithrombotic substances like aspirin and heparin are only partially effective, and new compounds are tested which either inhibit platelet aggregation or thrombin formation more completely. Hopefully, these new drugs will prevent reocclusion after thrombolysis and restenosis after PTCA more effectively. PMID- 1410999 TI - [Myocardial infarct without classical Q-waves in the ECG]. AB - In this article the ECG pattern of myocardial infarction not associated with the commonly seen pathologic Q waves (greater than 0.03 s) or QS waves is discussed. In a short introduction the differential diagnosis of pathologic Q or QS waves is recalled. Thereafter, the authors insist on their experience, that the diagnosis of infarction should generally be based on the combination of RIsk factors, THOracic pain, a pathologic ECg and elevated cardiac ENzymes. Therefore, the diagnosis of a myocardial infarction should be made only, if it is 'RITHOCGENE' (abbreviation of the above-mentioned combination). The typical or possible 'non-Q wave infarction' ECG patterns are listed, including a normal ECG. PMID- 1411000 TI - [Non-invasive assessment of left ventricular diastolic function disorder using Doppler echocardiography]. AB - Symptoms of a variety of cardiac diseases may well be caused predominantly by diastolic dysfunction, which appears to be one of the first detectable cardiac alterations. Diastole represents a complex interplay of multiple factors. Doppler echocardiography offers a noninvasive and relative simple method to assess left ventricular volumetric filling rates. The pulsed-wave Doppler method enables us to measure mitral flow velocities. Two distinct mitral flow velocity patterns have been recognized for situations with diastolic dysfunction. The pattern of delayed relaxation was reported in primary and in secondary left ventricular hypertrophy, myocardial ischemia and infarction and in dilated cardiomyopathy. The pattern of increased stiffness was described in constrictive pericarditis, restrictive processes and in heart transplant rejection. Doppler echocardiography has shown to be a helpful diagnostic tool, but a number of factors influencing mitral flow measurements have to be considered in each case, as there are age, heart rate, loading conditions and mitral regurgitation. Further studies are needed with respect to future control of therapeutic interventions and prognostic statements. PMID- 1411001 TI - [Complementary information from Doppler echocardiography in the electrocardiogram in the basic assessment of chronic coronary heart disease, especially following a myocardial infarct. Observations from an ambulatory cardiology clinic]. AB - In chronic ischemic heart disease, Doppler echocardiography (DE) at rest permits semiquantitative evaluation of scarring and remodelling processes, global ventricular function and, frequently, regional wall motion state. Late complications are detected, namely infarct expansion, true and false ventricular aneurysm, mitral insufficiency, thrombus formation, and associated valvular and aortic diseases are discovered. We studied 100 patients with known chronic coronary artery disease referred for noninvasive evaluation, including electrocardiogram (ECG) and DE. In all patients, the global left-ventricular function was satisfactorily assessable. In roughly two thirds of the documented infarctions. DE confirmed the ECG diagnosis and permitted a more precise diagnosis in the majority of them in terms of localization and/or dimension of the necrosis. In one third of the patients. DE clarified inconclusive ECG tracings. Thus, the baseline noninvasive investigation with ECG and DE is a potent tool in the management of chronic ischemic heart disease, serving as a guide to further investigation and to treatment adjustments. PMID- 1411002 TI - [The elderly patient in cardiology]. AB - This paper summarizes the special aspects of cardiovascular disease in the elderly. Arterial hypertension, heart failure and electrical disturbances may often lead to a different therapeutic approach in this clinical setting. Myocardial infarction is often complicated and may lead to considerable disability; therefore, thrombolytic therapy should be considered also in elderly patients. Coronary angioplasty and heart surgery are successfully performed in patients greater than or equal to 80 years of age, but special consideration has to be given to the functional states and the presence of concomitant disease in these patients. PMID- 1411003 TI - [What is your diagnosis? Myelitis of the cervical spine]. PMID- 1411004 TI - [Urinary tract infection in women in daily clinical practice]. AB - Questions concerning the clinical picture, diagnosis and treatment of uncomplicated urinary tract infections in women related to daily practice are discussed on the basis of personal experience and a review of the literature. Indications and rationale for a single-dose therapy with Cotrimoxazole, Trimethoprim or Fosfomycin are detailed. Special considerations are given to therapeutical approaches to recurrent infection as well as special situations like asymptomatic bacteriuria, acute urethral syndrome, bacteriuria in pregnancy and nosocomial, catheter-associated infections are discussed. PMID- 1411005 TI - [The value of CT and MRI in the assessment of basal encephaloceles in children]. AB - Basal cephaloceles of the child are rare pathologies which require accurate preoperative imaging work-up. The CT and MR studies of six children with surgically proven basal cephalocele were retrospectively reviewed to evaluate the role of CT and MR in the preoperative work-up of a basal cephalocele of the child. In five patients, MR allowed to define the nature and topography of the cephalocele, and allowed an accurate depiction of the optic tract, ante- and post hypophysis and associated agenesis of corpus callosum when present. 3-D CT allowed in one case a more precise depiction of the basal bony defect. MRI allows in a non invasive and non ionising way the best depiction of herniating meninges, brain or ventricles as well as associated cerebral anomalies. PMID- 1411006 TI - [A case from practice (253). 1. Ross syndrome. 2. Residual, probably post infectious lymphadenopathy]. PMID- 1411008 TI - [New diagnostic windows to heart and blood vessels]. PMID- 1411007 TI - [What is your diagnosis? Styloid syndrome. Discrete right convex abnormality of the apex at C6. No inflammatory changes]. PMID- 1411009 TI - [Assessment of blood flow in hart and large vessels using Doppler color flow mapping]. AB - Two-dimensional echocardiography allows the noninvasive assessment of the morphology and the movement of cardiac structures, including valves and ventricular walls. Color Doppler flow imaging presents a spatial visualization of blood flow, superimposed on two-dimensional echocardiographic images. The color indicates the direction of flow. Turbulent flow is readily identified by the 'mosaic pattern' of the color flow signal. The method facilitates the detection and localization of obstruction to flow, valvular regurgitation or a shunt. PMID- 1411010 TI - [Transesophageal echocardiography: technique, indications and findings]. AB - The introduction of transesophageal echocardiography (TEE) as a 'semi-invasive' technique with few complications in clinical practice represents a major diagnostic advance in the evaluation of cardiac disease. The close anatomic vicinity of the transducer to the heart and thoracic aorta allows the use of high frequency devices with better resolution compared to transthoracic echocardiography. Furthermore, the diagnostic gain when evaluating structures that are poorly visualized by the transthoracic approach such as the left atrial appendage, interatrial septum, prosthetic valves and the thoracic aorta is highly improved by TEE. Major indications for TEE include the search for a cardiac source of embolism and cardiac tumors, the work-up prior to balloon mitral valvuloplasty, the evaluation of prosthetic valves and the search for vegetations and aortic dissection. After a short summary of patient preparation, instrumentation and examination technique, the major indications, contraindications and complications are reviewed on the basis of our own experience and the literature. PMID- 1411011 TI - [What is your diagnosis? Gout (not excluding bacterial superinfection)]. PMID- 1411012 TI - [Percutaneous endoscopic gastrostomy (PEG) for long-term nutrition--comparison of 2 different caliber tubes]. AB - Percutaneous endoscopic gastrostomy (PEG) is often used nowadays for long-term enteral nutrition in patients with swallowing disorders and severely altered esophageal-duodenal transit. The most common indications for gastrostomy tubes were neurological disturbances and malignancies of the oropharynx and esophagus. We compared in a prospective sequential trial PEG-tubes of two different sizes (2.9 mm [CH-9] vs. 4.8 mm [CH-15]) with respect to placement, complications, durability and handling. The tube was successfully placed in 51 of 52 patients (98%). In 1 patient placement was impossible due to missing diaphanoscopy. The mean observation period was 22 weeks for the CH-9-tubes (n = 28) and 14 weeks for the CH-15-tubes (n = 23). The only early complication was 1 case with a hemorrhage at the site of implantation (CH-15). In both groups 2 cases of local infection were noted. In the CH-9-group 2 PEG-tubes disappeared into the stomach and in 1 case a cicatricial granuloma developed. In the CH-15-group a leak occurred 10 days after implantation. All complications were treated conservatively. There was no causal relationship between the size of tube and the complications. The period of implantation was mostly limited by the death due to the underlying disease of the patient and was not related to the type of PEG tube. We conclude the both PEG-tubes were easy to place, safe and effective means of providing enteral nutrition. We would, however, recommend CH-15-tubes for long term nutrition, since in our experience they were less frequently obstructed and handling for the nurses was easier. PMID- 1411013 TI - [How reliable is oscillometric blood pressure determination at the finger using the Omron device?]. AB - The precision of oscillometric blood-pressure measurements on the finger with the model HEM-812F, manufactured by Omron, was compared to the standard method. The digital measurements from 180 inpatients (115.0 +/- 1.2 mmHg systolic, 68.8 +/- 0.8 mmHg diastolic) were significantly lower than oscillometric measurements from the upper arm using a Bosomat (121.3 +/- 1.4 mmHg systolic, 74.2 +/- 0.9 mmHg diastolic). Correlation coefficients were r = 0.713 for systolic and r = 0.683 for diastolic values, with significant variance of individual values. In direct comparison of the two methods immediately after ergometry the differences were even greater (57 mmHg systolic, 32 mmHg diastolic). Significantly lower digital pressures at the finger were noted in comparison with direct blood-pressure measurements after punction of the femoral artery. Because of significant differences of blood-pressure measurements compared to the Riva-Rocci method, the digital measurement with the HEM-812F device (Omron) can not be generally recommended. PMID- 1411015 TI - [A case from practice (254). Adult-type cystic kidney. HIV infection group CDC IV C2]. PMID- 1411014 TI - [Intestinal leiomyoma. Case report and discussion of the difficult assessment of grade]. AB - The case of a male patient operated for a leiomyoma of the jejunum is presented. The clinical symptoms, the morphological differential diagnosis and the problems evaluating aggressiveness of this tumour are discussed. We intend to demonstrate that histopathological diagnostic implicate a certain grade of uncertainty too. With the example of leiomyoma we like to show that diagnosis means a tight cooperation of the clinician and his pathologist by collecting clinical and histomorphological data. PMID- 1411016 TI - [Magnetic resonance imaging: cardiological diagnosis]. AB - Cardiovascular magnetic resonance imaging (MRI) has been in clinical use for barely a decade. During this relatively short period MRI has established itself as an important diagnostic instrument. MRI is an intrinsically three-dimensional, completely noninvasive technique. Its inherent high contrast between the flowing blood on the surrounding tissue make MRI an ideal diagnostic method for cardiovascular diseases, since it does not expose patients and staff to ionizing radiation and there is no need for the application of contrast media. The high spatial and excellent contrast resolution are the basis for the distinct delineation of the cardiovascular pathoanatomy. Infarcted and non-infarcted myocardium may be differentiated by the assessment of tissue relaxation times. With the use of Cine MRI, global and regional ventricular function may be quantified and bloodflow within cardiac chambers may be analyzed. Today's indications for cardiovascular MRI based on personal experience and the literature are presented. PMID- 1411017 TI - [Digital subtraction angiography for the assessment of myocardial perfusion]. AB - Coronary angiography does not only permit to evaluate the severity of coronary disease but also to assess coronary flow reserve in various myocardial perfusion areas by digital processing. Use of colour flow mapping allows the assessment of both, density as well as distribution velocity of contrast-medium (= parametric imaging). The advantage of this technique is given by the possibility to assess coronary flow reserve not only at rest but also under physiologic situations such as bicycle ergometry. Clinical investigations have shown that coronary flow reserve determined after papaverine administration does not correlate with physiologic conditions such as physical exercise. PMID- 1411018 TI - [Positron emission tomography in cardiological diagnosis: principles and clinical application]. AB - Positron emission tomography (PET) is an emerging new cardiac imaging modality which allows sophisticated tissue characterization using radiopharmaceuticals. This technique provides absolute quantification of regional tracer concentration using short-lived isotopes such as carbon-11, oxygen-15 and nitrogen-13, which can be easily incorporated in many compounds without changing their biological behaviour. These technical advantages are somewhat offset by the high cost of this technology which includes camera as well as on site cyclotron required for the preparation of radiopharmaceuticals. Recent clinical dates suggest that unique information can be obtained with PET. Using blood flow tracers in combination with PET, coronary artery disease can be detected and localized with high diagnostic accuracy. First studies comparing Tl-201 SPECT and PET in the same patient population indicate diagnostic superiority of PET. In combination with tracer kinetic models, regional myocardial blood flow can be quantitated and the functional significance of coronary artery stenosis defined by regional coronary reserve measurements. The assessment of regional glucose metabolism by PET with the tracer F-18 deoxyglucose has received wide clinical acceptance. Metabolic imaging in patients with advanced coronary artery disease allows the delineation of ischemically compromised but viable myocardium. Selection of patients for revascularization based on this scintigraphy tissue characterization has been shown to have a high predictive value for subsequent tissue recovery. Comparison of PET/FDG imaging with thallium-201 scintigraphy for assessment of tissue viability indicate that, in patients with fixed thallium-201 defects, additional diagnostic information can be obtained by this more expensive technology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411019 TI - [A case from practice (255). Munchausen syndrome in borderline personality. Bacterial right and left heart endocarditis following i.v. injection of feces. Abscessed pneumonia. Acute post-infection glomerulonephritis with reversible kidney failure. Multi-drug addiction with i.v. drug abuse (Temgesic and other opiates)]. PMID- 1411020 TI - [Idiopathic scoliosis: screening, diagnosis and treatment]. PMID- 1411021 TI - [The child's foot in daily practice]. PMID- 1411022 TI - [Total knee prosthesis with preservation of the posterior cruciate ligament: the Lausanne experience]. PMID- 1411023 TI - [Importance of meniscal and ligamentous lesions in the long-term prognosis of fractures of the tibial plateau]. PMID- 1411024 TI - [Surgery of the rotator cuff--indications and results]. PMID- 1411026 TI - [Painful muscles syndrome: the unknown once again]. PMID- 1411025 TI - [Rapidly destructive coxarthrosis]. PMID- 1411027 TI - [Osteoarticular manifestations of brucellosis. Apropos of 2 cases of brucellosis induced sacroiliitis]. PMID- 1411028 TI - [Panic disorders: current findings and clinical approach in pharmacological treatment]. PMID- 1411029 TI - Percutaneous renal stone removal using the Swiss Lithoclast. PMID- 1411030 TI - Management of ureteric calculi (minimally invasive therapy of ureteric stones). AB - As documented with results obtained in 1685 patients the treatment of ureteric stones is today based on ESWL in situ and ureteroscopy with semirigid, ultrathin ureteroscopes and laser lithotripsy. All stones in the upper third of the ureter and larger stones in the distal third of the ureter are preferably treated with ESWL in situ whereas smaller stones in the distal ureter are better treated endoscopically. Midureteric stones remain the domain of primary ureteroscopy; with moderate obstruction in the asymptomatic patient it may also be acceptable to wait for the stone to pass into the distal ureter spontaneously to be treated by ESWL in situ there. Manipulating stones back into the kidney and treating them by ESWL there (pushback/ESWL) offers no advantage over ESWL in situ, as the results are similar, yet morbidity is higher. Blind instrumentation and open surgery have lost all justification. PMID- 1411031 TI - [The treatment of urinary calculi in 1992]. PMID- 1411032 TI - Long term follow-up after ESWL of large kidney stones. AB - In 76 patients (53 women and 23 men) aged 24-92 years, extracorporeal shock wave lithotripsy (ESWL) was performed between June 1986 and December 1988 as monotherapy for large kidney stones (diameter > 2.5 cm). There were 41 complete and 24 partial staghorn calculi. The patients were treated with the Dornier HM3 lithotripter under sedoanalgesia. Of the 60 patients with large stones whose last ESWL treatment was at least 24 months earlier, only 15 ultimately came for this long-term control check-up. Reports on 15 other patients were received from their doctors stating that the patients were doing well, not having new stone episodes. These subjects had to be excluded from final evaluation since they did not fulfill all requirements. Thirty patients had either moved out of the area or were from distant locations and therefore unable to appear. Creatinine was normal and urinalyses negative in these 15 patients; 12/15 were stone-free. The ones who were not had small remnants in the lower pole calices which did no harm at all. One patient already had elevated pretreatment blood pressure; 6/14 with normal blood pressure before ESWL showed elevated values 30 or more months after hte last ESWL. Radio-isotope examinations with separate clearance tests demonstrated no real evidence of loss of kidney function on the treated in comparison with the untreated side. Sonographic findings on the longitudinal and transverse diameter of the treated and untreated kidneys with regard to total number of shock waves did not show marked differences as they all remained below the 9% limit. PMID- 1411033 TI - [Laser lithotripsy of ureteral stones using a pulsed dye laser with automatic tissue recognition]. PMID- 1411034 TI - The "TUR-Catheter", a new catheter for postoperative drainage of the bladder. AB - A new catheter for postoperative irrigation of the bladder after operation of the prostate or bladder is introduced. Instead of 1 to 3 large holes measuring 5.5 6.5 mm by 2.5-3 mm at its tip, as in common catheters, it has 32 drainage holes, each of them measuring 1.5 mm in diameter. This type of construction still secures sufficient unhindered drainage of the bladder, even if the majority of holes is obstructed. Thus, postoperative tamponade is prevented. PMID- 1411035 TI - Diagnostics and treatment of prostatitis: an actualized overview. PMID- 1411036 TI - [Prostatic cancer before the age of 50. Diagnostic and therapeutic considerations]. PMID- 1411037 TI - Functional restoration & reconstruction of the incontinent female urethra. PMID- 1411038 TI - Pelvic endometriosis. Some pathophysiological and clinical conditions. PMID- 1411039 TI - [Are peritoneal implants of endometriosis painful?]. PMID- 1411040 TI - [Role of IVF/ET in the treatment of endometriosis]. PMID- 1411041 TI - [Reconstruction of the breast using a transverse abdominal muscle flap]. PMID- 1411042 TI - [Traumatic pathology of the scapulo-thoracic girdle]. PMID- 1411043 TI - [The Roux esophago-jejuno-gastrostomosis (1906)]. PMID- 1411044 TI - [Cytokines-endothelium interaction: its role in the thrombotic process]. AB - The in vivo relationship between the immune and the coagulation systems is a well documented fact. In a number of pathological conditions, thrombosis is not understood isolately, but in the context of inflammation and immunity. The mediators in these complex multidirectional interactions are the cytokines, a group of soluble peptides which act on surface cellular receptors, with immunoregulatory properties. These molecules influence negatively the physiological antithrombogenic situation by two different mechanisms. They are involved in processes which disrupt the endothelial integrity, and at the same time, they are capable of activating the endothelium in a prothrombotic manner, by stimulating procoagulant activities and by inhibiting different anticoagulants. PMID- 1411046 TI - [Brain death?]. PMID- 1411045 TI - [Nutrition of the terminally ill patient: dietetic guidelines]. AB - Food is a factor of great importance in personal relationship during the terminal phase. There are numerous causes of appetite and taste disturbances that must be known by the family and physician. Some ideas are provided about the different ways to improve nutrition and appetite as a part of a plurisymptomatic management to maintain the patient's comfort until his last days of life. PMID- 1411047 TI - [The university and their professors]. PMID- 1411048 TI - [Surgical treatment of the tumors of the hand and the wrist]. PMID- 1411049 TI - [Single lung transplantation]. AB - Thirteen single lung transplantations have been performed in our department for non-infected end-stage lung diseases. Two patients died after surgery; a female patient died of uterine carcinoma one year and six months after the operation. The remaining ten patients are alive; they have resumed an active life and often working. The number of single lung transplantation is rapidly growing in the world, whereas heart-lung transplantation is regressing considerably. PMID- 1411050 TI - [Health effects of chronic exposure to tobacco smoke on a non-smoker population]. AB - A study devised to evaluate the effects of chronic exposure to tobacco smoke on the health of a population of non-smokers was conducted in a prison. Fourteen volunteers among male, non-smoking prisoners in good health and without history of lung disease were put for thirty days in a cell that was already occupied by three smokers. These subjects were examined on arrival and on the 30th day of their imprisonment. The examination included filling a questionnaire concerning daily habits and food, respiratory function tests, measurement of CO in the expired air, measurement of nicotine, cotinine, thiocyanates and cadmium concentrations in blood and in urine, and measurement of mutagenic substances excreted. The purpose of the study was to detect possible changes in the variables tested between the first and last days of confinement. No significant difference could be demonstrated within this lapse of time. These results are in agreement with the data available in the literature. In the present state of our knowledge, it is difficult to find evidence of a biological impact, notably on the concentrations of the specific indicators nicotine and cotinine, in subjects passively exposed to tobacco smoke. PMID- 1411051 TI - [Bilateral chylothorax after mild trauma: apropos of a case]. AB - The authors report a new case of bilateral chylothorax predominant on the left side, which occurred after movements of body trunk hyperextension in a 52-year old woman without any notable history. The clinical signs revealing the lesion were left thoracic pain and dyspnoea. The effusion had been preceded by a painless and transient left cervical tumefaction. The outcome was favourable after two left pleural draining punctures and rest. PMID- 1411052 TI - [Giant cell tumors of the ribs. Apropos of a case]. AB - The authors report a case of grade I-II giant-cell tumour of the ribs extending to the thorax and the vertebral column. The tumour was treated by surgical resection followed by vertebral curettage in two stages and adjuvant regional radiotherapy. Giant-cell tumours of the ribs are exceptional and rarely found in the literature. They raise a therapeutic problem (surgery is essential, but radiotherapy is controverted), and a prognostic problem (there is always a potential risk of recurrent malignancy). PMID- 1411053 TI - [Apropos of "cardiac pseudo-asthma"]. PMID- 1411054 TI - [Selective digestive decontamination in intensive care patients. European Society of Intensive Care Medicine. Consensus Conference]. PMID- 1411055 TI - The advancement of dental laboratory technology into professional status. PMID- 1411056 TI - Management and leadership--is your laboratory on automatic pilot? AB - Many management professionals have attempted to define the relationship between leadership and management. Some believe that leadership and management are interrelated characteristics, with one perhaps an extension of the other; others maintain that they are different qualities altogether. Few would argue with the notion, though, that leadership is a great quality for managers to have. This article explores management and leadership, and looks at some ways to enhance and encourage leadership in your laboratory. PMID- 1411057 TI - Basics for selecting attachments. PMID- 1411058 TI - P.C. Wafer: an improvement in the fixed removable implant system. PMID- 1411059 TI - Preparing for the 90s--increasing production while decreasing costs. PMID- 1411060 TI - The Consumer Price Index (CPI). PMID- 1411061 TI - Compatibility in porcelain to metal systems: Part 3. AB - As described in parts one and two of this article, all the steps leading to the finished casting can influence the compatibility between porcelain and alloy. This final part of the article will examine the influences of metal conditioning and thermal handling on the completed restoration. PMID- 1411062 TI - Changes are needed. PMID- 1411063 TI - Certification and manpower. PMID- 1411064 TI - New focus on sexual harassment: a review of workplace policies. PMID- 1411065 TI - Controlling porosity in microwave processed acrylic. AB - The purpose of this study is to investigate the relationship of bench curing techniques, processing time and microwave wattage to porosity in the processed acrylic resin. PMID- 1411067 TI - CDT today: candidate rights to appeal grades. PMID- 1411066 TI - Permanent soft reline of a Swing Lock partial. PMID- 1411068 TI - Processed bases for complete dentures. PMID- 1411069 TI - Organizational climate, motivation and productivity. PMID- 1411070 TI - CDT today: the successful grade appeal. PMID- 1411071 TI - The preliminary prosthetic consultation form. PMID- 1411072 TI - New generation of palladium-indium-silver dental cast alloys: a review. PMID- 1411073 TI - The employer's role in reporting workers' compensation claims. PMID- 1411074 TI - Engineering and physics in dental technology. 1. AB - This work is a compilation of the principles of engineering and physics that are involved in the design and construction of various types of prostheses in the dental laboratory. It is intended as a reference of scientific doctrines for dental technicians who wish to advance their knowledge and skills. This article is the first of several that will be published in Trends & Techniques during the next several issues. The article in its entirety is by no means complete--the field is too enormous to identify all the tenets that apply, and future scientific advancement will certainly add others. Some elements of biomechanics are included in this work because of the interrelationship of biomechanics to engineering. PMID- 1411075 TI - Treatment of the partially edentulous patient. PMID- 1411076 TI - Fabrication of a custom-fitted mouthguard. PMID- 1411077 TI - Individual responsibility--involving and empowering your people. PMID- 1411078 TI - The set-up and process of a mandibular hybrid denture. PMID- 1411079 TI - Engineering and physics in dental technology. Part 2. AB - Part 2 covers the areas of friction and lubricants, cross sections, parallelism, passivity and equilibration, levers, reducing the radius, immobilization, and transmitral of forces. Some elements of biomechanics are included in the article because of the interrelationship of biomechanics to engineering. PMID- 1411080 TI - The use of lateral rotated papillae flaps as an alternative source for reconstructing gingiva. PMID- 1411081 TI - The clinical effects of electrostimulation on salivary function of Sjogren's syndrome patients. A placebo controlled study. AB - A multi-center double-blind study of an electro-stimulator device was conducted to evaluate its ability to increase the production of saliva and reduce clinical symptomatology. A total of 77 Sjogren's syndrome patients at three centers were assigned to active devices (n = 40) or to placebo devices (n = 37). There were 2 male and 32 female patients assigned to active devices, and 1 male and 36 female patients assigned to placebo devices. The age range with the greatest number of patients was 60-69 years making up more than 31% of the study population. The selection criteria required the patients to have no greater than 0.2 g/min of whole salivary production (approximately 19% of normal salivary production). At the start of the study, the patients assigned the active device had a mean salivary production of 0.06 ml per min (6% of normal) and patients assigned placebo devices had a mean salivary production of 0.07 ml per min (7% of normal). There were three scheduled visits, 2 weeks apart, over a treatment period of 4 weeks. At all visits, the patients using active devices showed a statistically greater (P = 0.005 to 0.02) increase in the production of saliva than placebo patients. The study also evaluated the reduction of patients symptoms associated with xerostomia. Patients showed significant improvement in (1) difficulty in swallowing and (2) burning tongue (P = 0.008). Some patients on their initial visit had no response to the active device and did not show a significant response at subsequent visits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411082 TI - Influence of prolonged neuropsychological testing on immunoregulatory cells and hormonal parameters in patients with systemic lupus erythematosus. AB - The influence of a 2-h neuropsychological stress test on plasma catecholamines, cortisol, and on the distribution of lymphocyte subpopulations was studied in 14 patients with systemic lupus erythematosus (SLE), 10 patients on prednisone treatment (without collagenosis), and 14 sex-and-age-matched healthy controls. Psychological stress induced comparably significant increases in plasma adrenaline and noradrenaline levels as compared with baseline values (P less than 0.05) in all three groups, whereas plasma cortisol remained unchanged. The rise in plasma catecholamines was accompanied by a significant cell mobilization in healthy subjects and prednisone-treated patients, but not in patients with SLE. CD19+ cells increased significantly in number from baseline in healthy subjects and prednisone-treated controls (P less than 0.05), while remaining unchanged in SLE patients. In conclusion, SLE patients showed a reduced cell mobilization due to psychological stress despite hormonal alterations paralleling those of healthy subjects or prednisone-treated patients without collagenosis. PMID- 1411083 TI - Spontaneous expression of immediately-early response genes c-fos and egr-1 in collagenase-producing rheumatoid synovial fibroblasts. AB - In view of the important role of interstitial collagenase in the pathogenesis of rheumatoid arthritis (RA), we studied the expression of fibroblast-type collagenase in rheumatoid synovium and searched for its potential transcription factors, namely the oncoprotein c-fos and the early-growth-response gene-1 (egr 1), an inducible zinc-finger encoding gene. Elevated levels of RNA sequences complimentary to c-fos and egr-1 cDNA probes could be detected in cytoplasmic extracts of collagenase-expressing synovial fibroblast-like cells when compared to equivalent RNA amounts isolated from control fibroblasts. Utilizing immunocytochemistry, immunoreactivity for c-fos oncoprotein was found in 13 of 19 joint specimens obtained from patients with active RA. These oncoprotein data were positively correlated to the collagenase expression in the same specimens. Moreover, immunohistochemical analysis confirmed the localization of both oncoprotein c-fos and fibroblast-type collagenase within synovial fibroblast-like cells attached to bone erosions. PMID- 1411084 TI - Rheumatic manifestations of infective endocarditis. AB - Rheumatic manifestations are common and varied in infective endocarditis. We performed a retrospective case analysis on 87 patients with 93 episodes of infective endocarditis admitted to Flinders Medical Centre over an 11 year period (1980-1990). Disabling musculoskeletal symptoms and signs were documented in 22 (25%) of the patients. Thirteen patients developed severe or moderately severe low back pain during their illness, two with radiological evidence of a septic discitis or vertebral osteomyelitis. Two patients developed polyarthralgia/arthritis, four had septic arthritis (all with acute Staphylococcus aureus endocarditis), three developed severe loin pain, two acute gout, two had severe buttock pain and sacroiliac joint tenderness and two each developed disabling jaw/facial pain, neck/scapular pain and flank pain respectively. Five patients presented initially to the orthopaedic or rheumatological unit for management of their musculoskeletal symptoms. Four of seven patients with Streptococcus bovis endocarditis demonstrated prominent low back pain supporting a previously noted association between this organism and back symptoms. Furthermore, in one patient who had three separate episodes of endocarditis involving three different organisms, florid back symptoms were only seen in the infective episode involving Streptococcus bovis. PMID- 1411085 TI - Changes in clinical features of patients with systemic lupus erythematosus followed prospectively over 2 decades. AB - In the past decades the general concept of the disease course and the prognosis of systemic lupus erythematosus (SLE) has changed dramatically. The improvement in prognosis of our SLE patients is often said to be related to the growing awareness of the disease. This study focussed on whether or not the clinical features at the onset of the disease, and at diagnosis, and the clinical course as well as the age at the onset of the disease had changed during the past decades. No obvious differences were observed in the age at the onset of the disease or in the age at diagnosis. Of the 22 clinical signs studied, only the prevalence of Raynaud's phenomenon at the onset of the disease had increased during the past 20 years. At diagnosis, the prevalence of oral ulcers and false positive syphilis test had decreased. Only small differences in the type but not in the number of exacerbations were observed; in the past 20 years, the prevalence of renal involvement increased from 20% to 43%. However, this was not significant. Our results did not support the theory that during the past 2 decades the disease had changed in its expression, neither did we find that the disease is presently diagnosed at an earlier age, as would be expected from the increased awareness of the disease. PMID- 1411086 TI - Cyclosporin A in a pregnant patient affected with systemic lupus erythematosus. AB - Few data regarding the use of cyclosporin A (CyA) in pregnancy are available and those available refer mainly to transplant recipients and not to patients with connective tissue diseases. We report the case of a patient with systemic lupus erythematosus (SLE), taking CyA before, during and after her pregnancy at a dose of 4 mg/kg per day. CyA was effective in controlling SLE activity and no side effects were observed in mother or baby. The lack of teratogenicity in this case was in keeping with previous reports in experimental systems, animals and human transplant recipients. If our observation is confirmed by further studies, CyA might become useful in the treatment of pregnant patients with SLE. PMID- 1411087 TI - Palmar fascial thickening and contractures of fingers resembling arthritis--a paraneoplastic symptom? AB - A 59-year-old women presented with contractures of the fingers of both hands 11 months before a diagnosis of an ovarian carcinoma with paraaortic lymph node metastases was made. We suggest that the contractures, which were associated with palmar fascial thickening and which clinically resembled arthritis, might have been a paraneoplastic sign. PMID- 1411088 TI - AB0 and Lewis blood groups in reactive arthritis. AB - In this study we evaluated secretor status in patients with reactive arthritis. Previous evidence indicates that non-secretion of AB0 and Lewis blood group antigens to saliva and other secretions is associated with susceptibility to certain bacterial infections and certain diseases with suspected autoimmune etiology. Secretor status can be determined based on the Lewis phenotype. We studied AB0, Lewis and Rhesus blood groups of 54 patients with previous reactive arthritis, 26 of whom had uroarthritis and 28 of whom had arthritis after enteric infection. Furthermore, 25 patients with uncomplicated yersiniosis and 57 healthy controls were studied. We did not find any correlation between secretor status and reactive arthritis or gastroenteritis due to Yersinia. AB0 blood group antigen B appeared to be protective against uroarthritis. PMID- 1411089 TI - Survival in patients with systemic lupus erythematosus in India. AB - Survival in patients with systemic lupus erythematosus (SLE) in developed countries has improved considerably over the last 2 decades. In India, however, survival in patients with SLE reported 5 years ago from this tertiary referral centre was very poor. The present study was conducted to examine trends, if any, towards improvement in the survival of patients with SLE attending the same centre during the period 1981-1990. No statistically significant change in survival was noted. It appears that improvement in the survival of SLE patients would require an overall improvement in the standard of medical care in India. PMID- 1411090 TI - Clinical significance of rheumatoid factor isotypes in seropositive arthritis. AB - In this cross-sectional study a comparison was made of rheumatoid factor (RF) isotypes in 203 RF positive patients with arthritis. Of these, 129 had rheumatoid arthritis (RA) and 74 a milder disease that would formerly have been classified as probable RA. The majority (74%) of the RA patients had elevations of two or three RF isotypes compared with only 34% of the patients with the milder form of arthritis. A striking feature was that combined elevation of IgM RF and IgA RF was found in 67% of the RA patients compared to only 20% of the patients with milder arthritis who most frequently had an isolated elevation of IgM RF (41%). RA patients with an isolated elevation of IgA RF were younger and had a shorter disease history than RA patients with an isolated elevation in IgM RF or a combined elevation of IgA RF and IgM RF. The prevalence of raised IgM RF was, furthermore, found to increase with age and disease duration. We conclude that a raised level of IgA RF is an adverse phenomenon in patients with seropositive arthritis while patients with an isolated increase in IgM RF may be expected to experience a relatively mild disease course. PMID- 1411091 TI - Scanning electron microscopic evaluation of the arthritis in MRL/lpr mice. AB - The articular surfaces of disarticulated knee joints from MRL/lpr and MRL/n mice, aged 4-33 weeks were examined by light microscopy (LM) and scanning electron microscopy (SEM). Light microscopy did not reliably predict SEM findings. Most of the abnormalities detected by SEM were related to surface disruption of articular cartilage. However, areas of articular cartilage covered by tightly adherent non confluent monolayers of stellate-shaped cells with intertwining cytoplasmic processes were observed. In these areas the integrity of the underlying cartilage matrix was disrupted, with exposure of collagen fibers. These findings suggested that outgrowth of proliferating synovial cells in the joints of arthritic MRL/lpr mice may lead to cartilage destruction. PMID- 1411092 TI - Analysis of glycosaminoglycans in human serum after oral administration of chondroitin sulfate. AB - Chondroitin sulfate was administered orally to six healthy volunteers, six patients with rheumatoid arthritis and six patients with osteoarthritis. Blood was collected at intervals before and after treatment and the glycosaminoglycan concentration was analyzed in serum using a sensitive assay based on the metachromatic reaction with 1,9-dimethylmethylene blue. The glycosaminoglycan concentration in serum before and after ingestion of chondroitin sulfate was statistically unchanged in all of the subjects studied. We suggest that chondroprotection by orally administered chondroitin sulfate is a biologically and pharmacologically unfounded theory. Any possible benefit to osteoarthritic patients after ingestion of chondroitin sulfate should be sought at the gastrointestinal rather than at the plasmatic or articular cartilage level. PMID- 1411093 TI - Lymphokines and soluble interleukin-2 receptors in juvenile chronic arthritis. Clinical and laboratory correlations. AB - Serum levels of interleukin (IL)-2, interferon gamma (IFNg) and soluble IL-2 receptors (sIL-2R) were determined in sera from 34 patients with poly- or pauciarticular juvenile chronic arthritis (JCA) by use of enzyme-linked immunosorbent assays (ELISAs). Levels of sIL-2R were elevated in the group of patients compared with those of healthy children and correlated significantly with several parameters of clinical activity, including the functional capacity, joint score, visual-analogue score and erythrocyte sedimentation rate (ESR). Serum IL-2 levels were also elevated in the JCA patients, correlating with the patients functional capacity. Serum levels of IFNg were below the detection limit of the assay. Our data supported the notion that T-cell activation plays a role in the immunopathologic processes leading to clinical JCA. PMID- 1411094 TI - Arthritis community education by leather puppet (wayang kulit) shadow play in rural Indonesia (Java). AB - As part of the WHO/International League Against Rheumatism (ILAR) sponsored community organized programme for the control of rheumatic disease (COPCORD), an arthritis community education programme (ACE) was undertaken utilizing the traditional form of entertainment in a rural area in Central Java-the wayang. The point prevalence rate of musculoskeletal complaints was estimated in 4683 men & women aged 15 years and over by house-to-house interviews. From 1105 respondents recording recent musculoskeletal pain, 844 were randomly selected and half the latter attended a puppet shadow play (wayang) incorporating the ACE. The other half, matched for age, sex and educational level who did not see the play, served as controls. A questionnaire containing biphasic choices of correct or incorrect ways of performing activities of daily living (ADL) to minimize musculoskeletal problems was administered to the whole group before, 1 month and 6 months after the wayang. Increased knowledge of correct ways of performing ADL (correct ADL) in the intervention group compared with the control group at 1 and 6 months after wayang was significant (P less than 0.05). Comprehension of correct ADL following the wayang could be demonstrated even in subjects who were illiterate and those who had attended primary school only. Retention of knowledge at the 6 month assessment declined more markedly in the illiterate group. ACE by wayang was shown to be feasible and effective in transferring knowledge on ADL to people with musculoskeletal problems in the sample population in Java. This effect could be shown even in the poorly educated section of the community.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411095 TI - Influence of topical steroid treatment on maxillary sinusitis. AB - The clinical efficacy and adverse effects of budesonide administered as a nasal aerosol in addition to sinus washings and erythromycin therapy was assessed by comparison with placebo in a randomized, double-blind study of 40 patients with chronic or recurrent maxillary sinusitis. Most of the patients had been referred for operative treatment. Corticosteroid therapy, 400 micrograms daily, or placebo was continued for 3 months. Budesonide and antral irrigations reduced nasal symptoms more effectively than placebo, and there was a significantly greater reduction in facial pain and sensitivity in the budesonide group than in the placebo group. During the treatment period, mucosal thickening as evaluated by radiology decreased more clearly in the budesonide group than in the placebo group, but the difference did not reach statistical significance. The most frequently isolated bacteria were Staphylococcus aureus, Staphylococcus epidermidis and Haemophilus influenzae. Only 2 of 20 Haemophilus strains were beta-lactamase producers. The cellular picture was dominated by neutrophils in all secretions. There was no significant difference in clinical outcome between the two groups. Topical steroid therapy did not cause any adverse effects. PMID- 1411096 TI - The value of high-resolution CT-scan for diagnosis of infectious paranasal sinuses disease and endonasal surgery. AB - Since 1986 the high resolution CT in two planes is part of our preoperative diagnostic program for patients with chronic rhinosinusitis, acute, complicated rhinosinusitis and polyposis nasi. The importance of the CT for diagnosis, localization, and planning the operation shall be demonstrated. PMID- 1411097 TI - Nasal sensitization of dairy farmers to bovine epithelial and urinary antigens. AB - Nineteen dairy farmers with nasal symptoms associated with working in cowhouses participated in the study. Nasal challenge with bovine epithelial antigen (BEA) and bovine urinary antigen (BUA) was made before and after the indoor feeding season. Nasal challenge made before the indoor feeding season with BEA was positive in five patients and three of them showed positive reaction in nasal challenge also with BUA. After the indoor feeding season the results in nasal challenge with BEA were approximately equal to BEA and four of them showed positive response in nasal challenge to BUA. However, we did not find any significant increase in sensitivity in nasal challenge to BEA or BUA after the indoor feeding season. In addition to these patients, two patients who were excluded from nasal challenge before the indoor feeding season showed positive results in nasal challenge after the indoor feeding season with both BEA and BUA. Our results suggest that BUA in addition to BEA may have significance to nasal symptoms. PMID- 1411098 TI - Nasal mucosa reaction. A model for mucosal reaction during challenge. AB - Rhinological symptoms in aspects of hyperreactivity and allergy are increasing problems. Previous reports on this subject are based on studies of airway obstruction (rhinomanometry), secreted substances during challenge, and symptom scores. To be able to define and evaluate the pathological reactions in nasal hyperreactivity and allergy, it is necessary to find principles to describe and standardize the reactions of the healthy nasal mucosa. The aim of this study was to examine congestion of the nasal mucosa in healthy volunteers. Existing measuring methods, in this aspect, are either indirect or not accurate enough for this purpose. With the development of rhinostereometry, an optical measuring method, it is possible to record nasal mucosa congestion with high accuracy. A nasal challenge test was made in healthy volunteers with gradually raised concentrations of a histamine solution, which was applied to the inferior concha on the right side. Recordings of the mucosal congestion were made with rhinostereometry. We found that it is possible, with statistical significance, to standardize the reactions of the healthy nasal mucosa: There is no congestion more than 0.4 mm with a histamine concentration of less than 4 mg/ml (p less than 0.05); congestion of more than 0.4 mm is present at histamine concentrations of 16 mg/ml (p less than 0.05). PMID- 1411100 TI - Medico-legal aspects of sinus surgery. PMID- 1411099 TI - Hereditary haemorrhagic teleangiectasia: unsuccessful treatment with the flashlamp-pulsed dye laser. AB - In seven patients with hereditary haemorrhagic teleangiectasia (HHT) only one patient had lasting benefit from treatment with the flashlamp-pulsed dye laser. In seven other patients who had received other treatment before, none had any observable effect of this laser. The flashlamp-pulsed dye laser therefore does not seem to be effective in the treatment of nasal teleangiectasias. PMID- 1411101 TI - Nasal vascularization: experiences using the microcorrosion technique in human foetuses. AB - The authors have studied the three-dimensional aspect of the vascular architecture of the nasal mucosa, using the microcorrosion method followed by scanning electron microscopical observation of casts of the vascular networks in both the septum and the lateral part of the nose. Batson's compound was introduced into the vascular system through the ascending aorta, in order to obtain a replica of the nasal mucosa vessels. Twelve- to 24-week-old foetuses obtained from spontaneous abortions were used for this purpose. PMID- 1411102 TI - Fractured-nose reduction under local anaesthesia. Is it acceptable to the patient? AB - This article examines patients' acceptance of fractured-nose reduction under local anaesthesia, both objectively and subjectively. At each stage of the reduction the level of the discomfort, the patients' experiences were recorded. The success rate of complete reduction of the nasal fracture was found to be 71% and this was similar to that obtained in other studies that have used general anaesthesia. An overall level of discomfort for the procedure in terms a layman can understand was obtained by comparing the manipulation with that of having a tooth filled at the dentist. Sixty-three percent of the patients said that the nasal fracture reduction was no worse or the same as a dental filling. Our study showed that 96% of patients would be willing to undergo the same local anaesthetic procedure if they fractured their nose a second time. We conclude that it is possible to reduce the majority of fractured noses adequately with little inconvenience to the patient under local anaesthesia, and so we recommend that this procedure should be considered in the first-line treatment of the displaced fractured nose. PMID- 1411103 TI - Nasal mucociliary clearance and resolution of otitis media with effusion in children following adenoidectomy. AB - Numerous workers have studied the relationship between nasal mucociliary clearance and adenoid removal in terms of nasal function. This study was performed to investigate the role of preoperative saccharin clearance time and velocity determination in selecting children with established otitis media with effusion (OME) for adenoidectomy. Testing was not found to be particularly reproducible and there was no statistically significant relationship between mucociliary parameters and the otoscopic resolution of effusion. PMID- 1411104 TI - [Treatment of asthma]. PMID- 1411105 TI - [Holistic treatment of asthma by the pediatrician]. PMID- 1411106 TI - [Anemophilous fungi: viability and allergenicity]. AB - Three strains of anemophilous fungi (Alternaria, Rhizopus and Monilia) from different genera were studied. We found that the liquid Sabouraud and culture media used in this study lost nutrients after seven days of strain growth, without affecting their viability. This was proven when the fungi were reseeded at 15 and 60 days. Extracts from supposedly sensible patients were developed using intradermoreaction skin tests, finding no significant differences among the results obtained from these tests. We recommended further studies with more prolonged growth periods (90, 120, 180 or more days) to see whether this incides on the viability and allergenicity of the anemophilous fungi. PMID- 1411107 TI - [Effectiveness of sodium cromoglycate in the reduction of bronchodilator doses in asthmatic patients]. AB - Thirty asthmatic patients, ages ranging from 6 to 72 years, who were submitted to a 14 weeks clinical evaluation, were studied measuring the severity of dysnea, coughing, expectoration and wheezing. Sodium chromoglycate (SCG) was administered in aerosol starting the second week of the study and the doses of bronchial dilators was reduced starting the fourth week, with a 25% decrease in the total established initial dosage, every two weeks. In this study, SCG showed to be useful in decreasing symptoms caused by bronchial hyperreactivity and the use of bronchial dilators in 70% of asthmatics who react with the presence of just one risk factor (cold, the most frequent). PMID- 1411108 TI - [In vitro and in vivo acari tests]. AB - We studied 40 children with one o more perennial allergic diseases (bronchial asthma, allergic rhinitis, and/or atopic dermatitis) to assess the value in our country of in vivo and in vitro tests more frequently used in the diagnosis of allergy, such as total serum IgE, specific allergen IgE (RAST) and prick skin test in patients sensitives to D. pteronissinus, D. farinae or both. All patients had positive prick skin tests. Total serous IgE was elevated in 95% of cases with poor correlation coefficient (r) between prick skin test reactivity and total serous IgE concentration with no statistical significance. On the other hand, 95% of patients showed a positive RAST with a correlation coefficient of 0.31 (p less than 0.05). We concluded that in our country clinical history and prick skin tests are sufficiently accurate in a reasonable way to make a diagnosis of allergic etiology in patients sensitives to mites of the house dust. PMID- 1411109 TI - [Intrahospital epidemic outbreaks. Their study and control]. PMID- 1411110 TI - [Peridual morphine and postoperative pain]. PMID- 1411111 TI - [The quality of the public water supply. A study in Albacete]. PMID- 1411113 TI - [Vaccination against influenza in groups at risk]. PMID- 1411112 TI - [Influenza, an important health problem]. PMID- 1411114 TI - [Txagorritxu Hospital at the service of Alava]. PMID- 1411116 TI - [Work hours: their repercussions on health]. PMID- 1411115 TI - [Our experience with Anna]. PMID- 1411117 TI - [The cancer patient. The other parameters of care]. PMID- 1411118 TI - [Anthropology applied to feeding and nutrition policies]. PMID- 1411119 TI - [Continuing education. 71. Concepts of administration]. PMID- 1411121 TI - [Vaccines: an instrument of health]. PMID- 1411120 TI - [A waste-disposal unit (macerator)]. PMID- 1411122 TI - Abnormal auditory brainstem responses and cochlear pathology in rats induced by an exaggerated styrene exposure regimen. AB - Groups of 12 male 42-day-old rats were exposed to 0 or 800 ppm styrene vapors for 14 hr/day, 5 days/week for 3 weeks. Tone-pip auditory brainstem responses (ABRs) at 4, 8, 16, and 30 kHz were obtained after the last exposure. ABRs were minimally affected at 4 kHz and moderately to severely affected at 8, 16, and 30 kHz as indicated by waveforms which had a decreased amplitude and increased latency as compared to the controls. Missing outer hair cell(s) were evident in the basal and lower middle turns of the organ of Corti. Outer hair cell loss was least in the first row and greatest in the second and third rows. Occasional inner hair cells were also missing in regions of severe outer hair cell loss. The distribution of hair cell loss within the cochlea was consistent with the pattern of ABR alterations. These data document mid-frequency auditory dysfunction in styrene-exposed young adult rats with significant damage to the organ of Corti following an exaggerated styrene exposure regimen. PMID- 1411123 TI - Light microscopic and ultrastructural pathology of seminiferous tubules of rats given multiple doses of Pasteurella multocida group D protein toxin. AB - Male Holtzman rats were given subcutaneous doses of a purified Pasteurella multocida group D heat-labile toxin on alternate days for up to 22 days. Rats were necropsied at 18 days or 36 days (14 days after last dose of toxin) or when moribund, and testicles were taken for histologic and ultrastructural examination. Other selected tissues, including liver and spleen, were taken for histologic examination. Histologically, testicular and splenic lesions occurred more consistently and at much smaller doses when compared with lesions in other target organs such as liver. Testicular and splenic lesions were present in all rats (6/6) given 0.8 micrograms/kg toxin and were seen in some rats (1/6) given as little as 0.2 micrograms/kg toxin. Only 3/6 rats given 0.8 micrograms/kg toxin had hepatic lesions; no hepatic lesions were seen at doses of 0.2 micrograms/kg. Testicles from toxin-treated rats were smaller and weighed less than controls. Seminiferous tubules were moderately dilated and lined by polygonal sertoli cells. The normal spermatogenic maturation sequence and mature spermatids were absent, and many tubules contained multinucleate spermatocytes. Severely affected tubules were necrotic and mineralized. Ultrastructurally, there was necrosis of adluminal spermatocytes, multinucleate cell formation, and spaces between Sertoli cell plasma membranes. Testicular lesions were similar to those described for vitamin D-deficient rats, vitamin A-deficient rats, vasectomized rats, and rats given intravenous tumor necrosis factor; however, rats given lethal doses of toxin did not have elevated levels of TNF alpha activity. PMID- 1411124 TI - Liver tumors in male rats following treatment with glucocorticosteroids. AB - Male rats treated with either budesonide, prednisolone, or triamcinolone acetonide in drinking water for up to 104 weeks developed slightly increased incidences of basophilic foci, and significantly increased incidences of combined hepatocellular adenomas/carcinomas as compared to controls. Based upon reduced body weight gains and survivals, the doses administered were considered to be toxic. It was concluded that the positive findings represented a class effect, and probably involved glucocorticoid receptors. PMID- 1411125 TI - Histological sectioning of the rodent larynx for inhalation toxicity testing. AB - In rodents, the larynx is a major site of histopathologic alteration following inhalation exposure to particulates, vapors, and aerosols. Specifically, the epithelial lining of a narrowly delineated region on the ventral floor of the larynges of rats and mice appears to be especially vulnerable to inhaled materials, and is recognized as a preferred site for histopathological evaluation in inhalation studies. This site is located at the base of the epiglottis, cranial to the ventral laryngeal diverticulum (ventral pouch). The presence of underlying seromucinous glands is critical for histologic identification of this site. We report a histologic sectioning technique, using the ventral laryngeal diverticulum as the anatomical landmark, to obtain tissue sections from this area of predilection in rats and in mice. PMID- 1411126 TI - Spontaneous renal neoplasms in aged Crl:CDBR rats. AB - Primary neoplasms of the kidneys occurred in 11/682 male (1.6%) and 2/694 female (0.3%) Crl:CDBr strain Sprague-Dawley rats. Eight of 13 neoplasms were of mesenchymal origin and 5 of 13 were epithelial. Five neoplasms were lipoma (3) or liposarcoma (2). Three of 13 were either hemangioma (1) or mesenchymal tumors (2). The epithelial neoplasms were carcinomas. There was no microscopic evidence of metastasis among those neoplasms judged malignant on morphologic criteria. The overall natural incidence in males was nearly double that compiled for this strain while in females the incidence was similar to that reported for other females. PMID- 1411127 TI - Prednisone is not a mouse carcinogen. AB - The carcinogenic potential of prednisone, a synthetic corticosteroid used as an anti-inflammatory and immunosuppressive agent, was investigated by feeding it to Crl:CD-1(ICR) mice (50/sex/dose) at doses of 0.25, 0.50, 1.0, and 5.0 mg/kg/day for 18 months. Prednisone did not significantly increase the incidence of neoplasms (p less than or equal to 0.05); on the contrary, it significantly decreased the incidence of hepatocellular tumors (p = 0.002 in males, p = 0.027 in females), male lacrimal/Harderian gland tumors (p = 0.05), female pulmonary adenomas (p = 0.047), female endothelial cell tumors (p = 0.035), and female lymphosarcomas (p = 0.02). This study suggests that long-term (lifetime) prednisone use does not increase cancer risk and may actually reduce it. PMID- 1411128 TI - Stereological evaluation of altered hepatocellular foci in control Wistar rats. AB - Quantitative evaluation and stereological analysis of altered hepatocellular foci (AHF) were performed on hematoxylin and eosin-stained (H&E) liver sections from control Wistar rats from 9 2-yr carcinogenicity studies conducted between 1981 and 1991. Morphologic criteria previously described were used to classify AHF in H&E stained livers into basophilic, eosinophilic, clear, mixed, or vacuolated cell foci. Hepatocellular adenomas were seen in 1.6% of control rats and carcinomas were seen in 0.2%. AHF were diagnosed in 20% of control Wistar rats and were seen only in rats dying after 47 weeks. Basophilic foci were the most common AHF seen; incidences of tigroid and diffuse basophilic AHF were similar. Vacuolated foci were not identified in any rat. The mean number of AHF per cubic centimeter of liver was 101. The mean AHF volume varied from 0.002-0.048 mm3 and the mean volume fraction ranged from 0.005-0.026%. Compared to AHF in aged control Fischer 344 rats, AHF in control Wistar rats were fewer and smaller. PMID- 1411129 TI - Testicular damage caused by inhalation of ethylene oxide in rats: light and electron microscopic studies. AB - Although testicular damage caused by ethylene oxide vapor (EtO) has been previously reported, the morphological changes occurring in seminiferous tubules remain unclear. We examined the time course of the testicular lesion induced by EtO in order to clarify its morphogenesis. Wistar rats were exposed to 500 ppm EtO for 6 hr per day, 3 times per week for 2, 4, 6, or 13 weeks through inhalation. In the 2-week exposure group, Sertoli cells often showed condensation and retraction of the cytoplasm, and dilatation of the endoplasmic reticulum (ER). In apical Sertoli cells, processes which encapsulated the heads of elongate spermatids, ectoplasmic specializations, and tubulobulbar complexes were often deformed and many elongate spermatids were degenerated. In the 4- and 6-week exposure groups, many degenerated Sertoli cells were present, and deformed germ cells, sometimes with multinucleation, appeared to make direct contact with each other without interlocation of Sertoli cell lateral processes. A few scattered immature Sertoli cells were evident in the 6-week exposure group. In the 13-week exposure group, seminiferous tubules containing almost all types of germ cells reappeared, mixed with atrophic tubules containing Sertoli cells only. In the former tubules, Sertoli cells often possessed regularly regenerated lateral processes, which were interposed between germ cells. These results indicate that the germ cell damage may be associated with damage to Sertoli cells. In spite of the intermittent exposure, focal regeneration of Sertoli cells appeared after 6 weeks of exposure to EtO and preceded patchy recovery of germ cells. Therefore, the data suggest that Sertoli cell regeneration may permit regeneration of germ cells. PMID- 1411130 TI - Histologic methods and interspecies variations in the laryngeal histology of F344/N rats and B6C3F1 mice. AB - The relatively high incidence and variety of lesions induced in the upper respiratory tract of rodents by inhalation of xenobiotics has resulted in considerable attention given to the microscopic anatomy of this area. Specific areas of the rodent laryngeal mucosa appear to be more sensitive to inhaled materials and more likely to contain cellular changes in response to injury. These include the epithelium covering the base of the epiglottis, ventral pouch, and the medial surfaces of the vocal processes of the arytenoid cartilages. There are few good landmarks for trimming rodent larynges to get consistent and accurate sections through these target areas. We have obtained consistently reproducible results by cutting transversely through the easily palpable cricothyroid notch and embedding the entire larynx anterior to this in paraffin with the cut surface against the face of the block. Multiple sections are cut from the caudal larynx toward the epiglottis, unstained sections examined microscopically for orientation, and sections from target areas selected for staining and histopathologic examination. Routine use of these methods for preparation and microscopic examination of sections of the larynx has revealed some variations in normal laryngeal anatomy between Fischer 344 (F344/N) rats and B6C3F1 mice. PMID- 1411131 TI - Effects of corn oil, time-related changes, and inter-laboratory variability on tumor occurrence in control Fischer 344 (F344/N) rats. AB - Survival, body weight, and site-specific tumor rates in untreated, corn oil gavage, and water gavage control Fischer 344 (F344/N) rats from 88 National Toxicology Program (NTP) long term carcinogenicity studies were evaluated to determine which factors were primarily responsible for inter-study variability. For male rats, previously-reported decreases in leukemia and increases in body weight, survival, and pancreatic acinar cell tumors attributable to corn oil gavage were confirmed. Corn oil did not appear to affect tumor rates in female rats. The gavage technique per se did not appear to influence tumor rates in rats of either sex. Previously reported time-related increases in certain site specific neoplasia in control rats appeared to have stabilized in recent years, but control tumor rates are still much greater than those seen a decade ago. More recent studies continue to show increasing rates of leukemia and mammary gland tumors and decreasing survival. Female rats also continue to show time-related increases in maximum mean body weight. Inter-laboratory variability in body weight and in the rates of a number of site-specific neoplasms were also significant. High mean body weights in control groups were found to be associated with increased rates of mammary and pituitary tumors. Our evaluation supports the view that if historical control data are to be utilized in the interpretation of experimental results, primary emphasis should be given to lab and route of administration-specific tumor rates for studies that are contemporary to the study under evaluation. It also suggests that certain experimental design changes (e.g., dietary modifications) may be needed to reduce tumor rates and to increase survival. PMID- 1411132 TI - Hepatic morphologic and biochemical changes induced by subacute cocaine administration in mice. AB - The initial event and site of cocaine-induced hepatic injury have not been elucidated. In an attempt to identify the minimal effective dose and the site of injury, we have examined the livers of mice exposed to small daily doses of cocaine, using morphological and biochemical methods. All doses of cocaine greater than 5 mg/kg were able to cause significant elevation of serum glutamic pyruvic transaminase. Light microscopy revealed a progression of centrilobular necrosis as the dose increased from 10-30 mg/kg. The initial morphologic changes observed prior to necrosis included aggregation of intermediate filaments and dilation of rough endoplasmic reticulum with loss of ribosomes. Immunohistochemistry, using antibodies to cytokeratins, showed staining of individual hepatocytes in livers from cocaine-treated animals but not in controls. In contrast to earlier reports, we found little, if any, disruption of mitochondria. In vitro, the direct application of cocaine, norcocaine, and N hydroxynorcocaine on isolated mitochondria had no effect on the ADP:O or respiratory control ratios, at concentrations up to 2.0 mM. Our studies demonstrate that any early cellular alterations in cocaine-induced hepatic injury are manifested in intermediate filaments and endoplasmic reticulum with no evidence of mitochondrial involvement. PMID- 1411134 TI - Pathogenesis of blood-filled cavities in estrogen-induced anterior pituitary tumors in male Sprague-Dawley rats. AB - The formation of blood-filled cavities in developing tumors of the anterior pituitary of estrogen-treated male Sprague-Dawley rats was studied in a serial sacrifice experiment. Two treated and 2 control rats were killed at each of 15 time points ranging from 7-272 days after sc implantation of an estradiol-17 beta pellet. The pituitaries were examined using light and electron microscopy. Changes at 7-9 days after implantation included epithelial cell swelling and trabecular arrangement. At 11-13 days, epithelial cells were further enlarged. Arrangement of epithelial cells in islands and endothelial degeneration were first seen at this interval. Also, any sinusoids were distended, whereas some were compressed by swollen epithelial cells. At 16-81 days, scattered necrotic and immature epithelial cells were present, and cell size decreased. Endothelial degeneration and both distended as well as compressed sinusoids were more prominent at this time. Loss of basement membrane was first seen during this interval. At 114-133 days, small hemorrhagic areas partially lined by epithelium were first seen; sinusoidal compression, endothelial necrosis, and loss of basement membrane were more frequent, but there was less sinusoidal distention. Between 150 and 272 days, epithelial cells were increasingly pleomorphic and arranged in nodules, and there was an increase in number and size of the hemorrhagic areas. Sinusoidal compression, endothelial necrosis, and loss of basement membrane were abundant, whereas sinusoidal distention had almost disappeared at this interval. Local compression of sinusoids and perhaps compression of pituitary surface veins due to epithelial cell swelling, were thought to play a primary role in the development of ischemic endothelial damage leading to loss of endothelial lining and basement membrane, and eventually to the formation of blood-filled spaces partially lined by epithelial cells. PMID- 1411133 TI - Drug-induced hepatic microgranulomatosis in cynomolgus monkeys. AB - This report discusses a unique drug-induced hepatotoxicity in cynomolgus monkeys treated orally with a novel potassium sparing experimental diuretic, [2,6-bis(4 chlorophenyl)-4-pyridinecarboxylic acid]. Groups of 6 adult male and female monkeys were treated orally with vehicle diluent, modified vehicle #122 or a suspension of the drug at 5.0, 12.5, or 32.0 mg/kg/day for 2 weeks. Another group of 5 monkeys were treated orally with 25.0 mg/kg/day of the drug for 2 weeks. Disposition of the drugs was evaluated in 2 monkeys in the later group that received 27.4 mg/kg of radiolabelled drug on the 1st and last day of dosing. Hepatic toxicity was characterized biochemically, light and electron microscopically, histochemically, immunocytochemically, and toxico-kinetically. Conjugated serum bilirubin, alanine transaminase, and aspartate transaminase levels were increased in monkeys treated with over 12.5 mg/kg/day of the diuretic. The periacinar hepatic plates of monkeys treated with 25.0 or 32.0 mg/kg/day were distorted by accumulation of PAS and oil red-O positive multinucleated Kupffer cells. The cytosol of these cells was expanded by phagolysosomes containing granular materials of varying electron densities. Granular electron dense materials were also in endothelial cells and bile canaliculi. Fatty change, cholestasis, and rare piecemeal hepatic necrosis were minimal. The drug was primarily excreted through urine. Plasma concentration and half life of the drug were increased with multiple dosing. The highest concentration of unexcreted parent drug was in the liver. Drug-induced noninflammatory hepatic microgranulomatosis, apparently caused by sequestered drug-lipid/mucopolysaccharide complex in the phagocytic cells of the liver, can occur in any species, including humans, if orally administered xenobiotics are presented to the liver in particulate form. PMID- 1411135 TI - Histopathological effects in Poecilia reticulata (guppy) exposed to methyl mercury chloride. AB - To evaluate the usefulness of histopathology in aquatic toxicity testing, studies were carried out on the small freshwater fish Poecilia reticulata (guppy) following aqueous methyl mercury chloride exposure. Fish were exposed to concentrations of 0, 1.0, 1.8, 3.2, 5.6, or 10 micrograms/L for 1 and 3 months. Histopathological changes included the occurrence of multiple granulomas in various tissues, in particular, the integument and orbit. These changes were accompanied by hyperplasia of monocytopoietic interrenal tissue, and hepatocellular change which was confirmed by morphometry. The latter findings were probably a result of monocyte "consumption" by granulomas, and hepatic synthesis of ("stress") proteins, respectively. The bile duct and, focally, the proximal intestine, showed hyperplasia of the epithelium. In the testis of sexually mature fish (3-month study), degeneration and necrosis of sperm occurred, with severe cases exhibiting Sertoli cell hypertrophy, interstitial inflammation, and absence of mature sperm. Epidermal mucous cells disappeared in the highest concentration used, and, after 3 months, clusters of undifferentiated basophilic cells were seen in the gas gland, which occasionally were suggestive of malignant growth. The changes in the kidney tubules were characterized by degeneration and necrosis of single cells which also showed mitotic figures. This is considered a result of the mitosis-disturbing activity of methyl mercury (MeHg). It is concluded that MeHg has effects on various target organs in guppies with the occurrence of granulomas as the most sensitive indicator, yielding a no observed-effect concentration (NOEC) of 1.0 micrograms/L. In contrast to mammalian species, no morphologic evidence for neurotoxicity was found. PMID- 1411137 TI - Evidence that chemical carcinogens interfere with specific regeneration controlling mechanisms of urodeles. AB - The present investigation was conducted in an attempt to understand the interrelationships between carcinogenesis and regeneration. The aim was to find out whether chemical carcinogens constitute a class of agents specifically interfering with the normal developmental process during amphibian limb regeneration. To achieve this, the potent chemical carcinogens N-methyl-N'-nitro N-nitrosoguanidine (MNNG) and N-nitrosodimethylamine (DMN) were inserted at a position slightly proximal to the blastema of regenerating Triturus cristatus forelimbs. The results indicate that, sometimes, the two developmental parameters, growth rate and morphogenesis, were differently affected depending on the treated limb and the carcinogen used. The effect of DMN on regenerative growth rate was negligible, but morphogenesis was highly impaired. Similarly, MNNG-treated stumps displayed abnormal regenerates in both forelimbs, whereas growth rates were significantly affected only in the right forelimbs. The findings are discussed in the framework of the relevant hypotheses. PMID- 1411136 TI - Rat urinary bladder hyperplasia induced by oral administration of carbonic anhydrase inhibitors. AB - The carbonic anhydrase inhibitors, acetazolamide and MK-0927, were given by oral route to male Sprague-Dawley rats at 200 mg/kg/day and 25 mg/kg/day, respectively, for up to 4 weeks. Sequential necropsies were performed and urinary bladders were examined by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Similar urinary bladder changes were seen with both compounds. SEM evidenced slight multifocal urothelial changes consisting of cell swelling, dissociation, degeneration, and exfoliation after 3 and 5 days of treatment. After 2 and 4 weeks of treatment, elevated or leafy microridges on the luminal cell surfaces were seen together with foci of swollen cells. After a 2-month-recovery-period, the urothelial surfaces were normal. LM and TEM showed multifocal vacuolation of the urothelium associated with inflammation of the underlying lamina propria after 3 and 5 days of treatment. Cellular hypertrophy and hyperplasia of the transitional epithelium was seen after a 5-day treatment, persisted without increasing severity after 2 and 4 weeks of treatment, and totally regressed after the recovery period. It was concluded that, in the rat urinary bladder, oral administration of acetazolamide and MK-0927 induced early degeneration and inflammation followed by epithelial regeneration, resulting in a reversible hyperplasia of the transitional epithelium. PMID- 1411138 TI - Quantitation of metastatic tumor burden from human colon tumor xenografts using radiolabelled monoclonal antibody 17-A fragments. AB - In realistic models of human tumor xenograft metastasis, the metastatic foci arise in perivascular sites and rarely grow to sizes which are easily quantifiable by visual inspection. As an alternative approach, we have used monoclonal antibody (MAb) 17-1A F(ab')2 fragments labelled with radioiodine (125I) to study the differential accumulation of label in xenografts and metastatic tumor sites as well as in noninvolved tissues of NIH Swiss nude mice receiving HT-29 human colon tumor cells. Images of the whole-body distribution and sites of localization were determined using a pinhole-collimated Angergamma camera. Radioactivity was determined in tissue samples using a well scintillation system, and pharmacokinetics were assessed during the initial 72 h after injection of antibody fragments. The half-life of 125I-F(ab')2 fragments in the blood, 8.6 h, was similar in nontumor-bearing control and tumor-bearing mice. The half-life in subcutaneous tumor xenografts was 30.1 h. The tumor xenograft to tissue activity ratios per unit weight (radiolocalization indices) at 72 h were: blood 90, lung 65, pancreas 50, muscle 35, spleen 20, liver and mesenteric lymph node 10. All subcutaneous xenografts were successfully imaged, and images of 5 of 9 mice (55%) appeared to demonstrate the presence of metastatic tumor by differential and focal accumulation of MAb fragments after 48 or 72 h in the lung (2 cases) or abdominal cavity (3 cases). Necropsy and subsequent histological and biodistribution studies confirmed the presence of metastatic tumor in these sites and identified tumor in several additional sites. The smallest volume of metastatic tissue in liver or lung determined at necropsy which appeared to have been detected by imaging was about 20 mm3. Generally, for mice with metastatic tumors, the radioactivity per unit weight of metastatic tumor-bearing organs compared to tumor-free organs was 2- to 7-fold greater. The results indicate that a radiolocalization index of > or = 2 is generally necessary for metastatic tumor detection by imaging although this is influenced by the extent of anatomical location of the tumor. It was possible to predict the tissue distribution of the fragments from the planar image for the amounts of radioactivity (approximately 1 mCi/kg body weight) employed in this study. These results demonstrate the utility of this approach to quantitate the metastatic burden arising from human colon tumor xenografts in this experimental model. PMID- 1411139 TI - Serum markers for primary and recurrent breast cancer: BCM-EIA, CAM 26 and CAM 29. AB - Three sandwich enzyme immunoassays were used to evaluate serum from 93 women: 20 normal, 20 with benign breast disease, 22 with primary and 31 with recurrent breast cancer. Using the three assays, breast cancer mucin enzyme immunoassay (BCM-EIA) carcinoma-associated mucin antigen (CAM) 26 and CAM 29, both singly and in combination, we were unable to establish meaningful cut-offs to differentiate between patients with or without breast cancer. The sensitivity and specificity for BCM-EIA were 90% and 40%, for CAM 26, 89% and 42%, and for CAM 29, 91% and 66%, respectively. Serial serum specimens from 29 patients with recurrent breast cancer were assayed. At recurrence, an increase of 25% or more in marker level over the previous value was found in 24/29 (83%) BCM results, 14/29 (48%) CAM 26 results and 12/29 (41%) CAM 29 results. Prior to clinical detection of recurrence, stepwise increases in BCM and CAM 26 marker levels were seen up to 299 days prior to clinical detection of recurrence. We conclude that these markers may help in the early detection of recurrent breast cancer. PMID- 1411140 TI - Detection of xenogeneic anti-idiotypic antibodies specific to murine monoclonal antibody 17-1A in patients with gastrointestinal cancer. AB - Murine monoclonal antibody (MoAb) 17-1A, which reacts with an adenocarcinoma associated antigen, has recently been utilized in a phase I clinical trial for patients with gastrointestinal tract cancers in Japan. In order to analyze anti idiotypic (Id) antibodies to murine MoAb 17-1A in the sera of these cancer patients, we established a simple and specific assay. In a modified sandwich assay, normal mouse sera were utilized for neutralization of rat antimouse immunoglobulin (Ig) antibodies and reduction of their nonspecific effects. When the modified sandwich assay was applied to the sera of patients who had been treated with MoAb 17-1A, anti-Id antibodies were induced in 53% of 13 cancer patients with gastrointestinal cancers at 3-4 weeks after infusion of MoAb. PMID- 1411141 TI - Clones of a spontaneously metastatic human lung carcinoma cell line differ in their in vitro and in vivo phenotypic characteristics. AB - In order to isolate subpopulations of cells with differing metastatic capacity, a spontaneously metastatic human lung carcinoma cell line was cloned in vitro, using limiting dilution methods. The karyotypic profile, in vitro and in vivo growth as subcutaneous xenotransplants in athymic mice of 11 randomly selected clones were very similar. No consistent differences were seen in the adhesion to a variety of substrates or in the integrin profile of the few subunits examined. However, the in vivo metastatic capacities differed. Most of the isolated cell lines, in spontaneous metastasis assays, formed variable numbers of microscopically visible metastatic foci in only the lungs and lymph nodes of these animals. One of the 11 cell lines examined, TV9, was observed to form grossly visible metastases in the lungs as well as in the ovaries, pancreas and omental lymph nodes. Immunoprecipitation analyses detected a decrease in the expression of the previously described low-metastasis-associated H7 molecule within the high metastatic TV9. The low and high metastatic subpopulations thus isolated will provide a means to dissect the metastatic mechanisms of this human lung carcinoma cell line. PMID- 1411142 TI - We should all be tested for AIDS. PMID- 1411144 TI - Look Good ... Feel Better--a program for cancer patients. PMID- 1411143 TI - We turned med/surg staff into telemetry experts. PMID- 1411145 TI - Nurses assess U.S. health care. PMID- 1411146 TI - These patients truly need our help. PMID- 1411147 TI - "Here's something I want you to read". PMID- 1411148 TI - When a ventilator patient is going home. PMID- 1411149 TI - How the law protects emergency patients. PMID- 1411150 TI - Preventing food allergies. PMID- 1411151 TI - Follow ACAI guidelines if you're allergic to latex. PMID- 1411152 TI - Sometimes it's okay for nurses to show patients they care. PMID- 1411154 TI - AIDS costs didn't match insurers' fears. PMID- 1411153 TI - Here's a resource for people affected by gluten intolerance. PMID- 1411155 TI - Helping patients get back to work. PMID- 1411156 TI - Remembering Bill. PMID- 1411157 TI - When it's hot enough to kill. PMID- 1411158 TI - Diabetes complications that can cripple. PMID- 1411159 TI - Ten years later. PMID- 1411161 TI - When the liver breaks down. PMID- 1411160 TI - Can you rely on tympanic thermometers? PMID- 1411162 TI - PV shunts relieve ascites. PMID- 1411163 TI - Speak up! When silence is negligence. PMID- 1411164 TI - Teens can shape their postmenopausal years. PMID- 1411165 TI - Learn a new language. PMID- 1411166 TI - [Definition of asymptomatic biliary lithiasis]. AB - Asymptomatic biliary lithiasis can be defined as biliary lithiasis having determined no complication and no episode of biliary pain. Biliary pain is a consequence of acute increase of pressure inside the biliary tract. The increased pressure is induced by a stone transiently obstructing the cystic duct or the Oddi sphincter. In most patients, the site of the pain is epigastric. The level of the pain is high. The duration of the episode of biliary pain is usually less than 5 hours. Abdominal pain having other characteristics, dyspepsia, and headache are not related to biliary lithiasis. PMID- 1411167 TI - [Natural history of asymptomatic lithiasis]. AB - The natural history of asymptomatic gallstones, according to the best published studies, indicates that seventy per cent of the patients remain symptom-free. Nonetheless there are no clinical or morphological findings which can predict the occurrence of symptoms on a individual basis. PMID- 1411168 TI - [Management of asymptomatic lithiasis]. AB - A careful analysis of the series of patients with asymptomatic gallstones suggests that prophylactic cholecystectomy is not necessary. The purpose of this work was to try to detect subgroups of asymptomatic patients with factors predictive of symptoms or of severe complications such as acute cholecystitis, pancreatitis, or gallbladder carcinoma. Among local factors, neither the size, number or nature of gallstones, nor alterations of the walls or contractility of the gallbladder were predictive of symptoms or complications. Among general factors, neither the age or sex of patients nor associated diseases such as diabetes mellitus or recent organ transplantation were predictive of symptoms or complications. Only the few patients with a porcelain gallbladder were at high risk for gallbladder carcinoma requiring prophylactic cholecystectomy. In all other patients treatment of asymptomatic gallbladder stones is unnecessary as well as any surveillance. PMID- 1411169 TI - [Results of the treatment with biliary dissolvents]. AB - Cholesterol gallstones can be dissolved by chenodeoxycholic acid or by ursodeoxycholic acid administered orally. This treatment is subject to the following conditions: the gallbladder must be functioning; the gallstones must be radiolucent; the stones must not be too large; the main bile ducts must be patent; the cholelithiasis must be symptomatic but without severe complications. The two biliary acids are equally effective, but ursodeoxycholic acid is preferred to chenodeoxycholic acid because it is devoid of undesirable side effects. The effectiveness of treatment varies from one published series to the other, but it primarily depends on the size of the gallstones: if they are less than 5 mm wide dissolution can be obtained in 70 to 80% of the cases. After the end of treatment the bile becomes lithogenic again, and a relapse is possible; after 5 years this relapse occurs in about 50% of the patients. The position occupied by biliary acids in the treatment of gallstones is modest, owing to the conditions of their use and to the advantages of surgery, and notably laparoscopic surgery. Biliary acids are usually given to elderly people or to subjects at high risk for anaesthesia or surgery. Attempts have been made to introduce another cholesterol dissolvant, methyl-tert-butyl-ester, directly into the gallbladder by the transcutaneous-transhepatic route. The gallstones were dissolved, but the invasiveness of this technique and the potential toxic effects of this particular drug are such that the indications for this treatment are extremely reduced. PMID- 1411170 TI - [Results of extracorporeal lithotripsy in the treatment of cholelithiasis]. AB - Treatment of gallstones with extracorporeal lithotripsy includes the stones fragmentation with shock-waves and the dissolution of fragments with bile acids. It is a well-tolerated treatment than can be performed on an out-patient basis. However, lithotripsy is an effective treatment only in highly selected patients (low calculous volume, radiolucent stones, functioning gallbladder). A satisfactory clearance rate is observed only in patients with solitary stones < or = 20 mm in diameter (70-80% at one year). The stone recurrence rate seems to be low in patients who had solitary stones. PMID- 1411171 TI - [Oral dissolvents and extracorporeal lithotripsy: respective role and modalities of application]. AB - Oral dissolution therapy can be proposed to patients with symptomatic gallstones, with stones less than 15 mm diameter, in any number, without calcification, within a functioning gallbladder (i.e. opacified by oral cholecystography). In particular, it may be useful in patients aged over 70, or with a high operative risk, or who refuse surgery or general anesthesia. Extracorporeal shock wave lithotripsy (followed by oral dissolution therapy) is also indicated in symptomatic gallstones, without calcification or slightly calcified in a functioning gallbladder, when stone size is between 8-10 and 30 mm and stone number lower than 3. After successful dissolution, recurrence is observed with an incidence of 5 to 10% per year during the first five years. In case of symptomatic recurrence, retreatment is indicated. PMID- 1411172 TI - [Contact litholysis and contact lithotripsy of symptomatic biliary calculi]. AB - Contact litholysis and lithotripsy are invasive methods of gallstone destruction, since the gallbladder must necessarily be approached by the transhepatic or transperitoneal routes or through Oddi's sphincter. Both methods expose to complications which may require a corrective operation. The risk of recurrence is the same as with extracorporeal lithotripsy. Unless proved otherwise by further clinical trials, in the future these experimental methods should be used in a very small number of patients. PMID- 1411173 TI - [Cholecystectomy through laparotomy]. AB - Laparotomy cholecystectomy is the "gold standard operation". Its mortality is almost nil. Its morbidity dramatically decreased while digestive surgery was improving. Alternative therapies are to be compared to it. Indications of laparotomy cholecystectomy remain frequent today but will decrease promptly due to the functional and cosmetic benefits of coelioscopic cholecystectomy. PMID- 1411174 TI - [Celioscopic cholecystectomy]. AB - Laparoscopic cholecystectomy was born in 1987 and is now commonly performed, usually under general anaesthesia, and under the same technical conditions as conventional surgery. The operative procedure varies with the operators, but it is mandatory to evaluate the state of the bile duct by pre- or peroperative explorations. Compared with conventional surgery, the advantages of laparoscopic cholecystectomy are well known: the entire peritoneal cavity is explored; the lack of postoperative ileus makes it possible to resume normal feeding, and hence normal activity, after a short interruption; systemic and parietal complications are less frequent, but the biliary tract complication rate is higher, probably in relation to the operator's training. The indications were initially restrictive but now embrace the quasi-totality of gallstones, complicated or not, and in particular when the patient's general condition is fragile. PMID- 1411175 TI - [Incidents, accidents and limits of cholecystectomy by celioscopy]. AB - Series of coelioscopic cholecystectomy until 1991 has shown that morbidity rate of this procedure remains higher than conventional laparotomy. Complication are related to technical problems included: (a) biliary leak with a rate of 0.5%; (b) hemorrhage; and (c) digestive perforation. Contra-indication of this procedure are: cirrhosis, portal hypertension, bilio-biliary fistula and severe cholecystitis. Progress is expected with willing to open cholecystectomy; improvement of intervention, perioperative cholangiography and specific train of surgeons involved in the field of surgery. PMID- 1411176 TI - [Training for celioscopic surgery]. AB - All surgeons specialized in the digestive tract will have to use the laparoscopic approach in an unlimited number of operations. This has already been established in biliary tract surgery. Practising surgeons must learn to perform laparoscopic cholecystectomy by themselves, i.e. in a manner that is neither organized nor officially approved in France. Students in surgery benefit, as with other techniques, from team training. These two categories of surgeons should be able to receive a specific teaching in order to maintain the safety of biliary tract surgery at its high level of safety. To make sure that this is done, keeping national registers is strongly advised. PMID- 1411177 TI - [Indications for classical surgery and celiosurgery. Evaluation]. AB - Laparoscopic cholecystectomy is a novel technique resulting from the advances achieved in video-endoscopy. In the field of uncomplicated gallstones it has in a few years thoroughly altered the surgical indications, taking preference over conventional surgery and ousting extracorporeal lithotripsy. However, the risk of complications must be kept in mind, and the utmost care must be taken in training operators and in recording all cases and their complications. Nowadays, conventional cholecystectomy remains indicated when laparoscopy is contra indicated, notably in cases with tight peritoneal adhesions precluding laparoscopy. PMID- 1411179 TI - [Androgen receptor. From molecular biology to clinics]. PMID- 1411178 TI - [Medico-economic strategy for biliary lithiasis]. AB - The purpose of this study was to assess the relevance of a medico-economic evaluation of gallstones. In other words, would it be possible to define economic criteria that would permit to select the best therapeutic method whilst respecting medical ethics? The frequency of gallstones, the high consumption of goods and medical services they require and the important loss of productivity that ensues justify this approach. The medical literature and a number of experts have made it possible to evaluate the advantages and drawbacks of each therapeutic method by defining its indications according to criteria of effectiveness such as duration of survival, quality of life of asymptomatic patients, gallbladder clearance, etc. We have tried to find out whether the introduction of medico-economic criteria in this pathology was likely to modify the various therapeutic methods available at present. We give here three examples. The first one is that of asymptomatic gallstones where the introduction of a cost/effectiveness ratio let to the conclusion that abstention is better than surgical treatment. The second example is a comparison of costs between cholecystectomy and medical treatment in high risk patients; the result was that surgery is preferable at the age of 50 years and medical treatment from 70 years onward. Finally, a comparison between surgery and lithotrity including the cost/effectiveness ratio concluded in favour of surgery. However, ethical, methodological and conceptual problems taking into account the value of human life, the difficulty to evaluate the quality of life and exterior incitations make it necessary to moderate the practical applications of these results. PMID- 1411180 TI - [Anti-cytoplasmic antibodies of polynucle or "ANCA". A new class of autoantibodies]. AB - The specific antigens to antineutrophil cytoplasmic antibodies (ANCA) and their relations with renal diseases begin to be well-known. In patients with systemic vasculitis, two major antigens have been recognized: proteinase 3 and myoloperoxydase. These enzymes are located in the azurophilic granules of neutrophils and migrate to the surface of these cells when they are activated. Other antigens, such as elastase, lactoferrin, CAP57 and cathepsin G, have been identified, but they are less commonly encountered. The presence of ANCA is particularly frequent in Wegener's granulomatosis, microscopic periarteritis, crescentic necrotizing glomerulonephrites without immunoglobulin deposits; it is less frequent in periarteritis nodosa and in Churg-Strauss' syndrome. ANCA can now be considered as markers of vasculitis; they are related to disease activity and can be used to evaluate the effectiveness of treatments. PMID- 1411181 TI - [Selective digestive tract decontamination (SDD) in intensive care patients. First European Consensus Conference in Intensive Care and Emergency Medicine]. PMID- 1411182 TI - [Puberty. Determining the criteria for normal development]. PMID- 1411183 TI - [Drug accidents of immunological origin. Physiopathology]. PMID- 1411184 TI - [Cutaneous ecto-parasitic diseases: pediculosis. Etiology, epidemiology, diagnosis, treatment]. PMID- 1411186 TI - [Burns. Etiology, physiopathology, diagnosis, principles of early treatment]. PMID- 1411185 TI - [Migraines. Diagnosis, principles of the treatment]. PMID- 1411187 TI - [Neurotic syndrome: conversion hysteria. Diagnosis, principles of the treatment]. PMID- 1411188 TI - [Lesions of ligaments and menisci of the knee. Physiopathology, diagnosis, development, principles of the treatment]. PMID- 1411189 TI - [A big task]. PMID- 1411190 TI - [3 cases of polyarthritis treated with recombinant alfa interferon]. AB - Bilateral symmetrical polyarthritis occurred in three patients (2 males and 1 female), with no previous history of inflammatory rheumatologic disease, given alpha-interferon for 1 1/2, 7, and 10 months as treatment of chronic non A-non B hepatitis, myelofibrosis, and thrombocytopenia with myeloproliferative disorder, respectively. Joint manifestations developed 1 1/2, 3, and 10 months after initiation of alpha-interferon in a dosage of 3.10(6) U three times a week, 4.5.10(6) U per day, and 8.10(6) U three times a week. Polyarthritis persisted following withdrawal of alpha-interferon in the two last patients of whom one had rheumatoid nodules and positive rheumatoid serology and the other had scleritis, exanthema, and negative rheumatoid serology. Erosive rheumatoid arthritis was diagnosed after 28 months and 12 months, respectively, in two patients who required systemic corticosteroids with antimalarials (1 case) or azathioprine after failure of methotrexate (one case). Follow-up in the third case (12 months) is too short to allow differentiation of systemic lupus erythematosus (ANA: 1/1500 H with anti-DNA antibodies 58 U/ml) and chronic autoimmune hepatitis. Reports of chronic inflammatory rheumatologic disease during alpha interferon therapy are exceedingly few in number. In the cases reported herein, alpha interferon may have either triggered or revealed the joint disease. To prevent occurrence of this complication, exclusion from alpha-interferon therapy of patients with autoantibodies or a positive history for clinical evidence of immune dysfunction may be considered. PMID- 1411191 TI - [Lumbar inter-apophyseal arthrosis and bone mineral content: prospective study versus controls with dual photonic absorptiometry and tomodensitometry]. AB - Dual photon absorptiometry (DPA) is a non invasive and repeatable technique to measure vertebral bone mineral content (BMC). This method can be altered, in frontal incidence, by superposition of abnormal calcifications as calcified aorta or interapophyseal arthrosis. The authors studied nineteen females with lumbar apophyseal arthrosis compared with twenty one controls matched by age. Bone densitometry was performed by Am-Ba DPA and monoenergetic computerised tomodensitometry (CT) from L2 to L4. Arthrosis was studied by standard X ray radiographs and CT. Our results showed that inter-apophyseal arthrosis does increase BMC determined by DPA, especially when expressed as linear BMC (g/cm). The body mass index [weight (kg)/size (m2)] also increased these measures by DPA. CT results were, at the opposite, not influenced by osteo-arthrosis nor body mass index. Detailed analysis of DPA pictures allowed to recognize most of patients with osteo-arthrosis and to correct their results by using adjacent vertebral measures (L1) or abandoning pictures of unusual aspect. The authors mentionned necessity to match populations for age and body mass index and to include L1 in routine vertebral bone mineral content determination. By this way they supposed that osteo-arthrosis may not alter lumbar BMC measured with DPA technique. PMID- 1411192 TI - [Aspects and role of spinal MRI in the assessment of solitary plasmacytoma and multiple myeloma. Apropos of 11 cases]. AB - Spinal MRI was performed in 9 multiple myeloma and 2 solitary plasmacytoma, using sagittal, T 1-weighted (TR: 350-550 ms/TE: 15-26 ms) and T 2-weighted (TR: 2,000 2,500 ms/TE: 60-120 ms) sequences, with additional gadolinium injection in 3 cases. MRI features were the following: 1) round, patchy lesions with low T 1 signal highlighted by gadolinium and bright T 2 signal were present in 10 of the 11 patients: all osteolytic lesions seen on plain X-rays corresponded to such lesions and biopsy performed in 4 cases showed massive marrow replacement by plasma cells. 2) overall marrow signal was dramatically decreased in 3 patients (2 of whom had a high tumoral mass). 3) extra-dural compression was present in 4 cases. 4) 25 vertebral compression fractures (10 of whom with a "benign" appearance) and focal fat deposition were seen. 5) postradiation treatment examination seemed predictive of the outcome in the 2 solitary plasmacytomas. MRI proved to be more sensitive than plain X-rays or bone scintigraphy. Number and size of focal tumor-like lesions did not correlate with the low marrow signal appearance. Both correlated poorly with overall tumoral mass but diffuse abnormalities were associated with rapidly fatal outcome in three cases. These features might reflect qualitative rather than quantitative patterns of the disease (nodular or diffuse macroscopic marrow replacement). These findings are in agreement with those of the few previous studies. MRI is valuable for spinal cord damage assessment. It appears less accurate in benign versus malignant vertebral compression fracture determination than it does in bone metastasis. Its prognostic value is still questionable. PMID- 1411193 TI - [Significance of inflammatory syndrome in the diagnosis of Horton's disease. Attempt at the application of Bayesian analysis]. AB - This study was designed to investigate the value of biologic evidence of inflammation for the diagnosis of giant cell arteritis. Experienced physicians were asked to evaluate five pairs of medical records based on real cases. In each pair, one case lacked biologic evidence of inflammation. This study offered the opportunity to explore the feasibility of a simplified Bayes model. A blind evaluation obtained by showing the paired case-reports with similar evidence of inflammation in both cases of each pair to 14 specialty physicians yielded a likelihood of diagnosis of +/- 20%. Analysis of the 46 responses to the study demonstrated, despite wide variations, a significantly greater likelihood of diagnosis in the cases with evidence of inflammation. Nevertheless, 17% to 36% of physicians--according to the case-report--ascribed virtually no importance to the ESR. Most of the physicians considered temporal artery biopsy was warranted when the likelihood of diagnosis was greater than 25%. Emergency corticosteroid therapy while awaiting the histologic results was approved by most responders when the likelihood of diagnosis was greater than 65%. The "pre-test" likelihood, calculated assuming that sensitivity and specificity of the ESR are 0.99 and 0.50, respectively, ranged from 0.89 to 0.98 for the case-reports with no evidence of inflammation and from 0.16 to 0.59 for the case-reports with evidence of inflammation In theory, the figures for the two types of case-report should not differ by more than 20%. Use of a low value for specificity (0.05) would improve the fit of values in cases without evidence of inflammation but would increase discrepancies in the other cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411194 TI - [Real effects of sport on the bone mass in women]. AB - What is the role of physical training in the prevention of osteoporosis? The authors tried to answer the question, comparing the positive and negative effects of exercise on women bone mass before and after the menopause and proposed a way of management of bone loss in amenorrheic women athletes. PMID- 1411195 TI - [Dermatopolymyositis induced by D-penicillamine in rheumatoid polyarthritis. Apropos of 1 case with review of the literature]. AB - Treatment of rheumatoid arthritis (RA) with D-penicillamine (DP) is associated with development of dermatopolymyositis (DPM) in 0.2 to 1.2% of cases. A case of DPM which developed after four years DP therapy in a 58-year-old female with RA is reported. The favorable outcome after discontinuation of DP and administration of corticosteroids and the absence of recurrence or malignant disease after 4 years 9 months follow-up demonstrated the causal relationship between DP therapy and development of DPM. An analysis of 34 previously published cases of DP induced DPM (DP/DPM) showed the following: development of DPM was not influenced by the dosage or duration of DP therapy; reported cases of DP/DPM were clinically identical with primary DPM but had a different outcome, with permanent recovery of DP/DPM occurring 1.5 to 6 months after withdrawal of DP; patients with DP/DPM had immune disorders, including antinuclear antibodies in 14 of 34 patients; the high prevalence of the B18, B35, DR4 haplotype in these patients denotes immunogenetic differences with primary DPM patients (B8-DR3) and DP-induced myasthenia (DR1). PMID- 1411196 TI - [Lumbosacral pain revealing intramural rectal abscess. Apropos of 2 cases]. AB - Intramural abscess of the rectum is an uncommon (7%) form of perianal abscess in which the suppuration moves upwards within the rectal wall. Diagnosis is usually readily established on the presence of prominent anorectal symptoms and on rectal examination findings. However, atypical cases occur occasionally. Two cases of intramural abscess with misleading presenting symptoms suggestive of rheumatologic disease are reported herein. Both patients had subacute lumbosacral pain suggestive of an inflammatory condition. In one patient, the correct diagnosis was established two years after onset of symptoms when the patient passed pus per rectum. In the other, endoscopic ultrasonography readily evidenced the abscess. Modern imaging techniques including endorectal ultrasonography, CT scan with enhancement and MRI are very helpful for the diagnosis of such difficult cases. Intramural rectal abscess should be added to the list of possible nonspinal visceral etiologies routinely looked for during the evaluation of patients with atypical lumbosacral pain. PMID- 1411197 TI - [Tibial hyperostosis and Propionibacterium acnes]. AB - In a 39-year-old patient with tibial productive osteitis, Propionibacterium acnes was identified in a surgical specimen of the bone lesion. Similar cases have been reported by others. The possibility that P. acnes may play in a pathogenic role in the SAPHO syndrome by causing inflammatory or infectious changes is discussed. PMID- 1411199 TI - [Osteoid osteoma of the olecranon]. PMID- 1411198 TI - [Brucella osteomyelitis of the upper end of the humerus: contribution of magnetic resonance imaging]. AB - The authors report a case of brucella osteomyelitis of the upper end of the humerus in a 77-year-old patient, presenting as a large swelling of the soft tissues of the shoulder, present for a year. The diagnosis was made by isolation of the organism and specific serology. The authors stress the value of magnetic resonance imaging, which provided confirmation of the diagnosis of osteomyelitis as well as an accurate topographic assessment. PMID- 1411201 TI - [Vertebral sarcoidosis with condensing pseudo-Paget's disease]. PMID- 1411200 TI - [Toxopachyosteosis with bilateral clavicular dysmorphism]. PMID- 1411202 TI - [Role of the intestine in the physiopathology of inflammatory rheumatism]. PMID- 1411203 TI - [Henry Bloch-Michel (1909-1992)]. PMID- 1411204 TI - [Inflammatory myalgic syndrome and muscular mitochondrial abnormalities: 4 cases]. AB - Histologic and biochemical anomalies of muscle mitochondria were identified in four patients with predominantly rhizomelic myalgia clinically suggestive of an inflammatory disease but inconsistent biologic evidence of inflammation. This clinical pattern was initially suggestive of atypical polymyalgia rheumatica and could not be ascribed to any other disease. To explain this combination of anomalies, several hypotheses can be put forward, including coincidence, aging, and nonspecific mitochondrial anomalies resulting from immunologic or inflammatory disease. The speculation that these patients have an autonomous syndrome cannot be outruled but should be considered with caution. A therapeutic trial with coenzyme Q is under way. PMID- 1411205 TI - [Infectious spondylodiscitis. Analysis of a series of 105 cases]. AB - Among 105 cases of infectious spondylitis diagnosed and treated from 1971 through 1990, 23 were due to tuberculosis (TS) and 82 to other causes (NTS). The annual number of cases of NTS rose over the study period, partly because of an increase in iatrogenic spondylitis, whereas the number of TS cases fell. In both groups, mean age of patients was higher than in earlier studies. The leading causative agents in NTS were staphylococci, followed by streptococci, then Escherichia coli. Diagnosis of spondylitis was dependent on the imaging techniques used; among available methods, the most reliable was magnetic resonance imaging which improved diagnostic performance by detecting early, specific changes. Except in patients with positive blood cultures and in TS patients with Koch bacilli recovered from other visceral foci, bacteriologic diagnosis rested on studies of samples taken from the spinal infection site. Half the subjects underwent discovertebral needle biopsy, with a success rate of 47.5%, a figure comparable with those reported in other studies. In 30% of patients, bacteriologic documentation of the infection was not obtained and diagnosis rested on a set of clinical, biological, and radiological criteria. PMID- 1411206 TI - [Rheumatoid metatarsals, original development of the first metatarsals]. AB - Weight-bearing roentgenograms of 308 feet of rheumatoid arthritis patients were analyzed. Several angles were determined, including the metatarsus primus adductus angle (between the first and second metatarsals, > or = 10 degrees) and the forefoot spread angle (between the first and fifth metatarsals, > or = 30 degrees). Pes planus was diagnosed when the internal arch angle was equal to or greater than 130 degrees. Tarsal arthritis was defined as the presence of joint space narrowing. Varus of the first metatarsal was correlated with tarsal arthritis and pes planus but not with duration of the disease. Forefoot spread was correlated with duration of the disease and erosive metatarsal disease but not with involvement of the midfoot. These data demonstrate that orthopedic treatment should be initiated as soon as involvement of the first metatarsal is detected and should be directed at the hindfoot, midfoot, and first metatarsal whose deformations occur concomitantly. PMID- 1411207 TI - [Value and limits of tomodensitometry applied to the diagnosis of sacroiliitis in young adults: study of 200 cases]. AB - Diagnosis of sacroiliitis may be difficult to establish in patients under 25 years of age since growth is not yet completed and joint damage is often still minor. A prospective study of 200 subjects with a median age of 22 years was carried out to compare the value of CT scan and conventional radiology. The study population included 32 healthy subjects and 168 consecutive patients with presumptive spondylarthropathy including 36 with bilateral sacroiliitis and 8 with unilateral sacroiliitis. Conventional roentgenograms and CT scans were performed in every patient. Blind reading of roentgenograms and CT scans was carried out by two pairs of observers with differing experience. CT scan provided no additional information when reading was done by experienced observers: rates of mistaken and doubtful results were similar with both investigations (10%); specificity of both tests was comparable (90%) but sensitivity was significantly greater for CT scan (91.2%) than for conventional roentgenograms (71.6%), reflecting improved detection of roentgenographically occult sacroiliitis. Less experienced observers obtained better results with CT scans, illustrating the ease of interpretation of CT scan images. Analysis of false-positive CT scans revealed that normal variations and, above all, features due to as yet uncompleted growth were the main sources of mistakes. These mistakes cancelled the advantage of increased sensitivity of CT scan studies and explained why CT scan failed to improve diagnosis. PMID- 1411208 TI - [Total prosthesis on a rheumatoid knee]. AB - Results of 81 total knee replacements in 67 patients with rheumatoid arthritis were studied. Mean follow-up was three years. Pain was the main reason for knee replacement surgery; knee mobility was well preserved prior to surgery. Failure occurred in four patients, as the result of infection, due in three instances to skin necrosis. Arthrodesis of the knee proved necessary in these patients. The fourth patient developed delayed hematogenous infection which was treated by a change of prosthesis. At follow-up, 82% of patients reported no pain and 18% moderate pain. Mean passive flexion was 113 degrees +/- 17 degrees. HSS score was 83.6 +/- 1.3 and all the patients except for the four with prosthesis failure stated that they were satisfied on very satisfied. Mechanical results were satisfactory, with a mean mechanical femur-tibial angle of 180.4 degrees. A circling line was visible at follow-up in 40% of operated knees but was partial in every case. No reoperations for prosthesis loosening were required. These data show that total knee replacement is the only reliable and radical treatment of rheumatoid arthritis of the knee and should be performed as soon as fixed flessum or axial deviation develops. PMID- 1411210 TI - [Lupus chorea revealing. Study in magnetic resonance imaging. Success of plasma exchanges after resistance to pulsed cortisone]. AB - Chorea as a manifestation of SLE is infrequent (1% of all cases of SLE). A new case is reported herein. The patient, a seventeen-year-old female, was admitted with a one-week history of choreic movements of the left half of the body and arthritis of both wrists. Biologic findings confirmed the diagnosis of SLE with presence of an antiprothrombinase circulating anticoagulant. Findings upon cerebral CT scan and magnetic resonance imaging were normal. Clinical symptoms worsened despite corticosteroids in a daily dosage of 1 mg/kg with three pulses of 800 mg methylprednisolone. High-dose neuroleptic therapy was given and three plasma exchanges were performed. A dramatic improvement in clinical symptoms and biological anomalies occurred and persisted during follow-up which now exceeds one year. The lack of MRI anomalies suggests that the pathogenesis of SLE associated chorea involves functional neurone activation by immune complexes; the dramatic effectiveness of plasma exchanges may obviate the need for using immunosuppressant agents in patients who fail to respond to corticosteroids. PMID- 1411209 TI - [Rheumatic manifestations associated with human immunodeficiency virus infection (HIV)]. AB - The number of subjects presenting articular manifestations associated with HIV infection is constantly on increase due to the growing number of seropositive patients. The pathophysiological mechanism of this association is still unknown. A recent review of the literature has shown that spondyloarthritis are the most frequently observed articular manifestations in HIV-positive patients. Septic arthritis are rare but severe. The immunodepression due to HIV-infection makes it difficult to use immunosuppressors and renders local therapeutics preferable. The articular manifestations may allow to discover seropositivity that has not been diagnosed before. These data strongly suggest to include serological examination for HIV in the etiological screening for every articular manifestation of unknown origin, even if the patient presents no risk factors. PMID- 1411212 TI - [Peripheral erosive arthritis in pustulosis palmoplantaris. Apropos of 3 cases]. AB - Three cases of pustulosis palmoplantaris with erosive arthritis are reported. There were two females (aged 53 and 59 years) and one male (aged 39 years). Skin lesions preceded joint lesions in every case (by 2 years, several weeks, and 1 year, respectively). Joints involved were one wrist in two patients and both hips in one patient. Inflammatory joint pain occurred concomitantly with an exacerbation of the skin disease. In two cases, an upper respiratory tract infection preceded the joint manifestations by a few days. Synovial fluid from affected joints was obtained in all three cases and found to be sterile. In the two patients who had histologic studies of skin lesion biopsy specimens, unilocular non-spongiform lesions suggestive of nonpsoriasic disease were found. Erythrocyte sedimentation rate and C-reactive protein levels were raised in every case. HLA groups were [A2, A19, B12, B27], [A2, A9, B12, B19, B27, Dr4, Dr6], and [A2, A19, B12, B13, Dr7, Dr8]. All three patients were given a nonsteroidal antiinflammatory agent. Despite this therapy, destruction of the wrist occurred in both females and bilateral hip destruction required bilateral total hip replacement in the male. The rapidity with which joint destruction occurred suggested infectious disease, especially due to a saprophytic organism. Virtually all previously reported pustulosis palmoplantaris patients with bone and joint manifestations had arthralgia or non-destructive arthritis in appendicular joints, whereas bone and joint destruction has been described in axial structures. PMID- 1411211 TI - [A case of benign chondroblastoma of the iliac wing treated by extensive exeresis and reconstruction with methylmethacrylate]. AB - Complete remission can be achieved by extensive surgical exeresis in patients with benign chondroblastoma of the iliac wing despite the reputation of these tumors for aggressive behavior. The case of a 28-year-old male treated with extensive surgery and acrylic cement reconstruction is reported. After seven years follow-up, the functional result is satisfactory and there is no evidence of local recurrence. Use of cement obviated the need for bone grafting. However, subsequent removal of the cement proved necessary because of skin intolerance. Data from a review of the literature confirmed that iliac chondroblastoma carries a poor prognosis, mainly because of the potential for mechanical complications. The cases of malignant transformation reported occurred after radiotherapy. In the authors' opinion, extensive surgical exeresis performed as early as possible is the treatment of choice. PMID- 1411213 TI - [Condensing myeloma. Apropos of 2 cases with bone histomorphometric study]. AB - Two cases of myeloma with roentgenographic evidence of bone sclerosis confirmed by iliac histomorphometric measurements are reported. In one patient, increased resorption, major depression of osteoblast activity, initial intense myelofibrosis, and myeloid deposits were found. The other patient had both increased resorption and increased osteoblast activity with clinical manifestations suggestive of POEMS syndrome. These two cases are compared with 116 cases previously published in the occidental medical literature and with five histomorphometric studies demonstrating increased bone trabecula volume (BTV). Conventional histologic studies suggest several mechanisms as possible explanations for the occurrence of bone sclerosis, including increased modeling unit activity, isolated osteoblast activation, metamorphic neoosteogenesis in myelofibrosis foci, and, in exceptional cases, inhibition of resorption due to increased production of calcitonin. The diversity of bone modeling patterns evidenced by the seven histomorphometric studies reviewed in this article is striking. Bone modeling patterns provide only a snapshot of bone modeling units and may vary over time in a given patient. Reported cases are too few to allow conclusions but emphasize the need for performing further histomorphometric investigations. PMID- 1411214 TI - [Megakaryoblastic transformation of myeloid splenomegaly with hypercalcemia and pseudomyelomatosis osteolysis]. PMID- 1411215 TI - [Misleading spontaneous lumbar intradural and extradural hematoma]. PMID- 1411216 TI - [Maurice Lepoivre (1910-1991)]. PMID- 1411217 TI - [Otologic manifestations of the pain dysfunction syndrome of the stomatognathic system]. AB - Phylogenesis, ontogenesis and anatomy explain the close relationship between temporo-mandibular joint and the middle ear and can therefore help understanding otologic symptoms such as: otalgia which often correspond to articular and muscular pain irradiation (coming from sterno-cleido-mastoid, lateral and medial pterygoid, deep layer of the masseter and temporal muscles); acouphens and ear block sensation that could be caused by a spasm extension of the manducatory (i.e. medial pterygoid) to levator and tympani tensors. These three muscles, which originate from the first branchial arch, have a proprioceptive sensitivity and share the same innervation. What is more tensor and levator veli exchange certain muscular fibers. Tensor tympani spasm can be held responsible both for a decrease or abolition of the Klockhoff's reflex, together with a decrease of the stapedian reflex, the latter due to tympani rigidity induced by a spasm of the tensor tympani. PMID- 1411219 TI - [The discal system of the temporo-mandibular junction]. AB - The discal apparatus represent the intra-articular part of the lateral pterygoid muscle tendon, which is differentiated in front of articular surfaces. It is involved in craniomandibular shock absorbing, joint proprioception, and also plays an important part in both condylar growth and morphogenesis. This is to emphasize the different roles of this apparatus, which should be religiously preserved, its lesions being, most of the time, irreversible and cause of TMJ disorders. PMID- 1411218 TI - [Occurrence of post-traumatic temporo-mandibular ankylosis. Trial of classification of anatomo-pathologic lesions]. AB - According to the authors, who have an 18-year experience, the treatment of temporomandibular ankylosis in children consists in the resection of the ankylosis block and of the corresponding neck of the condyle, along with the preservation of the capsule and articular disk and a dynamic blockade with the mouth open until the mandibular condyle is completely reconstructed. After witnessing the constitution of ankylosis in a child who was initially examined 3 weeks after the trauma, we were able to carry out a thorough clinicopathological examination of the areas of tissue characterizing incipient ankylosis, both in the condylar cartilage and in the underlying bone. The initial stage produces the progressive emergence of the bony surfaces, which then bear no cartilage. This is osteogenesis as well as cartilage resorption, as evidenced by the presence of neoformed Haversian canals at that level. This is a formal argument in favor of a systematic dynamic blockade with the mouth open in all cases of fresh condylar surface and the menisceal surface of the joint is the best way to prevent ankylosis or malunion. PMID- 1411220 TI - [Muscular insertions on the temporo-mandibular disk. Physiologic implications]. AB - The aim of this work was to identify the elements of an anatomical consensus about the description of the direct and indirect muscular insertions on the temporomandibular meniscus. A classical dissection was performed on two joints and completed with a histological study. Fourteen joints were studied, after deep freezing of fresh whole heads, with 3-millimeter thick macroscopic sections in the coronal, sagittal and axial planes and in a plane perpendicular to the axis of the condyle. The study of the specimens with a binocular magnifying glass was completed by oriented histological sections after fixation in 10% formaldehyde. The comparison of our findings with the studies published in the literature shows that the ideas are evolving towards an anatomical consensus about the reality of the direct and indirect insertion of the sole mandibular elevator muscles on the temporomandibular articular disk. The classical description of the dynamics of the meniscus must therefore be changed. PMID- 1411221 TI - [Complications of temporo-mandibular arthroscopy. Report of 100 arthroscopies]. AB - TMJ arthroscopy is a little invasive and of poor morbidity procedure of both investigation and treatment of temporomandibular pathology. A highly equipped operating room (double instrumentation) together with fine skill and proper knowledge of arthroscopic joint anatomy can easily prevent the rare complications described (articular, vascular, neurologic and otologic). PMID- 1411222 TI - [Reconstruction of the mouth floor with nasolabial flap after cancer resection. Report of 81 cases]. AB - The authors report functional results in a series of 81 patients with carcinoma of the floor of the mouth treated by surgical resection and reconstruction by nasolabial flap. The study confirms the literature concerning advantages and limits of such a flap. With regards to others techniques of reconstruction, nasolabial flap is still perfectly usefull in reconstruction of T2 T3 carcinomas of the floor of the mouth. PMID- 1411223 TI - [Dentascan in dental implantation]. AB - The software called dentascan utilizes the data acquired during a conventional CT examination to reconstruct accurate images with a 1/1 scale, both of sections taken at right angles to the axis of curvature of the bony relief of the maxillary or mandibular arch and of sections taken parallel to this axis. This means of investigation proves to be practical and useful for assessment before implantation. PMID- 1411224 TI - [Skin aplasia of the vertex. Report of a familial form]. AB - The authors report about a familial case of skin aplasia of the vertex cranii, of which they present a form that required emergent surgical repair with a favorable outcome. The investigation allowed tracing two relatives with minor forms expressed as alopecia of the vertex. Skin aplasia of the vertex cranii is an exceptional condition, which consists in the congenital absence of cutaneous, bony and/or dural tissue in the cranium. The various etiopathogenetic, clinical, diagnostic, evolutive and therapeutic aspects are reviewed. PMID- 1411225 TI - [Our experience with surgical treatment of posterior epistaxis. Report of 16 cases]. AB - Management of intractable posterior epistaxis remains a challenge to the otolaryngologist. When anterior and posterior packing techniques fail to control the hemorrhage, a surgical technique designed to interrupt the blood supply to the posterior parts of the nose is indicated. The common procedures employ ligation of the external carotid artery, of the maxillary artery and its terminal branch the sphenopalatine artery. Those procedures performed on 16 patients are clearly described and the indications for each one are established. Immediate control of bleeding was accomplished in 14 of 16 patients. Two patients had postoperatively recurrent but less severe epistaxis. PMID- 1411226 TI - [Microscopic innervation and vascularization of the tongue. General study]. AB - Our study deals with 23 prenatal human tongues, and a comparative study was carried out on one neonatal tongue and a few human and animal postnatal tongues. Sagittal and coronal sections were stained with various techniques. After the 7th week, the development of the nerves and their relationships with the neighboring structures can be observed. There are very few capillaries making up the superficial vascular network under the epithelium. The vessels whose walls are beginning to develop include the future red blood cells with their basophilic nuclei. During the whole process of evolution, there is a tight correlation between the collagen fibers and the neighboring structures. The innervation and vascularization--the latter with changes in the vascular walls--progressively increase. A short time before birth, the nerve fibers include their characteristic components, except for the Schmidt-Lantermann fissures. A considerable innervation advances towards the papillae, and anterior and posterior nerve networks enter the papillae, whose connective tissue includes groups of corpuscles on serial sections. PMID- 1411227 TI - [Decision strategy in orthognathic surgery. Part 2: The esthetic choice in orthognathic surgery--practical applications]. AB - Even if the functional factors are the most important in the decision, we have always to remember the need of our patient concerning aesthetic improvement. At this moment, the traditional approach based upon morphologic cephalometric analysis (which are frequently discordant) must be substituted by an aesthetic approach. The goal is to obtain a realistic 3D-imaging of the face as it will be after surgery. But it cannot really be achieved yet and we are obliged to work on lateral X-ray cephalograms. The most important at this stage of the decision is not to make a static aesthetic evaluation. It is on the contrary to perform a prospective simulation of the new profile line, as accurate as possible, based upon statistical correlations between soft- and hard-tissues changes. Even if there are some technical problems, even if the results are not currently good enough, the aesthetic prospective analysis allows validation or modulation of the initial functional surgical indication. We can compare for instance the aesthetic results of different amounts of displacements in bimaxillary surgery. Meanwhile, it is sure that the result depends also on the precision of the surgical procedure and on the good functional re-equilibration which is essential for the stability. PMID- 1411228 TI - [Post-traumatic enophthalmos. Pathogenic, diagnostic and therapeutic approaches]. AB - Post-traumatic enophthalmos has a complex pathogenesis, resulting from injuries to the bony walls of the orbit or to the intraorbital contents. Computed tomography allows specifying this pathogenesis by locating displaced bone, fat leakage or muscle incarceration, as well as calculating the volumes of the orbit and of the soft tissues. This assessment guides surgery (most often bone grafts), but correction remains limited by scar retraction, especially around the orbit. The prognosis of enophthalmos mainly depends on a general initial treatment after the trauma. PMID- 1411229 TI - [Enophthalmos of the enucleated eye]. AB - Even when it is corrected by an ocular prosthesis, enucleation often causes enophthalmos. After studying the integrality of the walls of the orbits with CT, the presence and position of the intraorbital implant must be controlled and the enophthalmos treated by compensating for the residual volume loss of the orbital content (bone or biomaterials) and, sometimes, filling up the upper palpebral space (dermal graft, galea flaps or biomaterials). The retraction of palpebral scars limits the possibilities of correction. PMID- 1411230 TI - [Cutaneous melanoma of the cervicofacial region. Personal experiences]. AB - The malignant melanomas are expansive tumors of neoplastic melanocytes. In the present study, five cases of patients are reported which have been hospitalized in E.N.T. department of our hospital during the last four years with skin melanomas of the head and neck. We note our opinions on diagnosis and treatment of these malignant tumors. PMID- 1411231 TI - [Inverted papilloma of the nose. Apropos of a case associating polyps and an inverted papilloma of the nose]. AB - In this article is presented a case report of a 59 years old woman with a medical history of recurrent nasal polyps (from 20 years ago). This woman presented an inverted papilloma in the middle meatus of the lateral wall of the nasal cavity simultaneously with the nasal polyps, and she was faced with surgical intranasal removal. The patient, two years later, presented again nasal polyps, but without any indication of the recurrence of the inverted papilloma. It is noticed the value of the local surgical removal of the inverted papilloma in patients who do not present extensive tumors. PMID- 1411232 TI - [Orofacial dyskinesia. A current pathology]. AB - Bucco-facial dyskinesia is particularly frequent in aged persons, for whom the condition is a definite handicap because of its social and, sometimes, functional impact. The etiology of these abnormal movements is variable. On one hand, many treatments can be incriminated, especially neuroleptics, and on the other hand, there also are frequent spontaneous dyskinesias, movements for which the risk factors are described. The physiopathology remains open to discussion and research, but we already know that the regulation of the nigro-striated pathway plays a role in it, as well, maybe, as toxic (free radicals) and immunological factors. Various therapies are described, but the outcome for such dyskinesias is often unfavorable, at least in elderly subjects, hence the merits of prevention. The latter is based on the prescription of as few neuroleptic drugs as possible, on the use of possibly protective substances, and finally on the suppression on the triggering elements that some local factors may form. PMID- 1411233 TI - Inadvertent intracranial placement of a Foley catheter. A rare iatrogenic complication of severe frontomaxillary trauma. AB - Severe comminuted fractures of the facial bones involving the cranial base are often accompanied by heavy bleeding into the nasopharynx. This presents considerable problems in primary care both for the anesthesiologist and the surgeon. Such bleeding can be controlled by Bellocq tamponade or using a Foley inflatable catheter. Skull base fractures may involve the risk of the catheter inadvertently penetrating into the brain. The authors describe a case in which a misguided Foley catheter, which was blindly inserted through the nose in an attempt to tampon the nasopharynx, resulted in fatal cerebral damage. PMID- 1411234 TI - [Biopsy of the salivary glands. The importance and technic of biopsy of the sublingual gland on its anterio-lateral side]. AB - A new method of taking a sublingual gland sample is suggested by the authors in the fore pole. They emphasize on this straightforward operating act and on the amount of tissue removed. The aim of the removal could be etiologic within the framework of the Gougerot-Sjogren's syndrome, diagnostic in the sarcoidosis and rheumatoid arthritis, prognostic in the graft versus host disease. PMID- 1411235 TI - [Adenomatoid odontogenic tumor]. AB - Adenomatoid odontogenic tumor is observed most frequently in male patients aged between 10 and 20 years. Occurring usually in the anterior part of the upper jaw, its discovery is often fortuitous during routine radiological examinations, which show a well defined clear zone 1 to 3 cm in diameter. Treatment by curettage results in healing by secondary bone cicatrization. A case is reported and epidemiological, clinical, diagnostic, therapeutic and prognostic features reviewed. PMID- 1411236 TI - [The use of cryotherapy in oral pathology. Our experience in 36 cases]. AB - Cryotherapy is a simple to use, weakly invasive technique provoking only moderate complications in the treatment of certain mucosal lesions of the buccal cavity. Indications of choice for this type of treatment are angioma and papilloma. Long term follow up of patients treated for reactive keratosis or epithelioma in situ is at present insufficient to establish precise indications. PMID- 1411237 TI - [The brevity of the acquisition period of phonemes. Arguments for the early treatment of maxillo-palatal clefts]. AB - Very early, the new-born no more listen the phonemes which are not used around him. In the same way, he does not listen the phonemes impossible to pronounce by himself, because he is not concerned. He does not engrave then. Consequently, we must give him, quickly, complete anatomical means of pronunciation, and train him by early intensive imitation-interchange mechanism. For those two reasons, we propose to complete immediately the early surgical reparation of the soft palate by a thin obturating plate and by an early orthophonic parental guidance. PMID- 1411238 TI - Upper gastrointestinal bleeding as a complication in end stage renal disease patients. AB - The commonest pathological findings in the upper gastrointestinal tract have been verified by studying 320 autopsies as related to chronic renal failure through the 20-year span. In our series of 99 patients having been hospitalized within the period of 1989 to 1990, lesions of upper gastrointestinal tract were summarized that might be responsible for bleeding in the course of the dialysis and after renal transplantation. In accordance with literature sources, the investigated group showed gastric and duodenal mucosal lesions to be the most frequent sources of hemorrhages. For both the early diagnosis and therapy all patients have to be examined prior to the initiation of a regular maintenance dialysis. Gastroscopy is also indicated in all patients without any exception. Subsequent conservative treatment should be performed in an intensive and accurate way. While unsuccessful, the surgery is indicated. Authors referred to indicatory criteria based on surgical management of gastroduodenal ulcer. Both the early diagnosis and indication to surgery were stated to be of crucial importance for patient's destiny when the conservative treatment has failed. The present study should contribute to a closer collaboration of nephrologists, gastroenterologists and surgeons in order to prevent such serious complications that are represented by gastrointestinal bleeding in patients with chronic renal failure. PMID- 1411239 TI - The changing pattern in peptic ulcer surgery. AB - The authors analyse the methods of treatment for the peptic ulcer disease (PUD) in two 5-year periods (group A 1979-1983, group B 1985-1989). From these groups patients with perforated gastroduodenal ulcer were excluded. In the first period 206 operations were carried out using nearly exclusively classical partial gastrectomies of both types (94 per cent). The second period involves 94 operations, where the most frequent type of operations was the proximal gastric vagotomy (40.4 per cent), and vagotomy with anthrectomy in the Roux-en-Y modification (26.6 per cent). The number of operations for a complicated PUD has increased from 43.2 per cent to 53.2 per cent, the ratio between the duodenal and gastric ulcer has changed from 3:1 to 2:1. The mortality was 5.3 and 4.7 per cent respectively, the morbidity 14.5 and 13.8 per cent respectively. The authors confirmed their accordance with the world-wide trend of diminution of the proportion of surgically treated PUD and a shift in the pattern of surgical methods towards the non-resective and more physiological procedures. PMID- 1411241 TI - Complicated duodenal ulcer, vagotomy or distal resection--own experience. AB - An analysis of clinical material through 10-year-period (1980-1989) is presented. There were 708 gastric operations performed for gastroduodenal ulcer disease. Most frequently distal gastric resections (585) were used, 233 in B. I. and 352 in B II. modification. Selective proximal vagotomy (SPV) was less frequently used (only 116 cases). Authors think there is no reason for a general use of SPV for each form of duodenal ulcer because of very serious competition with the H2 blockers. A different individual proved choice of the method as well as an appropriate subtle operating technique is considered to be essential. PMID- 1411240 TI - Surgical treatment of cardiospasm and megaoesophagus. AB - Long-term results of operative treatment of cardiospasm and megaoesophagus in 111 patients are presented. There were 67 women and 44 men treated, age 4 to 65. The authors have for several years used their own, in this Department developed method of operation for cardiospasm, which joins Heller's operation with the reconstruction of the cardia to prevent reflux. In very advanced stages of the disease as megaoesophagus they use an original surgical procedure, which consists in connecting the thoracic segment of the oesophagus with the prepyloric part of the stomach by means of a pedicle jejunal graft. Clinical follow-up supported by x-ray examination and endoscopy has shown very good results of such treatment. PMID- 1411242 TI - Pathogenesis of carcinoma in operated stomach--an animal model. AB - An experimental study on rats was performed to observe pathogenetic factors causing cancerogenesis in operated stomach. In sets I and II without exogenous carcinogen exposition 450 rats were operated upon by a different methods. In groups I it was B II gastrectomy, B II with Braun's anastomosis, B II in Roux en Y modification, B I and B I with jejunal interposition. In group II non-resective methods were tested: gastroenterostomy, gastroenterostomy with Braun's anastomosis, gastroenterostomy in Roux en Y modification, and vagotomy with pyloroplasty. In the group III 147 rats with different gastric operations were submitted to oral nitrate and nitrate with ascorbic acid exposition. The results confirmed significant pathogenetic influence of enterogastric reflux on cancerogenesis in the operated stomach. Ascorbic acid added to the exogenous cancerogen leads to a suppression of development of gastric cancer in rats. PMID- 1411243 TI - [Fibroplastic dust and cardio-respiratory functions]. AB - Repeated measurements of dust concentrations and work loads were made at the workplaces in iron foundries (interval 10 years) and processing of asbestos (dusts 27 years and work load 8 years). The work load was mild to moderate, rarely heavy (energy output 2.0 to 5.7 MJ in the shift) with a mean heart rate 94 106. The incidence of occupational diseases was stabilized in the foundries, increased in the asset processing plants (mostly lung cancer). Two thirds of the workers were smokers, in spite of that the workers in the foundries had their mean flow-volume curve almost identical with the standards. Their age conditioned diminution was faster especially for FEF50 and 25 and accompanied with a bigger rise of FRC and RV. Exercise testing demonstrated the same fitness as in normal population (2.7 +/- 0.7 l/min). As far as asbestos processing is concerned, a diminution of dust concentrations below the limits was found. Despite of this, an increase in lung cancer incidence was observed probably as a consequence of high dust concentrations in the past and smoking habits (2/3 of workers). The flow volume curves were obviously smaller than the normals. With the rising of exposure to asbestos and with the advancing age (more close correlation), the deterioration of respiratory parameters (measured during 6-7 years) was two times faster. The correlations were more close for women then for men. In the man group, this deterioration was greater in the last measurements. The results of ergometer testing up to anaerobic threshold were identical with those found in normal population. PMID- 1411244 TI - On the relationship between theoretical presumptions asbestos genotoxicity and the practical monitoring of exposed workers. AB - From the genotoxic viewpoint, there exists a sufficient evidence for asbestos carcinogenicity to human population and animals. Asbestos is a solid cancer promoter (cocarcinogen) of non-mutagenic character having epigenetic effects (15, 16). No data have been published on its mutagenic activity in "in vivo" conditions in man. The only results are those of our pilot study carried out in the period of 1981-1983, which cast doubts on the official view of non-mutagenic character of asbestos--at least under occupational conditions of its processing (34, 36, 37). The study presented here represents ten years' efforts made in the biological (cytogenetic) monitoring of persons occupationally exposed to asbestos in a factory for its processing (occupational risk). Simultaneously, a preliminary answer is given to the question whether the Osinek factory (situated in a housing area) is or is not dangerous for inhabitants of the town of Kostelec nad Orlici, namely for their genetic apparatus (environmental risk). Using the method of chromosome aberrations analysis in peripheral blood lymphocytes, a total of 431 subjects (245 males and 186 females) were examined in the period of 1981 to 1988. Of these, 111 persons were from control workplaces (from Osinek or- starting from 1984--from other plants in Kostelec nad Orlici; in addition to that 14 pensioners without any occupational exposure were examined). The average age of workers exposed to asbestos risk was 42.7 years, in the controls it was 43.9 years, in pensioners exposed to asbestos earlier 63.5 years and in those never exposed to asbestos 66.5 years. The average number of years spent at Osinek factory amounted to 21.5 years. About one third of employees were found to suffer from allergies (first of all those of air passages) and one sixth from chronic ailments of the upper air passages (Staphylococcus aureus, Haemophilus influenzae and Streptococcus beta-haemolyticus were diagnosed most frequently). A third part of workers from high-risk workshops are smokers, only a fourth of the controls. About 40% of workers regularly consume alcoholic drinks. The average morbidity rate at Osinek in 1981 to 1988 was 6.3% (in workers as high as 9%), which is about 2% higher as compared with mean values obtained in the district of Rychnov nad Kneznou and East-Bohemian region. Within the nine-year period (1981-1989), 21 occupational diseases were diagnosed, while in the previous 24 years there were 24 cases of an occupational disease. Earlier they were mainly asbestoses (87%), in the last period mainly cancer diseases coinciding with asbestosis (81%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1411245 TI - Scleroplasty in progressive myopia--selection of materials. AB - Scleroplastic surgery is known to encounter the pathogenetical agent when the progressive myopia develops. In the first part, the implemented surgical approaches as well as up-to-date surgical techniques are presented. The experimental part is reserved for the selection of material which is necessary to perform scleroplasties. Both the allogenic and xenogenic grafts have been studied for histocompatibility on 20 rabbits. Following materials were used: 2 types of collagenic sponge, native and deproteinated human sclera, modified dura mater as well as both the native and devitalized sclera from rabbits. The best results were obtained with allogenic sclera, deproteinated xenogenic sclera and collagenic sponge. The application of other materials is discussed. PMID- 1411246 TI - Communication with patients as a problem in undergraduate medical education. AB - The work is based on the following concepts: communication with patients ceases being a matter of experience learning only (the trial and error method) and should become a part of systematic training; it should not be included only into continuous education of graduated physicians but must be gradually introduced into undergraduate education as well; it is not an optional activity which may but may not be performed by physicians, but it is a specific component of their clinical competence. Today attempts to instruct medical students in communication with patients and their relatives are being made at many medical schools all over the world. Reports on such instruction are, however, scattered in various journals or in internal publications published by universities, faculties and clinics. Thus they are not available very easily. If there exist some survey works, they are mostly conceived on the national level. The objective of the study presented here is to show a comparatively comprehensive survey dealing with the medical student instruction on the international level, analyze trends in development and identify problems that have not been solved so far. The work consists of five chapters. The first one gives a short survey of current concepts in communication with patients reaching beyond the traditional training in taking medical history. Among others, the following factors are included here: explanation of both diagnostical and therapeutical methods to the patient, informing the patient about results obtained from the examination, telling him or her general conclusions and recommendations, informing patients of social associations of the disease, developing in the patients those attitudes which support their cooperation with physicians and the patient's will to live, ability to treat serious and terminal patients properly, ability to treat patients' relatives and communicate with other members of a medical team. The second chapter shows current attempts to train the medical student-patient communication in Czechoslovakia, especially at Charles University. Third chapter describes how medical students in the former USSR were instructed, especially at medical schools in Moscow. This kind of information is still difficult to be had for people from abroad. The fourth chapter is the most important. Current attempts to train medical students in communication with patients in Europe, North and South America, Asia, Africa and Australia are described there. Reference frames in which the instruction takes place (medical, educational, psychological frames) are studied.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1411247 TI - Increased breathing gas density enhances cardiac workload. AB - The effect of increased breathing gas density on the left ventricular pressure (LVP), cardiac contractility (dP/dt), heart rate (HR), intrapleural pressure (P(ip)) and respiratory frequency (RF) was evaluated in pentobarbital anaesthetized rats (n = 8) and cats (n = 6). Catheters were placed in the left cardiac ventricle via the right carotid artery to measure the LVP, in the oesophagus for indirect measurements of P(ip) and RF, and into the aorta from the right femoral artery for arterial pressure measurements. The RF fell significantly within the first 30 s and had reached a stable value 2 min after gas shift in both rats and cats. Concomitant with the RF fall, the depth of inspiration and intrapleural pressure differences in both rats and cats increased. The acid-base balance remained at control levels in both animal groups. LVP and dP/dt started to increase during the first half-minute, and reached their maximum values 2-5 min after the introduction of normoxic sulphur hexafluoride. A linear relationship between the enhanced dP/dt and the P(ip) increase was found. The HR remained unchanged in both cats and rats. These findings indicate that the breathing gas density might influence the cardiac contractility found during hyperbaric exposure, and that a gas density of five times that of air at 1 bar does not influence the diffusion of O2 and CO2 in the lung. The O2 consumption of the heart in cats and rats was calculated to rise by 25% and 30% respectively in the dense breathing gas atmosphere. PMID- 1411248 TI - Response of diastolic blood pressure to long-term sodium restriction is posture related. AB - Eighty-five subjects, aged 31-55 years, suffering from uncomplicated essential hypertension and receiving no regular medication were randomized to sodium restriction and control groups. Systolic (SBP) and diastolic (DBP) blood pressure were measured during an orthostatic test at baseline and after 6 months sodium restriction. The mean daily sodium excretion of 43 treated subjects decreased from 193 +/- 91 mmol to 95 +/- 70 mmol (p less than 0.001). Treated patients were divided on the basis of their mean overall out-patient clinic (OC) DBP decrease in the sitting position during the 6 months (monthly measurements) into sodium sensitive (DBP decrease greater than 10 mmHg, n = 17), indeterminate (DBP decrease 5-10 mmHg, n = 18) and sodium-resistant (DBP decrease less than 5 mmHg, n = 8) subgroups. At 6 months the level of DBP in the supine position was lower than at baseline in both sensitive and resistant subgroups, whereas in the standing position a lower DBP than at baseline was seen only in the sodium sensitive subgroup. The magnitude of the subsequent OC DBP decrease was significantly associated with a high baseline seated OC DBP (p less than 0.001) and a high, for baseline OC DBP adjusted orthostatic DBP increase (p = 0.014). Our data suggest that posture should be included in the concept of sodium sensitivity and that an orthostatic test is useful in the prediction of seated and standing DBP decrease produced by moderate, long-term sodium restriction. PMID- 1411249 TI - A microtitre assay system for glucocorticoid receptors: decreased receptor concentration in myocardial infarction. AB - A major difficulty in determination of glucocorticoid receptor sites is the very complicated assay procedure. Therefore, we describe a microtitre assay system for glucocorticoid receptors which is a whole-cell competitive binding radioassay using [3H]-dexamethasone as radioligand. This modification of a previously described protocol simplifies and reduces laboratory work and allows assay reproducibility to be controlled more reliably. Thus enabled to perform the test on multiple blood samples in parallel, we investigated cardiac infarction patients over a 12-day period to test if glucocorticoid receptor binding is altered in this 'stressful' disease. On the first day of the disease, glucocorticoid receptor capacity was significantly decreased without alteration of the receptor-ligand affinity, whereas on days 4 and 12 the number of receptor sites was normal again. This result fits well into the general observation of stress-induced down-regulation of immune responses. PMID- 1411250 TI - Both the polysaccharide and lipid A parts of endotoxins are needed for the inhibitory effects of endotoxins on cellular LDL uptake. AB - We previously reported that endotoxins inhibit low-density lipoprotein (LDL) uptake and degradation in Hep G2 cells. In the present study, we tried to elucidate which part(s) of the endotoxin molecules contribute(s) to the inhibitory effect of endotoxins on LDL uptake and degradation. The results show that the endotoxin isolated from Salmonella minnesota Re595 (Re mutant), which lacks polysaccharide, had no effect on the uptake and degradation of 125I labelled LDL in Hep G2 cells. This mutant form also decreased the inhibitory effects of endotoxins which have complete polysaccharides on cellular LDL uptake and degradation. However, the polysaccharide part of endotoxins by itself had no effect on LDL catabolism by the cells. This suggests that both the polysaccharide and the lipid A parts of endotoxins are needed for the inhibitory effects of endotoxins on LDL uptake and degradation. PMID- 1411251 TI - Enhanced urinary excretion of albumin in congestive heart failure: effect of ACE inhibition. AB - Urinary excretion of albumin and beta 2-microglobulin were measured in 13 patients with congestive heart failure, NYHA class II-IV, before and after captopril treatment for 4 weeks, and in 13 healthy control subjects. The urinary excretion of albumin was enhanced in heart failure patients compared to control subjects (12.0 micrograms min-1 vs 2.8 micrograms min-1; medians, p less than 0.01), whereas beta 2-microglobulin excretion was normal. No significant change in urinary excretion of albumin was observed after captopril. Using Spearmann's test the urinary excretion of albumin was correlated to the NYHA class (Px = 0.681, p less than 0.05, plasma renin (Px = 0.886, p less than 0.01) and plasma angiotensin II (Px = 0.5840, p less than 0.05). Correlations with atrial natriuretic peptide (rho = 0.412, p = 0.153) and aldosterone (Px = 0.487, p = 0.106) did not reach significance. By multiple linear regression analysis only plasma renin activity was correlated to albumin excretion. In conclusion, patients with congestive heart failure had an increased urinary excretion of albumin. It is suggested that the enhanced transglomerular passage of albumin in congestive heart failure is partly due to an increased intra-renal angiotensin II generation, but elevated plasma level of atrial natriuretic peptide and increased renal venous pressure may also be important pathogenetic factors. PMID- 1411252 TI - CA 125 serum levels in patients with non-neoplastic liver diseases. A clinical and laboratory study. AB - CA 125 is a tumour marker usually used in the monitoring of ovarian carcinoma patients. This study was performed to evaluate the behaviour of CA 125 in 159 patients with benign diffuse hepatic diseases who underwent thorough clinical and laboratory evaluation. Abnormal serum levels of CA 125 were found in 40.3% of the 159 patients, 70.6% of the 85 cirrhotics and 5.4% of the 74 non-cirrhotics. There was a correlation between CA 125 and numerous biochemical parameters characteristic of liver diseases, the liver failure tests being the most relevant. Ascites was a determining factor of serum CA 125 levels (98.4% of the ascites patients and only 4.1% of the non-ascitic patients had abnormal levels), and CA 125 had excellent sensitivity, specificity, efficiency, predictive values and likelihood ratios to detect ascites. In the absence of ascites, liver dysfunction played a small but significant role in the increase of CA 125. In liver disease patients with ascites the threshold required to obtain only 10% of abnormal values was more than 50-fold the basal level. These findings invalidate CA 125 as a tumour marker in these patients. PMID- 1411253 TI - Alteration of erythrocyte glutathione, cysteine and glutathione synthetase in alcoholic and non-alcoholic cirrhosis. AB - Glutathione (GSH) and cysteine were determined in the plasma and the erythrocytes of alcoholic and non-alcoholic cirrhotics as fluorescent monobromobimane derivatives by high-performance liquid chromatography (HPLC). Cirrhotic patients displayed a significant decrease of plasma GSH, as well as of plasma cysteine, that was related to the degree of liver disease but not to the nutritional conditions. On the contrary, erythrocyte cysteine was found to increase significantly in all cirrhotics, particularly in alcoholics, regardless of the severity of disease. In an attempt to find a possible explanation of these alterations, the GSH synthesizing enzymes, gamma-glutamylcysteine synthetase (GC s) and GSH synthetase (GSH-s) activities were determined in the erythrocytes. GSH s activity was significantly lower in cirrhotic patients, whereas GC-s activity did not differ in the three groups. PMID- 1411254 TI - Long-term supplementation with n-3 fatty acids, I: Effect on blood lipids, haemostasis and blood pressure. AB - The effect of dietary supplementation with 4 g of n-3 polyunsaturated fatty acids (PUFA) daily for 9 months on blood pressure, plasma lipids and lipoproteins, platelet function, coagulation and fibrinolysis was studied in 24 healthy volunteers. Each variable was determined before, after 6 weeks and 9 months of supplementation with n-3 PUFA, and 3 months after the supplementation period had ended. Systolic and diastolic blood pressure declined after intake of n-3 PUFAs. Plasma triglycerides were reduced, and there was a trend towards an increase in HDL-cholesterol after 9 months of supplementation, while total cholesterol, LDL cholesterol and apolipoproteins A1 and B were unaltered. The bleeding time was increased, and plasma levels of von Willebrand factor decreased after 9 months supplementation with n-3 PUFA. Fibrinogen levels increased, while fibrinolysis was reduced after 9 months supplementation with n-3 PUFA. Overall, no clear benefit on lipid pattern and haemostasis was achieved with respect to development of coronary heart disease. PMID- 1411256 TI - Thyroid function tests: performance and limitations of current methodologies. PMID- 1411255 TI - Long-term supplementation with n-3 fatty acids, II: Effect on neutrophil and monocyte chemotaxis. AB - The effect of a daily supplement with 4 g of n-3 polyunsaturated fatty acids (PUFA) for 9 months to 24 healthy volunteers on neutrophil and monocyte chemotaxis was studied using the under-agarose technique. Autologous serum and n formyl-methionyl-leucyl-phenylalanine were used as chemoattractants. The effect after 9 months of supplementation with n-3 PUFA was also compared to results after short-term supplementation with n-3 PUFA for 6 weeks. Monocyte chemotaxis was reduced after 9 months of supplementation with n-3 PUFA to the same extent as after 6 weeks supplement. Neutrophil-directed migration towards chemoattractants was reduced after 9 months on fish oil, and this decrease was significantly greater than the decrease obtained after 6 weeks of supplementation. The spontaneous migration of neutrophils was significantly attenuated after 9 months compared to baseline and to 6 weeks. These findings lend support to a role for n 3 PUFA in the management of chronic inflammatory and atherosclerotic vascular diseases. PMID- 1411257 TI - Radio-immunoassay of atrial natriuretic peptide (ANP) and characterization of ANP immunoreactivity in human plasma and atrial tissue. AB - A sensitive radio-immunoassay (RIA) was developed to determine the occurrence of atrial natriuretic peptide (ANP) in plasma and atrial extracts from patients undergoing open heart surgery. The immunoreactive ANP (irANP) was characterized by high-pressure liquid chromatography coupled with RIA. The plasma irANP response to releasing stimuli during the operation was determined in simultaneously sampled venous and arterial blood, in order to evaluate any differences. The antiserum recognized the intact ring-structure of alpha-humanANP (alpha-hANP) and its propeptide gamma-hANP, as well as beta-hANP, an anti parallel dimer of alpha-hANP. Less bioactive N-or C-terminal fragments of alpha hANP, or an N-terminal fragment of the propeptide, gamma-hANP 1-67, did not cross react with the antiserum. Sep Pak C18-extraction of plasma resulted in an 80% recovery of synthetic alpha-hANP. The assay had a sensitivity of 1.9 pmol l-1, well below the venous plasma concentrations of irANP found in healthy volunteers (7.4 +/- 1.3 pmol l-1, mean +/- SEM, n = 19), and the local standard was identical to an international standard of alpha-hANP. In atrial extracts three major peaks of irANP were identified as alpha-, beta- and gamma-hANP, with gamma hANP as the most abundant form. In plasma alpha-hANP dominated, but in two cases high plasma levels of beta-hANP were seen, reflecting the high atrial content in these patients. In peripheral arterial blood, irANP was on an average 56% +/- 20% (p less than 0.01, n = 18) higher than in venous blood; this was associated with more distinct arterial irANP responses to releasing stimuli during the operation. PMID- 1411258 TI - Calcium clamp technique: suppression of serum intact PTH by induced hypercalcaemia in normal man and primary hyperparathyroidism. AB - The aim of the study was to investigate the interrelation between induced hypercalcaemia and serum intact parathyroid hormone (S-PTH(1-84)) in normal man and in patients with primary hyperparathyroidism (PHPT) by measuring blood ionized calcium (B-Ca++) and S-PTH(1-84) before and during a controlled calcium infusion. Guided by frequent measurements of B-Ca++, we adjusted the calcium infusion rate continuously, thereby keeping B-Ca++ in a steady state at a pre determined level approximately 0.25 mmol l-1 above baseline values. This calcium clamp technique (CCT) applied to 14 normal volunteers for 120 min established a standardized reference for parathyroid suppression and the renal physiological PTH response. The reproducibility of the method and the results obtained by the CCT were satisfactorily assessed in six of the 14 normal subjects. In normal subjects B-Ca++ was raised from 1.25 +/- 0.3 mmol l-1 (mean +/- SD) to 1.49 +/- 0.02 mmol l-1 suppressing S-PTH(1-84) to 264 +/- 9.9% of pre-infusion levels. We applied the CCT to 10 patients with PHPT for 120 min raising B-Ca++ from 1.41 +/- 0.09 mmol l-1 to 1.69 +/- 0.08 mmol l-1, thereby suppressing S-PTH(1-84) to 47.9 +/- 16.3% of pre-infusion levels. The renal handling of calcium and phosphate during CCT demonstrates the biological effects of suppressed activity of PTH on the renal tubules showing increments in the maximal tubular phosphate reabsorption in relation to the glomerular filtration rate (TmP/GFR) and decreased tubular reabsorption fraction of calcium. The described CCT is a safe and reliable dynamic test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411259 TI - Cardiac systolic time intervals and thyroid hormone levels during treatment of hypothyroidism. AB - This study was undertaken to compare results of modern serum thyroid hormone assays with cardiac systolic time intervals (STI) during thyroxine treatment in hypothyroid patients. The patients were assessed clinically (Billewicz index) and the STI and serum thyrotropin (TSH), total and free thyroxine (T4) and total and free triiodothyronine (T3) were determined in 16 hypothyroid women (Group I) treated with 50 micrograms increments of thyroxine, and in 13 women who had a history of thyroid carcinoma and high-dose thyroxine replacement therapy and had elevated thyroid hormone concentrations (Group II). The STI of 24 matched healthy female controls were used for reference of STI. The pre-ejection period (PEP) index and the PEP/LVET ratio (left ventricular ejection period) were greater in untreated overtly and mildly hypothyroid patients (p less than 0.05) than in the controls. During stable thyroxine therapy [mean daily dosage for Group I 137.5 (7.3) micrograms and for Group II 220 (61) micrograms] the PEP correlated with serum free T4 (FT4), as measured by a two-step method (SpectriaR) (r = -0.55, p less than 0.01, n = 29) and total T4 (r = -0.51, p less than 0.05, n = 29), but not with TSH, T3, FT3 or FT4 measured by an analogue method Amerlex-M(R). The TRH test was not valuable in follow-up because of the strong correlation between basal TSH and stimulated TSH values (r = 0.95). In conclusion, STI are useful for assessment of the thyroid state in untreated hypothyroid patients. Serum TSH becomes normal in the same time as STI and is the best for follow-up. If serum TSH is low and the patient is on stable thyroxine therapy, we recommend serum FT4 for monitoring thyroxine replacement. Two-step FT4 assays had the best correlation with STI, which has significance in patients with non-thyroidal illness. PMID- 1411260 TI - Levels of calprotectin (leukocyte L1 protein) during apheresis. AB - The plasma concentration of calprotectin was measured before, during and after apheresis in patients with Guillain-Barre Syndrome (GBS), Waldenstrom's syndrome or hypercholesterolaemia and in healthy donors of platelets. Increased calprotectin levels were found after plasma exchange in the Waldenstrom's syndrome patients, probably caused by release of the protein from activated leukocytes. The decreased calprotectin values observed in the other patients, may be due to plasma dilution. Unexpectedly, the GBS patients were found to have high initial calprotectin levels in plasma but not in cerebrospinal fluid. In donors, normal and unchanged calprotectin concentrations were found throughout. PMID- 1411261 TI - What causes impaired glucose tolerance to deteriorate or normalize? AB - Twenty-five middle-aged subjects with impaired glucose tolerance (IGT) were analysed 5 years later, showing normal glucose tolerance in 28% and persistent glucose deterioration in 72%. Body mass index (strongly) and 2-h glucose levels were clinically useful predictors, in the newly detected IGT-subjects, of persistent glucose deterioration (IGT or NIDDM) 5 years later. The frequency of hypertension was 36% in the newly-detected IGT subjects. Five years later this frequency increased to 54% in the persistently hyperglycaemic group, and decreased to none in the normalized group. Predictors of hypertension at the follow-up were baseline blood pressure and parts of the hyperinsulinaemic syndrome, such as serum triglyceride at baseline, BMI and 2-h glucose at the follow-up. Microalbuminuria (greater than 20 mg day-1) was not found at the 5 years follow-up, either if the subjects then had NIDDM, IGT or normal glucose tolerance. ECG abnormalities (ST segment and T wave changes) were two-fold more prevalent in the group with IGT or NIDDM than in the normalized group at the follow-up. Predictors were baseline BMI and incremental BMI. In conclusion, obesity and high 2-h glucose in newly-detected IGT-subjects seemed to predict the persistence of IGT 5 years later. Hypertension, but not microalbuminuria, was frequent when glucose deterioration persisted. PMID- 1411262 TI - Measurement of CA 125 by an automated microparticle enzyme immunoassay; comparison with a manual enzyme immunoassay. AB - The technical characteristics and the clinical usefulness of a new automated microparticle enzyme immunoassay (Abbott IMxR CA 125) for cancer antigen 125 (CA 125) in serum were investigated. The microparticle enzyme immunoassay (MEIA) had a high degree of practicability and a short turn-around-time. The imprecision (2.5-6.4%), detectability (less than 1 kU l-1), and carryover (less than 0.01%) of the analysis were low and the recovery of CA 125 after dilution with serum from ovarian cancer patients was good. The antigen was measured in samples from 72 ovarian cancer patients by the MEIA and a well documented manual enzyme immunoassay (Abbott CA 125 EIA). The correlation between the CA 125 MEIA and EIA results was non-linear. CA 125 EIA values below 39 kU l-1 (95% CI: 36-42) gave higher MEIA results and EIA values above this level resulted in lower MEIA values. The marker was measured before second-look laparotomy of 57 ovarian cancer patients. Using different cut-off levels, the clinical information of CA 125 MEIA measurements was equivalent to that obtained by EIA. The relationship between the CA 125 EIA values and the corresponding MEIA results was complex and the clinician may have difficulties in interpreting the MEIA CA 125 results until the calibration has been approximated to that of EIA. Alternatively, clinical investigations should be performed to establish an upper reference limit of MEIA CA 125 values. PMID- 1411263 TI - Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy. AB - Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50 healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1, 128 (x/ divided by 3.5) U l-1 and 126 (x/ divided by 3.7) U l-1 (geometric mean (x/ divided by antilog SD)) in group 1, 2, 3 and 4, respectively. 1 U l-1 apo(a) approximates 0.7 mg l-1 Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411264 TI - Effects of nicotinic acid on glucose tolerance and glucose incorporation into adipose tissue in hypertriglyceridaemia. AB - Nicotinic acid 4 g daily was given to 28 weight-stable hypertriglyceridaemic patients. The aim was to study its effects on serum lipoprotein lipid levels, intravenous glucose tolerance (k-values) and glucose incorporation into subcutaneous adipose tissue (GLIAT) in vitro. The investigations were performed prior to the nicotinic acid therapy, after 6 weeks, and 6 months of drug treatment. Fasting blood glucose levels increased by 13%, whereas k-values fell by 26% after the nicotinic acid treatment. Decrease in k-values was predicted from the initial k-values (R2-value = 0.76). GLIAT increased by 76%, while in the subgroup of eight patients, treated for 6 months with nicotinic acid, GLIAT increased by 331%. The changes in k-values and GLIAT were not significantly interrelated. Serum triglyceride levels were strongly decreased. The most likely explanation for the decrease in intravenous glucose tolerance is that nicotinic acid stimulates glucose output from the liver and that this effect outweighs the stimulating effects of the drug on glucose utilization in extrahepatic tissues. The latter is reflected by the increased uptake of glucose in adipose tissue. A stimulated GLIAT, reflecting formation of alpha-glycerophosphate in adipose tissue, might contribute to the reduction of serum triglyceride levels induced by nicotinic acid, since alpha-glycerophosphate is the acceptor of fatty acids assumed to be liberated from circulating triglycerides by lipoprotein lipase. PMID- 1411265 TI - Effects of nicotinic acid treatment on fatty acid composition of plasma lipids and adipose tissue in hyperlipidaemia. AB - Effects of 6-week treatment with 4 g daily of nicotinic acid on fatty acid composition in different serum lipids and in adipose tissue glycerides were studied in 31 hyperlipidemic patients. The percentages of eight fatty acids in triglycerides, phospholipids and cholesteryl esters of whole plasma as well as in subcutaneous adipose tissue glycerides were measured. Nicotinic acid treatment produced decreases in triglyceride and total cholesterol concentrations of VLDL and LDL, whereas HDL total cholesterol levels in serum increased after drug therapy, all p less than 0.01. There were reductions in the relative contents of myristic acid in plasma phospholipids (from 0.4% to 0.3%; p less than 0.05) and cholesteryl esters (from 0.9% to 0.7%; p less than 0.001). There were decreases in the percentages of stearic acid in plasma phospholipids (from 17.0% to 15.0%) and cholesteryl esters (from 1.2% to 1.0%; both p less than 0.001). The relative contents of polyunsaturated fatty acids, mainly linoleic acid, in plasma phospholipids were increased (from 32% to 33.5%; p less than 0.05). There were reductions in the linolenic acid contents of adipose tissue (from 1.5% to 1.1%) and plasma triglycerides (from 1.1% to 0.8%), both p less than 0.05, possibly indicating increased conversion of linolenic acid to prostaglandins. There was no relationship between changes in the percentages of individual fatty acids and changes in triglyceride or total cholesterol levels of whole serum and its VLDL, LDL and HDL fractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411266 TI - Presence of bile acid metabolites in serum, urine, and faeces in cirrhosis. AB - Studies have been made of the presence of bile acid metabolites in ten patients with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, indicating only mild impairment of liver function, whereas the remaining two patients comprised Child group C. A complex mixture of bile acids was isolated from serum, urine, and faeces, and 26 bile acids were identified by gas-liquid chromatography coupled to mass spectrometry. Identification was made of the primary bile acids, cholic (C) and chenodeoxycholic (CDC) acid, and metabolites of these bile acids converted through 7-dehydroxylation, keto-formation, 6-hydroxylation, 1 beta-hydroxylation, allo-formation or nor-formation. All of the bile acids have previously been described either in healthy humans or patients with hepatobiliary disease. With the exception of C, CDC, and deoxycholic acid, all of the bile acids were present only infrequently, and none of the bile acids was pathognomonic for liver cirrhosis. The proportion of metabolites of the primary bile acids C and CDC was similar to that previously reported in healthy humans, the lowest proportion being recorded in the Child group C patients. Repeated determinations of the metabolite pattern in two patients showed large variations, indicating that the bile acid metabolism varies from time to time. We conclude that in mild cirrhosis, no significant alterations in microbial or hepatic transformation of bile acids seem to occur. PMID- 1411267 TI - Analysis of unconjugated bilirubin in serum by reversed-phase high performance liquid chromatography. AB - A high performance liquid chromatographic method for the analysis of unconjugated bilirubin in neonatal serum is presented. Bilirubin was dissociated from protein with caffeine reagent and extracted with chloroform. An isocratic, reversed-phase HPLC system based on a C18 column was used. Bilirubin was detected at 450 nm. Bilirubin SRM 916a from National Institute of Standards and Technology, USA was the primary calibrator. An average recovery factor of 0.996 (SD = 0.018; N = 16) was obtained for bilirubin added to neonatal cord sera. The measurement range extended from 25 to 500 mumol l-1 L-1. The method is proposed as a reference method for unconjugated bilirubin in neonatal sera. PMID- 1411268 TI - Root canals in one-rooted maxillary second molars. AB - The Royal Dental College, Copenhagen, houses an extensive collection of human teeth extracted in Denmark. The collection currently contains 104 one-rooted, permanent maxillary second molars. The root complex on these teeth was sectioned at the junction between the coronal and the apical halves, i.e. mid-root, and at the junction between the middle and the apical thirds, i.e. apically. Using a stereomicroscope we then registered, mid-root and apically, the following variables: canal number, canal position, and canal cross-section. Mid-root there was 1 centrally located root canal in 25.96% of the teeth examined; 2 canals were observed either mesially and distofacially, mesiofacially and distally, or facially and lingually in 34.62%; 3 canals positioned mesiofacially, distofacially, and lingually were found in 39.42%. At the same level 63.51% of the canal cross-sections were non-circular, whereas 36.49% of the canals had a circular cross-section image. The non-circular canal cross-sections could more specifically be characterized as C-shaped, Y-shaped, hourglass-shaped or the root canal had a greater faciolingual than mesiodistal extension or, respectively, a greater mesiodistal than faciolingual extension. Apically there was 1 centrally located root canal in 35.58%; 2 canals were observed with a position either mesially and distofacially, mesiofacially and distally, or facially and lingually in 37.49%; 3 canals located mesiofacially, distofacially, and lingually were found in 26.92%. At the apical level, 64.32% of the root canal cross-sections were non-circular, whereas 35.68% of the canals showed a circular cross-section. The results presented here are aimed at: clinical dentists, endodontists, and dental morphologists. PMID- 1411269 TI - Effects of phosphonoformic acid and 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) on distribution of tetracycline in the developing rat molar. AB - Tetracycline was used as a marker to study the effect of phosphonoformic acid and 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) on the mineralization of the developing dental hard tissues. Groups of young rats were given a single subcutaneous injection of tetracycline and at the same time were injected with a single dose of either phosphonoformic acid or HEBP (10 mg P/kg b.w.). Alternatively, rats were injected with the tetracycline after different time intervals from the phosphonate injection. Rats were sacrificed at intervals ranging from 1 to 4 days. Frozen-sections were obtained at the level of the maxillary first molar and prepared for light and fluorescence microscopy. The results of the present study indicate that the distribution pattern of tetracycline in the developing dental hard tissues is greatly affected by the pathologic changes induced by phosphonoformic acid and HEBP. Both drugs caused similar changes in the pattern of tetracycline uptake in the developing enamel. There seems to be a direct relation between the presence of developmental defects of enamel and the degree of discoloration induced by tetracycline. Aberrations in the mineralization of dentin were caused only by HEBP. As demonstrated by this study, HEBP is capable of inducing a provisional inhibitory effect on dentin mineralization. PMID- 1411270 TI - Contribution of autogeneic membranous bone chips and bone paste to healing of rabbit skull defects. AB - In skeletal surgery, bone chips and bone paste are often used to facilitate bony repair. However, no comparative investigation between these forms of bone graft implantation has been undertaken. In this study four trephine skull defects were produced in each of 14 adult rabbits and inlays of bone paste and two separate amounts of bone chips were then implanted in each animal. The results were compared relative to a control defect and assessed by gross inspection, light microscopy, and contact radiography after periods of 4 and 15 wk. Bone chips offered only minor advantages over controls in the defects investigated and differences in bony regeneration between the diversified amounts of bone chips were negligible. After bone paste implantation, a cellular and mature bone was rapidly produced. The clinical significance of these findings is discussed. PMID- 1411271 TI - Oral function in patients wearing fixed prosthesis on osseointegrated implants in the maxilla: 3-year follow-up study. AB - Seventeen consecutive selected patients rehabilitated by means of a full maxillary bridge on osseointegrated implants ad modern Branemark were evaluated over a 3-yr period. Besides a subjective evaluation by means of a questionnaire an examination of the occlusal relationship, chewing force, chewing efficiency and interocclusal threshold level was performed before, immediately after, 3-6 months after, and finally 3 yr after bridge installation. All subjects were very pleased with the oral rehabilitation. The chewing force and the chewing efficiency development increased over time, while the threshold level for interocclusal detection remained unchanged. The clinical dysfunction index according to Helkimo indicated that there was no marked change in signs of dysfunction of the patients' masticatory systems during the observation period. From the present longitudinal investigation one can conclude that the replacement of a full maxillary denture with a fixed prosthesis on osseointegrated implants, facing a natural dentition or an osseointegrated implant supported bridge in the opposite jaw, leads to a progressive increase of chewing efficiency and chewing force, and a constant subjective improvement of jaw function, while no masticatory dysfunction seems to occur during the observation period. PMID- 1411272 TI - Occlusal control of mandibular elevator muscles. AB - Occlusal stability and mandibular elevator muscle function was studied in 25 women (20-30 yr of age). They had 27-32 fully erupted teeth with few treated occlusal surfaces, and craniomandibular function including mandibular mobility was normal. The aim was to analyze the influence of natural patterns of occlusal contact on electromyographic activity, unaffected by pain and functional disorders. Occlusal stability was assessed in the intercuspal and in lateral contact positions as the number of teeth with physical contact and the number of opposing pairs of teeth in contact. Electromyographic activity was recorded by surface electrodes over anterior and posterior temporalis and masseter muscles. In general, positive correlations were found between occlusal stability in intercuspal position and moderate to strong static and dynamic contractions, most significant in masseter muscles, indicating that forceful contraction of these muscles implies stable occlusion. Systematically, the duration of activity during chewing was negatively correlated with occlusal stability in the intercuspal position, most pronounced in working-side muscles. This pointed to shorter contractions with stable occlusion and is interpreted as the result of less need for stabilizing activity. It is concluded, that the correlations between occlusal stability and elevator muscle function are probably based on feedback mechanisms from periodontal pressoreceptors. PMID- 1411273 TI - Dummy- and finger-sucking habits in young Swedish and Norwegian children. AB - The prevalence of dummy- and finger-sucking habits in 3-yr-old children was registered in four different areas of Sweden and Norway. In Norway 245 children were examined and in Sweden 171 children. The Swedish children were more prone to develop a dummy-sucking habit as well as to prolong it. About 10-19% of the children in the different groups become finger-suckers. Very few of these finger suckers had stopped sucking at 3 yr of age. The highest rate of non-suckers was found among the children from Karasjok/Kautokeino in northern Norway, who were mainly of Lappish origin. PMID- 1411274 TI - Effect of temperature and duration of post-cure on selected mechanical properties of resin composites containing carboxylic anhydrides. AB - Resin composites containing carboxylic anhydrides have recently been formulated for use as inlay materials. To optimize the post-cure, the present study measured the effect of post-cure temperature and duration on four mechanical properties of anhydride-containing resin composites. Temperatures were varied between 37 degrees C and 225 degrees C, and durations were varied between 0 and 24 h. An optimum in strength and stiffness was found when post-cure temperatures of 125 150 degrees C were used. Strength and stiffness were found to increase with increasing duration of post-cure. Due to discoloration of the resin composites when post-curing for 6 or 24 h, a post-cure period of 1 h was preferred. PMID- 1411275 TI - Dental caries and Streptococcus mutans in a rural child population in Iceland. AB - In spite of having a high socioeconomic standing, in Iceland caries prevalence has remained stubbornly high. This study reports findings from a mixed fishing and farming community in East Iceland that has traditionally been associated with the highest prevalence of caries. A total of 188 children aged 3-16 yr (96.4% of residents of that age group) were examined. At 6 yr the mean dmfs score was 4.1, DMFS 0 and 48% were caries-free. The mean DMFS score at 12 yr was 4.7 and 22.6% remained caries-free but at 16 yr the DMFS score was 11.6 and no children were caries-free. Caries was unevenly distributed within each age group and was more prevalent among residents of the fishing town than the surrounding farming district. In a pilot study conducted in 1989 mean counts of Streptococcus mutans for children aged 4-7 yr were 2.6 x 10(5) cfu/ml and declined to 4.6 x 10(4) cfu/ml in 1990 after a program of chlorhexidine brushing had been added to the routine caries preventive measures adopted in this community. It may therefore be possible to screen Icelandic children for caries risk and apply preventive measures to those demonstrated to be most in need. PMID- 1411276 TI - The intestinal permeability barrier. A hypothesis as to its regulation and involvement in Crohn's disease. PMID- 1411277 TI - Primary sclerosing cholangitis in patients with ulcerative colitis. AB - The prevalence of primary sclerosing cholangitis (PSC) in patients with ulcerative colitis (UC) attending the Depts. of Medical and Surgical Gastroenterology, Aalborg Hospital, during a 12-year period, was determined. All patients with an alkaline phosphatase (ALP) value above the normal range were investigated. Of 305 patients with UC, 24 patients had elevated ALP values, and 11 of these (3.6% of the study population), 4 males and 7 females, were found to have PSC by direct cholangiography. In five patients the disease worsened (two patients died of cholangiocarcinoma), in four it was stationary, and in two patients the disease improved during a mean observation period of 6 years. No differences in location of disease, disease activity, or duration of disease were found between patients with UC and PSC and patients with UC without PSC. The ALP values were raised to a mean of 3.7 times the upper normal limit (observed range, 1.5-5.5 times the upper normal limit). Aspartate aminotransferase was moderately elevated in most patients, but no other abnormal biochemical liver test results were observed at onset. The results of our study indicate that PSC is the major cause of raised ALP values in patients with UC; thus cholangiography should be performed in UC patients with unexplained elevated ALP levels. A prognostic indicator is needed to predict the individual prognosis and to determine the optimal timing of liver transplantation. PMID- 1411278 TI - Cellular distribution of a colonic adenoma-associated antigen as defined by monoclonal antibody Adnab-9. AB - Adenomatous colonic polyps constitute a precursor for colorectal cancer. Antibodies to these precancerous lesions might identify specific early tumor antigens. Adnab-9 is a murine monoclonal antibody raised against membranes of colonic adenomas. Adnab-9 binding in colonic washings (effluent) correlates with the presence of colorectal cancer. Immunohistochemical staining with Adnab-9 shows cytoplasmic reactivity in scattered cells in 4 of 31 adenomatous tissue sections, 0 of 14 sections of colorectal cancer cells, and 1 of 8 normal appearing colonic mucosa specimens examined. Adnab-9 recognized a dominant M(r) 87,000 protein species in tissue extracts in the membrane-bound fraction of effluent by Western blotting. Adnab-9 binding by enzyme-linked immunosorbent assay in adenomatous extracts is higher than cancer or normal tissue, is membrane bound, and is absent from established colorectal cancer cell lines. This distribution and nature of immunostaining suggest that Adnab-9 recognizes a determinant associated with the membrane component of a subpopulation of adenoma cells which may have a role in early colorectal neoplasia. PMID- 1411279 TI - Pancreatic atrophy in rats produced by the cholecystokinin-A receptor antagonist devazepide. AB - According to recent reports, the powerful and selective cholecystokinin (CCK)-A receptor antagonist devazepide (also referred to as L-364,718 or MK-329) is without effect on the weight of the pancreas. This has been interpreted to mean that basal and meal-stimulated endogenous CCK does not play a major role in the normal maintenance of the pancreas. In the present study we show that continuous subcutaneous infusion of devazepide effectively and dose-dependently reduced the weight of the pancreas both in normal rats and in hyperCCKemic rats (because of pancreaticobiliary diversion). The maximum reduction of the pancreatic weight was 40%. Maximum or near-maximum effects were seen with a dose of 200 micrograms/kg/h. The DNA content of the pancreas was also reduced. The reduction in weight and DNA content of the pancreas was maximal after 10 days. Provided that devazepide acts solely by inhibiting CCK-A receptors, we can conclude that endogenous CCK plays an important role in both normal and stimulated growth of the rat pancreas. PMID- 1411280 TI - Role of the antrum in the gastric emptying of a non-nutrient liquid in the rat. AB - Forty male Wistar rats underwent liquid gastric emptying analysis with a non nutrient liquid--99mTC-tin colloid in physiologic saline. Twenty then had two thirds resection of the glandular stomach with Billroth-II-type reconstruction. Twenty served as controls: 10 unoperated and 10 with a laparotomy alone. Emptying was studied weekly for 4 weeks, then monthly for 4 months. Emptying was unchanged in unoperated controls. Laparotomy alone caused delayed emptying for 2 months (p less than 0.05). After Billroth-II resection emptying was delayed for 4 months (p less than 0.01). This delay included both the early and late phases of gastric emptying. We conclude that a laparotomy alone delays gastric emptying. The addition of an antrectomy causes a greater emptying delay, which persists for longer than that due to laparotomy alone. Thus, in a situation in which the small bowel and gastric feedback mechanisms are inoperative, the antrum is seen to play an important role in the gastric emptying of liquids. This supports the concept in man that antral contractions are important in ensuring the normal active emptying of liquids from the stomach. PMID- 1411281 TI - Cardiovascular effects of omeprazole and famotidine. AB - In a randomized, placebo-controlled, double-blind, crossover comparison, 12 patients with congestive heart failure (New York Heart Association class II) and dyspeptic complaints were treated orally for 1 week each with placebo, 40 mg omeprazole daily, and 40 mg famotidine daily. Non-invasive haemodynamic measurements were taken on the last day of treatment. Although omeprazole did not alter cardiac performance in impedance cardiography and mechanocardiography, the administration of famotidine led to a significant fall in stroke volume and cardiac output as compared with placebo (both p less than 0.05). Thus, omeprazole did not exert any relevant cardiovascular effects, in contrast to the H2-receptor antagonist famotidine. PMID- 1411282 TI - Experimental colonic inflammation and ulceration. Permeation of a water-soluble contrast medium as a measure of 'disease' activity. AB - The aim of this study was to investigate the permeation of an isosmolar water soluble X-ray contrast medium (CM) from the unperforated colon after experimental induction of inflammation and ulceration. One hundred and sixty-five male rats were included. In 110 rats 0.25 ml of 40% ethanol + 15 mg or 30 mg trinitrobenzene (TNB) was instilled into the colon, 7-9 cm proximal to the anus, inducing different degrees of inflammation. Fifty-five rats served as controls and had 0.25 ml saline instilled with the same procedure. At 7, 14, 21, and 28 days 3 ml of the non-ionic CM iodixanol was applied as an enema, and subsequently all urine was collected for the next 4 h. High-performance liquid chromatography analyses of the urine showed a positive relation between the severity of inflammation/ulceration in the colonic wall as assessed by a macroscopic damage score and the amount of CM excreted in the urine. Water-soluble contrast media may have prospects of combining functional tests of intestinal membrane dysfunction with segmental exposure control. PMID- 1411284 TI - Simultaneous administration of lactulose and 51Cr-ethylenediaminetetraacetic acid. A test to distinguish colonic from small-intestinal permeability change. AB - In normal adults intestinal permeation of ingested 51Cr ethylenediaminetetraacetic acid (EDTA) is greater than that of lactulose. This difference is abolished in patients with ileostomies, suggesting that it results from colonic permeation of 51Cr-EDTA, which, unlike lactulose, resists bacterial degradation. To investigate the effect of an increase in colonic permeability on absorption of the two molecules, lactulose (5 g) and 51Cr-EDTA (50 microCi) were given orally in isosmolar solution to 11 patients with colitis, and their 24-h urinary excretion measured. By comparison the effect of an increase in small intestinal permeability induced by ingestion of a hyperosmolar solution (4240 mosm/l) was measured in 10 healthy adults. Hyperosmolar stress increased the 24-h urinary excretion of 51Cr-EDTA above the normal mean + 2 standard deviations (3.31%) in all 10 healthy subjects, and in all of these excretion of lactulose was also increased (greater than 1.06%). In contrast, although seven colitics had a urinary excretion of 51Cr-EDTA above the normal mean + 2 SD, in only two of these patients was recovery of lactulose increased. This suggests that simultaneous administration of lactulose and 51Cr-EDTA may enable permeability changes affecting the colon alone to be distinguished from those involving the small intestine. PMID- 1411283 TI - Effects of the M1 muscarinic receptor antagonist pirenzepine on gastric mucus glycoprotein in rats with or without ethanol-induced gastric damage. AB - Changes in gastric mucus glycoprotein (mucin) isolated from pirenzepine-treated rats with or without ethanol (50%)-induced gastric damage were studied. The prior administration of pirenzepine inhibited significantly and dose-dependently the occurrence of macroscopically observable hemorrhagic lesions induced by treatment with ethanol. The gastric mucosa was separated into the surface mucosa, including the mucus gel layer, and the deeper mucosa by mechanical scraping, and the mucin in each was isolated. In ethanol-treated animals the mucin content of the deep corpus mucosa was significantly reduced to 68% the control value. This reduction was inhibited by pretreatment with pirenzepine. In the surface mucosa mucin content was also reduced to 48% of control value by ethanol treatment, but pirenzepine pretreatment increased mucin content to 235% the control value. Total mucin content in the entire stomach essentially resumed the control level by pretreatment with 100 mg/kg of pirenzepine. A single oral administration of pirenzepine (100 mg/kg) caused no change in total mucin content, but mucin in the deep corpus mucosa selectively and significantly increased to 124% the control. These and the results of carbohydrate analysis of purified mucin indicate that pirenzepine administration possibly accelerates the secretion of accumulated deep corpus mucus, retains this deep mucus on surface mucosal mucus, and protects the gastric mucosa in ethanol-induced gastric damage. This may be related to the antiulcerogenic effects of pirenzepine. PMID- 1411285 TI - Evaluation of different laboratory tests and activity indices reflecting the inflammatory activity of Crohn's disease. AB - In a prospective study we compared the usefulness of various laboratory tests (albumin, alpha-1-proteinase inhibitor (A1PI), cholinesterase (CHE), C-reactive protein, erythrocyte sedimentation rate, hematocrit) and activity indices (CDAI, VHAI) in relation to the disease activity by endoscopic criteria. Except for hematocrit highly significant differences (p less than 0.0005) of the mean values of all test results were found for patients without or with slight mucosal lesions compared with patients with severe inflammation of the mucosa. Further analysis of the data indicates the highest test efficiency (84%), sensitivity (80%), and specificity (88.6%) for CHE. CHE showed good correlations to all other tests; the highest correlation was found between CHE and VHAI (r = -0.78). We suggest that a suppression of CHE synthesis mediated by endotoxins and cytokines rather than an increased intestinal loss explains the decreased CHE in severe Crohn's disease. It is concluded from the data that CHE is a useful test to assess the inflammatory activity of Crohn's disease. PMID- 1411286 TI - Interval cancers in screening with fecal occult blood test for colorectal cancer. AB - Interval cancers, which are cancers diagnosed in spite of one or more negative screening tests, were studied in a randomized population with Hemoccult-II for colorectal cancer in 61,938 persons between 45 and 74 years old. Three biannual screenings were performed from 1985 to 1991, and 52% of all the cancers detected after doing at least one Hemoccult-II test were interval cancers (81 persons). These were more advanced than cancers diagnosed after a positive Hemoccult-II test, of larger size, less frequently of Dukes stage A, more often invading neighboring organs, and less often resectable for cure. They were located in the rectum more often than cancers diagnosed by screening and cancers in controls. Otherwise, interval cancers did not differ from cancers in controls or cancers in non-responders, and all characteristics suggested that no delay in diagnosis resulted from one or more negative Hemoccult-II tests, compared with controls. However, even if screening with Hemoccult-II demonstrates a reduction in mortality from colorectal cancer, the present high number of interval cancers makes it necessary to look for other methods of screening populations for colorectal cancer. PMID- 1411287 TI - Calcitonin gene-related peptide: effect on contractile activity and luminal cross sectional area in the isolated, perfused porcine ileum. AB - Because calcitonin gene-related peptide (CGRP) is an abundant peptide in the enteric nervous system we studied the effect of intra-arterial infusions of synthetic human CGRP I in concentrations from 10(-10) to 10(-8) mol/l on contractile activity and luminal cross-sectional area in the isolated perfused porcine ileum, using manometry and impedance planimetry. The frequency of the basal contractile activity was 0.37 +/- 0.1 contractions per minute. CGRP induced phasic contractions, which at the highest dose were superimposed on tonic contractions, as determined by measurement of luminal cross-sectional area. The frequency of contractions dose-dependently increased to approximately 10/min at 10(-8) mol/l CGRP. The amplitude of contractions increased from a maximum of 35 cm H2O to 51 +/- 3 at 5 x 10(-9) mol/l CGRP and 52 +/- 6 cm H2O at 10(-8) mol/l CGRP. After the termination of CGRP infusion at the highest dose a short phase of up to 5 min with strong tonic contraction was observed. No phasic activity was detected by manometry during this phase. In conclusion, CGRP dose-dependently increased contractile activity in the pig ileum. CGRP may therefore participate in the regulation of small-intestinal motility in the pig. PMID- 1411288 TI - Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. AB - This study describes methods for extraction and quantification of calprotectin (L1 protein) in feces by enzyme immunoassay. This protein is a prominent antimicrobial component of neutrophils, monocytes, macrophages, and squamous epithelia. Calprotectin was stable in feces during storage for 7 days at room temperature. Small fecal samples taken from a 24-h feces collection gave a reliable estimate of calprotectin. Within-assay precision was 1.9%, and between assay precision 14.8%. In healthy subjects (n = 33) median fecal calprotectin was 2025 micrograms/l and in hospital controls (n = 40) 10,500 micrograms/l. Median values in patients with Crohn's disease (n = 21) was 43,000 micrograms/l and in ulcerative colitis (n = 17) 40,000 micrograms/l. Fecal calprotectin was significantly correlated to fecal alpha 1-antitrypsin in the patients with Crohn's disease. Ten of 11 patients with gastrointestinal carcinomas had calprotectin level above the suggested reference limit of 6740 micrograms/l. PMID- 1411289 TI - Gastric emptying in infants with gastroesophageal reflux. Ultrasound evaluation before and after cisapride administration. AB - The present study aimed to evaluate gastric emptying in children with gastroesophageal reflux (GER) by means of real-time ultrasonography, on the basis of measurements of the cross-sectional area of the gastric antrum. Twelve children with GER were studied (seven males, five females; age range, 3-13 months) and compared with 12 normal control children (six males, six females; age range, 3-13 months). The diagnosis of GER was confirmed by 24-h esophageal pH monitoring. The GER patients had a significantly greater antral area than the controls at 90, 105, and 120 min after eating a standard meal (cow's milk formula, 300 ml/m2 body surface area); in addition, final gastric emptying time was significantly greater in the patients than in the controls (145 +/- 36.9 versus 78.7 +/- 19.3 min; p less than 0.0025). After 8 weeks of treatment with cisapride (0.3 ml/kg, three times a day) 24-h esophageal pH-monitoring and ultrasonography studies were repeated in the patients. The total percentage reflux time was significantly lower (p less than 0.038), and ultrasonography showed a decreased antral area at all the various study times, with no significant difference between patients and controls; final gastric emptying time was also significantly lower than before treatment (p less than 0.009). Furthermore, in the GER patients there was a significant correlation between gastric emptying time and the sum of the various reflux times recorded in the 2 h after all meals over the 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411290 TI - Computer-aided analysis of gastrointestinal pressure recordings. Comparison with manual scoring. AB - The aim of the present study was to compare computer-based and visual/manual scoring of pressure recordings from the gastric antrum and duodenum. The computer system was based on three separate principles of recognition: moving average, tracking base line, and threshold filters. Computer scoring resulted in the detection of more contractions than visual/manual scoring, owing to inclusion of artefacts of duration and amplitude above the selected thresholds. Owing to its unreliability, visual/manual scoring led to inclusion of some contractions of below-borderline amplitude or duration. The median difference in the frequency of contractions was, however, 0 min-1. There was close agreement on amplitudes of contractions. As the differences between visual/manual analysis and computer aided scoring by the present system are of an unimportant magnitude and as computer-based scoring is consistent, we conclude that computer-aided analysis is preferable to visual/manual analysis. PMID- 1411291 TI - Treatment and prophylaxis of chemotherapy-induced gastrointestinal complaints. AB - Ninety-eight patients (48 male, 50 female; age median, 56 years; range, 25-85 years) with solid tumors (21 breast cancers, 6 sarcomas, 2 colorectal cancers, 1 pancreatic carcinoma, 1 hypernephroma, and 1 lung cancer) and hematologic neoplasms (24 multiple myelomas, 32 lymphomas, and 10 myeloproliferative syndromes) were recruited into the study. The patients received at least three cycles of chemotherapy with alkylating substances, anthracyclines, antimetabolites, and vinca alkaloids, with or without corticosteroids. A total of 325 cycles of chemotherapy were administered. The symptoms were evaluated by means of a score system on the basis of which heartburn, sensation of repletion, nausea, and cramps were assessed by incidence and degree of severity. Before initiation of concomitant therapy with sucralfate, 47 patients (48%) had symptoms during chemotherapy (heartburn, sensation of repletion, nausea, cramps). After initiation of therapy with sucralfate these symptoms improved in 42 patients (89%); in 6 patients there was a transitory increase in heartburn and nausea. All other patients remained without symptoms in spite of chemotherapy. The evaluation of the patient population as a whole showed a significant decrease of chemotherapy-induced heartburn (p less than 0.01) and nausea (p less than 0.01) during sucralfate therapy. This was tolerated extremely well; side effects were not observed. To summarize, this prospective clinical study shows that sucralfate is an effective and suitable therapeutic principle in long-term therapy for the treatment and prophylaxis of chemotherapy-induced gastrointestinal complaints. PMID- 1411292 TI - Conservative treatment of stress ulcer bleeding: a new approach. AB - Stress ulcer prophylaxis diminishes but does not eliminate the risk of severe bleeding from this complication. In 70-80% of the cases the source of bleeding is hemorrhagic gastritis. No controlled studies exist which have in particular investigated conservative therapy in patients with stress-induced hemorrhage. Even effective measures to suppress gastric acid secretion or to reduce splanchnic blood flow are ineffective in 10-40% of intensive care unit patients with stress-induced bleeding. In these cases total gastrectomy has so far often been the only therapeutic approach. We report our experience with a new approach in treating severe stress-induced hemorrhagic gastritis after ineffective primary treatment with H2-receptor antagonists, pirenzepine and somatostatin. Continuous gastric lavage with 5-10 l ice-cold Ringer's solution was used until complete cessation of bleeding, as evident from clear lavage. Repeated administration of 12 g sucralfate (60 ml) at 2-h intervals for 24 h through a gastric tube was used to prevent recurrence of bleeding and to promote healing. Sucralfate was reduced on the 2nd and 3rd day to 20 ml 2-hourly and later to 10 ml 4-hourly. In four patients this treatment was used as an ultima ratio when the patients were already scheduled for total gastrectomy. A total of 23 patients were treated during a 7-year period; all of them responded successfully, and no patient required surgery. PMID- 1411293 TI - Follow-up of endoscopic gastritis after healing with sucralfate or an H2-receptor antagonist. AB - 48 patients in whom previous endoscopic signs of chronic gastritis had been abolished by treatment with either 1 g sucralfate three times daily or 40 mg famotidine at night were followed up for 3 months without further therapy. Cumulative endoscopic relapse rates at 3 months were 21.7% in the sucralfate group and 57.1% in the famotidine group (p = 0.017). All patients with endoscopic recurrence of gastritis also reported recurrence of dyspeptic symptoms of various degrees. Most patients with endoscopic relapse had persisting histologic gastritis, but up to 67% of subjects with histologic gastritis at the time of initial endoscopic healing did not have subsequent endoscopic or clinical recurrence. It is concluded that gastritis, especially if histologically active, tends to recur quickly after endoscopic healing and that early relapses are significantly more frequent after treatment with an H2 blocker than after sucralfate. PMID- 1411294 TI - Triple therapy with sucralfate is as effective as triple therapy containing bismuth in eradicating Helicobacter pylori and reducing duodenal ulcer relapse rates. AB - Duodenal ulcer relapse rates after therapy with sucralfate or bismuth are lower than those after H2-receptor antagonist therapy. This may be mediated by an antibacterial effect of these drugs on Helicobacter pylori. Bismuth has become an integral part of 'triple therapy' because of its documented anti-H. pylori effect. In vitro and clinical data suggest that sucralfate may also have an anti H. pylori effect. The aim of this randomized, prospective therapeutic trial was to compare the efficacy of triple therapy containing bismuth with that containing sucralfate and to determine the effect of therapy with these combinations on duodenal ulcer relapse. Forty H. pylori-positive duodenal ulcer patients were healed with omeprazole and randomized to receive either 1 g sucralfate four times daily or 120 mg bismuth compound four times daily. All patients received 400 mg metronidazole three times daily and either 250 or 500 mg tetracycline four times daily for 7-14 days. Thirty-five patients could be analysed. Overall eradication rates did not differ in the treatment groups (10 of 17 eradicated with sucralfate and 11 of 18 with bismuth). Relapse rates were significantly lower in the eradicated group (1 of 21 compared with 8 of 14 in the non-eradicated group) and did not differ between treatment groups in those patients not eradicated. A triple therapy regimen utilizing sucralfate appears to be as effective as the bismuth-containing regimen. PMID- 1411295 TI - Prevention of peptic ulcer relapse by sucralfate: mechanisms of action. AB - Sucralfate has a complex effect on the luminal and mucosal environment of the stomach and duodenum. Some of the actions are important in ulcer healing whilst others are important in preventing subsequent ulcer relapse. Although sucralfate has little direct effect on acid secretion, there is evidence that after ulcer healing with this drug, parietal cell responsiveness is reduced. This may in part be mediated by increased somatostatin release from gastric D cells and may be important in reducing ulcer relapse. Sucralfate has been shown to increase mucosal resistance to damaging agents, such as ethanol and aspirin. Studies have shown that this protective action may be related to the drugs effect on various protective zones such as the 'mucous-bicarbonate' barrier, mucosal hydrophobicity, epithelial cell function and morphology, and mucosal blood flow. These complex actions of sucralfate are in part related to direct interaction between the drug or its components and gastroduodenal tissues, and in part related to effects on various mediators of tissue injury and repair. PMID- 1411296 TI - Prevention and therapy of radiation-induced bowel discomfort. AB - In a double-blind randomized placebo-controlled study, including 70 patients treated with radiotherapy of localized malignancies in the pelvis, the effects of prophylactic sucralfate in preventing bowel discomfort were evaluated. Radiotherapy was delivered in a conventional manner with high-energy photons in a total dose of 62-66 Gy (target dose, 1.8-2.2 Gy) during 6.5 weeks. Dose granules of sucralfate or placebo were given 2 weeks after irradiation started and continued for 6 weeks. All analyses were performed blindly. The patients in the sucralfate group had significantly less problems with acute (5 weeks) and chronic (66 weeks) bowel discomfort. The consumption of loperamide was also reduced in the sucralfate group, and the weight decrease was less pronounced. No adverse effects were seen. Thus, sucralfate seems to be beneficial in minimizing the problems of bowel discomfort during and after irradiation of malignancies in the pelvis. These results are discussed in relation to other related observations. PMID- 1411297 TI - The Nobel Lectures in Immunology. Lecture for the Nobel Prize for Physiology or Medicine, 1980: Studies in histocompatibility. PMID- 1411298 TI - Speculations on immunosomatics: potential diagnostic and therapeutic value of immune homeostasis concepts. PMID- 1411299 TI - TCR gamma/delta+ cell subsets in the synovial membranes of patients with rheumatoid arthritis and juvenile rheumatoid arthritis. AB - Using a peroxidase/anti-peroxidase immunohistochemical staining method, we examined sections of inflammatory synovial membranes from 13 patients with juvenile rheumatoid arthritis (JRA) and 11 with rheumatoid arthritis (RA). The relative numbers of TCR gamma/delta+ cells and the proportions of V delta 1+ and V delta 2+ subsets were recorded in the areas of the membranes most heavily infiltrated by CD3+ cells. In the JRA group, the majority (8/13) of the membranes had TCR gamma/delta+ cells which contributed between 5 and less than 10% of the total number of CD3+ cells. In the RA synovial membranes examined, 5/11 samples had between 5 and 10% TCR gamma/delta+ cells, but in another 5 TCR gamma/delta+ cells contributed to between 10 and 20% of CD3+ cells. No significant difference was noted between the two patient groups. However, the range of values found in the RA membranes appeared to be slightly higher in comparison to previously reported values for RA synovial fluid, peripheral blood and eluted synovial membrane T cells. Analysis of the relative proportions of the V delta 1+ and V delta 2+ subsets revealed a significant dominance of V delta 1+ cells in RA membranes and approximately equal numbers of the two populations in the JRA patients. As the majority of peripheral blood TCR gamma/delta+ cells use the V delta 2 segment this suggests a preferential homing or expansion of the V delta 1+ cells in both RA and JRA synovium. The overall distribution pattern of the TCR gamma/delta+ and V delta 1+ and V delta 2+ cells was also recorded. These cells mostly accumulated in the lymphoid-like tissues and in the perivascular area in the tissues of both RA and JRA patients. Occasionally, augmented numbers of these cells were found in the subsynovial layer or in the loose connective tissue. In the majority of cases, only a few TCR gamma/delta+ cells were located in the synovial layer. The function and the possible pathogenetic importance of these TCR gamma/delta+ cells have not so far been determined. PMID- 1411300 TI - Membrane expression and function of complement receptors CR1 and CR3 on neutrophils from HIV-infected subjects: modulation by rTNF-alpha and rGM-CSF. AB - We evaluated membrane expression and function of complement receptors CR1 and CR3 on neutrophils from 27 HIV-positive (HIV+) subjects (14 in the CDC class III and 13 class IV) as well as their modulation in vitro by recombinant tumour necrosis factor-alpha (rTNF-alpha) and granulocyte-macrophage colony stimulating factor (rGM-CSF). While CR1 was expressed at similar levels on neutrophils from controls and HIV+ subjects, CR3 expression was significantly higher in CDC class IV subjects than in healthy controls. CR1 and CR3 expression was significantly increased after treatment of neutrophils with both cytokines, without differences between controls and HIV+ subjects. Similarly, the superoxide anion (O2-) production in response to C3-coated zymosan (C3zy) was significantly enhanced on neutrophils from CDC class IV subjects when compared with controls. rGM-CSF and rTNF-alpha treatment significantly enhanced the spontaneous as well as C3zy stimulated O2- production by neutrophils from controls and CDC class III subjects, and induced an upward trend in the CDC class IV group. These results indicate that the neutrophils of HIV+ patients are preactivated in vivo but they also indicate that these cells may correctly respond to a subsequent particulate stimulus as well as to activating cytokines. Our findings suggest that desensitization or functional exhaustion of complement receptors are not implicated in the abnormalities observed on neutrophils from HIV+ patients. PMID- 1411301 TI - Dopamine-induced lymphoma cell death by inhibition of hormone release. AB - Dopamine inhibits prolactin release from pituitary cells and seems to affect the release of several other hormones as well. We report here that dopamine may have similar effects on human B lymphoma cells leading to inhibition of production or release of endogenous factors required for cell viability and proliferation. Thus, addition of dopamine to serum-free cultures of Burkitt lymphoma cells (Raji, Namalwa, Daudi and Jijoye) resulted in rapid and extensive cell death while a myeloma cell line, SKO, appeared to be refractory to this treatment. The addition of FCS or supernatant from serum-free cultures of Raji or T24 bladder carcinoma cells could, to a variable degree, counteract the effect of dopamine, suggesting that dopamine acts by inhibiting the production of essential autocrine factors. When two of the hormones known to be under dopamine control, i.e. prolactin (PRL) and thyrotropin (TSH), were tested, they were able to prevent dopamine-induced cell death if combined with heparin. We further observed that the reducing agent 2-mercaptoethanol (2-ME), which is known to inhibit the binding of TSH to its receptor, displayed similar effects to those of dopamine and was strongly inhibitory for Burkitt lymphoma but not for myeloma cells. As expected from its blocking activity at the receptor level, the effect of 2-ME could not be reversed by adding exogenous factors. Contrary to its effect on B lymphoma cells, 2-ME is essential for growth of the murine T-cell lymphoma line CTLL. However, we show here that dopamine can fully compensate for 2-ME, suggesting that TSH or another factor under dopamine control is intimately involved in the regulation of T-cell growth. This study lends further support to the notion of an active interplay between the neuroendocrine and immune systems and emphasizes PRL and TSH as important regulators of lymphoid cell function. It also shows that these hormones may contribute to the autonomous growth pattern of B lymphoma cells and suggests a potential role for dopamine in the treatment of B cell tumours. PMID- 1411302 TI - Antigen-specific increases in the number of splenocytes expressing MHC class II molecules following restimulation with antigen in various physical forms. AB - To understand how a presentation system for antigens initiates an immune response and why it has a strong adjuvant activity, a number of parameters need to be analysed. In this study the frequency of spleen cells expressing MHC class II (Ia antigen) was determined after immunization of mice and restimulation of their spleen cells, in vitro, with influenza virus envelope proteins in different physical forms, namely iscoms, micelles and virus particles. All three forms of the antigen stimulated, in an antigen-specific manner, an increased proportion of spleen cells expressing MHC class II in the restimulation experiments. The induction of increased MHC class II expression was at least partly dependent on antigen-specific induction of IFN-gamma since an antibody to IFN-gamma partly inhibited the increase of MHC class II+ cells induced by iscom or by Concanavalin A. The iscom-borne antigens were superior to micelles to prime the immune response in vitro, indicating a capacity to induce memory cells. This primed immune response was readily recalled in vitro, as measured by IFN-gamma production and an increased number of MHC class II positive cells. PMID- 1411303 TI - Production of basic fetoprotein in human peripheral lymphocytes during blastic transformation. AB - To clarify the significance of basic fetoprotein (BFP) in lymphocytes, we investigated whether BFP is produced in lymphocytes during blastic transformation. Peripheral blood lymphocytes obtained from 14 adults were cultured under the stimulation of lectins. The concentration of BFP in the culture medium (extracellular BFP) was estimated serially. The incorporation of [6-3H]-thymidine was assayed simultaneously. The intracellular BFP was measured by dual flow cytometry for DNA and BFP. A lymph node was studied immunohistochemically. Serum BFP was measured in four cases of lymphocytic leukaemia. In two cases, dual staining was performed. The intracellular BFP of the mitogen-stimulated lymphocytes was increased within 24 h. The extracellular BFP was increased exponentially from 72 h. The extracellular BFP at 96 h did not correlate with the [3H]-thymidine incorporation. The intracellular BFP increase began in G1 phase. Immunostaining showed that the B cells also produced BFP. The serum BFP level in leukaemia was high in 1 of 4 cases and the leukaemic cells in two cases showed high intracellular BFP content. These observations indicate that BFP is produced in activated human lymphocytes and in lymphocytic leukaemic cells. The production of BFP during blastic transformation will be a useful new in vitro model for studying the biological role of BFP, and BFP labelling may offer some new possibilities for the study of lymphocytes. PMID- 1411304 TI - Use of an anti-idiotypic monoclonal antibody in studying amyloidogenic light chains in cells, urine and fibrils: pathophysiology and clinical implications. AB - A monoclonal anti-idiotype antibody (IgG1k MoAb 3B11D4) raised against the amyloidogenic DEP lambda chain dimer binds a conformational idiotope also present on the monoclonal DEP IgA immunoglobulin. MoAb 3B11D4 does not recognize the reduced and alkylated lambda chain monomers, nor the 15-17-kDa fibrillar light chain fragments which have the same N-terminal sequence of the urinary light chains. The lack of about 70 amino acid residues of the C terminal of the protein prevents the formation of the self-limiting dimer and may facilitate the deposition of the fragments into amyloid fibrils. MoAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning experiments demonstrate that this antibody has the capability to selectively eliminate the idiotype positive cells from peripheral blood. Antibodies with these characteristics could become a useful tool for better understanding the pathogenesis of the disease and for new therapeutic options. PMID- 1411305 TI - Epidemiological studies of penicillin resistance in Danish Staphylococcus aureus strains in the period 1977-1990. AB - During the period 1977-1990 the frequency of penicillin resistance increased from 78.7 to 87.5% among a total of 278,193 Danish Staphylococcus aureus strains from hospitalized patients. By combining these data with phage-type patterns the increase was shown to be caused by 1) the introduction and spread of mainly resistant strains of type 95 and the 94,96 complex; 2) an increased occurrence of strains of group II which during the observation period became more frequently penicillin resistant; and 3) a gradual disappearance of strains of group III and the 83A complex which showed a decreasing degree of penicillin resistance. During the observation period community acquired strains reached nearly the same level of penicillin resistance as the hospital-acquired strains, and the frequency of penicillin resistance did not increase during hospitalization among the predominant strains of type 95, group II and the 94,96 complex. S. aureus isolated from airways had a higher frequency of penicillin resistance mainly caused by increasing amount of penicillin resistant strains of group II. Strains from urine had a lower frequency of penicillin resistance. The total antibiotic consumption and the usage of beta-lactam antibiotics remained nearly unchanged during the observation period. The frequent use of beta-lactam antibiotics for airway infections might explain the possible selection of penicillin resistant strains of group II. PMID- 1411306 TI - HIV-2 infection in Denmark. AB - A collection of 3019 selected serum samples (ss), comprising 329 ss from intravenous drug abusers, 558 ss from homosexual men, 682 samples from persons attending a STD clinic, 100 ss from individuals of African origin, 300 ss from sexual contacts to Africans, 650 ss from Danish blood donors who resided in Africa greater than 2 years prior to donating the ss, and 400 ss with equivocal antibody reactions in an HIV-1 Western blot was tested for antibodies against HIV 2 by in-house HIV-2 ELISA and Western blot. Four ss were positive for antibodies against HIV-2. Three of the ss originated from West African men, the fourth belonged to the spouse of one of these men. Three of the samples presented with an uncharacteristic reaction in a HIV-1 Western blot. The study indicates that HIV-2 infection is not yet widespread in Denmark and that it remains closely related to West Africa. PMID- 1411307 TI - Intramuscular versus intradermal administration of a recombinant hepatitis B vaccine: a comparison of response rates and analysis of factors influencing the antibody response. AB - In an open controlled study 286 health care workers in Stockholm, Sweden, received 20 micrograms of a recombinant hepatitis B vaccine (Engerix B) by the intramuscular route, and 383 2 micrograms by the intradermal route. Seroconversion to protective anti-HBs levels (anti-HBs titre greater than or equal to 10 IU/l) was achieved in 94% of the i.m. and 89% of the i.d. vaccinees. Female sex, intramuscular vaccination, young age, and being a non-smoker were associated with a higher response rate and a higher geometric mean anti-HBs titre than male sex, intradermal vaccination, old age and being a smoker. If an acceptable response rate to protective anti-HBs levels of 85% is chosen, intradermal vaccination can be used as a cost reducing strategy for all women and for non-smoking men less than 30 years of age, as estimated in a logistic regression model. Due to the variable antibody response in different individuals, post vaccination testing for anti-HBs titres is recommended in health care workers, regardless of vaccination route. PMID- 1411308 TI - Spread of subclinical Chlamydia pneumoniae infection in a closed community. AB - Chlamydia pneumoniae infections may spread subclinically. The present investigation took place in a military setting. Sera drawn when the conscripts had entered their military service 2 months previously had been kept frozen and were available. In a camp with 500 people, 35 (7%) developed clinical symptoms of pneumonia. The infection was serologically verified with C. pneumoniae-specific micro-immunofluorescence technique. Of 40 healthy controls, 21 turned out to fulfil the serological criteria of infection, thus, representing subclinical cases. These 21 cases, when extrapolated to the whole camp, equalled a rate of 49% which, added to the 7% of pneumonic cases, gave a total infection rate of 56%. Pre-existing IgG antibodies were demonstrated in 10% of the pneumonic cases, 48% of the subclinical cases, and 89% of the non-infected, healthy controls. Without the access to pre-epidemic sera permitting us to establish 4-fold titre rises, the spread of subclinical C. pneumoniae infection would have been noted at 5%, and not 49% as here demonstrated. PMID- 1411309 TI - Serologically indicated pneumococcal respiratory infection in children. AB - Streptococcus pneumoniae infection was indicated serologically in 84 (19%) of 449 children hospitalized with middle or lower respiratory tract infection. Pneumococcal antigen was detected in acute serum in 28 patients, but in acute urine in only 2. An antibody response to type-specific capsular polysaccharides of S. pneumoniae was indicated in 27 patients and to a protein antigen, pneumolysin, in 25 patients, but to C-polysaccharide in only 10 patients. The observations mentioned above suggest that each serological test for pneumococcal etiology is insensitive, and to get an optimal result, a large panel of pneumococcal antigen and antibody assays must be used. Pneumococcal infection could be indicated serologically although no focus of infection, such as pneumonia or acute otitis media, or no laboratory evidence of bacterial infection as elevated values of C-reactive protein concentration, erythrocyte sedimentation rate or white blood cell count was present. Particularly antibody responses to pneumococcal pneumolysin were present in children without pneumonia or acute otitis media. Our results point out that no nonspecific parameter can be used for the selection of patients with probable pneumococcal etiology among children with respiratory tract infection. Concomitant viral infection, in most cases RSV infection, was present in a third of the children with pneumococcal infection. It is concluded that pneumococcal etiology should be actively sought for also in patients with viral respiratory infection, especially in young children with RSV infection. PMID- 1411310 TI - Pneumococcal finding in a sample from upper airways does not indicate pneumococcal infection of lower airways. AB - The presence of pneumococcus (Pnc) by antigen detection and culture was examined in nasopharyngeal aspirates (NPA) of 315 children hospitalized with middle or lower respiratory tract infection. Pnc was found in NPA from 115 (37%) patients, being demonstrated by antigen detection alone in 34 (30%), by culture alone in 26 (23%) and by both methods in 55 (48%) of Pnc-positive samples. Pnc findings in NPA were most common, 45-46%, in patients aged 1-4 years. Serological evidence of Pnc infection, based either on detection of Pnc antigen in serum or urine, or on demonstration of an antibody response to these antigens, was present in 31 (27%) of the 115 patients with and in 28 (14%) of the 200 patients without Pnc in NPA samples. In the 48 patients positive for Pnc in NPA samples both by antigen detection and culture the isolated Pnc strains were serotyped. In 45 (94%) of these the type/group of Pnc was the same by both methods indicating that the specificity of the antigen detection tests, latex particle agglutination and counterimmunoelectrophoresis, was high. To evaluate the diagnostic significance of Pnc antigen detection and culture in NPA, sensitivity, specificity and likelihood ratios were calculated; serological evidence of Pnc aetiology was used as a reference. For both methods, sensitivity was poor, less than 0.3, but specificity was good, greater than 0.8. It is concluded that the finding of Pnc by culture or antigen detection in NPA is no indication of Pnc respiratory infection. On the other hand, Pnc etiology is unprobable, if Pnc is not present in NPA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411311 TI - Severe Pasteurella multocida infections in pregnant women. AB - We report 2 cases of severe infections due to Pasteurella multocida, both occurring during pregnancy in previously healthy women. Both women had contact with animals (dog and cat) but neither of them had been bitten. Apart from a slight decrease in IgG levels, no immunological defects could be detected. Both women had received oral phenoxymethylpenicillin in the early phase of the disease, but still fell ill with severe infections. One woman had meningitis while the other suffered from cellulitis with deep abscess formation. PMID- 1411312 TI - Cell surface proteins of Helicobacter pylori as antigens in an ELISA and a comparison with three commercial ELISA. AB - Cell surface proteins of Helicobacter pylori were solubilized by extraction with acidic glycine buffer, N-octyl-glucoside, lithium chloride, and distilled water, and by sonication. The preparations were evaluated as antigens in ELISA to detect serum IgG responses in patients and healthy subjects. SDS-PAGE analyses of the preparations from a type strain (NCTC 11637) and of acidic glycine extracts of 4 clinical isolates showed multiple protein bands. The sera were classified as HP+ve and HP-ve by culture of biopsy and immunoblotting. Sera were considered positive for H. pylori if they detected the specific 120kD antigen or 4-5 other bands. 49 sera were HP+ve; the 51 HP-ve sera did not react in immunoblotting. 35/44 sera (80%) that reacted with the 120kD antigen demonstrated high titers in ELISA with all antigen preparations, and the remaining 9(20%) sera gave discordant results. 4/5 HP+ve sera that did not react with the 120kD antigen, demonstrated high ELISA titers with all 5 antigen preparations. Glycine extracts of 3 isolates did not exhibit the 120kD protein, but were equally sensitive in ELISA. The role of 120kD antigen in our ELISA was not clear. Immunoblotting demonstrated that the 5 antigen preparations share similar antigenic components. All preparations were similarly high in sensitivity and specificity, indicating that surface antigens could be satisfactorily used in our ELISA. Our ELISA using the glycine extract was compared with commercial H. pylori ELISAs developed by Bio-Rad Laboratories, USA (GAP ELISA), Roche, Switzerland (EIA 2G), and Whittaker Bioproducts, USA (Pyloristat).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411313 TI - A pilot study of piperacillin and ciprofloxacin as initial therapy for fever in severely neutropenic leukemia patients. AB - We studied the efficacy of piperacillin and ciprofloxacin as initial parenteral therapy in 41 adult patients with leukemia who developed 47 febrile episodes during severe neutropenia following chemotherapy. 40 patients (98%) survived their febrile episode(s), whereas 1 patient died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 24/47 episodes (51%) had been successfully treated. These 24 favourable responses were seen in 15/24 (63%) microbiologically documented infections and 9/19 (47%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 46 episodes were evaluable, and 28 (61%) had responded successfully to piperacillin and ciprofloxacin. Successful treatment was most frequently observed in microbiologically defined infections, 18/23 (78%). Three of 5 (60%) Gram-positive, 11/12 (92%) Gram negative and 1 of 2 mixed bacteremias were successfully treated. In contrast, only 10/19 (53%) FUO and none of 4 clinically defined infections had responded. Thus, this pilot study indicates that piperacillin and ciprofloxacin may be a safe and effective combination for the treatment of febrile episodes in severely neutropenic leukemia patients, which merits further investigation in randomized trials. PMID- 1411314 TI - Hospital-acquired infections in Norway: a national prevalence survey in 1991. AB - A 1-day prevalence survey of hospital-acquired infections (HAI) was carried out in Norwegian somatic hospitals in 1991. The survey aimed at assessing the problem of HAI. 950 infections were found among the 14977 surveyed patients (prevalence rate 6.3%). HAI were more prevalent in combined intensive care units (prevalence rate 22%), surgical intensive care units (17%), haematological wards (15%), special care baby units (14%), and geriatric wards (14%). Urinary tract infections were most prevalent (33% of all HAI) followed by respiratory tract infections (21%) and surgical wound infections (17%). 157 (3.6%) of the 4382 patients who had undergone surgery, had a surgical wound infection. With a high response rate (76 out of 84 hospitals) and a sensitive method of screening the patients (chart review and bedside examination), this survey gives a fairly reliable measure of the prevalence of HAI in Norwegian somatic hospitals. PMID- 1411315 TI - Antibiotic susceptibility of upper respiratory tract pathogens in Sweden: a seven year follow-up study including loracarbef. Swedish Respiratory Tract Study Group. AB - The antibiotic susceptibility of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae was investigated in five different geographical areas of Sweden in 1990 and compared with results from similar investigations performed in 1983 and 1986. Tests on 100 isolates per species and laboratory were performed by the disk diffusion method, and 10% of the strains plus all resistant ones were sent to the central laboratory for determination of MICs of ampicillin, phenoxymethylpenicillin, cefaclor, loracarbef, erythromycin, tetracycline and trimethoprim/sulfamethoxazole. Beta lactamase production was found in 7% of H. influenzae and 71% of M. catarrhalis, and reduced susceptibility to penicillin in 3% of S. pneumoniae. Low frequencies (1-3%) of tetracycline resistance were found in H. influenzae and in the 2 streptococcal species, in which also less than 1% of the strains were resistant to erythromycin. Resistance to trimethoprim/sulfamethoxazole occurred in 7% (range 3-14%) of H. influenzae and in 3% of S. pneumoniae. Cefaclor was active against all streptococci except against S. pneumoniae with reduced susceptibility to penicillin. It was active against beta-lactamase negative strains of M. catarrhalis but had, according to the SIR-system, intermediate activity against H. influenzae. Loracarbef was twice as active as cefaclor against H. influenzae but equally active against the 3 other species tested. PMID- 1411316 TI - A 56-month prospective surveillance study on the epidemiology of aminoglycoside resistance in a Belgian general hospital. AB - In this survey, we studied the effect of extensive amikacin usage on the epidemiology of aminoglycoside resistance in a general hospital. The baseline resistance in the 12 months before amikacin was 5.8% for amikacin, 15.2% for gentamicin, 16.4% for tobramycin and 14.0% for netilmicin. During the following 44 months, amikacin was the aminoglycoside of first choice. In the first 2 years of this phase, resistance to amikacin did not change significantly. Later, amikacin resistance rose significantly, mainly due to the introduction of amikacin-resistant Enterobacter aerogenes strains. In general there was a significant decrease in resistance to gentamicin and tobramycin. Resistance mechanisms were examined in 380 strains. AAC(3)V, and AAC(6')I alone or coupled with ANT(2") or AAC(3) were the most prevalent enzymes. In the amikacin phase, we noticed a significant increase of strains harbouring the AAC(6')I enzyme, while strains with the AAC(3)V were less frequently isolated. Strains with permeability resistance did not become more prevalent during the period of extensive amikacin use. PMID- 1411317 TI - A comparison of netilmicin and tobramycin therapy in patients with renal impairment. AB - We evaluated the toxicity and efficacy of netilmicin and tobramycin in 89 older adults with serious bacterial infections and pre-existing renal impairment in a prospective, blinded, randomized trial. Complete resolution or improvement of infection occurred at 34/36 (94%) evaluable sites in netilmicin-treated patients and at 26/31 (84%) evaluable sites in tobramycin-treated patients. 10/44 (23%) netilmicin- and 7/45 (16%) tobramycin-treated patients experienced nephrotoxicity during treatment. The mean serum creatinine level improved significantly at the end of therapy compared to pre-treatment in those patients who did not experience nephrotoxicity in both treatment groups. 5/19 (26%) netilmicin-treated patients and 2/18 (11%) tobramycin-treated patients assessable for ototoxicity experienced decrements in auditory thresholds. Ototoxic netilmicin-treated patients had higher serum netilmicin levels than did non-ototoxic patients. Patients who experienced ototoxicity were not more likely to have experienced nephrotoxicity. The rates of toxicity were not statistically different and were similar to those seen in studies of patients with normal pre-treatment renal function. PMID- 1411318 TI - First-year infections after initial hospitalization in low birth weight infants with and without bronchopulmonary dysplasia. AB - Symptoms of infection, specific infections, antibiotic course and hospitalizations were evaluated prospectively by using monthly questionnaires after initial hospitalization in 73 low birth weight (LBW) infants (less than 1751 g) and a subgroup of 19 infants with bronchopulmonary dysplasia (BPD) compared with 63 full-term controls matched for age, sex and home locality. The immunoglobulin G, A, M and E levels of the LBW infants were measured at corrected ages of 1, 2, 4, 6, 8, 10 and 12 months. The LBW infants, the subgroup with BPD and their controls had similar frequencies of infectious symptoms and episodes of infection. Dyspnoea and lower respiratory tract infections often caused by respiratory syncytial virus (RBV) were more frequent and more severe among LBW and especially BPD infants compared with controls. Male sex, a large family and day-care were significant risk factors for illness. The IgG levels of the LBW infants were subnormal at the corrected age of 1 month, but otherwise immunoglobulin levels were normal. The results suggest that LBW infants and especially those with BPD are prone to lower respiratory tract infections and should be considered candidates for immunoprophylaxis against RBV. In order to reduce morbidity home care is preferable to day-care. PMID- 1411319 TI - Infectious diseases and day-care centre environment. AB - During the period from September 1986 to May 1987 all 25 day-care centre departments in the residential district of Teleborg in Vaxjo were studied to discover the frequency of absence due to infection. Mean absence/department was 6.6% (SD 2.2), with a range from 3.9% to 10.2%. During the period from September 1989 to May 1990 a follow-up study used the same methods to investigate 7 departments, which in the first study had shown the highest and lowest rates of absence due to infection. In addition, the carbon dioxide content in indoor air was measured in all departments in the district. The new measurements showed that the average absence due to infection in the 7 departments had fallen from 7.5% (SD 2.9) to 5.6% (SD 1.4). It was not possible to reproduce the division seen in the first study into departments with high and low absence rates. The variations in infectious morbidity observed could not be explained by differences between the departments as regards physical environment or working routines. By contrast, a considerable difference as regards carbon dioxide content in indoor air was seen between the 3 departments housed in converted dwellings and the 4 departments in purpose-built day-care centres; the mean values were 822 ppm and 458 ppm, respectively (Mann-Whitney U-test; p = 0.028). PMID- 1411320 TI - Rat bite fever in a Greek child. AB - Rat bite fever was diagnosed in a 10-year-old boy in a rural area of south-west Greece. The clinical presentation was typical for this disease and the relevant causative agent (Streptobacillus moniliformis) was isolated from blood cultures of the febrile patient. Erythromycin treatment was efficient. Although extremely rare in continental Europe, this infection must be taken into account as a potential hazard of a rat bite. PMID- 1411321 TI - Rat bite fever (Streptobacillus moniliformis) with septicemia in a child. AB - A 5-year-old girl was admitted to hospital with fever, headache and nausea. Her C reactive protein raised from less than 11 mg/l to 65 mg/l and she developed a maculopapular, petechial rash, especially pronounced on the soles and palms. After incubation for 3 days, Streptobacillus moniliformis was found in all blood cultures that had been taken. Some weeks before her admission, the girl had been playing with her grandmother's pet rats, which later had died from an unknown disease. There was no history of rat bite. Her condition improved rapidly after treatment with penicillin and chloramphenicol, and she was discharged from hospital after 10 days without sequelae. PMID- 1411322 TI - First documented case of human babesiosis in Sweden. AB - A 34-year-old splenectomized man presented with fever, myalgia and dysuria. His condition rapidly deteriorated, he became anuric and developed severe haemolytic anaemia, thrombocytopenia and fibrinolysis. Peripheral blood smears revealed intra-erythrocytic parasites consistent with Babesia divergens in 40% of the erythrocytes. The diagnosis was confirmed by gerbil inoculation and by a significant rise in antibody titer. Blood exchange transfusion reduced the number of babesia infected erythrocytes to 1%. Parenteral therapy with a combination of quinine and clindamycin eradicated parasitaemia after 10 days of treatment and the patient rapidly improved. Renal failure necessitated haemodialysis for one month, whereafter the patient made a full recovery. Human babesiosis is a rare disease, but with a potential fatal outcome and should be considered as a diagnostic alternative in splenectomized and otherwise immunocompromised individuals with severe febrile illnesses. PMID- 1411323 TI - Early detection of circulating anodic antigen (CAA) in a case of acute schistosomiasis mansoni with Katayama fever. AB - A 34-year-old male developed acute Katayama fever with fever, diarrhoea, joint pains, headache, urticarial rash and eosinophilia 18 days after falling into and spending 15 min in the water during water-skiing in the outlet of the Volta river. Low anti-schistosomal antibody titres were found by the immunofluorescence assay after 4 weeks, and the first Schistosoma mansoni eggs were found in faeces after 6 weeks. Both symptoms and eosinophilia increased the first days after treatment with oxamniquine, after which he improved gradually. Examination of frozen sera by the newly developed Magnetic Beads Antigen Capture-EIA (MBAC-EIA) later demonstrated a peak in schistosomal circulating anodic antigen (CAA) levels of diagnostic significance already 4 weeks after he was infected. PMID- 1411325 TI - Swedish Association of Urology. Proceedings of the annual spring meeting. Orebro, May 21-22, 1992. Abstracts. PMID- 1411324 TI - Nosocomial pneumonia. PMID- 1411326 TI - The role of the family in psychiatric rehabilitation. AB - This article describes the multiple roles that families can play in the psychiatric rehabilitation process and suggests ways for professionals to collaborate with them. The authors discuss the family's experience of loss and their process of recovery; their caregiving role; their role in supporting other families; their teaching and educational role; their advocacy role; their role as researchers and research subjects; and some suggestions for supporting family roles. PMID- 1411327 TI - Prospective study of psychobiology in first-episode schizophrenia at Hillside Hospital. AB - Heterogeneity has been a consistent problem in the research and treatment of schizophrenia. Despite marked variation in the onset, phenomenology, treatment response and outcome of schizophrenic patients, our ability to identify subtypes is remarkably limited. A major problem in schizophrenia research has been the use of cross-sectional study designs and heterogeneous patient samples at different stages of the illness and who have been previously exposed to neuroleptics which have potentially confounding effects on the disease. This study intends to identify biologic correlates of the phenomenology and course of schizophrenia by using a prospective, longitudinal, repeated measures design assessing biologic and clinical parameters including measures of psychopathology, side effects, and social adjustment to examine clinical variables of treatment response, illness course, and outcome; measures of central nervous system dopamine activity and brain morphology in patients, from the onset of their illness. Patients were ascertained at hospital admission and assessed with a battery of clinical, neuropsychologic, and biologic measures before undergoing standardized treatment for the acute and maintenance phases of the illness. Upon completion, approximately 120 first-episode patients will have entered the study and will have been followed prospectively for up to 5 years and assessed at specific time intervals. Preliminary results reveal significant abnormalities in brain morphology, growth hormone secretion, eye movement function, and psychotogenic response to dopamine agonists in first-episode, treatment-naive patients which are associated with treatment response and outcome. This article describes the study's rationale, design, and methods, and a summary of the published results to date. These are discussed in terms of their significance for putative clinical subtypes and pathophysiological models of schizophrenia. PMID- 1411328 TI - Premorbid and onset features of first-episode schizophrenia. AB - Most descriptive studies of the psychopathology of schizophrenia have focused on the period following illness onset. Little attention has been paid to the assessment of psychopathology before onset of psychotic symptoms. In this study, 71 first-hospitalization patients diagnosed with schizophrenia, schizoaffective, or schizophreniform disorder using DSM-III-R criteria were assessed on measures of premorbid adjustment, clinical history, and presenting symptomatology. A pattern of progressive decline was characteristic of 21 percent of the cases- primarily males with a long-term history of psychotic symptoms before first hospitalization and a trend for more severe negative symptoms at hospital admission. Patients who had a stable pattern of good premorbid adjustment experienced symptom onset and first hospitalization at a later age than those with a chronically poor premorbid adjustment. Time from onset of first psychotic symptom to first hospitalization varied from less than 1 month to over 20 years and was not associated with symptom severity or age of first psychotic symptoms. Systematic characterization of the earliest manifestations of schizophrenia may be important in identifying subgroups of patients with a similar course of illness, and may ultimately facilitate diagnosis, treatment, and understanding of the pathophysiology of schizophrenia. PMID- 1411329 TI - Developmental Processes in Schizophrenic Disorders: longitudinal studies of vulnerability and stress. AB - The Developmental Processes in Schizophrenic Disorders project is a longitudinal study of schizophrenic patients who have recently had a first episode of psychosis. The project focuses on discriminating characteristics of schizophrenic patients that are "stable vulnerability indicators," "mediating vulnerability factors," and "episode indicators" by comparing normal subjects to schizophrenic patients assessed in clinically remitted and psychotic states. A parallel project goal is to identify predictors of relapse, social and work impairment, and illness course among potential psychobiological vulnerability factors and environmental potentiating factors. Hypothesized vulnerability factors and potential environmental stressors are examined first under standardized maintenance antipsychotic medication conditions for at least 1 year. Patients showing stable remission of psychosis after 1 year of maintenance antipsychotic medication are invited to enter drug crossover and withdrawal protocols to determine the need for continuous antipsychotic medication. Vulnerability and stress factors are again assessed. A summary of results to date is presented. Deficits in early components of processing visual arrays and in sustained discrimination of successive ambiguous perceptual inputs are relatively stable across psychotic and clinically remitted states in the schizophrenic patients. Performance on a vigilance task demanding active, working memory also remains abnormal during clinical remission but covaries significantly with psychotic state and is a candidate for a mediating vulnerability factor. Autonomic activation level does not appear to be an enduring vulnerability factor, but it predicts the extent of short-term symptomatic recovery and may mediate the impact of stressors. Under conditions of standardized, injectable antipsychotic medication, independent stressful life events and highly critical attitudes toward the patient in the social environment predict relapse risk. Prospective data suggest that signs and symptoms prodromal to psychotic relapse may be present in about 60 percent of patients. PMID- 1411330 TI - Ventricle-to-brain ratio and symptoms at the onset of first-break schizophrenia. AB - Ventricle-to-brain ratio (VBR) was measured from the computed tomographic (CT) scans of 33 very recent-onset psychotic patients. Illness severity and positive and negative symptoms were also assessed in 21 of these patients with schizophreniform disorder. Forty-five neurology patients served as controls. Analyses revealed no significant differences between the VBR of the psychotic group as a whole, the schizophreniform subgroup, the affective psychotic subgroup, and the controls. Control subjects with a neurological diagnosis of vertigo or syncope had significantly higher VBR than the remainder of the control group and the psychotic group. When the psychotic group was compared to the control group minus those controls with syncope or vertigo, the psychotic group had significantly higher VBR. The schizophreniform subgroup also had significantly higher VBR than the control group minus subjects with vertigo or syncope. In the schizophreniform subgroup, positive symptoms and illness severity were associated with smaller VBR. There was no association between negative symptoms and VBR. PMID- 1411331 TI - Intellectual deficits in first-episode schizophrenia: evidence for progressive deterioration. AB - The developmental processes leading to neuropsychological deficits in schizophrenia are poorly understood. Both early developmental defects and subsequent deterioration may occur. Intelligence test profiles are often used to estimate premorbid ability and deterioration from prior levels of functioning. These characteristics were assessed in samples of first-episode (n = 51) and chronic (n = 50) schizophrenic patients. Although the groups showed few differences on tests to estimate premorbid intellectual ability, the chronic group performed worse on measures considered sensitive to deterioration. Dextral (right-handed) patients tended to have better performance; this effect was marked in the first-episode sample, especially on verbal tests. Male patients showed more evidence of deterioration than female patients. Subgroups differing in the time course of premorbid social dysfunction also differed in intelligence test profiles, suggesting that estimates of social and cognitive deterioration may have concurrent validity. The results support the hypothesis that patients differ in the course of cognitive decline and suggest that deterioration of function may follow the onset of overt psychosis in some patients. Prospective longitudinal studies of first-episode schizophrenic patients could directly test this hypothesis. PMID- 1411332 TI - Phenomenology and functioning in first-episode schizophrenia. AB - One current view of schizophrenia is that its clinical and functional features show a deteriorating course, particularly for negative symptoms. However, this is difficult to study in chronic patients who have been exposed to pharmacologic treatment and institutionalization. Examining first-episode (FE) patients can help clarify which symptoms are present initially and how the symptom pattern is linked to functioning. We evaluated a sample of 37 FE patients with schizophrenia and compared them to 70 other schizophrenia (OS) patients on standard clinical scales, measures of premorbid functioning, and quality of life. FE patients showed a symptom profile similar to OS patients; in particular, there was no evidence that negative symptoms are less severe in the FE group. Analysis of the clinical data led us to the conclusion that the symptom profile of schizophrenia exists at the outset, that negative symptoms are associated with poor premorbid and current functioning, but that the role of positive symptoms is more complex and may vary in subtypes. PMID- 1411333 TI - Generalizability of first-episode studies in schizophrenia. AB - Over a 5-year period, 77 patients in their first episode of psychosis were recruited into a study of autoimmune factors in the pathogenesis of schizophrenia. In this article their demographic and clinical characteristics are compared to those of chronic patients recruited into the same study as well as to the entire outpatient population of a schizophrenia clinic in a Pittsburgh community mental health center. There were no significant demographic differences between the first-episode patients and either of the other groups of schizophrenic patients. There was a significantly higher proportion of black subjects in the clinic population compared to the catchment area from which they were drawn. Clinically, first-episode patients differed from chronic patients in having fewer negative symptoms and more of certain positive symptoms. Age of onset was not significantly different in male and female first-episode cases, although there was a trend of females to be slightly older. We conclude that if diagnosis includes followup and reassessment, findings from research cohorts such as ours can be generalized to populations of outpatient schizophrenic subjects volunteering for treatment. PMID- 1411334 TI - Where are the women in first-episode studies of schizophrenia? AB - Almost all investigations of first-episode schizophrenia uncover more male than female subjects. Two possible explanations for this observation are (1) first episode investigations suffer more or less consistent methodologic biases or (2) the incidence of schizophrenia is higher in men than in women. Data from the markers and predictors of schizophrenia (MAP) project, a community-based first episode study, permitted an investigation of the two alternatives. The results suggest that neither recruitment nor diagnostic vagaries explain the excess of males. Instead, the MAP results, consistent with other recent investigations, suggest that the incidence of schizophrenia is lower in women than in men. The findings are consistent with the literature on gender differences in schizophrenia, which indicates that schizophrenia in women is a less severe disorder than in men. The report includes recommendations for future first episode investigations to ensure adequate representation of women. PMID- 1411335 TI - The Iowa prospective longitudinal study of recent-onset psychoses. AB - In this article, the methods of a prospective longitudinal study of recent-onset psychoses are described. Methodological issues that may be common to studies employing a similar design are discussed in the context of the rationale behind this study's strategies. Particular attention is paid to statistical strategies that maximally exploit longitudinal data. PMID- 1411336 TI - First-episode studies in schizophrenia: criteria and characterization. AB - Studies of early schizophrenia offer several advantages for efforts to unravel the biology, treatment, and outcome of this disorder. A review of available first episode studies, however, suggests marked variability in findings, frequently attributed to the presumed heterogeneity of the disorder. Another cause may be variation in definitions and criteria used. Thus, attention has turned to the study of patients experiencing their first episode of psychosis. Although this strategy will not control for the true underlying heterogeneity of the illness, it provides a valuable method for homogenizing variability due to course. For this strategy to be effective, definition and operationalization of criteria for such studies are crucial. In this article, we reviewed assessment methods used in first-episode studies in the recent literature and found marked inconsistencies. We offer a framework for definition of patient populations for studies of early schizophrenia and outline some key variables that may serve as the basis for fuller characterization of the disorder. It is important to provide data on such variables to enhance comparability among studies of early schizophrenia and to facilitate meaningful interpretation of data. PMID- 1411337 TI - First person account: schizophrenia: some issues. AB - The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Accounts series. We hope that mental health professionals--the Bulletin's primary audience--will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized, and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients, with experiences they believe should be shared, might encourage these patients to submit their articles to First Person Accounts, Division of Clinical Research, NIMH, 5600 Fishers Lane, Rm. 10C-16, Rockville, MD 20857. PMID- 1411338 TI - Stimulation of regeneration of the sciatic nerve by experimentally induced inflammation in rats. AB - The effects of application of a chromic catgut suture (conditioning lesion) placed close to the sciatic or tibial nerves on regeneration of the sciatic nerve after a crush lesion (test lesion), that had been induced after an appropriate conditioning interval (two or four weeks) were assessed. The catgut suture induced an inflammatory reaction around the nerve during the four weeks after application of the catgut suture (conditioning interval) but no signs of degeneration of nerve fibres were seen. There was a significant increase in length of outgrowth of sensory nerve fibres as measured by the pinch reflex test when the test lesion was applied after two and four weeks' exposure to the catgut suture. The rate of regeneration was increased by about 11% when the catgut suture had been applied for four weeks before the test lesion was made. The findings indicate that an inflammatory reaction around a peripheral nerve may act as a conditioning lesion, thereby stimulating regeneration of the nerve. PMID- 1411340 TI - Ischemia in wound healing. II: Design of a flap model--biomechanical properties. AB - A standardized reproducible H-shaped double flap model for biomechanical testing of ischemic wounds was developed in rats. After 10 days of healing all the biomechanical parameters of the flap wounds decreased significantly, compared with normal healing incisional wounds. After 20 days of healing the extensibility as well as the most important biomechanical parameters were still significantly decreased. In part I of this study we showed that on day 1 the blood flow had decreased to 7% of the flow in normal incisional wounds, though it returned to normal on day 16. Here we show that this drop in blood flow results in a significant decrease in all the biomechanical parameters and thereby caused significant delay in the healing of the test wounds. There was no correlation between any of the biomechanical parameters and the length of surface necrosis on the flaps. These necroses thus do not necessarily reflect necrosis of the dermis, where the healing is responsible for the continuity and strength of the skin. PMID- 1411339 TI - Decreased muscle speed, strength and fatigability following two hours of tourniquet-induced ischaemia. AB - Contractile and morphological properties of the rabbit tibialis anterior muscle were measured 48 hours following a two-hour ischaemic episode. Ischaemia was induced using a specially-designed pneumatic tourniquet placed on the rabbit thigh. Maximum tetanic tension of muscle subjected to ischaemia (381 +/- 77 g) was only about 30% of the tension generated by control muscles (1,212 +/- 67 g). The rate of rise of tetanic tension of muscles subjected to ischaemia (15.9 +/- 3 g/ms) was only 33% of control values (44.5 +/- 5.9 g/ms). Muscle fatigue index increased significantly from 0.22 +/- 0.7 in control muscles to 0.55 +/- 0.09 in ischaemic muscles suggesting that muscles subjected to ischaemia had a greater endurance capacity than control muscles. Morphologically, focal necrotic regions and inflammatory cells were observed in ischaemic muscle fibers. Taken together, these data are consistent with selective damage to the fast glycolytic muscle fibers within the ischaemic tibialis anterior muscles. Thus, ischaemia results in overall decreased muscle speed, strength and fatigability. PMID- 1411341 TI - Regenerative response to membranous and enchondral lyophilized allogeneic bone in rabbit skull defects. AB - The regenerative responses of inlays of lyophilized allogeneic bone of membranous (skull) and enchondral (tibia) origin were studied in an experimental cranioplasty model in rabbits. The lyophilized bone particles were also bioassayed for inductive bone production in an orthotopic critical size defect rat model. Three trephined calvarial defects were evaluated in each of 14 adult rabbits. The experimental materials were implanted into two of the defects and the third was left empty for control purposes. The implants disclosed no major structural divergences as assessed by scanning electron microscopy. Healing was evaluated by light microscopy and contact radiography after periods of four and 15 weeks. The lyophilized bone allografts of both embryonic origins displayed a similar fashion of bone regeneration, bone marrow reappearance, and volumetric density of trabecular bone substance and displayed no obvious differences between experimental groups or intervals. The two materials exhibited low osteoinductive potential. PMID- 1411342 TI - Venous anatomy of the thumb and thenar area. AB - The venous anatomy of the thumb and the thenar area, including the first web space, was studied after injection of a polymerizing plastic resin into the vascular tree of six fresh human cadaveric specimens. As in the previously described parts of the hand and fingers, certain anatomical features were consistently present in all examined specimens. The topography of the vessels is different from that of veins in other parts of the hand, and we conclude that this reflects differences in mechanical demands upon the soft tissues in various parts of the hand and the digits. PMID- 1411343 TI - Pharyngo-oesophageal reconstruction with free jejunal transplants. New design of the upper anastomosis to improve monitoring of viability of transfer. AB - Since 1987, 13 free microsurgical jejunal transplants for large pharyngo oesophageal tumors have been done in 12 patients at Tampere University Hospital. The conventional technique was used for the end to end upper anastomosis in seven patients, and our new end to side anastomotic technique in six. Five patients were alive at the time of writing, the mean survival being 22 months (range 1 48). Five patients developed orocutaneous fistulas, three of which healed spontaneously. In the remaining two the fistulas were caused by rapid recurrence of the tumour. There was no significant difference in ability to feed orally or swallow among the patients operated upon by the end to end or the end to side anastomotic technique. Our results show that the free microvascular jejunal transfer is a safe procedure for repair of the hypopharynx. Our new end to side hypopharyngojejunal anastomosis makes it possible to monitor the transplanted bowel reliably by direct vision. PMID- 1411344 TI - Long term evaluation of the unilink anastomotic system. A study with light and scanning electron microscopy. AB - The long term effects of the Unilink mechanical microvascular anastomosis in terms of anastomotic patency and histological changes in the vessel wall were evaluated in 10 rabbits. Both carotid arteries and facial veins were divided and reanastomosed with the Unilink device. At death two years later all 40 anastomoses were fully patent, with histological changes similar to those described previously after 16 weeks, that is, normal endothelial lining, but almost total atrophy of the media at the anastomotic site. The thinning of the vessel wall at the anastomosis caused neither occlusions nor aneurysms during the observation period. PMID- 1411345 TI - Silicone rubber implants for arthrosis of the scaphotrapezial joint. AB - Between 1980 and 1983, 10 patients received high performance silicone rubber condylar implants for the treatment of isolated degenerative changes of the scaphotrapezial joint. Early clinical and radiographic results (at a mean of 15 months) were excellent. Late follow up of these 10 together with a further 11 patients, however, showed migration of the implant and radiological signs of silicone particle synovitis in all but two. We no longer recommend this operation for treatment of isolated arthrosis of the scaphotrapezial joint. PMID- 1411346 TI - Cephalometric measurements in patients with Pierre Robin syndrome and isolated cleft palate. AB - To compare craniofacial structure and growth, two standard lateral cephalograms of 35 children with Pierre Robin syndrome and 30 age and sex matched children with isolated cleft palate were taken at two different ages. The mean (SD) age of the children with Pierre Robin syndrome was 9.5 (3.0) years and of the children with isolated cleft palate 7.1 (1.1) years at the start of the follow up period. The follow up time in the first group was 4.3 (1.6) and in the second group 3.8 (2.7) years. There were no significant differences between the groups in the shape of the cranial base or the maxilla. The main differences were in the mandible, which showed more recession among those with Pierre Robin syndrome. There was a significant correlation between the shape of the maxilla and that of the mandible in that group, but not in the group with isolated cleft palate. During the follow up period there were no significant differences between the two groups in the rate of growth of the jaws. The association between the maxilla and the mandible (ss-n-sm) remained unchanged, or increased, or decreased with equal frequency in both groups. There was no catch up mandibular growth among the children with Pierre Robin syndrome. PMID- 1411347 TI - Clefts with associated anomalies and syndromes in Finland. AB - Probands with clefts born during an 11-year period, 1975-85, were evaluated; 1,586 probands were found of whom 345 (171 males and 174 females, 21.8%) had an associated anomaly. More male patients had cleft lips, with or without cleft palate (CL(P)) and more female patients had cleft palates (CP). The anomalies were subdivided according to anatomical site, and the biggest category was that of the extremities (29.7%) followed by cardiovascular (14.8%) and other facial anomalies (13.0%). The smallest category was chromosomal anomalies (2.7%) followed by miscellaneous anomalies (4.1%). A total of 560 malformations were found. Most anomalies per proband with clefts were found in the bilateral cleft lip and palate subgroup (mean 1.04). The lowest (0.14) was found in the subgroup with the least severe cleft deformity, the cleft lip with or without cleft alveolus. In the CP groups a similar trend was found with 0.21 in the subgroup of submucous cleft palate and 0.33 for the subgroup cleft palate, submucous clefts excluded. A total of 133 probands with 39 different recognised syndromes was delineated, 25 in the CL(P) group and 108 in the CP group (8.4% of the total 1,586 patients with clefts). There was no difference in parental age between probands with an associated anomaly and those with a solitary cleft. Anomalies were more than three times as frequent among probands with clefts as among the general population. PMID- 1411348 TI - Craniofacial development in children with unilateral clefts of the lip, alveolus, and palate treated according to four different regimes. III. The soft tissue profile at 16-18 years of age. AB - The soft tissue profiles of 85 16-18 year old children with unilateral clefts of the lip, alveolus, and palate treated according to four different regimes were studied using lateral skull radiographs. Regimes that included secondary bone grafting to the alveolus in the mixed dentition gave better convexity of the soft tissue profile (excluding the nose) and better soft tissue sagittal jaw relationships compared with treatment regimens that included primary bone grafting. The soft tissue profile in regimes that excluded bone grafting was almost as favourable as those in regimes in which bone grafting was done during the mixed dentition. PMID- 1411349 TI - Reduction mammaplasty. A comparative study of the Orlando and Robbins methods in 292 patients. AB - Between January 1984 and November 1990 a total of 292 patients underwent reduction mammaplasty for hypertrophic breasts. Of these 233 had a superomedial pedicle (Orlando's method) and 36 an inferior pedicle (Robbins' method). Twenty three had various other operations. Those operated on by Orlando's and Robbins' methods were compared retrospectively, and it was found that Robbins' method was superior in younger women because of increased sensitivity, particularly of the nipple-areola complex, and better lactation. In the physician's opinion ugly scars developed in 32% of the patients (n = 287). In our opinion wound closure with a subcuticular suture might improve the quality of the scar. Of the 287 patients assessed, 281 (98%) were satisfied with the physical, and 248 (86%) with the cosmetic, outcome of the operation. PMID- 1411350 TI - The effects of infiltration with adrenaline on blood loss during reduction mammaplasty. AB - Between March and November 1990 a prospective study of the effect of an infiltration of diluted adrenaline on bleeding during and after reduction mammaplasty was carried out in 12 consecutive patients. There was a significant reduction in blood loss to less than 50% of that from the non-infiltrated breasts. There was no signs of increased postoperative bleeding or reduced flap viability as a result of infiltration of adrenaline. PMID- 1411351 TI - The circulation in the nipple-areola complex following subcutaneous mastectomy in breast cancer. AB - To evaluate the decrease in circulation in the nipple-areola complex after subcutaneous mastectomy and immediate implantation of a submuscular prosthesis, the blood flow was studied by both fluorescein flowmetry and laser Doppler flowmetry in 24 patients with invasive breast cancer. In 14 patients a lazy-S shaped horizontal lateral incision was used, and 10 underwent a subcutaneous reduction mammaplasty. After subcutaneous mastectomy with a lazy-S incision there was no significant decrease in blood flow in the nipple-areola complex compared with that in the untreated contralateral breast. In the breasts in which reduction mammaplasty had been done, the blood flow was reduced by 74% as measured by fluorescein (p less than 0.01), and 70% by laser Doppler flowmetry (p less than 0.05), compared with the contralateral breast. Five patients had partial or complete epidermal, and one patient had total dermal, necrosis of the complex, but there was no deep necrosis. No fluorescence was seen within the areas in which necrosis later developed in any of these six cases. The laser Doppler signal in the corresponding areas, however, was not reduced. The results show that the circulation in the nipple-areola complex is reduced more after subcutaneous reduction mammaplasty than after subcutaneous mastectomy with a lazy S incision. PMID- 1411352 TI - Factors that influence the incidence of brachial oedema after treatment of breast cancer. AB - Six factors that may increase the likelihood of swelling of the arm after treatment of breast cancer were investigated in 136 patients who had undergone treatment. The highest incidence of oedema was among patients who had received radiotherapy in high doses with few fractions to the axilla (60%), and in patients with a history of one or more infections in the arm on the operated side (89%). Overweight, oblique surgical incision, infection in the arm, and radiotherapy correlated with arm swelling. The age of the patient and whether the operation had been done on the dominant or non-dominant side correlated less with the incidence of oedema. PMID- 1411353 TI - Comparison of self reported and observed length, width, and colour of scar tissue. AB - To evaluate the reliability of self assessment as a substitute for follow up, 30 self reported assessments of length, width, and colour of abdominal scars were compared with those of clinicians. The degree of disagreement between patients and medical observers was not significant. We conclude that as long as instructions to patients are unambiguous, reliable information may be obtained by postal inquiry. Self reported measurements may thus replace time-consuming follow up visits in studies on the influence of various factors on scar tissue. PMID- 1411354 TI - Basal cell carcinoma in a BCG scar in a young woman. Case report. AB - A 31 year old woman presented with a crusting lesion on the scar of her BCG vaccination. Histological examination showed it to be a basal cell carcinoma, which only rarely arises in vaccination scars, and is particularly unusual in BCG vaccination scars. PMID- 1411355 TI - Multicystic lymphatic malformations of the penis. Report of two cases. AB - Two patients presented with multicystic lymphatic malformations of the penis. These were congenital and progressive, and both were successfully treated by excision after injection of methylene blue. PMID- 1411356 TI - Motoneuron activity and muscle fibre type composition in hemiparesis. AB - The firing of single motor units (MUs) in musculus tibialis anterior (TA) was studied during maximal voluntary effort and maximal speed of walking in 10 patients with severe chronic hemiparesis and the findings compared to normal data. As shown in a previous study, the paralysed TA exhibited an increase in proportion of type 2 fibres as compared with normal muscle. Thus, 57% of the muscle fibres were type 1 and 43% type 2, while the normal percentages were 80% and 20% respectively. The present findings indicate that in the paralysed muscles a little less than half of the fibres, i.e. roughly the equivalent of the type 2 population, was not tonically active either during sustained voluntary contraction or during locomotion. Normally high threshold MUs reached high rates during both modes of activation. The findings paralysed muscles also indicate that a little more than half of the fibres, i.e. roughly the equivalent of the type 1 population, could be brought into tonic firing during voluntary contraction as well as during walking. Their maximal firing rate was, however, no more than two thirds of that of normal low threshold MUs. PMID- 1411357 TI - Gait evaluation in hemiparetic patients using subcutaneous peroneal electrical stimulation. AB - In hemiparetic patients with an implantable peroneal stimulator for correction of drop foot the gait pattern was studied over several years. The gait parameters and M-waves of subcutaneously stimulated muscles were compared with the results obtained before implantation and their variation was observed over time. Of a group of 35 patients with previously implanted electrodes 19 were evaluated. Significant improvements of gait were found although in some cases an excessive eversion of the foot was observed. Nine of these patients had reimplantation because of displacement of the stimulation electrodes after an average time of 3.5 years of proper functioning of the implant. After the reimplantations, similar gait patterns and muscular responses to stimulation were observed as after the initial implantation. PMID- 1411358 TI - Symmetry of electro- and acoustic myographic activity of the lumbar paraspinal muscles in normal adults. AB - The symmetry of paraspinal muscle activity was examined in 15 healthy adults (aged 31-60 years). Acoustic myography (AMG), which provides a measure of force, was recorded with electromyography (EMG) to assess electromechanical relationships during contraction. Bilateral recordings of EMG and AMG were made over the paraspinal muscles at the level of the 4th lumbar vertebra during a fatiguing test manoeuvre. Subjects were strapped to a hinged couch in the prone position. When the upper part of the couch was lowered, subjects maintained the upper body (above the anterior, superior iliac spines) unsupported, in the horizontal position for 60 sec. The EMG and AMG signals were full-wave rectified, integrated (IEMG, IAMG) and recorded on an ink-jet oscillograph during the fatigue test. By 60 sec of activity, IEMG had increased (right 122% +/- 8.7; left 125% +/- 11.8; mean +/- 1 SD as a percentage of initial values) while IAMG (reflecting force) remained unaltered (right 99% +/- 8.2; left 100% +/- 5.3). The IAMG:IEMG ratio (reflecting efficiency of activation) thus declined (right 0.81 +/- 0.08; left 0.80 +/- 0.08). The similarly of changes on both sides of the spine have quantified normal symmetry of paraspinal muscle activity and could be used to assess asymmetry in patients with spinal pathology. PMID- 1411359 TI - Work-related chronic neck impairment. Neck motion analysis in female traverse crane operators. AB - Twenty-one female steel industry traverse crane operators with long-term sick leave (3 (1-8) years) due to chronic neck disability underwent careful analysis of case history, physical status and electrogoniometric three-dimensional recordings of active neck motion. Results were compared with those from working female crane operators having identical work posture and tasks and, further, with a group of working female clerks. The sick-listed crane operators had previous frequent contacts with the primary health care because of complaints from the neck and back. In comparison with the reference groups, the sick-listed crane operators showed tenderness of the trapezius and levator scapulae muscles and a short neck stature in combination with impaired active neck motion range with reduced motion speed. The motion pattern was however unchanged. The findings are consistent with the clinical picture of chronic neck myalgia that persisted despite long-term absence from the previous exposure to high static work load upon the neck-shoulders. PMID- 1411360 TI - Mechanical performance, level of continuous contraction and muscle pain symptoms in home care personnel. AB - The interrelationships between reported complaints, clinical status, mechanical performance and EMG pattern of the shoulder flexors and the knee extensors, respectively, during maximum dynamic contractions were investigated. A group of 97 randomly selected women employed in the home care service participated. Those who reported complaints had more clinical findings, such as reduced mobility, tender points and muscle tightness, than non-complainers. The level of muscle activity during the passive part of the contraction cycle was significantly higher in the shoulder flexors than in the knee extensors. Subjects without reported complaints who had been employed for more than ten years had a significantly lower activity level in the shoulder muscles than subjects without complaints who had been employed for a shorter time. We suggest that a high muscle tension level between contractions might precede muscle pain. A cluster analysis including sociodemographic, clinical and physiological variables revealed different subgroups, which points to the need to investigate the work situation in a multivariate way. PMID- 1411361 TI - Rehabilitation and Parkinson's disease. AB - In this study we evaluated the efficacy of physical therapy together with drug therapy in a group of parkinsonian patients, compared with a group of patients treated using drug therapy only. The physical therapy program lasted four months and included passive and active mobilization exercises, adopted for postural control and equilibrium, walking and prevention of contractures and ankylosis. The assessment was accomplished by means of clinical rating scales and motor performance tests. Patients treated by means of physiotherapy showed an improvement at the end of the study in both clinical scales and motor performance tests. This improvement was noted in both patients with less severe and more severe symptoms as well as in those with shorter and longer disease duration. It is not easy to assess the role played by physical therapy due to the difficulty of an objective evaluation; our results, however, show an improvement in the functional performance of patients and suggest the usefulness of physical therapy associated with drug therapy in a comprehensive treatment for Parkinson's disease. PMID- 1411362 TI - Clues to cancer etiology from studies of farmers. AB - This article summarizes cancer risks among farmers to clarify the magnitude of the problem and to suggest directions for future research. Significant excesses occurred for Hodgkin's disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin's lymphoma and cancers of connective tissue and brain. These excesses occurred against a background of substantial deficits among farmers for total mortality and mortality from many specific diseases. The tumors vary in frequency, histology, and prognosis and do not fall into any obvious grouping. Two commonalities may be important. Several of the tumors excessive among farmers appear to be rising in the general population and are excessive among patients with naturally occurring or medically induced immunodeficiencies. Therefore epidemiologic studies on specific exposures among farmers may help explain the rising trend of certain cancers in developed countries and provide clues to mechanisms of action for environmental carcinogens. PMID- 1411363 TI - Cancer incidence and mortality among Swedish Baltic Sea fishermen. AB - A 25% lower cancer mortality was found for 1360 Swedish fishermen who fished on the Baltic Sea than for the general population. The fishermen consumed twice as much fish as the population in the same county. In spite of the low overall cancer mortality, increased mortality from myeloma, as well as increased incidences of gastric carcinoma and squamous cell cancer of the skin and lips, was observed in the cohort. The decrease in risk for ischemic heart disease was not significant. Whether the dietary intake of fatty acids and selenium from fish contributed to the decreased risk was difficult to evaluate. Moreover, whether the consumption of fish from the Baltic Sea, contaminated with, for example, polychlorinated dioxins and dibenzofurans and other persistent organochlorine substances, contributed to the observed increased specific cancer risks is not known. However, the net health effect of high fish consumption from the Baltic Sea seems to be positive. PMID- 1411364 TI - Occupational exposure to sulfuric acid in southern Ontario, Canada, in association with laryngeal cancer. AB - A case-referent study, designed to test associations between asbestos, nickel, and the development of laryngeal cancer, was conducted in southern Ontario in 1977-1979. The cases were individually matched to neighborhood referents for gender and age. This constituted the primary study. Personal interviews had secured tobacco, alcohol, and detailed work histories. To 183 of the male pairs was added retrospective assessments of sulfuric acid exposure for each job, blind of disease status; this constituted the data base for an augmented secondary analysis. Logistic regression revealed statistically significant odds ratios when tobacco and alcohol were controlled. Exposure-response gradients were strongly positive with odds ratios in the range of 1.97 [95% confidence interval (95% CI) 0.63-6.13] for short duration-low level exposure through 6.91 [95% CI 2.20-21.74] for long duration-higher level exposure employing progressively more specific definitions of exposure. Asbestos as a confounder and the interaction terms examined were nonsignificant. These findings are corroborative of those of other studies. PMID- 1411365 TI - Empirical assessment of the effect of different summary worklife exposure measures on the estimation of risk in case-referent studies of occupational cancer. AB - The effect of different summary measures of worklife exposure on the estimation of risk is reported. Two matched case-referent studies associating sulfuric acid exposure and cancer from Baton Rouge and southern Ontario were used. Five summary exposure measures were converted to discrete levels of exposure through the selection of equivalent percentile points on each measure's respective percentage frequency distribution for logistic regression modeling purposes. The southern Ontario data set exhibited only minor differences across all five exposure measures. The Baton Rouge data set, however, produced different results, and the time-dependent measures appeared to underestimate risk. It is possible, therefore, to obtain different estimates of risk depending on the exposure measure selected. It is recommended that, in the absence of proved models for assessing exposure, a variety of summary measures be used to estimate risk. This approach would facilitate the comparison of findings across studies. PMID- 1411366 TI - An apparently incongruous exposure-response relationship resulting from the use of job description to assess magnetic field exposure. AB - Empirical data are presented to support the observation that nondifferential misclassification of subjects classified according to an ordinal scale can result in an artifactual nonmonotonic exposure-response curve. This phenomenon can be interpreted erroneously as an indication that an observed relationship is not causal. The occupational exposure of 40 subjects to extremely low-frequency magnetic fields was estimated on the basis of their job description while their "true" exposure was determined by direct dosimetry. A "true" risk was assumed to exist, and estimates of risk that could be obtained through hypothetical case referent or cohort studies were calculated. PMID- 1411367 TI - Agreement on medical fitness for a job. AB - Five experienced occupational physicians independently reviewed the uniformly structured, concise records of 180 applicants who had applied for a job in one of three categories. All had undergone a preemployment medical examination by the Governmental Occupational Health and Safety Service. Agreement was assessed by calculating the percentage of disagreement and Cohen's kappa. Agreement between the five panel physicians and between the panel physicians and the Service appeared to be poor, with overall percentages of disagreement of 31 and 37%, respectively, and kappa values of 0.38 and 0.37, respectively. On the average 31% of the applicants judged as unfit by one physician had been assessed as fit by the others, whereas agreement was only marginally better when detailed medical criteria for fitness were available. Lack of consensus on the medical fitness of an applicant, as evidenced by this study, suggests that the validity of such a judgment may be questionable even when detailed fitness criteria are available. PMID- 1411368 TI - Lack of renal changes in stainless steel welders exposed to chromium and nickel. AB - Biochemical markers of kidney damage were examined in 52 male stainless steel welders (manual metal arc welding) exposed to chromium and nickel. No difference was found in the mean urinary excretion of total proteins, albumin, protein 1, transferrin, retinol-binding protein, lactate dehydrogenase, lysozyme, or beta-N acetylglucosaminidase in a comparison with matched referents. Beta 2 microglobulin was slightly increased in those welders with a urinary chromium concentration of greater than 64.5 nmol.mmol-1 creatinine. The prevalences of abnormal values did not differ from those observed in the reference group. No correlation was found between the concentrations of chromium or nickel in urine and that of proteins or enzymes. No consistent or clinically significant renal impairment was revealed among the stainless steel welders exposed to a chromium air concentration slightly above the current threshold limit value of the American Conference of Governmental Industrial Hygienists for water-soluble hexavalent chromium compounds (50 micrograms.m-3). PMID- 1411369 TI - Seasonal variation in neck and shoulder symptoms. AB - The objective of the investigation was to study the course of neck and shoulder symptoms and the predictors for these symptoms among women in light sedentary work. Postal surveys were conducted among 351 tellers (age 20-50 years) of a bank company in September, December, March, and May. The response rates were 74-90%. The outcome was the frequency of the symptoms during the previous three months. In the analysis, univariate explorations and random-effects logistic binomial regression for distinguishable responses were used. A change in the frequency of neck and shoulder symptoms was seen in 40.5% of the subjects during the follow-up period from autumn to spring. The frequency of the symptoms decreased from autumn and winter towards spring. The stability of the frequency of the symptoms was positively associated with age. Seasonal variation in symptoms should be considered when preventive programs against neck and shoulder disorders are planned and evaluated. PMID- 1411370 TI - Electromyographic signs of shoulder muscle fatigue in repetitive arm work paced by the Methods-Time Measurement system. AB - Surface electromyographic (EMG) recordings from the lateral and cervical portions of the descending trapezius muscle and from the infraspinatus muscle were assessed for six female subjects performing a standardized repetitive work simulation task for 1 h. The work pace was determined according to the Methods Time Measurement system to 2466 cycles.h-1. The variation in load levels were high and indicated dynamic muscle activity. A decrease in the EMG mean power frequency and an increase in the root-mean-square amplitudes, both indicating muscle fatigue, developed in all muscles of most of the subjects. EMG signs of fatigue, analyzed separately for each 5-min period, showed variable fatigue patterns both between muscles and between subjects. It is therefore suggested that dynamic work movements do not protect the muscles of the shoulder and neck from fatiguing processes in highly repetitive work with short cycle times. PMID- 1411371 TI - Screening for occupational cancer. AB - The main strategy for preventing occupational cancer is an environmentally based approach or primary prevention. However, it should be combined with screening, early diagnosis, and treatment. This review discusses screening for occupational cancer but not from the point of view of medical screening. Instead it focuses on asbestos exposure and asbestos-related cancer in Finland and the role screening plays in the current Finnish asbestos program. For example it is the feeling in Finland that screening is a very effective way of preventing further occupational exposure to asbestos and of organizing antismoking campaigns. An individually oriented strategy in cancer prevention should include the modification of exposures by behavioral change, the monitoring of early effects of exposures, and health examinations. The termination of exposure, antismoking campaigns, improved diagnostics, and careful attention to compensation issues combined with the study of other opportunities for prevention are seen as the key issues in screening. PMID- 1411372 TI - Workplace cancer prevention. AB - Safety and health matters should be an integral part of the decision making of management. Cancer prevention at the workplace requires cooperation between management, occupational health personnel, and workers. At the planning stage of a new production facility the safety and health personnel should actively participate and bring their experience and special knowledge to the planning process. The basis for cancer prevention is exact information about exposure and real risk levels. Modern technology can essentially minimize both exposure and health hazards. PMID- 1411373 TI - Carcinogen metabolism and individual susceptibility. AB - Many chemical carcinogens need activation by drug metabolizing enzymes, principally cytochrome P450 enzymes, to become capable of binding to deoxyribonucleic acid and initiating the carcinogenic process. The activity and inducibility of drug metabolizing enzymes are regulated by interplay between genetic, host, and environmental factors. Consequently, individual differences in cancer susceptibility might be explained somewhat by genetic differences in metabolic activation. Three examples, the induction of aryl hydrocarbon (benzo[a]pyrene) hydroxylase by polycyclic aromatic hydrocarbons, polymorphic debrisoquine/sparteine oxidation, and polymorphic acetylation, are briefly reviewed. Despite useful animal models and promising early human findings, no consensus has been reached about the significance of genetically based differences in drug metabolism in cancer etiology. It is expected that, with the use of molecular biological methods, the genetic background of study subjects can be investigated without bias caused by the disease, age, treatment, or other factors which have plagued investigations thus far. PMID- 1411374 TI - Analysis of deoxyribonucleic acid adducts in workers. AB - Repeated blood samples were obtained from volunteers who were occupationally exposed to polycyclic aromatic hydrocarbons in a Finnish iron foundry. Aromatic adducts were determined in white blood cell deoxyribonucleic acid of the subjects with the 32P-postlabeling technique after nuclease P1 treatment and butanol extraction, which showed no major difference. When repeated samples were analyzed, it appeared that the oldest ones displayed the lowest adduct levels, probably due to the instability of the adducts upon storage at -20 degrees C. The workers tended to maintain their adducts at a uniform level, a finding suggesting the contribution of host factors in the control of adduct levels. PMID- 1411375 TI - Design strategies, results and evaluations of long-term chemical carcinogenesis studies. AB - Long-term toxicology and chemical carcinogenesis experiments typically involve both sexes of two species of rodents divided randomly into sets of 50-60 animals per control and exposure groups. Ordinarily three exposure concentrations are gradated down from a top level likely to show some chemically associated toxicity, but which should not compromise the normal well-being or growth and survival patterns of the animals unduly. Duration of exposure is generally two years. Single, intermittent, or varied exposures are used to mimic specific occupational or environmental situations. Exposures are started prior to conception, during gestation and lactation, or at specified times thereafter. Extensive gross observations and microscopic pathology are performed on each animal, and incidences of neoplastic and nonneoplastic lesions are evaluated in age-adjusted statistical comparisons. The collated findings are then interpreted, evaluated, and presented for scientific peer review in public meetings, the aim being to identify qualitatively those environmental and occupational exposures that may likely induce cancer in humans. PMID- 1411376 TI - Use of molecular biology techniques in cancer epidemiology. AB - Biochemical techniques have been applied for years in clinical medicine to unravel disease indicators and mechanisms. The study design, resembling that of a case-referent study, has been to compare diseased and healthy individuals. Conclusive results have been obtained for diseases in which relatively few factors cause high risks. The same study design has been maintained with sophisticated methods of molecular biology, which have revealed many types of deoxyribonucleic acid lesions associated with cancer. It is likely that the relatively simple cross-sectional and case-referent studies require input from epidemiologists to unravel multifactorial etiologies. Longitudinal approaches may be the only alternative with which to evaluate the role and usefulness of the application of molecular biology markers in studies of cancer. PMID- 1411377 TI - The molecular epidemiology of oncoproteins. AB - Oncogene activation, which appears to play a critical role in carcinogenesis, can be conveniently studied in biological samples via immunologic detection of oncoprotein products with monoclonal antibodies. Immunohistochemical and immunocytochemical detection of oncoproteins can be used to differentiate normal cells from cancer cells, including those of cancers of occupational concern such as lung, bladder, and liver. Furthermore, oncoproteins appear to reach the extracellular environment and are detectable with immunoblotting techniques in the urine and serum of cancer patients. Similar techniques applied to the screening of sera of occupational cohorts with carcinogen exposures indicate that oncoproteins can be detected in workers at increased risk of the development of cancer, and thus oncoprotein detection may be a useful molecular epidemiologic biomarker of preclinical response for the surveillance and prevention of occupational cancer. PMID- 1411378 TI - Occupational cancer and carcinogenesis. PMID- 1411379 TI - Exposure from occupational versus other sources. AB - There is an increasing need to consider the various routes of exposure to individuals in occupational settings, as well as the exposure of the general public to a broad spectrum of carcinogens. The need to consider indoor environments is increasingly recognized in light of the amount of time spent indoors by a large majority of the population and the recognition that levels of certain toxicants are higher indoors than outdoors. This overview highlights (i) a general comparison of exposure to indoor and outdoor levels of 12 volatile organic compounds and (ii) the exposure of workers and the general public to benzene, 1,3-butadiene, formaldehyde, styrene, tetrachloroethylene, phthalate esters, polychlorinated dibenzofurans, radon, and electromagnetic fields. PMID- 1411380 TI - Cancer morbidity by occupation. AB - Data on cancer morbidity by occupation are available from surveillance systems, such as linkage studies based on census data and cancer register data. These data serve various purposes. First, they show the social distributions of cancer diseases. Second, they can form the background for generating hypotheses about chemical carcinogens by identifying occupations at high risk of cancer. Third, cancer morbidity data can be used in the interpretation of results from hypothesis-testing studies. Fourth, the data can facilitate the identification of cancer risks associated with new technologies and way of life in the service society. Finally, the data can be considered for inference about future trends in cancer mortality. Data from the Danish occupational cancer study are used for illustration. PMID- 1411381 TI - Proposal for future uses in epidemiology for cohort studies on the prevention of work-related cancer. AB - A new use of the cohort method in cancer prevention is proposed involving individual collection of information on past exposure to dominating cancer determinants. It is assumed that it is possible to determine individual cancer risk and, subsequently, to estimate the individual risks of cause-specific cancers on the basis of accurate individual data on exposure to cancer determinants. Individuals at given risk levels should subsequently be assigned to defined risk categories to establish groups designed for risk-determined screening programs and risk-determined information intervention. As increased risk to work-related cancer is generally more strongly related to past than to current exposure, a large proportion of those who are at high risk are no longer employed and thus not in reach of occupational health physicians. Therefore, risk determined intervention should be integrated into the daily work routines of both occupational health physicians and primary care physicians. PMID- 1411382 TI - Identification of carcinogens within the IARC monograph program. AB - Fewer than 50 chemicals, groups of chemicals, or mixtures have been causally linked with cancer in humans. Some 250 chemicals have, however, been found to be carcinogenic to rodents. Carcinogenic risk factors that have been identified for humans occur in clearly quantifiable exposure situations, but epidemiologic information on cancer in humans is missing or inadequate for the great majority of chemicals. Extrapolation of animal data to humans is complicated because long term carcinogenicity studies on animals are carried out under simplified conditions, whereas humans are exposed to a multitude of exogenous and endogenous agents. Furthermore, the carcinogenic process includes multistage and multifactorial aspects, and human populations are genetically and physiologically heterogeneous. Although the science of carcinogenesis is making rapid progress in terms of understanding some of these processes and interactions, there is still a need to err on the side of safety and accept animal data as a warning signal for possible human effects. PMID- 1411383 TI - A historical perspective on the classification developed and used for chemical carcinogens by the National Toxicology Program during 1983-1992. AB - To evaluate, interpret, and better communicate the data and findings from long term chemical carcinogenesis studies on laboratory animals, the National Toxicology Program began using five categories or levels of evidence of carcinogenicity in 1983 (clear, some, equivocal, and no evidence and inadequate experiment). Through July 1991 these defined terms had been used to describe 144 chemical carcinogenesis studies comprising 530 sex-species experiments. Together with a selected descriptor of the chemically associated level of evidence for each experimental unit (male rats, female rats, male mice, female mice), mention is made of the length of the experiment, route of exposure, and the particular tumor type or types for each organ or system affected. The scientific judgements are comprised of this relevant information to inform the readers and users of these evaluations. In this paper the background rationale for the development and proper use of these categories of evidence of carcinogenicity are detailed, together with some personal reflections. PMID- 1411384 TI - Perspective and overview of the concepts and value of hazard identification as the initial phase of risk assessment for cancer and human health. AB - The identification of potential human health hazards stems from the obvious need to prevent, avoid, reduce, and eliminate exposure to hazardous agents, mixtures of agents, or exposure circumstances. The first step in the risk assessment process centers on determining if a hazard exists. The following strategies are used for this purpose: (i) epidemiologic investigations, (ii) long-term chemical toxicology and carcinogenesis studies on laboratory animals, (ii) shorter-term in vivo and in vitro assays, and (iv) physicochemical structure-activity relationships. Indicator 1 is the most relevant and reliable if adequate data are available; indicator 2 is the most valid and useful alternative for human experience; indicator 3 allows certain toxicologic end points to be identified, but generally needs confirmatory and supportive information; and indicator 4 has made gains in the area of predictivity. The advantages and limitations of each are given. The magnitude of the overall cancer hazard identification effort and a likelihood number of eventual chemical carcinogens have also been estimated. PMID- 1411385 TI - Quantitative assessment of human cancer risk. AB - Because exposure to carcinogens cannot be eliminated, it has become important to define exposure levels which are acceptable to society or are irreducible. Quantitative assessment of cancer risk is part of this process. This paper presents a definition of risk and discusses the role of epidemiologic observation in the quantitative assessment of cancer risk, the estimation of risk from epidemiologic data, and the role of animal cancer bioassays in the quantitative assessment of cancer risk. It is emphasized that quantitative risk assessment is inevitably based on multiple assumptions. Where possible, the magnitude of errors associated with these assumptions should be stated, even to the extent of an acknowledgment of complete ignorance. PMID- 1411386 TI - Technological changes in cancer prevention. AB - Exposures and technologies in the workplace are changing due to a variety of factors, including newly developed technologies, mechanization and automation, and improvements in industrial hygiene primarily effected in many developed countries. In addition substitution and removal of carcinogenic constituents in the workplace and general environment are increasing in a number of instances, particularly in North America, Western Europe, and Japan, and they are being accompanied as well by remediation either by source reduction, recycling, or compliance to more stringent national and international regulations and standards. This overview highlights some of the strategies employed in the technological changes in cancer prevention and cites examples in source reduction, changes in formulation, product or process changes, recycling, and hazardous materials management. PMID- 1411387 TI - [Treatment of movement disorders using botulinum toxin]. AB - Intramuscular injections of botulinum toxin (Botox) are followed by a dose dependent focal paresis which can be used to treat several focal movement disorders. Botox injections are recommended as effective for the treatment of blepharospasm, hemifacial spasm, and cervical dystonia (torticollis). Focal dystonias elsewhere (for example, writer's cramp) can often be treated with similar success. Others, such as oromandibular dystonia, are more difficult to treat. In the case of more generalized dystonias, some focal muscle spasms can be treated with success by local intramuscular injections. New indications are still being investigated, for example in focal tremors and spasticity. Side effects are in general slight and disappear at the end of toxin effect. In general, it is necessary to repeat the injections after a couple of months, due to a cessation of effect after regrowth of nerve terminals. New injections have similar effects even over years of treatment. PMID- 1411388 TI - [Diagnostic value of ambulatory daily blood pressure profile: comparison with measurements performed by a laboratory technician]. AB - Office blood pressure measured by a physician is often higher than under the usual ambulatory conditions. Therefore, alternative methods such as self assessment of blood pressure and ambulatory blood pressure measurements are increasingly promoted. The purposes of this study, covering 613 referred patients, were (1) compare office blood pressure with continuous ambulatory blood pressure measurements, (2) compare office blood pressure with blood pressure values recorded by a trained technician in the absence of a physician and (3) analyze the interpretation of the blood pressure profiles by the referring physicians. Office blood pressure exceeded average ambulatory blood pressure in 94% of the patients and also the blood pressure values recorded by a technician in 88%. According to the office blood pressure there were 523 patients with elevated blood pressure, 20 with isolated increased systolic blood pressure and 70 with normal blood pressure. Office blood pressure was higher (systolic +17 +/- 18 and diastolic +9 +/- 12 mm Hg, p less than 0.0001) than the average value of the ambulatory blood pressure profile, whereas the latter did not differ significantly from blood pressure values measured by the technician (systolic -1 +/- 12 and diastolic -2 +/- 9 mm Hg). 190 of the 523 (36%) patients had white coat hypertension according to the ambulatory blood pressure measurements. Conventional blood pressure measurements by the technician yielded a high sensitivity (84%) and specificity (87%) for distinguishing white coat hypertension. Analysis of the questionnaires showed that opinions about normal limits of ambulatory blood pressure vary considerably.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411390 TI - [Acute alveolitis due to mesalazine]. AB - A 66-year-old male developed lymphocytic alveolitis with bronchiolitis after 3 month's treatment with mesalazin for ulcerative colitis. The patient's symptoms disappeared after halting mesalazin and increasing the steroid dose, the reduced diffusing capacity ameliorated and the thoracic X-ray normalized. The question whether this was a case of pulmonary involvement in inflammatory bowel disease or a drug side effect. PMID- 1411389 TI - [Cost-benefit analysis of a new treatment concept in patients with indwelling catheters]. AB - An earlier and a new treatment concept for patients equipped with long-term indwelling bladder catheters were compared with regard to cost, expenditure of time, and equipment in a retrospective study involving 58 patients treated by the earlier concept and 60 treated by the new one. The new concept dispensed with the need for bladder irrigation and routine replacement of the indwelling catheters. Under the earlier concept, 18 indwelling catheter replacements and 53 bladder irrigations were required per patient and year during the years 1979/80. This compares with 6 indwelling catheter replacements and 0.05 bladder irrigations per patient and year for the years 1989/90 under the new concept. The use of analgesics and spasmolytics fell from 55 to 21 units per patient per year. Significantly fewer urinalyses were performed during 1989/90. The use of antibiotics remained unchanged. When compared with the earlier one, the new concept for the management of patients with indwelling catheters provides savings of 1265 minutes (21 hours) of nursing time and sFr. 405 for equipment per patient per year. Applied to our geriatric hospital (120 beds, 80 nursing staff), this translates into annual savings of one full nursing post and sFr. 34,000 for equipment. PMID- 1411392 TI - [Respiratory rehabilitation]. AB - Pulmonary rehabilitation is directed at all patients with severe chronic respiratory insufficiency of any origin. Patients with chronic obstructive pulmonary disease clearly represent the majority. In a pulmonary rehabilitation programme, the patient must gain a better understanding of his disease and of the goals of the treatment. He benefits from permanent teaching on methods of independent self-treatment and follows a regular programme of exercise training and nutritional support aimed at increasing effort capacity. The ultimate goal of the programme is to send the patient home with improved quality of life and a higher degree of independence. PMID- 1411391 TI - [Leiomyosarcoma of the breast 16 years following successful treatment of a rhabdomyosarcoma of the orbit in childhood]. AB - A case of a mammary leiomyosarcoma in a 23-year-old woman is presented. The tumor appeared 16 years after successful treatment of an embryonal rhabdomyosarcoma of the orbit. Rhabdomyosarcomas are the most frequent soft tissue tumors of childhood, the orbit and the paratesticular region being the most common primary site for this tumor. In contrast, leiomyosarcomas other than those evolving from the viscera or the urogenital organs are rare neoplasms at any age. With the improvement of cancer treatment and survival rates, the risk of late effects after successful treatment for malignant tumors during childhood is increasing. Growth, development and fertility may be impaired and cosmetically disturbing facial and dental complications are common. Development of novel primary tumors is a known further consequence of successful treatment of brain tumors, retinoblastoma and acute leukemias. This is the case when high dose local radiation therapy and/or chemotherapy, especially alkylating agents, were used. Development of novel primary tumors is also known after treatment of childhood rhabdomyosarcomas. This report is intended to show that a second primary tumor may occur many years after a first successfully treated malignant neoplasm, and that young people are at risk for development of tumors at sites that are uncommon to this age group. PMID- 1411393 TI - [Staging and prognosis of colorectal carcinoma]. AB - Three different systems in staging colorectal cancer (TNM3, ACPS, TNM4/Dukes) have been compared in 318 patients treated at some stage of their disease at Berne University Hospital. Simultaneously, the role of some prognostic factors for survival and relapse has been analyzed. The estimated 5 years' survival rate for all patients is 42%. After complete removal of the tumor 49% of patients relapsed. In a multivariate analysis the stage, age above 80 years and the site of the primary tumor have an influence on survival and relapse. Blood transfusions had no effect on either in this analysis. The concordance of the three staging systems is good and the resultant survival curves are similar. TNM3 puts some patients with a bad prognosis into stage I. ACPS classifies patients with residual tumor after surgery with patients with distal metastasis. It has no further advantages over TNM4. TNM4 seems at present to be the best staging system. It incorporates the advantages of the well-known Dukes classification and, with possible refinements, has the qualities to be used as a standard method. PMID- 1411394 TI - [Pulmonary changes in ulcerative colitis]. AB - We report on a 54-year-old patient who developed symptoms of bronchitis 3 months after colectomy for ulcerative colitis. Bronchiectases were documented by high resolution computer lung scan. Several cases of ulcerative colitis associated with alterations of the airways, of the pulmonary parenchyma, of the lung vessels and of the pleura have been published. Symptoms of bronchitis, often on the basis of bronchiectases, are the most commonly observed pulmonary problems in this inflammatory bowel disease. Furthermore, abnormal pulmonary functions have been found even in asymptomatic patients. Our patient was treated with oral and topical corticosteroids. The symptoms disappeared and pulmonary function returned to normal. PMID- 1411395 TI - [Improved glucose regulation and microalbuminuria/proteinuria in diabetic patients treated with ACE inhibitors. A meta-analysis of published studies of 1985-1990]. AB - In patients with diabetes mellitus, metabolic control, hypertension and kidney function are important prognostic factors. In this respect ACE inhibitors exhibit, according to previous publications, a potentially beneficial effect on diabetic patients. To further clarify this effect of ACE inhibitors, a meta analysis of 21 studies of type I and II diabetics under therapy with ACE inhibitors was performed. Altogether 325 cases were analyzed. The duration of diabetes varied between 2.5 and 22 years. Therapy with ACE inhibitors under long term treatment (up to 12 months) reduced diastolic blood pressure (-25%) and, both for type I and II diabetics, fasting blood sugar (-14%) and HbA1 (-9%). Microalbuminuria/proteinuria was reduced by 33% under short-term treatment with ACE inhibitors (up to 3 months) and by 66% under long-term treatment. Analysis of the subgroups with microalbuminuria (30-300 mg/day, n = 48) or clinical proteinuria (greater than 300-1500 mg/day, n = 9) showed similar results. The outcome of this meta-analysis shows that the treatment of diabetic patients with ACE inhibitors not only effectively reduces high blood pressure but also reduces microalbuminuria/proteinuria and, in addition, exhibits an anti-hyperglycemic effect by improving blood sugar levels. PMID- 1411396 TI - [Current aspects in the diagnosis and therapy of narcolepsy]. AB - Narcolepsy is a potentially invalidating disorder of the sleep and wakefulness structure, characterized by attacks of sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed night sleep. The diagnosis is mainly based on the history. Additional sophisticated examinations, such as nocturnal polysomnography, are primarily indicated to rule out other causes of excessive daytime somnolence. The recently detected high correlation between a certain HLA status and cataplexy has led to new pathogenetic concepts. The primary aim of the therapy is to keep the patient at work rather than attempting a symptom free state. Measures to organize his day with planned naps should precede the use of medication. Besides stimulants against daytime somnolence and tricyclic antidepressants to suppress cataplectic attacks, some new drugs have been administered successfully against the various symptoms of narcolepsy in recent years. PMID- 1411397 TI - [Measurement of pulmonary artery occlusion (wedge) pressure using the Swan-Ganz catheter: various pitfalls]. AB - The Swan Ganz pulmonary artery catheter is widely used in the intensive care unit. It allows the determination of important hemodynamic parameters. Among these, pulmonary artery occlusion pressure ("wedge" pressure) is often considered to reflect accurately left ventricular preload and pulmonary capillary hydrostatic pressure. However, many interferences may render data interpretation difficult, especially in patients undergoing mechanical ventilation. This article reviews some of these pitfalls. PMID- 1411398 TI - [Eosinophilic colitis--an unusual cause of acute abdomen. Case report and literature review]. AB - Eosinophilic gastroenteritis (EGE) is an etiologically obscure and rare inflammation which can affect all sections of the gastrointestinal tract from esophagus to rectum in a diffuse or segmentary manner. An infiltrate of eosinophilic granulocytes is found to varying degrees in all wall layers. The clinical symptoms depend on the site and extent of organ involvement. Diagnosis can only be established histologically. Peripheral eosinophilia is inconsistent and not diagnostic. ESR, leukocyte count, serum IgE, and RAST tests in foodstuffs may be normal or elevated. Two women patients are described with tumorous eosinophilic colitis of the cecum and colon ascendens, who underwent surgery for clinical acute abdomen. A further woman patient was hospitalized with bloody diarrhea and marked eosinophilia in the blood findings. Eosinophilic colitis was likewise found histologically in the mucosa which appeared with reddened patches in sigmoidoscopy. Eosinophilic colitis associated with eosinophilic gastroenteritis is rather rare and may therefore be overlooked. Our literature review contains only 64 such cases, in only 6 of which was the tumorous form found. Counting our own patients as well, eosinophilic colitis occurs somewhat more frequently in women (27 = 56%) than in men (21 = 44%). The clinical symptoms, possible causes and therapeutic approaches are discussed in the light of the literature. PMID- 1411399 TI - [Spontaneous reporting system for the assessment of new, unknown and rare undesirable effects of drugs]. AB - The Swiss Drug Monitoring Center SANZ operates the spontaneous reporting system in Switzerland. Spontaneous reporting schemes represent the systematic approach to the collection of individual case reports on suspected adverse drug reactions (ADR). ADR spontaneous reporting systems are an important component of the postmarketing surveillance of drugs. Spontaneous reporting systems are primarily designed to detect new and unexpected ADR; they generate signals about possible ADR and create hypotheses to be tested in pharmaco-epidemiological studies. Besides collecting, analyzing and evaluating single case reports it is important to extract those cases from the data pool which can be used to produce signals. A computer-assisted early warning system enables SANZ to detect cases with signal function and thus to track down new, rare and unexpected ADR. Carefully selected parameters can help to identify important new hazards. However, the detection of new and unexpected ADR depends to a large extent on the minds of alert physicians and the practicing clinician's awareness of and cooperation with ADR reporting. PMID- 1411400 TI - [Decrease in general health status, febrile state and sinusitis in renal insufficiency]. AB - A 59-year old man, dialysed for 9 years because of chronic renal failure of unknown etiology, was also suffering from a hypertensive cardiopathy and anemia. He has received more than 70 units of blood over the past few years. An elevated blood aluminium level prompted treatment with desferrioxamine for 3 years. Following episodes of melena, an intestinal-wall lesion, located 8 cm above the ileo-caecal valve was discovered. Blood serotonin levels were elevated; biopsy of the liver revealed tumor cells with round-shaped nuclei which stained positive for synaptophysin, findings compatible with a carcinoid tumor or a pancreatic islet-cells tumor. Considering the whole clinical situation, aggressive diagnostic of therapeutic measures were not pursued any further. The patient lost 8 kg over the next few months and was finally hospitalised with fever. Physical examination revealed ascites, edema and a gingival abscess which was drained. Blood cultures grew Klebsiella pneumoniae. Antibiotics were prescribed. A month later the patient complained again of fever accompanied by myalgias, edema and pain of the eyelids, mainly on the right side, pain in the maxillary area and on right eye motion. ENT examination revealed a necrotic lesion of the right middle turbinate which on histology was diagnosed as acute purulent rhinitis without granuloma or vasculitis. A CT-scan demonstrated mucosal thickening of the left sphenoidal, ethmoidal, frontal and maxillary sinuses without any osteolytic lesions. The patient suffered a sudden right eye blindness with signs of retinal ischemia accompanied by an elevated sedimentation rate of 130 mm. Steroid treatment for suspicion of a temporal arteritis was introduced. 2 days later the patient was rehospitalized in a semi-comatose condition. No new information was gained from the usual laboratory investigations and the physical examination was comparable to the previous hospital stay. Blood cultures remained sterile. He died a few hours later. DISCUSSION: The discussant, A. de Torrente MD, accepts the diagnosis of a hypertensive cardiopathy, renal failure of unknown origin and a carcinoid of the terminal ileum with hepatic metastases. The role of iron overload as a contributory factor for the cardiac disease is discussed. More problematic are the manifestations of the terminal disease with involvement of the sinuses, the eyes and the mouth. The "lethal midline granuloma" (a syndrome and not a disease entity) covers many different diseases which can be considered in this case: Wegener's granuloma, various lymphomas, parasitic, bacteria- and fungus-induced diseases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1411401 TI - [The status of surgery in 1992 or: what is the future of visceral surgery?]. PMID- 1411402 TI - [Hepatitis and HIV infection in users of illegal drugs]. AB - The prevalence of markers for ongoing or past infections with the hepatitis viruses A (HAV), B (HBV), D (HDV) and C (HCV) and with HIV are analyzed in i.v. drug users. The relevant serological parameters were measured in 1989, 1990 and 1991 in 220 to 380 sera each of drug users who frequented the open drugscene "Platzspitz" in a recreational area in the center of Zurich. The prevalence of viral markers for ongoing and past infections was many times higher in drug users than in the Swiss population. Over the three years the prevalence of HAV-markers rose from 50% to 72%, remained stable for HBV (52%, 57%, 58%) and most probably also for HCV. It slightly declined for HIV from 21% to 18% in one series and from 17% to 2% in another series. 10-34% of all individuals tested showed signs of at least one ongoing infection. Combined infections were frequently observed. The prevalence of viral markers was significantly dependent on the duration of drug use and if needle-sharing was practiced or not. Our data were analyzed in the context of the official notifications of these viral infections and related disorders to the Swiss Health Ministry. The risk of infections with the viruses analyzed here is 100-200 times higher in drug addicts than in the Swiss population. Drug users account for 42 to 52% of all infections (and clinical sequelae) notified in Switzerland. In the light of the fact that drug users also represent a potential source of spread of these viruses into the general population, the prevention effort in drug users should have first priority. PMID- 1411404 TI - [Patients returning after transplantation]. AB - Numerous reports have dealt with patient survival and prognostic factors after renal replacement therapy. However, few data exist for patients after a failed renal transplant and who start dialysis again. With this purpose, we retrospectively studied 36 patients who returned to dialysis after a mean transplantation time of 42.8 +/- 7.8 months. Actuarial patient survival on dialysis after the failed renal transplant (D2) was 78%, 74%, 69% and 41% at 1, 2, 3 and 5 years after restarting dialysis respectively. In comparison, survival of patients who started dialysis without a previous history of a renal transplant showed rates of 91%, 85%, 79% and 64% at 1, 2, 3 and 5 years respectively. The difference was statistically significant only at one year after beginning dialysis therapy (78% vs. 91%, p < 0.025). There were no differences in plasma urea concentration by the time of starting both first (D1) and second (D2) dialysis treatments (37.4 +/- 1.9 and 38.8 +/- 2.9 mmol/L respectively). Instead, a statistically significant difference was found between corresponding serum creatinine values (1100.1 +/- 47.1 and 856.9 +/- 50.0 mumol/L respectively, p < 0.05). When actuarial survival and serum creatinine values at the start of D2 were analyzed, there was a statistically better survival at 1 year for patients with serum creatinine values under 900 mumol/L, as compared with those above 900 mumol/L (85% vs. 52%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411403 TI - [Comparison of the efficacy of omeprazole/bismuth subcitrate or triple therapy in Helicobacter pylori gastritis. A prospective controlled study]. AB - In a controlled, prospective, randomized trial, 10 patients with Helicobacter pylori positive gastritis were treated either with triple therapy (tetracycline, ornidazole, bismuth subcitrate; T, Or, CBS), or omeprazole/CBS (O/CBS) to test the eradication rate of each treatment, its effect on gastritis and meal stimulated gastrin release. METHOD: 6 patients were treated with triple therapy and 4 patients with O/CBS for 2 weeks. Initially, and 0.5, 1, 3, 6, and 12 months after therapy, patients were investigated by a highly specific, quantitative Helicobacter serology, 13C-urea breath test and measurement of meal-stimulated gastrin release. After 3 and 12 months antral biopsies were taken endoscopically for rapid urease testing and culture. Activity of histological gastritis was graded. RESULTS: Eradication for at least 12 months was achieved in 5 out of 6 patients with triple therapy. Serology normalized and gastritis activity improved. In all patients treated with O/CBS, HP was suppressed only temporarily. No eradication was achieved. Urease testing and histology proved to be reliable tests for detecting HP. Culturing of HP was successful in only 66% due to technical problems. The 13C-urea breath test was correct in all cases. The initially, increased meal-stimulated gastrin release was normalized after eradication of HP. CONCLUSION: (1) Triple therapy is also successful in short term treatment in up to 80% of patients with HP gastritis and improves gastritis activity. (2) The combination O/CBS failed to eradicate HP in all treated patients. (3) The 13C-urea breath test and HP serology are reliable non-invasive parameters during follow-up. (4) Normalization of meal stimulated gastrin release after eradication of HP supports the hypothesis that HP induces increased gastrin release and hyperacidity. PMID- 1411405 TI - [Polymyositis: disease course and therapy with intravenously administered immunoglobulins]. AB - Corticosteroids and immunosuppressive agents are standard treatment for polymyositis (PM) and dermatomyositis (DM) respectively. Recent reports have emphasized a potentially successful regimen with intravenous immune gammaglobulins (IVIG). The short term success of this treatment in a personally observed case is described. IVIG treatment resulted in normalization of the serum concentrations of the muscle enzymes after continued inflammatory activity under treatment with azathioprine, cyclophosphamide and methotrexate in combination with corticosteroids. The improvement of PM by IVIG was further documented by an increase in muscle strength of up to 367% of the initial value and a regression of the myositic changes in the muscles of the thighs as evidenced by magnetic resonance imaging (MRI). The therapeutic response was paralleled by reversal of peripheral lymphopenia. Experience with IVIG treatment in PM/DM is reviewed and the potential role of this regimen in the management of PM/DM is discussed. PMID- 1411406 TI - [Risk assessment in professional drivers with coronary heart disease: experiences with the evaluation program for locomotive drivers by the Swiss Federal Railroad 1986-1991]. AB - BACKGROUND: For operational reasons in 1985 the question arose for the Swiss Federal Railways (SBB) whether engine-drivers (ED) with coronary heart disease (CHD) could be licensed for unaccompanied driving on certain well-defined premises. Until that year, such ED were allowed to drive only when accompanied by an apprentice ED. No generally accepted directives have operated in Switzerland for licensing ED or other professional drivers with CHD. METHODS: Based on data in the recent literature and assuming an acceptable mortality risk of about 0.75% per year, admission criteria were devised for licensing of ED with CHD for unaccompanied driving. Since 1986 every ED with CHD has been investigated according to these criteria by the medical service of the SBB in close cooperation with free practising and clinical cardiologists, and classified for driving alone, driving with accompaniment or as unfit to drive. ED who were fit to drive (either alone or accompanied) have checkups at least every three months by their family doctor and yearly by the medical service of the SBB and by a cardiologist for early recognition of any deterioration of their individual risk. RESULTS: From 1986-1991 a total of 114 ED were enrolled in the investigation program, 80 of whom proved to have CHD. 30 out of these 80 ED (37%) were cleared to drive alone at least for several months, 36 were licensed to drive with accompaniment for cardiac and non-cardiac reasons, and 14 were classified as unfit to drive. Among the ED driving without accompaniment, there was one death from heart failure during a total observation period of about 90 person-years, in an ED who had previously been re-classified for accompanied driving. One ED of the accompanied driving group died while on duty but not while driving. The annual incidence of new non-fatal CHD (non-fatal infarction, angina pectoris, ECG abnormality of proved coronary origin) was 0.25% in 1987 through 1991, for non fatal infarction alone 0.14%. CONCLUSIONS: Our relatively restrictive licensing procedure served to identify an acceptable number of ED with CHD who could resume unrestricted work without compromising public safety in the short run. Framing of similar criteria for public service vehicle drivers is advocated. PMID- 1411407 TI - [Arterial blood pressure measurement--which cuff?]. AB - In order to evaluate the influence of cuff size on blood pressure (BP) measurement, we compared values obtained with a standard cuff of 12 x 23 cm with those obtained with a large cuff of 15 x 28 cm in a group of 554 consecutive outpatients. Higher values were obtained with the standard cuff (systolic/diastolic 133.9 +/- 22/80.5 +/- 12 mm Hg) compared to the large cuff (128 +/- 21/76.5 +/- 11.6 mmHg (m +/- SD). This difference reached an average of 10/7 mm Hg for the large arm circumferences (AC) and for high blood pressure values. With the standard cuff, hypertensive values were found twice as often as with the large cuff. Thus the choice of a cuff adapted to AC is of great importance in identifying and treating hypertensive patients. In 77 subjects with a range of AC from 16 to 48 cm, the values measured with the standard and the large cuffs were then compared to those obtained with a reference triple cuff fitting to AC of 8.5 x 26-12 x 36-15 x 46 cm. The measurement of BP was most accurate when the ratio between cuff breadth and AC was between 0.42 and 0.44. The error increased by 0.6-0.7% per centimeter of AC above and below this ratio for the short inflatable bladders (twice as long as broad) of the standard and large cuffs. However, the use of long bladders (3 times as long as broad) combined with the triple cuff appreciably decreased this error.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411408 TI - [Monotherapy with the ACE-inhibitor ramipril or the calcium antagonist nitrendipine in essential hypertension]. AB - Angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have, by reason of their potentially favourable pharmacological profile, become increasingly established in the treatment of hypertension in recent years. In a double-blind randomized study with an initial placebo phase, carried out by practising physicians and thus aimed at the "usual" practice patients with essential hypertension, we assessed (1) the antihypertensive effect and tolerability of an ACE inhibitor (ramipril, 5 mg/d) or a calcium antagonist (nitrendipine, 20 mg/d) given in a single daily dose, and (2) a possible age dependent blood pressure (BP) effect of these therapies. In the 4 weeks' placebo phase, the two treatment groups were comparable as regards average age (49.6 and 49.4 years), age-range (27-67 and 25-64 years) and BP. Fifty-two patients completed the following 6 weeks' phase with active drug therapy. On ramipril (n = 26), the BP measured 24-25 hours after the last drug administration was reduced in the supine position from an average of 155/102 to 142/91 mmHg (mean reduction 10.1%) and in the upright position from 156/106 to 141/96 mmHg (-9.3%). Nitrendipine (n = 26) reduced the average BP from 155/102 to 147/94 mmHg (-6.8%) and from 155/106 to 146/99 mmHg (-6.6%) respectively. BP-lowering effects of both treatments were largely independent of age. Including the patients who discontinued the study prematurely because of side effects (1 on ramipril, 4 on nitrendipine), the "intention to treat analysis" shows BP normalization rates (diastolic < or = 90 mm Hg) of 55% (ramipril) and 30% (nitrendipine) respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411409 TI - [In-vitro fertilization--progress in a method of sterility treatment]. AB - The first IVF-baby (in-vitro fertilization) was born in England in 1978 and was greeted enthusiastically. But, despite the enormous effort invested, pregnancy rates were disappointingly low. Although in recent years the clinical pregnancy rate has increased worldwide to 15-20% per retrieval, a vast number of people remained unaware of this improvement. To demonstrate and analyze the progress of IVF we evaluated all 196 IVF treatments effected from 1988-1991 at Zurich University Hospital. With an initial clinical pregnancy rate of only 6% per retrieval in 1988, the rate improved to 35% (p < 0.025) in 1991. The crucial factors relating to this improvement were the 1990 introduction of the programmed short-term protocol for ovarian stimulation and reevaluation of the previously used embryo freezing technique. CONCLUSION: After a difficult start, IVF has become, if accurately indicated, a method of sterility treatment with a realistic pregnancy and delivery prospect. PMID- 1411410 TI - [Pericardial effusion in patients with malignant neoplasms]. AB - Pericardial effusions are often present in patients suffering from tumoral diseases, especially lung and breast cancers. Between September 1984 and February 1991 we observed 21 patients with "malignant pericarditis", of whom 57% had carcinoma of the bronchus and 33% a carcinoma of the breast. The symptoms most frequently seen were dyspnea (in 76% of the patients) and tachycardia (67%), accompanied by enlargement of the heart on chest radiograph. The effusions were bloody in all the patients, and the pericardial fluid cytology was positive in 9 of 10 of the lung cancer patients. 16 patients were treated by pericardiocentesis and in 10 of these thiotepa and hydrocortisone were instilled intrapericardially. In this manner it was possible to avoid recurrences of major effusion. The survival of the patients who received the intrapericardial instillation seems to be longer than that of the remaining patients. PMID- 1411411 TI - [Prevalence of anti-HCV (C100-3) antibodies in 20.373 blood donors]. AB - The anti-HCV antibody (C100-3) is present in the serum of 70-90% of patients that are carriers of posttransfusion non-A non-B hepatitis. This marker appears to be associated with a viral replication and infectiousness state. Since 1st August 1990 the Swiss Red Cross Transfusion Service has operated a systematic search for anti-HCV antibodies for every blood donation. The aim of the study was to establish the prevalence of anti-HCV antibodies in a donor population, look for the risk factors in the anti-HCV positive group, look for biological symptoms and signs of chronic hepatitis, and compare the data with that from an anti-HCV negative control group. From August to March 1991, 20,373 donors were tested by EIA (Ortho). The presence of anti-HCV antibody was confirmed by a neutralization test (Abbott). The donors in which both tests were positive formed the group studied (55 subjects). Their data was compared with that of a control group of anti-HCV negative donors. The prevalence of anti-HCV antibody in the group of 20,373 donors was 0.29%. Possible parenteral exposure to hepatitis C virus was found in 47% of anti-HCV positive subjects (30% blood transfusion, 9% i.v. drug addiction, 8% tattooing). 42% of the anti-HCV positive donors had no risk factor presently known for hepatitis C. 27% of anti-HCV positive donors had elevated transaminase levels. Until more effective screening tests are introduced it appears necessary to stress the previous history of future blood donors in order to search for hepatitis C risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411412 TI - [Pertussis in clinical practice--critical evaluation of diagnosis and epidemiology]. AB - In the Swiss Sentinel System pertussis is reported according to a clinical case definition. In our Sentinel practice, we have investigated in detail nine patients fulfilling these criteria. Seven of the nine patients have previously been vaccinated with whole cell vaccine. The clinical diagnosis could be confirmed in three cases by the detection of elevated serum IgA to filamentous hemagglutinin (FHA), and in one infant based on the peripheral blood lymphocytosis and the detection of pertussis in other family members. The likely diagnosis in another brother and sister pair was a parainfluenza virus infection, possibly with concomitant pertussis. Two sisters probably had a mycoplasmal infection, which in one was accompanied by pertussis. In two patients an infectious etiology could not be determined. The laboratory tests which have been used in these cases are discussed. The occurrence of pertussis in previously vaccinated adolescents and adults has been recognized worldwide and is of epidemiological concern in view of current vaccination policies. The Swiss Sentinel System could play an important role in the surveillance of pertussis in Switzerland. PMID- 1411413 TI - [Cardiovascular effects of everyday coffee consumption]. AB - Whereas the earlier literature contains several studies on the acute cardiovascular effects of caffeine, systematic studies of the cardiovascular effects of regular daily coffee consumption have appeared only recently. Acute caffeine administration (total daily amount in one dose following caffeine abstinence) increases both systolic and diastolic blood pressures by 10-15 mm Hg and lowers the pulse by about 2-5 beats/min. Repeated caffeine administration leads to a rapid decline in the blood pressure response. Chronic switching between decaffeinated and caffeine-containing coffee showed no more than marginal changes in blood pressure. Plasma lipids are probably independent of caffeine consumption, but increase slightly with boiled (compared with filter) coffee. The question of the thermogenic effect of coffee consumption remains open. The prevalence of coronary disease appears to be epidemiologically independent of coffee consumption. PMID- 1411414 TI - [Concerning: "Anaphylactoid reaction to Physiogel SRK 4%--a contribution to the controversy on plasma substitute agents" by T.A. Cron and H. Gerber (Schweiz. med. Wschr. 1991; 127: 1773-1776)]. PMID- 1411415 TI - [Molecular genetics diagnosis of Steinert's myotonic dystrophy]. AB - Myotonic dystrophy (DM) is the most common neuromuscular disease with adult onset (incidence 1 in 8000). The biochemical basis of this autosomal dominantly inherited disease is still unknown. The most striking features are myotonia and progressive muscular wasting. There is high variability of disease severity in patients from different families, but also within the same family. For practical reasons three subtypes can be defined: The classical adult onset form of the disease, a mild form with late onset and/or very moderate symptoms, eg. cataracts only, and the most severe congenital form which is transmitted by affected females. Furthermore, the progression of DM in affected families may exhibit an increase in the severity of the disease in successive generations. This observation is called anticipation. Very recently the DM gene has been cloned and an unstable DNA sequence specific for the disease has been characterized. Detection of an enlarged DNA fragment due to the expansion of a trinucleotide (CTG) repeat within the DM gene can be used for direct DNA diagnosis in affected individuals and persons at risk. Furthermore, there is a strong correlation between the length of fragment expansion and the degree of disease severity in gene carriers. We report here our preliminary results of the investigation of over 70 patients and demonstrate the clinical usefulness of this new method by the findings in three families. PMID- 1411416 TI - [Non-enzymatic marking of gene probes using digoxigenin for the diagnosis of sickle cell mutation and beta thalassemia]. AB - A method is described in which allele-specific oligonucleotides (ASO) are labeled non-enzymatically with digoxigenin (DIG). The ASOs were synthesized in a DNA synthesizer. A primary C6-alkylamine was incorporated at the 5'end of the ASO. The derivative was coupled to digoxigenin-3-0-methylcarbonyl-epsilon-aminocaproic acid-N-hydroxy-succinimide ester. The DIG-ASO probes were isolated from the crude preparation and hybridized with amplified genomic DNA. The annealed probes were detected with an ELISA test. The DIG-ASO probes were successfully used for the identification of sickle cell disease genotypes and the most common beta thalassemia mutations. PMID- 1411417 TI - [The effect of first aid and care times on the clinical course and treatment results in multiple trauma. Initial interim results of an interdisciplinary trauma registry in the St. Gallen district hospital]. AB - QUESTION: To date little is known about the influence of variable rescue (i.e. transportation/preclinical care) and clinical care times on the clinical progress and outcome of patients suffering injuries ranging from average to severe. Having examined this question within the framework of an ongoing study of trauma, we present the first provisional results and compare them with existing documentation. METHOD: Since 15 June 1990, all cases of multiple injury have been recorded in a trauma register. The present interim investigation of 143 patients covers a period of 13.5 months. We have recorded the rescue and clinical care times and compared them with survival, disability, complications and length of stay in hospital or intensive care unit. RESULTS: 106 (74%) of the total of 143 patients were operated on an average of 5.5 hours after the accident. In cases of intracranial or intraabdominal bleeding, there was an average time lag of 220 minutes after the accident before the patient could undergo surgery. Overall, 70% of the total rescue time was spent on medical attention and waiting time in the emergency unit. The secondary transfer rate is 46%. In the case of 4 patients, it is possible that the delays involved contributed appreciably to mortality (19%. i.e. 4/21). Generally, however, no coherent and conclusive correlation could be established between prolonged rescue and clinical care times and a worsened outcome. False negative results cannot be totally excluded, since the classification of the individual degree of injury by means of ISS and TRISS is unreliable, the variable quality of medical care prior to arrival at our emergency unit has not been taken into account, and the case figures are low (possibly of a large-scale beta error). CONCLUSIONS: The database for the assessment of standard times is still inadequate. For a reliable analysis, a total number of at least 500 patients is necessary (beta error acceptable). Our own data and the meagre results of other studies support the supposition that it is not the absolute time-lapse which has prognostic significance but the qualified medical assistance provided within a critical, individual, but extremely variable time-span. The increased employment of highly qualified emergency staff and a more efficient "triage", in the sense of a clearly directed trauma regionalization, could thus lead to optimization of trauma care. PMID- 1411418 TI - [Severe thrombocytopenia in systemic Boeck's disease]. AB - We present a case of sarcoidosis-associated severe thrombocytopenia, a rare but well known complication. Diagnosis of sarcoidosis was based on radiologically enlarged hilar and mediastinal lymph nodes and on histology of biopsies taken from them by mediastinoscopy. In most cases an autoimmune etiology is assumed and platelet-associated antibodies can be demonstrated. Therapy resembles that of chronic idiopathic thrombocytopenia; an early start, sufficient duration and slow reduction of the corticosteroid medication is crucial. If bleeding complications occur, high-dose human gamma-globulins are indicated. In the light of the literature the pathophysiological, diagnostic and therapeutic aspects of this potentially lethal complication are discussed. PMID- 1411420 TI - [Ehrlichiosis in dogs: literature review and case description]. AB - A case of E. canis in a 7 year old intact female bearded collie is described and possible clinical signs of Ehrlichiosis are discussed. Non-specific findings included elevated rectal temperature, depression and anorexia. Additional findings were generalized lymphadenomegaly, myalgia and painful swollen joints. Significant changes in the CBC were leucopenia and thrombocytopenia. The positive E. canis titer of 1:40 and rising titer to 1:160 were specific for Ehrlichiosis. Doxycycline and prednisolone were needed to obtain clinical remission, which underlines, that immune-mediated processes are important in the pathogenesis of Ehrlichiosis. PMID- 1411419 TI - [Fish diseases in Switzerland. A statistical evaluation of the diagnostic material of the Fish Research Institute from 1979-1988. II. Special aspects]. AB - The frequency of fish diseases diagnosed at the Fish Disease Laboratory at the University of Berne from 1979 to 1988 is presented. Parasitic infections have been found to be the most frequent diagnosis. Among noninfectious diseases poisonings were predominant. Six infectious diseases have been considered to be economically relevant. These diseases (according to their frequency: Gyrodactylosis, Costiosis, Ichthyophthiriosis, Viral Hemorrhagic Septicemia (VHS), Saprolegniosis and Furunculosis) were further analysed. Their incidence varies with season, species, origin and length of fish. Possible explanations for these findings are discussed. PMID- 1411421 TI - [Bacteriology and mycology of otitis externa in dogs]. AB - The bacterial and fungal flora of 1118 ears of dogs with otitis externa and 100 ears of healthy control dogs were studied in order to isolate the causative agents. The yeast Malassezia pachydermatis (56%) was by far the most common organism in otitic dogs followed by the bacteria Staphylococcus intermedius (23%), Pseudomonas aeruginosa (12%), Proteus spp. (6%) and Streptococcus canis (5%). A statistical analysis of observed results showed that the incidence of these organisms is significant in otitic dogs. Many strains of S.intermedius, P.aeruginosa and Proteus spp. are resistant to antimicrobial agents commonly used to treat otitis externa. Therefore an antimicrobial susceptibility testing was performed using "Cobas Bact" for these bacterias. Furthermore, 80 strains of M.pachydermatis were submitted to identification-kits (API 20 CAUX, API STAPH, Cobas Micro). The observed results showed that an identification with these tests was not possible. PMID- 1411422 TI - [Mechanism of multidrug resistance in human cancers]. PMID- 1411423 TI - [Advances in research on photosensitizers]. PMID- 1411424 TI - [Advances in research of endothelin]. PMID- 1411425 TI - [Histochemical studies on the medial regions of the brainstem in guinea pigs]. PMID- 1411426 TI - [Relation between oncogenes, aging and pathogenesis of tumor]. PMID- 1411427 TI - [Intracellular control of contractility for airway smooth muscles]. PMID- 1411428 TI - [Pancreastatin]. PMID- 1411429 TI - [Biosynthesis and biological activities of lipoxins]. PMID- 1411430 TI - [Immunity of erythrocytes]. PMID- 1411431 TI - [Computer simulation in studies on mechanisms of action of antiarrhythmic agents]. PMID- 1411432 TI - [Advances in research of diffuse noxious inhibitory controls]. PMID- 1411433 TI - [Complex carbohydrates in intercellular matrix and cytoplasm]. PMID- 1411434 TI - [Endothelin and hypertension]. PMID- 1411435 TI - [Physiological functions of unmyelinated nerve fibres]. PMID- 1411436 TI - [Adult respiratory distress syndrome and pulmonary surfactant replacement therapy]. PMID- 1411437 TI - [Anti-morphine-analgesic sites of cholecystokinin octapeptide in the central nervous system and the mechanism of its involvement in the formation of morphine tolerance]. PMID- 1411438 TI - [Parathyroid hypertensive factor]. PMID- 1411439 TI - [Regulation of lymphokine-activated killer (LAK) cells by cytokines]. PMID- 1411440 TI - [Functional reorganization of the somatosensory cortex]. PMID- 1411441 TI - [Implantation of genetically modified endothelial cells. A new promising technique for gene therapy]. PMID- 1411442 TI - [Endothelin in the central nervous system]. PMID- 1411443 TI - [Humoral mechanism of renal effects during left atrial distension]. PMID- 1411444 TI - [Physiologic and pathologic significances of myocardial contractile ATPase]. PMID- 1411445 TI - [Influence of protein and amino acid on blood lipid]. PMID- 1411446 TI - [Arachidonic acid metabolites in the liver and gallbladder]. PMID- 1411447 TI - [Progress in the study of human requirement and safe range of dietary selenium intake]. PMID- 1411448 TI - [Arthroscopy of the shoulder]. AB - Shoulder arthroscopy has grown considerably for several years in a row. The progress obtained nevertheless should not lead to an underrating of both clinical and para-clinical investigations. Arthroscopic technique as applied to the shoulder joint has now reached a mature state. Diagnostic benefits due to arthroscopy are scant because the recent development of medical imaging techniques made its usefulness less obvious. A great number of reliable therapeutic acts are currently performed as well in the glenohumeral joint, as in the sub-acromial space. PMID- 1411449 TI - [Physical performance and sedation: comparative study of the effects of a benzodiazepine (temazepam) and of a non-benzodiazepine hypnotic (zolpidem)]. AB - It is well-known that many athletes experience some form of precompetition stress that may result in insomnia during the night before their competition. Yet, sleep withdrawal even if only partial, has a negative influence on performance, particularly when the type of exercise requires good psychomotor performance The purpose of the present study was to investigate whether the intake of a hypnotic drug would have negative effects on physical performance capacity. The authors have compared the effects of oral temazepam, a medium half-life benzodiazepine vs oral zolpidem, a short half-life non-benzodiazepine drug, vs placebo. A randomized double-blind trial was used to assess endurance, resistance, strength and coordination in 26 athletes. The results did not show any differences between the three groups, neither in physical performance characteristic nor in coordination. It is concluded that as regards the performance capacity, there is no risk for stressed athletes to use sleep inducers the night before their competition. PMID- 1411450 TI - [Medicolegal aspects of mountain rescue for the emergency physician and personnel]. AB - The remarkable spread and growth of mountain sports, as well as of their unfortunate succession of injuries sometimes give rise to medico-legal problems which up to now have been dealt with only in a very little number of publications. We discuss here briefly the main problems of setting up and organising the first aid and rescue squads and the resulting legal responsibility the health and medical staff may be exposed to. PMID- 1411452 TI - Diagnosis by DNA. PMID- 1411451 TI - On the epidemiology of sports injuries in Switzerland. AB - A review of the current literature and of insurance data sources on sports injuries in Switzerland during the latest decade is presented. Epidemiological denominator data to determine the population-at-risk and the exposure time are scarce and it is therefore recommended that both the quantity and the quality of Swiss research in this field will be enhanced. It is also proposed that at least one academic institution in Switzerland would assemble systematically all available data of standard format on sports and recreational injuries to ensure a continuous analysis of these data. PMID- 1411453 TI - Formula for diabetes? Cow's milk for infants may contribute to the disease. PMID- 1411454 TI - Mountain sickness. AB - The varied and subtle symptoms of this potentially lethal disorder humble many who scale the summits. But the problem is often preventable. PMID- 1411455 TI - Histones as regulators of genes. AB - Histones were once dismissed as little more than packing material for nuclear DNA. In fact, these proteins can both repress and facilitate activation of many genes. PMID- 1411456 TI - On treating AIDS. PMID- 1411457 TI - Scavenging and human evolution. PMID- 1411458 TI - Jumbling the genes. PMID- 1411459 TI - Intercepted messages. New biotechnology drugs target intracellular communication. PMID- 1411460 TI - Intuitive design. Artificial intelligence helps a drugmaker learn what works. PMID- 1411461 TI - Paradise lost? Microbes mount a comeback as drug resistance spreads. PMID- 1411462 TI - Health care reform. PMID- 1411463 TI - Visualizing biological molecules. PMID- 1411464 TI - The big bang of animal evolution. PMID- 1411465 TI - [New aspects in the evaluation of Doppler blood flow curves: three- dimensional image and analysis of Doppler shift frequencies within the heart cycle]. AB - Since the introduction of Doppler ultrasound to the area of medical diagnostics, there have been numerous improvements and important technical refinements. In obstetrics, Doppler examination allows a more accurate and encompassing evaluation of the foetal condition than was previously possible. Combined with today's sophisticated computer technology, it has a great potential in research and to expand our knowledge about the physiology and pathophysiology of foetal and maternal haemodynamics. This paper describes a new way of integrating another factor into the evaluation of Doppler blood flow waveforms, namely, the intensities of various frequencies. One result should be more detailed information about the given haemodynamic situation; another, a valuable tool for the quality control of Doppler blood flow measurements. Although our work was on applications in the field of obstetrics, the method we have developed can be used in all medical areas. PMID- 1411466 TI - [Comparison of different blood flow parameters for evaluating blood flow spectra in fetal growth retardation]. AB - Uteroplacental and foetoplacental vascular resistance is generally high in pregnancies complicated by intrauterine growth retardation. Assessment of flow velocity curves using angle-independent indices as A/B ratio, resistance index (RI) or pulsatility index (PI) cannot classify all cases with pathological flow velocity profiles. Beneath the pulsatility the maximum frequency outline of the flow velocity waveform offers additional clinical information. The evaluation of flow velocity curves using polynome analysis (including III degrees) provides additional data including occurrence of diastolic notching and can be used as a more sensitive indicator of impaired uteroplacental blood flow. In such pregnancies accurate evaluation of the maximum flow velocity outline with polynome analysis has been shown to be an important qualitative criterion in the assessment of blood flow velocity waveforms. PMID- 1411467 TI - [Doppler sonography of the umbilical artery for evaluating the fetoplacental vascular tree: a prospective histologic comparison]. AB - We compared the clinical data, Doppler sonographic results and histological placental findings of 252 patients prospectively. A normal flow velocity wave form may be related either to a normal placenta villous and vessel architecture or to an at least focal leason with compensatory angiosis and/or high placental weight, whereas in cases with missing compensation phenomenon the end-diastolic blood flow velocities in the umbilical arteries are reduced. PMID- 1411468 TI - [Umbilical blood flow relations in different segments of the umbilical cord. Part 1. Physiologic index constellation]. AB - Based on a collective of 500 women with normal singleton pregnancies we examined the indices of flow resistance along the umbilical cord. Measurements were taken at the foetal abdominal side of the Aa. umbilicales on the one hand and at the placental insertion of the vessels on the other. According to our results we were able to establish a physiological constellation of the indices for each week of gestation, and - subsequently - for the whole duration of pregnancy. These constellations could be considered physiological. They may serve as a basis for the definition of pathological conditions. PMID- 1411469 TI - [The normal vascularization of the female breast in Doppler ultrasound]. AB - Specific Doppler-Ultrasound methods for the differentiation of benign and malignant lesions by measurement of abnormal flow, have been known for more than 10 years. We used this method also in many patients without pathological breast problems and found a high physiological variation of blood flow. As basic definition of normal flow, to be compared with patients under medical treatment of mastopathy, we studied flow variations during menstrual cycles in normal volunteers. In both breasts we measured the amount of vessels, average frequency shifts according to flow velocity and the sum of all Doppler shifts, as measurement of the overall vascularity. Between different individuals the range of Doppler shifts was between 500 and 1000 Hz. However, in individual subjects the variation was only between 50-200 Hz, average 100 Hz. We also found between contralateral breasts no remarkable difference in vascularity. Flow increased at the 10th day after onset of menstruation, in 9 cycles with ovulation and in 8 cycles with a lack of gestagen production. Dramatic flow increase occurred in one early pregnancy. It appears that influences of drugs can be controlled, after basic measurements of individual vascularity. PMID- 1411470 TI - [Ultrasound image of endometrial cancer]. AB - In this prospective study 571 patients with postmenopausal bleeding/discharge (group I) and 300 patients without symptoms (group II) were ultrasonographically examined. The sonographic findings were compared with those of histology to evaluate the value of ultrasonography in endometrium diagnosis. The main parameters which we considered in the diagnosis of malignancy of the endometrium, were the thickness of the endometrium, the boundary of the endometrium, homogeneity and collection of fluid in the uterine cavity. However, the size of the uterus and the central endometrial echo were found not to be sensitive signs of malignancy. The sensitivity of sonography in group I was 86.3% higher than group II which is 75%. The rate of false-positive and false-negative in the total study population was 7.1%. We believe that ultrasonography is the easiest, most painless out-patient based and non-invasive diagnostic method in comparison to all other endometrium diagnostic measures, and is an advance towards better approach in the early diagnosis of endometrial carcinoma. PMID- 1411471 TI - [Attempt at three-dimensional imaging in obstetrics]. AB - Different attempts have been already made to present sonographic findings in 3 dimensions. In most of computer assisted systems the time for acquiring and data processing is too long to allow for an instantaneous interaction between the examiner and the machine; furthermore, valuable data; concerning the organ structure were lost. The aim of the system presented here is to acquire short time a sample volume for 3 dimensional display without employing an expensive periphery, containing all relevant sonic data and without substantial changes in handling the equipment. The technical details, advantages and shortcomings of the equipment are discussed. First results in obstetrics and gynaecology are presented. PMID- 1411472 TI - [Ultrasound diagnosis of lumbar intervertebral disk displacement--a clinically relevant method?]. AB - In a prospective clinical study, 102 patients suffering from low back pain were examined by ultrasound. In all patients the segments L3/4, L4/5, and L5/S1 were evaluated. We analysed a total of 306 lumbar disc segments. Ultrasound evaluation was transabdominally performed by using a 3,5 MHz scanner. The results of the ultrasound documentation were compared to MRI or if the patient was operated on with the intraoperative findings. In 25 disc the dorsal border of the disc could not be demonstrated by ultrasound. The statistical analysis resulted in the following values: [table: see text] Comparing these results with the results of other imaging modalities like myelography, CT, or MRI, ultrasound scores are significantly inferior. CLINICAL RELEVANCE: With the present technique ultrasound does not seem to be of diagnostic value for patients with herniated disk. PMID- 1411473 TI - [Color-coded duplex sonography and ultrasound contrast medium in the study of peripheral arteries--initial clinical experiences]. AB - Ultrasound contrast agents (US-CA) amplify reflected sound waves. Most substances used as contrast agents are destroyed when passing the lungs. SH U 508 is a new US-CA that can pass the lungs without impairment after peripheral intravenous application. In a clinical trial of this US-CA, we investigated its effect on the visualization of blood movement in peripheral arteries by color-coded Duplex sonography (CCDS). The leg arteries of 20 patients with severe chronic arterial occlusion were examined by CCDS (QAD I and Platinum) after i.v. application of the US-CA. After passage of the pulmonary capillaries, the US-CA amplified blood flow signals in the arterial system in a dose-dependent manner with both systems used. Undesired side-effects were not observed. The amplification produced by appropriate concentrations of the US-CA markedly improved the visualization of blood movement. Further studies are required to determine the optimal dosage and application technique as well as the indication for using this US-CA. PMID- 1411474 TI - [Diagnosis of cephalothoracopagus--a case report]. AB - Cephalothoracopagus twins were diagnosed at 22 weeks' gestation, hence this case was diagnosed early enough antenatally to allow vaginal pregnancy termination. This case underlines the need for exact ultrasound screening during early pregnancy. PMID- 1411475 TI - Is there a role for natural remedies in rheumatoid arthritis? PMID- 1411476 TI - Outcome after thymectomy for myasthenia gravis: a retrospective review. AB - This is a retrospective study of 54 patients, who in the period November 1977 to November 1986 underwent thymectomy as treatment for myasthenia gravis. Patients in whom difficulty attempting complete excision of the gland was anticipated were selected for a transthoracic procedure. All others underwent an initial transcervical approach, proceeding to an upper sternal splitting incision if further access was required to remove adequately a large gland. The sample was split almost equally between the two surgical procedures. Patients in the transthoracic group were significantly older and experienced significantly greater peri-operative morbidity or mortality. There was no significant difference in outcome between the two groups, 52% achieving a good result (defined as remission or clinically significant improvement of symptoms) that was sustained over the five year follow-up period. In our opinion, complete removal of the thymus should be the goal of surgical treatment for myasthenia gravis. PMID- 1411478 TI - Thrombolytic therapy: impact on coronary care in a district general hospital. AB - The introduction of routine thrombolytic therapy in the Cardiac Care Unit (CCU) of a District General Hospital has resulted in an increased demand for admission particularly in the 70+ age group. Complications and side effects of such treatment have been similar to those reported in several large multicentre trials. The percentage of patients with myocardial infarction receiving thrombolysis has increased to 60% with the commonest reason for withholding of such treatment being the lack of ECG changes. Mortality rates have fallen and there has been an increased referral rate for urgent angiography. To maximise benefit CCU's should encourage early direct admission and ensure that, if not present on site, facilities for angiography can easily be arranged. PMID- 1411477 TI - Malaria in Aberdeen: an audit of 110 patients admitted between 1980-1991. AB - All 110 patients seen in North East Scotland after contracting malaria from foreign travel were treated in the Regional Infection Unit in Aberdeen. Those patients managed there from January 1980 to March 1991 are described. There were 54 episodes of Plasmodium falciparum malaria (49%) and 26 episodes (23%) of Plasmodium vivax malaria. The remainder had either mixed infection or were diagnosed as malaria on high clinical probability. The majority of the patients were male (80%) and under 40 years of age (84%). Most patients were either caucasians born in the UK (69%) or native Africans (23%) who were students recently arrived for further education or who had returned from visiting their country of origin for summer holidays. The British residents acquired infection either while on oil related business in West or Central Africa (46%) or after travelling on holiday (30%). The peak incidence of presentation was August and September. 93.5% of patients with falciparum malaria had returned or originated from Africa. 42% with vivax malaria had visited Africa and 27% Papua New Guinea. 70% had been prescribed antimalarial prophylaxis but less than half of these took their medication correctly. The majority of patients with falciparum malaria presented within two weeks of arrival in Britain while patients with vivax malaria presented at varying (but generally longer) intervals, 42% being diagnosed more than three months after exposure. Falciparum infection was more severe although there have been no deaths in the unit from malaria. Our experience seemed of interest and worth reporting because of the number of patients whose infection reflected travel related to the off shore oil industry, which is centred in Aberdeen. PMID- 1411479 TI - Time trends and geographical variation in Parkinson's disease in Scotland. AB - Parkinson's disease is a common and disabling condition which principally affects the elderly. The time and space distribution of Parkinson's disease has been examined to determine if it provides clues as to aetiology and factors affecting its distribution. Previous studies have used mortality data, data from epidemiological studies, and prescribing information particularly with regard to the use of levodopa. These studies have looked within countries and between countries. PMID- 1411480 TI - Streptococcus milleri and complex groin abscesses in intravenous drug abusers. AB - Intravenous drug abuse is an increasing problem. Septic complications occur frequently at the injection site, especially in the groin where large abscesses around the femoral vessels can threaten life or limb. We report four patients with extensive or complex groin abscesses following attempted self-injection into the femoral vein. Streptococcus milleri was cultured from all of these abscesses and prompted a review of the isolation of this organism in this hospital. PMID- 1411481 TI - Astrocytoma presenting with vasculitis. AB - A cerebral astrocytoma which had remained quiescent possibly for 12 years, presented with blackout, vasculitis and a lupus-like (L-E like) syndrome. The association between tumours and "L-E like" syndromes is reviewed briefly. PMID- 1411482 TI - "A beloved physician" John Abercrombie MD (EDIN) FRCSE, FRCPE, MD (Oxon) 1780 1844. AB - This son of an Aberdeen minister, graduating MD in Edinburgh in 1803, established a leading practice in that city, attracting apprentices to study medicine and patients of all classes of society from throughout Scotland. Sir Walter Scott in his later years was one who relied on his medical expertise. Dr Abercrombie, a Fellow of both the Royal College of Surgeons and Royal College of Physicians, Edinburgh, was in the forefront of Edinburgh medicine. An extensive author, primarily on medical subjects and laterally turning to metaphysical, moral and religious works, he gained a reputation among intellectuals world-wide. A philanthropist, he gave large amounts of financial aid to Missionary Societies, both at home and overseas. A founder member of first President of the Edinburgh Association for Sending Medical Aid to Foreign Countries (two years later renamed the Edinburgh Medical Missionary Society). PMID- 1411483 TI - Surgeons and HIV. PMID- 1411484 TI - Odontoid fracture in the elderly: a case report of the screw fixation technique. AB - The case of a type II, highly unstable, odontoid fracture in a 92 year old patient is reported. This fracture was treated by a new technique for anterior odontoid screw fixation with excellent results. The authors discuss this technique and treatment options for odontoid fracture in the elderly. PMID- 1411485 TI - Once is not enough. Rational use of the blood culture. PMID- 1411486 TI - Research in context (or if you want to study how fox and chickens relate, go to the hen house, not the zoo). AB - The context in which the research is carried out frequently is as important as the research question being investigated. The fact certainly is the etiology for many of the problems practicing physicians face when applying traditional research findings to clinical practice. The recent development of a family practice research network in South Dakota brought the investigators face to face with divergent views on this issue. This article provides some insight into different research philosophies. PMID- 1411487 TI - New macrolide antibiotics. PMID- 1411488 TI - It's back. PMID- 1411489 TI - Pine Ridge IHS Primary Care Resident Rotation. AB - With the support of the Oglala Sioux Tribe and the Aberdeen Area Indian Health Service, the University of South Dakota School of Medicine initiated development of a primary care resident rotation at the Pine Ridge IHS provider site. The rotation was conceived in an effort to help address the problem of recruitment and retention of physicians at Pine Ridge in the long term, while offering a unique educational experience for residents. It is a cooperative effort of four neighboring medical schools in South Dakota, North Dakota and Nebraska. Similar relationships between tribes, the Indian Health Service, and medical schools are encouraged, with the belief that such endeavors will assist in stabilizing professional staffs at provider sites, and lead to improved health care of the Indian people. PMID- 1411490 TI - When the stigma is gone (is this alcoholism?). A parable. PMID- 1411491 TI - Generation of mutagenicity by ozonation of humic substances' components. AB - Components of humic substances, such as vanillin, syringaldehyde, vanillic acid and di-n-butylphtalate, were ozonated and subjected to the mutagenicity assay using Salmonella typhimurium TA 98 and 100 with and without S9 mix. The strong mutagenic activity was found on all components except di-n-butylphtalate by strain TA 100 with and without S9 mix. Substances with strong mutagenic activity in ozonated vanillin were water-soluble and were slightly extracted with benzene, dichloromethane and ethyl acetate. Following gel chromatography on Sephadex G-10, the strong mutagens generated by ozonation were found with molecular weights greater than 300. PMID- 1411492 TI - Urban air pollution by polycyclic aromatic hydrocarbons: levels and sources of variability. AB - The atmospheric levels of polycyclic aromatic hydrocarbons (PAHs), measured since the mid-1970s from approximately 60 towns world-wide, are reviewed. For each investigation, a concise description of sampling conditions and analytical methods is also given. The strongly carcinogenic benzo[a]pyrene was typically found in the range of 1-20 ng/m3 in Europe, and around 1 ng/m3 in the USA. For other PAHs, individual concentrations were generally in the range of 1-50 ng/m3 in Europe, 0.1-1 in North and South America and in Australia, 1-10 in Japan, and 10-100 in two towns in India and New Zealand. Data on the size distribution of PAH-containing particles are also presented, showing that PAH content is adsorbed mostly on respirable particles. The ratios of winter to summer levels, and of urban to rural levels, were found in the range of 2-10 in both cases. PAH levels have progressively decreased in the last few decades, most probably due to the introduction of anti-smoke regulations and the decrease of coal burning for heating. Measurements from different investigations can only be compared with great prudence, owing to sampling factors which can affect results. Sources of urban PAH contamination and of the variability in levels are discussed. PMID- 1411493 TI - Monitoring of air for microbial and metal contamination at selected sites in the vicinity of Johannesburg, South Africa. AB - A preliminary survey was undertaken to identify air contamination in the vicinity of industrial, residential and hospital sites. In many developing countries, poor town planning has resulted in growth of residential and commercial sites in close proximity to the industrial works, without the provision of a buffer zone. As prevailing winds blow across the industrial works to the other areas, undesirable pollution may be experienced. Before steps are taken to reduce factory emissions, the impact of the industry on the surrounding area needs to be clearly defined. In this study, the total particulate matter and the level of microbial contamination at the selected sites is reported. The elemental composition of the particulate matter is described. PMID- 1411494 TI - Carboxyhemoglobin levels in blood donors in Bahrain. AB - A total of 107 venous blood samples were obtained from blood donors in Bahrain for carboxyhemoglobin (COHb) analysis. The donors were categorized according to their sex, smoking habits, occupation, place of work (indoor or outdoor), and residential area. The mean COHb levels were significantly higher in smokers (4.8%) than nonsmoking (1.5%). The mean COHb levels were higher in smoking, outdoor working donors (4.98%) and nonsmoking outdoor working donors (2.29%) than smoking indoor working donors (3.07%) and nonsmoking indoor working donors (1.04%). Other factors, such as sex and residential area did not influence COHb concentrations. The results indicate a possible influence of the levels of environmental carbon monoxide on the COHb in the blood of the Bahraini population. PMID- 1411495 TI - Migration of radiocesium in two forest soils as obtained from field and column investigations. AB - Depth profiles of radiocesium were measured in a podsolic parabrown earth of a spruce stand and in a podsol of a pine stand up to 3 years after the Chernobyl accident. At the same sites undisturbed soil columns of 20 cm diameter and 40 cm length were taken, transferred to the laboratory and irrigated intermittently with synthetic rainwater containing initially a known amount of radiocesium. The resulting migration of radiocesium in the columns under unsaturated conditions was determined as a function of time up to 3 years with a scanner technique. The depth profiles of radiocesium observed in the field and in the columns were evaluated with a compartment model to obtain the residence half-times of this radionuclide in the various soil horizons. The field observations yielded a residence half-time in the organic layer of both soils of approximately 4-6 years for Chernobyl-derived cesium, and of 10-15 years for cesium from the global fallout of weapons testing. In the mineral soil (0-5 cm), under spruce the residence time of Chernobyl-derived cesium was 15 years, that of cesium from the global fallout (present in the soil since approximately 30 years) was 50 years. Under pine, the residence time in the mineral soil was 4 years for Chernobyl derived cesium and 11 years for global fallout cesium. Obviously, in each layer of both soils cesium becomes less available for migration with time. The residence times of radiocesium evaluated from the column experiments were in good agreement with those obtained from the field observations. Due to the comparatively short duration of the column experiments, however, the long-term increase of the residence time of radiocesium in the soil was not yet unambiguously observable. PMID- 1411497 TI - HIV-free AIDS reports. PMID- 1411496 TI - Lyme disease: asking the right questions. PMID- 1411498 TI - Gene therapy. Monkey tests spark safety review. PMID- 1411500 TI - Gene patents. Rumors fly over rejection of NIH claim. PMID- 1411499 TI - AIDS patent dispute. U.S. officials say non on royalties. PMID- 1411501 TI - New French biomedical center breaks the mold. PMID- 1411502 TI - 30-million-year-old DNA boosts an emerging field. PMID- 1411503 TI - Hungarian fossils stir debate on ape and human origins. PMID- 1411504 TI - Weighing naked proteins: practical, high-accuracy mass measurement of peptides and proteins. AB - Two new technologies have made the study of proteins by mass spectrometry straight-forward. Proteins with molecular masses of up to more than 100 kilodaltons can be analyzed at picomole sensitivities to give simple mass spectra corresponding to the intact molecule. This development has allowed unprecedented accuracy in the determination of the molecular weights of proteins. A number of "case studies" are used to present the revolutionary impact that these powerful new ways of looking at proteins are having on biological research. PMID- 1411505 TI - From molecules to cells: imaging soft samples with the atomic force microscope. AB - Since its invention a few years ago, the atomic force microscope has become one of the most widely used near-field microscopes. Surfaces of hard sample are imaged routinely with atomic resolution. Soft samples, however, remain challenging. An overview is presented on the application of atomic force microscopy to organic samples ranging from thin ordered films at molecular resolution to living cells. Fundamental mechanisms of the image formation are discussed, and novel imaging modes are introduced that exploit different aspects of the tip-sample interaction for local measurements of the micromechanical properties of the sample. As examples, images of Langmuir-Blodgett films, which map the local viscoelasticity as well as the friction coefficient, are presented. PMID- 1411507 TI - Miocene fossil hominids and the chimp-human clade. AB - Miocene hominoids from Europe are among the earliest members of the great ape and human clade (the Hominidae). One of these forms, represented by well-preserved cranial remains from Rudabanya, Hungary, sheds new light on the question of the evolutionary relations among living hominids. This new evidence supports the view that humans have a specific evolutionary relation with chimpanzees, to the exclusion of all other apes. PMID- 1411506 TI - Interactions of small nuclear RNA's with precursor messenger RNA during in vitro splicing. AB - Precursor messenger RNA splicing requires multiple factors including U1, U2, U4, U5, and U6 small nuclear RNA's. The crosslinking reagent psoralen was used to analyze the interactions of these RNA's with an adenovirus precursor messenger RNA in HeLa nuclear extract. An endogenous U2-U4-U6 crosslinkable complex dissociated upon incubation with precursor messenger RNA. During splicing, U1, U2, U5, and U6 became crosslinked to precursor messenger RNA and U2, U5, and U6 became crosslinked to excised lariat intron. U2 also formed a doubly crosslinked complex with U6 and precursor messenger RNA. The U1, U5, and U6 crosslinks to the precursor messenger RNA mapped to intron sequences near the 5' splice site, whereas the U2 crosslink mapped to the branch site. The kinetics of crosslink formation and disappearance delineates a temporal pathway for the action of small RNA's in the spliceosome. Potential base pairing interactions between conserved sequences in the small nuclear RNA's and precursor messenger RNA at the sites of crosslinking suggest that the 5' splice site is defined in several steps prior to the first cleavage event. PMID- 1411508 TI - DNA sequences from a fossil termite in Oligo-Miocene amber and their phylogenetic implications. AB - DNA was extracted from the fossil termite Mastotermes electrodominicus preserved in Oligo-Miocene amber (25 million to 30 million years old). Fragments of mitochondrial [16S ribosomal DNA (rDNA)] and nuclear (18S rDNA) genes were amplified by polymerase chain reaction. Phylogenetic analysis of fossil and extant 18S rDNA confirmed morphological cladistic analyses of living dictyopterans (termites, cockroaches, and mantids). The fossil termite shares several sequence attributes with Mastotermes darwiniensis. Addition of this fossil to living-species phylogeny is required to substantiate Mastotermes monophyly and affects molecular phylogenetic hypotheses of termites in this, the oldest DNA yet characterized. PMID- 1411509 TI - Measurement of quantum tunneling between chiral isomers of the cyclic water trimer. AB - A detailed experimental study of the water trimer is reported. A vibration rotation-tunneling band of the perdeuterated cluster has been measured near 89.6 wave numbers by tunable far infrared laser absorption spectroscopy. The data indicate a chiral six-membered ring structure with rapid quantum tunneling occurring between the enantiomers. The observed vibration involves torsional motion of the water subunits about each hydrogen bond axis. It is speculated that larger water clusters would also exhibit transient chirality and that similar effects may be found in liquid water. PMID- 1411510 TI - Discovery of a peptide-based renin inhibitor with oral bioavailability and efficacy. AB - Peptidic renin inhibitors have been poorly absorbed across the intestine or rapidly eliminated by the liver and have been reported to have oral bioavailabilities of less than 2%. A peptide-based renin inhibitor, A-72517 (molecular mass of 706 daltons), was devised that has oral bioavailabilities of 8, 24, 32, and 53% in the monkey, rat, ferret, and dog, respectively. Dose related reductions in blood pressure, plasma renin activity, and plasma angiotensin II in parallel with increased plasma drug concentrations were observed after oral administration of A-72517 to conscious, salt-depleted dogs. Thus, peptide-based molecules of sizable molecular mass can be absorbed intact into the systemic circulation of animals. These findings support the potential of peptide-based drugs for oral administration. PMID- 1411511 TI - Actin filament dynamics in living glial cells imaged by atomic force microscopy. AB - Observation of filamentous actin (F-actin) in living cells is currently limited to the resolution of the light microscope. Higher resolution procedures require sample fixation and preclude dynamic studies. The atomic force microscope (AFM) can image and manipulate samples at very high, sometimes atomic resolution by scanning a fine tip over the surface of interest and detecting physical interactions between the tip and sample. This study demonstrates that F-actin can be readily resolved in living cells with the AFM and that the dynamic properties of F-actin are easily observed. PMID- 1411512 TI - Multiple zinc finger forms resulting from developmentally regulated alternative splicing of a transcription factor gene. AB - Transcripts encoding the Drosophila putative transcription factor CF2 are subject to developmentally regulated alternative splicing, and they encode protein isoforms that differ in the number of zinc fingers. One testis-specific RNA encodes an isoform that includes three zinc fingers and a frame-shifted segment. Two other transcripts encode isoforms with six and seven zinc fingers which bind to distinct promoters and DNA target sequences. Thus, because of alternative splicing, a single gene appears to encode distinct DNA-binding proteins, each capable of regulating different gene sets in different tissues and developmental periods. PMID- 1411513 TI - The dimensions of the brain. PMID- 1411514 TI - Rational science, irrational reality: a congressional perspective on basic research and society. PMID- 1411515 TI - Drugs from Third World plants: the future. PMID- 1411516 TI - NIH officials huddle with AIDS activists. PMID- 1411517 TI - R&D budget collides with the deficit. PMID- 1411518 TI - AIDS funding. Did political clout win vaccine trial for MicroGeneSys? PMID- 1411519 TI - HHS 'violence initiative' caught in a crossfire. PMID- 1411520 TI - The brain remaps its own contours. PMID- 1411521 TI - Spinal cord injuries. New optimism blooms for developing treatments. PMID- 1411522 TI - Are adult learning mechanisms also used for development? PMID- 1411523 TI - The physiology of memory: recordings of things past. PMID- 1411524 TI - Rodent carcinogens: setting priorities. AB - The human diet contains an enormous background of natural chemicals, such as plant pesticides and the products of cooking, that have not been a focus of carcinogenicity testing. A broadened perspective that includes these natural chemicals is necessary. A comparison of possible hazards for 80 daily exposures to rodent carcinogens from a variety of sources is presented, using an index (HERP) that relates human exposure to carcinogenic potency in rodents. A similar ordering would be expected with the use of standard risk assessment methodology for the same human exposure values. Results indicate that, when viewed against the large background of naturally occurring carcinogens in typical portions of common foods, the residues of synthetic pesticides or environmental pollutants rank low. A similar result is obtained in a separate comparison of 32 average daily exposures to natural pesticides and synthetic pesticide residues in the diet. Although the findings do not indicate that these natural dietary carcinogens are important in human cancer, they cast doubt on the relative importance for human cancer of low-dose exposures to synthetic chemicals. PMID- 1411525 TI - X-ray laser microscopy of rat sperm nuclei. AB - The development of high brightness and short pulse width (< 200 picoseconds) x ray lasers now offers biologists the possibility of high-resolution imaging of specimens in an aqueous environment without the blurring effects associated with natural motions and chemical erosion. As a step toward developing the capabilities of this type of x-ray microscopy, a tantalum x-ray laser at 44.83 angstrom wavelength was used together with an x-ray zone plate lens to image both unlabeled and selectively gold-labeled dried rat sperm nuclei. The observed images show approximately 500 angstrom features, illustrate the importance of x ray microscopy in determining chemical composition, and provide information about the uniformity of sperm chromatin organization and the extent of sperm chromatin hydration. PMID- 1411526 TI - Intercellular propagation of calcium waves mediated by inositol trisphosphate. AB - Two types of calcium (Ca2+) signaling-propagating intercellular Ca2+ waves of increasing intracellular Ca2+ concentration ([Ca2+]i) and nonpropagating oscillations in [Ca2+]i-co-exist in a variety of cell types. To investigate this difference in Ca2+ signaling, airway epithelial cells were loaded with heparin, an inositol 1,4,5-triphosphate (IP3) receptor antagonist, by pulsed, high frequency electroporation. Heparin inhibited propagation of intercellular Ca2+ waves but not oscillations of [Ca2+]i. In heparin-free cells, Ca2+ waves propagated through cells displaying [Ca2+]i oscillations. Depletion of intracellular Ca2+ pools with the Ca2+-pump inhibitor thapsigargin also inhibited the propagation of Ca2+ waves. These studies demonstrate that the release of Ca2+ by IP3 is necessary for the propagation of intercellular Ca2+ waves and suggest that IP3 moves through gap junctions to communicate intercellular Ca2+ waves. PMID- 1411527 TI - Diverse migratory pathways in the developing cerebral cortex. AB - During early development of the mammalian cerebral cortex, young neurons migrate outward from the site of their final mitosis in the ventricular zone into the cortical plate, where they form the adult cortex. Time-lapse confocal microscopy was used to observe directly the dynamic behaviors of migrating cells in living slices of developing cortex. The majority of cells migrated along a radial pathway, consistent with the view that cortical neurons migrate along radial glial fibers. A fraction of cells, however, turned within the intermediate zone and migrated orthogonal to the radial fibers. This orthogonal migration may contribute to the tangential dispersion of clonally related cortical neurons. PMID- 1411528 TI - Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto oncogene. AB - Approximately half of the neurons produced during embryogenesis normally die before adulthood. Although target-derived neurotrophic factors are known to be major determinants of programmed cell death--apoptosis--the molecular mechanisms by which trophic factors interfere with cell death regulation are largely unknown. Overexpression of the bcl-2 proto-oncogene in cultured sympathetic neurons has now been shown to prevent apoptosis normally induced by deprivation of nerve growth factor. This finding, together with the previous demonstration of bcl-2 expression in the nervous system, suggests that the Bcl-2 protein may be a major mediator of the effects of neurotrophic factors on neuronal survival. PMID- 1411529 TI - Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. AB - Altered processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease. To investigate whether cellular APP processing is controlled by cell surface neurotransmitter receptors, human embryonic kidney (293) cell lines were transfected with the genes for human brain muscarinic acetylcholine receptors. Stimulation of m1 and m3 receptor subtypes with carbachol increased the basal release of APP derivatives within minutes of treatment, indicating that preexisting APP is released in response to receptor activation. Receptor activated APP release was blocked by staurosporine, suggesting that protein kinases mediate neurotransmitter receptor-controlled APP processing. PMID- 1411531 TI - Use of animal drugs. PMID- 1411530 TI - The dispersion of neuronal clones across the cerebral cortex. PMID- 1411532 TI - Science policy: the candidates' response. PMID- 1411533 TI - Radiation risks. Study casts doubt on Hiroshima data. PMID- 1411534 TI - Mortality: overturning received wisdom. PMID- 1411535 TI - E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. AB - The cellular transcription factor E2F, previously identified as a component of early adenovirus transcription, has now been shown to be important in cell proliferation control. E2F appears to be a functional target for the action of the tumor suppressor protein Rb that is encoded by the retinoblastoma susceptibility gene. The disruption of this E2F-Rb interaction, as well as a complex involving E2F in association with the cell cycle-regulated cyclin A-cdk2 kinase complex, may be a common mechanism of action for the oncoproteins encoded by the DNA tumor viruses. PMID- 1411536 TI - Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III. AB - The crystal structure of the DNA repair enzyme endonuclease III, which recognizes and cleaves DNA at damaged bases, has been solved to 2.0 angstrom resolution with an R factor of 0.185. This iron-sulfur [4Fe-4S] enzyme is elongated and bilobal with a deep cleft separating two similarly sized domains: a novel, sequence continuous, six-helix domain (residues 22 to 132) and a Greek-key, four-helix domain formed by the amino-terminal and three carboxyl-terminal helices (residues 1 to 21 and 133 to 211) together with the [4Fe-4S] cluster. The cluster is bound entirely within the carboxyl-terminal loop with a ligation pattern (Cys-X6-Cys-X2 Cys-X5-Cys) distinct from all other known [4Fe-4S] proteins. Sequence conservation and the positive electrostatic potential of conserved regions identify a surface suitable for binding duplex B-DNA across the long axis of the enzyme, matching a 46 angstrom length of protected DNA. The primary role of the [4Fe-4S] cluster appears to involve positioning conserved basic residues for interaction with the DNA phosphate backbone. The crystallographically identified inhibitor binding region, which recognizes the damaged base thymine glycol, is a seven-residue beta-hairpin (residues 113 to 119). Location and side chain orientation at the base of the inhibitor binding site implicate Glu112 in the N glycosylase mechanism and Lys120 in the beta-elimination mechanism. Overall, the structure reveals an unusual fold and a new biological function for [4Fe-4S] clusters and provides a structural basis for studying recognition of damaged DNA and the N-glycosylase and apurinic/apyrimidinic-lyase mechanisms. PMID- 1411537 TI - Small-angle synchrotron x-ray scattering reveals distinct shape changes of the myosin head during hydrolysis of ATP. AB - In the energy transduction of muscle contraction, it is important to know the nature and extent of conformational changes of the head portion of the myosin molecules. In the presence of magnesium adenosine triphosphate (MgATP), fairly large conformational changes of the myosin head [subfragment-1 (S1)] in solution were observed by small-angle x-ray scattering with the use of synchrotron radiation as an intense and stable x-ray source. The presence of MgATP reduced the radius of gyration of the molecule by about 3 angstrom units and the maximum chord length by about 10 angstroms, showing that the shape of S1 becomes more compact or round during hydrolysis of MgATP. Comparison with various nucleotide bound S1 complexes that correspond to the known intermediate states during ATP hydrolysis indicates that the shape of S1 in a key intermediate state, S1-bound adenosine diphosphate (ADP) and phosphate [S1**.ADP.P(i)], differs significantly from the shape in the other intermediate states of the S1 adenosine triphosphatase cycle as well as that of nucleotide-free S1. PMID- 1411538 TI - Neural computing in cancer drug development: predicting mechanism of action. AB - Described here are neural networks capable of predicting a drug's mechanism of action from its pattern of activity against a panel of 60 malignant cell lines in the National Cancer Institute's drug screening program. Given six possible classes of mechanism, the network misses the correct category for only 12 out of 141 agents (8.5 percent), whereas linear discriminant analysis, a standard statistical technique, misses 20 out of 141 (14.2 percent). The success of the neural net indicates several things. (i) The cell line response patterns are rich in information about mechanism. (ii) Appropriately designed neural networks can make effective use of that information. (iii) Trained networks can be used to classify prospectively the more than 10,000 agents per year tested by the screening program. Related networks, in combination with classical statistical tools, will help in a variety of ways to move new anticancer agents through the pipeline from in vitro studies to clinical application. PMID- 1411539 TI - Some anthropological aspects of the prehistoric Tyrolean ice man. AB - The corpse of a Late Neolithic individual found in a glacier in Oetztal is unusual because of the intact nature of all body parts that resulted from the characteristics of its mummification process and its protected geographical position with regard to glacier flow. Anthropological data indicate that the man was 25 to 40 years old, was between 156 and 160 centimeters in stature, had a cranial capacity of between 1500 and 1560 cubic centimeters, and likely died of exhaustion. PMID- 1411540 TI - Slowing of mortality rates at older ages in large medfly cohorts. AB - It is generally assumed for most species that mortality rates increase monotonically at advanced ages. Mortality rates were found to level off and decrease at older ages in a population of 1.2 million medflies maintained in cages of 7,200 and in a group of approximately 48,000 adults maintained in solitary confinement. Thus, life expectancy in older individuals increased rather than decreased with age. These results cast doubt on several central concepts in gerontology and the biology of aging: (i) that senescence can be characterized by an increase in age-specific mortality, (ii) that the basic pattern of mortality in nearly all species follows the same unitary pattern at older ages, and (iii) that species have absolute life-span limits. PMID- 1411541 TI - Demography of genotypes: failure of the limited life-span paradigm in Drosophila melanogaster. AB - Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest age. PMID- 1411542 TI - Absorption spectra of the hybrid pigments responsible for anomalous color vision. AB - Unequal homologous recombination events between green and red cone pigment genes produce the red-green or green-red hybrid pigment genes found in many individuals with variant color vision. Photobleaching difference absorption spectroscopy of hybrid pigments produced in cultured cells shows that the spectral sensitivity of each hybrid pigment is intermediate between the parental green and red pigment sensitivities. Amino acids encoded by exons 2, 3, 4, and 5 produce spectral shifts at the wavelength of maximal absorbance of 0 to 4, 0 to 4, 3 to 4, and 15 to 21 nanometers, respectively, the exact value depending on the identities of amino acids elsewhere in the hybrid. PMID- 1411543 TI - Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. AB - Apolipoprotein E (apoE) is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins. Lack of apoE is, therefore, expected to cause accumulation in plasma of cholesterol-rich remnants whose prolonged circulation should be atherogenic. ApoE-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis. The mutant mice had five times normal plasma cholesterol, and developed foam cell-rich depositions in their proximal aortas by age 3 months. These spontaneous lesions progressed and caused severe occlusion of the coronary artery ostium by 8 months. The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process. PMID- 1411544 TI - Formation of a gated channel by a ligand-specific transport protein in the bacterial outer membrane. AB - The ferric enterobactin receptor (FepA) is a high-affinity ligand-specific transport protein in the outer membrane of Gram-negative bacteria. Deletion of the cell-surface ligand-binding peptides of FepA generated mutant proteins that were incapable of high-affinity uptake but that instead formed nonspecific, passive channels in the outer membrane. Unlike native FepA, these pores acted independently of the accessory protein TonB, which suggests that FepA is a gated porin and that TonB acts as its gatekeeper by facilitating the entry of ligands into the FepA channel. The sequence homology among TonB-dependent proteins suggests that all ligand-specific outer membrane receptors may function by this gated-porin mechanism. PMID- 1411545 TI - DNA polymerase beta and DNA synthesis in Xenopus oocytes and in a nuclear extract. AB - The identities of the DNA polymerases required for conversion of single-strand (ss) M13 DNA to double-strand (ds) M13 DNA were examined both in injected Xenopus laevis oocytes and in an oocyte nuclear extract. Inhibitors and antibodies specific to DNA polymerases alpha and beta were used. In nuclear extracts, inhibition by the antibody to polymerase beta could be reversed by purified polymerase beta. The polymerase beta inhibitors, dideoxythymidine triphosphate (ddTTP) and dideoxycytidine triphosphate (ddCTP), also blocked DNA synthesis and indicated that polymerase beta is involved in the conversion of ssDNA to dsDNA. These results also may have particular significance for emerging evidence of an ssDNA replication mode in eukaryotic cells. PMID- 1411546 TI - The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. AB - Mitogen-activated protein (MAP) kinases, also known as extracellular signal regulated kinases (ERKs), are thought to act at an integration point for multiple biochemical signals because they are activated by a wide variety of extracellular signals, rapidly phosphorylated on threonine and tyrosine, and highly conserved. A critical protein kinase lies upstream of MAP kinase and stimulates the enzymatic activity of MAP kinase. The structure of this protein kinase, denoted MEK1, for MAP kinase or ERK kinase, was elucidated from a complementary DNA sequence and shown to be a protein of 393 amino acids (43,500 daltons) that is related most closely in size and sequence to the product encoded by the Schizosaccharomyces pombe byr1 gene. The MEK gene was highly expressed in murine brain, and the product expressed in bacteria phosphorylated the ERK gene product. PMID- 1411547 TI - Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. AB - Double-strand breaks (DSBs) in Saccharomyces cerevisiae can be repaired by gene conversions or by deletions resulting from single-strand annealing between direct repeats of homologous sequences. Although rad1 mutants are resistant to x-rays and can complete DSB-mediated mating-type switching, they could not complete recombination when the ends of the break contained approximately 60 base pairs of nonhomology. Recombination was restored when the ends of the break were made homologous to donor sequences. Additionally, the absence of RAD1 led to the frequent appearance of a previously unobserved type of recombination product. These data suggest RAD1 is required to remove nonhomologous DNA from the 3' ends of recombining DNA, a process analogous to the excision of photodimers during repair of ultraviolet-damaged DNA. PMID- 1411548 TI - Interaction of the immunosuppressant deoxyspergualin with a member of the Hsp70 family of heat shock proteins. AB - Deoxyspergualin (DSG) is a potent immunosuppressant whose mechanism of action remains unknown. To elucidate its mechanism of action, an intracellular DSG binding protein was identified. DSG has now been shown to bind specifically to Hsc70, the constitutive or cognate member of the heat shock protein 70 (Hsp70) protein family. The members of the Hsp70 family of heat shock proteins are important for many cellular processes, including immune responses, and this finding suggests that heat shock proteins may represent a class of immunosuppressant binding proteins, or immunophilins, distinct from the previously identified cis-trans proline isomerases. DSG may provide a tool for understanding the function of heat shock proteins in immunological processes. PMID- 1411549 TI - The readers' NIH. PMID- 1411550 TI - The readers' NIH. PMID- 1411551 TI - The readers' NIH. PMID- 1411552 TI - The readers' NIH. PMID- 1411553 TI - The readers' NIH. PMID- 1411554 TI - The readers' NIH. PMID- 1411555 TI - The readers' NIH. PMID- 1411556 TI - The readers' NIH. PMID- 1411557 TI - The readers' NIH. PMID- 1411559 TI - The readers' NIH. PMID- 1411558 TI - The readers' NIH. PMID- 1411560 TI - The readers NIH. PMID- 1411561 TI - The readers NIH. PMID- 1411562 TI - The readers' NIH. PMID- 1411563 TI - Lobbying for an AIDS trial. PMID- 1411564 TI - Medicine: a signal contribution to cell biology. PMID- 1411565 TI - Biology: there's honor outside Stockholm. PMID- 1411566 TI - Familial Alzheimer's linked to chromosome 14 gene. PMID- 1411567 TI - Profiles. Diversity flourishes in Japan's research labs. AB - Japan may look homogenous but the pace of change has actually created a people of extraordinary diversity. Scientists educated before the war at the elite "Imperial" universities are different from those born a few years later; those who experienced postwar poverty are not the same as those born into riches a little later; researchers in wealthy industrial labs see the world differently from their poorer colleagues at the universities; and scientists who have lived abroad for a long while change their perceptions for ever. Below, Science talks to Japanese scientists of different ages and different experiences in a wide variety of disciplines: Among them are a Nobel Prize--winner, an ex-student radical, one of Japan's most powerful scientific leaders, an eccentric genius- and some older people who remember Japan's problems and younger people who see Japan's opportunities. PMID- 1411568 TI - Early cultivators of science in Japan. PMID- 1411569 TI - Interleukin-6 and its receptor: a paradigm for cytokines. AB - Many cytokines and cytokine receptors involved in the regulation of hematopoiesis, immune responses, and inflammation have been identified and characterized at the molecular level. Several characteristic features of cytokines, such as pleiotropy and redundancy, are now more clearly understood on the basis of their molecular structures. Accumulating evidence has demonstrated an intimate link between cytokines and various diseases such as allergy, autoimmune diseases, and cancer. The pathogenesis of these diseases and therapies to treat them will be discussed based on insights derived from cytokine research. PMID- 1411570 TI - Multistep carcinogenesis: a 1992 perspective. AB - Cancer is the leading cause of death in Japan. Recent changes in cancer incidence patterns may reflect the trend toward a more Western diet and life-style. Among the dietary factors that contribute to carcinogenesis are the heterocyclic amines, a group of mutagenic compounds present in cooked meat and fish. Carcinogenesis is a multistep process in which cells accumulate multiple genetic alterations as they progress to a more malignant phenotype. Recognition of the growing number of interacting factors that contribute to carcinogenesis may force reconsideration of current methods of risk assessment. PMID- 1411571 TI - Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. AB - Hydrolysis of inositol phospholipids by phospholipase C is initiated by either receptor stimulation or opening of Ca2+ channels. This was once thought to be the sole mechanism to produce the diacylglycerol that links extracellular signals to intracellular events through activation of protein kinase C. It is becoming clear that agonist-induced hydrolysis of other membrane phospholipids, particularly choline phospholipids, by phospholipase D and phospholipase A2 may also take part in cell signaling. The products of hydrolysis of these phospholipids may enhance and prolong the activation of protein kinase C. Such prolonged activation of protein kinase C is essential for long-term cellular responses such as cell proliferation and differentiation. PMID- 1411572 TI - The economics of health care in Japan. AB - Japan's health care system balances universal coverage at reasonable cost. The government has taken on the responsibility of acting as insurer and subsidizing health care spending for the employees of small enterprises and the self employed. Despite the fee-for-service form of payment, costs have been contained by the use of a nationally uniform fee schedule that is mandatory for all providers. However, the increasingly affluent and aging population is making new demands on the system that can only be met by a major restructuring. PMID- 1411573 TI - A priori evaluation of aqueous polarization effects through Monte Carlo QM-MM simulations. AB - A Monte Carlo quantum mechanical-molecular mechanical (QM-MM) simulation method was used to determine the contributions of the solvent polarization effect to the total interaction energies between solute and solvent for amino acid side chains and nucleotide bases in aqueous solution. In the present AM1-TIP3P approach, the solute molecule is characterized by valence electrons and nucleus cores with Hartree-Fock theory incorporating explicit solvent effects into the total Hamiltonian, while the solvent is approximated by the three-point charge TIP3P model. The polarization energy contributes 10 to 20 percent of the total electrostatic energy in these systems. The performance of the hybrid AM1-TIP3P model was further validated by consideration of bimolecular complexes with water and by computation of the free energies of solvation of organic molecules using statistical perturbation theory. Excellent agreement with ab initio 6-31G(d) results and experimental solvation free energies was obtained. PMID- 1411574 TI - Hemoglobin-AGE: a circulating marker of advanced glycosylation. AB - Advanced glycosylation end products (AGEs) form spontaneously from glucose derived Amadori products and accumulate on long-lived tissue proteins. AGEs have been implicated in the pathogenesis of several of the complications of aging and diabetes, including atherosclerosis and renal disease. With the use of recently developed AGE-specific antibodies, an AGE-modified form of human hemoglobin has been identified. Termed hemoglobin-AGE (Hb-AGE), this modified species accounts for 0.42 percent of circulating hemoglobin in normal individuals but increases to 0.75 percent in patients with diabetes-induced hyperglycemia. In a group of diabetic patients treated with the advanced glycosylation inhibitor aminoguanidine, Hb-AGE levels decreased significantly over a 1-month period. Hemoglobin-AGE measurements may provide an index of long-term tissue modification by AGEs and prove useful in assessing the contribution of advanced glycosylation to a variety of diabetic and age-related complications. PMID- 1411575 TI - Phase coupling by synaptic spread in chains of coupled neuronal oscillators. AB - Many neural systems behave as arrays of coupled oscillators, with characteristic phase coupling. For example, the rhythmic activation patterns giving rise to swimming in fish are characterized by a rostral-to-caudal phase delay in ventral root activity that is independent of the cycle duration. This produces a traveling wave of curvature along the body of the animal with a wavelength approximately equal to the body length. Here a simple mechanism for phase coupling in chains of equally activated oscillators is postulated: the synapses between the cells making up a "unit oscillator" are simply repeated in neighboring segments, with a reduced synaptic strength. If such coupling is asymmetric in the rostral and caudal directions, traveling waves of activity are produced. The intersegmental phase lag that develops is independent of the coupling strength over at least a tenfold range. Furthermore, for the unit oscillator believed to underlie central pattern generation in the lamprey spinal cord, such coupling can result in a phase lag that is independent of frequency. PMID- 1411576 TI - Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14. AB - Linkage analysis was used to search the genome for chromosomal regions harboring familial Alzheimer's disease genes. Markers on chromosome 14 gave highly significant positive lod scores in early-onset non-Volga German kindreds; a Zmax of 9.15 (theta = 0.01) was obtained with the marker D14S43 at 14q24.3. One early onset family yielded a lod score of 4.89 (theta = 0.0). When no assumptions were made about age-dependent penetrance, significant results were still obtained (Zmax = 5.94, theta = 0.0), despite the loss of power to detect linkage under these conditions. Results for the Volga German families were either negative or nonsignificant for markers in this region. Thus, evidence indicates a familial Alzheimer's disease locus on chromosome 14. PMID- 1411577 TI - Sarcoidosis in autoimmune disease. AB - Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Sarcoidosis coexisting with connective tissue diseases, once considered rare, complicates various such disorders, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, and the spondyloarthropathies. Symptoms common to sarcoidosis and autoimmune disease include keratoconjunctivitis sicca, weight loss, fever, lymphadenopathy, pulmonary complaints, and cutaneous lesions. Consequently, the diagnosis of sarcoidosis in association with connective tissue disease is often difficult and may require biopsy of the lung, liver, skin, lymph node, muscle, or bone marrow for pathological confirmation. Abnormalities of immune function as well as autoantibody production, including rheumatoid factor and antinuclear antibodies, are seen in sarcoidosis and in connective tissue diseases, suggesting a common immunopathogenic mechanism. The severity and course of sarcoidosis associated with autoimmune disease is variable. The incidence of sarcoidosis in association with rheumatic disease may be underestimated if new symptoms of sarcoidosis are attributed to the primary rheumatic disease and a secondary diagnosis is not pursued. PMID- 1411578 TI - Cryptococcal meningitis in systemic lupus erythematosus. AB - Two cases of cryptococcal meningitis occurring in patients with systemic lupus erythematosus (SLE) are presented, and 24 additional cases from the literature are reviewed. The insidious onset of this infrequent complication is emphasized. The nonspecific neurological findings associated with this infection are often mistakenly diagnosed as a central nervous system manifestation of SLE. Earlier diagnosis and effective antifungal therapy have improved the prognosis of cryptococcal meningitis in SLE patients in recent years. Strategies for the treatment of patients with this complication are discussed. PMID- 1411579 TI - Septic subdeltoid bursitis. AB - Four cases of septic subdeltoid bursitis are described. Clinical presentations, microbiology, and therapies are reviewed for these cases as well as for the six previously reported cases in the literature. The etiology of septic subdeltoid bursitis was related to bacteremia, trauma, or immune incompetence. Compared with septic oelcranon and prepatellar bursitis, septic subdeltoid bursitis was associated with a more profound inflammatory reaction in the bursa, required more sophisticated diagnostic imaging, and necessitated more aggressive therapy. Appropriate therapy generally resulted in favorable outcomes. PMID- 1411580 TI - Cyclosporine in rheumatoid arthritis. AB - The efficacy and toxicity of cyclosporine in the treatment of patients with rheumatoid arthritis (RA) are reviewed. Most of the early trials were restricted to patients with intractable RA. The initial daily dose of cyclosporine was 5 to 10 mg/kg, which is now considered high. Of 283 cyclosporine-treated patients in nine studies, 8% discontinued the drug prematurely because of inefficacy and 17% because of adverse reactions. Cyclosporine improves clinical parameters but does not influence the erythrocyte sedimentation rate. The most important side effects are gastrointestinal intolerance and nephrotoxicity. The former is of minor importance with the present dosage schedule (starting daily dose, 2.5 mg/kg), and increments should follow the principle "go low, go slow." Guidelines are given to avoid or reduce nephrotoxicity. It may be beneficial to administer cyclosporine early in the course of RA. PMID- 1411581 TI - Collagenase in synovitis of rheumatoid arthritis. AB - There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP 1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue. PMID- 1411582 TI - Light and electron microscopic observations on the synovitis of ankylosing spondylitis. AB - Light microscopic studies on synovium obtained from seven knees and three hips of patients with ankylosing spondylitis and peripheral arthritis showed surface fibrin, proliferation of synovial lining cells, moderate infiltration with lymphocytes, and sometimes striking numbers of plasma cells. There was some vascular congestion and obliteration, occasional bone and cartilage debris, and a tendency toward increased fibrous tissue. Although the intensity of some findings varies from those in rheumatoid arthritis, there were no consistent distinguishing features. Electron microscopy of eight synovial tissue specimens showed increased type B or synthetic lining cells. Structures that could possibly have been organisms were seen among synovial cells in two patients. Immune complex-like deposits were not seen in vessel walls, although there were other vascular alterations. Synovial fluid studies showed 2,200 to 16,500 white blood cells/mm3 (mean, 8,236), 29% to 93% polymorphonuclear leukocytes (mean, 66%), and 0.5 to 32% lymphocytes (mean, 18%). The presence of at least some activated lymphocytes (lymphoblasts) in seven of nine patients in addition to the above findings in synovium suggest an immunological component to the driven process. No more than 32% lymphocytes was found in any synovial fluid despite the use of nonsteroidal antiinflammatory drugs. Thus no support for synovial fluid lymphocytosis, such as has been described in rheumatoid arthritis patients treated with nonsteroidal antiinflammatory drugs alone, is provided. PMID- 1411583 TI - [Defects in canalization of seminal pathways]. AB - We assessed the value of ultra sonography in diagnosis and grading the alterations in canalization of seminal pathways. After clinical examination and semen analysis, we studied 4100 patients by scrotal US with sector mechanical (7.5 MHz) probe with water bag and by transrectal US for prostatic vesicular region evaluation with 5-6.5 MHz linear probe (lately we used biplanar probe). In three cases, we performed us guided aspiration and contrast media injection of prostatic cavity. In 63 cases (1.53%) we found developmental malformations of seminal vesicles. The abnormality was bilaterally in 33% and it was associated with malformations of urinary tract in 17.46%. Other malformations were found in 0.12% cases. Ultrasonography was always able to establish obstruction level and type, and the possible associated abnormalities. US permitted to avoid or to restrict testis biopsy or vasoseminal vesiculogram. Ultrasonography is eventually able to guide second level diagnostic examination (aspiration biopsy and contrast media injection of prostatic cysts) and endourethral approach to drainage. PMID- 1411584 TI - [Ultrasound-color Doppler in the study of sexual impotence]. AB - Male impotence is a relatively frequency disease. To define the correct aetiology of this disorder is important to plan a right diagnosis to difference organic, psychological and psycho-organic causes. From June 90 to June 91 fifty-four patients with male impotence of different degree were observed and went through diagnostic investigations. The patients were classified in four groups (A, B, C, D) as clinical results of the pharmacological test (intracavernous injection of PGE1 alpha 15 micrograms). A and B groups showed normal and nearly normal hemogenic finding. C group showed either low arterial flow increase after FIC or venous leakage. D group showed very low haemodynamic increase. The analysis of Eco-doppler studies was performed 5'-10'-20' after intracavernous injection of PGE1 alpha obtaining three haemodynamic markers: the systolic top flow (Vs) the diastolic ending flow (Vd) resistance flow index. The Authors discuss the results obtained considering the Eco-color-doppler the most important stage in the haemodynamic evaluation of sexual impotence. PMID- 1411585 TI - [Extrarenal ultrasound and color Doppler: renal artery stenosis]. AB - There is a long term interest in noninvasive Doppler (Duplex Doppler, Color Doppler) methods to screen patients with reno-vascular hypertension resistant to medical therapy. Doppler criteria for the diagnosis of renal artery stenosis in native kidneys vary (peak systolic velocity exceeding 100 cm/sec; RAR (Renal Aortic Ratio) exceeding 3.5; Doppler shift frequency exceeding 6-8 KHz; dampened peripheral waveform; lack of signal in complete occlusion). When the vessels are adequately visualized (about 40% of cases) sensitivity and specificity are quite good (80-90%). In the transplanted kidney Doppler diagnosis of renal artery is easier (diagnostic accuracy about 90%). The diagnostic criteria have been well codified (Doppler shift of 7.5 KHz at an insonating frequency of 3 MHz). PMID- 1411586 TI - [Ultrasound and color Doppler control of percutaneous angioplasty (PTA) of the renal artery]. AB - The Authors report their experience about fifty patients affected with renovascular hypertension, treated by percutaneous transluminal angioplasty (PTA) for stenosis of main renal artery and now studied by Duplex-Scan and Color doppler. Results, compared with arterial pressure measurements, renography and laboratory renal function evaluation, showed a sensibility of 84%, specificity of 90% and an accuracy of 87.5%. Advantages and limits of Duplex-scan in patients treated by PTA are briefly discussed. PMID- 1411587 TI - [The role of nuclear medicine in renovascular pathology of urologic significance]. AB - The diagnostic contribution of the radiological techniques (intravenous urography, angiography, sonography, computer tomography) is well-known. On the contrary, in this field, the possibilities of the Nuclear Medicine are underestimated. Radiological methods have high detail recognition but are only suitable for assessing the functional significance of morphological changes in a restricted sense; in the last 25 years, nuclear medical renal diagnosis has achieved a differentiated development stage which permits new qualitative and quantitative tests. The radioisotopic methods offer morphological informations which surely are less exact than those given by radiological techniques, on the other hand they add irreplaceable parameters of functional significance; these parameters concern the perfusion and the accumulation and excretion constants of selected areas of interest in renal districts. This is made possible by a wide choice of radiopharmaceuticals, having a different dynamic pattern and biodistribution. The Authors consider scintigraphic imaging of different renal pathologies: trauma, characterized by hypoperfusion; hematoma and/or urinoma; pseudotumor and carcinoma. Nuclear medical techniques allow in nearly all the cases a rapid and exact diagnostic guidance. The AA. emphasize the absence of invasiveness, the simplicity and the good compliance of these methods in all patients, even if seriously ill, and the usefulness in follow-up and diagnosis of several pathological conditions. Finally, they underline the absence of an appreciable radiobiological hazard. PMID- 1411588 TI - [Intra-renal ultrasound and color Doppler: pathology or nephrologic significance]. AB - Us-Doppler examination of the native kidney gives more detailed information on nephrological vascular disease. Since there is a close connection between renal functional units (nephrons) and vascular and interstitial compartments, alterations in intrarenal flow will obviously occur in all types of medical nephropathy, irrespective of the origin of the anatomopathological damage. Altered intrarenal flow occur with increased vascular impedance, in turn related to an increased resistance index (RI). In nephropathy with dilatation, the RI can distinguish obstructive from non-obstructive dilatation (high and normal RI, respectively). Personal experience of 80 kidneys with nonobstructive medical nephropathy has shown a good correlation between increased RI and deterioration of renal function, demonstrating that, renal function being equal, RI is higher in Vascular than Tubulo-interstitial and Glomerular nephropathies. For medical nephropathy of transplanted kidneys, Us-Doppler evaluation can be combined with conventional Doppler for diagnosing acute rejection. In this series, an elevated RI (0.90) is highly predictive of acute rejection (92% specificity) but has low sensitivity (30%). At the threshold value of RI = 0.80, sensitivity is 66% and specificity is 78%. However, it is considered that far more reliable information is obtained if Doppler examination is combined with conventional U.S. morphology. PMID- 1411589 TI - [Integration of diagnostic methods in renal vascular pathology]. AB - Modern technology allows us to study the renal vascular diseases by means of many diagnostic procedures. In the past the main diagnostic technique was Urography, whereas Angiography were performed only in few selected cases. The new Imaging Techniques totally changed the diagnostic approach to this kind of diseases. Today in fact Echo-Color-Doppler and Nuclear Medicine are the early diagnostic techniques to be performed. Actually only few selected patients undergo Angiography, not the conventional one but the Digital; this new technique, in fact, in case of renovascular Hypertension is not only of diagnostic value but is often the definitive therapy. PMID- 1411590 TI - [Diagnostic imaging in renal vascular diseases: old and new ways. Role of nuclear medicine]. AB - Using the nuclear medicine procedures it is possible to evaluate the renovascular hypertension via the captopril test. Decreased renal blood flow due to stenotic vessel may produce a variety of findings on the renogram using both OIH-I131 and DTPA-Tc99m. Delayed transit time and excretion also may be detected. In this situation the sensitivity and specificity of Nuclear Medicine for RAS detection is very low. Using Captopril test is possible to detect enhanced modification on the shape of renogram due to Angiotensin Converting enzyme inhibition. PMID- 1411591 TI - [Vascular pathology of urologic significance: Doppler and color Doppler]. AB - The combined use of B-mode ultrasonography and doppler (p.w. and/or color doppler) provides a more accurate and detailed study of vascular pathology than B mode ultrasonography alone. In fact, besides to document the presence of blood flow and to assess its direction, doppler US provides a quantitative evaluation of blood flow. Chromatic codification of blood flow (usually red if flowing towards the probe, blue if flowing away from the probe and yellow or green in the case of turbulence) permits to assess the presence of blood flow even in areas where a vessel cannot be depicted by B-mode ultrasonography. In fact in the study of blood flow to the kidney it's possible with color-doppler to visualize not only the main renal arteries but segmental-intraparenchymal arteries too; that is very useful in the detection of rejection of allograft. In renal artery, blood flow presents a pattern of low resistance: a brief systolic phase followed by a longer diastolic one, without inversion of flow. In renal vein, blood flow is, on the contrary, continuous. The main disorders of the kidney and urinary tract, which can be detected by color doppler are the following: renal-vascular hypertension, rejection of allograft, renal vein thrombosis, portal hypertension with spleno-renal collateral channels, disorders of ureteral motility, space occupying lesions, medical nephropathies and obstructive uropathies. Sophisticated analysis of the flow pattern to the kidney with color doppler, by some doppler sonographic parameters (resistance index RI, pulsatility index PI), in these disorders adds a functional element to the traditional ultrasonographic imaging with a better characterization of the disease. PMID- 1411592 TI - [Ultrasonography in the follow-up of patients after extracorporeal shockwave lithotripsy]. AB - Extracorporeal shock wave lithotripsy (ESWL) has revolutionized treatment of urinary stones, but created new clinical situations and problems in the interpretation of which x-rays and ultrasonography have proved invaluable. This paper defined the role of ultrasound in the follow-up of patients who had undergone ESWL and assessed its advantages and limitations in evaluating the efficacy of this form of therapy and in monitoring the elimination of stone fragments. The utility of ultrasound in the diagnosis and monitoring of the complications due to ESWL has been emphasized. Finally ultrasound is a valid tool when performing those echo-guided procedures which are essential for the treatment of obstructive complications secondary to ESWL. PMID- 1411593 TI - [Role of ultrasonography in the follow-up of surgically treated patients. Upper urinary tract. Complications after conservative surgery]. AB - The Authors describe the purposes of ultrasonographic follow-up after both conservative surgery and endoscopic or endourological operations of the upper urinary tract. In these cases ultrasonography evaluates the results of normal surgery, the presence of early or late complications, and of iatrogenic lesions. The echo-patterns of deformations in the outline of the kidneys, of hematic, urinary or lymphatic collections (both retroperitoneal and intraperitoneal), of fistulas, of sclero-lipomatosis and of post-cicatrization hydronephrosis are described. The importance of evaluating the degree of obstruction by a dynamic ultrasonographic study with furosemide-test is emphasized. The ultrasonographic monitoring of urethral and pyelostomy setting of catheters is also described. The echo-patterns of retroperitoneal and intraperitoneal fluid collections and renal hematomas, in relation also the kind of fluid contained are widely discussed. PMID- 1411594 TI - [Radical prostatectomy: role of ultrasonography in the follow-up]. AB - After a brief summary about surgical technique of radical prostatectomy and its indications in the different stages of prostatic cancer, the Authors describe complications and surgical sequelae of this operation. The Authors report a brief series. It is composed with 13 patients. Their have been submitted to radical prostatectomy for prostatic cancer between January 1989 and September 1991. Pathological stage was B1 in 6 patients, B2 in 2 patients, C1 in 4 cases and C2 in 1. Particularly the role of ultrasonography in detection and follow-up of early complications such as lymphocele, pelvic hematoma and anastomotic urine leakage is stressed. Transrectal ultrasound is especially useful in the detection of urine leakage from vesico-urethral anastomosis. This technique is compared with traditional cystourethrography and advantages and disadvantages of the two techniques are discussed. Later complications of radical prostatectomy are anastomotic stenosis, pelvic recurrences, nodal or parenchymal metastasis, urinary incontinence. The role of transrectal ultrasound in the detection of anastomotic strictures is stressed, especially when the study is done during micturition. Transrectal ultrasound is not so satisfying in the detection of pelvic recurrences, especially if they are smaller than 1 cm. In case of large masses digital examination is diagnostic itself. At last the Authors describe urinary incontinence and its etiology as a complication of radical prostatectomy. Particularly a surgical technique for vesico-urethral anastomosis proposed by Rocca Rossetti and its value in post-operative continence is described. The Authors show the results of transrectal ultrasound in the detection of striated urethral sphincter and its function after radical prostatectomy. PMID- 1411595 TI - [Use of ultrasonography in morphofunctional evaluation of orthotopic neo bladder]. AB - Seventeen patients submitted to radical cystectomy and orthotopic bladder replacement according to Reddy's technique were studied at the 1, 3, 6 and 12 month, then annually follow-up by physical examination, intravenous pyelogram, cystourethrography, suprapubic and transrectal ultrasonography and complete urodynamics. Sixteen patients (94%) reported day-time urinary continence and twelve patients (70%) day-time and nocturnal continence. Cysto-manometry showed a mean bladder capacity of 450 cc with a maximal endocavitary pressure of 40 cm. H2O and satisfactory peak flow rate. Vesico-ureteral reflux was never detected at roentgenography. Ultrasonography may be useful in the study of a possible reflux or stenosis of the neovesico-ureteral junction by detecting renal scars or dilatation of the renal cavities. Sovrapubic ultrasonography can quantify the capacity of the neo-bladder (300-600 cc), study its shape, walls and contractions that do not cause the involuntary opening of the neo-bladder neck. Transrectal ultrasonography studies the bladder neck shape and its dynamic function. Residual urine volume never exceeded 50 cc. Ultrasonography demonstrated its effectiveness and reliability and limited the application of more invasive roentgenographic procedures. PMID- 1411596 TI - [Circumvallate nephro-cystostomy]. AB - Circumvallate nephro-cystostomy (CNC) provides a subcutaneous connection of a nephrostomy and a cystostomy catheter thus allowing spontaneous micturition. This procedure is suitable for those patients affected by an obstructive nephropathy where it was not possible to insert a double "J" stent or where surgical treatment was not allowed. Patients affected by debilitating disease benefit from these procedure by avoiding problems connected with daily handling of catheter, examples are medications at the insertion site or possible dislodgement of a nephrostomy catheter added to the psychological problems related to carry the urine collection bag. A number of 13 patients have been treated with this method, 5 had monolateral CNC, 8 had bilateral CNC for a total of 21 procedures. All but one cause of ureteral obstruction were neoplastic, the exception being a patient with necrosis of the ureter subsequent to major vascular surgery. CNC had a residence time ranging from 1, 5 to 25 months with an average of 9.8 months. Only in 2 cases it was necessary to remove CNC due to recurrent cystitis and orchitis due to bladder irritation by a cystostomy catheter and for an obstruction which could not be remedied in a patient with necrosis of the ureter. The most important complication, i.e. obstruction, occurred in 4 cases. In the above mentioned case CNC was removed after 9 months of proper performance. In the other 3 cases obstruction occurred after 2, 3, 18 months and in all this cases obstruction was easily removed. Besides obstruction only minor malfunctions were experienced and the procedure was very well tolerated by all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411597 TI - [Use of ultrasound-guided percutaneous nephrostomy before and after ESWL: 4 years of experience]. AB - We evaluated the usefulness of percutaneous nephrostomy in 1700 patients treated for reno-ureteral stones by extracorporeal shock wave lithotripsy (SWL). Out of this group 81 patients (5.8%) underwent echo-guided percutaneous nephrostomy (EPCN): the procedure has been performed in local anesthesia in 38% of the cases (31 pts) before SWL and in 62% (50 pts) after. The majority of EPCN were carried out for the presence of acute or chronic ureteral obstruction with echographic evaluable dilation of pyelocaliceal system when retrograde ureteral manipulations failed or were considered unsuitable. EPCN before SWL was performed because of ureteral stone and uncomplicated pyelocalyceal dilation (19 pts); ureteral stone, pyelocaliceal dilation and fever > 38 degrees C (3 pts); ureteral stone, pyelocalyceal dilation and functional IVP exclusion (5 pts); pyelic stone in solitary kidney (1 pts); ureteral stones in pregnancy (2 pts). EPCN after SWL was performed because of uncomplicated, persistent pile-up (31 pts); ureteral pile-up complicated by fever and colics (9 pts); ureteral obstructing fragments (2 pts); double J obstruction by stone dust (3 pts); persistent ureteral pile-up around double J (3 pts); anuria in solitary kidney (1 pt). Out of the patients who underwent EPCN before SWL 13% were stone free and without drainage at discharge, 77% had passable stone fragments at discharge and drainage has been taken out at 15-30 days check up, 10% had unbroken stone and underwent with drainage to ureterolithotripsy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411598 TI - [Endoscopic compression of bladder diverticula]. AB - The authors refer on the pathogenesis, diagnosis and therapy of bladder diverticula, with particular reference to the endoscopic compression technique performed in 35 patients. The authors stress the usefulness of bladder ultrasonography in the follow-up of operated patients. Results are comparable to those obtained cystography. PMID- 1411599 TI - [Bladder neoplasms]. AB - The authors underline the diagnostic accuracy of transurethral bladder ultrasonography in the estimation of local infiltration of bladder tumors. The study was conducted on 21 patients who underwent either endoscopic resection or cystectomy. The clinical staging obtained by transurethral echography was compared with the pathological one. The results obtained by either method were comparable in all cases. PMID- 1411600 TI - [Pathology of the spermatic cord]. AB - The purpose of this study has been to establish the role of spermatic cord in the etiopathogenesis of fertility. We describe herein the anatomy and pathology of the spermatic cord and objective method for diagnosing the disorder and evaluating the therapeutic results. The most pathological conditions affecting the cord there was a complete resolution, this condition it isn't the same for the vas deferens or varicocele. A variety of diagnostic modalities including thermography, Doppler, and particularly ultrasonography may be used to study satisfactorily. Ultrasonography technique may provide a simple but accurate non invasive method for accurately determined pathological conditions of the scrotum. It has a limited role in the management of the normal vas deferens or in congenital malformations including agenesis of vas deferens. PMID- 1411601 TI - [Duplex scanner in the diagnosis of vasculogenic impotence]. AB - This paper is reporting the experience of the Authors in the use of Duplex scanner and eco-color-doppler in the diagnosis of the erectile dysfunctions and particularly in the importance of vascular (arterious and venous) origin. For this purpose, we selected a sample constituted of 41 patients: 22 with psychogenic, 8 with arterial, 5 with venous impotence, 5 patients with Peyronie's disease and 1 patient with posttraumatic arterio-venous fistula. The Authors, while underlining the remarkable accuracy and diagnostic reliability of eco doppler, emphasize the indication of the method up to consider it "investigation of prime choice", not only in the patients with the dysfunction of vis erigendi but, in the cases in which a morphological evaluation, besides hemodynamical one, become necessary. PMID- 1411602 TI - [Selective arteriography in the study of arterial vasculogenic impotence]. AB - According to the fundamental circulatory nature of penile erection, insufficiency of the arterial blood supply to the corpora cavernosa caused by an organic arterial disease is found in a large fraction of case, overall among the patients aged more than 40. It is possible to evaluate arterial origin of erectile dysfunction by using of noninvasive methods, but to obtain the necessary panoramicity and the characterization of the lesions it needs the use of angiography. Performance of standard arteriography leads to insufficient visualization of pudendal and penile vessels and risks false positive results. Because of penile hemodynamic variability in its different states is necessary the use of pharmacologic devices to perform a diagnostic arteriography. For the selective study of the pudenda and peniena vascularization we perform a selective arteriography bilaterally, with the catheter tip placed in the proximal part of the internal iliac artery. We use a contrast medium particularly diluted and mixed with xylocaine. We perform angiographic sequences after intracavernous injection of 8-10 mgr of papaverine to obtain the maximum blood flow and to prevent spasm of the terminal arterioles. Arteriography gives a complete study of the pudenda arterial tree and its terminal ramifications, and it is able to supply all the necessary informations regarding the planning of revascularization procedures. Treatment of arterial lesions is possible with surgical and radiologic methods. As in other arteries, percutaneous transluminal angioplasty (P.T.A.) can be applied in the therapy of impotence caused by arterial insufficiency. P.T.A. is the election treatment in the stenosis of the common iliac and internal iliac arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411603 TI - [The Rigiscan system in the diagnosis of male sexual impotence]. AB - The article reviews historical basis of Nocturnal Penile Tumescence (NPT) test and the evolution of techniques to perform it. From complex and time-consuming instruments, modern technology has brought us to the use of the Rigiscan system. This is a transportable (home or office usable), computerized method to detect change of penile rigidity and circumference during sleep-related spontaneous-or daytime induced-erections. While the instrument was mainly developed to perform NPT tests, it is nowadays used to record penile rigidity in realtime after the intracavernous injection of vasoactive drugs. In our experience, normal parameters to refer for a NPT evaluation are: number of erectile episodes: 4-5 per night; mean duration od episodes: > 30 minutes; increase of penile circumference: > 3 cm (base loop) and > 2 cm (tip loop); maximal rigidity: > 70% (both base and tip). Reference parameters for realtime monitoring after intracavernous injection of PGEI are: latency of response: < 12 minutes; duration (with a stable plateau): > 30 minutes; constant plateau: > 70%; increase of penile circumference: > 3 cm (base) and > 2 cm (tip). The use of these reference parameters, together with the data coming from other procedures (e.g. penile arterial flow with the Doppler), allows a better diagnostic accuracy in the approach to sexual impotence. PMID- 1411604 TI - [Impotence: introductory notes]. AB - If we define erectile impotence as the inability to achieve and maintain a firm erection we can distinguish several pathogens of impotence: psychologic disorders, neurogenic sinusoidal disorders, arterial disorders, venous & sinusoidal disorders and systemic diseases and other disorders can cause erectile impotence. An etiologic screening of impotence must be carried out by Urologists in order to adopt the best surgical approach. Especially when surgery has to be planned, a complete, often invasive screening associated with a super-specialist diagnostic study is necessary at the beginning of any procedure. Different approaches to impotence can be adopted on the basis of patient's age, etiology and failure of other devices. The main methods of surgical correction of impotence may be divided as follows: a) percutaneous transluminal angioplasty (P.T.A.); b) revascularization; c) surgical treatment of "venous leakage", d) trans-luminal veno-occlusion (T.L.V.O.); e) correction of penile curvature; f) prostheses placement. The diagnosis of arteriogenic impotence depends upon the arteriographic demonstration of bilateral hemodynamically significant obstruction. In our experience the injection of papaverine during the test has provided a better visualization of cavernous arteries and helicine branches. Reduction of luminal diameter by more than 50% suggest a hemodynamically significant stenosis. Intracavernous injection of vasoactive agents has provided an attractive alternative to surgery. We have employed papaverine alone or with phentolamine or phenoxybenzamine. After short term treatment, some patients have achieved good erections without further injections. For P.T.A. of the distal internal pudendal arteries our approach has been via the ipsilateral or contralateral femoral arteries. Under local anesthesia a penile arteriographic catheter is placed in the internal pudendal artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411605 TI - [Role of penile ultrasonography in erection deficit]. AB - The presence of penile nodule, curvature, disorders in blood flow to and from the corpora cavernosa is often correlated with organic sexual impotence. Echography allows to obtain a clear imaging of penile structures: diameters of corpora cavernosa can be measured before and after injection of vasoactive drugs. In our study penile structure were evaluated using a Combison 310 and a Toshiba with 7.5 MHz probe. In a lot of cases echography was repeated after intracavernous injection of PGE 1 or papaverine. The equipment needed for this evaluation is expensive but echography is undoubtedly less invasive than other equivalent examinations like cavernosography. Although the sensitivity and specificity of penile echography have not yet been clearly established this test is generally considered to be an useful and objective one. Penile echography is particularly usefull in discriminating between echogenic and not-echogenic nodules in case of Peyronie disease. PMID- 1411606 TI - [Ultrasound and color Doppler in the diagnosis of vasculogenic impotence]. AB - Echo-color-doppler is a non invasive diagnostic technique which can provide data about arterial and venous vascular circle of the penis with greater precision than Doppler CW. In the tumescent phase after a PGE1 injection the systolic velocity (SV) reaches a rate higher than 25 cm/sec and the diastolic velocity (DV) higher than 2 cm/sec, resistance index (RI) > to 0.70 with evident colour marked from 1 to 3 KHz. In erection arterial flow decrease and SV is lower than 25 cm/sec with DV lower than 2 cm/sec or with negative values; RI < to 0.70 or negative. The data are confirmed by clinical investigation and traditional diagnostic exams in normal and pathological patients. Echo-color-doppler reduces invasive exams and acquires a primary position on the diagnostic scale of impotence. PMID- 1411607 TI - [Can post-traumatic renal failure be modified therapeutically?]. AB - Acute renal failure in the late phase after severe trauma is particularly dangerous, since it is resistant to therapy and contributes to the development of post-traumatic multiple organ failure. We have studied different treatment regimes in order to establish whether late renal failure can be prevented (study A: colloidal and crystalloid solutions; study B greater than: crystalloid solutions and dopamine; continuous infusion 3 micrograms/kg body weight). Renal function was assessed by means of the score by Goris as well as by creatinine clearance over a period of 14 days. Haemodynamics and cardiac function were determined on a daily basis. The demographic parameters were comparable in both groups. In group A 37 of 61 patients died (60.6%), and in group B 17 of 38 patients (44.7%) (P less than 0.05). The incidence of impairment of renal function was comparable; in group A there was significantly more severe damage (18%) compared to group B (2.6%). This coincided with significantly higher mortality in group A (group A: 60.65%; group B: 44.7%). In group A a lesser volume was given during the preclinical and clinical course, even after correcting for the volume-saving effect of colloidal solutions. In addition, cardiac index was higher in group B (day 9: 5.9 +/- 0.61 l/min) than in group A (day 9: 4.4 +/- 0.5 l/min) and pulmonary capillary wedge pressure (PCWP) was lower and systemic vascular resistance (SVR) higher over the whole period. Also, the arterio-venous oxygen difference (AvDO2) was higher following day 9 in patients in group A, but creatinine clearance was better in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411608 TI - [Differences of acute and chronic epidural hematoma]. AB - Standard neurosurgical management demands prompt evacuation of all extradural hematomas to obtain a low incidence of mortality and morbidity. In selected cases some authors have suggested that moderate hematomas can be managed conservatively without risk to the patient and with a normal outcome. The goal of this study was to analyze the differences in preoperative clinical parameters between a group of acute and a group of chronic extradural hematomas (chronic extradural hematoma was defined as a delay of more than 72 h from the accident to diagnosis). One hundred fifteen (115) patients with extradural hematomas underwent a standard evaluation, documentation and neurosurgical management (prompt evacuation of all extradural hematomas through a craniotomy). Ninety-five patients (83%) had an acute extradural hematoma. Twenty patients (17%) had a chronic extradural hematoma. We analyzed the following parameters: age, cause of accident, clinical findings, Glasgow Coma Score, morphology of hematoma, location of hematoma, cause of bleeding and clinical outcome. The mean age (chronic 30/acute 32) and age distribution were not significantly different between groups. There were no differences in the cause of accident. All patients in both groups had skull fractures. There was no difference between groups regarding hematoma location, most of there being located in the temporal fossa. In the group of acute extradural hematomas, 62% of patients had a Glasgow Coma Score of less than 8 and 47% had pupillary dilation. In the group of chronic extradural hematomas, moderate clinical symptoms were found, with headache and discrete psychological changes most common. Eighty percent (80%) of the patients had a Glasgow Coma Score of greater than 13 and no patients had pupillary dilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411609 TI - [Surgical treatment of fractures in tropical countries]. AB - In tropical countries, the indication for operative treatment of fractures treatment must be restrictive. Based on our own experience and the treatment results, the prerequisites for operative treatment are given and proposals concerning indication, preoperative preparation and operative tactics. The osteosyntheses recommended are the different forms of external fixation, in particular the external fixator (AO) and the transfixational plaster cast technique. The external fixator is the basic tool in tropical traumatology. PMID- 1411610 TI - [Late results after lumbar vertebrae fracture with Lorenz Bohler conservative treatment]. AB - We report on a clinical and radiological follow-up of patients who had sustained a fracture of their lumbar spine between 1982 and 1989 and were treated at our department by the method of Lorenz Bohler. 244 patients left our clinic with a plaster bodice after fracture reposition, 153 came to the follow-up (most of the cases are documented radiologically from the first to the follow-up x-ray). Our results are similar to the outcomes which are published after early functional treatment. We could not find a relationship between the radiological and clinical results and we saw, that it is impossible to fix the spine sufficiently in a plaster bodice without fracture redislocation. PMID- 1411611 TI - [Indications, technique and results of monosegmental dorsal spondylodesis in wedge compression fractures (grade II) of the thoracolumbar spine]. AB - The management of wedge compression fractures of the thoracolumbar spine remains a controversial subject. Although there is an increasing tendency for operative intervention of spinal injuries, non-operative treatment of compression fracture has been the method of choice. The compression fracture is a fracture occurring during compressive forces of the anterior column due to flexion mechanisms. The more severe the compressive fracture, the more likely it will be to present, in an addition to anterior wedging, a failure of the posterior column indicating tension forces at that level. These fractures, defined as mechanically unstable and classified as compression fractures Grade II, are concentrated in the thoracolumbar region. Between June 1987 and July 1990 14 patients with compression fractures Grade II were treated posteriorly with one level internal fixation. Of the 14 patients, 9 had stabilization with plates and cerclage wire, 5 with an internal fixator. All patients received a localized fusion. In order to permit a more reliable analysis of the results of our stabilizing procedures, a comparison was made with a series of 11 cases with equivalent fractures treated non-operatively between 1986 and 1989. At clinical and radiographic follow-up evaluation, the results in the operative group were much more favourable, both subjective and objective, than in the non-operative group. We derive from these results that in thoracolumbar compression fractures Grade II, posterior one level stabilization and fusion is a recommendable surgical procedure. PMID- 1411612 TI - Surgical management of pelvic ring disruptions. Indications, techniques and functional results. AB - In a period of 30 months, we treated 44 pelvic ring fractures by early operative stabilization. The ratio of associated musculoskeletal and intrapelvic lesions was very high, with a mean ISS of 36.2. The perioperative mortality rate (3/44) was acceptable with 6.8%. A second osteosynthesis was performed in fast 8% of type-B and in fast 40% of type-C lesions. The average hospital stay was very short with 42.0 days. We were able to mobilize the patients very early after their admission, thanks to the quick operative stabilization of the pelvic ring and the other skeletal injuries. Of the 39 surviving patients, 35 were reviewed clinically, functionally and radiographically after a mean of 19.3 months. There was a statistically significant difference in the rate of walking difficulties, walking distance, hip mobility, muscle force and the functional end-results between patients with type-B and those with type-C lesions. Lesions of type B are benign and can be adequately treated by the application of an anterior external fixator frame alone. The functional results are excellent or good in the great majority of cases. The type-C lesions are much more difficult to deal with. The anterior external fixator provides insufficient stability in many cases. It must be supplemented by posterior fixation or exchanged for anterior and posterior internal fixation. Even then, many patients with type-C lesions have functional disabilities and subjective complaints after treatment. PMID- 1411613 TI - [Arthroscopic technique for replacing the anterior cruciate ligament using a free patellar tendon transplant]. AB - The replacement of the anterior cruciate ligament (ACL) by a free patellar tendon graft is a well-known procedure. The disadvantage is that the necessary arthrotomy destroys the nerve supply of the joint capsule. Therefore, we developed a procedure of ACL replacement that can be done by arthroscopy without opening the joint except for a small incision needed for the arthroscopy and working canal. The surgical technique is described. PMID- 1411614 TI - Knee-ligament injuries associated with leg fractures. Prospective study. AB - It has been proved in 25-35% of the cases that knee-ligament injuries are associated with fracture of the femoral diaphysis. No such association has been confirmed between leg fractures and knee ligaments. In order to find out if this is a coincidence, a prospective study was conducted on 229 patients who had undergone operations for leg fractures at various locations and of variable intensity. It was established in 41 cases (17.34%) that the leg fracture was associated with knee-ligament injuries, resulting in joint instability. A significantly higher percentage of associated ligament lesions was found in open fractures as opposed to closed leg fractures. The examination was carried out with the patient under general or block anesthesia. On the basis of what was established it is recommended that the knee be examined clinically in all leg osteosynthesis cases. PMID- 1411615 TI - Experience with ifosfamide in the EORTC Soft Tissue and Bone Sarcoma Group. AB - The Soft Tissue and Bone Sarcoma Group of the European Organization on Research and Treatment of Cancer has conducted a number of studies of chemotherapy in advanced disease over the past 15 years. Following the discovery that the CYVADIC regimen (cyclophosphamide/vincristine/doxorubicin/dimethyl imidazole carboxamide) was less active than had been reported originally, the individual components of CYVADIC were studied. This showed that doxorubicin had considerable activity and that ifosfamide 5 g/m2 given over 24 hours was at least as active as cyclophosphamide. Subsequent studies have therefore centered on a combination of doxorubicin and ifosfamide. A large randomized trial showed no significant benefit of doxorubicin/ifosfamide over single-agent doxorubicin, but the doses of doxorubicin were different. More recently, using bone marrow growth factors, it has been possible to increase the doxorubicin dose to that given as a single agent and also maintain the ifosfamide dose. This is now being tested in a randomized trial to determine whether improved response rates and other indicators of outcome will be seen. PMID- 1411616 TI - The clinical management of soft tissue sarcomas. AB - Sarcomas are a relatively rare and heterogeneous group of malignant tumors of principally mesenchymal origin. The histologic grade and size (and possibly compartmental localization) are the main factors predicting local and distant biologic aggressiveness. Tumor localization and surgical margins are significant prognostic factors that relate to the adequacy of local-regional therapy. A general consensus management usually consists of an incisional biopsy for diagnosis and grade, staging of the primary tumor and lungs, and function preserving surgery with margins free of tumor either followed by or preceded by tumor bed high-dose radiotherapy. Each of these concepts remains under active investigation. The role of adjuvant therapy is not yet established despite tantalizing biologic effects documented in their trials. Ifosfamide in addition to doxorubicin does appear to have major activity; however, further laboratory investigation of resistance and metastases mechanisms and new drug evaluations are necessary for further advance. PMID- 1411617 TI - Ifosfamide in pediatric oncology. AB - Ifosfamide is an effective drug for the treatment of solid tumors in children and most blastomas and sarcomas react favorably. It is administered in combination chemotherapy protocols. In young children, nephrotoxicity is a serious side effect. In older boys, gonadal damage is the major late side effect. PMID- 1411618 TI - Combination therapy with carboplatin/cisplatin/ifosfamide/etoposide in ovarian cancer. AB - In 1987 a phase II study of combined high-dose platinum (carboplatin 300/mg/m2 day 1, cisplatin 50 mg/m2 days 2 and 3 q4wk) was carried out in 42 previously untreated ovarian cancer patients with residual disease. Since then, another phase II study of combined high-dose platinum and ifosfamide (1,500 mg/m2 days 1 to 3) has been carried out in 37 patients, while a third study of combined high dose platinum and etoposide (70 mg/m2 intravenously days 1 to 5) is ongoing. Pathologic complete response (CR) and partial response (PR) rates in the first two studies were 62% in 37 evaluable patients, and 58% in 36 patients, 22% and 42% of whom were CRs, respectively. The preliminary results from the third study were: CR plus PR, 56%; CR, 24%. Hematologic toxicity was the dose-limiting factor in all three studies. Myelosuppression became substantial, but manageable, if another drug was added to the platinum combination. The percentage of patients experiencing World Health Organization grades 3 and 4 toxicity during treatment were: white blood cells 44%, 92%, and 79%; platelets 81%, 100%, and 95%, respectively, in studies I, II, and III. Nonhematologic toxicity was modest in all studies. Dose-limiting neurotoxicity occurred in 7%, 6%, and 5%; nephrotoxicity in 22%, 6%, and 11% of the patients. The percentage of patients receiving the stipulated doses of all study drugs in the sixth cycle was 31 in the first study compared with none in the second study. Combined high-dose platinum given either alone or in combination with ifosfamide or etoposide is highly active in ovarian carcinoma. However, further follow-up and a randomized trial are needed to establish the superiority of any one regimen. PMID- 1411619 TI - The role of ifosfamide in gynecologic cancer. AB - Ifosfamide exhibits promising activity in a variety of gynecologic neoplasms. In carcinoma of the ovary, the drug shows clear-cut activity, effecting responses in patients who have proven clinically resistant to cisplatin-based combination chemotherapy. In carcinoma of the cervix, the drug also appears to be highly active, both as a single agent and in combination with other agents, such as the platinum compounds. The drug is active in uterine sarcomas and appears to be the most active agent studied to date in mixed mesodermal sarcomas of the uterus. The drug's role in combination with other agents in the treatment of all of these neoplasms is under study, but cannot be determined from currently available data on combination therapy. Its activity in other gynecologic tumors, such as endometrial carcinoma and ovarian germ cell tumors, is also indeterminate at present. Although further studies are needed, current evidence supports the contention that ifosfamide is a major new active drug in the management of gynecologic cancers. PMID- 1411620 TI - Carboplatin/cyclophosphamide combination chemotherapy for advanced ovarian cancer. AB - The efficacy and toxicity of combination intravenous carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2) were evaluated in 70 newly diagnosed patients with advanced-stage epithelial ovarian cancer. Cycles were administered at 4-week intervals for a total of six cycles, and treatment was provided on an outpatient basis without prehydration or forced diuresis. During treatment, patients were assessed by physical, gynecologic, and radiologic examinations. Seventy patients with a median age of 58 years (range, 35 to 77 years) were entered into the study. Most patients had serious cystadenocarcinoma; 78% had stage III or IV disease and 91% had grade II or III histologic subtype. Optimal debulking surgery was performed in only 46% of patients. The overall response rate to carboplatin/cyclophosphamide combination chemotherapy was 81%, with 66% achieving a clinical complete response. The median survival for all patients was 19+ months. For patients who had undergone optimal debulking surgery, median survival was 26 months, compared with a median survival of 13+ months for those who had undergone suboptimal surgery. Treatment was well tolerated by most patients. Significant nausea and vomiting (World Health Organization grades 2 to 3) occurred in only 6% of 377 cycles of therapy. Myelosuppression was mild, with leukopenia (WBC count less than or equal to 2 x 10(9)/L) observed in only 11 of 295 cycles (4%) and thrombocytopenia (less than or equal to 100 x 10(9)/L) in 17 of 279 cycles (6%). Nadir levels generally occurred on day 21 of each cycle. Symptomatic anemia requiring transfusion occurred in 18 of 290 cycles (6%). Moderate alopecia, necessitating use of a hairpiece, occurred in six patients; no signs or symptoms of neurotoxicity, ototoxicity, or nephrotoxicity were observed in any patient. Renal function was normal on follow-up investigation, which was performed a median of 5 months after completion of treatment. This study demonstrates that carboplatin/cyclophosphamide combination chemotherapy is well tolerated in women with advanced-stage epithelial ovarian cancer, and produces overall response rates and median survival times similar to those obtained with cisplatin-containing regimens. PMID- 1411621 TI - Intraperitoneal carboplatin: rationale and experience. AB - We conducted a phase I/II trial of intraperitoneal (IP) carboplatin in 27 patients with advanced gynecologic malignancies. This was based on the known activity of carboplatin in ovarian cancer and pharmacologic measurements that predict a favorable ratio of IP to plasma drug exposure when carboplatin is administered by the IP route. All patients had extensive prior therapy with cisplatin (mean dose, 554 mg/m2). Starting dose was 200 mg/m2, which was escalated to 500 mg/m2. Patients with compromised renal function (creatinine clearance 30 to 60 mL/min) had slower escalations than patients with creatinine clearances greater than 60 mL/min. Myelosuppression, especially thrombocytopenia, was the dose-limiting toxicity. In pretreated patients, we recommend a starting dose of 400 mg/m2. Patients with creatinine clearances of 30 to 60 mL/min should start at the lower dose of 200 mg/m2. This is in general agreement with the results of other trials of IP carboplatin. Measurements of IP carboplatin in preclinical studies predict less tissue penetration by carboplatin than the parent compound cisplatin. Nevertheless, in our series of heavily pretreated patients receiving IP carboplatin, eight patients remained free of disease progression for more than 2 years. Further trials of IP carboplatin are indicated. PMID- 1411622 TI - Carboplatin in the treatment of carcinoma of the ovary: the National Cancer Institute of Canada experience. Ovarian Cancer Subcommittee. AB - The National Cancer Institute of Canada Clinical Trials Group has used carboplatin in two studies in women with ovarian carcinoma. In a phase II study, carboplatin produced a clinical response rate of 28% among patients with tumor persistence or recurrence following one prior cisplatin-containing regimen. Carboplatin was most efficacious in those with smaller tumors, in those who had the best responses to prior cisplatin therapy, and in those with longer intervals between the primary cisplatin treatment and the secondary carboplatin course. In this setting, a starting dose of 320 mg/m2 is suggested. A phase III randomized trial of first-line therapy compared the efficacy of cyclophosphamide/cisplatin with cyclophosphamide/carboplatin. Four hundred eighteen eligible patients were enrolled. The regimens demonstrated comparable efficacy; however, the carboplatin based regimen was more easily administered and caused less symptomatic toxicity. The long-term results in this population with macroscopic residual disease remain disappointing. PMID- 1411623 TI - Meta-analysis of the role of platinum compounds in advanced ovarian carcinoma. The Advanced Ovarian Cancer Trialists Group. AB - This paper presents a systematic overview or meta-analysis of 54 randomized clinical trials testing a variety of chemotherapeutic approaches in advanced ovarian carcinoma. Prolonged follow-up data are available for most patients and individual patient data were made available for all patients; analysis was made on the basis of "intention to treat." Our report concentrates on two comparisons: (1) platinum alone versus platinum in combination, which appears to show a long term survival advantage for the combination (however, the platinum dose in the single-agent arm was relatively low); and (2) carboplatin versus cisplatin, which shows no obvious survival differences. It is striking that no single study to date has been large enough to detect the modest survival differences expected from current therapy. Consequently, a series of international studies have been initiated. The International Collaborative Ovarian Neoplasm (ICON) group will examine the role of adjuvant chemotherapy in early ovarian cancer (ICON 1) and will compare carboplatin with cisplatin, doxorubicin, and cyclophosphamide in more advanced disease (ICON 2). PMID- 1411624 TI - Utility of individualized carboplatin dosing alone and in combination regimens. AB - Carboplatin represents an ideal candidate for dose optimization in individual patients. The excellent correlations between renal function and carboplatin total body clearance and between carboplatin area under the plasma concentration by time curve (AUC) and thrombocytopenia allow calculation of carboplatin dosages that simultaneously minimize the likelihood of toxicity and maximize the amount of drug that can be delivered. Current studies are defining the essential relationship between carboplatin AUC and the likelihood of achieving a therapeutic response in various tumor types. These quantitative relationships between carboplatin AUC and thrombocytopenia and AUC and response should be the foundation for the intelligent use of carboplatin as an individual agent and for the intelligent assessment of the beneficial or adverse effects of other agents when combined with carboplatin. PMID- 1411626 TI - Current experience with high-dose carboplatin therapy. AB - Carboplatin is well suited to dose escalation because its major dose-limiting toxicity is myelosuppression when given in 1,200 mg/m2 doses without marrow support. Repeated 800 mg/m2 doses can be given in an investigational setting. With autologous bone marrow rescue the maximum tolerated single-agent dose is approximately 1.8 to 2 g/m2, with dose-limiting toxicities being hepatitis, renal dysfunction, and ototoxicity. Combinations of carboplatin with other agents plus bone marrow rescue are now being investigated in germ cell tumors, ovarian cancer, breast cancer, and small cell lung cancer. High-dose carboplatin plus etoposide combinations are being evaluated with colony-plus stimulating factors in an effort to ameliorate myelosuppression. Future high-dose carboplatin studies could be designed with more predictable toxicity, using an assessment of carboplatin renal clearance. Carboplatin is an important new drug warranting further investigation at escalated doses. PMID- 1411625 TI - A dose-escalation study of carboplatin/cyclophosphamide/etoposide along with autologous bone marrow or peripheral blood stem cell rescue. AB - Twenty patients have received 21 courses of high-dose cyclophosphamide (6 g/m2 over 4 days), etoposide (1,800 mg/m2 over 3 days), and carboplatin (800 to 1,600 mg/m2 by continuous infusion over 96 hours) and autologous bone marrow or peripheral blood stem cell rescue. The maximum tolerated dose of this regimen included these doses of cyclophosphamide and etoposide with a total of 1,600 mg/m2 carboplatin. Acute renal failure was the dose-limiting toxicity and, at the maximum tolerated dose, was observed in two patients of 14 evaluable courses. Nonhematologic toxicity was otherwise modest, and the overall response rate was 70% in patients with a wide variety of solid hematologic neoplasms. PMID- 1411627 TI - Future directions with carboplatin: can therapeutic monitoring, high-dose administration, and hematologic support with growth factors expand the spectrum compared with cisplatin? AB - This paper reviews the role of pharmacokinetic methods in the clinical use of carboplatin. Published data establish that pretreatment renal function is the most significant determinant of carboplatin pharmacokinetics. Evidence suggests that the area under the plasma concentration versus time curve (AUC) correlates well with hematologic toxicity. Published data also suggest that a relationship exists between the AUC and therapeutic outcome in testicular teratoma and in ovarian cancer, although in the latter case the data are not conclusive. It is suggested that pharmacokinetically based dosing schemes may be advantageous and that randomized trials should be performed to test this hypothesis. In some clinical situations where dose prediction is not feasible, a simple therapeutic drug-monitoring strategy may prove useful. Since the toxicities of carboplatin are mainly hematologic, it has been possible to study the use of high-dose carboplatin with various forms of hematologic support. Carboplatin doses have been increased fourfold to sixfold and high response rates have been reported in ovarian cancer. An overall therapeutic advantage for this strategy has not yet been demonstrated in a randomized setting. Published data on ovarian cancer cell lines suggest that the range of sensitivities encountered is very large (30- to 100-fold). If the range of sensitivities found in vivo is equally large, then a clinical dose escalation of 10- to 100-fold may be necessary to produce a curative therapy for this disease. The investigation of the use of hematopoietic growth factors in association with carboplatin has just begun. Early data suggest that some support of the WBC count may be achieved, but the toxicities of granulocyte-macrophage colony-stimulating factor have themselves been a problem. Our own studies will attempt to achieve a substantial escalation in the administered AUC of carboplatin by increasing the frequency of carboplatin dosing, while administering granulocyte colony-stimulating factor and platelet support. PMID- 1411628 TI - Carboplatin in the treatment of squamous cell head and neck cancers. AB - Cancer of the head and neck, or aerodigestive tract, represents only a small percentage of all cancer cases in the United States, yet its variable presentations have wide-ranging implications that make it one of the most problematic cancers. Recent research has focused on treatment approaches for the patient with advanced disease. Encouraging results have been noted with combination cisplatin/5-fluorouracil (5-FU) and, more recently, with carboplatin/5-FU, particularly in previously untreated patients. The carboplatin containing regimen has several important advantages over that with cisplatin, including outpatient administration and less severe nausea and vomiting, an important consideration in terms of nutritional support for head and neck cancer patients. The demonstration of possible synergistic activity between platinum compounds and radiation therapy also has prompted considerable interest, as such a combined-modality approach offers the potential for improved quality of life in patients with head and neck cancers. Carboplatin is an excellent agent for the treatment of squamous cell head and neck cancers, with recognized single-agent activity and a high degree of efficacy, when combined with 5-FU. Carboplatin can be combined effectively with concurrent radiotherapy and, with its advantages over cisplatin, is increasingly used as part of initial therapy for head and neck cancers. PMID- 1411629 TI - Phase I/II study of simultaneous carboplatin and radiotherapy in unresectable squamous cell carcinoma of the head and neck. AB - Escalating dose levels of carboplatin together with simultaneous accelerated radiation were administered to 36 previously untreated patients with unresectable carcinomas of the head and neck (two stage III and 34 stage IV disease). Twenty three patients received a total radiation dose of 58.8 Gy with two daily fractions of 2.1 Gy on days 1 to 4 in weeks 1, 2, and 5 and on another 2 days in week 6. Simultaneous carboplatin was given intravenously in escalating dose levels: 20 mg/m2 in three patients, 30 mg/m2 in five patients, 40 mg/m2 in five patients, 50 mg/m2 in six patients, and 60 mg/m2 in four patients. Another 13 patients were treated with an escalated radiation dose of 67.2 Gy, which led to 2 additional days of chemoradiotherapy in week 6. Six patients in this group received carboplatin 60 mg/m2/d, and seven received 50 mg/m2/d. All patients were evaluable for toxicity according to World Health Organization (WHO) criteria, and 35 of 36 patients were evaluable for response. Dose-limiting toxicity was myelosuppression, with WHO grades 3 and 4 leukopenia in five of six patients treated with carboplatin 60 mg/m2 and 67.2 Gy radiation. In patients treated with carboplatin 50 mg/m2 and 67.2 Gy radiation, no grade 4 myelosuppression developed and toxicity was generally tolerable. Independent of the carboplatin dose, grade 3 or 4 mucositis was seen in 12 patients. No other toxicities above grade 2 occurred. There were 19 complete responses (53%) and 16 partial responses (44%). Comparing these results with our earlier data with sequential chemoradiotherapy (carboplatin/5-fluorouracil followed by conventional radiotherapy) indicated that the higher tumor-clearing rate of simultaneous chemoradiotherapy produced significantly better rates of survival and disease-free response. PMID- 1411630 TI - Cisplatin and platinum analogues in breast cancer. AB - Therapy for metastatic breast cancer can palliate disease and prolong life, but cannot cure. New drugs will be required if this is to change. Cisplatin and its analogue carboplatin offer new approaches to the treatment of metastatic breast cancer. Cisplatin has significant single-agent, front-line activity in metastatic breast cancer. In combination with other agents (eg, etoposide or 5 fluorouracil), it provides response rates equivalent to other front-line combinations. The activity of carboplatin as a single agent is reportedly less than that of cisplatin in single-agent trials, and few combination trials have been reported. Both cisplatin and carboplatin, when used in high doses in the setting of autologous bone marrow transplantation, appear to be useful agents for the treatment of metastatic disease. Further research is needed to define the role of these compounds in the treatment of breast cancer. PMID- 1411631 TI - New developments with carboplatin in the treatment of ovarian cancer. AB - On the basis of prospective randomized comparisons, carboplatin now can be considered to have replaced cisplatin as the induction chemotherapy of choice for patients with advanced ovarian cancer. While its equal efficacy and lesser toxicity are encouraging features of carboplatin therapy, the primary goal of chemotherapy for ovarian cancer remains to improve cure rates. It is in this regard that new experimental studies with carboplatin have the potential for improving survival. In particular, studies of dose intensity of platinum compounds are now possible with high-dose carboplatin together with autologous bone marrow transplantation and cytokines. The dose-limiting toxicity of carboplatin is myelosuppression, particularly thrombocytopenia. It is hoped that the new cytokine, interleukin-3, will be useful in reversing this particular toxicity and permitting further dose escalation. Additional studies are in progress to evaluate the benefits of combining carboplatin and cisplatin in an effort to maximize dose intensity and avoid overlapping toxicities. PMID- 1411632 TI - Role of carboplatin in endometrial and cervical carcinomas. AB - The role of carboplatin in cervical and endometrial cancers is being assessed through clinical trials. Preliminary results indicate some activity against both of these gynecologic tumors. Carboplatin is also being integrated into combination regimens with other active drugs. In the treatment of cervical cancer, it is used as part of combined-modality regimens prior to radiotherapy. Patients have shown better subjective tolerance to carboplatin than to cisplatin. This finding may facilitate the widespread implementation of carboplatin-based combinations. PMID- 1411633 TI - Neoadjuvant therapy for cervical cancer. AB - The stage-by-stage prognosis for cervical cancer patients has not improved in the past decades. Our research work concerning adjuvant chemotherapy for the early stages induced a pilot study with untreated patients in advanced stages. Patients were treated with carboplatin 300 mg/m2 plus ifosfamide 5 g/m2 on day 1. In cases of remission or no change, the therapy was repeated after 4 weeks. A third course was given only after further remission. After chemotherapy, patients were treated with surgery or radiotherapy according to feasibility. A total of 34 patients were admitted to this study. Thirty-two patients with 88 chemotherapy courses were evaluable for response and toxicity. Nineteen patients achieved remission; three achieved complete remission. The most common toxic effects were myelosuppression with grade four leukopenia (28%) and thrombocytopenia (13%). Alopecia (60%) was the main nonhematologic toxicity. In conclusion, we suggest that this regimen is as effective as other platin-containing regimens for squamous cell carcinoma of the cervix uteri, but its hematologic toxicity precludes its recommendation in an adjuvant setting. PMID- 1411635 TI - Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives. AB - Etoposide and teniposide are closely related derivatives of podophyllotoxin, and both have a phase-specific action in the late S and early G2 phases of the cell cycle. Etoposide has attracted more widespread use and study, although no evidence suggests a differing mode of action or spectrum of anticancer activity. The drugs have significant differences in their clinical pharmacology, however. Teniposide exhibits greater protein-binding affinity, has a longer plasma terminal elimination half-life, and has reduced plasma and renal clearances. Little is accurately known about the metabolism of either drug, but the fact that 40% to 60% of administered etoposide is accounted for by excretion or metabolism, whereas the range is only 10% to 25% for teniposide, reflects a further difference between the drugs. Renal dysfunction impairs etoposide excretion, but the effect of hepatic impairment on drug clearance is unclear. A specific oral formulation exists only for etoposide, although the unpalatable intravenous preparations of both drugs can be taken orally. The bioavailability of oral etoposide is about 50% at doses of 200 mg or less and decreases as drug doses increase. There is considerable intrapatient and interpatient variation in etoposide absorption, but the reasons for this are unknown. In vitro, the efficacy of etoposide is highly dependent on the schedule of administration. The superior efficacy without increased toxicity of more prolonged schedules of etoposide administration has been demonstrated recently in patients with small cell lung cancer (SCLC). Although the optimal schedule in any specific tumor is not known, current pharmacodynamic evidence suggests that the efficacy of etoposide, at least in SCLC, is related to the maintenance of prolonged low blood concentrations of drug. PMID- 1411634 TI - Replacement of cisplatin with carboplatin in combination chemotherapy against ovarian cancer: long-term treatment results of a study of the Gynaecological Cancer Cooperative Group of the EORTC and experience at The Netherlands Cancer Institute. AB - Carboplatin-based chemotherapy has been evaluated in three studies of ovarian cancer patients. In the first, combination cisplatin and carboplatin plus doxorubicin/hexamethylmelamine/cyclophosphamide were compared as first-line treatment of ovarian cancer in 341 women with stage IIB to IV disease. There were no observed differences in results between the two treatment groups. In the second study, conventional doses of intravenous carboplatin (350 mg/m2, given on day 1) plus oral cyclophosphamide (100 mg/m2 days 2 to 6) were given to late relapsing patients (12 to 72 months) previously treated with cisplatin. Mature data showed a 55% overall response rate, acceptable toxicity, and an absence of additive neurotoxicity. Finally, 65 patients with refractory disease or in early relapse after cisplatin therapy (within 12 months) were treated with high-dose carboplatin (800 mg/m2). Toxicity was severe, but the 45% combined response rate was considered encouraging and worthy of further evaluation. It was concluded that carboplatin is an appropriate replacement for cisplatin in the treatment of ovarian cancer. PMID- 1411636 TI - Absolute bioavailability and pharmacokinetics of oral teniposide. AB - The absolute bioavailability and pharmacokinetics of orally administered teniposide were investigated in 25 patients. All patients received 50 to 60 mg/m2 teniposide intravenously on day 1, before oral administration. Six patients received 60 mg/m2 as a single oral dose on day 8; 5 patients received 60 mg/m2 and 120 mg/m2 as a single oral dose on days 8 and 15, respectively; 5 patients received 120 mg/m2 and 240 mg/m2 as a single oral dose on days 8 and 15, respectively; 6 patients received 60 mg/m2 as a single oral dose on 5 consecutive days from days 8 to 12; and 3 patients received 50 mg/m2 three times a day at 6 hour intervals on day 8. The mean absolute bioavailability was 41.6% +/- 14.2% with a large interindividual variability (range, 19.7% to 71.4%) and a low intraindividual variability (range, 2.8% to 13.9%). At a dose of 240 mg/m2, the bioavailability was decreased, whereas administration of multiple doses on 1 day or 5 consecutive days increased the overall bioavailability. In conclusion, teniposide can be administered orally with a bioavailability comparable with that of etoposide. The schedule dependency of both drugs warrants investigations of oral administration for 21 or more days. A formulation of teniposide capsules of 50 mg or less would be most helpful to facilitate oral administration. PMID- 1411637 TI - A phase I study of daily oral teniposide for 20 days. AB - In this phase I study, teniposide was administered orally for 20 consecutive days to patients with refractory cancers. All patients but one were pretreated. When given for 20 consecutive days, the maximum tolerated dose of teniposide was 100 mg/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 17 and 31. In all patients blood counts had sufficiently recovered by day 35 to begin another 20-day course. Gastrointestinal toxicity persisted in 6 of 15 patients despite antiemetics. Total alopecia was observed in 10 of 13 patients at risk. We recommend teniposide 100 mg/d for 20 consecutive days for evaluation of antitumor efficacy in phase II studies. PMID- 1411638 TI - Teniposide in adult solid tumors: a historical perspective. AB - Teniposide and etoposide are third-generation semi-synthetic derivatives of epipodophyllotoxin. Following the initial clinical introduction of teniposide in the 1970s, investigations focused almost exclusively on its analogue, etoposide, because of its formulation, which was felt to have advantages in addition to oral administration. Despite consistently inadequate dosing and scheduling, early phase I and II trial results with teniposide were promising, and current trends encourage a second look. The substantial antitumor activity of teniposide is comparable with that of etoposide, and clinical interest was rekindled when it was shown to have considerable activity against small cell lung cancer (SCLC). In view of the inadequacy of early trials and the premature cessation of clinical study, it is recommended that teniposide be reevaluated for its activity against malignant lymphomas, Hodgkin's disease, leukemias, and SCLC, against all of which its early results were encouraging. In addition, consideration should be given to its activity against brain tumors, neuroblastomas and other childhood solid tumors, and ovarian cancer; its potential value against gastric, hepatocellular, breast, and bladder cancers also should be investigated. Other areas that warrant further study include elucidation of the exact mechanism of action of teniposide, its role in both single- and multiple-agent chemotherapeutic regimens, and resolution of its optimal dose and schedule. Finally, it is suggested that with new routes of administration and improved formulations, teniposide may be expected to play a significant role in the treatment of malignant lymphomas, SCLC, and pediatric lymphocytic leukemia and neuroblastoma. PMID- 1411640 TI - Teniposide in lymphomas and leukemias. AB - The epipodophyllotoxins, etoposide and teniposide, have been used in leukemias and malignant lymphomas for the past 15 years. Although etoposide has acquired a place in many first-line protocols for lymphomas and, more recently, for leukemias, the role of teniposide has remained limited. Teniposide is a more potent inhibitor of topoisomerase II than etoposide, and has a less toxic effect on hematopoietic progenitor cells. Both drugs have been regarded as equitoxic and cross-resistant. The role of teniposide in front-line treatment of leukemias has only been established in childhood acute lymphoblastic leukemia (ALL). Some promising results have been obtained in small numbers of patients with refractory adult ALL and acute monoblastic leukemia. However, the remission rates and remission duration were not significantly different from those of other combination regimens. Data on teniposide in untreated acute nonlymphoblastic leukemia are very scarce. In non-Hodgkin's lymphoma, the antineoplastic activity of teniposide has been demonstrated in studies by the European Organization for Research and Treatment of Cancer and in two large studies conducted by the Australian and New Zealand Lymphoma Co-operative Chemotherapy Study Group. In these studies, teniposide had comparable but not significantly better activity than vincristine. The dose-dependent antineoplastic activity of teniposide has led to its use in several conditioning regimens in bone marrow transplantation for leukemias and lymphomas. The limited clinical data currently available on teniposide seem to warrant further clinical trials with this agent in leukemias and lymphomas. PMID- 1411639 TI - Clinical trials of teniposide (VM-26) in childhood acute lymphocytic leukemia. AB - We describe the development of VM-26 (teniposide) as an effective agent in combination chemotherapy for childhood acute lymphocytic leukemia (ALL). Beginning with its paired use with cytarabine for patients relapsing on conventional therapy, teniposide has shown consistent ability to reduce leukemic cell populations not responsive to other agents. Encouraging results in the treatment of refractory ALL led to the decision to incorporate teniposide into combination chemotherapy for patients with newly diagnosed leukemia. This strategy has yielded higher cure rates for subsets of patients at high risk of treatment failure, including those with initial leukocyte counts of more than 100 x 10(9)/L, and may extend remission lengths for all patients, regardless of risk status. In view of the prolonged marrow aplasia seen with use of teniposide and cytarabine as inducing agents, the optimal role of this combination may be that of "remission reinforcement" therapy. Because of its novel mechanism of action, teniposide affords opportunities to develop new drug combinations that may increase the proportion of long-term ALL survivors still further. PMID- 1411641 TI - The role of epipodophyllotoxin derivatives in bladder cancer. AB - Past and present experiences with podophyllin derivatives in bladder cancer are described. A preliminary study of teniposide was conducted in 1975 at the Institute of Urology, University of Palermo, in patients with advanced or superficial bladder cancer. In 18 patients with advanced bladder cancer, teniposide was administered intravenously (IV), followed in seven patients by peptichemio or doxorubicin. One complete response (CR) and four partial responses (PRs) were achieved. In 24 patients with superficial tumors, teniposide at a dose of 50 mg dissolved in 30 mL normal saline was administered intravesically as ablative therapy or as prophylaxis following transurethral resection (TUR). Of 12 patients in the ablative therapy group, two CRs and two PRs were achieved. Only 2 patients of 12 in the prophylaxis group relapsed within 6 months. In five cases, teniposide was administered in combination with peptichemio. In recent years, the Urological Group of the European Organization for the Research and Treatment of Cancer (EORTC) has performed a phase II study in which teniposide was used in combination with cisplatin given IV in the treatment of advanced bladder cancer. The EORTC group has also performed a randomized study to compare intravesical teniposide versus thiotepa versus no treatment other than initial resection. A brief report on both studies is given. In December 1987, a study was initiated to evaluate intravesical etoposide use in the prophylaxis of recurrences of superficial transitional cell carcinoma of the bladder. Intravesical etoposide (200 mg dissolved in 50 mL saline solution) was administered at weekly intervals for the first month after TUR and then monthly for 11 months. Of 38 evaluable patients, 20 had recurrences at a mean follow-up of 14 months. No systemic toxicity was noted. PMID- 1411642 TI - Teniposide (VM-26) in brain tumors. AB - Although teniposide activity in glioma was reported as early as 1971, it is only within the last 2 to 3 years that its effectiveness in small cell lung cancer and, most dramatically, in associated brain metastasis, has undergone long overdue systematic investigation. The drug appears to enjoy preferential uptake by brain-tumor tissue compared with disease-free brain tissue. Single-agent activity of teniposide in astrocytomas has been widely reported but the data are difficult to interpret due to differences among studies in definition of response and response duration. Combination therapy has focused primarily on teniposide with nitrosoureas and, again, definition variations have made it difficult to evaluate data. Similar problems plague trials by one group of investigators who reported that the combination of teniposide with doxorubicin and lomustine resulted in regression or improvement in significant percentages of their patients. While many studies indicate that teniposide has significant potential in treatment of adult glioma, controlled trials are needed to evaluate and optimize the use of this agent. PMID- 1411643 TI - Teniposide (VM-26) in ovarian cancer: a review. AB - Relatively few patients with gynecologic malignancies have been included in trials with teniposide given as a single agent. For 109 patients with advanced ovarian cancer treated with various doses and schedules, an overall response rate of 12% was reported. Most patients were heavily pretreated and presumably had resistant disease. Information about teniposide's activity in combination with other cytotoxic agents, as well as its efficacy in other gynecologic malignancies, is limited. In view of the favorable pharmacologic and toxicity profiles of teniposide and its possible synergism with cisplatin and carboplatin, new treatment strategies are discussed that may have implications for further investigation of the usefulness of teniposide in advanced ovarian cancer. PMID- 1411644 TI - Toxicology of chemotherapy. PMID- 1411645 TI - Toxicity: ten years later. PMID- 1411646 TI - Oral toxicity of chemotherapeutic agents. PMID- 1411647 TI - Ocular toxicities of chemotherapy. PMID- 1411648 TI - Dermatologic toxicity of chemotherapy. PMID- 1411649 TI - Pulmonary toxicity of antineoplastic therapy. AB - Pulmonary toxicity is often encountered in patients receiving antineoplastic therapy. It may produce a wide variety of clinicopathologic syndromes. As new agents are introduced and their adverse effects recognized, clinicians should be ever vigilant about the possibility of pulmonary toxicity. PMID- 1411650 TI - Renal toxicities of chemotherapy. PMID- 1411652 TI - Hematologic effects of chemotherapy. PMID- 1411651 TI - The cardiotoxicity of chemotherapeutic drugs. PMID- 1411653 TI - Chemotherapeutic agents and hepatotoxicity. PMID- 1411654 TI - Gastrointestinal toxicity of chemotherapeutic agents. PMID- 1411655 TI - Vascular toxicity associated with antineoplastic agents. AB - It is apparent that a variety of vascular disorders have been reported after the administration of antineoplastic agents. However, it is not clear whether all of these entities are related to cytotoxic drugs, the malignancy itself, or some other unrelated factor. Nonetheless, there does appear to be a cause-effect relationship between cisplatin, bleomycin, velban chemotherapy, and Raynaud's phenomenon. In addition, painful acral erythema may occur in association with several drugs, especially protracted infusions of 5-fluorouracil and high-dose cytosine arabinoside. Mitomycin is the most common cause of the thrombotic microangiopathic syndrome, and in the majority of cases it is a lethal event. Unfortunately, HVOD is a major toxic effect of many preparatory bone marrow transplantation protocols and ways to prevent this potentially life-threatening complication should be avidly pursued. In this regard, pentoxifylline and low dose heparin have recently been reported to be effective in preventing HVOD. Although recent reports have documented thromboses and thromboembolic events in patients with breast cancer treated with cytoxan, methotrexate, and 5 fluorouracil-based protocols, only one study had a no-treatment control arm. Future breast cancer studies should evaluate this problem prospectively. More studies are needed to help elucidate the pathogenesis of vascular toxicity associated with chemotherapy. PMID- 1411657 TI - Breech presentation and delivery. PMID- 1411656 TI - Prospects for fertility after cancer chemotherapy. PMID- 1411658 TI - Health is wealth. PMID- 1411659 TI - Neonatal outcome of breech babies in Toa Payoh Hospital 1984-1989. AB - From 1984 to 1989, a total of 575 breech babies were born out of 21,243 livebirths (2.71%) in the Toa Payoh Hospital, Singapore. There were 259 male and 316 female infants, a sex ratio of 1 to 1.22. There were also no marked differences in the frequency of breech birth among the different racial groups. Many breech babies (385 or 67%) were delivered by Caesarean section and the mortality and morbidity were noted to be low in this series. We had 7 deaths, all weighing below 2000gm and only one, a premature infant, was delivered by Caesarean section. The majority of the infants had no evidence of asphyxia at birth (87.7%); and for those who had asphyxia (13.3%), two-thirds were delivered vaginally and one-third, by Caesarean section. The malformation rate in breech babies was twice that of non-breech babies (7.13% vs 3.08%, p = 10(-6)). Most birth defects were minor in nature. Only 10% of birth defects were major malformations. 5.9% (34) of all the breech babies were low birth weight (LBW), 1/3 (11) of them were delivered by Caesarean section with one death. However, there was no increasing trend of Caesarean section for LBW breech infants in the Hospital. Over the past 6 years, out of the 23 LBW breech babies delivered vaginally, 6 deaths were noted. There were 13 breech stillbirths, the majority of which were macerated (7/13 or 53.8%). The stillbirth rate (SBR) for breech was 22 per 1000 breech livebirths and stillbirths. The SBR for babies born normally was 5.15. The corrected breech SBR was 18.7 after exclusion of lethal malformations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411660 TI - Health promotion--a further field to conquer. AB - We examine some of the interpretations of health promotion. A brief review of the effectiveness of some health promotion programmes in the community and at the worksite in the United States is also presented in view of the similarity of its disease pattern with Singapore. We recommend the following strategies for the practice of health promotion in Singapore: formulation of clearly defined goals; intersectoral collaboration and community participation. Tanahill's model based on the overlapping spheres of health education, disease prevention and health protection is useful in identifying key groups and their roles in health promotion. Green's PROCEED-PRECEDE planning framework which identifies the various behavioural and environmental factors affecting health can help in deriving a highly focused subset of factors as targets for intervention. Research in health promotion should focus on compliance studies on healthy lifestyle regimens, and qualitative and quantitative evaluative studies on process and outcomes of different interventions. PMID- 1411661 TI - 1992 SMA Lecture. The doctor's role in a high-tech world. PMID- 1411662 TI - Surgery for brain metastases in Singapore. AB - The best possible treatment for a single metastasis to the brain is complete surgical excision followed by whole brain irradiation. A survey was done to determine the proportion of patients with brain metastases who had surgical excision of the lesion. The number of patients with a preoperative diagnosis of cerebral metastases who underwent surgical excision in Tan Tock Seng Hospital from 1985 to 1989 was obtained from the operation records. An average of 11 surgical excisions were done for cerebral metastases annually. To estimate the number of cases of single brain metastases seen annually in Singapore, figures of cases of cancer of the lungs, breast and colorectum from 1978 to 1982 were obtained from the Singapore Cancer Registry. Based on a conservative estimate that 20% of these cancers metastasize to the brain, that 50% are single metastasis and of these, half are suitable surgical candidates, our calculations show that there are at least 67 cases of surgically excisable single brain metastasis in Singapore annually. This means that more than 84% of patients with a single brain metastasis are not getting the best possible treatment. The reasons may be due to patients' fear of operation and to lack of awareness among physicians on advances in the management of brain metastases. Patient education and physician update on recent advances in treatment will allow patients to obtain the best possible treatment. PMID- 1411663 TI - Surgical treatment of metastatic long bone disease. AB - A retrospective study of the results of operative treatment of 60 long bones secondaries in 46 patients was carried out. The mean period of follow-up was 10 months. The most common primary in this study was carcinoma of the breast (28.2%), followed by carcinoma of the lung (21.7%) and unknown primary (10.9%). Three groups of patients were studied--pathological fracture group, prophylactic fixation group and a mixed group. In the pathological fracture group, 70% of patients achieved good to excellent pain relief and 60.9% was able to walk with or without walking aids. In the prophylactic group, all the patients achieved good to excellent pain relief and 60% were able to ambulate with or without walking aids. In the mixed group, all the patients achieved good to excellent pain relief and 66.6% of the patients were able to walk with aids. The operative mortality in both the pathological fracture group and prophylactic fixation group was 10% and 33.3% in the mixed group. Multiple internal fixation performed at one operative session was associated with high operative mortality (50%). PMID- 1411664 TI - Urinary tract infection in acute spinal cord injury. AB - Preservation of renal function and prevention of recurrent urinary tract infections is the ultimate goal of any method of neurogenic bladder management in spinal cord injury patients. METHOD--The hospital courses of fifty such patients admitted to our Rehabilitation Department from August 1989 to August 1990 were studied according to age, gender, spinal cord injury level, method of bladder drainage on admission and upon discharge, type of urinary tract infections and results of bladder management were documented. RESULTS--Forty-five men and ten women were studied. Mean age of males was forty and females, forty-two. The commonest cause of injury was road traffic accident followed by accidents at work place. Fifty-three percent had cervical cord injuries, thirteen percent thoracolumbar and sixteen percent lumbo sacral injuries. Seventy-eight percent had an indwelling foley catheter upon admission. Upon discharge eighty-two percent of spinal cord injury patients were able to void with/without tapping and compression. There were a total of one hundred and forty-three urinary tract infections in our study group. All positive urine cultures had greater than or equal to 100,000 CFU/ml. The commonest organisms causing urinary tract infection were Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Proteus mirabilis. CONCLUSION--For bacteria to produce disease in the urinary tract, they must gain access and colonise the uroepithelium, induce inflammation and tissue damage. The indwelling catheter provides a direct access to the uroepithelium, making bacteriuria and subsequent infection inevitable. Impaired voiding and sensation in spinal cord injury patients provides an excellent reservoir for the multiplication of bacteria, tissue invasion and recurrent urinary tract infection. Hence current methods of neurogenic bladder management have to focus on attaining a catheter-free status as soon as possible; relevant antibiotic therapy and careful attention to individual urinary tract problems to reduce morbidity and improve on spinal cord injury patient's future. Although spinal cord injury patients are described, the material covered is applicable to any type of neurogenic bladder dysfunction. PMID- 1411665 TI - Difficult intubation: a prospective study. AB - Difficult intubation has been much discussed in the anaesthetic literature. The incidence of difficult intubation (11:560) was higher in obstetric patients (6:277) as compared to gynaecological patients (5:283) in our hospital. We tested the Mallampati's classification as a predictor of difficult intubation in 277 obstetric and 283 gynaecological patients. We recommend that Mallampati's classification can be used reliably (p less than 0.05) to predict difficult intubation in obstetric but not in gynaecological patients. PMID- 1411666 TI - Sero-prevalence of hepatitis B infection among dental professionals. AB - Dental employees in government institutions in a State in Peninsular Malaysia were screened for exposure to hepatitis B virus (HBV) in 1989. Almost all (96.8%) of the 217 employees responded. One quarter (24.8%) was positive for at least one serological markers to HBV; 2.4% had hepatitis B surface antigen (HBsAg) and 22.4% had anti-body to HBsAg (anti-HBs). The presence of HBsAg was unrelated to age, sex, ethnicity, geographical locality and occupations of the subjects. The prevalence of anti-HBs increased with age and was highest for ethnic Chinese (53.6%), followed by Indians (25%), compared to Malays (14.9%) (p less than 0.001) and were increased among dentists (53.1%) and assistant nurses (33.3%). The overall prevalence of HBsAg and anti-HBs were similar to the situation in the community. However, dentists and their chairside assistant nurses, with a higher proportion of Chinese, had higher anti-HBs prevalences compared with that of the general population. PMID- 1411667 TI - Single-dose and steady-state effects of controlled-release salbutamol on drug level and airflow obstruction in patients with asthma. AB - Oral medication remains the mainstay of treatment for many asthmatics. We compared the single dose and steady-state effects of twice daily 4 mg and 8 mg controlled-release salbutamol (CRS) on plasma salbutamol and FEV1 in 10 asthmatic patients in a double-blind, double-dummy, cross-over study. On 5 separate days, one week apart, we measured FEV1 and plasma salbutamol hourly for 12 hours after a single dose and, after twice daily doses (4 mg, 8 mg or placebo CRS) for one week. Controlled-release salbutamol showed controlled release properties and dose effect for the two doses. At steady-state, it provided relatively constant plasma levels for 12 hours. Significant and similar bronchodilatation occurred after both 4 mg and 8 mg CRS taken either as a single dose or a steady-state regime. PMID- 1411668 TI - Comparison of two assays for the detection of haemolysins of Aeromonas species. AB - The haemolysins produced by Aeromonas species were detected and compared by two assay methods--a modified blood agar plate assay and the rabbit erythrocyte haemolysin method. Both assays showed a high level of agreement (86%). The titres of the rabbit erythrocyte haemolysin assay correlated with the haemolytic zone diameter of the ox blood agar assay. In addition the agar haemolysin assay had simple media requirements, was easy to perform and results were well defined. PMID- 1411669 TI - Wide versus selective decompression in the operative treatment of lumbar spinal stenosis. AB - The early post-operative results of wide versus selective decompression in a group of 64 patients with lumbar spinal stenosis were studied with the aim of ascertaining whether a more limited approach gives comparable results to the more traditional method of wide decompression. Wide decompression involved complete removal of a vertebral lamina at the stenotic level. Selective decompression refers to removal of the lower part of the superior lamina and the upper part of the inferior lamina at the stenotic level together with limited facetectomies. Patients were compared with respect to post-operative relief of back pain and sciatica/claudication as well as the ability to return to their pre-morbid level of functional activity. Follow up ranged from 4 months to 26 months. Results showed that both wide and selective decompression were able to achieve complete or considerable relief of symptoms and return to pre-morbid level of activity in 74% to 84% of patients. The results in the 2 groups were not statistically different. It appears that within the first 2 years of surgery, the vast majority of our post-decompression patients had good results regardless of whether wide or selective decompression was used. PMID- 1411670 TI - Kielland's forceps delivery: is it a dying art? AB - A retrospective study in the use of Kielland's Forceps for rotation of the foetal head and mid-cavity delivery in Kandang Kerbau Hospital, Singapore from 1987-1990 is presented. Out of a total of 53,889 singleton births during this period, Kielland's Forceps was used for delivery in 137 (0.25%) patients with an incidence of 0.65% in the primiparae and 0.07% in the multiparae. Primiparity, induction of labour and epidural analgesia were associated with a significantly higher incidence of rotational delivery by Kielland's forceps. The success rate of Kielland's forceps delivery was 93.4% (128 of 137). There was no maternal or perinatal mortality. About one-third of the mothers experienced postpartum morbidity, commonest being retention of urine, postpartum haemorrhage and vaginal lacerations. Traumatic injuries were present in about one-quarter of the babies and were minor. Out of a total of 306 mid-cavity deliveries for occipito transverse malposition, Kielland's forceps accounted for 38.2% (117), vacuum extraction 30.7% (94), manual rotation followed by Neville-Barnes forceps 11.1% (34) and Caesarean section 20.0% (61). The junior specialists tended to use vacuum extraction for rotational delivery more than the senior specialists. PMID- 1411671 TI - The mental diseases hospital, Singapore (the first 100 years)--a short history (Part I). AB - This article (in four parts) traces the history of the first four Mental Hospitals built in Singapore, which were occupied in 1840, 1861, 1887 and 1928. The management of the patients is described; also their lives and deaths. Mention is also made of the doctors and others who looked after them. PMID- 1411672 TI - Gout. AB - Gout is a common disease in the primary health care setting. Diagnosis of primary gout is definite if urate crystals are present in synovial fluid or tophi. The colchicine therapeutic trial is a useful diagnostic aid but not specific. Secondary gout is associated with myeloproliferative disease. Non-steroidal anti inflammatory agents or colchicine are the main stays of treatment in acute gouty arthritis. In the inter-critical period, uricosuric agents or allopurinol can be used to control hyperuricaemia. Allopurinol is the treatment of choice in secondary gout. Asymptomatic hyperuricaemia is not an indication for therapy. PMID- 1411673 TI - Radiologic manifestations of rheumatic joint diseases in the plain radiograph. AB - In the assessment of radiologic manifestations of joint diseases, rheumatoid arthritis (RA) is the disease to which all others are compared. Knowledge of its characteristics form the basis of the other conditions. To understand the changes seen on the plain radiograph, it is essential to understand its pathophysiology first so that the manifestations of each disease can be appreciated more fully. Due to space constraint, I shall only discuss the main forms of rheumatic joint disease. Other examples of erosive arthropathies, although not rheumatic in origin, will also be included as they form part of the differential diagnosis of an erosive arthropathy, eg gout and psoriasis. PMID- 1411674 TI - A 53-year-old man with atypical chest pain and deep T wave inversion. Apical hypertrophic cardiomyopathy. PMID- 1411675 TI - The first oocyte donation pregnancy home-bred and delivered in Singapore to illustrate a simplified oocyte donation programme--no more embryo freezing, synchronisation or disruption of social life. AB - The wait for an oocyte donor is highly unpredictable and stressful. The recipients may have to remain contactable at all times. Even when a donor is present, their reproductive cycles may not be in synchrony to enable gamete or embryo replacement, and embryo freezing is required for the transfer of embryos in the subsequent cycle. After the release of the Guidelines for Assisted Reproductive Technique by the Ministry of Health we have established a simplified oocyte donation programme with which the need for synchronisation, embryo freezing and the disruption to the recipient couple's social life are eliminated. To illustrate, we report the first report of oocyte donation pregnancy home bred and delivered in Singapore. PMID- 1411676 TI - A successful pregnancy from the oocyte donation programme in Singapore General Hospital. AB - A 41-year-old Chinese woman was seen in our centre in June 1989 with 5 years of premature menopause, requesting ovum donation. She was placed on cyclical hormonal therapy and put on the waiting list for ovum donation. Excess ova became available through one of our IVF patients and were fertilised with her husband's semen. Four pre-embryos resulted and these were cryopreserved using 1,2 propanediol. Embryo transfer in her second cycle of trying on 16 March 1990 of 2 pre-embryos was successful and a singleton pregnancy resulted. The pregnancy was supported with estradiol valerate and intramuscular progesterone till 17 weeks of gestation. The pregnancy went on uneventfully and she delivered a healthy baby boy by Caesarean section on 21 December 1990. PMID- 1411677 TI - Ectopic thymoma: a case for median sternotomy for complete thymectomy. AB - Thymomas are normally found in the superior mediastinum or the upper part of the anterior mediastinum. We report a case of thymoma arising in the inferior aspect of the anterior mediastinum. This case illustrates that thymic tissue may be found low in the anterior mediastinum and supports the practice of a median sternotomy approach for thorough mediastinal exploration in all cases of thymectomy. PMID- 1411678 TI - A case of cavitating pneumonia in AIDS. AB - Tuberculosis is a common cause of cavitating pneumonia in Singapore. In patients with the human immunodeficiency virus (HIV), cavitary pneumonias mimicking tuberculosis can mislead the clinician, delaying diagnosis, resulting in increased morbidity. We describe a HIV seropositive patient with cavitating pneumonia in whom the diagnosis of Pneumocystis carinii pneumonia (PCP) was ultimately established only on bronchoscopy. PMID- 1411679 TI - Case report--melanoma of the anorectum. AB - Melanomas of the gastrointestinal tract are rare tumours, the anorectum being the most common site. Anorectal melanomas can pose difficult diagnostic and therapeutic problems. Awareness on the part of both the clinician and histopathologist that melanomas can rarely occur in the anorectum is an important pre-requisite to its diagnosis as specific histopathological staining may be required. Therapeutically, surgery remains the primary option. Prognosis is however poor as metastatic disease is commonly established at presentation. When the tumour is sited in the rectum, the cells of origin is controversial. A case of disseminated anorectal melanoma is described. PMID- 1411680 TI - Left bundle branch block and right axis deviation due to severe coronary heart disease. AB - The simultaneous occurrence of left bundle branch block and right axis deviation is very rare and occurs mainly in patients with cardiomyopathy. This paper describes a 61-year-old man with end stage ischaemic heart disease who presented with this unique electrocardiographic abnormality. PMID- 1411681 TI - Adult parameningeal rhabdomyosarcoma--a case report and literature review. AB - Although rhabdomyosarcoma is predominantly a malignant disease of children, it is also seen in adults. Since adults account for only 15% of rhabdomyosarcomas, the experience gathered for the treatment of the malignancy has been derived from treating children. The treatment of a case of adult extensive parameningeal rhabdomyosarcoma with CyVADlC chemotherapy and radiotherapy is described, together with a review of the literature. PMID- 1411682 TI - Recurrent cerebral thrombosis associated with protein S deficiency in a Chinese female. AB - A 52-year-old Chinese female with recurrent cerebral thrombosis associated with hereditary protein S deficiency is described. The need to consider clotting disorders in young patients with no known risk factors for stroke is emphasized. PMID- 1411683 TI - The toxic strept syndrome. PMID- 1411684 TI - An epidemic in the field? Rapid assessment procedures and health research. AB - This paper reviews the development of various methods designed to generate relevant social information, pertaining to health and disease control, quickly and accurately. In so doing, we examine the use of KAP surveys and the subsequent development of community diagnosis, rapid appraisal methods, rapid epidemiological assessment, and rapid assessment procedures (RAP) for anthropological studies. Our focus is on the development of anthropological RAPs, in response to the lack of professionally trained social scientists to work with disease control programmes and ministries of health, and in light of the demonstrable need for social science input in the development of health policies and programmes. These developments are assessed in terms of scope and method. Issues relating to the representativeness, reliability and validity of RAP studies are discussed, and mechanisms by which to maximise the yield of valid data are presented. PMID- 1411685 TI - Immunization coverage, infant morbidity and infant mortality in Freetown, Sierra Leone. AB - The study, which is based on data from a household level health survey conducted in 1990 in Freetown, Sierra Leone, examines the coverage of an Expanded Program on Immunization (EPI), infant mortality, and infant morbidity among children in Greater Freetown, capital of Sierra Leone. The results of the study indicate that there was a decline in infant mortality in the recent period of the survey, 1988 89, compared to earlier periods. This decline seemed to have been the result of immunization coverage, which considerably increased by 1989-90, reaching above 70% of the children under age 5. The study further reveals that the increased immunization coverage of children and their mothers might have considerably reduced the incidence of tetanus. While reduction of tetanus might have played the leading role in the latest reduction in infant mortality, the incidence of diarrhea, measles, and malaria continued to be high, suggesting that the increase in the quality and quantity of basic immunizations, oral therapy for diarrheal disease, and provision of chloroquine and improved drugs for malaria disease could further reduce most of the deaths from these prevailing diseases among children under age 5. PMID- 1411686 TI - Global budgeting of hospitals in Hong Kong. AB - Policy-makers in industrialized countries face the dilemma of having to contain soaring hospital costs while resisting any reduction in the quality and quantity of hospital services. Among the many hospital financing systems, centralized control via global budgeting is advocated by some to be the most effective in containing hospital costs. Containing hospital costs, however, is but one aspect of the trade-off between cost containment and quality of care. The hospital financing system of Hong Kong provides some insights into the extent to which cost control can be achieved through global budgeting; and its impact on the accessibility of hospital care. The case of Hong Kong highlights three necessary conditions for effective cost control: (1) the payer must have a clear policy stance on overall public spending; (2) the payer must have a clear policy stance on the importance of hospital care relative to other goods and services; and (3) the payer must also have the will and ability to limit hospital spending within finalized global budgets. However, successful cost containment in Hong Kong affects the accessibility of hospital care. In a time of population growth and economic prosperity, new community needs seem to have preceded government plans and actions to build hospital facilities. PMID- 1411687 TI - The psychological and social condition of hypertensives resistant to pharmacological treatment. AB - To characterize patients with therapy-resistant essential hypertension (TR) from a psychosocial point of view, 29 hypertensives, filling specified criteria for TR in a hypertension clinic were selected out of 800 patients screened. A control group of patients with established, but well controlled hypertension, pair-wise matching study patients for age and gender was also selected. TR patients were predominantly of working-class origin (68 vs 19% P less than 0.001). They tended to be more obese (BMI 28.7 +/- 5.5 vs 26.9 +/- 3.9 ns). TR tended to report fewer important life events, and reported significantly fewer positive events from the last 10 year period P less than 0.05. According to the EAI, their ability to channel emotions, especially anger, was impaired (P less than 0.01). So was their instrumental handling of emotions such as anger and sorrow (P less than 0.05). They experienced less of joy, and even had a more negative attitude towards that emotion (P less than 0.05). When adjusted for social class this latter difference was not statistically significant. Their degree of global emotional differentiation was lower (P less than 0.05). In the ISSI interview they had low scores for availability of emotional attachment (P less than 0.01), and friendship (P less than 0.05), but not for social integration. To conclude, when compared to well controlled hypertensives, TR exhibited the pattern, which has been shown to characterize young, asymptomatic, hypertensives in comparison to healthy subjects. These results must not be overinterpreted due to the limited sample.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411688 TI - Re-assessing disability: the impact of schistosomal infection on daily activities among women in Gezira Province, Sudan. AB - Schistosoma mansoni is often perceived by governments and international aid agencies to present a major public health problem in the tropical and sub tropical world. This perception persists in spite of the fact that biomedical practitioners and research workers disagree about the nature and extent of disease and disability caused by schistosomes. This paper raises the question of whether S. mansoni should continue to be given priority as a public health problem in Gezira Province, Sudan. Biomedical and continuous observational data are blended with ethnographic information in order to develop a more integrated picture of the impact of S. mansoni on daily activity patterns among women. Research took place in one village in the Gezira/Managil irrigation scheme. The study is characterized by a small sample and a paired design. That is, 11 infected women were paired with 11 uninfected women. These women were engaged in agricultural activities in the cotton picking season and they were matched for a wide range of social and economic factors that might otherwise have affected their working activities. Observations were conducted on a minute by minute basis in the cotton fields. These data, in combination with ethnographic information and data indicating female productive output, showed that infection with S. mansoni significantly altered activity patterns in the cotton fields. That is, infected women (with an arithmetic mean egg output of 1958 eggs/g) attempted to pick as much cotton as possible in the shortest time period feasible in the morning. This pattern was partially repeated by infected women who returned to the fields in the afternoon. However, a significant number of infected women felt too weak to sustain this work regime and the economic implications of this finding are discussed. Finally, Fisher's exact probability test showed that infected women were significantly less likely to undertake personal care activities between cotton picking sessions and this result suggests they may have been too tired and/or had a diminished perception of their own well-being. The implications of these results for public health policy in Gezira Province are discussed. PMID- 1411689 TI - Mother sold food, daughter sells her body: the cultural continuity of prostitution. AB - This article provides a cultural interpretation of female prostitution in contemporary lowland Buddhist Thai society. The heterosexual transmission of AIDS through prostitution has exposed the shallowness of our understanding of prostitution as a sociocultural phenomenon. The data were collected through case studies, participant-observation, and review of Thai language media and texts. It is argued that in the past decade or so, the simultaneous rapid growth of prostitution as a lucrative sex industry and of the Thai economy as an emerging newly industrialized country (NIC) have, paradoxically, enabled female prostitutes to conserve the basic institutions of society. This has occurred at a time when landlessness, rampant commercialism and poverty have threatened the survival of traditional lifeways among the majority rural agricultural population. Prostitution, although illegal, has flourished at least in part because it enables women, through remittances home and merit-making activities, to fulfil traditional cultural functions of daughters, conserving the institutions of family and village-level Buddhism, as well as of government. PMID- 1411690 TI - Oral contraceptive marketing in Ibadan, Nigeria. AB - The demographic transition in Nigeria is gradually moving towards the second stage. There is clear evidence of a declining mortality but the fertility rate remains exceptionally high. A realistic approach towards reducing fertility rate is the use of oral contraceptive. This study assesses the distribution system of oral contraceptive in Ibadan, the second largest city in Nigeria. The findings revealed that the people are aware of modern oral contraceptives as they purchase them freely at chemist shops. But effective distribution is hampered by existing channels and high costs. A local source recommended is the proprietary medicine stores, often at convenient locations to the potential users of contraceptives. The current cost which is between $1.3 and $19.5 per couple-years of protection is exorbitant, consuming 0.5-7.8% of the gross annual income of the average individual. Therefore, the government should subsidize the prices of oral contraceptives, to facilitate freedom from the tyranny of excessive fertility. PMID- 1411691 TI - Artificial donor insemination in Yaounde: some socio-cultural considerations. AB - Infertility affects about 14% of the population in Cameroon. The majority of those affected are between 26-30 years old. Between 40-50% of all cases of infertility are associated with male failure, and azoospermia is implicated in 14.4% of the cases. There is thus an indication for assisted reproduction among this category of infertile couples particularly artificial insemination by donor (A.I.D.). A comparative study on fertile and infertile couples' perception of A.I.D. revealed that knowledge of A.I.D. is low, 35.30% of infertile respondents were aware of the procedure via a vis 30.6% of their fertile counterparts. Nonetheless 49% of infertile respondents accepted A.I.D. in principle compared to 37.75% of their fertile counterparts. Despite the high value respondents placed on having children and the strong desire by infertile couples to have their reproductive potentials fulfilled, only 19.6% of infertile respondents and 42.87% of their fertile counterparts respectively, would actually practice A.I.D. if the need arose. There are indications that respondents did not perceive A.I.D. as an acceptable solution to infertility. Evidently, the possible influence of socio cultural barriers to A.I.D. as well as perceived socio-cultural alternatives which may be more acceptable to infertile couples than a technically assisted form of reproduction, have been overlooked. PMID- 1411692 TI - Marital status, fatness and obesity. AB - Marital status is related to morbidity and mortality, with married people healthier and at lower risk of death than those who are unmarried (especially among men). However, the relationship between marital status and obesity is not well established. Role theory suggests through a marital causation model that people in the marital role are more likely to be obese, and through a marital selection model that people in the marital role are less likely to be obese because of stigmatization. The martial causation model was examined using data from the National Survey of Personal Health Practices and Consequences, a cross sectional national telephone survey of 3025 adults age 20-64 in the United States. Sequential regression analyses revealed that married men were significantly fatter and more likely to be obese than never married or previously married men, even when demographic, social, and physical variables were controlled. By contrast, marital status was not significantly associated with fatness or obesity among women when other variables were controlled. The marital role appears to influence fatness and obesity among men, but not women. PMID- 1411693 TI - His and hers: male and female anatomy in anatomy texts for U.S. medical students, 1890-1989. AB - Much recent work on gender has emphasized how ideas of male and female differences underlie cultural assumptions about appropriate social relations, behavior, institutions and knowledge. This study focuses on the specific ways that anatomy texts for medical students in the United States have presented male and female anatomy between 1890 and 1989, using both numerical data and analysis of textual examples from 31 texts. Despite public debates about gender representation, anatomy texts have generally remained consistent in how 'the' human body has been depicted in this century. In illustrations, vocabulary and syntax, these texts primarily depict male anatomy as the norm or standard against which female structures are compared. Modern texts thus continue long-standing historical conventions in which male anatomy provides the basic model for 'the' human body. PMID- 1411694 TI - Self-assessed health among Norwegian adults. AB - Previous research has used self-assessed health as a proxy for 'objective' health rating as an important element in sick role behaviour, as well as a predictor of life satisfaction and mortality. However, several authors have suggested that self-evaluations of health are not only reflections of the underlying medical condition. It has been claimed that personal and social background characteristics such as sex, age, race, and occupational status contribute independently to subjectively appraised health. The present article uses data from a large, nation-wide sample of Norwegian adults (N = 7302) to estimate the relative predictive power of 'medical' variables (number and duration of illness episodes, diagnosis, functional impairment) on the one hand and 'socio-cultural' variables (age, sex, socio-economic status, type of work, income, household composition/life cycle) on the other. It is concluded that when a sufficiently fine-grained array of medical information is available, socio-cultural factors contribute only marginally to self-assessments of health. PMID- 1411695 TI - Sickness Impact Profile: the state of the art of a generic functional status measure. AB - The Sickness Impact Profile (SIP) is a widely used health status measure, known to be valid and reliable. After the final development and testing in 1978, however, in which several methodological aspects were investigated, no descriptions of research projects that systematically evaluate the methodological and theoretical aspects of the instrument were found. In this article a review is presented of literature on the SIP. This review is the first step taken in a project that evaluates the SIP. The instrument appears to be a reliable instrument with sufficient content validity. It shows good correlations with other health status and functional status measures. Yet a number of questions about the SIP remain unanswered. Theoretical implications of the construct of sickness, the effect of age and gender on SIP scores, the construct validity judged by factor analysis, the responsiveness of the instrument, and the possibilities to use proxy-respondents or to shorten the list and to simplify the scoring procedure still have to be studied. If the instrument is to be used as an international standard measure of functional status, these topics should be thoroughly examined. PMID- 1411696 TI - Drug retailer training: experiences from Nepal. AB - Sale of modern medicines by untrained peddlers, general merchants, and other drug sellers is common throughout the developing world. Drug sellers operating in the 'informal sector' are often the first source of health care outside the home. Reasons given by patients for using private drug sellers include expediency, convenience, efficacy of the medicines, dependability of supply, and reasonable cost. At the same time, self-medication through private drug sellers can be ineffective, wasteful, and at times distinctly harmful. Regulatory approaches to controlling drug selling in the informal sector, widely endorsed on paper through national drug control legislation, require a cadre of professional regulatory staff and enforcement mechanisms which are too often beyond the current economic and political reach of countries. In Nepal, where rugged terrain has limited infrastructure development, the doctor to population ratio is 1:23,000, utilization of government health services averages only 0.2 visits per person per year. Retail drug outlets outnumber health posts and health centers by a ratio of 4:1 and private drug sellers often offer the only access to modern medicine for much of the population. Community surveys have found that drug retailers are very often the first and only source of health care outside the home. Given the importance of retail drug outlets and the lack of trained pharmacists, the Department of Drug Administration in 1981 established a 45-hr course for drug retailers which emphasized practical training as well as formal teaching on pharmacology, ethics, storage of drugs, and legal issues. By the end of 1989, 4096 drug retailers had graduated from the course. Still run by the Ministry of Health Department of Drug Administration, the course has proven to be administratively feasible and has been quite popular with drug retailers. Initial reservations expressed by doctors and some pharmacists were soon overcome, and the course is now well accepted by professional groups. Because the course is offered in different locations, geographic coverage has also been very good despite Nepal's logistic constraints. The operating cost of the course averages about U.S. $18 per trainee. Informal evaluations have resulted in plans for refresher training more narrowly focused on safe dispensing and appropriate referral for a limited number of important public health problems. Since 50-90% of pharmaceutical expenditures typically pass through the informal private sector in developing countries, it is suggested that other countries consider focused drug retailer training as a response to the problems of manpower shortages and drug dispensing by unqualified staff. PMID- 1411697 TI - Deriving a survey measure of social support: the reliability and validity of the Close Persons Questionnaire. AB - The development of a new questionnaire to measure social support, the Close Persons Questionnaire is described from the Whitehall II Study, a longitudinal study of the impact of psychosocial factors on health. The Close Persons Questionnaire includes items on three types of support from up to four nominated close persons and social networks. Its repeatability over a four week period and its validity against the Self Evaluation and Social Support Interview is reported in a sample of British Civil Servants. The difficulties of satisfactorily validating measures of social support are discussed. PMID- 1411698 TI - The use of herbal and other agents to enhance sexual experience. AB - This study examines the use of herbal and other agents prior to sexual intercourse. This practice is thought to be common in central and southern Africa. The study comprises an analysis of the behavioural and psychological aspects of the practice. Structured interviews were conducted with 63 Zimbabwean women, 33 were attenders at an urban health clinic, 30 were nurses. Eighty-seven percent of the sample reported using herbs and other agents regularly as a preparation for sexual intercourse. The health and social consequences of such practices are examined; the problems of cervical cancer and HIV and their relation to these practices is discussed. PMID- 1411699 TI - Mothers' fear of child death due to acute diarrhoea: a study in urban and rural communities in northern Punjab, Pakistan. AB - The investigation of cultural models of diarrhoeal illness which are employed by mothers and their emotional responses to children's illnesses is presented in a study of 595 households in urban and rural communities in Punjab, Pakistan. The household survey of mothers of children 0-36 months was complemented with in depth interviews of a subsample of 70 mothers. Findings indicate that diarrhoea must be regarded not only as a disease but as a symptom belonging to several popular illness categories. Mothers' emotional responses to symptoms are in part shaped by the illness categories to which they assign a child's diarrhoea episode, and maternal fears that symptoms of diarrhoea may be life threatening are associated with previous experiences with death of children, with treatment choices and help-seeking. A significantly higher proportion of mothers who fear diarrhoea to be life threatening to their children than mothers with other concerns choose to use NIMKOL, the Pakistan ORS. The necessity of recognizing the complexity of interpretive and emotional processes which shape the care of children and the home treatment of childhood disease is emphasized. PMID- 1411700 TI - The effects of variations in AFDC and Medicaid eligibility on prenatal care use. AB - Despite substantial evidence linking improved pregnancy outcomes with receipt of prenatal care and recent improvements in prenatal care utilization, specific subpopulations continue to receive less than adequate care. The study reported here examined the effects on prenatal care utilization of differences among states in AFDC and Medicaid eligibility policies. The study was based on information obtained from birth certificates and a mailed questionnaire to stratified random samples of all women experiencing live births during specified periods in four states. States were selected to provide comparisons between two states with liberal AFDC and Medicaid eligibility standards--Wisconsin and Colorado--and two states--Maine and Texas--which had more restrictive standards at the time data were collected. Study findings generally indicate that more liberal AFDC/Medicaid eligibility standards improve the adequacy of prenatal care among low income women. They also suggest, however, that the often lengthy eligibility process may actually pose barriers to care. PMID- 1411701 TI - Behavior change strategies for family planning. AB - The technology of behavior modification is central to most family planning and population control strategies. Positive, differential and negative reinforcement, usually cast in terms of 'incentives' and 'disincentives', have been applied to promoting child spacing and contraceptive use throughout the developing world. A wide variety of options are available to program planners interested in decreased birth rates, increased contraceptive use and/or birth spacing, and general promotion of family planning behavior. Given the tremendous problems with overpopulation and maternal/child health in developing nations today, behavior modification techniques are proposed specifically as the most effective way to motivate behavior change in the area of birth planning. These techniques also provide a useful framework with which to classify current family planning strategies and maximize their overall effectiveness. Given the powerful potential of this technology, understanding relevant ethical considerations and limitations is of paramount importance. PMID- 1411702 TI - Discrimination towards disabled people seeking employment. AB - This research was undertaken to determine whether or not disabled persons are at a disadvantage when seeking employment. An experimental design--mailing unsolicited job applications to employers--in a natural social setting allowed a study of employer's behaviour under naturalistic conditions. A randomized comparative study was conducted on a representative sample of 2228 branches of French companies, stratified as a function of their size. Four different profiles of applications were constituted by crossing two independent variables: the presence or absence of mention of a physical deficiency (paraplegia, with a wheelchair) in the job application, and high or low level of qualification. Using random sampling, the investigators sent each company an application for a job using one of these four profiles. Two experimental groups of companies were constituted (each of which received an application with either high or low qualification and mention of disability) with two control groups (applications with high/low qualification, without mention of disability). It was found that highly qualified able-bodied applicants were 1.78 times more likely to receive a favorable response than their disabled counterparts, and modestly qualified able bodied applicants were 3.2 times more likely to receive a positive response. As well, discrimination became more marked as company size increased. In comparison with laboratory experiments, the results of this research permit a more objective assessment of discriminatory behaviour by companies confronted by disabled job applicants, and show a significant amount of discrimination towards individuals with a physical disability. PMID- 1411703 TI - Sociology in American medical education since the 1960s: the rhetoric or reform. AB - Despite recommendations by medical reformers that medical sociology be included in the curriculum, there is currently little evidence of a far-reaching integration of sociological perspectives in American medical education. Yet, support for the relevance of sociological knowledge has since the late 1960s helped to diffuse external pressures for change in health care and medical education. As a symbol of the communitarian commitment of the medical profession, claims in favor of the incorporation of sociological perspectives have thus occasionally, and largely unintentionally, served the public relations interests of biomedicine. However, the more recent interest in medical ethics has to some degree transformed medicine's educational agenda and the definition of medical 'human values'. Whereas the rhetorical expropriation of medical sociology primarily has concerned medicine's responsibility vis-a-vis society as a whole, the new medical ethics education signifies a return to a more individualistically oriented medical morality. PMID- 1411704 TI - Maternal health and the measurement trap. AB - This paper focuses on the contribution of measurement-related factors to the neglect of maternal health in resource allocation for programmes and in public health research. As the recent interest in maternal health has now progressed beyond the need for information primarily for the purpose of advocacy, measurement-related factors have emerged as powerful constraints on programme action. Three outstanding needs for information can be identified: first, to establish the levels and trends of specific maternal health outcomes; secondly, to identify the characteristics and determinants of health outcomes; and thirdly, to monitor and evaluate the effectiveness of programmes designed to influence health outcomes. In order to meet these needs, the emphasis placed on operational research by the current major initiatives in maternal health must be complemented by an equivalent emphasis on methodological studies. The call for improved information by international and national agencies should be made in unison with the call for action. Inadequate information is a reality that has to be faced throughout the world, but particularly in developing countries. The quality, quantity and scope of health-related data are the elements of this inadequacy and may be discussed in terms of four factors: the indicators, the data sources, the measurement techniques, and the conceptual framework. In this paper, the neglect of maternal health and the lack of information are shown to be self-reinforcing and constitute a measurement trap sprung by these four factors. Dismantling this trap has revealed a weak conceptual framework to lie at the very centre. Maternal health has tended to be conceptualized as a discrete, negative state, characterized by physical rather than social or mental manifestations, and by a narrow time-perspective focusing on pregnancy, delivery and the puerperium. The need to broaden this perspective and to develop equally broad operational definitions represent important steps forward that must be taken. PMID- 1411705 TI - Costs of home care for advanced breast and cervical cancer in relation to cost effectiveness of screening. AB - The costs of home care in the Netherlands are estimated for women with advanced breast and cervical cancer. We observe a growing role of intensive home care for the terminally ill patients. The average costs of home care are dfl 8,500 per patient for breast cancer patients and dfl 7,200 for cervical cancer patients. More than half of these costs are incurred in the last month before death. The level of home care in the preceding months is quite modest (dfl 120 per month for both diseases), not taking into account informal care. The costs of home care for patients with advanced cancer are only slightly related to the site of the primary tumor from which the metastases originate. Total average costs per patient during advanced disease, including hospital and nursing home care, amount to dfl 42,700 for breast cancer and dfl 29,000 for cervical cancer. This difference in costs is largely attributable to the longer duration of advanced disease for breast cancer, which substantially affects hospital costs. The high costs of care to patients with advanced cancer contribute to a favourable cost effectiveness ratio of those screening programmes which reduce mortality and consequently the costs of care to advanced cancer patients. PMID- 1411706 TI - Primary care in accident and emergency and general practice: a comparison. AB - This paper reviews the way in which literature describing 'inappropriate' attenders at Accident and Emergency (A & E) departments in Britain has suggested that they could be provided for in General Practice and that their attendance at A & E departments therefore implies a 'failure' of general practice in urban areas. One problem with much previous research is that 'inappropriate' attenders have been retrospectively identified. The comparative survey of attenders at a London A & E department and patients visiting their GP in the same district reported here prospectively identified A & E attenders with primary care problems and examined the differences between them and the GP attenders. Patients attending the hospital A & E department were similar to the GP attenders in terms of socio-economic indicators, but had problems which were not typical of the general practice workload and were in different circumstances. The results suggest that there will be a continuing demand for hospital-provided primary care in urban areas, and that attempts to deflect such care to the community will meet with limited success. PMID- 1411707 TI - Regular pattern of preventive dental services--a measure of access. AB - Having a regular pattern of care should be an indicator of access to and periodic use of preventive and health maintenance services. The analyses reported in this study are intended to provide a better understanding of the factors related to having a regular pattern of preventive dental care. The data were collected in 1981 as part of a U.S. household survey, 'A Study of Dental Health Related and Process Outcomes Associated with Prepaid Dental Care', the most comprehensive cross-sectional data base available in dentistry. Descriptive analyses of a constructed variable, representing perceived and realized access and a preventive orientation, indicate that 53% of the population had a regular pattern of preventive care. Those with a regular pattern of care were more likely to be white, younger, have dental insurance, have no cost barriers, have more than 12 years of education, be dentate, have no perceived symptoms, and no fear of pain. Logistic regressions indicated that there was an increased probability of having a regular pattern of preventive care if individuals had no economic access problems, had positive attitudes, had higher income, reported few oral symptoms, and were non-Black. Overall, the descriptive models used suggested that individuals with resources in the form of finances and education, and a sense of self-efficacy as expressed in attitudes toward oral health, had the greatest probability of having a regular pattern of preventive care. PMID- 1411708 TI - Content and context: working with mentally ill people in family therapy. AB - This article addresses the family's experience of caring for a mentally ill family member in the home. The focus is on how the family manages overt psychotic symptoms and the resulting interpersonal stresses. A model of intervention is proposed that allows therapists and families to examine the content and context of the psychotic material and to intervene in nonthreatening ways. This model has its base in psychoeducation and communications theory. The effectiveness of the content and context model is developed through the analysis of two case examples. The cases show the intervention to be helpful in decreasing family stress and in establishing empathic awareness between the family and the ill member. Implications for adapting this model to the psychoeducational model with the goal of enhancing the family's caretaking role are reviewed. PMID- 1411709 TI - Burnout in hospital social workers who work with AIDS patients. AB - Fears of a future shortage of experienced social workers in the acquired immune deficiency syndrome (AIDS) field because of burnout prompted this study of 128 hospital social workers who work with AIDS patients. Results show that hospital AIDS social workers had slightly higher rates of emotional exhaustion and depersonalization on the Maslach Burnout Inventory but also felt a substantially higher level of personal accomplishment. Age, autonomy, and belonging to a support group explained 19 percent of the variance in burnout. Hospital administrators are urged to examine their administrative policies concerning these factors and to explore ways to preserve and enhance the most satisfying aspects of the work. Further research is encouraged to explore the relationship between young age and burnout and to better understand the factors that make AIDS work satisfying. PMID- 1411710 TI - Preventing AIDS among black gay men and black gay and heterosexual male intravenous drug users. AB - The black population is disproportionately affected by acquired immune deficiency syndrome (AIDS). Among those black people most at risk of becoming infected with the human immunodeficiency virus are black men who use intravenous drugs and black men who are gay. This article explores the complex cultural, economic, and social factors obstructing the reduction of the AIDS rate among these men. Implications and recommendations are made for developing effective AIDS prevention efforts by highlighting race-specific resources and supports for high risk black men. PMID- 1411711 TI - "Chronic fatigue syndrome and women: can therapy help?". PMID- 1411712 TI - "Chronic fatigue syndrome and women: can therapy help?". PMID- 1411713 TI - "Chronic fatigue syndrome and women: can therapy help?". PMID- 1411714 TI - Article makes eloquent statement. PMID- 1411715 TI - Grand rounds revisited: some comments on current practices. PMID- 1411716 TI - Isolated splenic metastasis from rectal carcinoma. AB - Splenic metastasis is a late manifestation of disseminated disease. Focal metastatic splenic involvement, however, without evidence of additional systemic disease, is unique. Review of the literature yielded only one case of isolated splenic metastasis incidental to rectal carcinoma. We have reported an additional case of isolated solitary splenic metastasis from primary adenocarcinoma of the rectum. Theoretically, certain anatomic, histologic, and functional splenic attributes may limit splenic involvement from metastatic disease. PMID- 1411717 TI - Acute pancreatitis due to sulfamethoxazole-trimethoprim. AB - We have reported a case of sulfonamide-induced acute pancreatitis. A review of the literature showed only eight previously reported cases. Adverse reactions to sulfonamides are well known, but acute pancreatitis is a very serious complication. If evidence of pancreatic involvement occurs during sulfonamide therapy, the medication should be discontinued immediately and, if necessary, be replaced by an alternative. Other causes of pancreatitis must be excluded. PMID- 1411719 TI - Delayed CSF seeding of benign oligodendroglioma. AB - We report the case of a man who at 42 years of age had right frontal lobectomy for removal of a benign oligodendroglioma. Seventeen years later, at age 60, he had resection of a fourth ventricular vermian lesion, which was found to be histologically identical to the original lesion. A further lesion in the left occipital lobe was not biopsied but was treated with radiation therapy. We suggest that these subsequent two neoplasms represent CSF spread of the original tumor. This case emphasizes the need for indefinite longitudinal surveillance for these patients. PMID- 1411718 TI - Hyperprolactinemia in a patient with Sheehan's syndrome. AB - I have reported the case of a woman with Sheehan's syndrome who had hyperprolactinemia rather than prolactin deficiency. The patient showed no increase in serum thyrotropin in response to TRH challenge and failed to show a normal increase in serum GH and cortisol after insulin-induced hypoglycemia. A blunted FSH response to LH-RH stimulation was also found. A CT scan of the sella showed no adenoma. The patient responded to prednisolone and thyroxine replacement therapy. When, a few months later, the dose of thyroxine was reduced to a suboptimal level, the hyperprolactinemia recurred. PMID- 1411720 TI - Recurrent pneumococcal pneumonia in an HIV-positive patient with lymphoid interstitial pneumonitis. AB - Lymphoid interstitial pneumonitis (LIP) is a rare complication of AIDS in adults. Patients with AIDS and LIP are at high risk for bacterial pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. We have described an HIV-positive patient with LIP complicated by recurrent pneumonia due to Streptococcus pneumoniae; recurrence was apparently prevented by maintenance penicillin therapy. PMID- 1411721 TI - Elective transtracheal jet ventilation for bronchoscopic removal of tracheal foreign body. AB - We have shown that transtracheal jet ventilation can be used safely and effectively when removing a foreign body from the airway. In some cases, it may be wise to choose this method of ventilation initially, thus avoiding the difficulties associated with more conventional modes of controlled ventilation. This is especially true when the potential for loss of the airway during the procedure is significant. This technique also allows the bronchoscopist the benefit of unimpeded access to the airway and adequate uninterrupted time for his operative procedure. PMID- 1411722 TI - Complications of trichobezoars: a 30-year experience. AB - We have reported the case of a mildly retarded woman in whom an obsessive compulsive disorder of hair eating (trichophagia) had begun between 2 and 3 years of age. Over the next 30 years, multiple complications of trichophagia included trichobezoars, malnutrition, intestinal obstruction, and ulceration with bleeding. One of the bouts of intestinal obstruction was associated with the superior mesenteric artery blocking the duodenum. This complication has not been reported previously in this disorder. The patient's trichotillomania (hair pulling) was treated with psychotherapy, behavior modification, and various medications, without success. The tricyclic antidepressant clomipramine (Anafranil) may be of benefit in such cases. PMID- 1411723 TI - Diffuse pulmonary tumor microemboli from adenocarcinoma of the colon. AB - We have presented a rare case of pulmonary tumor microemboli from adenocarcinoma of the colon. The majority of primary tumors are adenocarcinomas, with gastric, breast, and liver carcinomas most frequently identified. Dyspnea and respiratory distress without an obvious cause is common. The history, physical examination, chest roentgenogram, ventilation-perfusion lung scan, and pulmonary angiogram are often not helpful in establishing the diagnosis. Pulmonary hypertension, present in our patient, and cor pulmonale are well described in association with diffuse pulmonary tumor microemboli. The pathologic findings are limited to the intravascular compartment exclusively, frequently in association with thrombus. The true incidence of pulmonary tumor microemboli is not known and may be underestimated. Appropriate management requires a high index of suspicion to establish the diagnosis. PMID- 1411724 TI - Recurrence of neisserial meningococcemia due to deficiency of terminal complement component. AB - Recurrent infections with Neisseria meningitidis are attributed to deficiencies of terminal complement components. The serotype most commonly responsible for recurrent N meningitidis infections is serotype Y. We have reported a case of recurrent meningitis due to N meningitidis in a patient who was found to be deficient in the sixth component of complement. Complement deficiencies should be considered in any patient with recurrent infections caused by N meningitidis. PMID- 1411725 TI - Solitary rectal ulcer syndrome: not always ulcerated. AB - Our patient had a nonulcerated rectal lesion grossly resembling a villous tumor, but microscopically proving to be a solitary rectal ulcer. We have discussed the clinical and pathologic findings and the probable relationship of the lesion to straining at the stool. PMID- 1411726 TI - Transmission of AIDS. PMID- 1411727 TI - Transmission of AIDS. PMID- 1411728 TI - Endocarditis in drug abusers. PMID- 1411729 TI - Vocal cord dysfunction. PMID- 1411730 TI - There is no current indication for laparoscopic adhesiolysis to treat abdominal pain. PMID- 1411731 TI - Laparoscopic cholecystectomy: a community experience. AB - Minimally invasive surgery appears to be gaining popularity, and removal of the gallbladder by laparoscopic methods is one such procedure for which there is recent enthusiasm. The concerns about safety, morbidity, and mortality in contrast to standard cholecystectomy are being evaluated. To address these concerns we reviewed the first 230 laparoscopic cholecystectomies done by one surgical group from October 1990 to September 1991. There were 161 women and 69 men with an average age of 50 years. The average length of stay was 2.1 days, most patients being discharged in 24 hours. Complications occurred in 14 patients (6%). The one death was unrelated to the gallbladder surgery. Operative cholangiograms were done as frequently as possible. It appears that laparoscopic cholecystectomy can be done safely and with a shorter hospital stay. Complications are similar to those seen with standard cholecystectomy. PMID- 1411732 TI - Esophagogastric ring: why and when we see it, and what it implies: a radiologic pathologic correlation. AB - Schatzki first reported a ring-like structure at the esophagogastric mucosal junction in 1953. There is still no uniform agreement as to its exact location, etiology, or clinical importance. We found an esophagogastric ring in 15% to 18% of 22,368 patients having routine upper gastrointestinal examinations. It was present only in patients with cephalad displacement of the esophagogastric junction and only in those who had sharply and circumferentially marginated transition of esophagogastric mucosal junction. It is postulated that the esophagus shortens on vagal stimulation by contracture of the longitudinal esophageal muscle, which causes a mucosal infolding at the esophagogastric junction. In a small group of these patients, fibrosis apparently develops in this region and results in a fixed organic circumferential diaphragm, which may cause obstructive symptoms. These concepts affect therapeutic alternatives. PMID- 1411733 TI - Race-related differences in metabolic control among adults with diabetes. AB - The effect of race on differences in metabolic control was examined in patients with non-insulin-dependent (NIDDM) and insulin-dependent (IDDM) diabetes mellitus. Data were collected on HbA1c, age, duration of diabetes, age at onset, family function, stress, body mass index, waist/hip ratio, total cholesterol, insulin dose, diet, and physical activity. Among those with NIDDM, black patients had significantly higher HbA1c levels than their white counterparts. This difference persisted after adjustment for covariates. Among patients with IDDM, black subjects were found to have higher HbA1c levels, body mass index, and total cholesterol levels than their white counterparts. After correction for diabetes duration, relative insulin dose, physical activity, body mass index, and cholesterol, black women had significantly higher HbA1c levels than black men, white men, or white women. We conclude that race and sex differences do affect the metabolic control of patients with diabetes mellitus. PMID- 1411734 TI - Listerial infections in patients with systemic lupus erythematosus. AB - Infection with Listeria monocytogenes is known to occur more frequently in immunosuppressed patients, including those receiving high-dose prednisone or cytotoxic therapy for collagen vascular disease. We reviewed three cases of listeriosis and systemic lupus erythematosus (SLE) seen at our institution, in addition to five cases reported in the English literature. Seven of the eight patients had non-CNS listerial infections. All patients but one had associated risk factors of either renal failure or pregnancy. From our review, we found that listeriosis is uncommon in SLE, and patients without renal failure or pregnancy do not seem to be at increased risk for listeriosis. Although most patients were treated with high-dose prednisone, with or without cytotoxic drugs, the role of immunosuppression by these drugs as a risk factor for listeriosis remained unclear. PMID- 1411735 TI - Archery-related injuries of the hand, forearm, and elbow. AB - The five patients reported herein had various archery-related injuries of the upper extremities. Acute injuries included arrow laceration of a digital nerve and artery, contusion of forearm skin and subcutaneous tissue, and compression neuropathy of digital nerves from the bowstring. Chronic injuries included bilateral medial epicondylitis and median nerve compression at the wrist, de Quervain's tenosynovitis, and median nerve compression at the elbow. Essential measures for archery safety include use of archery protective gear, use of a light-weight bow, conditioning of the forearm flexor muscles, and modifications in drawing the bowstring. PMID- 1411736 TI - Victims of crime: the internist's role in treatment. AB - This article reports a case study on a crime victim identified and treated in an internal medicine residency program. Recent findings on crime and violence in the United States are reviewed with a particular focus on the psychologic and medical aftermath faced by victims. A unique role for the internist is suggested in the management of such sequelae. Research studies suggest that victims of crime, especially violent crime, evidence one or more of several clusters of acute and delayed emotional responses that typically progress through three stages of a recovery process. Physician awareness of these symptom clusters should result in increased understanding and improved assessment/treatment of crime victims. PMID- 1411738 TI - Changes in residents' attitudes in response to residency program modifications: a prospective study. AB - Interventions to modify stress during residency training have rarely been formally analyzed for effectiveness. Using a 33-item, closed-ended questionnaire based on factors previously reported to cause residency stress, we studied how program modifications affected the attitudes of residents in a university affiliated community internal medicine residency training program. Training program modifications, targeting specific questions, were prospectively introduced, and questionnaire responses were compared from year to year and by resident year of training. Between 1988 and 1989, the noon conferences and ward rotations were modified. Between 1989 and 1990, a "night float" was introduced. Residents' responses varied little by year of training, but the mean responses to seven of the fourteen "targeted" questions showed significant changes over time. In particular, the introduction of a night float resulted in markedly improved attitudes regarding time demands. This study demonstrates that residents' attitudes can be objectively measured, and that residents accurately perceive and respond to program modifications. Efforts should be made to standardize, validate, and develop attitudinal scales from such questionnaires to aid in the assessment of the numerous changes in residency programs currently being considered or implemented nationwide. PMID- 1411737 TI - HIV seroprevalence in hospital patients in rural Georgia. AB - To determine human immunodeficiency virus (HIV) seroprevalence among hospital patients in three rural community-based hospitals in southern Georgia, we anonymously tested patients 15 to 54 years old for antibodies to HIV-1 from residual blood specimens collected for routine diagnostic purposes. Data collected included age, sex, race, hospital service, presenting condition, physician's knowledge of HIV infection status, and discharge diagnosis. Of 1319 patients tested, seven (0.5%, 95% confidence interval = 0.2% to 1.1%) had antibodies to HIV-1. Of those seven, five had HIV infection unsuspected by their physicians, and four had an infectious disease. HIV seroprevalence was 0.5% for both men and women, 1.0% for blacks, and 0.3% for whites. HIV-positive patients were found on all hospital services. These results suggest that in rural southern Georgia hospitals, HIV should be routinely considered in the differential diagnosis of conditions that may be related to HIV. In addition, these data demonstrate a need for medical services or referral networks for HIV-related illnesses and a need for continuing HIV counseling and testing offered by local health departments in rural southern Georgia. PMID- 1411739 TI - Wandering spleen: anatomic and radiologic considerations. AB - Wandering spleen is a rare clinical entity and remains an elusive clinical diagnosis, particularly in the pediatric patient. Among the imaging modalities (computerized tomography, magnetic resonance imaging, nuclear medicine, ultrasonography, plain films) used in the diagnosis of wandering spleen, ultrasonography is the least invasive and most effective. Elective splenopexy remains the treatment of choice when the diagnosis is made before splenic infarction. We present two cases of wandering spleen manifested as a lower abdominal mass, and we discuss the surgical anatomy of the spleen and splenic ligaments and the hypothetical responsibility of these ligaments for the genesis of this clinical entity. PMID- 1411741 TI - To preach or teach: empowering patients and the health care crisis. PMID- 1411740 TI - Methylphenidate hydrochloride as an antidepressant: controversy, case studies, and review. AB - The use of psychostimulants as antidepressants remains controversial in the field of psychiatry. While methylphenidate hydrochloride (MPH) and dextroamphetamine (DA) are often considered to be equivalent drugs, differences in their neurobiologic mechanism of action may account for different clinical response patterns. Hence, clinical trials and literature reviews that examine the antidepressant efficacy of psychostimulants without distinguishing between MPH and DA may reach inaccurate conclusions. This paper is a critical review of controlled and uncontrolled studies examining the use of MPH as an antidepressant. We discuss the methodologic limitations of existing placebo controlled trials that have reached mixed conclusions about the efficacy of MPH as an antidepressant. These studies are offset by uncontrolled open trials and clinical case reports that endorse the drug's effectiveness in alleviating depressive symptoms. The series of patients we treated with MPH demonstrates the safety and efficacy of this drug in alleviating depressive symptoms in the medically ill elderly with a variety of mood disorders. Reviewing these six cases and balancing the positive and negative reports in the literature, we provide practical guidelines for identifying patients who are potential candidates for treatment with MPH. PMID- 1411742 TI - The not-so-immovable object meets the irresistible force. PMID- 1411743 TI - Depressive symptoms and mental health service utilization in a community sample. AB - This study examines the utilization of health visits for mental health purposes by community respondents with depressive symptoms. Data are drawn from first wave interviews of the Epidemiologic Catchment Area (ECA) project at the Baltimore, Durham, and Los Angeles sites. The results indicate that persons with depressive symptoms, even in the absence of a recent DIS/DSM-III disorder, are at increased risk for making mental health related visits. The risk of visiting a general medical provider or mental health specialist for mental health treatment tends to increase as the number of depressive symptoms increase. Sociodemographic factors including age, racial background, and employment status also influence the risk of making a mental health related visit. PMID- 1411744 TI - Comparison of two self administered psychiatric questionnaires (GHQ-12 and SRQ 20) in primary care in Chile. AB - The General Health Questionnaire (GHQ-12) and the Self Report Questionnaire (SRQ 20) were simultaneously validated against the criterion of the Revised Clinical Interview Schedule (CIS-R) in a primary care clinic in Santiago, Chile. A Relative Operating Characteristic (ROC) analysis was used to determine the optimal threshold point for case definition and to compare the performance of these two questionnaires. The validation coefficients for the GHQ-12 and the SRQ 20 were, respectively: sensitivity 76% and 74%; specificity 73% and 77%; overall misclassification rate: 26% and 25%. Misclassification by these questionnaires was significantly associated with education and sex, males being more likely than females to be misclassified as false negatives and poorly educated respondents as false positives. The symptom response profile of both questionnaires showed that the most prevalent items were psychological complaints of anxiety and depression. Both instruments seem to have a similar ability to identify minor psychiatric disorders in primary care in Chile. PMID- 1411745 TI - Expressed emotion, relapse rate and utilization of psychiatric inpatient care in schizophrenia. A study from Czechoslovakia. AB - The link between expressed emotion (EE), relapse rate and the length of rehospitalization in the 12 months after index discharge was investigated in a sample of 125 patients with a diagnosis of schizophrenia or schizoaffective psychosis. The results showed that EE was the best single predictor of relapse and that patients from high EE families spent three times as long in hospital as patients from low EE families. The protective impact of regular antipsychotic medication and low face-to-face contact with relatives was found in patients both from high and low EE families. PMID- 1411746 TI - Evaluating the diagnostic criteria for panic disorder: measures of social morbidity as criteria. AB - Over 9% of the subjects in the NIMH Epidemiologic Catchment Area sample reported a history of at least one panic attack, yet only 1.5% of the sample met DSM-III criteria for panic disorder. In light of the revisions of these criteria for DSM IV, two of those diagnostic criteria, frequency of panic attacks and number of symptoms during a panic attack, are examined in this paper. We evaluated the relationship between those criteria and each of three measures of social morbidity:psychiatric hospitalization, emergency room (ER) use for emotional problems, and suicide attempts. Although only symptom count was significantly associated with either ER use or suicide attempts, both diagnostic criteria were associated with psychiatric hospitalization. The threshold for symptom count was also considered and while three appeared to have slightly better sensitivity and specificity, the continued use of four symptoms seemed acceptable. The diagnostic and clinical implications of the findings are considered. PMID- 1411747 TI - Why discrepancies exist between structured diagnostic interviews and clinicians' diagnoses. AB - The authors employed empirical methods to study the causes of discrepancies between clinicians' and epidemiologists' diagnoses of "cases" from the general population within the homogeneous DSM-III/DIS system. Four interviewers conducted 139 interviews using the DIS, while psychiatrists completed a DSM-III checklist, after which they could then ask any questions they wanted. All kappas exceeded 0.58. Meetings were subsequently organized with all participating psychiatrists in order to point out reasons for discrepancies between DIS diagnoses and clinical judgement. The authors came to the following conclusions: (1) DSM-III ambiguities led to discrepancies, especially when reference periods were not specified. (2) Discrepancies arose when cases were difficult: symptoms pertaining to different diagnoses or multiple diagnoses and the fact that clinicians could use volunteered comments, while interviewers were obliged to keep strictly to the schedule, contributed to discrepancies. (3) Other approaches, such as CIDI for anxiety and DISSA for depression, could improve DIS performances. PMID- 1411748 TI - Outcome of discharged psychiatric patients after short inpatient treatment: an Italian collaborative study. AB - This paper presents the results of an Italian multicentre study on the 6-month outcome of psychiatric patients discharged after short-term in-patient treatment from 21 general hospital psychiatric units. Two outcome measures were used: relapses (defined as readmissions for psychiatric treatment or suicide) and community tenure. The data showed, on average, a fairly high relapse rate (43% in 6 months) combined with a good community tenure. The findings are discussed in the light of the heterogeneity in patterns of care provision observed in Italian psychiatric services after the changes introduced by the 1978 Mental Health Act, reported in a previous paper. PMID- 1411749 TI - Prevalence and demographic correlates of alcohol-related problems in Japanese employees. AB - To examine the relationship of basic sociodemographic characteristics to alcohol related problem in Japanese employees, a questionnaire survey was conducted of a total of 2,581 employees of a computer factory in a suburb of Tokyo. The questionnaires included items on gender, age, marital status, social class (i.e., education, family income and occupation), alcohol consumption, and the Kurihama Alcoholism Screening Test (KAST). Data from 1098 male and 265 female current drinkers aged 20 years or older were analyzed; 15% and 6% of the male and female subjects, respectively, were classified as having alcohol-related problems on the basis of the KAST score (13% and 4% of the entire study population, respectively). Multiple logistic regression analysis indicated that alcohol related problems were more prevalent in the less educated, managers and those who had a high alcohol consumption. The results suggested that education and occupation are important factors related to alcohol-related problems in Japanese employees. PMID- 1411751 TI - Vertebral burst fractures: an experimental, morphologic, and radiographic study. AB - Spinal burst fractures are produced by rapid compressive loading, and may result in spinal cord injury from bone fragments forced from the vertebral body into the spinal canal. This fracture is one of the most difficult injuries of the spine to successfully treat, in part because the biomechanics of reduction and the exact mechanism by which the distraction forces are transmitted to the intracanal fragments of the burst fracture have not been adequately investigated. The authors developed a reproducible technique for creating these fractures in vitro. The fractures produced were identical to those observed in clinical practice, and were used for investigating the mechanics of this fracture and its reduction. This work describes the pathologic anatomy of the burst fracture both on the gross structure and also on microtome sections of the vertebrae, and examines the biomechanics of fracture reduction. The margins of the vertebral bone fragment, which was forced posteriorly into the spinal canal during fracture, were noted to extend far laterally beyond the pedicles. The authors also found extensive damage not only to the disc above the injured level, but also to that below, explaining the clinical observation that disc degeneration frequently occurs at both levels. Examination of anatomic data provided by microtome section supported the hypothesis that the fibers that actually reduce the intracanal fragment originate in the anulus of the superior vertebra in the midportion of the endplate and insert into the lateral margins of the intracanal fragment. Investigations using magnetic resonance imaging confirmed that these obliquely directed fibers account for the indirect reduction of the fragment. The authors' studies demonstrate that the posterior longitudinal ligament provides only a minor contribution in the reduction of the fracture in comparison to the attachments of the posterior portion of the anulus fibrosus. The forces required to reduce this fragment were studied. Distraction was found to be the predominant force required for indirect posterior reduction. This was confirmed by a series of tests using devices that provided segmental fixation. The application of uniform distraction forces was most effective in the posterior reduction of the intracanal fragment. PMID- 1411750 TI - Prevalence of infantile autism in four French regions. AB - A survey conducted in four French regions identified a sample of 154 autistic children born in the birth cohorts 1972 and 1976. Their mean ages were respectively 6.9 and 5.5 years when their handicaps were registered to local administrative services. The overall prevalence estimate is 4.9/10,000, with little difference between the two cohorts. The boy/girl sex ratio is 2.1:1, and more than two thirds are mentally retarded. The SES distribution does not deviate from census data. An elevated incidence of epilepsy is found (22%), with higher rates among the most retarded subjects and those with perinatal antecedents. Otherwise, relatively few autistic subjects were reported to have a clearcut medical disorder known for its association with autism. PMID- 1411752 TI - Fibrinolytic activity as a predictor of the outcome of prolapsed intervertebral lumbar disc surgery with reference to background variables: results of a prospective cohort study. AB - In a prospective study 122 patients with a slipped lumbar disc and no previous surgery were preoperatively examined for fibrinolytic activity. Surgical results for these patients were evaluated 12 months postoperatively by clinical overall assessment. In a multiple linear regression analysis fibrinolytic variables, euglobulin clot lysis time and plasminogen activator inhibitor 1, were shown to have predictive value regarding outcome of surgery; that is, normal fibrinolytic activity favors a satisfactory outcome and vice versa. Background variables and lipid profile were also recorded preoperatively. Body mass index, gamma-glutamyl transpeptidase, triglycerides and smoking were of statistical significance in relation to euglobulin clot lysis time and plasminogen activator inhibitor 1. Postoperative fibrinolytic re-examination of 20 patients seem to confirm that patients at risk of surgical failure have a prolonged depression of fibrinolytic activity. PMID- 1411753 TI - Classification of nonspecific low back pain. I. Psychological involvement in low back pain. A clinical, descriptive approach. AB - An unselected sample of outpatient subjects (n = 330) with localized nonspecific low back pain (LBP) was studied. Investigation consisted of clinical assessment, physical examination, and psychiatric interview based on the DSM-III classification. A psychiatric disorder, according to the DSM-III criteria (axis I) was found in 41% of the subjects. Multiple correspondence analysis and cluster analysis were used to objectively identify clinical subtypes without preconceived theoretical models. Correspondence analyses suggested the existence of a 'psychological pain' syndrome consisting of several of the following symptoms: diffuse back pain, impossibility to assess intensity of pain on a pain scale, aggravation of pain by changing climate, by domestic activities or by psychological factors and dysesthesias in the back. Cluster analysis provided support for a four-group classification of low back pain, which may be interpreted through the relationships between psychological disturbances and the LBP clinical features. The results call for further investigation of the complex relationship between psychological disturbances and back pain. However, clinicians must be aware of the interest of a minimal psychiatric assessment in low back pain patients: psychiatric disorders frequently appear in these patients and an appropriate treatment of the psychiatric syndrome may reduce back pain. PMID- 1411754 TI - Classification of nonspecific low back pain. II. Clinical diversity of organic forms. AB - A classification study was conducted in an unselected sample of outpatient subjects with localized nonspecific low back pain. The heterogeneity of a subgroup of patients without a psychiatric disorder according to the DSM-III classification (axis I), and whose low back pain may be labeled as 'purely organic' (see part 1 of the study in the companion paper), led to further evaluation of this group by correspondence and cluster analysis. A seven-cluster population structure emerged from the cluster analysis. Comprehensive description of these clusters suggests at least four well-differentiated clinical entities or 'syndromes.' Although no satisfactory correlation with pre-existing 'pathoanatomic' classification or hypotheses was found, this variable clinical presentation suggests different etiological or physiopathologic patterns for low back pain (and possibly more specific management of this condition). More comprehensive descriptions and evaluations of clinical symptoms and syndromes appear necessary in order to elaborate a clinical classification of LBP. PMID- 1411755 TI - The evolution of compensated occupational spinal injuries. A three-year follow-up study. AB - This study was undertaken to follow up an incidence rate study of spinal injuries carried out from a cross-sectional random sample consisting of 2,342 workers who were compensated at least once in the year 1981 by the Quebec Worker's Compensation Board (QWCB) for an absence from work. These workers were followed for 3 years using the QWCB information system to record any recurrence of compensated absence from work. A total of 850 (36.3%) had at least one recurrence, and had longer episodes of absence than those without a recurrence (P less than 0.0001). Of these 850 workers, 824 (96.9%) had less than five recurrences and showed a systematic trend of gradual increasing duration of absence on each subsequent recurrence (P less than 0.05 in a repeated measures analysis of variance). A positive relationship was found between the duration of the initial episode of absence from work and the subsequent history of absence from work, both in terms of risk of recurrence (P less than 0.001) and of cumulated absence from work (P less than 0.0001), after controlling for age, sex, and site of symptoms. The computed instantaneous risk of entering a recurrence in a 31 year-old man experiencing lumbar symptoms, was 19.9% (95% confidence interval = 19.8-19.9) in the year following an initial episode of one day duration, and 26.7% (95% confidence interval = 24.3-29.3) after an initial episode of 6 months. PMID- 1411756 TI - Self-reported low back symptoms in urban bus drivers exposed to whole-body vibration. AB - The prevalence of self-reported low back symptoms was investigated by a postal questionnaire in a group of 234 urban bus drivers exposed to whole-body vibration and postural stress and in a control group of 125 maintenance workers employed at the same bus municipal company. The average vertical whole-body vibration magnitude measured on the seat pan of the buses was 0.4 m/s2. After controlling for potential confounders, the prevalence odds ratios for the bus drivers compared to the controls significantly exceeded 1 for several types of low back symptoms (leg pain, acute low back pain, low back pain). The occurrence of low back symptoms increased with increasing whole-body vibration exposure expressed in terms of total (lifetime) vibration dose (years m2/s4), equivalent vibration magnitude (m/s2), and duration of exposure (years of service). The highest prevalence of disc protrusion was found among the bus drivers with more severe whole-body vibration exposure. Frequent awkward postures at work were also related to some types of low back symptoms. It is concluded that bus driving is associated with an increased risk for low back troubles. This excess risk may be due to both whole-body vibration exposure and prolonged sitting in a constrained posture. The findings of this study also indicated that among the bus drivers low back symptoms occurred at whole-body vibration exposure levels that were lower than the health-based exposure limits proposed by the International Standard ISO 2631/1. PMID- 1411757 TI - The association of pain with physical activities in chronic low back pain. AB - Most patients with chronic low back pain associate strenuous physical activities with increased pain. This association can cause avoidance of those activities believed to cause intolerable discomfort. This study explored the relationship of performance of physical activities with self-reported pain measures in 40 consecutive patients with disabling low back pain (mean duration 17 months) during a functional restoration rehabilitation program (mean treatment period 7 weeks). Evaluations were performed at initial presentation and at program completion. Measures included quantification of performance on eight physical tests assessing flexibility, lifting capacity and endurance. Before physical testing patients were asked to complete a pain analog scale, a quantified pain drawing, and a rating of the pain anticipated to result from the performance of each physical test. Results showed that pain measures did not generally correlate with measured physical performance. At completion of treatment, significant improvement in performance on all physical tests was found, but these were not associated with consistent changes in pain measures. These results demonstrate that subjects with chronic low back pain can increase their physical performance abilities within their same pain experiences. Medical recommendations for subjects' involvement in physical activities should not be based solely on the reported association of pain with those activities. PMID- 1411758 TI - Lifting capacity. Indices of subject effort. AB - The association between manual materials handling and occupational low back injuries has generated a wide variety of devices and protocols for testing lifting capacity. The validity of these tests depends critically on the subject's effort during the evaluation. This study compares the accuracy of several physiologic effort indices in identifying maximal and submaximal lifting efforts. Twenty-one men and twenty-three women free from back pain underwent isometric, isokinetic, and isoinertial tests of lifting capacity applying 50 and 100% efforts in random order. Effort indices included isokinetic force/distance curve variation, isoinertial peak force: weight ratios and peak force--weight differences, and heart rates and peak force variances for all three modes. Differences between 50 and 100% effort means were significant at P less than 0.01 for isokinetic force/distance curve variation, isoinertial peak force: weight ratios, and peak force--weight differences, and for heart rates in all three modes using analysis of variance. Differences were not significant (P greater than 0.05) for peak force variances in any mode using Wilcoxon Signed Rank Tests. According to a discriminant analysis model with optimal cutoff values, the only effort indices with better than 60% accuracy in identifying maximal and submaximal efforts were isokinetic force/distance curve variation (74%) and isoinertial peak force: weight ratios (69%), peak force--weight differences (62%) and heart rates (65%). For each index, subjects were divided into three groups according to whether their lifting outputs during 50% effort bouts were greater than, equal to, or less than one half their outputs in the 100% effort bouts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411759 TI - Computed tomographic follow-up study of forty-eight cases of nonoperatively treated lumbar intervertebral disc herniation. AB - The authors prospectively followed the natural evolution of lumbar disc herniation in 48 patients treated by conservative measures. The initial computed tomographic scan was obtained during the acute phase of the disc herniation and the second was performed 1-48 months after healing. The initial computed tomographic scan allowed classification of the herniations according to size: 13 were considered small, 20 medium and 15 large. Comparison with follow-up computed tomographic scans showed that 9 of the herniations decreased by at least 25%, 8 decreased between 50 and 75% and 31 decreased between 75 and 100%. In the later group, a few had disappeared even though the second computed tomographic scan was performed as early as the month immediately after successful treatment. The largest herniations were those which had the greatest tendency to decrease in size. It is postulated that this could be secondary to the herniation breaking through the outer fibers of the anulus and entering the epidural space. PMID- 1411760 TI - Local electrophysiologic stimulation in experimental double level cauda equina compression. AB - Double level compression of nerve roots has been known to exist for a long time, but only in recent years the clinical significance of such conditions has been discussed. In the current study, nerve root function in double level compression was analyzed by measurements of tail muscle electromyogram, after stimulations of 1) the intermediate segment between the compression sites and 2) cranial to the two compression sites in a pig model. The electromyogram-amplitudes were more reduced after intermediate, than cranial stimulation. This difference was suggested to be based on an additional increasing threshold to elicit an action potential within the intermediate segment due to a nutritional deficit at this location. The results further stress the importance of local changes within the intermediate segment in double level nerve root compression. PMID- 1411761 TI - The effect of lactate and pH on proteoglycan and protein synthesis rates in the intervertebral disc. AB - The intervertebral disc is the largest avascular tissue in the body. Its metabolism is mainly anaerobic, and thus lactate is produced at a significant rate. As a result the lactate concentrations in the center of the disc may be 8 10 times as high as in the plasma. The pH in the disc center is thus acidic. Because low values of pH are known to affect proteoglycan synthesis in other cartilages, the authors measured the effect of lactate levels and pH on 35S sulphate and 3H-proline incorporation rates in the nucleus of bovine coccygeal discs and in human disc obtained during percutaneous nucleotomy. The maximum incorporation rate occurred at pH 7.2-pH 6.9. Here the rate was 40-50% greater than at pH 7.4. Below pH 6.8 the rate fell steeply, more so for sulphate than for proline. At pH 6.3 the sulphate incorporation rate was around 20 percent that at pH 7.4. The results indicate that proteoglycan synthesis rates in particular are sensitive to extracellular pH, and that the peak rate occurs around the level of pH seen in vivo. Factors that cause lactate levels to rise, such as a fall in O2 levels as the result of smoking or vibration (Holm and Nachemson, 1988) could lead to a fall in proteoglycan synthesis rates, ultimately leading to a fall in proteoglycan content and to disc degeneration. PMID- 1411762 TI - The mechanism of initial flexion-distraction injury in the lumbar spine. AB - The threshold for flexion-distraction injuries was determined on lumbar functional spinal units exposed to a combined flexion-shear load in the sagittal plane. The specimens could resist a bending moment of 121 Nm and a shear force of 486 N at the first sign of a permanent deformation of the osteoligamentous components, which occurred at 78% of the assumed ultimate strength of each specimen. The flexion angulation was 16 degrees. The bone mineral content determined in adjacent vertebrae by means of dual photon absorptiometry was an accurate predictor of structural properties of the entire functional spinal unit even at the first sign of a substantial structural injury and not only at ultimate failure as previously demonstrated. PMID- 1411763 TI - Long-term follow-up of patients with untreated scoliosis. A study of mortality, causes of death, and symptoms. AB - The mortality and causes of death in 115 patients (80 women), born 1902-1937, with untreated scoliosis were compared to the expected according to official Swedish statistics. Subgrouping for cause and onset of scoliosis was done. Fifty five patients had died; 21 of respiratory failure and 17 of cardiovascular diseases. The mortality was significantly (P less than 0.001) increased. The increased risk was apparent at 40-50 years of age. The mortality was significantly increased in infantile (P less than 0.001) and juvenile (P less than 0.01) scoliosis but not in adolescent scoliosis. The mortality was also increased in post-polio scoliosis, scoliosis combined with rickets and scoliosis of unknown etiology indicating an increased mortality in idiopathic scoliosis. Among the surviving patients anti-hypertensive treatment was frequent (23 of 50). PMID- 1411764 TI - Prevalence of scoliosis in children with myelomeningocele in western Sweden. AB - In a cross-sectional study of the prevalence of scoliosis in patients with myelomeningocele, 131 patients 5-20 years of age were investigated with clinical examination and radiograms. Sixty-nine percent of the myelomeningocele patients had scoliosis, this prevalence being present already at a young age (6 years). The occurrence of scoliosis increased drastically at high levels of dysraphism, being 20% in patients with sacral myelomeningocele but 94% in patients with thoracic MMC level. Between ages 5 and 10, the mean scoliosis increased successively from 15 to 33 degrees. After this age there was no significant further increase. The ambulatory status of the patients was strongly correlated to the scoliosis incidence. Forty-nine percent of the patients had a uni- or bilateral hip dislocation. There was no correlation between the side of the scoliosis convexity and the side of hip dislocation. PMID- 1411765 TI - Sitting balance in spinal deformity. AB - A computerized pressure plate system was used to analyze the sitting pressure distribution and balance of 100 subjects with both normal and abnormal spines. Normal subjects had a balanced sitting posture with the weight taken evenly on each ischial tuberosity. Patients with idiopathic scoliosis showed significant sitting imbalance especially in the presence of lumbar curves. Bracing improved the sitting balance and stability in most patients. Abnormal sitting patterns were seen with the spinal deformities of myelodysplasia or cerebral palsy. Some patients with severe scoliosis had very asymmetric patterns, which correlated with their loss of sitting stability. The kyphosis of myelodysplasia produced an abnormal tripod sitting pattern due to pelvic flexion and a hyperlordosis of cerebral palsy a pubic sitting pattern due to pelvic extension. The patients studied after spinal fusion also had poor sitting balance and occasionally persisting decubitus ulceration. PMID- 1411766 TI - Delay in diagnosis of intradural spinal tumors. AB - Fifty-seven patients with primary intradural spinal tumors operated on in North Manchester and Salford between 1978 and 1988 were reviewed retrospectively. The commonest diagnoses were meningioma and nerve sheath cell tumors (neurilemmomas and neurofibromas). The median delay in diagnosis was 2.5 years (range 3 days to 24 years). Fifty-eight percent were initially referred to orthopaedic surgeons and 95% percent to specialties other than neurosurgery. The commonest presenting symptom was back pain, but later neurologic and urinary symptoms came to predominate. Eighty-eight percent are disease-free at a mean follow-up of 5.7 years. Symptoms were partially or completely relieved in the majority of patients. Delay in diagnosis of these tumors arises from failure to consider the diagnosis in patients with longstanding back pain or neurologic problems. PMID- 1411767 TI - Effect of straight leg raising on blood pressure. PMID- 1411768 TI - Fracture of the occipital condyle. Case report. PMID- 1411769 TI - Vertebral and hip movement occurs almost simultaneously during symmetric bimanual lifting movements. PMID- 1411770 TI - [Public administration in health: a challenge of our times]. PMID- 1411771 TI - [Financial diversity for the delivery of health services]. AB - Financial options for the National Health System in Mexico are discussed in this paper. In the first part the conceptual elements needed to support financing schemes are presented. The second part deals with financing models of the National Health System. Finally, a map of financing proposals are discussed with the aim of enriching the financial options of the health sector. PMID- 1411772 TI - [Decentralization of the health sector in Mexico. Scope and limitations of local health systems]. AB - This paper is a product of the reflection on the decentralization and sectorization experiences in Mexico since 1917 with particular emphasis on the 1980s. The historical analysis included the creation of an analytical model designed to identify the relationship between the distinct sanitary policies implemented in Mexico and the tendencies towards decentralization and integration. This analysis is combined with a critical review of the recent decentralization experiences undertaken in the states of Guerrero, Oaxaca and Nuevo Leon. While comparing Guerrero and Oaxaca, restitution and deconcentration under similar socio-economic conditions were discussed. The comparison between Guerrero and Nuevo Leon allowed the discussion of the benefits and limits of restitution under different socio-economic conditions. In addition, with this model the author discusses a few generalizations regarding the possible future of decentralization. PMID- 1411773 TI - [Regionalization]. AB - Health services regionalization is analyzed in its concept, components, characteristics and variations through literature review of experiences in different countries. It is concluded that regionalization means ordering or reordering resources and services within an area, provided that physical installations and personnel are already organized in order to assure health services at the highest quality. Those services must be economical, accesible and established in a comprehensive, coherent set with different levels of care in order to meet patients' needs. A regionalization model based on silos is presented, including functions, strategies and policies. Reasons to encourage the regionalization are also presented, such as the decrease in costs, increasing of program effectiveness and the potential development of the regionalized areas. PMID- 1411774 TI - [Health technology in Mexico]. AB - The features of the health technology cycle are presented, and the effects of the demographic, epidemiologic and economic transition on the health technology demand in Mexico are discussed. The main problems of science and technology in the context of a decreasing scientific and technological activity due to the economic crisis and the adjustment policies are also analyzed: administrative and planning problems, low impact of scientific production, limitations of the Mexican private sector, and the obstacles for technology assessment. Finally, this paper also discusses the main support strategies for science and technology implemented by the Mexican government during the 1980s and the challenges and opportunities that lie ahead. PMID- 1411775 TI - [Advances and challenges in setting priorities in health]. AB - The advances and problems in the definition of explicit criteria to measure health needs are discussed. In part one the advantages and limitations of the retrospective and prospective approaches in the identification of health needs for a rational distribution of resources are described. In part two progress in the application of explicit criteria for the prioritization of diseases and interventions to control them are analyzed. Finally, the methodological, conceptual, and operative challenges confronted by this field are discussed. PMID- 1411776 TI - [Coverage of health services]. AB - In this paper the concepts and criteria related to health coverage are discussed in the context of the organization of national health systems. The main international agreements based on WHO/PAHO proposals are also described. The relationship between primary health care and health coverage is analyzed and the evolution of the programs for the extension of health coverage in Mexico are discussed, with emphasis on the problems of overlap and definition of the universe in the several institutions of the health sector. Finally, the author reviews the problems to measure coverage in order to guarantee social and operative efficiency of the Mexican health system. PMID- 1411777 TI - [From analysis to action: various conclusions of the forum]. PMID- 1411778 TI - [Towards a strategy of quality assurance. From concepts to action]. AB - The purpose of this paper is to present the basic principles needed to implement a national strategy for quality assurance in medical care in Mexico. The first part is devoted to a review of the basic concepts of quality of care with the aim of analyzing the evolution of the discussion of the concept of "quality assurance". This review constitutes the reference frame of the description of the historical evolution of quality assurance in different parts of the world. Finally, the experiences regarding quality assurance in Mexico are discussed and several basic proposals for the design of a national quality assurance strategy are presented. PMID- 1411779 TI - [Efficiency in the delivery of health care]. AB - In this paper the role of efficiency in health care delivery is discussed. In the first part several definitions of efficiency are presented and the most common efficiency analysis are described. In the second part of the paper some experiences aimed at improving the efficiency of health care delivery in England, Latin America and Mexico are discussed. Finally, the author presents four proposals for the improvement of efficiency of health care delivery in Mexico: monetary reward associated to performance, alternative organization of health services, investment in management training for health manpower, and operational research in the health systems. PMID- 1411780 TI - [Is survival enough? Challenges of the integration of health and well-being in the third world]. AB - In this paper the paths taken by developing countries to improve the health and well-being of their populations in a context of diminishing resources is discussed. Emphasis is placed on Latin American countries and the objective is to clarify the changing nature of the relationship between health and social well being in the 1970s and 1980s. In the second part of the paper three viable and different political scenarios to confront this problem are presented: 1) survival without well-being; 2) survival and eradication of extreme poverty, and 3) survival, eradication of extreme poverty, and selective reconversion of the poor. PMID- 1411781 TI - [Co-responsibility and social participation]. AB - Social participation in health is the main issue of this paper. In the first part the role of the state and the necessary elements to guarantee political stability are discussed. In the second part the various forms of social participation are described. Finally, two possible scenarios regarding participation of the society in health activities in Mexico are analyzed. PMID- 1411782 TI - [Integration of the delivery of health services]. AB - In Mexico the Constitution defines the right to health care as a social right and, as such, confers to the state the guiding role in the access of the population to health services. Unfortunately, this constitutional principle has not been fully met. One of the reasons for this is the fragmentation of public action in health and the continuous postponement of the integration of health services. In this paper the conceptual and practical limits of integration of health services are discussed, using as starting point a brief diagnosis of inequity and fragmentation of the health system in Mexico. The doctrinaire principles of integration are also described, as well as its practical advantages and disadvantages. Finally, a typology of forms of integration and previous integration experiences in Mexico are discussed. In the concluding remarks the integration prospects for Mexico are analyzed. PMID- 1411783 TI - [Equity and health]. AB - This paper discusses the right to health in Mexico. The authors present some ideas regarding equity and data which shows the existence of a deep inequity in the field of health in the country. The efforts of the social security agencies and of the Ministry of Health aimed at diminishing inequity in health are also described. The authors conclude that it is time to avoid retorical positions and attitudes of administrative solidarity and start to implement actions to improve the health conditions of those living in extreme poverty. These actions should include providing comprehensive health services to all the population, reinforcing specific preventive programs, improving certain basic health indicators and prompting intersectoral collaboration. PMID- 1411784 TI - [X-ray study of the upper gastrointestinal tract. 1. The esophagus]. PMID- 1411785 TI - [Visible mammographic changes following breast-conserving therapy: radiation effects or recurrence?]. PMID- 1411786 TI - [Ultrasonic study of the breast]. PMID- 1411787 TI - [Computed tomography of the paranasal sinuses in coronal section--a prerequisite for endonasal surgery]. PMID- 1411788 TI - [Trends in medical radiation physics. Outlook for radiation oncology]. PMID- 1411789 TI - [Rehabilitation of RA]. PMID- 1411790 TI - [Clinical significance of rheumatoid factor--its complement activating property and isotype]. AB - We investigated the relationship between complement-activating properties of rheumatoid factors (RF) and their isotypes. Active and inactive RA patients without extra-articular symptoms (EAS) and those with EAS were studied. Patients with SLE, liver cirrhosis (LC) and normal volunteers were served as controls. Isotype of RF was measured by ELISA and complement activation (CA) of RF was measured by hemolytic assay. The CA values were significantly higher in RA patients with EAS than those in RA patients without EAS and with other diseases. The IgG and IgM-RF values were significantly higher in active RA without EAS than in inactive RA. Positive correlations between IgM-RF values and CA values were observed in RA with or without EAS, SLE and LC. The Sephadex G-200 gel filtration analysis of sera revealed CA in only 19S IgM fraction. Additionally, we purified 19S IgM-RF from sera of RA, SLE and LC patients by affinity chromatography, and found 19S IgM-RF had CA. These data suggest that serum IgM-RF may play a critical role in the pathogenesis of RA, especially in RA with EAS. PMID- 1411791 TI - [Studies on criteria for clinicopathological diagnosis of allergic granulomatous angiitis (AGA)]. AB - Comparative studies in the evaluation of criteria for clinicopathological diagnosis of AGA which was proposed by Japanese Health and Welfare Ministry (JHWM) in 1988 and American College of Rheumatology (ACR) in 1990 were conducted. Twenty seven Japanese patients with AGA and 231 Japanese controlled patients with polyarteritis nodosa (PAN) and Wegener's granulomatosis (WG) were used as material patients who had been provided a second questionnaire in 1984 sponsored by the JHWM. As a result, the JHWM criteria was 85.2% in sensitivity and 96.5% in specificity, which was superior to the ACR criteria being 74.1% in sensitivity and 93.9% in specificity. These results were due to the low sensitivity and low accuracy in paranasal sinus abnormality and pulmonary infiltrates which were included in the ACR criteria. Furthermore, the JHWM criteria could be diagnosed as AGA using not only the histopathological findings but by the clinical symptoms alone. The controlled patients who were overdiagnosed as AGA using ACR criteria were thought to be included as patients with WG. On the other hand, the controlled patients who were overdiagnosed as AGA using JHWM criteria were thought to be included as patients with overlap syndrome of AGA and PAN. Accuracy of polyneuropathy, muscle weakness, melena and pretibial edema were over 60%, indicating that these clinical symptoms were available for vasculitis symptoms of the JHWM criteria. PMID- 1411792 TI - [Induction of interleukin-1 production in the cultured synovial cells from patients with rheumatoid arthritis]. AB - Interleukin-1 (IL-1) is believed to be involved in articular destruction in rheumatoid arthritis. HLA-class II antigens are expressed on synovial cells of patients with RA. The relation between the production of IL-1 and expression of HLA-class II antigens was studied. Synovial cells of rheumatoid patients appeared to express HLA-DR and DQ antigens to a significantly greater extent than those of osteoarthritic patients. These cells produced IL-1 following interferon-gamma (IFN-gamma) stimulation and there was synergistic enhancement of production induced by IFN-gamma and monoclonal antibodies to HLA-DR or DQ antigens in combination. In the intracellular signal transduction mechanism for the production of IL-1 beta by these cells following IFN-gamma stimulation, protein kinase C and calmodulin may be involved as second messengers. PMID- 1411793 TI - [A histological study on the synovial tissue of rat knee joints in the experimental beta 2-microglobulin derived amyloidosis]. AB - In recent years, a clinical syndrome comprising carpal tunnel syndrome, destructive spondylarthropathy, and cystic bone lesions has been recognized in the long-term hemodialysis patients. It is well known that the amyloid deposits have been found in these affected tissues and also beta 2-microglobulin (beta 2 MG) has been identified as an amyloidgenic protein. But, those problems such as the mechanisms of amyloidgenesis from beta 2-MG in vivo and the subchondral bone cysts formation are not clarified yet. If it becomes clear, it will give us a very useful information of therapeutic and prophylactic considerations to the hemodialysis related arthropathy. Since the experimental amyloidosis derived from beta 2-MG has not been reported in the past, we intended to make the experimental amyloidosis derived from beta 2-MG in rats. We have used the Sprague-Dawley strain rats (4 weeks old) and performed the 3 different procedures as follows. Procedure 1: clip renal vessels to make the experimental renal failure. Procedure 2: induce arthritis by the type II collagen induced arthritis (CIA). Procedure 3: inject beta 2-MG (10 micrograms) into the knee joint once every week for 6 weeks. We combined the above-mentioned procedures to make 5 experimental groups as follows. Group A: Procedure 1 + Procedure 3. Group B: Procedure 1 + Procedure 2. Group C: Procedure 1 + Procedure 2 + Procedure 3. Group D: Procedure 2 + Procedure 3. Group E: No treatment. After 6 weeks, they were sacrificed. We took specimens from the synovium and bone in their knee joints. First, the light microscopic specimens are stained with the Congo-red stain. When we confirmed the positive green birefringence in polarized light, we have performed the immunohistochemical stain with the monoclonal anti-amyloid P-component antibody, the anti-beta 2-MG antibody and the anti-amyloid A protein for the immunohistochemical stain subsequently. Moreover, we have used the electron microscope to confirm the amyloidfibrils in cases that the Congo-red and immunohistochemical stain of the amyloid P-component are both positive. As a result, we could confirm the amyloid fibrils in the 60% of the group C only. In this group, the amyloid deposition is observed in the inflammatory proliferated synovium in the joint as well as the subchondral bone lesion where the synovial capsule attaches to the bone. In other groups, although a certain degree of inflammation or proliferation of synovium as well as erosive changes of the joint surface are found, no amyloid deposition is confirmed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1411794 TI - [A case of the eosinophilia-myalgia syndrome]. AB - The Eosinophilia-myalgia syndrome (EMS) is a recently described clinical entity consisting of severe myalgia and eosinophilia that has ascribed to the ingestion of the amino acid L-tryptophan. Over 1500 cases of EMS have been reported to the Centers for Disease Control of United States as of June 1990. We report a case of EMS associated with the ingestion of L-tryptophan. A 24-year-old woman was admitted to our hospital due to severe myalgia. She had swelling on extremities and eosinophilia (1880/mm3). Full thickness biopsy of affected portion showed inflammation of fascia with eosinophils and histiocytes, which were compatible with eosinophilic fasciitis. She had a history of ingestion of fitness protein tablets bought at Hawaii for 3 months from Sep. to Dec. 1989, which contained the amino acid L-tryptophan. On the basis of these findings, we diagnosed her as EMS. It is suggested that this case is rare and important in Japan. PMID- 1411795 TI - [Lobenzarit disodium (CCA)--induced diabetes insipidus in a patient with rheumatoid arthritis]. AB - A 44-year-old female with 16-year history of rheumatoid arthritis visited Akiru Hospital with complaints of a thirst, a dry mouth and a general fatigue. One week prior to admission, the patient manifested excessive thirsty feeling, a body weight loss and a sleepless by the polyuria. She has been given 5-10 mg of prednisolone and 240 mg of lobenzarit disodium (CCA) in a day for 11 months. A hematologic examination showed no abnormality, and the examination of her serum showed the following values: BUN, 9.3 mg/dl; creatinine, 0.9 mg/dl; sodium, 139 mEq/l; chloride, 102 mEq/l; potassium, 3.9 mEq/l; osmolality, 290 mOsm/l. Plasma antidiuretic hormone (ADH) level increased slightly (6.0 pg/ml). Examination of her urine revealed specific gravity, 1.005; no trace of glucose, protein, blood and ketones; normal sediment; and osmolality, 209 mOsm/l. The patient was given exogenous ADH (10 units of vasopressin tannate in oil, intramuscularly) to obtain a diagnosis, and she was found to be unable to concentrate her urine more than 1.008 in the specific gravity. A water restriction, as a test for diabetes insipidus, also failed to concentrate her urine in the specific gravity and in the osmolality. Together with these findings, the patient was diagnosed to be a diabetes insipidus, and CCA was seemed to account for the disease. This unfavorable effect of CCA appeared to be reversible, since the patient recovered her urinary concentrating ability after the medication of CCA was discontinued. PMID- 1411796 TI - [A case of Sweet's syndrome (acute febrile neutrophilic dermatosis) associated with mixed connective tissue disease]. AB - Sweet's syndrome (acute febrile neutrophilic dermatosis) is an unusual condition characterized by fever, polymorphonuclear neutrophil leukocytosis of the blood, thick painful plaques on the face, neck and limbs, and a dense dermal infiltrate of mature neutrophils seen histologically. Recently, this disease has also been reported in association with various malignant neoplasms and chronic inflammatory disorders. In the literature, seven cases of Sweet's syndrome associated with collagen diseases have been reported, but no cases with mixed connective tissue disease (MCTD). The first case of Sweet's syndrome associated with MCTD was herein described and discussed. A 49-year-old man was admitted to our hospital with the complaints of high fever and painful erythema on his face, neck and limbs. Six months ago, MCTD was suspected, with the presence of limited cutaneous sclerosis of the hands, Raynaud's phenomenon, polyarthralgia, an elevation of CPK value and a positive anti-RNP antibody. Just before hospitalization, he suffered a prodromal infection of the upper respiratory tract for two weeks. He was diagnosed as Sweet's syndrome by the clinical and histological features. He began receiving corticosteroid therapy (prednisolone 60 mg/day), and within a week he showed dramatic improvement in the above symptoms. PMID- 1411797 TI - [Improvement of pancytopenia and articular and by splenectomy in a patient with Felty's syndrome]. AB - A forty seven year-old woman with a 18 years history of rheumatoid arthritis presented with recurrent infection and pancytopenia. A diagnosis of Felty's syndrome was made hand on clinical and laboratory findings. In spite of drug therapy using nonsteroidal anti-inflammatory drugs, D-penicillamine and corticosteroid, the hematological abnormalities and active joint symptoms continued. Recurrences of severe bacterial infection and the rupture of esophageal varices necessitated splenectomy. Soon after the operation, dramatic improvement of hematological abnormalities were observed. Furthermore, after 3 months postoperatively, marked decrease in rheumatoid activities and disappearance of subcutaneous nodules were noticed. Titer of rheumatoid factor also showed a significant reduction and became negative 6 months after the operation. Although the efficacy of splenectomy on hematological abnormalities in Felty's syndrome has been well documented, its effect on rheumatic disease has not been clarified. The case presented here might suggested that suppression of reticuloendothelial system may have therapeutic effects in rheumatoid arthritis. The possible mechanisms involved in these findings have been discussed. PMID- 1411798 TI - [Recent progress on rheumatoid factor--idiotype and germline genes]. PMID- 1411799 TI - [Structure and function of nuclear and cytoplasmic protein antigens recognized by autoantibodies]. PMID- 1411800 TI - [Adhesion molecules in the immune system]. PMID- 1411801 TI - Sphenoid sinus disease. Experience at King Edward VIII Hospital, Durban. AB - The increasing use of computed tomography (CT) to evaluate sinus disease in general, appears to have led to an increased pickup rate in isolated sphenoid sinus disease. It is probable that subtle disease of the sphenoid sinus was missed before the use of CT as a diagnostic tool. Six patients with sphenoid sinus disease and related pathological conditions seen during the past 2 years, are reviewed; these included 4 mucoceles, 1 case of aspergillosis and 1 of squamous cell carcinoma. Experience with sphenoid disease, with particular reference to the diagnosis, management and complications of this condition, is discussed. PMID- 1411802 TI - Endoscopic transnasal dacryocystorhinostomy. Results in 21 patients. AB - The transnasal endoscopic approach to the nasolacrimal sac was successfully applied in 20 out of 23 operations. The patients were followed up for 4-26 months, the first 21 operations having been performed in August 1988. Twenty-one nasolacrimal sacs had primary endoscopic transnasal surgery and 2 had previous failed external operations. Five operations were revised of which 3 were still unsuccessful. PMID- 1411803 TI - Massive gastro-intestinal haemorrhage due to vascular ectasia of the duodenum. A case report. AB - Vascular ectasia of the duodenum as an unusual source of upper gastro-intestinal bleeding in a patient with cirrhotic portal hypertension and oesophageal varices is reported. Morphological structure and situation of ectatic duodenal vessels indicate the possible coexistence of variceal distension and angiodysplasia. PMID- 1411804 TI - Is tube cecostomy safe in the surgery of Hirschsprung's disease? AB - The use of concomitant tube cecostomy remains an option for decompression after distal large-bowel surgery but has been criticised because of a reported high complication rate. Two hundred and three patients who underwent a Soave endorectal pull-through procedure for Hirschsprung's disease (1974-1990) were evaluated. Operative technique included a modified sutured Soave endorectal pull through procedure and a Stamm tube cecostomy utilising a large-lumen catheter. One hundred and twenty patients who had a modified two-stage procedure plus concomitant tube cecostomy were compared with 83 patients who underwent a three stage procedure with colostomy cover. Early postoperative complications occurred in 8 patients (6.6%) in whom cecostomies were performed. A distal cuff abscess developed in 1 patient (0.8%), an anastomotic leak in 1 (0.8%) and 3 patients (2.5%) had colo-anal stenosis. The cecostomy tube dislodged in 2 patients and 1 required operative closure of a faecal fistula at the cecostomy site. Colonic venting was adequate and little nursing care was required. In 2 instances colonic distension developed after cecostomy clamping. Decompression was achieved by opening the cecostomy tube; this resulted in relief of symptoms and a good subsequent recovery. In contrast, there were 11 postoperative complications in the 83 patients undergoing a three-stage procedure (13.2%). In 2 patients (2.4%) an anastomotic leak occurred and 5 distal cuff abscesses (6%), 3 (3.6%) early strictures and 1 (1.2%) neorectal retraction developed. The use of a concomitant tube cecostomy with a two-stage Soave procedure is an effective and safe means of providing proximal colonic venting and did not add to mortality or morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411805 TI - The clinical researcher--present and future prospective. PMID- 1411806 TI - Presentations to the Surgical Research Society of Southern Africa--the second 10 years (1982-1991). AB - Over the 10-year period 1982-1991, 594 papers were read at the annual meetings of the Surgical Research Society of Southern Africa. One hundred and thirty-five (23%) reported work performed on experimental animals with a trend to an increase from this base; 152 (26%) were presentations from surgeons-in-training, also with a trend to increase over the decade. The distribution by subspecialty was: upper gastro-intestinal tract 28%; hepatobiliary 12%; vascular 16%; immunology/transplantation 9%; further subspecialties 9%; and miscellaneous 26%. Major observations are that the number of papers has doubled since the first decade, probably due to establishment of the poster session, and that presentations by surgeons-in-training remain in the minority at the Society. PMID- 1411807 TI - Routine peri-operative management of the diabetic patient. AB - Many aspects of peri-operative management of the diabetic patient remain controversial, although there are a variety of approaches towards management. These patients are at risk for certain complications related to the severity and chronicity of the disease. The surgeon and the anaesthetist must be conversant with the management of diabetes in elective and emergency situations. Reasonable metabolic control can be achieved within a few hours pre-operatively and clinical assessment can be performed on an out-patient basis. Anaesthetic management consists of assessment of the control of the disease followed by evaluation of diabetic complications and their severity. Different views are expressed regarding tight control of blood glucose level (4-8 mmol/l) versus moderate control (8-12 mmol/l) when managing diabetic patients. The importance of guarding against factors favouring metabolic decompensation in the peri-operative period, is stressed. Minor or major surgery has important implications regarding the management of diabetes. All patients scheduled for major surgery should be treated with intravenous insulin. Blood sugar should be monitored at regular intervals to protect the patient against hypoglycaemia. Emergency surgery is usually associated with an infectious process. Pronounced hyperglycaemia, dehydration and metabolic derangement may be present. The underlying pathology may aggravate the diabetic state and surgery may actually improve the patient's condition. It is unnecessary to postpone surgery to treat ketosis fully, because this may need 12-24 hours. Extreme insulin resistance and greater insulin requirements are present during cardiopulmonary bypass, hypothermia and rewarming. Beware of severe hypoglycaemia after cardiopulmonary bypass. PMID- 1411808 TI - Diabetic complications with special anaesthetic risk. AB - Diabetes mellitus leads to acute and chronic complications. Acute complications include hypoglycaemia, diabetic keto-acidosis, hyperglycaemic hyperosmolar non ketotic syndrome and lactic acidosis. Chronic complications are neuropathies, nephropathy, retinopathy, peripheral arterial disease, cerebrovascular disease, coronary artery disease, cardiomyopathy, hypertension, infection, delayed wound healing and stiff joint disease. End-organ pathology is in part responsible for the increased morbidity and mortality seen in diabetic patients in the peri operative period. A thorough pre-operative search for end-organ pathology is essential to optimise patient management. Relevant diabetic complications and their anaesthetic risk are discussed. PMID- 1411809 TI - Postoperative hypoxaemia--its causes and prevention. AB - Postoperative hypoxaemia presents with varying degrees of severity. Aetiology of the condition is diverse and may originate in the pre-, intra- or postoperative periods. However, induction of anaesthesia and the type of operation are important initiating factors over which there is little control. The impact of postoperative hypoxaemia, especially when detected early, can be alleviated. This article attempts to explain the pathophysiology and provide suggestions as to detection and management of postoperative hypoxaemia. PMID- 1411810 TI - Pre-operative assessment and management of the patient with ischaemic coronary artery disease in non-cardiac surgery. AB - Peri-operative cardiac events are the leading cause of death following anaesthesia and surgery. We attempt to put into perspective the various methods of pre-operative assessment of patients at risk, and suggest a logical sequence for the use of potentially costly investigations such as 12-lead ECG, exercise stress ECG, ambulatory ECG monitoring, myocardial perfusion imaging, radionuclide ejection fraction, and coronary angiography. Important principles are given for the management of patients at risk of peri-operative cardiac incidents if the decision is made to proceed with non-cardiac surgery despite the potential risk or because of inoperable coronary disease. PMID- 1411811 TI - Management guidelines for hypertension in southern Africa. PMID- 1411812 TI - Violence--today's major public health issue. PMID- 1411813 TI - A policy proposal to manage chronic diseases of lifestyle in South Africa. PMID- 1411814 TI - The future of medical administrators. PMID- 1411815 TI - New emphasis on atrial cardiology. PMID- 1411816 TI - The Columbus quincentenary--500 years of expanding tobacco addiction. PMID- 1411817 TI - The impact of chronic diseases of lifestyle and their major risk factors on mortality in South Africa. AB - The purpose of this study was to determine the impact of chronic diseases of lifestyle on the mortality pattern of South Africans and to estimate the number of South Africans affected by major risk factors for these diseases. The proportion of deaths due to chronic diseases of lifestyle was calculated from the deaths reported to the Central Statistical Services. This group of diseases was responsible for 24.5% of deaths of all South Africans and 28.5% of those aged 35 64 years whose deaths were reported in 1988. The major causes of death contributing to these figures were cerebrovascular diseases (7.2% of all deaths and 7.9% of deaths of persons aged 35-64 years) and ischaemic heart disease (8.7% of all deaths and 9.6% of deaths of persons aged 35-64 years). The age standardised prevalence rates for the major risk factors reported in five cross sectional studies in different areas and groups are compared. Estimates from the reported prevalence rates, based on the size of the South African population recorded in the 1985 census figures, were calculated for the major risk factors. Overall 4.88 million South Africans smoked, the largest group of smokers being black males (2.6 million). for hypertension 5.5 million South Africans had blood pressures above 140/90 mmHg; again the largest groups were blacks (3.0 million). For hypercholesterolaemia and raised low-density lipoprotein cholesterol levels, 4.8 million and 3.1 million South Africans respectively had an increased risk for ischaemic heart disease, blacks having the lowest levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411818 TI - Dietary patterns and nutritional status in free-living older white men with established vascular disease. AB - Thirty-nine white men aged 51-84 years with established vascular disease were studied to investigate the effect of fish oil capsules on the regression of these lesions. This article deals with the baseline data of the study. The subjects completed a 7-day dietary record, weight and height were measured and a fasting blood sample was analysed for proteins, haematological values and certain vitamins. Dietary analysis indicated that the mean energy intake was 8,552 kJ (SD = 2,095). The energy distribution was 15.5% protein, 33.6% fat and 46.4% carbohydrate. In the light of the recommended dietary allowances the diet was lacking in zinc, vitamin B6 and folic acid, which suggests that the subjects might be deficient in these micronutrients. Although the diets were lacking in these nutrients, no clinical stigmata were observed. The subjects averaged a body mass index of 26.1 and could therefore be classified as overweight. The mean haematological values as well as the plasma vitamins were within the normal range. In conclusion it can be said that the men consumed a diet that was too high in fat and that the diet lacked certain micronutrients. PMID- 1411819 TI - The level of mortality in South Africa in 1985--what does it tell us about health? AB - South African mortality data are inadequate for health planning. Estimates of mortality levels in blacks for 1985, derived using indirect demographic techniques, have provided an opportunity to analyse South African mortality in a health context. The infant mortality rate (IMR) for the population as a whole was 64/1,000 live births in 1985, which is high when compared with those of other countries. The IMR varied between population groups and was highest in blacks (males 73, females 68) and lowest in whites (males 11, females 7). Adult mortality rates, measured in terms of the chance of a 15-year-old dying before reaching the age of 60, ranged from 42.8% for black males and 29.4% for black females, to 21.8% and 11.5% for white males and females respectively. Life expectancy at birth of black males and females was 55 and 61 years respectively, while for white males and females it was 68 and 76 years respectively. Infectious diseases are a leading cause of death in blacks under 5 years of age, while trauma, poverty-related diseases and chronic diseases related to lifestyle all contribute to the high levels of adult mortality in this group. Prevention and health promotion strategies focusing on these as well as HIV/AIDS must be incorporated in a primary health care strategy to reduce premature mortality. Most importantly, it is crucial to improve the registration system that is vital to facilitate ongoing evaluation. PMID- 1411820 TI - Beliefs about smoking and health and attitudes toward tobacco control measures. AB - The opinions of a representative sample of adult South Africans about the effects of smoking on health and their attitudes toward tobacco control measures were surveyed by means of an interviewer-administered questionnaire. Seventy-five per cent of the respondents were black and 55.3% were female. More than 50% of blacks and Asians (61.7% and 53.2%) were non-smokers, whereas 52.1% of 'coloureds' were current smokers and 23.8% of whites ex-smokers. The majority of smokers (68.5%) acknowledged the harmful effects of direct smoking and a larger percentage of non and ex-smokers (79.7% and 77% respectively) shared this view. A similar trend was observed in beliefs about passive smoking. Seventy-five per cent of participants felt that tobacco sales to minors should be banned and 55.8% thought that taxes on tobacco products should be increased. There was substantial white opposition to measures that prohibit tobacco companies from sponsoring sporting events. Most respondents felt that tobacco advertising should be banned on television (59.7%), radio (60.1%), in newspapers (58.4%), on billboards (58.7%) and in cinemas (59.3%). The results indicate that in the main the public supports the introduction of the measures proposed in the draft Tobacco Products Control Act and even more extensive legislation to control tobacco consumption. This augurs well for future strategies aimed at tobacco control in South Africa. PMID- 1411821 TI - Alcohol intake in relation to lipids, lipoproteins and blood pressure. AB - A cross-sectional population study of 655 men and 731 women was undertaken to evaluate the association between the level of alcohol intake, the level of high density lipoprotein cholesterol (HDL-C) and its subfractions, and blood pressure in men and women in different age groups (20-44 and 45-64 years). Habitual alcohol intake was significantly related to higher levels of HDL-C in both men and women. In the case of men both HDL2-C and HDL3-C levels were raised, while in women this rise was restricted almost entirely to HDL2-C. Plasma apolipoprotein A I and A-II levels were elevated in men who drank, but not in women. In both, triglyceride and blood pressure levels were raised with habitual alcohol intake, and the increases in HDL subfractions and blood pressure levels became more marked with increasing age in both men and women. Recent alcohol intake had less effect on all the variables except blood pressure. We conclude that both HDL3-C and HDL2-C contribute to the rise in HDL-C levels that accompanies alcohol use, notwithstanding differences in the responses of the sexes. A regular alcohol intake is more likely to be beneficial and some of the positive or protective aspects of alcohol consumption could be reduced by the adverse changes in triglycerides and blood pressure levels. PMID- 1411822 TI - Risk factors and coronary heart disease in Durban blacks--the missing links. AB - Coronary heart disease (CHD) is still relatively uncommon in the black population of South Africa. We embarked on a study to determine the prevalence of risk factors leading to CHD in the black population of Durban. The study sample was selected from patients attending a dental clinic at a hospital. A total of 458 patients (age range 16-69 years) was studied. The prevalence of CHD was 2.4%. The percentage prevalences of selected risk factors were: hypertension (blood pressure > or = 140 mmHg systolic and/or > or = 90 mmHg diastolic) 28% (31.9% for males, 25.4% for females); protective levels of high-density lipoprotein/total cholesterol > or = 20%, 81.3%; diabetes mellitus 4.9% for males, 2.9% for females; smoking > or = 10 cigarettes per day 28.1% for males, 3.4% for females; obesity 3.7% for males 22.6% for females. We found the Minnesota Coding System for electrocardiographic changes of CHD and the Rose questionnaire to be unreliable for eliciting CHD in blacks. Hypercholesterolaemia is less common, and this may explain the low incidence of CHD in blacks. Epidemics of CHD as seen in Indian, coloured and white South Africans can still be prevented in the black population, but preventive measures must be instituted rapidly. PMID- 1411823 TI - Hypertension in family practice. A study of knowledge, attitudes and practices. AB - A study was conducted in Cape Town during 1990 to investigate the knowledge, attitudes and practices of 90 family practitioners with regard to hypertension and its management. Hypertension was regarded as an important health problem by 59% while 5% thought that it was not important. Sixty-eight per cent of family practitioners estimated that less than 15% of their patients suffered from hypertension and 78% of family practitioners estimated that more than 70% of their hypertensive patients' blood pressures were controlled. Fifty-five per cent of family practitioners thought it acceptable for a lay person to measure blood pressure and 68% felt that the use of a hypertension register in the practice would assist in the management of hypertension. The information gathered will be of great value in planning intervention strategies and developing hypertension management aids that could assist the family practitioner. PMID- 1411824 TI - Distribution of health personnel in the Republic of South Africa with special reference to medical practitioners. AB - Data from various sources indicate that there is no shortage of medical practitioners in the RSA. This was confirmed in a 1990 survey by the Department of National Health and Population Development. The perceived shortage is relative in nature and due to a geographical and functional maldistribution. The majority (77%) of medical practitioners reside in metropolitan areas in the RSA; the ratio of doctors to members of the population is 1:696. Only 23% of medical practitioners practise in non-metropolitan areas; the calculated ratio is 1:1 920. The overall ratio in the self-governing territories is 1:15 272 and compares unfavourably with the ratios in non-metropolitan magisterial districts in the RSA. The medical practitioner/population ratio varies fifty-fold between the metropolitan areas in the RSA and the essentially rural self-governing territory of Lebowa (1:30 449). The registered medical practitioner/population ratios for the various development regions vary from 1:672 to 1:7 642. Failure to address these imbalances will have serious implications for the future rendering of acceptable and equitable health care. PMID- 1411825 TI - Can medical graduates afford to become state medical officers? AB - Over the past 7 years, the cost of tuition and residence fees at the University of Cape Town Medical School has risen by 21.75% each year. This is considerably higher than the increase in the consumer price index over the same period and students are increasingly having to resort to loans to finance their education. The starting salary of a medical officer in the state services has, however, only risen by 9.73% each year over the same period. If these trends continue, the likelihood of young medical doctors employed in such posts being able to repay their loans is bleak and the services will experience increasing difficulty in filling posts, particularly in the peri-urban and rural areas. An innovative manner of financing medical education is needed. This could include allowing education costs to be tax-deductible after graduation, or providing incentives, rather than using coercion, to encourage young doctors to settle in less popular locations. PMID- 1411826 TI - The incidence of surgical glove perforation during obstetric and gynaecological surgical procedures. AB - The increasing prevalence of diseases such as AIDS and hepatitis B makes safe surgical techniques more important than ever before. Intact surgical gloves act as a barrier against these infections and a study was therefore done to determine the incidence of surgical glove perforation during obstetric and gynaecological surgical procedures. Surgical gloves were collected and tested for perforations following 353 consecutive obstetric and gynaecological operations. Forty pairs of new unused surgical gloves were tested for perforations in the same way. Whereas none of the 40 control pairs of gloves was found to be perforated, 22%-24% of used gloves were perforated. The experience of the surgeon had no influence on the incidence of glove perforation (P = 0.997; chi 2-test). Left-hand gloves were more frequently perforated than right-hand gloves, but this difference was not statistically significant (P = 0.075: chi 2-test). These findings must be a source of concern to all those practising obstetrics and gynaecology and measures are therefore suggested to decrease the risk of HIV or hepatitis B transmission during operations. PMID- 1411827 TI - Road traffic collisions involving children as pedestrians. Provisional results of a hospital-based study. AB - In December 1990 a study was undertaken at Red Cross Children's Hospital to examine the circumstances surrounding pedestrian injuries in children under the age of 13. The provisional results, based on the first 154 parental interviews, are reported here. There is a strong correlation between pedestrian injury and children playing or running errands in residential areas during day-light hours, particularly in the late afternoon. Lack of adult supervision may be an important factor. The relevance of these findings to future road safety strategies is discussed. PMID- 1411828 TI - Financial compensation following road traffic injury: who is footing the bill? AB - A study was undertaken at Red Cross Children's Hospital to assess how aware parents were of motor vehicle accident (MVA) claim procedures on behalf of their children. Of 160 questionnaires sent out to the parents of road traffic injury (RTI) victims, 100 were answered. Sixty-six per cent of parents who responded had an income below R500 per month. The identity of the motorist responsible for injuring the child was known to only 26 parents. Third party damages were claimed by only 32 parents or guardians; the remaining 68 failed to do so principally through lack of awareness. The implications of these findings for both RTI victims and the hospitals where they are treated are discussed here. PMID- 1411829 TI - The symbol of medicine in ancient China. PMID- 1411831 TI - Discontinuation of bronchographic contrast medium. PMID- 1411830 TI - Further experience with the vaginal strips sling operation. PMID- 1411832 TI - Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. AB - From 1960 10 1984, 2,501 women underwent diagnostic laparoscopy (index laparoscopy) because of a clinical suspicion of acute pelvic inflammatory disease (PID). Of these women, 1,844 had abnormal laparoscopic findings (patients) and 657 had normal findings (control subjects). The reproductive events after index laparoscopy of 1,732 patients and 601 control subjects were followed. The patients and control subjects were followed for a total of 13,400 and 3,958 woman years, respectively. During the follow-up period, 1,309 (75.6%) of the patients and 451 (75.0%) of the control subjects attempted to conceive. Of these women, 209 (16.0%) of the patients and 12 (2.7%) of the control subjects failed to conceive. A total of 141 (10.8%) of the patients and 0 (0%) of the control subjects had confirmed tubal factor infertility, 21 (1.6%) of the patients and 3 (0.7%) control subjects had other causes of infertility, and 47 (3.6%) patients and 9 (2.0%) control subjects did not have a complete infertility evaluation. Additional information on tubal morphology (hysterosalpingography, laparoscopy, or laparotomy) in women from couples for whom evaluation was incomplete indicated that 165 (12.2%) patients and 4 (0.9%) of the control subjects had abnormal tubal function or morphology after index laparoscopy. Tubal factor infertility after PID was associated with number and severity of PID episodes. The ectopic pregnancy rate for first pregnancy after index laparoscopy was 9.1% among the patients and 1.4% among control subjects. PMID- 1411833 TI - Comparison of polymerase chain reaction, monoclonal antibody based enzyme immunoassay, and cell culture for detection of Chlamydia trachomatis in genital specimens. AB - An enzyme immunoassay (EIA; AntigEnz Chlamydia; Northumbria Biologicals, Northumberland, United Kingdom) and a polymerase chain reaction (PCR) assay (Genemed Biotechnologies, San Francisco, CA) were evaluated for the detection of Chlamydia trachomatis in urogenital specimens. Of 324 specimens, 23 were positive by cycloheximide-treated McCoy's cell culture method. Of 23 culture-positive specimens, 20 and 22 were found to be positive by EIA and PCR, respectively. Among 301 culture-negative samples, 4 were found to be positive by both PCR and EIA, 2 were PCR-positive and EIA-negative, and 3 PCR-negative and culture negative specimens were found to be positive by EIA. In comparing nonculture methods with cell culture technique, combined sensitivities of 87.0% (90.9% in men and 83.3% in women) and 95.6% (90.9% in men and 100% in women), and specificities of 97.7% (99.4% in men and 95.7% in women) and 98.0% (99.4% in men and 96.5% in women) are achieved by EIA and PCR, respectively. The PCR proved to be the more sensitive of these two nonculture methods, and it can be used for the rapid diagnosis of C. trachomatis urogenital infection. PMID- 1411834 TI - Mucopurulent cervicitis as a predictor of chlamydial infection and adverse pregnancy outcome. The Investigators of the Johns Hopkins Study of Cervicitis and Adverse Pregnancy Outcome. AB - The role of mucopurulent cervicitis in identifying pregnant women with Chlamydia trachomatis infection and poor pregnancy outcome was examined at the Johns Hopkins Hospital Obstetric Clinic in Baltimore, Maryland. The women studied were at high risk for chlamydial infection (14%), low birthweight (12%), and preterm delivery (13%). Yellow endocervical discharge on a cotton swab had a sensitivity of 23.9%, specificity of 89.4%, and positive predictive value of 28.6% for predicting chlamydial infection. The presence of greater than or equal to 30 polymorphonuclear cells per 1000 x field had a sensitivity of 25.0%, specificity of 87.6% and positive predictive value of 24.3%. Women with cervicitis defined by greater than or equal to 30 polymorphonuclear cells per 1000 x field were twice as likely to deliver a low-birthweight infant. Adjustment for potential confounding variables did not explain this association. The poor sensitivity, specificity, and positive predictive value of mucopurulent cervicitis suggests that this parameter is not a useful screening tool for chlamydial infection in pregnant women. However, mucopurulent cervicitis may be an indicator of increased risk for poor pregnancy outcome. PMID- 1411835 TI - The emergence of penicillinase-producing Neisseria gonorrhoeae strains carrying the 4.9 kb (Toronto) plasmid in Denmark and of a novel large plasmid in two nonpenicillinase-producing Neisseria gonorrhoeae strains. AB - This study comprised plasmid analysis and antimicrobial susceptibility testing of 712 out of a total of 730 penicillinase-producing Neisseria gonorrhoeae (PPNG) and 744 random non-PPNG strains isolated in Denmark between 1985 and 1990. The rate of patients with PPNG infections rose from 1% to 2% during 1985-1987 to 6.9% in 1989, and then decreased to 4.8% in 1990. A decrease in cases of gonorrhea from 9,798 to 1,990 was seen during the same period. Strains harboring the 4.9 kb (Toronto) plasmid first appeared in 1987; in 1988-1990, 65% to 78% of strains from patients with PPNG infections acquired in Denmark contained this plasmid. The majority of these strains seemed to belong to a single clone. Tetracycline resistant PPNG strains (MIC greater than 32 mg/L) first appeared in Denmark in 1989, and tetracycline-resistant non-PPNG strains carrying a 40 kb plasmid (tetM?) first appeared in 1990. A novel 41-42 kb plasmid appeared in one strain in 1987 and another in 1988. The minimum inhibitory concentration (MIC) of tetracycline for these two strains was 4 mg/l. The significance of this plasmid is yet unknown. PMID- 1411836 TI - Temporal trends in gonococcal antibiotic resistance in Baltimore. AB - Each month from August 1986 through July 1990, clinical and laboratory data were evaluated for the first 25 urethral isolates of Neisseria gonorrhoeae from men attending a Baltimore sexually transmitted disease (STD) clinic as part of an effort to understand factors that contribute to changes in gonococcal antimicrobial susceptibility. During the 48-month study period, 1193 gonococcal isolates were evaluated; the proportion of penicillinase-producing N. gonorrhoeae (PPNG) isolates steadily increased, the prevalence of tetracycline-resistant N. gonorrhoeae (TRNG) remained relatively stable, and chromosomally mediated penicillin resistance increased steadily during the first 5 6-month intervals, then decreased, only to increase again during the final 2 6-month intervals. Changes in antibiotic treatment regimens for gonorrhea were associated with changes in the prevalence of chromosomally mediated penicillin resistance. In a supplementary study to characterize patterns of antibiotic use among men and women attending the STD clinics, 9% of patients reported antibiotic use in the 2 weeks prior to clinic visit. Antibiotics were taken prior to clinic attendance by 65% of patients reporting antibiotic use, because of concerns regarding possible STD or STD exposure. These patients were significantly less likely to be culture positive for N. gonorrhoeae when compared with patients who did not report antibiotic use. Temporal trends in N. gonorrhoeae antibiotic resistance appear to be influenced by many factors, including treatment regimens and self medication. PMID- 1411837 TI - Evaluation of an enzyme immunoassay and a modified coagglutination assay for typing gonococcal isolates with monoclonal antibodies. AB - In order to resolve methodologic and interpretation problems associated with the serotyping of Neisseria gonorrhoeae isolates with monoclonal antibodies specific for Protein I (PI) by coagglutination (the standard method; CoA1), two methods were compared with CoA1: an enzyme immunoassay (EIA) and a modified coagglutination assay (CoA2), in which methylene blue was added to the monoclonal antibody reagents. When the EIA was compared with the CoA1 method, 92.7% of the WI isolates were typed identically and 89% of the WII/III isolates were typed identically. When the CoA2 was compared with the CoA1 method, 92.7% of WI isolates were typed into similar serovars, in comparison to only 80.5% of the WII/III isolates. With the EIA method, only 21 of 328 isolates (6.4%) were retested because duplicate results were inconsistent, in comparison to 72 isolates (22%) with the CoA1 method and 120 isolates (36.6%) with the CoA2 method. In most cases result inconsistencies between duplicate tests were due to differences in reading weakly positive coagglutination reactions with single reagents (which on duplicate testing might be negative), the most notable being PIA reagent 4A12(b) and PIB reagents 1F5(b) and 2G2(g). The EIA method was the most reproducible method, and provides some degree of automation when serotyping large numbers of isolates. PMID- 1411838 TI - Effectiveness of latex condoms as a barrier to human immunodeficiency virus-sized particles under conditions of simulated use. AB - Condoms were tested in an in vitro system simulating key physical conditions that can influence viral particle leakage through condoms during actual coitus. The system quantitatively addresses pressure, pH, temperature, surfactant properties, and anatomical geometry. A suspension of fluorescence-labeled, 110-nm polystyrene microspheres models free human immunodeficiency virus (HIV) in semen, and condom leakage is detected spectrofluorometrically. Leakage of HIV-sized particles through latex condoms was detectable (P less than 0.03) for as many as 29 of the 89 condoms tested. Worst-case condom barrier effectiveness (fluid transfer prevention), however, is shown to be at least 10(4) times better than not using a condom at all, suggesting that condom use substantially reduces but does not eliminate the risk of HIV transmission. PMID- 1411839 TI - Sentinel surveillance of human immunodeficiency virus infection in sexually transmitted disease clinics in the United States. AB - From April 1988 through December 1989, sera obtained for syphilis testing from consecutive patients attending 98 sexually transmitted disease (STD) clinics in 37 metropolitan areas were tested for antibodies to human immunodeficiency virus (HIV) in an unlinked (blinded) survey. HIV seroprevalence in STD clinics ranged from 0 to 38.5% (median, 2.3%), with the highest rates found in the Mid-Atlantic states, Florida, and Puerto Rico. The highest median rates were found in men who have sex with men (36.1%) and heterosexual intravenous (IV) drug users (4.1%). For heterosexual persons who do not report IV drug use, median rates were highest in the 35- to 39-year-old age group for men (6.4%) and the 30- to 34-year-old age group for women (0.9%). Among persons who do not report risk behaviors for HIV infection, men had substantially higher median rates of HIV infection than women (P less than 0.001, Wilcoxon Signed Rank test), and rates were positively correlated with HIV infection rates in IV drug users in the same clinic (Pearson correlation coefficient [r] = 0.8; P less than 0.001). Among heterosexual STD clinic patients who do not report IV drug use, the median HIV infection rate for blacks (1.8%) was at least 2 times higher than the median infection rates for hispanics (0.9%) and whites (0.7%). The results of this study show that HIV infection in STD clinic patients varies by geographic area, sex, race and ethnic group, and risk behavior.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411840 TI - Condoms for men, not women. Results of brief promotion programs. AB - Three different brief intervention programs to promote condom use were tested among patients in inner-city sexually transmitted disease (STD) clinics. The first, "Condom Skills," focused on teaching mechanical aspects of how to use a condom. The second, "Social Influences," emphasized how to negotiate condom use with one's sexual partner. The third, "Distribution," provided patients with an unlimited number of free condoms, retrievable at local community businesses. Of the 903 subjects whose medical records were reviewed after exposure to the intervention programs, evidence of continued unsafe sexual behavior, documented by subsequent treatment for a new STD, was found for 12.6% of the women and 19.9% of the men. When compared with male control subjects, male study patients had fewer documented subsequent STD reinfections. The relative risk (RR) and 95% confidence interval (CI) values were 0.48 and 0.28, 0.81 for the condom skills group; 0.65 and 0.40, 1.04 for the social influences group; and 0.85 and 0.56, 1.29 for the distribution group. There was no decrease in the incidence of STDs among female patients compared with control subjects; indeed, there was a trend toward increased risk of STDs among women exposed to the Social Influences intervention program. This study demonstrates that brief condom promotion programs can be effective for male STD patients, and that caution must be exercised in promoting condoms to women with a high risk of acquiring STDs. Further research on programs promoting safer sex among these women is needed. PMID- 1411841 TI - Underdiagnosis of Chlamydia trachomatis infection. Diagnostic limitations in patients with low-level infection. AB - To determine limitations in commonly used methods for detection of Chlamydia trachomatis, 601 genitourinary specimens from patients in a sexually transmitted disease clinic were examined with quantitative cultures and by 2 different direct antigen tests, immunofluorescence (Micro Trak; Syva Company, Palo Alto, CA) and enzyme immunoassay (Chlamydiazyme; Abbott Laboratories, North Chicago, IL). Genital specimens were held no longer than 5 hours (at 4 degrees C) prior to inoculation for culture; 28% (168/601) were positive. To evaluate the effect of storage on culture efficacy, duplicate specimens were also stored at -70 degrees C and brought out subsequently for culture a second time. Only 32% (8/25) of specimens cultured within 5 hours and having less than 10 inclusions were positive on reculture, compared with 98% (49/50) positive for specimens with greater than or equal to 10 inclusions initially (P less than 0.001). Sensitivities of the two antigen tests were similar and taken together diminished significantly (P less than 0.001) as the number of organisms (inclusion forming units) in corresponding cultures decreased: 82% (51/62) sensitivity in cultures with greater than 100 inclusions; 50% (22/44) with 10-100 inclusions; and only 11% (6/53) with less than 10. Lack of urethral discharge in men with C. trachomatis infection (free of Neisseria gonorrhoeae) was associated with low numbers of inclusions (less than 10) and antigen tests failed in 68% (15/22) of these patients. PMID- 1411842 TI - High-risk behaviors for transmission of syphilis and human immunodeficiency virus among crack cocaine-using women. A case study from the Midwest. AB - This study examines the drug use patterns, sexual practices, condom use, knowledge and attitudes toward sexually transmitted diseases (STD)s and AIDS, and seroprevalence of human immunodeficiency virus (HIV) and syphilis among women who use crack in Dayton, Ohio. In 1990, two indigenous outreach workers recruited 150 participants who were not in drug treatment programs, who were 18 years of age or older, and had used crack in the previous 3 months. Structured interviews revealed that 90% of the sample were black, 78% used crack "daily," 93% had multiple sexual partners, and 49% had 10 or more male sexual partners in the last 3 months. A majority (67%) of the women felt they were in need of drug treatment. No reactive syphilis serologies were detected in 138 serum samples; 2 women (1.4%) were HIV seropositive. This case study provides insight into the high-risk sexual behaviors of crack users in a medium-sized, midwestern city. The study demonstrates the value of indigenous outreach prevention and STD screening initiatives in reaching this segment of our society, which has a high risk of acquiring STDs. PMID- 1411843 TI - Multiple partners and partner choice as risk factors for sexually transmitted disease among female college students. AB - Multiple sexual partners and partner choice are believed to increase the risk of sexually transmitted disease (STD), but these behaviors had not previously been assessed outside of clinical populations. In this study, a cross-sectional survey among single, white, female students in their senior year of college was conducted to measure the association between behavioral risk factors and the acquisition of self-reported STDs during college. The usable response rate was 47.2% (n = 467). The combined prevalence of chlamydial infection, gonorrhea, genital herpes, human papillomavirus (HPV) infection, syphilis, and trichomoniasis during a 3.5-year period was 11.7%. There was a strong association between number of sexual partners and having an STD: those women with 5 or more sexual partners were 8 times more likely to report having an STD than those with only 1 partner, even after adjusting for age at first intercourse (odds ratio = 8.1; 95% confidence interval = 1.99, 32.64). The prevalence of a history of STDs increased with more causal partner choice and earlier age at first intercourse, but neither factor was independently associated with a history of STDs. Of the respondents, 23% always used condoms. Future research should focus on identifying ways of effectively changing high-risk sexual behavior. PMID- 1411844 TI - The sexually transmitted diseases laboratory in a framework of population-based diagnostics. AB - Laboratory support for the diagnosis and treatment of sexually transmitted diseases has traditionally been within a patient-based diagnostic paradigm. Tests and interpretative criteria developed within this paradigm may not be appropriate for laboratories supporting population-based STD control programs. As STD control strategies expand to population-based levels, the present patient-based laboratory models will have to be modified to meet these increased demands. PMID- 1411845 TI - Patterns of antibiotic susceptibility of gonococci isolated in Hong Kong, 1987 1990. AB - Among the 14,528 strains of Neisseria gonorrhoeae isolated from the Government Social Hygiene Sexually Transmitted Disease (STD) Clinics in Hong Kong between 1987 and 1990, there has been a trend toward a decrease in the percentage of penicillin resistant strains in both penicillinase-producing and nonpenicillinase producing N. gonorrhoeae (PPNG and non-PPNG) and an increase in moderate resistant strains, whereas the proportion of sensitive strains has remained stable, except for a small increase in 1990. Presently, PPNG still accounts for 31% of all isolates. In early 1991, 100 consecutive isolates were tested for minimum inhibitory concentrations (MIC) against 6 commonly used antibiotics. Although ofloxacin has been used as the first-line treatment for gonorrhea for the last 5 years, there is still no sign of in vitro resistance. Two isolates with high-level tetracycline resistance (MIC greater than 16 mg/l) were detected that have not been seen before. Sensitivity to spectinomycin, cefuroxime, and ceftriaxone has also been maintained, and these drugs can probably be recommended as alternative treatments in noncompliant cases. Analysis of location of contact shows an increasing proportion of cases of gonorrhea from overseas, particularly from parts of China. Comparison with the limited information published in the region shows that the population sampled can be very heterogeneous. With the continued flux of international travel, one should be extremely careful when trying to get an accurate assessment of epidemiologic data. PMID- 1411846 TI - Fulminant endocarditis due to infection with penicillinase-producing Neisseria gonorrhoeae. AB - Endocarditis is a rare but potentially lethal manifestation of gonococcal infection. We report the case of a patient with fulminant endocarditis secondary to infection with penicillinase-producing Neisseria gonorrhoeae (PPNG). The patient had rapid deterioration from extensive destruction of the aortic valve with abscess and fistula formation. Lifesaving emergency surgery was performed. To our knowledge this is the first reported case of gonococcal endocarditis secondary to infection with a penicillinase-producing organism. PMID- 1411847 TI - Treatment of chancroid with a single dose of spectinomycin. AB - Fifty patients with lesions characteristic of chancroid were enrolled in an open label prospective study to examine the efficacy of a single 2-gm dose of spectinomycin for treatment of chancroid. Only those patients (41 men; aged 18 to 49 years) with positive culture results for Haemophilus ducreyi were included in the analysis. Patients each received a single 2-gm dose of spectinomycin intramuscularly. The recovery process began on the third day of follow-up, as evidenced by the occurrence of epithelialization and a decrease in inflammation. By the seventh day after treatment, only one patient had ulcers; 40 patients experienced eradication of all ulcers (P less than 0.0001). The condition of nodes affected by infection also indicated efficacy of treatment (P less than 0.01); only one patient still had a swollen node by the fourteenth day after treatment. Of the 41 patients, 37 (90%) had negative culture results for H. ducreyi on the third day after treatment. Only 4 patients (10%) required a second dose of spectinomycin on the seventh day to affect a cure. Treatment with spectinomycin resulted in a 98% cure rate 14 days after treatment. The minimum inhibitory concentration (MIC) of spectinomycin was 1 microgram/mL to 3 micrograms/mL in the 15 strains studied. The drug was well tolerated and no adverse reactions were reported. It is concluded that a single 2-gm dose of spectinomycin is a safe and effective alternative drug for treatment of chancroid. PMID- 1411848 TI - Split-dose metronidazole or single-dose tinidazole for the treatment of vaginal trichomoniasis. AB - In a double-blind, randomized, controlled trial, efficacy and safety of a single day split dose of 1.6 g of metronidazole were compared with a single 2-g dose of tinidazole in the treatment of vaginal trichomoniasis. Women with symptomatic vaginal trichomoniasis were randomly assigned to one of the two treatment groups. There were 67 women in the group treated with the single-day split dose and 65 in group treated with the single dose. There was no significant difference between the two groups in terms of clinical characteristics (age, weight, and length of follow-up period). The cure rates, using trypticase yeast extract iron serum (TYI) medium to confirm microbiologic cure, were 98.5% and 100% for the groups treated with a single-day split dose and with a single dose, respectively. The side effects were minimal and did not warrant any treatment. The differences in the results were not statistically significant. We recommend that the single-day split dose of 1.6 g of metronidazole regimen be given as an alternative drug for vaginal trichomoniasis. Its advantages include being highly effective, significantly less expensive, and with minimal side effects. PMID- 1411849 TI - Prevalence of sexually transmitted disease infection in women alleging rape. AB - During a 2-year period ending in October, 1989, 110 women who claimed to have been raped were treated at the sexually transmitted disease clinic at Birmingham General Hospital. A total of 22 sexually transmitted infections were found in 14 (13%) women, of which Chlamydia trachomatis (in 8%) and Trichomonas vaginalis (in 6%) were the most frequently found pathogens. In none of these patients was it possible to determine whether infection resulted from rape or from voluntary intercourse with another person. The high prevalence of infection found in this study and in previous studies indicates that all women alleging rape should be investigated at a sexually transmitted disease clinic. PMID- 1411850 TI - Epidemiology of low-back pain in industry. AB - Low-back pain and back injuries are of such a complex nature that any one criterion cannot be applied by itself to give a valid assessment of the risk associated with manual materials-handling jobs. There is no question that low back pain is an extremely significant cause of disability and has a major socioeconomic impact, but many different personal and job factors are associated with the incidence and prevalence of these complaints. There is a need for ongoing systematic investigations of the multiple risk factors that may be causally related to low-back pain and may possibly be amendable to preventive interventions. Knowledge of workplace and individual risk factors is far from complete. Prospective studies are needed so that factors contributing to the development of low-back pain can be separated from factors resulting from low back pain. It is difficult to relate low-back pain to the workplace because it occurs quite often in workers employed in sedentary occupations. However, incidence, severity, and disability are all related to the physical demands of the job. In this regard, jobs involving lifting, lowering, pushing, pulling, carrying, and holding; body movements such as frequent bending, twisting, and sudden movements; and working in bent-over postures appear to have a significant potential for producing low-back pain. A combination of lifting, bending, and twisting appears to be most hazardous. It is concluded that lifting heavy loads contributes to increased frequency and severity rates for low-back pain. This is true regardless of whether the lifting is performed over a short period or throughout the day and whether it is performed a few times per day of repetitively. If, however, such lifting is performed repetitively, the medical hazard extends beyond low-back problems to other musculoskeletal strain and sprain injuries and to fatigue-related injuries, particularly for weaker workers. In this latter regard, gender, age, anthropometry, and previous history of back pain are known to modify these risks for populations of workers. The inherent variability between workers and within any worker over time precludes the use of such factors to assign risk to any particular individual. PMID- 1411851 TI - Occupational biomechanics and low-back pain. AB - The basic principles of biomechanics are introduced and explained as they relate to the field of ergonomics, especially regarding the lumbar spine. The discussion is organized into the following sections: biomechanics--an overview, spinal structures and loading, biomechanical basis for low-back pain, compressive strength of the lumbar spinal column, biomechanical models, intra-abdominal pressure, lifting technique, and practical applications. The conclusion lists nine guidelines for understanding the internal stresses placed on the lower back by lifting and thereby for avoiding low-back injuries in the workplace. PMID- 1411852 TI - Prevention strategies and the low back in industry. AB - Several different approaches have been tried in industry to prevent low-back injuries. The scientific literature shows that only job-specific strength testing and ergonomic job design are partially effective in preventing low-back injuries. Job-specific strength testing is supported as a means of identifying high-risk workers who need to perform manual materials handling. However, this approach should be carefully validated for its effectiveness before it is used as a form of selection procedure. At present, ergonomic job design offers the most potential for preventing disabling low-back injuries and other musculoskeletal injuries. Quantitative and objective methods (such as NIOSH guidelines, biomechanical models, energy expenditure, and strength data) are available to analyze a given job and to determine the relative risk of an injury. PMID- 1411853 TI - Diagnoses and treatment options in occupational low-back pain. AB - Job modification is often effective for prevention of LBP, but employee selection is generally risky, unreliable, and (increasingly) illegal. For acute care, excellent results are obtained with a simple, well-organized protocol. A trial of additional interventions is usually not productive. In rehabilitation, the challenge is to choose interventions at the most cost-effective time and identify local programs which have proven effectiveness. Case-closure issues such as medical end-result, impairment rating, and permanent job restrictions continue to be poorly supported by scientific literature. They are often best resolved by consensus of the patient, physician, and employer. We look forward to more reliable predictors of long-term outcome. An old adage says, "If there are dozens of treatments for a disease, probably none of them is effective." In recent years we have advanced from dozens of equally acceptable treatments to a few well documented ones, as outlined in the Quebec study. Such an approach is very effective in changing the course of back pain. However, there are still many unproven treatments in common use. Perhaps some will prove useful. In adding interventions to a simple, effective protocol, one must be aware of the true risks and benefits. PMID- 1411854 TI - Toward an understanding of dynamic variables in ergonomics. AB - Although researchers have shown that dynamic activity may greatly increase the predicted loading experienced by a joint, most ergonomic assessments in the workplace have focused on the postures of the workers and the loads imposed on a joint due to these postures, ignoring the influence of dynamic motion on joint loading. Current technologic advancements now allow the performance of dynamic ergonomic assessments that were impossible a few years ago. This chapter reviews the recent efforts to understand how occupational settings influence the joint motions and subsequent risk of suffering an injury or illness, including the effect of trunk motion on the reaction of joint-supporting structures and the subsequent loading of the spine and wrist. The back appears to be sensitive to the velocity component of motion, and the wrist to acceleration. PMID- 1411855 TI - A functional job analysis technique. AB - An analytical approach is presented for evaluating functional job demands and for facilitating a team problem-solving process that should find cost-effective resolutions for designs that do not meet ergonomic guidelines. Information is included on ways to collect information about the job elements and demands, how to relate the demands to population work capacities, how to predict fatiguing tasks, and how to facilitate a problem-solving session within the plant or business. A case study is used to illustrate the process from the initial review of jobs in a plant to the generation of a list of possible actions and their expected benefits. PMID- 1411856 TI - Function, structure, and responses of components of the muscle-tendon unit. AB - A "muscle-tendon unit" is a composite structure that includes muscle, tendon, myotendon junctions, tendon sheaths, and tendon-bone junctions. Each component is unique in its structure, function, response to strain, and associated clinical disorders (usually called "tendinitis"). Tendinitis implies localized tenderness in the distribution of a muscle-tendon unit to palpation, passive stretching, or active contraction. A variety of distinct clinical entities associated with the various components of the muscle-tendon unit are usually grouped together under the term "tendinitis," although each has unique characteristics and etiologic factors. Most have short latencies and favorable prognoses with appropriate clinical management, and most also bear some direct relationship to biomechanical factors, such as compression or strain, as well as to work organizational factors, particularly unaccustomed work. PMID- 1411857 TI - Carpal tunnel syndrome. AB - Despite numerous publications in the literature, there is still a significant deficit of knowledge regarding carpal tunnel syndrome and its relationship to work. This chapter reviews a variety of observations from these studies. Epidemiologic studies have been mostly cross-sectional surveys using clinical criteria (symptoms and physical findings) as a basis for case definition, but these exposure assessments cannot discriminate between work-related and non-work related cases of carpal tunnel syndrome. These studies do reveal a fairly consistent pattern of observations regarding the spectrum and relative frequency of upper extremity morbidity among jobs believed to be hazardous. Carpal tunnel syndrome, however, is but one of these disorders and is not the most common one. Historical perspectives, anatomic pathology, pathophysiology, theories of pathogenesis, epidemiologic observations, associations with exposure, and current issues are discussed. PMID- 1411858 TI - [Phakomatosis: anatomo-clinical expressions of urological interest]. AB - Up to date etiopathogenetic knowledge of phakomatoses allows a more rational classification as compared to the known ones, based on anatomopathological and/or clinical features. Some genes have been identified, which are correlated with neurofibromatoses, tuberous sclerosis and other conditions, through general biologic mechanisms (derivatives of the embryonic neural crest; nerve growth factor and its receptor; oncogenes and antioncogenes, etc.). A prenatal predictive value from those genetic connections can also ensue. The new diagnostics, both by imaging and by laboratory techniques, may affect the therapeutic choices, as for as urological involvement is concerned. PMID- 1411859 TI - [Bilateral non-Hodgkin's lymphoma of the adrenal gland. Report of 2 cases]. PMID- 1411860 TI - [Aneurysm of the renal artery mimicking a cyst]. AB - Renal artery aneurysms are not frequent, insidious clinico-pathological entities. They are often asymptomatic and cannot be readily differentiated from renal cysts on routine US. The Author presents a case with fatal outcome and stresses the need of Doppler testing before cyst puncture for diagnostic or therapeutic purpose. PMID- 1411861 TI - [A case of epididymal lymphangioma]. PMID- 1411862 TI - [A case of human dirofilariasis (D. repens) of the spermatic cord]. AB - A 52 year old man, living in the province of Trapani (Sicily), presented with right hydrocele and slight orchialgia. The patient underwent epididymectomy and resection of T. vaginalis. The "tunica" was involved by a granulomatous process, containing a parasite of genus Dirofilaria (D. repens). Dirofilaria repens is a filarial nematode. Dogs, foxes and cats are the definitive hosts and principal reservoirs of the parasite. In humans the parasite dies before reaching sexual maturity and the result is an inconspicuous granulomatous reaction in the subcutaneous tissue. S. Pampiglione et al. (Cattedra di Parassitologia Veterinaria dell'Universita di Bologna-Italy) reported from 1971 more than 30 cases of human Dirofilariasis in Italy, suggesting that the parasite is able to migrate from the inoculation site to other districts (lung, eye etc.). The case is exceptional for the localization of the parasite (never reported) and can contribute to a better knowledge of the disease. PMID- 1411863 TI - [A case of retroperitoneal leiomyosarcoma]. AB - The Authors present a case of retroperitoneal leiomyosarcoma, diagnosed because of the early symptomatic hydronephrosis due to the compression of the tumour on the lumbar ureter. Some general clinical aspects of retroperitoneal sarcomas are discussed too. In the case presented adjuvant therapy was not advised, because of the small volume of the tumour and the possibility of its complete excision. PMID- 1411864 TI - [Retroperitoneal malignant mesenchymoma in a patient subjected to exeresis of an epididymal leiomyoma]. PMID- 1411865 TI - [Hemo-rheologic changes following treatment with human recombinant erythropoietin in chronic hemodialysis patients]. AB - Human recombinant erythropoietin constitutes a remarkable improvement in the treatment of uraemic anemia. Nevertheless, it causes haemorheological changes, which in turn may affect smaller blood vessel circulation. Our study was conducted on a pool of chronic uraemic patients under hemodialytic treatment who were given erythropoietin therapy. Substantial increases in overall blood viscosity and red cell aggregation were recorded, with no change in erythrocyte deformation. An increase in cardiovascular morbidity might occur in these patients who are already liable to this condition. Several years will have to elapse and thorough studies will have to be conducted on a large number of patients, to have conclusive evidence on this point. PMID- 1411866 TI - [Clinical evaluation of 12 months of biofiltration in an elderly group]. AB - Biofiltration (BF) was performed on 8 elderly uraemic patients (mean age 73.75 +/ 8.72 years; dialytic age 75.00 +/- 38.42 months) to improve cardiovascular stability and to reduce the dialytic session time. Small molecules (nitrogen, creatinine, uric acid, phosphorus) depuration, heamogasanalysis and PA monitoring, were compared against previous datum obtained by the same group that had undergoing acetate dialysis (AC. HD) for a year. Small molecules showed no significant differences; in BF the incidence of symptomatic hypotensions and the dialytic session time were reduced (30% and 30 min. respectively), with a better metabolic acidosis correction versus AC.HD. Our results showed that BF is better than AC.HD in elderly uraemic patients. PMID- 1411867 TI - [Efficacy and safety of simvastatin in the treatment of hyperlipidemia in uremic patients undergoing hemodialysis treatment]. AB - The efficacy, tolerability and safety of simvastatin in the treatment of hyperlipemia in uremic patients undergoing hemodialysis were evaluated in 6 patients; a further 6 patients were treated with placebo and represented the control group. All patients treated completed the study. No clinical or laboratory side-effects were noted during the entire period of observation. Simvastatin caused a significant 26% reduction in total cholesterol, a 36% reduction in LDL cholesterol and a 28% reduction in triglycerides; HDL cholesterol and Apolipoprotein A increased by 19% and 12% respectively. PMID- 1411868 TI - [Neoplasia of the testis: surgical, radiological, and chemotherapeutic approach. Analysis and results of a retrospective study]. AB - The Authors report the results of a retrospective study in patients with testicular cancer admitted to hospital between January 1979 and July 1991. A total of 59 cases of testicular cancer were treated: 42 seminomatous and 17 non seminomatous. Radiotherapy was carried out with satisfactory results in patients with stage 1 and 2 seminoma (22 cases). A "wait and see" policy was adopted in 2 cases. The majority of non-seminomatous tumours underwent retroperitoneal lymphadenectomy followed by chemo- and/or radiotherapy (9 cases). Retroperitoneal lymphadenectomy plays a vital role in correct pathological staging and the evaluation of neoadjuvant chemotherapy. PMID- 1411869 TI - [Squamous metaplasia as a prognostic factor in urothelial carcinoma of the bladder]. AB - The Authors report a retrospective review of 224 cases of transitional cell carcinoma of the bladder observed between 1986 and 1990. Squamous metaplasia was present in 45 case. This histological feature was found especially in association with poorly differentiated and invasive tumours: the presence of extensive areas of squamous metaplasia (metaplastic areas = or greater than 50% of neoplastic surface) was always found in association with high grade neoplasms and with a disease-free period shorter than transitional cell carcinoma. The Authors conclude that squamous metaplasia in transitional cell carcinoma of the bladder is a really unfavourable prognostic factor. PMID- 1411870 TI - [When does a child begin to have pain?]. PMID- 1411871 TI - [The Gustave Roussy child pain scale]. PMID- 1411872 TI - [These examinations hurt]. PMID- 1411873 TI - [The pain of the child with cancer]. PMID- 1411874 TI - [Patient controlled analgesia]. PMID- 1411875 TI - [The child with pain]. PMID- 1411876 TI - [Pain in children]. PMID- 1411877 TI - [Pain in the child. Role of the nursing staff]. PMID- 1411878 TI - [Management of pain in neonatology]. PMID- 1411879 TI - [The PEDIADOL databank]. PMID- 1411880 TI - [Reasons for the delay]. PMID- 1411882 TI - [Breast nodule]. PMID- 1411881 TI - [Maternal lactation]. PMID- 1411883 TI - [Physiology of pain]. PMID- 1411884 TI - Long term results of percutaneous catheter drainage of pancreatic pseudocysts. AB - Percutaneous catheter drainage (PCD) has become an established and often preferred alternative to surgical treatment in the management of pancreatic pseudocysts. However, the long term results of percutaneous drainage of pancreatic pseudocysts remain uncertain. In an effort to determine the long term outcome of this therapy, 42 patients undergoing PCD of a pancreatic pseudocyst were analyzed retrospectively. Forty-two pancreatic pseudocysts were drained percutaneously in 42 patients. Sixty-seven percutaneous drainage procedures were performed--22 patients underwent one, 15 had two and five patients required three procedures. Percutaneous drainage was considered not to be effective when the pseudocyst persisted or when it recurred after initial resolution. Twenty-three pseudocysts were infected at the time of drainage and 19 were not infected. In 30 patients, the cause of the pseudocyst was alcoholic pancreatitis. There were no deaths related to the procedures and seven complications occurred, including hemorrhage, pancreatic fistula and empyema. Mean follow-up evaluation time of the patients was ten months. In nine patients, the pseudocyst was successfully drained and resolved. There were 33 treatment failures, among which 26 pseudocysts failed to resolve and seven recurred after initial resolution. Eventually, 25 patients underwent a surgical procedure, 20 for persistent pseudocyst and five for recurrence. Using contingency table analysis, the size of the pseudocyst, amount of fluid drained, amylase concentration in the aspirate, presence of infection, number of drainage procedures performed and duration of catheter drainage had no influence on the likelihood of success in long term pseudocyst resolution after PCD. Pseudocysts not related to alcoholic pancreatitis seemed to be less likely (p < 0.05) to resolve with percutaneous drainage than those caused by alcohol. PCD is a safe and valuable procedure in the acute management of patients with pancreatic pseudocyst. However, the current data suggest that despite early success with percutaneous drainage, the lack of resolution and recurrence rate of pancreatic pseudocyst is high. Therefore, it should not be considered as the definitive form of therapy in most patients. Close surveillance of patients undergoing percutaneous drainage and communication between surgeons and radiologists are critical in the management of pancreatic pseudocysts. PMID- 1411885 TI - Management of periareolar abscess and mamillary fistula. AB - During a 15 year period, 18 patients with 28 mamillary fistulas were treated. In eight women, periareolar abscess had preceded recognition of a fistula. Ten patients were primarily diagnosed as having mamillary fistula. In six patients, when the underlying fistula tract was not identified and excised at the time of operation, discharging sinus reoccurred. Twenty-two fistulas were completely excised together with an extensive lactiferous duct system. Operative wound was primarily closed using antibiotic cover. Periareolar abscess and mamillary fistula should be treated primarily by complete excision of the fistula tract and extensive duct system of the breast. PMID- 1411886 TI - Venous and arterial anomalies of the lower extremities diagnosed by duplex scanning. AB - The complex embryologic development of the vascular system often results in a myriad of clinically relevant anomalies. It has been stated that the classic anatomic venous pattern in the lower extremity is found in only 16 percent of patients. Previous studies on this topic are limited to isolated venous dissections or phlebography that lack complete anatomic detail. The recent introduction of high resolution duplex scanners for the assessment of veins of the lower extremity provides a unique opportunity to determine the incidence of anatomic variation. The current prospective study was done to identify venous or arterial anomalies apparent during routine duplex scanning of the lower extremity performed to rule out deep venous thrombosis (DVT). Limbs that had evidence of acute or chronic extensive DVT were excluded. Of 1,600 consecutive extremity scans, 946 extremities (59 percent) had no evidence of DVT. Of these, there were 43 patients with 64 anomalies in 57 extremities. The mean age of the group was 53.4 years. There were 24 women (55.8 percent) and 19 men (44.2 percent). There were 59 (92.2 percent) venous and five (7.8 percent) arterial anomalies. Duplication of the superficial femoral vein was the most common anomaly noted. Duplication of the deep femoral and popliteal vein was also noted. Unilateral anomalies were more common than bilateral anomalies, namely 67.4 versus 32.6 percent, respectively. Pain and swelling, common complaints in the patients with an anomaly, were noted in 71.4 and 45.7 percent, respectively. The frequency of deep venous anomalies of the lower extremities may be less than previously reported. Knowledge concerning the incidence and distribution of venous anomalies may lead to improved assessment and treatment of venous disease. PMID- 1411887 TI - Preliminary results of a prospective randomized study of Cooper's ligament versus Shouldice herniorrhaphy technique. AB - Surgeons have developed many methods for the repair of direct inguinal hernias. The Cooper's ligament (McVay) repair and the Shouldice repair are widely used techniques. To determine the recurrence rates with differing techniques performed in a surgery residency program, we conducted a prospective randomized study for elective adult direct inguinal herniorrhaphies. Three hundred and eight elective direct inguinal herniorrhaphies in 269 adult patients were performed by residents in general surgery supervised by staff surgeons. Patients had yearly follow-up physical examinations (compliance rate of 87 percent) during an average follow-up period of 36.4 months. The recurrence rate was 8.8 percent for the McVay repair and 6.6 percent for the Shouldice repair (not significant). Bilateral inguinal hernias (repaired six weeks apart) had a recurrence rate of 12.8 percent, while the recurrence rate for unilateral repairs was 5.6 percent (p = <0.05). We found no significant difference in recurrence rates between the McVay and Shouldice herniorrhaphy techniques. However, there was an increase in hernia recurrence with either technique when bilateral direct inguinal herniorrhaphies were performed. PMID- 1411888 TI - The risk of perforation when children with possible appendicitis are observed in the hospital. AB - The morbidity rate from perforation demands that appendicitis be diagnosed promptly in children with abdominal pain. Although admitting and observing uncertain instances of appendicitis can refine the diagnostic accuracy, it is often claimed, but not proved, that this necessitates increasing the number of perforations. To assess the risk of perforation while observing uncertain instances of childhood appendicitis, we admitted 150 consecutive referrals during a period of one and one-half years. Immediate appendectomy was performed for 74 patients (49 percent) with convincing clinical signs and symptoms for appendicitis. The remaining 76 (51 percent) with unconvincing clinical signs and symptoms were observed as inpatients. One-third of the patients admitted for observation (26 of 76) underwent appendectomy after an average period of 12 hours. Two-thirds (50 of 76) of the patients got better and were discharged from the hospital without an appendectomy after an average admission of two days. Seven of the 100 appendices removed were normal. Three of the observed patients had perforations, one of whom may have perforated during observation, but that child went on to do well. The 50 patients who got well without appendectomy were similar to the patients with appendicitis, but significantly less likely to have peritoneal signs (8 versus 70 percent), tenderness in the right lower quadrant (48 versus 81 percent) and guarding (19 versus 75 percent). We conclude that admission and active observation in the hospital of children with possible, but unconvincing, signs and symptoms of appendicitis is a safe and effective way to determine which patients need an operation. PMID- 1411889 TI - Palpable abnormalities of the breast not requiring excisional biopsy. AB - The evaluation of a patient with a palpable abnormality of the breast typically includes physical examination, mammography and fine needle aspiration biopsy (FNAB) with cytologic interpretation of the aspirate. If the findings of these three diagnostic modalities are negative for malignancy, the current standard of care is to proceed to surgical biopsy to confirm the benign nature of the lesion. The current study was done to identify a subset of patients who could be safely observed without surgical (histologic) biopsy. These patients fulfilled specified criteria on physical examination, mammogram and needle sensation when the FNAB needle entered the lesion. Results of the cytologic studies of the FNAB were used as a corroborative rather than as a diagnostic test. Of 305 patients with mammary abnormalities, 106 were identified with "subsuspicious" lesions. Seven of the latter patients underwent surgical biopsy, four because the results of cytologic studies of FNAB revealed cytologic atypia. One of the four patients had infiltrating ductal carcinoma. All other patients have had follow-up evaluation for a mean of 61 months (range of 43 to 74 months). No carcinomas have developed at the subsuspicious site. The current study is the first to clearly define a subset of patients with palpable abnormalities of the breast who do not require surgical biopsy. PMID- 1411890 TI - Effect of prostaglandin E on immune function in normal healthy volunteers. AB - Prostaglandin E (PGE) has been hypothesized to be the endogenous metabolite that results in the immunosuppression seen in patients with tumor and trauma. This has resulted in multiple investigators proposing that administration of PGE inhibitors, such as aspirin and indomethacin, might improve immune function in such patients. We administered a long acting PGE analog, misoprostol, to nine normal healthy volunteers for five days and assayed immune function before and after therapy. The PGE analog improved lymphocyte blastogenesis and increased tumor necrosis factor production. The PGE analog also resulted in the volunteers having symptoms similar to those seen in patients with sepsis. The results of these studies indicate that elevated levels of PGE do not seem to result in impairment of immune function, but may be the endogenous metabolite responsible for the symptologic factors seen in infected patients. PMID- 1411891 TI - Prospective randomized study to compare a closed vault technique using absorbable staples at the time of abdominal hysterectomy versus open vault technique. AB - The current prospective randomized study in 102 women having a hysterectomy compared closed vault technique using absorbable staples with open vault technique. Fifty-six patients had the cuff stapled while 46 patients had the vault sutured open. The groups were equivalent with respect to indications for operation as well as other surgical procedures performed in conjunction with the hysterectomy, although more patients were randomized to open vault. No patient left the study. Operating time in the group with staples was 24 minutes (standard deviation of seven minutes) compared with 33 minutes (standard deviation of eight minutes) with the group with the open vault (p<0.0001). Hemostasis was also better in the group with staples (p<0.0001). The frequency of postoperative granulation tissue at the apex of the vaginal vault and the incidence of vaginal discharge during 12 weeks of follow-up evaluation were also less in the group with staples. PMID- 1411892 TI - Hemodynamic, hematologic and eicosanoid mediated mechanisms in 7.5 percent sodium chloride treatment of uncontrolled hemorrhagic shock. AB - Hypertonic saline solution (HTS) (7.5 percent sodium chloride [NaCl]) treatment (5 milliliters per kilogram) of rats subjected to uncontrolled hemorrhagic shock (n = 7) caused an initial partial recovery of blood pressure (+38 +/- 5 percent, p<0.05) and cardiac index (+48 +/- 6 percent, p<0.01) followed by increased bleeding (+53 +/- 5 percent versus rats treated with 0.9 percent NaCl, p<0.05), secondary shock (mean arterial pressure [MAP] 23 +/- 7 millimeters of mercury, p<0.01) and decreased survival (-54 +/- 15 minutes versus control, p<0.05). The increased blood loss resulted from: 1, increased vascular pressure and vasodilatation (total peripheral resistance index -27 +/- 5 percent, p<0.05), as initial bleeding occurred when MAP and cardiac index are increased compared with the control group (+88 +/- 10 percent, p<0.05 and +82 +/- 7 percent, p<0.01, respectively) and as the concomitant infusion of angiotensin II, a potent vasoconstrictor, delayed the HTS-induced bleeding (resumed at 60 minutes), and 2, a defect in platelet aggregation reflected by decreased adenosine diphosphate (ADP)-induced maximal aggregation (-79 percent versus rats treated with 0.9 percent NaCl, p<0.05) and increased EC50 of ADP (+159 percent, p<0.05). These hemodynamic and hematologic responses might be mediated at least in part by prostacyclin, a vasodilator and antiplatelet aggregator, as HTS-treated rats markedly elevated the 6-keto-PGF1 alpha per thromboxane B2 ratio (+140 +/- 12 percent, p<0.01) and pretreatment with indomethacin decreased blood loss and improved MAP and survival. These data point out potential untoward hemodynamic and hematologic consequences of HTS treatment in traumatic injury in which control of bleeding cannot be confirmed. PMID- 1411893 TI - Serum amylase levels in gynecologic patients with acute abdominal pain. AB - Total amylase and salivary (S) type isoamylase were measured in serum from 80 women with acute abdominal pain admitted to the Department of Gynecology. Fifty seven patients had verified gynecologic diseases, including 21 patients with inflammation of the internal genitals and 11 with ectopic pregnancy. Twelve patients had an intrauterine pregnancy in the first trimester. None of the 80 patients showed hyperamylasemia. PMID- 1411894 TI - A single technique for polypropylene mesh hernioplasty of inguinal and femoral hernias. AB - The main factor in the repair of groin hernias is the reinforcement of posterior wall defects of the inguinal canal, including the femoral ring, because the normal insertion of the transversalis fascia and transversus abdominis muscle is on Cooper's ligament and not Poupart's ligament. In approximately one-half of primary femoral hernia repairs in men, a coincidental ipsilateral inguinal hernia existed. Recurrence after inguinal herniorrhaphy is usually femoral. Forty-three patients with direct, large indirect or femoral hernias (primary or recurrent) had a Marlex mesh hernioplasty to treat the inguinal and femoral region simultaneously. PMID- 1411895 TI - Long term central vascular access through the gonadal vein. AB - A technique for long term central venous access through the gonadal vein is described. It has been used five times in four patients with consistently satisfactory results. PMID- 1411896 TI - From Hunter and the Great Pox to Jenner and smallpox. PMID- 1411897 TI - The wandering spleen. AB - Wandering spleen is an unusual entity, occurring in both sexes and at any age, but is more frequent in women of reproductive age and in children. Wandering spleen is probably most often a result of congenital anomalies of development of the dorsal mesogastrium, but acquired factors may have a role in certain instances. Patients present most commonly with an asymptomatic mass, mass and subacute abdominal or gastrointestinal complaints or with acute abdominal findings. Clinical diagnosis can be difficult, but noninvasive imaging procedures, such as sonography, nuclear scintigraphy, computed tomography and magnetic resonance imaging are usually diagnostic. Laboratory tests are usually nonspecific, but may occasionally reveal evidence of hypersplenism or functional splenia. Symptoms may remain limited or absent for long periods of time, but complications related to torsion or compression of abdominal organs by the spleen or the pedicle are quite common. Splenomegaly is usually a result of torsion of the pedicle and splenic sequestration. Significant morbidity and mortality rates seem to be considerably less than described in 1933 and limited primarily to patients presenting initially with acute abdominal findings. Management recommendations have varied, but recognition of a significant risk of postsplenectomy sepsis supports a conservative approach. Patients with limited symptomatology may be medically managed until they exhibit worsening symptoms indicating progressive splenic torsion or gastrointestinal compression. Detorsion and splenopexy may be considered a reasonable surgical option even in patients presenting with acute abdomen, if there is no evidence of infarction, thrombosis or hypersplenism. Splenic preservation is especially recommended in extremely young patients who are at particular risk for postsplenectomy sepsis. However, it should be noted that follow-up evaluation data on splenopexy patients are notably lacking. Splenectomy is ideally reserved for patients presenting with acute abdomen and splenic infarction or thrombosis or with hypersplenism and patients in whom splenopexy is technically unfeasible. Subtotal splenectomy and splenic autotransplantation may be of limited value. Pneumococcal, Hemophilus and meningococcal vaccines are indicated before elective splenectomy and shortly after nonelective splenectomy. Antibiotic prophylaxis is recommended for those at particular risk. Prospective studies are unlikely, but extended follow-up information on patients already reported, particularly those managed expectantly or with conservative surgical measures, is needed. PMID- 1411898 TI - The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system. AB - Dendritic cells form a system of antigen-presenting cells that is widely distributed in the body. They constitute trace populations in lymphoid and non lymphoid tissues and in the circulation. They are characterized by their typical dendritic and "veiled" morphology, by their constitutive expression of high levels of major histocompatibility complex class II molecules on their surface, and by their outstanding capacity to initiate primary immune responses. Dendritic cells occur in two states of differentiation. In the immature state they are highly specialized for processing foreign protein antigens; in the mature state they efficiently stimulate resting antigen-specific T cells. Dendritic cells can migrate from the non-lymphoid tissues, where they reside in the immature state, via the afferent lymphatics or the blood to the T cell-dependent areas of the lymphoid organs (lymph nodes, spleen). There, they appear as mature dendritic cells. Therefore, dendritic cells are ideally suited to mediate important aspects of immunogenicity: they can acquire antigens in the tissues and process them in an immunogenic form; they can carry the immunogen to the lymphoid organs; and they can find and efficiently activate antigen-specific T cell clones and thus generate an immune response. Studies of epidermal Langerhans cells have greatly helped in establishing this concept. They can be investigated freshly isolated from the epidermis where they represent immature (tissue) dendritic cells. After 2-3 days in culture they develop into mature dendritic cells. The mechanisms of dendritic cell maturation, which can be studied best using epidermal Langerhans cells, and the specific functions of Langerhans cells in immunogenicity are discussed. PMID- 1411899 TI - Induction of T helper cell subsets. PMID- 1411900 TI - T cells in allergic responses to haptens and proteins. PMID- 1411901 TI - Keratinocyte-derived tumor necrosis factor and the physiopathology of the skin. PMID- 1411902 TI - Leukocyte-endothelium interactions in cutaneous inflammatory processes. PMID- 1411903 TI - Induction and control of lichenoid tissue reactions. PMID- 1411904 TI - Cutaneous lymphoproliferative disorders: strategies for molecular biological analysis and their major findings. AB - This article focuses on the principal molecular biological methods that have been devised to study cutaneous lymphoid infiltrates. These methods involve analysis of antigen receptor gene rearrangements, chromosomal translocations and proviral integration using Southern blot analysis and gene amplification techniques. The major findings are discussed that pertain to early diagnosis, staging, disease monitoring, the development of new immunopathological assays and the detection of tumor-associated retroviruses. PMID- 1411905 TI - Recent advances on the 180-kDa epidermal antigen in autoimmune subepidermal bullous skin diseases. AB - The blistering skin disease bullous pemphigoid (BP) is an example of how autoantibodies from patients can be used as tools to improve our knowledge of the molecular structure of normal skin. BP autoantibodies bind to the basement membrane zone of normal human skin and usually react with two main epidermal antigens of approximately 230-kDa and 180-kDa. From recent studies, it is now established that the 180-kDa polypeptide is distinct from the 230-kDa BP antigen and is a major component of hemidesmosome. In this article, the recent data regarding the localization and structure of the epidermal 180-kDa BP antigen are reviewed in detail, together with its clinical significance, since it appears to be also a target antigen for pemphigoid (herpes) gestationis and, perhaps, cicatricial pemphigoid autoantibodies. PMID- 1411906 TI - T cell and cytokine patterns in leprosy skin lesions. PMID- 1411907 TI - Immunopathology of atopic dermatitis. PMID- 1411909 TI - International longevity comparisons. AB - Japan leads the world in life expectancy with an average future lifetime of 78.9 years. Iceland is next, followed by Sweden and Switzerland. The United States ranks 11th at 75.4 years. In the past decade, United States' men generally narrowed the expectation of life gap among other industrialized nations, but for the country's women the experience was uneven. These international longevity disparities for men and women in the United States narrowed considerably at later years of age. For instance, the United States-Japan expectancy gap is currently 2.0 years at age 45 and declines to about 0.9 years at age 65. PMID- 1411910 TI - Coronary artery bypass grafts: 1990 charges update. AB - During 1990, coronary artery bypass graft (CABG) operation charges among MetLife group health policyholders and dependents averaged $43,370. Among the 16 states with at least 50 CABGs, the total charges ranged from a high of $59,870 in California, to a low of $32,500 in Wisconsin. Three-fourths of the total was due to the hospital bill, with wide variation by state. The New York hospital proportion of total charges was the lowest (64 percent), whereas hospital charges in Alabama averaged 80 percent of the bill for a CABG. Physician charges averaged $11,220 across the country, ranging from $15,170 in California to $8,280 in Tennessee. Hospital stay averaged 11.6 days; patients in California and Alabama remained hospitalized for 10.2 and 10.3 days, respectively, whereas those in New Jersey had hospital stays of 16.1 days. PMID- 1411908 TI - Immunological mechanisms involved in psoriasis. PMID- 1411911 TI - U.S. longevity at a standstill. AB - Life expectancy in the United States did not increase during 1991, remaining at the 1990 level of 75.4 years. For boys, it was 72.0 years and for girls, 78.8 years. On the other hand, the infant mortality rate continued downward when a new benchmark was achieved--an all-time low, 8.9 per 1,000 live births. Also encouraging was a marked improvement in longevity among black Americans that significantly narrowed the white-nonwhite differential. PMID- 1411912 TI - Anti-arthritic medication usage: United States, 1991. AB - In 1991, about 70.3 million prescriptions for nonsteroidal anti-inflammatory drugs (NSAIDs) were filled across the United States to treat arthritis and related musculoskeletal problems. The retail costs exceeded $2.2 billion in 1991 and were 6 percent higher than the costs in 1990 despite a 2.2 percent decrease in volume of prescriptions written. Per capita consumption averaged 278.6 prescriptions per 1,000 population with substantial variation by state. Kentucky led with 380.9 per 1,000 population and the District of Columbia had the lowest rate, 177.0. Ibuprofens were the most frequently prescribed class of NSAIDs, with Motrin capturing 20 percent of this generic class. Naproxen (Naprosyn) was the second most frequently prescribed class accounting for 19 percent of the NSAIDs. PMID- 1411913 TI - A better definition of "accident mortality". PMID- 1411914 TI - [Athletic capacity after surgical management of acromioclavicular joint separation]. AB - Acromioclavicular separation is a common injury in sports. This study was done to show the activity and problems of athletes after operative treatment of this kind of injury. Between 1986 and 1989 21 athletes with acromioclavicular separation had been treated by operation. The coracoclavicular ligaments had been sutured and augmented by a PDS cord. The acromioclavicular ligaments had also been reattached and the ac-joint had been transfixed with a Kirschner-wire. The results show 18 athletes doing their sports on the same level as preoperatively. Two athletes with a frequency of sporting activity once a week could not continue their sporting activity. One athlete changed the disciplines to less shoulder stressing kind of sport. The comparison of clinical and radiological results showed no correlation, even patients with an osteoarthrosis of the ac-joint and coracoclavicular ossifications had best clinical results. We recommend therefore operative treatment for acromioclavicular separation in athletes. PMID- 1411915 TI - [Nuclear magnetic resonance tomography diagnosis of changes in the glenoid process in patients with unstable shoulder joints]. AB - In 4 fresh specimens and in 14 healthy volunteers we studied normal anatomy of the glenoid labrum by MRI. In a total of 124 patients we examined the shoulder joints by MRI. 69 patients had any kind of subacromial pathology. 55 patients showed a glenohumeral instability. All MRI findings were compared with the surgical findings during arthroscopy and during open surgery. 44 patients showed a recurrent anterior instability, 7 patients showed a multidirectional instability, 2 patients showed a posterior instability, and 2 patients presented acute anterior dislocation. We found significant variability in the labral shape as well as significant variability of anterior capsular attachment. The pathologic changes of the glenoid labrum were classified in four different types. In 78% we found a concomitant Hill-Sachs lesion of various diameter. 5 patients suffered from an additional complete rotator cuff tear. Compared to the intraoperative findings MRI had a sensitivity of 95%, a specificity of 94%, an accuracy of 94%, a positive predictive value of 91%, and a negative predictive value of 96% in detecting labral pathology. CLINICAL RELEVANCE: Presenting a high diagnostic value for detecting Bankart lesions, MRI may replace other diagnostic modalities like CT-arthrography. PMID- 1411916 TI - [Monteggia injuries in athletes. Causes, classification, results]. AB - Monteggia-fractures are serious combination injuries to the forearm. Sport injuries are being increasingly observed; the reason for this, besides the general expansion of mass sports, is the increasing burden of high-performance sports. Monteggia fractures can occur during a fall on an outstretched arm, for example in motor or bicycle sport injuries, but also when falling from gymnastic equipment. Generally, it is easy to diagnose the monteggia injury. Considerable secondary damage could occur from the frequent failure to notice the involved radiohumeral joint. It should be demanded that in case of an uluar fracture the adjoining joints should be x-rayed on two planes in order not to overlook the possibility of a chisel fracture. The different forms of this combination injury, its classification and the results of our own medical bulletins are presented. PMID- 1411917 TI - [Isolated injuries of the pulley of the finger flexor tendon sheath--injuries in extreme climbing sports]. AB - Injuries of pulleys are quite common in mountain climbing. The clinically diagnosed rupture of a pulley can now be verified by MRI. Partial ruptures, which in MRI always showed as scars, can frequently lead to intrinsic bow-stringing. The injuries were primarily treated non-surgically. With regard to chronic, recurring cases or large ruptures, however, annular ligament plastics have to be considered. As a prophylaxis we recommend special training exercises for climbers on wide ledges with changing exertion patterns and a tape-bandage for the fingers. During climbing, the PIP-joint should best not be strained in an obtuse angle. Warming-up and stretching exercises before climbing are absolutely necessary. PMID- 1411918 TI - [Ultrasound image of the Lachman test in lesions of the anterior cruciate ligament]. AB - The sonographic examination of the knee-joint can, in many pathological alterations of the knee-joint, supply additional informations. In the standardized ultrasound examination of the knee-joint ventral and dorsal sectional planes will be adjusted (4, 7, 14, 17). For the examination of the lesions of the anterior cruciate ligament direct adjustment techniques in the aere of origin of the anterior cruciate ligament (15, 16) and indirect examination methods are known (7, 8, 9, 20). While Hien chose a direct medial parapatellaric horizontal sagittal sectional plane in the course of the lig. patellae (8), we carry out our examination in a ventral infrapatellaric sagittal plane. The examinations were conducted with an ultrasound unit of the type Siemens Sonoline SL 2 with a linear transducer with a frequency of 5 MHz without a stand off pad. In the course of a prospective clinical examination an anteromedial test of stability of both knee-joints was conducted on 360 patients with the help of a sonographic Lachman-test. Two examination groups were formed: in group 1 60 patients with a arthroscopically secured lesion of the anterior cruciate ligament were registered and set against 300 probationers with "empty" anamnesis of the knee-joint of group 2. In the group of patients with a cruciate ligament injury a tibia translation of 5.3 mm in the Lachman-test was found; the side difference between the leg injured and the one uninjured amounted to 3.0 mm. In the control group the tibia translation amounted to 2.9 mm with a side difference of 0.9 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1411919 TI - [Tarsal tunnel syndrome in athletes]. AB - Pain in the hindfoot due to overuse has many causes. One uncommon cause is the entrapment of the posterior tibial nerve: the tarsal tunnel syndrome. Pain when palpating posterior the medial malleolus and pain in the abductor hallucis muscle are typical symptoms. Application of a local anaesthetic leads to immediate pain relief. The distal motoric latency is prolonged, but not in all cases. First of all, treatment consists of local and oral antiphlogistics, orthopaedic arch support and physiotherapy. In case of therapy-resistant pain over more than three months period, surgical decompression of the tibial nerve should be performed. In the last three years we treated 18 patients with a tarsal tunnel syndrome: 6 of 8 patients were symptom-free after surgical intervention, whereas only 3 of 10 were symptom-free after conservative treatment. PMID- 1411920 TI - [Discussion of indications for surgical treatment of pediatric forearm shaft fractures]. PMID- 1411921 TI - [Traumatology and athletic injuries in basketball]. AB - This analysis outlines the facts concerning sports injuries and damages of 473 active basketball players covering a 5-year period in more than 100 clubs in southern Germany. The average age was 26.8 years and 34.5% were women. 658 medically treated basketball injuries were described in detail. With 40.7% distortions were the most frequent injuries followed by ruptures of ligaments in 24.6% and fractures in 9.3%. In the majority of cases the lower extremities were involved (65.3%), of which most commonly the ankle joint was injured (45.6%). Another 14% were lesions to the fingers and 12.9% trauma to the knee. In 3600 reported cases players did not consult a physician after inflicting distortions to a ankle or a finger. Aside from interaction with adversaries (41%) also the relatively heavy ball (650 g) caused 11.9% accidents. Survey shows, that younger players and "center"-players were most often subject to injuries. More than 2/3 of actives in question suffer from permanent pain due to basketball activities. 43.8%, mainly younger players, report continues pain in the knee and 28.1%, predominantly older players, suffer from permanent damage of the ankle joint, caused by repeatedly occurring, however light, distortions of the ankle. PMID- 1411922 TI - [Radiochemotherapy concepts in advanced carcinomas of the mouth, oro- and hypopharynx]. AB - Among combined radiochemotherapy regimens of advanced head and neck tumors four modalities can be discriminated: 1. Induction chemotherapy, 2. simultaneous radiochemotherapy, 3. adjuvant chemotherapy, 4. accelerated hyperfractionated radiotherapy and chemotherapy. The results of the presently available randomized trials are as follows: 1. Induction chemotherapy has no influence on long-term recurrence-free survival. 2. With respect to simultaneous radiochemotherapy, recurrence-free survival has been unproved with 5-FU and Mitomycin C. 3. There is evidence that adjuvant cisplatin therapy improves recurrence-free survival. 4. No results are available to date using hyperfractionated accelerated radiotherapy regimens in combination with chemotherapy. PMID- 1411923 TI - Unusual combination of Cis platinum and radiotherapy followed by a three fractions per day irradiation in splitcourse: a phase I-II study in brain glioma patients. AB - An unusual protocol based on a preliminary clinical study on cylindromas metastasized to the lung was proposed to brain glioma patients: Day 2 100 mg/m2 i.v. Cis platinum (Cis PII) followed at days 3 and 5 by 6 Gy irradiation (RT) in two fractions and three days. Five cycles were scheduled at 21 days interval. On disease progression a three fractions per day radiotherapy regimen (3 FRT) in split-course (two series of 22.50 Gy in 15 fractions and five days separated by a two weeks period of rest) was then delivered to the patients. All patients had a measurable mass on the CT scan. 19 were entered into the study: 13 as first line therapy (group A) and six for salvage treatment (group B). Tolerance was globally good. Eight patients were considered responders at the end of five cycles of Cis PII-RT. They were all group A patients. Median symptom-free interval was six months for the whole population. Survival was twelve months. The 3 FRT was well tolerated but does not seem to have improved the therapeutic gain of the chemoradiotherapy combination. The present study concerns patients whose prognosis was poor on inclusion: surgery inadvisable or unsatisfactory and diagnosis mainly based on biopsy only. The number and the duration of responses justify further study into Cis PII as first line therapy as either an effective cytotoxic drug or a potential radio enhancer. PMID- 1411924 TI - Long-term follow-up in 39 patients with an ependymoma after surgery and irradiation. AB - 1954 to 1989, 33 patients with intracranial ependymomas had primary treatment in our hospital with surgery and postoperative radiotherapy. Five- and ten-year survival rates were 48% and 34% in 25 patients with a high-grade ependymoma and for low-grade ependymomas was maintained at 78% for both the five- and ten-year follow-up period. Cumulative frequency of local or intracranial recurrence was 70% (high-grade) and 20% (low-grade). Despite the fact, that only three of 25 patients with high-grade ependymomas had spinal irradiation with 19.5 to 30 Gy, there was only a single patient with clinical signs of spinal metastases simultaneously with an intracranial recurrence. Twelve out of 13 living patients without signs of tumor have been classified according to the neurological performance: Performance was good or very good in five patients, satisfying in three with an independent life, fair in two patients working in a sheltered office and dependent on some assistance and poor in two patients. Published results are discussed and compared with the own observations and our current treatment policy is given. PMID- 1411925 TI - [Transrectal sonographic (TRUS) prostatic volumetry in assessing tumor response to radiation]. AB - The aim of this study was to document the grading-related response of carcinoma of the prostate to radiotherapy, especially in views of the fact that the PSA values of hormonal therapy are not evaluable if hormonal therapy is done prior to radiotherapy or in patients with high likelihood of metastatic spread. Controls were done on 55 patients before, during and after primary external radiotherapy of carcinoma of the prostate with volumetric analysis of transrectal ultrasound (TRUS) of the prostate. There were significant differences between G1 and G2 tumors on the one hand and G3 tumors on the other hand. The latter had a much larger volume to start with and their volume reduced more rapidly after therapy. PMID- 1411926 TI - [The value of adjuvant irradiation in lymphatic vessel invasion in patients with a cervical carcinoma in histopathological stage Ib and with negative lymph nodes]. AB - The present retrospective study attempts to evaluate the significance of adjuvant radiotherapy as a prognostic factor for stage Ib cervical carcinoma without lymph node metastases but with lymph-vascular space invasion. 54 patients fulfilled the inclusion criteria: histopathological stage Ib, radical hysterectomy with pelvic lymphadenectomy, negative pelvic lymph nodes and lymph-vascular space involvement. Though larger tumors were found (tumor infiltration of the cervix greater than 2/3) in the irradiated group (chi 2-test p = 0.003), there was no significant difference in the five-year overall survival (92% five-year survival without vs. 90% with adjuvant irradiation). In contrast statistical significant difference was found in recurrence-free interval between these groups (Wilcoxon test p = 0.02). PMID- 1411927 TI - [Pseudotumor orbitae--a chameleon in diagnosis and therapy?]. AB - Between 1972 and 1988, 25 patients were diagnosed and treated for "pseudotumor orbitae" in the Departments of Radiotherapy and Ophthalmology of Munster University Clinics. All cases had been initially confirmed by histology. Later in seven cases (28%) the histology showed a definitive alteration, and eventually turned to malignancy in five patients. Criteria indicating such a shift are seen in higher age, subacute onset of the disease, low pain, minor signs of inflammation, low echoes in ultrasound diagnostics, and the absence of "Dutcher bodies" in histiocytes, if these are evident in histology. These patients at increased risk of malignant transformation should be considered for radiotherapy at an earlier stage than prescribed by the current routine. PMID- 1411928 TI - [Case reports on the importance of the locoregional radiotherapy of Merkel cell tumor]. AB - The Merkel cell tumor is becoming an increasingly diagnosed primary neoplasm of the skin. This subepidermal tumor is commonly located on the head and neck or extremities of elderly patients. Occasionally misinterpreted as cutaneous metastases, they show a high rate of local recurrence (27 to 52%) and distant metastatic spread (18 to 52%). The definitive diagnosis can be made with immunohistochemistry. Wide surgical excision with postoperative irradiation to the local site and regional lymphatics is the therapy of choice. In seven patients we describe management strategies and discuss their clinical results. PMID- 1411929 TI - [The special aspects in the planning and use of an electron linear accelerator facility for intraoperative radiotherapy (IORT)]. AB - Limiting conditions for the planning of the installation of an electron linear accelerator in an operating theatre are described taking into account the radiotherapeutical and surgical requirements based on the example of the Essen facility for intraoperative radiotherapy (IORT) with electrons. Special features of the facility like a non-contact electron applicator system with television monitoring, table-top trolley, which is used also during irradiation, are explained in detail. Measured isodose curves for all tubes and all electron energies serve for the radiotherapist as criteria for decision on tube size and electron energy selection during surgical operation. The influence of misalignments of the tube on dose distributions is investigated. Limit values of alignment tolerances are deduced. Daily constancy tests for monitor calibration, electron energy, and tube alignment system are to be performed for quality assurance. Tables of the planned and realized treatments and of a representative time schedule of an IORT give a survey on the indications and the necessary time effort and staff. Completion of the set of tubes as well as optimization of the tube fixation accessory and of the table-top trolley are main subjects for future developments. PMID- 1411930 TI - Responsibilities and rights. PMID- 1411931 TI - Primary colorectal anastomosis with the intracolonic bypass tube. AB - BACKGROUND: Intracolonic bypass with primary colocolonic or colorectal anastomosis may be an effective option in the operative management of complicated colonic disease when adequate bowel preparation is not possible. A pliable latex tube is anchored to mucosa and submucosa 3 centimeters proximal to a site of colocolonic anastomosis and later spontaneously evacuated by way of the rectum. METHODS: Twenty-nine consecutive patents who required urgent colorectal operations in the presence of unprepared bowel underwent left colon resection with intracolonic bypass and primary anastomosis. These patients would have otherwise undergone multistage procedures for the management of the colorectal disorders. Demographic data, APACHE II scores, and type and frequency of complications were recorded. RESULTS: Between July 1, 1990, and June 30, 1991, 31 patients were eligible for entry in the study. Two patients ultimately had contraindications for the use of intracolonic bypass. The causes encountered included complicated diverticular disease, colonic carcinoma, sigmoid volvulus, and iatrogenic colorectal injury. Complications included wound infection (7), myocardial infarction (2), prolonged ileus (1), deep vein thrombosis (2), and anastomotic leak (2). Postoperative myocardial infarction and subsequent multiorgan system failure were responsible for the only death in this study. CONCLUSIONS: Intracolonic bypass permits a safe primary anastomosis where multistage procedures would otherwise be required. Avoidance of colostomy and the attendant socioeconomic benefits warrants further study of this method. PMID- 1411932 TI - Radioimmunoguided surgery challenges traditional decision making in patients with primary colorectal cancer. AB - BACKGROUND: Initial experience with the radioimmunoguided surgery system (RIGS) has been found to impact on decision making in patients with recurrent colorectal cancers. Reported here is experience with RIGS-influenced therapeutic decisions in patients with primary colorectal cancer. METHODS: Thirty-six evaluable patients with primary cancers were injected with the second-generation anti-tumor associated glycoprotein antibody CC49 labeled with 1 to 2 mCi iodine 125. Pharmacokinetic determination and precordial counts were obtained after injection and weekly until levels were less than 20 counts/2 sec. At surgery abdominal and pelvic explorations were performed, first traditionally by inspection and palpation and then with the hand-held, gamma-detecting probe. RIGS-positive tissue was considered cancerous and removed if possible. RESULTS: Thirty patients (83%) had positive antibody localization at surgery. Of those patients with localization, in 24 (80%) additional information was obtained at the time of surgery. In 11 patients (34%) staging changes were made as a result of RIGS exploration. New findings resulted in operative changes in nine patients (25%). Eleven (30%) of the original 36 patients became eligible for adjuvant chemotherapy based on current recommendations because of RIGS findings. CONCLUSIONS: In conclusion, the RIGS system provides immediate staging information that impacts on therapeutic interventions, challenging the adequacy of traditional procedures alone for primary colorectal cancer exploration. PMID- 1411933 TI - Total parenteral nutrition-induced changes in gut mucosal function: atrophy alone is not the issue. AB - BACKGROUND: Total parenteral nutrition (TPN) has been implicated in gut atrophy and breakdown of barrier function leading to bacterial translocation (BT) in animals. BT during TPN, however, is not found consistently, and it has therefore been suggested that macromolecular permeability may occur independently of BT during TPN. METHODS: Male Sprague-Dawley rats were administered isocaloric standard TPN enterally, parenterally, or split equally between the two routes or allowed food ad lib. A second group of rats was administered isocaloric TPN with and without 4% lipids, and changes in gut barrier function were assessed by measuring lactulose permeability. RESULTS: Rats receiving TPN both enterally and parenterally maintained histologic intestinal structure to the same degree as rats fed enterally and those allowed food. Although parenteral feeding led to significant gut atrophy and cecal bacterial overgrowth, BT was not increased. Gut permeability to lactulose, however, was increased significantly in the TPN groups. Lipid content did not affect outcome. CONCLUSIONS: These results suggest that gut atrophy, BT, and permeability to macromolecules are not necessarily related. Gut-origin septic states during TPN or trauma may be caused by an increased escape of macromolecules from the gut, and BT may be an end result rather than a primary cause of such septic episodes. PMID- 1411934 TI - Comparison of minimally invasive methods of parietal cell vagotomy in a porcine model. AB - BACKGROUND: Parietal cell vagotomy (PCV) is an accepted therapy for peptic ulcer disease. Traditional operative PCV results may be obtained laparoscopically or endoscopically. The purpose of this study was to quantitatively evaluate newer methods of PCV. METHODS: Variations in PCV, gastroscopic chemoneurolysis and laparoscopic photoneurolysis, were evaluated in 20 to 25 kg pigs. Traditional operative PCV was performed by laparotomy and served as the operative control. With a posterior truncal vagotomy, a PCV was performed laparoscopically by an anterior seromyotomy with either operative division of the neurovascular bundles with titanium clips or with a defocused CO2 laser. Transesophageal gastroscopic PCV was performed by transmucosal injections of the chemoneurolytic agents, 0.75% cobaltous chloride or 0.1% benzalkonium chloride. Adequacy of PCV at the time of operation was assessed by endoscopic Congo red testing. Two weeks later, repeat Congo red testing was performed by open gastrotomy. Quantitation of completeness of PCV and statistical comparison was determined by photographing the pentagastrin-stimulated gastric mucosa 5 minutes after Congo red application and subsequent comparison of innervated area versus total gastric mucosal area by a computer-driven digitized area-calculation program. RESULTS: All PCV techniques studied produced significant acid-secretory reduction, and both laparoscopic and gastroscopic PCV denervated the parietal cells in a manner comparable with operative PCV. Laser photoneurolysis could only be accomplished by producing full thickness necrosis of the gastric wall. Submucosal injection of cobaltous chloride produced granulomatous nodules with foreign body crystals. Unlike operative and laparoscopic PCV, transmucosal gastroscopic benzalkonium PCV did not produce gross gastroparesis. CONCLUSIONS: All evaluated laparoscopic and endoscopic PCV techniques effectively denervated the parietal cells of the porcine stomach when evaluated at 2 weeks after treatment. Gastroscopic submucosal injection of benzalkonium chloride produced effective denervation with no evident histologic tissue changes and suggestive evidence of normal gastric emptying. Further evaluation with more extended periods of observation of these new techniques of performing PCV appear warranted. PMID- 1411935 TI - Natural history of recurrent and residual stenosis after carotid endarterectomy: implications for postoperative surveillance and surgical management. AB - BACKGROUND: Noninvasive surveillance of patients after carotid endarterectomy is practiced routinely to detect recurrent stenoses. Many authors advocate repair of asymptomatic severe stenoses so detected. The likelihood of these lesions causing neurologic symptoms is unknown. Our aims were to (1) define the incidence of lesions, (2) determine the frequency of associated neurologic symptoms, and (3) identify patient-dependent factors that might predict restenosis. METHODS: Data on the status of 449 carotid arteries after endarterectomy were reviewed. The number of recurrent and residual severe (greater than or equal to 80%) stenoses was identified. Interval to development of symptoms was determined by life-table analysis. Patient-dependent factors (age, gender, smoking, diabetes, and patch closure) were evaluated by univariate and multivariate analysis to identify possible associations with severe lesions. RESULTS: Severe (greater than or equal to 80%) stenoses were seen in 35 patients (7.9%). Residual lesions were seen in 17 cases (eight occlusions and nine stenoses); recurrent lesions were identified in 18 patients (3.9%). Symptoms developed in five cases (14%) (one residual and four recurrent) 35, 48, 68, 98, and 103 months after surgery. The likelihood of developing symptoms associated with stenosis at 5 years was 6%. No factors correlated with residual stenosis. Age less than 60 years, female gender, primary closure, and absence of diabetes were more common in patients with recurrent lesions. CONCLUSIONS: Severe lesions can be found after carotid endarterectomy in at least 8% of patients and consist of residual defects, as well as recurrent stenoses. Recurrent lesions are more common in specific patient subgroups. These lesions are stable for long periods and the majority remain asymptomatic. Operation is not indicated unless symptoms develop in these patients. Intraoperative completion evaluation may be indicated to reduce the incidence of residual disease. Early noninvasive evaluation is useful as a quality-control measure. Repeated surveillance may provide data on the course of restenosis or contralateral disease progression but is of limited clinical benefit. PMID- 1411936 TI - A preliminary experience with use of magnetic resonance angiography in assessment of failing lower extremity bypass grafts. AB - BACKGROUND: This study evaluates the ability of magnetic resonance angiography (MRA) to detect hemodynamic failure of lower extremity bypass grafts and questions whether conventional angiography is necessary for this purpose. METHODS: A prospective surveillance protocol with segmental plethysmography and color flow Doppler scanning has been used to detect hemodynamic graft failure in 110 patients with 120 lower extremity bypass grafts (90 vein, 30 polytetrafluoroethylene). Twenty (17%) bypass grafts fit the criteria for impending failure (drop in ankle/brachial index determination greater than or equal to 0.15; velocity less than 45 cm/sec; focal velocity two to three times mean graft flow). Intraarterial digital subtraction angiography and MRA studies were performed on all 20 grafts. RESULTS: Intraarterial digital subtraction angiograms showed graft occlusion in two grafts, severe native artery progression in three grafts, graft wall defects in six grafts, and anastomotic strictures in nine grafts. MRA results showed an exact correlation in 15 (75%) of 20 cases. False-positive tests occurred in four cases (20%), and false-negative tests occurred in one case (5%). Common reasons for interpretation error were metallic clips and field-of-view limitations. These problems are preventable. When MRA results were compared with color flow scan data, overall accuracy improved to 95%. CONCLUSIONS: Our studies suggest that MRA can be useful in graft surveillance and that the need for conventional angiography may be reduced in the future. PMID- 1411937 TI - Internal carotid artery occlusion: operative risks and long-term stroke rates after contralateral carotid endarterectomy. AB - BACKGROUND: To determine the short- and long-term benefits of carotid endarterectomy (CEA) contralateral to an occluded internal carotid (ICA), we reviewed our experience since 1976. METHODS: In 66 (13.8%) of 478 patients undergoing 544 CEAs, the contralateral ICA was occluded. Mean follow-up was 50.1 months (range, 1 to 165 months). Complete follow-up was available in 83.0% of patients. RESULTS: Operative death occurred in one (1.5%) of 66 patients with contralateral occlusion and six (1.3%) of 478 patients without contralateral occlusion (p = 0.99). Operative strokes occurred in two (3.0%) of 66 patients with contralateral occlusion and 14 (2.9%) of 478 without contralateral occlusion (p = 0.99). Life-table stroke-free rates at 1, 3, 5, and 8 years were 96.8%, 93.0%, and 93.0% in patients with contralateral occlusion and 95.9%, 94.2%, 91.1%, and 88.0% in patients without contralateral occlusion (p = 0.36). Five- and 8-year stroke-free rates were 100% and 100% in the asymptomatic subgroup with occlusion, 95.9% and 92.2% in the asymptomatic subgroup without occlusion (p = 0.45), 91.2% and 91.2% in the symptomatic subgroup with occlusion, and 89.7% and 86.8% in the symptomatic subgroup without occlusion (p = 0.47). Life-table survival rates at 5 and 8 years were 72.5% and 56.0% in patients with contralateral occlusion and 81.8% and 69.0% in patients without contralateral occlusion (p = 0.15). CONCLUSIONS: CEA performed in patients with and without symptoms with a contralateral ICA occlusion produces short- and long-term mortality and stroke morbidity rates comparable to those of similar patients without contralateral ICA occlusion. The indications for CEA in patients with contralateral ICA occlusion should not differ from those applied to patients without contralateral occlusion. PMID- 1411938 TI - Management of myasthenia gravis by extended thymectomy with anterior mediastinal dissection. AB - BACKGROUND: Thymectomy has continued to gain acceptance as definitive treatment for myasthenia gravis. Because of the nature of thymic embryology with scattered rests throughout the anterior mediastinum, we advocate a transsternal thymectomy with extended anterior mediastinal dissection. METHODS: A series of 48 patients with myasthenia gravis treated by thymectomy between 1979 and 1991 were reviewed. RESULTS: The mean length of duration of disease from onset to operation was 48.7 +/- 11.3 months, and the mean length of follow-up was 51.6 +/- 6.5 months. The operation was associated with a 21% morbidity rate (4% major morbidity) with no deaths. Forty-five patients (94%) have improved, requiring decreased medication. The overall drug-free remission rate was 42%. Of the 20 patients in remission, three had thymomas and four had hyperplastic glands. All of the patients who achieved drug-free remission were classified as Osserman's I or II. CONCLUSIONS: An aggressive surgical approach to myasthenia gravis can result in a high percentage of overall improvements and drug-free remissions. The best results are achieved in patients with lower-stage disease. Therefore transsternal extended thymectomy for myasthenia gravis appears to be the procedure of choice and should be advocated as soon as the diagnosis is made and the patient stabilized. PMID- 1411939 TI - Long-term follow-up of patients with node-negative breast cancer treated only by regional therapy. AB - BACKGROUND: This study examines the potential impact of intercurrent diseases on survival after adjuvant chemotherapy for node-negative (N0) breast cancer in light of 30-year follow-up results in 136 patients with N0 disease receiving only regional therapy at the University of Texas M.D. Anderson Cancer Center between 1958 and 1960. METHODS: We made a retrospective review of treatment records. RESULTS: Thirty-nine women (28.6%) died of the initial breast cancer, including 12 (22%) of 54 premenopausal women, 15 (43%) of 35 perimenopausal women, and 12 (25%) of 47 postmenopausal women (p less than or equal to 0.09). Six (12%) of 49 patients with T1 disease died of the initial breast cancer versus 27 (38%) of 70 patients with T2 disease and 6 (35%) of 17 patients with T3 disease (p less than or equal to 0.006). Five of 10 women died of metachronous contralateral breast primary lesions. Deaths from other cancers occurred in 11%, 2.8%, and 6.4% of premenopausal, perimenopausal, and postmenopausal women, respectively. Deaths from nonmalignant conditions occurred in 22%, 20%, and 59% of premenopausal, perimenopausal, and postmenopausal women, respectively. Overall survival at 30 years was 35 (26%) of 136 patients. CONCLUSIONS: Given these statistics, if one postulates that adjuvant chemotherapy reduces the death rate from an initial breast cancer by 30% to 77% (estimates based on data from adjuvant chemotherapy trials in patients with N+ or N0 disease), a 5% to 12.9% increase in the 30-year survival would have resulted. PMID- 1411940 TI - Liver transplantation for alcoholic liver disease. AB - BACKGROUND: Alcoholism is the leading cause of end-stage liver failure in the United States, but the application of liver transplantation to the treatment of alcoholic liver disease remains controversial because of medical and ethical concerns. Information about the outcome of patients who undergo transplantation for alcoholic cirrhosis would help to resolve these concerns. METHODS: The results of 41 patients (Group 1) with alcoholic liver disease were compared with those of patients who underwent liver transplantation for other medical problems (group 2) at this center. Thirty of the 32 survivors from group 1 and 30 matched subjects from group 2 were interviewed to assess substance dependence, recidivism, and activity level. RESULTS: Compared with control subjects, patients with alcoholic liver disease had equivalent patient and graft survival rates and achieved an equal level of postoperative health. These results were achieved even though patients with alcoholic liver disease had significantly worse liver failure and more morbidity before surgery, and one third of the patients in this group were not abstinent before transplantation. CONCLUSIONS: We conclude that patients with alcoholic liver disease merit equal consideration for liver transplantation compared with other causes of liver failure. Treatment of the addictive disorder should be included before and after surgery. PMID- 1411941 TI - Preoperative risk factor assessment in liver transplantation. AB - BACKGROUND: Despite the increasing success of liver transplantation, there is lack of objective data defining appropriate candidate suitability. This study was undertaken to determine preoperative risk factors that independently or in combination affected outcome after orthotopic liver transplantation. METHODS: We reviewed data on 229 consecutive adult liver transplant recipients. Thirty-one preoperative risk factors recorded at the time of listing and immediately before transplantation were analyzed. Outcome variables included hospital mortality rates, bacterial or fungal sepsis, and the need for renal support. RESULTS: The overall hospital mortality rate was 15.7%. Patients who were in the intensive care unit immediately before transplantation had the highest hospital mortality rate (32.6%; p = 0.006), incidence of bacterial sepsis (51%; p = 0.001), fungal infection rate (27.6%; p = 0.001), and need for renal support (38.7%; p = 0.001). Preoperative renal dysfunction was significantly associated with sepsis and was reflected in higher hospital mortality rates (29.5%; p = 0.011). Child-Pugh class C was associated with higher mortality rates (23.9%; p = 0.017), an increased incidence of bacterial (37.2%; p = 0.020) and fungal infection (20.3%; p = 0.049), and a 30.4% requirement for postoperative renal support (p = 0.004). CONCLUSIONS: These results emphasize the need for earlier referral and transplantation in patients with advanced liver disease. Further studies are needed to refine identified risk profiles and devise strategies to decrease morbidity and mortality rates. PMID- 1411942 TI - The role of intrahepatic cholangiojejunostomy in liver transplant recipients after extensive destruction of the extrahepatic biliary system. AB - BACKGROUND: Extensive destruction of the extrahepatic biliary system after liver transplantation can be a catastrophic event. We present our experience with the use of intrahepatic cholangiojejunostomy (IHCJ) in this setting. METHODS: From July 1985 through December 1991, 668 liver transplantations were performed in 583 patients. Seven patients required IHCJ. This technique involves creating an anastomosis between the jejunal mucosal and hepatic parenchyma/capsule with the use of a Roux-en-Y limb of bowel. There were four adults and three children. The clinical presentation included bile leak (n = 4), subhepatic abscess (n = 2), and intrahepatic abscess (n = 1). The probable cause of these events included hepatic arterial thrombosis (n = 4), occult bile leak (n = 2), and fungal cholangitis (n = 1). RESULTS: After IHCJ, six of the seven patients are currently alive, with a mean follow-up of 28 months. The current liver function test results include a mean bilirubin of 0.7 mg/dl (range, 0.4 to 1.9 mg/dl), serum glutamic pyruvic transaminase of 69 units/L (range, 32 to 118 units/L), and gamma glutamyltranspeptidase of 118 IU/L (range, 111 to 265 IU/L). CONCLUSIONS: These results suggest that IHCJ is a safe and effective alternative to retransplantation in liver recipients with extensive destruction of the extrahepatic biliary system. PMID- 1411943 TI - Cause and management of upper gastrointestinal bleeding after distal splenorenal shunt. AB - BACKGROUND: The aims of this study were to determine the causes of recurrent upper gastrointestinal hemorrhage (UGH) after distal splenorenal shunting (DSRS) and to summarize our experience in the prevention and management of this complication. METHODS: This study is based on a retrospective review of 145 consecutive patients undergoing DSRS from 1978 through 1991. RESULTS: Recurrent UGH developed in 19 patients (13%), most frequently secondary to residual portal hypertension (84%). Eight patients had shunt thrombosis and 11 had patent shunts. The incidence of shunt thrombosis was significantly greater in patients whose splenic vein was less than or equal to 8 mm in diameter (44%) than those whose splenic vein was greater than 8 mm (7%, p less than 0.001). The frequency of shunt failure from 1985 through 1991 was significantly lower (2%) than from 1978 through 1984 (10%, p less than 0.05). Five patients, all with occluded shunts, underwent surgical treatment for recurrent UGH and three died (60%). Fourteen patients were managed nonoperatively, with a mortality rate of 38%. CONCLUSIONS: Recurrent UGH after DSRS occurs in patients with patent shunts and in those with occluded shunts; DSRS thrombosis is more frequent when the splenic vein diameter is less than or equal to 8 mm; DSRS thrombosis decreases with operative experience; and the mortality rate for this complication is high with both operative and nonoperative management. PMID- 1411945 TI - Necessity and safety of completion thyroidectomy for differentiated thyroid carcinoma. AB - BACKGROUND: The diagnosis of thyroid carcinoma during the course of lobectomy for a dominant nodule occasionally cannot be rendered on the basis of frozen section. Once the diagnosis of carcinoma is made, the question of completion thyroidectomy arises. The decision to perform completion thyroidectomy and the timing, safety, and efficacy of this procedure are reviewed. METHODS: During the past 25 years (1965 to 1990), we operated on 351 consecutive patients with thyroid carcinoma. One hundred of these patients (84 women and 16 men) were initially treated by unilateral thyroid lobectomy for the previously stated reasons. Histopathologic examination of the permanent sections of the initial thyroid lobectomy specimen demonstrated papillary carcinoma in 70 patients and follicular carcinoma in 30 patients. Within a few months, a completion thyroidectomy was performed. RESULTS: The completion thyroidectomy specimen contained papillary carcinoma in 33 (47%) of the 70 patients with papillary carcinoma and 10 (33%) of the 30 patients with follicular carcinoma. Overall, 43 of these 100 patients harbored thyroid carcinoma in the contralateral lobe. Complications of completion thyroidectomy were transient recurrent nerve paresis in two patients and temporary hypoparathyroidism in three patients, requiring calcium and vitamin D therapy for a few months. CONCLUSIONS: Although the significance and treatment of papillary carcinoma are debated on the basis of size and grade of the primary lesion and age and sex of the patients, once the diagnosis is made in one lobe we believe that a completion thyroidectomy should be considered, not only for papillary carcinomas but also for follicular carcinomas because 47% (papillary) to 33% (follicular) of these patients will harbor the neoplasm in the contralateral lobe. PMID- 1411944 TI - Familial nonmultiple endocrine neoplasia medullary thyroid carcinoma: an evolving clinical entity. AB - BACKGROUND: A rare kindred of familial nonmultiple endocrine neoplasia medullary thyroid carcinoma arising from a 73-year-old proband case is reported to further define this distinct entity. METHODS: Twenty-four family members across four generations, four with medullary thyroid carcinoma (MTC) and two with C-cell hyperplasia (CCH), were studied. RESULTS: Basal calcitonin levels were elevated in three patients with MTC and were normal in one patient with microscopic MTC and two patients with CCH who had persistent subtle elevation in calcium and/or pentagastrin-stimulated calcitonin levels. One patient had unilateral MTC without CCH. Associated abnormalities included papillary carcinoma (2), thyroiditis (4), adenoma (2), and colloid nodule (1). Minimum treatment was total thyroidectomy. Two patients with MTC and marked hypercalcitonemia have recurrent disease at 2.5 year and 11-year follow-up. Two patients with MTC and normal or minor elevations in basal calcitonin and two with CCH had normal provocative calcitonin testing at 6 to 18 months follow-up. CONCLUSIONS: Unilateral MTC without CCH and MTC in the elderly do not preclude a familial cause. Microscopic MTC or CCH may be seen with subtle elevations in stimulated calcitonin levels, and recognition allows for curative thyroidectomy. Other apparent dominant thyroid pathologic conditions may occur concomitantly with familial medullary thyroid carcinoma and thus routine calcitonin, and immunohistochemical testing should be performed in patients with an appropriate family history. PMID- 1411946 TI - Choledochal duct cyst: resection with physiologic reconstruction. AB - BACKGROUND: The accepted surgical treatment of choledochal duct cyst is complete excision and enteric drainage through an intestinal conduit. Peptic ulceration and fat malabsorption have been reported after Roux-en-Y reconstruction. Such long-term complications may be avoided by a technique that simulates normal physiology. METHODS: Twenty-one patients have undergone resection of a choledochal duct cyst in the past 12 1/2 years. The pathologic duct is resected to the level of normal mucosa. A short segment of jejunum with a intussusception valve (1.5 to 2 cm) is interposed between the common hepatic duct and the duodenum. The medical records and all radiographs of each patient were reviewed. Eighteen children were reexamined or the parents were contacted by phone. RESULTS: Twenty of 21 patients recovered without major perioperative complications. Twelve of them are well and have no symptoms at 3 to 12+ years (mean, 6 years) after operation. Four children are currently well 6 to 19 months after operation. Three children were well when lost to follow-up. Two patients have radiographic evidence of incompetence of the interposition valve. One of these, who initially underwent operation at 9 months of age, was reexplored at 10 months and at 10 years for a stricture at the hepaticojejunal anastomosis. The other, a 7-year-old girl who was admitted with jaundice and pancreatitis, has had episodic abdominal pain for 7 years after operation but is well. CONCLUSIONS: The valved jejunal interposition hepaticoduodenostomy offers superior biliary reconstruction after excision of a choledochal duct cyst. Normal physiology is simulated, with bile draining directly into the duodenum. A short conduit prevents stasis, and biliary reflux is minimized with the addition of an intussusception valve. PMID- 1411947 TI - Conservative management of large ovarian cysts in children: the value of serial pelvic ultrasonography. AB - BACKGROUND: The management of large ovarian cysts in children is controversial and complicated by a poorly understood natural history. The purpose of this study was to determine the course of sonographically detected large ovarian cysts in a pediatric population. METHODS: All pelvic ultrasonograms in which an ovarian cyst was detected during a 6-year period were reviewed. Large cysts were defined as those of more than 5 cm in any dimension or a volume of more than 13 cc. Clinical data and follow-up was derived from either the hospital chart or by telephone interview. RESULTS: Large ovarian cysts were detected in 92 of 191 patients (48.2%). The average age was 14.9 years (range, 3 to 22 years). Eight patients were premenarchal. In 23 patients, surgery was performed, with findings of neoplasm in 10. In patients managed without surgery and with follow-up, 46 of 51 cysts (90%) decreased in size or completely resolved. Both complex and simple cysts resolved. CONCLUSIONS: Most large ovarian cysts in children (simple or complex) may be safely followed with serial pelvic ultrasonography, because most cysts will either decrease in size or resolve. Neither the character of the cyst nor the size reliably predicted clinical outcome. The decision for surgical intervention should not be based solely on ultrasonographic characteristics, but other factors such as severe symptoms, complications associated with the large mass, other evidence suggestive of neoplasm, ovarian source in doubt, or whether the cyst fails to resolve or decrease in size on follow-up ultrasonography. PMID- 1411949 TI - Occult gastrointestinal malignancies producing metastatic Clostridium septicum infections in diabetic patients. AB - BACKGROUND: Clostridial soft-tissue infections usually occur from traumatic injury but may be related to unrecognized gastrointestinal malignancy. Overwhelming sepsis with Clostridium septicum developed in five diabetic patients within 24 hours of onset of disease, and their course is reviewed. METHODS: The personal experience of the author in four cases is reviewed. RESULTS: Patients were seen within 12 to 24 hours of the onset of the disease with painful, rapidly spreading, gas-producing infection of the lower extremity (three patients), upper extremity (one patient), or pelvis (one patient), with severe sepsis in four of five patients. Three of the five patients had pertinent past histories that should have led to the prevention of the disease. CONCLUSIONS: Urgent laparotomy should be performed in otherwise healthy diabetic patients who had rapidly progressive, necrotizing, gas-producing infections with no obvious source. Metastatic spread can recur if the focus is not eradicated. All diabetic patients with guaiac-positive stools should have a gastrointestinal evaluation, including colonoscopy if barium enema is normal. PMID- 1411948 TI - Pentoxifylline preserves small-intestine microvascular blood flow during bacteremia. AB - BACKGROUND: Intestinal mucosal ischemia with subsequent mucosal dysfunction has been implicated in the pathogenesis of ongoing sepsis and multiple systems organ failure. We have previously reported vasoconstriction and hypoperfusion in the intestinal microcirculation during sepsis. Efforts to improve microcirculatory blood flow during sepsis may lead to more effective treatment or prevention of multiple systems organ failure. Pentoxifylline improves survival and visceral organ perfusion in experimental sepsis and hemorrhage. The purpose of this study was to determine whether pentoxifylline would improve microvascular blood flow in the small intestine during bacteremia. METHODS: In vivo videomicroscopy was used to quantitate alterations of the small-intestine microcirculation during Escherichia coli bacteremia in rats pretreated with either intravenous pentoxifylline or saline solution. Systemic hemodynamic and microvascular variables were measured every 15 minutes for 2 hours. RESULTS: Tachycardia and increased cardiac output developed in bacteremic rats while they remained normotensive. Intestinal vasoconstriction and hypoperfusion occurred in bacteremic rats treated with saline solution. Microvessel diameters and blood flow remained within 5% to 10% of baseline in bacteremic rats pretreated with pentoxifylline. Pentoxifylline in nonbacteremic rats resulted in intestinal vasodilation and increased blood flow. CONCLUSIONS: Pentoxifylline prevented small-intestine vasoconstriction and preserved microvascular blood flow during hyperdynamic sepsis. Pentoxifylline in nonbacteremic rats increased microvascular blood flow. PMID- 1411950 TI - Hemorrhagic shock inhibits lipopolysaccharide-induced myelopoiesis in both germ free and conventional rats. AB - BACKGROUND: Bacterial translocation has been implicated in the alteration of the immune response after shock and trauma. This study examined the effect of bacterial translocation on myelopoiesis after hemorrhagic shock in germ-free and conventional rats. METHODS: Awake, unrestrained germ-free and conventional rats were bled to a mean arterial pressure of 30 mm Hg until the animal required infusion of 10% of the shed blood. Rats were resuscitated with shed blood and crystalloid. Sham rats were catheterized but not bled. Twenty-four hours after shock or sham, rats were administered lipopolysaccharide 100 micrograms or saline intraperitoneally. Twenty-four hours later, bone marrow cells were cultured for growth of granulocyte-macrophage colony-stimulating factor (CFU-GM). RESULTS: Lipopolysaccharide increased the number of CFU-GM/femur in sham germ-free rats (801 +/- 129 versus 455 +/- 110; p less than 0.05) and conventional rats (1458 +/ 200 versus 492 +/- 59; p less than 0.05) compared with saline-treated rats. In contrast, hemorrhagic shock inhibited lipopolysaccharide-induced CFU-GM growth in both germ-free and conventional rats. Shock, itself, was a stimulus for CFU-GM growth in germ-free but not conventional rats. Bone marrow white blood cell counts were unaffected by shock, lipopolysaccharide administration, or the germ free state. CONCLUSIONS: Hemorrhagic shock inhibited lipopolysaccharide-induced CFU-GM proliferation independent of the germ-bearing status of the rat, and bacterial translocation exerted no influence on myelopoietic dysfunction after hemorrhagic shock. PMID- 1411951 TI - Splenic abscess associated with endocarditis. AB - BACKGROUND: Refractory or recurrent sepsis in patients with endocarditis may be from splenic abscess. The purpose of this review is to assess this relationship. METHODS: Of 564 patients treated for documented endocarditis between 1970 and 1990, splenic abscesses developed in 27 patients. The mean age of the 18 men and nine women was 37 years. Etiologic factors included street drugs, dental abscess, and rheumatic fever. Symptoms included fever, myalgia, chills, and dyspnea; the prodrome averaged 2 weeks. Typical signs were heart murmur, left lower-lobe infiltrate, and leukocytosis. Splenomegaly was found in three patients. All patients had valve lesions, which involved the aortic valve alone in 10 patients, the mitral valve alone in eight patients, and multiple valves in nine patients. RESULTS: A splenic defect on computed axial tomographic scan was diagnosed correctly as an abscess in 10 patients, was indeterminant in three patients, and was incorrectly called an infarct in four patients. Thirteen patients died. All 10 patients treated without splenectomy died, including five patients who underwent valvular replacement. In contrast, only three of 17 patients treated by splenectomy with (11 patients) or without (six patients) valvular surgery died. CONCLUSIONS: Splenic abscess often accompanies endocarditis. The diagnosis is suspected by refractory fever and confirmed by abdominal computed axial tomography scan. Splenectomy is warranted before or after valvular surgery, depending on the patient's clinical response to antibiotics. PMID- 1411952 TI - Duration of antibiotic therapy for penetrating abdominal trauma: a prospective trial. AB - BACKGROUND: The optimal duration of antibiotic use in penetrating abdominal trauma is incompletely defined. It is generally accepted that short-term antibiotics are appropriate for low-risk wounds. However, with colon injury and significant degree of injury, abdominal trauma index (ATI) more than 25, concern exists that short-term treatment is not adequate. METHODS: The study was a prospective double-blind trial of 24-hour treatment (cefoxitin or cefotetan) compared with 5-day treatment in 515 patients. Major abdominal infections (MAI) included abscess, necrotizing fasciitis, and diffuse peritonitis. RESULTS: MAI occurred in 8% of those patients with 1-day therapy and 10% with 5-day therapy. Subgroup analysis of high-risk groups (colon wounds and ATI of more than 25) showed the following MAI rates: colon, 1-day therapy, 14%; 5-day therapy, 15%; ATI of more than 25, 1-day therapy, 17%; 5-day therapy, 30%. CONCLUSIONS: Regardless of contamination and degree of injury, 24-hour antibiotic therapy is satisfactory for all penetrating abdominal trauma. PMID- 1411953 TI - Clinical value of endoscopy and histology in the diagnosis of duodenogastric reflux disease. AB - BACKGROUND: The endoscopic observation of a bile lake in the stomach, antral gastritis, or ulcerations and the histologic finding of foveolar hyperplasia or chronic gastritis have been implicated as indicators of excessive duodenogastric reflux. The accuracy of these criteria was evaluated in 135 patients with nonspecific symptoms in the foregut suggestive of duodenogastric reflux and no evidence for alcohol- or drug-induced gastric mucosal injury. METHODS: The presence of excessive duodenogastric reflux was objectively determined by means of both gastric pH monitoring and cholescintigraphy with cholecystokinin stimulation. RESULTS: Endoscopy showed antral gastritis in 67 patients, gastric ulcers in 19, and a bile lake in the stomach in 39 (total of 135 patients). Of 90 patients who underwent biopsy, histologic findings showed foveolar hyperplasia in 26, chronic gastritis in 19, and active gastritis in 28 patients. The latter condition was associated with Helicobacter pylori in 20 patients. When gastric pH monitoring, cholescintigraphy, or both were used as "gold standard," the sensitivity, specificity, accuracy, and positive predictive value of endoscopic and histologic criteria to diagnose the presence of excessive duodenogastric reflux were poor except in the rare case of active gastritis but no Helicobacter pylori. CONCLUSIONS: The presence of duodenogastric reflux disease cannot be accurately diagnosed with endoscopic or histologic criteria. The diagnosis should be made with objective techniques, particularly when surgical therapy is considered. PMID- 1411954 TI - Use of the appendix for urethral reconstruction in children with congenital anomalies of the bladder. AB - BACKGROUND: The presence of the cecal appendix offers a unique opportunity for the achievement of urinary continence and stable access to the reconstructed urinary bladder. METHODS: We have reviewed the cases of 17 children treated over a 56-month period whose urinary anomalies have required the construction of a neourethra. Fourteen of these patients underwent neourethral reconstruction by use of the appendix. RESULTS: All neourethras are easily catheterized, and all are continent. CONCLUSIONS: The ease of application of this reconstructive modality along with its high success rate makes incidental appendectomy contraindicated in children with congenital anomalies of the bladder. PMID- 1411955 TI - Preoperative screening with ultrasonography for laparoscopic cholecystectomy: an alternative to routine intraoperative cholangiography. AB - BACKGROUND: Laparoscopic management of choledocholithiasis is not routinely successful. A prospective study was undertaken to determine if preoperative screening with ultrasonography and liver function tests (LFTs) could minimize the incidence of unsuspected choledocholithiasis. METHODS: One hundred twenty-one patients were studied. Patients with a common bile duct greater than 6 mm and either clinical symptoms or elevated LFT results were referred for preoperative endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Ten patients (8%) were referred for preoperative ERCP, of whom seven had choledocholithiasis, two had papillary stenosis, and one had a normal examination (90% positive ERCPs). One hundred eight patients underwent successful laparoscopic cholecystectomy. Nine patients underwent postoperative ERCP dictated by increasing common bile duct size, elevated enzyme levels, or symptoms. Four patients (3%) had choledocholithiasis that was successfully treated endoscopically. One patient had papillary stenosis, one had oriental cholangitis, and three had normal results on examination. CONCLUSIONS: In this study ultrasonography and LFTs identified patients at high risk for choledocholithiasis, allowing preoperative referral for endoscopic stone extraction. PMID- 1411956 TI - Laparoscopy: the preferred method of cholecystectomy in the morbidly obese. AB - BACKGROUND: Morbid obesity has been considered a contraindication to laparoscopic cholecystectomy (LC). METHODS: To evaluate this we reviewed our first 201 patients undergoing LC and compared the operative procedure and outcome in morbidly obese (greater than or equal to 100 pounds over ideal body weight [IBW]) and nonobese patients. We also compared a group of morbidly obese patients who underwent standard open cholecystectomy (n = 11) with the obese group undergoing LC (n = 21). All groups were comparable in terms of age, sex, and symptoms (acute vs chronic). The obese groups undergoing LC and open cholecystectomy had similar weights (134.0 +/- 9.4 pounds over IBW [range, 100 to 286 pounds] and 133.8 +/- 6.0 pounds over IBW [range, 108 to 170 pounds], respectively) and were significantly different from the nonobese group undergoing LC (28.3 +/- 2.0 pounds over IBW [range, 23 to 98 pounds]). Parameters evaluated included operative time, resumption of normal diet, length of postoperative hospitalization, complications, conversion to open procedure, and ability to perform cholangiography. RESULTS: There were no statistically significant differences between the obese and nonobese groups undergoing LC in any parameters studied (operative time, 151.7 +/- 4.0 minutes vs 160.7 +/- 9.9 minutes; tolerance of diet, 1.2 +/- 0.1 days vs 1.1 +/- 0.1 days; time to discharge, 2.0 +/- 0.1 days vs 1.8 +/- 0.2 days; complications, 7.0% vs 0.0%). Operative time (117.6 +/- 11.6 minutes) was shorter (p = 0.45) in obese patients undergoing open cholecystectomy. However, time to normal diet and length of postoperative hospitalization were significantly longer (3.1 and 4.6 days, respectively; p less than 0.01), and there were more complications (18.2%). CONCLUSIONS: Rather than being contraindicated in the morbidly obese, LC appears to be the preferred method of cholecystectomy. PMID- 1411957 TI - Secondary pancreatic infections: are they distinct clinical entities? AB - BACKGROUND: Infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have been proposed as distinct clinical entities in terms of treatment and outcome. To evaluate this classification, we reviewed the clinical course and bacteriologic findings of pancreatic infections. METHODS: Of 1299 patients with pancreatitis or a related complication admitted over a 7-year period, 64 (4.9%) with culture-documented secondary pancreatic infections were reviewed with regard to cause, clinical course, bacteriologic findings, and outcomes. RESULTS: Group I consisted of 23 patients with infected pseudocysts; group II, 20 patients with pancreatic abscesses; and group III, 21 patients with infected pancreatic necrosis. The causes were alcohol in 36%, biliary tract disease in 30%, and postoperative in 16%, with no significant difference between groups. Patients in group I had abdominal pain or a mass without accompanying signs of sepsis, whereas patients in groups II and III had sepsis. In group I, 15 patients were treated with internal drainage, four with percutaneous drainage, and four with external drainage. In group II, three had percutaneous drainage, 15 operative drainage, and two open packing. In group III, 19 patients had operative drainage and two had open packing. Morbidity occurred in 26% of patients in group I, 40% in group II, and 90% in group III (p less than 0.001). Mortality rates were 9% in group I, 25% in group II, and 48% in group III (p less than 0.01). Enteric organisms were present in 66% of isolates, with no difference between groups, suggesting a common mode of infection. CONCLUSIONS: Despite similar bacteriologic findings, infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have significantly different presentations, clinical courses, and outcomes, confirming that they are distinct entities. This distinction is important when therapeutic outcomes are compared. PMID- 1411958 TI - The expanding utility of endoluminal ultrasonography in the management of rectal cancer. AB - BACKGROUND: This study assessed the ability of endoluminal ultrasonography (ELUS) to determine extent of local invasion and lymph node (LN) metastasis of primary rectal tumors, to assist in ELUS-guided pelvic LN biopsies, and to assess invasion of locally recurrent rectal cancers compared to computed tomography (CT). METHODS: Eighty-one patients with rectal adenocarcinoma (n = 67) or villous adenoma of more than 3 cm (n = 14) underwent ELUS with a 360-degree 7.0-MHz transducer For LN biopsy (n = 10), ELUS was used with an 18-gauge core biopsy needle passed transrectally. ELUS and CT were compared in 14 locally recurrent tumors. RESULTS: Staging for primary tumors (ELUS compared with pathologic examination, TNM system) revealed ELUS accurately predicted wall penetration and LN status with 95% confidence intervals of 0.88 to 0.99 and 0.87 to 0.99. Eight cancers were overstaged, and two were understaged by ELUS. ELUS-guided LN biopsy revealed carcinoma (n = 3) or lymphoid tissue (n = 3) in six of 10 patients. Extent of pelvic organ involvement was predicted in 11 of 14 ELUS and eight of 14 CT examinations in recurrent rectal cancer. CONCLUSIONS: ELUS is accurate in staging rectal cancers, can guide biopsies of pararectal LNs, and may be more reliable than CT in assessing local recurrence. The role of ELUS in the management of rectal cancer is expanding. PMID- 1411959 TI - Indications for enteric conversion after pancreas transplantation with bladder drainage. AB - BACKGROUND: Bladder drainage has become the procedure of choice for 94% of transplant centers in North America. Bladder drainage is superior to other techniques as far as graft survival and technical success are concerned; however, the procedure is associated with significant urologic problems that might necessitate conversion to enteric drainage. This review summarizes the indications and results for enteric conversion at this institution. METHODS: Between June 1982 and January 1992 a total of 240 pancreas transplantations were performed at our center. In 229 cases exocrine secretions were drained into the bladder. These cases were reviewed, and those with enteric conversions were further analyzed to delineate indications, complications, and results. RESULTS: Sixteen (7%) were converted to enteric drainage (side-to-side duodenojejunostomy). The reasons for conversion were urethral disruption (six), recurrent urine leaks (five), bleeding (four), and chronic urinary tract infection (one). Enteric conversions were performed between 1 1/2 and 32 months after the initial transplantation. With the exception of one anastomotic leak resulting in an intraabdominal abscess, no complications occurred. All patients undergoing enteric conversions had resolution of their problems and, in addition, were able to discontinue use of oral bicarbonate. CONCLUSIONS: We conclude that enteric conversion after pancreas transplantation with bladder drainage is safe and effective in the correction of urologic problems. Based on our experience, we recommend early enteric conversion if urologic problems do not resolve after an appropriate period of conservative therapy. PMID- 1411960 TI - Fine structure of presynaptic axonal terminals in sympathetic autonomic ganglia of aging and diabetic human subjects. AB - The neuropathologic changes that may underlie autonomic nervous system dysfunction in nondiabetic elderly human subjects or as a complication of diabetes have been systematically examined in sympathetic ganglia of a series of autopsied human subjects. As in animal models of aging and diabetes, enormously swollen terminal axons were found closely apposed to the perikarya of principal sympathetic neurons in prevertebral superior mesenteric sympathetic ganglia of aged and diabetic human subjects. Dystrophic axons consisted of two stereotyped forms: the first was composed of large numbers of misaligned aggregates of neurofilaments surrounded by variable numbers of small dense core vesicles; the second was characterized by large numbers of mitochondria, vacuoles, and dense and multivesicular bodies. The fine structural characteristics of neuroaxonal dystrophy, its predilection for prevertebral rather than paravertebral sympathetic ganglia, and the tendency for multiple dystrophic axons to cluster preferentially around selected neurons were identical in aged and diabetic human ganglia and were similar to changes seen in animal models of aging and diabetes. Neither diabetic nor aging ganglia demonstrated evidence of neuronal degeneration. Such structural changes may represent a degenerative influence of diabetes and aging on the normal remodeling of nerve terminals in autonomic ganglia, i.e., the continually ongoing process of turnover and replacement of axonal terminals. Similarity of lesions in human diabetes and aging suggests the possibility of pathogenetic mechanisms that are common to diabetes and the aging process. The substantial parallels between humans and animal models provide support for the validity of testing some proposed pathogenetic mechanisms directly in animal models. PMID- 1411961 TI - High-affinity binding of [125I]RTI-55 to dopamine and serotonin transporters in rat brain. AB - RTI-55 (3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester), one of the most potent inhibitors of dopamine uptake reported to date, was radioiodinated and tested as a probe for the cocaine receptor in Sprague-Dawley rat brain. Saturation and kinetic studies in the striatum revealed that [125I]RTI 55 bound to both a high- and low-affinity site. The Kd for the high-affinity site was 0.2 nM, while the Kd for the low-affinity site was 5.8 nM. The corresponding number of binding sites in the striatum was 37 and 415 pmol/g protein. The pharmacological profile of specific [125I]RTI-55 binding in the striatum was consistent with that of the dopamine transporter. Additionally, [125I]RTI-55 was found to bind with high affinity to the cerebral cortex. Scatchard analysis revealed a single high-affinity component of 0.2 nM with a density of 2.5 pmol/g protein. The pharmacological profile demonstrated by [125I]RTI-55 in the cerebral cortex matched that of the serotonin transporter. Autoradiographic analysis of sagittal brain sections with [125I]RTI-55 binding was consistent with these findings. Specific binding of [125I]RTI-55 was blocked by dopamine uptake inhibitors in areas rich in dopaminergic nerve terminals. Conversely, serotonin uptake inhibitors blocked the binding of [125I]RTI-55 in brain areas rich in serotonergic neurons. These results demonstrate that [125I]RTI-55 may be a very useful ligand for the dopamine and serotonin transporters. PMID- 1411962 TI - In vivo binding of [125I]RTI-55 to dopamine transporters: pharmacology and regional distribution with autoradiography. AB - Previous studies have demonstrated that para-substituted WIN 35,065-2 analogs of cocaine show high binding affinity for dopamine uptake sites both in vitro and in vivo, and inhibit DA uptake in vitro. These analogs also produce potent cocaine like behavioral effects in various procedures. The purpose of the present studies was to evaluate the iodinated WIN 35,065-2 analog [125I]RTI-55 as an in vivo ligand for the DA transporter. Following intravenous injection in mice, [125I]RTI 55 showed highest accumulation in areas with high densities of dopamine uptake sites. Light microscopic autoradiography was used to examine binding with higher resolution. Displacement studies demonstrated that [125I]RTI-55 binding in dopamine containing regions, striatum and olfactory tubercles, was saturable and inhibited by other cocaine analogs. GBR 12909 and WIN 35,428 significantly inhibited [125I]RTI-55 binding in striatum, while paroxetine significantly inhibited hypothalamic binding but had little effect in striatum. The latter finding suggests that [125I]RTI-55 also binds to the serotonin transporter. Haloperidol had no effect on [125I]RTI-55 binding in any brain region measured. In addition, treatment of animals with the dopamine neurotoxin MPTP caused significant reductions in striatal [125I]RTI-55 binding. The results of these studies indicate that [125I]RTI-55 binds primarily to the dopamine transporter in the mouse striatum in vivo. PMID- 1411963 TI - Quantitation of carbon-11-labeled raclopride in rat striatum using positron emission tomography. AB - Using conventional autoradiographic and tissue counting techniques, the experimental quantitation of in vivo kinetics of prospective or established radioligands for PET is animal and labour intensive. The present study tested the feasibility of using PET itself to quantitate the specific binding of [11C]raclopride to rat striatum and to study the effects of experimental manipulation of endogenous dopamine on binding parameters. Carbon-11-labeled raclopride was given i.v. to anaesthetised rats, positioned in a PET camera and dynamic emission scans acquired over 60 min. Time-activity curves were generated for selected regions of interest, representing striatum and cerebellum and the striatal data fitted to a compartmental model, using cerebellum as the input function, thus circumventing the need for individual metabolite-corrected plasma curves. In control rats, the binding potential (BP), defined as the ratio of the rate constants for transfer from "free to bound" and "bound to free" compartments, was of the order of 0.6. This was reduced threefold by predosing with nonradioactive raclopride. Increasing extracellular dopamine levels by predosing with d-amphetamine resulted in a significant decrease in BP whereas reducing extracellular dopamine by predosing with gamma-butyrolactone caused a significant increase. Thus, despite the limitation in spatial resolution of PET, specific binding of raclopride could be assessed from regional time-activity curves from individual rats. The system was sufficiently sensitive that changes in BP could be detected following modulation of endogenous dopamine levels, a finding of potential relevance to the interpretation of clinical PET data. PMID- 1411965 TI - [Health policy--improved treatment in fewer hospitals]. PMID- 1411964 TI - [Working environment. 3 out of 10 occupations break laws]. PMID- 1411966 TI - [My firing]. PMID- 1411968 TI - [Psychological working environment--profession: nurse]. PMID- 1411967 TI - [Labor market--women in jobs in Denmark and the EEC]. PMID- 1411969 TI - [Clinical nursing. Best and cheapest]. PMID- 1411970 TI - [Danish Nursing Council--start on project professional development]. PMID- 1411971 TI - [Asthma--to be young and sick]. PMID- 1411972 TI - [Latvia--thick everyday shadows for the future]. PMID- 1411973 TI - [Latvia--nurses are mostly on their own]. PMID- 1411974 TI - [Todays education builds on days of yore]. PMID- 1411975 TI - [Cancer needs special knowledge]. PMID- 1411976 TI - [Opinion: needed, a broad public discussion]. PMID- 1411978 TI - [A long way toward continuing education]. PMID- 1411977 TI - [Anesthesia--children under anesthesia]. PMID- 1411979 TI - [Education--psychiatry on the move]. PMID- 1411980 TI - [Geriatrics--with care and respect]. PMID- 1411981 TI - [Croatia--hospitals are targets]. PMID- 1411982 TI - [Clinical development--experts in incontinence]. PMID- 1411983 TI - [Education--speaking plainly to the students]. PMID- 1411984 TI - [Teaching hospital--a Utopia?]. PMID- 1411985 TI - [Executive Board]. PMID- 1411987 TI - [Personnel policy: clear guidelines but also flexibility]. PMID- 1411986 TI - [Prevention of AIDS from an ethical viewpoint]. PMID- 1411988 TI - [Education--on equal terms after joint course]. PMID- 1411989 TI - [Eastern Europe--a new era with joint responsibility]. PMID- 1411991 TI - [Aphasia--1000-pictures word]. PMID- 1411990 TI - [Urinary incontinence--close by is taboo. Interview by Grethe Kjaergaard]. PMID- 1411992 TI - [England: health under market conditions]. PMID- 1411993 TI - [Education--demand for cost control threatens university. Interview by Grethe Kjaergaard]. PMID- 1411994 TI - [Analysis of a judgment investigation. Incredible]. PMID- 1411995 TI - [I screamed with pain. Interview by Mette-Marie Davidsen]. PMID- 1411996 TI - [History--uniforms as distinctive marks]. PMID- 1411997 TI - [Research--health care in the 90s]. PMID- 1411998 TI - [Work environment--ambitious goals]. PMID- 1411999 TI - [Work environment--a success]. PMID- 1412000 TI - [Analysis of a judgment. Did it happen this way?]. PMID- 1412001 TI - [Prioritizing--quality of life by fractions]. PMID- 1412002 TI - [A breach in hygiene]. PMID- 1412003 TI - [Once upon a time there was...]. PMID- 1412004 TI - [Competition--stories about nursing]. PMID- 1412005 TI - [Nursing stories--finding the right word]. PMID- 1412006 TI - [Nursing stories--a howler]. PMID- 1412008 TI - [Primary nursing care--nursing assistants' last stand]. PMID- 1412007 TI - [Nursing stories--in a foolish mood]. PMID- 1412009 TI - [Primary nursing care--dignity is more important than service]. PMID- 1412010 TI - [District psychiatry. Problems in daily activities]. PMID- 1412011 TI - [District psychiatry. Across professions and sectors]. PMID- 1412012 TI - [Ghosts]. PMID- 1412013 TI - [Heard police beat an inmate. Interview by Mette-Marie Davidsen]. PMID- 1412014 TI - [Unethical to transfer brain-dead patient. Open letter]. PMID- 1412015 TI - [Education: struggle over positions]. PMID- 1412017 TI - [Close the mouth]. PMID- 1412016 TI - [Who wants to have an undergraduate?]. PMID- 1412018 TI - [Care of the dead--a dignified farewell]. PMID- 1412019 TI - [Prioritizing--ethics and quality of life]. PMID- 1412020 TI - [Research: quality of life pitfalls]. PMID- 1412021 TI - [Education: that's why philosophy. Interview by Lars Peter Bergqvist]. PMID- 1412022 TI - [History--regulations and procedures]. PMID- 1412023 TI - [Professional guidance: supervision provides professional pride]. PMID- 1412025 TI - [Nursing--lend a hand to hygiene]. PMID- 1412024 TI - [Professional guidance: 2 sides of team work]. PMID- 1412026 TI - [France: while doctors operate]. PMID- 1412027 TI - [Skin irritation from gloves--a problem in dental practice?]. PMID- 1412028 TI - [Allergy and other skin reactions as a result of rubber gloves]. AB - Protective latex surgical gloves and examination gloves may cause allergic contact dermatitis, mainly due to rubber chemicals used in the manufacturing process. Latex proteins in the gloves may cause contact urticaria and even anaphylactoid reactions. Eighty-eight dentists and other members of the dental team were tested for contact allergy to thiuram- and mercapto-derivatives, and for contact-urticaria to latex proteins. All but 5 persons used gloves at least periodically. Fifty-one of 87 of the persons who answered a questionnaire had or had had symptoms from the skin on the hands, but in only 3 cases could allergy to the gloves be proved. Women had more often symptoms than men, and female dentists with symptoms used gloves more often and for longer periods than female dentists without symptoms. It can be concluded that redness of the skin, itching, vesicles and eczema are common symptoms reported in connection with use of gloves, but proved allergy to the gloves is rare. Most symptoms are supposed to be due to skin irritation from the gloves in addition to irritative exposure from handwashing and other chemical irritants in dental work. The nature of the irritative effect from gloves is only partly known and should be studied further. PMID- 1412029 TI - [Permeability of protective gloves to (di)methacrylates in resinous dental materials]. AB - Dentists may develop contact allergy induced by handling resinous dental materials. Vinyl and latex gloves may provide protection against the monomers of these materials during the time it takes for a monomer to permeate the glove. The passage times and rates of penetration of four commonly used (di)methacrylates, HEMA, TEGDMA, BISGMA and UEDMA for 11 protective gloves were measured. The passage time in vinyl gloves for HEMA and TEGDMA was about 2 min, and around 20 min for BISGMA and UEDMA. The rates of penetration of HEMA and TEGDMA in vinyl gloves were between 1 and 4 mumol.min-1.cm-2. The passage times of HEMA and TEGDMA through most of the latex and modified latex gloves were between 5 and 8 min and the rates of penetration between 0.5 and 1 mumol.min-1.cm-2. Latex and modified latex gloves provide protection against BISGMA and UEDMA in 80 min or more with one exception (Elastyrene), which burst after about 50 min in contact with the resins. Of the tested gloves Ansell, Neutralon, Mediglove and Biogel D provide protection against HEMA and TEGDMA for at least 5 min. PMID- 1412030 TI - [Early appearance of occupational skin irritation in dental practice]. PMID- 1412031 TI - [Necrotizing sialometaplasia]. AB - Necrotizing sialometaplasia is a benign, self-limiting disease that requires no treatment. It is often confused with malignancy, resulting in unnecessary, extensive surgery. Clinicians need to be aware of this lesion and include it in a differential diagnosis of ulcerated lesions, especially in the hard palate. Correct diagnosis depends upon histological diagnosis by a pathologist who is familiar with the characteristics of this disease. One case is presented and the total number in our department from 1985-1991 is summarized. PMID- 1412032 TI - [From fault to rigid connection]. PMID- 1412033 TI - [Dental impressions from Sudan]. PMID- 1412034 TI - [Glass-ionomer cements: composition and technical properties]. PMID- 1412036 TI - [Glass-ionomer cements and fluorides]. PMID- 1412035 TI - [Biological properties]. PMID- 1412037 TI - [Tunnel preparations]. PMID- 1412038 TI - [Glass-ionomer cements as base material and dental bonding]. PMID- 1412039 TI - [Cementation with glass-ionomer cement: types and clinical progress]. PMID- 1412040 TI - [Glass-ionomer cements as building material]. PMID- 1412041 TI - [Glass-ionomer cements and dental sealing]. PMID- 1412042 TI - [Results after short- and long-term observations of bone transplantation to vertical, marginal bone defects]. AB - The effect of autologue bone transplantation to 26 vertical, marginal bone defects has been investigated on a long-term scale ranging from 2 to 26 years. The operation technique included excision of gingival pocket epithelium, removal of granulation tissue, and cleansing of the root surface with scalers. The bone cavities were filled preferably with cancellous bone chips, usually from the patients' upper third molar region. After suturing, the area was covered with a wound paste for 12-14 days. Loosened teeth were splinted for at least 2 months. In 25 of 26 teeth (96%) a bone regeneration was observed radiographically. The maximum healing of 22 cases occurred 2-12 months (median 6 months) postoperatively (Table 1). The maximum healing was maintained for more than half of the teeth (56%) at the last control, median 16 years (range 2-26 years), and none of these teeth were extracted of periodontal causes. They might therefore be expected to function for still a long time. Eight teeth (32%) showed more or less recurrence when controlled 5 to 15 years (median 10 years) after operation and 6 of the 8 teeth with recurrence were extracted. Three teeth (12%) developed root resorption and were extracted 6, 10 and 14 years postoperatively. As most of the complications occurred after extended observation periods, this factor has to be taken into account when prognosis of periodontal treatment procedure is considered. PMID- 1412044 TI - [Dental and other impressions of Taiwan]. PMID- 1412045 TI - [Argument about oral mucous membrane epithelium]. PMID- 1412043 TI - [Effect of irradiation with dental polymerized lamps on human Langerhans cells: a study made on human skin transplanted to nude mice]. AB - Light polymerized composite resin materials are now widely used in dentistry. Most resins are polymerized by light sources which have a powerful emission of visible light and a small emission in the ultraviolet light A spectrum (UV-A 320 400 mm). Possible eye damage, induced by such light, has been investigated, but the effects on the oral mucosa, which is directly exposed to the light, have been examined in only one animal study. Langerhans cells (LC) are dendritic non epithelial cells which form a network within stratified epithelia. LC have features of macrophages, functions as antigen-presenting cells, and play an important role in the immune system associated with skin and oral mucosa. Pilot studies on human skin transplanted to nude mice showed that radiation with small therapeutic doses from a dental light curing unit (DLU) having only a small fraction of UV-light can reduce or deplete the OKT6 surface marker of LC in human epithelium. Further investigation of the photobiologic mechanisms involved spectral analyses of the emmission from the lamps and construction of a suitable light source for establishing an action spectrum for LC in the UV-A range. The action spectrum for LC in the UV-A range was obtained by exposing human skin, grafted to nude mice, to monochromatic light with a band pass of 5-10 nm. Criterion for threshold doses was total depletion of LC, visualized by staining with known LC-markers, monoclonal antibodies OKT6, DAKO-Vimentin, DAKO-HLA-DR and DAKO-S-100. The action spectrum for LC consisted of a biphasic curve, with a non linear, strong wave-length dependency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412046 TI - [Development of dentistry]. PMID- 1412047 TI - [Dentist and physician integrated training at the Health Sciences Faculty at Copenhagen]. PMID- 1412049 TI - [Single-side fracture of mandibular condyle]. PMID- 1412048 TI - [A comparison of two methods for pre-operative radiographic examination in treatment with oral implants in the anterior mandibular area]. AB - Insertion of osseointegrated implants in the anterior mandibular region for retaining a removable denture represents a treatment, which is cheap for the patient and surgically uncomplicated. Bone height measures from two radiographic examinations 1) panoramic radiographs and 2) lateral tangential views, were compared. Radiographs from 20 patients were analyzed. The vertical height of the mandible was measured in the midline as well as in the cuspid region on the panoramic radiographs and the tangential views ("maximum" bone heights). The mean maximum bone heights were higher on tangential views in both regions. On the tangential views the inclinations of the future implants were estimated and the part of the alveolar ridge having a width less than 5 mm, which is the minimum width for housing an implant, was compiled. The resulting height ("effective bone height") was calculated. In 10% of the cases the effective bone height was equal to the maximum height, and in 90% it was smaller. The over-estimation varied between 0 mm and 15.3 mm. It is concluded that panoramic radiographs are unreliable for evaluating bone height in planning insertion of oral implants in the anterior mandibular region. They give no information about form and width of the bone. Tangential views reveal the true morphology of the mandible as seen in a cross-section, and offer an opportunity for calculating the effective bone height at disposal for oral implants. PMID- 1412050 TI - [Lymphangioma of the tongue: case report and review of the literature]. AB - A case of lymphangioma in the tongue is discussed with special reference to diagnosis, treatment and prognosis. The patient is a boy, aged 13, with a congenital malformation in the right half of the tongue. The lesion was removed by surgery. Histologic examination showed lymphangioma. In cases of minor, localized lymphangiomas the clinical diagnosis may be difficult. A past history information of recurring swellings can be regarded as almost diagnostic. The treatment of choice is surgery, if necessary in several settings. Recurrences are often seen. PMID- 1412051 TI - [Hemangioma of the maxilla]. AB - A patient with a cavernous hemangioma of the maxilla is presented. The tumor had caused resorption of the roots af adjacent teeth. After enucleation, the area healed without complications, and the pulpal tissues of the teeth remained vital. PMID- 1412052 TI - Comments on "Reply to 'Comments on "Moebius syndrome: animal model--human correlations and evidence for a brainstem vascular etiology"'". PMID- 1412053 TI - Conjoined twins: theoretical embryologic basis. AB - A theoretical basis for the embryology of conjoined twins was formulated from clinical experience with ten cases and extensive review of pertinent embryologic and clinical literature, including over 500 cases. Regarding the age old question of fusion or fission, it is concluded that there is no known embryologic process by which conjoined twins can be formed by fission but firm evidence to support fusion in all cases. Whether the fusion occurs between embryos on one embryonic disc or on two is of no consequence since they are all monovular. Intact ectoderm will not fuse to intact ectoderm, and all seven types of conjoined twins are explained by seven possible sites of union in the early embryo. One new term is proposed: parapagus, from the Greek para, meaning "side," combined with pagus, meaning "fixed"; this is the group formerly called dicephalus or diprosopos. These anterolaterally united parapagus twins must result from two nearly parallel notochords in close proximity; craniopagi and pygopagi from fusion at the cranial and caudal neuropores, respectively; cephalopagi and ischiopagi from union at the pharyngeal and cloacal membranes, respectively; thoracopagi from merging of the cardiac anlage; and omphalopagi from fusion of the umbilicus or of the edges of two embryonic discs in any area not including the above sites. Parasitic twins result from embryonic death of one twin, leaving various portions of the body vascularized by the surviving autosite. The rarity of cases (2) not easily explained by the above theories, and the nearly 6% of twins with two umbilical cords arising from the placenta would seem to support these conclusions. Should one wish to learn the methods of a conjurer, he might vainly watch the latter's customary repertoire, and, so long as everything went smoothly, might never obtain a clue to the mysterious performance, baffled by the precision of the manipulations and the complexity of the apparatus; if, however, a single error were made in any part or if a single deviation from the customary method should force the manipulator along an unaccustomed path, it would give the investigator an opportunity to obtain a part or the whole of the secret.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1412054 TI - Extraembryonic tissue changes induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,4,7,8-pentachlorodibenzofuran with a note on direction of maternal blood flow in the labyrinth of C57BL/6N mice. AB - Histologic changes in extraembryonic and embryonic tissues induced by 3 or 6 micrograms 2,3,7,8-tetrachlorodibenzo-p-dioxin/kg (TCDD) or 80 micrograms 2,3,4,7,8-pentachlorodibenzofuran/kg/day (4-PeCDF) were studied 24 h after the last of four daily doses administered orally to C57BL/6N mice on days 10-13 of pregnancy. Both test compounds ruptured (1) the embryo-maternal vascular barrier in the labyrinth, which resulted in hemorrhage of embryonic blood into the maternal circulation, (2) the visceral yolk sac membrane with the embryonic blood from the vitelline vessels escaping into the uterine, exocelomic and amniotic cavities, and (3) the maternal vascular spaces of the placental periphery resulting in hemorrhages into the interconceptal space. The role of the hemorrhagic lesions in the induction of cleft palate and hydronephrosis by the two compounds remains to be investigated. The presence of embryonic nucleated erythroblasts that hemorrhaged into the maternal lacunar network allowed the identification of maternal venous channels in the placenta. It revealed that (1) the labyrinth could be tentatively divided into two caudocranially oriented zones, an arterial and a venous zone; (2) the maternal blood in the labyrinthine lacunae circulated from the arterial to the venous zone, somewhat parallel to the uterine axis; and (3) the largest maternal vessels in the center of the placenta hitherto named the "central maternal artery," was in fact, venous. PMID- 1412055 TI - Axial skeletal malformations induced by acetazolamide in rabbits. AB - In order to evaluate the teratogenic potential of acetazolamide in rabbits, three groups of 18 artificially inseminated females were treated orally with 50, 100, or 150 mg/kg/day of acetazolamide on days 6-18 of gestation. These doses induced maternal acidosis and electrolyte changes, consistent with those reported in rats and considered to be a result of carbonic anhydrase inhibition, as well as reductions in maternal body weight gain. At cesarean sections, average fetal body weights in the acetazolamide groups were dose-dependently decreased compared with controls. There were no effects of acetazolamide on embryonic survival or external morphology of live fetuses. In the fetal skeletal examination, thoracic and lumbar vertebral malformations occurred in 0.7%, 3.9%, and 6.1% of fetuses in the 50, 100, and 150 mg/kg/day groups, respectively, compared with none in the control group. In addition, missing vertebra was seen in a small number of fetuses in the 100 and 150 mg/kg/day groups. These axial skeletal malformations were, in some cases, associated with costal malformations. These results indicate that acetazolamide at maternotoxic doses can produce axial skeletal malformations in the rabbit. PMID- 1412056 TI - Analysis of high dysmorphogenic activity of Ro 13-6307, a tetramethylated tetralin analog of retinoic acid. AB - Certain synthetic retinoids differ widely from retinoic acid (RA) in teratogenic potency, being much more or much less effective than RA. It is assumed that the potency of a retinoid may depend on the nature of its interaction with cellular binding components (nuclear retinoic acid receptors or cytoplasmic binding proteins) and, as in the case of retinoids that are mammalian teratogens, on factors that determine its accessibility to the embryo. To investigate some of the factors that contribute to potency, we used a new synthetic retinoid Ro 13 6307 that differs in structure from RA in having an aromatic ring inserted in its side chain along with gem dimethyl modification of the natural cyclohexenyl ring. Pregnant ICR mice were given a single oral dose (0, 1, or 10 mg/kg) on day 11 of gestation, and the resultant teratogenic outcome was monitored on day 17. Direct effects on cell differentiation were obtained by exposing high density cultures of limb bud mesenchymal cells to a range of concentrations (0.3 ng/ml-3 micrograms/ml) of Ro 13-6307 and scoring for chondrogenic suppression. Concentrations reaching the embryo after maternal administration of Ro 13-6307 were measured by HPLC to quantify the analog for a period of 4 h after administration of the oral dose. We found that this retinoid was 40-fold as active as RA in both inducing teratogenesis and suppressing chondrogenesis, yet its concentration in the affected embryo was only a fraction of that achieved after an equivalent dose of RA was employed in a similar protocol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412057 TI - Trends in rates of multiple vascular disruption defects, Atlanta, 1968-1989: is there evidence of a cocaine teratogenic epidemic? AB - Research suggests that, perhaps through mechanisms initiated by vasoconstriction and leading to vessel thrombosis or embolism, cocaine causes vascular disruption defects, and that frequent cocaine use during early pregnancy could disrupt multiple organ systems in the fetus. We hypothesized that if cocaine is an important cause of multiple vascular disruption defects, a rising prevalence of cocaine use by mothers during pregnancy should be accompanied by rising rates of these defects in their offspring. Using data from the Metropolitan Atlanta Congenital Defects Program, we identified all infants born in Atlanta from 1968 through 1989 who had nonsyndromic, provisional vascular disruption defects affecting more than one organ system: 61 infants (78%) had gastrointestinal and genitourinary defects, 7 (9%) had gastrointestinal and abdominal wall defects, 2 (3%) had gastrointestinal and limb reduction defects, 2 (3%) had limb reduction and abdominal wall defects, 2 (3%) had central nervous system and gastrointestinal defects, 2 (3%) had genitourinary and limb reduction defects, 1 (1%) had genitourinary and abdominal wall defects, and 1 (1%) had central nervous system and genitourinary defects. The prevalence of Atlanta infants with more than one vascular disruption defect is 0.13 per 1,000 live births. Chi-square analysis for trends showed no increase in prevalence during the study period. Our data are from one of the first population-based studies in which trends for defects potentially caused by maternal cocaine use are examined; the results of our study show no significant change in the prevalence of multiple vascular disruption defects over time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412058 TI - Growth and differentiation schedule of mouse embryos obtained from delayed matings. AB - We previously showed that digit formation in mouse embryos from early morning mating seemed to progress faster than those from overnight mating. In this study, to confirm this phenomenon, we examine whether the embryos from normal (0 hr from ovulation to fertilization) and delayed matings (3, 6, or 9 hr from ovulation to fertilization) respond differently to some acute teratogens when they are treated at the same time point from mating. Five mg/kg of cytosine arabinoside (Ara-C) was given to pregnant mice intraperitoneally at 246, 249, or 252 hr (day of gestation (dg) 10) after mating. The patterns of Ara-C induced digit malformations in embryos from the delayed mating groups were those of more advanced stages, when compared with normal mating groups with the same time intervals from mating to Ara-C treatment. In other words, oocytes fertilized up to 9 hr after the presumed time of ovulation could grow similarly to those of normally fertilized oocytes. This catch-up phenomenon suggests that the ovulation clock should be used for the startpoint of the time scale of the growth and differentiation of embryos rather than fertilization clock. PMID- 1412059 TI - Variation in development of rat embryos at the presomite period. AB - Rat embryos at a single gestational time in the presomite period were studied for their variation in development and their fate after culture. They were explanted at 8 A.M. on day 9 of gestation from timed-pregnant Sprague-Dawley rats which were obtained by mating between 8 and 10 A.M. (plug day = day 0). In the first experiment, a total of 203 embryos from 20 litters were examined for their variation in development. Several dimensions of embryo/egg cylinder were measured and development of various embryonic/extraembryonic structures were assessed using a scoring system that we developed for the present study. Embryos were then divided into different stages of development based on their scores using the staging system that we developed previously. A large variation in developmental stage was demonstrated; the youngest embryo was at the early primitive streak stage with no signs of amniotic folds and the oldest one was at the late neural plate stage with a foregut pocket but without visible somites. No strong correlation was demonstrated between developmental stage and size of embryo/egg cylinder, nor between developmental stage and development of the proamniotic tube, ectoplacental cavity, or allantois. In the second experiment, embryos were explanted at the same time and those at different stages were cultured separately in rotating bottles and their outcomes were compared after 49 hours. The difference in mean somites number of embryos cultured from the mid primitive streak and late neural plate stages was 6.1. This difference corresponds to approximately 10 hours based on the known linear increase of somites number on day 11 of approximately 0.6 somites per hour. These results indicate a large variation in development of presomite period embryos supposedly of the same gestational age and suggest the importance of careful staging at the time of explantation if precision is needed for whole embryo culture experiments. PMID- 1412060 TI - Increased postimplantation loss and malformations among the F2 progeny of male rats chronically treated with cyclophosphamide. AB - Cyclophosphamide, administered to the male rat, produces increased pre- and postimplantation loss in the progeny as well as an increase in the numbers of malformed and growth retarded fetuses. The purpose of this study was to determine whether the adverse effects of chronic paternal cyclophosphamide exposure are transmissible to the next generation, the F2 progeny. Adult male rats were treated by gavage daily with saline or with cyclophosphamide (3.4 or 5.1 mg/kg) for 4 or 18 weeks and mated. The male and female offspring in each treatment group (F1 generation) were randomly mated. The resulting pregnant females were killed on day 20 of gestation to evaluate progeny outcome in the F2 generation. There was a significant increase in postimplantation loss among the offspring of the group whose fathers had been treated with cyclophosphamide at a dose of 5.1 mg/kg/day. Exposure to a dose of 5.1 mg/kg/day of cyclophosphamide also resulted in an F2 generation with a significantly decreased mean fetal weight per litter and a significant increase in the number of malformed fetuses. The malformations observed among the F2 progeny included open eyes, omphalocele, generalized edema, syndactyly, gigantism, and dwarfism. Thus, exposure of the father to cyclophosphamide does result in a specific and heritable alteration in the fertility of the surviving "apparently normal" F1 progeny. Interestingly, the adverse consequences of exposure of male rats to cyclophosphamide are similar in the F2 generation to those previously reported for the F1 progeny. PMID- 1412061 TI - Further genetic studies of the cause of exencephaly in SELH mice. AB - We have developed an inbred stock of mice called SELH that has a high frequency of the neural tube defect exencephaly at birth. A previous genetic study indicated that the exencephaly is due to two to three additive loci differing between SELH and a closely related normal strain, ICR/Bc, but this analysis was not designed to detect genetic maternal effects. Recently, we demonstrated that there is genetic polymorphism among normal mouse strains leading to differences in site of initiation of closure of the cranial neural tube. In the present study, an inbred substrain of SELH mice, with 24% exencephaly among embryos, was crossed with an unrelated normal strain, SWV/Bc, and the frequency of exencephaly in subsequent generations used to extend our understanding of the genetic cause of exencephaly in SELH mice. The purposes of the genetic studies reported here were twofold. First, based on the influence of genetic maternal effects on other genetically complex birth defects in mice, we hypothesized that the exencephaly of SELH mice would exhibit strong genetic maternal effects. This hypothesis was tested by comparisons among the four possible reciprocal backcrosses to SELH. The result was an overall frequency of 2.3% exencephaly in first backcross embryos with no difference among the four crosses and no evidence of genetic maternal effects. Second, the frequency of exencephaly recovered in the backcross and F1 embryos was compared with the previous genetic study and with various genetic models. The frequencies were similar to those obtained from the cross to ICR/Bc mice and were compatible with a hypothesis of additive gene action at a few loci.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412062 TI - Effect of ACE inhibition on the fetal kidney: decreased renal blood flow. AB - The kidneys of nine fetuses whose mothers were chronically hypertensive were examined microscopically. Three of these mothers used antihypertensive agents throughout pregnancy including one who used an angiotensin-converting enzyme (ACE) inhibitor. The tubular defects found in these kidneys were compared to the kidneys of 20 normal controls, 13 fetuses with various multiple malformation syndromes and six cases of the twin to twin transfusion syndrome. Evidence from these cases as well as the literature suggest that the primary mechanism by which ACE inhibitors affect development of the fetal kidney is through decreased renal blood flow. PMID- 1412063 TI - Pathogenesis of ethanol-induced limb reduction defects in mice. AB - Acute administration of dosages of 2.5, 2.8, or 2.9 g/kg of ethanol to pregnant C57BL/6J mice on gestational day 9 1/4 resulted in major malformations of the forelimb including postaxial ectrodactyly, preaxial syndactyly, and reduction defects involving intermediate digits. The incidence and severity of these defects was positively correlated with dosage. Sidedness of the defects was also dose-dependent. In affected embryos, excessive amounts of cell death were notable within 5-9 hr of treatment initiation in selected cell populations. Cell death was primarily distributed in two regions of the developing limb bud--a ventrodistal ectodermal cell population (apical ectodermal ridge) and a proximal mesenchymal cell population. The patterns of cell death observed appear to be pathogenically related to the limb defects noted at later stages. In particular, it would appear that the deficiencies in the apical ectodermal ridge resulting from ethanol-induced cell death can account for virtually all the subsequent limb defects. PMID- 1412064 TI - A decade of rabbit fertility data: study of historical control animals. AB - Reproductive data for 1795 artificially inseminated Hra: (NZW)SPF control rabbits in 93 developmental toxicity studies conducted from 1980 through 1989 were summarized. Data were obtained during terminal Caesarean-sectioning procedures performed on animals which survived to day 29 of gestation and during postmortem evaluation of does which aborted, delivered prematurely, or were found dead. Significant seasonal variation was not observed. Average pregnancy rate, percentage of rabbits that aborted, and percentage of rabbits that delivered prematurely throughout the decade were 86, 2.0, and 1.6%, respectively. Average numbers of corpora lutea, implantations, live fetuses, dead fetuses, early resorptions, and late resorptions for each doe that survived to scheduled termination were 10.8, 7.8, 7.1, 0.02, 0.49, and 0.15, respectively. The various vehicles used, routes of administration, and a variety of maternal and paternal factors were compared with the fertility data, and no correlations were observed. Rabbits that aborted earlier in gestation had fewer implantations than does which aborted late or delivered prematurely. Does which resorbed 100% of their conceptuses had fewer corpora lutea and implantations when compared with rabbits in the remainder of the population. Rabbits pregnant at scheduled termination which had a low number of corpora lutea or implantation sites had higher than expected pre- and postimplantation losses relative to the population as a whole. Does with a high number of corpora lutea had significantly higher preimplantation loss relative to the general population. This may indicate the presence of a "ceiling value" for the number of ova that can become fertilized and/or implant when the ovulation rate is high and which probably varies according to strain as well as a number of factors related to the individual rabbit. Based upon the results of this study and the work of a previous author, a minimum of four corpora lutea may be necessary for the successful maintenance of pregnancy in the New Zealand white rabbit. The minimum number of corpora lutea required may be strain dependent and may bear a relationship to the normal litter size of the strain. PMID- 1412065 TI - Serotonin as a regulator of craniofacial morphogenesis: site specific malformations following exposure to serotonin uptake inhibitors. AB - During craniofacial development in the mouse embryo (days 9-12 of gestation; plug day = day 1), transient expression of serotonin (5-HT) uptake in epithelial structures of this region correlates with critical morphogenetic events (Lauder et al., '88; Shuey, '91; Shuey et al., '89, '92). The purpose of the present investigation was to assess the possible functional significance of these uptake sites by examination of patterns of dysmorphology following exposure of embryos to selective 5-HT uptake inhibitors. Exposure of mouse embryos in whole embryo culture to sertraline, at a concentration (10 microM) which produced no evidence of general embryotoxicity, caused craniofacial malformations consistent with direct action at 5-HT uptake sites. Two other 5-HT uptake inhibitors, fluoxetine and amitriptyline, produced similar defects. The critical period of sertraline exposure occurred on days 10-11. The observed craniofacial defects were associated with decreased proliferation and extensive cell death in mesenchyme located 5-6 cell layers deep from the overlying epithelium. In contrast, the subepithelial mesenchymal layers showed normal or elevated levels of proliferation. From these results it appears that inhibition of 5-HT uptake into craniofacial epithelia may produce developmental defects by interference with serotonergic regulation of epithelial-mesenchymal interactions important for normal craniofacial morphogenesis. PMID- 1412066 TI - The warfarin embryopathy: a rat model showing maxillonasal hypoplasia and other skeletal disturbances. AB - Sprague-Dawley rats were given daily subcutaneous doses of sodium warfarin (100 mg/kg) and vitamin K1 (10 mg/kg) for up to 12 weeks, starting on the day after birth. This dosing regimen creates an extrahepatic vitamin K deficiency while preserving the vitamin K-dependent processes of the liver. Control rats received either vitamin K1 only or were untreated. All rats survived without any signs of hemorrhage. The warfarin-treated rats developed a marked maxillonasal hypoplasia associated with a 11-13% reduction in the length of the nasal bones compared with controls. The length of the posterior part of the skull was not significantly different from controls. In the warfarin-treated rats, the septal cartilage of the nasal septum showed large areas of calcification, not present in controls, and abnormal calcium bridges in the epiphyseal cartilages of the vertebrae and long bones. The ectopic calcification in the septal cartilage may have been the cause of the reduced longitudinal growth of the nasal septum and the associated maxillonasal hypoplasia. It is proposed that (1) the facial features of the human warfarin embryopathy are caused by reduced growth of the embryonic nasal septum, and (2) the septal growth retardation occurs because the warfarin-induced extrahepatic vitamin K deficiency prevents the normal formation of the vitamin K dependent matrix gla protein in the embryo. PMID- 1412068 TI - Nursing is a science and an art: a hero story. PMID- 1412067 TI - The effects of continuous exposure to 20-kHz sawtooth magnetic fields on the litters of CD-1 mice. AB - Mated CD-1 mice were exposed to 20-kHz sawtooth magnetic fields similar to those associated with video display terminals (VDT). Four groups of animals were continuously exposed from day 1 to day 18 of pregnancy to field strengths of 0, 3.6, 17, or 200 microT. There were no less than 185 mated dams in each exposure group. On day 18, the dams were sacrificed and assessed for weight gain and pregnancy. The litters were evaluated for numbers of implantations, fetal deaths and resorptions, gross external, visceral and skeletal malformations, and fetal weights. There were no less than 140 pregnant females in each group, and there were no significant differences between any of the exposure groups and the sham group (0 microT) for any of the end points. The results of this study do not support the hypothesis that the 20-kHz VLF magnetic fields associated with video display terminals are teratogenic in mammals. PMID- 1412069 TI - AIDS Q&A. PMID- 1412070 TI - Stop the beating: a report on domestic violence. PMID- 1412071 TI - Niche breadth in parasites: an evolutionarily stable strategy model, with special reference to the protozoan parasite Leishmania. AB - A parasite's host range essentially defines its niche breadth, which, as foraging theory predicts, is influenced by resource availability. For parasites, the interaction of infection and transmission characteristics with host population dynamics determines host availability. An epidemiological model, involving two host types and describing competition between a "generalist" parasite strain and a related "specialist" strain, is used to examine the interplay among host range, relative host availabilities, and adaptational compromises engendered by increased host range. Results show that the generalist can predominate even when it cannot maintain itself in either host alone, but that the specialist can persist if its reproductive rate attains some threshold relative to either of the generalist's respective rates in its two hosts. The model is in rough, qualitative agreement with observed dynamics of two Leishmania parasite-host systems, and overall results suggest that infection of two species with a common parasite can lead to complex, indirect coevolutionary dynamics. PMID- 1412072 TI - Of Nobel class: a citation perspective on high impact research authors. AB - The purpose of this paper was to determine if quantitative rankings of highly cited research authors confirm Nobel prize awards. Six studies covering different time periods and author sample sizes were reviewed. The number of Nobel laureates at the time each study was published was tabulated, as was the number of high impact authors who later became laureates. The Nobelists and laureates-to-be were also compared with non-Nobelists to see if they differed in terms of impact and productivity. The results indicate that high rankings by citation frequency identify researchers of Nobel class--that is, a small set of authors that includes a high proportion of actual Nobelists and laureates-to-be. Also, the average impact (citations per author) of Nobelists and laureates-to-be is sufficiently high to distinguish them from non-Nobelists in these rankings. In conclusion, a simple, quantitative, and objective algorithm based on citation data can effectively corroborate--and even forecast--a complex, qualitative, and subjective selection process based on human judgement. PMID- 1412073 TI - Arrhenius vs. Ehrlich on immunochemistry: decisions about scientific progress in the context of the Nobel Prize. AB - This study forms part of a larger research project examining the election process for the Nobel prizes for Physiology or Medicine at the Karolinska Institute in Stockholm, and the role and function of the prizes in early 20th century Swedish and international medicine. The purpose of the study is to clarify the decision making process which led to the Nobel prize for Paul Ehrlich in 1908, 'for work on immunity'. His award was preceded by the most dramatic conflict within the prize authority concerning any prizewinner prior to World War I, and thus is apt to illuminate both the implicit and explicit criteria and the strategies used in the prize deliberations. Ehrlich's chemical ideas on the immune response were criticized by the physical chemist Svante Arrhenius who recommended the application of his disciplines's methods and principles on immunological problems. This criticisms were brought into the Nobel prize debate by J.E. Johansson, a physiologist who asserted that Ehrlich's research was of little scientific value and therefore not worthy of a prize. Yet the majority of the Institute, led by its chairman, the chemist K.A.H. Morner, succeeded in awarding Ehrlich. An analysis of the controversy shows it to be primarily based upon (1) a difference of scientific styles between the antagonists, resulting in incongruous definitions of immunology as a research field, and of the proper aims and methods of immunological studies. Other factors influencing the final decision were (2) the Institute's negative reaction to what was considered an intrusion in medical Nobel prize matters by a chemist, (3) Arrhenius' and Johansson's diverging views on what kind of work should be awarded a prize, and (4) Johansson's position as a non-conformist at the Karolinska. PMID- 1412074 TI - Theory change in immunology. Part I: Extended theories and scientific progress. AB - This two-part article examines the competition between the clonal selection theory and the instructive theory of the immune response from 1957-1967. In Part I the concept of a temporally 'extended theory' is introduced, which requires attention to the hitherto largely ignored issue of theory individuation. Factors which influence the acceptability of such an extended theory at different temporal points are also embedded in a Bayesian framework, which is shown to provide a rational account of belief change in science. In Part II these factors, as elaborated in the Bayesian framework, are applied to the case of the success of the clonal selection theory and the failure of the instructive theory. PMID- 1412075 TI - Theory change in immunology. Part II: The clonal selection theory. AB - This two-part article examines the competition between the clonal selection theory and the instructive theory of the immune response from 1957-1967. In Part I the concept of a temporally 'extended theory' is introduced, which requires attention to the hitherto largely ignored issue of theory individuation. Factors which influence the acceptability of such an extended theory at different temporal points are also embedded in a Bayesian framework, which is shown to provide a rational account of belief change in science. In Part II these factors, as elaborated in the Bayesian framework, are applied to the case of the success of the clonal selection theory and the failure of the instructive theory. PMID- 1412076 TI - The proliferation of prizes: Nobel complements and Nobel surrogates in the reward system of science. AB - In the last two decades, prizes in the sciences have proliferated and, in particular, rich prizes with large honoraria. These developments raise several questions: Why have rich prizes proliferated? Have they greatly changed the reward system of science? What effects will such prizes have on scientists and on science? The proliferation of such prizes derives from marked limitations on the numbers and types of scientists eligible for Nobel prizes and consequent increases in the number of uncrowned laureate-equivalents. These would-be surrogates for Nobel prizes extend the reward system of science in its upper reaches but this change is not fundamental. The spread of rich prizes to new fields provides added incentives to potential winners, which has its own disutilities; it reinforces competitiveness, concern for priority and attendant secrecy, all this amplifying ambivalence toward the reward system in science. There may also be modest positive effects of such new awards in the form of heightened popular esteem for science and interest in it. PMID- 1412077 TI - Discovery, theory change, and the Nobel Prize: on the mechanisms of scientific evolution. An introduction. PMID- 1412078 TI - [Basic considerations in the rehabilitation of foreign workers]. AB - Rehabilitation involves executive duties, the patient must actively cooperate with the rehabilitation team, and both sides must set clear goals. In the case of rehabilitation of foreigners, it is difficult to set goals because of language and cultural differences. The rehabilitation clinic in Bellikon hospitalizes so many foreigners that it decided to comply with their demands by choosing a specific personnel. In fact, with the purpose of improving the basis for communication, the clinic employs therapists and nursing staff that come from other countries and cultures, offering them further vocational training, too. Not only should misunderstandings and feelings of frustration be avoided as far as possible, but interactive therapy should become the foundation stone for a successful treatment and rehabilitation. The conference on rehabilitation that was organized by the SAR in autumn 1991 made up a part of these efforts. PMID- 1412079 TI - [Immigrants in Switzerland: possibilities and difficulties of integration]. AB - Immigrants find it hard--although not all in the same way--to adapt to the language, the social structure and the way of life of their host country. Different factors overlap: the foreigners' social and cultural background, their education and their adaptability to a foreign environment, their plans for the future, the political and legal situation in the host country as well as the local population's acceptance of and tolerance and respect for a foreign culture. The fact that 75% of all foreigners in Switzerland possess a residence permit can be considered as rather positive; however, this does not necessarily mean that these people are familiar with the local language and way of life. Isolation and a continuously postponed return to the home country are conditions well known even among resident foreigners. Seasonal workers, on the other hand, feel great uncertainty and concern. In critical life situations, for instance caused by illness, accidents or unemployment, the process of rehabilitation can strongly be influenced by earlier living conditions. The Swiss legislation on foreigners as well as the legislation on social security can often bring about fundamental fateful questions. In order to find efficient solutions to the wide range of possible difficulties, a whole-hearted interdisciplinary cooperation is extremely important. PMID- 1412080 TI - [Sinistrosis: cultural approach to understanding chronicity and its economic aspects]. AB - Migration-related health problems can be acute and/or chronic. The chronization is a characteristic of sinistrosis, a multi-institutional phenomenon in which the patient-clinician relationship is trapped in a dead end. To unlock this situation, the author proposes an explorative methodology for case-history making that focuses on the economic aspect of sinistrosis. PMID- 1412081 TI - [Prevalence and persistence of back pain in foreign workers: class or culture induced?]. AB - Physically working people are more likely to suffer from backache. Not only is their work hard and menial but usually also degrading. Unpleasant circumstances such as an offensive environment, the monotony of work, poor qualifications or unsatisfactory work generally influence the persistence of pain. The course of an illness such as a lingering backache, is hardly ever determined by somatic factors. A prognosis is rather based upon the attitude and behaviour of the single patient and his social surroundings, as well as upon the pathological process. Medication might even worsen rather than improve the patient's condition. The typical foreign worker, who generally merely has an elementary education and whom we therefore assign unqualified work, does not only risk to suffer from backache. His personal strength and his circumstances can seriously hinder his rehabilitation, more than it would be the case with native patients. The accumulation of negative factors is closely connected to his role of a foreign worker, whereas cultural aspects do not seem to be determining. Therefore, the foreign patient's rehabilitation can be fostered and improved by adopting the same methods used with Swiss patients against the chronicisation of backache. Nevertheless, the mentioned unfavourable factors and additional language problems considerably foil all efforts to a successful rehabilitation. PMID- 1412082 TI - [Experiences in family therapy with immigrants]. AB - By emigrating, the foreigner has to meet with various expectations and therefore stands under pressure. On one hand, his decision is closely linked to his wish for new achievements and prosperity--his relatives and friends attentively watch over him to make sure that he succeeds. On the other hand, the new environment requires him to adapt to new ways of thinking and behaving. His own values are neither followed anymore nor considered as general guideline through everyday life. In a relatively short time, therefore, the emigrant has to make the strenuous effort to change his views, even if it involves neglecting old family traditions. For the emigrant these demands are often too excessive, so that he becomes insecure and sceptical, finally desperately but subconsciously clinging to his traditional values. Furthermore, he might feel to be surrounded by enemies. All that makes the integration become sluggish if not impossible. Mechanisms of thought and behaviour such as these, are the starting point in family therapy with emigrants. The goal is to make the foreigner more aware of his life in emigration. The experience acquired in family therapy is certainly useful in the rehabilitation of foreign workers who have fallen victim to an accident or an illness. PMID- 1412083 TI - [Rehabilitation of foreign workers: myths and reality]. AB - In terms of chances for a successful professional reintegration of a worker who has fallen victim of an accident or an illness, there are no significant differences between Swiss workers and foreign workers. This viewpoint is based on a survey of limited representation. Two groups of 65 and 50 patients from the French speaking part of Switzerland were questioned. The results clearly warn against generalizations, prejudices and cliches. It is wrong to rashly judge a whole cultural or ethnic group only upon one negative experience made with a single person of that group. On the other hand, it is rather significant that the chances for a successful reintegration become smaller for Swiss and foreign workers, the longer it takes to introduce the necessary measures after the beginning of an illness or a handicap. The causes of chronification and interdependence between complex circumstances and conflict situations must be taken appropriately into account with interdisciplinary cooperation. If cases with serious problems can be singled out early, the risk of total disability of the patient can be avoided. PMID- 1412084 TI - [Social counseling for immigrants--practical experiences exemplified by Portugese immigrants]. AB - The basis for an adequate communication being insufficient, it is very hard to offer foreigners in difficult situations efficient advisory assistance and care. The reason is not only the difference in language but also the difference in culture. Not everything can be expressed properly with a literal translation. The statements must be interpreted in connection with the way of thinking and behaving as well as with the cultural, social and religious environment of those seeking advice. According to the Portuguese community as well as all other emigrants, intermediaries of their mother tongue and culture should stand in more frequently. This way, there would be a better chance of success for all people involved. PMID- 1412085 TI - [Rehabilitation of foreign workers from the viewpoint of the foreign police authorities]. AB - When speaking of rehabilitation of a foreign worker who has fallen victim to an accident or an illness, it is important to ask one fundamental question: Should he be reintegrated in the society of his host country or in his home country? The Swiss foreign police authorities play a decisive role in answering this question. Whether a residence permit should be granted, extended or denied depends on their considerations. For this purpose, all decisions taken by the cantonal authorities are based on particularly significant discretionary powers guaranteed by the Swiss legislation on foreigners. Numerous factors are determining for the evaluation of a case. Often, it is difficult to find the appropriate overview for circumstances, so that a sound and farsighted approach is essential, which-for its part-requires a constructive cooperation of all parties involved. PMID- 1412086 TI - [Practical experiences in legal counseling of foreign workers]. AB - When foreign workers ask for legal advice, very often their questions concern primarily insurance rights for disability. Most uncertainties exist about specific clauses in the legislation on disability insurance and about the measurings of disability. Primarily, discussions arise from controversy about claims made to the state disability insurance. The legislation on disability insurance establishes strict requirements for foreigners asking for insurance rights for disability. However, the Agreement on Social Security signed worldwide by over 20 nations being more tolerant in terms of disability insurance, Swiss legislation can be applied only to a minority of foreigners. That is why the system of legislation has become so complex. There are two major points that are rigidly to be observed: On one hand, the process of reintegration measures can start only if the prescribed minimum duration of contributions is guaranteed. On the other, proceedings for disability pensions can be initiated only after the currently valid waiting period. In both cases, it is considerably important that the patient has a domicile in Switzerland or a valid residence permit. Numerous disagreements can possibly result during the evaluation of the degree of disability, as certain factors-such as language problems, lack of education or the labour market situation-, which are not directly linked to the disability, are not taken into consideration. PMID- 1412087 TI - Children and smoking: the problem and the way forward. PMID- 1412088 TI - Endoscopy assisted microthoracotomy. PMID- 1412089 TI - Endoscopy assisted microthoracotomy: initial experience. AB - BACKGROUND: Although thoracoscopy has been used for diagnostic and minor therapeutic procedures for many years, there have been few reports of its use in performing major intrathoracic procedures, which have traditionally required formal thoracotomy. METHODS: Twenty one patients (M:F 1.2:1; mean (SD) age 47.1 (18.8), range 17-75 years) underwent endoscopic intrathoracic surgery. Eight had unidentified peripheral masses on the chest radiograph, eight required lung biopsy, and five had recurrent or persisting pneumothoraces. Under general anaesthesia a laparoscope attached to a video monitor was introduced into the chest. One or two additional stab incisions were made as needed for the introduction of standard surgical or endoscopic instruments and staplers. RESULTS: There were no complications or deaths, though one patient developed a second pneumothorax seven days after endoscopic pleurectomy, necessitating open pleurodesis. All patients were discharged home from two to six days after surgery (mean (SD) 3.7 (1.2) days). CONCLUSION: Endoscopic thoracic surgery is a safe and useful technique for certain cases. It merits further investigation and assessment. PMID- 1412090 TI - Clinicopathological correlations in cor pulmonale. AB - BACKGROUND: The relation between pulmonary disease and physiological abnormality in patients with hypoxic cor pulmonale is controversial and the association between arterial hypoxaemia and right ventricular hypertrophy has been challenged. To address these problems matched patients treated with and without domiciliary oxygen were studied. METHODS: Necropsy data were obtained on 19 patients (14 male), 10 of whom had been treated with domiciliary oxygen. Pulmonary artery pressure and total pulmonary vascular resistance as well as blood gas tensions during the breathing of air and oxygen were available for the six months before death. Formalin fixed lung slices were assessed for panacinar and centriacinar emphysema. Right and left ventricular weights were measured and their ratio (LV&S/RV) was used as an index of right ventricular hypertrophy. Carotid body weights were available in 14 cases. RESULTS: Fourteen patients died of respiratory failure and antemortem thrombus was found in the pulmonary arteries of eight cases. Physiological measurements were unrelated to the degree of macroscopic emphysema, pulmonary hypertension, or daytime blood gas tensions. When allowance was made for the higher "ambient" arterial oxygen tension (PaO2) of those who had oxygen, PaO2 was correlated with LV&S/RV (r = 0.79), absolute right ventricular weight (r = -0.53), and carotid body weight (r = 0.68). CONCLUSIONS: These data show that in hypoxic cor pulmonale in vivo physiological disturbances are poor indicators of the underlying disease process. The relation of "ambient" PaO2 to right ventricular hypertrophy and carotid body weight suggests that domiciliary oxygen therapy might lead to regression of such established disease. PMID- 1412091 TI - The site of disruption of the bronchial epithelium in asthmatic and non-asthmatic subjects. AB - BACKGROUND: Attention has recently been focused on the basal cells of the tracheobronchial epithelium as the mechanism of anchorage of the tall columnar cells, which themselves do not appear to form hemidesmosomes with the basement membrane of the epithelium. Residual basal cells have been described as remaining attached to the basement membrane after epithelial denudation. This led this group to formulate the hypothesis that there may be a potential plane of cleavage between the basal cells and the overlying columnar cell layer within the bronchial epithelium, which becomes disrupted in asthma. METHODS: Bronchoalveolar lavage samples were obtained during bronchoscopy from eight patients with atopic asthma and four normal controls. Ultrathin sections of lavage cell pellets were examined by electron microscopy and the number of columnar and basal cells found in each epithelial cell cluster was counted. Cytocentrifuge preparations of the lavage samples from the same subjects were also examined for free epithelial cells and epithelial cell clusters. RESULTS: Electron microscopic examination of the cell pellets showed that basal cells were present in very small numbers in the epithelial clusters in all subjects (mean 0.03 (SE 0.02)/cluster) and the ratio of columnar cells to basal cells was far greater than was encountered in the intact bronchial epithelium (167 nu 4). The cytocentrifuge preparations showed an increased number of epithelial cell clusters and epithelial cells in the asthmatic patients. Although these clusters were similar in size in the two groups of subjects (6.3 nu 5.1 cells/cluster) the ratio of free epithelial cells to cells within the cluster was higher in the non-asthmatic subjects. CONCLUSIONS: It is proposed that shedding of epithelial cells occurs along a suprabasal plane and that there is a potential plane of cleavage between the suprabasal and the basal cell layers, which might be more vulnerable to the various insults. PMID- 1412092 TI - Quantitative morphology and water distribution of bronchial biopsy samples. AB - BACKGROUND: An approach to the study of the pharmacokinetics of drugs in the lung is to measure their concentrations in bronchial biopsy specimens. The main criticism of this technique is that bronchial biopsy specimens consist of more than one tissue type and that drugs are often not distributed evenly. The morphology of bronchial biopsy specimens and the distribution of water between the extracellular and the intracellular compartments is therefore important. METHODS: Fifteen subjects undergoing fibreoptic bronchoscopy each had four bronchial biopsy samples taken. Thirty sections from 10 patients were examined and the proportion of tissue types noted, a morphometric analysis computer being used. The water distribution was investigated in the other biopsy specimens with radiolabelled markers. RESULTS: There was pronounced variation in the relative proportions of tissue types. Ciliated epithelium occupied a mean of 22.3% of the biopsy sample, submucosa 53.4%, muscle 17.6%, and glandular tissue 7.0%. There were no differences between second and the fourth generation subcarinae and macroscopic normality of the mucosa was a good predictor of histological normality. The extracellular water content was 40% of the total weight of the specimen and the total water content was 70%. CONCLUSIONS: These data provide the basis for pharmacokinetic study of drugs in bronchial mucosa. They show for pharmacokinetic study that macroscopically normal mucosa may be assumed to be histologically normal; that multiple biopsy specimens should be taken for any study, as there is considerable variation in the proportion of tissue types; that specimens from second and fourth generation subcarinae are the same; and that extracellular water contributes 40% to the total weight of the biopsy specimen. PMID- 1412093 TI - Lymphocyte and lymphocyte subset numbers in blood and in bronchoalveolar lavage and pleural fluid in various forms of human pulmonary tuberculosis at presentation and during recovery. AB - BACKGROUND: Lymphocytes have a central role in human defences against mycobacteria. A study was designed to assess the relation between lymphocyte responses and clinical pattern of disease, nutrition and recovery during treatment in patients with tuberculosis. METHODS: Lymphocyte numbers and subsets (on the basis of CD3, CD4, and CD8 monoclonal antibodies) were measured in peripheral blood and, where appropriate, bronchoalveolar lavage or pleural fluid of patients with different forms of pulmonary tuberculosis. Eleven had localised pulmonary tuberculosis, 18 miliary tuberculosis and seven a tuberculous pleural effusion. RESULTS: CD4 lymphocytes were found in greatly increased numbers in pleural fluid and were relatively depleted in the blood. Lymphocyte numbers in bronchoalveolar lavage fluid varied widely in localised pulmonary and miliary tuberculosis but were highest in lavage fluid from patients with miliary tuberculosis. This was due to an increase in CD8 lymphocytes, which were also increased in the blood. Lymphocyte numbers bore no relation to nutrition, symptom duration, or radiographic profusion scores. In miliary tuberculosis the time taken for the chest radiograph to clear (mean (SD) 17.6 (7.8) weeks) correlated with lymphocyte numbers in lavage fluid, especially CD8 cells (r = 0.74), but not with the patients' age or nutrition. After 8 weeks' treatment, total and CD4 lymphocyte numbers in lavage fluid showed a substantial increase. CONCLUSION: The association of CD8 cells with delayed recovery is compatible with suppression of the antimycobacterial action of macrophages. The switch to predominance of CD4 cells in lavage fluid during successful treatment supports the view that they may have a role in eliminating mycobacteria. PMID- 1412094 TI - Predictive equations for total lung capacity and residual volume calculated from radiographs in a random sample of the Michigan population. AB - BACKGROUND: Published predicted values for total lung capacity and residual volume are often based on a small number of subjects and derive from different populations from predicted spirometric values. Equations from the only two large studies gave smaller predicted values for total lung capacity than the smaller studies. A large number of subjects have been studied from a population which has already provided predicted values for spirometry and transfer factor for carbon monoxide. METHODS: Total lung capacity was measured from standard posteroanterior and lateral chest radiographs and forced vital capacity by spirometry in a population sample of 771 subjects. Prediction equations were developed for total lung capacity (TLC), residual volume (RV) and RV/TLC in two groups--normal and total. Subjects with signs or symptoms of cardiopulmonary disease were combined with the normal subjects and equations for all subjects were also modelled. RESULTS: Prediction equations for TLC and RV in non-smoking normal men and women were square root transformations which included height and weight but not age. They included a coefficient for duration of smoking in current smokers. The predictive equation for RV/TLC included weight, age, age and duration of smoking for current smokers and ex-smokers of both sexes. For the total population the equations took the same form but the height coefficients and constants were slightly different. CONCLUSION: These population based prediction equations for TLC, RV and RV/TLC provide reference standards in a population that has provided reference standards for spirometry and single breath transfer factor for carbon monoxide. PMID- 1412095 TI - Effects of posture on flow-volume curves during normocapnia and hypercapnia in patients with obstructive sleep apnoea. AB - BACKGROUND: A high ratio of forced expiratory to forced inspiratory maximal flow at 50% of vital capacity (FEF50/FIF50) may identify upper airway dysfunction. Since hypercapnia increases the motor activity of airway dilating muscles its effects on the maximum expiratory and inspiratory flow-volume curves (MEIFV) in patients with obstructive sleep apnoea and in normal subjects in different postures was studied. METHODS: The effects of posture on the maximum expiratory and inspiratory flow-volume curves during the breathing of air and 7% carbon dioxide in 11 patients with obstructive sleep apnoea were compared with those in nine normal subjects. Measurements were made in the sitting, supine, and right lateral recumbent positions. Forced expiratory flow at 50% vital capacity (FEF50), forced inspiratory flow at 50% vital capacity (FIF50) and FEF50/FIF50 were determined. RESULTS: In the normal subjects FEF50, FIF50, and FEF50/FIF50 were not affected by change in posture or by breathing carbon dioxide. In the patients there was a fall in FIF50 and an increase in FEF50/FIF50 when breathing air in the supine position compared with values in the seated and lateral position. While they were breathing carbon dioxide there was a slight increase in FEF50 when patients were seated or in the lateral position compared with values during air breathing. Hypercapnia abolished the effects of posture on FEF50/FIF50. Values for FEF50/FIF50 in the supine position while they were breathing air correlated with the apnoeic index but not with other polysomnographic data. CONCLUSION: In patients with obstructive sleep apnoea the upper airway is prone to collapse during inspiration when the patient is supine, even when awake; this tendency can be reversed by breathing carbon dioxide. PMID- 1412096 TI - Comparison of the prevalence of asthma among Asian and European children in Southampton. AB - BACKGROUND: Primary health care workers have reported an impression that asthma is commoner among Asian than European children, and a cross sectional survey was designed to compare the prevalence in Asian and European children. METHODS: The survey was carried out in children aged 7-11 in eight primary schools in Southampton. Four schools contained predominantly children of European ancestry, two contained predominantly Asian children, and two contained a mixture of ethnic groups. Data were collected by means of parent completed questionnaire on recent asthma symptoms, diagnosis, morbidity, and treatment from 759 European and 274 Asian children. RESULTS: The prevalence of reported wheeze in the previous 12 months was higher among European (19.6%) than Asian children (11.9%), as was the prevalence of a night cough (European 64.2%, Asian 42.3%). Although the prevalence of diagnosed asthma was higher in European (12%) than Asian (6.2%) children, a slightly higher proportion of Asian than European children with current wheeze had visited their doctor (European 66.9%, Asian 78.1%, not significant) or been admitted to hospital for wheezing (European 4.8%, Asian 6.5%) in the previous 12 months. CONCLUSIONS: This study failed to demonstrate a higher prevalence of asthma among Asian than European children in Southampton. PMID- 1412097 TI - Platelet kinetics in asthmatic patients with and without aspirin intolerance. AB - BACKGROUND: A reduced platelet survival time has been described in asthmatic patients. There is also good evidence that platelets are involved in aspirin induced asthma. Since aspirin intolerant patients usually suffer from an active disease and often require anti-inflammatory treatment, it has been suggested that platelet survival time may be shorter in aspirin intolerant asthmatic subjects than in aspirin tolerant subjects. The objective of this study was to investigate this hypothesis. METHODS: Thirteen asthmatic subjects (six aspirin tolerant and seven aspirin intolerant) in a stable clinical condition and ten healthy subjects were studied. Platelet kinetics and survival time were measured with indium-111 labelled autologous platelets. RESULTS: Mean (SD) platelet sequestration ratios in the spleen and liver were lower in asthmatic (2.3 (0.9) and 0.6 (0.2) respectively) than in healthy subjects (3.2 (0.7) and 1.1 (0.4) respectively). However, mean (SD) platelet survival time in asthmatic subjects (8 (2.7) days) did not differ from that in healthy subjects (7.6 (1.1) days). No differences were observed in platelet kinetics between aspirin tolerant and aspirin intolerant patients. CONCLUSIONS: These results suggest the existence of an active non-splenic pool of platelets in patients with asthma. However, they failed to show platelet kinetic differences among asthmatic subjects with and without aspirin intolerance and do not support previous studies suggesting an altered platelet survival in stable asthma. PMID- 1412099 TI - Should we judge a mask by its cover? AB - BACKGROUND: A table of the approximate ranges of inspired oxygen delivered at given oxygen flow rates is often given on the packaging of oxygen masks. A study was carried out to check the inspired oxygen concentration given by one of the new masks, which has been designed to be used with or without the Venturi attachment as a result of the proposal to use it without the Venturi attachment as a general purpose mask for emergency use. METHODS: Measurements were made at resting respiratory rate and 26 breaths/min in 12 normal subjects. Continuous oxygen and carbon dioxide concentrations were recorded at the lips with a mass spectrometer, and inspired oxygen concentrations were calculated from end tidal values by means of the alveolar gas equation. Measurements were made at oxygen flow rates of 2, 4, and 6 l/min for the mask alone and at 2 and 4 l/min with both the 24% and the 28% Venturi attachments. RESULTS: Without the Venturi attachment the mask gave average inspired oxygen concentrations 8-10% greater than are stated on the packaging at oxygen flow rates of 2, 4, and 6 l/min at resting respiratory rates of 8-20 breaths/min, some individuals receiving 30% more than expected. Addition of the interchangeable Venturi attachments designed to give 24% and 28% inspired oxygen delivered average concentrations within 2% of the expected concentrations, no individual receiving more than 5% above the expected concentrations. CONCLUSIONS: The labelling on the packaging of oxygen masks may lead to inappropriate use by those not expert in prescribing oxygen therapy. Caution is still needed when a single multipurpose mask is being selected for emergency use, where accurate delivery of low concentrations of oxygen is vital for some patients. PMID- 1412098 TI - Asthma from birth to age 23: incidence and relation to prior and concurrent atopic disease. AB - BACKGROUND: Few studies present prospective data on the incidence of asthma. Its associations with sex and with prior and concurrent hay fever and eczema were examined in a nationally representative sample followed from birth to 23 years of age (British 1958 birth cohort). METHODS: Reports of asthma or wheezy bronchitis, hay fever and eczema were obtained by interview of parents of children at ages 7, 11, and 16 years, and of cohort members at age 23 years. Linked data from all four interviews were available on 7225 subjects (43% of the original birth cohort). RESULTS: The cumulative incidence of asthma or wheezy bronchitis was 18.2%, 21.8%, 24.5%, and 28.6% by the ages of 7, 11, 16, and 23 years respectively. Over the four incidence periods examined (0 to 7 years, 8 to 11 years, 12 to 16 years, 17 to 23 years) the average annual incidence of new cases was 2.6%, 1.1%, 0.71%, and 0.76% respectively. The male:female incidence ratio rose from 1.23 in the 0 to 7 year period to 1.48 at 12 to 16 years but had reversed to 0.59 at 17 to 23 years. A prior report of hay fever or eczema each increased the subsequent incidence of asthma or wheezy bronchitis by a factor of 1.7 to 2.0 independently of sex. This effect of prior atopic illness, however, was largely explained by the strong independent association of incidence of asthma and wheezy bronchitis with atopic disease at the end of each incidence period (odds ratios 2.0 to 2.5 per atopic condition, p < 0.01). CONCLUSIONS: Gender differences in the incidence of asthma or wheezy bronchitis vary with age and are not explained by atopy. The incidence of asthma or wheezy bronchitis can be predicted from a clinical history of hay fever or eczema but is more strongly associated with the presence of atopic disease at the time of onset. PMID- 1412100 TI - Rapid diagnosis of gram negative pneumonia by assay of endotoxin in bronchoalveolar lavage fluid. AB - BACKGROUND: Diagnosis of ventilator associated pneumonia can be made by quantitative cultures of bronchoalveolar lavage fluid or of protected specimen brushings, though cultures require 24-48 hours to provide results. In 80% of cases aerobic Gram negative bacteria are the cause. METHODS: A rapid diagnostic method of assessing the endotoxin content of lavage fluid by Limulus assay is described. Forty samples of lavage fluid were obtained from patients with multiple trauma requiring mechanical ventilation for a prolonged period. Pneumonia was diagnosed on the basis of clinical, radiological, and bacteriological findings, including quantitative cultures of lavage fluid. RESULTS: A relation was observed between the concentration of endotoxin in lavage fluid and the quantity of Gram negative bacteria. The median endotoxin content of lavage fluid in Gram negative bacterial pneumonia was 15 endotoxin units (EU)/ml; the range observed in individual patients was 6 to > 150 EU/ml. In patients with pneumonia due to Gram positive cocci and in non-infected patients the median endotoxin level was 0.17 (range < or = 0.06 to 2) EU/ml. An endotoxin level greater than or equal to 6 EU/ml distinguished patients with Gram negative bacterial pneumonia from colonised patients and from those with pneumonia due to Gram positive cocci. CONCLUSION: The measurement of endotoxin in lavage fluid is a rapid (less than two hours) and accurate diagnostic method. It should allow specific and early treatment of Gram negative bacterial pneumonia. PMID- 1412101 TI - Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease. AB - BACKGROUND: Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. METHODS: Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension < 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. RESULTS: No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). CONCLUSIONS: The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics. PMID- 1412103 TI - Endobronchial sonography: feasibility and preliminary results. AB - Endobronchial sonography, a new ultrasound technique, has been evaluated for the assessment of normal lungs and bronchial carcinomas. The procedure was performed with ultrasound catheters, which were introduced into central and peripheral bronchi through the operating channel of fibreoptic bronchoscopes. The bronchial wall is highly echogenic and laminated. The lung parenchyma appears echo rich and patchy. Pulmonary arteries can be identified by the pulsatile changes and floating echoes within the echo free lumen. Echo poor bronchial carcinomas were detected in 69 out of 74 patients with endoscopically visible tumours and in 19 out of 26 patients with peripheral carcinomas. The correct implantation of metallic stents was facilitated by endobronchial sonography in nine patients. The sonographic examination carried no particular risk and caused little discomfort. PMID- 1412102 TI - The pulmonary physician and critical care. 2. The injured lung: conventional and novel respiratory therapy. AB - Several alternatives to conventional ventilation in acute lung injury are now available and have been investigated to a varying degree. The assessment of all such techniques is limited by difficulties in designing proper comparative studies and by the time needed to recruit a large number of appropriate patients with acute lung injury. A common theme of lung volume maintenance combined with strategies designed to limit the extent of ventilator induced lung damage has emerged and should encourage reassessment of the conventional approach. The results of several large prospective comparative studies are eagerly awaited. Meanwhile we may reasonably suggest that improvements in respiratory support, together with advances in microbiological and pharmacological treatment, have the potential for improving the persistently disappointing survival rate in acute lung injury. PMID- 1412104 TI - Chronic necrotising pulmonary aspergillosis caused by Aspergillus niger in a mildly immunocompromised host. PMID- 1412105 TI - Neutrophilic alveolitis in Sweet's syndrome. AB - In a case of Sweet's syndrome (acute febrile neutrophilic dermatosis) neutrophilic alveolitis was found by lung biopsy. Pulmonary disease in this condition may be underrecognised yet, like the dermatological features, it responds rapidly to corticosteroids. PMID- 1412106 TI - Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case control study. PMID- 1412107 TI - Pleural abrasion: a new method of pleurodesis? PMID- 1412108 TI - Shunting through a patent foramen ovale. PMID- 1412109 TI - Persistent alveolar increased permeability to 99mTc DTPA in patients with advanced HIV infection. PMID- 1412110 TI - The management of tuberculous meningitis. PMID- 1412111 TI - Effects of corticosteroids in acute severe asthma. PMID- 1412112 TI - Corticosteroids in acute severe asthma: effectiveness of low doses. AB - BACKGROUND: Although the need for corticosteroids in acute severe asthma is well established the appropriate dose is not known. METHODS: The response to intravenous hydrocortisone 50 mg (low dose), 100 mg (medium dose), and 500 mg (high dose), administered every six hours for 48 hours and followed by oral prednisone, was compared in patients with acute asthma in a double blind randomised study. After initial emergency treatment with bronchodilators subjects received oral theophylline or intravenous aminophylline and nebulised salbutamol four hourly. Patients were given low, medium, or high doses of intravenous hydrocortisone and then 20, 40, or 60 mg/day respectively of oral prednisone with a reducing regimen over the following 12 days. Beclomethasone dipropionate, 400 micrograms twice daily by metered dose inhaler, was also started. Peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), and visual analogue dyspnoea scores (VAS) were recorded daily in hospital and PEF and VAS twice daily after discharge for a total of 12 days. RESULTS: The 66 subjects (40 female) who completed the study had a mean (SD) age of 31(14) years. On presentation mean (SD) FEV1% predicted in the low (n = 22), medium (n = 20), and high dose (n = 24) groups was 17(13), 19(12), and 19(11) and after emergency bronchodilator treatment 32(20), 30(12), and 36(13). After 24 hours of treatment the respective post-bronchodilator FEV1% predicted values were 62(22), 62(23), and 65(28) compared with 71(24), 69(22), and 71(24) after 48 hours. No significant difference between the groups was detected. PEF and VAS improved with treatment over the 12 days but was not influenced by steroid dose. CONCLUSIONS: Hydrocortisone 50 mg intravenously four times a day for two days followed by low dose oral prednisone is as effective in resolving acute severe asthma as 200 or 500 mg of hydrocortisone followed by higher doses of prednisone. PMID- 1412113 TI - Controlled trial of intravenous corticosteroids in severe acute asthma. AB - BACKGROUND: The value of corticosteroids in severe acute asthma continues to be debated. METHODS: Ninety consecutive patients admitted to the emergency room with severe acute asthma were studied in a randomised, double blind, controlled trial to determine the efficacy of corticosteroids. Eighty two patients completed the study. All received oxygen therapy and intensive bronchodilator treatment. The patients were divided into three groups for steroid treatment, receiving intravenous methylprednisolone 10 mg/kg every four hours for 48 hours (29 patients, group A); intravenous methylprednisolone 2 mg/kg every 4 hours for 48 hours (27 patients, group B); or no intravenous corticosteroids (26 patients, group C). RESULTS: There were no differences on admission among the three groups in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), or arterial oxygen or carbon dioxide tension; and the rates of recovery in FEV1, FVC, and PEF were similar. CONCLUSIONS: Corticosteroids given with bronchodilators have not shown a beneficial effect in the first 48 hours of recovery of severe acute asthma. Only in those patients who failed to respond by the third hour of treatment, and in those who were previously taking oral corticosteroids, does a favourable, though not statistically significant, effect appear to occur. PMID- 1412114 TI - Attenuation of exercise induced asthma by local hyperthermia. AB - BACKGROUND: Prior treatment with local hyperthermia has been shown to prevent mast cell degranulation and leucocyte histamine release, and to reduce mortality and cellular infiltrates in a model of acute lung injury. Local hyperthermia is effective in reducing the symptoms of the common cold and perennial and seasonal allergic rhinitis, nasal patency also being improved in rhinitis. It is possible that these effects are mediated by common anti-inflammatory mechanisms, and that this treatment may be effective in the treatment of asthma. The effect of prior local hyperthermia on the response to exercise challenge and histamine bronchoprovocation was therefore examined. METHODS: In a randomised, double blind, placebo controlled, crossover study, 10 asthmatic subjects with exercise induced asthma used machines delivering 40 1/minute of fully humidified air at either 42 degrees C (active treatment) or 31 degrees C (placebo treatment) for 30 minutes' tidal breathing. For each pretreatment, at two week intervals they underwent exercise challenges starting one and 24 hours after starting the inhalations. After a further two weeks the protocol was repeated with histamine substituted for the exercise challenges. RESULTS: The mean (SE) maximum percentage fall in forced expiratory volume in one second (FEV1) was significantly lower one hour after treatment with air at 42 degrees C (30.8% (3.1%)) than after treatment with air at 31 degrees C (22.3% (2.9%)). There was no significant effect on exercise challenge at 24 hours, or on histamine challenge at either time point, though there were nonsignificant trends towards protection with exercise at 24 hours and with histamine at one hour. CONCLUSION: In asthmatic subjects the response to exercise challenge is significantly attenuated one hour after treatment with local hyperthermia. This treatment warrants further investigation in the treatment of clinical asthma and other inflammatory disorders. PMID- 1412115 TI - Controlled trial of respiratory muscle training in chronic airflow limitation. AB - BACKGROUND: Whether respiratory muscle training is of benefit to patients with chronic airflow limitation is controversial. The objective of the study was to determine the effect of resistance breathing training on physiological and functional measures in patients with chronic airflow obstruction. METHODS: The design was a randomised, double blind, controlled trial with a six month follow up. Eighty two patients with a forced expiratory volume in one second (FEV1) of less than 70% predicted, and an FEV1/vital capacity ratio of less than 0.7, were randomised to receive training for 10 minutes five times daily with progressively larger resistances through a resistive breathing device (PFLEX) as tolerated or to a sham device which gave minimal resistance. The main outcome measures, respiratory muscle strength and endurance, a progressive exercise test, a six minute walk test and physical and emotional function (chronic respiratory questionnaire) were assessed at monthly intervals. Patients in both groups were also randomised to wear or not wear nose clips during their training. RESULTS: No significant differences were observed between treatment and control groups, with or without nose clips, for any of the outcomes. Confidence intervals on the difference between treatments were narrow, excluding clinically important difference in any major outcome. CONCLUSION: This training regimen fails to strengthen respiratory muscles or improve exercise or functional capacity in patients with chronic airflow limitation. PMID- 1412117 TI - Variability of inspired oxygen concentration with nasal cannulas. AB - BACKGROUND: The likely values of inspired oxygen concentration (FIO2) of patients with chronic obstructive pulmonary disease breathing via nasal cannulas have not been assessed previously. METHODS: Seven patients with chronic obstructive lung disease and seven healthy subjects were studied while breathing oxygen via nasal cannulas or fixed performance (Venturi) or uncontrolled (MC) oxygen masks. Breath to breath values of FIO2 were calculated by extrapolation from expired oxygen and carbon dioxide concentrations on the basis of the oxygen-carbon dioxide relationship and on the assumption of a respiratory exchange ratio (R) of 0.8. RESULTS: In both groups of subjects the average values of FIO2 with nasal cannulas at 1 and 2 l min-1 were of a similar order to those achieved with 24.5% and 28% Venturi masks, but variations within and between subjects in both groups breathing via nasal cannulas were considerable and similar to those found with MC masks. In the seven patients with chronic obstructive lung disease breathing via nasal cannulas at 2 l min-1 the average FIO2 varied from 23.7% to 34.9%. CONCLUSIONS: "Typical" values of FIO2 quoted with nasal cannulas can mislead. The results confirm that this mode of oxygen delivery is unsatisfactory if precise control of inspired oxygen is desired. PMID- 1412116 TI - Integrity of the alveolar-capillary barrier and alveolar surfactant system in smokers. AB - BACKGROUND: The permeability of the alveolar-capillary barrier to technetium-99m labelled diethylenetriamine pentaacetate (99mTc DTPA) is known to be greatly increased in smokers, but the underlying mechanism is poorly understood. Abnormal permeability of the alveolar epithelium as well as impaired surfactant function has been suggested. The purpose of this study was to examine transudation of urea and albumin into the alveoli and alveolar surfactant function in smokers and non smokers and to relate these variables to the rate of alveolar-capillary transfer of 99mTc DTPA. METHODS: Standardised bronchoalveolar lavage was performed and the yield of urea and albumin measured in the lavage fluid. The integrity of the alveolar surfactant system was assessed by measurement of the surface activity and of the yield of phospholipids in alveolar lavage fluid. RESULTS: The mean decay constant for the pulmonary clearance of 99mTc DTPA was 0.028/min in the smokers and 0.009/min in the non-smokers. The recovery of albumin and urea in alveolar lavage fluid was very similar in the two groups. The surface activity of alveolar lavage fluid was lower in smokers than in non-smokers (minimum surface tension 37.9 versus 28.6 mN/m) and the yield of phospholipids was reduced (2.08 versus 3.86 mg). The rate constant for the pulmonary clearance of 99mTc DTPA correlated with the yield of phospholipids at bronchoalveolar lavage. CONCLUSIONS: The study shows that increased alveolar-capillary transfer of 99mTc DTPA in smokers is not accompanied by increased transudation of small or large molecules into the alveoli. The findings support the hypothesis that increased clearance of 99mTc DTPA in smokers is related to surfactant dysfunction. PMID- 1412118 TI - Induction of sleep apnoea with negative pressure ventilation in patients with chronic obstructive lung disease. AB - BACKGROUND: Negative pressure ventilation provides intermittent non-invasive ventilatory assistance for patients with advanced chronic obstructive lung disease. Upper airway obstruction during sleep, a reported complication of the technique, may, however, limit its clinical applicability. METHODS: The effects of nocturnal negative pressure ventilation on ventilation and on indices of sleep quality were investigated in five patients with severe chronic obstructive lung disease (mean (SE) FEV1 31% (3%) predicted) who had completed three months of nightly negative pressure ventilation. Subjects underwent overnight polysomnography on consecutive nights, the first night serving as a control and negative pressure ventilation being provided on the second night. Ventilators were adjusted to result in maximum suppression of the peak phasic electromyogram signal from the diaphragm. RESULTS: Negative pressure ventilation resulted in substantial increases in episodes of obstructive apnoea and hypopnoea (mean (SE)/h 59.3 (19.8) v 3.2 (1.3) on control nights). Most obstructive events, however, were associated with under 3% oxygen desaturation, and the lowest recorded values for overnight oxygen saturation were similar on the two study nights. Negative pressure ventilation was also associated with significant increases in the frequencies of movement arousals and changes in sleep stage. CONCLUSIONS: Negative pressure ventilation applied during sleep to patients with advanced chronic obstructive lung disease may result in the development of recurrent episodes of apnoea and hypopnoea as well as altered sleep quality, which could limit its clinical applicability. PMID- 1412119 TI - Effects of corticosteroids on bronchodilator action in chronic obstructive lung disease. AB - BACKGROUND: Short term treatment with corticosteroids does not usually reduce airflow limitation and airway responsiveness in patients with chronic obstructive lung disease. We investigated whether corticosteroids modulate the effects of inhaled salbutamol and ipratropium bromide. METHODS: Ten non-allergic subjects with stable disease were investigated; eight completed the randomised, double blind, three period cross over study. Treatment regimens consisted of 1.6 mg inhaled budesonide a day for three weeks, 40 mg oral prednisone a day for eight days, and placebo. After each period cumulative doubling doses of salbutamol, ipratropium, a combination of salbutamol and ipratropium, and placebo were administered on separate days until a plateau in FEV1 was reached. A histamine challenge was then performed. RESULTS: At the end of placebo treatment mean FEV1 was 55.5% predicted after inhaled placebo, 67.9% predicted after salbutamol and 64.0% predicted after ipratropium. Compared with the results after the placebo period the FEV1 with salbutamol increased by 0.7% predicted after treatment with budesonide and by 0.7% predicted after treatment with prednisone; the FEV1 with ipratropium increased by 0.7% predicted after budesonide and by 4.8% predicted after prednisone; none of these changes was significant. After placebo treatment the geometric mean PC20 was 0.55 mg/ml after placebo, 1.71 mg/ml after salbutamol and 0.97 mg/ml after ipratropium. Compared with the placebo period the PC20 with salbutamol was increased by 0.86 doubling concentrations after treatment with budesonide, and by 0.67 doubling concentrations after prednisone; the PC20 with ipratropium increased by 0.03 and 0.34 doubling concentrations after budesonide and after prednisone respectively compared with placebo; none of these changes was significant. CONCLUSIONS: In non-allergic subjects with chronic obstructive lung disease short term treatment with high doses of inhaled or oral corticosteroids does not modify the bronchodilator response to salbutamol or ipratropium or the protection provided by either drug against histamine. Salbutamol produces greater protection from histamine induced bronchoconstriction than ipratropium. PMID- 1412120 TI - Nilutamide pneumonitis: a report on eight patients. AB - BACKGROUND: Nilutamide is a new, specific synthetic antiandrogen, released in several countries for the treatment of metastatic carcinoma of the prostate. Eight patients at the University Medical Centre at Dijon and affiliated referring hospitals developed reversible pulmonary opacities and respiratory symptoms while taking the drug. METHODS: Records of eight patients who developed new, otherwise unexplained chest opacities while taking nilutamide were reviewed. In each patient a careful aetiological search was made for other environmental or endogenous causes. Six patients underwent bronchoalveolar lavage, and lavage fluid was cultured. Corticosteroids were not given, unless gas exchange was compromised (two patients). RESULTS: The eight patients (all male) had had carcinoma of the prostate diagnosed on average 10.2 months earlier. All had improved with nilutamide, with a dramatic decrease of prostate specific antigen levels. Seven had received nilutamide at the recommended dosage of 150 mg/day, and one had received twice that amount. Treatment had lasted on average 113 (range 10-225) days, and the mean cumulated exposure was 21.8 (3-38) grams. The chest radiographs showed bilateral infiltrates, with no consistent topographic predilection. A restrictive lung defect was present in six patients and hypoxia in all (mean arterial oxygen tension (PaO2) 6.6 kPa). Bronchoalveolar lavage showed lymphocytosis in four patients and neutrophilia in two. The outcome was favourable in all patients after they had stopped nilutamide only (five patients), with corticosteroids (two patients) or a simple reduction of nilutamide from 300 to 150 mg/day (one patient). Recovery was associated with improvement of pulmonary function and PaO2. CONCLUSION: Nilutamide is associated with interstitial pneumonitis in about 1% of patients and appears reversible. PMID- 1412121 TI - Acute pneumonitis associated with low dose methotrexate treatment for rheumatoid arthritis: report of five cases and review of published reports. AB - BACKGROUND: Low dose methotrexate has become established in the treatment of refractory rheumatoid arthritis. Until recently it has been considered that the use of a low dose regimen (< 20 mg/week) would avoid the pulmonary toxicity associated with the higher doses prescribed in malignant disease. Although initial experience with low dose methotrexate was encouraging, an increasing number of cases of an acute, life threatening pneumonitis are being reported in patients with refractory rheumatoid arthritis. PATIENTS: Since 1984 43 patients with refractory rheumatoid arthritis have been established on low dose methotrexate in the Oxford Health District. Five of these patients have subsequently developed acute methotrexate induced pneumonitis. The clinical and radiological features of these cases are described and previous reports reviewed. RESULTS: Five patients having low dose methotrexate treatment developed acute pneumonitis. Presentation was subacute and dominated by constitutional features. Respiratory symptoms developed insidiously but progressed rapidly with increasing dyspnoea associated with severe hypoxia. Chest radiographs were non-specific, showing diffuse interstitial infiltration and alveolar shadowing. Microbiological investigation gave negative results. In all cases methotrexate was discontinued and high dose corticosteroids started, with rapid clinical and radiological improvement. After withdrawal of steroid both clinical and radiological resolution was maintained at follow up. CONCLUSION: Acute pneumonitis is an uncommon but serious adverse effect of low dose methotrexate treatment for refractory rheumatoid arthritis. The initial presentation is non-specific and a high index of suspicion is required as respiratory failure may develop rapidly. Management depends on exclusion of infection, withdrawal of methotrexate, and high dose corticosteroid treatment. Full supportive treatment is indicated as the prognosis in such patients is good. PMID- 1412122 TI - Effect of heparin on pulmonary fibroblasts and vascular cells. AB - BACKGROUND: There is a large increase in mast cell numbers in fibrotic lung tissue, suggesting that mast cells may play a part in the pathogenesis of pulmonary fibrosis. Glycosaminoglycans, such as heparan sulphate, that are structurally related to heparin (a mast cell product) are part of the extracellular matrix and known to regulate cell growth. Basic fibroblast growth factor is a heparin binding growth factor produced by endothelial cells. METHODS: A study was carried out to examine the effect of heparin, basic fibroblast growth factor, and mast cell products on the proliferation of normal human lung fibroblasts and the effect of adding heparin on the proliferation of lung fibroblasts and pulmonary vascular cells incubated with basic fibroblast growth factor. RESULTS: Heparin at low concentration (0.03, 0.3-1.0 micrograms/ml) stimulated the proliferation of normal human lung fibroblasts in culture whereas a higher concentration (100 micrograms/ml) had an inhibitory effect. Mast cell products also stimulated the proliferation of fibroblasts, and the effect was decreased by pretreatment with heparinase or protamine. Heparin enhanced the growth of both fibroblasts and pulmonary vascular cells induced by low concentrations of basic fibroblast growth factor. CONCLUSIONS: Mast cells in fibrotic lung tissue may regulate fibroblast proliferation by releasing heparin. These results suggest that endothelial cells may interact with mast cells and modulate fibroblast growth by release of basic fibroblast growth factor. PMID- 1412123 TI - High resolution computed tomographic assessment of asbestosis and cryptogenic fibrosing alveolitis: a comparative study. AB - BACKGROUND: The aim of this study was to compare the distribution and configuration of lung opacities in patients with cryptogenic fibrosing alveolitis and asbestosis by high resolution computed tomography. METHODS: Eighteen patients with cryptogenic fibrosing alveolitis and 24 with asbestosis were studied. Two independent observers assessed the type and distributions of opacities in the upper, middle, and lower zones of the computed tomogram. RESULTS: Upper zone fibrosis occurred in 10 of the 18 patients with cryptogenic fibrosing alveolitis and in six of the 24 patients with asbestosis. A specific pattern in which fibrosis was distributed posteriorly in the lower zones, laterally in the middle zones, and anteriorly in the upper zones was seen in 11 patients with cryptogenic fibrosing alveolitis and in four with asbestosis. Band like intrapulmonary opacities, often merging with the pleura, were seen in 19 patients with asbestosis but in only two with cryptogenic fibrosing alveolitis. Areas with a reticular pattern and a confluent or ground glass pattern were the commonest features of cryptogenic fibrosing alveolitis (15 and 14 patients respectively) but were uncommon in asbestosis (four and three patients). Pleural thickening or plaques were seen in 21 patients with asbestosis and in none with cryptogenic fibrosing alveolitis. CONCLUSION: Apart from showing pleural disease high resolution computed tomography showed that confluent (ground glass) opacities are common in cryptogenic fibrosing alveolitis and rare in asbestosis whereas thick, band like opacities are common in asbestosis and rare in cryptogenic fibrosing alveolitis. PMID- 1412125 TI - An expansible cannula: a new technique for chest drain insertion. AB - The insertion of a chest drain into the pleural space is a common procedure used by many specialties. The commonly used device is a prepacked, sterile plastic tube with its own central metal trocar. Complications may arise during its insertion, with the occasional penetration of intrathoracic and upper abdominal organs. As most chest drains are inserted by junior and relatively inexperienced doctors, it is therefore imperative that a simple, safe, and effective technique of insertion is found. A device has been developed that consists of a 5 cm conical length of an expansible cannula, made from rolled metal foil, which when inserted into the chest reaches only a few millimetres within the pleura. When an expander tube, 10 mm in diameter, is passed through the device from its proximal end the conical tube is distended into a hollow cylindrical one, through which a standard Portex chest catheter is passed. The whole appliance is then removed over the end of the tube, leaving the drain in situ. The efficacy of this unique device has been tested in a pilot study in 22 patients. There have been no complications. PMID- 1412124 TI - The pulmonary physician and critical care. 3. Pharmacotherapy in lung injury. PMID- 1412126 TI - Recurrent respiratory obstruction from a mediastinal bronchogenic cyst. AB - A large mediastinal bronchogenic cyst presented acutely with paroxysmal atrial fibrillation and severe airflow obstruction. The patient had experienced identical symptoms on two other occasions over the previous 24 years. These had been previously misdiagnosed as due to a mediastinal lymphoma. Percutaneous extrapleural aspiration successfully decompressed the cyst with substantial improvement in lung function. Recurrent swelling of the cyst occurred that could not be relieved surgically. After repeat aspiration percutaneous instillation of bleomycin and alcohol has been used to prevent further increase in the size of the cyst. PMID- 1412127 TI - Treatment of desmoid tumours in Gardner's syndrome. AB - A 24 year old woman with Gardner's syndrome developed a massive chest wall desmoid tumour, which required radical excision and prosthetic reconstruction. In view of the local aggressiveness of this tumour and the fact that it does not metastasize a policy of radical surgery when possible is recommended. PMID- 1412128 TI - Endobronchial actinomycosis mimicking pulmonary neoplasm. AB - A 60 year old man had recurrent pneumonia. Bronchoscopy disclosed a necrotic mass in the left lower lobe bronchus, which histological examination showed to contain sulphur granules. The endobronchial mass had disappeared by the second bronchoscopy one week later. The patient was treated with penicillin for one year and was cured. Actinomycosis must be included in the differential diagnosis of an endobronchial mass. PMID- 1412129 TI - Barcelona's asthma epidemics. PMID- 1412130 TI - Cellular mechanisms of acute lung injury: implications for future treatment in the adult respiratory distress syndrome. PMID- 1412131 TI - [Physiology of the digestive smooth muscle]. AB - By comparison with striated muscle, the main features of digestive smooth muscle are richness, complexity and diversity specially with thanks to the enteric and prevertebral nervous neurons which add up their effects to those of the central nervous system. The morphological and molecular characteristics of the smooth muscle contractility begin to be unveiled, but a lot of basic knowledge is still needed for further pharmacological advances. PMID- 1412132 TI - [Methods for studying the motility in the small intestine, colon and recto-anal area]. AB - Small bowel and colonic motility can be studied either indirectly by the determination of the transit time or directly in recording bowel contractions. Small bowel transit time is usually assessed with the H2-breath test when colonic transit time is mainly determined fluoroscopically in studying the progression of radiopaque markers along the large bowel. Scintigraphic techniques are promising but not routinely used techniques. In the small bowel, gut contractions are recorded with manometric probes. To study colonic movements, electromyography is more usual than manometry. In both cases, whatever the technique employed, the large inter- and intra (topographic and nycthemeral) variability need to be considered for the interpretation of the motor patterns. Rectoanal studies led to consider two aspects: how the rectum acts as a reservoir and anal function. The ability of the rectum to be a reservoir is assessed either by the volume remaining in the rectum during the rectal perfusion with saline or by the determination of the maximal tolerable volume of distension. Manometry and/or electromyography test anal function at rest and during a rectal distension, straining or a voluntary contraction. PMID- 1412133 TI - Experimental models to evaluate the effects of drugs on digestive motility. PMID- 1412134 TI - [Study methods in clinical pharmacology of the upper digestive tract (esophagus, stomach)]. PMID- 1412135 TI - [Endoscopic evaluation of the effect of low-dose ketoprofen, ibuprofen and aspirin on the gastric mucosa in man]. PMID- 1412136 TI - [Successful treatment of ocular candidiasis with fluconazole]. PMID- 1412137 TI - [Protection with misoprostol of gastric mucosa lesions induced by aspirin. Measurement of the difference in transgastric potential]. PMID- 1412138 TI - Assessment of the efficacy of vasodilator drugs in peripheral vascular disease through a study of skeletal muscle metabolism using 31P nuclear magnetic resonance (NMR) spectroscopy. PMID- 1412139 TI - Insulin action in cirrhosis. The importance of protein-energy malnutrition. PMID- 1412140 TI - [Evaluation criteria for protocols submitted to the consultant committee for protection of persons in biomedical research (CCPPRB) Lyon-C]. AB - In order to fulfill its task, the Lyon-C institutional review board (CCPPRB) developed standards for the evaluation of clinical research protocols. This check list envisages 1- the mandatory documents in the absence of which the protocol will not be considered, 2- scientific quality standards, 3- ethical quality standards. An agreement on the use of such standards in France might improve the functioning of institutional review boards (CCPPRB) and the quality of clinical research. PMID- 1412141 TI - [Double blind study of the efficacy of mebendazole in minor forms of human toxocariasis]. AB - The authors discuss the results of a double-blind, placebo-controlled, randomised study on the efficacy of mebendazole versus placebo in the treatment of human toxocariasis in 45 and 43 patients respectively, who exhibited evocative clinical and biological symptoms and a seropositivity. Scores were used to quantify clinical (20 parameters) and biological (blood count, sedimentation rate, determination of total and anti-Toxocara IgE, serodiagnosis by immunoelectrophoresis) abnormalities. The reassessment were done 1 month after the end of treatment. Analyzing the results showed a similar efficacy of mebendazole and placebo on the score of clinical signs; the score of biological abnormalities was significantly reduced in mebendazole group, but the serodiagnosis by immunoelectrophoresis was the only parameter that was significantly normalized. These results corroborate previous prospective studies and allow to make a conclusion in favour of a moderate efficacy of mebendazole. PMID- 1412142 TI - [Parkinson disease in neurologic general practice in Alsace-Lorraine. Characteristics and study of the treatment]. AB - A study was performed in 220 out-patients with Parkinson's disease followed by general neurologists. The general characteristics of the patients are similar to those observed in the large epidemiological studies. The main conclusion concerns the low use of dopamine agonists. It confirms the discrepancy between drug prescription in general practice and the data from therapeutic drug trials. PMID- 1412143 TI - [Physiological and clinical recall on equilibrium disorders]. AB - Static and dynamic equilibrium (posture and gait) is indispensable for a normal behavior in human. Its mechanisms are nearly the same in superior species and in man, but humans are the only ones to have acquired exclusively biped upright position and gait. Equilibrium is a sensory function involving 3 sub systems: visual, vestibular and sensori-motor (proprioceptive), controlled by cerebellum and cerebral structures. Information coming from those 3 sub systems must be concordant. In case of discordance, the patient is in a state of sensory conflict. This conflict can induce disequilibrium or true vertigo. After a recall on equilibrium, the authors report the results of an epidemiologic study upon 5298 patients suffering of balance disorders and treated by an alpha-blocker: nicergoline (30 mg/day during 6 months). PMID- 1412144 TI - [Extended worldwide experience. HMG-CoA reductase inhibitors: lovastatin and simvastatin]. AB - Lovastatin and simvastatin are the first licensed compounds of a potent new class of lipid lowering drugs whose mechanism of action is to inhibit HMG-CoA reductase, a rate-limiting enzyme in the cholesterol biosynthetic pathway in the liver. Inhibition of cholesterol synthesis leads to upregulation of LDL-receptors in the liver and subsequent increased LDL clearance. Both agents are pro-drugs (lactones) which undergo extensive first-pass hepatic metabolism to the beta hydroxyl acid form. These drugs are liver specific and have low systemic exposure as open-acid forms (plasma concentration < 5% of oral dose). Thus, theoretically both drugs have low potential for systemic adverse events. They are potent and effective agents for the treatment of primary hypercholesterolemia. The adverse experiences reported for both drugs demonstrate an excellent safety profile. PMID- 1412145 TI - Carbamazepine, fluvoxamine. Is there a pharmacokinetic interaction? PMID- 1412146 TI - [Rhabdomyolysis associated to fenoverin therapy and complicated by acute renal failure]. PMID- 1412148 TI - [Pharmacology of gastric antisecretory agents and of modifying drugs of the digestive motility. Current methodological developments; introductory discussion]. PMID- 1412147 TI - [Thrombopenia induced by pipemidic acid]. PMID- 1412149 TI - Pharmacological assessments of antisecretory drugs in man. The role of intragastric pHmetry. PMID- 1412150 TI - [In vitro evaluation of antacid activity in gastric acid secretion in static and dynamic systems]. AB - A valid in vitro evaluation of antacid capacity should consider: 1) the intragastric pH-range; 2) the antacid mechanism; 3) the dependence of antacid activity from intraluminal flux variations; 4) the interaction between proteins and antacids. Pharmacologically, a static method allows 1) to quantify H+ binding sites at different pH-end points of the titration: pH 3.0, 2.0 and 1.0 and 2) to characterize the antacid mechanism, neutralizing activity and/or buffering capacity. In dynamic conditions, using the "artificial stomach-duodenum" model the antacid-induced resistance to acidification was measured, the antacid mechanisms were characterized in regard to intraluminal gastroduodenal flux variations and the incidence of antacid activity on duodenal pH was evaluated. These procedures were applied to antacid evaluation of proteins, as natural antacids, and of drugs containing aluminium salts alone or combined with magnesium salts. Pharmacologically, antacid drugs exhibited a greater amount of H+ binding sites when titration end-point was pH 1.0 than pH 3.0 corresponding to the development of neutralizing activity and/or buffering capacity. In dynamic conditions, the drugs, like proteins, induced a potent resistance to acidification related to gastric emptying fluxes. Antacid effect was supported by neutralizing activity and/or by buffering capacity. It was prolonged by removal of H+ ions since lagtimes for recovering initial pH were longer than antacid total emptying, the dilution of intragastric content by H+ impoverished secretory flux contributing thus to prevent gastric acidification. At duodenal site, proteins and aluminium-containing antacids induced the same duodenal pH as controls, without antacids, while magnesium-containing antacids increased it. PMID- 1412151 TI - Peritoneal fluid and plasma fibrinolytic activity in women with pelvic inflammatory disease. AB - Previous studies have shown that the fibrinolytic activity of peritoneum is depressed in local inflammation. We measured fibrinolytic parameters in peritoneal fluid and in plasma of 10 women with pelvic inflammatory disease (PID). Nine women, in whom laparoscopy for sterilisation was performed, served as a control group. In the peritoneal fluid of women with PID, PAI-Ag, t-PA-Ag and u PA-Ag were many times higher than in the control group. In contrast to the antigens which may be present in inert complexes, the potentially active compounds, measured as t-PA activity and plasmin-activable scu-PA, were not significantly different in the two groups, and in none of the samples was the active enzyme tcu-PA detectable. Nevertheless, the mean peritoneal fluid TDP and FbDP concentrations were about twenty times higher in the PID group than in the control group. In plasma of PID patients, none of the parameters except u-PA-Ag differed from those in the control group. The difference between control and patient plasma u-PA-Ag was statistically significant, but too small to attach any relevance to the observation. Our data suggest that, in contrast to the classical concept of decreased fibrinolytic activity as a cause of adhesion formation, intraperitoneal fibrinolysis is enhanced in peritoneal inflammation through stimulation of the local production of t-PA and u-PA. Despite concomitant production of PAI, fibrinolysis occurs at a high rate, resulting in high levels of fibrin degradation products. Since this activated fibrinolysis does not meet the demand, therapeutic enhancement should be considered to prevent adhesions. PMID- 1412152 TI - Desmopressin has no beneficial effect on excessive postoperative bleeding or blood product requirements associated with cardiopulmonary bypass. AB - Cardiopulmonary bypass during open-heart surgery is sometimes associated with excessive perioperative bleeding. Following a non-randomized study suggesting that desmopressin acetate (desmopressin) reduced blood product requirements in these patients, we conducted a double-blind, placebo-controlled randomized trial of desmopressin (0.3 micrograms/kg, i. v.) in 92 patients with overt bleeding and a prolonged bleeding time. Mean blood loss during the first 24 h post-treatment was similar in the desmopressin and placebo groups (582 vs 465 ml, respectively; p = 0.15). Red-cell (p = 0.76), fresh frozen plasma (r = 0.66) and platelet unit (p = 0.74) requirements were also similar. The haemostatic effect of desmopressin has been attributed to the release of von Willebrand factor (vWF) and a reduced bleeding time. In our study, vWF and factor VIII:C levels increased while the bleeding time decreased significantly at 90 min and 24 h in both groups and, although vWF and factor VIII:C levels were slightly higher in desmopressin treated patients at 90 min, the difference was not significant. Thrombin antithrombin III complex, fibrinogen degradation product and tissue plasminogen activator levels, reflecting activation of the coagulation and fibrinolytic systems, respectively, decreased uniformly in both groups. We conclude that desmopressin is not useful in reducing blood loss or blood product requirements in patients with excessive immediate postoperative bleeding. PMID- 1412153 TI - Monocyte tissue factor expression induced by Plasmodium falciparum-infected erythrocytes. AB - Monocytes are active elements of the host response against Plasmodium falciparum. They are able to express tissue factor and trigger the extrinsic pathway of blood coagulation the activation of which remained unclear in malaria. Our aim was to assess the tissue factor expression of purified blood monocytes stimulated by cultured Plasmodium falciparum-infected erythrocytes. Malaria parasite induced an early generation of tissue factor with a peak between 8 and 12 h of stimulation. Maximum expression was observed for parasitemia ranging from 1 to 2%. Plasmodium falciparum culture supernatants had the same effect showing the existence of a soluble factor able to induce the tissue factor expression. These data, demonstrating an activation of the tissue factor pathway by the malaria parasite, emphasize thrombin generation. Therefore, thrombin could participate in malaria pathology either in the microcirculatory blockade via platelet and fibrinogen activation or as a mitotic. PMID- 1412154 TI - A collaborative study on the measurement of protein S antigen in plasma. AB - A collaborative study on the measurement of protein S (PS) antigen (total and free) in a freeze-dried ampouled test plasma by assay against local house standard plasmas was carried out in eleven laboratories. Potency estimates of total PS showed good agreement between laboratories with a geometric coefficient of variation (gcv) of 5.9% and an overall combined potency of 0.84 units per ml. Potency estimates of free PS antigen in the test sample were associated with increased variability between laboratories resulting from the polyethylene glycol (PEG) precipitation step which is used to separate free PS from PS bound to the C4b binding protein. Free PS in the test could be expressed relative to either total PS in the house standards (e.g. 0.28 units per ml) or relative to free PS in the house standards following PEG precipitation (e.g. 0.71 units free PS per ml). PMID- 1412155 TI - High level expression of active human prothrombin in a vaccinia virus expression system. AB - We have worked out an efficient and time saving procedure for the expression of recombinant human prothrombin. The glycoprotein was expressed in the vaccinia virus expression system in several mammalian cell lines. The kidney cell lines Vero and BHK and the human cell line Hela were found to efficiently secrete prothrombin. Expression level of 3-4 micrograms of factor II per 10(6) cells per day corresponding to 18-23 mU per 10(6) cells per day were achieved. Since the expression levels obtained with the vaccinia virus/Vero cell system were comparable to those obtained in amplified transformed CHO cells it provides an alternative system for the efficient expression of human prothrombin and may allow to further elucidate structure-function relationships of (pro)thrombin and its various effectors. PMID- 1412156 TI - Inhibition by D-MePhe-Pro-Arg-H (GYKI-14766) of thrombus growth in experimental models of thrombosis. AB - The antithrombotic action of the highly effective synthetic thrombin inhibitor D MePhe-Pro-Arg-H (GYKI-14766) was studied in various models of experimental thrombosis. The compound administered to rats and rabbits by i.v. bolus injections, continuous i.v. infusions, subcutaneously and orally, respectively, induced significant decrease in thrombus weight (i) in a quantitative venous thrombosis model with stasis based on vascular lesion in rats, (ii) in an extracorporeal arterio-venous shunt model in rabbits, and (iii) prevented the occlusion of the vessel in arterial thrombosis induced by mechanical damage in rats. By using the arterio-venous shunt model in rabbits the inhibitory effect on thrombus growth could be demonstrated as a function of dose and time in self controlled experiments. Blood level of the inhibitor determined by a bioassay varied between 0.09-0.67 microgram/ml whole blood when doses of 15 and 20 mg/kg were administered orally. A correlation was found between thrombin time, platelet aggregation induced by thrombin ex vivo and the weight of thrombi formed. PMID- 1412157 TI - The consumption of antithrombin III during coagulation, its consequences for the calculation of prothrombinase activity and the standardisation of heparin activity. AB - The decay rate of thrombin in plasma is shown to be linearly proportional to the concentration of antithrombin III (AT III), not only in the absence but also in the presence of heparin. This is a consequence of partitioning of heparin between AT III and other plasma proteins. In previous articles were calculated the prothrombin converting activity assuming a fixed concentration of AT III. Since AT III is consumed during the clotting process, prothrombinase activity is more accurately approximated using an algorithm that counts with the decrease of the AT III concentration. It is shown this leads to higher prothrombinase activities. The (absence of) inhibition of prothrombin conversion by prothrombinase in the presence of heparins found with the previous method is also found using the new algorithm. From the results presented it is evident that characteristic parameters of heparin action have to be normalised to the AT III concentration. On this basis we define a Standard Independent Unit of the antithrombin activity of heparin. PMID- 1412158 TI - Insights on monoclonal antibodies to kininogens' heavy chain which influence kininogens' binding to platelets. AB - Purified domains of low molecular weight kininogen (LK) can be used directly to determine the epitopes of monoclonal antibodies (mAbs) that have been shown to influence kininogen function. LK, purified from plasma by carboxymethyl-papain Sepharose 4B affinity chromatography and kaolin adsorption, was digested by trypsin and chymotrypsin. The domains of LK were then separated by gel filtration followed by carboxymethyl-papain-Sepharose 4B affinity chromatography. Using the purified domains of LK's heavy chain, the regions on kininogens' heavy chain which various monoclonal antibodies are directed to were determined by enzyme linked immunosorbent assay and immunoblotting. MAb 2B5 which neutralized kininogens' ability to inhibit calpain cross-reacted with domains 2 and 3. MAb HKH8 which reacted with kininogens' domain 1 and 2 was found to inhibit 125I-HK binding to platelets. At two-fold molar excess, mAb HKH8 was a better inhibitor of 125I-HK binding to platelets than higher concentrations, where the antibody was shown to cause increased binding to platelets. Alternatively, HKH8 F(ab')2 completely inhibited 125I-HK binding to platelets even at high concentrations of antibody. These studies indicate that purified domains of kininogens' heavy chain can be used to rapidly localize epitopes for antibodies. Further, mAb HKH8 should be a valuable probe to understand the mechanisms of kininogens' binding to platelets. PMID- 1412159 TI - Multicenter evaluation of three commercial methods for measuring protein S antigen. AB - This collaborative study was designed to assess the performance of commercial methods for protein S (PS) antigen measurement. Twenty-five different samples were distributed deep-frozen (24 plasmas) or lyophilized (one plasma) to five laboratories. They were analyzed blind in each laboratory by the method used locally and by three commercial methods which included two electroimmunoassays (EIA), Asseraplate-PS (Diagnostica Stago), Rellplate-S (American Diagnostica) and an ELISA system, Asserachrom-PS (Diagnostica Stago). 1. Reproducibility. Average between-laboratory coefficients of variation were 15.4%, 17.6% and 25.3% for Asserachrom-PS, Asseraplate-PS and Rellplate-S. 2. Specificity. Results of all methods showed that PS is underestimated when C4b binding protein is high. This influence was particularly evident for the ELISA Asserachrom-PS and disappeared when the antibody-antigen incubation period was prolonged to overnight. 3. Sensitivity. In all laboratories ELISA detected even the lowest PS concentration (4 U/dl), whereas the two EIAs were less sensitive (lower detection limit 14 U/dl). All methods and laboratories correctly diagnosed a plasma sample from a PS congenitally deficient patient. Conclusions. This study shows that better standardization of PS immunoassays is necessary to improve accuracy and reduce interlaboratory variability before a candidate plasma standard can be successfully calibrated in an international collaborative study. PMID- 1412160 TI - Standardisation of factor VIII--V. Calibration of the 2nd International Standard for Factor VIII and von Willebrand factor activities in plasma. AB - The proposed 2nd International Standard for Factor VIII and von Willebrand Factor activities in plasma, NIBSC code 87/718, was assayed against the 1st IRP, 80/511, and against fresh normal plasma, in 21 laboratories. There were no significant differences between the various assay methods for factor VIII antigen, von Willebrand factor antigen, and von Willebrand factor ristocetin co-factor activity. For factor VIII clotting activity there was a significant difference between the results of one-stage and two-stage assays. Plasma 87/718 has now been established by the WHO Expert Committee on Biological Standardisation as the 2nd IS for factor VIII and vWF in plasma with the following potencies: VIII:C 0.60 IU/ampoule; VIII:Ag 0.91 IU/ampoule; vWF:Ag 0.91 IU/ampoule; vWF/RCo 0.84 IU/ampoule. PMID- 1412161 TI - Relationship between total prothrombin, native prothrombin and the International Normalized Ratio (INR). AB - Plasma levels of total prothrombin and fully-carboxylated (native) prothrombin were compared with results of prothrombin time (PT) assays for patients undergoing oral anticoagulant therapy. Mean concentrations of total and native prothrombin in non-anticoagulated patients were 119 +/- 13 micrograms/ml and 118 +/- 22 micrograms/ml, respectively. In anticoagulated patients, INR values ranged as high as 9, and levels of total prothrombin and native prothrombin decreased with increasing INR to minimum values of 40 micrograms/ml and 5 micrograms/ml, respectively. Des-carboxy-prothrombin increased with INR, to a maximum of 60 micrograms/ml. The strongest correlation was observed between native prothrombin and the reciprocal of the INR (1/INR) (r = 0.89, slope = 122 micrograms/ml, n = 200). These results indicated that native prothrombin varied over a wider range and was more closely related to INR values than either total or des-carboxy prothrombin. Levels of native prothrombin were decreased 2-fold from normal levels at INR = 2, indicating that the native prothrombin antigen assay may be a sensitive method for monitoring low-dose oral anticoagulant therapy. The inverse relationship between concentration of native prothrombin and INR may help in identification of appropriate therapeutic ranges for oral anticoagulant therapy. PMID- 1412162 TI - Vampire bat salivary plasminogen activator promotes robust lysis of plasma clots in a plasma milieu without causing fluid phase plasminogen activation. AB - Vampire bat salivary plasminogen activator (BatPA), human tissue-type plasminogen activator (tPA) or streptokinase (SK) were incubated in human citrated plasma containing a plasma clot that was radiolabelled with iodine-125 fibrin(ogen). Complete clot dissolution by BatPA (30 nM) was associated with slight activation of "fluid phase" plasminogen; the plasma levels of functional fibrinogen and alpha 2-antiplasmin decreased by only 8 and 19%, respectively. Addition of SK (3,600 IU/ml) to the clot-containing plasma caused complete clot lysis and massive activation of the "fluid phase" plasminogen, leading to greater than 60 and 96% decreases of the functional levels of fibrinogen and alpha 2-antiplasmin, respectively. Incubation of tPA (30 nM) in clot-containing plasma caused complete clot lysis as well as substantial activation of "fluid phase" plasminogen; the plasma levels of functional fibrinogen and alpha 2-antiplasmin decreased by 45 and 79%, respectively. The profound degradation of fibrinogen in the SK and tPA but not BatPA-containing samples was confirmed by immunoblot analysis. Additional experiments showed that the presence of soluble clot lysate in plasma containing tPA enhanced the extent of fibrinogen degradation from 25% to greater than 60%; the addition of soluble clot lysate to the plasma containing BatPA did not prompt further fibrinogen degradation. Finally, studies using exogenous alpha 2 antiplasmin suggested that plasmin generated via tPA-mediated activation of "fluid phase" plasminogen does not play an important role in clot dissolution. PMID- 1412164 TI - Depression of tissue-type plasminogen activator and enhancement of urokinase-type plasminogen activator as an expression of local inflammation. AB - Inflammatory processes are accompanied by extravascular deposition and breakdown of fibrin. We measured fibrinolytic parameters in synovial fluid (SF) and in plasma of 36 patients with rheumatoid arthritis (RA). As a control, SF of 13 patients with blunt knee trauma, and plasma of 17 healthy volunteers were studied. In RA patients, extravascular t-PA mediated plasminogen activation was depressed: mean SF tissue-type plasminogen activator (t-PA:Ag) concentration (2.1 +/- 1.6 ng/ml) was four-fold lower, and plasminogen activator inhibitor (PAI) activity (284 +/- 212%) four-fold higher than the plasma values of the same patients or of healthy donors. In contrast, u-PA related plasminogen activation was strongly enhanced: urokinase-type plasminogen activator (u-PA) antigen (23.1 +/- 12.4 ng/ml) was more than four-fold higher, single-chain u-PA (scu-PA) (5.3 +/- 1.9 ng/ml) three-fold higher than in plasma of the same patients or of healthy donors, and active two-chain u-PA (tcu-PA) was detected in 14 of the 36 SF samples of RA patients. All of these changes in extravascular fibrinolytic parameters correspond with those induced by inflammatory mediators in cell cultures. In joint effusions of patients with a blunt knee trauma, the effects were intermediate: u-PA related parameters showed moderate changes in the same direction as in arthritis; t-PA antigen was also decreased. The only exception was that PAI was not increased. We conclude that the findings in traumatic effusions reflect transient effects as a reaction to trauma. In joint inflammation, the depressed t-PA mediated plasminogen activation, although more than compensated by the enhanced u-PA mediated plasminogen activation, results in protraction of fibrin removal. Besides, the enhanced u-PA activation might lead to proteolytic damage of the cartilage. PMID- 1412163 TI - Thrombolytic and pharmacokinetic properties of a recombinant chimeric plasminogen activator consisting of a fibrin fragment D-dimer specific humanized monoclonal antibody and a truncated single-chain urokinase. AB - A recombinant chimeric plasminogen activator consisting of a humanized monoclonal antibody specific for cross-linked human fibrin (MA-15C5Hu) and a 32 kDa single chain urokinase-type plasminogen activator (scu-PA-32k) comprising amino acids Leu144-Leu411, MA-15C5Hu/scu-PA-32k, was previously found to have a 12-fold higher fibrinolytic potency than recombinant scu-PA-32k towards a human plasma clot in a human plasma milieu in vitro (Vandamme et al., Eur J Biochem 1992; 205: 139-46). Therefore, the thrombolytic and pharmacokinetic properties of MA 15C5Hu/scu-PA-32k were compared with those of recombinant single-chain urokinase type plasminogen activator (scu-PA) in 3 different venous thrombosis models in vivo. In hamsters with a pulmonary embolus consisting of a human plasma clot, the thrombolytic potency (% lysis per dose in mg/kg administered) of MA-15C5Hu/scu-PA 32k was 23-fold higher than that of scu-PA (p less than 0.0005). In rabbits with a jugular vein clot prepared from human plasma, the thrombolytic potency of MA 15C5Hu/scu-PA-32k was 11-fold higher than that of scu-PA (p = 0.012). In baboons with an autologous whole blood clot in the femoral vein, the chimera had a 5-fold higher thrombolytic potency than scu-PA. In all three animal species, the clearance of the chimera was 10- to 27-fold reduced as compared to scu-PA. The specific thrombolytic activity (% lysis per micrograms/ml steady-state plasma u PA antigen) was increased up to 7-fold with MA-15C5Hu/scu-PA-32k as compared with scu-PA, which is indicative of targeting of the chimera to the clot. No fibrinogen breakdown or alpha 2-antiplasmin depletion was observed during thrombolysis with the chimera. Thus, MA-15C5Hu/scu-PA-32k constitutes a recombinant chimeric plasminogen activator with a significantly enhanced thrombolytic potency in 3 different animal models of venous thrombosis. PMID- 1412165 TI - Lysine-binding heterogeneity of Lp(a): consequences for fibrin binding and inhibition of plasminogen activation. AB - Lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for atherosclerosis. Lp(a) consists of a LDL-like moiety with an additional glycoprotein, apo(a), linked to apolipoprotein B-100. Apo(a) has a high homology with plasminogen (Pg). In vivo, Pg is activated on a fibrin surface by tissue Pg activator (tPA). We prepared Lp(a) from plasma by sequential ultracentrifugation followed by lysine-sepharose affinity chromatography. We found that a changing (donor dependent) fraction of the Lp(a) did not bind to lysine-sepharose. This fraction, designated Lp(a)lys-, was further purified using gel filtration. Bound Lp(a) [Lp(a)lys+] was eluted with 0.2 M EACA. Apo(a) isoforms in both fractions were identical. In contrast Lp(a)lys+ inhibited Pg activation by tPA in vitro (IC50% 20 mg/l), whereas Lp(a)lys- did not. In addition Lp(a)lys- did not bind to CNBr-digested fibrinogen whereas Lp(a)lys+ did (Kd, app = 0.2 nM). Therefore we conclude that a changing donor dependent fraction of human plasma Lp(a) does not inhibit Pg activation in vitro and does not bind to CNBr-digested fibrinogen. PMID- 1412166 TI - Unexpected effects of aurin tricarboxylic acid on human platelets. AB - Aurin tricarboxylic acid (ATA) is a potent inhibitor of ristocetin-mediated platelet agglutination and of shear-induced, von Willebrand factor (vWf)-mediated platelet aggregation, probably via inhibition of vWf interaction with glycoprotein Ib (GPIb). We examined the effects of ATA (both the sodium salt and a solution of ATA in ethanol) on platelet functions in citrated plasma (PRP) and in suspensions of washed platelets in Tyrode-albumin solution (contains 2 mM Ca2+). ATA (42-211 micrograms/ml) blocked aggregation and release of granule contents induced by thrombin (0.15 U/ml in PRP; 0.03 U/ml in platelet suspension). Responses to higher concentrations of thrombin were not inhibited. ATA also prolonged thrombin-induced clotting of fibrinogen. Since ATA had no effect on fibrinogen-induced responses of chymotrypsin-treated platelets, ATA probably acts on thrombin rather than on fibrinogen. In PRP and platelet suspensions, ATA (acid form 106 micrograms/ml; sodium salt 122 micrograms/ml) had little effect on ADP-induced platelet aggregation. The sodium salt of ATA (61-122 micrograms/ml) enhanced collagen-induced aggregation and release by platelets in citrated plasma and by washed platelets; the enhancement was extensively inhibited by aspirin. With platelet suspensions, ATA significantly enhanced aggregation and release caused by low concentrations of sodium arachidonate (15 50 microM); aggregation and release caused by higher concentrations of arachidonate were somewhat inhibited by ATA. Arachidonate-induced aggregation and release were also enhanced by ATA in PRP. ATA enhanced aggregation and release induced by the calcium ionophore A23187; aspirin had little effect on the enhancement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412167 TI - Transient expression of recombinant glycoprotein Ib alpha polypeptides in COS cells that inhibit von Willebrand factor binding to the platelet glycoprotein Ib/IX complex. AB - The cDNA encoding the glycoprotein Ib alpha polypeptide has been expressed in COS cells. Transfection with full-length cDNA and a cDNA truncated at an internal XbaI site produced a recombinant polypeptide doublet with estimated molecular weights of 48 and 46 kDa (rGpIb alpha L318) which could be resolved into a single band of molecular weight 36 kDa following digestion with endoglycosidase F. A portion of the truncated polypeptide was retained in the endoplasmic reticulum of COS cells and slowly released. A second fraction was rapidly secreted into COS cell-conditioned medium and could be used for functional studies. Soluble rGpIb alpha L318 harvested from COS cell-conditioned medium inhibited ristocetin dependent binding of [125I]-vWF to fixed washed human platelets (IC50 20 nM). Binding was inhibited by reduction and alkylation of "rGp1b alpha L318" suggesting the need for a critical disulfide bond to maintain biological activity of the recombinant polypeptide. We conclude that the recombinant polypeptides produced by transfection of GpIb alpha cDNA into heterologous cells are secreted, soluble, and can inhibit vWF binding to platelet GpIb/IX. PMID- 1412168 TI - Defect of platelet aggregation and adhesion induced by autoantibodies against platelet glycoprotein IIIa. AB - A young patient developed chronic idiopathic thrombocytopenic purpura. Prednisone therapy normalized platelet number, but bleeding symptoms did not disappear. Platelet function was severely impaired, since platelet aggregation, ATP release and adhesion to collagen and subendothelial matrix were significantly reduced. Plasma and purified immunoglobulins of the patient reproduced the functional defects in normal platelets. Immunoblotting revealed that patient's plasma contained an antibody reacting with a component of platelets with the same electrophoretic mobility of glycoproteins IIIa of normal platelets. Moreover, patient's plasma inhibited the binding of an anti-GPIIb/IIIa monoclonal antibody to platelet surface. Additional immunosuppressive therapy with prednisone and azathioprine normalized platelet function and induced the disappearance of bleeding symptoms. PMID- 1412169 TI - Ridogrel inhibits systemic and renal formation of thromboxane A2 and antagonizes platelet thromboxane A2/prostaglandin endoperoxide receptors upon chronic administration to man. AB - The effects of ridogrel, a dual thromboxane A2 (TXA2) synthase inhibitor and TXA2/prostaglandin (PG) endoperoxide receptor antagonist, on systemic and renal production of prostaglandins and on platelet TXA2/PG endoperoxide receptors was evaluated upon chronic administration (300 mg b.i.d. orally, for 8 and 29 days) to man. Such a medication with ridogrel inhibits the systemic as well as the renal production of TXA2 as measured by the urinary excretion of 2,3-dinor-TXB2 and TXB2 respectively without inducing significant changes in systemic or renal PGI2 production. Simultaneously with the latter effects, the production of TXB2 by spontaneously coagulated whole blood ex vivo is inhibited (greater than 99%) while that of PGE2 and PGF2 alpha is largely increased. Administration of ridogrel causes a three- to five-fold shift to the right of concentration response curves for U46619 in eliciting platelet aggregation; no tachyphylaxis is observed after 29 days of treatment in this respect. Apart from a reduction of serum uric acid levels with a concomitant increase in urinary uric acid excretion during the first days of treatment, no clinically significant changes in hematological, biochemical, hemodynamic and coagulation parameters occur during the 8 days or 29 days study. The study demonstrates that ridogrel is a potent inhibitor of the systemic as well as renal TXA2 synthase and an antagonist of platelet TXA2/PG endoperoxide receptor in man, covering full activity during 24 h at steady-state plasma level conditions without tachyphylaxis during 29 days of medication. The compound is well tolerated, at least during 1 month of administration. PMID- 1412171 TI - Intravenous acetylsalicylic acid--dose-related effects on platelet function and fibrinolysis in healthy males. AB - Low-dose acetylsalicylic acid (ASA) has been shown to be beneficial in patients with acute myocardial infarction and unstable angina pectoris. Oral administration of ASA is difficult in the acute phase of these syndromes. In this study we evaluated the effect of 25 mg, 50 mg or 100 mg of ASA given as an intravenous bolus injection on platelet function and fibrinolysis in healthy males and related this to plasma concentrations of ASA. No adverse effects were found. A complete inhibition of serum thromboxane B2 synthesis was demonstrated 5 min after injection of 100 mg ASA intravenously. ASA disappeared from the circulation within 60 min after bolus injection and at this time thromboxane B2 synthesis was inhibited dose-dependently by 71%, 90% and 100% for doses of 25 mg, 50 mg and 100 mg, respectively. Inhibition of thromboxane B2 synthesis after 100 mg of intravenous ASA was still 96.5% at 24 h and 93.4% at 48 h after the injection. The bleeding time measured at 30 min after ASA administration was significantly prolonged on the average by 70 s, 144 s and 211 s after 25 mg, 50 mg and 100 mg of ASA, respectively. Minor, but significant changes were found in tissue plasminogen activator antigen and in plasminogen activator inhibitor within the first hour after injection of low dose ASA, but similar changes were found after injection of saline. No change in tissue plasminogen activator activity was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412170 TI - Studies of fibrinogen binding to platelets by flow cytometry: an improved method for studies of platelet activation. AB - Platelet function is dependent upon membrane receptors and their interaction with other proteins. Platelet activation appears to cause a structural change of the glycoprotein IIb/IIIa complex that exposes the fibrinogen binding site, which subsequently binds fibrinogen. Fluorescence-activated flow cytometry (FACS) is an efficient method for studying membrane proteins. Flow cytometry gives single-cell data, allowing the detection of only a small proportion of labelled platelets in whole blood without any washing steps. One problem with this method is that the labelled antibodies and the antigen, if present in plasma, form an immune complex, which may cause false positive reactions due to interaction between mammalian IgG and Fc gamma receptors on the platelets. We show that immune complexes with chicken IgG do not activate human platelets. We have developed a method for measuring platelet-bound fibrinogen in whole blood and platelet-rich plasma utilising fluorescein isothiocyanate (FITC)-conjugated chicken antibodies directed towards human fibrinogen. As low as 1% activated platelets could be detected without interference from Fc-interactions. PMID- 1412172 TI - Lack of correction of acquired heparin cofactor II deficiency in patients with liver failure after successful orthotopic liver transplantation. PMID- 1412173 TI - Reversible prothrombin time prolongation after plasma storage on dry ice. PMID- 1412174 TI - Danazol therapy in hypoplasminogenemia. PMID- 1412175 TI - A raised beta 2-glycoprotein I level does not prolong the DRVVT. PMID- 1412176 TI - Contributions of Mayme Williams to the elucidation of the multiple functions of plasma kininogens. PMID- 1412177 TI - Alfred L. Copley, the teacher and founder. PMID- 1412178 TI - The bioluminescent detection of platelet released ATP: collagen-induced release and potential errors. AB - The bioluminescent detection of ATP released from activated platelets is an important diagnostic and experimental assay. Potential errors in the interpretation of the data may be introduced due to the lability of luciferin luciferase and the amount of platelet agonist employed. Loss of luciferin luciferase activity is temperature dependent with a 50% decrease in activity in 1 4 min at 37 degrees C. Plasma components do not appear to contribute to the inactivation of the detection system. Due to the significant loss of enzyme activity at variable times, the method of standardizing ATP concentrations is crucial for the accurate determination of ATP released from activated platelets. A nearly 5-fold error is introduced into the routinely employed assay procedure where the standard ATP concentration is determined 5 min after the addition of agonist. This report demonstrates that the standard ATP concentration must be determined with a separate platelet sample at the same time as the ATP was released from the agonist-induced experimental platelet sample. A second significant error in the assay system may be introduced by the agonist concentration employed even when the final level of aggregation is the same. When collagen is employed as the agonist the amount of ATP released appears to depend, in part, on the initial intensity of the aggregation response and not on collagen type (Type I versus IV). The corrective procedures described here for the detection of ATP are not likely to change the qualitative results of most studies but would significantly alter the quantitative results. PMID- 1412179 TI - Role of platelet-activating factor in the development of endothelial dysfunction in hemorrhagic hypotension and retransfusion. AB - Platelet-activating factor (PAF), an important mediator of ischemic and shock states, has been shown to prime direct and neutrophil-mediated endothelial cell injury. In the present study we investigated therefore whether PAF is involved in the development of dysfunction of the cerebrovascular endothelium in hemorrhagic hypotension and retransfusion in cats. In vitro responses of middle cerebral arteries prepared from control animals and from animals subjected to hemorrhagic hypotension with or without specific PAF antagonist WEB 2086 treatment (1 mg/kg initial bolus followed by a 0.05 mg/kg/min infusion) were studied by measuring isometric force in organ chambers containing Krebs-Henseleit solution (37 degrees C, gassed with 95% O2-5% CO2). Bleeding was performed in a stepwise fashion by bringing the mean arterial blood pressure to 90, 70 and 50 mmHg and maintained for 20 min at each level followed by a 20-min retransfusion. Hemorrhagic hypotension and retransfusion caused a marked attenuation of the acetylcholine- and ATP-induced endothelium-dependent relaxations of the middle cerebral artery whereas the dilations induced by the nitric oxide donor and direct vasorelaxant SIN-1, remained unaltered. In the vessels, prepared from animals which received WEB 2086 treatment during hemorrhage and retransfusion there were more pronounced cholinergic (but not purinergic) relaxations than in the untreated animals subjected to hemorrhage. SIN-1 induced relaxations remained unaltered after WEB 2086 treatment. Our results suggest that platelet-activating factor is in part involved in the pathophysiological processes leading to the development of the endothelial dysfunction in the present model of hemorrhagic hypotension and retransfusion. PMID- 1412180 TI - Alfred L. Copley--the scientist and his contributions to our understanding of haemostasis, thrombosis and atherogenesis. PMID- 1412181 TI - Determination of r DNA hirudin and A-human thrombin- hirudin complex in plasma samples: enzyme linked immunosorbent assays for hirudin and complex vs. chromogenic thrombin substrate assay. AB - rDNA hirudin plasma concentrations in man and rhesus monkeys were determined over a period of 15 and 24 h. The plasma concentration of alpha-human thrombin-hirudin complex was measured after administration of the complex to rhesus monkeys. The complex was also determined after administration of hirudin to man and rhesus monkeys to study a possible formation of a complex with alpha-human thrombin in blood. The determination of hirudin was performed by a sandwich ELISA, using polyclonal and monoclonal antibodies and the chromogenic thrombin substrate assay. The alpha-human thrombin-hirudin complex concentration in the plasma of rhesus monkeys was measured over a period of 48 hours. The results of a sandwich ELISA were compared with those of the chromogenic thrombin substrate assay. A good agreement between the total hirudin concentrations analyzed by the hirudin ELISA and the alpha-human thrombin-hirudin complex ELISA and those of the chromogenic thrombin substrate assay, measuring total hirudin, too, was observed. PMID- 1412182 TI - Preparation of plasma for the detection of lupus anticoagulants and antiphospholipid antibodies. AB - The effect of different methods of plasma preparation on the results of 1) a clotting assay for lupus anticoagulant (LA) detection (the dilute activated partial thromboplastin time, dAPTT), and of 2) an ELISA test for anticephalin antibody (aCEPHA) detection, was evaluated. It is well known that platelet disintegration resulting from freeze-thawing of plasma samples may release procoagulant phospholipid--"LA-bypassing" activity. Even with fresh plasma, the dAPTT of LA positive samples was sensitive to the presence of residual blood platelets. This effect was accentuated by freezing and thawing: with test plasma that had been prepared by a centrifugation force of 3,000 g or less for 15 min at 4 degrees C, freeze-thawing caused a significant shortening of the dAPTT. This phenomenon could not be demonstrated with filtered test plasma, which was platelet free. Surprisingly, ultracentrifugation also led to a substantial shortening of the dAPTT compared to filtered plasma, and should not be recommended as a method of plasma preparation for LA detection. The ELISA test was less sensitive to residual platelets than the dAPTT. Thus, plasma prepared by a centrifugation force of at least 1,500 g may be stored at -20 degrees C before performance of the ELISA test. For the dAPTT, filtering of test plasma and control plasma after centrifugation is recommended for maximum sensitivity, regardless of whether they are to be examined in the fresh state or after freezing and thawing. PMID- 1412183 TI - Effects of long-term treatment with warfarin on fibrinogen, FPA, TAT, and D-dimer in patients with coronary artery disease. AB - Sixty-four patients undergoing aorto-coronary bypass surgery were randomized to receive antithrombotic treatment with acetylsalicylic acid (ASA), 300 mg/d (n = 30) or warfarin, INR = 2.5 - 4.2 (n = 34). The levels of fibrinogen, thrombin antithrombin III complexes (TAT), fibrinopeptide A (FPA) and D-dimer were assessed before surgery and 9 months postoperatively. In the warfarin treated group the fibrinogen levels were increased after 9 months, while the levels of TAT, FPA and D-dimer were decreased. In the ASA group TAT levels were increased at 9 months, whereas no significant changes in fibrinogen, FPA or D-dimer from baseline were noted. Thus, a reduced activation of the coagulation system has been demonstrated during long-term treatment with warfarin in patients with coronary artery disease. PMID- 1412184 TI - HA-29: an inhibitor of thromboxane A2 formation with antagonism of thromboxane A2/prostaglandin endoperoxide receptor in rabbit platelets. AB - HA-29, 2-[(3-methoxyphenyl)methyl]-pyrano[2,3-c]pyrazol-6(1H)-one, was investigated for its inhibitory mechanism of action in washed rabbit platelets. This compound inhibited the aggregation and ATP release of rabbit platelets induced by arachidonic acid and collagen in a concentration-dependent manner, without affecting those induced by ADP, PAF and thrombin. Prolongation of the incubation time of HA-29 with platelets did not cause further inhibition and the aggregability of the agent-treated platelets could be restored after washing of platelets. The concentration-response curve of U-46619-induced platelet aggregation was shifted to the right by HA-29 in a concentration-dependent manner, but the maximal aggregation was suppressed by HA-29. The pA2 and pA10 values of HA-29 on U-46619-induced platelet aggregation were 4.26 and 3.58, respectively, with a slope value of -1.4. The U-46619-induced aggregation was markedly disaggregated by HA-29 even it was added 5 min after U-46619. HA-29 inhibited the secondary aggregation and ATP release, but not the primary aggregation of human platelet-rich plasma induced by ADP and epinephrine. Thromboxane B2 formation caused by arachidonic acid, collagen and thrombin was markedly suppressed by HA-29. HA-29 also inhibited the formation of prostaglandin D2 caused by arachidonic acid. HA-29 inhibited almost completely the formation of inositol monophosphate caused by U-46619, but not that by collagen or thrombin. HA-29 did not affect U-46619-induced contraction of rat aorta. It is concluded that the antiplatelet effect of HA-29 is due to the inhibition of thromboxane A2 formation and blockade of thromboxane A2/prostaglandin endoperoxide receptor. PMID- 1412185 TI - Enhancement of t-PA release by mucopolysaccharide polysulphate. PMID- 1412186 TI - Three missense mutations in Arg codons of the factor VIII genes of mild to moderately severe hemophilia A patients. PMID- 1412187 TI - Low concentrations of sodium azide specifically inhibit a thromboxane A2 pathway in human platelets. AB - Sodium azide completely inhibits the serotonin release induced by ADP, arachidonic acid and the thromboxane A2 mimetic U46619, but does not have any effect on the activation by PMA. Collagen and thrombin are inhibited when used at low concentrations, but not at high concentration. This pattern of activation suggests that the inhibition by azide is not a metabolic inhibition. The antagonism of U46619-induced secretion was further studied and was shown to be non-competitive. It is selective for certain components of the U46619 stimulus response coupling: aggregation, serotonin secretion and the activation of protein kinase C are completely or almost completely inhibited by 300 microM sodium azide. Shape change, calcium elevation, cytoplasmic alkalinization and phosphorylation of myosin light chain are only partially modified. This suggests that azide may specifically inhibit one of the different forms of thromboxane A2 receptors present in platelets. PMID- 1412188 TI - Influence of heparin treatment on biochemical markers of an activation of the coagulation system. AB - Monitoring of anticoagulant treatment is not yet satisfactory. Otherwise optimal treatment control in special situations as low dose heparin prophylaxis in hip surgery or high dose anticoagulant treatment in patients after coronary stent implantation may be desirable. Recently available thrombin markers were analyzed in 51 patients under low dose (group 1) and 30 patients under high dose therapy with unfractionated heparin (group 2a and b) as well as in controls (n = 26). Before therapy these parameters were significantly elevated in both patient groups. Elevated thrombin-antithrombin III-complexes (TAT) despite adequate prolongation of aPTT under high dose heparin in 38.2% of patients indicate that therapeutic concentrations of heparin in these cases are insufficient for depressing this parameter completely. During low dose therapy only prothrombin fragment (F1 + 2) significantly decreased. This may be explained by catalytic induction of TAT-complex formation by heparin. Decrease of D-Dimer under heparin therapy in both groups does not parallel with TAT and F1 + 2 but was more prolonged. This can be explained by dependence of the D-Dimer level on spontaneous fibrinolytic activity and by a longer plasma half-life as well as a chronic and continuous fibrinolytic process in an older thrombus. In conclusion, thrombin markers seem to be helpful in estimating anticoagulant treatment efficacy. As a consequence, anticoagulant treatment has to be intensified in high risk patients for complete depression of these markers. Whether the benefit of higher heparin doses is worth the risk of drug-induced hemorrhage, however, remains to be clarified in clinical studies. PMID- 1412189 TI - Effect of physical stress on 5-hydroxytryptamine uptake kinetics (Km and Vmax) in human platelets. AB - Platelet 5-HT uptake is possibly one mechanism by which plasma level of 5-HT is physiologically controlled. This mechanism may be of importance in the vascular 5 HT mediated tone and protect against thrombolysis and cardiovascular events. Physical stress is known to affect various platelet functions. The aim of this study was to investigate whether or not physical stress has any influence on platelet 5-HT uptake kinetics. In healthy adult persons (n = 13) the maximal rate (Vmax) and Michaelis-Menten constant (Km) of platelet 5-HT uptake (in vitro) were determined before (a), immediately after (b) and 1 hour after 50 min of squash playing (c). Immediately after squash Vmax and Km were elevates significantly as compared to the values before squash [Vmax(a): 77.0 +/- 31.0 (SD) pmol 5-HT/10(8) pl./min, Vmax(b): 109.9 +/- 48.4 (SD) pmol 5-HT/10(8) pl./min, p less than 0.01; Km(a): 5.16 +/- 1.73 (SD) x 10(-7) mol/1, Km(b): 7.59 +/- 2.37 (SD) x 10(-7) mol/1, p less than 0.05]. The percent elevations of Vmax (47%) and Km (42%) were of the same range. One hour after squash the values of Vmax(c) and Km(c) were found to be normalized. It is concluded that physical stress, like squash playing, does not affect net platelet 5-HT uptake in healthy persons at physiological plasma 5-HT concentrations. The significant increases of Vmax and Km of platelet 5-HT uptake are suggested to be adaptation reactions to keep the platelet net 5-HT uptake constant. PMID- 1412190 TI - Activation of human prothrombin by the venom of Lonomia achelous (Cramer) caterpillars. AB - In this paper, we demonstrated that the procoagulant action of Lonomia achelous (Cramer) is due in part to a component that activates prothrombin. The activation by crude venom and Fractions obtained by gel filtration on Sephadex G-75 is not dependent of phospholipid, Ca++ or Factor V. The activation of prothrombin by Fraction I is greatly stimulated by Factor V in the presence of phospholipid and Ca++; in presence of SBTI, we found that the Fraction I and Factor Xa act in a similar manner. These results suggest that the Fraction I is a Factor Xa - like prothrombin activator. PMID- 1412191 TI - Rapid quantitative evaluation of plasma D-dimer levels in thrombotic states using an automated latex photometric immunoassay. AB - To evaluate a recently developed latex photometric immunoassay (LPIA) that which can measure 40 samples quantitatively within 30 minutes, we measured D-dimer levels in blood samples obtained from patients with disseminated intravascular coagulation (DIC). Linearity of D-dimer determination was shown over the range from 0.5 to 36 micrograms/ml, and recovery studies demonstrated 94 to 108% recovery. The intra-assay and inter-assay coefficients of variation ranged from 0.6 to 11.3% at plasma D-dimer levels of 0.54 to 30.1 micrograms/ml. No interference by lipids, bilirubin, haemoglobin, rheumatoid factor, or gamma globulin was noted. The normal D-dimer range was less than 0.5 microgram/ml in healthy ambulatory subjects, while the level in elderly subjects with atherosclerosis (14%) or in immobilized subjects (38%) was well above this limit. There was a strong correlation between plasma and serum D-dimer levels (r = 0.993). D-dimer levels measured by this LPIA showed a good correlation with those determined using two kinds of ELISA. The LPIA D-dimer levels were elevated in some subjects with diseases predisposing to DIC, but remained below 10.0 micrograms/ml. On the other hand, the LPIA D-dimer levels in DIC subjects were almost always above 10.0 microgramS/ml. Our study showed that a hypercoagulable state should be suspected when the LPIA D-dimer level is greater than 0.5 microgram/ml and that DIC should be diagnosed when the level is greater than 10.0 micrograms/ml in the presence of an appropriate underlying disease. This LPIA system can rapidly evaluate the presence of a hypercoagulable state as accurately as any ELISA, and thus seems potentially valuable for both emergency and routine laboratory use. PMID- 1412192 TI - A computerised system of screening for deep venous thrombosis. AB - We have developed a computer controlled system of strain gauge plethysmography for use as a screening tool for proximal segment venous thrombi which is simple to use, well tolerated by patients and extremely accurate. The computerised test was evaluated in 171 limbs of 163 symptomatic patients by comparison with subsequent ascending venography. Each of twenty occlusive proximal segment thrombi were identified, one non occlusive thrombus screened normal giving an overall sensitivity of 95.2%. The specificity of the test was 80% with a negative predictive value of 99.0%. The computerised system allows accurate screening for proximal segment venous thrombosis, and may permit more selective use of venography in the symptomatic post-operative limb. PMID- 1412193 TI - Hemorheological alterations in mild essential hypertension. AB - Blood rheological properties were studied in 21 patients suffering from essential hypertension (EHT), degree I-II according to WHO criteria. These patients were diagnosed "de novo". The whole blood filterability (WBF), blood viscosity (BV) at 230 s-1 and 23 s-1, red cell deformability (FI), erythrocyte aggregation in autologous (MEA) and normal plasma (MEAc), fibrinogen (Fbg) and hematocrit (Ht) have been evaluated. In the hypertensive patients we have found decreased WBF, greater BV and FI in comparison with the control group (p less than 0.001). Likewise, MEA and Fbg were increased, though the differences were less significant (p less than 0.01). The evaluation of Ht did not show any differences between the two groups. The results suggest that in the newly diagnosed EHT, clear hemorheological alterations occur, both in plasma and in the erythrocytes, which could play a role in the pathogenesis of the aforementioned disease. PMID- 1412194 TI - Soluble, cross-linked fibrin(ogen) hybrid oligomers do not stimulate t-PA conversion of plasminogen. AB - Cross-linked hybrid oligomers of fibrinogen and fibrin are found in plasma from fibrinaemic patients and normal individuals as well as in preparations of purified human fibrinogen. The present study was undertaken to see if such hybrid oligomers have the same stimulatory effect on tissue plasminogen activator (t-PA) conversion of plasminogen as do polymeric and monomeric fibrin. Hybrid oligomeric fibrin(ogen) material was provided by subjecting purified human fibrinogen to gel filtration in urea-containing buffer at pH 5.6. Well separated fractions of hybrid oligomeric material and monomeric fibrinogen were thus obtained. Some of this material was converted to soluble polymeric or monomeric fibrin using insolubilized thrombin. Hybrid polymeric fibrin, polymeric fibrin or monomeric fibrin were then added to citrated, normal plasma to 2.5 or 5 per cent of the plasma fibrinogen concentration. The added material was kept in solution by plasma fibrinogen. The "COA-SET Fibrin Monomer Test" (Kabi,Stocholm,Sweden), based on the ability of fibrin monomers to enhance t-PA mediated plasminogen plasmin conversion, was used to compare the potential stimulatory effect of the preparations above. The results led to the following conclusions: 1) Cross linked, soluble fibrin(ogen) hybrid polymers in a concentration of 5 per cent of plasma fibrinogen concentration (w/w) do not stimulate t-PA. 2) Thrombin conversion of the fibrin-fibrinogen hybrid material resulted in an increase in the rate of t-PA mediated plasminogen conversion, corresponding to the one observed with equivalent (w/w) amounts of fibrin monomers. Compared on a mole to mole basis, fibrin oligomers are more powerful than fibrin monomers as stimulators of t-PA activity. PMID- 1412195 TI - Platelet microvesicles adhere to subendothelium and promote adhesion of platelets. AB - A role in hemostasis has been suggested for platelet membrane microvesicles (mv). The objectives of the studies reported here include functional analysis of platelet mv in models developed for study of platelet adhesion, as well as investigation of possible interactions between mv and intact platelets in these same adhesion models. Microvesicles were prepared from washed platelet concentrates by repeated freezing and thawing. Adhesion to subendothelium was measured quantitatively by radiolabelling mv with 111-In, and morphologically by scanning electron microscopy. Platelet mv adhered to subendothelium quantitatively over time. Using a modified Baumgartner chamber, we found adhesion of mv to subendothelium significantly increased with increasing shear rates. With this same model we found that prior exposure of subendothelium to mv greatly increased subsequent adhesion of platelets to the same everted vessel, compared to platelet adhesion in the absence of mv. All of these experiments were conducted with mv suspended in ACD/saline, indicating that plasma components are not essential for adhesion of mv. Our studies show that platelet mv adhere to subendothelium in much the same way as do platelets, and support the concept of a hemostatic role for mv in that they appear to increase platelet adhesion. PMID- 1412196 TI - Thromboxane does not play a significant role in acute, cold-induced vasoconstriction in Raynaud's phenomenon. Studies with combined thromboxane synthase inhibition and thromboxane receptor antagonism. PMID- 1412197 TI - Familial elevation of plasma histidine-rich glycoprotein. A case associated with recurrent venous thrombosis and high PAI-1 levels. PMID- 1412198 TI - Pharmacokinetic investigations of the alpha-human thrombin-hirudin complex in rhesus monkeys. PMID- 1412199 TI - Plasminogen activators and plasminogen activator inhibitor 1 before and after venous occlusion of the upper limb in thromboangiitis obliterans (Buerger's disease). AB - Plasma levels of plasminogen activators (t-PA, u-PA) and their inhibitor (PAI-1) were studied in patients suffering from Buerger's disease and healthy volunteers before and after 15 minutes of venous occlusion test. The baseline levels of t-PA in group of patients did not differ from those of controls. On the contrary patients with Burger's disease showed a marked increase in u-PA antigen concentrations with concomitant decrease in PAI-1 antigen levels. During venous stasis t-PA antigen concentrations increased in all subjects, however it was much pronounced in controls. Venous occlusion resulted in significant decrease in free PAI-1 levels in the group of patients only. In conclusion, Buerger's disease is associated with the endothelial derangement with increased u-PA release and decreased PAI-1 release, which does not influence the function of fibrinolytic system. The fact that the reduced response of the endothelium to release t-PA after venous stasis goes in parallel with marked decrease in PAI-1 antigen levels seems to suggest that patients suffering from Buerger's disease are not at high risk of intravascular fibrin deposition. PMID- 1412200 TI - Pharmacological profile of G619, a new platelet aggregation inhibitor. AB - G619, a 4-OH-isophthalic acid derivative, was studied for its capacity to inhibit platelet aggregation. G619 dose-dependently inhibited U46619, collagen, ADP, PAF, thrombin and epinephrine-induced platelet aggregation in vitro. The IC50 values for inhibition of U46619-induced human and rabbit platelet aggregation were 39 and 43 microM, respectively. G619, at 100 microM, inhibited high concentration collagen (10 micrograms/ml)-induced aggregation of rabbit platelets pretreated with indomethacin and increased the level of cAMP in washed rabbit platelets by 30% (p less than 0.01 vs basal). However, G619, did not inhibit fibrinogen binding to GPIIb/IIIa receptor, phosphodiesterase, U46619-induced contractile responses on canine saphenous vein or rabbit aorta, calcium-induced vasoconstriction and thrombin or PAF-induced elevation of [Ca++]i in platelets in vitro. In vivo, the U46619-induced maximal thrombocytopenia in rats was reduced from 40% (vehicle) to 22% and 18% by 10 and 30 mg/kg of G619 i.v., respectively. G619 (30 mg/kg) had no effect on the U46619-induced vasopressor response or sudden death in rats, and had no effect on TxB2 formation. Our results indicate that G619 is a broad-spectrum platelet aggregation inhibitor and may have its effect on a common mechanism for platelet aggregation besides an effect on the thromboxane A2 receptor. PMID- 1412201 TI - Laboratory heterogeneity of the lupus anticoagulant: a multicentre study using different clotting assays on a panel of 78 samples. Hemostasis Committee of the "Societe Francaise de Biologie Clinique". AB - The laboratory heterogeneity of the lupus anticoagulant (LA) was investigated in a multicentre study using a panel of 78 plasma samples diagnosed as containing a LA. Consecutive samples were collected by 12 participants using various screening tests, and sent to 7 laboratories which performed one or more clotting assays among the following: activated partial thromboplastin time (APTT), dilute Russell viper venom time, kaolin clotting time (KCT), dilute tissue thromboplastin time (dTTI) and a platelet neutralization test. For APTT and dTTI, 10 versions of these tests including standard and mixing procedures were carried out. They varied by reagents, phospholipid concentration or methodology. Cut-off times were determined for each test by comparing the results of the panel to those of a control population. When the data of all clotting assays were pooled, 70 of the 78 selected plasmas were considered to contain LA, 15 of them having a low-titer inhibitor. Sensitivity, defined as the proportion of positive results among LA containing plasmas, varied from 62 to 100% and was positively related to responsiveness (defined as the mean ratio of clotting time to cut-off time). Laboratory heterogeneity of LA-containing plasma was illustrated by a star symbol plot analysis. Different populations of samples, with LA preferentially recognized by one assay (or group of assays) irrespective of the overall sensitivity of this assay, were identified. Multiple component analysis demonstrated the heterogeneity of low-titer inhibitors, which complicates their recognition in routine laboratory investigation. PMID- 1412202 TI - Blood compatibility of venous prosthesis made of textile or non-textile material. AB - To study blood compatibility of venous prosthesis made of textile or non-textile material, the inferior vena cava of 37 rabbits was partly replaced by 3 mm internal diameter synthetic tube graft made of textile material (T: woven tetron) or non-textile material (P: polytetrafluoroethylene). At designated time intervals after the replacement (5 hours to 4 weeks), graft patency was examined and the dry weight of intraluminal deposits was measured. The harvested grafts were then subjected to light and scanning electron microscopy. All the T-grafts were occluded as early as 5 hours after grafting but when ticlopidine was administered prior to the grafting, all the grafts were patent. All the P-grafts were patent up to 4 weeks after grafting, though the amount of intraluminal deposits was increased in a time related manner, narrowing the lumen of the grafts. The luminal surface of the P-grafts harvested at 5 hours after grafting was covered by piles of fibrin networks entrapping erythrocytes without an association of platelet aggregates, which resembles the finding in the T-grafts harvested from the ticlopidine treated rabbits. In the P-grafts, both the proximal and distal luminal surfaces near the anastomosis were fully covered with endothelial cells by 2 weeks and the entire luminal surface was covered with these cells by 4 weeks. From these results, the following conclusions were obtained; (1) P-graft was superior to T-graft for venous prosthesis, which is mainly due to the inertness of P against platelet activation. (2) Though the luminal surface of the P-grafts was completely covered with endothelial cells by 4 weeks after grafting, the lumen was markedly narrowed by intimal hyperplasia. PMID- 1412203 TI - Increased levels of tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor (PAI) correlate with tumor necrosis factor alpha (TNF alpha) release in patients suffering from microangiopathy following allogeneic bone marrow transplantation (BMT). AB - Severe microangiopathy resembling thrombotic thrombocytopenic purpura (TTP) has been reported as a complication of acute graft-versus-host disease (aGvHD) in patients receiving cyclosporin (CsA) prophylaxis following allogeneic BMT. In order to analyze the pathophysiological events involved in microangiopathy, a prospective study comparing release of von Willebrand Factor (vWF), t-PA and PAI, as well as TNF alpha and further coagulation parameters was performed in 32 patients. Endothelial damage as the central lesion was confirmed by the close association of vWF and t-PA:Antigen with severity of microangiopathy. t-PA activity, however, was neutralized by a simultaneous rise in PAI. Activation of coagulation in the course of microangiopathy was further confirmed by increased levels of DDimer (DDi), fibrinopeptide A (FPA), beta-thromboglobulin (beta TG) and platelet factor 4 (PF4). As clinical grades of microangiopathy, as well as the release of t-PA:Ag and PAI were correlated with systemic release of TNF alpha our data further support our hypothesis of cytokine induced endothelial damage in clinical complications following allogeneic BMT. PMID- 1412204 TI - Subcellular localization of radioactively labelled defibrotide in cultured endothelial cells. AB - Defibrotide is a new antithrombotic and fibrinolytic drug which is obtained by controlled depolymerization of mammalian DNA. In various models of arterial and venous thrombosis, it has been shown that it induces tissue plasminogen activator [tPA] and prostacyclin [PGI2] release from the vessel wall. We have previously shown the presence of specific binding sites with a Kd of 4.2 micrograms/ml for radioactively labelled defibrotide. The present study was undertaken to identify the location of the binding site. Confluent cultures of endothelial cells from human umbilical vein were incubated with media containing 3H-acetyl-defibrotide for various intervals of time. Cells were then washed and harvested nonenzymatically. Subcellular location of 3H-defibrotide was investigated by fractionating cells on discontinuous sucrose gradient and measuring the distribution of radioactivity. 5'-nucleotidase enzyme activity was also measured to ensure the location of membrane fraction. Our results suggest that the major location of 3H-defibrotide in endothelial cells is the plasma membrane. On the other hand, nuclei also contain a considerable amount of the drug which suggests a mechanism where binding to a membrane protein is followed by internalization. PMID- 1412205 TI - Plasma fibrinolytic activity in healthy subjects with high and low lipoprotein(a) concentrations. PMID- 1412206 TI - Purification of factor XIa inhibitor from human platelets. AB - An inhibitor of activated factor XI (FXIa) in human platelets was recently identified as an amyloid beta-protein precursor (APP). We purified an FXIa inhibitor (XIaI) from the supernatant of activated human platelets, and assessed its inhibitor activity toward FXIa amidolytic activity. Approximately 90 micrograms of XIaI that cross-reacted with anti-APP antibody was obtained from two hundred units of platelet suspension by employing a six-step column chromatography procedure. The molecular weight of the purified XIaI was 94,000. The Ki value of XIaI to factor XIa was 526 +/- 120 pM, and the inhibition was enhanced by the addition of ZnCl2. The amino-terminal sequence of XIaI was L-E-V P-T-D-G-N-A-, which is identical to that for the leucine (N18) to alanine (N26) sequence of APP751 and the amino-terminal sequence of protease nexin-2. PMID- 1412207 TI - Formation of an association between factor XII and kallikrein in human plasma- significance of storage of plasma and the functional state of plasma kallikrein. AB - In a previous study evidence was provided that zymogen FXII might associate with part of the kallikrein generated by acetone treatment of human plasma in the presence of benzamidine (Thromb. Res. 61, 123-133, 1991). Some results also suggested an increase in such a complex formation upon storage of plasma, and two questions were raised in the present study: Does kallikrein activated by acetone treatment of plasma exist in modifications with different abilities to associate with FXII? And will -70 degrees storage of plasma increase the liability to complex formation? S-2302 amidase assays carried out in mixtures of normal plasma and plasma genetically deficient in prekallikrein (PK) suggested an inhomogeneity of the kallikrein generated. A minor and unstable part of it could be blocked by corn trypsin inhibitor, thus indicating the presence of an association with FXII. In fractions from gel filtration of acetone-activated plasma, kallikrein was assayed as S-2302 amidase, high molecular weight kininogen (HK) was measured in rocket immunoassay, and FXII, PK and HK were studied in PAGE immunoblot experiments. When freshly collected plasma was used, an amidase double peak (mol. wts. 400 and 300 kD) indicated an inhomogeneity of the kallikrein present, HK being observed in both peaks. FXII eluted separately over a gel. mol. wt. range of 90-55 kD. When plasma was stored at -70 degrees for 10 months before use, the more low-molecular part of the kallikrein double-peak had disappeared and was recovered, in a highly unstable state, adsorbed to the column material together with HK and FXII. Accordingly both functional assays and the results of immunoblot experiments indicated an inhomogeneity of the kallikrein present, and also a tendency of the minor part of it to associate with FXII, a tendency increased upon storage of plasma at -70 degrees. PMID- 1412209 TI - Fibrinolytic abnormalities. A Spanish multicenter study ebt.I on 443 patients with venous thromboembolic disease. PMID- 1412208 TI - Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyelocytic leukemia. AB - We measured plasma heparin cofactor II (HC II) activity in patients with disseminated intravascular coagulation (DIC) due to various underlying diseases together with the levels of antithrombin III (AT III), pseudocholinesterase (a marker of hepatic synthesis), and various haemostatic molecular markers. Both HC II and AT III were decreased in DIC secondary to all the underlying diseases studied, except acute promyelocytic leukemia (APL), when compared with healthy subjects. The lowest HC II and AT III levels was observed in coagulopathy secondary to liver disease, the HC II level in sepsis was the second lowest. In DIC due to APL, the decrease in HC II was not accompanied by a decrease in AT III. Thus, we divided all 124 samples tested into APL and non-APL groups. The HC II level correlated positively with fibrinogen and plasminogen in both the APL and non-APL groups. In the APL group, the HC II level had a significant negative correlation with the thrombin-AT III complex (TAT), fibrinogen/fibrin degradation products, and D-dimer levels as well as the prothrombin time, while AT III showed no correlations with any of the haemostatic parameters. These results suggest that HC II may be consumed preferentially by thrombin in APL patients with DIC, and thus may spare the consumption of AT III. Accordingly, HC II seems to be a superior indicator of DIC than AT III in APL patients. Moreover, replacement therapy with HC II instead of AT III may be useful to treat DIC associated with APL. In the non-APL group, the HC II levels were positively correlated with the levels of AT III and pseudocholinesterase activity. This indicates that plasma HC II levels are closely related not only to consumption coagulopathy but also to hepatic synthetic activity, as is the case for plasma AT III. PMID- 1412210 TI - Antibodies to anionic phospholipids in normal human, rabbit and mouse sera. PMID- 1412211 TI - Helge Stormorken--still going strong at 70. PMID- 1412212 TI - Portrait of a scientist. PMID- 1412213 TI - New methods may allow answers to old questions in vascular biology. PMID- 1412214 TI - Thoughts on future trends in studies of the thrombo-haemorrhagic balance. PMID- 1412215 TI - Gene transfer in the hemophilias: retrospect and prospect. PMID- 1412216 TI - The haemophiliac in the society. PMID- 1412217 TI - Purification of tissue factor pathway inhibitor (TFPI) from rabbit plasma and characterization of its differences from TFPI isolated from human plasma. AB - Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that is thought to function as a natural anticoagulant to regulate tissue factor induced coagulation (Proc. Natl. Acad. Sci. U.S.A. 88, 708, 1991). TFPI's mechanism of action has been well characterized as a two step reaction in which TFPI combines with factor Xa and subsequently TFPI/factor Xa combines with and effectively neutralizes factor VIIa/tissue factor. In human plasma, TFPI occurs in two major molecular weight forms of 34 and approximately 40 kDa. The 40 kDa form is a heterodimer of TFPI in covalent disulfide linkage to human apolipoprotein AII. TFPI circulates in human plasma primarily in association with the plasma lipoproteins. We have now isolated and partially characterized TFPI from rabbit plasma and find that, although functionally and immunologically related to TFPI isolated from human plasma, it differs from human TFPI in some of its physical properties. Rabbit TFPI is larger (approximately 45 kDa) and more extensively glycosylated than human TFPI, does not form mixed disulfides with other proteins in plasma, and unlike its human counterpart, does not circulate in plasma associated with lipoproteins. PMID- 1412218 TI - Changes in plasma tetranectin following hip surgery with or without thrombotic complications. AB - The fibrinolytic system seems to play a role in the development of postoperative thromboembolic complications (DVT). The newly described tetrameric protein tetranectin (TN), which has been found to enhance the activation of plasminogen to plasmin, therefore was studied in 55 patients who had total hip replacement and solely elastic stockings as physical thromboprophylaxis. No significant difference in plasma TN was found between the 5 patients with DVT and those without DVT, neither preoperatively or postoperatively at day 0, 1, 3, 7 or 10. A significant decrease in plasma TN was found from preoperative to postoperative values, indicating that TN may be a possible marker for other postoperative events. Because of the observed postoperative decrease it is important to consider the sampling time in the future research with TN. PMID- 1412219 TI - A method for quantitative determination of flow induced human platelet adhesion and aggregation. AB - Adhesivity and aggregability of blood platelets may reflect normal and diseased states. A quantitative assessment of such reactivity should thus provide further insight into disease mechanism. The well defined conditions of stagnation point flow using platelet-rich-plasma (PRP) as fluid permit quantitative treatment of the formation of platelet microthrombi on the stagnation plate. By measuring the growth kinetics (photometry) and corresponding morphology (light- and electron microscopy) of the microthrombus, platelet adhesion as well as aggregation could be analyzed separately by means of a quantitative procedure. Parameters are evaluated for PRP samples obtained from patients exhibiting deep venous thrombosis, arterial angiopathy or myocardial infarction, respectively. The results obtained demonstrate the usefulness of the proposed method for quantifying platelet reactivity as reflected by type and degree of flow induced platelet deposition. This, in turn, provides a basis for correlating the in vitro findings with the disease state. PMID- 1412221 TI - F1 + 2 and FpA in urine from patients with multiple trauma and healthy individuals. A pilot study. PMID- 1412220 TI - Affinity chromatography of platelets on immobilized thrombin: retention of catalytic activity by platelet-bound thrombin. AB - Radioactivity from I125-labeled human platelets was measured to estimate the extent of binding of platelet surface proteins to immobilized thrombin. 1-3% of the radioactivity was bound with 10-20% of this amount apparently irreversibly bound to the thrombin matrix. Site-specific chemical modification of thrombin with pyridoxal-5'-phosphate, N-bromosuccinimide or tetranitromethane resulted in a variable reduction of the amount of radiolabel bound. When thrombin modified with H-D-PheProArg-chloromethyl ketone (PPACK) was coupled to the matrix, there was no difference in the binding of platelet membrane proteins when compared to a control thrombin preparation while thrombin modified with tosyl-Lys-chloromethyl ketone (TLCK) coupled to the matrix did not bind radiolabel any more effectively than albumin which served as the control. However, when thrombin was modified with PPACK after coupling to the agarose matrix, ability to bind radiolabel was lost. Thrombin bound to platelets remained catalytically active when assayed with a peptide nitroanilide substrate. These results suggest tight binding between thrombin and platelets that is not only not dependent on active site integrity but leaves the bound thrombin catalytically competent. PMID- 1412222 TI - Arterial thrombosis model with photochemical reaction in guinea-pig and its property. AB - We have already developed an arterial thrombosis model in the rat femoral artery which utilized photochemical reaction between systemically injected rose bengal and transillumination of a green light with 540 nm wave length from the outside of the vessel. In the present study, we applied this model to guinea-pigs in order to produce a more suitable thrombus model for evaluation of antithrombotic drugs which act on the prostaglandin cascade. In the guinea-pigs, the irradiated femoral artery was completely occluded in 7 min after the injection of rose bengal (10 mg/kg) in a similar manner to the rats. The processes of primary endothelial injury and the subsequent formation of thrombus during this manipulation were observed by the electron microscopy. Pretreatment with aspirin and Y-20811, a thromboxane synthetase inhibitor, significantly prolonged the time required for occlusion in the guinea-pigs, while these drugs were ineffective in the rats. The antithrombotic effect of vapiprost, a thromboxane A2 receptor antagonist, was more pronounced in the guinea-pigs than the rats. In conclusion, this model in guinea-pigs is more suitable for evaluating antithrombotic drugs, particularly, the action of which is exerted involving the prostaglandin cascade. PMID- 1412223 TI - Non-specific influence of chemical modification upon the properties of antithrombin III:modification of carboxyl groups. AB - The ability of antithrombin III to inhibit thrombin was observed to be rapidly inactivated upon specific modification of carboxyl groups. The loss of activity, upon treatment with nitrotyrosyl ester in the presence of 1-cyclohexyl-3-(2 morpholinoethyl) carbodiimide metho-p-toluenesulfonate, was concomitant to the incorporation of 2 moles of nitrotyrosine per mole of inhibitor indicating the modification of only two carboxyl groups. Moreover, the modification occurred with loss, also, of the ability of the native protein to bind tightly to heparin. The modified antithrombin III retained a reduced affinity for heparin (eluting at 0.3M NaCl from heparin Agarose) and was observed to be a competitive inhibitor of the heparin-dependent rate of inhibition of thrombin by native antithrombin III. However, FAB-MS (fast atom bombardment mass spectroscopy) analysis of digests of modified material gave no indication that modification was localized to specific Asp or Glu residues. It is concluded that the loss of activity is due to deleterious change in conformation during modification. These findings, together with our previous report upon tryptophan modification of antithrombin III [1] suggest that the nature of the molecule is such that considerable care must be taken in interpretation of results when investigating the structure/function relationships of this protein by chemical modification. PMID- 1412224 TI - Studies of the platelet fibrinogen receptor in Glanzmann patients and uremic patients. AB - The purpose of the present study was to investigate the binding of fibrinogen to the platelet fibrinogen receptor. Glycoprotein (GP) IIIa was measured utilizing a fluorescein isothiocyanate (FITC)-labelled monoclonal antibody and an Ortho Spectrum III flow cytometer. The number of binding sites per platelet was calculated to be 30,200. Using this technique it appears possible not only to diagnose Glanzmann's thrombasthenia but also to identify carriers. In uremic patients a slightly lower number of GPIIIa molecules per cell than in control subjects was found. Treatment with erythropoietin had no significant effect on the expression of GPIIIa. Thrombin, and to a less extent ADP, increased the binding of FITC-conjugated fibrinogen to normal platelets but had no significant effect on the expression of GPIIIa. PMID- 1412225 TI - The response of plasma von Willebrand factor to desmopressin (DDAVP) is related to the platelet levels of von Willebrand factor. PMID- 1412226 TI - Two routine methods for antithrombin III determination. PMID- 1412227 TI - [Rehabilitation in the way of Sisyphus]. PMID- 1412228 TI - [Drugs and quality assurance in hospitals--a responsibility even for physicians]. PMID- 1412229 TI - [Posttraumatic acute renal failure]. PMID- 1412230 TI - [Lung cancer--still a sad story]. PMID- 1412231 TI - [Treatment of lumbar disk prolapse]. PMID- 1412232 TI - [Lumbar disk prolapse treated with chymopapain]. AB - We report results from 108 consecutive patients followed up for one year after chymopapain injection. The patients were selected on strict clinical and radiological criteria. In nine patients (8%) the result was poor, and they were surgically treated within one year after the injection. 99 (92%) patients improved and after one year 87 of these (81% of the total material) had returned full time to their previous occupation. The only serious complication was one case of septicemia and possible discitis. The patient made a full recovery after antibiotic treatment. On the basis of these results, we shall continue to use chymopapain injection to treat selected patients with sciatica caused by herniated lumbar discs. PMID- 1412233 TI - [New therapeutic possibilities for acquired clonal blood diseases and myelodysplasia]. AB - Examples of patients are used as a basis for discussing the treatment of severe aplastic anaemia with clonal chromosomal aberrations in haematopoietic cells, the aplastic form of paroxysmal nocturnal haemoglobinuria and myelodysplasia, with allogeneic bone marrow transplantation. Transplantation with marrow from an HLA identical sibling donor has curative potential in selected patients with these disorders. The procedure should preferably be carried out before the patients have received massive treatment for the complications of marrow failure. The use of matched unrelated bone marrow donors is still at the investigation stage. PMID- 1412234 TI - [Rehabilitation of patients with brain stem damage]. AB - We describe seven patients with serious brain stem damage who were admitted to Sunnaas Rehabilitation Hospital over a period of two years (1989-91). Our patients had quadriplegia and anarthria with some or completely preserved cognitive function. They experienced varying degrees of restitution, but all remained severely impaired. Important areas for rehabilitation include communication, alimentation, mobility, emotional reactions, medical complications and daily living arrangements. Severely impaired patients can enhance their quality of life by use of technical devices. Minimal motor function is necessary to control a switch, but preserved cognitive function is essential. PMID- 1412235 TI - [Helicobacter pylori and gastrointestinal tract diseases]. AB - We review the bacteriological, epidemiological and pathogenetic aspects of Helicobacter pylori and related diseases of the gastrointestinal tract. It is concluded that H. pylori seems to be at least one of several etiological factors for diseases such as chronic gastritis and duodenal ulcer. It may also be an important cofactor in the development of gastric carcinoma. PMID- 1412236 TI - [Diagnosis of Helicobacter pylori infection. Rapid urease test, microscopy of smears and culture from ventricular biopsy compared with the 14C-urea breath test]. AB - By employing the 14C-urea breath test as the reference method we determined the specificity and sensitivity of three bioptic methods for diagnosis of Helicobacter pylori infection in 103 subjects. All biopsy specimens were obtained from the gastric antrum. For culture the specificity was 100%. Its applicability was reduced, however, by a low sensitivity (73.8%) and a delay of several days before the final result was available. Microscopy of Loeffler-stained biopsy smears yielded a specificity of 100% and a sensitivity of 92.9%, but the method was regarded time-consuming. The rapid urease test yielded a specificity of 98.4% and a sensitivity of 85.7%. Being quick, simple and inexpensive the rapid urease test is well suited for routine use in gastroscopy. PMID- 1412237 TI - [Rhabdomyolysis in self-induced poisoning. A prospective study]. AB - In a prospective study of 103 patients hospitalized for self-poisoning the incidence of rhabdomyolysis (creatine kinase > 1000 U/l) was nearly 7%. A further 9.7% had elevated creatine kinase activity, but lower than 1000 U/l. Two patients showed clinical symptoms of rhabdomyolysis at time of admission; one after heroin and the other after salicylate intoxication. Both developed renal failure, and one of them underwent peritoneal dialysis. The high incidence of rhabdomyolysis found in the study suggests that creatine kinase activity should be considered in all cases of intoxication admitted to hospital. Rhabdomyolysis may often present no symptoms even in conscious patients, and serious complications can be limited by preventive measures if rhabdomyolysis is recognized early. PMID- 1412238 TI - [Rapidly progressing glomerulonephritis]. AB - 20 patients with rapidly progressive glomerulonephritis were treated at the nephrological section, Medical Department A, Haukeland Hospital from 1973 to 1988. Nine patients had an idiopathic type of nephritis, while seven patients had this type of glomerulonephritis secondary to systemic lupus erythematosus, endocapillary glomerulonephritis, Henoch-Schonleins purpura or Wegener's granulomatosis. Four patients had antibodies to glomerular basement membrane. All renal biopsies showed extracapillary proliferation and tubular cell damage. All patients were given immunosuppressive treatment with corticosteroids and cytotoxic drugs. Nine patients who were admitted to the hospital from 1973 to 1978 were not treated with plasmapheresis, 11 patients from 1978-1988 were all treated with plasmapheresis. After one year of observation, six of the nine patients in the first group had died, while this applied to only two in the group treated with plasmapheresis. Early diagnosis and plasma exchange, in addition to immunosuppression, seems to be the best treatment for these patients. PMID- 1412239 TI - [Ultrasonic examination of the breast]. AB - Ultrasonography can be a valuable adjunct to mammography in the evaluation of breast pathology. Breast sonography can differentiate a cyst from a tumour. Fibroadenomas and carcinomas can often present characteristic ultrasonic features but, as a rule, ultrasonography does not give a confident diagnosis of benign or malignant tumour. Ultrasound-guided needle biopsies and preoperative localization of non-palpable lesions can be performed. Breast sonography should be regarded as an adjunct to mammography. The practical role of ultrasonography in a breast imaging centre will depend on the quality of the triple diagnostics. PMID- 1412240 TI - [Prevention of acute renal failure in muscular injuries]. AB - Rhabdomyolysis may be caused by sustained, continuous pressure to skeletal muscle. The syndrome is characterized by hypovolemia, hyperkalemia and release of excessive amounts of myoglobin to the circulation. If untreated, the syndrome becomes complicated by potentially fatal acute renal failure. Two case reports are presented which illustrate the importance of early and aggressive fluid substitution where forced alkaline diuresis seemed to prevent life threatening renal complications. PMID- 1412241 TI - [Immunophenotyping of leukemias]. PMID- 1412242 TI - [A record of procedures--its use and usefulness. Evaluation of a tool for general practitioners in Telemark]. AB - A loose-leaf book of procedures has been published earlier. The aim of this evaluation was to study the use of this book in the county of Telemark, and the possible effect of the book on the quality of the letters notifying admission to hospital. A questionnaire has been sent twice to all general practitioners in Telemark. In addition, the medical directors of two hospital departments have evaluated the quality of the letters of admission before and after the distribution of the book. The results are interesting, and show that the book is widely used in the county of Telemark. PMID- 1412243 TI - [Quality assurance in hospitals. Evaluation of the old and new system for medication routines at the Sentralsjukehuset in Rogaland autumn 1990/spring 1991 and 1992]. AB - The routines for ordination and documentation of medication were found to be inadequate in our hospital. A new ordination system was introduced in 1991 based on the following principles: 1) All ordinations/seponations must be signed by a doctor. 2) Each day, all medication must be considered and signed by a doctor. 3) Ordinations by telephone must be signed later by a doctor. 4) The original ordination must be used when drugs are prepared. 5) Nurses must sign for supplied doses. The old and new system was evaluated in a medical and a surgical ward. In the medical ward the change of system had reduced errors of documentation from 20% to 1.8%, and in the surgical ward from 33% to 8%. The new ordination system has resulted in better patient documentation and has improved the hospital's written records. PMID- 1412244 TI - [Cancer in Pasvik. II. Pollution from Nikel--no relationship after all?]. AB - Previous medical investigations have indicated a connection between heavy metal pollution from the metallurgical industry in the Russian town of Nikel on the Kola peninsula and an observed increase of incidence of cancer among the Norwegian population living near the Russian border. This report contains the latest measurements of heavy metals in the local environment and discusses exposure levels in relation to possible health effects. It is concluded that exposure to heavy metals via food, water and air is considered so low as to be unlikely to cause any increase in incidence of cancer. Thus, the previously held hypothesis of a connection between heavy metal pollution from Nikel and cancer in Pasvik is not confirmed. PMID- 1412245 TI - [Functional dyspepsia--a stress disease]. PMID- 1412246 TI - [Which women should be tested for Chlamydia trachomatis in general practice?]. PMID- 1412247 TI - [Avoiding the use of not virus-inactivated plasma]. PMID- 1412248 TI - [Percutaneous central venous catheter in newborn infants]. PMID- 1412249 TI - [Admission criteria for medical studies]. PMID- 1412250 TI - [Quality assurance--where is the challenge?]. PMID- 1412251 TI - [A totally private health care system for rich patients?]. PMID- 1412252 TI - [Patients' rights with a basis in the Norwegian welfare ideology]. PMID- 1412253 TI - [Undergraduate medical education is outdated]. PMID- 1412254 TI - [The Fosen team--psychiatry in a new style]. PMID- 1412255 TI - [Mental retardation--a challenge for health services]. PMID- 1412256 TI - [Primum nil nocere (first: do no harm). Should the treatment of patients with ventricular arrhythmia be centralized?]. PMID- 1412257 TI - [Torsades de pointes ventricular tachycardia induced by disopyramide at therapeutic serum concentration]. AB - We describe a patient who developed torsades de pointes ventricular tachycardia after several years of treatment with disopyramide. The case demonstrates that measuring disopyramide serum concentration provides limited information about correct dosages. Life-threatening arrhythmias may arise even at recommended doses and therapeutic serum concentration. Clinical trials have shown that class Ic antiarrhythmic drugs, and perhaps all class I antiarrhythmics, may increase the risk of serious arrhythmias and sudden death in certain groups of patients. Aspects of the pharmacology of disopyramide are discussed, with particular emphasis on the variable plasma protein binding and the narrow therapeutic specter. This complexity seems to be the most important reason for the limited reliability of serum concentration measurements for predicting the best dosage for the individual patient. PMID- 1412258 TI - [Treatment of mentally retarded in psychiatry]. AB - The reform decentralizing the special care of the mentally retarded in Norway has caused concern within the Norwegian psychiatric community. The frequency of psychiatric disturbances and behaviour problems in this population is known to be high, and closing down special institutions may eventually direct more mentally retarded persons to psychiatric hospitals. Behaviour problems like poor communication skills, lack of social skills and self-care, and disruptive behaviours seem to cause more concern than the actual diagnosis. However, the same behaviour problems are found in psychiatric hospital populations, for instance among chronic schizophrenics. From a behaviour modification point of view these behaviours can be treated regardless of diagnosis. The article describes how a psychiatric hospital unit can apply behaviour modification resulting in a better life for an otherwise untreatable patient. It is recommended that behaviour modification techniques should be used concurrently with other methods of treatment used in psychiatry. As well as being potentially helpful to psychiatric patients, behaviour modification techniques will make psychiatry better equipped to treat mentally retarded people in need of psychiatric care. PMID- 1412260 TI - [Pregnant diabetics. A retrospective study of pregnancy and labor in women with type 1 diabetes in Sor-Rogaland 1982-90]. AB - Foetal mortality and morbidity rates are higher among pregnant diabetics than in the general population of pregnant women. From 1982 to 1990, 59 pregnant diabetics were closely supervised by a dedicated outpatient team. Throughout the pregnancies the insulin demand increased, and metabolic control improved. 78 babies were born. The perinatal mortality rate was 3.9%. Major congenital anomalies occurred in 6.4%. The presence of maternal diabetic complications was associated with a higher rate of perinatal complications. The risk of anomalies and high birth weight increased with poor metabolic control. Diabetic women of childbearing age should therefore receive advice before any planned pregnancy. PMID- 1412259 TI - [Psychiatric consultations at a somatic central hospital. Review of 383 referrals over 3 years]. AB - We present an analysis of all psychiatric consultations with inpatients in the somatic wards at the Central Hospital in Alesund over a period of three years. About 1% of the patients were referred for psychiatric consultation. Most of these patients had no previous experience of psychiatry. Mean age was 45 years (range 16-90), and 56% were females. The reasons for referral were assessment of suicidal behaviour (47%), depression (16%) and psychosis (11%). The most common psychiatric diagnoses were personality disorders (16%), affective disorders (14%) and alcohol and drug abuse and dependence (14%). About 10% were admitted to psychiatric wards, and 21% were referred to psychiatric outpatient clinics. The referring physicians were satisfied with the psychiatric consultation service. PMID- 1412261 TI - [Smoking habits of pregnant women in municipalities of Asker and Baerum]. AB - Smoking in pregnancy is unequivocally harmful to both foetal and maternal health. Earlier investigations in Norway among pregnant women who smoke have demonstrated a prevalence of smoking of around 40% and that some women stop smoking as soon as the pregnancy is confirmed (around 20%). This investigation reports only 16% smokers among pregnant women registered at 18th week of pregnancy in the two municipalities of Asker and Baerum. Average daily consumption was 8.6 cigarettes, and 65% of the women stated that they smoked more than five cigarettes per day. 97% expressed a positive interest in quitting smoking, and 76% had tried to quit earlier. 77% had a partner who was a daily smoker. An assessment of level of education showed that 82% had completed 12 years of schooling and 23% reached a higher educational level. We conclude that the relatively low incidence of daily smoking among pregnant women in these two municipalities should inspire the initiation of active intervention programmes. PMID- 1412262 TI - [Kasabach-Merritt syndrome. A differential diagnosis in thrombocytopenia]. AB - The Kasabach-Merritt syndrome consists of hemangioma in association with thrombocytopenia and localized consumption coagulopathy. It is primarily a disease of childhood, but may be seen in adult patients too. When untreated, it involves considerable risk of mortality. Two adult patients are described. The disease can be cured by surgery. We discuss different options for treatment when surgery is not feasible. PMID- 1412263 TI - [Abdominal wall hematoma]. AB - We describe three case reports of hematomas in the abdominal wall muscles and discuss etiology, diagnostic findings and treatment. Abdominal wall hematomas are uncommon, and the condition is often misdiagnosed. One of our patients was laparotomised owing to suspected appendicitis, and one patient presented a tuberculous abscess that may have been an infected hematoma. Ultrasonographic examination or CT gives the correct diagnose. Conservative management is the treatment of choice unless bleeding is severe or the course is complicated by infection. PMID- 1412264 TI - [Insulin pen in the treatment of childhood diabetes]. AB - 37 diabetic children changed from insulin syringes, with individually adapted mixtures of rapid and intermediate acting insulin, to a regimen involving use of an insulin pen (Insuject, Novo Nordisk, Copenhagen) and standard insulin mixtures. During the study an attempt was made to arrive at an optimal regimen for each child by selecting from among the following available insulin preparations (proportion rapid/intermediate acting in parentheses): Velosulin (100/0), Initard (50/50), Mixtard (30/70), Combitard (15/85), and Insulatard (0/100). The 35 families who completed the one-year study maintained that the Insuject pen made the injection procedure much easier. The pen proved to motivate the children to perform the injection without help. No effort was made to increase the number of daily injections, but seven families changed from two to three daily doses on their own initiative. The HbAlc at zero, three, six, nine and 12 months were as follows (SD in parentheses): 7.5 (1.2); 7.9 (1.5); 7.6 (1.2); 7.8 (1.4); and 7.9 (2.1). We conclude that the Insuject insulin pen is a safe and reliable instrument in childhood diabetes. Good metabolic control can be obtained with commercial insulin mixtures given 2-3 times daily. PMID- 1412265 TI - [Failed induced abortion. Pregnancy continuing after induced abortion]. AB - Operations classified as induced abortion fail, i.e. the pregnancy continues, in approximately 0.05% of the cases. Termination procedures before 7-8 weeks of gestation and wrong assessment of the size of the uterus imply significantly increased risk of failed abortion. The article describes current methods for early termination of pregnancy, as well as preoperative procedures and postoperative advice aimed at avoiding or detecting failed induced abortions. PMID- 1412266 TI - [Medical undergraduate education is outdated. From the interns' point of view]. AB - This survey is based on a questionnaire sent to all 517 interns in Norway in December 1990, of whom 93% replied. Ten interns were interviewed personally. The majority felt they received a good theoretical basis during their medical studies, but less than a third stated that the education had adequate vocational orientation. Students from the University of Tromso, were the exception in this respect. They were more positive towards the vocational aspects of their studies. Most interns had high expectations with regard to learning during internship, and half of them to have to face various traumatic experiences during this period. One out of two stated that, so far, their internship training had been inspiring for their career as medical practitioner. About a third replied that they doubted whether they would choose the same profession if they were to make this decision again. The results of this study emphasize the importance of the current changes in the curriculum at all four medical faculties in Norway. The results also suggest a need for better coordination of university studies and internship, and more structured teaching during the internship. PMID- 1412267 TI - [Professionalization without management? A study of the scientific content during the internship]. AB - The basic medical education in Norway ends with one year as house physician or surgeon and six months as assistant to general practitioner. This internship is an important period in the course of education leading to a medical degree. According to a new national standard issued in 1989 all interns should have a personal supervisor and a formal curriculum covering this period. The present survey was carried out in order to evaluate the quality of learning during internship as experienced by the trainees. A questionnaire was sent to all 517 Norwegian interns as of December 1990. 93% replied. Ten of the interns were interviewed personally. 34% of the house officers had an appointed supervisor compared with 54% in primary care. Few of the interns had a formal curriculum. Many of them felt the need for constructive feedback on their professional performance, but few received it. They nevertheless claimed that it was easy both to raise questions and to obtain assistance in solving medical problems. One out of six interns had been severely depressed during the period of internship and related this to experiences at work. Women were generally more sensitive than men in this respect and were more critical of the interpersonal relationships experienced during this period. Despite the new standard, which sets realistic and necessary goals for this part of the medical education, learning during internship is still much a matter of chance. It is a major challenge to the medical profession to take the needs of young medical practitioners seriously. PMID- 1412268 TI - [Quality assurance, internal control and patients' security]. AB - Quality assurance of health services includes elements of both medicine and law. The professional standard has to be defined by the medical establishment, while the legislation points out the duties that have to be discharged in order to obtain the goal of quality and a high standard of health care. A superior goal in all health care is to offer the patients adequate medical treatment. The patients' rights usually correspond to the duties of the providers of the care, and in order to satisfy the patients' requirements it is important to ensure that these providers fulfill their duties. PMID- 1412269 TI - [Ergotherapy--more than stimulation of activities]. AB - There are many ways of forming a caring relationship. One way is to give people the opportunity to be active, whether they have a long or a short time left to live, and irrespective of intelligence, skills, values or cultural background. The occupational therapist focuses on and emphasizes the patients' need to master their environment and stresses a person's sense of self, bringing out what she or he feels is essential to be a competent person. Quality of life depends on an internal feeling of personal worth. By being able to contribute even on a small scale, for example by making a little gift to a friend, a person may gain both self-respect and the admiration of others. PMID- 1412271 TI - [Adverse effects and the press]. PMID- 1412270 TI - [Administration of propofol (Diprivan) to children]. PMID- 1412273 TI - [Deep sighs or heretical reflections on diabetes]. PMID- 1412272 TI - [How to differentiate myelogenous leukemia FAB-type 6 (erythroleukemia) from the myelodysplastic syndrome?]. PMID- 1412274 TI - [Professional secrecy, what is it worth?]. PMID- 1412275 TI - [On the difference between draining the cup and washing one's hands]. PMID- 1412276 TI - [Support good self concept in employees receiving dismissal notice and those affected by company merging]. PMID- 1412277 TI - [Information and support to cancer patients]. PMID- 1412278 TI - [Distribution of physicians--with intentional prejudice?]. PMID- 1412279 TI - [International activities of the Norwegian Medical Society]. PMID- 1412280 TI - [Use of drugs without an approved indication]. PMID- 1412281 TI - [Treatment with botulinum toxin--a new and effective therapy]. PMID- 1412282 TI - [Psychiatric diagnosis]. PMID- 1412283 TI - [Classification systems in theory and practice. The National Social Insurance Board demands the ICPC codes from 1 October 1992]. PMID- 1412284 TI - [Surgical treatment of abdominal aortic aneurysms. Risk factors and complications]. AB - Between January 1985 and April 1991 156 patients underwent surgery for abdominal aortic aneurysm at Nordland Regional Hospital. Of these, 90 underwent elective surgery; 36 were operated on for symptomatic aneurysm; 30 for ruptured aneurysm. The mortality rates were respectively 10%, 14% and 47%. Surgery for aortic aneurysm is on the increase. Advanced age, and associated serious cardiac disease predispose to postoperative complications and death. To reduce mortality better preoperative evaluation and treatment are essential. PMID- 1412285 TI - [Aortic aneurysm misinterpreted as pulmonary tumor]. AB - Two cases have been reported of patients with an atherosclerotic saccular aneurysm of the descending aorta which simulated a left-sided lung neoplasm. Despite advanced diagnostic procedures, the diagnosis was not made before thoracotomy. The authors discuss some of the diagnostic problems related to thoracic saccular aneurysms. PMID- 1412286 TI - [Abdominal aortic surgery. Transperitoneal or retroperitoneal approach?]. AB - During the past five years a retroperitoneal approach was used in 34 patients and the transabdominal route in 49 patients for treatment of abdominal aortosclerosis. Both groups were identical with respect to age, sex and preoperative morbidity. In patients with previous laparotomy the retroperitoneal approach was always chosen. There was no significant difference with regard to postoperative complications. The only significant difference between the two groups after the operation was a trend towards earlier defecation among the patients treated by the retroperitoneal approach. We can not demonstrate any important advantage or disadvantage of the retroperitoneal approach. The transabdominal approach provides an opportunity to examine the abdominal organs for malignancy. We found one asymptomatic gastric cancer. The retroperitoneal approach is particularly suitable in patients who have undergone laparotomy before for expected severe abdominal adhesions. PMID- 1412287 TI - [Surgical treatment of aortic occlusion and obliterating aorto-iliac arteriosclerosis]. AB - From 1985 to March 1991, 83 patients with the diagnosis aortoiliac obliteration and aortic occlusion were operated on at the Department of Surgery, Nordland Central Hospital. The main symptom was claudicatio intermittens. 16 patients had pain while at rest, and two had gangrene. The surgical technique was either Y prosthesis or thrombendarterectomy. Four patients (4.8%) died postoperatively, three of myocardial infarction and one of intestinal ischemia and peritonitis. In our study 66 patients with aortoiliacal atherosclerosis were compared with 17 patients with aortic occlusion. Patients with aortoiliacal atherosclerosis demonstrated by angiography had much more severe infrainguinal arterial pathology. In the occlusion group the postoperative outcome, as measured by ankle/brachial index, was significantly better (p < 0.01). The study included four female patients less than 50 years of age with total infrarenal aortic occlusion. Their symptoms and signs are discussed. PMID- 1412288 TI - [Surgical treatment of acute intestinal ischemia. Successful treatment with embolectomy of the superior mesenteric artery]. AB - We describe a patient with acute intestinal ischemia successfully treated with embolectomy of the superior mesenteric artery. Over the last four years, 11 patients with the same disease were treated with bowel resection at Nordland Regional Hospital. The mortality rate after bowel resection was 45%. Long duration of symptoms, and high frequency of associated cardiovascular disease was characteristic. In elderly patients with acute abdominal pain and cardiovascular disease, a diagnosis of acute mesenterial ischemia should be seriously considered. In patients with acute mesenteric ischemia and no bowel necrosis, embolectomy must be considered in preference to bowel resection. PMID- 1412289 TI - [Familial hypercholesterolemia--intensive diet therapy combined with drug therapy]. AB - The aim of the investigation was twofold: to study the effect of lovastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, alone and in combination with other lipid lowering drugs in an open 48 week single centre study, and to study if lipid lowering drugs influence adherence to diet in adult patients with familial hypercholesterolemia. Lovastatin monotherapy (80 mg daily) for 12 weeks reduced serum cholesterol, LDL-cholesterol and triglycerides levels by 36%, 44% and 24% respectively. HDL-cholesterol level was increased by 12%. The addition of 16 g cholestyramine daily further increased the reduction of total cholesterol and LDL-cholesterol levels by 17% and 24% respectively. Addition of 1 g probucol daily decreased total cholesterol, LDL-cholesterol and HDL-cholesterol levels by 9%, 5% and 27% respectively. Addition of omega-3-fatty acids (3.6 g daily) reduced total cholesterol, LDL-cholesterol and triglycerides levels by 10%, 12% and 20% respectively. Administration of potent lipid lowering agents did not influence adherence to a diet with a mean daily fat energy of 21% (CI: 20 22), cholesterol of 177 mg (CI: 157-196) and P/S ratio of 0.75 (CI: 0.66-0.84). A significant increase in liver enzymes was recorded in only one patient. One patient was withdrawn from the study because of myositis. PMID- 1412290 TI - [Inadequate treatment of affective disorders]. AB - Inadequate treatment of mood (affective) disorders is related to the mind/body dualism, desinformation about methods of treatment, the stigma of psychiatry, low funding of psychiatric research, low educational priority, and slow acquisition of new knowledge of psychiatry. The "respectable minority rule" has often been accepted without regard to the international expertise, and the consequences of undertreatment have not been weighed against the benefits of optimal treatment. The risk of chronicity increases with delayed treatment, and inadequately treated affective disorders are a leading cause of suicide. During the past 20 years the increase in suicide mortality in Norway has been the second largest in the world. Severe mood disorders are often misclassified as schizophrenia or other non affective psychoses. Atypical mood disorders, notably rapid cycling and bipolar mixed states, are often diagnosed as personality, adjustment, conduct, attention deficit, or anxiety disorders, and even mental retardation. Neuroleptic drugs may suppress the most disturbing features of mood disorders, a fact often misinterpreted as supporting the diagnosis of a schizophrenia-like disorder. Treatment with neuroleptics is not sufficient, however, and serious side effects may often occur. The consequences are too often social break-down and post depression syndrome. PMID- 1412291 TI - [ICPC in general practice]. AB - The aim of this pilot study was to describe the distribution of diagnoses in general practice using International Classification of Primary Care (ICPC). The study took place in a group practice in Kongsberg, Southern Norway, in May 1991. It was of particular interest to find out how often doctors could use a disease as diagnosis (ICPC component 7) after the meeting with the patient and how often they used a symptom or complaint (ICPC component 1) as diagnosis. Results from 1,189 consultations show that a disease was used as diagnosis in 61% of all cases. A complaint or a symptom was used in 21%. Women were more often given a symptom as diagnosis. The study also shows that disorders of the respiratory and musculoskeletal systems were the most common diagnoses, accounting for 18% and 16% respectively. During one month, 247 diagnoses were used. Inter-observer tests of reliability showed that 81% of all consultations were coded to the same chapter. PMID- 1412293 TI - [Use of propofol in Norwegian hospitals]. AB - Propofol is approved by the Norwegian authorities (The Norwegian Medicine Control Authority) only for anaesthesia for less than three hours in adults. 54% of Norwegian hospitals had used propofol for anaesthesia in children and 33% for anaesthesia of more than three hours duration. In hospitals with an intensive care unit, 66% had used it for sedation in adults, 24% in children. It is not illegal to use a drug without the approval of the control authority, but the sedation of children had taken place without a basis in scientific documentation. The market for propofol fell by 40% shortly after the media focused on possible severe side effects in sedated children. Many of the anaesthesiologists found the media focus useful, but many thought that it was incorrect, and most of them that it was too general. PMID- 1412292 TI - [Botulinum toxin treatment of spastic torticollis]. AB - Botulinum toxin A was administered to 19 patients with spasmodic torticollis. A significant decrease of abnormal head and neck movements was recorded, and all the patients who suffered pain reported relief. Side effects were minor and transient. The results of this study indicate that botulinum toxin is an effective means of treating torticollis. PMID- 1412294 TI - [Quality adjustment of life years--possibilities, limitations, alternatives]. AB - QALYs express the sum of individual utility gains from medical interventions. As such they are potentially a useful measure in deciding how to allocate resources. They should not, however, be equated with the overall value that society places on different health care programmes. The latter is determined not only by the number of QALYs gained, but also by a series of distributional and ethical considerations. This should be made clear in the presentation of QALY calculations, particularly in cost-per-QALY league tables. More comprehensive measures of social value that may be used in cost-utility studies need investigating. PMID- 1412295 TI - [Administration of propofol (Diprivan) to children]. PMID- 1412296 TI - [Treatment of hypertension in the elderly]. PMID- 1412298 TI - [Law on patients' rights]. PMID- 1412297 TI - [The significance of chromium for metabolic cardiovascular syndrome]. PMID- 1412299 TI - [The role of health care missions in the health care of developing countries- history and future]. PMID- 1412300 TI - [Views in Norwegian psychiatry]. PMID- 1412301 TI - [Prioritizing in health care--how to go further?]. PMID- 1412302 TI - [Strategies for cardiovascular diseases]. PMID- 1412303 TI - [Resistance problems in developed and developing countries]. PMID- 1412304 TI - [Resistance problems in developing countries--use and misuse of antiinfective agents]. AB - Widespread use and misuse of antiinfectiva have resulted in a problem of drug resistance linked to treatment of infectious diseases. In developing countries especially, the sale of such drugs is poorly controlled and the pharmaceutical industry is dumping obsolete products. Intensive marketing, lack of diagnostic facilities and receptive local cultural attitudes to new "wonder drugs" such as antibiotics, have resulted in dramatic unnecessary use of such. Therefore the ideal strategies for treatment of infectious diseases guided by microbiological diagnosis and resistance pattern are violated in most developing countries, leading to excessive use of antiinfectiva and development of resistance. This has serious consequences for the infections that cause most cases of infant mortality, namely malaria, diarrhoeas and infections of the respiratory tract. Improvements in this vicious circle of drug use and resistance can only be made by attacking several factors simultaneously. There is a need for general information, stricter legislation, essential drug lists, national drug policies, better knowledge of local resistance patterns, better diagnostic facilities, better knowledge about local beliefs about drugs and better communication to local health workers and the community. PMID- 1412305 TI - [Bacteriological examination of bronchial aspirates obtained via fiberoptic bronchoscopy]. AB - We present the bacteriological findings in 329 aspirates from fiberoptic bronchoscopy. Quantitative cultures were not performed. 92 of the patients had radiologically confirmed pneumonia, 58 possibly had infectious bronchitis or pneumonia which was not verified radiologically, 154 had other pulmonary diseases and 25 had no verified pulmonary disease. 13% of aspirates contained no bacterial isolates and 33% revealed growth of multiple bacteria, classified as "normal pharyngeal flora". Among the 54% with specified bacterial findings the most frequent bacteria were viridans streptococci, staphylococci, Haemophilus influenzae, and Streptococcus pneumoniae. The differences in bacterial flora between the patient groups were only minimal. Klebsiella and Escherichia coli were the only bacteria indicating presence of pneumonia. S pneumoniae were found more frequently among patients with no signs of infection. Bronchial aspirates obtained with a fiberbronchoscope may give false positive results and are of limited value in diagnosing pneumonia. However, the presence of gram negative intestinal rods may indicate bacterial respiratory infection in hospitalized patients. Improving sampling and culture techniques can possibly improve the value of bacteriological findings. PMID- 1412306 TI - [Lower respiratory tract infections among the elderly in Finnoy municipality. A retrospective study of the incidence, treatment and outcome]. AB - Based on a retrospective study of the case records of the primary health care services in a small Norwegian coastal community (Finnoy), we found an incidence of 13% for lower respiratory infections in persons aged 70 years or more. Most often the initial medication was penicillin. In 23% of recorded episodes, medication was changed, owing to unsatisfactory response. Overall mortality in the group was 9%. Three out of five deaths occurred in patients terminally ill from other diseases at the time the respiratory infection started. Problems related to diagnosis, management and prevention are discussed. PMID- 1412307 TI - [Pseudomembranous colitis. Surgical treatment]. AB - Pseudomembranous colitis is an inflammatory intestinal disease that is usually secondary to antibiotic treatment. The disease upsets the normal bacterial flora of the large intestine. Therapy consists of fluid replacement, discontinuation of broad-spectrum antibiotics and treatment with vancomycin or metronidazole. In severe or resistant cases surgical treatment is required. We describe one case history and give some guidelines for surgical treatment. PMID- 1412308 TI - [Local resection of cancer of the Vater's papilla]. AB - Tumours of the papilla of Vater are almost always adenocarcinomas and are often less than 2.5 cm in diameter. Lymph node metastases occur in one fourth of the patients with tumours with a diameter of less than 2.5 cm. Whipple's procedure has been the most common operation when attempting radical excision. Local resection has not won acclaim, even though the five year survival rates are often reported to be about the same as for Whipple's procedure. We present a patient who was operated on by local resection, and describe the operative technique. PMID- 1412309 TI - [Necrosis of the small intestine. A diagnostic and therapeutic challenge]. AB - The paper describes three patients with small intestinal necrosis from different causes: One patient had diabetes, and severe ketoacidosis, which may cause microthrombosis in small intestinal vessels. This patient died in septic shock during laparotomy, removing the necrotic gut. The second patient was laparotomized because of free air in the abdomen originating from a clostridial intestinal infection. The third patient caught a salmonella infection during a holiday in the Canaries, thereafter peritonitis due to small intestinal necrosis. These three patients illustrate principal aspects of the surgical management of patients with intestinal necrosis. Firstly, necrotic intestinal segments must be removed as soon as possible. Delay represents a threat to the patient's life in all situations when intestinal segments are devascularized. Secondly, relaparotomy may be mandatory in clostridial intra-abdominal infections. We report these patients to illustrate that well known surgical principles may be life-saving if effectuated without delay. This applies also in the case of patients with uncommon diseases and complications. PMID- 1412310 TI - [Examination and treatment of gynecological bleeding disorders]. AB - The investigation and treatment of gynaecological dysfunctional bleeding has remained largely unchanged since the problem was dealt with in a special issue of the Journal of the Norwegian Medical Association in 1976, in spite of the advent of modalities like endometrial cytology, hysteroscopy and vaginal ultrasonography, as well as knowledge about the relative lack of efficiency of dilatation and curettage in the investigation and treatment of the condition. We describe a modern programme for investigation and treatment of gynaecological dysfunctional bleeding. The programme relies on clinical assessment combined with medical therapy, with optional use of modern investigative modalities when indicated. In a strictly controlled outpatient programme the need for dilatation and curettage can be greatly reduced without jeopardizing the safety of the patient. PMID- 1412311 TI - [Selection by consequences]. AB - Selection made on the basis of consequences is a causal mode found only in "living" things. Selection happens at the level of species, individual and culture. Human behaviour is the joint product of the contingencies of existence responsible for natural selection and of contingencies by which the behaviour of individuals are selected, including the contingencies maintained by an evolved social environment. Behaviour is not caused by immaterial processes inside the organism. It is the contingencies for behaviour and the behaviour itself that have to be analysed, and possibly changed. The implications for treatment may be great. PMID- 1412312 TI - [Triglycerides, HDL and coronary disease. Consensus conference: National Institutes of Health 1992]. AB - The article describes the conclusions and recommendations of the panel. A review of the information on HDL-cholesterol and coronary heart disease provides considerable evidence of a causal relationship. In the case of serum triglycerides, the data are ambiguous; although strong associations are found in some studies, evidence of a causal relation is still incomplete. Seen in relation to the latest Norwegian programme for treatment of hypercholesterolemia in adults, greater emphasis should be placed on measuring HDL-cholesterol. A complete initial lipid profile should also include determination of serum triglycerides. When taking these factors into consideration, the present Norwegian recommendations seem to be appropriate for evaluating and treating hyperlipidemia. PMID- 1412313 TI - [Who is long-term sick-listed in Norway? From the project Evaluation of the follow-up of long-term sick-listed]. AB - The aim of the study was to analyse the characteristics of persons with long-term sickness certification at the end of 1990 in Norway. The study was based on data registered by the National Insurance Administration: Age, sex, place of residence, diagnoses, and prognosis as registered on Sickness certificate II. At the end of 1990 a total of 57,567 persons had been incapacitated for work for longer than eight weeks and up to 52 weeks. The prevalence was 27.9 per 1,000 employed persons, with a significantly higher prevalence among women than among men. 25% of the women certified as sick were 40-49 years old. The highest prevalence of long-term certification of sickness was found in the counties Finnmark and Troms in Northern Norway, and Hedmark in central Norway. In cases of long-term sickness certification, the most common diagnoses were musculoskeletal/connective tissue diseases and mental disorders, with a prevalence of 9.3 and 3.1 per 1,000 employed persons respectively. The study indicates the possibility of using data from existing administrative population registers to provide information on the epidemiology of long-term sickness certification in Norway. It is necessary to further improve the validity of the data. PMID- 1412314 TI - [Psychiatry in newspapers]. PMID- 1412315 TI - [Submitting of medical records to the courts]. PMID- 1412316 TI - [Behavior is formed and selected by consequences. The psyche is not suitable as explanation of behavior]. PMID- 1412317 TI - [Emergency medicine in sparsely inhabited regions]. PMID- 1412318 TI - [Sugar molecules, cell adhesion and cancer etiology]. PMID- 1412319 TI - [Occupation and smoking as risk factors for obstructive lung disease]. PMID- 1412320 TI - [Obstructive lung disease in a Norwegian population group--risk factors and occurrence]. AB - In an ordinary Norwegian population which we studied, one in 13 persons suffered from an obstructive lung disease--bronchial asthma or chronic obstructive lung disease. The prevalence of the disease was the same in both sexes, but increased with age. There was a strong association between smoking and the disease. Occupational airborne pollution was an important risk factor. Taking the longest job held as a basis for the study, the adjusted odds ratio for obstructive lung disease in those exposed to a high degree of airborne pollution was 2.5 relative to those not so exposed. There was no difference between urban and rural areas in the frequency of the disease. Allergy and bronchial hypersensitivity were both associated with obstructive lung disease. Greater efforts should be put than at present into preventing obstructive lung disease. PMID- 1412321 TI - [Pneumocystis carinii pneumonia--not only in AIDS]. AB - Two patients with haematologic malignancies developed Pneumocystis carinii pneumonia while under outpatient treatment, one on busulphan for chronic myelogen leukemia, and the other on prednisone plus chlorambucil for non-Hodgkin's lymphoma. The first patient was moderately ill and required hospitalization for 12 days while the second patient was critically ill and needed assisted ventilation for two weeks. Eventually they both recovered and returned to work. Tests for serum antibodies to the human immunodeficiency virus (HIV) were negative in both patients. We review the problem of P. carinii pneumonia in patients receiving immunosuppressive drugs. PMID- 1412322 TI - [Percentage of body fat and risk factors of coronary heart disease]. AB - This study is a cross sectional analysis using measurement of the relative amount of fat on the right upper arm by means of the near infra-red method (NIR) and computerised calculation of the percent body fat by the use of the Futrex 5000. The total sample consisted of 1,988 subjects (942 women and 1,046 men) in the two age groups 40-42 years (n = 1,180) and 65-67 years (n = 808). Average percentage of relative fat in the total sample was 26.7, average percentage of body fat was 26.5 and average Body Mass Index, BMI (kg/m2) was 24.4. The percentage of fat and the BMI would both appear to increase with age and be higher in non-smokers. The BMI was higher in men, while the percentage of body fat was higher in women. A relatively weak correlation was found between the relative amount of fat and the BMI (0.4 < or = r < or = 0.57) but there was a relatively strong correlation between the percentage of fat and the BMI (0.72 < or = r < or = 0.88). The correlation with total cholesterol, triglycerides, blood pressure (SBP, DBP, MAP) and susceptibility to cardiac infarction (calculated estimated units) was similar for both the percentage of fat and the BMI. All correlations were positive, but with a relatively low r (0.05 < or = r < or = 0.39). The interaction between the percentage of body fat and the BMI would appear to be independent of age and sex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412323 TI - [Diagnostic imaging of the gastrointestinal and biliary tracts. Pattern of examinations during the period 1975-90]. AB - The procedures used for imaging of the gastrointestinal tract, the gall bladder and the bile ducts were registered in six Norwegian hospitals during the period 1975-90. Data obtained from all hospitals showed a significant decrease in radiological examinations of the stomach and the large bowel, and a dramatic decrease of such examinations in the case of the gall bladder and bile ducts. The changes are mainly due to the increasing use of newer methods such as ultrasonography, gastroscopy and colonoscopy. The shift in the pattern of examinations, as shown in the present study, may well have many implications for patients and for the health service as a whole. PMID- 1412324 TI - [Subcutaneous emphysema in gastrointestinal tract perforation]. AB - Perforation of the gastrointestinal tract can lead to retroperitoneal abscess formation. Clinical signs and symptoms are often non-characteristic. In undetected cases the first sign of perforation may be subcutaneous emphysema. The place where this first appears correlates with the localization of the perforation. The pathogenetic mechanisms and clinical features are discussed, with reference to a case report. PMID- 1412325 TI - [Abdominal actinomycosis. Actinomycotic abscess 10 years after appendectomy]. AB - A case of actinomycosis of the abdomen ten years after surgery for acute appendicitis is reported. The patient, a 2 1/2 years old girl at the time of operation, presented with acute abdominal pain ten years after appendectomy. Computed tomography (CT) showed a mass in the region of the right psoas muscle. Fine needle aspiration revealed pus which on culture was found to contain Actinomyces israeli. Since surgery is a well known probable cause of abdominal actinomycosis, we must assume the appendectomy and the formation of the actinomycotic abscess to be related. Discovery of an abdominal mass even years after violation of the gastrointestinal tract should arouse suspicion of an abscess involving these otherwise infrequent pathogens. PMID- 1412326 TI - [Cell surface carbohydrates are involved in various biological processes]. AB - All human cells show carbohydrate structures on the surface. New knowledge about the genetic mechanisms for the synthesis of these carbohydrates and the generation of monoclonal antibodies with high specificity shows that carbohydrates are involved in various cell-cell and cell-matrix interactions. For instance, cell surface carbohydrates seem to be important in connection with fertilization, embryonic development, cell differentiation, cancer, adhesion of microorganisms and immunological processes. This new knowledge will increase our understanding of various biological phenomena, and will thus be of value for diagnosis and treatment of various diseases. PMID- 1412327 TI - [Cyclosporine in the treatment of psoriasis]. AB - Psoriasis is a chronic inflammatory skin disease of unknown etiology. An immune reaction mediated by T lymphocytes is important in the pathogenesis. Cyclosporin is a selective immuno-suppressant that inhibits helper T lymphocytes. Several controlled clinical studies have shown that cyclosporin is highly effective in controlling severe psoriasis. The main side effects are hypertension, nephrotoxicity and increased risk of developing malignancies, particularly after long-term treatment. Side effects during short-term therapy appear to be reversible. Some questions connected to the long-term use and safety of cyclosporin are still unsolved. PMID- 1412328 TI - [Streptococci group B and pregnancy. Need for routine check-ups?]. AB - Group B streptococci are a major cause of perinatal infections and affect 1-5 infants out of every 1,000 live births. Maternal vaginal colonization with these bacteria is common (5-25%), and has been associated with late abortions, foetal growth retardation, early rupture of membranes and premature delivery. Colonization with group B streptococci may be observed in more than 70% of neonates born to mothers with the bacteria in their vaginal tracts at delivery. A high number of bacteria in the maternal urogenital tract during pregnancy may predispose to early-onset disease in neonates. The estimated attack rate in colonized neonates is 1-2%. A high specific IgG antibody concentration in the mother may protect the infant, but probably not before 32 weeks of gestation. Colonized women who are unable to produce such antibodies risk having affected offspring. Neonatal infection with group B streptococci frequently results in death or permanent neurologic morbidity; especially from the early-onset type (case-fatality more than 50%) which is most often vertical transmitted. Four cases with early-onset disease illustrate the severity of perinatal group B streptococcal infections. The severity and outcome of the disease may be moderated by screening for group B streptococci during late pregnancy. This screening must be combined with special attention to irregularities in pregnancy or perinatal complications. PMID- 1412329 TI - [Cardiopulmonary resuscitation performed by laymen--the Nord-Gudbrandsdal Project -circulatory arrest in sparsely populated regions]. AB - Previous investigations from densely populated areas have shown that more patients with prehospital circulatory arrest caused by ischemic heart disease can be successfully treated by strengthening a chain of survival. This chain consists of immediate alarm followed by prompt cardiopulmonary resuscitation, early defibrillation and advanced medical support before transportation to hospital. This paper describes the methods used in the training of lay people in cardiopulmonary resuscitation, as well as how ambulance personnel were trained to use a semiautomatic defibrillator. During the period 1987-89 11.7% of the inhabitants in Nord-Gudbrandsdal attended a course in heart lung resuscitation and all the ambulance personnel were trained and certified to use Heartstart 2000 semiautomatic defibrillators. PMID- 1412331 TI - [Centralization of obstetric care and perinatal mortality in Norwegian counties 1986-90. Analysis based on public statistics from the medical birth registry]. AB - The relationship between centralization of obstetric care and perinatal mortality was studied in 19 Norwegian counties for the period 1986-90. No significant trend was found. However, during the period 1988-1990 prenatal mortality was significantly higher, with a relative risk of 1.21 (95% confidence interval 1.00 1.45), in the three counties with only one obstetric department than it was in all other counties. The analysis did not support the notion that greater centralization of obstetric care would decrease perinatal mortality. PMID- 1412330 TI - [Results of treatment--the Nord-Gudbrandsdal Project--circulatory collapse in sparsely populated regions]. AB - In Project Nord-Gudbrandsdal we aimed to reduce prehospital mortality from myocardial infarction in a sparsely populated area. The ambulance system consisted of local ambulances with semi-automatic defibrillators (the ambulance personnel were trained in the use of these), combined with advanced medical support from the local doctor and/or the air ambulance doctor. During the three year period (1987-89) 75 prehospital cardiac arrests were observed in a population of 22,000 inhabitants. 12 patients with ventricular fibrillation were defibrillated, and eight primarily with success. Four patients were discharged from hospital in a satisfactory condition. We discuss the factors determining successful resuscitation. PMID- 1412332 TI - [On liposuction and madness]. PMID- 1412333 TI - [Antihypertensive treatment with relative lopsidedness]. PMID- 1412334 TI - [Little more about the SI units]. PMID- 1412335 TI - [Basic medical education is out of date]. PMID- 1412336 TI - [Humans are the subjects for treatment. However, the cancer patient and his problems are often ignored in the process]. PMID- 1412337 TI - [Strategy for quality medicine]. PMID- 1412338 TI - [Quality assurance--an art of balancing]. PMID- 1412339 TI - [Physicians and leadership]. PMID- 1412340 TI - [Can type 1 diabetes be prevented?]. PMID- 1412341 TI - [Do physicians not examine patients with bad backs?]. PMID- 1412342 TI - [Embolization of bronchial arteries in severe and recurrent hemoptysis]. AB - Bronchial artery embolization is an established treatment for massive and serious haemoptysis. We review etiology, pathogenesis and different treatment modalities of major haemoptysis, and discuss indications and outcome. Massive haemoptysis, defined as > 300 ml/24 hrs., is a rare condition with a high mortality rate (30 80%) if treated conservatively. We describe seven patients treated with bronchial artery embolization. Three patients had massive haemoptysis, and four patients were treated for recurrent and severe haemoptysis. Two patients had haemorrhage because of inactive tuberculosis, five had cystic fibrosis. All patients were successfully treated by embolization, one patient suffered recurrent haemoptysis after four weeks. The other patients have shown no further haemoptysis during the observation period (mean 20 months). No complications were observed other than the common, self-limited post-embolization syndrome (mild fever and chest pain). In patients with severely reduced lung function and progressive disease, recurrent haemoptysis of even smaller amounts might interfere with postural drainage and cause infections and deteriorate lung function. Bronchial artery embolization should be considered for these patients as well. Unless localized lesions can be cured through surgical resection, we consider bronchial artery embolization to be the treatment of choice. PMID- 1412343 TI - [Etiology and diagnosis of chronic shoulder pain]. AB - Shoulder pain of more than three months' duration is regarded as chronic. Activity with an elevated arm is a risk factor, due to reduced local flow of blood to the supraspinatus muscle. Knowledge about normal shoulder biomechanics and dysfunctional behaviour patterns is essential when treating patients with chronic pain. It is necessary to consider psychosocial factors in addition to local pathology. The clinical examination should enable the physician to distinguish between referred and true shoulder pain and between restricted and free passive range of movement. Diagnoses may be classified into eight groups. The association between pain and degenerative changes has yet to be solved. This emphasizes the danger of deciding treatment without matching findings from radiological examinations with clinical signs and symptoms. PMID- 1412344 TI - [Indications for surgery in ulcerative colitis. Some aspects of a hospital case load]. AB - From 1.1.1985 to 1.1.1992, 233 patients with ulcerative colitis were treated in the Medical Department, Aker Hospital. 30 patients (12.9%) were referred for surgery. The main indications for surgery were severe colitis and chronic persisting symptoms. The increased risk of developing colorectal carcinoma in cases of long-standing extensive ulcerative colitis is generally accepted. Many of our unoperated patients belong to this risk group. In the present sample the resection rate was lower than recently reported from Sweden and Denmark. Symptomatic patients in the risk group for developing colorectal carcinoma should be offered surgery more liberally, and asymptomatic patients in this group should be offered colonoscopic surveillance. PMID- 1412345 TI - [Skin tests with Pityrosporum ovale extract in atopic dermatitis]. AB - The etiology of atopic dermatitis is multifactorial. Immediate-type sensitivity to the lipophilic yeast, Pityrosporum ovale, may be important, especially in a subgroup of patients with dermatitis predominantly in the head and neck region. 100 patients with atopic dermatitis were investigated by means of skin prick tests, including Pityrosporum ovale extract. Positive tests were found more often in atopic patients with "head and neck"-dermatitis, but the correlation between a positive prick test to Pityrosporum and the severity of atopic dermatitis, estimated by means of clinical criteria and total IgE, was even higher. PMID- 1412346 TI - [Quality assurance of medical leadership]. AB - Quality assurance is a managerial responsibility, but the medical management itself must also be quality assured. Today quality assurance of medical management is usually performed when the organization is not functioning properly, but quality assurance should be a continuous process. Regular feedback to the management is essential from all levels of the organization. Standards must be established for good medical management. The medical profession must start this work now. There are many others who want to take it over. PMID- 1412347 TI - [Quality assurance in psychiatry--is it possible?]. AB - The assessment of quality depends on the eye of the beholder, the patient, the clinician and his colleagues or society/third party payers. There are already several structures that regulate quality: training requirements, judicial control commissions and public health authorities, and in psychiatry also individual supervision and extensive clinical meetings. Most clinical parameters in psychiatry are measurable, but there remains the elusiveness of mental processes, which often defies quantification. Levels of symptoms and functioning, however, can be scored. Computerisation of macro-data often permits useful comparisons, as may consensus conferences and consultations with peers. The essence of quality monitoring is to find indicators that predict results and also reflect the most important situations and problems. PMID- 1412348 TI - [Routine determination of homocysteine in plasma. A new and improved possibility for risk evaluation and diagnosis of common diseases]. AB - The performance of a rapid, fully automated HPLC assay for total homocysteine in plasma has made it possible to offer this analysis as a routine laboratory test. The reference interval in fasting individuals is 7-14 mumol/l. In EDTA-plasma, homocysteine remains stable for up to four days at room temperature. The most important indications for analysing homocysteine are deficiency of vitamin B12 or folate, premature cardiovascular disease and inherited homocystinuria. The clinical usefulness of the assay is based on the fact that the intracellular metabolism of homocysteine is dependent on vitamin B12, folate and vitamin B6. Moreover, homocysteine may be an atherogenic agent, and there is increasing evidence that a high level of homocysteine in plasma is an independent risk factor for developing premature atherosclerotic disease. PMID- 1412349 TI - [Highly specialized medicine. How to assign the tasks?]. AB - Norway has four million inhabitants and five university hospitals, each serving one health region. The authors describe the work of a governmental medical committee, whose mandate is to advise on where to locate the various highly specialized medical services. Important questions have been the relationship between experience and quality, and the desire of each university clinic to be able to provide treatment within its own region for most health problems. Their reasons are concern about research and specialist training, and the preference of patients for treatment near to home. A list of proposed national and over regional centers for certain treatments has been prepared on the basis of the experts' report and comments from all university clinics. These recommendations have provided a medical basis for later economic and political analyses prior to final decision by the Government. Norwegian legislation permits strong governmental regulation of the highly specialized health services. PMID- 1412350 TI - [Treatment of hypertension in the elderly--diuretics/atenolol?]. PMID- 1412351 TI - [Treatment of heart failure]. PMID- 1412352 TI - [Radiation accidents]. PMID- 1412353 TI - [The role and qualification of the teacher in changing medical education]. PMID- 1412354 TI - [How are you? On use of self-reported health status in medical research]. PMID- 1412355 TI - [Mucosal lesions in the pars esophagus in swine: prevalence and the effect of stress]. AB - Morphological investigations of slaughterhouse material revealed a prevalence of 63% of the sows (n = 224) and 36% of the slaughter pigs (n = 209) with mucosal lesions in the pars oesophagea. The mucosal lesions were composed of severe hyperkeratosis, erosions or ulceration. Microscopic examination showed that hyperkeratosis is attended with parakeratosis. From experiments in a climate controlled pighouse it could be concluded that mixing of unfamiliar pigs resulted in higher prevalences of gastric lesions as compared with keeping the litter together until the end of the experiment (farrow to finish system). There was no relation between gastric lesions and climatic stressors or between gastric lesions and growth and sex of the pigs. When pigs, according to social ranking, were divided in high, middle and low rank it showed that more pigs in the middle ranked group had gastric lesions. The serum pepsinogen was not related with gastric lesions. There was a tendency that plasma cortisol increased with severity of gastric lesions. There was a strong significant 'litter-effect', which can indicate a genetic predisposition for the development of gastric lesions. Maybe that the presence of mucosal lesions in the pars oesophagea can be used as an objective indicator for welfare in intensive pig husbandry. PMID- 1412356 TI - [2 cases of 'hardware' foreign objects in ponies]. AB - An obstruction of the small intestine was suspected in two ponies with colic. At surgery and at necropsy, the cause of the colic appeared to be an inflammation process caused by perforation of the jejunum by a piece of wire. One pony recovered after laparotomy and enterectomy, but had to be put down eight weeks later because of severe laminitis. The other pony was euthanized immediately after clinical evaluation. PMID- 1412358 TI - [Application of lungworm vaccination in severe lungworm disease]. PMID- 1412357 TI - [Feces in calves]. PMID- 1412359 TI - [How often does urinary incontinence occur as a complication following ovario hysterectomy in dogs?]. PMID- 1412360 TI - [Be wise--refer! Fact or fantasy?]. AB - On the occasion of his retirement as an active specialist in Surgery dr. P.H.A. Poll describes the history of the development of the specialties in Veterinary Medicine in The Netherlands and carefully looks forward. As a tribute, his specialist colleagues, all related to the Companion Animal Hospital "De Wagenrenk", publish one or more case reports from there respective disciplines (ophthalmology, surgery, radiology, dermatology). PMID- 1412362 TI - [Conjunctivitis in rabbits]. PMID- 1412361 TI - [Possible significance of spiral-shaped bacteria in the etiology of abomasal ulcers in adult cattle]. AB - Enzyme-chemical and histological evaluations were used to examine the abomasal mucosa of adult cattle with or without mucosal lesions of the corpus. Urease activity was detected with the CLO (Campylobacter-like organisms) test in the abomasal mucosa of all cattle except one, which had mucosal lesions. Spiral shaped bacteria were visualised histologically in the mucus layer, with the highest number being found in the pars pylorica. Variable amounts of intra epithelial mucin were found in the corpus and pars pylorica of both test and control cattle. Most inflammatory cells were found in the lamina propria of the pars pylorica. It is suggested that spiral-shaped bacteria, together with a diminished mucosal barrier, play a role in the pathogenesis of abomasal ulcers in adult cattle. PMID- 1412363 TI - [Acute soporous calf]. PMID- 1412365 TI - [Diseases in bees in The Netherlands]. PMID- 1412366 TI - [Environmental pollution and attendant contamination of agricultural domestic animals. Practical conditions in the provinces]. AB - Cattle are exposed to pollution by air, water, grass or soil. Exposure to environmental pollution is mainly through the eating of contaminated grass or feed. Case studies in the province of South-Holland show the importance of risk evaluation not just for human health but also for the health of cattle. The sequence "environment-cattle-public health" needs attention. The economic effects of pollution on agriculture may be considerable. PMID- 1412364 TI - [Inspection and re-inspection]. PMID- 1412367 TI - [Plants as transfer factor of environmental pollutants to domestic animals]. AB - Environmental contaminants in pasture and fodder crops may be 'carried over' to animal products and thus contribute to the contaminant burden of man. The processes by which plants collect contaminants from their environment can be divided into three categories: interception (mainly atmospheric deposition), surface contamination from adhering soil, and uptake from the soil (either by roots or by leaves after volatilization). In the field all processes may operate at the same time, but one is them often predominates. Identification of the (most) relevant process is a prerequisite for effective measures to reduce the burden of contaminants in plants and animals as well as man. PMID- 1412368 TI - [Behavior of environmental contaminants in farm livestock]. AB - Knowledge about pharmacokinetic factors is essential to evaluate the consequences of the exposure of farm animals to high levels of environmental contaminants. The bioavailability, which depends on for instance the exposure route and the matrix in which the contaminant is embedded, is of primary importance. The exposure of an animal expressed as internal dose rate is determined by the efficiency of the various elimination processes. If the combined rate of these processes is low, high body concentrations relative to exposure rate will occur. Metabolic elimination may lead to the formation of toxic metabolites and in that case it is necessary to study these metabolites as well. Residue problems may occur as a consequence of substance properties and/or the presence of specific binding proteins in organs and tissues. Finally, pharmacokinetic studies should be conducted at various levels of exposure as some kinetic processes may be non linear in nature. PMID- 1412369 TI - [Cortical necrosis]. PMID- 1412370 TI - [Toxicity of cadmium in cattle]. AB - After having investigated the metabolism of cadmium in plants and animals, the Animal Health Service of North Brabant in 1982 instigated research into the level of cadmium in the livers and kidneys of beef cattle kept in the vicinity of a zinc processing factory. Cadmium levels in these cattle were more than twice as high as those of cattle kept in control areas. Clinical abnormalities as a result of the increased cadmium levels were not observed, although haemoglobin and iron levels, iron-binding capacity and iron saturation were lower in these animals than in control animals. Cadmium therefore appears to have an adverse effect on iron absorption. Administration of high doses of cadmium for a limited period to 14 heifers did not cause discernable clinical abnormalities. These animals retained cadmium to a much smaller extent than anticipated on the basis of data for monogastric (mainly rats) animals. PMID- 1412372 TI - [Contamination of production animals with environmental pollutants and public health risk]. AB - Exposure to dairy products contaminated as a result of environmental pollution can be an important route of exposure for humans. Whether this route of exposure will cause a serious health risk depends on many factors. In this paper three examples of different types of environmental pollution are discussed with regard to exposure to contaminated dairy products. Specific groups in the Dutch population could be at risk, because the "silent" chronic contamination of dairy products. Human risk assessment, on which many standards for tolerable levels of contaminants in food are based, should take into account not only exposure of the average human, but also the more than average exposure of specific groups at risk. PMID- 1412371 TI - [Food products of animal origin and environment contaminants]. AB - Environmental contaminants may reach humans via products of animal origin is obtained mainly from production animals but also from fish. Heavy metals such as lead, mercury and cadmium are present in food in minor quantities only and, in general, do not represent a serious threat to the consumer. Xenobiotics which accumulate in adipose tissue are discussed subsequently. In The Netherlands, the presence of organochlorine pesticides is not problematic anymore. HCH isomers, however, still require attention. The same applies for PCB's and dioxins in fish and in milk, respectively. Finally, some attention is paid to the way in which food of animal origin can become contaminated by certain radionuclides. PMID- 1412373 TI - [Dacryocystitis]. PMID- 1412374 TI - [Veterinary dentistry (6). From back to the roots to buck on the rock]. AB - The Royal Netherlands Veterinary Association is organizing its yearly congress in the old city of Utrecht where all Dutch veterinarians have been graduated. 'Back to the roots' is the slogan of this meeting. The Diergeneeskundige Studenten Kring (the Dutch veterinary students association) is celebrating the 60th anniversary at the same time with the slogan: 'Bok on the rock.' On the first day of this celebration the students are organizing a symposium Veterinary Dentistry. The author has been inspired by the two slogans to a discourse in which the past and the future of animal dentistry is discussed. In 'Back to the Roots' history and anecdotes about dental treatments are presented. It is clear that dental treatment in animals is possible for every well-educated veterinarian. In 'De bok on the rock' the author shows the ropes how to develop a dental minded practice. Oral examination, a good knowledge of dentistry and a dental-minded staff are the most important factors to build up such a practice. There is an abundance of dental patients in every practice. An optimal client education and coaching is the best way to find them and to follow them. PMID- 1412375 TI - Intravascular membrane oxygenation and carbon dioxide removal--a new application for permissive hypercapnia? AB - Pressure limited ventilation or "lung rest" may prevent further exacerbation of acute lung injury from high airway pressures. A therapeutic goal of an intracorporeal oxygenation and carbon dioxide removal device (IVOX) is reduction of airway pressures. We noted increased IVOX CO2 removal as mixed venous CO2 increased in experimental animals. However, we recognize the limited clinical utility of removing approximately 30% of venous CO2. Therefore, intentional hypoventilation to limit airway pressures (mild permissive hypercapnia) was used in 5 patients with respiratory failure, and again we noted improved CO2 removal with increasing mixed venous CO2 concentrations. Preliminary calculations demonstrate that a CO2 gradient of approximately 70 mm Hg is needed to remove 100 ml CO2/min. The use of more aggressive permissive hypercapnia protocols with IVOX may permit further reduction in airway pressure without problems of severe respiratory acidosis. PMID- 1412376 TI - Temporary lung support using an intravascular gas exchanger. AB - Severe respiratory failure may be difficult to overcome by conventional mechanical ventilation. As an alternative to the very demanding lung support using various modalities of extracorporeal circulation (ECMO, ECLA, etc.) we evaluated an intravascular gas exchanger (IVOX) in a "reversible" bovine model. Several degrees of hypoventilation were studied with and without intravascular gas exchange in 5 endotracheal intubated, anaesthetized, and volume-controlled ventilated animals (body weight 73 +/- 4 kg). After systematical heparinization (300 IU/kg body weight) the animals were instrumented with EKG electrodes, thermodilution pulmonary artery catheter with continuous measurement of O2 saturation, central venous and femoral arterial catheter, etc. The intravascular gas exchanger made from siliconized microporous polypropylene hollow fibres was placed in the caval veins under radiofluoroscopic control. The following scenarios were studied without and with intravascular gas exchange (gas inlet 100% O2): Normoventilation (with 14-20 strokes/min) at F10(2) 0.50 and at F10(2) 0.21; Hypoventilation (ventilator frequency reduced to 50% and tidal volume reduced to 50% of normoventilation) at F10(2) 0.50 and at F10(2) 0.21. Hemodynamics, mixed venous O2-saturation, arterial and venous blood gases, and gas-exchanger exhaust were analyzed after stabilization over 15 minutes (mean +/- standard deviation). Blood gas analyses showed significant improvement with intravascular gas exchange during hypoventilation at F10(2) 0.21: pH moved from 7.10 +/- 0.17 to 7.19 +/- 0.15*, PaCO2 moved from 9.9 +/- 4.2 kPa to 8.7 +/- 2.8*, PaO2 moved from 6.5 +/- 1.2 kPa to 7.3 +/- 0.8* and mixed venous O2 saturation moved from 33.9 +/- 16.0% to 48.1 +/- 4.6* (* = p less than 0.05 for without versus with intravascular gas exchange).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412377 TI - The influence of obesity on perioperative morbidity: retrospective study of 502 aortocoronary bypass operations. AB - The incidence of perioperative complications after coronary artery surgery was investigated by a retrospective study of all 502 patients undergoing coronary artery bypass graft (CABG) surgery in our Department between January 1st and December 31st of last year (1990). Furthermore, the influence of obesity on the early results of surgery was assessed and the effect of preoperative weight reduction on perioperative complication rates examined. Obese patients had a greater incidence of left-stem coronary artery stenosis (p less than 0.001), hyperlipidaemia (p less than 0.05), hypertension (p less than 0.05), diabetes mellitus (p less than 0.02), and were in general younger at the time of operation (57.9 +/- 8.4 vs. 60.8 +/- 8.5 years). There were no differences in the surgery performed and in operative mortality, but there were some in perioperative morbidity. Obese patients had higher rates of infection (p less than 0.02), sternal dehiscence (p less than 0.02), arrhythmias (p less than 0.02) and myocardial infarction (p less than 0.02). No significant differences were identified in obese patients with or without preoperative weight reduction, although there was a trend of better postoperative recovery and results in patients having undergone preoperative weight reduction. Analysis of our results demonstrated obesity to be an independent risk factor for perioperative complications, hospital morbidity, and length of hospitalization. PMID- 1412378 TI - Pulmonary atresia with intact ventricular septum: results and predictive factors of surgical treatment. AB - Between 1970 and 1989 26 children were operated for pulmonary atresia with intact ventricular septum (PA/IVS). According to the degree of right heart hypoplasia the patients were divided into 3 groups of mild (5), moderate (17) or severe (4) hypoplasia. Palliative operations were performed in 25 children (17 male, 8 female) at a mean age of 10 days: 13 valvotomies (valv.), 5 aortopulmonary shunts, and 7 valv. plus shunt. One patient had total correction as primary procedure. A total of 17 reoperations was necessary in 12 of 26 patients (10 palliations, 7 total corrections). Total corrections were: 2 conduits and 5 patches of the right-ventricular outflow tract (RVOT). Total mortality was 14/26 (54%) children (early 10/26 = 38%, late 4/26 = 16%). After total correction mortality was 3/7 (43%) patients. After a mean follow up of 10.8 years after palliation the 12 survivors are mostly in NYHA class I. Actuarial survival after palliation was 60% after 30 days and 44% after 5 and 10 years. We analyzed 9 clinical and hemodynamic variables by univariate and multivariate analysis to assess the predictive factors of postoperative outcome. Multivariate analysis disclosed the degree of right-ventricular hypoplasia (p = 0.023) as an independent predictor for death whereas the age at palliation only approached significance (p = 0.065). We recommend the following surgical strategy, aiming in the first place at decompressing the right ventricle: in mild hypoplasia valvotomy alone or combined with a shunt for palliation, in moderate hypoplasia shunt plus patch of the RVOT and in severe hypoplasia shunting alone. In case of a restrictive foramen ovale initial balloon septostomy is performed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412379 TI - Cardiodynamic effects of dopamine and dobutamine. AB - On 11 patients undergoing coronary surgery, at the end of the surgical intervention, the inotropic responses to 0.4 and 0.8 microgram x kg-1 x min-1 dopamine and dobutamine given via the aorto-coronary bypass directly into the coronary artery were compared. These dosages correspond to ones 10 times greater applied intravenously. The measurements were made using needle force probes which were implanted into the myocardial offstream area in the left ventricular wall. Bypass flow was measured simultaneously by an electromagnetic flow probe. There is a significant increase in coronary bypass flow induced by both rates of 0.4 and 0.8 microgram x kg-1 x min-1 dobutamine, but there was no significant effect on bypass flow induced by dopamine. Developed myocardial force is raised more by dobutamine medication than by dopamine. However, the rate of contraction increases significantly and relaxation is significantly accelerated by dopamine at both dosages. A significant increase in rate of contraction and relaxation was only induced by the higher dosage of 0.8 microgram x kg-1 x min-1 dobutamine. PMID- 1412380 TI - The effect of superoxide dismutase and reduced glutathione on cardiac performance after coronary occlusion and reperfusion--an experimental study in dogs. AB - To determine the effect of Superoxide Dismutase (SOD) and Reduced Glutathione (GSH) as free-radical scavengers on cardiac performance in the reperfusion period up to 60 minutes after occlusion of the Left Anterior Descending artery (LAD), 16 dogs were selected for study. In the 30th and 60th minutes of LAD occlusion and reperfusion periods Cardiac Output (CO), Heart Rate (HR), Mean Arterial Pressure (MAP), Pulmonary Capillary Wedge Pressure (PCWP), Coronary Perfusion Pressure (CPP), Rate Pressure Product (RPP) and Triple Index (TI) values were determined. Of the 16 dogs, 7 as controls and 7 treated with SOD and GSH could be included in the study, and 2 had to be excluded because of death. In the 30th and 60th minutes of reperfusion period, the treated dogs had higher CO and CPP (p less than 0.05, p less than 0.01 respectively), MAP values were different (p greater than 0.05, p less than 0.05 respectively) from controls, whereas lower HR (p less than 0.05, p greater than 0.05, respectively), RPP and TI values (p less than 0.05) were determined. It was concluded that the combination of SOD and GSH may improve cardiac performance in the reperfusion period. PMID- 1412381 TI - Oxygen free radical scavengers and reperfusion injury in dog lung preserved in cold ischemia. AB - Oxygen-derived free radicals are now considered important contributors to tissue injury associated with ischemia and reperfusion. The purpose of this study was to determine the influence of oxygen free radical scavengers on reperfusion injury. The left lower lobes of 15 canine lungs were isolated, preserved, and then reperfused for 120 minutes. Three groups of lobes were studied: Group 1 (n = 5), without ischemia, group 2 (n = 5) four hours of cold ischemia in Euro-Collins solution, group 3 (n = 5) four hours cold ischemia+oxygen free radical scavenger glutathione (0.1 nmol/L) given at the moment of perfusion. Extravascular lung water (grams per gram of blood-free dry lobe weight) after reperfusion was 2.82 +/- 0.32, 5.06 +/- 0.45, 4.21 +/- 0.33 for groups 1 through 3 respectively (p less than 0.001 group 1 versus group 2, p less than 0.001 group 2 versus group 3). Lung tissue lipid peroxidation, measured as thiobarbituric acid reactive material was 125 +/- 11, 270 +/- 30, and 185 +/- 17 nmol/g dry lobe weight for groups 1, 2 and 3 respectively (p less than 0.05 group 2 versus 1 and group 3 versus group 2). The data suggest that oxygen free radical scavengers attenuate reperfusion injury. PMID- 1412382 TI - Added hospital stay due to wound infections following cardiac surgery. AB - To determine the prolongation of hospital stay due to postoperative wound infections following cardiac surgery, a prospective cohort study was performed by matching multiple control patients without infection to each infected patient (= case). Out of 22 cases, no patient died. No case had to be excluded from the matching process because of a lack of suitable control patients. The maximum number of controls per case was 10. The mean added stay was 12.2 days constituting a considerable prolongation of stay due to wound infection in cardiac surgery. PMID- 1412383 TI - Aortoiliac endarterectomy: a 9-year experience. AB - Thirty-two patients (median age: 51 years) underwent aortoiliac endarterectomy between 1982 and 1990, for disabling claudication (27), rest pain (3), and tissue loss (2). There was no post-operative death and morbidity affected 6 patients. Five patients showed insufficient or suboptimal vascularisation of a limb which justified early reoperation in four. Follow-up was obtained in 31 patients with a median time of 36 months (6 months to 8 years). Five patients experienced recurrence of claudication symptoms: two received an aortofemoral bypass at 6 and 36 months. In the other patients, distal arterial occlusive disease accounted for recurrence alone (2 patients) or in association with aortoiliac involvement (1). Technical problems or disputable indications were responsible for postoperative failure in 3 cases or early recurrence of symptoms in 2. Cumulative patency rates of aortoiliac endarterectomy were 94 and 90 per cent at 2 and 5 years, and actuarial rates of clinical improvement were 90 and 82 per cent at 2 and 5 years, respectively. Aortoiliac endarterectomy provides the advantages of avoiding foreign material. The success of this reconstruction depends on strict criteria of selection and surgical expertise. It is indicated for the relatively young patient with nonectasic disease where atherosclerosis has not attacked the external iliac arteries. PMID- 1412384 TI - Congenital absence of the left pericardium in combination with left pulmonary artery hypoplasia, right aortic arch, and secundum atrial septal defect. AB - The authors describe a rare congenital anomaly--absence of the left pericardium- in one patient who was operated on for a secundum atrial septal defect. The symptomatology, diagnostic, and therapeutic possibilities are discussed. PMID- 1412385 TI - Modified Janke net technique for exposure of the circumflex artery. AB - A novel method of the circumflex coronary artery exposure by rotating the heart, using a Janke net and a silicone rubber tube, is described. PMID- 1412386 TI - Surgical treatment of solitary peripheral pulmonary artery aneurysm associated with ventricular septal defect. AB - In the case presented a solitary peripheral pulmonary artery aneurysm occurred in a woman with ventricular septal defect (VSD). During the operation of repairing the VSD under cardiopulmonary bypass, the pulmonary artery aneurysm (PAA) suddenly ruptured into the bronchus and a large amount of air entered the pulmonary artery and right ventricle when the anesthetist inflated the lungs. The air in the right ventricle could not be evacuated completely, so we had to remove the lobe where the aneurysm was located. The operation was successful and the postoperative course was uncomplicated. PMID- 1412387 TI - Cardiac surgery in Germany during 1991. A report by the German Society for Thoracic and Cardiovascular Surgery. PMID- 1412388 TI - Surgical critical care: who is responsible? PMID- 1412389 TI - Laser Doppler velocimetry measurement of canine mucosal circulation response to bronchial artery reperfusion after lung transplantation. AB - Left lung transplantation accompanied by reestablishment of the circulation of the bronchial arteries by simultaneous transplantation of part of the aorta was performed on seven dogs. Mucosal circulation of the bronchi at the anastomosis was evaluated using laser Doppler velocimetry (LDV). Since the donor lung must maintain blood supply through the bronchial arteries, the donor aorta from its ascending portion to the descending portion below the outlet for the last bronchial artery was retained with the lung graft. The distal end of the left brachiocephalic artery was sutured to the side of the recipient aorta when the blood supply to the bronchial arteries was to be restored. The LDV values before reperfusion of the bronchial arteries were 20 to 65% (mean: 42.8%) of the preoperative value. Since the LDV values increased to 36 to 125% (mean: 79.9%) of the control, blood flow to the bronchial mucosa increased evidently. Four out of seven dogs died one to two days after the operation due to bleeding and operative stress. One dog was sacrificed on the 4th postoperative day and another on the 16th. The last dog died 40 days after surgery. The unfavorable course of the LDV values in these three dogs suggest that the method used does not ensure an adequate blood supply to the bronchial arteries in the long term. PMID- 1412390 TI - Thoracoscopic resection of a pericardial cyst. AB - The development of new instruments that can be applied endoscopically opens up new possibilities for minimally invasive thoracic surgery. The surgical technique is exemplified by a thoracoscopic resection of a pericardial cyst. The benefits for the patient are impressive: minimization of surgical trauma and postoperative pain, a short convalescence, and an optimal cosmetic outcome. PMID- 1412391 TI - Thoracoscopic resection of benign schwannoma. AB - The recent improvement of endoscopic surgical instruments allows new therapeutical application of thoracoscopy. We report a thoracoscopic resection of a benign schwannoma of the 6th intercostal nerve in a 35-year-old patient. The operative technique and extraction of the tumor from the chest is described. Postoperative morbidity was minor. We consider the thoracoscopic resection as first choice of treatment. PMID- 1412392 TI - Diaphragmatic cyst with elevated level of serum tissue polypeptide antigen. AB - A 58-year-old woman with a mesothelial cyst of the diaphragm showed high level of serum Tissue Polypeptide Antigen (TPA) and cyst fluid TPA. Mesothelial cells of the cyst may excrete TPA and TPA was accumulated in the cysts. The measurement of tumor marker such as TPA of the serum or of the content of the cyst is useful in observation of the clinical course. PMID- 1412393 TI - Madura foot of the chest wall; cure after radical excision. AB - Maduromycosis is a chronic granulomatous condition caused by fungal infection and is rarely encountered in Europe. To our knowledge, this is the first report of a case of maduromycosis affecting the chest wall in the United Kingdom. Conservative excision and drainage of the lesion combined with ketoconazole treatment in a dose 400 mg daily for several months failed to cure the condition. However, radical excision of the lesion combined with myoplastic repair of the defect in the chest wall eradicated the disease. Maduromycosis can occur in the chest wall and should be suspected in the immigrant population from tropical and subtropical areas. We recommend radical resection of similar lesions, combined with prolonged treatment with an antifungal agent e.g. ketoconazole when the causative organism is madurella mycetomis. PMID- 1412394 TI - Primary rhabdomyosarcoma of the diaphragm. Report of a case presenting with hemothorax. AB - A rare case of embryonal rhabdomyosarcoma of the diaphragm occurring in an adult male and presenting with hemothorax is reported. The unusual clinical features of this patient underline the need for an accurate preoperative evaluation. The surgical procedure consisted of left thoracotomy with resection of the neoplasm, including a portion of the diaphragm muscle, and then reconstruction. One month after discharge chemo- and radiotherapy were carried out. The immunohistochemical study proved to be very helpful for the pathological diagnosis. A three years follow-up with patient alive and disease-free confirms that a multimodal approach may prove effective in the long term. PMID- 1412395 TI - The optimal temperature for 24-hour heart preservation using continuous coronary perfusion method. AB - This experiment was designed to compare three preservation temperatures, 0 degrees C, 4 degrees C, and 10 degrees C, in 24-hour heart preservation using a continuous coronary perfusion method in terms of myocardial extracted enzymes during preservation (CPK, LDH, and GOT), left ventricular (LV) function at reperfusion and ultrastructural changes both at the end of preservation and at reperfusion. Rabbit hearts were preserved at 0 degrees C (n = 6), 4 degrees C (n = 6), and 10 degrees C (n = 6) for 24 hours and reperfused with arterial blood from the abdominal aorta of support rabbits. The value of CPK in the 10 degrees C group was statistically higher than those of the 0 degrees C group or 4 degrees C group (p less than 0.05: 0 degrees C vs 10 degrees C, p less than 0.025: 4 degrees C vs 10 degrees C). Left ventricular developed pressures (LVDPs) at 60 minutes after reperfusion in the 4 degrees C group were statistically greater than those in the 0 degrees C group and 10 degrees C group at several LV balloon volumes (p less than 0.005: 4 degrees C vs 0 degrees C or 10 degrees C). Electron microscopic examination at reperfusion demonstrated remarkably swollen mitochondria associated with disruption of cristae in the 0 degrees C and 10 degrees C groups, but much less morphological change in the 4 degrees C group throughout preservation and reperfusion. From an overall view point of these enzymatic, functional and ultrastructural results, 4 degrees C proved to be a superior preservation temperature of choice for prolonged heart preservation. PMID- 1412396 TI - Retrograde coronary sinus cardioplegia in myocardial revascularization: hemodynamic evaluation of the influence on the right-ventricular function. AB - The problem of the efficacy of right-ventricular protection with retrograde coronary sinus cardioplegia is studied. Sixty patients undergoing myocardial revascularization were prospectively assigned to receive cold St. Thomas' Hospital cardioplegia into the aortic root (30 patients) or retrogradely in the coronary sinus (30 patients). The two groups were similar concerning preoperative and operative data. The hemodynamic recovery postoperatively was good in both groups, the increase of the heart rate, the decrease of the mean aortic pressure and the right-ventricular stroke-work index were not significantly different in the two groups. However, right atrial pressure increased significantly (p less than 0.001) in patients who received cardioplegia anterogradely and decreased, but not significantly, in the retrograde group. The data suggest that the decrease of the right-ventricular stroke-work index in the anterograde group is related to a depressed contractility and in the group with retrograde delivery of cardioplegia to a decreased preload. There were no differences between the groups with respect to clinical outcome. We conclude that retrograde delivery of cardioplegia results in an excellent protection of the right-ventricular function in elective myocardial revascularization. PMID- 1412397 TI - Pediatric myocardial protection in the United States: a survey of current clinical practice. AB - A nationwide survey of institutions in the United States that perform congenital heart disease surgery was conducted to obtain an overview of the current use of myocardial protection in pediatric patients (aged 0-16 years). One hundred and one (55%) of 183 institutions responded, completing a 4-page questionnaire about pediatric cases in 1989. A total of 12,072 cases were represented. Caseloads ranged from 7 to 498 at these institutions (mean 124, median 30). Cardioplegia was used by 100 institutions (44 blood, 45 crystalloid, 11 both). Administration was guided by formulas alone in 69 and by clinical criteria alone in 32. A wide variety of compositions of cardioplegic solutions was found with no preference for any particular type. No correlation between caseloads and cardioplegic solutions was found. Hypothermia was used by all institutions, with a mean of 25.8 +/- 3.5 degrees C for a simple ventricular septal defect closure. Deep hypothermia and circulatory arrest were used in 3048 cases (25.2%). A clear trend indicated that circulatory arrest was used more frequently in larger institutions (p less than 0.0001). Fibrillation as a strategy was used in 45 institutions. Twenty-five institutions changed cardioplegia technique during 1989. The findings suggest that, even though no consensus exists about its ideal composition, cardioplegia in conjunction with hypothermia is currently the strategy most often used for pediatric myocardial protection. PMID- 1412398 TI - Successful resection of a distal aortic arch aneurysm in a patient with Behcet's disease using an "aortic no-touch" technique and hypothermic total-body retrograde perfusion. AB - Resection of a false aneurysm of the aortic arch in a patient with Behcet's disease was safely performed using an "aortic no-touch" technique. This consisted of: (1) femoral artery and bicaval cannulation, (2) profound hypothermia (below 20 degrees C) by core cooling, (3) retrograde cardioplegia through the coronary sinus, and (4) total body retrograde perfusion via both venae cavae without aortic cross-clamping. The patient showed no evidence of neurological damage and the postoperative course was uneventful. PMID- 1412399 TI - Aortic annular enlargement with the use of a homograft valve. AB - A technique of annular enlargement for use in homograft aortic valve surgery is described. Potential advantages of this technique, that allows convenient valve sizes in small aortic annuli, lie in the pediatric group of patients requiring aortic valve replacement. PMID- 1412400 TI - Congenital quadricuspid aortic valve associated with aortic regurgitation. AB - A case of quadricuspid aortic valve is described. The aortic valve consisted of 3 equal-sized and 1 smaller cusps, and a supernumerary cusp located between the right and noncoronary cusps. A right coronary ostium was close to the accessory commissure, and in a lower position. Three fenestrations were found at the supernumerary commissure. Aortic valve replacement was performed successfully with a St. Jude Medical prosthetic valve. On histological examination, the resected cusps showed fibrotic thickening with calcification and no sign of previous inflammatory disease. Quadricuspid aortic valve must be considered a malformation capable of leading to severe valve failure in later life. PMID- 1412402 TI - Intracardiac needle in a man with self-injurious behaviour presenting with only a heart murmur. AB - Symptoms of a heart murmur in a 48-year-old male schizophrenic patient with self injurious behaviour were investigated. Immediately noticeable were multiple scars on his hands. Clinical evidence of subcutaneous needles and aortic regurgitation was found. Echocardiography revealed a linear metallic foreign body across the interventricular septum. He underwent surgery and via a right atriotomy, a needle from the same location was removed. PMID- 1412401 TI - Intracardiac primary fibrosarcoma. Case report and literature review. AB - A 58-year-old woman was hospitalized because of shortness of breath, cough, weakness, and physical signs suggestive of mitral stenosis. Echo-Doppler examination revealed a left atrial mass. This was removed and turned out to be a fibrosarcoma. Recurrence of the tumor with metastases into the pericardium, thyroid goiter, and left kidney led to the patient's death 6 months later. The clinical and pathological features of our rare case are compared with those in the literature. PMID- 1412403 TI - [Situation of heart surgery in Germany 1991]. PMID- 1412404 TI - [Stridor in infants: sometimes not so innocent]. AB - Stridor is a frequent symptom in the neonate. Often it consists of a discrete inspiratory stridor in an alert child or of a transient symptom of a viral respiratory infection. In both cases no specific therapy is required. Whenever stridor occurs in the first months of life, or when it is severe or chronic, or when stridor also persists throughout expiration, an underlying anatomic anomaly frequently exists. The following steps are important to the diagnostic management: besides a detailed and complete history and physical examination, an X-ray of the airways and, if necessary, laryngo/bronchoscopy, angio(cardio)graphy or computerized tomography of the chest and the cervical region. Subsequently, appropriate therapeutic management can be initiated by proficient and accomplished physicians. PMID- 1412405 TI - [Chronically tired or the chronic fatigue syndrome in an adolescent]. AB - To fulfill the criteria of the chronic fatigue syndrome a patient must have new onset persistent or relapsing, debilitating fatigue or easy fatigability. The symptoms do not resolve with bedrest and are severe enough to reduce or impair average daily activity below 50% of the patient's premorbid activity level for a period of at least 6 months. Other clinical conditions that may produce similar symptoms must be excluded. Using a case history the (differential) diagnosis, treatment and prognosis of the chronic fatigue syndrome are discussed. PMID- 1412406 TI - [Complete situs inversus in one half of a monozygotic twin]. AB - The history of a monochorial monoamniotic twin, born at 27 weeks of gestation, in which a situs inversus was present in one of the twin is given. The incidence of a situs inversus in twins and the etiologic factors as described in literature are given. PMID- 1412407 TI - [Vertebral osteomyelitis in an infant]. AB - Neonatal osteomyelitis is uncommon. The disease starts often without signs of infection and may lead to severe complications. A case is reported of a neonate with vertebral osteomyelitis of the cervical vertebrae. Difficulties of diagnosing the disease and several therapeutic regimes proposed in the literature are discussed. PMID- 1412408 TI - [Ureterocele in children]. AB - Two case reports of children with ectopic ureteroceles are presented. The embryologic development, symptoms, diagnosis and treatment are discussed. Hemi nephroureterectomy is the treatment of choice. In instances, such as serious urinary tract infections, massive vesicoureteral reflux in other ureters and in single system ureteroceles, endoscopic incision of the ureterocele can be effective in terms of control of infection and decompression of other kidney parts. Definite surgery can be deferred until the child is in a better condition. PMID- 1412409 TI - [Lithium poisoning in a newborn infant]. AB - We describe a newborn with a lithium intoxication. Her mother used lithium during her entire pregnancy. The intoxication was successfully treated with an exchange transfusion. PMID- 1412410 TI - Idiopathic dilated cardiomyopathy: lack of association between circulating organ specific cardiac antibodies and HLA-DR antigens. AB - Organ-specific cardiac antibodies are serological markers of autoimmunity in dilated cardiomyopathy (DCM). HLA-DR4 and possibly DR5 are immunogenetic markers of susceptibility in DCM, but it is not known whether they are associated with autoantibody production. We studied the frequency of HLA-DR antigens and the presence of organ-specific cardiac antibodies in 80 DCM Caucasian patients from Northern Italy. HLA-DR typing was performed by serology; 289 healthy blood donors from the same region were tested as controls. HLA-DR frequencies in DCM were also compared with VIII International Workshop control data for Italy. Cardiac antibodies were detected by indirect immunofluorescence on human heart. Skeletal muscle was used to identify cross-reacting antibodies. The prevalence of cardiac antibodies in DCM was: organ-specific 34% and skeletal muscle cross-reactive 30%. The previously reported positive association between DCM and HLA-DR4 was confirmed using either the controls from the same region (21.25% vs 10.73% p = 0.02, relative risk = 2.30) or from all of Italy (21.25% vs 12.3%, p = 0.03). HLA DR5 frequency was slightly but not significantly higher in DCM than in controls from the same region (46.25% vs 31.49% p = 0.02, relative risk of 1.87, p corrected = NS) or from all of Italy (46.25% vs 35.8% p = NS). HLA-DR3 frequency was lower in DCM than in controls from the same region (12.50% vs 29.41% p = 0.003, relative risk of 0.36, p corrected = 0.03). This negative association was not confirmed using the control data from the whole of Italy (12.50% vs 16.5% p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412411 TI - The HLA DQB1*0502 allele is neutrally associated with insulin-dependent diabetes mellitus in the Sardinian population. AB - In the Sardinian population a very high incidence of insulin-dependent diabetes mellitus (IDDM) and the lack of HLA-DR2 protective effect due to the high frequency of the A2, Cw7, B17, 3F31, DR2, DQw1 extended haplotype has been reported. This haplotype, carrying a Serine at position 57 of the DQB1*0502 allele, has been previously reported to be underrepresented in patients when compared to controls. In order to provide an explanation for this finding, we defined by RFLP analysis the HLA haplotype of 45 Sardinian IDDM patients and 49 controls. All DR-2DQw1 subjects were molecularly characterized at the HLA DQA and DQB loci. All DR2-positive patients and the vast majority of the DR2-positive controls had the DQB1*0502 allele at the DR2-linked DQB1 locus, with no statistically significant difference between the two groups. All DQA1 genes were the ones expected, with only two exceptions. Nine out of 10 of the DR2-positive patients were compound heterozygotes for DQB1*0201/DQB1*0502 alleles; only this allele combination was significantly increased (p less than 0.0003). Our data suggests that a) the DQB1*0502 allele is neutral for IDDM development and b) the susceptibility to IDDM in our DR2-positive patients is related to the compound heterozygous state between the neutral DQA1*0102/DQB1*0502 and the susceptibility DQA1*0501/DQB1*0201 alleles. PMID- 1412412 TI - Population and family studies of HLA-DR4 by use of oligonucleotide typing. AB - Using PCR and DR4 group-specific primers and SSO's we have examined DRB1*04 nucleotide polymorphisms in a population of 123 DR4-positive individuals (86 NAC, 27 Hispanics and 10 African Americans) from New York carrying a total of 134 DR4 haplotypes. We found that the distribution of DRB1*04 alleles on DR4 haplotypes differs in these three ethnic groups. In this relatively small population, certain alleles such as DRB1*0406 and 0411 were encountered only in Hispanics, while others such as DRB1*0403, 0408 and 0409 were found only in NAC (North American Caucasians). Such differences may be important in studies of HLA-DR4 and disease associations. Evidence from MLC and PLT studies of an HLA-B/DR crossover family, which was informative for the segregation of HLA-DRB1*0406 and DRB1*0407, supports the concept that subtypes of HLA-DR4 and/or associated HLA-DP alleles elicit T-cell alloreactivity, and may thus play a role in transplantation. PMID- 1412413 TI - HLA-DPB1*0401 is associated with the presence of autoantibodies reactive with the U1-70 kD polypeptide antigen of U1-small nuclear ribonucleoprotein among connective tissue disease patients. PMID- 1412414 TI - Dw14 is a Dw4-independent risk factor for rheumatoid arthritis among Norwegians. PMID- 1412415 TI - Molecular analysis of novel HLA-DR2.DQwl haplotypes in Asian Indians. PMID- 1412416 TI - A novel HLA-DPB1 sequence, DPB1*2301. PMID- 1412418 TI - HLA-DP polymorphism in Sudanese controls and patients with insulin-dependent diabetes mellitus. AB - Human leukocyte antigen (HLA) genes are candidates for susceptibility to insulin dependent diabetes mellitus (IDDM). The association of IDDM with particular DR and DQ alleles has been reported in all populations studied, but its association with HLA-DP alleles has been controversial. To address this question we analyzed 19 DPB1 and 2 DPA1 alleles and their associations in well-characterized Sudanese (an admixture of Arab and Black) IDDM patients (n = 71) and ethnically matched controls (n = 86) using polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) typing. There were no significant differences between the patient and control groups in the DPB1 frequencies. DPB1*0201, *0401 and DPA1*01 were the most frequent alleles in both IDDM patients and control subjects. Significant positive and negative associations between DPB1 and DPA1 alleles were detected in both groups. A novel DPB1 allele included in DPB1*1701 was identified. PMID- 1412417 TI - HLA antigens in Tlingit Indians with rheumatoid arthritis. AB - HLA-DR4 has been described in association with rheumatoid arthritis (RA) in multiple populations. We have studied HLA antigens in Alaskan Tlingit Indians. HLA-DR4 was decreased in the RA group (n = 32) compared with controls (n = 62) (6% vs 21% p = 0.07). The predominant DR4 allele observed was DRB1*0403 (Dw13.1). The most striking observation in these studies was a marked predominance of the DRB1*1402 allele encoding Dw16 (DRw14). This allele was present in 91% of RA cases, but was also highly prevalent in controls (80%, OR = 2.4 p = 0.20). DRB1*1402 only was observed in 47% of cases and 31% of controls. The DRB3*0101 (DRw52), and the DQA*0501 and DQB*0301 alleles encoding a subset of DQw3 were associated with DRB1*1402 in cases and in controls. HLA-Bw62 was increased in RA cases (28%) compared with controls (8%) (OR = 4.5, p = 0.01, corrected p = ns). PMID- 1412419 TI - Two new HLA DRB1 alleles found in African Americans: implications for balancing selection at positions 57 and 86. AB - Two new DRB1 alleles have been identified (DRB1*0303 and DRB1*0805) in African Americans that differ from known DRB1 alleles only by a glycine to valine exchange at position 86. The novel DRB1*0303 allele, found in one individual, has the same DQA1*0401-DQB1*04 haplotype as DRB1*0302, suggesting that it may be a recent diversification of *0302. The novel DRB1*0805 allele, identified in 4 individuals, was found on two haplotypes, sharing a DQA1*0501-DQB1*0301 haplotype with DRB1*0804, and a DQA1*0102-DQB1*0602 haplotype found with DRB1*0801 in some African populations. DRB1*0805 differs from *0804 only at position 57 and differs from *0801 only at position 86. Assuming that DRB1*0801 and DRB1*0802 are ancestral, based on their distribution in various human populations, DRB1*0805 may have been generated twice by two independent mutations or gene conversion events at each of these positions. Alternatively, DRB1*0805 may have arisen from a single gene conversion event (or mutation) and recombined to generate multiple DR-DQ haplotypes. These findings increase the number of DRB1 allelic pairs that differ only at position 86 to 9, suggesting strong balancing selection at this position. A number of DRB1 alleles for DR8 and DR4 also differ only at position 57, a site previously postulated to be strongly influenced by balancing selection in DQB1 alleles by phylogenetic analysis. PMID- 1412420 TI - Monoclonal antibodies specific for canine CD4 and CD8 define functional T lymphocyte subsets and high-density expression of CD4 by canine neutrophils. AB - The characteristics of canine homologues of CD4 and CD8, defined by murine monoclonal antibodies CA13.1E4 (IgG1) and CA9.JD3 (IgG2a) respectively, are described. These antibodies identify mutually exclusive subpopulations of non-B lymphocytes in peripheral lymphoid organs and blood. However, in thymus the antibodies defined populations of double-positive, double-negative and single positive cells that showed a progressive maturation consistent with that described for CD4 and CD8 in other mammalian species. Furthermore, functional studies clearly associated cytotoxic effector cell function with the subpopulation reactive with CA9.JD3 (CD8). In contrast, proliferation stimulated by allogeneic cells and mitogens was more pronounced in the subpopulation reactive with CA13.1E4 (CD4). Cell and tissue distribution studies revealed that CA13.1E4 stained neutrophils with equivalent intensity to the staining of peripheral T cells. CA13.1E4 precipitated a 60 kD protein from the surface of T cells and highly purified neutrophils under both reducing and nonreducing conditions. CA9.JD3 precipitated a heterodimer of 32 kd and 36 kD under reducing conditions, and a 70 kD protein under non-reducing conditions. The expression of CD4 by canine neutrophils is without precedent in other mammalian species; the functional significance of neutrophil CD4 expression is puzzling in light of the current understanding of the functions of CD4 which include it's role as a receptor for nonpolymorphic regions of MHC class II molecules. PMID- 1412421 TI - DPB1*WA4--an additional HLA class II allele identified in west Africa. PMID- 1412423 TI - [The clinical case. Epistaxis, thoroughbred stallion, 4 years old]. PMID- 1412422 TI - [Ocular manifestations of selected zoonoses in humans]. AB - A report is given on the epidemiology and clinical signs of some selected zoonoses that may be of significance for ocular infections in man: brucellosis, leptospirosis, Lyme borreliosis, lymphocytic choriomeningitis, Newcastle Disease, ornithosis (chlamydiosis), rabies, Streptococcus suis infection, larva migrans ocularis by Toxocara canis or Baylisascaris procyonis, toxoplasmosis and tularemia. PMID- 1412424 TI - [The clinical case. Vomiting brown stomach contents. German shepherd dog, male, 2 years old]. PMID- 1412425 TI - [Diagnosis of hemostasis disorders]. PMID- 1412426 TI - [The occurrence of hyena disease in young cattle]. AB - Eight juvenile cattle with symptoms of hyena disease are described. This represents the first occurrence of the condition in the Republic of Poland. The growth of the affected animals was retarded, with a marked difference in longitudinal growth of the femoral, humeral, tibial and metatarsal bones. The animals showed altered nickel, manganese and inorganic phosphate concentrations, which may be related to the disease. The genetic studies did not reveal any aetiological factors. PMID- 1412427 TI - [Hysteroscopy as a diagnostic aid for uterine diseases of cattle]. AB - A method for hysteroscopy in cattle, using a rigid tube for passage through the cervical canal, is described. Using this method, passage through the cervical canal is possible independent of the stage of the gynaecological cycles. The hysteroscopic findings of 105 examinations in cows are described and discussed. PMID- 1412428 TI - [Myocardial fibrosis and degeneration with heart failure (cardiomyopathy) in two goats]. AB - Myocardial fibrosis and degeneration of unknown etiology is described in two adult, female goats of the Saanen and Pfauen breeds. Both animals presented with clinical signs of cardiac failure with subcutaneous edema, hydrothorax and ascites. The pathological lesions were characterized by cardiomegaly with ventricular and auricular dilatation and hypertrophy, massive subcutaneous edema and body cavity edema. The first goat additionally showed chronic liver congestion due to cardiac failure. Histologically, the most prominent changes were focally extensive cardiomyocyte degeneration and cardiac fibrosis. The clinical history and pathologic lesions are comparable to those of dilatative cardiomyopathy in SixRH cattle. PMID- 1412429 TI - [Detection of embryonic mortality in cattle using sonography]. AB - In 70 pregnant cattle the diameter of conceptus, the size of embryo and corpus luteum were estimated with a 5 MHz-linear array scanner on days 22, 25, 28, 35 and 42 (+/- 1 day) after insemination. Additionally, the milk progesterone level was determined. Embryonic mortality was found in 7 cases, in 3 cows on day 35, in 4 cows on day 42. The lack of embryonic heart beat was the first sign; later in pregnancy significant differences in sizes of conceptus and embryo compared with physiological pregnancies occurred. Membranes and bubble-like structures became visible in the lumen of the conceptus. The conceptus could be detected until the following oestrus, which began 8 to 42 days after embryonic death. The corpus luteum remained until proestrus. This correlated positively with the progesterone levels. PMID- 1412430 TI - [Epidemic late abortion in swine--status of research]. AB - This article briefly describes the PRRS (Porcine Reproductive and Respiratory Syndrome), which arose in the winter of 1990 in Germany and other European countries. The data are accumulated from the literature and own experiences. The clinical picture of this new disease, which led to important economical losses is dominated by 1. an increased rate of reduced length of pregnancy with late abortion before day 110 or an increased length of pregnancy; 2. an increase of stillborn piglets; 3. a larger scale of preweaning mortality combined with a higher frequency of secondary infections. Pathological findings in piglets are subcutaneous edema, accumulation of fluids in the body cavities and sometimes interstitial pneumonia is observed. In sows originating from affected farms examined before partus a mononuclear placentitis is present. At present a non classified virus, isolated by Dutch researchers is proposed to be the causative agent and named Lelystad virus. PMID- 1412431 TI - [Ocular manifestations of systemic diseases in birds. Part 1]. AB - Among the representatives of the class Aves ocular lesions may be a particularly strong indication of systemic disorders. A causative diagnosis of ocular lesions may be vital for the avian patient, not only as a basis for effective therapy of the primary disease, but also for saving the vision, as birds orientate themselves primarily by vision. The following paper presents a synopsis of important ocular disorders in avian patients that are either pathognomonic for certain disorders or, when considered in conjunction with other organic diseases, enable a specific diagnosis to be arrived at. In part 1 bacterial and parasitic etiologies will be described. Part 2 deals with viral infections and noninfectious etiologies. PMID- 1412432 TI - [Plasma gastrin levels in horses with colic]. AB - The plasma gastrin levels in fasted horses (21.1 +/- 15.6 pg/ml), in horses with spasmodic colic (7.3 +/- 5.4 pg/ml) and in horses with impaction of the left ventral large colon and/or pelvic flexure (11.4 +/- 3.1 pg/ml) were not significantly different. The plasma gastrin concentrations of horses with strangulation obstruction of the small intestine, large colon displacement or adynamic ileus, and which had no gastric reflux, were 12.9 +/- 8.7 pg/ml and did not differ from fasted gastrin levels. Horses which had 5-10 litres of stomach content reflux had a higher mean gastrin level (32.2 +/- 22.6 pg/ml) (range 8.7 83.0) than the fasted horses. The mean plasma gastrin level (69.0 +/- 32.2 pg/ml) (range 27.0-122.0 pg/ml) in horses which had gastric reflux and 11-20 litres of stomach content outflow through the nasogastric tube were significantly higher (P less than 0.0004) than in fasted horses or in horses with spasmodic colic, impaction of the left ventral large colon or in horses from which no gastric reflux could be obtained. PMID- 1412433 TI - [Early sonographic diagnosis of twin pregnancy in mares and its reduction to a single pregnancy]. AB - The frequency of double ovulation and the chances of twin pregnancy in the mare are presented with reference to the relevant literature. A novel manual technique for reducing the embryo number from two to one is introduced and illustrated by ultrasonographic images. PMID- 1412434 TI - [Double ovulation in mares. Clinical, hormone analytical and sonographic studies]. AB - 108 mares with a total of 135 oestrous cycles were examined. 30% of the mares showed development of double follicles, found by palpation and ultrasonography. Eight cases of double ovulation, four of them synchronous and four asynchronous, were examined closely. These cases of double ovulation showed different growth and different development of the follicular wall. This occurred at the same time in cases of synchronous double ovulation whereas it differed in case of asynchronous double ovulation. The later ovulating follicle was still growing while the first one had already burst. With both forms of double ovulation an equal concentration of progesterone was detected in peripheral blood. On the day of ovulation the rate of progesterone was low (1 ng/ml blood plasma) and it first started rising from the day +1 on. Double follicles matured slower than single follicles. Mares with synchronous double ovulation showed the typical oestrus behavior. This behavior was less distinct after the first ovulation in mares with asynchronous double ovulation. All four mares with asynchronous and two mares with synchronous double ovulation became pregnant. Twins did not occur. A possible relationship between double ovulation and twin pregnancy is discussed. PMID- 1412435 TI - [Pathology of the cornea]. AB - The basic pathologic mechanisms of corneal inflammation, including hereditary and degenerative-dystrophic keratopathies, are presented. Inflammatory keratopathies of non-ulcerative and ulcerative forms, which often occur in the ophthalmopathological diagnostics, are described, and special nosological entities are emphasized. The consequences of corneal ulceration are mentioned, and the incidence of neoplastic corneal processes is considered. PMID- 1412437 TI - [The blood supply to the stomach of the dog--a corrosion cast and scanning electron microscopic study]. AB - An unimpaired vascular circulation is vital for gastric function. The arteries of the stomach originate from the coeliac artery; the veins lead to the portal vein. Arteries in the right half of the organ form a perigastric circle of anastomosing vessels, which is lacking on the left side. The basal capillary network of the gastric submucosa shows no important regional differences. Territories of vascularisation are documented for the canine stomach. PMID- 1412436 TI - [Cytology of the cerebrospinal fluid in dogs with brain tumors and spinal cord compression. Part 4]. AB - The results of cerebrospinal fluid (CSF) cytology of 9 dogs with brain tumors and 50 dogs with spinal cord compression are discussed. Of the 50 dogs with spinal cord compression, disc protrusion was diagnosed in 31, myelomalacia in 7, discospondylitis in 3 and spinal cord tumors in 9 dogs. In 4 of 9 dogs with brain tumors, tumor cells could be found by the sedimentation apparatus of Kolmel. Pleocytosis existed in 6 patients. In about 70% (29 of 41) of cases with disc protrusion, more than 200 cells could be evaluated in the CSF sediment, consisting mostly of transformed lymphocytes and activated monocytes. As the neurologic deficits increased, the amount of cells and especially cell complexes increased. This was especially evident in cases with myelomalacia of the spinal cord. Only in cases with discospondylitis or spinal cord neoplasia was the CSF cytology unchanged. PMID- 1412438 TI - Kidney and hypertension. Festschrift on Professor Kaoru Yoshinaga's retirement. PMID- 1412439 TI - Calcium antagonists and the kidney. AB - Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonist exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment glomerular filtration rate but produce only a modest improvement in renal perfusion. Utilizing the isolated perfused hydronephrotic rat kidney model that permits direct visualization of afferent and efferent arterioles, we have demonstrated that this preferential augmentation of glomerular filtration rate is primarily attributable to a selective vasodilation of pre-glomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists may exert salutary effects on renal function in clinical settings that are characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk for the development of acute renal insufficiency remain to be evaluated. PMID- 1412440 TI - The diuretic effect of calcium entry blockade in normals and hypertensive patients. AB - Calcium entry blockers have been shown to exert hemodynamic and diuretic effects in the kidney. The diuretic effects can be demonstrated most clearly in the isolated perfused kidney, not influenced by compensatory mechanisms such as a lower blood pressure or changes of hormones. However, they can also be shown in vivo in humans. We studied the renal effects of calcium entry blockade after the first dosage and after continued oral dosages of 20 mg nicardipine tid in patients with essential hypertension and in normotensive controls. Renal function was determined during maximal free water clearance, allowing estimation of changes in "proximal" and "distal" tubular sodium reabsorption. Results showed a natriuretic effect. In the control subjects, clearance results were compatible with a decrease of proximal and distal tubular reabsorption, but in the hypertensive group natriuresis was mainly achieved by an increase of the glomerular filtration rate and a decrease of fractional distal reabsorption. In both groups the natriuresis occurred concomitantly with a lower blood pressure. The ratio plasma renin activity/plasma aldosterone concentration increased, although nicardipine did not inhibit the increase of plasma aldosterone during angiotensin II infusion. Pre-treatment with the calcium entry blocker nitrendipine enhanced the natriuretic effect of atrial natriuretic factor (ANF) in sodium replete normal volunteers. Facilitation of sodium excretion by human ANF may be an additional diuretic mechanism of calcium entry blockers. PMID- 1412441 TI - Systemic and renovascular hypertension. AB - To ascertain the contribution of systemic hypertension in the progression of renal failure, we have studied the effects of pharmacological treatment of hypertension in rats with the remnant kidney model of renal insufficiency, streptozotocin diabetes, or nephrotoxic serum nephritis. Treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril lowered systemic blood pressure in the remnant kidney and diabetic animals, but did not lower blood pressure in rats with nephrotoxic serum nephritis. Proteinuria was reduced in all three models, and creatinine clearance improved in the remnant kidney and diabetic animals, when compared with untreated controls. In the remnant kidney and diabetic models systemic blood pressure was lowered to a similar degree by treatments with a calcium blocker, with no improvement in either proteinuria, or glomerular filtration rate. Further studies of the long-term effects of enalapril have been undertaken in rats with the two kidney one clip model of hypertension. Rats treated with enalapril had a lower blood pressure and improved survival over one year of treatment, compared with untreated rats. After 1 year of treatment however the clipped kidney was small and fibrotic, and non functional. Following withdrawal of enalapril therapy there was no functional improvement of the clipped kidney. The possibility that ACE inhibitors have a specific intra-renal effect reducing the rate of progression of renal disease now needs confirmation in human studies. In renovascular hypertension however, intra-renal changes induced by ACE inhibitors may cause irreversible renal damage. PMID- 1412442 TI - Preservation of renal function in chronic renal failure. AB - Mechanisms of progression of chronic renal failure (CRF) have been well documented in the rat but may not be relevant in man. Factors which may modify clinical CRF include underlying disease, diet, hypertension, intercurrent events, and adverse or beneficial effects of drug therapy. It has been argued that progression in many forms of renal disease is inexorable below a certain level of renal function. In other diseases, eg primary malignant hypertension, analgesic nephropathy, function frequently improves in both the short and long term with appropriate management. Thus knowledge of the nature of the underlying disease is essential in assessing progression. The value of diet in preserving renal function has been debated, particularly the relative roles of protein and phosphate control. In our own unit, a prospective randomized study showed a benefit of protein restriction. Development of accelerated hypertension is an important cause of progression of renal disease and clinical and experimental evidence supports the view that non-accelerated hypertension is also a factor in progression, amenable to treatment. Various intercurrent events may accelerate progression and function may be lost permanently following sepsis, urinary tract obstruction, renal arterial or venous obstruction, hypotension and in some cases pregnancy. Numerous drugs can have deleterious effects on the kidney. The possibility that converting enzyme inhibitors might preserve renal function is attracting attention but in view of their side effects their place in therapy should be determined by prospective controlled studies in which the above factors are carefully considered. PMID- 1412443 TI - Localization of components of the renin-angiotensin system within the kidney and sustained release of angiotensins from isolated and perfused kidney. AB - We found colocalization of renin, angiotensin (Ang) I and Ang II in juxtaglomerular (JG) cells of the kidney. Coexistence of Ang II in renin granules was demonstrated by electron microscopic immunogold labeling of these components. Coexistence of both Ang I and Ang II in the high density renin storage granules were also demonstrated by gradient centrifugation of renal homogenate. These findings supported the synthesis of Ang I and Ang II in juxtaglomerular cells. Isolated and cultured JG cells showed the synthesis of Ang I, Ang II and renin. Ang I and Ang II were secreted from isolated and perfused rat kidneys at steady rates over 2 hr. Their secretion rates were proportional to that of renin. The rate of Ang II secretion from the kidney was higher than that from the vascular bed. Ang II was also found in renal lymph. These findings indicate that a large amount of Ang II is generated in JG cells by the intracellular action of renin and may play a significant role in the regulation of renal function. PMID- 1412444 TI - Effect of sulindac on prostaglandin synthesis in human and in cultured rat renal and vascular smooth muscle cells. AB - To examine the hypothesis that sulindac does not inhibit renal prostaglandin (PG) synthesis, we investigated the effects of sulindac and other nonsteroidal anti inflammatory drugs on PG synthesis in human and in cultured rat renal and vascular smooth muscle (VSM) cells. In 7 patients with chronic glomerular disease, creatinine clearance and proteinuria were not changed by sulindac but were significantly reduced by diclofenac sodium. However, urinary excretion of PGE2 was decreased by both drugs. In cultured glomerular mesangial (GM), renal papillary collecting tubule (RPCT) and VSM cells from mesenteric artery, indomethacin, tiaprofenic acid, aspirin and ibuprofen inhibited both basal and arachidonic acid (AA)-stimulated PG synthesis dose-dependently. Although sulindac sulfoxide, at the same concentrations, inhibited both basal and AA-stimulated PGE2 synthesis in RPCT cells, it was less potent to inhibit PGI2 synthesis in VSM cells or PGE2 synthesis in GM cells. Active form sulindac sulfide inhibited PG synthesis in all types of cells but its inactive form sulfone did not. We conclude that sulindac inhibits renal PG synthesis but has little effect on renal function. This may be explained by its relatively weak potency on glomerular or vascular PG synthesis inhibition possibly due to the different biotransformation of the sulfoxide to the active sulfide in these cells. PMID- 1412445 TI - Macula densa control of renin release and glomerular hemodynamics. AB - In each nephron of the mammalian kidney, the tubule returns to the hilus of the parent glomerulus, forming the juxtaglomerular apparatus (JGA). The JGA displays a unique arrangement of afferent and efferent arterioles, interstitial cells and macula densa (a specialized plaque of tubular epithelial cells). Because of this intimate anatomical relationship, it has long been suggested that the macula densa may somehow sense changes in the composition of the tubular fluid and control both the glomerular filtration rate and renin release. Despite extensive investigation, attempts to obtain direct evidence of this have been hindered by the anatomical complexity of the JGA. However, recent technical developments now permit direct assessment of the role of the macula densa in the control of both renin release and glomerular hemodynamics. These developments include microdissection/perfusion of the afferent arteriole, the macula densa or both, as well as a sensitive renin assay which permits measurement of renin release from a single JGA. Observations resulting from such developments are discussed in this article. PMID- 1412446 TI - Localization and regulation of renal receptors for angiotensin II and atrial natriuretic peptide. AB - The anatomical distribution of receptors for angiotensin II (Ang II) and atrial natriuretic peptide (ANP) within the kidney has been investigated by in vitro autoradiography. Ang II and ANP receptor binding occurs together in several sites in the kidney, including renal vasculature, glomeruli, proximal convoluted tubule of the outer cortex, and the vasa recta bundles of the inner stripe of the outer medulla. However, in the glomeruli, Ang II receptor binding occurs predominantly in mesangial cells, while ANP receptors are localized mainly to the visceral epithelial cells. In the inner medulla, there is a moderate density of ANP receptors in marked contrast with Ang II binding which is not detected in this site. Both Ang II and ANP receptors are modulated by alterations in sodium and fluid intake, and the peptides themselves. The overlapping distribution of receptors for these two peptide hormones in several intrarenal sites may provide an anatomical basis for their physiological interaction to regulate renal hemodynamics and tubular reabsorption of sodium and water. PMID- 1412447 TI - Eicosanoids, mesangial contraction, and intracellular signal transduction. AB - The glomerular mesangial cell is a specialized pericyte with multiple functional capabilities including contraction. Mesangial contraction may reduce the glomerular filtration surface area and hence the ultrafiltration coefficient, Kf. Cultured mesangial cells convert arachidonic acid into biologically active eicosanoids which are either contractile (thromboxane A2 [TxA2], prostaglandin F2 alpha [PGE2 alpha]) or relaxant (PGE2, PGI2). The addition of TxA2 analogues, PGE2 or sulfidopeptide leukotrienes (LTC4 and LTD4) stimulated contraction of cultured mesangial cells with threshold responses at approximately 1 nM and maximum responses at 1 microM. PGE2 and PGI2 antagonized mesangial contraction induced by TxA2 analogues. Contraction was enhanced by inhibiting mesangial cyclooxygenase with nonsteroidal antiinflammatory drugs (NSAID). Contractile eicosanoids stimulated phospholipase C thereby elevating intracellular inositol trisphosphate and cytosolic free Ca2+ concentration ([Ca2+]i). Vasorelaxant prostanoids stimulated adenylate cyclase, increasing intracellular cyclic AMP. We conclude that eicosanoids control mesangial contractility by regulating [Ca2+]i and cAMP. NSAID increase mesangial reactivity by blocking the inhibitory effects of endogenous vasodilator eicosanoids, with potential consequences on glomerular hemodynamics. PMID- 1412448 TI - Functions of ascending thin limb of Henle's loop with special emphasis on mechanism of NaCl transport. AB - Major controversy concerning the ascending thin limb of Henle's loop (ATL) centers on the urine concentration mechanism based on the countercurrent multiplier system in the inner medulla of the kidney. This renal tubular segment has specific transport properties which function to dilute the urine without any movement of water across the epithelium. This segment is fundamentally impermeable to water, moderately permeable to urea, and highly permeable to Na+ and Cl-. Whether NaCl is reabsorbed actively in the ATL has long been an important question. While mathematical modelling studies have failed to explain completely how the osmotic gradient in the inner medulla is generated without active NaCl transport in the ATL, the experimental data support the view that active NaCl reabsorption is absent. Recently, we succeeded in measuring the intracellular Na+ concentration by using the fluorescent Na+ indicator sodium binding benzofuran isophthalate in the in vitro microperfused ATL. Our data suggest that the ATL maintains a low intracellular Na+ concentration by the ouabain-sensitive Na+/K+ ATPase in the basolateral membrane, and that the luminal membrane of the ATL has furosemide-insensitive Na+ permeability. Active Na+ reabsorption estimated in our study amounts to only a few per cents of the net Na+ reabsorption in the ATL. It is therefore suggested that the major role of Na+ extrusion in the ATL cells is to maintain a low cellular Na+ concentration against ambient hyperosmolarity, although small but substantial amount of Na+ is reabsorbed by the furosemide-insensitive Na+ permeability and ouabain-sensitive Na+/K+ ATPase. PMID- 1412449 TI - Effect of acute and chronic treatment of tin on blood pressure in spontaneously hypertensive rats. AB - Cytochrome P450-dependent metabolites of arachidonic acid (AA) are increased in the kidneys of spontaneously hypertensive rats (SHR) as compared to control rats (WKY) in the period of rapid elevation of blood pressure (BP) from 5 to 13 weeks. We treated rats with stannous chloride (SnCl2) (10 mg/100 g body weight/day for 4 days) to decrease selectively renal cytochrome P450 content through increasing renal heme oxygenase activity. A decrease in renal cytochrome P450-dependent AA metabolites was associated with decreased BP and increased urinary Na+ excretion in 7- but not in 20-week-old SHR rats. Chronic treatment with SnCl2 (10 mg/100 g body weight twice a week) from 5 to 20 weeks prevented the elevation of BP in SHR rats. Further, the antihypertensive effects of tin persisted for 7 weeks beyond its discontinuation. BP in WKY rats was unaffected by tin. Both the acute and chronic treatment with tin are the first studies to demonstrate amelioration of hypertension in SHR by an intervention which is targeted at a single enzyme system. PMID- 1412451 TI - Experimental studies on carcinogenesis in anomalous arrangement of the pancreaticobiliary ducts. AB - An experimental model of anomalous arrangement of the pancreaticobiliary ducts (APBD) was produced by pancreaticocholecystostomy performed in 29 mongrel dogs. Our purpose was to study carcinogenesis of the extrahepatic biliary tract by DNA ploidy analysis with cytofluorometry. The amylase level in the bile was elevated in all 25 dogs tested except the controls. The phospholipase A2 level in the bile was elevated in all selected dogs except the controls. Common bile duct (CBD) dilatation was found in 23/29 (79%) of the dogs, and biliary stones were found in 3/29 (10%) dogs. Inflammatory changes were observed microscopically in all specimens except those from the controls. Intramural glandular structures were found in 17/25 (68%) of gallbladder (GB) specimens and 10/25 (40%) of CBD specimens; goblet cells were found in 7/25 (28%) of GB specimens and 2/25 (8%) of CBD specimens. In the controls neither glandular structures nor goblet cells were observed except for two GB specimens showing mild cholecystitis. Cytofluorometry showed 21% GB and 7% CBD diploidy, 69% GB and 65% CBD low ploidy, 10% GB and 28% CBD high ploidy patterns of histograms. These results show that, APBD may be central to high risk condition or play a key role to develop atypical biliary tract epithelium and DNA ploidy abnormality with or without biliary duct dilatation. PMID- 1412450 TI - Roles of renal cytochrome P450-dependent arachidonic acid metabolites in hypertension. AB - Cytochrome P450 represents the third metabolic pathway of arachidonic acid giving rise to several biologically active compounds, such as 19-HETE, 20-HETE and EETs and their corresponding DHETs. The kidney is the rich source of these metabolites which have some important biologic actions within the kidney. These metabolites have a wide and contrasting spectrum of biological and renal effects, from vasodilation to vasoconstriction and from inhibition to stimulation of Na-K ATPase, their relative production rates may influence not only renal hemodynamics but also pro- and anti-hypertensive mechanisms of hypertension. There is increasing evidence that the abnormality of these metabolites in animal models of hypertension. However, sufficient evidence of the physiological and pathophysiological roles of hypertension in man is still lacking. PMID- 1412452 TI - Correlation of carotid B-mode scanning with endarterectomy findings in Japanese patients. AB - In this study, 13 Japanese patients who underwent carotid endarterectomy with en bloc method were prospectively evaluated by high-resolution B-mode scanning. B mode imaging was carried out 1-2 days before operation. The most suitable consecutive longitudinal planes of the carotid bifurcation were photographed (5-8 planes). The echogain was gradually changed from a lower to a higher intensity during B-mode scanning to identify the echogenicity of the atheromatous plaques. Three-dimensional reconstructions were made of the carotid plaques before performing carotid endarterectomy, and the author investigated the correlations between the echo characteristics and the histology of the resected plaques. The echogenicity of all atheromatous plaques, except for those with calcification, was lower than that of the normal medial layer of the vessel wall. The consecutive B-mode image data correlated well with the histological findings of the resected plaques in this study. In 2 out of 13 cases, it was found to be very difficult to distinguish an ulcerated plaque from a region of fresh intraplaque hemorrhage. High-resolution B-mode scanning was found to be a very useful and reliable method for identifying the detailed structure of atheromatous plaques in the cervical carotid artery. PMID- 1412453 TI - Clinical appraisal of stereotactic hematoma aspiration surgery for hypertensive thalamic hemorrhage--with respect to volume of the hematoma. AB - Three hundred and four patients with hypertensive thalamic hemorrhage were managed by medical treatment, ventricular drainage, or CT-controlled stereotactic aspiration surgery (AS). The therapeutic results of the 6-month outcome were analyzed and correlated with the volume of the hematoma. A hematoma volume of 20 ml was thought to be the critical size in determining whether the outcome would be favourable or unfavorable. Indications for AS are suggested as follows. In patients with a small-sized hematoma having a volume of less than 10 ml use of AS should be restricted to patients with severe paralysis or other neurological complications and the elderly (aged 70 years or older). For patients with a medium-sized hematoma having a volume between 10 ml and 20 ml, AS is indicated for patients having severe paralysis and disturbances of consciousness. For patients with a large-sized hematoma having a volume of 20 ml or more, AS increases not only the survival rate of patients but also reduces the number of bedridden patients. We conclude that AS opens up a new avenue of surgical treatment for hypertensive thalamic hemorrhage, which has been no indication for hematoma evacuation by conventional craniotomy. PMID- 1412454 TI - Accuracy of the results measured by in vivo 1H-MRS using model solutions. AB - In in vivo 1H-MRS of human brain, main three metabolites such as N-acetyl-L aspartate (NAA), creatine/phosphocreatine (PCr/Cr), and choline (Cho) have been observed. In this paper an accuracy of the results measured by in vivo 1H-MRS using above model solutions was discussed. 1.0 mmol/l choline and 1.5 mmol/l creatine/phosphocreatine saline solutions were measured with STEAM method (echo time 270 msec). The peak area of Cho was larger than that of PCr/Cr against their concentrations and was linearly increased with its concentration in the range of 5.8 and 29 mumol/27 cm3. Although both peak areas of Cho and Cr/PCr were varied with Volume-of-interest (VOI) coordinates, the ratio of Cho to PCr/Cr was approximately 1.6. PMID- 1412455 TI - Glutamine antagonist with diet deficient in glutamine and aspartate reduce tumor growth. AB - This study was designed to investigate whether a combination of a glutamine antagonist (DON) and a diet deficient in glutamate and aspartate (AG) altered glutamine metabolism in tumor tissue, and inhibited tumor growth. In experiment 1, 21 male Donryu rats were fed with AG and implanted with Yoshida's Sarcoma. Of them, 7 rats were sacrificed on the 5th day (group AG), other 7 were sacrificed next day (group AG-1) and the remaining 7 were injected with DON on the 5th day and sacrificed next day (group AG+D). The tumor weight of group AG+D was significantly lower than of group AG, or of group AG-1. In experiment-2, of 23 rats, 9 were fed with control diet and 14 were fed with AG and implanted. 12 were sacrificed on the 5th day (group C, AG), and 11 were injected with DON on the 5th day and sacrificed next day (group C+D, AG+D). The reduced ratio of tumor weight in group C+D and group AG+D were 25% and 67%, respectively. These results show that the tumor growth could be inhibited by using metabolic antagonist of glutamine, and that it had synergistic effect in conjunction with the imbalanced diet. PMID- 1412456 TI - Comparison of cytofluorometric nuclear DNA ploidy analysis on fresh and paraffin embedded specimen. AB - The cytofluorometric nuclear DNA ploidy analysis was performed in gallbladder (GB) epithelium of eight patients of chronic cholecystitis to make a comparison between fresh and paraffin embedded tissue analysis, to make an ideal single cellular suspension, to evaluate the ploidy pattern affected by inflammation and to assess the histological correlations. Six (75%) fresh specimens and eight (100%) paraffin embedded specimens showed diploidy pattern of histogram. Two (25%) fresh specimens showed low ploidy pattern of histogram. There was a good correlation between histological findings and the ploidy patterns of 100% paraffin embedded specimens and 75% fresh specimens. The relative fluorescence intensity was found higher and more stable in paraffin embedded tissues than fresh tissues. Inflammation did not affect the ploidy patterns of paraffin embedded specimens whereas the ploidy patterns of fresh specimens were affected. It can be concluded that the DNA ploidy patterns and histological findings have a good correlation and inflammation does not affect the cytofluorometric DNA ploidy pattern when using the paraffin embedded specimens. Paraffin embedded specimens are superior to fresh specimens for making an ideal single cellular suspension to obtain stable, high, and accurate fluorescence intensity with less background fluorescence which makes the ploidy pattern behave like exact behavior of tissues. PMID- 1412457 TI - Quantified application of MRI for diagnosis of head and neck tumors. AB - We evaluated T/M ratios and T2 values of 6 malignant lymphomas and 8 squamous cell carcinomas in the head and neck in order to differentiate these two entities. T/M ratios were calculated by dividing intensity of tumor by that of muscle in same slice images. T2 values were calculated from T2-weighted images and proton-weighted images. Statistical difference of T/M ratios was found between malignant lymphomas and squamous cell carcinomas, but no difference of T2 values was seen between two groups. T/M ratio was considered to be a useful and quantified index for evaluation of head and neck tumor. PMID- 1412458 TI - Protein deficiency and excess lipid synergistically augmented lipid peroxidation in growing rats. AB - The influence of dietary protein and lipid on superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH) and tissue lipid peroxidation, as measured by thiobarbituric acid-reactive substances (TBARS), was investigated in post-weaning male Wistar rats, fed either a diet containing 5% or 20% corn oil with 5%, 10% or 20% soy protein isolate (SPI) for four weeks. TBARS concentrations in 5% corn oil group was highest in 5% SPI group for all organs, followed by 10 and 20% SPI groups in the liver and 10 and 20% SPI groups in other organs. High lipid diet significantly increased TBARS formation in the liver of 10% SPI group. The liver and kidney SOD and GPx activities were higher in 5% and 10% SPI groups than in 20% SPI group, suggesting an augmented formation of radical substrates for these enzymes in low protein groups. Organ GSH concentrations did not show a linear correlation with dietary protein level. These results suggest that protein deficiency along with high lipid intake accelerates the peroxidative damage of the tissues by increasing oxy-radical formations and/or decreasing the defense mechanism. PMID- 1412459 TI - Intramedullary spinal cord metastasis from lung cancer presenting with paraparesis: an autopsied case. AB - A 75-year-old male presented with paraparesis and pain in the thighs, which progressed rapidly. Five days later, he was unable to stand or to void urine. A lung cancer was found in the right upper lobe. A spinal cord metastasis from the lung cancer was suspected from the neurologic and pulmonary findings. After 2 weeks, motor dysfunction and a total sensory deficit were observed below the lumbar region, and the patient developed pneumonia, which resulted in death. Autopsy showed an extensive intramedullary metastasis at the third lumbar segment of the spinal cord. Histology revealed poorly differentiated adenocarcinoma of the lung. PMID- 1412460 TI - Human and experimental studies on renal eicosanoid response to long-term cadmium exposure. AB - In order to assess the effects of long-term exposure to cadmium (Cd) on the renal metabolism of eicosanoids, the urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2) was determined in 37 workers exposed to Cd and in female Sprague-Dawley rats given 100 ppm Cd in drinking water for 10 months. Urinary output of sodium and calcium was also determined. The Cd-exposed workers showed an increased urinary concentration of 6-keto-PGF1 alpha, PGE2, sodium, and calcium. The rise of 6-keto-PGF1 alpha was related to Cd levels in blood and weakly correlated with urinary sodium. Calcium in urine was not related to the concentration of the metal in blood and urine. A slight elevation in urinary TXB2 was also observed in workers with blood Cd higher than 5 micrograms/liter. After 10 months of exposure to Cd, female Sprague-Dawley rats presented an enhanced urinary excretion of albumin, transferrin, beta 2-microglobulin, sodium, and PGE2 in urine. The latter was significantly correlated with albuminuria and transferrinuria. In conclusion the results show that chronic exposure to Cd induces changes in the urinary excretion of some eicosanoids. The possible relation of these changes to Cd-induced kidney dysfunction are discussed. PMID- 1412461 TI - Altered capillary filtration coefficient in parathion- and paraoxon-induced edema in isolated and perfused rabbit lungs. AB - Changes in pulmonary endothelium permeability and in microvascular hemodynamics induced by parathion (Pth) and paraoxon (Pox), its active metabolite, were investigated in isolated, perfused rabbit lungs. Blood-free perfusate was recirculated through isolated and ventilated lungs in an isogravimetric state and in zone III conditions. The arterial/venous/double occlusion technique was used to divide the total vascular resistance (Rt) into four components: arterial, precapillary, postcapillary, and venous. The capillary filtration coefficient (Kfc) was evaluated by measuring the amount of fluid filtering through the endothelium when the arterial and venous pressures were suddenly increased. Pth and Pox induced pulmonary edema by increasing endothelium permeability without changing the hemodynamic parameters at any level of the vascular bed. The Kfc value increased progressively, reaching a maximum (Emax) 60 min after administration of organophosphate (558 +/- 65% (n = 5) and 707 +/- 109% (n = 5) of baseline values, for Pth and Pox, respectively). During the next 60 min, it decreased. The time course of Pox-induced changes in Kfc was similar to that obtained with Pth. The concentration-response curve (Emax) expressed as a percentage of the baseline value versus the logarithm of the molar Pth concentration, ranging from 2 x 10(-5) to 4 x 10(-4) M) was linear (y = 1661.1 + 327.3x, r = 0.89, p < 0.001, n = 14). Piperonyl butoxide (4 x 10(-4) M), an inhibitor of cytochrome P450, had a strong protective effect against Pth (4 x 10( 4) M)-induced alterations of endothelium permeability (n = 5, p < 0.001). The effects of Pox (4 x 10(-4) M) on Kfc were completely abolished by pretreatment with 10(-5) M atropine, as shown by the significantly lower Emax value recorded in atropine-pretreated lungs (129 +/- 33%, n = 4) than in Pox-treated lungs (707 +/- 109%, n = 5, p < 0.001). The effects of Pth, on the other hand, were only partially inhibited, since the Emax value recorded in atropine-pretreated lungs (196 +/- 20%, n = 4) remained significantly higher than that recorded for control lungs (129 +/- 15%; n = 5; p < 0.05). These results show that isolated and perfused rabbit lungs constitute an appropriate model for studying the direct pulmonary effects of organophosphates. The edema-inducing action of Pth depends on its activation by conversion to Pox in the lung tissue.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1412462 TI - A physiologically based pharmacokinetic model for nicotine disposition in the Sprague-Dawley rat. AB - A physiologically based pharmacokinetic (PBPK) model was developed to describe the disposition of nicotine in the Sprague-Dawley (SD) rat. Parameters for the model were either obtained from the literature (blood flows, organ volumes) or determined experimentally (partition coefficients). Nicotine metabolism was defined in the liver compartment by the first-order rate constants KNC and KNP which control the rate of nicotine metabolism to cotinine and "polar metabolites" (PM), respectively. These rate constants were estimated by optimizing the model fit to pharmacokinetic data obtained by administering an intraarterial (S)-[5 3H]nicotine bolus of 0.1 mg/kg to 6 rats. Model simulations that optimized for the appearance of cotinine in plasma estimated KNC and KNP to be 75.8 and 24.3 hr 1, respectively. Use of these constants in the model allowed us to accurately predict nicotine plasma kinetics and the fraction of the dose eliminated by renal (8.5%) and metabolic (91.5%) clearance. To validate the model's ability to predict tissue kinetics of nicotine, 21 male SD rats were administered 0.1 mg/kg (S)-[5-3H]nicotine intraarterially. At seven time points following treatment, 3 rats were euthanized and tissues were removed and analyzed for nicotine. Model predicted nicotine tissue kinetics were in agreement with those determined experimentally in muscle, liver, skin, fat, and kidney. The brain, heart, and lung exhibited nonlinear nicotine elimination, suggesting that saturable nicotinic binding sites may be important in nicotine disposition in these organs. Inclusion of saturable receptor binding expressions in the mathematical description of these compartments resulted in better agreement with the experimental data. The Bmax and KD estimated by model simulations for these tissues were brain, 0.009 and 0.12; lung, 0.039 and 2.0; and heart, 0.039 nmol/tissue and 0.12 nM, respectively. This PBPK model can successfully describe the tissue and plasma kinetics of nicotine in the SD rat and will be a useful tool for pharmacologic studies in humans and experimental animals that require insight into the plasma or tissue concentration-effect relationship. PMID- 1412463 TI - Characterization of lewisite toxicity in isolated perfused skin. AB - Lewisite (L) is a potent organic arsenical that causes rapid onset of pain and severe vesication on contact with epithelial tissues. The isolated perfused porcine skin flap (IPPSF) is an in vitro model that has shown potential as a model for cutaneous vesicant research. The objective of this study was to characterize IPPSF responses after topical exposure to six concentrations of L ranging from 0.07 to 5.0 mg/ml (n = 4/treatment plus controls). Biochemical markers of viability (glucose utilization (CGU) and lactate dehydrogenase (LDH) release), vascular resistance (VR), venous arsenic flux, and morphological parameters (light and electron microscopy) were evaluated. In addition, lewisite lesions were characterized at 1, 3, 5, and 8 hr after exposure (n = 4/time plus controls) using these morphological parameters, as well as enzyme histochemistry. Macroscopic and microscopic lesions caused by L exposure were dose related. Mild decreases in CGU were noted with the higher concentrations of L, while generally increased responses in LDH release and VR were seen. Marked increases in LDH activity were noted in the blister fluid of IPPSFs treated with 5.0 mg/ml of L. Also, significant cutaneous arsenic flux was noted at the 5.0 mg/ml dose of L. The formation of gross blisters, the location and characterization of epidermal dermal junction separation, and the time course of lesion production paralleled the description of L-induced lesions in humans. The sensitivity of the IPPSF to L exposure and the similarity of lesions to those described for humans suggests that this model provides a relevant in vitro model with which to study mechanisms of chemical vesication and arsenic toxicity, as well as protective and therapeutic intervention for vesicant exposure. PMID- 1412464 TI - Inhibition of calcium-dependent pathways of B-cell activation by DMBA. AB - The purpose of the experiments described in these studies was to determine the effects of 7,12-dimethylbenz[a]anthracene (DMBA) on B-cell activation produced by anti-IgD antibodies and interleukin-4 (IL-4). B and T cells are known to share many of the same biochemical pathways for cell activation by mitogen and antigen receptors. Previous studies in this laboratory have shown that DMBA inhibits mitogen-induced Ca2+ mobilization in murine and human T cells and produces an increase in intracellular Ca2+ in resting cells. The results of the present studies demonstrate that DMBA increases Ca2+ in resting B cells and inhibits B cell activation produced by anti-IgD antibodies, as measured by mobilization of free intracellular Ca2+ and [3H]thymidine incorporation. The proliferative response of B cells to insolubilized anti-IgD was suppressed only when cells were preexposed to DMBA. In contrast, IL-4 pathways of B-cell activation were insensitive to inhibition by DMBA, even when cells were preexposed. The induction of Class II MHC antigen (Ia) antigens on B cells by IL-4 was also found to be insensitive to DMBA treatment. These results suggest that DMBA suppresses only Ca(2+)-dependent pathways of B cell activation and indicate that altered Ca2+ homeostasis may be responsible for immunosuppression induced by this agent. PMID- 1412465 TI - Differences in pulmonary biochemical and inflammatory responses of rats and guinea pigs resulting from daytime or nighttime, single and repeated exposure to ozone. AB - Rats and guinea pigs were exposed to 0.8 mg ozone (O3)/m3 (approximately 0.4 ppm) for 12 hr during the daytime, 12 hr during the nighttime, or continuously to investigate circadian variation in O3-induced pulmonary toxicity during single and repeated O3 exposures. Biomarkers in bronchoalveolar lavage (BAL) fluid and lung tissues were measured as indicators of biochemical and inflammatory responses. Nighttime O3 exposure of rats resulted in larger increases of protein, albumin, and inflammatory cells in BAL fluid compared to those after daytime O3 exposure and this daytime-nighttime difference was statistically significant (p < 0.05). Single daytime or nighttime O3 exposure of guinea pigs resulted in comparable increases of BAL fluid proteins and inflammatory cells without a daytime-nighttime difference. Nighttime and continuous O3 exposure of rats for 3 days resulted in comparable increases in lung antioxidant enzyme activities, both of which differed statistically from effects from daytime O3 exposures (p < 0.05). Continuous O3 exposure of guinea pigs for 3 days caused, in general, statistically larger increases in lung tissue parameters compared to nighttime O3 exposures (p < 0.05). These results suggest that the extent of O3-induced acute pulmonary biochemical and inflammatory responses is directly related to the level of physical and respiratory activity. For rats, effects from continuous O3 exposure appear to be controlled by the nighttime, physically active period. In guinea pigs, the comparable responses following daytime or nighttime O3 exposure seem in accordance with their random behavioral daily activity pattern. This study supports the view that physical activity-related increases in inhaled dose significantly enhance the pulmonary O3 responses. PMID- 1412466 TI - Enantioselective induction of peroxisomal proliferation in CD-1 mice by leukotriene antagonists. AB - The effects of a racemic leukotriene antagonist (MK-0571) and its component enantiomers (L-668,018 and L-668,019) on hepatic peroxisome proliferation were examined in mice, rats, and rhesus monkeys. Administration of racemic MK-0571 to mice resulted in increased liver weights, increased peroxisomal volume density, and a pleiotropic induction of characteristic peroxisomal and nonperoxisomal enzyme activities associated with peroxisomal proliferation. When the individual enantiomers of MK-0571 were administered to mice, a pronounced enantioselective induction of peroxisome proliferation was observed. Toxicokinetic studies showed that the levels of each enantiomer in the liver or plasma after separate administration were similar. Thus, the enantioselectivity in the induction of peroxisome proliferation could not be explained on the basis of pharmacokinetic differences between the enantiomers. The hepatic peroxisomal response of the rat to MK-0571 was greatly attenuated compared to the mouse. As has been seen with other peroxisome-proliferating agents, MK-0571 had no effect on either peroxisomal volume density or peroxisomal enzyme activity in monkeys. Due to the high degree of enantiomeric discrimination toward the induction of peroxisomal proliferation by these enantiomers, compounds of this type may prove useful as probes to examine the mechanisms by which peroxisomal proliferating agents induce their effects. PMID- 1412467 TI - Pulmonary cellular effects in rats following aerosol exposures to ultrafine Kevlar aramid fibrils: evidence for biodegradability of inhaled fibrils. AB - Previous chronic inhalation studies have shown that high concentrations of Kevlar fibrils produced fibrosis and cystic keratinizing tumors in rats following 2-year inhalation exposures. The current studies were undertaken to evaluate mechanisms and to assess the toxicity of inhaled Kevlar fibrils relative to other reference materials. Rats were exposed to ultrafine Kevlar fibers (fibrils) for 3 or 5 days at concentrations ranging from 600-1300 fibers/cc (gravimetric concentrations ranging from 2-13 mg/m3). A complete characterization of the fiber aerosol and dose was carried out. These measurements included gravimetric concentrations, mass median aerodynamic diameter, fiber number, and count median lengths and diameters of the aerosol. Following exposures, cells and fluids from groups of sham- and fiber-exposed animals were recovered by bronchoalveolar lavage (BAL). Alkaline phosphatase, lactate dehydrogenase (LDH), protein, and N-acetyl glucosaminidase (NAG) values were measured in BAL fluids at several time points postexposure. Alveolar macrophages were cultured and studied for morphology, chemotaxis, and phagocytosis by scanning electron microscopy. The lungs of additional exposed animals were processed for deposition, cell labeling, retained dose, and lung clearance studies, as well as fiber dimensions (from digested lung tissue), histopathology, and transmission electron microscopy. Five-day exposures to Kevlar fibrils elicited a transient granulocytic inflammatory response with concomitant increases in BAL fluid levels of alkaline phosphatase, NAG, LDH, and protein. Unlike the data from silica and asbestos exposures where inflammation persisted, biochemical parameters returned to control levels at time intervals between 1 week and 1 month postexposure. Macrophage function in Kevlar-exposed alveolar macrophages was not significantly different from sham controls at any time period. Cell labeling studies were carried out immediately after exposure, as well as 1 week and 1 month postexposure. Increased pulmonary cell labeling was measured in terminal bronchiolar cells immediately after exposure but returned to control values 1 week later. Fiber clearance studies demonstrated a transient increase in the numbers of retained fibers at 1 week postexposure, with rapid clearance of fibers thereafter. The transient increase in the number of fibers could be due to transverse cleaving of the fibers, since the average lengths of retained fibers continued to decrease over time. In this regard, a progressive decrease in the mean lengths and diameters of inhaled fibers was measured over a 6-month postexposure period.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1412468 TI - Lead inhibits secretion of osteonectin/SPARC without significantly altering collagen or Hsp47 production in osteoblast-like ROS 17/2.8 cells. AB - In an effort to better understand the consequences of lead (Pb2+) on skeletal growth, the effects of Pb2+ were investigated using ROS 17/2.8 bone-like cells in vitro. These studies revealed that Pb2+ (4.5 x 10(-6) M -4.5 x 10(-7) M) has little or no effect on cell shape except when added immediately following seeding of the cells. However, proliferation of ROS cells was inhibited, in the absence of serum, at concentrations of 4.5 x 10(-6) M Pb2+. Protein production was generally increased, however, the major structural protein of bone, type I collagen, production was only slightly altered. Following treatment of ROS cells with Pb2+, intracellular levels of the calcium-binding protein osteonectin/SPARC were increased. Osteonectin/SPARC secretion into the media was delayed or inhibited. Coincident with retention of osteonectin/SPARC there was a decrease in the levels of osteonectin/SPARC mRNA as determined by Northern analysis. These studies suggest that processes associated with osteonectin/SPARC translation and secretion are sensitive to Pb2+. PMID- 1412469 TI - Metabolism of benzo[a]pyrene by murine splenic cell types. AB - The objective of the present study was to determine which splenic cell type(s) of B6C3F1 mice was capable of metabolizing B(a)P. Separation of splenocytes based on density by centrifugation through discontinuous Percoll gradients along with immunomagnetic negative selection or antibody-mediated complement lysis was utilized to obtain highly enriched populations of splenocytes for B(a)P metabolism studies. Immunofluorescent cell staining in conjunction with flow cytometry and examination of Giemsa-stained cytospin cell preparations indicated that B- or T-cell populations of greater than 95% purity and an 80-90% pure population of splenic macrophages were routinely attained. Splenic cell populations were incubated with [3H]B(a)P for 24 hr. High-pressure liquid chromatography was used to separate and quantitate the B(a)P metabolites generated by the enriched splenic cell populations. The results of these studies demonstrate that the macrophage is the cell type responsible for the metabolism of B(a)P within the spleen. The major metabolites of B(a)P produced were as follows: an unidentified peak of polar metabolites containing polyhydroxylated metabolites, B(a)P-9,10-dihydroxy-9,10-dihydrodiol, and B(a)P-7,8-dihydroxy-7,8- dihydrodiol. Other splenic cell types examined, including B and T cells, polymorphonuclear cells, or the spleen capsule did not produce amounts of B(a)P metabolites significantly above background levels. Based on these findings, macrophages are the splenic cell types which metabolize B(a)P. As a result, macrophages may be the cell type targeted by B(a)P resulting in suppression of splenic humoral immune responses. PMID- 1412471 TI - 1992 Arnold J. Lehman Award. Roger O. McClellan. PMID- 1412472 TI - 1992 Burroughs Wellcome Fund Toxicology Scholar Award. Janice Chambers. PMID- 1412470 TI - Evaluation of murine splenic cell type metabolism of benzo[a]pyrene and functionality in vitro following repeated in vivo exposure to benzo[a]pyrene. AB - Recent studies have demonstrated that macrophages are the cell types capable of metabolizing benzo[a]pyrene (B(a)P) within the spleens of untreated mice. Since repeated exposure to B(a)P results in immunosuppression and B(a)P is known to induce cytochrome P450 levels, the first objective of this study was to investigate whether exposure of mice to B(a)P could increase the amounts of immunosuppressive B(a)P metabolites generated and/or alter the pattern of B(a)P metabolites formed by several different splenic cell types. Mice were dosed with a daily sc dose of 200 mg/kg B(a)P or vehicle for 4 days. Separation of splenocytes based on density by centrifugation through discontinuous Percoll gradients along with immunomagnetic negative selection or antibody-mediated complement lysis was used to obtain different splenic cell populations. Cells were incubated with [3H]B(a)P for 24 hr. High-pressure liquid chromatography was used to separate and quantitate B(a)P metabolites. Results indicate that splenic macrophages of B(a)P-treated mice produced significantly greater amounts of some metabolites compared to those of vehicle-treated mice. The three major metabolites produced were an unidentified peak of polar metabolites containing polyhydroxylated metabolites, B(a)P-9,10- and B(a)P-7,8-dihydrodiols. Other splenic cell types examined did not produce metabolite amounts significantly above (T-cells, PMNs, or the capsule) or just above (B-cells) background. The second objective was to investigate the splenic cell type(s) targeted by B(a)P resulting in suppression of humoral immunity. Separation-reconstitution studies along with in vitro sensitization techniques with several different antigens (sheep red blood cells (SRBC), dinitrophenyl-Ficoll (DNP-Ficoll), lipopolysaccharide (LPS)) were used to identify splenic target cells following exposure of mice to B(a)P (200 mg/kg/day, sc for 4 days). Findings indicate that in vitro plaque-forming cell (PFC) suppression was due to alterations in the adherent (macrophage) cell population. Exposure also suppressed the PFC response to the T-dependent antigen SRBC and the T-independent antigen DNP-Ficoll, but did not suppress the PFC response to the polyclonal antigen, LPS. These data suggest that B(a)P is targeting macrophages. PMID- 1412473 TI - Education Award. Dean E. Carter. PMID- 1412474 TI - 1992 Frank R. Blood Award. Donald Fox. PMID- 1412475 TI - 1992 Merit Award. W. Norman Aldridge. PMID- 1412476 TI - 1992 Achievement Award. Michael P. Holsapple. PMID- 1412477 TI - Advancing the understanding of multiple chemical sensitivity (MCS): overview and recommendations from an AOEC workshop. PMID- 1412478 TI - Diagnosis and treatment of hypersensitivity syndrome. PMID- 1412479 TI - Immunologic evaluation of chemically sensitive patients. PMID- 1412480 TI - Biologic and social factors in food sensitivities. PMID- 1412481 TI - Neuropsychophysiologic observations in patients presenting with environmental illness. PMID- 1412482 TI - The experience of the Yale Occupational and Environmental Medicine Clinics with multiple chemical sensitivities, 1986-1991. PMID- 1412483 TI - Chronic fatigue syndrome. PMID- 1412484 TI - Research strategies for investigating multiple chemical sensitivity. PMID- 1412485 TI - Possible models for multiple chemical sensitivity: conceptual issues and role of the limbic system. AB - Conceivably, chemicals contacting olfactory nerve projections in the nose could either be transported into or relay electrical signals to the limbic region, leading to a vast array of symptoms. Likewise, thought processes and mood states may trigger or interrupt pre-existing limbic activity. At present, however, no evidence suggests that limbic activity triggered by environmental exposures can be entirely overcome by psychologic interventions. One important ramification of a limbic hypothesis, if true, is that no convenient biologic marker for multiple chemical sensitivity may exist at the present time. Ten years from now, we may finally confirm the existence of multiple chemical sensitivities (by careful, blinded challenges) but still have no single mechanism to explain it; that is, after all avenues of biochemical and immunologic inquiry have been exhausted, no single cause or marker for this disorder may be apparent. The theory that adaptation plays a role in MCS is based on the observed responses of patients in a deadapted state who have been housed in an environmental unit. Although adaptation is only an observation at this time, not a mechanism, biologic limits might regulate how much an organism can adapt. Such limits could be highly individual and vary by orders of magnitude. Certainly adaptation occurs at all levels of biologic systems, from enzyme systems to cells, tissues, organs, and even behavior (Fregly, 1969). Theoretically, a major insult or the accumulation of lower-level injuries within these systems could lead to a kind of "overload" or "saturation" effect with respect to adaptive capacity. This might cause an individual to have environmental responses, which, instead of being flexible and fluid, would become fragile and overly responsive. Many MCS patients report that years, and in some cases decades, after the onset of their problems, they have recovered only a portion of their former energies and tolerance for their environment. Their descriptions seem to suggest the loss of an intangible capacity to adapt, parts of which may be temporary and recoverable and other parts of which may not. Perhaps our patients have been telling us the diagnosis. PMID- 1412486 TI - Multiple chemical sensitivities and the immune system. PMID- 1412487 TI - History and clinical presentation of the chemically sensitive patient. AB - Although no one has all the answers to the mystery of chemical sensitivity, the reality of this condition, most recently called multiple chemical sensitivities, is not in doubt. Evidence is increasing of its possible physiologic mechanisms, which will be discussed later in this volume. From the evidence and from personal and professional experience, the author believes that chemical sensitivity is not a diagnosis of exclusion, and that fixed-name diseases may have environmental triggers or complicating factors (Rea, 1990b). With appropriate preparation and environmental controls, MCS can be investigated and diagnosed in a scientific and reproducible manner. PMID- 1412488 TI - Is there evidence of an immunologic basis for multiple chemical sensitivity? PMID- 1412489 TI - Multiple chemical sensitivity: a respiratory disorder? PMID- 1412490 TI - Models of multiple chemical sensitivities (MCS) syndrome: using empirical data (especially interview data) to focus investigations. PMID- 1412491 TI - Acquired intolerance to solvents following pesticide/solvent exposure in a building: a new group of workers at risk for multiple chemical sensitivities? PMID- 1412492 TI - Epidemic multiple chemical sensitivity in an industrial setting. PMID- 1412493 TI - Development of multiple chemical sensitivity after an outbreak of sick-building syndrome. AB - Investigation of this outbreak raises some important points for future research. Although for various reasons the case ascertainment for MCS was not complete, the three MCS patients described here all had preexisting conditions that may have put them at risk. In addition, one person among the 20 described had chronic fatigue syndrome but did not develop MCS. Many of the persons described here continue to have ongoing complaints that are not MCS. Significant exacerbation of preexisting allergic disease and new onset of asthma occurred among those patients. As a group, they did not recover completely after the outbreak; several are no longer working in the building but in alternative work spaces. An important distinction should be made between individuals who met the definition used here for MCS and others who had significant exacerbation of some better defined illness brought on by building conditions. New onset of MCS was a partial but not complete explanation of the clinical course for this group of 20 persons. PMID- 1412494 TI - A survey of AOEC physician practices and attitudes regarding multiple chemical sensitivity. PMID- 1412495 TI - Multiple chemical sensitivity: treatment and followup with avoidance and control of chemical exposures. AB - Reducing unnecessary chemical exposures, particularly pesticides and other petrochemicals, shows promise for reducing illness episodes in the chemically sensitive. Because similar types of exposures have been associated with the onset of chemical sensitivity, such precautions could have wider preventive value for the rest of society as well. Many uses of chemicals have dubious social benefits, and reduced use should be achievable. The chemical industry will likely bitterly contest the reduced use of chemicals because it stands to lose substantial sales. Compensation and liability insurance carriers also stand to lose if the environment is found problematic, rather than individual psychology, for example. Professionals should also recognize conflicts of interest for the chemical and insurance industries by openly acknowledging funding sources for research. The author believes that research on chemical sensitivity that blames the psyche of the victim rather than the chemical will more likely be funded by the insurance or chemical industry than will other research. Study designs should be developed in an atmosphere removed from financial conflicts of interest. This means a substantially larger role for government funding of research on chemical sensitivity to avoid biasing the knowledge base by financially interested parties. The time is critical for government funding of research on chemical sensitivity because the illness is being defined and characterized. If preliminary research is flawed by improper design and focus, our understanding of the problem could be delayed for years. PMID- 1412496 TI - Treatment options in multiple chemical sensitivity. AB - The essential features of treatment for chemical sensitivity are: 1) Encouraging the provision of clean air, food, water, and surroundings. 2) Identifying substances to which the patient is sensitive, with subsequent a) enhanced avoidance, or b) specific immunotherapy to reduce the patient's reactivity to those substances. 3) Assessing and enhancing the patient's nutritional status to maximize the body's ability to detoxify and to minimize the free-radical production and oxidative stress of xenobiotics. 4) Addressing concurrent problems such as infections, immunosuppression, and other medical conditions in an appropriate fashion. 5) Evaluating the patient's psychologic status and addressing any social and emotional problems in a compassionate manner. The author believes that multiple chemical sensitivity is a real condition with documented physiologic abnormalities. It is not a functional or psychologic illness or a belief system of the patient. Second, this condition is diagnosable and treatable by various means. These treatment options not only make common sense but usually result in significant improvement for these unfortunate patients, who deserve the very best efforts of their health care providers. PMID- 1412497 TI - Multiple chemical sensitivities: a practicing clinician's point of view. Clinical and immunologic research findings. AB - The multiple chemical sensitivities syndrome is a symptom complex characterized by emotional depression, short-term memory loss, acquired intolerance to environmental agents such as aerosolized petrochemicals and foods, and alteration in metabolic rate associated with increased body mass. This syndrome can be caused by multiple etiologic agents. With careful evaluation, it is rare that a causal agent can not be identified in this syndrome. Our treatment regimens include combinations of diet and environment control as well as antiviral, antifungal, and immune modulator therapy. We find that the majority of patients can, through time and appropriate treatment, be restored to a normal and productive lives. PMID- 1412498 TI - Effects of amiodarone administration during lactation in Fischer-344 rats. AB - The antiarrhythmic drug, amiodarone, was administered (35 mg/kg, p.o.) once daily to lactating Fischer-344 rats for either the first 7 days of lactation, the first 14 days of lactation, or for the full 24-day lactational period. Treatment with amiodarone resulted in a decrease in maternal weight gain compared to pair-fed vehicle-treated controls, however, neonatal weight gain was not affected. The concentration of amiodarone in the maternal milk was approx. 6-fold higher than its primary metabolite, desethylamiodarone. Plasma levels of amiodarone and desethylamiodarone were higher in maternal rats compared to neonates. Both amiodarone and desethylamiodarone were distributed to neonatal tissues through lactational transfer. The levels of desethylamiodarone were higher in neonatal lung compared to liver at all treatment times. They were also elevated above amiodarone in neonatal lung at all treatment times. The amiodarone levels in neonatal lung and liver were similar. PMID- 1412499 TI - Studies of the amplification of carbaryl toxicity by various oximes. AB - The administration of 2-pyridine aldoxime methyl chloride (2-PAM Cl) is a standard part of the regimen for treatment of human overexposure to many organophosphorus pesticides and nerve agents. However, some literature references indicate that poisoning by carbaryl (1-naphthyl N-methyl carbamate), an insecticide in everyday use, is aggravated by the administration of 2-PAM Cl. This effect has been reported in the mouse, rat, dog and man. We have found that the inhibition of both eel acetylcholinesterase (eel AChE, EC 3.1.1.7) and human serum cholinesterase (human BuChE, EC 3.1.1.8) by carbaryl was enhanced by several oximes. Based on 95% confidence limits the rank order of potentiation with eel AChE was TMB-4 = Toxogonin > HS-6 = HI-6 > 2-PAM Cl. By the same criterion, the rank order of potentiation with human BuChE was TMB-4 > Toxogonin > HS-6 = 2-PAM Cl. Carbaryl-challenged mice also reflected a potentiation since TMB-4 exacerbated the toxicity more than 2-PAM Cl. Our hypothesis is that certain oximes act as allosteric effectors of cholinesterases in carbaryl poisoning, resulting in enhanced inhibition rates and potentiation of carbaryl toxicity. PMID- 1412501 TI - Effect of preperfusion of ascending concentrations of lead on digoxin-induced cardiac arrest in isolated frog heart. AB - The present work investigated the effect of preperfusion of ascending concentrations of lead acetate (LA) (10(-9), 10(-7) and 10(-5) M) on digoxin (DGN) cardiotoxicity in isolated frog heart, in order to look for any consequent variations in its lead-induced potentiation. The DGN perfusion time(s) and DGN exposure (micrograms DGN/10 mg heart weight) for, and myocardial DGN level (ng DGN/g wet tissue) at, cardiac arrest were the parameters evaluated so as to assess cardiotoxicity. Both sodium acetate and LA (10(-7) M) preperfusion led to a diminution in cardiac rate at 10 min of DGN perfusion without altering the contractility compared to the DGN alone group. With regard to DGN perfusion time for cardiac arrest, preperfusion of ascending concentrations of LA induced a corresponding decrease which was statistically significant (P < 0.05). On the other hand, in the experimental group that received preperfusion of 10(-9) M LA, the DGN exposure for cardiac arrest was not significantly different from that of the control, whereas in the 10(-7) and 10(-5) M groups, it was significantly lower (P < 0.05). In the experimental group that received preperfusion of 10(-7) M LA, the significant reduction in DGN perfusion time and DGN exposure was well corroborated by a diminution in the myocardial DGN level (4.01 +/- 0.17 ng/g wet tissue in comparison with the control value of 5.72 +/- 0.4 ng/g wet tissue, P < 0.05) at cardiac arrest. Taken together, these data reveal that with the preperfusion of LA in ascending concentrations, there is a relative increase in LA-induced potentiation of DGN cardiotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412500 TI - Dietary pyrrolizidine (Senecio) alkaloids and tissue distribution of copper and vitamin A in broiler chickens. AB - The effect of feeding a diet containing 5% tansy ragwort (TR) (Senecio jacobaea), a poisonous plant containing pyrrolizidine alkaloids (PA), on the blood and liver levels of copper, zinc, iron and vitamin A in broiler chicks was examined. Serum and liver copper and liver iron concentrations were increased in chicks fed a diet with 5% TR, while serum and liver zinc and vitamin A decreased. When PA were removed from the diet, partial restoration of normal serum vitamin A level occurred, indicating that the ability to mobilize liver vitamin A is not irreversibly inhibited by PA. The decline in serum vitamin A occurred by 8 days of TR feeding with a concurrent decline in growth rate. When chicks were fed a diet high in vitamin A (25,000 IU/kg), followed by a basal diet containing TR, serum vitamin A levels were significantly (P < 0.01) decreased, while liver vitamin A level increased. This indicates that mobilization of previously stored vitamin A from the liver is impaired by PA. Prior feeding of a high vitamin A level resulted in protective effects against PA toxicity, as assessed by histopathology. This study shows that a dietary source of PA modifies metabolism and tissue distribution of minerals and vitamin A. PMID- 1412502 TI - Morphological changes in the respiratory system of mice after inhalation of mosquito-coil smoke. AB - Male ICR mice were exposed to mosquito-coil smoke with d-allethrin or without d allethrin at airborne particles concentration of 1.27 mg/m3, 7 h/day, 7 days/week for 1, 3, 6, and 12 months. Additional groups of air exposure animals served as controls. At 1 month after exposure, the histopathological lesions included the loss of cilia, and the alteration of the alveolar pattern in the treated and the sham mice. Volume fractions of the type I and II cells were smaller (0.028 +/- 0.006, 0.044 +/- 0.002) in the treated group than those of the controls (0.049 +/ 0.008, 0.059 +/- 0.003). Fractions of the lumina of vessels and the vessel wall decreased in both the treated and the sham groups as compared to the control group. However, the volume fraction of alveolar air space increased significantly in both treated and sham groups as compared to the controls (0.619 +/- 0.022, 0.685 +/- 0.018 vs. 0.507 +/- 0.025). After 3- and 6-months exposure, the lesions observed in the trachea persisted. The intercellular fibrosis in the lung was increased in both the treated and sham groups at 6 months and became more severe at the later stages. At 12-months exposure, an increase in vascularity of the alveolar wall was observed and fine granular debris was frequently present in the alveolar space. The fraction volumes of the type II cells in the treated group and the type I cells in the sham group were significantly increased (0.059 +/- 0.010, 0.042 +/- 0.003) compared with those of the controls (0.038 +/- 0.008, 0.033 +/- 0.003). However, the fraction volume of air space and vessel lumen were not different among the three groups. Finally, there were no differences in the morphologic appearance of the airways and the lung periphery between the treated and the sham-exposed animals. PMID- 1412503 TI - Combined effect of cadmium and nickel on rat hepatic monooxygenases: possible stimulation of certain cytochrome P-450 isozymes. AB - When male rats were given either a single dose of cadmium (3.58 mg CdCl2.6H2O/kg, i.p.) 72 h prior to sacrifice or a single dose of nickel (59.5 mg NiCl2.6H2O/kg, s.c.) 16 h prior to sacrifice, the activities of ethylmorphine N-demethylase, aminopyrine N-demethylase and aniline 4-hydroxylase, and the levels of cytochrome P-450 and microsomal heme were significantly decreased. Cadmium decreased the cytochrome b5 level significantly, whereas it did not alter the NADPH-cytochrome c reductase activity significantly. In contrast, Ni did not alter the cytochrome b5 level significantly but decreased the NADPH-cytochrome c reductase activity significantly. For the combined treatment, animals received the single dose of nickel 56 h after the single dose of cadmium and then they were killed 16 h later. In these animals ethylmorphine N-demethylase, aminopyrine N-demethylase and NADPH-cytochrome c reductase activities and cytochromes P-450 and b5 levels increased significantly as compared to those of controls, whereas aniline 4 hydroxylase activity and microsomal heme level remained unaltered. In concordance with the increase in the enzyme activities, certain P-450 protein bands were observed to be elevated when studied on SDS-polyacrylamide gel electrophoresis. Furthermore, when the monooxygenase activities and SDS-polyacrylamide gel electrophoresis profiles of combined metal-treated animals were compared with those of the animals treated with classic inducers such as phenobarbital (75 mg/kg i.p., 72, 48 and 24 h prior to sacrifice) and 3-methylcholanthrene (20 mg/kg i.p., 72, 48 and 24 h prior to sacrifice), the combination of metals seemed to have tendency to stimulate certain phenobarbital and 3-methylcholanthrene inducible cytochrome P-450 isozymes. PMID- 1412504 TI - The metabolism of 1,3-dinitrobenzene by rat testicular subcellular fractions. AB - The metabolism of 1,3-dinitrobenzene by rat testicular subcellular fractions (microsomes, cytosol or 9000 x g supernatant (S-9)) was studied. The effects of NADPH, oxygen, glutathione (GSH) and carbon monoxide upon the rate of metabolism were determined. Three metabolites were identified, and characterised as 3 nitrosonitrobenzene, 3-nitrophenylhydroxylamine and 3-nitroaniline by co chromatography with authentic standards. These findings indicate the presence of an inherent enzyme system capable of facilitating nitro-reduction in the testes. The implications of these findings to the mechanism of 1,3-DNB-induced testicular toxicity are discussed. PMID- 1412505 TI - Carcinogenicity assessment of lonidamine by dietary administration to Sprague Dawley rats. AB - Following chronic dietary administration of 20, 60 and 180 mg/kg per day of lonidamine for 2 years to groups of Sprague-Dawley rats, treatment-related non tumour findings seen microscopically included the following: atrophy of the testis with associated changes in epididymis and pituitary at all dosages; neuropathy in the sciatic nerve accompanied by skeletal muscle atrophy which was dose-related, particularly in male animals. Neither the incidence of tumour bearing animals, nor the spectrum of tumours seen, was significantly changed. In the females given 180 mg/kg per day an overall reduction in tumour incidence was noted, which was reflected in a significant reduction (P < 0.001) in mammary tumours. PMID- 1412506 TI - Subchronic toxicity study of peppermint oil in rats. AB - Peppermint oil was given p.o. to four groups of 28 rats at dosage levels of 0, 10, 40, and 100 mg/kg body wt. per day for 90 days. At the highest dose histopathological changes consisting of cyst-like spaces scattered in the white matter of cerebellum were seen. No other signs of encephalopathy were observed. Nephropathy was seen in the male rats in the highest dose group. A no-observed adverse-effect level of 40 mg/kg body wt. per day was determined. PMID- 1412507 TI - Covalent binding of ethylene dibromide and its metabolites to albumin. AB - The present study was undertaken to determine covalent binding of [1,2 14C]ethylene dibromide (EDB) to albumin under in vivo and in vitro conditions. For the in vivo covalent binding, 25 mg/kg body weight of [1,2-14C]EDB was given daily to male rats for 12 consecutive days and the animals were sacrificed at 24 h following the last dose. Blood was withdrawn from inferior vena cava in heparinized tubes and plasma was separated, dialyzed against ice-cold 10 mM phosphate buffer (pH 7.4) and then subjected to size-exclusion high-performance liquid chromatography (SE-HPLC). A major radioactive peak eluted at an elution volume corresponding to 65,000 dalton molecular mass was found to be associated to albumin at a level of 0.14 nmol equivalent EDB/mg protein. For the in vitro covalent binding, human plasma or purified albumin was incubated with [1,2 14C]EDB in the presence of phenobarbital-treated rat liver microsomes and NADPH generating system for 2 h at 37 degrees C. The 100,000 x g supernatant of the incubation mixture was dialyzed extensively and analyzed as described for the in vivo studies. Approximately 0.28 nmol equivalent EDB/mg protein was found to be associated to albumin (about 2-fold higher than the in vivo binding). Binding of 14C-label to albumin under in vivo and in vitro conditions was further supported by the affinity chromatography of albumin fraction isolated by SE-HPLC. Reversed phase HPLC analysis of pronase digest of the albumin obtained from in vitro studies indicated formation of several amino acid adducts of EDB and/or its metabolites. Structure elucidation of such amino acid adducts will be helpful in developing a relatively non-invasive method of measuring the EDB exposure. PMID- 1412508 TI - Co-exposure to gasoline vapor decreases benzene metabolism in Fischer-344 rats. AB - The metabolic interactions of benzene and gasoline vapor were investigated in male Fischer-344 rats. A closed chamber gas-uptake exposure system was used to obtain inhalation uptake curves for benzene alone and benzene in the presence of gasoline vapor. Exposure to benzene as a component of gasoline vapor resulted in a decrease of benzene metabolism. A physiologically based pharmacokinetic model of benzene metabolism was used to quantitatively determine the extent of the inhibitory effect of gasoline vapor on benzene metabolism. This observed inhibitory effect cannot be accounted for by the presence of toluene in gasoline vapor. PMID- 1412509 TI - Inhibition of human hepatic glutathione S-transferase isozymes by ethacrynic acid and its metabolites. AB - The comparative inhibition of ethacrynic acid (EA) and its known metabolites against glutathione S-transferase (GST) was investigated using human livers procured from kidney donors. EA and all three metabolites of EA had an inhibitory effect against conjugation between 1-chloro-2,4-dinitrobenzene (CDNB) and glutathione (GSH). The GSH adduct of EA (EA-GSH) was the most potent inhibitor of GSTs; EA-GSH was approximately one order of magnitude more potent than the parent EA, while L-cysteine conjugate of EA (EA-cysteine) and N-acetyl-L-cysteine conjugate of EA (EA-mercapturate) were approximately two orders of magnitude less potent than the parent EA. Further metabolism of EA-GSH conjugate is suggested to be a detoxification process in terms of GST activities. PMID- 1412510 TI - In vitro hydrolysis of methyl acetate, a limitation in application of head-space gas-chromatography in biological monitoring of exposure. AB - Stoichiometric conversion of methyl acetate to methanol in vitro was detected when methyl acetate was incubated with blood for 2 to 8 h. The velocity of the reaction was so fast that almost all of methyl acetate disappeared in 8 h. The methanol formation was further confirmed by means of gas-chromatography-mass spectrometry. The capacity to hydrolyze methyl acetate was evenly distributed in cellular and noncellular fractions of blood, but not in urine. The significance of the observation is discussed in relation to biological monitoring of exposure to industrial ester solvents by means of head-space gas-chromatography of blood samples. PMID- 1412511 TI - Benzo[a]pyrene and nicotine impair epidermal growth factor mediated cellular functions of buccal mucosa. AB - This study investigated the effect of two major ingredients in cigarette smoke, benzo[a]pyrene (BP) and nicotine, on epidermal growth factor (EGF) receptor binding and EGF-mediated cellular functions in rat buccal mucosa. Rat buccal tissue was incubated in DMEM in the absence (control) and presence of 10 microM BP or nicotine for 2.5 h at 25 degrees C. There were no significant differences in [125I]EGF binding to the buccal mucosal membranes between the control and treatment groups. Protein tyrosine kinase assay showed that EGF stimulated phosphorylation of a 170-kDa protein band in the controls, but not in the BP- and nicotine-treated samples. The basal [3H]thymidine incorporations were not significantly different between the groups. Nevertheless, addition of 5 nM EGF increased [3H]thymidine incorporation by 22% in the control, but not in the BP- or nicotine-treated group. The results demonstrate that BP and nicotine change the buccal mucosal functions associated with alteration of EGF receptor. PMID- 1412512 TI - Endocrine pancreas in the postnatal offspring of alloxan diabetic rats. AB - This study was conducted to investigate the morphological changes in the postnatal pancreatic islets in offspring of diabetic rats. Diabetes was induced in female Sprague Dawley rats by intravenous injection of alloxan (40 mg/kg). After 1 week, rats with blood sugar above 270 mg% were bred and watched until spontaneous delivery occurred. Litters in the following age groups were sacrificed by decapitation, 0, 8, 24, 72 and 168 h, and compared with their controls. Blood sugar levels were significantly higher in the neonates of diabetic mothers immediately after delivery compared to the control, then became normal after 8 h. Islets of the offspring of the diabetics at birth showed weak positive staining for insulin using immunocytochemical techniques. By 72 h some cells showed immunopositive staining similar to the control, while at 168 h all the beta (B) cells were stained normally. Beta cells of the islets from the diabetic series at birth were almost completely degranulated except for scattered granules toward the periphery. Their cytoplasm exhibited glycogen and lipid accumulations. Cells also showed signs of hyperfunction in the form of an extensive endoplasmic reticulum and well-developed Golgi complex with distended Golgi cisternae. At 8 h postnatally the population of pale secretory granules was markedly increased. The changes described at birth persisted at 24 h and, to a lesser extent, 72 h after delivery. At the age of 1 week, the beta cells appeared to be normal. PMID- 1412513 TI - Rates of ethyl acrylate binding to glutathione and protein. AB - Ethyl acrylate is a monomer used extensively in polymer manufacturing. Although ethyl acrylate is toxic at high concentrations, it is metabolized and detoxified rapidly at low concentrations. In the current studies, in vitro experiments have demonstrated that [14C]ethyl acrylate reacts with both glutathione (GSH) and protein to give either [14C]3-(glutathion-S-yl)ethylpropionate or covalently bound protein adducts, respectively. The second-order rate constant for [14C]ethyl acrylate conjugation with GSH was determined by quantification of [14C]3-(glutathion-S-yl)ethylpropionate using an HPLC system equipped with a flow through radioactive detector. The rate constant for conjugation was 32.8 M-1 min 1. Additionally, the apparent second-order rate constants were determined for [14C]ethyl acrylate binding to the protein fraction of 14 whole tissue homogenates. Estimation of total protein binding sites was performed by reacting tissue homogenates with high concentrations of [14C]ethyl acrylate, while rates of binding were determined by reacting tissue homogenates with 200 microM [14C]ethyl acrylate at 37 degrees C for various periods of time. Apparent second order rate constants for ethyl acrylate binding to protein homogenates were similar to that observed for GSH reacting with ethyl acrylate. The role of GSH transferase in catalyzing 3-(glutathion-S-yl)ethylpropionate formation also was evaluated with whole tissue homogenates. In most tissues, the GSH-transferases poorly catalyzed the conjugation reaction. However, a significant increase in 3 (glutathion-S-yl)ethylpropionate formation was observed with liver homogenate. PMID- 1412514 TI - Inhibition of acetaminophen hepatotoxicity by acetaldehyde in the rat. AB - Since we have observed that acetaldehyde, an oxidative metabolite of ethanol, inhibits acetaminophen activation in rat liver microsomes, the in vivo effect of acetaldehyde on acetaminophen hepatotoxicity was tested. In vivo experiments in 3 methylcholanthrene-pretreated male Sprague-Dawley rats showed that administration of cyanamide (20 mg/kg, i.p.) and acetaldehyde (600 mg/kg, s.c.) given 3 and 1 h, respectively, prior to acetaminophen (500 mg/kg, i.p.) but not cyanamide alone prevented acetaminophen hepatotoxicity as assessed by serum transaminases and histology. Acetaldehyde may partly be responsible for the inhibitory effect of ethanol on acetaminophen hepatotoxicity. PMID- 1412515 TI - Mechanism of the increase in lipid peroxide induced by cisplatin in the kidneys of rats. AB - To clarify the mechanism where by cisplatin induces increases in lipid peroxide, we examined the effects of antioxidants on changes in the activity of lipid peroxidation protecting enzymes in the kidneys of rats after cisplatin administration. alpha-Tocopherol and glutathione (GSH) significantly depressed lipid peroxidation in the kidneys of cisplatin-treated rats on the 4th day after cisplatin administration, and GSH depressed the increases in blood urea nitrogen levels induced by cisplatin. Thus, GSH appeared to reduce cisplatin-induced nephrotoxicity. However, alpha-tocopherol and GSH had no effect on the significant decrease in the activity of lipid peroxidation protecting enzymes induced in the kidney after cisplatin treatment. These results showed that lipid peroxide produced by cisplatin had no effect on these enzymes, suggesting that the increases of lipid peroxide were a result of the cisplatin-induced reduction in the activity of these enzymes. PMID- 1412516 TI - Endrin-induced production of nitric oxide by rat peritoneal macrophages. AB - The effect of oral endrin administration to rats on the production of nitric oxide (NO) by peritoneal macrophages was investigated. Nitric oxide formation was measured as nitrite. Endrin (4.5 mg/kg) enhanced the secretion of NO by approx. 300%. The effect of endrin on NO formation was both dose- and time-dependent. Ellagic acid, which has been shown to be a potent antioxidant, inhibited the elevation of NO production induced by endrin. These results suggest that the toxicity of endrin may at least in part be due to the production of an oxidative stress. PMID- 1412517 TI - Wy-14,643 stimulates hepatic protein kinase C activity. AB - The mechanism by which hypolipidemic drugs and industrial plasticizers cause hepatic tumors in rodents remains unknown. Protein kinase C is elevated during hepatic cell turnover, and sustained cellular replication has been shown to correlate with an increase in hepatic tumors. Therefore, the effect of [4-chloro 6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) on protein kinase C activity was examined. Female Sprague-Dawley rats were given 100 mg/kg Wy-14,643 in olive oil (i.g.), while control rats received equal volumes of oil vehicle. After 24 h, the activity of protein kinase C was estimated in isolated hepatic fractions by measuring the binding of 3H-phorbol-12,13-dibutyrate, a specific ligand for protein kinase C. Administration of Wy-14,643 significantly increased protein kinase C activity nearly 2-fold in microsomal fractions. Thus, it is possible that Wy-14,643 increases cell proliferation and causes tumors by mechanisms involving protein kinase C. PMID- 1412518 TI - Effects of metyrapone and L-tryptophan administration on eosinophils in peripheral blood of mouse. PMID- 1412519 TI - Criterion of reliability as the function of variability and significance of biological parameters. AB - A differentiated approach to the choice of criterion of reliability in toxicological studies is recommended. This approach is based on quantitative assessment of variability of biological parameters using the variation coefficient. All biological parameters are classified into rigid, flexible and high-flexible ones. The establishment of the biological significance of various parameters and assessment of the degree of their deviation allows the detection of prepathological changes in the body state, this being of importance for a more accurate LOAEL and NOAEL determination. PMID- 1412520 TI - Protective effect of copper against cadmium cytotoxicity on cultured vascular endothelial cells. AB - We investigated the effect of copper on cadmium-induced cytotoxicity on vascular endothelial cells from bovine aorta in a culture system. Cytotoxicity was evaluated by the [3H]adenine release assay and the histological observation. After a 24-h incubation, cadmium exhibited a significant cytotoxicity on confluent cultures of endothelial cells in a dose-dependent manner, while copper only slightly did after a 24-h incubation. It was found that copper (5 microM) significantly decreased cadmium (1 and 2 microM) cytotoxicity; histologically, formation of de-endothelialized areas in the cell layer caused by cadmium was reduced by copper. The accumulation of cadmium in the cell layer was significantly decreased by copper; however, that of copper was unaffected by cadmium. It was therefore suggested that copper significantly protects cadmium induced cytotoxicity on cultured endothelial cells primarily through decreasing the cellular cadmium accumulation. PMID- 1412522 TI - Detection of sulphur-conjugated pyrrolic metabolites in blood and fresh or fixed liver tissue from rats given a variety of toxic pyrrolizidine alkaloids. AB - Rats were given single injections of hepatotoxic pyrrolizidine alkaloids and killed after 30 h. Sulphur-bound pyrrolic metabolites from the alkaloids in samples of their blood or liver tissue were converted to extractable ethyl ethers of low molecular weight for detection and identification using TLC, HPLC or GC MS. Liver samples were also preserved as an acetone-washed powder or in formalin based fixative before being later subjected to similar analyses. S-Bound pyrrolic metabolites were identified in samples from rats given all the types of alkaloid tested, which included mono-esters (heliotrine, indicine), a diester (lasiocarpine), and macrocyclic diesters (retrorsine, senecionine). The pattern of pyrrolic metabolites from the crotanecine-based alkaloid anacrotine differed and could be distinguished from retronecine- or heliotridine-based alkaloids. Whereas the alkaloids tested ranged widely in toxicity, single doses of 0.25 x acute LD50 or more led to detectable metabolites. Liver pyrroles remained detectable in fixed or powdered samples preserved for long periods. Similar tests on rats given monocrotaline continuously in their drinking water (20 mg/l) led to detectable pyrroles in blood after 12 days (total intake approx. 27 mg/kg) and in liver after 25 days. The metabolites remained detectable in rats killed 17 days after the alkaloid exposure was discontinued. The simple procedures described are applicable to the diagnosis of pyrrolizidine alkaloid exposure in livestock, using fresh or dried blood or fresh or preserved liver samples. They bring to pyrrolizidine toxicology for the first time the capability to demonstrate chemically that livestock (or people) have been exposed to these alkaloids many days or weeks previously. PMID- 1412521 TI - Mutagenicity of nitroxyl compounds: structure-activity relationships. AB - Three piperidinoxyl radicals were found to be directly mutagenic in Salmonella typhimurium TA 100, one pyrrolidinoxyl compound had weaker activity, and two other pyrrolidinoxyl derivatives did not produce an increase of the spontaneous revertants. The tester strain TA 100 was selected in preliminary tests for its higher sensitivity compared to TA 98 and TA 102. The mutagenic activity of the three active compounds was abolished by partial reduction with ascorbic acid, suggesting that the mutagenicity was linked to the free radical nature of these compounds, and reduced in the presence of a cofactor supplemented rat liver subcellular fraction. The mutagenicity of the tested compounds was correlated to the resistance of the nitroxyl spin labels to reduction: the more reactive radicals were found to possess higher mutagenic activity. PMID- 1412524 TI - Pentamidine isethionate is negative in tests for microbial mutagenicity and chromosomal breakage in vitro. AB - Pentamidine isethionate, a drug used for the treatment of Pneumocystis carinii pneumonia in AIDS patients, was assayed for mutagenicity in five strains of Salmonella typhimurium and for clastogenicity and mutagen-induced chromosomal breakage in five human lymphoblastoid cell lines. The mutagenicity assay employed both repair-deficient and repair-positive strains without and with the addition of rat liver S-9. There was no indication of a mutagenic response in any of the strains of Salmonella. Chromosomal breakage was measured in lymphoblastoid cell lines, both in the absence and presence of bleomycin. Following 2, 5 and 24 h of treatment, pentamidine alone did not induce clastogenicity, nor was there an increase in chromosomal breakage when the cell lines were treated with bleomycin simultaneously with, or 22 h prior to, the addition of pentamidine. From these data it can be concluded that pentamidine is not mutagenic or clastogenic in the two assays employed in this study. PMID- 1412523 TI - Sex differences in the bioavailability of soil-adsorbed m-xylene in orally exposed rats. AB - The bioavailability of soil-adsorbed m-xylene was assessed in male and female rats gavaged with an aqueous suspension of 14C-m-xylene alone or adsorbed to sandy or clay soil. Sex-related differences were observed in the rate and the amount of m-xylene-derived radioactivity absorbed and excreted in the presence of the soils. A higher peak plasma concentration of radioactivity was observed in females following treatment with sandy soil-adsorbed m-xylene. Further, sandy and clay soil-adsorbed chemicals demonstrated significantly longer absorption half lives (t1/2), while sandy soil produced a shorter elimination t1/2 vs. m-xylene alone in female rats. Increased bioavailability of sandy soil-adsorbed m-xylene in females was evidenced by a significantly increased area under the plasma concentration time curve (AUC). Neither of the soils altered the maximum plasma concentration, the rate at which xylene-derived radioactivity was absorbed or eliminated, or the AUC in male rats. Fat contained the highest tissue concentration of xylene-derived radioactivity in all treatment groups of both sexes. Further, in all male and female treatment groups m-xylene was primarily metabolized and excreted in urine with methyl hippuric acid identified as the main urinary metabolite. Sandy soil slightly delayed urinary excretion in females while both soils increased expired air excretion in males compared to m-xylene alone. Methylhippuric acid was the main urinary metabolite in all groups. PMID- 1412525 TI - Kinetics of aluminum in rats. IV: Blood and cerebrospinal fluid kinetics. AB - Aluminum causes central nervous system (CNS) toxicities in both humans and various animal species. Although blood aluminum concentrations are monitored in the clinic, very little is known regarding the relationship between such concentrations and corresponding CNS aluminum content. As a first step in that direction, this study was undertaken to simultaneously determine blood and CSF kinetics of this element. Following intravenous injection of aluminum (1 mg/kg), there was a rapid (within 30 min, post injection) increase in CSF aluminum; peak concentrations (38-45 ng/ml) were achieved between 2-3 h. While peak blood aluminum concentrations increased about 58-fold from the pre-dose value (from 256 +/- 120 to 14,730 +/- 388 ng/ml), corresponding increases in CSF aluminum were only about 20-fold. Blood and CSF aluminum concentrations declined monoexponentially with half-lives of 2.77 and 3.45 h, respectively (P < 0.05). Results from these showed that blood and CSF compartments achieve equilibrium and indicated the feasibility of determining brain aluminum content using blood concentrations. PMID- 1412526 TI - Stability of allylthiocyanate and allylisothiocyanate in bovine ruminal fluid. AB - The rate of allylisothiocyanate (AITC) disappearance in bovine rumen fluid in vitro was 50-fold greater than the rate for allylthiocyanate (ATC). The results indicate that unlike AITC, ATC is more likely to be absorbed from the forestomachs and possible transferred to milk. PMID- 1412527 TI - Glutathione and tissue amino acid responses to light-exposed parenteral nutrients. AB - Effects of infusion of light-exposed (+L) or light-protected (-L) total parenteral nutrition solutions were investigated in rats. The parenteral infusions were carried out for 7 days through jugular cannulas in freely moving rats in metabolic cages. Plasma tyrosine and citrulline, hepatic methionine, valine, isoleucine, leucine and tyrosine, and biliary cystathionine were significantly greater in the -L than +L rats, whereas biliary arginine was significantly lower in the -L compared to +L rats. Bile flow, biliary inorganic phosphate and glucose were significantly lower, whereas biliary total glutathione (GSH+GSSG) was significantly greater in the -L compared to +L animals. These data suggest adverse effects on hepatobiliary function due to light exposure of parenteral nutrients. The endogenous markers used suggest that tight junction permeability, bile acid-independent flow, glutathione and amino acid homeostasis are altered by light exposure and that these changes can be minimized by light protection. The mechanisms involved in the induction of these changes need to be elucidated. The role of light exposure of parenteral nutrients during routine clinical use in the induction of hepatic dysfunction, a common metabolic complication of parenteral nutrition, needs to be considered. PMID- 1412528 TI - Dietary restriction decreases thiobarbituric acid-reactive substances generation in the small intestine and in the liver of young rats. AB - This study investigated the influence of dietary restriction on thiobarbituric acid-reactive substances (TBARS) contents and on the intracellular antioxidant defence system in the small intestine or liver of young rats. Four weeks of diet restriction (-40%) lowered the TBARS level in both organs. No variations were found for the superoxide dismutase and catalase activities; only liver seleno dependent glutathione peroxidase was enhanced by the restriction. The protection appeared more marked in the intestine than in the liver, and would be dependent on glutathione concentration. PMID- 1412529 TI - Clinical expression of organophosphate-induced delayed polyneuropathy in rats. AB - Single doses of certain organophosphates (OP), such as dibutyl-2,2-dichlorovinyl phosphate (DBDCVP) cause organophosphate-induced delayed polyneuropathy (OPIDP) in hens. Clinical effects correlate with inhibition of neuropathy target esterase (NTE) which is considered the target for this toxicity. Pre-treatment with non neuropathic NTE inhibitors, such as phenylmethanesulfonyl fluoride (PMSF), protects from OPIDP. However, when given after OPs, these compounds promote OPIDP. Chicks are relatively resistant to OPIDP despite high NTE inhibition. It has also always been reported that rats represent a species which is resistant to OPIDP and that they might develop morphological but not clinical signs of OPIDP. We report here that clinical OPIDP can be produced in 3.5- and 6-month-old rats by DBDCVP (5 mg/kg s.c.) and that it correlates with high (> 90%) NTE inhibition. When PMSF (120 mg/kg s.c. x 2) was given after DBDCVP, OPIDP was promoted. Pretreatment with PMSF protected from OPIDP. We conclude that resistance to OPIDP in the rat is age-related, as it is in the hen. PMID- 1412530 TI - [The morphological changes in the periodontal tissues of outbred white rats during ontogeny]. AB - Morphologic studies, carried out by three methods, by van Gieson's, Schmorl's methods, and with the use of 0.1% solution of safranin T, have revealed heretofore unknown structures lying beyond the tooth rudiment of white noninbred rats and disappearing in the course of ontogenesis. The mechanism of the formation of autonomic circulation of the dental follicle, unrelated to the animal body, has been shown. Dental follicular tissues were found grown together with the gingival epithelium and they ruptured during tooth eruption. PMID- 1412531 TI - [The effect of different vacuum therapy regimens on protein and mineral metabolism in periodontal tissues]. AB - Radionuclide label was used to study the effects of various vacuum therapy schemes on the protein and mineral metabolism in periodontal tissues. Vacuum therapy was found to normalize Ca, P, and protein metabolism in spontaneous atrophy of the alveolar processes in white rats. Focal dosed vacuum was found the most effective. These data will be used to develop a complex of measures to prevent atrophies of the maxillary alveolar processes. PMID- 1412532 TI - [Alkaline and acid phosphatase activity in the dynamics of ectopic osteogenesis]. AB - Activities of marker enzymes of osteoblasts (alkaline phosphatase), osteoclasts (tartrate-resistant isoform of acid phosphatase), and macrophages (tartrate sensitive isoform of acid phosphatase) in bone tissue forming after osteoinduction on the basis of demineralized bone matrix were under study. Early (1 week) stages of osteosynthesis were characterized by low activity of alkaline phosphatase, acid phosphatase being represented by the tartrate-sensitive isoform. Two-three weeks later alkaline phosphatase activity grew and the tartrate-resistant isoform of acid phosphatase appeared. By the fourth-sixth weeks of osteogenesis alkaline phosphatase activity stabilized at a certain level and acid phosphatase activity still grew at the expense of the tartrate-resistant isoform. Conformity of the enzymologic data to changes in cellular populations in ectopic osteogenesis is discussed. PMID- 1412533 TI - [An experimental study of the effect of biopolymers on the course of an inflammatory process in the oral mucosa]. PMID- 1412534 TI - [Lipid peroxidation and the status of the basal membrane of the acinar cells in the minor salivary glands of patients with Sjogren's syndrome]. AB - Lipid peroxidation parameters were assessed from the levels of malonic dialdehyde, antioxidant activity from the blood and salivary total antioxidant activity, biopsy specimens of the minor salivary glands were examined by electron microscopy in 34 patients with Sjogren's disease. Both blood and salivary levels of malonic dialdehyde were found increased whereas total antioxidant activity lowered in these patients; destructive changes were detected in the acinar cells basal membranes. The authors suggest that spontaneous (because of insufficiency of antioxidant enzymic systems) lipid peroxidation reactions are responsible for these changes. PMID- 1412535 TI - [Mineral metabolism in orthotopic allografts preserved by different methods after their transplantation to a defect in the mandible]. PMID- 1412536 TI - [A method for assessing the efficacy of means for interdental space hygiene]. AB - A method for assessment of the efficacy of various means for maintenance of interdental space hygiene is suggested, based on measurement of the activity of acid producing oral microflora expressed through local pH-metry values. Three types of dental threads were under study. PMID- 1412537 TI - [Changes in the electric conductivity of the dentin during caries treatment]. AB - Dentin permeability at the bottom of carious cavities of 124 teeth was studied by electrometry. Dentin permeability was found to be higher in deep caries than in moderate-severe and higher in the teeth that had not been treated before than in those filled. Treatment of the cavities with potassium oxalate before filling helped rapidly and effectively lower the dentin permeability in order to prevent involvement of the pulp. PMID- 1412538 TI - [The ATPase content of the blood neutrophils and lymphocytes in patients with chronic periodontitis]. AB - Chronic periodontitis is associated with reduced immunologic reactivity of the body, that may present as disturbed status of the lymphocytes and neutrophils due to reduced activity of adenosine triphosphatases. Drug therapy of periodontitis, physiotherapy, oral hygiene, sodium chloride reducing diets are conductive to improvement of the clinical status of the periodontium and to recovery of ATPase activities. PMID- 1412539 TI - [The results of the hirudotherapy of patients with paresthesia of the oral mucosa]. AB - Presents the immediate and late (a follow-up of up to 3 years) results of the treatment of 30 patients with oral mucosa paresthesia by the method of hirudotherapy. Discusses the factors influencing the treatment efficacy and leading to recurrences of the disease. PMID- 1412540 TI - [The use of hyperbaric oxygenation and helium-neon laser radiation in the combined treatment of patients with odontogenic phlegmons of the face and neck]. PMID- 1412541 TI - [The role of the genotype in the development of suppurative inflammatory complications in trauma to the facial bones]. AB - The distribution of the genetic markers of leukocytes (HLA I and II), serum proteins (allotypes Gm, transferrin, haptoglobin, group-specific component), red cell enzymes (acid phosphatase--AP, phosphoglucomutase--PGM, esterase D, adenosine deaminase) was found to be universal in patients suffering from various pyoinflammatory diseases. The incidence of HLA A10, Cw4, DR5 antigens, IgG allotype G1m (2) and phenotype G1m (+1+2) and AP (aa) and PGM (2-2) phenotypes was found increased in patients with maxillofacial suppuration and pyoinflammatory complications of maxillofacial injuries as against normal subjects and patients with maxillofacial injuries without such complications. Traumatic osteomyelitis much more often develops in the carriers of the before genetic markers than in those in whom these markers are absent (61.6 and 20.4%, respectively). PMID- 1412542 TI - [The reasons for the overdiagnosis of odontogenic infection due to Staphylococcus and a complex bacteriological approach to detecting an association of causative agents]. PMID- 1412543 TI - [The medical procedure when a tooth is present in the line of a mandibular fracture]. PMID- 1412544 TI - [Disorders of immunity, nonspecific resistance and hemostasis in patients with mandibular fractures who abuse alcohol]. PMID- 1412545 TI - [The clinico-morphological characteristics of the regional blood circulation of the parotid glands in patients with chronic parenchymatous parotitis]. AB - Regional circulation in the parotid glands was studied in 34 patients with chronic parenchymatous parotitis (CPP) with the use of clinical (rheography and coagulography) and morphologic methods. A relationship has been revealed between regional circulation changes and the inflammation severity, CPP stage, type of concomitant diseases. PMID- 1412546 TI - [The potentials of a cytological method for studying the lymph nodes in the neck]. AB - Diagnostic potentialities of the cytologic method for the detection of local metastases on the neck were under study. Three groups of lymph nodes, characterized by different clinical manifestations, were distinguished: nonmetastatic nodes, nodes suspected for metastases, and nodes clinically identified as metastatic. The sensitivity, specificity and accuracy of the cytologic method for all these three groups have made up 87.6, 86, and 93.5%, respectively. Diagnostic errors occurred in only 6.5% of cases. In 20 patients (7.2%) the cytologic findings helped correct the previous erroneous clinical diagnosis. PMID- 1412547 TI - [An evaluation of the body's immune response under the influence of cryosurgery on cancer of the lower lip]. PMID- 1412549 TI - [The development of a subsystem for the automated input and analysis of clinico diagnostic information in oral surgery clinic]. PMID- 1412548 TI - [The characteristics of the removal of fatty masses from the submandibular and the parotid-masticatory areas in benign symmetrical lipomatosis (Madelung's disease)]. PMID- 1412550 TI - [Enzyme immobilization on the dental enamel and its probable role in the physiology and pathology of the oral cavity]. AB - Immobilized alkaline phosphatase was detected on the dental enamel surface of man by histochemical analysis for the first time. A heretofore unknown mechanism of the regulation of metabolic processes on the enamel-saliva border is discussed. Experimental findings confirm that irreversible absorption represent the immobilization mechanism. A new mechanism of enamel remineralization is suggested: that due to phosphatase-active proteins. PMID- 1412551 TI - [The determination of the area and closeness of the fit of the dental arches]. AB - A device and method for estimation of the area and tightness of the dentition contact are described, based on the photoelectric effect. Characteristics of the material used to obtain the occlusion impression are presented. PMID- 1412552 TI - [A comparative evaluation of fixed dentures with metal ceramic and titanium nitride coatings]. AB - The authors emphasize that cermet and metal plastic dentures should be widely used in practical orthodontics. They suggest new approaches to the selection of indications for the tooth preparation to cast dentures in view of the necessity of coating these dentures. The shortcomings of dentures with titanium nitride coating are disclosed. PMID- 1412553 TI - [The compatibility of dentures made from precious metals and from corrosion resistant steels with nitride coatings]. AB - Measurements of electrode potentials of individual half-cells and galvanic currents between dentures made of gold, silver-palladium alloys, and stainless steel with titanium nitride coating, carried out in conditions of mechanic activation, have revealed that these parameters did not surpass the values characteristic of homogeneous elements. Therefore the aforesaid alloys are fairly well compatible in the oral cavity and may be combined in denture making. PMID- 1412554 TI - [The dynamics of the basic autonomic body functions of patients during a consultation with the orthodontist]. AB - Vegetotropic effects of several psychotropic drugs were studied, based on the time course of vegetative symptoms. Computer-based automated diagnostic complex, developed by the author, was used in the study. A total of 261 patients aged 17 to 61, afraid of stomatologic manipulations, were examined. Psychotropic drugs normalized the principal vegetative functions of the body. This fact confirms not only the psychotropic, but the vegetotropic effect of these drugs. PMID- 1412555 TI - [The dynamic indices of dental caries in first-graders in Donetsk Province over the last 25 years]. PMID- 1412556 TI - [A chewing gum with mineral additives]. AB - Finely dispersed hen egg shell was added to a new chewing gum as a mineral component. The studies carried out in 28 schoolchildren have shown that 15 min chewing of this gum results in a marked elevation of salivary Ca levels and in improvement of the hygienic status of the oral cavity. This fact recommends this chewing gum as an additional means for care of the oral cavity for both hygienic purposes and for improving the mineralizing potential of the saliva. PMID- 1412558 TI - [The comparative characteristics of the parameters of the temporomandibular joint and skull in children with bite anomalies]. AB - The authors compare the mean values of 5 parameters of the temporomandibular joint and 19 skull parameters, analyzing 155 tomograms of the joint and 246 teleroentgenograms of the head of children with sagittal and vertical occlusion abnormalities during change of teeth and in permanent occlusion. This comparison has revealed a relationship between the parameters of the temporomandibular joint and the skull. The correlations were the most marked between the height of the mandibular head, height of the mandibular fossa, on the one hand, and anterosuperior and total posterior heights of the face, length of mandibular body and height of its branch, on the other hand. The longitudinal size of the mandibular head corresponded to the longitudinal size of the base of the skull, maxilla, and the angle of the skull base inclination. Complete harmony between the longitudinal and vertical sizes of the skull is observed after change of teeth. PMID- 1412557 TI - [The clinico-experimental validation of the use of low-intensity laser radiation for the treatment of exacerbated recurrent herpetic stomatitis in children]. AB - Experimental data are presented, validating the use of low-intensity laser irradiation at a wave length of 633 nm for the treatment of chronic recurrent herpetic stomatitis. Clinical trials were carried out in 167 children. Laser exposure with the optimal stimulating parameters was found to be an effective means for the treatment of children suffering from this condition. PMID- 1412559 TI - [AN experimental study of the action of industrial aerosols and toxic gases on dental status]. AB - Experiments with white rats have demonstrated that exposure to adverse factors of industrial environment (aerosols and gases) results in increased incidence of caries (by 30-40%) and in a more grave course of the carious process. These changes course along with disorders of the metabolic processes, of the blood and salivary enzymatic systems first of all. PMID- 1412560 TI - [Endoscopy of the antrum of Highmore as a means for choosing the method in treating odontogenic maxillary sinusitis]. PMID- 1412561 TI - [Drug therapy in periodontology: from stereotypes and empiricism to reality]. PMID- 1412562 TI - [A collar-shaped splint in plastic operations on the neck]. PMID- 1412563 TI - [The optimized teaching of an integrated course of radiodiagnosis in a dentistry department]. PMID- 1412564 TI - [The achievements and problems of delivering dental care to the elderly in the USA (a review of the literature)]. PMID- 1412565 TI - [The mechanisms of the adaptation of the neuromuscular apparatus to removable dentures (a review)]. PMID- 1412566 TI - [Clinical and technical measures to improve the fit of whole-cast fixed dentures to the denture bed]. AB - Basing on the literature data and their clinical experience, the authors analyze the following factors influencing the union of whole-cast permanent dentures and denture bed: shape of the prepared tooth, use of various types of benches, presence of free space for cement, compensation for the alloy shrinkage, simplification of placing the dentures by perforating the crowns, use of vibration, lesser volumes of cement put into the crown, and various methods of transferring the masticatory pressure to the denture over the course of denture fixation. Practical significance of these factors is estimated. PMID- 1412567 TI - Studies on anabolic steroids. 9. Tertiary sulfates of anabolic 17 alpha-methyl steroids: synthesis and rearrangement. AB - A simple and convenient method has been developed to prepare sulfates of anabolic 17 beta-hydroxy-17 alpha-methyl steroids. The sulfates of methandienone, 17 alpha methyltestosterone, mestanolone, oxandrolone, and stanozolol were prepared. Different A-ring functions were not affected under the sulfation condition. The buffered hydrolyses of these sulfates provided the 17-epimers of the original steroids and 17,17-dimethyl-18-nor-13(14)-ene steroids, presumably via the 17 carbocations. PMID- 1412569 TI - Stereochemical aspects in the enantioselective synthesis of cortisone by the indan synthon method. PMID- 1412568 TI - Androgen metabolism assessment by routine gas chromatography/mass spectrometry profiling of plasma steroids: Part 1, Unconjugated steroids. AB - Using gas chromatography/mass spectrometry we have developed a method for the simultaneous determination of six plasma steroids: testosterone, 4 androstenedione, 17 alpha-hydroxyprogesterone, 5 alpha-androstane-3 alpha,17 beta diol, 5 alpha-dihydrotestosterone, and dehydroepiandrosterone. For each analyte, a deuterium-labeled internal standard was used for quantification. Due to the high isotopic purity of our standards, no complex corrections for isotope contributions were necessary. The procedure provides a sensitive and specific technique with good accuracy and precision. PMID- 1412570 TI - Hepatic metabolism of 3-oxoandrost-4-ene-17 beta-carboxylic acid in the adult rat: formation of carboxyl-linked glucuronides both in vivo and in vitro. AB - The hepatic metabolism of 3-oxoandrost-4-ene-17 beta-carboxylic acid (etienic acid), a probable acidic catabolite of deoxycorticosterone, was investigated using rats prepared with an external biliary fistula. Metabolic products were identified by GC-MS after hydrolysis with beta-glucuronidase and by proton nuclear magnetic resonance after chromatographic purification of protected glucuronides. About 80% of the injected dose was secreted into bile in 20 hours. Three fully reduced etianic acids (3 alpha-hydroxy-5 alpha-, 3 beta-hydroxy-5 alpha-, 3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acids) were identified as were several of their di- and trihydroxylated congeners. Glucuronides of these reduced and/or hydroxylated metabolites constituted over half of the recovered dose, with carboxyl-linked glucuronides predominating over 3-hydroxyl-linked glucuronides. The mode of glucuronidation correlated well with the ability of liver microsomes to form the corresponding compounds in vitro from the set of four 3,5-diastereomeric etianic acids. PMID- 1412571 TI - Influence of glucocorticoid on the metabolism of aldosterone in the isolated perfused rat liver and kidney. AB - The effect of glucocorticoid deficiency and excess on the extraadrenal metabolism of D-[4-14C]aldosterone (at 4 nM) was studied by radioimmunoassay and by high performance liquid chromatography in the isolated perfused liver and kidney of adult Wistar rats. Bilateral adrenalectomy was performed 3 weeks before experiments. In nonadrenalectomized rats, 0.3 mg/kg/day dexamethasone was continuously infused subcutaneously for 1 week before experiments. Adrenalectomy did not affect hepatic or renal metabolism of aldosterone. Dexamethasone treatment did not change the renal handling of aldosterone. However, the hepatic clearance of aldosterone was 19% lower (P less than 0.05) in livers of dexamethasone treated rats than in livers of normal rats. After 5 minutes, perfusate [4-14C]aldosterone metabolites were lower in livers of dexamethasone treated than in livers of normal rats (P less than 0.05). Similar perfusate levels were then obtained. Radiometabolite peaks with similar relative retention times were found in the hepatic perfusate of all groups. However, the ratio between circulating polar metabolites of aldosterone and the metabolites less polar than tetrahydroaldosterone, after 5 and 15 minutes, was highest in livers of dexamethasone-treated rats. Biliary elimination of 14C was similar in all groups. Significant amounts of conjugated tetrahydroaldosterone were only excreted in the bile of dexamethasone-treated rats. In conclusion, glucocorticoid excess reduced the hepatic clearance of aldosterone and changed the pattern of the hepatic metabolites of aldosterone both in circulation and in bile. PMID- 1412572 TI - Two new 9,11-secosterols from the marine sponge Spongia officinalis. Synthesis of 9,11-seco-3 beta,6 alpha,11-trihydroxy-5 alpha-cholest-7-en-9-one. AB - Two new 9,11-secosterol, 9,11-seco-3 beta,6 alpha,11-trihydroxy-5 alpha-cholest-7 en-9-one (2) and 9,11-seco-3 beta,6 alpha,11-trihydroxy-24- methylene-5 alpha cholest-7-en-9-one (3), have been isolated from the marine sponge Spongia officinalis and their structures elucidated by analysis of spectral data including 1H nuclear magnetic resonance correlation spectroscopy (COSY) experiments. Partial synthesis of 2 starting from 3 beta,6 alpha-dihydroxy-9-oxo 9,11-seco-5 alpha-cholest-7-en-11- al (1) confirmed the structure assignment. PMID- 1412573 TI - Low-dose aspirin and stroke. "It ain't necessarily so". PMID- 1412574 TI - Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin. AB - BACKGROUND AND PURPOSE: The purpose of this study was to compare the effects of low-to-high doses of aspirin on platelet aggregability determined by different methods and on the metabolism of thromboxane A2 and prostacyclin. METHODS: We administered increasing doses (40, 320, and 1,280 mg/day) of aspirin to 19 poststroke patients and studied the differences in 1) the changes in platelet aggregability depending on the methods of evaluation and 2) the concentrations of prostaglandin metabolites in the blood and urine. RESULTS: Aggregation of platelet-rich plasma induced by a strong stimulus (10 microM ADP) was significantly reduced after 40 mg/day aspirin (p less than 0.005), and this reduction was similar to that after higher aspirin doses. In contrast, aggregation of platelet-rich plasma induced by weaker stimuli (1 and 5 microM ADP) decreased less significantly after 40 mg/day aspirin compared with that after higher aspirin doses. The serum thromboxane B2 generated after ex vivo incubation was reduced significantly (by 85%) after 40 mg/day aspirin and decreased further after 320 mg/day (by 96%) and 1,280 mg/day (by greater than 99%) of aspirin. The urinary 11-dehydro-thromboxane B2 concentration decreased less significantly after 40 mg/day aspirin (by 42%) compared with that after 320 mg/day (by 78%) and 1,280 mg/day (by 91%) aspirin doses. The urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha did not decrease after 40 mg/day aspirin but decreased significantly after higher doses of aspirin. CONCLUSIONS: These findings suggest that different doses of aspirin may be necessary to prevent thrombogenesis induced by different triggers of different strengths and that 40 mg/day aspirin is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition. PMID- 1412575 TI - Hematogenous factors and prediction of delayed ischemic deficit after subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Delayed ischemic deficits contribute to the high morbidity and mortality rates associated with subarachnoid hemorrhage. We evaluated the potential usefulness of measuring coagulation and hemorheological variables and cardiolipin antibodies for prediction of delayed ischemic deficit after subarachnoid hemorrhage. METHODS: Consecutive patients with subarachnoid hemorrhage were studied. Coagulation and hemorheological variables and cardiolipin antibodies were measured on admission, within 7 days of subarachnoid hemorrhage. A subset of patients was studied on admission and at two subsequent occasions. RESULTS: Sixty-nine patients were studied. Sixty-one of these were without clinical manifestations of vasospasm at admission, and 16 developed delayed ischemic deficit during their hospitalization. None of the laboratory variables measured were significantly different between patients with or without later development of delayed ischemic deficit. Elevation of the fibrin fragment D dimer was found in the group of eight patients admitted with ischemic symptoms and in 49% (34 of 69) of all patients, but this was not associated with delayed ischemic deficit. Sixteen patients were studied on three occasions; this group showed a significant decrease in hematocrit, an increased white blood cell count, and no change in fibrinogen concentration. Fibrin D-dimer levels rose significantly after surgery (from 5.01 +/- 0.69 to 5.53 +/- 0.58 ln-ng/ml, p less than 0.025) and after onset of delayed ischemic deficit (from 4.71 +/- 0.64 to 5.84 +/- 0.34 ln-ng/ml, p less than 0.01). CONCLUSIONS: Hemostatic measurements, hemorheological variables, and cardiolipin immunoreactivity did not predict delayed ischemic deficit in this population. PMID- 1412576 TI - Stroke incidence rates were unchanged, while fatality rates declined, during 1971 1987 in Goteborg, Sweden. AB - BACKGROUND AND PURPOSE: Stroke risk factors have been shown to change with time in several places; simultaneously, stroke incidence rates have increased in some and decreased in other places. In Goteborg, Sweden, cardiovascular epidemiological research has included stroke registration since 1971. From these data on stroke, incidence and fatality rates from a 17-year period are given. METHODS: During the period 1971-1987 all cases of stroke occurring in people aged 15-65 years in the city of Goteborg were uniformly recorded, with an estimated case detection rate of 90% or more. RESULTS: Age-adjusted incidence rates of first-ever stroke by sex did not change during the period. Age-specific rates and rates for individual types of stroke (subarachnoid hemorrhage, intracerebral hemorrhage, and cerebral infarction-unspecified stroke combined) were also largely unchanged. A slight increase in the incidence rate of intracerebral hemorrhage may be due to better detection after computed tomography came into use in 1976. Stroke fatality rates declined through the whole period in both sexes and all age groups, markedly so for intracerebral hemorrhage and subarachnoid hemorrhage. CONCLUSIONS: This conforms with vital statistics for Goteborg and for Sweden of declining stroke mortality during the period. The decline in stroke fatality rates may be related to decreases in smoking habits and blood pressure together with an increase in the percentage of people on antihypertensive treatment among middle-aged men, and to some extent even middle-aged women, reported from the same population. Why stroke incidence rates did not decline concomitantly is unexplained. PMID- 1412577 TI - Impact of unruptured intracranial aneurysms on public health in the United States. AB - BACKGROUND AND PURPOSE: Unruptured intracranial aneurysms constitute a significant public health problem that has not been quantified. The purpose of this study is to document the magnitude of this problem in the United States. METHODS: National Hospital Discharge Survey data from 1979, 1984, and 1989 served as the basis for calculating patient numbers and frequency distributions. Cost estimates included the direct costs of hospitalization and surgery for those who had surgery, disability and lost income from morbidity, and lost income from mortality. RESULTS: The estimated lifetime cost (including hospitalization, surgery, morbidity, and mortality) for annual cases of patients hospitalized with unruptured intracranial aneurysms in the United States is $522,500,000 compared with $1,755,600,000 for patients with aneurysmal subarachnoid hemorrhage. CONCLUSIONS: These data underscore the need to better understand unruptured intracranial aneurysm as a risk factor for subarachnoid hemorrhage, to define other subarachnoid hemorrhage risk factors, and to optimize the management of patients with these conditions. PMID- 1412578 TI - Circadian rhythmicity of stroke onset. Intracerebral and subarachnoid hemorrhage. AB - BACKGROUND AND PURPOSE: Our purpose was to describe and further understand the determinants of the time of onset of parenchymatous intracerebral hemorrhage and subarachnoid hemorrhage in patients enrolled in the Stroke Data Bank. METHODS: We analyzed the observed times of onset of intracerebral hemorrhage (n = 237 patients) and subarachnoid hemorrhage (n = 243 patients) compared with expected times of onset if the probability of onset was constant across all time intervals. We also analyzed the role of clinical features (if any) in explaining the findings. RESULTS: For intracerebral hemorrhage, 52.5% of patients reported onset times between 0600 hours and 1400 hours, with peak onset between 1000 and 1200 hours (chi 2 = 62.94, df = 11, p less than 0.001). Patients with subarachnoid hemorrhage were more likely to lack a history of hypertension compared with patients who had intracerebral hemorrhage (chi 2 = 23.3, df = 1, p less than 0.001). Patients with subarachnoid hemorrhage were more likely to have more uniform onset time throughout the day (chi 2 = 12.92, df = 7, p = 0.074). However, subarachnoid hemorrhage patients with a history of hypertension were more likely to have peak onset times in mid-to-late morning compared with patients without such a history (chi 2 = 35.25, df = 10, p less than 0.001). The nonuniformity of onset times for intracerebral hemorrhage persisted even if patients with unknown onset times were treated as through their onset times were randomly distributed between 0000 and 0800 hours. Seasonal periodicity and the relation between initial systolic or diastolic blood pressure and time of onset for either type of hemorrhage were not observed. CONCLUSIONS: Our data suggest that the time of onset for both intracerebral hemorrhage and subarachnoid hemorrhage patients with a history of hypertension is similar to the diurnal variation in blood pressure. PMID- 1412579 TI - Assessment of intracranial hemodynamics in sleep apnea syndrome. AB - BACKGROUND AND PURPOSE: Sleep apnea syndrome may lead to changes in cerebral hemodynamics due to altered alveolar ventilation. We investigated the dynamics of CO2- and blood pressure-regulated alterations of cerebral blood flow velocities during apneic episodes and evaluated CO2 reactivity during different sleep stages. METHODS: A computer-assisted pulsed Doppler system (2 MHz) was used for continuous overnight recordings of middle cerebral artery flow patterns together with simultaneous polysomnography, continuous blood pressure recordings, and measurements of end-expiratory CO2 in six patients with sleep apnea syndrome. RESULTS: Increases in mean flow velocity of 19-219% and in blood pressure of 12.5 83.1% could be observed during the apneic episodes, with maximum increases during rapid eye movement (REM) sleep. CO2 reactivity was in the normal range (4.4 +/- 1.2%) in the waking state and was markedly increased during sleep stages 1 and 2 (p less than 0.005 compared with awake). The greatest increase was found during REM sleep, with a rise of up to three times the waking value (p less than 0.0001 compared with sleep stage 2). CONCLUSIONS: The changes of mean flow velocity could be interpreted as reactive adaptation processes because of CO2 and blood pressure increases corresponding to apnea. The increased CO2 reactivity during sleep may indicate a "hypersensitivity" of intracranial vascular CO2 or pH receptors and a disturbance of central catecholaminergic and cholinergic systems. The pronounced velocity changes during apneic episodes and the concomitant alterations of vessel wall tension might lead to microangiopathies and macroangiopathies due to chronic strain on the brain vessels. PMID- 1412580 TI - Leukoaraiosis in relation to prognosis for patients with lacunar infarction. AB - BACKGROUND AND PURPOSE: Close relations between leukoaraiosis detected by computed tomography or magnetic resonance imaging and stroke, particularly lacunar infarction, have been reported. We studied whether leukoaraiosis is related to long-term prognosis for patients with lacunar infarction. METHODS: We examined monthly 215 patients with lacunar infarction after their first stroke. They comprised 95 patients with leukoaraiosis disclosed by computed tomography on admission (58 men and 37 women; mean age, 71.3 +/- 9.0 years) and 120 patients without leukoaraiosis (81 men and 39 women; mean age, 65.5 +/- 8.9 years). These patients had no previous history of either stroke or obvious dementia before their index stroke. We compared the prognosis with and without leukoaraiosis based on analysis of recurrent stroke, survival, and the prevalence of dementia and rate of dependence in activities of daily living. RESULTS: Life table analysis revealed that the recurrent stroke rate was significantly higher in the patients with leukoaraiosis than in those without it (p = 0.004). The prevalence of dementia and rate of dependence in activities of daily living both 1 month after the index stroke and at the end of the follow-up period were significantly higher in the patients with leukoaraiosis (all parameters, P less than 0.001). Their survival rate was significantly lower than in those not suffering from leukoaraiosis (p = 0.012). Significant differences in these comparisons were also observed after matching for age and sex. CONCLUSIONS: The presence of leukoaraiosis as identified by computed tomography indicates a poor prognosis for patients with lacunar infarction. PMID- 1412581 TI - Relation between middle cerebral artery blood flow velocity and stump pressure during carotid endarterectomy. AB - BACKGROUND AND PURPOSE: Many patient monitoring techniques have been used for detecting cerebral hypoperfusion during carotid endarterectomy. We compared middle cerebral artery blood flow velocities with carotid artery stump pressures to evaluate the indications for common carotid artery cross-clamp shunting and the probable hemodynamic causes of cerebrovascular complications. METHODS: Blood flow velocities were monitored with transcranial Doppler ultrasound and carotid stump pressures were measured at the time of common carotid artery cross-clamping during 97 carotid endarterectomy procedures. Stump pressures measured with the gauge zero reference at the common carotid artery level were correlated with the percentage change of velocities. RESULTS: Middle cerebral artery blood flow velocities usually decreased upon common carotid artery cross-clamping, depending on collateral availability and the autoregulation response. The best fit of the data was to an exponential function concave to the pressure axis, with velocity as a percentage of the pre-cross-clamp value reaching zero at 15 mm Hg stump pressure (r = 0.85 and p less than 0.001). CONCLUSIONS: There is a less critical margin of error with percentage middle cerebral artery blood flow velocity decreases than with stump pressure measurements. This relation establishes changes in middle cerebral artery blood flow velocities as a reliable parameter for judging the effects of carotid cross-clamping on cerebral blood flow and providing an excellent indicator as to the necessity for shunting. PMID- 1412582 TI - Anosognosia in patients with cerebrovascular lesions. A study of causative factors. AB - BACKGROUND AND PURPOSE: Psychological and biological hypotheses have been proposed to explain anosognosia. We correlated the presence of anosognosia with the presence and severity of psychiatric disturbances, neglect, intellectual impairments, and computed tomographic evidence of lesion size, location, and measurements of brain atrophy. METHODS: A series of 80 patients with acute stroke were assessed using a battery of psychiatric and neuropsychological tests and computed tomography. RESULTS: There were five main findings. First, 27 (28%) of the 96 patients originally screened showed anosognosia. Second, patients with anosognosia had significantly higher frequencies of hemispatial neglect and related phenomena, as well as deficits in recognizing facial emotions and in receptive prosody. Third, depression was equally frequent among patients with and without anosognosia. Fourth, patients with anosognosia had a significantly higher frequency of right hemisphere lesions, primarily involving the temporoparietal junction, thalamus, and basal ganglia. Fifth, patients with anosognosia showed significantly more subcortical brain atrophy, primarily involving the frontal white matter and diencephalic areas. CONCLUSIONS: The present study demonstrates that anosognosia does not "protect" stroke patients from depressive feelings; rather, it represents arousal-attentional disorders after lesions in specific areas of the right hemisphere in nonaphasic patients with preexisting subcortical atrophy. PMID- 1412583 TI - Beneficial effect of mild hypothermia and detrimental effect of deep hypothermia after cardiac arrest in dogs. AB - BACKGROUND AND PURPOSE: Mild cerebral hypothermia (34 degrees C) induced immediately after cardiac arrest improves outcome. Deep postarrest hypothermia (15 degrees C) has not been studied. METHODS: We used our dog model of normothermic ventricular fibrillation (no blood flow) of 12.5 minutes, reperfusion by brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 72 hours. Head surface cooling and bypass cooling were performed from start of reperfusion to 1 hour. Five groups of six dogs each were compared: group I, normothermic controls; group II, deep hypothermia (15 degrees C); group III, moderate hypothermia (30 degrees C); group IV, mild hypothermia (34 degrees C); and group V, mild hypothermia with head surface cooling begun during no flow. RESULTS: In control group I, five dogs remained comatose (overall performance category [OPC] 4) and one severely disabled (OPC 3). In group II, four dogs achieved OPC 4 and two dogs OPC 3 (NS versus group I). Compared with group I, OPCs were better in group III (p less than 0.05), group IV (p less than 0.05), and group V (p less than 0.05). Neurological deficit scores were also better in groups III, IV, and V than in groups I or II (p less than 0.05). Total brain histological damage scores were better in group III (p = 0.02), group IV (p = 0.06), and group V (p less than 0.05) than in group I. In group II, OPC and neurological deficit scores were the same and histological damage scores numerically worse than in group I and all were worse than in groups III, IV, and V (p less than 0.05). Cardiovascular complications and myocardial morphological damage in groups II and III were worse than in groups I, IV, and V (p less than 0.05). CONCLUSIONS: Mild or moderate cerebral hypothermia induced immediately after cardiac arrest improves cerebral outcome, more likely when initiated during arrest, whereas deep postarrest hypothermia can worsen cerebral and cardiac outcome. PMID- 1412584 TI - Effects of ischemia duration on neurological outcome, CA1 histopathology, and nonmatching to sample learning in monkeys. AB - BACKGROUND AND PURPOSE: Male cynomolgus monkeys (n = 10) were subjected to varying durations of global cerebral ischemia to determine the relation between dose (ischemic duration) and response (outcome). METHODS: Each monkey was anesthetized with halothane, and global cerebral ischemia was produced by a neck tourniquet and trimethaphan-induced hypotension. The animal was subjected to 3 (n = 3), 9 (n = 3), or 12 (n = 4) minutes of ischemia. Neurological examinations were performed daily for 30 days or until the monkey was neurologically normal. Approximately 1 month after ischemia, the animal was evaluated for evidence of neurobehavioral abnormalities with the nonmatching to sample test. When testing was complete, the monkey was killed with an overdose of pentobarbital and the brain perfused with formalin and removed for histopathologic analysis, with particular attention devoted to the hippocampal CA1 region. RESULTS: Monkeys subjected to 3 or 9 minutes of ischemia were neurologically normal (except for a very mild injury in one 9-minute animal) immediately after ischemia and had normal CA1 histology. Monkeys subjected to 12 minutes of ischemia were grossly abnormal neurologically after ischemia, but two of the four animals made a complete recovery (neurological deficit score of 0) by 30 days. Monkeys subjected to 12 minutes of ischemia had mild damage in the CA1 region, with all other brain regions appearing normal. None of the animals had demonstrable decrements in neurobehavioral function as measured by the nonmatching to sample test. CONCLUSIONS: We conclude that neurobehavioral testing after global cerebral ischemia in primates is feasible, but the ischemic time necessary to produce CA1 damage that could potentially be quantified antemortem with the nonmatching to sample test is greater than 12 minutes in cynomolgus monkeys and may produce temporary severe gross neurological abnormalities as well. PMID- 1412585 TI - Tirilazad mesylate does not improve early cerebral metabolic recovery following compression ischemia in dogs. AB - BACKGROUND AND PURPOSE: Tirilazad mesylate (U74006F) has been reported to improve recovery following cerebral ischemia. We conducted a randomized blinded study to determine if the drug would improve immediate metabolic recovery after complete cerebral compression ischemia. METHODS: Mongrel dogs were anesthetized with pentobarbital and fentanyl and treated with either vehicle (citrate buffer, n = 8) or tirilazad (1.5 mg/kg i.v. plus 0.18 mg/kg/hr, n = 8). Normothermic complete cerebral compression ischemia was produced for 12 minutes by lateral ventricular fluid infusion to raise intracranial pressure above systolic arterial pressure. Cerebral high-energy phosphate concentrations and intracellular pH were measured by phosphorus magnetic resonance spectroscopy. Cerebral blood flow was measured with radiolabeled microspheres, and oxygen consumption was calculated from sagittal sinus blood samples. Somatosensory evoked potentials were measured throughout the experiment. RESULTS: During ischemia, both groups demonstrated complete loss of high-energy phosphates and a fall in intracellular pH (vehicle, 5.76 +/- 0.23; tirilazad, 5.79 +/- 0.26; mean +/- SEM). At 180 minutes of reperfusion, there were no differences between groups in recovery of intracellular pH (vehicle, 6.89 +/- 0.07; tirilazad, 6.88 +/- 0.18), phosphocreatine concentration (vehicle, 89 +/- 16%; tirilazad, 94 +/- 24% of baseline value), oxygen consumption (vehicle, 2.6 +/- 0.2 ml/min/100 g; tirilazad, 1.8 +/- 0.5 ml/min/100 g), or somatosensory evoked potential amplitude (vehicle, 11 +/- 6%; tirilazad, 7 +/- 4% of baseline value). Forebrain blood flow fell below baseline levels at 180 minutes of reperfusion in the tirilazad-treated animals but not in the vehicle-treated dogs (vehicle, 28 +/- 4 ml/min/100 g; tirilazad, 18 +/- 5 ml/min/100 g). CONCLUSIONS: We conclude that tirilazad pretreatment does not improve immediate metabolic recovery 3 hours following 12 minutes of normothermic complete ischemia produced by cerebral compression. PMID- 1412586 TI - Mechanism of cerebral blood flow augmentation by hemodilution in rabbits. AB - BACKGROUND AND PURPOSE: Hemodilution is known to increase cerebral blood flow, but it is not known whether the increase in flow is a direct result of a decrease in viscosity or whether it may be due to compensatory vasodilatation in response to the decrease in oxygen carrying capacity that results from hemodilution. This study is designed to investigate this question. METHODS: Changes in regional cerebral blood flow were studied in normal and ischemic brains of 15 and 18 rabbits, respectively. In one group of rabbits graded hemodilution was used to reduce arterial oxygen content progressively in stages; in the second group the arterial oxygen content was reduced in similar stages by progressively larger reductions in the concentration of inspired oxygen (hypoxic hypoxia). In the ischemic animals focal ischemia was produced by embolic occlusion of the right middle cerebral artery. RESULTS: In the normal rabbits, hypoxic hypoxia and hemodilution resulted in similar progressive increases in cerebral blood flow as arterial oxygen content fell. In the ischemic animals, there was a significant fall in cerebral blood flow in the ischemic region in all groups after arterial occlusion. Hemodilution resulted in a progressive increase in cerebral blood flow in both ischemic and nonischemic regions. With hypoxic hypoxia, however, cerebral blood flow in the ischemic region showed no increase or a slight decrease. CONCLUSIONS: Even though hypoxic hypoxia results in a marked increase in cerebral blood flow in normal brain, it does not significantly change cerebral blood flow in ischemic brain. In contrast, hemodilution resulting in a comparable degree of hypoxemia is capable of significantly increasing cerebral blood flow in ischemic brain. Therefore, the mechanism of blood flow augmentation by hemodilution in ischemic brain is probably related to a direct hemorheologic effect rather than to the resulting hypoxemia. PMID- 1412587 TI - Effect of diabetes mellitus on flow-mediated and endothelium-dependent dilatation of the rat basilar artery. AB - BACKGROUND AND PURPOSE: Diabetes mellitus may impair endothelium-dependent responses in cerebral arterioles. The basilar artery dilates in response to increases in blood flow. The goal of this study was to examine effects of diabetes mellitus on "flow-mediated" and endothelium-dependent dilatation of the basilar artery. METHODS: Diabetes was induced in rats with 50 mg/kg streptozotocin. Six months later, vessel diameter and velocity of blood flow through the basilar artery were measured using a cranial window in anesthetized rats under baseline conditions and during occlusion of the carotid arteries. Changes in vessel diameter were also measured during topical application of acetylcholine and sodium nitroprusside. RESULTS: With aortic pressure maintained at baseline levels, blood flow velocity through the basilar artery increased similarly in control and diabetic rats during unilateral common carotid artery occlusion and during bilateral occlusion. In control and diabetic rats, diameter of the basilar artery increased by 10 +/- 2% and 10 +/- 4% during unilateral occlusion and by 27 +/- 5% and 31 +/- 4% during bilateral occlusion, respectively. Thus, diabetes did not impair flow-mediated dilatation of the basilar artery. In contrast, dilatation in response to 10(-5) M topical acetylcholine was less in diabetic rats (13 +/- 2%) than in control rats (45 +/- 8%) (p less than 0.05). Dilator responses to nitroprusside were not impaired by diabetes. CONCLUSIONS: The findings suggest that diabetes produces impairment of endothelium-dependent responses to acetylcholine, but not flow-mediated dilatation, in the basilar artery. PMID- 1412588 TI - Effect of diabetes mellitus on responses of the basilar artery in rats to products released by platelets. AB - BACKGROUND AND PURPOSE: Aggregation and adherence of platelets to vascular endothelium are increased during diabetes mellitus, and thus responses of cerebral arteries to products released by platelets may have important implications for the pathogenesis of stroke during diabetes. The goal of this study was to determine whether responses of the basilar artery to products released by platelets are altered during diabetes. METHODS: A craniotomy was performed over the ventral medulla to expose the basilar artery. Diameter of the basilar artery was measured using intravital microscopy in nondiabetic and diabetic (50-60 mg/kg i.p. streptozotocin) rats in response to adenosine 5' diphosphate, serotonin, and the thromboxane analogue U-46619. RESULTS: Topical application of 10 and 100 microM adenosine 5'-diphosphate produced only minimal changes in diameter of the basilar artery that were similar in nondiabetic and diabetic rats (p greater than 0.05). At 0.01, 0.1, and 1.0 microM serotonin produced dose-related constriction of the basilar artery that was similar in nondiabetic and diabetic rats (p greater than 0.05). At 0.1 and 1.0 microM U 46619 also produced similar dose-related constriction of the basilar artery in nondiabetic and diabetic rats (p greater than 0.05). CONCLUSIONS: These findings suggest that responses of the basilar artery to products released by platelets are not altered by diabetes mellitus. Thus, it does not appear that alterations in reactivity of the basilar artery to products released by platelets contribute to the pathogenesis of stroke during diabetes. PMID- 1412589 TI - Glucose-associated alterations in ischemic brain metabolism of neonatal piglets. AB - BACKGROUND AND PURPOSE: During global brain ischemia or hypoxia-ischemia in adults, hyperglycemia is deleterious to the brain. In contrast, similar adverse effects have not been found in neonatal animals. This investigation examined neonatal piglets to determine if there were specific alterations of ischemic brain metabolism associated with different systemic glucose concentrations and to potentially clarify the effects of hyperglycemia during ischemia in neonates. METHODS: Two groups of animals (n = 12 in each group) were studied during partial ischemia to compare the effects of hyperglycemia (plasma glucose concentration, 258 +/- 97 mg% [mean +/- SD]) with modest hypoglycemia (plasma glucose concentration, 62 +/- 23 mg%). A broad spectrum of cerebral blood flow reduction was achieved by combining inflation of a cervical pressure cuff with varying degrees of hemorrhagic hypotension. High-energy phosphorylated metabolites, intracellular pH, and cerebral blood flow were simultaneously measured using a magnetic resonance spectroscopic technique. Brain metabolic variables (beta-ATP, inorganic phosphorus, phosphocreatine, intracellular pH) were plotted as a function of blood flow reduction during partial ischemia for each group. RESULTS: During ischemia values of cerebral blood flow were comparably distributed between groups and ranged from 15% to 110% of those of control. At a given reduction of cerebral blood flow, hyperglycemic piglets maintained a higher concentration of beta-ATP (p = 0.011) and had a smaller increase in inorganic phosphorus (p less than 0.001). At cerebral blood flow less than 50% of control, the intracellular pH of piglets with modest hypoglycemia during partial ischemia was never reduced to less than 6.46, whereas intracellular pH fell as low as 5.97 for hyperglycemic animals. CONCLUSIONS: ATP preservation may account for the differing effects of glucose during ischemia in neonates compared with adults, provided that the accentuated brain acidosis is not deleterious to neonatal brain tissue. PMID- 1412590 TI - Effect of lidocaine on somatosensory evoked response and cerebral blood flow after canine cerebral air embolism. AB - BACKGROUND AND PURPOSE: Victims of air embolism often recover rapidly on hyperbaric treatment then deteriorate again, even if hyperbaric treatment is continued. In previous animal experiments, lidocaine has been shown to improve recovery of somatosensory evoked response amplitude after air embolism. However, animals in these experiments rarely deteriorated. We have shown that the induction of air embolism and transient hypertension in canines produces deterioration despite hyperbaric treatment, and we decided to test the effect of lidocaine on somatosensory evoked potential recovery and cerebral blood flow in this model. METHODS: Dogs were treated with repeated doses of lidocaine or equivalent volumes of saline during hyperbaric therapy after internal carotid air embolism and transient hypertension. The investigators were unaware of treatment group assignment during the experiments. The amplitude of the median nerve somatosensory evoked potential and cerebral blood flow measured with carbon-14 labeled iodoantipyrine autoradiography were used to assess effect of therapy. RESULTS: Lidocaine-treated dogs recovered 60 +/- 10% (mean +/- 95% confidence limits) of the baseline somatosensory evoked potential amplitude 220 minutes after air embolism; saline-treated dogs recovered 32 +/- 10% (a significant difference at p less than 0.01). Lidocaine-treated dogs also had higher cerebral blood flow values than saline-treated dogs 220 minutes after air embolism. CONCLUSIONS: Lidocaine ameliorated the delayed deterioration of evoked potential associated with air embolism and hypertension in this canine model. The improved cerebral blood flow may be a mechanism of action of lidocaine or an associated effect of improved neuronal survival. PMID- 1412591 TI - Endothelium-derived relaxing factor modulates noradrenergic constriction of cerebral arterioles in rabbits. AB - BACKGROUND AND PURPOSE: Cerebral arterioles are relatively unresponsive to norepinephrine. We tested the hypothesis that release of endothelium-derived relaxing factor is stimulated by norepinephrine and attenuates adrenergic constriction of pial arterioles. METHODS: In seven anesthetized New Zealand White rabbits, diameter of pial arterioles was measured through a cranial window. Responses to topical application of norepinephrine and arginine vasopressin were examined before and during application of NG-nitro-L-arginine, which inhibits synthesis of endothelium-derived relaxing factor. RESULTS: Norepinephrine (10(-6) M) had no effect (0 +/- 3%, mean +/- SE) on arteriolar diameter under basal conditions. Norepinephrine decreased arteriolar diameter by 15 +/- 4% during application of nitro-L-arginine (10(-4) M) (p less than 0.05 versus basal response). L-arginine inhibited the effect of nitro-L-arginine on responses of pial arterioles to norepinephrine. In contrast to norepinephrine, constrictor responses of pial arterioles to vasopressin were not potentiated by nitro-L arginine. CONCLUSIONS: Norepinephrine, but not arginine vasopressin, releases endothelium-derived relaxing factor, which inhibits constrictor responses of cerebral arterioles in rabbits. This mechanism contributes to the finding that cerebral vessels in rabbits are relatively unresponsive to noradrenergic stimuli. PMID- 1412592 TI - Oral administration of glycerol may not cause hemolysis. PMID- 1412593 TI - Cerebrovascular responsiveness to hypercapnia in Alzheimer's dementia and vascular dementia of the Binswanger type. PMID- 1412594 TI - Failure of magnetic resonance imaging in the detection of pontine lacune. PMID- 1412595 TI - Maintenance payments for child support in southern Africa: using law to promote family planning. AB - This article presents some of the legal, social, cultural, and practical constraints facing women who attempt to enforce their right to maintenance (child support) payments in southern Africa. It is based on research by the Women and Law in Southern Africa Trust, a network of women who research women's legal rights in six countries: Botswana, Lesotho, Mozambique, Swaziland, Zambia, and Zimbabwe. Statutes in all countries in the region provide that a man must support his legitimate and illegitimate children; there are, however, weaknesses in the laws on the books. The social and cultural constraints that influence the enforcement of maintenance laws include women's lack of knowledge of the law, attitudes toward child support influenced by customary law, allegations of women's abuse of maintenance payments, financial and practical problems, and fear of physical violence or other forms of retribution. Maintenance laws are relevant to family planning in that if such laws were more effectively enforced, so that the financial burden of children were more equally shared between women and men, men would have a financial stake in controlling their fertility. PMID- 1412596 TI - Contraceptive use in Matlab, Bangladesh: the role of gender preference. AB - Research in several Asian societies has suggested that sons are generally preferred over daughters. The implications of gender preferences for actual fertility behavior have not been adequately investigated, however. This analysis examines the effect of the sex composition of surviving children on the acceptance and discontinuation of contraception in a sample of 3,145 women in Matlab, Bangladesh, who were observed for 60 months. Hazards regression analyses are employed in the analysis. Strong and highly significant effects of gender preference on contraceptive use are observed. The preference is not monotonically son-biased but is moderated toward a balanced composition, because parents desire to have several sons and at least one daughter. These findings suggest that gender preferences, particularly a preference for sons, represent a significant barrier to fertility regulation in rural Bangladesh. PMID- 1412597 TI - Preceding birth intervals and child survival: searching for pathways of influence. AB - The importance of the length of preceding birth intervals for the survival chances of young children has been established, but the debate concerning the causal biomedical or behavioral mechanisms continues. This article uses data from 17 Demographic and Health Surveys to investigate the effect of birth intervals on child mortality: Anthropometry of children, recent morbidity of children, and use of health services are examined in addition to child survival data for children born in the five years before the survey. Various methodological approaches are used to investigate the relative importance of the postulated mechanisms linking birth intervals and child survival. Short preceding birth intervals are associated with increased mortality risks in the neonatal period and at 1-6 months of age, and, to a much lesser extent, at 7-23 months of age. The effects of short birth intervals on nutritional status are rather moderate, and there is a weak relationship with lower attendance at prenatal care services. No consistent relationship exists between the length of birth intervals and other health status or health-service utilization variables. The results indicate that prenatal mechanisms are more important than postnatal factors, such as sibling competition, in explaining the causal nature of the birth interval effect. PMID- 1412598 TI - Fertility and contraceptive adoption and discontinuation in rural Kenya. AB - After a long period of slow progress, the recent uptake of contraceptive use in Kenya has been dramatic. This report describes adoption of a method and method switching and discontinuation among a cohort of married women aged 25-34 in two contrasting rural areas. A retrospective "fertility diary" completed by each woman provided information on spousal separation, reproductive status, and contraceptive use over a period of 46-48 months. Contraceptive prevalence rose rapidly over the period in both areas, with significant net adoption of injectables in both areas and of IUDs in one only. Method discontinuation was concentrated among users of pills, barrier methods, and "natural" methods, and only one-third of all discontinuations were voluntary. The wide differences between the two rural areas in contraceptive prevalence were not totally reflected in recent fertility levels, and the contribution of other proximate determinants of fertility, particularly postpartum amenorrhea and spousal separation, are discussed. PMID- 1412599 TI - Estimates of demand for abortion among Soviet immigrants in Israel. AB - In 1990, more than 185,000 Soviet Jews emigrated to Israel, increasing Israel's population by 4 percent; 148,000 more arrived in 1991. Given the fertility and abortion patterns prevailing among Soviet women in their native country, this article inquires about the short-range expected increase in abortion demand in Israel engendered by this large migratory inflow. Estimation techniques based on the abortion experience of an earlier wave of Soviet-born immigrants in Israel reveal that the increase in requests for abortion brought about by the 1990 immigrants may reach up to 14 percent, and as high as 24 percent for the combined immigration waves of 1990 and 1991. The expanded demand for abortions in Israel engendered by the new Soviet immigrants necessitates an expansion of both family planning services and of the medical committees entitled to grant a legal abortion. A failure in these fields would benefit illegal abortion. PMID- 1412601 TI - Population pharmacokinetics of gentamicin in premature infants. AB - The population kinetics of gentamicin were studied in 97 newborn patients with a gestational age ranging between 28 and 43 weeks and a postnatal age ranging between 2 and 30 days undergoing routine therapeutic monitoring of their serum gentamicin levels. The individual kinetic analysis of serum drug levels was performed using a single-compartment model. The clearance and apparent distribution volume were calculated in each patient. The population model employed assumes the existence of residual variability in the serum concentrations and interindividual variability in the pharmacokinetic parameters. The effects of demographic variables on the clearance, distribution volume, and optimum daily dose of gentamicin were established using multiple linear regression. Gestational age is the best predictive variable of the clearance and the optimum dose/day in the whole population studied. In the premature infant patients, the predictive capacity increases with postconceptional age. Weight is a good predictive variable of all of the parameters, especially of the apparent distribution volume in the overall population of newborns. Analysis of the population kinetic behavior and optimum dose/day in each subgroup recommends that the interval of drug administration should be increased, keeping the same dose/day ratio, due to the tendency of the drug to accumulate its long half-life, especially in premature babies. PMID- 1412600 TI - Pakistan 1990/91: results from the demographic and health survey. PMID- 1412602 TI - Utility of a one-point (3-hour postdose) plasma metabolic ratio as a phenotyping test using metoprolol in two east Asian populations. AB - We examined the utility of the postdose 3-h plasma metabolic ratio (MR) as a phenotyping method for assessing genetically determined debrisoquine-type oxidation polymorphism after an oral dose of 100 mg of metoprolol tartrate administered to 402 unrelated, healthy, and native East Asian (218 Korean and 184 Japanese) subjects. All of them were phenotyped simultaneously with the reported MR employing urine samples collected during an 8-h postdose period. In the two populations, the distribution histograms and probit plots of log10plasma MRs derived from the metoprolol/alpha-hydroxymetoprolol concentration values indicated a large gap between the extensive and poor metabolizers who were phenotyped by the reported criteria of the 8-h urinary MR. There were statistically significant (p less than 0.001) correlations (rs = 0.688 and 0.810, respectively) between the postdose urinary and plasma MRs in the Korean and Japanese populations. Two poor metabolizers (one each included in the two racial groups) identified according to the 8-h urinary MR gave the greatest plasma MRs (i.e., 549.7 among the Koreans and 150.0 among the Japanese). The results suggest that the one-point, postdose 3-h plasma MR is also useful for the phenotyping purpose of oxidation pharmacogenetic polymorphism of metoprolol, a widely prescribed beta-adrenoceptor blocking drug. PMID- 1412603 TI - Subjective side effects of mianserin in relation to plasma concentrations of mianserin and desmethylmianserin. AB - The main purpose of the present study was to examine the possibility that plasma concentrations of mianserin and its metabolite, desmethylmianserin, might be predicted by recording subjective side effects. In 44 depressed patients, subjective side effects during 3 weeks of treatment with 30 mg of mianserin were evaluated by the UKU Side Effect Rating Scale, and their relationships to plasma concentrations of mianserin and desmethylmianserin were analyzed. There was no significant relationship between plasma concentrations of these compounds and the occurrence of mianserin-induced side effects, except for dryness of mouth during week one. Our study, therefore, suggests that it is difficult to predict plasma concentrations of mianserin and desmethylmianserin based on the occurrence of subjective side effects. PMID- 1412604 TI - Interaction between fluvoxamine and imipramine/desipramine in four patients. AB - We describe four patients in whom the addition of fluvoxamine (100 mg/day) to the treatment with imipramine or desipramine (100-150 mg/day) resulted in a dramatic increase in the plasma concentrations of the tricyclic antidepressants associated with adverse effects. These observations indicate that fluvoxamine inhibits both the demethylation of imipramine and, possibly to a lesser extent, the hydroxylation of desipramine. The combination of fluvoxamine with tricyclic antidepressants should be avoided whenever possible. PMID- 1412605 TI - Therapeutic drug monitoring of retinoids. AB - Retinoids are natural or synthetic compounds related to vitamin A. They are successfully used in the treatment of dermatological disorders. However, one of the limiting factors in the use of retinoids is their huge teratogenic potential. The investigation into the pharmacokinetics and metabolism of retinoids has encountered many difficulties due to lack of suitable techniques to deal with these labile compounds. Because of the teratogenic nature of the retinoids, the sensitivity of the assay is of utmost importance. We report a systematic comparison between two high-performance liquid chromatographic methods used to monitor levels of etretinate and its metabolites acitretin and 13-cis-acitretin in plasma. Our analysis suggests that the column-switching method is superior owing to smaller variability in results and its simplicity. We also describe our therapeutic drug monitoring program for counseling women of reproductive age following etretinate or acitretin exposure. Presently, labeling of etretinate in North America suggests that women should refrain from conception for an undetermined length of time. Assessment of serum concentrations over time is beneficial in defining the length of period to postpone conception. PMID- 1412606 TI - Bioavailability of labetalol in patients with end-stage renal disease. AB - The pharmacokinetics and pharmacodynamics of labetalol were assessed after a single oral and intravenous dose in eight patients with end-stage renal disease (ESRD) maintained on chronic hemodialysis, and in eight age-and sex-matched normal volunteers. The mean area under the serum concentration-time curve, volume of distribution, clearance, and terminal elimination half-life values after a single intravenous dose of 0.5 mg/kg of labetalol were not significantly different between ESRD patients and normal volunteers. Similarly, the absolute bioavailability of an oral dose of 200 mg of labetalol was 0.33 in ESRD patients and was not significantly different from that of normal volunteers (0.26). However, a significant decrease in the area under the mean blood pressure-time curve was found after a single oral dose in ESRD patients, which was not observed in normal volunteers. The pharmacokinetics of labetalol were not associated with changes in blood pressure. Thus, when given orally to the ESRD patient, labetalol should be slowly titrated and the blood pressure closely monitored. PMID- 1412607 TI - Radioimmunoassay for ceronapril, a new angiotensin-converting enzyme inhibitor, and its application to a pharmacokinetic study in healthy male volunteers. AB - Ceronapril is a member of a new chemical class of angiotensin-converting enzyme inhibitors being developed by The Bristol-Myers Squibb Pharmaceutical Research Institute. A radioimmunoassay (RIA) has been developed for the measurement of ceronapril in biological fluids. The RIA has a range of 0 to 500 ng/ml and has the sensitivity to detect 1.0 ng/ml of ceronapril. Satisfactory zero binding and sensitivity were obtained after a 2-h incubation at room temperature or overnight at 4 degrees C. Separation of the antibody-bound and free radiolabel was achieved by employing polyethylene glycol-goat anti-rabbit gamma-globulin separant. A quantitative recovery of the exogenous analyte was obtained at all concentrations of ceronapril tested. Intraassay coefficients of variance (CV's) were 3.9% and 4.6% for the low and medium controls, respectively. A highly significant statistical correlation between RIA and [14C]TLRC was observed for both plasma and urine samples. Clinical samples from the ascending dosage studies have been analyzed by the ceronapril RIA. The maximum concentration and the area under the plasma concentration-time curve did not increase in a dose-proportional manner for doses above 100 mg. PMID- 1412608 TI - Tissue concentrations of cefepime in acute cholecystitis patients. AB - Cefepime is a new broad-spectrum cephalosporin with activity against Staphylococcus, Streptococcus, Pseudomonas, and the Enterobacteriaceae. The purpose of this study was to measure cefepime concentrations in plasma, peritoneal fluid, bile fluid and appendix tissue in patients undergoing elective cholecystectomy. Patients were randomly assigned to receive either cefepime, 2 g intravenously in phosphate buffer (IVPB) q 12 h or gentamicin 1.5 mg/kg IVPB q 8 h plus mezlocillin 4 g IVPB q 6 h. During surgery, gall bladder tissue, plasma, peritoneal fluid, and bile fluid samples were obtained at approximately the same time. Thirty-three patients had data acceptable for analysis. Values are given as mean +/- standard deviation. The mean delta time (defined as the time between the administration of cefepime and the time the samples were obtained) was 8.58 +/- 3.53 h. The values for plasma, peritoneal fluid, bile fluid, and gall bladder tissue concentrations were 7.63 +/- 14.17 micrograms/ml, 5.66 +/- 6.80 micrograms/ml, 15.51 +/- 16.94 micrograms/ml, and 5.36 +/- 6.57 micrograms/gm, respectively. The peritoneal fluid/plasma ratio was 2.10 +/- 2.33, the bile fluid/plasma ratio was 14.44 +/- 31.99, and the gall bladder tissue/plasma ratio was 1.44 +/- 1.82. There was a significant correlation between peritoneal fluid and plasma concentration (r = 0.91, p less than 0.0005), and gall bladder tissue and plasma concentration (r = 0.90, p less than 0.0005). There was no correlation between bile fluid and plasma cefepime concentrations. The minimum inhibitory concentration (MIC) data from previous in vitro studies indicate that cefepime concentrations achieved in this patient population would be adequate against typical biliary tract pathogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412609 TI - Specific enzyme-multiplied immunoassay and fluorescence polarization immunoassay for cyclosporin compared with Cyclotrac [125I]radioimmunoassay. AB - The analysis of cyclosporin-A (CsA) has proved a valuable adjunct to clinical care of patients who have received organ grafts. The measurement of CsA in whole blood by specific methods has recently taken a new direction with the introduction of a range of rapid methods, including a homogeneous enzyme immunoassay technique (EMIT) and a monoclonal fluorescence polarization immunoassay (FPIA). The present paper compares these two methods with the established Cyclotrac specific [125I]RIA (radioimmunoassay) using both commercial CsA-spiked control material as well as a group of 60 patient specimens (predominantly renal transplants). While each of the new methods showed acceptable precision and accuracy with the commercial quality control material, significant differences were demonstrated with patient specimens, such that FPIA was 12.5% greater than [125I]RIA (p less than 0.0001), which was in turn 5.9% greater than EMIT (p = 0.007). These data suggested that the FPIA may have residual CsA-metabolite interference and that the EMIT method was the most "specific" for parent CsA of the three tested, potentially therefore more comparable to high-performance liquid chromatography (HPLC). PMID- 1412610 TI - Plasma assay of salbutamol by means of high-performance liquid chromatography with amperometric determination using a loop column for injection of plasma extracts. Application to the evaluation of subcutaneous administration of salbutamol. AB - An isocratic high-performance liquid chromatography method with amperometric detection for the assay of plasma salbutamol is described. The plasma extract is injected into the chromatographic system via a loop column. This insures the purification of the injected extracts and allows a simple and rapid liquid-solid extraction procedure. The good reliability, as shown by the low limit of detection (0.5 ng/ml) and a precision ranging between 5 and 10%, has permitted the investigation of a new mode of administration of salbutamol using a portable subcutaneous infusion pump. Our results show that subcutaneous administration yields plasma levels comparable with those obtained after usual intravenous doses. PMID- 1412611 TI - Determination of salivary digoxin with a dry strip immunometric assay. AB - Analysis of salivary digoxin using a rapid dry chemistry, enzyme-labeled immunometric assay (ELIA) was compared with fluorescence polarization immunoassay (FPIA). Saliva and serum samples were obtained from 40 hospitalized patients who were taking digoxin chronically and from 8 patients just prior to treatment with digoxin. Unstimulated saliva samples were collected from 20 patients; however, saliva volumes from 10 pediatric patients were inadequate to permit analysis by FPIA, and 1 other had unmeasurable concentrations by both methods. Stimulated saliva was collected by having patients chew a small piece of Parafilm for 1-2 min. Salivary digoxin was analyzed using the same procedure recommended for serum digoxin by each manufacturer. There were no significant differences found between ELIA and FPIA determinations of unstimulated or stimulated salivary digoxin, serum digoxin, or saliva/serum concentration ratios. The saliva/serum ratio of the unstimulated group was approximately twice that of the stimulated group (p less than 0.01) by both methods, suggesting that salivary digoxin concentration decreases with increased saliva production rate. Excellent correlations were found between ELIA and FPIA salivary digoxin concentrations and between stimulated saliva and serum concentrations by both assays. Weaker correlations were observed between unstimulated saliva and serum concentrations. There was no evidence of assay interference with either method in eight nondigitalized patients, each taking an average of 6.5 medications. The ELIA appears to provide equivalent results compared with the FPIA for the determination of salivary digoxin concentration. Further investigations are needed before salivary digoxin concentration monitoring can be recommended as an acceptable alternative to serum monitoring. PMID- 1412612 TI - Determination of plicamycin in plasma by radioimmunoassay. AB - This article describes a method for the determination of plicamycin in plasma by radioimmunoassay. The anti-plicamycin antibody was produced against a plicamycin bovine serum albumin conjugate prepared by using diazotized p-aminobenzoic acid as a cross-linker. The radiolabeled ligand, 125I-plicamycin, was prepared by the chloramine-T method. The linear plicamycin concentration range was 7-400 ng/ml. The coefficients of variation for intra- and interday variabilities were 7.5 and 15%, respectively. No interference was observed from either the structurally related chromomycin A or concomitantly used drugs hydroxyurea or allopurinol. With this method of testing, plicamycin levels in plasma could be determined in patients receiving small (0.85-1.0 mg/m2) therapeutic plicamycin doses. Preliminary pharmacokinetic data in humans indicate that the plasma drug disappearance curve was biphasic with a mean elimination half-life of 10.6 +/- 1.7 h, total clearance rate of 11.1 +/- 0.4 ml/min/m2, and area under the plasma drug concentration-time curve of 1,289-1,546 ng-h/ml. This assay method is clinically useful for pharmacokinetic studies of plicamycin and may be helpful in the design of rational therapeutic drug trials. PMID- 1412613 TI - Haloperidol disposition is dependent on the debrisoquine hydroxylation phenotype: increased plasma levels of the reduced metabolite in poor metabolizers. AB - We have previously shown that the disposition of haloperidol is decreased in poor (PM) compared to extensive (EM) metabolizers of debrisoquine. We now report that the plasma levels of the reduced metabolite of haloperidol, after a single 2- or 4-mg oral dose of the parent drug, are significantly higher in PM than in EM of debrisoquine. As PM have higher concentrations of haloperidol than EM, more of the reduced metabolite should be formed, since the formation of reduced haloperidol from haloperidol seems to be independent of the debrisoquine hydroxylase (cytochrome P4502D6) activity. Another reason to explain the increased metabolite levels in PM may be a decreased reoxidation of the reduced metabolite to haloperidol, as this reaction is catalyzed by cytochrome P4502D6. A third reason might be that reduced haloperidol is transformed to other metabolites by this enzyme. PMID- 1412614 TI - [Age discrimination in the labor establishment]. PMID- 1412615 TI - [Nutritional status of elderly patients at admission to a general psychiatric hospital. An inventory]. AB - The nutritional status of 121 psychiatric patients over the age of 60 years was examined on admission in a general psychiatric hospital. Before admission all patients were living independently. They were admitted directly from their homes. We found that the older psychiatric patient is evidently at risk for malnutrition. A quarter of the males had, according to the Quetelet's index, a low weight. Half of the males and one third of the females had a thiamin deficiency, whereas half of all patients showed a deficiency of folic acid. Furthermore, in half of the males and one tenth of the females anaemia was diagnosed. Widowers and to a lesser extent also patients with an organic brain disease or psychotic disturbance ran a greater risk of malnutrition in comparison to their fellow patients. A relation between behaviour, measured by the Nosie (Nursing Observation Scale for Inpatient Evaluation) and the nutritional status was not found. PMID- 1412616 TI - [Assessment of health status of the elderly. Application of a Dutch version of the MOS scale]. AB - The 'MOS Shortform General Health Survey', a measure for assessing general health, has been used in an elderly population in the Netherlands (N = 354). The 20-item (mail) questionnaire comprises six dimensions or subscales: physical functioning (6 items), role functioning (2), social functioning (1), mental health (5), health perceptions (5) and body pain (1). Our results show reasonable psychometric properties of the subscales (internal reliability, skewness and kurtosis of distribution, correlation between subscales and correlation with other health measures, 8 weeks test-retest reliability), which are comparable to those in the United States in a general patient population. The six subdimensions of the scale together seem to meet the criteria of the stochastic cumulative measurement model (Mokken-type scale). The results show that this instrument gives an opportunity to assess general health in the elderly within just a couple of minutes. PMID- 1412617 TI - [Consequences of handicaps following a cerebrovascular accident for patient's partner]. AB - What is the influence of stroke on experienced burden, coping and well-being of the patient's spouse? To explore this problem we interviewed 22 spouses, living with their husband or wife at home. Stroke had occurred over 12 months ago. There appeared to be different consequences for the spouse, depending upon the kind of handicap: The physical handicaps in stroke-patients were associated with an increase of household tasks and caregiving, and with diminished opportunities for the spouse to relax. Mental deterioration after stroke was slightly associated with a lower level of well-being in the spouse. Spouses of patients with severely impaired communication had fewer opportunities to relax, reported more deterioration of the marital relationship and showed slightly more depression than spouses of patients with slightly impaired communication. PMID- 1412618 TI - [Paced addition. A neuropsychological test for assessment of divided attention]. AB - The Pasat (Paced auditory serial addition task) is a test requiring addition of simple digits presented auditorily in several series of a successively higher pace of presentation. The task reflects the capacity for divided attention, is a measure of information processing speed and has appeared to be sensitive to minor attention deficits. We made a Dutch version characterized by longer time intervals between digits, for use in a study among (altogether 130) middle-aged and elderly persons. This modified version was evaluated with respect to feasibility. It appeared to be fairly feasible, provided sufficient opportunity for practice is given. Two series with inter-stimulus intervals of 4 and 3 seconds respectively were then evaluated with respect to validity and reliability in subjects of 48 to 74 years. Both Pasat series correlated well with two tests of attention: Digit Symbol (WAIS) and d2-test (r = 0.53-0.67), the relation with reaction decision speed being generally weak (r = 0.29-0.33) and weak to absent with a number of memory tests (r = -0.04-0.29). The Pasat performance shows a positive relationship with educational level and intelligence (inter-stimulus interval 4 seconds: r = 0.28 and 0.33 resp.; inter-stimulus interval 3 seconds: r = 0.40, 0.57 resp.). The stability of test performance over a period of about two months is moderate (r = 0.54, 0.61 resp.). In view of the excellent inter observer reliability (r = 0.99) and the good parallel-test reliability (r = 0.79, 0.68 resp.), this might be explained by fluctuations in the capacity measured, rather than measurement error.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412619 TI - Recognition and treatment of surgical wound infections. AB - 1. Tissue traumatized by surgery heals in a three-phase sequential process: a defensive response to the injury, reconstruction of the site, and maturation (closing) of the wound. 2. Not all patients undergoing surgery are at equal risk for infection. The anatomic location of the surgery, the seeding of the surgical site with the patient's own normal flora, the OR environment and personnel, and the presence of a foreign body left in place after closure all contribute to the risk of infection. 3. The treatment of postoperative infection can be divided into the physical aspects of wound care and the appropriate use of antimicrobial agents. PMID- 1412620 TI - The facts about methicillin-resistant Staphylococcus aureus. AB - 1. Staphylococcus aureus is a gram-positive organism that can be cultured from the anterior nares of 30% to 40% of the general population. S aureus causes about 10% of all nosocomial infections, and is the leading cause of surgical wound infections. 2. Several factors can influence the recovery of MRSA from specimens, including mixed cultures in the person, a person who is an intermittent carrier, and a culture that is taken or transported incorrectly. 3. Two approaches can be used to reduce the risk of cross-transmission of organisms among patients and health-care workers: a generic infection precautions strategy for all patients, and identifying patients infected or colonized with MRSA and treating them differently than other patients. PMID- 1412621 TI - Reducing occupational exposure to blood in the OR. AB - 1. Many occupational exposures to blood in the operating room can be prevented. Some percutaneous injuries may not be preventable, but their frequency can be reduced by implementing engineering and work practice controls. Work practice controls and personal protective equipment can help eliminate mucocutaneous exposures to blood. 2. Identifying risk factors for intraoperative exposure is a vital step in presurgical and intraoperative assessment to plan infection prevention and control interventions. The decision to use risk reduction strategies should be based on probability and type of exposure anticipated rather than on the index of suspicion for bloodborne infection in the patient. 3. The responsibility for using safety and barrier precautions in the operating room remains that of the health-care worker. Not only the patient, but also the health care worker need to be protected. PMID- 1412622 TI - Important issues in infection: surveillance, prevention, and control. PMID- 1412623 TI - Federal medical waste management: an idea whose time has come. PMID- 1412624 TI - Tuberculosis: the return of a monster. PMID- 1412625 TI - Feeling personal power. AB - Feelings of personal power are important for personal feelings of well-being. Although feelings of personal power relate to authority, either given by others or acquired with the job, personal power is largely a personal feeling that is created and can be developed. Careful assessment of position power, expertise power, and personal characteristics that add or detract from personal power can increase self-awareness and cause strong areas to be maximized and weak areas to be developed. With the development of feelings of personal power come feelings of confidence in a nursing role. Feelings of personal power also benefit the nursing profession because this enables the profession to grow in strength and pride. PMID- 1412626 TI - Surgical wound infection rates: use caution when comparing. AB - 1. Comparing surgical wound infection (SWI) rates without a complete understanding of and at least a partial control for those factors that can account for observed variations can be misleading. 2. Variations in SWI rates can be attributed to patient-related factors, type of operation, differences in case finding, differences in definition of SWI, and chance variation. 3. Use of a risk stratification prior to rate calculation controls for intrinsic (patient-related) and extrinsic (operation-related) risk for the purpose of comparison. PMID- 1412627 TI - Perioperative antibiotic prophylaxis: the importance of timing. AB - 1. Although prophylactic antibiotics have demonstrated efficacy in surgical procedures, they can fail because, generally, an inappropriate agent is used or the agent is inappropriately administered. 2. The timing of administration is important. Studies indicate that to reduce the risk of infection, high levels of antibiotic must be present in the bloodstream and tissues at the time of the incision. 3. Nurses play a central role in ensuring the proper timing of the administration of prophylactic antibiotics. Improvement in the timing of administration will reduce both morbidity and institutional costs. PMID- 1412628 TI - The port: delivering intraperitoneal chemotherapy in ovarian cancer. AB - 1. Ovarian cancer is rarely diagnosed in the early stages because there are no easily identifiable signs and symptoms. When recognizable signs and symptoms appear, they are commonly unimpressive, elusive, and vague. 2. A significant advantage of intraperitoneal administration of chemotherapy is that high concentrations of drugs can be maintained within the peritoneal cavity with less systemic toxicity than with intravenous administration of similar doses. 3. Surgically implanted ports allow for a completely closed system, eliminating the need for daily care and greatly reducing the potential for infection. PMID- 1412629 TI - Intraoperative radiation therapy. AB - 1. Local and regional recurrence of disease is a major problem in cancer management. Intraoperative radiation therapy (IORT) combines surgery with irradiation to treat any disease remaining after surgery and to decrease the local recurrence rates for certain cancers. 2. The development of an IORT treatment program is often undertaken by groups and institutions with expertise in multidisciplinary oncology, particularly surgical and radiation oncology. The program uses multiple resources, requiring cooperation and teamwork to achieve an efficient procedure with maximum patient outcome. 3. The process should be reviewed and modified each time it is performed. There is no "standard" way to use IORT, and every program will have variations that adapt to the circumstances existing in each specific facility. PMID- 1412630 TI - Head and neck cancer resection and reconstruction: from past to present. AB - 1. Head and neck tumors occur predominantly in men between 50 and 70 years of age who typically abuse tobacco or alcohol. These individuals often have poor oral hygiene and dentition as well as nutritional deficits, and achlorhydria, anemia, and iron and riboflavin deficits are common. 2. The tumor and treatment of head and neck cancer may cause many devastating effects, such as facial disfigurement, dysphagia, alterations in airway and communication, partial or total loss of taste and smell, xerostomia, pain, or fatigue. Treatment and rehabilitation may take months. 3. Although advances in technology and reconstructive surgery have not improved the overall survival rate, they preserve appearance, function, and, ultimately, the patient's quality of life. PMID- 1412631 TI - The changing face of cancer. PMID- 1412633 TI - OR fires: do you know what to do? PMID- 1412632 TI - American Cancer Society services for cancer patients. AB - 1. As the incidence of cancer continues to rise among Americans, the number of new cancer patients increases along with the survival rates. It is becoming increasingly important for nurses to recognize and respond to the needs of those living with cancer. 2. Those faced with cancer fear death, disfigurement, financial ruin, and isolation from their friends and loved ones. Patients and families have tremendous needs for assistance but do not know where to turn. Nurses in any practice setting can help these patients access community resources. 3. The American Cancer Society is a national organization offering programs for patients and families in the areas of resources, information, and guidance; education and support programs; and direct services. PMID- 1412634 TI - Breast cancer surgery: understanding the story. AB - 1. Research has shown that mastectomy, with or without reconstruction, is no more effective in the long run than breast conservation and irradiation. Therefore, the important factor seems to be choice. 2. A Halsted radical mastectomy involves the removal of the whole breast along with the pectoralis major and minor muscles and a complete axillary dissection. A modified radical mastectomy involves removal of the whole breast and most or all of the axillary lymph nodes, but preserves the pectoralis major muscle. 3. Breast preserving strategies remove the malignant cells and minimal surrounding tissue. These segmental resections include lumpectomy, quadranectomy, and wedge resection along with axillary node dissection. PMID- 1412635 TI - Malaria resistance genes: a natural selection. PMID- 1412636 TI - A DNA hybridization assay for use in drug sensitivity tests in vitro for Plasmodium falciparum under field conditions. AB - A deoxyribonucleic acid (DNA) hybridization technique was applied to in vitro drug sensitivity testing of P. falciparum using a synthetic 21-mer oligonucleotide coupled to alkaline phosphatase (PFR1-AP) to monitor development of parasite stages in culture. The density of the coloured spot clearly distinguished schizonts from ring forms. This assay system was applied in the field on Hainan Island, China. Blood samples obtained from patients were cultivated in the presence of antimalarial drugs and the minimum drug concentration required to inhibit development of parasites was determined by the DNA hybridization assay and by microscopical observation of Giemsa-stained blood smears. The 2 methods yielded identical results, indicating that the DNA hybridization assay can be used for in vitro drug sensitivity testing under field conditions. PMID- 1412637 TI - Chloroquine sensitivity of Plasmodium falciparum in vivo in a savanna town in Cameroon. AB - Chloroquine-resistant Plasmodium falciparum has been reported in the Sahel and forest regions of Cameroon since 1985. In vivo response to chloroquine treatment (25 mg/kg) was assessed in 19 patients with malaria in the savanna North-West province. 58% of the cases showed RII resistance to chloroquine. RIII resistance was suspected in one patient. Only 35% of cases showed complete parasite clearance by day 5 of treatment. Chloroquine reduced parasite counts by at least 87% in all patients. Chloroquine resistance now seems to be well established and widespread in Cameroon. Its rapid spread and the prevalence of resistance suggest the existence of sustained drug pressure resulting in rapid selection of less sensitive strains. Unfortunately, similar pressure is also being exerted with quinine. PMID- 1412638 TI - Plasmodium falciparum: sensitivity to chloroquine in vivo in three ecological zones in Ghana. AB - 4690 children aged 6-15 years in 5 urban and 4 rural communities in 3 ecological zones in Ghana were screened from June 1988 to December 1990 to provide suitable candidates for the World Health Organization standard in vivo test for susceptibility of Plasmodium falciparum to chloroquine. 1880 (40.1%) had parasitaemia, mostly (83.7-98.6%) due to P. falciparum infection. Of the 626 in vivo tests performed, 570 (91.1%) showed sensitivity to chloroquine and 56 (8.9%) responses were classified as resistant to chloroquine at RI (5.1%) and RII (3.8%). The resistance responses were commonest (17.1-22.7%) in the coastal zone, followed by the savanna zone (8.6-10.0%), and lowest in the forest zone (3.1 6.3%). The RII responses occurred mainly in communities in the coastal zone. There was no RIII resistance in any zone. The pattern of RI (early) and RII responses of P. falciparum to chloroquine in this study suggested an increase in sensitivity, or a reduction in resistance, of P. falciparum to chloroquine from the coast to the forest and northern savanna zones, and from the urban to the rural communities in each zone in Ghana. PMID- 1412639 TI - Halofantrine given with food for falciparum malaria. PMID- 1412640 TI - The activity in vitro of cycloguanil and pyrimethamine in combination against Plasmodium falciparum. PMID- 1412641 TI - Lack of effect of desipramine on the response to chloroquine of patients with chloroquine-resistant falciparum malaria. AB - The potential of desipramine to improve the efficacy of chloroquine against chloroquine-resistant Plasmodium falciparum in vivo in man was investigated. Fifty-three malaria patients were selected according to the criteria for the standard World Health Organization (WHO) in vivo test and were randomly divided in 2 groups. One group (n = 27) was given standard therapeutic doses of chloroquine (25 mg/kg body weight of base) and the other (n = 26) was given standard doses of chloroquine, as above, in combination with desipramine (1.3-2.8 mg/kg body weight) daily for 3 consecutive days. Standard WHO in vitro micro tests were performed in parallel with the tests in vivo to provide chloroquine sensitivity patterns of the P. falciparum parasites. The results in vitro from both groups did not differ with regard to chloroquine sensitivity and the means of the pre-treatment parasite densities were similar. There was no apparent difference in parasite clearance in vivo between the 2 groups. This study provided no evidence for enhanced chloroquine efficacy in vivo through the use of desipramine in doses corresponding to the usual therapeutic range. PMID- 1412642 TI - The role of shops in the treatment and prevention of childhood malaria on the coast of Kenya. AB - A community survey of 388 mothers in a rural and peri-urban population surrounding a district hospital on the coast of Kenya revealed that the preferred choice of treatment for childhood febrile illnesses was with proprietary drugs bought over the counter at shops and kiosks (72% of interviews). 67% of the mothers who reported using shops claimed they would buy chloroquine-based drugs. Preventative measures such as mosquito nets were uncommon (6.2%), but the use of commercial pyrethrum mosquito coils was reported more frequently (46.4%). Separate investigations of treatment given to 394 children before presentation at hospital with severe and mild malaria was consistent with the reports in the community of high usage of shop-bought anti-malarials and anti-pyretics. The involvement of the private sector in peripheral health care delivery for malaria is discussed. PMID- 1412643 TI - Haemoglobin-E in the presence of oxidative substances from fava bean may be protective against Plasmodium falciparum malaria. AB - A case-control study was carried out at a community hospital in eastern Thailand in order to study the association between haemoglobin E and Plasmodium falciparum malaria; 271 P. falciparum cases and 271 controls were enrolled. After adjusting for age, sex, time since last malaria attack, history of mosquito net use, and history of fava bean consumption in the previous month, neither heterozygous nor homozygous haemoglobin E provided significant protection against P. falciparum infection, with odds ratios (OR) = 0.91 (95% confidence limits = 0.61, 1.36) and 0.78 (0.34, 1.82) respectively when compared to persons with haemoglobin A who were not consumers of fava beans. However, haemoglobin E carriers who ate fava beans were significantly protected against P. falciparum malaria with OR = 0.26 (0.09, 0.76) and OR = 0.001 (0.00, 1120.59) for subjects with heterozygous and homozygous haemoglobin E, respectively. The study suggests a possible synergistic protective effect of haemoglobin E on the risk of P. falciparum malaria in subjects who have consumed fava beans. PMID- 1412644 TI - Leishmanin reaction in the human population of a highly endemic focus of canine leishmaniasis in Alpes-Maritimes, France. AB - The reactivity of the human population was studied in the village of l'Abadie, a suburban focus of canine leishmaniasis (17% of dogs seropositive in 1985); 237 subjects were tested in 1989. The total positive rate was 30%. A higher proportion of positive skin tests was obtained in the 61-70 years age group (62%) than in the younger groups. The proportion of positive tests also increased with the duration of living in this locality (22% for less than 5 years; 66% for more than 21 years). These data confirm the continuing occurrence of transmission of leishmaniasis to human beings in this focus. PMID- 1412645 TI - Is leishmaniasis ever cured? AB - The persistence of parasites in mice cured of Leishmania mexicana infection was investigated by using immunosuppressive drugs and checking for the reappearance of lesions. BALB/c (susceptible) and C57BL/6 (partially resistant) mice infected with 10(4) amastigotes were treated with either thermotherapy or meglumine antimonate and subsequently immunosuppressed with either cyclophosphamide or hydrocortisone. Immunosuppression by either method caused lesions to reappear in both strains of mice regardless of the treatment used to produce clinical cure. In both strains of mice the proportion of animals developing lesions after immunosuppression was greater in the mice cured by the drug. The relevance of these findings to human therapy is discussed. PMID- 1412646 TI - High-dose nifurtimox for arseno-resistant Trypanosoma brucei gambiense sleeping sickness: an open trial in central Zaire. AB - Thirty patients with arseno-resistant Trypanosoma brucei gambiense sleeping sickness were treated with high-dose nifurtimox (30 mg/kg/d for 30 d). During treatment, the cerebrospinal fluid (CSF) white blood cell (WBC) count decreased in all patients except one (mean CSF WBC count before nifurtimox: 117/mm3; after nifurtimox: 25/mm3), and trypanosomes disappeared from the CSF of all 9 patients in whom parasites had been demonstrated before nifurtimox. Among 25 patients seen at least once after treatment, 9 (36%) have relapsed so far. High-dose nifurtimox was significantly toxic: one patient died during treatment and 8 others developed adverse neurological effects. High-dose nifurtimox seems more effective than the previously used regimen (15 mg/kg/d for 60 d), but at the expense of significant toxicity. PMID- 1412647 TI - Relative efficacy of melarsen oxide compared with mel Cy (Cymelarsan) when used in combination with difluoromethylornithine in the treatment of trypanosomiasis of the central nervous system. AB - A comparison was made between the efficacy of mel Cy (Cymelarsan) and melarsen oxide to cure central nervous system trypanosomiasis in a chronic Trypanosoma brucei mouse model. Combination treatment with difluoromethylornithine and arsenical was used and it was found that there was only a marginal advantage in using the water-soluble mel Cy in terms of the numbers of mice cured. PMID- 1412648 TI - Detection of high titres of Toxoplasma gondii antibodies in sera of patients with leprosy in Pakistan. AB - Untreated and treated leprosy patients and their household contacts were screened for antibody to Toxoplasma gondii using antigen-coated latex particles. A significantly high level of seroprevalence (29.6%) was observed in the untreated leprosy patients compared to endemic controls (P < 0.01) with a mean reciprocal antibody titre of 20,007 +/- 3580 (n = 98) in seropositive patients. In treated patients seroprevalence dropped to 13.5%. Seroprevalence in a group of household contacts of leprosy patients was similar to that of control subjects from an endemic area but not exposed to leprosy (7.8% and 6.1% respectively), indicating that the increased seroprevalence in leprosy patients was not merely due to increased exposure related to socioeconomic factors. Antigenic cross-reactivity between T. gondii and Mycobacterium leprae antigens was ruled out by cross inhibition experiments carried out with soluble antigens from each of the organisms. We believe these antibodies may be induced by an increase in T. gondii load in leprosy due to a transient reactivation of latent T. gondii infections, as the antibodies in these leprosy patients were not associated with any sign of eye or lymphatic pathology related to toxoplasmosis. PMID- 1412649 TI - Low seroprevalence of Toxoplasma gondii antibodies in a Tanzanian village. AB - The prevalence of antibodies against Toxoplasma gondii was studied in the population of Nyamisati village in Tanzania using the direct agglutination test, indirect immunofluorescence test, and immunosorbent agglutination test. All positive sera were positive by both direct agglutination and indirect immunofluorescence tests and were confirmed by the dye test. The seropositivity was confirmed by immunoblotting showing a distinct 32 kDa band in all the seropositive samples. The seropositivity rate was 4% (19/450) among the subjects of Nyamisati origin and 47% (15/32) among immigrants from other areas of Tanzania. Most of the infections appeared to have occurred between 5 and 15 years of age. The generally low transmission in this mainly Muslim village appeared to be related to sparse consumption of contaminated food and low prevalence of oocysts due to scarcity of felines. PMID- 1412650 TI - Nutritional status of children with schistosomiasis mansoni in two different areas of Machakos District, Kenya. AB - A possible association between nutritional status and Schistosoma mansoni infection or morbidity was investigated by comparing anthropometric indices among 362 children from 3 primary schools in Machakos District, Kenya. Matithini was a prosperous school in an area (Kangundo) of moderate intensity of schistosome infection but low associated morbidity. A second area (Kambu) showed more severe schistosome-associated morbidity: in this area, Kitengei school was prosperous and with high intensities of schistosome infection, while Misuuni school was less prosperous and with low intensities of infection. Nutritional status was assessed by measurement and appropriate standardization of height, weight and skinfold thickness and by questionnaires concerning diet. Children in Kangundo were better nourished than those in Kambu. Within Kambu, children from Misuuni showed low mean skinfold thickness and low mean weight-for-height ('wasting'): this was associated with a lack of dietary variety and of intake of animal products. In contrast, those from Kitengei showed low mean height-for-age ('stunting'). The relationship between intensity of schistosome infection and nutritional indices, although significant, was complex and not readily interpretable. However, intensity of infection was also correlated with hepatomegaly, which was more clearly related to nutritional status. Depending on the school, children with hepatomegaly were significantly more stunted and/or wasted than those without, and had less variety in their diet. Possible reasons for the observed associations are discussed and, of various possibilities, the hypothesis is suggested that schistosome-associated morbidity leads to a subsequent nutritional defect. This hypothesis can now be tested by appropriate intervention studies. PMID- 1412651 TI - Estimation of the number of cases of schistosomiasis in a country: the example of Cameroon. AB - An estimate of the number of schistosomiasis infections in Cameroon was based on a statistically representative national prevalence survey carried out in the entire country. The number of cases of infection by Schistosoma haematobium was estimated to be 393,900, and 419,600 for S. mansoni, a total of 813,500. Taking into account the dual infections the total number of cases was 719,100 (95% confidence interval: 392 900-1 027,800). A current World Health Organization estimate extrapolating from the results of limited epidemiological surveys showed 2,239 591 cases for Cameroon, an estimate 3.1 times higher than the more accurate estimate based on the national survey. Schistosomiasis being a focal disease, prevalences observed in limited foci are not representative of regional prevalences. Prevalence survey data in the literature are biased toward reporting only positive results. Therefore extrapolations made on limited surveys may lead to an overestimation of the number of cases of schistosomiasis. PMID- 1412652 TI - A community trial of ivermectin for onchocerciasis in Sierra Leone: clinical and parasitological responses to four doses given at six-monthly intervals. AB - Clinical and parasitological responses were studied in villagers receiving all 4 doses of treatment, at 6-monthly intervals, in a placebo-controlled community trial of ivermectin for onchocerciasis in Sierra Leone. Skin microfilarial loads were markedly lowered by ivermectin throughout and there were reductions in the severity, but not the prevalence, of skin lesions. Markers of general health and the prevalences of itching, Onchocerca nodules and visual loss were not significantly reduced during the study period. Despite our inability to demonstrate obvious clinical benefit, treatment with ivermectin was well accepted throughout the study. Simple clinical measures for evaluating the short to medium term impact of the mass distribution of ivermectin on populations with onchocerciasis need further development. PMID- 1412654 TI - Adverse events following mass ivermectin therapy for onchocerciasis. AB - The Achi community of south-east Nigeria was given mass ivermectin therapy to control endemic onchocerciasis. 7556 subjects (75.6% of those eligible) were dosed. 992 patients (13.1%) complained of adverse effects, mostly within one week of dosing. Adverse events were mainly of the Mazzotti type. Exacerbation of pruritus (71.2%), oedema (47.4%), headache (46.4%), and worsening of rash (24.4%) were the most common. In 962 subjects (97%), adverse events were mild and did not prevent work. Two patients suffered severe sustained postural hypotension. The incidence of adverse events was greater in villages with a high load of microfilarial infection. PMID- 1412653 TI - Ivermectin does not reduce the burden of itching in an onchocerciasis endemic community. AB - Degrees of itching were estimated before and for 6 months after a fourth dose of ivermectin or placebo was given to 97 subjects in Sierra Leone. There was no reduction in itching attributable to ivermectin at any stage, but there were non significant increases in the prevalence, severity and localization of itching within the first 2 months after ivermectin compared to placebo. We also found that cell-mediated immune responses to Onchocerca volvulus were significantly increased 4 weeks after a single dose of ivermectin compared to before treatment. A temporary reversal of the state of immunosuppression in people with onchocerciasis may counterbalance the reduction in skin microfilarial loads following ivermectin, with no consequent reduction in itching. The lack of effect of ivermectin on itching, a major symptom of onchocerciasis, while disappointing, need not detract from the success of mass distribution programmes. PMID- 1412655 TI - Long-term suppression of microfilaraemia following ivermectin treatment. AB - Lymphatic filariasis has been difficult to control until recently because of the lack of a suitable drug for treatment. Ivermectin has proven safe and effective at reducing levels of circulating microfilariae. However, the apparent need to administer the drug every 6 to 9 months to keep microfilaraemia levels sufficiently suppressed to reduce transmission has been a major drawback to using ivermectin in community-based intervention programmes. In a study conducted in Haiti, we have found that high doses of ivermectin suppress microfilaraemia levels for 2 years. Our findings suggest that a single dose of ivermectin can reduce transmission of lymphatic filariasis for extended periods of time, thus eliminating the need for costly biannual treatment. PMID- 1412656 TI - Ivermectin treatment of loiasis. PMID- 1412657 TI - A rare case of mixed cystic and alveolar hydatidosis. PMID- 1412658 TI - Ivermectin therapy in chronic strongyloidiasis. PMID- 1412659 TI - Detection of circulating antigens in human trichinellosis. AB - A 'sandwich' enzyme-linked immunosorbent assay was established to detect circulating antigens of Trichinella spiralis in human sera, its sensitivity and specificity was evaluated using 4 antigens (Trichinella spiralis, Trichuris trichiura, Dirofilaria immitis and Ascaris suum), and it was found to be sensitive and specific for T. spiralis antigen. Samples of 347 individuals with suspected trichinellosis, who had eaten incompletely cooked bear meat containing larvae of T. spiralis, were examined. Among individuals showing clinical symptoms, circulating antigens were detected in 29.9%, and the prevalence of antibodies was 18.9%. Among individuals lacking clinical symptoms, antigens were detected in 21.4% and antibodies in 5.0%. It was concluded that detection of circulating antigens was more useful for making diagnoses than measurement of specific antibodies. PMID- 1412660 TI - Sero-epidemiological studies of respiratory syncytial and adenoviruses in children in Ibadan, Nigeria, 1985-1988. AB - Retrospective and prospective serological surveys to determine the prevalence of respiratory syncytial virus (RSV) and adenovirus (ADV) infections in children with respiratory diseases were carried out from 1985 to 1988 at the University College Hospital, Ibadan, Nigeria. 306 sera from subjects between 3 months and 12 years old were assayed by complement fixation test for antibodies to both viruses. Second samples were available from 42 of the subjects for antibody conversion testing. The rate varied with age, period of the year and virus. Overall prevalences of 23.5% and 18.3% were obtained for RSV and ADV respectively. 2.6% of the subjects had antibodies to both viruses. Among 42 paired samples tested, 61.9% and 33.3% showed positive antibody conversion to RSV and ADV respectively. Although there was evidence of active circulation of both viruses throughout the year, infection with RSV was higher from September to January, while ADV infection was significantly higher during February and March. Antibody prevalence to both viruses increased with age up to a peak of 39.1% for RSV in children 5-6 years old and 32% for ADV in children 3-4 years old. None of the subjects aged 10 years and above was positive for both viruses. Both RSV and ADV are important agents of acute respiratory infection in children in Nigeria. PMID- 1412661 TI - Tropical spastic paraparesis associated with HTLV-1 in Egypt. PMID- 1412662 TI - The slim disease in African patients with AIDS. AB - Ten unselected African patients infected with human immunodeficiency virus (HIV) and with slim disease were evaluated using physical examination, anthropometric measurements, Karnovsky performance score, and muscle biopsy. All had marked weight loss (36.8 +/- 10.8%) with extreme fatigue, marked diffuse wasting with significantly decreased circumferences of arms, thighs and calves (P < or = 0.002), and a low Karnovsky performance score (range 30-70). Mild to moderate motor deficit (in 9/10 patients) contrasted with the major amyotrophy. Chronic diarrhoea (in 7/10) and/or prolonged fever (in 7/10) were always associated with the amyotrophy. Atrophy of muscle fibers was the main finding of muscle biopsy. Only 5 patients met the CDC criteria for the 'HIV wasting syndrome'. We conclude that slim disease, which is highly suggestive of the acquired immune deficiency syndrome (AIDS) in Africa, is a condition associated with chronic diarrhoea and/or prolonged fever, that encompasses the 'HIV wasting syndrome' sensu stricto and probably other debilitating diseases associated with AIDS, such as tuberculosis. PMID- 1412663 TI - Serological response to tetanus toxoid: a field study in Pondicherry, India. AB - To study the serological response to various doses of tetanus toxoid given to pregnant women, 320 samples of blood obtained from 173 pregnant women were analysed using the indirect haemagglutination technique. Two doses of toxoid were necessary to achieve protective titres in women who were previously unimmunized. The antibody levels appeared to persist for up to 4 years. During a subsequent pregnancy, a single booster dose of toxoid was sufficient to raise the titres adequately for protection. These findings are in accordance with the immunization programme followed for prophylaxis against tetanus among pregnant women. PMID- 1412664 TI - Causes of conjunctivitis and keratoconjunctivitis in Karachi, Pakistan. AB - The causes of conjunctivitis and keratoconjunctivitis in 388 patients who attended eye casualty departments in Karachi, Pakistan, during a 5 month period were investigated. Most of these infections were diagnosed as adenovirus (291, 75%) or bacterial (71, 18.3%). Of the remainder, 9 cases (2.3%) were caused by herpes simplex virus and 7 (1.8%) by Chalmydia trachomatis. There was no evidence of typical active trachoma in this urban population. Bacteria or Candida albicans were also grown from 44 of the adenovirus cases (15%). Many of the bacteria grown from eyes in this study were resistant to antibiotics, probably because of inadequate and/or inappropriate self-medication with antibiotics in this community. PMID- 1412665 TI - First fatal human case of Rift Valley fever in Madagascar. PMID- 1412666 TI - A cluster of tick-borne infections: association with military training and asymptomatic infections due to Rickettsia rickettsii. AB - During the spring of 1989, 86 members of a military unit from the state of Maryland, USA, participated in two-week-long training manoeuvres in the states of Arkansas (location FC) and Virginia (location FAPH). Acute febrile illnesses due to infections with two tick-borne pathogens, Rickettsia rickettsii and Ehrlichia sp., were confirmed serologically in 2 initial cases who were admitted to the hospital. A seroepidemiological investigation among unit members found an additional 17 of 109 individuals (16%) with elevated post-exposure indirect immunofluorescent antibody (IFA) titres to R. rickettsii (16 cases) and/or E. canis (2 cases). The seropositivity rate of personnel who trained at FC was 38% (15 of 40), compared to only 13% (4 of 31) and 8% (3 of 38) of personnel who trained at FAPH or who did not train in the field, respectively (P < 0.001). Seropositivity was associated with symptoms suggestive of a tick-borne illness. Only 4 (22%) and 6 (33%) of the 18 personnel seropositive for R. rickettsii reported an erythematous or petechial type of rash or a febrile illness, respectively, within 4 weeks of exposure; 5 of 18 (28%) personnel infected with R. rickettsii reported no symptoms and only 8 of 18 (44%) received medical treatment. Mild infections with R. rickettsii, or a closely related spotted fever group agent, may have accounted for the high infection rate experienced by this group. PMID- 1412667 TI - Twenty-five years of blackfly control in a localized moist forest area of Cameroon: a review. AB - The high number of blackfly bites in a moist forest area of Cameroon, around the Sanaga river, was causing considerable nuisance and had led to a local ground based larval control campaign. We have reviewed the 25 years of almost uninterrupted weekly larvicide applications in this area and emphasized the problems related to application difficulties, environmental pollution and blackfly resistance to the insecticides. Although the number of larvicidal compounds readily available is now limited, the future of blackfly control at this site does not seem to pose real technical difficulties because of its economic importance (hydroelectric dam) and the progress made in the fields of resistance management, search for new insecticide molecules and development of new control methods. PMID- 1412668 TI - Infestation by Auchmeromyia senegalensis as a consequence of the adoption of non nomadic life by Pygmies in the Congo Republic. PMID- 1412669 TI - Some aspects of traditional birth attendants' practice in a rural area in Tanzania. AB - As a pre-intervention study to improve the safety of the practice of traditional birth attendants, all 29 attendants in one rural area in Tanzania were interviewed, using a pre-tested questionnaire seeking information on the instruments used, care of the umbilical cord, and how they dealt with problem cases. The results are presented and discussed in this paper. PMID- 1412670 TI - Stunting, intestinal parasitism and the home environment. PMID- 1412671 TI - A mini-stirrer for preparing antigen/adjuvant emulsions. PMID- 1412672 TI - 'Entamoeba histolytica' is a complex of two species. PMID- 1412673 TI - The works of Frideric Bolling--an early British-Danish relationship. PMID- 1412674 TI - Is the deferred-donor notification process effective? PMID- 1412675 TI - A survey of hepatitis B surface antigen-positive blood donors: degree of understanding and action taken after notification. AB - All blood donors in the United States are tested for hepatitis B surface antigen (HBsAg) upon donation; if the test result is positive, the primary method of notification is by letter. To assess the effectiveness of this notification methods in stimulating HBsAg-positive donors to seek medical care and take preventive measures, 54 donors who tested HBsAg-positive on donation at the American Red Cross Blood Services. Atlanta Region, from January 1987 to July 1989 were interviewed. Thirty-nine donors (72%) had sought medical care after notification; the only motivating factor was that the letter told the donor to consult with his or her physician. Compared with donors who did not seek medical care, donors who did so were more likely to understand that the blood test was abnormal or that they were infected, and they were more likely to understand how hepatitis B virus is transmitted and that a vaccine is available. The differences were not significant, however. Of those donors who sought medical care, less than half received appropriate recommendations for protection of contacts, and of those who did, only one-third received prophylaxis. In-person and telephone interviews with donors, revision of the notification letter, and hepatitis B education programs targeted at medical care providers are suggested. PMID- 1412676 TI - Human immunodeficiency virus infection due to clotting factor concentrates: results of the Seroconversion Surveillance Project. AB - From 1987 to the present, the Seroconversion Surveillance Project has provided the means by which to monitor the risk of transmission of human immunodeficiency virus (HIV) by clotting factor concentrates. One hundred thirty-one hemophilia treatment centers in the United States are contacted regularly, and data on HIV testing of patients are collected. To date, 4366 (46.0%) of 9496 patients have been reported to be seropositive, and 37 new seroconversions have been identified. Nine of these have met the Centers for Disease Control criteria for seroconversion while the patient was taking factor concentrate. None of the nine seroconversions were due to concentrates that had been treated to inactivate viruses and made from plasma that had been tested for HIV antibody. These results indicate that there is a high prevalence of seropositivity in affected patient groups, but that the risk of HIV infection from currently available clotting factor concentrates is extremely low. PMID- 1412678 TI - Pretransfusion incubation of apheresis platelets at 37 degrees C improves posttransfusion recovery. AB - The effect of brief 37 degrees C pretransfusion incubation of apheresis platelets (n = 25) was studied in 14 allogenic bone marrow transplant recipients (5 children, 9 adults). Apheresis platelets were collected on a cell separator, divided in two aliquots, and stored 1 to 5 days at 22 degrees C during agitation. One aliquot was incubated at 37 degrees C for 1 hour before transfusion, and the other was transfused as a paired control. When the patient's peripheral platelet count fell below 30 x 10(9) per L, one aliquot was transfused. The other aliquot was transfused the following day. Each patient received the two aliquots in random order. Corrected count increment (CCI) at 1 hour after transfusion of 37 degrees C incubated platelets was 12.2 +/- 9.5 (mean +/- SD) compared to 7.5 +/- 5.4 for paired control platelets (p < 0.05). CCIs the next day were 4.4 +/- 6.1 and 2.4 +/- 2.7, respectively (not significant). It can be concluded that 37 degrees C incubation of apheresis platelets improves posttransfusion CCI. PMID- 1412677 TI - Thrombotic thrombocytopenic purpura: outcome in 24 patients with renal impairment treated with plasma exchange. Canadian Apheresis Study Group. AB - The Canadian Apheresis Study Group recently completed a randomized clinical trial involving 102 patients with thrombotic thrombocytopenic purpura (TTP), in which treatment with plasma infusion and treatment with plasma exchange were compared. Thirty-three other patients were ineligible or refused to be randomly assigned in the trial. Of the 33 patients, 24 were assessed as ineligible because they would be unable to tolerate the fluid input that would occur if they were randomly assigned to receive plasma infusion. All 24 patients had oliguria and elevated creatinine and/or blood urea nitrogen level. These 24 patients were treated with acetylsalicyclic acid, dipyridamole, and plasma exchange according to the standardized protocol defined in the trial. Blood for tests of factors possibly involved in the pathogenesis of TTP was drawn before exchange and at intervals during and after exchange. The mean platelet count before exchange was 35.5 x 10(9) per L. In 12 of the 24 patients, the platelet count reached 150 x 10(9) per L or greater by 7 days after the initiation of plasma exchange. Three patients responded partially, in that their platelet count increased to at least twice that at presentation, but remained below 150 x 10(9) per L. One patient died during the first week. Of the eight other patients who experienced treatment failure at the 7-day assessment point, six subsequently responded, four while continuing to receive plasma exchange and two after plasma exchange had been discontinued. Of the 15 patients who either responded fully or responded partially by the end of the first cycle, all survived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1412679 TI - Anti-idiotypic antibody to T-cell receptor in multiply transfused patients may play a role in resistance to graft-versus-host disease. AB - Most patients who receive multiple blood or platelet transfusions do not develop graft-versus-host disease (GVHD) in spite of the transfusion of donor white cells -cells that are capable of engraftment and subsequent GVHD. The object of this study was to search for the factors responsible for resistance to GVHD in such patients. Some sera from patients who have received multiple platelet transfusions inhibit the proliferation of alloreactive T-cell clones that function as an in vitro model of donor-derived proliferating T cells recognizing recipient alloantigens. The humoral factor in such sera was capable of binding to the T-cell clones, but not to stimulator cells. Further analysis revealed that the humoral factor in such sera was IgG, which specifically bound to membrane molecules of the T-cell clones. The antibody competed with WT31, a monoclonal antibody (MoAb) to T-cell receptor (TCR), in binding to TCR of the T-cell clones. It did not compete with CD3 or CD2 MoAb. These observations strongly favor the view that the antibody against TCR exists in the sera of multiple transfusion recipients. It is suggested that the TCR antibody binds to TCR of the T-cell clones, thus blocking the interaction of the T-cell clone with alloantigens of stimulator cells and resulting in inhibition of the proliferation of T-cell clones. Furthermore, in view of T-cell clone-specific binding of the antibody in sera, it might be concluded that the antibody is anti-idiotypic. PMID- 1412680 TI - Five-day storage of platelets in a non-diethylhexyl phthalate-plasticized container. AB - A non-diethylhexyl phthalate (DEHP)-plasticized blood bag for 5-day storage of random-donor platelet concentrates has been developed. The plastic bag is composed of polyvinylchloride plastic with a butyryl trihexyl citrate plasticizer. The suitability of this plastic for the storage of platelet concentrates for use in clinical transfusion practice was evaluated. In vitro storage studies showed no significant differences at Day 5 for a series of in vitro assays (test plastic vs. control plastic) including pH (7.31 vs. 7.44), lactate dehydrogenase discharge (21.8 vs. 17.1%), pO2 (103 vs. 120 torr), osmotic recovery (52 vs. 57%), and morphology score (527 vs. 516). For paired radiolabeled recovery and survival data from autologous blood donors, results showed equivalence between the test plastic and two control plastics. A small but significant difference between test and control plastics in regard to survival was found by using a linear computer model, but not with a gamma function (multiple-hit) model. For paired transfusions to thrombocytopenic patients, the corrected count increments at 1 to 4 hours (test vs. control) were 13,534 versus 15,494 (p > 0.05, NS). Similar results were seen for corrected count increments determined at 12 to 24 hours. It can be concluded that platelets stored in the test plastic are acceptable for use in clinical practice. PMID- 1412681 TI - A randomized trial on the efficacy of an autologous blood drainage and transfusion device in patients undergoing elective knee arthroplasty. AB - The purpose of the study reported here was the determination of the efficacy of a postoperative autologous blood drainage and transfusion device in reducing allogeneic red cell requirements in patients undergoing elective knee arthroplasty. The study was a randomized controlled trial with adult patients undergoing unilateral elective arthroplastic knee surgery. Patients underwent suction drainage, attached to an autologous blood drainage and transfusion device, or standard suction drainage. Allogeneic red cells were given according to strict transfusion guidelines based on blood loss and postoperative hemoglobin values. Outcome measures included the mean number of allogeneic red cell concentrates required and the number of patients in each group who required no transfusion. Patients assigned to standard suction drainage had a mean allogeneic red cell utilization of 1.2 units (SD 1.0), as compared to a mean of 0.4 units (SD 0.8) in the group undergoing drainage with the autologous blood drainage and transfusion device (p = 0.0007). The percentage of patients not requiring allogeneic red cells was significantly higher in the latter group (74.3% vs. 32.5%; p = 0.002). The postoperative drainage and transfusion device was efficacious in reducing the amount of allogeneic red cells required by patients undergoing knee arthroplasty, and its use resulted in a 42 percent reduction in the number of patients requiring allogeneic transfusion. PMID- 1412683 TI - Low-temperature storage of bone marrow in nitrogen vapor-phase refrigerators: decreased temperature gradients with an aluminum racking system. AB - Large temperature gradients may exist in nitrogen vapor-phase refrigerators. Cryopreserved cells stored at higher levels may be considerably warmer than those stored closer to the liquid nitrogen reservoir. To decrease this temperature gradient, racking systems constructed of aluminum were placed in marrow storage refrigerators. The higher heat conductivity of aluminum resulted in a vapor-phase temperature gradient of only 5.9 degrees C at 22.5 inches above the liquid, as compared to the gradient of 86 degrees C seen with steel frames in a similar refrigerator. Temperature fluxes were minimal with lid opening or nitrogen filling. The thicker frame size and loss of the lowest storage level resulted in a storage capacity 63 percent of that achievable with steel frames and liquid immersion. Consumption of nitrogen was estimated to be 174 to 220 percent of the static usage in this model of refrigerator with 6 inches of nitrogen, but comparable to the consumption expected with full immersion of the racking system, regardless of frame construction. These data demonstrate the feasibility of achieving very low, stable, cryogenic temperatures in a vapor-phase refrigerator. PMID- 1412682 TI - Feasibility and success of a single-donor red cell program for pediatric elective surgery patients. AB - Although the risks of allogeneic blood transfusions are small, it is wise to limit donor exposure whenever possible. A program has been developed in which one donor provided all red cell (RBC) units for each patient awaiting elective surgery. Patients were mostly children who were ineligible for autologous blood donation. Seventy-three patients and 115 donors (mostly parents) entered the program. Of the 115 donors, 90 (78%) were eligible to participate and 25 (22%) were ineligible; 21 were ineligible because of RBC incompatibility. For each of the 73 patients, one eligible donor was selected to donate all RBC units. Preoperative RBC orders were 1 to 2 units for 41 patients and > or = 3 units for 32 patients. Of the 73 donors, 58 (79%) gave all RBC units ordered; 15 (21%) failed to complete all donations, but only 1 because of anemia (hematocrit < 33% [0.33]). Of 73 patients entered, 46 (63%) underwent transfusion, and 27 (37%) did not. Of 46 patients transfused, 38 (83%) received only single-donor RBCs. Thus, the RBC needs of nearly all pediatric elective surgery patients were provided by a single donor for each patient. Single-donor blood programs should be considered for elective surgery patients who are ineligible for autologous blood donation and who would otherwise be exposed to multiple donors. PMID- 1412684 TI - Modulation of fibrinogen content in cryoprecipitate by temperature manipulation during plasma processing. AB - In routine blood bank production of single-donation cryoprecipitate, the introduction of a 16-hour hold at 4 degrees C, with the frozen plasma units packed into polystyrene containers, resulted in plasma prethaw temperatures of -4 degrees C to -8 degrees C. This in turn resulted in cryoprecipitate fibrinogen levels that were 214 percent of those obtained when units were thawed immediately after removal from -30 degrees C storage. In scale-model production of factor VIII concentrate, plasma warmed from -30 to -10 to -15 degrees C over 18 hours before pooling and thawing yielded cryoprecipitate fibrinogen levels that were 66 percent of those found in plasma warmed to -2 to -5 degrees C over the same period. Processing -30 degrees C plasma without a warming period led to cryoprecipitate fibrinogen levels that were 40 percent of those obtained from plasma warmed to -2 to -5 degrees C. These differences were accentuated after purification of the cryoprecipitates to an intermediate-purity factor VIII concentrate. These results suggest that simple modifications in production methods allow the fibrinogen content of cryoprecipitate to be tailored to specific uses. PMID- 1412685 TI - Risk factors associated with hepatitis B or C markers or elevated alanine aminotransferase level among blood donors on a tropical island: the Guadeloupe experience. AB - Donated blood is currently screened for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis C virus (anti-HCV), and alanine aminotransferase (ALT) levels to prevent posttransfusion hepatitis. A prospective study of 2368 blood donors was carried out in Guadeloupe (French West Indies) with a view to determining the risk factors associated with serologic abnormalities. Blood donors included in the study had to complete a questionnaire. Statistical analysis was performed on the data thus obtained: 571 donations (24%) were positive for at least one of the four analyzed markers. The results were that 3.2 percent were positive for HBsAg, 22 percent for anti-HBc, and 0.8 percent for anti-HCV, and 1.4 percent had ALT > or = 45 IU per L. A good correlation was found between anti-HCV and elevated ALT. Transfusion history and two socioeconomic categories (working class, military personnel) were found to be risk factors. Other risk factors were lifelong residence in Guadeloupe (with risk increasing with the number of years), birthplace and current residence in the southern part of the island, and the existence of gastrointestinal discomfort unrelated to viral hepatitis (odds ratio = 2.98). The results of this study illustrate the difficulty of implementing a preventive policy against posttransfusion hepatitis in a tropical area. The unique epidemiologic situation of Guadeloupe as regards hepatitis B virus has led to more restrictive criteria for the acceptance of blood donors. PMID- 1412686 TI - The effects of blood transfusion on serum ferritin, folic acid, and cobalamin levels. AB - Thirty patients with anemia of various causes received packed red cell transfusions. To evaluate the influence of blood transfusion on the serum levels of different nutrients, serum ferritin, folate, and cobalamin levels were determined before and 2, 2 to 4, 5 to 7, 8 to 10, and 11 to 14 days after blood transfusion. No significant change was found in these levels before or at any time after blood transfusion. Blood transfusion exerted little effect on the serum levels of ferritin, cobalamin, or folate. Moreover, if the blood for testing was drawn 1 to 14 days after transfusion, nearly all cases of nutritional deficiency anemia could have been diagnosed without the influence of blood transfusion. PMID- 1412688 TI - Staphylococcus epidermidis bacteremia from transfusion of contaminated platelets: application of bacterial DNA analysis. AB - Septicemia is a rare complication of platelet transfusion. A case is reported of transfusion-associated septicemia in a 66-year-old man who received a 10-unit pool of platelets. During transfusion, he experienced rigors, wheezing, dyspnea, and fever. A total of four blood cultures drawn 10 and 36 hours after discontinuation of the transfusion grew Staphylococcus epidermidis. Culture of the residual platelet pool yielded S. epidermidis with a colony count of 10(5) organisms per mL. Strain identity of all four blood isolates and the platelet pool isolate was confirmed by gel electrophoresis of EcoRI and HindIII restriction digests of whole-cell DNA. There have been 31 prior reported cases of platelet transfusion-associated septicemia, of which 9 have been caused by coagulase-negative staphylococci. Systemic reactions to platelet transfusions should prompt consideration of transfusion-associated bacteremia as the cause. PMID- 1412687 TI - Diagnosis of transfusion-associated graft-versus-host disease by genetic fingerprinting and polymerase chain reaction. AB - A patient with Hodgkin's disease (clinical stage IIIB) received chemotherapy and total nodal irradiation. After the transfusion of filtered packed red cells, this patient developed transfusion-associated graft-versus-host disease (TA-GVHD). The genetic fingerprint of the patient's peripheral blood lymphocytes (PBLs) differed completely from that of her other body tissues. Normally, after transfusion, only the patient's own genetic fingerprints are observed in the PBLs, as exemplified in more than 10 control cases in which the transfused blood had not been filtered before transfusion. No signal bands corresponding to those of the blood donor could be demonstrated in samples of the patient's tissue DNA. Moreover, chimerism was detected in the hybridization pattern of the patient's PBLs on the ninth day after the onset of symptoms. Polymorphic simple repeats in the HLA-DRB gene after amplification by polymerase chain reaction were also investigated, which confirmed the fingerprinting results. The advantages of these methods for the diagnosis of TA-GVHD include the rapid and unequivocal diagnosis as well as the fact that there is no need for the relatives to be HLA typed. PMID- 1412689 TI - A prospective blood utilization review system. PMID- 1412690 TI - Iron for autologous blood donors needs more work. PMID- 1412691 TI - An anti-K apparently induced by Enterococcus faecalis in a 30-year-old man. PMID- 1412692 TI - Cold agglutinin autoimmune hemolytic anemia as a severe complication in B-cell acute lymphocytic leukemia. PMID- 1412693 TI - Hydrolysis of phosphate monoesters: a biological problem with multiple chemical solutions. AB - Formation of phosphate esters by kinases has long been recognized as an important process in biochemistry, but the reverse reaction, hydrolysis of phosphate esters by phosphatases, has attracted less attention. Recent work suggests that phosphatases are as important as kinases in regulatory processes, and that they constitute a diverse group of enzymes that utilize a variety of chemical means to accelerate phosphate ester hydrolysis. PMID- 1412694 TI - Fructose-bisphosphate aldolases: an evolutionary history. AB - Two mechanistically distinct forms of fructose-bisphosphate aldolase are known to exist. It has been assumed that the Class II (metallo) aldolases are evolutionary more primitive than their Class I (Schiff-base) analogs since the latter had only been found in eukaryotes. With the identification of prokaryotic Class I aldolases, we present here an alternative scheme of aldolase evolution. This scheme proposes that both aldolase classes are evolutionarily ancient and rationalizes the observed highly variable expression of both enzyme types in contemporary file forms. PMID- 1412696 TI - Ribonucleotide reductase: regulation, regulation, regulation. AB - Ribonucleotide reductase (RNR) catalyses the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. It is composed of two dissimilar subunits, R1, the large subunit containing the allosteric regulatory sites, and R2, the small subunit containing a binuclear iron center and a tyrosyl free radical. Recent isolation of the mammalian and yeast RNR genes has shown that, in addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. The mRNAs for both subunits are cell-cycle regulated and, in yeast, inducible by DNA damage. Yeast encode a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. This regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. PMID- 1412695 TI - Dual-specificity protein kinases: will any hydroxyl do? AB - Protein kinases are classified by the target amino acid in their substrates. Those protein kinases that phosphorylate hydroxyamino acids comprise two groups, the protein-tyrosine and protein-serine/threonine kinases, which, until recently, had been thought to be mutually exclusive. However, several new protein kinases have been discovered that, by the criterion of primary structure, would be classified as protein-serine/threonine kinases but which, surprisingly, are able to phosphorylate tyrosine residues. Even more surprising, there are reports of protein kinases that are capable of phosphorylating both tyrosine and serine/threonine residues. We review and discuss recent developments concerning these 'dal-specificity' protein kinases. PMID- 1412697 TI - Trimeric G proteins in Golgi transport. PMID- 1412698 TI - Chromatin condensation: does histone H1 dephosphorylation play a role? AB - In this article we describe three distinct biological systems where histone H1 phosphorylation is uncoupled from mitosis and highly condensed chromatin is enriched in dephosphorylated forms of H1: the amitotic macronucleus of Tetrahymena, terminally differentiated avian erythrocytes and sea urchin sperm. Each system offers informative contrasts to the idea that H1 hyperphosphorylation is causally related to mitotic chromosome condensation. Assuming that higher order chromatin folding is primarily driven by electrostatic interactions between H1 and DNA, an alternative model is presented for the role of H1 phosphorylation in chromatin condensation. PMID- 1412699 TI - Inositol lipids in cellular signalling mechanisms. AB - At the opening of the 1980s, two camps vigorously contested whether receptor stimulated inositol lipid hydrolysis was a transmembrane signalling reaction that brought about an elevation of cytosolic [Ca2+] or simply a frequent, but unexplained, response of many stimulated cells to a stimulated elevation of cytosolic [Ca2+]. Since 1984, this discussion has been replaced by intensive work that is well on the way to providing a detailed description of the complex set of signalling pathways initiated by phosphatidylinositol 4,5-bisphosphate hydrolysis to form the second messengers inositol 1,4,5-trisphosphate and 1,2 diacylglycerol. In addition, it has been realized that cells closely regulate their levels both of a novel family of 3-phosphorylated inositol lipids and of a large number of water-soluble inositol polyphosphates; the definition of the functions of these molecules will be a job for the 1990s. PMID- 1412700 TI - The cell cycle then and now. AB - In the last few years a general model of cell cycle control has been established for all eukaryotic cells. Experiments from a variety of organisms and from a variety of experimental approaches have identified a protein kinase and its unstable regulatory subunit as the activator of mitosis; related molecules seem to be involved in the activation of chromosome replication. The identification of the biochemical components of these important regulatory pathways is providing several new insights into homeostatic and developmental control mechanisms in higher organisms. PMID- 1412701 TI - Hemopoietic regulators. AB - The production and maturation of blood cells from the eight major blood cell lineages is a complex and continuous process, which is largely controlled by specific glycoprotein hemopoietic regulators. These regulators also control the functional activity of the blood cells through eliciting a diverse set of intracellular responses initiated by a regulator-specific membrane receptor. Twenty of these regulators have now been characterized, and their mass production has led to four already being licensed for clinical use in disease states involving subnormal blood cell formation. PMID- 1412702 TI - The molecular and biochemical basis of Duchenne muscular dystrophy. AB - Duchenne and Becker muscular dystrophy (DMD, BMD) have both been clinically recognized for over 100 years, yet throughout much of that time nothing beyond clinical evaluation and supportive care during the disease course was available to patients. The identification of the molecular basis of DMD/BMD in 1986 paved the way for extensive progress toward the understanding, diagnosis and treatment of this disease. PMID- 1412703 TI - Protein engineering. AB - Ten years of protein engineering have seen the synthesis of novel therapeutic agents and the analysis of the structure, activity, specificity, stability and folding pathways of proteins. It is hoped that protein engineering will eventually lead to the design of novel catalytic sites on either novel or existing proteins. PMID- 1412704 TI - Microtubule motors: many new models off the assembly line. AB - A far greater variety of microtubule-based motors populate the interior of most eukaryotic cells than was ever imagined, and the inventory of these proteins is growing each year. The discovery of new motors, however, has raised many questions of how cells use their arsenal of force-generating machines. The ability to apply genetics, bacterial expression, biochemistry and in vitro motility assays to study motor proteins provides new opportunities for examining these problems at a molecular level. PMID- 1412705 TI - The retinoblastoma protein and the regulation of cell cycling. AB - Increasing attention has been focused on how the retinoblastoma (RB) protein regulates cell growth. Recent evidence indicates that it is a substrate for phosphorylation by cyclin-dependent kinase-cyclin complexes and suggests that this phosphorylation modulates the ability of this protein to regulate transit through the cell cycle, perhaps in its G1 phase. PMID- 1412706 TI - Now you see it, now you don't: the Golgi disappearing act. PMID- 1412707 TI - Does Fourier-transform infrared spectroscopy provide useful information on protein structures? PMID- 1412708 TI - Oxygen and the connective tissues. AB - Avascular connective tissues (cartilage, discs, cornea) change with maturation and aging, particularly in large animals, where diffusion paths are longest. It is suggested that the changes in such tissues are responses to increasing difficulties in obtaining oxygen. Two almost identical structural polymers are made in these tissues: chondroitin sulphate, which requires large amounts of oxygen for biosynthesis and keratan sulphate, which requires relatively little. The observed balance of these polymers in the tissue is proposed to depend on the control of biosynthesis by the ambient oxygen tension, and/or selective breakdown. PMID- 1412709 TI - A novel zinc finger coiled-coil domain in a family of nuclear proteins. PMID- 1412710 TI - A neurofilament-specific sequence motif. PMID- 1412711 TI - Protein phosphorylation and LHCII structure. PMID- 1412712 TI - Nuclear targeting sequences. PMID- 1412713 TI - Excavations into the active-site gorge of cholinesterases. AB - Acetyl- and butyrylcholinesterase (ACHE, BCHE) from evolutionarily distant species display a high degree of primary sequence homology and have biochemically similar catalytic properties, yet they differ in substrate specificity and affinity for various inhibitors. The biochemical information derived from analyses of ACHE and BCHE from human, Torpedo, mouse, and Drosophila, as well as that from the recombinant forms of their natural variants and site-directed mutants, can currently be re-examined in view of the recent X-ray crystallography data revealing the three-dimensional structure of Torpedo ACHE. The picture that emerges deepens the insight into the biochemical basis for choline ester catalysis and the complex mechanism of interaction between cholinesterases and their numerous ligands. PMID- 1412714 TI - Cell membrane-associated mucins and their adhesion-modulating property. AB - A class of highly sialylated glycoproteins with very large mucin-like domains that protrude high above the plasma membrane have been shown to strongly reduce cellular adhesion. In normal epithelial cells, where the expression is restricted to the luminal side of the cell, these molecules may prevent inadvertent closing of the lumen as a result of weak, non-specific protein-protein interactions between opposite luminal membranes. In malignant tumors cellular polarization is often lost, which can lead to the entire cell surface being covered by these molecules. The resulting strongly reduced adhesion and immune recognition properties may play an important role during invasion and metastasis. PMID- 1412715 TI - Alloimmunization, memory, and the interpretation of crossmatch results for renal transplantation. PMID- 1412716 TI - The role of beta-2 microglobulin in temperature-sensitive and interferon-gamma induced exocytosis of HLA class I molecules. AB - The passage of MHC class I heavy chains through the exocytic pathway is promoted by association with beta 2 microglobulin (beta 2m). In order to analyze the structural basis of this phenomenon, processing and cell surface expression of HLA class I molecules have been investigated in the beta 2m null human melanoma cell line FO-1 transfected with either the human or mouse beta 2m genes. These natural structural variants of beta 2m display 30% amino acid sequence divergence. In comparison with a human beta 2m transfectant of the FO-1 cell line (designated FO-1H), FO-1 cells transfected with the mouse beta 2m gene (FO-1C) express HLA class I molecules that are processed with grossly altered kinetics and are present on the cell surface at reduced levels. The suboptimal expression of HLA class I heavy chains encoded by FO-1C cells reflects a defect in heavy chain stability since cell surface expression of HLA class I antigens was increased following incubation at 30 degrees C. The increased cell surface expression paralleled accelerated processing of HLA class I heavy chains by FO-1C cells. In contrast, no induction in either cell surface expression or processing of HLA class I heavy chains was observed for the beta 2m-negative FO-1 parent cell line, which remained HLA class I antigen null when cultured at 30 degrees C, or the FO-1H human beta 2m transfectant, which expressed equivalent levels of HLA class I antigens on the cell surface at 37 degrees C and 30 degrees C. Further up regulation of the temperature-sensitive induction of HLA class I antigen expression was accomplished by treatment of the FO-1C transfectant with interferon-gamma; this latter effect appears to be active at a posttranscriptional step for FO-1 cells since IFN-gamma was not as potent a transcriptional activator at 30 degrees C as it was at 37 degrees C. These results indicate that HLA class I heavy chains expressed by FO-1C cells are subject to temperature-sensitive and cytokine-inducible stabilization that increases their affinity for the structural variant of beta 2m and promotes exocytosis of the HLA class I heterodimer to the cell surface. Furthermore, beta 2m non-conformed MHC class I heavy chains undergo stabilization that is not associated with enhanced cell surface expression, indicating that the exocytosis of putative "empty" HLA class I antigens is a process dependent upon association with beta 2m. PMID- 1412717 TI - The prolongation of concordant hamster-to-rat cardiac xenografts by brequinar sodium. AB - Brequinar sodium (BQR) prevents cell proliferation by virtue of its inhibition of de novo pyrimidine biosynthesis. The immunosuppressive activity of BQR is highly effective in prolonging heart, liver, and kidney allograft survival in the rat. In these experiments, we have tested the ability of BQR to prevent the rejection of concordant cardiac xenografts. LEW inbred rats transplanted with heterotopic hamster hearts were treated orally with brequinar sodium as a single agent. The survival of the cardiac xenografts was significantly prolonged with a variety of treatment regimens. The most effective treatment was the daily oral administration of BQR at 3 mg/kg. At this level, the median graft survival was approximately 25 days. Four animals had hamster heart xenografts that functioned for more than 90 days. The prolonged survival of the xenografts was associated with relatively constant plasma drug levels of approximately 1 to 3 micrograms/ml and a marked suppression of IgM production. At rejection, there was a significant rise in IgM levels compared with those of recipients with stable xenografts. In vitro MLR responses were effectively inhibited by BQR, with an IC50 of 0.08 microgram/ml. The results of these experiments demonstrate that BQR is a new immunosuppressive agent that is highly effective as a single agent in prolonging the survival of hamster-to-rat cardiac xenografts. The prolonged xenograft survival is associated with effective suppression of rat antihamster antibody production, suggesting that brequinar sodium may be an important addition to multidrug immunosuppressive regimes designed to prevent B and T lymphocyte mediated immune responses. PMID- 1412718 TI - Evidence that long-term survival of concordant xenografts is achieved by inhibition of antispecies antibody production. AB - Antibody and complement have been shown to be of primary importance in the rejection of hamster heart xenografts by rats. Very high anti-hamster antibody titers were detected at the time of rejection of hamster hearts transplanted into untreated or T cell deficient rats. This study demonstrates a method of inhibiting this antibody production by pulse therapy with cyclophosphamide (CyP) and continuous cyclosporine treatment, resulting in a median survival of the hamster heart of greater than 100 days. Controls and CsA-treated rats reject the transplanted hamster heart in a median of 3 days. CyP as a sole therapy resulted in a median survival of 14 days. Prolonged CyP therapy when combined with CsA was associated with increased death among rat recipients due to infection. Antispecies antibody production was suppressed during CyP and CsA therapy and did not recur after cessation of CyP therapy. Cessation of CsA therapy at 60 and 100 days posttransplantation resulted in subsequent rejection of the xenografts (median survival after cessation of therapy of 11 and 19.5 days, respectively) and was associated with production of rat anti-hamster antibodies. PMID- 1412719 TI - The effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on ischemia-reperfusion-induced liver injury in rats. AB - This study was designed to clarify the effects of changes in liver tissue glutathione (GSH) concentration on postischemic liver injury together with the effects of gamma-glutamylcysteine ethyl ester (GCE), a prodrug of GSH, and GSH. Rats were pretreated with GSH (50 mg/kg, i.v.), or GCE (50 mg/kg, i.v.), or untreated. In each rat, liver was isolated, and liver mitochondria were prepared after 2 h of ischemia or 1 h of reperfusion following 2 h of ischemia. Mitochondrial function was measured polarographically. Liver adenine nucleotide concentrations were also determined using high-performance liquid chromatography. Liver tissue GSH, an oxidized form of glutathione (GSSG) concentrations, and activities of GSH peroxidase and GSSG reductase were determined enzymatically. Liver hypoxanthine and xanthine concentrations were determined by HPLC. Liver tissue concentration of lipid peroxide was measured. Leakages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and adenine nucleotides into the hepatic vein after reperfusion were also measured. Administration of GCE improved the recovery of mitochondrial function and maintained tissue GSH concentration concomitantly. Increases in liver lipid peroxide concentration after reperfusion, and leakage of liver cell enzymes and adenine nucleotides were mitigated by administration of GCE. Administration of GSH itself failed to maintain tissue GSH concentration and had no protective effects. From these results, it is concluded that in the postischemic process, free radical formation might be enhanced, and the radical scavenging system deteriorated. To enhance the radical scavenging system is a possible maneuver to prevent radical-related cell damage associated with reperfusion, because pharmacological reduction of breakdown of ATP to hypoxanthine and xanthine seems to be difficult. GCE maintained liver GSH concentrations and mitigated postischemic liver injury, concomitantly. Clinical use of GCE might be recommended. PMID- 1412720 TI - The effect of prostaglandin E1 on heart preservation. AB - The purpose of this study was to investigate the effect of prostaglandin E1 on rabbit heart preservation. The hearts were arrested with cardioplegia (CP) solution, followed by intracoronary infusion of Euro-Collins (E-C) solution. They were immersed in E-C solution at 4 degrees C for 9 hr, flushed with terminal warm CP solution, and reperfused with oxygenated Tyrodes' solution at 80 mmHg for 90 min. Eighteen rabbits (Kabushikigaishya BioTec Japanese white) were divided into 3 groups. Group I served as the control. In groups II and III, 200 ng/kg/min of PGE1 was given for 30 min before the heart was removed and 5 micrograms was added to the initial CP solution. In group III, 5 micrograms was also added to both E-C solutions and to the terminal CP solution. The values of CPK and LDH in the terminal CP solution and in the coronary effluent in groups II and III were lower, and coronary flow after reperfusion in group III was significantly greater at 5 min and from 60 min until the end of the experiment. Left ventricular maximum dP/dt at each end-diastolic pressure was significantly higher than control in groups II and III. The values of the wet/dry ratio of reperfused hearts in groups II and III were significantly lower than in the control. In conclusion, treatment with PGE1 before heart extraction and the addition of PGE1 to both E-C solutions and to the terminal CP solution contributed to superior left ventricular function after reperfusion, by improving preservation and reducing interstitial edema. PMID- 1412721 TI - The effects of long-term graft preservation and prostaglandin E1 on intraoperative hemodynamic changes in liver transplantation. A comparison between orthotopic and heterotopic transplantation in the pig. AB - The study aimed to compare the intraoperative hemodynamic changes during orthotopic liver transplantation (OLT) with those during heterotopic liver transplantation (HLT) after different durations of cold storage of the graft. The effect of prostaglandin E1 (PGE1) on these parameters was also studied. Sixty nine female Yorkshire pigs underwent either OLT (n = 32) or HLT (n = 37) with a graft stored for 2 hr (n = 31), 24 hr (n = 16), 48 hr (n = 7), or 72 hr (n = 15). In 16 transplantations in the various groups, PGE1 was given intravenously to both donor and recipient animals and it was added to the preservation and flushing solutions. Univariate nonparametric tests (Mann-Whitney and Wilcoxon rank-sum) were used for analysis of cardiac output (CO), mean arterial pressure (MAP), left and right ventricular minute work (LVMW, RVMW), pulmonary capillary wedge pressure (PCWP), and systemic and pulmonary vascular resistance (SVR, PVR), at different intervals during the operative procedure. For the three main variables--i.e., the type of transplantation, the use of PGE1, and the preservation time, multiple regression analysis was performed. During HLT, portal vein clamping lowered MAP and CO, while during the anhepatic phase in OLT, SVR increased and CO dropped. After recirculation of the graft, an increase in PVR and a decrease in SVR were found in both OLT and HLT. At different stages of the surgical procedure, longer graft storage time diminished CO and MAP (P less than 0.001), especially in OLT. PGE1 appeared to reduce the cardiovascular reserves needed to compensate the changes after recirculation of the graft. The observed differences in intraoperative hemodynamics between OLT and HLT can partly be attributed to differences in operative techniques. Extension of the graft preservation period resulted in poor cardiac performance, more so in OLT than HLT. The native liver in HLT might be able to metabolize the presumed myocardial depressant factors, released by the graft upon reperfusion. Prostaglandin E1 did not protect against the reperfusion syndrome. PMID- 1412722 TI - The outcome of pregnancy following renal transplantation--the experience of a single center. AB - Many centers still recommend avoidance of pregnancy after renal transplantation because of fears for the safety of both mother and fetus. These fears are in part based on a lack of information concerning the effects of newer immunosuppressive drugs such as cyclosporine on the course and outcome of pregnancy. The present study examines the experience of first pregnancies following renal transplantation in a single center, with emphasis on the role of CsA. Data on the first pregnancies of 22 women transplanted between 1977 and 1988 were studied. The mean age of patients at the time of transplant was 23.4 +/- 3.1 years and interval from transplant to pregnancy was 34.5 +/- 24.5 months (range 1-75 months). Twelve patients received CsA alone or in combination with other immunosuppressives, while the remaining 10 patients received azathioprine and prednisone. Mean serum creatinine fell progressively during pregnancy in both CsA and azathioprine-treated mothers. Mean CsA dose rose during pregnancy while mean CsA blood concentration fell during the 2nd trimester (P = 0.042). The gestation period ranged from 27 to 40 weeks (35.5 +/- 3.3) with 14 pregnancies ending prematurely prior to 37 weeks. Thirteen deliveries occurred by Caesarian section. Hypertension complicated 10 pregnancies. Birth weight correlated directly with both maternal weight gain (r = 0.57; P less than 0.02) and gestational age (r = 0.9; P less than 0.01). Ten of 23 offspring were below the 10th percentile for weight. Mean birth weight ranged from 0.72 to 3.7 kg (2.3 +/- 0.84 kg). The mean birth weight and gestational age of children born to mothers taking CsA were lower than those in azathioprine treated mothers but these differences were not statistically significant. Successful pregnancy is possible following renal transplantation, although there is a high rate of prematurity, low birth weight, and intrauterine growth retardation. CsA dose requirements may be increased. Maternal risks including hypertension require that such pregnancies be handled by a multidisciplinary team approach. PMID- 1412723 TI - The long-term effects of prophylactic OKT3 monoclonal antibody in cadaver kidney transplantation--a single-center, prospective, randomized study. AB - We conducted a randomized, prospective study to determine the long-term effects of prophylactic OKT3 in cadaveric renal transplantation. In the first group of patients (n = 56) OKT3 (5 mg/day) was administered for the first 14 postoperative days in association with azathioprine (AZA) and low-dose steroids, cyclosporine (CsA) being introduced on day 11. The other group of patients (n = 52) received CsA from the first POD, together with AZA and steroids. Both protocols were identical from POD 14 on. The total number of infections was higher in OKT3 patients (124/1455 patient-months [P-M] vs. 68/1320 in CsA patients, P less than 0.001) without impact on patient survival (94.5% in OKT3 vs. 93% in CsA patients). OKT3 patients experienced a lower number of rejection episodes (61 per 1455 P-M of risk exposure vs. 81/1320 in CsA patients, P less than 0.05). In addition, the frequency of corticoresistant rejection episodes was lower in OKT3 patients (9 out of 61 vs. 24 out of 81 in CsA patients, P less than 0.05). This resulted in a trend toward improved overall graft survival (83% vs. 75%, P = 0.12) and in a significant increase in immunological graft survival (92% vs. 79%, P = 0.02) in OKT3 patients at 3 years. Taken together, these data suggest that prophylactic OKT3 therapy might have long-term beneficial effects in cadaveric renal transplantation. PMID- 1412724 TI - Plasma fibronectin levels during acute rejection and acute tubular necrosis in renal transplant patients. AB - Fibronectin (Fn), an acute phase glycoprotein synthesized by the liver, has an important immunomodulatory role. We have investigated the changes in plasma Fn in patients after renal transplantation in order to determine whether these changes predict graft injury or rejection episodes. Besides normal healthy controls, healthy pregnant controls, and a trauma control group, we used two groups of chronic renal failure patients as controls: group I, patients with end-stage renal failure (ESRF) on peritoneal dialysis; group II, patients with ESRF on hemodialysis. These were compared with two groups of renal transplant patients: group III, patients 3 months after successful renal transplantation; group IV, patients studied sequentially 10 days immediately posttransplantation. The renal transplant patients were treated with low-dose cyclosporine, azathioprine, and steroids. Citrated plasma samples were collected for Fn assay by a sandwich-type ELISA and for SDS-PAGE analysis and Western blotting. The mean plasma Fn levels were as follows: healthy controls 311.6 SEM, 13.5 micrograms/ml; healthy pregnant controls 357 SEM, 5.9 micrograms/ml; trauma controls 262.3 SEM 31.7, micrograms/ml; group I 169 SEM, 25.1 micrograms/ml; group II 199 SEM, 27.2 micrograms/ml; group III 272 SEM, 21.7 micrograms/ml; group IV 212 SEM, 27.4 micrograms/ml (day 3 postop). There was a significant difference in the plasma Fn levels on day 3 posttransplant between the patients with delayed and immediate renal function (P less than 0.03) (group IV). A significant decrease in plasma Fn levels occurred immediately after steroid therapy was stopped (P less than 0.03) in patients treated for acute rejection. Plasma Fn levels were significantly decreased in the presence of delayed graft function but did not predict rejection. PMID- 1412725 TI - The influence of increased age and age matching on graft survival after first cadaveric renal transplantation. AB - We examined the influence of donor and recipient age as well as close donor and recipient age matching by analysis of the actuarial survival of 397 consecutive first cadaveric renal transplants carried out in the years 1987 to 1990. Graft failure was defined as return to dialysis, transplant nephrectomy, or death of the recipient from any cause. Overall 1-, 2-, and 3-year actuarial graft survival was 87, 84, and 79%. No effect on graft survival in adult patients was seen of advanced age of either donor or recipient. The source of the donor whether from within or outside the North Western Regional Health Authority did not influence outcome whatever the donor age. Results from patients in whom the donor was within 5 years of the recipient's age were no different from those obtained when the age difference was greater than 5 years. These data do not support the hypothesis that close age matching influences graft survival. Age matching need not be used as a recipient selection criterion. As neither recipient nor donor age influenced early graft survival, consideration should be given to increasing the average age of both donors and recipients. PMID- 1412726 TI - Quality-of-life changes and psychiatric and neurocognitive outcome after heart and liver transplantation. AB - A prospective study compared psychiatric, neurocognitive, and quality-of-life changes of heart and liver transplant patients. The 51 heart and 61 liver transplant candidates and recipients completed the Beck depression inventory (BDI), state-trait anxiety inventory (STAI), sickness impact profile (SIP), mini mental state (MMS), California verbal learning test (CVLT), Wisconsin card sorting test (WCST), trailmaking test (TMT), and the impact message inventory (IMI). Data were gathered before transplant and at 3-month intervals for up to 1 year after transplant. Psychometric tests scores were correlated with electroencephalograms for the liver patients. Both groups showed significant improvements after transplant in neurocognitive functioning, depressive symptoms, and quality of life. PMID- 1412727 TI - The relationship of serum IL-6 levels to acute graft-versus-host disease and hepatorenal disease after human bone marrow transplantation. AB - The potential involvement of cytokines in acute graft-versus-host disease led us to analyze interleukin-6 in serial serum sets from 22 allogeneic marrow recipients who developed either grade 3 or 4 GVHD (n = 10), grade 2 GVHD (n = 6), or grade 1 or no diagnosed GVHD (n = 6). A total of 279 serial serum samples taken three times weekly before day 35 were analyzed. Maximum IL-6 levels were greater than 40 U/ml (range, 40-1536 U/ml), 11-40 U/ml, and less than or equal to 10 U/ml for six, eleven, and five patients, respectively. Serum IL-6 peaks were temporally related to onset of GVHD, onset of a syndrome of hepatorenal dysfunction (HRD), or bilateral lung infiltration. Eight of ten patients who developed grade 3 or 4 GVHD overall had IL-6 maxima of greater than 10 U/ml an average of 1.5 +/- 1.8 days before the clinical onset. Fifteen of 17 patients with peak IL-6 levels greater than 10 U/ml developed symptoms of hepatic and renal dysfunction within three days of the peak, while none of five patients with less than or equal to 10 U/ml of Il-6 developed HRD. Regression analysis demonstrated a linkage between the log magnitudes of the serum IL-6 peaks and onset of either GVHD or HRD within three days (P = 0.001). Furthermore, IL-6 peaks tended to precede GVHD onset for the 10 patients whose GVHD onset and IL-6 peak were within three days of each other (P = 0.02). These results, confirmed by both specific bioassay and by IL-6 ELISA, support the idea that acute GVHD in humans involves a cytokine cascade that includes production of IL-6 in addition to the previously reported involvement of tumor necrosis factor alpha and interferon-gamma. PMID- 1412728 TI - Pretransplant and posttransplant antibodies in human corneal transplantation. AB - The purpose of this study was to measure the association between antibody formation and endothelial corneal allograft reactions in 533 consecutive corneal graft recipients. The median follow-up time of these recipients was 732 days. Pretransplant panel-reactive antibodies were not found to be associated with endothelial corneal allograft reactions. Out of 533 recipients, 239 developed posttransplant antibodies during the course of this study. The formation of posttransplant antibodies was frequent in recipients with pretransplant antibodies and in HLA-A,-B-incompatible recipients. Posttransplant antibodies most often appeared within the first six months after transplantation whereas endothelial allograft reactions most often occurred later. Out of 65 recipients who developed PPRA and underwent an allograft reaction, 53 had a PPRA peak prior to, or at about the time of, the allograft reaction. Corneal allograft reaction events diagnosed during the second and third year after surgery were correlated with PPRA formation during the first year after grafting. The 36-month reaction free survival rate of transplants was estimated at 72% in recipients with PPRA compared with 86% in recipients without PPRA (log rank P value = 0.002). Furthermore, posttransplant antibody formation altered the outcome of corneal allografts in both HLA-A and -B-compatible and -incompatible recipients. These findings suggest that posttransplant antibody development represents a high risk of endothelial corneal allograft reactions. PMID- 1412729 TI - Induction of specific tolerance to class I-disparate renal allografts in miniature swine with cyclosporine. AB - Previous studies in miniature swine have suggested that the mechanism underlying the spontaneous development of tolerance in one third of one-haplotype class I disparate renal allografts (i.e., ag----ad) involves a relative T cell help deficit at the time of first exposure to antigen. If this hypothesis were correct, then one might expect the administration of an immunosuppressive agent capable of inhibiting lymphokine production during this period to lead to the induction of tolerance to class I MHC antigens in two-haplotype class I mismatched renal allografts (i.e., gg----dd), which are otherwise uniformly and acutely rejected. This hypothesis was tested in eight two-haplotype class I disparate, class II matched donor-recipient pairs, in which recipients were treated with cyclosporine 10 mg/kg, i.v. q.d. for 12 days. This protocol led to the induction of long-term (greater than 100 days) specific tolerance in 100% of recipients, as compared with control animals that rejected grafts in 13.7 +/- 0.9 days (P less than 0.0001). The specificity of tolerance was assessed both in vivo with subsequent skin grafts and in vitro by mixed lymphocyte response (MLR) and cell-mediated lymphocytotoxicity (CML). Survival of donor-specific skin grafts was prolonged compared with skin grafts bearing third-party class I antigens (19.5 +/- 2.0 versus 11.5 +/- 2.0 days, n = 4, P less than 0.05). Tolerant recipients had markedly diminished or absent anti-donor MLR and CML responses, but maintained normal reactivity to third party. Four of eight CsA-treated recipients showed detectable levels of anti-donor IgM, while none demonstrated the presence of anti-donor IgG, which was found in all rejecting controls. PMID- 1412730 TI - Thromboxane augmentation of alloreactive T cell function. AB - Thromboxane (Tx) plays a vital role in the dysfunction and ultimate rejection of MHC-disparate renal allografts. In addition to its potent vasoconstrictory properties, in vivo studies have implied that Tx is capable of promoting immune cytotoxic T cell function within transplants. In this study, we have examined the in vitro effect of Tx inhibition on alloreactive immune cells using MHC-disparate mouse strain combinations. Coculture of either Tx-synthetase or Tx-receptor inhibitors modified the response of unprimed mouse lymphoid populations in a primary MLR, implying that Tx inhibition and not endoperoxide shunting was responsible for the modulatory effects seen. For example, B10.S lymphoid cells displayed decreased proliferation to H-2 disparate B10.A cells with Tx inhibitors present during the MLR, at pharmacologically active drug concentrations. Moreover, in vitro addition of TxA2 had an augmentory effect on the response in the primary and secondary MLR. Interleukin 2 production and percentages of T cell populations in the primary MLR were not affected by the presence of these compounds, although CD4 and CD8 expression was often increased in the treated populations. Finally, alloreactive primed effector cells also displayed reduced proliferation to specific alloantigen in a secondary MLR when Tx inhibitors were also present, although responses to IL-2 by T cells were not influenced by thromboxane inhibition. These data imply that thromboxane is an important immunoregulatory mediator capable of potentiating the function of naive and primed alloreactive immune T cell populations crucial to the rejection of the transplant. PMID- 1412731 TI - Reduction of delayed-type hypersensitivity by the injection of n-3 polyunsaturated fatty acids in mice. AB - The effects of injection of n-3 polyunsaturated fatty acids (PUFAs) on the delayed-type hypersensitivity (DTH) response was investigated in mice. Mice were immunized with sheep red blood cells (SRBCs). Six days later 50 microliters of a 20% SRBC suspension was injected into the right hind footpad of each mouse. Just before the challenge of SRBCs, various amount of a trieicosapentaenoyl-glycerol emulsion (10%) was injected through tail veins (5 mice per each dose). Then 24 hr later the dorsoventral thickness of the right hind footpad was measured and compared with that of the left hind footpad. The difference in thickness between both footpads was regarded as the DTH response. The effect of the emulsion on DTH was dose-dependent; the DTH responses (in mm) in the control group (injected with 0.5 ml of a 2.5% glycerol solution through tail veins) and EPA-injected groups (with 5 mg, 10 mg, and 20 mg) were 1.53 +/- 0.16 (mean +/- SEM), 1.09 +/- 0.14, 0.43 +/- 0.07 (P less than 0.005), and 0.36 +/- 0.13 (P less than 0.005), respectively. The DTH response was also depressed by the injection of a tridocosahexaenoyl-glycerol emulsion. Consequently, n-3 PUFA emulsions have clinical implication in DTH-related diseases such as rejection of allografts. PMID- 1412733 TI - Resistance and susceptibility of neural cells to lysis by cytotoxic lymphocytes and by cytolytic granules. AB - The susceptibility of neural cells to immune-mediated lysis by alloantigen specific cytotoxic lymphocytes is important in understanding cell-mediated immune responses during rejection of transplanted neural tissues and in inflammatory responses of the central (CNS) and peripheral (PNS) nervous systems. In this study, we used 51Cr-release and granzyme A assays to examine whether primary cultures of astrocytes and CNS and PNS neurons could serve as targets for alloantigen-specific CTLs and granule-mediated lysis. The level of astrocyte killing by alloantigen-specific CTLs correlated with expression of the class I gene products of the major histocompatibility complex. Astrocytes cultured for 1 2 weeks did not express class I MHC antigens and were not susceptible to lysis by activated alloantigen-specific CTLs. Lengthening the astrocyte culture period to 3 weeks resulted in class I MHC antigen expression on the astrocyte surface and alloantigen-specific lysis. Astrocytes of all ages tested were susceptible to lysis by isolated cytolytic lymphocyte granules. PNS neurons of various ages tested also served as targets for CTLs and were lysed by isolated granules. In contrast, CNS neurons did not express class I MHC antigens and were highly resistant to killing by CTLs and lymphocyte granules. CNS neurons and astrocytes did not trigger specific granzyme A secretion from effector cells. In the presence of leucoagglutinin, CTLs-specific recognition of target cells is bypassed, and virtually any cell, regardless of its antigens, is killed nonspecifically. Although leucoagglutinin-treated CNS neurons and astrocytes triggered increased granzyme A secretion from effector cells, only astrocytes were lysed in an antigen-nonspecific manner, whereas CNS neurons remained strikingly resistant. These results suggest differences in the susceptibility of PNS and CNS neurons to T cell-mediated lysis. CNS neurons appear to possess protective mechanisms that render them refractory to CTL-mediated lysis and granule-mediated lysis, whereas PNS neurons and astrocytes are far more susceptible to both types of immune attack. PMID- 1412734 TI - The time course of cell-mediated lympholysis in rat hepatic allograft recipients pretreated with a single donor-specific blood transfusion. AB - A single intravenous injection of 1 ml freshly heparinized donor blood seven days before transplantation significantly prolonged the survival of subsequent donor specific hepatic allografts in the fully allogeneic ACI(RT1a-to-LEW(RT1l)) rat combination. The time course of cell-mediated lympholysis was studied in this animal model. The activity of CML in lymphocytes infiltrating into the hepatic allograft (CML-G) and in the spleen (CML-S) was determined by measuring % lysis of donor Con A blast cervical lymph node cells. Preoperative DST resulted in an increased activity of CML-S with a peak (31.6%, E/T = 150) on day 7. This increased CML-S activity after DST rapidly declined during the first days following hepatic transplantation. The activities of both CML-S and CML-G then increased after transplantation and reached peaks on days 15 (48%, E/T = 150) and 20 (2.57%, E/T = 75), respectively. These were much higher than the peak values of CML-S (11.2%, E/T = 150) on day 7 and CML-G (19.5%, E/T = 75) on day 6 in untreated controls and were followed by a subsequent gradual decrease in those activities to preoperative levels by day 113 posttransplant. Phenotypic analysis of lymphocytes infiltrating grafts in DST-treated hosts demonstrated that the CD4/CD8 ratio remained relatively constant (less than 1.0). While the ratio in control grafts increased and reached a peak (2.17) on day 9. Histological examination revealed that mononuclear cell infiltration of grafts reached a peak on day 9 in both DST-treated hosts and controls. This mononuclear cell accumulation gradually subsided in DST-enhanced grafts. The mitotic index of graft hepatocytes reached a peak on day 15 in DST-treated hosts and on day 7 in control. The evidence of prolonged survival of hepatic grafts in recipients pretreated with DST, despite the presence of cytotoxic T cells with increased CML activity in vitro, suggests that effector cytotoxic cell activity may not be necessary for rat liver allograft rejection and that there may be limitations in measuring host cytotoxic activity simply by CML assays. PMID- 1412732 TI - Maturing thymocytes in accelerated rejection of cardiac allografts in presensitized rats. AB - LBNF1 cardiac allografts are rejected within 36 hr in LEW rats sensitized with BN skin grafts 7 days earlier (acute rejection in unmodified hosts = 8 days). We have studied and compared the function and migration patterns of thymocytes one day after engraftment in sensitized recipients, unmodified hosts, and normal naive rats. Thymocytes from animals experiencing accelerated rejection were more mature and functionally active, as shown by a significant elevation in percentage of OX-44+ (CD37+) cells, increased alloreactivity to BN and WF antigens, and proliferative responses to Con A and exogenous IL-2. However, the cells could neither lyse BN targets in vitro nor trigger rejection of otherwise indefinitely functioning test cardiac allografts in immunologically unresponsive T cell deficient (B) rats after adoptive transfer. The traffic of 111In-labeled thymocytes was then evaluated. The migration index increased significantly during accelerated graft rejection, with thymocytes preferentially circulating in the blood, penetrating peripheral lymph nodes--and, interestingly, migrating back to the thymus. Thus, immunoresponsive and functionally active thymocytes, which lack the ability to recognize primed specific antigen, appear during accelerated rejection of cardiac allografts in sensitized rats. These cells migrate to the periphery, and then return in large numbers to their site of origin, the thymus. Hence, this study describes a novel behavior of thymocytes in the state of host alloreactivity that is distinct from the physiological one in otherwise normal thymus. PMID- 1412735 TI - Immunogenicity of MHC class I alloantigens expressed on parenchymal cells in the human kidney. AB - The goal of the present study was to examine the capacity of human kidney cell lines (KCL) to elicit T cell responses to MHC class I alloantigens. KCL exhibited the phenotypic characteristics of tubular epithelial cells and were devoid of detectable contamination with leukocytes. Coculture of normal peripheral blood leukocytes (PBL) with allogeneic KCL elicited cytolytic T lymphocytes (CTL) that lysed the stimulating KCL but failed to lyse third-party KCL. Cell panel and antibody blocking studies demonstrated that the CTL were directed to the HLA class I alloantigens expressed on the KCL stimulators. Purified T cells completely failed to mount a CTL response to KCL, but the response could be reconstituted by supplementing the cultures with either autologous non-T cells or supernatant from a mixed lymphocyte culture (MLC). IL-2, but not IL-1, IL-4, IL 6, or gamma-interferon, restored the anti-KCL response, suggesting that IL-2 is the active factor in the MLC supernatant. Induction of class II antigens on the KCL stimulators with gamma-IFN failed to restore a CTL response, suggesting that KCL are deficient in a costimulatory factor important for class II restricted T helper responses. Nonetheless, our data demonstrate that parenchymal cells in the kidney are capable of presenting class I antigens to alloreactive T cells and, therefore, may contribute to the immunogenicity of renal allografts. PMID- 1412736 TI - Marginal benefit of donor corticosteroid therapy in prolonged lung allograft preservation. PMID- 1412737 TI - Herpes simplex virus and neutropenia following bone marrow transplantation. PMID- 1412738 TI - Extended survival of MHC-identical allogeneic islet grafts in diabetic BB rats- the effect of an interleukin 2 receptor-targeted immunotherapy. PMID- 1412739 TI - The transplantation of encapsulated islets of Langerhans into the peritoneal cavity of the biobreeding rat. PMID- 1412740 TI - A comparison of initial flushing solutions in liver preservation. PMID- 1412741 TI - Oxygenation of the human pancreas during preservation by a two-layer (University of Wisconsin solution/perfluorochemical) cold-storage method. PMID- 1412742 TI - Maintenance of liver adenine nucleotides during cold ischemia. The value of a high-pH, high-pK flush. PMID- 1412743 TI - Evidence that the risks of misoprostol outweigh its benefits in stable cyclosporine-treated renal allograft recipients. PMID- 1412744 TI - The impact of HLA matching on graft survival. PMID- 1412745 TI - The low number of natural killer cells in renal transplant recipients with de novo malignancies. PMID- 1412747 TI - The role of natural IgM in the hyperacute rejection of discordant heart xenografts. AB - The mechanism of xenograft hyperacute rejection in discordant species combinations remains controversial. The purpose of this work was to study the role of natural antibodies in the hyperacute rejection of guinea pig hearts transplanted into rats, a highly discordant combination. This study was conducted in vitro, ex vivo, and in vivo. The endothelial cells of the graft being the first targets damaged in the process of hyperacute rejection, the binding of rat natural antibodies to guinea pig endothelial cells was studied by immunofluorescence. The study was carried out in vitro on guinea pig endothelial cells in culture, and ex vivo on isolated guinea pig hearts perfused with either rat serum or immunoglobulins or immunoglobulin fragments bearing the antigen binding site. In vitro and ex vivo, rat natural IgM were found to bind specifically to guinea pig endothelial cells, since IgM fragments bearing the antigen-binding site (Fab mu and Fab' mu) could be detected on these cells. IgM fragments were able to inhibit the fixation of native IgM molecules. In contrast, rat IgG only bound to endothelial cells through Fc portions. Thus rat natural IgM might play a role in hyperacute rejection by binding to the graft endothelial cells and triggering the complement cascade activation. In order to test the role of natural IgM in vivo, isolated guinea pig hearts were first perfused with rat Fab' mu, which inhibit the binding of IgM and are unable to activate the complement cascade. These hearts were then transplanted into Lewis rats. The rejection time of Fab' mu-perfused guinea pig hearts was prolonged compared with hearts perfused with buffer or IgG F(ab')2. Therefore, in the guinea pig to rat combination, preventing the binding of the recipient's natural IgM to the graft endothelium delays the hyperacute rejection. In addition, natural IgM are likely to play a greater role than natural IgG. PMID- 1412746 TI - Discordant xenograft rejection in an antibody-free model. AB - Newborn pigs prevented from suckling colostrum were shown to have less than 0.05 micrograms/ml total immunoglobulin present in their serum. Rabbit heart xenografts transplanted heterotopically into the neck of such pigs were hyperacutely rejected, with a mean survival time of 92 +/- 14 min (mean +/- SD). Pigs which had been allowed to suckle and whose serum contained 10-15 mg/ml maternal immunoglobulin hyperacutely rejected rabbit heart xenografts in 109 +/- 62 min. Histological studies showed no Ig binding but complement component 3 (C3) binding to rabbit hearts placed in immunoglobulin-negative pigs. Prolongation of rabbit heart xenograft survival was achieved by administering cobra venom factor (1 mg/kg) to the pigs pretransplant. These data show hyperacute xenograft rejection in the absence of antibody and suggest that its cause is activation of complement by the alternative pathway. PMID- 1412748 TI - Histological and immunopathological analysis of recovered encapsulated allogeneic islets from transplanted diabetic BB/W rats. AB - Allogeneic islets encapsulated in an alginate/poly-L-lysine membrane and transplanted into diabetic BB/W rats resulted in graft failure within 2 weeks of transplantation. Graft failure was associated with a dense pericapsular infiltrate (PCI) that resulted in necrosis of the encapsulated islets. The PCI could be inhibited by immunosuppressive agents, including cyclosporine and dexamethasone, and this resulted in a significant increase in graft survival. Immunopathological characterization of the PCI indicated that there was a predominance of macrophages. T helper cells also appeared to be present in this PCI. Empty capsules were also found to induce a similar PCI that was identical in composition to that found around encapsulated islets. Thus alginate/poly-L-lysine capsules do not appear to be biocompatible and may account for the variable results in islet graft survival found with these capsules. PMID- 1412749 TI - The effects of 16, 16 dimethyl prostaglandin E2 therapy alone and in combination with low-dose cyclosporine on rat small intestinal transplantation. AB - The use of prostaglandin E (PGE) in the setting of allotransplantation both clinically and experimentally has been suggested because PGE has significant immunosuppressive effects and potentially could lessen the toxic effects of cyclosporine. In the present study, we examined the immunosuppressive effects of 16,16 dimethyl prostaglandin E2 (dmPGE2) alone and in combination therapy with low-dose CsA to assess the clinical course, histology and expression of monocyte/macrophage procoagulant activity (PCA) following small intestinal transplantation in a heterotopic model of rat allograft rejection. Therapy with low-dose CsA (1 mg/kg) failed to prevent rejection and all animals reached a terminal state by day 26. In contrast, animals treated with high-dose CsA (10 mg/kg) showed no clinical or histological evidence of rejection and all animals survived. The dmPGE2 (100 micrograms/kg/twice daily) delayed the onset of rejection, but all animals developed severe rejection and subsequently died. Treatment of animals with low-dose CsA (1 mg/kg) in combination with dmPGE2 (100 micrograms/kg twice daily) resulted in a delay in the onset (P = 0.05) and a reduction in the intensity of allograft rejection (P = 0.0001) compared with either agent used alone. Monocyte/macrophage procoagulant activity levels correlated with the degree of rejection in all animals (P = 0.03). There was a statistically significant relationship between PCA levels and the time of onset of rejection and histologic grade of rejection in all groups. The data presented here, therefore, demonstrate a beneficial role for long-term combination therapy with CsA and PGE in small intestinal transplantation and strongly suggest a role for allogeneic induction of PCA in the pathogenesis of rejection. PMID- 1412750 TI - Twenty-four-hour hypothermic preservation of rat liver with Euro-Collins and UW solutions. A comparative evaluation by 31P NMR spectroscopy, biochemical assays, and light microscopy. AB - A comparative study of 24 hr preservation at 4 degrees C of excised rat livers with Euro-Collins and hydroxyethyl starch-free University of Wisconsin (UWm) solutions has been conducted based on the assessment of (1) the cellular energy status determined by 31P NMR spectroscopy and (2) cellular injury estimated from the loss of purine compounds (inosine, hypoxanthine, xanthine, and uric acid) during cold ischemia and reperfusion measured by HPLC, the leakage of intracellular enzymes, and the modifications of parenchyma established by light microscopy. Recovery of nucleosides di- and triphosphate was greater in the UWm group (80 +/- 6% vs. 58 +/- 6%) while inorganic phosphate formation was comparatively reduced. During hypothermic storage, the UWm groups generated a higher amount of inosine and hypoxanthine (in relation to the presence of adenosine in the protective solution) while no xanthine or uric acid was detected due to the inhibitory effect of allopurinol. Conversely, large quantities of xanthine and uric acid were found in the reperfusate of the EC group, pinpointing the cytotoxic role of oxygen-derived free radicals in the generation of cellular damage, as also illustrated by a higher aspartate aminotransferase leakage in the EC group (devoid of allopurinol and glutathione. Light microscopy indicated no histological alterations in the UWm group and mild alterations in the EC group that showed ballooning of hepatocytes (no lactobionate and raffinose in EC) and an alternation of clarifications and eosinophilic condensations. This study clearly confirms and illustrates the overall superiority of UWm solution in liver transplant preservation. PMID- 1412751 TI - 31P NMR assessment of orthotopic rat liver transplant viability. The effect of warm ischemia. AB - The relationship between NMR visible high energy phosphates and transplant outcome for the case of liver damage by warm ischemia was investigated. In vivo 31P nuclear magnetic resonance (NMR) spectroscopy of rat liver was performed before the induction of warm ischemia in the donor and 20 min after reestablishment of portal blood flow in the recipient. Pretransplant damage was varied by subjecting the livers to 0, 15, 30, or 60 min of warm ischemia prior to harvesting. In the controls (0 min warm ischemia), 4 of 4 rats survived transplantation (one week survival end-point) and the mean NTP recovery was 94 +/ 8%; 3 of 6 rats survived in the 15 min warm ischemia group. Mean NTP recovery was 77 +/- 20% in the 15 min survival subgroup and 32 +/- 20% in the nonsurvival subgroup. Of 6 rats, 1 survived in the 30 min group. NTP recovery was 44% for the 30 min survivor and 37 +/- 5% in the nonsurvival subgroup. Of 4 rats, 1 survived in the 60 min warm ischemia group. NTP recovery was 56% for the 60 min survivor and 28 +/- 7% in the nonsurvival subgroup. Overall, there was a significant difference between the mean NTP recovery of the survival and nonsurvival subgroups (78 +/- 21% versus 31 +/- 18%, P < 0.001). The dividing line between the survival and nonsurvival groups was approximately 50% NTP recovery. Of 9 rats with liver NTP recovery greater than 50%, 8 survived while 10 of 11 rats with less than 50% recovery died. NMR visible NTP recovery 20 min after the reestablishment of portal blood flow was a good indicator of transplant outcome in the case of rat liver damage by warm ischemia. PMID- 1412752 TI - A comparison of histidine-lactobionate and UW solution in 48-hour dog liver preservation. AB - Many modifications of the UW solution have been reported to yield successful results in rat liver preservation and transplantation. One solution used histidine, in combination with lactobionate (HL-I), and gave superior preservation of the rat liver when compared with the UW solution. In this study we have compared the HL-I solution with 90 mM histidine, HL-II solution with 30 mM histidine, and the UW solution in dog liver preservation and transplantation. Dog livers were preserved for 48 hr in one of the three solutions and transplanted. The peak AST and ALT values were highest in livers preserved in HL I, intermediate in UW solution, and lowest in HL-II. However, there were no significant differences among survival rates (average 5-7 days per group), posttransplant serum concentration of liver enzymes (AST, ALT, LDH, and alk phos), clotting factors (PT and PTT), bilirubin, and fibrinogen concentration for each group. Dogs were sacrificed or died within 5-7 days due to rejection in nonimmunosuppressed dogs. Also, rat livers were preserved in the HL-II solution or in a solution in which histidine was replaced by isoleucine (IL-I). Isoleucine is an amino acid with a molecular mass similar to that of histidine, but is not as good a hydrogen ion buffer as histidine at the pH used for liver preservation (7.4). The buffer capacity of the IL-I solution was similar to the UW solution, but about one-half as much as the HL-II solution. Rats receiving a liver preserved for 30 hr in HL-II or IL-I were 100% viable. Rats receiving a liver preserved for 40-44 hr in HL-II or IL-I showed less survival (33% and 25%, respectively). This shows that histidine can be effectively replaced by isoleucine in a preservation solution and gives equivalent preservation results. Thus, the mechanism of improvement of liver preservation with histidine is not due to its action as a hydrogen ion buffer. These studies show that, although the HL solutions are superior for preservation of the rat liver, they are not superior to the UW solution for preservation of the dog liver. However, as others have shown in the rat liver transplant model, a simplified UW solution (HL-II) appears effective in dog liver preservation. The dog liver transplant model remains a more appropriate model for testing new preservation solutions prior to initiation of clinical trials. PMID- 1412753 TI - The spectrum of Pneumocystis carinii infection after liver transplantation in children. AB - We report the experience with Pneumocystis carinii lung infections in the 109 children undergoing liver transplantation at our hospital between August, 1985 and May, 1989. PCP developed in 9 of the 86 patients (10%) surviving > or = 6 weeks after transplantation and not receiving P carinii chemoprophylaxis. Of the 59 patients undergoing BAL 2 or more weeks after transplantation there were 16 specimens from 14 patients (24%) positive for P carinii. These patients had a spectrum of illness ranging from asymptomatic to severe pneumonia requiring mechanical ventilation. The mean interval from first transplantation to bronchoalveolar lavage positive for P carinii was 24.9 weeks and the mean interval to first PCP was 28.0 weeks. The earliest and latest occurrences of PCP were 7 weeks and 73 weeks, respectively, after transplantation. There were no complications attributed to BAL. PMID- 1412755 TI - Tissue factor in normal and transplanted human kidneys. AB - Tissue factor (TF) plays a central role in the initiation of blood coagulation that frequently is enhanced in renal allografts. The identification and localization of TF was studied immunocytochemically in biopsies from normal and transplanted human kidneys and classified according to its distribution. The clinical status of each allograft was then correlated with the TF classifications. From these correlations, four distributional types of TF were identified. In normal kidneys, TF was localized to glomerular epithelium and basement membranes. Glomerular TF expression did not colocalize with mesangial or endothelial HLA-DR reactivity as determined by double antibody techniques. Tissue factor in donor kidneys also was identified in the renal capsule and in the adventitia of large arteries. These structures were not reactive in long-term transplanted grafts. Some cadaver kidneys prepared for transplantation had depleted glomerular TF, and exhibited TF reactivity within stromal tissues. Long term allografts with progressive loss of renal function and kidneys with advanced rejection exhibited diminished TF reactivity of glomerular epithelium and basement membranes. This was frequently associated with fibrin deposition within the glomeruli and in the intertubular microcirculation. These findings indicate that the evaluation of TF in transplanted kidneys is related to the prognosis of graft survival. PMID- 1412754 TI - A randomized trial of cyclosporine and prednisolone versus cyclosporine, azathioprine, and prednisolone in primary cadaveric renal transplantation. AB - A randomized trial was performed with the aim to compare two immunosuppressive treatment schedules in adult recipients of first cadaveric renal transplants. A total of 229 patients were randomized to double therapy with cyclosporine and prednisolone and 234 patients were randomized to triple therapy with cyclosporine, azathioprine, and prednisolone. Minimum follow-up was 4 years. The actuarial 5-year patient survival was 79.8% in the double therapy group and 82.3% in the triple therapy group (n.s.). The corresponding graft survival figures were 54.4% and 59.6% in the two groups, respectively (n.s.). There were no differences between the groups regarding cause of death or cause of graft loss. Renal function as determined by serum creatinine did not differ between the groups and was stable throughout the observation period. Azathioprine was instituted in a total of 51 patients randomized to double therapy. This subgroup of patients had a patient and graft survival not different from the remaining patients randomized to double therapy or from the patients randomized to triple therapy. There were no differences between the double and triple therapy groups regarding incidence and timing of acute rejection or infections. The incidence of other medical diseases and adverse events such as nephrotoxicity or malignancy did not differ between the groups. Azathioprine-induced leukopenia was uncommon (19 episodes in the triple therapy group). In a multivariate analysis of the whole series the only covariates that significantly influenced graft survival were age of recipient and occurrence of acute rejection, while among other factors treatment schedule did not. Thus this prospective study, in accordance with previous such studies, failed to find support for the use of triple therapy as first choice immunosuppression in first cadaveric renal transplantation. However, the study could not rule out the possibility that some patients at risk for the development of irreversible rejection or nephrotoxicity of CsA might benefit from the addition of azathioprine to the treatment schedule. PMID- 1412756 TI - Outcome of cardiac transplant recipients with a positive donor-specific crossmatch--preliminary results with plasmapheresis. AB - To assess the influence of a positive T or B cell IgG crossmatch on the development of rejection and mortality following cardiac transplantation, we reviewed all cardiac transplants performed in Utah between March 1985 and October 1990. Of the 328 cardiac allograft recipients, 11 (3.4%) had an IgG positive crossmatch. Actuarial survival at 24 months in the positive crossmatch group was 57.3% +/- 0.02 while that of the controls was 86.1% +/- 2.1 (P < 0.05). Allograft rejection occurred earlier in recipients with a positive crossmatch (10.0 +/- 5.8 days versus 34.0 +/- 2.3 days, P < 0.001). The first allograft rejection episode in patients with a positive crossmatch was characterized by immunoglobulin and complement deposition in small blood vessels and interstitial edema and endothelial cell activation in the absence of a lymphocytic infiltrate. Furthermore, the allograft rejection in the positive crossmatch group was accompanied by hemodynamic compromise in a large proportion of the patients (73%). In addition to augmentation of immunosuppression, plasma exchange therapy was performed within the first week following transplantation in 8 of the 11 positive crossmatch patients. Survival in the patients treated with plasma exchange (75%) appears to be better than in those not receiving plasma exchange (33%) within one week of transplantation. While immunosuppressive therapy aimed at the humoral arm of the immune system and plasma exchange therapy may improve survival in recipients with a positive donor-specific crossmatch, survival is worse in patients with a positive crossmatch than in patients with a negative crossmatch. Thus, it would appear prudent to prospectively crossmatch cardiac transplant candidates with a greater risk of developing a positive crossmatch, such as those potential recipients with an elevated level of panel-reactive antibodies. PMID- 1412758 TI - The effect of injection of donor bone marrow on the frequency of donor-reactive CTL in antilymphocyte serum-treated, grafted mice. AB - The survival of C3H/He skin grafts can be prolonged on B6AF1 mice immunosuppressed with ALS by the injection of C3H/He marrow 1 week postgrafting. The precursor frequencies of donor-reactive CTL in the spleen and lymph nodes of ALS-treated, grafted mice given donor marrow were compared with CTL frequencies observed in ALS-treated, grafted controls. Spleens and nodes were removed from experimental and control mice on days +8, +14, +21, +58, and 1 year postgrafting, and used as effectors in the LDA. Donor-reactive CTL in the marrow-injected group remained suppressed as long as the recipients maintained their grafts. The frequency of CTL to third-party antigens was normal in mice bearing long-term C3H/He grafts. When marrow-injected mice rejected their grafts, the total donor reactive CTL frequency returned to normal. In contrast, in ALS-treated controls that did not receive marrow, the total number of donor-reactive CTL returned to normal levels with recovery from the immunosuppressive effects of ALS. These results suggest that donor marrow suppresses the regeneration of donor-reactive CTL in the lymphoid tissues of ALS-treated mice, possibly by veto cell activity. PMID- 1412757 TI - The quality of life in renal transplantation--a prospective study. AB - Methodologically sound measures of quality of life are required to judge accurately the impact of successful renal transplantation on patient well-being. The time trade-off (TTO) method is a reproducible and valid measure which we used to prospectively assess changes in the quality of life of 27 patients on maintenance dialysis who subsequently underwent renal transplantation. TTO scores approaching 0 signify a very poor quality of life, while scores approaching 1 represent perfect health. Of 98 dialysis patients who completed baseline TTO interviews, 31 consecutive patients subsequently received 28 cadaveric and 3 living related kidney transplants. Four of 31 patients did not complete a second TTO assessment, because of death in 2 patients and graft loss in 2 others. The remaining 27 patients completed a second TTO interview an average of 30.9 months following transplantation (range 1.5-52, 95% confidence interval [CI] 24.4-37.5) and formed the study cohort. At the time of study the mean serum creatinine for the cohort was 173 mumol/L (range 90-290, 95% CI 152-195 mumol/L). The employment rate rose 27% following transplantation (P = 0.10); but when males alone were analyzed, a significant increase of 38% (P = 0.048) was noted. During the dialysis period, the mean baseline TTO score was 0.41 (95% CI 0.33-0.49), confirming the observations of others. Following transplantation, the mean TTO score rose to 0.74 (95% CI 0.67-0.81), a difference that is statistically significant (P < 0.001). The mean increase in TTO score observed as a result of successful transplantation was 0.33 (95% CI 0.26-0.40). This magnitude of improvement was found in 20 of 27 patients (74%), whose TTO scores lay within or above the 95% CI (0.26-0.40) for the mean change in score of 0.33. One patient's score fell, while the remaining 6 patients had improvements in their TTO score which fell below the lower 95% CI value (0.26) for the mean change in score. We conclude that the 95% CI of 0.26-0.40 identifies a range in which clinically important improvements in quality of life will be found for the majority of patients receiving successful kidney transplants. PMID- 1412759 TI - Evidence that the antiproliferative effect of verapamil on afferent and efferent immune responses is independent of calcium channel inhibition. AB - Calcium channel blockers are capable of inhibiting the afferent and efferent limbs of the immune responses of human peripheral blood mononuclear cells in in vitro systems. This effect is thought to be related to the ability of the calcium channel blocker to limit the transmembrane flux of calcium. We report herein that two optical enantiomers of verapamil, one (S-) which is capable of blocking the slow calcium channel and mitogen-stimulated 45Ca++ uptake into human lymphocytes, while the other (R+) is incapable of either activity, share almost identical capabilities of depressing both the afferent and efferent limbs of immunity. These observations suggest that the inhibitory effects of verapamil on various afferent and efferent immune events are, in part at least, unrelated to the inhibition of transmembrane calcium flux. PMID- 1412760 TI - Prolongation of second heart transplants in rats. AB - Second clinical kidney grafts often survive longer than first grafts. Using a rat cardiac allograft model, we examined the conditions under which survival of a second graft can be longer than first graft survival. In the BUF-to-LEW combination, following rejection of the first transplant, second cardiac allografts from the same donor strain implanted immediately survived longer than the first grafts (P = 0.047). Although the mean survival time of first grafts was 9.0 days, second grafts implanted in the same animals survived 19.5 days. In contrast, when ACI donors were used for the same LEW recipients, the second grafts were rejected in 3 days compared with 6.6 days for first grafts. Donor specific spleen cell transfusions in these combinations resulted in prolonged survival in the BUF to LEW combination, but had no effect when the donor strain was ACI. Second grafts from BUF had prolonged survival following rejection of the first graft. Thus the histocompatibility difference was a determining factor of whether or not prolongation would be obtained. Another factor was timing of the second transplant. If 7 days were allowed to elapse following rejection of the first graft before implantation of the second, the enhancement effect was lost. Moreover, in the LEW-to-ACI combination in which second grafts were rejected rapidly, removal of the first graft after 7 days (before rejection), resulted in prolonged survival of the second graft. There is, therefore, a window of time before rejection of first grafts and shortly thereafter, when the enhancement effect can be obtained. Passive transfer of serum in the BUF-to-LEW combination resulted in enhancement, but transfer of splenic cells was ineffective. We conclude that graft rejection can result in induction of enhancement during a specific period, after which this effect is lost; and that enhancement can be obtained only in certain strain combinations. This suggests that human patients with heart transplants that reject might benefit from a second graft, even from a donor with a mismatch similar to the first graft. PMID- 1412761 TI - Orthotopic corneal transplantation in mice--evidence that the immunogenetic rules of rejection do not apply. AB - The fate of orthotopic corneal transplants has been studied in inbred strains of mice. Using a surgical technique that achieves > 95% success of syngeneic cornea grafts, it was determined that a high proportion of orthotopic cornea allografts were accepted indefinitely, irrespective of the degree of immunogenetic disparity between graft donor and recipient. Grafts that succumbed to irreversible rejection developed extensive corneal edema and intrastromal neovascularization as harbingers of corneal opacity and endothelial cell failure. The highest rate of rejection occurred among grafts that confronted their hosts with multiple minor histocompatibility antigens, with or without major histocompatibility antigens. Much lower rates of rejection (< 35%) were observed when the donors of the grafts differed from recipients at class I and/or class II major histocompatibility loci. Corneal grafts that confronted their hosts with class II MHC alloantigens alone experienced early, acute inflammation, and eventually developed stomal neovascularization, but only a small minority of these grafts were eventually destroyed. Allogeneic corneas that were transplanted orthotopically into eyes of presensitized mice were uniformly subjected to an acute rejection process that produced opacity within three weeks; however, in a minority of instances, the inflammation and opacity subside, and after eight weeks the grafts displayed a clear, nonvascularized appearance. The high rate of success of even grossly histoincompatible orthotopic corneal allografts in mice resembles the extraordinary success of unmatched allogeneic corneas transplanted into human eyes. The results are discussed in terms of the possible mechanisms that permit orthotopic corneal allografts to enjoy significantly better survival than orthotopic grafts of other types of solid tissues. PMID- 1412763 TI - Progressive albuminuria and glomerulosclerosis in a rat model of chronic renal allograft rejection. AB - A significant proportion of renal allografts fail within several months or years after transplantation, primarily because of chronic rejection. The etiology and pathophysiology of this condition remain unclear. We studied the renal function, morphology, and immunohistology, in parallel, among F344-to-Lewis allografts (n = 23) and isografts (n = 13) over the course of 24 weeks. Only an initial 10-day course of CsA (5 mg/kg/day) was given to both groups to prevent acute rejection. Hypertension did not develop, although awake systolic blood pressure was significantly higher in allografts at the end of the study. Significant differences in urine albumin excretion (UalbV) between isografts and allografts were evident as early as 4 weeks after engraftment but rose dramatically by 20 weeks (3.3 +/- 0.7 vs. 21.2 +/- 3.7 mg/day, respectively, P < .001). This pattern continued until the conclusion of the study (5.0 +/- 1.1 vs. 53.5 +/- 7.6 mg/day, P < .001). Serum creatinine values were only significantly elevated in allografts at 16 weeks, which temporally corresponded to the dramatic increase in UalbV. However, renal blood flow and glomerular filtration rate, measured by paraaminohippurate and inulin clearances, respectively, were significantly lower in allografted organs, at 24 weeks. The frequency of glomerulosclerosis lesions was significantly increased in allografted kidneys at 24 weeks and correlated with UalbV values. Glomerular localization of mononuclear leukocyte subsets were equivalent between allografts and isografts; however, the numbers of interstitial macrophages, CD8+, and pan-T-cells were all significantly greater in allografts at 24 weeks. The infiltration of significantly greater numbers of macrophages and lymphocytes into the tubulointerstitium of the allograft group suggests a mononuclear leukocyte effector cell mediation of the progressive glomerular abnormalities in this model of chronic renal allograft rejection in the rat. PMID- 1412762 TI - Evidence that rapamycin rescue therapy delays rejection of major (MHC) plus minor (non-MHC) histoincompatible heart allografts in rats. AB - The capacity of delayed onset of rapamycin (RAPA) therapy to block process of destruction was examined in rats undergoing heart allograft rejection. Untreated Wistar Furth (WFu; RT-1u) recipients reject Buffalo (BUF; RT-1b) heart allograft with a mean survival time (MST) of 6.5 +/- 0.5 days. A 14-day i.v.infusion of 0.8 mg/kg RAPA begun on the day of transplantation prolonged the survival to 74.1 +/- 20.2 days (P < 0.001), 0.2 mg/kg to 32.2 +/- 10.0 days (P < 0.001), and 0.08 mg/kg to 36.4 +/- 11.8 days (P < 0.001). When RAPA therapy (0.8 mg/kg) was begun 3 or 4 days after transplantation, the grafts survived 85.2 +/- 31.1 (P < 0.001), and 70.2 +/- 43.3 (P < 0.005) days, respectively. Therapy initiated on day 5 was much less effective; most transplants were rejected within 10 days; one graft survived 32 and two grafts 60 days (MST = 17.6 +/- 20.0, NS). A 0.2 mg/kg RAPA dose prolonged graft survival with initial use on days 3 (31.6 +/- 12.2 days; P < 0.001) or 4 (31.4 +/- 8.1 days; P < 0.001) but not on day 5. The 0.08 mg/kg RAPA prolonged hearts only when started on day 3 (47.2 +/- 2.7 days; P < 0.001) but not on days 4 or 5. WFu recipients treated with a subtherapeutic dose of cyclosporine (1 mg/kg; 9.1 +/- 1.5 days) displayed prolonged heart allograft function when treated subsequently with RAPA (0.8 or 0.08) beginning from days 4, 5, or 6 postgrafting. These in vivo results are supported by in vitro experiments. The frequency of BUF alloreactive elements among normal WFu LN cells (fTc) was 337 +/- 139/10(6) T cells in limiting dilution assay. Addition of RAPA (1 muMol) at the beginning of culture significantly reduced (P < 0.025) the fTc to 17 +/- 6.6/10(6), or alternatively on days 4 or 6 to 37.3 +/- 20.0/10(6) and 58.6 +/- 21.8/10(6), respectively. Thus, both in vivo and in vitro data demonstrate that delayed RAPA therapy may interrupt alloimmune reactions. PMID- 1412764 TI - The use of DiI-marked hepatocytes to demonstrate orthotopic, intrahepatic engraftment following hepatocellular transplantation. AB - A novel method is described for marking primary hepatocytes with the fluorescent dye DiI prior to hepatocellular transplantation and identifying these cells within the hepatic parenchyma of recipient animals by fluorescence microscopy and flow cytometry. Optimal conditions are described for marking cells with DiI in suspension or in monolayer cultures prior to transplantation. DiI is shown to be nontoxic to hepatocytes and not to be exchanged between adjacent cells in vitro. Histological analysis of transplanted tissues shows DiI staining of engrafted hepatocytes and phagocytotic cells (Kupffer cells). This analysis shows that hepatocytes engraft within the hepatic parenchyma and exhibit a histological appearance indistinguishable from normal by conventional hematoxylin and eosin staining. Many previous reports of hepatocellular transplantation have been limited by their inability to unequivocally identify transplanted cells within the liver. These data illustrate the importance of having specific markers for transplanted cells that engraft in an orthotopic location and assume a normal morphological appearance. PMID- 1412766 TI - Reversible cyclosporine arteriolopathy. PMID- 1412765 TI - A transplantation antigen, possibly of mitochondrial origin, that elicits rejection of parental strain skin grafts by F1 rats. PMID- 1412768 TI - Allograft renal vein thrombosis in a kidney with two veins. PMID- 1412767 TI - Triiodothyronine treatment in brain-dead multiorgan donors--a controlled study. PMID- 1412769 TI - Unsuspected portal vein thrombosis associated with temporizing sclerotherapy prior to orthotopic liver transplantation. PMID- 1412770 TI - Improved immediate graft function with nifedipine in cyclosporine-treated renal allograft recipients--a randomized prospective study. PMID- 1412771 TI - Intraoperative kinetics and regional distribution of interleukin-6 during human liver transplantation. PMID- 1412772 TI - The immunohistopathology of obliterative bronchiolitis following lung transplantation. PMID- 1412773 TI - A role for MHC antigens in donor-specific blood transfusion for the inhibition of liver allograft rejection in the rat. PMID- 1412774 TI - Prevention of liver allograft rejection in rats by a short course of therapy with Brequinar Sodium. PMID- 1412775 TI - The influence of the glycogen content of the donor liver on subsequent graft function and survival in rat liver transplantation. PMID- 1412776 TI - The immunosuppressive effect of polyethylene glycol in a flush solution for rat liver transplantation. PMID- 1412777 TI - Prolongation of the survival of murine cardiac allografts by the vitamin D3 analogue 1,25-dihydroxy-delta 16-cholecalciferol. PMID- 1412778 TI - Inhibition of the proliferation of human thymocytes in vitro by rapamycin. PMID- 1412779 TI - Compensation for organ donors. PMID- 1412780 TI - The first liver transplant in Saudi Arabia and the Arab world. PMID- 1412781 TI - Forty years of transplantation--merely a prologue. PMID- 1412782 TI - Immunology of transplantation. PMID- 1412783 TI - Disparate regulation of interleukin-6 secretion from blood monocytes and human kidney cells by interleukin-4. PMID- 1412784 TI - Suppression of in vitro lymphocyte reactivity to PHA by lysates from human placentae: lack of correlation with gravida number. PMID- 1412785 TI - An immunohistochemical study of lymphocytes occurring in heart allografts in rats. PMID- 1412786 TI - Identification and characterisation of two glycoproteins of molecular weights 60 and 180 kd from human multigravid placenta having strong in vitro immunosuppressive activity. PMID- 1412787 TI - Donor-type blood and immunoadjuvant-induced accelerated cardiac allograft rejection: a rat model. PMID- 1412788 TI - Comparative study of skin graft survival rates in BALB/c mice treated with either cyclosporine A, cyclosporine G, or 1/1 combination of both. PMID- 1412789 TI - Effect of cyclosporine A at therapeutic and toxic doses on the superluteinized ovaries in BALB/c mice. AB - Administration of cyclosporine (CyA) at therapeutic (10 to 50 mg/kg per day) and at toxic doses (100 mg/kg per day) to gonadotropin-treated immature BALB/c mice led to detection of this drug in the blood and in the ovary at levels that were dose- and time-dependent, the maximum level reached in the blood was 23.8 micrograms/mL, and in the ovary was 0.164 micrograms/mg ovarian weight. Although these were toxic levels, there was no adverse effect on the survival rate as it ranged from 90% to 100%, nor did it induce body weight reduction. In addition, it did not cause any significant structural alterations in the ovarian tissues. The histology of the graafian follicles and the corpora lutea were the same as in the control. On the other hand, the numbers of the corpora lutea were decreased in the ovaries of the CyA-treated mice. This was parallel to the reported decrease in plasma progesterone level to values less than that of the control. These results indicate that the use of gonadotropin primed mice decreased the degree of CyA-induced toxicity. PMID- 1412791 TI - Complement-mediated damage to liver xenografts in an isolated perfusion circuit- electron microscopic findings. PMID- 1412790 TI - Efficacy and mechanism of action of rapamycin in presensitized recipients of experimental allografts. PMID- 1412792 TI - Tissue typing--minimum requirements for clinical transplantation. PMID- 1412793 TI - The relevance of HLA A,B,C, matching on graft survival, patient survival, and graft function in living related renal transplant patients treated with cyclosporine. PMID- 1412794 TI - The effect of HLA-A,B matching in cadaver grafts. PMID- 1412796 TI - Antiphospholipid antibodies causing positive flow crossmatches and interfering with T-cell immunophenotyping. PMID- 1412795 TI - HLA-A, -B, and -DR matching contributes to graft survival in black recipients of renal allografts. PMID- 1412797 TI - Cytotoxic B-cell crossmatches: comparing three techniques. PMID- 1412798 TI - Toward identification of minor histocompatibility antigens in mouse and man. PMID- 1412799 TI - Cyclosporine quality assessment in Japan. PMID- 1412800 TI - Retrospective study of renal transplantation with cyclosporine (CyA) monotherapy- the importance of CyA blood trough levels on long-term graft survival. PMID- 1412802 TI - Long-term results with conversion from cyclosporine to azathioprine at 3 months after renal transplantation. PMID- 1412801 TI - Short-term cyclosporine conversion in living related donor renal transplantation- preliminary observations. PMID- 1412803 TI - Cytologic analysis of CyA nephrotoxicity: double vs triple drug therapy in kidney grafted patients. PMID- 1412804 TI - Impact of imipenem/cilastatin on cyclosporine metabolism and excretion. PMID- 1412805 TI - Ketoconazole in posttransplant triple therapy: comparison of costs and outcomes. PMID- 1412806 TI - Concomitant administration of cyclosporine and ketoconazole in renal transplant patients. PMID- 1412807 TI - Cyclosporine blood level monitoring by three specific methods; RIA H3, RIA I125, and fluorescence polarization: comparison of accuracy, cost, reproducibility and percent recovery. PMID- 1412808 TI - Cyclosporine dosage according to pharmacokinetic profiles leads to better graft and patient survival rates and a decrease in cyclosporine consumption. PMID- 1412809 TI - Rheologic complications of cyclosporine treatment and red cell membrane K+ and Ca++ transport. PMID- 1412810 TI - Long-term effects of cyclosporine on hemodynamic parameters of renal allograft recipients. PMID- 1412811 TI - Plasma exchange vs cyclosporine retrieval therapy in steroid-resistant acute rejection of renal allografts. PMID- 1412813 TI - Experience with administration of 15-deoxyspergualin in rejection in kidney transplant recipients. PMID- 1412812 TI - Low-dose dexamethasone--an alternative therapy for acute renal allograft rejection. PMID- 1412815 TI - Prospective trial of OKT3 for early prophylaxis of rejection in immunologic "high risk" renal transplant recipients: long-term results. PMID- 1412814 TI - Optimal dose of Minnesota antilymphocyte globulin for induction immunosuppression in cadaveric renal transplants. PMID- 1412816 TI - A new chimeric monoclonal CD4 antibody for prevention of rejection after heart transplantation. PMID- 1412818 TI - Successful living-related ABO incompatible renal transplant using the BIOSYNSORB Immunoadsorption Column. PMID- 1412817 TI - Safety and efficacy of BIOSYNSORB immunoadsorption column treatment. PMID- 1412819 TI - Long-term problems of renal transplantation. PMID- 1412820 TI - Renal transplantation and parenthood. PMID- 1412821 TI - Hyperreactivity against panel: a risk factor for renal transplant. PMID- 1412822 TI - Donor-specific transfusion in living-related renal transplants. PMID- 1412823 TI - Predictors for late allograft nephrectomy in the cyclosporine era. PMID- 1412824 TI - The detrimental effect of early rejection on long-term renal allograft outcome. PMID- 1412825 TI - The effect of successful renal transplantation on visual evoked potentials and brain stem auditory evoked responses. PMID- 1412826 TI - The influence of race and the impact of socioeconomic and clinical factors on primary renal allograft survival. PMID- 1412827 TI - Is mezlocilline prophylaxis effective in clinical renal transplantation? PMID- 1412828 TI - Single center renal transplant experience of oriental recipients with white donor kidneys. PMID- 1412830 TI - Complications in stable renal transplant recipients. PMID- 1412829 TI - Is Indian origin a risk factor in cadaveric renal transplantation? PMID- 1412831 TI - Spontaneous intestinal perforation in renal transplant patients. PMID- 1412832 TI - Utility of renal functional studies to evaluate mild elevation of serum creatinine in stable transplant patients. PMID- 1412833 TI - The influence of recovery of early function on long-term renal allograft outcome. PMID- 1412834 TI - Urinary protein patterns in kidney transplant patients. PMID- 1412835 TI - Chronic rejection and urinary acidification in kidney transplant patients. PMID- 1412836 TI - Polycythemia in renal transplant recipients. PMID- 1412837 TI - Hyperuricemia and gout in renal allograft recipients. PMID- 1412838 TI - Protein catabolic rate after renal transplantation. PMID- 1412839 TI - Renal transplantation in diabetic patients: a survey of 100 cases. PMID- 1412840 TI - Diabetes mellitus after renal transplantation. PMID- 1412841 TI - Postrenal transplant diabetes in conventional and cyclosporine regimens. PMID- 1412842 TI - Renal transplantation in patients with amyloidosis due to familial Mediterranean fever. PMID- 1412843 TI - Renal transplantation in cyclosporine-treated patients with end-stage lupus nephropathy. PMID- 1412844 TI - The results of transplantation of patients with amyloid nephropathy. PMID- 1412845 TI - Refractory hypertension in transplant recipients. PMID- 1412846 TI - Infections in kidney transplantation in Latin America. PMID- 1412847 TI - Twenty-four-year experience in kidney transplantation at one single institution in Mexico City. PMID- 1412848 TI - Transplantation in Mexico. PMID- 1412849 TI - Kidney transplantation in systemic lupus erythematosus: experience from a reference center in Mexico. PMID- 1412850 TI - Kidney transplantation in Alport's syndrome: experience of one center in Mexico. PMID- 1412851 TI - Malignant neoplasms in renal transplant patients: a 24-year experience. PMID- 1412852 TI - Twenty years of pediatric renal replacement therapy in the state of Rio Grande do Sul, Brazil. PMID- 1412853 TI - End-stage renal disease in the state of Rio Grande do Sul, Brazil. PMID- 1412854 TI - Organ harvesting program improves cadaver renal transplant at Sao Paulo University, Brazil. PMID- 1412855 TI - Morbidity and mortality among Australian aboriginal renal transplant recipients. PMID- 1412856 TI - Transplantation practices in the Philippines. PMID- 1412857 TI - Kidney transplantation in Cebu. PMID- 1412858 TI - Living related donor renal transplantation in Semarang, Indonesia (1985 to 1991). PMID- 1412859 TI - Kidney transplantation in Indonesia. PMID- 1412860 TI - Surgical complications of living unrelated kidney transplantations in a Third World country. PMID- 1412861 TI - Living related donor kidney transplantation in Sri Lanka. PMID- 1412862 TI - Sri Lankan experience with three immunosuppressive protocols in living related donor kidney transplantation. PMID- 1412863 TI - Renal transplantation in Singapore. PMID- 1412864 TI - Present status of transplantation in Japan. PMID- 1412865 TI - Organ transplantation practices in Taiwan. PMID- 1412866 TI - Renal transplantation in India. PMID- 1412867 TI - Rehabilitation after renal transplantation in a rural population of Rajasthan State, India. PMID- 1412868 TI - Experience of kidney transplantation in Bangladesh. PMID- 1412869 TI - End-stage renal disease in the native population of the United Arab Emirates. PMID- 1412870 TI - Review of surgical complications of renal transplantation in the Jeddah Transplant Program. PMID- 1412871 TI - Living related-cadaveric-living unrelated kidney transplants: a comparison study at King Fahad Hospital, Riyadh. PMID- 1412872 TI - Cadaveric transplantation in Saudi Arabia: a 5-year experience. PMID- 1412873 TI - Five-years' experience with cadaveric kidney transplantation at King Faisal Specialist Hospital and Research Center, Riyadh. PMID- 1412874 TI - Eleven years of renal transplantation in children (Israel). PMID- 1412875 TI - Triple-drug regimen for first kidney transplants in developing countries. PMID- 1412876 TI - Excellent results with imported cadaveric kidneys. PMID- 1412877 TI - Comparative results of second kidney transplantation. PMID- 1412879 TI - Assessment of attitudes toward cadaver donation at Tabriz Medical Science University. PMID- 1412878 TI - Living related donor kidney transplantation at a Turkish center. PMID- 1412880 TI - Chronic renal failure at the Lagos University Teaching Hospital: a 10-year review. PMID- 1412881 TI - Renal transplant odyssey. PMID- 1412883 TI - The incidence and etiology of chronic renal failure in the Republic of Slovenia. PMID- 1412882 TI - Transplant organization in Italy. PMID- 1412884 TI - Severe surgical complications after kidney transplantation. PMID- 1412885 TI - Parathyroidectomy before and after renal transplantation. PMID- 1412887 TI - Complex renal transplant for vascular reasons. PMID- 1412886 TI - Follow-up of 29 kidney transplant recipients having more than 20 years of functioning allografts. PMID- 1412888 TI - Donor polar kidney arteries: experience with 10 cases among 140 living-related kidney transplants. PMID- 1412889 TI - Renal transplants with multiple arteries. PMID- 1412890 TI - Renal artery stenosis in the transplanted kidney. PMID- 1412891 TI - Urological complications in 884 consecutive transplants. PMID- 1412892 TI - Renal transplant-related urologic complications (Philippine experience). PMID- 1412893 TI - Extravesical ureteroneocystostomies in kidney transplant: comparison between Lich Gregoir and Barry's technique in our first 50 kidney transplants (India). PMID- 1412894 TI - Management of vesicoureteral reflux in renal transplant recipients by endoscopic Teflon injection. PMID- 1412895 TI - Surgical alternatives in renal transplantation with unavailability of the lower urinary tract. PMID- 1412896 TI - Renal transplantation in patients with Chagas' disease: a long-term follow-up. PMID- 1412897 TI - Automated biopsy device for renal transplant monitoring. PMID- 1412898 TI - Color Doppler studies of the transplant renal artery in patients with allograft rejection--correlation with graft biopsy. PMID- 1412899 TI - Living-related and living-unrelated kidney transplantation using low-dose triple immunosuppression. PMID- 1412900 TI - Factors responsible for elimination of potential kidney donors in a living related donor kidney transplant program. PMID- 1412901 TI - Steroid withdrawal in HLA-nonidentical living-related donor transplant recipients. PMID- 1412902 TI - Living unrelated donor kidney transplantation. PMID- 1412904 TI - Cryptococcosis in renal transplant recipients. PMID- 1412903 TI - Unrelated living donor kidney transplant and developing countries. PMID- 1412905 TI - Renal transplantation and Chagas' disease. PMID- 1412906 TI - Special infections in organ transplantation in South America. PMID- 1412907 TI - Tuberculosis in renal allograft recipients. PMID- 1412908 TI - Tuberculous interstitial granulomatous nephritis in renal transplants: report of three cases. PMID- 1412909 TI - Is there a place for prophylaxis against tuberculosis following renal transplantation? PMID- 1412910 TI - Prevalence of hepatitis B, hepatitis delta, and human immunodeficiency virus infections in Omani patients with renal diseases. PMID- 1412911 TI - Liver disease in renal transplant recipients. PMID- 1412912 TI - Impact of renal transplantation on liver disease of diverse etiology. PMID- 1412913 TI - Safe use of acyclovir (Zovirax) in renal transplant patients on cyclosporine A therapy: case reports. PMID- 1412914 TI - Multiple respiratory tract infections with particular reference to immunocompromised patients. PMID- 1412916 TI - Infection in kidney transplantation recipients in Indonesia. PMID- 1412915 TI - Infections after kidney transplantation. PMID- 1412917 TI - Determination of the causes of fever in allograft recipients in west Iran (Bakhtaran). PMID- 1412918 TI - Fungal infections in renal allograft recipients. PMID- 1412919 TI - Infectious complications in renal allograft recipients. PMID- 1412920 TI - Bone banking and transplantation in developing countries. PMID- 1412921 TI - Malignancy following renal transplantation. PMID- 1412923 TI - The necessary requirements for the development of a national liver transplant programme. PMID- 1412922 TI - Increased risk of malignant tumors in renal transplant recipients receiving cyclosporine. PMID- 1412924 TI - Initial experience with liver transplantation at a private university hospital in Spain. PMID- 1412925 TI - Initiation of a liver transplant program in South Africa. PMID- 1412926 TI - Liver splits--the answer to a low donor pool? PMID- 1412927 TI - Segmental (partial) liver transplantation from a living donor. PMID- 1412928 TI - MEGX as a test of donor liver function. PMID- 1412929 TI - Causes of death after pediatric liver transplantation. PMID- 1412930 TI - Reoperative procedures following pediatric liver transplantation. PMID- 1412931 TI - Liver retransplantation--indications, frequency, results. PMID- 1412932 TI - Living related and cadaver donor liver transplantation. PMID- 1412933 TI - Importance of body temperature control during liver transplantation. PMID- 1412934 TI - Serial changes of h-HGF and IL-6 in living-related donor liver transplantation with special reference to their relationship to intraoperative portal blood flow. PMID- 1412935 TI - Semiquantitative histologic evaluation of the liver in patients after liver transplantation. PMID- 1412936 TI - Subcellular lesions of the biliary tract in human liver transplants incurred during preservation. PMID- 1412937 TI - Effect of initial perfusion with lactated Ringer's solution in 24-hour canine liver preservation with University of Wisconsin solution. PMID- 1412938 TI - Cyclosporine hepatotoxicity and cold ischemia liver damage. PMID- 1412939 TI - Color flow Doppler imaging during epoprostenol (PGI2) therapy of primary nonfunction following liver transplantation. PMID- 1412940 TI - New technique for veno-venous bypass in a canine liver transplant model. PMID- 1412941 TI - Animal model for reduced left liver lobe transplantation. PMID- 1412942 TI - Changes in prostaglandin E2 during and after liver transplantation in pigs. PMID- 1412943 TI - Fetal islet transplantation. PMID- 1412944 TI - Fetal islet transplantation in China. PMID- 1412946 TI - Scale production of porcine isletlike cell clusters and xenotransplantation. PMID- 1412945 TI - Human fetal pancreata for islet cell research: the Singapore experience. PMID- 1412947 TI - The HeartMate: a left ventricular assist device as a bridge to cardiac transplantation. PMID- 1412948 TI - Mechanical circulatory support: a necessary adjunct to a cardiac transplantation service. PMID- 1412949 TI - Heart transplantation: additional criteria for patient selection. PMID- 1412950 TI - Cardiopulmonary transplantation service establishment in the 1990s: Australia--a developing country? AB - 1. A National Transplantation Service has been established at the Alfred Hospital performing more than 50 transplants per year. 2. Increased access to transplantation technology has facilitated an improvement in national population servicing from 2.7 to 6.2 transplants per million population per year. National funding of A$4.062 million per year has been secured. 3. Basic research into organ preservation has facilitated transcontinental organ procurement. 4. An active lung transplantation program has been established synchronous with the cardiac transplant service activities. 5. MCS program establishment has paralleled clinical transplantation activities. 6. Budget management and cost containment has been achieved through rationalisation of management protocols. PMID- 1412951 TI - Clinical and electrophysiological characteristics of vascular rejection after cardiac transplantation. PMID- 1412952 TI - Long-term function of Euro-Collins--preserved human cardiac allografts. PMID- 1412953 TI - Survival and intermediate-term effects of cyclosporine-treated heart transplantation. PMID- 1412954 TI - Echo-controlled endomyocardial biopsy after orthotopic and heterotopic heart transplantation. PMID- 1412955 TI - Aortic aneurysms after heart transplantation. PMID- 1412956 TI - Exercise capacity after combined heart-lung transplantation. PMID- 1412957 TI - Urinary thromboxane B2 excretion during acute rejection in cyclosporine-treated experimental lung allotransplantation. PMID- 1412958 TI - Tracheobronchial blood flow after a modified canine lung autotransplant: effect of omental wrapping. PMID- 1412959 TI - Australian Bone Marrow Donor Registry: cost-effectiveness and ethnic considerations. PMID- 1412960 TI - Changing application and problems of bone marrow transplantation in children. PMID- 1412961 TI - Infections in bone marrow transplant patients: use of reverse-barrier isolation. PMID- 1412962 TI - Corneal graft rejection: incidence, manifestation, and interaction of clinical subtypes. PMID- 1412963 TI - The establishment and development of an international tissue transplant program: Bio Implant Services. PMID- 1412964 TI - The non-heart-beating kidney donor: of any help in developing countries? PMID- 1412965 TI - Cyclosporine immunosuppression in non-heart-beating cadaver donors. PMID- 1412966 TI - The influence of cold ischemia and donor age on renal allograft outcome in the cyclosporine era. PMID- 1412967 TI - The organisation of cadaver multiple organ donation: a critical issue for establishing and maintaining successful transplantation programs. PMID- 1412968 TI - The role of the operating theatre in organ transplantation. PMID- 1412969 TI - The role of the media in cadaver transplantation in a developing country. PMID- 1412970 TI - The evolution of transplant coordinators in Australia. PMID- 1412971 TI - Organizational structures as the basis for successful kidney transplantation in Germany. PMID- 1412972 TI - Enhancement of organ procurement by the National Program of Cadaveric Organ Transplantation in Mexico. PMID- 1412973 TI - Public attitudes toward organ donation in Saudi Arabia. PMID- 1412974 TI - Problems encountered in the development of organ transplantation in Japan. PMID- 1412975 TI - Development of a local network for liver transplantation in the Kinki region of Japan: two-year experience of the Recipient Selection Committee. Recipient Selection Committee Members of the Kinki Network for Liver Transplantation. PMID- 1412976 TI - How to increase cadaver organ donation in Japan: a transplant recipients' approach. PMID- 1412977 TI - Strategy for a public education campaign to enhance altruistic donation of kidneys for transplantation in India. PMID- 1412978 TI - Outcome of brain-dead patients in Jeddah Kidney Center. PMID- 1412979 TI - Opinion poll regarding knowledge, attitudes, and suggestions for developing a cadaver donor program. PMID- 1412980 TI - Funding the bridge to renal transplantation: the National Kidney Foundation of Singapore model. PMID- 1412981 TI - The potential for cadaver organ retrieval in Singapore. PMID- 1412982 TI - Cadaver organ donors in Singapore. PMID- 1412983 TI - Difficulties of foreigners seeking transplantation in the United States. PMID- 1412985 TI - Multiorgan harvesting from heartbeating donors in Turkey. PMID- 1412984 TI - Ultrastructural aspects of the iliac arteries of multiorgan donor preserved in University of Wisconsin solution for 48 hours. PMID- 1412986 TI - Cadaveric multiple organ removal in Rio Grande do Sul, Brazil. PMID- 1412987 TI - Donor factors and liver transplantation. AB - There are thus many factors that may affect the suitability of a donor liver for transplantation, and a reliable, objective method of determining whether or not a liver is likely to function adequately after transplantation is urgently required. At the present time, however, the decision to use a particular donor liver remains a matter of clinical judgement. This decision will inevitably be influence both by the general availability of donor organs and by the urgency of recipient need at the time the liver becomes available, but should nevertheless be based primarily on an appreciation of the donor factors described above. PMID- 1412988 TI - Immediate and ongoing needs of donor families. PMID- 1412989 TI - Nonrelated donors and commercialism: a historical perspective. PMID- 1412990 TI - Current risks of organ commerce. PMID- 1412991 TI - Rewarded gifting: is it ever ethically acceptable? PMID- 1412993 TI - Social and ethical aspects of organ donation. PMID- 1412992 TI - Toward an affordable ethic. PMID- 1412994 TI - Ethical dilemmas in transplantation. PMID- 1412995 TI - Ethics in organ procurement in Turkey. PMID- 1412996 TI - Public attitudes to organ donation in South Africa. PMID- 1412997 TI - Cadaver transplantation as an ethical and cost-effective alternative to living donor transplantation: the Spanish experience. PMID- 1412998 TI - Extending organ availability with living-nonrelated renal transplants. PMID- 1412999 TI - Sale of kidneys for transplantation: attitudes of the health-care profession and the public. PMID- 1413000 TI - Developing countries as the major future source of living donor renal transplants. PMID- 1413001 TI - Buying a kidney: the easy way out? PMID- 1413002 TI - Organ donation and transplantation: a Christian viewpoint. PMID- 1413003 TI - Organ donation and transplantation--a Muslim viewpoint. PMID- 1413004 TI - Legal aspects of transplantation--judicial issues. PMID- 1413005 TI - The function of legislation in transplant programs. PMID- 1413006 TI - Legal aspects of transplantation: emerging trends in international action and national legislation. PMID- 1413007 TI - Legal aspects of transplantation in Argentina: a model to be considered for developing countries. PMID- 1413008 TI - Economics of renal rehabilitation in Pakistan: a case for increasing transplantation activity. PMID- 1413009 TI - Costs and financing of kidney transplantation in the United States. PMID- 1413010 TI - Creation of low-cost model of renal transplantation suitable for developing countries. PMID- 1413012 TI - Organ procurement: supply, demand, and ethics. PMID- 1413011 TI - Supply and demand for transplantable organs: the ethical perspective. PMID- 1413013 TI - Supply, demand, and ethics of organ procurement: the medical perspective. PMID- 1413014 TI - The body as property: some philosophical reflections. PMID- 1413015 TI - Need, demand, and supply in organ transplantation. PMID- 1413016 TI - Required request: what difference has it made? PMID- 1413017 TI - Psychological impediments to procurement. PMID- 1413018 TI - The problem of organ donation in minorities: some facts and incomplete answers. PMID- 1413019 TI - Postmortem and living organ donation in Europe: transplant laws and activities. PMID- 1413020 TI - The case for presumed consent to transplant human organs after death. PMID- 1413021 TI - Presumed consent to organ transplantation: a different perspective. PMID- 1413022 TI - The moral duty to contribute and its implications for organ procurement policy. PMID- 1413023 TI - Organ transplantation: duty reconsidered. PMID- 1413024 TI - Should receiving depend upon willingness to give? PMID- 1413025 TI - More blessed to give than to receive? PMID- 1413026 TI - My kingdom for a kidney? PMID- 1413027 TI - The case for commerce in organ transplantation. PMID- 1413028 TI - The case against buying organs and a futures market in transplants. PMID- 1413029 TI - Future markets: claims and meanings. PMID- 1413030 TI - Inducements for donation: benign incentives or risky business? PMID- 1413031 TI - Rewarded gifting. PMID- 1413032 TI - Used body parts: buy, sell or swap? PMID- 1413033 TI - Unrelated living donors: should they be used? PMID- 1413034 TI - Anencephalic infants as organ donors. PMID- 1413035 TI - High-risk donors: diabetics, the elderly, and others. PMID- 1413036 TI - Liver transplantation using living donors. PMID- 1413037 TI - Xenografts. PMID- 1413038 TI - General principles for allocating human organs and tissues. PMID- 1413039 TI - Ethics of organ transplantation from living donors. PMID- 1413040 TI - First report of an Australian randomised trial comparing cyclosporine+prednisolone with cyclosporine+azathioprine and cyclosporine+azathioprine+prednisolone in renal transplantation. PMID- 1413041 TI - Live donor renal transplantation with low-dose triple immunosuppression. PMID- 1413042 TI - The outcome of children transplanted with either pediatric or adult cadaver donor kidneys. PMID- 1413043 TI - Prostaglandin E1 therapy in orthotopic liver transplantation recipients: indications and outcome. PMID- 1413044 TI - Liver allograft rejection: analysis of OKT3 rescue therapy. PMID- 1413045 TI - Living related liver transplantation. PMID- 1413046 TI - Human resistance artery reactivity is altered by liver transplantation and treatment with cyclosporin A. PMID- 1413047 TI - Psychosocial adjustment to illness: quality of life following liver transplantation. PMID- 1413048 TI - Diltiazem co-administration reduces cyclosporine toxicity after heart transplantation: a prospective randomised study. PMID- 1413049 TI - Mini-dose trimethoprim with sulphamethoxazole prevents pneumocystis and toxoplasmosis infections after heart transplantation. PMID- 1413050 TI - Combined heart-lung transplantation including the "domino" donor procedure in the single lung transplant era. PMID- 1413051 TI - Prophylactic use of GM-CSF in pediatric marrow transplantation. PMID- 1413052 TI - Genetic factors influence the development of acute graft-versus-host disease in adults undergoing allogeneic bone marrow transplantation. PMID- 1413053 TI - Can the demand for cadaver kidneys be met? PMID- 1413054 TI - Cadaver kidneys from elderly and other "suboptimal" donors: can we afford to discard a scarce resource? PMID- 1413055 TI - The induction of tolerance to small bowel transplants in rats. PMID- 1413056 TI - Is thymic epithelium inherently immunogenic? PMID- 1413057 TI - Age at marrow transplantation is critical for successful treatment of canine fucosidosis. PMID- 1413058 TI - Stereoscopic analysis of focal interstitial infiltrate in a model of chronic rejection. PMID- 1413059 TI - A microsurgical rat model for aortic valve allografts. PMID- 1413060 TI - Xenotransplantation of fetal pig proislets in anti-CD4-treated diabetic NOD/Lt mice. PMID- 1413061 TI - Anti-CD3 monoclonal antibody prolongs survival of fetal pig pancreas grafts in NOD mice. PMID- 1413062 TI - Destruction of xenografts but not allografts within cell impermeable membranes. PMID- 1413063 TI - The MEGX test as a measure of liver viability in an isolated liver perfusion circuit. PMID- 1413064 TI - Castanospermine, an inhibitor of glycoprotein processing, prolongs pancreaticoduodenal allograft survival. PMID- 1413066 TI - The transplantation of segmental pancreas isografts in nonobese diabetic mice. PMID- 1413065 TI - CD8+ T-cell removal reduces survival of minor antigen mismatched islet allografts (CBA-->C3H) in mice treated with anti-CD4 monoclonal antibody. PMID- 1413067 TI - Destruction of transplanted beta cells into diabetic NOD mice is not mediated by antibody alone. PMID- 1413068 TI - Immunosuppression by aminopterin or idarubicin conjugated to anti-CD8 in the mouse heart allograft model. PMID- 1413069 TI - The anticoagulants protein C and protein S display potent antiinflammatory and immunosuppressive effects relevant to transplant biology and therapy. PMID- 1413070 TI - Use of an anti-LFA-1 antibody in renal allograft rejection in sheep. PMID- 1413071 TI - Mechanism of a clinically relevant protocol to induce tolerance: peritransplant spleen cells plus cyclosporine suppress IL-2 and IFN-gamma production. PMID- 1413072 TI - Levels of cytokine expression in rat liver allograft rejection compared to allograft tolerance. PMID- 1413073 TI - Identification of cytokine protein expression in human liver allograft rejection: methods development and expression of IL-1 beta, IL-6, IFN-gamma, and basic fibroblast growth factor. PMID- 1413074 TI - In vivo evidence for the Th1/Th2 paradigm: oral alloantigen-induced modulation of accelerated allograft rejection is associated with dense intragraft IL-4. PMID- 1413075 TI - Cells, cytokines, adhesion molecules, and humoral responses in a rat model of chronic renal allograft rejection. PMID- 1413076 TI - Lymphokine production in vivo in a murine graft-versus-host reaction. PMID- 1413077 TI - Adhesion molecule expression: a comparison of human blood dendritic cells, monocytes, and macrophages. PMID- 1413078 TI - Cellular protein profiles of human dendritic cells: a comparative study. PMID- 1413079 TI - CD16dim and CD16bright subpopulations of human natural killer cells. PMID- 1413080 TI - Functional recombinant soluble human Fc gamma RII. PMID- 1413081 TI - Serum soluble Fc gamma RII levels in dialysis and renal transplant recipients. PMID- 1413082 TI - Functional characterisation of alternatively spliced CD46 cytoplasmic tails. PMID- 1413083 TI - Tissue-specific expression of CD46 isoforms. PMID- 1413084 TI - Ancestral haplotypes predict EC-1 alleles. PMID- 1413085 TI - Keeping an eye on the I site: imidazoline-preferring receptors. PMID- 1413086 TI - Cell volume and hormone action. PMID- 1413087 TI - Neuroendocrine actions of endothelins. AB - Endothelins are produced in neuronal, pituitary and peripheral endocrine cells, and act through specific endothelin receptors (predominantly the ETA subtype) that are widely distributed in the neuroendocrine system. Endothelin receptors share a common signal transduction pathway with other Ca(2+)-mobilizing receptors, and endothelins induce IP3 and diacylglycerol production, and elevation of [Ca2+]i in many cell types, with kinetics similar to the cognate agonists. As reviewed here by Stanko Stojilkovic and Kevin Catt, the physiological consequences of endothelin-mediated cell signalling are relevant to the control of several neuroendocrine and endocrine activities including neuropeptide release, pituitary hormone secretion, gonadal and placental function, fluid and electrolyte homeostasis and glycogenolysis. PMID- 1413088 TI - Recent advances in the electrophysiological characterization of 5-HT3 receptors. AB - 5-HT3 receptors are ligand-gated, cation-selective ion channels, mediating membrane depolarization and neuronal excitation. Established and potential therapeutic applications of selective 5-HT3 receptor antagonists, coupled with the localization of this receptor subtype within discrete areas of the CNS, have resulted in an intensification of research in this area. In this review, Jeremy Lambert and colleagues summarize recent developments in the electrophysiological characterization of 5-HT3 receptors, and comment upon the unresolved issue of 5 HT3 receptor heterogeneity. PMID- 1413089 TI - Ca(2+)-induced Ca2+ release and its modulation by cyclic ADP-ribose. PMID- 1413090 TI - New insights into activation of the steroid hormone receptor superfamily. AB - For many years the prevailing view of how steroid hormone receptors exert their effects on gene transcription has been that these intracellular receptor proteins, upon association with their specific cognate ligands, undergo a transformation to a state where they are capable of interacting with chromatin and regulating the transcription of specific genes. It has become implicit dogma in the field of biochemical endocrinology that receptor activation is absolutely dependent upon this ligand-binding event. However, recent studies described here by Bert O'Malley and colleagues have shown that certain members of the steroid hormone receptor superfamily can be activated in a totally ligand-independent manner by a cell membrane receptor agonist, the neurotransmitter dopamine. PMID- 1413091 TI - Designing therapeutically effective 5-lipoxygenase inhibitors. AB - Metabolism of arachidonic acid by the enzyme 5-lipoxygenase leads to the formation of a group of biologically active lipids known as leukotrienes. Peptidoleukotrienes are powerful bronchoconstrictor agents while leukotriene B4 is a potent chemotactic agent for a variety of leukocytes. In view of these properties, leukotrienes have been proposed as important mediators in allergic and inflammatory disorders, and inhibitors of 5-lipoxygenase, by blocking leukotriene synthesis, have therapeutic potential in a range of diseases including arthritis and asthma. This review by Rodger McMillan and Ed Walker summarizes the biology of leukotrienes and the current knowledge of the mechanism of 5-lipoxygenase, providing a framework for consideration of the discovery, development and clinical status of drugs in the three major classes of 5 lipoxygenase inhibitors: 'redox' inhibitors, iron ligand inhibitors and 'non redox' inhibitors. PMID- 1413092 TI - Diet, diseases and cancer. PMID- 1413093 TI - An update on viral hepatitis. PMID- 1413094 TI - Spastic colitis and irritable bowel syndrome: which expression is prevalent? (A review of 120 cases). AB - Spastic Colitis (SC) of the fifties has been deleted and included in the Irritable Bowel Syndrome, as inflammation is not present, and the disturbed intestinal motility may involve the small and large intestine. With the advent of colonoscopy, we could investigate this generalized common term. Between 1983 and 1988 we have studied 120 documented cases of SC by colonoscopy with multiple biopsies. In every patient, we relied on consecutive procedures to confirm the diagnosis. They included: Stool examination, barium enema, small bowels series, colonoscopy with multiple biopsies. Serological diagnosis of Amebiasis has been applied to 41 patients only. With a normal small bowels, barium enema revealed a severe spasm of the whole colon, or a segmental spasm in one part of the colon. In 53 cases (44%,) we have noted virtual absence of haustra in the tubular descending colon. Colonoscopy in all cases has revealed an active contraction with some congestion of the mucosa or hyperemia. Different degrees of inflammatory reaction shown on multiple biopsies make the diagnosis of SC in these cases more relevant. In the Afro-Asiatic countries where amebiasis is endemic, SC is to be considered, as colonoscopy is proving the prevalence of congested or inflammatory process in the colonic mucosa, even when stool examination is repeatedly negative for amebiasis. PMID- 1413095 TI - Heller's cardiomyotomy after failed pneumatic dilatation for achalasia cardia- operative pitfalls. AB - A female aged 46, with achalasia cardia had no relief of dysphagia after pneumatic dilatation done twice. At surgery the muscle fibres were found disrupted, with submucosal adhesions and friable mucosa. Heller's cardiomyotomy could not be done. Repair similar to Mickulicz pyloroplasty was done. PMID- 1413096 TI - Indian diets and carcinogenesis. PMID- 1413097 TI - Training in gastroenterology. PMID- 1413098 TI - Imaging techniques in diagnosis of hepatic lesions. PMID- 1413099 TI - Radiologic diagnosis of hydatid disease of the liver. PMID- 1413101 TI - The surgical pathology of colorectal carcinomas in Nigerians. AB - This paper presents a 10-year experience on the examination of surgical specimens of colorectal carcinomas in Nigerians. Colorectal carcinomas were found to constitute about 80% of all cases of large bowel malignancy. The Male: Female ratio was 2.28:2. Most of the cases (65.9%) were 50 years or younger and the peak incidence was in the 41-50 year age group. The site distribution in order of frequency was recto-sigmoid area (57.3%), descending colon (23.2%), caecum (12.2%) ascending colon and transverse colon 3.7% each. Seventy-three percent of the tumours were well differentiated adenocarcinomas while 15.9% were poorly differentiated. Mucinous carcinoma and signet ring carcinoma were found in 7.3% and 3.7% respectively. There was colonic metastasis in 54.9% of cases and 20.8% had distant metastases at initial surgery. Associated lesions were villous adenoma, 24.4%, Tubular adenoma-17.1%, amoebiasis 6.1% and schistosomiasis, 3.7%. The above observations together with those of previous authors suggests a difference in the biology of colorectal carcinomas in the tropics. The association with chronic granulomatous diseases, in particular, may be indicative of an entirely different oncogenic mechanism in their development in the tropics. PMID- 1413100 TI - Typhoid and paratyphoid fever: a retrospective study. AB - Sixty-eight proved cases of typhoid and paratyphoid fever were reviewed in a retrospective study covering 5 years (1986-1990). Patients within the age range of 10 to 39 years constituted 82.3 per cent of cases and there was equal incidence in both sexes. The mean duration of illness before presentation was 9.67 days. The major clinical features were fever (97%), abdominal tenderness ( 9.4%), headache and abdominal pain (70.58%) each). Intestinal perforation was the commonest complication (27.9%) with a male preponderance (M:F-3:1). Perforation occurred after the first week of illness in 73.7 per cent of cases. Fourteen out of the nineteen patients who perforated were not on therapy at the time of perforation and they constituted 80 per cent of those cases of mortality in which perforation played a role. Surgical management of perforation gave better results than conservative management (mortality rates of 16.7% and 40% respectively). Salmonella was sensitive to Chloramphenicol in all the cases where the organism was grown. There were 10 recorded deaths (14.9%) of whom 60 per cent (i. e. 6 patients) presented after two weeks of illness. PMID- 1413102 TI - Evaluation of antacid gel preparations available commercially in the Indian market. AB - A scoring system based on the neutralising capacity, cost efficiency and time of buffering of twenty four commercially available antacid gels was analysed. A gel scoring eight out of the ten points was considered as the best antacid. The study provides a practical guide in choosing a quick neutralizing and low cost antacid gel. PMID- 1413103 TI - Peroperative cholangiogram--routine or selective results of a prospective study. AB - Peroperative cholangiography (POC) performed as a routine during cholecystectomy for cholelithiasis was evaluated in 102 patients. POC was normal 93 patients. Nine patients had abnormal POCs: 5 were true positive--CBD stones (4) and sphincteric fibrosis (1): 4 were false positive--air bubbles (2) and sphincteric spasm (2). Preoperative indication of CBD stones were present in 12 patients-5 of these had abnormal POC (4 true positive and 1 false positive). CBD exploration was avoided in 7 patients with normal POC. Ninety patients did not have any preoperative indication of CBD stones-4 of these had abnormal POC (1 true positive and 3 false positive). None of the patients with a normal POC had any clinical evidence of residual stones on follow up for one year. POC did not help in any case to delineate biliary ductal anatomy. Routine POC during cholecystectomy should be abandoned and should be performed selectively in patients suspected to have CBD stones only to avoid a negative CBD exploration. PMID- 1413105 TI - Views on "training in gastroenterology in India". PMID- 1413104 TI - Malignant carcinoid tumor of the gallbladder: a case report and review of literature. AB - Carcinoid of the gallbladder and bile ducts is a rare tumor. Till date 20 cases have been reported. Here we report one more case and review all 21 cases collectively. The tumor affects elderly patients of either sex equally. Surgical obstructive jaundice (SOJ), followed by abdominal symptoms were the commonest presenting complaints. None of the patients presented with carcinoid syndrome. Bile duct carcinoids presented significantly earlier than gallbladder carcinoids because of strategic location causing SOJ. Gallstones were present only in 3 cases. Fifty per cent of these tumors were malignant, with liver followed by bone as the commonest site of metastasis. Surgery has been the mainstay of the treatment of these lesions. Old age, jaundice and metastasis at presentation and location of carcinoid in bile duct were found to be bad prognostic factors. In the absence of these features overall survival after surgical procedures like radical cholecystectomy was encouraging enough to undertake the surgical challenge. PMID- 1413106 TI - [Antivitamin activity of oxythiamine disulfide nicotinate]. AB - The B1-antivitamin activity of oxythiamine disulphide nicotinate has been determined in experiments on albino mice and it is shown that in the liver this derivative exerts the equal action while in the blood and heart--a more profound and prolonged inhibitory action on the transketolase activity in comparison with oxythiamine disulphide. Like the initial compound oxythiamine disulphide nicotinate does not penetrate through hemato-encephalic barrier and does not inhibit the brain transketolase. PMID- 1413107 TI - [Effect of ethanol and ethylene glycol on the circadian rhythm of adenylic nucleotide levels in muscles]. AB - The 24-hour's changes in ATP content in the gastrocnemiuses of intact rast are not significant. Both the ADP and AMP content is subjected to 24-hour's variations. It reaches its maximum within the time period from 12 to 15 o'clock p.m. for ADP and at 18 o'clock p.m. for AMP. Intragastric administration of ethanol and ethylene glycol to rats in a dose of 1/3 LD50 once per 24-hour period at 9 a. m. during a 7-days-long period dramatically changes the 24-hour's rhythm of adenylic nucleotide content in the rat gastrocnemius. It has been found that ethanol increases the average 24-hour's content of ATP, but decreases that of ADP. It increases the range of their 24-hour period variations and changes the acrophase. Ethylene glycol decreases the average 24-hour content of the both ATP and ADP, but it increases that of AMP. It changes their acrophases and increases the ranges of 24-hour-period variations of ATP. PMID- 1413108 TI - [Respiratory and detoxication activity of two fractions of hepatocytes isolated by a non-enzymatic method]. AB - Slow centrifugation of isotonic sucrose medium containing the suspension of hepatocytes, obtained after disaggregation of liver, which has been preliminarily perfused by EDTA solution, results in the formation of two fractions of cells of different colour. Fraction 1 contains intact and metabolically active hepatocytes. Cells of fraction 2 have a damaged membrane, but they are capable of realizing biotransformation of xenobiotics in the presence of exogenous NADPH as well as maintaining efficiency of oxidative phosphorylation of mitochondria under the transfer to the medium simulating cytoplasm. PMID- 1413109 TI - [Effect of sodium nitrite poisoning on the activity of enzymes of anti-oxidant protection and peroxidation processes in mouse erythrocytes]. AB - The intoxication of white mice with sodium nitrite results in the decrease of red cell superoxide dismutase (SOD) and catalase activity. The glutathione peroxidase activity is the same as in the control group. The level of red cell lipid peroxidation in the group of mice that receive sodium nitrite is higher as compared to the control group. After the intoxication the total activity of glucose-6-phosphate dehydrogenase and dehydrogenase of 6-phosphogluconate as well as the activity of glutathione reductase are higher than in the control group. The level of SH-groups and reduced glutathione is higher in the group of mice that receive sodium nitrite in comparison with the control group. PMID- 1413110 TI - [Biochemical criteria for assessment of the population status of the northern birch mouse in technologic pollution]. AB - Energy metabolism and microsomal oxidation in the liver of meadow mice caught near a source of technogenic pollution (0.5 km from the enterprise) were studied for 2 years for their peculiarities. Intensification of oxidative processes of succinic acid in the liver mitochondria and a tendency to a decrease of glycolysis in the liver homogenates were observed. Under conditions of technogenic pollution in liver of animals the level of lipid peroxidation and rate of aniline metabolism increase. Activation of the processes of aminopyrine metabolism took place in the meadow mice liver only for one season. The next year the rate of aminopyrine metabolism in the animals liver was lower. This is explained by the system inhibition under the effect of technogenic factors. Therefore, the investigation of biochemical indices is used to indicate the unfavourable effect of technogenic factors in the natural populations of small rodents. PMID- 1413111 TI - [Mathematical modelling of charge properties of protein molecules]. AB - A procedure of theoretical determination of the dependence of protein molecule charge on the medium pH has been developed. The suggested procedure allows calculating the protein pI value, the molecule charge at the definite pH value, as well as the corresponding values for the protein molecule. Calculations for insulin, apo A-I and apo A-II molecules have been carried out. Calculated pI values are equal to 5.25, 5.64 and 4.86, respectively. A comparison of the theoretical curves and experimental data allows obtaining information of the molecule structure. Carboxyl groups with abnormally high pK values are discovered, that, probably, indicates to the direct interaction of two COOH groups. A supposition is made on the most probable arrangement of the functional fragments in apo A-I and apo A-II molecules. PMID- 1413113 TI - [Comparative analysis of spatial organization of myoglobins. II. Secondary structure]. AB - An analysis of probability of distribution curves of alpha-helical sites and bends of polypeptide chains of myoglobins in half-water mammals (beaver, nutria, muskrat, otter) carried out in comparison with those of myoglobins of the horse and Sperm whale (X-ray diffraction analysis has revealed their tertiary structure) has revealed a coincidence of the secondary structure sites end bends of the chain in the studied respiratory hemoproteins of muscles. Despite a considerable number of amino acid substitutions the profiles of alpha-helicity and B-bends of the compared proteins are practically identical. This indicates to the "resistance" of the probability curves to amino acid substitutions and to retention of the tertiary structure of myoglobins in evolutionary remote species of the animals. PMID- 1413112 TI - [Comparative analysis of the spatial organization of myoglobins. I. Hydrophobicity profiles]. AB - Hydrophobicity profiles of myoglobins in the animal species far remote in the evolutionary series are considerably similar. A complete coincidence as to the arrangement of hydrophobic zones along the polypeptide chain in myoglobins of the compared species (from a man to mollusc) is revealed at the beginning of alpha helix of B-segment and in the area corresponding to a cluster which embodies a heme- bound water molecule, distal histidine E7 being directed to this cluster. The mollusc myoglobin with two absent (as compared to myoglobins of other species) hydrophobic sites differs in the profile of hydrophobicity most of all. It is supposed that hydrophobic nuclei forming the heme circumference create a globule "skeleton" thus pre-setting general spatial structure of the myoglobin molecule, which is very significant for its functional activity. PMID- 1413114 TI - [Anti-oxidant system of blood plasma]. AB - Recent data available in literature and the author's data about the state of the antioxidant protection of the blood plasma have been generalized. The role of superoxide dismutase as the basic compound of the antioxidant system is discussed. The character of individual macromolecules (transferrin, ceruloplasmin, albumin) which have shown nonenzymatic specific antioxidant properties is presented. Possible mechanisms of biological activity of some antioxidants have been examined. PMID- 1413115 TI - [Role of the K4 and K5 plasmin heavy chain kringles in the fibrin clot structure destruction]. AB - A comparative analysis of the rates of polymeric fibrin structure destruction by plasmin (Pm) and its proteolytic derivatives such as Val354-plasmin (c-Pm), Val442-plasmin (m-Pm) and Lys530-plasmin (mu-Pm) has been undertaken. It was shown, that Pm, c-Pm, m-Pm and mu-Pm at equal proteolytic activity, have dissolved fibrin clots with relative rates 40.3:38.0:4.6:1.0 correspondingly. The Pm, m-Pm and mu-Pm relative rates were changed by epsilon-aminocaproic acid to 4.6:1.5:1.0 correspondingly. In this case fibrin clot destruction time was increased for Pm and m-Pm and was not changed for mu-Pm. The rates of fibrinogen hydrolysis were nearly equal for these forms of enzyme. It was suggested, that the specific interactions between plasmin K4 and K5 kringles and solid phase fibrin substrate determine the polymer fibrin structure destruction rate. PMID- 1413116 TI - [Level and correlation of metabolites of NAD(P)+-dependent dehydrogenase systems in newborn calf tissues in acute diarrhea]. AB - Substantial disorders of redox and energetic processes are observed in the newborn calf tissues which is evidenced by changes in glucose, lactate oxalo acetate, malate, citrate, alpha-ketoglytarate and glutamate concentrations, as well as in activity of lactate dehydrogenase and gamma-glutamyltransferase, succinate dehydrogenase and alkaline phosphatase and correlations of (NAD(p)/NAD(P)H) in blood cytoplasm and liver and kidney mitochondria. PMID- 1413117 TI - [Effect of stress factors on carboxypeptidase H activity in areas of the rat brain]. AB - It is established that carboxypeptidase H activity increases as affected by various stress factors in the rat brain departments. The increase of the enzyme activity because of the emotional-pain stress is of continuous character. Possible role of carboxypeptidase H in the development of the stress response is discussed. PMID- 1413119 TI - [Immunomodulating effect of ecdysterones]. AB - Ecdysterone, its 20-desoxy-derivative alpha-ecdysone, their 2-desoxy-derivatives ecdysterone 2, 3, 22-triacetate and preparation BTI-4 have been studied for their effect on [3H]-thymidine incorporation in different populations of animal and human lymphocytes. It is shown the ecdysteron and its analogs in concentrations of 10(-12)-10(-5) M take considerable stimulating effect on DNA biosynthesis in animal lymphocytes activated by polyclonal mitogens. The concentration of ecdysterone being increased to 10(-4) m one can observe complete inhibition of activating effect of polyclonal mitogens. Effect of the studied ecdysteroids did not considerably depend on their structure. In case of splenocytes the stimulating effect of ecdysterone on DNA biosynthesis is less expressed than in the case of activated thymocytes. Ecdysterone was established to have considerable inhibiting effect on DNA biosynthesis in the culture of activated Con A cells of lymphocytes in the peripheral blood of healthy donors. PMID- 1413118 TI - Effects of compound RU38486 on growth and lipid biosynthesis in glucocorticoid sensitive human leukemia line CEM-C7. AB - Glucocorticoid sensitive human lymphoblastoid cells CEM-C7 were examined for the effects of antiglucocorticoid RU38486 on the prevention of early dexamethasone induced changes, including reduced cell growth, cell shrinkage and fragmentation, decrease in cell plating efficiency and incorporation of acetate into cellular lipids. When RU38486 was added no later than 24 hours after the addition of dexamethasone, it prevented the inhibition of [14C]acetate incorporation into nonsaponifiable lipids, partly reversed the decrease in plating efficiency and reduced cell fragmentation. In addition, the accumulation of dolichols in the nuclei of dexamethasone-treated cells was abolished by RU38486. These results indicate that glucocorticoid-induced changes in cellular lipids are receptor dependent and may be linked to the initiation of the apoptotic cascade. PMID- 1413120 TI - [Change in concentration of cholesterol and lipoprotein fractions of rabbit blood serum in the dynamics of hypercholesterolemia]. AB - Three quantitatively different periods have been detected as a result of 21-week monitoring of blood serum total cholesterol at hypercholesterolemia in rabbits. The first of them (4th week) ends by a relative decrease of cholesterol concentration: the second one (4th-13th weeks) is characterized by its sharp increase; in the third period (13th-21st weeks) the sterol accumulation slows down. Concentration variations of all main lipoprotein fractions are observed in each of the above periods. Their specific features enable us to suppose that in the first period the cholesterol transport system is activated which, probably, reflects the development of adaptation mechanisms of hypocholesterolemia. The second period can be considered as a transition stage from norm to pathology and is most likely, connected with atherogenesis induction. In the third period, in spite of relative stabilization of total cholesterol level clear signs of hyperbeta and hypoalpha dyslipoproteinemias are observed. PMID- 1413121 TI - [Localization and causes of lipid peroxidation disorders in the rat cerebral cortex in the early stages of hereditary retinal degeneration]. AB - It is established that previously observed increased rate of the induced lipid peroxidation in brain tissue of rats with hereditary retinal degeneration as compared with normal rats is due to the change of the rate of this process in the microsome cortex brain fraction and was not observed in the mitochondrial synaptosomal and nuclear fractions. The content of nonheme iron ions in microsome cortex brain fraction of the Campbell rats is decreased by 35% and of the Fe ion was in the reduced form as compared with the Wistar rats. The ratio of Fe2+/Fe3+ in this fraction of the Campbell rats will be 5.21; Wistar rats--0.51. The increase of the reduced form of the Fe ion may be a result of the increased rate of the glucose-6-phosphate dehydrogenase activity in cortex brain tissue of the Campbell rats. We accept change of the content and the forms of the Fe ions in the microsome cortex brain fraction as a cause of the increased rate of induced lipid peroxidation in brain of the Campbell rats. All the observed phenomena are manifested at the early stage of life and indicated that different metabolic disorders can be observed in the Campbell rats not only in the retina and eye pigment epithelium but also in the brain tissue. PMID- 1413122 TI - [Incorporation of [3H]alpha-tocopherol into isolated nuclei and its binding by rat liver chromatin]. AB - The investigation of inclusion of [3H]alpha-tocopherol to isolated rat liver nuclei has revealed its nonspecific character. The presence of cytosol is necessary for specific interaction of alpha-tocopherol with nuclei. After the centrifugation of preliminarily labeled chromatin the most quantity of tocopherol was bound with oligonucleosomes and pelleted chromatin. It is supposed, that the preservation of supernucleosomes level of chromatin folding was necessary for the interaction of alpha-tocopherol with chromatin. PMID- 1413123 TI - [Role of alpha-tocopherol and retinol in the antiradical protection of the body in peptic ulcer]. AB - Retinol and tocopherol content, the intensity of spontaneous chemiluminescence as well as concentration of malonic dialdehyde in the blood of practically healthy persons of different age groups and in patients with gastric and duodenal ulcer have been studied. Results are presented. The lower content of tocopherol was revealed in the young persons as compared with other age groups, while the level of vitamin A was not established to depend on age. The content of tocopherol is established to decrease in the blood serum under peptic ulcer. Under these conditions low level of retinol correlates with considerable growth of spontaneous chemiluminescence. Reserve interrelation of tocopherol content in the blood with the level of spontaneous chemiluminescence as well as the absence of true dependence on the concentration of malonic dialdehyde at peptic ulcer are proved. Mechanisms of participation of vitamins E and A in the inhibition of free radical reactions are discussed, role of their deficiency in pathogenesis fo peptic ulcer is substantiated. PMID- 1413124 TI - [Oxygen binding of myoglobins of diving animals]. AB - When studying oxygen binding by myoglobins of diving animals it is shown that half-saturation of myoglobins obtained from the muscles of animals who can stop the external respiration for a long period of time occurs at oxygen strength of 0.62-0.67 mm Hg. Such indices of oxygenation of respiratory hemoprotein of muscles are characteristic of most mammals. Temperature being decreased from 37 to 15 degrees C, myoglobin affinity to oxygen considerably increases. PMID- 1413127 TI - [Surgery of ulcer disease]. PMID- 1413125 TI - [Selective N-heterylazimine inhibition of reactions catalyzed by rat liver glutathione transferase]. AB - Three reactions (nucleophile substitution, thiolysis and N-deoxygenation) catalyzed by rat liver glutathione transferase have been studied using several N heterylazimine inhibitors. The inhibitors are sharply different in their effectiveness in the transferase reactions. Their efficiency depends on their structure. The mechanism which underlies the found regularities is suggested. PMID- 1413126 TI - [Kinetic characteristics of Ca2+-phospholipid-dependent protein kinase from the rat liver in the early stages after x-ray irradiation]. AB - The changes of kinetic characteristics (apparent Km and Vmax) of the Ca2+ phospholipid-dependent protein kinase (protein kinase C) from the rat liver for substrates ATP and histone Hl 2 and 24 hours after total X-ray irradiation have been established. The obtained results evidence for the important role of these changes in early radiosensitivity of protein kinase C. PMID- 1413128 TI - [Chronic inflammatory bowel disease--current status]. AB - Chronic inflammatory bowel disease (IBD) encompasses the disease entities, ulcerative colitis (UC) and Crohn's disease (CD). An aetiologic agent has not yet been defined and the diagnosis is based, therefore, on the sum of clinical, paraclinical, radiologic, endoscopic and histopathologic features. In recent years pathogenetic studies have focused on immune mechanisms, transmissible infectious agents, the potential role of the normal intestinal flora, dietary factors, enzymatic alterations and genetic features, in addition to vascular, neuromotor, allergic and psychologic factors. The prevalence of IBD is increased in first-degree relatives of patients and there is a high rate of disease concordance among monozygotic twins. Thus abnormal genes may encode for one or several immunoregulatory factors, while bacterial wall products seem to activate colonic inflammatory cells in a non-specific way, leading to increased production of cytokines, complement-derived peptides, eicosanoids, platelet activating factor, biogenic amines, kinins, chemotactic oligopeptides, and neuropeptides. The named soluble inflammatory mediators, in addition to free oxygen radicals, are considered responsible for the secondary amplification of the inflammatory process. The corner stones in medical therapy of IBD are still corticosteroids and sulphasalazine (SAZ). The new oral salicylates, which are analogues of SAZ or "slow release" preparations of 5-aminosalicylic acid (mesalazine), have provided a therapeutic progress, because they are tolerated better than SAZ. Immunosuppressive agents, such as azathioprine and 6-mercaptopurine, reduce the requirement for corticosteroids and are effective in refractory CD, but the effect is delayed up to several months. The therapeutic action of cyclosporine A is not sustained, but often associated with side effects. Metronidazole has a beneficial effect on perineal disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413129 TI - [Phlebography as the "golden standard" in studies on prevention of thrombosis? A study on interobserver variation in a multicenter study]. PMID- 1413130 TI - [Autoimmune hepatitis. Forms of manifestation, diagnosis and treatment]. AB - A retrospective study concerning ten patients with autoimmune hepatitis (AiH), diagnosed during a 2 1/2-year period is presented. The age of the patients ranged from 25 to 82 years and nine of the patients were women. Their symptoms included jaundice, pruritus, fever, anorexia and fatigue during a few weeks to years. Seven patients had increased serum aspartate aminotransferase (ASAT) levels. The three patients with normal ASAT levels had hypoalbuminaemia, decreased level of prothrombin or high levels of serum immunoglobulin G. Moderate or high levels of smooth muscle antibody titer were detected in nine patients, while none had increased levels of anti-nuclear antibody titer. Histological features of moderate or severe chronic active hepatitis were demonstrated in nine patients. One patient presented with clinical and histological features of acute hepatitis. Prednisolone therapy was followed by biochemical improvement in all the patients. In one patient, maintenance therapy with prednisolone was combined with azathioprine. PMID- 1413132 TI - [Monosymptomatic pneumoperitoneum is not an indication for surgery]. AB - Pneumoperitoneum results from a perforation of the gastrointestinal tract in the majority of instances and the necessity for surgery is involved. In some cases with monosymptomatic pneumoperitoneum, surgery is unnecessary. A case of a man aged 64 with great amount of free intraperitoneal air is presented. The patient was clinically unaffected and had neither fever nor signs of peritoneal affection. The intraperitoneal air decreased slowly and disappeared after about 60 days. A self-sealing perforation of a duodenal ulcer was the cause of pneumoperitoneum. The most common causes of non-surgical pneumoperitoneum (PP) are discussed. IN CONCLUSION: Monosymptomatic PP is not an indication for emergency surgery. If the patient has no signs of peritoneal reactions conservative treatment can be considered. PMID- 1413131 TI - [Patients' knowledge about their own medication--does verbal information help? A blind, randomized study]. AB - Patient's knowledge about their own medicine is often insufficient, and this is possibly a contributory factor for noncompliance. We interviewed 65 patients (median age 61 years) from an out-patient clinic with free access and 86 patients (median age 68 years) from a hospital outpatient clinic. In both groups, knowledge about the dosage and the adverse effects of the drugs was poor. Old age and polypharmacy were associated with poor knowledge; there were no differences as regards knowledge between the two out-patient clinics. The 86 patients from the hospitals out-patient clinic were randomised to either 30 minutes of extended verbal information or to the standard information of the department. At the subsequent visit eight weeks later, a repeated interview indicated, that the informed group had generally improved knowledge about their own medication, while this was not the case in the control group. A statistically significant difference between the groups was, however, only found for medication knowledge about side effects. It is concluded that out-patients knowledge about their own medication is often poor, but can be improved by verbal information. PMID- 1413133 TI - [Spontaneous esophageal rupture during the 3rd trimester]. AB - A 30-year-old woman, 35 weeks pregnant, developed spontaneous rupture of the oesophagus following severe vomiting, probably caused by treatment with Ritodrin (Utopar). The symptoms, diagnosis and treatment of spontaneous oesophageal rupture are discussed. PMID- 1413134 TI - [CT in preoperative evaluation of renal tumors]. PMID- 1413135 TI - [Should we eat fish oil?]. PMID- 1413136 TI - [Should I also eat fish oils? A critical assessment of the use of fish oils in the prevention of ischemic heart disease]. AB - The effect of a daily dietary supplement of 6 g fish oil (3.4 g eicosapentaenoic and docosahexaenoic acid) on body weight, blood pressure, bleeding time and blood lipids was assessed in an open trial. The fish oil was taken for four weeks by nine 30-55 year-old individuals. An age- and sex-matched control group took equivalent amounts of safflower oil, which has an overall fatty acid composition similar to the tested fish oil. The fish oil supplement caused significant changes in body weight (median: +0.9 kg), systolic blood pressure (-10 mmHg), diastolic blood pressure (-5 mmHg), and high density lipoprotein (HDL) cholesterol concentration (+0.21 mmol/l), whereas serum triglycerides decreased insignificantly (-0.25 mmol/l). Low density lipoprotein (LDL) concentration were not affected. We observed no changes in the control group. In the discussion, it is underlined that fish oil supplementation may affect some risk markers of ischemic heart disease favourably. However, other important risk markers, including LDL cholesterol, are unaffected or unfavourably affected by fish oils. A more uni-directional reduction in risk can be attained by a change in dietary habits, which should be preferable to a fish oil supplement in the general population. Individuals who show critically low HDL/total cholesterol ratios, who are hypertriglyceridemic, or are mildly hypertensive may, however, benefit from a fish oil supplement of the amount tested here. PMID- 1413137 TI - [Use of pneumatic anti-shock equipment (MAST = military anti-shock trousers) in prehospital emergency treatment. A review]. AB - Employment of pneumatic anti-shock (MAST) equipment is a therapeutic possibility in some countries for hypovolaemic and shocked patients. This treatment may be associated with particularly serious side effects and no documentation is available to prove that MAST is beneficial for the patients. The only meticulous clinically controlled investigation concludes that MAST is without effect in city regions with well-trained paramedical or medical staff and employment of MAST can thus not be recommended. The effect of MAST outside urban regions is unknown and should be assessed by means of a clinically controlled investigation. PMID- 1413138 TI - [Dynamic continuous vectorcardiography]. AB - Continuous dynamic vectorcardiography is an ideal method for monitoring patients with myocardial ischemia. The monitoring is a non-invasive and real time registration and simultaneously safe and reproducible. The method has proved valuable for describing the evolution in different ischemic heart diseases. The method measures the electric myocardial activity in three orthogonal leads and a computer calculates the different vectorcardiographic parameters for the ST- and QRS-complexes. Vectorcardiographic registration is feasible for computer analysis, because it can summarize all information in a few parameters. Using continuous registration, the different parameters can show dynamic evolution and, in this way, describe the variability during acute myocardial infarction and unstable angina pectoris. The method also made it possible to evaluate anti ischemic treatment in patients, as for example thrombolytic therapy. PMID- 1413139 TI - [Sick-leave during pregnancy--focusing on textile workers]. AB - In order to illustrate the conditions involved in sick-leave during pregnancy, 593 consecutive parturient women received a questionnaire on the day after delivery. 48% of the pregnant women were certified as sick and 16% were admitted to hospital during pregnancy. The most common reasons for sick-leave were threatening abortion (19%), haemorrhage (18%) and threatening premature delivery (15%). The duration of sick-leave averaged 15 weeks as compared with 7.3 weeks in Denmark as a whole. In the subgroup of textile workers, 71% considered that the work was physically stressing and 70% were certified sick. Compared with all of the other occupationally active women, textile workers were more frequently certified sick, considered that their work was more physically stressing and had more frequently required sick-leave but were more rarely admitted to hospital. Similarly, textile workers had a greater risk for sick-leave on account of threatening abortion, pelvic loosening or pain in the locomotor system. PMID- 1413141 TI - [Cholesteatoma behind an intact ear drum--an overlooked disease?]. AB - On the background of increasing international interest for early diagnosis, pathogenesis and treatment of cholesteatoma in children, a sub-group is described and termed primary cholesteatoma, congenital cholesteatoma in the middle ear or cholesteatoma in the middle ear behind an intact ear-drum. This review is based on a retrospective review of cholesteatoma in children submitted to operation in Hjorring Hospital during a period of five years from 1986 to 1991. All of the children were under the age of 16 years. Out of 22 cholesteatoma treated operatively in children, the authors found six cases (27%) of congenital cholesteatoma. The symptomless congenital cholesteatoma in the middle ear is recognized clinically by otoscopy where it appears as a white shadow, most frequently in the anterior upper quadrant, behind an intact ear-drum. Early diagnosis is important and may be established by general practitioners, paediatricians and otologists at routine otoscopy. PMID- 1413140 TI - [Experiences with microcomputer based registration of esophago-gastro duodenoscopy]. AB - The development of and the experience with a microcomputer based register of endoscopy is described. The paper work was reduced from nine forms to one. The register provides the information necessary for budgeting the resources for staff and new equipment. The system provides the opportunity for analysing existing and new principles for treatment and provides information about the pattern of diagnoses, thereby supporting the running of clinical controlled studies. During the first 29 months, data from 6,014 endoscopies were collected. The categories of patients and the distribution of diagnoses is presented. PMID- 1413142 TI - [Extraintestinal manifestations of Salmonella infections illustrated by 2 cases of mycotic aortic aneurysm]. AB - Following an increased number of cases of Salmonella bacteraemia during recent years, an increased number of extra-intestinal manifestations were observed. Early diagnosis and rapid institution of treatment (both surgical and antibiotic) is decisive for the prognosis. Peroperative antibiotic treatment should cover possible Salmonella infection. PMID- 1413143 TI - [Conservative treatment of brain abscess complicating neonatal Escherichia coli meningitis]. AB - The case of a newborn infant who developed meningitis caused by E. coli is presented. During i.v. treatment with ampicillin and gentamycin in recommended doses and according to susceptibility patterns, the patient developed cerebral abscesses detected on CT. After changing to third generation cephalosporin, the patient improved clinically and the CT-changes regressed and disappeared. Because of their superior bactericidal effect, we recommend a third generation cephalosporin as a first choice in the treatment of neonatal E. coli meningitis. PMID- 1413144 TI - [The fat canard of Christmas]. PMID- 1413145 TI - [Obesity research has a reliability problem]. PMID- 1413146 TI - [Treatment of hypertension in the elderly]. PMID- 1413147 TI - [Treatment of isolated systolic hypertension in the elderly by general practitioners]. AB - By means of a questionnaire investigation, 150 general practitioners selected at random were asked about how they defined isolated systolic hypertension in elderly individuals, whether they employed medicinal treatment of this patients group and what their reasons for this were. The mean values for the highest systolic blood pressure which were considered to be normal were 175, 185 and 200 mmHg for the age groups 60-69 years, 70-79 years and > or = 80 years. Only approximately one fourth of Danish general practitioners consider medicinal treatment of isolated systolic hypertension and only at a much higher systolic blood pressure level than shown by a corresponding investigation among American doctors where 89% employ treatment for isolated systolic hypertension. On the basis of the present strategy in Denmark and the recent results from the first prospective placebo-controlled investigation of the treatment of isolated systolic hypertension, the future therapeutic strategy is discussed. PMID- 1413148 TI - [Reduction of blood pressure in children after physical training. The Odense study of school children]. PMID- 1413149 TI - [Temporal lobe epilepsy--psychiatric aspects and surgical treatment]. AB - The prevalences and types of psychiatric disorders connected with temporal lobe epilepsy and surgical treatment hereof are discussed. Studies comparing psychiatric morbidity among surgically treated patients and less selected groups of patients with epilepsy, respectively, are desired. Previous follow-up studies of patients undergoing temporal lobe resection point to a high prevalence of psychiatric disorders pre- and postoperatively, in terms of personality disturbances (especially aggression) and various psychotic disorders. On the basis of older studies, postoperative psychoses are believed to appear in 7-10% of surgically treated patients. New Brain Imaging and neurophysiological techniques permit a more precise focal diagnosis. Thus more selective surgical procedures have been introduced, e.g. resection of the amygdala and hippocampus. Together with an increased awareness of the importance of psycho-social factors and the absence of severe psychiatric disturbances for a good postoperative outcome this means that results of older studies may no longer apply. Studies reflecting present day conditions are needed. PMID- 1413150 TI - [Psychosocial consequences and surgical treatment of epilepsy. A review]. AB - Epilepsy is one the commonest neurological diseases. In 25% of the cases, particularly in patients with temporal foci, the seizures prove to be resistant to medicinal treatment. Several investigations have stressed that these patients have pronounced psychosocial problems which may be more important to the patient than the actual seizures. Taking into consideration the WHO definition of health as complete physical, mental and social well-being, patients with epilepsy have problems in all of these dimensions. The major problems are social isolation and employment. Surgical treatment of epilepsy has a pronounced effect on the seizures in 90% of the operations in the best series but it is still uncertain whether reduction in the number of seizures also implies better quality of life. The present data suggest improvement in the psychosocial conditions of the patients who functioned best preoperatively and who became seizure-free after operation. The importance of further longitudinal studies emphasizing the psychosocial aspects is stressed. PMID- 1413151 TI - [What do they do? And what can they do? Functional assessment of 70-year old subjects]. PMID- 1413152 TI - [Extent of HIV infection and AIDS among drug addicts]. AB - The purpose of this study was to review the extent of the HIV-epidemic and to make a prognosis about the number of AIDS-cases among drug addicts in the community of Copenhagen. In the public institutions for treatment of drug addicts, 191 HIV-positive individuals were known by January 1991. In the period August 1990-November 1991, 33 newly recognized cases of seropositivity were registered among drug addicts in the area of Copenhagen, but the time of infection was unknown. By October 1991, 53 cases of AIDS among drug addicts in Denmark were recorded. Based upon the knowledge of incubation period and mortality of AIDS, it was possible to set up a mathematical model, from which the number of expected AIDS-cases could be estimated. This model showed that the number of living drug addicts with AIDS in the community of Copenhagen probably not will exceed 20 during the coming years. It was also showed, that the number of drug addicts, who were infected with HIV in the primary spread of the virus in 1985-1986, was probably lower than 250. The actual prevalence and incidence of HIV-infection among drug addicts is uncertain, and there is a need for better surveillance of the epidemic. PMID- 1413153 TI - [Blood pressure check-up--routine blood pressure measurements in a patient with arteriovenous shunt and under dialysis]. AB - A case of untreated hypertension in a patient, where blood pressure could be measured in the right arm only is presented. At autopsy, the brachio-cephalic artery was found to be occluded explaining why blood pressure values were low. Significant left ventricular hypertrophy indicating high central blood pressure was found. Sudden death followed a spontaneous intracerebral bleeding. The value of conventional blood pressure measurement in patients with arteriovenous shunt because of chronic dialysis is discussed. PMID- 1413154 TI - [Psoriasis and anticoagulant therapy]. PMID- 1413155 TI - [Treatment of isolated systolic hypertension in the elderly]. PMID- 1413157 TI - [Antibiotic prevention in lung surgery]. PMID- 1413156 TI - [Intermittent claudication]. PMID- 1413158 TI - [Functional hypoglycemia. Fancy or fact?]. AB - Idiopathic reactive or functional hypoglycemia is not a recognised disease entity. It is defined solely on the basis of a history of hypoglycemic symptoms in everyday life, which can be relieved by food intake. However, the general opinion is that functional hypoglycemia exists, but it is not a frequent condition. The coincidence of a low blood glucose nadir and hypoglycemic symptoms in the hypoglycemic phase of the oral glucose tolerance test is not diagnostic of functional hypoglycemia. Endocrine dysfunction has never been demonstrated. The logical approach to the problem is to study blood glucose values during everyday life and at the onset of symptoms. This has been done in two controlled studies using reliable monitoring techniques. Low blood glucose concentrations during attacks could only be demonstrated in one of the studies and only in some of the subjects. Furthermore, the pattern of recorded symptoms was independent of the measured levels. Thus, these patients are probably not hypoglycemic in the true sense of the word. In a recent controlled but unblinded study, a higher blood glucose threshold for the onset of hypoglycemic symptoms was demonstrated in a group of patients with functional hypoglycemia. This, combined with a highly refined diet poor in fibre and starch, could provide symptomatic oscillations of blood glucose levels. However, much more research is needed in this field, before any conclusions are drawn. PMID- 1413159 TI - [Should all women be ordered gynecological examination a few days after delivery?]. AB - The results of a national survey, including all maternity units in Denmark, showed that 43 of 57 units (almost 75%) advocated routine pelvic examination a few days after delivery. Three out of 60 units did not answer the enquete corresponding to a 95% reply rate. Following the same procedure as the main part of delivery units in Denmark, all women confined in Sonderborg Hospital were offered routine pelvic examination four days after birth, however six days after caesarean section. A retrospective survey of the records for all women hospitalised for delivery in Sonderborg Hospital during 16.5.1990-16.11.1990 showed that 550 out of 715 women (77.0%) had been submitted to routine pelvic examination. Twenty one of these (3.8%) were treated according to one of the following abnormalities: atony of the uterus (14), superficial inflammation in caesarean scar of episiotomy (4) or endometritis (3). Based on a critical review of the cases, its concluded that all the treated complications were either insignificant, were treated unnecessarily or should have been diagnosed from the symptoms. As an alternative it is proposed, that routine pelvic examination a few days after birth should be restricted to selected women at risk. Other puerperal women should be observed closely and, depending on relevant symptoms, a pelvic examination should be made. In all cases and according to regulatives of the Danish Health Authorities (Sundhedsstyrelsen) all puerperal women should be offered a final examination by their practitioner eight weeks after birth. PMID- 1413160 TI - [CO2 laser treatment of proximal pharyngo-esophageal diverticula (Zenker's diverticula)]. AB - The pharyngo-esophageal diverticulum (Zenker's diverticulum) has traditionally been treated operatively by an external approach. Since the 1950's the endoscopic technique has been performed increasingly as a good alternative. Since 1989, we have treated Zenker's diverticulum endoscopically as a standard procedure, and hereby we present our results here. We use the Benjamin-Hollinger diverticuloscope, through which the septum between the diverticulum and esophagus is divided by a CO2-laser. Nine patients have been treated, five men and four women. Mean age 77 years (range 59-93). Diverticulum size varied between 1x2 cm and 6x6.5 cm. No major complications occurred. One patient had recurrence of symptoms after three months and was reoperated with the same technique. The mean observation period is 12 months (range 4-28). We find the endoscopic CO2-laser technique safe, and for the elderly age group suffering from Zenker's diverticulum, less traumatic than the external approach. PMID- 1413161 TI - [Preventive hepatitis B vaccination of hospital staff]. AB - In March 1990, a vaccination campaign against hepatitis B was organized in a municipal hospital in Copenhagen (Bispebjerg Hospital). The hospital staff (830 subjects) at risk of infection with hepatitis B were offered vaccination with Engerix B. The vaccination was given as Engerix B (recombinant DNA vaccine) in muscle deltoid after 0, 1 and 6 months. Antibody level was measured after one month. A total of 362 (44%) received vaccination against hepatitis B and 86% of these completed the vaccination schedule and received at least three vaccinations. 95% of the vaccinated subjects were protected after three vaccinations (HBsAg more than 10 IU/l). CONCLUSION: The recombinant DNA vaccine does not differ from the plasma-derived vaccine concerning immunogenicity and adverse reactions. There was a low compliance with the vaccination campaign, especially among doctors (35%) and laboratory technicians (35%), despite central organization. PMID- 1413162 TI - [Use of narcotics by school children in Greenland. A nation-wide study of habits of school children concerning narcotics]. AB - An attempt was made to describe the extent to which school pupils employ the intoxicants: tobacco, alcohol, hash and sniffing. The prophylactic committee, PAARISA, issues informative campaigns about intoxicants, the effects of which are assessed by means of investigations such as this. An anonymous questionnaire was employed. This was sent to 18 towns and seven villages distributed over all of Greenland. The questionnaire contained questions about social background, smoking habits, alcohol habits, sniffing and smoking of marihuana. The questionnaire was completed by the pupils in the schools under confidential conditions and was then returned to the author. The investigation was carried out during the period from 15.10. 1990- 15.11. 1990. All of the towns and the largest villages in all Greenland participated. The investigation was established on the initiative of the author in cooperation with PAARISA. A total of 1,934 school pupils aged from 12 to 19 years replied to the questionnaire. The percentage of replies was 88 of these questioned. Out of 1,557 pupils who spoke Greenlandic, 774 were boys and 783 girls. Out of 377 pupils who spoke Danish, 208 were boys and 169 girls. 26% of the Danish-speaking boys and 45% of the Greenlandic-speaking boys smoke, while 39% of the Danish-speaking girls and 61% of the Greenlandic-speaking girls smoke. Three quarters of the oldest age group smoke. Girls smoke more frequently than boys. 71% smoke more than three cigarettes daily. 87% of the Danish-speaking and 63% of the Greenlandic-speaking pupils had tried drinking alcohol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413163 TI - [Written patient information. Analysis of Danish biomedical research programs]. AB - All patients involved in biomedical research must, according to the Helsinki II declaration, receive complete verbal and written information about the project. Valid consent must be based on adequate information. This study analyses all of the 225 written patient information sheets submitted for approval to the regional research ethical committee covering the three southernmost counties in Jutland (Denmark) during the years 1989 and 1990. Linguistic analysis shows that the information is written in a difficult style with a median readability index of 48.2. It is generally recommended that information directed to the general public should have a readability index below 40 (approximately the level of the popular press). Analysis of information content shows that several important pieces of information are often missing: for instance, information about the name of the leader of the research and about the fact that the relationship with the institution will not be adversely affected by a refusal to participate in the research programme. PMID- 1413164 TI - [Total uterine rupture of a cesarean section scar during attempted vaginal delivery under epidural analgesia]. AB - A case of complete uterine rupture and abruptio placentae during an attempt of vaginal delivery under epidural analgesia in a woman with previous caesarean section is described and discussed. When using epidural analgesia for such a patient during vaginal delivery it is imperative that newly developed pain should be ascribed to the uterine scar and the diagnosis of threatening uterine rupture be made immediately. PMID- 1413165 TI - [Meningitis caused by Capnocytophaga carnimorsus with development of erythema nodosum]. AB - A case of meningitis in a 42-year-old previously healthy man caused by the gram negative rod Capnocytophaga carnimorsus is presented. The patient had erythema nodosum. Bacteremia was possibly induced during dental treatment. PMID- 1413166 TI - [Leptospirosis. A disease with non-specific initial symptoms]. AB - A case of leptospirosis in a young fish-farm worker is described. Early penicillin therapy was initiated solely on the clinical suspicion of the disease. The importance of recognition of the disease is emphasized together with early institution of penicillin therapy and effective eradication of vermin. PMID- 1413167 TI - [Fenoterol and asthma mortality]. PMID- 1413168 TI - [Insect allergy]. PMID- 1413169 TI - [Heart rate disorders in potassium and magnesium deficiency]. AB - Potassium and magnesium deficiencies are common in patients with heart disease. These are often coexistent and pathophysiologically related. Potassium deficiency cannot be treated without correction of concomitant magnesium deficiency. Correlations between serum levels and body stores are very poor for both ions. Therefore diagnosis and treatment of these conditions based on serum levels alone are erroneous. There is some evidence that it is primarily the intracellular depletion of these ions which is arrhythmogenic. Magnesium infusion has been proved effective in treatment of torsade de pointes ventricular tachycardia and arrhythmias induced by digoxin-intoxication, and is recommended in these conditions. Whether it is effective in other forms of arrhythmia is not yet elucidated. PMID- 1413170 TI - [Parasitic diseases in patients with impaired immune response. Clinical picture and diagnosis]. AB - Patients with impaired immune system are frequently infected with various parasitic diseases. The clinical picture is characterized by unusual manifestations and frequently severe recurrences of infections which are not normally serious. Some almost parasitic microorganisms produce symptoms exclusively in patients with impaired immune system. Parasitic infections have become increasingly common with the increasing number of patients who live for prolonged periods with impaired immune systems, often as a result of infection with HIV. Among the numerous parasitic infections which are observed in man, there are a few which occur particularly frequently in patients with impaired immune systems. This is a brief review of the clinical pictures and diagnostic options in parasitic disease in individuals with impaired immune system with particular emphasis on infections caused by: Pneumocystis carinii, Toxoplasma gondii, Cryptosporidium ssp., Microspora, Entamoeba histolytica, Leishmania ssp., and Strongyloides stercoralis. In patients with impaired immunity, parasitic infections frequently cause nonspecific symptoms and, on account of the impaired immunity, antibodies to the parasite are not always produced. The diagnosis of these infections is, therefore, based on morphological demonstration of the microorganism concerned, culture, specific antigen or DNA defections. PMID- 1413171 TI - [Prognosis and risk factors in acute dialysis-requiring renal failure after open heart surgery]. PMID- 1413172 TI - [Is it possible to change long-term benzodiazepine consumption by counseling in general practice?]. AB - Twelve general practitioners in a community offered 576 long-term consumers of benzodiazepines interviews in order to discuss possible reduction in medication. A total of 175 accepted the offer. Consumption of benzodiazepines was registered in the local pharmacy before and after the intervention. The total average reduction occurred in 20% and a definite reduction in consumption of sedatives by 30-49 years in 60%. The consumption of benzodiazepines by patients aged over 70 year remained the same as before the intervention. PMID- 1413173 TI - [Characteristics of a group of long-term consumers of benzodiazepines who were offered interview with their general practitioner]. AB - In connection with a project aimed at reducing the consumption of benzodiazepines in the Municipality of Odder, an attempt was made to select the patients who would be motivated for accepting offers of interviews with the general practitioner to discuss possible reduction of the consumption of benzodiazepines. It did not prove possible to select the group of patients who would be motivated for this type of encounter in advance. A positive effect of the offer of interviews to discuss possible reduction in the use of benzodiazepines was observed. More than half of the patients had either discontinued or had reduced the consumption of benzodiazepines. PMID- 1413174 TI - [Adolescents' wishes to have children]. AB - During the period 1984-1986, an investigation concerning sexual behaviour, contraceptive methods and pregnancies was performed among Danes aged 16-20 years in Denmark. A random sample consisting of 286 women (respondent rate = 75.3) and 336 men (respondent rate = 79.6) was interviewed by the Institute of Social Research. During the same time interval, 140 women admitted for legal termination of pregnancy in the County of Funen (respondent rate = 73.6) replied to a corresponding questionnaire. Some results have been published previously (4-6). This paper present results concerning the number of children the adolescents wish to have in the future and the age at which they want to become parents. A remarkable correspondence in the replies was found. The majority, including the women admitted for termination of pregnancy, the non-pregnant women and the young men, want to have two to three children. The majority, however, would prefer to have children when they themselves were between 20 and 30 years of age. In all, 62.9% (n = 171) of the non-pregnant women and 54.5% (n = 181) of the men would choose or advise application for legal termination, in the case of pregnancy. The women admitted for termination of pregnancy were asked to give priority to ten preformulated attitudes and their importance for the choice made when applying for abortion. A total of 70.5% (n = 93) replied that the formulation "It is too early for me to have a child" was of great importance for their choice, while the financial situation, housing problems and the possibility of being a single mother had lower priorities. PMID- 1413176 TI - [Insect allergy and sudden unexpected death]. AB - A case of sudden unexpected death after an insect sting in a middle aged man known to be allergic to insect stings is presented. In connection with an allergic shock, many years before death occurred, he had been offered allergological investigation. If the directives in the consensus report on insect sting allergy, recently published by the Danish Association for Allergology had been followed, similar deaths and expensive visits to casualty departments could probably be reduced. PMID- 1413175 TI - [Duplication in a medical department of tests previously performed in a primary sector]. AB - The aim of this study was to evaluate whether an insufficient flow of information from the primary to the secondary sector was the cause of unnecessary duplications of investigations. From practitioners of 202 patients admitted to a medical department information about paraclinical examinations during the previous year was obtained. In all 111 general practitioners participated. An average of 3.0 blood analyses and 0.9 other investigations were carried out on each patient. 44% of the patients were not investigated at all. An average of 1.9 blood analyses and 0.2 other investigations on each patient were repeated. 22% of the repetitions in both cases were due to insufficient communication between the practitioner and the hospital. These figures seem low and insufficient communication between the primary and the secondary sector appears to be a minor problem. PMID- 1413177 TI - [Congenital tuberculosis. 2 case reports]. AB - Two cases of congenital tuberculosis are presented and the literature is reviewed. One child survived without sequelae while the other survived but was severely handicapped. The importance of early diagnosis and treatment of this rare but serious manifestation of tuberculosis is emphasized. PMID- 1413178 TI - [Experiences with breast cancer surgery performed in a specialist's practice]. PMID- 1413179 TI - [Follow-up after treatment of colorectal neoplasms]. PMID- 1413180 TI - [Check-ups of colorectal neoplasms--current practice]. AB - In order to investigate the practice for control of patients with colorectal adenomata and cancer, a questionnaire investigation was carried out in 1990-1991 among 53 Danish surgical departments. The investigation revealed great differences in the control programmes offered to these patients as regards the methods, the intensity and duration. In addition, differences were present in the control pattern for adenomata in specialist departments as compared with the remaining departments where there was a tendency to very frequent but, on the other hand, brief control. On the basis of these results, it is considered necessary that a reference programme should be prepared on this subject. PMID- 1413181 TI - [The pacemaker syndrome]. AB - The pacemaker syndrome is a complex of symptoms consisting of heart failure, near fainting, sensations of pulsation in the neck or abdomen or cough which develop or are aggravated after cardiac pacing. Objectively, a fall in systolic blood pressure is observed in the majority of cases and also canon waves in the neck veins, signs of heart failure, retrograde arterial activation and possibly canon a-awaves in the central venous pressure. The syndrome occurs in approximately 15% of the patients with ventricular pacing. The condition is most probably caused by lack of atrioventricular synchrony with resultant distension of the atria which results in a reflex mediated decrease or defective increase in the total peripheral resistance and, thus, a fall in systolic blood pressure. Treatment consists of establishing normal atrioventricular synchrony either by implantation of an atrial or AV-sequential pacemaker or by re-programming so that the patient has, primarily, his own rhythm. Ensuring normal atrioventricular synchrony has also other advantages as several investigations have shown that 60-80% of the patients prefer this form of pacing rather than ventricular pacing. The working capacity improves and the patients feel subjectively better and the risk for development of chronic atrial fibrillation and heart failure decreases. PMID- 1413182 TI - [Surgical treatment of temporomandibular joint ankylosis]. AB - Surgical treatment of temporo-mandibular joint (TMJ) ankylosis may be a particularly difficult procedure due to unfavourable anatomic configurations and the proximity of vital structures. Postoperatively, it is followed by an often long and painful period of physiotherapy. The results of treatment of eight patients with TMJ ankylosis are reported. Different methods were used according to age of the patient and the extent of the ankylotic changes. The importance of early treatment is emphasized. This results in less extensive surgery and reduces secondary growth anomalies of the jaws. PMID- 1413183 TI - [Effect of 0-(beta-hydroxyethyl)-rutoside (Venoruton) on symptomatic venous insufficiency in the lower limbs]. AB - Forty-three patients recruited from general practice with symptom-producing chronic venous insufficiency in the lower limbs participated in a randomized double-blind clinical trial with Venoruton (300 mg x 3) or a placebo for 28 days. Twenty-eight patients were treated with Venoruton and 19 with a placebo. None of the patients received other forms of treatment for chronic venous insufficiency. No differences were observed between the two groups as regards changes in symptoms (swelling, pain, heaviness, restlessness, itching and cramps) the subjective assessment of the discomfort in the extremities or the circumference of the limbs. Venoruton does not appear to have any effect on chronic venous insufficiency in the lower limbs. PMID- 1413184 TI - [Measurement of urethral stress relaxation in women]. PMID- 1413185 TI - [Failure of the pacemaker in electric cardioversion of atrial fibrillation]. AB - A 72-year-old man with an AAI-rate-responsive pacemaker (Siemens-Elema Sensolog III; unipolar pacing electrode) was admitted for cardioversion of atrial fibrillation. Electrical defibrillation was followed by severe nodal bradycardia and pacemaker malfunction characterized by loss of atrial capture. The pacemaker failure was due to an acute rise in the stimulation threshold, possibly secondary to current-induced tissue damage at the electrode-endomyocardial interface. It is recommended that a pacemaker is reprogrammed to maximum pulse voltage amplitude prior to elective DC-cardioversion and that serial measurements of the myocardial stimulation threshold are performed after defibrillation. Other factors essential for the management of the pacemaker patient who requires electrical defibrillation are outlined. PMID- 1413186 TI - [Diabetes and diet--changes in insulin resistance induced by food and need of individualized dietary guidelines]. PMID- 1413187 TI - [A model for standardizing of clinical physiological/nuclear medical results]. PMID- 1413188 TI - [Diabetes and diet--does the rationale hold even in the 1990's?]. PMID- 1413190 TI - [The Danish fund for basic research--a new cigar-box]. PMID- 1413189 TI - [Thoughts from a consensus conference]. PMID- 1413191 TI - [Stress fractures]. AB - The authors present stress fracture (fatigue fracture). Theories about the cause, the underlying mechanism, etiology, pathology, localisation, diagnoses and treatment are discussed, and two case histories are mentioned. Suitable precautions are recommended for runners. The authors would like to emphasize the importance of further investigations including technetium scintigraphic, in cases where stress fracture is suspected. PMID- 1413192 TI - [Malaria and pregnancy]. AB - In regions where malaria is endemism, the disease is a recognised cause of complications of pregnancy such as spontaneous abortion, premature delivery, intrauterine growth retardation and foetal death. Malaria is seldom seen in pregnant women in Denmark but, during the past two years, the authors have treated four patients in the University Hospital in Copenhagen. These pregnancies were all successful but two of the mothers required emergency Caesarean section on account of threatening intrauterine asphyxia. The patients came relatively late for treatment which may be because not only the patients but also their practitioners were unaware that malaria can occur several years after exposure. Three out of the four patients had employed malaria prophylaxis. As resistance to malarial prophylactics in current use is increasing steadily, chemoprophylaxis should be supplemented by mechanical protection against malaria and insect repellents. As a rule, malaria is treated with chloroquine. In cases of Falciparum malaria in whom chloroquine resistance is suspected, treatment with mefloquine may be employed although this should only be employed in cases of dire necessity in pregnant patients during the first trimester. Severe cases should be treated with infusion of quinine. During pregnancy, benign malaria may run a violent course and pregnant women with malaria should be monitored in maternity departments and should be treated in cooperation with specialists in tropical medicine. PMID- 1413193 TI - [Sensory deprivation]. AB - A review of sensory deprivation is presented. The history of the concept and the terminological problems are reviewed. The symptoms are subdivided into: perceptual, cognitive and affective and the physiological disturbances are reviewed. Various etiological theories are discussed. These include biological, psychodynamic and social psychological theories. Experimental variables related to the subject, the investigator and the design of the research are presented. A review of the clinical and practical implications of sensory deprivation is given. It is emphasized that sensory deprivation might contribute to development of symptomatology in numerous situations. Finally, the potential therapeutic effects of controlled sensory deprivation are discussed. PMID- 1413194 TI - [Medial acoustic neurinomas. A new clinical subsection of acoustic neurinomas]. PMID- 1413195 TI - [Product-related home accidents among children. A study of 1590 injuries]. PMID- 1413196 TI - [3-layer anastomoses after resection of colorectal cancer. A prospective study of 1015 anastomoses]. AB - This study included patients who underwent elective curative resection of adenocarcinoma of the large bowel with primary suture of the anastomosis. The overall incidence of clinical anastomotic leakage was 5%. The incidence of anastomotic leakage was significantly higher in men than in women after low anterior resection. The three-layer anastomosis has no advantage in large bowel surgery when compared with data from other sutured anastomoses reported in the literature. PMID- 1413197 TI - [Consumption of psilocybin-containing hallucinogenic mushrooms by young people]. AB - The aim of this questionnaire survey was to investigate the extent of hallucinogenic mushroom consumption among students from a high school in the county of Aarhus, Denmark and among students at the University of Aarhus and students from the Danish school of journalism in Aarhus, Denmark. 3% of the high school students had used psilocybine-containing mushrooms as a hallucinogen. Only 1% had experience with LSD. Of the students at the University of Aarhus, and students from the Danish school of journalism in Aarhus, 333 persons (83%) returned the anonymous questionnaire. 9% had experience with hallucinogenic psilocybine containing mushrooms while only 2% had LSD experience. The use of hallucinogenic mushrooms was surprisingly high. This suggest that mushrooms are the most commonly used hallucinogenic substance in Denmark and that the use has exceeded that of LSD. Compared to non-users mushrooms users had significant more friends with mushroom experience. Furthermore, the study shows that the intention to use mushroom is commoner in persons who have friends with HPS experience. We find that the use of mushroom takes place in minor groups known to each other. Compared to non-users, mushroom-users are significant more experienced with marijuana and other substances. Unfortunately, our data do not permit us to show whether mushroom users are more inclined to try other drugs or whether persons with a high drug experience use mushrooms as well. Further investigation on the subject is recommended. PMID- 1413198 TI - [Serum creatine kinase isoenzyme MB and myoglobin in patients with acute myocardial infarction and coronary reperfusion]. AB - Thrombolytic therapy in patients with acute myocardial infarction (AMI) changes the time-concentration curve of serum creatine kinase isoenzyme MB (CK-MB) and serum myoglobin. In this study, 60 AMI patients received thrombolytic therapy and acute coronary arteriography, or conservative treatment. Group one (n = 32) demonstrated a patent infarct-related artery after intravenous thrombolytic therapy; group two (n = 17) had an initially occluded coronary artery which became patent during catheterisation; group three (n = 11) did not receive thrombolytic therapy. Frequent serum CK-MB and myoglobin measurements showed that patients with acute coronary reperfusion had a rapid increase, an earlier peak value and less total release of both CK-MB and myoglobin to blood compared to AMI patients treated conservatively. The changes in serum myoglobin compared to CK-MB demonstrated an even more rapid, more uniform, and relatively greater increase. Measurements of serum myoglobin may be a useful non-invasive method for evaluation of thrombolytic therapy in AMI patients. PMID- 1413199 TI - [Intravagal paragangliomas]. AB - Two patients with vascular tumors adjacent to the carotid branch of the vagus nerve are presented. Contrary to expectations, the tumours proved to be intravagal paragangliomata. Both were treated surgically. PMID- 1413200 TI - [Atrial flutter with paroxysmal 1:1 atrioventricular conduction]. AB - Three patients with "lone" paroxysmal atrial flutter complicated by paroxysms of 1:1 AV conduction are presented. One patient (42 years of age) had been misdiagnosed as an neurotic for 18 years. The mechanism, diagnosis and treatment of the condition are outlined. The most characteristic symptoms are dizzy spells and fainting. The recommended diagnostic procedures include long term ECG recording by telemetry or Holter, exercise-ECG and oesophageal-ECG. PMID- 1413201 TI - [Venereal diseases in Greenland. Positive trends during the last 6 months]. PMID- 1413202 TI - [Neonatal mortality and Streptococcus agalactiae]. PMID- 1413203 TI - [Quality evaluation--counting and interpretation]. PMID- 1413204 TI - [Research in physiotherapy--rational physical medicine and physiourgy]. PMID- 1413205 TI - [Good will]. PMID- 1413206 TI - [Cerebral aneurysms in children. Etiological aspects]. PMID- 1413207 TI - ["Case manager" in district psychiatry. A review of the concept]. AB - During the past 20 years, the "case manager" has become a central expression in district psychiatry in USA. The case manager is a person who has the main responsibility for coordination and to a varying extent granting of the district psychiatric contributions to persons with prolonged psychoses. This function was introduced because the previous system with many administrative and physically separate offers appeared to be uncoordinated, mutually competitive and ineffective. The case manager acts as a supplementary "ego" for the patient on his own terms and has an active supportive function. Whereas, coordination was previously the central task, it became considered to an increasing extent more suitable that a multidisciplinary team of case managers supply the district psychiatric therapy themselves. Investigations reveal that the results are just as good or even better than those of the previous combination of hospitalization and outpatient treatment and that the patients are more satisfied. Many hospitalizations can be avoided but the employment of resources is probably not reduced on account of expenses for the case manager function and housing. The number of patients per case manager varies between four and 50, depending on the therapeutic needs of the patient group and, in particular, the tasks which the case manager must perform (all over the treatment or coordination of treatment administered by others). On account of the close contact by the case manager and his supportive activity, there are reasons for particular attention to ethical problems concerning personal choice and exchange of information. Utilization of the American experience with case managers is recommended simultaneously with avoidance of administrative practical splitting of district psychiatry which would make the total therapy ineffective. PMID- 1413208 TI - [Does peroperative monitoring with pulse oximetry reduce the occurrence of hypoxemia?]. PMID- 1413209 TI - [Pelvic inflammation after induced abortion]. AB - A total of 949 women referred for legal termination of pregnancy in the first trimester participated in an investigation to assess the risk of pelvic inflammation in connection with the intervention in women with and without previous pelvic inflammation in connection with previous pregnancies, the gestational age and the clinical experience of the surgeon. Women who had not borne children developed pelvic inflammation more frequently after legal termination of pregnancy (p < 0.01) than women who had previously borne children. Women with previous pelvic inflammation developed renewed pelvic inflammation, if they had not previously borne children (p < 0.01) or if they had previously undergone legal termination of pregnancy (p < 0.05). Women without previous pelvic inflammation developed pelvic inflammation significantly more frequently, if they had not previously been pregnant (p < 0.05). The occurrence of pelvic inflammation was independent of the gestational age and the clinical experience of the surgeon. PMID- 1413210 TI - [Registration under the diagnosis of traumatic hip luxation in the national registry]. AB - A national study of patients treated on account of traumatic dislocation of the hip in Denmark in 1989 and 1990 revealed that 755 cases had been registered under this diagnosis in the National Patient Register. A review of case reports from 71 departments with 755 registered identity numbers in the National Patient Register demonstrated that 121 patients had been treated for traumatic dislocation of the hip during the same period, and that seven of these had not been registered via the National Patient Register. The remaining 605 patients (80%) had either sustained dislocation of a hip prosthesis or had congenital dislocation of the hip. It is concluded that the Danish National Register, in its present form is of no value whatsoever in registration of traumatic dislocation of the hip nor congenital dislocation of the hip or dislocation of a total hip prosthesis. PMID- 1413211 TI - [Exercise echocardiography. A new valuable method for demonstration or exclusion of myocardial ischemia]. AB - The aim of our study was to assess the diagnostic value of exercise echocardiography compared with exercise ECG and coronary arteriography. Exercise echocardiography was performed in 60 consecutive patients referred for coronary arteriography because of suspected coronary artery disease. Echocardiography was carried out in combination with bicycle exercise ECG and was performed 1) at rest before exercise with the patient supine, 2) at peak exercise on the bicycle and 3) immediately after exercise in supine position. Conventional standard views were recorded by means of an image computer. For the regional wall motion analysis, images were displayed simultaneously from the rest, peak and post exercise situations in a quadscreen format. Ischemia was diagnosed when wall motion deteriorated from rest to peak or post exercise in at least one out of a total of 16 left ventricular segments. Analysis was made without knowledge of patient data or results of exercise ECG or coronary arteriography. No patient was excluded because of reduced echocardiographic image quality during exercise or other technical reason. Coronary arteriography was performed in all patients and used as reference. The sensitivity of exercise echocardiography was 91% and the specificity 100%. The predictive value of a positive test was 100% and the predictive value of a negative test 78%. For exercise ECG the corresponding values were 58%, 100%, 100% and 39% respectively. We conclude that exercise echocardiography seems to be useful for the diagnosis and exclusion of ischemic heart disease. This and other studies indicate that the method is more sensitive than exercise ECG. PMID- 1413212 TI - [Amphetamine abuse in Denmark]. AB - Over a five-year period (1985-1989) among a population of 5 million, a survey was made of the presence of amphetamine in 741 cases, in living persons where the police had asked for analyses for amphetamine(s), narcotics, heroin-like compounds, methadone etc. Cases, where the requisition was for morphine (heroin) only, were not included, on account of analytical reasons. Two hundred and fifty nine cases were found to be positive for amphetamine, with only 18 cases in 1985 followed by approximately 60 cases per year during the remainder of the period. Most of the cases concerned men (93%). The age range was 15-58 years with a median of 26 years. In 194 of the amphetamine-positive cases where relevant information was available, 56% were cases of violation of the traffic laws, 17% were cases of violence, 3% were cases of sexual offence and 9% were cases of robbery. Nineteen of the 259 amphetamine-positive cases were analysed only for amphetamine and, in 75 cases, only amphetamine was found. In the 165 remaining cases, there were 279 positive findings of other drugs/narcotics than amphetamine with benzodiazepines, morphine, cannabis and methadone as the main groups with 86, 57, 49 and 44 findings respectively. PMID- 1413213 TI - [Emergency services in the admission department of a central hospital]. AB - Medical treatment during the evening and night hours has been the subject of debate at present on account of changes in the practitioner-on-call system. The emergency medical service in the catchment region for the Central Hospital in Naestved before these changes was therefore analysed. Services rendered in this region outside working hours, both by the physician-on-call and the hospital, were registered for the period 1.12.1989-31.1.1990. A total of 8,742 consultations occurred during the period, viz every tenth member of the population sought medical advice. The majority of these contacts were with the practitioner-on-call as 7,253 (83%) sought their general practitioner first and the remainder came to hospital. This corresponds to 117 consultations with the practitioner-on-call and 22 visits to the casualty department per 24 hours of emergency service. Among the patients seeking help from the casualty department, it was found that 30% could have been treated in general practice. Among the taks for the practitioner-on-call, there were 27% telephone consultations, 21% in practice and 52% home visits. No differences were observed between urban rural regions as regards the proportions of services but the number of services followed population percentages. 11% sought medical help at night and 1/3 of these patients were referred to hospital. In the present material, there appeared to be relatively great misuse of the telephone number 000 (equivalent to 999) as only 1/3 of these patients were admitted to hospital. A total of 1,263 patients were admitted to hospital and 78% (982) of these had been seen primarily by the practitioner-on-call.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413214 TI - [Torsades de pointes ventricular tachycardia caused by terodiline (Mictrol)?]. AB - We report a 84 year old man taking terodiline who had torsades de pointes ventricular tachycardia with prolongation of the QT-interval. The QT-interval became normal after withdrawal of terodiline. Worldwide, the manufacturers have received a total of 37 reports of ventricular tachyarrhythmia during the past months, 28 of which were torsades de pointes ventricular tachycardia and have decided to recall the product temporarily. PMID- 1413215 TI - [Legionnaires' disease--a multifaceted syndrome]. AB - Multiorgan involvement is often seen in Legionella infections. We report two cases, with classical pneumonia complicated by facial paresis and severe kidney affection demanding haemodialysis. One patient had Legionella infection concomitantly with pneumococcal pneumonia. As the diagnosis often is not verified till weeks after onset of illness, it is concluded that the treatment should be started and maintained on clinical suspicion. Isolation of another respiratory pathogen does not exclude the possibility of Legionella infection. PMID- 1413216 TI - [Migration of suture material from the abdominal cicatrix to the urinary tract]. AB - Migration of foreign material to the genitourinary tract, often from the gastrointestinal tract through a fistula or perforation is well known. In this case, migration of a non-absorbable suture material from the abdominal wall to the urethra is illustrated. The possible mechanism was insufficient closure technique. PMID- 1413217 TI - ["Case manager" in district psychiatry--a Danish model]. PMID- 1413218 TI - [Risk of melanoma and health education campaign]. PMID- 1413219 TI - [Cutaneous malignant melanoma in Denmark]. PMID- 1413220 TI - [Microbiology and practice--we need each other]. PMID- 1413221 TI - [Clinical microbiological service in general practice in the municipality of Copenhagen. Experiences from the clinical microbiological department at the Hvidovre Hospital 1987-1991]. AB - Since 1987, the clinical microbiological department in Hvidovre Hospital has served physicians in primary health care in the municipality of Copenhagen with microbiological diagnoses and instruction. This paper describes the service model and experience gained during the past four years. During the observation period, the annual number of analyses doubled. In 1990, 66,460 analyses were performed for a total of 399 physicians. The number of specimens per physician varied from 1 to 1903 with a median value of 95. Chlamydia specimens (CS) and vaginal discharge specimens (VDS) examined for yeasts, Gardnerella and Trichomonas comprised the two largest categories. In spite of the increasing number of specimens, the overall rate of positive samples remained unchanged. Physicians who sent many CS in 1990 scored a significantly lower positive rate than physicians who sent few, however, no corresponding difference was demonstrable for VDS. Thus, there is scarcely evidence to assume that microbiological specimens are taken on less strict indications than previously. The increasing number of specimens reflects rather a hitherto uncovered need for microbiological diagnosis in primary health care. Specialists scored significantly lower positive rates for CS and VDS than general practitioners, which may indicate that these specimens are often repeated unnecessarily, when a patient is referred to a specialist. With a view to decentralizing selected categories of specimens, including VDS, courses in microscopy were held, in which one fourth of the physicians of the region participated. A questionnaire survey evaluating the course showed that there is a great interest among physicians in primary health care to perform simplified microbiological diagnosis, but there is still a great need for training and education. PMID- 1413223 TI - [Dog bites in the sledge-dog districts of Greenland]. AB - Serious attacks on humans by dogs occur every year in Greenland. As prophylactic measures, cutting of dogs canine teeth and chaining of sledge dogs have been compulsory for many years. The significance of cutting of canine teeth and municipal regulations concerning keeping the sledge dogs in Greenland was evaluated in a retrospective study of the death certificates and the nosocomial reports. A total of twenty-two dog bite-related fatalities from 1967 through 1989 and 23 hospitalized patients following dog attacks from 1986 through 1988 in a population of 15,000 inhabitants and 29,000 dogs was studied. In only two of the killed and four of the hospitalized persons, reports of intact canine teeth as demonstrated by the typical lesions were available. However, the severe cut-out wounds in 14 survivors and twenty fatalities with great loss of tissue indicated intact canine teeth of the dogs. Unchained dogs were most frequently involved, but at least four fatalities and one severely injured person were caused by chained dogs. 87% (39/45) of the victims were under ten years of age, so future intervention should primarily involve this group despite a declining mortality rate since the mid-seventies. Small children should be escorted by adults out-of doors and first aid education of laymen ought to have a higher priority because half of the killed children were still alive, on arrival in hospital. Infants and toddlers should be carried in an amaat, a special rucksack well known in the Eskimo culture and still used in Eskimo Canada, or alternatively rucksacks mounted on a tubular frame of aluminium. PMID- 1413222 TI - [Hyperthermic regional perfusion in malignant melanoma of an extremity]. AB - Circulatory isolation of an upper or lower limb and perfusion of this with heated cytostatics is an established method of treating local recurrence and in-transit metastases from malignant melanoma. Not only recurrence-free survival but also total survival are increased compared with the results after surgical excision alone. Even when this method is employed in connection with excision of a primary tumour, there appear to be favourable effects as regards recurrence-free and total survival of patients in high risk groups (tumour thickness > 1.5 mm and/or Clark level IV-V). The actual treatment is well tolerated by the patients and complications in the form of oedema of the limb and wound infection are reversible. The frequency of amputation is low and, similarly, the mortality which is 0.6%. As the frequency of malignant melanoma is increasing and, as a great proportion of the melanomata are localized to the extremities, these patients should be offered hyperthermic regional perfusion on removal of the primary tumour and also if recurrence occurs. PMID- 1413224 TI - [Efficiency of a screening program for gestational diabetes]. AB - From 1.1.1991-31.5.1989, we evaluated a selective screening system for detection of diabetes in pregnancy in an unselected consecutive population of 665 pregnant women. The screening procedure was carried out by the general practitioners and the midwives. The screening was based on clinical criteria for potential diabetes consisting of previous delivery of a large baby, a family history of diabetes and obesity combined with examination for glucosuria and determination of the fasting blood glucose concentration. Only 2% of the pregnant women were examined correctly and only two out of 665 women were found to have diabetes in pregnancy. The screening procedure failed when it was organised by general practitioners and midwives. PMID- 1413225 TI - [Screening for gestational diabetes in Denmark]. AB - A questionnaire regarding the screening procedure for gestational diabetes was sent to all maternity hospitals in Denmark in 1990. Only 15 out of 51 departments used the screening procedure as proposed by Guttorm & Pedersen. Glucosuria was a clinical risk factor in 49 of 51 departments. There was no agreement about the histories and clinical risk factors. The factors used were family history of diabetes, obesity, a previous infant weighing 9 lbs or more, a previous infant born with low gestational age, habitual abortion, previous perinatal deaths, previous preterm delivery, hydramnios, excessive fetal growth or glucosuria in the present pregnancy. No department used universal screening. PMID- 1413226 TI - [Loratadine in hay fever]. PMID- 1413227 TI - [A hypersensitive reaction after radiography of the colon]. AB - A case of systemic allergic reaction following barium enema is described. The reaction was most probably provoked by a latex balloon on the rectal catheter. PMID- 1413228 TI - [Malignant melanoma of the penis]. AB - Malignant melanoma of the penis is rare, and accounts for only a small percentage of penile carcinomas. The prognosis is poor, and most patients die within three years due to distant metastases. Awareness of the possibility of malignant melanoma occurring at this uncommon site is an important factor in early diagnosis and consequent improvement of survival. The case report of a man with malignant melanoma of the penis is presented. PMID- 1413229 TI - [Menopausal estrogen therapy and risk of breast cancer]. PMID- 1413230 TI - [Quality assurance or research?]. PMID- 1413231 TI - [Danish-Bagladesh Leprosy Mission]. PMID- 1413232 TI - [Possibilities and limitations in gerontology]. PMID- 1413233 TI - [Research of aging: epidemiological perspectives]. AB - The epidemiological aging research has the descriptive task of characterizing the phenomena of aging and their consequences: illness, disability, handicap, and death--in defined population groups and comparing these groups. The other closely related task is analytical epidemiology, which searches for predictive or causal factors: traits, events or conditions of the aging phenomena. Special problems for this research are created by the facts that exposure to the causal factors often may be assumed to have taken place long time before the aging process becomes apparent, that the causal factors may act on cumulative basis over long time, that the effects may be irreversible, and that the factors may no longer play a role at advanced age. The possible role of genetic factors, acting alone or in combination with environmental factors, must be considered and elucidated by special epidemiological methods. The rapid advances in molecular biology raise expectations about epidemiological utilization providing much more precise assessment of the genetic contribution to the aging phenomena, which also will improve the outlook of identification of environmental factors, particularly when there is a gene-environment interaction. The results of these studies will contribute to prevention and treatment of the health problems related to aging. PMID- 1413234 TI - [Research on aging: biological perspectives]. AB - Aging is a part of the continuous process from conception to death and is strongly modulated by environmental factors throughout the lifespan. Variability in functional capacity between different organs and between individuals therefore increases with aging. This review will discuss two tissues of importance for the fitness of the aging human being: connective tissue and bone. Connective tissues become stiffer with age, which can be mitigated by physical exercise. The physical-chemical stability of collagen is a precise measure for the functional age of the organism. While in the aged, the healing (formation of connective tissue scar) of uncomplicated incisional wounds is slightly impaired, the healing of ischemic wounds is endangered. The clinical observation that "simple" wounds also heal less well in the aged might be due to the presence of diseases with ischemia and other pathologies. During normal aging bone loses mass, structural continuity, and strength. When pronounced, these changes cause osteopenia and osteoporotic fractures. The age-adjusted incidence of osteoporotic fractures is increasing on account of changes in our lifestyle. Preventive efforts, with increased physical activity as the main feature, must be implemented to alter this trend. Our knowledge of the mechanisms of aging is not yet sufficient to formulate a policy containing preventive measures enabling man to achieve his maximum biological lifespan with good physical health and a high quality of life. Multidisciplinary efforts by biologists, clinicians and epidemiologists are warranted to achieve this goal. PMID- 1413235 TI - [Research on aging: geriatric perspectives]. AB - Geriatric efforts have prophylactic effects on further reduction of functional ability at every link in the therapeutic chain by means of interdisciplinary qualitative and quantitative assessment which establishes goal and plans which lead to coordinated action. This results in early diagnosis of multiple pathology, reduction of polypharmacy, confidence on account of good information, continuity on account of coordination between primary and secondary sectors, simultaneous efforts, early interruption of the cascade effect which results in production of helpless patients. By means of clinically controlled trials, effects have been obtained on a number of recently discovered diagnoses requiring treatment, unnecessary medication is withdrawn, conditions of rehabilitation, functional ability, quality of life, employment of bed-days, institutionalization and mortality. It is necessary to state that this is the only age group where the effect is obtained without further expense or where the effort has even resulted in economic savings. In Denmark, research is required as regards how prophylactic health visits to the elderly can best be carried out in all communities, the risk situations (death of a spouse, removal, illness) which require immediate increased efforts and research into how offensive geriatrics is to be established, how rehabilitation is ensured for healthy and sick elderly patients and research into the occurrence and treatment of the five geriatric giants (immobility, instability, incontinence, intellectual reduction and iatrogenesis). More Danish controlled trials are required of the individual components in and the total function of geriatric assessment and rehabilitation and the significance of personal choice when the functional ability is such that dependence on care by others is inevitable and, finally, the conduct and expenses of various arrangements. PMID- 1413236 TI - [Risk to the surgeon of trauma and exposure to blood during thoracic surgery]. PMID- 1413237 TI - [Organization of obstetric ultrasonography in Denmark in 1990]. PMID- 1413238 TI - [99mTc-HMPAO leukocyte scintigraphy in inflammatory intestinal disease]. AB - Eighteen patients, suspected of active inflammatory bowel disease, were investigated. The 99mTc-HMPAO-leucocyte scintigraphy was evaluated using the results of the simultaneous clinical examinations, which included clinical and biochemical parameters, small intestinal series, colonoscopy and, in two patients, operation, as reference. In agreement with the clinical examinations, the leucocyte scintigraphy indicated active inflammatory bowel disease in 14 of the 18 patients. The leucocyte scintigraphy disclosed inflammation in all of the 19 bowel segments, in which the clinical examinations indicated active inflammation. In three patients with Crohn's disease the scintigraphy indicated more extensive inflammation. A correlation between the scintigraphic activity and the Crohn's Disease Activity Index was found. However, the leucocyte scintigraphy did not seem useful as a disease activity index. The 99mTc-HMPAO-leucocyte scintigraphy seemed especially useful in severely ill patients and in patients suspected of relapse. PMID- 1413239 TI - [Encrusted ureteral endoprosthesis]. AB - The case of a patient with a ureter endoprosthesis is presented. The endoprosthesis became encrusted after remaining in position for three years. Ureter endoprosthesis in connection with renal or ureteric calculi should only remain in position for 6-8 weeks. PMID- 1413240 TI - [Captopril-induced toxic hepatitis]. AB - Captopril, the competitive inhibitor of angiotensin-converting enzyme, has proved efficient in the treatment of arterial hypertension and heart failure. Its use is generally associated with low incidence of adverse reactions and hepatic injury has not been emphasized as an important adverse reaction in Denmark. However worldwide, several cases of hepatic injury have been reported. We report one case of Captopril-induced hepatic injury. Despite discontinuation of Captopril a hepatorenal syndrome developed and the patient died five weeks after admission. This report emphasizes the need to be aware of the possibility of hepatic injury in patients receiving Captopril. PMID- 1413241 TI - [Hip surgery in Alborg and hospital management]. PMID- 1413242 TI - [Burns and "plastic bag therapy"]. PMID- 1413243 TI - Domain walls on graphite mimic DNA. AB - We show that domain walls on graphite are very likely to mimic features of extended macromolecules like DNA strands, when imaged with an STM. We explain with a simple model how different translational periods along a grain boundary originate from different relative orientations of the graphite lattice at the domain wall. We show how simple geometrical analysis of the images can be used to distinguish true macromolecular features from artifacts. PMID- 1413244 TI - Electrostatic spraying of DNA molecules for investigation by scanning tunneling microscopy. AB - We have investigated electrostatic spraying of DNA onto gold surfaces as an alternative sample-preparation technique for STM studies. Preliminary results show that a higher distribution of isolated strands as well as well ordered aggregates can be obtained with this technique when compared with electrodeposition or drop evaporation. In many places, the well ordered aggregates were found to cleave in a direction perpendicular to their length after repeated scanning in the same direction. PMID- 1413245 TI - Scanning tunneling microscopy of DNA: a novel technique using radiolabeled DNA to evaluate chemically mediated attachment of DNA to surfaces. AB - pBS+ plasmid deoxyribonucleic acid (DNA) was imaged by scanning tunneling microscopy (STM) after mounting microdroplets by aerosol deposition onto heated epitaxial gold surfaces. However, the instability of the adsorbate to forces exerted by the tunneling tip points out the need for more aggressive bonding of molecules to surfaces. We describe a sensitive assay for the qualitative and quantitative evaluation of chemical agents to influence binding of DNA to surfaces using 32P-labeled pBS+ plasmid DNA. We propose that such an assay can make an important contribution to immobilization techniques prior to STM imaging. PMID- 1413246 TI - Tip-radius-induced artifacts in AFM images of protamine-complexed DNA fibers. AB - Isolated DNA fibers complexed with protamine (the chromosomal protein that packages DNA in mammalian sperm) have been produced by partially decondensing the highly compacted mouse sperm chromatin particle on a glass coverslip. These DNA fibers were then scanned with the atomic force microscope (AFM). While the smallest of the fibers appear in AFM images as ribbon-like structures 250-350 A wide and 10-25 A high, experiments indicate that these images are the result of a convolution of the imaging-tip's shape with the object's actual shape. In such convolutions the height of the object is affected only by the compressibility of the object, while the width is affected in addition by the sharpness of the tip. Images of polyamidoamine particles also appear to show this artifact. We have also deduced the tip's radius of curvature from images of sharp steps and attempt to demonstrate the artifacts associated with a relatively large imaging tip. PMID- 1413247 TI - Imaging isolated strands of DNA molecules by atomic force microscopy. AB - We have employed an atomic force microscope (AFM) to image in air isolated strands of pBS+ plasmid DNA adsorbed onto freshly cleaved mica. At a DNA concentration below 0.3 micrograms/ml isolated strands of the plasmid DNA are usually seen, while for concentrations higher than 3 micrograms/ml a uniform coverage of interconnected DNA strands was observed. We found that the contrast and the width of DNA were dependent upon humidity. When the relative humidity exceeds 60%, negative contrast images with strand widths 20 times the width of DNA are found, while positive contrast images with 7 to 10 times the width of DNA are found when the humidity is below 30%. By placing the AFM in an environment where the humidity could be controlled, we were able to switch between positive and negative contrasts. PMID- 1413248 TI - Visualization of the algal polysaccharide carrageenan by scanning tunnelling microscopy. AB - Scanning tunnelling microscopy has been used to obtain images in the constant current mode in air and moist conditions at molecular resolution for the kappa- and iota-carrageenan algal polysaccharides. The molecules were deposited from an aqueous solution onto a graphite substrate. The samples formed aligned nematic like arrays and were also found as individual molecules. The molecular dimensions of width, height and repeat distance along the molecule were found to be close to the values previously determined by X-ray diffraction. The results support a molecular model based on a double-helix structure for carrageenan. PMID- 1413249 TI - Atomic force microscopy imaging of T4 bacteriophages on silicon substrates. AB - A new atomic force microscope incorporating microfabricated cantilevers and employing laser beam deflection for force detection has been constructed and is being applied to studies of biological material. In this study, T4 bacteriophage virus particles were deposited from solution onto electronic-grade flat silicon wafers and imaged in air with the microscope. Microliter droplets of the solution were deposited and either allowed to dry or removed with blotting paper. The images show both isolated viruses and aggregates of various sizes. The external structure as well as strands believed to be DNA streaming out of the virus could be observed. The construction of the microscope and its performance are also described. PMID- 1413250 TI - Streptavidin binding observed with an atomic force microscope. AB - An atomic force microscope (AFM) was used to investigate a specific recognition reaction: the binding of streptavidin to a biotinylated lipid bilayer. Prior to the recognition reaction, the phase coexistence of the lipid bilayer was clearly observed: fluid domains were lower than the crystalline domains. After introducing to the bilayer a very dilute solution of streptavidin to give a final concentration of approximately 0.5 microM, the recognition reaction was imaged in real time. Several hours later, we observed a contrast reversal, i.e., the previously lower fluid domains grew so much in height that they became higher than the crystalline domains. We found that the streptavidin molecules bound almost exclusively to the biotin in the fluid domain (less than 0.25% coverage of the crystalline domains). The apparent structure of the few streptavidin molecules bound to the crystalline domain of the bilayer is shown to depend on the applied force. Finally, in a 2-dimensional quasi-crystal in which the streptavidin molecules were compressed at the air-water interface molecular resolution was achieved. PMID- 1413251 TI - Molecular-resolution images of aspirin crystals with atomic force microscopy. AB - The atomic force microscope was developed in order to image arrays of molecules on the (001), (100) and (011) faces of aspirin crystals in water. Lattice spacings and symmetries of methyl groups and the part of the phenyl groups on the (001) face in water are consistent with X-ray diffraction data. Surfaces of the (100) face that show the best-developed cleavage, in general, are difficult to image. Although the lattice constant derived from (100) image is consistent with the X-ray diffraction data, the c-glide plane symmetry is lost and diffused spots are observed that are 1.8-3.1 times more elongated than (001) spots. It is not possible to image the (011) surface. This initial success in imaging the molecular crystal surfaces of drug compounds has clarified the different submolecular structures of the three different crystal faces, and the close relationship between the imaging difficulties and the differences in the dissolution process in water. PMID- 1413252 TI - Morphological difference between fibronectin sprayed on mica and on PMMA. AB - We have imaged with scanning force microscopy in air fibronectin (Fn) molecules sprayed on mica and on polymethylmetacrylate (PMMA), the latter being extensively used as biomaterial for implants. On mica we can observe small aggregates as well as individual molecules whose shape is influenced by the tip interaction during the scanning process, most of the isolated molecules showing a V-shape oriented in the scan direction. This indicates that the arms of the molecules are relatively free to move and the binding to the mica substrate is located near the disulfide bridge between the two subunits of the molecule. On the other side, when Fn molecules are sprayed on PMMA under the same conditions as for mica, we observe a thin network which we interpret as Fn molecules bound to each other. We relate our observation to the fact that mica is known to be strongly hydrophilic, which could reduce the Fn binding properties by interacting relatively strongly with molecules. On the other side, PMMA being hydrophobic, would interact less with molecules, leaving more binding sites for inter-molecular attachment. PMID- 1413253 TI - In situ investigations of single living cells infected by viruses. AB - In this paper we report the direct observation of biological processes on living cells. The experiments were done in situ by scanning force microscopy on a scale inaccessible by other techniques under physiological conditions. Living monkey kidney cultured cells were imaged under normal growth conditions and showed reproducible features on the 10 nm scale. Upon adding a suspension of pox viruses, characteristic changes of the cell membrane were repeatedly observed in different experiments on different cells. Almost immediately, a pronounced softening of the cell surface occurred which lasted only for a few minutes. More than two hours later very significant protrusions appeared to grow out of the cell membrane. These protrusions abruptly disappeared again. These events were only observed after infection and we interpret them as the exocytosis of proteins related to viral reproduction. After almost 20 h, a different type of event occurred which we interpret as the exocytosis of the progeny viruses themselves. PMID- 1413254 TI - Scanning force microscopy and cryo-electron microscopy of tobacco mosaic virus as a test specimen. AB - In this study, tobacco mosaic virus (TMV) provides a resolution criterion for specimen preparation methods as well as for imaging parameters of the scanning force microscope (SFM). We present scanning force microscopic images of the virus embedded in 0.5% buffered phosphotungstic acid solution adsorbed on a freshly cleaved mica surface, and imaged under atmospheric conditions. Individual TMV particles were clearly identified with a characteristic shape of long rods of about 300 nm long and 60-70 nm in apparent width due to the geometric parameters of the tip. The structure of the virus was compared with cryo-electron microscopic data of vitrified suspensions observed to a resolution of 1.15 nm. Uncoated TMV particles were also deposited on evaporated titanium thin films and imaged by SFM. PMID- 1413256 TI - Investigation of dialysis membranes with atomic force microscopy. AB - AFM was used to investigate dialysis membranes made of regenerated cellulose by the cuoxam process. The membranes were either Cuprophan or experimental samples, modified with different amounts of diethylaminoethylcellulose (DEAE). Atomic force microscopes with optical-lever detection systems were used to image the dry membranes in air as received from the manufacturer as well as wet membranes in a swollen state under water. Differences could be observed between modified and unmodified as well as between dry and wet membranes. PMID- 1413255 TI - Electrodeposition procedure of E. coli RNA polymerase onto gold and deposition of E. coli RNA polymerase onto mica for observation with scanning force microscopy. AB - Molecules of the transcriptional enzyme E. coli RNA polymerase (RNAP) have been deposited using three different deposition methods: (1) passive adsorption onto gold, (2) electrochemical adsorption onto gold and (3) adsorption onto mica. In all cases SFM imaging was straightforward and reliable, and surface coverage by the protein varied with deposition conditions as expected. To determine the nature of the electrochemical treatment on the gold substrate, cyclic voltammetry was performed with various chemical solutions. Finally, a comparison is made between the SFM images of RNAP obtained with these methods and STM images obtained earlier. Both STM and SFM show strikingly similar results; however, heights and widths of individual molecules differ. PMID- 1413257 TI - Is it possible to observe biological macromolecules by electrostatic force microscopy? AB - Biological macromolecules such as proteins are charged species in solution. The exact charge depends upon the pH, temperature and ionic strength of the medium in general. This suggests the possibility of employing electrostatic force microscopy as a useful tool for the observation of these macromolecules. Our calculations show that electrostatic forces could be used for this purpose, thus helping to remove ambiguities in the location and identification of proteins. The long-range nature of electrostatic forces could make them useful to locate these macromolecules on the appropriate substrate while, at the same time, overcoming important disturbing effects such as lateral displacement of the macromolecules or destructive contact with the sample. PMID- 1413258 TI - Imaging of subunit complexes of thermophilic bacterium H(+)-ATPase with scanning tunneling microscopy. AB - Using a scanning tunneling microscope (STM), we observed reconstructed subunit complexes of H(+)-ATPase of a thermophilic bacterium. The measurement was carried out in air without conductive coating on the samples deposited on a highly oriented pyrolytic graphite (HOPG). The F1 subunit complex of the H(+)-ATPase, and an H(+)-ATPase whose F0 portion was embedded into liposomes prepared from soybean lecithin were imaged. Overall structural images of the subunit complex F1 were obtained: the structural dimensions of the STM images are in agreement with those deduced from conventional methods such as an transmission electron microscopy (TEM) and small-angle X-ray scattering (SAX) experimentation. Regarding the STM imaging of these samples, we discuss the advantages and disadvantages of the STM over those of conventional methods such as a TEM and SAX. PMID- 1413259 TI - Imaging of proteins by scanning tunnelling microscopy. AB - Scanning tunnelling microscopy has been used to examine the structure of proteins deposited on a graphite surface. Three molecules have been studied; immunoglobulin G (IgG), Complement component 1q (C1q) and ATP-citrate lyase (ACL). The images show IgG as a tri-lobed molecule, consistent with the known 3D structure as determined by X-ray crystallography. The C1q images differ from the well known "tulip bunch" model derived by electron microscopy, but are consistent with the model if it is assumed that the six globular heads have aggregated. Molecules of ACL are visible as discrete units, with some hints of substructure. These results highlight the potential of STM in studying protein structures, but also illustrate the difficulties of interpreting micrographs of proteins whose structure is currently unknown. PMID- 1413260 TI - Molecular images of cereal proteins by STM. AB - Scanning tunnelling microscopy (STM) has been used to study a seed storage protein of wheat known as gamma-gliadin. The protein was deposited onto highly oriented pyrolytic graphite (HOPG) from solutions of trifluoroethanol (TFE) and 1% acetic acid. Samples were dried down and then scanned in air. Transmission electron microscopy (TEM) was also used to visualise the distribution of protein on the substrate. Small-angle X-ray scattering (SAXS) was used to compare the molecular size and shape obtained with those from the STM images. PMID- 1413261 TI - Scanning force microscopy studies of the S-layers from Bacillus coagulans E38-66, Bacillus sphaericus CCM2177 and of an antibody binding process. AB - In many prokaryotic cells (eubacteria and archaebacteria) the outermost cell envelope component is composed of a regularly structured protein surface layer (S layer). The two-dimensional S-layer from Bacillus coagulans E38-66 and Bacillus sphaericus CCM2177 has been investigated by SFM at molecular resolution under physiological conditions (i.e., in buffer solution). We find the E38-66 S-layer lattice to be oblique with lattice parameters of a = 9-10 nm, b = 7-8 nm and gamma = 80 degrees -90 degrees (E38-66). The CCM2177 lattice is square with a = 12-14 nm, in good agreement with TEM data. We have used the unique possibility of the SFM to study the kinematics of biological processes and have performed experiments on the adhesion of polyclonal antibodies to the recrystallized E38-66 protein layer on a time scale of about two to ten seconds per image frame. This represents a first step in directly visualizing molecular recognition reactions. PMID- 1413263 TI - Deposition and imaging of metal-coated biomolecules with the STM. AB - We have applied a simple and reliable procedure for imaging biomolecules with the scanning tunneling microscope (STM). The biomolecules are adsorbed on glow discharged mica, then coated with a thin film of platinum-carbon. We have tested this method with linear and circular (plasmid) DNA molecules. The contrast and resolution of the STM images are comparable to electron micrographs of the same molecules when shadowed. Though the present lateral resolution (5-6 nm) is limited by the grain size of the conductive film, some details like supercoiled regions in the DNA are resolved. This method is interesting for two reasons. First, as an alternative technique for imaging biomolecules. Second, for use as a control in STM studies of bare biomolecules. PMID- 1413262 TI - Substrate preparation for reliable imaging of DNA molecules with the scanning force microscope. AB - A simple method of substrate preparation for imaging circular DNA molecules with the scanning force microscope (SFM) is presented. These biomolecules are adsorbed onto mica that has been soaked in magnesium acetate, sonicated and glow discharged. The stylus-sample forces that may be endured before sample damage occurs depends on the ambient relative humidity. Images of circular DNA molecules have been obtained routinely using tips specially modified by an electron beam with a radius of curvature, Rc, of about 10 nm [D. Keller and C. Chih-Chung, Surf. Sci. 268 (1992) 333]. The resolution of these adsorbed biomolecules is determined by the Rc. At higher forces individual circular DNA molecules can be manipulated with the SFM stylus. Strategies to develop still sharper probes will be discussed. PMID- 1413264 TI - How useful are acceleration- and deceleration-based Doppler indices? A trial on patients with percutaneous transluminal angioplasty. AB - The usefulness of indices commonly used in Doppler sonography is limited; the aim of this study was to investigate if inclusion of systolic acceleration and deceleration patterns in Doppler indices will result in practical diagnostic advantages. Systolic delay time index (SDTI) and height-width index (HWI) are compared to Gosling's pulsatility index (PI) and to PI-based damping factors (DF) in patients with isolated lesions in the distal superficial femoral artery before and after percutaneous transluminal angioplasty (PTA). Before PTA, all indices distal to the lesion differ significantly from proximal indices. After successful PTA, none of the indices is able to detect the PTA outcome with sufficient sensitivity. The additionally defined curve broadening index (CBI) shows a 100% sensitivity for detecting PTA success in the examined patient population. PMID- 1413265 TI - Modelling the feto-placental circulation: 1. A distributed network predicting umbilical haemodynamics throughout pregnancy. AB - The modifications of the Doppler flow velocity parameters occurring in the feto placental circulation throughout pregnancy have been reproduced on the basis of a mathematical model. Some simple assumptions were made, such as the progressive development of a dichotomous villous vessel network and the increase of the perfusion pressure and of the umbilical arteries dimensions throughout pregnancy. Moreover, both the viscous and capacitive characteristics of the vascular bed were taken into consideration in order to predict the mean values of blood volume, flow and velocity and the pulsatility index. Their value is shown to depend on few parameters, and mainly on the cross-sectional area ratio between the vessels belonging to two succeeding generations. PMID- 1413266 TI - Modelling the feto-placental circulation: 2. A continuous approach to explain normal and abnormal flow velocity waveforms in the umbilical arteries. AB - A mathematical model of the feto-placental circulation which describes the development of the placental vasculature throughout pregnancy on the basis of simple assumptions is used to simulate some abnormalities of the villous vascular tree which may affect the values of Doppler indices. In normal cases, the model shows a decreasing trend of the pulsatility index (PI) throughout pregnancy which is comparable to that observed in vivo. When a pathological interruption of the villous growth is simulated, the PI does not decrease any further, unless the input pressure keeps increasing. When various degrees of obliteration of the villous tree are simulated, either through an occlusive process or a reduction of the lumen of the vessels, the PI values increase and the volume flow decreases to a greater extent. The data predicted by the model are compared to those obtained in clinical studies and in experimental animal models. PMID- 1413267 TI - In vitro classification of gallstones by quantitative echography. AB - Gallstones (n = 20) were classified by dual energy Computer Tomography (CT) into three main classes: pure cholesterol stones (I), combination stones (II) and calcium stones (III). Further subclassification was possible by using morphological criteria. The acoustic measurements that were performed were measurements of the velocity of sound, the attenuation coefficient slope with frequency and intercept at 4.5 MHz, the attenuation coefficient slope per unit of time, the backscattering characteristics, and the appearance of B-mode echograms. The velocity of sound in calcium stones (c = 1695 +/- 107 m/s) was distinctly lower than in those containing some cholesterol (c > 2000 m/s). The attenuation coefficient slope ranged from 4.3 to 16.2 dB/cm MHz, the 4.5 MHz intercept from 21 to 66.2 dB/cm. The lowest values were found for the pure cholesterol stones (class IA), the highest values for subclass IIB (combination stones with shell). The attenuation coefficient slope per unit of time was distinctly lower (< 0.50 dB/microseconds MHz) for the cholesterol stones than for the combination and calcium stones (>0.64 dB/microseconds MHz). The backscattering spectrum was approximated by a straight line fit, and the slope for the cholesterol stones was lower than for the combination and calcium stones (<0.75 dB/MHz vs. >1.0 dB/MHz, respectively). The latter two parameters were assessed by in vivo applicable methods. The front echo level was found to be more than 5 dB higher for class IIB as compared to the other classes, while the spectral backscatter level at 4.5 MHz was considerably higher for both classes IIB and III. The B-mode echograms showed that a strong front echo in combination with a strong attenuation of the remaining echo signals was mainly found for stones of classes IIB and III. A significant difference between the group of stones that are suitable for lithotripsy and dissolution treatment (classes IA, IB and IIA) and the nontreatable calcium-containing stones (classes IIB and III) was found for the velocity of sound (p <0.01), the attenuation coefficient slope per time unit (p <0.10), the slope of the backscattering spectrum (p <0.05) and the 4.5 MHz intercept (p <0.01). B-mode classification yielded no complete distinction of these two groups of stones. It can be concluded that in vivo assessment of quantitative characteristics (front reflection, backscattering characteristics, attenuation coefficient slope per unit of time) in combination with the B-mode characteristics might be useful for in vivo gallstone classification. PMID- 1413268 TI - An attempt to reconstruct the lithotriptor shock wave pulse in kidney: possible temperature effects. AB - Based on measurements carried out in water in two lithotriptor systems, the authors have made an attempt to reconstruct numerically amplitudes and shapes of shock wave pulses penetrating into kidney which differ from those in water. The difference between these pulses and those observed in water was analyzed and was also demonstrated experimentally. The amplitude and the steepness of the reconstructed pulse front were shown to be much lower than in water depending on the distance of the kidney stone from the patient's body surface. For a distance equal to 4 cm, the shock wave pulse amplitude of 40 MPa in water was estimated to decrease in the kidney by a factor of about two and the steepness of the positive shock pulse front to decrease several times. The analysis was carried out by considering the possible changes of absorption and attenuation in tissues which increase in an unknown way with the wave amplitude. It was shown that the temperature elevation caused by the increase of nonlinear high amplitude absorption is limited due to a corresponding increase in attenuation of the shock wave penetrating soft tissues. The temperature elevation was estimated on the basis of this work to be at most 1.8 times that one estimated in the case of two considered lithotripsy systems when assuming small amplitude absorption and attenuation coefficients. PMID- 1413269 TI - Red cell aggregation and the echogenicity of whole blood. AB - To study the relationship between red cell aggregation and whole blood echogenicity, red cell aggregation was quantitated by a photometric method, whole blood echogenicity was quantitated by videodensitometry and sedimentation rate was quantitated by a modified Westergren method. Changes in red cell aggregation were produced by alterations in the hematocrit. The results showed that red cell aggregation increased in a linear fashion with increases in hematocrit. The sedimentation rate decreased in a linear manner with increases in hematocrit. Whole blood echogenicity showed a biphasic response, with an initial increase in echogenicity, peaking at hematocrits varying from 14-24% and decreasing thereafter. Over the physiologic range of hematocrits, an increase in the formation of red cell aggregates is associated with a decrease in the echogenicity of whole blood. Thus, red cell aggregates were not visible using our ultrasound equipment at physiologic hematocrits, and the echo contrast in blood under our experimental conditions at these hematocrits must represent either plasma spaces, platelet aggregates or possibly white cell aggregates. The association between spontaneous contrast and a propensity for thromboembolism imply that platelet aggregates are the most likely origin of in vivo echo contrast in flowing blood. PMID- 1413270 TI - Identifying acoustic scattering sources in normal renal parenchyma in vivo by varying arterial and ureteral pressures. AB - Ultrasonic backscatter properties of normal dog kidney parenchyma are examined in vivo to determine sources of acoustic scattering. We systematically varied the renal perfusion and ureteral pressures to obtain detailed information about scattering sources that could not be seen under in vitro conditions. These data suggest that in normal parenchyma the principal sources of backscatter are Bowman's capsule at low frequencies (2.5-5.0 MHz) and glomerular arterioles at high frequencies (5.0-15.0 MHz). We found that the integrated backscatter coefficient (IBC) in normally perfused kidney cortex is approximately half that measured in the ischemic organ at all frequencies. Ischemia was found to reduce scatterer size estimates (D) by 10% at low frequencies and increase D54% at high frequencies. Acute obstruction of the kidney, under diuresis, produced an 11% increase in D at low frequencies, and no significant change in D at high frequencies. These variations in backscatter measurements are explained in terms of changes in the microscopic anatomy of the kidney. PMID- 1413271 TI - Conservation of bactericidal activity in ultrasound-exposed murine peritoneal phagocytic cells. AB - Murine peritoneal exudate cells (PEC), predominantly macrophages, were insonated in vitro with burst-mode ultrasound and assayed for their ability to phagocytose and kill Staphylococcus aureus. PEC were exposed at 37 degrees C in rotating tubes to 1-MHz, burst-mode (10 ms on, 10 ms off) ultrasound at 3.7 +/- 0.2 W/cm2 ISPTA (7.4 +/- 0.4 W/cm2 ISPBA) for 150 s. Bactericidal activity was assayed at 1, 2, and 3 h after exposure and subsequent 37 degrees C incubation with the bacteria for 20 min. In these experiments, which comprised 17 treated and 7 sham treated control samples, there was no significant difference in results between treated and control samples (p > 0.29). PMID- 1413272 TI - Ultrasonic vibrational potentials in gels and preparations of biological tissue. AB - Measurements of the ultrasonic vibrational potentials (UVP) were performed at 815 kHz in agar and agarose gels as well as in several biological tissues from frog, rat and pig. The results for gels show that the magnitude of the UVP depends on the charge of the solid components of the gel, its mechanical strength and particularly on the concentration of free electrolytes present in the gel. The UVP decreases to less than 10 microV for a velocity amplitude of 1 cm/s if the salt concentrations exceed 10(-2) mol/L. The measurements in biological tissue in vitro demonstrate that the UVP are of the order of magnitude of a microV s cm-1 which is also explained by the presence of electrolytes of high concentrations in tissues. The measurements in biological tissue in vitro demonstrate that the UVP are of the order of magnitude of microV s cm-1 which is also explained by the presence of electrolytes of high concentrations in tissues. Based on these experiments, it can be concluded that the potential for harm to humans due to electrical effects of ultrasound as used in medical diagnostics is very low. PMID- 1413273 TI - Influence of dissolved and free gases on iodine release and cell killing by shock waves in vitro. AB - Exposure of a potassium iodide solution to lithotripter shock waves resulted in formation of iodine with the amount of iodine depending on the gas dissolved in the solution. Iodine yield was higher with O2 and Ar, as compared to CO2 and N2O; degassed solution revealed the lowest iodine yield. Exposure of L1210 mouse leukemia cells to shock waves reduced the number of viable cells with no difference between O2-, Ar-, or N2O-equilibrated and degassed conditions. CO2 equilibration resulted in a more pronounced reduction. The difference between chemical and biological effects argues against the involvement of free radicals in cell killing by shock waves. In additional experiments, gas bubbles of various sizes were introduced into the test vials. Addition of a 10 microL gas bubble revealed an over 10-fold increase in iodine yield from degassed potassium iodide solution with all gases. Addition of a gas bubble also reduced the number of viable cells again with no difference between the gases. It is suggested that shock wave-gas bubble interaction is an important mediator of iodine release and cell killing by shock waves. PMID- 1413274 TI - The influence of spatial polarization distribution on spot poled PVDF membrane hydrophone performance. AB - The influence of spatial polarization distribution on spot poled PVDF membrane hydrophone performance was calculated and then experimentally verified using a one-dimensional model based on acoustic wave propagation through a layered medium. It is shown that the sensitivity of the hydrophone is markedly dependent on the spatial polarization distribution. It is also shown that there can be a significant difference between the voltage sensitivities measured in the same hydrophone probe depending on which electrode is actually facing the acoustic source. The measurements carried out in the frequency range 1-20 MHz indicate that this difference, while negligible below 2 MHz, may exceed 1.6 dB at higher frequencies. The model developed can also be used to determine the "effective" piezoelectric constant d33 of the PVDF material as a continuous function of frequency. Moreover, the model predicts the existence of a negative slope in the frequency response of the spot poled membrane hydrophone. The experimental confirmation of this prediction underscores the importance of using swept frequency methods during calibration measurements. PMID- 1413275 TI - Continuous and simultaneous ultrasound Doppler velocimetry of the internal carotid and vertebral arteries: preliminary observations of cerebral blood flow changes with common carotid compression. AB - We have developed a new technique for simultaneous assessment of the four cervical cerebral arteries. Using a cervical brace with four freely adjustable Doppler probes attached, we studied four healthy young males and observed their cerebral blood flow changes during common carotid compression. The results indicated various reactivity in these subjects. We observed that carotid compression sometimes affects or stops the ipsilateral vertebral flow according to the intensity and location of compression. Also, the flow of the contralateral internal carotid artery (ICA) and vertebral artery (VA) showed remarkable increases greater than those due to ICA obliteration alone. This indicates the possibility that using only one probe during compression may often result in unknown obliteration of the ipsilateral VAs flow and could also produce other incomplete data. Moreover, with our technique, we would be able to assess the cerebral reserve more precisely and clearly in patients with carotid or vertebral occlusive diseases. PMID- 1413276 TI - The assessment of benign uterine tumor vascularization by transvaginal color Doppler. AB - Transvaginal color flow Doppler was used to study uterine flow and fibroid arterial supply. These studies were carried out in 101 patients with palpable uterine fibroids and 60 women attending the clinic for annual checkups. Blood flow impedance expressed as resistance index (RI), pulsatility index (PI), and blood velocity are calculated from the 5th to the 8th day of the menstrual calendar. Increased blood velocity and decreased RI and PI in both uterine arteries occurred in patients with uterine fibroids. The same technique was also used to study blood flow in the main arteries supplying identifiable fibroid. Diastolic flow in these arteries was always present and increased in comparison with uterine artery blood flow. The difference in uterine artery blood flow between patients with fibroids and healthy volunteers is statistically significant and may have predictable value in growth rate evaluation of the benign uterine mass. PMID- 1413277 TI - Colour Doppler velocity imaging of the myocardium. AB - A technique has been developed for producing images of the velocity of tissue motion within the myocardium. It has been demonstrated that Colour Flow Doppler imagers can be operated to depict the velocities within the myocardium rather than moving blood in the cardiac chambers. The technique exhibits the normal advantages of diagnostic ultrasound, i.e., real-time imaging with relatively inexpensive equipment and no hazard to the patient. Further work requires to be done to determine the optimum signal processing algorithms for moving tissue echoes and to ascertain whether the technique is of value in clinical applications. PMID- 1413278 TI - [Penetrating thoracic injuries]. AB - In a period of peace in Germany and other westeuropean countries, penetrating trauma of the thorax (PTT) is much more rarer than blunt trauma. An analysis of 103 patients with PTT, treated in the Surgical Department of the University of Cologne from 1980 to 1990, showed, that these are usually isolated injuries in young patients. These occur usually following violence as stab wounds and less commonly gunshot wounds. Two thirds of the patients could be treated adequately with intensive care therapy and the use of thoracic drains. One third of the patients underwent thoracotomy, which was carried out in two thirds within one hour after hospital admission and in the remaining one third within the first 24 hours. The mortality for all PTT was 13%, being 10% for isolated thoracic injuries and 19% for patients with multiple trauma. PMID- 1413279 TI - [Clinical criteria of acute epidural hematoma]. AB - In a retrospective study 368 epidural hematomas are presented, treated from 1970 until August 1991. The clinical course and manifestation of acute epidural hematomas is commented on by means of own cases. Assessing the success of treatment, it could be demonstrated that the prompter diagnosis reduced the lethal outcome of epidural hematoma to 6.6%. PMID- 1413281 TI - [Damage to the knee ligament as a concomitant injury in femoral shaft fractures]. AB - Knee ligament injuries associated with femoral shaft fractures can severely influence the functional results of treatment. In a follow-up of 59 operatively treated femoral shaft fractures 18.6% of the patients revealed ligamentous damages. In all cases one or both of the cruciate ligaments were injured. Especially polytraumatized car front-seat passengers are at higher risk with 30.8% ligament ruptures. While only 61.6% of the ligament injuries were primarily diagnosed, the testing of knee joint stability after osteosynthesis of a femoral fracture is essential. Furthermore arthroscopy should be performed if there is any hint of ligamentous damage. The ruptures of the anterior cruciate ligament and the ligamentous avulsion fractures can be successfully treated on by operative means. PMID- 1413280 TI - [MR and ultrasound study of Achilles tendon injury]. AB - In 24 patients with lesions of the achilles tendon MRI and ultrasound was performed to compare the results with clinical examination. MRI had an accuracy of 100%, ultrasound of 90%. Especially partial rupture with chronic degenerative lesions of the tendon can be diagnosed more accurate by MRI which enables easier indication for treatment. By MRI diagnostic differentiation of our patients in four groups was possible. PMID- 1413282 TI - [The value of sonographic diagnosis of the injured knee joint in trauma-surgical practice]. AB - In a period of two years (January 1990 to December 1991) 136 knee joints were examined by ultrasound and arthroscopy. 40 out of 42 arthroscopically proven lesions of the anterior cruciate ligament were detected by ultrasound. The sensitivity therefore was 95.24%. We found three cases of ruptures of the posterior cruciate ligament, which were not detected clinically. 16 cases of ruptured medial collateral ligaments and 27 cases of elongations of the same ligament were diagnosed. Ultrasound examination of the knee and especially of the cruciate ligaments showed to be an accurate tool in order to obtain additional information on an injured knee even if clinical examination is difficult or impossible. Sonography is able to exclude lesions of the cruciate ligaments precisely. Therefore it helps to restrict the necessity of acute or early arthroscopy of knee joints. PMID- 1413283 TI - [Bilateral tibial head epiphysiolysis in somersault jumping]. AB - We are reporting about a rare case of a bilateral epiphyseal separation of the proximal tibial epiphysis which occurred to a 16 year old male at the time of bileged take-off when somersault diving. The X-rays at admission showed a bilateral proximal tibial epiphyseal separation of Salter-Harris type I on the right side and Salter-Harris type II on the left side. Both epiphyses showed a posterior dislocation. Stable, anatomical position on both sides was achieved by closed reduction under general anaesthesia and fixed by a plaster cast for five weeks. Healing occurred in anatomical position and no redislocation or growth disturbance was observed. The treatment for such separations is usually conservative; the prognosis is very good, provided that an optimal reposition with restoration of the anatomical situation has been achieved. PMID- 1413285 TI - [PC-assisted planning and documentation of the surgical schedule]. AB - A computer program for personal computers was developed to support and control the schedule in the operation theatre. With this program a great amount of operational and medical data will be recorded (e.g. the duration of operation and anesthesia, the number of operating rooms occupied, the personnel involved, the diagnosis and surgical therapy). The screen shows up-to-date information about the ongoing events. All data can be easily evaluated for different criteria. In a four years period the program presented has proved valuable for daily routine planning and documentation in a great operation unit. PMID- 1413284 TI - [Initial experiences with the humerus interlocking nail]. AB - A preliminary report is given on the good results of eleven patients, who had been treated with a locking nail for a fracture of the humerus at three different trauma departments. No non-union, infection or radial palsy has been seen nor was there any neurovascular complication intraoperatively. Four patients had misalignments of up to 15 degrees, whereof three of them had combined varus recurvation-angulations without functional or cosmetic sequelae. All but one had excellent functional results six months postoperatively. Bone healing could be confirmed three months postoperatively. Only transverse and spiral fractures of the second to fifth sixth had been treated until now, though open fractures up to the second degree can be managed too. Finally, some technical issues are considered, which include a better guiding device, the use of cancellous screws for proximal looking, a more oblique position of one of the proximal screwholes to obtain some kind of interfragmentary compression for appropriate fractures, and the use of a Williams-screwdriver. PMID- 1413286 TI - [The status of surgical continuing education in Germany]. PMID- 1413287 TI - [Comment on G. Sowa, J. Sowa, J. Koebke: Alloplastic replacement of the anterior cruciate ligament]. PMID- 1413288 TI - [Comment on T. Raslan, W. Wartenburger: Case report of isolated dislocation fracture of the os trapezium]. PMID- 1413289 TI - [Infections in children: prevention and treatment. Interview by Isabelle Lecomte]. PMID- 1413290 TI - [Hospitals and the university mission]. PMID- 1413291 TI - [An effective intervention project for arterial hypertension screening in family medicine]. AB - This study was carried out to assess the effectiveness of a preventive protocol in improving hypertension detection in a hospital-based family medicine unit. This protocol was planned and implemented by local practitioners and did not need any additional budgeting. Two distinct groups, each of 850 adults, were randomly selected from patients having consulted before and after the introduction of the protocol. Medical records were audited. Hypertension screening rate improved of 17.7% (p less than 0.00001) after the application of the preventive intervention. Furthermore, a 20.5% increase of the screening rate was estimated after adjustment by the logistic regression method, for characteristics related to patients and to practitioners. In conclusion, these findings support the hypothesis that this preventive protocol contributes to improve in family physicians their hypertension screening performance and they justify further assessment with a control group. PMID- 1413292 TI - [Radiological consultation]. PMID- 1413293 TI - [Mammography]. AB - Mammography is the most important method for the diagnosis and the screening of breast diseases. Sensitivity and accuracy of mammography are very high in the detection of breast cancer. The use of the stereotaxic localization and fine needle aspiration of nonpalpable breast lesions improve its effectiveness. The American Breast Cancer Detection Demonstration Project (BCDDP) has demonstrated the benefits of breast screening for women over 40 years of age. Many American medical associations and societies have adopted the guidelines based on the BCDDP results, promoting breast cancer screening for these women. However, recently released results of some randomized breast screening studies demonstrated only a 5% reduction in mortality from breast cancer in women 40-49 years of age, and a 40% reduction for women aged over 50 years. There is no explanation for this dilemma at the present time. However, screening mammography should stay available for women over 40 years of age. PMID- 1413294 TI - [Periodical medical examination update 1991: 3. Secondary prevention of prostate cancer. Canadian study group on the periodical medical examination]. PMID- 1413296 TI - [Alopecia: to avoid certain predispositions, to prevent, to control. Interview by Robert Henry]. PMID- 1413295 TI - [Alopecia: a good way to interrupt the fall... Interview by Robert Henry]. PMID- 1413297 TI - Cytogenetic evidence of intratumoral focal heterogeneity in prostatic carcinomas. AB - Although prostatic cancer is the most common malignant disease in men in western countries, only limited data on chromosomal changes are available. We report on our cytogenetic findings in cell cultures from four primary prostatic carcinomas indicating the existence of intratumoral focal heterogeneity concerning chromosomal anomalies in prostatic cancer. PMID- 1413298 TI - Tumor size of renal cell carcinoma: its clinical implication. AB - We studied the clinical implication of tumor size in renal cell carcinoma, by revealing its relation with the other histopathological and clinical features. The tumor size was well correlated with histopathological findings and metastatic status of the carcinoma. Smaller carcinomas (usually less than 60 mm) generally had a higher disease-specific survival than those of 60 mm or greater. The results indicated that the size reflected the biological character of the carcinoma. However, 10% of patients with the smaller carcinoma had lymph node metastasis or distant metastasis at the time of diagnosis, each of which contributed to a renal cell carcinoma-related death in the early follow-up period. PMID- 1413299 TI - Partial ureteric obstruction in weanling rats. II. Long-term effects on renal function and arterial blood pressure. AB - A partial obstruction of the left ureter was created in weanling (3-week-old) rats. Renal function was studied after 7-9 weeks and compared to that in age matched controls. Arterial blood pressure was found substantially increased. During normal hydration, the hydronephrotic kidney had low excretions of urine, potassium, osmoles and, especially, sodium. The contralateral, intact side showed no compensatory traits. On volume expansion, the hydronephrotic kidney demonstrated an unimpaired reacting capacity, leading to normalization of urine, sodium and osmole excretions and even to supernormal renal blood flow, glomerular filtration and potassium excretion. On the intact side, the excretion of potassium was increased like that on the hydronephrotic one, while excretions of urine, sodium and osmoles were increased even more. The fact that the intact kidney handled most of the urine excretion was interpreted as the result of a mechanism protecting the obstructed kidney from additional pressure insults while homeostasis was maintained. The arterial hypertension may result from the combination of retention of fluid and sodium by the hydronephrotic kidney and the absence of compensation by the intact kidney during normal hydration--like that in everyday life. The functional changes during normal hydration were generally more severe than those we found after obstruction in neonatal and adult rats, in which arterial hypertension was never observed. The clinical implication would be that the kidney may be less tolerant to pressure rises during the infant year. Changes due to obstruction are known to occur rapidly, but after that neither progress nor reverse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413300 TI - Adenosine triphosphate and adenosine diphosphate in human semen: correlation with sperm count and motility. AB - Adenosine triphosphate (ATP) and adenosine diphosphate (ADP) have been correlated with traditional semen parameters such as forward motility and sperm count. ATP and ADP were determined by a bioluminescence assay using the luciferin-luciferase reaction. Short boiling of the ejaculate was performed to inactivate phosphatases (ATPases) in the seminal plasma and the sperm tails. Fresh and deep-frozen semen samples from 45 men with oligozoospermia (n = 22) and normal sperm count (n = 23) were evaluated. Freezing of the sperm for 12 weeks did not effect the ATP or ADP content in the spermatozoa as compared to fresh semen. ATP and ADP concentration was in the range of picomoles/microliter and showed a significant correlation with the number of normal sperm per milliliter and a less marked correlation with the sperm motility. ATP and ADP concentration in the spermatozoa can be measured relatively easy and is reproducible. Unlike the monotonous evaluation of sperm motility by a technician, this biochemical method provides an objective parameter for semen quality. These qualities suggest that this method could be a way to determine the fertilizing potential of semen and to relate this to actual pregnancy rates. PMID- 1413301 TI - Urinary tract infection caused by nontyphoidal Salmonella: report of 30 cases. AB - Thirty cases of nontyphoidal Salmonella bacteriuria were identified by review of cultures performed at the Mayo Clinic (Minn.) from 1985 to 1989 and at the Federal Public Health Laboratory Innsbruck (Austria) from 1979 to 1989. All patients had symptoms of an acute urinary tract infection (UTI). In 24 cases nontyphoidal Salmonella was the sole pathogen isolated. Only 1 patient presented with concomitant gastroenteritis and 2 had experienced episodes of diarrhea during the weeks before the UTI, but 15 patients had positive stool cultures in the absence of a gastrointestinal illness. Among all positive urine cultures at the Mayo Microbiology Laboratory, 0.015% were positive for nontyphoidal Salmonella; at the Federal Public Health Laboratory Innsbruck, 0.024% of organisms cultured from urine were nontyphoidal salmonellae. In the majority of our patients, Salmonella UTI did not differ clinically from UTI caused by other members of the Enterobacteriaceae; only in renal transplant recipients was the course of genitourinary salmonellosis more serious. While some urinary isolates of nontyphoidal Salmonella may be fecal contaminants, all 30 isolates recovered from urine during this study were considered to be the cause of symptomatic UTI. PMID- 1413302 TI - Efficacy of prophylactic gentamicin use in postoperative urinary tract infections after endoscopic procedures of the urinary tract. AB - In this study, the efficacy of prophylactic antibiotic use was investigated. A total of 110 patients undergoing endoscopic procedures of the urinary tract were enrolled in the study. Fifty-five of the patients were treated with 8-hourly, 80 mg gentamicin sulfate of total three doses. The drug administration began just prior to the operation. Seven postoperative infections (12.7%) were detected, the same number as in the control group of 55 patients. The results confirm that there is no place for gentamicin prophylaxis in endoscopic procedures of the urinary tract. PMID- 1413303 TI - Inhibitors of calcium oxalate crystallization and urolithiasis. AB - In urolithogenic processes both, promoters and deficit of inhibitors, play an important role. The inhibitory action of added inhibitors (magnesium, citrate, pyrophosphate and chondroitin sulphate) was investigated using the urine of 72 patients with calcium urolithiasis. It was concluded that the deficit of inhibitors seems to be an important cause of stone formation in idiopathic oxalocalcic urolithiasis. Nevertheless, when that specific heterogeneous nucleation takes place it becomes an important factor and the inhibitor plays a complementary role in calcium oxalate urolithiasis. PMID- 1413304 TI - Renal damages after extracorporeal shock wave lithotripsy evaluated by Gd-DTPA enhanced dynamic magnetic resonance imaging. AB - Renal damages after extracorporeal shock wave lithotripsy (ESWL) were evaluated by magnetic resonance imaging (MRI) including Gd-DTPA-enhanced dynamic MRI in 37 patients with renal stone by spin echo methods (T1 and T2-weighted scan) and small tip angle gradient echo method (T2-weighted scan). Sixty-eight percent of the patients had changes in the MRI findings after ESWL. The frequently observed findings were perirenal fluid collection (38%), loss of corticomedullary junction (35%), and increased signal intensity of muscle and other adjacent tissue (34%). Preoperative Gd-DTPA-enhanced dynamic MRI showed low intensity band which suggests Gd-DTPA secretion from the glomerulus into the renal tubulus. In all cases the low intensity band became unclear after ESWL because of renal contusion due to ESWL. MRI, including Gd-DTPA-enhanced dynamic MRI, is considered to be a good procedure for evaluation of renal damages due to ESWL. PMID- 1413305 TI - Effect of extracorporeal shockwave lithotripsy for urolithiasis on concentrations of creatine kinase isozymes in patient serum and urine. AB - To determine whether extracorporeal shockwave lithotripsy (ESWL) for urolithiasis causes renal injury, we immunoassayed creatine kinase isozymes (CK-B and CK-M) in serum and urine from patients with renal stone (n = 21) and ureteral stone (n = 18) before and after (0, 2, and 24 h) ESWL. CK-B is generally present in renal tissue at relatively high concentrations, whereas CK-M is found at low concentrations. CK-B and CK-M levels were enhanced both in the serum and urine samples after ESWL in both groups of patients but CK-B levels return to almost normal very rapidly. Because CK-M, which is mainly localized in muscle tissue, also increased in both groups, the increased CK-B in serum after ESWL might be derived not only from kidney but also from muscle tissues which also contain a significant level of CK-B. These results suggest that significant tissue injury, including kidney and muscles, might be caused by ESWL treatment for urolithiasis but there is no long-term renal adverse effect, and that creatine kinase isozymes in serum and urine might be useful markers of tissue injury by such treatment. PMID- 1413306 TI - An azoospermic male with reciprocal translocation t(3;4)(p12;q21). AB - We report a case of autosomal translocation associated with azoospermia. The literature is reviewed, and hormone condition and testicular histology are discussed. PMID- 1413307 TI - Surgical reinforcement of gender identity in adolescent intersex patients. AB - The presentation of phenotypic gender ambiguity at the time of adolescence is uncommon. Surgical reinforcement of gender, or reassignment is often complex and multistage. We present 2 cases of children who developed secondary sexual characteristics contrary to their chromosome status who, because of their late presentation, required significant surgical intervention to reinforce the gender assigned to them. We review some of the surgical techniques involved. PMID- 1413308 TI - Urethral narrowing due to ectopic prostatic tissue in the bulbar urethra. AB - Ectopic prostatic tissue in the bulbar urethra is a rare disorder. A case of urethral narrowing due to such tissue is presented. The tissue specimen from the urethral narrowing was positively stained immunohistochemically by the prostatic specific antigen. Urethrocystographic findings are also discussed. PMID- 1413309 TI - Urethral tuberculosis. AB - Tuberculous affection of the urethra is very rare. Herein we report 2 cases of urethral tuberculosis. One in a young married female who had isolated urethral involvement presenting as urethral caruncle and the second in a young male with urethral stricture complicated by fistulae and abscess in association with renal tuberculosis. The relevant literature is briefly reviewed. PMID- 1413310 TI - Abscess of corpus cavernosum. AB - A rare case of abscess of the corpus cavernosum is described. Culture of the abscess yielded beta-hemolytic streptococcus. Ultrasound scan and cavernosography confirmed the physical examination findings of involvement of the corpus cavernosum. The patient was treated successfully by percutaneous ultrasound guided aspiration drainage and systemic antibiotic therapy. PMID- 1413311 TI - Spontaneous thrombosis of the renal vessels. Rare entities to be considered in differential diagnosis of patients presenting with lumbar flank pain and hematuria. AB - We report 2 cases of spontaneous thrombotic occlusion of the main renal vessels presenting with acute lumbar flank pain and hematuria suspect of nephrolithiasis. Clinical and laboratory signs of blood hypercoagulability, generalized arterial embolism, nephrotic syndrome or glomerulonephritis were absent. Excretory urography, nephrosonography and retrograde ureteropyelography showed no evidence of upper urinary tract calculi or other causes of obstruction. Renal angiography and cavography demonstrated an acute renal vein thrombosis in 1 patient and a thrombotic occlusion of all but one of the segmental renal arteries in the other patient. These 2 cases demonstrate that thrombotic occlusion of the renal artery or renal vein has to be considered in patients who are presenting with lumbar flank pain and hematuria, in whom the excretory urogram shows severe malfunction of one of the kidneys, and stone disease can be excluded. Renal angiography and cavography as well as CT scan should be carried out in these patients. When the disease is diagnosed at an early stage, an intra-arterial thrombolysis can be attempted. PMID- 1413312 TI - Renal cell carcinoma with unusual metastatic lesions detected by angiography. AB - The case of a patient with left renal cell carcinoma with two small metastatic lesions in the mesenterium and retroperitoneal fatty tissue is reported. These metastatic lesions were incidentally detected by preoperative routine angiographic examinations. The patient underwent left radical nephrectomy and resection of the metastatic nodules. The usefulness of angiography for detecting metastatic lesions and the possible metastatic pathways of these uncommon lesions are discussed. PMID- 1413313 TI - Coexisting renal cell carcinoma and xanthogranulomatous pyelonephritis in a chronic calculous disease. AB - Association of renal cell carcinoma (RCC) with renal calculi is very rare. Herein we report a case of RCC developing in a non-functioning kidney containing multiple renal and ureteric calculi. Histologically, the kidney, in addition, revealed changes of xanthogranulomatous pyelonephritis (XGP). XGP can be confused clinically, grossly and microscopically with RCC. In the present case both were coexistent and thus make it interesting. PMID- 1413314 TI - Focal xanthogranulomatous pyelonephritis: diagnostic and therapeutic aspects. AB - The authors report 2 cases of localized xanthogranulomatous pyelonephritis (XGP) in which computed tomography (CT) permitted to raise a motivated clinical suspicion of inflammatory disease: the surgical exploration documented absence of neoplasm and allowed a conservative therapy implying only the removal of the mass. A literature review confirms that some CT signs in XGP permit differentiation from carcinoma. If they are present, in unifocal cases of disease, the authors suggest a limited surgical approach and a therapeutic strategy as conservative as possible. PMID- 1413315 TI - Bellini duct carcinoma of the kidney. AB - We report a very rare case of Bellini duct carcinoma originating from the collecting tubules of the kidney. A left renal tumor was detected during a health examination and radical nephrectomy was performed. Histological examination showed papillary adenocarcinoma. By means of immunohistochemical methods, we felt that the tumor was a renal carcinoma of Bellini duct origin. PMID- 1413317 TI - Flap valve ureteral stent with an antireflux function: a review of 46 cases. AB - During a 2-year period, 46 patients with upper urinary obstructions (intrinsic obstruction and extrinsic compression) underwent treatment with a flap valve indwelling double-pigtail stent. Our subsequent analysis suggests that a flap valve at the lower end of a conventional ureteral stent can effectively prevent reflux in the upper urinary tract, and reduce discomfort and pain in the flank region during micturition. PMID- 1413316 TI - Gynecomastia and ectopic human chorionic gonadotropin production by transitional cell carcinoma of the bladder. AB - We report a patient with gynecomastia and ectopic production of human chorionic gonadotropin (HCG) by a transitional cell carcinoma of the bladder. In the present case, serum HCG levels and gynecomastia paralleled the clinical course. On admission, the patient was suffering from invasive transitional cell carcinoma (grade 3) of the bladder with metastasis to the left inguinal lymph nodes, together with gynecomastia. The serum HCG level was also elevated. After anticancer chemotherapy, the apparent bladder lesion and gynecomastia disappeared, and the serum HCG level declined to within normal limits. About 2 months after discharge, when the patient suffered from recurrent invasive tumors of the bladder, gynecomastia reappeared and the serum HCG level again became elevated. beta-HCG was demonstrated in biopsy tissue using the immunoperoxidase technique. The presence of beta-HCG was always focally demonstrated and was shown to be localized in the cytoplasm of the tumor cells. PMID- 1413318 TI - Secondary tumors of testis: two rare cases and review of the literature. AB - Secondary testicular tumor is a rare event. Approximately 200 cases have been documented in the international literature since 1935. The most common primary tumor sites have been the prostate, lung and kidney with other sites being reported less frequently. Our literature review discovered only 7 cases originating from primary tumors of the stomach and 14 cases from primary tumors of the colon. We want to add 2 more cases and discuss the possible mechanism of this neoplastic dissemination. PMID- 1413319 TI - Implantation of the urethral stent for treatment of complex urethral strictures. PMID- 1413320 TI - Significance of cavernosography in standardized cavernosometry. AB - Ninety-five patients with erectile dysfunction underwent standardized cavernosometry and cavernosography. In a first stage, the investigation was performed in each patient without and in a second stage with 60 mg papaverine injected intracavernously. A pathological maintenance flow rate between 20 and 120 ml/min decreased by 55% on average. The induction flow is of considerable variability and of poor diagnostic value. For quantification of venous leakage, the maintenance flow rate is of great importance and in correlation with the time of pressure decrease. Our results with a sensitivity of 59% suggest that cavernosography as the only screening method for venous leakage is not sufficient. In most of the cases, cavernosography is indicated only in consideration of venous leakage surgery. PMID- 1413321 TI - Surgical approach of venous leakage. AB - Venous leakage is a cause of impotence easily demonstrated by dynamic cavernosography. It revealed dorsal venous leakage in 41 patients, perineal leakage in 15 patients and dorsal plus perineal leakage in 42 patients. Dorsal vein ligation was performed in 38 cases. Fourteen patients underwent ligation of crura penis. Combined procedure was done in 36 patients. Immediate results of the surgical approach are quite encouraging, but finally, they are satisfactory in only 20% of the cases. Nevertheless, surgical treatment of venous leakage can further be taken into consideration to reduce blood outflow and strengthen vasoactive drug effects. PMID- 1413322 TI - Venous surgery in veno-occlusive dysfunction: long-time results after deep dorsal vein resection. AB - Follow-up of patients 1 year after deep dorsal vein resection gives evidence of an approximate 50-60% success rate. A careful selection of only this small percentage of patients, in whom abnormal drainage through the penile dorsum is obvious, is mandatory. Men with an arterial cofactor have to be excluded or to be subsequently treated by intracavernosal autoinjection of vasoactive substances. Late results from our study demonstrate a further loss of sufficient erection, also in men considered as persistent success by us, in the subjective view of the patient and/or his sexual partner. PMID- 1413323 TI - Venous surgery in erectile dysfunction. AB - According to the physiopathological process beyond it, veno-occlusive dysfunction (VOD) may be classified in organic or functional VOD. The former is caused by lack of control of smooth muscle relaxation, while the later is related with morphological alterations of the corporeal tissue. The differential diagnosis of those two types is fundamental when venous surgery is to be discussed. Functional VOD may be treated with sex therapy, while in organic VOD, surgical treatment may be considered. The experience with venous surgery for impotence at the H. Ellis Institute was not encouraging. Although a few patients were cured, the long-term follow-up showed that only 9 out of 57 patients were able to have a normal sexual life. New diagnostic tools, as well as a better understanding of the erectile mechanism, may lead to a better selection of cases with an improvement of the results in the future. Today, venous surgery remains as an option to patients with organic VOD, who are willing to accept a 45% probability of improvement for a few months, having been informed about all the other options in the treatment of erectile disorders. PMID- 1413324 TI - Penile venous ligation surgery for the management of cavernosal venous leakage. AB - Forty-one patients underwent penile venous ligation surgery for pure cavernosal venous leakage diagnosed by infusion cavernosometry and cavernosography. Before surgery, arterial integrity was assessed by pelvic angiography, and all patients were found to have a normal penile arterial system. The patients were divided into two groups on the basis of the type of venous operation performed. The overall complete-potency success rate was 46% (19 of 41 patients). Postoperative complications were minimal. Our experience shows that penile venous surgery remains an acceptable option for treatment of carefully selected patients with documented pure cavernosal venous leakage of a mild degree who have no evidence of arterial insufficiency and who do not prefer, or are not suitable for, other medical or surgical treatment options. Patients who had more severe degrees of cavernosal venous leakage had a poor result from this procedure. For patients with moderate to severe venous leakage, we now perform a combined surgical procedure, deep dorsal vein arterialization and venous ligation. PMID- 1413325 TI - Venous surgery in erectile dysfunction. The role of dorsal-penile-vein ligation and spongiosolysis for impotence. AB - We report here on our surgical experience with venous leakage of the cavernous bodies. Out of 159 patients operated on, 134 were available for long-term follow up. Depending on the cavernosographic findings, one of three different surgical procedures was carried out: ligation of the deep dorsal vein of the penis, spongiosolysis, or ligation of the crura. 18% of the patients undergoing ligation of the deep dorsal vein, postoperatively attained spontaneous erections, while 35% needed adjuvant corpus cavernosum autoinjection therapy. Spongiosolysis gave a more favourable result: spontaneous erections in 30% and vasoactive drug dependent erections in 35%. Crural ligation did not prove successful. No serious complications were encountered postoperatively. Our data suggest that venous surgery should only be offered to a selected group of patients comprising young impotent men with venous leakage, maybe in combination with arterial disease, and patients suffering from distal venous leakage. Old age, neurogenic disorders causing erectile dysfunction, and diabetes mellitus should represent exclusion criteria for venous surgery. PMID- 1413326 TI - Management of corporal veno-occlusive dysfunction. AB - Veno-occlusive dysfunction has become a recognized cause of organic impotence. The existence of concomitant arterial and sinus smooth-muscle disease makes this disorder often difficult to diagnose. It rarely can be the sole etiology for impotence. The authors' experience in the treatment of this disorder in over 100 patients is presented. The authors rely on cavernosometry/pharmacocavernosometry/pharmacocavernosogr aphy and the color duplex Doppler screening test (to eliminate concomitant arterial disease) as the primary diagnostic tools. Twenty-two patients of 58 (38%) have achieved long lasting success from the surgery so that they are able to have vaginal intercourse. Another 12 patients (21%) have been improved but must depend upon pharmacological injection therapy to obtain a sufficient erection for intercourse. There has been a 41% failure rate, and these are discussed. PMID- 1413327 TI - Venous leakage--a new therapeutical concept. AB - According to our opinion, so-called venous leakage is no venous disease but a result of impaired cavernous tissue. Since in over 90% of all patients with venous leakage also arterial disease was discovered and since ultrastructural degenerative processes in the cavernous bodies were detected, we consider traditional corrective venous surgery as unphysiological and illogical. We suggest arterial revascularization combined with a mechanical penis banding as a new therapeutical concept. PMID- 1413329 TI - Venous leakage. PMID- 1413330 TI - Organic erectile dysfunction appears to occur frequently as a consequence of abnormal corporal veno-occlusive hemodynamics. PMID- 1413328 TI - Venous surgery in erectile dysfunction: therapeutic strategy and results. AB - The therapeutic rationale of venous surgery is to create an effective obstacle to the pathologically increased venous outflow, determined by an intrinsic pathology of the cavernous bodies. In the last 15 years, many techniques have been proposed, and our therapeutic approach has evolved with our knowledge of penile haemodynamics. Up to October 1990, we performed 316 operations for the relief of impotence. In a 2-year follow-up our recurrence rates were as follows: DDV plus corporpexy (n = 50): 26% (n = 13); DDV plus crura plication (n = 34): 47% (n = 16); DDV plus collateral vein ligation (n = 48): 62.5% (n = 30). PMID- 1413331 TI - Present state of diagnostic management in veno-occlusive dysfunction. AB - Pharmacocavernosometry and pharmacocavernosography are essential for the diagnosis of veno-occlusive dysfunction. Pressure fading obtained by cavernosometry correlates excellently with results of intracavernosal pharmacon testing. Venous drainage as visualized by pharmacocavernosography is essential for localization of the venous channels especially if venocorrective surgery is planned. PMID- 1413332 TI - [The cardiovascular and thromboembolic complications of intravital estrogen therapy in middle-aged and elderly patients with prostatic cancer]. AB - Cardiovascular and thromboembolic complications arising as a result of 1-16-year estrogen therapy were evaluated in 105 prostatic cancer patients. The incidence of the complications was higher in those who had pretreatment cardiological or vascular load. The latter caused death in half of the patients. Preventive and therapeutic measures to control the complications, prognosis signs are indicated. PMID- 1413333 TI - [The prognosis of the treatment results in patients with operable kidney cancer]. AB - Computer processing by 73 characteristics in the system "host-tumor" was performed for 322 patients operated on for renal carcinoma from 1976 to 1986. The automatic classification method or cluster-analysis allowed distribution of the patients into homogeneous preoperative and postoperative groups (classes) which differed by the mean of the signs in the classes, survival and response to treatment. The formulas have been derived that enable the clinicians to refer the patients to a certain prognostic group without using a computer. This suggests more grounded examinations and treatment policy. PMID- 1413334 TI - [The role of transperitoneal fine-needle aspiration biopsy in the diagnosis of obstructive uropathy in patients with cervix uteri cancer]. AB - Upon the exposure to remote or combined radiotherapy, the patients with uterine cervical cancer often develop ureterostenosis due to recurrence or postradiation alterations in the walls and adjacent tissues of the ureter. Etiology of the urodynamic defect is essential for the treatment policy choice. Therefore, in attempt to find out effective means of differential diagnosis between ureteral obstruction due to cervical cancer relapse and due to postradiation lesion, the authors tried transperitoneal aspiration biopsy with thin needle as a tool of such diagnosis. The biopsy was obtained from 19 females. In 14 of them the obstruction was attributed to recurrent cancer, in 5 to radiotherapy. No errors in the diagnosis were made. Thus, the accuracy of the method reached 100%. PMID- 1413335 TI - [The functional assessment of the renal parenchyma and perirenal fatty tissue during electropiezolithotripsy by x-ray computed tomography]. AB - Computed tomography was performed before and after telelithotripsy to evaluate changes in renal parenchyma induced by the procedure in 34 patients with nephroliths. Piezolith-2300 lithotriptor ("Wolf", FRG) was employed. The images showed no serious parenchymal injuries or paranephric hematomas, on the one hand, but density changes in the parenchyma, on the other hand. These were of 3 types: focal reduction in 3, diffuse reduction in 4 and diffuse increase of the density in 2 patients. As shown by comparison with literature data, telelithotripsy on "Piezolith-2300" causes minimal changes in renal parenchyma and perirenal fat. In view of this, the procedure is recommended for wide clinical and outpatient practice. PMID- 1413336 TI - [Telelithotripsy in the treatment of staghorn nephrolithiasis in children using the URAT-P lithotriptor]. AB - The paper presents the results of telelithotripsy monotherapy for 34 staghorn stones in 32 nephrolithiasis children carried out at the RSFSR Research Institute of Urology, Moscow. Commonest manifestations of the disease were leukocyturia (87.5% of cases) and Proteus bacteriuria (31.8% of cases). Basing on roentgenological findings, the stones were classified into 3 groups: initial (K1), incomplete (K2) and complete (K3). All the children underwent treatment on Soviet lithotriptor "URAT-P" under a delicate regime using different techniques of disintegration which started from the periphery and advanced to the pelvic part of the calculus. No pretreatment drainage of the pelvicaliceal system was performed. The intended staged disintegration of the stones was achieved in 94.2% of cases at 2.4 sessions, on the average, and overall number of impulses 1973.1 per each stone. At discharge 76.4% of the children were free of the main mass of the stone dust. Acute pyelonephritis which appeared the most frequent postoperative complication developed in 7.8% of the patients one of which required open nephrostomy and one percutaneous puncture nephrostomy. Other cases were treated by specific antimicrobial therapy. Complete series of investigations in the postoperative period did not reveal any intra- or pararenal hematomas. Radioisotopic renography revealed improvement in renal function in 62% of cases in early postoperative follow-up. Thus, 93.8% of children with stag-horn stones were spared of traumatic operative intervention or invasive manipulations. This makes the method of telelithotripsy a valuable therapeutic tool in childhood staghorn nephrolithiasis. PMID- 1413337 TI - [Extensive operations in kidney cancer complicated by tumor thrombus invasion of the inferior vena cava]. AB - Invasion of renal tumor into retroperitoneal major vessels with thrombosis should be characterized as local spread of renal carcinoma and a serious complication. Extensive interventions were conducted in 30 subjects out of 196 nephrectomy cases. Nephrectomy was attended by colectomy (3 cases), pancreatic resection and adrenalectomy (3 cases), resection of the liver (2 cases), one-stage lobectomy (2 cases), adrenalectomy (9 cases), resection of the uterine appendages (1 case), resection of the colon, splenectomy, opening of an intraorganic abscess. 12 patients underwent thrombectomy from the major vein via the thoracophrenoabdominal approach. Cavathrombectomy was carried out in 7 (3.6%) patients, in 3 of which vena cava inferior was resected. Removal of the thrombus from the renal vein with resection of the opening and suturing of the vena cava inferior was performed in 5 patients. The thrombus originated from the right kidney in 9, while from the left one in 3 patients treated surgically. The thrombi occupied 4-10 cm along the renal vein from its opening. The removed kidney weighted from 400 to 3200 g. One death occurred due to pulmonary embolism during the operation, one on day 5 due to cardiopulmonary insufficiency. Histological examinations of the thrombi showed them to consist of fibrin, blood elements and tumor cells within the thrombus. The thrombi grow slowly, undergo organization and vascularization. Tumor cells multiply in the thrombus. Fibrin coating restricts cancer cell free dissemination via the venous system. Cavathrombectomy is considered the only way to prolong survival for the above patients. PMID- 1413338 TI - [The removal of calculi from the pelvic ureter by extracorporeal lithotripsy]. AB - Using high-energy impulses from Dornier HM-3 lithotriptor, iliac ureteroliths were crushed in 18 patients for the period of 2.5 years. The mean age of the patients was 38 years. The lithotripsy was in all cases preceded by retrograde catheterization. Reposition of the stones was achieved in 6 patients. Prone position lithotripsy was conducted in 12 patients. Specially designed support cushions helped to keep the patient in a steady position, speeded up the stones excretion, relaxed knee joints and reduced the exposure to the impulses. All the patients underwent antiinflammatory and spasmolytic therapy. The mean hospital stay reached 3.2 days. Good results were reported in 94.1% of those treated. Neither early nor long-term complications arose. PMID- 1413339 TI - [The rehabilitation of patients with urethral injuries and their sequelae]. AB - The treatment was conducted for 154 patients aged 3-69 with traumatic rupture of the urethra. Eighteen patients underwent primary suturing, five patients primary delayed repair of the urethra. Urethral patency was achieved in all the cases. In 127 cases urethral rupture was associated with visceral and skeletal injuries managed by epicystostomy with good results. 16 patients without extended diastasis of the urethral fragments got circular tubes. 24 patients out of 111 developed restenosis (7 due to urethrotomy and 17 after tunneling). Later on 14 of these and the rest 87 patients were subjected to plastic reconstruction. Out of 101 patients operated on 3 needed bougienage, 1 patients retained urethrorectal fistula. 8 patients had postoperative dynamic urethral obstruction removed upon augmentation of detrusor tonicity by means of intravenous administration of calcium chloride and strofantina. Copulative dysfunction occurred in 70% of the patients over 22 years of age. Extracavernous prosthetic implantations performed in 33 of them corrected erectile impotence [correction of importance]. PMID- 1413340 TI - [The characteristics of the membranous part of the urethra]. AB - The membranous part of the urethra has anatomic specificity influencing its trauma mechanism and allowed for in the trauma treatment policy. In 239 patients with an injured membranous part of the urethra described in the paper, the rupture was mainly due to the hip fracture. 85% of the patients developed a complete rupture with subsequent obliteration, 15% had strictures. Cicatrization involved the whole membranous part in 74% of the cases. In relevant traumas common are severe rectourethral and peritoneal fistulas surgical treatment of which as well as obliterations involves great technical difficulties. There is a variety of operative approaches and techniques (perineal, original anteropubic and anorectal). Urethral reconstruction should not be followed by bougienage. Typical are also frequent renal and genital complications (phlegmons, nephroliths, ureteroliths, epididymitis, orchitis, prostatitis, pyelonephritis). The number of complications depends on the choice of the adequate operative technique and due consideration of anatomical characteristics of the membranous part of the urethra. PMID- 1413341 TI - [Treatment results in urethral strictures]. AB - A total of 231 patients with urethral strictures were treated. The disease resulted from trauma, adenomectomy, chronic urethritis, prostatic sclerosis in 92, 72, 51 and 16 patients, respectively. Fifty-one patients underwent conservative treatment which involved bougienage, resolving and anti-inflammatory agents. 38 of them responded, 13 nonresponders were operated on. 72 patients were subjected to partial urethral tunneling according to an original technique which brought success in 90% of the cases. Out of 92 traumatic urethral strictures 88 were cured after end-to-end plastic reconstruction. It is believed that urethral strictures should be managed individually basing on the stricture cause, location, length, severity, complications. PMID- 1413342 TI - [The surgical treatment of posttraumatic urethral strictures]. PMID- 1413343 TI - [An improved guide for urethral bougies]. AB - A routine-technique urethral bougienage using an elastic guide in marked urethral strictures is performed practically at random in view of great difficulties of the guide advance through the narrow part of the urethra which is not safe for urethral tissues. An atraumatic guide developed by the authors is radio-opaque. This makes it possible to bring it along the urethra to the bladder under the control of x-ray television and to avoid damage to the tissues. The guide was used in 9 patients with urethral strictures who failed bougienage attempted by conventional methods. Not only the results were positive, but also there were no complications such as urethrorrhagia, false urethral passages and urethral fever. PMID- 1413344 TI - [A way to improve the quality of compression anastomoses of the urethra in children]. AB - The paper presents the analysis of compression anastomosis establishment in surgical treatment of children with posttraumatic strictures of the posterior urethra. It is noticed that quality of the anastomoses deteriorates with enlargement of the interpolated tissues layer. Anastomosis is suggested to be formed between submucous layers. The new variant was tried in experiment on 9 dogs and in 5 patients with posttraumatic urethral strictures. As a result of more advanced anastomoses the thickness of the interpolated tissues reduced 2-3 fold. The techniques of the above surgery are discussed as well as the advantages of the proposed submucous compression anastomosis in posttraumatic strictures of the posterior urethra. PMID- 1413345 TI - [The assessment of the state of the blood lipid spectrum, hemostasis, hormonal homeostasis and hemodynamics in the early diagnosis and drug correction of the cardiovascular changes in prostatic cancer patients undergoing estrogen therapy]. AB - A complex of investigation was performed in 30 males with newly diagnosed prostatic cancer (stages T2NOMO-T3NO-1MO) before treatment with estrogens, 2-3 months and 1 year after its start. The complex included evaluation of blood lipid spectrum (HDL, LDL, VLDL, triglycerides), hemostasis (coagulation, platelet aggregation, fibrinolysis), hormonal profile (blood hydrocortisone, aldosterone, testosterone, estradiol, STH, FSH, LH, prolactin, plasma renin activity), central and intracardiac hemodynamics, ECG. 66 healthy men of advanced age served control. It was found that estrogen therapy affected blood lipid metabolism, leading to impairment of physiological correlation between HDL and triglycerides, increased blood levels of VLDL and triglycerides. Long-term estrogen treatment brought about enhancement of hemocoagulation and platelet aggregation. Hormonal shifts involved hyperprolactinemia, hypersomatotropism, hypercorticism, aldosterone hypersecretion, proportional androgens-estrogens alterations. Hormonal abnormalities produce side effects in estrogen-treated CHD and hypertonic patients: negative ECG readings indicative of deteriorated coronary circulation and hypertensive episodes, central hemodynamic disorders, respectively. In view of possible cardiovascular damage related to estrogen therapy, a differentiated approach is proposed which would allow a long-term estrogen treatment free of relevant complications. PMID- 1413346 TI - Current diagnosis and treatment of urinary tract infections. PMID- 1413347 TI - Technique of external sphincter balloon dilatation. AB - We report on our technique and early experience with balloon dilatation of the external sphincter in 7 spinal cord-injured men with detrusor external sphincter dyssynergia and elevated voiding pressure. Following dilatation, bladder emptying into condom catheters was achieved in all patients without dribbling incontinence. PMID- 1413348 TI - Technical aids in investigation and management of urethral diverticula in the female. AB - Three aids in the diagnosis and management of urethral diverticula are described. First, the technique of double-balloon urethrography has been modified. Diluted contrast medium is used to inflate the intravesical and external balloons so that improved delineation of the anatomy of the diverticular pouches is obtained with undiluted contrast medium. Second, for identification and irrigation with antibiotic solution of the nondraining pouches of compound diverticula, an angiographic catheter is placed in the most distal pouch using fluoroscopically guided manipulation, and then this catheter is replaced with a pigtail-shaped nephrostomy drainage catheter. Third, a 7 F Foley catheter balloon is placed in thin-walled and friable diverticular pouches to facilitate dissection. PMID- 1413349 TI - Prototype of a reflux-preventing ureteral stent and its clinical use. AB - We have experimentally produced a ureteral stent which prevents vesicorenal reflux. This stent has a thin silicon sleeve at its distal end (intravesical portion). In a model experiment the sleeve demonstrated an excellent capability to prevent reflux. The sleeve allowed flow of fluid with minimal pressure rise. A patient with bilateral ureteral obstruction was managed with endoscopic insertion of a sleeved stent in the right ureter and a usual pigtail stent in left ureter. During cystography vesicorenal reflux was not observed on the right side while reflux occurred on the left side. Excretory urography forty days after stent placement demonstrated recovery of renal function and maintenance of drainage in both renal units. Thus, the drainage characteristic of this stent appears to be approximately the same as that of usual stent. PMID- 1413350 TI - KTP-532 laser ablation of urethral strictures. AB - In 1988 the KTP-532 laser was used to ablate a series of benign urethral strictures. Rather than using a single incision as in urethrotomy, strictures were treated with 360-degree contact photoradiation. Thirty-one male patients, average age 53.2 years, received thirty-seven treatments; 6 patients underwent a second laser treatment. Stricture etiology was commonly iatrogenic (32%), traumatic (16%), and postgonococcal (10%). Stricture location included mainly bulbar (49%), membranous (20%), and penile (12%) areas. The surgical technique consisted of circumferential ablation, followed by Foley catheter placement (mean, 10 days). Follow-up on 29 of 31 patients ranged from one to sixteen months (mean 9.7). Complete success occurred in 17 patients (59%) who had no further symptoms or instrumentation. Partial success was seen in 6 patients (20.5%) with symptom, but not stricture, recurrence. Six patients (20.5%) failed therapy, requiring additional surgery or regular dilations. No complications were seen. Although longer assessment is required, KTP-532 laser ablation of urethral strictures appears efficacious. PMID- 1413351 TI - Identification of motile sperm in caput epididymis. Intraoperative observations and clinical correlations. AB - This retrospective review of patients who underwent vasoepididymostomy demonstrates that motile sperm may be identified in the most proximal portion of the epididymis, and implies that induction of sperm motility may be independent of transit through the epididymis. Although further studies are needed, the data imply that it may not be necessary to identify motile sperm in the epididymal fluid to achieve a successful vasoepididymostomy. PMID- 1413352 TI - Vesicoureteral reflux in children with and without a history of urinary tract infection: a comparative analysis. AB - Eighty-eight children who were discovered to have vesicoureteral reflux were prospectively studied over a two-year period. Two groups were compared: 49 who presented with a urinary tract infection and 39 who were identified through prospective screening. Based on the distribution of grade and the presence of parenchymal scarring, the severity of vesicoureteral reflux was comparable in the two groups. Of note, more males with reflux were identified in the noninfected group, whereas sex distribution was almost equal in the infected group. Ultrasound alone was found to be highly inaccurate in identifying reflux or parenchymal changes. In conclusion, screening of at-risk groups of children without a history of urinary tract infection may identify patients with clinically significant vesicoureteral reflux. PMID- 1413353 TI - Accessory and ectopic scrotum with VATER association. AB - Scrotal ectopia or accessory scrotum are both rare conditions. This report describes a neonate with both abnormalities, who also has elements of the VATER association. This constellation of anomalies has not been previously described. PMID- 1413354 TI - Preoperative assessment of prostatic carcinoma by computerized tomography. Weaknesses and new perspectives. AB - A retrospective study of five years' experience with fourth-generation computerized tomography (CT) scan was undertaken to assess the frequency of understaging in prostate cancer. A total of 160 patients with preoperative scans were surgically staged. In 10 patients, the operation was aborted after pelvic node dissection had revealed unsuspected metastatic involvement. Based on the histopathologic evidence of local tumor invasion, extension into seminal vesicles or pelvic lymph nodes, restaging was required in 78 percent of cases. Accuracy was 24 percent for capsular extension, 69 percent for seminal vesicle invasion, and 72 percent for lymphadenopathy. The poor yield of CT scan as a preoperative staging modality is demonstrated. Recent advances in the understanding and management of prostatic cancer require reassessing patient benefit and cost effectiveness of available imaging techniques, focusing on the problem of detecting nodal metastases, and predicting tumor spread to regional lymph nodes by accurately evaluating the primary neoplasm. We conclude that CT scan fails to demonstrate the required precision needed to evaluate local tumor spread; therefore, this goal must be pursued with newer imaging modalities. PMID- 1413355 TI - Is magnetic resonance imaging alone accurate enough in staging renal cell carcinoma? AB - A patient with renal cell carcinoma extending into the inferior vena cava presented to our institution. Magnetic resonance imaging demonstrated the superior extent of the thrombus to be at the level of the hepatic veins. Preoperative venacavography showed extension into the right atrium. The need for both studies in evaluating patients with Stage 3A disease is reviewed. PMID- 1413356 TI - Unusual presentation of renal oncocytoma. PMID- 1413357 TI - A new, efficient table-drain assembly for endoscopic surgery. PMID- 1413358 TI - Adenomatoid tumor of testicle. AB - A rare case of intratesticular adenomatoid tumor is described. Pathologically and clinically this tumor is associated with the seminiferous tubules and the rete testis. The patient underwent left inguinal exploration to confirm the testicular tumor. A radical orchiectomy was performed. We believe this is the first case of documented intratesticular adenomatoid tumor that did not arise from either tunica albuginea or epididymis. The cytologic origin of adenomatoid tumors and an unusual finding of decreased spermatogenesis with marked atrophy of the testes are also presented. PMID- 1413359 TI - Ureteropelvic junction obstruction caused by accessory renal vessels in association with preureteral vena cava and vena caval duplication. AB - An apparent ureteropelvic junction obstruction on the right side may herald an array of anomalous conditions for which the surgeon should be prepared. A case is presented in which ureteropelvic junction obstruction caused by accessory renal vessels was found in association with a preureteral vena cava and a vena caval duplication on the right side. The embryology of caval anomalies associated with preureteric vena cava is reviewed. PMID- 1413360 TI - Testicular teratocarcinoma with intracaval metastases to the heart. AB - We report a case of testicular teratocarcinoma involving the inferior vena cava with extension to the right atrium and metastases to the tricuspid valve. We believe this to be the first such reported case. PMID- 1413361 TI - Priapism associated with asplenic state. AB - Priapism may be primary (idiopathic) or secondary to sickle cell anemia, trauma, leukemia, drugs, venous thromboembolic diseases, and other less common disorders. This study concerns 21 patients with priapism treated during a period of ten years. Nine patients (43%) had sickle cell anemia. Of the 12 individuals (57%) classified as idiopathic, 3 (25%) had previously undergone surgical splenectomy for benign conditions. Considering the propensity for this unusual condition to develop in patients with hemoglobinopathy-induced hyposplenism, the possibility of a relationship between the asplenic state and priapism is considered. PMID- 1413362 TI - Use of tunica vaginalis patch graft for repair of traumatic testicular rupture. AB - Early exploration of patients with testicular rupture has become the standard of care in traumatic testicular injuries. We report on a case of traumatic rupture of the testicle diagnosed by ultrasonography, with a large testicular defect that could not be closed primarily. This was managed successfully with a free graft of tunica vaginalis. The affected testicle is palpably normal three months postoperatively. This technique may represent a valuable adjunct in managing major testicular ruptures. PMID- 1413363 TI - Sarcomatoid renal carcinoma with angiosarcomatoid component. Light microscopic and immunohistochemical study. AB - We describe a case of primary renal pelvic carcinoma which showed an unusual histologic pattern of anastomosing blood-filled channels lined by atypical cells. This angiosarcomatoid pattern merged with solid areas typical of renal carcinoma. Immunoperoxidase stains for cytokeratin and epithelial membrane antigen were positive in both the angiosarcomatoid and typical carcinomatous areas, while stains for factor VIII-related antigen and desmin were negative. Since primary renal angiosarcomas are rare neoplasms, the diagnosis of sarcomatoid renal carcinoma should be considered in primary renal neoplasms which show this angiosarcomatoid pattern. PMID- 1413365 TI - William Bosworth Castle. PMID- 1413364 TI - Anatomic, functional, and pathologic changes from internal ureteral stent placement. AB - The anatomic, hydrodynamic, functional, and pathologic changes associated with unilateral internal ureteral stenting were evaluated in 20 female canines. Selective glomerular filtration rates (GFR) were measured with technetium 99m diethylenetriamine pentaacetic acid (DTPA) renal scans (N = 14) prior to and several weeks after unilateral internal stent placement. Cystometry and cystography were done at weekly intervals to determine if reflux occurred and to measure the intravesical pressure to produce this reflux (N = 16). Ureteral lumenal capacities of mid 6-cm ureteral segments of stented and unstented ureters were compared. The mid-ureteral lumenal volumes were three times greater in the stented ureters (p < 0.002). There were no significant differences in the selective GFR before and after stenting. Low-pressure vesicoureteral reflux occurred at a mean intravesical pressure of 13.7 cm of water and was present in 84.6 percent (11/13) of the canines whose stents did not migrate or obstruct from encrustation. There were no significant alterations in serum chemistries or blood counts. Fluoroscopic imaging also showed ineffective ureteral peristalsis. This study confirms that internal ureteral stents cause vesicoureteral reflux and significant lumenal dilation without altering renal function. PMID- 1413366 TI - Walter Murray Kirkendall. PMID- 1413367 TI - Francis Clark Wood. PMID- 1413368 TI - Frank P. Brooks. PMID- 1413369 TI - Pacesetters of the American image or (a case for a pleasant diversion). AB - Regardless of how you resolve the morality of our history, the fact is that Currier and Ives documented in their own special and often biased way the iconography of the growth and development of the United States of America (Fig. 88) in some of the most eventful years of its history from about 1840 through 1895. Now, as we near our 500th anniversary commemoration of Columbus' voyage to the Americas, it seems especially appropriate to review--to think about all of this. I think you have sensed, as we have gone along, that learning about Currier and his colleagues--these pacesetters of the American Image--has meant, as Osler predicted, a pleasant diversion for me. These activities have carried me into new areas of interest, expanding my perspective of the American Image--of people, of medicine, of life in general, and aiding in the identification of values, my own, as well as those of others. All along, my knowledge has been enhanced, especially of the history of this wonderful complex country of ours. Furthermore, and of considerable importance, this endeavor has sharpened my power of observation. I have, like a good doctor should do, learned to look better! PMID- 1413370 TI - The role of endothelial dysfunction to predict the development of allograft coronary artery disease following cardiac transplantation. PMID- 1413371 TI - The human prepro thyrotropin-releasing hormone (TRH) gene: cloning, characterization, hormonal regulation, and gene localization. PMID- 1413372 TI - Thyroid disease during pregnancy. PMID- 1413373 TI - An analysis of the medical problems of the Civil War. PMID- 1413374 TI - The Gordon Wilson Lecture. The ABC's of viral hepatitis. PMID- 1413375 TI - The natural history of primary biliary cirrhosis. PMID- 1413376 TI - Solving the puzzle of hormone-dependent breast cancer. PMID- 1413378 TI - The crisis in biomedical research funding. PMID- 1413377 TI - Marijuana use and the risk of new onset seizures. PMID- 1413379 TI - The crisis in biomedical research funding--a commentary. PMID- 1413380 TI - The Jeremiah Metzger Lecture. Microbial defenses against killing by phagocytes. AB - Phagocytes are a key feature of defense against microorganisms. Phagocyte function is a complex system with many intricately involved components. Each of these components provides microorganisms with a target for countermeasures against phagocytes. We have discussed examples and purported mechanisms for microbial defenses against the steps involved in killing by phagocytes. Understanding the interplay of these host and pathogen factors leads to a better understanding of both normal host defenses and pathogenesis of disease. PMID- 1413382 TI - Is asthma always an allergic disease? PMID- 1413381 TI - Plaque-associated immune reactivity as a tool for the diagnosis and treatment of atherosclerosis. AB - In summary, we have confirmed that a specific humoral immune reactivity involves human atherosclerotic plaque. By isolating some of the autoantigens and employing them in prototype immunoassays, we have been able to measure for the presence of plaque-specific antibodies. Extracted plaque antigens have also served as immunogens in monoclonal antibody generation. These have shown early promise as plaque-directed in vivo targeting agents. Further scientific evaluation and reagent development remains before the practical utility of employing such reagents or methods in the care of patients with atherosclerosis-related diseases can be ascertained. PMID- 1413385 TI - Evaluating medical technology in the 1990's. PMID- 1413384 TI - Human chorionic gonadotropin-like proteins: secretion in nonpregnant humans and production by bacteria. PMID- 1413383 TI - Autonomic dysfunction: diagnosis guided by therapy. PMID- 1413386 TI - The remarkable contributions of S. Burt Wolbach on rickettsial vasculitis updated. PMID- 1413387 TI - [The effect of Zindep on B-lymphocyte levels in pregnant cows]. AB - In the present study the immunomodulation effects of the Zindep preparation, based on elementary zinc and zinc oxide, were followed on the humoral response of gravid cows in the 8th and 9th months, a week after parturition and in calves immediately after parturition and on day 15 of their life. An increased level of B-lymphocytes was observed on days 2, 5, 8, 15, 30 and 50 of the experiment. The highest average values were recorded in the experimental group on days 8 and 15 of the experiment. The mentioned values were statistically significant (T-test) at the level 0.05 and 0.01. The average values of B-lymphocytes in cows after parturition reached 22.3% in the cows of the experimental group and 20.5% in the control group. No pronounced differences in the number of B-lymphocytes in the calves of both followed groups were recorded. The statistical evaluation of the values obtained in the cows after parturition as well as in the calves was not carried out due to a small number of samplings. PMID- 1413388 TI - [The characteristics and regulation of glutamate dehydrogenase in strains of Bacteroides ruminicola ssp. ruminicola isolated from the rumen of fallow deer]. AB - Very little information about NH4+ assimilation paths in rumen anaerobic bacteria is available, and the information about wild animals is completely missing. Glutamate dehydrogenase (GDH) isolated from the rumen strain B. ruminicola in fallow deer was purified and its properties were specified after crystalline ammonium sulphate precipitation and gel filtration on Sephadex G-200. The properties of partly purified GDH were specified. One of the first specifications concerning GDH from various sources was to determine its coenzyme specificity. The results of these determinations enabled to draw a general conclusion that GDH from non-animal sources was specific to only one coenzyme while GDH from animal sources could utilize the two coenzymes (Frieden, 1964). In our study the specificity of GDH isolated from the rumen strain B. ruminicola in fallow deer to the coenzyme NADH (Tab. I) was determined; this specificity was different from the coenzyme specificity of GDH isolated from the rumen strain B. ruminicola in calves where GDH was found to be specific to the coenzyme NADPH. The effect of increasing concentrations of NADH, 2-oxoglutarate and NH4+ on the enzyme reaction velocity was also investigated and Km was determined for NADH, 2-oxoglutarate and NH4+ (Tab. II). The kinetic properties of GDH isolated from different sources are considerably variable. Michaelis constants for GDH range from 0.003 to 0.125 mmol/dm3 for NADPH (NADH), from 0.95 to 7.4 mmol/dm3 for 2-oxoglutarate, and from 0.25 to 16 mmol/dm3 for NH4+ (Misono et al., 1985). The average value of Km for NH4+ in a mixed rumen population was 33 mmol/dm3 (Erfle et al., 1977).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413389 TI - [A practical immunologic skin test for piglets]. AB - At present immune system performance in pigs is decreasing, particularly as a result of environment quality deterioration. Immunological skin tests can also be used to determine the degree of immune system impairment in piglets. A practical immunological skin test was carried out in 48 weaned piglets with the body weight of 15-30 kg. The test was located on the piglets' backs after bristles had been shaved off. The test consists in intradermal injections of a physiological saline (900 micrograms NaCl in 0.1 ml), histamine (100 micrograms in 0.1 ml) and phytohaemagglutinin (0.1 ml; Institute of Sera and Vaccines, Praha). The size of the papule (in 20 minutes) and the size of the induration (in 24 hours) were measured in two perpendicular directions, and the mean value (in mm) was calculated from the measured data. In 20 minutes the average size of the papule was 9.4 mm after the application of the physiological saline and 20.5 mm after histamine application (Fig. 1). In 24 hours after phytohaemagglutinin application the average size of the induration was 15.9 mm (Fig. 2). In twenty minutes the increased reaction to histamine (the papule larger than 24 mm) was observed in four piglets (8.3%); these piglets show the predisposition to allergic diseases (Fig. 3). In another four piglets (8.3%) the decreased reaction to phytohaemagglutinin (endurance of 13 mm and less) was observed in 24 hours; these are piglets with the decreased cellular immunity (Fig. 4). The increased reaction to histamine and the decreased reaction to phytohaemagglutinin were found only in one (2.1%). Piglets with abnormal dermal reaction can represent the risky part of the pig subpopulation which adapt themselves less easily to the stress on large pig farms. A veterinary surgeon and his assistant can examine by this test 20 piglets in the herd. This skin test was recommended as a practical cheap screening test for use in pig herds to evaluate preliminarily the predisposition to allergic diseases and cellular immunity of piglets. PMID- 1413390 TI - [The effect of defaunation on fermentation in vitro]. AB - An experiment was conducted to investigate the effects of defaunation on the fermentation of two different diets consisting of hay (100%) and hay+barley (80% + +20%) in a rumen pouch (RUSITEC). The survival and composition of protozoa were investigated in an in vitro system in control vessels where no defaunation was carried out. Defaunation decreased the production of total volatile fatty acids (P < < 0.01), acetate, butyrate (P < 0.001)--Tab. II; dry matter digestibility (P < 0.05) and detergent fibre digestibility: acid detergent fibre (ADF), neutral detergent fibre (NDF), cellulose (P < 0.001), hemicellulose (P < 0.01 and P < 0.001, respectively) in our experiment (Tab. I). These parameters also decreased: production of CH4 (P < 0.001), CO2 (P < 0.01 for the barley diet), total production of gases (P < 0.001 for the barley diet), total utilization (P < 0.01 and P < 0.001, respectively) and recovery of H2 (P < 0.05 and P < 0.001, respectively), NH3-N in effluent (P < 0.001 and P < 0.01, respectively)--Tab. III; and production of ATP (P < 0.01)--Tab. IV, as a result of fermentation in our experiment. On the other hand, there was a significant increase in the following parameters: production of propionate (P < 0.001 for the barley diet)- Tab. II; microbial nitrogen/kg of organic matter fermented--OMF (P < 0.001), Tab. III; energy yield--E of volatile fatty acids (VFA), proportion of VFA energy with respect to fermented hexose energy--E1, proportion of energy in bacterial cells with respect to fermented hexose energy--E3 (P < 0.001) and the effectiveness of microbial proteosynthesis--YATP (P < 0.001), Tab. IV, as a result of defaunation. The total number of protozoa and the number of some species, especially the number of big entodinio-morphid protozoa, were markedly higher (p < 0.001) for the barley diet--Tab. V. The number of protozoa decreased rapidly within three days after the system initiation. Later on, the values were more or less steady. PMID- 1413391 TI - [Changes in the amino acid levels in hydrolysates of bacteria adhering to the rumen in sheep during feeding with high and low nitrogen diets]. AB - The effects of low and high nitrogen diets on amino acid levels were studied in hydrolyzates of ruminal bacteria adhered to four topographically different anatomic parts of the ruminal wall (dorsal, ventral and caudal parts as well as reticulum) in 18 sheep + of the Slovak Merino breed divided into three experimental groups. The epimural bacteria of the dorsal and ventral parts of the ovine rumen revealed the most sensitive reaction to the varying amounts of nitrogen ingested with the diet. In hydrolyzates of ruminal bacteria adhered to the dorsal and ventral epithelium, 15 and 14 amino acids were changing (Figs. 1, 2). In hydrolyzates of epimural bacteria, a sensitive reaction was observed in the following amino acids: alanine, histidine, thyroxin, arginine and proline (Tabs. I-IV). In all topographical and anatomical parts of the rumen, both alanine and histidine levels in hydrolyzates of epimural ruminal bacteria significantly increased with the diet with high-nitrogen content fed, but was falling in sheep fed with low-nitrogen diet. Changes in alanine concentrations may be explained by the fact that alanine forms a part of the mechanism for short time storage of ammonia in bacterial cells (Bartos, 1987). The fact that alanine is in its lack deaminated to pyruvate (Havassy, 1976) is explained by significant fall in alanine contained in hydrolyzates of bacterial proteins when fed low nitrogen diets. Significant fall in alanine in shortage of amino acid bound nitrogen can be explained by the fact that under these conditions, the alanine skeleton is being incorporated in to 80% of amino acids synthetized de novo by ruminal bacteria (Syvaoja and Kreula, 1980). When sheep flock was fed the high nitrogen diet, thyroxin and proline levels were significantly reduced in hydrolyzates of epimural bacteria from all parts of the rumen, while low-nitrogen diet significantly increased the concentrations of both given amino acids in comparison with the control. Bartos (1987) gives in his study the table containing weight representation of different amino acids in proteins of bacteria of the ruminal content compiled on the basis of data of several authors. These data principally correspond to the results of our measurements in hydrolyzates of epimural bacteria. The highest weight representation of amino acids in hydrolyzates of epimural bacteria was found for glutamic acid, aspartic acid and arginine, while the lowest ones were detected for thyroxin, proline and phenylalanine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1413392 TI - [Nuclear volume of cells in the stratum granulosum and theca folliculi interna of the largest dominant and atretic tertiary follicles in sheep during the selection process]. AB - According to available literary data, an increased nuclear volume of endocrine gland cells, various structures of the diencephalon and endocrine ovarial structures could be observed when the respective organs and structures were more active; a decreased nuclear volume was revealed when the activity of the respective organ or its structure was suppressed (Mess, 1962; Maracek and Arendarcik, 1976, 1978). Attention was paid to the karyometric analysis of follicular cells of the stratum granulosum (SG) and secretory cells of the theca folliculi interna (TFI) during selection of the dominant ovulatory follicle (DOF). The aim of this study was to determine differences in hte nuclear volumes of the granulosa follicular cells and the secretory cells of the inner theca of the DO1F in comparison with the largest atretic follicles (AF) as well as to verify the use of karyometric variance analysis for the evaluation of the selection process of the dominant ovulatory tertiary follicle. Histological sections were prepared from large DOF and AF from the ovaries of 18 sheep aged 3 5 years and held under standard conditions of a controlled herd. Control group I (n = 3) consisted of Wallachian sheep on day 15 of the sexual cycle (day 0). Excisions of ovaries from the animals of the experimental group (n = 3) were made on day 16 of the cycle after i.m. treatment with 120 micrograms GnRH 10 and 7 hours prior to sampling. Control group II (n = 3) consisted of Tsigai sheep at the 9th or 10th day of the oestrous cycle (hour 0) and three experimental groups (n = 3 each) consisted of Tsigai sheep 24, 48 and 72 hours after i.m. treatment with 125 micrograms cloprostenol. After excision the ovaries were fixed in neutral formaline, cut into 4 mm thick transverse segments and subjected to standard histological processing. After staining with Harris' HE the 5-7 microns thick sections were karyometrically evaluated at a magnification of 2200 x according to the method of Palkovits (1961) using the PC programme Karyotest 03 (Maracek et al., 1991). 200 cells were evaluated from each sample and both cell types; altogether 7200 cells were examined. GnRH treatment (Dirigestran inj. Spofa) increased the nuclear volume of follicular cells (SG) in the dominant ovulatory follicle in the process of selection (Tab. I, Fig. 1). The former, however, reduced the nuclear volume not only of the SG follicular cells of LAF (Tab. II, Fig. 2) but also of the secretory cells of both the DOF and AF theca interna (Tab. II, Figs. 3, 4). Cloprostenol treatment (Oestrophan inj. Spofa) affected the follicular cells of the granulosa in the dominant ovulatory follicle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1413393 TI - [Antiproteolytic activity of blood and cervical mucus in sheep after hormonal ovarian stimulation and gamma ray irradiation (2.45 Gy) during anestrus]. AB - The antiproteolytic activities of the blood plasma (BP) and cervical mucus (CM) determined as trypsin inhibiting activities (TIA) where trypsin served as a model serine protease, were variable after superovulatory stimulations of ewes and after their gamma irradiation (2.45 Gy). TIA's were determined from the reduction in the bovine trypsin hydrolysis of the low-molecular chromogenic substrate N alpha-tosyl-L-arginyl-p-nitro anilide (TAPA) (Bartik et al., 1974). The inhibition was expressed in per cent when delta A405 = 1.0 for 10-minute incubation at 25 degrees C, pH = 8.05, 0.2 mol/l tris-HCl buffer, was taken as 100%. Student's t-test was used for the statistical evaluation. A hundred ewes of the Merino breed were applied Agelin vaginal tampons (20 mg chlor-superlutin per head) on day 1 for 10 days in the anoestric period (May). A part of these ewes were subjected to whole-body gamma irradiation on days 6 to 11. When the irradiation was completed and the tampons were taken out, the ewes (three to four years old lambing ewes, yearling ewes) were stimulated to superovulations by an administration of 1500 IU serum gonadotropin (SG) or 450 IU follicle stimulating hormone (FSH). These parameters were followed in the subsequent 5-6 days: BP TIA (Figs. 1 and 4), fraction of low-molecular BP (n) TIA (Figs. 2 and 5), CM TIA (Figs. 3 and 6). Fig. 7 shows the average values of the results. The lambing ewes and yearling ewes had various responses to irradiation and superovulatory stimulation. Gamma irradiation eliminated the increase in BP TIA (P < 0.001) in the ewes after stimulations (Fig. 1a, b). The yearling ewes showed nonsignificant changes (ns) as their responses to SG stimulations and gamma irradiation, but the responses on the particular days of the trial were different (Fig. 1c, d--FSH stimulation). Similar changes were observed in the BP nTIA fraction. The changes in the average values of CM TIA were nonsignificant in the lambing ewes, the gamma irradiation reduced CM TIA only after FSH stimulation (P < 0.002). The amount of cervical mucus decreased after stimulations and irradiation, the thickness of ovarian epithelium and muscles was reduced in the particular parts, differently in lambing ewes and in yearling ewes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1413394 TI - [The effect of fatty acids in the feed on xanthine dehydrogenase activity in the Japanese quail]. AB - The aim of the present study is to determine the effect of different fatty acids on the amino acid catabolism judged on the level of xanthine dehydrogenase (XDH). The model system of protein depletion with subsequent repletion was used in the trial consisted of Japanese quails 71 days old. In the period of protein repletion, the fatty acid (stearic, palmitic, oleic, linolenic, linoleic and lauric, respectively) was used instead of common fatty compound in the diet. Specific activities of XDH in liver, kidneys and pancreas of quails were tested dynamically from the first to the eighth day of feeding. It was demonstrated that neither lauric, palmitic nor oleic acid, respectively, had an effect on the development of the specific activity of XDH (Fig. 3). Stearic acid as a sole fatty compound in the diet however evoked reactibility of XDH in liver or in pancreas in different way as in kidneys (Fig. 4). The dynamics of the XDH development in kidneys was practically identical than that in the control. However, XDH in liver and pancreas raised statistically already from the first day of feeding. The effects of linoleic and linolenic acids on the development of specific activity of XDH were organ selective, too (Fig. 5). XDH in kidneys was shown in the same manner as in the control group. In liver and pancreas, however, the specific activity of XDH was diminished markedly just from the first day of feeding. PMID- 1413396 TI - [A method for detection of cryptosporidial oocysts in mammals and birds]. PMID- 1413395 TI - [Continuous intravenous anesthesia in dogs using a combination of xylazine, ketamine and guaifenesin]. AB - The tested anaesthesia through a permanent infusion of a xylazine, ketamine and guaifenezine (XKG) mixture was used in ten experimental dogs without clinical signs of a disease and in fifty two patients during different surgical interventions. After joint i.m. atropine (0.05 mg/kg) and xylazine (2 mg/kg) premedication, anaesthesia in dogs was induced by an i.v. administration of 1% ketamine at a dose of 2 mg/kg, and the XKG was infused instantly after the previous treatment. The mixture contained 2.0 ml of 5% ketamine and 1.25 ml of 2% xylazine added to 100 ml of 5% guaifenezine. The infusion was applied at a rate of 3.3 ml/kg for the first five minutes and then it was maintained at constant values of 2.2 ml/kg during the whole surgical intervention (Tab. I). The induction and course of anaesthesia, and waking up and recovery from anaesthesia were evaluated in all dogs, and the trias values were also followed. These additional parameters were followed in the test group: breathing volumes, ECG values and acid-base balance parameters were determined from the collected blood samples. The observation of measurable parameters (Figs. 1 to 5) and ECG analysis did not demonstrate any large departures from the starting values, and the changes in the acid-base balance (Tab. II) suggest the partly compensated respiratory acidosis. On the basis of our results, we can recommend this tested method for general anaesthesia particularly of dogs of larger breeds and for longer-lasting operations. This method is suitable to be used first of all in the veterinary establishments where inhalation anaesthesia is not practicable. PMID- 1413397 TI - [Descent of ova and embryos in cows superovulated with serum gonadotropin]. AB - The descent and localization of eggs and embryos in individual segments of the reproductive tract of superovulated cows were studied in this work. For the induction of superovulation, serum gonadotropin (PMSG, Ivanovice in Hana) at a dose of 2,500-3,500 I.U. was used, in combination with 0.5 mg of Cloprostenol (Oestrophan, Spofa), administered 48 hours after gonadotropin treatment. The start of superovulation fell on days 9 to 12 of the sexual cycle and was conditioned by the presence of the corpus luteum (CL). After the onset of the heat, 2-3 inseminations were carried out using fresh semen. Donor cows were slaughtered 3, 4, 5, 6, and 7 days after the second insemination and isolated reproductive organs (Fig. 1) were divided into five segments (two on oviducts and three on uterine horns) by the applied ligature. In laboratory conditions superovulation response was determined accurately, the volume of ovaries was assessed according to water displacement and the segments of oviducts and uterus were rinsed with TCM 199 or PBS supplemented with FCS. 3, 4, 5, 6, and 7 days after insemination (Tab. I). 18.1 (+/- 3.55), 12.4 (+/- 0.91), 19.2 (+/- 2.86), 20 and 23 (+/- 2.44) CL on average were recorded, which corresponded to the ovulation of 64, 50, 56, 71 and 72 percent of stimulated follicles (Fig. 2). Within 3 to 7 days after insemination nearly triple enlargement of ovaries was also observed (Tab. I, Fig. 3). During the lavage of individual segments of the tubular reproductive tract, 38 per cent of eggs and embryos were detected in the uterus as early as 3 days after insemination (Tab. II). Unfertilized eggs and degenerated embryos were found in the 2nd and 3rd uterine segment, embryos at the stage of 8-16 blastomeres were localized in the 1st and 2nd segment of the uterus. Four days after insemination (Tab. III), about 64 per cent of eggs and embryos at the stage up to 16 blastomeres were found in the uterus, but embryos up to 32 blastomeres were still flushed out of the oviduct. On day 5 after insemination, 92 per cent of eggs and embryos were released into the uterus, being localized mostly in the cranial and medial part of the uterus (Tab. IV). 7.5 per cent of recovered eggs and embryos at the stage of early or compacted morulae were still detected in the oviducts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1413398 TI - [The effect of high-dose ultraviolet irradiation on sodium, calcium and aldosterone in the blood of calves]. AB - Five Holstein-Friesian calves, from one sire, with prevalent black hair coat pigmentation were used in the experiment. The mean age was 33 days and the mean live weight 51 kg. The animals were exposed free running without interruption for 12 hours to an artificial ultraviolet light in the range of 280-320 nm. The mean doses of radiation was 179.10(-10) J/h/m. One-spot high-pressure mercury discharge lamps Tesla RVK 400 W were used as a radiation source. The dose rate was estimated from measurements by a spectral photometer with filter UG 2 for absorbtion of visible light located at the height of the back of standing calf. Blood samples were collected immediately before the beginning of treatment and after 5, 12, 24, 48 and 72 hours. The blood plasma aldosterone was measured by radioimmunoassays, the levels of sodium, potassium and calcium in blood plasma by flame spectrophotometry. Double classification variance analysis and evaluation according to the Snedecor F-test, the contrast effect test according to Duncan and regression analysis were used for statistical evaluation. Compared to the first sampling, sodium increased significantly after 5 and 12 hours of exposure (Tab. I) to 138.1 and 138.3 mmol/l, respectively. In the subsequent samplings this trend continued up to 72 hours from the beginning of irradiation (140.5 mmol/l). The potassium level did not change statistically significantly. Owing to an excessive irradiation, the calcium concentration increased significantly. The greatest increase occurred after 12 hours of irradiation (from 2.29 mmol/l to 2.61 mmol/l) and after 36 hours from the end of irradiation (2.70 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413399 TI - [Production of progesterone and testosterone in ovarian granulosa cells in sows after administration of nonapeptide hormones in vitro]. AB - In the present paper the effects of nonapeptide hormones and of some of their chemical analogues were investigated on progesterone and testosterone production in granulosa cells of sow ovaries; the experiments were made in vitro. This objective was given by data on potential regulatory roles of nonapeptides at the level of hypothalamus, pituitary and reproductive organs. The goal of this experiment was to analyze the effects of various doses of oxytocin (OT), arginine 8-vasopressin (AVP), arginine-8-vasotocin and of some of their analogues on progesterone and testosterone production in vitro in granulosa cells of sow ovaries. The production activity of granulosa cells was investigated which were obtained from slaughtered sows without any changes in their reproductive process and abnormalities in their reproductive organs. Follicles of the size 2-5 mm without marked paleness in the early follicular phase were selected for aspiration. Granulosa cells with determined viability (more than 75%) and concentration (2 million/ml) were cultivated in defined culture conditions (37.5 degrees C, 5% CO2) after threefold resuspension and centrifugation of follicle fluid. These hormonal preparations were used in the experiments: pFSH, synthetic OT, synthetic AVP, synthetic AVP with antidiuretic effects and synthetic AVT. Progesterone and testosterone concentrations were analyzed radioimmunoanalytically using commercial kits of the Institute of Radio ecology and Nuclear Technology at Kosice. Statistically significant differences between the groups were evaluated by Student's t-test. The administered preparations were found to influence progesterone and testosterone production in dependence on the doses applied (Figs. 1-6). OT stimulation of progesterone production in granulosa cells indicated its regulatory role in relation to secretion of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413400 TI - [Experimental chronic phenylmercuric chloride poisoning in pigs]. AB - Four gilts, sisters from one litter, aged 70 days and weighing 20-24 kg, were used for a trial. Two experimental gilts (P) were administered an experimental feed mixture containing phenylmercury chloride (40 mg/kg). Two control gilts (K) were fed the same mixture but without phenylmercury chloride. P gilts began to lag behind in their growth from day 60 of the experiment, they manifested nonphysiological postures (dog's sitting posture), paresis of hind limbs and uncoordinated movements. P gilts had cloudy, orange-brown urine from day 70 and from day 75 they began to suffer from diarrhoea. Mercury (Hg) contents in urine and blood serum of P gilts were irregularly variable: urine 0.58-2.15 mg/l, blood serum 0.02-0.37 mg/l. Hg content in excrements of P gilts fluctuated from 23 to 26 mg/kg. Vitamin A concentrations in blood serum and liver decreased in P gilts. Phenylmercury chloride feeding caused mutagenic changes in peripheral lymphocytes of P gilts (an increase in the number of aberrant cells from 2-3% to 8-9%) and reduced IgA, IgM and IgG immunoglobulin levels in blood serum. Pathological lesions were observed in the colon, kidneys and liver. None of the above mentioned changes were observed in K gilts. Increased resistance to the negative effects of Hg was found in one experimental gilt. In comparison with K gilts, Hg concentrations in P gilts after 130 days of the experiment increased as follows: 427 times in kidneys, 333 times in liver, 106 times in guts, 71 times in pancreas, 53 times in ovaries, 50 times in muscles, 47 times in bristles and 16 times in the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413401 TI - [The effect of repeated administration of carbetocin (Depotocin, Spofa) in the first days postpartum on levels of thyroxine, triiodothyronine, 17 beta estradiol, progesterone and on fertilization]. AB - Application of new procedures in the sphere of the control of sexual functions requires an extension of present knowledge of postparturient endocrinium or endogenic factors comprised in postparturient physiology of sexual activity. According to recent data, oxytocin, besides its uterotonic and luteolytic activity, acts as an ovarian factor in the local intrafollicular regulation of stereidogenesis and as a modulator of uterine secretion of prostaglandines. Based on present knowledge of oxytocin effects, this study was aimed at investigation of the influence of repeated carbetocin (Depotocin inj. Spofa) administration on the dynamics of changes in thyroxine (T4), triiodothyronine (T3), 17 beta estradiol (E2), progesterone (P4) concentrations and their mutual correlations from the 36th hour till the 51st day after parturition. Simultaneous study of a possible delayed influence of applied carbetocin on conception of ewes after oestrus evocation on day 51 after lambing was carried out. Nineteen ewes of the Slovak Merino breed, lambed in the first decade of February, were assigned to the experimental (n = 9) and to the control group (n = 10). Experimental ewes were subjected to repeated postparturient carbetocin treatment at the dose 0.07 mg per animal. The first dose was applied i. m. in 24 hours, and the second in 72 hours after parturition. On day 51 oestrus was induced in nine ewes of each group by combined treatment with chlorsuperlutin (Agelin, vaginal pessaries, Spofa) and PMSG (500 I.U./animal). On the day of PMSG application ewes were housed together with rams for the period of the next six days. Samples of blood were taken 24 hours before parturition (-1st day), up to 36 h after parturition and on days 4, 7, 14, 17, 21, 25, 34, 42 and 51 after parturition. Concentrations of T4, T3, E2 and P4 were determined by commercial kits RIA-test-T4; RIA-test-T3; RIA-test ESTRA and RIA-test-PROG (URVJT Kosice). Animal of the control group showed variations of T4 concentrations (Tab. I, Fig. 1) at the level of original values (59.4 +/- 9.69 nmol.l-1) up to the 21st day with the exception of temporary drop on day 4 and rise on day 7, insignificant compared to the -1st day. T4 concentrations of the control group displayed an intermittent increasing trend with the statistically insignificant peak after 36 h and on day 17, compared to the -1st day. After the 21st day controls revealed a sustained moderate increase while the experimental ewes displayed a decline of its concentrations until the 51st day.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1413402 TI - [Levels of mercury in samples of bees and honey from areas with and without industrial contamination]. AB - Increasing numbers of specialists have been concerned with the problem of friendly environment in relation to man as well as to farm and wild animals. Greater interest in the biological monitoring of environment and ecosystem contamination can be observed. Determination of residues of organic and inorganic substances in bees (Apis mellifera) and in their products is one of effective possibilities of environmental pollution monitoring. Our work was aimed at the study of mercury levels in bees and their products. Mercury levels were determined in the head, abdomen and thorax of bees (Apis mellifera) from 20 bee populations coming from industrially contaminated areas with a dominant load of mercury (10 populations) and from uncontaminated areas. Mercury levels were determined simultaneously in honey coming from both contaminated and uncontaminated areas. The following mercury levels were found in bees from the contaminated area: heads 0.029-0.385 mg/kg, thorax 0.028-0.595 mg/kg and abdomen 0.083-2.255 mg/kg. Mercury levels in samples from uncontaminated areas ranged from 0.004 to 0.024 mg/kg in the heads, from 0.004 to 0.008 mg/kg in the thorax and from 0.008 to 0.020 mg/kg in the abdomen. In honey samples from the contaminated and uncontaminated areas mercury levels ranged from 0.050 to 0.212 mg/kg and from 0.001 to 0.003 mg/kg, respectively. The results of sample analyses for mercury loads in bees and honey from both contaminated and uncontaminated areas are given in Tab. I. Mean mercury levels in the single parts of the body in Apis mellifera and in honey from contaminated and uncontaminated areas are given in Figs. 1, 2, 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413403 TI - A survey of epithelial odontogenic tumors and cysts in dogs and cats. AB - A retrospective histologic study of 12 canine and eight feline epithelial odontogenic tumors and cysts was conducted from oral masses (n = 3,917) obtained between 1980 and 1990. No sex or breed predilection was identified. Ameloblastoma was observed in two dogs (case Nos. 1, 2) 6 and 8 months of age. Calcifying epithelial odontogenic tumors were seen in a dog (case No. 3) and in two cats (case Nos. 4, 5) between 8 and 16 years of age. Ameloblastic fibroma (or fibroameloblastoma) was observed in cats (case Nos. 6-10) only. Inductive fibroameloblastoma was observed in four cats (case Nos. 6-9) up to 1 year of age, whereas ameloblastic fibroma was seen in a 14-year-old cat (case No. 10). A single ameloblastic odontoma was identified in a 20-month-old dog (case No. 11). Two complex odontomas occurred in a 6-month-old (case No. 12) and a 4-year-old (case No. 13) dog. Odontogenic cysts were identified in five dogs (case Nos. 14 18) aged 4.5 months to 16 years and in a 1-year-old cat (case No. 19) and have not been previously reported in these species. These cysts were lined by a stratified epithelium reminiscent of the appearance of ameloblastic epithelium. An odontogenic keratocyst with prominent central parakeratotic keratinization was identified in one 9-year-old female dog (case No. 20). Almost all epithelial odontogenic tumors were circumscribed, benign tumors that warranted a good prognosis for survival, although local recurrence may have followed (or may follow) incomplete excision. Calcifying epithelial odontogenic tumors may be locally invasive. Of six odontogenic cysts (case Nos. 14-19), two (case Nos. 15, 18) gave rise to basi-squamous carcinomas. The classification and behavior of epithelial odontogenic tumors and cysts in human beings, dogs, and cats are discussed. PMID- 1413404 TI - Correlation between histologic diagnosis mean nucleolar organizer region count and prognosis in canine mammary tumors. AB - In this study, surgically excised mammary tumors from 98 bitches were graded histologically, and the grade was compared with the mean nucleolar organizer region (NOR) count in silver-stained paraffin-embedded sections. Histologically benign tumors, papillary adenocarcinomas, and intraductal carcinomas showed relatively little variation; the mean count for each category was between three and four NOR per nucleus. There was, however, a significant increase in the NOR counts in tubular and solid carcinomas. This increase was most pronounced for tumors that showed evidence of infiltration into the surrounding connective tissues. The mean NOR count for noninfiltrative carcinomas was 5.1, and that for invasive carcinomas was 7.3 (P less than 0.03). The mean NOR count for individual carcinomas ranged from 2.0 to 12.3, and a significant correlation was found between an increased NOR count and tumor-related death during the first post surgical year. The 39 bitches in which the tumor had an NOR count less than 8.0 had a generally favorable prognosis; only six (15%) died as a result of the original neoplasm. In contrast, 18/21 dogs (85%) with a carcinoma having an NOR count greater than 8.0 died from the tumor during the first post-surgical year. A similar, although less pronounced result was obtained specifically for invasive carcinomas, in which 3/12 (25%) tumors with an NOR count less than 6.0 resulted in the death of the host, compared with 17/20 (85%) that had an NOR count greater than 6. By using this technique, it is possible to identify a subgroup of bitches with invasive mammary carcinomas that have a very poor prognosis following apparently adequate surgical ablation of the primary tumor. PMID- 1413405 TI - Correlation of DNA ploidy to tumor histologic grade, clinical variables, and survival in dogs with mast cell tumors. AB - By using flow cytometry, a retrospective analysis of the DNA content of 40 primary canine mast cell tumors and seven lymph nodes that contained metastatic mast cell tumor from 44 dogs of various breed, sex, and age was performed on formalin-fixed, paraffin-embedded samples of the tumors and nodes. These samples were chosen according to the following criteria: samples contained sufficient well-preserved tumor tissue in the paraffin block for processing, sufficient patient history data were available, clean and homogeneous cell suspensions were obtained after processing, and interpretable DNA histograms were produced on analysis. The ploidy data obtained were compared with the histopathologic grade, the anatomical site of occurrence, the clinical stage of the tumors, and the survival of the dogs. Over 70% (29/40) of the mast cell tumors were diploid. Three metastatic mast cell tumors in lymph nodes had the same ploidy status as their corresponding primary tumors. In five dogs, mast cell tumors from multiple sites in each dog displayed similar ploidy status. Of 26 dogs evaluated for survival times, 69% (18/26) had diploid tumors and 31% (8/26) had aneuploid tumors. When numbers of diploid versus aneuploid tumors were compared, no significant difference was found between any two grades, clinical stages, or anatomic sites. A significant difference (P = 0.02) was found, however, between aneuploid and diploid tumors when comparing Stage I and non-Stage I disease. The Kaplan-Meier survival plot indicated a tendency towards an increased survival within the first year in dogs with diploid versus aneuploid tumors (P = 0.06). PMID- 1413406 TI - Characterization of morphologic changes and lymphocyte subset distribution in lymph nodes from cats with naturally acquired feline immunodeficiency virus infection. AB - Lymph nodes were collected at biopsy or necropsy from 18 cats with naturally acquired symptomatic feline immunodeficiency virus (FIV) infection and from 18 seronegative cats. Thirty-five of the cats were domestic shorthairs and one was a Persian cross. The cats ranged from 7 months to 16 years of age and were mainly obtained from California veterinary practitioners, a California cattery, and a Veterinary Teaching Hospital. Based on clinical signs present at tissue collection, ten FIV-infected cats fell into the acquired immunodeficiency syndrome (AIDS)-related complex (ARC) clinical stage and eight in the terminal (AIDS) stage of FIV disease. All cats were FeLV negative by antigen ELISA. Histologic sections of lymph nodes from each cat were examined blindly and were categorized as hyperplastic, involuting, mixed hyperplastic and involuting, depleted, or normal based upon subjective evaluation of follicles and paracortex. The relative abundance of plasma cells was evaluated in methyl green pyronin (MGP) and hematoxylin and eosin-stained sections. Similar numbers of FIV seropositive and -seronegative cats fell into each lymph node category. The only difference evident between FIV-infected cats and control cats was in the degree of plasmacytosis present; moderate to marked plasmacytosis was present in 13/18 FIV-infected cats but in only 3/18 control cats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413408 TI - A morphologic and immunocytochemical study of hepatic neoplasms in cats. AB - A retrospective study was done of 47 neoplasms of the hepatic and biliary systems from 47 cats brought to The Animal Medical Center over a period of 10 years (1980 to 1989). Histologic examination of specimens taken at necropsy revealed that 87% (41/47) of the hepatic neoplasms were epithelial and 13% (6/47) were nonepithelial. Of the epithelial tumors, 25/47 (53%) were of intrahepatic bile duct origin, 9/47 (19%) were of hepatocellular origin, 5/47 (11%) involved the extrahepatic bile ducts, and 2/47 (4%) were adenocarcinomas of the gall bladder. Of the nonepithelial neoplasms, hemangiosarcomas were more common, 5/47 (11%), than leiomyosarcomas, 1/47 (2%). Multiple liver lobes were involved in 21/34 (62%) of the epithelial and all six of the nonepithelial intrahepatic neoplasms. Most of the bile duct adenocarcinomas (6/9) were predominantly characterized by acinar structures with mucin production, diffuse necrosis, and little desmoplasia. The hepatocellular carcinomas were characterized by three patterns trabecular (five tumors), pseudoglandular pattern (two tumors), and anaplastic (one tumor). The hepatic carcinoid was characterized by various-sized groups of acinar and rosettelike structures, some with lumens, separated by thin fibrovascular stroma. The extrahepatic bile duct adenocarcinomas (4/4) were acinopapillary with moderate desmosplasia, whereas the adenocarcinomas of the gall bladder had elongated tubular structures lined by anaplastic cells and a severe desmoplastic reaction. The neuroendocrine carcinoma of the extrahepatic bile duct, the hemangiosarcomas, and the leiomyosarcoma had morphologic features characteristic of these neoplasms. Two of the 16 (13%) bile duct adenomas had anaplastic and precancerous changes. Residual benign components were seen in 10/15 (67%) of the biliary adenocarcinomas, 4/9 (44%) of the intrahepatic bile duct adenocarcinomas, and all of the extrahepatic bile duct adenocarcinomas and gall bladder adenocarcinomas. Results of immunohistochemical studies of the biliary neoplasms were similar to those described in studies of biliary neoplasms in human beings. Results of this study revealed that the frequency of different types of hepatic neoplasms in cats varied from that seen in dogs and human beings, but the morphologic features were comparable. PMID- 1413407 TI - Hematologic features of iron deficiency anemia in llamas. AB - Iron deficiency anemia was identified and characterized in three 14 to 29-month old male llamas (llama Nos. 1-3) from separate herds in Colorado. The identification of iron deficiency anemia was based on hypoferremia (serum iron = 20-60 micrograms/dl), erythrocytic features, and hematologic response to iron therapy. The anemia was moderate and nonregenerative and characterized by erythrocyte hypochromia, microcytosis (mean cell volume = 15-18 fl), and decreased mean corpuscular hemoglobin concentration (36.0-41.0 g/dl). Morphologic features unique to llamas with iron deficiency anemia included irregular distribution of hypochromia within erythrocytes and increased folded cells and dacryocytes. The cause of iron deficiency was not determined. The llamas were treated with various doses and schedules of parenteral iron dextran. Two of the llamas were monitored for up to 14 months after the start of iron therapy and experienced increases in hematocrit and mean cell volume values. In one llama, progressive replacement of microcytic cells with normal cells was visualized on sequential erythrocyte volume distribution histograms following iron therapy. PMID- 1413409 TI - Massive thymoma with medullary differentiation in a dog. PMID- 1413410 TI - New meat hygiene regulations published. PMID- 1413411 TI - Historical, clinical and laboratory features of 126 hyperthyroid cats. AB - The historical and clinical features and the haematological and biochemical changes in 126 cats with hyperthyroidism are described; 125 of the cats were domestic short- or longhaired, and one was a chinchilla. There were 62 males and 64 females with a mean age of 13.0 years. The duration of signs ranged from two days to two years with a mean of 5.4 months. The historical and clinical features were weight loss, polyphagia, polyuria/polydipsia, tachycardia, hyperactivity, diarrhoea, respiratory abnormalities, other cardiac abnormalities, skin lesions, vomiting, moderately raised temperature, decreased activity, decreased appetite, congestive cardiac failure, haematuria and intermittently decreased appetite. Goitre was palpable in 123 cats. The serum total thyroxine concentrations of the cats were more than three standard deviations above the mean of the reference range. Serum total tri-iodothyronine concentrations ranged from 0.78 to 14.96 nmol/litre and were within the reference range in 11 of the cats. Mild hyperthyroidism was a much commoner cause of high normal or marginally above normal thyroid hormone concentrations than severe, concurrent, non-thyroidal illness. Other common biochemical changes were increased of serum alanine aminotransferase, urea, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase. There were minimal changes in the red cell parameters. Leucocyte changes showed two trends: a mature neutrophilia, either with or without an accompanying leucocytosis often in association with a lymphopenia, or an eosinophilia, either with or without a lymphocytosis. PMID- 1413412 TI - Non-patent left uterine horn and segmental aplasia of the right uterine horn in an infertile cat. PMID- 1413413 TI - Giardia in straw-necked ibis (Threskiornis spinicollis) in Western Australia. PMID- 1413414 TI - Foxoil--a toxic experience in lambs. PMID- 1413415 TI - Equine vaccination. PMID- 1413416 TI - Veterinary nursing examinations. PMID- 1413417 TI - Possible complication with rumen boluses. PMID- 1413418 TI - Copper toxicosis in Bedlington terriers. PMID- 1413419 TI - Is Escherichia coli a phocine pathogen? PMID- 1413420 TI - Possible complication with rumen boluses. PMID- 1413421 TI - An outbreak of blue-eared pig disease (porcine reproductive and respiratory syndrome) in four pig herds in Great Britain. AB - The clinical syndrome of a new disease of pigs in four herds in the Humberside area is described. The first signs of the disease were anorexia, lethargy and pyrexia with up to 60 per cent of the dry sows affected. These signs were followed by an increased incidence of abortions which occurred in up to 3.3 per cent of sows, premature farrowings in up to 20.6 per cent of sows and stillbirths and late mummification which affected up to 26.0 and 18.8 per cent of fetuses, respectively. Mortality in neonatal and pre-weaning pigs reached up to 88 per cent and respiratory disease of high morbidity and low mortality occurred in fattening pigs. There were infertility problems in sows, with an increase in returns to service and a failure to show oestrus after weaning or aborting. The signs of the disease in boars were anorexia and malaise. Cyanosis of the extremities affected up to 2 per cent of the animals. The outbreak lasted 11 weeks in all the herds. PMID- 1413423 TI - Purulent streptococcal lymphadenitis in swine. PMID- 1413422 TI - Acute tubulo-interstitial nephritis in a dog after halothane anaesthesia and administration of flunixin meglumine and trimethoprim-sulphadiazine. AB - Acute tubulo-interstitial nephritis was diagnosed post mortem when a dog died four days after surgery for a femoral head resection. Possible causative factors associated with halothane anaesthesia, flunixin meglumine analgesia and prophylactic antibiotic therapy with trimethoprim-sulphadiazine are discussed. It is concluded that death was due to renal failure associated with tubulo interstitial nephritis as a result of a combination of ischaemic and toxic events. PMID- 1413425 TI - Out-of-hours cover. PMID- 1413424 TI - Actinomyces pyogenes mastitis among lactating cows following foot-and-mouth disease. PMID- 1413426 TI - Veterinary nurse training. PMID- 1413427 TI - Out-of-hours cover. PMID- 1413428 TI - Systemic pasteurellosis. PMID- 1413429 TI - Use of free-access minerals. PMID- 1413430 TI - Preliminary observations on inhalation and intradermal challenges of horses with oil seed rape. AB - Horses with asymptomatic or symptomatic chronic obstructive pulmonary disease (COPD) and control horses were challenged with oil seed rape either by exposure to a field of flowering Brassica campestris for six days, or by an inhalation challenge with freshly collected pollen from Brassica napus, or by inhalation challenge with a commercial extract of B napus pollen. Clinical and bronchoscopic examinations showed that the challenges did not induce detectable pulmonary disease in the control or asymptomatic COPD affected horses and did not significantly affect their pulmonary mechanics, arterial blood gas tensions, arterial pH or the cytology of bronchoalveolar lavage fluid. However, the challenges with fresh B napus pollen and the commercial extract of B napus pollen exacerbated the pulmonary disease in some of the symptomatic horses, possibly owing to non-specific toxicity or non-specific bronchial hyperresponsiveness. Intradermal testing with the commercial extract of B napus pollen suggested that none of the horses were hypersensitive to this agent. PMID- 1413431 TI - Urethral conformation and position in relation to urinary incontinence in the bitch. AB - The conformation of the urethra, the position of the bladder neck and the distance between the external urethral orifice and the cranial pubic brim were compared in 30 continent and 30 incontinent bitches with incompetence of the urethral sphincter mechanism, using the measurements made from vagino urethrograms. The bladder neck was significantly (P less than 0.001) further caudal in incontinent dogs than in continent dogs. Its position was not affected by neutering and could not be explained by the degree of urethral curvature. The distance from the external urethral orifice to the cranial pubic brim was correlated (P less than 0.001) with bodyweight but was not significantly different in the continent and incontinent bitches. In neutered animals, the distance between the cranial pubic brim and the external urethral orifice was significantly (P less than 0.05) shorter than in entire animals. PMID- 1413432 TI - Squamous cell carcinoma of the equine stomach: a report of five cases. AB - Five horses with squamous cell carcinoma of the stomach are described. The clinical findings included anorexia, weight loss, abdominal distension, abnormal chewing and swallowing behaviour and abdominal masses palpable per rectum in four cases. Haematological studies revealed a normocytic anaemia in three horses, and neutrophilia and hypoalbuminaemia in two. Analysis of peritoneal fluid revealed abnormal effusions in all five horses and neoplastic cells were identified in three of them. The tumours originated in the cardia and metastases were present in all the horses. Three of them had many small nodules covering the entire peritoneum. PMID- 1413433 TI - Effect of probenecid on disposition kinetics of ampicillin in horses. AB - The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present 25 hours after it was administered. The disposition kinetics of ampicillin were altered by the presence of probenecid and as a result the antibiotic had a slower body clearance (ClB; 109.4 +/- 6.71 ml/kg hours compared with 208.9 +/- 26.2 ml/kg hours) a longer elimination half-life (t1/2 beta 1.198 hours compared with 0.701 hours) and consequently a larger area under the plasma concentration versus time curve (AUC 92.3 +/- 5.09 mg/ml hours compared with 35.95 +/- 3.45 mg/ml hours) when compared with animals to which ampicillin was administered alone. The ampicillin concentrations observed suggest that the dosing interval for horses may be increased from between six and eight hours to 12 hours when probenecid is administered in conjunction with the ampicillin. PMID- 1413434 TI - Hepatic haemangioma in a pig. PMID- 1413435 TI - Bovine embryo transfer. PMID- 1413436 TI - Transplacental infection of a foal with Toxoplasma gondii. PMID- 1413437 TI - 'Mal seco' and grass sickness. PMID- 1413438 TI - Spread of F gigantica in Tanzania. PMID- 1413440 TI - Contagious bovine pleuropneumonia. A review. AB - The prevalence, characteristics of the aetiological agent, clinical signs, pathological changes, pathogenesis, epizootiology, microbiological and serological diagnosis, prevention, and control of contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subspecies mycoides SC.type, are reviewed. New aspects of the disease are discussed. A renewed interest in this disease is important because of outbreaks in Southern Europe since 1980. When, at the end of 1992, the national borders of the countries of the European Community are abolished, it is conceivable that the disease will be introduced by cattle imported into CBPP-free countries. PMID- 1413439 TI - Increased prevalence of Mycoplasma bovis in the Netherlands. AB - The epidemiology, therapy, and prevention of M. bovis infections are briefly reviewed. In a survey begun in 1982, M. bovis was found frequently in the respiratory tract [corrected] of veal calves and beef cattle with respiratory problems. In replacement calves infected with respiratory disease in dairy herds, however, the organism has only been detected since 1986. Respiratory tract specimens collected from calves with respiratory disease were submitted for examination for M. bovis from 1986 to 1991 and originated from 83 herds. Mycoplasma bovis was detected in specimens from 59 of the herds, 20% of which were dairy herds and 80% fattening herds. Arthritis caused by M. bovis was observed in 12 herds until July 1991. Since 1976 when the first mastitis outbreak caused by M. bovis was diagnosed, M. bovis has caused 14 more outbreaks. The number of diseased cattle varied from 1 tot 16 per farm, and clinical signs of mastitis varied from mild to severe. In all instances the infection has been eradicated from the herds. Because M. bovis can cause great losses in intensively reared cattle herds, it is advisable to separate purchased veal calves and beef cattle from dairy cattle to prevent further spread of M. bovis. PMID- 1413441 TI - Risks connected with the use of conventional and genetically engineered vaccines. AB - A review is given of real and potential risks connected with the use of conventional and genetically engineered live and dead vaccines. Special attention is given to live carrier vaccines expressing one or more heterologous genes of other microorganisms. Because most carrier vaccines are still in an experimental phase, there is only limited experience with the risks of carrier vaccines. There are three potential risks of live carrier vaccines which will be discussed: 1. Changes in cell, tissue, of host tropism, and virulence of the carrier through the incorporation of foreign genes. 2. Exchange of genetic information with other vaccine or wild-type strains of the carrier organism. 3. Spread in the environment. Only limited experimental data are available on changes in biological behaviour of microorganisms through the incorporation of foreign genes. For example, there are indications that vaccinia virus carrying the attachment protein G of respiratory syncytial virus (RSV) replicates better in lungs of mice than vaccinia virus carrying other genes of RSV. Poxviruses carry genes that probably determine their replication in different hosts. Exchange of such host tropism genes might alter their host spectrum. Recombination between herpesvirus vaccine or wild-type strains may lead to the appearance of virulent strains with of without heterologous genes. Before carrier vaccines are applied, these risks must be thoroughly evaluated case-by-case. Potential methods for the design of safe carrier vaccines are discussed. PMID- 1413442 TI - Clinical trial of long-acting oxytetracycline and piroxicam in the treatment of canine ehrlichiosis. AB - Forty-three dogs with canine ehrlichiosis were treated with long-acting oxytetracycline (TLA) at a dose of 20 mg/kg. In order to eliminate pain at the site of injection of TLA, varying doses of piroxicam were administered intramuscularly to the treated dogs. A minimum of 15 mg of piroxicam proved effective in eliminating pain and swelling at the TLA-injection sites, while fever was eliminated with a minimum of 10 mg of piroxicam 24 hours post treatment. Rapid restoration or improvement of appetite in treated dogs was also observed after treatment with piroxicam and TLA. Both TLA and piroxicam were found to be suitable for use in dogs. PMID- 1413443 TI - Hyperadrenocorticism in four cats. AB - This paper describes four cats with hyperadrenocorticism. Cat 1 showed polydipsia and polyphagia. Diabetes mellitus was initially diagnosed. As the animal appeared to be insulin resistant, pituitary and adrenocortical function tests were performed and the diagnosis of hyperadrenocorticism was made. Resistance to the high-dose dexamethasone suppression test was noticed in this cat. Pathological examination revealed a pituitary chromophobe adenoma. Cat 2 presented with diabetes mellitus, which was treated with insulin. The animal had a pendulous abdomen and its coat was in a poor condition. The low-dose dexamethasone suppression test demonstrated hyperadrenocorticism. Necropsy findings of pituitary tumour and hyperplasia of the adrenal cortex confirmed the diagnosis. Cat 3 showed clinical abnormalities indicative of hyperadrenocorticism, for instance, muscle weakness, alopecia, multiple abscesses. The diagnosis of hyperadrenocorticism was confirmed by the results of the lowe-dose dexamethasone suppression test. Pathological examination revealed an adrenocortical carcinoma. Cat 4 presented with polydipsia. The cause of this symptom was not found initially. One and a half years later additional symptoms, such as nephritis and polyphagia developed. Hyperadrenocorticism was diagnosed because of a palpable mass cranial to the left kidney. The diagnosis was confirmed by the results of the lowe-dose dexamethasone suppression test and the necropsy findings. PMID- 1413444 TI - Transdermal delivery and intramuscular injection of trimethoprim/sulphadiazine in sucking piglets. AB - The pharmacokinetics of a combination of trimethoprim (TMP) and sulphadiazine (SDZ) after topical application to sucking piglets was compared with the pharmacokinetics after intramuscular injection. A long-lasting and fairly constant SDZ/TMP concentration ratio in plasma was obtained after topical application. The mean plasma concentration of TMP ranged from 0.091 to 0.17 micrograms/ml and that of SDZ from 0.72 to 1.1 micrograms/ml for at least 24 h. TMP and SDZ had different half-lives after intramuscular injection. Transdermal delivery of a combined preparation of TMP/SDZ may be usable for colibacillosis of sucking piglets, although the bioavailability of the drugs is poor. PMID- 1413445 TI - The response of pigs experimentally infected with Trypanosoma brucei to isometamidium chloride therapy and the relation to nutrition. AB - Growing pigs were placed on feeds with high (Group A), medium (B) and low (C) dietary energy and were infected with a virulent stock of T. brucei. Eight weeks later, the infected pigs were treated with isometamidium chloride at 1 mg/kg live weight and all pigs were subsequently placed on a high energy diet to investigate their response to therapy. Clearance of T. brucei from blood was completed 72h after treatment. There was no evidence of relapsed infection up to eight weeks after treatment. Red blood cell parameters returned to normal four to six weeks after treatment with responses being fastest in Group A, B and C had gained about two-thirds of the live weight gains of their non-infected pair-fed controls. It appears that the retarded weight gain as a result of the infection persisted after therapy since drug-treated pigs did not gain as much weight as their non infected controls. PMID- 1413446 TI - Myocardial damage in cats that died after anaesthesia. AB - The necropsy findings of 85 cats that died up to six weeks after administration of injectable anaesthetics are described. The most obvious findings in these cats were degeneration and necrosis of heart muscle fibres followed and related to time after the administration of the anaesthetics, by infiltration of predominantly mononuclear cells and by an increase in collagenous connective tissue. The lesions were most obvious on the inner side of the myocardium, indicating that hypoxic injury occurred during anaesthesia. The possible mechanism of the damage to the heart and its role in the pathogenesis of cardiomyopathy in the cat is discussed. PMID- 1413447 TI - The effect of T. vivax infection in west African dwarf goats on energy and nitrogen metabolism. AB - To investigate how T. vivax affects metabolism in dwarf goats, nine wethers (infection group) given alfalfa pellets ad libitum were infected intravenously and food intake was recorded up to 49 days after infection in the infection group and in the control group (n = 9). Controls received the same diet, ad libitum before infection and in restricted amounts after infection in order to obtain similar intakes in the two groups. Digestible organic matter intake (DOMI) and nitrogen balance (NB) were determined during four balance trials. All animals were bled regularly to measure parasitaemia, packed cell volume (PCV) and a number of serum metabolites. All infected animals showed symptoms typical for T. vivax infection as judged by parasitaemia, PCV and rectal temperature. Infection had a non-uniform negative effect on food intake. Compared with controls at equal DOMI, NB was lower in infected animals, the difference being significant 4 weeks after infection. This was caused by a gradual increase in NB at equal DOMI of the control group. The NB of the ad libitum fed infected animals 2 and 4 weeks after infection was comparable to values normally found in healthy ad libitum fed dwarf goats with an equal DOMI. NEFA values in serum were significantly elevated after infection. Except for two infected animals with an extremely low food intake towards the end of the experiment, no rise in serum ketone bodies was evident. After infection, serum protein increased, differences with controls being significant 4 and 7 weeks after infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413448 TI - The interaction of Trypanosoma congolense and Haemonchus contortus infections in trypanotolerant N'Dama cattle. AB - The interactions between Trypanosoma congolense and Haemonchus contortus infections were studied in N'Dama calves. A total of 38 N'Dama bulls was divided into four groups and each group infected either with H. contortus 1 week after infection with T. congolense or with T. congolense 4 weeks after infection with H. contortus, or with either infection singly. Parasitological (faecal egg counts, parasitaemia), haematological (packed cell volume, white blood cell counts, albumin) and clinical parameters (body weight change, mortality rate) were compared among the various groups. The results showed a reduced prepatent period and a markedly increased pathogenicity of H. contortus infections in animals with a concurrent T. congolense infection. The most harmful combination was a H. contortus infection 1 week after the T. congolense infection which resulted in a progressive and severe anaemia, accompanied by hypoalbuminaemia, increased weight loss and high mortality. The anaemia induced by dual infections showed a low responsiveness to chemotherapy and in several cases supportive treatment did not help recovery. The results also showed that animals with a concurrent T. congolense and H. contortus infection ran a higher risk of succumbing during the infection, and also during 10 weeks following treatment. Although infections with T. congolense alone produced no clinical signs, they were found to significantly reduce the ability of infected animals to mount a normal response to a subsequent H. contortus infection. It was concluded that the increased H. contortus egg excretion observed in animals infected with both parasites might significantly increase the risk of nematode infections and that the reduced prepatent period might necessitate more frequent anthelmintic treatments. These interactions should, therefore, be considered wherever attempts are made to control these two diseases. PMID- 1413449 TI - Prevalence of Toxoplasma gondii antibodies in pastoral camels (Camelus dromedarius) in the Butana plains, mid-Eastern Sudan. AB - A total of 482 serum samples from pastoral camels in the Butana plains, mid Eastern Sudan, were tested for Toxoplasma antibodies by the latex agglutination test (LAT). Sixty-seven percent of the camels were seroreactive. The prevalence rate of seroreactivity increased significantly with age (P less than 0.01) and was highest among camels aged over 7 years (74.2%). The prevalence rate of seropositivity decreased proportionally with the level of serum dilution. At dilutions of 1:32 and above, the prevalence rate was 25.9%. There were no sex linked differences in seroreactivity. This study suggests widespread infection with Toxoplasma gondii among pastoral camels, a finding that warrants a closer look into the possible ways infection is acquired by camels in their arid environment, its economic impact, as well as its public health significance, especially among the nomads who consume cameline milk and liver raw. PMID- 1413450 TI - The effect of neutrophils, tumor necrosis factor, and granulocyte macrophage/colony stimulating factor on Babesia bovis and Babesia bigemina in culture. AB - Bovine neutrophils, human recombinant tumor necrosis factor-alpha (TNF), and bovine recombinant granulocyte macrophage/colony stimulating factor (GM/CSF) were added to microaerophilic cultures of Babesia bovis and Babesia bigemina to determine if those substances could inhibit growth. Incorporation of [3H]hypoxanthine by the Babesia spp. was utilized as an indirect measure of parasite growth. When neutrophils were added to cultures of B. bovis and B. bigemina, the highest percentage inhibition of growth was attained. There was no significant enhancement of neutrophil killing when TNF or GM/CSF or both were added to either Babesia spp. Addition of TNF or GM/CSF or both substances (without neutrophils) resulted in an increase in growth of B. bovis and B. bigemina. For B. bovis, the group that contained neutrophils only and the group that contained neutrophils and TNF resulted in significantly higher growth inhibitions than the treatment group which contained neutrophils and GM/CSF or the group that contained neutrophils, TNF, and GM/CSF. No significant differences in inhibition were observed for the same treatment groups between B. bovis and B. bigemina. PMID- 1413451 TI - Development of ELISAs based on recombinant antigens for the detection of Toxoplasma gondii-specific antibodies in sheep and cats. AB - ELISAs using recombinant parasite polypeptides as antigens were developed to measure Toxoplasma gondii-specific antibodies in the sera of sheep and cats. Compared with an ELISA based on traditional parasite antigen, the ELISA for sheep sera had a sensitivity of 79% and a negative predictive value of 80%, and the ELISA for cat sera had a sensitivity of 100% and a negative predictive value of 100%. Both ELISAs had specificities of 100% and positive predictive values of 100%. These ELISAs appear to be a useful cost-effective alternative to ELISAs based on traditional parasite antigen for the measurement of T. gondii-specific antibodies in the sera of sheep and cats. PMID- 1413452 TI - Effects of infection with Trypanosoma brucei brucei on different trimesters of pregnancy in ewes. AB - The effects of Trypanosoma brucei brucei infection during the first, second or third trimesters of pregnancy in 13 ewes were studied. All infected ewes were anaemic with the anaemia being most severe, moderate and least in ewes infected in the second, third and first trimesters, respectively. Weight loss occurred in all infected ewes but was most severe in ewes infected in the third trimester. Three of the four ewes infected in the first trimester died without aborting while one aborted and later died. Of the four ewes infected in the second trimester, three died without aborting while one lambed and later died. In the third trimester ewes, one aborted, two lambed and all three later died while one died without aborting. None of the lambs was viable. The control ewe lambed normally. The infection resulted in 16.7% abortion, 100% death and 33.3% neonatal deaths. This study demonstrates that T. brucei brucei has a devastating effect on pregnancy irrespective of the trimester of infection. PMID- 1413453 TI - Experiments on anthelmintic control of Fasciola hepatica in Brazil. AB - Two separate field trials involving naturally infected cattle were carried out on two farms known to have a history of Fasciola hepatica infection. On the first farm, 15 animals per group were allocated as follows: G1, triclabendazole (TCBZ) four times a year; G2, TCBZ twice a year (May and September); G3, untreated control. All groups grazed together and after 3.5 years the animals were slaughtered and their livers examined by federal meat inspectors who condemned 100% of livers in G3 and 8.3% in G2 owing to the presence of lesions of fasciolosis. In G1 no livers were condemned. Significant differences in weight gains were not detected and fluke counts remained at low levels in the treated groups. Also, in the control group, egg counts started to decrease when animals were 2 years old. On the second farm, groups of 20 animals were treated as follows: G1, TCBZ three times a year (May, September and December); G2, TCBZ twice a year (May and September); G3, nitroxynil twice a year (May and September); G4, rafoxanide twice a year (May and September); G5, untreated controls. All animals were weighed and faecal samples examined at approximately 28-day intervals. During the period of the study, larger weight gains were detected in the TCBZ treated groups than in the others. TCBZ treatment kept F. hepatica egg counts at a lower level for longer periods than the other drugs and significant differences in weight gains were only obtained between the group receiving TCBZ three times a year and the control group. PMID- 1413454 TI - The purification and characterization of a cysteine protease of Fasciola gigantica adult worms. AB - A 26-28 kDa protease was isolated from Fasciola gigantica adult worms by a two stage purification process of column chromatography in a Sephacryl S-200 column and affinity chromatography in an L-phenylalanine-agarose column. This protease is a cysteine (thiol) proteinase with an optimum pH of 4.5 and is not inhibited by anti F. gigantica immunoglobulin G. The enzyme was inhibited by protease inhibitors known to inhibit cysteine proteases but not by metallo-, aspartate or serine protease inhibitors. The effect of several protease inhibitors and anti-F, gigantica IgG was also assessed on the total proteolytic activity of F. gigantica. There appears to be a preponderance of cysteine protease activity in F. gigantica and there was a significant inhibition of total proteolytic activity by anti-F. gigantica IgG. PMID- 1413455 TI - Frequency distribution of Echinococcus granulosus in dog populations in the Xinjiang Uygur Autonomous Region, China. AB - Age-prevalence and age-intensity data of Echinococcus granulosus in dog populations were collected in four counties in the Xinjiang Uygur Autonomous Region, People's Republic of China. The frequency distribution of the parasite per dog was adequately described by the negative binomial model, with parameter k being 0.0571. The mathematical model of the life cycle of E. granulosus constructed by Roberts et al. (1986--Parasitology, Vol. 92, pages 621-641) was used to estimate the epidemiologic parameters of E. granulosus in Xinjiang. This model showed that the prevailing infection pressure on dogs was 0.4560 infectious insults year-1 and the mean length of an infection was 1.4975 years. The effect of acquired immunity on the prevalence of E. granulosus in dogs was considered to be insignificant. PMID- 1413456 TI - Precipitin response of the mitogen produced by Strongylus vulgaris arterial larvae. AB - The precipitin response of the mitogen produced by Strongylus vulgaris arterial larvae was investigated. IgG (T) from the sera of horses naturally infected with S. vulgaris adults and arterial larvae recognised the presence of two antigenic components of the mitogenic fractions. The results obtained seem to confirm that these antigens are immunogenic in stimulating the production of increased levels of IgG(T) in infected animals, and showed that the procedures could be used as immunological tools in the diagnosis of S. vulgaris infection. PMID- 1413457 TI - Anthelmintic activity of paraherquamide in calves. AB - Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and Penicillium charlesii, was tested against the adult stages of nine common gastrointestinal and lung nematodes of calves at single, oral dosages of 0.5, 1.0, 2.0 or 4.0 mg kg-1. At dosages 1.0-4.0 mg kg-1 there was 95% or more removal of Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora, Nematodirus helvetianus, Oesophagostomum radiatum, and Dictyocaulus viviparus. Cooperia punctata, the dosage-limiting species, was virtually unaffected by any dosage except the highest, which produced an efficacy of 89%. The 0.5 mg kg-1 dosage was 95% or more efficacious against H. placei, O. ostertagi, C. oncophora, and D. viviparus, but weaknesses were evident against the other five species. No adverse reaction was observe in any calf. PMID- 1413459 TI - The epizootiology of gastrointestinal nematodes of cattle in selected areas of Oregon. AB - A study was initiated to (1) determine species of gastrointestinal nematodes present in cattle in selected areas of Oregon, (2) examine seasonal abundance of these nematodes as an indicator of periods of transmission, and (3) determine when developmental inhibition occurs in the major genera of nematodes encountered. Four study sites were chosen: Corvallis, Langlois, near Fort Rock, and southeast of Klamath Falls on the Oregon-California border. Eight sets of three to four tracer calves each were introduced onto pasture at each site over a 2 year period with time of turn out onto pasture corresponding to late spring, mid-summer, late fall and late winter. At Corvallis, a distinct seasonality in parasite transmission was evident, peaking during the fall and winter. At Langlois, transmission was fairly constant throughout the year. No discernible patterns were evident at either Klamath Falls or Fort Rock. Eight nematode genera were found during the study. Ostertagia, Cooperia, Nematodirus and Trichostrongylus were present at all study sites and were the most common genera at each. Trichuris was found at all sites except Klamath Falls. Oesophagostomum was present in tracers only from Langlois and Corvallis while Haemonchus was found only at Klamath Falls and Fort Rock. Capillaria was only present at Klamath Falls. Where possible, specific transmission patterns for Nematodirus, Cooperia, and Ostertagia were determined for each site. Nematodirus was transmitted fairly steadily at both Langlois and Corvallis but was quite variable at Fort Rock. Developmental arrest was detected in this genus at all study sites during the fall and/or winter. Cooperia exhibited the most seasonally defined pattern of transmission, peaking during the fall and winter at Langlois, Corvallis and Klamath Falls. Hypobiotic larvae of Cooperia were present during the fall and/or winter only at Langlois and Corvallis. Peak transmission of Ostertagia at Langlois and Corvallis occurred during the fall and winter. At Fort Rock, transmission was lowest in the fall and increased in the winter. Hypobiotic larvae were evident in the fall and winter at Corvallis, Fort Rock and Klamath Falls. These data suggest Type II ostertagiasis may occur in late winter through spring in these areas. Hypobiotic larvae of Ostertagia were not detected at Langlois. The lack of appropriate environmental stimuli is one possible explanation for the apparent lack of hypobiosis at that site. PMID- 1413458 TI - Effect of fenbendazole and ivermectin on development of strongylate nematode eggs and larvae in calf feces. AB - Thirty-nine weaned steer calves (mean weight 284 kg) were maintained under dry lot conditions and assigned (based on fecal nematode egg count) to one of three treatment groups of 13 animals each as follows: control (no treatment), fenbendazole (5 mg kg-1), and ivermectin (0.2 mg kg-1). Fecal samples were collected 12 h before treatment, at treatment, and 12, 24, 48 and 72 h after treatment for determination of nematode eggs per gram, and (after culture) infective larvae per gram and population distribution. The effect of treatment on egg development was observed in feces collected 12 and 24 h after treatment. There was essentially no difference in efficacy, based on egg counts, of fenbendazole and ivermectin. Egg count was reduced 100% by both anthelmintics at 72 h after treatment. Viability, based on percent of eggs reaching the infective larval stage, of developing stages at 12, 24, and 48 h after fenbendazole treatment was 0.1%, 1.1%, and 0%; after ivermectin treatment the corresponding values were 23.7%, 30.1%, and 28.6%, respectively. Fenbendazole treatment resulted in little or no development of eggs and/or larvae in feces deposited 12 and 24 h after treatment, whereas development proceeded normally (compared with the control group) in ivermectin treated feces. Population distribution of infective larvae was predominantly Haemonchus and Cooperia with some Ostertagia and Oesophagostomum. PMID- 1413460 TI - Efficacy of Cydectin moxidectin 1% injectable against experimental infections of Dictyocaulus viviparus and Bunostomum phlebotomum superimposed on natural gastrointestinal infections in calves. AB - Twenty male Holstein calves averaging 105 kg in weight and naturally infected with gastrointestinal nematodes and small numbers of lungworm and hookworm, were given experimental infections with the two latter species to provide adult and larval stages for anthelmintic evaluation. Following random allotment, one group of 10 calves was injected subcutaneously with moxidectin at a dosage of 0.2 mg kg 1 of body weight. A second group of 10 was injected subcutaneously with unmedicated blank vehicle at a dosage of 1 ml per 50 kg of body weight. Fecal samples were examined before treatment and at 7 and 13 days after treatment. The 20 calves were necropsied for worm recovery at 13 and 14 days after treatment. All calves were positive for lungworm and hookworm on the treatment date. Treatment was 100% effective in elimination of hookworm eggs and lungworm larvae and 99.9% in reducing total egg counts at both 7 and 13 days after treatment. Moxidectin was 100% effective (P less than 0.01) in eliminating the following 11 species of nematodes. Dictyocaulus viviparus mature and immature adults (E5), Bunostomum phlebotomum adults and L4, Ostertagia ostertagi adults and early L4, Ostertagia lyrata adult males, Haemonchus placei adults. Trichostrongylus axei adults, Cooperia spp., including Cooperia punctata, Cooperia spatulata, and Cooperia pectinata adults, Oesophagostomum radiatum adults and Trichuris discolor adults. No adverse reactions to moxidectin treatment were observed. PMID- 1413462 TI - Exfoliative colpocytology: a method for the diagnosis of Capuchin monkey filariasis? AB - During vaginal fluid examinations (Papanicolaou) to study the physiological sexual cycle of Cebus sp., abundant Dipetalonema gracile microfilariae (110-160 microns x 4-5 microns, without a sheath) were encountered in the genital fluid, but not in peripheral blood. Considering the great difficulty in diagnosing this obscure parasitosis, exfoliative colpocytology was found to be an efficient diagnostic. PMID- 1413461 TI - Influence of exposure period and management methods on the effectiveness of chickens as predators of ticks infesting cattle. AB - Experiments undertaken on Rusinga Island, Kenya, indicated that Rhipicephalus appendiculatus (Neumann) was the predominant tick consumed on tick-infested cattle by chickens, followed by Amblyomma variegatum (Fabricius), Boophilus decoloratus (Koch) and Rhipicephalus evertsi evertsi (Neumann). The number of ticks consumed by chickens released with cattle in a 3 h release period was not significantly different from ticks consumed in a 4 h release period. In a free management system, chickens 1-3 months of age consumed more ticks than older ones; in a confined management system however, chickens 4-6 months of age consumed more ticks than younger birds. Although the numbers of ticks consumed by local and exotic breeds of chickens were not significantly different, a period of 8-10 weeks was necessary for the exotic breeds to become behaviorally adapted to tick predation on cattle. Local chickens bred in environments where cattle were absent took a shorter period of 4-6 weeks to adapt. It was concluded that the relatively large number of ticks consumed by each chicken during the 3 or 4 h release period is an indication that a good reduction of ticks on cattle can be achieved through tick predation by chickens. The preponderance of R. appendiculatus over other tick species consumed was a reflection of its relative abundance on cattle on the island rather than a selective preference for tick species. PMID- 1413463 TI - Subsidence of an uncemented canine femoral stem. AB - Factors contributing to subsidence were analyzed by radiographic evaluation and mechanical testing of 36 canine cadaver femora during and after insertion of an uncemented porous-coated femoral stem and by radiographic evaluation of 35 canine total hip arthroplasties. Mean percentage of canal fill in immediate postoperative radiographs, and percentage of canal fill at midimplant and distal implant locations, were accurate predictors of subsidence. Force required to implant the femoral stem was strongly correlated with force required for implant subsidence. Femoral morphology and percentage of canal fill at the middle and distal sites were accurate predictors of subsidence. Implants in femora with a stovepipe morphology (canal flare index less than or equal to 1.8) were six times more likely to subside than implants in femora that had a normal appearance (canal flare index 1.8 to 2.5), and 72 times more likely to subside than implants in champagne-fluted femora (canal flare index greater than or equal to 2.5). Femora with more than 85% mean, middle, or distal canal fill were less likely to subside. PMID- 1413464 TI - Effect of sagittal plane positioning errors on measurement of the angle of inclination in dogs. AB - Angles of inclination were calculated from ventrodorsal (VD) and caudocranial horizontal beam (CaCrHB) radiographs of 17 anesthetized dogs, and from radiographs of left femurs of the same dogs positioned 0 degree, 10 degrees, 15 degrees, and 20 degrees from the cassette in the sagittal plane. Angles of inclination also were measured directly from radiographs of the bones rotated to correct for anteversion. Calculated angles of inclination from the bones at 10 degrees, 15 degrees, and 20 degrees from the cassette were significantly different from the 0 degree values obtained by calculation and direct measurement. Inclination angles from live dogs were consistently larger than those from 0 degree bones. Differences between angles of inclination calculated from VD and CaCrHB radiographs of live dogs were not significant. PMID- 1413466 TI - Use of a retained urethral catheter in three dogs with prostatic neoplasia. AB - Percutaneous nephrostomy catheters modified by cutting off the tubing connectors were implanted in three dogs with prostatic neoplasia to relieve or prevent stranguria. One catheter was implanted with a guide wire through a perineal urethrotomy, and two catheters were implanted via celiotomy and cystotomy. Morbidity and complications were minimal. Inflammation of the abdominal incision was present from day 4 to day 8 in the dogs with celiotomy. Urinary incontinence was continuous in one dog and intermittent in two dogs. Hematuria occurred in two dogs. The retained urethral catheter was a suitable palliative treatment for urethral obstruction in three dogs with prostatic neoplasia. PMID- 1413465 TI - Hemimaxillectomy for the treatment of oral tumors in 69 dogs. AB - Hemimaxillectomy was performed in 69 dogs for the treatment of benign or malignant maxillary tumors. Eighteen dogs with ameloblastomas had a median disease-free interval of 21.5 months (range, 1 to 76 months), with a 72% 1-year survival time. There was recurrence in three dogs, with metastasis after malignant transformation in one of them. Based on calculated survival curves, seven dogs with squamous cell carcinoma had a median survival time of 19.2 months (range, 2 to 24 months), with a 57% 1-year survival time. There was local recurrence in two dogs. Twenty-three dogs with melanoma had a median survival time of 9.1 months (range, 1 to 46 months), and a 27% 1-year survival time. Twelve dogs died or were euthanatized because of recurrence or metastases. Fifteen dogs with fibrosarcoma had a median survival time of 12.2 months. Eight dogs died or were euthanatized because of recurrence or metastases. Six dogs with osteosarcoma had a median survival time of 4.6 months (range, 1 to 12.5 months), with a 17% 1-year survival time. Five dogs died or were euthanatized for recurrence or metastases. Tumor size or location and type of partial maxillectomy performed did not affect survival. PMID- 1413467 TI - Thermal injury by in vitro incision of equine skin with electrosurgery, radiosurgery, and a carbon dioxide laser. AB - Freshly harvested equine skin incised with an electrosurgical unit, a radiosurgical device, or a carbon dioxide (CO2) laser was examined by light microscopy to determine the extent of thermal injury caused by each instrument. There was no significant difference between the thermal injury caused by the electrosurgical unit in the pure-cut mode and the CO2 laser in the superpulse mode, or between the electrosurgical unit and the radiosurgical device in the fully filtered cut mode. However, thermal injury caused by the CO2 laser was significantly less than that caused by the radiosurgical device. The amount of thermal injury in this in vitro study was similar to that found in vivo with other species. PMID- 1413468 TI - The effect of CO2 laser neurectomy on neuroma formation and axonal regeneration. AB - In an attempt to prevent neuroma formation and digital reinnervation after sharp palmar digital neurectomy in 10 adult horses with navicular disease, 18,426 W/cm2 of CO2 laser energy was applied to the proximal nerve stump. Clinical follow-up was 4 to 23 months. In two horses, palmar digital nerve biopsies were taken at month 4 (four nerves) and month 7 (two nerves). Nine horses were sound immediately and at all follow-up examinations. None had clinical evidence of painful neuroma or digital reinnervation. Histologically, there was minimal scar tissue at the surgical site; axonal sprouts were comingled with fibrous tissue. PMID- 1413469 TI - Holding power of cortical screws after power tapping and hand tapping. AB - Paired equine third metacarpal bones were drilled and tapped for 4.5 mm and 5.5 mm cortical screws. Tapping was done by hand or with an air-driven reversible orthopedic drill. Screws were inserted and subjected to extraction forces to failure of the osseous threads or the screws. There was no difference in holding power of either screw size between hand-tapped and power-tapped holes. PMID- 1413470 TI - Regional limb perfusion for antibiotic treatment of experimentally induced septic arthritis. AB - Septic arthritis was induced in one antebrachiocarpal joint of seven horses by the intra-articular injection of 1 mL Staphylococcus aureus suspension containing a mean of 10(5) colony-forming units. Twenty-four hours after inoculation, four horses were treated by regional perfusion with 1 g of gentamicin sulfate, and three horses received 2.2 mg/kg gentamicin sulfate intravenously (IV) every 6 hours. Synovial fluid was collected for culture and cytology at regular intervals, and the synovial membranes were collected for culture and histologic examination at euthanasia 24 hours after the first treatment. Gentamicin concentration in the septic synovial fluid after three successful perfusions was 221.2 +/- 71.4 (SD) micrograms/mL; after gentamicin IV, it was 7.6 +/- 1.6 (SD) micrograms/mL. The mean leukocyte count in the inoculated joints decreased significantly by hour 24 in the successfully perfused joints. Terminal bacterial cultures of synovial fluid and synovial membranes were negative in two horses with successfully perfused joints. S. aureus was isolated from the infected joints in all three horses treated with gentamicin IV. PMID- 1413471 TI - Use of an ecraseur for ovariohysterectomy in mares. AB - Ovariohysterectomy was performed in 20 mares at three stages of estrus. An ecraseur was used to severe the ovarian branch of the ovarian artery and vein and the ovarian suspensory ligament en masse. All other vessels supplying the ovaries and uterus were doubly ligated and transected. All mares survived. Complications were intraoperative hemorrhage in three mares, postoperative vaginal bleeding in two mares, and a hematoma in the remnant of the broad ligament in one mare. No adhesions between the uterine stump or remnants of the broad ligament and abdominal structures were detected by palpation per rectum. PMID- 1413472 TI - A one-stage repair of third-degree perineal lacerations and rectovestibular fistulae in 17 mares. AB - Third-degree perineal lacerations or rectovestibular fistulae in 17 mares were repaired surgically by a one-stage method. Primary healing occurred in 14 mares; there were one complete dehiscence and two partial dehiscences with fistula formation. Twelve of 13 mares that were bred became pregnant; nine carried foals to term and two are still pregnant. Two mares have each produced one unthrifty foal. One mare repeatedly aborts in the first trimester. Four mares have produced several healthy foals with no further problems. One mare suffered further perineal trauma while foaling. PMID- 1413473 TI - Cardiovascular and pulmonary effects of atropine reversal of oxymorphone-induced bradycardia in dogs. AB - Oxymorphone was administered intravenously (IV) to 10 dogs (0.4 mg/kg initial dose followed by 0.2 mg/kg three times at 20-minute intervals). Four hours after the last dose of oxymorphone, heart rates were less than 60 bpm in six dogs. After atropine (0.01 mg/kg IV) was administered, heart rate decreased in five dogs and sinus arrhythmia or second degree heart block occurred in four of them. A second injection of atropine (0.01 mg/kg IV) was administered 5 minutes after the first and the heart rates increased to more than 100 bpm in all six dogs. Ten minutes after the second dose of atropine, heart rate, cardiac output, left ventricular minute work, venous admixture, and oxygen transport were significantly increased, whereas stroke volume, central venous pressure, systemic vascular resistance, and oxygen extraction ratio were significantly decreased from pre-atropine values. The PaCO2 increased and the PaO2 decreased but not significantly. The oxymorphone-induced bradycardia did not produce any overtly detrimental effects in these healthy dogs. Atropine reversed the bradycardia and improved measured cardiovascular parameters. PMID- 1413474 TI - A clinical comparison of oxymorphone-acepromazine and butorphanol-acepromazine sedation in dogs. AB - Oxymorphone (0.2 mg/kg, maximum 4.5 mg) or butorphanol (0.2 mg/kg, maximum 4.5 mg), with acepromazine (0.05 mg/kg) and atropine (0.02 mg/kg), was administered intravenously to 106 healthy dogs undergoing radiographic examination of the pelvis. The dogs were returned to their owners after the examination and opioid reversal with naloxone (0.02 mg/kg intravenously, maximum 0.4 mg). Questionnaires were completed by the radiology staff and owners of the dogs, and results were coded by one person, all of whom were unaware of the treatment used. There was a lower incidence of temporary excitement upon injection and less panting in dogs sedated with butorphanol than with oxymorphone. There were no significant differences in degree of sedation, response to noise or manipulation, vocalization, defecation, heart rate, reversibility, sedation after reversal, or personality. Both forms of chemical restraint were satisfactory for radiographic examination of the pelvis, with no significant side effects in healthy dogs. PMID- 1413475 TI - Bile acid fractionations by high-performance liquid chromatography in equine liver disease. AB - Serum bile acids were fractionated by high-performance liquid chromatography (HPLC) in 13 control and 8 cases of liver disease in horses. The severity and type of liver injury was determined by histopathological examination of biopsy and/or necropsy specimens. The total serum bile acids (tSBA) were determined in these horses by an enzymatic method (SBA-EA) and by summation of the bile acids (SBA-LC) as fractionated by the HPLC. The SBA-LC were generally higher than the SBA-EA in both the controls and liver disease and they did not parallel each other. The primary bile acids, total cholates and total chenodeoxycholates accounted for most of the tSBA increases in liver disease. There was a shift in profile from taurocholate to free (unconjugated) cholate in direct relation to the severity of the liver injury. Among the secondary bile acids, total deoxycholates and total taurodeoxycholates increased at random. The pattern of the SBA profile in relation to the severity of the liver disease suggested that hepatocellular excretion is the most sensitive step in the enterohepatic circulation of the bile acids. PMID- 1413476 TI - Plasma and red cell cholinesterase concentrations in guinea-fowl (Numuida meleagris) and Nigerian domestic fowl (Gallus domesticus). PMID- 1413477 TI - Co-migrating and shared antigens of selected Pasteurella haemolytica untypable strains. AB - Bacterial cell envelope preparations from eight untypable strains of Pasteurella haemolytica were compared by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunoblotting with rabbit antisera prepared against the eight untypable strains (one untypable strain per rabbit) and with cattle antisera prepared against P. haemolytica serotypes 1, 2, 5, 6, 9 and against one heterologous untypable strain. Numerous comigrating and shared antigens were recognized by the eight rabbit antisera and the P. haemolytica serotype cattle antisera. Comigrating antigens at 43 and 30 kilodaltons (kDa) were recognized by all eight rabbit antisera. Shared antigens, detected by all eight rabbit antisera when reacting against P. haemolytica serotype 1, were recognized at 43, 32, 30, 20 and 15 kDa. PMID- 1413479 TI - Multiple anthelmintic resistance in a field strain of Haemonchus contortus in goats. PMID- 1413478 TI - The effect of including anti-Ig sera in the haemagglutination inhibition test for Mycoplasma gallisepticum. AB - Addition of anti-immunoglobulin M (anti-IgM), G (anti-IgG) and A (anti-IgA) sera to the haemagglutination-inhibition (HI) test (anti-Ig HI test) for Mycoplasma gallisepticum resulted in 2- to 8-fold increases in the HI titres. On investigating the anti-Ig HI reaction using IgM and IgG antibodies separated by affinity chromatography, it was confirmed that, in the enhanced HI titres, specificity existed between the chicken Ig classes having antibody activity and the antisera used in the test. Four days after inoculation of M. gallisepticum, the anti-Ig HI reaction was markedly enhanced by anti-IgM antiserum in the intravenously inoculated chickens and by anti-IgA serum in the nasally inoculated chickens. Ten days after inoculation of M. gallisepticum marked enhancement of the reaction was produced by anti-IgG serum in both intravenously and nasally inoculated chickens, but the enhancement of the anti-Ig HI reaction diminished from the second week after inoculation. PMID- 1413480 TI - Glutathione transferase activity in livers from lambs of three different breeds of Norwegian sheep, and its possible relationship to alveld. PMID- 1413482 TI - Pharmacokinetics following a single intravenous administration and a dosage regimen for sulfadoxine in buffalo calves (Bubalus bubalis). PMID- 1413481 TI - The effect of central sympathectomy by 6-hydroxydopamine (6-OHDA) on the response to morphine in conscious sheep. AB - When morphine, an opioid mu-agonist, was administered in vivo into the third cerebral ventricle (ICV) of conscious sheep at 20 and 40 micrograms/kg body weight, it caused psychomotor excitability for 2-3 h and a significant decrease in the reticuloruminal frequency for 45 min and in the mean amplitude of the primary contractions for 65 min. From 60 min after infusion, the same doses of morphine caused a significant increase in the average amplitude of the contractions for 45 min. This suggests that an inhibitory mu-opioid acceptor is involved in the central control of forestomach motility and general behaviour in sheep. All the effects of morphine were completely prevented by pretreatment with 18.2 micrograms/kg body weight 6-OHDA ICV. These results suggest that both morphine-induced inhibition of rumen motility and psychomotor excitability are due to central noradrenergic descending system activation. The exact location of the noradrenergic system remains to be determined. PMID- 1413483 TI - The comparative haematology of cross-bred and indigenous east African goats of Tanzania and breeds reared in Denmark. AB - Erythrocyte counts, haematocrit, haemoglobin concentration, red blood cell indices, total and differential leukocyte counts were determined in 202 cross bred and 14 indigenous East African goats aged 6-12 months and also in 59 Norwegian dairy goats, of which 24 were 15-45 days old, 8 were 8 months old and 27 were over 3 years and pregnant. These were reared in Tanzania. Comparisons were made with 24 Dwarf and 57 Danish Landrace goats at 6-12 months of age and 76 adult pregnant Danish Landrace goats reared in Denmark. The purpose was to determine reference ranges for cross-bred and indigenous East African goats and to compare these with those of other breeds. The haemoglobin concentration, haematocrit, erythrocyte and white blood cells were lowest in the Norwegian kids. The highest values were observed in 6-12-month-old goats in all the breeds, whereafter they decreased to relatively constant adult levels. The mean corpuscular volumes were highest in kids followed by adult pregnant Norwegian and Danish Landrace goats, and lowest in 6-12 months old goats. East African and cross-bred goats had the smallest mean corpuscular volumes. The haemoglobin concentration, erythrocyte and leukocyte counts were highest in indigenous East African, followed by young Norwegian and cross-bred goats. The mean corpuscular haemoglobin concentration was highest in the cross-breds, while the mean corpuscular haemoglobin was higher in pregnant than in other goats. The age and breed differences were statistically significant. PMID- 1413484 TI - Biochemical and physiological parameters and estimated work output in draught horses pulling loads for long periods. AB - A study was undertaken in five draught horses of 648 +/- 33 kg body weight to find the effects of continuously pulling loads on their cardiovascular, respiratory and metabolic responses. A cart equipped with an odometer, for measuring distance, and a hydraulic dynamometer, for measuring draught force, was used. Heart and respiration rates and rectal temperatures were recorded. Blood samples for measuring arterial and venous pH and blood gases, haemoglobin, glucose and lactic acid concentrations and the serum activity of the enzymes creatine phosphokinase (CK), lactate dehydrogenase, aspartate aminotransferase and alkaline phosphatase were taken before exercise and immediately after each journey (morning and afternoon) of the daily work. Draught exercise, with loads which generated forces of between 0.57 and 0.59 kN, at speeds of 1.60 to 2.11 m/s, for 8 h daily for five consecutive days, with resting intervals of 10 min each hour, was well tolerated. Exercise tolerance was evaluated from the recovery from the changes observed in the biochemical and physiological parameters induced by the work. The analysis of these showed that, when the horses were subjected to prolonged periods of resting, their loss of fitness for work was shown by significant increases in the serum activity of muscle-derived enzymes and in blood lactate concentrations during the first day of work. However, over the following days the horses adapted to the work, so that the decreases in serum enzyme activities and blood lactate concentrations were reduced. Since similar observations have been described for racehorses, the determination of blood lactate concentrations and the serum activities of muscle-derived enzymes, specifically CK, seem to be good indicators of fitness in draught horses. PMID- 1413485 TI - Effect of ageing and malnutrition on rat myocardium. I. The myocyte. AB - The effects of ageing and starvation on the rat myocardium were studied by morphometric methods. Since cardiac muscle is a tissue with a high level of anisotropy, methods based on the concept of vertical planes were used to describe quantitative alterations in the rat myocyte both at the cellular and ultrastructural level. During starvation rapid and important changes were noted, particularly in the transverse dimension of cells and organelles. The most striking change, however, was the immediate dilatation of the myocyte T-system, reflecting an adaptive interaction between the intra- and extracellular environment. At the same time exocytosis of intracellular components into the extracellular space of the T-system was observed. The ratio of mitochondria to myofibrils decreased progressively during starvation. Such a decrease, in general, may reach a point when cellular energy supply becomes compromised. A comparison between different regions of the heart showed no differences and it can be concluded that the morphological changes during starvation are the same, and equally distributed, in both ventricles. The changes described in the aged rat heart point in the direction of a hypertrophy of the aged myocyte. This leads to a lower ratio between surface and volume which finds its representation at the subcellular level in a more spherical shape of nuclei and mitochondria. Unlike what is seen in malnutrition, the mitochondrial/myofibril ratio is higher in the older rat. From the morphological point of view, the atrophy of malnutrition and the hypertrophy of ageing are opposed, but in both there is a change in the relationship of the myocyte to its environment which directly influences the substrate exchange capacity. This tends to protect the myocyte in starvation but jeopardizes the older cell. PMID- 1413486 TI - Effect of ageing and malnutrition on rat myocardium. II. The microvasculature. AB - The modulating effects of ageing and malnutrition on rat myocardium were studied morphometrically with respect to the microvasculature. An increase in capillary density together with a decrease in capillary lumen cross-sectional area was noted during starvation. The important changes seen in the myocyte T-system were paralleled by a decreased diffusion distance for oxygen from the capillary lumen to the mitochondrion. The changes described in the aged rat heart point to an altered inter-relationship between parenchyma and vascularization with a lower capillary volume fraction and a greater diffusion distance from the capillary lumen to the mitochondrion; this is caused by hypertrophy of the aged myocyte. This reduction in capacity to exchange substrates is further reduced by the less developed T-system in the older myocyte. PMID- 1413487 TI - Ag-NOR protein distribution correlates with patient survival in stage I endometrial adenocarcinoma. AB - The relationship between argyrophil nucleolar organizer region (Ag-NOR) protein quantity and prognosis was studied in 33 cases of stage I endometrial adenocarcinoma. Ag-NOR protein quantity was measured by image analysis in silver stained sections from paraffin-embedded samples of curettings. Patients had a minimum 10-year follow-up. Only 2 out of 25 patients exhibiting a mean Ag-NOR protein area of less than 3 microns2 died of cancer, whereas 5 of the 8 patients with a mean Ag-NOR protein area of more than 3 microns2 died of the disease. The present results demonstrate that the Ag-NOR protein value is closely related to patient survival in stage I endometrial carcinoma and that it is a reliable prognostic indicator in this type of carcinoma. PMID- 1413489 TI - Cell populations in the lesion of human cutaneous leishmaniasis: a light microscopical, immunohistochemical and ultrastructural study. AB - To characterize the in situ cellular immune response in localized cutaneous leishmaniasis (LCL), the authors studied frozen skin biopsies from 50 patients with LCL due to Leishmania braziliensis guyanensis. A panel of 31 monoclonal antibodies was used, which defined the number and distribution of inflammatory cell subsets. Skin inflammatory infiltrates were composed of T cells (with a local CD4/CD8 ratio of 1.05 +/- 0.7 vs 1.48 +/- 0.3 in peripheral blood), macrophages and a smaller number of B cells, natural killer cells and granulocytes. Most of the T cells expressed activation markers (interleukin-2 and transferrin receptors, HLA-DR+) and an increase in T-cell-receptor gamma delta expression was noted. Analysis of the CD4+ subpopulations with newly available reagents showed that helper T cells (CD4+CD45RO+) exceeded the suppressor/inducer subset (CD4+CD45RA+) by 1.4:1. There were no differences between local immune variables from patients with primary infection (45 patients) and those with recurrence (5). In 7 patients, biopsies were analysed before and 1 month after specific treatment, and did not show significant differences except for a small increase of dermal CD1a+ (Langerhans) cells/mm2. The observed pattern of cellular skin infiltration suggests an immune-mediated tissue injury including T-cell mediated cytotoxicity and delayed hypersensitivity reactions in addition to direct parasitic action. PMID- 1413488 TI - Comparative analysis of p53 protein immunoreactivity in prostatic, lung and breast carcinomas. AB - In this study we analysed the expression of p53 protein in a total of 143 carcinomas immunohistochemically. These consisted of 34 prostatic adenocarcinomas, 59 lung and 50 breast carcinomas. In 28 cases, an average of 2-3 additional sections from different tumour areas were analysed. Forty-nine of the 143 carcinomas (34%) showed typical nuclear immunoreactivity by immunohistochemical staining with the p53 antibody CM-1. Two of the 34 prostatic carcinomas (6%) were p53 positive while 25 of the 59 lung carcinomas (43%) and 22 of the 50 breast carcinomas (44%) showed positivity for p53. By grade: 49% of grade III tumours, 36% of grade II and 5% of grade I tumours were p53 positive. There were significantly more p53-positive cases in grade II-III tumours than in grade I tumours (P = 0.001) when all tumours were taken into account. Further, there were significantly more p53-positive cases in grade III than in grade I-II tumours (P = 0.001). In lung tumours there were significantly more p53-positive cases in grade II-III tumours than in grade I tumours (P = 0.018). Similarly, there were significantly more p53-positive tumours in grade III breast tumours than in grade I-II tumours (P = 0.003). The low incidence of p53 positivity in prostate carcinomas suggests that mutations of the p53 gene are not as frequent in the neoplastic transformation of these tumours as in lung or breast carcinomas. The association of p53 positivity with tumours of higher grade suggests that p53 mutations lead to tumours of a more aggressive type. The analysis of tumours by multiple sections indicates that p53 positivity is not evenly distributed in tumour tissue. Therefore, analysis of additional tumour areas may reveal positivity some cases, which is not evident if only one section is studied. PMID- 1413490 TI - Localization of thromboxane synthase in human tissues by monoclonal antibody Tu 300. AB - Using the monoclonal antibody Tu 300 we localized thromboxane synthase, a secondary enzyme of the arachidonic acid cascade, employing the alkaline phosphatase anti-alkaline phosphatase method and indirect double labelling immunofluorescence in frozen sections of human tissues. Aside from platelets, the source of the antigen, all cells of the mononuclear phagocytic system were positive, including epithelioid cells and associated giant cells, starry sky macrophages, dendritic cells of T-cell areas, Langerhans cells and Kupffer cells. In addition, some epithelial cells such as epithelia of tonsillar crypts, reticular epithelia of the thymic cortex and ductular epithelia in liver, pancreas, female breast and salivary glands showed occasional focal reactivity for thromboxane synthase. We suggest that the mAb Tu 300 is a key marker for the macrophage system and the thromboxane generating system in normal and pathological conditions. It may detect functional activities of as yet unknown significance in some specialized epithelial cells. PMID- 1413491 TI - Immunopathological study of eosinophils in eosinophilic granuloma of bone: evidence for release of three cationic proteins and subsequent uptake in macrophages. AB - Eosinophils from two patients with eosinophilic granuloma of bone (EGB) were studied by combined immunohistochemical and immuno-ultrastructural methods with antibodies directed against three eosinophil granule proteins: major basic protein, eosinophil cationic protein, and eosinophil peroxidase. Immunohistostaining showed the presence and distribution of large numbers of eosinophils in the granuloma. Immuno-ultrastructural methods showed alterations of eosinophil fine structure associated with some steps in the release of granule proteins. No granule extrusion was seen, but rather cationic proteins diffused within cytoplasmic tubulo-vesicular structures. Furthermore, the three granule proteins were found within phagolysosomes of surrounding macrophages, suggesting an interaction between eosinophils and phagocytic cells at the destructive stage of EGB. PMID- 1413493 TI - Abnormal p53 immunoreactivity and prognosis in node-negative breast carcinomas with long-term follow-up. AB - The expression of the p53 gene product was investigated immunocytochemically in a retrospective series of 164 formalin-fixed paraffin-embedded invasive breast carcinomas with pathologically proven negative lymph nodes. Overall, 78 tumors (48%) showed a variable degree of p53 immunoreactivity. Among these, 38 cases were low expressors (1-10% p53 immunoreactive tumor cells), 21 moderate expressors (10-50% immunoreactive cells) and 19 high expressors (> 50% immunoreactive cells). Abnormal p53 expression correlated significantly with tumor size, histological and nuclear grade, DNA ploidy, mitotic rate and proliferation index, and with the lack of estrogen receptors. Disease-free and adjusted survival analysis of the 124 node-negative patients with long term (more than 10 years) follow-up, however, did not reveal an independent prognostic role for p53 expression. These data suggest that the evaluation of p53 immunoreactivity may only play a role in a multiparametric prognostic assessment of node-negative breast carcinoma. PMID- 1413492 TI - Composition and classification of human atherosclerotic lesions. AB - Human atherosclerotic disease can be resolved into eight types of lesion, each characterized by its composition and structure and the absence or degree of intimal injury. The eight types have been arranged in the sequence in which they may progress in complexity from the initial change in childhood or youth to the clinical endpoints in older persons. While lesions at first increase primarily by intra- and extracellular accumulation of lipid, this in itself rarely accounts for symptomatic obstruction. Lipidic lesions become symptomatic primarily by means of successively superimposed deposits of thrombotic material. Non homogeneity of hemodynamic forces within the length of an artery account for local differences in intima thickness (adaptive intimal thickening) and, in persons with risk factors, differences in susceptibility to lesion formation. According to the degree to which they can accumulate or retain lipid and bring about secondary mechanisms, specific locations of the arterial tree have been designated as atherosclerosis-resistant, atherosclerosis-prone and progression prone. PMID- 1413494 TI - Comparison of various basement membrane components in benign and malignant peripheral nerve tumours. AB - Immunohistochemical methods were used to analyse benign and malignant tumours of peripheral nerve tissue. We tested for the distribution of basement membrane (BM) components collagen IV, laminin, heparan sulphate proteoglycan, fibronectin, for S100 protein and for the presence of interstitial collagens III and V. Laminin was generally noted in association with Schwann cells, but collagen IV occurred with perineural cells. When tested for BM components, fibroblasts were notably non-reactive except for fibronectin. Three specific area-dependent BM patterns were observed in the benign tumours: (a) Schwann cell-like, in fascicular areas (Antoni A areas of schwannoma, central fibrous bundles of plexiform neurofibromas and central areas of cutaneous neurofibroma), (b) perineural cell-like (capsular structures of schwannoma) and (c) fibroblast-like (myxoid and fibrously transformed areas). Most malignant tissues showed a variably fragmentary focal deposition of laminin. Other BM components were present only in well differentiated areas. Poorly differentiated tumours demonstrated fibronectin reactivity alone. Our results provide evidence that the specific staining pattern for BM components helps to differentiate the various cellular proliferations in neurogenic tumours. Schwann cells are not only distinguishable from perineural cells by S100 protein staining, but also by their specific BM staining. In addition, perineural cells can be separated from fibroblasts, which do not express BM material. The "tropism" of laminin in normal nerves and benign neural tumours--which persists in neurogenic sarcomas--indicates preferential Schwann cell differentiation in these cells. PMID- 1413496 TI - Eccrine gland involvement in Krabbe's disease. AB - Lysosomal storage inclusions were observed in skin eccrine gland secretory and myoepithelial cells in three cases of Krabbe's disease. In addition to storage there were numerous degenerative changes, occasionally resulting in cell necrosis. These findings suggest a generalized nature of the storage process in this lysosomal enzymopathy and point to high galactocerebroside turnover in eccrine gland epithelium. This knowledge may be of value in the biopsy diagnosis of Krabbe's disease. PMID- 1413495 TI - Immunohistology of islet amyloid polypeptide in diabetes mellitus: semi quantitative studies in a post-mortem series. AB - Immunoreactivity for islet amyloid polypeptide (IAPP) in the islets of Langerhans of non-insulin-dependent diabetic patients and non-diabetic patients of a non selected post-mortem series was studied with a new polyclonal IAPP antibody. Out of 133 patients examined, 124 exhibited immunoreactivity for IAPP. Immunoreactivity was localized intra- and extracellularly and was limited to the islets of Langerhans. No extracellular immunoreactivity was observed in amyloid negative cases. Co-localization of insulin and IAPP in the same islet-cells was verified by double staining with monoclonal insulin and polyclonal IAPP antibodies. Of 100 patients with non-insulin-dependent diabetes mellitus (NIDDM) and islet amyloid, 98 exhibited IAPP-positive deposits and 71 exhibited intracellular immunoreactivity. Evaluation of intracellular immunoreactivity and degree of islet amyloid deposition in cases of overt NIDDM revealed an inverse relationship, in that intracellular IAPP immunoreactivity were reduced in patients with developing islet amyloid deposition. Our data are consistent with the hypothesis of primary beta-cell dysfunction leading to amyloid formation, with subsequent disturbance of beta-cell homeostasis. PMID- 1413497 TI - Site-directed mutations in the potyvirus HC-Pro gene affect helper component activity, virus accumulation, and symptom expression in infected tobacco plants. AB - Helper component (HC-Pro) is a virus-encoded nonstructural protein required for aphid transmission of potyviruses. In the tobacco vein mottling virus (TVMV) polyprotein, HC-Pro represents a 457 residue polypeptide from amino acid position 257 to 713. Previous sequence comparison studies have suggested that mutations of one or two specific amino acid residues in the HC-Pro protein might result in loss of aphid transmission activity. To test this hypothesis, the initial targets were the residues corresponding to these specific amino acids, a lys to glu change and an ile to val change at amino acid positions 307 and 482, respectively, of the TVMV polyprotein, as well as the combination of the two. Two additional mutations within the HC-Pro representing dipeptide changes thr-ser to ile-asp and thr-ala to leu-glu at amino acid positions (283/284) and (368/369), respectively, were also tested to further define the effects of mutations in this region on helper component activity. The mutations at positions 482 and (368/369) had no effect on aphid transmission activity, while mutation at position 307 completely abolished the activity. Except for the 482 mutation, all the mutations also affected symptomatology and virus accumulation in infected plants. Due to the very low concentrations of HC-Pro in plants infected with the (283/284) mutant, the effect of this dipeptide change on aphid transmission activity could not be assessed. The majority of the tested mutations fall within a putative zinc finger motif postulated in the cysteine-rich N-terminus of HC-Pro. The possible role of this motif in the potyviruses is further discussed in the light of our present results with TVMV. PMID- 1413498 TI - Myxoma virus M11L ORF encodes a protein for which cell surface localization is critical in manifestation of viral virulence. AB - Myxoma virus (MYX) induces extensive immunosuppression in infected rabbits and is associated with high levels of mortality. The virus encodes multiple gene products designed to circumvent the cellular immune response to the viral infection. Deletion analysis has shown that the M11L open reading frame (ORF) is an important virulence factor which downregulates leukocyte infiltration of MYX induced tumors. To investigate the role of the M11L protein in viral pathogenesis, we sequenced the MYX M11L ORF and showed that the sequence has motifs consistent with a 166-aa class III membrane-spanning molecule possessing a single transmembrane helix near the C-terminus and a 142-aa N-terminal extracellular domain that has six cysteine residues plus two consensus N glycosylation sites. Transcription analysis indicates that M11L is expressed as an early gene, and surface immunofluorescence studies with anti-M11L antibodies reveal that M11L protein is transported to the infected cell surface. Immunoprecipitation analysis of an attenuated viral recombinant, vMYX-GF-delta M11L, indicates that an M11L variant protein with an altered C-terminus is synthesized at about 45% of wild type levels; however, it is not detectable on the cell surface, suggesting that proper M11L function requires localization at the infected cell membrane. We propose that M11L is a virulence factor whose function is to recognize an extracellular ligand essential for the cellular inflammatory response. PMID- 1413499 TI - The nucleotide sequence of adenovirus type 11 early 3 region: comparison of genome type Ad11p and Ad11a. AB - The early 3 region (E3) of two strains (genome type Ad11p and Ad11a) of human adenovirus serotype 11, causing persistent urinary and acute respiratory illnesses, respectively, has been identified and partially sequenced. The sequenced E3 regions of Ad11p and Ad11a were 1980 and 1966 bp long and encoded three complete ORFs, 18.5, 20.3, 20.6k within the Ad11p genome and 18.5, 20.3, 20.2k within the Ad11a genome. The sequence analysis of the 18.5k gene product demonstrated that a transmembrane domain and a cytoplasmic domain of Ad11p, Ad11a, and Ad35 was identical. Ad11p and Ad35 were homologous in the signal sequence. There was one amino acid mismatch between Ad11p and Ad11a, represented by an alanine instead of a proline. The endoplasmic reticulum lumenal domain, which binds to class I MHC, was relatively conserved between Ad11p and Ad11a with the exception of Glu80 and Glu104 in Ad11p, which were replaced by Gln80 and Lys104 in Ad11a. Within the 20.2k protein of Ad11a, the amino acid sequence Thr Thr-Ser-His was deleted from a position immediately upstream the transmembrane region of the Ad11p 20.6k protein. The 9.0k E3 open reading frame (ORF) of Ad3 was deleted in the genomes of Ad11p and Ad11a. It is noteworthy that Ad11p and Ad35 which both cause persistent infection of the urinary tract display a remarkable similarity in several ORFs of the E3 region. PMID- 1413500 TI - Adenovirus transformation revertant resistant to retransformation by E1 but not by SV40-T and HPV16-E7 oncogenes. AB - We have previously described a revertant cell line which expresses a dominant tumor suppressor phenotype to E1 but not to heterologous oncogenes such as c-myc, N-ras, or polyoma middle t (Sircar et al. (1988) Oncogene 3, 725-728). DNA tumor virus oncogenes have been suggested to transform cells via the common mechanism of sequestering the Rb-105 antioncoprotein. This paradigm would predict that our revertant cell line, which is resistant to retransformation by E1a, should also be resistant to the other members of the Rb-105 binding family of oncogenes. To test this hypothesis we transfected the revertant cell line with plasmids bearing SV40-T or the HPV16-E7 oncogenes. Because transformation was obtained by both oncogenes at efficiencies similar to the transformation of a related revertant cell line, the results suggest that the resistance phenotype is specific to E1a. This specificity was further confirmed by cell fusion experiments. PMID- 1413501 TI - The complete nucleotide sequence of pepper mottle virus genomic RNA: comparison of the encoded polyprotein with those of other sequenced potyviruses. AB - The complete nucleotide sequence of a pepper mottle virus isolate from California (PepMoV C) has been determined from cloned viral cDNAs. The PepMoV C genomic RNA is 9640 nucleotides excluding the poly(A) tail and contains a long open reading frame starting at nucleotide 168 and potentially encoding a polyprotein of 3068 amino acids. Comparison of the PepMoV C presumptive polyprotein with those of other sequenced members of the potyvirus group, including tobacco etch virus (TEV), tobacco vein mottling virus (TVMV), plum pox virus (PPV), and potato virus Y (PVY), allowed localization of putative protein cleavage sites. A similar analysis was used to determine the position of conserved viral protein-coding regions along the viral genomic RNA. These analyses confirm previous work indicating that genome organization is conserved among members of the genus Potyvirus. The localization of one PepMoV C gene product, the nuclear inclusion body protein a (NIa protein), was analyzed by expressing PepMoV cDNA deletion clones in bacteria and assaying for appearance of mature-sized coat protein, a cleavage product of the NIa protease. Comparative sequence analyses of the putative PepMoV polyprotein with those of TEV, TVMV, PPV, and PVY served to identify regions of the potyviral polyproteins which have diverged within the genus, as well as highly conserved protein features which may play an important functional role in the potyviral life cycle. PMID- 1413502 TI - Complete nucleotide sequence of the cloned infectious genome of Junonia coenia densovirus reveals an organization unique among parvoviruses. AB - We previously constructed a recombinant plasmid, pBRJ, encompassing an infectious Junonia coenia densovirus (JcDNV) genome (M. Jourdan et al. (1990). Virology 179, 403-409). We report here the complete viral sequence of pBRJ. The genome, 5908 nucleotides (nt) long, consists of an internal unique sequence flanked by long (517 nt) inverted terminal repeats. The first 96 bases of one extremity can fold into a typical Y-shaped hairpin structure. The opposite extremity is incomplete, lacking 88 nt. These terminal structures, similar to those of dependoviruses, human parvovirus B19 and Bombyx mori densovirus (BmDNV), strongly suggest a common mechanism of DNA replication for these parvoviruses. JcDNV genomic organization is unique among parvoviruses in that coding sequences are evenly distributed in the 5' half of both strands. On one strand, the major open reading frame (ORF1) encodes the four structural proteins. On the complementary strand, ORF2, ORF3 (included in ORF2), and ORF4 probably encode nonstructural proteins. JcDNV genome has little DNA homology with vertebrate parvoviruses and surprisingly even less with the two densoviruses presently sequenced. ORF1 contains the highly conserved PGY and G-rich regions and ORF2 the NTP-binding domain common to most structural and to all nonstructural vertebrate parvoviral ORFs, respectively. The single homology between JcDNV and BmDNV is unexpectedly located in JcDNV NTP-binding domain and BmDNV ORF2 assumed to encode structural polypeptides. Only a weak homology exists between JcDNV and Aedes DNV in their NTP-binding domain. PMID- 1413504 TI - Replication capacities of natural and artificial precore stop codon mutants of hepatitis B virus: relevance of pregenome encapsidation signal. AB - The emergence of hepatitis B virus variants unable to express HBe protein during late stage of viral infection may represent an important mechanism of viral persistence. The molecular mechanisms responsible for the elimination of HBe expression are nonsense or frameshift mutations or initiation codon mutations in part of its coding sequence, the precore region. So far only 2 of the 29 precore amino acid codons have been found mutated to stop codons in nature, although a total of 10 codons are convertible to stop codons by single nucleotide changes. Since the HBe-coding sequence is largely overlapped by the pregenome encapsidation signal (epsilon signal), a recently found cis-acting element required for the packaging of pregenomic RNA, the absence of other potential nonsense mutants could result from their impairment of the epsilon signal. Seven such potential stop codon mutants were constructed and tested for replication capacities by transfection into a hepatoma cell line. Five mutants were replication competent, but at levels lower than that of a prevalent natural stop codon mutant. The remaining two mutants were completely defective in DNA replication, which clearly explained why these two mutants are not found in nature. Northern blot analysis revealed wild-type levels of RNA transcription by these two mutants but complete lack of packaged pregenomic RNA. Additional studies lent further support to the importance of the epsilon signal in pregenome encapsidation and suggested relaxed sequence requirements for the computer predicted hexanucleotide bulge region as compared to the hexanucleotide loop of the signal. PMID- 1413505 TI - Transcription dependence of DNA packaging of bacteriophages T3 and T7. AB - T3 and T7 phages package homologous DNA more efficiently than heterologous DNA and recombinant plasmids carrying DNA sequences necessary for DNA packaging (pac sequence). The pac sequence contains a promoter for phage RNA polymerase and transcription from the promoter is necessary for DNA packaging. T3 and T7 RNA polymerases are stringently specific for their own promoters. To examine the relationship between DNA packaging and transcription, we constructed a cleared in vitro system for packaging T3 or T7 DNA containing an ammonium sulfate fractionate of a high-speed supernatant of phage-infected cells. In the system, DNA packaging required GTP and was inhibited by the 3'-deoxy analog of GTP, ATP, or CTP. The DNA packaging activity paralleled the transcriptional activity, assayed by incorporation of [32P]UTP into acid-insoluble material. In the system, homologous DNA was packaged more efficiently than heterologous DNA, but heterologous DNA was packaged as efficiently as homologous DNA by the addition of heterologous phage RNA polymerase, demonstrating that the transcriptional specificity determines the DNA packaging specificity of T3 and T7. PMID- 1413503 TI - Mutational analysis of the coat protein gene of potato virus X: effects on virion morphology and viral pathogenicity. AB - The role of the coat protein of potato virus X (PVX) was investigated by site directed mutation of the coat protein gene. Mutant viruses with in-frame deletions in the 5' end of the coat protein gene were capable of systemically infecting plants, but produced virions with atypical morphology. Viruses with a frameshift mutation near the 5' end or with deletions in the central part of the coat protein gene failed to accumulate at detectable levels, even in the inoculated leaf. In protoplasts, mutants that infected systemically either had a wild-type phenotype or showed a small reduction in accumulation of genomic RNA. The other mutants, which did not accumulate in the inoculated leaf, were unaffected in genomic RNA accumulation 8 hr postinoculation, but at 16 hr and later they accumulated less genomic RNA than wild-type virus. None of the mutations had an effect on accumulation of negative-strand RNA. The data indicate that efficient accumulation and spread of PVX, even in the inoculated leaf, requires coat protein production and encapsidation of the viral RNA. PMID- 1413506 TI - Evidence for multiple species of vaccinia virus-encoded palmitylated proteins. AB - When cells were infected with vaccinia virus in the presence of [3H]palmitic acid, radiolabel was incorporated into six viral proteins with apparent molecular weights of 92, 41, 37, 26, 17, and 14 kDa, all of which are expressed at late times during the infection cycle. The [3H]palmitate-labeled fatty acid moieties from the modified proteins were isolated, converted to p-nitrophenacyl derivatives, and subjected to reverse phase HPLC analysis which confirmed the identity of the fatty acid group as palmitic acid. Furthermore, the radiolabeled palmitate-protein bonds were sensitive to treatment with neutral hydroxylamine, suggesting that association of the fatty acid moieties with these proteins occurs via a thioester linkage. Previous studies by other investigators have identified the 37-kDa protein as the major antigen present in the outer membrane of extracellular enveloped virions, and demonstrated that the protein is modified by palmitic acid but is not glycosylated (G. Hiller and K. Weber J. Virol. (1985) 55, 651-659). Growth of vaccinia virus in the presence of tunicamycin indicated that the 41- and 26-kDa palmitylated proteins were also subject to modification by glycosylation, whereas like the 37-kDa protein, the 92-, 17-, and 14-kDa species did not appear to be glycosylated. Subcellular fractionation studies provided evidence that all of the viral palmitylated proteins were membrane associated. Extraction of purified vaccinia virus with NP-40 and DTT demonstrated that the palmitylated proteins were associated with one of the viral membranes rather than the core of the virion. Viewing these results together with the previous reports of myristylated VV proteins (Franke et al. J. Virol. (1989) 63, 4285-4291), suggests that acylation of VV proteins represents a major modification pathway utilized by VV proteins during the assembly of progeny virions. PMID- 1413507 TI - Phylogenetic analysis of alphaviruses in the Venezuelan equine encephalitis complex and identification of the source of epizootic viruses. AB - We studied the evolution of alphaviruses in the Venezuelan equine encephalitis (VEE) complex using phylogenetic analysis of RNA nucleotide sequences from limited portions of the nsP4, E1, and 3' untranslated genome regions of representative strains. The VEE complex constituted a monophyletic group of viruses (descended from a common ancestor); some serologic VEE varieties such as subtype III formed monophyletic groups while subtype I did not. Subtype II Everglades and variety ID enzootic viruses formed a monophyletic group which also included all epizootic variety IAB and IC VEE isolates. Everglades virus diverged from this ID lineage (colonized North America) ca. 100-150 years ago, followed by divergence of variety IAB and IC epizootic viruses. Variety IAB viruses probably emerged from the variety ID lineage once during the early part of this century, while variety IC viruses evolved at least two times. These results identify the source of epizootic VEE viruses as the variety ID enzootic virus lineage which occurs in northern South America and Panama. Even if variety IAB and IC viruses are extinct, recent, multiple emergences of epizootic viruses from an enzootic lineage suggests that other epizootic VEE viruses may evolve again in the future. The close genetic relationship of subtype II Everglades virus to the variety ID lineage also implies the potential for emergence of equine-virulent VEE viruses in Florida. PMID- 1413508 TI - Characterization of the hepatitis B virus X- and nucleocapsid gene transcriptional regulatory elements. AB - The regulatory DNA sequence elements that control the expression of the hepatitis B virus X- and nucleocapsid genes in the differentiated human hepatoma cell lines, Huh7, Hep3B, PLC/PRF/5, and HepG2, the dedifferentiated human hepatoma cell line, HepG2.1, and the human cervical carcinoma cell line, HeLa S3, were analyzed using transient transfection assays. In this system, the hepatitis B virus enhancer I located between coordinates 1071 (-239) and 1238 (-72) increases transcription from the X-gene promoter located between coordinates 1239 (-71) and 1376 (+67) more than 30-fold in the differentiated hepatoma and the HeLa S3 cell lines. In the dedifferentiated hepatoma cell line, HepG2.1, the enhancer I sequence increases the level of transcription from the X-gene promoter approximately 10-fold. The enhancer I subregion between coordinates 1117 (-193) and 1204 (-106) appears to be important for enhancer function only in the differentiated hepatoma cell lines, whereas the enhancer I subregion between coordinates 1222 (-88) and 1238 (-72) is required for enhancer activity in each of the cell lines examined. In all of the cell lines, the X-gene minimal promoter element was within a 138-nucleotide sequence located between coordinates 1239 ( 71) and 1376 (+67). The enhancer I sequence increases transcription from the nucleocapsid promoter approximately 3- to 10-fold in the Huh7, Hep3B, PLC/PRF/5, and HeLa S3 cell lines, whereas it had little influence on the level of transcription from this promoter in HepG2 and HepG2.1 cells. The minimal nucleocapsid promoter element was within a 105 nucleotide sequence located between coordinates 1700 (-85) and 1804 (+20). This indicates that the levels of transcription from the X- and nucleocapsid gene promoters are determined in a cell-type-specific manner, in part, by the hepatitis B virus enhancer I and the corresponding minimal promoter sequence. PMID- 1413509 TI - Hepatitis B virus-DNA transfected myeloma cell-specific cytotoxic T cells in chronic hepatitis B patients. AB - To study the mechanisms of hepatitis B virus (HBV)-induced chronic hepatitis (B CH), we took chronic hepatitis B patients' peripheral blood lymphocytes (PBL) and examined their cytotoxic activities against human myeloma cells (ARH77) transfected by HBV-DNA. Two different transfected cells, one expressing HBV envelope antigens (S6) and the other expressing HBV core antigens (C4), were prepared and used as targets in the in vitro cytotoxic test. We found that PBL of B-CH patients had specific cytotoxic activity against these target cells (S6, 22.0 +/- 4.8%; C4, 21.6 +/- 4.8%), whereas no remarkable cytotoxic activity was observed in non-B chronic hepatitis patients as well as asymptomatic chronic HBV carriers. These specific cytotoxic activities were inhibited with anti-CD3 antibody, hence these killer cells belonged to T cells (cytotoxic T cells; CTL). The requirement of HLA class 1 antigens to exert these CTL activities was demonstrated by the absence of CTL activity with PBL obtained from HLA nonidentical B-CH patients and by the inhibition of their activities with anti HLA class 1 antibody. Thus, our results indicate that, at least two different CTL, one recognizing envelop antigen and the other recognizing core antigen, exist in chronic hepatitis B patients. PMID- 1413510 TI - Membrane fusion of mumps virus with ghost erythrocytes and CV-1 cells. AB - The octadecyl rhodamine (R18) fluorescent dequenching assay was used to examine membrane fusion between mumps virus and mammalian cells. Rapid fluorescent dequenching, indicative of membrane fusion, was observed when labeled mumps virus was mixed with either ghost erythrocytes or CV-1 cells. After 15 min a saturation limit of 18 virus per erythrocyte ghost and 6400 virus per CV-1 cell was observed. Fetuin was found to inhibit virus fusion, suggesting a role for sialic acid in virus binding to the cells. Two dequenching processes were observed of which the faster process is thought to be membrane fusion and the second process is thought to be probe proximal transfer. PMID- 1413511 TI - Mutational analysis of the monopartite geminivirus beet curly top virus. AB - Mutants of the monopartite geminivirus beet curly top virus have been screened for infectivity and symptom development in Nicotiana benthamiana and Beta vulgaris, for replication competence in N. benthamiana leaf discs, and for transmission by the leafhopper Circulifer tenellus. Disruption of open reading frame (ORF) V2 by the introduction of a termination codon resulted in symptomless infection of N. benthamiana associated with low levels of virus and reduced single-stranded (ss) DNA and prevented systemic infection of B. vulgaris. Reduced levels of ssDNA were produced by the mutant in N. benthamiana leaf discs, suggesting that V2 affects the synthesis or accumulation of this viral DNA form. Mutants in which ORF C2 had been truncated by the introduction of termination codons or by frame-shifting remained highly infectious and induced severe symptoms in both N. benthamiana and B. vulgaris. Similarly, a mutant containing a termination codon within ORF C3 was highly infectious and induced severe symptoms in N. benthamiana although infectivity in B. vulgaris was greatly reduced, symptoms were extremely mild, and virus levels were low. A synergistic effect of a double mutation in ORFs C2 and C3, manifested by the inability of mutants to systemically infect N. benthamiana and the production of reduced amounts of ssDNA in N. benthamiana leaf discs, suggests that both ORFs are functional in this host. A mutant containing a termination codon within the 5' terminus of ORF C4 produced severe symptoms in both N. benthamiana and B. vulgaris resembling those induced by wild-type virus. Comparison with the phenotypes of previously characterized ORF C4 mutants suggests that a conserved core sequence of this ORF is an important symptom determinant. ORF C2, C3, and C4 mutants produced virus particles and were transmitted by C. tenellus, eliminating agroinoculation as a contributory factor to the mutant phenotypes. Our results are compared with those derived from mutagenesis studies on related bipartite geminiviruses. PMID- 1413512 TI - Expression of functional parvoviral NS1 from recombinant vaccinia virus: effects of mutations in the nucleotide-binding motif. AB - The gene encoding the major replicative protein, NS1, of minute virus of mice (MVM) was transferred into a recombinant vaccinia virus vector in place of the vaccinia thymidine kinase gene. The NS1 gene was placed under control of a bacteriophage T7 promoter and expressed in cells coinfected with another recombinant vaccinia virus, vTF7-3, which encodes the T7 RNA polymerase. Expression of NS1 was further enhanced by the presence of a 5' untranslated region, derived from encephalomyocarditis virus, which allows efficient cap independent translation. This system was used to produce and analyze wild-type NS1 and two mutant forms of the protein, NS1K405R and NS1K405M, in which the highly conserved lysine codon located in the putative purine triphosphate binding site of NS1 was changed to arginine and methionine, respectively. Full-length NS1 was expressed efficiently in both human and mouse cells infected with each of the three recombinant viruses, and in each case the NS1 was rapidly and efficiently translocated into the nucleus. Wild-type NS1 expressed in this way was biologically active. It was able to trans-activate an MVM P38 promoter located in a host chromosomal site, whereas the two mutant forms of NS1 showed no significant activity in this assay, and it was capable of resolving palindromic junction fragments cloned from multimeric MVM replicative form DNA molecules. These substrates, representing MVM genomic left-end:left-end and right-end:right end fusions, were resolved in a DNA synthesis-dependent in vitro reaction supplemented with nuclear extracts containing recombinant wild-type NS1. Neither of the two mutant forms of the polypeptide had any detectable activity in this assay. PMID- 1413513 TI - Polylactosaminoglycan modification of the respiratory syncytial virus small hydrophobic (SH) protein: a conserved feature among human and bovine respiratory syncytial viruses. AB - We investigated the nature of the oligosaccharide modification of the glycosylated forms of the small hydrophobic integral membrane protein, SH (previously designated 1A), of respiratory syncytial (RS) virus. Analysis of SH protein expressed in cells infected with RS virus or with a recombinant vaccinia virus revealed two glycosylated SH protein species, SHg and SHp, which contained N-linked carbohydrate residues. SHp migrated diffusely on polyacrylamide gels, which suggested modification by polylactosaminoglycan oligosaccharides. Polylactosaminoglycan modification of SHp was established from three lines of investigation: (1) the synthesis of SHp in a cell line (IdID) conditionally defective in the ability to add specific carbohydrate residues to N- or O-linked oligosaccharide chains required the addition of galactose, which is a component of the N-acetyllactosamine repeating unit; (2) SHp was sensitive to digestion with endo-beta-galactosidase, which cleaves the beta 1-4 linkage between galactose and N-acetylglucosamine of the repeated N-acetyllactosamine subunit; and (3) SHp was selected by Datura stramonium lectin (Dsl), which has specificity for polylactosaminoglycans. The presence of SHp as a component of purified human subgroups A and B and bovine RS virus particles was demonstrated by Dsl affinity selection. In addition to SHp, nonglycosylated SHo was selected by Dsl affinity, indicating that SHp and SHo may associate to form complexes within infected cells and virus particles. To identify conserved amino acid residues among the human and bovine SH glycoproteins that may function as signals for polylactosaminoglycan modification, the nucleotide sequences of the SH protein genes of a human subgroup B virus (8/60) and a bovine virus (391-2) were determined and compared to those of a human subgroup A virus (A2), a subgroup B virus (18537), and a bovine virus (A51908). A comparison of the deduced amino acid sequences of the human and bovine RS virus SH proteins indicated that a central hydrophobic region and the presence of potential N-linked glycosylation sites on either side of the central hydrophobic region were conserved features that may be required for the polylactosaminoglycan modification of SH. PMID- 1413514 TI - Hyperexpression of baculovirus polyhedrin and p10 is inversely correlated with actin synthesis. AB - Polyhedrin and p10, two proteins encoded by Autographa californica M nuclear polyhedrosis virus, are hyperexpressed very late during normal infections. In this study we found that cytochalasin D, a drug that leads to increased actin synthesis in infected and uninfected host cells, delayed the amplified expression of polyhedrin and p10 when added to infected cells before hyperexpression was already in progress. Restoration of polyhedrin and p10 hyperexpression could be achieved by removal of the drug, but required new protein synthesis. An inverse correlation was observed between polyhedrin/p10 mRNA levels and actin mRNA levels at late and very late times during infection, regardless of whether cytochalasin D was added, removed, or never present. In comparison to mRNAs of polyhedrin and p10, the mRNA levels of the early/late viral gene 39K were much less affected by cytochalasin D and responded to drug removal more slowly. The results of these studies revealed an apparent correlation between the shut down of host actin genes and the amplified expression of polyhedrin and p10 in the presence and absence of cytochalasin D. The possibility that newly synthesized actin itself, either directly or indirectly, plays a negative regulatory role in the accumulation of polyhedrin and p10 mRNAs is discussed. PMID- 1413515 TI - Analysis of 3' and 5' ends of N and NSs messenger RNAs of Toscana Phlebovirus. AB - The 5' and 3' ends of N and NSs mRNAs, transcribed from the S segment of Toscana Phlebovirus, were analyzed by oligonucleotide primer extension and S1 nuclease mapping procedures. The results showed that both mRNAs acquired, at their 5' end, approximately 9-15 nucleotides not present in the viral template, suggesting an initiation transcription mechanism similar to the one described for influenza virus. Furthermore, the 3' ends of the two mRNAs were located in a sequence motif conserved in the S segment of two other Phleboviruses, the Rift Valley Fever and Sandfly Fever Sicilian viruses. This finding suggests the possible involvement of this sequence in the mechanism of transcription termination. PMID- 1413516 TI - Characterization of the antibody response to three different versions of the HTLV I envelope protein expressed by recombinant vaccinia viruses: induction of neutralizing antibody. AB - Recombinant vaccinia viruses (RVV) designated RVV E1, RVV E2, and RVV E3, were constructed to express three different versions of the human T cell leukemia virus type I (HTLV-I) envelope proteins to determine which configuration elicits an optimal antibody response. RVV E1 expressed the native HTLV-I envelope proteins gp46 (surface protein) and gp21 (transmembrane protein), while RVV E2 expressed the envelope precursor with the proteolytic cleavage site deleted. The RVV E3 construct expressed only the external surface glycoprotein, gp46. Radioimmunoprecipitation and FACS analysis confirmed that the appropriate envelope proteins were expressed by RVV E1-, E2-, and E3-infected cells. Immunization studies were carried out using Balb/c, A/J, and C57BL/6 strains of mice. Balb/c mice responded poorly to immunization with all of the three RVV constructs. C57BL/6 mice produced neutralizing antibodies in response to immunization with all three constructs, whereas A/J mice developed neutralizing antibodies only when immunized with the RVV E1s construct. The results indicate that the humoral immune responses depend on the form of HTLV-I envelope proteins expressed by each RVV. PMID- 1413517 TI - cis-acting elements for in trans complementation of replication-defective mutant of tobacco mosaic virus. AB - We have shown that virus-encoded replicase components of tobacco mosaic virus (TMV)(130K/180K proteins) could complement a replication-defective mutant (LDR28) for viral replication in trans [Ogawa et al. Virology 185, 580-584 (1991)]. Using this trans-complementation system, we investigated the dispensability of regions of the 130K/180K protein genes as cis-acting elements for viral replication. A series of replication-defective mutants (LDRs) which had various deletions in the 130K/180K coding region were constructed. These were co-inoculated with a replication-competent mutant (LDCS29) into tobacco protoplasts. Accumulation of LDR-genomic RNA, CP mRNA, and CP was much increased by the removal of the 3' terminal one-third of the readthrough part of 180K protein gene (residues 4529 4937 of TMV-RNA) from LDR, suggesting that this region interferes with the viral replication in this trans-complementation system. In addition, accumulation of CP mRNA and CP was much decreased by the removal of the 5'terminal half of the 30K protein gene (residues 4938-5263 of TMV-RNA), suggesting the presence of an element to enhance the synthesis of CP mRNA in this region. PMID- 1413518 TI - Structural and functional organization of the human endogenous retroviral ERV9 sequences. AB - The human genome contains a variety of genetic elements similar in structure to retroviruses and retrotransposons. We report here the structural and functional organization of a novel human endogenous retroviral family (ERV9). Three polyadenylated RNAs, 8, 2, and 1.5 kb long, are detected by Northern blot in undifferentiated embryonal carcinoma NT2/D1 cells. Upon genomic cloning of an expressed ERV9 locus, we demonstrated that the three polyadenylated RNAs are originated by a single ERV9 locus by alternative usage of splicing and polyadenylation signals. DNA sequence analysis of different ERV9 LTRs have revealed that they are heterogeneous in length and that the length variability is due to the number of tandemly repeated subelements present in both U3 and U5 regions; moreover, the ERV9 LTRs are capable to drive expression of a reporter gene in transient expression assays. Finally, analysis of the ERV9 5' transcription start site has allowed us to define the U3-R-U5 organization of the ERV9 LTR. PMID- 1413519 TI - Nucleotide sequence identifies Vilyuisk virus as a divergent Theiler's virus. AB - The Vilyuisk virus, originally thought to be the cause of a degenerative neurological disease of inhabitants of Siberia, has been characterized by sequence analysis of its 5' noncoding and coat protein coding regions. In the 5' noncoding, leader, and VP4 regions, the nucleotide identity between the sequences of known strains of Theiler's virus and Vilyuisk virus is about 90%. In the VP1 encoding region, the similarity drops to about 66% compared to the 50% similarity between sequences of Theiler's virus and encephalomyocarditis virus. Using the known crystal structure of one Theiler's virus strain, it is shown that the sequence heterogeneities generally occur at exposed surface residues. Vilyuisk virus is the most divergent Theiler's virus known. A tissue culture-adapted isolate has been propagated and found to exhibit low neurovirulence in CD-1 mice. PMID- 1413520 TI - The coat protein of white clover mosaic potexvirus has a role in facilitating cell-to-cell transport in plants. AB - Functions of the coat protein of white clover mosaic potexvirus (WCIMV) were investigated using C-terminal deletion mutants. Whereas plants inoculated with RNA transcripts of a full-length wild-type clone of WCIMV produced typical infections, plants inoculated with transcripts of each mutant did not produce symptoms, and viral RNA species were not detected by Northern analysis. The mutants were able to replicate in protoplasts, although, relative to the wild type RNA profile, the level of genomic RNA, but not subgenomic RNA, was reduced. These results indicate a role for the coat protein in efficient cell-to-cell transport in plants. Virus-like particles were detected in protoplast extracts inoculated with transcripts of a mutant in which the coat protein was truncated by 31 amino acids. This result suggests that the lack of detectable transport in plants was not due solely to a failure of the mutants to form virus particles. Possible roles for the coat protein in transport and replication are discussed. A 6-kDa open reading frame, internal to the coat protein gene, was shown by mutational analysis not to be essential for replication or transport. PMID- 1413521 TI - The genome of bovine ephemeral fever rhabdovirus contains two related glycoprotein genes. AB - A 3789 nucleotide region of the bovine ephemeral fever virus (BEFV) genome, located 1.65 kb downstream of the N gene, has been cloned and sequenced. The region contains two long open reading frames (ORFs) which are bounded by putative consensus (AACAGG) and polyadenylation (CATG[A]7) sequences and are separated by an intergenic region of 53 nucleotides. Discrete mRNAs corresponding to each ORF have been identified. The first ORF encodes a polypeptide comprising 623 residues which was identified by peptide sequencing as the virion G protein. The deduced amino acid sequence of the G protein includes putative signal and transmembrane domains and five potential glycosylation sites. The second ORF encodes a polypeptide of 586 amino acids which also has characteristics of a rhabdovirus glycoprotein, including putative signal and transmembrane domains and eight potential glycosylation sites, and appears to correspond to a 90-kDa nonstructural glycoprotein (GNS) identified in BEFV-infected cells (Walker et al. [1991] J. Gen. Virol. 72, 67-74). A database search indicated that both the G and GNS proteins share significant amino acid sequence homology with other rhabdovirus G proteins and with each other. Highest homology scores for each protein were with sigma virus and vesicular stomatitis virus serotypes. PMID- 1413522 TI - Functional organization of enhancer (ENII) of hepatitis B virus. AB - A new enhancer ENII, located in the X open reading frame and immediately upstream of the core gene promoter, has recently been identified in the genome of hepatitis B virus. We have studied the functional constituents of this new enhancer in different cell lines. ENII can be divided into two functional elements, A and B, corresponding to two major binding sequences for nuclear protein factors. Element A alone gave very low activity; however, it was a modulatory element important for cell-type specificity. Element B was shown to be the basic functional element of ENII, which retained about 70% of the enhancer activity of the complete ENII in HepG2 cells. Element B can be further dissected into three subunits, B1, B2, and B3, which act synergistically. A 52-bp sequence is identified as the core sequences of element B. A model for the mechanism of ENII function is proposed. PMID- 1413523 TI - African swine fever virus-induced DNA polymerase is resistant to aphidicolin. AB - African swine fever virus (ASFV) induces the synthesis of a virus-specific DNA polymerase, which is inhibited by phosphonoacetic acid and cytosine arabinoside. In contrast to all other alpha-like DNA polymerases of DNA viruses, ASFV-specific DNA polymerase is resistant to aphidicolin. Concentrations of the drug as high as 160 microM had no effect on virus production or plaquing efficiency. The resistance of ASFV DNA polymerase to aphidicolin was confirmed by analyzing the effect of the drug on viral DNA synthesis. A moderate inhibition of viral DNA synthesis was observed when aphidicolin was added immediately after virus adsorption but normal synthesis occurred, with a peak at 10 hr p.i., when the drug was added at 2 or 4 hr p.i. This suggests that a very early phase of ASFV DNA replication is sensitive to aphidicolin and is probably catalyzed by a different enzyme. An in vitro assay of DNA polymerase activity was used to assay the sensitivity of the virus-specific DNA polymerase to inhibitors. In correspondence to the results observed in vivo, phosphonoacetic acid strongly inhibited the enzyme activity, whereas aphidicolin had no effect. Resistance to aphidicolin was independent of the concentration of dCTP used in the assay. Three independent ASFV mutants resistant to phosphonoacetic acid showed the same resistance to aphidicolin as wild type virus. PMID- 1413524 TI - Human coronavirus gene expression in the brains of multiple sclerosis patients. AB - Total RNA extracted from both white and gray matter of brain tissue from multiple sclerosis (MS) patients and controls was analyzed using a reverse transcription polymerase chain reaction for the presence of the nucleic acid of human coronavirus (HCV) 229E and OC43, the two strains characterized to date and associated with respiratory infections. HCV-229E viral RNA was detectable in the central nervous system tissue of 4 of 11 MS patients and in none of 6 neurological and 5 normal controls. No HCV-OC43 nucleic acid was detected in any of the specimens. These results suggest a neurotropism on the part of the 229E strain of human coronavirus and underline the importance of further studies on its tissue distribution. The fact that it was detected only in tissue from MS patients illustrates the need for continued studies on the possible role of coronaviruses in the etiology of MS. PMID- 1413525 TI - Nucleotide sequence changes in the polymerase basic protein 2 gene of temperature sensitive mutants of influenza A virus. AB - Influenza A viruses bearing temperature-sensitive (ts) mutations are restricted in replication in the respiratory tract of animals and humans and are therefore attenuated. Nucleotide sequences were determined for the RNA segment coding for the polymerase basic protein 2 (PB2) from a panel of 12 influenza A/Udorn/307/72 (H3N2) ts viruses, previously characterized to have a ts mutation in the PB2 gene. Each of the viruses with a ts mutation in the PB2 gene had a single amino acid change located at position 65, 100, 112, 174, 298, 310, 386, 391, 556, or 658 of the PB2 protein. The sites of the single mutations were scattered throughout the length of the protein and occurred in regions that are highly conserved among the influenza A virus PB2 predicted amino acid sequences. Interestingly, the substitution of aspartic acid for asparagine at position 556 was found to lie within a region that has homology with cap-binding motifs of human and yeast proteins. Taken together, the findings of lesion sites in the A/Udorn/307/72 PB2 gene and the three reported amino acid changes at positions 265, 417, and 512 for A/AA/6/60, A/WSN/33, and A/FPV/Ros/34 ts PB2 genes, respectively, indicate that the PB2 gene can sustain a viable ts mutation at different sites. This information will allow us to construct cloned cDNA copies of the A/Udorn/307/72 PB2 gene mutagenized at specific sites. Different configurations of two or more ts mutations may be incorporated into the cDNA PB2 gene constructs. We have a host-range reassortant virus that should permit rescue of in vitro-produced transcripts of the PB2 gene into infectious virus. The rescue of these mutated PB2 RNA segments into an infectious influenza A virus may lead to the development of live attenuated reassortant virus vaccines that are satisfactorily attenuated, genetically stable, and immunogenic in humans. PMID- 1413527 TI - Molecular characterization of a polymerase mutant human immunodeficiency virus. PMID- 1413526 TI - Cell receptor-independent infection by a neurotropic murine coronavirus. AB - The cellular receptors for a coronavirus, mouse hepatitis virus (MHV), have been recently identified as one or more members of the carcinoembryonic antigen (CEA) family. The neurotropic JHM strain of MHV (MHV-JHM) possesses a highly fusogenic surface (S) glycoprotein. This protein is now shown to promote the spread of MHV into cells lacking the specific CEA-related MHV receptor. Resistant cells are recruited into MHV-induced syncytium with consequent production of progeny virus. Cell-to-cell spread of virus via membrane fusion without the requirement for specific cell surface receptor offers a novel way for virus to spread within infected hosts. PMID- 1413528 TI - A regulatory role for the 32K protein in proteolytic processing of cowpea mosaic virus polyproteins. AB - We have studied the regulation of proteolytic processing of the polyproteins encoded by cowpea mosaic virus M-RNA and B-RNA. For that purpose mutations were introduced in full-length cDNA clones of these RNAs. RNA transcripts were translated in rabbit reticulocyte lysate and the effect of mutations on the processing was analysed. These studies revealed that the 32K protein is released from the 200K B-polyprotein by an intramolecular cleavage and remains associated with the 170K protein, probably by interaction with the 58K domain of the 170K protein. In this complex the conformation of the 170K protein is such that further cleavages are very slow. This complex carries out the processing of the Gln/Met site in the M-polyprotein. The 170K protein produced by a B-RNA mutant that lacks the 32K coding region was efficiently processed into 110K, 87K, 84K, 60K, 58K and 24K cleavage products. Thus, the 32K protein regulates the B polyprotein processing by slowing it down and, on the other hand, enhances trans cleavage of M-polyproteins at a Gln/Met site. PMID- 1413529 TI - Processing of VPg-containing polyproteins encoded by the B-RNA from cowpea mosaic virus. AB - To study the processing of putative VPg precursors the expression of specific mutant transcripts derived from a full-length cDNA clone of cowpea mosaic virus (CPMV) B-RNA was examined in a rabbit reticulocyte lysate system. This study revealed that the 170K protein produced by a B-RNA mutant that lacks the 32K coding region was efficiently processed by mainly intramolecular cleavages at three different sites into three sets of proteins of 60K + 110K, 84K + 87K, and 58K + 112K. Further cleavage of the 60K protein into 58K and VPg has not been observed in this in vitro system. The 84K protein can be further processed by an intramolecular cleavage reaction via two alternative pathways, either into 26K (VPg + 24K) and 58K proteins or into 24K and 60K proteins. VPg can be released from the 112K (VPg + 110K) precursor either directly or via the 26K intermediate. Immunoblot analysis showed that the 112K protein is present in CPMV-infected plant cells indicating that the in vitro observations may hold true in vivo. PMID- 1413531 TI - [Transformation by the tax gene of HTLV-1]. PMID- 1413530 TI - The nucleotide sequence of apple stem grooving capillovirus genome. AB - The complete nucleotide sequence of apple stem grooving virus (ASGV) genome has been determined. The genome is 6496 nucleotides in length excluding a 3'-terminal poly(A) tail and contains two overlapping open reading frames (ORFs). ORF1 begins at nucleotide position 37 and is terminated at position 6341, encoding a protein with a molecular weight of 241 kDa. ORF2, which is in a different reading frame within ORF1, begins at position 4788 and can encode a 36-kDa protein. The 241-kDa protein contains two consensus sequences associated with the RNA-dependent RNA polymerase and the NTP-binding helicase. Comparisons of amino acid sequences around these conserved motifs with other RNA viruses revealed that ASGV has extensive similarities with apple chlorotic leaf spot, tymo-, carla-, and potexviruses, and is a member of the sindbis-like supergroup. ASGV coat protein is found to be located in the C-terminal region of the 241-kDa polyprotein. The 36-kDa protein encoded by ORF2 contains the consensus sequence Gly-Asp-Ser-Gly found in the active site of several cellular and viral serine proteases. PMID- 1413532 TI - [The clinical features of HTLV-I infection. HTLV-I associated myelopathy]. PMID- 1413533 TI - [Immune response to HTLV-I infection]. PMID- 1413534 TI - [Regulatory mechanism of HTLV-1 replication and its association with abnormal cell growth]. PMID- 1413535 TI - [Transmission of HTLV-I]. PMID- 1413536 TI - [Epidemiology of HTLV-I]. PMID- 1413537 TI - [Genetic engineering of negative strand RNA viruses]. PMID- 1413538 TI - [A brief chronological history of some critical publications on the discovery of retrovirus etiology of adult T-cell leukemia (ATL)]. PMID- 1413539 TI - The 3'-nucleotide sequence of an ordinary strain of potato virus S. AB - The sequence of 1346 nucleotides of the 3'-terminal region of an ordinary strain of potato virus S was determined from cloned cDNA. This portion of the viral RNA contains two major open reading frames (ORFs), encoding the coat protein of M(r)33K and a protein of M(r)11K 3' to the coat protein, both of which showed high homology, 93% and 79%, respectively, with the equivalent proteins of the Andean strain. A major block of amino acids that differ between the ordinary and Andean strains was present in both the coat protein and the 11K. These blocks may be responsible for the substantial differences between the ordinary and Andean strains at the symptom and aphid transmissibility levels. PMID- 1413540 TI - Expression of biologically active HIV glycoproteins using a T7 RNA polymerase based eucaryotic vector system. AB - Bacteriophage T7 RNA polymerase and a derivative containing a nuclear localization signal were transiently expressed in CV-1 cells and were shown to localize to the cytoplasm and nucleus, respectively. A vector was constructed containing T7 promoter and transcription terminator sequences flanking a picornaviral 5' untranslated sequence for cap-independent translation and a polyA signal. Expression of the HIV-1 envelope glycoproteins in this vector system gave high levels of specific transcripts and translation products, independent of the subcellular localization of T7 RNA polymerase. The synthesis of HIV glycoproteins was also completely independent of the coexpression of the HIV rev protein, which is normally required for the expression of HIV structural proteins. In addition, a polyA signal was not required, whereas the presence of the picornaviral 5' untranslated region was necessary for efficient expression. Different possibilities to account for these findings are discussed. The HIV glycoproteins synthesized in this system were normally processed and assembled; they could induce syncytium formation and complement an env-deletion mutant of HIV-1. PMID- 1413541 TI - Multiple cis-acting DNA elements that regulate transcription of the adenovirus 12 E1A gene. AB - To delineate cis-acting elements for adenovirus (Ad) 12 E1A gene transcription, we transfected HeLa and NIH3T3 cells with DNAs having various deletions in the 5' upstream region linked to the chloramphenicol acetyltransferase gene. Deletions in the regions between nucleotide (nt) positions 54 and 166, and 167 and 200, with respect to the left end of the viral genome at nt position 1, caused a two- to three-fold reduction in transcription. Transcription decreased to an almost undetectable level with loss of the region between nt positions 201 and 282. The effect of these mutations was almost consistent between both cell lines. The region between nt positions 77 and 94 stimulated transcription when situated upstream of the simian virus 40 early promoter in either orientation. Transcription was stimulated about ninefold in the presence of the DNA that encodes the product of the 13S, but not the 12S mRNA of the Ad12 E1A gene. These results indicate that transcription of the Ad12 E1A gene is regulated by multiple cis-acting elements and is stimulated by its own gene product. PMID- 1413542 TI - Neutralizing monoclonal antibodies against alpha and beta subunits of the Ustilago maydis virus encoded toxin. AB - The toxins secreted by Ustilago maydis are encoded by dsRNA viruses. The KP6 toxin encoded by subtype P6 consists of two polypeptides alpha and beta, which are not covalently bound. Neutralizing monoclonal antibodies (MoAbs) were raised against each subunit. Some of the anti-beta MoAbs identify different epitopes in the antigen. The MoAbs were used to affinity purify alpha and beta polypeptides from culture media and to detect the precursor of the mature toxin. PMID- 1413543 TI - Nucleotide and deduced amino acid sequence of the canine adenovirus type 1 proteinase. AB - The DNA sequence of an open reading frame (ORF) corresponding to the canine adenovirus type 1 (Can1) proteinase gene was determined. A total of 1171 base pairs were sequenced from the downstream end of the HindIII-A Can1 genomic fragment, including adjacent regions corresponding to the carboxy-terminal portions of the hexon and the DNA-binding proteins. The predicted Can1 proteinase consists of 206 residues (23,325 D) of which 68% are identical and 83% are similar to the sequence of the human Ad2 proteinase. Alignment with the Ad2 proteinase identified a number of conserved residues that could form part of the catalytic triad of the enzyme. PMID- 1413544 TI - The phase of PVEP in Maxwellian view: influence of contrast, spatial and temporal frequency. AB - The temporal phase of the pattern reversal VEP has been investigated using stimulation with laser interference fringes in Maxwellian view. VEP phase was almost constant as function of spatial frequency (2-30 c/deg, 6.5 r/sec, 51 subjects). The phase function however shows a small phase increase at low spatial frequencies consistent with the existence of multiple temporal mechanisms. Contrast variation yields a smaller phase increase with decreasing contrast than conventional stimulation. The phase is linear as function of reversal rate (2-31 r/sec) for low and high spatial frequencies. The indication of more than one temporal mechanism has also been found when the test field diameter was varied. With decreasing test field size the phase increases at 6.5 r/sec, but decreases at 18 r/sec (for 12 c/deg). PMID- 1413545 TI - Pharmacological study of the chicken's monocular optokinetic nystagmus: involvement of the ON retinal channel evidenced by the glutamatergic separation of ON and OFF pathways. AB - The chicken's monocular optokinetic nystagmus (OKN), recorded by the magnetic search coil technique, displays a directional asymmetry, the temporal-nasal (T-N) stimulation being more efficient than the nasal-temporal (N-T) one to evoke the reflex. The intravitreal administration of APB, a glutamate agonist which selectively blocks the ON retinal channel strongly reduced the eye monocular OKN; it also induced spontaneous eye movements in the T-N direction. The intravitreal injection of PDA another glutamate analog, which reduces the OFF channel, while increasing the activity of the ON channel, induced a large increase in OKN velocity gain, especially for a N-T stimulation at the lowest drum speeds. These results indicate the main involvement of the ON retinal channel in the OKN genesis and the inhibitory effect of the OFF channel upon this oculomotor reflex. PMID- 1413546 TI - The development of maximum displacement limits for discrimination of motion direction in infancy. AB - The development of visual motion mechanisms has been studied in infants by using forced-choice preferential looking to measure maximum displacement limits (dmax) for the detection of coherent motion in random-dot patterns. The motion consisted of a sequence of coherent displacements at intervals of 20 msec. Between 8 and 15 weeks, dmax for discrimination of coherent from incoherent motion, and for discrimination of opposite directions of coherent motion, increased with age; in both conditions, dmax for the oldest infants was less than a third of the value found in adults. For 10-11-week-old infants, and for an adult subject, reducing stimulus contrast from 88 to 48% had no effect on dmax for direction discrimination, which indicates that the rise in dmax with age is not simply a result of improving contrast sensitivity. When the displacement interval was increased from 20 to 40 msec, dmax increased significantly in 8-11-week-olds, but remained unchanged in 12-15-week-olds. These results show that while directional mechanisms are present in the visual system by 8 weeks, they operate over a restricted velocity range. The upper limit of this velocity range increases with age. After about 12 weeks, the increase is mainly due to changes in the spatial properties of motion mechanisms; however, in younger infants changes in their temporal properties are also important. PMID- 1413547 TI - Contrast sensitivity as a function of spatial frequency, viewing distance and eccentricity with and without spatial noise. AB - Using computer graphics and a two-alternative forced-choice method we measured threshold contrast as a function of viewing distance, spatial frequency, and eccentricity for gratings with and without added, white two-dimensional spatial noise. Our experiments showed that in spatial noise contrast sensitivity was independent of viewing distance as long as contrast sensitivity was lower with noise than without. With increasing spatial frequency (f) the grating area (A) was reduced in order to keep the relative grating size (Af2) constant. At all spatial frequencies the test gratings thus had the same amount of detail and contour. Noise spectral density was reduced in direct proportion to grating area in order to keep the physical signal-to-noise ratio constant. An increase in spatial frequency was thus accompanied with reductions in grating area and noise spectral density similar to those produced by a corresponding increase in viewing distance. In agreement, contrast detection in spatial noise was found to be independent of spatial frequency as long as contrast sensitivity was lower with noise than without. The effect of increasing eccentricity on visual performance can be compensated for by reducing the viewing distance (M-scaling). Hence, without M-scaling the effect of increasing eccentricity is similar to that of increasing viewing distance. In agreement, we found that contrast sensitivity in spatial noise was independent of eccentricity as long as contrast sensitivity was lower with noise than without. PMID- 1413548 TI - Effects of contrast substitutions upon motion detection in spatially random patterns. AB - We report the effects of contrast changes between frames in a random-square kinematogram. When the contrasts of both frames are too low to permit directional discrimination, increasing the contrast of either the first or the second frame alone makes directional discrimination possible. However, at suprathreshold contrasts for motion detection, increasing the contrast of either the first or the second frame alone makes discrimination more difficult. We conclude that motion detection is a special case of contrast discrimination, in agreement with the Reichardt model of motion detection. PMID- 1413549 TI - Scotopic visual efficiency: constraints by optics, receptor properties, and rod pooling. AB - We studied the influence of optics, photoreceptor properties, and rod pooling on scotopic contrast sensitivity by comparing the performance of an ideal discriminator to that of human observers. Comparisons of human and ideal contrast sensitivities indicated that preretinal factors and summation area were not sufficient to explain the shape of the human CSF. Spatial pooling of rods was explored as a possible explanation of this discrepancy. Our highest efficiency, expressed in terms of a human/ideal contrast sensitivity ratio, was about 1:3 (0.33) for a contrast discrimination task. PMID- 1413550 TI - The role of color in the motion system. AB - We have examined the ability of observers to determine the direction of movement of a variety of colored plaid patterns. When the two plaid components are of unequal spatial frequency or of unequal luminance or chromatic contrast, observers judge the direction of movement incorrectly. These errors are correlated with a misjudgement of the speeds of the two components. Our results provide support for an initial decomposition into oriented components followed by a subsequent component-to-pattern recombination of moving equiluminant and colored plaids. At equal multiples of threshold contrast a moving luminance grating is about 8 times more powerful than a moving equiluminant grating in determining the apparent direction of motion of a plaid. When both are present, luminance and color do not interact linearly. Color and motion must be processed in parallel in at least partially separate pathways. PMID- 1413551 TI - Head-centric visual localization with lateral body tilt. AB - The aim of the present investigation was to decide whether subjects can correctly judge the head-centric orientation of a display in the dark in spite of the counterrolling of their eyes caused by head tilt. Four subjects were asked to set two luminous points orthogonally to the median plane of their heads, with head and body upright or tilted 90 degrees to the left or right side. The luminous points could be rotated in a frontal plane about a stationary fixation light situated straight ahead. Subjects viewed this display monocularly with either eye. In the same three body positions, ocular counterroll was determined photographically. The settings turned out to be neither accurately oculocentric nor head-centric, and there were considerable inter- and intrapersonal variances. However, on average, display adjustments were more head-centric: mean difference of ocular counterroll between left-ear-down and right-ear-down conditions was 13.2 deg, whereas the mean difference of the subjective head-centric orientations was only 3.8 deg. PMID- 1413552 TI - Predictive smooth pursuit eye movements near abrupt changes in motion direction. AB - The stimulus-response characteristics of predictive smooth pursuit eye movements near the time of predictable, abrupt changes in target motion direction were studied. Expectations about the speed and direction of target motion both before and after the direction change affected specific components of the predictive pursuit responses. We propose that, when the direction of target motion is expected to change, the cessation of motion in one direction and the initiation of motion in a new direction are separately anticipated and that predictive pursuit movements are summated responses to these two events. PMID- 1413553 TI - Two-stage analysis of the motion of 2-dimensional patterns, what is the first stage? AB - The sum of two differently orientated moving sinusoidal gratings of similar spatial frequency, contrast, and velocity appears as a single coherent "plaid" pattern. The visual system is thought to analyse the motion of plaids in two stages, first analysing the motion of the (1-D) components, and then calculating a speed and direction which is consistent with those 1-D motions. We find that the direction of motion of a plaid (components 1.6 c/deg orientated +60 degrees and -60 degrees) can be discriminated at velocities so low that the direction of motion of its components is not discriminable. This finding is not consistent with the "two-stage" hypothesis in the form that it is usually expressed. We suggest that mechanisms sensitive to the motion of local elements in the pattern, such as edges, could also contribute to the first stage of the analysis of plaid motion. PMID- 1413554 TI - Analysis of the motion of 2-dimensional patterns: evidence for a second-order process. AB - The sum of two differently orientated moving sinusoidal gratings of similar spatial frequency, contrast, and velocity appears as a single coherent "plaid" pattern. The visual system is thought to analyse the motion of plaids in two stages, first analysing the motion of the (1-D) components, and then calculating a speed and direction which is consistent with those 1-D motions. We studied the apparent direction of motion of plaids made by adding two components that had the same spatial frequency and contrast, and were symmetrically oriented about the vertical axis. The gratings moved in jumps, and we studied the effect of varying the size of the jump, the angle between the component gratings, and the temporal interval between the jumps, on the perceived direction of motion. When the size of the jumps was increased to 3/8 of their spatial period, the perceived direction of motion of the plaid pattern reversed, although if one component were presented alone, its direction of movement did not reverse. Reversed motion of this type was consistently obtained if the angle between the components was greater than about 140 degrees, if the interval between jumps was at least 25 msec, and if the spatial frequency of the component gratings was less than about 4 c/deg. When the angle between the components was smaller, or the time between jumps was greater, most observers saw normal motion in the direction predicted by the two-stage hypothesis. When the spatial frequency was raised, observers saw no consistent motion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413555 TI - A comparison between colour and luminance contrast in a spatial linking task. AB - We report experiments which compare the ability of subjects to employ colour vs luminance contrast as a basis for discriminating the degree of collinearity of random element string pairs. The purpose of the study was to determine the extent to which spatial integration mechanisms could utilize colour contrast. In order to probe directly the processes of spatial integration per se, it was necessary to control for any differences in the efficiency with which the visual system utilized colour and luminance contrast to locate the positions of the individual elements in the test stimuli. To do this we first established the "equivalent" luminance contrast of an isochromatic stimulus which produced equal performance to an isoluminant stimulus in a 2 element per string alignment task. This equated the colour defined and luminance defined stimuli for local positional acuity. We then measured performance for both isoluminant and equivalent luminance contrast stimuli for strings consisting of 2, 4, 8 and 16 elements. This tested for any differences in the processes of spatial integration. For both unmasked stimuli and stimuli embedded in luminance noise, there was no consistent trend favouring either luminance or colour contrast as the number of elements in the stimuli was increased. We conclude that the visual system is able to employ colour contrast as efficiently as luminance contrast for collinearity judgements, thus implicating a general role for colour vision in spatial integration tasks. PMID- 1413556 TI - Nonlinear processes in spatial-frequency channel models of perceived texture segregation: effects of sign and amount of contrast. AB - Observers rated the degree of segregation between two textures, each composed of the same two element types but in differing arrangements (a checkerboard arrangement in the middle region of the pattern and a striped arrangement in the top and bottom regions). The two element types in a given pattern were either both solid squares or both center-surround elements. In center-surround elements the average luminance equaled the background luminance. The two elements types were identical in size but differed in sign and/or amount of contrast. Discrepancies between the observers' ratings of perceived segregation and the predictions of simple (linear) spatial-frequency and orientation channels models of texture segregation suggested adding nonlinear processes to the model. Complex channels (a rectification-type nonlinearity between two linear-filtering stages) can explain why some patterns made of center-surround elements segregate even though there is little energy at the spatial frequencies that differentiate the two textures. Complex channels cannot, however, explain the very poor segregation of "same-sign-of-contrast" patterns (where the luminances of the two element types were both far above or both far below the background). This second result might arise from a local nonlinearity preceding the channels and might be ascribed to retinal light adaptation except that it occurs at contrasts less than or equal to 25%! Alternatively, it might arise from normalization, which may result from intracortical inhibition. Some preliminary quantitative predictions were computed from two models, one incorporating complex channels and an early local nonlinearity, the other complex channels and normalization. With suitable choices of parameters, either model could account for the results. PMID- 1413558 TI - "Effortless" texture segmentation and "parallel" visual search are not the same thing. AB - If a region composed of one set of texture elements is effortlessly perceived on a background composed of another set, the texture segmentation is said to occur "preattentively". If the time required to find a target item among distractor items is independent of the number of distractor items, the visual search is said to occur with all items processed "in parallel". Effortless, preattentive texture segmentation and parallel visual search are sometimes assumed to be equivalent measures of the same parallel processing stage in the visual system. The demonstrations presented here show that this is not the case. Parallel processing can occur with stimuli that do not support effortless texture segmentation and vice versa. PMID- 1413557 TI - A reduction in stimulus duration can improve wavelength discriminations mediated by short-wave cones. AB - Virtually all visual discriminations become less accurate when either the luminance or the duration of the stimulus is reduced. An exception is found for wavelength discriminations near 460 nm, where an increase in either luminance or duration can cause the threshold to rise. For flashes of 100 msec or less, the critical variable is the total energy of the flash (i.e. the product of retinal illuminance and flash duration), and wavelength discrimination is optimal at an intermediate value; higher stimulus energy causes discrimination to deteriorate. To explain these findings we suppose that discrimination in this region of the spectrum is mediated by a channel that draws opposed signals from the short wavelength cones and from some combination of the middle- and long-wavelength cones, and that high stimulus energies cause saturation of this channel. PMID- 1413560 TI - Effects of lateral masking and spatial precueing on gap-resolution in central and peripheral vision. AB - The data made available by this experiment add two points to the information obtained by previous studies on eccentric vision and lateral masking. First, they demonstrate a clear effect of target-mask similarity on visual gap-resolution in eccentric vision: increasing target-mask similarity systematically decreases resolution performance. Second, spatial precueing has no effect on gap-resolution performance. One implication of this experiment is that with the present stimulus configurations, visual resolution should decrease much more strongly with eccentricity than it does with classical isolated or bar-masked optotypes. PMID- 1413559 TI - Detection of eyeshine by flashlight fishes of the family Anomalopidae. AB - Flashlight fishes of the family Anomalopidae live in clear tropical waters and are nocturnally active. They have luminescent organs located just below the pupils of their eyes. The relation of the luminescent organ to the pupil of the anomalopid eye is similar to that of the illumination and pupil system of the ophthalmoscope and identical to that of some photoretinoscopes. Indeed, one species of flashlight fish, Anomalops katoptron, actually moves its luminous organ away from its pupils in the process of occluding its light organ, making a retinoscopic-like movement. By photographing the eyeshine of a number of fishes with a photoretinoscope and by analyzing the optics of light organs of fish of the family Anomalopidae as well as the optics of reflecting eyes, we show under what light conditions and ranges flashlight fishes may reasonably be able to detect eyeshine from other fishes in the environment. Further, we suggest that flashlight fishes may be able to communicate with each other by altering the accommodation of their eyes. In such a communication system, the sender radiates no energy and communicates only with the interrogating receiver of the information. To our knowledge, this utilization of eyeshine, both for detection and for communication, is unique in the animal kingdom. PMID- 1413561 TI - Quantal noise and decision rules in dynamic models of light adaptation. AB - To evaluate some of the consequences of including probabilistic processes (e.g. quantal noise) in a computable model of light-adaptation dynamics, we considered the behavior of a general class of models. These models contain four stages: (1) early noise; (2) a deterministic filtering and gain-changing stage; (3) late noise; (4) a decision rule that is either an ideal (signal-known-exactly) detector or a peak-trough detector. With the ideal detector and without late noise, the observer's sensitivity as a function of mean luminance and temporal frequency is not affected by the filtering and gain-changing stage. Consequently, if the early noise is entirely quantal fluctuations, sensitivity will always be a square-root function of mean luminance and a uniform (flat) function of temporal frequency. This latter prediction is contradicted by all known data; either the ideal-detector is the wrong decision rule or sensitivity is almost always limited by sources of noise other than quantal fluctuations. With the peak-trough detector, however, with or without late noise, the observer's sensitivity as a function of temporal frequency does reflect the sensitivity of the low-level filtering and gain-changing stage. Late noise is needed, however, if the observer's sensitivity as a function of mean luminance is to go through both a square-root and a Weber region. Comparing these conclusions to similar work on the spatial frequency dimension highlights differences between the spatial and temporal frequency domains. Finally, on the basis of these analyses and evidence from the literature, we question whether quantal fluctuations limit visual sensitivity under any condition. PMID- 1413562 TI - Plan and operation of the NHANES I Epidemiologic Followup Study, 1987. AB - This report describes the plan and operation for the 1987 data collection wave of the Epidemiologic Followup to the first National Health and Nutrition Examination Survey (NHANES I). Tracing and data collection were conducted on 11,750 persons 25-74 years of age at NHANES I who were not known to be deceased in the 1982-84 and 1986 data collection waves of the NHANES I Epidemiologic Followup Study. PMID- 1413563 TI - Sample design: Third National Health and Nutrition Examination Survey. AB - This report presents a detailed description of the sample design for the Third National Health and Nutrition Examination Survey, 1988-94, including a brief description of research that led to the choice of the final design. The National Health and Nutrition Examination Survey (NHANES) is one of the major surveys of the National Center for Health Statistics, Centers for Disease Control. Information on the health and nutritional status of the noninstitutionalized population of the United States is collected through the NHANES household interviews and standardized physical examinations. PMID- 1413564 TI - [Changes in hemostasis in persons exposed to a change in atmospheric pressure]. AB - In eight healthy volunteers--four professional and four amateur divers--in a hyperbaric chamber simulated diving was implemented, corresponding to the most frequently encountered conditions of diving activities in Czechoslovakia. Throughout the trial indicators of haemostasis were investigated. Under the selected model conditions changes of the investigated parameters developed which can be considered indicators of a latent process of disseminated coagulation and the so-called syndrome of silent bubbles. PMID- 1413565 TI - [Air embolism]. AB - Air embolism is a dramatic event which threatens the patient's life during invasive therapeutic and diagnostic procedures. Immediately after establishment of the diagnosis treatment in a hyperbaric chamber should be started. The prognosis depends to a certain extent on how quickly the patient is transferred into a hyperbaric chamber. Treatment with hyperbaric oxygen is based on fundamental physical and physiological principles of the action of compressed air and the supply of a large amount of oxygen in a dissolved form into the ischaemic tissue beyond the obstruction. Installation of hyperbaric chambers in hospitals would make successful and prompt treatment of all cases of embolism possible, as well as of some other diseases indicated for hyperbaric oxygen therapy. PMID- 1413566 TI - [Hyperbaric oxygenation in the treatment of necrotizing fasciitis]. AB - The authors present the results of treatment provided to 11 patients with necrotizing fasciitis who were after a surgical operation and after administration of antibiotics treated in a hyperbaric chamber. A total of 8 patients (82%) recovered completely. The authors discuss the theory of action of hyperbaric oxygen on microorganisms and draw attention to the possible reduction of mortality of this serious disease when using hyperbaric oxygenation. The latter is considered an important auxiliary method which supplements surgical treatment, rational antibiotic therapy and in particular careful intensive care. PMID- 1413567 TI - [Treatment of ischemic cerebrovascular accidents with hyperbaric oxygenation]. AB - The authors present eleven year's experience with comprehensive treatment of patients who suffered an ischemic cerebrovascular attack. This comprises so called conventional treatment of cerebrovascular attacks and also hyperbaroxia, i.e. administration of oxygen under high partial pressure. The authors used a therapeutic pressure of 0.2 MPa for 90 minutes in individual exposures. Of 31 treated patients 23 improved, i.e. 76%; eight improved slightly, eight significantly and seven substantially. The condition of the remainder did not change. Hyperbaroxia should therefore be used everywhere where this method is available. PMID- 1413568 TI - [Estimation of energy utilization in patients based on catabolism of endogenous proteins]. AB - The authors describe their own methodical procedure used for estimation of energy requirements of patients with a defined nutrition. They ascribe importance to the quantitative assessment of the degree of catabolism of endogenous proteins the value of which they transform mathematically to calculate the catabolic factor with which they multiply the basal energy output calculated according to Harris Benedict equations. At the same time they take into account also the thermogenic action of nutrients. In 28 patients with gastroenterological diseases they confronted their own procedure with indirect calorimetry and theoretical calculations using Jabor's catabolic factor and Nejedly's formula. Differences between values of their own and other theoretical calculations, as compared with the results of indirect calorimetry, nor the results of Jabor's and Nejedly's calculation as compared with those of the authors did not reach the level of statistical significance. With regard to the assembled results the authors consider the suggested procedure for estimation of energy requirements as feasible, in particular when indirect calorimetry is not available. PMID- 1413569 TI - [Rapid continuous stimulation of the atrium (overdrive) in the treatment of refractory supraventricular tachycardia]. AB - In 71 patients, divided into four groups by the type of supraventricular tachycardia (SVT) during electrophysiological examination, 918 stimulations were implemented by the method of rapid continuous stimulation of the atria (overdrive) in order to interfere with a SVT paroxysm. In addition to characteristics of tachycardia the authors evaluated parameters of overdrive stimulation, i.e. the duration of the stimulation cycle (CL STIM), the ratio CL STIM/CL SVT, the number of stimuli required to terminate tachycardia (N STIM) and their mutual relations. In the group of atrioventricular reciprocal tachycardias (WPW, n = 17) the effectiveness was 50.4%, CL SVT 334 +/- 43 ms, the ratio CL STIM/CL SVT 78.3 +/- 12%, the median of N STIM 14 +/- 6. In the group of AV nodal tachycardias (AVNR, n = 26) the effectiveness is 53.1%, CL SVT 356 +/- 70 ms, CL STIM/CL SVT 77 +/- 8.6%. In the group of atrial tachycardias (AT, n = 5) the effectiveness was 62.3%, CL SVT 348 +/- 24 ms, CL STIM/CL SVT 73.7 +/- 7.5%, N STIM 6 +/- 4. In the group of atrial flutter (AFL, n = 23) the effectiveness was 9.2%, CL SVT 226 +/- 29 ms, CL STIM/CL SVT 84.5 +/- 8.2%, N STIM 22.5 +/- 9. The effectiveness of overdrive stimulation in AFL is significantly lower than in other groups of SVT. The regression correlation in the entire group of tachycardias for calculation of a suitable duration of CL STIM--0.855 x CL SVT- 28 (ms), the median number of stimuli N STIM 14 +/- 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413570 TI - [Hypercalciuria]. AB - Hypercalciuria is the cause of almost 20% of all secondary osteoporoses and in 23% these cases are associated with calcium urolithiasis. It is therefore necessary to search for these patients actively because their treatment with hydrochlorothiazide and amiloride is easy and highly effective. We must not be satisfied with the finding of hypercalciuria as the only cause of demineralization of bone, as several causes may combine in a single patient. Comprehensive treatment of osteopenia associated with hypercalciuria is relatively shorter and more successful than in other forms of secondary osteopenias. PMID- 1413571 TI - [Anti-idiotype antibodies to specific HLA. Incidence after bone marrow transplantation. Specificity and binding activity]. AB - Anti-idiotype antibodies against HLA specificities anti-HLA-A1, -A2, -A9, -A10, B7, -B8, -B12 were detected in sera of 13 patients after transplantation of bone marrow and in five patients who had no transplantation but many blood transfusions. They had a multispecific character, inhibited concurrently 4-5 of the mentioned HLA antibodies. HLA antibodies were not present in sera of these patients and did not develop even after treatment with dithiothreitol. It seems therefore that anti-idiotypic antibodies have also a IgG structure. The bond of anti-idiotype antibodies with HLA specificities was firm and maximal: they were not released after 24 hours incubation at room temperature and did not form bonds with other HLA antibodies with the same specificity. The authors discuss the importance of anti-idiotype antibodies against HLA specificities for the outcome of bone marrow transplantation and therapeutically successful thrombocyte transfusion. PMID- 1413572 TI - [Immunotyping of medullary and circulatory cells for prognostic evaluation of plasmacytoma]. AB - The authors discuss the prognostic impact of immunophenotyping of circulating lymphoplasmatic cells in the peripheral blood stream in patients with generalized plasmocytoma. From a group of 250 patients followed up from 1981 to 1991 they selected a sub-group of 70 patients where they evaluated in 1986-1991 after six month intervals the phenotype of medullary and circulating cells. They used the method of immunofluorescent detection of the presence of cytoplasmic Ig, the kappa-lambda index and phenotyping of antigens CD 9, CD 10, CD 20, CD 38, HLA-DR by monoclonal antibodies. In a longitudinal investigation of the survival period they revealed that the finding of circulating cells with signs of non differentiation (presence of antigen CD 10 detected by antibody CALLA, presence of antigens B 1 (CD 20), CD 9 on circulating lymphocytes) has a prognostic meaning suggesting shorter survival. There was a direct correlation between the increase of CALLA positive cells and CD 9 positive cells. The authors found also that release of the clonus with signs of immaturity was present when the disease developed into the aggressive stage. While the group of 250 patients had according to statistical analyses, when treated according to protocol VMCP/MOCCA, a median survival of 90 months, the median survival of the aggressive stage (with the plasmoblast and lymphoplasmocytic type resp.) was only 12 months. The authors emphasize the prognostic importance of immunological typing of heterogeneous plasmocytoma populations. PMID- 1413573 TI - [How knowledgeable are Czech physicians regarding risk factors for ischemic heart disease?]. AB - The authors present the results of an enquiry made by means of questionnaires in which 298 physicians participated. The enquiry was focused on risk factors of ischaemic heart disease. 41.8% physicians did not know their cholesterol level, 22.1% admitted that they smoked and another 17.8% were ex-smokers. Only half the physicians indicate dietetic treatment of hypercholesterolaemia when the blood level is 6.2 mmol/l. These and other data in the paper indicate that behaviour and knowledge of physicians as regards prevention of cardiovascular diseases most be substantially improved. PMID- 1413574 TI - [A case of systemic mastocytosis]. AB - The authors describe a rare case of systemic mastocytosis without skin infiltration. The first symptom were episodes of flushing in the face and upper trunk. From the case-history it was assumed that the condition had a several year's benign course, the diagnosis was established in the stage of malignant acceleration of the disease from bone marrow biopsy and liver biopsy. Atypical mastocytes displayed metachromasia with toluidine blue and positive naphthol-AS-D chloroacetate esterase. Symptomatic treatment with sodium cromoglycate reduced temporarily the frequency of flushing episodes, but it was not possible to arrest the increase of the mastocyte mass by cytostatic treatment. PMID- 1413575 TI - [Oxalosis in patients on regular dialysis therapy]. AB - The authors draw attention to the case of a 46-year-old man who developed after three years of regular dialyzation treatment three times a week the first manifestations of acquired generalized oxalosis. The oxalosis was most marked on the skin, skeleton, heart, and kidneys. Oxalosis was confirmed after eight years of dialysis after death by post-mortem and histological examination and microscopic detection of oxalate crystals. The authors recommend that as part of regular dialyzation treatment patients should not be given more than 100 mg ascorbic acid per day. Oxalates are also the end product of degradation of ascorbic acid and high doses may lead also to hyperoxalosis. Moreover deposits in some visceral organs, in particular the heart may cause clinical manifestations. In the authors patients they caused attacks of auricular flutter. Although these clinical manifestations develop only rarely, the latent form of acquired oxalosis is probably more frequent. PMID- 1413576 TI - [Angiodysplasia--a cause of severe hemorrhage in the gastrointestinal tract]. AB - The authors describe a case of relapsing severe haemorrhage from angiodysplasias localized in the small intestine in an eighty-year-old female patient diagnosed only after probatory laparotomy. They discuss the diagnostic possibilities in angiodysplasia of the gastrointestinal tract and how it can be influenced by therapy. Even after resection of the affected portion of the intestine the formation of new angiodysplasias must be foreseen in previously intact areas and those can be the source of further severe haemorrhage. PMID- 1413577 TI - [Psychosomatic aspects of arterial hypertension]. AB - In patients with labile hypertension aged 18-25 years the authors observed an increased sympathicoadrenal reactivity to mental strain caused by solution of a numerical square, parallel with a rise of diastolic blood pressure. Despite the fact that we do not know so far to what extent prolonged mental strain participates in the genesis and development of essential hypertension, the findings of the influence of some types of short-term strain on an acute rise of the blood pressure in hypertonic subjects should be used to modify the non medicamentous procedure in treatment of the disease. PMID- 1413578 TI - [Lipoproteinemia and diabetes mellitus]. AB - The author presents a review on lipoprotein metabolism in diabetes mellitus type I and II. He discusses the position in different lipoprotein classes--in particular LDL, VLDL, HDL and draws attention to the role of apolipoproteins and the association between lipoprotein disorders and complications of atherosclerosis in patients with diabetes of type I and II. The author deals also with the influence of genetic factors in the aetiology of hyperlipoproteinaemias. PMID- 1413579 TI - [Clinico-experimental prerequisites for the physiotherapeutic use of laser radiation]. AB - The paper reports clinical and experimental evidence in support of the validity of low-energy laser radiation in the treatment of chronic inflammatory and dystrophic diseases. Laser radiation was capable of improving the results of multimodality treatment. PMID- 1413580 TI - [A comparative analysis of the effect of low-intensity physical training on a bicycle ergometer, graded walking and drug therapy on the cardiovascular system of patients with stage-II hypertension]. AB - In contrast to standard bicycle exercise with moderate or submaximal effort, low effort exercises were employed by the author who studied their effect on cardiovascular system of stage II hypertension patients. They were males (n-126) aged 47.2 +/- 3.6 with the disease history of 8.4 +/- 1-9 years. Associated coronary heart disease was diagnosed in 82% of the patients. The test subjects were divided randomly into three groups: group 1 patients received drugs only, group 2 received drugs and exercised walking, group 3 received drugs and exercised on bicycle ergometer in the nonstrenuous regimen. It was found that exercise tolerance of the patients was different and depended on the hemodynamic type. Hypokinetic circulation patients showed the lowest exercise tolerance. Low effort bicycle exercise in addition to drugs is indicated for hyper- and eukinetic circulation patients. Walking is inferior to the bicycle exercise and can be recommended as a variety of nonpharmacological treatment of hypertension stage II. The combined effect of walking and chemotherapy produced the rise in cardiac capacity in the absence of the adequate increment in coronary blood flow, whereas bicycle exercise seems to enhance cardiac coronary circulation in hypertensive subjects. PMID- 1413581 TI - [The optimization of the sanatorium-health resort treatment of children with cardiovascular diseases]. AB - Functional systemic changes as compared to pretreatment characteristics served criteria of adaptation in children suffering from cardiovascular diseases. A load test with a single balneological procedure was used. Adaptation and compensation response proved useful as individual test loads to make therapy most efficient. PMID- 1413582 TI - [The treatment of patients with autonomic dyshormonal myocardial dystrophies at health resorts with nitrogen radon springs]. PMID- 1413583 TI - [The morphofunctional characteristics of the effect of centimeter-range microwaves on the rat liver depending on the exposure parameters]. PMID- 1413584 TI - [The dynamics of the indices of lipid peroxidation and mineral and lipid metabolism under the influence of UHF at different wave lengths in experimental chronic pancreatitis]. PMID- 1413585 TI - [The immunological and hormonal effects of combined exposure to a bitemporal ultrahigh-frequency electrical field and to decimeter waves at different sites]. AB - Bitemporal UHF electric field is shown to enhance glucocorticoid adrenal function unlike inhibition of the thyroid function suppressing a primary immune response (PIR) in the productive phase. The combined exposure to bitemporal UHF electric field and decimeter waves of the adrenals doubles glucocorticoid synthesis abolishing the inhibitory action of the UHF therapy on thyroid function resultant in much more suppressed PIR. Both modalities inhibit thymic production. Decimeter waves alone are less effective. The exposure of the thyroid to decimeter waves initiated PIR by 2.5-fold activation of medullar lymphocytes and by a 80% increase in the thymic function. No response was achieved in combined action on the thyroid of the electric field and decimeter waves. PMID- 1413586 TI - [The mechanism of the pathogenetic action of mud in treating the irritable bowel syndrome]. PMID- 1413587 TI - [Patient psychological characteristics after transient cerebral ischemia under the influence of physical factors]. AB - Seventy-eight patients with transitory cerebral ischemia (TCI) received a course of physiotherapy (68 subjects) or UHF therapy (10 control subjects). According to the authors' data TCI patients differed from hypertensive subjects as regards psychological status by predominance of psycho-organic and asthenic symptoms. It was found that neurological and mental statuses benefited from physiotherapy. The psychological status underwent less pronounced positive shifts. PMID- 1413588 TI - [The potentials of manual therapy in the neuromotor correction of the statokinetic disorders in infantile cerebral palsy]. AB - It is shown that manual therapy to abolish functional cervical and lumbar blocks is beneficial in reducing spasticity of the synergic muscles, biomechanic characteristics of the support and kinematic pace phases improve. Manual therapy in multimodality rehabilitation treatment of cerebral paralysis creates a functional base for neuromotor correction of a defective motor stereotype in these patients. PMID- 1413589 TI - [Methods for decontaminating balneological technical systems]. PMID- 1413590 TI - [The effect of the helium-neon laser on the cyclic nucleotide level in experimental hypodynamia]. PMID- 1413591 TI - [The action of laser radiation on the hydroxyl enzymatic system of the endoplasmic reticulum in hepatocytes]. PMID- 1413592 TI - [The organization of a network of pediatric health resorts and recreational institutions under the conditions of the new societal order]. PMID- 1413593 TI - [The organizational problems of therapeutic and conditioning physical exercise at the sanatorium-health resort stage of rehabilitation]. PMID- 1413594 TI - [A method of therapeutic massage in the sanatorium rehabilitation of patients with chronic bronchitis]. PMID- 1413595 TI - [The use of a UHF electrical field and dry-air carbon dioxide baths in the early periods after a cerebrovascular circulatory disorder and reconstructive operations on the major extracranial cerebral arteries]. PMID- 1413596 TI - [Interference therapy]. PMID- 1413597 TI - [The 70th anniversary of the Tomsk Research Institute of Health Resort Medicine and Physiotherapy]. PMID- 1413598 TI - [The valvular effect of the skin in electrophoresis with an alternating polarity of the electrodes]. AB - The effectiveness of iontophoresis by means of changing current direction was investigated on the skin of piglets using labelled potassium iodide (125I and 131I). Permeability without current served control. Percutaneous uptake was measured by blood levels and elimination of the isotopes from the urine. About a 200-fold increase of uptake was found in iontophoresis involving current change every 120 seconds and the concentration of 0.25 g/l of potassium iodide. Anions and cations may be pumped through the horny layer if the a-c frequency is less than 1/15 s-i. PMID- 1413599 TI - [The dynamics of the indices of myocardial autonomic regulation and contractile function in children with meteoropathic reactions undergoing health resort treatment and physical conditioning]. AB - The paper reports the results of examination of 93 patients with rheumatic fever and 42 healthy children aged 10-13 on treatment at Evpatoria sanatorium under different weather conditions. In unfavourable weather (hypoxic, spastic) vegetative regulation underwent changes dependent on clinical condition of the child and initial vegetative status. Sanatorium treatment and conditioning inhibited sensitivity to meteorological factors in rheumatic children by 60 and in healthy children by 83%. PMID- 1413600 TI - [Magnetotherapy in obliterating vascular diseases of the lower extremities]. AB - The investigators have developed a polymagnetic system "Avrora-MK-01" employing running impulse magnetic field to treat diseases of the leg vessels by the action on peripheral capillary bed. At a pregangrene stage a positive effect on peripheral capillaries was achieved in 75-82% of the patients treated. PMID- 1413601 TI - [The methods and efficacy of motor regimens in chronic nonspecific lung diseases at a family sanatorium]. AB - Conditioning exercises according to a specially designed schedule were performed at family sanatorium by the majority of 1757 patients with chronic nonspecific pulmonary diseases (CNPD). From those who completed the course of the conditioning, a pronounced effect was achieved in 20.7%, improvement in 78.4% of the patients. 0.9% of the test subjects did not respond, the disease progressed in 0.6% of the cases. PMID- 1413602 TI - [The dynamics of glucose homeostasis in non-insulin-dependent diabetics under the influence of mineral water intake]. AB - The paper presents time course changes registered in glycohomeostasis of patients suffering from non-insulin-dependent diabetes mellitus (NIDDM) as a result of a single or course intake of acidulous chloride hydrocarbonate sodium mineral waters. The treatment promoted immediate or delayed improvement in glycemia and insulinemia control, correction of imbalance of hormonal glycohomeostasis regulators (insulin, glucagon), enhancement of gastrinemia. The insulinotrophic effect varied with mineralization of the water, concentrations of bicarbonate and sodium ions. Water regimens were specified for NIDDM patients. PMID- 1413603 TI - [The assessment of the efficacy of bitemporal inductothermy in the combined treatment of obesity]. AB - To treat obese patients with arterial hypertension, bitemporal inductothermy was proposed. It was to be used in association with diet N 8 and drugs, improving trophism in brain cellular structures. The treatment led to reduction of body mass, normalization of arterial pressure without hypotensive drugs, improvements in lipidogram and physiological reaction of vasopressin-renin-aldosteron system. PMID- 1413604 TI - [The treatment of periodontitis by using a permanent magnetic field]. PMID- 1413605 TI - [The ultrasonic therapy of hypertensive patients]. AB - The collar zone of 40 subjects with essential hypertension stage II was exposed to continuous low-dose ultrasound (0.2-0.4 W/cm2). The course of 12-18 procedures reduced clinical symptoms. The decline in the maximal and minimal arterial pressure was statistically significant. Cerebral and central hemodynamics, sympathicoadrenal systems improved. PMID- 1413607 TI - [The extension of the use of physical methods of treatment to patients with disseminated sclerosis]. AB - The trial of various physiotherapeutic and balneological modalities (radon and turpentine baths, heparin electrophoresis, diadynamic current, acupuncture) in 317 patients with disseminated sclerosis showed their high therapeutical potential in the disease stage II-IV. The techniques and schedules need further investigations. PMID- 1413606 TI - [Oriented psychophysical action on patients with neurocirculatory dystonia]. PMID- 1413608 TI - [The analgesic efficacy of sulfur mud baths in treating rheumatic diseases of the soft tissues. A study using the double-blind control method]. AB - Changes in pain thresholds assessed in 16 trigger points were traced in two randomly selected groups of patients subjected to diluted mud baths in the presence or absence of sulfur compounds. Sulfur baths produced a significant lowering of pain sensitivity. The effect was augmenting with the number of procedures, the rise slowing down to the end of the course. PMID- 1413609 TI - [Medical gymnastics in the rehabilitative treatment of patients with locomotor injuries in combined and multiple trauma]. AB - The follow-up of 70 patients with trauma-related locomotor disorders proved that breathing exercises, vibratory massage, chest heparin electrophoresis, drug inhalations early after the injury can be effective in prevention and treatment of pulmonary complications. Transcutaneous neuroelectrostimulation noticeably enhanced the recovery of the locomotor function. PMID- 1413610 TI - [The experimental and clinical antianemia efficacy of the chalybeate waters from the Skhodnitsa springs]. AB - Low-mineral waters of Skhodnitsa [correction of Skhodnitsky] springs N 13 and N 15 rich in iron, silicon and manganese were tried for an antianemic effect. The latter was registered clinically and experimentally. PMID- 1413611 TI - [Electrostimulation in the rehabilitative treatment of urinary incontinence]. PMID- 1413612 TI - [The indications for the treatment at Truskavets health resort of different groups of patients with urological pathology]. PMID- 1413613 TI - [Immune suppression in local exposures to low-energy infrared laser radiation]. PMID- 1413614 TI - [The role of the macrophage-leukocyte component of the immune system in the mechanism of the desensitizing action of speleotherapy]. PMID- 1413615 TI - [The coronary and myocardial reserves of patients with ischemic heart disease under the influence of the peloid therapy of concomitant spinal osteochondrosis]. AB - Exercise test in coronary patients with angina of effort class II and III, painless cardiac ischemia reflected their increased coronary and myocardial reserves due to peloid therapy of cervical and thoracic osteochondrosis. As indicated by bicycle ergometry, angina of effort class III complicated by attacks of retrosternal pain at rest, circulatory insufficiency stage IIA, complex arrhythmia present contraindications for peloid application. PMID- 1413616 TI - [The dynamics of the lipid metabolic shifts during the naphthalan therapy of patients with arteriosclerosis obliterans of the vessels of the lower extremities]. PMID- 1413617 TI - [Inhalation aerosol therapy: the rules and allowable errors]. PMID- 1413618 TI - [A radon beta applicator]. PMID- 1413619 TI - [The microbiology of potable mineral waters]. PMID- 1413620 TI - [Structural and functional features of the erythrocyte membrane cytoskeleton]. PMID- 1413621 TI - [Modulation of lipid peroxidation by biogenic amines in model systems]. AB - Specific effects of serotonin, histamine, noradrenaline and tyramine on the rate of lipid peroxidation were studied in model systems by means of measurement of malonic dialdehyde and Schiff base concentration as well as of kinetics of O2 consumption. Alterations in the lipid peroxidation rate in the presence of biogenic amines occurred dissimilarly depending on localization of oxidation substrates either in bilayer membranes or in micellar solution. The antioxidative effect of serotonin was the most pronounced as a result of its ability to react with lipid peroxidation radicals. PMID- 1413622 TI - [Change in the opioid peptide level in the heart and blood plasma during acute myocardia ischemia complicated by ventricular fibrillation]. AB - After occlusion of the anterior descending coronary artery content of opioid peptides was increased 2-3-fold in blood plasma of all the rats with and without ventricular fibrillation. Content of Leu-enkephalin was decreased in ischemic and non-ischemic regions of myocardium under conditions of ventricular fibrillation. At the same time, concentration of Met-enkephalin in myocardium was increased in the acute ischemia independently on the effect of fibrillation. Synthetic enzyme resistant derivative of Leu-enkephalin, administered before acute myocardial ischemia, prevented a decrease in the ventricular fibrillation threshold caused by the occlusion. Alteration of the Leu-enkephalin content in heart tissue appears to be importance in pathogenesis of ventricular fibrillation developed after acute myocardial ischemia. PMID- 1413623 TI - [Deamination reaction of biogenic amines and other nitrogen compounds during the long-term influence of ethylenediamine in an experiment on rats]. AB - Activity and substrate specificity of monoamine oxidase (MAO) were studied in tissues of rats inhaling low concentrations of ethylene diamine for a long time. While the activity of MAO-A (serotonin as a substrate) was decreased in brain, functions of the enzyme were altered: the enzyme acquired the ability to deaminate glucosamine, which is not a substrate of MAO under normal conditions. Ethylene diamine-dependent modification of MAO was responsible for alterations of the enzyme catalytic properties involved in oxidation of substances with specific biochemical functions. A new drug diethon as well as ionol, pyrazidole and ascorbic acid were used in attempts to normalize the MAO properties; ionol proved to be the most effective compound. Detection of alterations in the MAO catalytic properties, developed after influence of the chemical factor at very low concentrations but without symptoms of toxicosis, may be used as a sensitive test for evaluation of early steps of ethylene diamine-produced intoxication. Ionol may be used for pathogenetic prophylaxis of ethylene diamine caused intoxication. PMID- 1413624 TI - [Derivatives of 4-phenylpiperidine as substrates of rat brain monoamine oxidase]. AB - A rate of utilization of 4-phenyl piperidine and its 12 derivatives by brain monoamine oxidase (MAO) was studied as compared with typical neurotoxin 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The enzyme was isolated from P2 synaptosomal fraction of brain corpus striatum of Sprague-Dawley rats. 10 drugs were oxidized in the MAO-catalyzed reaction with the rate close or similar to the MPTP oxidation while 6 of them exhibited the neurotoxic effect. Analysis of MAO inhibition, using 1 microM of chlorgyline and/or deprenyl, enabled to evaluate the contribution of MAO-A and MAO-B forms to utilization of 1 mM content of the substances studied. MAO-B was shown to oxidize preferably the drugs radicals of which were substituted at 3rd position of the piperidine ring, while MAO-A preferred the derivatives with radical substitution at 4th position. The rate of substrate oxidation was decreased distinctly after introduction of complete substituents into the 3rd and 4th positions of the nitrogenous heterocycle; at the same time, presence of cyclic fluorine-containing structures increased the rate of utilization, similar to that of MPTP oxidation. Derivatives of 4-phenyl piperidine, which contained in a number of drugs, were oxidized in the MAO catalyzed reactions and might exhibit direct- or side-neurotoxic effects. PMID- 1413625 TI - [Natural modulators of the function of the amine oxidase system in the body]. AB - In cerebrospinal fluid (CSF) obtained from patients with chronic alcoholism natural modulators of monoamine oxidase (MAO) activity, containing in human mitochondrial and microsomal fractions or in rat brain mitochondria, have been found. These modulators, which were previously unknown, did not affect the activity of partially purified diamine oxidase from human placenta with 14C putrescine as a substrate. The MAO modulators from CSF were thermostable (during 3 min at 100 degrees), penetrated through dialysing membrane thus differing from high molecular modulators of MAO previously described. In the system containing membrane bound MAO from human placenta, where the MAO-A is predominating, the modulators studied mostly inhibited deamination of 14C-serotonin. However, in the system containing membrane bound MAO from rat brain with prevalence of the MAO-B, the modulators from human CSF caused either inhibition or stimulation of oxidative deamination of 14C-serotonin or 14C-beta-phenylethylamine used as substrates. The modulators studied were not similar to tribulin (isatin) or quinolinic acid in their effects on catalytic properties of the amine oxidases investigated. PMID- 1413626 TI - [Effect of biogenic amines on glycogen degradation in isolated rat hepatocytes]. AB - Serotonin and tyramine affected dissimilarly the enzyme activity involved in degradation of glycogen in isolated rat hepatocytes. Serotonin inhibited hydrolytic enzymes acid alpha-glucosidase, alpha-amylase and amylo-1,6 glucosidase but activated phosphorylase inducing a decrease of glycogen content in cells. Tyramine inhibited acid alpha-glucosidase and amylo-1,6-glucosidase, did not affect the alpha-amylase and phosphorylase activities and increased content of glycogen in cells. Tyramine may be used as stimulator of glycogen accumulation in liver cells. PMID- 1413627 TI - [Activity of antioxidant protection enzymes and content of lipid peroxidation products in blood serum and cerebrospinal fluid in patients with ischemic brain disease]. AB - Activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase as well as content of diene conjugates and malonic dialdehyde were studied in blood serum and cerebrospinal fluid of patients with transitory ischemia, small ischemic insult, ischemic insult of middle severity and with severe ischemic insult without lethality within 1-2, 7-8 and 14-15 days of diseases. Content of lipid peroxidation products and activity of antioxidant enzymes were decreased in the biological fluids studied in all the forms of brain circulation impairments within early periods of pathology. These patterns tend to normalization within 14-15 days. The rate of biochemical alterations corresponded highly to severity of impairments developed and these patterns may be used for diagnostic and prognostic purposes. PMID- 1413628 TI - [Specifics of changes in various groups of enzymes in rat cerebral cortex after interstrain transplantation of embryonal nerve tissue]. AB - Embryonal nervous tissue from Wistar rats was transplanted into male rats of Wistar and August strains. Activity of eight enzymes belonging to various systems was estimated in brain cortex of rats recipients within 36 days after the transplantation. Lactate dehydrogenase, alanine aminotransferase, acid phosphatase, 5'-nucleotidase, ATPase and aldolase exhibited the dissimilarly decreased rate of activity in brain cortex of Wistar rats after transplantation as compared with the enzymatic activity in intact animals of this strain, while activity of alkaline phosphatase and esterases hydrolyzing alpha-naphthyl acetate was increased. Activation of almost all the enzymes studied was found within 36 days in Wistar rats after the transplantation. The rate of activity of zonal esterase isoenzymes was higher in brain cortex of August rats after transplantation of embryonal nervous tissue from Wistar strain as compared with that of Wistar to Wistar rats transplantation. The data obtained suggest that tissues of donors affected definitely the enzymatic activity in brain cells of rats-recipients as activity of most enzymes studied was higher in brain cortex of donors as compared with that of recipients. PMID- 1413629 TI - [Current concepts on the biogenesis of lysosomal proteins in normal condition and in disease]. PMID- 1413630 TI - [Metabolism of neuronal and neuroglial phospholipids in seizures]. AB - Metabolism of individual phospholipids was studied in neurones and neuroglia under conditions of convulsions caused by picrotoxin administration. Metabolic activity of all the phospholipids studied was increased in neuronal membranes under extreme conditions of convulsive attacks. The rate of metabolism of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin was increased 2 2.5-fold approximately. The most distinct alterations of metabolic activity were observed in the fraction of minor phospholipids: specific radioactivity of phosphatidylserine was increased 10-fold and phosphatidylinositol--16-fold. Metabolism of phosphatidic acid and lysophosphatidylcholine was elevated more than 15-fold. Convulsions exhibited the most distinct effect on metabolism of phosphatidylinositol and phosphatidylserine in neuroglia cells. As distinct from neurones, metabolism of phosphatidyl choline and sphingomyelin was not markedly altered in neuroglia. Similar metabolism and universal cell response, carried out via phospholipids, appear to occur in the system neurone-neuroglia. PMID- 1413631 TI - [Antioxidant effect of dimethyl sulfoxide in acute liver injury by carbon tetrachloride]. AB - After subcutaneous administration of dimethyl sulfoxide into rats with toxic, tetrachloromethane-produced impairment of liver tissue, lipid peroxidation was effectively inhibited in hepatocytes and the state of anti-oxidation system was improved. Antioxidative properties of dimethyl sulfoxide were shown also in vitro. PMID- 1413632 TI - [Alcohol and atherogenesis: effect of low and high doses of ethanol on rat blood cholesterol]. AB - Alterations in content of cholesterol and specific radio-activity of erythrocyte lipoproteins were studied in rats after administration of labelled sterol under conditions of acute and chronic influence of low 0.6 g/kg and high 4.0 g/kg doses of ethanol. Both these doses caused a decrease in content of high density lipoproteins (HDL) after single ethanol administration, while content of apoB containing lipoproteins as well as binding of labelled sterol with erythrocytes were elevated after long-term ethanol treatment. Atherogenicity index was increased after single and chronic administration of either low or high doses of ethanol. In chronic administration of low doses of ethanol specific radioactivity of HDL was decreased, thus suggesting that cholesterol acceptor function of these particles was lowered. PMID- 1413633 TI - [Prostacyclin-thromboxane system in children and adolescents with a high risk of developing ischemic heart disease]. AB - Studies of the prostacyclin-thromboxane system in children and juveniles of 7-18 years old with hereditary ischemic heart disease demonstrated that the hereditary factor proved to be of importance for the system state. Alterations of prostanoids in these children and juveniles were related to atherogenesis development, particularly to hyperproduction of thromboxane A2, whereas patterns of the system studied varied depending on sex and family history. PMID- 1413634 TI - [Systemic and regional hemodynamic in rats after use of 5-methoxytryptamine: mechanisms of "pharmacological adaptation" to hypoxia]. AB - Effects of 5-methoxytryptamine (5-MOT) on parameters of systemic and regional hemodynamics were studied in awake Wistar rats. Arterial pressure and pulse were measured using a direct procedure. Content of systolic blood and volume rate of blood flow in 12 vascular zones were estimated by means of the radioactive microsphere technique. The microspheres were inoculated in left heart ventricle under free conditions before, within 30 min and after termination of the "pharmacological training". Single intraperitoneal administration of 5-MOT, 25 mg/kg, led to increase in total peripheral resistance by 67% and in cardiac index by 34%. The rate of blood flow was decreased in skin, spleen, kidney and testicular tissues, while it was increased in heart and adrenal glands. "Pharmacological training", carried out within 9 days with daily administration of 5-MOT 25 mg/kg, resulted in a decrease in total peripheral vascular resistance by 46%, while cardiac index was increased by 97%; blood flow rate was increased in brain, stomach, heart and diaphragm. PMID- 1413635 TI - [Effect of essential phospholipids on intensity of lipid peroxidation in the myocardium in experimental post-hypoxic reoxygenation]. AB - Correction of the lipid peroxidation rate using essential phospholipids was studied. The phospholipids were used in protection of heart tissue in experimental posthypoxic reoxygenation. Administration of essential phospholipids into the rats during myocardium reoxygenation led to an increase in activity of superoxide dismutase. The drugs containing essential phospholipids may be used in clinical practice for treatment of the impairments when elevated lipid peroxidation occurred. PMID- 1413636 TI - [Determination of procollagen type III aminopropeptide by a solid phase method using antibodies conjugated with peroxidase or protein A labelled with radioactive iodine]. AB - A solid-phase assay was developed for estimation of procollagen III aminopropeptide which involved both immunoenzymatic and radioimmune procedures. The assay did not require the iodine-labelled aminopropeptide, while content of the antigen was estimated using the conjugate of secondary antibodies and peroxidase or iodine-labelled protein A. Substitution of the protein A for the antibodies conjugate and peroxidase enabled to abolish the radioactive materials use. PMID- 1413637 TI - [Determination of cholesterol esterase activity using micro-thin layer chromatography]. AB - A procedure is developed for estimation of the cholinesterase activity in biological materials immediately on the plates for micro-thin-layer chromatography using a chamber of original construction. The procedure involved incubation of cholesterol esters, used as substrates and biological materials containing the enzyme, directly on the chromatographic plates in the chamber and the subsequent chromatography of the hydrolysis products. The enzymatic activity was calculated on the basis of the decrease in the substrate content per min per mg of protein. The procedure is simple, convenient; it allows to vary the incubation time and to estimate the enzymatic activity in minimal samples of the biological material using only small amounts of reagents. PMID- 1413638 TI - [Changes in phosphatidylinositol content in patients with myocardial infarct]. AB - The changes of phosphatidylinositol content in blood of patients with myocardial infarction was studied. A procedure is developed for multiple estimation of phosphatidylinositol content within short-time intervals which enabled one to obtain additional data on the functional state of biomembranes. In the clinical practice the data obtained may be used for diagnosis and evaluation of efficiency of ischemic heart disease treatment. PMID- 1413639 TI - [Change in content of fatty acids in rabbit brain hemispheres in experimental concussion]. AB - Content of fatty acids in rabbit brain hemispheres in dynamics of experimental brain concussion was estimated by means of gas liquid chromatography. Content of fatty acids was increased within 15 min after experimental brain concussion and then it decreased reaching minimal values within 7 days. The phenomenon observed is a pathogenetically important factor in the traumatic disease. PMID- 1413640 TI - [Effect of alpha-tocopherol on lipid peroxidation in the liver in acute blood loss]. AB - The effect of single administration of alpha-tocopherol at a dose of 50 mg/kg on lipid peroxidation, content of alpha-tocopherol in liver tissue and on the activities of some enzymes in rat serum was studied under conditions of acute blood loss. The rate of lipid peroxidation in liver tissue and activities of aspartate- and alanine-transferases in blood serum were increased while content of alpha-tocopherol in liver tissue was decreased under the conditions of acute blood loss. These effects were abolished after tocopherol administration. Use of alpha-tocopherol as an antioxidant drug proved to be suitable for pathogenetic correction of metabolic impairments in acute blood loss. PMID- 1413641 TI - [Lipid peroxidation upon the use of omega-3 polyunsaturated fatty acids in the treatment of hypertension and ischemic heart disease]. AB - Anti-atherosclerotic diet containing 10 or 20 g of ichthyenic oil, used for treatment of 29 patients with cardiovascular diseases, caused an increase in content of polyunsaturated omega 3 fatty acids species in the patients erythrocyte membranes; this pattern may be used as a sensitive criterion of evaluation of the diet fatty component effect. Despite an increase of oxidation potential substrates in tissues, elevation of malonyl dialdehyde in blood plasma and hemolysis of erythrocytes in presence of H2O2 were not observed. This suggests absence of lipid peroxidation induction in adequate consumption of antioxidants. PMID- 1413642 TI - [The effect of diets containing omega-3 polyunsaturated fatty acids on biochemical indicators and the fatty acid composition of the cell membranes in patients with ischemic heart disease and hereditary hyperlipidemia]. AB - A decrease in content of total cholesterol, triglycerides, fibrinogen, and atherogeneity index as well as increase in fibrinolytic activity and prolongation of the hemorrhage time were observed in blood serum of 20 patients with ischemic heart disease and hyperlipidemia of the IIa and IIb types maintained on anti atherosclerotic diet containing 20 g of ichthyenic oil within 4 weeks. Relative content of polyunsaturated fatty acids omega 6 was decreased while the content of omega 3 fatty acids was distinctly increased in erythrocytes and blood platelets membranes, thus demonstrating the high efficiency of ichthyenic oil. PMID- 1413643 TI - [Specific relationships of the content of iron, transferrin, ceruloplasmin and malondialdehyde in rat blood in various types of wound healing processes]. AB - Correlation between parameters of iron metabolism and the antioxidative system activity was studied in blood of 220 Wistar rats with simulated aseptic and infectious types of wound healing. Deposition of iron and stability of the anti oxidation system were impaired in purulent complication of wound healing. At the same time, a high correlation between the patterns studied was detected in aseptic form of healing, suggesting distinct co-ordination between the antioxidative system components. Approaches to the correction of the impairments observed are discussed. PMID- 1413644 TI - [Features of the structure and fatty acid composition of serum albumin in experimental myocarditis]. AB - Properties of animal serum albumin transport and its structure were studied in experimental myocarditis. The data obtained suggest that impairments in myocardium were of chronic and recurring type. The albumin exhibited a high structure-functional variability. PMID- 1413645 TI - [Features of the lipid peroxidation process and antioxidant activity of white rats in extreme, multi-stage supercooling]. AB - High content of polyenic fatty acids, slight increase in antioxidative activity and decrease in content of malonic dialdehyde (MDA) in rat myocardial tissues were observed in supercooling. The data obtained suggest that intensive oxidation of fatty acids occurred in the tissues, which may be essential for synthesis of biologically active substances involved in development of resistance to supercooling. Multiple supercooling caused an opposite effect in lung tissue: saturation of lipids was increased, antioxidative activity was maintained on the level similar to the control values, while content of MDA was markedly increased apparently due to destruction of metabolic products penetrating from other tissues. The dissimilar impairments of lipid metabolism were detected in liver tissue, where multiple supercooling did not alter the rate of lipid saturation, antioxidative activity was unaltered and content of MDA was as low as in the control animals. PMID- 1413646 TI - [Age changes in brain monoamine oxidase in mice from four lines]. AB - Mice of strains CC57/Br, A/He, C3H/He and CBA/Lac were studied at the age of 1, 2, 3, 4 and 5 months old. Activities of monoamine oxidases A and B (MAO A and MAO B) were increased in brain tissue of all the mice strain studied with ageing, although not simultaneously and dissimilarly. The ratio MAO A/MAO B approximated to 1.0 in old animals. At the age of 1 month old the MAO A/MAO B ratio was more than 1.0 in brain stem of mice of CC57/Br and C3H/He strains as well as in hemispheres of mice of A/He and CBA/Lac strains. In mice of A/He strain the MAO A/MAO B ratio exceeding 1.0 maintained within the first three months. Possible correlation between the elevated MAO A/MAO B ratio and high sexual activity of the A/He strain mice is discussed. PMID- 1413647 TI - [Multiple forms of monoamine oxidase in the growing human placenta]. AB - A ratio between two types of monoamine oxidase (MAO) was studied in the mitochondrial fraction of growing human placenta: MAO-A which is predominant in the tissue and the minor MAO-B. Activity of MAO-A with serotonin as a substrate was statistically distinctly lower (by 22%) in placenta within early periods of pregnancy as compared which the mature placenta during the delivery time. In the growing placenta activity of MAO-B with benzylamine as a substrate reached 365% of the MAO-B activity in the mature placenta. The ratio between MAO of the A and B types was altered during pregnancy as shown by inhibitory analysis, carried out using selective inhibitors of the MAO-A and -B types--Lilly 51641 substance and deprenyl as well as with semicarbazide as an inhibitor of benzylamine oxidase. At the early periods of pregnancy the rate of placental MAO-B oxidative deamination of benzylamine was distinctly higher as compared with that during the delivery act. At the same time, content of semicarbazide-sensitive benzylamine oxidase was increased during the delivery period. Possible biological significance of alterations in the amine oxidases ratio in the growing placenta is discussed considering the known property of the MAO-B inhibitor pargyline to cause abortion within early periods of pregnancy. PMID- 1413648 TI - [Placental-renal prealbumin: immunochemical identification, physico-chemical characteristics and affinity chromatography on immobilized steroids]. AB - A protein with prealbumin mobility and MW of 40 kD was identified in early placental tissue. Using immunodiffusion analysis the protein was also detected in fetal and adult kidney tissues, in urine of donors and pregnant women and in amniotic fluid. The protein was termed placenta-kidney prealbumin (PKPA). During affinity chromatography on immobilized steroid hormones, PKPA was bound to testosterone and was not bound to diethylstilbestrol. PMID- 1413649 TI - [Physico-chemical, immunochemical, and biological activity of prolactin from human amniotic fluid]. AB - Highly purified preparation of prolactin with molecular mass 23 kDa, which is the main form of the hormone in human amnionic fluid, was isolated from the fluid using gel filtration on Sephadex G-100, chromatography on DEAE-Sepharose, concanavalin A Sepharose, CM-cellulose. Physico-chemical, immunochemical and biological properties of the amnionic prolactin were studied as compared with those of hypophyseal hormone. Properties of the hormonal forms isolated from both these tissues were similar. The glycosylated form of prolactin with molecular mass 25.0 kDa was detected either in amnionic fluid or in hypophysis. PMID- 1413650 TI - [Physico-chemical properties of the thrombolytic compound longolytin]. AB - A preparation exhibiting high fibrinolytic activity and ability to activate plasminogen was isolated from cultivation medium of Arthrobotrys longa. Homogeneous protein, obtained after gel filtration on Sephadex G-100, had molecular mass 28,600, pI-3.68-3.74, optimum activity at pH 6.0-9.0 and temperature optimum at 37 degrees. The enzyme proved to be serine proteinase as shown by analysis using inhibitors; it required thiol groups. PMID- 1413651 TI - [Features of metabolic disorders in the liver during morphine poisoning of various duration]. AB - Administration of morphine into rats at a dose of 30 mg/kg within 6 days led to a decrease in total rate of tRNA aminoacylation in liver tissue. Content of lactate, pyruvate, malate and alpha-ketoglutarate was decreased within 6 days long course of morphine administration, while content of lactate was only altered after 5 weeks of the intoxication. Adaptation reactions appear to be increased with time in long-term intoxication with morphine. PMID- 1413652 TI - [Change in the lipid composition of rat tissues in hyperthermia of varying degree]. AB - The most typical alteration of membrane phospholipids in rat tissues in acute hyperthermia was an increase in content of sphingomyelin and phosphatidylinositol. The increase in phosphatidylinositol appears to occur as a result of unspecific effect of hyperthermia on the cells, while the increase of sphingomyelin is apparently important for stabilization of membrane structure. Indirect data were obtained on increase in membrane liquidity during thermic shock. PMID- 1413654 TI - [Effect of alpha-acidic glycoprotein on oxyproline metabolism in experimental thermal trauma]. AB - alpha 1-Acid glycoprotein, isolated from human blood plasma, was shown to accelerate healing of burn wounds in rats and to increase daily urine excretion. The glycoprotein restricted an elevation of the peptide-bound hydroxyproline in blood plasma, decreased the ratio between peptide-bound and free hydroxyproline within all the periods of experiment during 3 weeks as well as stimulated hydroxyproline excretion with urine at the step of active reparation of burn wounds. The glycoprotein appears to protect connective tissue metabolism in burns. PMID- 1413653 TI - [Molecular mechanisms of damage to fractionated liver chromatin by tetrachloromethane]. AB - Impairing effects of tetrachloromethane on genetic apparatus were shown to consist in its high affinity and binding to transcriptionally active fraction of chromatin and subsequent destruction of DNA. As a result of the impairment the density of the chromatin fraction was increased which expressed as elevated stability to hydrolysis by endogenous nucleases. At the same time, content of single-stranded structures enriched with proteins was increased in the DNA of the transcriptionally active fraction of chromatin. Two dissimilar properties were detected in the fraction of impaired chromatin from the poisoned animals: increase of density in the chromatin fraction accompanied by insensitivity to S1 nuclease, which was detected after denaturation of chromatin and slight relaxation of apparently supernucleosome structures where content of sites, sensitive to short-term treatment with DNAase I, was increased. The hypothesis of the tetrachloromethane toxic effect on genetic apparatus is considered, according to which lipid moiety of chromatin and activation of lipid peroxidation are of definite importance in effects of the xenobiotic on chromatin. PMID- 1413655 TI - [Effect of middle molecular weight peptides, isolated from blood of intact dogs and those with burns, on proteolysis in mouse tissue]. AB - The median molecular-weight peptides (MMP), detected in blood of patients with burns and in that of experimental animals with burns, were shown to affect various systems in vivo. The MMP from the blood of intact dogs and of the animals with burns exhibited the modifying effect on proteolysis within acid and neutral pH ranges in liver and brain tissues of mouse. The MMP appears to be involved in the regulation of proteolysis both in normal state and in burns. PMID- 1413656 TI - [Molecular types of breast milk triacylglycerols at various stages of lactation]. AB - The composition of individual triacylglycerols was studied in women milk in various periods of lactation. The spectra of triacylglycerols were studied in the early lactation milk, in the mature milk and in the late lactation milk using a method of "main components", the program of "immediate neighbour" as well as by construction of graphic plot (by means of a set "Statgraphics"). The methods of calculation used enabled one to find great differences in the triacylglycerol spectrum of mature milk as compared with those of milk in the early and late periods of lactation. PMID- 1413657 TI - Gift or good? A contemporary examination of the voluntary and commercial aspects of blood donation. AB - The safety and ethical aspects of blood donation are examined in the light of current legislation and practice. The advantages and disadvantages of voluntary and paid donation are looked at in view of recent data concerning risk factors in various potential donor groups. It is concluded that voluntary, non-remunerated blood donation remains the safest and most ethical means of securing the blood supply. PMID- 1413658 TI - Studies in red blood cell preservation. 6. Red cell membrane remodeling during rejuvenation. AB - The purpose of this study was to examine whether vesiculation of RBC plays a significant role in their rejuvenation. Outdated units of Adsol blood, were divided into two aliquots and incubated with equal volumes of a solution of 100 mM pyruvate and inosine, 103 mM phosphate and 5 mM adenine (PIPA) or 0.9% saline. Following 1 h incubation, vesicles were isolated from the supernatants and quantitated for hemoglobin content. Restoration of RBC ATP, 2,3-DPG, morphology, and osmotic fragility after rejuvenation was satisfactory. The postrejuvenation mean corpuscular volumes (88.2 +/- 6.9 fl) were significantly lower (p less than 0.001) than the prerejuvenation (94.6 +/- 6.8 fl) and control (104.0 +/- 7.3 fl) volumes. The hemoglobin shed in vesicles during rejuvenation was significantly greater than in the saline controls (0.44 +/- 0.31 vs. 0.18 +/- 0.10 mg/dl RBCs; p = 0.026). These data suggest that the decreased MCV following rejuvenation is in part due to membrane loss in exocytic vesiculation. PMID- 1413659 TI - Bone marrow fractionation by the haemonetics system: reduction of red cell mass before marrow freezing, with special reference to pediatric marrow volumes. AB - For purposes of freezing autologous marrow or transplants of allogeneic marrow with major ABO blood group incompatibility, 54 freshly harvested bone marrows from children of 7-65 kg of weight were depleted of their red cells with the Haemonetics V50 system. The marrow volumes ranged from 230 to 1,145 ml, with 17 small (200-399 ml), 18 intermediate (400-799 ml) and 19 large (800-1,200 ml) volumes. After processing, the median recoveries were: volume 24%, red cell mass 18%, and nucleated cells 75%. In the small marrow volume group, a good nucleated cell recovery was achieved at the expense of red cell depletion. The colony forming units, granulocytes-macrophages (CFU-GM) were normal after thawing of processed, cryopreserved marrows, and good engraftment of both allogeneic and autologous marrows were achieved. We conclude that marrow processing with the Haemonetics V50 system results in adequate red cell depletion and good nucleated cell recovery without open-air contact of marrow or excessive time consumption. For small marrow volumes, however, the red cell depletion was suboptimal, and a bowl size smaller than 125 ml is desirable for pediatric use. PMID- 1413660 TI - Transfusion results of filtered and subsequently stored random platelet suspensions prepared from buffy coats. AB - There is almost general agreement that removal of leukocytes from blood components reduces the incidence of HLA-antibody formation and refractoriness to random platelet transfusions. Recently filters have become available, which are able to reduce leukocyte contamination in platelet suspensions with acceptable platelet loss. We evaluated a cellulose acetate (CA) and a polyester (PE) filter, and stored buffy coat-derived platelet suspensions after filtration. Both filters are effective for the removal of leukocytes to levels below 5 x 10(6) per transfusate. For the CA filter, platelet recovery was 73 +/- 13% yielding 256 +/- 53 x 10(9) platelets per transfusate from 6 donors. For the PE filter, platelet recovery was 90 +/- 9% and 327 +/- 51 x 10(9) platelets per transfusate. When a loading dose of less than 5 x 10(8) leukocytes was applied, 98% of the CA filtered suspensions and 100% of the PE-filtered suspensions contained less than 5 x 10(6) residual leucocytes. In 123 patients transfusion results of CA-filtered platelet suspensions stored for 72 h, were compared with those obtained by non stored, non filtered, random platelet suspensions which had been leukocyte depleted by differential centrifugation. Platelet increments 1 and 20 h after transfusion showed no statistical difference between CA-filtered platelet transfusions stored for 72 h and non-stored, non-filtered platelet transfusions. In a new cohort of 117 patients, two filters and various postfiltration storage times were compared. Using both filters, the 1-hour posttransfusion increments decreased to approximately 60% after 96 h of storage compared to results of storage periods of 72 h or less.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413661 TI - Red cell and platelet concentrates from blood collected into half-strength citrate anticoagulant: improved maintenance of red cell 2,3-diphosphoglycerate in half-citrate red cells. AB - This study confirms previous work suggesting equivalent in vitro properties in blood components prepared from donations collected into half-citrate preservative (HCPD) compared to components derived from donations collected into standard citrate-phosphate-dextrose (CPD) preservatives. In addition, red cell products harvested from HCPD donations showed significantly improved maintenance of pH over storage, and this was reflected in improved maintenance of intracellular 2,3 diphosphoglycerate (2,3-DPG). This effect was observed in whole blood and in red cells suspended in a phosphate-containing additive solution (Tuta AAS). Collection into HCPD also improved 2,3-DPG maintenance in red cell concentrates processed following an 18-hour hold at 22 degrees C. These improvements were less pronounced in red cells suspended in a non-phosphate-containing medium (Fenwal Adsol) in which a higher pH was maintained even in units collected in CPD. Platelets harvested from HCPD blood and suspended in plasma showed equivalent quality to platelets from standard donations. Some deterioration of platelet properties was observed when HCPD platelets were stored in a non-citrate synthetic medium. Together with data indicating improved coagulation factor stability, these results suggest that collection into HCPD improves stored blood quality and may also allow logistical benefits in blood component preparation. PMID- 1413662 TI - Severe haemolytic disease in an infant born to an Rh(null) proposita. AB - A 35-year-old Brazilian woman (gravida 4, para 2) was delivered of a severely anaemic child whose cord red blood cells had a strongly positive direct antiglobulin test and who required two exchange transfusions within 24 h of birth. Because of the emergency of the situation and the lack of a local immunohaematology reference laboratory, the phenotype of the mother and the specificity of the relevant antibody could not be determined. Hence, compatible blood was not immediately available and the infant had to be given repeated exchange transfusions with incompatible group 0 Rh-negative blood. The infant is now healthy and thriving. The mother's red cells were subsequently found to lack all the antigens of the Rh system, and her serum reacted with all red cell samples except those of two unrelated Rh(null) individuals. Her serum gave high titres (i.e. 1,024-4,096) by the indirect antiglobulin test against red cells of normal Rh phenotype, as well as against cells with partially deleted Rh phenotypes (titres = 128-512 with -D-/-D- and .D./.D. samples, respectively), and was extremely active in antibody-dependent cell-mediated cytotoxicity and monocyte monolayer assays against red cells of normal Rh phenotypes. PMID- 1413663 TI - Granulocyte serology findings in juvenile symptomatic idiopathic autoimmune neutropenia using a multiassay procedure. Report on 21 cases. AB - The serological findings on 21 children with idiopathic autoimmune neutropenia are reported. A multiassay procedure was adopted including agglutination, immunofluorescence and cytotoxicity tests. Beside a cause-effect correlation between granulocyte antibodies and clinical course, a serologic polymorphism was found. As the sensitivity of each assay seemed to be related to the characteristics of the involved antigens and antibodies, as well as to the intrinsic sensitivity of the tests, the performance of a multiassay procedure appears to be advisable for the diagnosis and the follow-up of autoimmune neutropenia. PMID- 1413664 TI - Expression of red cell antigens C and c on neonatal and adult erythrocytes. A flow-cytometric analysis. AB - Red cell membrane proteins expressing Rh antigens appear to be important for the stabilization of the phospholipid membrane bilayer. Neonatal red cells possess a shorter in vivo life span and different deformability properties as compared to adult red blood cells, differences which could potentially be explained by different cell surface antigen densities of Rh-antigenic determinants. Although conventional serologic techniques have demonstrated Rh antigens on fetal and neonatal red cells, other more sensitive techniques are required when quantitative information is needed. Therefore, in this study, 40 adult and 45 neonatal red blood cell suspensions of differing Rh phenotypes were evaluated for C and c antigen density using flow cytometry. Neonatal and adult red blood cells had the same mean channel fluorescence intensity (expressed in mV) of c antigen in either the homozygous (cc) or heterozygous (cC) state: 485 +/- 44 versus 471 +/- 29 and 416 +/- 31 versus 411 +/- 23, respectively. In addition, neonatal and adult C antigen density was similar in heterozygous (Cc; 415 +/- 49 versus 455 +/ 44) and homozygous (CC; 438 +/- 53 versus 469 +/- 38 C states. As expected, homozygous (double dose) states for either C or c had greater intensities than heterozygous states for both neonates and adults. Although no differences were noted for C or c antigens, studies of other Rh antigens may indicate lower antigenic density in neonatal red cells. PMID- 1413665 TI - Point mutation in the glycophorin C gene results in the expression of the blood group antigen Dha. AB - The blood group Duch (Dha) antigen is located on glycophorin C (GPC). Total RNA prepared from the reticulocyte fraction of two Dh(a+) individuals were used in the synthesis of first-strand cDNA. The first-strand cDNA served as templates for the amplification of GPC-related DNA by polymerase chain reaction (PCR). The expected PCR product consisted of 412 base pairs. On sequencing the PCR-amplified DNA, a base change (cytosine----thymidine) at nucleotide 40 of the GPC cDNA was detected. Thus, the variant GPC (GPC.Dha) on Dh(a+) red cells has a substitution of leucine by phenylalanine at amino acid residue 14. PMID- 1413666 TI - Polynesian patients of the Gerbich-negative phenotype Ge: -2-3. PMID- 1413667 TI - Prevalence of bleeding as cause of death in HIV-seropositive patients with congenital clotting disorders. PMID- 1413668 TI - [The psychological preparation of patients with a paroxysmal systolic tachyarrhythmia for helium-neon laser treatment]. AB - The psychological structure was studied in 120 patients with paroxysmal disorders of the cardiac rhythm. Anxiety, obsessive-phobic, neurasthenic and ergopathic syndromes were singled out. It was established that psychological aspects of personality of the patients depended on the course of paroxysmal disorders of the rhythm and influence the number of arrhythmia triggering that often reduced the grade of medicosocial adaptation. Psychological preparation of these patients to laser treatment may be achieved by rational psychotherapy. Details of such psychotherapy are discussed. PMID- 1413669 TI - [A case of drug-induced litholysis of a uric acid staghorn calculus in the left kidney]. PMID- 1413670 TI - [The differential diagnosis of syringomyelia from pseudosyringomyelitic ulcero mutilating acropathy]. AB - The authors describe some differential diagnostic criteria of atypical syringomyelia and pseudosyringomyelitic acropathy. It was found that trophic disorders in the skin, metatarsal bones were in atypical syringomyelia usually associated with sensibility disorders of the dissociated type in the zone of corresponding segments. In pseudosyringomyelitic acropathy trophic and skin changes precede sensibility disorders and do not always correspond to innervation zones of the lower extremities. Dysraphic state is of importance for the diagnosis of syringomyelia. PMID- 1413671 TI - [My concept of hematopoiesis]. PMID- 1413673 TI - [Russian-Ukrainian medical dictionary. 7000 words]. PMID- 1413672 TI - [The methodological problems of conducting practical exercises in lecture series for physician advanced training in rheumatology]. PMID- 1413674 TI - [Autoimmune processes in patients with different forms of the clinical course of ischemic heart disease]. AB - A study of autoimmune processes in 286 patients with different clinical forms of ischemic heart disease revealed a high frequency of antibodies to "healthy myocardium" antigen in patients with non-stable stenocardia and acute myocardial infarction that may indicate acquirement of antigenic properties of the healthy myocardium. Patients with unstable stenocardia also show an increased antibody titer to vascular antigens that indicates the possible role of activation of autoimmune reactions in the mechanisms of destabilization of the clinical course of ischemic heart disease. PMID- 1413675 TI - [The content of ceruloplasmin, fibronectin and selenium in the blood of patients with an acute myocardial infarct]. AB - The content of ceruloplasmin, fibronectin and selenium was evaluated in the blood plasma of acute myocardial infarction patients within the first three days after onset if the disease. Results showed a reduction of fibronectin during the first hours after onset of the disease. The content of ceruloplasmin was increased, selenium reduced during the entire period of examination indicating pronounced disturbances of lipid peroxidation in the acute period of myocardial infarction as well as potentiation of antioxidant processes. PMID- 1413676 TI - [The action of the new beta-adrenoblocker Lopressor on the hemodynamics of hypertension patients]. AB - The authors carried out a complex clinico-instrumental investigation of the effect of a new cardioselective beta-blocking agent leprozor in 116 patients with hypertensive disease (stage II). A quantitative evaluation of the hemodynamics of the left compartments of the heart with two-dimensional echocardiography was carried out. Evaluation of the efficacy of using leprozor in this category of patients was based on an analysis of the state of their hemodynamics against the background of systematic intake of the drug for 7 months. Selection of the dosage was individual under the control of circulation parameters. It is concluded that leprozor proved effective in normalization of the hemodynamics in patients with hypertensive disease. PMID- 1413677 TI - [The effect of lunar rhythms on the incidence of acute coronary failure and hypertensive crisis]. PMID- 1413678 TI - [The indices of thrombocyte coagulating and fibrinolytic activity in rheumatoid arthritis patients]. AB - Blood coagulation values (thrombocyte count, adhesive-aggregation thrombocytic activity, coagulographic data) were analysed in 90 patients with rheumatoid arthritis (RA). Increase of plasma coagulation activity was observed in all coagulation activity grades. The anticoagulation activity was most pronounced in grade III RA activity. Thrombocytes of RA patients possessed procoagulant properties and lost significantly their fibrinolytic activity most expressed in grade II RA. This increased the thrombophilic tendency of the plasma potential creating favourable conditions for intravascular coagulation and microthrombus formation, resulting in deterioration of the rheological properties of the blood and the course of the rheumatoid synovitis. PMID- 1413679 TI - [The use of thermographic and immunological indices in choosing adequate treatment for patients with rheumatoid arthritis and arthrosis deformans]. AB - A study is presented of the thermal semeiotics and the state of cellular and humoral immunity in 29 patients with osteoarthrosis deformans, 35 patients with rheumatoid arthritis of different activity. It is recommended to use data of the thermographic picture and immunological status for objectivation of the character of the pathological process, differential diagnosis and dynamic express evaluation of treatment adequacy. PMID- 1413680 TI - [The importance of osteoscintigraphy for the early detection of rheumatic joint lesions]. AB - The scintigraphic semeiotics was investigated of involvement of osteoarticular system in rheumatoid polyarthritis in 186 patients (79 of them suffered of rheumatoid arthritis, 62 of systemic lupus erythematosus, 34 of systemic scleroderma, 11 of dermatomyositis). Roentgenological examination was supplemented by consecutive local scintigraphy of axial skeleton and peripheral joint by of gamma rays with labeled 99mTc phosphate complexes. Isoactive zones with subsequent quantitative evaluation of the information were obtained as a result of computerized processing of the scintigraphic images of the joints. The results were compared with those obtained in patients with rheumatoid arthritis. It was established that inspite of the similarity of the scintigraphic manifestations, each of them has its regularities due to differences of the pathomorphological processes in the joints. PMID- 1413681 TI - [The efficacy of treating glomerulonephritis patients with a hematuria component]. AB - A clinical evaluation was carried out of treatment efficacy of patients suffering of glomerulonephritis with hematuria component. TREATMENT: membrane stabilizing therapy including unithiol, dimephosphon (delagil) and alpha-tocopherol acetate. Duration of this treatment was 1 month; 2 months--with alpha-tocopherol and delagil; 6 months--with delagil. TREATMENT was carried out in 80 patients. Six month follow-up was evaluated in 62 patients. In 48 patients the treatment was effective as concerns proteinuria and in 4--only hematuria. Comparing the results of such treatment with indomethacin treatment where a positive dynamics was observed in 10 of 38 patients and only in 2 patients improvement concerned proteinuria and erythrocyturia. CONCLUSION: membrane stabilizing therapy is the method of choice in comparison with traditional indomethacin treatment. PMID- 1413682 TI - [The role of immune links in the gastric acid-forming function in peptic ulcer patients]. AB - Results are of a comparative analysis of immunological and biochemical parameters in 116 patients with duodenal ulcer before operative treatment and in the follow up (1-3 years) after different types of vagotomy. A close relationship has been established between the immune and neurohumoral links of regulation and state of the acid forming gastric function in patients with ulcer disease. PMID- 1413683 TI - [The clinico-morphological characteristics of malignant non-Hodgkin's lymphomas]. AB - It was established that most patients with non-Hodgkin malignant lymphomas against the background of secondary immunodeficiency show an activation of the saprophytic bacterial and mycotic flora that results in the development of different infectious complications essentially, thus, influencing the course and prognosis of the disease. A dependence was established between the malignancy grade of non-Hodgkins lymphomas and frequency of development of non-infectious complications. PMID- 1413684 TI - [Changes in the cytochemical indices and in the phagocytic activity of the leukocytes during the combined therapy of rectal cancer]. AB - Changes of cytochemical indices and phagocytic activity of neutrophil granulocytes of the peripheral blood were revealed in patients with cancer of the rectum at different stages of combined treatment. These changes evidence an increase of vascular permeability and catabolism, disorders of energy resources, oxidation-reduction processes and functional activity of granulocytes. The dynamics of changes of cytochemical indices of leucocytes reflect the efficacy of different methods of treatment and prophylaxis of postoperative purulent complications. PMID- 1413685 TI - [The electrical excitability of the mimetic muscles in patients with a facial nerve lesion]. AB - Sixty patients with lesions of the facial nerve were examined. Electroexcitability of the mimic muscles was determined. The obtained data allow to predict the state of the function of mimic muscles and institute adequate electrostimulating therapy of corresponding intensity and duration. PMID- 1413686 TI - [The enzymatic activity of ammonia metabolism in the liver during the parenteral nitrogen feeding of animals with experimental liver failure]. AB - It was established that liver insufficiency the activity of hepatic glutamate dehydrogenase is markedly reduced that is, apparently, the main cause of hyperammonemia that accompanies hepatic encephalopathy. Here occurs a significant reduction of the processes of ammonia detoxication with formation of glutamine in the liver as evidenced by changes of the activity of glutamine synthetase. Administration parenterally of a preparation of nitrous feeding increases essentially ammonia detoxicating function of muscular tissue which supplements the detoxicating function of the liver. PMID- 1413687 TI - [The role of autoimmune reactions in the development of disseminated sclerosis]. AB - The immune status was investigated in 97 patients with multiple sclerosis. Patients of this group showed marked changes at the cellular lever of the immune system. T-lymphocytopenia was accompanied by a dysbalance of the main correlative cells according to a relatively hyposuppressor variant of immune deficit with formation of circulating immune complexes and thermodependent lymphocytotoxic autoantibodies. PMID- 1413688 TI - [Mineral metabolism in bacterial meningoencephalitis]. AB - The authors investigated the concentration of some metals in the cerebrospinal fluid in 70 patients with bacterial meningoencephalitis in the dynamics of the inflammatory process and in different regions of the brain in 10 autopsy cases. There was a correlation between potassium, sodium, manganese, magnesium, copper and zinc in the brain and quantity of water, as well as their concentration in cerebrospinal fluid. It is shown that determination of some metals in the cerebrospinal fluid allows to diagnose edema swelling of the brain and to predict the disease sequels. PMID- 1413689 TI - [The characteristics of the instrumental diagnosis of organic diseases of the hepatopancreatoduodenal area in patients with the postcholecystectomy syndrome (a review of the literature)]. PMID- 1413690 TI - [Immunodeficiency states in lung diseases and the possible ways for their correction]. AB - The author discusses problems on the mechanisms of formation of immunodeficiency state in pulmonary diseases. It is suggested that T-cell deficit revealed in pulmonary pathology is caused by several factors (intoxication, mediators of allergic-reactions immune complexes, C-reactive protein, hormones, endorphin-like substances etc.), the removal of which furthers normalization of the immune system. Data are reported on the possible variants of secondary immunodeficiency states and the main regularities for immunocorrection are discussed. PMID- 1413691 TI - [A program for the accelerated activation of myocardial infarct patients and its implementation in the hospitals and sanatoria of Ukraine]. AB - The possibility is shown of reducing the time of hospitalization for 7-12 days in 25% of patients with a history of myocardial infarction. An analysis of health resort rehabilitation of patients according to program of enhanced activation revealed that such rehabilitation program proved effective and showed the possibility of its realization in conditions of practical medicine. PMID- 1413692 TI - [The prognostic significance of heart rhythm and conduction disorders in the postinfarct period]. PMID- 1413693 TI - [The prevalence of ischemic heart disease and its relation to the incidence of blood rheological disorders]. PMID- 1413694 TI - [Sex hormones and cerebral hemodynamics in men with cerebrovascular insufficiency]. AB - The authors determined content of steroid hormones (testosterone, estradiol) and gonadotropic pituitary hormones (follicle stimulating, luteinizing, prolactin) in blood plasma by means of radioimmunological assay and evaluated the state of cerebral hemodynamics by results of zonal rheoencephalography in 77 patients with initial manifestation of circulatory brain insufficiency, transient disorders of the cerebral circulation and in the restorative period of stroke against the background of cerebral atherosclerosis. Established was a significant correlation between the content steroid sex hormones and the main quantitative values of the rheoencephalograms of the above patients. PMID- 1413695 TI - [The use of acoustic vibromassage in diseases of the respiratory organs]. PMID- 1413696 TI - [The fibrinolytic system of bronchial asthma patients in the late terms of pregnancy]. AB - Women suffering of infectious-dependent bronchial asthma show at the second half of pregnancy a sharp reduction of the fibrinolytic potential that is manifested in a decrease of plasminogen activator and urokinase activity of the urine, in an elevation of the antiactivator and antiplasmin activity, growth of the concentration of alpha2-macroglobulins. At the same time high levels of fibrinogen are noted and low levels of fibrin degradation. PMID- 1413697 TI - [The pathophysiological characteristics of anaphylactic shock]. AB - Data are reported on the course of anaphylactic shock in 27 patients. It was established that respiratory insufficiency is as a rule, a sequel of distress syndrome. The symptoms of hepatic failure are mainly manifested in patients with a previously involved liver. Hyperazotemia has a productive character. PMID- 1413698 TI - [The incidence of urolithiasis (based on autopsy data from the Donetsk Province Clinical Hospital)]. AB - Autopsy data indicate that urolithiasis is found in 3.6% of 100 autopsies, most frequently in men (62 cases) over 40 years of age. In 2/3 of patients the length of the disease was under 8 years, rarer over 15 years. In most cases renal involvement was bilateral (72 patients). In more that 70% two or three operations were performed. A pathogenetic relationship was found between urolithiasis and malformations of the kidneys and ureters, urinary stasis in disorders of innervation of lesser pelvis organs, hyperplasia of the prostate and disorders of the mineral metabolism. PMID- 1413699 TI - [The evaluation of the efficacy of repeated inoculations against influenza using inactivated vaccines]. PMID- 1413700 TI - [Transcutaneous muscle electrostimulation and therapeutic physical exercise in the rehabilitation of patients with the pain syndrome in osteochondrosis of the lumbar spine]. PMID- 1413701 TI - [Senescent-hypochondriac disorders accompanied by subjective signs of involvement of the genitalia]. AB - Examined were 65 patients complaining of unpleasant sensations in the zone of sex organs. It was established that neither the localization of hypochondriac feelings, the character of senestopathias nor their characteristic aspects of interpretation and emotional accompaniment are not of significance for differential diagnosis with neuroses and torpid schizophrenia. The diagnosis should be based on the presence or absence of characteristic for schizophrenia personality changes, thinking disorders. PMID- 1413702 TI - [The efficacy of different regimens for using millimeter-wave resonance therapy in duodenal peptic ulcer]. PMID- 1413703 TI - [A trial of the clinical use of millimeter-wave resonance therapy with different levels of electromagnetic radiation intensity]. PMID- 1413704 TI - [Phytotherapy in the combined treatment of autonomic vascular disorders in workers of industrial enterprises]. PMID- 1413705 TI - [A case of hyperergic vasculitis]. PMID- 1413706 TI - [A case of bettolepsy in acute pneumonia]. AB - Literature lists more than 300 case reports of bettolepsy developing mainly in chronic diseases of the respiratory organs (chronic bronchitis, bronchial asthma, pulmonary emphysema, cor pulmonale) as well as in patients with epilepsy and organic brain diseases. The authors describe a case of bettolepsy in a patient with acute (croupous) pneumonia without respiratory diseases in the anamnesis and without a burdened neurological status. The role of nicotin and alcohol in the development of bettolepsy is shown. The problems of pathogenesis, clinical picture, differential diagnosis and treatment of bettolepsy are discussed. PMID- 1413707 TI - [The use of the vif gene expression product of HIV-1 in bacteria for detecting specific antibodies in the sera of infected persons]. AB - A fragment of the genome of human immunodeficiency virus type 1 (HIV-1) coding for p23 protein, the product of vif gene, was cloned in a plasmid vector pUR291. The resulting recombinant plasmid pLacVif1 was conducive in E. coli cells to the synthesis of a hybrid polypeptide with molecular weight of 136 kDa containing antigenic determinants of p23 protein of HIV-1. The employment of this polypeptide for analysis of HIV-1-positive sera by indirect enzyme immunoassay showed that vif-specific antibodies were found in 53% of the cases and their appearance was not related to the stage of the disease. PMID- 1413708 TI - [The antigenic and immunogenic properties of a recombinant protein of the HIV-1 gag-pol gene secreted by Saccharomyces cerevisiae yeast cells]. AB - Analysis of the immunological properties of recombinant proteins of HIV-1 gene gag-pol secreted by yeast cells S. cerevisiae was carried out. The proteins under study interacted with antibodies from HIV-1-seropositive human subjects and with antibodies of rabbit immune serum to the native virus as effectively and specifically as natural HIV-1 proteins. The yeast gag-pol-protein complex was markedly immunogenic and induced in animals synthesis of antibodies of a certain specificity spectrum. A comparative immunochemical analysis of the properties of the recombinant proteins carried out by EIA and immune blot showed a certain degree of similarity between the yeast proteins and those of analogous construction produced in E. coli system. PMID- 1413709 TI - [The isolation of HIV from children with the initial signs of an HIV infection and from symptom-free carriers]. AB - A high rate of HIV carrier state was observed in seropositive children with early symptoms of HIV infection. The virus was also isolated from 2 seropositive adults (mothers) showing no clinical manifestations. The intervals of virus manifestation in culture varied from 6 to 30 days with maximal frequency of detection in the 2nd week. Different modifications of the procedure for HIV isolation were assayed, and it was shown that the efficacy of isolation (shortening of the period of virus detectability and increase in the number of the antigen-containing cells) could be improved by the addition to the culture of the Jurkat-tat III line expressing the product of the tat gene important for virus reproduction. PMID- 1413710 TI - [The reproduction of reassortant influenza A and B viruses with a known genome composition in different cell systems]. AB - Reproduction of parental strains and reassortants (with known genome composition) of influenza A and B viruses was studied in chick embryos (CE) and in different cell lines (SPEV, MDCK, BHK-21, M22, etc.). The results agree with the concept that the yield of influenza A virus in CE depends on its M-gene. At the same time, the experimental results suggest that reproduction of influenza B virus in the same system is not determined by M-gene. Reproduction (hr-phenotype) of influenza A and B viruses in cell cultures was shown to be determined not only by the gene coding for hemagglutinin but also by other virus genes, the reproduction level being dependent on different genes in different cell systems. PMID- 1413711 TI - [The evaluation of the degree of attenuation of cold-adapted influenza A virus strains in CBA-strain mouse and Syrian hamster models]. AB - The pattern of the infectious process induced by the epidemic A/Leningrad/134/57 (H2N2) virus and its cold-adapted (CA) variants in CBA mice and Syrian hamsters was studied. The strains under study inoculated into the animals under a mild ether anesthesia differed by virulence, reproductive capacity in the nasopharynx, trachea and lungs, as well as by the isolation rate from extrarespiratory organs of both mice and hamsters. Upon intranasal inoculation of mice without anesthesia, the CA strains were found to be incapable of dissemination into the lower parts of the respiratory tract with distinguished these viruses from the original epidemic strain A/Leningrad/134/57 as well as from the mouse-adapted strain A/PR/8/34 (H1N1) used as control. The experimental results show that both models are suitable for laboratory evaluation of the attenuation degree of human influenza viruses. PMID- 1413712 TI - [The antigens and nucleotide sequences of influenza A and B viruses in the lymphocytes of human peripheral blood]. AB - Markers of influenza A and B viruses (antigens of hemagglutinin and specific nucleotide sequences) were detected in lymphocyte preparations from normal subjects. The rate of detection of the antigens and specificity (type and subtype appurtenance) of the markers correlated with the influenza epidemic situation. Lower titers of antibodies to the virus whose antigens were present in lymphocytes were observed. PMID- 1413713 TI - [The antigenic characteristics of the influenza virus subpopulations isolated from a single patient]. AB - Examinations by HI and EIA of influenza A (H3N2) virus isolates of 1985-1990 showed the strains derived from nasopharyngeal washings from patients to present very frequently as phenotypic mixtures of stable virus variants. Immunological analysis with monospecific antibody to hemagglutinin antigenic sites revealed a wide spectrum of antigenic activity based on the degree of relationship with viruses of previous years. By means of the immune pressing with antibody of different specificity the isolated strains could be divided into 2 subpopulations each characterized by the presence of only three antigenic sites. The subpopulations homogeneous by the antigenic composition of hemagglutinin represented the strains with antigenic markers of hemagglutinins of previous variants with drift variants of epidemic nature. PMID- 1413714 TI - [The reproductive characteristics of the tick-borne encephalitis virus in interspecific somatic hybrids]. AB - The study dealt with features of tick-borne encephalitis virus reproduction in two series of interspecies somatic hybrids generated by fusion of transformed cells of Chinese hamster (Ag17) with human diploid fibroblasts (KM/3) and with pseudonormal cells of Indian deer (Muntiacus munjak) (KOM). The viral infection in hybrid Ag17 cells ran an acute course with cell damage, but in KM/3 and KOM cells virus multiplication was not accompanied by the development of cytopathic effect. Two other parameters of tick-borne encephalitis virus infection under study: the extent of infectious particles production and electroimmunochemical properties were found to be under control of genomes of different parental cells. PMID- 1413715 TI - [The immunogenic properties of Marburg virus proteins]. AB - Immunogenic and protective properties of VP40 and NP proteins of Marburg virus were studied. VP40 protein was shown to have insignificant immunogenicity and NP protein to be capable of protecting the animals from lethal infection by stimulation of cell-mediated immunity. No significant increase in the specific antibody level was found. PMID- 1413716 TI - [On the centenary of the discovery of viruses]. PMID- 1413717 TI - [The antiproliferative activity of monoclonal anti-idiotypic antibodies imitating the biological effects of human alpha-interferons]. AB - The experimental data from the study of antiproliferative activity (AP-activity) of monoclonal antiidiotypic antibody (mono-Ai-At) imitating biological effects of human alpha interferons (h-IF-alpha) are presented. The mono-Ai-At present in the ascitic and culture fluids (the culture fluid was obtained from cultivation of hybrid cells immobilized in alginate-gelatine gel) were shown to inhibit propagation of IF-sensitive continuous cells from normal and tumor tissues. The AP-activity of mono-Ai-At was found to be within the range of their antiviral activity. It is concluded that mono-Ai-At may be used as a new experimental model for investigation of h-IF-alpha biological effects. PMID- 1413718 TI - [The isolation and identification of the Sindbis virus from migratory birds in Estonia]. AB - The data on isolation from birds and identification of two strains of alphaviruses in Estonia in the territory of Vilsandy natural reserve are presented. Electron microscopy of purified virions allowed the isolates to be classified into the family of togaviruses, and serological identification (neutralization test, CFT) using polyvalent sera and monoclonal antibody showed them to belong to Sindbis virus. PMID- 1413719 TI - [Carriage of the hepatitis B virus surface antigen as one of the unfavorable prognostic factors in breast cancer]. PMID- 1413720 TI - Are malpractice claims driving up the cost of health care? Don't be fooled. PMID- 1413721 TI - Ask the nurse attorney. To report or not to report--that is the question. PMID- 1413722 TI - What to do when you believe staffing is unsafe. Part 2: Nursing practice committees. PMID- 1413723 TI - The role of the ethical decision-making process in health care reform. WSNA Health Access Task Force Report #10. PMID- 1413724 TI - What to do when you believe staffing is unsafe. Part 3: New WSNA publication helps nurses deal with unsafe staffing. PMID- 1413725 TI - Our health care crisis is not new but different today. WSNA Health Access Task Force Report #11. PMID- 1413726 TI - WSNA BSN/certification survey: baccalaureate for certification? PMID- 1413727 TI - Ask the nurse attorney. Co-signing others' charting. PMID- 1413728 TI - Pensions and savings retirement plans. PMID- 1413729 TI - Making research work for you. PMID- 1413730 TI - Reflections in Thailand. PMID- 1413731 TI - Agency RNs enjoy independent contractor relationship. PMID- 1413732 TI - An interview with Margarethe Cammermeyer. Interview by Claudette Boudreaux. PMID- 1413733 TI - [Biotransformation of zearalenone]. AB - The conversion of Zearalenone by some strains of microorganisms was investigated. When the selective strains of Rhodotorula sp., Arthrobacter sp., Saccharomyces sp., and Candida sp. were incubated by shaking or standing at 28 degrees C for 72 h with an alcoholic solution of Zearalenone as the substrate at a concentration of 2-10 mg/ml ethanol (50-100 micrograms/ml medium), it was readily converted to give Zearalenols, consisting either mainly of the alpha-isomer (e.g. 96% in case of Rhodotorula sp. and 84% in case of Arthrobacter sp. as determined by HPLC) or beta-isomer (e.g. 91% and 92% in Saccharomyces sp. and Candida sp., respectively). The structure of the product was confirmed by 13C-NMR, MS and HPLC. PMID- 1413734 TI - [Microbiological production of 3-oxo-bisnorchola-1, 4-dien-22-oic acid from cholesterol by an Arthrobacter 82]. AB - Among nineteen strains of Arthrobacter which showed to be able to decompose cholesterol in preliminary experiments, a strain of Arthrobacter 82 was selected for microbiological production of 3-oxo-bisnorchola-1,4-dien-22-oic-acid (BNC) from cholesterol. The yield is over of 50% weight percent concentration of 0.25% in the presence of cobalt sulfate. The main intermediate in such a conversion process is cholestenone. Lower glucose and higher corn steep liquor concentration were favorable for side chain degradation of cholestenone and more BNC could be produced. BNC was crystallized in acidic solution and obtained by centrifugation. The structure and characteristics of BNC has been identified by means of conventional physical, chemical and spectrometric techniques. PMID- 1413735 TI - [Purification and characterization of alpha-glucosidase from an extreme thermophile, Thermus thermophilus HB 8]. AB - A highly thermostable alpha-glucosidase (E C.3.2.1.20) from an extreme thermophile, Thermus thermophilus HB 8, was purified to homogeneous by ammonium sulfate fractionation, DEAE-cellulose chromatography and preparative slab gel electrophoresis. The enzyme was purified 17 fold with 21% recovery of activity. The enzyme had a molecular weight of 67000 by SDS-PAGE. The isoelectric point was pH4.5 by IEF on PAG. The enzyme hydrolized p-nitrophenyl-alpha-glucoside (PN-PG), sucrose and maltose, but not cellobiose, melibiose and soluble starch. The km value for PNPG was 0.4mmol/L, the Vmax was 0.29 mumol.min-1.mg-1. The enzyme exhibited high thermostability. After incubation at 90 degrees C for 10 h in 50 mmol/L acetate buffer pH 5.8, the enzyme retained 90% of its original activity. The half-live (t1/2) at 95 degrees C was 108 min. The enzyme was activated by Mg2+, Mn2+, Ca2+, Ba2+ and strongly inhibited by Hg2+, Cu2+. Modification of the enzyme by EDC or DEPC led to complete loss of activity, which suggests that carboxyl group(s) and histidine residue(s) are essential for activity of alpha glucosidase. PMID- 1413736 TI - [An urease negative Cryptococcus neoformans]. AB - We report an urease negative Cryptococcus neoformans derived from pigeon dropping. This isolate produced brown pigmented colonies on cornmeal Tween-80 agar with 300 micrograms/ml caffeic acid, but was failure to hydrolyze urea. More identification tests were performed for this isolate, such as assimilation and fermentation of carbohydrates, nitrate assimilation, production of starch like compound, growth on GCP medium, germ tube formation and inoculation of mice, ect. Most of the results showed that the microbiological characteristics of the isolate were typical of C. neoformans except for negative urease test. Even though there has been a report about an urease negative C. neoformans derived from an AIDS patient, but we have never found any report about isolation from pigeon dropping or nature environment. We should pay attention to the exist of this atypical strain of C. neoformans in nature environment and the possibility of infection to human being. Additionally, we also be aware of the possibility of neglect when this urease negative C. neoformans is identified with urease test. PMID- 1413737 TI - [Study and preparation of Vi-PHA reagent and its application for detection of Salmonella typhi carriers]. AB - Purified S. typhi Vi antigen is sensitized with equal volume of tannic acid treated formalational sheep erythrocytes (SRBC) at a final concentration of 1 microgram/ml. The Vi-passive hemagglutination assay (Vi-PHA) diagnostic reagent is developed to detect Vi antibodies to S. typhi for the detection of chronic carriers after typhoid fever and the screening S. typhi healthy carriers from food-handlers, which is characterized with high sensitivity, strong specificity and good stability. This Vi-PHA reagent is able to detect 1.16 micrograms/ml of Vi antibodies and doesn't make any cross reaction with healthy sera. For the sera of other diseases, the cross rate is only 0.84%. Using this reagent, 19 positive sera (6.93%) are detected from 274 convalescent sera from typhoid fever, 14 convalescents of which are stool-culture S. typhi positive, that persists a positive rate of 73.68%; 3 positive sera are detected from 106 foodhandlers, one of which is stool-culture S. typhi positive. Therefore, the reagent is simple, convenient, rapid and easy to be applicated in basic unit. PMID- 1413738 TI - [Expression and secretion of alpha-amylase gene from Bacillus subtilis in E. coli]. AB - The E. coli which carrying the alpha-amylase gene fragment cloned from B. subtilis secreted the gene products into the medium. The reason is the exogenous gene fragment act on the cell wall of E. coli by some way, gives rise to the change of its structure. It leads up to the alpha-amylase and some periplasm proteins passing through the cell wall into the medium. It also causes the change of host colonial morphology. The secrete process are non-specific. PMID- 1413739 TI - Dexamethasone and bacterial meningitis. A meta-analysis of randomized controlled trials. AB - A meta-analysis of 5 randomized, controlled trials using dexamethasone as adjunctive therapy in the treatment of bacterial meningitis in children was done to assess the efficacy in reducing sequelae. A 6th study including both children and adults was analyzed separately. Results of the 5 pediatric studies indicated no significant difference in case-fatality rate between the placebo and dexamethasone groups. Significantly more neurologic sequelae were found in the placebo group during the period from discharge from hospital to 6 weeks after discharge (relative risk [RR] = 1.99, 95% confidence interval [CI] 1.13 to 3.53) and during the period beginning 6 months after discharge (RR = 3.90, 95% CI 1.72 to 8.85). The incidence of neurologic sequelae from 6 weeks to 6 months after discharge, though less with dexamethasone administration, did not reach statistical significance. The frequency of bilateral hearing loss was significantly greater in the placebo group (RR = 4.12, 95% CI 1.74 to 9.79), but unilateral loss was not statistically different in the two groups. Dexamethasone administration in addition to antimicrobial therapy appears to be effective in reducing neurologic sequelae and bilateral hearing loss associated with bacterial meningitis in children. PMID- 1413740 TI - Risk for AIDS in multiethnic neighborhoods in San Francisco, California. The population-based AMEN Study. AB - To examine the actual and potential spread of human immunodeficiency virus (HIV) from an acquired immunodeficiency syndrome (AIDS) epicenter to surrounding neighborhoods, we studied the prevalence of the viral infection and AIDS risk behaviors from 1988 to 1989 in a representative sample of unmarried whites, African Americans, and Hispanics living in San Francisco. We surveyed 1,770 single men and women aged 20 to 44 years (a 64% response rate) in a random household sample drawn from 3 neighborhoods of varying geographic and cultural proximity to the Castro District where the San Francisco epidemic began. Of 1,369 with blood tests, 69 (5%) had HIV antibodies; all but 5 of these reported either homosexual activity (32% HIV-positive; 95% confidence interval [CI] = 23%, 41%), injection drug use (5% HIV-positive; CI = 1%, 14%), or both (59% HIV-positive; CI 42%, 74%). Homosexual activity was more common among white men than among African American or Hispanic men, but the proportion of those infected was similar in the 3 races. Both the prevalence of homosexually active men and the proportion infected were much lower in the 2 more outlying neighborhoods. Risk behaviors in the past year for acquiring HIV heterosexually--sex with an HIV-infected person or homosexually active man or injection drug user, unprotected sexual intercourse with more than 4 partners, and (as a proxy) having a sexually transmitted disease -were assessed in 1,573 neighborhood residents who were themselves neither homosexually active men nor injection drug users. The prevalence of reporting at least 1 of these risk behaviors was 12% overall, and race-gender estimates ranged from 5% among Hispanic women to 21% among white women. We conclude that in San Francisco, infection with HIV is rare among people who are neither homosexually active nor injection drug users, but the potential for the use spread of infection is substantial, as 12% of this group reported important risk behaviors for acquiring the virus heterosexually. PMID- 1413741 TI - Health care use by human immunodeficiency virus-infected students at a California student health service. AB - We report characteristics of 16 college students with human immunodeficiency virus (HIV) infection but without the acquired immunodeficiency syndrome who received care at a student health center at a major university in California. Sociodemographic and clinical data and medical expenditures were obtained retrospectively from medical charts and computerized billing records. All 16 students were men who had sex with men, and 3 had also used intravenous drugs. Dermatologic conditions, upper respiratory tract infections, gastrointestinal conditions, anemia, lymphadenopathy, sexually transmitted diseases, and ophthalmologic conditions were more frequent among HIV-infected students than among the general student population using the health center. On average, HIV infected students visited the student health service about 3 times more often and incurred charges about 10 times higher than the general population of students visiting the health center. Student health centers, which have been at the forefront of developing strategies for HIV prevention, education, and counseling, must also develop treatment programs for HIV-infected students. PMID- 1413742 TI - Factors influencing family physicians to continue providing obstetric care. AB - To determine the reasons some family physicians continue to practice obstetrics when most of their colleagues do not, we surveyed family physicians in 26 counties of northern California whose practices include obstetrics and those who have recently discontinued it. In all, 70% of family physicians practicing obstetrics cited enjoying it as a reason for continuing this practice. Over a third of family physicians practicing obstetrics thought that obstetric practice was a responsibility to the community. Only 1 in 6 reported obstetrics to be important in terms of financial implications. Despite this, family physicians practicing obstetrics had a mean gross income derived from obstetric practice of $30,000 above the cost of their total malpractice premium. In contrast, a comparison group of family physicians who had recently discontinued obstetrics cited malpractice insurance costs most frequently as the reason for discontinuing it. Nearly 40% of these physicians indicated that they would be willing to return to obstetrics if circumstances were to change substantially. The most frequently cited change necessary for these physicians to return to obstetrics was a reduction in malpractice insurance rates. PMID- 1413745 TI - Use of thallium 201 in tumor evaluation. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in nuclear medicine. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in nuclear medicine that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Nuclear Medicine of the California Medical Association, and summaries were prepared under its direction. PMID- 1413746 TI - Technetium 99m-hexamethyl propyleneamine oxime-labeled leukocytes for diagnosis of infection. PMID- 1413747 TI - Radionuclide evaluation of brain death. PMID- 1413744 TI - Do we need an intravenous fluoroquinolone? AB - Intravenous ciprofloxacin, the first parenteral fluoroquinolone available in this country, represents another class of antimicrobial agents from which physicians must choose when treating nosocomial infections. Fluoroquinolones are bactericidal antimicrobial agents that act by inhibiting DNA gyrase. They are active in vitro against most gram-negative bacteria and methicillin-susceptible staphylococci. Activity against anaerobic bacteria and streptococci is poor. The rapid development of bacterial resistance in centers with high quinolone usage is of great concern. Resistance develops most commonly in Pseudomonas aeruginosa and staphylococci. Resistance emerges most often when quinolones are used to treat chronic infections or in patients with poorly drained abscesses, necrotic tissue, or indwelling catheters. Clinical trials have shown ciprofloxacin to be as effective as ceftazidime in the treatment of infections caused by gram-negative bacteria. Although the overall frequency of side effects to fluoroquinolones is low, seizures and allergic reactions have been attributed to their use. Ciprofloxacin inhibits the metabolism of theophylline, and morbidity and death have been reported in patients taking the two drugs concomitantly. Parenteral fluoroquinolones should be reserved for the treatment of gram-negative bacterial infections in patients in whom standard agents cannot be used. PMID- 1413748 TI - Radionuclide therapy for thyroid disease. PMID- 1413743 TI - Endoscopic laser therapy in gastroenterology. AB - Endoscopic laser therapy has become an important and widely used tool in gastroenterology. It has become important for outpatient palliative therapy for ablating obstructing gastrointestinal neoplasms. This method has often circumvented the need for major palliative surgical resections. Caution must be applied to laser therapy for potentially curable malignant neoplasms because, with vaporization of the target tissue, no tissue specimen is available to assure that local or invasive residual carcinoma is excluded. Therefore, in good surgical candidates, surgical resection of potentially curable cancers is always recommended. In the future, however, the combination of refined endoscopic ultrasonography and laser fluorescence techniques may lead to earlier detection, more precise localization, and even curative ablation of gastrointestinal malignancy. PMID- 1413749 TI - Diagnostic and therapeutic uses of metaiodobenzylguanidine. PMID- 1413750 TI - Chronic atypical seizure disorder and cataracts due to delayed diagnosis of pseudohypoparathyroidism. PMID- 1413751 TI - Hypokalemia as a cause of tetany. PMID- 1413752 TI - Current management of diabetic retinopathy. AB - Diabetic retinopathy progresses through three distinct stages. A rational approach to management is based on an understanding of the pathophysiology of each stage. Based on the results of national multicentered clinical trials of laser photocoagulation and other treatments, advances in our understanding of the pathogenesis and treatment can now make a dramatic impact on blindness in the diabetic population: Panretinal laser photocoagulation treatment can reduce the risk of vision loss from high-risk proliferative diabetic retinopathy by at least 50%. Laser photocoagulation treatment of clinically significant diabetic macular edema can reduce the risk of vision loss by more than 50%. Vitrectomy can restore useful vision to some patients with severe diabetic retinopathy and vitreous hemorrhage with or without an accompanying traction retinal detachment. Diabetes 2000 is a new project sponsored by the American Academy of Ophthalmology, the goal of which is to eliminate preventable blindness from diabetes by the year 2000. As its name implies, Diabetes 2000 will be a long-term project aimed at a specific disease--diabetic retinopathy and its complications. It will provide the latest research findings to ophthalmologists and primary care physicians as the first priority, followed by the education of patients and the general public. Recent advances and treatment guidelines for the medical and surgical treatment of diabetic eye disease will be emphasized through the continuing education of ophthalmologists, other physicians, and allied health professionals. In later phases, educational programs for diabetic persons and the public will be developed. Ultimately, improved access of diabetic patients to ophthalmologic care and a close working relationship between ophthalmologists and primary care physicians will ensure early detection of diabetic retinopathy and the timely delivery of state-of-the-art treatments. PMID- 1413753 TI - Global health leadership. A continuing US challenge. PMID- 1413754 TI - Scientific medicine, social ills, and child health. PMID- 1413755 TI - Playing the cost-containment game. PMID- 1413756 TI - Earthquakes and the office-based surgeon. AB - A major earthquake may strike while a surgeon is performing an operation in an office surgical facility. A sudden major fault disruption will lead to thousands of casualties and widespread destruction. Surgeons who operate in offices can help lessen havoc by careful preparation. These plans should coordinate with other disaster plans for effective triage, evacuation, and the treatment of casualties. PMID- 1413757 TI - You light up my life ... and liver. Gastroenterologic laser therapy in the 1990s. PMID- 1413758 TI - Eight years and counting--what can Americans do? PMID- 1413760 TI - History and diagnosis. PMID- 1413759 TI - Meta-analysis redux-steroids and meningitis revisited. PMID- 1413761 TI - History and diagnosis. PMID- 1413762 TI - If syncope, think long QT. PMID- 1413763 TI - Cross-cultural medicine. PMID- 1413764 TI - Cultural diversity--changing the context of medical practice. PMID- 1413765 TI - Translation is not enough. Interpreting in a medical setting. AB - Unique obstacles must be overcome when providing medical care to patients who have an incomplete command of the English language. Serious barriers to effective communication may arise at the exact point where our health care system must succeed or fail. Miscommunication, differences in attitudes about health care, and various other misunderstandings interfere with or frustrate good health care for these patients and their families. Such difficulties are best overcome by the use of a professional interpreter who can ensure good communication between patients and health care professionals. My daily experiences as a professional medical interpreter and translator in Spanish provide insights into the complexities of bilingual and bicultural communication in the hospital setting. Although the examples given relate to Hispanic patients, the lessons learned can be extended to other foreign language patients as well. PMID- 1413766 TI - Modesty, sexuality, and breast health in Chinese-American women. AB - Although breast cancer rates among Chinese women are lower than among white women, breast cancers and other breast diseases often go undetected and untreated in Chinese women. Cultural values with respect to modesty and sexuality, especially in unmarried women, partly account for a Chinese lack of attention to breast health. In addition, institutional barriers, such as an unavailability of information in Chinese languages, few female physicians, and an absence of educational campaigns, contribute to Chinese women's neglect of breast health. PMID- 1413767 TI - Health, illness, and immigration. East Indians in the United States. AB - East Indian immigrants to the United States represent the diversity in religion, language, and culture that exists in India, so it is difficult to make unequivocal statements about their health beliefs and behaviors. Despite the diversity, an understanding of Ayurvedic humoral concepts of health and illness provides a key to some pervasive and persistent ideas and practices. India has a pluralistic medical system in which Western medicine, which is increasingly popular for some ailments, is one option among many. Even those who are familiar with the "Western" medical system in India may find American medicine alien. PMID- 1413768 TI - Health issues of Afghan refugees in California. AB - Since the 1979 Soviet invasion of Afghanistan, more than 6 million Afghan refugees have become the world's largest refugee population. Although refugees in Pakistan and Iran are now beginning to repatriate, continuing political turmoil in Afghanistan and children's acculturation and educational opportunities will keep many Afghans in the United States permanently. Although there are no accurate statistics, local resettlement agencies and Afghan community leaders estimate that there are 10,000 to 35,000 Afghans in northern California. They suffer from a variety of problems common to refugees: language, economic and occupational problems, and substantial challenges in psychological, family, social, and cultural adjustment to the United States. Although many Afghans are doing well, many others have depression, psychosomatic symptoms, and posttraumatic stress disorder. PMID- 1413769 TI - Gypsies and health care. AB - Gypsies in the United States are not a healthy group. They have a high incidence of heart disease, diabetes mellitus, and hypertension. When they seek medical care, Gypsies often come into conflict with medical personnel who find their behavior confusing, demanding, and chaotic. For their part, Gypsies are often suspicious of non-Gypsy people and institutions, viewing them as a source of disease and uncleanliness. Gypsy ideas about health and illness are closely related to notions of good and bad fortune, purity and impurity, and inclusion and exclusion from the group. These basic concepts affect everyday life, including the way Gypsies deal with eating and washing, physicians and hospitals, the diagnosis of illness, shopping around for cures, and coping with birth and death. PMID- 1413770 TI - Health and aging of urban American Indians. AB - Although half of the American Indian population resides off the reservation, mostly in the western states, research on the health of urban American Indians remains sparse. American Indians living in urban areas are not eligible for the federally mandated health care provided by the Indian Health Service and receive health care services in a variety of settings. This population is at high risk for many health problems, especially cardiovascular disease and diabetes mellitus. Social, cultural, and economic barriers that impede access to health care for this group, particularly for elders living in an urban setting, could be reduced if physicians improved their understanding of and communication with American Indian patients. PMID- 1413771 TI - African-American culture and AIDS prevention. From barrier to ally. AB - African Americans make up an increasing proportion of persons with the acquired immunodeficiency syndrome (AIDS). I identify and describe cultural elements such as oral traditions, multiple naming, a collective identity, extended families, and sexuality influenced by myth and exaggeration that condition African Americans' reactions to AIDS prevention. I also offer suggestions on how these cultural elements can be used for effective AIDS prevention efforts in African American communities. PMID- 1413772 TI - Mental health and illness in Vietnamese refugees. AB - Despite their impressive progress in adapting to American life, many Vietnamese still suffer from wartime experiences, culture shock, the loss of loved ones, and economic hardship. Although this trauma creates substantial mental health needs, culture, experience, and the complexity of the American resettlement system often block obtaining assistance. Vietnamese mental health needs are best understood in terms of the family unit, which is extended, collectivistic, and patriarchal. Many refugees suffer from broken family status. They also experience role reversals wherein the increased social and economic power of women and children (versus men and adults) disrupts the traditional family ethos. Finally, cultural conflicts often make communication between practitioners and clients difficult and obscure central issues in mental health treatment. Rather than treating symptoms alone, mental health workers should acknowledge the cultural, familial, and historical context of Vietnamese refugees. PMID- 1413773 TI - Dysphoria and somatization in Iranian culture. AB - Iranians express dysphoria through an undifferentiated term called narahati, meaning depressed, ill at ease, nervous, inconvenienced, or anxious. People try masking this emotion or express it in specific ways nonverbally, such as sulking or not eating. Two other dysphoric affects, sadness and anger, are not masked. Because of the social conception of persons being emotionally sensitive, the expression of narahati is guarded: expressing it not only could show that one is socially vulnerable, it could also make another sensitive empathic person narahat. The body is also sensitive, but to the physical world. Physical health is maintained by balancing a diet of "hot" and "cold" foods and avoiding exposure to cold and moisture. With the social and cultural problems brought on by revolution, war, immigration, and accommodation to a new society, Iranian refugees experience changes in family, role, status, finances, language, and other sociocultural ways of being that cause them to feel narahat and to express it verbally, nonverbally, or through somatization. Understanding Iranian conceptions of emotional and physical sensitivity will help clinicians in treating Iranian patients. PMID- 1413774 TI - Working with refugee survivors of torture. AB - Numerous factors must be taken into account to best provide for the health and well-being of refugee patients in developed countries. One issue that is rarely considered is the awful and not uncommon occurrence of political torture. Large numbers of refugees and other displaced persons are survivors of political torture, and health care professionals must be prepared for this possibility when treating refugee patients. The effects of torture are pervasive, and we provide some practical considerations for health professionals who care for survivors of torture. Specific challenges include problems relating to exile and resettlement, somatic symptoms and pain, and the "medicalization" of torture sequelae. PMID- 1413775 TI - This, that, and the other. Managing illness in a first-generation Korean-American family. AB - The use of Western medicine and of holistic traditional medicine and healing rituals is common in Korean-American families with a chronically ill member. I present a case as an example of the complexity of health management in first generation Korean-American immigrants. Immigration and acculturation issues, Confucian-related sociocultural and psychological factors, and the psychiatric diagnosis of Western specialists all elicited family conflict leading to emotional and physiologic distress. PMID- 1413776 TI - Use of traditional and modern health services by Laotian refugees. AB - Although refugee health care emerged as a special interest in the United States following the influx of almost a million Southeast Asians since 1975, few studies have been done of the influence of refugee traditions on the use of Western medical services. The illness patterns, medical beliefs, and health care behavior of a Southeast Asian refugee group, the Mien from Laos are described in this study. A cohort of 119 Mien refugees living in Richmond, California, was observed for a 6-month period. In-home interviews were undertaken about all episodes of ill health, including treatment and health care decisions. This study shows that the Mien integrate traditional healing beliefs and practices with the use of American health services. Such findings are important because the increasing cultural diversity in the United States, particularly in Western states, necessitates that health care professionals understand the importance of cultural factors for access to and the use of health care by all patients including refugees and other immigrant groups. PMID- 1413777 TI - The effect of values and culture on life-support decisions. AB - Withdrawing life support is always difficult. When patients and health professionals are from different ethnic backgrounds, value systems that form the basis for such decisions may conflict. Many cultural groups do not place the same emphasis on patient autonomy and self-determination that Western society does and find the idea of terminating life support offensive. Although physicians should never assume patients will respond in a particular way because of their ethnic background, issues of life support should be discussed in a culturally sensitive way. African-American, Chinese, Jewish, Iranian, Filipino, Mexican-American, and Korean patients were surveyed about their views on life support. The findings reported here, although not meant to be definitive, should add to health professionals' understanding about diverse beliefs around life-and-death issues. By becoming aware of this diversity of beliefs, health professionals can avoid the damage to the physician-patient relationship caused by conflicting value systems. PMID- 1413779 TI - Medical disclosure and refugees. Telling bad news to Ethiopian patients. AB - The strong value in American medical practice placed on the disclosure of terminal illness conflicts with the cultural beliefs of many recent refugees and immigrants to the United States, who often consider frank disclosure inappropriate and insensitive. What a terminally ill person wants to hear and how it is told are embedded in culture. For Ethiopians, "bad news" should be told to a family member or close friend of the patient who will divulge information to the patient at appropriate times and places and in a culturally approved and recognized manner. Being sensitive to patients' worldviews may reduce the frustration and conflict experienced by both refugees and American physicians. PMID- 1413778 TI - Ethical dilemmas in a cross-cultural context. A Chinese example. AB - Considerable attention is now being given to ethical conflicts raised by such issues as the disclosure of diagnosis and prognosis, the role of the family in making medical decisions, and the withholding or withdrawing of treatment of terminally ill patients. Already complicated, these issues take on added complexity in contexts where medical professionals and patients have differing cultural beliefs and practices. Ethical dilemmas that develop in multicultural settings have been largely unaddressed. Through the analysis of a case involving the hospital admission and death of a Chinese woman with metastatic lung cancer, we examine some of these dilemmas and their effect on the patient, family, and physicians. Many issues were raised by this case regarding the relationships among ethnic background, bioethics, and medical care. PMID- 1413780 TI - Older Russian emigres and medical care. AB - Although emigration from the former Soviet Union is dramatically increasing nationwide, little information has been reported on the medical problems of these emigres. For older emigres in particular, the medical realities of aging, in combination with cultural expectations, make the United States' medical system an arena where the stresses of emigration are expressed and help is sought. We describe the influences of culture and aging on older emigres' health and interaction with the American medical system. A qualitative, exploratory study was done of problems and issues in health care use by older Russian emigres at the ambulatory medical clinic of Mount Zion Medical Center, San Francisco. Cultural expectations and beliefs about health, adaptive health behaviors learned in the former Soviet Union, the stresses of emigration, and the medical realities of aging can result in serious problems in the care and treatment of older Russian emigres. Recommended solutions include educating emigres and health care professionals, integrating mental health services into the primary care setting, and expanding supportive services in the community such as adult day health care. PMID- 1413781 TI - Getting by at home. Community-based long-term care of Latino elders. AB - Although evidence suggests that the morbidity and mortality of Latino elders (of any Hispanic ancestry) are similar to those of non-Latino whites, Latinos have higher rates of disability. Little is known about influences on the use of in home health services designed to assist disabled Latino elders. We examine the effects of various cultural and structural factors on the use of visiting nurse, home health aide, and homemaker services. Data are from the Commonwealth Fund Commission's 1988 national survey of 2,299 Latinos aged 65 and older. Mexican American elders are less likely than the average Latino to use in-home health services despite similar levels of need. Structural factors including insurance status are important reasons, but acculturation is not pertinent. Physicians should not assume that Latino families are taking care of their disabled elders simply because of a cultural preference. They should provide information and advice on the use of in-home health services when an older Latino patient is physically disabled. PMID- 1413782 TI - The French are different. French and American medicine in the context of AIDS. AB - Medicine has often been approached as a thing apart from culture, as a uniform Western science. Within the past 10 years, we have begun to recognize that medicine is a system of beliefs and practices intrinsically linked to its larger sociocultural context. Still, it is generally perceived as uniform across North America and Western Europe. My recent research on French and American medical perspectives on the acquired immunodeficiency syndrome (AIDS) challenges this view by exploring differences in the structure of health care, the physician patient relationship, and the conceptualizations of disease, particularly AIDS. These differences are not specific to AIDS, but the disease serves to exemplify them and to act as a medium for expressing what makes French and American medicine distinct. Global epidemics such as AIDS require both international response and cross-cultural understanding. PMID- 1413783 TI - The business of preventing African-American infant mortality. AB - African-American women are twice as likely as women from other ethnic groups to have babies with low birth weights and to experience the loss of infant death. The problem is so endemic in black communities in Alameda County, California, that numerous programs have been developed over the past decade to reduce maternal risk factors and eliminate barriers to prenatal care. Despite these efforts, African-American ethnicity continues to be a major risk factor for infant mortality for reasons that are poorly understood. We take a critical look at 3 types of studies characteristic of infant mortality research: epidemiologic, studies that advocate prenatal care, and ethnomedical (cultural). We argue that the assumptions informing this research restrict the thinking about infant mortality and the political issues involved in how prevention programs are developed and structured. The persistent focus on maternal behavioral characteristics limits more in-depth analysis of the micropolitics of perinatal bureaucracies established in response to this ongoing crisis. PMID- 1413784 TI - Health policy and ethnic diversity in older Americans. Dissonance or harmony? AB - The rapid growth and diversity of the older population have long-term implications for health care policies in the United States. Current policies designed for a homogeneous population are increasingly obsolete. To ameliorate obstacles that handicap many ethnic minority elders and to provide equal access to adequate and acceptable health care, several factors need to be considered. Enhanced data collection and analytic techniques are needed. The effects of race or ethnicity must be separated from other biologic, environmental, socioeconomic, cultural, and temporal factors on health status and behavior. Health care professionals and organizations serving minority elders must continue to expand their advocacy efforts to articulate the findings and their concerns to policymakers. Policymakers must understand and acknowledge the implications of an increasingly diverse society and determine what will constitute adequate, accessible, and acceptable health care within continuing fiscal constrains. Program planning, implementation, and evaluation methods must be revised to meet future health care needs effectively and efficiently. PMID- 1413785 TI - A season in the life of a migrant farm worker in California. AB - There is an erroneous but widespread belief that in the past few decades California agriculture has become increasingly mechanized and reduced its need for migrant labor. Steeply increasing demand, however, for specialty fruit and vegetable crops, which are labor-intensive, has actually increased the need for migrant workers, who come mainly from Mexico. A case study of a young migrant describes the dismal work, economic, and living conditions such workers typically endure and the possible health consequences of those conditions. PMID- 1413787 TI - [Nephrotic syndrome with mesangial hyperplasia and an unfavorable outcome]. AB - In a group of 109 children with the nephrotic syndrome caused by mesangial hyperplasia 5 cases with unfavourable outcome were observed. The follow-up was from 3 years to 11 years. In all children no remissions of the syndromes were obtained after treatment with prednisone, methylprednisolone pulses, immunosuppressants. They had hypertension poorly responding to hypotensive drugs, and chronic renal failure developed with early progression to terminal renal failure. In three children subjected to renal transplantation the signs of the nephrotic syndrome returned, in two of them biopsy of the renal graft demonstrated evidence of mesangial hyperplasia, and in one case vascular rejection and extracapillary proliferation of cells with presence of semilunar hyperplasia. PMID- 1413788 TI - [Trans-esophageal stimulation of the heart in pre-excitation syndrome]. PMID- 1413786 TI - Occupational health problems among migrant and seasonal farm workers. AB - Migrant and seasonal farm workers are one of the most underserved and understudied populations in the United States. The total US population of such farm workers has been estimated at 5 million, of whom about 20% live or work in California. Farm workers perform strenuous tasks and are exposed to a wide variety of occupational risks and hazards. Low socioeconomic status and poor access to health care also contribute to existing health problems in this population. Potential farm work-related health problems include accidents, pesticide-related illnesses, musculoskeletal and soft-tissue disorders, dermatitis, noninfectious respiratory conditions, reproductive health problems, health problems of children of farm workers, climate-caused illnesses, communicable diseases, bladder and kidney disorders, and eye and ear problems. Few epidemiologic studies exist of these occupational health problems. No comprehensive epidemiologic studies have assessed the magnitude of occupational health problems among migrant and seasonal farm workers and their dependents. Although the migratory nature of this population makes long-term studies difficult, the development of standardized data collection instruments for health consequences and scientific assessment of farm work exposures and working conditions are vital to characterize and reduce the occupational health risks in farm workers. PMID- 1413789 TI - [Intermediate lymphocytic lymphoma]. AB - The characteristic features are presented of intermediate lymphocytic lymphomas which have suggested the pathomorphological and clinical peculiarity of this disease entity. They occur in two forms: diffuse and nodular which are two phases in the development of the disease. The phenotypic and karyotypic characteristics of these lymphomas resemble those of chronic lymphocytic leukaemia, but their more malignant course is similar to that of centrocytic lymphomas. PMID- 1413790 TI - [Effect of lead on thyroid function]. AB - Lead in organic and inorganic compounds is a health risk factor leading after high-grade exposure to poisoning. It can accumulate in the organism and exert toxic effects, especially on the haemopoietic system and nervous system. Its action includes damage to cell membranes and disorders of the oxidoreductive processes in the cells. Hypothyroidism occurring in subjects with occupational exposure to lead may evidence a negative effect of the element on thyroid function. PMID- 1413791 TI - [Selected clinical aspects of modern teratology]. PMID- 1413792 TI - [Systemic arteriovenous fistula of the brain as cause of circulatory insufficiency in the newborn]. PMID- 1413793 TI - [Protein in infant food--contemporary observations]. PMID- 1413794 TI - [A case of esophageal pemphigus]. AB - A case of oesophageal pemphigus was observed in a man aged 76. Attention is called to the rarity of this disease and resulting diagnostic difficulties. PMID- 1413795 TI - [A case of Hashimoto struma coinciding with limited scleroderma]. AB - In a female patient aged 43 years severe hypothyroidism was caused by Hashimoto struma. She had also cutaneous changes suggestive of collagen disease. On the basis of clinical manifestations, laboratory investigations and histological examinations coexistence was diagnosed of two autoimmunological diseases. Stress is laid on diagnostic difficulties and choice of management. PMID- 1413796 TI - [Visceral toxocariasis in three children]. PMID- 1413797 TI - [A case of malignant melanoma of the clitoris]. PMID- 1413798 TI - [The effect of hormones on the gastrointestinal mucosa]. AB - Proliferative effects of hormones on the gastrointestinal mucosa are discussed according to literature data. There are presented the trophic effects of gastrin, cholecystokinin, secretin, enteroglucagon, somatostatin, growth hormone, thyroxine, peptide YY, epidermal growth factor and submaxillary growth factor. PMID- 1413799 TI - [The fight against disease as applied to the plague epidemic in Wroclaw in 1542 1543]. PMID- 1413800 TI - [Different course of myocardial infarction in old age]. AB - For the assessment of the peculiarities of acute myocardial infarction in patients aged over 60 years 100 patients with this disease treated at the Department of Internal and Occupational Diseases, Silesian Medical Academy were compared with 100 patients aged below 60 years. The location of myocardial infarction was similar in both groups. In the younger group premature ventricular beats were more frequent while in the older group supraventricular or ventricular tachycardia and left bundle branch block were more frequent. The death rate was much higher in the older group. PMID- 1413801 TI - [Conservative treatment of arterial occlusion with streptokinase administered intra-arterially]. AB - The effectiveness of conservative treatment of the occlusion of peripheral arteries with streptokinase administered intra-arterially was assessed in 16 cases. In 11 cases the blood flow in the extremity was returned (68.7%). Good therapeutic results were obtained in properly selected cases. PMID- 1413802 TI - [Effect of hemodialysis on somatosensory evoked potentials of medium and long latency]. AB - In 16 patients with terminal renal failure aged from 21 to 74 years maintained on haemodialysis programmes for 2 to 60 months somatosensory evoked potentials were studied after stimulation of the median nerve immediately before and after haemodialysis. The central conduction time, the P 45-N 60, P 100-N 140-P 200 complexes and the P 300 wave were evaluated. The results were compared with those in 16 healthy volunteers aged 20 to 66 years. In the patients on haemodialyses the evoked somatosensory potentials of medium and long latency differed statistically significantly from those in the control group, but not direct effect of haemodialysis on these potentials was found. PMID- 1413803 TI - [Allergic reactions to teniposide (VM-26) in children with neoplasms]. AB - Allergic reactions of dramatic intensity were observed in 5 children treated with Teniposide (VM-26) for acute lymphoblastic leukaemia and histiocytosis X. In the further treatment this drug was replaced with epoxide, a cytostatic agent which is also a podophyllin derivative but in other chemical formulation. In none of these patients the allergic reaction returned. PMID- 1413804 TI - [Morphologic appearance of intestinal microvilli in children with coeliac disease and secondary malabsorption syndromes after gluten-free diet and gluten challenge]. AB - The glycocalyx and the structure of the microvilli were analysed in electron microscopy in 122 children with coeliac disease and secondary syndromes of malabsorption. Slight differences were noted in glycolayx structure between both groups of children. In children with coeliac disease its reduction was noted (after gluten challenge). Changes were observed also in the structure of the microvilli. They were lower and often with abnormal shape in coeliac disease, while they were high and of normal structure in secondary malabsorption syndromes. PMID- 1413805 TI - [Changes in the visual system of children with subacute sclerosing panencephalitis]. AB - The results of ophthalmological examinations were compared in 20 children aged 6 to 13 years with SSPE. The examinations in the first phase of the disease demonstrated fundus changes with presence of choked disc in 4 cases, papilloedema in 4 cases, uveitis in 1 case, retrobulbar optic neuritis in 1 case (in this case ophthalmological changes developed 4 months prior to the onset of typical neurological sings. PMID- 1413806 TI - [Diagnosis of inborn errors of metabolism: necessity or luxury?]. PMID- 1413807 TI - [Clinical suspicion of inborn errors of metabolism]. AB - A number of inherited metabolic disorders are diagnosed by means of the nationwide newborn screening programme, usually before the first clinical signs occur. As for the rest of the varied metabolic disorders, knowledge and intuition of the paediatrician is a prerequisite for selection of patients for further metabolic investigation (selective screening procedure). Clinical symptoms of the most important metabolic diseases can be classified according to their pathophysiological background as: "intoxication type, energy deficiency type, storage type, neurodegenerative type". Especially in the first year of life, clinical features are unspecific: psychomotoric retardation, muscular hypotonia, cerebral convulsions, recurrent vomiting, sepsis-like conditions. In these cases indication for metabolic screening is broad. Especially in older children some clinical symptoms can be specific for a metabolic disorder: distinctive odour of urine, changes in hair, skin or eyes, organomegaly, skeletal changes. Recently, Reye-like syndrome, stridor, macrocephaly and vague, cerebral ischaemic episodes have been described in association with a metabolic defect. In conclusion, experience has shown that only a small number of metabolic disorders will be diagnosed from the typical clinical picture alone. In most cases a selective screening procedure leads to diagnosis because initial symptoms are unspecific. PMID- 1413808 TI - [Differential diagnosis and therapy of various forms of hyperphenylalaninemia: facts and fiction]. AB - The various conditions which can lead to elevated blood phenylalanine (PHE) levels must be differentiated promptly in the neonatal period so that the correct treatment can be implemented as soon as possible. In order to exclude the rare tetrahydrobiopterin (BH4) deficiency, it is advisable to perform a BH4 loading test and to determine the renal excretion of pterins, as well as the dihydropteridine reductase activity in erythrocytes. The practical consequence of differentiating the various types of PHE hydroxylase deficiency is that with both phenylketonuria (PKU; PHE greater than 20 mg/dl) and hyperphenylalaninemia (HPA) with PHE levels above 15 mg/dl a diet restricted in PHE is initiated, whereas HPA infants with PHE levels below 8 mg/dl are fed normally. In the case of PHE concentrations between 8 and 15 mg/dl standardized protein intake can be used to decide whether a diet restricted in PHE or only a restriction of protein intake has to be instituted. Optionally a protein challenge can be performed at the age of six months in order to evaluate the individual PHE tolerance. Psychometric investigations of PKU patients after diet discontinuation at different ages, as well as animal studies are in favour of a diet-for-life. The diet in PKU patients is known to lead to some side effects such as bony changes and amino acid imbalance, as well as deficiency of selenium and carnitine. Finally, great efforts have to be made in order to avoid the increasing danger of PHE embryofetopathy in the offspring of PKU mothers (maternal PKU). PMID- 1413809 TI - [25 years Austrian screening program for inborn errors of metabolism at the Vienna University]. AB - The results are presented by the Austrian screening program for inborn errors of metabolism, which is one of the oldest and most comprehensive in the world. At present, the program comprises screening for the following diseases: phenylketonuria, galactosemia, homocystinuria, maple syrup urine disease, hypothyroidism, biotinidase deficiency. The results of the program with regard to diagnosed cases are presented: in total, 747 carriers of various inborn errors of metabolism have been detected by means of the Screening Program and were referred for therapy where appropriate. PMID- 1413810 TI - [Long-term results in children with classical galactosemia]. AB - Galactosemia due to uridyl-transferase deficiency was detected in 47 patients between 1/1/1967 and 31/12/1988. The condition took a fulminant course in 31 patients and 10 infants in this group died between the 6th and the 18th day of life. The determination of uridyl-transferase in 36 patients confirmed the diagnosis. Exchange blood transfusion was undertaken in 25 infants because of hyperbilirubinemia, septicemia or neurological symptoms. 5 of the 31 children had a cataract. In most cases the lactose-free diet was commenced in the 2nd week of life. 27 patients were followed up with respect to somatic and intellectual development. Gonadal function was investigated in 5 patients; hypergonadotropic hypogonadism was found in the 4 girls. PMID- 1413811 TI - [Vasoactive drugs with an effect on the prostaglandin system]. AB - The balance between prostaglandin (PG)I2, a potent vasodilator and inhibitor of platelet aggregation mainly produced by endothelial cells, and thromboxane (TX)A2, a vasoconstrictor and inducer of platelet aggregation and adhesion synthesized predominantly by platelets, seems to be relevant for the regulation of vessel tone and platelet aggregation. PGE2 has vasodilating properties, too. Thus, substances affecting the biosynthesis of PG and TX may have prophylactic and therapeutic, but also detrimental effects with regard to hypertension and atherosclerosis. A mechanism of action which is related to the PG system is discussed for a number of antihypertensive agents, e.g. propranolol, angiotensin converting enzyme inhibitors, furosemide and cicletanine. The vasoprotective effect of inhibition of platelet cyclooxygenase by acetylsalicylic acid is well known. Calcium antagonists, dipyridamole, estradiol, aprotinin and interferon have also been reported to possibly exert beneficial effects on PG/TX levels, while cyclosporin A and streptokinase have shown undesirable interactions with the PG system. PMID- 1413812 TI - [Risk factors of atherosclerosis--primary examination of Vienna employees]. AB - In the course of an atherosclerosis intervention study, a basic medical check-up of 2105 out of 4800 employees of a Viennese banking house was carried out (37.1 +/- 11.0 years, 54.6% females). Apart from liver and kidney function parameters, an extensive lipid status was determined, the blood pressure was measured, and a cardiovascular-centered case history ascertained. The mean cholesterol level in females was 208.3 +/- 54 mg/dl and that in males was 226.8 +/- 61.1 mg/dl. The HDL-cholesterol level in males was 43.8 +/- 11.9 mg/dl; that in females (54.9 +/- 13.4 mg/dl) was significantly higher. The mean value of LDL-cholesterol in the entire group was 141.6 +/- 51.4 mg/dl and it was significantly higher in males, as well as in participants with known hypertension. 33.4% of the persons stated that they smoked. The obtained data will serve not only to discover potential interrelations between the individual risk factors of atherosclerosis in Austria, but also in particular as a basis for interventional strategies on the part of the company's medical services. PMID- 1413813 TI - Risk factors for atherosclerosis in female type II diabetic patients with incipient diabetic nephropathy. AB - Risk factors for atherosclerosis were investigated in a group of 17 female Type II diabetic patients with microalbuminuria-urinary albumin excretion (UAE) in the range of 30-300 mg/day, and in a control group including 15 Type II diabetic females with UAE less than 30 mg/day. Significantly increased mean concentrations of total and LDL-cholesterol were measured in the group with microalbuminuria (p less than 0.05). Also mean levels of some other cardiovascular risk factors (systolic blood pressure, fibrinogen, apolipoprotein B, triglycerides and uric acid) were higher in the group of patients with microalbuminuria, although the differences in comparison to the control group did not reach the level of statistical significance. In the multiple stepwise regression analysis log transformed UAE values correlated significantly with three independent factors- uric acid (p less than 0.01), fibrinogen (p less than 0.05), and systolic blood pressure (p less than 0.05). It is concluded that a slight increase in the levels of a number of cardiovascular risk factors observed in incipient diabetic nephropathy suggests an additive effect favouring atherogenesis. PMID- 1413814 TI - [Development of arterial revascularization of the myocardium at the Linz general hospital. Personal experiences with 1000 patients]. AB - Arterial revascularization of the myocardium, particularly the use of the internal mammary artery (IMA) as a bypass graft in coronary artery surgery has become an established procedure over the past decade. From March 1986 to June 1991, of 2070 patients who underwent coronary heart surgery at our department, revascularization of the myocardium was performed with an IMA graft in 1000 cases, whereby the percentage increased from 10.4% in 1986 to 75.0% in 1991 (p less than 0.01). The range of indications gradually widened throughout the period, age no longer being a contradiction today. One reason for this development is the substantial improvement in IMA preparation technique. No increase was found in rethoracotomy rate or in the rate of perioperative infarctions. The mean age of patients receiving an IMA graft increased from 55.2 years (1986) to 64.7 years (1991) and therefore reflects the change in ranges of indication. 54 IMA jump grafts were anastomosed, in 30 cases bilateral IMAs were used and the IMA was implanted as a free graft twice. In the future these successful results with the implementation of IMA grafts will lead to a further displacement of the saphenous vein as main bypass material. PMID- 1413815 TI - [Snuff aspiration as a cause of recurrent pulmonary infiltrations in a 60-year old patient with chronic renal failure]. AB - Pulmonary infiltrations associated with renal failure demand several diagnostic procedures to exclude autoimmune disorders affecting both organ systems or to find an infectious cause of the disease. We report the case of a 60 year-old man with chronic renal failure and recurring pulmonary infiltrations. On admission to hospital all diagnostic parameters for systemic vasculitis, infectious or neoplastic disease were negative, including the histological report on transbronchial biopsies. Eventually, follow-up biopsies taken 3 months later showed vegetable fibres and necrosis due to intensive snuff abuse during the previous months. After the patient stopped taking snuff the pulmonary infiltrations improved quickly. Uraemic neuropathy, which may have facilitated aspiration, as well as the reduced pulmonary and systemic defence mechanisms due to chronic renal failure probably contributed to a considerable degree to the development of pulmonary infiltration. PMID- 1413816 TI - [Staphylococcus epidermidis infection. Results of three groups evaluated according to APACHE II--severity of disease classification system--with reference to risk, mortality and prognosis]. PMID- 1413817 TI - [Report of 111 patients with multiple cancers of the first medical department of the Vienna-Lainz nursing home 1981-1987]. AB - After a short synopsis of the literature we describe 111 patients with multiple primary cancer and compare these patients with 804 patients with solitary cancer admitted over the same period. Patients who developed primary cancer at a younger age are more prone to developing a second cancer than patients who developed cancer first at an older age. This concerns younger women with breast or genital cancer, who are much more likely to develop a second cancer than older women; nevertheless these women have a more favourable prognosis. As the great majority of patients were already over 70 at the time of diagnosis of the second cancer, the prognosis of geriatric diseases has become of considerable significance. We present a detailed investigation of the interrelations between the first and second cancer, also between oncological and geriatric diseases. PMID- 1413818 TI - [Successful treatment of HIV-associated pneumocystis carinii pneumonia with dapsone plus trimethoprim]. AB - Standard treatments of HIV-associated Pneumocystis carinii pneumonia (PCP) consist of high dose intravenous or oral cotrimoxazole or intravenous pentamidine. Both treatment modalities are associated with a high incidence of side effects which strengthen the need for alternative therapies. Since April 1987 we have used the combination of dapsone plus trimethoprim (DP+TMP) as primary treatment for PCP in patients who could be managed on an outpatient basis. We report the results of an analysis of the efficacy and toxicity of this treatment in 20 episodes of PCP in 18 patients. PCP was diagnosed by identification of the pathogens in bronchoalveolar lavage specimens. Chest X-ray revealed bilateral involvement in 11 and unilateral in 7 cases and no infiltration in one patient. Treatment over three to four weeks was successful in 14 of 20 PCPs (70%). In six cases (30%) treatment was changed to another regimen after a mean of seven days due to a maculopapular rash (n = 2), haematotoxic side effects (n = 2), persistent fever (n = 1) and for unexplained reasons (n = 1). Less severe side effects not causing a change in treatment were a slight to moderate neutropenia (n = 10), a moderate elevation of liver enzymes (n = 2) and a well tolerated rash (n = 2). The success rate of DP+TMP was in the same range as it is known for the standard regimens, whereas the rate of severe side effects appears to be lower. The results suggest that in AIDS patients DP+TMP may be used as first line treatment of PCP which is not severe enough for hospitalisation. PMID- 1413819 TI - [Biochemical and immunohistochemical detection of epidermal growth factor receptor in breast and ovarian tissue]. AB - The epidermal growth factor receptor (EGFR) was assessed in 52 breast and 46 ovarian biopsies by the radio ligand binding assay and/or the immunoperoxidase technique. A direct comparison of the two methods was undertaken in 27 breast and 32 ovarian biopsies. The results of both methods correlated positively (r = 0.59) in malignant tumours (n = 34), but not in benign lesions (n = 16) nor in normal tissues (n = 9). The different results may be explained by the fact that different aspects were measured by the two methods, while the biochemical assay assessed the receptor binding capacity, the immunohistochemical method detected an EGFR epitope. Since the histochemical method allows the localization of EGFR positive cells and the biochemical assay gives a quantitative measure, both methods together give more information on the receptor situation. A comparison of the results of these methods used simultaneously, rather than alternating one method with another improves the degree of accuracy of evaluation. PMID- 1413820 TI - [Human immunodeficiency virus]. PMID- 1413821 TI - [Risk factors for the development of diabetic retinopathy in patients with insulin-dependent diabetes mellitus treated with continuous subcutaneous insulin infusion]. AB - During a one year observation period, the retinal status, glycosylated hemoglobin levels (HbA1), hypoglycemias, lipid values, blood pressure and clinical abnormalities of IDDM (insulin dependent diabetes mellitus) patients treated by CSII (continuous subcutaneous insulin infusion) were documented. In 70 (out of n = 81) patients 137 retinal follow-up examinations were performed and evaluated. In 86.1% of those patients, CSII appeared to have a positive influence on their retinal status. In 14.6% (8.6% with background retinopathy + 5.8% with proliferative retinopathy) improvement of a pre-existing retinopathy could be seen. The diabetes duration itself seemed to have no influence on development or progression of diabetic retinopathy, but elevation of HbA1 or serum triglyceride levels, as well as elevated systolic blood pressure leaded (on a medium term base) to statistically significant deterioration or development of retinopathy. In addition, hypoglycemias and impaired renal function have to be seen as risk factors potentiating each other. CONCLUSION: Besides the treatment of cardiovascular risk factors, getting normal HbA1 values while avoiding hypoglycemia must be the major aim in therapy management to prevent microangiopathy. In certain cases, even patients with severe retinopathy might benefit from CSII. When blood sugar levels are carefully lowered during the first months, no deterioration of the retinal status is seen in patients with long-term metabolic decompensation. PMID- 1413822 TI - [Surgical treatment of glossopharyngeal neuralgia]. AB - Glossopharyngeal neuralgia is a rare disease which is characterized by severe paroxysmal pain attacks in the distribution of the 9th cerebral nerve. Although uncommon, the condition has to be considered in the differential diagnosis of various craniofacial neuralgias. The purpose of this study was to describe 3 cases of glossopharyngeal neuralgias and to discuss its diagnosis and therapy. Various surgical therapeutic procedures have been described, including neurotomy of the glossopharyngeal nerve in the frontal neck, thermocoagulation of Andersch's ganglion, and para-pontine neurotomy (Dandy). Because of its good results and low incidence of recurrences, microvascular decompression (Jannetta) is considered the procedure of choice. PMID- 1413823 TI - Cerebral palsy: improved outcome by early detection of latent failure of psychomotor development in infants. AB - A prospective cohort study was performed to evaluate the results of a new screening system for latent psychomotor disturbances in infancy developing into cerebral palsy (CP). The system has been based on an early diagnosis within the first 2 months of life with a subsequent follow-up. All liveborn children were screened and suspect cases were immediately referred to detailed neurological examination. With the new screening system implemented within 1988 to 1989, the incidence of cerebral palsy in the area could be halved as compared to 1980 to 1986 (0.26% vs. 0.52% of liveborn children respectively). Out of 4,166 liveborn children, 527 newborns had to be referred to neurologic examination, thereof 460 required follow-up and 228 had to be treated. In only 11 of the children CP was diagnosed at the age of 15 months. 8 of the CP children presented signs of serious neurologic disturbance at birth and were considered as "requiring high tech use". A latent psychomotor disturbance developing slowly into CP during the first year of life occurred but in 3 children, 2 of them having relatively favorable prognosis; this group was termed as "requiring skilled clinical organization". Premature children (under 37 weeks of gestational age) had an 82% share on our recent CP patients. PMID- 1413824 TI - [Does a supportive "muscle corset" prevent spinal complaints?]. AB - By strengthening trunk muscles, we hope to prevent back pain. The logic behind this argument is, however, fragmentary. The scientific evidence for the effectiveness of such measures is conflicting. Rigorous trials provide little indication as to the correctness of the above thesis. Thus further research on this important matter is necessary. Until it is available, primary prevention programs based on trunk strengthening exercise are lacking a scientific basis. PMID- 1413825 TI - Differentiated thyroid carcinoma in children and adolescents. AB - From 1936 to 1990, 89 children and adolescents (72 girls and 17 boys) were treated for differentiated thyroid carcinoma at the University of Michigan Medical Center; 58 of these patients were first reported in 1971. Thirty (34%) patients had previously received external irradiation to the head and neck, although only 1 (3%) patient of the last 33 patients seen had this history. Patients first presenting from 1971 to 1990 had less advanced disease than those seen earlier. Also, during this time period, the rate of initial palpable cervical adenopathy fell from 63% to 36%, local infiltration of primary cancer from 31% to 6%, and initial pulmonary metastases from 19% to 6%. The incidence of cervical nodal metastases has remained 88% for 54 years. Papillary or the follicular variant of papillary carcinoma was found in 93% of all patients. Seventy-nine (89%) patients had total or completion total thyroidectomy. Surgical management of lymphatic metastases varied from regional excision of nodes to radical neck dissection. The overall rate of permanent accidental recurrent laryngeal nerve palsy and hypoparathyroidism was 4.5%, although neither has occurred in a child or adolescent undergoing surgery at the center in the past 25 years. The most recent 33 patients had a low rate of local/regional persistence or recurrence. Cervical nodal persistence occurred in 21%; there were no thyroid recurrences. Eighty-two percent of patients received 131I. The long-term mortality rate was 2.2%. We continue to advocate total thyroidectomy, cervical lymph node dissection, and postoperative 131I therapy as the most conservative treatment regimen for children with differentiated thyroid carcinoma. PMID- 1413826 TI - Causes of failed primary exploration and technical aspects of re-operation in primary hyperparathyroidism. AB - Hypercalcemia was corrected in 62 (90%) of 69 patients after re-operation for primary hyperparathyroidism during a mean follow-up of 6.3 years. Failed primary exploration was mainly due to inadequate visualization of the pathological parathyroid glands, often in association with misleading or absent peroperative histology. Other causes included seeding of parathyroid adenoma tissue, truly recurrent adenomas, and recurrent hyperplasia, especially in patients with multiple endocrine neoplasia type 1. A considerable number of parathyroid glands missed at the primary operations were subsequently found in essentially normal positions. Ectopic superior glands were most frequently positioned para esophageally or retro-esophageally, while abnormally placed inferior glands were generally situated within or close to the thymus. Glands in 3 patients were dissected from around the large vessels in the mediastinum. Concomitant thyroid procedures during the primary operation yielded few abnormal parathyroids and made the re-exploration considerably more difficult. We suggest a semilateral approach and caudal identification of the recurrent laryngeal nerve to reduce the hazards of difficult parathyroid re-operations. Mediastinal exploration may require total removal of the thymus and careful dissection of the middle mediastinum. PMID- 1413827 TI - Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications. AB - Activating mutations of ras-genes (Kirsten-ras, Harvey-ras, N-ras) and genes encoding for the alpha subunit of G-proteins (Gs, Gi2, Gi3, Go, Gz) were assessed in 32 differentiated thyroid cancer (DTC) tissues from German (n = 22) and American (n = 10) patients. Gs-protein (GSP) and/or ras mutations were found in 69% of all tissues with a heterogeneous distribution pattern. An increased prevalence could be demonstrated in metastatic (8 of 9 mutation positive) when compared to localized disease (13 of 23 mutation positive) (p less than 0.001) and in patients greater than 50 years of age (16 of 18 mutation positive), when compared to younger patients (6 of 14 mutation positive) (p less than 0.001). No activating mutations were found on H-ras and K-ras genes nor on genes encoding for the alpha subunits of Gi2, Gi3, Go, and Gz. Differentiated thyroid cancer tissue from German patients revealed a higher prevalence for GSP mutations (73%) than did DTC from American patients (20%) (p less than 0.001). We demonstrated a high frequency of ras and GSP mutations in DTC and suggest that these mutations may contribute to our basic understanding of this disease and might initiate a new search for more rational and individualized therapeutic approaches in patients with DTC. PMID- 1413828 TI - Outcome of long standing solitary thyroid nodules. AB - We investigated the outcome of long standing palpable solitary thyroid nodules by surveying 441 patients and examining 140 patients who had untreated thyroid nodules for 15 +/- 4.5 years. In our clinical survey, the most common outcome was disappearance of the thyroid nodule (38.3%). Also a significant number of patients (36.3%) underwent surgery in other hospitals. Five (1.1%) patients died of thyroid cancer. When thyroid nodules were re-examined, most nodules indeed decreased in size or disappeared; however, 13% of nodules increased in size. Ultrasound of the nodules showed that most solitary nodules were multiple and partially cystic and solid. There was an increased incidence of calcification in long standing nodules. Thyroid cancer was found by fine needle aspiration biopsy in 26.3% of enlarging nodules and 6.4% of nodules without changing size. The risk of cancer decreased when the size of the nodule decreased. A total of 15 patients with suspicion of malignancy underwent surgery. Surgical procedures were lobectomy, near total thyroidectomy, or resection of nodules with or without modified neck dissection. Seven patients had papillary carcinoma and 2 patients with benign cytology had microscopically evident papillary carcinoma. In our study, the majority of palpable solitary thyroid nodules tended to decrease in size; these nodules do not require treatment. Enlarging solid nodules are a definite risk for thyroid cancer. If the size of the nodule remains the same, judicious approach with fine needle aspiration biopsy is needed. PMID- 1413829 TI - Follicular tumors of the thyroid gland: diagnosis, clinical aspects and nuclear DNA analysis. AB - From 1985 to 1990, 169 patients underwent surgery for follicular thyroid tumors at the Department of Surgery, Karolinska Hospital, Stockholm, Sweden. Nine of the patients had tumors which were diagnosed as follicular carcinoma, 4 of whom had recurrences in the neck region. In 6 of the patients the carcinomas were diagnosed as widely invasive and in 3 patients as minimally invasive. Of the 160 patients with follicular adenomas, 21 adenomas were of oxyphil type ("Hurthle" adenomas), 17 adenomas were diagnosed as "atypical", and 6 adenomas were classified as being both "atypical" and having oxyphil cell differentiation. The nuclear DNA content was measured with image cytometry and/or flow cytometry. Six of the 9 carcinomas were euploid and 3 were aneuploid. In the adenoma group, 32 (20%) were aneuploid. Thus 38% of all adenomas showed atypical cellular features, oxyphil cell differentiation, and/or aneuploid nuclear DNA pattern. None of the patients with adenomas have shown any sign of recurrence. In the present prospective study, the nuclear DNA content could not discriminate between a benign and a malignant follicular tumor, and was of limited value in predicting prognosis in the patients with follicular carcinoma. Still, the best way to establish a diagnosis and to predict prognosis is to surgically remove the follicular tumor for a proper histopathological examination. PMID- 1413830 TI - Recurrent renal hyperparathyroidism and DNA analysis of autografted parathyroid tissue. AB - In spite of recent therapeutic advances, severe overt secondary hyperparathyroidism due to chronic renal failure necessitates parathyroidectomy and recurrent hyperparathyroidism is one of the most significant problems in this patient population. In the present study, the incidence of recurrent hyperparathyroidism was evaluated in relation to the histopathological features. Image cytometric DNA analysis was performed to estimate the proliferative potential of parathyroid tissue. The study comprised 248 patients who underwent parathyroidectomy from 1973 to 1991. The frequency of recurrent hyperparathyroidism after subtotal parathyroidectomy was 4 (21.1%) of 19 patients, the rate of graft-dependent recurrence after removal of residual parathyroid tissue with forearm autograft was 2 (50%) of 4 patients. The frequency of graft-dependent recurrence after total parathyroidectomy with forearm autograft was 16 (7.5%) of 212 patients. The frequency of recurrence was significantly higher (p less than 0.01) when nodular hyperplastic parathyroid tissue was autografted (17 of 68 patients, 25%) than when diffuse-hyperplastic tissue was grafted (1 of 105 patients, less than 1%). All 58 specimens subjected to image cytometric DNA analysis showed a diploid nuclear pattern cytometrically. However, the relative number of scattered cells that displayed cytometric nuclear DNA values outside the main diploid histogram peak was significantly greater (p less than 0.01) in nodular hyperplastic tissue before being autografted and in parathyroid tissue removed at re-operation performed for recurrence than in diffuse hyperplastic tissue. These clinical findings and results of DNA analysis clearly indicated that nodular hyperplastic parathyroid tissue has a higher growth potential, and it is concluded that to prevent graft-dependent recurrence, the nodular type of hyperplastic tissue should not be autografted. PMID- 1413831 TI - Non-Hodgkin's lymphoma of the thyroid: is more than biopsy necessary? AB - Whereas excisional surgery and radiotherapy have resulted in a favorable outcome when non-Hodgkin's lymphoma of the thyroid (NHLT) is confined to the thyroid gland, controversy persists over the potential advantage of aggressive debulking in favor of diagnostic biopsy alone when disease cannot be completely resected. Our aims in this study were to delineate the present role of surgery in NHLT in pre-operative staging, the impact of the extent of resection on achieving complete remission and cause-specific survival, and patterns of failure. All 62 patients who underwent primary surgery for NHLT at the Mayo Clinic between 1965 and 1989 were analyzed. By postoperative staging, 50 patients were stage IE or IIE. Overall survival was 53% and 46% at 5 and 10 years; 80% for stage IE confined to the thyroid, 58% for stage IE-extrathyroid, 50% for stage IIE, and 36% for stages IIIE and IVE. Complete remission was achieved in 88% of patients who underwent diagnostic biopsy plus adjuvant therapy alone compared to 85% for patients in whom debulking plus adjuvant therapy was used. There was no difference in cause-specific survival in these two groups or in cause-specific survival in two subgroups who achieved complete remission. Relapse after complete remission occurred in 12 (26%) of 46 patients, only 2 of whom survived long-term after salvage therapy. The role of surgery in NHLT is diminishing and advances that will increase complete remission and relapse-free survival will not likely involve more aggressive surgical resections. PMID- 1413832 TI - Dynamics of parathyroid hormone release and serum calcium regulation after surgery for primary hyperparathyroidism. AB - Analysis of 14 patients with primary hyperparathyroidism (HPT) prior to and during the first year after parathyroid surgery disclosed that the operation was associated with rapid reductions of intact serum parathyroid hormone (PTH) and total serum and ionized plasma calcium values. A decreased urinary calcium excretion, a gradual elevation of renal calcium reabsorption, a transient reduction of serum calcitriol, and a late increase in 25-hydroxycholecalciferol values were also noted. Dynamic tests of parathyroid function by EDTA infusion and an oral calcium load revealed a sigmoidal relationship between serum PTH and calcium levels, and that parathyroid surgery induced considerable changes in both the position and slope of the dose-response curve. It was also apparent that PTH release was submaximally stimulated event at periods of hypocalcemia. The findings substantiate that adjustments of PTH release to acute alterations of serum calcium occur along the prevailing dose-response relationship, while stimuli being maintained for longer periods of time induce compensatory shifts in the position and slope of this curve. It is further suggested that unknown factors with PTH-like function may participate in the calcium regulation after surgery for primary HPT. PMID- 1413833 TI - Unilateral neck exploration for primary hyperparathyroidism: analysis of a controversy using a mathematical model. AB - Most endocrine surgeons explore both sides of the neck and identify all parathyroid glands when operating on patients with primary hyperparathyroidism. Others, however, advocate the unilateral approach, i.e., if an adenoma and a normal gland are identified, the contralateral side is not explored. We analyzed the strategy of the unilateral approach using a mathematical model to determine the variables that influence the probability of missing a tumor on the unexplored side of the neck. Assuming the frequency of single adenoma is 80%, hyperplasia 14%, double adenomas 4%, triple adenomas 1%, and carcinoma 1%, and the probability of missing a tumor on the explored side is 5%, we found that: 1. Only 41% of the patients treated by the unilateral approach undergo unilateral exploration. This is increased to 62% when a localization study with a sensitivity of 80% is used pre-operatively. 2. The probability of missing a tumor on the unexplored side of the neck parallels the prevalence of multiple adenomas. Half of the patients with triple adenomas and two-thirds of the patients with double adenomas will have a missed tumor when treated by the unilateral approach. 3. Patients who undergo unilateral exploration have an additional 7% to 8% probability of missing a tumor that would have been found if bilateral exploration is performed. This risk is lowered to 2% by a pre-operative localization study that is 80% sensitive. 4. A prospective study will require 684 patients, randomized to the unilateral or bilateral approach, to have an 80% statistical power (alpha = 0.05, beta = 0.20) of detecting a difference between a 5% and a 10% risk of missing a tumor. PMID- 1413834 TI - Adrenal cortical carcinoma in Norway, 1970-1984. AB - Adrenal cortical carcinoma is a rare and highly malignant tumor. This retrospective study includes 99 patients (57 males and 42 females) reported to The Cancer Registry of Norway during the 15 year period from 1970 to 1984. The age adjusted incidence was 1.5 per million per year. Eighty-one patients were diagnosed with adrenal cortical carcinoma when still alive. In 18 cases the diagnosis was first made at autopsy. Median age at diagnosis was 54 years (range 2-88 years) with a slight male predominance. Information about initial symptoms was available in 67 patients, of whom 26 patients (18 females and 8 males) presented with clinically functioning tumors, the Cushing syndrome and virilization being most frequently encountered. Only 28 (35%) of 81 patients diagnosed when still alive had tumors confined to the adrenals. Half of the patients had distant metastases, with lungs and liver being the most frequent sites. Sixty-one patients underwent surgery; 51 patients had a radical or debulking operation and 10 patients had laparotomy with tumor biopsy. After a complete follow-up for at least 6 years (range 6-21 years), only 9 patients were still alive. Early stage (Stage I and II) and curative resection had a significant impact on the outcome of this disease. To improve prognosis, early diagnosis and radical surgery, if feasible, are needed. PMID- 1413835 TI - Hurthle cell (oxyphilic) papillary thyroid carcinoma: a variant with more aggressive biologic behavior. AB - The latest World Health Organization International Classification defines papillary thyroid carcinoma by its "follicular cell differentiation...as well as characteristic nuclear changes". However the oxyphilic (Hurthle cell) papillary carcinoma have nuclei which generally resemble the nuclei seen in oxyphilic follicular carcinomas, and such oxyphilic papillary tumors may behave more aggressively than typical papillary cancers. To further characterize these rare tumors, we identified during a 32-year period 22 patients with oxyphilic papillary cancer and compared them with 1,084 patients with typical papillary cancers and 57 patients with oxyphilic follicular cancers treated by the Mayo surgical group during the same time period. Although typical papillary and oxyphilic papillary cancers were comparable with regards to patient age, tumor size and extent, TNM stage, and prognostic score (AGES), there were significant differences. Compared to typical papillary tumors, oxyphilic papillary cancers had fewer neck nodal metastases at primary diagnosis (5% vs 40%, p less than 0.0001), were more often DNA non-diploid (71% vs 21%, p less than 0.001), and after 10 postoperative years had higher rates of both tumor recurrence (28% vs 11%, p less than 0.0001) and cause-specific mortality (1.7% vs 4%, p less than 0.0005). In these four important respects the oxyphilic papillary cancers more resembled the oxyphilic follicular cancers. For oxyphilic follicular cancers, the frequency of initial neck nodal metastases was 7% (cf 5%); 83% of the oxyphilic follicular tumors were non-diploid (cf 71%), and at 10 years postoperatively the tumor recurrence and cause-specific mortality rates were 28% and 18%, insignificantly different from 28% and 17% seen with the oxyphilic papillary cancers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413836 TI - Adrenalectomy in primary aldosteronism: a long-term follow-up study in 52 patients. AB - From 1975 to 1989, 52 patients with primary aldosteronism underwent adrenalectomy. There were 16 men and 36 women. The average age was 42.5 years, ranging from 28 years to 70 years. They were all hypertensive, with average pre operative diastolic pressures varying from 105 to 140 mm Hg (median 117 mm Hg). The subjective symptoms most frequently reported were headache (71%) and asthenia (53%). In all patients except two, serum potassium concentration was 3.3 mEq/L (median 2.7 mEq/L) at the time of diagnosis. Plasma aldosterone concentration was elevated in all patients, 48 +/- 5.3 ng/mL in the recumbent position and 52.6 +/- 6.0 ng/mL in the upright position. The operations carried out were 50 unilateral and 2 bilateral adrenalectomies. In 4 patients a transperitoneal approach was employed and in the remaining 48 patients an extraperitoneal flank incision was used. The histological findings were 47 adenomas (with dimension ranging from 1 to 4.5 cm), unilateral macronodular hyperplasia in 2 patients, an adenoma plus controlateral hyperplasia in 1 patient, bilateral hyperplasia in 1 patient, and unilateral hyperplasia in 1 patient. After long-term follow-up (median 77 months, range 13 to 189 months), 15 patients remained hypertensive (diastolic blood pressure up to 100 mm Hg). In 9 of these patients the hypertensive illness had been present for more than 5 years prior to operation. In the remaining 37 (71%) patients, the arterial pressure returned to normal and in almost half of the patients this result was evident one or two days after operation. PMID- 1413837 TI - Solid cell nests of the thyroid gland: precursor of mucoepidermoid carcinoma? AB - Solid cell nests (SCN) are found within the thyroid parenchyma on routine clinical pathological examinations, but their histogenesis and clinical significance are still obscure. From November 1987 to May 1991, a total of 3,260 patients underwent thyroid surgery at Ito Hospital and SCN were noted in 42 (1.3%) patients. Serial sections of the specimens from these patients were studied morphologically and immunohistochemically. The location and growth pattern of SCN within the thyroid parenchyma were distinct from those of hyperplastic C-cells. SCN were located in the isthmus lobe in 1 patient and even in the pyramidal lobe in 3 patients. In another patient neoplastic proliferation of SCN was observed. Immunohistochemically, SCN were negative for neuron-specific enolase, chromogranin A, and S-100 protein. These findings strongly suggest that SCN are of endodermal origin and that they may be closely related to mucoepidermoid carcinoma of the thyroid gland. PMID- 1413838 TI - Retrospective analysis of prognostic factors affecting the thyroid functional status after subtotal thyroidectomy for Graves' disease. AB - To determine the factors causing thyroid dysfunction after surgery for Graves' disease, we studied 321 patients who underwent subtotal thyroidectomy during the 7-year period from 1981 to 1987. Thyroid functional status was evaluated biochemically and the patients were divided into four categories: recurrent hyperthyroidism, euthyroidism, latent hypothyroidism, and hypothyroidism. The following factors were analyzed: sex, age at onset of the disease, indication for surgery, serum titer of antimicrosomal hemagglutination antibody (MCHA), weight of resected thyroid tissue, size of remnant thyroid relative to body surface area, pathological findings of lymphoid follicles, and lymphocytic infiltration in the thyroid tissue. Probabilities of failure (recurrent hyperthyroidism and hypothyroidism) were estimated by the Kaplan-Meier method. Prognostic factors for failure were identified by using Cox's proportional hazards model. The incidence of hyperthyroidism and hypothyroidism 5 years after subtotal thyroidectomy was 16.2% and 9.6%, respectively. Significant factors for hyperthyroidism were relatively large thyroid remnant, high serum titer of MCHA (greater than or equal to 1:3200), and age at onset of the disease less than 20 years. The significant factor for hypothyroidism was severe lymphocytic infiltration. The level of postoperative thyroid stimulating hormone (TSH)-binding inhibition immunoglobulins (TBII) in patients with recurrence was significantly higher than in patients in remission. It is reasonable to determine the amount of remnant thyroid tissue in relation to patient body surface area. Although subtotal thyroidectomy can induce immunological remission by reduction of antigen, if the remission disappears, that is if TBII increases, recurrence of hyperthyroidism may develop even in patients without the unfavorable factors. PMID- 1413839 TI - Serum chromogranin A in the diagnosis and follow-up of neuroendocrine tumors of the gastroenteropancreatic tract. AB - Hormonally active neuroendocrine tumors may easily be diagnosed by elevated serum levels of their specific peptides and hormonal products, but there are no reliable markers for neuroendocrine tumors without hormonal activity. Chromogranin A (CgA), a secretory protein of neuroendocrine cells, has recently been characterized as a valuable tissue marker in hormonally active and non functioning neuroendocrine tumors. This study analyzes the role of CgA as a serum marker for different neuroendocrine tumors. Thirty-three patients with neuroendocrine tumors of the stomach (n = 7), the ileum (n = 18), and the pancreas (n = 8) were investigated. Serum CgA levels were analyzed by radioimmunoassay at the time of diagnosis and during follow-up under different therapeutic regimens. Serum CgA was elevated in 30 (91%) patients. Mean CgA serum levels varied with tumor location (pancreas: 7068 +/- 3008 ng/ml, ileum: 5381 +/- 1740 ng/ml, stomach: 529 +/- 179 ng/ml, x +/- SEM ng/ml) but did not differ between functioning and non-functioning tumors. Eight of 10 patients treated with either somatostatin or interferon-alpha showed changes of CgA concentrations corresponding to tumor growth. We conclude that CgA is a useful broad-spectrum tumor marker in gastroenteropancreatic neuroendocrine tumors. Its determination is especially recommended in tumors without hormonal activity. PMID- 1413840 TI - The incidence of bilateral well-differentiated thyroid cancer found at completion thyroidectomy. AB - The purpose of this study was to evaluate the surgical outcome of completion thyroidectomy in patients with presumed unilateral well-differentiated thyroid cancer (WDTC). The medical records of all patients having had unilateral thyroid lobectomy for WDTC, who subsequently underwent completion thyroidectomy, were reviewed. From 1980 to 1991, 60 patients with WDTC underwent completion thyroidectomy. Forty-seven patients had presumed unilateral WDTC, with no evidence of residual disease prior to their completion thyroidectomy. Twenty-five (53%) of these patients were found to have residual neoplastic disease in the neck. In 20 (43%) of 47 patients, a focus of cancer was found in the remaining thyroid lobe and in 5 additional patients no cancer was found in the contralateral lobe, however, unsuspected nodal disease was found. The remaining 13 of the 60 patients presented with either regional recurrence (n = 12) or distant metastases (n = 1) at the time of their completion thyroidectomy. All (92%) but 1 of these 13 patients had cancer in the remaining thyroid lobe. Multifocal disease in the primary lobe was associated with bilateral thyroid cancer (p less than 0.01). Complications were infrequent; transient hypocalcemia occurred in 5 (8%) patients, permanent hypoparathyroidism occurred in 1 (1.7%) patient, and transient recurrent laryngeal nerve palsy occurred in 3 (5%) patients. Residual WDTC was found in 37 (62%) of 60 patients undergoing completion thyroidectomy. Multifocal disease in the primary resected lobe was associated with a high incidence of contralateral thyroid cancer. Completion thyroidectomy is a safe procedure and may prevent the development of regional recurrence by eliminating an unsuspected focus of cancer. PMID- 1413841 TI - Prognostic factors in parathyroid cancer: a review of 95 cases. AB - The clinical course, histopathology, and tumor DNA distribution patterns were analyzed in 95 patients with parathyroid cancer. The median follow-up was 6 years (range 1-25 years). Eighteen patients received a benign diagnosis at their first operation. The initial procedure was tumor resection in 42 patients and tumor resection plus partial or total thyroidectomy in 40 patients. Forty patients developed recurrent disease and 36 patients underwent 1 to 9 re-operations. Cervical recurrence and lung metastases were most commonly encountered. The median time from the first operation to recurrence was 33 months (range 1-228 month). Twenty-one patients died of parathyroid cancer a median of 28 months following discovery of their first recurrence. The histopathological reevaluation confirmed unequivocal parathyroid cancer, i.e., infiltration and/or metastases, in 41 cases. Fifty-four cases lacked these criteria but showed various forms of atypia. Image cytometry demonstrated tumor aneuploidy in 26 of 39 cases with definite cancer by histological criteria, compared to the 13 of the 52 with equivocal histological diagnosis. Twelve patients with aneuploid tumors and 7 patients with euploid tumors died of parathyroid cancer. In a multivariate analysis, patients treated with extensive surgery, i.e., tumor resection and unilateral or bilateral thyroidectomy, had a longer survival and a longer relapse free period. Other factors of importance for survival were age and histopathology. Histopathology and an aberrant nuclear DNA content were important factors for the time to recurrence. We conclude that histopathology alone is unable to confirm a cancer diagnosis in the absence of infiltration and/or metastases. Because recurrence may occur late, patients should be followed closely. Even repeated surgical interventions have proven beneficial. PMID- 1413842 TI - Long-term effects of parathyroidectomy for primary hyperparathyroidism on arterial hypertension. AB - The prevalence of arterial hypertension in primary hyperparathyroidism (PHPT) is higher than in the general population. With the aim of determining the evolution of hypertension associated with PHPT, we analyzed a group of 56 patients followed for a mean of 60 months (range 10-101 months) after successful parathyroidectomy for PHPT. The study group consisted of 16 men and 40 women. The mean age was 49 +/- 12 years (range 18-73 years). None of the patients had renal impairment. Two hypertensive patients died during the follow-up from complications related to their hypertension. Twelve (21.8%) patients were hypertensive before parathyroid surgery (systolic greater than 160 mmHg and/or diastolic greater than 90 mmHg). Pre-operative midregion serum parathyroid hormone concentration was higher in the hypertensive patients than in normotensive patients (2.7 +/- 2.4 vs 0.82 +/- 0.4 mu iEq/l, p = 0.018). Pre-operative creatinine clearance was lower in the hypertensive patients than in normotensive patients (65.4 +/- 27.5 vs 86.7 +/- 26 ml/min, p = 0.002). There were no significant differences between normotensive and hypertensive patients in age, sex, body weight, clinical manifestations, weight of parathyroid tissue removed, and calcium metabolism, or in plasma concentrations of magnesium, uric acid, cholesterol, proteins, or albumin. During follow-up, none of the patients with pre-operative hypertension became normotensive, whereas 32% of the patients who were normotensive preoperatively developed clinical hypertension. The global prevalence of postoperative hypertension was thus 48%. The patients that developed hypertension after parathyroidectomy were followed for a longer period than the normotensive patients (76 +/- 17 vs 53 +/- 10 months, p = 0.005), had a lower postoperative creatinine clearance (74 +/- 28 vs 90 +/- 25 mg/min, p = 0.07), and higher cholesterol levels (6.2 +/- 1.5 vs 5.5 +/- 0.9 mmol/L, p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413843 TI - Single and multigland disease in primary hyperparathyroidism: clinical follow-up, histopathology, and flow cytometric DNA analysis. AB - Two-hundred seventy-four patients with primary hyperparathyroidism had selective removal of enlarged parathyroid glands. Biopsies were taken from all parathyroid glands. Normal-size glands were not resected irrespective of their histological appearance. After a mean follow-up of 13.5 years the rates of persistent and recurrent hyperparathyroidism were, respectively, 3.6% and 0.7%. Transient and permanent hypoparathyroidism occurred in 24% and 2.5% of the patients. The microscopic appearance of enlarged glands and of biopsies taken from normal-size glands were reviewed by two pathologists. Normal parathyroid glands were distinguished from abnormal glands fairly accurately (sensitivity 93%, specificity 80%). Microscopic classification of abnormal parathyroid glands as adenomas or hyperplastic glands correlated poorly with the gross classification as single or multigland disease. Flow cytometric DNA analysis of paraffin embedded parathyroid tissue showed significant differences for DNA index, % S phase and % G2M (p less than 0.001). Differentiating single from multigland disease by means of DNA analysis was not possible. In conclusion, removal of only enlarged parathyroid glands results in acceptable rates of persistent and recurrent hyperparathyroidism. Biopsies should only be taken sparingly to prevent transient and permanent hypoparathyroidism. Microscopic examination and flow cytometric DNA analysis can differentiate normal from abnormal parathyroid glands but are unable to differentiate abnormal glands into single or multigland disease. PMID- 1413844 TI - The value of measurement of ras oncogenes and nuclear DNA analysis in the diagnosis of Hurthle cell tumors of the thyroid. AB - Hurthle cell tumors (HCT) remain difficult to treat because some which appear non malignant on light microscopy later metastasize. In order to improve diagnostic accuracy, the value of ras mutations and nuclear DNA analysis was determined in 65 patients with HCT. Rapid nuclear DNA cytometry (MicroTICAS system) was performed. Mutations of H-ras, K-ras, and N-ras genes were analyzed by oligonucleotide probe hybridizations to polymerase chain reaction (PCR) amplified DNA. HCT were classified by light microscopy as benign (n = 22), intermediate (n = 30), and malignant (n = 13). After a mean follow-up of 7 years, 1 (4.5%) of 22 benign tumors and 4 (13%) of 30 intermediate tumors had metastasized, leading to tumor death in 3 of these 5 patients. Six of the 13 cancers diagnosed by light microscopy also resulted in tumor-related deaths. Aneuploidy was found in 83% of all Hurthle cell cancers, including 3 (60%) of the 5 cancers not diagnosed microscopically. However, 49% of non-malignant HCT also demonstrated aneuploidy. A nuclear area of less than 55 square microns was found in 83% of all Hurthle cell cancers and in 100% of those cancers not diagnosed by light microscopy. However, 47% of non-malignant HCT also demonstrated a "small" nuclear area. Aneuploidy correctly identified 8 of 9 cancers that resulted in tumor death and each of 3 other tumors that developed metastases. However, 1 patient with a diploid tumor died of metastatic cancer. A nuclear area of less than 55 square microns identified each cancer that resulted in a tumor death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413846 TI - The role of epinephrine, norepinephrine, and dopamine in blood pressure disturbances in patients with pheochromocytoma. AB - Fifty-six patients with pheochromocytoma underwent surgery during the 9-year period from 1981 to 1990. These patients were divided into two groups according to whether the dominant plasma concentration was of epinephrine or norepinephrine. Plasma levels of the catecholamines were stratified into three grades at 5 and 10 times the normal upper limit. Pre-operative disturbances of blood pressure, sustained or paroxysmal, and normal blood pressure were highly correlated with the dominantly secreted catecholamine and its plasma concentration. Thirteen patients with high plasma norepinephrine levels (greater than or equal to 10 times normal) had sustained hypertension while 18 patients with moderate to high plasma epinephrine levels (greater than or equal to 5 times normal) had paroxysmal hypertension. In the majority of normotensive patients (12 of 14), plasma catecholamine levels were less than 10 times the upper normal limit. Urinary excretion of dopamine and size of the tumor were analyzed according to these patient groups. In the norepinephrine dominant group, urinary dopamine excretion tended to be proportional to the plasma epinephrine levels and when the patients were normotensive, urinary dopamine excretion decreased. In norepinephrine-secreting patients, urinary dopamine tended to be inversely correlated with the plasma norepinephrine level; however dopamine did not prevent the hypertensive action of norepinephrine. Tumor size showed no correlation with the plasma levels of catecholamine in the moderate to high plasma catecholamine groups. We conclude that the plasma catecholamine type and its level are the most important factors in determining the patterns of blood pressure disturbances of patients with pheochromocytoma. PMID- 1413845 TI - Survival rates and prognostic factors in adrenocortical carcinoma. AB - In the last 12 years, 41 patients with adrenocortical carcinoma were operated on at Cochin Hospital. There were 29 females and 12 males having an average age of 42 +/- 17 years. Seven of them underwent repeat operation for local recurrence after an average interval of 22 months. Eighty per cent of the tumors had secretory activity while 20% did not. Adrenalectomy and lymphadenectomy were performed on all patients. Thirteen (32%) patients underwent extensive resection because of invasive cancer. The same procedure was performed on 7 patients undergoing re-operation. Operative mortality was 4% (2 of 48 patients). Twenty four patients died of cancer with an average survival time of 22 months (range 2 86 months) and 15 (37%) patients were still alive, 4 of them with metastases, with an average survival time of 51 months. Curative resection for the 31 patients with local (n = 21) or regional disease (n = 10) allowed a 5 year actuarial survival rate of 45%. The 5 year actuarial survival rate for patients undergoing repeat surgery was 33%. Only 1 of the 10 patients with metastases, and who had an impressive response to OP'DDD, was alive 2 years after the operation. The other 9 patients died within 3-4 months after operation. We found that neither patient characteristics or tumor characteristics were of significant prognostic value. There was no overall prolongation of survival in patients receiving OP'DDD. However 4 patients with metastases occurring in the course of their disease experienced an impressive response with OP'DDD and a relatively long survival. PMID- 1413847 TI - Surgery for hyperthyroidism: hemithyroidectomy plus contralateral resection or bilateral resection? A prospective randomized study of postoperative complications and long-term results. AB - Fifty consecutive patients undergoing surgical treatment for hyperthyroidism were randomized to have either bilateral subtotal resection (n = 23) or hemithyroidectomy plus contralateral resection (n = 27). No significant differences in operating time or intra-operative bleeding were found. No postoperative bleeding and no temporary or persistent recurrent laryngeal nerve paralysis occurred. Four patients who underwent bilateral resection and 2 patients who had hemithyroidectomy resection needed temporary calcium supplementation, and the serum calcium concentrations were slightly lower during the first few postoperative days in the patient undergoing hemithyroidectomy/resection. No persistent hypocalcemia occurred in either of the groups. At follow-up 3-4 years (mean 3.6 years) postoperatively, 1 patient in the bilateral resection group developed recurrent hyperthyroidism; no patients in the hemithyroidectomy/resection group developed recurrent hyperthyroidism. Twelve (44%) patients in the hemithyroidectomy/resection group and 8 (35%) patients in the bilateral resection group needed thyroxine supplementation because of a rise in thyroid stimulating hormone concentration combined with clinical signs of hypothyroidism that developed during follow-up. Hyperthyroidism can be treated by hemithyroidectomy plus contralateral resection without increasing the risk of complications. The results also suggest that when using this method, a slightly larger thyroid remnant should be left to avoid an increase in the incidence of hypothyroidism postoperatively. PMID- 1413848 TI - Primary hyperparathyroidism in Austria: results of an 8-year prospective study. AB - Serum calcium determinations in 45,217 hospitalized patients during an 8 year period revealed sustained hypercalcemia in 124 (0.3%) patients. Further clinical and biochemical investigations established primary hyperparathyroidism (PHP) in at least 40 (32%) patients, an incidence of PHP of 89.6 +/- 41.5 per 100,000 patients per year. The incidence of PHP in males and females was 31.5 and 124.2 per 100,000, respectively. The highest incidence was found in females greater than 66 years of age (268.8 per 100,000). Nineteen (48%) patients showed classical symptoms of PHP, 14 (35%) patients were minimally symptomatic, and 7 (17%) patients were asymptomatic. The incidence and symptomatology of PHP in Austria is nearly the same as in other countries. Because of the multiple actions of parathyroid hormone in the body, PHP can cause debilitating symptoms but too often it remains undiagnosed clinically. Routine calcium determinations are very important and PHP must always be considered in the differential diagnosis, especially in minimally symptomatic patients. PMID- 1413849 TI - Percutaneous ethanol injection treatment of autonomously functioning single thyroid nodules: optimization of treatment and short term outcome. AB - Twenty-five patients with solitary autonomous thyroid nodules (15 nontoxic, 10 toxic) received percutaneous ethanol injection treatment (PEIT) under sonographic guidance in 4-7 sessions (1-2 weekly). To test different doses, smaller nodules (volume less than 15 mL) were given 0.75-2.8 mL ethanol/mL nodular tissue while larger nodules received 0.5-1 mL/mL. Except for 1 patient who developed hyperpyrexia, no relevant adverse effects were observed. A slight, asymptomatic increase in serum thyroid hormone levels was observed in both groups during the treatment. Three months after treatment, a biochemical and clinical remission of hyperthyroidism was observed in 8 of 10 patients with toxic nodules. A significant increase of TSH level was seen in both groups (p less than 0.01). Significant shrinkage of volume (p less than 0.001) as well as structural alterations of nodules were consistently recorded at sonography. A linear relationship (r = 0.98; p less than 0.0001) between pretreatment volume and volume reduction was found both for large and small nodules, thus suggesting that even limited ethanol doses may be therapeutically effective. A recovery of extranodular parenchyma activity at scintiscan occurred in 16 (64%) of 25 patients. These data confirm that PEIT is effective in obtaining functional ablation and in inducing remission of hyperthyroidism. Adverse effects are infrequent. In spite of the small patient sample, a 0.5-1 mL ethanol dose per each mL of tissue appears as effective as larger doses and seems appropriate for treatment. PMID- 1413851 TI - Comment on the treatment strategy for cecal diverticulitis as proposed by Schmit and coworkers. PMID- 1413852 TI - A template for health information. AB - The Template for Health Information is a software package for microcomputers developed by the National Task Force on Health Information of Statistics Canada. The Template software provides a conceptual framework for the collection, analysis and utilization of health information for policy planning and management uses. This framework involves interactions between a population of individuals, their external environment, and sets of potential health-affecting interventions. The Template is seen as a pedagogical device for incorporating the many perspectives of different health constituencies. A floppy diskette is provided with the article to demonstrate the potential of the Template. PMID- 1413850 TI - Primary hyperparathyroidism in younger and older patients: symptoms and outcome of surgery. AB - Two-hundred and fifty patients undergoing initial exploration for primary hyperparathyroidism were analyzed for differences in clinical presentation, biochemical status, pathology, and outcome of surgery. In patients less than 60 years of age (younger patients, n = 119) the most common preoperative symptoms and signs were fatigue (40.3%), bone pain (33.6%), renal stones (31.0%), hypertension (27.7%), and psychiatric illness (27.7%). In patients greater than or equal to 60 years of age (older patients, n = 131) the most frequent symptoms and signs were hypertension (46.6%), fatigue (35.1%), bone pain (30.5%), muscle weakness (28.2%), and joint pain (22.9%). Renal stones were 2.6 times more common (p less than 0.001, chi 2) in younger patients and hypertension 1.7 times more common (p less than 0.05, chi 2) in older patients. There was no significant difference in the preoperative and postoperative laboratory values typically associated with primary hyperparathyroidism. Double adenomas were more common in older (9.2%) than in younger patients (2.5%, p less than 0.05, chi 2). Surgical cure was obtained in 98.8% of patients, and after parathyroidectomy 83% of the younger and 82% of the older patients experienced substantial relief of pre operative symptoms. Specific questioning revealed most patients to be symptomatic and older patients appear to receive the same clinical and metabolic benefits from parathyroidectomy as younger patients. PMID- 1413853 TI - Trends in cancer mortality sex ratios in Europe, 1950-1989. AB - A study was carried out to analyse trends in cancer mortality sex differentials. This study compared age-standardized sex ratio values for mortality from 18 cancers (or groups of cancers), and total cancer mortality over the period 1950 1989 in 24 European countries, for 4 age groups (all ages, 20-44 years, 45-64 years, and 65 years and over). For lung cancer and other tobacco-related neoplasms, appreciable rises in sex ratio values were observed until the late 1970s, particularly in Southern and Eastern Europe, before levelling off in recent years, particularly among the younger age groups. In the late 1980s, the range of variation in overall age-standardized sex ratios for lung cancer was between 2 and 3 in the United Kingdom and in Nordic countries, and around or over 10 in Southern Europe. In young adults, the decline in sex ratio values observed in Denmark and Sweden (unity), and in other Nordic countries and in the United Kingdom (around or below 2) reflects a levelling of lung cancer in young males and an increase in young females. This clearly indicates that young women are a priority target group for smoking control interventions in Europe. Appreciable cohort effects were also observed for stomach cancer: rises in sex ratio values were greater in, or restricted to, middle- and older age groups, whereas in the young there was some tendency towards a levelling in sex differentials. The overall sex ratio values for stomach cancer were around 2 in most areas of Europe in the late 1980s. For intestinal cancer, sex ratio values showed some tendency to rise, reaching a level of 1.3-1.7 in the late 1980s; steady rises were also registered in sex ratio values for melanoma (skin cancer), reaching 1.5-1.8 in the late 1980s in most countries. These upward trends which were minor or inconsistent at younger ages in several countries became progressively stronger with advancing age. Sex ratio values were below unity for cancers of the gallbladder and the thyroid. Sex ratio values tended to rise also for leukaemia (from 1.2-1.5 to 1.5-1.7), but showed no noticeable trend for lymphomas or myeloma. The overall sex ratio values for total cancer mortality in the 1950s were between 1.2 and 1.4 in most European countries. Thereafter, they rose appreciably in several countries, reaching 1.9 in Czechoslovakia, Italy and Poland, and 2.3 in France.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1413854 TI - The evolving demography of aging in the United States of American and the former USSR. AB - In the United States of America and in the republics of the former USSR, the elderly (persons aged 60 and over) will comprise the same proportion of their respective societies by the year 2000, namely 17%. In both countries, this population subgroup is growing at a faster rate than the rest of the population and living longer, although there are now more differences than similarities between the two countries in respect of the elderly, as summarized below. Similarities. In both countries today, the age group 50 years and over represents 26% of the total population, and by the year 2000 it is expected that 17% of the population will be 60 years and over. Diseases of the circulatory system and neoplasms are the major causes of death in both countries. Life expectancy beyond retirement age (i.e. the number of years a person is expected to live after having retired) is about the same in both, but this is due to the statistical fact that in the former USSR women are expected to have an extra year of life expectancy compared to their United States counterparts, while men are expected to live 2.5 years less beyond retirement than their United States counterparts. Differences. Mortality rates in the former USSR are higher than those in the United States. Life expectancy for men in the former USSR is 6.5 years below the figure for United States males. By age 65, the differences are 2.7 years for women and 2.4 years for men. Today, the proportion of the population having reached retirement age is larger in the former USSR than in the United States (17% vs 15%) because of lower retirement age in the former USSR. By the year 2000, these figures are expected to be 19% and 25%, respectively. Men make up 27% of the pension-age population in the former USSR against 41% in the United States. Life expectancy at birth could increase by 4 years for men in the former USSR if they had the same mortality rates from diseases of the circulatory and respiratory systems as their United States counterparts. Similarly, women in the former USSR would gain 4 years of life from these two causes alone. Older women are more likely to be married in the United States than in the former USSR, and this difference increases with age: at age 65, 25% of the former USSR's women are married versus 41% in the United States. PMID- 1413855 TI - Analysis of mortality data from the former USSR: age-period-cohort analysis. AB - The objective of this article is to review research on age-period-cohort (APC) analysis of mortality and to trace the effects of contemporary and historical factors on mortality change in the former USSR. Several events in USSR history have exerted a lasting influence on its people. These influences may be captured by an APC model in which the period effects measure the impact of contemporary factors and the cohort effects the past history of individuals which cannot be attributed to age or stage in the life cycle. APC models are extensively applied in the study of mortality. This article presents the statistical theory of the APC models and shows that they belong to the family of generalized linear models. The parameters of the APC model may therefore be estimated by any package of loglinear analysis that allows for hybrid loglinear models. PMID- 1413857 TI - Economic aspects of health. AB - This study described in this article was undertaken to assess the possibility of getting a general picture of the public health situation to be used in such economically oriented models as cost-benefit, cost-effectiveness and cost utility. Problems of data bases encountered in this assessment of various republics, regions and administrative entities are also considered. New mathematicodemographic statistical models and a family of potential factographic automated information reference systems (FAIRS) based on these models and designed to be utilized in projects, programmes and regional systems of public health are analysed. PMID- 1413856 TI - Some problems of medicodemographic development in the former USSR. AB - The republics of the former USSR show great diversity in life expectancy, and in morbidity and disability prevalence rates. The diversity in life expectancy is strongly influenced by the different age, sex and cause-specific mortality rates obtaining in each republic. These in turn are determined by environmental, climatic and topographic features, as well as by social and economic development and lifestyle, including nutritional habits. In addition, large urban and rural differences are noted which may be partly accounted for by the restricted access to and low quality of health care in rural areas. Mortality, morbidity and disability rates have also shown unfavourable trends between 1965 and 1989 in many of the republics. The authors suggest further research to elucidate observed mortality, morbidity and disability differentials and trends, viz. analyses using finer breakdown of the population; examination of risk-factor-pattern data for mortality and morbidity by social groups and regions; the collection of data on health and demographic problems of ethnic minorities; greater use of socioeconomic development indicators at the regional level; surveys of individual opinions on perceived health, health requirements and quality of care received; and the development of appropriate medicodemographic models for analytic and forecasting purposes. PMID- 1413858 TI - Data needs for health policy in an aging population (including a survey of data available in the United States of America). AB - The development of a coordinated, systematic and responsive data base is essential for governments to make informed decisions for policy development and planning, to assess the impact of these decisions, and to operate their programmes effectively. One of the most significant challenges is the development of data systems capable of satisfying the multiple needs for data, and providing the data required for evaluating the impact of health programmes, while keeping the respondent burden reasonable. The United States of America is fortunate in having well-developed systems of data collection by national surveys for demographic, social and economic characteristics of the population, morbidity and mortality, health expenditures, and use of health and long-term care services. Current survey and administrative record data sets are described. Policy issues in health care for aging populations require the use of multiple data sets which may require modification of or addition to existing surveys and administrative records. Recommendations are made for an extension of the data bases already in existence and on the expansion of analytical capacity to address health policy issues for the elderly. PMID- 1413859 TI - An overview of relevant data sources in the former USSR for studies in demographic trends, aging and noncommunicable disease problems. AB - This article provides an overview of health data available in the former USSR. It is not all-inclusive in terms of chronic diseases covered or in details of data collection activities carried out. However, several broad conclusions can be drawn: There is a system of population and mortality data collection which covers the former USSR and which can be disaggregated to smaller administrative areas. The system is being exploited by population specialists, demographers, medical demographers and epidemiologists, both nationally and internationally, both for analytical purposes and as part of health monitoring systems. A national-level data-collection system for morbidity and disability, based on delivery of health services, is in place and is exploited by both health researchers and health planners. The shortcomings of such a health service-based statistical system are well recognized. Further standardization or calibration of measures of total and cause-specific morbidity and disability measures should be examined. A potential calibration tool is the 1988-1993 health examination and interview survey covering a representative (but highly clustered) sample of the former USSR population. The possibilities of greater standardization of measurement procedures used in this survey should also be investigated. In certain disease areas, e.g. cardiovascular diseases, cancer, rheumatic diseases and gerontology, clinical and epidemiological studies involving international collaboration have been carried out. This has resulted in the use of internationally accepted disease definitions, diagnostic procedures, and of clinical and laboratory standardization of demographic, social and biological measurements. Participation in multilateral or bilateral studies should be encouraged in research in disease areas where these types of programmes have not yet been instituted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413860 TI - Epidemiology and aging: how gerontology has changed noncommunicable disease epidemiology in the United States of America. AB - Epidemiology is a continuously evolving discipline that has been greatly enriched by addressing the health problems of the elderly. In the United States of America, this has resulted in a large national data resource of functional and health measures on older populations, heretofore not available. In this article, suggestions are made for research priorities in the next 10 years in the epidemiological study of the elderly. They include: (i) a special emphasis on enhancing analytical methods, particularly for complex longitudinal data; (ii) an effort to understand the impact of the physiochemical environment on older persons, both in the household and workplace setting; (iii) the identification of new ways to determine early life exposures among older persons, so that hypotheses about early influences on aging processes can be tested; and (iv) a general effort to include function status and other geriatric measures as a routine part of the clinical record, so that secondary research on such records can be more conveniently performed. PMID- 1413861 TI - Forecasting health: data needs and implications for model structure. AB - An agenda for analysing data on the health and functioning of the elderly must indicate new types of data to be collected, innovations in data collection strategies and new methods for analysis and forecasting. The required research agenda is broad and will require inputs from investigators in a number of disciplines. The data and methods required will need to be developed in order to reflect national, regional and local variations in the health phenomena under study; they will also have to be responsive to these variations. In the end, however, if the investment is to be most useful, it must be integrated into simulation and forecasting models, the mechanics of which are based on individual level processes and not on the elements of the service system. PMID- 1413862 TI - Resource allocation problems and health services for the elderly. AB - The provision of appropriate health support services for the elderly has increased in importance because of the trend towards aging populations in Europe and other developed regions. Health service resource allocation models and their roles in health service systems, which are also changing to reflect changing needs for the elderly, are discussed in this article. Different types of economic and health care delivery systems are examined, particularly those leading towards decentralization, consumer participation and "deinstitutionalization". A promising resource allocation approach--the "balance-of-care" approach--is described in some detail. This and other potential approaches make it possible to identify areas which hold promise for crossnational research. PMID- 1413863 TI - Health economic issues relevant to countries with aging populations. AB - This article investigates the health economic impacts of aging populations, using scenario techniques and economic systems analysis. Age-related data on hospital utilization and health care expenditure are linked with demographic models for Germany from 1990 to 2040. Findings indicate that the demographic component may not play a major role in determining long-term trends as compared with other, not yet fully elucidated components of utilization and expenditure, both of which are the result of the interplay between supply and demand in health care, and of interactions with the general economy. This acts as a deterrent against the use of simple extrapolations of current indicators (or their trends), but more adequate theoretical economic models are still lacking. PMID- 1413864 TI - Metabolism of pravastatin sodium in isolated rat hepatocytes. I. Glutathione conjugate formation reaction. AB - 1. The metabolic fate of pravastatin sodium (sodium (+)-(3R,5R)-3,5-dihydroxy-7 ((1'S,2'S,6'S,8'S,8'aR)-6'-hydroxy-2'methyl- 8'-[(S)-2"-methylbutyryloxy] 1',2',6',7',8', 8'a-hexahydro-1'-naphthyl) heptanoate) was studied in isolated rat hepatocytes. 2. Two polar metabolites were isolated and identified as a glutathione conjugate and a dihydrodiol. 3. Both metabolites were formed via an epoxide which has been identified as the 4'a beta,5' beta-epoxide on the decalin moiety. 4. Formation of the glutathione conjugate was enzymic, while the dihydrodiol was formed by non-enzymic hydrolysis of the epoxide accompanied by the intramolecular migration of the double bond. PMID- 1413865 TI - Structural determination of the carboxylic acid metabolites of polychlorotrifluoroethylene. AB - 1. Polychlorotrifluoroethylene (PCTFE) is a perhalogenated hydrocarbon which consists mainly of C-6 and C-8 oligomers of chlorotrifluoroethylene (CTFE) end capped with chlorine and referred to as trimer and tetramer, respectively. PCTFE is a hydraulic fluid considered for use in advanced weapon systems. 2. Inhalation studies have shown that PCTFE causes a dose-related hepatotoxicity in rats that is accompanied by proliferation of hepatic peroxisomes and increased liver weight. 3. Carboxylic acid metabolites of PCTFE have been isolated from rats exposed to PCTFE via inhalation. These metabolites, or their formation, may be involved in the toxicity of PCTFE. 4. Trimer carboxylic acids have been isolated from rat urine and identified, and tetramer carboxylic acids have been isolated from rat liver, and identified. 5. Our investigation of trimer and tetramer carboxylic acid metabolites of PCTFE has shown that the terminal carbon bearing two chlorine atoms is the exclusive site of oxidation. No evidence was found indicating oxidation of terminal carbon atoms having one chlorine. PMID- 1413866 TI - The effect of age on inducibility of various types of rat liver cytochrome P-450. AB - 1. The content and specific activities of inducible cytochrome P-450 enzymes were determined in liver microsomes of rats of various ages after maximal induction with phenobarbital, isosafrole of 3-methylcholanthrene, and in untreated animals. 2. With age an increase in liver weight was observed both in untreated rats and in maximally induced ones; the microsomal protein content/g of liver decreased with age in untreated animals but not in induced ones. Total cytochrome P-450 content/mg microsomal protein remained unchanged with age in all experimental groups. 3. Immunologically detectable levels of cytochrome P4501A1/1A2 and 2B1/2B2 remain unchanged with age both in untreated animals and in maximally induced ones. 4. Several cytochrome P-450 activities showed an age-related decrease in untreated animals, but no change with age was observed in the activities of cytochrome P4501A1, 2A2 and 2B1/2B2 in rat liver microsomes. This indicates that ageing affects only the activity of some constitutive forms of cytochrome P-450 in male rats, but not the activity of inducible types of P-450. 5. Although previous results indicated decreased inducibility of the cytochrome P 450 mRNA levels with age, the present study clearly demonstrates that this is not reflected in decreased enzyme levels or activities after maximal induction. From this it is concluded that the decreased mRNA levels might rather be reflected in a decreased rate at which maximal induction can be achieved. PMID- 1413867 TI - Effects of various medium formulations and attachment substrata on the performance of cultured ruminant hepatocytes in biotransformation studies. AB - 1. A procedure for the isolation and primary culture of hepatocytes from goat and cattle is described. Hepatocyte culture performance was monitored for 51 h by measuring viability, cytochrome P-450 maintenance, dealkylation of scoparone and ethylmorphine, and glucuronidation of phenol red. 2. Culture medium composition is discussed in relation to differences between splanchnic blood composition of ruminant and monogastric animal species. Main differences are in glucose and volatile fatty acid concentrations. Modified Williams' E culture medium did not yield higher culture performance than non-modified Williams' E. 3. Coating of culture dishes with either collagen or fibronectin did not improve culture performance. 4. Williams' E, although developed for rodent cells, proves to be a suitable basal medium for ruminant hepatocytes. In this medium, culture quality is high for at least several days. 5. In cultured goat hepatocytes, biotransformation rate for scoparone amounted to 20 nmol/mg protein per h, for ethylmorphine 96 nmol/mg protein per h and for phenol red 2 nmol/mg protein per h. Biotransformation activity in cow hepatocytes is approximately half that in goat hepatocytes. PMID- 1413868 TI - Simplified approach for evaluation of hepatic drug-oxidizing capacity with a simultaneous measurement of caffeine and its primary demethylated metabolites in carbon tetrachloride-intoxicated rats. AB - 1. Prediction of hepatic injury from changes in blood concentrations of caffeine (CA) and its three primary metabolites (theobromine: TB; paraxanthine: PX; theophylline; TP) after CA administration has been studied in carbon tetrachloride (CCl4)-intoxicated rats. 2. The plasma half-life (t1/2) of CA (10 mg/kg, oral) was increased, and total body clearance (CL) decreased, in CCl4 treated rats; the apparent volume of distribution (Vd) was relatively unchanged. 3. The ratios of CA to the three metabolites (TB/CA, PX/CA, TP/CA) were significantly decreased compared to those of controls. 4. There were good correlations between the ratios of TB/CA, PX/CA, and TP/CA and CL of CA (TB/CA; r = 0.944 at 1 h, r = 0.942 at 2 h: PX/CA; r = 0.974 at 1 h, r = 0.923 at 2 h: TP/CA; r = 0.866 at 1 h, r = 0.962 at 2 h). 5. Results indicate that it is possible to evaluate hepatic drug-oxidizing capacity by measuring the ratio of CA to its metabolites, using single blood sampling 1 or 2 h after CA administration in CCl4-intoxicated rats. PMID- 1413869 TI - Pharmacokinetics and efficacy of structurally related spirohydantoin and spirosuccinimide aldose reductase inhibitors. AB - 1. Six potent aldose reductase inhibitors (ARI), three spirohydantoin (I to III) and three spirosuccinimide (IV to VI) compounds, showed similar IC50 activities in vitro for the inhibition of rat lens aldose reductase, but their ED50 values in diabetic rats varied as much as 20-fold in the lens and 50-fold in the sciatic nerve tissue. Pharmacokinetic studies were undertaken to investigate these findings. Structure-pharmacokinetic relationships were studied following i.v. administration to cynomolgus monkeys. 2. The clearance (CL) of each spirosuccinimide ARI was faster (greater than 5 times) than that of the corresponding spirohydantoin compound. In both series the CL values of the C(4) methyl and methoxy analogues were 4-fold greater than those for the unsubstituted compounds, although the CL values of the methoxy and methyl derivatives in the same series were not significantly different. 3. The volumes of distribution (Vss) of the spirohydantoins were about one-half those of the corresponding spirosuccinimides, and the Vss values of the parent compounds of both ARI series did not differ dramatically from those of their methyl and methoxy analogues. 4. All six compounds were eliminated from plasma in a biexponential fashion. The half-lives (lambda 1 and lambda 2) of the spirohydantoin compounds were much longer than those of the corresponding spirosuccinimide compounds, and the unsubstituted compounds had longer half-lives than their methyl and methoxy derivatives. The longest lambda 1 and lambda 2 half-lives were observed for imirestat, while two of the spirosuccinimides had the shortest half-lives. 5. These results indicate that the relationships observed between the in vitro and in vivo activities of the six ARI can be attributed to structurally dependent differences in metabolic clearance. PMID- 1413870 TI - Pharmacokinetics and excretion of phenol red in the channel catfish. AB - 1. Disposition of phenol red was examined in channel catfish (Ictalurus punctatus) after oral or intravascular (i.v.) dosing at 10 mg/kg body weight. 2. Phenol red was not detectable in plasma, urine, or bile after oral administration. 3. After i.v. dosing, plasma concentrations of phenol red were best described by a two-compartment pharmacokinetic model with distribution and elimination half-lives of 2.3 and 21 min, respectively. The apparent volume of distribution at steady state (Vss) was 225 ml/kg and total body clearance (Clb) was 658 ml/h per kg. Plasma protein binding was 19%. 4. Biliary excretion was the primary route of elimination of phenol red; in 24 h, 55% of the i.v. dose was excreted in bile compared with 24% in urine. No metabolites were detected in these fluids. 5. The use of anaesthesia during dosing had no effect on the quantitative excretion of phenol red by renal or biliary routes. PMID- 1413871 TI - Diazepam metabolism by rat and human liver in vitro: inhibition by mephenytoin. AB - 1. Diazepam metabolism and its association with mephenytoin hydroxylase were studied in vitro using human and rat livers. 2. Enzyme kinetic parameters were obtained for the formation of p-hydroxydiazepam (p-hydroxy-DZP), N desmethyldiazepam (NDZ), and temazepam (TMZ) from diazepam (DZP) in rat liver fractions. The Km values for formation in rat of p-hydroxy-DZP, NDZ and TMZ were 14 +/- 3 (SEM) microM, 44 +/- 4 and 63 +/- 8, respectively; clearance values calculated from Vmax/Km were 5.7, 3.2 and 4.9 ml/g per min, respectively. 3. Mephenytoin (MP) competitively inhibited, in rat liver, the formation of NDZ, but not the formation of p-hydroxy-DZP or TMZ; in human liver neither NDZ nor TMZ formation was inhibited by MP. 4. In seven different human livers the formation of p-hydroxy-DZP represented a minor pathway compared to the formation of NDZ and TMZ. PMID- 1413872 TI - The metabolism of muzigadial by microorganisms. AB - 1. A total of 114 microorganisms were evaluated for their ability to metabolize the antifungal drimane sesquiterpene, muzigadial. 2. Cryptococcus neoformans was found to convert muzigadial to one major metabolite, identified as a hemiacetal. 3. Streptomyces platensis produced three metabolites: the hemiacetal, its corresponding lactone, and the epoxide of the hemiacetal. 4. Streptomyces spectabilis produced the hemiacetal as well as the epoxy hemiacetal. 5. The proposed structures of all of the metabolites were based on comparisons of the spectroscopic data (1H- and 13C-n.m.r. spectra and mass spectra) between the metabolites and the parent compound. 6. Antimicrobial evaluation of the microbial metabolites indicate that metabolism decreases antifungal activity. PMID- 1413873 TI - Pharmacokinetics of ticlopidine during chronic oral administration to healthy volunteers and its effects on antipyrine pharmacokinetics. AB - 1. The pharmacokinetics of ticlopidine, a novel antithrombotic agent, have been investigated in 10 healthy volunteers dosed orally with the drug (250 mg 12 hourly for 21 days), to determine the basic pharmacokinetic parameters in humans, to investigate its accumulation during repeated administration, and to assess its effects on hepatic drug-metabolizing enzymes. 2. After the first dose, peak plasma concentrations (median 0.31, range 0.08-0.80 mg/l) were generally found at 2 h. The levels decreased rapidly to a median concentration of 0.087 mg/l by 4 h then declined to 0.022 (range less than 0.005-0.128) mg/l at 12 h after administration, with apparent half-lives of approx. 4 h. The median AUC value for this first dosage interval (AUC tau) was 0.97 (range 0.41-3.49) mg h l-1. 3. Pre dose plasma concentrations indicated that steady state was reached after 5-10 days, and then remained essentially unchanged through to the end of the study. From 30 h after the final dose, drug levels declined exponentially with a median half-life of 28.8 (range less than or equal to 20-50) h. 4. Following the final dose, the median peak concentration and AUC tau were 0.99 (range 0.22-2.12) mg/l and 4.06 (range 0.90-15.2) mg h l-1 respectively. Based on AUC values, the mean accumulation factor +/- SD was 3.73 +/- 1.14. 5. The metabolic status of subjects was assessed by administration of single doses of antipyrine (700 mg orally) 7 days before the first dose of ticlopidine and 2 days after the final dose. Treatment with ticlopidine decreased antipyrine clearance, demonstrating that it inhibited drug-metabolizing enzymes. Significant correlations (r2 = 0.84, p less than 0.01) were found between the AUC values for ticlopidine and antipyrine, indicating that the interindividual variation in the pharmacokinetics of ticlopidine are explained by differences in metabolic clearance. PMID- 1413874 TI - Effects of arsenite on hepatic mixed-function oxidase activity in rats. AB - 1. Injection of arsenite (As3+) to control rats results in losses of total hepatic cytochrome P-450 and significant decreases of ethoxycoumarin O-deethylase (ECOD) and ethoxyresorufin O-deethylase (EROD) activities. However, As3+ appears to decrease the activity of these enzymes differentially, with EROD showing greater sensitivity than ECOD. 2. Injection of As3+ to rats treated with phenobarbital and isosafrole significantly decreases the total content of hepatic cytochrome P-450 and various mixed function oxidase (MFO) activities, with the exception of ECOD which appears to be insensitive to As3+. 3. 3 Methylcholanthrene administration apparently protects against the effects of As3+ on the cytochrome P-450 system, since total content of the cytochrome P-450 and various MFO activities were all insensitive to this treatment. PMID- 1413876 TI - Linoleate-dependent co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8 dihydrodiol by rat cytosolic lipoxygenase. AB - 1. Co-oxygenation of 14C-labelled benzo(a)pyrene and benzo(a)pyrene-7,8 dihydrodiol was studied in rat lung cytosol, using linoleic acid as a co substrate. Covalently bound and soluble metabolites were quantified by radiometry and h.p.l.c., respectively. 2. The co-oxygenation resulted in the production of reactive metabolites capable of protein binding as well as a series of soluble derivatives. 3. Co-oxygenation of benzo(a)pyrene yielded primarily a significant amount of benzo(a)pyrene-6,12-dione while benzo(a)pyrene-7,8-dihydrodiol led to a significant amount of benzo(a)pyrene-trans-anti-tetrol. 4. Their production was abolished by addition of 25 microM of the lipoxygenase inhibitor and antioxidant NDGA. 5. It is postulated that the linoleic acid peroxyl radicals, formed by rat lung lipoxygenase, initiate the one-electron oxidation of benzo(a)pyrene to its quinones, and epoxidation of benzo(a)pyrene-7,8-diol to the ultimate carcinogenic benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide. PMID- 1413877 TI - Hepatic mixed-function oxidases of ferret. AB - 1. Ferret liver mixed-function oxidase enzymes have been quantified using a variety of substrates and the activities have been compared with those found in rat liver. 2. Ferret liver total cytochrome P-450 is only 30% of that of rat liver and exhibits higher 7-ethoxyresorufin O-deethylase (EROD) activity, and lower lauric acid hydroxylase activity than rat liver; other mixed-function oxidases are at similar levels of activity in both species. 3. Induction with 3 methylcholanthrene (MC), similar to MC-induction in rat, increases the total P 450 of ferret liver by 140%, but does not increase P-450 reductase or microsomal protein. EROD specific activity (pmol/min per mg protein) is increased 20-fold by MC treatment. 4. Turnover number of EROD for control liver microsomes of ferret, hamster, mouse, guinea pig and rat were 460, 69, 44, 36 and 35 pmol/min per nmol P-450, respectively, indicating the much higher value for ferret than for any of the rodent species studied. 5. Ferret liver EROD activity is inhibited by the P4501A1 inhibitor, alpha-naphthoflavone. Use of monospecific antibodies in ELISA, Western blot and enzyme-inhibition techniques has shown that EROD activity in ferret liver is attributable to two enzyme proteins orthologous with rat liver cytochromes P4501A1 and 1A2, with the former predominating. MC induces both P4501A enzyme proteins in ferret liver, as in rat liver, with P4501A1 activity predominating. PMID- 1413875 TI - The interaction of phosphine with haemoglobin and erythrocytes. AB - 1. Phosphine progressively converts oxyhaemoglobin to methaemoglobin and hemichrome species, with the product formed being time- and concentration dependent. 2. The reaction of phosphine with oxyhaemoglobin leads to the formation of phosphite and phosphate. 3. Incubation of rat erythrocytes with various concentrations of phosphine results in the progressive uptake of phosphine by the erythrocytes in a temperature-dependent first-order process. 4. Uptake of phosphine by erythrocytes causes crenation, but conversion of oxyhaemoglobin to methaemoglobin and hemichrome could not be demonstrated. PMID- 1413878 TI - Metabolism of 2,6-dinitro[3-3H]toluene by human and rat liver microsomal and cytosolic fractions. AB - 1. 2,6-Dinitrotoluene (2,6-DNT) metabolism by human liver and male Fischer F344 rat liver subcellular fractions under aerobic (100% oxygen) and anaerobic (100% nitrogen) incubation conditions was examined. Under aerobic conditions the major 2,6-DNT metabolite formed by hepatic microsomes was 2,6-dinitrobenzyl alcohol (2,6-DNBalc); under anaerobic conditions 2-amino-6-nitrotoluene (2Am6NT) was the major metabolite. 2. Rates of 2,6-DNBalc formation by human and rat liver microsomes under aerobic conditions were 247 and 132 pmol/min per mg protein, respectively. Rates of 2Am6NT formation by human and rat liver microsomes under anaerobic conditions were 292 and 285 pmol/min per mg protein, respectively. Anaerobic reduction of 2,6-DNT to 2Am6NT by rat and human liver microsomes was inhibited by carbon monoxide and metyrapone, which indicates that microsomal metabolism of 2,6-DNT to 2Am6NT is mediated by cytochrome P-450. 3. Liver cytosolic fractions also metabolized 2,6-DNT to 2Am6NT under anaerobic conditions. Formation of 2Am6NT by human and rat liver cytosols was supported by hypoxanthine, NADPH and NADH. Allopurinol inhibited the hypoxanthine-supported anaerobic metabolism of 2,6-DNT by rat, but not human, liver cytosol. Dicumarol inhibited the NADPH-supported anaerobic metabolism of 2,6-DNT by human, but not rat, liver cytosol. These results indicate that xanthine oxidase contributes to the hypoxanthine-supported anaerobic metabolism of 2,6-DNT by human liver cytosol. PMID- 1413879 TI - A new carbamazepine metabolite in uraemic filtrate. AB - 1. After administration of carbamazepine (Tegretal) to an epileptic patient suffering also from uraemia, a previously unknown metabolite was detected in the haemofiltrate. It was identified as the 10,11-dihydro-10-hydroxy-carbamazepine-O beta-glucuronide. 2. Its identification was accomplished mainly by electron impact (EI), liquid secondary ion (LSI) mass spectrometry and n.m.r. spectroscopy. PMID- 1413880 TI - Lacidipine metabolism in rat and dog: identification and synthesis of main metabolites. AB - 1. The main metabolites of lacidipine were isolated from bile and plasma of rats and dogs following an oral dose of the 14C-labelled drug (10 mg/kg for rats: 2 and 1 mg/kg for dogs). They were identified by comparison of chromatographic and spectral data with authentic reference compounds synthesized ad hoc. 2. Five metabolites (I-V) were isolated and identified in dog bile by gradient h.p.l.c. with u.v. detection and h.p.l.c.-thermospray mass spectrometry. In all metabolites the heterocyclic ring has been oxidized to pyridine. Further biotransformation reactions involved hydroxylation of the methyl substituents and hydrolysis of the ethyl and t-butyl ester groups to produce carboxylic acids and a lactone. Some of these metabolites also occurred as glucuronide conjugates. 3. A metabolite retaining the intact dihydropyridine ring, the des-ethyl analogue of lacidipine (VI), was isolated from rat plasma where it accounted for 60% of the total circulating radioactivity up to 24 h after administration. To characterize this metabolite, h.p.l.c. with photodiode array u.v. detection also was employed. This compound was detected in dog plasma, but there was no evidence of its presence in dog bile samples. 4. Profiles of circulating metabolites were qualitatively similar in rats and dogs. Identified metabolites accounted for the large majority of total radioactivity in all the analysed samples. PMID- 1413881 TI - Thioethers as urinary metabolites of thiophene and monobromothiophenes. AB - 1. Thiophene and its two monobromo derivatives were administered to rats and the amounts of thioether excreted in urine were measured by an assay based on Ellman's reagent. This assay, which involves extraction and hydrolysis, was validated by determining extraction and hydrolysis efficiencies for several authentic thioethers including N-acetyl-S-(2-thienyl)-L-cysteine, a previously reported metabolite of thiophene and 2-bromothiophene. 2. The thioethers present in urine of animals dosed with thiophenes have been examined chromatographically. Contrary to previous reports, the present work indicates that S-substituted, N acetyl-L-cysteines (mercapturic acids) are not important thioether metabolites of thiophene in rats, and the small quantity of such compounds formed does not include either of the two simple S-thienyl derivatives. 3. The two monobromo thiophenes form higher proportions of thioethers than does thiophene, and one of these thioethers, arising from 3-bromothiophene, was identified, chromatographically, as N-acetyl-S-(3-thienyl)-L-cysteine. PMID- 1413882 TI - Lactose conjugation of sulphonamide drugs in the lactating dairy cow. AB - 1. 14C-Sulphamethazine (4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzene-[U-14C] sulphonamide; 220 mg/kg of body weight) was given orally or i.v. to lactating dairy cows. Milk collected from 0-48 h after dosing accounted for 2.0% (oral dose) and 1.1% (i.v. dose) of the total 14C-activity administered. 2. Sulphamethazine accounted for 70-79% (oral dose) and 54-75% (i.v. dose) of the total 14C in milk samples collected from 0-48 h after dosing. N4 acetylsulphamethazine accounted for 1-2% (oral dose) and 1-4% (i.v. dose) of the 14C in milk. 3. The major 14C-labelled metabolite in the milk was isolated and identified as the N4-lactose conjugate of sulphamethazine, a unique type of metabolite not previously reported. This metabolite accounted for 10-14% (oral dose) and 9-20% (i.v. dose) of the 14C-activity in the milk collected from 0-48 h after dosing with 14C-sulphamethazine. 4. N4-lactose conjugates of sulphapyridine, sulphamerazine, sulphathiazole, sulphadimethoxine and sulphaquinoxaline were present in the milk from cows orally dosed with these five sulphonamide drugs. PMID- 1413883 TI - Sex difference in the excretion of zenarestat in mice, rats, dogs and humans. AB - 1. Mice show a sex difference in the excretion of zenarestat similar to that seen in rats, but dogs and humans show no significant sex difference. 2. Female rats and mice, and both sexes of dogs and humans, appear to possess an active secretory mechanism in the renal excretion of zenarestat, which is lacking or relatively inactive in male rats and mice. PMID- 1413884 TI - The metabolism of benzo(a)pyrene by English sole (Parophrys vetulus): comparison between isolated hepatocytes in vitro and liver in vivo. AB - 1. Metabolites and DNA adducts of 3H-benzo(a)pyrene (BaP) formed by isolated hepatocytes from English sole (Parophrys vetulus) in vitro were compared to those in bile and liver of sole exposed i.m. to 3H-BaP. 2. English sole liver was perfused with a collagenase solution and hepatocytes were isolated with greater than 95% viability. Determination of kinetic parameters for metabolism of 3H-BaP showed a Km of 29 +/- 10 microM and an apparent Vmax of 1300 pmol BaP metabolized/10(6) cells per h. 3. Analysis of medium from hepatocyte cultures and bile by ion-pair h.p.l.c. showed significant amounts of radioactivity in regions where glucuronide and glutathione conjugates of BaP metabolites elute. No sulphate conjugates of BaP metabolites were detected. The major unconjugated metabolite formed by hepatocytes was the BaP-9,10-dihydrodiol. 4. Hydrolysis of glucuronide conjugates by beta-glucuronidase and reversed-phase h.p.l.c. analysis of chloroform-soluble metabolites showed the presence of BaP-7,8-dihydrodiol, 1 hydroxyBaP and 3-hydroxyBaP. The identities of these metabolites were confirmed by comparing their fluorescence spectra with those of standard BaP metabolites. 5. Analysis by 32P-postlabelling of the BaP-DNA adducts formed in isolated hepatocytes and liver revealed that major adducts detected are derived from the anti-7,8-dihydrodiol-9,10-epoxideBaP (anti-BaPDE) and syn-BaPDE. 6. Results show that the types of conjugated metabolites and BaP-DNA adducts formed in primary hepatocyte culture were similar to those in bile and liver of English sole exposed to BaP. Thus, isolated hepatocytes from English sole afford a reliable alternative to live fish for studies of the mechanisms of hepatic xenobiotic metabolism and DNA adduct formation in a species shown to be susceptible to induction of hepatocarcinogenesis by PAHs. PMID- 1413885 TI - The metabolism of 14C-tazadolene succinate in the dog. AB - 1. Beagle dogs dosed orally with 14C-tazadolene succinate excreted much of the dose in the urine (mean 63.1% in 5 days with most excreted in the first 24 h). A lesser proportion of the dose was excreted in the faeces (mean 20.7%) and again most of this was voided in the first 24 h. 2. Four metabolites were identified and quantified in the urine, namely 3-hydroxy-(M1), 4-hydroxy- (M2a), and 3 methoxy-4-hydroxy-tazadolene (M2b) and N-[2-(phenylmethylene)cyclohexyl]-beta alanine (M3). 3. In the 24 h urine, M2a and b glucuronides accounted for 17.7% dose, unconjugated M2a and b for 11.3%, and M3 for 18.3%. Insufficient M1 was present to be quantified. The same metabolites were seen in the 24 h faeces, but at lower concn. Thus M2a and b glucuronides, M2a and b, and M3 were 3.2%, 4.9% and 3.5% dose respectively. 4. All three phenols were present in plasma as their glucuronides as well as the beta-alanine derivative. They all had the same tmax of 2 h and t1/2 lambda 1 of the order of 1 h. PMID- 1413886 TI - The metabolism of cypermethrin in man: differences in urinary metabolite profiles following oral and dermal administration. AB - 1. The pyrethroid insecticide cypermethrin was administered orally to six male volunteers as a single dose of 3.3 mg (cis: trans 1:1) and dermally to six volunteers at a dose of 31 mg/800 cm2 (cis:trans 56:44) as a soya oil-based formulation. Urine samples were collected for up to 5 days and analysed for the metabolites cis and trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (DCVA), 3-phenoxybenzoic acid (3PBA) and 3-(4'-hydroxyphenoxy) benzoic acid (4OH3PBA) following an acid hydrolysis procedure. 2. Following oral dosing approx. equal amounts of (cis+trans DCVA) and (3PBA+4OH3PBA) were excreted with peak excretion rates occurring between 8 and 24 h after dosing. The ratio of trans:cis DCVA was on average 2:1. Based on DCVA measurements the amount of cypermethrin absorbed was estimated to be between 27% and 57% (mean 36%) of the administered dose. 3. Peak urinary excretion rates of metabolites occurred between 12 and 36 h after dermal dosing. The amount of metabolites derived from the phenoxybenzyl moiety (3PBA+4OH3PBA) was on average 4 times greater than the amount of (cis+trans DCVA) recovered in urine. The ratio of trans:cis DCVA was, on average 1:1.2. Based on the recovery of the phenoxybenzyl metabolites it is estimated that 0.85-1.8% (mean 1.2%) of the administered cypermethrin was absorbed. 4. These studies demonstrate marked differences in the urinary metabolite profile by the two routes, and provide an improved basis for determining the extent and main route of absorption of cypermethrin under occupational exposure conditions. PMID- 1413887 TI - A potentially new metabolic pathway: ethyl esterification of acitretin. AB - 1. The acidic retinoid, acitretin, was esterified to etretinate (ethyl ester) by rat and human liver 12,000 g supernatant. The amount of etretinate formed was increased by adding ethanol to the rat preparation. 2. This esterification almost certainly involves enzymic catalysis, and the amounts of etretinate formed were increased by the use of fresh rat liver. 3. Co-administration of acitretin and ethanol to rats resulted in a maximum plasma concentration of etretinate at approximately 1 h after dosing. Secondary maxima were induced by administering ethanol alone at 5 and 8 h after dosing with acitretin. 4. Comparison of acitretin and etretinate concentrations in rat portal and jugular vein plasma after ethanol administration indicated that the ester was formed mainly systematically, rather than during absorption. 5. The results of our study in the rat could indicate that the presence of etretinate in plasma of some patients being treated with acitretin may result from the intake of alcohol. PMID- 1413888 TI - Morphogenic development of the pancreas in the staged human embryo. AB - The Carnegie stage is widely applied in the field of human embryology, and it is more logical to analyze the embryos by this stage than CR length or menstrual age. In this study, the early development of the pancreas is studied by tissue observation and reconstruction using serial sections of 33 human embryo ranging from Carnegie stages 11 to 23. The dorsal pancreas develops from the dorsal wall of the duodenum in stage 12, and the ventral pancreas from the proximal part of the cystic primordium in stage 13 or 14 as a single epithelial thickening, but in one case, as a bilateral thickening which contains some isolated spaces. The rotation of the ventral pancreas starts in stage 15, and completes in stage 17. Surrounding connective tissue differentiates in stage 18. PMID- 1413889 TI - Effect of peripheral nerve stimulation on the dorsal horn cell activity in cats with cutaneous inflammation. AB - There are some reports showing that an experience of long-enduring pain causes a change in the pain transmission system, suggesting a plastic nature of the nociceptive system. However, most of the studies concerning the analgesic effect of peripheral nerve stimulation dealt with normal animal or human subjects. So, the present study was undertaken to investigate the effect of peripheral nerve stimulation on the dorsal horn cell activity using a tonic pain model, which was made by producing a cutaneous inflammation. The main results are summarized as follows. 1) The evoked activity by electrical or natural stimulation as well as spontaneous activity was enhanced, and the receptive field size was also expanded by the inflammation. 2) Peripheral nerve conditioning stimulation reduced the C response of the dorsal horn cell in the normal and inflamed group, and the degree of inhibition between the two groups showed no significant difference. 3) Inhibition of the C-response of the dorsal horn cells by peripheral conditioning stimulation was completely reversed by naloxone in the inflamed group whereas there was a partial block in the normal group. PMID- 1413890 TI - Network analysis of Korean health insurance policy-making process. AB - This study examines how the decision-making process evolved in Korea during the initial phases of introduction and implementation of National Health Insurance. This study analyses the official documents and interviews views made with government officials and related personnel. We used the method of network analysis and multidimensional scaling in order to demonstrate how the major participants in the decision-making process developed and changed under the contemporary political situations. In the pre-implementation stage around 1976, major concerns were concentrated around the issues of financial support for social insurance, the fee schedule and who ought to be covered first. The total number of participants of the health or health-related organization was 61, which included the President, the Minister of Health and Social Affairs, representatives of special interest groups, etc. In the actual implementation period of 1982, different issues were brought up by the major participants. The number of participants in this period declined to 44 with the deletion of 19 and with the addition of two newly formed health insurance organizations. By 1988, as the implementation reached its final decision period, disagreements were centered on progressive premium rating and the administration of National Health Insurance. The number of participants increased to 60 after the addition of 16 participants. The analysis of this paper may provide some insight for other countries which wish to establish National Health Insurance; as reference to the policy-making process, it may provide some suggestions for when to initiate and how to formulate National Health Insurance policies. PMID- 1413891 TI - Should all the N3 lymph nodes group metastasis be regarded as distant metastasis (M1) in curatively resected gastric cancer? AB - Recently, metastasis to N3 lymph nodes group was regarded as distant metastasis by the new TNM staging system due to poor overall survival. However, the 5-year overall survival rate of patients with metastasis to N3 groups was 34.5% after curative surgery. Moreover, in patients with metastasis to lymph node subgroups of #12, #13, #14, the overall 5-year survival rate increased upto 47.2% after curative resection and adjuvant chemotherapy. This was similar to that of the patients with metastasis to N1 and N2 lymph nodes groups. But in these highly tumor burden states, no survival benefit was found with the addition of immunotherapy to chemotherapy as we achieved in stage II and III. Therefore, we suggest that, at least, metastasis to #12, #13, #14 lymph nodes subgroups should not be categorized as a distant metastasis. And in these situations, active curative radical surgery with extended lymphadenectomy and adjuvant chemotherapy are recommended. PMID- 1413892 TI - Blood gas and electrolyte changes after tourniquet application in total knee replacement surgery. AB - The tourniquet is widely used in upper and lower extremity surgery in orthopedic practice. However, safe working guidelines for the application of the tourniquet are not clearly defined. The use of a tourniquet is an important step in performing total knee arthroplasty, and it seems plausible that mechanical damage is directly related to the height and the duration of the pressure of the tourniquet applied. Even the tourniquet pressure which is widely accepted in clinical practice, if it is applied for several hours, would permanently damage not only tissues directly under the tourniquet but also the muscles and the nerves distal to the tourniquet. The resultant ischemia to limb produces local changes including hypoxemia, acidosis and hyperkalemia. Relatively little is known about the systemic effects of tourniquet release when the patient is undergoing total knee replacement surgery under a general anesthesia. Therefore, we studied the systemic effects. The results were as follows: 1) Approximately five minutes after the tourniquet was released there was a statistically significant increase in mean heart rate.: 2) Serum potassium levels tended to increase significantly until five minutes while the serum sodium level rose significantly only one minute, and the lactate level rose significantly for only two minutes after tourniquet released; 3) PaCO2 increased for five minutes after tourniquet release and remained elevated for 30 minutes; 4) PaO2 did not change significantly two minutes after tourniquet release; 5) The mean pH dropped to 7.34 and remained low for over five minutes. PMID- 1413893 TI - Luminal development of the eustachian tube and middle ear: murine model. AB - The purpose of this study was to describe the luminal development of the murine eustachian tube and middle ear. Thirty specimens, aging from gestational day 11 to postnatal day 21, were investigated through the light microscopic observations. The present study also used digitizer, computer, and serially sectioned temporal bone specimens for three-dimensional reconstruction to measure the volume of the eustachian tube and middle ear cavity at different gestational and postnatal ages. The first pharyngeal pouch elongated during gestational day 12 to form the tubotympanic recess. Between gestational day 13 and 14 this tubotympanic recess extended to the middle ear area. A rapid increment in the volume of the tubotympanic recess was noted between gestational day 15 and 16. At this age, a definite division of the tubotympanic recess into the eustachian tube and middle ear cavity was observed. During the postnatal period, the maximum change of the middle ear volume was noted on postnatal day 11 when the mesenchymal tissue in the middle ear cavity disappeared completely. PMID- 1413894 TI - Impact of clinical history on film interpretation. AB - We performed a study to determine whether clinical history gives a positive or negative influence on X-ray film interpretation. One hundred and nine patient's radiograms, consisting of 55 normal and 54 abnormal cases (136 abnormalities), were interpreted twice by three pairs of residents in radiology and a pair of qualified radiologists, without clinical history first and with clinical history next. The interpreters recorded diagnosis and confidence level of normal or abnormal findings on a six-point scale. Analysis of receiver operating characteristic (ROC) curves showed that knowledge of clinical history improved diagnostic accuracy. Residents, especially beginners, should be advised to obtain clinical history whenever they read radiograms. PMID- 1413895 TI - Surgical intervention in patients with aplastic anemia. AB - Eighteen surgical procedures have been performed on 14 cases of aplastic anemia (AA). Of the 10 major surgical procedures, 7 were emergency and 3 elective. The median duration from the diagnosis of AA to major surgery was 0.5 months (3 days 47.3 months), and the median survival after surgery was 12.3 months (4 days-38 months). The hematological status of AA at the time of major surgery were 3 in partial response (PR), 2 with no response (NR) and 5 at diagnosis, respectively; and those after major surgery were 2 with complete response (CR), 2 in PR, 1 with minimal response, and 2 in NR. Three postoperative complications were sepsis, pneumonia and atelectasis encountered in 2 cases. A total of 3 deaths were caused by infection and cancers. Considering the fact that surgery may not only control complications, but offer the opportunity to give effective therapy for AA and therefore improves chances for survival, it is strongly suggested that active surgical intervention should be performed if the patient's status is not terminal. PMID- 1413896 TI - Serum interleukin-6 in Kawasaki disease. AB - Kawasaki disease (KD) is an acute febrile illness of infancy and early childhood. In spite of extensive studies, the cause of KD is not known. Interleukin 6 (IL-6) has manyfold biological functions involved in the immune or inflammatory responses of the host to various stimuli. Here the author investigated whether IL 6 might be responsible for manifestations of KD, such as immunoglobulin hypersecretion, lymphocyte activation and systemic vasculitis. Serum IL-6 levels in KD were determined by ELISA. Usually sera from healthy children contained only negligible levels of IL-6. Serum IL-6 was markedly elevated in all patients with acute KD, which gradually decreased during the course of the disease. Serum IL-6 correlated with serum concentration of C-reactive protein and with serum soluble interleukin-2 receptor level, but did not show any correlation with peak platelet count during subacute phase of the disease. Increased serum IL-6 level did not show any relation to development of coronary aneurysms and dilatation. Further studies will be needed to examine the source and the pathogenetic roles of increased serum IL-6 in KD. PMID- 1413897 TI - Gastric varices: diagnosis with duplex Doppler ultrasonography--a case report. AB - The diagnosis of gastric varices may be difficult due to their anatomic location and morphology. In this abstract we describe a case of gastric varices, of which a duplex Doppler sonography was useful in the diagnosis, that was initially suggested as submucosal tumor of the stomach by barium studies and endoscopy. PMID- 1413898 TI - Congenital self-healing reticulohistiocytosis--report of a case of the solitary type and review of the literature. AB - A 2-month-old female infant presented with a single hemorrhagic crusted papule on the chin present since birth. No visceral involvement could be demonstrated. The lesion involuted spontaneously with scarring in 3 months. Mononuclear cells in the cutaneous infiltrate were Langerhans cells with typical Birbeck granules which positively stained with S-100 protein. This case is the solitary type of congenital self-healing reticulohistiocytosis. PMID- 1413899 TI - Radiotherapeutic management in carcinoma of the uterine cervix: GOG experience. PMID- 1413900 TI - [Stage classification of non-Hodgkin's lymphoma]. PMID- 1413901 TI - [New aspects in the prevention and therapy of cytostatic drug-induced nausea and vomiting]. PMID- 1413902 TI - [Clinical aspects, diagnosis and therapy of echinococcosis in the human]. PMID- 1413903 TI - [Risks and prevention in orthotopic liver transplantation and persistent infection with hepatitis type B and type delta viruses]. PMID- 1413904 TI - [Detection of Helicobacter pylori infections by antibody determination]. PMID- 1413905 TI - [Sexual and contraceptive behavior of adolescents]. PMID- 1413906 TI - [Medical care in Saxony between 1927 and 1924]. PMID- 1413907 TI - [Obesity--pacemaker of the metabolic syndrome]. PMID- 1413908 TI - [Disorders of lipid metabolism within the scope of the metabolic syndrome]. PMID- 1413910 TI - [The lactulose challenge. Part 2. Importance of regulation of enteric bile acid circulation by lowering pH value for lithogenesis]. PMID- 1413909 TI - [The lactulose challenge. Part 1. On the cholesterol lowering effect of lactulose]. PMID- 1413911 TI - [Hyperuricemia and gout]. PMID- 1413912 TI - [The metabolic syndrome--conclusions for general practice]. PMID- 1413913 TI - [Surgery of intestinal arteries. Part 2: The chronic intestinal ischemia syndrome]. PMID- 1413914 TI - [Determination of patients' blood glucose in ambulatory practice]. PMID- 1413915 TI - [The incidence of abnormalities after flu epidemics]. PMID- 1413916 TI - [Adolescents and computers: attitude, personality and motive for interaction]. AB - This empirical study was undertaken to clarify controversial points emanating from previous theoretical and empirical papers dealing with apparently negative consequences on the personality development of young people who have at least a causal working-acquaintance with computers. We tested 174 persons of both sexes (age: 14-18 years) with a "Computer-Attitude-Questionnaire" and the "Mehrdimensionaler Personlichkeitstest fur Jugendliche" (Schmidt, 1981; "Multidimensional-Personality-Test"). A subgroup of 63 persons who have access to and do avail themselves of computers on a regular basis (as leisure-time activity) also answered the "Computer-Motive-Questionnaire". Statistical analyses revealed that the personality test-values of young people with a positive attitude toward computers range within the test-norm. The data for these people describe them as stress resistant, emotionally stable, well-balanced, sociable, achievement-oriented, and less aggressive. PMID- 1413917 TI - [Processing steps in perception of speech sounds]. AB - The aim of this study is to investigate whether speech sounds--as is stated by the widely accepted theory of categorical perception of speech--can be perceived only as instances of phonetic categories, or whether physical differences between speech sounds lead to perceptual differences regardless of their phonetic categorization. Subjects listened to pairs of synthetically generated speech sounds that correspond to realizations of the syllables "ba" and "pa" in natural German, and they were instructed to decide as fast as possible whether they perceived them as belonging to the same or to different phonetic categories. For 'same'-responses reaction times become longer when the physical distance between the speech sounds is increased; for 'different'-responses reaction times become shorter with growing physical distance between the stimuli. The results show that subjects can judge speech sounds on the basis of perceptual continua, which is inconsistent with the theory of categorical perception. A mathematical model is presented that attempts to explain the results by postulating two interacting stages of processing, a psychoacoustical and a phonetic one. The model is not entirely confirmed by the data, but it seems to deserve further consideration. PMID- 1413918 TI - [Biofeedback of slow brain potentials]. AB - Slow cortical potentials constitute neurophysiological indicators of cortical excitability. Behaviorally they correlate with attention and motor preparation. A system for biofeedback and self-regulation of slow cortical potentials (SCP) has been developed. The portable system allows on-line visual feedback of filtered and corrected slow brain potentials in a predetermined sequence of trials. Three different algorithms for transforming the original SCP-signal into a feedback signal have been developed and were compared in a controlled outcome study. With the optimal feedback method subjects were able to produce cortical positivity and negativity on command after three sessions. Increases and decreases of negativity of up to 20 microV were also achieved. Therefore a simple and portable PC-based device for the clinical application of SCP-biofeedback is now available. PMID- 1413919 TI - [Characteristics of changes of personal odor after experimental bone marrow transplantation]. AB - In an operant conditioning paradigm 4 Balb/c inbred strain mice were conditioned to discriminate between urine samples of two other inbred strains. The purpose was to examine whether or not the known stimulus configuration during training had any effect upon the rate of recognition of other stimuli. On the basis of this procedure, we subsequently investigated the extent to which an allogeneic bone marrow transplantation interferes with the olfactory identity of an individual. For the transplants a strain was inbred which had no contact to the animals tested, a procedure used for the first time here. Furthermore, also for the first time, it was possible to demonstrate in a direct comparison, the role played by donor versus recipient characteristics on the olfactory composition of the recipients odor. PMID- 1413920 TI - [Psychological variables and success of interpersonal coordination of motor performance tasks]. AB - This paper examines which dispositional, cognitive and motivational variables will contribute to improved multi-person motor coordination. The study conceptually refers to a control-theoretical approach of continuous motor behavior. According to this approach interpersonal behavior should be determined by similar regulative processes as is individual behavior. Results of a laboratory study with 18 three-person groups support assumptions of this approach. Substantial effects on group performance are found for dispositional and motivational variables. Theoretical implications of the results obtained are discussed. Conclusions for applied issues are derived. PMID- 1413921 TI - [The effect of "stress hormones" on emotional sensitivity]. AB - Stress is associated with an increased secretion of hormones from the hypothalamus-pituitary-adrenal-axis (HPA-axis). Once released into the blood stream they induce a number of adaptive changes that may also have pertinence to brain functions, resulting, for example in alterations of mood. To provide evidence for a mediation of mood changes by stress related hormone secretion, the influences of a short-term administration of hormones of the HPA-axis on mood and activation were assessed in a total of 182 healthy men (aged between 18 and 34 years in 7 experiments). Effects of intravenously administered hormones on self perceived mood and activation were assessed by a standardized adjective checklist (Eigenschaftsworterliste) in placebo-controlled, double-blind experiments during rest. Results indicated no effects following corticotropin releasing-hormone or cholecystokinin, but specific effects resulted after vasopressin, oxytocin, ACTH related hormones, and cortisol. Vasopressin and oxytocin increased activation and attenuated arousal and anger, ACTH-related hormones increased sensitivity and diminished extraversion, while cortisol increased activation and concentration. It is concluded that hormones of the HPA-axis specifically affect mood and activation. The pattern of hormonal changes in mood may have adaptive functions by preparing for behavioral and cognitive coping with stress. PMID- 1413922 TI - [Changes in spontaneous slow potentials and visually (flash) evoked potentials in response to stimuli with no performance implication]. AB - The influence of spontaneous slow potential shifts (SPSs) on visual (flash )evoked potentials (VEPs) was studied. Eighteen subjects received 100 flashes. The sequence of interstimulus-intervals (ISIs) was pseudo-randomized. ISI durations were 3, 5, 7, 9 or 11 seconds. EEG was recorded from Fz, Cz, Pz and Oz with linked-mastoids as reference. EEG was EOG-corrected and VEPs were calculated for preceding positive SPSs. Averaging was done for local SPSs; VEP pairings as well as VEPs were calculated over occipital SPS-polarities. Results showed an influence of SPSs on VEP-amplitudes. Differences in amplitudes were interpreted with the 'activation-correction'-hypothesis and with the 'ceiling'-hypothesis. Negative SPSs were followed by smaller negative peaks, and positive SPSs were followed by smaller positive peak-amplitudes. Differences in latencies of N145 P300 peak-to-peak amplitudes after SPSs of different polarity were explained with the threshold-regulation hypothesis. Spectral-analysis were done for SPS-data. There were only poor effects, showing increased parietal alpha 2-power after negative SPSs. PMID- 1413923 TI - [Modification of autoregulation of intrinsic physical processes in field dependent subjects: a study of performance in heart rate biofeedback]. AB - Witkin, the founder of the concept of "field dependence", assumed that there is a relationship between field dependence and body perception. However, this hypothesis was never investigated experimentally in a well-controlled study. Twenty healthy subjects learned to increase and decrease their heart rate dependent upon two discriminative stimuli. In order to increase and decrease their heart rate they received exteroceptive feedback (movements of a rocket-ship on a video screen). Each trial lasted 6 s. The distance of the rocket-ship from a certain point indicated the amount of the achieved increase or decrease. Field dependent subjects scoring higher in field dependency as measured by the Embedded Figures Test were poorer at heart rate control on feedback and transfer trials (test trials with feedback removed) than were subjects scoring low in field dependency. This result may be of therapeutic interest in the application of behavioral medicine to psychosomatic and psychiatric disorders. PMID- 1413924 TI - [Unconscious induction of emotions and unintended change in behavior]. AB - The problem of most mood induction procedures in psychological laboratories is located in their demand characteristics. The subjects either have to help change their mood actively, or are at best only passively aware of the induction process. To overcome the necessity of consciousness of the mood induction procedure we developed a technique based on the involuntary tendency to imitate the expression of perceived faces ("emotional infection"). Three different mood induction conditions--operationalized by means of happy, neutral, or sad pairs of faces, which had to be compared in spite of their age--were imbedded in an experiment disguised as, research in perception'. The results show mood influences only in the behavioral measures: Happy induced subjects wrote significantly faster than neutral and sad ones. In contrast, the self description data--measured via mood adjectives--showed no typical changes due to the induction condition. The subjects seemed to be unaware of the cause and the effect of their changed mood. PMID- 1413925 TI - [Endoscopic sclerosing of esophageal varices--technique, possibilities and limits of the method]. AB - The paper intends to give a survey of the significance of endoscopic sclerotherapy in gastro-esophageal varices. The control of an acute bleeding can be achieved in a high percentage (70-95%). However, the hospital mortality has persisted in 30% depending on early rebleeding episodes and alterations in hepatic function. Controlled trials have confirmed a lowering of rebleeding risk as well as an improved survival by repeated sclerotherapy. The effectiveness of prophylactic sclerosing before the first bleeding is uncertain because of contrary results published. A prophylactic application seems to be favourable in patients at high risk of bleeding only. PMID- 1413926 TI - [Incidence of local complications after heart catheter studies and their imaging with intravenous digital subtraction angiography: a retro- and prospective study]. AB - Frequency of local complications following punction of the femoral artery aimed to cardiac catheterisation has been checked with 1051 patients retrospectively as well as 300 patients prospectively. Intravenous DSA was carried out when symptoms like stenotic murmurs, pulsations, hematoma, swelling or resistance within the concerned inguinal region appeared with suspicion diagnose of pseudoaneurysm, arteriovenous fistula or any other complications of vessels. The retrospective study reviewed a rate of complications of 1.62% and the prospective study a rate of 2.7%. The study reviewed that by using of DSA-checkings during a time period of 4 up to 10 month later no rest aneurysm or AV-fistula could be proved. That means a spontaneous thrombose took place with patients without operation indication. Significant connections were found between clinical pathological findings next to the position of punction and the occurrence of local complications. The single symptoms like stenotic murmurs or large hematoma are statistically proved indications to a complication of vessel. There is no connection between findings like pseudoaneurysm or AV-fistula and small hematomas next to the punction position. The intravenous DSA has been proved as easy and proof method with a small quantity of complications for the inclusion and differentiation of local complications following punction of the artery femoral. PMID- 1413927 TI - [Ventilation and hemodynamics as control parameters of spa treatment]. AB - Physical endurance training as practised at spas in the active treatment of hypertension will usually result in an increase in oxygen supply reserves and will also improve haemodynamics, so that it could help in objectively identifying the success of cardiovascular treatment. For this reason we conducted a bicycle ergometer load test in recumbent position in a group of 23 male hypertensives in stages I and II (age between 25 and 58 years) before and after a treatment course at a spa of 4 to 5 weeks' duration. The measurement parameters were ECG, blood pressure, cardiac output and the ventilatory parameters tidal volume, oxygen uptake, respiratory equivalent and respiratory quotient. Significant blood pressure reductions were seen if the load did not exceed 75 watts. The treatment course had a definite influence on cardiac output at rest and under stress. The treatment course achieves reduction and largely also normalisation of the tidal volume which is otherwise higher than in healthy persons. No influence is exercised on the respiratory equivalent. Reduction of the tidal volume and of the oxygen uptake, as well as reduction of the respiratory quotient after the treatment course can be interpreted as an improvement in the economy of the cardiovascular system. The ventilatory parameters are only conditionally suitable for arriving at an objective assessment of the curative effect of the treatment course. PMID- 1413928 TI - [Population screening on a population level in Leipzig within the scope of the Bavarian cholesterol project]. AB - Cholesterol determinations of 15.391 inhabitants of Leipzig were carried out in November 1990 within the Bavarian Cholesterol-Screening-Project. The aim of this screening on population basis was to identify individuals with elevated blood cholesterol levels as one of the risk factors of atherosclerosis. Capillary blood cholesterol was measured by means of the Reflotron dry-chemistry system (Boehringer, Mannheim). 27% of the inhabitants of Leipzig show cholesterol levels lower than 5.2 mmol/l as recommended by the European Society of Atherosclerosis Research. Furthermore the characteristic age dependence is seen. In comparison with the town Nurnberg lower mean cholesterol values were found in Leipzig. PMID- 1413930 TI - [Developmental trends in the malpractice process. II: Legal process and legal malpractice]. PMID- 1413929 TI - [Selection modalities in the history of the medical faculty of the Halle University. II. The 19th century]. AB - Up to the 19th century a university chair was offered to a physician, surgeon or researcher at the Department of Medicine of the University of Halle mainly by means of a decree issued by the Government or state. The statutes of the Departments of Medicine of different universities were revised and updated in the 19th century, providing for a little more leeway in respect of such calls to a university, giving the universities a right to suggest to the relevant ministers as to who, in their opinion, should receive a call to the chair of professor or assistant professor. Examples taken from the history of the university of Halle, however, show that this freedom of action was rather limited and that royal or government decrees had to be carried out even if they contradicted the conceded right to nomination. PMID- 1413931 TI - [Physician's rights--what are they?]. PMID- 1413932 TI - Long-term results of treatment of malignant non-Hodgkin's lymphoma of the stomach. AB - Our experience with 66 endoscopic-bioptic diagnosed malignant non-Hodgkin's lymphomas (NHL) showed that in most of them (57 of 66 patients) a tumor stage IE or IIE was present. All 57 primary gastric lymphomas were B-cell-lymphomas arising from the mucosa-associated lymphoid tissue (MALT). After curative primary gastric resection in stage IE and IIE the 5-year survival rate was 81%, and the 5 years lymphoma-related survival rate was 88%. These results are superior to those reported in the literature. The following two points are probably of importance for improving the prognosis: early diagnosis made possible by better knowledge of the infiltrative-flat type of tumor growth (38 out of 57 patients, including 23 cases in which infiltration was limited to mucosa and submucosa = "early lymphoma"), and extensive preoperative staging. The infiltrative-flat type, which is difficult to diagnose endoscopically, usually shows low-grade malignancy on histology (76%; in early lymphoma 83%) and has an excellent prognosis when submitted to surgery. In our experience the question as to whether additional treatment by chemotherapy and/or radiotherapy improves the prognosis of NHL of the stomach remains unanswered and further studies are needed. PMID- 1413933 TI - [The time requirement for endoscopic diagnosis and therapy: results of a multicenter study]. AB - For evaluation of the time requirements for endoscopic diagnostic and therapeutic procedures data of 13,321 patients gathered from 155 endoscopic units were collected. Time requirements were calculated for preparation of the procedure, examination and after-care of patients and instruments. The data indicate, that time requirement is significantly influenced by the special procedure. Therefore, calculation of the time requirement of an individual unit needs exact consideration of the frequency of different procedures. Only cleaning of instruments by washing machines could be shown to reduce time requirement. Education of endoscopists was demonstrated to be time intensive. Age (exemption children) sex of patients and video-endoscopy did not effect duration of procedures. PMID- 1413934 TI - [Gallbladder motility in diabetic patients with and without cardiovascular neuropathy]. AB - In 50 diabetic patients without gallstones, including 26 patients with cardiovascular autonomic dysfunction, and 60 normal volunteers the fasting volume and volume reduction of the gallbladder after a liquid fatty meal were determined ultrasonically in intervals of ten minutes up to one hour. Simultaneously the gastric emptying of the liquid meal was followed by ultrasound imaging. Despite an association of other complications of diabetic disease (peripheral neuropathy, retinopathy) with autonomic cardiovascular dysfunction, an altered gallbladder resting volume or impaired fat-induced volume reduction was not evident in this group of patients when compared the diabetics without cardiovascular dysfunction or controls. The time to reach the minimal residual gallbladder volume was only tendentiously prolonged in diabetics with autonomic cardiovascular dysfunction. The residual volume of the stomach showed no significant difference between the three study groups using a liquid test meal. In conclusion neuropathic dysfunction of the gallbladder is unlikely to play a major pathogenetic role in the development of gallstones in diabetic patients. PMID- 1413935 TI - [Routine gastroscopy before laparoscopic cholecystectomy: evaluation of the technology in 376 patients]. AB - We performed endoscopy of the upper digestive tract in 376 patients before elective laparoscopic cholecystectomy. Abnormalities were found in 60 (15.9%); 14 patients had peptic ulcers, 15 gastric erosions, and 11 oesophagitis. Because of endoscopic findings 30 patients were treated medically and 2 by endoscopic polypectomy. Endoscopy lead us to cancel cholecystectomy in 4 patients; in 2 the complaints have persisted. Patients with abnormal endoscopic findings showed few significant differences in 40 variables (history and symptoms) compared with patients with normal findings. The incidence of ulcers, erosions or oesophagitis in patients over 72 years of age without loss of weight was 28.6%, compared with an overall incidence of 10.6%. Endoscopy confined to this group of patients, however, would have shown only 15% of all lesions. Consequently these predictors for endoscopic abnormalities had no practical benefit. Technology assessment according to the criteria of Fineberg et al. showed a health improvement for only 2 patients (0.5%). We conclude that routine endoscopy before laparoscopic cholecystectomy is not clinically useful in patients with symptomatic gallstone disease. This is exclusively related to patients with typical gallstone symptoms according to our definition. PMID- 1413936 TI - Sclerosing encapsulating peritonitis: differential diagnosis to peritoneal encapsulation and abdominal cocoon--a case report. AB - A 59 year old man presented with symptoms of partial bowel obstruction. Small bowel x-ray studies did not allow to identify the nature of the intestinal process in the upper ileum. At laparotomy small bowel encapsulation with a whitish membrane was encountered. Despite partial removal of this membrane small bowel obstruction persisted and two weeks postoperatively the patient died of peritonitis and cardiac insufficiency. Autopsy findings revealed massive fibrous adhesions in the abdomen with granulomatous inflammation. The presence of foreign body giant cells and bifringent crystals were characteristic for talcum powder. The latter suggested a causal role of an appendectomy 45 years earlier. The diagnosis of sclerosing encapsulating peritonitis as established in our patient needs to be separated from peritoneal encapsulation, a congenital malformation, and abdominal cocoon, which contains histological elements of inflammation. This case report should draw attention to these entities in the differential diagnosis and surgical management of small bowel obstruction. PMID- 1413937 TI - Splenic hematoma in acute pancreatitis. Role of coagulation disorders. AB - Splenic hematomas are infrequent complications of acute pancreatitis. In some cases, local factors that may play a role in the pathogenesis of the hematoma (thrombosis of the splenic artery or veins, intrasplenic pseudocysts, perisplenic adhesions, enzymatic digestion) are found. In the absence of local factors, the etiology of splenic hemorrhage remains unknown. We report two cases of splenic hematoma occurring during an acute necro-hemorrhagic pancreatitis associated with renal failure that required renal replacement therapy (hemodialysis and continuous arteriovenous hemodialysis). In both cases, more than half of splenic parenchyma was affected by multiple infarctions. No local factors responsible for the splenic abnormalities were detected in either case. Thrombosis of the splenic arterial microcirculation and a coagulation disorder consistent with disseminated intravascular coagulation was detected in one patient. In the second patient, coagulation disorders secondary to either liver disease, pancreatitis and its septic complications, or extracorporeal circuit heparinization for renal replacement therapy were present. Coagulation disorders should be considered whenever a splenic hematoma is found in a patient with acute pancreatitis. Disseminated intravascular coagulation may be the etiology of a splenic hematoma in acute pancreatitis. PMID- 1413938 TI - [Spontaneous bacterial peritonitis]. AB - Patients with liver cirrhosis and ascites suffer from spontaneous bacterial peritonitis (SBP) in up to 25%. The typical clinical signs are abdominal pain with tenderness and fever. 30% have no signs of peritonitis. Then clinical worsening, encephalopathy, rising serum creatinine levels, and therapy resistant ascites may be the only clinical features. SBP must be differentiated from bacterascites and culture negative neutrocytic ascites by the polymorphonuclear neutrophil (PMN) count in the ascites and the presence of positive culture results, which has prognostic implications. Gram negative rods from the colon play an important etiological role in SBP. Gastrointestinal bleeding, lack of serum complement, a low ascites protein and the extent of intrahepatic shunts predispose to SBP. Then, prophylaxis with the comparable drugs neomycin and norfloxacin is indicated. Coexisting encephalopathy has to be treated by the therefore effective neomycin. Otherwise, norfloxacin is the drug of choice because of better acceptance and lower costs. Chemical parameters of the ascites (pH value less than 7.4; LDH and lactate greater than serum levels; glucose less than 50 mg%) help to assess the severity of peritonitis. The course of ascitic PMN under therapy and the time of persisting positive cultures can discriminate SBP from secondary peritonitis. Antibiotics of choice are amoxicillin-clavulanic acid and cefotaxime. Short course therapy (5 days) is a effective as long course therapy (10 days). Today SBP is no more life-threatening because diagnosis, prophylaxis and therapy have improved. However, complication rate of patients with liver cirrhosis and ascites has not changed. PMID- 1413939 TI - [Formal decision aids in gastroenterology--results of a survey]. AB - Formal decision aids such as scores, decision-trees and expert systems, are recommended for supporting research and daily clinical work. In the field for gastroenterology it is unknown, to which degree these tools are accepted and applied in clinical routine. We therefore conducted a mail survey in order to find out whether clinical gastroenterologists know, use or want formal decision aids. To all clinical members of a german gastroenterological scientific society (Deutsche Gesellschaft fur Verdauungs- und Stoffwechselkrankheiten, n = 584) an information leaflet and a questionnaire was sent. The form contained questions about use, knowledge and requests with respect to decision-aids in gastroenterology and concerning the attitude to computerized decision-aids in general. 584 clinicians received the questionnaire, 215 sent it back for analysis (39%). Formal decision-aids were used by half of the survey participants (56%), mainly three scores (Child-Pugh, Best and other indices for inflammatory bowel disease, Ranson) and four classifications (TNM, Forrest, Savary-Miller, Paquet). Computer-based formal decision-aids (e.g. expert systems) were used by a minority. Clinicians, who applied formal decision-aids stated more frequently a request for further decision-aids (72%) than those who did not (46%). A considerable part of the survey participants believed that computerized decision aids will come into clinical routine (52%) and will improve education (37%) and clinical practice (35%). 88% were convinced, that decision-aids should be tested in controlled clinical trials before a clinical use can be recommended. There is a discrepancy between propagation of formal decision-aids and it's clinical use. Only a few scores and classifications are used in clinical routine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413940 TI - [Motilin and motilides--future perspectives for therapy of gastrointestinal motility disorders]. PMID- 1413941 TI - [What factors modify the condition of the newborn infant in emergency cesarean section?]. AB - Based on 207 emergency caesarean sections carries out in 66 maternity units in North Rhine Westphalia, the condition of the newborns (pH, UA and Apgar-index after 1 minute) was examined focusing the dependence of these variables from the time management (5 time factors were analysed). Rank-correlation coefficients according to SPEARMAN were calculated and a stepwise multiple regression analysis was performed. We found a significant (P less than 0.005) positive correlation on the one hand between the preparation time for the caesarean-section (time 1) and the actual pH (UA) and on the other hand between the total time (decision to perform a caesarean section up to the delivery of the baby (time 3)) and the actual pH, UA. No significant correlation was found between the time-factors and the Apgar-index (1 min). As the correlations are positive, this means that very low pH values are associated with short time intervals and high pH values with longer time intervals respectively. We concluded, that in case of an emergency caesarean section the urgency of the emergency itself controls and determines the time management. The spatial situation in each hospital which is reflected in the time factors 4 and 5 seems to be of less important for the overall result. PMID- 1413942 TI - [Diagnosis and therapy of hemodynamic disorders. A contribution to the management of pregnancies with threatened premature labor]. AB - 114 pregnant women (without multiple pregnancies) with premature labour were examined in a randomized prospective study. Pulsatility index (PI) in the uterine artery and fetal thoracic aorta was the parameter we used for the examination, the determination of which was done with doppler sonography at the time of hospital admission. Therapy with beta-sympathomimetics alone or additionally either Oxygen inhalation therapy or transcutaneous dorsal nerve stimulation were conducted and the pulsatility index was controlled at intervals of one and two weeks after initiation of the aforementioned therapy. The negative correlations which we determined between pulsatility index and prolongation of duration of pregnancy, gestational age at the time of delivery and birth weight were significant. This confirms the clinical importance of maternal perfusion already at the time of admission for the clinical end-results. Similarly significantly negative correlations between pulsatility index of uterine vessels, weight percentile of the corresponding newborns and antenatal CTG scores (Fischer) verify the close connections between the hemodynamic, nutritional and respiratory partial functions of the fetoplacento-maternal unit. The clinical results after normalization of an impaired perfusion were found to be improved significantly after a combined therapy with beta-sympathomimetics and transcutaneous dorsal nerve stimulation (TNS) as compared with beta-sympathomimetic therapy alone. These results justify the recommendation that doppler sonographic measurements of utero-placental perfusion can be used for the diagnostic and therapeutic concept in pregnancies with premature labour. PMID- 1413944 TI - [Unpreventable effects of neonatal intensive care on the later development of extremely small premature infants]. AB - This review of the literature presents the pooled data from several perinatal centers throughout the world published during the last three years. It regards the longterm prognosis of extremely low birthweight infants (less than 1000 g). Since the introduction of neonatal intensive care the mortality rate dropped from greater than 90% to less than 50%. On the other hand the morbidity rate improved only slowly. Recent reports from the Anglo-American literature show that among the survivors 13.7% are seriously and 25.1% mildly handicapped. 60-70% of the extremely low birthweight infants, despite of normal IQ's, are experiencing school problems. Most of them have cognitive, perceptual and motor deficits combined with behaviour problems ("the new morbidities"). The incidence of cerebral palsy remained unchanged (6-8%) over the last two decades. Until now, there is no significant effect of the surfactant therapy on the morbidity rate. The rate of serious longterm disability increases with decreasing birthweight. The results of the Anglo-American and German follow-up studies differ only slightly. PMID- 1413943 TI - [The effect of bovine surfactant in premature infants with respiratory distress syndrome. Results of an open, multicenter study]. AB - We investigated the effects of a bovine surfactant (SF-RI 1, Alveofact) in very low birth weight infants (VLBW, b.w. 500-1500 g) with established respiratory distress syndrome (RDS; definition: FiO2 greater than or equal to 0.6 or peak inspiratory pressure greater than 22-28 cm H2O). Fifty mg/kg b.w. bovine surfactant was administered intratracheally as a bolus, if the acute response was unsatisfactory (FiO2 greater than 0.5), further administrations of surfactant up to a maximum cumulative dose of 200 mg/kg b.w. were permitted. One hundred and sixty-four VLBW infants (gestational age 28.0 +/- 2 wks; b.w. 1054 +/- 251 g; mean +/- SD) with a mean FiO2 of 0.84 +/- 0.15 were enrolled in the study. Maximum improvement in oxygen requirements was observed 1/2 h post administration (FiO2 0.53 +/- 0.22); incidence of complications during the neonatal period: pulmonary interstitial emphysema 26%, pneumothorax 10%, patent ductus arteriosus 37%, intracranial hemorrhage 47%. The overall survival rate was 61%, survival rate without bronchopulmonary dysplasia (BPD) was 47%. A multiple regression analysis was performed in order to identity factors determining survival without BPD (p less than or equal to 0.05). We observed a positive correlation for gestational age and birth weight and a negative correlation for pretreatment oxygen requirements. For further optimizing surfactant-therapy in VLBW infants with RDS, studies are mandatory using intervention criteria at lower FiO2-values and higher initial doses of bovine surfactant. PMID- 1413945 TI - [Umbilical cord complications as a cause of intrauterine fetal death]. AB - In a group of 71 intrauterine fetal deaths in monozygotic pregnancies, umbilical cord complications were the cause of death in 11 cases (16%). These included 5 umbilical knots, 3 loops, and one case each of torsion with constriction, umbilical prolapse and velamentous insertion (with rupture of the umbilical vessels). The relative importance of these umbilical complications is pointed out and discussed in regard to clinical and pathological factors. PMID- 1413946 TI - [Effects of prostaglandin E1 analogs on the cervix--observations with vaginal sonography]. AB - In this study participated 17 patients, in whose pregnancies not viable malformations or intrauterine deaths were diagnosed. The termination of the pregnancies was done with PG-E-1 suppositories Gemeprost (Cergem) 1 mg. Collectively the patients received 3 Cergem suppositories applicated all 3 hours. Before beginning therapy and every 4-6 hours a vaginosonography was done. The cervical changes under the influence of Gemeprost were documented vaginosonographically. The measurements before Gemeprost treatment showed an average cervical length of 44.2 +/- 6.3 mm, a width of 29.5 +/- 1.7 mm and an internal os of 2.5 +/- 0.5 mm. The results of the second ultrasound showed a length of 30.6 +/- 4.1 mm, a width of 32.3 +/- 2.5 mm and an internal os of 7.0 +/- 3.0 mm. The last measurements (ca. 107 minutes before abortion) showed a remaining of cervical length of 15.2 +/- 4.5 mm, a width of 41.5 +/- 4.6 mm, an internal os of 19.2 +/- 4.1 mm and the amniotic membranes bulged into the cervical channel. PMID- 1413947 TI - [Cervix reconstruction after amniotic fluid puncture in amniotic sac prolapse in the second trimester]. AB - The possibility and the problems of an surgical technique because of cervical insufficiency in the 2. trimester with a hourglass amniotic prolapse is shown in three cases. A new concept including amniocentesis and doubleclerclage is developed with a wide physiological reconstruction of the cervix and its occlusion mechanism at the inner and outer cervix. We show an alternative to previous surgical techniques that makes a prolongation of the pregnancy possible and causes additionally because of the minimal surgical procedure no disadvantage for the cervical function in coming pregnancies. Small surgical strain, quick surgical procedure and simultaneously continue of diagnostic possibilities as well as the reconstructive technique with small trauma of the cervical tissue are the advantages of this method. PMID- 1413948 TI - Quality of life in long-term survivors of orthotopic heart transplantation. AB - This study was designed to evaluate quality of life and life changes after heart transplantation in long-term survivors, to compare the patients' results with those obtained from healthy subjects of similar age, and to correlate quality of life with psychological and clinical variables. Questionnaires were mailed to all 43 adult German-speaking transplant patients operated between 1982 and 1986. Forty-one (95%) of this patient population completed the questionnaires; 52 controls answered those questions not addressing transplant-specific issues. 83% of the transplant patients versus 88% of the controls rated global quality of life as "good" or "excellent". Psychological affect and well-being were comparable in both groups. 70% of the transplant patients versus only 30% of the controls stated "to be bothered by symptoms". Despite that response, heart transplant recipients perceived postoperative life changes mostly as positive, although sexual function and professional situation had worsened in 34% and 41%, respectively. Global quality of life correlated best with job satisfaction (r = 0.65, p less than 0.01), satisfaction about health (r = 0.64, p less than 0.01), well being (r = 0.53, p less than 0.01), and everyday life function (r = 0.53, p less than 0.01), and correlated negatively with depression (r = -0.40) and physical symptoms (r = -0.36). The study shows that the subjective quality of life of long-term survivors after heart transplantation is similar to that of healthy individuals of the same age group. Thus, survival is certainly not the only indicator of success; aspects of quality of life must also be included in cost effectiveness and/or cost benefit considerations in transplantation policies. PMID- 1413949 TI - [Electrocardiographic diagnosis of acute graft rejection after heart transplantation]. AB - In order to evaluate the diagnostic value of standard-ECG (ST-ECG) and precordial mapping-ECG with 63 unipolar leads (PM-ECG) for detection of acute cardiac allograft rejection, 15 patients (12 male, 3 female; age range 24-64 years) were studied. ST-ECG and PM-ECG were recorded along with 94 endomyocardial biopsies. Twenty-four acute rejections were detected histologically. Using the ST-ECG, a reduction of the QRS-amplitude-sum (lead I, II, III, V1 and V6) greater than or equal to 5% in comparison with the ECG obtained 1 week before was found to be the best diagnostic criterion (sensitivity 63%, specificity 74%, positive predictive value 48%, negative predictive value 85%). By analysing the PM-ECG a drop of the QRS-amplitude greater than or equal to 12% in greater than or equal to 14/63 precordial leads was determined to be the most reliable parameter (sensitivity 79%, specificity 71%, positive predictive value 49%, negative predictive value 91%). In contrast to the high sensitivity of PM-ECG, ST-ECG was less suitable for detection of acute rejection. However, taking into account the high negative predictive value of PM-ECG, acute rejection could be excluded with high probability, if the QRS-amplitudes of the PM-ECG remained stable. This may lead to a lower frequency of routinely performed endomyocardial biopsies. PMID- 1413950 TI - [Magnetic resonance tomography image of transmural myocardial infarct in comparison with 99mTc-methoxyisobutylisonitrile SPECT]. AB - To assess the ability of magnetic resonance imaging (MRI) to identify morphologic and functional abnormalities associated with transmural anterior and inferior myocardial infarction, 18 patients with anterior myocardial infarcts and 11 patients with inferior myocardial infarcts confirmed by ECG and cine ventriculography underwent gradient-echo MRI of transverse and short-axis imaging planes. Myocardial perfusion of corresponding imaging planes was measured by 99mTc-methoxyisobutyl-isonitrile single-photon emission computed tomography (MIBI SPECT). Transmural scar by MRI was defined as diastolic wall thickness 2.5 SD below corresponding normal values of a healthy control group (n = 21). MIBI-SPECT scar was defined as a MIBI uptake less than 2.5 SD below mean values of a healthy control group (n = 11). By MIBI-SPECT, 231 segments contained normal tissue and 161 contained scarred myocardium. In 352/392 (90%) segments gradings based on diastolic wall thickness and MIBI-SPECT gradings were identical. Diastolic wall thickness was significantly higher in normal than in scarred MIBI-SPECT segments (10.3 +/- 1.5 vs 5.2 +/- 2 mm, p less than 0.0001). Additionally, normal segments by MIBI-SPECT showed significantly higher systolic wall thickening than scar segments (5.5 +/- 1.5 vs 0.6 +/- 1.6 mm, p less than 0.0001). The correlation between MRI and MIBI-SPECT assessed infarct size was r = 0.91 for anterior and r = 0.77 for inferior myocardial infarcts. The agreement between MIBI-SPECT perfusion defect size and regions with reduced diastolic wall thickness on MRI tomograms was significantly better for anterior myocardial infarcts than for inferior myocardial infarcts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413951 TI - [Indium-111 or Tc-99m-HMPAO marked granulocytes as specific markers of florid stage endocarditis--results comparing clinical, histological and scintigraphic findings in 30 patients with suspected endocarditis]. AB - Thirty patients with clinically suspected infective endocarditis were scanned with Indium-111- or Tc-99m-HM-PAO-labeled granulocytes. The scans were correlated with the clinical course, and in 20 cases with the results from histologic examination of the valves. In six cases the scintigraphic examination gave correct positive results, in three cases false negative, in one case a false positive, and in 20 cases correct negative results. If we limit the analysis to only the histologically proven cases, our data suggest a specificity of the method of 86% and a sensitivity of about 67%. PMID- 1413952 TI - [Initial clinical trial of a multi-planar transesophageal echoscope]. AB - The prototype of a multiplanar transesophageal echocardiographic transducer was evaluated clinically. This 5 MHz, phased array, 64-element transducer allows to continuously rotate the imaging plane from the transverse (0 degree) position to a maximal 180 degrees position, thus encompassing transverse, longitudinal, and every intermediate position. The transducer is incorporated in the echoscope tip measuring 16 by 11 by 40 mm. The shaft of the instrument is 110-cm long and has a 9-mm diameter. The instrument has pulsed wave, continuous wave, and color Doppler capabilities. 176 clinical patients were examined with the multiplane transducer. No complications occurred. Advantages of this transducer included: 1) comprehensive scanning of the whole mitral circumference and mitral valve; 2) quick and precise alignment of aortic valve long and short axis views, including long axis views of the ascending aorta, with a mean visualized length of 6 cm; 3) improved imaging and evaluation of transvalvular and paravalvular regurgitant jets in mitral and aortic valve prostheses; 4) complete evaluation of all left ventricular segments using multiple planes from transgastric and transesophageal transducer positions. An important potential application is three-dimensional reconstruction of cardiac structures and color Doppler jets. PMID- 1413953 TI - [Morphology of aortic isthmus stenosis--invasive study using intravascular ultrasound]. AB - In patients with coarctation of the aorta, intravascular ultrasound can yield important additional diagnostic information concerning stenosis morphology and aortic wall structure that, thus far cannot be obtained with conventional angiography. For the first time, we were able to visualize, in vivo, the eccentric thickening of the posterior aortic wall, which is the typical morphological finding in patients with coarctation of the aorta, known from post mortem or intraoperative specimens. The additional information about stenosis morphology and aortic wall structure, obtained with intravascular ultrasound, is especially valuable for the newer interventional therapy of balloon angioplasty. With intravascular ultrasound, not only the direct quantitative assessment of the aortic cross-sectional luminal area, but also the immediate visualization of local dissections and aneurysms is possible. Using special angioplasty catheters with integrated ultrasonic crystals (which are currently under manufacturing development), a step-wise dilation with immediate evaluation of the therapeutical success may improve the short- and long-term results of balloon angioplasty. At present, intravascular ultrasound is still only an additional diagnostic tool. If it is combined with interventional balloon angioplasty, however, it could gain increasing clinical importance for the treatment of aortic coarctation in the near future. PMID- 1413954 TI - [Control of catheters in coronary angiography--resistance to torsion in the aortic arch]. AB - A curved catheter, unlike a straight catheter, cannot be rotated around its longitudinal axis without resistance. In a curved catheter section, the torsion causes internal deformation of the material which consumes energy and which is associated with resistance to rotation. This resistance can be measured in terms of a moment of torsion (Nm); it greatly differs in magnitude depending on the cross-section of the catheter and on the catheter material. This resistance to rotation must always be reckoned with in transfemoral coronary angiography, as a consequence of the semicircular curvature of the catheter. The controllability of the catheter therefore does not depend solely on its (likewise measurable) torsional stability, but rather on the ratio between the torsional stability and resistance to rotation in the aortic arch. In the 20 catheter types of caliber 7F, 6F, and 5.2F investigated, the corresponding measurement results were the most favorable for 6F braided nylon catheters. PMID- 1413955 TI - [Complications during directional coronary atherectomy (DCA): catheter fracture between housing assembly and shaft point with subsequent vascular occlusion]. AB - Directional coronary atherectomy of a severe stenosis of the left anterior descending coronary artery was complicated by device fracture between the cylindric housing portion and the distal nose-cone collecting chamber. After successful removal of the DCA device, an early occlusion of the coronary vessel occurred, which could be successfully treated by perfusion balloon catheter. PMID- 1413957 TI - [Abstracts of the autumn meeting of the German Society for Cardiac and Circulatory Research. 15-17 October 1992, Dresden. Abstracts]. PMID- 1413956 TI - [Dysplastic intramyocardial arteries with subaortic septum in patients with hypertrophic obstructive cardiomyopathy]. AB - Abnormal, dysplastic intramyocardial arteries were reported in autopsied hearts of hypertrophic cardiomyopathy. To elucidate their significance, the operatively excised myectomy specimens of 24 patients with hypertrophic-obstructive cardiomyopathy (HOCM), of 18 patients with valvular aortic stenosis and of 10 postmortem normal hearts were investigated. Eight patients with HOCM had dysplastic intramyocardial arteries (greater than 100 microns external diameter) as well as dysplastic arterioles (less than 100 microns external diameter). The value of the scores for the thickness and fibroelastosis of the media was nearly doubled, the tunica intima was frequently thickened, and the lumen was relatively reduced in dysplastic vessels. Neither in controls nor in aortic stenosis dysplastic arteries were found. Volume density of patchy fibrosis (scars) was increased in patients with dysplastic arterial vessels (HOCM II) (7.2 +/- 4.4 Vv%) (p less than or equal to 0.05) as compared with HOCM without dysplastic vessels (HOCM I) (0.8 +/- 2.3 Vv%), with aortic stenosis (0.9 +/- 1.6 Vv%) or with controls (0 Vv%), Patients with HOCM II were significantly (p less than or equal to 0.05) younger (30 +/- 13 years) than those with HOCM I (53 +/- 12 years), aortic stenosis (56 +/- 12 years), or controls (63 +/- 21 years). The anterior septum was significantly thicker in HOCM II (29 +/- 7 mm) than in HOCM I (22 +/- 4 mm), in aortic stenosis (19 +/- 3 mm), or in controls (12 +/- 2 mm). Syncopes were complained by about 75% (6/8) of patients in HOCM II, by 54% (9/16) in HOCM I, and by 44% (8/18) in aortic stenosis (not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1413958 TI - [Geriatric rehabilitation]. PMID- 1413959 TI - [The role of geriatrics in medicine]. PMID- 1413960 TI - [Legal aspects of geriatric rehabilitation]. AB - Nowadays geriatric rehabilitation is recognized as a matter of social law performance. Nevertheless there are very small chances to realize corresponding legal claims in view of the infra-structural deficits. This subscription works out the claims of social law for geriatric rehabilitation, names questions of delineation between illness, prevention and care indigence and discusses problems of geriatric rehabilitant institutions and services. PMID- 1413961 TI - [The rehabilitation potential of the elderly]. AB - This contribution points to the existence of potentials for rehabilitation in the elderly and underlines the necessity of rehabilitation in chronically ill patients. Especially important for the success of rehabilitation is a differential diagnosis and treatment. The potentials for rehabilitation differ among the several functions, abilities, and skills. For this reason, a differential profile of the rehabilitation potentials is necessary. Theoretical and empirical contributions to the plasticity, to developmental potentials, and to competence in the elderly form the basis for prognosis of rehabilitation potentials in old age. It is made clear that realizing these potentials is not only a task of the patient, but is also dependent on the ecological and social environment. PMID- 1413962 TI - [20 years geriatric rehabilitation at the Hannover at the Henrietta Foundation]. AB - This report includes the historical formation of the institution in regard to the background of the development of the German Society of Gerontology. A description of the newly formed clinic and its special institute for geriatric rehabilitation is supposed to provide a survey about the conditions of clinical work as well as the special courses and training possibilities. This is followed by the presentation of treatment methods and results. PMID- 1413963 TI - [The dynamics of aging and rehabilitation following coronary bypass operation]. AB - The dynamics of aging encompass the topics "aging of society" and "coping with chronic illness". Both are discussed using data from a qualitative study on return to work after coronary artery bypass surgery. Data from the retrospective substudy reveal four forms of aging as biographical development toward early retirement, old-age retirement, or related stages. It emerges that the manner of aging is less influenced by medical rehabilitation or medical history, and more by the patient's occupation and socio-economic status. Case reports are used to show that social class is a facilitation context, but not a determining force, regarding the choice between postoperative retirement or return to work. The final section briefly discusses whether the findings concerning the dynamics of aging of the cohort operated on in the late 1970s apply also to that of the cohort operated on in the late 1980s; this is addressed using some data from the prospective sub-study. PMID- 1413965 TI - [The role of nursing care in geriatric rehabilitation]. AB - This article intends to present goals, tasks and focus points in different kinds of institutions of geriatric rehabilitation. This is be done under the aspects of: 1. Accompanying handicappeds during their disease. 2. Nursing orientated of activities in daily life. 3. Nursing with a multiprofessional team and its role within the rehabilitative concept. Besides this, goals and development strategies in professional nursing will be worked out. PMID- 1413964 TI - [Neuropsychological therapy at the computer with the elderly]. AB - Since the end of the 1970s, computers have been used in neuropsychological rehabilitation. This article points out the possibilities, as well as the limits in using computers with the elderly, and is focused on their particular needs. Furthermore, indications are listed whereby computers in neuropsychological therapy in Albertinen-Haus, Hamburg, FRG, have been applied. The need for a neuropsychological diagnostic is shown and illustrated with test examples. Finally, four individual case studies are discussed. PMID- 1413966 TI - Falls and lying helpless in the elderly. AB - Twelve percent of men and 19% of women aged 65 years and over who sought medical attention after a fall, lie where they fell for 15 min or more after falling. The occurrence of a fall with a long period of lying helpless was associated in bivariate analyses with severe injury, an intrinsic or unknown mechanism of falling, falling indoors, poor functional capacity, use of walking aids, body temperature 37.5 degrees C or over, and serum potassium concentration under 3.5 mmol/l. A log-linear model showed that a fall with a lie of this kind was related independently to high body temperature, low serum potassium concentration, and severe injury. The occurrence of such a fall due to an extrinsic mechanism was related to poor functional capacity, but no similar relationship could be found when the fall was due to an intrinsic or unknown mechanism. PMID- 1413967 TI - [Current classification of primary malignant bone tumors]. AB - The classification of primary malignant bone tumors has to include: 1. Histologic diagnosis, iusing immunohistochemistry especially in small-round- and spindle cell tumors. 2. Grading of malignancy, iusing proliferation factors. 3. Definition of compartmentalisation. 4. Staging. Only when all these factors are defined it is possible to plan the best therapy, to compare the results of different centers and to overwork it scientifically. Investigation of chromosomes, oncogenes, chemotherapy resistance a.o. are to be added for classification in next future. PMID- 1413969 TI - [Imaging procedures in diagnosis of bone tumor]. AB - The historical development of the various imaging procedures for diagnosis, differential diagnosis and for the effect of chemotherapy of malignant bone lesions are discussed. The present status of imaging including MRT has been defined. PMID- 1413968 TI - [Osteosarcoma]. AB - Osteosarcoma includes several distinct varieties. It is therefore essential to rely upon a very specialized pathologist. It is necessary to stage the tumor and to histologically define the oncologic quality of the surgical removal (surgical margins). The limb salvage surgery in osteosarcoma involves several areas of risk: the biopsy, the extension of the tumor in the marrow spaces and canal, the impingement or plugging of the vessels by the tumor, the invasion of the joint tissues, the contamination of the joint space and/or soft tissue compartments. The reconstruction after bone segmental resection involves many problems, including long-lasting prostheses, bone bank, microsurgical techniques--the preoperative chemotherapy dramatically reduced the need for amputation, in favour of conservative surgery. A good response to chemotherapy (almost total necrosis of the tumor), is the most important factor correlated with a favorable prognosis. The more recent protocols aim to increase the tumor response and the survival rate through a very intense primary chemotherapy, using Adriamycin, high dose Methotrexate, Cisplatin and Ifosfamide. PMID- 1413970 TI - [Legal evaluation of bone tumors]. AB - Three topics are of major importance in the legal evaluation of bone tumors: The questions of medical liability, of causality and of medical evaluation. Concerning medical liability, the legal consequences of proven cases of malpractice are stressed. A causal connection between an accused trauma and the occurrence of a malignant bone tumor can be denied in nearly all circumstances. Due to the well known occurrence of a secondary sarcoma, the irradiation of a benign bone tumor or tumorlike lesion is strongly disfavored. In cases of medical evaluation, patients with malignant bone tumors should be judged by the same criteria as patients with any other diseases and impairments. PMID- 1413971 TI - [Technique and tactics of biopsy including puncture]. AB - The biopsy is the key for the exact diagnosis of bone and soft tissue sarcomas. However the biopsy implicates risks that eventually may significantly interfere with the prognosis. The steps of the biopsy can be differentiated in tactical and technical aspects. Tactical aspects include laboratory examinations (e.g. blood count, immunological, chemical tests) in order to establish the prebiopsy differential diagnosis, basic imaging procedures (bone scan, magnetic resonance imaging) and to discuss with the pathologist questions as which region of the tumor might be most informative, how should the material be preserved and whether a frozen section might be useful and allow for initiation of therapy as early as possible. Furthermore the site of the biopsy has to be carefully chosen, the compartments that need being passed through or opened up during biopsy must be considered. The technical aspects refer to the approach and tissue handling during the biopsy itself. Fine needle aspiration allows only for a cytologic, core biopsies for a histologic examination (however only of a small sample), while the open biopsy provides more material for more analyses. Any biopsy (open biopsy as well as percutaneous puncture) contaminates the path with tumor cells and increases the risk of systemic seeding. In order to keep these risks as small as possible the most careful technique and tissue handling is mandatory. The biopsy path has to be completely ('en bloc') resected later for local tumor control. PMID- 1413972 TI - [Differentiation of osteogenetic cells: systems and regulators]. AB - Bone formation comprises a complex but ordered sequence of events, beginning with the proliferation of chondrogenic and osteogenic precursor cells followed by their subsequent differentiation, ultimately leading to extracellular matrix maturation and mineralisation. Several models have been established which recreate discrete elements of this network. Factors induce ectopic bone formation, when implanted into muscle pouches, have been characterized as members of the TGF-beta-superfamily. Detailed information about the course of OB differentiation has been obtained from an in vitro model system. The process of mineralisation was found to consist of three distinct time periods: a proliferative phase, a period of extracellular matrix maturation and mineralisation. The development of each states depends on each other. This model is not as complex as the whole organ and cannot of course lead to any conclusion about the kinetic differentiation path of a cell in its normal spatial environment. Different organ culture systems are described and through the application of sensitive methods the differentiation can be studied in the normal spatial environment. The cascade of events in the differentiation process must be strictly regulated. Hormones and growth factors in many cases show a bone-forming and/or bone-resorbing action. The effects of the classical calcium regulating hormones Vitamin D and PTH on OB-differentiation are reviewed. A large number of growth factors have been shown to effect OB. Growth factors, that have been isolated from the bone matrix are of particular interest to bone formation. PMID- 1413973 TI - [Chemotherapy of osteosarcoma]. AB - Intensified adjuvant chemotherapy increased the 4-year metastasis-free survival probability from 50% (COSS-77) to roughly 80% (COSS-86). Preoperative chemotherapy was found without recognizable hazard and promoting conservative surgery. Following resection the local failure rate ist significantly higher than after demolitive procedures, including rotation plasty (10.5% vs. 2.5%). Local failures bare a very poor prognosis (19/23 DOD). The acute therapy related mortality is less than 3%. Late toxicities like ototoxicity and cardiotoxicity are intriguing and deserve increased attention. The management of the osteosarcoma patient is a complex and difficult interdisciplinary task which is best performed in centers experienced in the treatment of malignant musculo skeletal tumors. PMID- 1413974 TI - [KMFTR (Kotz Modular Femur Tibia Reconstruction System) modular tumor endoprosthesis system for the lower extremity]. AB - 206 patients with tumorendoprosteses of the KMFTR-type at the lower extremity were operated at the Institute Rizolli Bologna and at the University Clinic of Vienna. The minimum follow up was 2 years (mean 3.2, max. 8 years). In order to bridge the defect caused by tumor resection the proximal femur was replaced in 42 cases, the distal femur in 119 cases and in 6 patients a total femur prosthesis was used. The proximal tibia was replaced in 35 cases and in 4 cases a total knee prosthesis was implanted. Clinical evaluation according to Enneking revealed 71.6% excellent and good results. In 83.4% the radiological score was higher then 20. We saw deep infections in 8.2% (17 patients), breakage of the prosthesis in 6.8% and aseptic loosening in 5.8%. 3 patients had to be amputated due to infection. In the remaining cases of infection in 66% of the patients healing was observed. All cases of aseptic loosening or breakage could be revised successfully by an exchange of the prostheses and therefore salvage of the leg was achieved. PMID- 1413975 TI - [Psychological adjustment to invasive surgical and medicamentous tumor treatment of osteosarcoma patients with rotation-plasty]. AB - Ten patients with osteosarcomas and rotation plasties made themselves available for a psychological survey. The time elapsed after their operations was between two and ten years, giving an average of six years. All patients were free of tumours at the time of the follow-up examination. Both in personal interviews and in psychological tests, it was possible to observe a very positive development of these patients' attitudes. Contributory factors in this context were discussions with the doctors administering treatment, the cheerful atmosphere of the hospital and the nursing staff, the physicotherapists and ergotherapists, and the excellent social support which all those interviewed also received from their relatives. Continuous positive motivation, a favourable social dialogue and patients' ability to control their own lives would appear to be the key factors in helping patients to come to terms with their illness. PMID- 1413976 TI - [Metal-metal total prosthesis of the hip joint: back to the future]. AB - Late loosening in total-hip-replacement is explained by a foreign body reaction of the connective tissue along the bone-implant interface due to polyethylene debris. In contrast, metal-metal-prostheses, implanted in the sixties, may still today work perfectly without any signs of osteolysis along the bone-cement interface, proving, that metal-metal-pairing is superior to prostheses with polyethylene cups and that cement-anchorage may also be adequate for fixation. A new metal-metal-total hip-joint is presented, that has been implanted from 1988 1990 62 times. PMID- 1413977 TI - [Mobility of patients with coxarthrosis]. AB - The common methods of evaluating walking capacity of patients with osteoarthritis of the hip reported in literature are all inaccurate and are based on symptoms. It has been proved, that these informations are to uncertain and therefore have to be replaced by objective criterias. A method of assessment was developed which can easily be applied in clinical routine without great apparative means. With a pedometer and a stopwatch the time can be measured which the patient needs to pass a distance of 30 meters as quick as possible (MAX 30). Similarly the maximal walking distance (MAX DIST) is evaluated as well as the average walking distance (MEDIAN). It could be shown, that walking capacity is not dependent on the amount of degenerative changes, duration of hip disease and hip motion. Walking capacity is negatively influenced by pain, muscle atrophy and lack of training. Patients with osteoarthritis of the hip are able to walk on average 3 km without interruption, thereby they develop a speed of 4 km/h on average. So they are not much slower than healthy subjects. The two must important aims of conservative treatment of hip disease must be alleviation of pain and improvement of muscular strength. Main indication criterium for hip replacement is walking capacity, not the radiological assessed amount of degenerative changes. PMID- 1413978 TI - [Results 2 to 5 years after implantation of the cement-free "APS" total knee prosthesis. A retrospective study of the first 160 cases]. AB - One hundred-and-forty-seven out of 160 cementless APS total knees replacements have been clinically and radiologically evaluated with a mean follow-up period of 38 (24-60) months. Primary diagnosis has been osteoarthrosis in two thirds and rheumatoid arthritis in one. Reoperations have been performed in 4.9% due to aseptic loosening of the tibial tray, and in 3.7% due to patellar problems (aspetic loosening in 1.2% and luxation in 2.5%). There have been three late infections of the joint leading to arthrodesis in two or exchange operation in one case. The radiologic course of the remaining 126 implants showed excellent or good osseous integration of the implants in more than 80%. We were able to show that rheumatoid arthritis as well as malimplantation of the prosthesis can decrease the rate of osseous integration. PMID- 1413979 TI - [Functional Independence Measure as a predictor of expected rehabilitation outcome in patients with total endoprosthesis replacement and after apoplectic infarct]. AB - Functional Independence Measure (FIM) is a method for uniformly recording functional status in rehabilitation patients. It has been under development in the USA since 1985. In this study, the prognostic value of function tests by FIM on admission to the rehabilitation clinic was investigated in two groups (45 patients in all). Thirty-three patients were admitted for rehabilitation following apoplectic shock, the remaining 12 following treatment of fractures of the femoral neck by total hip replacement. A highly significant correlation was found between the total FIM score on admission and the patient's status on discharge. Of the individual functions studied, the activities "dressing and undressing" and "walking/riding in wheelchair" were found have the highest predictive value. PMID- 1413980 TI - [A modern textbook is 100 years old. Albert Hoffa and the "Textbook of Orthopedic Surgery"]. AB - The appearance of Albert Hoffa's "Textbook book of orthopaedics" in 1891 saw the young special discipline enter a new phase of professionalisation in the German speaking countries. Hoffa defined in this work the scope and methodology of orthopaedics in a sense that is still valid today. By including operative and conservative forms of treatment, he created the foundation for a continued scientific development of the subject. Only with the appearance of Hoffa's work did orthopaedics gain acceptance as a special area by many physicians. The far reaching influence and significance of the textbook for orthopaedics is portrayed with the aid of historic sources. PMID- 1413981 TI - [Isolated systolic hypertension in persons older than 60]. AB - Isolated systolic hypertension (ISH) is generally defined as a systolic pressure of 160 mmHg or more, with a diastolic pressure cut-off point below 95 mmHg in some studies and 90 mmHg in others. Its prevalence and incidence vary from 3 to 30% depending on the definition applied, methodology of measurement, as well as the population and the age and sex of the patients. Mechanisms that could lead to the development of isolated systolic hypertension are discussed, especially the role of atherosclerosis and sodium intake. Comparing results from different countries, the Intersalt study showed that the age related rise in systolic pressure was positively related to the mean sodium excretion in that country. A post-hoc analysis of data from 4 Belgian groups could not show such a correlation within our country. The risks of systolic hypertension on mortality and morbidity in the elderly are considered. The need for further studies to quantify the risk and to establish the effect of treatment is emphasized. Three such studies in patients above the age of 60 years with ISH were started. The studies are double blind, placebo-controlled trials and the main purpose is to examine the influence of treatment on morbidity, mortality, and general well-being. In the American SHEP study the patients of the actively treated group received a diuretic and possibly a beta-blocker or reserpine. The results indicate a significant reduction in non fatal stroke, heart failure and myocardial infarction without a significant reduction in fatal stroke, fatal myocardial infarction, cardiovascular or all cause mortality. Studies in other continents are still in progress, such as the Syst-Chin in China and the Syst-Eur trial in Europe. They may indicate whether the results obtained in the U.S.A. can be extrapolated to other continents and whether the use of other drugs without metabolic disturbances, such as calcium entry blockers and angiotensin converting enzyme inhibitors, produce a similar reduction in events. Additional studies are needed to establish the effect of reducing salt intake in younger age groups on the prevalence of ISH and of the related morbidity and mortality. PMID- 1413982 TI - Maternal diabetes and the effect for the offspring. PMID- 1413983 TI - [Water quality]. AB - The quality of water is more and more important in the polluted world of today. The nephrologist is with his patients a great consumer of water; water for dialysis should be of the highest quality as each maintenance dialysis patient uses up to 150 liters 3 times per week for years, in direct contact with his blood through a very thin dialysis membrane. Water may be polluted at the collection-, treatment- or distribution centers or locally at the place of consumption. Aluminum, chloramine, pesticides, copper, herbicides and many other substances as well as bacteria, may be found in water. For these reasons the nephrologist uses a series of devices to clean or purify the water before use in his dialysis unit: softeners, de-ionisators, reverse-osmosis, charcoal filters, ultraviolet irradiation, a.o. A correct water circuit is important as well, as dead spaces could cause bacterial contamination. The ultra pure water has to be mixed before use in the dialyzer, with a concentrated electrolyte solution. The author discusses all these different aspects of water treatment in the particular situation of hemodialysis. PMID- 1413984 TI - Influence of supplementation with N-3 fatty acids on different coronary risk factors in men--a placebo controlled study. AB - Recent epidemiological studies have shown some beneficial health effects of the long chain (n-3) polyunsaturated fatty acids found in fatty fish. Although the results of these studies are often ambiguous and inconclusive, they have prompted many intervention trials to study the effects of n-3 fatty acids (FA) on the cardiovascular risk profile. However screening of the literature revealed that many of the beneficial effects of fish (oil) were obtained in intervention studies which had several serious shortcomings in their design. Therefore we started a placebo controlled randomised trial with increasing doses of n-3FA (respectively 0; 1.12; 2.24 and 3.37 g n-3 FA/day) and in order to have a maximum compliance this study was done in healthy monks. Fifty eight subjects took the fish oil capsules during 12 months and were thereafter followed for another 6 months. We couldn't detect any effect of n-3 FA supplementation on total cholesterol, HDL cholesterol, LDL cholesterol, apo A1, Lp(a), HbA1C, glucose, fibrinogen, factor VIII, antithrombin III, plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor concentration, on bleeding time or on systolic or diastolic blood pressure. A pronounced significant dose dependent decrease of triglyceride levels was seen, while a slight but statistical significant decrease of apo B levels was observed in the highest fish oil dose. As the importance of triglycerides in the pathogenesis of atherosclerosis is still under discussion, the clinical relevance of these finding is not clear at the moment. It seems therefore improbable that the anti atherosclerotic action of n-3 FA is due to an effect on the lipid, apoprotein, coagulation or fibrinolysis parameters as measured in our study. Hence further research must be focused on other parameters (prostaglandins) which can be influenced by n-3 FA and which probably play an equally important role in the atherosclerotic process. PMID- 1413985 TI - Modulation of the Ca(2+)-sensitivity in phasic and tonic smooth muscle. AB - This work describes the relationship between the cytoplasmic free calcium concentration ([Ca2+]i) measured by the fluorescent Ca(2+)-indicator fura-2, the phosphorylation of the myosin light chain and the force development in the phasic longitudinal smooth muscle layer of guinea-pig ileum and the tonic rabbit pulmonary artery. The close temporal relationship between the rise in cytoplasmic Ca2+ and the initiation of force development as well as the rather good correlation between cytoplasmic Ca2+ and force maintenance leaves little doubt about cytoplasmic Ca2+ being the primary regulator of force. However the present experimental evidence indicate that [Ca2+]i and force are not invariably tightly coupled in smooth muscle. A dissociation between the time course of [Ca2+]i and force was found in the tonic rabbit pulmonary artery but not in the phasic ileum of the guinea-pig. In contrast, there was a pronounced decline in the Ca(2+) sensitivity of the contractile apparatus (desensitization to Ca2+) in the guinea pig ileum during prolonged depolarization, an observation not found in the pulmonary artery. Such desensitization could reflect the activation of highly active myosin light chain phosphatase(s) and the different Ca(2+)-sensitivities of tonic and phasic smooth muscles can, at least in part, be due to differences in myosin light chain kinase/phosphatase activity ratios. The sensitivity of the regulatory/contractile apparatus to Ca2+ was increased by agonists in intact and in permeabilized preparations. Furthermore a different sensitizing potentiation between different agonists was observed. The mechanism of the "sensitization" of the contractile response to Ca2+ could act through the activation of the phosphorylation of a protein phosphatase inhibitor, thereby inhibiting the myosin light chain phosphatase. The experiments therefore show that different levels of tension may be present at the same [Ca2+]i and indicate that the Ca(2+) sensitivity can be modulated in smooth muscle. PMID- 1413986 TI - [The neonatal form of Bartter's syndrome: current findings in etiology and physiopathology]. AB - I. Time has come to distinguish "Bartter syndrome" from "Bartter disease". The latter is an autosomal recessive renal tubulopathy which manifests itself mostly during infancy and childhood. II. Bartter disease is caused neither by a primary renal potassium loss nor by a primary renal hyperprostaglandinism. All evidence is in favor of a defect in the chloride pump located at the thick ascending limb of Henle's loop. III. The most severe expression of Bartter disease is its neonatal form which is characterized by polyhydramnios, premature delivery and a life threatening sodium chloride loss during the early weeks of life. It takes several weeks before sodium wasting turns into renal potassium wasting. IV. Polyhydramnios not associated with echographically detectable fetal malformation is highly suggestive of Bartter disease. Prenatal diagnosis is based on the combination of fetal polyuria and elevated chloride in the amniotic fluid. V. In this setting the administration of indomethacin is useless and even dangerous from the 32nd week of gestation on. Similarly, indomethacin should not be given to the newborn Bartter patient for the first weeks and months of life. Treatment at that stage consist mainly of the administration of large amounts of fluid and sodium chloride. VI. Indomethacin can be used as soon as children with Bartter disease stop growing normally and preferably after the age of 18 months when kidney maturation is established. The daily dose should not exceed 2.5 mg/kg body weight. VII. Hypercalciuria is part of (the neonatal form of) Bartter disease and it is so severe that nephrocalcinosis seems to be the rule. This hypercalciuria is the direct consequence of the chloride reabsorption defect in Henle's loop. Research is needed to find an adequate solution to this problem. PMID- 1413987 TI - [Nucleolus organizer regions in pathomorphologic tumor diagnosis]. AB - Morphology and biological behaviour of tumours are closely related to each other and are the main objects of diagnostic tumour pathology. Anaplasia, for example, a well-known cytomorphological criterion of malignancy, is however only an indirect sign of impaired cellular growth control mechanisms. Nowadays, it is a goal of cancer research to investigate these regulatory processes in order to elucidate new diagnostic criteria of malignancy. Silver staining of nucleolar organizer regions (AgNORs) basically meets this new concept. NORs (rDNA) encode for ribosomal RNA and are thus of central importance for the protein synthesis of a cell. Silver stains NOR associated proteins and indicates activated rDNA. Therefore, AgNOR staining covers the proliferative potential of a given cell or a tumour respectively. A prerequisite of reliable application of the AgNOR method to diagnostic tumour pathology is standardization of the technique, which should be based upon scientific results obtained by basic research. Accordingly, in interphasic cells AgNORs are primarily substructures of nucleoli corresponding to the fibrillar centers at the ultrastructural level. This has been shown to be an important criterion to determine the quality of the silver staining reaction. Most artifacts result from inadequate tissue preservation (fixation), unspecific argyrophilic structures and the staining procedure itself. They should either be excluded or--when ever possible--controlled by a proper staining technique, i.e. adjustment to the stainability of every individual specimen. In this respect, digital image analysis proved to be a useful tool. The mean size of AgNORs in small lymphocytes of the same tissue sample is an equivalent of the argyrophilia of a given histological and cytological specimen (internal staining standard). By use of such a standardized staining technique a high diagnostic accuracy is achieved. The proliferative potential of a cell or a tumour can be determined by number, size, staining intensity and distribution of the silver stained dots. In histological tissue sections the quotient of the mean number of AgNORs/cell and the mean area of one AgNOR dot/cell has been shown to be a very sensitive diagnostic parameter. In cytological specimens determination of the total silver stained area per cell is superior to counting of AgNORs simply by eye. Normal and malignant tissue can reliably be discriminated by these morphometric values. In addition, the malignancy potential of the different preneoplastic lesions, e.g. of the urinary bladder, can precisely be described. Flat urothelial lesions with moderate cytological atypia (D2) exhibit AgNOR values in the range of well differentiated papillary carcinomas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1413988 TI - Identification of bent DNA and ARS fragments in the genome of Choristoneura fumiferana nuclear polyhedrosis virus. AB - We identified four CfMNPV DNA fragments with autonomously replicating sequences (ARS) functional in Saccharomyces cerevisiae. A 0.9-kb fragment which, mapped to 54.5 to 55.3 map units within EcoRI HI of the CfMNPV genome, showed the strongest ARS activity of the four. Sequence analysis of this 0.9-kb DNA segment revealed an A+T-rich region separated from a G+C-rich region by 320 bp. Although no sequence matched exactly the ARS core-consensus sequence, 13 near-matches differing by only one or two nucleotides from the core-consensus sequence, were identified. Ten near-matches were clustered within a 105-bp A+T-rich region, and were arranged as inverted repeats. A section of bent DNA structure was predicted within this region. The bent DNA, which showed temperature-dependent retardation during polyacrylamide gel electrophoresis, was unique as its sequence was arranged as a symmetrical 'tilde' (approximately) structure. The second (1.0 kb) and third (1.6 kb) ARS-bearing fragments mapped within EcoRI-E and -B fragments which contain homologous repeat sequences. The fourth (1.5 kb) fragment had the weakest ARS activity and mapped to the EcoRI-D or -B regions of the genome. PMID- 1413989 TI - Transfer of maternal antibodies results in inhibition of specific immune responses in the offspring. AB - A potentially detrimental consequence of maternally transferred antibodies was demonstrated in a mouse model for rabies virus, where pups from rabies virus immune dams showed a decrease in the generation of specific B- and T-cell responses to immunization with rabies virus antigen, resulting in vaccine failures. The degree and duration of the vaccine failures was inversely correlated with the amounts of maternally transferred antibodies, and exceeded the time when maternal antibodies provided reliable protection against a viral challenge. The low responsiveness to vaccination, measured by serum antibody titers and by lymphokine release upon in vitro restimulation of in vivo-primed lymphocytes, was specific for the target virus of the maternal antibodies and was also observed in pups from Sendai virus-immune dams upon vaccination with the homologous virus. In addition, an inhibition of the specific immune responses was demonstrated upon passive immunization of newborn mice with monoclonal antibodies to rabies virus. Although the mechanism(s) that causes the observed inhibition in the offspring of immune dams or in pups that were inoculated with antibodies postnatally is currently unknown, data presented in this manuscript indicate that the observed effect on B- and T-cell responses might not be solely caused by removal of the antigenic load due to residual maternal antibodies. PMID- 1413990 TI - Characterization of rabies virus glycoprotein expressed by recombinant baculovirus. AB - A cDNA of the glycoprotein (G protein) gene of rabies virus Nishigahara strain was cloned and inserted into a baculovirus genome under the control of the polyhedrin promoter. Infection of Spodoptera frugiperda cells with this recombinant virus produced a large quantity of new protein instead of the parental polyhedrin protein. By immunofluorescent and immunoblotting analyses, the recombinant protein was antigenically similar to the authentic G protein. Its molecular mass estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, however, was slightly smaller than that of the authentic one, and this observation was suggested to be due to the difference in glycosylation level between the two G proteins. The recombinant G protein expressed on the cell surface of the insect cells showed a fusion activity at low pH. The fusion activity was inhibited by antiserum against either whole virions or G protein of rabies virus. PMID- 1413991 TI - Increased influenza A virus sialidase activity with N-acetyl-9-O-acetylneuraminic acid-containing substrates resulting from influenza C virus O-acetylesterase action. AB - Influenza virus type C (Johannesburg/1/66) was used as a source for the enzyme O acetylesterase (EC 3.1.1.53) with several natural sialoglycoconjugates as substrates. The resulting products were immediately employed as substrates using influenza virus type A [(Singapore/6/86) (H1N1) or Shanghai/11/87 (H3N2)] as a source for sialidase (neuraminidase, EC 3.2.1.18). A significant increase in the percentage of sialic acid released was found when the O-acetyl group was cleaved by O-acetylesterase activity from certain substrates (bovine submandibular gland mucin, rat serum glycoproteins, human saliva glycoproteins, mouse erythrocyte stroma, chick embryonic brain gangliosides and bovine brain gangliosides). A common feature of all these substrates is that they contain N-acetyl-9-O acetylneuraminic acid residues. By contrast, no significant increase in the release of sialic acid was detected when certain other substrates could not be de O-acetylated by the action of influenza C esterase, either because they lacked O acetylsialic acid (human glycophorin A, alpha 1-acid glycoprotein from human serum, fetuin and porcine submandibular gland mucin) or because the 4-O-acetyl group was scarcely cleaved by the viral O-acetylesterase (equine submandibular gland mucin). The biological significance of these facts is discussed, relative to the infective capacity of influenza C virus. PMID- 1413992 TI - Analysis of relatedness of subgroup A respiratory syncytial viruses isolated worldwide. AB - Respiratory syncytial virus strains (subgroup A) isolated from around the world during the period 1988-1991 were analysed to determine their relatedness. Analysis was by restriction mapping and nucleotide sequencing following amplification of selected regions of the virus genome by polymerase chain reaction (PCR). Twenty-three viruses of subgroup A isolated from cities in temperate regions of the Northern and Southern hemispheres and the tropics during the period 1988-1991 fell into distinct groupings closely related to four of the six lineages defined in analysis of recurrent epidemics within the same city (Birmingham, UK) during the same period. These observations confirm that multiple lineages of RS virus co-circulate locally, and show that very similar viruses are present simultaneously in widely separated countries. PMID- 1413993 TI - The attenuation phenotype conferred by the M gene of the influenza A/Ann Arbor/6/60 cold-adapted virus (H2N2) on the A/Korea/82 (H3N2) reassortant virus results from a gene constellation effect. AB - A single gene reassortant (SGR) virus that derived its M gene from the attenuated influenza A/Ann Arbor/6/60 cold-adapted (CA) donor virus and the remaining genes from the A/Korea/82 (H3N2) wild type (WT) virus (designated A/Korea/82 CA M-SGR) was previously shown to be attenuated in mice, hamsters, ferrets, and humans. The attenuation (ATT) phenotype of this SGR virus could result directly from an altered function of the mutant M gene product of the A/Ann Arbor/6/60 CA virus, which differs from the M gene of the A/Ann Arbor/6/60 WT virus at only one amino acid or, indirectly from a gene constellation effect in which ATT results from an inefficient interaction between the products of the M gene of the A/Ann Arbor/6/60 virus and other genes of the A/Korea/82 virus. Several lines of evidence from the present study are consistent with our interpretation that the ATT phenotype of the A/Korea/82 CA M-SGR results from a gene constellation effect. First, the A/Korea/82 CA M-SGR and an A/Korea/82 SGR containing the A/Ann Arbor/6/60 WT M gene were each restricted in replication in the upper and lower respiratory tract of mice compared with the A/Korea/82 WT virus. Second, an A/Udorn/72 CA M-SGR containing the M gene from the A/Ann Arbor/6/60 CA donor virus in a background of other genes derived from the A/Udorn/72 (H3N2) WT virus was not attenuated in the respiratory tract of mice. These data suggest that the change in the amino acid sequence of the M gene product from the A/Ann Arbor/6/60 WT to CA virus is not responsible for the ATT phenotype of the A/Korea/82 CA M SGR. In addition, evidence of the genetic instability of the A/Korea/82 CA M-SGR is presented, specifically, an extragenic mutation that results in loss of the ATT phenotype. The implications of these findings for the ATT phenotype of the live attenuated reassortant viruses derived from the A/Ann Arbor/6/60 CA donor virus are discussed. PMID- 1413995 TI - Baculovirus expression of the glycoprotein gene of Lassa virus and characterization of the recombinant protein. AB - A recombinant baculovirus was constructed that expresses the glycoprotein gene of Lassa virus (Josiah strain) under the transcriptional control of the polyhedrin promoter. The expressed protein (B-LSGPC) comigrated with the authentic viral glycoprotein as observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), was reactive with monoclonal antibodies (MAbs) in Western blots, and was glycosylated. Although the recombinant protein was not processed into the mature glycoproteins, G1 and G2, it demonstrated reactivity with all known epitopes as measured by indirect immunofluorescence (IFA), and it was immunogenic, eliciting antisera in rabbits that recognized whole virus in IFAs. Regarding future applications to diagnostic assays, the recombinant glycoprotein proved to be an effective substitute for Lassa virus-infected mammalian cells in IFAs and it was able to distinguish sera from several human cases of Lassa fever, against a panel of known negative sera of African origin, in an enzyme immunoassay (EIA). PMID- 1413994 TI - Expression and properties of the V protein in acute measles virus and subacute sclerosing panencephalitis virus strains. AB - Measles virus (MV) inserts one guanosine (G) residue at a specific site in a subpopulation of the mRNA transcribed from the phosphoprotein (P) gene to produce V mRNA. Using an antiserum against the unique carboxyl-terminal region of the predicted V protein, we found that a phosphorylated V protein was expressed in two acute MV strains (Edmonston and Nagahata) and three SSPE virus strains (Biken, Yamagata, and Niigata). The V protein of Biken strain SSPE virus was electrophoretically and antigenically indistinguishable from the V protein of Nagahata strain acute MV, the likely progenitor of the Biken strain. The V protein of these two viruses was not present in the intracellular viral nucleocapsids, but was found only in the cytosolic free protein pool. Pulse-chase experiments failed to show transport of the V protein to the plasma membrane. The V protein was also absent in the extracellular virions. The P protein synthesized from the cloned gene associated with the MV nucleocapsids in vitro, but the V protein had no affinity to the MV nucleocapsids. These results suggest that expression and properties of the V protein are conserved in chronic MV infection. PMID- 1413996 TI - [The synchronization of behavior and individual distances in groups of wild boars (Sus scrofa L.)]. AB - Some ways of synchronization are identified in the wild pig behaviour, which are parallel body orientation, group getting together and away, individual approaching and moving away, sound signals. Parallel synchronization is characteristic for various compact groups, males and females exposing some differences in the synchronization duration and distances. The synchronization is mainly a property of individuals united by common motivation and interests. Each family union, each offspring group have their own peculiarities of synchronization depending on their structure. Synchronization duration and distances vary by season, while within- and between-group distances are different in ages and sexes. Two ways of appearance of special distances are recognized. The synchronization works as a trigger system regulation spatial distribution of individuals and various social functions. PMID- 1413997 TI - Genetic and physical maps of Saccharomyces cerevisiae, Edition 11. PMID- 1413998 TI - [Occurrence of beta-phenylethylamine and its derivatives in cocoa and cocoa products]. AB - 2-Phenylethylamine was extracted from cocoa nibs and chocolates and analysed by coupled gas chromatography-mass spectroscopy. The amine concentration increases in fermentation of cocoa and decreased during roasting and alkalization. Its concentration in chocolates is dependent on non-fat cocoa contents. Previously unreported aldimines were found in cocoa powders, which arise from the condensation of phenylethylamine and aldehydes. The main component of these products is N-phenylmethyl-N-phenylmethylene amine (CAS 3240-95-7). PMID- 1413999 TI - [Determination of polydextrose in food using ion exchange chromatography and pulsed amperometric detection]. AB - A method to determine the synthetic carbohydrate polydextrose, which is used as a bulking agent for the preparation of calorie-reduced foodstuffs, is described. The sample clean-up involves the extraction of polydextrose with water and enzymatic degradation of interfering polysaccharides, such as starch and inulin. The chromatographic system consists of a high-performance anion-exchange column that separates carbohydrates up to molecular weights of 15,000 and pulsed amperometric detection. For unbaked goods recoveries ranged from 94 to 106%, for baked goods recovery rates of 100 to 115% were measured. PMID- 1414000 TI - Social pediatrics: the essence and the vision. PMID- 1414001 TI - Power calculation for cohort studies with improved estimation of expected numbers of deaths. AB - This paper focuses on improving the accuracy of sample size calculations for cohort studies by careful calculation of the expected number of deaths in the population, taking into account either prior information or realistic assumptions about variables which may affect the mortality or incidence. Sometimes small changes in the assumptions can dramatically alter the expected numbers and may necessitate modifications in the design of the study. Possible modification include extension of the follow-up time, and recognition that the real strength of the study may lie in the potential for pooling several similar studies. The problem will be discussed with reference to two examples of occupational cohort studies where differing prior information was available. PMID- 1414002 TI - Case-control studies in pediatric epidemiology: parent surrogates and potential pitfalls of inaccurate and selective recall. AB - The case-control study is quite popular as a study design for exploring associations between risk factors and disease in pediatric epidemiology. Since data concerning exposures to the child are often collected through interviews with parents or other surrogates, researchers should be aware of the opportunities for bias due to inaccurate or incomplete recall. Methods which exist for the control of this problem are presented. These include: the selection of control groups with childhood conditions of similar etiologic uncertainty as the disease being studied; collecting exposure data from both parents; collection of data from children where possible; diligent interviewer training; reviewing clinical records; and use of validity scales. Strengths and weaknesses of these strategies are discussed. PMID- 1414003 TI - AIDS in the 1990s: meeting the challenge. PMID- 1414004 TI - [Prevention of AIDS in homosexuals]. PMID- 1414005 TI - [Quality of data provided by VESKA medical statistics: the case of the fractured proximal femur]. AB - Within the framework of a retrospective study of the incidence of hip fractures in the canton of Vaud (Switzerland), all cases of hip fracture occurring among the resident population in 1986 and treated in the hospitals of the canton were identified from among five different information sources. Relevant data were then extracted from the medical records. At least two sources of information were used to identify cases in each hospital, among them the statistics of the Swiss Hospital Association (VESKA). These statistics were available for 9 of the 18 hospitals in the canton that participated in the study. The number of cases identified from the VESKA statistics was compared to the total number of cases for each hospital. For the 9 hospitals the number of cases in the VESKA statistics was 407, whereas, after having excluded diagnoses that were actually "status after fracture" and double entries, the total for these hospitals was 392, that is 4% less than the VESKA statistics indicate. It is concluded that the VESKA statistics provide a good approximation of the actual number of cases treated in these hospitals, with a tendency to overestimate this number. In order to use these statistics for calculating incidence figures, however, it is imperative that a greater proportion of all hospitals (50% presently in the canton, 35% nationwide) participate in these statistics. PMID- 1414006 TI - [Learning from America?--Managed Health Care, experiences in health cost containment exemplified by Medicaid in Massachusetts, USA]. AB - Managed Health Care is characterized by a number of different control mechanisms aiming at cost containment in health care delivery. The means and consequences of its application are discussed using the approach of the state of Massachusetts to improve care delivery for Medicaid eligibility as an example and unsolved problems are specified. PMID- 1414007 TI - Physical activity and health--continuing focus of interest for epidemiologic research. PMID- 1414008 TI - Leisure time physical activity in Scotland: trends 1987-1991 and the effect of question wording. AB - In this article data collected between 1987 and 1991 is analyzed to identify changes in the proportion of sedentary individuals in Edinburgh and Glasgow. In the primary question, which asked the respondents about physical activity for exercise such as walking, running and swimming, a wording change deleting the prompt to specific activities is taken into consideration. The data were collected by telephone on 13,586 respondents. A considerable decrease in the proportion of sedentary individuals in both cities was observed between 1987 and 1991. This decrease could not be related to changes in specific sporting activities. The change to an unprompted question led to a 14% lower estimate of physical activity. This was almost fully explained by a change in the estimate of the proportion of walkers. Older respondents in particular were affected by the question change. PMID- 1414009 TI - Detrimental effect of alcohol intoxication on severity of injuries in male traffic accident victims: a cross-sectional study. AB - A cross-sectional emergency room study was performed among traffic accident victims aged 16 to 75 years in order to investigate the prevalence of alcohol intoxication (blood alcohol concentration (BAC greater than or equal to 0.8 g/kg) and its potential detrimental effect on injury severity. A BAC greater than or equal to 0.8 g/kg was present in 29% of the male patients. Intoxicated patients had a similar propensity to require inpatient hospital care (65 versus 60%) but had significantly longer hospital stays than the non-intoxicated patients (36 versus 20 days; p less than 0.05), observations which may be explained by the higher prevalence of serious injuries (head and internal injuries) among the intoxicated cohort. This study supports and emphasizes the detrimental effect of alcohol intoxication on the severity of injuries in traffic accident victims, and reinforces the need for further legal and public health measures in preventing alcohol-related traffic accidents. PMID- 1414010 TI - [Disabilities and impairment in activities of daily living as possible risk factors in dementia: prospective study in Basel 1986]. AB - Because of the increasing number of old people in our society more and more dementia cases will be expected. The etiology of dementia is far from being clear. To get some idea about risk factors 4200 participants (on average 60 years old) of the Prospective Basel Study were asked by letter questions about their health and their way of life. One of the hypotheses to be tested is whether or not disabilities or impairments of activities of daily living could be risk factors for dementia. At present only the results of the basic survey can be discussed. Impairments of hearing, of mobility, of cutting toe-nails and of general physical activity were the conditions which were most frequently named. These results of people being mainly healthy with regard to dementia, will make it possible in the future--in contrast to the cross-sectional studies mentioned in the literature--to test the risk of physical disabilities and impairments of activities of daily living for dementia without being confounded by impairments due to dementia. PMID- 1414011 TI - [Prevalence of smoking in hospital personnel and future teachers]. AB - We have surveyed the prevalence of smoking habits and the opinions about it's regulation among 192 students in two different schools (a teachers' and a nursing school) and among 320 employees of the University Hospital of Geneva. Smoking prevalence varies depending on the profession and sex, and remains high considering the level of education of the surveyed population. Among the future school teachers 23% are smokers. In the hospital, the smoking prevalence is 25% in the health professionals and 32% in the administrative and technical staff. As many as 46% of the future nurses are smoking. Obviously much still needs to be done in order to decrease the number of smokers among the health professionals. The majority of the employees questioned, both smokers and non-smokers, were in favor of regulating smoking in the workplace. 91% of the hospital staff, and 86% of the smokers among them, favored a smoke free hospital policy. Restriction of tobacco use in the workplace should be implemented particularly when it is the wish of a majority of employees. PMID- 1414013 TI - AIDS--over a million new infections in eight months. PMID- 1414012 TI - Knowledge of and attitudes towards family planning and early detection of breast and cervical cancer in two female populations in Greece. AB - This paper presents the results of surveys of contraceptive use, the frequency of induced abortions, the use of the Papanicolaou smear test and knowledge about the practice of breast self-examination in two female populations, characterized by a different socioeconomic level. There exist similar trends, as well as some remarkable differences between the two populations. Both of these populations included a high proportion of women who had undergone at least one abortion. Withdrawal and condom use were the most common contraceptive methods. About one third of women of the two populations had had a smear Pap-test carried out during the last year. 53.8% of the women in the population I and a 44.8% of the population II stated that they know how to practice breast self-examination. PMID- 1414014 TI - Editorial choices: to expand or not to expand... PMID- 1414015 TI - A descriptive analysis of articles in the journal of Social and Preventive Medicine (Soz Praventivmed): 1980-1990. AB - This study provides a descriptive image of the work published in Soz Praventivmed between 1980 and 1990, and analyses certain trends. All articles of this period were categorized and recorded in a data base for: language of publication, city of location and affiliation of first author, sponsor (funding body), citation in Medline, regions and population concerned, type of article and subject matter. Over the decade, we note a reduction in the number of articles with a corresponding increase in their page length, and a progressive increase in the number of articles in English when compared with the two principal languages, German (1/2) and French (1/3). A majority of authors have university affiliations. Studies with original results comprise on average 44.6% of all publications, a tendency which gradually decreases over time. The proportion of epidemiological studies, a majority of which are descriptive studies, has increased progressively since 1980. Among the twelve categories of subject matter chosen as indicators some, such as health services research and research on elderly persons, appear more frequently during the first half of the decade, and others, such as heart disease, cancer epidemiology and AIDS, appear during the second half. PMID- 1414016 TI - Measuring discrepancies between knowledge, preoccupation and fear of aids in populations. AB - A simple tool to quantify discrepancies between knowledge, preoccupation and fear regarding hiv and aids is presented. This tool is based on standard questions available in health surveys. Some results using recent Swiss data are presented, and the method is discussed. PMID- 1414017 TI - [Restrictions to smoking at the workplace and smoking habits: a literature review]. AB - Based on a critical review of the literature, we assess the consequences of restrictive smoking policies at the worksite on smoking habits of active smokers. The majority of the fourteen studies reported to date (eleven studies from the United States, one study from Canada, one from Australia and one from the FRG) suggest that restrictive smoking policies might have a major impact on reduction of cigarette smoking and eventual smoking cessation of active smokers. However, most of the studies suffer from serious methodologic limitations, and more stringent scientific investigations should be carried out. Nevertheless, implementation of restrictive smoking policies at the worksite appears to be a reasonable measure of nonsmoker protection, even before definitive evaluation of the impact on smoking behavior of active smokers. Such implementation should take place without discrimination of smokers in the context of comprehensive worksite prevention programs and should be accompanied by thorough scientific evaluation. PMID- 1414018 TI - [Rheumatism epidemiology in Europe]. AB - The article describes the present and potential of the epidemiology of the rheumatic diseases in Europe, considering especially rheumatoid arthritis (rA) and fibromyalgia (FMA). This is preceded by a short review of the history of European rheuma-epidemiology within the past 40 years. In rA European rheumatologists and epidemiologists have made important contributions to a differentiated nosology, longterm follow up studies and prognostication, conceptualization and measurement of outcomes and the analysis of a possibly decreasing incidence and severity of the disease. In an own study we were able to use the 1987 revision of the ARA-criteria and to test their stability over time. Among 11,534 German residents of Hannover, aged 25-74 we identified 58 with clinically proven rA or undifferentiated arthritis (uA), resulting in an estimated true prevalence of 0.83% (prevalence according) to Rome-criteria 0.53%, ARA-criteria 1987 0.33%). 39/58 could be reexamined after an average of 29 months. Only 9 of 25 ARA-1987-positive rAs maintained their nosological status. The actual care of the total group seemed widely inadequate. The Concept of FMA has been developed in Canada (H. Smythe) and in Germany/Switzerland (W. Muller) at about the same time, in Europe under the notion of "generalized tendomyopathie". Whereas the credit for developing and defining FMA-criteria goes entirely to rheumatologists from North America, it is an European privilege to provide first epidemiological data. After Jacobsson's work in Malmo/Sweden we studied in Southern Germany 541 German residents of Bad Sackingen, aged 25-74. We eventually identified 10 subjects with a history of widespread pain, 17+ out of 34 tender points and 2 or less out of 10 control points, giving a minimal FMA prevalence of 1.9% and an estimated true prevalence of 3.0% (95%-Ci 1.6-4.4%). We identified however several nosologic as well as nosographic difficulties, that question the concept of FMA as an exclusively rheumatological disorder within the spectrum of "soft tissue" rheumatism. PMID- 1414019 TI - [Performance appraisal of internal health services]. AB - In the present context of scarce resources, satisfying at best essential needs in the area of health care leads gradually towards a new conception of the management of health services and towards the development of information tools designed to evaluate performance. This paper presents a general framework for that purpose; it can be adapted to more specific and contextual problems. The authors review the difficulties involved in the measure of performance, the basic data required by the methods as well as some indicators that can be derived from their application, all exemplified in a case study. PMID- 1414020 TI - [First time granting of the Helmut Horten Research Award to Richard Doll and Richard Peto]. PMID- 1414021 TI - [Case report: anorexia nervosa in a 10-year-old boy]. AB - A 10-year-old boy was admitted to the Children's Hospital with a 7-month history of disturbed eating behavior and a recent rapid weight loss: During the 24-day hospital stay the boy displayed a characteristic anorectic eating pattern, hyperactivity, anxiety, depression and compulsive behavior. Discharge followed a 4-kg weight gain. During the subsequent 12 months of outpatient care weight gain and eating behavior normalized. The boy's premorbid personality was described as compulsive and difficult. Although his intelligence was above average the boy had spelling problems and inadequate verbal skills. A change to a college-preparatory school and contact with a family with a vegetarian way of life probably precipitated the acute illness. PMID- 1414022 TI - [Correlation between inpatient and ambulatory psychotherapy exemplified by a case of secondary encopresis in preadolescence]. AB - By comparing the in-patient and out-patient psychotherapeutic treatment of a patient with encopresis in early adolescence the authors develop a psychoanalytical understanding of the psychotherapeutic effects which the different settings have on the patient and his parents. In the authors' opinion both forms of therapy supplement each other and promote the patient's development during the course of treatment. PMID- 1414023 TI - [Need for control and anxiety of losing it--reflections on the treatment of anorexia nervosa]. AB - In connection with the symptoms of anorexia nervosa, which are usually based on a fear of losing control over food intake, we describe a therapeutic approach with the following important aims: To reduce patient's fear of loss of control, to free parents from controlling the food intake of their daughter and to establish a framework that provides a good climate for effective family-oriented or individual psychotherapy or both. In patients with anorexia that began early, we recommend starting with family therapy. This can be followed by individual psychotherapy, which is in fact often requested by the patients themselves. PMID- 1414024 TI - [Psychobiological aspects of the origin and therapy of compulsive disorder]. PMID- 1414025 TI - [Psychotherapy with adolescents]. PMID- 1414026 TI - [Significant progress in the genetic origin of Martin-Bell syndrome including diagnostic consequences]. PMID- 1414027 TI - [Nicotine-induced ambulatory stimulant effect and its reverse tolerance]. AB - Nicotine-induced ambulatory stimulant effect and its reverse tolerance produced by daily administration of nicotine in rats were investigated. Nicotine (0.5 and 1.0 mg/kg, sc) increased the ambulatory activity, which was enhanced by the daily administration of nicotine. Although total ambulatory activity and drinking behavior during 20 h (from 13:00 to 9:00) following daily administration of nicotine (1.0 mg/kg, sc) for 7 successive days decreased, these behaviors returned to the control levels after the nicotine-treatment period. Moreover the periods (tau s) of the ambulatory activity and drinking were not changed by daily injections of nicotine (1.0 mg/kg, sc) for 6 successive days. The enhancement of the ambulatory stimulant effect produced by daily injections of nicotine (0.5 mg/kg) was antagonized by mecamylamine (0.2 mg/kg) and haloperidol (0.05, 0.1 and 0.2 mg/kg), which were subcutaneously administered at 20 min before injections of nicotine. These results suggest that the enhancement of nicotine-induced ambulatory stimulant effect by the daily administration of nicotine is concerned with central dopaminergic stimulation through the nicotinic acetylcholine receptor in the rat brain. PMID- 1414028 TI - [A simple method using a maze task for estimating working memory in mice]. AB - Mice were housed in a cage with a T-maze for 7-9 h a day. A watering place was equipped at one end of the maze. At the other end of the maze, the right and left arms each have two exits, one of which leads to the home cage where food is placed, and the other of which leads to the watering place via a bypass. The exit leading to the home cage in either the right or left was alternately closed every two hours. One-way swinging doors were inserted at the entrance to each arm and between each bypass and the watering place. The mice housed in this apparatus acquired the alternation task at 5 s delay on the 6th day. As the delay became longer (5-150 s), correct response rate showed gradual decrease. Scopolamine (0.1 0.4 mg/kg) did not decrease correct response rate at 5 s delay, but did at longer delay (30 s and 60 s). These results suggest that this method is useful in estimating working memory of mice. PMID- 1414029 TI - 5-HT3 receptor antagonists block cocaine- and methamphetamine-induced place preference. AB - The effects of 5-HT3 receptor antagonists, MDL72222 and ICS205-930, on cocaine- and methamphetamine-induced place preference were examined. Cocaine (0.5-4.0 mg/kg, ip) and methamphetamine (0.25-2.0 mg/kg, ip) induced a dose-dependent place preference. The cocaine (4 mg/kg)-induced place preference was blocked by both MDL72222 and ICS205-930 (0.1 mg/kg, ip). On the other hand, the dose (0.1 mg/kg) of 5-HT3 antagonists did not block the methamphetamine (2 mg/kg)-induced place preference, although a higher dose (1.0 mg/kg) of 5-HT3 receptor antagonists did block it. The difference in sensitivity may reflect a difference in attack point in dopaminergic system of these two psychostimulants. Our findings suggest that the rewarding effects of cocaine and methamphetamine may be indirectly regulated by 5-HT3 receptor; cocaine being more sensitive to 5-HT3 receptor antagonists than methamphetamine. PMID- 1414030 TI - [Behavioral assessment of antidepressants (1)--The forced swimming test: a review of its theory and practical application]. AB - Forced swimming test is now widely used as a screening method for antidepressant drugs since it was proposed by Porsolt in 1977. In this article, we at first reviewed its theoretical background and then pointed out various factors which could possibly affect the results. These include the apparatus used for the test (quality and size of cylinder), experimental animals (breeding condition, body weight, age and strain), method of drug administration and evaluation of animal's behavior (criteria for counting the immobility time and those for excluding variety of orienting or escape behaviors, such as jumping, climbing, diving, circling and extended sniffing behaviors). Finally, potential pitfalls and difficulty of the test were discussed based on our own experiences. We concluded that the various factors discussed in this article should be carefully controlled for the pertinent application of the forced swimming test. PMID- 1414031 TI - [Effects of nicotine on circadian rhythm of ambulatory activity and drinking in rats]. AB - Effects of the intake of nicotine solution and/or forced administration of nicotine at a fixed time-of-day on circadian rhythm of ambulatory activity and drinking in rats were observed under various conditions. Rats showed nocturnal pattern under the light-dark cycle (L: D = 12:12, light period 6:00-18:00), and the patterns scarcely altered while the rats were given 150 micrograms/ml of nicotine solution. When a restricted feeding only for 1 h per day (10:00-11:00) was loaded to the rats, the ambulatory activity and drinking appeared in the light period, especially around the feeding time. While rats were given 15-150 micrograms/ml of nicotine solution under the restricted feeding condition, they demonstrated a marked phase-shift in the circadian rhythm in the concentration dependent manner. Rats showed free-running rhythms with tau value of longer than 24 h under the constant red dim light condition (CRDL), and such rhythm was scarcely modified by the intake of nicotine solution of 50-150 micrograms/ml. However, when nicotine (1.5 mg/kg po), but not tap water, was administered at 10:00 every day under the CRDL condition, it also produced phase-shift which was similar to that induced by the nicotine ingestion under the redose of nicotine is administered or taken at a fixed time-of-day. PMID- 1414032 TI - [The threshold lowering effects of chronic treatment with haloperidol on beta carboline derivative-induced tonic convulsion]. AB - To clarify a relationship between dopamine neuron and purine, GABA or benzodiazepine system, we have studied the changes in the threshold of tonic convulsion induced by each antagonist after chronic treatment with haloperidol in mice. Mice were given haloperidol (1 mg/kg, sc) once a day for 19 d and challenged with caffeine (an adenosine receptor antagonist), beta-DMCM (beta carboline derivative: as a benzodiazepine receptor antagonist), picrotoxin (a Cl- channel blocker) or bicuculline (a GABAa receptor antagonist) 30 min, 24 h and 48 h after the last injection of haloperidol. Only the threshold of beta-DMCM induced tonic convulsion was lowered and it was reversed 7 d after the last injection. The beta-DMCM-induced convulsions on 2 d withdrawal were reversed by diazepam (2.5 mg/kg, ip; a benzodiazepine receptor agonist), Ro15-1788 (5.0 mg/kg, ip; as like a benzodiazepine receptor partial agonist), muscimol (2.0 mg/kg, ip; a GABAa receptor agonist) or apomorphine (0.25 and 2.0 mg/kg, ip; a dopamine receptor agonist). These results suggest that the lowering effect of chronic haloperidol on seizure threshold may be involved in the development of tolerance to haloperidol. It may implicate in direct interactions between benzodiazepine and dopamine or GABA systems but may not between dopamine and GABA neurons in development of lowering seizure threshold following chronic haloperidol treatment. PMID- 1414033 TI - [Postsynaptic mechanism of long-term potentiation]. AB - Long-term potentiation (LTP) is an experimental model for memory and learning in higher animals. It is a well-known fact that intracellular rise in Ca2+ is an essential requirement for generation of LTP. Little is known about the synaptic modulation triggered by the intracellular Ca2+ rise, though the involvement of protein kinase C, Ca2+/calmodulin-dependent protein kinase II (CaM KII), and/or calpain are indicated experimentally. For the purpose of making the synaptic change clearer we tried to characterize the substrates for the protein kinases associated with isolated postsynaptic density (PSD)-enriched fractions. Four major groups of substrates for the CaM KII (250 k M(r), 200 k M(r), 180 k M(r), and 140 k M(r)) and one for kinase C (17 k M(r)) were identified. The 250 k M(r) substrate resembled P400 protein, IP3 receptor, in structure. The 17 k M(r) substrate was different from myelin basic protein which was electrophoresed nearly at the same distance. We made an antibody against the 140 k M(r) substrates to obtain biological and physicochemical properties of the protein. We also made an antibody specific to the Thr286-autophosphorylated and autonomous form of CaM KII. The latter antibody is an extremely useful reagent to understand the biological functions of the CaM KII, especially the role of autophosphorylation of the kinase in modulation of the synaptic function such as in LTP. PMID- 1414034 TI - [The pathogenesis of Alzheimer's disease demonstrated by immunocytochemistry with anti-beta-protein antibody]. AB - Alzheimer's disease is the most common cause of dementia in the elderly. The characteristic neuropathologic findings in this disease are neurofibrillary tangles, senile plaques, and often amyloid infiltration of cerebrovascular walls. These lesions are commonly found in the neocortex and hippocampus, and their clinical significance has been highlighted by quantitative studies showing a significant correlation between the numbers of neurofibrillary tangles and senile plaques and the clinical severity of dementia. In 1984, Glenner and Wong isolated a novel protein (termed "beta-protein") from cerebrovascular amyloid of individuals with Alzheimer's disease and adult Down's syndrome. In the following year, Masters et al, using amino acid sequence data, demonstrated that beta protein is also a component of senile plaque amyloid fibrils. Subsequently, this chemical data was supported by light microscopic and electron microscopic immunohistochemical studies showing that cerebrovascular and senile plaque amyloid deposits are reactive to synthetic beta-protein peptide antibodies. In addition, some recent histochemical and immunocytochemical studies have revealed important new information on the pathogenesis of the senile plaque: senile plaques may undergo sequential structural changes. On the basis of the investigation on a series of Down's syndrome cases, an extensive appearance of beta-protein deposits is an early pathologic change in Alzheimer's disease, and the formation of neurofibrillary changes, including tangles, develops at an advanced stage. The availability of beta-protein amino acid sequence data led to the identification of a full-length cDNA clone coding a possible precursor of amyloid beta-protein. However, the origin or function of this beta-protein precursor still remains uncertain. Further studies are required to know the exact pathogenesis of Alzheimer's disease. PMID- 1414035 TI - [Discriminative stimulus properties of D-amphetamine: a neuropharmacological review]. AB - It has been reported that laboratory animals can discriminate the presence of the psychomotor stimulant, D-amphetamine, from a non-drug or another drug condition. Under test conditions, doses lower than the training dose typically result in proportional decreases in D-amphetamine-appropriate responding, that is, dose response curve is obtained. When drugs other than the training drug (D amphetamine) are tested, they produced drug-appropriate responding to the extent that they resemble D-amphetamine (generalization or substitution test). And some antagonists (e.g., chlorpromazine) attenuate the stimulus effects of training drug. In the present review, the attempt to characterize the neuropharmacological characteristics of the discriminative stimulus properties of D-amphetamine is presented. The neural processes due to the transduction of D-amphetamine into stimulus properties may primarily involve central dopaminergic nervous system. Furthermore, drugs that share the discriminative stimulus properties in laboratory animals often produce similar subjective effects in human. PMID- 1414036 TI - [Autoradiography for drug metabolism and pharmacokinetics study]. AB - Since Ullberg presented a macroautoradiograph showing the distribution of 35S benzylpenicillin in rats by use of a commercial X-ray film in 1954, anything besides X-ray film has never been used for macroautoradiography. In the minireview a new type of radiation sensor, "Imaging Plate" (IP), is introduced as a useful sensor as a sensor that is more useful than previous ones. The IP is a photo-stimulable phosphor that can trap and store the radiation energy quantitatively. About 100 times higher sensitivity than any of ordinary X-ray films and very precise quantitativeness are demonstrated by many results reported recently. Simple procedures are herein presented with a few demonstrative examples of macro- and microautoradiography. PMID- 1414037 TI - [Regulation of (-)-sulpiride-induced increase in evoked dopamine release from striatal slices in rat]. AB - The effects of dopamine (DA) agonist and antagonists on (-)-sulpiride-induced increase in electrically evoked DA release from striatal slices of rats were investigated. (-)-Sulpiride at concentrations of 10 nM to 1 microM in the superfusate caused a dose-dependent increase in electrically evoked DA release from the slices. (+)-Sulpiride had little effect on the evoked DA release up to 1 microM. Apomorphine inhibited the electrically evoked DA release which was antagonized by sulpiride. SCH 23390 and forskolin had no effect on the sulpiride induced enhancement of evoked DA release. Pretreatment with the irreversible DA receptor antagonist, N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), caused a significant increase in evoked DA release and prevented the sulpiride induced increase in evoked DA release. These results indicate that the sulpiride induced increase in evoked DA release is due to an antagonism of the activation of DA autoreceptors by endogenously released DA. PMID- 1414038 TI - [Treatment of chronic eosinophilia-myalgia syndrome--effective therapy regimens become evident]. PMID- 1414039 TI - [L-tryptophan-associated chronic eosinophilia-myalgia syndrome treated with cyclosporin]. AB - After 2 weeks of ingestion of 130 g L-Tryptophan a 52 year old female develops an Eosinophilia Myalgia Syndrome with acute onset of deep venous thrombosis of forearm and possible initial cardiac manifestation featuring intermittent sinustachykardia. This is followed by a severe chronic disease (follow-up 15 months) with diffuse scleroderma and sensomotoric polyneuropathia. The deep muscle biopsy-specimen shows mononuclear infiltration of fascia and interstitial myositis with rare eosinophils. A blood eosinophilia (900/ul) occurs only in the initial acute onset of the illness. Plasma level of Kynurenine is significantly high (4000 pmol/ml), collagenneosynthesis is activated (Procollagen type III peptid 0.927 U/ml). No significant clinical improvement was seen with Acathioprine (100 mg/d) and Prednisolon (40-60 mg/d), after treatment with Ciclosporin scleroderma regresses completely, polyneuropathy is persisting. PMID- 1414040 TI - [Data of two years of the comparative study methotrexate/aurothiomalate in 102 patients]. AB - 102 patients (pat.) with active erosive rheumatoid arthritis (RA) with a median disease duration of only 14 months without malalignment or deformities entered a randomized study to compare the effects of 15 mg methotrexate (MTX) and 50 mg gold sodium thiomalate (GST) administered intramuscularly once a week. The study was double blind during the first year and open during the second year. Clinical and laboratory evaluations were made every three months. X-rays of hands, wrists and forefeet in standard a.p.-projection were taken at month 0, 6, 12 and 24. 32 joints were evaluated according to Larsen. 17/52 (MTX) and 21/50 (GST) patients were withdrawn for several reasons. Withdrawals for toxicity were significantly more frequent in the GST group. 35 patients in the MTX group and 26 patients in the GST group were evaluated for efficacy. All clinical parameters, ESR and CRP improved by more than 50% in both groups without significant intergroup difference. The greatest improvement was seen already after six months. An > 50% improvement occurred in 57% of pat. in both groups. The Larsen score (sum of the Larsen grades of 32 joints) deteriorated significantly in both groups during the first six months (MTX = 3.0, GST = +4.3), it remained stable thereafter in the MTX group and decreased in the gold group. The number of erosive joints increased significantly in both groups during the first six months. This increase was slowed down after six months in the MTX group, in the gold group a decrease was seen indicating a healing of erosions. All differences between the groups were not significant, however. CONCLUSION: While tolerability was better with MTX, both drugs were similarly effective in the treatment of RA and slowed down radiologic progression. PMID- 1414041 TI - [3H-thymidine incorporation into chondrocytes of arthritic cartilage]. AB - An autoradiographic investigation was done to characterize cell proliferation in osteoarthrotic cartilage with regard to the formation of clusters. Altogether, 3H thymidine labelled chondrocytes were rarely observed--a labelling index of 0.5/1000 was calculated. One isolated 3H-thymidine labelled mitosis was found. Labelled cells were often encountered in chondrocyte clusters leading to the assumption that an increased proliferation of chondrocytes is the mechanism of cluster formation. PMID- 1414042 TI - [AA-amyloidosis in inflammatory rheumatic diseases. A report of clinical experiences]. AB - A review of the literature on rheumatic diseases with secondary amyloidosis and our diagnostic and therapeutic experiences in 33 own cases were reported. The place of subcutaneous fat biopsy in the diagnosis of secondary amyloidosis was shown included our own results and the corresponding literature. We saw amyloidosis type AA mostly in patients with high disease activity and progressive stage. There is no sure relationship to the duration of the disease. The renal involvement is clinical most significantly and also most frequently. The renal amyloidosis type AA can be influenced therapeutically however only in normal or unimportant restricted renal function. The therapeutic success is not depended on the choice of the long acting antirheumatic drug. The results were discussed in respect with the current literature. PMID- 1414043 TI - [Arthrography of the iliosacral joint]. AB - We anatomically dissected four pelvic bones without damaging any ligaments, and tried to find a dorsal approach to arthrograph the sacroiliac joint. The joint could not be punctured through its proximal two-thirds: on the one hand, because of its overall angulated orientation, on the other hand, because of the significant overhang of the spina iliaca posterior superior, medially, and the impossibility to make further needle corrections through the very strong ligaments. The only possible approach was situated one finger's width medially to the spina iliaca posterior inferior, with the needle directed laterally at an angle of 20 degrees to the horizontal. Only 0.1-0.2 ml of contrast fluid could be injected. The arthrographic information was reduced to only determining the form of the joint; the state of the cartilage and integrity of the capsule could not be assessed. The best image exposure had to be determined individually and for each case under fluoroscopy, with, unfortunately, a certain level of irradiation. In vivo, the puncture of the lower third of the joint is impossible; the concept of "intraarticular injection of the sacroiliac joint" must be abandoned, as this joint can hardly be punctured dorsally. PMID- 1414044 TI - [Systemic lupus erythematosus: therapy and prevention]. PMID- 1414045 TI - [4th International ANCA Workshop and 2d International Symposium on Wegener's granulomatosis and related vasculitis, Lubeck 28-30 May 1992]. PMID- 1414046 TI - [The limits of intensive care medicine]. PMID- 1414047 TI - [Soft tissue sarcoma in adulthood]. AB - Soft tissue sarcomas (STS) represent a heterogenous group of malignant tumors arising in mesenchymal tissue and in the autonomal and peripheral nervous systems. Only 1% of all malignancies in adults are STS. Most of them are localized at the extremities, but they also occur in the abdomen and the thorax as well as at the abdominal and chest wall. They are usually surrounded by a pseudocapsule which contains tumor cells and they can exhibit a discontinuous growth pattern. Macroscopically undetectable branches might grow along given anatomical structures. Thus the whole sarcoma-related anatomic compartment should be judged as tumor-contaminated. The high rate of local failure is often caused by insufficiently extended primary resections. Lymph node metastases are rare. The main prognostic factors are histological grading, tumor size and surgical radicality. Diagnosis of STS is often made at a rather late state of tumor progression often too late for curative therapy. Early histological diagnosis is thus of great importance. The operation aims at the removal of the whole tumor bearing anatomic compartment. Even wide excisions of the sarcoma surrounded by 3 cm of tumor free tissue will lead to at least 60% local recurrencies. Excisions along the pseudocapsule (enucleation) will most likely leave parts of the tumor behind. Insufficient surgical radicality cannot be compensated for by adjuvant therapies. The resection should be carried out without compromises. PMID- 1414048 TI - [The incidence of wound healing disorders in heart surgery]. AB - In a five-year retrospective study we investigated the wound infection rate after median sternotomy in 2805 adult patients on whom elective surgery had been performed with extracorporeal circulation. On the basis of 14,700 apparently relevant data from 101 patients with wound healing disturbances at the sternotomy site, both the significance of predisposing risk profiles and the prevalence of nosocomial pathogens were evaluated. The control group was formed by 100 patients selected at random. The results were checked for statistical significance using the X2 test for alternative characters; the significance level was set at alpha = 5%. The infection rate observed in our group was 3.6%, which was assigned to 5 internally defined degrees of severity. Cases of healing by second intention were caused to 93% by coagulase-negative staphylococci and staphylococcus aureus. Factors leading to a decrease in oxygenation of the wound area (low-output syndrome, rethoracotomy), diabetes, obesity and the duration of wound drainage were accompanied by a significantly more frequent occurrence of wound healing disturbances. On the other hand, perfusion-technical parameters, operation duration, revascularisation techniques (IMA/ACVB), pulmonary conditioned hypoxemias and the end-of-year desinfection usual in our clinic had no influence on wound healing. Seasonal fluctuation of the epidermal microclimate appear to be responsible for the prevalence and virulence of the pathogen strains in the clinic environment. The preventive measures used in cardiosurgical clinics do not yet represent a fully developed prophylaxis against exposure to nosocomial pathogens. PMID- 1414049 TI - [Treatment of type II B open fracture--therapeutic regimen and results]. AB - A consecutive series of 119 type III B compound fractures in 103 patients was treated at the University of Louisville from May 1983 to May 1989. All patients had timely irrigation of their wounds, serial wound debridements, external skeletal stabilization and parenteral systemic antibiotics (penicillin, cefazolin, tobramycin). 96 open fractures were managed with the supplemental local use of tobramycin-PMMA-beads. There were 13.5% wound infections and 10.1% osteomyelitis observed. The additional local antibiotic therapy was of significant (p less than 0.001, p less than 0.025) benefit to lower both infectious complications. The amputation rate was overall 5%, 9.7% for the lower leg. Four patients died due to multiple trauma. PMID- 1414050 TI - [Closing the resection surface in left pancreatic resection with the surgical stapler]. AB - In the present paper a technique is demonstrated wherein the closure of the pancreatic remnant following left pancreatectomy with absorbable staples was performed. The good results with minimal complications recommend this method. PMID- 1414051 TI - [Perioperative treatment in elective colorectal resection in Germany]. AB - The perioperative treatment of patients with elective colorectal resections in 1086 german hospitals was analysed. In 40% of all hospitals preoperative parenteral nutrition was administered. Following resection iv-fluids were administered in every hospital (6.2% hypo-, 72.4% normo-, 18.7% hypercaloric). Systemic chemoprophylaxis with iv-antibiotics was given in 95.4% of all hospitals. Preoperative bowel preparation included orthograde lavage in 86.1% of the hospitals and oral non-resorbable antibiotics were given in 22.5%. 40.1% of all surgeons performed intraoperative testing of colorectal anastomoses and abdominal drains were used on a regular basis in more than 83% of the hospitals. The principles in perioperative treatment of patients with elective colorectal resections are almost identical all over Germany. Minor differences in perioperative treatment occurred in association with localisation, class of hospital, size of surgical department and annual amount of resections. Also differences between clinical practice and results of recent scientific studies can be observed. PMID- 1414052 TI - [Preoperative intestinal lavage with a polyethyleneglycol-containing solution. A prospective randomized study in comparison with Ringer's lactate solution]. AB - Aim of that study was to prove, whether a solution containing polyethyleneglycol (PEG) is more useful in comparison to the normal method using Ringer's-lactate solution for preoperative bowel preparation. METHODS: From January 1990 up to February 1991 we compared in a prospective randomized simple blind study on 110 patients the whole gut solution (Hewitt) to a bowel preparation with PEG (Oralav). RESULTS: The patients, that were prepared in the common way (Ringer's lactate, control group; n = 54) were approximately given the double amount of liquid (9663 ml) as those in the other group (target group; n = 54: 4777 ml). We found no significant differences concerning the electrolytes. Hemoglobin (-1.1 g/dl) and hematocrit (-3.5%) were significantly lower in the control group. Both groups showed a similar frequency of nausea (control group 25% vs target group 34%). Vomiting was mainly found in the control group (20.8% vs 1.9%). Both groups showed comparably good results in bowel cleansing. Between the two groups we found no differences in specific bowel bacterial flora. Characteristic and number of postoperative complications were similar low (5.7 vs 3.8%). CONCLUSIONS: Due to a better compliance by oral application, the lower given amounts of liquid and the equal cleansing effect we prefer the use of the PEG containing solution (Oralav). PMID- 1414053 TI - [Angioarchitecture of the ileum and colon in Crohn disease]. AB - Vascular changes in resected bowels of Crohn's disease were examined angiographically, microangiographically, micro-preparatorily and histologically. The proper angioarchitecture of the small and the large bowel is being destroyed in the course of the ongoing inflammatory process. Dilated capillaries, destruction of the primary angioarchitecture and its replacement by an irregular, partially bizarre pattern of scar vessels with bundling of the unchanged Vasa recta as varying vessel diameters caused by obliterating secondary fibroses can be seen in advanced Crohn's disease. The angioarchitecture of the pseudo-polyps in Crohn's disease is characterized by an increased number of vessels, bizarrely bended vessels and a radial pattern of veins. All these vascular changes in Crohn's disease are to be seen as secondary changes due to the inflammatory reaction. PMID- 1414054 TI - [Puncture catheterization of central veins--experiences from a primary care clinic]. AB - BACKGROUND: We introduced in the years 1984-1989 317 central venous catheters. Our results and conclusions for using those catheters in smaller hospitals are described. MATERIAL AND METHODS: 4 physicians inserted under standardized conditions 317 central venous catheters in the intensive care unit using the transmuscular way for puncturing the V. jugularis interna and the infraclavicular way for puncturing the V. subclavia. RESULTS: Puncturing the V. basilica complications were not registered. By the V. subclavia route a Pneumothorax rate of 1.7% and an arterial puncture rate of 4.1% were found compared with a 4% arterial puncture rate using the V. jugularis interna. We couldn't find the V. subclavia in 3.4% and the V. jugularis interna in 8%. The complication rate decreased with increasing experience of the physicians. The positions of the catheters in the venous system were not appropriate in 46.9% of the cases after puncture of the V. basilica and in 1.3% after puncture of V. subclavia. Wrong catheter positions were not found after puncturing the V. jugularis interna. Complications as thrombophlebitis were observed in 6.5% after puncturing the V. basilica and 1.1% of the cases after V. subclavia puncture. CONCLUSIONS: Central venous catheters can be safely used also in smaller hospitals if applied by a standardized method. A limited team of physicians can get enough experiences also in a slight number of patients, so that complication rates as low as in international statistics were found. PMID- 1414055 TI - [The compartment syndrome with special reference to vascular surgery aspects. A patient sample of the Cologne University Clinic 1981 to 1991]. AB - The compartment syndrome, a well known complication in traumatized patients, is not taken enough notice of in the literature of vascular surgery despite it's obviously important pathophysiological context. Considering arterial occlusive disease the ischemia as well as the reperfusion can increase the compartmental volume respectively the tissue pressure. The subfascial pressure measurement should not lead to a false certainty, since no critical pressure values exist that can serve as a general criterion for diagnosis and treatment. The "thought about it" may be the first step to a clinical diagnosis and subsequent therapy. Decompression of all four compartments at the lower leg by the technique of Matsen represents the therapy of choice for the compartment syndrome of the lower leg. PMID- 1414056 TI - [Serum gastrin level in patients with colorectal adenoma or carcinoma]. AB - During the last years interest has focused on the trophic effect of gastrin in colorectal carcinomas. Some reports indicated an increased serum level of gastrin in patients with colorectal adenomas or carcinomas. In a prospective study in 261 patients submitted to colonoscopy fasting serum gastrin concentrations were determined. 91 patients served as control, 89 patients had one or more adenomas, 55 patients suffered from a colorectal carcinoma, 17 had a benign, postoperative stenosis of the colon, and 9 had a chronic inflammatory bowel disease. All patients fulfilled the following criteria: No regular drug intake, no previous gastric or small bowel operation, no known ulcer disease, no abnormalities in serum calcium, creatinine, triglycerides, cholesterol and blood urea. Mean gastrin level was 86.63 +/- 23.8 pg/ml in the control, 84.57 +/- 25.1 pg/ml in the adenoma group and 84.6 +/- 24.4 pg/ml in the carcinoma group. No difference of serum gastrin levels were observed regarding sex, age, tumor stage and localisation. PMID- 1414057 TI - [Results of surgical therapy of choledocholithiasis--a retrospective study]. AB - A multimodal therapeutic concept of choledocholithiasis with endoscopic and surgical procedures is presented. Between January 1986 and December 1990 106 patients with choledocholithiasis were operated. These patients are retrospectively analyzed. The success rate is 95.3%, the morbidity 18.7% and the mortality 0. These results are compared with the published data of the surgical or endoscopic therapy of the choledocholithiasis. PMID- 1414058 TI - [The arterial blood supply of extrahepatic bile ducts of the donor liver]. AB - The discussion of the etiopathogenesis of biliary complications after orthotopic liver transplantation have always encountered the problem of the status of a limited or interrupted blood supply of the ductus hepatocholedochus in the liver graft. For the description of the arterial vascular anatomy of the common bile duct 40 liver specimen were postmortem explanted and injection replica were made using corrosion technique. The arterial structures were systematically analysed and classified on the basis of their origin, distribution, calibre and combination. As a result, two types of arterial blood supply were defined and conclusions drawn for the surgical dissection during hepatectomy of the graft. PMID- 1414059 TI - [Gunshot and stab injuries of the abdomen]. AB - From 1973 to 1991 a total of 422 patients underwent surgery because of an abdominal trauma. 12 patients had gunshot wounds and 46 patients stab wounds. In a retrospective study the diagnostic and therapeutic procedure and the indication for surgery are analysed. After gunshot wounds of the abdomen we always performed a laparotomy. In 11 od 12 cases we found serious intra-abdominal injuries. Only in one case the laparotomy was "unnecessary", because of a tangential wound without penetrating of the abdominal wall. After stab wounds the diagnostic and therapeutic management was more selective. Indications for mandatory laparotomy after stab wounds were a manifest hemorrhagic shock, evisceration and a still left weapon in the abdomen (n = 22). The first clinical examination was completed by ultrasound or peritoneal lavage. Pathological findings like free intraperitoneal fluid or a positive lavage also were indications for laparotomy (n = 9). The other patients were observed closely, including repeated physical examination. The indication for surgery then based on the development of clinical signs. The time between first examination and laparotomy was never more than 12 hours. 39 patients (84.7%) had injuries of intraabdominal organs. 5 patients (10.8%) had a negative laparotomy. The mortality rate was 3.4%, but there was no death as a result of the selective approach. PMID- 1414060 TI - [Use of the dynamic condylar screw in fractures of the coxal end of the femur- are there advantages in gerontologic traumatology?]. AB - Till now instable fractures of the upper end of the femur were treated by using the 95 degrees fixed angle blade in gerontotraumatology, too. As an alternative treatment within 16 month we used the dynamic condylar screw (DCS) in 87 cases of patients elder than 65 years. The results were compared to 81 patients, who had been treated by implantation of 95 degrees fixed angle blades. As to gerontotraumatology it was interesting, that there were no DCS-specific complications, which demanded operative revision. Advantages of the DCS are easy insertion, firm fixation, increased strength and resistance to stress failure, short times of operation and hospitalisation. The most important disadvantage--as to gerontotraumatology--however is the not existing primarily load capacity. PMID- 1414061 TI - [External torsion fractures of the tibia combined with ankle joint fractures]. AB - The aim of this retrospective study is to emphasize on combined fractures of the tibia with lesions of the ankle joint. The report bases on 820 fractures of the lower leg. 123 cases showed external rotation fractures of the tibia, which were combined with lesions of the ankle joint in 88 cases. 25 patients were operated on the ankle joint. Because of the combination of external rotation fractures with lesions of the ankle joint, which accounted to 65% of the posterior tibial margin, to 17% of the lateral malleolus and to 3% of the syndesmosis, it is important to investigate the ankle joint radiologically and clinically. PMID- 1414062 TI - [What is the best method of contraception?]. PMID- 1414063 TI - [Trichomonas infection in the female and the current status]. PMID- 1414064 TI - [Uterine abnormality and fallopian tube damage--surgical correction in one session?]. AB - From 1983 to 1990 15 metroplasties were carried out at the Department of Obstetrics and Gynecology Greifswald. 11 of these operations were combined with a microsurgical tubal operation. For the diagnostics of uterus malformation and tubal damage as many methods as possible (hysterosalpingography, laparoscopy with chromotubation, hysteroscopy and sonography) should be used. A postoperative life birth rate of 62.5% shows that an operative correction of uterus malformation and tubal damage in one session is justified. Metroplasty is also indicated at primary tubal sterility with simultaneous uterus malformation. A caesarean section is not primarily indicated after metroplasty. PMID- 1414065 TI - The grand multipara--an obstetric problem? AB - At the Medical Central Department of Obstetrics and Gynecology in Sibenik over 1970-1991 period there were 26,116 deliveries (multiple births excluded), of which 254 (0.97%) occurred in grand multiparas (five and more deliveries). The authors have found that the number of grand multiparas decreased by 38.3% (P < 0.001) over the past eleven years. Control subjects were 7920 multiparas (two to four deliveries, 20-34 years of age, from the same period). In 84.3% of the cases grand multiparas were delivered of their fifth or sixth infant, and 68.5% were > or = 35 years of age. Spontaneous abortion occurred in 16.9%, and 14.2% had no antenatal visit. EPH gestosis (8.3%), glucose intolerance (9.9%), preterm delivery (8.3%) and meconium-stained amniotic fluid (15.0%) were more common in the grand multiparas, whereas cervical cerclage (5.4%) and 7-to-12-hour duration of labour (12.8%) were more common in the control group. No significant differences were found in weight gain, prolonged pregnancy, caesarean delivery, assisted breech and vacuum extraction between two groups. There was also no difference in the incidence of neonatal morbidity and congenital abnormalities between the grand multiparas and controls. Late fetal and early neonatal deaths in the grand multiparous and control group occurred in 1.18% and 1.57, respectively, resulting in a 2.75% overall perinatal death rate for both groups (P > 0.05). No case of maternal death or uterine rupture occurred in either group. The authors conclude that pregnancy and delivery in grand multiparas are at higher risk due to poorer antenatal care and advancing maternal age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414066 TI - [Experiences in dealing with tubal sterilization]. AB - The political changes in the GDR and the unity of Germany give the women the possibility of deciding for tubal sterilization as a method of contraception that was restrictively used in the GDR. This investigation analysis the psychosocial and medical factors influencing the women in their decision for sterilization. 103 women were interviewed with a questionnaire before they underwent tubal sterilization in a great medical center in Sachsen-Anhalt. The findings known in the literature regarding the satisfied after sterilization were discussed. However the sterilization is an intervention that should be thought over carefully. PMID- 1414067 TI - [Lupus anticoagulant and antiphospholipid antibody values in a family with systemic lupus erythematosus]. AB - The Lupus Anticoagulant (LA) is an immunoglobulin directed towards the phospholipid portion of the prothrombin activator complex. This immunoglobulin because first identified in the plasma of patients with Systemic Lupus Erythematodes, was named as Lupus Anticoagulant. Although initially described in patients with SLE, it was subsequently observed in other diseases and also in patients without any manifest disease. SLE or similar diseases are present in 35% of LA (+) patients. The LA prevalence in SLE patients has been found as 34% whereas ACA prevalence was found as 44%. While searching for the presence of LA and the levels of APA in cases having unexplained recurrent fetal losses, a family (a mother and 3 daughters) was discovered, whose each member has been diagnosed as SLE at different times and with different symptoms. Data suggesting the presence of LA and high APA levels were determined in all the members of the family and also it was realised that cause who had recurrent fetal losses had the highest APA levels. In addition to immunoassay methods to detect APA, examination of coagulation tests in patients with unexplained thrombosis and/or fetal losses, would be of great help. PMID- 1414068 TI - Acute periappendicitis after an elective section. AB - The diagnosis periappendicitis is well known. The causes to periappendicitis are manifold. In the literature, we have not yet found a case, where periappendicitis developed because amnion fluid passed to the peritoneum during an elective section. We present a case, where a patient, 5 days after an elective section, developed the symptoms of appendicitis. The pathologic diagnosis is periappendicitis, presumably developed because of the amnion fluid. PMID- 1414069 TI - [Factor XIII deficiency: blood coagulation defect in pregnancy]. AB - Rare haemorrhagic disorders cause a lot of diagnostic and therapeutic problems to the obstetrician. By means of a pregnancy course and a birth process a report is given on the physiological drop of the factor XIII serum concentration and its difficult clinical interpretation. This paper presents pathophysiology, symptoms, complications and treatment of factor XIII deficiency in pregnancy. PMID- 1414070 TI - [C-1 esterase inhibitor deficiency as an obstetric problem: a case report]. AB - The present paper reports a case of C-1-esterase-inhibitor-deficiency in pregnancy. After preoperative i.v. application of 500 E-1-esterase the section caesarean was performed. Problems of this disease, relevant for obstetrics have been described. An interdisciplinary cooperation between obstetrics, anaesthetics and dermatologists is important. PMID- 1414071 TI - [Crede's prevention of ophthalmia under discussion]. PMID- 1414072 TI - [Functional aspects of healing in microsurgical tubal anastomosis--experimental studies of the rabbit fallopian tube]. AB - Ovarian function and fertility was studied in 46 female New Zealand White rabbits after isthmic-isthmic reanastomosis of the oviduct. Postoperative ovarian function was slightly suppressed and returned to normal after two month. No significant differences were found between the control side and the side of anastomosis. Fertility was reduced directly after surgery on the side of anastomosis as well as on the control side. On the side of reanastomosis a continuous increase of tubal function occurred up to two month after surgery. At this time tubal function was reduced to 30%, the nidation index was about 0.6. Tubal function of the untreated oviduct was nearly normal (nidation index 0.8) two weeks after surgery. PMID- 1414073 TI - [Ultrasound assessment of the endometrium in early detection of endometrial cancer in high risk patients]. AB - In 300 postmenopausal adipose and complaint-free patients but with one risk factor for the development of endometrial carcinoma one prospective study transabdominal and transvaginal ultrasonographic examinations by 3.75-MHZ abdominal and 5-MHZ vaginal sound was carried out. In all cases with endometrial thickness of 10 mm and also with endometrial thickness of 5-10 mm and irregular endometrial boundary fractional curettage was done. The rate of abnormal findings was 8% of which in 18 patients the findings were histologically confirmed (3 endometrial cancer, 5 hyperplasia, 8 polyp and 2 submucosal myomas). The sensitivity of ultrasonography was found to be 75%. Patients with normal findings were controlled in 6 months, none of these patients showed pathological symptoms. PMID- 1414074 TI - [Organ preserving endosurgery in pyosalpingitis]. AB - Pyosalpinges are a difficult therapeutic problem in a complicated pelvic inflammatory disease. To avoid a diffuse peritonitis, often a laparotomy with salpingectomy is performed. 20 women of reproductive age with a uni- or bilateral pyosalpinx were incorporated in a prospective study to investigate the possibilities of a combined endosurgical/antibiotical treatment. After endoscopic confirmation, the patients were taken into study. During diagnostic laparoscopy, a salpingotomy with rinsing of the tubes and a drainage of the Douglas pouch took place. After one week of antibiotic treatment, a second-look laparoscopy was performed in all patients; no recurrence was documented. The combination of endosurgery and chemotherapy showed to be a safe and efficient therapy of tubal abscesses in women of reproductive age. PMID- 1414075 TI - [Duplicity of Gartner duct cysts--a single case report]. AB - A 44 year old patient has pains over a long period of years. Only surgical removal of residuals of Gartner-duct-system both para-vaginal and sub-urethral could make her painless. PMID- 1414076 TI - [VII. International Congress on Infections in Gynecology and Obstetrics 4-7 March 1992 in Munich]. PMID- 1414077 TI - [I. Symposium of the German-Japanese Society of Gynecologists and Obstetricians 3 April 1992 in Chiba, Japan]. PMID- 1414078 TI - [8th professional workshop of the "Zurich Discussion Circle" April 1992. Recommendations for oral contraception]. PMID- 1414079 TI - Surgery, dopamine agonist therapy of combined treatment--results in prolactinoma patients after a 12 month follow-up. AB - In a non-randomized retrospective study n = 36 prolactinoma patients (n = 7 micro and n = 29 macroadenomas) were evaluated before (E0), 4 (E1) and 52 weeks (E2) after applying 3 different treatment modalities: A dopamine agonist (DA) therapy (n = 14), B surgery as initial procedure (n = 12) and oral DA therapy, C DA preinjection, subsequent surgery (n = 10) and oral DA medication. T0 outline the effect of the 3 regimens upon serum prolactin (PRL) and tumour size reduction, clinical signs and symptoms, anterior/posterior pituitary lobe function and MRI/CT findings were evaluated in each patient at E0, E1 and E2. In group A, PRL normalization was achieved in n = 10 patients (71%), although the frequency of an empty sella was only one out of 12 macroprolactinoma patients (less than 10%). Patients of group C showed the lowest PRLE2 levels (32 +/- 11 ng/ml, normalization rate 60%), although not statistically significant when compared with the other groups (A: 41 +/- 28 ng/ml, B: 114 +/- 33 ng/ml, normalization rate 31%). According to MRI studies in groups B and C total removal was achieved in 33% and 50% of macroprolactinomas, respectively. The most favourable ratio of the leading pre/posttreatment signs and symptoms was observed in patients of group C. It was concluded that no superiority of either treatment regimen exists for prolactinoma patients. Each mode of therapy has its own benefits which may be applied to the different biological behaviour of a prolactinoma in the respective patient. PMID- 1414080 TI - [Delayed onset of postoperative deterioration in clivus chordoma and clivus meningioma]. AB - The starting-point of the presented retrospective, clinical study is the observation, that in some cases a delayed postoperative neurological deterioration develops after removal of great, extraparenchymal, infratentorial brain tumors. Therefore, we evaluated the postoperative clinical course of 50 clivuschordomas and clivusmeningiomas of the Neurosurgical University Clinic in Mainz (Germany). The results obtained show, that 1 of 3 patients develops a delayed, postoperative deterioration. Important factors, which cause that deterioration, are the age of patients and the size of tumors. Mostly, we found a perifocal edema concomitant to the delayed deterioration within the decompressed brain tissue. We call that phenomenon "decompression edema" as a "hypothesis a posteriori", which has to be proven experimentally. PMID- 1414081 TI - [Effects of nimodipine in experimental permanent focal cerebral ischemia]. AB - In a controlled double blind experiment the influence of a continuous i.v. infusion of Nimodipine (1 microgram kg-1 min-1) upon infarct size, histopathology and neurological outcome in rats with permanent middle cerebral artery (MCA) occlusion was examined. The infusion was started 20 min. before the induction of ischemia and continued 4 hours thereafter. The nimodipine treated animals were subdivided into hypotensive (MABP lower than 85 mmHG for more than 5 minutes after arterial occlusion) and normotensive groups. Infarction size, documented by TTC, H&E and Nissl staining was significantly smaller (p less than 0.001) in nimodipine normtonic rats than the lesions in placebo and saline treated rats, as well as compared with hypotonic nimodipine animals (largest infarction). These differences were found to be entirely at the expense of the cortical (frontoparietal) component of the lesion, suggesting "penumbra" action of the drug. Moreover, nimodipine normotonic rats displayed lower cortical neuronal injury in the periinfarct zone. These findings were corroborated by corresponding better neurological scores. Our results indicate that nimodipine is effective in reducing focal cerebral ischemia, provided the MABP is maintained higher than 85 mmHg. PMID- 1414082 TI - [Linear relations of brain pulse amplitude to mean intracranial pressure]. AB - A catheter for intracranial pressure monitoring was introduced into the right lateral ventricle in 71 neurosurgical patients. In 63 patients (88.7%) a significant linear relationship was found between the cerebral pulse amplitude (PA) and the mean intracranial pressure (Pm). In 8 patients (11.3%) no linear relationship was established between PA and Pm. PA- and Pm-analyses performed subsequent to these compliance tests are discussed on the basis of the pathophysiology of the intracranial space. PMID- 1414084 TI - Influence of duration of simulated transport on plasma stress markers in the calf. AB - The effects of simulated transport of calves for 150 min on plasma cortisol, NEFA, glucose, and calcium were evaluated. Both cortisol and NEFA reached maximal values within 30-60 min, with no further increases during the transportation. Changes in glucose and calcium were not significant. The results indicate that in simulated transport, the duration per se is not a crucial factor in transport stress. PMID- 1414083 TI - [Remission of schizophreniform psychosis after brain tumor surgery]. AB - A 19-year-old female was admitted to hospital due to a schizophrenia-like psychosis of the paranoid type including delusions and various hallucinations. Neurologically she only showed tics of the eyebrows with increased eye blinking. 30 months before an astrocytoma located on the left basal temporal lobe had been resected after the patient suffered from several psychomotor and two grand mal seizures. Following post-operative anticonvulsant therapy seizures had completely disappeared and the patient had been free of symptoms of any kind. After the acute onset of the psychosis another follow-up MRI of the brain using coronary sections revealed a small relapse-tumor. Symptoms disappeared after high-dose neuroleptic therapy. Finally another surgical intervention led to a lasting remission of the psychotic symptomatology (so far 18 months). Postoperatively neuroleptics could be discontinued. Clinical picture and MRI findings will be discussed with a focus on possible etiological factors in schizophrenia. PMID- 1414085 TI - [Diagnostic potential of biochemical and cytological parameters in bronchoalveolar lavage fluid in healthy calves and calves with pneumonia]. AB - Bronchoalveolar lavage fluid (LF) was obtained from cranial as well as from caudal regions of the bovine lung in healthy and pneumonic calves. LF was investigated biochemically, cytologically, and bacteriologically. In healthy lungs free of pneumonic lesions, no differences due to the different parts of the lung were established. An increase in both protein content and number of cells and a marked influx of neutrophils were found to be the most important alterations caused by pneumonic lesions. The diagnostic potential of lactate dehydrogenase, alkaline phosphatase and the size of alveolar macrophages in LF was validated. PMID- 1414086 TI - Electrocardiographic findings in calves with experimentally induced right ventricular hypertrophy. AB - Surface electrocardiograms (ECG) from 20 clinically healthy calves and 3 calves with experimentally induced right ventricular hypertrophy (RVH) were studied to assess the influence of RVH on the configuration of the bovine ECG. In the calves with RVH decreased cardiac axes and increased voltages of QRS complexes in leads I and aVL (extremity leads) and in bv1 and bv5 (precordial leads) were found. Using generally accepted human electrocardiographic theories, these findings could be explained from geometrical differences between the hearts of normal calves and the hearts of calves with RVH. PMID- 1414087 TI - Relationship between lactation-associated body weight loss, levels of metabolic and reproductive hormones and weaning-to-oestrous interval in primiparous sows. AB - Twelve conventionally fed primiparous sows with a similar number of piglets were divided into 3 groups (n = 4) according to their body weight loss after a 5-week lactation as follows: H-gr (loss greater than 25 kg), M-gr (loss 11-25 kg) and L gr (loss less than or equal to 10 kg). Blood samples were collected at 9, 12, 15, 18 and 21 h, from 4 days before weaning until 3 days afterwards, and every 15 min for 6 h on the day before and the day after weaning. The group of sows with higher weight loss during lactation tended to have a higher farrowing weight and higher pre-weaning plasma prolactin levels. At weaning, the L-gr sows had higher plasma insulin and lower plasma cortisol concentrations, especially when compared with H-gr sows. Among the ten sows that showed oestrus within 10 days of weaning, no between-group differences were found in the length of the interval from weaning to oestrus. No significant differences between groups were observed in levels of oestradiol-17 beta and LH. The higher level of insulin in L-gr sows might relate to the higher number of corpora lutea observed in this group. PMID- 1414088 TI - Farrowing disorders in the sow: a field study. AB - A prospective study was carried out in three intensive farms. 150 sows were individually followed from 20 days prior to farrowing to 5 days after farrowing. During the five post farrowing days, the prevalences of fever (rectal temperature greater than or equal to 39.8 degrees C), anorexia, vulval discharges and mammary gland disorders were 15.3%, 20%, 64.5% and 3.3% respectively. Parturition duration (piglet delivery) was 197 minutes on average. Farrowing lasted over 300 minutes for 10% of the sows. The 5 parameters were combined to build a score on farrowing disorders. The sows getting the highest rate of disorders tended to show specific physical features prior to farrowing. The oldest sows, the heaviest, those showing urinary infections or locomotor disorders were more predisposed to problems. Moreover affected sows gave birth to larger litters for a given parity. PMID- 1414089 TI - Opioid inhibitory control of the ruminant stomach motility: functional importance of the hypothalamus. AB - In conscious sheep, Leu-enkephalin (10 and 20 micrograms.kg-1) administered into the third cerebral ventricle caused a psychosedative action and a significant inhibition of the frequency of rumen contractions. The amplitude of the first rumen contractions, following immediately after the end of the Leu-enkephalin's infusion (at a dose of 20 micrograms) and the average amplitude of primary rumen contractions were also significantly inhibited. The hypothalamic isolation prevented both the inhibitory effect of Leu-enkephalin on the rumen motility and the drug induced psychosedative action. In contrast, Leu-enkephalin (20 micrograms.kg-1), significantly enhanced phasic contractions of the rumen after hypothalamic isolation. However the hypothalamic isolation did not prevent Leu enkephalin induced inhibition of the mean amplitude of rumen contractions, but this inhibition was not significant (NS). The character of the histopathological changes induced by the isolation of the hypothalamus showed descending degenerative changes of the neuronal pathways connecting the hypothalamus to the pons and lower to the medulla. These results do suggest that the isolation of the hypothalamus causes the degeneration of the descending inhibitory opioid pathways connecting the hypothalamus to the gastric centers of the medulla and point act out the functional importance of descending tonic opioid inhibitory control of ruminant forestomach motility. PMID- 1414090 TI - Bovine vectocardiography: a comparative study relative to the validity of four tridimensional lead systems. AB - For spatial vectocardiography to become applicable for cardiac investigation in cattle, it was necessary to develop a reliable standardized electrocardiographic lead system in this species. In this study, four tridimensional lead systems, initially developed in horses, were compared when applied in calves. Fifty seven electrocardiograms were collected. The between-subject variability of the magnitude and angles of the tridimensional P, QRS and T modal vectors obtained by use of each lead system was compared. Reproducibility of vectrocardiographic measurements was analyzed by comparing results obtained in 10 calves within a one day interval. The Holmes semi-orthogonal lead system, giving the lowest between subject variability and the highest between-day reproducibility, appeared to be the most reliable lead system in order to apply vectocardiography in the bovine species. PMID- 1414091 TI - Ectopic mammary tissue in the vulva of goats. AB - Ectopic mammary tissue was described in ten goats belonging to the Nubian and Syrian breeds. This consisted of multiple cavitations containing white milky fluid, which greatly resembled milk in colour, odour and composition. Histologically, the tissue was composed of alveoli lined by cuboidal epithelium and contained pinkish staining secretion. Surgical removal of the tissue was achieved without complications. PMID- 1414092 TI - Immunocytochemical identification of a bovine peritoneal mesothelioma. AB - Peritoneal mesotheliomas are uncommon among cows although there has been an increase in the frequency of diagnosis of this neoplasia in the past few years. The case of a 2 year old cow is described. On post-mortem examination, several nodules of variable size were found in the peritoneal cavity. These nodules fused together, but they did not go deep into the organs. Histologically, such nodules were formed by a population of fusiform cells of malignant morphological character and sarcomatous appearance. Immunocytochemical study, using P.A.P. techniques, showed a highly positive reaction towards vimentin and a negative reaction towards wide-spectrum cytokeratins, hence suggesting a mesenchymal origin of the neoplasia. According to the histopathological study, a multifocal peritoneal mesothelioma of sarcomatous appearance was identified. PMID- 1414093 TI - Distribution of ASFV antigens in pig tissues experimentally infected with two different Spanish virus isolates. AB - Lymph nodes, spleen, liver, lung and kidney obtained from pigs experimentally infected with two African Swine Fever Virus (ASFV) isolates of differing virulence were fixed by perfusion with glutaraldehyde and embedded in paraffin. An immunoperoxidase technique using a polyclonal anti-ASFV serum was performed on tissue sections in order to detect ASFV antigen. The distribution of ASFV antigen in such infected organs is shown and the differences between both infections compared and discussed. Monocytes, macrophages, hepatocytes, endothelial cells, neutrophils and epithelial cells were found to contain ASFV antigens. PMID- 1414094 TI - An outbreak of enterotoxaemia in cats. AB - Eighteen local breed cats suffered from enterotoxaemia after scavenging on chicken-remnants. They suffered from vomitus and diarrhoea and collapsed dead after a few hours. An untypable strain of Clostridium perfringens was isolated in pure form and was suspected to be the cause of the outbreak. PMID- 1414095 TI - [The diagnosis of Listeria encephalitis in ruminants using cultural and immunohistological techniques. I. Comparison of different selective media and culture techniques for the detection of Listeria from ruminant brains]. AB - The selective L-PALCAMY differential enrichment broth, the Listeria enrichment broth of the International Dairy Federation, Oxford Listeria selective agar, and PALCAM Listeria selective agar were comparatively examined in the cultural isolation of Listeria spp. from ten ruminant brains. The L-PALCAMY medium proved to be superior to the IDF broth in both selectivity and productivity for Listeria spp. in the brain samples, which were also contaminated with other bacteria. The Oxford and PALCAM agars corresponded in their productivity for Listeria spp. The latter, however, was more selective than the Oxford agar. Bacterial counts of up to 1.2 x 10(9) CFU/g of brain stem sample were made from Listeria monocytogenes (L.m.), and up to 6.2 x 10(4) CFU/g from Listeria innocua. A total of 164 brains from ruminants showing CNS disturbances and/or pathoanatomical CNS alterations were examined using L-PALCAMY medium, and Oxford and PALCAM agar. L.m. could be isolated from 29 of the brains, and Listeria innocua from five. Cultural isolation of both Listeria spp. occurred in one brain. Of 27 brains containing L.m., which were also examined using cold enrichment, L.m. was isolated in 59.3% of the cases with direct culture, in 81.5% of the cases using selective warm enrichment, and in 77.8% of the cases by means of selective cold enrichment. Five cases each were identified solely by cold or warm enrichment, respectively. In investigations of further 69 ruminant brains the number of brains shown to contain L.m. could be increased from seven to 13 by means of selective cold enrichment for three months. PMID- 1414096 TI - Detection of Mycobacterium paratuberculosis antigen with colloidal immunogold in naturally infected sheep. AB - The anti-Mycobacterium paratuberculosis polyclonal serum is proved useful for labelling Mycobacterium paratuberculosis in glutaraldehyde-osmium-fixed and epon embedded intestinal samples from sheep with clinical symptoms of paratuberculosis. M. paratuberculosis marked with antibody-coated colloidal gold stain was seen in macrophages, epithelioid cells, giant cells and neutrophils throughout intestinal mucosa. In large macrophages with a low lysosomal content, a great number of intact mycobacteria was seen within phagosomes. In macrophages with average lysosomal content, very few intact mycobacteria or mycobacterial debris were present and lysosome-phagosome fusions were observed. Mycobacteria within neutrophils were scanty. These results show the usefulness of colloidal immunogold techniques for studies of the pathogenesis of paratuberculosis. PMID- 1414097 TI - Immuno-gold labelling of turkey rhinotracheitis virus. AB - The morphology and morphogenesis of five viruses isolated in Great Britain, France and South Africa from turkeys with rhinotracheitis were examined. The five isolates were antigenically related by immunofluorescence and were indistinguishable by negative contrast and thin section electron microscopy. Negative contrast electron microscopy of infected Vero cell cultures revealed ortho- or paramyxovirus-like particles and helical nucleocapsids 14 nm in diameter with a pitch of 6 nm. The viral nature of these structures was confirmed by immuno-gold labelling, using a hyperimmune rabbit antiserum to TRT virus and 15 nm gold-labelled goat anti-rabbit IgG. Ultrastructural changes characteristics of paramyxovirus infection were observed in Vero cell cultures infected with each of the five TRT virus isolates. These alterations, which included areas of localised thickening of plasma membrane, associated cytoplasmic inclusions of nucleocapsids and budding virus particles also labelled specifically following immunogold staining. These observations are in accord with the suggestion that TRT virus is an avian pneumovirus. PMID- 1414098 TI - [The fatty acid composition of the total lipids in Vibrio cholerae]. AB - The fatty acid composition of total cell lipids of V. albensis typing strains, serovars 01-012, isolated from patients and environmental objects, as well as V. eltor and NAG vibrios, has been studied. Fatty acids contain 14-18 carbon atoms and are mainly represented by unsaturated monoacids. Palmitoleic and oleic acids constitute the greater part of unsaturated acids (their total content is 55.2 71.0%). The level of saturated fatty acids in considerably lower (27.0-43.1%), and these acids are mainly represented by palmitic acid, its maximum level being 28.4%. The similarity of the fatty acid profiles of the lipids common to the strains under study may indicate that these strains are phylogenetically related. PMID- 1414099 TI - [The pathogenicity factors of bacteria in the genus Acinetobacter]. AB - Eighty Acinetobacter strains, isolated in Togliatti from patients with purulent inflammatory diseases, were studied to determine their pathogenicity factors. Out of these 80 strains, 32.5% were found to have enterotoxigenic activity and 46.2%, adhesive activity. They were related to adhesins of the human type and to adhesins of the sheep, rabbit, swine and guinea pig types. But the most important phenomenon established in this study was the combination of different pathogenicity factors detected in Acinetobacter bacteria. Analysis of the combination of pathogenicity factors revealed that 7.5% of Acinetobacter strains had adhesive and enterotoxigenic activity, 15.3% of these strains combined adhesive and hemolytic activity and 1.2% of them were found to be enterotoxigenic and hemolytic. Only 5.0% of Acinetobacter strains were found to carry all there pathogenicity factors simultaneously. PMID- 1414100 TI - [The temperature-induced early and late development of resistance to the bactericidal action of blood serum in Yersinia pseudotuberculosis]. AB - Y. pseudotuberculosis strains were grown at 6 degrees-8 degrees C and then incubated at 37 degrees C. 3-6 hours later serum resistance appeared in the strains having plasmid virulence and producing outer membrane polypeptide with a molecular weight of 120 kD, known as P1. 10-12 hours later serum resistance appeared in the strain having the virulence plasmid, but not producing P1, as well as in strains in which the plasmid was eliminated. PMID- 1414101 TI - [Hospital infections: the problems and ways to resolve them]. AB - The authors present the critical analysis of the existing situation in the spread of purulent septic infections in surgical hospitals of the USSR and the state of epidemiological surveillance. Considering this situation to be highly unfavorable, the authors propose a number of urgent organizational measures (the inclusion of hospital epidemiologists into the medical staff of large clinics, the system of training in this problem). The article deals with the specific features of the epidemiological process in purulent septic infections and the main principles of the organization of the epidemiological surveillance system for this group of infections. PMID- 1414103 TI - [Improvement in the laboratory methods of assessing the safety of the of the pertussis component of DPT vaccine adsorbed]. AB - The mouse paw edema test and the tests for the determination of leukocytosis stimulating and histamine-sensitizing activity are reproducible if standard samples are used and the properties under test are evaluated with reference to the characteristics of standard samples. The standard character of the weight gain test on mice is also enhanced if all conditions of the test are standardized. The most accurate information on the toxicity of the pertussis component of adsorbed DPT vaccine can be obtained if a single human dose (0.5 ml) is injected to mice and the toxicity of the vaccine is estimated from the weight gain registered in the test mice and the control animals. The use of standard samples in each test makes it possible to observe the conditions for controlling the toxicity of the tested preparations. PMID- 1414102 TI - [The protective activity of preparations made from the tick-borne encephalitis virus grown using different cell cultures]. AB - The preparations of tick-borne encephalitis (TBE) virus grown in swine embryo kidney cell culture have been shown to possess pronounced protective activity per unit of virion protein E in comparison with TBE virus preparations derived from cell culture 4647 and chick embryo cell culture. The antigenic activity of all virus preparations under study has proved to be practically the same. The role of post-translation modifications of TBE virus protein E in the manifestation of some of its biological properties is discussed. PMID- 1414104 TI - [The antibacterial immunity of people under dynamic observation in an altered radiation situation]. AB - The comparative study of the isolation rate, level, antigenic and class specificity of serum antibodies to the causative agents of purulent septic infections (Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis) and acute enteric infections in healthy adults with different ABO blood groups before (836 persons) and after (1,429 persons) the catastrophe at the Chernobyl nuclear power station was made. The study revealed the fact that the genesis of antibodies directed against different microorganisms can be stimulated without additional antigenic challenge in the form of disease or immunization, which was definitely indicative of the influence of small radiation doses in Kiev on the humoral immunity of the population. The multifactor character of the dependence of antibacterial antibody formation under altered radiation conditions on the specific features of the infective agent and the intensity of its circulation among the population, individual immune responsiveness of the body and concrete radiation conditions was established. PMID- 1414105 TI - [A comparative study of the expediency of using different chemical methods for determining protein in allergen preparations]. AB - Parallel use of some known chemical procedures for measurements of protein in commercial forms of allergens revealed considerable variations in the results, which was due to the nature of the methods used and to admixtures of different substances in the preparations under study. The conclusion on the necessity of using at least two methods of protein determination for the standardization of allergens was made. Preference was given to Bradford's method. As the standardization of allergens manufactured in the USSR is carried out on the basis of the quantitative determination of protein (in PNU), this problem is of not only theoretical, but also practical importance. PMID- 1414106 TI - [The syndromal approach to the diagnosis of toxic food poisonings]. AB - The authors criticize the nosological principle of the diagnosis of toxic infections and believe that in a vast majority of cases such diagnosis must be based on syndromes. The only exceptions are cases of mass outbreaks and hospital infections. The definition of alimentary toxic infection is given, the difficulties of their clinical diagnosis and the ways to overcome these difficulties are indicated. PMID- 1414107 TI - [Yersinia pestis adenylate cyclase and the deregulation of transmembrane signal transmission in the peritoneal leukocytes of white mice]. PMID- 1414108 TI - [New developments in the classification and identification of enterobacteria]. PMID- 1414109 TI - [The adhesive properties of S and R mutants of Salmonella minnesota during batch cultivation]. AB - The study of the adhesive, surface-electrical and hydrophobic properties of S. minnesota S- and R-mutants in the process batch cultivation has revealed that the maximum values of the above parameters are characteristic of the stationary phase of culture growth and their minimum values, of the end of the lag phase. Electrophoretic mobility and adhesiveness increase from S- to Re-chemotype. The surface of Salmonella S-form is more hydrophilic, than in R-mutants which are indistinguishable in the degree of their hydrophobic properties. The heterogeneity of the populations under study with respect to the electrophoretic mobility and adhesiveness of cells has been detected. PMID- 1414110 TI - [The random parasitism of microorganisms]. PMID- 1414111 TI - [The phenotype of the causative agent of yersiniosis and its significance for diagnosis]. PMID- 1414112 TI - [The advantages and prospects of using immunoenzyme analysis for assessing pertussis immunity]. PMID- 1414113 TI - [The individualized procedure for immunoprophylaxis]. PMID- 1414114 TI - [Basic directions in the development of individual student capacities and of teacher creative activity in a department of microbiology]. PMID- 1414115 TI - [People's Commissar of Public Health G. N. Kaminskii (1895-1938) and medical science]. PMID- 1414116 TI - [Sterol transformation by Escherichia]. AB - The use of the Liebermann-Burhard reaction and the thin-layer chromatography of nonsaponifiable lipids of culture medium (donor blood serum) permitted the isolation of three biological variants of Escherichia in the process of their 48 hour cultivation in this medium. The cholesterol-destroying variant of Escherichia is characterized by a decrease in the content of total, free, esterified cholesterol and a decrease in the occurrence of fractions corresponding to cholesterol, delta 4-cholestenone-3, delta 5-cholestenone-3), as well as nonsaponifiable lipid, where Rf was equal to 0.36; two fractions of labeled nonsaponifiable lipids, not corresponding to cholesterol, appeared on plasma with sodium acetate-1-14C. Cholesterol-transforming biovars produced insignificant changes in the content of chemically determined cholesterol in the medium, but in plasma nonsaponifiable lipid with Rf = 0.26 and other less polar lipids were found. Escherichia strains increasing the amount of chemically determined cholesterol in the process of their growth more frequently transformed or used nonsaponifiable lipids with Rf = 0.26 and 0.42. As a rule, the occurrence of cholesterol and less polar lipids increased. The sodium acetate-1-14C was incorporated into 3-4 fractions of nonsaponifiable lipids, one of them being identified as cholesterol. PMID- 1414117 TI - Distribution of cortical neurons projecting to dorsal column nuclear complex and spinal cord in the hedgehog tenrec, Echinops telfairi. AB - Using retrograde axonal flow and wheatgerm agglutinin conjugated to horseradish peroxidase, we studied the distribution of cortical neurons giving rise to spinal and dorsal column nuclear projections, and correlated the regions involved in the projections with the cytoarchitectonic areas recently identified in the lesser hedgehog tenrec, Echinops telfairi (Insectivora). Labeled cortical neurons were most numerous following injections of tracer into higher cervical segments, whereas almost none were found following thoracic injections. The cortical labeling appeared more prominent ipsilaterally than contralaterally after spinal injections, although it was more prominent on the contralateral side after injection into the dorsal column nuclear complex. The majority of labeled neurons found in lamina V occupied the neocortex adjacent to the interhemispheric fissure along the rostrocaudal extent of the small corpus callosum. This location corresponded to an intermediate rostrocaudal portion of the hemisphere, and particularly to area 2 of Rehkamper. In some cases, adjacent portions of areas 1 and 3 were also involved, as well as neocortical regions of the lateral hemisphere. The present data did not suggest a somatotopic organization of the projections; likewise, evidence for the presence of more than one somatosensorimotor representation was sparse. PMID- 1414118 TI - The ganglionic origins and central projections of primary sensory neurons innervating the upper and lower lips in the rat. AB - Retrograde and transganglionic transport of horseradish peroxidase (HRP) was used to investigate the neurons innervating the upper and the lower lips and their central projections in the rat. Both the upper and the lower lips were observed to be innervated by a very large number of trigeminal sensory neurons, with their cell bodies located in the maxillary and the mandibular parts of the trigeminal ganglion, respectively. The central projections of neurons innervating the upper lip formed a long continuous column starting rostrally at midlevels of the trigeminal main sensory nucleus (5P) and extending caudally through the C1 dorsal horn, with occasional fibers reaching the C3 segment. The heaviest projections appeared in the middle portions of 5P and nucleus interpolaris (5I), as well as in the rostral part of nucleus caudalis (5C). A small but consistent projection to the solitary tract nucleus, originating from cells in the inferior vagal ganglion, was observed in the upper-lip experiments. The central projections from neurons innervating the lower lip also appeared as a long column located dorsally or dorsomedially to the projections from the upper lip. The most prominent projections from the lower lip were located in the caudal part of 5P, the middle part of 5I, and the caudal two-thirds of 5C. Sparse projections could be traced as far caudally as C4. At 5C and cervical levels, some labeling appeared contralaterally in the same location as on the ipsilateral side. PMID- 1414119 TI - Retrograde labeling of lumbosacral interneurons following injections of red and green fluorescent microspheres into hindlimb motor nuclei of the cat. AB - In order to map the laminar and segmental positions of lumbosacral interneurons that project to L7 motor nuclei, red and green fluorescent latex microspheres ("beads") were pressure-injected through micropipettes into the deep peroneal or posterior biceps-semitendinosus motoneuron pools of cats. Micropipette tips were positioned by recording the antidromic field potentials evoked by electrical stimulation of the muscle nerves. Projecting interneurons were identified by the presence of retrogradely transported beads. Small bead injections labeled large numbers of neurons. These were observed in all the spinal segments examined, L1 S2, and were most densely concentrated within laminae VI and VII ipsilateral to the injections and lamina VIII contralaterally. In addition, significant numbers of labeled cells were observed in lateral lamina V ipsilaterally and in lamina X. A few cells with bilateral projections were double-labeled following injections of red and green beads on opposite sides of the cord. These were most often observed in midlumbar segments (L3-L5) in medial regions of the gray matter. The results suggest that the intermediate zone (laminae V-VIII and X) of the lumbosacral spinal cord is a major source of interneuronal projections to the L7 ventral horn. This is true for both lateral and medial areas of the intermediate zone, as the fluorescent microspheres labeled neurons in medial regions of the cord largely undetected in previous studies in which other methodologies were employed. PMID- 1414120 TI - The sensory effects of l-menthol on human skin. AB - Psychophysical measurements were made of the sensory effects of l-menthol applied topically to the forearm under controlled thermal conditions. In the first experiment, subjects judged the intensity and quality of sensations produced by warming or cooling the skin in the presence of menthol or the vehicle. During cooling, menthol intensified cutaneous sensations and increased reports of burning. During warming, menthol intensified sensations transiently at low temperatures and weakened them lastingly at higher temperatures; the frequency of reports of burning varied with intensity. A second experiment tested the hypothesis that menthol would lower the threshold for warmth and raise the threshold for heat pain. No change in either threshold was observed. The primary sensory effects of l-menthol on hairy skin are therefore to heighten the perception of cooling and to attenuate the perception of moderate warming. In contrast with other common chemical irritants, menthol's pungent qualities appear to be enhanced by cooling and suppressed by warming; this suggests that its sensory irritancy may be attributable to the stimulation of a population of high threshold cold fibers or cold-sensitive nociceptors. PMID- 1414121 TI - Further evidence for the involvement of SmI cortical neurons in nociception: modifications of their responsiveness over the early stage of a carrageenin induced inflammation in the rat. AB - In this electrophysiological study, changes in the responsiveness of neurons in the primary somatosensory (SmI) cortex in rats were analyzed during the development of carrageenin (CRG)-induced inflammation, an animal model of acute inflammatory hyperalgesia. SmI neurons were characterized as responding to non noxious light touch, non-noxious articular movement, or noxious pinch. A total of 23 neurons so characterized in three groups were recorded for 60 min (17 of these neurons were recorded for up to 150 min) after an intraplantar injection of CRG. The possible modifications in their background and evoked activities were analyzed over this period of time. After CRG administration, cells responding to noxious pinch stimuli (n = 8) showed a nonsignificant increase in spontaneous activity, but a significant increase in their evoked response to pinch. These results were quite similar to past observations in the ventrobasal nucleus of the thalamus (VB). Cells responding to non-noxious articular stimulation (n = 6) showed variable modifications and no significant increase in the mean evoked response for up to 60 min. These results for articular cells were also quite comparable to results seen for VB responses for similar cells. However, mean spontaneous activity, which showed a highly variable increase, was significantly increased after 60 min. The depressive effect of a local anesthetic, Xylocaine, was tested on the activities of four cells (one pinch, three light touch units) 60 min after CRG administration over a 20-min interval. Xylocaine was found to depress both spontaneous activity and responses to the effective somatic stimulus, thereby implying that the observed central modifications in neuronal discharge are linked to the peripheral inflammation. Modifications observed for each group of cells are compared with past observations in peripheral fibers, in spinal dorsal horn neurons, and especially in the VB under similar inflammatory conditions. These data confirm that the SmI cortex is involved in the nociceptive process. Furthermore, the contrast between some modifications observed at this level and past observations under similar inflammatory conditions suggests a unique role of some cortical neurons, which might partially account for mechanical allodynia. PMID- 1414122 TI - [The expression of TGF beta-related mRNAs in the early development of Xenopus]. AB - Using porcine TGF beta 1-cDNA probe, we found that three TGF beta-related mRNAs (4.2 kb, 3.2 kb and 2.3 kb) were detected in blastula (Stg. 7/8). The 4.2 kb and 3.2 kb mRNAs were very highly expressed in the blastula (Fig. 3). However, we could hardly detect them in embryos of cleavage, gestrula and neurula stages. On the other hand, the 2.3 kb mRNA could be identified in embryos of cleavage stages, blastula, gastrula and neurula and the quantity was rather stable. Comparing the quantities of TGF beta-related mRNAs in different parts of blastula, that is, animal half or vegetal half and dorsal or ventral half, we found that the transcripts were enriched in the vegetal hemisphere (Fig. 6). But no obvious difference between dorsal and ventral halves could be detected (Fig. 7). PMID- 1414123 TI - [Immunohistochemical studies on the TGF beta-related protein in the early development of Xenopus laevis]. AB - By the method of immunocytochemistry, using the polyclonal antibodies raised against the 1-29 N-terminal residues of TGF beta-1, we found that the protein could bind to the antibodies was present in the early embryos of Xenopus. The protein was named TGF beta-related protein. It was distributed mainly in the endoderm from blastula (stg. 7) to late neurula. In the blastula (stg. 8), the protein was localized in the vegetal hemisphere near the floor of the blastocoel [Plate I, Fig. 1]. In the early gastrula (stg. 10.5) [Plate I, Fig. 2], it was localized in the central part of the vegetal hemisphere. In late gastrula (stg. 12), it was mainly distributed around the gastrocoel [Plate I, Fig. 3], but the fluorescence in endoderm cells (ventral part beneath the gastrocoel) was stronger than in the mesoderm cells (dorsal part of the gastrocoel). In the early neurula (stg. 14), the whole endoderm displayed strong fluorescence and the part of dorsal mesoderm (presumptive somite & notochord) close to endoderm was also found to be positively stained [Plate I, Fig. 4,5], but the part close to neural plate was negative. In The late neurula (stg. 20) [Plate I, Fig. 6], it was found in the central area of yolk mass (endoderm cells). No positive stain was detected in the unfertilized egg, embryos earlier than stage and later than stage 20/21.2+ protein in early development. PMID- 1414124 TI - [The effect of microinjection of anti-TGF beta-1 antibodies on the early development of Xenopus laevis]. AB - In order to testify the function of the TGF beta related protein, we microinjected the antibodies against the TGF beta-1 to one blastomere of two-cell stage embryos. Dosages of antibodies injected were 24-36 ng, 12 -18 ng, 6-9 ng and 1.5-2.25 ng. Malformed embryos with exposed yolk mass were produced. They were designated as YE-1, YE-2 and YE-3 according to the degree of malformation which was found to be related to the dosage of antibodies injected to the blastomere. These malformed embryos could normally develop to blastula, but the yolk mass was exposed on the injection half during gastrulation. In the group with the highest dosage, the most seriously affected embryos belong to the YE-1. For most of them, no muscle tissue could be found from head to tail in the injection half, the development of mesoderm seemed to be thoroughly inhibited. YE 2 was the group with decreased dosage, small block of muscle tissue was usually observed in the injection half. YE-3 was the least affected group with the injection half containing blocks of muscle tissue similar to that of the non injection half. The different groups of malformations seemed to be related to the degree and range of interference on gastrulation. In the group with highest dosage, the gastrulation of the entire injection half seemed to be prohibited, and YE-1 was produced. In the groups with lower dosages, only part of injection half was interfered, and YE-3 v and YE-3 d were resulted. From the results mentioned above, we concluded that TGF beta-related protein are not only present in the early embryos of Xenopus laevis, but also may be concerned with mesoderm induction. PMID- 1414125 TI - [A comparative study on the metabolism of nucleic acids during the subculture and differentiation of tobacco callus]. AB - Changes in the contents of DNA and RNA, RNA species, the synthesis rates of DNA and RNA, and the activity of DNase and RNase were investigated in the callus of tobacco (Nicotiana tabacum L. cv. Willow Leaf) during subculture and differentiation. The contents of DNA and RNA were higher in differentiating callus than that in subcultured callus. After day 12, the contents of DNA and RNA in differentiating callus rose continuously while the contents of DNA and RNA in subcultured callus remained constant. Changes in RNA species and its relationship to total RNA level were also analyzed. At the stage of shoot primordium formation in differentiating callus, the activity of RNase increased markedly and the synthesis rate of RNA increased continuously; while the RNase activity and the synthesis rate of RNA in subcultured callus were much lower during the same period. During the period of shoot growth, the synthesis rate of DNA in differentiating callus was elevated compared to that in subcultured callus. The results above suggested that the metabolism of nucleic acids in differentiating callus was more active than that in subcultured callus. PMID- 1414126 TI - [Studies on genetic engineering of human insulin-purification and characterization of human proinsulin and insulin]. AB - E. coli DH 5 alpha cells harboring a plasmid pWR 590-BCA 4 for fused human proinsulin production were cultured. The fused human proinsulin was isolated from the fermented cells and then subjected it to cleavage with BrCN. The cleaved product was then converted to crude proinsulin-S-sulfonate using oxidative sulfitolysis. The isolation of human proinsulin-S-sulfonate was accomplished by ion exchange chromatography on QAE-sephadex A-25, followed by gel filtration on sephadex G-50. The purified human proinsulin-S-sulfonate was folded using a disulfide interchange method. The folding mixture was then chromatographed on sephadex G-50 and purified proinsulin was obtained. The proinsulin was then converted to human insulin and C-peptide by a combination cleavage with trypsin and carboxypeptidase B. The total yield of human insulin was about 5 mg/L The Zinc insulin crystals were obtained with amorphous human insulin using citrate method. The amino acid composition N-terminal sequences as well as C-terminal amino acid residues are in agreement with expected results. The hypoglycemic activity of purified human insulin is 26-27 U/mg, as judged by mouse convulsion assay, and the RIA activity is about 99% of that of porcine insulin. PMID- 1414127 TI - Molecular and functional properties of EF-Tu from Calderobacterium hydrogenophilum. AB - Protein synthesis elongation factor Tu (EF-Tu) was purified from an extreme thermophilic hydrogen-oxidizing bacterium Calderobacterium hydrogenophilum. The relative molecular mass of EF-Tu. GDP was 51,000. The factor was heat stable and lost only 50% of its activity after heating at 80 degrees C for 5 min. Native and reduced EF-Tu or EF-Tu. GDP contained one SH-reactive group. The elongation factors from C. hydrogenophilum and E. coli were shown to be immunologically identical. From the Southern hybridization analysis seems to suggest that chromosome DNA of C. hydrogenophilum has two tuf genes. PMID- 1414128 TI - [Association of chromosomal telomere DNA with nuclear matrix in HeLa cells]. AB - Nuclear matrix from HeLa cells was gently extracted with a high salt solution and treated with DNase I. DNA that remained associated with the nuclear matrix (N. M. DNA) and DNA fragments released into the supernatant (SN.DNA) were isolated respectively and dot hybridized to human telomere sequence (AGGGTT/TCCCAA)40 probe. As the time of DNase I treatment was extended, the amount of N. M. DNA decreased while the concentration of telomere sequence in N.M. DNA proportionally increased. These preliminary results suggest that the telomere sequence is tightly bound to nuclear matrix in HeLa cells. PMID- 1414129 TI - [The dynamics of two types of tyrosine protein kinases in the proliferation of cultivated vascular smooth muscle cells]. AB - We have studied the membrane-bound tyrosine protein kinases (TPK) in cultivated aortic smooth muscle cells (ASMC) from the rabbit, and found that the cytosolic (membranous)TPK and the nuclear (membranous)TPK are two distinctive types of isozymes as judged by criteria on dynamics: (1) using synthetic poly(Glu. Ala. Tyr)n(6:3:1) as a substrate, the relative extents of stimulation by Mn2+ (450%) was more effective than that by Mg2+ (100%) on cytosolic TPK, but Mn2+ was less effective (100%) than Mg2+ (130%) on nuclear TPK: (2) the concentrations of Mn2+ and Mg2+ giving maximal stimulation on cytosolic TPK were 15 mmol/L and 50 mmol/L, whereas on nuclear TPK were 1 mmol/L and 5 mmol/L, respectively. These results indicate that the attitudes toward Mn2+ and Mg2+ can distinguish the cytosolic TPK from the nuclear one. In nucleus, with the entry of ASMC from G0 to G1 stage, TPK activity increased rapidly and reached the peak (12 times G0 activity) at the early G1 stage (3 hrs from G0), then decreased dramatically to basic line, and remained at a lower level thereafter. In cytosol, the TPK activity decreased with the entry of ASMC from G0 to G1 stage and reached its lowest point at the middle of G1 stage (6 hrs from G0), and then increased with a transient peak at the late G1 stage (9 hrs). It went down to G0 level before DNA synthesis. PMID- 1414130 TI - [Occupational transmission by HIV and by hepatitis B virus. Attitude of Belgian surgeons and anesthetists. An opinion survey]. AB - Risk of professional transmission of hepatitis B is known since the seventies. Recently the possibility of HIV transmission during surgical practice was demonstrated. It was interesting to assess Belgian surgeons and anesthetists opinion about this risk and about the precautions taken. An opinion survey was performed with a representative sample of Belgian surgeons and orthopedists (340) as well as anesthetists (100). Risks of transmission of HIV and possible elementary precautions are not well known. The rate of vaccination against hepatitis B is low, specially in smaller hospitals. However the frequency of injuries during practice is high in surgeons as well as in anesthetists. This study shows that important information efforts about the risks of HIV infection and the possible precautions to be taken are still necessary. Information about the need for vaccination against hepatitis B should also be done, considering the high incidence of operative injuries. PMID- 1414131 TI - [Primary inguinal hernia: Lichtenstein's ambulatory hernioplasty: early clinical results and economic implications. Study of the initial 130 surgical cases]. AB - The authors report their preliminary experience of 130 ambulatory treatment under local anesthesia of primary inguinal hernia. This method of treatment is very well accepted by the patients. There are few early recurrences. This method of treatment is very cost-effective. PMID- 1414132 TI - [Delayed perforation of the sigmoid colon following closed abdominal trauma. Apropos of a case report]. AB - Blunt abdominal trauma and delayed colon perforations are not common and usually occur in patients sustaining other injuries, but also as isolated event. We report a case of delayed perforation of sigmoid colon, three days after a blunt abdominal trauma in a male adult. It was caused by disinsertion of sigmoid colon mesentery for about ten centimeters. This condition is discussed with literature review. PMID- 1414134 TI - [Malignant retroperitoneal paraganglioma. Case report and literature review]. AB - The authors report a case with a retroperitoneal recurrent malignant non secretory neuroendocrine tumor. The diagnosis of this rare pathology is based on immunohistochemical and electron microscopic techniques. Due to radio- and chemotherapeutic resistance of the tumor, the therapy has to be surgical. The locoregional recurrent nature of the disease asks for a close clinical and radiological follow-up. PMID- 1414133 TI - [Small intestinal ulceration and stenosis induced by non-steroidal anti inflammatory agents]. AB - We report a case who developed a small bowel ulceration in a long segment of distal duodenum and proximal jejunum, a few days after he had taken high doses of diclofenac. After a month, it was complicated by a stenosis of the same segment. Nonsteroidal antiinflammatory drugs have recently been recognised as a possible etiologic factor of small bowel ulcerations. Clinical findings are aspecific. Complications of small bowel ulcerations are: obstruction, perforation or bleeding. Those have to be treated by surgery. We proposed a physiopathologic model and correlated it with histological findings. CONCLUSION: careful prescription of those drugs has to be pursued and one should think about a small bowel ulceration in a patient with an abdominal syndrome, who takes non-steroidal antiinflammatory drugs. PMID- 1414135 TI - Massive intestinal haemorrhage due to a solitary jejunal metastasis of a primary bronchogenic tumour. AB - A case is presented of a 72-year old male patient presenting with a massive intestinal blood loss due to a solitary jejunal metastasis of a poorly differentiated adenocarcinoma of the right lung resected two years earlier. After diagnostic workup and stabilization a small bowel resection with end to end anastomosis was performed. Patient is alive and well 5 months after operation. Solitary bleeding intestinal metastasis of a primary bronchogenic tumour are extremely rare but should be included in the differential diagnosis of gastrointestinal blood loss in a patient with a known bronchogenic tumour. Resection with end to end anastomosis is the treatment of choice. PMID- 1414136 TI - Simulation of appendicitis by tumor-like lesion of cecum. AB - Four cases are presented in which an initial diagnosis of appendicitis was made. At laparotomy, a cecal lesion simulating a tumour was found. Pathological examination showed inflammatory granulomatous tumour against foreign body, non specific ulcer, diverticulitis and acute solitary diverticulitis. When malignancy is excluded, hemicolectomy is not necessarily the best treatment and we propose conservative management for these patients. PMID- 1414138 TI - Traumatic false aneurysm of the superficial temporal artery. AB - Traumatic false aneurysms of the superficial temporal artery are very infrequent. They usually do not reveal themselves clinically until 1 to 6 weeks after the initial trauma. Diagnostic techniques are echo-doppler, CT-scan and arteriography; treatment is surgical. PMID- 1414137 TI - [Neonatal ovarian cyst. Case report and literature review]. AB - The authors report a case of antenatal ultrasound diagnosis of a large fetal ovarian cyst; surgical extirpation in the neonatal period due to locoregional complications. Review of the literature; diagnosis, treatment, complications. PMID- 1414139 TI - Late results in replanted digits. Is replantation of a single digit worthwhile? AB - During the period 1980-1989 35 patients with successfully replanted digits could be selected. Only 17 patients with 32 long fingers and 2 thumbs replanted were prepared to cooperate for this retrospective study, looking for the late functional results. Mobility of the replanted digits was measured by the TAM value. Power was indicated by grip strength and tip pinch. Weber two-point discrimination test and Von Frey test were used to investigate sensibility. Most patients show cold-intolerance. Mobility was worse for the more proximal replantations. Replantations distal to PIP do functionally very well. Therefore single digit amputations should be considered as an indication for replantation, especially amputations distal to the pip. Ring and little finger replantations have a better mobility than index and middle fingers. Mobility in younger patients is also better. Grip strength and tip pinch are respectively 66% and 73% of the normal values. All patients (except 2) could return to their work in a reasonably short time (average 5 months). PMID- 1414140 TI - Degloving injuries. A retrospective study at the University Hospital Rotterdam. AB - Degloving injuries are severe and frequently underestimated lesions. In a retrospective study, 65 patients treated between 1985 and 1991 were reviewed. Therapy consisted of surgical exploration as soon after injury as possible, with defatting of the avulsed skin and its replacement on the most functionally important sites. The remaining raw areas were covered with split skin grafts (SSG). This technique reduced morbidity, hospital stay and work incapacity, as compared with patients treated by other methods. PMID- 1414141 TI - [The treatment of giant lipomas]. AB - Lipomas are the most frequent benign tumours. Usually they are removed for cosmetic reasons only. For the treatment of giant lipomas, liposuction was proposed to reduce the size of the skin incision. The reliability of this technique was compared to surgical resection in a series of 30 patients presenting with a giant lipoma. One year follow-up of these patients showed a high percentage of recurrences after liposuction but only one after excision. PMID- 1414142 TI - Corticotropin-releasing hormone in health and disease: an update. AB - Corticotropin-releasing hormone (CRH) was initially sequenced and identified in 1981, and has since become established as the principal organizer of the stress response. It causes activation of the pituitary-adrenal axis, behavioural arousal, sympathetic stimulation and a decrease in appetite. In vitro studies have shown regulation of hypothalamic CRH by a variety of neuro-transmitters, including the cytokines interleukin-1 and interleukin-6. However, circulating CRH is mainly derived from extra-hypothalamic sites, and levels may be elevated in patients with tumours secreting ectopic CRH. The placenta is a further source of CRH, which may be specifically raised in patients with pre-eclampsia, and could be a factor in the initiation of parturition. The recently identified CRH binding protein may play a vital role in this process. Clinically, CRH testing has become extremely useful in the diagnosis and differential diagnosis of Cushing's syndrome, and particularly for the localization of ACTH following inferior petrosal sinus catheterization. There is considerable evidence that many patients with depressive illness may have a disturbance of the central control of CRH, and this may be become of increasing importance in the therapy of this common condition. There are also intriguing new data suggesting that abnormalities in CRH regulation may be involved in the pathogenesis of inflammatory arthritis. PMID- 1414143 TI - Effects of corticotropin-releasing hormone on the postoperative course of elderly patients under long-term artificial respiration. AB - In both human and animal studies a stimulatory effect of corticotropin-releasing hormone (CRH) on respiration and on cognitive parameters has been demonstrated. Our own studies employing human CRH (hCRH) iv in healthy volunteers and different groups of patients have shown hCRH to be a safe drug. We prospectively studied the clinical effects of a standardized dose of 100 micrograms hCRH iv in 12 elderly patients following major abdominal surgery who remained comatose and were under prolonged respirator therapy over a mean period of 37 days. Cardio respiratory parameters, blood gas values, plasma cortisol and catecholamines were evaluated before and 30 min following hCRH injection. Furthermore, vigilance was tested using a score system. Ventilation was markedly enhanced following hCRH injection while the cardiovascular parameters were only moderately affected. Vigilance was augmented in all subjects and improved impressively in five patients. The changes were of great benefit for the patients treated and supported their respirator weaning procedures and mobilization training. PMID- 1414144 TI - The effect of a met-enkephalin analogue on growth hormone, prolactin, gonadotropins, cortisol and thyroid stimulating hormone in healthy elderly men. AB - The aim of the study was to evaluate the effect of the guanyl derivative of the opioid analogue D-ala2,MePhe4-Met-enkephalin-(o)-ol (G-DAMME) on pituitary secretion in healthy elderly men. Nine healthy elderly men (65-88 years) and 10 young adults (20-30 years) were studied. GH, PRL, gonadotropins, cortisol (to evaluate the effect on ACTH) and TSH were measured after G-DAMME (0.25 mg iv) or placebo administration. In elderly men, the GH response to G-DAMME was reduced or absent, while prompt GH release was found in all young men. G-DAMME lowered LH levels in young men but not in elderly men. No significant variations in FSH levels after G-DAMME and placebo were noted in either group of subjects. A similar and significant rise in PRL and TSH, and a fall in cortisol, after G DAMME was observed in both elderly and young adults. We have demonstrated that the sensitivity to opioid modulation by G-DAMME on PRL, TSH and cortisol secretion is unchanged with aging. On the other hand, the data indicate that LH and GH responsiveness to G-DAMME change with age. PMID- 1414145 TI - Effect of digoxin on the in vitro secretion of renin and angiotensin II/III immunoreactivity by the human adrenal gland. AB - Cardiac glycosides in man inhibit renin secretion, probably through a direct effect at the renal level (i.e. inhibition of juxtaglomerular cell Na/K ATPase). Since there is evidence that the human adrenal possesses an intrinsic renin angiotensin system, we investigated the effect of digoxin on the in vitro generation of renin and angiotensin II/III, as well as of aldosterone, by the human adrenal gland. Minced normal adrenal tissues were studied in a superfusion system, measuring in the 15-min superfusate fractions active renin by immunoradiometric assay and angiotensin II/III and aldosterone by radioimmunoassay, respectively. In a first set of four experiments using different concentrations of digoxin in sequence for 45 min periods, digoxin 10( 5), but not 10(-8) and 10(-6) mol/l, significantly reduced renin and angiotensin II/III output from adrenals, while no change in aldosterone was observed. In a second set of three experiments, the addition of digoxin 10(-5) mol/l for 120 min caused a sustained reduction of renin and angiotensin II/III, but not of aldosterone. In the final experiment, the decrease of renin and angiotensin II/III during superfusion with digoxin 10(-5) mol/l was significantly greater than that observed during superfusion with digoxin in the presence of antidigoxin antibodies. Our data indicate that digoxin at high doses reduces renin and angiotensin II/III but not aldosterone secretion by the human adrenal gland. This suggests two different effects of digoxin, probably both mediated by inhibition of the Na/K ATPase activity, on the adrenal renin-angiotensin- and aldosterone secreting cells. PMID- 1414146 TI - A monthly cycle in the plasma concentration of GnRH and the glomerular filtered load of GnRH during second trimester pregnancy. AB - Six healthy women were examined three times a week during the second trimester. The aim of the study was to test the existence of a monthly cycle in plasma GnRH. Because the kidney plays a dominant part in the elimination of small peptides from the circulation by filtration, the filtered load (P-GnRH x GFR) of GnRH was estimated and tested for a cycle. A mathematical model (parabolas overlaid with a cosine curve and containing parameters for cycle length, cycle amplitude and phase) was used in a multivariate analysis of changes in plasma GnRH, creatinine clearance and GnRH filtered load. We found significant monthly cycles in plasma GnRH (p = 0.003) and in GnRH filtered load (p = 0.004), but no significance for a cycle in creatinine clearance. As an intermediate result we demonstrated that the tubular reabsorption of GnRH was unsaturated for all values of plasma GnRH and GnRH filtered load in question. The increased pregnancy level of plasma GnRH originates in part in the placenta, but we assume that the cycle generator is contained in the maternal neuroendocrine system. PMID- 1414147 TI - Body weight and/or endogenous estradiol as determinants of cortical bone mass and bone loss in healthy early postmenopausal women. AB - The objective was to study the independent relationships of body mass index and endogenous estradiol to cortical bone mineral density and the rate of cortical bone loss at the radius in healthy early postmenopausal women. Fifty-one healthy early postmenopausal women (aged 58-66 years) participated. The women were a subset of a population participating in a 10-year longitudinal study to elucidate the influence of dietary calcium on the rate of cortical bone loss. Cortical bone mineral density at the radius, body weight and body height were measured annually (1979-89). Concentrations of sex steroids were measured in serum samples collected during the last year of follow-up (1989). Endogenous estradiol levels, although significantly positively correlated with body mass index, were not independently related to bone mass indices of the radius. Body mass index, on the other hand, was found to be positively related to cortical bone mineral density and negatively to the rate of bone loss, even after adjustments had been made for confounding factors. Our results suggest that the level of total estradiol is not an important determinant of cortical bone mass indices in healthy early postmenopausal women. Other factors of overweight such as mechanical loading may be important. PMID- 1414148 TI - The hypothalamo-pituitary regulation of androgen secretion in young men after prolonged physical stress combined with energy and sleep deprivation. AB - During a five days' military training course for male cadets with hard physical activity day and night and almost no sleep or food, a decrease was found in LH, FSH, PRL and TSH. A decrease was also found in testosterone, dihydrotestosterone (DHT), androstenedione, dehydroepiandrosterone and 17 alpha-OH progesterone, whereas dehydroepiandrosterone-sulfate increased twofold. The LH and FSH responses to GnRH intravenously were increased at the end of the course. This demonstrates enhanced pituitary reserves of gonadotropin, or, alternatively, increased sensitivity to GnRH stimulation and may be due to decreased hypothalamic secretion of GnRH during the course. The decreased DHT and testosterone levels were almost normalized after HCG stimulation, indicating a gonadotropin regulated decrease in testosterone secretion during the course. In spite of fairly weak correlation between the alteration in gonadotropins and androgens it is concluded that there is a major regulation of testicular androgen secretion during prolonged stress by the hypothalamo-pituitary axis. PMID- 1414149 TI - Acute beta-interferon or thymopentin administration increases plasma growth hormone and cortisol levels in children. AB - The interaction between the immune and endocrine systems has recently been investigated. Hodgkin's disease represents a model of immune disturbance frequently associated with endocrine impairment. The present study evaluated the effect of the acute administration of beta-interferon or thymopentin on plasma growth hormone, prolactin and cortisol levels in children with Hodgkin's disease (N = 8) and age- and sex-matched healthy controls (N = 8). beta-interferon (1,000,000 IU), thymopentin (50 mg) or placebo (saline) were injected after two basal blood samples (-15 and 0) and further samples were drawn at 15, 30, 45, 60, 90 and 120 min. Plasma growth hormone, prolactin and cortisol levels were measured by specific RIAs. Plasma prolactin levels did not show significant change following beta-interferon or thymopentin injection in either the controls or the patients. In the patients with Hodgkin's disease, beta-interferon injection induced a significant increase in both plasma growth hormone and cortisol levels, while thymopentin was not effective. In controls both thymopentin and beta-interferon administration increased plasma growth hormone and cortisol levels. These results indicate that beta-interferon and thymopentin are immune substances active on the release of growth hormone and cortisol in healthy children. The lack of effect of thymopentin in children with Hodgkin's disease suggests an impairment of the immune-endocrine interaction in these patients. PMID- 1414150 TI - Interrelationships between urinary sodium, calcium, hydroxyproline and serum PTH in healthy subjects. AB - The effect of sodium intake on the excretion of calcium, hydroxyproline (OHP) and serum parathyroid hormone (PTH) was examined. When seven healthy males increased their sodium intake by 200 mmol/day, excretion of calcium increased by 1.70 mmol/day and that of OHP by 27%. Serum PTH, however, did not increase significantly. In a cross-sectional study of 334 healthy female subjects there were strong positive correlations between fasting urinary sodium/creatinine (Na/Cr) and calcium/creatinine (Ca/Cr) ratios (r = 0.573) and between Na/Cr and urinary OHP/Cr ratios (r = 0.246). Serum PTH was negatively correlated with Na/Cr ratio (r = -0.161). We conclude that an increase in dietary sodium causes calciuria and an increase in hydroxyproline excretion. The results do not support the hypothesis that this is mediated by PTH. PMID- 1414151 TI - Glucose metabolism in embryos of normal and diabetic rats during organogenesis. AB - To investigate whether malformations in the offspring of diabetic rats are related to a disturbed embryonic glucose metabolism, lactate production, lactate content and glucose oxidation in embryos of normal and manifestly diabetic rats were measured in vitro during the period of organogenesis. The embryonic production and content of lactate decreased by 90% between gestational days 10 and 11. On both gestational days the embryos of diabetic rats showed increased lactate production and content compared to the embryos of normal rats. The embryonic oxidation of glucose decreased slightly from gestational day 10 to day 11, and the embryos of diabetic rats exhibited a lower glucose oxidation rate than those of normal rats on both days. The lactate production and content in the embryos increased with increasing concentrations of glucose in the incubation medium, whereas the oxidation of glucose was unaffected by the glucose concentration. The results suggest that the embryonic metabolism of glucose is only marginally affected by changes in the availability of glucose. The lactate production rate was higher and the glucose oxidation rate lower in the embryos of diabetic than in those of normal rats, even when the values for these metabolic variables were normalized to the embryonic DNA content. Thus, a causative role for a disturbance of the glucose metabolism in diabetes-induced embryonic dysmorphogenesis could be envisaged. PMID- 1414152 TI - Role of the antiglucocorticoid RU 486 in the prevention of steroid-induced hypertension. AB - In the present study, we determined the effect of RU 486 on two experimental models of hypertension in the rat, deoxycorticosterone acetate (DOCA)-salt in nephrectomized rats and spontaneously hypertensive rats. Uni-nephrectomized saline-drinking male Sprague-Dawley rats were divided into three groups and each animal was given either 0.2 ml olive oil (control), 1 mg DOCA, or 1 mg DOCA + 10 mg RU 486 dissolved in 0.2 ml olive oil every third day for a period of three weeks. Within a week of steroid administration, there was a significant increase in the systolic blood pressure (SBP) in the DOCA-salt (157 +/- 3.8 mmHg) and DOCA + RU 486 (155 +/- 2.1 mmHg) treated rats over the control (116 +/- 2.6 mmHg) rats, which remained elevated throughout the experimental period. There was significant increase in the water intake and urine output in DOCA or DOCA + RU 486 treated rats as compared to the control untreated rats. In the experiment involving the spontaneously hypertensive rats, the rats were divided into three groups and each animal given 0.2 ml olive oil (control), 1 mg RU 486, or 5 mg RU 486 dissolved in 0.2 ml olive oil for six weeks. Instead of the expected decrease in the blood pressure, RU 486 significantly elevated blood pressure during the six weeks of drug administration. Water intake, urine output, and weights remained comparable in both groups. We conclude that RU 486 has no effect on the DOCA-salt model of hypertension but, surprisingly, elevates hypertension in the spontaneously hypertensive rats. PMID- 1414153 TI - Multihormonal response to corticotropin-releasing hormone in inferior petrosal sinus blood of one patient with Cushing's disease: comparison with in vitro secretion of the tumoral corticotropes. AB - A multihormonal response to CRH during inferior petrosal sinus sampling in patients with Cushing's disease has recently been described. Whether it reflects multihormonal secretion by the corticotropic adenoma, or secretion by non tumorous adjacent cells via paracrine mechanisms remains debatable. We have compared the effect of CRH on ACTH, GH, PRL and TSH secretion during inferior petrosal sinus sampling with its effect on the in vitro secretion of the corticotropic adenoma after excision in one case of Cushing's disease. Before CRH injection in vivo results show significant central-peripheral gradients for all hormones but only ACTH lateralized to the side of the tumor. After CRH administration, the petrosal concentrations of all hormones increased preferentially on the side of the adenoma resulting in significant intersinus gradients: 8.1 for ACTH, 2.0 for GH, 1.8 for PRL and 1.5 for TSH. In vitro results: the adenoma cells were immunostainable for ACTH only. In culture, they secreted ACTH only. Addition of CRH to the culture induced a mean increase of 160% in ACTH secretion but GH, PRL and TSH remained undetectable. Our results favor the hypothesis that the multihormonal response to CRH seen during inferior petrosal sinus sampling in Cushing's disease reflects a paracrine stimulation of the adjacent non-tumorous pituitary cells by the corticotropic adenoma. PMID- 1414154 TI - HbH disease in Sardinia: molecular, hematological and clinical aspects. AB - In this study we have defined the molecular basis and correlated the clinical phenotype with the alpha-globin genotype in a large series of patients of Sardinian descent with HbH disease. The most prevalent molecular defect was the deletion of 3 alpha-globin structural genes most commonly the (--/-alpha 3.7) genotype (83.6%) and rarely the (--/-alpha 4.2) genotype (1.4%), followed in decreasing order of incidence by the combination of deletion alpha zero thalassemia and initiation codon mutation of the alpha 2-gene (--/alpha NcoI alpha = 9.8%), deletion alpha zero-thalassemia and pentanucleotide deletion of IVS-I of the alpha 2-globin gene, (--/alpha HphI alpha = 3.3%) deletion alpha zero-thalassemia and initiation codon mutation of the alpha 1-gene (--/alpha alpha NcoI = 1.3%), a homozygous state for initiation codon mutation of the alpha 2-gene (alpha Nco alpha/alpha NcoI alpha = 0.7%). Patients with the (--/alpha thal alpha) genotypes showed severer clinical and hematological features as compared to those with the (--/-alpha) or those with the (--/alpha alpha thal) genotypes. The single patient with the (alpha Nco alpha/alpha Nco alpha) genotype had a clinical phenotype intermediate between HbH disease and the alpha thalassemia carrier status. This heterogeneity depends on the fact that the alpha 2-globin gene produces 2-3 times alpha-globin chains than the alpha 1-gene and the single remaining alpha 1-like globin gene in the -alpha 3.7 chromosome has a compensatory increase in the alpha-globin chain output. alpha-Globin gene mapping of HbH disease patients may be useful for predicting the clinical outcome and to improve genetic counseling. PMID- 1414155 TI - Rare inherited bleeding disorders secondary to coagulation factors in Jordan: a nine-year study. AB - This work reports on rare inherited coagulation factors defects which were seen in a developing country over a 9-year period. There were a total of 30 cases which fulfilled this diagnosis. Fibrinogen abnormalities were the most frequently encountered. There were 10 patients with afibrinogenemia, 2 with hypofibrinogenemia and 1 case with dysfibrinogenemia. Factor XI deficiency was found in 7 patients, factor V and VII deficiencies accounted for 3 cases each. Factor X and XIII deficiencies were found in 2 patients each. All these rare deficiencies accounted for 10% of all inherited bleeding disorders in the population studied over 9 years. PMID- 1414156 TI - A randomized placebo-controlled double-blind study of danazol in hemophilia A. AB - A randomized double-blind placebo-controlled crossover trial of danazol was carried out in 19 cases of hemophilia A. Danazol was given for 3 months at a dose of 150 mg/day to patients under 15 years of age, and 300 mg/day to older patients. The basal factor VIII:C level was 8.3 +/- 5.6% (mean +/- SD), and after 3 months of danazol treatment was 15.3 +/- 11.0% (p = 0.02). Six patients (basal factor VIII:C 2-22%) showed a 1.36- to 2.87-fold elevation of factor VIII:C levels after danazol. 0/2, 1/4 and 5/13 cases of severe, moderate and mild disease, respectively, responded. Decreases in the number of bleeding episodes and cryoprecipitate requirement were seen in the responders. No adverse reactions to danazol were encountered. Danazol appears to raise the factor VIII:C levels in selected cases of hemophilia A. PMID- 1414157 TI - Comparison of the proliferative activity and sensitivity to cytosine arabinoside of leukemic blast progenitors in acute myeloblastic leukemia at diagnosis and in relapse. AB - To determine whether the biological characteristics of leukemic cells change after repeated chemotherapy, we compared the proliferative activity and drug sensitivity of leukemic blast progenitors in 7 patients with acute myeloblastic leukemia at diagnosis and in relapse. The proliferative activity of leukemic blast progenitors was assessed based on primary (PE1) and secondary (PE2) colony formation in methylcellulose culture and on the recovery of clonogenic cells in suspension culture. The effect of cytosine arabinoside (Ara-C) on leukemic blast progenitors was studied both in methylcellulose and in suspension cultures. PE1 and PE2 values varied among the patients. PE2 of 4 patients out of 7 patients became significantly higher in relapse than at diagnosis. The sensitivity to Ara C of leukemic blast progenitors deteriorated in 5 patients in relapse. The results suggest that the biological nature in terms of proliferative activity and Ara-C sensitivity of leukemic blast progenitors may change in the clinical course after chemotherapy. PMID- 1414158 TI - In vitro effect of 1,25-dihydroxyvitamin D3 on proliferation and collagen synthesis by bone marrow fibroblasts. AB - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has been used in the treatment of myelofibrosis and beneficial effects have been observed. The mechanism of this effect still remains unclear. The present study examined whether 1,25(OH)2D3 directly affects bone marrow fibroblast proliferation and collagen synthesis. Third to sixth subcultures of rabbit bone marrow fibroblasts were used. 1,25(OH)2D3 exerts dose-related response-inhibitory effects on collagen synthesis. 1,25(OH)2D3 significantly inhibited collagen synthesis at 10(-9) to 10(-7) M, while 25(OH)D3 was not different from controls. Furthermore, 1,25(OH)2D3 exerted its effect on collagen synthesis without affecting cellular proliferation. Both the cellular protein content and tritium-labeled thymidine incorporation after treatment with either 1,25(OH)2D3 or 25(OH)2D3 were not different from controls. PMID- 1414159 TI - Myelofibrosis and systemic lupus erythematosus: reversal of fibrosis with high dose corticosteroid therapy. AB - A case of myelofibrosis in association with systemic lupus erythematosus (SLE) is reported. Acute thrombocytopenia and a bleeding tendency developed in a 24-year old woman with SLE. Bone marrow aspiration was unsuccessful due to myelofibrosis. Pulse therapy with methylprednisolone reversed both thrombocytopenia and myelofibrosis. A review of the literature revealed that the coexistence of SLE and myelofibrosis is a rare occurrence. Only 7 cases, to our knowledge, have ever been reported in detail. The present case is the 3rd in which myelofibrosis was reversed by corticosteroids. PMID- 1414160 TI - Central nervous system expression of a monoclonal paraprotein in a chronic lymphocytic leukemia patient. AB - An unusual complication of chronic lymphocytic leukemia (CLL) is reported. The patient, a 79-year-old man, had a long standing history of CLL, that had been complicated by the development of a Guillain-Barre-like syndrome and a peripheral biclonal gammopathy. The biclonal immunoglobulins identified in the serum were IgM lambda and IgG lambda. The patient's condition progressed and he eventually developed ophthalmologic complications. Cerebrospinal fluid (CSF) obtained during evaluation of his visual dysfunction contained numerous small, mature lymphocytes consistent with the presence of CLL cells in the central nervous system (CNS); immunoperoxidase staining of these cells revealed a monoclonal population. Protein electrophoretic evaluation of the patient's CSF showed a single monoclonal band and immunofixation electrophoresis of the CSF revealed that the immunoglobulin present was IgG lambda. No evidence for the monoclonal IgM paraprotein identified in serum could be appreciated in the CSF by immunofixation. Taken together, these findings strongly implied that there was CNS involvement by the leukemia and this process caused the patient's neurologic symptoms. Furthermore, this study demonstrates that chronic lymphocytic leukemia should also be considered as one of the hematopoietic malignancies associated with monoclonal gammopathies involving the CNS. PMID- 1414161 TI - An unclassified case of congenital dyserythropoietic anaemia with a severe neonatal onset. AB - The case of a 13-year-old child with a congenital dyserythropoietic anaemia (CDA) is reported. A severe anaemia associated with a slight increase in reticulocytes, erythroblastosis, hyperbilirubinaemia, hepatosplenomegaly, generalized oedema and hypoproteinaemia was present at birth. Three exsanguino-transfusions were needed in the first 4 days of life. In the following years a continuous transfusional regimen was maintained in association with a chelating treatment. Bone marrow aspirates showed a striking hyperplasia of the erythroid lineage with ineffective erythropoiesis and changes of erythroblastic nuclei which were double but incompletely separated. Numerous histio-erythroblastic islands were also present. Electron microscopy studies did not show specific alterations of the erythropoietic cells. By a long-term evaluation of the clinical signs and of the haematological data, we came to the conclusion that the case does not fit into any of the three classical categories of CDA. PMID- 1414162 TI - Autoimmune hemolytic anemia presenting in Sezary syndrome. Report of a case and review of the literature. AB - A 52-year-old man, who presented with Sezary syndrome with autoimmune hemolytic anemia (AIHA) and was successfully treated with corticosteroids is reported. Helper function assay determining immunoglobulin confirmed inducer capability of this clonal population. This patient brings to 4 the number of cases of T cell cutaneous lymphoma and AIHA now reported in the English literature, and is the first case of Sezary syndrome and AIHA thus far. PMID- 1414163 TI - A familial case of hyper-IgM immunodeficiency. AB - A 22-year-old male was diagnosed as having immunodeficiency with hyper-IgM based upon recurrent pneumonia, marked elevation of serum IgM and markedly decreased level of IgG. IgG-or IgA-bearing B cells were not detected in peripheral blood while a number and a proportion of peripheral blood T lymphocytes were normal. Peripheral blood lymphocytes from this patient proliferated normally in response to T-independent and T-dependent B cell mitogens, and to T cell mitogens. Furthermore, the same type of dysgammaglobulinemia with increased IgM was found in the patient's father and brother. From these observations, it is suggested that it is a rare case of autosomal dominant or polygenal inheritance of hyper IgM immunodeficiency. PMID- 1414164 TI - High plasma urokinase-type plasminogen activator levels are present in patients with acute nonlymphoblastic leukemia. AB - An exaggerated hemorrhagic syndrome is a characteristic in acute non lymphoblastic leukemia (ANLL) and it determines the patient's outcome. Disseminated intravascular coagulation as a result of a procoagulant factor release and primary hyperfibrinolysis due to plasminogen activators also released by leukemic cells have been implicated in the development of this syndrome. The aim of this work was to evaluate urokinase-type plasminogen activator (u-PA) and related parameters of the fibrinolytic system in 14 ANLL patients. Our results showed an increased u-PA concentration in ANLL patients compared to controls [2.63 (1.61-4.62) vs. 0.95 (0.77-1.48) ng/ml, p < 0.01]. u-PA levels correlated positively with tissue-type plasminogen activator. The relevance of the enhancement of u-PA in this clinical setting was supported by the fact that it was the only analytical parameter positively correlated with patient mortality (p < 0.05). Though u-PA levels do not seem to be the determining factor in the development of the hemorrhagic syndrome of ANLL patients, a contributory role of this plasminogen activator is suggested from our results. PMID- 1414165 TI - [Is it necessary to treat silent myocardial ischemia?]. AB - Since the mid eighties of our century the clinical importance of silent myocardial ischemia, concerning definition, prevalence and pathophysiology is well established. The implication of silent myocardial ischemia, or its combination with other parameters of coronary heart disease on the outcome of ischemic heart disease concerning the endpoints myocardial infarction, myocardial insufficiency or death is still not clear. In consequence therapeutic guidelines at the moment can not be given for the entire spectrum of silent ischemia, whereas some details are becoming more and more evident. PMID- 1414166 TI - [Is it necessary to treat silent myocardial ischemia?]. AB - At the present time there is no firm evidence that silent myocardial ischemia (on exercise or Holter ECG) should be treated with anti-ischemic drugs. Silent ischemic episodes obviously are a marker for ischemic activity of coronary artery disease and therefore a bad prognostic sign. However, antianginal drugs (nitrates, calcium-blockers, beta-blockers) have not been shown to improve prognosis. Patients with ischemic episodes should be further evaluated by thallium scintigraphy and coronary angiography. If a significant coronary disease is present, the established therapy with risk factor reduction, lipid lowering drugs and aspirin should be administered. In some instances PTCA or CABG may be indicated. PMID- 1414167 TI - [Early therapeutic intervention in heart failure]. AB - During the past years, several large trials (Consensus, VHEFT I and II, SOLVD) have shown a significant reduction of mortality in patients with moderate and severe heart failure. However, despite effective treatment with vasodilators, digitalis and diuretics mortality in these patients remains unacceptable high. It seems logic, to state treatment at an earlier stage of the disease to achieve more benefit. The main early pathophysiological disturbance is left ventricular hypertrophy, resulting from hypertension, coronary artery disease, increasing age and obesity. On the long run, LVH may lead to diastolic and systolic heart failure, myocardial ischemia, arrhythmias and sudden death. With ACE-inhibitors LVH can be reduced within 1 month of treatment. The large SAVE- and SOLVD prevention trials will show, whether this early intervention will improve proposis in patients with asymptomatic heart failure. PMID- 1414168 TI - [Effects of treatment of arrhythmias requiring therapy in dilated cardiomyopathy with amiodarone on alpha human atrial natriuretic peptide]. AB - In a longitudinal study comprising a total of 18 patients, the paradoxical time course of hANP plasma levels, i.e. the reproducibility of the low levels previously reported in cases of extreme cardiac insufficiency after administration of amiodarone, was investigated over a period of 9 months. At the same time, the effect of the degree of cardiac insufficiency and arrhythmia on the secretion of hANP was observed. The patients had been admitted to hospital because of the diagnoses "cardiac insufficiency secondary to cardiomyopathy" or "Grade IVb arrhythmia according to Lown's classification". During in-patient treatment, antiarrhythmic therapy was commenced in all patients. Clinical examinations and determinations of humoral parameters during therapy showed a substantial number of patients, who exhibited no increase in hANP levels despite massive cardiac decompensation. As far as drug therapy of patients with severe arrhythmias secondary to congestive (dilated) cardiomyopathy is concerned, amiodarone has proved to be the drug of choice in combination with digitalis, ACE inhibitors and diuretics. There is a close correlation between the degree of cardiac insufficiency and plasma hANP levels. PMID- 1414170 TI - [23rd annual meeting of the Austrian Society for Internal Medicine. Abstracts]. PMID- 1414169 TI - [Abnormal origin of the ramus circumflexus sinister from the left atrium in a 30 year-old patient with aortic isthmus stenosis and atrial septal defect]. AB - In this case report a 30-year-old woman suffering from progressive angina pectoris and dyspnea, having been operated on previously for atrial septum defect at the age of 19 and later aged 24 for coarctation of the aorta, is described. Upon observation, patient showed cardiac symptoms already under mild stress and remained resistant to nitroglycerin. Rest-ECG and serum cardiac enzymes were repeatedly without findings, while stress-ECG at a level of 100 W showed a ST segment depression of 0.15 mV, at the same time complaining of angina pectoris symptoms. Coronary angiography revealed a left circumflex coronary artery arising from the left atrium being fully supplied by the left anterior descendent artery and the right coronary artery via pronounced collaterals, both originating from the ascending aorta. Despite such severe symptoms patient refused surgery suturing the abnormally arising artery. One year following coronary angiography patient is suffering from stabile angina pectoris without occurrence of myocardial infarction or another cardiovascular event. PMID- 1414171 TI - A call to power: transforming attitudes into actions. PMID- 1414172 TI - Reduce, reuse and recycle in the anesthesia workplace. PMID- 1414173 TI - New Jersey's hospital anesthesia standards. PMID- 1414174 TI - AHCPR releases clinical practice guideline on pain management. PMID- 1414175 TI - Postanesthesia care standards, obstetrical anesthesia/analgesia guidelines, and end-tidal carbon dioxide monitoring. PMID- 1414176 TI - Carbon dioxide embolism during laparoscopy: a case report. AB - A 28-year-old female with a diagnosis of multiparity was scheduled for laparoscopic tubal ligation. The patient had an unremarkable medical history, except that she had been a pack-a-day smoker for the past 10 years and had experienced a recent upper respiratory infection. General anesthesia was accomplished without incident, and insufflation of the abdomen with carbon dioxide (CO2) gas was begun. During insufflation the end tidal carbon dioxide (ETCO2) level dropped dramatically, ECG changes were noted, and vital signs deteriorated with the subsequent development of cardiac arrest. The patient was successfully resuscitated, fully awake, and extubated approximately 1 hour after the incident. A CO2 embolus caused by CO2 insufflation was suspected. In laparoscopic procedures, the use of CO2 gas is an efficient and inexpensive means of improving visualization of the abdominal cavity. The effect of CO2 insufflation on the patient should be given special consideration in these cases. Although serious complications associated with the use of CO2 gas are rare, such procedures must not be viewed with complacency. A protocol for the management of emergency situations should be developed and reviewed. PMID- 1414177 TI - AANA journal course: update for nurse anesthetists--managing human immunodeficiency virus and acquired immune deficiency syndrome during anesthesia care. AB - The human immunodeficiency virus (HIV) and its advanced progression to acquired immune deficiency syndrome (AIDS) has had a greater impact on our society than any other disease entity during this century. Throughout the past decade the prevalence of HIV disease has grown to pandemic proportions throughout many regions of the world. The infectious and often fatal nature of HIV has made AIDS the most threatening epidemic currently facing modern medicine. A myriad of fears concerns, challenges, and frustration face all healthcare providers whose awareness and impact on practice is continuously challenged. Every nurse anesthetist is responsible for maintaining the ability to both prevent HIV disease transmission and appropriately care for HIV-infected patients during anesthesia care. Experience throughout the past decade of a continuously increasing prevalence of both HIV and AIDS has provided a wealth of information and knowledge that continues to enhance patient care. The following AANA Journal Course will present a current overview of HIV disease and considerations for providing quality anesthesia care while preventing disease transmission. PMID- 1414178 TI - Attitudes of certified registered nurse anesthetists toward AIDS and AIDS patients. AB - This study was intended to examine and identify the nature of CRNAs' attitudes concerning acquired immune deficiency syndrome (AIDS) and patients with homosexual lifestyles. This research question has been previously addressed using sample populations of registered nurses, physicians, and medical students. This inquiry was conducted using a sample population of nurse anesthetists. The target population was 500 CRNAs who reside in areas of high AIDS incidence--New York City, San Francisco, and Houston. The participants were equally divided among the three cities using a randomized list provided by the AANA. The design for this study was an experimental 2 x 2 factorial with two independent variables: disease of the individual, either leukemia or AIDS, and the sexual preference of the individual, either heterosexual or homosexual. The randomly distributed questionnaire consisted of three scales: the interpersonal attraction inventory, the prejudicial evaluation scale, and the social interaction scale. Multivariate analyses of variance (MANOVA) were conducted not only on the main effects, disease and sexual preference, but also on the interaction effects of disease and sexual preference. The significant findings of the MANOVAs were subjected to factorial analysis for each scale, and then the MANOVAs were conducted again. The statistical analysis indicated that CRNAs possess a negative attitude toward AIDS patients but not toward leukemia patients. Their attitudes are based on their perception that AIDS patients are responsible for their illness. Potential behavioral consequences were also reported by CRNAs, based on these attitudes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414179 TI - The effect of pH-adjusted 2-chloroprocaine on the duration and quality of pain relief with a subsequent continuous epidural bupivacaine infusion. AB - A randomized, double-blind true experimental design with a post-test only was chosen to determine if the addition of sodium bicarbonate to 2-chloroprocaine would result in a longer duration of epidural analgesia, as well as increase the quality of pain relief in stage I parturients receiving a continuous bupivacaine epidural infusion. The experimental group (number (N) = 16) received sodium bicarbonate and 2-chloroprocaine followed by a continuous bupivacaine epidural infusion. The control group (N = 15) received normal saline and 2-chloroprocaine followed by a continuous bupivacaine epidural infusion. Only ASA I or II patients in stage I labor were included in this study. Measures of pain perception were made using a self-report, visual analog scale. Measures also were made of the quality and duration of block over time, the intensity of motor block over time, and the blood pressure over time. The cephalad dermatome level of analgesia was determined by pinprick. A record of the need for a supplemental bolus of local anesthetic to maintain a sensory level of T-10 was also recorded. The mean self perceived level of pain was significantly different for the two groups (P = .024). Moreover, the pattern of self-perceived level of pain over time differs for the two groups in a significant way (P = .023). Additional bolus injections occurred nine times in the control group and six times in the experimental group. The differences were not found to be significant (P > .106). The differences in time and amount of local anesthetic delivered were also found to be trivial (P > .80).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414180 TI - Charleston Area Medical Center scholarship/loan program for nurse anesthesia students. PMID- 1414181 TI - The need for alternative educational pathways in nurse anesthesia education. PMID- 1414182 TI - Midwifery: a designated profession. What next? PMID- 1414183 TI - Pain corner. PMID- 1414184 TI - Help for parents--talking to their children about AIDS. PMID- 1414185 TI - Medical profession stops nurse practitioner's practice: accountability, lawsuit and a PHC opportunity. PMID- 1414186 TI - Health reform--the next step. Notes from the Minister. PMID- 1414187 TI - Nursing in a northern isolated post. PMID- 1414188 TI - You touched me. PMID- 1414190 TI - Future directions in nursing. PMID- 1414189 TI - The nurse as care giver negligence actions: the basic elements. PMID- 1414191 TI - Pain corner. Stop, look ... and listen! PMID- 1414192 TI - Iron overload of the bone marrow by trimethylhexanoyl-ferrocene in rats. AB - Iron-deficient female Wistar rats were fed a diet which contained 0.5% 3,5,5 trimethylhexanoyl (TMH)-ferrocene over a 57-week period. The state of iron deficiency was characterized by means of the absence of stainable iron in the bone marrow. After the first days on the iron-enriched diet, ferritin-containing siderosomes were found, in numerous erythroblasts up to orthochromatic normoblasts and in reticulocytes, i.e. the dispensed iron was used for haemoglobin synthesis. After 1 week the first macrophages showed a positive Perls' Prussian blue reaction. In the cytoplasm they stored the iron in the form of free ferritin molecules and lysosomally as aggregated ferritin and/or haemosiderin. The iron loading of the macrophages increased in both of the storage qualities proportionally with duration of the feeding period and reached a maximum after 38 weeks. Final stages showed extremely iron-loaded macrophages with high concentrations of free ferritin molecules and large siderosomes, partially flowing together to still greater units. Iron deposits within endothelial cells of bone marrow sinusoids can be observed for the first time after 4 weeks. In these cells the iron is stored as ferritin in siderosomes of relatively small and uniform size; free ferritin molecules in the cytosol were of only slight concentration. The TMH-ferrocene model of iron overload shows in the bone marrow: (1) an unimpeded utilization of the iron component for erythropoiesis, (2) development of excessive iron overload of the bone marrow in macrophages and endothelial cells of sinusoids and (3) a pattern of distribution of iron as seen in secondary haemochromatosis. PMID- 1414193 TI - An increase in thymocyte proliferation during pseudopregnancy in two inbred strains of rat. AB - Coitus is a unique physiological event which may result in internal fertilization, whereby active allogeneic spermatozoa are presented to the female host which can invade her tissues. Sterile coitus on the other hand, stimulates the uterine cervix in the rat and induces a physiological state of pseudopregnancy which interrupts the normal pattern of the oestrous cycle and establishes a persistent dioestrous state. This state is hormonally controlled and in its early stages is not dissimilar from that of true pregnancy. Pregnancy hormones are known to influence the immunological status of the female. Thymic observations during early pseudopregnancy showed interstrain differences in weight, cell content and thymocyte proliferation. Pooled data indicated increased cell density on days 3, 4 and 5 of pseudopregnancy associated with a peak of mitotic activity on day 3 in both strains. The timing of this proliferative activity seems to reflect the needs of the immune system in its putative response to mating and implantation. PMID- 1414194 TI - The innervation of the lymphoid tissue at the ileocolonic transition: an enzyme and immunohistochemical study. AB - Using enzyme and immunohistochemical methods on whole-mount preparations and cryostat sections, a morphologic and semiquantitative study was performed of the nervous tissue in the appendix and the ileum (areas with and without Peyer's patches) of the rabbit. The plexus submucous externus (Meissner) consists of a network of small ganglia, vaguely associated with the vascular submucosal plexus. From the nerve cell bodies, cell processes occasionally penetrate the lymphoid follicles at the junction between the mucosa and the submucosa while other extensions form a dense plexus in the lamina propria of the mucosa. No nerve fibers are present in the dome of the follicles. The plexus submucous internus (Henle), consisting of large cell bodies and large processes, closely follows the blood vessels. The numeration of the nerve fibers of the submucosal plexus endorses the histological finding that the appendix is a richly innervated lymphoid organ. In addition, the plexus myentericus (Auerbach) of the appendix is a network of small meshes, while in the ileum, in the area of Peyer's patches, the same plexus is composed of a network with large meshes. These differences point to a higher density of innervation in the appendix. Yet a specialized anatomic distribution of the innervation of lymphoepithelial structures cannot be demonstrated. PMID- 1414195 TI - Weaning and the histology of the mandibular condyle in the rat. AB - Eighty-eight Long Evans/Turku rats were used in the study. The effect of the articulatory function on the mandibular condyle was observed histologically during normal growth, when the rat is changing its diet from milk to whole pellets as a part of weaning. Six animals each were killed at the age of 10, 15, 20, 25, 30, 35, 40 and 50 days for histological tissue processing. For further information, 30 animals were fed a soft diet (6 animals each were killed at the age of 25, 30, 35, 40 and 50 days), and 10 animals were fed hardened pellets (2 animals each were killed at the ages of 25, 30, 35, 40 and 50 days). An even and regular transition from mesenchymal cells via immature chondroblasts into mature chondroblasts and hypertrophied chondrocytes was found at 10, 15 and 20 days during normal growth and also at 25, 30, 35, 40 and 50 days when animals were fed a soft diet. This maturing process appeared to be disturbed at the age of 25, 30, 35 and 40 days in the superior aspect of the condyle in animals fed ordinary pellets. The density of the mesenchymal cell layer was decreased, and the amount of intercellular matrix seemed to be evaluated in mesenchymal and intermediate cell layers. These features were later manifest deeper in the cartilage as acellular regions and as cell clusters. The changes were similar but more severe when the animals were fed hardened pellets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414196 TI - Immunohistochemical study of carbonic anhydrase III in the extraocular muscles of human embryos. AB - The differentiation of extraocular muscles was studied immunohistochemically in externally normal human embryos (Carnegie stages 13-23), using antibodies to carbonic anhydrase (CA) III and beta-enolase as the markers of type 1 and type 2 muscle fibers, respectively. At stage 18, some myoblasts were immunoreactive to beta-enolase antibodies, however, CA-III immunoreactivity was not observed around the optic vesicle. At stage 20, CA-III immunoreactivity appeared in some muscle fibers of extraocular muscles. From stage 21 to stage 23, CA-III-immunoreactive fibers increased and almost equalled the number of beta-enolase-immunoreactive fibers. These findings suggest that CA-III-immunoreactive type 1 fibers appear in the late stage of myogenesis compared with beta-enolase-immunoreactive type 2 fibers. PMID- 1414197 TI - [The origin and distribution of cartilage canals in the chick embryo]. AB - 113 femurs and 111 tibias originating from chick embryos 8-21 days after incubation were injected with Indian ink and made transparent. The origin and distribution of cartilage canals are described. The existence of a pattern of segmental distribution, atypical canals and anastomosis between epiphysial canals and diaphysial marrow processes is reported. PMID- 1414198 TI - Measurements of cross-sectional areas in selected human wrist-joint ligaments. AB - The cross-sectional area of a particular ligament is an important characteristic in order to establish the biomechanical properties of this ligament. Calculations of the cross-sectional areas of the ligaments of the wrist joint are made from two three-dimensional models. It is discussed that differences between the presented and the scarcely published data on cross-sectional areas are the result of different divisions of the wrist-joint ligamentous complex into separate ligaments. PMID- 1414199 TI - How little luteal tissue of rats is needed to maintain pregnancy till term--an experimental verification. AB - Surgical reduction of luteal tissue to about 20% of its total mass on day 5 pc was found to maintain gestation till term. A high degree of fetal loss was, however, evident. An identical surgical manipulation at the end of maximal luteal maturity, that is, on day 16 pc, resulted in normal maintenance of gestation. Fetal growth and their survival rate were found to be comparable to controls. An exclusive surgical extirpation of corpora lutea, on the other hand, either on day 16, 17, 18 or 19 was found to cause 100% fetal loss by day 23. However, progesterone replacement therapy concurrently with surgical luteal ablation till day 20, or surgical extirpation of the entire luteal mass when shifted on day 20, led the pregnancy to term. Present experimental findings, therefore, suggest that only about 20% of the functionally matured luteal mass until day 20 is essentially enough to maintain an ideal pregnancy status till term. PMID- 1414200 TI - Melanocytes--a UV-sensitive neural network and circadian rhythms. AB - The melanocytes are acutely sensitive to a single pulse of UV and express neural differentiation. The present work was undertaken to observe whether the melanocyte can sense variations in the duration of UV exposure. Whole skin organ cultures from marginal zone in vitiligo were exposed to a single pulse of UV, 30, 60, 90 and 120 s each. Catecholoxidase levels in the marginal melanocytes and the volume of melanocytes were used to calculate and quantitate the changes in enzyme production. The melanocytes' dendricity, volume and enzyme production increases with the duration of UV exposure. This sensitivity of the marginal melanocytes, to changes in the duration of UV exposure, simulates the coat color changes in weasels and the polar fox exposed to extreme variations in the day/night cycles. The UV response is associated with proliferation of melanocytes as it is G2-phase dependent. Thus the melanocytes form a UV-sensitive neural network responding to annual changes in the photoperiodicity. PMID- 1414201 TI - Development of the urinary system of the marsupial native cat Dasyurus hallucatus. AB - The development of the mesonephros and metanephros was examined in the marsupial Northern native cat, Dasyurus hallucatus, from birth through to the end of lactation. The mesonephros was present at birth, reached a maximum volume 11 days after birth and had regressed completely by day 30. The metanephros was present on day 2; glomeruli were first seen on day 8, and nephrogenesis continued until day 89 post partum. The newborn native cat is at a very primitive stage of development compared to other marsupials. However, at weaning, like other marsupial species, the native cat has developed a fully morphological and functional urinary system. PMID- 1414202 TI - Morphology of corpuscular receptors in hairy and nonhairy human skin as visualized by an antiserum to protein gene product 9.5 compared to anti-neuron specific enolase and anti-S-100 protein. AB - The present study elucidates the morphology of encapsulated receptors in human skin by means of immunohistochemistry for the recently characterized neurospecific marker protein gene product 9.5, in comparison with neuronal specific enolase and S-100 protein. Only two types of corpuscles are identified, Meissner's corpuscles and simple coiled corpuscles. Moreover, this investigation reveals that though regional specialization may exist with regard to the encapsulated receptor density, the comparison of hairy and nonhairy skin does not reveal important differences. PMID- 1414203 TI - Nerve growth factor receptor-like immunoreactivity in the human spinal cord. AB - Nerve growth factor (NGF) receptor-like immunoreactivity has been demonstrated in the normal human adult spinal cord using the monoclonal antibody ME20.4. Intense immunoreactivity was associated with fibres and terminals in the substantia gelatinosa. In lamina IX the neuropil demonstrated punctate staining, the motor neurons themselves being negative. At thoracic levels occasional neurons of the intermediolateral column cell group were NGF receptor positive. Fine axonal and punctate terminal reactivity was observed in the gracile fasciculus, corresponding to axons in transverse section. Similar, though slightly less dense immunoreactivity was observed in the cuneate fasciculus. The demonstration of NGF receptor immunoreactivity may provide a useful marker of sensory innervation in the human spinal cord. PMID- 1414204 TI - An immunoelectron-microscopical observation of mouse juxtaglomerular cells in the case of experimental hydronephrosis. AB - Changes in juxtaglomerular (JG; renin-containing) cells in experimental hydronephrosis 1 month after ureteral ligation were investigated with immunoelectron-microscopical techniques. Two types of granules, electron dense (D) and lucent (L), were observed. D type granules were labeled more intensely with gold particles than those of L type. Granules intermediate between D and L types and exocytosis of D types were observed. In the cells containing D types exclusively, gold particles were restricted to the granules, whereas in the cells containing both D and L type granules, the particles were scattered throughout the cytoplasmic cytosol. The authors discuss the mechanisms of renin release in JG cells. PMID- 1414205 TI - Lymphoid tissue changes during early syngeneic pregnancy in the RT1u rat. AB - An active immunological response by the female to mating and pregnancy is important, if not essential, to successful reproduction. Alloantigens which have been demonstrated on spermatozoa include histocompatibility antigens. In the enigmatic success of the fetal allograft, the conceptus survives owing to failure of the mother either to initiate or complete the process of rejection. In this study, AO(RT1u/AgB2) female rats were caged with male rats of the same strain. Observations were obtained from the first 5 days of their postcoital period, identifying lymphoid tissue changes which are due to the presence of the ejaculate and early products of conception in the female reproductive tract. A significant increase in intrathymic proliferation by day 3 is thought to be a hormonal effect induced by the cervical stimulation at mating. The postcoital exodus of lymphocytes from the thymus is possibly in response to coitus and induced by the seminal plasma to safeguard the implanting conceptus. PMID- 1414206 TI - Prenatal growth pattern of the human maxilla. AB - Regarding maxillofacial morphogenesis there has been a long debate on the growth of the maxillary structure. Using 120 normal fetal maxillae of gestational ages from 16 to 41 weeks, palatal radiograms and frontal histologic sections were made. We have observed two pairs of accentuated growth areas in the fetal maxillae and named them primary growth centers to formulate the maxillary trapezoid (MT) by radiologic image. The MT is formed by four primary growth centers that are best demonstrated by palatal radiograms of the fetal maxilla as well as by frontal histologic sections. The dimensional increase in the MT during the fetal period is documented and statistically analyzed. From this series of results, we have suggested that the growth centers which demarcate the MT are the basic structures of the developing human maxilla. It was also found that the four primary growth centers are the most active sites for maxilla formation until 20 weeks of gestation and thereafter the growth of the maxilla is enhanced by the participation of the intramembranous bone formation along the periphery. This was in contrast to the central primary growth centers that have already finished maturation in the early fetal period and remain only as a peripherally radiating arrangement of thick trabecular bones. PMID- 1414207 TI - [Post-eruptive formation of the root apex. A scanning electron microscopic study]. AB - During the course of root formation, histologic examination show many pictures; however, the last stage of root formation is not well documented. In this paper, we describe cellular and extracellular components of immature teeth with incompletely formed roots. The odontoblast cells were observed with reticular fibers. The cementoblasts and epithelial cells covered the cementoid tissue. The results are discussed. PMID- 1414208 TI - Ontogeny of afferents to the fetal rat cerebellum. AB - Afferents to the fetal rat cerebellum have been studied in fixed tissue with the fluorescent tracer, 1,1'-dioctadecyl-3,3,3',3'tetramethylindocarbocyanine perchlorate (DiI). The dye was applied to the cerebellar anlage at ages from embryonic day (E) 12 to birth (P0). Central processes of vestibular ganglion cells were found to be the first identifiable afferents to the cerebellum, being present at least by E13 and perhaps as early as E12. Ipsilateral spinocerebellar fibres may be labelled from E15, vestibular nuclei (both ipsi- and contralateral) also from E15, while contralateral inferior olivary nuclei could not be retrogradely labelled until E17. Trigeminocerebellar neurons in the interpolaris subnucleus of the nucleus of the trigeminal spinal tract and neurons of the lateral reticular nucleus were not labelled until E22 and P0, respectively. Finally, contralateral pontine nuclei were retrogradely labelled from the cerebellum after birth. PMID- 1414209 TI - Histological study of the temporomandibular joint capsule: theory of the articular complex. AB - The findings of the histological study of the human temporomandibular joint confirm that the cranium and the lower jaw are jointed by two temporomandibular articular complexes (one on the left and another on the right side), each made up, in turn, of two joints--a condylomeniscal condyloarthrosis and a reciprocally fitting meniscotemporal joint. Both these joints are surrounded by short capsular bands which stretch from the condyle to the meniscus and from the latter to the temporal bone and form the true joint capsules. Longer bands which extend from the condyle to the temporal bone may be regarded as reinforcements passing over two articulations. PMID- 1414210 TI - Morphological, histochemical and immunohistochemical differences between tumorous and adjacent tissues in chemically induced colon cancer in rats. AB - Methods of morphological, histochemical and immunohistochemical analyses were used to further characterize differences between tumourous and adjacent grossly normal tissues in chemically-induced colon cancer in rats. Colon tumors were induced by the treatment of rats with 1,2-dimethylhydrazine or with N-methyl-N' nitro-N-nitrosoguanidine alone or with subsequent treatment with deoxycholic bile acid. Tissues were studied morphologically (for the presence of goblet cells in the colon crypts, and the extent of infiltration of lymphocytes into the crypts and between them), histochemically (for the presence of positive reaction to neutral and acid mucopolysaccharides) and immunohistochemically (for the presence of tissue polypeptide antigen). All data were evaluated quantitatively, and index of tissue damage was calculated for both tumorous and non-tumorous tissues. Significant morphological differences were found between tumorous and adjacent apparently normal tissue. Histochemically and immunohistochemically, both types of tissue reacted very similarly to exposure to the carcinogens. Index of damage was significantly different from normal untreated colon in both kinds of tissue. It was suggested that precancerous state in tissue adjacent-to-tumor could be detected using the combination of these methods. PMID- 1414211 TI - [Histology, immunocytology, histochemistry and muscle fiber innervation of the pectoralis major and supracoracoideus muscles of Excalfactoria chinensis chinensis (L.)]. AB - The morphology of the pectoralis major muscle and its antagonist, the supracoracoideus muscle, of the Chinese quail was studied in comparison with the Japanese quail, in relation to behavioral characteristics. The actomyosin ATPase reaction after alkaline and acid preincubation reveals two fibre types. The indirect immunofluorescence, using specific antibodies against 'slow' (twitch) myosin from the human vastus lateralis muscle, provokes a weak reaction. All fibres observed show focal, monoaxonal 'en plaques' endings, typical of the phasic motor system. For the two quail species, the muscle structure seems adequate in relation to the movement characteristics, meaning muscle activity of migratories, flying long distances. PMID- 1414212 TI - Thenar and hypothenar muscles and their innervation by the ulnar and median nerves in the human hand. AB - The thenar and hypothenar muscles as well as their supplying nerves were analyzed with an improved dissecting method. Among the four thenar muscles, the m. abductor pollicis brevis (AbPB) has a separate muscle belly, whereas the m. opponens pollicis (OP), the superficial and deep heads of the flexor pollicis brevis (sFPB and dFPB), and the adductor pollicis (AdP) are fused with each other to make a single mass (deep thenar muscle group). These muscles are innervated by branches of the recurrent nerve and the accessory recurrent nerve from the median nerve as well as by terminal branches of the deep branch (ramus profundus) of the ulnar nerve. These three nerves frequently form a loop within the deep thenar muscle group (thenar loop), and a branch to the OP and one to deep parts of the sFPB often make a smaller loop (intrathenar loop), whereas the AbPB receives a separate nerve branch. Among the hypothenar muscle, the m. abductor digiti minimi and the m. flexor digiti minimi brevis are fused with each other, and their supplying nerves frequently form a loop in these muscles (intrahypothenar loop), whereas the m. opponens digiti minimi is separated from the others and receives a separate nerve branch. In the distribution pattern of supplying nerves to the thenar and hypothenar muscles, we find regularities in that they branch off in a regular manner from the ulnar and the median nerve, and that nerve branches to those muscles with fused bellies frequently communicate with each other to make loops. PMID- 1414213 TI - Vascularization of the cochlea of the guinea pig: a light- and stereomicroscopic study. PMID- 1414214 TI - Effects of 1 alpha(OH)-vitamin D3 and 24,25(OH)2-vitamin D3 on long bones of glucocorticoid-treated rats. AB - Glucocorticoids may induce osteopenia in experimental animals and in man. In order to study the possible effects of vitamin D metabolites in the prevention of glucocorticoid-induced osteopenia in rats, we administered 1 alpha(OH)-vitamin D3, 24,25(OH)2-vitamin D3 or a combination of both metabolites, by intragastric intubation, to rats treated daily by intramuscular injections of 10 mg/kg cortisone acetate. Treatment with the vitamin D metabolites started after 1 month of glucocorticoid therapy, at the time osteopenia was already present. Cortisone acetate decreased the gain weight, increased alkaline phosphatase (AP) and decreased Ca serum levels. It also decreased tibial wet and ash weight and tibial Ca content. Computerized histomorphometry of sections from the upper tibia showed decreased epiphyseal bone volume and increased bone marrow volume; decreased height of hypertrophic cartilage in the growth plate and decreased amount of persisting cartilage in the metaphyseal bone trabeculae were also observed. Administration of 24,25(OH)2D3 alone did not reduce these glucocorticoid-induced bone changes and sometimes even worsened them. 1 alpha(OH)D3 reversed many of the deleterious effects of cortisone acetate. It reduced serum AP levels, increased serum Ca levels, increased bone ash weight, epiphyseal and metaphyseal bone volume, with a concomitant reduction in epiphyseal and metaphyseal bone marrow volume. The best results were obtained by a combination of 1 alpha(OH)D3 and 24,25(OH)2D3. It is presumed that both metabolites are needed to reduce the impact of glucocorticoids on bone. 1 alpha(OH)2D3 acts on the gut, increasing Ca absorption (which was decreased by glucocorticoids), and 24,25(OH)2D3 directly acts on bone to enhance bone formation and mineralization. PMID- 1414215 TI - Presence of melanin in the cat pineal gland. AB - Light- and electron-microscopic features of pigmented cells in the cat pineal gland are described. These cells were observed throughout postnatal life from the second postnatal day to the oldest cats studied (up to 13 years old). No apparent relationship was observed among the amount of pigment and the animal age or sex. Pigmented cells showed a preferential localization at the ventral surface of the pineal gland near its distal end. The pineal pigment was histochemically identified as melanin. Pineal pigment granules showed ultrastructural features similar to melanocyte melanin granules. PMID- 1414216 TI - Structural characterization of the mandibular condyle in human fetuses: light and electron microscopy studies. AB - Mandibular condyles from 18- to 20-week-old human fetuses were examined in the light and electron microscope with particular attention to intratissue organization and extracellular matrix. In the human fetus the condyle has been divided into five layers: (1) the most superficial, articular layer, (2) chondroprogenitor cell layer, (3) condroblast cell layer, (4) nonmineralized hypertrophic cell layer, and (5) mineralized hypertrophic cell layer. The articular layer is rich in collagen fibers (mostly of the type I collagen), but the cells seldom divide. By contrast, in the chondroprogenitor cell layer and upper part of the chondroblastic cell layer mitosis gives rise to new cells. The matrix in the latter layer is composed of thick banded 'lucent' fibrils in a loose feltwork of granules representing cartilage proteoglycans. The daughter cells in the progenitor cell layer undergo differentiation which is apparently completed along the lower border of the mineralized hypertrophic cell layer--the ossification front. The matrix in the hypertrophic cell layer reveals distinct matrix vesicles that undergo mineralization and subsequently coalesce to form larger sheets of mineralized extracellular matrix. Mineralized cartilage serves as a backbone for new bone formation as marrow-derived osteoblasts and osteoclasts attach to remnants of mineralized cartilage, which enables the turning on of the remodeling cycles involved in new bone formation. It can be concluded that the process of endochondral ossification as has been reported in lower animals is recapitulated in the human fetus, thus the dynamics associated with condylar morphogenesis is maintained through phylogeny. PMID- 1414217 TI - Sensitivity of the fetal rat pituitary-adrenal system to corticotropin-releasing factor in organ culture. AB - Six groups of adrenal glands from 17-day fetal rats were explanted to organ culture for 2 days. In one group, adrenal gland was cultured alone, and in the remaining five groups adrenal gland was cultured with pituitaries from fetuses ranging in age from 14 to 18 days. In each of the groups, half of the cultures had corticotropin-releasing factor (CRF) added to the medium. A histometric parameter utilized the size of adrenocortical cells as an indicator of sensitivity of the pituitary-adrenal system. When 17-day adrenal gland was cultured alone, addition of CRF did not cause any enlargement of cortical cells. When the adrenal gland was cultured with two 14-day pituitaries, cortical cells were enlarged. Addition of CRF to this culture induced no further change. With two 15-day pituitaries in the presence of CRF, cortical cells were slightly larger than those in the absence of CRF. With 16- to 18-day pituitaries, a marked hypertrophy of cortical cells was induced, and the addition of CRF caused further acceleration in their enlargement. These results suggest that, in organ culture, 14-day pituitary can release some adrenocorticotropic hormone (ACTH) with or without additional CRF. Older pituitaries (16- to 18-day) can apparently release an amount of ACTH in the presence of CRF that is greater than their own spontaneous ACTH secretion. PMID- 1414218 TI - Myasthenia gravis in Hong Kong Chinese. 1. Epidemiology and adult disease. AB - A territory-wide study of myasthenia gravis (MG) was conducted in Hong Kong. Two hundred and sixty-two Chinese patients (159 adult and 103 paediatric onset) were identified, corresponding to a point prevalence and period prevalence of 53.5 and 62.2 per million respectively, and an average annual incidence of 4.0 per million population. Nine patients died, 7 from MG, giving a case fatality rate of 0.027. Female predominance was present in the whole group of patients (female to male ratio 1.6:1) and in those with adult disease (ratio 2.1:1), but not in those with onset in childhood (ration 1.1:1). Onset of disease was most common in the first 3 decades of life, and became less common in subsequent decades. Juvenile onset MG occurred in 39.3% of patients and restricted ocular MG in 47.9%. Familial occurrence was found in 5 patients. In the 159 adult onset patients, ocular disease was most common (32.7%), followed by mild generalised (29.6%), moderately severe generalised (24.5%), fulminating (11.9%) and late severe disease (1.3%). The mean age of onset of symptoms was 36.7 years. The symptomatology was similar to that of Caucasoid populations. Autoimmune thyroid disease was the commonest associated disease, and the incidence of thymoma among thymic abnormalities was high at 38%. PMID- 1414219 TI - Absence of interaction between oxcarbazepine and erythromycin. AB - When erythromycin (ERY) is co-administrated with the antiepileptic carbamazepine (CBZ), a drug interaction may cause an increase in CBZ plasma concentrations, which can result in CBZ related toxic symptoms. This cross-over study was designated to investigate whether ERY influences the pharmacokinetics of the new antiepileptic oxcarbazepine (OXC) and its metabolites. In 8 healthy volunteers there were no significant differences in AUC, peak plasma concentrations or time to peak concentration when OXC was administered either with or without ERY. The results of this study suggest that OXC may offer an important advantage over CBZ especially when concomitant therapy with ERY is required. PMID- 1414220 TI - Neuropsychological assessment in MS: clinical, neurophysiological and neuroradiological relationships. AB - We assessed cognitive performance and its relationship with clinical and anatomic disease severity in MS with mild to moderate handicap; 34 definite MS and 18 healthy subjects matched for age and education were submitted to a neuropsychological test battery. Both groups were examined for anxiety. MS patients underwent magnetic resonance imaging examination. MS performed worse than controls on all WAIS-P subtests and had learning, short- and long-term verbal memory impairment. Cognitive deficits were not related to abnormal emotional states, but were found to be associated with attentional process and information-processing speed impairment. Cognitive impairment did not correlate with severity of physical disability. The most severe memory deficits were found in patients with extensive periventricular damage. PMID- 1414221 TI - Humoral CSF parameters in the differential diagnosis of hematologic CNS neoplasia. AB - Cerebrospinal fluid (CSF) and serum samples of 20 patients with central nervous system manifestations of hematological malignancies including primary cerebral lymphoma (n = 5) and disseminated non-Hodgkin lymphoma (n = 7) were examined for albumin, IgG, IgM, fibronectin, beta 2-microglobulin, interleukin-6, soluble interleukin-2 receptor, tumor necrosis factor alpha, and oligoclonal immunoglobulin bands. Although a broad range of abnormalities were detected, no reliable CSF parameter for the diagnosis of leptomeningeal spread from hematological neoplasias could be identified. An analysis of 61 repeat lumbar punctures added little to the findings of the first CSF examinations. Currently, immunochemical studies of CSF cell surface markers and early biopsy have probably more clinical value than the determination of the humoral CSF parameters included in this study. However, analysis of cytokine synthesis by single CSF cells using molecular biology techniques may improve the differential diagnosis of hematological neoplasia of the brain and spinal cord in the future. PMID- 1414222 TI - First seizure in adults: a prospective study from the emergency department. AB - A prospective study of 98 consecutive adults with a first seizure to determine the most important etiological factors and the optimum diagnostics. 27 were thought to have cryptogenic seizures. Main causes of symptomatic seizures were: cerebral infarction, alcohol-withdrawal, CNS infections, tumors, vascular malformations, traumatism and miscellanea. Eight were infected by human immunodeficiency virus (HIV-1) representing 8.2% of all the patients with a first seizure and 20% of the 15-45-year age group. CT disclosed structural lesions in 33 cases. MRI in those with normal CT and no other explanation of seizure revealed additional lesions in 22.2%, but did not change management in any. We conclude that CT is essential in evaluation of adults with first seizure. MRI may be useful in selected cases. The HIV-infected now represent an important group with a first seizure. PMID- 1414223 TI - Nocturnal prolactin and growth hormone levels in children with complex partial and generalized tonic-clonic seizures. AB - This study measures whether there is a rise in the secretion of nocturnal prolactin and growth hormone (GH), during the delta phase of the first sleep cycle in children who are suffering from either complex partial or generalized tonic-clonic seizures. The findings are compared with those obtained in the control group of patients which is made up who suffer from pseudoseizures. There is a moderate but significant rise in the nocturnal prolactin plasma level in both types of infantile seizures. No significant difference was found in the GH. PMID- 1414224 TI - Aging and spectral analysis of EEG in normal subjects: a link to memory and CSF AChE. AB - We studied the effect of aging on EEG spectra recorded from T5-O1 (T6-O2) derivation. The aging series composed of 52 normal individuals aged 20 to 91 years. Seventy-nine per cent of visual and 81% of quantitative EEGs were considered normal. The absolute amplitude of delta and theta bands and absolute power of delta band were lower for the oldest group (aged 60 and over) than for the youngest group (aged 20-39 years). Age was inversely related to the amount of delta and theta indicating that the amount of slow activity in quantitative EEG does not increase with age in the context of good health status. Women had more beta activity compared with men. In addition, the amount of beta and alpha bands showed tendency for a reduction with age. Fifteen subjects aged 50 years or older participated in a 2-year follow-up including EEG and neuropsychological evaluation. Seven of them deteriorated in learning ability and showed increase in delta activity. In the oldest age group, delta amplitude was positively correlated with intrusion errors in the list learning test and inversely related to acetylcholinesterase activity of the CSF. Thus, a link between the cholinergic system, EEG slowing and memory problems in old age is suggested. PMID- 1414225 TI - Elevation of serum ceruloplasmin levels in brain tumours. AB - Serum ceruloplasmin levels have been estimated in 80 patients with various intracranial space occupying lesions and in 30 controls. The ceruloplasmin levels were significantly increased in all brain tumours except in meningiomas. After therapy, the ceruloplasmin levels were still significantly increased when compared to controls and their respective preoperative values. However, the rise in levels of ceruloplasmin in malignant tumours compared to benign was statistically not significant. It is concluded that ceruloplasmin may have a role to play as an acute phase reactant protein in brain tumours. PMID- 1414226 TI - Debrisoquine hydroxylation in Parkinson's disease. AB - Debrisoquine (DBQ) metabolism was studied in 80 Parkinson's disease (PD) patients, 26 of whom had young onset Parkinson's disease (YOPD), and in 143 controls. There was no significant difference between the proportion of poor metabolisers of DBQ among YOPD patients compared either to other parkinsonians, or to controls. Nor was there a significant correlation between the age of disease onset and DBQ metabolic ratio (MR). The results do not support the suggestion that impairment of DBQ metabolism (and hence cytochrome P450) is a primary defect in YOPD. However, in comparison with controls, MR values were modestly but significantly higher in PD patients, even in those not treated with drugs known to affect DBQ metabolism. PMID- 1414227 TI - Effects of withdrawal of phenytoin on cognitive and psychomotor functions in hospitalized epileptic patients on polytherapy. AB - The effects of the withdrawal of phenytoin (PT) on cognitive and psychomotor functions of long-term patients in an epilepsy centre were studied. The patients had been treated for many years (31.1 +/- 10.8 yrs.) with PT in combination with other antiepileptic drugs. The serum concentration of PT was in the lower to middle therapeutic range (6.8 +/- 3.1 mg/l). Only patients in which the efficacy of PT was questionable were included in the study. PT was withdrawn in 17 patients. The PT dose was not changed in 12 patients (control group). Psychological tests were carried out immediately before the withdrawal of PT and about 10 weeks later. Tests were also carried out with the control group at the same time. A significantly improved performance (using a composite score) was noted after the withdrawal of PT. The statistical evaluation of the different tests showed an significant improvement in one test of concentration and two tests of psychomotor function (tapping and pursuit rotor with the dominant hand). There was no significant change in the frequency of seizures. PMID- 1414228 TI - Intravenous gamma globulin in progressive MS. AB - In an attempt to prevent disease exacerbations, intravenous gamma globulin (500 mg to 2 g/kg) plus methylprednisolone was administered monthly to 14 patients with progressive multiple sclerosis, 11 of whom were steroid dependent. Seventeen exacerbations of disease activity were seen in 11 patients over a mean follow-up period of 7.8 months. Four exacerbations occurred in 3 patients within one month of receiving 1.6 to 2.0 g/kg of intravenous gamma globulin (IVGG). Most exacerbations occurred within 2 weeks of steroids being tapered; thus a steroid sparing effect of IVGG could not be demonstrated. We conclude that IVGG plus methylprednisolone can be given safely at monthly intervals for a prolonged period but in the dosage administered did not prevent exacerbations in 80% of patients with progressive multiple sclerosis. PMID- 1414229 TI - Oscillatory activity in different motor subsystems in palatal myoclonus. A case report. AB - In a patient with palatal myoclonus the mutual interaction between voluntary movements and the myoclonic activity was analysed. Amplitude and frequency of myoclonic activity in hand muscles were modulated by flexions and extensions. A 1:1 relationship was found between EMG-bursts in hand muscles and palatal movements. A 1:2 relationship was found between eye and finger movements. Resetting of myoclonus in the abductor digiti minimi muscle occurred after cutaneous ulnar nerve stimulation. It is suggested that feedback plays an important role in the generation of the oscillatory activity in PM in addition to pacemaker activity in brainstem neurons. PMID- 1414230 TI - Ex vivo release of eicosanoids after aneurysmal subarachnoid hemorrhage: a preliminary experience in humans. AB - Authors addressed the question whether the byosynthesis and the release of specific eicosanoids may occur in human brain cortex, and if the qualitative pattern of arachidonic acid metabolism is similar to that observed in experimental SAH. Human brain samples from 18 patients operated on for anterior communicating artery aneurysm (5 unruptured aneurysms considered as control cases, 7 patients operated on between Days 1 and 4 after SAH and 6 patients operated on between Days 10 and 14) were studied for the ex vivo release of 4 selected eicosanoids (Prostaglandin D2, E2, 6-keto-PGF1a and Leukotriene C4). Levels of arachidonate metabolites were determined by radioimmunoassay technique. PGD2 release is significantly lower in cases operated on delayed phase if compared to both control cases (p less than 0.05) and patients operated on in the acute phase, while there is no significant difference between the release of PGD2 in control cases and patients operated on in the acute phase. Release of 6-keto PGF1a is significantly higher in patients operated on in a delayed phase (p less than 0.03 vs patients operated on in the acute phase and p less than 0.05 versus control cases). The release of LTC4 is significantly enhanced (p less than 0.05) in cases operated on in the acute phase if compared with unruptured aneurysms. The release of PGE2 is significantly enhanced in patients operated on in the acute phase (p less than 0.05) if compared to patients with unruptured aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414231 TI - Early and late outcome in head injury patients with radiological evidence of brain damage. AB - This study examined the early and late outcome in head injury patients with focal or multifocal (unilateral or bilateral) brain contusions revealed by computerized tomography (CT) scanning. The outcome was also evaluated in patients hospitalized due to brain concussion. Three months after the injury (the early outcome) 43% of the 86 cases with multifocal contusions on the CT scan were dead. As evaluated by the Glasgow Outcome Scale, all the 57 patients with a focal brain contusion, as well as the 117 cases with brain concussion, made a good recovery or were moderately disabled. The late outcome (1 to 5 years after injury) was evaluated in 78 cases with brain contusion and in 85 cases with brain concussion, and revealed that complaints and impaired adaptive functioning were frequent in both the contusion and concussion group. The occurrence of headache, dizziness and sleep problems did not significantly differ among the various head injury groups. However, focal or multifocal brain contusions on the CT scan increased the frequency of impaired memory, impaired concentration, speech problems, weakness in arms or legs and seizures with loss of consciousness. Cognitive deficits and speech problems were particularly common in patients with a focal contusion in the temporal lobe. The late adaptive and social functioning were most markedly impaired in cases with multifocal bilateral contusions. PMID- 1414232 TI - Platelet-activating factor acetylhydrolase activity in red blood cell-stroma from patients with cerebral thrombosis. AB - Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) is a bioactive phospholipid and inactivated by a specific enzyme, PAF acetylhydrolase (PAF-AH). We have measured PAF-AH activity in red blood cells (RBCs) from patients with a history of cerebral thrombosis and age-matched healthy controls. The activities in 34 patients and 34 controls were 1.29 +/- 0.28 and 1.64 +/- 0.26 nmol/10(9) RBCs/min (or, 30.0 +/- 5.8 and 35.1 +/- 4.7 nmol/g protein/min) (mean +/- SD), respectively, and the difference was significant (p less than 0.001). In patients, RBC PAF-AH activity correlated positively with RBC filterability, an index of RBC deformability (r = +0.501, p less than 0.05). The RBC activity may play a role in scavenging oxidation products of membrane phospholipids. Lower RBC PAF-AH activity may predispose to ischemic diseases by disturbing microcirculatory behavior of the RBCs. PMID- 1414233 TI - Clinical-radiographic correlations within the first five hours of cerebral infarction. AB - Fifty patients, ages 54-79, with ischemic hemispheric strokes productive of hemiparesis, at a minimum, underwent standardized neurological evaluations, computed tomographic scanning and cerebral angiography (N = 38) or carotid ultrasound (N = 12) within 5 h of onset. A second scan was performed at 5-7 days. Clinical scores were not associated with a history of, or the presence of: hypertension, smoking or cardiac disease, including atrial fibrillation, nor with severe internal carotid artery stenosis or occlusion. Clinical scores were adversely affected by early scan abnormalities (especially mass effect), lesion size, intracranial arterial occlusions, elevated serum glucose levels and the subsequent development of hemorrhagic infarction. Glucose levels correlated with infarct size and the development of hemorrhagic infarction. Delayed intracranial arterial filling and collateral flow were associated with reduced infarct size but did not confer clinical protection. We believe that combining the initial glucose level and scan results has prognostic significance, and early angiography is valuable in characterizing infarct etiology and assessing clinical severity. PMID- 1414234 TI - Chorea gravidarum and chorea associated with oral contraceptives--diseases due to antiphospholipid antibodies? AB - A woman with chorea gravidarum in the absence of SLE is described. She later developed severe chorea while using the contraceptive pill, and high titered antiphospholipid antibodies were detected in serum. A rapid recovery after high dose i.v. methylprednisolone was observed. Deterioration occurred in a later pregnancy. PMID- 1414235 TI - Incidence of transient global amnesia in a Alcoi (Spain) PMID- 1414236 TI - Pregnancy in multiple sclerosis. PMID- 1414237 TI - Stretch reflex of quadriceps femoris and its relation to rigidity in Parkinson's disease. AB - Much evidence suggests that parkinsonian rigidity is due to hyperactivity of a reflex arc. While tendon jerk and H reflex are not modified in Parkinson's disease (PD), the long-latency component of stretch reflex (LLR) shows an increased size in PD. It has been proposed that this modification could account for rigidity. We studied in 14 PD patients and 8 normal subjects the stretch reflex of the quadriceps femoris. The muscle was stretched by a torque motor in two experimental sets: at rest and with voluntary background activity. Latency, duration and size of the reflex were compared in two groups; correlation between size of the reflex and rigidity was investigated. A lower threshold for the reflex was found in PD patients in trials at rest, and LLR showed increased size and duration in trials with background activity. No clear relationships between these data and rigidity were demonstrated. PMID- 1414238 TI - Epidemic of acute inflammatory myopathy in Karnataka, south India: 30 cases. AB - Thirty patients of acute inflammatory myopathy were seen over a short period of 11 months (February to December 1986) at NIMHANS, Bangalore, South India. The characteristic features were: short febrile illness followed a few days later by myalgia, edema of extremities, severe motor weakness and involvement of multiple other systems. Their mean age was 32.3 years and M:F ratio was 4:1. CK levels were increased in all. EMG done in 23 patients showed spontaneous activity in 13 and myopathic pattern in all. Nerve conduction studies revealed abnormalities in 12 cases. Muscle biopsy done in 21 patients showed varying degree of myophagocytosis and inflammatory infiltrates. All patients received steroids for only 6-8 weeks. Twenty-two patients recovered, one developed residual disability and 7 patients died during the acute phase. None of the survivors has developed relapse so far. Such cases with monophasic illness in clusters have not been reported earlier. PMID- 1414239 TI - Oxiracetam in dementia: a double-blind, placebo-controlled study. AB - A multicentre, double-blind, between-patient study was carried out to evaluate the efficacy and tolerability of oxiracetam (800 mg tablet), in comparison with placebo, each given twice daily for 12 weeks to patients suffering from primary degenerative, multi-infarct or mixed dementia. Efficacy was assessed by a neuropsychological battery (simple reaction time, controlled associations, short story, Raven's Progressive Matrices, token test, digit span, word list learning), administered at the beginning and at the end of the study, and by a quality of life scale, administered at entry and after 6 and 12 weeks treatment. Sixty-five patients (28 men, 37 women, mean age 71 yrs) were enrolled; 58 completed the study: 2 on oxiracetam were withdrawn because of poor tolerability, 2 (one in each group) were withdrawn for poor compliance, one (on oxiracetam) for the occurrence of a transient ischaemic attack (defined as not related to the treatment) and 2 for administrative reasons. A significantly (p < 0.01) different effect in favour of oxiracetam was observed on the quality of life scale, and confirmed by significant (defined according to the Bonferroni technique) differences in some neuropsychological tests (e.g. controlled associations, short story). Four patients in the oxiracetam group complained of a total of 5 unwanted effects, and 1 on placebo complained of 3 unwanted effects, but none of them was withdrawn from the study. PMID- 1414240 TI - Slowed reaction time in asymptomatic HIV-positive patients. AB - A total of 24 asymptomatic HIV-infected patients (CDC II/III) and 27 HIV-negative controls were tested for speed of reaction and for general neuropsychological functioning. Reaction time was assessed with two computerized tests with differing levels of cognitive complexity. The results show that the asymptomatic HIV-positive patients have a significantly longer mean reaction time to simple and complex stimuli (SRT p < 0.001, CPT p < 0.05), and a significantly greater standard deviation (SD) (SRT-SD p < 0.005). No significant differences were observed on any of the clinical neuropsychological tests, or in the number of false positive (FP) or non-responses to stimuli (NR) from the CPT. The results indicate that asymptomatic HIV-infected patients are slower and have a greater intra-subject variability in speed using a simple test for reaction time. The difference is less pronounced when doing a more demanding cognitive task and not significant in a test of visuo-motor coordination or on other clinical neuropsychological tests. Emotional state or cognitive strategies affecting speed/accuracy trade-off do not account for the findings. PMID- 1414241 TI - Six-year follow-up study on the efficacy and safety of vigabatrin in patients with epilepsy. AB - Twenty-five patients with epilepsy (mostly with partial seizures) who had responded favourably to a short-term trial of add-on vigabatrin entered maintenance treatment. After 52 to 78 months, 15 patients continue to take the drug with good therapeutic response. Median monthly seizure frequency during the last 2 months on vigabatrin in all patients, including drop-outs, was 3.5 (range 0-74) as compared with 10 (range 3-98) during an initial placebo period (p < 0.01). Drop-outs were caused by adverse events in 2 cases (ataxia and psychotic symptoms respectively), seizure breakthrough in 4 cases and reasons unrelated to treatment in 4 patients. In most patients, side effects were absent or mild, the most frequent complaint being weight gain. It is concluded that the antiepileptic efficacy and good clinical tolerability of vigabatrin are generally maintained during long-term treatment for up to 6 years. PMID- 1414242 TI - Effect of torasemide on intracranial pressure, mean systemic arterial pressure and cerebral perfusion pressure in experimental brain edema of the rat. AB - The study was performed to establish whether a lipophilic loop diuretic, torasemide could modify intracranial pressure and cytotoxic brain edema. Brain edema was induced by water intoxication in nephrectomized rats. Following intravenous injection of 100 mg torasemide/kg body weight at 50, 60, 70, 90 and 120 min, a significant decrease of intracranial pressure was observed. PMID- 1414243 TI - Immunosuppression by whole-body irradiation and its effect on oedema in experimental cerebral ischaemia. AB - The effect of global immunosuppression by sublethal whole body X-irradiation on the development of cerebral oedema was assessed 24 h after right middle cerebral artery occlusion in the rat. Irradiation produced a significant leukopenia and thrombocytopaenia, and significantly reduced cortical oedema when compared to non irradiated control animals. PMID- 1414244 TI - Five different tests of reaction time evaluated in HIV seropositive men. AB - In an attempt to develop a short neuropsychological test battery five different tests of reaction time were assessed according to their ability to discriminate between HIV seropositive men and healthy controls. In all tests a patient group with clinical symptoms was slower than the control group. In the complex reaction time test, which has a large cognitive aspect, even a clinically "asymptomatic" group was slower than the control group. The movement test, a new test with a large motor component, identified most slow responders, defining approximately half of the patients with clinical symptoms and one third of the "asymptomatic" patients as such. A test battery consisting of three tests is suggested for serial assessment and screening. PMID- 1414245 TI - CT-scanning and magnetic resonance imaging in idiopathic spasmodic torticollis. AB - Twenty-five consecutive patients with idiopathic spasmodic torticollis (IST) were investigated with computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain. In only six patients (24%) did CT or MRI reveal brain pathology (focal cortical atrophy and lacunary infarcts). No consistent pathological pattern was detected. Consequently, CT and MRI of the brain provides little diagnostic information in this disorder. PMID- 1414246 TI - Radiological assessment of stenosis of the internal carotid artery at the junction with the common. AB - Stenoses at the origin of 100 internal carotid arteries from patients with ischemic cerebrovascular disease were studied by intra-arterial angiography. Three principles were employed to evaluate the degree of stenosis: 1) verbal description, grading stenoses as mild, moderate of severe, 2) estimation of the true residual diameter, and 3) calculation of percent stenosis, defined here as the diameter of the artery at the origin relative to that at the level of the angle of the mandible. The true diameter, estimated to the nearest whole mm, corresponded well with the verbal description, and correlated significantly with percent stenosis. Since the true diameter is precisely defined, easy to estimate, and directly related to its hemodynamic effect, we suggest that this simple parameter, rather than the more commonly used, but more vaguely defined term "percent lumen reduction", is used to grade stenoses of the internal carotid artery. PMID- 1414247 TI - Carbamyl phosphate synthetase-1 deficiency discovered after valproic acid-induced coma. AB - Valproic acid induced coma is presented in an adult patient without a history of metabolic disease. Liver biopsy revealed a reduction in activity of carbamyl phosphate synthetase-I, an enzyme obligated for transformation of ammonia to urea in the urea cycle. After recovery CT scan follow-up showed marked cerebral atrophy which did not exist prior to the state of coma. Risk factors are discussed. PMID- 1414248 TI - Early onset MS under the age of 16: clinical and paraclinical features. AB - MS in juvenile patients under the age of 16 occurred in 31 (5%) of our whole MS population of 620 patients in the time from 1975-1991. It does not differ clinically from the disease as observed in 72 patients with later onset MS in respect to symptoms at onset, course, progression rate, rate of relapses and abnormalities in CSF and MRI. However, fever, headache, nausea and vomiting with pleocytosis in CSF during the first episode and development of oligoclonal bands with passage of time may be characteristic in some juvenile patients. The presence of oligoclonal bands and MRI results are of high diagnostic value in this special group of patients. PMID- 1414249 TI - Cortical metabolism in posterolateral thalamic stroke: PET study. AB - In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the 18F-fluorodeoxyglucose or the 15O-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the "non-specific" thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain. PMID- 1414250 TI - Large striatocapsular infarcts: clinical presentation and pathogenesis in comparison with lacunar and cortical infarcts. AB - In a well-defined prospective series of 247 patients with a first-ever supratentorial brain infarct, 15 patients (6%; 95% confidence interval 3-9%) had a large striatocapsular infarct. Twelve (80%) had signs of cortical dysfunction, whereas risk factor profile, frequency of significant carotid stenosis, and frequency of potential cardioembolic sources did not differ between patients with striatocapsular and those with cortical infarction. However, patients with striatocapsular infarction more frequently had potential cardioembolic source and significant carotid stenosis than patients with lacunar infarction. Our findings show that large striatocapsular infarcts differ from lacunar infarcts with regard to both presenting signs and symptoms, and pathogenesis, whereas they resemble infarcts involving the cortex. Such patients should therefore be managed and treated as patients with cortical infarction. PMID- 1414251 TI - Anticardiolipin antibodies, a disease marker for ischemic cerebrovascular events in a younger patient population? AB - The prevalence of anticardiolipin antibodies (ACLA) in sera of 49 patients having had their first TIA or ischemic stroke before 50 years of age was studied using a solid phase enzyme immunosorbent assay (ELISA). Five patients had IgM antibodies, eight had IgG, and three had antibodies belonging to both classes. Although ACLA were detected in 32% of patients (95% confidence interval [CI] 19-45%), the ACLA positive group did not differ with respect to clinical characteristics and distribution of major stroke risk factor frequency from the ACLA negative group. Further investigations are needed to establish the role of ACLA in the pathogenesis of ischemic cerebrovascular diseases. PMID- 1414252 TI - Local intraarterial thrombolysis for acute stroke in the carotid artery territories. AB - We have tested the feasibility of local intraarterial thrombolytic therapy in ischemic stroke in the carotid artery territories observed within 5 h of the onset of symptoms. Only 5 of 615 consecutive patients were enrolled. They were 1 man and 4 women aged 50 to 75 years. Angiography disclosed occlusion of the M2 tract in one, of the M3 tract in one, of the carotid siphon in one of M4 tract in two. Intraarterial urokinase was infused at a mean dosage of 560,000 units close to the site of occlusion. Four of them had partial or complete recanalisation at early angiographic control and were independent at 6th month control. The one who did not demonstrate recanalisation was confined to a wheelchair. One patient, who had recanalisation, sustained a hemorrhagic transformation of the brain ischemia not interfering with outcome. Our experience, at the light of the low rate of enrollment, despite the results, suggest that intraarterial thrombolysis may be a therapeutic tool for selected patients with stroke in the carotid artery territories and not a routinary treatment for them. PMID- 1414253 TI - Inhibition of the startle reaction by physostigmine in patients with early brain damage. AB - The influence of physostigmine and atropine on the startle reaction and EEG epileptic paroxysmal activity was examined in 24 severely impaired children with early brain damage. The startle motor reaction could be regularly evoked by tapping on the sternum in 12 of the patients. Physostigmine inhibited this reaction significantly, while atropine was without effect. In 12 patients without a previous startle reaction, atropine had a possible activating effect, however, the result was not significant. Physostigmine had no effect. The EEG paroxysmal activity was inhibited by physostigmine and activated by atropine in both groups of patients. A cholinergic system disturbance was suggested in the pathophysiology of the paroxysmal activity. The disturbance which is probably present in early brain damage, is presumed to be also involved in the genesis of the startle reaction. PMID- 1414254 TI - Correlation of magnetic resonance imaging and CSF findings in patients with acute monosymptomatic optic neuritis. AB - Acute monosymptomatic optic neuritis (AMON) may be the first indication of multiple sclerosis (MS), and this sign offers a special opportunity to study the very early clinical stages of MS. This prospective investigation compares results of CSF findings and magnetic resonance imaging (MRI) in a large, homogeneous and well-defined group of patients with AMON. Of 68 consecutively referred patients, 11 had clinically definite MS, another 5 refused a lumbar puncture, and 7 could not participate for various reasons. With the remaining 45 untreated patients, aged 12-52 (mean 31) years, with idiopathic AMON, we have studied interrelationships of CSF findings (leucocyte count, IgG-index and in 29 of the patients oligoclonal bands (OB)) and MRI. Lumbar puncture and MRI were performed within median 24 and 16 days of onset, respectively. In the CSF one or more abnormalities (in 17/45 = 38% pleocytosis, in 16/45 = 36% increased IgG-index, and in 20/29 = 69% OB) was found in a total of 23/29 = 79% of patients. MRI at 1.5 T (double SE and IR sequences) showed multiple cerebral lesions in 65% of patients. A significant relation was observed between results of MRI and leucocyte count (p < 0.05) and between results of MRI and IgG-index (p < 0.05), but not between results of MRI and OB (p > 0.20). Over a median observation period of 27 months, 13 patients developed clinically definite MS. All of these patients had lesions on MRI at onset, illustrating the prognostic importance of MRI findings. Results of CSF had until now no marked predictive value for developing clinically definite MS. PMID- 1414255 TI - Remission rate after thymectomy in myasthenia gravis when the bias of immunosuppressive therapy is eliminated. AB - The clinical course of all 86 myasthenia gravis (MG) patients who were thymectomized at Sahlgrenska Hospital between 1955 and 1980 was evaluated in order to estimate what the rate of complete clinical remission (with or without anticholinesterase medication) would be without immunosuppressive (IS) therapy; 19 of 73 patients without thymoma received IS therapy. A suitable way of dissociating the course after thymectomy from the influence of IS therapy is the Markov method. The calculated probability of remission was 0.18, 0.35, 0.43, 0.53 and 0.56 in the 0-1, 2-3, 4-5, 5-10 and more than 10-year periods after thymectomy. A similar result (53 +/- 7%) was obtained by a life-table method with censoring of IS-treated patients when they received such therapy. Time to remission was significantly shorter for patients with age of MG onset before 35 years. Timing of IS therapy after thymectomy is discussed, considering the post thymectomy remission rate. PMID- 1414256 TI - Impaired blood superoxide dismutase in the traumatic paraplegic patients. AB - Blood superoxide dismutase (SOD) activity and blood copper, zinc-superoxide dismutase (Cu.Zn-SOD) content were measured by luminol chemiluminescence assay and by single radial immunodiffusion assay, respectively, in 50 patients with paraplegia due to traumatic injury to the spinal cord by the Tangshan Earthquake on July 28, 1976, compared with 20 age-matched healthy subjects. We found that blood SOD activity and blood Cu.Zn-SOD content in the paraplegic patients were significantly lower than those in healthy subjects (p < 0.01). In healthy subjects, blood Cu.Zn-SOD fully expressed the enzymatic activity, whereas only 77% of blood Cu.Zn-SOD in the paraplegic patients expressed the enzymatic activity, indicating that in the patients, part of blood Cu.Zn-SOD protein is in a state without function. Also the serum lipid peroxide level in the paraplegic patients was higher than that in healthy subjects (p < 0.05). These findings suggest decreased endogenous blood protection against oxygen derived free radicals in these paraplegic patients. PMID- 1414257 TI - Estimating neuron dendritic length in 3D from total vertical projections and from vertical slices. AB - The recently developed method of total vertical projections is illustrated to estimate the total dendritic length of a human Substantia Nigra neuron. Next, the length of the different orders of dendritic branches, and the mean segment length for each order--commonly regarded as important parameters in neuron physiology- are also estimated. Finally, it is shown how to estimate the mean dendritic length in a population of neurons from vertical slices of arbitrary and unknown thickness. Being unbiased and highly efficient, the proposed methods offer interesting alternatives to current procedures used for the metric analysis of neuron arborizations. PMID- 1414258 TI - Stereological quantitation of human brains from normal and schizophrenic individuals. AB - The complex organization and high density of nerve cells in the human brain presents a challenge to the estimation of total cell numbers. The first unbiased counting method, the disector, was described in 1984 and has since made it possible to accurately count total neuron numbers in any region that can be defined, while excluding artifacts of earlier counting methods. The disector method has been applied to normal neocortex and to four subcortical brain regions from schizophrenics and controls. The total neuron number in neocortex in 26 normal individuals was estimated to be 25.10(9). A 40 and 50% reduction of total nerve cell number was found in the mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics, respectively. Furthermore, the Cavalieri principle has been used to estimate the volume of human cortex, white matter, central grey regions and the volume of the ventricular system in both controls and schizophrenics. As shown by these studies, the introduction of unbiased stereological methods and subsequent modifications in recent years have made it possible to estimate a number of parameters in the human brain without the biases included in most classical works. By comparison, earlier conventional counting methods have been relatively time consuming, mostly biased to a smaller or larger degree, and generally less precise. The application of these new neurostereological methods will undoubtedly provide greater confidence for future brain studies. PMID- 1414259 TI - Estimation of the total number of neurons in different brain areas in the Mongolian gerbil: a model of experimental ischemia. AB - The quantitative stereological method is applied to a study of the number of neurons in three different areas in the brains of an animal model, the Mongolian gerbil. The simplicity and accuracy of the method is emphasized. The usefulness of the method and the model is mentioned especially focusing on the major disabling disease in the Western world today, cerebrovascular disorders. Some results are presented to give an idea of the maximum number of neurons in these animals within the delineation of the brain areas here applied. PMID- 1414260 TI - Mean volume of pigmented neurons in the substantia nigra in Parkinson's disease. AB - A new unbiased stereological estimator, the rotator, was used to estimate the mean volume of pigmented substantia nigra (SN) neurons in three Parkinson's disease (PD) brains and age-matched controls. Average pigmented neuron volume was 31,300 microns 3 (5200) in controls and 28900 microns 3 (120) in patients. Estimating the absolute size distribution, revealed that PD patients had approximately 80% less total SN pigmented volume than controls. Compared with biased methods, in addition to dramatic improvements in efficiency and accuracy, results obtained by the unbiased rotator suggest that primarily the largest pigmented neurons in SN are lost in PD. PMID- 1414261 TI - The aging brain. AB - A recent interest in aging of the nervous system is related to the remarkable increase in the numbers of elderly persons throughout the world. As a reflection of the added years, pathologies in the older person have also increased. Primary among those which affect the activities and behavior of these people are the dementias, especially Alzheimer's Disease. To focus on such problems, however, requires an understanding of the changes which take place in the normal aging nervous system. This paper reviews some of the accepted criteria for these changes as well as the possible attempts by the nervous system to alter its structure in response to these changes. PMID- 1414262 TI - Quantitative neuropathology in epilepsy. AB - Counting of neurons has brought new insight to the mechanism of epilepsy. The reduction in Purkinje cells and neuron loss in hippocampus are related to generalized convulsions in man. Generalized convulsions provoked by electric shock in rats do not result in neuron loss. However, mongolian gerbils from seizure-susceptible strains with "spontaneous" seizures of various types, have a reduced number of H1-neurons and Purkinje cells after only a restricted number of seizures of any type. Loss of neurons is a possible consequence of generalized convulsions. Even "seizure activity", as such, seems to damage nerve cells. The consequence is early effective treatment in such cases where epilepsy is a secondary threat as in febrile convulsions, post-traumatic, post-infectious and post-infarction epilepsy. PMID- 1414263 TI - Clinical classification of dementia conditions. PMID- 1414264 TI - Descriptive epidemiology and risk factors for Alzheimer's disease. PMID- 1414265 TI - Clinical diagnosis of Alzheimer's disease by primary care physicians and specialists. PMID- 1414266 TI - Alzheimer's disease. Diagnosis by specialists: psychological testing. PMID- 1414267 TI - EEG in diagnostics and follow-up of Alzheimer's disease. PMID- 1414268 TI - Functional imaging procedures in dementias: mapping of EEG and evoked potentials. PMID- 1414269 TI - Differential diagnosis of cortical vs subcortical dementing disorders. PMID- 1414270 TI - Biological markers and the cholinergic hypothesis in Alzheimer's disease. PMID- 1414271 TI - Tacrine in Alzheimer's disease. PMID- 1414272 TI - The pathology of dementias: an overview. PMID- 1414273 TI - Alzheimer's disease. Nonpharmacologic treatment of behavioral symptoms. PMID- 1414274 TI - Memory training and memory improvement in Alzheimer's disease: rules and exceptions. PMID- 1414275 TI - Ultrastructure of the microglia that phagocytose amyloid and the microglia that produce beta-amyloid fibrils. AB - The function of microglia associated with beta-amyloid deposits still remains a controversial issue. On the basis of recent ultrastructural data, microglia were postulated to be cells that form amyloid fibrils, not phagocytes that remove amyloid deposits. In this electron microscopic study, we examined the ability of microglia to ingest and digest exogenous amyloid fibrils in vitro. We demonstrate that amyloid fibrils are ingested by cultured microglial cells and collected and stored in phagosomes. The ingested, nondegraded amyloid remains within phagosomes for up to 20 days, suggesting a very limited effectiveness of microglia in degrading beta-amyloid fibrils. On the other hand, we showed that in microglial cells of classical plaques in brain cortex of patients with Alzheimer's disease, amyloid fibrils appear first in altered endoplasmic reticulum and deep infoldings of cell membranes. These differences in intracellular distribution of amyloid fibrils in microglial cells support our observations that microglial cells associated with amyloid plaques are engaged in production of amyloid, but not in phagocytosis. PMID- 1414276 TI - Neuronal uptake of plasma proteins in brain contusions. An immunohistochemical study. AB - Twenty-five cases of cerebral contusions of various age were examined immunohistochemically for neuronal uptake of albumin and fibrinogen. The neurons in the damaged areas were heavily stained in all cases, even in those of only a few minutes' survival, and they remained positive for serum proteins until they disappeared from the lesions. In hematoxylin and eosin-stained sections, neuronal changes were observed from the first minutes after the lesion but they were indistinguishable from the shrunken "dark" neurons that occur as artifacts in poorly fixed material. However, in contrast to the artificially changed cells, the truly damaged ones took up serum proteins. It is concluded that staining with antisera against serum proteins may serve as early markers for neuronal injury before reliable histological changes have developed. PMID- 1414277 TI - Tubulovesicular structures in Creutzfeldt-Jakob disease. AB - By electron microscopy tubulovesicular structures (TVS) have been consistently observed in brain tissue of transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced, but not naturally occurring, Creutzfeldt-Jakob disease (CJD). For the first time we report here the presence of TVS in human brains with CJD as detected by transmission electron microscopy. TVS were observed in all three CJD specimens (two biopsies, one autopsy), but they were rare and were found only in one or two location(s) per grid. TVS were seen in distended pre- and postsynaptic terminals and measured approximately 35 nm in diameter; they were smaller and of higher electron density than synaptic vesicles. Their occurrence in all types of transmissible spongiform encephalopathies irrespective of the affected host and the strain of the infectious agent suggests their biological significance. PMID- 1414278 TI - Immunohistochemical localization of the proteinase inhibitor region of amyloid precursor proteins in the neocortex of Alzheimer's disease and aged controls. AB - The immunohistochemical localization of the proteinase inhibitor region of amyloid protein precursors (APPI) in the postmortem human neocortex was studied using a polyclonal antibody raised against a purified recombinant human APPI derivative produced by COS-1 cells. APPI-like immunoreactivity (APPI-LI) was found diffusely in the human neocortex. APPI-LI appeared as irregularly shaped granular structures. The size of the APPI-LI structures was 1-4 microns in diameter. APPI-LI usually formed a cluster of 10- to 20-microns diameter in the cortical gray matter and 20- to 40-microns diameter in the subcortical white matter. Double staining for APPI and glial fibrillary acidic protein indicated that APPI-LI in the white matter and molecular layer was localized exclusively in the fibrillary astrocytes. In contrast, APPI-LI was found in neurons as well as in the fibrillary astrocytes in layers II through to VI. Under fluorescence microscopy, APPI-LI in both neurons and fibrillary astrocytes were found in close association with lipofuscin. The present observations indicate that APPI is localized in neurons and astrocytes in the human neocortex and that APPI may be associated with lipofuscin or lysosome in the human neocortex. PMID- 1414279 TI - Neuropathologic findings in surgically treated hemimegalencephaly: immunohistochemical, morphometric, and ultrastructural study. AB - Tissues from three cases of hemimegalencephaly (HME) causing intractable seizures treated by cortical resection were studied using immunohistochemical, ultrastructural, and morphometric techniques. Severe cortical dysplasia was seen in all cases and included lesions best characterized as hemilissencephaly and polymicrogyria. Blurring of the cortex-white matter junction, the presence of large neuronal heterotopias, and neuronal cytomegaly were frequent observations. Immunohistochemical analysis demonstrated cellular colocalization of astrocytic markers glial fibrillary acidic protein and vimentin in one case of hemilissencephaly. Morphometric data showed significant increases over controls in neuronal profile area in all cases of HME. Neuronal cell density was increased significantly above controls in one of the cases. The study shows that HME results from severe cortical dysplasia which may be caused by multiple insults, manifest in one of several ways, and reflects abnormal or altered signals that regulate cortical morphogenesis. PMID- 1414280 TI - Stress-response (heat-shock) protein 72 expression in tumors of the central nervous system: an immunohistochemical investigation. AB - This report deals with the expression of stress-response (heat-shock) protein 72 (srp 72) in a series of 95 primary human brain tumors and 21 carcinoma metastases to the central nervous system (CNS). Immunohistochemical procedures were employed; cells of the human cervical cancer line HeLa S3 were used as positive controls. The protein was detected in 14/22 meningiomas and in 6/13 glioblastomas. Tumor cells expressing srp 72 were also found in 4/17 astrocytomas, 2/9 pituitary tumors, 2/14 primitive neuroectodermal tumors and 1/10 medulloblastomas. Whereas the majority (8/10) of the breast carcinoma metastases had tumor cells that expressed srp 72, only 2/11 lung tumor metastases were positively stained. These results document srp 72 expression by a variety of primary and metastatic tumors of the CNS. PMID- 1414281 TI - The cerebrovascular response to experimental lateral head acceleration. AB - A number of microvascular changes, such as the development of astrocyte lucency, increased endothelial pit/vesicle activity, development of crater like lesions, and endothelial microvilli have been reported after injury to the brain. Lateral head acceleration in the non-human primate, however, still provides the best experimental model for human diffuse axonal injury. No attempt has yet been made to document the spatial extent or time course of the microvascular response to acceleration injury to the head. We have examined the brains of baboons 1, 4, 6, and 12 h and 7 days after acceleration injury to the head to analyse the microvascular response. In the experimental animals there was a short-term rise in intracranial pressure followed by a long-term resolution, and a reduction in both mean arterial blood pressure and cerebral perfusion pressure which, however, never dropped below 75% of baseline for more than 5 min after injury in any animal. We found evidence for extravasation of blood in a small number of blood vessels in all parts of the brain. Interendothelial tight junctions are not disrupted. Pit/vesicle activity rises in the 1st h in the occipital cortex, but not until 4 h in the frontal cortex, and remains elevated for at least 7 days. There is little change in the thalamus. Development of microvilli is most rapid in the frontal cortex with peak values at 1 h, but slower in the thalamus and occipital cortex where peak values are only obtained at 6 h. Highest numbers of microvilli occur in parasagittal regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414282 TI - Simultaneous detection of ferritin and HIV-1 in reactive microglia. AB - Using ferritin as a marker of reactive microglia, we demonstrated a close association between proliferation of reactive microglia and expression of human immunodeficiency virus type 1 (HIV-1) in brain tissue from autopsied cases of acquired immunodeficiency syndrome (AIDS). An increased number of ferritin positive reactive microglia was observed in formalin-fixed paraffin-embedded brain sections from all 13 AIDS cases examined. Similar findings were observed in brain tissue from other neurological diseases (subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis). Multinucleated giant cells were found in 7 of the AIDS cases which were also intensely labeled for ferritin. Dual-label immunohistochemistry using anti ferritin and cell-specific markers showed that ferritin-positive cells were distinct from astrocytes, neurons and endothelia using anti-glial fibrillary acidic protein (anti-GFAP), anti-neurofilament protein and Ulex europaeus agglutinin 1, respectively. In 5 AIDS brains, only ferritin-positive cells were shown to contain HIV-1 gp41 antigen using dual-label immunohistochemistry. In addition, HIV-1 RNA was localized in ferritin-positive reactive microglia but not in GFAP-positive astrocytes using immunohistochemistry combined with in situ hybridization. Ferritin-positive reactive microglia and multinucleated giant cells were co-labeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). However, RCA-1 also extensively stained resting microglia only a few of which were co-labeled for ferritin. The density of ferritin-positive cells was correlated with the presence of HIV-1 RNA-positive cells in AIDS brain. Thus, ferritin immunoreactivity can be used as an activation marker of microglia in archival paraffin sections and reflects the extent of inflammation in HIV-1 infected brain. PMID- 1414284 TI - Brain lesions of the Leigh-type distribution associated with a mitochondriopathy of Pearson's syndrome: light and electron microscopic study. AB - Pearson's syndrome is a disease of refractory sideroblastic anemia and exocrine pancreatic dysfunction due to abnormal mitochondrial DNA (mtDNA). A male infant with Pearson's syndrome developed necrosis of both thalami and basal ganglia when he suffered from gastroenteritis at 1 year and 11 months of age. He died of sepsis at the age of 2 years and 4 months. Analysis of mtDNA from various organs revealed abnormal mtDNA with deletion by 5 kbp, confirming the diagnosis. At autopsy, the brain had symmetrical cavities in putamen, caudate nuclei and medial nuclei of the thalami. Ferruginous granules in nerve cells in medial thalamic nuclei, and scattered round bodies with neuronophagia in lateral nuclei were found at light microscopic observation. Electron microscopy showed that these granules were composed of radiating spicules and a dense layer containing packed cytoplasmic organelles, respectively. The macroscopic distribution of brain lesions was very similar to and characteristic of Leigh's disease. This similarity leads to the supposition that defective intracellular energy utilization common to Leigh's disease could be responsible for brain lesions in this case. Although the histological appearance was somewhat atypical for Leigh's disease, very acute formation of brain lesions in this case was thought to have caused the histological difference. PMID- 1414283 TI - Increased iron content in the putamen of patients with striatonigral degeneration. AB - We measured the total content of iron, copper, zinc and manganese in the putamen of four patients with striatonigral degeneration (SND) and age- and gender matched normal controls. The iron content in the SND patients was five times greater than in the controls. Electron microscopic histochemistry revealed the iron reaction products in the pigments showing a triphasic pattern of coarse, electron-dense globules, fine granular and fibrillary materials, and lamellated structures. These findings suggest that increased iron deposition may be related to pigment formation in the putamen of SND. PMID- 1414285 TI - Prevalence of retinitis pigmentosa and allied disorders in Denmark. II. Systemic involvement and age at onset. AB - A population survey of retinitis pigmentosa and allied disorders in the Danish population disclosed 1301 cases prevalent in Denmark per January 1, 1988. Crude prevalence rates and World Standardized prevalences of systemic and non-systemic RP are presented. Sixty-four per cent of all RP-cases were non-systemic. A preponderance of males was encountered in both systemic and non-systemic RP. Usher disease was diagnosed in 12%, Bardet-Biedl syndrome constituted 5%, and the frequency of Spielmeyer-Vogt disease was 1% of all prevalent RP-cases. Other defined syndromes occurred in 1% of the cases. The Danish figures with respect to Usher disease are compared with standardized prevalence rates from Sweden and Finland. Nineteen per cent of patients affected by non-systemic RP had an onset later than 30 years of age. In patients affected by systemic RP the eye disease tended to an earlier debut with only a few per cent beginning after the age of 30 years. PMID- 1414286 TI - Contrast visual acuities in cataract patients. II. After IOL implantation. AB - Contrast visual acuities were measured in 100 eyes of 75 patients who attained a best-corrected visual acuity of greater than or equal to 0.8 (20/25) after intraocular lens (IOL) implantation. The variable contrast visual acuity chart (VCVAC), with three contrast levels of 90, 15, and 2.5% and reverse polarity of 90% contrast, was used to measure contrast visual acuities. The follow-up period ranged from 3 to 35 months (mean 7.41). The mean visual acuities measured with the 90, 15, and 2.5% charts were 0.92 (SD = 0.11), 0.59 (SD = 0.13), and 0.33 (SD = 0.14), respectively. The mean visual acuity measured with the 90% reverse polarity chart was 0.97 (SD = 0.11). The decreases in visual acuities compared with the 90% contrast were 0.64 and 1.48 octaves in the 15% and the 2.5% contrast charts, respectively. The pattern of the contrast acuity profile was comparable to normal subjects, but in 28 of 100 (28%) eyes, the visual acuities measured with the reverse polarity chart were slightly better than those measured with the standard 90% contrast chart, suggesting that the glare effect still exists after IOL implantation, though to a lesser degree than in cataractous eyes. PMID- 1414287 TI - Exfoliation syndrome in patients scheduled for cataract surgery. AB - A series of 305 consecutive patients 30 years of age or older scheduled for cataract surgery was examined to find out the frequency of exfoliation syndrome, the predominant type of cataract, and the intraocular pressure status. The mean age of 222 (72.8%) females and 83 (27.2%) males was 71.7 (+/- 11.1) years (range 32 to 91 years). Exfoliation was detected in 77 (25.2%) patients. It was unilateral in 37 (48.0%) patients, the affected eye being in 29 (78.4%) cases scheduled for cataract surgery, and bilateral in 40 (52.0%) patients. Exfoliation was increased steadily with age. It was most often seen on the anterior lens capsule (88.9%). Krukenberg's spindle was seen in 31 (20.4%) eyes of patients with and in 12 (2.6%) eyes of patients without exfoliation (p less than 0.001). Nuclear sclerosis predominated in eyes with (83.8%) as compared to those without (61.9%) exfoliation (p less than 0.01). Posterior subcapsular cataract was less common in eyes with exfoliation (1.5%) than in eyes (21.1%) without it (p less than 0.001). A tendency to slightly higher preoperative intraocular pressure was measured in eyes with exfoliation as compared to those without it, and glaucoma occurred much more frequently (33.8% vs 10.8%) in the former group (p less than 0.001). Exfoliation and capsular glaucoma, which must be promptly detected to avoid surgical complications, are frequent in patients scheduled for cataract surgery. PMID- 1414288 TI - Fluorescein and fluorescein glucuronide in plasma. AB - The evaluation of the blood-ocular barrier for fluorescein requires the measurement of free and unconjugated fluorescein in plasma. This study introduces a new and simple method for the determination of free fluorescein in plasma on the basis of determined total free plasma fluorescence and the free fraction of fluorescence. An excellent good correlation between differential spectrofluorophotometry and this new method is demonstrated. After intravenous administration of sodium fluorescein, the contribution of fluorescein glucuronide to total free plasma fluorescence was evaluated on basis of the areas under the plasma concentration/time curves for fluorescein and fluorescein glucuronide, respectively. After 1 h 8.2% of total free fluorescence in plasma was found to originate from fluorescein glucuronide and after 24 h 18.3% originated from this metabolite. It was concluded that although plasma fluorescein glucuronide measurements are important in the exact evaluation of the blood-ocular barrier, the contribution of fluorescein glucuronide to vitreous fluorescence after intravenous fluorescein administration seems to be of minor magnitude. PMID- 1414289 TI - Primary argon laser trabeculoplasty vs. pilocarpine. Short-term effects. AB - This is a prospective study of 82 newly discovered patients with simplex or capsular glaucoma from two centres, collected between 1984 and 1989 and selected at random for primary treatment by either laser or pilocarpine. Preliminary two year follow-up shows that primary laser treatment gives a significantly higher number of patients where the intraocular pressure is successfully controlled. Primary argon laser trabeculoplasty has been carried out in 40 patients. The first treatment was given to either the upper or to the lower half of the trabecular meshwork. In the second treatment after one month the other half was treated. In both groups the first treatment gave the highest pressure reduction. The somewhat higher pressure reduction after upper treatment versus lower was insignificant. The degree of trabecular pigmentation did not influence the two month follow-up result, neither did the type of glaucoma. Of the eyes treated with laser, peripheral anterior synechiae could be seen in 18%. Acute intraocular pressure rises greater than 5 mmHg occurred in 21% of the eyes after the first treatment and in 37% after the second treatment. Pressure rises greater than 10 mmHg occurred in 5% after the first and in 10% after the second treatment. No pressure-lowering substances were given. Considering that 16% of the eyes had an intraocular pressure that was higher than baseline pressure even 6 h after either first or second treatment, it is recommended that a pressure-lowering medication on the day of treatment should be administered. PMID- 1414291 TI - Quantitative layer-by-layer perimetry adapted to the Humphrey Field Analyzer. I. Design of methodology and instrumentation. AB - Quantitative layer-by-layer perimetry is a psychophysical technique believed to assess response characteristics of individual retinal layers. This paper presents a new design of this technique, implemented into the existing hardware environment of the computerized perimeter Humphrey Field Analyzer. The technique was optimized for a more simple, fast and reproducible testing of larger visual field point patterns. The paper deals with the design of instrumentation and with methodological aspects of this adaptation of the technique. PMID- 1414290 TI - Epikeratophakia for keratoconus. Long-term results using fresh, free-hand made lamellar grafts. AB - Epikeratophakia using fresh, free-hand made corneal grafts was done in 16 patients with keratoconus. The follow-up period averaged 27.8 months (range 13-45 months). A significant improvement of visual acuity was obtained (p = 0.002), and 14 of the 16 eyes (87.5%) achieved a corrected visual acuity greater than or equal to 6/12. The spherical equivalent and the cylindrical refractive error were reduced (p less than 0.05), and a significant flattening of the central corneal curvature was obtained (p less than 0.002). The mean postoperative central corneal astigmatism was 4.25 D. Postoperatively, the mean central corneal thickness was 0.670 mm, and the mean central thickness of the epithelialized graft was 0.336 mm. Six patients reported some postoperative glare or blurring of vision, despite a visual acuity greater than or equal to 6/9 on the Snellen chart. No significant subjective or objective changes were noticed after the 6 month postoperative follow-up visit. PMID- 1414292 TI - Quantitative layer-by-layer perimetry adapted to the Humphrey Field Analyzer. II. Centre-surround interaction produced by sustained surround stimulation. AB - In this paper the practical applicability of a new design of quantitative layer by-layer perimetry is confirmed by studying centre-surround interaction produced by sustained surround stimulation in preliminary trials on four normal individuals. The results are discussed in relation to established laws for retinal light perception, and some practical aspects of the employed test design and the chosen test variables are discussed. PMID- 1414293 TI - Quantitative layer-by-layer perimetry adapted to the Humphrey Field Analyzer. III. Centre-surround interaction produced by transient surround stimulation. Area characteristics of the transient stimulus pattern. AB - In this paper some qualitative aspects of centre-surround interaction produced by transient surround stimulation are investigated, employing a new design of quantitative layer-by-layer perimetry. Using a rotating windmill pattern, a transient response, believed to be organized in the inner plexiform layer of the retina, is assessed in four normal individuals. The paper considers area characteristics of the stimulus pattern used to produce the transient response, and optimal dimensions for this pattern are proposed. PMID- 1414294 TI - The cumulative frequency distribution curve of the eye pressure. AB - Knowledge of the probability of having glaucoma at different levels of eye pressure is a prerequisite for estimating at which eye pressure levels preventive pressure-lowering treatment ought to be applied. The glaucoma tolerance may not be the same in all population groups. Calculation of tolerance distribution curves may be performed if the frequency distribution curves of pressure in eyes with and without glaucoma are known. Regression analysis has been performed to compute curves approaching the cumulative frequency distribution of the eye pressure in different subgroups. Results of a population study including subjects greater than or equal to 65 years of age have been used. An equation describing an asymmetric sigmoid curve has been applied in the curve fitting procedure. The derivative of this equation was used to describe the noncumulative frequency distribution curves. The analysis has been performed in subgroups consisting of normal eyes, glaucomatous eyes, eyes with and without pseudo-exfoliation. PMID- 1414295 TI - Long-term study of patients with congenital pit of the optic nerve and persistent macular detachment. AB - During the period 1970-87 we evaluated the changes of the optic disc, peripapillary area, detached macula and visual acuity in 16 cases with congenital pit of the optic nerve and macular detachment. The study revealed in 9 of the 16 cases (56%) an increase of the dimension of the pit or changes in its color, findings which were directly related to the duration of the macular detachment. Chorioretinal scarring, pigment migration, or both, were also noted mainly at the temporal margin of optic disc. In 5/16 cases we found during the follow-up an extension of macular elevation. In altogether 10 out of 16 cases the retinal elevation covered the larger portion of the mid-periphery temporally. In 7/16 cases the final visual acuity remained unchanged, in 9/16 cases deteriorated. The difference, however, in the latter 9 cases between initial and final visual acuity was negligible. During the follow-up period deterioration of the visual fields was also noted. PMID- 1414296 TI - Polyamine and histopathological changes after unilateral endotoxin-induced uveitis and its contralateral effects. AB - The polyamines putrescine, spermidine and spermine are essential for normal cell function and proposed to be involved in inflammatory reactions. The polyamines were measured bilaterally in rabbit aqueous humor after unilateral endotoxin induced uveitis. The contralateral eyes were injected with saline or not touched. Aqueous protein levels and leukocytes were determined and a histological evaluation was performed. Protein, leukocytes, putrescine and spermine increased in the treated eyes, but not in the untouched eyes. When saline was injected in the contralateral eye, a small increase in spermine was seen. Spermidine decreased first, but increased later, in both the endotoxin-injected and the other eye. Histopathologically, the treated eyes showed an infiltration of leukocytes, vasodilatation and in some cases optic nerve involvements. A mild reaction was also seen in the unchallenged contralateral eyes. The results show that polyamines might serve as a marker for acute inflammation in the eye and that the mechanism of putrescine and spermine induction is different from the one of spermidine. Polyamines are suggested to play a role in the cellular immune response. PMID- 1414297 TI - Serum alpha-1 acid glycoprotein levels in patients with idiopathic peripheral retinal vasculitis (Eales' disease). AB - Serum alpha-1 acid glycoprotein levels were measured in 27 patients with idiopathic peripheral retinal vasculitis (Eales' disease) and 31 healthy subjects by single radial immunodiffusion technique. The levels were found to be significantly increased in both moderate and severe types of the disease. The serum levels of this protein paralleled the severity of the disease. The increased alpha-1 acid glycoprotein in serum showed a significant fall to near normal levels during the quiescent stage. Our observations support the hypothesis that idiopathic peripheral retinal vasculitis is an immune mediated disease. It is proposed that serum alpha-1 acid glycoprotein may be considered as a reliable parameter of the activity and the degree of severity of the disease, as well as an useful tool for monitoring the efficacy of treatment. PMID- 1414298 TI - Sucralfate and sodium sucrose sulphate in the treatment of superficial corneal disease in keratoconjunctivitis sicca. AB - We have studied the effect of the aluminum complex of sucrose sulphate (Sucralfate suspension) and the sodium salt of sucrose sulphate (sodium sucrose sulphate solution) on patients with keratoconjunctivitis sicca. Eyes treated with either of these two drugs showed a decrease in painfulness and blurring of vision. On examination the surface area of the corneal lesions, stained with fluorescein, diminished during treatment. As for the difference in effect between the two eyedrops, the solution was better tolerated. PMID- 1414299 TI - The effect of indomethacin 1% ophthalmic suspension on the pupil during extracapsular cataract surgery. AB - Fifty-six patients who underwent extracapsular cataract surgery were randomized in two groups with 28 patients in each group. Group 1 was treated with standard preoperative dilation regime and group 2 received in addition indomethacin 1% ophthalmic solution. Horizontal and vertical pupil diameter measurements were taken before capsulotomy, before exprimation of the lens nucleus and before lens implantation. The size of the pupil at the time of capsulotomy and at the time just before lens exprimation was greatest in the non-indomethacin treated group, but at the time of lens implantation the pupil of the indomethacin treated group was greatest. It is concluded that even though indomethacin seems to be able to inhibit surgically induced miosis, probably through its inhibitory effect on prostaglandin synthesis, the effect is only marginal and from a clinical point of view it cannot be recommended. PMID- 1414300 TI - Serum transferrin in patients with retinitis pigmentosa. AB - The CDG syndrome is a newly detected disorder with a carbohydrate defect in glycoproteins such as transferrin. As retinitis pigmentosa is a part of this syndrome, there could also be other subtypes of retinitis pigmentosa with a similar biochemical defect. Isoforms of serum transferrin were therefore analysed in 78 patients from different families with retinitis pigmentosa and showed slightly or moderately elevated values for less glycosylated isoforms in two families. The study suggests that abnormal glycoprotein metabolism manifested by elevated values of carbohydrate-deficient isotransferrins may be present in a small proportion of families with retinitis pigmentosa. The relationship between the glycoprotein defect and retinitis pigmentosa remains to be established. PMID- 1414301 TI - Fluconazole in the treatment of candida albicans endophthalmitis. AB - A 29-year-old former drug addict with candida albicans endophthalmitis determined by cultivation was treated with vitrectomy and systemic fluconazole. The infection resolved completely and the patient recovered a visual acuity of 6/6. Fluconazole was well tolerated and a high concentration was found in the vitreous cavity. PMID- 1414302 TI - Excimer laser treatment of pterygium. AB - Primary experience with the use of excimer laser in pterygium therapy is presented. Twenty-two pterygia (11 primary and 11 recurrent) were surgically removed using the bare-sclera technique followed by excimer laser ablation to smooth the corneal surface. As recurrence was observed in 20 eyes (91%) during the first year, supplementary excimer laser treatment of a pterygium does not seem to reduce the recurrence rate. The high recurrence rate in this series may to a certain extent reflect the surgical technique used (bare-sclera). PMID- 1414303 TI - Asymmetry of retinitis pigmentosa-related to initial optic disc vasculitis. AB - A case of highly asymmetric retinitis pigmentosa is reported. Signs of pigmentary retinopathy appeared in the first eye following optic disc vasculitis or neuroretinitis of unknown etiology. Within 2 years the visual field became markedly restricted and the dark adaptation thresholds elevated. Twelve years later this eye was almost blind and the ERG was non-recordable. In the fellow eye, the first pigmentary changes were observed 5 years after the initial presentation, and the progression was slow. Nineteen years after the initial examination the visual field of the less affected eye was constricted to 30 degrees nasally and 60 degrees temporally, the dark adaptation threshold was only slightly elevated, and the full-field ERG was within normal range. It is possible that neuroretinitis or vasculitis of the optic disc caused the earlier onset and the more progressive course of pigmentary retinopathy in the initially affected eye. PMID- 1414304 TI - Spontaneous resolution of proliferative vitreoretinopathy. AB - A case of proliferative vitreoretinopathy that spontaneously regressed, leading to reattachment of the retina, is presented. The importance of such a spontaneous resolution in terms of understanding the pathogenesis, and planning a treatment, is discussed. PMID- 1414305 TI - [Historical notes on the ethmoid bone]. AB - The intriguing historical exploration of the anatomy of the ethmoid and ethmoidal cells is described. Despite continuing research, the ethmoid remains a puzzling topic. PMID- 1414306 TI - [Surgical anatomy of the middle meatus and ethmoid]. AB - The evolution of rhino-sinusal endoscopy and the progress in endonasal surgery under endoscopic guidance, justifies a review of the ethmoid anatomy. A simple and logical scheme of the ethmoid bone is presented. The observer has to develop an "endoscopic eye" since the panoramic view offered by the optics modifies the image. Special attention is drawn upon the endoscopic anatomical fine points in the crucial area of the "bullar circus". These are necessary guides in surgical practice. PMID- 1414307 TI - Nasal septum deviation in newborns. AB - The patency of the nose is very important for the newborn. Nasal septum deviation (NSD) is one of the most important factors causing disorders of the patency of the nose. It is usually the result of mechanical trauma. The relationship between the course of delivery and deformation, deviation and luxation of the nasal septum is examined. 410 newborns--297 born in natural labour and 113 in Caesarean section, were examined. Also the kind of birth, the position of the fetus during the first and second stages of labour and the weight of the newborns was analyzed. NSD was found in 14.3% of the cases. Follow-up examination of those children was performed 4-6 months after the first check-up. NSD was observed mainly in children born head first. PMID- 1414308 TI - [Endonasal microsurgery of antro-choanal polyps]. AB - Between 1986 and 1991, 33 patients were operated on by the senior author. Neither sex, nor side prevalence has been observed. In 50% of the cases, the patient was a teenager. In 18% of the cases, a cystic oedematous transformation was the cause of the polyp. Its treatment must be surgical. Five cases were operated on by gingival access, the others by median and inferior meatotomy which is recommended by the authors. They found one recurrence out of the recorded 24 cases. PMID- 1414309 TI - [Medial maxillectomy in transitional papilloma]. AB - Transitional Papilloma, the formerly inverted papilloma, is a rather rare neoplasm of the nasal cavity. Its origin is still debated. The only constant symptom is unilateral nose obstruction. This lesion is of considerable interest because of the recurrence tendency and its association with malignancy. Although a benign tumor, radical aggressive surgery is advocated. A medial maxillectomy is the treatment of choice. A sublabial incision gives excellent exposure without external facial scar. PMID- 1414310 TI - [Medico-surgical management of chronic maxillary sinusitis in adults]. AB - Every maxillary sinusitis suspected of chronicity has to be fully investigated by CT-scan. Failure of medical treatment will confirm chronic disease and will lead to surgery. According to the authors, endoscopic middle meatotomy is the treatment of choice, possibly associated with anterior ethmoidectomy and/or inferior meatotomy. PMID- 1414311 TI - [Sinus mucoceles: diagnostic and surgical aspects (apropos of 8 cases treated with rhino-surgical endoscopy)]. AB - Sinus mucoceles are benign and expansive pseudocystic formations situated in the paranasal sinuses. Their pathogenicity is still misunderstood. Clinical signs are multiple and often delayed due to tumour localisation. CT-scan is the best diagnostical investigation and surgery the treatment of choice. Marsupialization under endoscopic control is becoming widespread. PMID- 1414312 TI - [Orbital involvement of sinusitis]. AB - Sinusitis can spread to the orbital tissues. 'Preseptal' soft-tissue bacterial infections are relatively common during childhood and with appropriate antimicrobial therapy they usually resolve quickly. 'Orbital' soft-tissue infections, in contrast, are relatively rare and frequently cause serious morbidity. Four cases are presented. Symptomatology and pathogenesis are reviewed. Diagnostic procedures, especially CT-scan, are discussed and recommendations are given for medical and surgical management. PMID- 1414313 TI - Dysthyroid orbitopathy and orbital decompression. A review. AB - In the treatment of severe manifestations of dysthyroid orbitopathy, such as optic neuropathy and exposure keratitis, orbital decompression occasionally may be performed if steroids fail. In general, medial and inferior orbital wall decompression gives satisfactory results. The route may be transantral, but the transconjunctival or endonasal approach may be more appropriate for extraocular muscle balance and optic neuropathy respectively. PMID- 1414314 TI - Optic nerve decompression for indirect posterior optic nerve trauma. AB - Posterior indirect optic nerve trauma is a rare but possibly dramatic event. Since spontaneous recovery is unlikely, medical treatment by megadose steroid therapy is advocated. Optic nerve decompression may be usefull, but is still controversial. Medial optic canal wall decompression seems best and may be achieved by various approaches. PMID- 1414315 TI - [Anterior sinusitis: indications for and results of endoscopic surgery]. AB - With the exclusion of posterior or diffuse disease, anterior sinusitis is an inflammatory process affecting one or more cells draining through the middle meatus. When medical treatment fails, functional endoscopic surgery is indicated. Two hundred and three surgical cases are reviewed. Anterior sinusitis forms 44% of the surgical indications. Twenty months later, 80% obtain good or very good subjective and objective results. In 20% the quality is poor with suppuration. When suppuration persists, further endoscopic or radical surgery is indicated. In this series, complication rate is low. Endoscopic surgery advantages are discussed. PMID- 1414316 TI - [Preoperative radiotherapy and medial maxillectomy. Treatment concept for carcinomas of the nasal cavity and paranasal sinuses]. AB - Multimodal treatment modality for paranasal sinus malignancies is discussed. Therapy consists in pre-operative 50 Gy radiotherapy delivered over 5 weeks, followed three weeks later by a medial maxillectomy. Although local control rate is improved through this treatment, an increase in late metastases is observed. PMID- 1414317 TI - [Techniques of uvulopharyngoplasty for snoring]. AB - Snoring is considered abnormal even in children. Breathing difficulties can modify the development of the face and provoke upper respiratory dysfunction. Some surgical techniques are presented. PMID- 1414318 TI - [Medicolegal implications of sinus surgery]. AB - Possible sinus surgery complications are reviewed. The difficult anatomy and its relationship with the orbit, the optic nerve and the olfactory fossa are the main reason of complication. However by technical improvement of imaging and endoscopy, as well as by surgical skill refinement the complication rate decreases. In the patient's interest, and to avoid medico-legal suits, some recommendations are suggested. PMID- 1414319 TI - [The cervicofacial manifestations of Kaposi's sarcoma and of non-Hodgkin's lymphomas in HIV-infected patients]. AB - Infection from human immunodeficiency virus (HIV) is well known for the particular host susceptibility to a variety of opportunistic infections and unusual malignant neoplasms. Although no tumor develops exclusively in concomitance with HIV infection, malignancies in these patients have different clinical behaviour, response to treatment and prognosis than the pattern observed in HIV negative hosts. Kaposi's sarcoma (EKS) and non-Hodgkin's lymphoma (NHL) are tumors per se diagnostic of AIDS in patients with HIV infection. From 1987 to 1991, 210 HIV positive patients underwent ENT examination without symptom-related selection: 128 were intravenous drug users, 50 homosexual males, 22 heterosexuals, 4 intravenous male homosexual drug users, 3 blood recipients and 3 subjects without known risk factors. Sixteen were allocated in group II, 37 in III, 9 in IV A, 2 in IV B, 31 in IV C1, 37 in IV C2, 48 in IV D and 30 in IV E. Fourteen had head and neck EKS localization. All were males, with a median age of 40 of which 11/14 were homosexuals. The concomitant involvement of skin and mucosa was the most common manifestation and the palate was the most frequently affected mucosal site. Twenty-four had NHL localized within the head and neck: 21 males and 4 females with a average age of 38, 10 intravenous drug users, 9 homosexual males, 3 heterosexuals, 1 blood recipient, 1 subject without known risk factors. Extranodal localization was the most frequent characteristic while the gums were the most commonly involved site. The main characteristics of head and neck manifestations of EKS and NHL are reported with references to literature. The majority of HIV infected patients with EKS or NHL have ENT localizations, perhaps because lymphatic tissue, a HIV target, is well represented in this area and contamination by infectious agents (such as Epstein Barr virus and cytomegalovirus, probably involved in the pathogenesis of EKS and NHL) can easily occur in the head and neck. The otolaryngologist should be aware of the various, and sometimes misleading, characteristics of these diseases. PMID- 1414320 TI - [The reliability of biopsy-determined grading in laryngeal squamous cell carcinoma]. AB - Grading evaluation is becoming increasingly more important in establishing a valid prognosis and in the choice of therapeutical strategies in dealing with squamous laryngeal cancer. It follows, therefore, that grading of bioptic tissue, made before therapy planning, must offer reliable data and correspond to data gathered through grading of the entire neoplasm. Thus the aim of our study carried out on 267 cases was to verify if grading of bioptic tissue corresponds to that of the operatory specimen. In 7% of the cases (19 in 267) bioptic grading overestimated the neoplasm in that post-operatory grading revealed a less differentiated form. On the contrary, in 16% of the cases (43 in 267) bioptic grading underestimated the form since as post-operatory grading showed a more highly differentiated form. It appears clear that these values depend on the clinical extension of the neoplasm in that the difference was inferior in the case of limited neoplasms and greater in that more largely extended ones. Generally speaking then, the less extended the neoplasm (the most frequently observed clinical form), the more coinciding the bioptic evaluation indicating good differentiation with the post-operatory evaluation. On the other hand, bioptic evaluation indicating moderate or poor differentiation is less reliable since it does not coincide with findings in approximately 16% of the neoplasms, above all those most limited (12%). This means that any reductive adoption of therapy planning made on the basis of the degree of differentiation revealed upon bioptic examination is possible only in the case of those forms more advanced with regard to extension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414321 TI - [Local immunity following treatment with S-carboxymethylcysteine-lysine in tracheotomy patients]. AB - Pathological modification in secretory IgA values as well as in circadian rhythms were found in tracheotomized patients in both nasal and tracheo-bronchial secretions. The protective role of the mucosal immune system in addition to the frequency of severe infectious respiratory diseases in laryngectomized patients justifies the efforts of clinicians to prevent and treat such modifications. Mucoregulatory drugs have a peculiar role in these therapeutical attempts. Forty tracheotomized subjects with neoplastic disease were studied. Twenty received SCMC-Lys as a mucoregulatory drug. IgA 7S, 11S and albumin values in nasal and tracheo-bronchial secretions, were evaluated at surgery, 15 and then 40 days later. In accordance with clinical data, an improvement in local antibody production, damaged by tracheostomy, was found in the treated group. The influence of SCMS-Lys on SIgA production, whose evaluation was made by means of an original, highly selective and sensitive Immuno-IsoElectroFocusing procedure, seems to encourage the use of mucoregulatory drugs in laryngectomized patients. PMID- 1414322 TI - [The incidence and location of inflammatory paranasal sinus lesions in CT]. AB - Several recent studies have labelled the anterior ethmoid as the main source of chronic and/or recurrent sinusitis in the entire paranasal sinus system. In an attempt to identify other possible patterns of developing sinusitis, 1,345 computed tomographies of neurological and neurosurgical patients with no previous history of paranasal sinusitis were evaluated. These scans were made between 1985 and 1989 in the Neurosurgical Clinic of the University of Freiburg. Seventy-five of these studies revealed evidence of inflammatory changes. In 57 scans maxillary sinus disease was evident, while in 46 there was en ethmoid disease, in 24 a sphenoid sinus disease and in 17 a frontal sinus disease. Nine scans showed pansinusitis. In 24 studies, one sinus location was involved (uni- or bilaterally) and among these were 21 with maxillary, 2 with anterior ethmoidal and 1 with frontal sinus involvement. In 38.7% of the examined scans, the anterior ethmoidal complex was free of disease. This study shows that, at least radiographically, the ethmoidal infundibulum is not always the origin of paranasal sinus disease. An isolated frontal, maxillary or sphenoidal sinusitis can develop as well. These results show that a simple anterior ethmoidectomy cannot be considered the panacea for chronic and/or recurring sinusitis. Surgical therapy of inflammatory sinus disease should, on the contrary, be tailored to each patient depending on anamnesis, clinical findings and CT results. PMID- 1414323 TI - [The variability of functional gain and insertion gain in hearing aid fitting]. AB - Functional gain (FG) and insertion gain (IG) are currently used as real ear gain measurement of hearing aids. The gain differences observed with hearing aid modifications made in order to achieve the desired prescriptive target must be greater than the variability associated with repetition of measurement in order to be really useful. Limited research is available on FG and IG intratester variability. In order to evaluate single variability factors, some studies use experimental designs not common in clinical work-up while others use equipment mot available commercially. The present study evaluates intratester variability of FG and IG (Madsen IGO 1500 equipment) in a typical clinical configuration in 42 users of behind-ear hearing aids. Mean standard deviation of FG test-retest differences was 5.19 dB. Range of variability was expressed in term of centiles. 5-- and 95-- centiles were -9.8 and 8.7 dB respectively. Mean s.d. of IG test retest differences was 3.18 dB; 5-- and 95-- centiles were -5.2 and 6.05 dB respectively. Major variability was found at higher frequencies. High variability at lower frequencies was also found probably due to sealing problems of ear molds in the ear canal. Accord between FG and IG was also examined. A good mean correspondence in mid frequency range was found (FG-IG mean difference less than 5 dB) with large inter-subject differences between the two measurements (s.d. 11 dB). PMID- 1414324 TI - [Sandwich-graft myringoplasty: the authors' personal technic and results]. AB - The authors describe the anatomic and functional results obtained with a sandwich myringoplasty technique (MPL) employing an endaural approach. The suggested technique is a modified sandwich MPL by endaural approach with a reduced Shambaugh incision, a systematic profiling of the canal wall bulge and separation of the meatal and tympano-meatal flaps that are maintained pedunculated. The temporal fascia is inserted between the fibrous layer of the tympanic remnant and a single pedunculated tympano-meatal cutaneous flap replaced in the original location. The authors present 72 cases operated between January 1987 and December 1989 for perforations involving up to three quadrants. In 93.1% of the cases a complete and lasting resolution of the perforation was obtained. Of the 5 failures, 4 presented a perforation smaller than the original one. An average (250, 500, 1000 Hz) functional recovery of 14.1 dB was observed compared to an average pre-operatory gap of 21.6 dB. In 25% of the cases, average recovery was greater than 25 dB and in 5 patients a slight worsening with an average difference of -3.3 dB was observed. On the whole, in 41 patients a residual post operatory gap of only 10 dB was achieved. The anatomical results obtained with the MPL presented are similar to those found in the literature describing the classical overlay technique. However, the cases reported do not present those inconveniences associated to the latter technique (lateralization of the graft and blunting). The anatomic and functional results obtained with the technique discussed are on the whole superior to those described with the underlay and the classical overlay techniques. The Authors believe that this is mainly due to the absence of the gelfoam in the middle ear and to the double contention and vascularization of the temporal fascia graft. By means of the profiling of the canal wall the endaural approach permits a good view of the operating field. Furthermore, it is less traumatic and more acceptable to the patient than the postauricular one that has to be limited to the MPL where there are clinical indications for the exploration of antrum. The personal technique here presented implies, however, a certain presence of epithelial pearls. Their localization is nevertheless facilitated by the absence of blunting, thickening and lateralization of the graft. This allows for an early and easy removal on an out patient basis. Other inconveniences of the technique are the length of the procedure and a more difficult control of the ossicular chain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1414325 TI - [Wallenberg's syndrome: an assessment of the dysphagic and postural symptomatology]. AB - Dysphagia and postural disorders are the most important symptoms of the Wallenberg [correction of Wallemberg] syndrome, which takes in a considerable number of neurological symptoms including an alternate sensitive syndrome, the Claude Bernard Horner syndrome, paralysis of the half palate, of the half pharynx and of the vocal fold on the side of the injury, a vestibular syndrome and, finally, a cerebellar hemisyndrome. In the course of this study, four patients with the Wallenberg [correction of Wallemberg] syndrome were examined and underwent further periodical checks after injury. All the patients were fed employing a naso-gastric tube and in one case an emergency tracheostomy was performed because acute dyspnea. The diagnostic protocol following included the collection of a series of anamnestic data, an objective study of U.A.D.T. with fiberoptic endoscopy, swallowing simulation, dynamic radiologic examination (videofluoroscopy) and computerized static posturography. This routine was repeated upon every successive check. During the first observation a substantial uniformity of physiopathological characteristics was found in all the patients. Following logopedic and rehabilitation treatment, a high degree of diversity in the results obtained was observed in three patients (one of the patients was absent from successive checks). The most interesting phenomenon was the difference in time necessary to rehabilitate the swallowing reflex only after which it was possible to reassume oral alimentation. After two months of physiokinesitherapy, computerized static posturography, which initially revealed a sharp increase in the number of oscillations, showed a partial improvement of the postural disease with a reduction in oscillation amplitude. Even though the number of case followed was limited, our experience encourages us to underline importance of immediate rehabilitation therapy and of the collaboration of patients and their family members. PMID- 1414326 TI - [Mycosis of the paranasal sinuses: a report of 4 cases]. AB - With recent advances in medicine, fungal diseases are not only being better under stood, but are also becoming increasingly important in the management of patients with paranasal sinus disease. Fungal sinus diseases range from allergic fungal sinusitis to invasive and fulminant fungal sinusitis. Although patients often have some predisposing factor, such as local tissue hypoxia or massive fungal ++exposure, most patients are not immuno-compromised. Invasive fungal sinusitis may be treated with the traditional Caldwell-Luc surgical technique or with newer endoscopic procedures. Fulminant fungal sinusitis generally occurs in immuno suppressed patients and requires aggressive surgical excision and debridement as well as systemic chemotherapy, usually amphotericin B. In this article we review fungal diseases of the paranasal sinuses and present four cases of paranasal fungal sinusitis. PMID- 1414327 TI - [Histomorphological changes induced by recurrent tonsillitis]. AB - Palatine tonsils are lymphoepithelial mucosal structures whose particular role as a defense mechanism in the human immune system makes them fundamental in protecting organs of much greater importance. If follows, therefore, that dealing with recurrent tonsillar phlogosis--diagnosis as well as therapy choice, surgical or medical--is today problematic and shrouded in doubt. The authors examined tonsillar tissue specimens of 65 patients (age range 4-30 years) who had previously undergone tonsillectomy. Light microscopy and immunocytochemistry were used to study subepithelial tissue while scanning electronic microscope was employed to observe epithelial ultrastructure in order to determine which alterations were most meaningfully correlated to the history and clinical picture of the subjects. In 100% of the cases the cryptic reticular epithelium was hyperplastic while in 44% a squamous metaplasia was observed. Epithelial alteration in various forms was also revealed with scanning electronic microscope: cellular disjunction ridging of the cryptic floor, conrifying squamous epithelial cells, plasma cells and infiltrated lymphocytes. The authors suggest that it is precisely epithelial alteration which, due to inadequate antigen uptake, triggers the series of events which leads from tonsillar disorders to systemic metafocal manifestation. PMID- 1414328 TI - Comparison of the incidence of intracranial hemorrhage following conventional mechanical ventilation and high frequency oscillation in beagle puppies. AB - Controversy exists as to whether high frequency oscillation (HFO) increases the risk of intraventricular hemorrhage (IVH) compared with conventional mechanical ventilation (CMV). We compared the risk of intracranial hemorrhage after phenylephrine-induced hypertension, combined with a hypovolemic, hypotensive insult followed by rapid volume replacement in two groups of newborn beagle puppies (one group on a piston pump HFO and the other on CMV). A total of 12 beagle puppies (6 on HFO and 6 on CMV) survived the protocol. Arterial blood gas analysis and arterial blood pressures through the study were of the same magnitude in both groups. The length of time for which the puppies remained hypertensive and hypotensive also did not vary significantly between the groups. Intraventricular hemorrhages were observed in two of six CMV puppies and two of six HFO puppies. One animal in each group had a white matter hemorrhage. Subarachnoid hemorrhages were seen in 4 animals on CMV and 3 on HFO. This study indicated that HFO does not increase the risk of any kind of intracranial hemorrhage, including IVH, in beagle puppies. PMID- 1414329 TI - Comparison of severity of viremia and antibody responses between infants and children with measles. AB - Severity of viremia and neutralizing antibody responses were compared between nine young infants (less than or equal to 10 months) with measles and 18 infants and children (greater than or equal to 11 months) with ordinary measles. Peripheral blood mononuclear cell (PBMC)-associated viremia was detected between the first day of elevation of fever (day 0) and day 5 of the disease in the former group, whereas PBMC-associated and cell-free viremia were detected between day 0 and day 14 in the latter group. The number of infected PBMC during the first 7 days of the disease was 3.22 +/- 1.07 (log10, mean +/- s.d.) per 10 million PBMC in the former group, which was significantly smaller (P = 0.02) than that of the latter group (4.21 +/- 1.18). The former group reached the maximum level of antibody earlier than the latter group. PMID- 1414330 TI - Neuroradiological findings in glutaric aciduria type I: report of four Japanese patients. AB - We examined neuroradiological computerized tomography (CT) findings and the clinical course of four Japanese children with glutaric aciduria type I (GA1) whose enzyme activity of glutaryl-CoA dehydrogenase was undetectable. Brain CT in all cases examined showed low density white matter, fluid collection in bilateral frontotemporal regions (particularly surrounding the Sylvian fissures), enlargement of the lateral ventricles and slight atrophy of the basal ganglia. Although these findings seemed to be characteristic for GA1, they were unlikely to be more extended, at least over 2 years after infancy. The low density white matter was observed more evidently in the neonatal or early infantile periods than in later periods. The degree of enlargement of fissures in bilateral frontotemporal regions about the Sylvian fissures appeared to correlate with the severity of symptoms such as dystonia or choreoathetosis. Magnetic resonance images (MRI) in one case showed bilateral linear-shaped low intensity in areas of the external capsules and putamen on a T1-weighted image. These CT and MRI findings, as well as clinical symptoms such as choreoathetosis or dystonia, may suggest that metabolic abnormalities in GA1, such as glutaconate, are toxic to the extrapyramidal tract system in the central nervous system, and that the clinical symptoms of the patients are attributable to atrophy of basal ganglia. Brain CT may be useful in diagnosis and evaluation of the clinical course of GA1 patients. PMID- 1414331 TI - Partial imitation and partial sensory agnosia in mentally normal children with convulsive disorders. AB - Mentally normal 6-9 year old children with or without convulsive disorders were examined using the procedures of the five soft signs (SS) selected from conventional soft neurological signs and Berges' gesture imitation tasks. In comparisons of SS between the 60 children with convulsive disorders (CD group) and the 38 without (N group), the average number of SS detected in each case and the incidence ratio of the two signs--partial imitation (PI) and partial sensory agnosia (PSA)--were higher in the CD group than the N group. Examinations of relationships between age, IQ, error index (EI; an index taken from the Continuous Performance Test) and SS, and of correlations among the SS, found two kinds of SS: age-related and El-related signs. The former included right-left confusion, clumsiness and PI, which correlated with each other, while the latter included unstableness of lateral gazing and PSA, which did not correlate with each other. Even though several factors belonging to characteristics of convulsive disorders were evaluated concerning the presence or absence of PI and PSA, there was only one relationship: PSA was more common in children with febrile convulsions than in those with epilepsy. We speculated that PSA reflected an immaturity of the brain in children with febrile convulsions. PMID- 1414332 TI - Oscillatory variations of cutaneous blood flow in newborns using a laser Doppler flowmeter. AB - Oscillatory variations of cutaneous blood flow were studied using laser Doppler flowmetry in 20 newborns. Simultaneous monitoring of cardiorespiratory state was also performed. The frequency and amplitude of oscillatory curve varied, even on identical skin regions in each infant. When their respiration and heart rate were irregular, the frequencies of oscillatory curves were significantly higher and with a larger amplitude than when cardiorespiratory function was regular. The frequencies of oscillatory curves at two symmetrical points of an individual were not different, but a significant difference in the oscillatory cycle was recognized at two asymmetrical points. Distributions of peak-to-peak time periods of oscillatory curves were studied in nine healthy and four sick newborns. Seven of nine healthy newborns had more than two peaks in their distributions, while only one peak with a narrowly-spread distribution was observed in the four sick newborns with almost exclusively periodic breathing throughout monitoring. In conclusion, we speculate that cardiorespiratory state and some neurogenic control affects the variations observed. In addition, the narrowly-spread distribution of each time period appeared to be an important indicator of morbidity. PMID- 1414333 TI - Balloon valvuloplasty for congenital aortic valve stenosis in an infant and children. AB - Percutaneous balloon aortic valvuloplasty (BAV) was performed in 14 patients, including one critically ill infant with congenital valvular aortic stenosis (AS). BAV was effective in 13 patients (except the infant). The peak systolic pressure gradient between the left ventricle (LV) and the ascending aorta decreased from 76.6 +/- 21.6 to 29.5 +/- 15.3 mmHg (P less than 0.001). Follow-up cardiac catheterization was performed for eight patients between 1 and 3 years (1.6 +/- 1.1 years) after BAV. Restenosis was found in only one patient, and the efficacy of BAV continued significantly. Aortic regurgitation developed or increased in severity in 5 of 13 children immediately after BAV. Any other severe complication was not observed. Dilatation by BAV was not sufficient for the infant with critical AS, and acute myocardial infarction (AMI) in the lateral wall of the LV occurred during the BAV procedure. The infant died 3 days after the procedure due to AMI. It was concluded that the retrograde double balloon technique was superior to the retrograde single balloon technique. In two cases, the single balloon technique was ineffective because it was impossible to fix the balloon at the aortic annulus. However, the double balloon technique was effective in every patient. BAV is effective for AS in children, and an optional repeat trial may enable BAV to be the first choice for AS. Although BAV may be effective for neonates and infants with critical AS as an emergency treatment, much attention must be paid during the procedure. PMID- 1414334 TI - Methacholine inhalation challenge in children with idiopathic chest pain. AB - Bronchial reactivity to inhaled methacholine (MCH) was evaluated in 32 patients with 'idiopathic' chest pain. Each pain was recurrent in nature. The incidence of cases with a provocative concentration causing a 20% fall in the forced expiratory volume in 1 sec (PC20) of 10 mg/ml or less was 62.5% (20 cases), while it was only 11.1% (three cases) in 27 healthy controls. Seventeen patients had no personal history of allergic diseases, elevated serum IgE level or positive house dust mite-specific IgE antibody. Among these 17, eight (47.1%) had a PC20 of 10 mg/ml or less, the incidence of which was also higher than that of the healthy controls. During the challenge, eight patients complained of chest pain similar to that experienced before. The present results indicate that bronchial hyper reactivity is an important cause of 'idiopathic' chest pain. Patients with unexplained chest pain should be considered for inhalation challenge. PMID- 1414335 TI - The measles outbreak in Chikuhou District, Fukuoka, Japan, 1990: correlation between herd immunity level and outbreak size. AB - A measles outbreak occurred in the Chikuhou district of Fukuoka, Japan from May to October 1990, during which 71 patients were cared for at the Itoda Public Hospital. Hospital records revealed a large outbreak in the adjacent town of Kanada. In order to characterize the outbreak, questionnaires were sent to all preschool-age children in Itoda (73% effective response) and in Kanada (76% effective response) requesting information about their vaccination and/or history of measles. The number of patients was 22 (4%) in Itoda and 63 (14%) in Kanada, most of these being preschoolers, while the vaccination rate was 61% and 44%, respectively. The herd immunity levels in age-specific groups were compared between the two towns. Before the epidemic, the immunity level of 1 year old children in Kanada, who showed the higher attack rate, was lower (18%) than that in Itoda (39%), while after the epidemic it rose above 60% in both towns. When we studied the correlation between the attack rate and the vaccination rate, or the number of children susceptible to measles (susceptibility rate) in each preschool, the attack rate correlated negatively with the vaccination rate (correlation coefficient [CC] = -0.818; P less than 0.01), and positively with the susceptibility rate (CC 0.860; P less than 0.01). The regressed equation on the correlation indicated that the immunity level should be more than 70% to keep the attack rate under 5% in preschools. After the epidemic, the immunity levels of all preschoolers reached above 70%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414336 TI - Prenatal diagnosis in high risk pregnancies for Zellweger syndrome. AB - Zellweger syndrome is a lethal disorder. At present, no effective therapies are known for the patients of Zellweger syndrome. Recently a typical case of Zellweger syndrome in Japan was observed. In spite of intensive care, the patient died at the age of 3 months. Following this, the parents requested prenatal diagnosis for their following two pregnancies. We investigated levels of very long chain fatty acids (VLCFA), levels of bile acids in amniotic fluid and immunoblotting of peroxisomal beta-oxidation enzymes in cultured amniocytes. We report that immunoblotting using cultured amniocytes is an effective method for prenatal diagnosis of Zellweger syndrome. Furthermore, if we use immunoblotting for prenatal diagnosis, we can discriminate pseudoZellweger syndrome from pseudoneonatal adrenoleucodystrophy. Following prenatal diagnosis, two healthy babies were delivered. After birth, no abnormal levels of VLCFA in either serum or red blood cell membranes were confirmed. In this paper, we report that we can diagnose a healthy fetus in a high risk pregnancy for Zellweger syndrome. PMID- 1414337 TI - Cardiac beriberi (shoshin beriberi) caused by excessive intake of isotonic drink. AB - A 21 month old female had voluntarily ingested 0.5-1.51 of isotonic sports drink daily from 10 months of age. She developed hyponatremia and beriberi heart disease, which resulted in metabolic acidosis and cardiogenic shock (shoshin beriberi). Mechanical ventilation was applied for pulmonary edema. Right heart failure was improved after administering vitamin B1. However, 5 days after the shock, hypoxemia and diffuse radiographic infiltrates progressed, and a diagnosis of adult respiratory distress syndrome (ARDS) was made. After the occurrence of an air leak, the patient died of respiratory failure. The cardiogenic shock and pulmonary edema due to cardiac beriberi may have triggered the ARDS. PMID- 1414338 TI - Disseminated intravascular coagulation syndrome in anorexia nervosa. AB - A 15 year old boy with anorexia nervosa developed disseminated intravascular coagulation syndrome (DIC). Because of severe cachexia he had been admitted to the Shimane Prefectural Central Hospital. During his hospitalization he developed generalized massive ecchymosis. Laboratory data revealed not only DIC but also multiple organ complications. The patient was treated intravenously with FOY (gabexate mesilate, a protease inhibitor), heparin, a transfusion of fresh frozen plasma, antithrombin III concentrates and platelets. Intravenous hyperalimentation was also administered. The laboratory data, the general condition and the emotional state of the patient improved remarkably. We emphasize the importance of keeping in mind coagulopathy as a complication in anorexia nervosa. PMID- 1414339 TI - Long duration of erythrocyte hypoplasia after bone marrow transplantation. AB - Bone marrow transplantation was performed on a 15 year old girl with chronic myelogenous leukemia. The bone marrow was obtained from her younger sister, who was human leukocyte antigen haplo-identical but major ABO incompatible. As a result, the condition of pure red cell aplasia (PRCA) persisted over a long period of time. In order to overcome major ABO incompatibility, erythrocytes were eliminated from the bone marrow graft before transplantation, and methotrexate and cyclosporine (CsA) were used to prevent graft-versus-host disease (GVHD). Administration of erythropoietin proved ineffective. B19 parvovirus infection could not be detected during that time. Agglutinin titers decreased to less than fourfold in parallel with the recovery of erythrocytes. Reports on similar PRCA have been limited to cases of transplantation with ABO incompatibility and cases where CsA was administered to prevent GVHD. This suggests that ABO incompatibility and CsA might be related to the development of PRCA. PMID- 1414340 TI - A case of ulcerative colitis induced by oral ferrous sulfate. AB - We report a case of ulcerative colitis (UC) in a 15 year old female undergoing treatment for anemia with oral ferrous sulfate. We suggest that the oral ferrous sulfate initiated the typical symptoms of UC in this case. This case is the first clinical report to our knowledge supporting the 'iron-catalysed oxidant-mediated ischemic injury theory' of UC. PMID- 1414341 TI - Gallbladder changes in neonatal hepatitis: markedly thickened wall and lack of contractility. AB - The gallbladder wall changes were observed on ultrasonography during the course of a patient with neonatal hepatitis. The gallbladder was not detected at 53 days of age, but on the next day its wall was observed to be markedly thickened and without contraction following the administration of cerulein. It had a thinner wall at 57 days of age and reacted to cerulein. The wall thickness and contractility went together with the improvement of jaundice and liver function tests. Histological diagnosis was compatible with neonatal hepatitis. Ultrasonographic detection of the gallbladder has been helpful to differentiate neonatal hepatitis from biliary atresia. It is reported to be compatible with neonatal hepatitis to detect a normal-sized gallbladder or its contraction following cerulein administration or feeding. Since this case did not meet these criteria initially, thickened wall of the gallbladder may be an additional finding indicating neonatal hepatitis. The importance of repeated ultrasonography and clinical correlation was stressed. PMID- 1414342 TI - Immature gastric teratoma in an infant. AB - A 45 day old boy presented with progressive abdominal distension, tarry stools and anemia. A plain roentgenogram of the abdomen showed irregular, coarse calcifications in the left upper quadrant. The ultrasonography and computerized tomography of the abdomen revealed a large heterogeneous tumor with calcified parts in the left hemiabdomen. At operation, a 12 cm x 11 cm x 10 cm, multilobular, exogastric and endogastric tumor, including a portion of the anterior wall of the stomach, was extirpated. The pathological examination revealed a gastric teratoma with immature neural elements. Eight years after the total excision of the tumor there has not been any recurrence. This study includes a review of 88 cases (including the present case) of gastric teratoma reported in the English and Japanese literature. PMID- 1414343 TI - Repressive adaptation and family environment. AB - The hypothesized connection between adaptive style, specifically repressive adaptation, and the family environments of adolescent clinical samples was investigated. Adolescent patients (n = 221) were studied, who were then divided into four groups matched for sex, age, and socioeconomic status (mean age = 15.7 years, SD 2; sex = 14% boys, 86% girls; SES = 2.4). Grouping was based on the Marlowe Crowne Social Desirability Scale and Spielberger's Trait Anxiety Inventory Scores [repressors (n = 43), impression managers (n = 54), high anxious (n = 55) and low anxious (n = 69)]. Results by MANOVA, Scheffe and discriminate function analysis confirmed our hypothesis. Repressors had distinct family environments as measured by the Family Environment Scale (p = 0.0001). Families were characterized by high levels of cohesion, expressiveness, independence, and organization, displaying correspondingly low levels of achievement orientation, conflict, control and incongruence. Repression may be an effort to adapt to an idealized family environment. PMID- 1414345 TI - General event representations of young children in a child psychiatric clinic. AB - Thirty-nine Children (5-8 years old) in a child psychiatric clinic and 50 5-year old and 50 7-year-old schoolchildren were interviewed about two events: "getting dressed" and "a day in school". Both the children in the clinical and in the normal group formed general representations of these events. Children in the clinical group mentioned fewer acts, props and locations. Nearly all the children in both groups described how one gets dressed in the correct temporal order, but fewer children in the clinical than in the normal group described a day in school in the correct temporal order. Fewer children in the clinical than in the normal group gave causal explanations. Within the clinical group children with cognitive/attentional deficits tended to have less complete and less organized representations than children whose primary problems are relational. PMID- 1414344 TI - An evaluation of the effectiveness of psychiatric treatment on adolescent in patients and out-patients. AB - The psychopathology of 33 adolescents (11 inpatients and 22 out-patients) was measured by a variety of standardized and non-standardized instruments, immediately prior to treatment (baseline), and 10 weeks later (outcome). Their parent were assessed on measures of current mood and personality traits, over the same time interval, also on quality of life, marital satisfaction, and amount of contact with family, friends and relatives, at baseline only. Together with extensive measures of family life and demography, a psychosocial profile of subjects and their families was obtained. The demographic homogeneity of the sub groups was demonstrated, the only significant differences being that in-patients were older, and out-patients' households larger. Significant clinical differences at baseline were also few; all in-patients were clinically disordered, as were 19 out-patients. There was an even spread of disorders (conduct, emotional, and mixed) between sub-groups. Parents of in-patients rated their children as more disordered than out-patient's parents rated their children. Outcome measures, including the repeated measure of child psychopathology, indicated more significant and substantial trends for improvement over baseline conditions for in-patients than for out-patients, although both sub-groups were less disordered, overall. Both sub-groups of mothers were depressed at baseline, and out-patients' mothers remained so, at outcome. Anxiety in mothers of in-patients was significantly less at outcome. Personality traits among both sub-groups of parents were similar, showing slight introversion and neuroticism, and these traits remained stable over time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414346 TI - The outcome of childhood suicidal behaviour. AB - A group of children under 16 years of age who were admitted to hospital after episodes of deliberate self-poisoning, were followed up after one year. Ninety of the original sample of 100 were traced, and interviewed. Almost half of the subjects were improved after one year but the remaining children continued disturbed. Improvement was most marked in relation to "school problems" and "running away from home". There was significant improvement for some children in their family relationships. Ten per cent of children had been involved in further self-poisoning during the follow-up period. Extended follow-up some seven years later traced 41 of the original subjects. The repetition rate for self-poisoning was 20% although the majority of these episode occurred within a year of the original self-poisoning. Overall, the situation of subjects was judged as improved by them and their families although significant psycho-social difficulties remained for some. PMID- 1414347 TI - The hyperkinetic child. A historical review. AB - A historical review of the concepts and classification of the hyperkinetic child is presented, ranging from the supposed biological origins in the late nineteenth century to the hyperkinetic impulse disorder, and then to the concept of minimal brain dysfunction. The differences in European and North American approaches are described. PMID- 1414348 TI - Savant capabilities of autistic persons. AB - Various savant abilities, mostly those in intellectual fields, found in autistic people, namely in music, memory, mathematics, specific knowledge and drawing, are presented. Their social importance is discussed. As an interpretation three hypotheses are offered. In autistic people perception and storing of perceived impulses function differently from in normal people (comparable to those of eidetics). The memory process and the storing function abnormally. Outstanding abilities are reinforced unilaterally by the environment and are produced as a kind of avoidance material, because many usual abilities cannot be performed. PMID- 1414349 TI - Music therapy in the treatment of autistic children. Medico-sociological data from the Federal Republic of Germany. AB - Related to the theoretical research on the use of music therapy in the treatment of autistic children there was made a postal survey about the attitude towards and the application of music therapy. The data of established paediatricians and paediatric institutions in FRG show that music therapy is already accepted in the treatment of autistic children. The implications of these medico-sociological data are discussed. PMID- 1414350 TI - Treatment of incarcerated offenders. Possibilities and problems. AB - The author discusses in detail the operations of a prison treatment program for youthful offenders. Although a model program and an exception to the typical prison, the treatment program had problems. One is the inherent difficulty of working with anti-social people. The other, analyzed in detail, is the unpleasant nature of many of the prison staff, several of whom were unqualified to work in a treatment setting. Suggestions are made for humanizing the staff. PMID- 1414351 TI - Self-organisation of cognitive processes and psychosis. Development and test of a theoretical model. AB - The development of a theory of self-control of brain processes leads to a model of disturbance of integration of brain processes in psychotic persons. The theory is that the "novelty-familiarity relation" of the current state of the processed information normally dominates the current mode of information processing. In the second part of the study adults with schizophrenia in remission and children with infantile autism were tested as to the manner in which they used newly introduced elements. The psychotic persons took the different character of the new elements less into consideration. The difference from the normal control persons is significant. PMID- 1414352 TI - Naltrexone open trial with a 5-year-old-boy. A social rebound reaction. AB - The neurobiological rationale for an opiate antagonist pharmacotherapy of autism is presented. Naltrexone efficacy in decreasing autistic behaviour and in increasing social-affiliative behaviour was explored in a 5-year-old autistic boy. Naltrexone (0.5 mg/kg 3 times peer week) was effective in immediately decreasing gross motor activity and stereotyped behaviour and caused a delayed increase of crying, smiling and rough-and-tumble play. This single case presents preliminary evidence that a therapeutically valuable rebound reaction is possible and that the human opioid system modulates social-affective processes. The possibility of psychological factors being instrumental in achieving this effect is discussed as being suitable for future clinical trials. PMID- 1414353 TI - Early intervention for children in trouble. Educational and health system in Iceland. PMID- 1414354 TI - The Benton test in school counselling diagnostics. An exploratory study. AB - The Visual Test is subject to a critical appraisal, according to the standards of psychological tests. Investigating the test results of clients from a school counselling service it is shown that this test does not comply with the requirements of item analysis and reliability; referring to validity this test might be useful to estimate the general intelligence of pupils. PMID- 1414355 TI - Defense style and adaptation in adolescents with depressions and eating disorders. AB - Maturity of defense style has been associated with the level of adaptive functioning, but few studies have assessed defense style using self-report questionnaires which can provide ratings with great reliability and objectivity. We compared self-perception of defense style (using Bond's Defense Style Questionnaire) with ratings of adaptation assessed retrospectively by two independent raters (using the DSM III-R Global Assessment of Functioning scale) in a population of 100 adolescent girls diagnosed as having either an eating disorder or depression. There was significant correlation between maturity of defense style and level of adaptation, with greater maturity of defense style being associated with higher levels of adaptive functioning. This effect was independent of diagnosis within this population. PMID- 1414356 TI - Effects of nicotinamide and its isomers on iron-induced renal damage. AB - The effects of three isomers of pyridinecarboxamide (picolinamide (2 pyridinecarboxamide), nicotinamide (3-pyridinecarboxamide) and isonicotinamide (4 pyridinecarboxamide)) on iron-induced renal damage were studied. Pyridinecarboxamide (250 mg/kg body weight, ip) was administered 10 min before injection of ferric nitrilotriacetate (Fe(III)-NTA) (7.5 mgFe/kg body weight, ip). In picolinamide-treated rats, the renal tubular necrosis induced by Fe(III) NTA was attenuated and serum creatinine did not increase. Picolinamide most efficiently suppressed renal lipid peroxidation in vivo-induced by Fe(III)-NTA. Non-heme iron levels in the kidneys after Fe(III)-NTA injection did not differ in groups to which pyridinecarboxamides were administered. To elucidate the protective effects of picolinamide, we studied the action of pyridinecarboxamides on lipid peroxidation and DNA damage in vitro. These isomers inhibited iron induced lipid peroxidation of linolenic acid. Picolinamide had no effect on DNA damage, but nicotinamide and isonicotinamide promoted DNA damage by iron, especially when ascorbate was used as a reductant. None of these pyridinecarboxamide isomers changed the chlelate structure of Fe(III)-NTA as shown by electronic absorption spectra. Among the three isomers, picolinamide most effectively protected the kidneys against iron-induced renal damage, since it not only inhibited iron-induced lipid peroxidation, but also had little enhancing action on DNA damage by iron. PMID- 1414357 TI - Characterization of transmural and subendocardial infarction by typing and grading of ischemic lesions in autopsied human hearts. AB - Two types of myocardial infarction, transmural and subendocardial, were macroscopically examined, and the gross and microscopic findings were correlated. The transmural type usually consisted of yellowish-brown coagulation necrosis in the center of an infarcted focus and coagulative myocytolysis at the marginal zone. The subendocardial type was characterized by coagulative myocytolysis throughout the entire focus. Wavy fiber and colliquative myocytolysis of non specific ischemic lesions were seen only microscopically in both peripheral and subendocardial areas of infarcted foci. Coagulation necrosis was associated with obstructive thrombus formation in 79% of cases as a result of absolute ischemia in the transmural type. Coagulative myocytolysis was associated with obstruction by plaque hemorrhage in 27% of cases, and multivessel disease was frequently encountered in the subendocardial type due to insufficient blood supply. Based on histochemical and immunohistochemical examinations, the ischemic lesions were graded in descending order of coagulation necrosis, coagulative myocytolysis, wavy fiber, and colliquative myocytolysis. The close relation between coagulation necrosis and the transmural type as well as that of coagulative myocytolysis with the subendocardial type suggests two different pathogenetic mechanisms of transmural and subendocardial infarction. PMID- 1414358 TI - Primitive neuroectodermal tumors of bone and soft tissue. With reference to histologic differentiation in primary or metastatic foci. AB - Primitive neuroectodermal tumors (PNET) of the bone and soft tissue were reviewed by immunohistochemistry and partly by morphometry, focusing particularly on histologic changes in recurrent or metastatic foci, in order to elucidate their probable histogenetic relationship with Ewing's sarcoma (ES) and its extraskeletal counterpart (EES). Eleven cases of bone tumor (average patient age; 15.1 yr) and 12 cases of soft tissue tumor (average patient age; 22.1 yr) which disclosed unequivocal Homer-Wright rosettes and/or at least foci of ganglion cell differentiation either in a given primary tumor or metastatic (or recurrent) foci were selected from small round cell tumors primarily categorized as ES or EES. Most of the cases for which follow-up biopsy samples were available disclosed prominent Homer-Wright rosettes in the metastases, whereas the primary tumors showed features of ES and lacked rosettes. In only one case, Homer-Wright rosettes were absent in the metastatic tumor. Most cases had been treated by combined intensive chemotherapy and radiotherapy, which might have influenced cell differentiation. Neural markers (neuron-specific enolase, neurofilament protein and others) were positive in most cases. Three cases with otherwise typical histologic features of ES or EES showed minute foci of ganglion cell differentiation, as confirmed by morphometry and neural markers. These results suggest that ES (or EES) and PNET are histogenetically related, but represent different stages of cell differentiation. PMID- 1414359 TI - Light chain nephropathy in a 19-month-old boy with AIDS. AB - A 19-month-old boy with AIDS developed clinically unexplainable proteinuria. Biopsied renal tissue was examined by light microscopy, transmission electron microscopy, and immunofluorescence. Findings included an increase of mesangial matrix with occasional nodular sclerosis, mesangial hypercellularity, and glomerular deposits of kappa and lambda light chains. There were deposits of kappa, but not lambda, light chains in the arteriolar walls, and around the tubular and interstitial capillary basement membranes. Quantitative urinary immunoelectrophoresis revealed an extremely high urinary concentration of kappa light chain. These changes are diagnostic of light chain nephropathy. The rarity of light chain nephropathy in childhood and its occurrence in a patient with AIDS make this case unusual. PMID- 1414360 TI - Cardiac rupture complicating hemorrhagic infarction after intracoronary thrombolysis. AB - An 80-year-old woman with acute myocardial infarct received intracoronary thrombolysis by a large dose of urokinase four hours after the onset of chest pain. Despite the patient having no chest pain after intracoronary thrombolysis and her general condition being stable, she died suddenly on the 4th hospital day. Autopsy revealed hemopericardium due to cardiac rupture, which occurred at the center of the transmural hemorrhagic infarction of the anteroseptal wall. The massive hemorrhagic infarction was promoted by reperfusion from thrombolytic therapy. She had also classic risk factors for cardiac rupture, such as hypertension, senility, female gender, and first acute myocardial infarct. Therefore, the present case demonstrated that hemorrhagic infarction increased the incidence of cardiac rupture. PMID- 1414361 TI - Unusual huge intramuscular granuloma with calcium phosphate crystal deposition in the buttock. AB - An unusual case of a huge granuloma featuring marked calcium phosphate crystal deposition in muscle is presented. A 58-year-old male demonstrated a well circumscribed, large, elastic firm mass which had slowly grown over 8 years in the left buttock. Clinical examinations including X-ray, ultrasonography and computed tomography all suggested a neoplastic growth. Surgical excision revealed three inter-connected irregular-shaped masses, measuring up to 11 x 10 x 6 cm in size. The histological appearance was of granulomas composed of numerous small crystals surrounded by reactive mononuclear cells embedded in fibrous tissue containing many foreign body type giant cells. Chemical analysis demonstrated the crystals to be made up of calcium phosphate. PMID- 1414362 TI - [Synthesis of 2 beta-(4'-methyl-1'-piperazino)-3 alpha-hydroxyl-16,17- substituted-5 alpha-androstanes]. AB - According to some studies, the vicinal amino-alcohol compounds of 5 alpha androstane possess to a certain extent biological activities in cardiovascular system. In order to find new antiarrhythmic agents, seven new 2 beta-(4'-methyl 1'-piperazino)-3 alpha-hydroxyl-16, 17-substituted-5 alpha-androstanes were synthesized through 2 alpha,3 alpha-epoxyl-5 alpha-adrostan-17-one from epiandrosterone. Preliminary results of biological experiment showed that they possess to a different extent antiarrhythmic activities among which compounds VI, XI and XIV showed higher activities than others. PMID- 1414363 TI - [Selective long-range DEPT NMR technique and its application to structural study of glycoside]. AB - This paper reports a new NMR technique: selective long-range DEPT. The result obtained showed that the technique can be used to assign NMR signal of 13C, 15N and 31P nuclei, and connect the spin systems separated by quaternary carbon or heteroatom. This paper deals mainly with applying the technique for determining the glycosidation position in aglycone moiety and sequence of sugar moiety in a natural glycoside. PMID- 1414364 TI - [The structure identification of pyridinemono terpene isocantleyine]. AB - Siphonostegia chinensis Benth. as a traditional Chinese medicine "liujinu" has been used for centuries in China, but up to date little has been reported about its chemistry. Now, four compounds have been isolated from the aerial parts of this genus. On the basis of spectroscopic analysis (UV, IR, MS, 1HNMR, 13CNMR and 2D-NMR) and chemical evidences, compound I was shown to be a new pyridinemonoterpene alkaloid which is a stereoisomer of the known compound cantleyine, and named isocantleyine. Its structure was determined as 5H-2 pyridine-4-carboxylic acid, 6,7-dihydro-6-hydroxy-7-methyl-methyl ester. Compound III was identified as the known compound loliolide. The other two (II and IV) are still under investigation. This paper deals mainly with the structure identification of compound I. PMID- 1414365 TI - [Studies on the chemical components of Rhodiola crenulata]. AB - Six chemical components I-IV were isolated from the roots of Rhodiola crenulata (Crassulaceae). Five (I-V) of them were identified as known salidroside (I), p tyrosol(II), pyrogallol, gallic acid, and beta-sitosterol, based on comparison of its Rf(TLC), mmp and spectral data with those of authentic samples. The sixth component was found to be a new delta 1-isopentenyl-3-O-beta-D-glucopyranoside and named crenulatin(VI). Its structure was confirmed on the basis of its spectral data (IR, MS, 1H- and 13C-NMR). PMID- 1414366 TI - [Isolation and identification of yibeissine]. AB - A new steroidal alkaloid, yibeissine (II), with a know alkaloid (I) was isolated from the bulb of Fritillaria pallioiflora Schrenk by column chromatographic techniques. Their structures have been determined based on spectral and chemical data. PMID- 1414367 TI - [Studies on iridoid glycosides from Swertia angustifolia]. AB - Five secoiridoid glycosides were isolated from Swertia angustifolia Buch. -Ham. ex D. Don. The structures of two new compounds, angustiamarin (I) and angustioside (II) with three known compounds sweroside (III), swertiamarin (IV) and epi-eustomoside (V) were elucidated by means of spectroscopic and chemical methods. PMID- 1414368 TI - [Quantitative analysis of compound injection of aminopyrine by dual-wavelength linear regression spectrophotometry]. AB - A dual-wavelength linear regression spectrophotometry has been introduced and evaluated. Depending on a group of standard mixture solutions the optimal wavelengths and calibration curve can be determined simultaneously by linear regression method. The deviation of absorption resulting from molecular interaction can be calibrated by this method and the results are more accurate. The validity of this method has been confirmed through its use in the analysis of compound injection of antipyrine with satisfactory recoveries. Results obtained by Kalman filtering (KF), partial least squares (PLS) and target factor analysis (TFA) are also given. PMID- 1414369 TI - [Studies on first derivative differential pulse polarography and its applications]. AB - First derivative differential pulse polarography was developed and used for the quantitative analysis of chlorphenamine maleate, haloperidol, pyridoxine and their preparations. The method is simple, swift, sensitive and accurate. PMID- 1414370 TI - [The kinetics of ascorbic acid oxidation catalyzed by Cu(II)/H2DCA in the presence of DNA]. AB - In phosphate buffer (pH 7.40), at 20.00 +/- 0.05 degrees C, the visible spectra of Cu(II) and Cu(II) complexes and the kinetics of ascorbic acid oxidation catalyzed by Cu(II)/H2DCA in the presence of DNA were studied. Measurements were reported on rate of .OH formation by the oxidation of ascorbic acid in the presence of Cu(II)/H2DCA. It showed that ternary complex Cu(II)/H2DCA/DNA may exist in the system in which DNA strand was broken by ascorbic acid in the presence of Cu(II)/H2DCA, and it was assumed that the DNA-breaking action of ascorbic acid in the presence of Cu(II)/H2DCA conformed to site-specific Fenton reaction mechanism. All the result of DNA-breaking action can be explained in terms of this site-specific Fenton reaction mechanism. PMID- 1414371 TI - [X-ray diffraction studies on tolbutamide solid dispersion]. AB - D860 (tolbutamide) solid dispersions prepared with urea, polyvinyl pyrrolidone (PVP), and polyethylene glycal (PEG) 6000 as carriers were studied by X-ray diffraction, relating to their dissolution rates. D860 in D860-PVP dispersion was shown to be in an amorphous state and to have greater dissolution rate. D860-urea and D860-PEG melts were found to be partly in miscible solid solution state and partly in microcrystal state and possess higher activity and greater dissolution rate. D860-PEG coprecipitate was a physical mixture and its dissolution rate is slower than its melt. No variation in the crystal structure of the D860 dispersions was observed during the ageing test. PMID- 1414372 TI - [Synthesis and antitumor activity of beta-germanyl-alpha-amino acid derivatives]. AB - Some beta-germanyl-alpha-amino acid derivatives were prepared from the reaction of HGeCl3 with substituted oxazolines. The compositions of the above compounds were studied using IR, element analysis and so on. Experimental results were as follows: for 1-substituted-2-amino-2-carboxyethylgermanium susquioxide (such as IIIb), the po LD50 for mice was found to be above 10 g/kg. When given ip, a maximum inhibition of 50% of the growth of S180 was obtained for IIIb, whereas an inhibition of 42% was achieved for 5-Fu under the same experimental condition. PMID- 1414373 TI - [Determination of active constituents in shi-wei (Folium Pyrrosiae) by high performance liquid chromatography]. AB - A new analytical method for the simultaneous determination of three constituents, viz, mangiferin, isomangiferin and chlorogenic acid in Folium Pyrrosiae using high performance liquid chromatography was developed. A Zorbax-CN column (4.6 mm x 25 cm) was used; methanol--water--phosphoric acid (pH 2.5) (20:80:0.1) was used as the mobile phase. The method was rapid, sensitive, precise and showed good reproducibility. The three constituents in crude drugs were completely separated within 15 min. Recoveries of three constituents were 96.78-101.3%, with coefficients of variation 1.8-4.7%. Mangiferin and isomangiferin were separated for the first time. Pyrrosia plant materials were analyzed as follows: The powdered sample was refluxed with methanol for 4 hours, the extract was transferred into a 25 ml volumetric flask and diluted to 25 ml with methanol. A definite amount of this sample solution was injected for HPLC. The content of constituents in Folium pyrrosiae was calculated from the relevant peak height or peak area. The content of these three constituents in 7 species of Chinese Pyrrosia collected in 17 districts were determined. The results showed that these constituents varied greatly with the plant species and varied with the districts for the same species also, and should be evaluated accordingly. PMID- 1414374 TI - [Studies on secondary derivative differential pulse polarography and its applications]. AB - Secondary derivative differential pulse polarography was developed and used for the quantitative analysis of ribostamycin sulfate, kanamycin and their preparations. By using sodium hydroxide-potassium dihydrogen phosphate solution as the base solution, ribostamycin sulfate and kanamycin showed good peaks at 0.105 V and -0.37 V (vs Ag/AgCl) respectively. The linear relationship of ribostamycin sulfate and kanamycin between concentration and peak height was obtained in the concentration range of 1.8-10.8 x 10(-4) mol/L and 3.1-18.6 x 10( 4) mol/L and the determination limit was 7.2 x 10(-9) mol/L and 4.6 x 10(-8) mol/L respectively. This method is simple, rapid and sensitive. The result is accurate. PMID- 1414375 TI - [Measurement of dopamine in rat striatum in vivo with a biomicroelectrode made from mixed plant tissue-carbon paste]. AB - The mixed plant tissue-carbon paste electrode was prepared and their electrochemical characteristics were investigated. The sensitivity and selectivity of this bioelectrode were found to be good because of the utility in biocatalysis. It may work continuously with high stability for 10 h in vivo. The principal advantages of the new bioelectrodes are shorter in response time and longer in stability. These advantages meet the requirements of in vivo determination. Using these electrodes, the dopamine contents in rat striatum were measured by anodic stripping voltammetry. The drug-induced changes in dopamine levels were monitored. From the results, we can conclude that the biomicroelectrode is a very economic biosensor for its low cost and easiness to prepare and is a valuable tool for studying dopamine function. It will provide a good method for the evaluation of drug actions on dopamine neurones. PMID- 1414376 TI - [The lead generation of protein tyrosine kinase inhibitors by quantitative structure-activity relationship analysis]. AB - Analysis of the quantitative relationship between a series of substituted benzylidenemalononitriles and the inhibitory action on protein tyrosine kinases were carried out using the Hansch-Fujita method. The results indicate that the presence of two or three hydroxy groups attached to a phenyl ring, which connects an extended (trans form) conjugated chain, is essential to the inhibition. Compared with the structure of other kinds of inhibitors, a presumable basic structure for inhibiting the enzyme was generated. PMID- 1414377 TI - [Antioxidative effect of three water-soluble components isolated from Salvia miltiorrhiza in vitro]. AB - The antioxidative effect of three water-soluble components isolated from Salvia miltiorrhiza has been investigated. All the three components were found to inhibit both NADPH-vit C and Fe(2+)-cysteine induced lipid peroxidation (malondialdehyde formation) in rat brain, liver and kidney microsomes in vitro. The order of their inhibitory effect is as follows: salvianolic acid A, salvianolic acid B and rosmarinic acid. The inhibitory effect on lipid peroxidation induced by NADPH-Vit C was more than that induced by Fe(2+) cysteine. In addition, the three compounds lowered the production of superoxide anion radical (O2-) in xanthine-xanthine oxidase system. The order of their potency was similar to that in antilipoperoxidation. The above results suggest that the three components have strong antilipoperoxidant activity in vitro, which may be partly through scavenging O2-.. PMID- 1414378 TI - [Effect of arteether on Schistosoma japonicum]. AB - NIH mice infected with Schistosoma japonicum cercariae for 3, 7, 14, 21 or 35 d were treated ig either with arteether or artemether at the daily dose of 100-200 mg.kg-1 for 2 d, the efficacy produced by both drugs was similar. The d 7 schistosomules and d 35 adult worms were more susceptible to arteether or artemether with respective worm reduction rates of 77.5%-87.2% and 51.7%-61.3%. Histological and histochemical studies showed that d 7 and d 35 schistosomes, harbored in mice treated with arteether 300 mg.kg-1.d-1 for 2 d appeared in cloudy swelling and vesiculation in the tegument, distension of intestine, apparent decrease or even disappearance of glycogen and inhibition of alkaline phosphatase activity in the tegument and parenchymal tissues, as well as formation of dead worm granuloma. PMID- 1414379 TI - [Studies on biotransformation of etheofazine in isolated perfused rat liver]. AB - The biotransformation of etheofazine (EDMTP), a new anticancer drug, was studied by using isolated perfused rat liver. Two main metabolites were separated from the perfusate by HPLC and TLC and their chemical structures were determined by MS, 1H-NMR and IR. EDMTP-I is the parent compound. EDMTP-II is 7-ethyl-8 aminotheophylline. EDMTP-II was also separated and identified from the blood of mice after iv of 10 mg/kg. Species difference of biotransformation of EDMTP between rat and mouse seems to be not significant in this study. PMID- 1414380 TI - [Acute and chronic hypotensive effect of m-nifedipine]. AB - Three groups of adult stroke--prone spontaneously hypertensive rats (SHRsp) were treated with m-nifedipine (m-Nif) 2.5, 5 and 10 mg.kg-1 by intraperitoneal injection. The systolic blood pressure (SBp) decreased significantly. The hypotensive effect persisted for 2-4, 6-8, and 12 h respectively and the peak effect appeared in 1 h. The range of hypotension was markedly greater than that of nifedipine (Nif). In SHPsp, treatment with m-Nif 10 or 30 mg.kg-1.d-1 for 4 weeks reduced significantly the SBp, but the hypotensive action is about the same as Nif. PMID- 1414381 TI - [Studies on the alkaloids of Cephalotaxus. VII. Structures and semi-synthesis of two anticancer cephalotaxine esters]. AB - Two new alkaloids, namely neoharringtonine (1) and anhydroharringtonine (2) with significant antileukemic activity were isolated from Cephalotaxus fortunei Hook f.. Their structures have been established by spectral analyses and semi synthesis. Seven known alkaloids, deoxyharringtonine (3), isoharringtonine (4), isocephalotaxinone (5), acetylcephalotaxine (6), cephalotaxine (7), harringtonine (8) and homoharringtonine (9), were also isolated and identified. PMID- 1414382 TI - [Studies on the alkaloids of Cephalotaxus. IX. Semi-synthesis of cephalotaxine esters and their anti-leukemic activity]. AB - Harringtonine, homoharringtonine, deoxyharringtonine and isoharringtonine isolated from Cephalotaxus plant are the esters of cephalotaxine with significant inhibitory activity against P-388 leukemia. In this investigation seventeen new esters of cephalotaxine type alkaloids have been synthesized. Preliminary pharmacological examination showed that compounds 1, 2, 2 + 3, 6 and 8 showed similar antileukemic activity as homoharringtonine. Compounds 4, 5, 15 and 16 showed moderate inhibitory activity. Some structure activity correlations of these esters were discussed. PMID- 1414383 TI - [Studies on the chemical constituents of Annona squamosa]. AB - Twelve compounds were isolated from Annona squamosa. Their structures were identified as liriodenine (AS-1), moupinamide (AS-2), -(-)-kauran-16 alpha-ol-19 oic acid (AS-3), 16 beta, 17-dihydroxy-(-)-kauran-19-oic acid (AS-4), anonaine (AS-5), 16 alpha, 17-dihydroxy-(-)-kauran-19-oic acid (AS-6), (-)-isokaur-15(16) en-17,19-dioic acid (AS-7), squamosamide (AS-8), 16 alpha-methoxy-(-)-kauran-19 oic acid (AS-9), sachanoic acid (AS-10), (-)-kauran-19-al-17-oic acid (AS-11), daucosterol (AS-12). Among them, AS-8 is a new amide, AS-9 is a new natural product. PMID- 1414384 TI - [Application of 2D NMR techniques in the structure determination of chrysanthetriol]. AB - Chrysanthemum indicum L. is a Chinese traditional drug used for antifebrile, detoxication and hypotensive purposes. In continuation of our efforts to search for the active principles of this species, a new sesquiterpene compound, named chrysanthetriol was isolated from the more polar fraction of the title plant. Chrysanthetriol is a colorless oil, [alpha]D20-31.8 degrees (c 0.3, MeOH). HRMS showed the molecular formula to be C15H26O3. The structure and stereochemistry of chrysanthtriol was elucidated as I by the use of 1H-1H COSY, 1H-13C COSY, 1H-13C COLOC 2D NMR spectroscopy. PMID- 1414385 TI - [The application of circular dichroism on the structure analysis of natural products--diterpenoid dilactones and tylophorines]. AB - In this paper, circular dichroism (CD), sector projection and reverse octant rule projection of four diterpenoid dilactones and five tylophorines (two of them, 6, 8, are new compounds) are reported in which reverse octant rule projection is the first application to the configuration determination of diterpenoid dilactone. By using these rules, the predicted Cotton effects of these compounds coincided with the result of previous determinations, so, their absolute configurations are assigned. PMID- 1414386 TI - [Structure of lamiophlomiol C]. AB - A new highly oxygenated iridoid, lamiophlomiol C isolated from the alcohol soluble fraction of the roots of Lamiophlomis rotata (Labiatae), was shown to have the molecular formula C11H14O7. On the basis of UV, IR, MS and NMR spectroscopic data, particularly X-ray crystallographlic analysis, structure I has been assigned to this iridoid. PMID- 1414387 TI - [Studies on the triterpenoid saponin of Cinopodium chinense (Benth) O. Kuntze]. AB - A new triterpenoid saponin named clinopodiside was isolated from Clinopodum Chinense (Benth) O. Kuntze. The structure of clinopodiside A was elucidated by spectroscopic and X-ray diffraction analysis as 3-O-beta-D-glucopyranosyl (1--- 6)-[beta-D-glucopyranosyl (1----4)]-beta-D-glucopyranosyl-olean-11, 13 (18)-diene 3 beta, 16 beta, 23, 28-tetrol. PMID- 1414388 TI - [Computer-aided prediction of optimal composition of multicomponent mobile phase in high performance liquid chromatography]. AB - This paper proposed a systematic optimizing method for the composition of multicomponent mobile phase in high performance liquid chromatography. A new chromatographic response function (CRF) has been constructed according to the fundamental retention equation and rule of peak width at half-height, and the optimal composition of multicomponent mobile phase can be automatically predicted by a computer with CRF. This paper improved the known complex method, therefore, the optimal mobile phase composition in the global area may be found by means of this modified complex method. The optimal separation conditions of four vitamins and three nitrophenols were determined by use of the optimizing method reported in this paper. The results predicted by the computer were verified by the experimental data obtained in HPLC using ternary mobile phase. PMID- 1414389 TI - [Studies on analysis of Belladonna alkaloids by capillary GC and GC-MSD]. AB - A method for analyzing belladonna alkaloids--hyoscyamine, scopolamine, anisodamine and anisodine, by means of capillary GC and GC-MSD was described. The retention data and characteristic ions of the parent and TMS derivatives of these alkaloids are given and will be very useful for identification of unknown alkaloids. The derivatization of different silylation reagents was compared, and the derivatization with MSTFA was found to be better than with BSA and BSTFA. The method has been used for studying biotransformation of these alkaloids in biosynthesis. Analysis of anisodamine and anisodine by CGC and GC-MS has not been found in the literature. In addition, the advantages of TMS derivatization are also discussed. PMID- 1414390 TI - [Study on pilules of indomethacin--PEG 6000]. AB - Indomethacin (IDM)-PEG 6000 pilules were prepared using PEG 6000 as the carrier. The solubility of IDM in IDM-PEG 6000 pilules was about twice as much as pure IDM. When the effective dose of IDM-PEG 6000 was only half that of IDM tablet, the irritation of IDM-PEG 6000 pilule on rat stomach was reduced significantly but it still manifested the action of inhibiting the secretion of basal gastric acid. PMID- 1414391 TI - [Development of rapid-dissolution armillarisin-A tablet and study on its choleretic action in rats]. AB - For increasing the choleretic action of armillarision-A, a new formulation of rapid-dissolution tablet (A) was developed. The effect of A, a marketed amillarisin-A tablet (B) and a armillarisin-A Na sterile power (C) on rats biliation in vivo were investigated. The dissolution rates of A and B were also determined. The results demonstrate that the choleretic action of A is equal to C but superior to B, and the dissolution rate of A is higher than B. Moreover, the armillarisin-A dissolved percentage of A in vitro at time t was well correlated with the biliation net accumulative amount in vivo at time 3t. PMID- 1414392 TI - [Synthesis and properties of 3,17-disubstituted estrogenic steroids]. AB - In order to develop new radio protectors of low estrogenic activity and high potency and to study the structure-activity relationships, 10 estrogenic steroids were synthesized from the view point of drug latentiation, and by substitution with active groups in different positions of the steroidal skeleton. The compounds were tested in mice for estrogenic activity and radioprotective effect. The results showed that the introduction of hydroxyalkylimido or hydroxy group into 17-position resulted in reduction of estrogenic activity. Hydroxyalkylimides (2d, e) showed better protective effect in 750 rad of 60CO gamma-irradiation in mice by the reduction of radiation dose of 144-156 rads than estradiol (reduction of 62.2 rad). Whereas 2a-c and 4a, b showed weak or no protective effect. Compounds 1, 3, and 5a, b increased the 30-day survival rates by 35-80% in mice exposed to 900 rad of irradiation, when administered ip 0.1 mg per mouse 24 h before irradiation. PMID- 1414393 TI - Should be biologic marker be sensitive and specific? AB - Potential biologic markers in psychiatry are often subjected to tests of sensitivity and specificity. However, in many instances, clinically diagnosed diseases may not be truly singular in their pathophysiology, and these tests may be inappropriate. One may distinguish between diagnostic markers useful in clinical pathology, linkage markers specifying genetic location and pathophysiologic markers that are primarily valuable as research tools. The latter are probably most useful in present-day psychiatry but they may not be sensitive or specific in their correspondence to clinical diagnosis. PMID- 1414394 TI - Exploration and support in psychotherapeutic environments for psychotic patients. AB - Clinical experience and previous investigations suggest that insight-oriented milieu therapy with psychotic patients presupposes a specific balance of explorative and supportive factors in the milieu. Explorative and supportive factors were translated here to two optimal ward atmosphere profiles using the subscales in the Community-oriented Programs Environment Scale (COPES) as profile variables. Three Swedish therapeutic communities for psychotic patients were then studied by means of COPES. The study showed distinct patterns in these units regarding deviations from the optimal profiles, differences in the balance between the explorative and supportive factors, divergences between explicit treatment philosophy and the perceived ward atmosphere, and differences between patient and staff perceptions of the ward atmosphere. These patterns followed a continuum from a self-governing, nonhierarchical and nonmedical organization to a hierarchical unit that is an integral part of the medical care organization. The conclusion was that a beneficial psychotherapeutic environment requires consistency in the applied treatment model, including an organization and setting that corresponds to the explicit treatment philosophy, well mirrored in the patients' perceptions. PMID- 1414395 TI - Discriminant validity of a reduced set of Mini-Mental State Examination items for dementia and Alzheimer's disease. AB - Linear discriminant analysis was used to construct a series of discriminant functions including subsets of demographic variables and Mini-Mental State Examination item responses for a case series and a population sample. A 9-item discriminant function including the variables for time orientation, recall, calculation, copying a figure, age, writing, 3-step command, naming, and race distinguished demented subjects from community controls with 91% sensitivity and 88% specificity. The same discriminant function classified Alzheimer's disease patients and controls with 96% sensitivity and 98% specificity. This discriminant function has been cross-validated as a potential screening instrument for Alzheimer's disease in a community-based sample. PMID- 1414396 TI - Detecting psychopathology in young adults: the Young Adult Self Report, the General Health Questionnaire and the Symptom Checklist as screening instruments. AB - This study compares the screening capacity of an age-adjusted child-oriented questionnaire, the Young Adult Self Report (YASR) with two adult-oriented questionnaires, the General Health Questionnaire-28 (GHQ-28) and Symptom Checklist-90 (SCL-90) in a sample of young adults (18-25 years). The YASR performed just as well as the SCL-90 and both performed better than the GHQ-28. The relatively poor performance of the GHQ-28 compared with the YASR and SCL-90 could not be attributed to instrument characteristics or to the use of referral status as indicator of psychopathology. In assessing psychopathology in young adults an age-adjusted child-oriented instrument might be a good alternative to the existing adult-oriented instruments, especially when one takes into account the problem of data comparability over time in longitudinal studies in which children are followed into adulthood. PMID- 1414397 TI - The course of thyroid abnormalities during lithium treatment: a two-year follow up study. AB - A total of 116 patients on lithium treatment were followed up for 2 years to determine the course and the clinical relevance of thyroid abnormalities. Elevated thyroid-stimulating hormone (TSH) concentrations were transitory in most patients, except those with serum antithyroid antibodies. The patients who initially had microsomal antibodies remained positive, with an increase in titre in two-thirds of cases. Three young patients of both sexes developed thyroid autoimmunity early in the treatment. The risk of developing hypothyroidism was higher in women, especially in the presence of antibodies. TSH concentrations were significantly lower when carbamazepine was combined with lithium. PMID- 1414398 TI - The thyrotropin response to thyrotropin-releasing hormone as a predictor of response to treatment in depressed outpatients. AB - We evaluated the predictive value of the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in 32 depressed outpatients completing a double-blind placebo-controlled trial of s-adenosyl-l-methionine (SAMe), which failed to show any significant difference between SAMe and placebo. Treatment response was defined as the change in Hamilton Rating Scale for Depression (HRSD 24) score between baseline and the end of the six-week trial. Subjects with TSH response outside the normal range (7-25 uU/ml) had a significantly greater response than patients with a normal response. There was also a significant correlation between absolute deviations from the mean TSH response (16 uU/ml) and changes in HRSD-24 scores. PMID- 1414399 TI - Cases of buprenorphine abuse in India. AB - Buprenorphine was introduced as a potent analgesic with low abuse potential. Reports of buprenorphine abuse by opiate abusers have accumulated over the years, highlighting its use as a cheap alternative to heroin. The lower potency compared with heroin is being compensated by using a cocktail of buprenorphine with benzodiazepines or cyclizine. This study of 18 cases seen over 3 years broadly confirms these findings. Four cases reported haematemesis during acute withdrawal, a symptom not reported in earlier studies. PMID- 1414400 TI - Clinical staging of dementia in a population survey: comparison of DSM-III-R and the Washington University Clinical Dementia Rating Scale. AB - In a population survey in Stockholm, 224 dementia cases were staged using two scales: the Washington University Clinical Dementia Rating Scale and DSM III-R. Both scales had to be modified by adding additional specifications and, in the case of DSM III-R, a new category of questionable dementia. After modification, the comparison of the two scales showed good agreement when all stages were analyzed (kappa = 0.60), but moderate agreement on the questionable and mild stages (kappa = 0.47). These results confirm the staging of mild dementia as the most problematic issue. Finally, the scales both showed moderate agreement with the categorized Mini-Mental State Examination (MMSE) (0-17 for severe and moderate forms; 18-23 for mild cases). Our data suggest new cut-off points for the MMSE when used as a staging scale. PMID- 1414401 TI - Antidepressants may not assist recovery in practice: a naturalistic prospective survey. AB - A total of 130 people attending psychiatric hospitals within 6 months of onset or relapse of an episode of depressive disorder were interviewed about their symptoms and treatment at the time of their initial contact. After a mean 4-month interval, 119 were reassessed to test the hypothesis that patients treated with antidepressants would be significantly more likely to be clinically improved compared with those untreated. Severity and duration of the episode emerged as the only significant clinical predictors of clinical improvement. Patients on treatment with antidepressants at the start of the study showed a nonsignificant trend for a lesser degree of clinical improvement, even when clinical severity and compliance were taken into account. Those who were not commenced on treatment until later in the study also fared no better than those who were never prescribed antidepressants. The effect of low doses of antidepressants (almost always a tricyclic) appeared to be less beneficial than either higher doses or clinical management without antidepressant drugs. The need for further experimental and naturalistic studies conducted over various periods of time and the implications for clinical practice, medical audit and the appropriate use of health outcome indicators are discussed. PMID- 1414402 TI - The Nordic concept of reactive psychosis--a multicenter reliability study. AB - Reactive psychosis is a common diagnosis in the Nordic countries (Norway, Sweden, Denmark, Finland and Iceland) and in several other parts of the world. In ICD-9 and DSM-III-R, the concept is defined more narrowly than in the Nordic tradition. In this study we examined the interrater reliability of the Nordic concept by the case-summary method between clinicians from 9 university departments in the Nordic countries. The results show that Nordic psychiatrists have a reasonably reliable concept of reactive psychosis, and that this psychosis can be diagnosed as reliably as schizophrenia and affective psychosis. PMID- 1414403 TI - Suicidal acts on metro systems: an international perspective. AB - Suicide is a problem experienced by railway networks worldwide. The epidemiology of this method of suicide has not been described in any detail. To investigate the characteristic features of railway suicide, data were gathered from 23 metro systems around the world. The similarities in the nature of this problem across systems were striking. Universally the victims were young (aged less than 40 years); most incidents involved men; case fatality was generally less than 60%; there was no consistent seasonal variation in incidence; the peak time of day for incidents was 1000-1200; proximity to psychiatric institutions was possibly a risk factor. This method of suicide may be prevented by environmental modification of the railway system. Strategies for reducing the opportunities for suicide on railways are discussed. PMID- 1414404 TI - The Bible suicides. AB - Death by suicide is described in the Holy Bible. The number of characters affected ranges from 3 to 11, depending on the inclusion of the Apocrypha, the definition of suicide adopted and the version of the death accepted when there is more than one account. The Bible treats suicide in a factual way and not as wrong or shameful. PMID- 1414405 TI - Risk of deliberate self-harm and factors associated with suicidal behaviour among asymptomatic individuals with human immunodeficiency virus infection. AB - The study was aimed at evaluating the risk of deliberate self-harm (DSH) and factors associated with suicidal behaviour in 213 asymptomatic individuals with human immunodeficiency virus (HIV) infection in 3 transmission categories (68 gay men, 123 intravenous drug users and 22 heterosexuals). The results showed that 12 HIV-seropositive (HIV+) subjects were involved in DSH after the notification of a positive HIV test result, of which 8 occurred within 6 months and 4 between 6 months and 3 years. HIV+ subjects with a past psychiatric history showed a 7.7 fold increase in the relative risk of DSH, and HIV+ subjects with a history of DSH showed a 5-fold increase in the relative risk of DSH compared with HIV+ individuals without a past psychiatric history and a history of DSH. Professionals involved in the care of HIV+ individuals need to be aware of this risk, especially in the first few months after notification of HIV status and also at later stages of acquired immunodeficiency syndrome. PMID- 1414406 TI - Suicides in the former Soviet republics. AB - The suicide rate in the former Soviet Union rose from 17.1 per 100,000 inhabitants in 1965 to 29.6 in 1984. In regions of long-standing traditional lifestyles, strong religious faith and multi-generation families (the Caucasus and central Asia), the suicide rate was low, whereas in regions with sociopolitical antagonisms (Baltic States) and forced social changes (Russia), it was high. A significant decline in the suicide rate (34.5%), from 29.6 to 19.4 per 100,000 inhabitants, occurred in 1984-1988 throughout the Soviet Union, in the hopeful period of social democratization and stiff restrictions on the sale of alcohol. Rates varied widely between different republics - from 1.8 in Armenia to 26.3 in Lithuania and 24.3 in the Russian Soviet Federated Socialist Republic (RSFSR) in 1988. In contrast to the pattern in several countries in western Europe, the suicide rates in the Russian SFSR were much higher in the rural regions than in the urban ones. PMID- 1414407 TI - Trends in psychiatric hospitalization in Denmark: a 10-year register-based investigation. AB - Information about all admissions to psychiatric hospitals and departments in Denmark in 1977, 1982 and 1987 and about all resident patients on census days in the same years were extracted from the central psychiatric register. The number of available beds decreased by 43% from 1977 to 1987. The admission rates decreased for all diagnostic groups but schizophrenia, which increased. The group of younger schizophrenic men declined in size, which is alarming if mentally ill homeless people are considered. The census study shows a decrease in all diagnostic groups, most pronounced in the elderly age groups. Patients with neuroses disappear from the available beds in the mental hospitals and departments. The changes in the psychiatric service system from mostly hospitalization to outpatient treatment and community psychiatric treatment require a comprehensive personal registration of treatment regardless of the administrative affiliations of these services. PMID- 1414408 TI - Therapeutic sleep deprivation in a depressed patient: prolongation of response with concurrent thyroxine. AB - A 53-year-old woman with major depression was studied throughout 7 trials of therapeutic sleep deprivation (SD). Under conditions where the patients was either medication-free or receiving antidepressant therapy, improvement with SD was followed by full relapse on returning to sleep. Four SD sessions conducted while the patient was receiving thyroxine each resulted in remission, sustained for several days. These results suggest that the beneficial effects of SD may be mediated by thyroid hormones, or associated activity in the hypothalamic pituitary-adrenal axis. PMID- 1414409 TI - Miscounting suicides. PMID- 1414410 TI - Distressing behaviour of schizophrenics at home. AB - The care of mentally ill people at home is being encouraged nowadays. As a result, the family members feel an increased burden of care and find it difficult to cope with the care of a schizophrenic patient at home. We interviewed the relatives of 62 schizophrenics systematically regarding the behaviour of the patients that was perceived to be distressful. This was done using the Scale for Assessment of Family Distress. It was noted that behaviours related to activity and self-care were perceived to be most distressful, and not aggressive or psychotic behaviour. Distress was more often reported by younger relatives and those with more education. The findings have implications in planning appropriate family intervention methods. PMID- 1414411 TI - A population-based survey of the characteristics of high school students with and without a history of suicidal behavior. AB - In a sample of 570 15- and 16-year-old normal high school students, the characteristics of those with and without a history of suicidal behavior were compared. In a written inquiry, information was obtained on family background, emotional and behavioral problems, sexual and physical abuse and suicidal thoughts and behavior. Differences between the students with and without a history of suicidal behavior were statistically analyzed for boys and girls separately by a matched control design. The results for both boys and girls indicated that the experience of sexual abuse, feelings of loneliness, depressed mood, low self-esteem and the use of drugs were particularly strongly related to suicidal thoughts and behavior; for girls, physical abuse and for boys, low self reported academic achievement appeared to be clearly related aspects. Furthermore, the strong interrelations between all of these variables is underlined, suggesting a multi-problem background of youngsters with a history of suicidal behavior. PMID- 1414412 TI - Incidence of anorexia nervosa in Denmark. AB - From 1970 to 1989, 915 people were admitted for the first time to psychiatric institutions in Denmark and had as their main diagnosis an eating disorder, ICD-8 306.50-59. The incidence of these admissions increased from 0.42/100,000 population in 1970 to a maximum of 1.36/100,000 in 1988. During the time of our investigation, the number of discharges of patients with an eating disorder as the main diagnosis was constant from somatic hospitals, whereas discharges from psychiatric institutions increased. PMID- 1414413 TI - Reciprocated self-disqualification among parents of schizophrenics. AB - Is deviant parental communication an interactional phenomenon? If it is, is this interaction stronger or weaker among parents of schizophrenics (S) than among parents of non-schizophrenic psychiatric controls (NS) and normals (N)? These two questions were investigated by using sequential analysis of parental interaction during Spouse Rorschach. Parents' deviant communication was measured by the self disqualification (SD) category in the Relationship Control Coding System. Results showed that self-disqualification clearly depended on the quality of the previous parental communication: an SD utterance greatly increased the probability of an SD response from the spouse among S (n = 17), NS (n = 15) and N (n = 14). However, this increased probability was significantly higher among S parents. Furthermore, S parents' communication was significantly less dependent on their own previous communication than NS and N parents' communication was. However, the sheer magnitude of parental SD communication was a significant predictor of offspring diagnosis even when the interaction between the spouses was controlled for. Thus, the results indicate that the high rate of deviant communication among S parents is partly due to individual characteristics of the parents and partly due to reciprocation of the other spouse's deviant communication. The results are discussed with reference to possible gene-environment interaction in both schizophrenia and deviant communication. PMID- 1414414 TI - Vigilance deficits in schizophrenics and affectively disturbed patients. AB - Vigilance is a concept associated with the early levels of information processing. Vigilance deficits have repeatedly been found in schizophrenic patients. It has not been clear, however, whether such cognitive dysfunctions are specific to schizophrenics or not. In this study, 28 schizophrenics were compared with 19 affectively disturbed patients and 17 normals on a vigilance test that is a hybridization of a Continuous Performance Test (CPT) and a Span of Apprehension Test (SAT). The results showed that schizophrenics performed significantly below the normals only on target hits on the CPT. There were no differences between the two patient groups, either on number of correct hits or on commission errors. On the SAT measures, normals performed better than the two psychiatric groups on all measures. Schizophrenics had more commission errors than the affectives, but there were no differences between the two groups with respect to target hits. Neither CPT nor SAT deficit, thus, seem to be specific schizophrenic characteristics. PMID- 1414415 TI - Risk factors for depression in elderly people: a prospective study. AB - In 1982-1983 a random sample of 1486 people aged 65 years and above was generated from general practitioner lists; 1070 were interviewed in the community using the Geriatric Mental State and a Social History questionnaire. The cohort was followed up by interview 3 years later. At year 3 the diagnostic computer program AGECAT diagnosed 44 incident cases of depression. Information from the depressed group's initial and further interviews was compared with a control group (which excluded cases of affective or organic mental illness). Univariate analysis yielded three factors that were significantly associated with the development of depression 3 years later: a lack of satisfaction with life; feelings of loneliness; and smoking. Multivariate analysis confirmed their independent effects and revealed 2 further factors attaining significance: female gender and a trigger factor, bereavement of a close figure within 6 months of the third-year diagnosis. Some other factors traditionally associated with depression, such as poor housing, marital status and living alone, failed to attain significance as risk factors. PMID- 1414416 TI - The effect of long-term lithium treatment on the mortality of patients with manic depressive and schizoaffective illness. AB - Clinical research centers in Aarhus, Berlin, Hamilton and Vienna collected mortality data for 827 manic-depressive and schizoaffective patients given lithium treatment for more than 6 months. The average duration of the treatment was 81 months and the total time on lithium 5600 patient-years. For each patient, the mortality risk was calculated by entering the appropriate national life tables for the general population. The number of observed deaths was 44; the number of expected deaths was 49.7. The standardized mortality ratio, 0.89, did not differ significantly from 1.0. The mortality of manic-depressive patients is 2-3 times that of the general population. Our data show that the mortality of manic-depressive and schizoaffective patients given long-term lithium treatment does not differ significantly from that of the general population. PMID- 1414417 TI - Somatization in primary care: pattern and correlates in a clinic in Nigeria. AB - During a study of mental disorder in a primary care clinic in Nigeria, 214 patients, selected on the basis of their scores on the General Health Questionnaire, were interviewed with the Composite International Diagnostic Interview, a structured clinical interview that allows for a systematic assessment of somatization symptoms. Only 1.1% of this clinical sample fulfilled the DSM-III-R criteria for somatization disorder, but 4.7% and 10.8% met the criteria for somatoform pain disorder and undifferentiated somatoform disorder, respectively. Age, gender and the presence of a DSM-III-R diagnosis of depression or dysthymia accounted for significant variability in the number of reported somatization symptoms. On factor analysis, a factor with close similarity to DSM III-R somatization disorder was obtained. This factor is associated with the demographic features commonly found among patients with DSM-III-R somatization disorder. PMID- 1414418 TI - Does an attempted suicide actually have a cathartic effect? AB - It has been suggested in empirical studies that an attempted suicide has a cathartic effect. However, only one study used a control group of depressives who had not attempted suicide. A replication of these results using more strictly defined patient groups and a more comprehensive assessment of the psychopathology during index treatment was not possible. Major depressives with and without suicide attempts before index admission displayed similar courses of their depressive symptoms and somatic complaints during index treatment. The cathartic effect of a suicide attempt may be restricted to a severe major depression or to a violent suicide attempt. PMID- 1414419 TI - Trends in suicide rates among military conscripts. AB - The purpose of this study was to analyse the trends in suicide rates among conscripts in Finland and to compare them with suicide rates in men of the same age in the general population. The suicide rates among conscripts slightly increased from the mid-1960s until the mid-1970s, but this rise was less marked than among young men in the population as a whole. In the 1970s and 1980s, the suicide mortality among conscripts was half of that among civilian men of the same age in the population. The implications for suicide prevention are discussed. PMID- 1414420 TI - The Parental Bonding Instrument in adolescent patients with anorexia nervosa. AB - The Parental Bonding Instrument (PBI) was administered to 54 adolescent patients with anorexia nervosa. Scores were compared with those of matched groups of normal and of nonanorectic adolescents referred for assessment to an adolescent psychiatric unit. Significant differences between the 3 groups were demonstrated with respect to care and protection dimensions. Overall scores of subjects in the anorectic group resembled those of normals rather than those of referred patients. Anorexia nervosa patients described their fathers and mothers as being more caring and their mothers as being less overprotective than did psychiatrically referred peers. The study raised questions concerning the use of the PBI in adolescents, in particular those with anorexia nervosa, and the role of the family in the aetiogenesis of this condition. PMID- 1414421 TI - The course of alcohol amnestic disorder: a three-year follow-up study of clinical signs and social disabilities. AB - Forty-four patients with alcohol amnestic disorder were prospectively studied from 1987 to 1990. The cognitive impairment, social disability and mental symptoms of patients under different conditions were compared. Thirty-three patients (75%) had no symptoms of Wernicke's disease nor a medical history to suggest its existence. The course of mean cognitive impairment of patients in different settings was stable. Change in intelligence quotient correlated with alcohol consumption during the study. The development of social disability differed remarkably in different settings. Patients in a large nursing home deteriorated and patients in small-scale sheltered accommodation improved. PMID- 1414422 TI - Extent and determinants of burden among families of patients with affective disorders. AB - The burden of care experienced by family members of 90 patients with major affective disorder was evaluated. The extent of burden in these families was considerable. The burden was significantly more among families of bipolar patients than those of major depression. Prolonged illness and high levels of dysfunction among patients correlated consistently with severity of burden. Severity of illness, higher age of the patient and number of episodes of the illness also influenced the extent of burden. Variables such as gender of the patient, religion, education, occupation, family type and size and the locus of control of both patients and relatives did not influence the extent of burden significantly. These results have substantial implications for the planning of intervention strategies. PMID- 1414423 TI - Parasuicide during Ramadan in Jordan. AB - To investigate the impact of national and religious events on the rate of parasuicide, a comparison was made between the number of reported parasuicides during the month of Ramadan and the month before and after Ramadan in Jordan, for the years from 1986 to 1991. Significantly fewer parasuicides were reported during Ramadan than the month preceding it and the month that follows Ramadan. The findings confirm previous observations that national events reduce the rate of parasuicide, but the protective effect does not persist into the month that follows Ramadan. PMID- 1414424 TI - Angiographic methods for the study of fluid mechanical factors in atherogenesis. AB - The purpose of this thesis is to investigate the feasibility of using angiographic methods to study, in vivo, fluid mechanical phenomena believed to influence the development and localization of atherosclerotic lesions, in particular, separated flow. This involved developing a method to recognize separated flow by digital analysis of cineangiography films, testing this method both with model measurements and in a clinical material, and a detailed analysis of certain methodological problems. In addition, methods have been developed to measure the tortuosity of arteries, a phenomenon which may, according to fluid mechanical theory, promote the occurrence of separated flow. In a glass model of an arterial bifurcation, a pump generated a pulsatile flow resembling that in large arteries. Using LDV (laser Doppler velocimetry) as a reference method, three velocity profiles in the symmetry plane of the model were recorded. During diastole, extensive separated flow was demonstrated in the larger branch of the bifurcation. The flow was then cineradiographed during injection of contrast medium, and the image sequence was transferred to an image analysis workstation. Treating the image sequence as a set of time-intensity curves, time parameters representing the arrival time of the contrast agent were computed. In the resulting parametric images, zones of delayed filling were identified and found to correspond to the separated flow. Viscosity was measured for seven radiographic contrast media and, as expected, the highest values were found for the largest molecules. For iohexol and ioxaglate, which were studied in detail, a linear relation to temperature and a quadratic relation to concentration were found. Whole-blood viscosity was measured for 5 healthy volunteers at high and low shear rates, before and after mixing with contrast agents in varying proportions. At low shear, viscosity decreased, while at high shear, it increased with increasing contrast concentration. The conclusion was that modern contrast media, despite their higher viscosity, seem to affect blood rheology less than older agents. In a study of the imaging characteristics of the digitization equipment for cinefilms, the resolution proved comparable to that of an entirely digital system, while the noise level was higher. Algorithms for the correction of variations in exposure and geometric distortion are also presented. The method for analysis of cinefilms, tried in the model study, was applied, with slight modifications, to a material of 26 patients with hyperlipidemia and slight or moderate atherosclerosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1414426 TI - Do physicians need assistance to help smokers quit? PMID- 1414425 TI - Do women under the care of family physicians have fewer cesarean sections? PMID- 1414427 TI - The usefulness of matched pair randomization for medical practice-based research. AB - To be feasible, study designs for most intervention research in primary care settings must limit the number of participating physicians, without sacrificing the statistical power required to test the research hypotheses. A model was developed to examine sample size and statistical power requirements when using the physicians' practice as the unit of analysis. Randomized designs using either matched or unmatched samples of practices were compared under varying conditions. When baseline variability is small or the number of practice pairs is large, matching at best marginally increases power. However, in the typical case when baseline variability is large or the number of practice pairs is small, matching substantially increases the power to find intervention effects with a smaller sample. Thus, matching prior to randomization could improve the design of many intervention studies in primary care settings. PMID- 1414428 TI - Specialty differences in primary cesarean section rates in a rural hospital. AB - To evaluate if physician specialty is a factor in determining whether cesarean sections are performed, a retrospective review of all obstetrical records was performed at a rural hospital in northeastern Kentucky. Review of 1522 patients who delivered between January 1, 1987, and June 30, 1989, showed that staff obstetricians had a 10.8% cesarean rate compared with 8.9% for family physicians. Analysis of the diagnoses that led to cesarean delivery showed no difference between the specialties for cesarean sections performed for fetal distress, preeclampsia, or other high-risk problems, but obstetricians had an increased cesarean section rate for cephalopelvic disproportion (10.7% of all deliveries vs 6.3% for family physicians, P less than 0.001). These results suggest that physician specialty may influence cesarean section rates, although other factors could also contribute to these results. PMID- 1414429 TI - Cesarean section rate: a comparison between family physicians and obstetricians. AB - This retrospective study compared the cesarean section rates of family physicians and obstetricians for low-risk pregnancies. The study populations (n = 492) were demographically similar. The overall cesarean section rate for the study was 7.5%. Chi-square analysis revealed a statistically significant higher rate of cesarean section for obstetricians compared to family physicians. Obstetricians were overall three times more likely to deliver by cesarean section than were family physicians (11.3% compared to 3.8%). This pattern persisted for normal length Stage I and Stage II labors. Equal cesarean section rates were noted in prolonged labor patterns. The rate of fetal distress, meconium, or other complications was equal between family physicians and obstetricians; equivalent fetal outcomes and Apgar scores were noted. None of the studied patient factors explained the difference in cesarean section rates between family physicians and obstetricians. PMID- 1414430 TI - Does nurse counseling or offer of nicotine gum improve the effectiveness of physician smoking-cessation advice? AB - Medical advice and use of nicotine gum have recently received increased attention as effective tools to encourage smokers to quit, yet the relative value of nurse vs physician counseling has not been explored in depth. In this study, 425 smokers attending three urban primary care centers in Barcelona were systematically allocated to one of three groups: group A patients received a brief counseling session to quit from their family physician; group B patients were given the same brief counseling along with a free supply of nicotine gum; group C received a brief health-education session from the primary care nurse. Three hundred forty-nine patients (82%) could be reached by telephone at the two month follow up. By that time, after correcting for the estimated validity of the phone report of smoking status, the proportion declaring themselves to be nonsmokers was 10.9%, 11.1%, and 10.8%, respectively, without significant differences between them. At one-year follow up the proportions were 4.4%, 5.3%, and 6.0%. In the logistic regression analysis, only the expected difficulty of quitting was predictive of one-year abstention, OR = 3.1 (95% CI: 1.3-7.3). The present study shows no difference between physician versus nurse counseling and no improvement in the proportion of quitters with the addition of nicotine gum in the physician-counseled group. PMID- 1414431 TI - An analysis of 2846 industrial illnesses and injuries seen in a family practice. AB - We analyzed 2846 industrial illnesses and injuries in 2430 patients seen in a family practice with a large occupational medicine component over a three-and-a half-year period. Of the 268 medical diagnoses made, back injuries and cumulative trauma disorders to the upper extremities comprised the majority. A large number of pesticide and chemical exposures were also seen. Consultations were obtained in 16.7% of the cases and 61.7% of the cases were closed as resolved. There were 17 patients hospitalized and no deaths. We recommend that family practice residents be trained in the procedures and laws of the workers' compensation system as well as in treating specific occupational health problems. PMID- 1414432 TI - Recurrent bacterial vaginosis: association with vaginal sponge use. AB - A hypothesis-generation study was conducted to examine risk factors for bacterial vaginosis recurrences among women participating in a randomized controlled trial of male sexual partner treatment. Of the 140 women enrolled in the trial, 72 had a normal vaginal gram-stained slide at the first follow-up visit and were included in this analysis. Nineteen of the 72 (26.2%) women developed a bacterial vaginosis recurrence documented by a vaginal gram-stained slide during the 6-week follow-up period. Of the 19 women, 4 of 6 sponge users (66%) developed a bacterial vaginosis recurrence (RR 2.93, 95% CI: 1.43-6.02). Logistic regression analysis supported the association between sponge use and bacterial vaginosis recurrences (adjusted RR 2.71, 95% CI: 1.06-6.99) but revealed that an apparent protective effect of diaphragm use was due to the confounding effect of sexual partner treatment. Our hypothesis is that bacterial vaginosis recurrences may be due to factors other than sexual transmission, such as sponge use. Further studies are needed to examine risk factors for bacterial vaginosis recurrences. In the interim, physicians might suggest another form of contraception to their sponge-using patient with frequent bacterial vaginosis infections. PMID- 1414433 TI - Tangible assistance: a simple measure of social support predicts pregnancy outcome. AB - The association between tangible assistance, a single-item measure of social support, and serious perinatal complications was prospectively measured in 548 rural pregnant women. Those 38 women who reported no or one reliable helper in the third trimester (low tangible assistance) had a higher rate of poor outcomes (at least one of the following: neonatal death, transfer to neonatal intensive care unit, birthweight less than 2500 g or 5-min Apgar score less than 7) than those with 2 or more helpers (13.2% vs. 5.7%, p = 0.08). All of the increase in poor outcomes occurred in women with high sociodemographic risk (at least one of the following: age less than 18, no male partner, or less than high school education). In this subgroup of 121 women, the difference in poor perinatal outcomes was striking (28.6% vs. 7.6%, p = 0.03). The association between tangible assistance and poor outcome remained after controlling for biomedical risk. A simple question about the availability of supportive companions may be clinically useful. PMID- 1414434 TI - Perceived core procedural skills for Nebraska family physicians. AB - We conducted a mail survey of 287 practicing family physicians, 22 family practice faculty, and 60 family practice residents in both rural and urban Nebraska concerning their perceptions of "core" procedures in family medicine and their perceived competency in performing them. Final response rate was 45%. There was general agreement concerning what constituted the core procedures in family medicine, although several newer procedures, such as flexible sigmoidoscopy, provoked more controversy. Rural physicians were more likely to classify intrauterine device insertion, endometrial biopsy, and cervical biopsy as core procedures than their urban counterparts. As expected, whether a physician performed a procedure related directly to his reported competence in performing it. However, there were discrepancies between perceived training during residency and current practice for control of nasal hemorrhage, aspiration of breast mass, flexible sigmoidoscopy, endometrial biopsy, and joint aspiration. Faculty programs for teaching procedural skills, standards for documenting competence, and systems for ongoing quality assurance should be further developed. PMID- 1414435 TI - Cefoxitin-induced antibiotic resistance in Enterobacter species in the community hospital. AB - The aim of this study was to determine whether beta-lactamases could be induced by cefoxitin in the community hospital, since this problem of antibiotic resistance has been shown to exist at the tertiary care level. One hundred sixty six Enterobacter species isolated from patients in two community hospitals in Dayton, Ohio, were tested for cefoxitin induction of beta-lactamase production by a disk-approximation method. Piperacillin and cefoxitin disks were placed in approximation to each other on Mueller-Hinton plates inoculated with Enterobacter species with appropriate controls. Three Enterobacter strains (1.8%) showed truncation of the zone of inhibition (indicating beta-lactamase induction) with sensitivity to both cefoxitin and piperacillin. However, 84 strains (50.6%) showed truncation around the piperacillin disk with resistance to cefoxitin. One hundred fifty (90.0%) strains showed resistance to cefoxitin. These data indicate that cefoxitin induction of beta-lactamases in Enterobacter species is indeed a potential problem in incurring antibiotic resistance in the community hospital. PMID- 1414436 TI - Office-based colonoscopy in a family practice. AB - A total of 112 patients, 64 women and 48 men, underwent 157 in-office colonoscopies with intravenous sedation. A total of 113 polyps were found. Thirty polyps were of the diminutive (less than 0.6 cm) hyperplastic (metaplastic) or nonneoplastic type. Forty-three were of the diminutive adenomatous, or villous, neoplastic type, and 40 were neoplastic but larger than 0.6 cm. Biopsies and polypectomies were done. There were no instances of perforation, hemorrhage, or other major complications. A spectrum of other colorectal pathology was found, the majority of which was treated in the office. Patients were risk stratified for surveillance according to polyp histopathology, with nonneoplastic polyps assigned no risk, and neoplastic polyps assigned high risk status. This study demonstrates that for the most reliable prognostication and risk stratification, all polyps should be removed for histopathological assessment. PMID- 1414437 TI - Influences on specialty choice of family physician graduates of a tertiary care medical school. AB - A survey of 392 University of Michigan Medical School family physician alumni who graduated from medical school between 1950 and 1984 explored factors influencing respondent specialty choice and satisfaction with specialty choice. The strongest influences on specialty choice were the opportunity to treat a variety of illnesses, know patients personally, and work with people as opposed to things. The traditional medical school setting offered an environment of high-quality education, opportunities to see a variety of illnesses, and a model of tertiary, uncoordinated, discontinuous care that the respondents were determined not to replicate in their own medical careers. Fifty-nine percent of the respondents had no reservations about their decision to become family physicians, 74% said they would return to the University of Michigan if they were to enter medical school again, and 91% were greatly or moderately satisfied with their choice, indicating their satisfaction with their career choice and medical school. PMID- 1414438 TI - Effects of serotonin on intracellular calcium in embryonic and adult Helisoma neurons. AB - The neurotransmitter serotonin has been shown to regulate neurite outgrowth in many embryonic and adult Helisoma neurons. To determine whether intracellular calcium concentration is also regulated by serotonin in large numbers of neurons, the calcium indicator Fura 2 was used to measure intracellular calcium in mass dissociated cultures of embryonic and adult neurons. Comparisons between embryonic and adult neurons revealed that embryonic neurons have a narrow population distribution of rest intracellular calcium levels around relatively low values. In contrast, the population distribution for adult neurons covered a much wider range of rest calcium concentrations. In both embryonic and adult cultures, serotonin induced a shift in the population distribution of calcium concentrations to higher levels, and increased the mean and median calcium concentrations. Analysis of individual adult neurons prior to and following the addition of serotonin revealed that approximately 50% of the neurons responded with an increase in calcium concentration. In contrast, there was no evidence of a serotonin-induced decrease in calcium concentration in any neurons. Since the percentage of neurons responding to serotonin in this study is very similar to the percentage that responded in previous studies on neurite outgrowth, these data support the hypothesis that an increase in intracellular calcium is a common intermediate step in the regulation of neurite outgrowth by serotonin throughout the Helisoma nervous system. PMID- 1414439 TI - Modifications of synaptosomal plasma membrane protein composition in various brain regions during aging. AB - The age-dependent modifications of synaptosomal plasma membrane protein composition in three different rat brain regions (cerebral cortex, cerebellum and striatum) at various ages (4, 12 and 24 months) were studied. The proteins were separated by gel-electrophoresis and the quantity of the different polypeptides was determined densitometrically from the stained gels. In the three brain regions examined several age-related modifications in the amount of the synaptosomal plasma membrane proteins were observed. In particular a significant decrease in the content of some synaptosomal plasma membrane proteins at 24 months of age was found. The age-related modifications in the protein composition of synaptosomal plasma membrane may cause changes in many brain functions, such as neurotransmission, ionic transport and enzyme activities. Particularly interesting is the decrease of a protein with 18 kDa mol. wt. This protein has been identified as calmodulin by immunoblotting assay. The decrease in the amount of this protein may be correlated to the impairment of several Ca(2+)-requiring processes in the aging brain. PMID- 1414440 TI - Patterns of ethanol-induced cell death in the developing nervous system of mice; neural fold states through the time of anterior neural tube closure. AB - Vital staining and routine histological analyses of mouse embryos 12 h after acute maternal ethanol administration (2.9 g/kg) illustrated that selected neuronal cell populations are killed. At the time of treatment, embryos had 5-15 somite pairs, corresponding to the developmental stages occurring in humans during the fourth week of post-fertilization; i.e. when neural folds are present and neural tube fusion begins. Affected cell populations in embryos having 6-26 somite pairs (up to the stage of anterior neuropore closure) were in discrete locations in the alar and basal plates of the rhombencephalon, in the otic placode/vesicle, and in the regions of the epibranchial placodes, olfactory placodes and trigeminal ganglion. The potential basis for the vulnerability of these cell populations to ethanol-induced cell death is discussed. Our understanding of the scope of ethanol-induced CNS damage is dependent upon further defining ethanol-sensitive cell populations at all stages of CNS development. PMID- 1414441 TI - Insulin receptor in mouse neuroblastoma cell line N18TG2: binding properties and visualization with colloidal gold. AB - Insulin function in the nervous system is still poorly understood. Possible roles as a neuromodulator and as a growth factor have been proposed (Baskin et al., 1987, Ann. Rev. Physiol. 49, 335-347). Stable cell lines may provide an appropriate experimental system for the analysis of insulin action on the various cellular components of the central nervous system. We report here a study to investigate the presence and the properties of insulin specific binding sites in the murine neuroblastoma line, N18TG2, together with insulin action on cell growth and metabolism. Also, receptor internalization has been studied. Binding experiments, carried out in standard conditions at 20 degrees C, enabled us to demonstrate that these cells bind insulin in a specific manner, thus confirming previous findings on other cell lines. Saturation curves showed the presence of two binding sites with Kd 0.3 and 9.7 nM. Competition experiments with porcine and bovine insulin showed an IC50 of 1 and 10 nM, respectively. Competition did not occur in the presence of the unrelated hormones ACTH and FSH. Dissociation experiments indicated the existence of an internalization process of the ligand receptor complex; this was confirmed by an ultrastructural study using gold conjugated insulin. As far as the insulin action in N18TG2 cells is concerned, physiological concentrations stimulate cell proliferation, whereas no stimulation of glucose uptake was observed, indicating that insulin action in these cells is not mediated by general metabolic effects. On the basis of these data, N18TG2 line appears to be a very suitable model for further studies of the neuronal type insulin receptors, and possibly insulin specific action on the nervous system. PMID- 1414442 TI - The extracellular matrix of cerebral gray matter: Golgi's pericellular net and Nissl's nervosen grau revisited. AB - Glial hyaluronate-binding protein (GHAP) and a large aggregating chondroitin sulfate proteoglycan (Ag-Pg) similar to a fibroblast proteoglycan (versican) were localized in bovine, dog and cat central nervous system (CNS) gray matter by indirect immunofluorescence. The distribution of the two hyaluronate-binding proteins was identical with that of hyaluronate, an extracellular glycosaminoglycan. All substances formed a finely reticulated mesh in the neuropil with a condensation of the stain around large neurons. It is concluded that in gray matter, as in white matter, the extracellular matrix (ECM) contains hyaluronate-protein aggregates. We suggest that the hyaluronate-protein aggregates correspond to the pericellular network first described by Golgi. PMID- 1414443 TI - Effects of pentylenetetrazol-induced seizures on dopamine and norepinephrine levels and on glucose utilization in various brain regions of the developing rat. AB - Levels of dopamine and norepinephrine were measured in seven brain areas after 60 min of sustained seizure activity induced by intraperitoneal repetitive timed administrations of pentylenetetrazol in rats at 10, 14, 17 and 21 days of postnatal life. The tissue levels of norepinephrine were markedly reduced in the majority of brain structures, except for striatum at 10 and 14 days. Conversely, dopamine concentrations increased in many areas and at various ages, except in cerebral cortex at 10 and 14 days and in midbrain between 14 and 21 days. PTZ seizures induced marked increases over control levels in the rates of glucose utilization, measured by the quantitative autoradiographic [14C]2-deoxyglucose method, in all dopamine- and norepinephrine-innervated areas studied at 10 and 14 days, except in cerebellar cortex at both ages and in frontal cortex and anteroventral thalamus at 14 days. At 17 and 21 days, glucose utilization remained increased over control levels in some areas, mainly in catecholaminergic cell groupings such as substantia nigra, ventral tegmental area and locus coeruleus, but was significantly reduced in cortex, caudate nucleus and thalamus, and similar to control rates in other regions. The present results suggest that pentylenetetrazol-induced seizures lead to a simultaneous increase in functional activity of norepinephrine neurons and an inhibition of dopaminergic-mediated neurons. They also confirm the maturation of connections, of metabolic activity and of neurotransmitter interaction within the brain, occurring mainly during the third week of postnatal life, paralleled by an increased selective vulnerability of some regions to this kind of insult. PMID- 1414444 TI - Culture of dorsal root ganglion neurons from aged rats: effects of acetyl-L carnitine and NGF. AB - In vitro neuronal preparations are used to study the action mechanism of substances which are active in normal and pathological brain aging. One major concern with in vitro assays is that the use of embryonic or adult neurons may hamper an appreciation of the relevance of these substances on aged nervous tissue. In the present study for the first time cultures of aged dorsal root ganglia from 24-months-old rats were maintained in vitro up to 2 weeks. This model was used to investigate the neurotrophic/neuroprotective action of nerve growth factor and acetyl-L-carnitine. A large population of aged dorsal root ganglia neurons was responsive to nerve growth factor (100 ng/ml). Nerve growth factor induced an increase of initial rate of axonal regeneration and influenced the survival time of these neurons. Acetyl-L-carnitine (250 microM) did not affect the axonal regeneration but substantially attenuated the rate of neuronal mortality. A significant difference was evident between the acetyl-L-carnitine treated and the untreated neurons from the first cell counting (day 3 in culture). After 2 weeks the number of aged neurons treated with acetyl-L carnitine was almost double that of the controls. The effects of acetyl-L carnitine on aged DRG neurons potentially explain the positive effects in clinical and in vivo experimental studies. PMID- 1414445 TI - Serotoninergic reinnervation of regenerating tentacular sensory organs in a pulmonate snail, Cryptomphalus aspersa. AB - Several ontogenetic studies performed in different species suggest a developmental role for 5-HT neurons. The 5-HT system interconnecting the CNS and the tentacular sensory organs in pulmonates is a suitable model for studying the postulated developmental role of 5-HT neurons. In this paper we describe the behavior of the 5-HT fibers during the early stages of blastema reinnervation, primordium formation and differentiation of regenerating tentacular sensory organs in the pulmonate snail Cryptomphalus aspersa. Our results show that the regeneration process allows the development of a normal pattern of 5-HT innervation of the regenerated sensory organs and suggest that 5-HT could be involved in reciprocal developmental interactions with regenerating tentacular tissues. PMID- 1414447 TI - Factors associated with regular aerobic exercise in an elderly population. AB - BACKGROUND: Little is known regarding the characteristics of elderly persons who do not regularly exercise. This lack of knowledge limits the design and marketing of exercise programs to persons who could benefit from regular exercise. METHODS: We compared characteristics of regular exercisers and nonexercisers among 561 randomly selected persons aged 65 years and older who were enrollees of a health maintenance organization. Baseline data were obtained on sociodemographics, health attitudes, and medical conditions. RESULTS: Of the 561 persons studied, 192 (34 percent) were regular exercisers. Exercisers were slightly younger than nonexercisers and reported more positive health perceptions. Nonexercisers tended to report lower incomes and lower educational levels than did exercisers. Exercisers were less likely to report hypertension, arthritis, or two or more of the following medical conditions: heart disease, hypertension, arthritis, and emphysema (odds ratio 0.49; confidence interval 0.28 to 0.86). Sex differences were present. In logistic regression analysis, higher reported income, better perception of current health, and fewer than two medical conditions were associated with regular exercise status. CONCLUSIONS: Specific characteristics are present in persons who regularly exercise compared with those who do not. These findings may prove useful in understanding the dynamics of exercise behavior in this age group and in designing exercise interventions for this population. PMID- 1414446 TI - The effective diagnosis and treatment of hypertension by the primary care physician: impact of ambulatory blood pressure monitoring. AB - BACKGROUND: Ambulatory blood pressure monitoring (ABPM) has been described as an effective method for the diagnosis and formulation of the treatment of hypertension by the primary care physician. METHODS: Sixty patients selected from a suburban private primary care practice participated in a study that compared measurements of office blood pressures using a mercury sphygmomanometer with the same pressures recorded by ABPM. RESULTS: Blood pressures and blood pressure loads measured by ABPM were significantly lower than blood pressures and pressure loads recorded in the office setting. CONCLUSIONS: Blood pressure recorded by ABPM differed from the same measurements made by office or casual sphygmomanometry. Use of ABPM changed diagnosis or treatment of hypertension in borderline and antihypertensive drug-treated patients. Ambulatory blood pressure monitoring is a useful tool for the diagnosis and treatment of hypertension by the primary care physician. It can be used to identify white-coat hypertension in various patient populations. PMID- 1414448 TI - Patient outcomes in hospital-based respite: a study of potential risks and benefits. AB - BACKGROUND: Primary care physicians provide increasing care for elderly patients with chronic disabilities. To maintain these individuals in the community, families and other caregivers are supplying more intensive support in the home. Services, such as short-term respite care, can relieve the caregiver burden and allow the patient to continue community living. Whether hospital-based respite can be an effective option for patients is unclear. METHODS: To determine the patient outcomes in hospital-based respite, 15 elderly male respite patients (mean age 71 years) were matched and compared during a 6-month period with 14 elderly acute care control patients and 16 community-based elderly control patients who were chronically ill and were enrolled in a hospital-based home-care program. RESULTS: The average respite stay was 15 days. The respite group did not experience increased risk of mortality or iatrogenesis. Benefits at 6 months included fewer admissions for acute medical care for the respite group (P less than 0.05). Total number of hospital days was equivalent for the respite group and community-based control patients and was fewer than that for the acute care group. CONCLUSION: The results do not indicate any harm and argue that a slight benefit is associated with hospital-based respite for chronically ill older adults. Because of potential complications that can develop for chronically ill geriatric patients, a hospital setting for respite can be a viable respite alternative. A valid concern for physicians, however, remains the potential danger of a greater rate of iatrogenic illness and expectation of more aggressive care based on a tertiary care model. PMID- 1414449 TI - Intervention to increase seat belt use at a primary care center. AB - BACKGROUND: Increasing seat belt use represents an ideal opportunity for preventive health care in family practice. Little evidence exists, however, that primary care physicians can increase safety belt use. METHODS: Three hundred twenty-six patients seen in a rural primary care center were randomized to either a control or intervention group. Before their health care examination, patients completed a short questionnaire concerning seat belt use and then viewed a 6 minute videotape explaining reasons to wear seat belts (intervention) or espousing general preventive health care guidelines with no mention of seat belts (control). In 6 months the questionnaire was again administered with no further intervention. RESULTS: Two hundred forty-three (74.5 percent) patients completed both baseline and 6-month questionnaires. Seat belt use increased significantly from baseline to 6 months for the intervention (22 to 37.3 percent, P = 0.00052) and control (20 to 33.6 percent, P = 0.00085) groups; however, the difference between the increase in the intervention (37.3 percent) and control (33.6 percent) groups at 6 months was insignificant (P = 0.641). The most common reasons for not using seat belts were forgetfulness (40.3 percent), fear of being trapped (26.7 percent), and lack of comfort (21.8 percent). CONCLUSIONS: Seat belt use increased in this study, although the intervention videotape was no better than the control videotape at increasing restraint use. This increase in use supports office-based intervention to improve seat belt use, but further research is needed to clarify the mechanism and extent of change possible. PMID- 1414450 TI - Alpha 1-antitrypsin-deficiency-related emphysema. AB - BACKGROUND: A congenital cause of emphysema resulting from alpha 1-antitrypsin (A1AT) deficiency affects 1 in 2500 individuals and could account for emphysema in 2 percent of all persons with emphysema. Individuals aged 30 to 45 years with chronic shortness of breath and coughing could have A1AT deficiency. METHODS: Using the key words "alpha 1-antitrypsin deficiency," "chronic obstructive pulmonary disease," and "emphysema," the MEDLINE files were searched from 1985 to the present. Data from articles published before 1985 were accessed from cross reference of the recent articles. RESULTS AND CONCLUSIONS: Unlike smoker's emphysema, A1AT deficiency is panacinar, appears in middle-aged patients, and is more severe at the lung bases. Chronic bronchitis, mucous hypersecretion, and liver disease, as well as a family history of emphysema, are associated conditions. Clinical management includes the avoidance of smoking and atmospheric pollution. Also available is purified, functional human A1AT in quantities large enough for intravenous replacement or augmentation therapy. Future treatment for the disease includes synthetic elastase inhibitors and an aerosolized formulation of A1AT, which is currently under investigation. PMID- 1414451 TI - Premature labor, Part I: Risk assessment, etiologic factors, and diagnosis. AB - BACKGROUND: This paper, the first of a two-part series on premature labor, reviews the recent literature on the causes of and risk factors for preterm labor and methods of diagnosis. METHODS: A review of the literature on risk determination and diagnosis of preterm labor was conducted by searching MEDLINE files from 1983 to the present, using the key terms "preterm labor," "premature labor," "preterm labor and infection," and "uterine monitoring." Additional references were accessed by cross-referencing the bibliographies of the articles obtained through this search. RESULTS AND CONCLUSIONS: Risk factors for preterm labor, which include items related to the pregnant woman's demographic characteristics, history, daily habits, and current pregnancy, have been combined into scoring systems commonly used by clinicians and researchers to single out women at risk for preterm delivery. When such systems are tested in obstetric populations, results show variable success in predicting preterm labor or birth. These inconsistent results could be due, in part, to important factors that have often been omitted from scoring systems, such as chemical abuse, poor nutrition, little social support, demanding work, multiple sexual partners, past or current sexually transmitted diseases, and other gynecologic infections. Women who are considered high risk for preterm labor can benefit from participating in preterm birth prevention programs that incorporate home monitoring, patient education regarding the signs and symptoms of preterm labor, frequent contacts with health professionals, and cervical examinations. PMID- 1414452 TI - Improving marital relationships: strategies for the family physician. AB - BACKGROUND: Marital conflict and divorce are prevalent in our society, and patients frequently ask family physicians to assist them with marital difficulties. These difficulties are often associated with a decline in health, resulting in additional stress to the marital unit. METHODS: A MEDLINE search was undertaken using the key words "family medicine," "marital therapy," "marital counseling," "brief psychotherapy," and "short-term psychotherapy." The bibliographies of generated articles were searched for additional references. The authors used the resources of their individual behavioral science libraries, as well as their clinical experiences. RESULTS AND CONCLUSIONS: With adequate training, many family physicians can include marital counseling skills in their clinical repertoires. Family life cycle theory provides a framework for understanding the common stresses of marital life and also guides the family physician in recommending strategies to improve marital satisfaction. The physician's role is twofold: (1) to identify couples in crisis, and (2) to provide preventive strategies geared to assist couples in achieving pre-crisis equilibrium or higher levels of functioning. For physicians whose practices do not include marital counseling, an understanding of the basic techniques can be beneficial in effectively referring appropriate couples for marital therapy. PMID- 1414453 TI - First name or last name: which do patients prefer? AB - BACKGROUND: Opinions are frequently expressed in the medical literature whether patients should be addressed by their first or last names, but few supportive data are available. Our objective was to determine the preferences of a sample of ambulatory patients to guide physicians and other professionals in addressing their patients appropriately. METHODS: Three hundred seventy-five patients in a variety of ambulatory settings were asked how they wished to be addressed by physicians in various contexts. RESULTS: When meeting a physician for the first time, 45 percent of the respondents wanted to be called by their first names, 29 percent preferred last names, and 26 percent found either approach acceptable. When being addressed by a physician with whom they were already well acquainted, 78 percent favored given names, and only 6 percent chose surnames. Preferences varied little with age of the patient or with age or sex of the physician. CONCLUSIONS: These data indicate that one cannot predict reliably how a new patient will prefer to be addressed but that the great majority of established patients will want to be called by their first names. PMID- 1414454 TI - A fatal case of toxic shock associated with group A streptococcal cellulitis. PMID- 1414455 TI - Fetal tachycardia associated with maternal use of pseudoephedrine, an over-the counter oral decongestant. PMID- 1414456 TI - Hyperparathyroidism. PMID- 1414457 TI - Urinary gnathostomiasis in a Laotian refugee. PMID- 1414458 TI - Reflections in family practice. The last call. PMID- 1414459 TI - Primary medical care: a riddle and a parable. PMID- 1414460 TI - A "new" standard for the diagnosis of mild hypertension? PMID- 1414461 TI - Depression after childbirth. PMID- 1414462 TI - Measurers of clinical effectiveness. PMID- 1414463 TI - Health promotion for the nursing home patient. PMID- 1414464 TI - Intrapleural application of natural IFN alpha in breast cancer patients with pleural carcinomatosis. Monitoring of immunotherapy by assaying serum interferon levels. AB - For resistant local recurrence, e.g. in breast cancer, or metastatic spread, local infiltration of IFN may be an interesting new approach. The aim of this study was to find out if intrapleurally administered interferon, in breast cancer patients with pleural carcinomatosis, can cause measurable serum concentrations and how soon after administration. Serum IFN concentrations were compared with those in the pleural fluid, and correlated with the presence of malignant cells in the pleural fluid. To uncover possible rhythmicity of serum interferon levels and its relationship to the timing of therapy, natural leukocyte interferon was administered intrapleurally at 10 a.m. Data on pharmacokinetics were obtained from blood samples drawn at -2, 0, 2, 8, 14, 22 and 46 h during the course of treatment. In contrast to our previous observations in healthy volunteers, levels of serum IFN before therapy had no circadian rhythmicity. Daily pharmacokinetic profile of individual patients on interferon therapy has shown that serum IFN peaks 8 h after intrapleurally administered IFN alpha. The peak depended on frequency and number of applied doses. During treatment with IFN alpha, malignant cells degenerated and finally disappeared from pleural fluid. At the same time reactive cells appeared. This effect is rather uniformly observed, but varies in degree. The number of patients is too small, however, to permit conclusions in regard to correlation of this clinical effect and the levels of serum IFN alpha. PMID- 1414465 TI - Cerebrospinal fluid T cell receptor gamma/delta+ lymphocyte subsets in patient with AIDS-dementia complex. AB - A subset of peripheral T cells, whose physiological function is little known, expresses a distinct CD3-associated receptor composed of gamma and delta chains. We used two monoclonal antibodies to characterize the TcR gamma/delta lymphocytes (TcR delta 1+) and their fraction (TcS delta 1+) in peripheral blood and cerebrospinal fluid of patients affected by AIDS dementia complex (ADC). Thirty patients with ADC and a control group of twenty individuals with other non inflammatory neurological diseases (OND) were recruited. Our results demonstrate that the TcR gamma/delta cells were also present in cerebrospinal fluid of ADC patients, but we did not find any statistical difference between the two groups. PMID- 1414466 TI - In vivo and in vitro macrophage activation induced by IFN gamma spontaneously released by spleen cells from tumor bearing mice. AB - Peritoneal macrophages obtained from Lewis Lung carcinoma (3LL) tumor bearing mice release high amounts of soluble factors such as C3,H2O2 and lysosomal enzymes but fail to exert cytotoxic activity on tumor cells. In the present work we show that they acquire this property and become fully activated after in vitro incubation with supernatants derived from cultures of splenocytes from tumor bearing syngeneic mice. The presence of IFN gamma in the above supernatants was detected by immunoblotting analysis and by bioassay. The role played by IFN gamma in macrophage activation was investigated. PMID- 1414467 TI - [Angioplasty of the arteries of the aorto-iliac region]. AB - Percutaneous transluminal angioplasty (PTA) of the aorto-iliac arteries was performed in 92 patients with atherosclerotic lesions. The initial success was 87.8% and the late one was 69.4%. The late results were evaluated objectively in 58 patients, 36 of which were studied by angiography and the remaining by Doppler. There were 6.6% of complications, in 2.8% of which surgery was performed. There was no mortality. The good initial and late results and the low morbility suggest that PTA is a good revascularization procedure. The best results were obtained in symptomatic patients with a short and significant stenosis or occlusion. PMID- 1414468 TI - [Angioplasty of the arteries of the femoro-popliteal region]. AB - Percutaneous transluminal angioplasty (PTA) of the femuro-popliteal arteries with atherosclerotic lesions, was performed in 66 patients. There was an initial clinical success in 80.3% and a late one in 60.7%. Better results were obtained when there was good distal circulation, and the differences were significant. There was no mortality. These results show that PTA is an useful procedure in the treatment of obstructive lesions of femuro popliteal arteries. PMID- 1414469 TI - [Systemic granulomatous disease, of the sarcoid type, caused by inhalation of titanium dioxide. Anatomo-clinical and experimental study]. AB - Epithelioid granulomas, sarcoid type, are reported in four workers exposed to the inhalation of titanium dioxide dust. The granulomas were observed in the lungs, associated with respiratory insufficiency leading to death, in the hilum lymph nodes and liver. Diagnosis was done after a search of the occupational background of the patients followed by chemical and histochemical identification of the inhaled dusts within the lesions (morin and chromotropic acid methods and atomic absortion spectrophotometry) and experimental production of the disease in guinea pigs. The harmful effects of titanium are not restricted to its dioxide, or to the inhalatory route. Different types of ceramic used in human implants and prostheses and the textile and aerospace industries use titanium. PMID- 1414470 TI - [Current therapy of rheumatoid arthritis and future perspectives]. PMID- 1414471 TI - [Sarcoidosis as a cause of febrile++ syndrome of unknown origin. Retrospective study of 8 cases]. AB - The authors report the results of a retrospective study of patients admitted to the Department of Infectious Diseases of Santa Maria Hospital with the diagnosis of sarcoidosis, from June 1982 to August 1991. Seven out of eight patients, were admitted due to fever of unknown origin. The results are discussed and the literature on sarcoidosis is also reviewed. PMID- 1414472 TI - [Organ transplantation and the beginning of programs of liver transplantation in Portugal]. PMID- 1414473 TI - [Intravascular surgery--from the initial euphoria to the current pondering, the story repeats itself]. PMID- 1414474 TI - [Psychosocial impact on children with mucopolysaccharidosis]. AB - The authors present a global valuation of the psychological repercussion of the child produced by a cronic and genetic disease like mucopolissacaridosis. The A. describe also those repercussion on the family and the school of the child. Finally they point the actual therapeutic support of the child and his family and remarks the need or pedopsychiatric management. PMID- 1414475 TI - [Adenocarcinoma of the colon disclosed by endocarditis caused by Streptococcus bovis]. AB - The association of Streptococcus bovis endocarditis with colonic neoplasms has been well documented. We describe a patient in whom the finding of a Str. bovis endocarditis stimulated investigation which resulted in the diagnosis and surgical treatment of an adenocarcinoma of the colon. PMID- 1414476 TI - [Dyskinesia induced by isolated and low-dose bromocriptine]. PMID- 1414477 TI - X-linked hypophosphatemic rickets: a study (with literature review) of linear growth response to calcitriol and phosphate therapy. AB - Not all children with X-linked hypophosphatemia (XLH) have demonstrated improved linear growth with calcitriol [1,25-(OH)2D3] and inorganic phosphate (Pi) therapy. To assess which factors are associated with a favorable growth response during this treatment, we retrospectively compared demographics and biochemical parameters of bone metabolism to the linear growth patterns of 20 children with XLH who were prepubertal and had not required osteotomy. A total of 15 patients had family histories consistent with XLH; 5 appeared to be sporadic cases. During 3 years of therapy, the growth velocities of 12 patients had been at or above the mean for age (good growers) and those of 8 patients had been below the mean (poor growers). Data from the two groups were contrasted. We found no difference between the good growers and poor growers before or after the 3 year period of therapy in mean age, dietary calcium, calcitriol dose or compliance, or Pi dose or compliance. Both groups increased their mean fasting serum Pi levels with treatment. The TmP/GFR (mean +/- SEM) of the good growers improved with therapy (1.9 +/- 0.2 to 2.6 +/- 0.2 mg/dl, p = 0.01), and their posttreatment value was higher compared to that of the poor growers (2.6 +/- 0.1 versus 2.2 +/- 0.1 mg/dl, p = 0.02). However, their enhanced TmP/GFR was not associated with a reduction in serum iPTH levels (before, 693 +/- 50; after, 688 +/- 76 pg/ml; p = 0.9). The Z test for binomial proportions showed that the group that grew well contained a disproportionate number of girls (10 of 12, p = 0.04). Our findings suggest that calcitriol may exert a direct effect on the renal tubule to improve Pi reclamation in XLH. The observation that heterozygous girls appear to respond better than hemizygous boys to calcitriol and Pi therapy provides evidence for a gene dosage effect in the expression of this X-linked dominant disorder. PMID- 1414478 TI - Longitudinal effect of tiludronate on bone mineral density, resonant frequency, and strength in monkeys. AB - The effect of Tiludronate on bone was studied in 72 growing monkeys (Papio papio), 36 males and 36 females, aged 4-7 years. They were randomly allocated into four groups (18 animals per group, 9 males and 9 females): group I, controls; group II, 10 mg/kg/day; group III, 20 mg/kg/day; and group IV, 40 mg/kg/day of Tiludronate. A total of 12 animals (6 males and 6 females) in each group were sacrificed at the end of treatment (1 year) and 6 animals (3 males and 3 females) per group 1 year later. Bone mineral density (BMD) was measured by dual-photon absorptiometry. Biomechanical properties were evaluated by an impact torsion test and by resonant frequency analysis. Bone mineral measurements indicated that at the end of 1 year of treatment BMD was significantly higher, especially at the distal epiphysis of the radius, than in controls. No significant differences between groups were found in BMD 1 year after stopping treatment. Biomechanical analyses indicated that torsional stiffness increased after treatment. No differences between groups were found 1 year after stopping treatment. Results of resonant frequencies indicated an increased calculated transversal stiffness after treatment and 1 year later and an increased buckling strength 1 year after stopping treatment. In conclusion, the results on the effect of Tiludronate in growing monkeys indicate a profound effect of this drug on bone density and biomechanical properties. The biomechanical results indicate that this drug is safe, with conservation of bone strength despite a change in intrinsic mechanical properties of the bone. PMID- 1414479 TI - Endurance training associated with slightly lowered serum estradiol levels decreases mineral density of canine skeleton. AB - The effects of long-term running exercise were studied in 20 beagle dogs. A total of 10 dogs ran from the age of 15 weeks to the age of 70 weeks in a progressive program for up to 40 km/day. A total of 10 sister dogs spent the study period in individual cages. When the dogs were 70 weeks old, bone mineral density of the vertebrae, hip, and radius was analyzed by dual-energy x-ray absorptiometry (DEXA; Lunar) and the vertebrae were also assessed by quantitative computed tomography (QCT; Siemens DR 1). Mineral density was lower in the running dogs than in the controls. The difference was greatest in the spine in the QCT analysis. Blood chemistry analyses revealed that the metabolism of the bone was significantly accelerated. The estradiol levels showed the trend to be reduced in the running group. The beneficial effect of exercise on mineral density has been shown in many earlier studies. However, in this study we demonstrate the possibility of adverse effects of long-term exercise on bone tissue. The change was associated with a decrease of serum estradiol level. PMID- 1414480 TI - Age-related decrements in bone mineral density in women over 65. AB - Age-related changes in bone density contribute to the risk of fractures. To describe the relationship between age and bone mass in elderly women, we studied a large cohort of women over age 65 years who were recruited from population based lists in four cities in the United States. Bone density in g/cm2 was measured by single-photon absorptiometry (SPA) and dual x-ray absorptiometry (DXA) at the distal and proximal radius, the calcaneus, the lumbar spine, and the proximal femur. Centralized data collection was used to control data quality and consistency. We found a strong inverse relationship between bone density and age for most sites. Decrements in bone density between women aged 65-69 years and women 85 years and older exceeded 16% in all regions except the spine, where the difference between the two age groups was 6%. Ward's triangle and the calcaneus exhibited the largest decrements, with 26 and 21%, respectively. The estimates of annual changes in bone mineral density by linear regression at sites other than the spine ranged from -0.82% at the femoral neck and trochanter to -1.30% at Ward's triangle. Correlations between the different regions ranged from r = 0.51 between the proximal radius and Ward's triangle to r = 0.66 between the distal radius and calcaneus. We conclude that the inverse relationship between age and bone mass measured by absorptiometry techniques in white women continues into the ninth decade of life. The relationship is strongest for bone density of Ward's triangle and the calcaneus and weakest for the spine. PMID- 1414481 TI - Axial and appendicular bone density predict fractures in older women. AB - To determine whether measurement of hip and spine bone mass by dual-energy x-ray absorptiometry (DEXA) predicts fractures in women and to compare the predictive value of DEXA with that of single-photon absorptiometry (SPA) of appendicular sites, we prospectively studied 8134 nonblack women age 65 years and older who had both DEXA and SPA measurements of bone mass. A total of 208 nonspine fractures, including 37 wrist fractures, occurred during the follow-up period, which averaged 0.7 years. The risk of fracture was inversely related to bone density at all measurement sites. After adjusting for age, the relative risks per decrease of 1 standard deviation in bone density for the occurrence of any fracture was 1.40 for measurement at the proximal femur (95% confidence interval 1.20-1.63) and 1.35 (1.15-1.58) for measurement at the spine. Results were similar for all regions of the proximal femur as well as SPA measurements at the calcaneus, distal radius, and proximal radius. None of these measurements was a significantly better predictor of fractures than the others. Furthermore, measurement of the distal radius was not a better predictor of wrist fracture (relative risk 1.64: 95% CI 1.13-2.37) than other sites, such as the lumbar spine (RR 1.56; CI 1.07-2.26), the femoral neck (RR 1.65; CI 1.12-2.41), or the calcaneus (RR 1.83; CI 1.26-2.64). We conclude that the inverse relationship between bone mass and risk of fracture in older women is similar for absorptiometric measurements made at the hip, spine, and appendicular sites. PMID- 1414482 TI - Appendicular bone mineral and a woman's lifetime risk of hip fracture. AB - Appendicular bone mass is inversely related to the risk of hip fracture in short term prospective studies, but hip fractures typically occur about 30 years after menopause. We developed a model that estimates a woman's lifetime risk of hip fracture based on measurement of radial bone mass at age 50 using short-term prospective data relating bone mass to hip fracture, the correlation between bone mass at age 50 and later years, the age-specific incidence of hip fracture and mortality, and prospective data about bone mass and mortality. We estimate that a 50-year-old white woman has a 19% lifetime risk of hip fracture if her radial bone mass is at the 10th percentile for her age and an 11% lifetime risk if her bone mass is at the 90th percentile. Improved measurement techniques that have a higher predictive value for hip fracture in short-term studies could substantially increase this gradient of lifetime risk and therefore be more clinically useful. PMID- 1414483 TI - Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss. AB - Radial bone mineral density (BMD) of 217 white women aged 22-54 years from a single rural community was evaluated in 1984 using single-photon absorptiometry. BMD was measured at a site one-third the distance from the wrist to the elbow, a site that represents predominantly cortical bone tissue. Most of these women (181; 83%) were reexamined 5 years later. The overall average 5 year radial BMD loss was -5.6%. The average rate of loss was -4.5% for women retaining positive estrogen status at follow-up (n = 108) and -7.4% for women who were in negative estrogen status at follow-up (n = 73). Baseline radial BMD measures were highly predictive of the follow-up BMD values (r = 0.80). Women with positive estrogen status and greater baseline BMD also had less BMD change. Greater baseline BMD did not predict the amount of change in women with negative estrogen status. The bone turnover markers osteocalcin and bone-specific alkaline phosphatase were significantly associated with BMD change in women with negative, but not positive estrogen status. There was no conclusive evidence of a "peak age" in the baseline and follow-up BMD measures. Based on rates of BMD change, "peak" bone mineral content appears to occur before age 25 years. Factors significantly associated with lower levels of BMD were menopause without estrogen replacement, nulliparity, smoking, and age at first pregnancy. Factors associated with more bone loss were menopause without estrogen replacement, smoking, shorter duration of oral contraceptive use, and older age. Quetelet index, muscle area, number of lost pregnancies, ever breast-feeding, or calcium intake were not associated with BMD level or its 5 year rate of loss. Physical activity and alcohol intake were not associated with BMD level or change after data were adjusted for age or estrogen status. PMID- 1414484 TI - Influence of oophorectomy on serum levels of sex steroids and bone metabolism and assessment of bone mineral density in lumbar trabecular bone by QCT-C value. AB - The present cross-sectional study was carried out to determine the influence of oophorectomy (OPX) on serum levels of sex steroids and bone metabolism, as well as bone mineral density (BMD), in OPX subjects in comparison with age- and body size-matched controls. Quantitative computed tomography (QCT) and dual-photon absorptiometry (DPA) demonstrated a remarkable reduction in BMD in OPX subjects. In particular, the QCT of the centrum of vertebral bone (QCT-C) in these subjects was no more than 69.33 +/- 3.40% (X +/- SEM) of the control value, and this parameter was much lower than the QCT integral (QCT-I) value of total lumbar vertebrae. This means that BMD decreases specifically in spongy portions after OPX. The serum level of estrone (E1) was significantly lower in OPX subjects than in controls. The hormonal action of E1 on target organs has been thought to be only one-third of that of estradiol (E2), but the marked reduction in serum E1 level seemed to be a significant cause of the reduction in BMD. The serum level of androstenedione (delta 4) significantly decreased in OPX subjects and appeared to affect bone metabolism negatively. Both bone formation and bone resorption were found to be stimulated following OPX, but the rate of bone resorption was found to be higher than that of bone formation: there was an imbalance between bone formation and bone resorption in OPX subjects. However, it was not possible to prove a relationship between Ca regulating hormone and this phenomenon. In conclusion, the QCT-C value reflects the changes in spongy vertebral BMD more sensitively than the QCT-I value or DPA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414485 TI - Activation and inhibition of protein kinase C in cultured bovine parathyroid cells: effect on the release of C-terminal fragments of parathyroid hormone. AB - The response of the parathyroid gland to low Ca2+ may be mediated in part by protein kinase C (PKC). We assessed the effect of two PKC activators, SC-9 and SC 10, and one PKC inhibitor, H-7, on Ca(2+)-regulated PTH release and degradation in primary cultures of bovine parathyroid cells. Both SC-9 and SC-10 stimulated PTH release, compared to high Ca2+ alone, in parathyroid cells incubated in high Ca2+, with maximal PTH release of at least twofold occurring at a concentration of either activator of 10 nM (p less than 0.05). We have previously shown that another PKC activator, PMA, not only enhances PTH release in the presence of high Ca2+ but suppresses low Ca(2+)-stimulated PTH secretion. In the present study, neither SC-9 nor SC-10 caused a comparable suppression of PTH release at low Ca2+. However, the PKC inhibitor, H-7 (1 microM), blocked low Ca(2+)-stimulated (compared to the low Ca2+ control) PTH secretion by approximately 50% (p less than 0.01) and did not affect high Ca2+ suppression of PTH secretion. H-7 (1 microM) was able to oppose the stimulation of PTH release by the PKC activators SC-9, SC-10, and PMA at high Ca2+ and negated the PTH release-inhibiting effect of PMA at low Ca2+. Culture medium from these experiments was subjected to reversed-phase HPLC and the eluted fractions analyzed by RIA for the presence of intact and C-terminal fragments of PTH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414486 TI - Adaptive regulation of ascorbate transport in osteoblastic cells. AB - Osteoblasts possess a concentrative L-ascorbate (vitamin C) uptake mechanism involving a Na(+)-dependent ascorbate transporter located in the plasma membrane. The transporter is specific for ascorbate and stereoselective for L-ascorbate over D-isoascorbate. The present study examined the effects of ascorbate supplementation and deprivation on the activity of this transport system. L ascorbate transport activity was determined by measuring uptake of the vitamin by ROS 17/2.8 osteosarcoma cells during 1 minute incubations with 5 microM L [14C]ascorbate. The initial rate of L-[14C]ascorbate uptake by ROS 17/2.8 cells grown for 18 h in L-ascorbate-replete medium was 89 +/- 8 nmol/g protein per minute. Following removal of L-ascorbate from the growth medium, the initial rate of uptake increased within 6 h to 126 +/- 13 nmol/g protein per minute. Conversely, the initial rate of uptake by cells grown in ascorbate-free medium decreased following the addition of L-ascorbate, but not D-isoascorbate, to the medium. The effect of ascorbate pretreatment was specific for ascorbate transport in that preincubation of cultures with L-ascorbate did not affect uptake of 2 deoxy-D-glucose. Kinetic analysis revealed that modulation of ascorbate transport arose from changes in the apparent maximum rate of transport (Vmax) without changes in the affinity of the transport system for L-ascorbate. These experiments are the first to show that ascorbate transport by osteoblastic cells responds to vitamin C deprivation and supplementation. Adaptation of transport activity to substrate availability may play an important role in the physiological regulation of intracellular ascorbate levels. PMID- 1414487 TI - Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development. AB - We examine clonal murine calvarial MC3T3-E1 cells to determine if they exhibit a developmental sequence similar to osteoblasts in bone tissue, namely, proliferation of undifferentiated osteoblast precursors followed by postmitotic expression of differentiated osteoblast phenotype. During the initial phase of developmental (days 1-9 of culture), MC3T3-E1 cells actively replicate, as evidenced by the high rates of DNA synthesis and progressive increase in cell number, but maintain a fusiform appearance, fail to express alkaline phosphatase, and do not accumulate mineralized extracellular collagenous matrix, consistent with immature osteoblasts. By day 9 the cultures display cuboidal morphology, attain confluence, and undergo growth arrest. Downregulation of replication is associated with expression of osteoblast functions, including production of alkaline phosphatase, processing of procollagens to collagens, and incremental deposition of a collagenous extracellular matrix. Mineralization of extracellular matrix, which begins approximately 16 days after culture, marks the final phase of osteoblast phenotypic development. Expression of alkaline phosphatase and mineralization is time but not density dependent. Type I collagen synthesis and collagen accumulation are uncoupled in the developing osteoblast. Although collagen synthesis and message expression peaks at day 3 in immature cells, extracellular matrix accumulation is minimal. Instead, matrix accumulates maximally after 7 days of culture as collagen biosynthesis is diminishing. Thus, extracellular matrix formation is a function of mature osteoblasts. Ascorbate and beta-glycerol phosphate are both essential for the expression of osteoblast phenotype as assessed by alkaline phosphatase and mineralization of extracellular matrix. Ascorbate does not stimulate type I collagen gene expression in MC3T3-E1 cells, but it is absolutely required for deposition of collagen in the extracellular matrix. Ascorbate also induces alkaline phosphatase activity in mature cells but not in immature cells. beta-glycerol phosphate displays synergistic actions with ascorbate to further stimulate collagen accumulation and alkaline phosphatase activity in postmitotic, differentiated osteoblast-like cells. Mineralization of mature cultures requires the presence of beta-glycerol phosphate. Thus, MC3T3-E1 cells display a time-dependent and sequential expression of osteoblast characteristics analogous to in vivo bone formation. The developmental sequence associated with MC3T3-E1 differentiation should provide a useful model to study the signals that mediate the switch between proliferation and differentiation in bone cells, as well as provide a renewable culture system to examine the molecular mechanism of osteoblast maturation and the formation of bone-like extracellular matrix. PMID- 1414488 TI - Isolation and characterization of a cDNA for osteopontin-k: a kidney cell adhesion molecule with high homology to osteopontins. AB - Screening of a bovine renal cDNA library with MAbs resulted in the isolation of a 1447 bp cDNA. This cDNA (pBk2.1) was sequenced and shown to contain an open reading frame with a putative protein of 261 amino acids, with a molecular weight of 29,573 (minute leader sequence) and a hydrophobic leader sequence of 16 amino acids. pBk2.1 was shown to share a high level of nucleic acid sequence homology over portions of its sequence to human, porcine, mouse, and rat osteopontins (40 60%). The peptide (osteopontin-k) had a potential glycosylation site (Asn-X Ser/Thr), a GRGDS receptor binding region, a high level of asparagine residues, and a high abundance of acid amino acids characteristic of osteopontin-like cell adhesion molecules. The N-terminal amino acid region of pBk2.1 (the first 82 amino acids) and 42 amino acids at the C terminus had the highest level of homology with the osteopontins at 86%. The middle portion of the peptide had greatly reduced homology, ranging from 50% (amino acids 83-174) to 12% (amino acids 175-219). There were also deletions and additions of sequence in osteopontin-k that were not found in the other osteopontins. The homologies suggest that these proteins are highly related and may be derived from a common gene by alternative splicing. A 678 bp cRNA probe constructed from pBk2.1, containing a region with low homology to the osteopontins (amino acids 183-219 with less than 20% homology, plus amino acids 220-261 and untranslated sequence), was used in northern blots and RNAse protection assays.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414489 TI - Estrogen therapy and variable-resistance weight training. PMID- 1414490 TI - Citation of Dr. Claude D. Arnaud for the 1991 William F. Neuman Award of the American Society for Bone and Mineral Research. PMID- 1414491 TI - Citation of Dr. Dean T. Yamaguchi for the 1991 Fuller Albright Award of the American Society for Bone and Mineral Research. PMID- 1414492 TI - Citation of Dr. Eduardo Slatopolsky for the 1991 Frederic C. Bartter Award of the American Society for Bone and Mineral Research. PMID- 1414493 TI - Perspective. How many women have osteoporosis? AB - Osteoporosis is widely viewed as a major public health concern, but the exact magnitude of the problem is uncertain and likely to depend on how the condition is defined. Noninvasive bone mineral measurements can be used to define a state of heightened fracture risk (osteopenia), or the ultimate clinical manifestation of fracture can be assessed (established osteoporosis). If bone mineral measurements more than 2 standard deviations below the mean of young normal women represent osteopenia, then 45% of white women aged 50 years and over have the condition at one or more sites in the hip, spine, or forearm on the basis of population-based data from Rochester, Minnesota. A smaller proportion is affected at each specific skeletal site: 32% have bone mineral values this low in the lumbar spine, 29% in either of two regions in the proximal femur, and 26% in the midradius. Although this overall estimate is substantial, some other serious chronic diseases are almost as common. More importantly, low bone mass is associated with adverse health outcomes, especially fractures. The lifetime risk of any fracture of the hip, spine, or distal forearm is almost 40% in white women and 13% in white men from age 50 years onward. If the enormous costs associated with these fractures are to be reduced, increased attention must be given to the design and implementation of control programs directed at this major health problem. PMID- 1414494 TI - Chronic adaptation of dog parathyroid function to a low-calcium-high-sodium vitamin D-deficient diet. AB - The development of secondary hyperparathyroidism was studied in relation to changes in serum ionized Ca (Ca2+), 25-OHD, and 1,25-(OH)2D concentrations in six dogs maintained on a low-Ca (0.05%), high-Na (1.6%), and vitamin D-deficient diet for 91 weeks. Blood samples and evaluations of the parathyroid function were obtained before and after 3, 12, 24, 36, and 91 weeks of diet. Serum iPTH was measured by an intact hormone (I) and a carboxy-terminal (C) assay. The sigmoidal relationship between ionized Ca and iPTH values was evaluated mathematically. Results are means +/- SD. Statistically significant changes over a time period were evaluated by an ANOVA for repeated measurements. Over the first 3 weeks, serum Ca2+, 25-OHD, and 1,25-(OH)2D did not change but stimulated I-iPTH increased 84.3 +/- 39.9% (p less than 0.005) and C-iPTH only 25.3 +/- 12.2% (p less than 0.01), a significant difference (p less than 0.02). The increase in stimulated I-iPTH reached 487.4 +/- 139.6% (p less than 0.0001) and 418.4 +/- 76.9% (p less than 0.0001) for C-iPTH by the end of the study. Similar significant increases were seen in basal and nonsuppressible iPTH at or after week 12.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414495 TI - The calcium oxalate crystal growth inhibitor protein produced by mouse kidney cortical cells in culture is osteopontin. AB - Urine contains proteins that inhibit the growth of calcium oxalate (CaOx) crystals and may prevent the formation of kidney stones. We have identified a potent crystal growth inhibitor in the conditioned media from primary cultures of mouse kidney cortical cells. Conditioned media, incubated with the kidney cells for 6-72 h, was assayed for crystal growth inhibition; inhibitory activity increased 15-fold by 24 h. Inhibitory activity was purified from serum-free media containing proteinase inhibitors using anion-exchange and gel-filtration chromatography. A single band of molecular weight 80,000 daltons was seen after SDS-polyacrylamide gel electrophoresis. The sequence of the N-terminal 21 amino acids of this protein matched that of osteopontin (OP), a phosphoprotein initially isolated from bone matrix. Antisera raised to fusion proteins produced by plasmids containing the N-terminal or C-terminal portions of OP cDNA also cross-reacted with the protein purified from cell culture media on western blots. The effect of the purified protein on the growth of CaOx crystals was measured using a constant composition assay. A 50% inhibition of growth occurred at a protein concentration of 0.85 micrograms/ml, and the dissociation constant of the protein with respect to CaOx crystal was 3.7 x 10(-8) M. The concentration of OP in mouse urine, measured using antibodies raised to the purified protein, was approximately 8 micrograms/ml. We conclude that OP is synthesized by kidney cortical tubule cells and functions as a crystal growth inhibitory protein in urine. PMID- 1414496 TI - Is heritability a risk factor for postmenopausal osteoporosis? AB - We investigated heritability as a risk factor for the development of osteoporosis in two randomly selected populations of postmenopausal women and their premenopausal daughters. We determined the familial resemblance in bone mass at three sites; the distal forearm, lumbar spine, and proximal femur, premenopausally and with increasing maternal postmenopausal age. We also examined the bone mass of daughters in relation to mothers with and without osteoporotic fractures. Peak bone mass among premenopausal siblings was significantly correlated at all sites (r = 0.30-0.42, p less than 0.001). The same levels of resemblance were found between early postmenopausal mothers and premenopausal daughters. There was no significant difference in bone mass at any skeletal site between daughters of women with either peripheral or spinal fractures and daughters of women without fractures. We also examined familial resemblance with four biochemical markers of bone turnover (fasting urinary calcium and hydroxyproline, both corrected for creatinine, serum alkaline phosphatase, and plasma bone Gla protein). A generally significant resemblance were seen in premenopausal siblings (r = 0.25-0.39, hydroxyproline NS), but not between premenopausal daughters and postmenopausal mothers. We conclude that peak bone mass is hereditary in the distal forearm, lumbar spine, and proximal femur, but the mother-daughter resemblance explains only about 16% of the variability in daughters' bone mass. Furthermore, daughters of women with a moderate state of osteoporotic fractures are not substantially at an increased risk of having a low peak bone mass compared to the daughters of women without fractures. PMID- 1414497 TI - Genetic expression of extracellular matrix proteins correlates with histologic changes during fracture repair. AB - We characterized gene expression in the reparative callus that formed after fracture of the rat femur. The callus was divided into regions of bone formation (hard callus) and cartilage formation (soft callus), and gene expression was examined separately in each region. Expression of extracellular matrix protein genes varied with the progression of repair and differed between hard and soft calluses. Messenger ribonucleic acids (mRNAs) for osteonectin, alkaline phosphatase, and type I procollagen were detected in the hard callus at maximal levels during endochondral ossification and bone remodeling (day 15) and at 50% maximal levels during intramembranous bone formation (day 7). Messenger RNAs for these proteins in the soft callus were detected at low levels during chondrogenesis (day 9) but increased to 80% of maximal levels with chondrocyte hypertrophy and mineralization of the cartilage matrix (day 13). Messenger RNAs for type II procollagen and proteoglycan core protein were detected at maximal levels in the soft callus during chondrogenesis (day 9). Osteocalcin gene expression was detected in the hard callus during endochondral ossification and remodeling but not during intramembranous bone formation or at any time in the soft callus. Osteonectin mRNA was detected in both the hard and soft callus throughout the entire course of fracture repair. Expression of cartilage and bone related genes correlated with the temporal sequence of histologic changes, suggesting transcriptional regulation of gene expression during repair. Differences in gene expression between hard and soft callus and in each of these regions as repair progressed suggest local regulation of gene expression during cell differentiation and matrix synthesis. PMID- 1414498 TI - Responsiveness to 1,25-dihydroxyvitamin D3 is reduced in lymphocytes from osteoporotic women. AB - The purpose of this work was to test the hypothesis that reduced responsiveness of target organs to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is associated with osteoporosis. Peripheral blood mononuclear (PBM) cells have been previously shown to be a valid model for the action of 1,25(OH)2D3 on its classic target organs in various pathologic and physiologic situations. The responsiveness of lymphocytes to the hormone can be assessed by the extent of inhibition it exerts on the proliferative response to mitogenic lectins. A group of 39 postmenopausal women, at least 10 years after the menopause, participated in the study. Osteoporosis, defined as the presence of at least one nontraumatic vertebral crush fracture, was diagnosed in 19 subjects. Mitogenesis of PBM cells stimulated by phytohemagglutinin and cultured for 72 h in the presence or absence of 1,25 (OH)2D3 (0.03-1 nmol/liter) was assessed by [3H]thymidine incorporation during a 4 h pulse. The maximal inhibitory effect of 1,25-(OH)2D3 at saturating concentration (1 nM/liter) was 74.6 +/- 2.8% (mean +/- SEM) for normal compared to 65.3 +/- 2.9% for osteoporotic women (P = 0.015). The geometric mean of the ED50 values of 1,25-(OH)2D3 was 60% higher in the osteoporotic than in the normal group (P = 0.035). Our data are consistent with the notion that reduced responsiveness of target organs to 1,25-(OH)2D3 is associated with osteoporosis. PMID- 1414499 TI - Site-matched calcaneal measurements of broad-band ultrasound attenuation and single X-ray absorptiometry: do they measure different skeletal properties? AB - Because of the differences in the interactions of ultrasound and x-ray waves with bone, quantitative ultrasound (QUS) techniques may yield information about skeletal status not accessible by regular bone densitometry (BD) techniques. However, relatively strong correlations have been reported between broad-band ultrasound attenuation (BUA) and several x-ray-based BD methods. We assessed the precision and association of single x-ray absorptiometry (SXA) and BUA of the calcaneus. We examined both BUA and SXA at the calcaneus using special software for matching the regions of interest. An algorithm was derived and applied to correct the observed correlation coefficients for the attenuation effect caused by the precision errors for BUA and SXA. In a group of 33 volunteers covering a wide range of age and calcaneal bone mineral densities, the site-matched and precision-adjusted correlation coefficient between BUA and SXA was r = 0.58, with a standard error of the estimate (SEE) of 14.41 dB/MHz, or 17.08%. For the subgroup of 25 women the correlation was stronger, with r = 0.72 and SEE = 11.53 dB/MHz, or 14.33%. SXA precision was 0.79% for the regular region of interest (ROI) and 1.22% for the site-matched ROI. BUA precision was 2.76% for the entire subject group and 1.63% for women of age 40 or older. The observed correlation coefficient between ultrasound and x-ray based techniques of the order of 0.7 is significant, but it leaves about 50% of the variability unexplained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414500 TI - Assessment of spinal and femoral bone density by dual X-ray absorptiometry: comparison of lunar and hologic instruments. AB - Clinical application of techniques for assessing bone mineral density (BMD) requires accurate and precise measurements that can be related to clearly defined normal ranges. In this study we investigated the clinical interpretation of BMD values in a group of individuals measured on the same day with two different dual energy x-ray densitometers (Lunar DPX and Hologic QDR 1000). The BMD results were analyzed as absolute values in g/cm2 and with respect to young and age-specific normals as defined by each manufacturer. Absolute BMD values measured by the two instruments were highly correlated (lumbar spine r = 0.98, femoral neck r = 0.95; p less than 0.0001). In the lumbar spine, the two instruments assigned almost identical values when expressed as a percentage of age-matched values and as a percentage of young normals, despite a small but systematic difference between the values assigned for the latter index. In the femoral neck, however, there were significant differences in assignments between instruments, expressed both as a percentage of young normal (mean difference 6.2%) and with respect to age matched values (mean difference 3.3%). In particular, in premenopausal subjects femoral neck values with the Hologic instrument were assigned significantly lower values. This study shows effective comparability between these two instruments for absolute and relative values for the lumbar spine, as well as for absolute values at the femoral neck, but important differences for normality assignments at the femoral neck. These latter differences may produce bias in the "diagnosis" of femoral neck osteoporosis and may have important implications for clinical decision making.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414501 TI - Effects of deflazacort on aspects of bone formation in cultures of intact calvariae and osteoblast-enriched cells. AB - Deflazacort, a synthetic glucocorticoid reported to have bone-sparing properties in vivo, and cortisol were compared for their effects on bone formation in vitro. Deflazacort and cortisol were studied for their effects on DNA and collagen synthesis in cultures of intact fetal rat calvariae and of osteoblast-enriched (Ob) cells from 21- to 22-day-old fetal rat parietal bone. Both steroids were also examined for their effects on skeletal insulin-like growth factor (IGF) I production, which is decreased by cortisol and appears relevant to its mode of action. After 24 h of culture, deflazacort and cortisol had limited effects on the parameters studied, although cortisol at 100 nM decreased [3H]proline incorporation into collagen in intact calvariae. In contrast, after 72 h deflazacort and cortisol at 1-100 nM inhibited the incorporation of [3H]thymidine into DNA and at 100 nM decreased the incorporation of [3H]proline into collagen and noncollagen protein in intact calvariae. Deflazacort and cortisol at 10-1000 nM decreased calvarial collagen degradation to a similar extent. Both steroids had a similar activity, and at 100 nM for 72 h they decreased IGF-I production by calvariae; however, cortisol at 10 nM was somewhat more effective than deflazacort in decreasing IGF-I levels. Deflazacort and cortisol had analogous effects in Ob cell cultures. After 24 h of treatment, deflazacort at 100-1000 nM and cortisol at 10-1000 nM decreased the labeling of DNA, and both steroids at 100-1000 nM caused a similar decrease in [3H]proline incorporation into collagen in Ob cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414503 TI - Demonstration of sodium/calcium exchange in rodent osteoblasts. AB - Based on the inhibition of stimulated Ca release from cultured bone by several different agents that alter Na transport, we proposed that hormonally stimulated bone resorption requires Na/Ca exchange. Calcemic hormones appear to interact primarily directly with the osteoblast, which then mediates the activation of osteoclast activity. In organ culture it is not possible to determine whether Na/Ca exchange is involved in this initiating step in the osteoblast or directly in osteoclast-mediated Ca release, and there have been no prior direct measurements of Na/Ca exchange in bone or bone cells. The purpose of this study was to demonstrate the presence of Na/Ca exchange transport in the osteoblast. Thus, we characterized Na-dependent Ca transport in osteoblast-like rat osteosarcoma cells (UMR-106) and primary bone cells isolated from neonatal mouse calvaria. Cells were loaded with the Ca-sensitive dye fura-2 in the presence of physiologic NaCl and the absence of Ca with or without 0.3 mM ouabain. Changes in free cytosolic Ca after the extracellular addition of 1.5 mM Ca were measured spectrofluorimetrically. An outward Na gradient was generated by decreasing extracellular Na while maintaining isotonicity. UMR-106 cells that were Na loaded by ouabain inhibition of Na,K-ATPase activity exhibited 30% greater Ca uptake than control cells. Similar results were obtained with primary bone cells. This uptake required extracellular Ca, was not inhibited by 200 microM verapamil, and was reversible upon reversal of the Na gradient. These data demonstrate the presence of a Na/Ca exchange transport system in osteoblasts. PMID- 1414502 TI - Restoring and maintaining bone in osteopenic female rat skeleton: I. Changes in bone mass and structure. AB - This experiment contains the crucial data for the lose, restore, and maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses anabolic agents to restore bone mass and architecture (+ phase) and then switches to an agent with the established ability to maintain bone mass, to keep the new bone (+/- phase). The purpose of this study was to learn whether switching to an agent known chiefly for its ability to maintain existing bone mass preserves new bone induced by PGE2 in osteopenic, estrogen-depleted rats. The current study had three phases, the bone loss (-), restore (+), and maintain (+/-) phases. We ovariectomized (OX) or sham ovariectomized (sham-OX) 5.5-month old female rats (- phase). The OX rats were treated 5 months postovariectomy with 1-6 mg PGE2 per kg/day for 75 days to restore lost cancellous bone mass (+ phase), and then PGE2 treatment was stopped and treatment began with 1 or 5 micrograms/kg of risedronate, a bisphosphonate, twice a week for 60 days (+/- phase). During the loss (-) phase, the cancellous bone volume of the proximal tibial metaphysis in the OX rat fell to 19% of initial and 30% of age-matched control levels. During the restore (+) phase, the cancellous bone volume in OX rats doubled. When PGE2 treatment was stopped, however, and no special maintenance efforts were made during the maintain (+/-) phase, the PGE2-induced cancellous bone disappeared. In contrast, the PGE2-induced cancellous bone persisted when the PGE2 treatment was followed by either a 1 or 5 micrograms treatment of risedronate per kg given twice a week for 60 days during the maintain (+/-) phase. The tibial shaft demonstrated very little cortical bone loss during the loss (-) phase in OX rats. The tibial shaft cortical bone fell some 8%. During the restore (+) phase, new cortical bone in OX rats increased by 22%. When PGE2 treatment was stopped and nothing was given during the maintain (+/-) phase, however, all but the PGE2-induced subperiosteal bone disappeared. In contrast, when PGE2 treatment was stopped and 1 micron risedronate per kg twice a week for 60 days was administered during the maintenance (+/-) phase, the PGE2 induced subperiosteal bone and some of the subendocortical bone and marrow trabeculae persisted.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1414504 TI - Hypocalcemic actions of amylin amide in humans. AB - Amylin (also known as islet amyloid polypeptide and diabetes-associated peptide) has recently been shown by us to have a potent hypocalcemic effect in rat and rabbit owing to inhibition of osteoclast-mediated bone resorption. The hypocalcemic potency of amylin was found to be second only to that of calcitonin (CT) and is 100-fold more potent than calcitonin gene-related peptide. Here we demonstrate that amylin has a hypocalcemic effect in patients with Paget's disease of bone. Both human CT (hCT) and amylin induced a maximum hypocalcemic effect 2 h following intravenous administration of the peptides (p less than 0.001). Although on a molar basis amylin is less potent than CT, it exhibits a significantly prolonged hypocalcemic effect compared to hCT. Here we demonstrate for the first time a profound hypocalcemic effect of amylin in the human, despite sharing only 15% amino acid sequence identity with hCT. PMID- 1414505 TI - Ultrastructure of the ventral lateral geniculate nucleus (LGNv) receiving tectal afferents in the cat. AB - The ultrastructure of the ventral lateral geniculate nucleus (LGNv) associated with the superior colliculus was investigated. In addition to normal synaptic morphology tectal input was examined following unilateral ablation of the superior colliculus at survival times of 2 to 12 days. Eight cats were used (six experimental, two control). Examination of the ventromedial LGNv revealed a prevalence of Flat-Symmetric (FS) synapses (58.2 +/- 1.9%), relative to the usually more abundant, Round-Asymmetric (RA) contacts (41.8 +/- 1.8%). The functional morphology of terminating tectal fibres (although infrequent) was suggestive of the FS type. Since FS connections usually serve an inhibitory purpose, it is suggested that the tectal LGNv connection has a negative modulation function in the fixation and tracking process. PMID- 1414506 TI - The method of surgical hippocampal lesions in dogs. PMID- 1414507 TI - Catecholamines and DOPAC in cortical and neostriatal regions during rats' learning of delayed alternation. AB - Dopamine, norepinephrine and DOPAC were measured in two cortical areas (the medial prefrontal and the posterolateral, Te2) and in the anterior and posterior neostriatum in rats which were exposed to three different experiences for three different lengths of time. One group learned delayed alternation and the two others served as controls. Throughout the training period all animals were housed in single cages. There was no significant effect of the kind of experience on any measure, but the length of exposure did affect some values: the amount of non precursor dopamine was decreased significantly in both neostriatal samples. A significant increase of dopamine turnover and amount of norepinephrine was found in the Te2 area and in the posterior neostriatal sample. The observed changes are attributed to isolation stress. We conclude that although, as it has been described earlier, dopamine transmission is necessary for mediation of behavioural functions of the prefrontal system, it does not change quantitatively in the system during specific activity. PMID- 1414508 TI - Chlorpromazine exerts stronger suppressive action on the instrumental responses motivated by social than by alimentary reward. AB - Experiments were performed on six dogs over-trained before treatment, in differentiation of two instrumental responses, i.e. reinforced either by food or by sensory-social reward (petting by the experimenter). Chlorpromazine was injected intramuscularly (1.5 mg/kg) in two separate series. In the first series the drug was given four times during two weeks (twice a week). In the second series, it was injected every day for four consecutive days. Chlorpromazine produced a decrease of performance and an increase of response latencies and errors but this effect was much more evident with social than with alimentary reward. The effect of the drug was similar in both variants of the experiment, although it was more pronounced in the second than in the first series. Food intake was not changed. The motor and autonomic disturbances produced by the drug were not correlated with the decrease in instrumental performance. It is suggested that chlorpromazine acts rather on motivational or rewarding processes than on hunger drive or instrumental performance as such. PMID- 1414509 TI - 5-HT1 receptors in the structures of visual pathway of normal and monocularly deprived kittens. AB - The density and pattern of distribution of 5-HT1 receptor sites was examined using quantitative in vitro autoradiography with [3H]5-HT as a ligand in the visual structures of 5 weeks old kittens. One group of animals had normal binocular vision, the other was monocularly deprived during the last three days of life. The density of 5-HT1 receptor sites and the pattern of their distribution in the visual structures showed distinct regional, areal and laminar differences. In the primary visual cortex (area 17) a high labelling density was found as compared with other cortical areas investigated. Three bands of high binding density were observed corresponding to cortical layers II-III, IV c and VI. This pattern distinguished area 17 from other cortical areas investigated. In subcortical visual structures very high labelling was present in the superficial visual layers of superior colliculus, but LGN showed rather weak labelling although the lamination of LGN was also seen in the pattern of distribution of 5 HT1 sites. Neither density nor pattern of 5-HT1 sites in the visual cortex and superior colliculus were affected by 3 days of monocular deprivation. High density of labelling and the distinct pattern of 5-HT1 receptor sites in the primary visual cortex suggest the important role of serotonergic transmission in the modulation of visual afferent input activity. PMID- 1414510 TI - Glycine enhances extracellular 45Ca2+ response to NMDA application investigated with microdialysis of rabbit hippocampus in vivo. AB - This study evaluates the role of glycine in in vivo modulation of the activity of excitatory amino acid receptors sensitive to N-methyl-D-aspartate (NMDA) in the rabbit hippocampus. Changes of extracellular calcium concentration were studied by the microdialysis technique combined with 45Ca-utilizing clearance method. The steady state level of amino acids in the dialysate was analyzed with HPLC. Pharmacologically active substances were applied directly to the hippocampus via the dialysis medium. Glycine concentration in the extracellular fluid of the hippocampus was in the range of 10(-5) M. Application of NMDA induced a drop of calcium concentration in the extracellular compartment of the hippocampus. This effect was inhibited by 7-Cl-kynurenic acid, an antagonist of glycine binding site on the NMDA receptors. Application of glycine and D-serine to the dialysis medium did not interfere with the basal level of extracellular calcium in the hippocampus, but resulted in an enhancement of the NMDA-induced decrease of calcium concentration. These results indicate that in the hippocampus the NMDA receptors are under constant positive modulation by endogenous glycine. Since glycine binding sites on the NMDA receptors are not saturated by an endogenous ligand, glycine may play a role in regulation of the NMDA receptor activity in the hippocampus in vivo. PMID- 1414512 TI - Motor units of medial gastrocnemius muscle in the rat during the fatigue test. II. Changes in the time course of sequential tetani of fatigue test. AB - Seventy motor units (MUs) of 3 types: fast fatigable (FF), fast resistant to fatigue (FR) and slow (S) were studied in medial gastrocnemius muscle of the rat. The fatigue test time course showed significant variability. It was found, that slow MUs, apart from greater resistance to fatigue, had less variable tetanic time course during the fatigue test than the fast MUs. The tetani of fast MUs were unfused with a marked sag. At the beginning of fatigue test the tension of fast motor units increased. The increase appeared to be greater and more rapidly developing in FF than in FR MUs. In the next part of fatigue test, when decrease in the tetanic tension was observed, the tetanic time course was changing in FF but not in FR MUs. During the first tetanus of fast MUs the sag exhibited a significant variability of its time course. In a proportion of fast MUs the sag appeared again when their tension was potentiated but in such a case it showed a different time course. The obtained results point to high degree of specialization of MUs in the studied muscle. PMID- 1414511 TI - Modulation of GABA transport in synaptosomes by histamine. AB - We have examined the effects of exogenous and intrasynaptosomal histamine on the GABA transport in rat brain synaptosomes. Exogenous histamine had no effect on GABA uptake, but inhibited veratridine-evoked GABA release. GABA uptake was susceptible to the modification of histamine synthesis in synaptosomes. The increase of synaptosomal histamine level by incubation under conditions favouring histamine synthesis from 2.6 to 5.2 pmole/mg protein, decreased the GABA uptake by about 75%. As demonstrated in experiments with an inhibitor of histidine decarboxylase--semicarbazide, this effect comprised 15% inhibition evoked by the histamine precursor--histidine, whereas the remaining 60% inhibition could be ascribed to the effect of newly synthesized histamine. PMID- 1414513 TI - Grading of supratentorial arteriovenous malformations on the basis of multivariate analysis of prognostic factors. AB - The case histories and angiograms of 93 consecutive patients who underwent surgery for arteriovenous malformations were analyzed retrospectively to find clinical and radiological prognostic factors influencing the outcome. A stepwise multiple regression was performed as follows. All radiological data such as size, location, and feeding and draining vessels as well as the clinical data such as age, sex, clinical grade on admission were introduced into the model and tested whether they contributed significantly to the prediction of the outcome which was the target variable. If so they were retained, otherwise eliminated. By this procedure the following features were identified as significant prognostic factors which adversely influence the outcome: poor clinical grade, feeding vessels from the A 1-segment and the anterior communicating artery, feeders from the M 1-segment, feeders from the Rolandic branches of the middle cerebral artery, a shunt through the anterior communicating artery. Neither the presence of a particular draining vein nor the type of the venous drainage when divided into superficial or deep had an influence on the outcome. Nor was the size of the lesion of significant importance. The bearing of these findings on the value of established grading systems is discussed and a new grading system is proposed. PMID- 1414514 TI - Are there typical localisations of lumbar disc herniations? A prospective study. AB - A prospective intra-operative analysis of the location of lumbar disc herniation was performed in 131 patients with verified 54% contained (incomplete) and 46% non-contained (complete) lumbar disc herniations. Bulging discs or protrusions are not included in this study. Complete disc herniations occurred more frequently in the upper lumbar spine. The localization of the lumbar disc herniations within its segment showed no correlation to the affected level. 64% of the disc herniations were located medio-laterally, 20% laterally, 12% within or lateral of the intervertebral compartment and 5% in the midline. Nearly one third of all herniations were found at the level of the disc space. Medio-lateral disc herniations were displaced more often in a caudal direction, lateral herniations were found displaced upwards and downwards with similar frequency while extraforminal herniations migrated significantly more often in a cranial direction. The pathomechanism and anatomical pathways of disc fragment migration are discussed on the basis of a new concept of the anterior extradural space. PMID- 1414515 TI - Postoperative spondylodiscitis: results of a prospective study about the aetiology of spondylodiscitis after operation for lumbar disc herniation. AB - In 412 patients undergoing surgery for herniated lumbar discs from September 1986 to September 1987 and from January 1988 to July 1989 a microbiological specimen was taken from the intervertebral disc space and from the cover of the operating microscope. Also the tips of the wound drains were examined microbiologically after removal. 17% of the patients had a positive bacteriological culture from their intervertebral disc space; 12% of the specimen from the operating microscope were positive. These results favour the hypothesis that intra operative contamination of the disc space, in contrast to haematogenous spread, causes spondylodiscitis. On the other hand we saw during this time course only one case of clinical spondylodiscitis, which implies a possible involvement of other predisposing factors such as pre- or perioperative infections or compromised patient immunologically. It is also possible, that the routine application of local antibiotic or antiseptic solutions into the disc space at the end of the operation could decontaminate the operative site and prevent clinical infection despite positive culture findings. PMID- 1414516 TI - Clinical outcome and cognitive impairment in patients with severe head injuries treated with barbiturate coma. AB - This study reports on clinical outcome in 38 patients with severe head injuries (posttraumatic coma for 6 hours or more) treated with barbiturate coma because of intracranial hypertension. Eighteen patients died, 4 patients remained in a severely disabled or a chronic vegetative state, and 16 patients reached the levels good recovery/moderate disability. Six of these patients returned to work or school full time, 4 for half time and 3 were in a rehabilitation program. Fourteen patients were subjected to a comprehensive neuropsychological assessment. All patients except one exhibited varying degrees of cognitive dysfunction and 6 patients had signs of personality change. The quality of life for the majority of surviving patients was relatively good but the positive effects of barbiturate coma therapy in the age groups over 40 years appeared to be limited. PMID- 1414517 TI - Results of continuous long-term intravenous application of octreotide via an implantable pump system in acromegaly resistant to operative and X-ray therapy. AB - Long term results after surgery for growth hormone (GH)-secreting adenomas indicate only a limited cure rate, particularly in patients with tumours invading the dural boundaries of the sella with suprasellar extension. Since octreotide had become a treatment option, it was used i.v. via an implantable pump system in five patients (age range 24-46 yr) showing symptoms of uncontrolled acromegaly, in spite of previous surgery and X-ray therapy. The octreotide doses used permanently for a cumulative treatment period of 8.8 yr ranged between 300 and 1000 micrograms/24 h. Serial evaluations of clinical findings, 24-h GH and insulin profiles, insulin growth factor-1 (IGF-1), oral glucose tolerance test and pituitary function revealed sustained GH suppression, without interim escape, below 2 ng/ml in two and below 5 ng/ml in three patients, IGF-1 decrease in all with normalization in two patients and no clinically relevant disturbances of carbohydrate tolerance or thyroid-stimulating hormone secretion. In one case of previous unresponsiveness to dopamine agonists i.v. octreotide application for 29 months facilitated later disease control by bromocriptine only. In two patients octreotide was terminated after 15 and 30 months of i.v. administration, respectively, because the effects of irradiation had occurred. For a subgroup of patients with resistant acromegaly continuous i.v. octreotide can be considered as a safe and effective alternative, which increases patients' independency from the inconvenience of daily repeated s.c. injections. PMID- 1414518 TI - Gangliosides in meningiomas: correlation of Glac2 to intermediary filament. AB - Human meninges and 29 meningiomas were analyzed as to their glycosphingolipid composition. In the neutral fraction GSL, a mostly even distribution of mono-, di , tri-and tetrahexoside was demonstrated. In the group of the gangliosides, Glac1 in one broad band in chromatograms occurred in almost all meningiomas; Glac2 was present in 84% of tumours. Members of the Gtn-family were only found in a small minority of tumours while various Gtet-gangliosides were detectable in nearly half of them. No constant pattern or patterns emerged and no correlation to either morphological subtype or malignancy grade could be established. Immunohistochemistry revealed focal presence of Glac2 in a pattern similar to that of vimentin expression. Semiquantitative evaluation showed good correlation between both parameters. PMID- 1414519 TI - Relationships between Ki-67 labelling index, amplification of the epidermal growth factor receptor gene, and prognosis in human glioblastomas. AB - The aim of this study was to determine possible relationships between Ki-67 labelling index (Ki-67 LI), amplification of the epidermal growth factor receptor (EGFR) gene, and prognosis in human glioblastomas. Ki-67 LI was determined on cryosections of biopsy specimens of 20 human glioblastomas with a mouse anti human Ki-67 monoclonal antibody. Amplification of the EGFR gene was determined by slot blot and Southern blot analyses of DNA extracted from the tumour biopsies. The Ki-67 LI was higher in the glioblastoma group with EGFR gene amplification (8 tumours, median value of Ki-67 LI 4.2, range 0.4-24.6) than in those without EGFR gene amplification (12 tumours, median value of Ki-67 LI 0.8, range 0.2-11.8) (0.05 p less than 0.1). The glioblastoma patients with Ki-67 LI greater than 1.5 (10 tumours) had a statistically significant shorter survival than those with Ki 67 LI less than 1.5 (10 tumours) (p less than 0.05). The glioblastoma patients with EGFR gene amplification lived shorter time than those without EGFR gene amplification (p greater than 0.05). PMID- 1414521 TI - Osseous metastases from a benign intraventricular meningioma. Case report. AB - The authors report a case of a 6 month-old male presenting with increasing head circumference and a large benign intraventricular meningioma which was grossly removed at the initial surgery. Twenty-four months later, the patient returned with subcutaneous and osseous metastatic lesions at the site of the previous craniotomy, revealing the same histology as the original tumour. The presentation, pathology and management of this unique case are discussed. PMID- 1414520 TI - Malignancy and viability of intraparenchymal brain tumours: correlation between Gd-DTPA contrast MR images and proliferative potentials. AB - The feasibility of diagnosing the malignancy and viability of intraparenchymal brain tumours using Gd-DTPA, enhanced and unenhanced T1-weighted MRIs was investigated. The relationship between the Gd-DTPA enhancement pattern, the growth fraction (GF) determined by using the anti-bromide-oxyuridine (BrdU) monoclonal antibody, the clinical condition, the proliferative potential and the change of Gd-DTPA enhancement over time was studied. Forty-five patients with intracranial tumours were studied with the static method of Gd-DTPA MRI. The enhanced effect in Gd-DTPA MRIs was dependent on tumour-cell density, vascularization, necrosis, and dilatation of vascular lumen. Tumour-cells were observed in eighty-seven of eighty-nine specimens taken from areas with Gd-DTPA enhanced MRIs. Seventy-four percent of these specimens (64 of 87) showed a malignancy of more than 5% growth fraction. On the other hand, tumour cells were observed in twenty-seven of fifty-six specimens taken from areas with Gd-DTPA unenhanced MRIs. Eighty-five percent of these specimens (23 of 27) showed a malignancy value of less than 5% GF. However, fifteen percent of these specimen showed values between 5 and 15% GF. In the kinetic study of Gd-MRIs five patients who were in a clinically stable condition and one patient who had radionecrosis showed a constant pattern of enhancement or slightly increased enhancement 30 min after injection compared to 4 min after injection. Therefore, GD-DTPA MRI can be used effectively in the diagnosis of tumour viability and malignancy after treatment. PMID- 1414523 TI - Changes in mechanical responsiveness of the rat aorta after cervical spinal cord stimulation. AB - The effect of cervical spinal cord stimulation on the mechanical vascular responsiveness of rat aortic artery rings was studied "in vitro". Arteries with and without endothelium from sham and stimulated male Wistar rats were placed in an organ bath studying the contractile response induced by noradrenaline, prostaglandin F2 alpha and serotonin. For spinal cord stimulation two electrodes were placed in the cervical epidural space using microsurgical technique. The parameters of stimulation were: monophasic waveform current, pulse width of 0.1 ms, frequency of 120 cps, and intensity one third of the threshold which produced motor responses (between 0.3 and 0.5 v). The total period of stimulation was 120 minutes. The potency of each vaso-active agent was calculated in the organ bath for each experimental group. There were differences only when arteries with endothelium from sham (7.2587 +/- 0.2308) and stimulated (8.0720 +/- 0.3723) rats were tested with noradrenaline (p less than 0.01). Our results suggest that cervical spinal cord stimulation induces changes in the vascular wall that might explain the effects of spinal cord stimulation on vasomotor control. PMID- 1414522 TI - Experimental study on the indications for barbiturate therapy. Change in haemodynamics and the influence of dopamine. AB - The effect of barbiturates on the cerebral haemodynamics and the influence of dopamine on barbiturates were investigated using 20 cats, and clinical indication of barbiturate therapy is discussed. Cerebral blood flow, oxygen extraction fraction, and cerebro-vascular resistance as well as physiological variables were evaluated at various concentrations of barbiturates in the blood. Thiamylal caused simultaneous reduction of mean arterial blood pressure and cerebral blood flow. As the disruption of autoregulation proceeded, cerebro-vascular resistance and oxygen extraction fraction increased till the barbiturate-induced coma stage. Furthermore, cerebro-vascular resistance increased much more markedly by the combined use of dopamine. Clinically, our results indicate barbiturates would increase cerebral circulatory disturbances caused by vasospasm following subarachnoid haemorrhage because barbiturates further increase cerebro-vascular resistance. Then again, the combined use of dopamine is not preferable because of deterioration in vasospasm. PMID- 1414524 TI - The use of coaxially aligned freeze-thawed skeletal muscle autografts in the repair of the cauda equina--in the sheep. AB - The aim was to develop a model for study of nerve regeneration in nerve roots above the level of the dorsal root ganglion and to investigate the use of freeze thawed muscle autografts for repair of nerve roots at this level. Four adult sheep were used for the experiment. A laminectomy was performed at the lumbosacral junction and the S2 root identified. Both the dorsal and ventral S2 roots were divided unilaterally within the dura and a freeze-thawed muscle graft was inserted into the nerve gap. When assessed at 6 months an action potential was recordable from the ventral root in one sheep. Histological examination of the nerve roots showed evidence of regeneration across the graft in the ventral roots of all the sheep and the dorsal roots of some. This preliminary work indicates a capacity for regeneration of the cauda equina and that freeze-thawed muscle can support this. It provides a useful model for further study of nerve root repair. PMID- 1414525 TI - Ethico--legal aspects of high risk neurosurgery. PMID- 1414526 TI - Jugulare foramen paragangliomas. AB - A survey is given of the clinical picture, diagnosis and management of foramen jugulare paragangliomas (JFP), based on reports of 175 cases from the literature and personal experience of 26 cases. Special emphasis is given to the operative techniques. Improvements of diagnostic possibilities as well as operative techniques, including the pre-operative occlusion of tumour-feeding arteries by endovascular methods have markedly reduced the operative mortality to a rate between 0 and 5 percent. The rate of incomplete removal of C and D tumours dropped to about 15%. But very large and extensive tumours remain a real challenge. Teamwork between neuroradiologists, ENT-surgeons and neurosurgeons is mandatory. PMID- 1414527 TI - Experience with 36 surgical cases of petroclival meningiomas. AB - Thirty-six patients with petroclival meningiomas underwent surgery between 1978 and 1990. The tumours accounted for 13% of a total of 284 skull base meningiomas operated upon during the same time period. The most frequent neurological signs related to cranial nerve deficits, mainly of the 8th, 5th, and 7th nerves respectively. The approaches to the petroclival region were: retromastoid, pterional, subtemporal, and combined retromastoid-subtemporal. In 12 patients we used a modification of the retromastoid-subtemporal approach with preservation of the sigmoid and transverse sinus (presigmoid approach). "Total" tumour removal was achieved in 27 cases (75%). There was no postoperative death, and in 83% of cases no severe morbidity. With careful pre-operative evaluation, improved operative approaches and microsurgical techniques the treatment of petroclival meningiomas has been considerably improved. PMID- 1414528 TI - Surgical treatment of anterior third ventricle tumours. AB - A review is given on the operative management of anterior third ventricle tumours, with special emphasis on the selection of the approach, the postoperative results and complications. The review is based on our own experiences with 337 cases and 340 operations, among them 198 craniopharyngiomas, 80 gliomas, 23 colloid cysts, 11 ependymomas, and 25 others. The tumours can be approached through the lamina terminals or transcallosally or using a combination of both of these approaches. The approach through the lamina terminalis is useful only in rather small tumours, because it does not allow a sufficient revision of the upper and posterior third ventricle compartments. For larger tumours the transcallosal approach is preferable. We have abandoned the approach through the anterior horn of the lateral ventricle, because it does not allow an equally good vision of both sides of the third ventricle. In some of the craniopharyngioma cases it was necessary to combine the transcallosal and subfrontal approaches in order to achieve total or subtotal tumour resection. In craniopharyngiomas total or subtotal tumour removal was possible in 66% of the children and 59% of the adult patients, with a mortality higher in adults (30%) than in children (18.5%). The main causes of complications in craniopharyngiomas were acute disturbances of hypothalamic circulation and function, with water-electrolyte imbalance and other signs of diencephalic insufficiency. In glioma cases an additional important cause of complications has been haemorrhage into the remaining tumour parts. Colloid cysts could be exstirpated without mortality, using the transcallosal approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414529 TI - Tumours of the limbic and paralimbic systems. AB - Clinical manifestations, findings, management and outcome of a series of 177 cases with tumours of the limbic and paralimbic systems are presented. There was no operative mortality. Postoperatively 95% of them had no or only minor neurological deficits. Most of them were able to resume work. Pre-operatively 77% of the patients had epilepsy, but 84% became seizure-free after tumour removal. All 77 cases with malignant tumours died within 1-5 years. In the past many neurosurgeons were reluctant to attempt complete tumour removal in these areas. This series demonstrates the efficacy of highly skilled microneurosurgery. PMID- 1414530 TI - Surgical experiences with giant intracranial aneurysms. AB - The common method of presentation of intracranial aneurysms is at the time of their rupture (with subarachnoid haemorrhage) or on the occasion of their compression of neighbouring structures. While giant aneurysms may occasionally present with subarachnoid haemorrhage, their more common methods of presentation are due to their space occupying and neighbourhood effects. Giant aneurysms are commonly defined as those with a diameter larger than 2.5 cm. Previously this diameter was assessed either by arteriography, so that size meant internal diameter, or by the displacement of surrounding structures, as for example, small perforating vessels, which could be attributed positively to the presence of a larger mass. Before CT scanning however, the factor of a very considerable larger aneurysm, partly occluded by clot could occasionally cause unexpected operative difficulty. The advent of CT scan and now especially MR imaging has made the prediction of the size of the aneurysm much easier and the extent of the intra aneurysmal clot also clearly definable. This paper describes one surgeon's experience with 64 giant cerebral aneurysms operated on in the last 10 years (Table 1). It has emerged from this experience that the most satisfactory method of handling the lesion is to remove the intra-aneurysmal clot and clip the neck of the aneurysm, and the steps necessary to secure this laudable design from the burden of the paper. PMID- 1414531 TI - Multiple intracranial aneurysms: a high risk condition. AB - There is still a relative silence in the literature on what policy should be followed in treating multiple aneurysms. The main risks are: bleeding of a formerly asymptomatic aneurysm during the haemodynamic tides of the peri operative period; aneurysm(s) can be hidden on angiograms and tend to be overlooked easier in case of an already revealed aneurysm; misjudgement of the ruptured one as a silent additional aneurysm, therefore left for second stage surgery. This paper, based on a material of 330 operations for multiple aneurysms, focuses on these problems. It advocates the one stage complete repair of all lesions using both options of bilateral pterional craniotomies or the contralateral approach. But it also describes those silent aneurysms which safely could be clipped later. Hazards and disadvantages concerning the more aggressive surgery proved to be less significant than the natural history of multiple aneurysms represents. PMID- 1414533 TI - Interventional neuroradiology for the treatment of inaccessible arterio-venous malformations. AB - Embolization of cerebral arterio-venous malformations (AVM) has been performed at the Department of Neuroradiology of Verona in 136 patients with a total of 310 procedures. The complication rate was 16%. In most of the cases embolization was followed by either operative removal of the AVM or by radiosurgery. In a group of 38 embolized patients, who refused operation or radiosurgery, rebleeding occurred 7 times (18%), but only in patients who already had bleedings before embolization. Indications and techniques of embolization are described and discussed. PMID- 1414532 TI - Transoral approach to anterior brain stem compression. PMID- 1414534 TI - Evaluation of intracranial pressure gradients by means of transcranial Doppler sonography. AB - The authors investigated the effects of intracranial pressure gradients generated by a unilateral intracranial mass on transcranial Doppler (TCD) readings. Eleven patients harbouring a symptomatic chronic or subacute subdural haematoma underwent pre- and post-operative TCD examinations of the intracranial internal carotid and middle cerebral arteries. Mean values of velocity and pulsatility index (PI) were compared to the contra-lateral counterpart. The haematomas were evacuated by means of burr hole drainage under local anaesthesia. Symptomatic subdural haematomas lowered the ipsilateral blood velocity in the internal carotid and middle cerebral arteries by a mean side-to-side difference of 15.64 +/- 3.01 m.sec-1. The ipsilateral PI was higher than the contralateral values by an average of 0.23 +/- 0.04. Low mean velocity and high PI values were associated with high subdural pressure. Abnormal pre-operative ipsilateral TCD readings returned to normal following haematoma drainage. We postulate that intracranial pressure gradients generated by the subdural mass lesion are responsible for the asymmetry of TCD readings. These differences should be considered in the interpretation of post-subarachnoid haemorrhage vasospasm, as it is frequently associated with lateral clots. Our findings also provide a useful method for non invasive monitoring of intracranial pressure gradients. PMID- 1414535 TI - HM-PAO spect in head trauma. AB - Single Photon Emission Computed Tomography (SPECT) after intravenous administration of Technetium-99m hexamethylpropylene-amine oxime (Tc-99m HM-PAO) makes possible the evaluation of cerebral perfusion. We have been assessing the diagnostic accuracy of SPECT in some groups of head trauma patients: the preliminary results of this study are presented. Fourteen patients have been selected, all of them showing some kind of focal neurological deficit; the Computed Tomography (CT) and Nuclear Magnetic Resonance (NMR) were normal, or showed lesions that could not be responsible for the neurological deficits. In all of the patients Tc-99m HM-PAO SPECT has been performed, showing changes in cerebral perfusion in areas correlated with the abnormalities elicited on clinical examination. These results show that Tc-99m HM-PAO SPECT is a better technique than CT or NMR in demonstrating the organic basis of some neurological deficits observed after head trauma. PMID- 1414536 TI - Early post-traumatic cerebral blood flow mapping: correlation with structural damage after focal injury. AB - Focal post traumatic mass lesions such as contusions and intracerebral haematomas are common, and often difficult for neurosurgeons to manage, because little is known of their pathophysiology. We have mapped cerebral blood flow, and studied small vessel ultrastructure at different time points within the first three weeks of head injury, in patients with these lesions. A zone of ischaemic brain is always present around these lesions, and persists for weeks or months. This accords with astrocyte swelling and microvascular compression seen on electron microscopy. Focal zones of hyperaemia were also present in 42% of patients, within the first two weeks of injury, and this appeared only within apparently normal tissue as judged by late MRI or CT. PMID- 1414537 TI - The role of computer based techniques in patient monitoring: technical note. AB - In this paper the requirements of Neurophysiology and Neurotraumatology monitoring are analyzed. As a result a set of designated systems were developed by the authors a short description of which is given in the paper. Finally the future perspectives and problems to be faced are briefly described. PMID- 1414539 TI - Blunt basal head trauma: aspects of unconsciousness. AB - Two cases of street violence directed to the skull base level and transverse to the cervical axis are described. No skeletal damage. The violence resulted in the so-called "traumatic subarachnoid haemorrhage", an often used, unspecified forensic "diagnosis"; it was here revealed to be due to rupture of the wall of the posterior inferior cerebellar artery (p.i.c.a). However, this was only one of the possible explanations for the acute symptoms of unconsciousness (concussion) and almost immediate death. The careful examination of these two cases and of a series of control cases revealed that at the trauma, stress and strain may have occurred to arterial branches serving as feeding perforant vessels to the medulla oblongata; in these cases they were coursing directly from the p.i.c.a. region.- The type of direct impact has often been regarded as mild! However, its location suboccipitally as in these cases can become dangerous. The resulting direct or indirect deficit of brain stem functions are discussed in these cases as well as "concussion-related symptoms" resulting after other types of head and neck injury. PMID- 1414538 TI - Significance of endocrine studies in the general assessment and prediction of fatal outcome in head injury. AB - Serial basal blood glucose, serum insulin, cortisol, growth hormone, glucagon and catecholamine examinations were performed in 81 brain-injured patients. 32 patients with severe injuries of other parts of the body (chest, abdomen, limbs or polytrauma), and 17 patients with non-traumatic acute brain lesions served as double control. In the brain-injured patients there is a close relation between changes of the state of consciousness and those of basal blood glucose levels: the deeper coma the higher and wider is the pathological glucose-level range. Four types of blood-glucose changes could be identified in the background of which different alterations of each hormone level were observed. Fatal outcome could be predicted in a non-diabetic patient in the first days when seeing: 1) Fasting hyperglycaemia above 14 mmol/l; 2) Fluctuating basal blood glucose levels between 5 and 22 mmol/l; 3) Deeply depressed and unchanged basal insulin level; 4) Extremely high cortisol level; 5) Decreased plasma epinephrine level. These changes in the carbohydrate metabolism seen after acute brain lesions are not identical to diabetes mellitus. PMID- 1414540 TI - Primary traumatic benign midbrain haematoma in hyperextension injuries of the head. AB - Primary traumatic brain stem injury occurring in isolation is not universally recognized as a distinct pathological entity which may follow a head injury. We describe two patients with clinical and radiological evidence of primary posttraumatic midbrain haemorrhage occurring in isolation associated with good recoveries. It is suggested that paramedian midbrain syndromes associated with midbrain haemorrhages should be recognized as a distinct, although unusual, complication of hyperextension injury to the head which may have a benign course. PMID- 1414541 TI - The prognostic value of some clinical and diagnostic factors in traumatic intracranial haematoma. AB - In order to carry out the analysis of predictive values of some clinical and diagnostic features, 146 patients of the Neurosurgical Clinic of the Silesian School of Medicine, were examined in 1980-1986. All the patients were in coma when admitted while CT findings showed traumatic intracranial haematomas. The examination included neurological diagnosis and CT examination. The analysis of statistical discrimination let us specify the probability of predicting death or survival of every patient. On the basis of 10 prognostic factors applied, the compatibility of prognosis and the real outcome for patients who survived was 78.2% and for those who died 91.2%. PMID- 1414542 TI - Coexisting diffuse axonal injury (DAI) and outcome of severe head injury. AB - The importance of coexisting diffuse axonal injury (DAI) and outcome were studied in 107 patients with diffuse and focal brain injury. Comprehensive neuropathological study was undertaken in 26 fatal patients. There was a clear rank order of the mortality rate in the lesion type. The rank order of good recovery and moderate disability was also similar to the inverse of the mortality ranking. The pathological "marker" of DAI, macroscopic lesions in the corpus callosum and dorsolateral quadrant of the upper brainstem and histological evidence of axonal retraction balls, were commonly found not only in patients with diffuse brain injury but also in focal brain injury. The type of intracranial lesion in severe head injury is thus an important factor in determining outcomes and DAI of varying severity is the common subjacent lesion in the fatal patients. PMID- 1414543 TI - Brain oedema and intracranial hypertension treatment by GLIAS. AB - The authors present their results regarding the use of a buffered solution of glycerol 30%-sodium ascorbate 20% (GLIAS) for the treatment of brain oedema and intracranial hypertension. GLIAS was perfused intravenously in 80 patients with several types of brain oedema. In every patients serum and urinary osmolarity, diuresis, main blood and urine parameters, and ICP were monitored. Following GLIAS infusion an increase in plasma osmolarity was observed, changing the average basal value plus 13.4% after 15 min., 10.5% after 30'. At the same time there was a reduction of ICP and improvement in cerebral compliance. In each case there was a decrease in intracranial hypertension and brain oedema without significant collateral effects. PMID- 1414544 TI - Sedatives and antagonists in the management of severely head-injured patients. AB - Continuous intravenous sedation is often prescribed during the intensive treatment of severe head injury. It is known that intravenous hypnotics may prevent or treat the brief intracranial hypertension episodes associated with nociceptive stimuli, like tracheal intubation. However there is yet no clear evidence in the literature showing beneficial effects of sedation in severely head-injured patients on intracranial pressure control or outcome. Sedation should be primarily administered in neurotraumatology to allow good conditions for intensive treatment, while avoiding any depressive cardiovascular action. The abrupt reversal of sedation by means of specific antagonists may induce significant elevation of both cerebral blood flow and intracranial pressure and should be avoided. PMID- 1414545 TI - Indomethacin (Confortid) in severe head injury and elevated intracranial pressure (ICP). AB - In five head-injured patients with cerebral contusion and oedema in whom it was not possible to control ICP by hyperventilation and barbiturate sedation, indomethacin (Confortid) was used as a cerebral vasoconstrictor drug. In all patients indomethacin reduced ICP to below 20 mmHg for several hours. Studies of cerebral circulation and metabolism during indomethacin treatment showed a decrease in cerebral blood flow (CBF) at 2 hours. After 7 hours, ICP remained below 20 mmHg in three patients, and these still had reduced CBF. In two patients a return of ICP and CBF to pretreatment levels was observed. In all patients indomethacin treatment was followed by a fall in rectal temperature. Outcome scaling has not yet been performed, but all patients left hospital without neurological deficits. The results suggest, that indomethacin is an alternative in the treatment of ICP-hypertension in head-injured patients. PMID- 1414546 TI - Posttraumatic epilepsy in civilians: clinical and electroencephalographic studies. AB - Posttraumatic epilepsy (PTE) is a known consequence of head trauma. The factors involved in posttraumatic seizures generation and the relationship between acute seizures and posttraumatic epilepsy are not without controversy. This also applies to the evolution of the electroencephalographic characteristics. The study here reported was performed analysing data from patients with posttraumatic epilepsy (N = 205) and data from patients followed-up since trauma and considered as a high risk population for the development of PTE (patients with acute seizures and/or patients with focal lesions--contusion, haematomas or penetrating head injury) (N = 152). Seizure type was associated with age and trauma severity (children, elderly and worst trauma cases present with a higher proportion of partial seizures). Neurological deficit and lesion location were associated with the seizure occurrence. The increased incidence of seizures was found when the most diffused brain dysfunction was combined with neurological deficits. The analysis of sequential EEGs performed at first, at 6th and 12 months post trauma revealed a non-stationary pattern throughout these time periods with EEG focal abnormalities remaining frequent for more than two years after the trauma. Children and old people have a higher proportion of EEG abnormalities with more frequent abnormal generalized activity in children and more frequent abnormal focal EEG activity in the elderly. PMID- 1414547 TI - Monitoring of severe head-injured patients with transcranial Doppler (TCD) ultrasonography. AB - Intracranial haemodynamics were studied in 36 patients with severe head injury and experimental animals with acute intracranial hypertension by the use of TCD ultrasound. The mean flow velocity (FV) in the basal cerebral arteries commonly decreased on the side of the haematoma depending on intracranial pressure (ICP) elevation and cerebral perfusion pressure (CPP) reduction in focal brain injury. The FV decreased bilaterally and there was no difference between the right and left sides in diffuse brain injury without a clear relationship between the FV and CPP. The FV of the middle cerebral artery and blood flow in the internal carotid artery exhibited flow patterns which changed correlatively depending on CPP reduction in experimental animals. Monitoring with TCD ultrasound is valuable in evaluating compression ischaemia in focal brain injury. But many complicated factors are considerable in diffuse brain injury. PMID- 1414548 TI - Risk factors for late posttraumatic epilepsy. AB - The usually accepted risk factors for late post-traumatic seizures (LPTS) are those identified years ago by Jennet: early post-traumatic seizure (EPTS), depressed fracture, intracranial haematoma. Prolonged unconsciousness (PTA greater than 24 hrs) is another factor usually added. More recently, personal experience of the Authors and the data of the literature, compel us to question the validity of known risk factors based on clinical data. Authors believe that the identification of patients at risk for LPTS depends mainly on the precise definition of trauma severity and on CT or surgically documented lesions of brain substance. Three groups of patients, characterized by the presence of one or more of the accepted risk factors of LPTS, have been studied. In our experience, while in adults the presence of documented cortico-subcortical lesions represents the main risk factor of LPTS, in children the appearance of EPTS per se increases the risk of LPTS, irrespective of the presence of documented brain lesions. Alteration of consciousness without a focal lesion, even if prolonged and severe, is not a risk factor for LPTS. PMID- 1414549 TI - Mental deterioration at epilepsy onset: a hypothesis. AB - In this study, we hypothesized a type of mental deterioration in epilepsy, characterized as a discontinued, cascading process, i.e. a sudden mental decline in a limited time interval, immediately after the onset of the seizures. The posttraumatic epilepsy model (PTE) may appear to be exceptionally useful in avoiding one of the major methodological obstacles for testing this hypothesis, i.e. the unavailability of test results obtained with the same battery of tests prior to and directly after the onset of the seizures. We propose a multicentre study in which a large group of patients are assessed, after recovering from the direct aftermath of head injury, but before the onset of PTE. This baseline provides an opportunity for longitudinal follow-up. Full recovery from head injury before the onset of PTE is to be expected in the mild and moderate groups of closed head injury patients. In this category, approximately 2000 head injured patients have to be assessed to obtain a reasonable group of approximately 100 200 PTE patients. This group will be followed during the critical period of 2-3 years after the onset of epilepsy. PMID- 1414550 TI - Rehabilitation after severe head injury. AB - 123 survivors of severely head injured patients presenting with coma grade III show a decreasing mean duration of coma with increasing age. The numbers and frequency of good recovery decrease, whereas poor recovery increases with age. Increase of the duration of coma grade III produces an increase of the mean latency and time of recovery and of the frequency of poor recovery, regardless of the age of the patients. Increasing age does not increase the mean latency and time of recovery systematically. The important conclusion of this analysis is, that the clinical feature of coma grade III, corresponding to GCS score of 4 and RLS of 6 and 7, indicates a different kind of brain damage at various age groups. It represents a lesser degree of brain damage for younger patients under 20, than for those over 20. In our opinion our observations do not demonstrate a better capacity of recovery of the young patients: but the young patients show a more severe clinical picture than the older patients do, if only the clinical syndrome of coma grade III with extensor rigidity, is considered as a yardstick for comparison. PMID- 1414552 TI - Comparative study of magnetic resonance and CT scan imaging in cases of severe head injury. AB - The distribution, frequency, and appearance of head injuries were evaluated with MRI and CT in a prospective study of 155 patients with acute (n = 124) and chronic (n = 31) head injuries. MRI was significantly more sensitive than CT in the detection of intraaxial injury at any stage. In severe cases, central structure lesions were detected in approximately 80% of patients. Severity on admission was compatible with MR findings. However it was difficult to decide on neurobehavioural prognosis from initial MRI findings only. PMID- 1414553 TI - Oculo-dento-digital syndrome (Gorlin's syndrome): clinical and genetical report of a new family. AB - Here we report a family in which the Gorlin's syndrome or oculo-dento-digital dysplasia is transmitted with autosomal dominant inheritance of variant expressivity. Three cases, extensively studied, show also slight oligophrenia, symptom rarely described in this syndrome. PMID- 1414551 TI - Social-economic impact of head injury. AB - The socio-economic costs of traffic road accidents were analysed data epidemiological studies and compared with reported data. The costs are calculated as a function of accident type and vehicle involved, severity of head trauma, patients individual characteristics, type of care--intensive and emergency services, other hospital bed costs, including recovering and rehabilitation such as in-and out-patient services. Finally the costs of repairing materials (cars, walls, roads, etc.) are also estimated. The author concludes that the medical doctor must take part in compiling the statistics so as to be able to discuss the economics of injury and the social priorities. PMID- 1414554 TI - Hemianopic ataxic hemiparesis. A case report. AB - Ataxic hemiparesis and homonimous hemianopia developed in a hypertensive 60-year old woman. Magnetic resonance imaging detected multiple lesions in the territory of distribution of the posterior cerebral artery and in the inferior region of the left cerebellar hemisphere. At computed tomography only a right hypodense area involving the posterior right thalamus, the postero-medial region of the temporal lobe and the occipital lobe was evident. PMID- 1414555 TI - Effectiveness of oxiracetam therapy in the treatment of cognitive deficiencies secondary to primary degenerative dementia. AB - The effectiveness of oxiracetam (1600 mg/day) vs placebo was assessed in a group of 96 out-patients suffering from cognitive disorders secondary to primary degenerative dementia. The study, performed in double-blind, lasted 26 weeks and is expected to be continued in open conditions until a whole year of treatment is completed. The assessment of the results obtained at 6 months was carried out following both the methodology based on neuropsychological tests and scales, and the study of the simple reaction time by any of a computerised portable tachystoscope. The patients treated with oxiracetam showed a statistically significant improvement of cognitive function and simple reaction time. No significant variations in the scores of the tests used were observed in the placebo group. The patients themselves appeared in favour of oxiracetam. The drug tolerability proved to be very good for the whole duration of the treatment. The authors believe that oxiracetam favourably acts on the symptoms of senile cerebral deterioration and can improve the capability of information processing, as suggested by the better performances obtained at the reaction time tests. PMID- 1414556 TI - Acute encephalopathy following lumbar myelography with iohexol. AB - We report an unusual case of an acute encephalopathy following injection of iohexol for myelographic study, which was reversible after a treatment with water restriction and glucocorticoids. The pathophysiologic mechanism appears to be related with hyponatremia. We conclude that drinking of large amounts of fluids must be not recommendable in order to avoid the developing of encephalopathy. PMID- 1414558 TI - Sneddon's syndrome, anticardiolipin antibodies and anticardiolipin cofactor. A case report. AB - Sneddon's syndrome is a rare entity characterized by idiopathic livedo reticularis and cerebrovascular lesions. A case of a young woman with livedo reticularis and progressive cerebral arteriopathy is described. Abnormalities of sexual and gonadotropic hormones were present. Anticardiolipin and anticardiolipin-cofactor complex antibodies were not found. PMID- 1414557 TI - Metoclopramide-induced parkinsonism and depression. AB - A 46-year-old female patient with metoclopramide-induced parkinsonism and depression was reported in view of the rarity of the concurrent development of these side effects. A risk of metoclopramide administration is suggested. PMID- 1414559 TI - Correlation between the growth hormone and degenerative pathology. PMID- 1414561 TI - Isolated amnesia following a bilateral paramedian thalamic infarct. Possible etiologic role of a whiplash injury. AB - A previously healthy 45 years old carpenter suffered a whiplash injury in a road accident on July, 18th, 1990. He continued to work in spite of occipital headache, episodic sweatening and slight hypersomnia. On August, 8th, 1990 while parking his car into the deck of a ferry-boat he was found slightly confuse and markedly amnestic. A post-traumatic subdural haematoma was suspected. As a CT scan of the brain was normal, a toxic encephalopathy or an hysterical amnesia were proposed. However, a MRI performed on August, 22th, 1990, apart from a small infarct in the white matter of the left occipital lobe, showed two small bilateral paramedian thalamic infarcts. The last lesions usually follow a thrombotic or embolic occlusion of the "basilar communicating artery" (BCA) belonging to the vertebro-basilar system. The possible etiologic relationship between this syndrome and the previous whiplash injury has been considered. Six months later, while a control MRI showed a reduction of the brain lesions, a neuropsychological examination revealed a slight improvement of memory dysfunction evident also at a distance of further 6 months. This case is interesting because it tests the high sensitivity of MRI in amnestic syndromes and because of the possible role of a whiplash injury in the etiology of BPTI. PMID- 1414560 TI - Neurological damage mediated by cytokines. AB - Our results suggest that CKs, in particular Interleukin-1 and Tumor Necrosis Factor (TNF)-alpha, are involved in the pathogenesis of some neurological disorders and HIV infection. Infact, we observed an exaggerated spontaneous release of TNF-alpha in patients with migraine without aura. Furthermore, in a broad spectrum of patients with HIV-infection we have also found increased amounts of serum TNF-alfa and IL-1. Interestingly, a strict correlation between plasma lipopolysaccharide (LPS) and IL-1 or TNF-alpha levels seems to exist in both group of patients, thus indicating that LPS could account for the production of CKs in the course of the above diseases. PMID- 1414562 TI - Verbalized anger and accusatory "you" messages as cues for anger and antagonism among adolescents. AB - This study investigated the impact of communications of negative feelings between adolescents in close relationships. High school boys and girls were asked to imagine discussing a relationship problem with a personally close partner and to rate likely reactions to four kinds of statements: assertively expressed distress, assertively expressed anger, aggressively expressed distress, and aggressively expressed anger. Accusatory "you" statements were rated as more aversive and evoked stronger antagonistic response inclinations than assertive "I" statements. Statements depicting anger were rated as more aversive and evoked stronger antagonistic response inclinations than statements depicting distress. Results were similar for boys and girls. Implications of the findings and directions for further research are discussed. PMID- 1414563 TI - The effects of a psychoeducational program on adolescents' activity involvement, self-esteem, and locus of control. AB - Adolescents' participation in extracurricular activities is related to a number of variables, such as higher grade point average, increased self-esteem, and lower absenteeism. This research, part of a larger longitudinal study, was designed to determine whether a short, psychoeducational intervention, the personal empowerment program, would affect adolescents' level of involvement in activities, their self-esteem, or their locus of control. Fifty-two ninth-grade students who were average participators were randomly selected and assigned to either the empowerment program or control group. Students were surveyed six months after the program. Analyses of covariance using pretest scores as the covariates indicated that students who participated in the program maintained their level of activity involvement during the transition to high school, a time when participation generally decreases. The program did not produce significant changes in self-esteem or locus of control. Implications for future research are discussed. PMID- 1414564 TI - Reliability and validity of the Korean Youth Depression Adjective Check List (Y DACL). AB - To develop a Korean version of the Youth Depression Adjective Check List (Y DACL), bilingual Koreans achieved consensus in their translation of the 22 adjectives. Four hundred and seventeen male and 412 female adolescents from 8th through 12th grade of four Korean public schools (mean age ranged from 13.4 to 17.3) completed the state form of the Y-DACL, the Beck Depression Inventory (BDI), and the Self-rating Depression Scale (SDS). Internal consistency was high (alpha = .87), split-half reliability was moderately high (.72), and test-retest reliability was low (.26) as expected. Estimates of concurrent validity indicated a moderate level of correlation between the Y-DACL and the BDI and SDS. The findings suggest that the Korean Y-DACL is suitable for use in research. PMID- 1414565 TI - Evaluating the efficacy of short-term counseling on adolescents in a school setting. AB - This study evaluated the efficacy of short-term school-based counseling with forty-two high school adolescents (twenty-seven males, fifteen females) by measuring pre- and posttest scores on a self-report, self-esteem measure. While there was a significant decline in self-esteem ratings after counseling in the areas of social acceptance, job competence, and close friendship, counseled students showed a significant improvement in the consistency between their adequacy ratings and their judgments about what competencies they valued. Specific gender differences emerged, as females appeared to have benefited more from the counseling experience than did males. PMID- 1414566 TI - The use of the MMPI special scales in the assessment of delinquent personality. AB - The MMPI was administered to 401 adjudicated male juvenile offenders, ages 13 to 17, who had been referred to a juvenile court mental health unit for recommendations in court disposition. Mean T scores generated by 86 MMPI clinical and supplementary scales were tabulated and analyzed as to their relationships with completed court offense histories. Twenty-eight of these scales that best described and discriminated between high and low levels of recidivism, crime severity, assault, and property offenses were identified, profiled, and discussed. Data were analyzed by a suggested T-score cutoff of 1.5 standard deviations, univariate, and multivariate (discriminant) analysis. Scales that best discriminated between high and low levels of recidivism and property offenses were Pd (Psychopathic Deviance), Ma1 (Amorality), Pd2 (Authority Problems), Re (Social Responsibility), and MAC (MacAndrew Alcoholism). Low scores on Re (Social Responsibility), Es (Ego Strength), Cn (Control), and St (Social Status) best discriminated between high and low levels of crime severity. High and low levels of assault were best differentiated by Ma3 (Imperturbability), Scale 5 (Masculinity-Femininity), and Pa2 (Poignancy). Although the linear combination of Scales F, 4, 8, and 9 has some utility in the areas of recidivism and property offenses, its discriminative ability is extremely poor for levels of assault and crime severity. PMID- 1414567 TI - A comparison of the perceptions of the mother-daughter relationship of black pregnant and nonpregnant teenagers. AB - This study examined the relationship between mothers and their teenage daughters in order to determine if there was a significant difference in perceived relationships between pregnant and nonpregnant mother-daughter dyads in a predominantly black sample. Results indicated that the nonpregnant daughters and their mothers felt significantly more intimacy toward each other than did the pregnant daughters and their mothers. However, correlations of the mother and daughter scores revealed that the intimacy scores of the mothers of the pregnant daughters were positively correlated with their daughters' attachment scores, suggesting that the mothers and their pregnant daughters were more in agreement regarding their relationship than were the nonpregnant mother-daughter pairs. PMID- 1414568 TI - The association between teacher attitudes, behavioral intentions, and smoking and the prevalence of smoking among seventh-grade students. AB - Seventh-grade students and teachers from twenty-three middle and junior high schools were surveyed to determine the association between teacher attitudes, behavioral intentions, and smoking behavior and the prevalence of student smoking. Teacher attitudes toward smoking policies were found to be strongly related to the current smoking behavior of the teacher but not consistently related to student smoking. In addition, teacher likelihood of intervening showed a modest association with teacher smoking status, with current smokers generally indicating being the least likely to intervene for student possession or use of cigarettes. Teacher intentions to intervene were strongly associated with the prevalence of smoking among boys but not girls. PMID- 1414569 TI - Single-sex versus coeducational environment and achievement in adolescent females. AB - For women, the nature and range of experiences during the high school years take on special significance, since it is during this period that they usually weigh their various roles and adjust their levels of aspirations accordingly. If the high school environment is successful in reducing the discrepancy between what are often viewed as conflicting roles, adolescent females may place greater emphasis on achievement. It is within this context that the present paper explored the differential benefits of single-sex and coeducational schooling. The issue explored is not whether one is preferable for females; rather, the concern here is how each of these settings influences both achievement and personal fulfillment. PMID- 1414570 TI - Relationship between peer status and health behaviors. AB - Over the past decade, univariate studies have identified peer-rated popularity/sociability as a correlate of individual health practices (e.g., alcohol and drug use, exercise habits). Yet, the relationship between multiple health habits and broader social competencies rarely has been systematically examined. Accordingly, using a multivariate approach, the present study investigated the relative influence of background characteristics (i.e., age, gender, race, family type, and socioeconomic status) and peer status on health related behaviors (i.e., physical activity, eating habits, smoking, alcohol use, and stress-related behaviors) in 589 junior high school students (ages 11-13). In this sample, peer popularity provided no significant increment in the prediction of health habits over and above the effects explained by demographics. These results are consistent with current perspectives on health and interpersonal behaviors, and have important practical implications for the initiation and maintenance of healthful and risky practices in the natural environment. PMID- 1414571 TI - The cognitive and social-emotional correlates of color deficiency in children: a literature review and analysis. AB - Although color deficiency is a prevalent problem in childhood, little is known about the cognitive and social-emotional variables linked to this visual deficit. A review of the literature revealed just seven empirical articles designed to explore the psychological functioning of color-deficient children, with the results yielding contradictory findings. An analysis of the literature indicated that the equivocal nature of past research may be due to an inadequate rationale explaining what outcome variables should be tied to color deficiency. This weakness can be remedied, and as a means toward that end, specific investigative recommendations are made to provide a more valid theoretical link between color deficiency and selected cognitive and social-emotional variables. PMID- 1414572 TI - Predictors of adolescent female decision making regarding contraceptive usage. AB - The relationship of cognitive capacity, cognitive egocentrism, and experience factors to decision making in a contraceptive usage problem was examined. Fifty sexually active, unmarried females, ages 14-19, served as subjects. Using correlational, regression, and canonical correlational analyses, cognitive capacity and cognitive egocentrism variables, not experience with contraceptives, were found to be significantly related to, and predictive of, five of seven decision-making variables. Forty-one percent of the variance was accounted for in predicting the canonical decision-making variable. The implications of these results for future research are discussed. PMID- 1414573 TI - The effect of free or reduced-price lunches on the self-esteem of middle school students. AB - This study proposed to determine whether 52 middle school students who received free or reduced-price meals suffered lower general or area-specific self-esteem than did 52 sixth-, seventh-, and eighth-grade students who did not receive such benefits. It further sought to determine whether self-esteem varied according to grade level. Using the Piers-Harris Children's Self-Concept Scale, no significant differences were found for either group at any grade level for general or area specific self-esteem. Interpersonal process resources, the use of a checklist, short-term relief, defensiveness, and external forces are considered as possible explanations. PMID- 1414574 TI - Is parental divorce a critical stressor for young adolescents? Grade point average as a case in point. AB - Previous studies have shown parental divorce to be associated with poor functioning of children and adolescents. Almost all of the studies attempting to delineate these effects, and to shed light on the differences between boys and girls, have limited data collection to postdivorce. This practice has left a void in the picture of divorce--specifically in the area of predivorce effects. The purpose of the present study was to examine academic functioning of young adolescents with respect to both pre- and postdivorce effects. Fifty-eight young adolescents (29 from families which subsequently divorced and 29 from families which remained intact) were studied. Results indicated that boys from subsequently divorcing homes had significantly poorer academic functioning prior to their parents' divorce than did boys whose families remained intact and girls whose parents divorced. Differentially, girls from subsequently divorcing families showed a decline in academic functioning which began prior to divorce and continued beyond the time of divorce. Possible explanations for these gender differences are explored, and the importance of examining predivorce effects is addressed. PMID- 1414575 TI - A profile of young adolescents attending a teen family planning clinic. AB - The purpose of this study was to assess the client records of adolescents attending a teen family planning clinic to determine the reported episodes of sexually transmitted diseases, sexual abuse, alcohol and drug use, and other dysfunctional situations in the family. In addition, information about the initiation of sexual activity and sexual partners was assessed in the record review. Data were obtained from a county health department located in a metropolitan area of a southeastern state. A review of the records of 183 adolescents 15 years of age or younger provided information on ethnicity, grade in school, and assessment data from the clinic interviews and exams. Twenty-five clients said they were not sexually active when they came to the family planning clinic for the first time, and were brought to the clinic by a parent (usually the mother). Those clients who came without parents said they were sexually active. Forty-one percent had their first sexual experience between 12 and 13 years of age, 18% between the ages of 14 and 15, and the remainder before the age of 12. While over 7% specifically stated that they had been sexually abused or raped, an additional 19% described situations in the home or exhibited symptoms associated with a history of sexual abuse. Eleven percent had a history of two to three different sexually transmitted diseases, and 26% had three or more diseases. Seventy-two percent indicated that there was conflict in the home; several had left home because of abuse. Fourteen percent admitted using drugs, mostly cocaine or marijuana, and 17% reported that they used alcohol at least occasionally. PMID- 1414576 TI - Developmental profiles of adolescents and young adults choosing abortion: stage sequence, decalage, and implications for policy. AB - Three groups of unmarried females (ages 12-14, 17-19, and 23-25) electing to have an abortion in the first trimester of their first pregnancy were administered the Washington University Sentence Completion Test, the Rest Defining Issues Test, and a moral judgment interview of their reasons for choosing an abortion. Results indicated that there were clear developmental differences between the youngest group and the two older groups on the general measures of ego development and principled moral reasoning, as theory would have predicted. There were, however, no major differences across the three groups on the level of reasoning which directly assessed the specific decision concerning abortion. Further, all three groups were assessed at the self-protective level characterized by Stage 2 reasons of financial consequences and the need to rely exclusively on one's own self in such a difficult dilemma. These findings and developmental profiles are compared to national base rates, and the possible implications of apparent decalage, or discrepancy between the general stage assessments and the specific assessment on abortion, are discussed. In addition, the similarity between the older group of adolescents and the young adults was examined, particularly in light of the current controversy over mandatory parental consent. PMID- 1414577 TI - The effects of gender, race, religion, and political orientation on the sex role attitudes of college freshmen. AB - Freshmen (N = 556) at a large eastern private university were administered a questionnaire during the first week of classes. A social learning perspective was used to examine the effects of gender, race (Asian, black, and white), religion (Catholic, Jewish, and Protestant), and political orientation (liberal and conservative) on four areas of sex role ideology--traditional attitudes toward female sexuality, justification of male dominance, negative attitudes toward homosexuality, and attitudes toward feminism. Although all four independent variables produced a significant effect on at least one measure of sex role ideology, religion and political orientation produced significant differences on all four sex role measures. Liberals as compared to conservatives and Jews as compared to Protestants were less traditional in their attitudes toward female sexuality, less accepting of male dominance and negative attitudes toward homosexuality, and more accepting of feminist attitudes. The results support the view that entering freshmen have established sex role belief systems that tend to be organized around constellations of traditional/conservative versus egalitarian/liberal attitudes. PMID- 1414578 TI - Temperament and self-esteem in late adolescence. AB - The purpose of this study was to investigate the relationship between temperament and self-esteem (or social competence) among late adolescents. The Dimensions of Temperament Scale and the Short Form of the Texas Social Behavior Inventory were administered to 186 students. It was found that Adaptability, Attention/Distractibility, and Reactivity all showed significant correlations with self-esteem. An interactive framework suggested that temperament may mediate how each individual perceives and experiences social demands and constraints, thereby influencing the level of positive regard and success during development. PMID- 1414579 TI - Demographic, clinical, and personality variables associated with male prostitution by choice. AB - This research compared demographic, clinical and personality variables in a sample of 15 male prostitutes and 15 nonprostitutes from the same cohort. Unlike previous samples of male prostitutes, these young men specifically reported that they were involved by choice, primarily to earn extra money. Significant findings included heavier drug and alcohol use, more limited vocational success and aspirations, and greater alcohol use among family members of male prostitutes. Male prostitutes were also more likely to identify themselves as drug or alcohol addicted. No significant differences were found in personality characteristics between the two groups, although there was limited support for the hypothesis that male prostitutes are more antisocial. PMID- 1414580 TI - Adolescent self-perception as a function of vision loss. AB - The potential effect of vision loss on adolescents' self-perception has been the subject of limited research. Several previous studies have failed to shed much light on this relationship. This study, utilizing a sample of adolescents with visual problems and a comparison sample with normal vision, found significant differences in dimensions of perceived self-concept between these groups. Some possible interpretations of these results are offered. The need for new research in this field of inquiry is emphasized. PMID- 1414581 TI - An evaluation of parental assessment of the Big Brothers/Big Sisters program in New York City. AB - This study used a self-report survey to assess parents' impressions of the impact of the Big Brothers/Big Sisters program on their children. Parents rated program success on each of seven outcome variables (school attendance, grades, getting along with family members, getting along with friends, self-esteem, staying out of trouble, and being more responsible), and two program variables (frequency of contact and length of time in program). While children were rated by their parents as benefiting significantly from the program, children's frequency of contact did not have a significant effect on the outcome measures. However, a trend of increased success with greater time spent in the program was found. Frequency of contact between parents and Big Brothers/Big Sisters was positively correlated with reported success. PMID- 1414582 TI - Holistic attitudes of high school students toward themselves and their school experiences. AB - This study was based on an analysis of essays written by 47 teacher education students in response to the question, "If you could live your high school days over again, what, if anything, would you change?" The responses were organized into 20 different categories and tabulated according to students' age and sex. In retrospect, 38% of these students would have improved their attitude toward high school. Thirty-six percent indicated that high school was a positive experience, though this attitude was often unrelated to academic achievement. The responses strongly suggest that for many high school students, general attitude toward school affects achievement more than do attitudes toward specific school characteristics. PMID- 1414583 TI - The validity and devolution of a concept: student alienation. AB - This study examined the correspondence between conceptual and empirical dimensions of student alienation. Responses from 2,056 secondary school students were analyzed using a multivariate technique, smallest space analysis. Except for a few items, there was a basic correspondence between a multidimensional conceptualization of alienation and empirical dimensions articulated by students. Such a correspondence for both intermediate and high school students serves to strengthen confidence in the concept of multidimensional alienation specific to the school context. PMID- 1414584 TI - 8th annual meeting, Society for the Advancement of Contraception. Barcelona, Spain, October 28-31, 1992. Abstracts. PMID- 1414585 TI - Immunomodulatory drugs of relevance to the management of microbial infections. PMID- 1414586 TI - Cytokine activation of killer cells in mycobacterial immunity. AB - Mycobacterium avium-intracellulare (MAI) is an ubiquitous soil contaminant that rarely causes disseminated disease in adults, regardless of immunological status. In AIDS patients, however, this microorganism invades virtually every tissue and organ, and most conventional chemotherapeutic agents are usually ineffective against MAI. We report here that monocytes, in which MAI has established an intracellular parasitic stage, appear to be under the control of natural killer (NK) cells. Autologous large granular lymphocytes (LGL), purified from human peripheral blood mononuclear cells (PBMC), were capable of efficiently lysing MAI infected monocytes in a 5 hr 51Cr-release assay. More importantly, interleukin 2 (IL-2) was able to activate the LGL to a high degree of lysis of infected monocytes. Additionally, 3 to 4 days of incubation of LGL with MAI resulted in the induction of killer cells capable of killing bacterially-infected monocytes, as well as tumor cells. Northern blot analysis of RNA from MAI-stimulated LGL revealed specific messages for both IL-2 receptor proteins (p55 and p70). Thus, MAI can directly activate killer cells, which may therefore play a role in containment of MAI infection by lysis of parasitized monocytes before the bacteria can multiply and spread to other sites. PMID- 1414587 TI - T cell-monocyte interactions induced by Listeria monocytogenes. PMID- 1414588 TI - Recent thoughts on the immunotherapy of infectious diseases including HIV infection. PMID- 1414589 TI - "Inverse" effects of cortisone in experimental infection of mice. AB - Hydrocortisone (HC) ameliorated the course of experimental infection with E. coli given intraperitoneally. In experiments with Staphylococcus aureus and treatment with endotoxin on the day of infection, HC had also a beneficial effect, however only when LPS was injected intraperitoneally and bacteria intravenously. With the footpad swelling reaction as a model for cellular immunity it could be shown that HC alone reduced the reactivity by 75 per cent. Under endotoxin treatment, however, HC induced further inhibition when LPS was given intraperitoneally the day of sensitization but changing to a stimulatory effect when LPS was given two days later. In case of intravenous application of LPS, HC had no effect. PMID- 1414590 TI - Bacterial cell surface biological response modifiers and their synthetic counterparts. PMID- 1414591 TI - Determination of the antiinfectious activity of RU 41740 (Biostim) as an example of an immunomodulator. AB - Evaluation of the anti-infectious activity of an immunomodulator performed either in vitro or in vivo in animals as in humans must answer three questions: what are the targets? what models should be used to study the mechanism of action? what methodology should be selected for the assessment of therapeutic benefit? In the case of RU 41470 (Biostim), an immunomodulator with a known structure and of biological origin affects immunocompetent cells and two essential mediators: II1 and CSF. Because of multiple interactions between anti-infectious, anti inflammatory and anti-allergic responses, as well as the pleiotropism of mediators, there exists no absolute predictive index of activity in vivo and, independently of models of immune deficiency, experimental infections are a particularly useful pharmacological model for study of the anti-infectious activity of any immunomodulator. In this model, RU 41470 tested by oral, intraperitoneal and aerosol administration, proved to be active regardless of the type of infectious agent for extracellular bacteria, intracellular bacteria, viruses or yeasts. Because of special local features of anti-infectious defences (pulmonary, cutaneous), the target organ must be identified when studying mechanism of action. RU 41740 stimulates the metabolic activities of alveolar macrophage and the target organ is the respiratory tract. From a clinical pharmacology standpoint, stimulation of different immune components has been investigated with RU 41470 at different dosages, using double-blind versus placebo designs. Target pathology, regardless of severity, includes a risk of infection and the existence of an immunological deficiency. Chronic bronchitis is a reference pathology since patients are subject to episodes of infection, resulting in acute decompensation and contributing to worsening of the ventilatory obstructive disorder. Clinical efficacy in terms of anti-infectious prophylaxis must be evaluated by a strict methodological approach: randomized double-blind placebo-controlled trials with prolonged follow-up. RU 41470 is effective in prophylaxis of respiratory infections in chronic bronchitis (reduction in the number of respiratory infections, their duration and in antibiotic consumption) and in prophylaxis of respiratory tract infections in children over one year old. Clinicians faced with the perplexity of the mechanism of action of immunomodulators and their number are preoccupied above all by the response which such an anti-infectious immunomodulator can offer in a context of clinical reality.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1414592 TI - MDP derivatives and resistance to bacterial infections in mice. PMID- 1414593 TI - Therapeutic and prophylactic effects of romurtide against experimental animal infections. PMID- 1414594 TI - Enhancement of host resistance to opportunistic infections by ubenimex (bestatin). AB - Ubenimex is a low molecular biological response modifier (BRM) which has been demonstrated to have antitumor and immunomodulatory activities. In this study, the effect of ubenimex on infection with Candida albicans was investigated in normal and immunosuppressed mice, and it showed a prophylactic effect. In normal mice, ubenimex prolonged survival time in a dose-dependent manner. In immunosuppressed mice treated with cyclophosphamide 4 days before infection, ubenimex at 5 mg/kg for 5 days significantly increased the number of survivors. Significant improvement in peritoneal leukocyte counts and in function of neutrophils including phagocytosis and release of activated oxygen was observed in ubenimex-treated mice. These results indicate that ubenimex is a potent BRM for prevention against opportunistic infections. PMID- 1414595 TI - Potentiation of host resistance against microbial infections by lentinan and its related polysaccharides. PMID- 1414596 TI - Cytokines and anti-fungal immunity. AB - In summary, we have defined a unique host resistance circuit that has not previously been investigated. For the host control of an opportunistic fungal pathogen such as C. albicans, we have definitive evidence to indicate that LGL can respond to C. albicans by producing key cytokines, i.e. TNF, IFNg, and GMCSF, to activate neutrophil function against C. albicans. The cytokine-producing LGL differs from the spontaneous tumoricidal LGL by being DR+; otherwise other markers are identical, i.e., CD2(+)-CD16+CD4-CD8-CD15-. From the point of view of the neutrophils, they can respond to these cytokines readily within 2 hr of activation and may utilize any of the 3 antifungal pathways, i.e., oxidative radical production, enzyme degranulation, and lactoferrin release, to control Candida. It is of importance to note that TNF and GMCSF have also been shown to have chemotactic properties on neutrophils (27,28). Thus, the cytokines produced by LGL may have bifunctional roles for PMN, in not only activating them but in mobilizing them to the site of fungal invasion. In addition, we have defined that C. albicans as well as the bacterial polysaccharide, LPS, can activate PMN to produce TNF. Since TNF is a neutrophil activating factor, this implies that neutrophils may self-regulate function in an autocrine manner or utilize released TNF to recruit neighboring PMN. The possibility exists that other cytokines may also be produced by neutrophils when activated with C. albicans. Future studies should indicate the true role of neutrophils in host resistance to infection and may lead to a new identity for neutrophils as an active participant in the afferent phase of the immune response rather than an end effector cell population, waiting for outside signals to mobilize and activate them. PMID- 1414597 TI - Cryptococcal immunity and immunostimulation. PMID- 1414598 TI - Antiviral and adjuvant activity of immunomodulator adamantylamide dipeptide. PMID- 1414599 TI - Immunomodulation by medicinal plants. PMID- 1414600 TI - Immunomodulating effects of polysaccharides from medicinal plants. PMID- 1414601 TI - Effects of medicinal plants on hemopoietic cells. AB - It has been found that Juzentaihoto (TJ-48), one of the traditional Japanese kampo (herbal) medicines, improves the general condition of cancer patients receiving chemotherapy and radiation therapy. We analyze how TJ-48 elicits such effect, and show that oral administration of TJ-48 accelerates recovery from hemopoietic injury induced by radiation and the anti-cancer drug mitomycin C. The effects are found to be due to its stimulation of spleen colony-forming units. Based on the present findings, we propose that the administration of TJ-48 should be of benefit to patients receiving chemotherapy, radiation therapy or bone marrow transplantation. PMID- 1414603 TI - Biological response modifiers in infectious diseases: prospectives for the future. PMID- 1414602 TI - Multiple immunological functions of extracts from the cone of Japanese white pine, Pinus parviflora Sieb. et Zucc. PMID- 1414605 TI - Bacterial protein-LPS complexes and immunomodulation. PMID- 1414604 TI - Immunomodulation of C3H/HeJ cells by endotoxin associated protein and lipopolysaccharide endotoxin. AB - Protein kinase C plays a vital role in the activation of C3H/HeJ B lymphocytes by endotoxin associated protein; however, it is unlikely that G proteins are involved in the early signals stimulated by EP. On the other hand, LPS suppresses C3H/HeJ B cell DNA synthesis induced by EP which may be the result of PKC down regulation. LPS inhibits C3H/HeJ B cells from progressing through the G1 phase of the cell cycle blocking RNA synthesis within the first 12 hr after the cells are stimulated. Finally, this inhibition extends to activation of the arachidonic acid metabolism in C3H/HeJ macrophages and T cell proliferation to a limited extent. PMID- 1414606 TI - Suppression of antibody forming cells by lipid A analogs. PMID- 1414607 TI - BRM activities of low-toxic Bordetella pertussis lipopolysaccharides. AB - A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity. PMID- 1414608 TI - Interleukin-2 and the regulation of activated macrophage cytotoxic activities. PMID- 1414609 TI - Protective effects of cytokines in murine Salmonella. PMID- 1414610 TI - Legionella pneumophila infection and cytokine production. PMID- 1414611 TI - Tourette syndrome: genetics, neurobiology, and treatment. PMID- 1414613 TI - Self-injurious behavior and Tourette syndrome. PMID- 1414612 TI - The natural history of Tourette syndrome. PMID- 1414614 TI - Immunohistochemical study of the basal ganglia in normal and parkinsonian monkeys. PMID- 1414615 TI - Postmortem analysis of subcortical monoamines and amino acids in Tourette syndrome. PMID- 1414616 TI - Neurochemical analysis of postmortem cortical and striatal brain tissue in patients with Tourette syndrome. PMID- 1414617 TI - Basal ganglia peptidergic staining in Tourette syndrome. A follow-up study. PMID- 1414618 TI - Pathogenesis of Tourette syndrome. Clues from the clinical phenotype and natural history. PMID- 1414619 TI - Issues in genetic linkage studies of Tourette syndrome. Phenotypic spectrum and genetic model parameters. PMID- 1414620 TI - Tourette symptoms in 161 related family members. PMID- 1414621 TI - Genetic study on Tourette syndrome in The Netherlands. PMID- 1414622 TI - Linkage studies in 16 St. Louis families. Present status and pursuit of an adjunct strategy. PMID- 1414623 TI - Alternative hypotheses on the inheritance of Tourette syndrome. PMID- 1414624 TI - Structural imaging in Tourette syndrome. PMID- 1414625 TI - SPECT imaging of cerebral blood flow in Tourette syndrome. PMID- 1414626 TI - Functional neuroanatomy of Tourette syndrome. Limbic-motor interactions studied with FDG PET. PMID- 1414627 TI - PET studies on the integrity of the pre and postsynaptic dopaminergic system in Tourette syndrome. PMID- 1414628 TI - Positron emission tomography evaluation of dopamine D-2 receptors in adults with Tourette syndrome. PMID- 1414630 TI - Clinical phenomenology of tic disorders selected aspects. PMID- 1414629 TI - Clonidine and clonazepam in Tourette syndrome. PMID- 1414631 TI - Neuroendocrine and behavioral effects of naloxone in Tourette syndrome. PMID- 1414632 TI - Therapeutics of Tourette syndrome. New medication approaches. PMID- 1414633 TI - Methylphenidate in hyperactive boys with comorbid tic disorder. I. Clinic evaluations. PMID- 1414634 TI - Psychopharmacology of obsessive-compulsive disorder in Tourette syndrome. PMID- 1414635 TI - Effects of foods on the brain. Possible implications for understanding and treating Tourette syndrome. PMID- 1414636 TI - Is there a role for megavitamin therapy in the treatment of attention deficit hyperactivity disorder? PMID- 1414637 TI - Educational management of children with Tourette syndrome. PMID- 1414638 TI - The family in Tourette syndrome. PMID- 1414639 TI - Social adaptation of Tourette syndrome families in Japan. PMID- 1414640 TI - Tourette syndrome and obsessive-compulsive disorder. An analysis of associated phenomena. PMID- 1414641 TI - Behavior therapy for obsessive-compulsive disorder and trichotillomania. Implications for Tourette syndrome. PMID- 1414642 TI - Tourette syndrome. Extending basic research to clinical care. PMID- 1414643 TI - Methodology of epidemiological studies of tic disorders and comorbid psychopathology. PMID- 1414644 TI - Psychosocial factors in Tourette syndrome. PMID- 1414646 TI - Diagnosis and classification of tics and Tourette syndrome. PMID- 1414645 TI - A population-based epidemiological study of Tourette syndrome among adolescents in Israel. PMID- 1414647 TI - Tourette syndrome in a special education population. Hypotheses. PMID- 1414648 TI - Tourette syndrome and obsessive-compulsive disorder. PMID- 1414649 TI - Comorbidity, Tourette syndrome, and anxiety disorders. PMID- 1414650 TI - Direct approach to the difficult anterior neck region. AB - This article presents an alternative method to correct the sagging neck with a local dermolipectomy and median platysma duplication. The technique is recommended mainly for the older patient with redundant skin and fat in that region and who, for some reason, does not want to undergo a facelift. PMID- 1414651 TI - Hypoplasia of the lower medial quadrant of the breast. AB - A corrective surgical technique is described for a newly defined deformity: hypoplasia of the lower medial quadrant of the breast. It involves reducing the usually enlarged nipple-areola complex and reshaping the breast by turning a glandular pedicled flap from the fairly large upper two quadrants on a medial base into the underdeveloped site of the medial lower quadrant. The method proved uniformly successful in 11 cases and 17 breasts involved. PMID- 1414652 TI - Ultrasonic liposculpturing. AB - The author describes a revolutionary body contouring technique based on the surgical use of ultrasonic energy. It allows the selective destruction of only excess adipose tissue. The technique is based on three fundamental steps: (1) preparation of the areas to be treated with a large infiltration of a special solution, (2) treatment of the areas with ultrasonic energy through special titanium probes, (3) manual remodeling of the treated areas to eliminate the fluid from the bursted adipocytes (fatty acids). The advantages of this new technique are selective destruction of just the undesired tissues, elimination of the fluid from the adipose tissues, and the possibility of a real "lifting" of the skin of the treated areas, and a reduction of physical strain on the surgeon. The author has already treated more than 280 patients with excellent results and without contraindications or undesired side effects. The fundamental steps of ultrasonic liposculpturing, including a description of the physical principles on which the technique is based, are presented. PMID- 1414653 TI - Influence of suction-assisted lipectomy on coagulation. AB - Suction-assisted lipectomy is the most commonly performed surgical aesthetic procedure in North America today. The procedure is not without significant morbidity, as death as well as serious nonfatal complications have been reported. Thromboembolic disease as a complicating factor of various types of surgical procedures and trauma has been well documented in the literature. Stasis, injury, and hypercoagulation--the limbs of Virchow's triad--contribute to predisposition for morbidity. The effects of stasis and injury are experienced with most operative procedures. We questioned whether suction-assisted lipectomy, in the appropriately selected and managed patient, would demonstrate a predisposition toward a hypercoagulable state and subsequent thromboembolic disease. In our group of ten female patients who underwent large-volume liposuction, a carefully selected assay of hematological factors demonstrated alterations consistent with a controlled response to tissue injury, but did not demonstrate a predisposition to a hypercoagulable state or subsequent increased risk of thromboembolic sequelae. PMID- 1414654 TI - External skin excision in the sebaceous nose and supratip deformity. AB - Some sebaceous noses cannot be properly reduced in size because of redundant skin. After standard rhinoplasty some noses develop a supratip deformity that recurs even after subcutaneous removal of the scar tissue. These noses can be corrected only by wedge-shaped skin excision. Most patients much prefer a pleasantly shaped nose, even at the cost of a midline scar on the nose. Most surgeons are hesitant to add scars to the face. However, the vast experience with wounds following accidents, tumor excisions, or corrections of malformations has shown that generally scar formation on the nose is inconspicuous. Nineteen patients were treated successfully by skin excision at the time of primary rhinoplasty or by a second operation. PMID- 1414655 TI - Local anesthesia in reduction mastoplasty for out-patient surgery. AB - To perform a breast reduction under local anesthesia we need a large amount of anesthetic with lasting effects. For this I use a solution of 25 cc of lidocaine, 25 cc of bupivacaine, and 1 cc of epinephrine in 350 cc of saline solution. The bupivacaine allows a 4-6-hour operation. Once the breast is infiltrated, a great amount of anesthetic is lost in the incision, in the dissection, and in the resected tissue. Thus, a low dose remains subcutaneously to be metabolized by the liver. The serum lidocaine levels are low during these operations, as demonstrated by fluorescence polarization immunoassay. Under analgesic sedation the submammary sulcus and the retroglandular space are infiltrated, blocking the perforants of the intercostal nerves, under the areola, beneath the skin where the incision is made and where the areola is placed. This procedure has been applied to many techniques of breast reduction by modifying the infiltration under the incision lines. For hypertrophy up to 1000 g, 200-300 cc of anesthetic solution is used for both breasts at one stage, while for gigantomastia, about 400 cc of anesthetic is used, infiltrating and reducing one after the other. As the blood loss is minimal and the recovery very fast, with an appropriate adhesive bandage and a "soutien," the patient could be discharged in the afternoon. Our experience includes 94 reduction mastoplasties with local anesthesia, and also 74 other mastoplasties with equally good results. There were no patient complaints and, in general, they felt very comfortable, awakening without pain or side effects. PMID- 1414656 TI - Tissue suction of the male and female breast. AB - Liposuction has been used either alone or combined with resection for the correction of male and female breast deformities. The majority of the 32 patients in our study were treated for gynecomastia (69%). Other indications were Madelung's disease, gender dysphoria, asymmetry, hypertrophy, postburn and postreconstruction deformities. In 54% of the gynecomastia cases, suction alone gave a satisfactory result. In all but one male patient suction permitted us to avoid incisions other than periareolar incisions. Thirteen aspirates from gynecomastias and three glands resected secondarily after suction were examined histologically. All aspirates included glandular tissue. We conclude that breast tissue is accessible to the suction cannula, and that this is a valuable tool for correcting gynecomastia and for use in many aesthetic procedures on female patients. PMID- 1414657 TI - Male reduction mammoplasty in serious gynecomastias. AB - This article is a report on long-term followup of a total of 44 serious gynecomastia cases in the stages I-III (according to Deutinger). The treatment consisted of either a semicircular incision and subcutaneous mastectomy or a superiorly or an inferiorly based nipple transposition while performing male reduction mammoplasty. Aesthetically pleasing results could be obtained by a periareolar approach and mastectomy. This inconspicuous procedure is feasible even in massive gynecomastia cases (stage III) or in cases of male breast asymmetry. On the other hand, all cases with breast reduction plasty and nipple transposition resulted in wing-shaped, mainly broad scars, and subjectively unfavorable results. Consequently, we favor the semicircular approach in male reduction mammoplasty in treating serious gynecomastias. With regard to possible male breast cancer etiology, the histological specimen of the mammary gland in gynecomastia is excised prior to any additional liposuction for supplementary body contouring. PMID- 1414658 TI - Inferior pedicle reduction technique for larger forms of gynecomastia. AB - The treatment of larger types of gynecomastia is significantly different than that of less severe gynecomastias. Special concerns of the former include areola enlargement, nipple-areola ptosis, and redundant skin. Many procedures have been described to address these issues, none of which is completely satisfactory; these are reviewed here. Unsatisfactory results may be due to residual breast hypertrophy, skin redundancy, complications related to nipple-areola placement, form and viability, and cosmetically unacceptable scars. We describe a new technique that uses an inferior pedicle to reposition the nipple-areola complex and to maintain its neurovascular integrity and form. A superiorly based chest wall flap in conjunction with suction-assisted lipectomy maximizes chest wall contour. There are no breast mound scars, only a periareolar and inframammary scar. PMID- 1414659 TI - Periareolar mastopexy with mammary implants. AB - We present our experience with using a periareolar mastopexy technique combined with prosthesis implantation to correct mammary ptosis, misplaced areolas, and tuberous hypoplastic breasts. We draw a circle around the areola and deepidermize the skin between them. We enter the glandular tissue and introduce the implant in a submuscular pocket. A purse string suture of nonabsorbable material is used to gather the excess skin. Results were satisfactory in all cases. During the immediate postoperative weeks the shape was flatter and protruded less, but a progressive correction was observed. The tuberous breast could be released and reshaped adequately. Misplaced areolas can also be replaced correctly by drawing the periareolar circle and ellipse in eccentric forms. This technique does not allow great elevation of the areola (no more than 4-5 cm), but it is good and safe for correcting minor to moderate ptosis combined with volume augmentation. PMID- 1414660 TI - The use of leeches for treatment of venous congestion of the nipple following breast surgery. AB - The medicinal leech, Hirudo medicinalis, played a central role in the evolution of medieval and folk medicine. Today, for the first time in history, the leech actually has a real and valuable purpose in medicine as a useful adjunct for the plastic surgeon: It provides relief of venous congestion. For over 2000 years, leeches were needlessly applied for a multitude of maladies as an adjunct to blood-letting. Their use in Europe peaked between 1830 and 1850, however, shortages led to a subsequent decline in leech application. Today there is a real clinical use for leeches which had led to a resurgence in their use in plastic surgery. Plastic surgeons use leeches in microsurgery to salvage congested flaps, whose viability is uncertain due to venous congestion. We present our experience with two patients where leeches were used to treat isolated venous engorgement of the nipple following breast surgery. Leech therapy is painless, well tolerated, and does not result in significant scarring. Prompt initiation of treatment is mandatory and produces dramatic resolution of venous congestion. PMID- 1414661 TI - Mandibular angle implants. AB - A new type of implant designed to increase the angle of the mandible in three dimensions is described. Made of silicone and shaped like a saddle, this implant makes the technique of implantation relatively simple, and its versatility makes it a desirable addition to the tools for skeletal framework reconstruction of the face. The satisfaction rate has been high and the complications easy to manage. The surgical technique consists of an intraoral incision and the development of a subperiosteal pocket at the mandibular angle area, often performed under local anesthesia. PMID- 1414662 TI - Infracture technique for the zygomatic body and arch reduction. AB - In the Orient, prominent malar regions are considered unaesthetic and the majority of women with a prominent malar want to reduce the zygoma. Various operative procedures such as shaving or chiseling the zygomatic body or the zygomatic arch have been used for reducing malar eminence, but the zygomatic arch cannot be reduced sufficiently by these methods. By combining intraoral shaving of the zygomatic body and a new effect arch infracture technique through a temporopreauricular incision, we have obtained very satisfactory results in 19 cases and notable minimal complications over the last three years. PMID- 1414663 TI - Felman double-liposuction cannula. PMID- 1414664 TI - Cornerstones in reconstructive plastic surgery: Argentinian development of muscular, myocutaneous, and fasciocutaneous flaps. PMID- 1414665 TI - Ambulatory blood pressure monitoring. PMID- 1414666 TI - Association of age with regional cerebral oxygen utilization: a positron emission tomography study. AB - Positron emission tomography scans were performed on 14 normal subjects over the age of 50. Cerebral metabolic rate for oxygen (CMRO2) was assessed in a number of cortical and subcortical regions. There was a trend for a decrease in CMRO2 with age but this was significant only in the parietal lobe. There was a suggestion that the age/CMRO2 correlation became less strong with advancing age. CMRO2 in the occipital lobe, subcortical regions and cerebellum was not related to age. The relationship between CMRO2 and age is discussed. PMID- 1414667 TI - Factors related to long-term stay in hospital by elderly people in a Japanese city. AB - The characteristics and social backgrounds of 61 elderly patients with long hospital stays and those of 179 incapacitated elderly people living at home in a Japanese city were compared. Discriminant function analysis was performed to clarify the factors associated with long-term use of hospital beds by elderly people. In addition to this analysis, the elderly patients with long hospital stays were divided into two subgroups according to the likelihood of discharge, and these subgroups were compared in the same way. The elderly patients with long hospital stays were more likely to be women, persons with low ADL, living alone and not living with a spouse or a second generation, compared with incapacitated elderly people living at home. Analysis of the subgroups of the elderly subjects with long hospital stays showed that use of a urethral catheter and not undergoing rehabilitation were the medical factors related to difficulty of discharge, while being women, of advanced age and not having their own room at home were the non-medical factors associated with long-term occupation of hospital beds. PMID- 1414668 TI - Age-associated changes in mesenteric arteries. AB - Vascular disease increases in incidence with age and is the commonest cause of morbidity and mortality among elderly people. Hypertension is associated with hypertrophy of the arterial media. This study was designed to investigate changes in arterial structure that may occur with age independent of blood pressure. Collapsed sections of human mesenteric arteries (external diameter 2-3 mm) were measured using a semi-automatic image analysis system. There was a nonlinear increase in both the wall/lumen area ratio and the relative intimal area with age. There were no significant relationships between blood pressure and either the wall/lumen ratio or the relative intimal area. PMID- 1414669 TI - Can elderly diabetic patients co-operate with routine foot care? AB - Foot care education is widely promoted as a preventive strategy for reducing foot ulceration in diabetes. We describe a simple method of assessing the ability of elderly diabetic patients to co-operate with foot care advice. Using small self adhesive red spots, foot lesions can be simulated and patients advised and prompted to detect and inspect these 'lesions'. Nineteen young non-diabetic volunteers and three groups of 14 elderly patients were assessed: diabetic patients with a foot ulcer, diabetic patients with no history of foot ulceration and non-diabetic patients. Eleven (39%) of the diabetic patients were unable to reach their toes and remove the lesions and only 6 (14%) of all elderly patients could respond to plantar lesions. It is therefore unlikely that unsupported foot care education can be effective in reducing the morbidity of foot problems in the elderly diabetic patient. PMID- 1414671 TI - Use of drugs by non-institutionalized urban Finns born in 1904-1923 and the association of drug use with mood and self-rated health. AB - The purpose of this study was to examine the use of drugs by elderly people and to investigate its associations with various other factors. Random sampling was used to select 800 interviewees born in 1904-13 and a further 800 born in 1914 23. The average number of prescribed drugs per person was 2.2. Women used a greater number of prescribed drugs than did men; and this difference increased with age. The use of vitamins and trace elements seemed to decline with increasing age. Among women a significant association between the use of prescribed drugs and depressive symptoms was found. Women in the older age group used prescribed drugs more often than women in the younger age group. One fifth of the subjects had a greater number of drugs in simultaneous use than is generally recommended. It seems that, especially among elderly women, depression often remains undiagnosed and treatments are chiefly provided for the associated symptoms. PMID- 1414670 TI - Prevalence of biliary lithiasis in the elderly people of a small town in Sicily. AB - The aim of the present study was to determine the prevalence of biliary lithiasis (BL) and its major associated factors in the elderly people of a small town in Sicily. All inhabitants over the age of 65 were interviewed and underwent a general physical examination, blood tests and ultrasonography of the gallbladder and biliary tracts. The final group included 328 subjects (162 men and 166 women), representing 63.1% of the population asked to participate, with a mean age of 74.3 +/- 6.8 years (range 65-95). The prevalence of BL (lithiasis in progress + subjects cholecystectomized for previous calculosis) was 18.6%. No male subject had been cholecystectomized. Prevalence was higher in women than in men, but there was no progressive increase with age. There was no significant correlation between number of pregnancies and BL and there was no statistically significant difference between subjects with and without lithiasis for total cholesterol, triglycerides, HDL-cholesterol, A-I and B apoprotein values; a significant difference was found only for body weight values (p less than 0.01). Stones were more often multiple and more radiopaque than in younger subjects; specific symptoms and positive family histories were found in 22% and 18% of the study group, respectively. PMID- 1414672 TI - Sex differences in cancellous and cortical bone strength, bone mineral content and bone density. AB - The purpose of this study was to examine sex differences in cancellous and cortical bone strength, bone mineral content (BMC) and bone density of excised cadaver vertebral and phalangeal bones. The samples were age-matched. Bone strength was measured as the mechanical force required to crush or break the bones. Two parameters of bone strength were used on the vertebrae; the force at the first deviation from linearity and the mean force during the consolidation before final failure. The force at first deviation from linearity was not significantly different between the sexes, but there was a significant difference in the consolidation force. The mean men's phalangeal strength was twice that of the women's. BMC and BMC/BW of both types of bone were statistically different between the sexes. Radiographic photodensity measures on the vertebrae showed no sex differences. Cortical diameters of the finger bones were significantly greater in males. PMID- 1414674 TI - Alcohol and acute medical admission of elderly people. AB - In a prospective study of 539 consecutive elderly medical admissions (mean age 77.3 years; 275 men), 42 patients (7.8%; 36 men) were identified as alcohol abusers, 41 by an alcohol intake history and one by a positive response to the CAGE questionnaire; none was identified by laboratory screening (gamma glutamyltransferase and red cell mean corpuscular volume) alone. Thirteen admissions (2%) were alcohol-related. In alcohol abusers, 24% of admissions (n = 10; p less than 0.001) were alcohol-related. Alcohol abusers were predominantly men (86%; p less than 0.001) and independently mobile (88%; p less than 0.001), suggesting greater physical fitness. In these more active men (n = 167), the prevalence of alcohol abuse was 19.8% and 6% of admissions were alcohol-related. While the sensitivities of the CAGE questionnaire and laboratory screening were too low to be clinically useful, an alcohol intake history may allow for a significant opportunity in preventive medicine in this age group, particularly in the fitter men. PMID- 1414673 TI - The role of age in susceptibility to pneumococcal infections. AB - Whether or not age by itself increases susceptibility to pneumococcal infections separate from the effects of chronic disease is controversial. To address this issue, data collected for a retrospective cohort study of pneumococcal infections among 63 middle-aged and older veterans and 126 uninfected controls were reanalysed. Univariate analysis suggested a linear increase in risk with increasing age for patients 50 years old and older (p = 0.03). Subjects over age 80 years seemed to be at particularly high risk when compared with patients under 50 (odds ratio = 4.3, p less than 0.03). The odds of pneumococcal infection increased by an estimated factor of 1.33 (95% confidence interval = 1.03, 1.71) for each 10-year increase in age. Controlling for other risk factors did not appreciably change the point estimate of the age effect, but statistical significance was lost. This result however suggests that age has an independent association with the risk of pneumococcal infections. The potential impact of this finding on public policy urges that the association of age with the risk of pneumococcal disease be re-examined in a study of sufficient sample size to resolve the issue. PMID- 1414675 TI - Pulmonary function in gastro-oesophageal reflux disease of elderly people. AB - An effect of gastro-oesophageal reflux disease (GORD) on respiratory function was studied in elderly patients. Twenty-seven patients with, and 29 patients without, abnormal gastro-oesophageal reflux (GOR) in 24-hour pH monitoring were included in the study. Symptoms suggestive of gastrooesophageal reflux disease were recorded and spirometry was performed in all the patients. Patients with abnormal GOR had lower vital capacity (percentage of predicted value) (VC%) than those with normal pH monitoring result (92 vs 102, p = 0.032). Forced vital capacity (FVC%) and forced expiratory volume in one second (FEV1%) did not differ between these two groups. Thirty-two per cent of patients with slight and 73% of patients with moderate or severe reflux in pH monitoring had abnormal VC%, FVC%, or FEV1% (less than 80% of predicted value) at spirometry (vs 30% of patients without reflux, p = 0.039). When patients were divided according to their symptoms suggestive of GORD, lower VC%, FVC%, and FEV1% were found in patients with than in those without symptoms (87 vs 102, p = 0.0018; 76 vs 91, p = 0.0099; 80 vs 93, p = 0.0026). In conclusion, mainly a restrictive ventilatory defect was associated with GORD in elderly patients. PMID- 1414676 TI - Review: atrial fibrillation and stroke prevention. PMID- 1414677 TI - Intestinal transit and bacterial overgrowth. PMID- 1414678 TI - The selective protection afforded by ebselen against lipid peroxidation in an ROS dependent model of inflammation. AB - The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage). The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage. PMID- 1414679 TI - Comparative effects of tetrandrine and berbamine on subcutaneous air pouch inflammation induced by interleukin-1, tumour necrosis factor and platelet activating factor. AB - The effects of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine on the action of IL-1, TNF and PAF were investigated in the rat subcutaneous air pouch model of inflammation. Both compounds were equipotent in the suppression of leukocyte infiltration into air pouches induced by IL-1 and TNF, with ED50 values in the range 20-30 mg/kg/3 days. Both were also equipotent in suppression of PMN infiltration induced by PAF with ED50 values in the same range as that for IL-1 and TNF. However, tetrandrine was more potent than berbamine as a suppressant of PAF-induced MNC infiltration, but much less potent than berbamine in carageenen induced PMN infiltration. These results suggest that these bisbenzylisoquinolines may have value in the therapy of chronic inflammatory diseases where IL-1, TNF and PAF have a role in pathogenesis. PMID- 1414680 TI - RP 54745, a potential antirheumatic compound. I. Inhibitor of macrophage stimulation and interleukin-1 production. AB - RP 54745 is an amino-dithiole-one compound found to be active at micromolar concentration on the metabolism of stimulated macrophages, for example, the hexose monophosphate pathway (HMP) and the exocytosis of lysosomal enzymes. LPS induced interleukin-1 (IL-1) production by murine peritoneal macrophages was also diminished by this compound in vitro as well as in vivo. This effect was confirmed at the mRNA level; at the concentration of 3 x 10(-6) M, the IL-1 alpha and beta mRNA signals were inhibited, whereas the TNF alpha mRNA signal was only slightly lessened. These observations were confirmed in vivo, with a dose of RP 54745 of 25 mg kg-1. These results led us to consider that RP 54745 might influence certain cells and cytokines implicated in the regulation of the immune system, the disfunctioning of which can lead to inflammatory disorders or autoimmune pathologies. PMID- 1414681 TI - RP 54745, a potential antirheumatic compound. II. In vivo properties in different animal models. AB - The results obtained with RP 54745, an amino-dithiole-one compound, on stimulated macrophages, revealing inhibition of the hexose monophosphate pathway (HMP), of the exocytosis of lysosomal enzymes and of the production of interleukin-1 (IL 1), by the compound in vitro as well as in vivo, suggested that RP 5475 might influence cells and cytokines implicated in the regulation of the immune system, the disfunctioning of which can lead to inflammatory disorders or autoimmune pathologies. RP 54745 was effective at moderate oral doses (around 5 mg kg-1) in different mouse models of induced arthritis and in the MRL/lpr mice, genetically predisposed to develop an autoimmune pathology including arthritic disorders. The clinical status of the MRL mice, and several of their disturbed biochemical and immunological parameters, improved after a 3-month treatment with RP 54745. This activity of RP 54745 makes it a very attractive antirheumatic compound and a potentially effective treatment in pathologies where IL-1 production is exacerbated. PMID- 1414682 TI - Differences in proinflammatory activity of several immunomodulatory derivatives of muramyl dipeptide (MDP) with special reference to the mechanism of the MDP effects. AB - Immunomodulatory agents, muramyl dipeptide (MDP) and several of its analogues, i.e. adamantylamide dipeptide, murametide, murabutide and their glucosaminylated derivatives, were tested for edemagenic activity in rats. Given systemically in aqueous solutions, only MDP and glucosaminylated MDP, at the dose of 3 mg/kg (s.c. or p.o.), were found to produce edematous swelling of the paws. Local (intra-pad) application of MDP was more effective than the systemic one. Supernatants of macrophages, in vitro cultured in presence of MDP, caused the swelling as well. The edema was of a transient nature. After reaching the maximum severity (about 6 h after injection of MDP solution or 1 h after macrophage supernatants), it was subsiding and disappeared completely within approximately 6 days after cessation of the treatment. It was found that this type of rat paw edema is probably a prostaglandin-dependent consequence of macrophage activation. Hypotheses on the involvement of immunoregulatory cytokines, and possible chemical structure-inflammatory activity relationships have been suggested. PMID- 1414683 TI - Zinc monoglycerolate--a slow-release source of therapeutic zinc: solubilization by endogenous ligands. AB - A combination of 65Zn-tracer determinations, oxidative analyses for glycerol, and a bioassay for uncomplexed Zn2+ have shown that: (i) zinc monoglycerolate (ZMG) dissolves in aqueous salt solutions/physiological media by dissociation into zinc ions and glycerol, but the rate and extent of ZMG dissolution depend upon pH, and/or concentration and complexing efficiency of zinc-ligands; (ii) under physiological conditions certain ligands present in skin and blood (e.g. citrate, lactate, albumin, histidine, glutathione and other thiols and, to a lesser extent, amino acids) accelerate ZMG dissolution; and (iii) there is a general correlation between the conditional stability constants (pH 7.3, 25 degrees C) of zinc-ligand complexes and the ability of given ligands to (a) solubilize ZMG in vitro and (b) mask the irritancy of Zn2+ in vivo. These observations indicate a mechanism for the transformation of ZMG applied transdermally or subcutaneously, to bioactive zinc (anti-arthritic nutritional supplement, etc.). PMID- 1414684 TI - Role of the epithelium in the control of intestinal motility: implications for intestinal damage after anoxia and reoxygenation. AB - A vibration technique was used to dislocate the epithelium from the rat small intestine, in order to study the possible regulatory role of the epithelium on intestinal motility. Complete removal of the epithelium led to a slightly potentiated contraction of the longitudinal smooth muscle by the muscarinic agonist methacholine (pD2. 6.5 +/- 0.1 vs. 6.2 +/- 0.2). The maximal beta adrenergic response expressed relative to the relaxation by 0.5 mM dibutyryl cyclic AMP increased from 55.9 +/- 9.0% to 72.6 +/- 9.1% by this treatment. Efforts were made to relate these observations to the endothelium-dependent relaxation in blood vessels, but no indication was found for a similar mechanism in the small intestine. Not only mechanical dislocation can be employed to affect the mucosal layer, but also intestinal ischemia has been reported to lead to mucosal damage. In this study we mimicked ischemia by applying in vitro anoxia and subsequent reoxygenation to isolated intestinal segments. When intestinal segments are isolated and kept in physiological buffer, xanthine dehydrogenase is converted slowly to xanthine oxidase, irrespective of whether the buffer is oxygenated or not. No evidence was found for oxygen radical damage after anoxia and reoxygenation. However, the intestinal mucosa was damaged both after normoxia, and after anoxia and reoxygenation. Anoxia and subsequent reoxygenation did not affect muscarinic contraction, but slightly increased the beta-adrenergic relaxation, which partly correlates with the effects of mechanical dislocation of the epithelium. The increased sensitivity of the smooth muscle after epithelial damage might be involved in motility changes during intestinal inflammatory diseases. PMID- 1414685 TI - Effect of BW443C81, a novel opioid, on non-cholinergic bronchoconstrictor responses and neurogenic plasma extravasation in the guinea pig. AB - The novel, peripherally acting opioid peptide, BW443C81, which attenuates airway sensory nerve impulses, was examined on non-cholinergic (NC) constrictor responses in vitro and in vivo and neurogenic plasma extravasation in vivo in guinea-pig airways. Non-cholinergic contractions of guinea pig isolated bronchi, evoked by electrical field stimulation, were concentration-dependently inhibited by BW443C81 and morphine (10 nmol/1-100 mumol/l). In anaesthetised, artificially ventilated guinea pigs, frequency-related NC bronchoconstrictor responses evoked by antidromic electrical stimulation of the vagus nerves were reduced by BW443C81 (100 micrograms/kg/min i.v. infusion) and morphine (1 mg/kg i.v.). Neurogenic plasma extravasation produced by bilateral electrical vagal nerve stimulation in spontaneously breathing, anaesthetised guinea pigs was also inhibited by BW443C81 (1 mg/kg i.v.). The inhibitory effects of BW443C81 were reversed/prevented by naloxone. BW443C81 inhibits NC bronchoconstrictor responses and neurogenic plasma extravasation in guinea pig airways, consistent with its previously described mu opioid receptor-mediated inhibitory action on airway sensory nerve function. PMID- 1414686 TI - Vasoconstriction and bronchoconstriction induced by 2,5-di-(tert-butyl)1,4 benzohydroquinone, an endoplasmic reticular Ca2+-ATPase inhibitor, in isolated and perfused rat lung. AB - The microsomal Ca(2+)-ATPase inhibitor 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) induced bronchoconstriction and vasoconstriction in the isolated perfused and ventilated rat lung. These effects were accompanied by increased levels of thromboxane and prostacyclin in the effluent perfusate. The effect of tBuBHQ was inhibited by L-655,240, a thromboxane receptor antagonist, indicating thromboxane-A2-mediated bronchoconstriction and vasoconstriction. Accordingly, the cyclooxygenase inhibitor indomethacin largely blocked the effects of tBuBHQ. The involvement of a phospholipase in the generation of thromboxane A2(TXA2) was supported by dibucaine protection on tBuBHQ effects. The results from this study indicate that tBuBHQ, probably by inhibiting the microsomal Ca(2+)-ATPase, can trigger the arachidonic acid cascade leading to the formation of TXA2, which in turn causes bronchoconstriction and vasoconstriction in rat lung. PMID- 1414687 TI - Separate induction of human blood platelet aggregation or cytotoxicity by different concentrations of PAF-acether and thrombin. AB - Using decreasing concentrations of PAF-acether or thrombin, it was possible to observe on human platelets, first, aggregation, classically associated to activation, then , below a threshold, cytotoxicity towards Schistosoma mansoni larvae, proposed here as stimulation. These two activities appeared as distinct and antithetic. However, their induction might be the consequence of triggering of the same receptors with different intensity, since PAF-induced, but not thrombin-induced, cytotoxicity could be inhibited with specific PAF-antagonists BN 52021 and BN 52024 also known to inhibit PAF-induced aggregation. These results give credit to the hypothesis that haemostatic and cytotoxic properties of platelets are two distinct functions of these blood elements. PMID- 1414688 TI - Inhaled budesonide regimen enhances serotonin- and arachidonic acid-induced platelet aggregation. AB - The influence of inhaled budesonide regimen (400 micrograms x 2 for 7 days), on agonist-induced platelet aggregation and secretion, was investigated in 18 volunteers. Platelet activation induced by serotonin and arachidonic acid was significantly enhanced after budesonide, as demonstrated by an increase in aggregation velocity (Vmax) and amplitude (Amax), and in arachidonic acid-induced ATP-secretion. We found no change in platelet aggregation induced by ADP, epinephrine, and A23187. With the exception of epinephrine-induced platelet aggregation, which was inhibited by 10(-5)-10(-4) M budesonide, in vitro studies revealed no influence of 10 min budesonide preincubation (10(-9)-10(-4) M) on agonist-induced platelet activation, suggesting that the ex vivo enhancement of platelet function was mediated by secondary corticosteroid mechanisms. A tentative explanation of the increased arachidonic acid-induced platelet activation, may be a budesonide-induced stimulation of cyclooxygenase. The enhanced serotonin-induced platelet aggregation may be a reflection of exogenous corticosteroid stimulation of the 5-HT2-receptor. PMID- 1414689 TI - Rapid and sensitive detection of hydroxyl radicals formed by activated neutrophils in the presence of chelated iron: hydroxylation of deoxyguanosine to 8-hydroxydeoxyguanosine. AB - Hydroxyl radicals (OH) can react with deoxyguanosine (dG) leading to the formation of 8-hydroxydeoxyguanosine (8OHdG). In this study, this has been used to detect the hydroxyl radicals formed when human polymorphonuclear leukocytes (PMNL) are stimulated with phorbol myristate acetate (PMA) in the presence of chelated iron. Reaction mixtures containing PMNL, PMA, dG and Fe-EDTA were incubated at 37 degrees C, and the formation of 8OHdG was analysed with high performance liquid chromatography and electrochemical detection. 8OHdG formation was detected at PMA concentrations of 2 nM or higher, and half-maximal 8OHdG formation was found at around 6 nM PMA. Stimulation of 500,000 cells with 10 nM PMA for 20 min resulted in a 500 to 1000-fold increase in 8OHdG formation as compared to unstimulated cells. The 8OHdG formation decreased after addition of hydroxyl radical scavengers (sodium benzoate, dimethylsulfoxide, and mannitol) and increased after addition of platelet-activating factor (PAF), an agent known to stimulate the generation of reactive oxygen metabolites in neutrophils. These results demonstrate that hydroxylation of dG to 8OHdG can be used to determine neutrophil-generated hydroxyl radicals in different experimental systems. Since the analysis of 8OHdG is rapid, sensitive and easy, this may have wide applications in inflammation and cancer research. PMID- 1414690 TI - The pneumotoxicant paraquat potentiates IL-1 and TNF production by human mononuclear cells. AB - Interleukin 1 (IL-1) and tumor necrosis factor (TNF) have been implicated in the pathogenesis of bleomycin- and silica-induced lung damage. We have studied the effect of paraquat (PQ), a well-known pneumotoxicant, on IL-1 and TNF production by human peripheral blood mononuclear cells from different healthy donors stimulated with endotoxin. PQ (100 microM) potentiated IL-1 production (2-40 fold) and TNF production (2-18 fold). It is, therefore, possible that IL-1 and TNF are also involved in the pneumotoxic action of PQ. PMID- 1414691 TI - Biphasic regulation by dexamethasone of IL-1- and LPS-stimulated endothelial prostacyclin production. AB - Body reaction to injury comprises two major pathways: the immune response, predominantly mediated by IL-1 and other cytokines, and neuroendocrine mechanisms, resulting in an increased glucocorticoid production. Each has distinct effects on prostaglandin (PG) production, which may in turn mediate both systemic and local inflammatory responses. The interactions, if any, between the two systems on PG synthesis have not been studied. Bovine aortic endothelial cell cultures were used and prostacyclin (PGI2) production was monitored. Cells were treated with dexamethasone (Dex) 10(-6) M and IL-1 10-30 U/ml in one experiment, and lipopolysaccharide (LPS, 0.1-1.0 micrograms/ml) in another experiment, separately or in combination, for either 2 or 24 + 2 h. While Dex was without effect, IL-1 and LPS stimulated PGI2 in a concentration- and time-dependent manner. Short exposure to Dex (2 h) enhanced the stimulation by IL-1 and LPS. On the contrary, more prolonged exposure (24 + 2 h) reversed the effects of IL-1 and LPS, resulting in PGI2 levels below the baseline. A biphasic regulation by Dex was also observed with increasing concentrations of LPS. Dex was actually ineffective by itself, but it enhanced PGI2 production in combination with lower concentrations of LPS, while abolishing the influence of higher concentrations of this agonist. The data suggest that Dex may initially stimulate phospholipase A2 (PLA2) activity, while inhibiting it later. This biphasic behavior may be attributed to different concentrations of a PLA2-modulating protein, possibly lipocortin, that accumulate during exposure to Dex. PMID- 1414692 TI - Effect of prostaglandin E2 and 3-morpholinosydnonimine (SIN-1) on arachidonic acid metabolism in fMLP-stimulated rat neutrophils and on thrombin-induced human platelet aggregation. AB - The effects of prostaglandin (PG) E2 and the nitric oxide (NO) donor SIN-1 on leukotriene (LT) release from formyl-methionyl-leucyl-phenylalanine (fMLP) (100 nM)-stimulated rat peritoneal neutrophils (RPN) and on thrombin-induced aggregation of washed human platelets were investigated. Both PGE2 (1-100 nM) and SIN-1 (30-300 microM) inhibited release of LTB4 and cysteinyl-LT from RPN in a concentration-dependent manner. The combined effects of PGE2 and SIN-1 were not greater than expected by summation. On the other hand, the inhibitory effect of SIN-1 (0.5 or 1.0 microM) on platelet aggregation was potentiated by PGE2 (0.3-5 microM) in a concentration-dependent manner, while PGE2 alone in the concentrations used had only marginal effects. The results suggest differential regulation of platelet and leukocyte functions by the mediators PGE2 and NO, which could be relevant for various physiological and pathophysiological conditions. PMID- 1414693 TI - Effects of prolactin on rat paw oedema induced by different irritants. AB - Evidence suggests that prolactin (PRL) may have a role in immune function, but no data exist on the possible interference between PRL and inflammatory processes, in spite of the known correlation between inflammatory and immune reactions. In the present study the activity of prolactin on rat paw oedema was investigated. Repeated administrations of ovine PRL or a hyperprolactinaemia induced by pituitary gland graft provoked an evident increase of the inflammatory response induced by carrageenan. This effect was also present when adrenalectomised animals were used. Indomethacin completely suppressed the pro-inflammatory effect of ovine PRL; bromocriptine reduced the paw oedema, but when both bromocriptine and PRL were administered the two opposite effects seem to annual each other. Also phospholipase A2-induced paw oedema was potentiated by PRL pretreatment and inhibited by bromocriptine, whereas in dextran or serotonin-induced paw oedema both PRL and bromocriptine were ineffective. A possible involvement of prostaglandins and/or of phospholipase A2 in the pro-oedemigenic activity of PRL is suggested. PMID- 1414695 TI - [Thinking on cataract surgery and intraocular lens]. PMID- 1414694 TI - Interaction studies of tilomisole, aspirin, and naproxen in acute and chronic inflammation with assessment of gastrointestinal irritancy in the rat. AB - The effect of combination NSAID therapy of tilomisole with aspirin or naproxen was studied in rats with carrageenan-induced paw edema and established adjuvant arthritis. Inflamed paws were measured using mercury plethysmography and the arthritic paws were X-rayed to determine any bony/soft tissue changes. The gastrointestinal tract was also examined for bleeding and ulceration. Tilomisole had a less potent acute anti-inflammatory effect than aspirin or naproxen, but produced no significant gastrointestinal damage. A significant reduction in anti inflammatory activity was observed with the tilomisole/aspirin combination in acute inflammation. Only additive interactions were observed with the naproxen inhibition. In the established arthritis assay, a significant synergistic anti inflammatory response, i.e. both inhibition of paw edema and bone erosion, was also observed with the 80 and 93% tilomisole/naproxen combinations. The gastric ulcerogenic effect of the combination paralleled its increased activity. The synergism between tilomisole and naproxen in this chronic arthritic model may be due to enhanced cyclooxygenase inhibitory activity. These drug interaction studies suggest possible interactions in human clinical trials of rheumatoid arthritis. PMID- 1414696 TI - [Deterioration of amplitude of the accommodation with age and its possible restoration in the intraocular lens implanted eye]. AB - This study aimed to determine whether pseudophakia which have deteriorated amplitude of accommodation with age, i.e., presbyopia and which received implantation of refractively changeable intraocular lenses after cataract extraction are able to regain accommodative function. According surveys on aging in the literature, functional deterioration of the ciliary muscle and the zonular fiber is not so striking compared to the changes of crystalline lens material and capsule. Consequently the artificially pseudophakic eye can be expected to regain accommodative function when the crystalline lens material could be replaced by an appropriately visco-elastic material before 80 years of age when the crystalline lens capsule still retain its elasticity. PMID- 1414698 TI - [Implantation of IOLs with different diameters]. AB - The intraocular lenses (IOLs) commonly used today are 13.5 to 14 mm in diameter, and this diameter is considered by some to be unnecessarily large. The size of the crystalline lens and the diagonal width between the ciliary sulcus were measured in rabbit eyes and human eyes. Then, IOLs with a smaller diameter (12.5 mm) were evaluated after implantation into rabbit eyes. The mean diameter of the human crystalline lens was 9.6 mm and its thickness was 4.1 mm. The mean width of the ciliary sulcus was 11.1 mm. The crystalline lenses of rabbits were larger than those of humans. Decentration and posterior capsular opacification score were 0.33 mm and 0.63 in 12.5 mm IOL, and 0.47 mm and 0.61 in 14.0 mm IOL. Indicating that the result of implanting the 12.5 mm IOL was not inferior to that of implanting the conventional 14 mm IOL. The average width of the ciliary sulcus is 11.1 mm, indicating that a 12.5 mm IOL is of a sufficient size to be firmly fixed in this sulcus. In addition, a 12.5 mm IOL is considered to be safer, because larger lenses may lead to erosion or vessel compression that could induce ischemia or neovascularization. PMID- 1414697 TI - [Effects of pre-instilled mydriatics on the intraocular concentration and anti inflammatory action of topical 0.1% pranoprofen (2)--Study on multiple dosing]. AB - We studied the effects of multiple dosing and pre-instilled mydriatics (0.5% tropicamide and 0.5% phenylephrine) on the intraocular concentration and anti inflammatory action of topical 0.1% pranoprofen (PPF) in rabbit eyes. PPF was applied in a single or multiple doses: 1 to 4 times consecutively at 5-minute intervals with or without pre-instilled mydriatics. PPF concentrations in the aqueous humor increased dose-dependently. The PPF concentrations also increased dose-dependently, and reached the maximal concentration by instillation 3 times in the presence of pre-instilled mydriatics, and the concentrations were 3.4 to 5.8 times higher than those without mydriatics. The PPF concentrations in the cornea, secondary aqueous, and iris-ciliary body increased in a dose-dependent manner, and the concentrations were higher in the presence of mydriatics. PPF reduced the protein rise in the secondary aqueous and miotic responses which were seen after paracentesis. The percent inhibitions ranged from 75 to 83, but the inhibitory actions were not enhanced by increases of intraocular PPF concentrations. These data indicate that the potent anti-inflammatory actions of PPF were obtainable by a single instillation, but it might be useful to instill the drug 3 times consecutively to ensure higher intraocular drug concentrations in combination with pre-instilled mydriatics. PMID- 1414699 TI - [An experimental study of the surgical trauma on the rabbit's lens suspensory apparatus after cataract surgery]. AB - Extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (PC-IOL) implantation requires that the posterior capsule and the zonules remain sufficiently intact. To assess the surgical trauma on the lens suspensory apparatus of the enucleated rabbit eye, we developed a new fine pressure gauge that could quantitate its strength. The cornea and the iris of enucleated eyes were removed to allow clear visualization of the anterior surface of the lens to the equator. Afterwards several types of anterior capsulotomy were performed for ECCE and PC-IOL implantation. And then the lens of the pseudophakic eye was vertically pressed with the plastic rod of the fine pressure transducer, and the strength of the lens suspensory apparatus was simultaneously measured. The strength of the lens suspensory apparatus of the pseudophakic eye decreased approximately 35% compared with that of the phakic eye. Moreover the integrity of the lens capsule of animals with circular capsulorhexis with tears or linear capsulotomy decreased approximately 43% compared with that of continuous circular capsulorhexis (CCC) and also zonular rupture and vitreous loss occurred as a result of the expansion of radial tears in the anterior capsule. The present study indicates that the strength of the lens suspensory apparatus decreases with cataract surgery, suggesting that much more attention to cataract surgery is needed if the anterior capsule had radial tears. It is also suggested that CCC is the best type of anterior capsulectomy procedure. PMID- 1414700 TI - [Pathology of IOLs placed in the capsular bag of white rabbit eyes]. AB - The authors performed a histopathological study to observe the surface of IOLs placed inside the capsular bag of white rabbit eyes. While a cellular reaction to the haptics was indicated by lens epithelial cells and collagen fibers surrounding the haptics, a wound healing reaction at the anterior capsule-optic junctions was suggested by an extensive amount of spindle cells and collagen fibers. However, collagen fibers and degenerated cells on the optics could be seen only under electron microscopy. Regenerated lens fibers, lens epithelial cells, and proliferation of spindle cells were noted between the posterior side of the optics and the posterior capsules. PMID- 1414701 TI - [Retinal damage induced by visible blue and near-infrared light of an operating microscope]. AB - The authors evaluated possible hazards to the retina caused by the longer wavelength component in the illumination system of the surgical microscope. Thirty six pigmented and eleven albino rabbit eyes were exposed to blue or near infrared light for 60 minutes. Ophthalmoscopically visible light damage to the retina developed in 4 of 5 pigmented rabbit eyes after illumination at a power setting of 8 mW/cm2 for blue and 50 mW/cm2 for near-infrared light. These power settings were equivalent to those used in clinical tests. The light damage developed immediately after illumination with near-infrared light and a few days after illumination with blue light. No light damage developed in albino rabbits with near-infrared light at current power setting. The findings suggest the possibility that clinical retinal damage may develop in human eyes when exposed to near-infrared light from surgical microscopes. PMID- 1414702 TI - [The existence of vasomotor nerve in the retina of the rabbit and monkey]. AB - In the first stage of this study, peri- or intravascular unmyelinated nerve axon which was clearly different from that of the optic nerve was confirmed in the rabbit retina transmission electron microscopically. In the second stage, the correlation of these unmyelinated nerves and autonomic nerve was studied in rabbits and monkeys. For the purpose, wheat germ agglutinin horseradish peroxidase (WGA-HRP) was injected into the superior cervical ganglion. Electron microscopic observation of the retina 48 hrs after the injection of WGA-HRP showed deposit of its reaction product in the axon of the unmyelinated nerve located around the vascular wall and in the adventitia and smooth muscle cell in both rabbits and monkeys. This result clearly reveals the existence of an autonomic vasomotor in the retinal vessels at least in rabbits and monkeys. PMID- 1414703 TI - [Experimental study on earlier thrombogenic process in thrombin induced retinal venous obstruction in rabbit eye]. AB - The purpose of this study was to morphologically investigate the thrombogenic process in the early stage of retinal venous obstruction development. Venous obstruction was induced by transadventitial instillation of thrombin (5 units) given to the rabbit retinal vessels via a sclerovitreous route. The changes were studied by ophthalmoscopy, fluorescence microscopy combined with an intravenously injected gelatin fluorescein preparation technique as well as light and electron microscopy. No ophthalmoscopic change was seen within 1 hr after thrombin instillation. Three hour after thrombin instillation, focal narrowing of retinal arterioles was found with intraluminal platelet aggregation and rouleaux formation of erythrocytes. On electron microscopy, a large number of monocytes was observed in the lumina and subendothelial space of a pericytic venule having a partial endothelial defect as well as monocyte adhesion to its luminal surface. At more than 6 hrs, subendothelial thrombi were observed in the venules without any endothelial lesion while no change was observed in the arterioles, capillaries and pericytic venules. These findings suggested the possibility of participation of the arteriolar lesion in the occurrence of retinal venous obstruction and the role of endothelial lesions caused by blood stasis in subendothelial thrombogenesis. PMID- 1414704 TI - [Gene rearrangement analysis of conjunctival malignant lymphomas]. AB - Specific DNA probes for genes encoding immunoglobulins (Ig) and the T cell receptor (TCR) are useful diagnostic tools in lymphoproliferative disorders. Gene rearrangement analysis was carried out in 2 cases of conjunctival lymphoid lesions. A 36-year-old man (case 1) had a 1-year history of left conjunctival tumor. A biopsy was performed and histopathological findings showed diffuse proliferation of small lymphocytes, but monoclonality was not revealed by immunophenotypic analysis. A right conjunctival lesion developed and five months later a biopsy of the left conjunctiva was performed again. A frozen sample was analyzed and immunoglobulin heavy chain gene rearrangement was found. A 53-year old woman (case 2) had a 6-month history of bilateral conjunctival tumor. The first biopsy did not reveal monoclonality immunophenotypically. A second biopsy with a frozen specimen was analyzed and immunoglobulin heavy chain gene rearrangement was found. We diagnosed these two cases as B-cell lymphoma. We discuss the clinical value of gene rearrangement analysis as a diagnostic method for lymphoproliferative disorders. PMID- 1414705 TI - [Seasonal variation of intraocular pressure after trabeculotomy]. AB - The author reviewed the seasonal variation of intraocular pressure (IOP) in primary open angle glaucoma or late type developmental glaucoma to investigate possible relationships among seasonal variation of IOP, progression of visual field defects and the follow-up period between 53 eyes of 39 subjects with successful trabeculotomy (trabeculotomy group) and 45 eyes of 31 subjects with only medication (no operation group). IOPs in both groups were inclined to be low in summer and high in winter. Maximum seasonal variation of IOP and standard deviation of IOP during all follow-up periods which showed the degree of seasonal variation of IOP had no significant difference between the trabeculotomy group and the no operation group. These results showed that seasonal variation of IOP was not reduced even by successful trabeculotomy. The maximum seasonal variation of IOP and standard deviation of IOP had a tendency to be bigger in cases with progression of visual field defects than in cases with no progression of visual field defects, in both groups. Therefore, seasonal variation of IOP may be an important factor influencing the progression of visual field defects. PMID- 1414707 TI - [Reticular degeneration of retinal pigment epithelium]. AB - Reticular degeneration of the retinal pigment epithelium (RDRPE) was found in 33 out of 3114 files (1.06%) of fluorescein angiography. The age distribution of the cases with RDRPE showed a peak in the 8th decade, and the average age was 73 years. No statistically significant sexual tendency was observed. Eighty five percent of cases had bilateral RDRPE. The linear, incomplete polygon type was found on the nasal quadrants in patients aged 50-70 years old. The complete polygon type was found in both nasal and temporal quadrants in patients over 70 years old. RDRPE and pigment epithelium degeneration at the posterior pole were found to be concomitant manifestations. It was concluded that RDRPE initially appears on nasal quadrants as a lineal, incomplete polygon pattern and in advanced cases complete polygon pattern appears on all quadrants of the peripheral retina. PMID- 1414706 TI - [Statistical analysis of relationship between microalbuminuria and diabetic retinopathy]. AB - The relationship between microalbuminuria indicated by the logarithm of the albumin index and the stage of diabetic retinopathy was investigated using 175 diabetic subjects. The relationship and its dependence on the duration and the age of onset of diabetes were analyzed statistically with logistic regression. In younger-onset subjects, microalbuminuria was strongly related to the stage of retinopathy, but in older-onset subjects, the relationship showed to lack. For each subject, the frequency of retinopathy was predicted by the estimated probability calculated with the regression model. When the critical probability was 50%, the sensitivity and specificity were 53.1% and 76.2%, respectively. These results indicated that the regression model using the albumin index might be a useful method to predict the frequency of diabetic retinopathy even without ophthalmoscopic examination. PMID- 1414709 TI - [A caruncular oxyphilic adenoma with an appearance of apocrine type secretion]. AB - The histopathological and cytological findings of a caruncular oxyphilic adenoma (oncocytoma) in a 85 year-old male is described. The columnar or polygonal tumor cells contained numerous eosinophilic fine granules (mitochondria). They showed papillary proliferation and cyst formation. Electron microscopically, some tumor cells contained amorphous cytoplasm and small numbers of mitochondria in their apical snout, and secreted the contents in the extracellular spaces. It seemed that the tumor cells originated from the ductal epithelia in the caruncle and microscopically some cells simulated apocrine type secretion. PMID- 1414708 TI - [A case of chronic progressive external ophthalmoplegia with Oguchi's disease]. AB - A 52-year-old case of chronic external ophthalmoplegia accompanied by Oguchi's disease was reported. The patient noticed night blindness and deafness since childhood. Later he developed ocular movement limitation to all directions by the age of 40. He had 20/20 corrected visual acuity and normal anterior segment, as well as normal color vision. Goldmann's perimetry showed generalized constriction of the peripheral field. Golden tapetal reflex without dark adaptation disappeared after 4 hours of dark adaptation, i.e. Mizuo-Nakamura's phenomenon was recognized. Recovery of diminished a and b wave electroretinogram to the subnormal range was also observed after 4 hours of dark adaptation. Rod-cone interaction test revealed a monophasic adaptation, and no suppression to the cones from the rods was observed. This finding was also compatible with Oguchi's disease. ECG revealed incomplete atrio-ventricular as well as right bundle branch blocks. Neurological examination findings were entirely normal other than slight enhancement of deep tendon reflexes in the lower extremities and mixed typed difficulty of hearing. Muscle biopsy of the right medial rectus muscle revealed ragged-red fiber, suggesting mitochondrial abnormalities. Never the less the quadriceps femoris muscle biopsy specimen showed normal histological findings. This is the first case report of progressive external ophthalmoplegia associated with Oguchi's disease. Mitochondrial abnormality was confirmed only in the external ocular muscle. This case may be a variant of Kearns-Sayre syndrome. PMID- 1414710 TI - Urethroplasty of recurrent urethrocele: study of 41 cases. AB - Recurrent urethrocele is not often successfully treated surgically because, as is well known, pre-operative sterilization of the urethrocele is difficult, especially when it is very large. Furthermore the incomplete excision of the corpus callosum, because of the loss of urethral tissue this involves, often leads to post-operative fistulas and stenoses. This is why, very often, there are relapses no matter what technique is adopted. In 1978 both Juraschek and ourselves published a technique, derived from Monseur, in which the urethrocele and the corpus callosum were completely excised. The resulting loss of urethral tissue was remedied with the albuginea from the ventral surfaces of the corpora cavernosa after a 180 degrees rotation of the urethra. The results of this treatment in 41 cases of recurrent urethrocele are given in this paper. The follow-up period for the patients was from 15 to 2 years. Results have been excellent with very few complications (2 post-operative fistulas and 2 urethra stenoses). There have been no relapses. PMID- 1414711 TI - Xanthogranulomatous pyelonephritis in pelvic ectopic kidney. AB - Xanthogranulomatous pyelonephritis occurred in a pelvic ectopic kidney in a 70 year-old man. Pre-operative diagnosis was possible due to the typical appearance at CT scan of central lithiasis and multiple rounded areas of low density with enhancing rims (bear paw sign). PMID- 1414712 TI - Non functioning adrenocortical carcinoma. A rare case. AB - Adrenocortical carcinoma is a rare tumor and experience in its diagnosis and treatment is limited. We present a case of non functioning adrenocortical carcinoma in which the pre-operative diagnosis of a kidney tumor had been made and a radical nephrectomy was performed. PMID- 1414713 TI - A case of epidermoid cyst of the testis role of conservative surgery. AB - We report one case of an epidermoid cyst of the testis in a 15 year-old boy. Pre operative testicular ultrasound may help to establish the diagnosis without resorting to orchiectomy. In such a selected case local excision alone should be considered adequate without violating accepted surgical principles. PMID- 1414714 TI - Renal localisation of eustroggylous Visceralis parasite. PMID- 1414715 TI - The use of extracorporeal lithotripsy to remove calcified ureteral stents. PMID- 1414716 TI - Corporeal reconstruction and prosthetic implantation for impotence associated with non-dilatable corporeal cavernosal fibrosis. AB - Thirty patients with severe cavernosal body fibrosis, secondary to various etiologies, underwent penile prosthetic implantation with cavernosal reconstruction using Gortex grafting material. The overall success rate was 70% (21 of 30 patients). Infection was the most significant postoperative complication and required device removal in 9 patients. This operative procedure was the only option these patients had in hope of restoration of erectile function for satisfactory sexual intercourse. We continue to recommend this procedure to the highly motivated, carefully selected patient. PMID- 1414717 TI - Emergency percutaneous nephrostomy in the septic kidney. AB - From 250 upper tract obstructive uropathy cases we have studied 64 patients hospitalized with toxico-septic shock. The constant symptom was arterial hypotension. Other 3 patients with long-standing urinary infection due to lithiasis developed this dreaded complication after PNL (staghorn stones-2, pyelic stone-1). In complicated obstructive uropathy cases associated with toxico septic shock, percutaneous nephrostomy for high urinary derivation in emergency is usually made under local anaesthesia. Its aim is rapid and efficient clearance of kidney obstruction, with minimal damage for the patient; then it is followed by strong antibiotherapy associated with other reanimation and intensive care measures. There were 11 deaths. The stone generating obstructive uropathy was removed subsequently, after the improvement of biological constants and general state of the patient, under the protection of percutaneous nephrostomy. PMID- 1414718 TI - Anuria due to lithiasis associated with septic shock. AB - During 18 months 38 patients with anuria due to lithiasis were admitted in our department, 8 of them developed septic shock. Twenty eight patients were cured using different procedures and were released from the hospital with normal urinary output. Ten patients died, 6 of them from septic shock, which has a high mortality rate. Emergency restoration of urinary flow, correction of fluid and electrolyte imbalance, massive antibiotherapy may improve results. PMID- 1414719 TI - Urosepsis. Clinical aspects--therapy--results. AB - Nine cases of urosepsis registered between 1986 and 1990 are analyzed. Authors intended to find out practical conclusions which can improve the prognosis of urosepsis. Risk factors are considered advanced age, preoperative disorders (diabetes, malnutrition), preexistent end organ failure (kidney, liver, lung) and urinary infection. Early diagnosis, emergency restoration of urinary flow, suppression of primary focus of infection, intravenous antibiotherapy and energetic intensive care measures are necessary for the outcome of patients. PMID- 1414720 TI - Clinical comments on management of urosepsis in a general urological department. AB - Over a period of 6 years 192 cases of urosepsis have been recorded and managed in our urological department. In almost all cases (97%) the primary focus of infection was the urinary tract and the responsible microorganisms were Gram negative rods, in order Enterobacter, B. Proteus, E. Coli, Klebsiella and others. Clinical features were dominated by symptoms related to failure or insufficiency of end organs (fever, hypotension, oliguria, mental disorders, respiratory distress etc.). Bacteremia was diagnosed with an incidence of 66%, septic shock 12% and MSOF 20%. Negative bacteriological tests do not rule out the diagnosis of systemic infection. Risk factors are considered advanced age, uremia, diabetes, malnutrition and extensive surgery. PMID- 1414721 TI - Urodynamic findings in patients below 12 years old with different clinical types of enuresis. AB - We examined 50 children younger than 12 years old with different clinical types of enuresis. Urodynamic disorders were found in many patients. Our results indicate that the more clinical symptoms are present, the more frequently urodynamic dysfunctions are found. PMID- 1414722 TI - Sensory disorders of the lower urinary tract: urodynamic evaluation. AB - Sensory disorders of the lower urinary tract (urethral syndrome, prostatodynia, painful pelvic-perineal syndromes, trigonitis) are clinically frequent, however this diagnosis is possible only by excluding other pathologies after clinical and instrumental evaluation. The Authors report their experience in urodynamic evaluation of sensory disorders of the lower urinary tract and they discuss about the absence of a typical urodynamic pattern of sensorial pathology. PMID- 1414724 TI - A pseudotumoral edema of the urinary bladder secondary to an intramural impacted ureteral lithiasis. AB - A case of pseudotumor of the urinary bladder secondary to intramural lithiasis is reported. Computer tomography, cystoscopy of the mass and cytology suggested a malignant tumor. A transurethral biopsy from the tumor was therefore performed, but it showed tissue covered with normal transitional cell epithelium but no signs of malignancy. Pseudotumoral edema of the bladder is easily mistaken for a malignant neoplasm (1, 2, 3). PMID- 1414723 TI - Surgical extraction of a bladder stone due to a foreign body. PMID- 1414726 TI - Magnetic resonance imaging of a penile fracture. AB - A case of a penile fracture is reported. Magnetic resonance (MR) imaging clearly demonstrated the tear of the tunica albuginea. MR imaging helps us to decide the site of the skin incision. PMID- 1414725 TI - The vacuum erection device. A noninvasive treatment for impotence. AB - In 30 men we have tested the vacuum device after determining the cause of their impotence. 90% achieved penile rigidity sufficient for vaginal penetration. 10% didn't want to use it. Of the 30 men 20 (66%) reported that they used the device regularly after at least 6 months. In 4 patients the development of ecchymoses and petechiae was the reason to stop using the device. The vacuum device appears to be a safe, noninvasive and effective treatment for all causes of impotence. PMID- 1414727 TI - Leiomyosarcoma of the spermatic cord: report of a case. PMID- 1414728 TI - [Obstructive urinary tract diseases and prenatal diagnosis. Timing of surgical correction]. AB - The Authors are reviewing their experience of Obstructive Uropathies diagnosed and treated surgically in neonates, the last 8 years in their Institution. 67 cases were reviewed, in which 37 presented with ureteropelvic junction obstruction (UPJ). 13 with posterior urethral valves, 11 with primary megaureter and 6 with ureterocele. Prenatal ultrasonography allowed the diagnosis to be made in two third of the patients. UPJ is the most common obstructive uropathy observed. Posterior urethral valves the most severe because of high pulmonary and renal (dysplasia) complication rate. Surgery, when indicated, has no more complications to be expected than in general population, if oriented prophylactic measures are taken in the early peri- and postoperative period. PMID- 1414729 TI - [Aneurysm of the renal artery and its infarct complications (clinical case and literature review)]. AB - The authors are reporting the case of a 74 year old man, presenting a renal artery aneurysm. Regarding clinical aspects, medical treatment was elected. The most frequent cause of renal infarct is embolisation arising from the heart, followed by large vessels emboli that are more exceptional. Embolisation arising from the renal artery aneurysms is not very common. Unless contra-indications, surgical cure of the aneurysm is necessary, except those that are non complicated, with a diameter of less than 1.5 cm. PMID- 1414730 TI - A mysterious cyst on the corpora in a patient with ulcerative colitis. AB - A case of a man with a cystic tumor destroying the corpus cavernosum at the penile basis is described. A surgical excision was performed. The real nature and the origin of the cyst is not elucidated. PMID- 1414731 TI - Ectopic colonic epithelium of the bladder complicated by development of an adenocarcinoma. AB - A case of a female patient with an adenocarcinoma of the bladder emerging from ectopic colonic epithelium is reported. Although urothelial metaplasia in itself is not a premalignant lesion, patients with metaplasia of the bladder epithelium should be followed up very strictly since malignant degeneration has been proved to occur. PMID- 1414732 TI - Endoscopic treatment of colovesical fistula. An endoscopical approach. AB - The authors report one case of a colovesical fistula in a 70-year-old man. The treatment was transurethral resection. There has been no evidence of recurrence in more than a two-year follow-up. This procedure could be useful when surgical treatment cannot be performed. PMID- 1414733 TI - [Preliminary study of the hormonal effect on various parameters of the pelvic floor in genitally active women without hormone therapy and in menopausal women]. AB - This study proves the benefit of estrogens on the laxity, tonicity and contractility of the pelvic floor, as measured with a tonimetric instrument. The statistical hypothesis, that these three parameters are improved in genitally active women during estrogenic phase as compared to the progestative phase, as well as in menopausal women under substitutive treatment as compared to the menopausal women without hormonal treatment, is confirmed with a high degree of significance. PMID- 1414734 TI - [Treatment of prolapse using the abdominal approach]. AB - Genital prolapses are regularly constituted by multiple disorders such as primary stress incontinence anterior and posterior colpocele enterocele. All of these must be taken into account during the treatment by abdominal approach. The principles of treatment consist into a fixation of prolapse with mersilene mesh to the promontory. It could be laid on the anterior wall of the vagina and sometimes on posterior, if it's necessary. Uterus could be preserved but subtotal or total hysterectomy might be done; in this case, aseptic conditions are absolutely imperative. Vaginal section with stapling instrument and absorbable staples is useful. A colpopexy is always made. PMID- 1414735 TI - [S. Raz' method of bladder suspension and treatment of cystocele in urinary stress incontinence (short-term results)]. AB - We performed the transvaginal approach described by S. Raz for stress urinary incontinence and cystocele. 13 patients with cystocele and stress urinary incontinence underwent the four corner Bladder neck suspension 12 patients with stress urinary incontinence alone underwent simple bladder neck suspension. After a median follow-up of 4,1 months 92% were cured of incontinence. Cystoceles grade II and III were completely reduced. These results are comparable with abdominal approach for less morbidity and shorter hospital stay. PMID- 1414736 TI - HIV infection and rape. AB - We report the case of a woman who was found to be HIV positive after a sexual assault, in the absence of other risk factors for HIV infection. This observation and the report of one similar case support the view that HIV may be transmitted to a victim of a single sexual assault. We believe that all victims of rape should be offered a test for HIV and offered counselling. In addition to the current recommendations, the semen obtained should be tested for HIV antibodies by Western blot analysis. In the absence of clear data on safety and efficacy, we should recommend neither routine application of virucidal agents nor systematic Zidovudine (AZT) prophylaxis. PMID- 1414737 TI - [Oral purine loading test for latent metabolic disorders of uric acid in patients with calcium containing upper urinary calculi]. AB - For the detection of metabolic disorders of uric acid in upper urolithiasis, an oral purine loading test was performed in 78 patients with calcium-containing calculi, 5 patients with uric acid calculi, and 34 stone free subjects. From the results of the normal subject group, the criteria of hyperuricemia, latent hyperuricemia, hyperuricosuria and latent hyperuricosuria were proposed. In calcium-containing stone formers, 6 male patients showed hyperuricosuria, 18 male patients and 4 female patients showed latent hyperuricemia or latent hyperuricosuria. In uric acid urinary stone formers, all cases showed latent hyperuricemia or latent hyperuricosuria. These findings indicated that the metabolic disorders of uric acid might be one of the risk factors for the formation of calcium containing urinary stones, as well as uric acid urinary stones. PMID- 1414738 TI - [Evaluation of kidney graft function with dynamic MRI--preliminary report]. AB - The value of dynamic magnetic resonance imaging (MRI) in the examination of the function of transplanted kidneys was examined. Dynamic MRI was performed on 14 renal transplant patients. After the injection of Gd-DTPA (dimeglumine gadopentetate), we used small tip angle gradient echo (STAGE) technique with a flip angle of 20 degrees. The cortex was higher in signal intensity of well functioning grafts than the medulla before the injection in Gd-DTPA. Signal intensity of the cortex decreased after 30 seconds. After 1 minute the signal intensity of the cortex recovered and low intensity band meaning passage of Gd DTPA at corticomedullary differentiation was displayed. Signal intensity of the medulla decreased after 3 minutes. Signal intensity of the parenchyma of transplanted kidney after 5 minutes was much the same as that before injection. Image of poor functioning grafts displayed unclear figures. Time-intensity values of both cortex and medulla in well functioning grafts decreased rapidly after about 2 minutes, and rose thereafter. Time-intensity curves of both cortex and medulla were almost flat on and after 5 minutes. Time-intensity curves of both cortex and medulla in poor functioning grafts were almost flat through out the examination. We concluded that effective parameters of the graft function for the time-intensity curve were delta I1 and delta I2. Dynamic MRI was suggested to be useful in the evaluation of kidney graft function. PMID- 1414739 TI - [Treatment of endocrine-resistant stage D carcinoma of the prostate with a cisplatin derivative (DWA2114R): a pilot study]. AB - DWA2114R (DWA) is a new derivative of platin compounds. Eleven patients with rapidly progressive, endocrine-resistant stage D carcinoma of the prostate were treated with infusion of DWA (800-1,000 mg/m2) every 3 to 4 weeks. A partial objective response was observed in 3 of 11 patients (27%). This response lasted from 5 to 11 months with an average of 7.7 months. Six patients (55%) had a significant decrease or disappearance of bone pain and five became ambulatory and asymptomatic. Four patients (36%) showed no change, and four patients (36%) did not respond to the treatment and showed progression of their disease. There were no patients with severe leukopenia (less than 1,000/mm3). No significant renal toxicity was observed in any of the patients and gastrointestinal toxicity was tolerable. DWA appears to be an effective drug available for the treatment of endocrine-resistant advanced carcinoma of the prostate. PMID- 1414740 TI - [Clinical study of the epidermal growth factor contents in urine, plasma and tissue from the patients with urological diseases]. AB - Contents of epidermal growth factor (EGF) in urine, plasma and tissues in urological diseases were estimated by enzyme immunoassay using beads bound to the anti-EGF antibody, and the clinical significance of the presence of EGF in the disease state was examined. There was no difference in EGF level between healthy male and female subjects (n = 22), and the level showed a tendency to decrease with age (p less than 0.05). The subjects were 19 cases of prostatic cancer, 7 of renal cancer, and 12 of urinary bladder cancer. The difference in EGF level between the healthy subjects and patients was not significant, and the levels were shown to be lower in 8 cases of renal insufficiency (including patients on hemodialysis:HD)(p less than 0.01). Plasma EGF levels in the 30 healthy subjects revealed no significant differences related to sex or age. Plasma EGF levels were lower in 42 cases of renal insufficiency (before and after HD), and in 7 cases of renal cancer (p less than 0.01); they ware significantly lower in 15 cases of prostatic cancer (p less than 0.05). In tissues including tumor sites, EGF levels were higher particularly in the prostatic gland tissue (hypertrophy and cancer regions). Thus, urinary and plasma EGF levels in urological diseases may be useful parameters of renal function, but its relationship with malignant diseases is still unknown. The EGF level should be explored in relation with the EGF receptor. PMID- 1414741 TI - [A case of retroperitoneal teratoma showing high level of CA19-9]. AB - We report a case retroperitoneal mature teratoma showing an abnormally high CA19 9 (carbohydrate antigen 19-9) serum level in a 30-year-old woman. She was hospitalized for an episode of left upper abdominal pain. High CA19-9 tissue level and immunohistochemical findings were found in removed tissue. This case is the third report of a CA19-9-producing teratoma and literature was reviewed and discussed. PMID- 1414742 TI - [Bilateral adrenal metastasis from renal cell carcinoma]. AB - A case of renal cell carcinoma with synchronous bilateral adrenal metastasis occurring in a 76-year-old woman is reported. In our case, preoperative computed tomographic evaluation revealed the presence of bilateral adrenal metastasis, and simultaneous right radical nephrectomy and contralateral adrenalectomy were performed. Pathological examination revealed renal cell carcinoma of right kidney metastasizing to both adrenal glands. Bilateral adrenal metastasis from renal cell carcinoma is rare. Our case seems to be the fourth case in the Japanese literature. PMID- 1414743 TI - [Renal cell carcinoma with malignant peritoneal mesothelioma: report of a case]. AB - We report a case of left renal cell carcinoma extending into vena cava with malignant peritoneal mesothelioma. A 41-year-old man presented to our outpatient clinic with macroscopic hematuria. Upon laparotomy, numerous white nodules were identified on diaphragm and serosa of liver, stomach, small intestine and mesentery. Biopsied specimen showed malignant mesothelioma of peritoneum and renal cell carcinoma of left kidney. He was treated with intraperitoneal cisplatinum and intravenous pirarubicin for mesothelioma, and chemoembolization for renal tumor. After two courses of therapy, he suffered from disseminated intravascular coagulation and died of subarachnoid hemorrhage. Autopsy revealed that intraperitoneal nodules were markedly decreased in number and renal tumor had changed into hemorrhagic necrosis, but tumor thrombus in vena cava had little necrotic change. PMID- 1414744 TI - [Transitional cell carcinoma of the ureter with inverted proliferation: a case report]. AB - A case of transitional cell carcinoma of the ureter with inverted proliferation is presented. A 74-year-old man with the chief complaint of asymptomatic macrohematuria was referred for a suspicion of a ureteral tumor. Excretory urography demonstrated a filling defect with a round smooth contour in the right lower ureter. Urine cytology was negative for malignant cells. No bladder tumor was noted by cystoscopic examination. Under the clinical diagnosis of a right ureteral tumor, right total nephroureterectomy was performed. The gross specimen contained a 2.0 x 1.0 cm, polypoid, pedunculated and smooth-surfaced tumor. The pathological diagnosis was transitional cell carcinoma with inverted proliferation G2 much greater than G1. Malignant tumor with inverted proliferation in the ureter is very rare. In Japan, 8 cases of transitional cell carcinoma with inverted proliferation in the ureter, including our case, are reviewed. PMID- 1414745 TI - [Ectopic ureter opening to vestibule without urinary incontinence: a case report]. AB - A case of a 2-year-old female with right ectopic ureter opening in vestibule vaginae and without urinary incontinence is reported. Excretory urogram showed mild dilatation of the upper right segment with bilateral complete duplication. Right ectopic ureter some functioning upper segment of the kidney was reimplanted into the bladder to avoid surgical intervention for heminephrectomy. According to the retrograde ureterogram of ectopic ureter the running courses and shapes of the dilated distal portions of ureters were compared between two groups, ectopic ureter with incontinence and that without incontinence. We suppose the continence mechanism of ectopic ureter is kept when the running course of the ureter through some portion of the urethral sphincter musculature. PMID- 1414746 TI - [Male bladder leiomyoma: a case report]. AB - A case of leiomyoma of the urinary bladder in a 40-year-old man is reported. Enucleation of the tumor was performed, because transurethral resection-biopsy revealed a bladder leiomyoma. Ninety nine cases of a bladder leiomyoma have been reported in Japan, but male cases are rare. PMID- 1414747 TI - [Posterior urethral polyp: a recurrent case]. AB - A 38-year-old man was admitted to our hospital complaining of difficult, frequent urination to our hospital. Transrectal echography and digital examination showed chronic prostatitis. He was treated with medication for chronic prostatitis but his condition did not improve. Retrograde urethrography revealed an obstructive change in the prostatic urethra and urethroscopic findings showed a urethral tumor in the posterior urethra. Transurethral resection of the tumor was performed. Pathological diagnosis of the urethral tumor indicated a urethral caruncle. After one year, the patient was readmitted to our hospital with the same complaints as before. Urethroscopic findings revealed the recurrence of a urethral polyp in the posterior urethra. Transurethral resection of the polyp was performed. Pathological findings revealed that the inner structure of the polyp showed a prostatic glandular pattern that after staining with anti-prostatic acid phosphatase antibody. The final diagnosis was that the polyp had a prostatic-type epithelium in the prostatic urethra. PMID- 1414748 TI - [Clinical study of terodiline hydrochloride for the treatment of urinary frequency and urinary incontinence, and its cardiovascular adverse effects]. AB - We evaluated the effectiveness and side effects of terodiline hydrochloride in 109 patients with urinary frequency and urinary incontinence. The drug was administered at a dose of 24 mg once a day or 12 mg twice a day for 4 weeks. Symptoms such as urinary frequency and urinary incontinence were alleviated in 101 out of 109 patients (92.7%). Mild side effects such as thirst, dysuria, sense of residual urine, orthostatic hypotension and arrhythmia were observed in 9 out of 109 patients (8.2%). Side effects such as orthostatic hypotension and arrhythmia were observed on the 28th day or the 20th day of the administration, but these symptoms disappeared with discontinued use of this medicine. The results obtained from this study suggest that terodiline hydrochloride may be greatly useful for the patients with urinary frequency and urinary incontinence. But we must take account of the side effects such as orthostatic hypotension and arrhythmia. PMID- 1414750 TI - [The relationship between pathological spreading factors and tumor size in 45 patients with renal cell carcinoma]. AB - The relationship between pathological spreading factors (T3,4 V+, N+, M+) and tumor size was studied in 45 patients with renal cell carcinoma during the past 10 years from 1982. The incidence of having one or more factors was 0% for the 17 tumors smaller than 5 cm, but 75% for the 28 tumors over 5 cm. The mean diameter of the tumors having a T, V, N or M factor was significantly larger than that of tumors having no factor (T1,2V0N0M0). These findings suggest that they have a higher tendency of having spreading factors once the tumors have exceeded a certain size. PMID- 1414749 TI - [The phase IV studies with Estracyt in prostatic cancer--supplementary report: results of long-term therapy]. AB - Two hundred patients with prostatic cancer were enrolled in our previous study between 1984 and 1987. In this study, 96 patients of them were observed for 1 year or more after oral administration of Estracyt (estramustine sodium phosphate). Of these 96 cases, 33 patients were treated with Estracyt as primary treatment and 63 patient had been treated with other treatments before Estracyt treatment. Twelve patients were treated only with Estracyt and 84 patients also received other treatments. Thirty-eight patients were on primary therapy, 37 patients were on maintenance therapy, and 11 patients were on primary therapy, 37 patients were on maintenance therapy, and 11 patients were on the re-activated stage therapy and 10 patients were others. In conclusion, among the 67 cases in which the due judgement of the effect was possible, Estracyt was markedly effective in 10 cases (14.9%), effective in 16 cases (23.9%), slightly effective in 15 cases (22.4%) and ineffective in 26 cases (38.8%). The survival rate was 92.6% at the first year, 66.0% at the third year and 46.3% at the fifth year in the follow-up study. Adverse reactions were observed in 22 cases (22.9%), among which the administration was discontinued in 3 cases. PMID- 1414752 TI - [Transitional cell carcinoma of the upper urinary tract following total cystectomy for bladder cancer]. AB - From 1975 to 1990, we treated 118 patients with urinary epithelial cancer, including 100 with primary bladder cancer, 13 with primary upper urinary tract cancer, and 5 with both diseases. Thirty-five patients with primary bladder cancer underwent total cystectomy. Upper urinary tract urothelial cancer developed in 4 patients (4.0%) and was detected only after cystectomy. Three patients had multiple bladder tumors before cystectomy and recurrent tumors under long-term bladder-preserving treatment. The other patient had had cystectomy for the primary bladder lesion. Our present policy is to perform urinary cytology once a month and intravenous urography once a year in patients with bladder cancer for early detection of secondary upper urinary tract cancer. PMID- 1414751 TI - [A clinical investigation on renal pelvic and ureteral tumors]. AB - Sixty-six patients with renal pelvic and ureteral tumors were treated in our hospital between June 1974 and June 1991. These cases consisted of 27 renal pelvic tumors, 31 ureteral tumors and 8 renal pelvic and ureteral tumors. Their ages ranged from 43 to 86 years old (average: 65). There were 46 males and 20 females. The surgical method involved total nephroureterectomy with a cuff for 44 patients, nephroureterectomy for 3, nephrectomy for 9, total nephroureterectomy with total cystectomy for 5 and partial ureterectomy for 2. Histologically, there were 60 transitional cell carcinomas (TCC), 2 squamous cell carcinomas (SCC) and 4 TCC with SCC. As for the pathological stage, 13 were pTa, 16 pT1, 12 pT2, 11 pT3, 13 pT4 and 1 pTX. Subsequent bladder tumors were found in 13 patients (19.7%). The overall survival rate at 1, 3 and 5 years were 80%, 68% and 52%, respectively according to the Kaplan-Meier's method. In this series, the pathological staging was the most important prognostic factor. PMID- 1414753 TI - [Application of video endoscope system (EVIS200) in endourology]. AB - We began clinical studies in April, 1989 for the purpose of utilizing the video endoscope system in the field of urology, termed the Urological Video Information System (UVIS). The UVIS is made up of an image assembling and recording system and an image filling system. Since we started using the first generation video endoscope system (EVIS-1, Olympus Optical Co.) as an image assembling system, we have encountered several major obstacles such as 1) the absolute insufficiency for the amount of light, and 2) the unclearness of frozen images. As we have been able to use as second generation video endoscope system (EVIS200, Olympus Optical Co.) since September 1990, the major components of the UVIS have been modified. In this report, we describe our clinical experience with the re-designed UVIS; EVIS200, which we have used, is composed of a video-processor (CL-200, Olympus Co.), a video converter and rigid urological scopes. The EVIS200 has been evaluated not only for the endoscopic examination but also for transurethral surgery. No problems were noticed in manipulating the EVIS200. Marked improvements were achieved in image quality. Images both on the television monitor and hard copies from the color video printer had optical quality in good agreement with the gross findings. The UVIS was a great contribution to both the authors and the patients; the findings both of the examination and the surgery could be explained to the patient and family during and/or immediately after the procedure. We believe that the UVIS may replace conventional urologic endoscopy and become an excellent date-base for endourology. PMID- 1414754 TI - [A case of a child with extra-adrenal pheochromocytoma associated with renovascular hypertension]. AB - A 7-year-old female was discovered to be severely hypertensive. Urinary noradrenaline excretion and plasma noradrenaline level were elevated. Plasma renin activity was markedly elevated. She was found to have a mass in the hilus of the left kidney and left renal artery stenosis. Magnetic resonance imaging (MRI) of the mass revealed an extremely bright lesion on T2 weighted image. DMSA renal scintigraphy revealed a low uptake rate (4.7%) in the left kidney. A diagnosis of extra-adrenal pheochromocytoma associated with left sided renal artery stenosis was made. The mass and left kidney were removed. Electronmicroscopic examination of the mass revealed characteristic neurosecretory granules. There was only slight fibrosis in the wall of the removed left renal artery. PMID- 1414755 TI - [A case of retroperitoneal venous aneurysm]. AB - A case of retroperitoneal venous aneurysm is reported. A 73-year-old woman was referred to us with the chief complaint of left abdominal mass. A giant abdominal mass was palpable and diagnostic imaging examination including ultrasound tomography, excretory pyelography, computed tomography, magnetic resonance imaging and angiography revealed a giant cystic mass encircled by calcification in the left retroperitoneal space. Operation for this cystic mass was performed under the preoperative diagnosis of a giant left renal cyst. During operation the mass was located between the left kidney and the left adrenal gland. Because it was difficult to separate the mass from the left kidney the mass was removed with the left kidney. The extirpated tumor measured 15.5 x 15.0 x 9.5 cm and contained old blood clots and red-yellow colored fluid. A histological examination revealed that the tumor wall was composed of smooth muscle and elastic fibers. Therefore, pathological diagnosis was retroperitoneal venous aneurysm. Retroperitoneal venous aneurysm is very rare. To our knowledge, this is the 8th case of retroperitoneal venous aneurysm reported in Japan. PMID- 1414756 TI - [A case of retroperitoneal Castleman's disease associated with bladder tumor and a review of 59 cases in Japan]. AB - We present a case of retroperitoneal Castleman's disease associated with bladder tumor. The patient was a 62-year-old man, who underwent partial cystectomy under a diagnosis of bladder tumor in 1989. Subsequently, recurrent bladder tumor was detected and he consulted the outpatient clinic at our University Hospital in November, 1990, at which time computerized tomography (CT) revealed a retroperitoneal tumor. From February, 1991 four courses of combined chemotherapy (methotrexate, vinblastine, pirarubicin, cisplatin) were administered for the tumor. The tumor reduction rate after the chemotherapy was 60% on CT, and retroperitoneal lymph node dissection and left nephroureterectomy were performed in July, 1991. Histological examination revealed Castleman's disease, hyaline vascular type. Fifty-nine reported cases of retroperitoneal Castleman's disease in Japan are reviewed. PMID- 1414757 TI - [A report of two cases of multilocular cystic renal cell carcinoma: review of 51 cases reported and the results of a prognostic survey]. AB - We report 2 cases of multilocular cystic renal cell carcinoma. One was in a 33 year-old male, presenting with ultrasonic abnormality of the left kidney at an annual employee health care examination. Computerized tomography (CT) demonstrated a 5 cm of multilocular cystic mass adjacent to the lower pole of the left kidney. Another was in a 44-year-old male, presenting with microscopic hematuria at an annual employee health care examination. CT of the abdomen revealed a 6.5 cm of multilocular cystic mass on the upper pole of the right kidney. Both were diagnosed as renal cell carcinoma by the angiography and underwent radical nephrectomy. Gross specimens showed typical multilocular cystic appearance and histopathology showed clear cell carcinoma infiltrating septa and replacing epithelium of the cyst walls. Both patients are alive without evidence of disease at, 21 months and 14 months after operation, respectively. Including our cases, 51 multilocular cystic renal cell carcinoma and multilocular cystic nephroma associated with renal cell carcinoma have been reported. From the review of the literatures and the answer of the questionnaires inquiring about the outcome of the patient to Japanese reporters, the outcome of 38 patients was ascertained. The 10-year survival rates and non-recurrence rate after operation calculated by the Kaphan-Meier formula were 97.3% and 90.3%, respectively. Because of the good prognosis of reported cases, we concluded that we should choose kidney-sparing surgery for the operation of multilocular cystic renal cell carcinoma. PMID- 1414758 TI - [Dilated cardiomyopathy following alpha interferon therapy of renal tumor with pulmonary metastases: a case report]. AB - We report a case of renal cell carcinoma with pulmonary metastases treated with recombinant alpha interferon and subsequently presenting as congestive heart failure due to a dilated cardiomyopathy. A 66-year-old man presented himself to the department of internal medicine at our hospital with a complaint of persistent cough with sputum on August 27, 1988. Ultrasonogram, computed tomography and angiography showed a right renal cell carcinoma and chest x-ray films disclosed bilateral multiple nodular shadows, probably representing metastases of the renal tumor. After being transferred to our department, the patient underwent the ligation of the right renal artery and vein and the postoperative treatment with recombinant alpha interferon, achieving a complete response for pulmonary metastases and a partial response for the primary region. On February 14, 1990 the patient was admitted to our hospital with a complaint of dyspnea to be diagnosed as congestive heart failure due to dilated cardiomyopathy. The interferon therapy was suspected to have caused the heart disease, and four months after discontinuation of interferon therapy the heart failure symptoms had improved, but hypokinesis of the cardiac wall still persisted. To our knowledge, this may be the first case of alpha interferon related cardiomyopathy in Japan. PMID- 1414759 TI - [A case of renal cell carcinoma in childhood]. AB - We report a case of renal cell carcinoma in a 6-year-old girl. The child had the chief complaints of gross hematuria and abdominal pain. An examination using ultrasound, computerized tomography scans and angiography showed a left renal tumor. Left side radical nephrectomy with lymphadenectomy was performed. Histopathological examination revealed renal cell carcinoma of clear cell type with metastasis to the hilar lymph node. She received postoperative therapy with interferon. Now, 3 years since the operation, she is living without evident recurrence. We reviewed 89 Japanese cases of renal cell carcinoma in children including this case and have discussed symptoms, differential diagnosis and treatments. PMID- 1414760 TI - [A case of renal squamous cell carcinoma associated with giant hydronephrosis and ureteral stone: efficacy of imaging modality]. AB - A rare case of squamous cell carcinoma of the right kidney associated with giant hydronephrosis and right ureteral stone was reported. A 60-year-old woman was referred to our department with a complaint of ileocecal dull pain. A plain computerized tomogram (CT) revealed giant hydronephrosis, and a kidney-ureter bladder X-ray revealed a right lower ureteral stone. A right percutaneous nephrostomy was done and antegrade pyelography revealed giant hydronephrosis and a ureteral stone, but showed no intrapelvic filling defect. Under the diagnosis of right ureteral stone with hydronephrosis, right ureterolithotomy was done. However, since the inflammation did not subside after ureterolithotomy, right nephrectomy was done. The surgically removed right kidney did not show any evident tumor mass, a histological study revealed squamous cell carcinoma involving renal parenchyma. The patient received no adjuvant therapy and died 3 months after nephrectomy with sudden appearance of bone, liver and pulmonary metastases. The preoperative efficacy of imaging modalities for renal squamous cell carcinoma was discussed herein. PMID- 1414761 TI - [Multiorgan failure following intravesical bacillus Calmette-Guerin administration: a case report]. AB - We describe a case of multiorgan failure after intravesical bacillus Carmette Guern (BCG) immunotherapy for bladder cancer. A 58-year-old man with superficial transitional cell carcinoma of the bladder was initially treated by transurethral resection and intravenous chemotherapy, and then administered 11 sessions of BCG intravesically. He was administered BCG intravesically after cystoscopic examination. The next day he complained of nausea and malaise. He became hypotensive. The symptom progressed with multiorgan failure, disseminated intravascular coagulation and respiratory failure. The patient gradually improved with administration of antibiotics and corticosteroid, and hemodialysis, without antituberculous antibiotics. Intravesical instillation of BCG should not be carried out immediately after cystoscopic examination. PMID- 1414762 TI - [Pure leiomyoma of prostate presenting with rectal symptoms: a case report]. AB - Pure leiomyoma of the prostate is a rare lesion. We report a case in a 68-year old man who presented with rectal symptoms. Rectal examination showed a stony hard nodule with irregular surface near the apex of the prostate. Transrectal sonography showed a homogeneous well defined nodule measuring 3.5 cm in diameter in the left prostatic lobe protruding into the bladder. Magnetic resonance imaging (MRI) revealed an irregular shaped mass in the prostate with an isosignal to muscle in the T1 weighted images. Needle biopsy revealed pure leiomyoma histologically. Transurethral resection was performed and a nodule of white almost avascular tissue was resected in the apex proximal to vermontanum. After operation, the rectal symptoms improved. PMID- 1414763 TI - [Traumatic dislocation of the testis]. AB - Dislocation of the testis is a rare injury, with only 73 cases having been reported in Japan. We herein add 6 cases. Lately, accidents involving teenage patients, primarily involving motorcycles, have been increasing. Closed reduction is recommended, but it was successful only 5 of 73 cases. The results of testicular biopsies suggest that early surgical management is required when closed reduction is unsuccessful. PMID- 1414764 TI - [Clinical statistics on inpatients admitted to the Department of Urology, Hyogo Prefectural Hospital Nishinomiya during 20 years from 1972 to 1991]. AB - A statistic analysis was carried out on the 4,956 inpatients admitted to our Department of Urology from April 1972 to December 1991. The patients included 3,399 males and 1,557 females. A total of 4,105 operations including 255 renal allotransplantations were performed on 3,590 patients. Open surgery for upper urinary tract stones has been replaced by extracorporeal shock-wave lithotripsy (ESWL) in the last three years. PMID- 1414765 TI - [Experimental urinary tract infection caused by Escherichia coli in diabetic mouse--uroepithelial colonization and polymorphonuclear leukocyte function]. AB - Relationship between polymorphonuclear leukocyte (PMN) function and susceptibility to infections in diabetic mice was studied. In the experimental urinary tract infections, 6 strains of Escherichia coli with different fimbrial expression and hemolysin production were used. In contrast with non-fimbriated strains, fimbriated strains were more susceptible to phagocytosis by PMN. MS+.MR+ strains, however, showed resistance to intracellular killing by PMN. OEC-709, OEC 716 (MS+.MR+ strains), and OEC-734 (MS+.MR- strains), also showed resistance to the bactericidal activity of the serum. The killing activities of PMN derived from diabetic mice against these 3 strains were significantly lower than those of PMN from normal mice. In normal mice, MS+.MR+ strains showed the strongest colonization ability to the bladder and kidney, whereas MS-.MR- strains showed the weakest ability among the strains. In diabetic mice, the number of bacteria colonizing to the bladder and kidney was higher than that in normal mice, except for one MS-.MR- strain. Significant differences were observed in the strains (OEC 709, 716, 734), in which PMN was concerned strongly in the bacterial killing. Finally, these findings suggest that deterioration of the bactericidal activity of PMN in a diabetic state is involved in increased susceptibility of diabetic mice. PMID- 1414766 TI - [Influences of bacteria within stones on ESWL treatment]. AB - On 26 patients with upper urinary stones treated by extracorporeal shock wave lithotripsy (ESWL), the influences of the bacteria within the stones on the inflammatory complications, especially on urinary tract infection, after the ESWL treatment, were studied. The constituents of the stones obtained from these 26 patients consisted of the mixed stone of calcium oxalate and calcium phosphate (10 patients), calcium oxalate alone (2 patients), calcium phosphate alone (1 patient) and uric acid (1 patient). Of these 26 stones including no infection stones such as struvite and carbonate apatite, 5 stones (19.2%) had bacteria within the stone. Although no patients had severe inflammatory complications after ESWL treatments, the fact that the patient group having bacteria within the stones had a significantly elevated body temperature at one day after ESWL treatment compared to that on the preoperative day (P < 0.01) suggests that we should take into consideration the bacteria within non-infection stones as one of the risk factors of inflammatory complications after ESWL treatment. PMID- 1414768 TI - Transitional cell carcinoma of the renal pelvis associated with cyclophosphamide therapy. PMID- 1414767 TI - Retroperitoneal neurilemoma: CT and MR findings. AB - OBJECTIVE: Our objective was to characterize the CT and MR imaging findings of retroperitoneal neurilemomas. MATERIALS AND METHODS: We reviewed the CT and MR imaging findings in six women with retroperitoneal neurilemomas. RESULTS: Retroperitoneal neurilemomas were round, 5-13 cm in diameter, and located in the presacral pelvic retroperitoneum in four patients and adjacent to the kidney in two patients. CT findings of the tumors were well-demarcated round masses showing prominent cystic changes and oriented in a somewhat radial fashion. Medium and heavily T2-weighted MR images showed high-intensity necrotic areas and nonnecrotic areas of various signal intensity. CONCLUSION: CT findings of a round mass with prominent cystic degeneration, along with certain MR imaging characteristics, may be helpful in the preoperative diagnosis of retroperitoneal neurilemomas. PMID- 1414769 TI - Sonographic appearance of the torsion knot in spermatic cord torsion. PMID- 1414770 TI - MR imaging of the quadriceps tendon: normal layered configuration and its importance in cases of tendon rupture. AB - OBJECTIVE: The quadriceps tendon is a multilayered structure with separate layers arising from different muscle groups. We examined this layered configuration on MR images to determine if it is relevant in the evaluation of the traumatized quadriceps tendon. MATERIALS AND METHODS: Sagittal and axial T1-weighted MR images of 52 knees with normal tendons were reviewed to determine the number and the muscle origins of these layers. Five knees with traumatized quadriceps tendons were imaged with T1 and T2 weighting to determine the relationship between the layered configuration and the injury. RESULTS: All the normal quadriceps tendons had a laminated appearance with either four (6%), three (56%), or two (30%) layers. In 8%, the laminations were barely perceptible. The site of origin of each layer was consistent, and each favored a given muscle. The superficial layer originated from the posterior fascia of the rectus femoris muscle, and the deep layer originated from the anterior fascia of the midline vastus intermedius muscle. The middle layer(s) arose from the deep fascia separating the vastus medialis and the vastus lateralis muscles from the vastus intermedius muscle. When only two layers were present, the middle layer merged with the superficial and deep layers. In the injured tendon, complete rupture produced transection of all the layers. Incomplete ruptures were seen as focal discontinuities of individual layers; other layers remained intact. CONCLUSION: The existence of a layered configuration of the quadriceps tendon is significant in the MR examination of partial ruptures. It can help not only in detecting and localizing injuries but also in determining appropriate treatment based on the number or thickness of injured layers. PMID- 1414771 TI - Mucormycosis osteomyelitis causing avascular necrosis of the cuboid bone: MR imaging findings. PMID- 1414772 TI - Rapid growth of femoral herniation pit. PMID- 1414773 TI - Relapsing-remitting multiple sclerosis: sequential enhanced MR imaging vs clinical findings in determining disease activity. AB - OBJECTIVE: Sequential MR imaging frequently shows disease activity (clinically silent new brain lesions) in subgroups of patients with multiple sclerosis and therefore is valuable in monitoring the effects of treatment. Monitoring of disease activity in patients being treated for relapsing-remitting multiple sclerosis will increase in importance as new and safe therapies are developed. We studied sequential enhanced MR images of patients with early relapsing-remitting multiple sclerosis to define the MR features that indicate disease activity in this subgroup of patients and to compare MR imaging and clinical findings for this purpose. SUBJECTS AND METHODS: Seven patients with relapsing-remitting definite multiple sclerosis were examined monthly for 4-12 months. For each image, a standard repositioning protocol consisting of three images was used to ensure reproducibility of axial (double oblique) image planes, planned according to internal landmarks. A total of 58 unenhanced T2-weighted and enhanced T1 weighted MR images were obtained. RESULTS: MR images showed new enhancing lesions in six of the seven patients. On 25 (43%) of the 58 enhanced T1-weighted MR images, a total of 50 new enhancing lesions were observed, and on one image a reenhancing lesion was seen. The unenhanced T2-weighted images showed corresponding abnormalities for 92% of the new enhancing lesions. At follow-up, most lesions (86%) were enhanced on only one occasion: 4% were enhanced on more than two consecutive monthly MR examinations. Forty-nine percent of the lesions seen on T2-weighted images "disappeared" (beyond the resolution of the imaging system) after a mean follow-up of 3.5 months, especially lesions that were initially smaller than 5 mm. During the study, only five clinical relapses occurred in three patients (all at times when MR images showed contrast-enhancing lesions), and fixed disability did not increase. On 21 additional occasions, MR images showed new enhancing or reenhancing lesions in patients who were clinically stable at the time (4.2 times more clinically silent disease activity). CONCLUSION: Our results suggest that contrast-enhanced MR imaging is more sensitive than clinical monitoring for detecting new disease activity in patients with relapsing-remitting multiple sclerosis and that MR imaging might be useful in the evaluation of therapeutic regimens. PMID- 1414774 TI - Evaluation of complex cystic masses of the brain: value of steady-state free precession MR imaging. AB - OBJECTIVE: This study evaluated the effectiveness of steady-state free-precession (SSFP) MR imaging of complex cystic masses of the brain compared with that of conventional T1- and T2-weighted spin-echo imaging. Our hypothesis is that SSFP MR images provide better characterization of these masses and facilitate more appropriate preoperative diagnoses and planning. SUBJECT AND METHODS: Axial T1 weighted and SSFP MR images and specimens for pathologic examination were obtained in seven consecutive patients, 9-81 years old, with cystic mass lesions of the brain and neurologic symptoms and signs directly related to the masses. Axial contrast-enhanced T1-weighted images were obtained in six patients, surgical exploration was done in five patients, and stereotaxic biopsy was done in two. After examination of the routine spin-echo and SSFP images, the usefulness of SSFP images was determined by how well they facilitated correct preoperative diagnosis. RESULTS: On SSFP MR images, the solid or inhomogeneous components of a cystic mass had extremely low signals in contrast to the high signal of surrounding fluid. On routine spin-echo images, however, the signals of these components were masked by the signal of the surrounding fluid. SSFP MR images helped markedly in diagnosis of hemorrhagic, epidermoid, and arachnoid cysts. In cases of enhancing brain tumors, SSFP MR images provided the same information that contrast-enhanced images did. Overall, when SSFP MR imaging was used, more information about the texture and constituents of the cystic mass was obtained, and a more useful diagnosis was made. CONCLUSION: Initial results show that SSFP MR imaging is a more useful technique than conventional spin-echo imaging for characterizing complex cystic masses of the brain. SSFP MR imaging (1) allows distinction of edema from tumor, (2) helps establish where biopsy has the best chance of providing tissue that will show pathologic changes, and (3) helps distinguish simple cysts from tumors, tumor-cyst, or multicompartmental cyst and may be particularly helpful in detecting the contents of hemorrhagic cysts. PMID- 1414775 TI - The value of cerebral angiography in predicting cerebral ischemia during carotid endarterectomy. AB - OBJECTIVE: Temporary occlusion of the carotid artery during endarterectomy can result in ipsilateral cerebral ischemia if collateral blood flow is insufficient. This requires placement of a shunt across the carotid bifurcation, which is associated with increased operative risk. We retrospectively analyzed preoperative cerebral angiograms and intraoperative electroencephalographic recordings to determine if ischemia during carotid endarterectomy could be predicted from angiographic data. MATERIALS AND METHODS: The cerebral angiograms of 30 patients were examined. Collateral blood flow to the hemisphere on the side of surgery was determined to be present if both proximal segments of the anterior cerebral artery and the anterior communicating artery were visualized, or if filling and washout of the ipsilateral posterior cerebral artery could be seen. Collateral flow was determined to be inadequate if the anterior collateral system was incomplete, and if either the ipsilateral posterior communicating artery was absent or the posterior cerebral artery filled without washout. This information was compared with intraoperative electroencephalographic and shunting data. RESULTS: Of 15 patients who had demonstrable collateral blood flow, 14 had stable electroencephalograms and did not require a shunt during surgery. In all 15 patients in whom no collateral flow to the ipsilateral hemisphere could be shown, electroencephalographic changes prompted placement of an intraluminal shunt. CONCLUSION: We found that the angiographic determination of inadequate collateral cerebral circulation correlated strongly with the development of intraoperative ischemia. This implies that routine preoperative cerebral angiograms can be used to alert the surgeon to the potential need for shunt placement during carotid endarterectomy. PMID- 1414776 TI - MR imaging and HMPAO scintigraphy in conjunction with balloon test occlusion: value in predicting sequelae after permanent carotid occlusion. AB - OBJECTIVE: Permanent occlusion of the internal carotid artery may be required for en bloc resection of a neck tumor or to treat certain aneurysms. The risk of ischemic infarct is usually assessed with carotid balloon test occlusion and concurrent distal arterial pressure measurement. However, up to 20% of patients who tolerate the test occlusion have delayed neurologic sequelae. We propose enhanced MR imaging and hexamethylpropyleneamine oxime (HMPAO) scintigraphy to detect subclinical signs of ischemia and hypoperfusion as adjuncts to the balloon test occlusion to identify patients at risk for delayed sequelae. SUBJECTS AND METHODS: We prospectively examined 12 patients referred for balloon test occlusion of the carotid artery. Serial measurements of distal occluded internal carotid pressure were recorded. 99mTc-HMPAO was injected IV after 2 min of asymptomatic test occlusion, and single-photon emission computed tomographic (SPECT) data acquisition was done 1-6 hr later. Contrast-enhanced MR imaging was performed 1-8 hr after completion of the 30-min test occlusion. Signs of decreased perfusion or ischemia on these tests were compared with the mean distal arterial pressure and neurologic status of the patient during test occlusion. RESULTS: Seven (58%) of 12 patients had abnormal findings on HMPAO scintigraphy or contrast-enhanced MR imaging. Only one patient had neurologic deficits that corresponded to abnormal MR enhancement. The other 11 patients (92%) remained asymptomatic during the 30-min test occlusion. Of these 11 asymptomatic patients, five (45%) had areas of decreased perfusion on scintigraphy and three (27%) had abnormal MR contrast enhancement suggesting residual focal ischemia as a result of the test occlusion. Mean arterial pressures in the distal occluded artery did not correlate well with the imaging results. CONCLUSION: HMPAO scintigraphy can show clinically silent areas of decreased perfusion, while enhanced MR shows signs of acute ischemia (i.e., significant hypoperfusion) associated with asymptomatic balloon test occlusion. Theoretically, such patients would be at increased risk for permanent sequelae after permanent carotid occlusion. PMID- 1414777 TI - MR imaging of clival and paraclival lesions. AB - A wide spectrum of diseases involve the clivus and paraclival structures. Primary neoplasms, metastatic tumors, and inflammatory, vascular, and hematopoietic disorders are the most common abnormalities to arise from or directly involve the clivus. MR imaging exquisitely shows and helps characterize the diseases that affect this area. Sagittal and coronal MR imaging allows precise localization and evaluation of the signal characteristics of a mass, enabling a more specific diagnosis. The multiplanar capabilities of MR imaging provide superb visualization of the adjacent cranial nerves and vascular structures, aiding in surgical planning and radiation therapy. In this pictorial essay, the MR imaging, CT, and conventional radiographic findings of various clival and paraclival lesions are illustrated. PMID- 1414778 TI - Miliary tuberculosis involving the brain: MR findings. PMID- 1414779 TI - Femoral artery pseudoaneurysms: value of color Doppler sonography in predicting which ones will thrombose without treatment. AB - OBJECTIVE: The purpose of this study was to evaluate the Doppler imaging characteristics of femoral artery pseudoaneurysms occurring after cardiac catheterization to determine if color Doppler sonography can be used to predict which pseudoaneurysms would ultimately thrombose spontaneously. MATERIALS AND METHODS: Over a 30-month-period, 24 pseudoaneurysms were studied with serial color Doppler sonography. The color flow, B-mode, and Doppler spectral images and clinical records of patients whose pseudoaneurysms demonstrated spontaneous thrombosis were compared with those of patients who required surgical repair of the pseudoaneurysm. RESULTS: We found no statistically significant differences between the patients whose pseudoaneurysms demonstrated spontaneous thrombosis and those treated surgically in regard to clinical parameters or the volume of the pseudoaneurysm, percentage of flow within the pseudoaneurysm, ratio of forward to reversed flow velocity in the pseudoaneurysm neck, duration of diastolic flow in the pseudoaneurysm neck, or length of pseudoaneurysm neck. However, on color Doppler images, the volume of flow in the lumens of pseudoaneurysms that thrombosed spontaneously (1.8 +/- 3.3 ml) was significantly smaller than the volume of flow in the lumens of those treated surgically (4.4 +/ 3.2, ml, p = .02). CONCLUSION: We conclude that pseudoaneurysms with small volumes of flow in the lumen are more likely to thrombose than are those with large volumes of flow in the lumen. However, color Doppler sonographic characteristics cannot be used to predict subsequent thrombosis. PMID- 1414780 TI - Closure of the ductus venosus in neonates: findings on real-time gray-scale, color-flow Doppler, and duplex Doppler sonography. AB - OBJECTIVE: Our objective was to document the anatomy, flow pattern, and time of closure of the ductus venosus in healthy full-term neonates. SUBJECTS AND METHODS: We examined the ductus venosus in 73 neonates by using gray-scale sonography, color flow imaging, and duplex Doppler sonography. Each neonate was examined 1-2 days after birth, 6-7 days after birth, and then every 3-4 days until closure was confirmed or the neonate was 18 days old. The length, width, and color flow and duplex Doppler characteristics of the ductus were noted. Closure of the ductus at 6-7 days after birth was examined with respect to birth weight, hemoglobin level, and gestational age. RESULTS: The ductus venosus, extending from the left portal vein to the inferior vena cava, was identified with all three techniques. The ductus was patent in all 73 neonates 1-2 days after birth. It was still patent in 41 (68%) of 60 neonates reexamined 6-7 days after birth and in two of three neonates (11% [7/60]) reexamined 17-18 days after birth. Blood flow within the ductus was cephalic, in a constant venous waveform. Initial flow velocity ranged from 0.15 to 0.70 m/sec and decreased consistently in subsequent examinations. There was no significant difference in birth weight, hemoglobin level, or gestational age between the group whose ductus was closed and the group whose ductus was open at 6-7 days after birth. CONCLUSION: The ductus venosus in neonates is consistently detectable on sonography. It is patent in a greater percentage of neonates, and for a longer time, than was previously shown with conventional radiographic studies with angiography. PMID- 1414781 TI - Giant fistula between the right coronary artery and the left ventricle: diagnostic significance of right posterior oblique chest radiograph. AB - Congenital coronary artery fistulas are uncommon. The prevalence of coronary artery fistulas in adults has been estimated as 0.13% [1]. Most of these fistulas communicate with the right atrium or ventricle or with the pulmonary artery; those emptying into the left atrium or ventricle are quite rare [2, 3]. Usually, patients with coronary artery fistula do not have clinical symptoms, and their chest radiographs do not show the corresponding shadow because the fistula is hemodynamically insignificant. When the fistula is large, however, chest radiographs show the secondary hemodynamic changes, such as cardiac enlargement or increased pulmonary vasculature, depending on the emptying site. Moreover, the silhouette of the dilated tortuous vessel itself can be seen on the chest radiograph. We have examined four patients, each of whom had a giant fistula in the right coronary artery emptying into the left ventricle, proved by coronary angiography. In this essay, we illustrate the chest radiographs of these patients and describe the radiologic features that permit a specific diagnosis or suggest a coronary artery fistula. PMID- 1414782 TI - Needle-tip localization during CT-guided abdominal biopsy: comparison of conventional and spiral CT. AB - OBJECTIVE: This study was performed to determine whether the time required for needle-tip localization during biopsy of the abdomen would be reduced if continuous-volume data acquisition, also known as spiral CT, were used for guidance instead of conventional CT. SUBJECTS AND METHODS: Forty patients had biopsies of an abdominal mass; half underwent needle-tip localizations with conventional CT and half with spiral CT. The times required to localize the needle for 104 needle passes were calculated; scanning and reconstruction times were included, and the radiologist's technique and procedural difficulties were deliberately excluded. The mean needle localization times with conventional and spiral CT were compared for the upper abdominal and pelvic regions by using the two-tailed unpaired Student's t-test. RESULTS: The mean time (+/- SE) for spiral CT was 35 +/- 2 sec compared with 105 +/- 18 sec for conventional CT (p < .001). When analyzed by region, times with spiral CT were shorter in both the upper abdomen (means, 37 sec for spiral CT vs 150 sec for conventional CT, p < .001) and pelvis (means, 25 sec for spiral CT vs 74 sec for conventional CT, p = .038); the magnitude of the improvement was greater in the upper abdomen. CONCLUSION: The time required to find the needle tip during guided biopsy of an abdominal mass is reduced with spiral CT compared with conventional CT. This improvement is partly a result of the ability to eliminate respiratory misregistration with spiral CT, which is not possible with conventional multisectional CT; hence the greater advantage in upper abdominal biopsy. PMID- 1414783 TI - Iodide mumps due to low-osmolality contrast material. PMID- 1414784 TI - Digital archive center: implementation for a radiology department. AB - OBJECTIVE: In this article, we describe the implementation of a digital archive center for a radiology department in a 700-bed teaching hospital. MATERIALS AND METHODS: The archive center consists of two identical archive systems, each comprising five components: an archive server, a data-base server, an optical disk library, a stand-alone optical disk drive, and a communication network. An image management system controls the image traffic from acquisition devices to display stations. A fault-tolerant mechanism was built into the archive center to achieve a 100% uptime. RESULTS: The center has been in operation for over 6 months. We have not experienced a single total system failure during this period. It currently archives all digital images from three MR units and four CT scanners and selected images from three computed radiographic systems and two laser film digitizers. The center archives between 1.5 and 2.0 gigabytes of images per workday. CONCLUSION: With its built-in fault-tolerant mechanism, we believe that the implemented archive center is very reliable and is suitable for a radiology department to archive its digital images. PMID- 1414785 TI - Capital planning in radiology. PMID- 1414786 TI - Subspecialization and certification in radiology. PMID- 1414787 TI - Handgun control: a public health issue. PMID- 1414788 TI - A system for full-motion real-time telesonography. PMID- 1414789 TI - An unusual cause of hemoptysis in an i.v. drug abuser. PMID- 1414790 TI - Glass foreign body in the breast simulating a hyperdense nodule on mammography. PMID- 1414791 TI - Unfavorable outcome of recent breast cancer screening trials: why? PMID- 1414792 TI - "Ductogram" associated with extravasation of silicone from a breast implant. PMID- 1414793 TI - Jejunogastric intussusception: diagnosis based on sonographic findings. PMID- 1414794 TI - Persistent pseudotumor of the bowel on sonography caused by stool in the colon. PMID- 1414795 TI - Osteoclast-type giant-cell tumor of the pancreas. PMID- 1414796 TI - Tiny echogenic foci in the liver. PMID- 1414797 TI - Testicular microlithiasis. PMID- 1414798 TI - Abdominal aortic aneurysm. PMID- 1414799 TI - Primary neuroblastoma of a vertebra: an unusual location for a variant of primitive neuroectodermal tumor of bone. PMID- 1414800 TI - Recurrent adult-type pharyngeal rhabdomyoma: MR appearance. PMID- 1414801 TI - Evaluation of congenital heart disease with MR imaging: current and coming attractions. AB - Nearly 10 years of experience in the use of MR imaging for the diagnosis of congenital heart disease has accumulated. Although MR imaging is superior to other techniques in showing certain structures and abnormalities such as small central pulmonary arteries in tetralogy of Fallot, aortic coarctations, and venous connections in heterotaxia syndromes, it remains an ancillary tool to echocardiography and cardiac catheterization. In this review, we examine present limitations and advantages of conventional MR in the evaluation of congenital anomalies of the heart and great vessels and explore future developments that might bring MR imaging into the diagnostic mainstream. Key improvements now in development are ultrafast MR systems for acquisition of multiple real-time MR images (in 30 msec or less) and on-line three-dimensional computer reconstruction of the heart and great vessels. Improved display and understanding of complex anatomy, as well as more extensive functional analysis of hearts before and after surgery, should be the benefits of such developments. PMID- 1414802 TI - Dr. DeWees. PMID- 1414803 TI - CT of the extraperitoneal space: normal anatomy and fluid collections. AB - Knowledge of the appearance and location of the normal fascial structures surrounding the kidneys and the bladder is the key to proper CT analysis of extraperitoneal fluid collections. Recent studies have shown that the renal fascia and the perirenal space are more complex than previously recognized. An extracapsular renal hematoma, confined against the kidney by the posterior renorenal septum within the perirenal space, can entirely simulate a subcapsular hematoma. Pancreatitis fluid can dissect between the discrete layers that constitute the posterior renal fascia, allowing fluid in the anterior pararenal space to extend posterior to the kidney without directly involving the posterior pararenal space. The umbilicovesical fascia separates the small perivesical space from the potential large reservoir of the prevesical space in the extraperitoneal portion of the pelvis. Fluid in the prevesical space can communicate directly with the retroperitoneal spaces surrounding the kidney. In addition to compartmental localization, CT features of the fluid itself or the presence of ancillary findings such as aortic aneurysm, enlarged pancreas, renal mass, or hydronephrosis will frequently indicate the cause and the extent of most extraperitoneal fluid collections. PMID- 1414804 TI - Color Doppler imaging of the hepatic vasculature. AB - Duplex sonography added a new dimension to real-time sonographic imaging and can be used to characterize flow dynamics. Unfortunately, duplex sonography also has significant drawbacks, most of which are the result of the limited sampling ability of pulse-gated technology and the inability to provide a global display of Doppler information. Sonographic imaging of intraabdominal vessels has improved markedly with the advent of color Doppler techniques. This article reviews the use of color Doppler sonography in the evaluation of hepatic vessels. The complementary role of Doppler spectral analysis is also considered. PMID- 1414805 TI - MR imaging of the lungs: value of short TE spin-echo pulse sequences. AB - OBJECTIVE: An experimental short echo delay (TE = 7 msec) T1-weighted spin-echo sequence was compared with a conventional (TE = 20 msec) T1-weighted spin-echo sequence in the assessment of normal and abnormal lung parenchyma. Comparison was also made with high-resolution CT of abnormal lung parenchyma. SUBJECTS AND METHOD: At 1.5 T, an experimental short echo delay T1-weighted multislice spin echo sequence (TR = RR interval, TE = 7 msec) was compared with an optimal conventional T1-weighted spin-echo sequence (TR = RR interval, TE = 20 msec, spatial presaturation). Ten healthy volunteers were examined with both sequences. The mean signal intensity and signal-to-noise ratios were calculated in lung parenchyma for both sequences. Two radiologists compared the visualization of normal lung parenchymal structures with the two techniques. In 24 patients with diffuse lung disease, results with both MR sequences and with high-resolution CT were compared. RESULTS: The signal intensity was significantly greater (p < .001) with the TE of 7 msec than with the TE of 20 msec, resulting in a 3.5-fold improvement in the signal-to-noise ratio. The 7-msec TE improved visualization of lung parenchymal structures, including peripheral vessels, interlobular septa or veins, and centrilobular arteries. In the patients with diffuse lung disease, pulmonary parenchymal abnormalities were better visualized on the images with TEs of 7 msec than on images with TEs of 20 msec. When compared with high-resolution CT, the sequence with a TE of 7 msec provided comparable assessment of air-space opacification and dense consolidation, but it was inferior to high-resolution CT in the anatomic assessment of lung parenchyma. CONCLUSION: This experimental spin echo sequence with a TE of 7 msec significantly improves the signal-to-noise ratio, allowing improved visualization of normal and abnormal pulmonary parenchyma when compared with conventional spin-echo images with a TE of 20 msec. Although anatomic detail remains inferior to that seen with high-resolution CT, the improved image quality with a TE of 7 msec suggests that assessment and follow-up of parenchymal lung disease might be possible with MR, thereby avoiding ionizing radiation. PMID- 1414806 TI - Chronic hypersensitivity pneumonitis: use of CT in diagnosis. AB - OBJECTIVE: In its subacute or chronic form, hypersensitivity pneumonitis is often difficult to distinguish clinically and physiologically from other idiopathic diffuse lung diseases. The aim of this study was to identify high-resolution CT features that allow distinction of chronic hypersensitivity pneumonitis from other chronic diffuse parenchymal lung diseases. MATERIALS AND METHODS: Six patients with chronic hypersensitivity pneumonitis were examined with pulmonary function testing, bronchoalveolar lavage, lung biopsy, chest radiography, and high-resolution CT. The chest radiographs and high-resolution CT scans were reviewed independently by three observers without knowledge of the patients' clinical status. Discrepancies between the observers were resolved by consensus. RESULTS: The chest radiographs revealed normal lung volumes with a combination of abnormalities: a mixed alveolar/interstitial pattern in five cases, peribronchiolar thickening in three, a diffuse granular pattern in one, and a linear fibrotic pattern in one. In general, the high-resolution CT scans showed more abnormalities than were apparent on the plain chest radiographs. High resolution CT revealed centrilobular, peribronchiolar, indistinct nodular opacities, of various numbers, in all cases. Four cases had areas of ground-glass density, three cases had lobular areas of hyperlucency, and one case had areas of pulmonary fibrosis and honeycombing. CONCLUSION: We confirm that high-resolution CT can most clearly show the type and distribution of parenchymal abnormalities in patients with hypersensitivity pneumonitis. Importantly, although not pathognomonic, the high-resolution CT finding of centrilobular, peribronchiolar, indistinct nodules should suggest the diagnosis of chronic hypersensitivity pneumonitis. PMID- 1414807 TI - Malignant pleural mesothelioma: value of CT and MR imaging in predicting resectability. AB - OBJECTIVE: Our objective was to determine if CT or MR imaging findings could be used to accurately predict resectability in patients with biopsy-proved malignant pleural mesotheliomas. SUBJECTS AND METHODS: CT and MR findings in 41 consecutive patients with malignant mesotheliomas who were referred to the thoracic surgery clinic for extrapleural pneumonectomy were studied by thoracic radiologists before surgery. Review of radiologic studies focused on local invasion of three separate regions: the diaphragm, chest wall, and mediastinum. Results of all imaging examinations were carefully correlated with intraoperative, gross, and microscopic pathologic findings. RESULTS: After radiologic and clinical evaluation, 34 patients (83%) had thoracotomy; 24 of these had tumors that were resectable. The sensitivity was high (> 90%) for both CT and MR in each region. Specificity, however, was low, probably because of the small number of patients with unresectable tumors. CONCLUSION: CT and MR provided similar information on resectability in most cases. Sensitivity was high for both procedures. Because CT is more widely available and used, we suggest it as the initial study when determining resectability. In difficult cases, important complementary anatomic information can be derived from MR images obtained before surgical intervention. PMID- 1414808 TI - Radiographic appearance of bullet tracks in the lung. AB - Penetrating missile or bullet wounds to the lung result in a number of abnormalities visible on chest radiographs. One finding that is unique to pulmonary parenchyma is the bullet track, which occurs along the course of a bullet as it traverses the lung. A bullet track may occur in the lung because of this organ's low specific gravity and high elasticity. In other tissues, such as liver and brain, that have higher specific gravities and lower elastic content, bullet tracks are rarely, if ever, noted because widespread destruction usually occurs. Bullet tracks may have a delayed appearance on chest radiographs, and thus may cause confusion in interpretation if a history of injury is not elicited. With the increase in violet confrontations in the United States, it is more and more likely that radiologists will be asked to interpret chest radiographs of patients who have had penetrating bullet injuries to the thorax. In this pictorial essay, we illustrate the appearance of bullet tracks in lung on chest radiographs. PMID- 1414809 TI - Bronchial stenosis due to endobronchial tuberculosis: successful treatment with self-expanding metallic stent. AB - Endobronchial tuberculosis is present in 10-40% of patients with active pulmonary tuberculosis, and more than 90% of the patients with endobronchial tuberculosis have some degree of bronchial stenosis. The primary treatment for tuberculous bronchial stenosis is antituberculous chemotherapy combined with steroids, but some patients do not respond well, and more aggressive treatment is needed to restore the patency of the involved bronchus. Balloon dilatation of tuberculous bronchial stenosis has been reported to be successful. However, in our experience, balloon dilatation of the stenotic segment has not significantly improved patients' clinical symptoms except in those with very short segmental stenosis. We describe a case of tuberculous bronchial stenosis that was successfully treated with Gianturco self-expanding metallic stents. PMID- 1414810 TI - Screening mammography in 350 women with breast implants: prevalence and findings of implant complications. AB - OBJECTIVE: A series of screening mammograms in asymptomatic women with breast implants was reviewed to determine the prevalence of clinically silent sequelae of breast augmentation and to analyze the mammographic findings. MATERIALS AND METHODS: The screening mammograms of 350 consecutive women with implants were reviewed retrospectively by experienced mammographers. Any women who reported problems had a diagnostic examination and therefore were not included in our sample. Mammographic features of sequelae specific to implantation such as development of a fibrous capsule, periprosthetic calcification, implant herniation, and silicone leaks were tabulated. Additionally, modified compression (push-back) views, when obtained, were evaluated for their usefulness. RESULTS: Fibrous encapsulation of breast implants was seen in 257 (73%) of 350 women. Periprosthetic calcification was seen in 90 (26%), and 60 women (17%) had implant herniations. Sixteen women (5%) had implant failure as evidenced by silicone leak. Two of these women had bilateral implant failures. Surgical confirmation was attainable in only five of 16 women. Analysis of modified compression views demonstrated an overall improvement in visualization of breast tissue with this technique. Although the sample size is small, there was a significant increase in the amount of breast tissue seen with push-back views in women with submuscular implants. CONCLUSION: Our analysis revealed a wide range of mammographic findings in this group of asymptomatic women with breast augmentation. Especially worrisome is the 5% prevalence of unsuspected silicone extravasation. Additionally, we have demonstrated the usefulness of push-back views in this screening group, especially in women with submuscular implants. PMID- 1414811 TI - Meckel's diverticulum. PMID- 1414812 TI - Percutaneous obliteration of the cystic duct with a holmium:yttrium-aluminum garnet laser: results of in vitro and animal experiments. AB - OBJECTIVE: The purpose of this study was to investigate the feasibility of using a holmium:yttrium-aluminum-garnet laser to permanently occlude the cystic duct in order to isolate the gallbladder from the biliary-enteric circulation and prevent gallstone formation. MATERIALS AND METHODS: To determine the optimal laser parameters (power and pulsing rate) for cystic duct thermocoagulation, 20 freshly excised porcine gallbladders with intact cystic ducts underwent low-energy (0.075 0.085 J/pulse) or high-energy (0.20-0.25 J/pulse) thermocoagulation. Histopathologic examination was done to determine the extent of cystic duct injury. After in vitro experiments, percutaneous transcholecystic laser thermocoagulation of the cystic duct was performed on 23 anesthetized domestic pigs (four controls). Cholangiograms immediately after laser thermocoagulation were obtained to assess cystic duct occlusion. Animals were sacrificed for histopathologic correlation immediately after laser thermocoagulation (n = 4), 72 hr later (n = 4), and 6 weeks later (n = 15). RESULTS: In the in vitro studies, all 10 cystic ducts in the high-energy group were occluded, while only four in the low-energy group were occluded. At histology, all cases in both groups showed circumferential injury to the cystic duct wall without injury to the cystic artery or vein. In the in vitro experiments, the cystic duct was successfully cannulated in 21 (91%) of 23 animals. Cholangiography after thermocoagulation showed occlusion of the cystic duct in 16 (84%) of 19 cases. Immediately after laser thermocoagulation, the cystic duct mucosa was circumferentially destroyed, whereas after 72 hr necrosis of the cystic duct wall and periductal tissues had occurred. By 6 weeks, all pigs had complete cystic duct fibrosis without injury to the common bile duct. CONCLUSION: Holmium:yttrium-aluminum-garnet laser thermocoagulation of the cystic duct can be performed easily, results in immediate cystic duct occlusion, and leads to permanent fibrous ductal obliteration by 6 weeks. PMID- 1414813 TI - Cathode rays and controversy. PMID- 1414814 TI - Percutaneous chemical gallbladder sclerosis after laser-induced cystic duct obliteration: results in an experimental model. AB - OBJECTIVE: Chemical gallbladder sclerosis has been attempted as a way to defunctionalize the gallbladder in patients who have undergone nonsurgical removal of gallstones and who are unable to undergo surgical/laparoscopic cholecystectomy. The purpose of this investigation was threefold: to study an animal model for chemical sclerosis of the gallbladder with 95% ethanol and 3% sodium tetradecyl sulfate, to attempt chemical sclerosis immediately after percutaneous cystic duct obliteration by laser thermocoagulation, and to assess histopathologic changes in the gallbladder after sclerosis. MATERIALS AND METHODS: Percutaneous cholecystostomy and laser thermocoagulation of the cystic duct was performed in 13 pigs. Eight pigs underwent immediate gallbladder sclerosis with 95% ethanol and 3% sodium tetradecyl sulfate while two pigs received 95% ethanol only. The remaining three pigs served as controls. The cholecystostomy catheter was removed immediately after the procedure. All animals were sacrificed 6 weeks after laser thermocoagulation. Multiple sections through the gallbladder, which included the adjacent liver, the cystic duct, and the common bile duct, were obtained for histologic examination. RESULTS: At autopsy, the gallbladder in all 10 animals who underwent gallbladder sclerosis was reduced in size compared with controls. In all treated animals, the gallbladder mucosa was denuded; however, in nine of 10 cases reepithelialization had occurred. Complete sclerosis without reepithelialization was achieved in one pig who received both ethanol and sodium tetradecyl sulfate. In the two animals who received ethanol only, the depth of wall necrosis around the gallbladder lumen was less than in those pigs who received both ethanol and sodium tetradecyl sulfate. No pigs showed signs of hepatic necrosis or injury to the common bile duct. CONCLUSION: Cystic duct laser thermocoagulation allows immediate gallbladder sclerotherapy without injury to the common bile duct. Sclerosis with ethanol and sodium tetradecyl sulfate results in denudation of the gallbladder mucosa. However, a single therapeutic session with immediate removal of the cholecystostomy catheter was inadequate for gallbladder ablation in this model because of reepithelialization. PMID- 1414815 TI - Use of T1-weighted MR imaging to differentiate between primary polydipsia and central diabetes insipidus. AB - PURPOSE: To investigate the value of MR in differentiating patients with primary polydipsia, who have an intact neurohypophyseal system, from those with central diabetes insipidus, who have impaired synthesis and/or release of vasopressin. METHODS: Eighteen patients with clinically significant hypotonic polyuria were diagnosed endocrinologically as having primary polydipsia or diabetes insipidus (central or nephrogenic). These patients, and 92 patients without sellar disease, were then imaged with 1.5-T, T1-weighted, thin sagittal sections without gadolinium contrast. RESULTS: Normal hyperintense signal of the neurohypophysis was present in 90 of 92 patients without sellar disease. The signal was also present in all six patients with primary polydipsia. In contrast, the hyperintense signal was absent in all eight patients with central diabetes insipidus. Three of the four patients with nephrogenic diabetes insipidus also had an absent hyperintense signal. CONCLUSION: T1-weighted MR may prove important in differentiating patients with central diabetes insipidus from those with primary polydipsia. PMID- 1414817 TI - MR of the pituitary gland: functional imaging? PMID- 1414816 TI - Macroprolactinomas: serial MR imaging in long-term bromocriptine therapy. AB - PURPOSE: To study the changes in macroprolactinomas during long-term bromocriptine therapy by means of serial MR imaging, and to correlate the findings to the serum prolactin (S-PRL) levels. PATIENTS AND METHODS: Thirteen patients with macroprolactinomas were studied before and during bromocriptine therapy; six to 11 MR examinations were performed with a duration of follow-up of 22 to 74 months. Tumor size, extension, relationship to adjacent structures, and signal intensity patterns were evaluated. Signal intensity ratios and T2 values were calculated in areas of apparently solid tumor tissue. RESULTS: Bromocriptine effectively reduced the size of all tumors; the size reduction was already significant at 1 week, but often continued for several years. Reenlargement during therapy was seen in three cases. The development of chiasmal herniation parallel to increasing cisternal invagination into the sella was a common finding, but was not correlated to visual symptoms. Signal intensity patterns corresponding to hemorrhage, cysts or necrosis were frequently observed, and transitions from one pattern to another were common. Hemorrhage occurred mainly in tumors corresponding to high initial serum prolactin levels. After 1 year of therapy, there was a significant increase in T2 values, indicating an increased water content in residual solid tumor tissue. CONCLUSIONS: MR is valuable for follow-up in bromocriptine therapy of macroprolactinomas, and provides new information on the tumor size changes, the inner structure of the tumors, and the optic chiasm. PMID- 1414818 TI - MR assessment of pituitary gland morphology in healthy volunteers: age- and gender-related differences. AB - PURPOSE AND METHODS: High-field MR images at 1.5 T were used to characterize the effects of age and gender on pituitary size and shape in a sample of 71 adult volunteers (40 females), aged 21 to 82 years. FINDINGS: For all subjects, age was inversely correlated with pituitary height (r = -.43, P less than .0002) and cross-sectional area (r = -.35, P less than .0028). Age-specific gender differences were also present in pituitary height and area. A convex upper pituitary margin was more common in females (P = .002) and younger subjects (P = .009). CONCLUSIONS: This study confirms that aging is accompanied by gender specific changes in pituitary size and shape, and provides normative data that may facilitate evaluation of the pituitary gland in neuroendocrine disorders. PMID- 1414819 TI - Magnetic susceptibility artifact in spin-echo MR imaging of the pituitary gland. AB - PURPOSE: To evaluate the magnetic susceptibility effect on spin-echo MR images of the pituitary gland. METHODS: Air-in-water phantom experiments and studies in normal volunteers were performed using various sampling bandwidth (8.3-33.3 kHz) spin-echo sequences with the polarity of the readout gradient normal or reversed. RESULTS: Attachment of a sphenoid septum to the sellar floor was the major factor in the appearance of the inferior surface of the pituitary gland. Patterns of distortion and/or artifactual signal intensities, related to the presence or absence of the attachment, were accentuated on the images with narrower bandwidth. A "spearhead shape" deformity of the sphenoid sinus was observed both in the air-in-water phantom experiment, and when no sphenoid septum was present. When a sphenoid septum was present, two spearhead shapes side by side were present. High-intensity artifacts were seen where the sellar floor was misplaced into the pituitary gland. CONCLUSION: Knowledge of the patterns of distortion and high-intensity artifact is important in the diagnosis of pituitary lesions. PMID- 1414821 TI - Dysembryoplastic neuroepithelial tumors: MR appearance. AB - PURPOSE: Dysembryoplastic neuroepithelial tumor (DNT) is a newly described, pathologically benign tumor arising within the supratentorial cortex and having a 100% association with partial complex seizures. We reviewed the MR appearance of the brains of six patients with DNT, without and with administration of gadolinium-DTPA, emphasizing the clinical and radiologic features. METHODS: The MR images in six patients (five male, one female) with pathologically proved DNT were reviewed. Five had partial complex seizures and one had partial simple seizures. Age at onset of partial seizures ranged from 2 to 19 years. Scans were obtained with conventional T1 and T2 weighting without and with the administration of gadolinium-DTPA. All patients had craniotomies for medically refractory seizures and pathologic examination of all specimens was available for review. RESULTS: MR demonstrated a focal cortical mass in all patients. Five were located in the temporal lobe and one was located within the occipital lobe. Two showed enhancement with gadolinium-DTPA. Calcification occurred in one lesion. Common features included very low signal intensity on T1-weighted images and high signal on T2-weighted images, similar to cerebrospinal fluid. Proton density images demonstrated slightly higher signal intensity in the lesion than cerebrospinal fluid. The margin of the tumor is well-circumscribed and may remodel the adjacent calvarium. CONCLUSIONS: DNT, a newly described pathologic entity resulting in chronic, often medically, intractable seizures, has characteristic features on MR that allow it to be suggested in the differential diagnosis. These lesions may simulate benign cysts; however, increased signal intensity on proton density images should prompt further investigation in the proper clinical setting. Differentiation from low-grade astrocytomas and ganglioglioma is not possible by MR. PMID- 1414822 TI - Intracranial fetus-in-fetu: CT diagnosis. AB - The authors present a case of fetus-in-fetu in which the CT findings are compatible with an earlier description by Nocera et al., i.e., a "round or tubular collection of very low density fat surrounding a central bony structure (probably one of the legs)." Additionally, sonography showed a heterogeneous mass with limb-like structures in the left lateral ventricle. Plain films can confirm the presence of a vertebral column and identify specific bony structures, but CT is a valuable aid in cases where plain films were not obtained or are inconclusive. PMID- 1414820 TI - Can nonenhancing white matter lesions in cancer patients be disregarded? AB - PURPOSE: To assess the risks and implications of assuming that white matter lesions in cancer patients that do not enhance with gadopentetate dimeglumine (Gd DTPA) can be considered to be benign. METHODS: Gd-DTPA was administered prospectively to 131 consecutive patients with biopsy-proved extracranial malignancies referred for cranial MR imaging to exclude cerebral metastases over a 21/2-year period. From this initial group, 50 patients were identified who had focal nonenhancing lesions of the white matter on T2-weighted images, but no other findings to suggest metastatic disease. This cohort of 50 patients was then followed for at least 1 year to determine the risk and clinical implications of assuming these nonenhancing white matter lesions were benign. RESULTS: Thirty patients (60%) were alive and clinically free of cranial metastatic disease at least 1 year following their initial MR study (median follow-up time, 17 months). Twenty of the 50 patients (40%) died within 1 year of their study (median survival, 4.1 months). Review of clinic notes and hospital charts revealed no evidence for deterioration of neurologic status in any of these patients before death, and the cause of death in each case was ascribed to extracranial complications of their systemic malignancies. Eight of these 20 patients who expired had at least one follow-up cranial CT or MR scan before death showing no new cerebral metastases or change in the nonenhancing white matter lesions previously identified. In a single patient, however, follow-up MR scan revealed conversion of one of her several white matter lesions from nonenhancing to enhancing without appreciable change in its size on T2-weighted images. Unfortunately, this patient died 4 months later from surgical complications without interval change in her neurologic status nor pathologic proof of the nature of this lesion. CONCLUSIONS: White matter lesions in cancer patients that do not enhance with Gd-DTPA at the time of the initial MR study have a low probability of representing metastatic disease. Clinical management or final outcome will not likely be altered by assuming such lesions are benign. PMID- 1414823 TI - Pleomorphic xanthoastrocytoma. AB - We report two cases of pleomorphic astrocytoma, a rare primary brain tumor with an unusually good prognosis. These lesions typically are peripherally located, partially cystic, temporal lobe masses. Dural attachment is frequent, calcifications are not. Angiography usually shows a hypovascular mass, although blood supply from the external carotid artery may be seen. PMID- 1414824 TI - Totally cystic schwannoma of the tenth cranial nerve mimicking an epidermoid. PMID- 1414825 TI - Subdural hygroma versus atrophy on MR brain scans: "the cortical vein sign". AB - PURPOSE: To determine if the position of the superficial cerebral cortical veins can be used to distinguish subdural hygroma from atrophy on MR brain scans. METHODS: Retrospective review of MR scans obtained in cases of extracerebral fluid collections, separating these into two groups, ie, subdural hygroma or atrophy. FINDINGS: All cases of atrophy in this study showed cortical veins and their branches traversing widened cerebrospinal fluid spaces over the cerebral convexities. None of the subdural hygroma patients showed this finding. Cortical veins in hygroma patients were seen only at the margin of the displaced cortex, and did not traverse the fluid collections over the cerebral convexities. CONCLUSIONS: The authors call the visualization of cortical veins and their branches within fluid collections at the cerebral convexities "the cortical vein sign." They believe this sign to be prima facie evidence of atrophy; its presence rules out the diagnosis of subdural hygroma in the region of interest. PMID- 1414826 TI - Systemic lupus erythematosus associated with marked intracranial calcification. AB - The authors describe a case of systemic lupus erythematosus associated with marked intracerebral calcification. The distribution of high signal on T1 weighted MR images was almost identical to the distribution of calcification on CT; however, the bodies of caudate nuclei with little calcification on CT also showed high intensities on T1-weighted images. PMID- 1414827 TI - Radiologic-pathologic correlation: hemangioblastoma. PMID- 1414828 TI - Primary meningeal tumors in children: correlation of clinical and CT findings with histologic type and prognosis. AB - PURPOSE: To identify the radiologic features that might help in preoperative differentiation of the meningiomas from the remaining primary meningeal tumors, in particular the malignant tumors. METHODS: The clinical and computed tomographic features of 21 children with histologically proved primary meningeal tumors were analyzed. FINDINGS: Benign tumors (meningiomas) are more likely to occur in older children, to have longer symptom duration, and to have CT appearances similar to the "typical" adult meningioma. Atypical CT features suggest a malignant meningeal tumor, such as meningeal sarcoma, melanoma, or meningeal primitive neuroectodermal tumor. The recent identification of a new subtype of meningioma (a "sclerosing" group) is discussed. This is common in children and the CT and clinical features are similar to those seen in other meningiomas. It is frequently mistaken histologically for an intraaxial tumor, or for an atypical or malignant meningioma. These sclerosing meningiomas may also show brain invasion but despite this, in the short term, the prognosis is no different from other meningiomas. CONCLUSION: The bad reputation previously ascribed to childhood primary meningeal tumors should be confined to that small group that are malignant. Meningiomas have a more favorable outlook. PMID- 1414830 TI - Delayed neurologic deterioration in the patient with spinal trauma: role of MR imaging. AB - PURPOSE: To 1) correlate spinal MR features and modes of clinical presentation associated with symptomatic neurologic deterioration following longstanding spinal trauma; 2) correlate degree of neurologic deficit with spinal MR appearance in these patients; and 3) determine the relationship between new symptoms and ongoing cord compression. METHODS: Retrospective examination of MR images, and correlation with clinical data, in 94 consecutive patients. RESULTS: Sixty-seven patients presented with either an increase in degree of myelopathy or ascending neurologic level. Spinal cord atrophy (43%), syrinx (41%), and cord compression (24%) were found most frequently. Whereas in patients with complete motor and sensory deficit cord atrophy was the most frequent finding (52%), 75% of patients with useful motor function had normal spinal cords. There was a significant association (P less than .05) between cord compression and the MR findings of cord atrophy and myelomalacia, whereas a normal cord was over twice as frequent in patients without spinal cord compression. MR imaging led to an active change in management in 15% of patients, with improvement following surgery in all operated cases. CONCLUSION: Although syrinx is a frequent, and treatable cause of delayed neurologic deterioration, MR will frequently show other abnormalities such as ongoing cord compression. MR imaging should be performed urgently in all patients with new symptoms to enable early treatment to prevent irreversible loss of function. PMID- 1414829 TI - MR of the hypothalamic-pituitary axis in Langerhans cell histiocytosis. AB - PURPOSE: To describe the MR findings in the hypothalamic pituitary area in children with Langerhans cell histiocytosis and to define those MR alterations especially associated with the risk of developing diabetes insipidus. METHODS: The hypothalamic-neurohypophyseal axis was studied by sagittal and coronal 1.5 T1 weighted MR imaging in 14 children with Langerhans cell histiocytosis (five with diabetes insipidus) and in 28 low-stature controls, ages 6-14 years. RESULTS: The pituitary stalk was thicker in seven/14 patients (three with diabetes insipidus) than in controls (P less than .05). Bright posterior pituitary signal was undetectable in children with diabetes insipidus and in one/9 without diabetes insipidus. CONCLUSIONS: Thickening of the hypothalamus and/or the pituitary stalk in the absence of the posterior pituitary bright signal is seen in children with Langerhans cell histiocytosis with overt diabetes insipidus. Those Langerhans cell histiocytosis patients without diabetes insipidus but showing thickened stalk with or without posterior pituitary bright signal could be at high risk to develop diabetes insipidus. PMID- 1414831 TI - Fast spin-echo imaging in the evaluation of intradural disease of the spine. AB - PURPOSE: Fast spin echo (FSE) images were compared with conventional images in 46 patients with intradural spinal disease to determine their accuracy in the detection and delineation of lesions. MATERIALS AND METHODS: The images were interpreted by two neuroradiologists, who read individually. A total of 720 blinded readings formed the basis for this evaluation. A gold standard for each patient was selected, based on the blinded readings of the conventional studies. RESULTS: In the sagittal plane, the FSE sequences were found to have an accuracy of 93% and 93% for the first reader and 93% and 85% for the second reader. For the axial plane, the corresponding figures were 86% and 82% for the first reader and 64% and 77% for the second reader. These figures compared favorably with conventional sequences. Similar delineation of lesions was noted in 78% of cases. In the remaining cases, there were no significant trends. CONCLUSION: Because of these findings, FSE sequences appear as accurate as conventional sequences. In this study, they were capable of supplanting conventional sequences in the evaluation of intradural pathology of the spine in the sagittal plane, although conventional sequences were still preferred in the axial plane. PMID- 1414832 TI - MR of slow CSF flow in the spine. AB - PURPOSE: To evaluate a slow-flow MR sequence in normal CSF flow and in CSF flow disturbance in cases of spinal stenosis. METHOD: The method was tested for flow sensitivity and applied to 67 sites of spinal canal compromise. RESULTS: Phantom studies show that flow can be depicted at a velocity of 0.5-1 mm/sec. On clinical images, stagnant CSF is black, flowing CSF is bright. Typically, in high-grade (90%-100%) stenosis, CSF above and below the site of spinal canal compromise (SCC) is black. With intermediate stenosis (50%-89%), CSF above the SCC remains white but becomes black distal to the SCC. Low-grade stenosis shows only localized flow disturbances. CONCLUSION: This easy-to-use sequence can solidify the MR diagnosis of high-grade stenosis when a distinct flow pattern is recognized. Flow patterns for intermediate and low-grade stenosis are less reliable. PMID- 1414833 TI - Herpes zoster myelitis: MR appearance. AB - The author describes a 71-year-old woman in whom cutaneous cervical herpes zoster was complicated by the development of cervical myelitis. T2-weighted MR showed two focal areas of hyperintensity in the cervical cord and suggested a slight enlargement at C2-C3 and C7. PMID- 1414834 TI - MR of extramedullary hematopoiesis causing cord compression in beta-thalassemia. PMID- 1414835 TI - Artifacts associated with MR neuroangiography. AB - Neurovascular MR angiography (MRA) is rapidly gaining greater clinical acceptance. To provide functional information, novel techniques of acquisition, information processing, and display are used, generating a new set of artifacts. The purpose of this paper is to outline the causes, provide examples, and note clinical problems associated with MRA artifacts by grouping them into six common types: 1) poor visualization of small vessels, 2) overestimation of stenosis, 3) view-to-view variations, 4) false positives, 5) false negatives, and 6) vessel overlap. This in turn will lead to four generalized solutions: 1) optimize acquisition parameters, 2) edit volume boundaries before performing maximum intensity projection reconstructions, 3) refer to the individual source images, and 4) use alternative image processing. By organizing and simplifying both clinical problems and solutions into major categories, a greater understanding of the current clinical indications and the overall goals of MRA can be achieved. PMID- 1414836 TI - MR angiography of the extracranial carotid arteries using a two-slab oblique 3-D acquisition. AB - PURPOSE: To describe an oblique, two-slab 3-D acquisition technique for MR angiography of the extracranial carotid arteries, an approach chosen to minimize saturation effects when the body coil is used as transmitter, as is often the situation when a dedicated neck coil is used as receiver. SUBJECTS: Five healthy subjects and 17 patients in whom carotid artery disease was suspected underwent MR angiography using the above technique. RESULTS: Flow contrast was much better than in direct sagittal acquisition. Comparisons between multislab transverse 3-D acquisition and the oblique approach showed that a greater length of the carotid arteries was depicted and scan time was less for oblique acquisitions. CONCLUSIONS: Use of oblique imaging is a simple and effective solution to the problem of coil-related saturation effects. PMID- 1414837 TI - Fat suppression in combination with multiple overlapping thin-slab 3-D acquisition MR angiography: proposed technique for improved vessel visualization. AB - PURPOSE: To study the parameters of the 1331 fat saturation pulse (saturation pulse flip angle (SPFA) and interpulse delay (tau)) in order to identify values that provide optimal vessel visibility. METHODS: Carotid bifurcations of three healthy subjects were studied. RESULTS: The optimal values for the SPFA and tau were 60 degrees (7.5 degrees, -22.5 degrees, 22.5 degrees, -7.5 degrees) and 2.0 3.0 msec, respectively. At these values there was a 1.56-fold increase (SD = +/- .12, P less than .01) in the contrast-to-noise ratio between the left internal carotid artery and fat compared to the study without fat saturation. A 3.0-fold increase was noted for the smaller left occipital artery. Additionally, there was no statistically significant reduction in the vessel-muscle contrast-to-noise ratio nor in the absolute vessel signal-to-noise ratio at these values. CONCLUSION: Implementation of fat saturation into carotid MR angiography markedly improves visualization of vascular anatomy without increasing imaging time. PMID- 1414838 TI - Determination of blood flow direction using velocity-phase image display with 3-D phase-contrast MR angiography. AB - The authors describe their use of phase-contrast MRA to depict vascular anatomy and to define the direction of blood flow. Documentation of flow reversal can provide information regarding prognosis and can facilitate surgical planning. The technique requires no additional scan-time. PMID- 1414839 TI - Non-heme mechanisms for T1 shortening: pathologic, CT, and MR elucidation. AB - PURPOSE: To further elucidate the nonparamagnetic effects of T1-relaxation mechanisms in MR imaging. PATIENTS AND METHODS: In 12 patients with lesions having hyperintense signal on T1-weighted spin-echo MR, findings were correlated with autopsy/surgical biopsy in seven cases and/or noncontrast CT scans in 10 cases. RESULTS: Eight of the 10 CT scans demonstrated hyperattenuation in the lesions, indicating mineralization, which correlated with the areas of hyperintense signal on MR. Histologic characterization of the mineralization was accomplished in three cases using four stains; hematoxylineosin, alizarin red S, von Kassa stains for calcium and Perls' iron. The areas of mineralization were homogeneously strongly positive with the calcium stains and only focally weakly positive with the Perls' iron stain. The mineralization was further characterized in all three cases as containing calcium and phosphorus using energy-dispersive x ray analysis. Four of the 12 cases had either no correlating CT scans (two cases) or the CT showed no hyperattenuating properties to the lesions (two cases). In all four of these cases, microscopic examination showed that the gyriform configuration of the cortical hyperintense signal on T1-weighted images correlated with linear zones of nonhemorrhagic laminar necrosis (cerebral infarction). No mineralization, except for an occasional ferruginated neuron, could be demonstrated with the four histologic stains. Specimen MR imaging of formalin-fixed brain sections in one case demonstrated in vitro the gyriform hyperintense signal seen in vivo. CONCLUSION: Our studies describe and pathologically characterize two associations with T1 shortening in neuroimaging unrelated to the presence of heme: 1) calcification and 2) laminar necrosis in cerebral infarction. PMID- 1414840 TI - Angiographic findings in two cases of aneurysmal malformation of vein of Galen prior to spontaneous thrombosis: therapeutic implications. AB - Two cases of aneurysmal malformations of the vein of Galen with later spontaneous thrombosis are reported. Angiograms before thrombosis in both cases showed mural type aneurysmal malformations of the vein of Galen with slow arteriovenous shunts and associated stagnation of contrast in the venous sac secondary to severe outflow restriction. Based on these angiographic findings, the patients were managed conservatively and the arteriovenous malformations of the vein of Galen thrombosed with good clinical outcomes. Twenty cases of spontaneous thrombosis previously reported in the literature are reviewed. PMID- 1414841 TI - Detachable leak balloon with IBCA/NBCA for treatment of aneurysm. PMID- 1414842 TI - MR angiography of cervical fibromuscular dysplasia. AB - The authors present examples of cephalic fibromuscular dysplasia (involving five vessels in two patients) using 2-D time-of-flight MR angiography and conventional angiography. Artifacts that can mimic the MR appearance of fibromuscular dysplasia will tend to decrease the sensitivity and specificity of MRA in its detection. PMID- 1414843 TI - Gd-DTPA enhancement of the cisternal portion of the oculomotor nerve on MR imaging. AB - PURPOSE: To describe a radiographic finding--enhancement of the cisternal portion of the third cranial nerve on postcontrast MR--and to correlate it with patients' clinical symptoms and ultimate diagnosis. MATERIALS AND METHODS: Thirteen consecutive patients with enhancement of the cisternal portion of the third cranial nerve on postcontrast MR were retrospectively identified; 50 control patients referred for pituitary microadenomas were also retrospectively reviewed. FINDINGS: The enhancement was bilateral in six patients and unilateral in seven patients. Four of the six patients with bilateral enhancement had unilateral oculomotor nerve palsies; none had bilateral third cranial nerve palsy. Five of the seven patients with unilateral enhancement had ipsilateral third nerve palsies. Of the nine patients with third nerve palsies, the pupil was involved in four patients. Follow-up studies were available in six patients, four of whom had third nerve palsy. Resolution of the enhancement correlated with resolution of the symptoms in two patients. The patients' underlying diagnoses were lymphoma (four), leukemia (one), viral meningitis (one), neurofibromatosis (two), inflammatory polyneuropathy-HIV related (one), ophthalmoplegic migraine (one), Tolosa-Hunt syndrome (one), coccidioidomycosis (one), and diabetes (one). No enhancement was seen in any of the controls. CONCLUSION: Enhancement of the cisternal segment of the third cranial nerve is always abnormal, revealing an underlying inflammatory or neoplastic process. However, it is not always associated with clinically apparent oculomotor nerve dysfunction. PMID- 1414844 TI - Proboscis lateralis with associated orbital cyst: detailed MR and CT imaging and correlative embryopathy. AB - Proboscis lateralis is a rare craniofacial malformation. We present a case in a 1 week-old male infant, describe the clinical and imaging findings, and discuss the pertinent embryology. MR and CT proved to be complementary: CT provided anatomic detail in bone, defined the nasal cavity, and aided in determining the relationship of the proboscis and orbit; MR clarified the relationship of the proboscis to the orbit and skull base, and the relationships of normal brain to the dysplastic ethmoid centers. PMID- 1414845 TI - AIDS-related CNS cryptococcosis: radiologic-pathologic correlation. AB - PURPOSE: This study evaluates the effectiveness of cranial CT and MR in detecting autopsy findings of AIDS-related CNS cryptococcosis. METHODS: Final imaging studies compared with pathology were CT in eight patients (five with contrast) and MR in five patients (all with Gd-DTPA). RESULTS: Neither modality effectively identified cryptococcal meningitis. Punctate hyperintensities were seen in all patients with MR and corresponded pathologically to both perivascular spaces dilated by cryptococcal infection and cryptococcomas. Pathologically, cryptococcomas were more common than dilated perivascular spaces. MR detected more cryptococcomas than did CT, but both modalities underestimated the number of lesions seen at autopsy. Contrast enhancement of cryptococcomas and cryptococcal meningitis was uncommon. CONCLUSIONS: CNS cryptococcosis was more effectively demonstrated by MR than by CT, but both modalities underestimated the pathologic extent of the disease. Cryptococcal lesion contrast enhancement was unusual possibly because of the immunocompromised state of our patients and the unique characteristics of the organism itself. PMID- 1414846 TI - Clostridium septicum meningoencephalitis: an unusual presentation of occult rectal carcinoma. PMID- 1414847 TI - Cerebral aspergillosis: MR imaging and histopathologic correlation. AB - The authors report a case of intracranial aspergillosis secondary to immunosuppression. Signal intensity changes in the lesion on brain MR are compared with gross and histopathologic findings at autopsy. A peripheral ring of low signal intensity relates to a dense population of Aspergillus hyphal elements and small areas of hemorrhage. CT findings are included for comparison. PMID- 1414848 TI - Prefrontal sonic treatment: MR findings. AB - The authors describe the use of MR in a patient who underwent prefrontal sonic treatment for relief of intractable headaches. MR demonstrated well-demarcated regions of encephalomalacia within the white matter of the frontal lobe (with relative sparing of cortex) in a characteristic conical volume that corresponded to the insonified regions. PMID- 1414849 TI - Curricula non medica. PMID- 1414850 TI - MR appearance of hypertrophic olivary degeneration: temporal relationships. PMID- 1414851 TI - Retroclival arachnoid cyst. PMID- 1414852 TI - Handgun control: a public health imperative. PMID- 1414853 TI - Biopsy of vertebral and paravertebral structures with a new coaxial system. PMID- 1414854 TI - Severe unilateral white matter involvement on MR: hypothetical association with dental pain and infection. PMID- 1414855 TI - MR imaging of various oxidation states. PMID- 1414857 TI - Comparison of in-house reference extracts of Dermatophagoides pteronyssinus and Phleum pratense with the WHO International Standards. AB - Two of the WHO First International Standards (IS) of allergenic extracts, the corresponding to Dermatophagoides pteronyssinus (House dust mite) and phleum pratense (Thymothy grass), have been used to assess the quality of our in-house reference preparations (IHR) and to calibrate their relative potency. The qualitative comparison was achieved by SDS-PAGE, Agarose-IEF and their respective enzime immunoblottings (Western blot and immunoprinting). The band patterns obtained were fairly similar for both Phleum pratense extracts. With the exception of two basic IgE binding proteins not detected in the IEF-blotting of the International Standard. However, several differences were noted between IS and IHR Dermatophagoides pteronyssinus extracts, indicating so the higher raw material heterogeneity. The difference was specially remarkable at the level of SDS-PAGE Immunoblotting since while our IHR extract showed similar ratio of Der p I to Der p II major allergens, the IS exhibited a large preponderance of Der p I, with Der p II allergen scarcely detected by our chromogenic method. Calibration of potency was done by means of RAST inhibition, therefore allowing the expression of our extract concentrations in International Units. The higher degree of homogeneity between Phleum pratense extracts was corroborated by the comparison of slopes from the RAST-inhibition plots. PMID- 1414856 TI - Cross-sectional area of nasal airways during the nasal provocation tests. AB - Eighteen patients with allergic rhinitis were studied using nasal challenge tests to allergens. The Rivron algorithm was used to evaluate results. We calculated the dose-area correlation and changes in the cross-sectional area of the nasal airway during the test. PMID- 1414858 TI - IgG4-anti-IgE antibodies in Chinese allergic children. AB - IgG4-anti-IgE antibodies have been identified in normal nonatopic subjects, as well as in allergic patients. Their potential role remains controversial. We studied 44 Chinese children with allergic symptoms, and measured their IgG4-anti IgE serum levels using a modified IgG4 FAST assay. The levels of IgG4-anti-IgE antibodies did not correlate with clinical status. The usefulness and relevance of these measurements remain questionable in allergic patients. PMID- 1414859 TI - Topical flunisolide treatment of perennial rhinitis: clinical and immunological effects. AB - We studied the clinical and immunological effects of three months' treatment with intranasal flunisolide (100 micrograms daily) in 18 allergic patients with perennial rhinitis. 17 were hypersensitive to house dust mite and one to Parietaria pollen only. We found no significant changes in white blood cell count, serum levels of IgE and nasal IgA. However the treatment induced a marked improvement of clinical symptoms in all cases, and we observed a significant reduction of total IgE in nasal secretion. Flunisolide seems to exert this effect through its antiinflammatory action on the nasal mucosa. PMID- 1414861 TI - Primary causes of medical instability of Medicare patients at discharge 1990 1991. AB - BACKGROUND: HCFA-sponsored Peer Review Organizations nationwide have been criticized by organized medicine, Medicare beneficiaries and interested Congressional parties for being punitive without exploiting educational opportunities garnered through their massive data collection capabilities. Until now this data has been poorly analyzed and has not been adequately utilized as a positive motivational tool. METHODS: HCFA has developed, with the cooperation of the medical community, six generic screens for Peer Review Organizations to utilize when evaluating quality care provided Medicare beneficiaries in an acute care setting. Through the sheer volume of cases seen, significant inpatient information can be obtained that cannot be duplicated in any other epidemiological endeavor. Line item discrepancies can be further studied through small-area-analysis to determine "who" as well as "what" may be the problem. RESULTS: By compiling and reviewing data in a systematic manner over two years (1990-1991), the Alabama Quality Assurance Foundation (AQAF) has singled out problems with patient medical stability at discharge as the predominant concern for care providers and reviewers alike. CONCLUSIONS: Having determined the primary problem in rendering quality care in a Prospective Payment System to Medicare beneficiaries lies in premature discharges, subsequent small-area analysis further narrows the focus of concerned individuals. Hopefully, practitioners and providers alike will act on their own initiative in correcting this problem. Follow-up review will be utilized to assure this self-corrective action. PMID- 1414860 TI - Interleukin 2 proliferative response by cord blood mononuclear cells of term and preterm neonates. AB - The results of previous studies on the proliferative response of resting cord blood mononuclear cells (CBMC) of term neonates to human recombinant interleukin 2 (hrIL-2) are contrasting. Some authors have reported a good and others a poor response. In our study we have obtained a significant reactivity, compared with the response of resting peripheral blood mononuclear cells (PBMC) of adult subjects, of resting CBMC to varying quantities of hrIL-2 in the absence of any known mitogenic or antigenic stimuli. Most responding cells was CD3 positive. Both CD4-positive and CD8-positive cells responded. However, we observed a more marked increase of the percentage of the CD4-positive T cells and a clear reduction of the percentage of the CD21-positive cells (B-lymphocytes) testing CBMC rather than PBMC of the adult subjects. The percentage of the NK cells was reduced in both the categories of subjects. Moreover, we have examined the reactivity to hrIL-2 of CBMC of preterm neonates. The results showed that this response is low. The peculiar level and kinetic of CBMC proliferative response to hrIL-2 are discussed. PMID- 1414862 TI - How PRN assists the physician, the patient and the board of medical examiners. PMID- 1414863 TI - Complacency, apathy, hostility. PMID- 1414864 TI - Minority, poor, and deaf. PMID- 1414865 TI - Improvements in the signing skills of hearing parents of deaf children. AB - Most deaf children are born to hearing parents. Yet, many hearing parents are unable to communicate clearly and unambiguously with their deaf offspring. This study looked at changes in the number of parents of deaf offspring who learn sign language, and the signing skills of those parents. It found that over the years the signing skills of these parents have been improving. Of the younger deaf offspring in this study, 73% reported that their parents knew some sign language. Younger offspring rated their parents' signing skills higher than did older offspring. These results may indicate that more parents are now learning sign language. PMID- 1414866 TI - How successful deaf teenagers experience and cope with isolation. AB - This study examined isolation among a group of deaf high school students who were nominated as "outstandingly successful" by their schools in a stratified random sampling from across the United States. From the data contained in 23 case studies, we determined that most of the students, whether from mainstream or residential programs, experienced some degree of isolation from peers or family or both. Nevertheless, most of the students had developed, or had at their disposal, positive strategies for coping with their isolation. These strategies are discussed and implications are drawn for teachers and parents. PMID- 1414867 TI - Recall performance on a central-incidental memory task by profoundly deaf children. AB - Bebko (1984) reported that deaf children tend not to use spontaneously active memory strategies such as rehearsal in tasks requiring recall of ordered, temporal information. The present study investigated whether this tendency is task specific or generalized to other experimental paradigms. A central incidental paradigm was used with profoundly deaf children and hearing children 6 to 13 years of age. The results for the hearing students replicated previous studies: central recall increased with age, but incidental recall changed little. For the deaf children, the results initially appeared very similar to those of the hearing children. However, on closer examination, the rehearsal strategies of the deaf students seemed less effective in mediating their recall. They apparently compensated for these difficulties by capitalizing on unique spatial features of the task, leading to recall levels comparable to those of the hearing students. Therefore, similar performance may not have been the result of equal strategy use but, rather, of the use of additional strategies by the deaf students. This study reinforced the need to provide additional training for deaf students in the use of memory strategies such as rehearsal when information is to be remembered in a sequential manner. PMID- 1414868 TI - Some concerns about using whole language approaches with deaf children. AB - The whole language philosophy is having an impact not only in general education but in the education of deaf children as well. Many of the practices derived from this philosophy are beneficial for all children. Yet, because most deaf children have tremendous difficulty in acquiring English literacy, a more direct approach to teaching them may be warranted in many cases. The field of deaf education would be better served if, rather than moving from one trend in general education to another, we first took into account the special needs of deaf learners and then worked systematically and deliberately to build a knowledge base of the most effective practices for promoting literacy. PMID- 1414869 TI - The Garden Cafe. An experiment in vocational education in the Philippines. AB - The author visited Bohol, a picturesque island in the Philippines 350 miles south of Manila, in 1986 and 1990 to observe and record the emerging deaf culture. Before the Peace Corps started a school program on the island some eight years ago, deaf children grew up functionally illiterate. Those who have not been found and are not enrolled in the fledgling school program still do, as they are completely isolated from the deaf community. This article describes heroic efforts to teach vocational skills to the deaf in Bohol. The project not only succeeded but led to the island's best restaurant, The Garden Cafe. PMID- 1414870 TI - Cumulative trauma disorders among educational interpreters. Contributing factors and intervention. AB - Upper extremity cumulative trauma disorders became a potentially significant occupational hazard among sign language interpreters at the National Technical Institute for the Deaf in the 1988-89 academic year. The following case control study was conducted to identify factors that might play a role in developing, exacerbating, and maintaining upper extremity cumulative trauma disorders among interpreters. Investigations were conducted to determine whether medical status, physical capacities, interpreting styles, pain, fatigue, and job stress differed among NTID's sign language interpreters. This report provides a general summary of selected findings as well as a conceptual framework that should help clarify the factors associated with upper extremity cumulative trauma disorders in sign language interpreters. The results indicated that the upper extremity cumulative trauma disorder diagnosed most often is tendinitis rather than a nerve entrapment syndrome (e.g., carpal tunnel syndrome). Analysis of the frequency of potential biomechanical risk factors indicated that those reporting pain demonstrated higher frequency of hand and wrist deviations from the neutral position, higher frequency of the upper extremities leaving a predefined work space, fewer rest breaks during interpreting sessions, and higher evaluator ratings of pace of finger and hand movements. Specific features of interpreting styles were associated with increased pain and fatigue. PMID- 1414871 TI - Deaf adolescents who drop out of local public schools. AB - This paper looks at correlates of school attrition in local public school programs. A preliminary survey of attrition and background data on a national sample of 451 deaf adolescents concluded that many of the same factors, including individual ability, local educational values, and certain demographic traits, that predict attrition in general education also apply to deaf education. The movement of students out of their original programs for whatever reason was primarily a regional phenomenon. Programs in the Southeast and the Southwest lost more of their original groups of students than did programs in the Northeast, Midwest, or Far West. The regional variations noted in our data suggest that local values about schooling will influence school attrition in local public school programs for the deaf. PMID- 1414872 TI - Attitudes toward deafness. A collegiate perspective. AB - The Rochester Institute of Technology is a unique environment; a large number of hearing-impaired students are enrolled on a predominately hearing campus. The authors of this article explored the integration of deaf and hearing students on the campus and the attitudes surrounding deaf-hearing relationships. The major factors that hearing students identified as contributors to positive interaction between the two groups included awareness of cultural diversity, communication sensitivity and development of effective communication skills, structured opportunities for interaction, and mutual accommodation and respect. PMID- 1414873 TI - Spontaneous remission of acute sarcoid myositis. PMID- 1414874 TI - Cysticercosis. PMID- 1414875 TI - STFM family practice recruitment. PMID- 1414876 TI - The primary physician: keeping no gates. PMID- 1414877 TI - Simple technique for removing foreign objects from the nose. PMID- 1414878 TI - The ABCs of DRGs. PMID- 1414879 TI - Urban family medicine: lost horizon or last frontier? PMID- 1414880 TI - Diary of a week in practice. PMID- 1414881 TI - No-scalpel vasectomy: a technique for family physicians. AB - Family physicians frequently perform outpatient vasectomies. A new approach to exposing the vas deferens, called the no-scalpel vasectomy, results in fewer complications and, the authors believe, improved patient acceptance. This technique, which calls for two specialized instruments, is described, along with patient selection and education issues, vasal occlusion techniques and post vasectomy follow-up. PMID- 1414882 TI - Erythema multiforme. AB - Erythema multiforme is a cutaneous reaction pattern manifested by well-demarcated plaques on the trunk and extremities. Target, or "iris," lesions, with central clearing, are characteristic of this disorder. Erythema multiforme may be a mild condition (erythema multiforme minor), or it may be a severe, possibly life threatening condition (erythema multiforme major or Stevens-Johnson syndrome). Toxic epidermal necrolysis, manifested by widespread epidermal desquamation, is the most severe form of this disorder. The three most common triggers for erythema multiforme are herpes simplex infection, mycoplasma infection and drug reactions. Drugs that can precipitate erythema multiforme include sulfonamides, penicillins, phenylbutazone and phenytoin. The appearance of the characteristic lesion is usually diagnostic. However, conditions such as tinea corporis, lupus erythematosus, herpetic gingivostomatitis, Behcet's disease and erosive lichen planus, among others, may mimic erythema multiforme. For mild cases, treatment is supportive, with antibiotics used for secondary skin infections. For severe causes, many physicians use systemic corticosteroids, although this treatment is not universally endorsed. PMID- 1414883 TI - Growth plate injuries: Salter-Harris classification. AB - Fracture of the growth plate is an injury unique to childhood. Most such fractures heal without permanent deformity. A small percentage, however, are complicated by growth arrest and subsequent deformity. The Salter-Harris classification of growth plate injuries aids in estimating both the prognosis and the potential for growth disturbance. The Salter-Harris system classifies growth plate fractures into five groups: type I, fracture through the growth plate; type II, fracture through the growth plate and metaphysis; type III, fracture through the growth plate and epiphysis; type IV, fracture through the growth plate, epiphysis and metaphysis, and type V, crush or compression injury of the growth plate. PMID- 1414884 TI - Cleft lip and cleft palate. AB - The birth of a child with a cleft lip or a cleft palate, or both, can be traumatic to the family. Although referral to a multidisciplinary team experienced in craniofacial abnormalities is essential, the family physician can reduce the impact on the family by providing antenatal diagnosis and continued care of the entire family after diagnosis, during initial feeding and bonding difficulties and throughout the many years of surgical and speech therapy. PMID- 1414885 TI - New drug offers alternative treatment for PCP. PMID- 1414886 TI - FDA approves clinical studies of silicone breast implants. PMID- 1414887 TI - HIV seroprevalence in cardiac arrest patients. PMID- 1414888 TI - Effects of angiotensin-converting enzyme inhibitors on tissue renin-angiotensin systems. AB - The renin-angiotensin system (RAS) plays a major role in the control of blood pressure and cardiovascular homeostasis and is involved in the pathogenesis of a number of cardiovascular disorders. The efficacy of angiotensin-converting enzyme (ACE) inhibitors in the treatment of hypertension and congestive heart failure has led to the widespread clinical use of ACE inhibitors in primary or secondary prevention of heart disease. The demonstration of the expression of the components of the RAS in several extrarenal tissues, as well as local generation of angiotensin II, has confirmed the existence of a tissue RAS that may serve organ-specific functions and act independently from the plasma RAS. The concept of paracrine/autocrine functions of the local RAS has changed our understanding of the functions of the RAS and suggests that tissue ACE inhibition may be of greater importance than inhibition of circulating ACE in the treatment of congestive heart failure and other cardiovascular disorders. Whereas the circulating endocrine RAS appears to be responsible for mediation of acute effects, the tissue RAS seems to be involved in more chronic situations, such as secondary structural changes of the cardiovascular system, and therefore could contribute to the pathogenesis of hypertension as well as other cardiovascular disorders, such as cardiac hypertrophy, coronary artery disease, and atherosclerosis. Several experimental and clinical findings suggest that reversal of cardiovascular structural changes secondary to cardiovascular disease and enhancement of renal sodium excretion by ACE inhibitors are important long-term antihypertensive actions possibly mediated by inhibition of the tissue RAS. PMID- 1414889 TI - Heart failure in 2001: a prophecy. AB - Understanding of heart failure has developed through 3 paradigms involving organ, cell, and gene. The first views heart failure as an abnormality of organ (pump) function leading to salt and water retention and vasoconstriction. Therapy to correct these circulatory abnormalities is well accepted and effective. The second considers heart failure as a disordered cellular function, mainly impaired contraction and relaxation. Efforts to correct the biochemical and biophysical abnormalities responsible for these disorders of myocardial performance have, however, been less successful. Recent emphasis on efforts to improve prognosis as well as symptoms in patients with chronic heart failure demonstrates that it is a lethal disease with problems of survival similar to those in malignancies. The third paradigm of abnormal gene expression, which in the failing heart represents a cardiomyopathy of overload, appears to be a major cause of poor prognosis in these patients. Evidence that the angiotensin-converting enzyme inhibitors have important effects on cell growth, as well as on vascular tone, suggests that their ability to prolong survival in patients with heart failure may be due largely to the inhibition of detrimental effects of angiotensin II on cardiac gene expression. Thus, it seems likely that work focused on the third paradigm will uncover specific abnormalities of gene expression that are responsible for poor survival of patients with heart failure. By 2001, I predict that heart failure will be viewed as an abnormality of cell growth and this will lead to the development of therapies to retard, if not reverse, the clinical deterioration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414890 TI - Results of the treatment trial of the studies of left ventricular dysfunction (SOLVD). The SOLVD Investigators. PMID- 1414891 TI - Ventricular remodeling following myocardial infarction. AB - Ventricular remodeling denotes structural changes that occur in ventricular chamber size, wall thickness, and composition following myocardial damage. Following acute coronary occlusion, there are various factors to consider at different times that may contribute to subsequent ventricular dilation. Early infarct expansion and later healing may be accompanied by compensatory hypertrophy in the noninfarcted region and progressive global dilation, that may progress long term, the major stimulus being increased wall stress. The 2 major factors influencing ventricular remodeling following myocardial infarction are infarct artery patency and the ventricular loading conditions. Thrombolytic therapy may produce coronary reperfusion and limit infarct size. Patency of the infarct-related artery may also provide later benefits for ventricular remodeling. Following infarct evolution, pharmacologic intervention provides the potential to minimize the sequelae of infarct expansion and ventricular dilation. Clinical studies indicate that treatment of symptomless left ventricular dysfunction with angiotensin-converting enzyme inhibition at greater than or equal to 1 week following myocardial infarction may prevent further ventricular dilation and reduce the probability of progression to heart failure. Earlier intervention, at 24-48 hours following Q-wave myocardial infarction, is also practicable and effective. Even earlier intervention, in combination with or immediately following thrombolysis, is being assessed in other studies. The timing of treatment is of considerable importance because blockade of compensatory mechanisms activated at the time of infarction may not be desirable immediately, even though these mechanisms may be deleterious later. The results of large-scale mortality studies are awaited to indicate the benefit of this type of treatment in terms of heart failure prevention and survival long term. PMID- 1414892 TI - Prospects for cardioreparation. AB - The structure of the myocardium has 2 principal components, a myocytic compartment and a non-myocytic compartment that consists primarily of interstitial tissue. It appears that increased collagen production is mainly responsible for the functional consequences of structural remodelling. The concept of cardioreparation implies both a restoration of structural abnormalities and a return of cardiac function to or toward normal. In spontaneously hypertensive rats with left ventricular hypertrophy and adverse structural remodeling of the cardiac interstitium, angiotensin-converting enzyme inhibition has resulted in restoration of myocardial integrity and stiffness toward normal. Further research needs to be undertaken to identify the molecular mechanisms involved in the development of interstitial myocardial fibrosis, and reliable methods for assessing the interstitium and the changes that occur within it in clinical practice need to be developed. PMID- 1414893 TI - Ventricular arrhythmias in heart failure. AB - Heart failure is an increasingly common disorder leading to reduced quality and expectancy of life. Asymptomatic and symptomatic ventricular arrhythmias are a frequent complication and have been found to be independent prognostic predictors for sudden cardiac death in patients with heart failure. Unfortunately, the positive predictive failure for this finding is low, but in patients with sustained ventricular arrhythmias, variables indicating impaired pump function are the most important predictors of sudden and of nonsudden cardiac death. Arrhythmias in heart failure may have many different underlying mechanisms. Indications for, and mode of treatment of, arrhythmias in heart failure depend on the symptoms and prognostic significance of the arrhythmia. Primarily, pump function should be optimized and antiarrhythmic drug therapy instituted only when the arrhythmia persists. In poorly tolerated and life-threatening arrhythmias, implantable devices allowing pacing and defibrillation must be considered. No data are presently available indicating a protective role of antiarrhythmic drugs in the prevention of sudden cardiac death in heart failure. Future directions should concentrate on the development of better stratification of risk for sudden death, better delineation of mechanisms of arrhythmias in heart failure (allowing the development of mechanism-specific antiarrhythmic drugs), and research into new nonpharmacologic techniques such as cardiomyoplasty and molecular biologic techniques to rebuild the failing heart muscles. PMID- 1414894 TI - Electrolyte balance in heart failure and the role for magnesium ions. AB - It is well established that clinically significant changes in a number of electrolytes occur in patients with congestive heart failure (CHF). Magnesium ions are an essential requirement for many enzyme systems, and evidence is rapidly emerging that magnesium deficiency is a major risk factor for survival of CHF patients. In animal experiments, magnesium has been shown to be involved in several steps of the atherosclerotic process and, although in humans the situation is somewhat more complex, magnesium ions play an extremely important role in CHF and various cardiac arrhythmias. A number of drugs commonly used to treat CHF can significantly affect not only cellular magnesium ion homeostasis, but potassium as well. These include mercurial, thiazide, and loop diuretics. It has also been reported that hypomagnesemia is common in digitalis intoxication. In contrast, a number of agents have been shown to have either a magnesium conserving effect (potassium-sparing diuretics) or not to affect magnesium ion balance (angiotensin-converting enzyme inhibitors). The clinical consequences of magnesium deficiency include the development of various cardiac arrhythmias, all of which respond well to magnesium treatment. Thus, it is more than apparent that magnesium ion homeostasis is of major importance in CHF. Future studies should address the complex role of magnesium ions in electrolyte imbalance, particularly in relation to heart failure. PMID- 1414895 TI - Effect of angiotensin-converting enzyme inhibitors on the peripheral circulation in heart failure. AB - In patients with chronic heart failure, the increase in blood flow to working muscle is attenuated and oxygen consumption is lower for any given workload of exercise, compared with normal subjects. This impaired metabolic vasodilation during exercise cannot be restored with short-term administration of angiotensin converting enzyme (ACE) inhibitors. However, long-term ACE inhibition increases blood flow to skeletal muscle, and this increase is closely correlated with improvement in systemic oxygen consumption. The delayed effect of ACE inhibitors may be related to an interference with the vascular tissue renin-angiotensin system and remodeling of the vascular wall. In addition, endothelial-dependent dilation in response to acetylcholine is blunted in the forearm of patients with chronic heart failure, indicating an impaired endothelial function in this setting. There is experimental evidence that long-term ACE inhibition improves endothelial dysfunction; thus, one might speculate that the beneficial long-term effect of ACE inhibitors on peripheral flow may be, in part, related to its ability to restore normal endothelial function. Vasodilators such as hydralazine that improve blood flow to working muscle after acute administration do not increase skeletal muscle oxygen consumption, indicating that oxygen utilization is not improved. Ultrastructural analysis of skeletal muscle revealed that intrinsic alterations of skeletal muscle exist in patients with chronic heart failure; that is, the oxidative capacity of skeletal muscle is impaired in severe heart failure and contributes to the reduced exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414896 TI - Comparison of coronary responses to intracoronary and intraaortic ergonovine and isosorbide dinitrate in patients with atypical chest pain. AB - Fifty patients with atypical chest pain were studied to compare coronary responses to intracoronary and intraaortic ergonovine. The diameters of the proximal, middle (1) and (2) (proximal segments of segments 2 and 3 [AHA classification], respectively), and distal segments of the right coronary artery were measured before and after intracoronary ergonovine (4 micrograms/minute over 4 minutes) and isosorbide dinitrate (ISDN) (2 mg) in 24 patients, and before and after intraaortic ergonovine (0.2 mg) and ISDN (5 mg) in 26. Mean vasoconstriction by intracoronary and intraaortic ergonovine were 13 +/- 1.5% and 9 +/- 0.8%, respectively (p < 0.02). Irrespective of the methods of administration, the responses to ergonovine were similar in the 4 segments. Mean vasodilation by intracoronary and intraaortic ISDN, which were used to quantify the degree of basal coronary tone, were 25 +/- 2.2% and 27 +/- 1.5%, respectively (p = not significant [NS]). There were significant negative linear correlations between the responses to ergonovine and ISDN in the middle (2) (r = -0.51; p < 0.05) and distal (r = -0.53; p < 0.01) segments in patients with intracoronary injection, and the proximal (r = -0.41; p < 0.05), middle (1) (r = -0.66; p < 0.01) and middle (2) (r = -0.69; p < 0.01) segments in patients with intraaortic injection. These observations indicate that low-dose administration of intracoronary ergonovine produces sufficient coronary vasoconstriction, similar to or slightly greater than that of intraaortic ergonovine in patients with atypical chest pain, but basal coronary tone may influence the vasoreactivity to ergonovine. PMID- 1414897 TI - Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. The Liposorber Study Group. AB - A subgroup of patients with familial hypercholesterolemia (FH) respond inadequately to standard diet and drug therapy, and are therefore at high risk for the premature development or progression of coronary artery disease. This study evaluated low-density lipoprotein (LDL) cholesterol and lipoprotein (a) removal in a multicenter, controlled trial with a new LDL apheresis procedure (Liposorber LA-15 System). The study comprised patients with FH who had not responded adequately to diet and maximal drug therapy. There were 54 patients with heterozygous FH (45 randomized to treatment and 9 control subjects) and 10 with homozygous FH (all of whom received LDL apheresis). The study included three 6-week treatment phases and a 4-week rebound phase. Treatments were administered at 7- to 14-day intervals. Mean acute reductions in LDL cholesterol were 76% in heterozygous FH patients and 81% in homozygous ones. Time-averaged levels of LDL cholesterol were reduced 41% (243 to 143 mg/dl) in heterozygous FH patients and 53% (447 to 210 mg/dl) in homozygous ones. The substantial acute reduction of lipoprotein (a) (means: 65%, heterozygous FH; 68%, homozygous FH) has not been reported with other therapies. The Liposorber LA-15 System represents an important therapeutic option in FH patients who respond inadequately to diet and drug therapy. PMID- 1414898 TI - Measurement of ventricular electrogram amplitude during intraoperative induction of ventricular tachyarrhythmias. AB - Adequate sensing of ventricular tachycardia (VT) and ventricular fibrillation (VF) is necessary for proper functioning of an implantable cardioverter defibrillator (ICD). Several ICDs currently undergoing investigation have programmable fixed gain sensitivity for tachycardia detection. If intracardiac electrogram amplitude decreases below the programmed sensitivity during VT or VF, detection of a ventricular arrhythmia may be delayed or missed. The mean amplitude of intracardiac electrograms (ICEGM) recorded with bipolar epicardial or transvenous sensing leads was measured in 63 patients during induced VT and VF recorded in the operating room at the time of ICD implantation. The mean amplitude of the ICEGM during 41 episodes of VF in 15 patients decreased from 14.9 +/- 0.9 mV during sinus rhythm to 8.8 +/- 0.7 mV at 1 second, 9.7 +/- 0.7 mV at 5 seconds, and 9.4 +/- 0.7 mV at 10 seconds (p < 0.0001 vs sinus rhythm ICEGM) with endocardial leads. The mean amplitude of the ICEGM recorded during 173 episodes of VF in 43 patients with epicardial leads decreased from 10.4 +/- 0.3 mV in sinus rhythm to 7.8 +/- 0.3 mV at 1 second, 8.3 +/- 0.3 mV at 5 seconds and 8 mV at 10 seconds (p <0.0001 vs sinus rhythm ICEGM). The mean amplitude of epicardial and transvenous ICEGMs recorded during 34 episodes of monomorphic VT decreased from 18.5 +/- 1.8 mV (epicardial) and 14.4 +/- 2.0 mV (transvenous) during sinus rhythm (p = 0.15, epicardial vs transvenous) to 16.0 +/- 1.7 mV (epicardial) and 13.7 +/- 1.9 mV (transvenous) at 10 seconds (< 10% of baseline amplitude).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414899 TI - Effects of chronic amiodarone therapy on defibrillation threshold. AB - In a prospective and parallel, randomized study, the long-term stability of epicardial defibrillation threshold was evaluated in 22 patients, using a patch patch lead configuration at the time of implantation and generator replacement. The concomitant antiarrhythmic drug treatment consisted of either mexiletine (720 mg/day) or amiodarone (400 mg/day) and was administered to patients in a randomized and parallel manner. During a mean follow-up of 24 +/- 6 months, the defibrillation threshold increased significantly from 14.3 +/- 2.8 to 17.9 +/- 5.3 J (p < 0.05) for the entire patient group. The increase in the chronic defibrillation threshold was due to a marked increase in defibrillation energy needs in the subgroup of patients receiving amiodarone. Whereas no significant change in the defibrillation threshold was documented in the subgroup of patients receiving mexiletine, the mean defibrillation threshold increased from 14.1 +/- 3.0 to 20.9 +/- 5.4 J (p < 0.001) in those receiving amiodarone. In all patients with increased defibrillation thresholds, reevaluation showed a reduction in the defibrillation threshold after discontinuation of antiarrhythmic drug therapy. The only variable associated with an increase in the chronic defibrillation threshold was amiodarone treatment. These findings suggest that the defibrillation threshold should be measured at each generator replacement and in case of a change in antiarrhythmic drug treatment. In particular, if amiodarone treatment is initiated, it is recommended that the defibrillation threshold should be reevaluated to ensure an adequate margin of safety. PMID- 1414900 TI - Stress response pattern in obesity and systemic hypertension. AB - Under resting conditions obese hypertensive patients have been described as having a greater cardiac output and lower total peripheral resistance than lean hypertensive patients. To evaluate the hemodynamic patterns under stress conditions, we determined the hemodynamic response to mental stress (first study) and during isometric exercise (second study) in hypertensive patients with a body mass index > 27 kg/m2 (obese) and < 27 kg/m2 (lean). The cohort exposed to mental stress comprised 54 white male patients (30 were lean, 24 were obese) with untreated stage I or II essential hypertension according to the World Health Organization. Obese subjects responded with a higher increase in total peripheral resistance (p < 0.02) and lower increases in heart rate (p < 0.01), cardiac output (p < 0.01) and stroke volume (p < 0.02) when compared with their lean counterparts. This was independent of any differences in chemical or baseline hemodynamic characteristics at rest. The cohort exposed to isometric stress consisted of 57 patients (30 were lean, 27 were obese) with World Health Organization stage I or II essential hypertension. Obese subjects responded with exaggerated increases in systolic (p < 0.04) and diastolic (p < 0.01) pressures, and heart rate (p < 0.04) when compared with lean patients. Body mass index emerged as an independent determinant of the increase in systolic (r = 0.03) and diastolic (r = 0.01) pressure as well as of heart rate (r = 0.03). These results indicate that obese hypertensive patients respond to (1) mental stress with vasoconstriction instead of the expected vasodilation, and to (2) isometric stress with an exaggerated increase in arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414901 TI - Transesophageal echocardiographic monitoring of percutaneous mitral balloon valvulotomy. AB - This study was designed to evaluate the usefulness of performing transesophageal echocardiography (TEE) during percutaneous mitral balloon valvulotomy (PMBV). TEE was performed in 35 consecutive patients with symptomatic severe mitral stenosis during PMBV (group A). Another group of 27 patients with mitral stenosis who underwent PMBV without TEE was used for comparison (group B). TEE was most helpful in guiding transseptal puncture, aiding in proper positioning of the balloon during the dilatation procedure and enabling early detection of complications. The results show that PMBV when aided by TEE has a tendency to decrease the frequency of significant mitral regurgitation without compromising the final mitral valve area. TEE decreased the x-ray exposure time and was well tolerated. Thus, TEE provides information that makes this interventional catheterization procedure safer and easier to perform. PMID- 1414902 TI - Quantitative dynamics of left ventricular emptying and filling as a function of heart size and stroke volume in pure aortic regurgitation and in normal subjects. AB - Quantitative understanding of the dynamics of left ventricular (LV) emptying and filling as the left ventricle dilates but maintains ejection fraction is limited. Cine computed tomography was used to quantify peak LV emptying and filling characteristics in 30 patients with normal ejection fraction but variable end diastolic and stroke volumes. Group I consisted of 15 normal male patients and group II of 15 male patients with chronic, well-compensated, isolated aortic regurgitation. For each patient global LV volumes, absolute peak emptying and peak early diastolic filling rates and the timing of these maximal slopes were quantified. Mean arterial pressure and heart rate were within the normal range and ejection fraction and ages similar between groups I and II. Between-group analyses showed significantly increased end-diastolic and stroke volumes in group II compared with group I but nearly identical end-systolic volumes. Likewise, absolute peak emptying and filling rates were significantly greater in group II than in group I patients. The ratio of peak emptying rate to peak filling rate remained constant between groups. Timing of peak emptying and filling were similar in both groups. Absolute LV peak emptying and filling rates were found to vary linearly with end-diastolic and stroke volumes in all subjects examined. However, referencing peak emptying or peak filling rates to end-diastolic or total stroke volumes eliminated intergroup differences. Thus, in the presence of preserved ejection fraction and normal arterial pressure, the dynamic rates of LV emptying and early diastolic filling increase in direct proportion to absolute end-diastolic and stroke volumes, but the ratio of peak emptying to peak filling rate remains constant. PMID- 1414903 TI - Effects on platelet aggregation and fibrinolytic activity during upright posture and exercise in healthy men. AB - The circadian variation of acute myocardial infarction suggests that daily activities such as assuming the upright posture and performing different daily activities may trigger the onset of coronary thrombosis. Such triggering may result from unfavorable alterations in the balance between the prothrombotic and antithrombotic properties of the blood. The present study compares the effects of 2 common daily activities, assuming the upright posture and exercise, on platelet aggregation and fibrinolytic activity. In healthy male subjects, assuming the upright posture in the morning significantly increased platelet aggregation and produced only a moderate increase in fibrinolytic activity within 10 minutes. These changes were still present after 90 minutes in the upright posture. Supine posture for 45 minutes resulted in levels of fibrinolytic activity and platelet aggregation comparable to that observed before initially assuming the upright posture in the morning. Return to the supine posture for 45 minutes resulted in levels of fibrinolytic activity and platelet aggregation comparable to that observed before the initial assumption of upright posture. The changes recurred when upright posture was taken later in the day. Exercise did not increase platelet aggregation to levels beyond that produced by the upright posture, but was associated with a marked increase in fibrinolytic activity. Thus, exercise and upright posture produce distinctive alterations in the thrombogenic potential of the blood that may influence the timing of clinical vascular events. PMID- 1414904 TI - Transesophageal echocardiography to assess mitral valve function and flow during cardiopulmonary resuscitation. AB - This study further defines the mechanism of blood flow during closed-chest compression using transesophageal Doppler echocardiography. Although the echocardiographic demonstration of mitral valve closure during closed-chest compression has been used as evidence of direct cardiac compression, mitral valve closure has also been documented to occur during resuscitation by selectively increasing intrathoracic pressure. Transesophageal Doppler echocardiography was used to assess mitral valve position and flow in 17 adult patients undergoing cardiopulmonary resuscitation with a mechanical piston compression device. Left and right ventricular fractional shortening, mitral valve position with chest compression, timing and magnitude of transmitral flow, and anteroposterior chest diameter were recorded. In 12 patients (group I), the mitral valve closed during the down-stroke of chest compression; in the remaining 5 (group II), it opened further. Peak transmitral flow occurred during the release phase and was significantly higher (p < 0.05) in group I (39.5 +/- 9.3 cm/s) than the peak flow in group II (21.3 +/- 5.9 cm/s), which occurred during the downstroke of chest compression. Left ventricular fractional shortening inversely correlated (r = 0.68; p = 0.02) with the anteroposterior chest diameter, but did not correlate with peak transmitral flow (r = 0.34; p = not significant). It is concluded that the mitral valve closes during the downstroke of chest compression in most adult patients during resuscitation. The absence of a relation between mitral valve flow and left ventricular fractional shortening supports the hypothesis that other factors such as nonuniform increases in intrathoracic pressure cause the mitral valve to open or close during chest compression. PMID- 1414905 TI - A new technique for simultaneous monitoring of electrocardiogram and walking cadence. AB - A new technique for simultaneously recording continuous electrocardiographic (ECG) data and walking step rate (cadence) is described. The ECG and gait signals are recorded on 2 channels of an ambulatory Holter monitor. Footfall is detected using ultrathin, force-sensitive foot switches and is frequency modulated. The footfall signal provides an indication of the subject's activity (walking or standing), as well as the instantaneous walking rate. Twenty-three young and elderly subjects were studied to demonstrate the use of this ECG and gait recorder. High-quality gait signals were obtained in all subjects, and the effects of walking on the electrocardiogram were assessed. Initial investigation revealed the following findings: (1) Although walking rates were similar in young and elderly subjects, the elderly had both decreased heart rate (HR) variability (p < 0.005) and increased cadence variability (p < 0.0001). (2) Overall, there was an inverse relation between HR and cadence variability (r = -0.73). Three elderly subjects with no known cardiac disease had HR and cadence variability similar to those of the young, whereas elderly subjects with history of congestive heart failure were among those with the lowest HR variability and the highest cadence variability. (3) Low-frequency (approximately equal to 0.1 Hz) HR oscillations (frequently observed during standing) persisted during walking in all young subjects. (4) In some subjects, both step rate and HR oscillated at the same low frequency (approximately equal to 0.1 Hz) previously identified with autonomic control of the baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414906 TI - Impact of food on the pharmacokinetics and electrocardiographic effects of sustained release verapamil in normal subjects. AB - To evaluate the impact of food on the pharmacokinetics and electrocardiographic effects of sustained release (SR) verapamil tablets, 9 healthy men each received 3 single doses of verapamil in a randomized, crossover manner: 10 mg of intravenous verapamil, 240 mg SR verapamil on an empty stomach, and 240 mg SR verapamil with a standardized meal. PR intervals and racemic verapamil serum concentrations were measured serially over 30 hours after administration. The time to peak concentration was longer (7.5 +/- 3.0 vs 4.4 +/- 2.3 hours), resulting in a lower peak verapamil serum concentration (118 +/- 43 vs 175 +/- 50 ng/ml) when SR verapamil was administered with food (p < 0.05). Food tended to decrease the bioavailability of SR verapamil (34 +/- 12 vs 49 +/- 14%), although this difference did not reach statistical significance (p = 0.065). Precipitous or exaggerated release of verapamil from the SR tablet was not observed in any subject during the fasting state. Prolongation of the PR interval paralleled these alterations in serum concentration. The maximal change in the PR interval was greater (21 +/- 8 vs 14 +/- 5%; p < 0.05) when SR verapamil was given in the fasting state. Although an exaggerated verapamil release or effect was not observed, food significantly altered the absorption and electrocardiographic effects of a single dose of SR verapamil. Manipulation of the administration condition may be helpful in achieving desired outcomes. PMID- 1414907 TI - Differences in men and women in coronary artery disease, systemic hypertension and their treatment. AB - Various studies have shown that women with coronary artery diseases are treated quite differently from men, although the reasons for these differences are not easily discernible and may be based on misconceptions. Furthermore, although the attributable risk percentage for cardiovascular complications of hypertension is higher in women than in men, little information on treating hypertension in women is available. There is cause for concern owing to some findings that white women may be harmed by antihypertensive treatment unless that treatment differs from that of men. Consensus on the importance of this finding has not been reached. PMID- 1414908 TI - Left ventricular shape abnormalities in inferior wall myocardial infarction. PMID- 1414909 TI - Coronary angiography with four French catheters. PMID- 1414910 TI - Usefulness of total 12-lead QRS voltage in diagnosing left ventricular hypertrophy in clinically isolated, pure, chronic, severe mitral regurgitation. PMID- 1414911 TI - Postpartum cardiomyopathy associated with maternal cocaine abuse. PMID- 1414912 TI - Left ventricular Doppler inflow signals in children with isolated ventricular septal defect. PMID- 1414913 TI - Electrocardiographic and echocardiographic features of left atrial size after orthotopic cardiac transplantation. PMID- 1414914 TI - Echocardiographic determinants of clinical outcome in subjects with coronary artery disease (the Framingham Heart Study). AB - Echocardiographic predictors of clinical outcome were examined in subjects from the Framingham Heart Study with overt coronary artery disease. The study population consisted of 185 men and 147 women with coronary artery disease who underwent M-mode echocardiography and were followed for a mean of 3.90 years. At baseline, 37 men (18.4%) and 16 women (10.9%) had reduced fractional shortening, 43 men (23.2%) and 28 women (19%) had left ventricular (LV) dilatation, and 76 men (41%) and 76 women (51.7%) had LV hypertrophy. During the follow-up period new cardiovascular disease events (coronary disease, stroke, transient ischemic attack, claudication, heart failure and deaths from cardiovascular disease) occurred in 60 men (32%) and 58 women (39%). With use of age-adjusted proportional hazards analyses, LV mass/height in men (relative risk [RR] = 1.25/50 g/m increment, 95% confidence interval [CI] 1.01 to 1.55) and LV end diastolic diameter in women (RR = 1.36/5 mm increment, 95% CI 1.05 to 1.76) were predictors of new cardiovascular disease events. Cardiovascular risk was also associated with LV end-systolic diameter in both sexes (in men RR = 1.28/1 SD increment, 95% CI 1.02 to 1.63; in women RR = 1.40/1 standard deviation increment, 95% CI 1.09 to 1.82). Reduced fractional shortening alone (RR = 1.91, 95% CI 1.11 to 3.31) and in combination with LV dilatation (RR = 2.13, 95% CI 1.13 to 4.02) was associated with the incidence of new cardiovascular disease outcomes in men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414915 TI - Risk factor correlates of coronary calcium as evaluated by ultrafast computed tomography. AB - Coronary artery calcium is invariably associated with atherosclerosis and has been linked to an increased risk of coronary events. Ultrafast computed tomography (CT) was recently used to document the presence and relative quantity of coronary calcium. The use of the self-reported coronary risk factors to identify persons with coronary calcium as documented by ultrafast CT screening was examined in 458 men and 139 women aged 26 to 81 years (88% asymptomatic). All subjects underwent ultrafast CT scanning, and received a questionnaire and underwent an interview regarding medical and risk factor history. Total calcium score was calculated as the sum of lesion-specific scores, each calculated as the product of density > or = 130 Hounsfield units and area > or = 0.51 mm2. The prevalence of coronary calcium increased significantly (p < 0.01) by age group, and the greater the number of risk factors present, the greater the likelihood of calcium. From multiple logistic regression, age (p < 0.01), male sex (relative risk [RR] 3.03; p < 0.01), and history of smoking (RR 1.85; p < 0.01) and hypertension (RR 1.65; p < 0.05) were independently associated with the probability of detectable calcium. Among asymptomatic subjects, an association with hypercholesterolemia was also seen (RR 1.56; p < 0.05). The results demonstrate that cardiovascular risk factors can help in identifying the likelihood of coronary calcium. PMID- 1414916 TI - Circulating aggregated platelets, number of platelets per aggregate, and platelet size during acute myocardial infarction. AB - Circulating aggregated platelets (total, reversibly and irreversibly aggregated), the number of platelets per aggregate and "big" platelets were measured by a modification of the Wu and Hoak method in 42 patients on the first, second and fifth day of acute myocardial infarction (AMI). Among them, 30 had an uncomplicated course and 12 patients had complications that occurred between the 5th and 10th day of hospitalization (7 patients had reinfarction and 5 died). In all patients the measured parameters were elevated compared with those of control subjects. There was a significant increase, especially after the first observation day, in the values of total aggregated platelets (37 +/- 11% vs 26 +/ 12%, p < 0.001), reversibly aggregated platelets (27 +/- 9% vs 17 +/- 8%, p < 0.001) and the average platelets per aggregate (8.6 +/- 0.3 vs. 2.3 +/- 0.4) in patients with versus without complications. In considering the role of platelets in the development of AMI, these findings may add information to the role of platelets in determining the course of AMI. PMID- 1414917 TI - Effects of simulated left bundle branch block on QRST time-integral values of 12 lead electrocardiograms in patients with and without prior anterior wall myocardial infarction. AB - The effects of right ventricular pacing, which simulated left bundle branch block (BBB), on QRST time-integral values of 12-lead electrocardiograms (ECGs) were examined, and the clinical usefulness of QRST values for estimating the severity of left ventricular wall motion abnormalities due to a prior anterior wall myocardial infarction (MI) in the setting of left BBB were evaluated. Digitized ECGs were recorded during normal sinus rhythm and simulated left BBB in 38 patients (24 with and 14 without prior anterior wall MI). QRST values were calculated in each lead point of 12-lead ECGs. Data from 608 normal subjects were used as control values; the mean +/- 2 SD of these values was regarded as the normal range. The parameter sigma DE was defined as the sum of the differences between the normal mean QRST value and the QRST values of a given patient in leads where the QRST value was less than the normal range. The correlation coefficient of sigma DE for the 2 activation sequences was highly significant. Although small but significant changes were seen in QRST values in leads I, II, III, aVR, aVF and V1 during simulated left BBB, left precordial leads showed no significant changes in QRST values. A criterion of sigma DE > 40 mV.ms for detecting an anterior wall MI showed a sensitivity of 88%, a specificity of 93%, and a diagnostic accuracy of 89%. The sigma DE was significantly (p < 0.001) correlated with the asynergy index calculated from left ventriculograms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414918 TI - Acute hemodynamic and electrophysiologic effects and safety of high-dose intravenous diltiazem in patients receiving metoprolol. AB - The anti-ischemic efficacy of diltiazem may improve with increments in dosage and with additional beta-blocking therapy. However, the combined administration could lead to adverse effects through amplification of negative inotropic and chronotropic properties. To evaluate hemodynamic tolerability and safety of high dose intravenous diltiazem in patients with coronary artery disease receiving long-term metoprolol treatment, 9 such patients were studied for 30 minutes after onset of intravenous diltiazem administration (0.5 mg/kg for 5 minutes, followed by 15 mg/hour). Diltiazem plasma levels peaked at 5 minutes (641 +/- 74 micrograms/liter), decreasing to 177 micrograms/liter at 30 minutes. Average metoprolol levels (43 +/- 12 micrograms/liter) did not change. Diltiazem immediately decreased systemic vascular resistance, left ventricular systolic and mean aortic pressures (29, 21 and 20%, respectively, at 5 minutes), and they remained significantly reduced at 30 minutes. Heart rate initially increased by 11% during the bolus infusion (p < 0.05). Concomitantly, contractility indexes Vmax and Vce40, measured at fixed heart rates, also increased significantly by 11%. Both heart rate and contractility indexes returned to baseline levels thereafter. Cardiac output increased by 10% (p = not significant), stroke index remained unchanged, but stroke work decreased significantly by 20%. Also, the tension-time index was significantly reduced (23%). Diltiazem induced moderate negative lusitropic effects, the first derivative of negative left ventricular pressure decline decreased by 12% and Tau 2 lengthened by 13%. Concomitantly, left ventricular filling pressure increased from 19 +/- 2 to 23 +/- 3 mm Hg, but only at 5 and 15 minutes. PQ, QRS and QTc intervals were not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414919 TI - A symposium: systemic hypertension: contribution of trandolapril, a new angiotensin-converting enzyme inhibitor, toward patient protection. Introduction. PMID- 1414920 TI - Can the genetic factors influence the treatment of systemic hypertension? The case of the renin-angiotensin-aldosterone system. AB - The hereditary nature of familial hypertension has been clearly established by a number of clinical studies. About 30% of the blood pressure variance can be attributed to genetic factors. As a consequence, the relative risk for developing coronary artery disease or cardiovascular death is increased in patients with a family history of hypertension and cardiovascular disease. Patients with such familial history should be considered at the same risk as those who have independent epidemiologic risk factors. The development of molecular genetics allows establishment of a link between high blood pressure, intermediate phenotypes, and the genes involved in blood pressure regulation. Gene markers should be available in the near future that will help to identify patients predisposed to hypertension. The genes of the renin-angiotensin-aldosterone system are good examples of candidate genes whose products are known to participate in blood pressure regulation. The possible involvement of these genes in essential hypertension is critically analyzed. PMID- 1414921 TI - Prevention of myocardial infarction. AB - Despite substantial progress in cardiovascular disease prevention, stroke and myocardial infarction remain the leading causes of death throughout the industrialized world. Treatment of high blood pressure, while contributing importantly to this progress, remains inefficient and less than optimally effective, particularly in regard to coronary artery disease events. Therapeutic intervention in the renin-angiotensin system offers promise of progress on both these fronts. Renin-sodium profiles have been shown to permit prognostic stratification of otherwise indistinguishable hypertensive patients. Indeed, low renin subjects, without other cardiovascular risk factors, have a particularly favorable prognosis. Now, the pharmacologic ability to mute the pathologic effects of angiotensin II also offers the genuine possibility that the cardioprotective value of antihypertensive therapy may be significantly improved. PMID- 1414922 TI - Trandolapril in hypertension: overview of a new angiotensin-converting enzyme inhibitor. AB - Trandolapril is a new angiotensin-converting enzyme (ACE) inhibitor that has been extensively investigated in vitro, in animals, in normal volunteers, and in hypertensive patients. It has been shown to exert all the effects typical for the class of ACE inhibitors, and has a marked impact on the reversal of structural hypertrophy of the myocardium and the arterial wall. Trandolapril is a prodrug that must be hydrolyzed to its active metabolite, trandolaprilat. This latter compound exhibits a particularly high affinity for converting enzyme, which results in a slow dissociation and one of the longest durations of action of any converting enzyme inhibitor known so far. Trandolapril reduces blood pressure consistently throughout the 24-hour period following intake. Accordingly, trandolapril, more than any other drug of its class, can be considered a true, once-a-day antihypertensive drug. PMID- 1414923 TI - Effects of trandolapril on vascular morphology and function during the established phase of systemic hypertension in the spontaneously hypertensive rat. AB - The aim of this study was to determine the morphologic and functional vascular changes occurring following 4 weeks of treatment with the angiotensin-converting enzyme inhibitor trandolapril in the spontaneously hypertensive rat (SHR) in the established phase of hypertension. At the dosage used, 0.4 mg/kg orally, trandolapril decreased blood pressure of the SHR by 15-18% compared with that of the control animals. Immediately before the end of treatment, the following changes from control values were observed: (1) 9, 11, and 12% reductions for myocardial hypertrophy and the media thickness of the thoracic aorta and femoral arteries, respectively; and (2) an increase in the compliance of the resistance arteries, demonstrated by a shift to the right of the in vitro tension-diameter curves and a significant 22% increase in their normalized internal diameter, while their maximum contractile ability was significantly decreased. Following discontinuation of treatment, blood pressure levels remained significantly lower in the treated versus the control groups for up to 4 weeks after the last administration. At that time measurement of the studied parameters showed: (1) a rapid reversion to control values of the compliance of the resistance vessels; and (2) a slower progression, but in the same direction, in the parameters of cardiac and vascular hypertrophy. Thus, trandolapril, administered for a short period in the adult SHR, was able to reverse the cardiac and vascular morphologic changes present in this model of hypertension. Like the effect on blood pressure, these effects were slowly reversible at the end of treatment, whereas the functional consequences at the resistance artery level seemed to display a more rapid reversibility. PMID- 1414924 TI - Clinical value of blood pressure measurements: focus on ambulatory blood pressures. AB - Because clinic blood pressure values are compromised by 2 major limitations--the alerting reaction to clinic measurements and the spontaneous blood pressure variability--they have only a limited correlation with average 24-hour blood pressure values. Whether the latter should be employed routinely in substitution for, or in addition to, traditional blood pressure measurements has not yet been determined, however. To date, average 24-hour blood pressure values have been shown to correlate more closely than clinic blood pressure values with the organ damage of hypertension. A correlation with organ damage has been shown also for a number of blood pressure values within the 24 hours. Nevertheless, the clinical importance of 24-hour blood pressure and blood pressure variability has never been confirmed by prospective controlled studies. This information needs to be obtained before this approach is routinely employed in the clinical practice. PMID- 1414925 TI - Beneficial effects of trandolapril on experimentally induced congestive heart failure in rats. AB - Angiotensin-converting enzyme (ACE) inhibitors have been shown to prolong life expectancy in patients with congestive heart failure. In order to determine the relative contributions of the different factors involved in this beneficial effect, we investigated in an experimental model of postinfarction cardiac insufficiency in the rat over a 9-12-month period (1) the kinetics of the development of the hemodynamic, biologic, and morphologic alterations that accompany heart failure, and (2) the kinetics of the effects of a new, long acting ACE inhibitor, trandolapril. Following induction of infarction, systolic blood pressure, left ventricular dP/dt, and end-diastolic pressure were immediately decreased, decreased, and increased, respectively, and these modifications persisted throughout the study. Cardiac index, on the other hand, was only initially and transiently decreased. Cardiac remodeling (left ventricular dilation, myocardial hypertrophy, and fibrosis) occurred as early as 7 days after infarction and worsened throughout the study. Plasma atrial natriuretic factor (ANF) and urinary cyclic guanosine monophosphate (cGMP) were also increased. In this model, a 1-year oral treatment with trandolapril resulted in early hemodynamic and biologic beneficial effects (reductions in pre- and afterload, increase in cardiac index, and decrease in plasma ANF), and in a delayed reversal of the infarction-induced cardiac morphologic alterations. Hence, the trandolapril-induced increase in survival rate is due initially to the drug's hemodynamic effects and over the long-term to both its hemodynamic and cardiac morphologic (limitation of remodeling) effects. PMID- 1414926 TI - Reversal of cardiac and large artery structural abnormalities induced by long term antihypertensive treatment with trandolapril. AB - In 15 patients with untreated mild to moderate essential hypertension and left ventricular hypertrophy, we assessed blood pressure, echocardiographic left ventricular mass index, brachial artery compliance (pulsed doppler flowmetry), and calculated forearm vascular resistance (strain gauge plethysmography) before, during (6 and 12 months) and after (1 month washout period) 1 year of satisfactory (blood pressure < or = 140/90 mm Hg) antihypertensive therapy with the angiotensin-converting enzyme inhibitor trandolapril (2.0 mg orally once daily). During the antihypertensive effective treatment, we observed a significant reduction of systolic and diastolic blood pressures, left ventricular mass index, and forearm vascular resistance at both 6 and 12 months. In addition, brachial artery compliance was significantly increased. After washout, systolic (156 +/- 3 mm Hg) and diastolic (102 +/- 1 mm Hg) blood pressures returned to levels comparable to baseline. However, left ventricular mass index (132 +/- 4; p < 0.01) and brachial artery compliance (1.53 +/- 0.01; p < 0.01) were still different from baseline. These results demonstrate that chronic antihypertensive treatment with trandolapril is associated with a stable regression of cardiac and vascular abnormalities, which is partially unrelated to the blood pressure lowering effect. PMID- 1414927 TI - Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group. AB - The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension. After a washout period of 4 weeks, 42 patients were randomized to receive 2 mg of trandolapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks. This was followed by a second washout period of 4 weeks. At the end of each period, clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively, taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night. Two patients were dropped out before any blood pressure evaluation under treatment. Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data (2 values per hour during the day and 1 value per hour in the night). In the trandolapril-treated group (n = 41) clinic systolic/diastolic blood pressures were 159.8 +/- 2.0/102.4 +/- 0.8, 146.8 +/- 2.3/94.8 +/- 1.1, and 155.7 +/- 2.0/99.2 +/- 0.7 mm Hg in the pretreatment, treatment, and post-treatment periods, respectively. The corresponding values for 24-hour mean blood pressure (n = 31) were 139.5 +/- 1.9/91.2 +/- 1.5, 131.0 +/- 2.0/84.3 +/- 1.2, and 139.7 +/- 1.8/90.9 +/- 1.1 mmHg. The differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414928 TI - After the diagnosis of systemic hypertension, is risk factor management important? AB - In the hypertensive patient, the presence of other cardiovascular risk factors, particularly smoking, hypercholesterolemia, obesity, and diabetes, greatly influences the prognosis. In many patients, these other risk factors are linked, perhaps by adverse effects of pressure on endothelial function. The newer antihypertensive agents may have better effects on prognosis by ameliorating these other risk factors, as well as lowering pressure. We await trials to see if this promise is fulfilled. PMID- 1414929 TI - Influence of vessel selection on the observed restenosis rate after endoluminal stenting or directional atherectomy. AB - In comparing the restenosis rates among different interventions, 1 potential confounder might be the differences in the vessels treated, as dictated by the technical limitations of particular devices. The purpose of this study was to use current "acute gain-late loss" analysis to examine what influence vessel selection has on the restenosis rates seen after coronary stenting or directional atherectomy. The minimal luminal diameter of native coronary lesions was measured before and immediately after intervention in 102 single Palmaz-Schatz stents and 347 atherectomies, 367 (82%) of which had repeat angiographic measurement 6 months after intervention. Atherectomy-treated lesions had a higher proportion of left anterior descending to right coronary arteries (68 vs 24%) compared with stents (31 vs 54%), p < 0.001. Although subsequent restenosis rates were similar for stenting (25%) and atherectomy (30%, p = 0.42), left anterior descending versus right coronary lesions had a significantly higher restenosis rate for the overall group (35 vs 18%, p = 0.009), for stents (44 vs 13%, p = 0.008) and for atherectomy (35 vs 22%, p = 0.10), respectively. Multivariable analysis demonstrated that postprocedure luminal diameter (p = 0.03, p = 0.009) and coronary location (the proportion of left anterior descending vessels treated, p = 0.002, p < 0.001), but not device type (stent vs atherectomy), were strong independent determinants of restenosis according to both binary (> 50% diameter stenosis) and continuous (late percent stenosis) definitions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414930 TI - Detection of silent coronary artery disease in adolescents and young adults with familial hypercholesterolemia by single-photon emission computed tomography thallium-201 scanning. AB - Familial hypercholesterolemia (FH), a genetic disease characterized by increased levels of total and low-density lipoprotein cholesterol in the blood, results in a markedly increased incidence of atherosclerosis and coronary artery disease in homozygotes and to a lesser extent in heterozygotes. The purpose of this study was to detect the presence of myocardial ischemia, particularly in heterozygotes, with stress single-photon emission computed tomography thallium-201 scanning and to determine if there were any differentiating variables between heterozygotes with normal and abnormal thallium-201 scans. Fifty-four patients (mean age 16 years; range 8 to 24) with FH were analyzed (4 homozygotes and 50 heterozygotes). Eleven heterozygotes and 3 homozygotes had abnormal thallium-201 scans. Family history, lipid profile, age and sex of heterozygotes with FH did not predict the presence of myocardial ischemia. The mean total cholesterol level in heterozygotes with normal thallium-201 scans was 7.68 +/- 2.29 mmol/liter (297 mg/dl), which was not significantly different from that in heterozygotes with abnormal scans (7.63 +/- 1.07 mmol/liter [295 mg/dl]; p = 0.91). The coronary angiography of 1 homozygote who had an abnormal thallium-201 scan demonstrated a 50% stenosis of the left anterior descending artery. Aggressive, repetitive plasma exchange was then instituted. The 11 heterozygotes with abnormal thallium 201 scans underwent more rigorous dietary and drug therapy. It is concluded that myocardial ischemia with stress in heterozygotes with FH can occur at a young age and that thallium-201 scanning should be performed early as a screening test and to guide patient management. PMID- 1414931 TI - Changing circadian variation of transient myocardial ischemia during the first year after a first acute myocardial infarction. AB - In a consecutive series of 123 men (aged 55 +/- 8 years) with a recent first acute myocardial infarction (AMI), 24-hour ambulatory ST-segment monitoring was performed early after discharge (day 11 +/- 5), 6 months (day 185 +/- 6) and 1 year (day 368 +/- 8) after AMI. No difference in the prevalence of transient myocardial ischemia was found between the 3 recordings (17, 17 and 20%), and most ischemic episodes were silent (98, 100 and 97%). In the early postinfarction period, a peak of ischemic activity was demonstrated between 6 P.M. and midnight (40 of 93 episodes [43%]). Over time, the maximal occurrence of ischemia gradually advanced toward the morning hours with a peak activity between 6 A.M. and noon at 1-year follow-up (32 of 73 episodes [44%]). Significantly more patients (16 of 21 [76%]) had ischemia from 6 P.M. to midnight at discharge compared with the findings 1 year later (9 of 23 patients [39%]) (p < 0.03). An opposite trend was found regarding patients who exhibited ischemic episodes in the hours from 6 A.M. to noon: 10 of 21 patients (48%) early after discharge versus 17 of 23 patients (74%) at 1-year follow-up (p = not significant). Results from the 6-month recording displayed characteristics between the findings from discharge and 1-year ambulatory monitoring. The pathophysiologic processes underlying the observations from this study are unknown. The change in circadian periodicity could not be explained from differences in heart rate variation patterns or medical antianginal treatment among the 3 recordings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414932 TI - Usefulness of heavy isometric exercise echocardiography for assessing left ventricular wall motion patterns late (> or = 6 months) after acute myocardial infarction. AB - The aim of this prospective study was to determine the effects of heavy isometric exercise on left ventricular (LV) wall motion patterns in patients who have had myocardial infarction, and to compare heavy isometric exercise with dynamic exercise for competence in eliciting LV wall motion abnormalities at equivalent rate-pressure products. Echocardiography was performed in 42 patients during supine bicycle ergometry and during heavy dynamometer stretching at 50% of maximal voluntary contraction. Systemic vascular resistance increased from 1,484 to 1,649 dynes s cm-5 (p < 0.05) during isometric exercise, and decreased significantly during dynamic exercise. Wall motion abnormalities or new asynergy were induced by isometric exercise in 120 segments, 107 of which (89%) showed significant stenosis of the perfusing coronary artery. Hypokinesia was the dominant pattern in the range of 76 to 90% narrowing; akinesia was dominant at 91 to 100% narrowing. Wall motion abnormalities were also documented in 13 segments (11%) assumed to be supplied by vessels with nonsignificant stenosis. Dyskinesia, seen in 7% of the segments, was equally distributed between both groups with significant stenosis. Sensitivity and positive predictive value in identifying specific coronary vessel disease was similar for both isometric and dynamic exercise. In conclusion, heavy isometric exercise in patients who have had myocardial infarction induces wall motion abnormalities of a severity proportional to the degree of coronary narrowing. This exercise method is similar to dynamic exercise for ability in identifying obstructions in a specific vessel. Furthermore, when compared at near-equal rate-pressure products, heavy isometric exercise is far superior in sensitivity to dynamic exercise. PMID- 1414933 TI - Patterns of myoglobin and MM creatine kinase isoforms release early after intravenous thrombolysis or direct percutaneous transluminal coronary angioplasty for acute myocardial infarction, and implications for the early noninvasive diagnosis of reperfusion. AB - Early noninvasive detection of reperfusion after thrombolysis for acute myocardial infarction may enable detection of unsuccessful thrombolysis in time for rescue percutaneous transluminal coronary angioplasty (PTCA). It has been suggested that repeated measurement of myoglobin or of MM creatine kinase (CK) isoforms enables early detection of reperfusion. Twenty consecutive patients with acute myocardial infarction treated by intravenous thrombolysis underwent serial determination of myoglobin, MM3 and MM1 CK isoforms every 30 minutes after the beginning of thrombolysis. At 90 minutes, coronary angiography was performed, enabling classification of patients as with (group A) and without (group B) reperfusion. A third group of 7 patients (group C) underwent direct PTCA without antecedent thrombolysis. In all groups, there were increases in myoglobin, percentage of MM3 isoform, and ratio of MM3/MM1. These increases appeared on the average steeper and faster in group B, but the large dispersion of values in this group resulted in a wide overlap with group A. Retrospective analysis suggests that an increase in the MM3/MM1 ratio > 0.35 after 60 minutes is very specific for reperfusion (sensitivity 60% and specificity 100%). In group C, PTCA always led to a sharp increase in all biochemical parameters measured within 30 minutes. Thus, macromolecular markers can be used for very early, noninvasive detection of reperfusion with a high specificity. This could help reduce the need for emergency angiography to select candidates for rescue PTCA. Furthermore, the patterns of biochemical markers of reperfusion differ when reperfusion is initiated by either thrombolysis or PTCA. PMID- 1414934 TI - Relation of body fat distribution in men and degree of coronary narrowings in coronary artery disease. AB - This study evaluates the relation between body fat distribution and severity of coronary artery disease (CAD). The study sample comprised 33 patients with angiographically demonstrated CAD and 10 angiographically normal control subjects. Body fat distribution was estimated by computed tomography and degree of coronary narrowings by angiographic score. Body weight, body mass index and total and subcutaneous abdominal adipose tissue areas showed no statistical differences in the 2 groups; visceral abdominal adipose tissue area and the visceral to subcutaneous abdominal adipose tissue area ratio were significantly higher in patients with CAD (p < 0.05). There was a significant correlation between visceral fat and triglycerides, apoprotein B and sum of glucose and insulin during glucose oral tolerance test. Sum of insulin during glucose oral tolerance test, visceral abdominal adipose tissue area and visceral/subcutaneous abdominal adipose tissue area ratio correlated significantly with severity of CAD, as evaluated by coronary score in all subjects and in CAD patients alone. Stepwise multiple regression analysis using the coronary score as the dependent variable and anthropometric and metabolic parameters as independent variables shows that in all subjects and in CAD patients alone, visceral/subcutaneous abdominal adipose-tissue area ratio entered the regression first and the sum of insulin during glucose oral tolerance test second. The results suggest that visceral abdominal adipose tissue area and visceral to subcutaneous abdominal adipose tissue area ratio may be cardiovascular risk factors. PMID- 1414935 TI - Beat-to-beat morphologic variability of the electrocardiogram for the evaluation of chest pain in the emergency room. AB - The value of electrocardiographic, morphologic variability in the early diagnosis of acute myocardial infarction (AMI) and myocardial ischemia was evaluated in 49 nonselected patients presenting to the emergency room with chest pain. High resolution electrocardiography was used to determine the morphologic variability of consecutive electrocardiographic complexes, and the ratio of the variance of the QRS onset to that of the entire electrocardiogram was calculated. A final diagnosis of AMI was confirmed in 8 patients, acute coronary insufficiency in 8, angina pectoris in 19, and a noncardiac origin for chest pain in 14. Patients with AMI had a significantly higher beat-to-beat electrocardiographic morphologic variability of the QRS onset (1.4 +/- 0.2) than did those with acute coronary insufficiency (1.1 +/- 0.2), angina pectoris (0.9 +/- 0.1) or noncardiac chest pain (0.8 +/- 0.1) (p < 0.05). The sensitivity of the clinical presentation, typical electrocardiographic changes and creatine phosphokinase levels for the diagnosis of an acute ischemic event on admission to the emergency room was 62, 25 and 37.5%, respectively. Relative variance of the QRS onset of > 0.86 had a sensitivity of 75% and a specificity of 61% for diagnosing an acute ischemic event. Logistic regression of these variables showed that the QRS onset relative variability is an independent predictor for an acute ischemic event. It is concluded that an increased beat-to-beat electrocardiographic variability in patients with AMI is present on admission to the emergency room and may assist in establishing the diagnosis in this setting. PMID- 1414936 TI - Degrees of coronary arterial narrowing at necropsy in men with large fusiform abdominal aortic aneurysm. AB - In 27 patients (mean age at death 72 +/- 9 years) with abdominal aortic aneurysm (AAA) > or = 5.0 cm in its widest transverse diameter, the amounts of narrowing at necropsy in the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries were determined. During life, 12 of the 27 patients (44%) had symptoms of myocardial ischemia: angina pectoris alone in 2, acute myocardial infarction alone in 3, angina pectoris and acute myocardial infarction in 5, and sudden coronary death in 2. Ten of the 27 patients (37%) died from consequences of myocardial ischemia. Six (22%) died from rupture of the AAA. Grossly visible left ventricular necrosis or fibrosis, or both, was present in 15 patients (56%). Of the 27 patients, 23 (85%) had narrowing 76 to 100% in cross-sectional area of 1 or more major coronary arteries by atherosclerotic plaque. The mean number of coronary arteries per patient severely (> 75%) narrowed was 2.0 +/- 1.3/4.0. Of the 108 major coronary arteries in the 27 patients, 55 (51%) were narrowed > 75% in cross-sectional area by plaque. The 4 major coronary arteries in the 27 patients were divided into 5-mm segments and a histologic section, stained by the Movat method, was prepared from each segment. The mean percentages of the resulting 1,475 five-mm segments narrowed in cross sectional area 0 to 25%, 26 to 50%, 51 to 75%, 76 to 95% and 96 to 100% were 17, 37, 28, 15 and 3%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414937 TI - Amounts of coronary arterial narrowing by atherosclerotic plaque at necropsy in patients with lower extremity amputation. AB - In 26 patients (mean age at death 68 +/- 9 years) who had undergone amputation (at mean age 63 +/- 12 years) of 1 or both lower extremities due to severe peripheral arterial atherosclerosis, the amounts of narrowing at necropsy in the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries were determined. During life, 15 of the 26 patients (58%) had symptoms of myocardial ischemia: angina pectoris alone in 1, acute myocardial infarction alone in 5, and angina and/or infarction plus congestive heart failure or sudden coronary death in 9. Twelve of the 26 patients (42%) died from consequences of myocardial ischemia: acute myocardial infarction in 5, sudden coronary death in 3, chronic congestive heart failure in 3, and shortly after coronary bypass surgery in 1. Grossly visible left ventricular necrosis or fibrosis, or both, was present in 21 patients (81%). Of the 26 patients, 24 (92%) had narrowing 76 to 100% in cross-sectional area of 1 or more major coronary arteries by atherosclerotic plaque. The mean number of coronary arteries per patient severely (> 75%) narrowed was 2.3 +/- 1.0/4.0. Of the 104 major coronary arteries in the 26 patients, 60 (58%) were narrowed > 75% in cross-sectional area by plaque. The 4 major coronary arteries in the 26 patients were divided into 5 mm segments and a histologic section, stained by the Movat method, was prepared from each segment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1414938 TI - Morphologic characterization and quantitative assessment of mitral regurgitation with ruptured chordae tendineae by transesophageal echocardiography. AB - To compare the accuracy of transesophageal echocardiography (TEE) with that of transthoracic echocardiography (TTE) in the detection of morphologic characteristics and in the quantitative assessment of the severity of mitral regurgitation with ruptured chordae tendineae, 40 patients with ruptured chordae tendineae (group 1) and 20 patients with moderate or severe mitral regurgitation due to other causes (group 2) were studied. All echocardiograms were recorded before cardiac surgery. Cardiac catheterization was performed in 55 patients (92%). TEE showed greater sensitivity and negative predictive value than TTE (100 vs 65%, and 100 vs 56%, respectively; p < 0.005) in the diagnosis of ruptured chordae tendineae. Visualization of the ruptured chordae (termed snake-tongue sign) was highly sensitive and specific (93 and 95%, respectively) for establishing the diagnosis of ruptured chordae tendineae. The severity of mitral regurgitation in group 1 patients evaluated by TTE color flow mapping was underestimated by 2 grades in 1 patient and by 1 grade in 6 patients, and overestimated by 1 grade in 1 patient, compared with left ventriculography. In contrast, by TEE color flow mapping it was underestimated by 1 grade in 1 and overestimated by 1 grade in 1 patient. TEE color flow mapping showed better correlation with angiography than did TTE color flow mapping (r = 0.82 vs r = 0.49). PMID- 1414939 TI - Long-term echocardiographic Doppler monitoring of Hancock bioprostheses in the mitral valve position. AB - Echocardiographic and Doppler studies were performed in 134 patients with a Hancock bioprosthesis in the mitral valve position during a follow-up period of 1 to 216 months. Among the xenografts, 57% were clinically normal and 43% had severe dysfunction. Among the normal bioprostheses, 35% had echocardiographically thickened mitral cusps (> or = 3 mm) with normal hemodynamic function; by setting the lower 95% confidence limit of valve area at 1.7 cm2 these patients had a significantly (p < 0.01) smaller valve area than that of normal control subjects. Evaluation of all thickened normal mitral valves showed the highest incidence of thickening at 9 years after implantation. Valve replacement surgery was subsequently performed in 33 patients with dysfunctioning bioprosthetic and echocardiographic diagnosis was confirmed in 91% of explanted valves (bioprosthetic stenosis 21%, incompetence 46%, and combined stenosis and regurgitation 33%). In 2 valves that were found to be stenotic on echocardiographic examination, a calcium-related commissural tear was also observed at reoperation, and in another, a paravalvular leak was found. Dystrophic calcification, isolated (64%) or occasionally associated with fibrous tissue overgrowth (21%), was the main cause of failure. Pannus was present in prostheses with longer satisfactory function (168 +/- 31 vs 124 +/- 21 months; p < 0.001). Long-term performance was evaluated by the Kaplan-Meier method for up to 18 years of follow-up. Freedom from structural valvular disfunction after mitral replacement was 89% at 6 years, 77% at 8 years, 56% at 10 years, 31% at 12 years, 16% at 15 years, and 15% at 18 years. PMID- 1414940 TI - A new, noninvasive method to monitor the aging of bioprosthetic valves in the mitral position. AB - Bioprosthetic valves undergo a tissue degeneration of unpredictable onset and amount. This process alters the structure and function of the valve and consequently shortens its lifespan. The echocardiographic technique usually used in the follow-up of these patients does not provide accurate information concerning the amount of prosthesis tissue degeneration. A new technique has been developed based on the spectral analysis of the first heart sound, which enables the evaluation of prosthetic leaflet stiffness. The Young's modulus (E) and stress (s) of the valve leaflets were derived as functions of the inner diameter of the heterograft and its primary vibration frequency, which can be obtained from the frequency spectrum of the first heart sound. Thirty-six patients with a mitral bioprosthetic valve were studied. Fifteen had thickening or calcification, or both, of the valvular leaflets at echocardiographic examination. In patients with a normal valve, E and s showed a good correlation with the duration of implantation (r = 0.909, p < 0.001; and r = 0.828, p < 0.001; respectively). Patients with abnormal leaflets had values of E and s that were greater than the theoretical values expected for their duration of implantation. The procedure is sensitive, accurate and easy to perform, and enables monitoring of the aging of the prosthetic valve and early identification of valve tissue degeneration. Together with echocardiography, this procedure yields a more complete evaluation of prosthetic valves for the follow-up of patients. PMID- 1414941 TI - Predictors, mechanisms and outcome of severe mitral regurgitation complicating percutaneous mitral valvotomy with the Inoue balloon. AB - During 241 consecutive percutaneous mitral valvotomy (PMV) procedures performed with the Inoue balloon, 16 patients (6.6%) developed severe mitral regurgitation (MR). Baseline clinical, echocardiographic (Doppler mitral valve area and Wilkins' score) and hemodynamic data were not different from those of patients without this complication. Severe MR occurred during the first inflation in 7 patients and after several stepwise inflations in 9. Although maximal balloon size was similar in both groups, unusual indentations and subvalvular inflations were more frequently observed in patients who developed severe MR. Early mitral valve replacement was required in 6 patients. All of them had a leaflet rupture either along the midportion (2 patients), along a commissure (4 patients), or both. Commissural calcium was present in 5 valves and 5 also had severe subvalvular involvement that had been underestimated by echocardiography. Of the 10 nonsurgically treated patients, 4 had chordal rupture by echocardiographic criteria, whereas in the remaining 6 the precise mechanism of MR could not be determined. During follow-up (11.4 +/- 4 months, range 1 to 30), 1 patient required surgery for symptoms and the remaining 9 were symptomatically improved and free of left ventricular dilatation. In conclusion, severe MR complicated 6.6% of PMV procedures with the Inoue balloon, and its mechanism was leaflet or chordal rupture. Although one third of the patients required early mitral surgery, most of the remaining obtained midterm symptomatic benefit. PMID- 1414942 TI - Effects of dobutamine on Gorlin and continuity equation valve areas and valve resistance in valvular aortic stenosis. AB - Previous studies demonstrated changes in aortic valve area calculated by the Gorlin equation under conditions of varying transvalvular flow in patients with valvular aortic stenosis (AS). To distinguish between flow-dependence of the Gorlin formula and changes in actual orifice area, the Gorlin valve area and 2 other measures of severity of AS, continuity equation valve area and valve resistance, were calculated under 2 flow conditions in 12 patients with AS. Transvalvular flow rate was varied by administration of dobutamine. During dobutamine infusion, right atrial and left ventricular end-diastolic pressures decreased, left ventricular peak systolic pressure and stroke volume increased, and systolic arterial pressure did not change. Heart rate increased by 19%, cardiac output by 38% and mean aortic valve gradient by 25%. The Gorlin valve area increased in all 12 patients by 0.03 to 0.30 cm2. The average Gorlin valve area increased from 0.67 +/- 0.05 to 0.79 +/- 0.06 cm2 (p < 0.001). In contrast, the continuity equation valve area (calculated in a subset of 6 patients) and valve resistance did not change with dobutamine. The data support the conclusion that flow-dependence of the Gorlin aortic valve area, rather than an increase in actual orifice area, is responsible for the finding that greater valve areas are calculated at greater transvalvular flow rates. Valve resistance is a less flow dependent means of assessing severity of AS. PMID- 1414943 TI - Prognostic implications of subclinical left ventricular dilatation and systolic dysfunction in men free of overt cardiovascular disease (the Framingham Heart Study). AB - To determine the prognostic significance of asymptomatic left ventricular (LV) dilatation and LV systolic dysfunction, 1,493 men who were free of symptomatic cardiovascular disease underwent M-mode echocardiography and were then followed for a mean of 4.15 years. At baseline examination, 170 men (11.4%) had an abnormally high end-diastolic LV internal dimension (> or = 56 mm) and 76 (5.1%) had an abnormally low fractional shortening (< or = 30%). During the follow-up period, 68 men experienced 92 cardiovascular disease events. After adjusting for age and traditional cardiovascular disease risk factors in proportional-hazards analyses, fractional shortening was a significant independent predictor of cardiovascular risk (relative risk [RR] = 1.42, 95% confidence interval [CI] 1.12 to 1.81, for decrease of fractional shortening by 4%). Increased risk was also associated with combinations of low fractional shortening and high end-diastolic internal dimension (RR = 3.77, 95% CI 1.59 to 8.93) and with low percent fractional shortening with LV hypertrophy (RR = 5.93, 95% CI 1.97 to 17.85). In conclusion, subclinical LV dilatation and LV systolic dysfunction, although uncommon in men free of overt cardiovascular disease, are associated with increased risk for new cardiovascular disease events. PMID- 1414944 TI - Left ventricular filling abnormalities in non-insulin-dependent diabetes mellitus and improvement by a short-term glycemic control. AB - To determine whether left ventricular (LV) filling abnormalities in diabetes are associated with diabetic microangiopathy, and to evaluate the effect of a short term glycemic control on the filling abnormalities, diastolic filling dynamics were assessed by pulsed Doppler echocardiography in 246 patients with non-insulin dependent diabetics. Isovolumic relaxation time and the ratio of peak flow velocity of atrial filling wave to peak flow velocity of early filling wave (A/E) were significantly greater in diabetic patients than in age- and sex-matched control subjects. Diabetic patients with retinopathy had significantly greater isovolumic relaxation time and A/E values than those without retinopathy. A/E was significantly decreased 1 month after insulin treatment in those without, but not with retinopathy. It is concluded that LV diastolic filling is impaired in mildly hyperglycemic patients with non-insulin-dependent diabetes mellitus without severe complications, the abnormality being more intense in patients with retinopathy. A short-term glycemic control results in a marked decrease in abnormalities in patients without, but not with retinopathy. PMID- 1414945 TI - Age-related increase in systolic fraction of pulmonary vein flow velocity-time integral from transesophageal Doppler echocardiography in subjects without cardiac disease. AB - The pulmonary vein flow velocity-time profile would be equivalent to the pulmonary vein flow volume-time profile, provided that the cross-sectional area of the pulmonary vein remains unchanged during 1 cardiac cycle. The systolic fraction of the pulmonary vein flow velocity-time integral, a ratio of velocity time integral of the S wave to the sum of velocity-time integrals of the S and D waves, represents the ratio of left atrial storage volume to left ventricular stroke volume. This systolic fraction may help early filling of the left ventricle through an appropriate storage of blood and generation of driving pressure in the left atrium. Because early filling of the left ventricle is progressively impaired with age, it was hypothesized that this systolic fraction is increased with age. Forty-four noncardiac surgical patients (age range 17 to 70 years) who underwent transesophageal Doppler echocardiography under general anesthesia were studied, and left upper pulmonary vein flow and mitral inflow velocities were recorded. The ratio of peak velocity of the E wave to that of the A wave of mitral inflow velocity-time profile (y) decreased with age (y = -0.0245 x age + 2.41; r = -0.672, p < 0.01). Systolic fraction (y) increased with age (y = 0.00373 x age + 0.514; r = 0.656, p < 0.01). The age-related increase in the systolic fraction of pulmonary vein flow velocity-time integral may account for the compensation for impaired early filling of the left ventricle in elderly patients. PMID- 1414946 TI - Frequency of long-term lower limb ischemia associated with intraaortic balloon pump use. AB - Lower limb ischemia is a frequent complication of intraaortic balloon pump (IABP) use. The incidence and risk factors for acute ischemia have been well-defined, but little is known about long-term ischemic complications. This prospective study evaluated the incidence, nature, progression and predisposing factors for long-term lower limb ischemia in 151 patients who were previously treated with the IABP. These persons were interviewed and their lower extremities examined 12 to 20 months after undergoing IABP counterpulsation. Limb ischemia, characterized primarily by ipsilateral discomfort and diminished pulses, occurred in 18% of those evaluated. Evidence of ischemia worsened over time in 14%. Logistic regression analysis, which was based on variables found to be significant in bivariate analysis, revealed that the occurrence of limb ischemia acutely, cardiogenic shock as an indication for IABP insertion, and smoking (at the time of hospitalization or having quit < 10 years previously) were risk factors for long-term lower limb ischemia. The adjusted odds ratio for acute limb ischemia was 8.89 (95% confidence interval 2.80 to 28.21), for cardiogenic shock 3.59 (95% confidence interval 1.01 to 12.75), and for smoking 2.87 (95% confidence interval 1.10 to 7.46). Increasing numbers of patients are undergoing IABP counterpulsation and a greater proportion of these are surviving their acute event and resuming active lives. It is essential to recognize that detrimental consequences of this device can persist long after hospitalization. PMID- 1414947 TI - Automated, on-line quantification of left ventricular dimensions and function by echocardiography with backscatter imaging and lateral gain compensation. AB - To provide on-line quantification of left ventricular cavity dimensions and function by echocardiography 60 control subjects and 10 patients with cardiac dysfunction were studied. A novel, ultrasound imaging system was used which was developed to detect and track, in real time, ventricular endocardial blood boundaries based on quantitative assessment of acoustic properties of tissue. In addition, lateral gain compensation, a robust and novel image enhancement procedure, was used to provide instantaneous measurement and display of cavity areas and functional indexes on a beat-by-beat basis within regions of interest drawn around the blood pool cavity. In control subjects, short-axis end-diastolic area averaged 13.1 +/- 3.7 cm2 (SD), end-systolic area 5.9 +/- 2.7 cm2, and fractional area change 55.6 +/- 11.2%. Apical views yielded corresponding values of 23.8 +/- 4.5 cm2, 15.5 +/- 3.4 cm2 and 34.7 +/- 7.8%. Instantaneous peak rate of cavity area change approximated 50 cm2/s in systole and 60 cm2/s in diastole in each view. Serial measurements of area and functional index were reproducible over intervals of 2 to 3 weeks. Patients with dilated ventricles exhibited average apical view area values of 49.1 +/- 6.1 cm2 and 43.1 +/- 4.9 cm2 in diastole and systole with a fractional area change of 12.2 +/- 3.0%. Thus, results with on-line echocardiographic backscatter imaging-assisted automated edge detection are reproducible and capable of delineating cardiac dysfunction conveniently, promptly and serially at the bedside. PMID- 1414948 TI - Effects of quinidine and amiodarone on blood pressure during rapid ventricular pacing in coronary artery disease. PMID- 1414949 TI - Prevalence of atherothrombotic brain infarction, coronary artery disease and peripheral arterial disease in elderly blacks, Hispanics and whites. PMID- 1414950 TI - Age at onset and gender of patients with different types of supraventricular tachycardias. PMID- 1414951 TI - Effect of mitral valve repair for mitral valve prolapse on regression of left ventricular mass. PMID- 1414952 TI - Activation of the coagulation system in women with mitral stenosis and sinus rhythm. PMID- 1414953 TI - Prevalence of bilateral patent ductus arteriosus in patients with pulmonic valve atresia and asplenia syndrome. PMID- 1414954 TI - Localized left ventricular aneurysms with normal global function caused by myocarditis. PMID- 1414955 TI - ST-alternans alternans. PMID- 1414956 TI - Tricyclic overdose causing sustained monomorphic ventricular tachycardia. PMID- 1414957 TI - Myocardial respiratory chain enzyme activities in anomalous origin of the left main coronary artery from the pulmonary trunk (Bland-White-Garland syndrome) and comparison with atherosclerotic coronary artery disease. PMID- 1414958 TI - Creatinine arm index as alternative for creatinine height index. AB - Nutritional assessment of elderly people is limited due to a lack of age corrected standards. The objective of this study was to develop a new, more age independent index for nutritional assessment by correcting the creatinine height index (CHI) for the age-induced changes in its variables. This might improve the differentiation between physiological reduction in muscle mass in elderly people and the changes induced by malnutrition. Seventy-four elderly and 100 young healthy volunteers were compared by anthropometric and biochemical-assessment variables. From the high correlation between total arm length and body length (r = 0.86; P less than 0.001) and the use of an alternative formula to calculate ideal body weight (IBW) from height and wrist circumference, a relatively age independent estimate of IBW was determined. Creatinine arm index, as an adapted index of CHI, is proposed based on this age-independent IBW estimation and a specific creatinine coefficient for different age groups. PMID- 1414959 TI - Dietary fat and body fat: a multivariate study of 205 adult females. AB - This study examined the association between diet composition, particularly dietary fat intake, and body-fat percentage in 205 adult females. Subjects completed a written questionnaire regarding lifestyle factors, such as exercise participation and smoking, demographic data, and the diet section of the National Cancer Institute's Health Habits and History Questionnaire by Block. Skinfold thickness measures were used to ascertain the body-fat percentage of each subject. Results showed that intake of dietary fat was related significantly with adiposity, without (F = 13.65, R2 = 0.063, P = 0.0003) and with (F = 8.74, R2 = 0.033, P = 0.0035) control for multiple potential confounding factors: age, total energy intake, total exercise time per week, years of regular physical activity, consumption of other macronutrients, and smoking. Unlike dietary fat intake, protein consumption and carbohydrate intake were not significant individual predictors of body-fat percentage when the potential confounding variables were controlled. The findings suggest that dietary fat intake may play a role in obesity beyond dietary energy content. PMID- 1414960 TI - Basal metabolic rate of Colombian children 2-16 y of age: ethnicity and nutritional status. AB - Measurements of basal metabolic rate (BMR) were made in 528 children 2-16 y of age living in underprivileged areas of the city of Cali, Colombia (153 control and 186 undernourished boys, 93 control and 96 undernourished girls). The data are related to BMR calculated from the equations of Schofield and to estimates of the lean body mass (LBM). The ethnic composition of the subjects was 80% mestizo (mixed European and South Amerindian ancestry), 15% black, and 5% white. The data do not show any variations due to race in these subjects. The Schofield equations overestimate the BMR of boys by approximately 6% whereas the estimation of BMR in girls is not significantly different from measured values. More than 65% of the variation in BMR of both nutritionally normal and undernourished boys and girls is explained by variation in body size as estimated by the LBM. PMID- 1414961 TI - Body composition, energy utilization, and nitrogen metabolism with a 4.25-MJ/d low-energy diet supplemented with pyruvate. AB - We measured body composition, energy deficit, and nitrogen metabolism in 14 obese women housed in a metabolic ward, who consumed a 4.25-MJ/d liquid diet (68% carbohydrate, 22% protein) for 21 d with or without pyruvate (PY; n = 7) partially, isoenergetically substituted for glucose (placebo; n = 7). Body composition and leucine oxidation and turnover were determined before and after weight loss. Energy deficit was calculated from resting metabolic rates. Subjects fed pyruvate showed a greater weight loss (PY = 5.9 +/- 0.7 kg, placebo = 4.3 +/- 0.3 kg, P less than 0.05), fat loss (PY = 4.0 +/- 0.5 kg, placebo = 2.7 +/- 0.2 kg, P less than 0.05), kg wt loss/4.25-MJ deficit (PY = 0.22 +/- 0.01 kg, placebo = 0.17 +/- 0.01 kg, P less than 0.05, and kg fat loss/4.25-MJ deficit (PY = 0.15 +/- 0.01 kg, placebo = 0.11 +/- 0.01 kg, P less than 0.05). Nitrogen balance (urine and stool) and leucine oxidation and turnover were similar in both groups. We conclude that the dietary modification whereby the three-carbon compound pyruvate is isoenergetically substituted for the six-carbon compound glucose in a 4.25-MJ/d, low-energy diet will increase fat and weight loss. PMID- 1414962 TI - Body composition, nitrogen metabolism, and energy utilization with feeding of mildly restricted (4.2 MJ/d) and severely restricted (2.1 MJ/d) isonitrogenous diets. AB - To determine the effects on weight loss of feeding isonitrogenous diets in mildly restricted (4.2 MJ/d) and severely restricted (2.1 MJ/d) amounts, we measured body composition, weight loss-energy deficit ratio, and nitrogen metabolism in 14 obese women housed in a metabolic ward consuming hypoenergetic diets for 21 d. Subjects consumed either a 4.2-MJ/d diet (50 g protein, 175 g carbohydrate) or a 2.1-MJ/d diet (50 g protein, 75 g carbohydrate). Body composition and leucine oxidation and turnover were determined before and after weight loss. Energy deficit was calculated from resting metabolic rates. Subjects fed the 2.1-MJ/d diet showed a greater weight loss (6.1 +/- 0.5 vs 4.5 +/- 0.5 kg; mean +/- SE, P less than 0.05) and fat loss (3.9 +/- 0.3 vs 3.0 +/- 0.3 kg, P less than 0.05). Weight loss-energy deficit ratio was the same with both diets. Nitrogen balance and leucine oxidation and turnover were similar in both groups. We conclude that with feeding of isonitrogenous hypoenergetic diets, severe restriction of energy content (2.1 MJ/d, 75 g carbohydrate) will enhance weight and fat loss without increasing nitrogen loss compared with mild restriction of energy (4.2 MJ/d). PMID- 1414963 TI - Metabolic response to experimental overfeeding in lean and overweight healthy volunteers. AB - Possible adaptive mechanisms that may defend against weight gain during periods of excessive energy intake were investigated by overfeeding six lean and three overweight young men by 50% above baseline requirements with a mixed diet for 42 d [6.2 +/- 1.9 MJ/d (mean +/- SD), or a total of 265 +/- 45 MJ]. Mean weight gain was 7.6 +/- 1.6 kg (58 +/- 18% fat). The energy cost of tissue deposition (28.7 +/- 4.4 MJ/kg) matched the theoretical cost (26.0 MJ/kg). Basal metabolic rate (BMR) increased by 0.9 +/- 0.4 MJ/d and daily energy expenditure assessed by whole-body calorimetry (CAL EE) increased by 1.8 +/- 0.5 MJ/d. Total free-living energy expenditure (TEE) measured by doubly labeled water increased by 1.4 +/- 2.0 MJ/d. Activity and thermogenesis (computed as CAL EE--BMR and TEE--BMR) increased by only 0.9 +/- 0.4 and 0.9 +/- 2.1 MJ/d, respectively. All outcomes were consistent with theoretical changes due to the increased fat-free mass, body weight, and energy intake. There was no evidence of any active energy-dissipating mechanisms. PMID- 1414964 TI - Gastric capacity, gastric emptying, and test-meal intake in normal and bulimic women. AB - The role of the stomach in regulating appetite in bulimia nervosa was examined. Subjects were nine normal and nine bulimic women of similar age, height, and weight. Gastric capacity was estimated by filling a balloon in the stomach. The mean stomach capacity of bulimic subjects was significantly larger than that of normal subjects, as revealed by the larger balloon volume tolerated (P less than 0.01) and by the larger volume needed to produce a 5 cm H2O increase in intragastric pressure (P = 0.07). The intake of a liquid meal was also significantly larger for the bulimic subjects. Gastric-emptying rate of a liquid meal was significantly delayed in the bulimic subjects during the initial 5-15 min. In all subjects, test-meal intake correlated significantly with gastric capacity (r = 0.53). In the bulimic subjects, self-reported binge intake (J) also correlated significantly with gastric capacity (r = 0.75). Binge eating in bulimic subjects may enlarge gastric capacity, which could then promote even larger binges through positive feedback. PMID- 1414965 TI - A 24-h energy expenditure study on reduced-obese and nonobese women: effect of beta-blockade. AB - Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were studied in a respiration chamber in 15 reduced-obese (BMI = 24.7) and 8 nonobese (BMI = 20.1) women. Two experiments were performed, one in which beta-blockade was introduced by propranolol and one with placebo. When adjusted for differences in fat-free mass, no difference in 24-h EE was found between the reduced-obese and nonobese groups in placebo experiments. Propranolol reduced 24-h EE by 2.7% in the reduced-obese group whereas no reduction was seen in the nonobese group. A positive correlation was found between fasting glycerol concentration and lipid oxidation. During daytime, lipid oxidation was reduced and carbohydrate oxidation increased by propranolol only in the nonobese subjects. Propranolol reduced fasting glycerol and free fatty acid concentrations in both groups. Beta-blockade seems to have little effect on sedentary 24-h EE but may have a suppressing effect on lipid combustion. PMID- 1414966 TI - Comparison of the effects on lipoproteins and apolipoproteins of a diet high in monounsaturated fatty acids, enriched with avocado, and a high-carbohydrate diet. AB - A randomized trial was conducted to compare effects of a diet high in monounsaturated fatty acids, enriched with avocado (AE), and a high-complex carbohydrate diet (AHA-III) on blood lipid concentrations. Fifteen females between 37 and 58 y of age were allocated either to AE followed by AHA-III, or vice versa. Each dietary phase lasted 3 wk. Both diets were found to lower total cholesterol compared with baseline values. AE was more effective, with an 8.2% decrease (P less than 0.05) whereas AHA-III was associated with a 4.9% decrease (NS). Low-density-lipoprotein cholesterol and apolipoprotein B decreased significantly on AE but not on AHA-III (P less than 0.05). The high-density lipoprotein (HDL) concentration did not change on AE but decreased 13.9% on AHA III (P less than 0.01). It is concluded that AE is more effective than is AHA-III in decreasing total cholesterol, and, unlike AHA-III, it does not decrease HDL concentrations. PMID- 1414967 TI - Comparative effects of a recommended lipid-lowering diet vs a diet rich in monounsaturated fatty acids on serum lipid profiles in healthy young adults. AB - This crossover study investigated the effects of two fat-reduced diets, one rich in monounsaturated fatty acids (MUFAs), the other rich in polyunsaturated fatty acids (PUFAs), on serum lipid profiles in 38 healthy young adults initially on a typical western diet. After being randomly assigned to two groups, the subjects received the MUFA or PUFA diet for 3-wk and then the other diet for 3 wk. Both test diets led to significant reductions in serum cholesterol, LDL cholesterol, and HDL cholesterol (P less than 0.001). Both reduced apolipoprotein B (P less than 0.001) and apolipoprotein A-I concentrations (P less than 0.01 for the MUFA, P less than 0.001 for the PUFA diet). Apolipoprotein A-I was significantly higher on the MUFA than on the PUFA diet. The ratio of apolipoprotein A-I to B significantly increased on both diets. Thus, a low-fat, MUFA-rich diet is as effective as a low-fat, PUFA-rich diet in lowering total and LDL cholesterol, but both also lowered HDL cholesterol concentrations. The MUFA-rich diet may be more advantageous than the PUFA-rich one because it does not lower apolipoprotein A-I concentrations as much as the PUFA-rich diet. PMID- 1414968 TI - Effect of beta-carotene supplementation on photosuppression of delayed-type hypersensitivity in normal young men. AB - The aim of this study was to examine whether beta-carotene protects against the immunosuppression seen with long-wave ultraviolet-light (UV-A) exposure. Free living, healthy men, aged 19-39 y received 30 mg beta-carotene/d or a placebo while on a single-menu, low-carotenoid diet. After 28 d all subjects received 12 exposures to a UV-A/B light source over a 16-d period. The total UV-A dose received ranged from 15.9 to 19.3 J/cm2. The total shorter-wave ultraviolet-light (UV-B) dose varied from 1.59 to 1.96 J/cm2. Follow-up continued for 21 d. Carotenoid assays and delayed-type hypersensitivity (DTH) tests were performed at baseline, pre-UV, post-UV, and after follow-up. The DTH-test responses were significantly suppressed in the placebo group after UV treatments. The suppression was inversely related to plasma beta-carotene concentrations in this group. There was no significant suppression of DTH test responses in the beta carotene group. It is concluded that beta-carotene protects against photosuppression of immune function. PMID- 1414969 TI - Prediction of iron absorption based on iron status of female blood donors. AB - Iron stores were assessed in 27 postmenopausal healthy women who donated five units of blood (approximately 485 mL/unit) over approximately 1 y. The mean (+/- SD) age was 67.7 +/- 4.0 y and the average time between successive blood donations was approximately 10 wk (range 8-30 wk). Steady-state iron stores at entrance were 10.59 +/- 3.88 mg/kg body wt (mean +/- SD) and declined to 1.03 +/- 3.20 mg/kg by the fifth donation. Determination of iron stores was based on biochemical measures of iron status at each donation. Iron intakes were 23.3 +/- 10.1 mg/d. From these data we developed equations that can be used to predict the frequency at which healthy postmenopausal women can donate blood without becoming iron deficient. The ability of elderly women to become successful blood donors depends primarily on initial iron stores, iron intake, and frequency of donation. Women with low steady-state iron stores may be able to donate only two times per year without becoming iron deficient. PMID- 1414970 TI - Axial and peripheral bone density and nutrient intakes of postmenopausal vegetarian and omnivorous women. AB - The study investigated whether differences exist between postmenopausal Caucasian vegetarian and omnivorous women regarding trabecular and cortical bone density measured with single- and dual-photon absorptiometry. Anthropometric measurements, blood and urine samples, and food intakes of the twenty-eight matched pairs were also compared. The Wilcoxon signed-rank test indicated no significant differences in bone measurements between vegetarians and omnivores at any sites except the skull. The vegetarians' serum globulin and total protein measured higher. Urine calcium and creatinine were similar between the groups. The vegetarians consumed greater quantities of carbohydrate, fiber, magnesium, ascorbic acid, copper, and energy as percent carbohydrate, and lower quantities of protein, niacin, alcohol, vitamin B-12, cholesterol, and energy as percent protein. Despite several differences in dietary intakes, the results indicate that neither cortical nor trabecular bone density in these postmenopausal women was affected by a lactoovovegetarian diet. PMID- 1414971 TI - Dietary patterns, eating behaviors, and bone mineral density in women runners. AB - Although reduced gonadal steroid hormone concentrations appear to play a major role in lower trabecular bone mineral density (BMD) in women with athletic amenorrhea, dietary deficiencies and eating behaviors may also affect BMD in women runners. To investigate this possibility, dietary patterns (7-d records), eating-disorders inventory (EDI), and BMD were examined in nine nonrunning eumenorrheic control (Contl) and 32 women runners classified as eumenorrheic (n = 19, Eumen) and oligo/amenorrheic (a group in which some were oligomenorrheic and some were amenorrheic; Ol/Am, n = 13). Runner groups had similar cardiorespiratory fitness, body composition, and training characteristics. Lumbar spine BMD was lower in the Ol/Am runners (-12%, P less than 0.05) but proximal femur BMD did not differ. Dietary intake and EDI subscale scores were similar among the groups. However, there was an inverse trend between EDI subscale scores for bulimia and ineffectiveness and femoral BMD in the Ol/Am runners (r = -0.62 to -0.71, P less than 0.05). These results suggest that self-reported dietary intake and/or eating behaviors do not predict reproductive-function alterations in women runners, but eating behaviors may be associated with lower BMD in Ol/Am runners. PMID- 1414972 TI - Blood glucose and insulin responses to different meals in non-insulin-dependent diabetic subjects of both sexes. AB - The influence of sex on glucose and insulin responses in patients with non insulin-dependent diabetes was studied in 12 men and 11 matched women. Two meals of either 100 g white bread or 60 g (raw weight) white rice were given. Blood glucose response areas to white bread (517 vs 509 mmol/L) and to rice (306 vs 353 mmol/L) over a 300-min observation period were similar in females and males, respectively. Insulin responses showed an identical pattern to that of glucose in females and males--35784 vs 28230 pmol/L after white bread and 28044 vs 19464 pmol/L min after rice (NS) over a 300-min observation period, respectively. Within the two study groups, blood glucose-response areas to white bread were significantly higher than those to rice (P less than 0.05), whereas there were no differences in insulin-response areas within or between the two groups. The glycemic index of rice for females (62 +/- 9; mean +/- SE) and males (66 +/- 5) was similar. PMID- 1414973 TI - Value of Food and Agriculture Organization data on food-balance sheets as a data source for dietary fat intake in epidemiologic studies. AB - The relationships between the per person supply (expressed as percent of total energy supply) of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) obtained from 1979-1981 Food and Agriculture Organization (FAO) data, and the per person intake obtained from 52 individual dietary surveys performed in 19 countries, were examined. In particular, the ratio of PUFAs to SFAs (P:S) and the ratio of unsaturated fatty acids (MUFAs and PUFAs) to SFAs (U:S) obtained from both data sources were examined. Significant correlations (P less than 0.001) were found between the two data sources for the P:S, U:S, SFAs, and MUFAs and PUFAs (P less than 0.02) in 19 countries. It is concluded that the data on fat intake from the FAO are valid for use in epidemiologic studies. In view of the variability of the data, it is recommended to use them either expressed as percentage of energy or as ratios of the different components. PMID- 1414974 TI - Herman Award Lecture, 1992: lipid nutrition--a personal perspective. AB - In the 1950s excess dietary fat was thought to be a risk factor for development of atherosclerosis. Over the ensuing years we have examined and given advice concerning first, saturation and unsaturation, and later, specific fatty acids such as oleic and stearic acids. Current work is further refining the delineation of fatty acids that might be harmful. Eventually, we will probably again cite excess fat as the problem. PMID- 1414975 TI - McCollum Award Lecture, 1992: vitamin A absorption, transport, cellular uptake, and storage. AB - We discuss vitamin A with emphasis on its absorption, transport, cellular uptake, storage, and intracellular metabolism. Dietary retinyl esters are hydrolyzed to retinol in the intestinal lumen before absorption by enterocytes. Carotenoids are absorbed and then partially converted to retinol in the enterocytes. In enterocytes retinol is esterified before incorporation into chylomicrons together with triacylglycerols. Chylomicrons reach the general circulation by way of the intestinal lymph, and chylomicron remnants are formed in the blood capillaries. The remnants, which contain almost all the absorbed retinol, are cleared by the liver parenchymal cells, and to some extent also by cells in blood, bone marrow, adipose tissue, and spleen. The uptake is most probably mediated via surface receptors for low-density lipoproteins or a low-density lipoprotein-receptor related protein. In the liver parenchymal cells the retinyl esters are rapidly hydrolyzed to retinol, which binds to retinol-binding protein. Normally, most of the absorbed retinol coming into the liver parenchymal cell is transferred on retinol-binding protein to stellate cells, which store retinol as retinyl esters in lipid droplets. PMID- 1414976 TI - National Dairy Council Award for Excellence in Medical/Dental Nutrition Education Lecture, 1992: perspectives on nutrition in medical education. PMID- 1414977 TI - Weight cycling and cardiovascular risk in obese men and women. PMID- 1414978 TI - Why is the Food and Drug Administration interested in dietary fatty acids and thrombosis? PMID- 1414980 TI - Does a prethrombotic state exist? If so, what is it? PMID- 1414979 TI - What is the historical background of research on the role of fatty acids in thrombosis? PMID- 1414981 TI - Why is platelet activation useful for assessing thrombotic risk? What are the advantages and limitations of using flow cytometry to measure platelet activation? PMID- 1414982 TI - Why is lipoprotein(a) relevant to thrombosis? PMID- 1414983 TI - What are current approaches to studying lipoprotein metabolism as it relates to thrombosis? PMID- 1414984 TI - Can changes in dietary fatty acid intake lead to changes in physiologic responses related to thrombosis? PMID- 1414985 TI - What is the metabolic fate of dietary long-chain fatty acids (especially stearic acid) in normal physiological states, and how might this relate to thrombosis? PMID- 1414986 TI - Do dietary fatty acids affect the biophysics of platelet-membrane function in thrombosis? PMID- 1414987 TI - What are the effects of dietary fatty acid modification on platelet eicosanoid metabolism, platelet-activating factor, and platelet function? How might these metabolic alterations influence thrombosis? PMID- 1414988 TI - Do dietary fatty acids cause endothelial activation? How might endothelial activation contribute to thrombogenesis? PMID- 1414989 TI - Do dietary fatty acids affect endothelial cell production of growth factors? How might these factors relate to thrombogenesis? PMID- 1414990 TI - Do dietary fatty acids affect intra- and intercellular signalling? How might these processes affect thrombosis? PMID- 1414991 TI - Do dietary fatty acids affect the interactions among macrophages, endothelial lesions, and thrombosis? PMID- 1414992 TI - What are the abnormal responses in the arterial wall of individuals with atherosclerosis? Does evidence exist linking dietary fatty acids to these responses? PMID- 1414993 TI - What are the abnormal thrombotic responses in the clotting system of individuals with atherosclerosis? Are these responses genetically determined or adaptations to the disease state? PMID- 1414994 TI - Which surrogate endpoints are valid for assessing thrombotic tendency? PMID- 1414995 TI - Do dietary fatty acids affect platelet aggregation and arterial thrombosis tendency in a rat model? PMID- 1414996 TI - What are the effects of dietary n-3 fatty acids on vascular thrombus and lesion formation in nonhuman primates? PMID- 1414997 TI - Do dietary fatty acids affect the composition of the fatty acids of platelets and platelet function? PMID- 1414998 TI - What is the clinical evidence for a thrombogenic potential of dietary long-chain fatty acids? PMID- 1414999 TI - What is the epidemiologic evidence for the thrombogenic potential of dietary long chain fatty acids? PMID- 1415000 TI - Relationship of catecholamine excretion to body size, obesity, and nutrient intake in middle-aged and elderly men. AB - Catecholamine release from sympathetic nerves and the adrenal medulla is influenced by diet under controlled research conditions. To test whether diet affects catecholamine excretion in free-living men, the urinary content of dopamine (DA), epinephrine (Epi), or norepinephrine (NE) was measured in 24-h collections provided by 572 participants of the Normative Aging Study of the Veterans Administration. Average daily intakes of energy and macronutrients were assessed by means of a semiquantitative food frequency questionnaire and sodium intake by quantitation of sodium excretion. Catecholamine excretion was also examined in relation to anthropometric variables. Because DA and Epi excretion were inversely related to age, all subsequent analyses included adjustments for age. Although DA and NE were positively related to measures of body size and fatness, Epi was negatively related to body fatness. Excretion rates of all three catecholamines were directly related to total energy intake and inversely related to energy-adjusted CHO consumption. PMID- 1415001 TI - Is the impedance index (ht2/R) significant in predicting total body water? AB - We investigated the general utility of bioelectrical impedance analysis (BIA) and the implications of BIA theory in populations of various ages from infancy to adulthood by developing a single impedance equation. Four subject data sets representing 62 adults, 37 prepubertal children, 44 preschool children, and 32 premature low-birth-weight neonates were combined. Subjects were randomly divided into a development group (n = 116) and a cross-validation group (n = 59). The single best predictor of total body water (TBW) was height2/resistance (ht2/R), which explained 99% of the variation in TBW (SEE = 1.67 kg). The addition of weight reduced the SEE to 1.41 kg. A significant bias was only seen in the preschool children. These results were confirmed in the cross-validation group and the best prediction formula was TBW = 0.59 ht2/R + 0.065 wt + 0.04. We conclude that the impedance index (ht2/R) is a significant predictor of TBW and that there is some improvement in prediction of TBW by inclusion of a weight term. PMID- 1415002 TI - Lean-body-mass composition and resting energy expenditure before and after long term overfeeding. AB - This report deals with the association between the constituents of lean body mass (LBM) and resting metabolic rate (RMR) before and after a 100-d overfeeding period. Computed-tomography (CT) scan of 22 young adult males at nine different body levels were used to estimate adipose tissue mass (ATMCT), LBMCT, skeletal muscle mass (SMMCT), and non-muscular LBMCT (NM-LBMCT). Before overfeeding, all body constituents, except ATMCT, were significantly correlated with RMR. Only body mass changes were significantly correlated with RMR changes. Comparison of these results with those of several studies in the literature reveals that the relationship between RMR and fat-free mass is highly influenced by the size of the SD for the latter variable. In stepwise-multiple-regression analysis, only SMMCT could be used to predict RMR. It was concluded that SMMCT and ATMCT, but not NM-LBMCT, increased during overfeeding and that the best correlates of RMR remain LBMCT, SMMCT, and body mass. PMID- 1415003 TI - Prediction of resting energy expenditure from fat-free mass and fat mass. AB - On the basis of literature values, the relationship between fat-free mass (FFM), fat mass (FM), and resting energy expenditure [REE (kJ/24 h)] was determined for 213 adults (86 males, 127 females). The objectives were to develop a mathematical model to predict REE based on body composition and to evaluate the contribution of FFM and FM to REE. The following regression equations were derived: 1) REE = 1265 + (93.3 x FFM) (r2 = 0.727, P < 0.001); 2) REE = 1114 + (90.4 x FFM) + (13.2 x FM) (R2 = 0.743, P < 0.001); and 3) REE = (108 x FFM) + (16.9 x FM) (R2 = 0.986, P < 0.001). FM explained only a small part of the variation remaining after FFM was accounted for. The models that include both FFM and FM are useful in examination of the changes in REE that occur with a change in both the FFM and FM. To account for more of the variability in REE, FFM will have to be divided into organ mass and skeletal muscle mass in future analyses. PMID- 1415004 TI - Overfeeding and energy expenditure in humans. AB - The effect of overfeeding on energy expenditure was investigated in 23 young men subjected to a 353-MJ energy intake surplus over 100 d. The major part of this excess (222 MJ) was stored as body energy. The increase in energy cost of weight maintenance amounted to 52 MJ and was proportional to body weight gain. When it was added to the obligatory cost of fat and fat-free mass gains, the overall increase in energy expenditure amounted to a mean of 100 MJ. Four months after overfeeding, subjects had lost 82%, 74%, and 100% of the overfeeding gain in body weight, fat mass, and fat-free mass, respectively. We conclude that 1) in response to overfeeding, two-thirds of the excess energy intake is stored as body energy; 2) overfeeding induces an increase in energy cost of weight maintenance proportional to body weight gain, and 3) preoverfeeding energy balance tends to be restored when nonobese individuals return to their normal daily-life habits. PMID- 1415005 TI - Weight gain in adolescents during pregnancy: rate related to birth-weight outcome. AB - This study of 459 subjects from prenatal clinics for teenagers at three universities across the United States, addresses questions about gestational weight gain in adolescents raised by the 1990 Institute of Medicine Report. Rate and pattern of gain, independent of pregravid weight, are based on serial measures of mothers with favorable and unfavorable outcomes. Rate of gain (determined by using regression statistics) from weeks 15 to 40 was 0.588, 0.510, and 0.488 kg/wk for mothers of term infants weighing 3000-4000 g, term infants weighing < 3000 g, and preterm infants, respectively. The significantly lower percentage of infants weighing 3000-4000 g vs < 3000 g needing intensive care at birth (6% vs 15%, respectively, P < 0.05) further indicates the superior outcome among mothers with higher rates of gain. Rate of gain of mothers of infants weighing 3000-4000 g (favorable outcome) equaled the highest amount provisionally recommended, suggesting that restricting natural gain of adolescents to recommended rates may result in smaller than optimal infants. PMID- 1415006 TI - Energy intake, energy expenditure, and body composition of poor rural Philippine women throughout the first 6 mo of lactation. AB - Between 6 and 30 wk postpartum, body weight and body-fat mass of 40 healthy, rural, lactating Filipino women decreased by 1.5 (P < 0.05) and 0.7 kg (P < 0.05), respectively. Energy intake decreased slightly (NS) from 8.84 +/- 2.05 MJ/d (2113 +/- 489 kcal/d; mean +/- SD) at 6 wk to 8.67 +/- 2.37 MJ/d (2073 +/- 566 kcal/d) at 30 wk. Basal metabolic rate (BMR) remained unchanged throughout lactation, and physical-activity level increased significantly (P < 0.05) from 1.61 +/- 0.17 x BMR at 6 wk to 1.97 +/- 0.18 x BMR at 30 wk. Energy intakes at 6 and 30 wk of lactation were 1.02 and 0.77 MJ/d (244 and 185 kcal/d) higher (P < 0.05), respectively, than in early pregnancy. At ages 1-6 mo, mean weights and lengths of mainly breast-fed infants had Z scores between 0 and -1. By using the growth patterns of the breast-fed infants as proxy indicators for adequacy of lactational performance, this study suggests that present recommended energy intakes for lactation are too high for healthy Filipino women who show adequate lactational performance. PMID- 1415007 TI - Plasma lipids and lipoproteins during 6 d of maintenance feeding with long-chain, medium-chain, and mixed-chain triglycerides. AB - This study assessed fasting plasma lipids and lipoproteins and postprandial plasma lipids in healthy male subjects fed liquid-formula diets containing 40% of total energy as long-chain (LCT, primarily C18:1 and C18:2), medium-chain (MCT, C8:0-C10:0), or mixed-chain (structured lipid, STL, mostly C8:0, C10:0, and C22:0) triglycerides for 6 d. None of the diets altered plasma cholesterol concentrations. HDL cholesterol was decreased 14% by the STL diet (P < 0.044) and 15% by the MCT diet (P < 0.004) but was unchanged by the LCT diet. Plasma triglycerides were elevated 42% by the MCT diet (P < 0.006), but were unaltered by either the STL or LCT diets. Neither the STL nor the MCT diets produced changes in fasting lipoprotein lipid composition; however, during the LCT diet, VLDLs became enriched in triglyceride and LDLs became enriched in cholesterol. Postprandial triglyceridemia was significantly greater after subjects consumed the LCT diet than it was after they consumed either the STL or MCT diets, which were similar. Short-term feeding of MCT and STL diets produces significant changes in lipid metabolism. An understanding of the long-term effects of these diets awaits further study. PMID- 1415009 TI - Leucine kinetics after a brief fast and in response to feeding in premature infants. AB - To examine how feeding affects changes in leucine and protein metabolism, leucine kinetics were determined in nine preterm infants (32 +/- 2 wk gestation; mean +/- SD) after a brief fast and again during hourly feedings. Rates of leucine oxidation were similar during the fasting and feeding periods (31 +/- 4 vs 37 +/- 6 mumol.kg-1.h-1; mean +/- SE). The nonoxidative disposal rates of leucine (a reflection of protein synthesis) were also similar during both periods (228 +/- 20 vs 205 +/- 10 mumol.kg-1.h-1; mean +/- SE). In contrast, the rates of leucine release from endogenous protein (an indication of protein breakdown) were significantly reduced by feeding (259 +/- 23 vs 185 +/- 11 mumol.kg-1.h-1; mean +/- SE, P = 0.02). A significant positive correlation was demonstrated between the fasting rate of leucine release from endogenous protein and the degree of suppression produced by feeding (r2 = 0.796, P = 0.001). Conversely, a significant inverse correlation was shown between the nonoxidative disposal rate of leucine during fasting and the increase in response to feeding (r2 = 0.848, P < 0.001). These data suggest that premature infants respond to feeding after a brief fast by suppressing protein breakdown, rather than by increasing protein synthesis, and changes in protein metabolism produced by feeding in premature newborns may be influenced by the prevailing rates of protein breakdown and synthesis during fasting. PMID- 1415008 TI - Comparison of effects of lauric acid and palmitic acid on plasma lipids and lipoproteins. AB - The effects of lauric acid (C12:0) on plasma lipids and lipoproteins were compared with the effects of palmitic acid (C16:0) and oleic acid (C18:1) in a metabolic-diet study of 14 men by using liquid-formula diets fed for 3 wk each in random order. Lauric acid was supplied in a synthetic high-lauric oil, palmitic acid was provided by palm oil and oleic acid in oleic-rich sunflower seed oil. The high-lauric oil resulted in higher concentrations of plasma total cholesterol (4.94 +/- 0.75 mmol/L [mean +/- SE]) and LDL cholesterol (3.70 +/- 0.57 mmol/L) when compared with high-oleic sunflower oil (4.44 +/- 0.54 and 3.31 +/- 0.44 mmol/L, respectively), but did not raise total and LDL cholesterol concentrations as much as did palm oil (5.17 +/- 0.65 and 3.93 +/- 0.51 mmol/L, respectively). No differences were noted in plasma triglycerides or HDL cholesterol. Lauric acid raises total and LDL cholesterol concentrations compared with oleic acid, but is not as potent for increasing cholesterol concentrations as is palmitic acid. PMID- 1415010 TI - Vitamin B-6 depletion followed by repletion with animal- or plant-source diets and calcium and magnesium metabolism in young women. AB - An 84-98-d study was conducted in young women to determine the effect of vitamin B-6-deficient diets on calcium and magnesium metabolism. A vitamin B-6-deficient formula diet fed initially was followed by either animal- or plant-source protein food diets containing four increasing amounts of vitamin B-6. Calcium balance was negative during vitamin B-6 depletion. Serum calcium was higher and calcium balance negative with the plant protein diets. Magnesium balance was negative during vitamin B-6 depletion due to increased urinary magnesium excretion. Urinary calcium decreased during vitamin B-6 depletion and increased as dietary vitamin B-6 increased. Urinary oxalate was significantly higher at the end than at the beginning of vitamin B-6 depletion and was higher with plant than animal protein diets. The results suggest that vitamin B-6 depletion may alter calcium and magnesium metabolism and that dietary components associated with the protein source may influence calcium retention. PMID- 1415011 TI - Sex differences in postabsorptive plasma vitamin A transport. AB - This study examined postabsorptive plasma vitamin A after doses of retinyl palmitate in healthy men (n = 28) and women (n = 31). On consecutive days one physiologic [3000 retinol equivalents (RE)] and one pharmacologic dose (105,000 RE) were administered and blood samples collected. Plasma retinol and retinyl esters were measured by HPLC. Tolerance curves were constructed by plotting plasma retinyl ester concentration vs time. Postprandial retinyl ester response was measured as peak rise in retinyl ester concentration and area under the curve (AUC). Peak plasma retinyl ester concentration occurred earlier for females but the earlier peak was significant only for younger subjects (< or = 50 y, P < 0.02) given the low dose and older subjects (> 50 y, P < 0.02) given the high dose. Peak rise and AUC were lower in females than in males, but this difference was significant for the high dose only (P < 0.05). In the high-dose experiment, when each age group was evaluated for sex differences the peak rise was significantly greater in males than in females in the older subjects (P < 0.05). Postabsorptive plasma retinol did not change from fasting concentrations. A lower plasma response in retinyl esters in women could be due to a more efficient chylomicron-remnant clearance. PMID- 1415012 TI - Interactions among dietary manganese, heme iron, and nonheme iron in women. AB - The relationship among dietary intake of heme iron, nonheme iron, and manganese on indexes of hematological and nutritional status in regard to manganese of 47 women consuming their typical diets was investigated. Increasing dietary iron intake, by consuming more nonheme iron in the diet, had questionable effects on hematological status (hematocrit values and ferritin and transferrin concentrations) and negative effects on nutritional status in regard to manganese (serum manganese, urine manganese, and lymphocyte manganese-dependent superoxide dismutase activity). In contrast, heme-iron intake was positively correlated with hematological status and had no consistent effect on nutritional status in regard to manganese. Differences in dietary manganese intake had no consistent effect on indices of manganese or iron status, possibly because foods that contain significant amounts of manganese (green vegetables, breads, and cereals) often contain significant amounts of nonheme iron. Thus, increasing dietary manganese intake by consuming these foods is apt to have limited impact on manganese status because of the interaction between nonheme iron and manganese. PMID- 1415013 TI - Selenium status in patients with Crohn's disease. AB - Twenty-seven of 66 patients with Crohn's disease had reduced concentrations of selenium and glutathione peroxidase in plasma and erythrocytes. When the patients were subgrouped according to the length of resected small bowel, a significant reduction of selenium and glutathione peroxidase in both plasma and erythrocytes was only found in patients with a resection > 200 cm. A highly significant correlation between selenium and glutathione peroxidase was found in plasma (r = 0.81) as well as in erythrocytes (r = 0.62), but no correlation was observed in the control group. A statistically significant correlation was also found between plasma selenium and the Harvey-Bradshaw score (r = -0.44), body mass index (wt/ht2) (r = 0.47), and plasma albumin (r = 0.29). Patients with a small-bowel resection > 200 cm appear to be at risk of developing severe selenium deficiency. These patients should have their selenium status monitored and probably receive selenium supplementation. PMID- 1415014 TI - Diet, prolactin, and breast cancer. AB - Relationships between dietary nutrients and plasma prolactin concentration were studied in 249 women with a history of nonskin cancers among first-degree female relatives. For each quintile of nutrient density, the odds ratio (OR), relative to the lowest quintile, of having an elevated (above the median) prolactin concentration was estimated by logistic regression, taking into account parity, menopausal status, and current tobacco-smoking habits. For nutrient densities estimated from 24-h recall data there was a significant positive association between plasma prolactin concentration and increasing saturated fatty acid intake; the OR of elevated prolactin in the top quintile was 3.1 [95% confidence interval (CI) 1.2-8.1] and there was a negative association with vitamin C [OR in the top quintile 0.28, (95% CI 0.10-0.78)]. For usual nutrient densities (estimated by quantitative food frequency questionnaire) there was a statistically significant trend (P = 0.04) toward lower prolactin concentrations with increasing sodium density, and a marginally significant positive trend (P = 0.07) with increasing dietary density of refined sugars. PMID- 1415015 TI - Nutritional status of infants with cystic fibrosis. PMID- 1415016 TI - Iodine and selenium deficiency in northern Zaire. PMID- 1415017 TI - Glutamine and nitrogen balance. PMID- 1415018 TI - Nutrition training in graduate medical education. PMID- 1415019 TI - Composite B-cell and T-cell lymphoma. Coincidental occurrence or related neoplasms? PMID- 1415020 TI - Anti-phospholipid antibodies. PMID- 1415021 TI - Histologic changes in liver biopsy specimens produced by recombinant interferon alpha-2b therapy for chronic non-A,non-B viral hepatitis. A randomized controlled trial. AB - The effects of interferon therapy on liver histologic findings were assessed in a randomized controlled trial consisting of 80 patients with chronic non-A,non-B hepatitis. Twenty-eight patients received 1 million units of recombinant interferon alpha-2b; 25 patients received 3 million units, subcutaneously, three times a week for 24 weeks; and 21 patients were observed as untreated controls; all of them underwent liver biopsy within 6 months from the beginning of the study and on the last day of therapy. Six patients were withdrawn from the study because of inadequate liver biopsy specimens. Alanine aminotransferase levels were determined before, during, and after therapy. For each biopsy, a semiquantitative score of histologic features, the histologic activity index, and the overall histologic assessment were performed. Ninety-five percent of patients tested positive for hepatitis C virus antibody. Portal inflammation, piecemeal and spotty necrosis, and bile duct proliferation were significantly decreased in patients with normalized alanine aminotransferase. The effectiveness of therapy was dose dependent: piecemeal and spotty necrosis and the histologic activity index showed a significant decrease only in 3-million-unit-treated patients. Hepatocellular degeneration and fibrosis did not change significantly after treatment. PMID- 1415022 TI - Histologic changes in Chinese patients with chronic hepatitis B virus infection after interferon-alpha therapy. AB - To evaluate the histologic effects of interferon-alpha (IFN alpha) therapy on chronic hepatitis B virus (HBV) infection, a semiquantitative study using a modified Knodell's numeric histologic scoring system was performed on paired pre- and post-treatment liver biopsy specimens from 127 adult Chinese patients from two trials of IFN alpha therapy (IFN alpha, n = 86; control, n = 41). The effects of IFN alpha therapy on the hepatic expression of HBV antigens were also determined using immunohistochemical analysis. Serologic response with clearance of HBV e antigen (n = 18) was associated with reduction in lobular activity, periportal piecemeal necrosis, portal inflammation, and total histologic scores. Loss of HBV e antigen also was associated with a reduction in the amount of HBV core antigen in the hepatocytes. In contrast, there was an increase in hepatic expression of HBV surface antigen after IFN alpha therapy. Patients who lost HBV e antigen with IFN alpha therapy were characterized by more severe initial periportal piecemeal necrosis before treatment. These data indicate that (1) serologic response is associated with a reduction in hepatic HBV replication and an improvement in hepatic histology, and (2) patients with severe periportal piecemeal necrosis respond more favorably to IFN alpha therapy. PMID- 1415024 TI - Clinical significance of immunoglobulin A versus immunoglobulins G and M anti cardiolipin antibodies in patients with systemic lupus erythematosus. Correlation with thrombosis, thrombocytopenia, and recurrent abortion. AB - Serum levels of immunoglobulins (Ig) A, G, and M anti-cardiolipin (aCL) antibodies were determined by enzyme-linked immunosorbent assay in a group of selected systemic lupus erythematosus female patients. Patients were divided into three groups based on their clinical history of thrombosis with or without thrombocytopenia (group I), thrombocytopenia alone (group II), and neither of these (group III). After the aCL antibody levels were determined, the patients' obstetric histories of pregnancies and abortions were reviewed. A high incidence of one or more abortions was seen only in group I patients. A high prevalence of elevated levels of IgA and IgG (but not IgM) aCL antibodies was observed in group I patients. However, among the patients in group II, only the levels of IgA aCL antibodies were increased. In both groups, the addition of the IgA aCL determination--to the classical IgG and IgM aCL assays--increased the prevalence of positive reactors in 31.6%. These results indicate that high levels of IgA aCL antibodies correlated better with thrombocytopenia than either IgG or IgM. Also, the importance of including the determination of IgA aCL antibodies to assess properly the risk of thrombosis, thrombocytopenia, and recurrent abortions in systemic lupus erythematosus patients is demonstrated. PMID- 1415023 TI - The use of monoclonal antibodies against primary myeloid granules in normal and leukemic cells. AB - Three monoclonal antibodies, K101, D46, and H36/71 (CD15), reactive with membrane components of primary granules of human promyelocytes, were studied to assess their binding to normal and leukemic cells. Using the alkaline phosphatase antialkaline phosphatase technique, these antibodies were applied to sections of normal organs and to peripheral blood and bone marrow films from hematologically normal individuals and patients with hematologic malignancies. In control experiments, antibodies showed reactivity with cytoplasmic constituents of granulocytes from the promyelocytic to the neutrophilic stage. In acute myeloid leukemia, antibody K101 was positive (more than 20% of blasts) in 13 of 21 (62%) cases, while antibody D46 was positive in 11 of 17 (65%) cases. Antibody H36/71 was positive in only 4 of 24 (17%) cases of acute myeloid leukemia. At least one marker was present in 6 of 8 (75%) cases of acute lymphoblastic leukemia with myeloid antigen-positive blasts and was negative in 20 cases of acute lymphoblastic leukemia with myeloid antigen-negative blasts. These results support the view that abnormal granules (with defective expression of the D46, K101, and H36/71 antigens) form in blastic and leukemic cells of patients with acute myeloid leukemia. Data also suggest that membrane components of myeloid granules are made in the cytoplasm of cells from some acute lymphoblastic leukemia patients with myeloid antigen-positive blasts. PMID- 1415025 TI - Platelet membrane glycoproteins. Functional characterization and clinical applications. PMID- 1415026 TI - Duodenal biopsy specimens in HIV-infected patients. PMID- 1415027 TI - Duodenal biopsy specimens in HIV-infected patients. PMID- 1415028 TI - Duodenal biopsy specimens in HIV-infected patients. PMID- 1415029 TI - Risk factors for drug use in urban adolescents: identification and cross validation. AB - Examined the relationship between 26 dichotomous risk factors and drug use in derivation (N = 1,352) and cross-validation (N = 1,309) samples of seventh graders in the public school system of a large southeastern city. The majority of students was African American, many came from low-income, single parent families. A total of 20 risk factors representing a variety of variables was significantly related to at least one category of drug use in both samples. Regression analyses identified a subset of 11 risk factors with minimum overlap. The simple sum of these 11 risk factors was significantly associated with prevalence of use for cigarettes, beer and wine, hard liquor, marijuana, and other drugs. The total number of risk factors also showed a curvilinear relationship with the frequency of 30-day use for each category of drug. Theoretical and practical implications of these findings are discussed. PMID- 1415030 TI - An advocacy intervention program for women with abusive partners: initial evaluation. AB - Experimentally tested the hypotheses that (1) battered women are in need of numerous community resources upon exit from a domestic violence shelter, (2) working with advocates increases women's effectiveness in obtaining needed resources and social support, and (3) success in obtaining resources and social support increases women's levels of life satisfaction and decreases their risk of further abuse. The initial findings of a short-term intervention project designed to provide postshelter advocacy services to women with abusive partners are presented. One-hundred forty-one battered women were interviewed immediately upon their exit from a domestic violence shelter as well as 10 weeks thereafter. Half the sample was randomly assigned to receive the services of trained advocates who assisted them in accessing needed community resources. Women who worked with advocates reported being more effective in accessing resources and had higher levels of social support and overall quality of life postintervention. Although all women reported some decrease in postshelter abuse, there were no differences between those with and those without advocates, and abuse continued to be a problem for many women. PMID- 1415031 TI - The relation of peer social support and psychological symptomatology during the transition to junior high school: a two-year longitudinal analysis. AB - Studied the longitudinal relation of peer social support and psychological symptomatology among a sample of 143 early adolescents during a two-year period spanning the transition from elementary school to junior high school. Correlational analyses indicated strong inverse relations between peer support and symptoms, both cross sectionally and across time. Prospective analyses investigated the degree to which prior levels of peer support were related to subsequent symptoms after controlling for initial levels of symptoms and, conversely, the degree to which prior symptoms were related to future levels of peer support after controlling for initial levels of support. A significant prospective effect for peer support was found only for the specific period encompassing the school change. Prospective effects for symptoms were more numerous and of longer duration. The discussion emphasizes how the relation among support, stress, and mental health may differ over the course of a major life transition. Implications are also considered for the timing of preventive interventions. PMID- 1415032 TI - The role of life events, family support, and competence in adolescent substance use: a test of vulnerability and protective factors. AB - Tested propositions from a model of vulnerability and protective factors with a multiethnic sample of 1,289 urban adolescents, aged 11-13 years. The criterion variable was a composite score for cigarette, alcohol, and marijuana use. Multiple regression analyses indicated that vulnerability factors (negative life events, negative affect) were related to a higher level of substance use, and protective factors (parent emotional and instrumental support, academic and adult competence, positive affect) were related to a lower level of substance use; peer competence was positively related to substance use in a multivariate model. There was a significant overall interaction of Vulnerability x Protective Factors, consistent with a stress-buffering effect. Individual interactions for Life Events x Family Support, Life Events x Competence, and Negative x Positive Affect also were consistent with buffering effects. Implications for theories of substance use and primary prevention are discussed. PMID- 1415033 TI - Social support in chumships and adjustment in children of divorce. AB - Examined the relations between support from intimate friends or "chums" and stress, age, and gender in predicting psychological adjustment using a sample of 117 8- to 15-year old children who had experienced parental divorce. Both parents and children provided information on children's adjustment. In predicting children's reports of their adjustment, the direct effect of chum support was found to be moderated by children's age. In predicting parental reports of children's adjustment, no significant main effects or interaction effects occurred. The findings are discussed with attention to the divergent perspectives of different reporters. PMID- 1415034 TI - Coaches: a missing link in the health care system. PMID- 1415035 TI - Water intoxication: a problem of bottle-feeding. PMID- 1415036 TI - Low vitamin A during measles. PMID- 1415037 TI - Oxygen saturation in newborns at altitude. PMID- 1415038 TI - 'Hey, nice sundamage!'. PMID- 1415039 TI - Immunogenicity and reactogenicity of Takeda acellular pertussis-component diphtheria-tetanus-pertussis vaccine in 2- and 3-month-old children in Japan. AB - OBJECTIVE: To compare the reactogenicity and immune response to the Takeda acellular pertussis-component diphtheria-tetanus-pertussis (APDT) vaccine in children when immunization commenced at 2 months (group A) vs 3 months (group B) of age. DESIGN: Longitudinal, nonblinded, comparative study. SETTING: Pediatric well-child clinics. PARTICIPANTS: Healthy 50- to 98-day-old infants. RESULTS: Good antibody responses to lymphocytosis-promoting factor, filamentous hemagglutinin, agglutinogens, and pertactin occurred in both age groups after both the third and fourth vaccine doses. Both young age and transplacentally acquired maternal antibody independently and together have a suppressive effect on the response to the four antigens in this APDT vaccine. However, these effects appear to be minor. Vaccine reactions were mild; group A children had slightly but not significantly higher rates than group B children. CONCLUSION: The present US diphtheria and tetanus toxoids and pertussis vaccine immunization schedule should also be satisfactory with this acellular pertussis component vaccine. PMID- 1415040 TI - The agglutinin response to whole-cell and acellular pertussis vaccines is Bordetella pertussis--strain dependent. AB - OBJECTIVE: To determine the significance of the Bordetella pertussis strain used as the antigen in the agglutinin assay for the evaluation of pertussis vaccines. DESIGN: Randomized, double-blind study. SETTING: Health maintenance organization clinics, primary care clinic at a referral hospital, and private practices in Los Angeles County, California. PARTICIPANTS: Forty healthy infants. SELECTION PROCEDURES: Convenience sample. INTERVENTIONS: Twenty infants received whole-cell pertussis-component diphtheria-tetanus-pertussis vaccine (DTP), and 70 infants received acellular pertussis-component diphtheria-tetanus-pertussis vaccine (APDT) at ages 2, 4, and 6 months. MEASUREMENTS: The agglutinin assay was performed using three separate B pertussis strain preparations: (1) strains 130 and 138 in equal quantities, the constituents of the DTP vaccine, (2) strain 460, and (3) strain Tohama, the constituent of the APDT vaccine. RESULTS: The agglutinin titers were highly strain dependent; in both groups of vaccinees at both ages the Tohama values were highest, followed by strain 460 and then strains 130/138. The vaccine groups had comparable titers at age 2 months regardless of the assay antigen used. However, at age 7 months, after three immunizations, the DTP group geometric mean titer was more than 10 times greater than that of the ADPT group using strains 130/138, but only 2.6 times higher using strain 460 and almost equivalent using Tohama strain. CONCLUSION: Vaccine group agglutinin value comparisons strongly depend on assay antigens used. PMID- 1415041 TI - Confirmation. Practice behavior for treatment of new morbidity disorders reflects residency experience. AB - The purpose of the present study was to evaluate congruence between practice and residency training in the treatment of children with five "new morbidity" disorders. Data were obtained through mailed questionnaires. Counseling and behavior modification, without medications, were used for all five disorders by respondents most recently completing pediatric residency. Medications were used more frequently by pediatricians who had completed their residency training longer ago, particularly for nocturnal enuresis and chronic abdominal pain. The most recent graduates tended to treat a larger number of children with temper tantrums and separation anxiety. This is believed to result from more recent graduates being more comfortable and confident in recognizing and treating these conditions. In contrast, no association was noted between year in which residency was completed and number of children treated for nocturnal enuresis and chronic abdominal pain. This results from parents volunteering these symptomatic conditions since they perceive them to be medical problems. PMID- 1415042 TI - Uses and technique of pediatric lumbar puncture. AB - OBJECTIVES: To review diagnostic and therapeutic indications, contraindications, complications, and technique of pediatric lumbar puncture with emphasis on diagnosis of bacterial meningitis in bacteremia, cellulitis, and fever with seizures and to discuss cerebrospinal fluid findings in partially treated infection and traumatic blood-contaminated spinal tap. RESEARCH DESIGN: Literature review. CONCLUSIONS: We recommend lumbar puncture for children younger than 1 year with bacteremia, children with Haemophilus influenzae type B cellulitis, and children with fever and seizures not classified as simple. Pretreatment with antibiotics rarely changes cerebrospinal fluid characteristics such that a diagnosis of bacterial meningitis would be obscured. In a traumatic spinal tap, the equation to predict cerebrospinal fluid pleocytosis based on the peripheral blood cell count is invalid. When used together, cerebrospinal fluid glucose level, Gram's staining, and observed-to-expected ratio of white blood cells are highly reliable in diagnosing bacterial meningitis. PMID- 1415043 TI - Pediatric tuberculosis and human immunodeficiency virus infection in Palm Beach County, Florida. AB - OBJECTIVE: To describe the factors underlying an increasing incidence of tuberculosis in children. DESIGN: Descriptive case review. SETTING: Palm Beach County, Fla. PARTICIPANTS: Forty-four children with suspected and confirmed pediatric tuberculosis from 1985 through 1989. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: From 1988 through 1989, tuberculosis was confirmed in 15 children and suspected in another 16 compared with data from 1985 through 1987 in which the disease was confirmed in nine children and suspected in four. Pediatric tuberculosis occurred primarily in blacks younger than 5 years; the increase in the number of cases reported in 1988 and 1989 occurred only in blacks. One child in whom tuberculosis was confirmed during the recent period was infected with the human immunodeficiency virus (HIV); however, among children with suspected tuberculosis, four of the nine children tested were seropositive for HIV. There was no evidence of increased transmission of tuberculosis to children by HIV-seropositive adults compared with transmission by HIV seronegative adults with TB. New adult tuberculosis cases in the county increased annually, from 92 cases in 1986 to 169 in 1989, of whom at least 36% were infected with HIV. CONCLUSIONS: The largest effect of the HIV epidemic on tuberculosis in children appeared to be indirect, through an increase in the number of adults with active tuberculosis serving as potential sources of tuberculosis infection for children. A direct effect of HIV infection in the progression of tuberculous disease in children is likely, but was not detected in this investigation. Case-finding for tuberculosis among children will need to increase, particularly in areas heavily affected by acquired immunodeficiency syndrome, but may be complicated by the difficulty of diagnosing tuberculosis in HIV-infected children. PMID- 1415044 TI - IgM antibody to Treponema pallidum in cerebrospinal fluid of infants with congenital syphilis. AB - OBJECTIVES: To characterize the neonatal IgG and IgM response to specific Treponema pallidum antigens in the cerebrospinal fluid (CSF) of infants with congenital syphilis. DESIGN: Cross-sectional survey. SETTING: Newborn nursery and neonatal intensive care unit of a county hospital in Dallas, Tex. PARTICIPANTS: Twenty-one infants born to mothers with reactive serologic tests for syphilis were enrolled. Group 1 consisted of six infants with clinical and laboratory evidence of congenital syphilis; group 2, six asymptomatic infants born to mothers with untreated syphilis; and group 3, nine asymptomatic infants whose mothers were treated for syphilis before delivery. SELECTION PROCEDURES: Random sample. MEASUREMENTS AND RESULTS: Immunoblotting was used to examine the IgM and IgG reactivities of neonatal serum and CSF against T pallidum antigens. Among serum samples of all group 1 infants, a specific IgM response to T pallidum antigens with apparent molecular masses of 47, 45, and 17 kd was observed. Cerebrospinal fluid IgM reactivity to a 47-kd antigen of T pallidum was seen in four group 1 infants. Serum samples from two group 2 and three group 3 infants demonstrated IgM reactivity against the 47-kd antigen and, in some cases, against the 45-kd antigen of T pallidum. None of 15 group 2 and 3 infants had a positive CSF IgM immunoblot result. The IgG reactivity in CSF was similar in the three groups and was directed against T pallidum antigens with apparent molecular masses of 72, 59, 47, 45, 42, 37, 34, 17, and 15 kd. CONCLUSIONS: A specific IgM response to T pallidum antigens, particularly the 47-kd antigen, was detected in the CSF of some infants with clinical and laboratory evidence of congenital syphilis. The potential usefulness of this test for the diagnosis of congenital neurosyphilis merits further study. PMID- 1415045 TI - The natural history of direct hyperbilirubinemia associated with extracorporeal membrane oxygenation. AB - OBJECTIVE: To determine the incidence and natural history of direct hyperbilirubinemia in neonates treated with extracorporeal membrane oxygenation. DESIGN: A prospective series of patients. SETTING: A level 3 neonatal intensive care unit and center for extracorporeal membrane oxygenation in Ohio. PARTICIPANTS: Sixty-seven consecutive patients treated with extracorporeal membrane oxygenation in 33 months. INTERVENTION: None. MEASUREMENTS/RESULTS: Twenty-six (39%) developed direct hyperbilirubinemia. In 14 (54%), bilirubin levels were mildly elevated and occurred only during extracorporeal membrane oxygenation therapy. Levels were more severely elevated in the remaining 12 patients (46 +/- 10 mumol/L [2.7 +/- 0.6 mg/dL] vs 159 +/- 101 mumol/L [9.3 +/- 5.9 mg/dL], P less than .0001). Duration and severity of hyperbilirubinemia were correlated. Hyperbilirubinemia resolved in all patients by 9 weeks after extracorporeal membrane oxygenation therapy. No structural abnormalities or infectious agents were identified as causes. Aluminum levels were evaluated for 40 patients, were not in the toxic range, and did not correlate with hyperbilirubinemia. Multiple linear regression analysis suggested that hyperbilirubinemia in these cases resulted from interaction of injuries, with the primary contributor being hemolysis during extracorporeal membrane oxygenation. CONCLUSIONS: Direct hyperbilirubinemia occurs frequently in patients treated with extracorporeal membrane oxygenation and may be severe. However, direct hyperbilirubinemia typically resolves without short-term sequelae. Hemolysis may be an important contributing factor. PMID- 1415046 TI - The accuracy of antenatal ultrasonography in identifying renal abnormalities. AB - OBJECTIVE: To determine the accuracy of measuring antenatal renal pelvic diameter for prediction of renal abnormalities. RESEARCH DESIGN: Prospective evaluation of all pregnant women undergoing ultrasonography. SETTING: A teaching hospital providing primary and referral maternity care. PARTICIPANTS: Fifty-six pregnant women with suspected fetal hydronephrosis or cystic lesions identified from 7500 ultrasonograms over 3 years. METHODS: Antenatal renal pelvic diameter was measured in the anteroposterior dimension. Neonates underwent postnatal ultrasonography after day 3 of life; if the results were abnormal, a cystogram and renal diuretic scan were obtained. RESULTS: None of 50 kidneys 15 mm or smaller in anteroposterior pelvic diameter had obstruction; 11 (79%) of 14 kidneys larger than 15 mm were obstructed or demonstrated vesicoureteral reflux. Of 12 kidneys believed to be multicystic before birth, five (42%) proved to have hydronephrosis. CONCLUSIONS: Since the majority of fetuses with suspected hydronephrosis proved to be normal, parents should not be unduly alarmed by the physician. Renal pelvic diameter of more than 15 mm is strongly predictive of hydronephrosis. Since severe hydronephrosis is treatable and can be mistaken for a multicystic kidney antenatally, full radiologic evaluation is needed soon after birth. PMID- 1415047 TI - Sexual abuse of human immunodeficiency virus-positive children. Outcomes for perpetrators and evaluation of other household children. AB - OBJECTIVE: To obtain the following data that pertain to programs for the prevention of sexual abuse and sexual transmission of human immunodeficiency virus (HIV) to children: (1) to determine the prevalence of sexual abuse among siblings and other children cohabiting with sexually abused HIV-positive children, and (2) to determine if programs designed to restrain identified perpetrators from further acts of child sexual abuse were instituted. DESIGN: Case series. SETTING: Households of previously described sexually abused HIV infected children. PATIENTS AND OTHER PARTICIPANTS: Twenty-two siblings or other children who lived in the homes of 14 previously described HIV-infected sexually abused children. Eight perpetrators of the abuse were identified. MAIN OUTCOME MEASURES: Sexual abuse of cohabiting children was confirmed with disclosure interviews, witness by other persons, diagnosis of another sexually transmitted disease, or an abnormal physical examination result that was highly suggestive of sexual abuse. Telephone contact with the Department of Social Services, county sheriff or police, and district attorney provided data regarding reports, criminal indictments, trials, convictions, and plea-bargain arrangements for the identified perpetrators. RESULTS: Eleven (50%) of the 22 cohabiting children were confirmed to have been sexually abused and four (18%) were suspected of having been sexually abused. Seven (32%) of the cohabiting children could not be examined and it was not known if they had been sexually abused. No assailant was tried for a criminal offense, required to participate in offender therapy, or prohibited from unsupervised visitation of children. CONCLUSION: Programs for the prevention of sexual abuse and sexual transmission of HIV to children require means of ensuring the safety of children exposed to perpetrators and require adequate supervision of perpetrators and their adherence to therapy. PMID- 1415048 TI - The clinical spectrum of chronic appendiceal abscess in cystic fibrosis. AB - OBJECTIVE: To describe the varied characteristics seen in patients with cystic fibrosis who develop chronic abscess formation secondary to unrecognized appendicitis. DESIGN: Patient series. SETTING: Cystic Fibrosis Care Centers in Columbus, Ohio, and Tucson, Ariz. PARTICIPANTS: Five patients with cystic fibrosis who developed chronic abdominal abscesses secondary to occult appendicitis are described. Two patients developed fistula formation with purulent fluid drainage before diagnosis. One patient developed an extensive psoas abscess. Another presented with prolonged fever of unknown origin. These patients were identified by retrospective review of the past 20-year experience at two Cystic Fibrosis Care Centers. CONCLUSIONS: Development of chronic abdominal abscess related to unrecognized appendicitis is a rare but important complication in patients with cystic fibrosis. Prompt diagnosis depends on physician familiarity with the varied presentations of this entity. Diagnostic abdominal computed tomography and/or ultrasonography should particularly be considered when patients with cystic fibrosis present with pain, mass, or drainage from the right flank; prolonged fever; a limp; or failure of suspected meconium ileus equivalent syndrome to respond promptly to cathartic measures. PMID- 1415049 TI - Trends in anthropometric measurements among Mescalero Apache Indian preschool children. 1968 through 1988. AB - OBJECTIVE: To determine if there were trends in underweight, short stature, and obesity among 1- through 5-year-old Mescalero (NM) Apache Indian children from 1968 through 1988. DESIGN: Cross-sectional review of hospital clinic charts for five cohorts. SETTING: General pediatric outpatient clinic at the Mescalero Indian Health Service Hospital. PARTICIPANTS: Sixty-nine patients aged 1 through 5 years in 1968, 1973, 1978, 1983, or 1988 for whom weight and height were recorded during a well-child visit that occurred in the respective year. SELECTION PROCEDURES: Approximately half the charts were screened for eligibility through systematic sampling for all years except 1988; for 1988 all available charts were screened for eligibility for the study. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We found trends of decreasing prevalence of both underweight (defined as weight-for-height below the fifth percentile) and short stature (defined as height-for-age below the fifth percentile) based on the Centers for Disease Control/World Health Organization growth reference. We found no secular trends in obesity (weight-for-height above the 95th percentile), although the prevalences throughout the 21-year period were as much as two to four times higher than expected when compared with the Centers for Disease Control/World Health Organization reference. There has been an upward shift in both weight-for-height and height-for-age distributions since 1968, indicating that Mescalero children today are, on average, heavier and taller. CONCLUSIONS: Underweight and short stature decreased among Mescalero preschool children from 1968 through 1988, suggesting nutritional improvements. However, given the current high prevalence of obesity, it is recommended that surveillance of nutritional status be continued and appropriate interventions be developed to treat and prevent obesity in this population. PMID- 1415050 TI - Radiological cases of the month. Osteogenic sarcoma as a second malignant neoplasm in a child with retinoblastoma. PMID- 1415051 TI - Picture of the month. Neonatal herpes simplex infections. PMID- 1415052 TI - Pathological case of the month. Rabies. PMID- 1415053 TI - Musculoskeletal aspects of prune-belly syndrome. Description and pathogenesis. AB - OBJECTIVE: To determine the types and prevalence of musculoskeletal involvement in children with prune-belly syndrome, and to analyze the pathogenesis of the syndrome in relationship to the musculoskeletal deformities. DESIGN: A retrospective review of charts and roentgenograms along with a comprehensive review of 188 cases from the literature. SETTING: Tertiary care children's hospital. PARTICIPANTS: Twelve boys treated between 1975 and 1990. MEASUREMENTS/MAIN RESULTS: The prevalence of musculoskeletal involvement in patients was 45%. The involvement can be congenital (eg, clubfeet, limb deficiencies, teratologic hip dysplasia, and vertebral malformations) or developmental (eg, renal osteodystrophy, scoliosis, and pectus excavatum and/or pectus carinatum). The embryologic characteristics of congenital musculoskeletal problems correlate better with the embryologic theory of the prune-belly syndrome (an aberration of mesenchymal development around 6 weeks of gestation) than with the distal urinary tract obstructive theory. CONCLUSION: Since children with prune-belly syndrome are now living into adulthood, these musculoskeletal aspects will become important regarding potential morbidity. PMID- 1415054 TI - Usefulness of serum apolipoprotein B levels for screening children with primary dyslipoproteinemias. AB - OBJECTIVE: To assess the use of serum apolipoprotein B levels for screening children with primary dyslipoproteinemia (those with elevated levels of low density lipoprotein cholesterol [LDL-C]) and to know the types of dyslipoproteinemias we can identify. DESIGN: Criterion standard. SETTING: Referral center. PARTICIPANTS: We have studied 267 children. Of these, 31 had parents with dyslipoproteinemia, 38 had parents with ischemic heart disease, and 43 had hypercholesterolemia detected by routine analyses. One hundred fifty-five were considered healthy children and comprised the control group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sensitivity was 87% for total serum cholesterol levels and 73% for serum apolipoprotein B levels. Of the children studied, 31 had elevated levels of serum LDL-C. The types of dyslipoproteinemia in children with both elevated levels of serum LDL-C and apolipoprotein B consisted of heterozygous familial hypercholesterolemia, found in 12 (50%) of 24 patients; familial combined hyperlipidemia, found in 11 (46%) of 24 patients; and polygenic hypercholesterolemia, found in one (4%) of 24 patients. CONCLUSIONS: Serum apolipoprotein B level appears to be a good tool for screening children with elevated levels of LDL-C and is equivalent to using total serum cholesterol levels. In children with elevated serum LDL-C and apolipoprotein B levels, we can identify not only patients with heterozygous familial hypercholesterolemia but also those with familial combined hyperlipidemia or polygenic hypercholesterolemia. PMID- 1415055 TI - Serum creatinine level and renal function in children. AB - OBJECTIVE: To evaluate the accuracy of serum creatinine and height/serum creatinine glomerular filtration rate (Cr-GFR) formula as screening tests for abnormal renal function defined by plasma diethylenetriaminepenta-acetic acid (DTPA) clearance. DESIGN: Patient series. SETTING: The Children's Hospital of Buffalo (NY). PATIENTS: Eighty-seven consecutive patients ranging in age from 2 to 20 years. MEASUREMENTS: The Cr-GFR was calculated by means of the formula GFR (milliliters per minute per 1.73 m2) = kL/serum creatinine (milligrams per deciliter), where L is body length in centimeters and k is a constant dependent on age and sex. Plasma clearance of technetium Tc 99m-labeled DTPA was our reference method for determination of GFR (DTPA-GFR). RESULTS: The Cr-GFR formula identified children with impaired renal function (DTPA clearance, less than 80 mL/min per 1.73 m2) with a sensitivity of 95% and a specificity of 93%. In contrast, the sensitivity and specificity of elevated serum creatinine level for this purpose were 80% and 96%, respectively. Of the children with renal insufficiency (DTPA clearance, 40 to 79 mL/min per 1.73 m2), 91% were correctly identified by the Cr-GFR formula. However, only 65% of these children had elevated serum creatinine levels. Although all children with renal failure (DTPA clearance, less than 40 mL/min per 1.73 m2) had abnormally high serum creatinine levels, the specificity of this test was significantly lower than that of the Cr GFR formula (75% vs 100%, respectively). CONCLUSIONS: The Cr-GFR formula is superior to serum creatinine level for estimating GFR. This formula provides a simple, reasonably accurate screening test for the presence and severity of impaired renal function. PMID- 1415056 TI - Benign neonatal sleep myoclonus. A differential diagnosis of neonatal seizures. AB - OBJECTIVE: To describe 10 infants with benign neonatal sleep myoclonus. DESIGN: Patient series, representing the experience of one pediatric neurologist. SETTING: Referral-based Pediatric Neurology Service at a Children's Hospital. PATIENTS: Sequential sample of 10 neonates referred for assessment of seizures and found to have benign neonatal sleep myoclonus. Neonates who did not have the events of concern during electroencephalography or in whom electroencephalography was not done were excluded even if the clinical features suggested the entity. RESULTS: Our patients met the criteria for the diagnosis. The myoclonus often increased with gentle restraint. The amplitude and duration of events mimicked convulsive status epilepticus and serial seizures in four neonates. In two of them the myoclonus worsened in spite of anticonvulsant therapy, decreasing substantially when such treatment was stopped. CONCLUSION: Benign neonatal sleep myoclonus, an entity characterized by (1) neonatal onset, (2) myoclonic jerks only during sleep, (3) abrupt and consistent cessation with arousal, (4) absence of concomitant electrographic changes suggestive of seizures, and (5) good outcome must be included in the differential diagnosis of neonatal seizures. PMID- 1415057 TI - Lead encephalopathy in Saudi Arabian children. PMID- 1415058 TI - Lead poisoning in young children in Washington, DC: a crisis that remains to be addressed. PMID- 1415059 TI - Another look at pediatrician promotion of breast-feeding. PMID- 1415060 TI - Cognition and tyrosine supplementation among school-aged children with phenylketonuria. PMID- 1415061 TI - Health effects of lead at low exposure levels. Expert consensus and rationale for lowering the definition of childhood lead poisoning. PMID- 1415062 TI - Meconium aspiration. PMID- 1415063 TI - Management of a piglet model of the meconium aspiration syndrome with high frequency or conventional ventilation. AB - OBJECTIVE: To assess the usefulness of three methods of high-frequency ventilation in the early management of a piglet model of the meconium aspiration syndrome. DESIGN: Randomized, block design. SETTING: Animal research facility. SUBJECTS: Fifty-six mixed-breed newborn piglets aged 1 to 4 days and weighing 1.8 to 2.7 kg. INTERVENTIONS: After instillation of a 2.2-mL/kg solution of 25% meconium, 56 piglets were randomized to receive treatment with (1) a conventional positive-pressure infant ventilator, (2) the Bunnell Life Pulse high-frequency jet ventilator, (3) the Bird model VDR high-frequency flow interruptor, or (4) the Infant Star high-frequency flow interruptor. We adjusted ventilator settings to maintain partial pressures of arterial oxygen (PaO2) of 80 to 120 cm H2O and partial pressures of arterial carbon dioxide (PaCO2) of 30 to 50 cm H2O during the 6 hours of ventilation. MEASUREMENTS AND MAIN RESULTS: We compared pulmonary histologic alterations and four physiologic parameters: (1) mean airway pressure, (2) PaCO2, (3) ratio of PaO2 to partial alveolar oxygen pressure (PAO2), and (4) oxygenation index ([(fraction of inspired oxygen)(mean airway pressure)(100)]/PaO2). The two measures of oxygenation were similar for all four devices except at 4 hours, when the PaO2/PAO2 ratio on positive-pressure ventilation was significantly higher than that on high-frequency jet ventilation (P = .008). The histologic changes on positive-pressure ventilation (atelectasis, inflammation, presence of meconium, and exudative debris) were significantly worse than those on high-frequency jet ventilation or flow interruption (P < .0001). CONCLUSIONS: The finding of less severe pathologic alterations with various types of high-frequency ventilators justifies further investigations into the management of the meconium aspiration syndrome with these devices. PMID- 1415064 TI - Retinal hemorrhages in newborn piglets following cardiopulmonary resuscitation. AB - OBJECTIVE: To determine whether conventional cardiopulmonary resuscitation causes retinal hemorrhages in piglets. DESIGN: Nonrandomized observations. SETTING: Animal physiology laboratory. PARTICIPANTS: Six 3.5- to 4.5-kg piglets. INTERVENTIONS: Fifty minutes of conventional, closed chest cardiopulmonary resuscitation. MEASUREMENTS/MAIN RESULTS: Intrathoracic venous pressure (right atrium) and intracranial venous pressure (sagittal sinus) were directly measured. At 5 minutes of cardiopulmonary resuscitation, the mean (+/- SEM) sagittal sinus pressure was 41 +/- 8 mm Hg and the mean right atrial pressure was 58 +/- 9 mm Hg. The pressures were sustained throughout the 50 minutes of cardiopulmonary resuscitation. At autopsy, there was no gross or microscopic evidence of retinal hemorrhages. CONCLUSION: These results support the conclusion that cardiopulmonary resuscitation does not cause retinal hemorrhages. PMID- 1415065 TI - Late-onset meningitis in sick, very-low-birth-weight infants. Clinical and sonographic observations. AB - OBJECTIVES: To determine the clinical and sonographic features of late-onset meningitis (after 7 days of life) in sick, very-low-birth-weight infants. DESIGN: Retrospective study of a patient series. SETTING: Neonatal intensive care nursery at Parkland Memorial Hospital in Dallas, Tex. PARTICIPANTS: Ten preterm infants with birth weights of more than 1750 g who developed late-onset meningitis during a 42-month study period. INTERVENTIONS: None. RESULTS: Ten preterm infants developed meningitis at a mean (+/- SD) postnatal age of 20 +/- 14 days. Eight of the infants survived. Initial clinical signs were nonspecific, eg, apnea and bradycardia (eight infants), abdominal distention (five infants), hyponatremia (serum sodium level, < 130 mmol/L), and a decrease in urine output with an increase in weight (three infants). Specific neurologic signs occurred in three infants (seizures [n = 2] and third-nerve palsy [n = 1]). Sonographic abnormalities noted in seven (70%) of the 10 infants included progressive ventriculomegaly (n = 6), thalamic echodensities (n = 3), ventriculitis (n = 4), and cystic leukomalacia (n = 1). The progressive ventriculomegaly developed from 1 to 2 weeks after diagnosis; permanent shunting was required in all six infants. The thalamic echodensities were linear or punctate and developed from 1 to 2 weeks after diagnosis in two infants. CONCLUSIONS: The data indicate the need for a high index of suspicion of meningitis in very-low-birth-weight infants suspected of having sepsis because of the nonspecific clinical presentation of meningitis. Because both progressive ventriculomegaly and thalamic echodensities are late and frequent findings, serial sonograms are essential for careful monitoring of sequelae of disease. PMID- 1415066 TI - Bone mineral metabolism in full-term infants fed human milk, cow milk-based, and soy-based formulas. AB - OBJECTIVE: To study the hypothesis that ingestion of a modified soy-based formula with an improved mineral suspension system may result in bone mineral content similar to that observed in infants fed human milk or cow milk-based formulas. DESIGN: Prospective, self-selected group of infants fed human milk randomized between the two formula-fed groups. SETTING: University-based hospital nursery and follow-up. PARTICIPANTS: Fifty-six normal, healthy, full-term infants, free of major malformations or disorders, including 17 infants fed human milk, 19 infants fed a cow milk-based formula, and 20 infants fed a soy protein formula were followed up to 6 months' postnatal age. The soy-based formula studied was modified to improve the suspendability of the minerals. INTERVENTIONS: Infants were fed human milk or the study formula for the first 4 months, at which time beikost was permitted. Infants fed human milk received vitamin supplementation to provide 400 IU of vitamin D per day. MEASUREMENTS: Anthropometric variables, serum calcium, magnesium, phosphorus, alkaline phosphatase, and parathyroid hormone levels were measured at enrollment, and at 8, 16, and 24 to 26 weeks' postnatal age. Bone mineral content at the distal third radius site was measured with single photon absorptiometry at these times. Growth in the infants did not differ significantly among the groups. There was no significant difference in serum calcium, magnesium, alkaline phosphatase, or parathyroid hormone concentrations among the infants during the study. Serum phosphorus was significantly lower at 8 weeks in the group fed human milk than in that fed the cow milk-based formula. Bone mineral content at 16 and 24 to 26 weeks was higher in the group fed the soy-based formula than in that fed human milk, and bone width was also higher at 16 weeks in the infants fed the soy-based formula. CONCLUSIONS: Improving the suspendability of the mineral system in the soy formula results in bone mineralization in infants fed the soy-based formula similar to that measured in infants fed human milk and cow milk-based formula. We suggest that the suspendability of the minerals used is an important variable in the interpretation of the effect of feedings on the bone mineral status of infants. PMID- 1415067 TI - Radiological case of the month. Autosomal recessive osteopetrosis. PMID- 1415068 TI - Radiological case of the month. Sagittal and lambdoidal craniosynostosis. PMID- 1415069 TI - Picture of the month. Mayer-Rokitansky-Kuster-Hauser syndrome: congenital agenesis of the vagina. PMID- 1415070 TI - Pathological case of the month. Myocardial infarction and coronary Kawasaki-like arteriopathy. PMID- 1415071 TI - Effect of concurrent viral infection on systemic and local antibody responses to live attenuated and enhanced-potency inactivated poliovirus vaccines. AB - OBJECTIVE: To determine the effect of an asymptomatic nonpolioviral infection on the immune response to poliovirus vaccines. DESIGN: Open comparative trial. SETTING: Well-child clinic at The Children's Hospital of Buffalo, NY. PARTICIPANTS: Twenty-seven healthy infants infected with nonpolioviruses and 27 healthy controls matched for age and vaccine group. INTERVENTIONS: Trivalent oral attenuated poliovirus vaccine or enhanced potency inactivated vaccine administered at ages 4 and 12 months. MEASUREMENTS/MAIN RESULTS: Neutralizing antibody to poliovirus serotypes 1, 2, and 3 were determined in the serum and nasopharyngeal secretion samples obtained at ages 4, 5, 12, and 13 months. The IgA antibody titers for polioviruses 1, 2, and 3 were measured in nasopharyngeal secretion samples during the same periods. Antibody responses to poliovirus vaccines were similar in coinfected subjects and healthy controls at ages 5 and 13 months, except for serum neutralizing antibody that was significantly elevated in the controls compared with coinfected subjects (geometric mean [+/- SD] antibody titers, 12.7 +/- 1.6 vs 11.5 +/- 1.7). Concurrent viral infections affected the immune response in recipients of the oral poliovirus vaccine and the enhanced-potency inactivated poliovirus vaccine similarly. The immune response to polioviruses 1 and 3 were more adversely affected by coinfection than was the immune response to poliovirus 2. CONCLUSION: Concurrent asymptomatic viral infections minimally impaired the immune response to poliovirus vaccines. The adverse effects of coinfection were considered clinically insignificant. PMID- 1415072 TI - Cephalexin and penicillin in the treatment of group A beta-hemolytic streptococcal throat infections. AB - OBJECTIVE: To determine whether cephalexin or penicillin is more effective in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children. DESIGN: Randomized, double-blind, crossover study conducted from 1981 to 1984. SETTING: Seven pediatric practices in the United States, including private offices and pediatric clinics. PARTICIPANTS: Of the 654 patients, 525 children and adolescents with clinical evidence of tonsillitis or pharyngitis and throat cultures positive for group A beta-hemolytic streptococcal infection were evaluable. Eighty percent of patients completed the study; none were withdrawn because of adverse reaction. SELECTION CRITERIA: Children and adolescents who had acute illness suggestive of group A beta-hemolytic streptococcal infection were enrolled in the study. Treatment was continued if the throat culture was positive for group A beta-hemolytic streptococcal infection. INTERVENTIONS: Four doses of cephalexin and penicillin (27 mg/kg per day) were prescribed to be taken on an empty stomach for 10 days. MEASUREMENTS/MAIN RESULTS: Symptomatic clinical failure occurred in 8% of penicillin-treated patients and in 3% of cephalexin treated patients. Bacteriologic failure rates were 11% in the penicillin treatment group and 7% in the cephalexin treatment group. The combined treatment failure rate of clinical relapse plus asymptomatic bacteriologic failure was 19% in the penicillin treatment group and 10% in the cephalexin treatment group. Paired antistreptolysin-O titer increased significantly in 62.3% of penicillin treated patients and in 64.2% of cephalexin-treated patients. Similarly, anti DNase B titers rose 52.2% in penicillin-treated patients and 52.4% in cephalexin treated patients. CONCLUSION: Cephalexin is a more effective drug than penicillin in the treatment of group A beta-hemolytic streptococcal throat infection in children. PMID- 1415073 TI - Transient aplastic crisis in patients with sickle cell disease. B19 parvovirus studies during a 7-year period. AB - OBJECTIVE: To determine (1) the proportion of cases of transient aplastic crisis (TAC) in patients with sickle cell disease due to B19 parvovirus infection in several years, (2) longitudinally, the immune response to B19 parvovirus infection, and (3) whether patients with sickle cell disease experience recurrent or chronic B19 parvovirus infection. DESIGN: Prospective evaluation of patients with sickle cell disease and TAC to find evidence of B19 parvovirus infection and, if present, to document the pattern of serologic response with time. SETTING: Large urban teaching hospital. PATIENTS: Patients younger than 18 years with sickle cell disease who were admitted to the hospital with a diagnosis of TAC or who developed TAC while in the hospital for other reasons. Follow-up serologic studies of B19 parvovirus infection were done in eight patients. MEASUREMENTS/MAIN RESULTS: Serum was tested for B19 parvovirus DNA/viral particles and specific anti-B19 parvovirus IgM and IgG antibodies. B19 parvovirus DNA/viral particles were detected in 11 (21%) of 53 patients with TAC. Specific anti-B19 parvovirus IgM antibodies were detected in 34 (64%) of the 53 patients. Overall, 36 (68%) of 53 patients with TAC had evidence of acute B19 parvovirus infection as shown by the detection of B19 DNA parvovirus and/or specific anti B19 parvovirus IgM antibodies in acute-phase serum. Follow-up serologic studies in eight patients with acute infection revealed disappearance of B19 parvovirus DNA/viral particles and anti-B19 parvovirus IgM antibodies and persistence of anti-B19 parvovirus IgG antibodies for up to 3 1/2 years after the diagnosis of acute B19 parvovirus infection. No patient had evidence of recurrent or chronic B19 parvovirus infection. CONCLUSIONS: Approximately 70% of cases of TAC in patients with sickle cell disease identified in a 7-year period were caused by acute B19 parvovirus infection. Once detected, anti-B19 parvovirus IgG antibodies remain detectable for several years. There was no evidence of chronic or recurrent B19 parvovirus infection in patients with sickle cell disease. PMID- 1415074 TI - Adenovirus infection and childhood intussusception. AB - OBJECTIVE: To investigate the possible relationship between enteric adenovirus types 40 and 41 and intestinal intussusception in children. DESIGN: Prospective, case-control patient study. PATIENTS: Sixty-three consecutive children suspected clinically of having intestinal intussusception were enrolled in this study. Of these, 25 children (mean age, 1.4 years; range, 3 months to 5 years) had barium enema examination-proved intussusception. Age-matched normal controls (24) and controls with diarrhea (21) were obtained within 1 month of the index case. MEASUREMENTS AND RESULTS: Stools were tested for the presence of nonenteric adenovirus and enteric adenovirus using a monoclonal antibody-based enzyme immunoassay. Five (20%) of 25 children with intussusception had nonenteric adenovirus in their stools compared with one (4%) of 24 normal controls, none (0%) of 21 of the controls with diarrhea, and none (0%) of 37 patients suspected of having intussusception who had negative results on barium enema examination. However, no stool samples were positive for enteric adenovirus. CONCLUSIONS: Nonenteric adenovirus infection and intestinal intussusception may be associated. However, because enteric adenovirus was not found in any of the groups studied, no conclusions can be made regarding their possible influence on the risk for developing intussusception. PMID- 1415075 TI - Are we educating a medical professional who cares? AB - We examined four domains in which physicians must demonstrate their capacity for caring. These include the knowledge base that forms the foundation for the practice of medicine, the personal characteristics and attributes that a physician brings to the profession, the individual patients for whom the physician accepts responsibility, and the society in which the physician lives. We conclude that the system of medical education does produce caring physicians. The profession's history of self-evaluation and criticism should not obscure medicine's real success in meeting its responsibility to care as well as to cure. PMID- 1415076 TI - Magnetic resonance imaging of the pituitary area in children treated for acute lymphoblastic leukemia with low-dose (18-Gy) cranial irradiation. Relationships to growth and growth hormone secretion. AB - OBJECTIVE: To determine the effects of 18-Gy cranial irradiation on growth, growth hormone (GH) secretion, and pituitary magnetic resonance imaging in children who underwent previous irradiation for treatment of acute lymphoblastic leukemia. DESIGN: Clinical survey. SETTING: Department of Pediatrics of the University of Bologna (Italy). PATIENTS: Ten boys and 18 girls who were treated for acute lymphoblastic leukemia; median age at diagnosis was 3.1 years and at the end of follow-up was 11.5 years. MEASUREMENTS AND RESULTS: Height was periodically measured from diagnosis until the end of follow-up, when GH secretion study and magnetic resonance imaging were performed. The mean height SD score was significantly lower than at diagnosis only at the end of treatment. Nocturnal mean GH concentration and GH response to pharmacological tests (arginine and levodopa [L-dopa]) were pathological in 22 cases (81.5%) and 18 cases (64.3%), respectively. Sixteen cases (59.2%) had a blunted GH release to the three tests. Mean pituitary anterior lobe height was reduced and seven subjects (25%) showed an empty sella. CONCLUSIONS: Cranial irradiation with 18 Gy does not seem to influence the growth pattern of most children who are treated for acute lymphoblastic leukemia, despite severe impairment of GH secretion and morphological abnormalities of the sellar area. However, a follow-up until final height is necessary. PMID- 1415077 TI - Effect of educational program on compliance with glove use in a pediatric emergency department. AB - OBJECTIVE: To investigate the effect of an educational program on compliance with glove use in a pediatric emergency department. DESIGN: Without their knowledge, participants were observed for routine use of gloves during vascular access procedures before and after an educational program. Participants with up to 3 years' vascular access experience were defined as less experienced and those with 4 or more years' experience were defined as more experienced. Their success rates performing vascular access procedures with and without wearing gloves were also monitored. SETTING: Inner-city pediatric hospital emergency department. PARTICIPANTS: Twenty-three emergency department registered nurses. INTERVENTIONS: A 30-minute lecture with slides, written materials, and posters addressing the reasons and need for universal precautions, and recommended methods of barrier precautions to prevent skin and mucous membrane exposure when handling sharp instruments. MEASUREMENTS/MAIN RESULTS: For the less experienced registered nurses, the compliance rate before the educational program was 70% and remained at about 93% afterward. For the more experienced registered nurses, the compliance rate before the program was only 15%. After the program, this compliance rate rose to 93%, but declined to only 50% by the fifth month. The registered nurses' success rate on the first attempt at vascular access while wearing gloves was 75% compared with 70% without gloves. CONCLUSION: Educational programs can result in a clinically significant increase in glove use by pediatric emergency department registered nurses. Long-term improvement was less pronounced for the group of more experienced registered nurses. We also observed that glove use does not appear to interfere with the proficient performance of vascular access procedures. PMID- 1415078 TI - Adolescent pregnancy. Gestational weight gain and maternal and infant outcomes. AB - OBJECTIVE: To clarify the advantages and disadvantages of large gestational weight gain among pregnant adolescents. DESIGN: Prospective, longitudinal survey. SETTING: Adolescent-oriented maternity program in Rochester, NY. PARTICIPANTS: One hundred forty-one poor, black, pregnant 12- through 19-year-olds grouped according to rate of gestational weight gain. Slow weight gain was defined as weight gain of less than 0.23 kg per week; average, 0.23 to 0.4 kg per week; and rapid, more than 0.4 kg per week. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Infants of rapid weight-gainers were significantly larger than infants of slower weight-gainers but did not experience fewer perinatal complications than other infants. Infants of slow weight-gainers were significantly smaller than infants of average and rapid weight-gainers and experienced more perinatal complications than other infants. Adolescents who gained weight rapidly retained more weight and, therefore, were more often obese after pregnancy. CONCLUSIONS: The advantages of large weight gains for pregnant adolescents and their infants are well-documented; this study demonstrates the importance of balancing the long term potential morbidity of maternal obesity against the benefits of enhanced fetal growth in formulating weight-gain recommendations for pregnant adolescents. PMID- 1415079 TI - Sexual assault examinations in children. The role of a statewide network of health care providers. AB - OBJECTIVE: To describe the formation of a statewide network of health care providers to care for child victims of sexual assault and to describe the patients seen by network providers. DESIGN: Clinical description, patient series. SETTING: Private practices, hospital clinics, and emergency departments. PARTICIPANTS: One thousand five hundred fifty-five child victims of suspected sexual assault. SELECTION: Children were referred to the Sexual Assault Findings Examination Network by the state's child protection agency, law enforcement agency, or the child's parent or guardian. No sampling system was used; the children compose the entire population of network patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Detailed physical examinations were performed on all patients, along with extensive collection of pertinent behavioral and historical information. Substantiation of child abuse-neglect by the state's child protection agency was higher in incidents in which SAFE Network providers evaluated the child as compared with all other providers, even where there was no physical evidence. CONCLUSIONS: The network concept, including mandatory training, standard data form and protocol utilization, uniform reimbursement, and continuing education, provides a more reliable level of care for child victims of sexual assault than is available with a variety of providers working independently. PMID- 1415080 TI - How will children and pregnant women fare under current national health insurance proposals? AB - OBJECTIVE: To compare the following five major national health insurance proposals and their implications for children and pregnant women: the MAtsui "play or pay" bill (HR 3393); the Russo Canadian-type bill (HR 1300); the Rockefeller "play or pay" bill (S 1177); the Stark Medicare-type bill (HR 650); and the president's market reform proposal. RESEARCH DESIGN: Using an analytic framework developed by the Association of Maternal and Child Health Programs, we examine the differences among the five proposals in basic approach, eligibility and enrollment, benefits, cost-sharing requirements, provider reimbursement, and cost-control measures. RESULTS: All of the plans, except for President Bush's, would provide coverage for virtually all children and pregnant women, using a combination of private and public approaches. President Bush's market approach provides financial incentives to purchase health insurance benefit plans that states can design within actuarial limits. The remaining four plans strive for uniformity in benefits, covering physician and hospital services in a manner similar to most plans today. Preventive care benefits extend beyond what has been offered in the past. The four plans differ sharply in their coverage of extended care services, with the Matsui and Russo bills covering the most generous package of benefits. The Rockefeller and Stark plans, on the other hand, require less cost-sharing for their basically preventive and primary care plans. CONCLUSIONS: Most of the health insurance proposals are aimed at extending preventive and primary care health insurance plans to more uninsured Americans. Only the Matsui bill devotes significant attention to developing a comprehensive benefit plan for children and pregnant women. Additional attention should be directed at extended care services for those with special health care needs, the future role of Medicaid, and the public health system infrastructure. PMID- 1415081 TI - Parental behavior in relation to physical activity and fitness in 9-year-old children. AB - OBJECTIVE: To examine the relationship between parental behaviors and physical activity and fitness in elementary school-aged children. DESIGN: Cross-sectional survey of students and parents. SETTING: Seven public elementary schools in a suburban southern California city. PARTICIPANTS: One hundred forty-eight fourth grade girls and 149 fourth-grade boys and their parents. Eighty-four percent were white. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Children's physical activity was indicated by self-report, data obtained from a monitor (accelerometer), and results of the mile run/walk. Multiple regression analysis, controlling for ethnicity and body mass index, was conducted separately for girls and boys to explain variation in child activity and fitness. Parents' reported physical activity was not associated with child activity or fitness. However, availability of transportation by parents to sport and fitness activities was significant (or nearly so) in two regressions for boys and in one regression for girls. Parents who played with their children had more active boys, based on self report, but verbal encouragement to be active was not significant in any model. CONCLUSION: The parental role as gatekeeper of access to activity and sport facilities deserves further study. PMID- 1415082 TI - Crack cocaine use and sexual behavior among psychiatric inpatients. AB - Rises in both crack cocaine use and incidence of sexually transmitted diseases have been recently reported. In this study, we investigated the relationship between crack cocaine abuse and sexual behavior in 50 psychiatric inpatients. The relationship between crack use and sexual behavior is a very complicated one, influenced by many variables such as the dose of crack used, the user's preexisting sexuality, gender, and psychiatric illness. Results indicated that while most of the subjects developed sexual disinterest and dysfunction with prolonged crack cocaine use, some of them became more sexually promiscuous and consequently contracted more sexually transmitted diseases. The implications of these findings regarding transmission of HIV among crack cocaine users are discussed. PMID- 1415083 TI - Perinatal substance abuse. AB - This article reviews medical, obstetrical, and neonatal complications of perinatal substance abuse. The psychological and social issues commonly encountered in drug-abusing pregnant women are also discussed. Treatment considerations that take into account the complex biopsychosocial parameters are presented. PMID- 1415084 TI - Age at first injection and HIV risk among intravenous drug users. AB - The relationship of age at first injection and HIV risk was explored in a nonblinded HIV seroprevalence study of intravenous drug users (IVDUs) admitted to methadone treatment in seven United States cities between February 1987 and June 1989. Comparisons were made of IVDUs who began injecting as adolescents, young adults, and adults in terms of drug use and sexual HIV risk behaviors and HIV serostatus. Early injectors consistently reported higher levels of drug-using risk behaviors (e.g., frequency of injection, frequency of needle sharing, and use of shooting galleries), and were more likely to be HIV seropositive. Among females, early injectors were also more likely to report sexual risk behaviors (e.g., multiple sex partners, prostitution). The relationship of age at first injection with selected risk behaviors and HIV serostatus was independent of subjects' age at interview, gender, and race/ethnicity. This study suggests that adolescent injectors are an important target group for HIV prevention efforts. PMID- 1415085 TI - Suicidal behavior and history of substance abuse. AB - Substance abuse is frequently associated with suicidal behavior. However, it is unclear to what degree substance abuse in a family member is related to suicide. In the present study, personal and family histories of substance abuse were examined in 716 psychiatric emergency room patients. Suicide attempters, suicide ideators, and nonsuicidal controls were compared across demographic, clinical, and substance abuse variables. Results showed that suicidal patients differed from nonsuicidal controls on many of the dependent variables. Suicidal patients were more likely to be depressed and report a history of previous suicidal tendencies. Also, alcohol and drug abuse occurred more frequently in suicidal patients. Furthermore, a family history of alcohol abuse was reported more often by suicidal than nonsuicidal patients. These patterns of substance abuse in suicidal patients were especially prominent among older subjects. Results are discussed in terms of the implications for identifying psychiatric emergency room patients at risk for suicide. PMID- 1415086 TI - Drug abuse history and treatment needs of jail inmates. AB - The current study evaluates the extent of prior drug use and psychosocial dysfunction related to drug use among 499 jail inmates referred to the Hillsborough County Sheriff's Office Substance Abuse Treatment Program. Results indicate that inmates were involved with drugs for an average of more than 7 years, and with cocaine for almost 5 years. The majority of inmates reported extremely heavy use of drugs in the month prior to the last arrest, including 83% that had used cocaine. Many drug-dependent inmates reported a shift over time from intranasal to freebase cocaine use. Half of all referrals indicated a pattern of regular use within a year of involvement with drugs. The need for lengthy, heavily structured, and intensive treatment approaches for drug dependent jail inmates is underscored by a history of chronic cocaine and polydrug abuse, a compulsive pattern of drug use, few successful periods of voluntary abstinence, and severe disruption in vocational, social, and psychological functioning. Their history of infrequent and unsuccessful involvement in rehabilitation programs reflects a significant need for compulsory treatment following release from jail, community supervision to ensure compliance with treatment, and development of linkages between jail drug treatment programs, courts, and community treatment providers. PMID- 1415087 TI - Parental leave. PMID- 1415088 TI - Helicobacter pylori and recurrence of duodenal ulcers. PMID- 1415089 TI - Parental leave for trainees in gastroenterology. The Ad Hoc Committee for Women in Gastroenterology, The American College of Gastroenterology. PMID- 1415090 TI - The effect of acupuncture on gastrointestinal function and disorders. AB - Acupuncture has been used empirically in clinical practice in China for several millenia and has recently drawn interest as a mode of anesthesia. Despite extensive investigation, the exact mechanisms of its analgesic action are unknown, but are thought to involve endogenous opioid peptides. Only recently have studies attempted to evaluate the effect of acupuncture on gastrointestinal function and disease. A review of studies from both the Chinese and Western literature supports the efficacy of acupuncture in the regulation of gastrointestinal motor activity and secretion through opioid and other neural pathways. However, no firm conclusion can be drawn about the effectiveness of acupuncture in the treatment of specific gastrointestinal disorders because of the lack of properly randomized controlled trials. PMID- 1415091 TI - Heatstroke: its clinical and pathological presentation, with particular attention to the liver. AB - Heatstroke is a potentially fatal disorder caused by an extreme elevation of body temperature. It is the most severe of the illnesses produced as a result of a high ambient temperature; however, it also may occur sporadically among individuals working or exercising in more favorable weather conditions, particularly early in their training before acclimatization occurs. The liver is a common site of tissue injury in cases of heatstroke and can be the site of fatal tissue injury in cases that survive the initial neurologic injury. Prompt early recognition of heatstroke as the entity responsible for a given patient's problems and effective early cooling with attention to expected complications can result in complete recovery in most cases. In a minority (< 10%) in whom neurologic injury has not resulted in an early death occurring within the first 2 3 days, the hepatic injury due to heatstroke can result in death that occurs a week or more after the onset of the heat stress, unless the liver is replaced. Recently, two such cases have been referred to the University of Pittsburgh for transplantation. On the basis of these two referrals and a review of the literature, we believe that this problem occurs more often than is currently appreciated, principally because of a lack of knowledge about the problem. In an attempt to correct this information deficit, this review was prepared. PMID- 1415092 TI - Smoking does not contribute to duodenal ulcer relapse after Helicobacter pylori eradication. AB - Cigarette smoking is believed to be one of the major factors influencing duodenal ulcer (DU) recurrence. However, the influence of cigarette smoking on DU recurrence after the eradication of Helicobacter pylori has not been separately addressed. The aim of this study was to investigate DU relapse rate in smokers and nonsmokers, both with confirmed eradication of H. pylori. Patients with H. pylori eradication, demonstrated at endoscopy 4 wk post-treatment, were included in the study. Smoking history was obtained with a standard questionnaire, and patients were followed endoscopically, both yearly and at symptomatic recurrence, to detect anatomical DU recurrence. Of the 197 (121M:76F) patients enrolled in the study and followed for 1-6 yr, 80 (41%) were smokers, smoking 5-40 cigarettes/day. The 117 (59%) nonsmokers included 31 (26%) patients who had ceased smoking 4-20 yr ago. Another seven (9%) smokers ceased smoking during the follow-up period. In the 197 patients with eradicated H. pylori and cured DU, there has been no recurrence of ulcer, regardless of smoking status. We conclude that in patients with DU in whom H. pylori infection is eradicated, ulcer disease does not recur, as observed for up to 6 yr. Furthermore, cigarette smoking is not a risk factor for DU recurrence, provided H. pylori is eradicated. PMID- 1415093 TI - Serum gastrin is not higher in subjects with colonic neoplasia. AB - Two previous studies have shown higher circulating gastrin levels in subjects with colonic neoplasia than in colonoscopy-negative controls. In this much larger study, sera were collected from fasting subjects undergoing colonoscopy. Colonoscopy with biopsy classified participants as having colonic adenomas (N = 139), colon carcinoma (N = 29), or controls without colonic neoplasia (N = 150). Frozen, stored sera were later analyzed for gastrin by radioimmunoassay. Serum gastrin values were no higher in subjects with colonic adenomas or carcinoma than in colonoscopy-negative controls. We conclude that elevated serum gastrin levels play little, if any, role in the initiation of colonic neoplasia. PMID- 1415094 TI - Nonsteroidal antiinflammatory drug-associated gastric ulcers do not require Helicobacter pylori for their development. AB - Nonsteroidal antiinflammatory drugs (NSAIDs) have been linked with a high incidence of ulcer complications. Histologic gastritis is present in most patients with standard peptic ulcers, and this gastritis is generally related to Helicobacter pylori (HP). We questioned whether gastric ulcers associated with nonsteroidal antiinflammatory drugs (NSAIDs) develop via a novel mechanism, distinct from the usual HP-gastritis-ulcer diathesis. Two groups of patients with newly discovered gastric ulcers were assessed: 1) daily NSAID use > 1 month (n = 19), 2) no NSAID use (n = 36). Biopsy specimens from the rim of the ulcer and adjacent normal mucosa were coded, randomized, and evaluated for histologic features and HP. HP prevalence was significantly lower in the NSAID group (10/19 (53%) vs. 30/36 (83%), p = 0.01). In biopsies from the ulcer rim, inflammatory cell density and epithelial abnormalities were significantly less in the NSAID group than in the no-NSAID group. Biopsies from adjacent mucosa exhibited the same trends, but the differences did not reach statistical significance (inflammation, p = 0.06; epithelium, p = 0.05). HP-positive patients had similar inflammation and epithelium scores, whether or not they took NSAIDs. However, HP negative NSAID patients had significantly lower scores than HP-positive NSAID users (inflammation, 0.6 +/- 0.2 vs. 2.4 +/- 0.4; epithelium, 1.1 +/- 0.6 vs. 3.5 +/- 0.7). Patients with NSAID-associated gastric ulcers have a lower prevalence of HP and less histologic gastritis than patients with non-NSAID gastric ulcers. The gastritis is related to the underlying HP and not to NSAID ingestion. NSAID associated gastric ulcers may represent a major subset of peptic ulcers that do not require HP for their development. PMID- 1415095 TI - Helicobacter pylori-negative gastric ulcer. AB - Causes of Helicobacter pylori (HP)-negative gastric ulcers (GUs) have not previously been systematically studied. In this study we examined possible causes of HP-negative GUs. Among 115 consecutive patients with endoscopic diagnoses of GU, 71 (62%) had HP infection, and 44 (38%) were found to be HP-negative. Of the 71 HP-positive patients, 47 (66%) had no other detectable causal factors, 21 (30%) were regularly taking nonsteroidal antiinflammatory drugs (NSAIDs), and three (4%) had malignant GU. Of the 44 HP-negative patients, 29 (66%) were taking NSAIDs, two (5%) had a malignant GU, whereas 13/44 (30%) (11% of total 115) patients had no identifiable cause. These patients were classified as having "idiopathic GU." Some 38/115 (33%) GUs occurred on the lesser curve, and these were more often (p = 0.012) HP-positive (76%) than prepyloric GUs (60/115 (52%)). We conclude that although most patients have an identifiable cause of GU, around 11% will have no apparent contributing factor. HP-positive GUs are more frequently located on the lesser curve. It is now important to identify the cause of GU, because this may dictate choice of management. PMID- 1415096 TI - Is rectal biopsy necessary in irritable bowel syndrome? AB - Many physicians obtain a rectal biopsy from patients with irritable bowel syndrome (IBS) in order to exclude melanosis coli and collagenous or microscopic colitis. To determine the value of routine rectal biopsy in IBS, 89 patients and 59 controls were administered a bowel questionnaire, and a rectal biopsy was obtained at sigmoidoscopy. IBS patients were 82% female and averaged 44 yr. Eighty-nine percent fulfilled three or more Manning criteria, and 84% fulfilled the Rome criteria for IBS. The 59 control subjects were 37% female, and averaged 57 yr. Only 15% fulfilled three or more Manning criteria, and 5% the Rome criteria. The 148 rectal biopsies were examined histologically by a pathologist whose methods were validated by a second pathologist. Although minor changes previously reported with phosphate enemas were observed, not a single subject had melanosis coli or fulfilled criteria for microscopic or collagenous colitis. Thus, patients with an endoscopically normal colon and a diagnosis of IBS made by established criteria are unlikely to have histologic abnormalities in the rectum. Rectal biopsies are costly and unnecessary in the investigation of IBS. PMID- 1415097 TI - Preoperative testing for fecal occult blood: a questionable practice. AB - The benefit of fecal occult blood testing (FOBT) in patients without gastrointestinal symptoms who are hospitalized for an elective surgical procedure is uncertain. To resolve this issue, we analyzed the costs and benefits of preoperative FOBT by the model of a decision tree. In 2- and 3-way sensitivity analyses, the costs of diagnostic and therapeutic procedures and the probabilities of their various outcomes are varied simultaneously so that we might study their joint influence on the outcome of the decision analysis. The decision analysis shows that preoperative FOBT is associated with a smaller benefit than would be its omission. The higher cost and lower net benefit of preoperative FOBT reflect the impact of false-positive tests for occult blood. False-positive FOBT leads to expenditures for negative gastrointestinal work-ups, increased procedural costs, and a diminished rate of success for the elective surgical procedure, by delaying it. This outcome of the analysis is insensitive to large variations in the costs and probabilities built into the model. We conclude that screening for fecal occult blood provides no benefit if done routinely in patients who are hospitalized for any major surgical procedure. PMID- 1415098 TI - Metastatic tumors to the upper gastrointestinal tract: endoscopic experience. AB - Metastatic tumors to the upper gastrointestinal tract were identified by esophagogastroduodenoscopy in 14 patients. Malignant melanoma, breast cancer, and lung cancer were the most common primary cancers in four, three, and three patients, respectively. Osteogenic sarcoma, renal cell carcinoma, Meckel cell carcinoma of the skin, and germ-cell tumor were the primary cancer in the remaining four. The esophagus was involved in three patients, the stomach in 13, duodenum in four, and papilla of Vater in one. Upper gastrointestinal bleeding and anemia were the most common presenting features. There was correlation between symptoms and endoscopic findings in all patients. Involvement of gastrointestinal tract at endoscopy was the initial and only evidence of metastases in all patients without evidence of metastases elsewhere, as evidenced by other diagnostic tests in any of these patients. Endoscopic biopsies and/or brush cytology provided histologic diagnosis in all 14 patients. The endoscopic and nonendoscopic literature regarding metastases to the upper gastrointestinal tract is reviewed. PMID- 1415099 TI - Increased gallbladder residual volume in nonresponders to extracorporeal shock wave lithotripsy of gallbladder stones. AB - In a prospective study of 63 patients, we purposed to determine whether gallbladder contractility or gallbladder volume before biliary lithotripsy are predictors of fragment disappearance. Percentage gallbladder contraction was calculated from the fractional difference in the sonographically measured gallbladder volume after a standard fatty meal. Statistical analysis showed no significant differences in gallbladder contractility between the fragment-free group and the residual-fragment group before (77.2 +/- 12.7% vs. 71.9 +/- 19.3%; p = 0.1044) biliary lithotripsy and after the termination of adjuvant cholelitholysis therapy (76.4 +/- 12.9% vs. 72.2 +/- 17.1%; p = 0.1341). Before treatment, there was no significant difference in fasting gallbladder volume in either group (29.9 +/- 15.4 ml vs. 36.6 +/- 18.8; p = 0.0682), but postprandial gallbladder volume was greater in nonresponders (10.4 +/- 9.4 ml vs. 6.5 +/- 3.8; p = 0.0164). After termination of the therapy, both the fasting gallbladder volume (41.2 +/- 24.2 ml vs. 29.8 +/- 10.3 ml; p = 0.0093) and the postprandial gallbladder volume (11.9 +/- 11.7 ml vs. 7.3 +/- 5.3 ml; p = 0.0267) were greater in the residual-fragment group. The increase of the fasting gallbladder volume in the residual-fragment group was statistically not significant. Our results indicate that the increased residual volume is a significant cause of therapeutic failure in nonresponders. PMID- 1415100 TI - Portal and systemic hemodynamics and humoral factors in cirrhosis with and without ascites. AB - The pathogenesis of salt and water retention in cirrhosis remains unclear. Systemic and portal hemodynamic parameters, including cardiac output, portal pressure gradient and systemic vascular resistance, were measured in six patients with untreated ascites and in six patients with hepatic cirrhosis with no history of ascites. Renal blood flow, urinary volume, and humoral factors, including plasma renin, aldosterone, angiotensin II, and urine kallikrein, were measured. Significant differences were seen between the two groups in urine volume, urine sodium and fractional sodium excretion, plasma angiotensin II, and the ratio between plasma renin activity and urinary kallikrein excretion (PRA:UKallV). A strong correlation existed between urinary sodium excretion and the PRA:UKallV ratio. No significant differences were detected between the groups in portal, renal, and systemic hemodynamics. The present results suggest that humoral changes occur early in ascites. Altered relationships between intrarenal hormone systems, such as the renin-angiotensin and kallikrein-kinin systems, may be important in salt and water retention. PMID- 1415101 TI - A prospective, randomized, blinded trial of cytological yield with disposable cytology brushes in upper gastrointestinal tract lesions. AB - Brush cytology is an important technique in the diagnosis of upper gastrointestinal tract lesions. Optimum cytological yields depend on cellularity (a measure of the amount of epithelial cellular material) and preservation (a measure of artifact induced by desiccation). We sought to determine the cytological yield of four disposable cytology brushes. Seventy-eight patients were studied, with a total of 80 disposable cytology brushes from four different manufacturers (Wilson-Cook, Microvasive, Mill-Rose, and Hobbs). Cellularity and preservation were assessed in a blinded fashion by experienced cytotechnologists. There was no significant difference in cellularity between the different non disposable brushes. However, the Wilson Cook disposable cytology brush was significantly superior to the other disposable cytology brushes (P < 0.05) with regard to preservation. Its unique design features (longer head and more acutely angled bristles) may account for the better results. PMID- 1415102 TI - Prospective evaluation of a peritoneal dialysis catheter system for large volume paracentesis. AB - Large volume paracentesis is becoming a popular form of therapy for patients with massive ascites and cirrhosis. Although the physiologic effects of the removal of large amounts of ascitic fluid have been well described, the techniques utilized to perform the procedure are either not well documented or not currently available. Over a 13-month period, 52 patients with moderate to severe ascites have undergone 73 large volume paracenteses with a peritoneal dialysis catheter system. The mean volume of ascitic fluid removed was 7.6 L, with a mean time of removal of 129 min. Total paracentesis was accomplished within 1 h in 38% of procedures. The most common site for paracentesis was the left lower quadrant. Complications related to the procedure were few, the most common being a self limited ascitic fluid leak at the sight of paracentesis. No patient experienced intestinal perforation, peritonitis, or a significant change in serum creatinine after the procedure. The widely available peritoneal dialysis catheter system represents a safe and rapid technique for the removal of large quantities of ascitic fluid. PMID- 1415103 TI - A technique for segmental rectal and colonic perfusion in humans. AB - To enable a better characterization of pathophysiologic processes in colon and rectum, we have developed a perfusion technique for collection of soluble substances and cells from standardized intestinal segments. A tube with balloons attached to its outer wall was endoscopically introduced into the rectum and sigmoid colon, and its position ascertained fluoroscopically. The balloons delimited two segments, one in the sigmoid colon and one in the rectum. The segments were simultaneously perfused by a buffer at 37 degrees C. After a 30-min rinsing period, perfusate and cells were collected at 20-min intervals. Of 51 attempted perfusions, 45 were successfully completed. Recovered volumes equaled those infused. Leakage from the proximal intestine to the segments was negligible. In 18 healthy volunteers, the mean perfusate concentration from the rectal segment was 57.5 (27.5-120.2) mg/L for albumin, 1.3 (1.0-1.7) micrograms/L for eosinophil cationic protein, 5.1 (2.8-9.5) ng/L for prostaglandin E2, and 61.7 (41.7-89.1) micrograms/L for hyaluronan, and all values were lower in the sigmoid segment. Steady state conditions were achieved from the second perfusion period. The perfusate contained 4-80 x 10(4) cells, more than 95% of which were epithelial cells. The technique is safe, has a good subject compliance, and seems to be a valuable tool in investigations on quantitative release of soluble substances and cells in, e.g., colorectal inflammation. PMID- 1415104 TI - Tyrosylprotein sulfotransferase activity is increased in human gastric mucosa of alcoholics. AB - Sulfation plays a major role in the processing of secretory proteins. We report here on tyrosylprotein sulfotransferase activity in human gastric mucosa of normal and alcoholics. The tyrosylprotein sulfotransferase was identified in the Golgi-enriched fraction. In alcoholics, the activity of sulfotransferase was 2- to 3-fold higher than in normals. However, no change in the activity of UDP glucose-ceramide glucosyltransferase, a marker for Golgi, between alcoholics and normals was observed. The tyrosylprotein sulfotransferase enzyme required Triton X-100, MnCl2 and 5'-AMP, and obtained optimum activity at pH 6.8 in the presence of 0.5% Triton X-100, 20 mM MnCl2, 50 mM NaF, and 2 mM 5'-AMP. The apparent Km for poly-Glu6, Ala3, Tyr1 (EAY; 47,000) was 1.9 x 10(-6) M and for 3' phosphoadenosine 5'-phosphosulfate (PAPS), 1.4 x 10(-6) M. The results suggest that alcohol abuse causes enhancement in the expression of gastric mucosal tyrosylprotein sulfotransferase activity. PMID- 1415105 TI - Upper gastrointestinal bleeding from Merkel cell carcinoma. AB - Merkel cell carcinoma is a rare small cell carcinoma of the dermis with aggressive clinical features and frequent local recurrence. Intra-abdominal spread of the cancer has previously been noted primarily in the liver and retroperitoneal nodes. We report a patient with previously diagnosed Merkel cell carcinoma of the right buttock with metastases to the stomach and duodenum presenting with acute upper gastrointestinal bleeding. PMID- 1415106 TI - Bleeding from a Meckel's diverticulum after the use of ibuprofen. AB - A Meckel's diverticulum is an unusual site of gastrointestinal bleeding in adults. Bleeding often results from ulceration of ileal mucosa that lies adjacent to ectopic gastric mucosa. We report on a 27-yr-old man who bled from a Meckel's diverticulum after receiving oral ibuprofen, a nonsteroidal antiinflammatory drug. Examination of the resected diverticulum revealed fundal-type gastric mucosa with inflammation, submucosal hemorrhages, erosions and ulceration in the absence of Helicobacter pylori. The ileal mucosa was spared in this patient. These features suggest that oral ibuprofen caused damage to the ectopic gastric mucosa, precipitating significant hemorrhage. This is the first report in the English literature of such an occurrence. PMID- 1415107 TI - Severe hemorrhage caused by gastrointestinal Kaposi's syndrome in patients with the acquired immunodeficiency syndrome: treatment with endoscopic injection sclerotherapy. AB - Kaposi's sarcoma (KS) is the most common tumor among HIV-infected individuals, but its involvement in the gastrointestinal tract was reported long before the AIDS epidemic. Although most cases of gastrointestinal KS are asymptomatic, advanced lesions may occasionally result in a severe and life-threatening hemorrhage that requires immediate treatment. At the NYU Medical Center, we have seen three AIDS patients present with severe upper tract bleeding (> 8 U/48 h) from KS lesions of the antrum, fundus, and duodenum. The last patient was also bleeding from an ulcerated rectal KS lesion. Because all three patients had a coexisting thrombocytopenia (platelets < 50,000/mm3) and were poor operative risks, injection sclerotherapy was performed. All four KS lesions stopped bleeding, and three out of the four lesions decreased in size. To our knowledge, this is the first report of successfully using sclerotherapy to treat severe hemorrhage due to gastrointestinal KS. PMID- 1415108 TI - Intestinal herpes simplex infection presenting with intestinal perforation. AB - A 77-yr-old man who had received systemic steroids for more than 6 yr presented with an acute abdomen. Laparotomy revealed an ulcerative jejunitis with purulent peritonitis. The patient underwent resection of involved bowel followed by a 10 day course of aciclovir, with excellent results. Pathologic examination showed a necrotizing enteritis with intranuclear inclusions typical of Herpesvirus that reacted immunocytochemically with antibodies to herpes simplex virus types I and II. A rising herpes simplex virus serum antibody titer confirmed the diagnosis. Intestinal herpes infection with perforation should be added to the list of complications from herpes simplex in the immunocompromised patient. PMID- 1415109 TI - Iron malabsorption in a patient with large cell lymphoma involving the duodenum. AB - Iron malabsorption compounded the anemia in a patient with diffuse large cell lymphoma involving the small intestine. Both upper gastrointestinal series with small bowel follow-through and computerized tomographic scan demonstrated lymphomatous involvement of the duodenum and proximal jejunum by a retroperitoneal mass. An oral iron-loading absorption test was consistent with malabsorption of iron. After two cycles of systemic chemotherapy, the retroperitoneal mass resolved and the iron loading test normalized. PMID- 1415110 TI - Arcuate ligament syndrome mimicking celiac occlusion. AB - In a patient with weight loss and a systolic epigastric murmur, aortography demonstrated positional celiac axis occlusion. Color Doppler imaging of the celiac axis showed occlusion in the supine position, but patency was documented during deep inspiration and with the patient in the upright position. This report documents a rare example of extreme celiac axis compression with position dependent celiac patency. PMID- 1415111 TI - Anal tuberculosis: report of two cases and literature review. AB - Tuberculous involvement of the anus is an extreme rarity. We report two cases of anal tuberculosis and discuss the clinical features, the difficulty in differentiating from Crohn's disease, and the diagnostic aspects in the context of the pertinent medical literature. PMID- 1415112 TI - Unexpected anomalies of the common bile and pancreatic ducts. PMID- 1415114 TI - Partial regression of childhood Barrett's esophagus after fundoplication. AB - A 12-yr-old boy presented with Barrett's esophagus, the nature and extent of which were thoroughly documented with multiple endoscopic biopsies. He had an excellent symptomatic response to antireflux surgery. Radiologic studies, esophageal manometry, and intraesophageal pH studies were performed before surgery and at intervals thereafter, and documented the success of antireflux surgery. Within 2 yr of surgery, there was endoscopic and histologic evidence of squamous regression of columnar mucosa, and this process of regression to squamous epithelium continued over a further 3 yr. This case suggests that partial squamous regression of Barrett's esophagus may occur in children. Studies dealing with regression are reviewed and proposals are made for a standardized approach to its documentation. PMID- 1415113 TI - Mesenteric fibromatosis presenting as fever of unknown origin. AB - We report a case of fibromatosis, soft tissue tumors that are benign histologically, but exhibit behavior intermediate between benign and malignant diseases. Mesenteric fibromatosis grows vigorously without a general inflammatory reaction, and its symptoms are the result of obstruction and/or compression of the intestine. However, in our case, the general inflammatory reactions of fever and C-reactive protein (CRP) elevation was present at an early stage. Because this inflammatory reaction disappeared after surgical resection, it may have been induced by some inflammatory factors produced in the tumor, such as those produced in inflammatory fibrous histiocytoma. We found that computed tomography was useful in the detection of the cause of fever of unknown origin, and suggest that it should be recommended in cases of long-lasting unexplainable fever. PMID- 1415115 TI - Is the chronic cougher a refluxer? PMID- 1415116 TI - Gender and pancreatitis: do the ducts make the difference? PMID- 1415117 TI - Laparoscopic cholecystectomy for gallbladder cancer!!? PMID- 1415118 TI - Ulcerative esophagitis during primary HIV infection. PMID- 1415119 TI - Esophageal perforation in association with Herpesvirus infection: report of an autopsy case. PMID- 1415120 TI - Source of Helicobacter pylori infection: studies in abattoir workers and pigs. PMID- 1415121 TI - Tamponade of biopsy-induced hemorrhage via submucosal hematoma formation. PMID- 1415122 TI - Antirheumatoid second-line drugs and mucosal injury by NSAIDs. PMID- 1415123 TI - Liver involvement in secondary syphilis. PMID- 1415124 TI - Dumping syndrome and the regulation of peptide YY with verapamil. PMID- 1415125 TI - Report of Eales' disease and ulcerative colitis in the same patient. PMID- 1415126 TI - Monitoring chemical exposure using breast milk: a methodological review. AB - Retrospective exposure assessments are often a major weakness in environmental epidemiologic studies. Many environmentally important chemicals are persistent lipophilic compounds which partition into fat and breast milk. The analysis of these chemicals in breast milk provides a noninvasive means of collecting large volumes of a biologic fluid that correlates well with body burden. This may provide an integrated measure of cumulative absorption over several years which can be used to assess exposure in several different epidemiologic study designs. However, consideration of toxicokinetic principles in the study design is important in order to allow for maternal and other factors unrelated to exposure which may influence breast milk concentrations. These factors include maternal age, parity, maternal body weight, time of sampling during the lactation period, and fat content of the breast milk. Failure to use standardized entrance criteria and to allow for the above factors in the analysis and interpretation of the study results may lead to invalid conclusions regarding past exposures. Allowance must also be made for the restrictions on the sampling frame available in any epidemiologic study using breast milk analysis. Published studies to date often have had several methodological deficiencies. With the introduction of biologic specimen banks, breast milk collection and analysis should play an important role in future epidemiologic studies, especially those investigating health outcomes in infants. PMID- 1415127 TI - Air-conditioning and mortality in hot weather. AB - A cohort of 72,740 persons for whom information on household air-conditioning was available was monitored for mortality via the National Death Index from April 1980 through December 1985. A total of 2,275 deaths occurred among the members of this cohort. The basic question addressed was whether persons in households with air-conditioning experienced lower death rates during hot weather than persons in households without air-conditioning. This question was examined for both central and room air-conditioning. The analysis was based on a state-by-state approach, that cross-tabulated deaths by air-conditioning status (yes or no) and average temperature during the month of death (less than 21.2 degrees C (less than 70 degrees F) or greater than or equal to 21.2 degrees C (greater than or equal to 70 degrees F)). The Mantel-Haenszel and sign tests were used to summarize the data. For central air-conditioning versus no air-conditioning, statistically significant benefits (p less than 0.05, Mantel-Haenszel test) were observed for the overall total, for females, for persons not in the labor force, and for persons living in fewer than six rooms. These groups had more exposure to air conditioning. The relative risk for the total group was 0.58, implying that in hot weather, the death rate for persons who had central air-conditioning was 42 percent lower than the rate for persons who did not have air-conditioning, after confounding variables had been controlled for. For room air-conditioning versus no air-conditioning, the odds ratio for the total group was 0.96, which was not significantly different from 1.0, suggesting that no real benefit was derived from room air-conditioning. Some reasons for the lack of a demonstrable benefit for room air-conditioning are given. PMID- 1415128 TI - The relation between serum insulin levels and 8-year changes in lipid, lipoprotein, and blood pressure levels. AB - Hyperinsulinemia is associated with an adverse pattern of cardiovascular risk factors, including obesity, elevated triglyceride levels, low levels of high density lipoprotein (HDL) cholesterol, and elevated blood pressure. Whether hyperinsulinemia precedes (and perhaps causes) this deterioration in the risk factors or merely accompanies the deterioration is controversial. We therefore examined the 8-year changes in lipids, lipoproteins, and blood pressure as a function of baseline levels of fasting insulin in 1,383 nondiabetic Mexican American and non-Hispanic white subjects enrolled between October 1979 and November 1982 in the San Antonio Heart Study, a population-based longitudinal study of cardiovascular risk factors and diabetes in San Antonio, Texas. After age and concomitant changes in body mass index were adjusted for, fasting insulin at baseline was found to be correlated positively with 8-year changes in triglyceride levels and negatively with 8-year changes in HDL cholesterol levels (p less than 0.05). Among the non-Hispanic whites, insulin was more strongly correlated with a decline in HDL cholesterol levels in women than in men (p less than 0.001). Fasting insulin was also positively correlated with changes in both systolic and diastolic blood pressure in non-Hispanic whites, but not in Mexican Americans, although these correlations were slightly diminished and no longer achieved statistical significance after subjects receiving antihypertensive medications were excluded. These results support the hypothesis that in nondiabetic subjects, insulin has a direct regulatory effect on triglyceride and HDL cholesterol levels. These data provide evidence for a possible role for insulin in blood pressure regulation, at least in non-Hispanic whites, although further analysis of this issue is warranted. PMID- 1415129 TI - Aging and total cholesterol levels: cohort, period, and survivorship effects. AB - This analysis describes the association of age with the serum total cholesterol level in 5,010 participants in a geriatric health screening program. Cholesterol levels were measured annually in participants monitored for up to 12 years. The association of age with cholesterol level is described via three approaches: cross-sectional analysis, descriptive longitudinal analysis, and longitudinal analysis using statistical modeling. The results were compared to examine the influence of cohort, period, and survivorship effects on the association between age and cholesterol. In cross-sectional analysis, the cholesterol level was fairly constant for the ages of 65 to 75 years, but decreased by 21% over the age range from 75 to 95 years. Descriptive longitudinal analysis suggested that both cohort and period effects were influencing the cross-sectional findings. In longitudinal analysis adjusting for both cohort and period effects, the findings were similar to those from cross-sectional analysis for the ages of 65 to 75 years, but from the ages of 75 to 95 years, cholesterol decreased by only 9%- half as great a decline as that estimated from cross-sectional analysis. When longitudinal data were limited to those with complete follow-up, the predicted decline for the age range from 75 to 95 years was only 6%. Although this flattening of the age trend was suggestive, there was no conclusive evidence that it reflected an association between baseline cholesterol and loss to follow-up. PMID- 1415130 TI - Fatal stroke and use of oral contraceptives: findings from a case-control study. AB - A case-control study of women less than 40 years of age in England and Wales was performed to evaluate the risk of fatal stroke associated with the use of the newer, low-dose oral contraceptives. Included were 296 cases with subarachnoid hemorrhage, 105 cases with other hemorrhagic stroke, and 21 cases with occlusive stroke, all of which occurred during 1986-1988. Two living controls per case, matched for age and marital status, were chosen from the general practice lists. The power of the study was such that the minimum significant increased relative risk of subarachnoid hemorrhage associated with ever having used oral contraceptives that could have been detected with 90% certainty was 1.6; the equivalent value for occlusive stroke was 28.4. Relative risk was estimated by conditional logistic regression allowing for matching. The adjusted relative risk of subarachnoid hemorrhage associated with oral contraceptives was estimated to be 1.1 (95% confidence interval (CI) 0.6-1.9) for current use and 1.3 (95% CI 0.9 1.8) for ever use, while the equivalent relative risk of an occlusive stroke associated with ever use was 4.4 (95% CI 0.8-24.4). Oral contraceptive use may be associated with a small increase in the risk of subarachnoid hemorrhage. These data are consistent with a substantial increase in the risk of occlusive stroke associated with oral contraceptive use. PMID- 1415131 TI - The risk of epithelial ovarian cancer in short-term users of oral contraceptives. AB - Short-term use (less than 1 year) or oral contraceptives has been associated with increased to slightly decreased risks of epithelial ovarian cancer in several studies. To determine what might account for a statistically significant 40% reduction in risk associated with as little as 3 to 6 months of use, a finding previously reported from the Cancer and Steroid Hormone Study, and to consider the implications for mechanisms of pathogenesis, the authors compared numerous characteristics of short-term users of oral contraceptives (41 cases, 412 controls) with those of never users (242 cases, 1,517 controls). The reduced risk among short-term users was consistently restricted to women who stopped using oral contraceptives for medical reasons, which were essentially side effects; there was little evidence of a protective effect among women who stopped for nonmedical reasons. Factors such as age, parity, family history of ovarian cancer, estrogen dose, history of sterilization, and latency (interval from first use) could not account for the finding. These analyses suggest that short-term use of oral contraceptives has little to no effect per se on reducing the risk of epithelial ovarian cancer and that side effects resulting in cessation of oral contraceptive use shortly after it was begun may be indicative of factors that are protective against the disease. PMID- 1415132 TI - Leukocyte count and risk of major coronary heart disease events. AB - The association between leukocyte count and subsequent risk of major coronary heart disease events was examined using data from three prospective cohort studies--two from the United States and one from Great Britain. A total of 28,181 middle-aged men were followed for 6-12 years. A total of 1,768 men had a nonfatal myocardial infarction or died of coronary heart disease. In all three cohorts, there was a positive, statistically significant relation between baseline leukocyte count and risk of subsequent major coronary heart disease events after adjustment for age, serum total cholesterol, diastolic blood pressure, and number of cigarettes smoked per day (relative odds = 1.32 (p less than 0.0001), 1.15 (p = 0.0001), and 1.14 (p = 0.003), corresponding to a 2,000/mm3 difference in leukocyte count). The associations persisted when all nonsmokers (former smokers plus never smokers) and never smokers alone were considered and when those with evidence of preexisting coronary heart disease at baseline were excluded. Leukocyte count appears to be an indicator of a person's future risk of major coronary heart disease events. PMID- 1415133 TI - Incidence of cancer in Norwegian workers potentially exposed to electromagnetic fields. AB - The risk of cancer was investigated in a cohort of 37,945 male Norwegian electrical workers for whom information on job description was collected from 1960 census data and linked to the 1970 census data. The standardized incidence ratio was calculated for all cancer sites in the overall cohort by comparison with national incidence rates for economically active men at the 1960 census. The standardized incidence ratios for cancers of the breast, pleura (mesothelioma), larynx, and bladder and for soft tissue sarcoma were elevated, while those for non-Hodgkins and Hodgkins lymphoma were lower. The standardized incidence ratio for leukemia for electrical workers with 10 or more economically active years was 1.41. The standardized incidence ratio for brain tumors in this subgroup of electrical workers was 1.14. These results from a large, national, population based study at the Cancer Registry of Norway give support to previous findings of a possible association between electrical work and the risk of leukemia. PMID- 1415134 TI - Occupation and bladder cancer risk. AB - This study examines the estimated risk of bladder cancer associated with various occupations among 1,465 cases identified in Orange County, California, during 1984-1988. The annual age-adjusted incidence rate per 100,000 population in Orange County was similar to that of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute: 25.7 in males and 6.2 in females. Cases were compared with a sample of Orange County residents relative to broad category of current occupation, adjusted for age and cigarette smoking. The estimated relative risks were significant for males in machine trades (relative risk (RR) = 2.69, 95% confidence interval (CI) 1.24-5.82) and processing occupations (RR = 5.77, 95% CI 1.43-23.27) and for females in machine trades (RR = 8.34, 95% CI 1.14-61.17) and homemakers (RR = 5.37, 95% CI 2.40-11.99) as compared with individuals of the same sex in professional, technical, and managerial occupations. PMID- 1415135 TI - Relations over time between psychiatric and somatic disorders: the Stirling County Study. AB - A longitudinal study of a general population in Atlantic Canada provided information on associations between two broad categories of illness: somatic disorders and disorders involving depression and/or anxiety. Prevalence was investigated in a sample of 1,003 adults selected in 1952 and another sample of 1,094 adults selected in 1970. Using a cohort of 618 survivors from the 1952 sample who were followed up in 1968, the authors studied prevalence at the beginning and end of the 16-year period. Incidence was also investigated so that the strength of associations between prior illness of one type and subsequent illness of the other type could be assessed. Data were obtained by interviewing subjects with the same structured schedule at each time of investigation. In prevalence enumerations, psychiatric disorders were found to be significantly associated with somatic disorders. Prior somatic disorder was significantly associated with subsequent incidence of depression and/or anxiety and vice versa. The results did not, however, show one direction of influence ("psyche-to-soma" or "soma-to-psyche") to be markedly stronger than the other. The results mainly support the concept of "generalized vulnerability" and draw attention to the importance of recognizing comorbidity in diagnosis and clinical practice. PMID- 1415136 TI - Confounding in studies of adverse reactions to vaccines. AB - Several social and medical attributes are associated with both avoidance or delay of vaccination and an increased risk of adverse events such as sudden infant death syndrome or childhood encephalopathy. Studies that fail to control adequately for such confounding factors are likely to underestimate the risks of adverse events attributable to vaccination. This paper reviews the literature on studies of severe adverse events after the administration of pertussis antigen containing vaccines, with particular attention to the measures taken by different investigators to avoid this problem. Most published studies have reported a deficit of sudden infant death syndrome among vaccinees, which may reflect confounding in their study designs. An expression is derived to explore the extent of underestimation that may be introduced in such studies, under different sets of conditions. Confounding of this sort is a general problem for studies of adverse reactions to prophylactic interventions, as they may be withheld from some individuals precisely because they are already at high risk of the adverse event. PMID- 1415137 TI - Hostility and health behaviors in young adults: the CARDIA Study. Coronary Artery Risk Development in Young Adults Study. AB - Hostility has been associated with coronary heart disease mortality. To assess possible mechanisms linking hostility to coronary heart disease risk, the authors conducted analyses in a cross-sectional study from data collected in 1985 and 1986 on 5,115 young adults, aged 18-30 years, black and white, male and female, in four large urban areas of the United States. The results show that higher levels of hostility as determined by the Cook-Medley Hostility Scale were strongly associated with tobacco and marijuana smoking, increased alcohol consumption, and greater caloric intake in both blacks and whites and in both men and women. The increased caloric consumption was evident in the higher waist/hip ratios, particularly in men (p less than 0.05). The associations were particularly strong (p less than 0.001) for tobacco cigarette smoking and marijuana smoking, with roughly a 1.5 times higher prevalence in the top hostility quartile compared with the bottom quartile after adjusting for age and education. Hostility levels were not related to the percentage of calories from fat or from sucrose intake, to plasma cholesterol levels, or to physical fitness (except for a weak association in the latter in white women). The results describe relations between hostility and health behaviors that may be detrimental to health. The findings provide a possible explanation for the association between hostility and coronary heart disease mortality. PMID- 1415138 TI - Hostility during late adolescence predicts coronary risk factors at mid-life. AB - Hostility, as measured by the Cook-Medley Hostility Scale of the Minnesota Multiphasic Personality Inventory, has been found to predict higher rates of both coronary heart disease and all-cause mortality. To evaluate one mechanism whereby hostility might contribute to health problems, the authors used regression models to determine whether hostility measured in college (1964-1966) predicted coronary risk factors assessed 21-23 years later (1987-1990) in 4,710 men and women. Of this group, 828 had lipids measured (1988-1991). Persons with higher hostility scores in college were significantly more likely at follow-up to consume more caffeine (r = 0.043), to have a larger body mass index (r = 0.055), to have higher lipid ratios (r = 0.092), and to be current smokers (r = 0.069) than those with lower hostility scores during college. Cross-sectional analyses found significant associations of contemporaneous hostility scores with the same four risk factors, as well as with alcohol consumption and hypertension (rs ranging from 0.043 to 0.117). These associations are large enough to have possible public health significance. We conclude that hostility may contribute to health problems through its influences on several coronary risk factors across the adult life span. PMID- 1415139 TI - Onset and disappearance of gastrointestinal symptoms and functional gastrointestinal disorders. AB - Functional gastrointestinal disorders, including the irritable bowel syndrome, account for up to 40% of referrals to gastroenterologists, but accurate data on the natural history of these disorders in the general population are lacking. Using a reliable and valid questionnaire, the authors estimated the onset and disappearance of symptoms consistent with functional gastrointestinal disorders. An age- and sex-stratified random sample of 1,021 eligible residents of Olmsted County, Minnesota, aged 30-64 years were initially mailed the questionnaire; 82% responded (n = 835). In a remailing to responders 12-20 months later, 83% responded again (n = 690). The age- and sex-adjusted prevalence rates per 100 for irritable bowel syndrome, chronic constipation, chronic diarrhea, and frequent dyspepsia were 18.1 (95% confidence interval (CI) 15.1-21.1), 14.7 (95% CI 11.9 17.4), 7.3 (95% CI 5.3-9.3), and 14.1 (95% CI 11.5-16.8), respectively, on the second mailing. Symptoms were not significantly associated with nonresponse to the second mailing; moreover, the estimated prevalence rates were not significantly different from the first mailing. Among the 582 subjects free of the irritable bowel syndrome on the first survey, 9% developed symptoms during 795 person-years of follow-up, while 38% of the 108 who initially had the irritable bowel syndrome did not meet the criteria after 146 person-years of follow-up. Similar onset and disappearance rates were observed for the other main symptom categories. While functional gastrointestinal symptoms are common in middle-aged persons and overall prevalence appears relatively stable over 12-20 months, substantial turnover is implied by the observed onset and disappearance rates; several potential sources of bias do not seem to account for this variation. PMID- 1415140 TI - Diet and other risk factors for laryngeal cancer in Shanghai, China. AB - A population-based, case-control study of laryngeal cancer was conducted in Shanghai, China, during 1988-1990, in which 201 incident cases (177 males, 24 females) and 414 controls (269 males, 145 females) were interviewed. Cigarette smoking was the major risk factor, accounting for 86% of the male and 54% of the female cases. After adjusting for smoking, there was little increase in risk associated with drinking alcoholic beverages. Among men, cases more often reported occupational exposures to asbestos and coal dust. A protective effect was associated with the intake of fruits (particularly oranges and tangerines), certain dark green/yellow vegetables, and garlic, but there was an increased risk with the intake of salt-preserved meat and fish. The findings suggest that risk factors for laryngeal cancer in Shanghai resemble those in Western countries, and they provide further evidence that dietary factors play an important etiologic role. PMID- 1415141 TI - Dietary assessment of older Iowa women with a food frequency questionnaire: nutrient intake, reproducibility, and comparison with 24-hour dietary recall interviews. AB - The authors report the results of a dietary survey of 38,121 Iowa women, 55-69 years of age in 1986, based on a semiquantitative food frequency questionnaire previously tested among Boston-area women aged 34-59 years. The Iowa women, compared with the younger Boston-area women, consumed a similar amount of calories (1,767 vs. 1,844 kcal) and a similar amount of total calories from fat (35 vs. 37%) but had markedly greater intake of the following micronutrients after including supplement use: iron (+18%), calcium (+33%), vitamin A (+43%), riboflavin (+46%), thiamine (+50%), and pyridoxine (+122%). The reproducibility of the questionnaire was examined in two more administrations to 44 of the Iowa women in January and June of 1988. Reproducibility was highest for alcohol (Pearson's r = 0.99), caffeine (r = 0.95), and vitamin E (r = 0.90) and lowest for sucrose (r = 0.53), polyunsaturated fat (r = 0.56), and iron (r = 0.59). Micronutrient intakes were generally more reproducible than macronutrient intakes. The agreement between the June 1988 questionnaire and the average of five 24-hour dietary recalls was also assessed in the 44 subjects. The median correlations of energy-adjusted intake were as follows: for macronutrients, r = 0.45; for micronutrients without supplements, r = 0.33; and for micronutrients with supplements, r = 0.64. This food frequency questionnaire appears to be reasonably reproducible and accurate, so that its use may be extended to epidemiologic studies of older women with a broad range of socioeconomic backgrounds. PMID- 1415142 TI - Childhood weight and growth rate as predictors of adult mortality. AB - The effect of rate of growth and relative weight in childhood on adult mortality was studied among 13,146 persons whose weights and heights were measured between the ages of 5 and 18 years in Hagerstown, Maryland, during the period 1933-1945. Relative weight was defined internally, age- and sex-specific Z-scores for height and weight were calculated using national standards, and height and weight velocities were measured as annual increments. Associations between growth parameters (pre- and postpubertal) and mortality through 1985 were investigated in subjects who matched the 1963 and 1975 private health censuses of Washington County, Maryland, using a nested case-control design. Odds ratios of mortality increased linearly with prepubertal relative weight (p less than 0.05 for both sexes combined) and with postpubertal relative weight in females (p less than 0.01). The associations between growth velocities or attained height with mortality tended to be inverse, although not statistically significant. These results are compatible with the existence of positive associations of overweight in school-age children with long-term mortality and seem to allay fears that harm could come from increased growth rates in childhood. Without jeopardizing growth, the avoidance of overweight in childhood might reduce mortality in middle age. PMID- 1415143 TI - The predisposing and protective factors against dengue virus transmission by mosquito vector. AB - An outbreak of dengue fever occurred in Taiwan between 1987 and 1988. The highest attack rate among adults was estimated at 5.6% in the city of Kao-hsiung. A case control study was carried out to determine the risks of contracting dengue infection and to identify protective factors against the infection. One hundred dengue patients of the authors' hospital who were diagnosed by virologic or serologic tests constituted the case group. Each dengue patient was matched to a control patient of the same age and sex who had been diagnosed as suffering from a non-vector-borne disease on the same day as the dengue patient. Of the household protective measures against dengue infection prior to the occurrence of illness, the adjusted odds ratio, estimated by stratified analysis, was lower for people who lived in screened houses (odds ratio = 0.58, 95% confidence interval 0.36-0.92) as compared with inhabitants of unscreened houses. The odds ratio was as low as 0.18 (95% confidence interval 0.06-0.56) for people whose homes were fully screened with door screens opening outwardly. Patients who lived near markets and/or open sewers or ditches were running a risk of dengue infection 1.8 (95% confidence interval 1.3-2.4) times higher than those who lived elsewhere. To control dengue outbreaks, the authors recommend that special attention should be devoted to the reduction of outdoor vector sources. Full screening, especially outwardly opening screen doors, seems to be an individual's best protection against dengue fever. PMID- 1415144 TI - Risk factors for invasive Haemophilus influenzae type b in Los Angeles County children 18-60 months of age. AB - Potential factors that confer risk or protection for invasive Haemophilus influenzae type b disease were evaluated in Los Angeles County children 18-60 months of age by case-control methods. In this age group, 79 H. influenzae type b cases were identified by overlapping surveillance methods, and 221 random controls were selected by random digit dialing. Cases and controls were similar in sex, prior health, proportion attending day care, parental educational level, history of breast feeding, and proportion vaccinated with measles/mumps/rubella vaccine. The effect of H. influenzae type b vaccination was controlled in all analyses, and results of vaccine efficacy have been reported elsewhere. Cases were more likely to have a significant underlying medical condition, reside in home with more than six residents, have a lower yearly household income, have two or more smokers in the home, and to be black. Using conditional logistic regression models, the following were significant independent risk factors after adjusting for age, month of diagnosis, H. influenzae type b vaccine status, and the other factors: 1) more than two smokers in the house (odds ratio (OR) = 6.00; 95% confidence interval (CI) 1.49-24.06); 2) household size of more than six persons (OR for more than six vs. less than three persons = 3.71; 95% CI 1.10 12.60); and 3) black maternal race (OR for black vs. Hispanic = 3.47; 95% CI 1.41 8.53). We conclude that exposure to smoking in the home, living in households with more than six members, and the black race are each independently associated with an increased risk for H. influenzae type b disease in Los Angeles County children and, when combined, constitute a major reason for H. influenzae type b disease occurrence. PMID- 1415145 TI - The harm reduction approach and risk factors for human immunodeficiency virus (HIV) seroconversion in injecting drug users, Amsterdam. AB - To assess risk factors for seroconversion to human immunodeficiency virus, the authors studied a cohort of human immunodeficiency virus-seronegative injecting drug users in Amsterdam, the Netherlands, between December 1985 and November 1991. The behaviors of 31 seroconverters were compared with those of 202 seronegative injecting drug users (controls). Three independent risk factors for seroconversion were found in logistic regression: 1) living greater than 10 years in Amsterdam (odds ratio (OR) = 2.45, 95% confidence interval (CI) 1.09-5.53); 2) first injection less than or equal to 2 years ago (OR = 3.43, 95% CI 1.20-9.81); and 3) injecting mainly at home (OR = 0.39, 95% CI 0.18-0.88). No evidence was found that receiving daily methadone treatments at methadone posts and obtaining new needles/syringes via the exchange program were protective. However, the data suggest that exchanging needles may have been protective at the start of this program. Influencing injecting drug users to modify behavior to prevent new infections appears to be very difficult, and it may, therefore, be important to increase preventive efforts targeted at the sexual partners of injecting drug users. PMID- 1415146 TI - Issues in human immunodeficiency virus (HIV) screening programs. AB - Unlike test sensitivity and specificity, the false positive and negative predictive values (probabilities of mislabeling an individual being tested) depend heavily on the prevalence of the infection of the human immunodeficiency virus (HIV) as well as the quality of the kit. A consequence of this dependence is that the false positive predictive value can reach a high magnitude such as 0.9; that is, 90% of the positive tests are false. This raises many important issues pertaining to the current practice of HIV screening such as to how to control these misclassification errors, how to interpret test results, and how to estimate prevalence using test results. These issues are examined in detail here by considering the factors that dictate the quality of a screening program. Some real data examples are used to illustrate the importance of this consideration in designing programs to achieve the desired goals. The rationale behind the common two-step sequential protocol in HIV screening is examined to point out its limitations under practical situations. Finally, the use of entropy in evaluating the informativeness of a screening program is discussed. PMID- 1415147 TI - Joint influence of fat and lean body composition compartments on femoral bone mineral density in premenopausal women. AB - Body composition (fat and lean compartments) and bone mineral density were measured in 246 healthy premenopausal women, aged 20-40 years, residing in Tecumseh, Michigan. Body composition was measured using four-point bioelectrical impedance and values for fat and lean compartments categorized into tertiles. Additionally, each woman was classified into one of nine different cells based on her location within a 3 x 3 table which reflects the joint distribution of both fat and lean compartments. Bone mineral density of the proximal femur, including the femoral neck and trochanter, was measured using dual photon densitometry. The mean femoral neck bone mineral density values increased significantly and linearly for each tertile of muscle mass (0.90, 0.95, and 1.02 g/cm2, p less than 0.0002). Femoral bone mineral density increased significantly but not linearly as the fat compartment progressed from the lowest to the highest tertile (0.95, 0.93, and 0.99 g/cm2). Bone mineral density of the proximal femur was similar and significantly greater in the high muscle/low fat and high muscle/high fat body composition subgroups compared with bone mineral density in the seven other groups. However, women in the high muscle/low fat subgroup had substantially lower mean weight (67 vs. 91 kg, p less than 0.0001) and mean Quetelet index (22.1 vs. 33.7 kg/m2, p less than 0.0001) than women in the high muscle/high fat subgroup. Bone mineral density values were similar and significantly lower in the following body composition cells: low muscle/low fat, low muscle/medium fat, and low muscle/high fat. Similar findings were observed at the trochanteric site. Low muscle is a risk factor for low bone mineral density in young adult women while higher fat is protective only when associated with substantial muscle. PMID- 1415148 TI - Preterm delivery and low birth weight among first-born infants of black and white college graduates. AB - Reproductive outcomes were investigated in black and white female college graduates, presumed to be of similar socioeconomic status and similar risk profile with respect to environmental factors. Data were gathered by mail survey from graduates (1973-1985) of four Atlanta, Georgia, colleges between February and June 1988. Of 6,867 alumnae to whom questionnaires were mailed, 3,084 responded. A follow-up study of black nonrespondents yielded responses from 14% (335) of those who did not respond to the mail survey. For all graduates with a first live born at the time of survey (n = 1,089), the rates of preterm delivery, low birth weight, and infant mortality were 80.8, 82.6, and 14.6 per thousand births (primigravida), respectively. Compared with white graduates, black graduates had 1.67 times the risk of preterm delivery and 2.48 times the risk of low birth weight. Measures of social and economic status differed significantly by race. However, adjustment for these variables did not reduce the estimated risk for black graduates compared with whites. Analysis of the nonresponder survey suggested that respondent data alone overestimates the incidence of adverse outcomes in blacks; using nonresponder data, relative risks of 1.28 (preterm delivery) and 1.75 (low birth weight) were calculated as lower limits of the increased risk for blacks. PMID- 1415149 TI - Infant resuscitation is associated with an increased risk of left-handedness. AB - The etiology of left lateral preference is not well understood, but some studies have suggested that it can be caused by complications at birth. The authors used data from the Child Health and Development Study, a large prospective study of pregnancy and child development conducted 1959-1966 in the San Francisco Bay Area of California, to examine the association between specific birth stressors and hand and foot preference. The study population consisted of 6,968 5-year-olds with no severe congenital abnormalities, and the authors controlled for potential demographic confounders and familial left-handedness. Infants who required resuscitation after delivery or who were twins or triplets were about twice as likely to demonstrate left hand preference at age 5 years (odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.3-2.5, and OR = 2.2, 95% CI 1.2-4.0, respectively). Left-footedness was also significantly associated with the same stressors. No other individual stresses were significantly associated with left lateral preference, and a composite measure indicated only a weak association. Although males, blacks, and those with left-handed siblings are more likely to show left lateral preference, these variables do not confound the association between birth stress and left lateral preference. These results indicate that specific types of birth stress are strongly associated with left hand and foot preference; however, much of the left laterality in non-clinical populations remains unexplained. PMID- 1415150 TI - Allergy and cancer: organ site-specific results from the Adventist Health Study. AB - The relation between allergy and risk of cancer was evaluated in a cohort study of 34,198 Seventh-day Adventists in California. Information on prevalence of asthma, hay fever, and reactions to chemicals, medications, bee stings, and poison oak (or ivy) was obtained by questionnaire in 1976. The reported allergies must have been serious enough to require treatment by a physician. The cohort was then followed for 6 years (1977-1982). Both stratified analysis and Cox proportional hazards regression analyses were utilized to evaluate the relation of allergy to cancer after taking into account several potentially confounding variables. For all cancer sites combined in males, there was a 33% increased risk associated with reaction to medications. In contrast, among females, reaction to medications was associated with a 21% decrease in risk. Both results were statistically significant. Prostate and breast cancer risk were elevated in persons who reported any type of allergic history, as was risk of lymphatic or hematopoietic cancers and sarcoma. For each of these types of cancer, risk increased with increasing numbers of allergies. However, ovarian cancer risk was decreased in persons with any allergic history and increasing numbers of allergies was associated with decreasing risk of this form of cancer. These results suggest that the association between allergy and cancer is complex and depends on the specific allergy and the specific organ site under consideration. PMID- 1415152 TI - Interpretation and estimation of vaccine efficacy under heterogeneity. AB - Interpretation and estimation of vaccine efficacy is complicated when the vaccine effect is heterogeneous across vaccinated strata. If a person has a certain susceptibility, or probability of becoming infected conditional on a specified exposure to infection, then one effect of a vaccine would be to reduce that susceptibility, possibly to zero. Vaccine efficacy is a function of the relative susceptibilities in the vaccinated and unvaccinated persons. Under heterogeneity of vaccine effect, a general expression for a summary vaccine efficacy parameter is a function of the vaccine efficacy in the different vaccinated strata weighted by the fraction of the vaccinated subpopulations in each stratum. Interpretation and estimability of the summary vaccine efficacy parameter depends on whether the strata are identifiable, and whether the heterogeneity is host- or vaccine related. Bounds are derived for the summary vaccine efficacy when the strata are not identifiable for the case of an outbreak of an acute infectious disease. The upper bound assumes that everyone is equally affected by the vaccine, and the lower bound assumes that some are completely protected while others have no protection. The biologic interpretation of the two bounds is different. PMID- 1415151 TI - Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly. AB - During the winter of 1989-1990, influenza type A(H3N2) circulated widely, causing excess morbidity and mortality nationwide. From November through April, 1989 1990, hospitalized cases of pneumonia and influenza occurring among noninstitutionalized individuals 65 or more years of age were identified by 20 acute care hospitals in southern lower Michigan. These cases were group matched on age, sex, race, and zip code to randomly sampled, community-based controls from a comprehensive listing of Medicare beneficiaries residing in the study area. Self-reported data were collected from cases and controls on influenza vaccine status for the 1989-1990 season and on a number of other factors which could have influenced vaccination status or outcome. Questionnaires were completed by 1,907 individuals, 449 of whom were cases, resulting in an overall response rate of 76%. A community-based influenza surveillance system was implemented to determine the timing and intensity of viral activity and influenza like illness. Vaccine effectiveness in preventing overall pneumonia and influenza hospitalizations was estimated by logistic regression. During the 3-month period of surveillance-confirmed peak influenza type A(H3N2) circulation, vaccine effectiveness was 45% (95% confidence interval 14-64, p = 0.009). However, during the 3-month period of low or absent virus activity, identical methodology and model specification resulted in an effectiveness estimate of 21% that was not statistically different from zero (p = 0.36). The effectiveness determined during the peak period of virus circulation is felt to be a conservative estimate, since agents other than influenza are responsible for pneumonia and influenza hospitalizations, even during times of peak influenza activity. PMID- 1415153 TI - Variation and covariates of the number of benign nevi in adolescents. AB - Melanocytic nevi of diameter greater than or equal to 2 mm were counted on most of the skin surface of 349 adolescents aged 14-15 years of European race or ethnicity in Dunedin, New Zealand. Total counts are described by means of a form of Poisson-error log-linear modeling suitable for data showing unexplained variation (NE Breslow, Appl Statist 1984;33:38-44). There were marked interpersonal variation in the number of nevi; only some was attributable to observed factors. The mean and median counts were 23.8 and 18 nevi, respectively. The estimated ratio of the number of nevi for females compared with males was 0.7 (95% confidence interval (CI) 0.6-0.8). Greater amounts of sunbathing were associated with greater numbers of nevi. Hair and eye color, socioeconomic status, and sunburn history did not show statistically significant effects. Time since menarche and shaving status also showed no effects. Lack of suntan was associated with lower counts. Freckling was positively correlated with higher counts; the severe freckling group had an estimated ratio of 1.9 (95% CI 1.3-2.8) compared with those with no or very few freckles. The results are consistent with the hypothesis that ultraviolet radiation exposure from recreational sun exposure positively influences the total burden of nevi in normal subjects. Comparison with other epidemiologic studies suggests that the typical ultraviolet radiation dose-nevus yield curve might be steeper in males than females. Unexplained variation of nevus count may reflect heterogeneity of constitutional factors not yet measured in epidemiologic studies. PMID- 1415154 TI - Effect of nondifferential misclassification on estimates of odds ratios with multiple levels of exposure. AB - Nondifferential misclassification of exposure status with a dichotomous exposure will produce biased estimates of odds ratios such that the misclassified odds ratio is always biased toward the null value. However, when an exposure classification has more than two levels, empirical data indicate that the direction of bias is less predictable. Analysis of an algebraic model of multi level exposure misclassification reveals that all odds ratios based on the misclassified data are constrained between the nonmisclassified odds ratio for the most extreme category and the inverse of this value. This implies that the misclassified odds ratio for the most extreme exposure level will be biased toward the null but that odds ratios for intermediate levels of exposure could be biased away from the null value. Further, the amount of bias depends not only on the misclassification rates but also on the distribution of subjects across exposure levels. If it is assumed that misclassification is likely to occur only between adjacent categories, the range of possible misclassified odds ratios is reduced but is still sufficient to permit serious distortion of an exposure response relation. In general, biases away from the null occur only for intermediate levels of exposure. Reversal of an exposure-response relation is more likely to occur when misclassification rates are high (especially between nonadjacent levels) and when the number of exposure levels is low. PMID- 1415155 TI - Re: "Polycystic ovaries and the risk of breast cancer". PMID- 1415156 TI - Re: "Guillain-Barre syndrome and influenza vaccination in the US Army, 1980 1988". PMID- 1415157 TI - Birth defects in Norway by levels of external and food-based exposure to radiation from Chernobyl. AB - In Norway, external doses of radiation resulting from fallout from the Chernobyl nuclear accident were estimated from detailed measurements, including soil deposition patterns. Internal doses were estimated from measurements of radioactive cesium in meat and milk supplies. The doses were calculated as average monthly doses for each of 454 municipalities during 36 consecutive months after the accident in spring 1986. Prospectively collected data on all newborns listed in the Medical Birth Registry of Norway who were conceived in the period May 1983-April 1989 were used to assess possible dose-response relations between estimated external and food-based exposures and congenital malformations and some other conditions. A positive association was observed between total radiation dose (external plus food-based) and hydrocephaly, while a negative association was observed for Down's syndrome. However, an important conclusion of the study was that no associations were found for conditions previously reported to be associated with radiation, i.e., small head circumference, congenital cataracts, anencephaly, spina bifida, and low birth weight. Potential sources of bias, including exposure misclassification and incomplete ascertainment of cases, are discussed. PMID- 1415158 TI - Mortality among workers exposed to polychlorinated biphenyls. AB - On the basis of evidence from animal studies, polychlorinated biphenyls (PCBs) are considered potentially carcinogenic to humans. However, the results of studies in human populations exposed to PCBs have been inconsistent. The authors conducted a retrospective cohort analysis (1957-1986) comparing the mortality of 3,588 electrical capacitor manufacturing workers with known exposure to PCBs with age-, sex-, and calendar time-specific mortality rates for all whites in the United States. Proportional hazards modeling was also performed to examine the association between cumulative PCB exposure and site-specific cancer mortality. All-cause mortality (192 deaths observed, 283.3 expected) and total cancer mortality (54 deaths observed, 63.7 expected) were lower than expected. More deaths were observed than expected for malignant melanoma (8 observed, less than 2.0 expected) and cancer of the brain and nervous system (5 observed, 2.8 expected). The average estimated cumulative dose for the cases of brain cancer (22.9 units) was greater than for other workers (12.9 units), but the 95% confidence intervals around this difference were broad. The risk of malignant melanoma was not related to cumulative PCB exposure. These results provide some evidence of an association between employment at this plant and malignant melanoma and cancer of the brain. The possibility that the results are due to chance, bias, or confounding cannot be excluded. PMID- 1415159 TI - Influence of paternal characteristics on the risk of low birth weight. AB - The combined effects of maternal and paternal factors on the risk of delivering low birth weight (less than 2,500 g) and very low birth weight (less than 1,500 g) infants were examined among married parents. Using 1984-1988 natality data compiled by the National Center for Health Statistics, the authors found paternal education and race to have independent effects on the risks of low birth weight and very low birth weight after adjustment for maternal characteristics. The odds of low and very low birth weight decreased with increasing paternal education. Adjustment for paternal education decreased the effect of maternal education on the risks of low and very low birth weight. Additionally, the examination of paternal race led to the identification of a subgroup of married black women with lower risks of low and very low birth weight than married black mothers overall. These data suggest that paternal characteristics should be used, in addition to maternal characteristics, to describe the risks of low and very low birth weight. PMID- 1415160 TI - Reproductive factors and risk of myocardial infarction. AB - The relation of reproductive factors to risk of myocardial infarction in women aged 45-69 years was examined in a case-control interview study carried out in Massachusetts from 1986 to 1990. Each of 858 cases of first myocardial infarction was age-matched with a control from the same precinct of residence. Conditional logistic regression was used to control the matching factors and the major known and suspected risk factors for coronary heart disease. For parous women compared with nulliparous women, the estimated relative risk of myocardial infarction was 1.8 (95% confidence interval (CI) 1.0-3.3). Among parous women, the relative risk estimate for five or more births relative to fewer births was 1.4 (95% CI 1.0 2.0); the estimate for a first birth before age 20 relative to a later age at first birth was 1.7 (95% CI 1.1-2.6). The greatest increase in risk was observed for women who had both an early age at first birth and five or more children. However, confounding by factors related to socioeconomic status may have contributed to the results. Compared with women who had a natural menopause at age 50 or older, women who reached the menopause before age 45 were at increased risk regardless of type of menopause: The estimated relative risks were 2.1 (95% CI 1.3-3.2), 1.7 (95% CI 1.0-2.7), and 1.7 (95% CI 1.0-2.8) for early natural menopause, bilateral oophorectomy, and hysterectomy with retention of one or both ovaries, respectively. These results suggest that early cessation of ovulatory function, whether due to natural causes or to surgery, increases the risk of myocardial infarction. Age at menarche was not related to myocardial infarction risk. PMID- 1415161 TI - Ingested arsenic, keratoses, and bladder cancer. AB - A cohort of 478 patients treated with Fowler's solution (potassium arsenite) in Lancashire, England, during the period 1945-1969 and previously followed until January 1, 1980, was followed for an additional 11 years. A significant excess of bladder cancer mortality occurred (observed/expected ratio = 5/1.6; p = 0.05). No excess was found for other causes of death. In a subcohort of 142 patients examined for signs of arsenicism around 1970, all 11 subsequent cancer deaths occurred in those with signs of arsenicism (p = 0.0009). PMID- 1415162 TI - Reduced cancer morbidity and mortality in a prospective cohort of women with distal forearm fractures. AB - At the Department of Orthopedics of University Hospital, Lund, Sweden, cancer incidence and overall and cause-specific mortality were studied in a prospective cohort of 677 women who had experienced a fracture of the distal forearm in 1974 or 1975. The women were followed through population-based population, cancer, and death registries in southern Sweden. There was a significant reduction in overall cancer incidence (66 cases observed vs. 90.21 expected), breast cancer incidence (11 cases observed vs. 20.31 cases expected), and incidence of tumors of the female genital tract (5 cases observed vs. 11.84 expected). Overall mortality was also reduced (146 cases observed vs. 191.69 cases expected), and rates of death from circulatory disease (79 cases observed vs. 111.49 expected) and malignant tumors (30 cases observed vs. 40.41 expected) were both lower than expected. PMID- 1415163 TI - Blood pressure and twenty-year mortality in the city of Bergen, Norway. AB - A blood pressure survey was carried out in 1963 in the city of Bergen, Norway. The relation between 20-year mortality and blood pressure in 52,064 participants aged 30-89 years at examination was analyzed. Increased blood pressure was related to increased mortality from coronary heart disease, stroke, and all causes in all age groups except the oldest, where a more irregular pattern was present. The relative risks decreased with age at screening, while the absolute increase in mortality with increasing blood pressure was greatest in persons aged 60-69 or 70-79 years at screening. A log-linear relation between systolic blood pressure and coronary heart disease and stroke mortality was seen in both men and women. An upturn in total mortality at low systolic blood pressures was suggested in the groups aged 60 years or more at screening. An upturn, or leveling off, was also seen at low diastolic blood pressures for total deaths and stroke deaths in both men and women. PMID- 1415164 TI - The increase in blood pressure with age and body mass index is overestimated by conventional sphygmomanometry. AB - This cross-sectional study investigated whether the technique of blood pressure measurement used (conventional sphygmomanometry vs. ambulatory monitoring) affects the relation between blood pressure and both age and body mass index. Two independent data sets were analyzed. The first comprised 328 subjects (48% men) drawn from the population of a small Belgian town, and the second comprised 776 Irish bank employees (51% men). Age ranged from 17 years to 81 years, and body mass index (weight (kg)/height (m)2) ranged from 16.6 to 40.2. Twenty-four-hour ambulatory blood pressure was lower than blood pressure measured by a nurse in both the Belgian population sample (118/71 mmHg vs. 122/73 mmHg) and the Irish employees (118/72 mmHg vs. 119/76 mmHg). When blood pressure was measured by an observer, the well-established relations between systolic and diastolic blood pressure and both age and body mass index were evident. When the analyses were repeated using 24-hour measurements, the increment (cross-sectionally assessed) in blood pressure with age was weaker, especially in young and middle-aged subjects (20-60 years), while the increase in blood pressure with body mass index was also reduced. The within-subject differences between the conventional and ambulatory blood pressure measurements increased with older age and greater body mass index. Several other relations with blood pressure as the response variable may require revision in light of the present findings. PMID- 1415165 TI - The risk approach to intervention in severe malnutrition in rural Bangladesh. AB - To determine whether clinical marasmus occurs in small groups of children from easily recognizable high-risk households, the authors conducted a case-control study to identify risk indicators that may be used in targeted interventions. Cases were children whose mid-upper arm circumference measured less than 110 mm, and controls were children matched for age and sex with arm circumferences greater than 120 mm. Between June 1988 and June 1989, 164 such pairs of children aged 1-4 years were studied in Matlab, Bangladesh. Conditional logistic regression analysis showed an increased risk of marasmus among children from families with other children under 5 years of age (odds ratio = 2.80, 95% confidence interval 1.56-5.02) and children who consumed formula foods (odds ratio = 18.81, 95% confidence interval 4.15-85). Higher maternal education was associated with reduced risk of marasmus. Further examination of these risk indicators suggests that the resources saved through targeting fewer households will be negated by missing many children with marasmus. The authors conclude that the application of targeted interventions against marasmus, using the risk approach, is unlikely to be efficient. PMID- 1415166 TI - Efficiency loss from categorizing quantitative exposures into qualitative exposures in case-control studies. AB - In the analysis of data from case-control studies, quantitative exposure variables are frequently categorized into qualitative exposure variables, such as quarters. The qualitative exposure variables may be scalar variables that take the median values of each quantile interval, or they may be vectors of indicator variables that represent each quantile interval. In a qualitative analysis, the scalar variables may be used to test the dose-response relation, while the indicator variables may be used to estimate odds ratios for each higher quantile interval versus the lowest. Qualitative analysis, implicitly and explicitly documented by many epidemiologists and biostatisticians, has several desirable advantages (including simple interpretation and robustness in the presence of a misspecified model or outlier values). In a quantitative analysis, the quantitative exposure variables may be directly regressed to test the dose response relation, as well as to estimate odds ratios of interest. As this paper demonstrates, quantitative analysis is generally more efficient than qualitative analysis. Through a Monte Carlo simulation study, the authors estimated the loss of efficiency that results from categorizing a quantitative exposure variable by quartiles in case-control studies with a total of 200 cases and 200 controls. In the analysis of the dose-response relation, this loss is about 30% or more; the percentage may reach about 50% when the odds ratio for the fourth quartile interval versus the lowest is around 4. In estimating odds ratios, the loss of efficiency for the second, third, and fourth quartile intervals versus the lowest is around 90%, 75%, and 40%, respectively. The authors consider the pros and cons of each analytic approach, and they recommend that 1) qualitative analysis be used initially to estimate the odds ratios for each higher quantile interval versus the lowest to examine the dose-response relation and determine the appropriateness of the assumed underlying model; and 2) quantitative analysis be used to test the dose-response relation under a plausible log odds ratio model. PMID- 1415167 TI - A multistate outbreak of sporotrichosis associated with sphagnum moss. AB - In the spring of 1988, the largest documented US outbreak of cutaneous sporotrichosis to date occurred, with 84 cases among persons from 15 states who were exposed to Wisconsin-grown sphagnum moss used in packing evergreen tree seedlings. In New York State, 13 cases occurred among 109 forestry workers. All 13 cases occurred among 76 workers who had handled evergreen seedlings and moss (attack rate = 17%). For those exposed to evergreens and moss, the risk of infection increased as worktime exposure to moss increased (attack rates: less than 10 hours, 8%; 10-19 hours, 12%; greater than 19 hours, 33%). While environmental samples of moss from the Wisconsin supplier were negative, Sporothrix schenckii was cultured from multiple samples of the sphagnum moss obtained from one of six Pennsylvania tree nurseries, representing the nursery that was identified as the source for 79 (94%) of the moss-associated cases. Differences in tree-handling procedures at this nursery--including the use of 1- to 3-year-old moss to pack seedlings, use of a pond water source to wet the moss, use of an organic polymer gel on the seedling root system, and underground storage and longer storage of moss-packed seedlings before shipping--suggested possible explanations for the association. Efforts to prevent sporotrichosis among persons handling evergreen seedlings should include the use of alternate types of packing material (e.g., cedar wood chips or shredded paper) and protective clothing such as gloves and long-sleeved shirts. PMID- 1415168 TI - Interspecies transmission and reassortment of influenza A viruses in pigs and turkeys in the United States. AB - Genetic reassortment between influenza A viruses in humans and in animals and birds has been implicated in the appearance of new pandemics of human influenza. To determine whether such reassortment has occurred in the United States, the authors compared the genetic origins of gene segments of 73 swine influenza virus isolates (1976-1990), representing 11 states, and 11 turkey virus isolates (1980 1989), representing eight states. The host origin of gene segments encoding the internal proteins of H1N1 swine and turkey influenza viruses was identified by developing a dot-blot assay. All gene segments of swine influenza viruses were characteristic of influenza virus genes from that species, indicating that pigs may not be frequent participants in interspecies genetic exchange and reassortment of influenza viruses in the United States. In contrast, 73% of the turkey influenza virus isolates contained genes of swine origin. One turkey isolate was a reassortant having three genes characteristic of avian influenza virus and three of swine origin. These findings document a high degree of genetic exchange and reassortment of influenza A viruses in domestic turkeys in the United States. The molecular biologic techniques used by the authors should aid future epidemiologic studies of influenza pandemics. PMID- 1415169 TI - Re: "Completeness of the discharge diagnoses as a measure of birth defects recorded in the hospital birth record". PMID- 1415170 TI - Re: "Decline in incidence of epidemic glucose intolerance in Nauruans: implications for the 'thrifty genotype'". PMID- 1415171 TI - Re: "Race, family income, and low birth weight". PMID- 1415172 TI - Laboratory and clinical aspects of inherited thrombotic disorders. AB - The laboratory evaluation of patients with recurrent thrombosis is frequently frustrating, with a low diagnostic yield obtained despite extensive testing. The likelihood of reaching a diagnosis in these patients can be increased by considering diagnostic possibilities usually overlooked and by using assays optimal for their detection. This review summarizes clinical and laboratory issues important in inherited thrombotic disease and discusses practical aspects and a strategy for laboratory testing. New information is provided on the fibrinolytic disorders that may be a common cause of recurrent thrombosis. PMID- 1415173 TI - Inefficacy of extracorporeal photochemotherapy in the treatment of B-cell chronic lymphocytic leukemia: preliminary results. AB - Because extracorporeal photopheresis has been shown to be clinically effective in Sezary syndrome, a disease characterized by a circulating malignant clone, we initiated a pilot study of its use in B-cell chronic lymphocytic leukemia (B-CLL) to see if it could be similarly effective. We treated three patients with Rai stage III and IV B-CLL with photopheresis (3 consecutive days a week every 3 weeks) and followed serial clinical and immunologic parameters. While we noted no major toxicity, there was neither clinical response to treatment nor marked improvement in white counts or mitogen assays. We conclude that photopheresis was not effective in inducing remission in this pilot study of advanced stage B-CLL patients. PMID- 1415174 TI - Effectiveness of high-dose intravenous immunoglobulin in a case of acquired von Willebrand syndrome with chronic melena not responsive to desmopressin and factor VIII concentrate. AB - A patient with benign monoclonal IgG lambda paraproteinemia, acquired von Willebrand syndrome (AVWS), and chronic melena successfully responding to high dose intravenous immunoglobulin (lvlg) is reported. Coagulation parameters at admission were APTT (ratio) 1.68; VIII:C 11 IU/dL; vWF:Ag 7 IU/dL:Ricof less than 3 IU/dl. RIPA was greater than 1.8 mg/ml, and bleeding time (BT) was prolonged (18 min). No evidence for an in vitro inhibitor against the VIII/vWF complex was observed. VIII/vWF measurements showed a short-lived increase after both DDAVP and Hemate P, and BT was transiently normalized. After intravenous Ig (1 g/kg for 2 days), VIII/vWF measurements, hemostatic parameters and multimeric pattern were completely corrected (VIII/C 106 IU/dl, vWF:Ag 168 IU/dl, RiCof 147 IU/dl, APTT ratio 0.89, BT 5'), with a return to pre-infusion values after 15 days. Hemoccult test became negative and packed red cell transfusions, of which 130 units were administered during the last year, were no longer required. After 18 months the patient is on maintenance treatment with repeated courses of Ig, at 3 to 4-week intervals based on VIII/vWF and BT monitoring. PMID- 1415176 TI - Hand surgery in Glanzmann's thrombasthenia. PMID- 1415175 TI - A new case of acute lymphoblastic leukemia B-cell type with chromosomal rearrangements involving the T-cell receptor breakpoint at band 14q11. AB - A patient with B-cell acute lymphoblastic leukemia (ALL) and a translocation t(8;14) (q24;q11) is described. Translocation t(8;14)(q24;q32) is commonly associated with B-cell leukemia; nevertheless, translocations affecting chromosome 14 at band q11 are associated with T-cell malignancies, since the locus 14q11 contains genes that encode for the alpha and delta chains of the T cell receptor (TCR). This finding points to the idea that the association between 14q11 rearrangements and T-cell neoplasia is less than complete. PMID- 1415177 TI - 35-year-old patient with chronic myelogenous leukemia developing systemic lupus erythematosus after alpha-interferon therapy. PMID- 1415178 TI - Intravenous gammaglobulin treatment for thrombocytopenia associated with infectious diseases. PMID- 1415179 TI - Effects of zinc supplementation on somatomedin-C level, in beta thalassemia. PMID- 1415180 TI - Acquired von Willebrand's disease, IgE polyclonal gammopathy and griseofulvin therapy. PMID- 1415181 TI - Cytarabine and cardiac failure. PMID- 1415182 TI - Late febrile reaction to interferon. PMID- 1415183 TI - Changes in the lymphocyte count and lymphocyte subsets after splenectomy in human immunodeficiency virus infection. PMID- 1415184 TI - Renal toxicity in long-term alpha-interferon treatment in a patient with myeloma. PMID- 1415185 TI - Role of endothelin in disseminated intravascular coagulation. AB - We examined the changes in plasma levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, in 47 cases of disseminated intravascular coagulation (DIC) to investigate the role of ET-1 in DIC and its relation to multiple organ failure (MOF). A significant elevation of plasma levels of ET-1 was observed in some cases of DIC, especially in patients with sepsis, blastic crisis of chronic myelogenous leukemia, and cancer. However, no such significant elevation was observed in patients with acute promyelocytic leukemia (APL), acute leukemias except for APL, or non-Hodgkin lymphoma. Plasma levels of ET-1 were higher in patients with DIC with MOF than in those without MOF. Although the levels of ET-1 were decreased or remained low with clinical improvement in most DIC patients, the levels were further increased or remained high in patients who showed no improvement in DIC. It is suggested that ET-1 must play an important role in further progression of MOF with the vasoconstriction and microcirculatory disorders. PMID- 1415186 TI - 5-Aminolevulinate synthase in sideroblastic anemias: mRNA and enzyme activity levels in bone marrow cells. AB - To examine the role of 5-aminolevulinate synthase (ALAS) in the pathogenesis of sideroblastic anemias, levels of mRNAs for erythroid and housekeeping ALAS isozymes were examined, and total ALAS activity was assessed in bone marrow cells. In two patients with X-linked sideroblastic anemia the levels of mRNA for erythroid ALAS as well as for alpha and beta globin appear to be decreased while levels of mRNA for glycophorin A in both patients were the same as in normal individuals. However, amounts of housekeeping ALAS mRNA were increased two- to threefold in these patients. Total ALAS activity was also increased two- or threefold, perhaps reflecting increased transcription of the housekeeping gene in response to diminished cellular heme in erythroid cells and/or enhanced translation of the erythroid isoform in response to iron accumulation. In a third patient with X-linked sideroblastic anemia ALAS activity was low but increased to twice the normal value after pyridoxine administration, suggesting a structural defect of the enzyme. In a fourth patient, with isolated congenital, pyridoxine responsive sideroblastic anemia, the erythroid ALAS mRNA was normal and a low enzyme activity was strikingly enhanced by pyridoxal-phosphate albeit to subnormal levels. In idiopathic acquired sideroblastic anemia, ALAS mRNA for both isozymes was normal and enzyme activity was slightly elevated. These observations thus reflect heterogeneous aberrations of erythroid heme synthesis in the various types of sideroblastic anemia and suggest that defects involving erythroid ALAS underlie at least some of them. PMID- 1415187 TI - Procoagulant activity of endotoxin or tumor necrosis factor activated monocytes is enhanced by IgG from patients with lupus anticoagulant. AB - The effect of lupus anticoagulant (LA) positive plasma on the expression of human monocyte procoagulant activity (PCA) was studied. LA positive plasma were able to enhance the endotoxin or TNF alpha induced monocyte associated PCA. The monocyte PCA had the characteristic of tissue factor activity (factor VII, factor X dependence). The enhancement of monocyte PCA could be confirmed using purified LA positive IgG. The stimulating effect was supported by the F(ab')2 fragments. PMID- 1415188 TI - Dyserythropoiesis in iron-deficiency anemia: ultrastructural reassessment. AB - Iron deficiency is usually included among the causes of acquired dyserythropoiesis. This concept was derived mainly from light microscopic studies. To reassess such a notion at ultrastructural level, a transmission electron microscopic evaluation of bone marrow was performed in seven patients with iron-deficiency anemia. In contrast to the widely accepted concept, derived from light microscopic studies, only a small proportion (2-4%, not different from controls) of erythroblasts displayed some of the features of nuclear dyserythropoiesis. On the contrary, when examining the cytoplasm, we found a significantly increased number of void ropheocytotic vesicles in the majority of late erythroblasts as compared to controls (P less than 0.001). This feature may be considered as an ultrastructural marker of iron deficiency and is consistent with the present knowledge on transferrin-mediated delivery of iron to the cell. PMID- 1415189 TI - Pseudoxanthoma elasticum-like skin lesions and angioid streaks in beta thalassemia. AB - One hundred patients with homozygous or doubly heterozygous beta-thalassemia (62 with the major form and 38 with beta-thalassemia intermedia) were examined for signs of Pseudoxanthoma elasticum (PXE). Diagnostic skin lesions were found in 16 patients with either form of the basic disease. Twenty percent of all patients had angioid streaks (AS); both PXE skin lesions and AS were found in 10% of the patients; in all, 26% had either one or both of these manifestations. A positive correlation was found between the presence of one or both types of lesion and age of the patients (P = 0.032); there were no differences as regards ferritin and hematocrit levels, number of transfused units, chelation therapy, and splenic status between patients with PXE/AS findings and those without. The pathogenesis of these connective tissue manifestations at such a high frequency in beta thalassemia is not clear; the possibilities of it's being acquired or inherited are discussed, the former being considered to be the more economical interpretation. PMID- 1415190 TI - Inefficacy of intravenous immunoglobulin in patients with low-risk thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome. AB - OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG), in comparison with plasma exchange (PE), in the treatment of patients with thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). DESIGN: Prospective, nonrandomized comparative study. SETTING: Hematology department in a general hospital. PATIENTS: 17 consecutive adult patients, six of them pregnant, with diagnosis of TTP/HUS. Three had a severity score at diagnosis less than or equal to 4 and were treated with IVIG and 14 had a severity score of greater than or equal to 5 and/or were pregnant and received PE. The response was evaluated after 5 days of therapy. RESULTS: Complete remission was obtained in 0/3 cases treated with IVIG and 10/14 (71%) with PE (Fisher's exact test P = 0.05). Three patients died for widespread TTP-HUS, and four had persistent disease. In three of the four resistant patients, complete remission was obtained by further PE but not by further IVIG. The overall remission rate was 76% (13/17). CONCLUSIONS: Our study does not confirm the utility of IVIG in the management of TTP-HUS, as suggested by earlier single case reports. PMID- 1415191 TI - Influence of calcium permeabilization and membrane-attached hemoglobin on erythrocyte deformability. AB - The present study was designed to evaluate the influence of intracellular calcium [Ca]i regulated membrane attached hemoglobin (Hbm) on the deformability of human RBC and ghosts. [Ca]i of RBC was elevated via the ionophore A23187 (10 microM); the deformability of RBC and resealed ghosts was determined via measuring RBC and ghost transit times through 5 microns diameter pores with the Cell Transit Analyzer (CTA). Salient results included: (1) significantly increased RBC levels of Hbm following ionophore treatment; (2) elevated Hbm with increasing lysing medium calcium concentration (0-5 mM); (3) decreased deformability of both intact RBC and ghosts with increasing Hbm and significant (P less than 0.02 or better) linear relationships between Hbm and RBC or ghost transit times; and (4) an increased sensitivity to ionophore treatment/membrane attached hemoglobin for the higher percentiles of the CTA transit time distribution (i.e., for more rigid subpopulations). Our results thus indicate that calcium-induced interaction of hemoglobin with the RBC membrane produces cellular rheological changes; in addition, they demonstrate the usefulness of the CTA system in measuring both average RBC rheologic behavior and the distribution of cellular rheologic properties within an erythrocyte population. PMID- 1415192 TI - Treatment of acute myeloid leukemia in the elderly with low-dose cytarabine, hydroxyurea, and calcitriol. AB - Twenty-nine patients aged 62-82 years with acute myeloid leukemia (AML) were treated with a 21-day course of continuous infusion cytarabine, oral hydroxyurea, and 1,25-dihydroxyvitamin D3 (calcitriol). Ten patients had an antecedent myelodysplastic syndrome. Calcitriol was continued as the only postremission therapy. Thirteen patients (45%) obtained a complete remission, and 10 patients (34%) had a partial response for an overall 79% response rate. There were three early deaths. The median remission duration was 9.8 months. Overall median survival was 12 months for all patients and 14 months for responding patients. All responding patients had marked bone marrow hypoplasia. Twenty patients received part or all of their chemotherapy as outpatients. This regimen has acceptable toxicity and can result in prolonged remissions in elderly, high-risk patients with AML. The favorable results may be related to the synergistic effect of hydroxyurea, cytarabine, and calcitriol. PMID- 1415193 TI - Accessory spleen in recurrent chronic immune thrombocytopenic purpura. AB - From 1969 to 1985 we discovered accessory spleens in 8 patients with chronic immune thrombocytopenic purpura (ITP) who relapsed or failed after splenectomy. Imaging of accessory spleen used a liver spleen scintigraphy with heat-treated RBC labeled with Tc-99m. Platelet kinetic studies with 51Cr or 111In, including sequestration index, were performed. Five patients had accessory splenectomy. Disappearance of bleeding symptoms was achieved in the 5 splenectomized patients but with only partial response of platelet counts. These results are discussed in the context of diagnosis and therapeutic management of accessory spleens in patients with chronic immune thrombocytopenic purpura who relapsed or failed after splenectomy. PMID- 1415194 TI - Molecular basis of beta thalassemia in the south of Thailand. AB - A total of 103 beta thalassemia genes from 78 children (45 with Hb E/beta thalassemia, 8 with beta thalassemia heterozygotes, and 25 with homozygous beta thalassemia) were analyzed using dot-blot hybridization of the polymerase chain reaction-amplified DNA and direct DNA sequencing. Nine mutations were characterized in 98/103 (95%) of beta thalassemia alleles, of which six (a 4 bp deletion in codons 41-42, a G-C transition at position 5 of IVS-1, A-G transition at codon 19, an A-T transition at codon 17, an A-G transition at position -28 upstream of the beta globin gene, a G-T transition at position 1 of IVS-1), accounted for 92%. The spectrum of beta thalassemia mutations in Chinese Thai is similar to that reported among the Chinese from other parts of the world. The distribution of beta thalassemia mutations in Muslim Thai is similar to that reported among Malaysians. The most common beta thalassemia mutation in Thai and Chinese Thai patients is the frameshift mutation at codons 41-42, in comparison with the Muslim Thai in whom the G-C transition at position 5 of the IVS-1 mutation predominates. The heterogeneity of molecular defects causing beta thalassemia should aid in the planning of a prenatal diagnosis program for beta thalassemia in the South of Thailand. PMID- 1415195 TI - Leukemic manifestation in a case of alpha-chain disease with multiple polypoid intestinal lymphocytic lymphoma. AB - We describe a female aborigine from Taiwan with alpha-chain disease associated with multiple polypoid intestinal lymphocytic lymphoma and leukemic manifestation. Initially, the patient experienced intermittent diarrhea, abdominal pain, and leukemic manifestation. No evidence of bone marrow involvement was found. Alpha-chain protein was demonstrated in the serum. Gastroendoscopy and a series of radiographs of the small intestine revealed multiple polypoid tumors involving the entire length of the small intestine. Duodenal biopsy showed diffuse lymphocytic lymphoma. Immunohistochemical staining of tumor samples revealed features typical of alpha-chain disease. Cytogenetic analysis showed the same abnormal karyotypes of neoplastic clones in intestinal tumor cells and in circulating leukemic cells. The data suggest that alpha-chain disease can present initially with intestinal multiple polypoid lymphocytic lymphoma and leukemic manifestation without evidence of bone marrow involvement. The data also support the homing theory of lymphomas from mucosa-associated lymphoid tissue. PMID- 1415196 TI - Acute myelogenous leukemia: proliferation stop or cell lysis during the first hours of treatment? PMID- 1415198 TI - Influence of clinical and histological features on actuarial renal survival in adult patients with idiopathic IgA nephropathy, membranous nephropathy, and membranoproliferative glomerulonephritis: survey of the recent literature. AB - The most recent studies, using the actuarial life-table technique, of the problem of long-term renal outcome and the factors that influence it in adult patients with one of the three most common types of chronic idiopathic immune complexes mediated glomerulonephritis (IgA nephropathy [IgAN], membranous nephropathy [MN], and type I membranoproliferative glomerulonephritis [MPGN]) are reviewed. In the last decade, renal survival 10 years after onset has become similar to adult patients with idiopathic IgAN (80% to 87%) and idiopathic MN (75% to 83%), because of improvement of the renal survival of patients with MN. Renal survival at 10 years is worse for adult patients with idiopathic type I MPGN (60% to 64%). There is no substantial difference in the average renal survival times between different geographical regions, with the exception of a better prognosis for idiopathic MN in Japan. The presenting clinical factors that most strongly predict subsequent poor outcome are similar for the three types of glomerulonephritis and are rather nonspecific: (1) severe proteinuria, (2) impairment of renal function, and (3) arterial hypertension. As for the histological features, the most powerful predictor of subsequent progression in all three types of glomerulonephritis is tubulointerstitial damage, suggesting that a cell-mediated immune process believed to occur there may independently influence outcome in glomerular diseases. PMID- 1415197 TI - EDTA-dependent pseudothrombocytopenia. PMID- 1415199 TI - The uremic dyslipidemia: a cross-sectional and longitudinal study. AB - Patients on maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) exhibit numerous disturbances of serum lipids and apoproteins that may contribute to their high cardiovascular mortality. Cross-sectional studies have found that lipid levels are inversely related to time on dialysis. However, it is not known whether this association is the result of the attrition of hyperlipidemic patients or a decrease in lipid levels over time in all patients. Additionally, few studies have investigated the effect of dialysis modality on the lipoprotein disturbances of uremia adjusting for the confounding influences of demographics, or nutritional and endocrine status. To address these issues, we undertook a cross-sectional and longitudinal study of lipids, apoproteins, and atherogenic risk ratios in patients maintained on HD and CAPD. Patients were enrolled in annual cohorts from 1987 to 1990 and monitored until 1991. A total of 196 HD and 77 CAPD patients were studied. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apoprotein (apo) A-I, and apo B were measured on enrollment and remeasured annually in survivors through 1990. Using multivariate methods, we examined the relationship of the lipids, apoproteins, their respective ratios, and their changes over time, to a broad range of clinical factors and to mortality. Compared with HD patients, CAPD patients had significantly higher TC, apo A-I, and apo B, and a significantly lower apo A-I/apo B ratio. Serum albumin correlated directly with TC and apo B and inversely with apo A-I/apo B. For patients with normal serum albumin (> or = 3.5 g/dL [35 g/L]), CAPD patients had a significantly higher TC/HDL-C than HD patients; otherwise the ratios were similar for CAPD and HD. Independent influences on lipoprotein levels in HD and CAPD patients were also demonstrated for race, gender, and diabetes, but not for parathyroid hormone (PTH) levels. For both dialysis modalities, patients who died had significantly lower TC and apo B, and significantly higher apo A-I/apo B throughout their entire courses compared with survivors. In the subset of patients followed longitudinally for 2 or more years, apo B tended to decrease with time, but TC, HDL-C, and apo A-I were stable. The longitudinal changes in lipoproteins did not correlate with outcome or other factors. In conclusion, CAPD patients have more atherogenic lipoprotein profiles than HD patients. Improved visceral protein nutritional status, as defined by serum albumin level, is associated with hyperlipidemia and, especially vor CAPD, worsened atherogenic risk ratios.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1415201 TI - Renal hemodynamics in recent-onset type II diabetes. AB - Glomerular hyperfiltration is thought to play an important role in the genesis of diabetic nephropathy. While hyperfiltration is well documented in early type I diabetes, the evidence for hyperfiltration in type II diabetes is conflicting. We investigated 16 nonproteinuric patients with recently diagnosed type II diabetes. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as inulin clearance (CIN) and p-aminohippuric acid clearance (CPAH) using a constant infusion technique. Lean body mass was measured by densitometry (weighing under water). Renal hemodynamics were also measured in 31 healthy volunteers and six obese nondiabetic individuals. Median GFR in diabetics (133 mL/min/1.73 m2; range, 95 to 165) was significantly (P < 0.01) higher than in obese nondiabetic controls (median, 118; range, 95 to 139). Elevated GFR (ie, > 95th percentile of nonobese healthy controls) was found in 44% of patients. When GFR was factored for lean body mass, it was elevated in 50%. GFR did not correlate with fasting glucose, hemoglobin A1C (HbA1C), insulin-like growth factors, IGF-1 and IGF-2, or somatomedin-binding protein (SMBP). The findings document that hyperfiltration is common in recent-onset type II diabetics. PMID- 1415200 TI - A trial of the prostaglandin E1 analogue, enisoprost, to reverse chronic cyclosporine-associated renal dysfunction. AB - Cyclosporine (CYA) reduces the renal synthesis of prostaglandins of the E series (PGE). Analogue of PGE1 have been shown to mitigate the vasoconstriction and abnormal renal function of experimental acute CYA nephrotoxicity. We examined the hypothesis that the orally bioavailable PGE analogue enisoprost (EP) would improve renal function in renal transplant recipients chronically exposed to CYA. In a randomized double-blind study, 40 patients at two centers who were being monitored for 3 to 30 months after renal transplantation, were allocated to receive either EP 100 micrograms orally four times daily or placebo (P) for 2 weeks. CYA dosing was fixed at existing levels. There could be no evidence of concurrent acute renal injury, including that of acute rejection. Glomerular filtration rate (GFR) was measured by the clearance of radiolabeled DTPA, while effective renal plasma flow (ERPF) was measured as the clearance of p aminohippuric acid (PAH). The acute effects of EP were examined twice, by comparing immediate postdose to predose values for GFR and ERPF on day 1 and again on day 14. Chronic effects were examined by comparing baseline (predose) values only for GFR and ERPF between days 1 and 14 and by an examination of creatinine clearances (CCR) on days 0, 14, and 21. At enrollment, patients were well matched for renal function (CCR:EP 47 +/- 5 v P 49 +/- 4 mL/min/1.73 m2; P = NS). Baseline demographics were similar, although patients treated with EP were older (46 +/- 2 v 36 +/- 3 years, mean +/- SEM, P = 0.003). CYA doses and blood levels did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415202 TI - Evidence for activation of tubuloglomerular feedback following nephrectomy in human subjects. AB - The intrarenal regulation of glomerular filtration rate (GFR) following a reduction in renal mass was evaluated in six normal subjects, studied before and 4 to 6 weeks after undergoing unilateral nephrectomy, performed for the purpose of living-related transplantation. The role of the tubuloglomerular feedback (TGF) system in regulating the final GFR on both occasions was assessed by determining the increase in GFR over baseline levels following blockade of TGF by a single dose of bumetanide, care being taken to replace sodium and water losses. Before donor nephrectomy, baseline GFR was 115 +/- 7 mL/min, which increased by 9.5% +/- 2.5% to 126 +/- 9 mL/min following the removal of TGF. Four to six weeks following donor nephrectomy, the baseline GFR was 83 +/- 8 mL/min, confirming significant hyperfiltration in the remaining kidney. After administration of bumetanide, the GFR increased by 15.6% +/- 3.1% to 96 +/- 9 mL/min. This greater fractional increase (P < 0.025) indicates an increase in tonic TGF activity in the uninephrectomized state compared with that demonstrated before nephrectomy. The results suggest that the hyperfiltration response following unilateral nephrectomy is limited by an appropriately activated TGF system. This phenomenon may be of importance in the maintenance of Na and water homeostasis, as well as limiting the pathological consequences that may result from, or be exacerbated by, an excessively high filtration rate in the remaining nephrons. Thus, dietary or therapeutic maneuvers that impair the TGF response may be best avoided following a reduction in renal mass. PMID- 1415203 TI - Vancomycin elimination during high-flux hemodialysis: kinetic model and comparison of four membranes. AB - Vancomycin clearance was measured in five patients during dialysis with cuprophane (CU), polysulfone (PS), cellulose triacetate (CT), and polyacrylonitrile (PAN) dialyzers. Vancomycin was significantly cleared during routine high-flux (HF) hemodialysis (HD) with the latter three membranes, but not by CU. Postdialytic rebound of serum vancomycin concentrations was noted following HF dialysis, necessitating use of a two-compartment pharmacokinetic model. Measurement of serum vancomycin concentration immediately postdialysis significantly overestimates intradialytic removal, possibly resulting in inappropriate dose adjustment. Vancomycin infusion during HF HD results in significant drug removal during its administration to the patient, complicating the calculation of an adequate dose. PMID- 1415204 TI - Improved lipid profiles in patients undergoing high-flux hemodialysis. AB - Hyperlipidemia is one of many atherogenic risk factors encountered by patients undergoing chronic hemodialysis (HD). We have studied lipid profiles in these patients and have found less hypertriglyceridemia in those undergoing high-flux HD than those receiving traditional HD. Mean +/- SEM triglyceride level was 1.62 +/- 0.15 mmol/L (143.3 +/- 13.6 mg/dL) in high-flux dialysis patients, 2.39 +/- 0.27 mmol/L (211.6 +/- 24.1 mg/dL) in conventional dialysis patients, and 1.55 +/ 0.13 mmol/L (137.1 +/- 11.5 mg/dL) in normal age- and sex-matched controls. In addition, we found that in patients undergoing high-flux HD, females had higher high-density lipoprotein2 (HDL2) levels (0.62 +/- 0.03 mmol/L [23.8 +/- 1.3 mg/dL]) than males (0.33 +/- 0.04 mmol/L [12.9 +/- 1.7 mg/dL]) (P < 0.01). The mechanism(s) responsible for divergent lipid profiles in subsets of HD patients deserves further investigation. Whether reductions of hypertriglyceridemia and/or increases of HDL2 will diminish the incidence of cardiovascular disease in dialysis patients is unknown. PMID- 1415205 TI - Calcium mass transfer with dialysate containing 1.25 and 1.75 mmol/L calcium in peritoneal dialysis patients. AB - Studies with 1.75 mmol/L calcium dialysate have shown that patients gain calcium from dialysate. Thus, hypercalcemia, especially when calcium compounds are used for phosphate control, is a commonly seen complication. Dialysate with 1.25 mmol/L calcium has been available since 1989. Little is known about calcium mass transfer (CMT) with dialysate of this calcium concentration. CMT was measured in 20 stable adult peritoneal dialysis patients. Each CMT study consisted of a 2-L continuous ambulatory peritoneal dialysis (CAPD) exchange with a dwell time of 4 hours. CMT studies were performed using 1.25 and 1.75 mmol/L calcium dialysate with 1.5, 2.5, and 4.25 g/dL dextrose concentrations. CMT with 1.25 mmol/L calcium dialysate was compared to that with 1.75 mmol/L for each dextrose concentration. With a dextrose concentration of 1.5 g/dL, the mean CMT for 1.25 mmol/L calcium dialysate was -0.1 +/- 0.3 mmol versus 0.6 +/- 0.3 mmol for 1.75 mmol/L calcium dialysate (P < 0.0001). A dextrose concentration of 2.5 g/dL resulted in a mean CMT of -0.4 +/- 0.2 mmol for 1.25 mmol/L calcium versus 0.45 +/- 0.25 mmol for 1.75 mmol/L calcium (P < 0.0001). Using a dextrose concentration of 4.25 g/dL, the mean CMT was -0.7 +/- 0.25 mmol for 1.25 mmol/L calcium versus -0.05 +/- 0.35 mmol for 1.75 mmol/L calcium (P < 0.0001). Mean serum ionized calcium (SiCa) was between 1.15 and 1.20 mmol/L for all study groups. CMT inversely correlated with SiCa for each type of dialysate used. CMT was dependent on the concentrations of calcium and dextrose in the dialysate and the SiCa level at the time of the exchange.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415206 TI - Specific opsonic activity for staphylococci in peritoneal dialysis effluent during continuous ambulatory peritoneal dialysis. AB - In a prospective study of intraperitoneal opsonins in 30 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), the IgG concentration, the fibronectin concentration, the specific antistaphylococcal antibody level, and the opsonic activity against Staphylococcus epidermidis were measured in peritoneal dialysis effluent from the initiation of CAPD and monthly for 6 months. Significant correlation was found between the four assays, but the interindividual and intraindividual variations were considerable. No statistically significant correlation was observed between susceptibility of the patients to CAPD-related infectious peritonitis and any of the above-mentioned parameters of humoral defense. We conclude that at the present time it is not feasible to use these assays for the establishment of prognosis with regard to peritonitis in CAPD. PMID- 1415208 TI - Looking upon the water. Sojourns along the Costa da Morte. PMID- 1415207 TI - Survival differences among older dialysis patients in the southeast. AB - Older end-stage renal disease (ESRD) patients treated by chronic dialysis have higher mortality in the United States than in many other countries. While increasing age, white race, male sex, and/or diabetes are considered risk factors for survival, few studies of older dialysis patients have simultaneously considered multiple predictor variables and their interactions. Using information contained in the 1982 to 1986 ESRD Network 20 database for Georgia and South Carolina, we studied hospitalizations and survival of 1,354 blacks and 965 whites who were age 60 years or older when they began dialysis therapy. Survival time was modeled using the Cox life-table regression method. Older blacks' median age at dialysis initiation was 67.4, compared with 68.7 for older whites (P = 0.001). Blacks were more likely than whites (P < 0.001) to have hypertension-related or diabetes-related ESRD. White patients experienced approximately 25% more hospitalization when adjustment was made for patient-days at risk. Separate multivariate survival models were required for patients with diabetes-related versus non-diabetes-related ESRD. Among diabetics, mortality was higher among whites and among patients who were older when they began dialysis. Among patients with non-diabetes-related ESRD, mortality was higher among patients who were older when they began dialysis, but the age effect was much stronger for white males. Our hospitalization and mortality data support the view that unmeasured severity (or frailty) differences characterize white as compared with black dialysis patients. Among non-diabetes-related ESRD patients, the age effect on survival was more severe in white males than in blacks or in white females. The high mortality we observed among older dialysis patients in Georgia and South Carolina warrants further study; the data may in part reflect patients' lower socioeconomic status compared with age, race, and sex-matched controls. PMID- 1415209 TI - Acute tubular necrosis associated with Lowe's syndrome: possible role of rhabdomyolysis. AB - The oculo-cerebral-renal syndrome of Lowe is an X-linked recessive disorder characterized by severe mental retardation, congenital cataracts, renal tubular dysfunction, growth retardation, hypotonia, glaucoma, and rickets. Recently, it has been found that serum concentrations of the muscle enzymes are elevated, providing evidence that there is primary muscle involvement in this disorder. The renal functional abnormalities that occur have also been further delineated. Renal tubular dysfunction presents within the first year of life, followed by a serum creatinine level that increases with age. Renal failure generally occurs in the fourth decade of life. We report two patients with Lowe's syndrome who presented with new onset of acute renal failure (ARF). Workup of their ARF established the diagnosis of acute tubular necrosis with evidence of rhabdomyolysis in one case. These patients were treated aggressively with dialysis and had subsequent recovery of renal function to their baseline state. We suggest that patients with Lowe's syndrome who present with an acute change in their renal function should be treated early with vigorous hydration therapy. If dialysis is indicated, it should be initiated. Furthermore, these patients should be promptly evaluated for evidence of rhabdomyolysis with alkalinization of the urine if possible. PMID- 1415210 TI - Henoch-Schonlein vasculitis as a manifestation of IgA-associated disease in cirrhosis. AB - Cirrhosis has been associated with a variety of glomerular lesions that generally include deposits of IgA in the mesangium. However, loss of renal function secondary to IgA deposition in cirrhotics is infrequent. An unusual patient who developed rapidly progressive glomerulonephritis followed by leukocytoclastic vasculitis with IgA deposition on skin biopsy is presented. We postulate that this is an example of Henoch-Schonlein purpura occurring secondary to altered IgA processing in cirrhosis. PMID- 1415211 TI - Pregnancy in patients on chronic ambulatory peritoneal dialysis. AB - Both conception and successful completion of pregnancy are rare occurrences in female patients on chronic renal replacement therapy. Only a handful of successful pregnancies and deliveries have been reported in patients receiving hemodialysis (HD). Even less common are reports of successful pregnancy and delivery in patients receiving chronic ambulatory peritoneal dialysis (CAPD). Among the more common causes of fetal loss are abruptio placentae and other causes of spontaneous miscarriage. We report here three cases of pregnancy in patients on CAPD; two of these pregnancies progressed successfully to spontaneous delivery, while the third terminated during an episode of acute peritonitis. Furthermore, we have reviewed the literature concerning the outcome of pregnancy in the dialysis population on CAPD. PMID- 1415212 TI - A case of rapidly progressive glomerulonephritis associated with bucillamine treated rheumatoid arthritis. PMID- 1415213 TI - The pathogenesis of hyperacute xenograft rejection. AB - A critical shortage of donor organs has driven many in the transplantation community to consider the use of animals as organ donors for humans, that is, xenotransplantation. While successful xenotransplantation of primate kidneys was achieved 25 years ago, most now advocate use of nonprimates as donors because of the risk of disease transmission and ethical concerns attendant to the use of primates. The major hurdle to xenotransplantation of organs between phylogenetically disparate species is the hyperacute rejection reaction that invariably destroys organ xenografts placed in unmodified recipients. Here we review recent insights concerning the pathogenesis of hyperacute rejection reactions. We focus particular attention on the endothelial cell, which serves not only as the target of xenoreactive antibodies and complement, but also, as a consequence of endothelial cell activation, as an instrument of tissue injury. We discuss a phenomenon called "accommodation" in which an organ graft acquires resistance to humoral-mediated injury. PMID- 1415214 TI - Should patients with hepatitis C virus antibodies in chronic hemodialysis be isolated? PMID- 1415215 TI - Genotype-phenotype relationships in human red/green color-vision defects: molecular and psychophysical studies. AB - The relationship between the molecular structure of the X-linked red and green visual pigment genes and color-vision phenotype as ascertained by anomaloscopy was studied in 64 color-defective males. The great majority of red-green defects were associated with either the deletion of the green-pigment gene or the formation of 5' red-green hybrid genes or 5' green-red hybrid genes. A rapid PCR based method allowed detection of hybrid genes, including those undetectable by Southern blot analysis, as well as more precise localization of the fusion points in hybrid genes. Protan color-vision defects appeared always associated with 5' red-green hybrid genes. Carriers of single red-green hybrid genes with fusion in introns 1-4 were protanopes. However, carriers of hybrid genes with red-green fusions in introns 2, 3, or 4 in the presence of additional normal green genes manifested as either protanopes or protanomalous trichromats, with the majority being protanomalous. Deutan defects were associated with green-pigment gene deletions, with 5' green-red hybrid genes, or, rarely, with 5' green-red-green hybrid genes. Complete green-pigment gene deletions or green-red fusions in intron 1 were usually associated with deuteranopia, although we unexpectedly found three carriers of a single red-pigment gene without any green-pigment genes to be deuteranomalous trichromats. All but one of the other deuteranomalous subjects had green-red hybrid genes with intron 1, 2, 3, or 4 fusions, as well as several normal green-pigment genes. The one exception had a grossly normal gene array, presumably with a more subtle mutation. Amino acid differences in exon 5 largely determine whether a hybrid gene will be more redlike or more greenlike in phenotype. Various discrepancies as to severity (dichromacy or trichromacy) remain unexplained but may arise because of variability of expression, postreceptoral variation, or both. When phenotypic color-vision defects exist, the kind of defect (protan or deutan) can be predicted by molecular analysis. Red green hybrid genes are probably always associated with protan color-vision defects, while the presence of green-red hybrid genes may not always manifest phenotypically with color-vision defects. Four subjects who were found to have 5' green-red hybrid genes in addition to normal red- and green-pigment genes had normal color vision as determined by anomaloscopy. These were discovered among a group of 129 Caucasian males who had been recruited as volunteers for a vision study.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1415216 TI - Evidence for genetic heterogeneity in tuberous sclerosis: one locus on chromosome 9 and at least one locus elsewhere. AB - Linkage of tuberous sclerosis complex (TSC), an autosomal dominant disorder, to markers on chromosome 9 was reported first in 1987. This assignment was confirmed by an international collaborative study that suggested more than one locus may be responsible for the phenotype. We studied 14 multigenerational TSC families (13 previously unreported) with markers for nine loci in the linked region of chromosome 9q32-q34. Our results confirm the previous reports that the genetic locus in one-third to one-half of families maps to chromosome 9. Comparison of clinical findings in the chromosome 9-linked families with those in the chromosome 9-unlinked families reveals only a higher incidence of ungual fibromata in the chromosome 9-linked families. PMID- 1415217 TI - Fluorescent multiplex linkage analysis and carrier detection for Duchenne/Becker muscular dystrophy. AB - We have developed a fast and accurate PCR-based linkage and carrier detection protocol for families of Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) patients with or without detectable deletions of the dystrophin gene, using fluorescent PCR products analyzed on an automated sequencer. When a deletion is found in the affected male DMD/BMD patient by standard multiplex PCR, fluorescently labeled primers specific for the deleted and nondeleted exon(s) are used to amplify the DNA of at-risk female relatives by using multiplex PCR at low cycle number (20 cycles). The products are then quantitatively analyzed on an automatic sequencer to determine whether they are heterozygous for the deletion and thus are carriers. As a confirmation of the deletion data, and in cases in which a deletion is not found in the proband, fluorescent multiplex PCR linkage is done by using four previously described polymorphic dinucleotide sequences. The four (CA)n repeats are located throughout the dystrophin gene, making the analysis highly informative and accurate. We present the successful application of this protocol in families who proved refractory to more traditional analyses. PMID- 1415218 TI - Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population. AB - Significant linkage disequilibrium has been found between the Huntington disease (HD) gene and DNA markers located around D4S95 and D4S98. The linkage disequilibrium studies favor the proximal location of the HD gene, in contrast to the conflicting results of recombination analyses. We have analyzed 45 Dutch HD families with 19 DNA markers and have calculated the strength of linkage disequilibrium. Highly significant linkage disequilibrium has been detected with D4S95, consistent with the studies in other populations. In contrast with most other studies, however, the area of linkage disequilibrium extends from D4S10 proximally to D4S95, covering 1,100 kb. These results confirm that the HD gene most likely maps near D4S95. PMID- 1415219 TI - Evidence against an X-linked locus close to DXS7 determining visual loss susceptibility in British and Italian families with Leber hereditary optic neuropathy. AB - Leber hereditary optic neuropathy (LHON) is associated with mutations of mtDNA, but two features of LHON pedigrees are not explicable solely on the basis of mitochondrial inheritance. There is a large excess of affected males, and not all males at risk develop the disease. These observations could be explained by the existence of an X-linked visual loss susceptibility gene. This hypothesis was supported by linkage studies in Finland, placing the susceptibility locus at DXS7, with a maximum lod score of 2.48 at a recombination fraction of 0. Linkage studies in 1 Italian and 12 British families with LHON, analyzed either together or separately depending on the associated mtDNA mutation, have excluded the presence of such a locus from an interval of about 30 cM around DXS7 in these kindreds, with a total lod score of -26.51 at a recombination fraction of 0. PMID- 1415220 TI - The autosomal dominant familial exudative vitreoretinopathy locus maps on 11q and is closely linked to D11S533. AB - Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is a hereditary disorder characterized by the incomplete vascularization of the peripheral retina. The primary biochemical defect in adFEVR is unknown. The adFEVR locus has tentatively been assigned to 11q by linkage studies. We report the results of an extended multipoint linkage analysis of two families with adFEVR by using five markers (INT2, D11S533, D11S527, D11S35, and CD3D) from 11q13-q23. Pairwise linkage data obtained in the two families were rather similar and hence have not provided evidence for genetic heterogeneity. The highest complied two-point lod score (3.67, at a recombination fraction of .07) was obtained for the disease locus versus D11S533. Multipoint analyses showed that the adFEVR locus maps most likely, with a maximum location score of over 20, between D11S533/D11S527 and D11S35, at recombination rates of .147 and .104, respectively. Close linkage without recombination (maximum lod score 11.26) has been found between D11S533 and D11S527. PMID- 1415221 TI - Power of sib-pair and sib-trio linkage analysis with assortative mating and multiple disease loci. AB - Sib-pair linkage analysis has been proposed for identifying genes that predispose to common diseases. We have shown that the presence of assortative mating and multiple disease-susceptibility loci (genetic heterogeneity) can increase the required sample size for affected-affected sib pairs several fold over the sample size required under random mating. We propose a new test statistic based on sib trios composed of either one unaffected and two affected siblings or one affected and two unaffected siblings. The sample-size requirements under assortative mating and multiple disease loci for these sib-trio statistics are much smaller, under most conditions, than the corresponding sample sizes for sib pairs. Study designs based on data from sib trios with one or two affected members are recommended whenever assortative mating and genetic heterogeneity are suspected. PMID- 1415222 TI - A double mutation in exon 6 of the beta-hexosaminidase alpha subunit in a patient with the B1 variant of Tay-Sachs disease. AB - The B1 variant form of Tay-Sachs disease is enzymologically unique in that the causative mutation(s) appear to affect the active site in the alpha subunit of beta-hexosaminidase A without altering its ability to associate with the beta subunit. Most previously reported B1 variant mutations were found in exon 5 within codon 178. The coding sequence of the alpha subunit gene of a patient with the B1 variant form was examined with a combination of reverse transcription of mRNA to cDNA, PCR, and dideoxy sequencing. A double mutation in exon 6 has been identified: a G574----C transversion causing a val192----leu change and a G598--- A transition resulting in a val200----met alteration. The amplified cDNAs were otherwise normal throughout their sequence. The 574 and 598 alterations have been confirmed by amplification directly from genomic DNA from the patient and her mother. Transient-expression studies of the two exon 6 mutations (singly or together) in COS-1 cells show that the G574----C change is sufficient to cause the loss of enzyme activity. The biochemical phenotype of the 574 alteration in transfection studies is consistent with that expected for a B1 variant mutation. As such, this mutation differs from previously reported B1 variant mutations, all of which occur in exon 5. PMID- 1415223 TI - Gaucher disease: A G+1----A+1 IVS2 splice donor site mutation causing exon 2 skipping in the acid beta-glucosidase mRNA. AB - Gaucher disease is the most frequent lysosomal storage disease and the most prevalent Jewish genetic disease. About 30 identified missense mutations are causal to the defective activity of acid beta-glucosidase in this disease. cDNAs were characterized from a moderately affected 9-year-old Ashkenazi Jewish Gaucher disease type 1 patient whose 80-year-old, enzyme-deficient, 1226G (Asn370----Ser [N370S]) homozygous grandfather was nearly asymptomatic. Sequence analyses revealed four populations of cDNAs with either the 1226G mutation, an exact exon 2 (delta EX2) deletion, a deletion of exon 2 and the first 115 bp of exon 3 (delta EX2-3), or a completely normal sequence. About 50% of the cDNAs were the delta EX2, the delta EX2-3, and the normal cDNAs, in a ratio of 6:3:1. Specific amplification and characterization of exon 2 and 5' and 3' intronic flanking sequences from the structural gene demonstrated clones with either the normal sequence or with a G+1----A+1 transition at the exon 2/intron 2 boundary. This mutation destroyed the splice donor consensus site (U1 binding site) for mRNA processing. This transition also was present at the corresponding exon/intron boundary of the highly homologous pseudogene. This new mutation, termed "IVS2 G+1 ---A+1," is the first splicing mutation described in Gaucher disease and accounted for about 3.4% of the Gaucher disease alleles in the Ashkenazi Jewish population. The occurrence of this "pseudogene"-type mutation in the structural gene indicates the role of acid beta-glucosidase pseudogene and structural gene rearrangements in the pathogenesis of this disease. PMID- 1415224 TI - Identification of two different point mutations associated with the fluoride resistant phenotype for human butyrylcholinesterase. AB - The fluoride variant of human butyrylcholinesterase owes its name to the observation that it is resistant to inhibition by 0.050 mM sodium fluoride in the in vitro assay. Individuals who are heterozygous for the fluoride and atypical alleles experience about 30 min of apnea, rather than the usual 3-5 min, after receiving succinyldicholine. Earlier we reported that the atypical variant has a nucleotide substitution which changes Asp 70 to Gly. In the present work we have identified two different point mutations associated with the fluoride-resistant phenotype. Fluoride-1 has a nucleotide substitution which changes Thr 243 to Met (ACG to ATG). Fluoride-2 has a substitution which changes Gly 390 to Val (GGT to GTT). These results were obtained by DNA sequence analysis of the butyrylcholinesterase gene after amplification by PCR. The subjects for these analyses were 4 patients and 21 family members. PMID- 1415225 TI - Lipoprotein(a) in women twins: heritability and relationship to apolipoprotein(a) phenotypes. AB - Lp(a) is a unique lipoprotein consisting of an LDL-like particle and a characteristic protein, apo(a). Increased levels of Lp(a) constitute a risk factor for coronary heart disease. Variation in the size of the apo(a) protein is a phenotype controlled by the apo(a) gene on chromosome 6 and is related to Lp(a) plasma levels. Based on 169 MZ and 125 DZ adult female twin pairs, this study's purpose was to estimate the proportion of the variation in Lp(a) levels that is due to genetic influences and to determine the extent to which the apo(a) locus explains this heritability. Lp(a) levels were significantly more similar in MZ twins than in DZ twins: mean co-twin differences were 3.9 +/- 5.7 mg/dl and 16.0 +/- 19.9 mg/dl (P less than .001), respectively. Intraclass correlations were .94 in MZ twins and .32 in DZ twins, resulting in a heritability estimate of .94 (P less than .001). Heritability was then calculated using only co-twins with the same apo(a) phenotype: the heritability estimate decreased to .45 but was still highly significant (P less than .001). Therefore, on the basis of heritability analysis of women twins, Lp(a) levels are almost entirely genetically controlled. Variation at the apo(a) locus contributes to this heritability, although other genetic factors could be involved. PMID- 1415226 TI - Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I. AB - von Willebrand disease (vWD) is the most common inherited bleeding disorder in humans. The disease is caused by qualitative and quantitative abnormalities of the von Willebrand factor (vWF). Genomic DNA from 25 patients with vWD type III, the most severe form of the disease, was studied using PCR followed by restriction-enzyme analysis and direct sequencing of the products. Nonsense mutations (CGA----TGA) were detected in exons 28, 32, and 45 by screening of all the 11 CGA arginine codons of the vWF gene. Two patients were found to be homozygous and five heterozygous for the mutation. Both parents and some of the relatives of the homozygous patients carry the mutation. These are the first reported examples of homozygous point mutations associated with the severe form of vWD. In the three heterozygous probands, one of the parents carried the mutation and had vWD type I. Family studies including parents and family members with or without vWD type I indicated that these three heterozygous patients are likely to be compound heterozygous. Twenty-one individuals from these seven families with vWD type I were found to be heterozygous for the mutation. PMID- 1415227 TI - Inter- and intrafamilial heterogeneity: effective sampling strategies and comparison of analysis methods. AB - Heterogeneity, both inter- and intrafamilial, represents a serious problem in linkage studies of common complex diseases. In this study we simulated different scenarios with families who phenotypically have identical diseases but who genotypically have two different forms of the disease (both forms genetic). We examined the proportion of families displaying intrafamilial heterogeneity, as a function of mode of inheritance, gene frequency, penetrance, and sampling strategies. Furthermore, we compared two different ways of analyzing linkage in these data sets: a two-locus (2L) analysis versus a one-locus (SL) analysis combined with an admixture test. Data were simulated with tight linkage between one disease locus and a marker locus; the other disease locus was not linked to a marker. Our findings are as follows: (1) In contrast to what has been proposed elsewhere to minimize heterogeneity, sampling only "high-density" pedigrees will increase the proportion of families with intrafamilial heterogeneity, especially when the two forms are relatively close in frequency. (2) When one form is dominant and one is recessive, this sampling strategy will greatly decrease the proportions of families with a recessive form and may therefore make it more difficult to detect linkage to the recessive form. (3) An SL analysis combined with an admixture test achieves about the same lod scores and estimate of the recombination fraction as does a 2L analysis. Also, a 2L analysis of a sample of families with intrafamilial heterogeneity does not perform significantly better than an SL analysis. (4) Bilineal pedigrees have little effect on the mean maximum lod score and mean maximum recombination fraction, and therefore there is little danger that including these families will lead to a false exclusion of linkage. PMID- 1415228 TI - The tyrosinase-positive oculocutaneous albinism locus maps to chromosome 15q11.2 q12. AB - Tyrosinase-positive oculocutaneous albinism (ty-pos OCA), an autosomal recessive disorder of the melanin biosynthetic pathway, is the most common type of albinism occurring worldwide. In southern African Bantu-speaking negroids it has an overall prevalence of about 1/3,900. Since the basic biochemical defect is unknown, a linkage study with candidate loci, candidate chromosomal regions, and random loci was undertaken. The ty-pos OCA locus was found to be linked to two arbitrary loci, D15S10 and D15S13, in the Prader-Willi/Angelman chromosomal region on chromosome 15q11.2-q12. The pink-eyed dilute locus, p, on mouse chromosome 7, maps close to a region of homology on human chromosome 15q, and we postulate that the ty-pos OCA and p loci are homologous. PMID- 1415230 TI - On the relationship between academic and private genetic services. PMID- 1415229 TI - J.B.S. Haldane (1892-1964): centennial appreciation of a polymath. PMID- 1415231 TI - Survival of academic-based genetic laboratory services. PMID- 1415232 TI - Descent into demonology and protectionism. PMID- 1415233 TI - Genetic discrimination and the Americans with Disabilities Act. PMID- 1415234 TI - Genetic distinctions are not necessarily examples of genetic discrimination. PMID- 1415235 TI - Muddling genetic discrimination. PMID- 1415237 TI - Perils of gene mapping with microsatellite markers. PMID- 1415236 TI - Genetic discrimination and insurance underwriting. PMID- 1415238 TI - Abuse of genetics in Nazi Germany. PMID- 1415239 TI - Minimum qualifications for directors: DNA-based genetic-testing laboratories. DNA Testing Subcommittee, Quality Assurance Committee, Council of Regional Networks for Genetic Services. PMID- 1415240 TI - Geneticists' responsibility to other health care professionals and to the lay public. PMID- 1415242 TI - A problem-based learning approach to teaching medical genetics. AB - A newly developed problem-based medical genetics course that was integrated into the fourth-year medical school curriculum of the University of Texas Health Science Center at San Antonio is described. To provide a basic genetic background for the clinical rotations, a supplemental computer tutorial is required during the second year. These two formats prepare the medical students to recognize genetic diseases, to provide basic genetic counseling in their daily practice, and to appropriately refer patients to genetic specialists. PMID- 1415241 TI - Genethics: project accountability via evaluation of teacher and student growth. AB - Accountability through demonstrated learning is increasingly being demanded by agencies funding science education projects. For example, the National Science Foundation requires evidence of the educational impact of programs designed to increase the scientific understanding and competencies of teachers and their students. The purpose of this paper is to share our human genetics educational experiences and accountability model with colleagues interested in serving the genetics educational needs of in-service secondary school science teachers and their students. Our accountability model is facilitated through (1) identifying the educational needs of the population of teachers to be served, (2) articulating goals and measurable objectives to meet these needs, and (3) then designing and implementing pretest/posttest questions to measure whether the objectives have been achieved. Comparison of entry and exit levels of performance on a 50-item test showed that teacher-participants learned a statistically significant amount of genetics content in our NSF-funded workshops. Teachers, in turn, administered a 25-item pretest/posttest to their secondary school students, and collective data from 121 classrooms across the United States revealed statistically significant increases in student knowledge of genetics content. Methods describing our attempts to evaluate teachers' use of pedagogical techniques and bioethical decision-making skills are briefly addressed. PMID- 1415243 TI - Twice-told tales: stories about genetic disorders. PMID- 1415244 TI - A candid look at Down syndrome. PMID- 1415245 TI - Dinucleotide repeat polymorphisms at the SCN4A locus suggest allelic heterogeneity of hyperkalemic periodic paralysis and paramyotonia congenita. PMID- 1415246 TI - The American Society of Human Genetics 42nd annual meeting. San Francisco, California, November 9-13, 1993. Abstracts. PMID- 1415247 TI - American Board of Medical Genetics restructuring: make an informed decision. PMID- 1415248 TI - DNA polymorphism analysis in families with recurrence of free trisomy 21. AB - We used DNA polymorphic markers on the long arm of human chromosome 21 in order to determine the parental and meiotic origin of the extra chromosome 21 in families with recurrent free trisomy 21. A total of 22 families were studied, 13 in which the individuals with trisomy 21 were siblings (category 1), four families in which the individuals with trisomy 21 were second-degree relatives (category 2), and five families in which the individuals with trisomy 21 were third-degree relatives, that is, their parents were siblings (category 3). In five category 1 families, parental mosaicism was detected, while in the remaining eight families, the origin of nondisjunction was maternal. In two of the four families of category 2 the nondisjunctions originated in individuals who were related. In only one of five category 3 families, the nondisjunctions originated in related individuals. These results suggest that parental mosaicism is an important etiologic factor in recurrent free trisomy 21 (5 of 22 families) and that chance alone can explain the recurrent trisomy 21 in many of the remaining families (14 of 22 families). However, in a small number of families (3 of 22), a familial predisposing factor or undetected mosaicism cannot be excluded. PMID- 1415249 TI - Localization of the photoreceptor gene ROM1 to human chromosome 11 and mouse chromosome 19: sublocalization to human 11q13 between PGA and PYGM. AB - Rom-1 is a retinal integral membrane protein that, together with the product of the human retinal degeneration slow gene (RDS), defines a photoreceptor-specific protein family. The gene for rom-1 (HGM symbol: ROM1) has been assigned to human chromosome 11 and mouse chromosome 19 by Southern blot analysis of somatic cell hybrid DNAs. ROM1 was regionally sublocalized to human 11p13-11q13 by using three mouse-human somatic cell hybrids; in situ hybridization refined the sublocalization to human 11q13. Analysis of somatic cell hybrids suggested that the most likely localization of ROM1 is in the approximately 2-cM interval between human PGA (human pepsinogen A) and PYGM (muscle glycogen phosphorylase). ROM1 appears to be a new member of a conserved syntenic group whose members include such genes as CD5, CD20, and OSBP (oxysterol-binding protein), on human chromosome 11 and mouse chromosome 19. Localization of the ROM1 gene will permit the examination of its linkage to hereditary retinopathies in man and mouse. PMID- 1415250 TI - Genetic determination of high-density lipoprotein-cholesterol and apolipoprotein A-1 plasma levels in a family study of cardiac catheterization patients. AB - Plasma levels of two lipoprotein risk factors, high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (apo A-1), have been shown to be negatively associated with the risk of developing coronary artery disease, and several reports have examined familial factors in HDL-C and apo A-1 levels. A number of studies suggest that shared genes influence familial resemblance of these lipoprotein levels far more than do shared environments. Possible mechanisms for the inheritance of these two risk factors (HDL-C and apo A-1 plasma levels) are explored using data from 390 individuals in 69 families ascertained through probands undergoing diagnostic cardiac catheterization. Segregation analysis was used to test a series of specific models of inheritance. Evidence for single-locus control of apo A-1 levels, with Mendelian transmission of a dominant allele leading to elevated apo A-1 levels, was seen in these families, although there was additional correlation among sibs present. This locus accounted for 48.6% and 37.2% of the total variation in apo A-1 levels in males and females, respectively. Similar evidence of segregation at a single locus controlling HDL-C levels was not seen in these families. PMID- 1415251 TI - Structure and chromosomal localization of the human antidiuretic hormone receptor gene. AB - Applying a genomic DNA-expression approach, we cloned the gene and cDNA coding for the human anti-diuretic hormone receptor, also called "vasopressin V2 receptor" (V2R). The nucleotide sequence of both cloned DNAs provided the information to elucidate the structure of the isolated transcriptional unit. The structure of this gene is unusual in that it is the first G protein-coupled receptor gene that contains two very small intervening sequences, the second of which separates the region encoding the seventh transmembrane region from the rest of the open reading frame. The sequence information was used to synthesize appropriate oligonucleotides to be used as primers in the PCR. The V2R gene was localized by PCR using DNA from hybrid cells as template. The gene was found to reside in the q28-qter portion of the human X chromosome, a region identified as the locus for congenital nephrogenic diabetes insipidus. PMID- 1415252 TI - Testing Hardy-Weinberg equilibrium on allelic data from VNTR loci. AB - Several methods for testing independence of pairs of alleles in a population that are obtained from a VNTR locus are presented. We assume an exchangeable quasi continuous distribution of the fragment lengths used to measure the allelic pairs. Bivariate-estimated quantiles computed from the quantiles of the entire data set are then utilized for testing independence. These methods have the advantage of being minimally susceptible to the criticism of (a) the inability of a technology to measure a few small-sized or rather large-sized fragments and (b) inadequate estimation of the homozygotic proportion. PMID- 1415253 TI - A Monte Carlo method for combined segregation and linkage analysis. AB - We introduce a Monte Carlo approach to combined segregation and linkage analysis of a quantitative trait observed in an extended pedigree. In conjunction with the Monte Carlo method of likelihood-ratio evaluation proposed by Thompson and Guo, the method provides for estimation and hypothesis testing. The greatest attraction of this approach is its ability to handle complex genetic models and large pedigrees. Two examples illustrate the practicality of the method. One is of simulated data on a large pedigree; the other is a reanalysis of published data previously analyzed by other methods. PMID- 1415254 TI - Cytochrome b558-negative, autosomal recessive chronic granulomatous disease: two new mutations in the cytochrome b558 light chain of the NADPH oxidase (p22-phox). AB - Chronic granulomatous disease (CGD) is characterized by the failure of activated phagocytes to generate superoxide. Defects in at least four different genes lead to CGD. Patients with the X-linked form of CGD have mutations in the gene for the beta-subunit of cytochrome b558 (gp91-phox). Patients with a rare autosomal recessive form of CGD have mutations in the gene for the alpha-subunit of this cytochrome (p22-phox). Usually, this leads to the absence of cytochrome b558 in the phagocytes (A22(0) CGD). We studied the molecular defect in five European patients from three unrelated families with this type of CGD. P22-phox mRNA was reverse-transcribed, and the coding region was amplified by PCR in one fragment and sequenced. Three patients from one family, with parents that were first cousins, were homozygous for a single base substitution (G-297-->A) resulting in a nonconservative amino acid change (Arg-90-->Gln). This mutation was previously found in a compound heterozygote A22(0) CGD patient. Another patient, also from first-cousin parents, was homozygous for an A-309-->G mutation in the open reading frame that predicts a nonconservative amino acid replacement (His-94- >Arg). The fifth patient was also born from a first-cousin marriage and was shown to be homozygous for the absence of exon 4 from the cDNA. In this patient, a G- >A substitution was found at position 1 of intron 4 in the genomic DNA. Therefore, the absence of exon 4 in the cDNA of this patient is due to a splicing error.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415255 TI - X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: localization to Xq12-q21.31 by X inactivation and linkage analysis. AB - We have examined seven pedigrees that include individuals with a recently described X-linked form of severe mental retardation associated with alpha thalassemia (ATR-X syndrome). Using hematologic and molecular approaches, we have shown that intellectually normal female carriers of this syndrome may be identified by the presence of rare cells containing HbH inclusions in their peripheral blood and by an extremely skewed pattern of X inactivation seen in cells from a variety of tissues. Linkage analysis has localized the ATR-X locus to an interval of approximately 11 cM between the loci DXS106 and DXYS1X (Xq12 q21.31), with a peak LOD score of 5.4 (recombination fraction of 0) at DXS72. These findings provide the basis for genetic counseling, assessment of carrier risk, and prenatal diagnosis of the ATR-X syndrome. Furthermore, they represent an important step in developing strategies to understand how the mutant ATR-X allele causes mental handicap, dysmorphism, and down-regulation of the alpha globin genes. PMID- 1415257 TI - A cooperative binomial ascertainment model. AB - It has been shown that the classical binomial form of ascertainment, assuming a constant probability pi that any affected individual may become a proband for his pedigree, cannot describe a rather wide range of ascertainment procedures that might arise in practice. Some more general heuristic ascertainment formulas might then be preferred, and in this paper we consider the probabilistic basis for these formulas. We retain the binomial assumption of the classical scheme but allow the ascertainment probability to depend on the number of potential probands per pedigree. This probability can be expressed by an increasing or a decreasing function of that number. Various illustrations are given and situations where the "cooperative" binomial scheme should be valuable are discussed. PMID- 1415256 TI - Different mosaicism frequencies for proximal and distal Duchenne muscular dystrophy (DMD) mutations indicate difference in etiology and recurrence risk. AB - In about 65% of the cases of Duchenne muscular dystrophy (DMD) a partial gene deletion or duplication in the dystrophin gene can be detected. These mutations are clustered at two hot spots: 30% at the hot spot in the proximal part of the gene and about 70% at a more distal hot spot. Unexpectedly we observed a higher frequency of proximal gene rearrangements among proved "germ line" mosaic cases. Of the 24 mosaic cases we are aware of, 19 (79%) have a proximal mutation, while only 5 (21%) have a distal mutation. This finding indicates that the mutations at the two hot spots in the dystrophin gene differ in origin. Independent support for the different mosaicism frequency was found by comparing the mutation spectra observed in isolated cases of DMD and familial cases of DMD. In a large two center study of 473 patients from Brazil and the Netherlands, we detected a significant difference in the deletion distribution of isolated (proximal:distal ratio 1:3) and familial cases (ratio 1:1). We conclude from these data that proximal deletions most likely occur early in embryonic development, causing them to have a higher chance of becoming familial, while distal deletions occur later and have a higher chance of causing only isolated cases. Finally, our findings have important consequences for the calculation of recurrence-risk estimates according to the site of the deletion: a "proximal" new mutant has an increased recurrence risk of approximately 30%, and a "distal" new mutant has a decreased recurrence risk of approximately 4%. PMID- 1415258 TI - National Institutes of Health Workshop Statement. Reproductive genetic testing: impact on women. PMID- 1415259 TI - The forensic DNA brouhaha: science or debate? PMID- 1415260 TI - The ceiling principle is not always conservative in assigning genotype frequencies for forensic DNA testing. PMID- 1415261 TI - Conflicts, ethics, and the genome. PMID- 1415263 TI - The need for care in the use of linkage analysis for genetic diagnosis in small families, with particular reference to uniparental disomy. PMID- 1415262 TI - DNA banking. PMID- 1415264 TI - A prospective cytogenetic study of 36 cases of DiGeorge syndrome. AB - Cytogenetic analysis was carried out in a prospective series of 36 children with DiGeorge syndrome. High-resolution banding (> 850 bands/haploid set) was achieved in 30 cases. Monosomy 22q11.21-->q11.23 was found in 9 of these 30 cases. In each of these cases monosomy 22q11.21-->q11.23 resulted from an interstitial deletion and not from a translocation. No other chromosome abnormalities were seen. PMID- 1415265 TI - Molecular genetic study of the frequency of monosomy 22q11 in DiGeorge syndrome. AB - It is well established that DiGeorge syndrome (DGS) may be associated with monosomy of 22q11-pter. More recently, DNA probes have been used to detect hemizygosity for this region in patients with no visible karyotypic abnormality. However, DGS has also been described in cases where the cytogenetic abnormality does not involve 22q11; for instance, four cases of 10p- have been reported. In this study we have prospectively analyzed patients, by using DNA markers from 22q11, to assess the frequency of 22q11 rearrangements in DGS. Twenty-one of 22 cases had demonstrable hemizygosity for 22q11. Cytogenetic analysis had identified interstitial deletion in 6 of 16 cases tested; in 6 other cases no karyotype was available. When these results are combined with those from our previous studies, 33 of 35 DGS patients had chromosome 22q11 deletions detectable by DNA probes. PMID- 1415266 TI - Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis. AB - The Y chromosome gene SRY (sex-determining region, Y gene) has been equated with the mammalian testis-determining factor. The SRY gene of five subjects with 46,XY complete gonadal dysgenesis (46,XY karyotype, completely female external genitalia, normal Mullerian ducts, and streak gonads) was evaluated for possible mutations in the coding region by using both single-strand conformation polymorphism (SSCP) assay and DNA sequencing. Mutations were identified in three subjects, of which two gave altered SSCP patterns. Two of them were point mutations causing amino acid substitutions, and the third was a single-base deletion causing a frameshift. All three mutations caused alterations in the putative DNA-binding region of the SRY protein. Genomic DNA was obtained from the fathers of two of the three mutant patients: one mutation was demonstrated to be de novo, and the other was inherited. The presence of SRY mutations in three of five patients suggests that the frequency of SRY mutations in XY females is higher than current estimates. PMID- 1415267 TI - A new source of polymorphic DNA markers for sperm typing: analysis of microsatellite repeats in single cells. AB - We show that dinucleotide and tetranucleotide repeat polymorphisms can be analyzed in single cells without using radioactivity or denaturing gels. This provides a rich new source of DNA polymorphisms for genetic mapping by sperm typing. The recombination fraction between two CA repeat polymorphisms was determined after whole genome amplification of single sperm, followed by typing of two different aliquots, one aliquot for each polymorphic locus. Single-cell analysis of microsatellites may also be valuable both for preimplantation genetic disease diagnosis based on single-blastomere or polar-body analysis and for the typing of forensic or ancient DNA samples containing very small amounts of nucleic acid. PMID- 1415268 TI - Independence of VNTR alleles defined as floating bins. AB - Data bases of VNTR fragments determined for Caucasians and blacks by Cellmark Diagnostics and Lifecodes Corporation are analyzed for independence of variants within and between loci. Floating bins are constructed around specific fragment lengths and are used to define discrete genotypes. Simple chi 2 test statistics for independence of bins within and between loci are described and applied to large sets of randomly generated four-locus profiles. The proportions of significant test statistics were about as expected under the hypotheses of independence, suggesting the absence of both Hardy-Weinberg and linkage disequilibrium. In any particular forensic application, however, these tests need to be performed on the fragments in question. PMID- 1415270 TI - Primary neoplasms of the pleura. A report of five cases. PMID- 1415269 TI - Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. AB - A large number of familial Alzheimer disease (FAD) kindreds were examined to determine whether mutations in the amyloid precursor protein (APP) gene could be responsible for the disease. Previous studies have identified three mutations at APP codon 717 which are pathogenic for Alzheimer disease (AD). Samples from affected subjects were examined for mutations in exons 16 and 17 of the APP gene. A combination of direct sequencing and single-strand conformational polymorphism analysis was used. Sporadic AD and normal controls were also examined by the same methods. Five sequence variants were identified. One variant at APP codon 693 resulted in a Glu-->Gly change. This is the same codon as the hereditary cerebral hemorrhage with amyloidosis-Dutch type Glu-->Gln mutation. Another single-base change at APP codon 708 did not alter the amino acid encoded at this site. Two point mutations and a 6-bp deletion were identified in the intronic sequences surrounding exon 17. None of the variants could be unambiguously determined to be responsible for FAD. The larger families were also analyzed by testing for linkage of FAD to a highly polymorphic short tandem repeat marker (D21S210) that is tightly linked to APP. Highly negative LOD scores were obtained for the family groups tested, and linkage was formally excluded beyond theta = .10 for the Volga German kindreds, theta = .20 for early-onset non-Volga Germans, and theta = .10 for late-onset families. LOD scores for linkage of FAD to markers centromeric to APP (D21S1/S11, D21S13, and D21S215) were also negative in the three family groups. These studies show that APP mutations account for AD in only a small fraction of FAD kindreds. PMID- 1415271 TI - Organic solvent encephalopathy: an old hazard revisited. AB - This report describes neurologic and respiratory symptoms among 26 engineers and contract laborers who used organic solvents and detergents to remove polychlorinated biphenyl contamination from a poorly ventilated factory basement. Neurologic symptoms included persistent central nervous system deficits; these developed in one worker after only 3 days. Respiratory symptoms included cough that persisted for more than 2 years. Laborers were more likely to report symptoms than were engineers. Appropriate ventilation or respirator use might have prevented the workers' morbidity. This incident serves as a reminder that organic solvent-related occupational illness continues to occur despite worker health regulations and knowledge of preventive measures. PMID- 1415272 TI - Further scientific issues in determining an occupational standard for cadmium. AB - This contribution responds to the recent paper of Thun et al. (American Journal of Industrial Medicine 20:629-642, 1991) on an occupational standard for cadmium. The contribution of non-invasive in situ measurements of cadmium in liver and in kidney to the study of cadmium industrial toxicology is particularly reviewed. It is contended that clear scientific grounds do not exist for recommending cadmium in air occupational standard below 10 micrograms m-3, and that other arguments would need to be adduced to support a recommendation for a lower level. Last, a number of unanswered questions are identified and the need for further work is highlighted. PMID- 1415273 TI - Health physics: its development, successes, failures, and eccentricities. AB - Health Physics began at the University of Chicago as a science and profession during the early World War II years. It was initiated by Drs. A.H. Compton and R.S. Stone, director and associate director, respectively, of the early Plutonium Project cryptically called the Metallurgical Laboratory. It was to be a science and a profession to protect radiation workers and members of the public from exposure to ionizing radiation. It succeeded to some extent in this objective but during the past decade in the United States, it has reverted into an organization primarily to protect the nuclear industry from liability resulting from radiation exposure. PMID- 1415274 TI - Social class and mortality in occupational cohorts. PMID- 1415275 TI - Re: "Social class and mortality in occupational cohorts". PMID- 1415276 TI - Social class and mortality in occupational cohorts. PMID- 1415277 TI - Query on non-back occupational injuries. PMID- 1415278 TI - Disease clusters in occupational medicine: a protocol for their investigation in the workplace. AB - Disease clusters have been an important source of epidemiologic and medical information in the history of occupational medicine. Many accepted disease exposure linkages were first observed and investigated as disease clusters in the workplace setting. Recent interest in disease cluster methodology has focused on traditional environmental settings. There has been very little work on a similar methodology for the investigation of disease clusters in the workplace, despite the many advantages of workplace cluster investigations for recognizing new etiologic associations. In this paper, a protocol is proposed and discussed which can be implemented in both acute and chronic disease cluster outbreaks in the workplace, where no obvious previously recognized cause is identified. A standardized approach to occupational disease cluster investigation will lead to increased efficiency, decreased social-political tensions, and a greater yield of scientific information. PMID- 1415279 TI - Lung function and exposure to asbestos among vehicle mechanics. AB - Vehicle mechanics (n = 99) exposed to asbestos (annual median value 0.08 f/ml), and local controls (n = 83) not occupationally exposed to asbestos were studied with regard to symptoms and pulmonary function. The inclusion criteria to participate in this study was an age of at least 40 years with no known exposure to lung irritating agents, and for the exposed subjects, more than 15 years occupational exposure to asbestos with at least 20 years from the first exposure. The subjects were studied during identical conditions by means of dynamic and static spirometry, single breath wash-out with nitrogen (N2) and carbon monoxide (CO). The median for cumulative exposure of asbestos during the entire work life among the studied mechanics was 2.3 f*y/ml. The mechanics had reduced transfer factor (TLCO), after adjustment for age, height, and smoking category. A significant dose-response relationship was noted between the cumulative exposure of asbestos and CV%. The findings suggest a slight influence of small airways and alveoli. The evaluation of the prognostic significance of this requires a longitudinal study. PMID- 1415280 TI - General mortality and respiratory cancer among a cohort of male chemical workers in California. AB - Cohort mortality and nested case-control studies were conducted involving 2,901 men employed 1 year or more between 1940 and 1986 at any of four California facilities of a major chemical company. Employees experienced fewer deaths from each of the major causes than were expected based on U.S., California, and local county mortality rates. Respiratory cancer was significantly elevated in one socioeconomic category comprised of operators (SMR = 157, 95% CI = 109-220). The 34 cases who died from respiratory cancer and 136 matched controls, all of whom were operators, were included in a nested case-control study. Departments in which subjects had worked were grouped into 13 work assignment or product categories by an industrial hygienist without knowledge of case-control status. Smoking habits and other occupational exposures were ascertained by telephone interview from subjects or surrogate-responders. As expected, current cigarette smoking was strongly related to respiratory cancer. After adjustment for smoking, cases were significantly more likely than controls to have ever worked in one of the 13 work areas (supervision, services, and business support). However, no dose response relationship was evident with duration of employment in this work area and the departments involved were associated with plant security and not chemical production. Results were similar when a 15-year latency period was assumed. These findings suggest that the excess of respiratory cancer mortality among operators was most likely due to differences in cigarette smoking or other factors not ascertained, rather than to a specific occupational exposure. PMID- 1415281 TI - Assessment of exposure to carbon disulfide in viscose production workers from urinary 2-thiothiazolidine-4-carboxylic acid determinations. AB - The follow-up of environmental carbon disulfide (CS2) exposure and urinary excretion of 2-thiothiazolidine-4-carboxylic acid (TTCA) among 20 operatives over a 4-day working week in two viscose producing factories confirmed earlier observations that TTCA is a sensitive and reliable indicator of exposure to CS2. Exposure to as low as 0.5-1.0 ppm (1.6-3.2 mg/m3) of CS2 (8-hour time-weighted average [TWA]) was associated with detectable amounts of TTCA in end-of-shift urine. Moreover, the excretion of TTCA, relative to estimated CS2 uptake, appeared surprisingly constant in the studied work force. Approximately 3% (range 2-6.5%) of absorbed CS2 was detected in urine as TTCA. The proportional TTCA excretion did not show dose dependency in the estimated CS2 dose range which varied by about 20-fold. TTCA elimination exhibited both a fast (T 1/2 6 hour) and a slow (T 1/2 68 hour) phase. The slow elimination is compatible with a high lipid solubility and reversible protein binding of CS2. Consequently, urinary excretion of TTCA, relative to CS2 exposure, increased by about a third during the workweek. Urinary TTCA concentration of 4.5 mmol/mol creatinine in a postshift sample corresponded to a TWA exposure to 10 ppm CS2 towards the end of the working week. PMID- 1415282 TI - Hormone status in occupational toluene exposure. AB - Twenty toluene-exposed rotogravure printers, without signs of solvent-induced toxic encephalopathy, had lower median plasma levels of follicle stimulating hormone (FSH) (3.2 vs. 4.9 IU/L; p = .02) and luteinizing hormone (LH) (6.4 vs. 7.2 IU/L; p = .05) and also lower serum levels of free testosterone (7.8 vs. 86.8 pmol/L; p = .05), respectively, than 44 unexposed referents. The individual time weighted toluene levels in air were 36 (median; range 8-111) ppm. The printers' median toluene levels in blood were 1.7 (1.0-6.6) mumol/l, and in subcutaneous adipose tissue 5.7 (2.5-21) mg/kg fat. There was a negative association between blood toluene and plasma levels of prolactin. In eight printers, the levels of FSH and LH increased during a 4 week vacation, while the levels of thyroid stimulating hormone, free triiodothyronine, and free thyroxine decreased during the same period. The results indicate a slight, reversible effect of toluene on the cortical level or on the hypothalamic-pituitary axis at exposures well below the permissible levels, possibly mediated through an effect on catecholamine neurotransmission. PMID- 1415283 TI - Reevaluation of silicosis and lung cancer in North Carolina dusty trades workers. AB - We previously reported on the lung cancer mortality through 1983 of 760 males who were diagnosed with silicosis during 1930-1983 by the State of North Carolina's medical examination program for dusty trades workers. The lung cancer SMR (95% confidence interval) was 2.6 (1.8-3.6) among 655 white members of this group. In this paper, we report the results of a reanalysis of mortality among a subgroup for whom chest radiographs were currently available for rereading. Technically acceptable radiographs were available for 306 white males and were independently reclassified for pneumoconiosis by 3 "B" readers using the 1980 ILO Classification. Lung cancer SMRs were 1.7 (0.8-3.1) for the entire group of 306 white males, 2.5 (1.1-4.9) for 143 subjects reclassified as simple silicosis, and 1.0 (0.1-3.5) for 96 subjects whose radiographs were reclassified as ILO category 0. There were no lung cancer deaths among 67 subjects whose radiographs were reclassified as progressive massive fibrosis. Corresponding lung cancer SMRs for subjects who had never been employed in a job with exposure to known occupational carcinogens were 1.2 (0.2-4.4) for those reclassified as category 0, and 2.4 (1.0 5.0) for those reclassified as having simple silicosis. The age-adjusted lung cancer rate ratio among subjects with simple silicosis compared to those with category 0 was 1.5 (0.4-5.8). Our findings from this reanalysis, which effectively controls for misclassification of silicosis due to errors in radiograph interpretation by North Carolina program readers, offer additional evidence consistent with the hypothesis of an association between silicosis and lung cancer in this study group. PMID- 1415284 TI - Respiratory disorders and atopy in cotton, wool, and other textile mill workers in Denmark. AB - A cross-sectional study of respiratory disorders and atopy in Danish textile industry workers was conducted to survey respiratory symptoms throughout the textile industry, to estimate the association of these disorders with atopy, and to study dose-response relationships within the cotton industry. Workers at cotton mills, a wool mill, and a man-made fiber (MMF) mill were examined. Four hundred nine (90%) of the 445 workers participated in this survey, i.e., 253, 62, and 94 workers at the cotton mills, the wool mill, and the MMF mill, respectively. An interview designed to assess the prevalence of common respiratory and allergic symptoms was given to all workers willing to participate, and blood samples were drawn. Lung function measurements determined a baseline FEV1, FVC and the change in FEV1 and FVC during work hours on a Monday. The working environment was examined for dust, bacteria, endotoxins, and molds, and the exposure was estimated for each participant. The mean personal samples of airborne respirable dust and respirable endotoxin were highest in the cotton industry, i.e., 0.17-0.50 mg/m3 and 9.0-126 ng/m3 respectively, whereas mold spores were found in the highest concentrations in the wool mill: 280-791 colony-forming units (cfu)/m3. Only small concentrations of microorganisms were found in the MMF mill. The mean change in FEV1% and FVC% was greatest among atopic individuals in both cotton and wool industry and other textile industries although the differences were not significant. FEV1% and FVC% in the cotton workers were significantly associated with the cumulative exposure to respirable endotoxin. Byssinosis was diagnosed only in the cotton industry. We found a dose response relationship between endotoxin exposure and byssinosis, and a significant association between A-1-A serum concentrations less than or equal to 35 mumol/liter and byssinosis, a finding we are further evaluating in subsequent studies. PMID- 1415285 TI - Localized pleural plaques and lung cancer. AB - In a mass chest radiography survey conducted in 1971 for 7,986 residents of three Finnish communities, 604 subjects (7.6%) with pleural plaques but not other asbestos-related radiographic signs were identified. The same number of referents, each individually matched to each plaque carrier on sex, birth year, and community, was selected from among persons in the same source population with no pleural plaques. The two groups were followed for investigation of incidence of lung cancer during 1972-1989. Twenty-eight of those with plaques and 25 referents contracted lung cancer (crude conditional RR = 1.1; CL95 = 0.7, 1.9). The application of the proportional hazards model, with adjustment for sex, age, and residence, resulted in a hazard ratio of 1.1 (CL = 0.6, 1.8). The risk ratio estimate may be biased; hence, the result is inconclusive in regard to the predictive assessment of lung cancer risk among carriers of pleural plaques. PMID- 1415286 TI - Asbestos fiber analysis in 27 malignant mesothelioma cases. AB - The asbestos body counts per 5 gm wet lung tissue in 27 (23 pleural and 4 peritoneal) malignant mesothelioma cases derived from 19 autopsy and 8 surgical cases were, according to our own criteria, low level exposure in 13 cases (48.2%), moderate level exposure in 2 cases (7.4%), and high level exposure in 12 cases (44.4%). In our previous study on 235 consecutive autopsy cases, the low level exposure was considered to be environmental, the moderate level was secondary or blue collar, and the high level was occupational. In the present study, about half of the cases examined (44.4%, high level exposure) are closely related to some occupational asbestos exposure and the other half (48.2%) to environmental exposure. The type and size of asbestos fibers from the 12 cases of high level exposure were analyzed and the characteristics were compared with those of cases of low level exposure without lung cancer or mesothelioma. Most fibers analyzed (98%) were longer than 5 microns and thicker than 0.10 micron by our counting rules. In the control group, predominant fibers were tremolite or actinolite. In all the 11 pleural mesothelioma cases, the content of amosite fibers was significantly higher than in the controls. In one case of peritoneal mesothelioma, incipient asbestosis was found and the predominant fibers were crocidolite. It is suggested that the presence of amosite and crocidolite is linked to mesothelioma. The mean lengths of amosite and crocidolite, as detected by our resolution capabilities, were 36.0 and 20.9 microns, and the mean diameters were 0.51 and 0.27 micron, respectively. Both amosite and crocidolite fibers had high aspect ratios (94.2 and 115.4). PMID- 1415287 TI - A retrospective mortality study within operating segments of a petroleum company. AB - This retrospective mortality study was conducted among 34,597 oil industry workers in diverse operating segments. Employees were traced through Statistics Canada, and overall mortality (SMR = 0.85) was lower than general population rates and similar to other petrochemical cohorts. The most notable finding was a significant excess of malignant melanoma [observed deaths (N) = 16, SMR = 1.87, 95% CI = 1.07, 3.04], which concentrated among upstream workers (N = 6, SMR = 6.00, 95% CI = 2.19, 13.06), and was directly related to employment duration and latency. Specific substances or hydrocarbon (HC) streams could not be implicated, although possible explanations include dermal HC exposure, ultraviolet light exposure, or a synergistic effect between these two factors. Marketing/transportation workers showed a non-significant excess of multiple myeloma (SMR = 1.81), which was also related to employment duration, latency, and commencement of employment before 1950. Lymphatic cancer, skin cancer, and kidney cancer mortality was not elevated in refinery workers, a finding at odds with some previous refinery worker studies. Although the malignant melanoma and possibly the multiple myeloma mortality patterns are consistent with an occupational link, further studies are needed to investigate the relationship of these diseases with particular exposures. PMID- 1415288 TI - An automated method for the determination of acetyl and pseudo cholinesterase in hemolyzed whole blood. AB - The aim of the present study was to develop a method which allows determination of pseudo (PsChE) and acetyl cholinesterase (AChE) activities in single hemolyzed blood samples of workers exposed to cholinesterase-inhibiting compounds, avoiding the time-consuming and laborious separation of plasma and erythrocytes. Two methods based on Ellman's colorimetric determination of cholinesterase activity were compared, and three different substrates were tested. The best results were obtained with the substrates butyrylthiocholine and acetyl(beta methyl)thiocholine, both showing a substrate specificity of more than 97% with respect to PsChE and AChE, respectively. The method showed sensitivity to detect low levels of inhibition of AChE and PsChE in blood. The between-day precision was less than 4% for both cholinesterase activities. It was demonstrated with this method that hemolyzed blood can be stored at -20 degrees C at least 18 months without loss of cholinesterase activity. The method has been used for 18 months in a monitoring program for laboratory employees working with various cholinesterase-inhibiting compounds. The average co-efficients of intraindividual variation amounted to 6.8% (range 2.2-9.6%; 90 percentile, 8%) and 6.6% (range 2.9-9.9%; 90 percentile, 7.9%) for PsChE and AChE, respectively. In a group of non-exposed workers the average intraindividual variations were 4.0% (range 1.5 7.7%; 90 percentile, 7.6%) and 3.6% (range 0.6-6.6%; 90 percentile, 5.3%), respectively. Using the value of 4.0%, it appears possible to detect an individual decrease in cholinesterase activity of more than 8% below a baseline based on three determinations. The method can thus be used to detect relatively low levels of cholinesterase inhibition. PMID- 1415289 TI - Biological monitoring of three 60Co radiation incident victims. AB - Radiation-induced structural chromosomal aberrations were the only adverse effects found in three workers overexposed to 60Co gamma-radiation. Chromosomal analyses were performed on the 5th and 75th days after exposure. Hematologic follow-up was carried out on the 5th, 12th, 16th, and 75th days after exposure. Hematologic findings did not differ over time in any of the three exposed workers. In two workers, we found dicentric chromosomes, which are conventional indicators for exposure to ionizing radiation. PMID- 1415290 TI - Medical management of three workers following a radiation exposure incident. AB - The medical management of three individuals involved in an exposure incident to whole-body radiation at a nuclear generating plant of a Canadian electrical utility is described. The exposure incident resulted in the two highest whole body radiation doses ever received in a single event by workers in a Canadian nuclear power plant. The individual whole-body doses (127.4 mSv, 92.0 mSv, 22.4 mSv) were below the threshold for acute radiation sickness but the exposures still presented medical management problems related to assessment and counseling. Serial blood counting and lymphocyte cytogenetic analysis to corroborate the physical dosimetry were performed. All three employees experienced somatic symptoms due to stress and one employee developed post-traumatic stress disorder. This incident indicates that there is a need in such radiation exposure accidents for early and continued counseling of exposed employees to minimize the risk of development of stress-related symptoms. PMID- 1415291 TI - Fifty-year experience in diagnosing asbestos-related cancers in Finland: progress and detours. PMID- 1415292 TI - Re: "Attitudes and opinions: asbestos and cancer". PMID- 1415293 TI - Re: "Attitudes and opinions regarding asbestos and cancer 1934-1965". PMID- 1415294 TI - Re: "Changing attitudes and opinions regarding asbestos and cancer 1934-1965". PMID- 1415295 TI - Re: "Attitudes and opinions regarding asbestos and cancer 1934-1965". PMID- 1415296 TI - Re: "Changing attitudes and opinions regarding asbestos and cancer 1934-1965". PMID- 1415297 TI - Comments on "Evidence of biased recording of radiation doses of Hanford workers". PMID- 1415298 TI - Thyroid cancer in thyroid nodules: finding a needle in the haystack. PMID- 1415299 TI - Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity. AB - PURPOSE: We evaluated the frequency of thyroid cancer in patients with cold thyroid nodules in relation to iodine intake, sex, age, and multinodularity in a consecutive series of patients with nodular thyroid diseases. PATIENTS: In the period from 1980 to 1990, 5,637 patients were studied: 4,176 patients were from an iodine-sufficient area (ISA) and 1,461 from an adjacent iodine-deficient area (IDA). Surgery was performed in 792 patients on the basis of a suspicious or malignant finding at fine-needle aspiration biopsy. RESULTS: The overall thyroid cancer frequency was 4.6% (259 patients had cancer). Iodine intake affected the cancer rate in patients with cold nodules. The frequency of cancer in patients with cold thyroid nodules was 5.3% in the ISA and 2.7% in the IDA. This difference, however, was significant only in females. Sex had a major influence on the malignant rate of cold nodules; although female patients were more frequently observed (n = 5,028) than male patients (n = 609), the frequency of cancer was significantly lower in female patients with cold nodules (4.2%) than in males (8.2%). Age was an important factor in both sexes. The proportion of nodules that were malignant was smallest in patients of the 4th decade and was greatest in patients younger than 30 years or older than 60 years. Multivariate analysis showed that sex and age interact in determining the cancer risk in patients with thyroid nodules. Finally, the frequency of thyroid cancer in patients with a solitary nodule was not different from the frequency in patients with multiple nodules. CONCLUSION: Our study indicates that thyroid cancer risk in a patient with a nodular goiter varies markedly according to iodine intake, sex, and age but not in relation to multinodularity, as assessed by clinical examination. The knowledge of these epidemiologic aspects of thyroid cancer may increase the accuracy of the preoperative selection of patients with cold nodules of the thyroid. PMID- 1415300 TI - Human immunodeficiency virus infection in intravenous drug users: a model for primary care. AB - PURPOSE: Intravenous drug users (IVDUs) often encounter barriers to primary care. To improve access, we developed a primary care clinic--Central Medical Unit (CMU) -for substance abusers in drug treatment. We report outcomes for services offered to IVDUs with human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS: During 1990, 24% (120 of 509) of IVDUs eligible for CMU were HIV positive. Diagnostic therapeutic and preventive goals for IVDUs with HIV infection were evaluated for acceptance and compliance by chart review for these 120 patients. RESULTS: On admission, 65% (78 of 120) of patients reported having no source of primary care, 64% (77 of 120) were male, and 77% (92 of 120) were in methadone maintenance. All were screened for tuberculosis, syphilis, and hepatitis; 94% (15 of 16) of eligible patients accepted tuberculosis prophylaxis and 83% (5 of 6) accepted syphilis treatment, but only 36% (5 of 14) accepted hepatitis B vaccine. Of those who accepted therapy, 87% (13 of 15) were compliant with tuberculosis prophylaxis, and 100% (5 of 5) were compliant with syphilis treatment. Influenza vaccine was accepted by 49% (59 of 120) and pneumococcal vaccine by 81% (97 of 120). Ninety-eight percent (118 of 120) accepted T-cell testing: 61% had T-helper counts less than 500/mm3 and 25% were less than 200/mm3. Of those eligible, 89% (70 of 79) accepted antiretroviral therapy, and 100% (35 of 35) accepted Pneumocystis carinii pneumonia prophylaxis. Six-month compliance rates for these therapies were 84% (59 of 70) and 77% (27 of 35), respectively. CONCLUSION: By offering primary care services with drug treatment, the CMU model may be an effective way of providing access to primary care for HIV-infected IVDUs and for facilitating compliance. PMID- 1415301 TI - Causes of death in persons with human immunodeficiency virus infection. AB - PURPOSE: Pneumocystis carinii pneumonia (PCP) was reported to be the predominant cause of human immunodeficiency virus (HIV)-related deaths prior to 1988, the year that effective prophylaxis against PCP entered routine use. Our study was performed to study the causes of HIV-related death since January 1988 in a region where patient tracking is virtually complete. PATIENTS AND METHODS: We surveyed physicians associated with the Brown University Acquired Immunodeficiency Syndrome (AIDS) Program who cared for greater than 95% of known HIV-positive patients in Rhode Island. These physicians identified all those HIV-infected persons who had died under their care between January 1988 and July 1990, and determined these patients' causes of death by chart review. For comparison, death certificates of identified persons were also reviewed at the Rhode Island Department of Vital Statistics. RESULTS: Among 126 deaths since January 1988, bacterial infections were the most common cause of death (30%), whereas PCP was responsible for only 16% of deaths. Persons not receiving any form of PCP prophylaxis were more likely to die from PCP than were those who received prophylaxis (26% versus 11% [p = 0.04]). Cause of death as recorded on actual death certificates was imprecise, although bacterial infections were again the most common cause indicated. Only one death occurred in a patient with a CD4 count greater than 200/mL, and this was not HIV-related. CONCLUSION: PCP has not been the leading cause of death in our region since January 1988. Bacterial infections contribute substantially to mortality, and this may influence future prophylactic regimens. HIV-related deaths in patients with CD4 counts greater than 200/mL are unusual. PMID- 1415302 TI - Idiopathic intracranial hypertension: report of seven cases. AB - We describe seven patients with idiopathic intracranial hypertension (IIH), a disorder, mostly in young women, characterized by papilledema, elevated cerebrospinal fluid (CSF) pressure, normal CSF composition, and normal neuroradiologic studies. Obesity, the most consistent etiologic association, was present in two of our patients. Hypothalamic compression in IIH may induce increased appetite and result in weight gain. Use of trimethoprim/sulfamethoxazole has been reported to be associated with IIH and was seen in one of our patients. IIH is an important diagnostic consideration in the differential diagnosis for a patient with headache, visual disturbances, and papilledema. PMID- 1415303 TI - Interaction of cyclosporine A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis. AB - PURPOSE: To determine the additive renal effects of nonsteroidal anti inflammatory drugs (NSAIDs) and cyclosporine A (CYA) in patients with rheumatoid arthritis (RA) and to determine the effects of CYA on active RA. PATIENTS AND METHODS: Eleven patients with RA refractory to other agents were treated separately for 2-week periods with an NSAID (sulindac or naproxen), CYA (5 mg/kg/d), and NSAID plus CYA in combination (NSAID/CYA). The NSAID/CYA combination was continued for an additional 20 weeks. Clinical parameters of RA, electrolytes, renal function, and the renin-aldosterone system were evaluated at each interval to determine the potential interaction of these two agents. RESULTS: Combined therapy was effective in suppressing many measures of active RA in 9 of the 11 patients. Adverse drug reactions were common, but withdrawals were limited to hirsutism (one) and peripheral neuropathy (one). In about half of the patients, CYA or NSAID resulted in a decrease in the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), with a mild reduction in the filtration fraction. With NSAID or CYA, early morning renin-aldosterone system values were mildly suppressed, and their response to ambulation/intravenous (IV) furosemide was not blunted. When combined, NSAID/CYA caused more marked reductions of GFR and ERPF at 2 weeks, and this persisted at 20 weeks. The morning renin-aldosterone system values during administration of NSAID/CYA were suppressed, with an added blunted response to ambulation/IV furosemide. CONCLUSION: As previously suspected, the impairment of renal function when CYA and NSAID are combined is greater than that obtained with either agent alone. This hemodynamic effect was reversible and appeared to be, at least in part, due to renal vasoconstriction. PMID- 1415304 TI - Prevention of anticardiolipin antibody-related pregnancy losses with prednisone and aspirin. AB - PURPOSE: Prevention and treatment of pregnancy loss associated with the antiphospholipid syndrome (APS) are controversial. Successful pregnancies have been reported with prednisone and low-dose aspirin in patients with lupus anticoagulant and anticardiolipin antibodies (aCL), but failure has also been reported. The purpose of this prospective study was to define the efficacy of such combination therapy in the prevention of pregnancy loss related to aCL. PATIENTS AND METHODS: Consecutive pregnant patients with a minimum of one pregnancy loss and at least two positive aCL determinations more than 3 months apart, and in whom other causes of pregnancy loss were ruled out, were included in the study. aCL concentrations were determined by enzyme-linked immunosorbent assay before and during therapy. Patients received prednisone, at a dosage of 40 mg/d, for 4 weeks. The dose was then tapered down 10 mg every 4 weeks, and then to a maintenance dose of 5 mg/d. They also received aspirin, 81 mg/d, throughout the pregnancy. Babies were evaluated during the pregnancy by measurement of fetal heart rate and ultrasonography, and after the delivery by measurement of weight and Apgar scores, and, in some cases, by arterial gasometry. RESULTS: Eleven patients with a mean (+/- SD) age of 33.2 +/- 5.01 years were included. Prior to therapy, the rate of live-born babies was 15.6% (32 previous fetal losses and 5 live-born babies), and, after therapy, it was 100% (12 pregnancies and 12 live born babies). There were no significant adverse effects to either mothers or babies. All the patients had positive aCL determinations. Nine patients had positive IgG aCL. The levels of the antibodies decreased during treatment in these nine patients. IgM aCL determinations were positive in nine patients. The levels of this isotype decreased in eight patients (90%) during treatment. CONCLUSIONS: Treatment with prednisone and aspirin appears to be efficacious, safe, and economic in the prevention of pregnancy loss and fetal growth retardation in patients with aCL. PMID- 1415305 TI - Implementation of capillary blood glucose monitoring in a teaching hospital and determination of program requirements to maintain quality testing. AB - PURPOSE: To study the implementation of bedside capillary glucose monitoring using a hospital-wide quality control (QC) program. METHODS: A prospective study of QC performance in 7 outpatient and 39 inpatient treatment units was performed in a large teaching hospital over a 2-year period. Approximately 800 nurses were trained to perform bedside capillary glucose monitoring (Accu-Chek II, Boehringer Mannheim, Indianapolis, IN). An eight-point QC program was instituted including proficiency testing, instrument maintenance, performance of daily controls, storage of reagent strips and supplies, instrument calibration, and documentation procedures. RESULTS: Comparison of laboratory and bedside test results (split sample proficiency testing) revealed Y = 1.004X + 7.26, r = 0.95, with a mean percent difference of -4.2% (p < 0.001). Less than 7% of results fell outside +/- 20% of the laboratory results. QC scores (0 = worst to 4 = best), based on adherence to the QC program, improved from 0 on the first inspection to 3.7 +/- 0.17 by the 11th inspection. The most common QC deficiencies were failure to perform split-sample testing (41.4%) and failure to perform instrument maintenance (30.2%). Significant differences were noted in the QC performance of different types of medical services. During the 2-year study period, the total number of glucose assays performed in the clinical laboratories decreased by 22.2% concurrent with initiation of bedside testing. The number of instruments in the hospital increased from 10 to 46. CONCLUSIONS: Bedside capillary glucose assays can be widely implemented in large hospitals with an acceptable degree of accuracy. QC programs with frequent inspections are necessary to identify units that function inadequately, and a formal disciplinary policy is required to ensure compliance with the program. PMID- 1415306 TI - Epidemiologic features and clinical presentation of acute Q fever in hospitalized patients: 323 French cases. AB - PURPOSE: To contribute to the knowledge of epidemiologic and clinical features of patients hospitalized with Q fever in France. METHODS: We conducted a retrospective analysis of 22,496 sera submitted between 1982 and 1990 to the French National Reference Center for Rickettsial Diseases (NRC). The diagnosis of acute Q fever was based on an IgG titer greater than or equal to 1:200 and an IgM titer greater than or equal to 1:25 against phase II Coxiella burnetii antigen on an indirect immunofluorescence test (IFA). Fifteen cases prior to 1985 were diagnosed on the basis of a complement fixation titer greater than or equal to 1:8. A serosurvey of blood donors from Marseille was also conducted in 1988 on 924 sera, using IFA with a cutoff titer of 1:25. RESULTS: The serosurvey conducted in 1988 showed a seroprevalence of 4.03%, without age or sex prediction. The incidence rate of acute Q fever detection at the NRC was 0.58 per 100,000 inhabitants over the 9-year period. Three hundred twenty-three clinical cases were diagnosed, rising from 1 in 1982 to 107 in 1990. In patients hospitalized for acute Q fever, there was a significantly higher sex ratio of males to females (2.3), which, coupled with the age distribution, indicated that elder males, who are overrepresented due to our recruitment bias, are more susceptible to C. burnetii infections. The mean age of the patients was 45.5 years, while the risk was increased in the 30 to 39 age group as well as in the 60 to 69 age group. Usual epidemiologic risk factors were found in 20.1% of the cases. Hepatitis (61.9%) was a more common clinical presentation in our patients with Q fever than pneumonia (45.8%). This might reflect differences in strains of C. burnetii or the biology of the host. However, French farmers and stock breeders commonly drink unpasteurized raw milk from their cattle, which might indicate a relationship between hepatitis and infection via the digestive tract. CONCLUSION: Our results indicate that many cases of acute Q fever are undiagnosed. A greater awareness of the disease and more extensive serologic testing of patients with symptoms compatible with Q fever may improve the situation. PMID- 1415307 TI - Splenectomy in advanced chronic lymphocytic leukemia: a single institution experience with 50 patients. AB - PURPOSE: To assess the efficacy of splenectomy in the treatment of refractory cytopenias associated with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: The histories of 57 patients with CLL who underwent splenectomy at the Mayo Clinic between 1975 and 1991 were retrospectively reviewed. Of the 57 patients, 50 underwent splenectomy for reasons directly related to their disease process such as cytopenias or symptomatic splenomegaly. The histories from these 50 patients were studied to assess the response to splenectomy and the operative morbidity and mortality. RESULTS: Ninety-four percent of patients were in Rai stage III or IV with extensive marrow infiltration, massive splenomegaly, and cytopenias refractory to chemotherapy. A positive response to splenectomy was defined at 3 months of follow-up as: (1) a hemoglobin level of 11 g/dL or greater in a patient with a preoperative value less than 11 g/dL; or (2) a platelet count of 100 x 10(3)/mm3 or greater in a patient with a preoperative value less than 100 x 10(3)/mm3. A positive response was achieved in 77% of patients with anemia, 70% of patients with thrombocytopenia, and 64% of patients with both anemia and thrombocytopenia. The response was sustained at 1 year of follow-up in 86%, 84%, and 85% of the patients, respectively. Postoperative transfusion requirements decreased correspondingly. The operative morbidity was 26%, and the operative mortality was 4%. The mean duration of hospitalization was 9.8 days (median: 9 days; range: 5 to 24 days). The actuarial median survival after splenectomy was 41 months in responders and 14 months in nonresponders. We found no preoperative parameters that were clearly predictive of a poor hematologic response. In particular, outcome was not affected by preoperative spleen size or the degree of marrow infiltration by CLL. All patients with symptomatic splenomegaly had an improved sense of well-being. CONCLUSION: In this, the largest single institution study to date, we found splenectomy to be efficacious in providing durable remissions of refractory cytopenias and in relieving symptomatic splenomegaly in the majority of patients with CLL. The procedure is associated with a low perioperative mortality. Although the impact on survival is uncertain, the improved peripheral blood counts may allow the administration of adequate doses of myelosuppressive chemotherapy. PMID- 1415308 TI - Lessons from my father. PMID- 1415309 TI - Multiple myeloma and chronic lymphocytic leukemia: parallels and contrasts. AB - Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) are closely related B-cell cancers. Parallel and divergent features of these diseases are reviewed. In MM, expression of multiple hemopoietic lineage-associated antigens on the malignant cells and the substantial likelihood of progression to acute myelogenous leukemia suggest transformation of a pluripotent stem cell. In CLL, transformation more likely involves a committed B-cell progenitor. Another difference is that clonal evolution with associated cytogenetic progression is common in MM but not CLL. Other data, including studies of proto-oncogenes and tumor suppressor genes, suggest that MM results both from increased proliferation and accumulation of tumor cells, whereas tumor cell accumulation is the predominant feature of CLL. These differences may be reflected in the seemingly greater role of cytokine abnormalities in MM progression. For example, osteoclast activating properties of some cytokines account for bone involvement in MM but not in CLL. MM and CLL share common features such as stage-dependent anemia and immune deficiency. Both diseases respond to alkylating agents but vary markedly in their sensitivity to fludarabine (CLL greater than MM) and glucocorticoids (MM greater than CLL). Differences between these diseases in progression-free interval and survival may reflect different definitions of premalignant and malignant phases rather than biologic differences. Detailed comparisons between MM and CLL may provide additional insights into these and related B-cell cancers. PMID- 1415310 TI - T-cell receptor alpha/beta chain-CD3 protein complex defect in systemic lupus erythematosus: T-cell function. AB - We describe the first case of systemic lupus erythematosus (SLE) in which peripheral blood T cells were deficient in cell surface expression of T-cell receptor alpha/beta chain (TcR alpha beta) and the CD3 protein. Because of the uncommon phenotype and because of the notion that coexpression of TcR alpha beta and CD3 is essential for antigen-specific T-cell function, in vitro functional assays were performed, showing a highly decreased proliferative response to anti CD3 antibody and other T-cell mitogens, deficient interleukin-2 (IL-2) secretion, and impaired function to respond in autologous and allogeneic mixed lymphocyte reactions. However, the helper-inducer function of T cells was unaffected by deficient expression of the TcR alpha beta/CD3 protein complex. The relative increase of CD4+ CDw29+ helper-inducer subsets in T cells accounted for elevated secretion of two terminal B-cell stimulating factors, B-cell growth factor (BCGF) and B-cell differentiation factor (BCDF). Hence, our results suggest that the regulation of secretion of lymphokines, IL-2, and BCGF and BCDF is independently controlled in T cells, and this case illustrates the pathologic sequelae of a unique defect in T cells characteristic of SLE. PMID- 1415311 TI - Skin necrosis and protein C deficiency associated with vitamin K depletion in a patient with renal failure. AB - Skin necrosis similar to that induced by warfarin was seen in a patient who had never received the drug but who was vitamin K-deficient due to malnutrition and prolonged treatment with broad-spectrum antibiotics. He also had end-stage renal failure and was receiving prophylactic subcutaneous heparin therapy because of immobilization. His plasma protein C antigen level and, disproportionately, his plasma protein C functional activity were decreased. Both protein C values improved after vitamin K therapy, discontinuation of heparin, and initiation of hemodialysis. We surmise that skin necrosis occurred as a result of protein C deficiency caused by vitamin K depletion. Production of abnormal (descarboxy) protein C/protein S due to vitamin K deficiency and increased protein C inhibitory activity associated with renal failure and/or heparin administration may have contributed to the clinical picture. This rare but serious complication of a relatively common disorder, viz., vitamin K deficiency, reinforces the importance of vitamin K supplementation in malnourished patients who receive long term antibiotic maintenance therapy. PMID- 1415312 TI - Asymmetric clubbing as a manifestation of sarcoid bone disease. PMID- 1415313 TI - Disseminated Mycobacterium fortuitum disease in an AIDS patient. PMID- 1415314 TI - Use of antimalarial drugs for the treatment of psoriatic arthritis. PMID- 1415315 TI - Efficacy of barium enemas in the elderly. PMID- 1415316 TI - Low-dose interferon-alpha for mixed cryoglobulinemia associated with hepatitis C virus. PMID- 1415317 TI - Relationship between insulin sensitivity and degree of obesity in mild hypertension. AB - Eighteen patients with mild hypertension (diastolic blood pressure > or = 90 and < 104 mm Hg) and 15 normotensive control subjects were studied. Insulin tolerance tests (ITT) and fasting plasma insulin (FPI) level measurements were performed to evaluate insulin sensitivity. Insulin sensitivity, as measured with the ITT, showed a strong correlation with body mass index (BMI) in the hypertensive and control groups (r = -0.68, p < 0.01 and r = -0.61, p < 0.01, respectively). The fasting insulin levels also correlated significantly with BMI in both groups (r = 0.55, p < 0.05 in the hypertensive and r = 0.76, p < 0.01 in the control group). Insulin sensitivity in the hypertensive subjects whose BMI was < or = 27.0 kg/m2 (nonobese), as measured with the ITT and FPI, was not different from the nonobese normal controls (K(itt), 5.36 +/- 1.74% min-1 versus 5.61 +/- 1.66% min-1, respectively, p > 0.2; FPI, 5.8 +/- 3.4 microU/ml versus 7.1 +/- 2.5 microU/ml, respectively, p > 0.2). Also, insulin sensitivity, as measured with the ITT, was not statistically significantly different between hypertensive and normotensive obese subjects (K(itt), 2.82 +/- 1.55% versus 3.90 +/- 0.67% min-1, respectively, p > 0.1). When fasting plasma insulin levels were compared, a higher level was observed in the obese normotensive subjects than in the obese hypertensive group (FPI, 19.8 +/- 10.0 microU/ml and 11.5 +/- 4.9 microU/ml, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415319 TI - Comparison of four methods for assessing airway bacteriology in intubated, mechanically ventilated patients. AB - A prospective evaluation of lower airway bacteriology from intubated, mechanically ventilated patients was performed by comparing the qualitative and quantitative recovery of bacteria using four different techniques. Twelve intubated, mechanically ventilated patients who satisfied accepted clinical criteria for the suspicion of ventilator-associated pneumonia were studied. Airway secretions were obtained from each patient by: (1) blind endotracheal aspiration (ET); (2) Accu-cath pulmonary culture catheter (Accu); (3) bronchoscopic protected specimen brush (BPSB); and (4) bronchoalveolar lavage (BAL). ET specimens were cultured semi-quantitatively (1+ to 4+) aerobically, and all other specimens were cultured quantitatively both aerobically and anaerobically. The BPSB recovered 9 organisms in > or = 10(3) colony forming units/ml, a standard number often used to indicate significant growth. Of these 9 organisms, 7 were recovered at > or = 10(3) cfu/ml by Accu, and 6 were recovered at > or = 10(4) cfu/ml by BAL. All 8 aerobic isolates recovered in > or = 10(3) cfu/ml by BPSB also were recovered by ET aspirate. Five of these were recovered in > or = 3+ semi-quantitative growth by ET aspirate. Of 30 organisms recovered in < 3+ semi-quantitative growth by ET aspirate, 28 were recovered in < 10(3) cfu/ml by BPSB, indicating a negative predictive value of 93%. Thus, it appears that these four methods provide reasonably similar qualitative and quantitative recovery of bacteria from the lower airways of intubated, mechanically ventilated patients. In addition, routine Gram's stain and semi-quantitative aerobic culture of endotracheal aspirate may provide useful information in patients with suspected ventilator-associated pneumonia. PMID- 1415318 TI - Cloning and expression of a human endothelin receptor: subtype A. AB - The polymerase chain reaction, employing degenerate primers specific for the intramembrane domains III and VI of G-coupled receptors, was used to generate partial clones encoding those receptors carried by cultured rat aorta smooth muscle cells. One clone, spanning the intramembrane domains IV-VI of a receptor specific for endothelin-1 (ET-R[A]), was used as a probe to screen a human placental cDNA library. The clone pL4-3, encoding a selective type of human endothelin receptor (ET-R[A]), has an open reading frame encoding a protein 427 amino acids in length, with a relative molecular weight of 48,625 daltons. The sequence analysis suggests the presence of a signal peptide, two potential sites for glycosylation in the N terminal extracellular domain, the seven transmembrane domains typical of G-protein receptors, and several potential sites for phosphorylation in the C terminal cytoplasmic domain. At the amino acid level, the human ET-R(A) shows 91% and 94% identity with the rat and bovine ET-R(A)s, respectively, and 59% similarity with the human ET-R(B). Xenopus laevis oocytes injected with the cloned cDNA express binding sites specific for endothelin-1. Expression of the message in COS 7 cells gave a membrane-bound product to which binding of the [125I]-ET-1 was inhibited by peptide analogues specific for ET R(A). PMID- 1415320 TI - Surfactant protein-A inhibits lavage-induced surfactant secretion in newborn rabbits. AB - In vitro experiments with granular pneumocytes suggest that surfactant protein-A (SP-A) inhibits secretion of pulmonary surfactant. We examined whether SP-A inhibits surfactant secretion induced by lung distention during lung lavage. Human SP-A was obtained by lung lavage in a patient with pulmonary alveolar proteinosis. After centrifugation of the lavagate, the pellet was repeatedly washed with saline and then extracted with chloroform:methanol. The methanol:saline phase was separated and lyophilized to yield the SP-A product. SDS-PAGE and immunoblot analysis indicated that our preparation of SP-A had only minor contamination with human plasma proteins. To examine secretion, we used freshly killed newborn rabbit pups of 29.5 days gestation and lavaged the lungs by 10 sequential, fresh saline washes. Littermate neighbor pairs were lavaged with SP-A or human plasma protein at concentrations of 1, 6, 10, and 50 micrograms/ml, and disaturated phosphatidylcholine (DSPC) was analyzed as a marker for surfactant. The inhibition of surfactant secretion was maximal at a concentration of 10 micrograms/ml; the average yield by the last two pairs of washes, an index of surfactant secretion, was 286 +/- 41 micrograms/g dry lung weight for SP-A, compared to 405 +/- 37 micrograms/g dry lung weight for controls, an inhibition of 30% (p < 0.005). There were no changes in the volumes of returned lavage or in the concentrations of lactate dehydrogenase or DNA. To test whether SP-A increased cellular uptake of DSPC in the lungs, we prepared radioactive exogenous surfactant, lavaged it into the lungs, and monitored recovery of radioactivity by continued lavage. Recovery was the same in treated and control lungs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415321 TI - Case report: lymphadenopathy, perinodal granulomatosis, and immunologic aberrations. AB - The authors report on a patient with an undescribed constellation of lymph nodal plasmacytosis, perinodal epithelioid cell granulomas and fibrosis as well as anti Sm and anti-phospholipid antibodies. The illness does not meet the criteria of well-known nosologic entities, but it is thought to represent an unrecognized nosological entity within the group of undifferentiated immune disorders. PMID- 1415322 TI - Case report: stimulation of severe hypertension as a means of malingering. AB - Severe hypertension frequently requires hospitalization. Although hospital admission is undesirable for most patients, others are motivated to achieve hospitalization status for secondary gain. The authors present a case of a prison inmate who simulated severe hypertension with a combination of Valsalva's maneuver and arm flexion, on the background of preexisting essential hypertension and mitral valve prolapse. His secondary intent--to avoid his prison duties- classifies him as a malingerer. The differences between this malingering and the psychiatric diagnosis of Munchausen syndrome are discussed. The contributions of essential hypertension and mitral valve prolapse to the self-induced blood pressure elevations also are considered. PMID- 1415323 TI - Loxoscelism. AB - Loxoscelism, or envenomation by the brown recluse spider, may result in necrotic lesions and systemic reactions, including hemolytic anemia. Histologically, it resembles a cutaneous Arthus reaction. The reaction mechanism involves interactions between complement, neutrophils, and the clotting system. It is best treated with analgesics, avoidance of early surgical debridement, and oral dapsone. PMID- 1415324 TI - The impact of World War II on U.S. medicine. PMID- 1415325 TI - Five years experience of predictive testing for myotonic dystrophy using linked DNA markers. AB - We report on a 5 year experience in providing presymptomatic and prenatal molecular diagnostic services for myotonic dystrophy, using closely linked markers, representing 235 completed results in 161 families. Only 10 analyses (4.3%) proved uninformative, but a further 5 requests (1.9%) could not be reported because of uncertainty in clinical status. Seven of 81 (8.6%) patients considered to be at low risk on clinical grounds were found to be at high risk of carrying the gene. The importance of interpreting molecular results in conjunction with clinical findings is emphasised by the illustrative examples provided. Careful clinical examination and appropriate investigation remain a cornerstone of diagnosis in myotonic dystrophy and are crucial if errors in assigning genotype status by molecular means are to be minimised. PMID- 1415327 TI - Can maternal risk factors influence the presence of major birth defects in infants with Down syndrome? AB - Although the manifestations of Down syndrome (DS) are well known, certain major birth defects such as duodenal atresia and endocardial cushion defects are present in some infants but not others, suggesting the possible role of other genetic or environmental factors interacting with the trisomy genotype. To explore the possible role of maternal factors in the presence of major defects among DS infants, we examined data from an epidemiologic study of DS conducted in metropolitan Atlanta. Of 219 DS infants born between 1968 and 1980, 50 had recorded cardiac defects, 9 had selected gastrointestinal atresias and 4 had oral clefts. We evaluated the association of these defects with several maternal factors including age, race, first trimester cigarette smoking, alcohol use, and fever. We found that different maternal factors were associated with several defects: (1) mother's race with cardiac defects (40% in blacks vs. 17% in whites, P less than 0.01), (2) mother's age with oral clefts (6% for less than 25 years, 1% for 25-34, and 0% for greater than 34, P less than 0.05), and (3) maternal first trimester fever with gastrointestinal defects (15% in infants with history of fever and 3% in infants without a history of fever, P less than 0.01). We also observed an inverse relationship between maternal alcohol use and the presence of ventricular septal defect. These findings suggest that maternal risk factors may influence the clinical manifestations of DS. In addition to searching for a genetic basis for the DS phenotype, we suggest that the role of environmental factors and maternal exposures be specifically explored in clarifying the genesis of various birth defects in Down syndrome. PMID- 1415326 TI - X inactivation and dystrophin studies in a t(X;12) female: evidence for biochemical normalization in Duchenne muscular dystrophy carriers. AB - A 4-year-old girl was identified with high creatine kinase (CK) values, and mild muscle weakness in a limb-girdle distribution. Results of dystrophin analysis of the muscle biopsy were consistent with a manifesting heterozygote for Duchenne muscular dystrophy. In peripheral lymphocytes she had a t(X;12) (p21.2;q24.33). Late DNA replication studies demonstrated inactivation of the normal X chromosome in 99.4% of cells. Dystrophin immunofluorescence showed 64% dystrophin-negative muscle fibers. Dystrophin content of muscle by immunoblot was approximately 5% of normal. The discordance between the percent of normal X inactivation and percent of dystrophin-negative cells may be explained by compensatory protection of dystrophin by rare nuclei with the normal X active in multi-nucleated muscle fibers with shared cytoplasm. PMID- 1415328 TI - Detection of the heteromorphic spectrum of heterochromatin in the human genome by in situ digestion using restriction endonuclease AluI. AB - A battery of selective banding techniques has been utilized to identify the heteromorphic markers in the human genome. The recent addition of the AluI/Giemsa (G)-technique has helped not only in identifying the variable sites, but in characterizing their heteromorphic spectra. In the present investigation, we classified the pericentromeric heterochromatin by the AluI/G-technique by its size and position using 50 normal individuals and suggested the potential uses of this banding technique over earlier methods. PMID- 1415329 TI - Microcephaly, lymphedema, and chorioretinal dysplasia: a distinct syndrome? AB - We report on 2 unrelated patients with microcephaly, lymphedema, and chorioretinal changes. They are compared with previously reported patients with microcephaly and lymphedema and microcephaly with chorioretinal changes. The question is raised whether all of these patients represent one entity or are separate syndromes. Until more data are available we propose that our patients represent a single entity. PMID- 1415330 TI - VACTERL with hydrocephalus: one end of the Fanconi anemia spectrum of anomalies? AB - Two cases of Fanconi anemia presenting as hydrocephalus are discussed. Both infants had initially been considered to have features of VACTERL. Chromosomal breakage studies should be performed in all cases of VACTERL with hydrocephalus so that Fanconi anemia may be excluded. PMID- 1415331 TI - VACTERL or MURCS association in a girl with neurenteric cyst and identical thoracic malformations in the father: a case of gonosomal mosaicism? AB - We report on a female infant with lethal congenital malformations including extreme hydrocephalus due to aqueductal stenosis, vertebral segmentation anomalies, fused costae, anal atresia, renal dysplasia, and bicornuate uterus with a double blind vagina. The VACTERL and the MURCS associations are possible diagnoses. Her father had a neurenteric cyst in infancy. He has identical vertebral and costal malformations as his daughter but is otherwise healthy. The possibility of dominant inheritance with gonosomal mosaicism in the father is discussed. PMID- 1415332 TI - Ring chromosome 7, hyperpigmented skin lesions and malignant melanoma. PMID- 1415333 TI - Metacarpophalangeal pattern profiles: Q-score for ages 3 years to adult with epiphyses: an update. PMID- 1415334 TI - Spinal muscular atrophy and probable Duchenne muscular dystrophy occurring separately in closely related Melanesian families in Papua, New Guinea. PMID- 1415335 TI - Fetal hypokinesia sequence caused by maternal autoimmune disorder? PMID- 1415336 TI - Applications of the concept of attributable fraction in medical genetics. PMID- 1415337 TI - Tightly linked polymorphic markers for fragile X syndrome and prenatal cytogenetic diagnostic experience. AB - Linkage analysis using the polymorphic loci DXS369, DXS296, DXS297 and DXS306 was carried out on a cohort of 17 families segregating for fragile X syndrome. The observed recombination fractions at: DXS369 (Zmax = 3.02; theta = 0.06), DXS297 (Zmax = 2.92; theta = 0.0), DXS296 (Zmax = 3.82; theta = 0.0), DXA306 (Zmax = 4.55; theta = 0.05) confirm that these loci are tightly linked to FRAXA. Our experience in the cytogenetic analysis of 58 at risk pregnancies by chorionic villus or fetal blood sample examination documents a false negative rate in obligate carrier male pregnancies for CVS of 11% and for FBS of 3%. PMID- 1415338 TI - Delayed replication of Xq27 in individuals with the fragile X syndrome. AB - The timing of late replicating bands on the X chromosome has been studied in individuals with the fragile X [fra(X)] syndrome. Compared to controls both affected individuals and symptomless carriers of the syndrome show delayed replication of the Xq27 region as shown by 2 different methods. The implications of this finding are discussed in relation to the proposal [Laird et al., 1987] that the fraX syndrome is associated with a failure to reactivate the Xq27 band correctly after it has been inactivated in a female. PMID- 1415340 TI - CNS midline anomalies in the Opitz G/BBB syndrome: report on 12 Brazilian patients. AB - We report on 12 Brazilian boys with the Optiz G/BBB syndrome associated with CNS midline anomalies, namely, Dandy-Walker anomaly (two patients), enlarged cisterna magna (four patients), enlarged 4th ventricle (four patients), and callosal a/hypoplasia (two patients). These signs clearly show the involvement of the CNS midline in the Opitz G/BBB syndrome. PMID- 1415339 TI - Oculoauriculovertebral anomaly: segregation analysis. AB - Seventy-four families of probands with oculoauriculovertebral anomaly were evaluated, including 116 parents and 195 offspring. Relatives were examined to identify ear malformations, mandibular anomalies, and other craniofacial abnormalities. For segregation analysis using POINTER, selection of the sample was consistent with single ascertainment. Different population liabilities were used for probands and relatives, because affection was narrowly defined for probands and broadly defined for relatives. The hypothesis of no genetic transmission was rejected. The evidence favored autosomal dominant inheritance; recessive and polygenic models were not distinguishable. PMID- 1415341 TI - Callosal agenesis, iris coloboma, and megacolon in a Brazilian boy with Rubinstein-Taybi syndrome. AB - We report on a Brazilian boy with Rubinstein-Taybi syndrome (RTS) with callosal agenesis, iris coloboma, and megacolon. To our knowledge, callosal agenesis, iris coloboma, and megacolon are unusual signs within the clinical spectrum of RTS, and the present association is apparently underscribed. PMID- 1415342 TI - Lacrimo-auriculo-dento-digital syndrome: evidence for lower limb involvement and severe congenital renal anomalies. AB - We describe a 3-generation family with lacrimo-auriculo-dento-digital syndrome (LADD). In addition to the well described abnormalities of ears, teeth, lacrimal apparatus and digits, the patients exhibit several previously undescribed anomalies, including minor facial anomalies (broad forehead, telecanthus, bulbous nasal tip, full jaw, ptosis and flared nostrils), involvement of the first and second toes, and congenital renal disease causing death in the neonatal period in 2 cases. PMID- 1415343 TI - Acrocallosal syndrome: report of a Brazilian girl. AB - We report on a Brazilian girl born to nonconsanguineous parents and presenting with frontonasal dysostosis, callosal agenesis, abnormal upper lids, cleft lip/palate, redundant skin in the neck, grooved chin, and bifid thumbs. Major diagnostic criteria present in this patient are related to the acrocallosal syndrome. The clinical and major nosologic aspects of this condition are discussed. PMID- 1415344 TI - Ophthalmological, skeletal, and cardiac abnormalities in sibs born to consanguineous parents: a new syndrome? AB - We report on a sibship from a consanguineous couple consisting of one boy with anophthalmia, one boy with buphthalmos and multiple congenital skeletal, muscle, and cardiac abnormalities, and a stillborn girl with anophthalmia and cardiac and skeletal abnormalities. A possible new syndrome of autosomal recessive inheritance and variable expressivity is discussed, comparing this report with others. PMID- 1415345 TI - Overlap between Majewski and hydrolethalus syndromes: a report of two cases. AB - We present 2 unrelated fetuses with manifestations of both the hydrolethalus syndrome and the short rib-polydactyly syndrome, type Majewski. It is proposed that cases of hydrolethalus syndrome with short limbs constitute a separate type of lethal osteochondrodysplasia mimicking short rib-polydactyly syndromes. PMID- 1415346 TI - King syndrome: a genetically heterogenous phenotype due to congenital myopathies. AB - We report on a patient with myopathy, kyphoscoliosis, joint contractures, and a facial appearance consistent with King syndrome. Unlike other reported cases, our patient had hyperextensible joints, normal stature, and pectus excavatum. The cardiac ventricles, aorta, and pulmonary artery were dilated. Malignant hyperthermia did not occur under anaesthesia although there was a transient increase in CK levels. Muscle bulk and tone were significantly decreased but collagen and elastin fibres were normal. The variable clinical presentation of King syndrome suggests that the manifestations are caused by different congenital myopathies and in all cases there is probably an increased risk of malignant hyperthermia. PMID- 1415347 TI - Clinical variability and genetic heterogeneity within the Acadian Usher population. AB - A number of Usher syndrome (USH) families are found among the French-Acadians living in southwestern Louisiana. These families are descended from a few common ancestors, suggesting that USH may be homogeneous within this ethnic group. However, we report distinct phenotypic variability. Based on differences in psychomotor development and tests of auditory and vestibular function, Acadian individuals with both USH Type 1 and Type 2 can be identified. One additional family, with unusual findings, represents a third clinical phenotype. Linkage data strongly support these clinical observations. PMID- 1415348 TI - Branchio-oto-renal syndrome: further delineation of an underdiagnosed syndrome. AB - We report on a woman who was diagnosed with branchio-oto-renal (BOR) syndrome after 2 pregnancies complicated by oligohydramnios due to renal hypoplasia and agenesis. Both babies died neonatally of pulmonary hypoplasia. Histopathology of the temporal bones of the second child showed marked immaturity of the middle ear cleft, ossicles, facial nerve and canal, and cochlear nerve. Maternal renal ultrasound study was normal although intravenous pyelography indicated renal hypoplasia. The frequency of BOR syndrome among cases of recurrent fetal renal hypoplasia/dysplasia or agenesis is unknown, and parental renal ultrasonography may not identify a heritable renal defect. Investigations should include a family history, and examination of relatives to look for preauricular pits, lacrimal duct stenosis, and branchial fistulae and/or cysts. Hearing studies and IVP may be indicated. PMID- 1415349 TI - New autosomal recessive syndrome of sparse hair, osteopenia, and mental retardation in Mennonite sisters. AB - We report on 2 Mennonite sisters with a syndrome of sparse hair, osteopenia, mental retardation, minor facial abnormalities, joint laxity, and hypotonia. Their asymptomatic consanguineous parents (inbreeding coefficient F = 1/64) have 6 other offspring, 3 of whom died in infancy of type II osteogenesis imperfecta (OI), and 3 of whom are normal. We analyzed collagens synthesized by cultured fibroblasts from these 2 sisters and their parents and detected no major abnormalities. Results of chromosomal and metabolic evaluations including amino acid analysis of plasma, urine, and hair were unremarkable. A literature search and survey of a computerized syndrome identification database did not disclose an identical phenotype. The sisters bear superficial resemblance to several known syndromes which we excluded on clinical and/or biochemical grounds. We conclude that they represent a new autosomal recessive syndrome, distinct from type II OI and perhaps unique to the Mennonite population or to this particular family. PMID- 1415350 TI - Weissenbacher-Zweymuller syndrome: a distinct autosomal recessive skeletal dysplasia. AB - The Weissenbacher-Zweymuller syndrome (WZS) is defined as congenital neonatal rhizomelic dwarfism with metaphyseal widening of the long bones and vertebral coronal clefts. Catch-up growth after 2-3 years is one of the striking manifestations. It is generally thought that WZS is a neonatal expression of the Stickler syndrome, even though in the latter, myopia, retinal detachment and a progressive metaphyseal dysplasia are characteristics that are not found in WZS. A critical analysis of all published patients with WZS in addition to 5 patients in 3 new families, shows that the WZS is a distinct syndrome of delayed skeletal maturation, different from the Stickler syndrome, and inherited as an autosomal recessive trait. The recognition of its unique characteristics has important implications in genetic counseling. PMID- 1415351 TI - Ullrich-Turner syndrome with a small ring X chromosome and presence of mental retardation. AB - Since some patients with Ullrich-Turner syndrome (UTS) have mental retardation, we reviewed our experience to look for a high-risk subgroup. Among 190 UTS and gonadal dysgenesis patients with X chromosome abnormalities, 12 had mental retardation. All of the six (100%) with a small ring X were educable (EMI) or trainable mentally impaired (TMI) with more severe delay than expected in UTS. Among the 184 with other X abnormalities, only 6 had similar delays (2 from postnatal catastrophes), for a frequency of 3.3% mental retardation among those without a small ring X; only 2.2% of these had unexplained mental retardation. Polymerase chain reaction studies showed no Y-derived material in the 2 patients who were evaluated, and in situ hybridization confirmed X origin of the ring in the 6 subjects who were evaluated. We describe the phenotype of the 6 individuals with a small ring X, and an additional 2 patients with a small ring X who were identified outside the survey. The subjects with a small ring X comprised a clinically distinct subgroup which had EMI/TMI and shorter stature than expected in UTS. Seizures and a head circumference less than 10th centile were observed in half of the patients with a small ring X, and strabismus, epicanthus, and single palmar creases were present in more than half. A "triangular" face in childhood, pigmentary dysplasia, sacral dimple, and heart defects were also common. Neck webbing appeared to be less frequent than in 45,X. We hypothesize that the high risk of mental retardation in this form of the UTS results from lack of lyonization of the ring X due to loss of the X inactivation center. Excluding those with a small ring X, mental retardation is not significantly increased in patients with UTS. PMID- 1415352 TI - Unrecognized pseudohyperkalemia as a cause of elevated potassium in patients with renal disease. AB - Pseudohyperkalemia, defined as serum to plasma potassium difference of more than 0.4 mmol/l, occurs when platelets, leukocytes or erythrocytes release intracellular potassium in vitro, leading to falsely elevated serum values. Pseudohyperkalemia has been observed in myeloproliferative disorders [1], including leukemia [2] and infectious mononucleosis [3] as well as in rheumatoid arthritis [4]. We present 2 patients with renal disease and thrombocytosis in whom pseudohyperkalemia was recognized only after common therapeutic measures and/or dialysis failed to effect a decrease in serum potassium. In patients with renal disease and thrombocytosis, plasma as well as serum potassium should be routinely measured prior to instituting aggressive therapy or altering dialysis prescription in order to avoid potentially dangerous overtreatment with resulting hypokalemia. PMID- 1415353 TI - Development of systemic lupus erythematosus in a patient on hemodialysis. AB - A case of systemic lupus erythematosus (SLE) that developed 2 years after beginning hemodialysis is reported. The patient had not been given any drug implicated in the production of SLE. She had been treated with deferoxamine, an in vitro inhibitory of DNA synthesis. The difficulty of the diagnosis is emphasized. Clinical improvement after prednisone treatment was impressive. SLE may appear even in patients receiving hemodialysis, despite immunological depression derived from chronic uremia. PMID- 1415354 TI - Compression of the left brachiocephalic vein by the innominate artery resulting in massive arm edema in a hemodialysis patient. AB - We report case of extrinsic compression of the left brachiocephalic vein by the innominate resulting in massive edema of the arm in a patient with hemodialysis Gore-Tex graft. To our knowledge, such phenomenon has not been previously reported. PMID- 1415355 TI - Successful resection of pheochromocytoma in a hemodialysis patient. AB - A 45-year-old woman with a pheochromocytoma who had been on regular hemodialysis for 4 years and underwent successful surgery is described. Careful preoperative management, including the use of prazosin and weight control, was carried out to prevent severe intraoperative and postoperative cardiovascular complications. Prazosin was given at an initial dose of 0.5 mg/day, and the dosage was increased to 20 mg/day prior to surgery. The increase in intravascular volume led to a gain of 3 kg in body weight. No deterioration of the cardiovascular or respiratory function was caused by these maneuvers, and surgery was performed without significant complications except for a rapid rise of blood pressure during tumor resection. To our knowledge, only one similar case report could be found in the English literature. PMID- 1415356 TI - Comparison between acetate and bicarbonate dialysis for the treatment of lithium intoxication. AB - Lithium is used to treat manic-depressive disorders, but toxic side effects commonly occur. The preferred treatment of severe lithium intoxication is hemodialysis. No data, however, exist comparing the effectiveness of acetate to bicarbonate dialysis for the removal of lithium. We present a case of lithium intoxication treated with both. During acetate dialysis, lithium removal occurred exclusively from the extracellular fluid space, while during bicarbonate dialysis, lithium removal occurred equally from both the extracellular and intracellular fluid spaces. We hypothesize that acetate but not bicarbonate activates the sodium-hydrogen antiporter on cell membranes, and that lithium, substituting for sodium, is driven into cells. This may explain the rebound in lithium levels commonly noted after conventional dialysis. We recommend bicarbonate hemodialysis as the therapy of choice for severe lithium intoxication. PMID- 1415357 TI - Immunoglobulin A nephropathy in a renal allograft of a black transplant recipient. AB - Although IgA nephropathy (IgA N) is reportedly the most common form of primary glomerulonephritis worldwide, there is a very low incidence of IgA N in Black Americans, and IgA N in Black patients with renal allografts has not been reported. In this report, we present the case of a Black patient with endstage renal disease presumed secondary to hypertensive nephrosclerosis who developed nephrotic range proteinuria due to IgA N in a cadaveric renal allograft 2 years following transplantation. Biopsy of the allograft in the immediate post transplantation period had revealed no evidence of IgA N. Chronic active hepatitis related to hepatitis C preceded the development of proteinuria by approximately 1 year, raising the possibility that IgA N in the renal allograft was secondary to the liver disease. The clinical and histological features of primary IgA N and IgA N secondary to liver diseases are discussed. PMID- 1415358 TI - Unilateral renal vein thrombosis and pulmonary embolism complicating membranous nephropathy. PMID- 1415359 TI - Whole blood serotonin levels are markedly elevated in patients on dialytic therapy. AB - The normal range for whole blood serotonin levels in chronic renal failure patients has not been defined. As serotonin may be implicated in platelet abnormalities, hypo- and hypertension and itch in dialysis patients, serotonin whole blood levels were measured in a group of patients with chronic renal failure and/or who were dialysis dependent. The levels were elevated in 12 patients with moderate (mean serum creatinine 335 +/- 54 mumol/l) chronic renal failure (270 +/- 46 micrograms/l) compared to 11 normals (163 +/- 17 micrograms/l, p less than 0.05; quoted normal range less than 300 micrograms/l) but did not correlate with serum creatinine levels. There was a marked elevation in serotonin levels in dialyzed patients, including those on hemodialysis (polysulfone, n = 6, 747 +/- 234 micrograms/l; cuprophane membranes, n = 6, 708 +/- 198 micrograms/l), hemodiafiltration (n = 12, 695 +/- 130 micrograms/l) and especially peritoneal dialysis (n = 6, 1,148 +/- 162 micrograms/l). All results were significant (p less than 0.01) compared to normals and compared to the nondialyzed group (p less than 0.05). The level of serotonin decreased during hemodialysis regardless of the membrane used. There was no positive correlation of serotonin levels with pruritus or hypertension, although there was a negative correlation with systolic blood pressure. The reference range for serotonin whole blood levels needs to be broadened when considering dialyzed patients. PMID- 1415360 TI - Early diagnosis of gram-negative peritonitis in continuous ambulatory peritoneal dialysis patients with the Lymulus amebocyte lysate assay. AB - The treatment of peritonitis in continuous ambulatory peritoneal dialysis patients is empiric until the bacteriological results are available. The Lymulus amebocyte lysate assay (LAL) is a very sensitive method for the detection of endotoxin, a structural component of gram-negative bacteria. We performed the LAL assay in a prospective study in 36 consecutive episodes of peritonitis. The LAL assay was positive in all 10 episodes of gram-negative peritonitis (100% specificity). Treatment directed specifically against gram-negative or -positive infection was started based on the LAL assay result. In 26 episodes with LAL negative test, a gram-positive bacterium was cultured in 23 episodes, in 1 there was fungal infection and 2 were sterile. In summary: the LAL assay is a rapid (1 h) and sensitive method for the differentiation of gram-positive or -negative peritonitis and enables starting an immediate and more appropriate antibiotic therapy. PMID- 1415361 TI - Comparative study of IgA nephropathy with acute and insidious onset. Clinical, laboratory and pathological findings. AB - In order to clarify the difference of clinical and pathological features between the IgA nephropathy patients with acute and insidious onset, 427 patients were examined in this study. Seventy-eight patients with acute onset (group 1) were often associated with mucosal system infections at the abrupt onset. This group revealed macroscopic hematuria, more severe microscopic hematuria (more than 20/hpf), higher glomerular filtration rate (p less than 0.01) and lower serum levels of C3 (p less than 0.01). It had also a significantly higher incidence of exudative lesions (p less than 0.001). On the other hand, the onset of 349 patients (group 2) was noticed to be insidious without preceding infections. This group showed a more severe increase in mesangial cells (p less than 0.01) and a significantly higher incidence of adhesion, arterial sclerosis and tubulointerstitial changes. Deposition of Clq, C4 and IgM and detachment of visceral epithelium from the basement membrane were more frequently seen in group 2. Twenty-seven of 345 patients followed for at least 1 year after the biopsy were on maintenance hemodialysis: 1 patient was in group 1 and 26 were in group 2. These results clarified that there was a difference in clinical, laboratory and histopathological findings between the patients with IgA nephropathy with acute and insidious onset. PMID- 1415362 TI - Effect of dialyzer reprocessing with Renalin on serum beta-2-microglobulin and complement activation in hemodialysis patients. AB - The peracetic acid-based sterilant Renalin is increasingly being used for reprocessing hemodialyzers. In order to evaluate the effects of reprocessing on beta 2-microglobulin (beta 2M) kinetics and complement activation in chronic hemodialysis patients, we compared 4 dialyzer membranes on 1st, 2nd and 4th use of the membrane. Dialysis with new cuprammonium rayon dialyzers (0.8 m2) for 4 h resulted in a nonsignificant increase in serum beta 2M concentrations of 10.7% (corrected for changes in extracellular volume) and significant generation of the complement component C3a des Arg. On reuse, minimal changes in serum beta 2M levels were noted and complement activation was absent. Dialysis with new cellulose acetate (CA, 1.5 m2), polyacrylonitrile (AN69 HF, 1.6 m2) or polymethylmethacrylate (PMMA, 1.6 m2) membranes resulted in significant decreases in serum beta 2M levels (19.5, 31.7 and 50.8%, respectively). Reprocessing had negligible effects on the removal of beta 2M by CA and AN69, but by the 4th use halved the effectiveness of PMMA. Reprocessing reduced the significant generation of C3a des Arg observed with new CA and PMMA membranes. We conclude that, except for PMMA, Renalin reprocessing has minor effects on the ability of the membranes to remove beta 2M and improves the biocompatibility of all membranes studied. PMID- 1415363 TI - Effect of erythrocyte deformability on renal hemodynamics and plasma renin activity. AB - Increased blood viscosity has been previously noted in a subgroup of patients with essential hypertension with concomitant high plasma renin activity (PRA). It has been suggested that the cause of hyperviscosity in hypertensives is the presence of circulating red blood cells (RBCs) that were rendered less deformable by significant alterations in their cationic milieu, namely an increase in intracellular concentration of calcium and sodium. The relation between RBC deformability and PRA however is not clear. Our study was conducted to examine this issue. RBC deformability was reduced experimentally, and its effects on renal blood flow, renal artery resistance, glomerular filtration rate and PRA were investigated in experimental (n = 8) and control (n = 4) groups of dogs. Blood was collected from the animals before the experiments and incubated with 0.025% glutaraldehyde. These hardened RBCs were administered to the animals through exchange transfusions. Following the exchange transfusion with the hardened RBCs, there were no changes in renal blood flow, renal artery resistance, and the creatinine clearance. The only change observed was an increase in PRA. In the control group, all parameters that were determined remained unchanged. The data are consistent with the notion that the presence of circulating hardened RBCs may by itself increase PRA, and this effect can be important in some types of hypertension and some other disorders in which impaired deformability of RBCs have been reported. PMID- 1415364 TI - Volumetric analysis of urinary erythrocytes: a standardized methodology to localize the source of haematuria. AB - Volumetric analysis of urinary red blood cells (RBCs) was performed in two groups of patients: (a) 91 with glomerulonephritis (GN), 158 with non-glomerular diseases (non-GN) and 53 controls without haematuria; (b) 97 with GN and 41 with non-GN diagnoses and greater than or equal to 2+ haematuria, analysed after modified sample preparation (isotonic dilution and haemolysis to eliminate non RBC debris). In group A, diagnostic ranges were established for modal, mean and differential (urinary-peripheral blood modal) RBC volumes to differentiate GN from non-GN sources of blood loss according to RBC size. 54% (135/249) of modal volumes and 68% (124/183) with greater than or equal to 2+ haematuria were within a diagnostic range of values, i.e. 40-180 fl (sensitivity), and the source of haematuria was correctly identified in 85% (115/135) and 87% (108/124) of these, respectively (specificity). Of the remainder, with modal volumes less than 40 or greater than 180 fl, 45% (51/114) were from GN and 55% (63/114) from non-GN specimens, along with 94% (48/53) controls without haematuria (non-diagnostic analyses). In contrast, whilst 90% (74/82) of mean volumes greater than or equal to 110 fl and 94% (62/66) of differential volumes greater than or equal to 0 fl were from non-GN specimens, values below these were common to both diagnostic groups so that diagnostic sensitivities were reduced to 38% (82/219) and 34% (66/193), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415365 TI - Fractional excretion of urea as a guide to renal dysfunction. AB - The use of fractional excretion of sodium as a guide to renal perfusion is hampered by the prior use of natriuretic agents. The fractional excretion of urea (FEUr) has been shown to be affected by volume status. We, therefore, determined the value of the FEUr as a guide to renal perfusion. In 6 patients evaluated prospectively and in 87 patients evaluated retrospectively, a low FEUr (less than or equal to 35%) was found to be a sensitive index to renal perfusion, despite the prior administration of furosemide. PMID- 1415366 TI - Once weekly versus twice weekly subcutaneous administration of recombinant human erythropoietin in haemodialysis patients. AB - Optimal route and frequency of administration of recombinant human erythropoietin (rHuEPO) have not yet been determined. There is some evidence to suggest that subcutaneous administration of rHuEPO may be more effective than the intravenous route in reversing renal anemia. It is also unclear whether rHuEPO is more effective when given by a large intermittent dose or by more frequent multiple divided doses. We have compared the effect of twice weekly versus once weekly subcutaneous administration of rHuEPO in two groups of haemodialysis patients. At the end of 12 weeks of treatment with rHuEPO, the mean haemoglobin levels had risen from 6.9 +/- (SD) 0.7 to 8.9 +/- 1.3 g/dl in the once weekly group and from 7.2 +/- 1.0 to 9.3 +/- 1.6 g/dl in the twice weekly group. The average doses of rHuEPO used during the study were 127 +/- 6 and 115 +/- 18 U/kg body weight/week for the once weekly and twice weekly groups, respectively. Subcutaneous administration of low-dose rHuEPO is effective in reversing renal anaemia. Similar responses were obtained with once weekly and twice weekly regimens. PMID- 1415367 TI - Effect of amino acid based dialysis solution on peritoneal permeability and prostanoid generation in patients undergoing continuous ambulatory peritoneal dialysis. AB - The acute effect of amino acid based dialysis solution on peritoneal kinetics of amino acids and plasma proteins in comparison to conventional glucose-based dialysate was studied in 9 patients with end-stage renal failure on continuous ambulatory peritoneal dialysis. Instillation of 2.6% amino acid solution resulted in raised plasma concentrations of all essential amino acids included in the dialysis fluid (p less than 0.005). The amino acid solution induced an augmented leakage of plasma proteins into the dialysate at all dwell times investigated (1 8 h). After a dwell time at 8 h, the dialysate total protein increased from 2.62 +/- 0.45 g with glucose dialysate to 3.85 +/- 0.42 g with amino acid solution (p less than 0.05). Corresponding results were obtained for beta 2-microglobulin, albumin, transferrin, IgG, and for the non-essential amino acids alanine, citrulline, and glutamine (p less than 0.025) not included in the initial amino acid composition of the dialysis fluid. During the use of amino acid based dialysis fluid, the effluent prostaglandin E2 concentration increased by more than 80% in comparison to glucose dialysate (p less than 0.025). The augmented loss of proteins induced by the amino acid solution was positively correlated with increased dialysate prostaglandin E2 (r = 0.8894; p less than 0.001). Peritoneal ultrafiltration was not affected by the use of amino acid based dialysate fluid. The present results indicate that amino acid based dialysis fluid enhances the peritoneal permeability for plasma proteins and amino acids, probably mediated by locally generated prostanoids. PMID- 1415368 TI - Pain at the injection site of subcutaneously administered erythropoietin in maintenance hemodialysis patients: a comparison of two brands of erythropoietin. AB - Local pain due to subcutaneous erythropoietin (EPO) injection into the thigh was studied using a verbal score ranging from 0 to 4. Equivoluminous doses of epoetin alpha (Cilag) and epoetin-beta (Boehringer) were compared in 2 controlled single blind experiments: 10 dialysis patients were treated at random for 4 weeks at consecutive sessions with both brands of EPO, and 40 patients were treated in 1 session only with the 2 brands simultaneously. Pain scores were 1.12 +/- 0.28 versus 0.15 +/- 0.06 (p less than 0.05) and 1.75 +/- 0.19 versus 0.08 +/- 0.04 for epoetin-alpha and epoetin-beta, respectively (p less than 0.001). Treatment acceptance was 48% for epoetin-alpha versus 83% for epoetin-beta (p less than 0.05). PMID- 1415369 TI - Abnormalities of thirst regulation in patients with chronic renal failure on hemodialysis. AB - To determine whether thirst mechanisms are altered in nondiabetic patients with chronic renal failure on hemodialysis, 4 patients with an average weight gain between dialysis sessions of more than 5% of dry body weight (group I), 5 patients with less than 3% weight gain (group II), and a group of 6 healthy subjects (group III) were submitted to infusion of hypertonic saline. After infusion the subjects had free access to water. Thirst was evaluated by visual analogue rating scales. Despite similar increments of effective plasma osmolality during saline infusion, patients of group I were thirstier than groups II and III (p less than 0.005 and p less than 0.01, respectively). Changes in thirst ratings were similar in groups II and III. Osmotic thresholds for thirst onset were similar in groups II and III (288.9 +/- 8.5 and 289.8 +/- 3.4 mosm/kg, respectively), but lower in group I (277.6 +/- 7.6 mosm/kg). Nevertheless, great variations were observed in the latter group. Thus, 2 patients showed thresholds for thirst within the normal range, whereas the others had low osmolar thresholds for thirst and baseline plasma osmolalities and high basal thirst scores. During the drinking period, the patients of group I drank more (14.2 +/- 2.8 ml/kg) than those of groups II (5.3 +/- 1.6 ml/kg; p less than 0.02) and III (10.2 +/- 1.6 ml/kg; n.s.) The plasma levels of angiotensin II in uremic patients were higher than in healthy subjects, although there were no differences between groups I and II and no correlation between basal angiotensin II levels and the interdialytic weight gain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415370 TI - Inhibition of cytokine synthesis by peritoneal dialysate persists throughout the CAPD cycle. AB - The current study focused on the effect of continuous ambulatory peritoneal dialysis (CAPD) dialysate obtained following different intraperitoneal dwell periods on the release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha) from mononuclear leukocytes (PBMC). Aliquots of 5 x 10(6)/ml healthy peripheral PBMC were exposed to fresh or spent CAPD dialysate (10-240 min of intra-peritoneal dwell) and stimulated with Escherichia coli endotoxin (10 micrograms/ml, 2h). IL-6 and TNF alpha in cell supernatants were determined by specific enzyme immunoassays. Control PBMC in physiological buffer released 361 +/- 70 pg/ml IL-6 and 717 +/- 147 pg/ml TNF alpha (mean +/- SEM, n = 8), whereas exposure to fresh dialysis fluids severely suppressed cytokine release from PBMC (less than 30 pg/ml IL-6 and less than 15 pg/ml TNF alpha). A significant inhibition of IL-6 and TNF alpha release was also observed in PBMC exposed to spent dialysate. The inhibitory capacity of the spent fluids was pronounced with increasing intra-peritoneal dwell time (10 min: 183 +/- 45 pg/ml IL-6 and 538 +/- 109 pg/ml TNF alpha; 240 min: 26 +/- 5 pg/ml IL-6 and 105 +/- 30 pg/ml TNF alpha; mean +/- SEM, n = 16). These data indicate that the impairment of cell responsiveness following exposure of PBMC to peritoneal dialysate is not restricted to the unused fluids, but is also observed following intra-peritoneal equilibration. Moreover, our findings suggest the presence of cytokine inhibitory factors in the peritoneal dialysate of CAPD patients which appear to accumulate in the peritoneal effluent during the CAPD cycle. PMID- 1415371 TI - Effect of hypercalcemia on renal sympathetic nervous system activity. AB - Since calcium plays a modulatory role in the activity of the sympathetic nervous system (SNS), in these studies, we have tested the hypothesis that hypercalcemia may alter renal SNS activity, and, consequently, renal function. Acute hypercalcemia was induced in Sprague-Dawley rats by infusion of calcium 30 mg/kg/2 h in 0.45% saline. A control group of rats received only 0.45% saline. Two more groups of rats received either calcium or 0.45% saline 7-10 days after total renal denervation. Calcium infusion increased serum calcium by 1.8 +/- 0.23 mg/dl in rats with intact renal nerves and by 2.7 +/- 0.48 mg/dl in renal denervated rats. Mean arterial pressure and inulin clearance did not change during calcium or 0.45% saline in rats with intact renal nerves. Renal sympathetic nerve activity (RSNA) decreased by 44% in rats infused with calcium, but it did not change in control animals. Calcium caused a significantly greater rise in urine volume, sodium excretion and fractional excretion of sodium than the infusion of 0.45% saline. Rats with renal denervation manifested greater baseline urine volume, sodium excretion and fractional excretion of sodium than rats with intact renal nerves. Infusion of calcium, however, caused no further rise in urine sodium excretion in these animals. alpha-Methyltyrosine, an inhibitor of norepinephrine (NE) synthesis, also increased natriuresis in rats. Calcium reduced by 27% the NE content in the kidney but not in the heart. Methyltyrosine, on the other hand, reduced NE content in both the heart and the kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415372 TI - Uremic inhibitors of erythropoiesis: a study during treatment with recombinant human erythropoietin. AB - The effects of increasing amounts of uremic sera (US) on the growth of erythroid progenitor cells [burst-forming unit erythroid (BFU-E)] collected from peripheral blood of normal subjects were evaluated to assess the potential role of uremic inhibitors of erythropoiesis during a treatment with recombinant human erythropoietin (r-HuEpo). US were collected from 8 patients on regular dialysis with marked anemia (Hb 6 +/- 0.5 g%) before and after a treatment with high doses of r-HuEpo (from 300 to 525 U/kg/week). Standard cultures for BFU-E were performed in alpha-metylcellulose with fetal calf serum (FCS) and 4 U/ml of r HuEpo (Cilag, Ortho). In successive cultures, US were added at increasing amounts to the standard culture in order to assess a possible inhibitory effect on BFU-E growth. Finally, in order to assess a possible lack of stimulatory factors, we partially substituted FCS with US. The addition of US collected either before or after therapy with r-HuEpo to the standard culture had no effect on the growth of BFU-E. Vice versa, the number of cultured BFU-E decreased when FCS was partially substituted with US collected before r-HuEpo. This effect was not evident when FCS was partially substituted with US collected after r-HuEpo. No significant differences were recorded in the tested sera collected before and after therapy considering erythropoietin levels and amino acid levels. We hypothesized that some other factors with erythropoietic stimulatory activity (burst-promoting activity?) may be deficient in uremic patients with marked anemia and can be induced during therapy with r-HuEpo. PMID- 1415373 TI - Origins of nephrology: the 17th century. I. The fallacies deriving from examination of the urine according to James Primrose. PMID- 1415374 TI - Long-term immunogenicity and efficacy of hepatitis B vaccine in hemodialysis patients. AB - Although the efficacy of hepatitis B vaccines in patients under chronic hemodialysis treatment has been well documented, the persistence of immunity in this population remains largely unknown. In this study we have followed 60 hemodialysis patients up to 3 years after primary hepatitis B vaccination (four doses of recombinant hepatitis B vaccine; Engerix B, 20 mg/dose) to evaluate the persistence of immunity (as indicated by serum levels of antibody to hepatitis B surface antigen-anti-HBs-higher than or equal to 10 mIU/ml). Fourty-four (73%) patients developed anti-HBs levels above 10 mIU/ml after vaccination; the remaining 16 (27%) vaccinees were considered nonresponders and were given a booster dose that again failed to elicit an immunoresponse. After 3 years of follow-up, 18 out of 44 (41%) responders had no detectable anti-HBs levels in the serum (antibody loss occurring within 8 and 12 months in 3 cases, within 1 and 2 years in 13, and within 2 and 3 years in 2 other cases). When compared with the responders that lost their antibodies during the follow-up period, those who remained immunoreactive 3 years after vaccination was initiated were younger and had higher anti-HBs levels at 8 months of follow-up. Two hepatitis B virus infections were detected among nonresponders during the follow-up period. Based on these data, we conclude that patients undergoing chronic hemodialysis therapy not only have lower response rates to hepatitis B vaccination than healthy adults, but also that these are frequently transient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415375 TI - Triiodothyronine stimulates growth of peripheral blood mononuclear cells in serum free cultures in uremic patients. AB - The effect of triiodothyronine (T3) on the responses to mitogens and on the production of prostaglandin E2 and interleukin 2 were studied in serum-free cultures of peripheral blood mononuclear cells (PBMC) in 20 patients undergoing hemodialysis and in 30 control subjects. T3 increased the growth of PMBC induced by phytohemagglutinin and pokeweed mitogen in both groups. PBMC reached growth maximum at 0.5 nM T3 when stimulated by phytohemagglutinin in both groups. At higher concentrations of T3 the effect declined in the control group, but the response of uremic PBMC was constant. The response to T3 of pokeweed mitogen stimulated PBMC was lower in the uremic patients. The production of prostaglandin E2 by PBMC was higher in the uremic patients than in the controls. T3 had no effect on prostaglandin E2 production. Indomethacin alone and in combination with T3 had a stimulatory effect on cell growth in the patient group. T3 had no effect on the release of interleukin 2 by PBMC. An additive effect of interleukin 2 and T3 was observed in cultures stimulated by suboptimal concentrations of the mitogens. In conclusion, the impaired growth of PBMC in serum-free cultures from uremic patients was enhanced, however, not normalized, by external addition of T3, inhibition of prostaglandin E2 synthesis, and addition of interleukin 2. PMID- 1415376 TI - Crescentic glomerulonephritis in children: a review of 43 cases. AB - Forty-three children with crescentic glomerulonephritis (GN), having large crescents in more than 50% of the glomeruli, were observed during a period of 22 years. There were 17 boys and 26 girls between the ages of 3.5 and 14 years (mean 8.7 +/- 2.6). Thirty-one patients (72%) presented with acute nephritic features and increasing renal insufficiency (rapidly progressive GN) whereas 12 had an insidious onset with nephrotic syndrome, or rarely with nonspecific symptoms. Eleven patients had evidence of poststreptococcal GN and 6 an underlying systemic disorder. Renal biopsy showed large crescents in greater than 80% of the glomeruli in 38 cases (100% in 28) which were predominantly fibrocellular or fibrous in 80% of the patients. Nineteen patients (44%) were treated with prednisolone, cyclophosphamide and dipyridamole; in addition, 8 were also given anticoagulants. Six patients received pulse doses of corticosteroids. In 23 patients, there was inexorable progression of renal failure, 14 showed partial improvement but subsequently had varying degrees of renal insufficiency and in 6, there was recovery of renal function with normal levels of serum creatinine. Of the latter, 4 had received immunosuppressive anticoagulant therapy and 2 only supportive care. Of 11 patients with poststreptococcal crescentic GN, 7 progressed to end-stage renal disease and 2 developed chronic renal insufficiency. Our findings confirm the poor outcome of crescentic GN in children, irrespective of the underlying etiology. In a small proportion of cases, the disorder may have an insidious onset and a slowly progressive course, but an equally grave prognosis. PMID- 1415377 TI - Subjective quality of life assessment in hemodialysis patients at different levels of hemoglobin following use of recombinant human erythropoietin. AB - The quality of life of 12 hemodialysis (HD) patients was assessed in a prospective, blinded, cross-over fashion before treatment with recombinant human erythropoietin (r-HuEPO) and at two different levels of hemoglobin (Hb, 9 and 12 g/dl) by means of an interviewer-based questionnaire, the sickness impact profile (SIP). Patients were matched into two groups with no significant difference for age, weight, Hb (6.3 +/- 0.5, mean +/- SEM, group A, vs. 6.4 +/- 0.9 group B), length of hemodialysis or number of years of prior transplantation. SIP was assessed prior to treatment, after reaching the first target Hb (Hb 9 g/dl group A, 12 g/dl group B), after 4 months at that target Hb and after 4 months at the alternative target Hb for each group. For all patients, there was a highly significant improvement in quality of life as assessed by lower SIP scores between the initial and second assessments. This was evident for the physical (8.9 +/- 1.4 vs. 2.8 +/- 1.0; p less than 0.001) and psychosocial (14.9 +/- 3.9 vs. 4.4 +/- 1.1; p less than 0.01) dimensions. Total scores (16.3 +/- 2.4 vs. 5.7 +/- 0.9; p less than 0.001) showed similar changes, reflecting significant improvement in 10 of 12 possible categories between the first two assessments (p less than 0.05 to p less than 0.001). Improved scores were maintained but did not change appreciably after the 2nd assessment. There was no significant difference in any score (category, dimensional or total) obtained after 4 months at Hb 9 g/dl compared to those after the same period at Hb 12 g/dl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415378 TI - Effect of exercise training on glomerular filtration rate of mice with various degrees of renal mass reduction. AB - We studied the effect of repeated heavy physical activity on glomerular filtration rate (GFR) in healthy, uninephrectomized and experimentally uremic mice. Exercise consisted of running uphill in the inner surface of a rotating cylinder in ideal environmental temperature. In the control groups, no extra physical activity was imposed. In sham-operated and nephrectomized mice, GFR rose significantly following training. By contrast, GFR did not change significantly in the exercised mice with experimental renal failure 24 h following the last exercise session. During the same period, no significant change was observed in GFR of any of the control groups. Following training in each experimental group, mean aortic blood pressure as well as fractional kidney weight (kidney weight/body weight) were not different from the respective controls. Our results indicate that the capacity to augment GFR by physical training is dependent upon the amount of remaining functional renal tissue. PMID- 1415379 TI - Erythropoietin resistance due to vitamin B12 deficiency. Case report and retrospective analysis of B12 levels after erythropoietin treatment. AB - We describe the first reported case of resistance to human recombinant erythropoietin (rhEPO) treatment caused by vitamin B12 deficiency in a chronic hemodialysis patient. Despite a normal B12 level before rhEPO treatment, resistant anemia together with a low B12 level and a megaloblastic bone marrow developed after only 8 months of rhEPO. There was a rapid reticulocyte response to B12 supplements, and transfusion requirements dropped from 2 units monthly to nothing. Atrophic gastritis was diagnosed through endoscopy and biopsy. Because of the fall in B12 level after 8 months of rhEPO treatment, we analyzed the results of routinely measured B12 levels in 30 hemodialysis patients treated with rhEPO, and found the mean B12 levels to be unchanged before and after rhEPO treatment. Although we found screening for B12 deficiency of little benefit, any patient with rhEPO resistance should have B12 levels tested, given the potentially serious extra-hematological effects of B12 deficiency. PMID- 1415380 TI - Hemolytic-uremic syndrome associated with ingestion of quinine. AB - Hemolytic-uremic syndrome following quinine ingestion is a newly described phenomenon, with just two previous descriptions of 4 cases in the literature. We describe a 5th case. The reaction may be mediated by the presence of antibodies reactive against platelets in the presence of quinine. Treatment has included use of plasma exchange, prednisone, aspirin, and dipyridamole. The patients have all regained some degree of renal function. However, it is unclear whether pharmacological treatment or spontaneous resolution is responsible for the improvement. Quinine-associated hemolytic-uremic syndrome probably occurs more often than is recognized. It is important to recognize this reaction when it occurs and to avoid further quinine exposure, since the reaction seems to be recurrent. PMID- 1415381 TI - Christian Friedrich Schonbein (1799-1868): from the perilous explosive guncotton to the salutary dialysis membranes. PMID- 1415382 TI - Delayed infectious complications of peritoneal dialysis catheters. PMID- 1415383 TI - Screening for congenital heart disease with the four-chamber view of the fetal heart. AB - OBJECTIVE: Our objective was to determine the efficacy of the four-chamber view of the fetal heart in routine ultrasonographic examination as a screening tool for congenital heart defects. STUDY DESIGN: A prospective cohort study compared the detection rate of congenital heart defects among 5336 pregnant women screened with the ultrasonographic four-chamber view of the fetal heart from 1987 through 1989 with that among 3680 patients examined ultrasonographically without the four chamber view during the 2 preceding years (1985 through 1986). All patients were followed until delivery or termination of pregnancy, and clinical or autopsy confirmation of prenatal findings were obtained on all cases. RESULTS: The overall incidence of congenital heart diseases was 5.2 per 1000 (47/9016). During the years 1985 through 1986 15 neonates with congenital heart diseases were identified, seven of which were prenatally diagnosed (sensitivity 43%). During the period 1987 through 1989 a four-chamber view of the fetal heart was obtained in 95% of cases; 32 cases of congenital heart disease occurred, 26 of which were diagnosed antenatally (sensitivity 81%; p = 0.01). Two false-positive diagnoses were made during the second time period, giving a specificity of 99.9%. CONCLUSION: The four-chamber view of the fetal heart is easily obtained, does not significantly increase the duration of a routine ultrasonographic examination, and has an excellent sensitivity for the identification of congenital heart diseases. PMID- 1415384 TI - Transverse cerebellar diameter in twin gestations. AB - OBJECTIVE: The purpose of this study was to evaluate the significance of transverse cerebellar diameter measurements in twin pregnancies. STUDY DESIGN: A prospective, cross-sectional ultrasonographic study was done on 329 normal singleton fetuses and 47 normal twin pairs. Fetal biometric measurements including biparietal diameter, head circumference, abdominal circumference, femur length, and transverse cerebellar diameter were compared between concordant (n = 13) and discordant (n = 11) twins. RESULTS: (1) There was no significant difference in transverse cerebellar diameter measurements between normal singleton and twin gestations. (2) There was no significant difference in transverse cerebellar diameter measurements in each twin pair. (3) Transverse cerebellar diameter was unaffected by the chorionicity or discordancy. (4) Predicted gestational age by transverse cerebellar diameter nomogram for singletons provided satisfactory correlation for twins. CONCLUSION: Transverse cerebellar diameter may be a useful predictor of gestational age and may be independent of discordant growth in twins. PMID- 1415385 TI - Fetuses with Down syndrome have disproportionately shortened frontal lobe dimensions on ultrasonographic examination. AB - OBJECTIVE: The purpose of our study was to determine whether the frontal lobe is significantly smaller than normal in the Down syndrome fetus in midtrimester. STUDY DESIGN: Frontothalamic distance, measured from the inner table of the frontal bone to the posterior thalamus, and frontothalamic distance/biparietal diameter ratio were compared in 125 normal and 19 Down syndrome fetuses between 16 and 21 weeks' gestation. RESULTS: In the Down syndrome group 52% had frontothalamic distance < 10th percentile. When the frontothalamic distance and the frontothalamic distance/biparietal diameter ratio were expressed as multiples of the normal median to eliminate variation caused by gestational age, the mean value of multiples of the median in Down syndrome fetuses was compared with the mean value of multiples of the median in normal fetuses and was found to be significantly smaller (p < 0.0019 and p < 0.0177, respectively). When an observed to-expected frontothalamic distance ratio of < or = 0.84 is used as a cutoff to screen for Down syndrome, sensitivity, specificity, and positive predictive values of 21.2%, 95.2%, and 1.2%, respectively, are achieved in a population with a 1:270 risk. CONCLUSION: Frontal lobe dimension is significantly shortened in Down syndrome fetuses. PMID- 1415386 TI - The effect of improvement of umbilical artery absent end-diastolic velocity on perinatal outcome. AB - OBJECTIVES: The purpose of this study was to analyze cases in which antenatal improvement of absent fetal umbilical artery end-diastolic velocity was detected and to correlate improvement with perinatal outcome. STUDY DESIGN: Forty cases of umbilical artery absent end-diastolic velocity in singleton pregnancies were retrospectively reviewed. Maternal characteristics and perinatal outcomes were compared in cases where improvement of end-diastolic velocity was diagnosed and those in which no improvement was detected. RESULTS: Eleven cases of absent end diastolic velocity showed antenatal improvement and were associated with more advanced gestational age at delivery, longer diagnosis-to-delivery interval, larger birth weights, and a lower incidence of neonatal death than those fetuses without antenatal improvement. CONCLUSION: Improvement of umbilical artery absent end-diastolic velocity can occur and is associated with improved pregnancy outcome when compared with patients without antenatal improvement of diastolic velocity. PMID- 1415387 TI - The influence of the post-Chernobyl fallout on birth defects and abortion rates in Austria. AB - OBJECTIVES: We analyzed the influence of the radioactive fallout after the Chernobyl disaster on the rate and regional distribution of birth defects and abortion rates in southern Austria. STUDY DESIGN: During 1985 to 1989 a total of 66,743 births was monitored. Twelve sources provided data on 1695 cases of birth defects, 1579 of which were suitable for analysis. All cases were analyzed in terms of their calculated conception date and divided into three main groups according to their vulnerable phase of embryogenesis, spermatogenesis, and oogenesis. To study possible regional changes, the findings were plotted in 17 political subdistricts. The overall abortion rate and the counseling frequency at termination clinics was determined. RESULTS: No significant changes in the incidence of birth defects, abortion rate, or counseling rate at pregnancy termination clinics were observed. CONCLUSIONS: Assessing the teratologic potential of low-dose radiation is difficult and requires adequate grouping of birth defects, sufficient baseline data, and highly reliable registries. PMID- 1415388 TI - Outcome of antenatally diagnosed cystic adenomatoid malformations. AB - OBJECTIVE: Twenty-two cases of antenatally diagnosed congenital cystic adenomatoid malformations are reported. STUDY DESIGN: Case management is reviewed. RESULTS: Eighteen women continued pregnancy after diagnosis. In nine cases nonimmune hydrops fetalis did not develop and all infants survived. Nonimmune hydrops fetalis developed in the other nine; fetal intervention was performed in eight cases. In the single case of nonimmune hydrops fetalis without intervention, the neonate died. In four cases aspiration of macrocystic lesions was performed. In two cases cystoamniotic shunts were placed. Neither aspiration or shunting provided long-term benefit. In six cases fetal lobectomy was ultimately performed and four survived. Two fetuses did not undergo in utero surgery; one was delivered prematurely after cyst aspiration and lived, and the other previable fetus was delivered soon after shunting. CONCLUSIONS: Fetal survival is best related to development of nonimmune hydrops fetalis. Aspiration of cystic lesions and cystoamniotic shunts generally provide short-term benefit. Early experience with fetal surgery for congenital cystic adenomatoid malformations has been encouraging. PMID- 1415389 TI - The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice. AB - OBJECTIVES: Interleukin-1 has been implicated in the mechanisms responsible for preterm parturition in the setting of intrauterine infection. This cytokine is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and induces preterm parturition in mice. The purpose of this study was to determine whether pretreatment with the natural interleukin-1 receptor antagonist can block interleukin-1-induced preterm parturition in mice. STUDY DESIGN: Balb/CJ female mice impregnated by B6D2 F-1 male mice were randomly allocated to one of the following treatment groups: (1) saline solution (n = 15), (2) human recombinant interleukin-1 alpha or human recombinant interleukin-1 beta (n = 12), (3) human recombinant interleukin-1 receptor antagonist (n = 13), and (4) human recombinant interleukin-1 receptor antagonist plus human recombinant interleukin-1 (n = 24). RESULTS: An interleukin-1 dose of 10 micrograms per mouse induced preterm parturition in all cases. Pretreatment with interleukin-1 receptor antagonist (dose 1 mg per animal) prevented interleukin-1-induced preterm parturition. Interleukin-1 receptor antagonist administration was not associated with demonstrable side effects including behavioral changes, vaginal bleeding, duration of pregnancy, and pregnancy outcome. CONCLUSION: Our results suggest that interleukin-1-induced preterm delivery in mice is mediated by the interleukin-1 receptor. PMID- 1415390 TI - Study of thromboxane and prostacyclin metabolism in an in vitro model of first trimester human trophoblast. AB - OBJECTIVES: The purpose of our study was to establish an in vitro tissue culture system to study eicosanoid metabolism in first-trimester trophoblastic tissue. Thromboxane A2, a potent vasoconstrictor, and prostacyclin, a potent vasodilator, were analyzed to evaluate their production in early pregnancy. STUDY DESIGN: Trophoblastic tissue was obtained via transabdominal chorionic villous sampling from 33 pregnancies at 9 to 12 weeks' gestation for cytogenetic diagnosis. Initially, tissue obtained from the cytogenetics lab was morphologically consistent with villous core cells. Through altering cell density and passage, the cells became morphologically consistent with cytotrophoblasts. The cell lines were exposed to arachidonic acid (50 mumol/L) and aspirin (1 to 100 mumol/L) for 24 hours. Thromboxane B2 and 6-keto prostaglandin F2 alpha were measured by radioimmunoassay. RESULTS: Villous core cells and cytotrophoblasts increased production of thromboxane A2 and prostacyclin in the presence of arachidonic acid (p < 0.002). The villous core cells produced more thromboxane A2 and prostacyclin than cytotrophoblasts (p < 0.02). A significant inhibition of both thromboxane A2 and prostacyclin production was seen in the presence of 100 mumol/L aspirin in both cell types (p < 0.05). CONCLUSIONS: This model may be useful for studying placental function in the first trimester because individual placental compartments can be evaluated in tissue culture. At the cellular level we were not able to detect a preferential decrease in thromboxane A2 production in the presence of aspirin (1 to 100 mumol/L). PMID- 1415391 TI - Endothelium-derived relaxing factor inhibition augments vascular angiotensin II reactivity in the pregnant rat hind limb. AB - OBJECTIVE: The purpose of our study was to determine whether endothelium-derived relaxing factor plays a role in the blunting of maternal vascular reactivity in pregnancy. STUDY DESIGN: We measured the concentration-pressor responses to norepinephrine (10(-8) to 10(-4) mol/L and angiotensin II (10(-10) to 10(-6) mol/L) in isolated, perfused hind limbs of nonpregnant and pregnant (postmating day 20 to 21) normotensive Wistar-Kyoto and spontaneously hypertensive rats. The hind limbs were perfused at 4 ml/min with Krebs-Ringer solution containing indomethacin (10(-5) mol/L to inhibit prostaglandin production and were either infused with N omega-monomethyl-L-arginine (10(-4) mol/L), a specific inhibitor of endothelium-derived relaxing factor synthesis, or 0.9% saline solution (untreated). RESULTS: Baseline perfusion pressure was similar in the nonpregnant and pregnant hind limbs of both strains, and N omega-monomethyl-L-arginine had no effect on perfusion pressure. Norepinephrine induced similar pressor responses in the nonpregnant and pregnant hind limbs of both strains, and N omega-monomethyl-L arginine did not alter these responses. Angiotensin II pressor responses were significantly attenuated in the pregnant rat hind limbs compared with the nonpregnant rat hind limbs. N omega-monomethyl-L-arginine enhanced the angiotensin II responses in the pregnant, but not in the nonpregnant, rat hind limbs. CONCLUSION: The results suggest that rat pregnancy is not associated with generalized refractoriness to all vasoconstrictors and that endothelium-derived relaxing factor plays a role in attenuating vascular reactivity to angiotensin II. PMID- 1415392 TI - The effect of tocolytic agents (indomethacin and terbutaline) on fetal breathing and body movements: a prospective, randomized, double-blind, placebo-controlled clinical trial. AB - OBJECTIVE: The null hypothesis of this study is that maternal administration of indomethacin or terbutaline will not affect fetal breathing and body movements. STUDY DESIGN: Thirty patients with a low-risk pregnancy, gestational age 26 to 32 weeks, and no signs of preterm labor were randomly assigned to receive either terbutaline (5 mg), indomethacin (50 mg), or a placebo. Ultrasonographic evaluation of fetal breathing and body movements was performed for 1 hour before and 1 hour after treatment. The total amount of time of fetal breathing and body movements in each group was subject to statistical analysis that included analysis of variance and covariance and a multiple comparison procedure. RESULTS: Indomethacin increased fetal breathing from 20.8 +/- 13.1 minutes to 42.2 +/- 14.8 minutes (p < 0.01), whereas terbutaline increased fetal breathing movements from 19.8 +/- 9.0 minutes to 35.2 +/- 12.4 minutes (p < 0.01). No significant treatment effect was detected on fetal body movements. CONCLUSION: Between 26 and 32 weeks' gestation, a single dosage of indomethacin or terbutaline increases fetal breathing movements by 103% and 78%, respectively. PMID- 1415393 TI - The effect of maternal intravenous glucose administration on fetal activity. AB - OBJECTIVE: The study was designed to objectively evaluate the effect of maternal intravenous glucose infusion on fetal activity. STUDY DESIGN: Twenty-one volunteers at 30.7 +/- 3.0 weeks' gestation were objectively evaluated for fetal activity with a Doppler monitor before and during an intravenous glucose test. Baseline fetal activity monitoring began 10 minutes before a fasting blood glucose level was obtained. A standard 1-hour intravenous glucose tolerance test was then performed, and fetal activity monitoring was continued for the duration of the test. Twenty-one women at 29.8 +/- 3.0 weeks' gestation volunteered to serve as controls and were continuously monitored for fetal activity. The control patients did not receive intravenous glucose. RESULTS: Linear regression analysis revealed an increase in fetal activity in both groups; however, the increase in the glucose infusion group was significantly greater than in the control group. CONCLUSIONS: Maternal glucose infusion causes short-term stimulation of fetal activity; however, some other factor in the monitoring process also stimulates fetal activity. PMID- 1415394 TI - Fetal blood sampling in human immunodeficiency virus--seropositive women before elective midtrimester termination of pregnancy. AB - OBJECTIVES: To explore the diagnostic potential of fetal blood sampling in the prenatal diagnosis of intrauterine human immunodeficiency virus infection and to investigate the transplacental transfer of human immunodeficiency virus antibody and p24 antigen in the second trimester of pregnancy, we studied serum and amniotic fluid obtained from 13 seropositive women and their fetuses before elective termination of pregnancy. STUDY DESIGN: Enzyme-linked immunosorbent assay, Western blot antibody analyses, and p24 antigen assays were performed on all samples. RESULTS: Human immunodeficiency virus antibody was detected by enzyme-linked immunosorbent assay and Western blot analysis in aliquots of maternal serum, amniotic fluid, and fetal serum from all 13 pregnancies. Each mother-fetus pair had identical antibody banding patterns. In contrast, p24 antigen was found in the maternal serum and amniotic fluid samples from five of 13 women (38%) and in serum from only three of 13 fetuses (23%). CONCLUSIONS: We conclude that fetal blood sampling, if combined with sophisticated serologic analysis, may have the potential to provide the diagnosis of congenital infection with human immunodeficiency virus. The correlation of immunologic, virologic, and molecular biologic methods with subsequent infant outcome and risk of iatrogenic infection of the fetus remains to be determined. PMID- 1415395 TI - Prevalence and prognostic significance of anticardiolipin antibodies in pregnancies complicated by human immunodeficiency virus-1 infection. AB - OBJECTIVES: Anticardiolipin antibodies are estimated to occur in 2.2% of all pregnancies and are associated with adverse outcomes including thrombotic events, fetal wastage, intrauterine growth retardation, and preterm delivery. We studied 32 human immunodeficiency virus-seropositive gravidas (1) to determine the prevalence of anticardiolipin antibodies in pregnant women infected with human immunodeficiency virus-1 and (2) to investigate the association between the presence of anticardiolipin antibodies and pregnancy outcome, disease status, and perinatal transmission of human immunodeficiency virus-1. STUDY DESIGN: Serum samples obtained at the first prenatal visit were analyzed for anticardiolipin immunoglobulin M and immunoglobulin G by enzyme-linked immunosorbent assay. Relevant antepartum, intrapartum, and postpartum data, including maternal CD4+ lymphocyte subsets, human immunodeficiency virus p24 antigen determinations, Venereal Disease Research Laboratory test, hematocrit, platelet counts, and placental pathologic tissue of the anticardiolipin antibody-positive and anticardiolipin antibody-negative groups were compared. RESULTS: Test results for 17 (53%) of patients were positive for anticardiolipin antibody: 4 had only immunoglobulin M, 1 had only immunoglobulin G, and the remaining 12 had both antibodies. The patients in the anticardiolipin antibody-positive group were delivered of infants with a mean gestational age of 39 weeks and mean birth weight of 2983 gm. In the anticardiolipin antibody-negative group 15 deliveries had a mean gestational age of 36.3 weeks and a mean birth weight of 2330 gm. CONCLUSIONS: We conclude that there is a high prevalence of anticardiolipin antibodies in patients who have human immunodeficiency virus, which is not associated with adverse maternal or neonatal outcome, maternal human immunodeficiency virus status, or perinatal transmission of human immunodeficiency virus-1. PMID- 1415396 TI - Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance. AB - OBJECTIVE: The purpose of this study was to determine the prevalence and clinical significance of microbial invasion of the amniotic cavity in patients presenting with cervical dilatation in the midtrimester of pregnancy. STUDY DESIGN: Amniocentesis for microbial studies was performed in women admitted with cervical dilatation > or = 2 cm, intact membranes, and without active labor between 14 and 24 weeks of gestation. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Gram stain was performed on all samples. RESULTS: The prevalence of microbial invasion of the amniotic cavity was 51.5% (17/33). The most common microbial isolates were Ureaplasma urealyticum, Gardnerella vaginalis, Candida albicans, and Fusobacterium sp. All patients with microbial invasion of the amniotic cavity had complications. Patients who underwent cervical cerclage in the presence of a positive amniotic fluid culture had rupture of membranes, clinical chorioamnionitis, or pregnancy loss. On the other hand, the prognosis of patients with a negative amniotic fluid culture was better than that of patients with a positive culture. Of 16 patients with a negative amniotic culture, nine were delivered at > 34 weeks. CONCLUSIONS: (1) Microbial invasion of the amniotic cavity occurs frequently in women presenting with cervical dilatation in the midtrimester; (2) the microbiologic state of the amniotic cavity is an important prognostic factor for pregnancy outcome; (3) amniocentesis to determine the microbiologic characteristics of the amniotic cavity should be considered before a cerclage is placed in women presenting with cervical dilatation in the midtrimester. PMID- 1415398 TI - Obstetric parameters affecting success in a trial of labor: designation of a scoring system. AB - OBJECTIVES: We sought to characterize risk factors in patients undergoing trial of labor after previous cesarean section and to determine whether a subset of patients at high risk of having an unsuccessful trial of labor consequently suffer greater morbidity. STUDY DESIGN: A 13-month chart review analyzed 264 labors with documented transverse lower uterine segment scars. Historic and physical examination variables were recorded, and a scoring system was constructed to evaluate successful vaginal delivery after cesarean. RESULTS: Successful vaginal delivery occurred in 192 patients, resulting in a rate of vaginal birth after cesarean of 72.7%. Four variables significantly lower the rate of vaginal birth after cesarean. Of patients scoring 0 (no variables present), 91.5% were successfully delivered vaginally. Scores of 1, 2, and 3 to 4 were associated with the success of vaginal birth after cesarean in 73.9%, 66.7%, and 46.1% of patients, respectively. A score of 3 to 4 did not increase maternal or fetal morbidity in trial-of-labor patients. CONCLUSION: We constructed a scoring system to evaluate the success of vaginal birth after cesarean. Trial of labor in the subset of patients with the lowest success rate does not increase morbidity. PMID- 1415397 TI - Human immunodeficiency virus infection among inner-city adolescent parturients undergoing routine voluntary screening, July 1987 to March 1991. AB - OBJECTIVE: The objective of our study was to describe the human immunodeficiency virus epidemic among pregnant adolescents undergoing follow-up in a large inner city hospital. STUDY DESIGN: We conducted a case-control study comparing demographic and risk behaviors of seropositive and seronegative adolescents (aged 13 to 20) identified from a population undergoing routine voluntary antibody screening at Grady Memorial Hospital in Atlanta, Georgia, between July 1987 and March 1991. RESULTS: Of 10,794 pregnant adolescents screened, 51 (4.7/1000) were infected with human immunodeficiency virus. More than one fourth of case patients were < or = 17 years old. Significantly more case patients than controls reported a history of crack cocaine use (10 [19.6%] vs 23 [8.2%] p < 0.05). A majority (58.8%) of case patients reported no risk factors for infection, and the remainder (41.2%) were presumably infected by heterosexual contact. Thirty-nine controls (13.8%) had self-identified risk factors for infection. CONCLUSIONS: Pregnant adolescents in our center are at risk for human immunodeficiency virus infection and should be targeted for human immunodeficiency virus education and risk reduction counseling. PMID- 1415399 TI - Early repair of episiotomy dehiscence associated with infection. AB - OBJECTIVE: The purpose of our study was to examine early repair of episiotomy dehiscences in a large urban hospital setting serving a predominantly indigent population. STUDY DESIGN: Since September 1, 1989, we have proceeded with early repair in the immediate postpartum period. The medical records of 34 of 35 patients who underwent early repair were reviewed. RESULTS: Of the 34 patients, 21 (62%) had midline and 13 (38%) had mediolateral episiotomies. Dehiscence was associated with episiotomy infection in 27 (79%) of the 34 patients: 18 (86%) in the midline group and 9 (69%) in the mediolateral group. Repair was accomplished from 3 to 13 days (mean = 6.4) after dehiscence. Successful repairs were accomplished in 32 (94%) of 34 patients. Two (6%) patients with initial third degree episiotomies had a subsequent breakdown of their repairs and were allowed to heal by secondary intention. CONCLUSIONS: Although most dehiscences in our population were associated with infection, early repair in this population is associated with a satisfactory outcome in the vast majority. PMID- 1415400 TI - Transverse uterine incision closure: one versus two layers. AB - OBJECTIVE: Closure of a low transverse cesarean incision with one layer of suture results in less operating time, better hemostasis, and less infectious morbidity than a two-layer closure. STUDY DESIGN: At our institution 906 women were randomized to closure of a low transverse cesarean incision with either one continuous layer of a locking No. 1 chromic suture and a CTX needle (n = 457) or two continuous layers of No. 1 chromic suture with the first layer locked (n = 449). The Student t test, chi 2 test of proportion, and Wilcoxon rank sum test were used to compare groups of patients. RESULTS: A one-layer closure required less operative time, 43.8 versus 47.5 minutes (p = 0.0003). Fewer additional uterine hemostatic sutures were required in 369 women in whom either the one- (n = 179) or the two-layer (n = 190) closure did not achieve hemostasis (p = 0.046). Endometritis was similar in both groups, 83 (22%) in the one-layer group versus 65 (18%) in the two-layer group (p = 0.17). In no outcome assessment was the two layer closure superior to the one-layer closure. CONCLUSION: We recommend a one layer closure when its use is anatomically feasible. PMID- 1415401 TI - Antepartum management of triplet gestations. AB - OBJECTIVE: We evaluated an alternative approach to the management of triplet gestations that did not include home uterine monitoring, prophylactic tocolysis, or routine antepartum hospitalization. STUDY DESIGN: Fifteen patients were managed over a 42-month period by an antepartum protocol that emphasized patient education regarding signs and symptoms of preterm labor, weekly prenatal visits after 24 weeks' gestation with cervical examination, and increased rest in an outpatient setting. Tocolytic therapy was only used for regular uterine contractions when cervical change was documented. RESULTS: Nine of 15 (60%) patients with management in this uniform manner were delivered at > or = 35 weeks' gestation, and six patients (40%) completed 37 weeks of pregnancy. Only five patients (33%) received tocolytic therapy. The mean birth weight was 1957 +/ 488 gm, and only 19 of 45 neonates (42%) were admitted to the intensive care nursery. CONCLUSION: This management scheme was effective in reducing preterm delivery and thereby optimizing perinatal outcome. PMID- 1415402 TI - The development and testing of new instruments for operative vaginal delivery. AB - OBJECTIVE: Little innovation has occurred in recent years in the instruments available for operative vaginal delivery. The purpose of this study is to develop a technique to test the utility of an investigational device, the obstetric bonnet, and measure the forces it places on the fetal head. STUDY DESIGN: We constructed a model of the fetal head capable of measuring both compression and vacuum created by an applied device. A total of 18 devices were tested to a maximum traction of 60 pounds. RESULTS: A significant linear relationship exists between the traction applied and the compression (R2 = 0.42, p = 0.0004) and vacuum (R2 = 0.85, p = 0.0001) created. Compression and vacuum recorded at maximum recommended traction were 1.1 lb/sq in and 31 cm Hg, respectively. CONCLUSION: These findings explain the mechanics of this interesting device, and demonstrate forces that compare favorably with those known to occur with forceps or vacuum extraction. PMID- 1415403 TI - Effect of angular traction on the performance of modern vacuum extractors. AB - OBJECTIVE: Our objective was to describe the effect of off-axis traction on the performance of modern vacuum extractors. STUDY DESIGN: Eight vacuum extractors were examined in the laboratory with a force indicator and fetal cephalic model. Devices evaluated included the 6 cm Malmstrom, Mity-Vac, M-Type, O'Neil, Posterior, Silc, Tender-Touch, and silicone elastomer. Maximal tractive force (pop-off) was measured for each device at 10-degrees increments from the vertical. RESULTS: Multivariate regression analysis described the best model as follows: Maximal tractive force = Constant + Angle + Vacuum (p < 0.05). The partial regression coefficients for angle were negative in all devices except the Posterior cup. At increasing angles of off-axis traction, maximal tractive force decreased in the following order: Silc, silicone elastomer, Tender-Touch, M-Type, Mity-Vac, O'Neill, Malmstrom, and Posterior. CONCLUSIONS: Application of oblique traction resulted in a linear decline in maximal tractive force. An understanding of in vitro performance may allow tailoring of cup selection to the clinical situation. PMID- 1415404 TI - How frequently should the amniotic fluid index be repeated? AB - OBJECTIVE: Our objective was to determine the most appropriate interval for assessing amniotic fluid volume with amniotic fluid index. STUDY DESIGN: In a retrospective analysis amniotic fluid indexes performed every 3 to 4 days in antepartum testing patients were compared with their follow-up values. Of 10,742 amniotic fluid indexes there were 7393 with follow-up values within 4 days. The results were stratified by current amniotic fluid index, gestational age, and concurrent nonstress test results. The groups were compared with chi 2 analysis. RESULTS: Patients with normal amniotic fluid index (> or = 8 cm) had a 0.54% chance of oligohydramnios developing in the next 4 days. Those patients with low normal amniotic fluid indexes (5 to 8 cm) had a 5% chance of oligohydramnios developing within the next 4 days, and patients with low amniotic fluid indexes (< or = 5 cm) had a 59% chance of persistent oligohydramnios 4 days after the index examination. Subdividing by gestational age demonstrated that patients > or = 41 weeks' gestation had a 2.6% chance of oligohydramnios developing within 4 days if current amniotic fluid index was between 8 and 15 cm. Results of concurrent fetal heart rate findings did not appear to change the risk for development of oligohydramnios. CONCLUSION: In patients < 41 weeks' gestation with normal amniotic fluid indexes, a repeat amniotic fluid index is not necessary for 7 days. PMID- 1415405 TI - Amnioinfusion does not affect the length of labor. AB - OBJECTIVE: Our objective was to determine whether amnioinfusion prolongs or shortens the length of labor in patients who have an accepted indication for amnioinfusion. STUDY DESIGN: We performed a retrospective post hoc analysis of the length of labor of 437 patients who were enrolled in three prospective, randomized, controlled studies of amnioinfusion. RESULTS: The length of labor was not significantly different for patients who received amnioinfusion compared with those who did not receive amnioinfusion (control group). Among the subgroup with vaginal delivery, the duration of labor after amnioinfusion did not differ from the duration of labor among the controls. The length of labor (mean +/- SD, in hours) for the amnioinfusion group was 9.3 +/- 6.3 versus 10.6 +/- 6.9 for the control groups (p not significant). Among the subgroup that required cesarean delivery, the duration of labor after amnioinfusion did not differ from the duration of labor among the controls. The length of labor (mean +/- SD, in hours) in patients requiring cesarean delivery in the amnioinfusion group was 11.1 +/- 6.3 versus 13.0 +/- 7.5 for the control group (p not significant). CONCLUSION: Amnioinfusion does not prolong or shorten the length of labor among patients who have an accepted indication for the treatment. PMID- 1415406 TI - Position of the vibroacoustic stimulator does not affect fetal response. AB - OBJECTIVE: This study was designed to compare the fetal response to the vibroacoustic stimulation test when applied alternately over the fetal vertex or breech. STUDY DESIGN: Two hundred five patients with a nonreactive nonstress test after 10 minutes were prospectively randomized to receive the vibroacoustic stimulation test over the fetal vertex (n = 115) or the fetal breech (n = 90). Fetal heart rate reactivity was evaluated. Two patient subsets were evaluated for fetal movement (n = 37) and the fetal startle response (n = 20) after the vibroacoustic stimulation test. RESULTS: Virtually identical fetal heart rate responses and increases in fetal movement were observed after vibroacoustic stimulation over the fetal vertex or breech. The fetal startle response was uniformly observed in both groups. CONCLUSION: Vibroacoustic stimulation over the fetal breech elicits an identical short-term fetal response compared with stimulation over the fetal vertex, potentially reducing the intensity of sound exposure at the fetal ear. PMID- 1415407 TI - Fetal heart rate accelerations, fetal movement, and fetal behavior patterns in twin gestations. AB - OBJECTIVE: Previous studies have shown that twins, when monitored simultaneously, show a remarkably high incidence of coincident fetal heart rate accelerations (about 58%). The current study examines synchrony of behavior patterns in twins. STUDY DESIGN: We examined 37 fetal monitor strips from 15 sets of twins with simultaneous fetal heart rate and fetal movement recorded by means of Doppler techniques (Toitu MT-430 fetal actocardiograph). The strips were analyzed for coincidence of fetal heart rate accelerations and fetal movement episodes and then conceptually for synchrony of fetal behavior patterns on the basis of descriptions of behavioral states by Prechtl. RESULTS: Thirty-six percent of fetal heart rate accelerations were found to be simultaneous. Forty-three percent of movement epochs were considered simultaneous. We found that twins exhibited synchronous behavior patterns (basically sleep or awake state) 94.7% of the time. CONCLUSION: Twin-twin interactions are more consistently related than suspected when observation is limited to heart rate alone, and the synchrony and role of fetal behavior states must be considered when twin interactions and behavior are studied. PMID- 1415408 TI - Birth weight threshold for postponing preterm birth. AB - OBJECTIVE: The study was designed to determine the birth weight threshold at which obstetric efforts intended to delay delivery might potentially improve rates of neonatal morbidity and mortality among pregnancies delivered after spontaneous preterm labor or rupture of the membranes. STUDY DESIGN: We studied 1147 singleton infants with birth weights between 1000 and 2499 gm and whose only complication was spontaneous preterm labor or preterm rupture of the membranes. The Mantel-Haenszel chi 2 statistic was used to evaluate trends for neonatal mortality and several indexes of morbidity. RESULTS: The birth weight threshold for neonatal mortality was 1600 gm (p < 0.001). For neonatal morbidity the threshold was between 1600 and 1900 gm (p < 0.008). CONCLUSION: Aggressive obstetric attempts to prevent preterm birth for infants whose weights exceed 1900 gm offers few apparent potential benefits. PMID- 1415409 TI - Laparoscopic electrosurgical oophorectomy: risk of using "blanching" as the end point. PMID- 1415410 TI - Subchorionic hematoma and autoantibodies: is there a relation? PMID- 1415411 TI - Is the glucose challenge test really unnecessary? PMID- 1415412 TI - Composite assessment of gestational age. PMID- 1415413 TI - Anticardiolipin tests in healthy pregnant women. PMID- 1415414 TI - Oral magnesium chloride for the prevention of recurrent preterm labor. PMID- 1415415 TI - The dosing of subcutaneous terbutaline pump tocolytic therapy is critical. PMID- 1415416 TI - Milrinone use in the pregnant ewe. PMID- 1415417 TI - The natural interleukin-1 receptor antagonist in term and preterm parturition. AB - OBJECTIVE: Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The interleukin-1 receptor antagonist is a new member of the interleukin-1 gene family that inhibits the biologic effects of interleukin-1 by blocking its receptors. Reduction of interleukin-1 induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of interleukin-1 receptor antagonist on interleukin 1-induced prostaglandin biosynthesis by human amnion and chorion. STUDY DESIGN: Amniotic fluid was obtained from women in the midtrimester of pregnancy (n = 20), at term pregnancy (with and without labor, n = 69), and in preterm labor (n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of interleukin-1 receptor antagonist on interleukin-1 induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with interleukin-1 receptor antagonist and interleukin-1 alpha or interleukin-1 beta for 16 hours. Prostaglandin E2 released into the media was assayed by immunoassay. RESULTS: (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of interleukin-1 alpha and interleukin-1 beta in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) interleukin-1 receptor antagonist reduced interleukin-1 beta-induced prostaglandin E2 production by amnion and chorion in a dose-dependent manner; (5) interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. CONCLUSIONS: (1) Interleukin-1 receptor antagonist is a physiologic component of amniotic fluid; (2) the release of interleukin-1 alpha and interleukin-1 beta into the amniotic fluid in women with preterm labor is not associated with an increase in interleukin-1 receptor antagonist levels in amniotic fluid; (3) interleukin-1 receptor antagonist reduces interleukin-1 induced prostaglandin production by amnion and chorion; (4) exogenous anticytokine agents may be of value in the treatment of preterm labor. PMID- 1415418 TI - Neonatal periventricular-intraventricular hemorrhage after maternal beta sympathomimetic tocolysis. The March of Dimes Multicenter Study Group. AB - OBJECTIVE: Our objective was to determine if the rate of periventricular intraventricular hemorrhage is increased in the offspring of women who received a beta-sympathomimetic agent as part of the management of preterm labor. STUDY DESIGN: This retrospective study consists of 2827 women who were delivered of a singleton, live infant free of congenital neurologic anomalies between 25 and 36 completed weeks of gestation during a multicenter preterm birth prevention trial. The data were analyzed, adjusting for type of tocolytic agent, race, infant sex, gestational age, birth weight, health care center, route of delivery, indication for delivery, intrapartum fetal distress, respiratory distress syndrome, and neonatal sepsis. RESULTS: The overall incidence of periventricular intraventricular hemorrhage in this population was 5.6%. In a univariate analysis in which no adjustment was made for potentially confounding variables, beta sympathomimetic tocolysis was found to be associated with nearly a fourfold increase in the incidence of periventricular-intraventricular hemorrhage when compared with the use of either magnesium sulfate or no tocolytic agent. The results of a multivariate regression analysis revealed that beta-sympathomimetic agents were associated with a statistically significant increase in the overall incidence of periventricular-intraventricular hemorrhage (odds ratio 2.47, 95% confidence interval 1.34 to 4.56, p = 0.004) and a similar, but not significant, increase in the incidence of grades 3 and 4 periventricular-intraventricular hemorrhage (odds ratio 2.50, 95% confidence interval 0.96 to 6.48, p = 0.06). CONCLUSION: beta-Sympathomimetic tocolytic therapy may be associated with a more than twofold increase in the incidence of neonatal periventricular intraventricular hemorrhage. PMID- 1415419 TI - A randomized prospective comparison of nifedipine and bed rest versus bed rest alone in the management of preeclampsia remote from term. AB - OBJECTIVE: The objective of our study was to test the hypothesis that treatment with nifedipine for mild preeclampsia remote from term reduces the number of days of maternal hospitalization and improves pregnancy outcome. STUDY DESIGN: A total of 200 patients at 26 to 36 weeks' gestation were randomly allocated to treatment with either bed rest alone (n = 100) or bed rest in combination with nifedipine (n = 100). RESULTS: Patients receiving nifedipine had significantly lower systolic (p < 0.0001) and diastolic (p < 0.0001) blood pressures during therapy. Severe hypertension as an indication for delivery was significantly (p < 0.05) more frequent in the bed-rest-alone group. The two study groups had similar average days of maternal hospitalization (12.6 +/- 7.9 vs 12.3 +/- 10.3) and pregnancy prolongation (22.3 +/- 13.5 vs 22.5 +/- 15.7). There were no differences between groups with respect to birth weight, incidences of small-for gestational-age infants and preterm birth, number of days spent in special care unit, or cord blood gas measurement. CONCLUSION: Nifedipine therapy for preeclampsia reduces maternal blood pressure but does not reduce number of days of maternal hospitalization or improve perinatal outcome. PMID- 1415420 TI - Magnesium pyrrolidone carboxylate infusion reduces angiotensin II pressor response in pregnant women at risk for hypertension. AB - OBJECTIVE: Our objective was to investigate the possible restoring action of magnesium on vascular sensitivity to angiotensin II in pregnancy. STUDY DESIGN: We studied intraplatelet free calcium and the pressor response to angiotensin II in 10 primigravid women (28 to 32 weeks' gestation) at risk for pregnancy induced hypertension on the basis of altered uteroplacental blood velocity waveforms at 20 weeks' gestation, before and after the infusion of 1 gm of magnesium pyrrolidone carboxylate. After the effective pressor dose was achieved or a maximum of 32 ng/kg per minute was reached, we infused 1 gm magnesium pyrrolidone carboxylate and repeated the test. Intraplatelet free calcium was measured by means of fluorescent probes at the beginning and the end of both tests. RESULTS: Six women were classified as refractory to angiotensin II and four as sensitive (effective pressor dose < 10 ng/kg per minute). After magnesium pyrrolidone carboxylate infusion, the four sensitive women became refractory and the effective pressor dose was significantly enhanced to 32 in all six refractory women. Intracellular free calcium increased significantly during the first angiotensin II infusion, whereas after magnesium pyrrolidone carboxylate administration it did not change significantly. CONCLUSIONS: Magnesium pyrrolidone carboxylate enhances the vascular refractoriness and intracellular free calcium mediates the pressor response to angiotensin II in pregnancy. PMID- 1415421 TI - Second-trimester echogenic bowel and chromosomal abnormalities. AB - OBJECTIVE: Our objective was to examine the outcomes of pregnancies in which echogenic bowel was detected in the second trimester. STUDY DESIGN: Twenty-two cases with a prospective diagnosis of echogenic bowel were reviewed. Karyotypic studies were performed in 19 cases, and 17 families had deoxyribonucleic acid based risk assessment for cystic fibrosis. The echogenicity of the bowel was retrospectively reviewed and graded as mild or bright. RESULTS: Five cases of trisomy 21 and one case of trisomy 18 were detected; four of these had other ultrasonographic abnormalities. Twenty-seven percent of fetuses with echogenic bowel were aneuploid. Risk was greatest for cases with brightly echogenic bowel. No cystic fibrosis mutations were detected. The diagnosis of echogenic bowel was reproducible. CONCLUSION: Brightly echogenic bowel in the second trimester was found to be associated with a significant risk of fetal aneuploidy. PMID- 1415422 TI - Circulating lymphocyte subsets in second- and third-trimester fetuses: comparison with newborns and adults. AB - OBJECTIVES: Our objective was to compare the relative sizes of circulating lymphocyte subsets in fetuses, newborns, and adults. STUDY DESIGN: Two-color flow cytometric analysis of lymphocyte cell surface markers was performed on blood from 64 fetuses, 22 newborns, and 67 normal adults. RESULTS: All three groups had similar percentages of CD3+ total T cells, CD4+ helper T cells, CD8+ cytotoxic/suppressor T cells, and CD20+ B cells. Compared with adults, fetuses and newborns had markedly reduced percentages of CD57+ natural killer T cells and consistently increased percentages of CD5+CD20+ B cells. Most fetal and cord T and B lymphocytes expressed the activation marker CD38. CONCLUSIONS: Similarities and age-dependent differences exist among fetal, newborn, and adult circulating lymphocyte subsets. Lymphocyte marker analysis may prove useful in the detection of fetal infection and other complications of gestation. PMID- 1415423 TI - The effect of presentation and mode of delivery on neonatal outcome in the second twin. AB - OBJECTIVE: The purpose of this study was to determine if cesarean delivery of the nonvertex second twin improved neonatal outcome. STUDY DESIGN: We examined the maternal and neonatal records from 457 sets of twins delivered from 1985 to 1990. We compared 1- and 5-minute Apgar scores, umbilical artery and vein blood pH values, duration of neonatal hospitalization, the incidence and length of ventilation, intraventricular hemorrhage, birth trauma, and mortality rate between vertex and nonvertex second twins delivered either vaginally or by cesarean section. RESULTS: The presentation and mode of delivery of the second twin was not associated with a significant difference in any of the outcome variables except for the 1-minute Apgar score, which was lower in the nonvertex group delivered vaginally. CONCLUSION: Our data do not support routine cesarean delivery for twins of any birth weight when the second twin is nonvertex. PMID- 1415424 TI - Do abnormal Starling forces cause fetal hydrops in red blood cell alloimmunization? AB - OBJECTIVE: The purpose of the current investigation was to ascertain whether derangements in umbilical venous pressure and plasma colloid osmotic pressure are involved in the pathophysiologic condition of immune hydrops fetalis. STUDY DESIGN: Umbilical venous pressure (corrected for ambient amniotic fluid pressure) and colloid osmotic pressure were measured during intravascular transfusion. Fetal hydrops was defined as the presence of ascites by ultrasonography. The Mann Whitney test was used for comparison of groups; a value of p < 0.05 was considered statistically significant. RESULTS: Fifteen hydropic fetuses were matched for gestational age with 15 nonhydropic fetuses also undergoing intrauterine transfusion for anemia. On comparison with their nonhydropic counterparts, hydropic fetuses had a statistically lower colloid osmotic pressure. Umbilical venous pressure was higher and the colloid osmotic pressure- umbilical venous pressure gradient was lower in association with fetal hydrops although these differences did not achieve statistical significance. CONCLUSION: Mild abnormalities of intravascular Starling forces may play a role in the formation of hydrops in anemic fetuses. PMID- 1415425 TI - Longitudinal changes in basal hepatic glucose production and suppression during insulin infusion in normal pregnant women. AB - OBJECTIVE: The purpose of this study was to evaluate basal endogenous glucose production and suppression during insulin infusion in normal pregnant women. STUDY DESIGN: This prospective, longitudinal study was conducted at the Medical Center Hospital of Vermont. Six healthy women were evaluated before conception and at 12 to 14 and 34 to 36 weeks' gestation. Body composition was estimated by hydrodensitometry. Basal endogenous glucose production was estimated with a primed constant infusion of 6-6 2H2 glucose, and suppression of endogenous glucose production was estimated with insulin infusion during a hyperinsulinemic euglycemic clamp. RESULTS: There was a significant (p = 0.02) 65% increase in fasting insulin concentration by late gestation. Moreover, there was a significant 30% (p = 0.0005) increase in basal endogenous glucose production (mg/min) with advancing gestation, which remained significant (p = 0.05) when corrected for fat-free mass. During insulin infusion endogenous glucose production was almost completely suppressed (i.e., > 90%) throughout gestation. CONCLUSIONS: There is a significant increase in basal endogenous glucose production at 34 to 36 weeks' gestation in spite of a significant increase in fasting insulin concentration. However, endogenous glucose production remains sensitive to insulin infusion throughout gestation. PMID- 1415426 TI - Tumor necrosis factor-alpha in midtrimester amniotic fluid is associated with impaired intrauterine fetal growth. AB - OBJECTIVE: To investigate whether abnormal immune system activation is involved in the pathogenesis of some instances of impaired fetal growth, we compared tumor necrosis factor-alpha levels in midtrimester amniotic fluid samples obtained from appropriate-for-gestational-age and small-for-gestational-age pregnancies. STUDY DESIGN: In a case-control study with the sensitive and specific WEHI cell assay, bioactive tumor necrosis factor-alpha levels in amniotic fluid samples from 24 gestations resulting in small-for-gestational-age infants were compared with levels in 35 samples obtained from gestations resulting in the birth of a term, appropriate-for-gestational-age infant. The two groups were not significantly different with regard to indication for amniocentesis, maternal age, race, smoking history, parity, or other factors. RESULTS: Elevated amniotic fluid tumor necrosis factor-alpha activity was associated with small-for-gestational-age birth, p = 0.028. With a threshold of 10 pg/ml, elevated amniotic fluid tumor necrosis factor-alpha had a sensitivity of 48% for the detection of small-for gestational-age birth, with a specificity of 83%. CONCLUSION: Elevated tumor necrosis factor-alpha in midtrimester amniotic fluid is associated with impaired intrauterine fetal growth. Abnormal immune system activation, as manifested by increased amniotic fluid tumor necrosis factor-alpha activity, may mediate impaired fetal growth in some cases. PMID- 1415427 TI - Low-dose aspirin inhibits lipid peroxides and thromboxane but not prostacyclin in pregnant women. AB - OBJECTIVE: Preeclampsia is associated with an imbalance of increased thromboxane and decreased prostacyclin and an abnormal increase of lipid peroxides. Lipid peroxides are toxic compounds that damage cells and inhibit prostacyclin synthesis. Low-dose aspirin therapy reduces the incidence of preeclampsia, presumably by selective inhibition of thromboxane to restore a balance between thromboxane and prostacyclin. However, the effectiveness of low-dose aspirin might also relate to inhibition of lipid peroxides. STUDY DESIGN: To test this hypothesis, 10 women at risk of preeclampsia were placed on low-dose aspirin therapy (81 mg/day) between 9 and 34 weeks of gestation. Plasma samples were collected before and after 3 to 4 days and 3 to 4 weeks of aspirin therapy. Samples were analyzed for thromboxane and prostacyclin by radioimmunoassay of their stable metabolites, thromboxane B2 and 6-keto-prostaglandin F1 alpha, and for lipid peroxides by hydrogen peroxide equivalents. RESULTS: Low-dose aspirin significantly decreased (p < 0.05) both lipid peroxides (130 +/- 18 vs 92 +/- 11 and 68 +/- 9 nmol/ml, mean +/- SE) and thromboxane (502 +/- 67 vs 138 +/- 67 and 8 +/- 5 pg/ml), but it did not affect prostacyclin (55 +/- 10 vs 41 +/- 8 and 40 +/- 11 pg/ml, p > 0.1). CONCLUSION: Low-dose aspirin selectively inhibits both lipid peroxides and thromboxane without affecting prostacyclin. Inhibition of both lipid peroxides and thromboxane by low-dose aspirin reveals a new mechanism of action and may account for its effectiveness in the prevention of preeclampsia. PMID- 1415428 TI - Cerebral imaging in eclampsia: magnetic resonance imaging versus computed tomography. AB - OBJECTIVES: Our objectives were to study the cerebral pathophysiology of eclampsia with the noninvasive technique of magnetic resonance imaging to compare the ability of magnetic resonance imaging to detect cerebral abnormalities in eclampsia with that of computed tomography. STUDY DESIGN: Twenty-four patients with eclampsia received both magnetic resonance imaging and computed tomographic scanning. RESULTS: Forty-six percent of the magnetic resonance imaging was abnormal and 33% of the computed tomography was abnormal. This higher incidence of abnormal magnetic resonance imaging scans was present in spite of the fact that they were obtained significantly longer after the patient's seizure activity. The most common abnormalities were cortisol, subcortical, and white matter edema. CONCLUSION: Magnetic resonance imaging and computed tomographic scan abnormalities in eclampsia are usually similar. Cerebral imaging is not necessary in patients with uncomplicated eclampsia. PMID- 1415429 TI - Nifedipine treatment in preeclampsia reverts the increased erythrocyte aggregation to normal. AB - OBJECTIVES: Our objectives were to assess erythrocyte aggregation in hypertensive pregnancy and to evaluate the effect of the antihypertensive treatment on it. STUDY DESIGN: The mean entity of erythrocyte aggregation was determined by an automatic aggregometer in 57 pregnant women: 20 normotensive, seven chronically hypertensive, 10 chronically hypertensive with superimposed preeclampsia, and 20 with preeclampsia. Ten of the latter were subsequently treated by 40 mg/day oral nifedipine; the other 10 by 400 mg/day oral labetalol, to keep diastolic blood pressure < 90 mm Hg. Also, patients with superimposed preeclampsia were treated with 40 mg/day oral nifedipine. RESULTS: Erythrocyte aggregation was increased in all the hypertensive pregnant patients compared with the normotensive pregnant controls, regardless of both the onset (chronic or pregnancy-induced) of hypertension and the status of plasma macromolecules. Antihypertensive treatment with labetalol significantly reduced the aggregability of erythrocytes, whereas treatment with nifedipine reverted it to normal. CONCLUSIONS: Increased erythrocyte aggregation may be due to either conformational changes of the membrane occurring during hypertension or a redistribution of the ionic charges on the two surfaces of the membrane. The effect of nifedipine by restoring the ionic charges may be due to this latter event. PMID- 1415430 TI - Placental lipid peroxides and thromboxane are increased and prostacyclin is decreased in women with preeclampsia. AB - OBJECTIVE: There is an imbalance of increased thromboxane and decreased prostacyclin in placentas of women with preeclampsia, but this may not be the only imbalance. There is also an abnormal increase in serum lipid peroxides in preeclamptic women. Lipid peroxides are toxic compounds that damage cells and inhibit prostacyclin synthesis. The following study examined lipid peroxides to determine if they were also increased in placentas of preeclamptic women. STUDY DESIGN: Placental tissue for nine normal and eight preeclamptic women were frozen in liquid nitrogen immediately after delivery. Frozen tissue samples (1 gm) were homogenized and analyzed for lipid peroxides by malondialdehyde and hydrogen peroxide equivalents and for thromboxane and prostacyclin by radioimmunoassay of their stable metabolites, thromboxane B2 and 6-keto prostaglandin F1 alpha. RESULTS: Lipid peroxides were significantly higher in preeclamptic placentas than in normal placentas by both analytic methods (49 +/- 5 vs 31 +/- 1 nmol/gm for malondialdehyde and 5.3 +/- 0.3 vs. 3.2 +/- 0.3 mumol/gm for hydrogen peroxide equivalent; mean +/- SE; p < 0.01, respectively). Thromboxane was significantly higher and prostacyclin significantly lower in preeclamptic placentas than in normal placentas (213 +/- 23 vs 158 +/- 14 ng/gm for thromboxane and 24 +/- 3 vs 53 +/- 7 ng/gm for prostacyclin, p < 0.05). The thromboxane/prostacyclin and lipid peroxides/prostacyclin ratios were threefold higher in preeclamptic placentas than in normal placentas. CONCLUSION: Placental levels of both lipid peroxides and thromboxane are increased and prostacyclin decreased in preeclampsia. We speculate that abnormally increased levels of lipid peroxides in preeclamptic placentas may be a cause of decreased prostacyclin. PMID- 1415431 TI - Adult respiratory distress syndrome in pregnancy. AB - OBJECTIVE: Our objective was to determine the causes of adult respiratory distress syndrome in pregnancy, the treatment required, and maternal and perinatal outcomes. STUDY DESIGN: We examined a case series of 16 patients with adult respiratory distress syndrome initially treated in an obstetric intensive care unit. Criteria for the diagnosis were respiratory distress requiring mechanical ventilation and a lung injury score > 2.5. RESULTS: The incidence of adult respiratory distress syndrome in pregnancy was 1 per 2893 deliveries, occurring primarily in the third trimester. The causes were infection (n = 8), preeclampsia/eclampsia (n = 4), hemorrhage (n = 2), thrombotic thrombocytopenic purpura (n = 1), and smoke inhalation (n = 1). Most patients (69%) were delivered before or soon after admission to our hospital. Multiple organ failure developed in 12 patients (75%). Complications of mechanical ventilation occurred in 81% of cases. Other complications of intensive care unit support were endocarditis, superior vena cava thrombosis, line sepsis, and bacteremia. Maternal mortality was 44%; perinatal mortality was 20%. CONCLUSIONS: Adult respiratory distress syndrome in pregnancy is associated with a maternal mortality similar to that of studies in the nonpregnant patient. The main causes in pregnancy are hemorrhage, infection, and toxemia. All maternal deaths occurred in patients with multiorgan failure. PMID- 1415432 TI - Perinatal outcome in pregnancy complicated by massive obesity. AB - OBJECTIVE: Our objective was to determine the impact of massive obesity during pregnancy, defined as maternal weight > 300 pounds, on perinatal outcome. STUDY DESIGN: A case-controlled study was conducted. Between Jan. 1, 1986, and Dec. 31, 1990, 111 pregnant women weighing > 300 pounds who were delivered at Long Beach Memorial Women's Hospital were identified with a perinatal data base search. A control group matched for maternal age and parity was selected, and perinatal variables were compared between groups. To control for potential confounding medical complications, massively obese patients with diabetes and/or chronic hypertension antedating the index pregnancy were excluded from the obese group, and the data were reanalyzed. The Student t test chi 2, and Fisher's exact statistical analysis were used where appropriate. RESULTS: Massively obese pregnant women are significantly more likely to have a multitude of adverse perinatal outcomes, including primary cesarean section (32.4% vs 14.3%, p = 0.002), macrosomia (30.2% vs 11.6%, p = 0.0001), intrauterine growth retardation (8.1% vs 0.9%, p = 0.03), and neonatal admission to the intensive care unit (15.6% vs 4.5%, p = 0.01). They also are significantly more likely to have chronic hypertension (27.0% vs 0.9%, p < 0.0001) and insulin-dependent diabetes mellitus (19.8% vs 2.7%, p = 0.0001). However, when those massively obese pregnant women with diabetes and/or hypertension antedating pregnancy are excluded from analysis, no statistically significant differences in perinatal outcome persisted. CONCLUSION: Massively obese pregnant women are at high risk for adverse perinatal outcome; however, this risk appears to be related to medical complications of obesity. PMID- 1415433 TI - Severity of asthma and perinatal outcome. AB - OBJECTIVE: Our objective was to determine the impact of asthma and its severity, as determined by medication requirements, on perinatal outcome. STUDY DESIGN: A case-controlled study was conducted. Among 30,940 live births at Long Beach Memorial Medical Center Women's Hospital, 183 deliveries occurred between Jan. 1, 1985, and Dec. 31, 1990, that were coded for the diagnosis of asthma. Eighty-one that required the chronic use of medications to control their disease were identified. Thirty-one patients were steroid dependent and 50 were non-steroid medication dependent. A control group was randomly selected (excluding maternal transports), and selected perinatal variables were compared between groups. RESULTS: When compared with controls, steroid-dependent asthmatics were at significantly increased risk for gestational (1.5% vs 12.9%) and insulin requiring diabetes (0% vs 9.7%). Preterm delivery and preterm premature ruptured membranes occurred significantly more often in both asthmatic groups. Overall cesarean section rate was significantly increased in the non-steroid-medication dependent asthmatic group when compared with controls (56.0% vs 30.0%). Delivery by primary cesarean section was significantly more common in the steroid dependent group (38.7% vs 19.2%), and a strong trend was noted among the non steroid-medication-dependent patients (34.0% vs 19.2%). Cesarean delivery for fetal distress was also more common in these two asthmatic groups. Neonates born to both groups of asthmatic pregnant women were significantly more likely to be of birth weight < 2500 gm but did not have an increased frequency of intrauterine growth restriction. No significant differences in low 5-minute Apgar scores were found; however, neonates born to both steroid-dependent and non-steroid medication-dependent asthmatics were significantly more likely to be admitted to the neonatal intensive care unit (39.0% and 22.0% vs 7.7%). Preterm delivery and low birth weight were complications observed significantly more often in the steroid-dependent asthma group when compared with the non-steroid-medication dependent group (54.8% vs 14.0% and 45.2% vs 14.0%). CONCLUSIONS: Perinatal outcome is compromised in the pregnancy complicated by chronic medication dependent asthma. The extent is variable and is associated with disease severity, as measured by medication requirements. PMID- 1415434 TI - Pregnancy loss and thrombosis with protein C deficiency. AB - OBJECTIVES: Protein C inhibits coagulation and promotes fibrinolysis. This study investigates the association between protein C deficiency and pregnancy loss, thrombosis in pregnancy, and thrombosis with oral contraception. STUDY DESIGN: Fifteen protein C--deficient patients and 37 controls from a single kindred were studied. An obstetric history was obtained by telephone. Data were analyzed by logistic regression, Fisher's exact test, and Student t test. RESULTS: Protein C- deficient women experienced a 33% pregnancy loss versus 19% in the controls (not significant). Thromboembolism during pregnancy in protein C--deficient women was 33% (45% in those not receiving prophylactic anticoagulation) versus 5% in controls (odds ratio 7.37, p = 0.026). Five of 12 protein C--deficient women using oral contraception developed thrombosis versus 0 of 33 controls. The risk of thrombosis for protein C--deficient women using oral contraception is increased (p < 0.001). CONCLUSIONS: Perinatal outcome is not statistically different with protein C deficiency. Protein C deficiency increases the risk of thrombosis during pregnancy and with oral contraception. Prophylactic heparin is suggested during pregnancy for protein C--deficient women with personal or family histories of thrombosis. Oral contraception is not advised. PMID- 1415435 TI - The prevalence of sexual assault: a survey of 2404 puerperal women. AB - OBJECTIVE: The purpose of this investigation was to determine the prevalence of sexual assault, to characterize pregnancy complications, and to report pregnancy outcomes of assault victims. STUDY DESIGN: Puerperal women (n = 2404) were interviewed regarding a history of forced sexual contact. Obstetric, medical, and forensic records were reviewed. Statistical analysis was performed by Student t test, chi 2 test, or Fisher's exact test. RESULTS: The lifetime prevalence of sexual assault in this obstetric population was 5% (n = 120). Rape victims had a higher incidence of sexually transmitted diseases (9% vs 4%, p < 0.01), urinary tract infections or vaginitis (32% vs 21%, p = 0.02), drug use (9% vs 2%, p < 0.001), and multiple hospitalizations during the index pregnancy (15% vs 8%, p < 0.01). There was no difference between victims and nonvictims in neonatal outcome as reflected by umbilical artery blood pH, gestational age, or birth weight. CONCLUSIONS: A history of sexual assault is common in an urban indigent obstetric population. These women have more frequent pregnancy complications but achieve normal pregnancy outcomes. PMID- 1415436 TI - Maternal characteristics, neonatal outcome, and the time of diagnosis of gestational diabetes. AB - OBJECTIVE: A study was undertaken to evaluate the yield of early, routine screening for gestational diabetes and to determine whether maternal characteristics and neonatal outcome differ according to the time of diagnosis. STUDY DESIGN: A total of 2776 women were screened before 24 weeks of gestation, and each was delivered of a singleton infant on the clinic service of Mount Sinai Hospital in New York City between January 1986 and January 1991. RESULTS: An abnormal glucose tolerance test was diagnosed in 102 women < 24 weeks and in 252 patients at > or = 24 weeks of gestation. Logistic regression analysis showed that the group diagnosed early was significantly older and more likely to have hypertensive disorders and low maternal weight gain and to require insulin treatment, compared with the group diagnosed late. No significant differences were evident in neonatal outcome. CONCLUSIONS: These data indicate that a sizable proportion of patients with gestational diabetes can be diagnosed early in pregnancy. The differences in maternal characteristics and insulin requirements between the early- and late-diagnosis groups also suggest heterogeneity of gestational diabetes or the possibility of preexisting impaired glucose intolerance in the early-diagnosis group. PMID- 1415437 TI - Transverse cerebellar diameter measurements in twin pregnancies and the effect of intrauterine growth retardation. AB - OBJECTIVES: Transverse cerebellar diameter measurements have been established for singleton but not twin pregnancies. In singleton pregnancies controversy exists on whether cerebellar growth is affected by intrauterine growth retardation. We undertook this retrospective study in twin pregnancies to establish a nomogram for the transverse cerebellar diameter in twins and to assess the effect of growth retardation on this measurement. STUDY DESIGN: A retrospective review was performed on 171 patients with twin pregnancies with reliable dating from 15 to 36 weeks' gestation who had been referred to our antenatal evaluation unit for routine ultrasonographic examination. Of the 342 fetuses, 322 were available for analysis and establishment of a nomogram for the transverse cerebellar diameter. Twenty-four twin, growth-retarded fetuses were analyzed separately. RESULTS: The transverse cerebellar diameter increased linearly with gestational age (r = 0.94, p < 0.001). Fifteen (63%) of the growth-retarded fetuses had a transverse cerebellar diameter of < or = 5th percentile for gestational age. CONCLUSION: We suggest that intrauterine growth retardation may affect cerebellar growth in twins. PMID- 1415438 TI - Amniotic fluid volume assessment: comparison of ultrasonographic estimates versus direct measurements with a dye-dilution technique in human pregnancy. AB - OBJECTIVE: The purpose of our study was to compare the accuracy of clinical ultrasonographic techniques of amniotic fluid volume assessment with a dye dilution technique. STUDY DESIGN: We compared amniotic fluid volume as measured by ultrasonographic techniques with a dye-dilution method in 50 women undergoing amniocentesis during the third trimester. Thirteen separate ultrasonographic techniques, including the amniotic fluid index, were evaluated with regression analysis. RESULTS: Amniotic fluid volumes as determined by dye-dilution ranged between 129 and 4444 ml. The amniotic fluid index overestimated the actual volume by as much as 88.7% at lower volumes and underestimated the actual volume by as much as 53.9% at higher volumes. CONCLUSIONS: Differences in measurement error between the other ultrasonographic methods and the amniotic fluid index did not appear to be sufficient to warrant changes in current clinical practice. A major source of error in ultrasonographic amniotic fluid volume assessment is that one dimensional measurements are used to estimate the volume of a complex, three dimensional object. PMID- 1415439 TI - Do semiquantitative amniotic fluid indexes reflect actual volume? AB - OBJECTIVE: Our objective was to determine how well semiquantitative ultrasonographic measures of amniotic fluid, i.e., maximal amniotic fluid vertical pocket and amniotic fluid index, reflect actual amniotic fluid volumes in 50 near-term patients whose amniotic fluid volume estimates were normal by visual inspection. STUDY DESIGN: Before amniocentesis for fetal lung maturity, each patient had visual amniotic fluid volume estimates, maximal amniotic fluid vertical pocket, and amniotic fluid index performed by the same examiner, and then each received intraamniotic injection of a 10% paraaminohippurate solution. Amniotic fluid volume was quantitated by spectrophotometric assay of paraaminohippurate concentration. Oligohydramnios and polyhydramnios were defined as < 300 and > 2000 ml, respectively. RESULTS: Quantitative amniotic fluid volume was positively related to both amniotic fluid index and maximal amniotic fluid vertical pocket (r = 0.75 and 0.60, respectively). True-positive rates for oligohydramnios (amniotic fluid index < 5 cm or maximal amniotic fluid vertical pocket < 2 cm) were 100% and 0%, respectively; false-positive rates with either method were 0%. True-positive rates for polyhydramnios (amniotic fluid index > 20 cm and maximal amniotic fluid vertical pocket > 8 cm) were 0%; false-positive rates were 16% and 24%, respectively. CONCLUSIONS: Amniotic fluid index appears to be slightly better than maximal amniotic fluid vertical pocket for reflecting actual amniotic fluid volume. Both indirect methods tend to overestimate actual amniotic fluid volume at the upper end of its extremes. PMID- 1415440 TI - Contraceptive use projections: 1990 to 2010. AB - Factors that will affect both contraceptive use and choice of method during the next 20 years are reviewed. Two factors are predictable: the changing age distribution of women and the revised upper-age limits for oral contraceptive use, with the effect of the latter as yet unknown. Less predictable factors include the number of women in each age group at risk for pregnancy, the effects of delayed childbearing and sterilization, and the impact of new contraceptive methods. Unpredictable factors include adverse publicity about oral contraceptives and breast cancer, concern about sexually transmitted diseases and acquired immunodeficiency syndrome, and changes in the availability of legal abortion. Numbers of women using oral contraception, other reversible methods, sterilization, and no method are projected from 1990 to 2010 under the assumption that use patterns in each age group resemble those observed in 1988. We conclude that discrepancies between projections of contraceptive use and fact are likely to occur because of the unpredictable nature of these few important variables. PMID- 1415441 TI - Epidemiology of the noncontraceptive effects of oral contraceptives. AB - Epidemiologic studies have made major contributions to our understanding of oral contraceptive safety. The findings of major studies of the risk of cardiovascular disease and neoplasia associated with oral contraceptive use are reviewed, with discussion of the many factors to be considered in the interpretation of conflicting results. Mortality data that were based on earlier oral contraceptive formulations, dosage, and usage patterns may not be relevant to current practices. Recent studies suggest that reduced doses of estrogens and progestins in current oral contraceptive formulations and better screening of patients have reduced the risks of cardiovascular disease associated with oral contraceptive use, with the most important exception being an increased risk among older women who smoke. While most epidemiologic studies demonstrate no overall association between oral contraceptives and breast cancer, unanswered questions remain concerning this relationship. PMID- 1415442 TI - Oral contraceptives and gynecologic cancer: an update for the 1990s. AB - The most recent statistical evidence confirms a protective effect of oral contraceptive use against ovarian and endometrial cancers. Studies of the association between oral contraceptive use and cervical cancer continue to be hampered by confounding factors; however, results suggest that the overall risk of invasive cervical neoplasia is not increased. Although the association between oral contraceptive use and breast cancer remains controversial, existing data strongly suggest that overall risk of breast cancer is not increased by the use of oral contraceptives. In most candidates for oral contraceptive use, the benefits greatly outweigh the risks. PMID- 1415443 TI - The metabolic impact of oral contraceptives. AB - The hormonal components of oral contraceptives exert major effects on plasma lipoprotein metabolism. Estrogens may increase production of plasma triglycerides, leading to increased levels of very low-density lipoproteins, but they may also reduce levels of cholesterol-enriched and potentially atherogenic intermediate- and low-density lipoproteins. Furthermore, estrogens increase levels of high-density lipoproteins (HDLs), particularly the HDL2 subspecies, an effect linked to reduced mortality rates from cardiovascular disease in postmenopausal women receiving hormone replacement therapy. All combination oral contraceptives in use in the United States tend to raise levels of plasma triglycerides, low-density lipoprotein, and HDL3 to varying degrees. In contrast, changes in HDL and HDL2 reflect the combined effects of estrogen dose and relative androgenicity of the progestin component. Although in general, the lipoprotein changes are greater in magnitude with higher dose oral contraceptive preparations, they can be significant in lower dose preparations as well. Oral contraceptives also affect carbohydrate metabolism, primarily through the activity of progestin. Studies have demonstrated insulin resistance, rises in plasma insulin, and relative glucose intolerance by means of curve analysis of glucose tolerance tests. These effects are far less pronounced with lower dose preparations and with formulations using the newer progestins. PMID- 1415444 TI - Recent advances in understanding clotting and evaluating patients with recurrent thrombosis. AB - Significant advances have been made in defining the regulatory mechanisms that control blood clotting. These are reviewed, with special attention to the functions of the natural inhibitors antithrombin III, protein C, and protein S. Congenital deficiencies of these inhibitors as well as acquired abnormalities, such as defective fibrinolysis, and their role in promoting thrombosis are also discussed, as are thrombotic complications of pregnancy. Pregnancy decreases levels of protein S to 40% to 50% of normal levels. The decrease occurs early in pregnancy and persists into the postpartum period; it appears to be a hormonal rather than a dilutional effect. It is not known whether the thrombotic risk associated with pregnancy is increased in women who are congenitally deficient in protein S. Oral contraceptives decrease levels of protein S by about 20%. Women with a personal or family history of thrombosis should be evaluated for predisposing conditions before they start an oral contraceptive, as should women taking oral contraceptives who develop deep venous thrombosis. PMID- 1415445 TI - Preclinical evaluation of norgestimate, a progestin with minimal androgenic activity. AB - Norgestimate is a novel progestin with highly selective progestational activity and minimal androgenicity. In rabbits, norgestimate binds to uterine progestin receptors, stimulates the endometrium, and inhibits ovulation. Norgestimate acts directly on target organs, stimulating rabbit endometrium when injected into the uterine cavity and inhibiting luteinizing hormone-releasing hormone-stimulated luteinizing hormone release in dispersed rat pituitary cells in culture. Norgestimate has no estrogenic activity, and like other progestins, it suppresses the action of estrogen. Unlike some other progestins, it is relatively free of androgenic activity. Norgestimate and its 17-deacetylated metabolite demonstrate very poor affinity for androgen receptors compared with levonorgestrel and gestodene and do not exhibit androgenic activity when measured as the stimulation of prostatic growth in immature rats. Norgestimate's lack of affinity for human sex hormone-binding globulin is further evidence of its minimal androgenicity. PMID- 1415446 TI - A norgestimate-containing oral contraceptive: review of clinical studies. AB - Despite the well-documented efficacy and safety of low-dose oral contraceptives, the development of newer formulations containing highly selective progestins with minimal or no androgenic activity has been a goal of pharmaceutical research. The efficacy and safety of norgestimate, a progestin with inherently low androgenicity, in combination with ethinyl estradiol, has been examined in several phase II and phase III clinical studies, and these are reviewed. Norgestimate/ethinyl estradiol has proved to be a low-dose oral contraceptive with high selectivity that provides the cycle control of older oral contraceptive formulations with comparable efficacy. Results of comparison studies between norgestimate/ethinyl estradiol and formulations containing norgestrel, a progestin with relatively greater androgenic activity, in combination with ethinyl estradiol, are reported for effects on lipid and lipoprotein levels and carbohydrate metabolism. Norgestimate/ethinyl estradiol consistently produced statistically significant increases in high-density lipoprotein cholesterol and improvement in the ratio of low-density lipoprotein cholesterol to high-density lipoprotein. In contrast, norgestrel/ethinyl estradiol produced statistically significant decreases in high-density lipoprotein cholesterol and potentially adverse changes in the low-density/high-density lipoprotein ratio. Phase II studies have confirmed that norgestimate/ethinyl estradiol has low androgenic activity and causes minimal effect on coagulation factors and carbohydrate metabolism. PMID- 1415448 TI - Intraocular lens power calculations for multifocal intraocular lenses. AB - We performed calculations for anterior and posterior chamber intraocular lenses, determining the necessary power for emmetropia and 3 diopters of myopia for various axial lengths and corneal powers. Our results demonstrate that to achieve an effective add of 3.00 diopters at the spectacle plane (reading distance of 33 cm), the fabricated add (labeled add) on an intraocular lens must vary from 3.3 diopters for an anterior chamber lens in a patient with a flat cornea, to 5.1 diopters for a posterior chamber lens in a patient with a steep cornea. For most patients, targeting for an effective add of 3 diopters is appropriate, but factors such as availability of fabricated adds from the manufacturer and unusual patient requirements for near vision, may alter this target. We reviewed alternatives with monofocal lenses, such as monovision and compound myopic astigmatism. PMID- 1415447 TI - Glove perforations in ophthalmic surgery. AB - To determine the potential rate of intraoperative parenteral exposure of physicians and patients caused by glove perforation during ophthalmic surgery, gloves were analyzed after 125 procedures. Gloves were collected from all surgical team members (surgeon, assistants, scrub nurse, and circulating nurse). The rate of glove perforation was significantly lower for the surgeon, 0.3% (one of 303 gloves) than for the assistants, 5% (ten of 202 gloves [P = .001]), scrub nurses, 16% (52 of 326 gloves [P = .0001]), and circulating nurses, 15% (43 of 293 gloves [P = .0001]); similarly, assistants had a significantly lower rate than did scrub nurses (P = .0001) and circulating nurses (P = .001). There was no statistically significant difference in number of perforations on the basis of surgery duration or type of ophthalmic procedure. These findings suggest that the risk of parenteral exposure during ophthalmic surgery is low for the surgeon, and higher for other surgical personnel. We also analyzed additional safety precautions. Further study is warranted to determine the effectiveness of precautions and to guide policy formulation. PMID- 1415449 TI - Results of late surgery for presumed congenital cataracts. AB - We reviewed the results of cataract extraction and visual rehabilitation in 76 eyes of 47 infants and children with presumed congenital cataracts who were first seen after they were 10 months old. Eighteen patients underwent surgery for unilateral cataracts, including five patients with persistent hyperplastic vitreous, five with posterior lenticonus, one with a nuclear cataract, six with posterior subcapsular cataracts, and one with a lamellar cataract. Of these 18 patients, seven (39%) attained a visual acuity of 20/60 or better, one (6%) had a visual acuity of 20/100, and ten (60%) had a visual acuity of 20/200 or worse. Twenty-nine patients (62 eyes) underwent bilateral cataract extraction. The visual acuity could be measured in 22 patients (44 eyes). Visual acuity improved to 20/60 or better in 32 eyes (73%), was between 20/70 and 20/150 in 11 eyes (25%), and became worse than 20/200 in one eye (2%). Results were good in patients with persistent hyperplastic primary vitreous, posterior lenticonus, and bilateral cataracts. PMID- 1415450 TI - The Tokyo Metropolitan Home Vision Screening Program for amblyopia in 3-year-old children. AB - In August 1989, the Tokyo Metropolitan Government officially began a vision screening program for children aged 3 years 1 month. A 1988 pilot study of 1,303 children this age disclosed five cases (0.38%) of amblyopia. The home vision test, which uses picture cards of familiar figures, proved to be an efficient and inexpensive method of screening when incorporated into the existing health-check program for 3-year-old children. In the initial eight months of the program, 21,906 children were screened. Of these, 419 children (1.9%) were referred to an ophthalmologist for follow-up, and amblyopia was detected in 41 children (0.19%). PMID- 1415451 TI - Ocular hydrofluoric acid burns. AB - A 30-year-old man sustained exposure of his eyes, face, and neck involving 4% of body surface area to hydrofluoric acid. He was treated with immediate lavage and topical calcium gluconate. Because free fluoride ions from ocular and facial exposures can form complexes with body stores of calcium and magnesium, the patient was transferred to a burn unit for cardiac and electrolyte monitoring. He was also treated with calcium gluconate skin injections, pulmonary nebulizer therapy, and topical antibiotics and corticosteroids. In another case, a 25-year old man with less severe exposure to hydrofluoric acid was treated as an outpatient with topical antibiotics, corticosteroids, and cycloplegia. If an ophthalmologist is the first to treat a patient with chemical exposure, the history of hydrofluoric acid exposure must be obtained, and the burn team and other medical specialists must be quickly consulted to avoid potentially fatal complications. PMID- 1415452 TI - Stray light in radial keratotomy and the influence of pupil size and straylight angle. AB - Glare is a major sequela of the radial keratotomy procedure. We used the straylight meter to measure intraocular light scatter, which is the cause of glare, in eyes after radial keratotomy. This apparatus uses a direct compensation method to assess the amount of intraocular light scatter. Nineteen patients were tested. Nine individuals served as controls. The mean postsurgery time was 60 months. The influence of the number of radial incisions, the pupil size, and the angle of light entering the eye were evaluated with the straylight meter. The results showed straylight values for normal pupil size (mean, 4 mm) to be statistically significantly higher (P = .0044) only for the smallest angle of light deflection studied (3.5 degrees). For dilated pupils (mean, 8 mm), straylight values were statistically significantly higher (P = .00005) for all three angles of light deflection studied. The number of incisions showed no statistically significant relationship to straylight values. Average stray light values were increased by a factor of 1.4 for 4-mm sized pupils and 2.0 for 8-mm sized pupils. There was an overlap in straylight values between the patient population and the control population. PMID- 1415453 TI - Photorefractive keratectomy for severe postkeratoplasty astigmatism. AB - We performed cylindric corneal ablations with the excimer laser on 12 patients to correct severe, disabling astigmatism after keratoplasty. In some patients, an additional ablation was performed to correct myopia. Patients were followed up for an average of eight months (range, six to 14 months). Uncorrected visual acuity improved in nine patients, and nine of the 12 patients had a decrease in refractive cylinder at last follow-up. The mean preoperative refractive cylinder was 7.0 +/- 3.6 diopters, which decreased to a mean of 3.1 +/- 2.6 diopters at one month (P = .0003) and 4.3 +/- 2.9 diopters at last follow-up (P = .03). Keratometric astigmatism decreased from 7.5 +/- 3.9 diopters preoperatively to 5.2 +/- 3.9 diopters at the last follow-up (P = .001). Mean spherical equivalent was reduced from -7.4 +/- 4.2 diopters preoperatively to -3.3 +/- 4.4 diopters postoperatively (P = .003). Postoperative corneal haze, when present, did not reduce visual acuity. Excimer laser superficial keratectomy thus appears to be safe when used for postkeratoplasty ametropia, although substantial regression may limit its effectiveness in some patients. PMID- 1415454 TI - Fungal keratitis from nylon line lawn trimmers. AB - Ocular trauma from nylon line lawn trimmers is becoming more prevalent. Previous case reports have described penetrating trauma caused by these tools. We managed three cases of fungal keratitis caused by injuries from nylon line trimmers. Fungal keratitis should be strongly considered as the cause of any corneal ulcer related to trauma from a nylon line lawn trimmer. PMID- 1415455 TI - Topical fibronectin in the treatment of keratoconjunctivitis sicca. Chiron Keratoconjunctivitis Sicca Study Group. AB - Topical fibronectin was evaluated for the treatment of keratoconjunctivitis sicca in a multicenter, double-masked, controlled study in which 272 patients were randomly assigned to treatment. Patients with documented clinical evidence of keratoconjunctivitis sicca received either fibronectin, a vehicle alone, or a commercially available artificial tear. Evaluation at baseline, 21, 42, and 63 days consisted of patient self-evaluation of symptoms, rose bengal and fluorescein staining, tear breakup time, Schirmer's testing, and conjunctival impression cytology. Although all groups showed improvements in most study variables during the course of the study, there were no statistically significant differences found between any of the groups. Topical fibronectin does not appear to be more effective than artificial tears in the treatment of keratoconjunctivitis sicca. PMID- 1415456 TI - Progression of nonproliferative diabetic retinopathy and visual outcome after extracapsular cataract extraction and intraocular lens implantation. AB - Twenty-one patients with symmetric nonproliferative retinopathy who underwent extracapsular cataract extraction and intraocular lens implantation were followed up postoperatively for an average (+/- standard deviation) of 18 +/- 7 months to determine the incidence of progression of diabetic retinopathy, the final visual acuity, and factors predictive of progression of retinopathy and final visual acuity. Progression of retinopathy, defined as the development of clinically significant macular edema, an increase in intraretinal hemorrhages or hard exudate, or the development of proliferative diabetic retinopathy, was assessed in both eyes of 19 patients; in two remaining patients, dense preoperative cataract in the fellow eye precluded comparison of retinopathy progression in the operated-on eye to progression in the fellow eye. Overall, retinopathy progressed in 14 of 19 operated-on eyes (74%). Cataract extraction was highly associated with asymmetric progression of nonproliferative retinopathy; it progressed only in the operated-on eye in seven of 19 patients (37%), but in no patients did progression occur in the fellow eye alone (P = .0078). Women had a significantly increased risk of progression of retinopathy in the operated-on eye compared to men (P = .005). Visual acuity improved in 19 of 21 operated-on eyes (86%); however, only 11 eyes (52%) achieved a visual acuity of 20/50 or better and only six eyes (14%) achieved a visual acuity of 20/25 or better. In only five eyes was the final visual acuity in the operated-on eye more than two lines better than the final visual acuity in the fellow eye.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415457 TI - Efficacy of fluid-air exchange for postvitrectomy diabetic vitreous hemorrhage. AB - We reviewed the records of 33 fluid-air exchanges to assess the efficacy of fluid air exchange in the management of recurrent vitreous cavity hemorrhage after vitrectomy for proliferative diabetic retinopathy. Fluid-air exchange alone was successful in clearing the vitreous cavity in ten of 20 eyes after a mean of 1.5 exchanges per eye. Repeat vitrectomy was required in the remaining ten eyes and anterior hyaloidal fibrovascular proliferation was frequently found. Hemorrhages that occurred in the late postoperative period (more than nine months) appeared more likely to be successfully treated with fluid-air exchange alone. Failure of the initial fluid-air exchange to induce clearing immediately after the procedure appeared to be associated with subsequent exchange failures and need for surgical intervention. Complications from the exchange procedure were infrequent with the development of peripheral retinal detachment in one eye. Our current recommendation for nonclearing recurrent postvitrectomy diabetic vitreous hemorrhage is to perform a fluid-air exchange, provided no other high-risk characteristics are present. If clearing occurs in the immediate postexchange period but rebleeding occurs at a later period, we recommend a second fluid-air exchange. If clearing does not occur in the immediate postexchange period, we recommend proceeding directly to revision of vitrectomy. PMID- 1415458 TI - Immunohistochemical and histochemical properties of surgically excised subretinal neovascular membranes in age-related macular degeneration. AB - The immunohistochemical and histochemical properties of 16 surgically excised subretinal neovascular membranes from 16 patients with age-related macular degeneration were studied. Primary antisera to c-retinaldehyde-binding protein; leukocyte common antigen; factor VIII-related antigen; S-100 protein; glial fibrillary acid protein; muscle-specific actin; neuron-specific enolase; collagen types I, II, III, IV, and V; laminin; and fibronectin were used for immunohistochemical characterization of the membranes. Histochemical staining for lipid and mucopolysaccharide was performed. The results of the staining in conjunction with histologic examination showed the cellular components of the membranes to be composed of retinal pigment epithelium, inflammatory cells, vascular endothelium, glial cells, myofibroblasts, photoreceptor cells, and fibrocytes. The extracellular matrix of the membranes contained collagen types I, III, IV, and V; fibronectin; laminin; mucopolysaccharide; and lipid. These findings are consistent with the concept that subretinal neovascular membranes in age-related macular degeneration are composed of localized intra-Bruch's membrane granulation tissue proliferation associated with diffuse drusen. PMID- 1415459 TI - Aqueous dynamics in exfoliation syndrome. AB - Eighteen untreated patients with unilateral exfoliation syndrome without glaucoma were studied with regard to differences in aqueous dynamics between the affected and unaffected fellow eyes. Additionally, both eyes of the patients with exfoliation were compared to the eyes of 18 age-matched and gender-matched control subjects. Intraocular pressure was significantly higher (13.9 +/- 3.0 mm Hg [mean +/- standard deviation]) in the affected compared with the unaffected eyes (12.2 +/- 2.5 mm Hg), but no difference in aqueous humor flow was detected when eyes in the three groups were compared (affected eyes, 2.40 +/- 0.60 microliter/min; unaffected eyes, 2.40 +/- 0.65 microliter/min; control eyes, 2.61 +/- 0.60 microliter/min). Anterior chamber volumes were significantly smaller in affected (122 +/- 37 microliters) and unaffected eyes (121 +/- 37 microliters) of the patients with exfoliation compared with the eyes of the control subjects (145 +/- 30 microliters). Apparent resistance was higher in the eyes with exfoliation (6.5 +/- 1.9 min mm Hg/microliters) compared with both unaffected (5.4 +/- 1.2 min mm Hg/microliters) and control groups (5.2 +/- 1.8 min mm Hg/microliters), although these differences were not statistically significant. PMID- 1415460 TI - Intraocular pressure decrease in household contacts of patients with Hansen's disease and endemic control subjects. AB - We compared the intraocular pressure in 150 urban household contacts of patients with Hansen's disease and 132 endemic control subjects from an urban population in Karachi, Pakistan, who were matched in regard to race, age, gender, and socioeconomic status. The mean intraocular pressure in the upright position was 12.6 mm Hg in the right eye and 12.9 mm Hg in the left eye in household contacts of patients with Hansen's disease and 15.3 mm Hg in the right eye and 15.4 mm Hg in the left eye in the endemic control population (P < .0005). The postural change in intraocular pressure from the upright to supine position was 1.7 mm Hg in the right eye and 2.1 mm Hg in the left eye in the household contacts group and 1.3 mm Hg in the right eye and 1.5 mm Hg in the left eye in the endemic control group (P < .0006). Our findings, especially in view of past observations in intraocular pressure changes in patients with Hansen's disease, raise serious questions about possible early ocular susceptibility to Mycobacterium leprae infection and about public health issues, including possible early indication of disease. PMID- 1415461 TI - Asymmetric pigmentary glaucoma resulting from cataract formation. AB - Pigment dispersion syndrome usually manifests bilaterally, and asymmetric involvement is unusual. When asymmetry is present, the eye with greater involvement may have an additional exacerbating condition or the eye with less involvement may be protected. Analysis of such cases should further elucidate the mechanism of the disorder and its development and regression. We examined four patients in whom unilateral cataract formation or extraction was associated with reduced clinical signs of pigment dispersion syndrome in the affected eye. Cataract formation, by inducing relative pupillary block, appears to decrease or prevent the manifestation of pigment liberation. PMID- 1415462 TI - The edrophonium-Hess screen test in the diagnosis of ocular myasthenia gravis. AB - The interpretation of the edrophonium (Tensilon) test in the diagnosis of acquired strabismus caused by myasthenia gravis has been problematic because of poorly defined endpoints and unknown sensitivity and specificity. We evaluated the endpoint criteria, dynamics, sensitivity, and specificity of binocular alignment in response to edrophonium by using the Hess screen test in ten normal control subjects, 12 nonmyasthenic patients with acquired strabismus, and in ten patients with acquired strabismus caused by ocular myasthenia gravis. A positive response to the edrophonium-Hess screen test was defined as a 50% or greater reduction in the strabismic deviation at the fixation point associated with maximum deviation within one minute of edrophonium infusion. All myasthenic patients had a 50% or greater reduction in the initial deviation within one minute of edrophonium infusion. Myasthenic patients had a statistically significant reduction in the average deviation up to 150 seconds after edrophonium infusion (P < .05 for all time periods). In contrast, with or without edrophonium infusion, control subjects had a purely horizontal fluctuation in binocular alignment of less than or equal to 2 degrees for the entire four-minute period after edrophonium infusion. None of the 12 nonmyasthenic patients tested positive to the edrophonium-Hess screen test. According to the criterion of positive response as was defined in this study, the test had a high sensitivity and specificity in this sample. These results suggest that clearly defined endpoint criteria make the edrophonium-Hess screen test a sensitive and specific quantitative study for the diagnosis of acquired strabismus caused by myasthenia gravis. PMID- 1415463 TI - Neuro-ophthalmic associations and complications of diabetes mellitus. PMID- 1415464 TI - Use of the potential acuity meter in suspected functional visual loss. PMID- 1415465 TI - Corneoscleral, ciliary body, and vitreoretinal toxicity after excessive instillation of mitomycin C. PMID- 1415466 TI - Pure ocular blast injury. PMID- 1415467 TI - Mild frosted branch periphlebitis. PMID- 1415468 TI - Retinal neovascularization and cystoid macular edema in punctata albescens retinopathy. PMID- 1415469 TI - Subretinal diathermy probe. PMID- 1415470 TI - Idiopathic alternating anisocoria. PMID- 1415471 TI - Inflammatory orbital tumor as an ocular sign of a battered child. PMID- 1415472 TI - Periosteal flap for lower eyelid reconstruction. PMID- 1415473 TI - Ultrasound biomicroscopy of anterior segment structures in normal and glaucomatous eyes. PMID- 1415474 TI - Amyloidosis in aging and Alzheimer's disease. PMID- 1415475 TI - A stem cell niche theory of intestinal crypt maintenance based on a study of somatic mutation in colonic mucosa. AB - In both large and small intestine, mutagen administration leads to the occurrence of isolated crypts that are completely populated by a mutated phenotype; therefore, it has been proposed that crypts are maintained by a single stem cell. We show in mice that a single dose of mutagen leads to an early transient increase in frequency of colonic crypts that show a partial mutated phenotype and a later increase in frequency of crypts that show a complete mutated phenotype. This increase reaches a plateau at about the same time as the disappearance of partially mutated crypts. The same is true in the small intestine, but the time course is much slower. We propose an explanation based on multiple crypt stem cells that occupy a "stem cell niche," with random cell loss after stem cell division. A small difference in the number of crypt stem cells that occupy the niche provides a simple explanation for the surprisingly large difference in the time course of phenotypic changes in the large and small intestines after administration of a single dose of mutagen. PMID- 1415476 TI - A (CA)n dinucleotide repeat assay for evaluating loss of allelic heterozygosity in small and archival human brain tumor specimens. AB - Southern blotting is a widely used method of determining loss of chromosomal alleles in tumors, but cannot be used to analyze small biopsies and most fixed, embedded tissues. These problems preclude analysis of many surgical neuropathology specimens. We have employed a polymerase chain reaction assay for loss of heterozygosity (LOH) based on the (CA)n dinucleotide repeat polymorphisms found in abundance throughout the human genome. We compared this method to conventional Southern blotting in detecting LOH on chromosome 10 in gliomas. From tissue sections of 14 paraffin-embedded, formalin-fixed gliomas, we amplified the (CA)n repeat D10S89 locus and compared (CA)n repeat patterns between tumor DNA and constitutional DNA. Loss of one chromosome 10 (CA)n repeat allele was seen in informative glioblastomas that showed allelic loss by Southern blotting, but not in gliomas that had maintained both alleles. The (CA)n repeat method can be applied to small and fixed, embedded specimens, is rapid and simple to perform, and uses highly polymorphic probes. We suggest that (CA)n repeats are a less exclusive and more rapid means of studying LOH in brain tumors than Southern blotting, and will provide further mapping data for the identification of tumor suppressor genes integral to glial tumorigenesis. PMID- 1415477 TI - Immunohistochemical identification of thrombospondin in normal human brain and in Alzheimer's disease. AB - Thrombospondin is part of a family of adhesive glycoproteins and is involved in a number of physiologic processes such as angiogenesis and neurite outgrowth. Immunohistochemical localization of thrombospondin in normal human brains was investigated in the hippocampus and inferior temporal cortex. Two antibodies (one polyclonal and one monoclonal) against thrombospondin-labeled microvessels, glial cells, and a subpopulation of pyramidal neurons. The distribution of thrombospondin staining in patients with Alzheimer's disease was found to be comparable to control subjects. However, in patients with Alzheimer's disease a subset of pyramidal neurons that may be vulnerable in Alzheimer's disease exhibited decreased staining. This decrease in the intensity of labeling might constitute a marker for a neuronal population prone to early degeneration. In addition, thrombospondin staining was demonstrated in senile plaques in Alzheimer's disease. These results suggest that thrombospondin may be involved in the process of neuronal degeneration and senile plaque formation. PMID- 1415478 TI - The altered glomerular filtration slits seen in puromycin aminonucleoside nephrosis and protamine sulfate-treated rats contain the tight junction protein ZO-1. AB - Nephrosis induced in rats by puromycin aminonucleoside treatment (PAN) results in the apical displacement of the glomerular filtration slit membrane by newly formed, intercellular occluding-type junctions. Similar changes can also be induced by acute kidney perfusion with protamine sulfate (PS). We have investigated the molecular nature of these altered junctions using an antibody to ZO-1, a protein found exclusively in tight junctions. Immunoblotting demonstrates ZO-1, a 225-kd band, in glomerular extracts of normal, PAN-, and PS-treated rats. By immunofluorescence, ZO-1 was localized at the base of podocytes outlining the capillary loops of glomeruli from all three experimental groups. At the electron microscope level, using immunoperoxidase or immunogold labeling, ZO-1 was concentrated along the cytoplasmic surfaces of the slit diaphragms of normal rats. In PAN or PS rats, it was concentrated along both the newly formed occluding-type junctions and the remaining slit diaphragms. When podocalyxin (the major membrane sialoprotein of the podocyte) was similarly localized, it was found exclusively apical to the displaced slit membrane. Based on morphology and the presence of ZO-1, the altered junctions seen in PAN and PS rats appear to represent bona fide tight junctions. Their rapid (15-minute) induction in PS treated rats suggests that on neutralization of the cell surface charge by polycation perfusion, discontinuous tight junctions form from a preexisting pool of junctional proteins. These findings raise the possibility that glomerular hydraulic conductivity may be regulated in part by regulating the relative patency and width of the filtration slits through focal tight junction assembly. PMID- 1415479 TI - Association of murine CD31 with transmigrating lymphocytes following antigenic stimulation. AB - Human CD31 is a recently characterized molecule present on leukocytes, platelets, and endothelium. Its function is not known. Because it is a member of the immunoglobulin superfamily and structurally homologous to carcinoembryonic antigen, a putative intercellular adhesion molecule, it is believed that CD31 may function also as an adhesion molecule. In this report, we characterize the cellular reactivity of a monoclonal antibody to a murine protein that is homologous to CD31. To delineate the cellular reactivity of the murine CD31 homologue recognized by our monoclonal antibody, we used immunoperoxidase and immunoelectron microscopic techniques. The most striking finding was that the putative murine homolog of CD31 is expressed in particularly high amounts on endothelium-adherent lymphocytes transmigrating across sinusoidal or venular vascular boundaries. Such a distribution was apparent in draining murine lymph nodes during the peak of an immune response after immunization with a protein antigen in adjuvant, a situation in which there are many transmigrating lymphocytes. Immunoelectron microscopic analysis also shows that CD31 is predominantly distributed on portions of transmigrating lymphocytes that are in contact with or adjacent to areas of contact with endothelial cells. These findings suggest a previously undescribed role for CD31 in lymphocyte recruitment and transmigration. PMID- 1415481 TI - The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. AB - Using immunohistochemistry or Western blot analysis, the authors have studied the expression of the Hu antigen (a neuronal protein identified by the serum of patients with small cell lung cancer and paraneoplastic encephalomyelitis/sensory neuronopathy) in normal human tissues and 115 tumors of different histologic types. In normal tissue, the Hu antigen is highly restricted to the nervous system. In lung tumors, the Hu antigen is restricted in its expression to all small cell carcinomas. A few other neuroendocrine-related tumors, especially neuroblastomas (50%), also express the antigen. PMID- 1415480 TI - Immunoelectrophoretic and immunohistochemical characterizations of fibrinogen derivatives in atherosclerotic aortic intimas and vascular prosthesis pseudo intimas. AB - Cadaveric aortic intimas with uncomplicated atherosclerosis were examined to determine the distribution and polypeptide chain composition of fibrinogen related protein. Immunohistochemical staining showed deposits rich in fibrinopeptides A and B. The deposits were usually disseminated throughout intimas of moderate thickness < 0.7 mm, but were distributed focally in elongate patches bounded both lumenally and medially by deposit-free tissue in thick atheromas. Saline extracts generally showed undegraded monomers and dimers by electrophoresis. The residual protein contained A alpha and gamma-chains that were cross-linked predominantly (>80%) into unresolved high M(r) (>200 kd) derivatives, whereas B beta-chains were left non-cross-linked, as occurs in late stages of cross-linking by transglutaminases. The resolved components had electrophoretic mobilities corresponding to characteristic products of both factor XIIIa and tissue-transglutaminase. A greater incorporation of alpha- rather than gamma-chains into cross-linked products implicated tissue transglutaminase as contributing heavily. By contrast, vascular graft pseudo intimas and a cadaveric clot were rich in degraded fibrin devoid of fibrinopeptide A, and cross-linked in patterns typical of XIIIa with gamma 2 dimers constituting the principal product. The findings indicate that the fibrinogen in the aortic intima is comparatively well protected from thrombin and plasmin, and that much of it is deposited through direct cross-linking by tissue transglutaminase without being converted to fibrin. PMID- 1415482 TI - Glomerular macrophages and the mesangial proliferative response in the experimental nephrotic syndrome. AB - Mesangial cell proliferation, which is a harbinger of glomerulosclerosis, occurs in both immune and nonimmune glomerulopathies. The proximity of infiltrating glomerular macrophages to the contractile mesangial cells during acute puromycin aminonucleoside (PA) nephrosis suggests the possibility of a paracrine effect on mesangial cell growth. To test this, three maneuvers to either raise or lower the glomerular macrophage number during acute PA nephrosis (2 weeks after PA) were employed: 1) an essential fatty acid-deficient (EFAD) diet; 2) a cholesterol supplemented diet (CSD); and 3) a single dose (600 rad) whole-body X-irradiation (XI) given to CSD-fed PA rats. Both the glomerular macrophage number and proliferation within the mesangium were evaluated immunohistochemically with ED 1, a mouse monoclonal anti-rat macrophage label, and 19A2, a mouse monoclonal anti-proliferating cell nuclear antigen (PCNA)/cyclin antibody, respectively. Immunohistochemical detection of 5'-bromo-2'-deoxyuridine (BrdU) incorporation confirmed that proliferation was occurring within the mesangial zones. The EFAD diet significantly reduced both the glomerular macrophage and PCNA/cyclin positive cell number at 2 weeks after PA with a positive correlation (r = 0.89, P < 0.05). The CSD maneuver significantly increased both the glomerular macrophage and PCNA/cyclin cell number with a strong degree of correlation (r = 0.95, P < 0.01). X-irradiation administered to CSD-fed PA rats significantly lowered both the glomerular macrophage and PCNA/cyclin-positive cell number at 2 weeks. In all groups, the glomerular tufts did not express muscle actin using HHF 35, a specific immunolabel, suggesting that the proliferation in this model is not related to direct mesangial cell injury. This study shows that maneuvers that modulate the glomerular macrophage number are also associated with corresponding changes in the number of proliferating cells within the mesangium, suggesting a paracrine growth stimulation by the infiltrating macrophage during acute PA nephrosis. The infiltrating glomerular macrophage may be an effector mechanism for the propagation of initial glomerular injury to glomerulosclerosis by augmenting mesangial cell proliferation early in the course of this nonimmune progressive glomerulopathy. PMID- 1415483 TI - Morphologic effects of hGRH gene expression on the pituitary, liver, and pancreas of MT-hGRH transgenic mice. An in situ hybridization analysis. AB - Morphologic changes in the pituitary, liver, and pancreas of mice with the metallothionein-human growth hormone--releasing hormone (MT-hGRH) transgene were analyzed by in situ hybridization histochemistry (ISH). There was progression from somatotroph hyperplasia to neoplasia in pituitaries of transgenic mice. Pituitary neoplasms were present between 9 to 12 months of age in some mice. Magnetic resonance imaging (MRI) readily identified enlarged pituitaries in MT hGRH transgenic mice. Serum mouse GH and hGRH levels were marked elevated in MT hGRH transgenic mice. In situ hybridization histochemistry showed mRNA for hGRH in liver, pituitary, pancreas, spleen, and in most other tissues examined. Combined ISH and immunohistochemistry in the pituitary gland showed that some of the GH cells also produced hGRH, and ultrastructural immunohistochemical analysis of pituitaries showed that GH and hGRH were localized in the same cell and within the same secretory granules. Liver cells of MT-hGRH transgenic mice showed evidence of hypertrophy, and the pancreatic islets were hyperplastic with significant increases in the islet cell areas. The morphologic changes in the liver were distinctive enough to separate control littermates from MT-hGRH transgenic mice in all cases. The enlarged pancreatic islets had increased numbers of insulin-producing cells. Immunoreactive hGRH and hGRH mRNA were both localized in islet cells, and an intense hybridization signal of hGRH mRNA, but only weak staining for hGRH protein, were detected in the liver of transgenic mice. These results indicate that excessive hGRH production leads to distinct morphologic changes in various organs in MT-hGRH transgenic mice and that there is temporal progression from hyperplasia to adenomatous somatotrophs in pituitaries with chronic stimulation by hGRH that involves paracrine, endocrine, and autocrine mechanisms. PMID- 1415484 TI - Functional heterogeneity and pathogenic significance of interleukin-6 in B-cell lymphomas. AB - A possible autocrine effect of interleukin-6 (IL-6) on the growth and differentiation of the tumor cells of 55 B-cell lymphomas was examined. Interleukin-6 was detected in a few types of B-cell lymphomas, including polymorphic immunocytoma (PI), small lymphocytic lymphoma (SLL), and immunoblastic lymphoma (IBL) with or without plasmacytoid differentiation. In PI and in IBL with plasmacytoid differentiation (IBL-P), IL-6 was detected only in immunoglobulin-containing plasmacytoid cells, and it was absent from most proliferating (Ki-67/PCNA-positive) lymphoma cells. In SLL, IL-6 was not observed in lymphoplasmacytoid cells; instead, IL-6 was observed in transformed (Ki 67/PCNA-positive) tumor cells in proliferation centers. The lymphoplasmacytoid cells in SLL exhibited a phenotype (IL-6/glutathione-S-transferase-pi [GST-pi] negative), different from that of normal plasma cells (IL-6-negative/GST-pi positive) and from the plasmacytoid cells (IL-6/GST-pi-positive) in PI and IBL-P. In IBL without obvious plasmacytoid differentiation, IL-6 was detected in most tumor cells that were highly proliferative (Ki-67/PCNA-positive). In this study, IL-6 was undetectable in most lymphomas related to follicular centers, in lymphoblastic lymphoma, in small noncleaved cell lymphomas of the Burkitt and non Burkitt types, and in diffuse large cell lymphoma. This finding is compatible with a previous finding that IL-6 mRNA was absent from follicular center cells in reactive lymphoid tissues. The functions of IL-6 in these lymphomas may be quite diverse. It appears that IL-6, as an autocrine factor, is responsible for the plasmacytoid differentiation of lymphoma cells in IP and some IBL (IBL-P). The differentiation of lymphoplasmacytoid lymphoma cells in SLL, however, may not be mediated by an autocrine IL-6 mechanism. Interleukin-6 may provide a growth signal, rather than acting as a differentiation factor, for some IBL cells and for some transformed tumor cells in proliferation centers in SLL. PMID- 1415485 TI - Early extracellular and cellular lipid deposits in aorta of cholesterol-fed rabbits. AB - Subendothelial accumulation of extracellular liposomes rich in unesterified cholesterol has been described as an early feature of atherosclerosis induced by cholesterol feeding in rabbits. Beta-very-low-density lipoproteins, however, the presumed source of atherogenic lipid in this animal model, contain mostly esterified cholesterol. The purpose of this study was to test for the presence of extracellular neutral lipid deposits consistent with esterified cholesterol, by employing new electron microscopic techniques. Rabbits were fed 0.5% cholesterol, 5% butter for 0, 1, 2, and 4 weeks. The lipid-preserving ultrastructural techniques showed, in control and atherosclerotic rabbit arteries, neutral lipid droplets adherent to the endothelial luminal surface. After 1 to 2 weeks, subendothelial extracellular deposits of mostly membranous lipid appeared; these deposits contained variable amounts of neutral lipid. At the same time, cytoplasmic neutral lipid droplets appeared in smooth muscle cells and in a small number of subendothelial macrophagelike cells. After 4 weeks, monocytic infiltration and macrophage foam cell development were prominent, but abundant extracellular lipid deposits also were found. Therefore, in arteries of cholesterol-fed rabbits, deposition of membranous and neutral lipid in the extracellular space and neutral lipid accumulation in resident arterial cells are early and probably independent events, both occurring before monocytic infiltration of the arterial intima. PMID- 1415486 TI - Proto-oncogene analysis in multiple myeloma. AB - The genetic basis for the development of multiple myeloma (MM) remains poorly understood, in part because MM has thus far been relatively refractory to cytogenetic analysis. The few cases karyotyped have pointed to involvement of 11q13, site of the BCL1 proto-oncogene, or of 8q24, site of the MYC proto oncogene. A recent molecular study detected rearrangements distal to the MYC gene in 16% of MM, using the MLVI-4 probe. The immunocytochemical demonstration of BCL2 protein overexpression in at least some cases of MM has suggested the possibility of translocation-mediated deregulation of the BCL2 proto-oncogene. The configuration of the BCL2 gene in MM, however, has not yet been defined using all available breakpoint probes. To address these issues, we studied 17 patients with plasma cell dyscrasias (16 MM, 1 plasmacytoma) by Southern blotting using the major breakpoint region (MBR), minor cluster region (MCR), and 5' cDNA (pB16) BCL2 breakpoint probes; with the BCL1 major translocation cluster (MTC) breakpoint probe; and with a probe to the MYC-associated MLVI-4 region (PA1.3SB). In all 17 cases, rearrangement of one or both alleles of the immunoglobulin heavy chain gene had been demonstrated, thereby confirming the presence of tumor DNA in the samples studied. None of the cases tested showed a rearrangement with the MBR BCL2 (0/16), MCR BCL2 (0/17), 5' cDNA BCL2 (0/16), BCL1 MTC (0/15), or MLVI-4 (0/15) probes. These results suggest that if BCL2 deregulation does indeed occur in MM, a mechanism other than translocation must be involved in most cases. Furthermore, rearrangements distal to the MYC gene, in the region of the MLVI-4 probe, may be less common than previously thought. Finally, a significant proportion of translocation breakpoints in band 11q13 may not be detected by the BCL1 MTC probe in MM, as is true in lymphomas. PMID- 1415487 TI - Vimentin metaplasia in renal cortical tubules of preneoplastic, neoplastic, aging, and regenerative lesions of rats and humans. AB - Vimentin expression was studied immunohistochemically in renal cortical tubules of untreated male rats of various ages, rats exposed to toxins (barbital sodium, folic acid) and carcinogens (streptozotocin, N-bis(2-hydroxypropyl)nitrosamine, barbital sodium, and in humans of various ages with or without renal epithelial tumors. Fetal, neonatal, and young adult rats did not express vimentin in renal cortical tubules. Regenerative renal tubular lesions from rats with aging nephropathy and from rats with toxic nephropathy both expressed vimentin. Mitogenic lesions induced by folic acid at 24 hours, however, were not immunoreactive for vimentin. Carcinogen-induced preneoplastic renal cortical tubular lesions in rats were most often focally immunoreactive whereas strong vimentin expression was found in almost all induced renal tumors. In kidneys of three children (younger than 2 years of age), vimentin was not found in renal cortical tubular cells except in rare individual cells in one case. Vimentin was abundant in basophilic regenerative tubules in kidneys of aged individuals, however. Most (7/10) human renal carcinomas and latent preneoplastic or neoplastic renal tubular lesions found incidentally at autopsy (2/4) showed vimentin expression. The authors suggest that the switching to vimentin expression in phenotypically normal renal cortical tubular cells in rats and humans, which do not usually express the intermediate filament protein vimentin, should be considered vimentin metaplasia. Vimentin expression is dissociated from increased cell proliferation in hyperplastic and neoplastic lesions, however. Instead the degree of dedifferentiation of the tubule cells and changes in phenotype were associated with vimentin expression. PMID- 1415488 TI - Expression of macrophage inflammatory protein-2 and KC mRNA in pulmonary inflammation. AB - This study sought to test the hypothesis that expression of mRNA for two cytokines, macrophage inflammatory protein-2 (MIP-2) and the KC gene product, is induced in rat lung cells during inflammatory responses in vitro and in vivo. Macrophage inflammatory protein-2 and KC are members of the platelet-factor 4 (PF 4) cytokine superfamily that cause marked neutrophil chemotaxis and activation in vitro. To investigate expression of the genes for MIP-2 and KC in rat models of lung injury, cDNA probes for these cytokines in the rat were made from polymerase chain reaction (PCR) products generated using mouse sequence-derived primers. Sequence analysis of these cDNAs showed marked homology to known murine sequences (89% and 92% MIP-2 and KC, respectively). These cDNAs were first used to study the expression of these two genes in rat alveolar macrophages (AMs) in vitro by Northern blot hybridization. Lipopolysaccharide (LPS) treatment of rat AMs in vitro caused marked increases in mRNA for both KC and MIP-2 within 30 minutes, which persisted through the 6 hours measured. To study expression during inflammation in vivo, rats were treated with LPS by intratracheal instillation. Bronchoalveolar lavage (BAL) cells and whole trachea homogenates were analyzed. There was a marked and rapid increase in MIP-2 and KC mRNA levels within both BAL cells and trachea homogenates after LPS instillation. The results support the hypothesis that MIP-2 and KC cytokines contribute to neutrophil chemotaxis and activation in this rat model of acute pulmonary inflammation. PMID- 1415489 TI - Neuronal injury after photoactivation of photofrin II. AB - Photodynamic therapy has been used in the management of patients with malignant brain tumors even though the effects of this form of treatment on the adjacent normal brain are incompletely characterized. The authors examined, in sequential experiments, morphologic alterations affecting the cerebral cortex in rats injected with Photophrin II and exposed to light. Initially, minimal cell alterations, including cisternal swelling of both endoplasmic reticulum and Golgi apparatus, involved only neurons located in the superficial layers of the cerebral cortex exposed to light. These changes spread, over a period of several hours, from the surface to the bottom of the cortex and eventually involved the entire cortical segment exposed to light. The earliest structural signs of lethal injury to neurons developed over a period of 18 hours after porphyrins had been photoactivated and astrocytes had been severely damaged. Signs of lethal injury to neurons included an increase in the number of mitochondrial cristae and appearance of amorphous electron-dense deposits within swollen mitochondria. The appearance of these alterations was followed by segregation of intracytoplasmic organelles and fragmentation of nuclear and cytoplasmic membranes. The tissue changes, including those involving neurons, eventually progressed to coagulation necrosis at 48 hours. These observations suggest that prophyrins injected to rats (48 hours before photoactivation) cause swelling and necrosis of astrocytes. This is followed by neuronal necrosis, which appears at two time intervals; the initial neuronal necrosis occurs after the astrocytic disintegration. A second type of neuronal alteration appears after microvessels become thrombosed and ischemia is likely to develop. PMID- 1415490 TI - Hyaluronan synthesis by in vitro cultured endolymphatic sac cells. AB - The endolymphatic sac (ELS) has been the subject of investigation for many years and yet its overall function remains unclear. It is believed mainly to be involved in the regulation of endolymph through fluid resorption and secretion of osmotically active substances. The present study was performed using in vitro cultured, fetal ELSs of 18 to 19 day gestational mice, to assess whether the ELS cells can synthesize the osmotically active polysaccharide, hyaluronan (HA). The ELS and portions of the membranous labyrinth were dissected from whole otocyst specimens and placed in 14C glucose-enhanced tissue culture media. A light microscopic (LM), autoradiographic study was performed to assess whether 14C glucose could be incorporated by the tissue into HA. Both the ELS cells and the adjacent cartilage demonstrated radiolabel incorporation within 4 hours of incubation in tissue culture medium, with increased radiolabel density in ELS cells after 24 hours of incubation. HA-specific hyaluronidase (HAase) resulted in removal of HAase-sensitive compounds in the ELS in both 4-hour and 24-hour cultured specimens when compared to adjacent cartilage cells (p = 0.001). Approximately 43 percent of the radiolabel was incorporated into HA in ELS specimens, as compared to a 22 percent HA synthesis in the adjacent cartilage tissue, suggesting preferential synthesis by ELS cells. The dissected murine otocysts demonstrate viability in vitro as measured by their ability to incorporate 14C glucose from tissue culture medium. Under these conditions the cultured ELS demonstrates an ability to synthesize HA. A theory of ELS function is proposed. PMID- 1415492 TI - Neural presbycusis: a diagnostic dilemma. AB - The combined term, sensorineural, is useful because clinical distinction between sensory and neural lesions is often difficult, and because sensory lesions may lead to secondary neural degeneration or, though rarely, a neural lesion may lead to secondary sensory degeneration. The threat of lawsuits for failure to identify treatable neurologic conditions has led to overuse of tests, while fiscal constraints exert pressure to limit expensive diagnostic testing. The purpose of this review of the relation between sensory and neural hearing loss is to provide a practical method to screen for neural lesions using pure-tone thresholds and a single speech discrimination score. The difference between the articulation index and the word recognition score of a patient provides a statistically reliable index of suspicion that may reduce the diagnostic dilemma of neural presbycusis. PMID- 1415491 TI - Sensory aids in conjunction with cochlear implants. AB - The use of cochlear implants in profoundly hearing-impaired individuals can restore varying degrees of auditory capabilities. Although very little auditory information is transmitted to these patients through amplification systems, we hypothesized that some of the cues obtained from sensory aids might be helpful when used in conjunction with the cochlear implant postoperatively. Eight patients implanted at NYU Medical Center, Bellevue Hospital Center, have used some sensory aid in addition to the Nucleus multichannel cochlear prosthesis. All subjects were evaluated using standard auditory tests including pure-tone and speech audiometry, portions of the Minimal Auditory Capabilities (MAC), Speech Pattern Contrast Perception (SPAC), Iowa test batteries; and the Early Speech Perception (ESP), Word Intelligibility by Picture Identification (WIPI), and Glendonald Auditory Screening Procedure (GASP), where appropriate. Subjects were evaluated under three conditions: implant alone, implant plus sensory aid, and sensory aid alone. Results indicate that the interaction between a multichannel cochlear implant and a sensory aid can provide some improved performance for adult implanted patients (i.e., they do better under the dual condition than in the implant-alone condition). Variables such as thresholds in the nonimplanted ear and usage time can affect the outcome. PMID- 1415493 TI - Unilateral acoustic neuromas in childhood without evidence of neurofibromatosis: case report and review of the literature. AB - A six-year-old female with a unilateral benign acoustic neuroma and no evidence of neurofibromatosis is presented. Review of the literature revealed only 16 cases of unilateral acoustic neuromas in children less than 15 years old. Children often do not appreciate hearing loss when compared with adults. As a result, they often present with larger tumors, thus adversely affecting outcome. The need for early diagnostic tests and a hearing-conservation surgical approach is emphasized. Routine follow-up imaging studies are crucial to rule out the development of a contralateral acoustic neuroma in neurofibromatosis-2 (NF-2). PMID- 1415494 TI - A new medication to control patulous eustachian tube disorders. AB - The disorder of hyperpatent eustachian tube is often unrecognized or misdiagnosed because of the ambiguous symptom of a "plugged ear." But when the patient also complains of autophony and/or hearing amphoric sounds, a patulous tube should be suspected. Persistent symptoms are distressing to most patients. This preliminary report evaluates a new nasal medication that produces closure of the tube and controls or eliminates these symptoms. It is demonstrated to be safe, predictable, and effective with little or no side effects. PMID- 1415495 TI - Retrolabyrinthine vestibular nerve section: evaluation of technical modification in 143 cases. AB - Selective vestibular nerve section is effective in relieving intractable vertigo while preserving hearing. Histologic study demonstrated overlap of the cochlear and vestibular fibers at the cochleovestibular cleavage plane within the posterior fossa. In the hopes of improving surgical results by sectioning these overlapping vestibular fibers, the technique of sectioning the vestibular division of the eighth nerve was modified to include a small portion of the cochlear division. We have evaluated 143 cases of retrolabyrinthine vestibular nerve section in which this technical modification was employed. A patient questionnaire was used to examine control of vertigo as well as changes in tinnitus, unsteadiness, and disability. Hearing preservation and incidence of complications were also reviewed. Resolution or improvement of vertigo occurred in 93 percent of Meniere's cases and 74 percent of non-Meniere's cases as compared to 97 percent and 68 percent, respectively, in the pre-1986 series. PMID- 1415496 TI - Traumatic perilymphatic fistula: how long can symptoms persist? A follow-up report. AB - In the past 18 years 68 ears (average 3.8 per year) were explored for perilymphatic fistula (PLF). A total of nine (13%) ears had a fistula identified at operation. Patients with a previous history of otologic surgery were excluded from this review. The most common etiology for PLF was head trauma (4 of 9). Most patients had persistent symptoms lasting months (average 6.7). Eighty-three percent of all patients had sudden or fluctuating hearing loss, 77 percent had vertigo or dysequilibrium, and 61 percent had tinnitus. Vertigo was the most commonly improved symptom postoperatively, and only 25 percent of patients had improved hearing. There were no major complications. The authors discuss indications for operation, criteria for diagnosis of PLF, and audiometric and electronystagmographic findings. This report agrees with other recent data indicating that exploration for fistula is an uncommon procedure performed by otologists. PMID- 1415497 TI - Relevance of the Tullio phenomenon in assessing perilymphatic leak in vertiginous patients. AB - The Tullio phenomenon was studied in 57 control subjects, in 7 patients with confirmed PLF and in 149 patients with different types of inner ear pathology. The subjects were exposed to low-frequency sound (LFS) with sound pressure levels ranging from 130 to 132 dB and at frequencies of 25, 50, and 63 Hz. The duration of each stimulation was 30 seconds. The postural responses were measured using a force platform and analyzed with a computer. In control subjects the LFS stimulation somewhat improved the postural stability. All patients with PLF showed significantly altered postural stability during LFS exposure. Also about 20 percent of patients with labyrinthine vertigo, patients with Meniere's disease, patients with chronic middle ear disease (with vertigo) had pathologic response to LFS. None of the patients with pure sensorineural hearing loss without vertigo responded to LFS. Post-urography with LFS loading is a new, promising tool in detection of PLF, but the specificity of the test is still unsatisfactory. PMID- 1415498 TI - Changes in hyaluronan synthesis by in vitro cultured endolymphatic sac cells. AB - The endolymphatic sac (ELS) has been implicated in the maintenance of endolymph volume and pressure in the membranous labyrinth through fluid resorption and secretion of osmotically active substances, known as glycosaminoglycans (GAGs). To assess whether the ELS cells synthesize the GAG, hyaluronan (HA), and to further elucidate the secretory function of the ELS, a series of experiments were carried out on in vitro tissue-cultured, fetal murine ELSs. In phase 1 of the investigation, the ELSs that were attached to a small portion of the posterior labyrinth, were resected from whole otocyst specimens and studied in tissue culture. This model was chosen to determine whether a change in endolymph homeostasis affects ELS activity. Radiolabeled 14C glucose incorporation was used to evaluate HA synthesis by ELS cells when cultured in vitro. Approximately 43 percent of the incorporated 14C glucose radiolabel was digested by Streptomyces hyaluronidase (an HA-specific hyaluronidase), suggesting HA synthesis by sac cells. In phase 2 of our experiments, the ELSs were not resected from the otocysts. Instead, they were left attached to intact membranous labyrinths, and whole otocysts were cultured. Studies analogous to those of phase 1, assessing the ability of the ELS cells to incorporate 14C glucose into HA, were performed on these specimens. Streptomyces hyaluronidase treatment of these ELS specimens resulted in a reduction in the removal of radiolabel. Therefore, the ELS cells of intact otocysts incorporated less 14C glucose into HA when compared to the ELS cells of the resected specimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415499 TI - Evaluation of cochlear function in a patient with "far-advanced" otosclerosis. AB - A patient with "far-advanced" otosclerosis with a profound bilateral hearing loss was evaluated for cochlear reserve using transtympanic electrocochleography (ECoG) and promontory stimulation. Results indicated that both ECoG and promontory responses were present, indicating that cochlear function was present bilaterally. A stapedectomy resulted in closure of the air-bone gap. Postoperative hearing yielded excellent aided responses compared to no measurable preoperative hearing aid benefit. This case serves to demonstrate the value of evaluating cochlear function using these electrophysiologic techniques. PMID- 1415500 TI - Facial nerve repair techniques in cerebellopontine angle tumor surgery. AB - This study reviewed the technique and outcome of facial nerve repair in cases of cerebellopontine angle (CPA) tumor that resulted in transection of the facial nerve. Between January 1982 and December 1989, the facial nerve was preserved in over 97.7 percent of 1110 cases of CPA tumor resection. Facial nerve repair was performed in 23 patients. The nerve repair was accomplished with either suture anastomosis or support with microfibrillar collagen. In the cases repaired with sutures, reanastomosis to a proximal facial nerve stump at the brain stem was performed with a single suture, while stabilizing the nerve with a fenestrated suction. Direct facial nerve neurorrhaphy or anastomosis with a greater auricular nerve interposition graft was successful in restoring tone and some degree of voluntary motion in 18 of the 21 patients with follow-up available (86%) and acceptable function (grade IV/VI or better) in 12 of 21 (57%). The degree of recovery of facial function was significantly better in patients without preoperative facial nerve symptoms and patients in whom the tumor did not arise from the facial nerve itself. We conclude that in cases of facial nerve transection in the CPA, good results are obtained by immediately reestablishing anatomic continuity of the nerve with direct reanastomosis or with a greater auricular nerve graft. PMID- 1415501 TI - Extended middle fossa and retrolabyrinthine approaches in acoustic neuroma surgery: case reports. AB - Hearing conservation surgery for small acoustic neuromas is well accepted. At present, two approaches are primarily used: the suboccipital and the middle fossa. The middle fossa approach to the internal auditory canal has the advantage of using bony landmarks to identify and protect the facial nerve. Because of anatomic constraints presented by the superior semicircular canal however, its uses are limited to intracanalicular tumors or tumors protruding only slightly into the cerebellopontine angle. By extending the approach through the superior semicircular canal, a wide access to the cerebellopontine angle can be safely obtained. In this study three procedures, two through the superior semicircular canal and one through the posterior semicircular canal, were utilized for hearing conservation surgery. By immediately sealing off the canal ends, hearing preservation was accomplished in two out of three of these cases. The dictum that labyrinthine opening invariably leads to anacusis should be reconsidered. By utilizing approaches through the semicircular canal, it is possible that morbidity from this surgery may be reduced. PMID- 1415502 TI - Transmission of change in the atmospheric pressure of the external ear to the perilymph. AB - In experiments using guinea pigs, the middle ear and perilymphatic pressures were simultaneously registered in response to pressure change in the external ear canal. In the first experiment, pressure was slowly loaded in the ear canal in the range of 200 mm H2O to -200 mm H2O. Pressure transmission to the perilymph was smaller when the bulla was open to the outside than when it was closed. It was significantly impaired by disruption of the ossicular chain and especially by closure of the round window. The data indicate that air volume in the middle ear cavity plays an important role in transmission of slowly changing atmospheric pressures. In the second experiment, the eustachian tube was closed and the pressure was changed in the range of 1000 mm H2O to -1000 mm H2O. The middle ear and perilymphatic pressures increased or decreased corresponding to the loading pressure in the range of 400 mm H2O and -200 mm H2O. Beyond these levels, response rate of the middle ear pressure decreased and perilymphatic pressure declined in spite of further increase in loading pressure. The increase in pressure difference between the middle ear and the inner ear might cause disruption of the round and/or oval windows. PMID- 1415503 TI - Meningeal carcinomatosis producing bilateral sudden hearing loss: a case report. AB - Meningeal carcinomatosis is characterized by diffuse infiltration of the leptomeninges by metastatic cancer in patients usually with a previous history of malignancy. Primary tumors are usually adenocarcinomas of the breast or lung, or malignant melanoma. Meningeal carcinomatosis can present with headache and/or a variety of cranial neuropathies. We report a case of meningeal carcinomatosis presenting as a complete, bilateral, sudden hearing loss without other cranial nerve findings--a previously unreported presentation. Our patient also exhibited an unusual primary tumor site (esophagus) and histopathology for meningeal carcinomatosis. The case was impressive for the subsequent abrupt onset of a series of cranial neuropathies and the rapid deterioration in the patient's condition. PMID- 1415504 TI - Facial nerve paralysis secondary to chronic otitis media without cholesteatoma. AB - Numerous papers have been written on facial nerve paralysis caused by chronic suppurative otitis media. However the authors found none documenting the results of therapy in a series of patients in whom facial nerve dysfunction was caused by chronic otitis media without cholesteatoma. Thus, there is little factual information available to help select a specific therapeutic plan for such cases. Over the past decade, the senior author has managed five cases (6 ears) of chronic suppurative otitis media without cholesteatoma in which facial paresis (4 ears) or paralysis (2 ears) developed 10 days or less before surgery. The chronic otitis media involved the mastoid and middle ear in five cases; and the mastoid, middle ear, and petrous apex in one case. Modified radical mastoidectomy was performed in four ears, tympanomastoidectomy with facial recess exposure in one ear, and complete mastoidectomy with middle cranial fossa petrous apicectomy in one ear. Five patients had complete recovery of facial nerve function (House grade I), and one patient had 90 percent recovery (House grade II). The results provide support for semi-emergent surgery in the management of chronic suppurative otitis media when facial nerve paralysis supervenes. PMID- 1415505 TI - Facial paralysis of pregnancy attributable to an arteriovenous steal syndrome. PMID- 1415506 TI - Vogue surgery. PMID- 1415507 TI - Prediction of auditory nerve survival in humans using the electrical auditory brainstem response. PMID- 1415508 TI - Comparison of apical and basal surfaces of confluent endothelial cells: patch clamp and viral studies. AB - The distribution of inwardly rectifying (Ki) and calcium-activated (KCa) potassium channels on the apical and basal surfaces of bovine aortic endothelial cells (BAECs) was examined by inverting BAEC monolayers onto polylysine-coated cover slips. To monitor cellular polarity, we examined human red blood cell adherence (hemadsorption) to the influenza virus protein, hemagglutinin (HA), and virus budding on the surface of infected BAECs. Hemadsorption and virus budding occurred on the apical surface but were not apparent on the basal surface of monolayers 1 and 5 h after inversion, although cellular HA antigen localization confirmed that all monolayers were infected. In contrast, by 9.5 and 24 h after inversion, hemadsorption was evident on the "new" apical surface. Single-channel patch-clamp analysis revealed the presence of both Ki and KCa channels on the apical surface and basal surface of BAEC monolayers 2-5 h after inversion. K channel conductance and kinetics were similar regardless of the surface monitored. This nonenzymatic mechanical technique of exposing the basal surface of endothelium provides a useful tool to study the distribution of ion channels in endothelium and in other polarized cell types grown in tissue culture. PMID- 1415509 TI - Volume-sensitive Ca influx and release from intracellular pools in gastric parietal cells. AB - The effects of osmotically induced changes in cell volume on cytoplasmic free Ca (Cai) were studied in parietal cells from intact rabbit gastric glands using digital image processing of fura-2 fluorescence. In resting unstimulated cells, Cai was unaffected by either cell swelling or shrinking when osmolarity was varied between 200 and 400 mosM (isotonicity 290 mosM). However, when cells were swelled in a 165 mosM solution (55% tonicity), a biphasic Ca increased was observed. On average, Cai increased transiently from 80 to 218 nM before stabilizing at approximately 140 nM. The peak was due to release from intracellular pools because it was present in Ca-free solutions while the sustained elevation was dependent on external Ca. In carbachol-stimulated cells, Ca influx was most sensitive to cell shrinkage. For example, addition of 25 mM sucrose (108% tonicity) caused a 30% decrease in the sustained carbachol stimulated Cai increase (plateau). In contrast, carbachol-stimulated cells were relatively insensitive to cell swelling, with a 30% decrease in tonicity causing only a 15% increase in the plateau. However, as in the unstimulated cells, extreme (55% tonicity) swelling caused additional increases in Cai levels. The carbachol-dependent effects of changes in cell volume on Cai could be mimicked by treating cells with thapsigargin, an inhibitor of Ca pumps of intracellular membranes that also has been shown to stimulate Ca entry. Thus, although extreme swelling conditions (55% tonicity) could elicit Cai increases in either the presence or absence of agonist, agonist was required to observe Cai decreases due to cell shrinkage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415511 TI - Evidence for the involvement of a K+ channel in isosmotic cell shrinking in vestibular dark cells. AB - Cell volume changes were measured in dark cells. Isosmotic addition of 21.4 mM K+, Rb+, Cs+, or NH4+ to a control solution containing 3.6 mM K+ caused piretanide-sensitive cell swelling (initial rate for K+, 0.100 +/- 0.005 microns/s; n = 119), suggesting dependence on the Na(+)-Cl(-)-K+ cotransporter. Subsequent isosmotic removal of 21.4 mM K+ caused piretanide-insensitive cell shrinking (initial rate, -0.104 +/- 0.005 microns/s; n = 119), which was inhibited by barium, lidocaine, quinidine, quinine, verapamil, and 4 aminopyridine but not tetraethylammonium (TEA) or glibenclamide, suggesting the involvement of K+ channel(s). Barium, lidocaine, quinine, quinidine, and 4 aminopyridine caused cell swelling in control solution (initial rate for barium, 0.011 +/- 0.004 microns/s; n = 6), suggesting that the K+ channel is also involved in efflux under control conditions. Cell shrinking was slowed by 21.4 mM extracellular K+, Rb+, or Cs+ but unaffected by Na+, Li+, TEA+, or NH4+ (all in the presence of piretanide and compared with N-methyl-D-glucamine), supporting the notion that the efflux mechanism is permeable to and/or inhibited by K+, Rb+, and Cs+. Cell shrinking was slowed by the presumed replacement of intracellular K+ by Cs+ but not by Rb+. Circumstantial evidence suggests that this putative K+ channel is present in the basolateral membrane. The physiological relevance of such a K+ channel might encompass regulatory volume decrease during K+ secretion. PMID- 1415510 TI - Regulation of oxygen consumption in fast- and slow-twitch muscle. AB - Phosphorus nuclear magnetic resonance spectra and steady-state O2 consumption rates were obtained from ex vivo arterially perfused cat biceps brachii (fast twitch) and soleus (slow twitch) muscles during and after periods of isometric twitch stimulation at 30 degrees C. In the biceps muscles, steady-state O2 consumption increased and phosphocreatine (PCr) concentration decreased progressively with stimulation. PCr recovery after these stimulation periods followed first-order kinetics with a half time of 10 min. The results in the biceps could be explained by a feedback control of cellular respiration by ADP concentration. In the soleus, steady-state O2 consumption also increased and PCr concentration decreased as stimulation rates increased. The half time for PCr recovery in the soleus was approximately 5 min, but, in contrast to the pattern in the biceps, the kinetics was not first order. There was an overshoot during the recovery period in the PCr content of soleus and a corresponding undershoot of Pi compared with resting values. Mitochondrial regulation by ADP is not sufficient to account for respiratory control in slow-twitch soleus. The respiration rate in neither muscle was dependent on the Pi content. Thus we conclude that the mechanism of control of cellular respiration is both quantitatively and qualitatively different in fast- and slow-twitch skeletal muscle. PMID- 1415512 TI - Ca2+ influx via Na(+)-Ca2+ exchange in immortalized aortic myocytes. I. Dependence on [Na+]i and inhibition by external Na+. AB - We have found that immortalized aortic myocytes have high Na(+)-Ca2+ exchange activity that is similar in amount to that of low-passage myocyte cultures. Replacing all external Na+ with K+ slightly increased 45Ca2+ uptake in cells with basal Na+ and greatly increased 45Ca2+ uptake in cells with increased intracellular Na+. External Na+ competitively inhibited 45Ca2+ uptake (inhibition constant approximately 10 mM). The dependence of exchange activity on intracellular Na+ was sigmoidal. The 50% maximum concentration (K0.5) for Na+ was 33 +/- 1 mmol/l cell water space. The Hill coefficient was 2.9 +/- 0.2, which is consistent with a stoichiometry of 3 Na+/1 Ca2+. Cytosolic free Na+ was estimated from the ratio of sodium-binding benzofuran isophthalate (SBFI) fluorescence and an in vivo calibration curve. Sulfinpyrazone, an inhibitor of anion transport, markedly increased the SBFI content of the cells without affecting cell Na+. Cytosolic free Na+ was 9 mM under basal conditions. Because free Na+ did not differ significantly from total Na+, little or no Na+ is bound or compartmentalized in these cells. The complete replacement of extracellular Na+ with K+ fails to evoke appreciable Ca2+ influx, at least in part, because of the low cell Na+ concentration relative to the K0.5 of the exchanger and its sigmoid dependence on Na+. PMID- 1415513 TI - Ca2+ influx via Na(+)-Ca2+ exchange in immortalized aortic myocytes. II. Feedback inhibition by [Ca2+]i. AB - Depolarization with 50 mM K+ evoked a spike in cytosolic free Ca2+ ([Ca2+]i) and increased 45Ca2+ uptake in immortalized aortic myocytes. The following evidence indicates that the electrogenic Na(+)-Ca2+ exchanger caused the Ca2+ influx that was evoked by K+ depolarization. First, K+ depolarization had no effect on [Ca2+]i and 45Ca2+ uptake in cells with basal Na+ but strikingly increased both in Na(+)-loaded cells. Second, the [Ca2+]i increases produced by K+ depolarization depended hyperbolically on external Ca2+ (50% maximum concentration = 1.5 mM). Third, the increases in [Ca2+]i and 45Ca2+ uptake were greater when external Na+ was replaced with K+ rather than with N-methyl-D glucamine or choline. A series of K+ depolarizations elicited a sequence of [Ca2+]i spikes, provided there was a short incubation at 5 mM K+ between the depolarizations. A prior K+ depolarization almost abolished the 45Ca2+ uptake response to K+ depolarization. The inhibition of exchange activity by a prior K+ depolarization required external Ca2+ and was completely reversible. A prior incubation with angiotensin II, platelet-derived growth factor, or ionomycin also inhibited exchange activity. Moderate [Ca2+]i increases probably feedback inhibit Ca2+ influx via the exchanger by a kinetic mechanism. Inactivation of the exchanger, together with Ca2+ extrusion or sequestration, causes the rapid decrease in [Ca2+]i from the peak evoked by depolarization. PMID- 1415514 TI - Contractile arrest accelerates myosin heavy chain degradation in neonatal rat heart cells. AB - Mechanical forces influence the growth and metabolism of a variety of cells, including cultured neonatal rat ventricular myocytes. To determine whether mechanical activity affected the synthesis and turnover of myosin heavy chain (MHC) in these striated muscle cells, MHC fractional degradative rates were measured in spontaneously beating cells and in arrested myocytes in which contractile activity was prevented by L-channel blockade (with verapamil, nifedipine, nisoldipine, and diltiazem) or K+ depolarization. MHC degradative rates were measured as the difference between rates of MHC synthesis and accumulation and in pulse-chase biosynthetic labeling experiments. Both methods indicated that contractile arrest markedly increased MHC degradation. Contractile arrest produced by L-channel blockade accelerated MHC degradation to a greater extent than K+ depolarization. The signal transduction pathway linking contractile activity to alterations in MHC degradation did not involve protein kinase C (PKC), because MHC degradation was unaffected by activating PKC in arrested cells or inhibiting PKC in spontaneously beating cells. Chloroquine and E-64 did not suppress the accelerated MHC degradation, suggesting that the rate limiting step in MHC turnover occurred before degradative processing by cellular proteinases. Using a computer simulation, we hypothesize that the rate-limiting step in MHC turnover preceded (or was coincident with) MHC release from thick filaments. Thus mechanical forces may influence MHC half-life by regulating the rate of myosin disassembly. PMID- 1415515 TI - Effects of fat availability on acetyl-CoA and acetylcarnitine metabolism in rat skeletal muscle. AB - This study was designed to examine the effects of stimulation and fat availability on the contents of acetyl coenzyme A (acetyl-CoA), free CoA (CoASH), acetylcarnitine, and free carnitine in the oxidative fiber types of rat skeletal muscle. Hindlimb muscles were perfused with no exogenous free fatty acids (FFA) or high FFA (0.93 +/- 0.03 mM) for 10 min at rest and during isometric, tetanic stimulation. Soleus (SOL) and red gastrocnemius (RG) muscles were sampled prior to perfusion and following rest perfusion and 1 and 5 min of stimulation. The SOL muscle contains predominantly slow oxidative (SO) fibers and the RG contains 56% fast oxidative-glycolytic (FOG) and 35% SO fibers. O2 uptake and tetanic tension production were similar in the fat-free and high FFA treatments. Rest perfusion with high FFA increased acetyl-CoA from 14.6 +/- 1.0 to 20.1 +/- 2.5 nmol/g dry muscle (dm) and acetylcarnitine from 0.12 +/- 0.01 to 0.78 +/- 0.18 mumol/g dm in the RG, while fat-free perfusion had no effect. The SOL results were similar as high FFA increased acetyl-CoA from 7.7 +/- 1.0 to 14.2 +/- 3.1 nmol/g dm and acetylcarnitine from 0.14 +/- 0.02 to 0.49 +/- 0.09 mumol/g dm. Stimulation increased acetyl-CoA and acetylcarnitine to values above rest in SOL and RG in both treatments and removed all fat-free and high-fat differences. The decreases in CoASH and free carnitine were reciprocal to the increases in acetyl-CoA and acetylcarnitine at all time points in both muscles such that total CoA and carnitine were constant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415516 TI - Volume-sensitive basolateral K+ channels in HT-29/B6 cells: block by lidocaine, quinidine, NPPB, and Ba2+. AB - Volume-sensitive basolateral K+ channels were studied in apically amphotericin B permeabilized HT-29/B6 monolayers in Ussing chambers with current fluctuation analysis. The basolateral K+ conductance and Lorentzian K+ channel noise were osmotically activated in presence of Cl- concentrations greater than or equal to 74 mM. Under isotonic conditions with 148 mM Cl-, a large transepithelial K+ current of 500 +/- 16.8 microA/cm2 and a spontaneous Lorentzian K+ channel noise with a corner frequency of 29.8 +/- 1.6 Hz (n = 31) were observed. Increasing extracellular osmolalities by addition of sucrose sensitively decreased the K+ current across the basolateral membrane. Half-maximal sucrose concentration was 20 +/- 6 mM for this shrinkage maneuver. The osmotically sensitive K+ pathway was similarly activated with the halide Br- and selective for K+ over Rb+ (4:1). The established K+ channel blockers lidocaine [50% inhibitory concentration (IC50) = 49.0 +/- 3.7 microM], quinidine (IC50 = 10.1 +/- 1.3 microM), and also the chloride channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (IC50 = 114 +/- 2.1 microM) completely inhibited basolateral K+ currents, whereas 46% of K+ current was blocked by barium (IC50 = 95.3 +/- 23.2 microM). Osmotic sensitivity of this K+ conductance made a correction for hypertonic effects of added blockers necessary, and considerable osmotic effects of blockers at commonly used doses were shown. All blockers induced dose dependently additional Lorentzian noise, indicating a direct inhibitory action on basolateral K+ channels. In this human Cl- secretory cell line, volume-sensitive K+ channels are localized only in the basolateral membrane and may modulate osmotic regulation when HT-29 cells swell. PMID- 1415517 TI - Phospholipid metabolism and intracellular Ca2+ homeostasis in cultured rat hepatocytes intoxicated with cyanide. AB - The killing of cultured hepatocytes by 1 mM sodium cyanide was reduced by 100 microM chlorpromazine or cytochalasin B (25 micrograms/ml) or by lowering the pH of the culture medium to 6.0. In each case, ATP was depleted despite the decreased number of dead cells. The cell killing by cyanide was accompanied by an accelerated release of 3H-labeled arachidonate from phospholipids. Depletion of ATP by oligomycin did not accelerate phospholipid degradation or kill the hepatocytes. Chlorpromazine, cytochalasin B, and extracellular acidosis reduced the rate of phospholipid degradation in control cells as well as the increase that occurred with cyanide. The calcium ionophore A23187 increased phospholipid degradation and killed the hepatocytes. Chlorpromazine and extracellular acidosis, but not cytochalasin B, protected the cells and prevented the increased lipid degradation in response to A23187. After addition of cyanide, cytosolic free calcium ([Ca2+]i) did not change for 71 +/- 8 min, at which time it rose to a plateau of 683 +/- 210 nM within 10 min. A second and larger rise occurred after 84 +/- 8 min and before the death of the cells at 89 +/- 8 min. Treatment with 3.5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, as well as removal of extracellular calcium, prevented these late increases in [Ca2+]i without affecting the loss of viability. It is concluded that cyanide kills cultured hepatocytes by a mechanisms that is likely related to an accelerated degradation of phospholipids. This change in lipid metabolism is not mediated by a rise in [Ca2+]i but rather may relate to an alteration in the interaction between the cytoskeleton and the plasma membrane. PMID- 1415518 TI - Ionic basis for spontaneous depolarizations in isolated smooth muscle cells of canine colon. AB - The type of cell that serves as the pacemaker in the colon is presently unknown. This study evaluated the ionic basis of spontaneous depolarizations in circular smooth muscle cells isolated from canine colon using whole cell voltage and current clamp techniques. Increasing temperature increased the probability of observing spontaneous depolarizations, depolarized the resting membrane potential (RMP), and increased Ca2+ and K+ currents. Spontaneous depolarizations occurred as rhythmic events, in bursts, or as isolated events. Varying the holding potential from -100 to -40 mV inhibited a component of inward current thought to be necessary for spontaneous depolarizations. The Ca2+ channel blockers, nickel and nisoldipine, inhibited spontaneous depolarizations. Nickel caused a hyperpolarization, whereas nisoldipine did not affect RMP. Ouabain depolarized the RMP and inhibited spontaneous depolarizations. The K+ channel blocker, tetraethylammonium, depolarized the RMP and lengthened the duration of spontaneous depolarizations. The key finding is that single colon circular smooth muscle cells are capable of generating spontaneous depolarizations similar to those described for slow waves in intact tissues and that a temperature- and nickel-sensitive inward current is essential for spontaneous activity. PMID- 1415519 TI - A novel remote-sensing isometric force transducer for micromechanics studies. AB - We have developed an innovative transducer for measuring force with femtonewton to-micronewton resolution in biological systems. A magnetic microsphere is attached to the specimen being studied and is positioned between two electromagnets. Video microscopy and edge detection are used to monitor small movements of the microsphere that occur when the specimen generates force. An automatic control system adjusts the current through the electromagnets to keep the microsphere stationary. Measured force is a linear function of this current. This transducer is unique in its combination of sensitivity and isometric properties and its ability to measure force without direct connections to the specimen. That is, the transducer is "remote sensing" and can measure force through intervening membrane or tissue. The transducer is isometric at steady state to the limit at which displacement of the microsphere can be resolved, which can be as low as 19 nm. The completed system is being used to study the mechanics of interstitial connective tissue but may also be used to study molecular generation of force. PMID- 1415521 TI - Effects of thyroid hormones on urinary and renal kallikreins. AB - The effects of thyroid hormones on the urinary excretion of kallikrein and on renal kallikrein were studied in rats. Total and active urinary kallikrein was decreased after thyroidectomy, but renal kallikrein content remained unchanged. Diuresis increased, and kidney weight and plasma aldosterone concentration decreased. Treatment with 3,5,3'-triiodo-L-thyronine restored the urinary kallikrein in thyroidectomized rats to normal and increased it in intact rats. It also produced increases in kidney weight and plasma aldosterone and a decrease in diuresis. The effect of thyroid hormones on the urinary kallikrein response to mineralocorticoids was also tested. Deoxycorticosterone acetate increased urinary kallikrein more in normal than in thyroidectomized rats. These results suggest that thyroidectomy decreases renal kallikrein synthesis and lowers the turnover rate of the enzyme, changes not detectable by a single measurement of the renal kallikrein content but reflected by an alteration in the urinary excretion of the enzyme. Thyroid hormones participate in the control of urinary kallikrein. This effect, however, is probably indirect and may be mediated by mineralocorticoids since thyroid function affects both the plasma level of aldosterone, which is known to influence renal kallikrein, and the kallikrein response to exogenous mineralocorticoids. PMID- 1415520 TI - Ca(2+)-independent isoforms of protein kinase C differentially translocate in smooth muscle. AB - It is generally assumed that smooth muscle contraction is dependent on changes in intracellular Ca2+ concentration ([Ca2+]i); however, we have previously reported that alpha-agonist-induced contraction of aorta smooth muscle cells can occur in the absence of changes in [Ca2+]i [Collins, E. M., M. P. Walsh, and K. G. Morgan. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H754-H762, 1992]. The mechanism of this [Ca2+]i-independent contraction is controversial. We have now identified the Ca(2+)-independent protein kinase C (PKC) isoforms epsilon and zeta in ferret aorta and have used digital imaging microscopy to determine their subcellular distribution. At rest, epsilon-PKC is diffusely distributed in the cytosol, whereas zeta-PKC is concentrated in the perinuclear region; both isoforms are excluded from the nuclear space. Agonist stimulation causes a [Ca2+]i-independent translocation of epsilon-PKC to the surface membrane and of zeta-PKC to the intranuclear compartment. In comparison, ferret portal vein cells, which display a totally Ca(2+)-dependent agonist contraction, are lacking in epsilon-PKC but display perinuclear zeta-PKC, which translocates intranuclearly on activation. Thus the Ca(2+)-independent vascular contraction appears to be associated with plasmalemmal translocation of epsilon-PKC; in contrast, the intranuclear translocation of zeta-PKC may function in control of gene expression. PMID- 1415522 TI - Plasma GSH/GSSG affects glucose homeostasis in healthy subjects and non-insulin dependent diabetics. AB - In healthy subjects (n = 10) and non-insulin-dependent (type II) diabetics (n = 10) matched for age [43.1 +/- 2.2 vs. 41 +/- 4.4 yr, P = not significant (NS)], body mass index (25.1 +/- 1.1 vs. 26 +/- 0.8 kg/m2, P = NS), gender ratio [5 males (M)/5 females (F) vs. 5M/5F], and mean arterial blood pressure (105 +/- 7 vs. 106 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after glutathione infusion (15 mg/min) and the relative increase in the plasma reduced (GSH)/oxidized (GSSG) glutathione ratio. The rise in the plasma GSH/GSSG ratio significantly improved total body glucose disposal in healthy subjects and in diabetic patients. In this latter group, GSH infusion potentiated the beta-cell response to glucose slightly. In controls and diabetics, insulin infusion with a simultaneous increase in the plasma GSH/GSSG ratio significantly enhanced nonoxidative glucose disposal without affecting oxidative glucose metabolism. After glutathione infusion, all metabolic and hormonal changes correlated with a significant decline in plasma membrane microviscosity. In conclusion, the plasma GSH/GSSG ratio seems to play a major role in the modulation of glucose homeostasis mainly in diabetics. PMID- 1415523 TI - Thermogenesis after surgery: effect of perioperative heat conservation and epidural anesthesia. AB - Body temperature, respiratory gas exchange, and plasma catecholamines were determined before and after surgery in three groups [control (C), warmed (W), and epidural (E) who received local anesthetic at T4-S5 dermatomes during and for 24 h after surgery] of patients undergoing colonic surgery under general anesthesia. At the end of surgery, group W were nursed in an ambient temperature of 28-30 degrees C, whereas the others were at 20-23 degrees C for a period of 24 h. Core (Tc) and dorsal hand temperature decreased during surgery in both C and E (P less than 0.05) but not in W. After surgery, Tc increased similarly in C and E and by a smaller amount in W. Plasma catecholamine concentrations increased significantly in C and W but not in E (P less than 0.001), with the greatest response occurring in C. Postoperative oxygen consumption and carbon dioxide production exceeded preoperative values (P less than 0.01) in C but not in W or E. After surgery, plasma albumin fell and C-reactive protein increased similarly in all three groups. Thus body heat conservation or epidural blockade attenuates or abolishes the rise in plasma catecholamines and oxygen consumption postoperatively but does not prevent the increase in Tc or the acute phase protein response. PMID- 1415524 TI - Energy metabolism and aging: a lifelong study of Fischer 344 rats. AB - Metabolic rate is widely regarded as an important component of aging processes, but variation of metabolic rate with age has not been well characterized. The purpose of the present study was to measure daily metabolic rate under usual living conditions over the lifespan of barrier-maintained Fischer 344 rats. In addition, effects of life-prolonging food restriction were assessed. Metabolic rate was measured indirectly by analysis of gas entering and leaving standard rodent cages over a 24-h period. Group A rats were fed ad libitum. Group B rats were fed 60% of ad libitum intake from 6 wk of age. Both group A and group B rats exhibited variation of metabolic rate per unit lean mass over the lifespan, with metabolic rate decreasing from 6 to 18 mo and then increasing from 18 to 24 mo of age. Results show estimates of lifetime energy expenditure in rats should take account of variability of metabolic rate and confirm the life-prolonging action of food restriction is not a consequence of reduced metabolic rate per unit metabolic mass. Rather, restricted rats are able to sustain appropriate fluxes of nutrients and appropriate metabolic rate under conditions of fuel utilization which promote maintenance of cellular homeostasis. PMID- 1415525 TI - Stimulation of protein synthesis in pig skeletal muscle by infusion of amino acids during constant insulin availability. AB - Incorporation of L-[1-13C]leucine into muscle protein and leg exchange of L [15N]phenylalanine were used to assess the effects over 240 min of amino acid supply on leg protein turnover in anesthetized, overnight-fasted (Landrace x Great White) female pigs. In all pigs, plasma insulin and glucagon stability was ensured by infusion of somatostatin (8 micrograms.kg-1.h-1), insulin (6 mU.kg-1.h 1), and glucagon (72 ng.kg-1.h-1). Mixed amino acid infusion (260 mg.kg-1.h-1) caused a 2- to 2.5-fold elevation of arterial plasma phenylalanine and leucine; in a control group (no amino acid infusion), an increase in phenylalanine and leucine concentration was observed as a result of the hormone clamp. Plasma insulin and glucagon concentrations were steady and not significantly different between control and amino acid-infused groups during the final 240 min, but plasma glucose fell (P less than 0.05) in both groups (4.57 +/- 0.17 to 3.15 +/- 0.73 mM). Muscle protein synthetic rate (estimated from the change in L-[1 13C]leucine incorporation compared with labeling of [13C]leucyl-tRNA) was greater in amino acid-infused (0.076%/h) than in control (0.053%/h) pigs. In the control group, leg amino acid balance was negative (Phe alone, -10.2 +/- 9.4 nmol Phe.100 g-1.min-1; total amino acids, -0.27 +/- 1.04 micrograms amino N.100 g-1.min-1), but during amino acid infusion, balance was positive (Phe alone, +33.6 +/- 8.8 nmol Phe.100 g-1.min-1; total amino acids, +58.2 +/- 4.9 micrograms amino N.100 g 1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415526 TI - Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response. AB - Besides exerting its own lipolytic effect, growth hormone (GH) has been reported to potentiate the lipolytic response of adipose tissue to epinephrine. It was thought interesting to find out whether long-term recombinant human growth hormone (rhGH) administration modifies epinephrine-induced lipolysis in isolated adipocytes of GH-deficient adults. In a double-blind protocol, GH-deficient subjects received either 6 mo placebo (controls, n = 5) or 6 mo rhGH (treated, n = 5). Biopsies of fat were obtained from the periumbilical region before and after placebo or rhGH administration. The response of the collagenase-isolated fat cells to various concentrations of epinephrine was assessed by glycerol release, measured by bioluminescence. Epinephrine-induced lipolysis was not altered by 6 mo placebo, while it was significantly increased by 6 mo rhGH. A similar response was obtained with isoproterenol, but no significant differences occurred in either group with UK 14304, an alpha 2-adrenoreceptor agonist. Thus, in GH-deficient adults, long-term rhGH administration improves the lipolytic response of isolated adipocytes to epinephrine, essentially by increasing the efficiency of the beta-adrenergic pathway. PMID- 1415527 TI - Uptake of glucose carbon in muscle glycogen and adipose tissue triglycerides in vivo in humans. AB - Glucose disposal into muscle glycogen has previously been directly studied after intravenous, but not after physiological, oral administration. In this study 100 g glucose, containing 50 microCi [U-14C]glucose, were taken orally by premenopausal women in the overnight fasting state or after a carbohydrate-rich meal. After 4 h, biopsies were taken from the vastus lateralis muscle and abdominal and femoral subcutaneous adipose tissue for determinations of label in isolated glycogen and triglycerides, respectively. Uptake of administered glucose carbon in muscle glycogen was estimated to be approximately 20 g in the fasting and approximately 9 g in the carbohydrate-fed groups, respectively. Total uptake in adipose tissue triglycerides was approximately 2 g. Glucose carbon uptake in muscle glycogen correlated positively with glucose infusion rates during euglycemic hyperinsulinemic glucose clamps, glycogen synthase activity in vitro, and type I muscle fiber distribution and fiber area. Negative correlations were found between glucose uptake in adipose tissue triglycerides, type II fiber distribution and fiber area, as well as the waist-to-hip circumference ratio and degree of obesity. It was concluded that muscle glycogen is probably not a major pathway for disposal of oral glucose carbon in the sedentary condition. PMID- 1415528 TI - Dexamethasone acts locally to inhibit longitudinal bone growth in rabbits. AB - Excess glucocorticoid is a potent inhibitor of epiphysial growth. Several mechanisms have been suggested to explain this growth inhibition, including both direct local effects of glucocorticoid on the epiphysial growth plate and indirect systemic effects. Previous studies do not distinguish which of these proposed mechanisms is actually responsible for the growth suppression in vivo. To resolve this controversy, we developed a method for delivering glucocorticoid directly into the rabbit epiphysial growth plate and for accurately measuring the resulting epiphysial growth rate. Five-week-old male rabbits received a local infusion of dexamethasone phosphate (80 ng/microliters, 1 microliters/h) into one proximal tibial growth plate and an infusion of vehicle into the contralateral growth plate. Growth rate was determined by inserting metal pins into the bone immediately adjacent to the growth plate and measuring the change in distance between pins on serial radiographs. This method permitted growth rates to be measured over intervals as short as 3 days, with an error of approximately 5%. Local dexamethasone administration decreased proximal tibial growth rate by 77% compared with the contralateral vehicle-treated tibia (P less than 0.0001). We conclude that excess glucocorticoid causes a rapid potent inhibition of growth by a direct local action on the growth plate. PMID- 1415529 TI - On the mechanism of stimulation of ureagenesis by gluconeogenic substrates: role of pyruvate carboxylase. AB - Gluconeogenic substrates, lactate or pyruvate, or ornithine produced 100% increase of urea synthesis from NH4Cl. The combined administration of ornithine and lactate (or pyruvate) produced more than additive effects, indicating that they acted at different steps in a potentiating manner. The uptake of ornithine was enhanced by gluconeogenic substrates. This finding may explain, at least in part, the stimulating effect of these substrates on ureagenesis from NH4Cl and ornithine. The gluconeogenic substrate-induced stimulation of ureagenesis from NH4Cl was still observed under conditions of reduced flux through pyruvate carboxylase, ruling out that their action was exclusively mediated by the anaplerotic effect of this enzyme. Pyruvate was a more potent stimulator of ureagenesis than lactate and its effect less sensitive to pyruvate carboxylase inhibition. These observations indicate that a correlation exists between stimulation of ureagenesis by gluconeogenic substrates and flux through pyruvate dehydrogenase. It is concluded that gluconeogenic substrates may stimulate ureagenesis from NH4Cl by 1) increasing intracellular ornithine availability and/or 2) enhancing flux through pyruvate dehydrogenase and consequently the tricarboxylic acid cycle activity. PMID- 1415530 TI - Regulation of expression of the lipoprotein lipase gene in brown adipose tissue. AB - The regulation of lipoprotein lipase gene expression in brown adipose tissue was studied. Rats were preacclimated to 21 degrees C. Exposure to cold (4 degrees C) resulted in a rapid increase in the level of lipoprotein lipase mRNA in the tissue. The level peaked (expressed per microgram total RNA) after approximately 8 h and then slowly declined. The increased lipoprotein lipase mRNA level was not due to an increased stability of the mRNA, but, in a transition event from a high to a low expression of the lipoprotein lipase gene, a transcription-dependent process was recruited that accelerated the breakdown of lipoprotein lipase mRNA. Norepinephrine injections increased lipoprotein lipase mRNA levels in the tissue; this effect was mediated via a beta-adrenergic receptor. The effect of cold could be mimicked by norepinephrine injections, and these two effects were not additive, indicating that the cold effect was mediated by norepinephrine. The lipoprotein lipase mRNA level was also increased by insulin injections (into fasted animals); thus an increase in lipoprotein lipase gene expression in brown adipose tissue may be induced via two different stimuli, which, intracellularly, would be mediated via different signaling systems. In all investigated conditions, the changes in lipoprotein lipase mRNA levels observed here were parallelled by alterations in lipoprotein lipase activity reported earlier from this laboratory. It was therefore concluded that, under the conditions studied, lipoprotein lipase activity in brown adipose tissue was primarily regulated at the transcriptional level. PMID- 1415531 TI - Evidence for the modulation of cell calcium by epinephrine in fish hepatocytes. AB - The effect of epinephrine (10(-7) M) on cytosolic free-Ca2+ concentration ([Ca2+]i) and its dependency on external Ca2+ were studied in fura-2-loaded hepatocytes isolated from three teleost fish species: American eel, brown bullhead, and rainbow trout. Basal [Ca2+]i was similar in eel and trout hepatocytes (79.6 +/- 14.6 and 75.7 +/- 17.4 nM, respectively) but was significantly higher in bullhead cells (184 +/- 23 nM). Epinephrine-induced [Ca2+]i oscillations were observed only in eel hepatocytes. These oscillations, which presented variable patterns among individual cells, also developed in the absence of external Ca2+, although their amplitude progressively declined to eventually vanish under such conditions. In bullhead hepatocytes, epinephrine induced a biphasic [Ca2+]i response, with an initial transient rise followed by a sustained component; this response was virtually abolished in the absence of extracellular Ca2+. The peak [Ca2+]i achieved (433.5 +/- 135.6 nM) was more than two times that of eel cells (184.3 +/- 30 nM) but represented a similar percent increase above control [Ca2+]i for both species. Rainbow trout hepatocytes, contrary to eel and bullhead cells, demonstrated little epinephrine sensitivity, with less than 20% of the cells responding. These data clearly point to significant species differences both in terms of epinephrine-induced changes in [Ca2+]i and in the dependence of these transients on external Ca2+. Thus the eel response relies primarily on intracellular stores, whereas the bullhead response principally involves enhanced influx of Ca2+ from the extracellular milieu. Furthermore, the similarity of these responses with those reported for mammalian hepatocytes strongly suggests that an alpha-adrenoceptor/Ca2+ transduction system is involved in at least eel and bullhead hepatocytes. PMID- 1415532 TI - Vasoconstrictor-induced secretion of ANP in fetal sheep. AB - Fetal secretion of atrial natriuretic peptide (ANP) increases during volume expansion and hypoxia. It is unknown whether this is associated with alterations in right atrial pressure (RAP) or distension and whether increases in ANP secretion reflect effects of specific vasopressors. To address this we studied fetal sheep (n = 13) at 125-140 days gestation, infusing either angiotensin II (ANG II; 0.023-5.73 micrograms/min) or the alpha-agonist phenylephrine (Phen; 0.031-7.64 micrograms/min) while monitoring mean arterial pressure (MAP), RAP, heart rate, and amniotic sac pressure. Arterial blood was obtained before and at 5 min of infusion to measure ANP, blood gases, and pH; umbilical venous blood was collected to determine placental clearance of ANP. ANG II caused dose-dependent increases in MAP and plasma ANP (P less than 0.05), whereas Phen caused dose dependent increases in MAP, but ANP rose only with the highest dose (40 +/- 12%). delta MAP and delta RAP were highly correlated for Phen (r = 0.74, P = 0.002) and ANG II (r = 0.90, P less than 0.001), but for both agents the increase in delta RAP was proportionately greater than delta MAP, and increases in plasma ANP were greater per millimeter mercury rise in RAP than that observed with MAP. Increases in ANP were associated with a dose-dependent rise in hematocrit, suggesting decreases in intravascular volume. There was no fetal placental clearance of ANP. As in adults, ANG II- and alpha-agonist-induced fetal ANP secretion appears to primarily reflect increases in RAP and thus right atrial distension. PMID- 1415533 TI - Thyroid hormone effects on cardiac gene expression independent of cardiac growth and protein synthesis. AB - Prior studies have demonstrated the importance of hemodynamic loading in mediating thyroxine (T4)-induced cardiac hypertrophy. Direct cellular effects of thyroid hormone have been implicated in modulating the expression of the myosin heavy chain (MHC) genes and the slow sarcoplasmic reticulum calcium adenosine triphosphatase (SR Ca(2+)-ATPase) gene. In the present report, administration of T4 for 72 h did not stimulate growth of the hemodynamically unloaded heterotopic isograft. The synthetic rates of total cardiac proteins and MHC in the isograft remained significantly lower at 64 and 53% of the respective rates measured simultaneously in the in situ working heart. Although total left ventricle RNA content in the isograft was unchanged by T4, alpha-MHC and SR Ca(2+)-ATPase mRNA concentrations were increased 181 and 208%, respectively, and the previously observed beta-MHC expression was completely prevented. These data indicate that, although T4 requires an increased hemodynamic load to stimulate cardiac protein synthesis, it is capable of directly altering the expression of at least two myocyte-specific genes. Therefore some of the phenotypic alterations observed with thyroid hormone treatment are the result of direct effects of the hormones on specific cardiac genes and independent of changes in cardiac growth. PMID- 1415534 TI - Importance of basal glucagon in maintaining hepatic glucose production during a prolonged fast in conscious dogs. AB - We undertook studies in conscious dogs to assess the role of basal glucagon in stimulating glucose production after a 7-day fast. Two protocols consisting of a 40-min basal period (-40 to 0 min), and a 180-min test period (0-180 min) were used. During the test period of the first protocol (hormone replacement; n = 4), somatostatin was infused (0.8 micrograms.kg-1.min-1) along with basal intraportal replacement amounts of insulin and glucagon, whereas in the second protocol (glucagon deficiency; n = 5), somatostatin plus insulin alone were infused. Glucose production and gluconeogenesis were measured using tracer and arteriovenous difference techniques. Plasma insulin levels were similar during the test period in both protocols (6 +/- 1 microU/ml). The plasma immunoreactive glucagon level in the control protocol averaged 50 +/- 8 pg/ml, whereas in the glucagon-deficiency protocol the level fell from 50 +/- 8 to 29 +/- 8 pg/ml (P less than 0.05). The plasma glucose level and the rate of glucose production were unchanged during bihormonal replacement. During glucagon deficiency the plasma glucose level was held constant at 100 +/- 4 mg/dl by glucose infusion. Tracer determined endogenous glucose production fell from 1.8 +/- 0.1 to 1.0 +/- 0.1 mg.kg-1.min-1 by 30 min (P less than 0.05). After 3 h of glucagon deficiency, gluconeogenic conversion of alanine to glucagon was reduced 40% and the hepatic fractional extraction of alanine was reduced by 45%. The efficiency of the gluconeogenic process within the liver was not altered by glucagon deficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415535 TI - Interactions between insulin and glucocorticoids in the maintenance of genetic obesity. AB - Glucoregulation and body composition were examined in 3-mo-old C57BL/6 ob/ob mice 6 wk after streptozotocin (STZ) or STZ plus adrenalectomy. STZ depressed somatic growth in ob/ob mice but did not cause hyperglycemia until immunoreactive insulin (IRI) was 40% (100 microU/ml) that of intact ob/ob mice. When IRI approached that of lean mice (40 microU/ml), ob/ob mice displayed severe hyperglycemia (800+ mg/dl) and other sequelae of type I diabetes but still maintained the same 50% body fat as untreated obese mice. In contrast, STZ diabetes in lean mice caused disproportionate reductions in body fat. Adrenalectomy before STZ led to the same insulinopenia, depressed growth, and hyperglycemia as STZ alone, but, after combined treatment, percent body fat declined in proportion to IRI. Thus a subgroup of severely diabetic adrenalectomized STZ obese mice with very low IRI (20 microU/ml) had body fat contents and fat-free masses equal to those of weight matched lean mice. The data suggest that hypercorticoidism rather than hyperinsulinemia is largely responsible for obesity in ob/ob mice. However, in the absence of adrenal glucocorticoids, or perhaps with just their normalization, hyperinsulinemia appears necessary for maintaining excessive body energy stores. PMID- 1415536 TI - Fasting and lactate unmask insulin responsiveness in the isolated working rat heart. AB - We have previously reported that the nutritional state in vivo results in differential insulin responses by the perfused heart in vitro. To further assess the effects of insulin on glucose uptake at physiological work loads, hearts from fed and fasted (16-20 h) rats were perfused with buffer containing 2-[18F]fluoro 2-deoxy-D-glucose (2-FDG) and glucose (10 mM) alone or plus lactate (10 mM) as a competing substrate, with insulin (10 mU/ml) added after a control period. When glucose was the only substrate, the addition of insulin decreased the fractional rate of 2-FDG uptake in hearts from either fed or fasted rats. The effect of insulin on increasing myocardial 2-FDG uptake was immediate and sustained only in hearts from fasted rats in the presence of lactate, despite no change in cardiac work. At the same time, the increase in 2-FDG uptake and phosphorylation was associated with an increase in the tissue content of glycogen in hearts from fasted rats. We conclude that lactate unmasks insulin sensitivity in heart muscle at physiological work loads but that this unmasking of insulin-mediated glucose uptake is dependent on the nutritional state of the animal. The glucose up as a result of insulin stimulation is preferentially utilized for glycogen repletion and does not enter the glycolytic pathway. This observation also suggests that myocardial glycogen synthesis in vitro is affected by the nutritional state in vivo and that lactate provides a substrate for oxidative phosphorylation while glucose is preferentially utilized for glycogen synthesis. PMID- 1415538 TI - Plasma carnitine in fasting neonatal and adult northern elephant seals. AB - Maintenance of adequate body carnitine stores is a requisite for fasting mammals, whose energy is derived mainly from free fatty acid oxidation. The impact of longterm fasting on carnitine status is unclear, and there have been no reports of carnitine during naturally occurring fasts. Total (TC), free (FC), and acylated (AC) plasma carnitine levels were determined in 10 weaned and 11 adult northern elephant seals (Mirounga angustirostris) during natural fasts lasting from 1 to 3 mo. In pups, TC declined little and AC increased only slightly [P greater than 0.05, analysis of variance (ANOVA)] through 11 wk of fasting. Plasma FC dropped by 53 and 26% from week 1 values at 10 and 11 wk fasting, respectively (P = 0.014, ANOVA). The AC/FC ratio did not approach 1.0 until 7 wk of fasting. TC was 38.6 +/- 1.4 microM and 47.6 +/- 4.1 microM in adult females and males, respectively. Adult AC/FC ratios were 0.71 +/- 0.10 (females) and 0.08 +/- 0.04 (males). Plasma TC status is not negatively affected by extended fasting in adult and weaned northern elephant seals. These data support the hypothesis that fasting northern elephant seals defend plasma TC and maintain an attenuated AC/FC ratio well into their prolonged natural fast. PMID- 1415537 TI - Pretranslational regulation of two cardiac glucose transporters in rats exposed to hypobaric hypoxia. AB - To investigate the mechanism by which cardiac glucose utilization increases during hypoxia and increased work load, we studied the effect of 2 and 14 days of hypobaric hypoxia on the expression of two subtypes of the facilitative D-glucose transporter, the GLUT-4 or "insulin-regulatable" isoform and the GLUT-1 isoform thought to mediate basal transport. Rats lose weight when exposed to hypobaric hypoxia, so fasting controls were used in the 2-day studies and pair-fed controls in the 14-day experiments. Hypobaric hypoxia (PO2 69 mmHg) resulted in right ventricular (RV), but not left ventricular (LV), hypertrophy. RV and LV GLUT-1 mRNA levels increased 2- to 3-fold after 2 days and 1.5- to 2-fold after 14 days of hypobaric hypoxia compared with both fasted rats and normal controls. RV GLUT 1 protein increased approximately 3-fold and LV GLUT-1 protein increased 1.5-fold after 14 days of hypobaric hypoxia vs. both pair-fed and normal controls. RV GLUT 4 mRNA decreased to 26% and RV GLUT-4 protein decreased to 54% of normal control levels as a result of 2 days of hypobaric hypoxia. RV GLUT-4 mRNA decreased to 64% of normal control levels with no change in RV GLUT-4 protein as a result of 2 days of fasting. We conclude that hypobaric hypoxia increases cardiac GLUT-1 expression at the pretranslational level in both ventricles. The greater increase in GLUT-1 protein on the right suggests an additive effect of pressure overload. GLUT-4 expression is reduced early in the development of RV hypertrophy. PMID- 1415539 TI - Single umbilical artery ligation-induced fetal growth retardation: effect on postnatal adaptation. AB - To assess whether prolonged intrauterine stress and resultant fetal growth retardation result in depletion of adrenal catecholamines and alter the adrenergic signal transduction system, we studied newborn sheep after single umbilical artery ligation (SUAL)-induced growth retardation. The animals were delivered at term, and postnatal cardiovascular, pulmonary, endocrine, and metabolic responses were measured. We also evaluated the status of myocardial and pulmonary beta-adrenergic receptor number and function. SUAL caused significant growth retardation but relative preservation of brain and adrenal gland weight and adrenal catecholamine content. Blood pressure, plasma free fatty acid, and glucose responses at birth were blunted in SUAL animals. The plasma epinephrine (Epi) and norepinephrine levels were comparable in both groups for the first 2 h of age. By 4 h, both plasma concentration and plasma appearance rate of Epi were reduced to 40% of control in SUAL animals (P less than 0.05). Neither beta receptor density, affinity, nor adenylate cyclase activity were altered by SUAL in either cardiac or pulmonary membranes. These results suggest that, rather than overt depletion, there is relative sparing of initial adrenal medullary function that later waned. This response and preservation of the beta-adrenergic signal transduction system may represent partial compensation for the physiological stress induced by SUAL. PMID- 1415540 TI - Stable isotope tracer analysis by GC-MS, including quantification of isotopomer effects. AB - In metabolic tracer studies it is frequently useful to infuse tracers that are differently labeled variants of the same molecule. These tracers are known as isotopomers. Analysis of the enrichment of each isotopic analogue can be accomplished by gas chromatography-mass spectrometry (GC-MS). However, the raw GC MS data must be corrected to give the information required. This paper addresses how to transform the raw GC-MS data, consisting of relative abundance ratios at specific ion masses, into relative molar ratios of tracer and tracee molecules. Several correction factors are necessary. First, the background must be measured and corrected for, since it is always present in the sample. Second, the abundances in the spectrum of the labeled molecule are different from those in the unlabeled molecule, and this proportionality "skew" is corrected. A third correction factor accounts for the overlapping spectra of two or more isotopomers that cannot be measured independently. The final correction removes the "double vision" effect that may appear in some spectra due to the presence of (M - H)+ species. PMID- 1415542 TI - Regional differences in gut blood flow and mucosal damage in response to ischemia and reperfusion. AB - Ischemia and reperfusion of the small intestine and colon in rats were produced by reversible occlusion (for 30 min and 1 or 3 h) of the superior mesenteric artery and the aorta above the inferior mesenteric artery. Despite a greater reduction of mucosal perfusion in the colon than in the small intestine with 30 min of ischemia, the depth of mucosal damage was significantly smaller in the former than in the latter. Thirty minutes of ischemia followed by 1 h of reperfusion induced an increase in polymorphonuclear leukocyte infiltration in both locations. Exacerbation of mucosal injury occurred only in the small intestine, suggesting that reperfusion injury is independent of polymorphonuclear leukocyte infiltration. Reperfusion after 1 or 3 h of ischemia did not exacerbate mucosal damage in either location. Allopurinol significantly diminished the exacerbation of injury after reperfusion in the small intestine. The protective effect of allopurinol, however, was neither associated with an improvement in perfusion nor a reduction in polymorphonuclear leukocyte infiltration. These data indicate that there is a window (30 min) of reperfusion injury in the small intestine, but there is no evidence of reperfusion injury in the colon. PMID- 1415541 TI - Hypoxic liver injury and the ameliorating effects of fructose: the "glucose paradox" revisited. AB - It has been independently postulated that nutritional status is a modulator of the hepatic injury response to hypoxia and that glucose may be a poor substrate for hepatocellular metabolism. This study provides data linking these two concepts within the framework of metabolic zonation of the liver. With the use of a hypoxically perfused isolated rat liver model, cellular injury, as reflected by aspartate aminotransferase (AST) release, was significantly greater in the liver of fasted (mean AST 489 U/g liver at 3 h) than fed (40 U/g) animals. The extent of injury during hypoxia was decreased to a comparable degree in fasted livers perfused with Wisconsin solution (27 U/g) or 20 mM fructose (51 U/g). Perfusion with (11.5 mM) glucose plus insulin provided no hepatoprotection (791 U/g); however, supraphysiological amounts of glucose (100 mM) with (310 U/g) or without (321 U/g) insulin (10 U) or dihydroxyacetone (220 U/g) provided a modest reduction in AST release. Cellular injury measured by trypan blue uptake showed a marked zonal pattern, with upstream regions incurring greater parenchymal and nonparenchymal injury than downstream areas. These data that indicate that exogenous glucose is poorly utilized as an energy substrate by the liver during hypoxia are consistent with data from the fasted-refed rat model, suggesting a "glucose paradox" in the liver. The findings also suggest that low levels of oxygen are an important factor mediating "hypoxic" liver injury. PMID- 1415543 TI - Subacinar distribution of hepatocyte membrane potential response to stimulation of gluconeogenesis. AB - Isolated rat livers were perfused and the membrane potentials of matched periportal and pericentral hepatocytes were determined using glass microelectrodes. O2 uptake and gluconeogenesis were increased by both phenylephrine and glucagon and the extent of the increase was not affected by the direction of perfusion. With no exogenous substrate, hepatocyte membrane potentials were approximately -27 mV. No gradients were found. Substrate produced hyperpolarization in all hepatocytes, with a small but significant gradient produced. Phenylephrine-induced hyperpolarization was higher in periportal than in pericentral hepatocytes during anterograde perfusion, but reversed during retrograde perfusion. Similar effects on membrane potential were produced by phorbol myristate acetate (PMA). Glucagon hyperpolarized homogeneously during both anterograde and retrograde perfusion with no gradients across the acinus. Octanol addition during glucagon stimulation, however, resulted in heterogeneity similar to phenylephrine or PMA. Thus when hepatocytes are stimulated by substrate or hormones, the degree of hepatocyte membrane potential heterogeneity across the acinus is highly dependent on the nature of the stimulus. We propose that the differential hormone effects on hepatocyte membrane potential may be mediated at least in part by differential modulation of cell to cell communication via gap junctions. PMID- 1415544 TI - CCK, bombesin, and carbachol stimulate c-fos, c-jun, and c-myc oncogene expression in rat pancreatic acini. AB - To identify possible nuclear signals mediating long-term regulation of the pancreas by gastrointestinal hormones, the expression of c-fos, c-jun, and c-myc was investigated in rat pancreatic acini. Stimulation of the acini with cholecystokinin octapeptide (CCK-8, 100 pM), bombesin (10 nM), or carbachol (10 microM), but not gastrin (100 nM), secretin (100 nM), or vasoactive intestinal peptide (10 nM) induced an increase in oncogene mRNA expression. The percent increases of c-fos, c-jun, and c-myc mRNA were 207 +/- 40, 171 +/- 26, and 46 +/- 19 (n = 5) for CCK-8; 223 +/- 71, 159 +/- 31, and 43 +/- 21 (n = 5) for bombesin; and 125 +/- 51, 123 +/- 58, and 67 +/- 19 (n = 5) for carbachol, respectively. CCK-induced increases in oncogene mRNA were rapid and transient. c-fos and c-jun mRNA levels were increased after 30 min stimulation, peaked at 1 h, and returned to basal level in 2 h. Activation of c-myc was more prolonged with levels remaining elevated for at least 3 h. The effects of CCK-8 were concentration dependent. Detectable stimulation was seen at 10 pM; maximal stimulation occurred at 10 nM and was not affected by further increase in the concentration of CCK-8. JMV-180, a high-affinity site CCK receptor agonist and low-affinity site antagonist, alone did not stimulate c-fos mRNA expression but inhibited c-fos mRNA expression induced by CCK-8. These results suggest that the interaction between CCK and the low-affinity state of the CCK receptor is responsible for oncogene activation. PMID- 1415545 TI - Lytic effects of mixed micelles of fatty acids and bile acids. AB - It has been hypothesized that bile acids and fatty acids promote colon cancer. A proposed mechanism is a lytic effect of these surfactants on colonic epithelium, resulting in a compensatory proliferation of colonic cells. To investigate the first step of this hypothesis, we studied the lytic activity of fatty acids and physiological mixtures of fatty acids and bile acids. Experiments were performed in both erythrocytes and cultured Caco-2 cells, a model system for intestinal epithelium. Fatty acids with a chain length of 10 C atoms or more were lytic, and the hemolytic activity increased in the order C10:0 less than C18:0 less than C16:0 less than C12:0 less than C14:0 much less than C18:1 approximately C18:2 but was not dependent on their critical micellar concentration. Addition of a sublytic, submicellar concentration of cholate resulted in the formation of highly lytic mixed micelles. Lytic activity of these mixed micelles was closely associated with their micellar aggregation as determined in parallel incubations using a fluorescent micellar probe. With use of identical concentrations of fatty acids and mixed micelles, lysis of erythrocytes was highly correlated (r greater than 0.95) with lysis of Caco-2 cells measured by either release of the apical membrane-marker alkaline phosphatase or the cytosolic marker lactate dehydrogenase. This indicates that the cytolytic activity of these surfactants is not cell-type dependent. Addition of bile acids in concentrations corresponding with the total bile acid concentration in human fecal water resulted in an increased lytic activity of fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415547 TI - cDNA cloning and localization of a band 3-related protein from ileum. AB - A Cl(-)-HCO3- exchanger in the brush-border membrane mediates active Cl- absorption and regulates intracellular pH in rabbit ileum. The molecular identity of the ileal Cl(-)-HCO3- exchanger has not been established. The best characterized plasma membrane Cl(-)-HCO3- exchanger is erythroid band 3. Structurally related proteins in nonerythroid tissues comprise an anion exchanger (AE) family. We used the polymerase chain reaction to amplify and clone a cDNA encoding an ileal band 3-related protein (B3RP) from rabbit ileal enterocytes. The composite sequence is 3,909 bp and is predicted to encode a protein of 136 kDa. The deduced amino acid sequence is 95% identical to murine renal AE2, indicating that ileal B3RP is rabbit AE2. Antisera generated against a cytoplasmic fragment of ileal B3RP recognized a 160- to 170-kDa polypeptide in the brush-border membrane, but not the basolateral membrane, of ileal crypt and villus enterocytes. This correlates with previous studies indicating that a Cl(-) HCO3- exchange is present in brush-border but not basolateral membrane vesicles from rabbit ileal enterocytes. We conclude that ileal B3RP is a product of the AE gene family, and is present in the brush-border of ileal enterocytes, where it may mediate Cl(-)-HCO3- exchange. PMID- 1415546 TI - Carrier-mediated transport of tetrabromosulfonephthalein by rat liver plasma membrane vesicles. AB - To investigate the molecular requirements and mechanisms for the hepatic uptake of phthaleins, the transport of tetrabromosulfonephthalein (TBS) was investigated in basolateral rat liver plasma membrane vesicles. TBS uptake was electrogenic as greatly accelerated by the creation of a positive-inside membrane potential by the addition of valinomycin in the presence of an inwardly directed potassium gradient. No effect was observed when the ionophore was added in the presence of a sodium gradient. The transport occurred into an osmotic-sensitive space and was saturable with an apparent Michaelis constant of 5.32 +/- 0.56 microM and a maximal velocity of 9.23 +/- 0.25 nmol.s-1.mg protein-1 (mean +/- SD, n = 3 experiments). TBS uptake was directly related to the extra-vesicular pH, indicating the deprotonated quinoid negative-charged form of the dye as the transported species. In contrast, TBS uptake was inversely related to the intravesicular pH, suggesting that protonation inside the vesicles may act as an efficient trap in transport process. Addition of polyclonal monospecific anti bilitranslocase antibody to liver vesicles specifically inhibited TBS uptake rate (3.27 +/- 0.17 vs. 5.82 +/- 0.61 nmol.s-1.mg protein-1, n = 3, P less than 0.001). These data indicate that TBS is electrogenically transported across the liver cell plasma membrane by bilitranslocase. They also indicate that the presence of a negative charged group on the benzenic ring of the ligand is important in accounting for the transport. PMID- 1415548 TI - Effects of nerve stimulation and zymosan on glycogenolysis in perfused livers from cold-exposed rats. AB - The effects of sympathetic nerve stimulation and zymosan (cell wall particles from yeast) on glycogenolysis were studied in perfused livers from rats kept for 5 and 20 days at 4 degrees C. The rate of glycogenolysis induced by nerve stimulation decreased significantly without any decrease in norepinephrine outflow during cold exposure, and the rate induced by norepinephrine did not change. By contrast, the rate of zymosan-induced glycogenolysis increased markedly during cold exposure. The rats with denervated hepatic nerves did not show the increased response to zymosan. In cold-exposed rats, both mepacrine and ibuprofen inhibited the effects of zymosan and of nerve stimulation without any inhibition of the outflow of norepinephrine. Neither inhibitor had any effect on the effects of norepinephrine. The metabolic effects of nerve stimulation and zymosan were not additive in cold-exposed rats. These results suggest that cold exposure may modulate the metabolism of arachidonic acid in Kupffer cells via hepatic nerve and decrease the eicosanoid-dependent glycogenolysis by nerve stimulation. PMID- 1415549 TI - Development of Ca2+ homeostasis in epithelial cells from embryonic and neonatal intestine. AB - The fluorescent probe fura-2 was used to assay Ca2+ levels in epithelial cell suspensions from embryonic and neonatal chick duodenum. Cell preparations maintained high viability, completely hydrolyzed fura-2/AM to fura-2, retained 92% of cellular fura-2 within the cytoplasmic compartment, and gave low autofluorescence values during assay. Fura-2 leakage from loaded cells occurred at all ages, but could be corrected for in subsequent calculations of cellular Ca2+. Cytoplasmic Ca2+ concentration was 76-80 nM in cells from 14- to 16-day embryonic intestine, rose significantly to 92-98 nM at 17-20 days, and reached 209 nM at 1-day post-hatch when assayed in buffers containing 1.3 mM Ca2+. The developmental rise in cytoplasmic Ca2+ was accompanied by an enhanced ability of cells to maintain a constant Ca2+ concentration at increased levels of extracellular Ca2+ and by a highly correlated rise in alkaline phosphatase (ALP) activity. Epithelial Ca2+ subsequently decreased to the "adult" value of 133-142 nM and was constant along the crypt-villus axis of neonatal intestine. These results verify that fura-2 can be used to compare baseline cytoplasmic Ca2+ values of epithelial cells from developing intestine, reveal that significant changes in Ca2+ homeostasis occur during ontogeny, and suggest that epithelial Ca2+ may modulate ALP activity during the differentiation of embryonic enterocytes. PMID- 1415550 TI - Sex differences in hepatic fatty acid uptake reflect a greater affinity of the transport system in females. AB - In this study, we examined the hypothesis that the reported sex difference in hepatic free fatty acid (FFA) uptake involves the putative FFA transport system, the plasma membrane fatty acid binding protein (FABPpm). In hepatocytes isolated from both male and female rats, initial [3H]oleate uptake velocity reflected transmembrane influx and not subsequent metabolism and was a saturable function of the unbound oleate concentration. Although Vmax values were similar (61 +/- 2 vs. 65 +/- 5 pmol.min-1.5 x 10(4) cells-1 for females and males, respectively), the apparent Km was significantly smaller in females (40 +/- 4 vs. 90 +/- 11 nM; P less than 0.05), reflecting faster influx velocities in female cells over a range of unbound oleate concentrations. The oleate efflux rate constant was also greater in females (0.280 +/- 0.014 vs. 0.198 +/- 0.020 min-1; P less than 0.05) despite their greater hepatic content of cytosolic FABP. Finally, despite the greater rates of transmembrane FFA flux in female hepatocytes, the surface expression of FABPpm was virtually identical in the two sexes (2.5 +/- 0.5 vs. 2.4 +/- 0.4 microgram/10(6) cells). Collectively, these data indicate that at FFA to-albumin ratios occurring in vivo the plasma membrane of female hepatocytes transports oleate bidirectionally at a greater rate than that of male hepatocytes. A sex-related difference in the functional affinity of FABPpm for FFA appears the most likely explanation for the greater oleate uptake in females. PMID- 1415551 TI - Bile salt hydrophobicity controls vesicle secretion rates and transformations in native bile. AB - After drainage of the bile salt pool, we infused unanesthetized bile fistula prairie dogs (Cynomys ludovicianus) intravenously with taurine-conjugated chenodeoxycholate (TCDC), cholate (TC), ursodeoxycholate (TUDC), and ursocholate (TUC) in concentrations that attained greater than 94% enrichment of biliary bile salts. With decreases in bile salt hydrophobicity, maximum steady state lecithin and to a lesser extent cholesterol secretion rates decreased in the rank order, TCDC greater than TC greater than TUDC greater than TUC. By phase analysis, TCDC rich and TC-rich biles plotted inside their respective micellar zones, whereas TUDC-rich and TUC-rich biles plotted outside and were so-called "supersaturated" with cholesterol. Quasi-elastic light scattering and electron microscopy, when performed within 30 min of collection, revealed unilamellar vesicles in all biles. By 24 h, vesicles in TCDC-rich and TC-rich biles had dissolved into mixed micelles, whereas vesicles in TUDC-rich biles formed mixed micelles plus multilamellar liquid crystals, and vesicles in TUC-rich biles formed multilamellar liquid crystals exclusively. Because cholesterol/phospholipid molar ratios of multilamellar liquid crystals were less than or equal to 1, cholesterol monohydrate crystals did not form in these biles. We conclude that, despite drastic alterations in bile salt detergency, unilamellar vesicles are the final common pathway for lecithin and cholesterol secretion into bile. During equilibration of bile, the fate of unilamellar vesicles may be micellar, micellar plus liquid crystalline, or liquid crystalline only depending on the detergency (i.e., hydrophobic-hydrophilic balance) of the secreted bile salt. PMID- 1415552 TI - Effects of agonists on p21ras and ras-related proteins in rat pancreatic acinar cells. AB - This study shows the presence of seven different low-molecular-weight GTP binding proteins (smg proteins) with molecular masses between 18 and 27 kDa in subfractions of rat pancreatic acinar cells. After stimulation of isolated intact and permeabilized pancreatic acinar cells with cholecystokinin octapeptide (CCK OP), the diacylglycerol (DG) analogue 12-O-tetradecanoylphorbol 13-acetate (TPA), vasoactive intestinal peptide (VIP), adenosine 3',5'-cyclic monophosphate (cAMP), or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), [alpha-32P]GTP binding to 21- to 22-kDa smg protein(s) in microsomal membranes (MM) was reduced, whereas the [alpha-32P]GTP binding to 23-kDa protein(s) was enhanced. In addition, prestimulation of permeabilized cells with GTP gamma S caused enhancement of [alpha-32P]GTP binding to a 19-kDa protein in MM [immunologically identified as the ADP-ribosylation factor (arf)]. In the presence of cytosol, direct addition of GTP gamma S to isolated MM resulted in an apparent translocation of the 19-kDa protein (arf) from the cytosol to membranes. This indicates increased association of arf with the membrane in its GTP-bound state. In CCK-OP-prestimulated acinar cells, [alpha-32P]GTP binding to plasma membrane-located 21- to 22-kDa proteins (immunologically identified as p21ras proteins) was enhanced, suggesting that there is an interrelationship between p21ras proteins and CCK receptors. Our results give evidence for a role of 19-kDa, 21- to 22-kDa, and 23-kDa smg proteins in cAMP-protein kinase A- and DG-protein kinase C-mediated stimulation of intracellular pathways in pancreatic acinar cells. PMID- 1415553 TI - Interleukin-1 beta acts at hypothalamic sites to inhibit gastric acid secretion in rats. AB - It has been established that interleukin-1 beta (IL-1 beta) injected into the cerebrospinal fluid inhibits gastric acid secretion in rats. Brain sites of action of IL-1 beta were investigated in conscious rats implanted unilaterally with chronic hypothalamic cannula. Gastric acid secretion was monitored 2 h after pylorus ligation. Human recombinant IL-1 beta (10 ng) microinjected into the medial preoptic area, anterior hypothalamus, and paraventricular nucleus inhibited gastric acid secretion by 76-83%. IL-1 beta microinjected into the ventromedial hypothalamus and other hypothalamic sites outside of responsive sites had no effect. IL-1 beta inhibitory action in the medial preoptic area was dose related (0.1-10 ng), prevented by indomethacin (5 mg/kg ip), and mimicked by prostaglandin E2. These results show that IL-1 beta acts in the medial preoptic area/anterior hypothalamus and paraventricular nucleus to inhibit acid secretion in pylorus-ligated rats and that IL-1 beta action is likely to involve prostaglandin E2. PMID- 1415554 TI - Migration of IEC-6 cells: a model for mucosal healing. AB - Cell migration is the principal force behind the early restitution of erosions of the mucosa of the gastrointestinal tract. Despite the importance of cell migration to healing, no attempts to study the process in culture have been reported. We have attempted to standardize conditions for migration and test the migration responses of the small intestinal epithelial crypt cell line IEC-6 in some experimental situations already well known in vivo. We found good correspondence between in culture and in vivo on the following points: 1) migration was independent of DNA synthesis; 2) DNA synthesis was not concentrated at the wound edge; and 3) inhibition of actin polymerization stopped migration altogether. In addition, the presence of an extracellular matrix maximized migration. Protein inhibitors with different modes of action inhibited cell migration to different degrees, not always commensurate with their inhibition of protein synthesis. Cell surface proteoglycans were important; hyaluronic acid had an effect, but the secretion of a migration-stimulating substance by wounded cells was equivocal. Significantly, alpha-difluoromethylornithine (DFMO), which inhibits ornithine decarboxylase and polyamine synthesis, almost totally prevented cell migration. Because DFMO also prevents healing of mucosal erosions in vivo, we believe that this model can be used, keeping in mind its spatial limitations, to study the process of cell migration involved in the early restitution of mucosal erosions. PMID- 1415555 TI - CFU-rAM, the origin of lung macrophages, and the macrophage lineage. AB - Macrophage precursors and their progeny have been identified in early rat embryos with the use of a peroxidase-coupled marker, isolectin B4 of Griffonia simplicifolia (GSA I-B4). The macrophage lineage can be traced back to actively dividing GSA-positive angular cells present in the mesenchyme of late neurulas. These increase in number and establish residence successively in rudiments of the central nervous system, liver, and lungs. In organ-cultured fetal lungs they transform directly into a self-replicating population of macrophages responsive to colony-stimulating factors. The angular cell therefore can be seen as the source of lung macrophages during prenatal life. The extent to which this manner of production continues in postnatal life is unclear, but it appears that central hematopoietic tissues (bone marrow, spleen) may generate macrophages by a direct pathway from early-committed progenitors as well as indirectly through a series of intermediate stem cells. Considering the wealth of new information available from diverse studies in specialized culture environments and to a lesser extent from studies in vivo, it is time to integrate these findings into a more comprehensive theory of macrophage origin and fate than we have at present. PMID- 1415556 TI - A novel system for the culture of human lung: lung development and the response to injury. AB - Existing methods of fetal lung organ culture are complicated and require special skills. With the use of a polyester-based plastic sheet, we have developed a simpler human fetal lung organ culture that is viable for 6 wk. This novel method permits the study of growth and differentiation, pulmonary surfactant secretion, and the response of human lung tissue to injury in vitro. Lung tissues, obtained from human fetuses ranging in gestational age from 14 to 18 wk, were cultured on the polyester sheet in Dulbecco's modified Eagle medium supplemented with 15% fetal calf serum and gentamicin. Microscopic study of the fetal lung before culturing revealed round epithelial tubules, lined by glycogen-rich columnar cells and a thick cellular interstitium. After 1 wk in culture, morphological examination showed the development and expansion of alveolar saccules and thinning of the interstitium; type I and II pneumocytes as well as fibroblasts and myofibroblasts were present. Lipid analysis of the tissues, 2 wk after the initiation of the culture, demonstrated a high percentage of dipalmitoyl phosphatidylcholine characteristic of pulmonary surfactant. Treatment of the organ culture with asbestos fibers induced type II cell hyperplasia, increased numbers of collagen fiber bundles within the interstitium, and the accumulation of multi-lamellated surfactant material within the alveolar lumens. We conclude that this organ culture system is suitable for studying lung growth, development, and injury in human tissue. PMID- 1415558 TI - Binding and uptake of surfactant protein B by alveolar type II cells. AB - Surfactant protein B (SP-B, mol wt 9,000, reduced) is a low-molecular-weight hydrophobic protein found in organic extracts of lung surfactant. The interaction of iodinated bovine SP-B (125I-SP-B) and isolated rat alveolar type II cells was examined. The association of SP-B with the lung cells was time and temperature dependent; type II cells exhibited time-dependent binding (at 4 degrees C) and uptake (at 37 degrees C) of SP-B. Binding of phospholipid-poor 125I-SP-B was linearly related to the external SP-B concentration from 0.25 to 60 microgram/ml and was not inhibited by a 60-fold excess of unlabeled SP-B. However, the binding of 125I-SP-B reconstituted with bovine surfactant or with phospholipid-containing liposomes occurred through a high-affinity, saturable process and could be inhibited with unlabeled SP-B. By Scatchard analysis, half-maximum binding in the presence of surfactant occurred at 3.1 +/- 0.7 micrograms SP-B/ml. Saturable binding of SP-B reconstituted with surfactant also occurred with other cell types. The results indicate that SP-B was bound and internalized by type II cells. The apparent lack of specificity in the absence of phospholipid may have been due to the self-association of SP-B. The reconstitution of SP-B with phospholipid altered the binding of phospholipid-poor SP-B from a nonspecific process to a high-affinity process consistent with a cell surface binding site. PMID- 1415557 TI - Role of endothelin-1 in regulating proliferation of cultured rabbit airway smooth muscle cells. AB - Increased expression of the potent vasoconstrictor and bronchoactive peptide, endothelin-1 (ET-1), has recently been demonstrated in airway epithelial and endothelial cells of asthmatic patients. To identify its potential role in contributing to airway smooth muscle (ASM) hyperplasia, a characteristic feature of asthmatic airways, the mitogenic action of ET-1 was investigated in cultured rabbit ASM cells. ET-1 elicited significant dose-dependent (10(-12)-10(-6) M) increases in ASM cell number, with a mean potency (i.e., -log mean effective dose) of action of 9.82-log M. ET-1 also acutely stimulated intracellular inositol 1,4,5-trisphosphate accumulation. The latter response was blocked by phospholipase C inhibition with neomycin; however, neomycin had no effect on the promitogenic action of ET-1. By contrast, the ASM cell proliferative response to ET-1 was independently inhibited by pertussis toxin, inhibitors of phospholipase A2, cyclooxygenase, and thromboxane A2 (TxA2) synthesis, as well as blockade of the TxA2 receptor. Moreover, in complementary studies, we found that administration of the stable TxA2 mimetics, carbocyclic TxA2 (CTA2) and U-46619, induced ASM cell proliferation and that ET-1 evoked the release of endogenous TxA2 from the ASM cells. Collectively, these observations provide new evidence that 1) ET-1 is a potent mitogen of ASM cells, 2) the promitogenic effect of ET-1 is associated with activation of a pertussis toxin-sensitive G protein coupled to stimulation of phospholipase A2, and 3) the latter mediates ASM cell proliferation via the release and autocrine mitogenic action of TxA2. The findings support a potential role for ET-1 in mediating the characteristic hyperplasia of ASM in asthma. PMID- 1415559 TI - Kinetics of pulmonary superoxide dismutase in interleukin-1-induced oxygen tolerant rats. AB - We have previously demonstrated that tracheal insufflation of interleukin-1 alpha (IL-1) enhances pulmonary Mn superoxide dismutase (Mn SOD) activity and protects rats against O2 toxicity (M. F. Tsan, C. Y. Lee, and J. E. White. J. Appl. Physiol. 71: 688-697, 1991). In this study, we investigated the kinetics of mRNA, specific (immunoreactive) proteins, and enzyme activities of pulmonary Mn SOD and Cu,Zn SOD in IL-1-induced O2-tolerant rats. At 1 day after IL-1 (5 micrograms) insufflation and O2 exposure, levels of Mn SOD mRNA and specific protein, but not enzyme activity, were markedly elevated. At 2.3 and 7 days after O2 exposure, levels of Mn SOD mRNA, specific protein, and enzyme activity were all increased in IL-1-treated animals. In contrast, in control rats at 2.3 days after O2 exposure, level of Mn SOD mRNA was markedly elevated, whereas levels of specific protein and enzyme activity were decreased. Levels of pulmonary Cu,Zn SOD mRNA, specific protein, and enzyme activity were unchanged in control and IL-1-treated rats, except that in IL-1-induced long-term O2-tolerant rats (7 days after O2 exposure), they were all increased. Since at 7 days after IL-1 insufflation, normoxia-exposed rats did not show increased levels of pulmonary Mn SOD or Cu,Zn SOD mRNA, the increased levels of pulmonary SOD seen in IL-1-induced long-term O2 tolerant rats are, at least in part, due to the effect of O2 exposure. PMID- 1415560 TI - Alveolar type II cells synthesize hydrophobic cell-associated proteoglycans with multiple core proteins. AB - Type II alveolar epithelial cells interact with the extracellular matrix via cell surface receptors for matrix ligands. Cell surface proteoglycans, which are hydrophobic due to their membrane insertion domains, are one of several classes of molecules that may be receptors for matrix ligands. To analyze the hydrophobic proteoglycans synthesized by adult alveolar type II cells, we labeled these cells with 35SO4 and [3H]leucine in short-term primary cultures. Cell-associated hydrophobic proteoglycans and culture medium-derived proteoglycans were purified and characterized. Both the hydrophobic proteoglycans and medium-derived proteoglycans, which were not hydrophobic, had mainly heparan sulfate glycosaminoglycans. Analysis of core proteins of the hydrophobic proteoglycans showed three proteins, 47, 65, and 90 kDa. The 47- and 65-kDa core proteins were substituted only with heparan sulfate chains. The 90-kDa core protein was seen only after digestion with both heparitinase and chondroitin ABC lyase, suggesting it was a hybrid having both heparan sulfate and chondroitin-dermatan sulfate chains. These findings were confirmed by iodination of the core proteins. The hydrophobic cell-associated proteoglycans inserted into artificial liposomes, whereas the medium-derived molecules did not. These data document heterogeneity in core protein and glycosaminoglycan chains among hydrophobic proteoglycans synthesized in vitro by adult alveolar type II cells. These molecules may have diverse functions in regulating type II cell interaction with the extracellular matrix. PMID- 1415561 TI - Effect of food restriction on hyperoxia-induced lung injury in preterm guinea pig. AB - Undernutrition may exacerbate hyperoxia-induced lung injury, a finding that may be of significance in the early clinical management of the premature human infant. Addressing this specific problem, we found that 72 h of food restriction in guinea pig pups delivered 3 days preterm increased mortality rates among pups exposed to 95% oxygen (8/18) and yet had no effect on 21% oxygen (air)-exposed pups (0/10). Reduced tolerance of hyperoxic conditions was not, however, associated with increased lung injury, assessed as pulmonary microvascular leakage. Pulmonary antioxidant enzyme activities [Cu,Zn superoxide dismutase (SOD), Mn SOD, glutathione peroxidase, and catalase] were unaltered by starvation or hyperoxia. Lung glutathione concentration was slightly decreased after food restriction, whereas hyperoxic exposure did not change either lung or bronchoalveolar lavage fluid glutathione concentrations or lung antioxidant enzyme activities. Increased susceptibility to the lethal effects of oxygen in the starved preterm guinea pig pup could not be attributed to a deficiency of pulmonary antioxidant defenses. PMID- 1415562 TI - Stimulation of fetal rat lung cell proliferation in vitro by mechanical stretch. AB - On the basis of in vivo animal studies and on experiments of nature, it has been suggested that fetal breathing movements are essential for normal lung growth in utero. To study this hypothesis in vitro, we examined the effect of mechanical stretch on proliferation of fetal rat lung cells maintained in organotypic culture to provide a three-dimensional matrix. Initial studies demonstrated that stretch-mediated effects on cell division and DNA synthesis in such cultures were influenced by cell inoculation density, fetal calf serum concentration, and by the amplitude, frequency, periodicity, and duration of the applied stretch. After a 48-h exposure to an intermittent stretch pattern (5% elongation, 60 stretches/min for 15 min of each hour), cell number increased 10% (P less than 0.05), cell doubling time was reduced from 71 to 55 h (P less than 0.05), [3H]thymidine incorporation into DNA increased 61% (P less than 0.01), and the [3H]thymidine-labeling index increased 2.8-fold (P less than 0.001) compared with nonstretched controls. This effect did not appear to be mediated by prostaglandins or leukotrienes because the prostaglandin synthase inhibitors ibuprofen (2.5-50 microM) or BW 755C (5 microM), leukotriene biosynthesis inhibitors BW 755C (5 microM) or MK-886 (0.3 microM), and leukotriene D4 receptor antagonist MK-571 (0.3 microM) did not block stretch-mediated effects. We conclude that mechanical forces act directly to stimulate fetal rat lung cell growth and that these results are compatible with a significant role for fetal breathing in normal fetal lung growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415563 TI - Effects of hypoxia and other vasoactive agents on pulmonary and cerebral artery smooth muscle cells. AB - Smooth muscle cells (SMC) were isolated from cat cerebral arteries and three sizes of pulmonary artery (less than 200-, 200- to 600-, and greater than 800 microns diameter) and used within 72-96 h. Change in cell length in response to hypoxia and other vasoactive agents was measured in a specially constructed cell chamber on an inverted microscope. Pulmonary artery SMC responded to hypoxia differently according to artery size. SMC from less than 200- and 200- to 600 microns-diameter pulmonary arteries shortened 18.6 +/- 4.85 and 24.2 +/- 2.70%, respectively. However, SMC from greater than 800-microns-diameter pulmonary arteries shortened 0.81 +/- 0.44%. Cerebral artery SMC plated on a flexible polydimethyl siloxane membrane showed loss of tension during exposure to hypoxia. The shortening of SMC from the 200- to 600-microns pulmonary arteries was accompanied by myosin phosphorylation. SMC from greater than 800-microns-diameter pulmonary arteries and cerebral arteries contained myosin that did not phosphorylate during hypoxia. The SMC from both artery types responded to norepinephrine, serotonin, prostaglandin F2 alpha and indomethacin and exhibited alpha-adrenergic receptor population patterns similar to those of intact arteries. The pattern of hypoxic responses exhibited by these nondedifferentiated pulmonary and cerebral artery SMC supports the idea that, at least in the cat, the hypoxic sensor is located within the SMC. PMID- 1415564 TI - Cell volume regulation in rat thin ascending limb of Henle's loop. AB - Thin ascending limb cells of Henle's loop from Wistar rats were studied with in vitro microperfusion and video-optical techniques to investigate their ability in regulating cell volume during osmotic shock and to identify mechanisms of ion transport involved in the process. These cells showed a clear volume regulatory decrease (VRD) response in hyposmotic medium, but no volume regulatory increase in hyperosmotic medium. The presence of barium in the bath abolished VRD. Removal of K+ from bath and perfusate also inhibited the VRD response. Reintroduction of K+ in hyposmotic conditions reestablished cell volume regulation. Introduction of anthracene-9-COOH to the basolateral medium blocked cell volume regulatory response. Cl- removal from perfusate and bath solutions also inhibited VRD, probably because of a significant intracellular Cl- depletion. Exposure of cells to ethylene glycol-bis(beta-aminoethyl ether)-N,N,N'N'-tetraacetic acid in perfusate and bath solutions reduced significantly Ca2+ concentration and impaired VRD. Reintroduction of Ca2+ in hyposmotic conditions restored volume regulation. The presence of ouabain in basolateral medium also inhibited VRD. These data suggest that the following mechanisms in the basolateral membrane are involved in VRD response: K+ and Cl- conductive pathways, which might be Ca2+ dependent for activation, and an Na(+)-K(+)-adenosinetriphosphatase. PMID- 1415565 TI - Colocalization and release of angiotensin and renin in renal cortical cells. AB - Angiotensin is generated within the kidney, but the precise loci for the formation of angiotensin I (ANG I) and angiotensin II (ANG II) have not been demonstrated. We performed electron microscopy immunocytochemistry in kidney sections of 10-day-old (newborn) and adult Wistar-Kyoto (WKY) rats using specific antibodies to renin, ANG I, ANG II, and angiotensinogen (AO). Renin, ANG I, ANG II, and AO were present in juxtaglomerular (JG) cells. Renin was largely confined to cytoplasmic granules; ANG I and ANG II were colocalized to these granules but also were present in the cytoplasm; AO was distributed throughout the cytoplasm. AO also was present in a renal cortical distribution in proximal tubular cells. Northern blot analysis demonstrated AO mRNA in total kidney and liver but not in renal microvessels. Using the reverse hemolytic plaque assay, we demonstrated release of ANG I and renin from individual renocortical cells of adult WKY rats. Under control conditions, the number of releasing cells was 11 +/- 1 for ANG I and 10 +/- 1 for renin. Addition of rat renin inhibitor (RI) (1 x 10(-5) M), which inhibited renin activity in the medium from 37 to 9 pg ANG I.ml-1.h-1, did not alter ANG I plaque number. Addition of rat AO increased ANG I plaque number to 17 +/- 2 (P less than 0.05). Incubation with both RI and AO prevented the increase in ANG I plaque number obtained with AO alone. Enalapril treatment (7 days; n = 5) increased the number of plaque-forming cells to 22 +/- 2 for ANG I (P less than 0.0005) and to 39 +/- 7 for renin (P less than 0.001). The results suggest an intracellular location for AO and angiotensin and release of renin and ANG I by renal cortical cells and suggest that released angiotensin is produced intracellularly and that secretion of ANG I is augmented by converting enzyme inhibition. PMID- 1415566 TI - Extracellular ATP stimulates proliferation of cultured mesangial cells via P2 purinergic receptors. AB - We examined the role of the platelet product ATP in regulating replication and secretory activity of cultured rat mesangial cells (MCs). Extracellular ATP (25 100 microM) significantly increased [3H]thymidine uptake of growth-arrested MCs 2.1-fold; cell counts increased by 35.1%. Addition of ATP to MCs in combination with other platelet products, such as platelet-derived growth factor, isoform BB (100 ng/ml), and serotonin (1 microM), resulted in strong synergistic mitogenicity (up to 45.6-fold over control). As immediate signaling events following stimulation with ATP, we found increased production of inositol phosphates (3.2-fold increase for inositol bisphosphate and 1.6-fold increase for inositol trisphosphate by 30 s) and release of prostaglandin E2 (PGE2, 9.2-fold increase by 5 min). When we studied the rank order of potency of various ATP analogues for the production of inositol phosphates and PGE2, ATP, UTP, and adenosine 5'-O-(3-thio)triphosphate (ATP gamma S) were the most potent agonists. Although ATP and ATP gamma S were also strong mitogens, UTP was not. Additional inhibitor studies indicated that protein kinase C or cyclooxygenase products were not involved in the mitogenic effects of ATP. In summary, the major platelet product ATP is a potent comitogen for cultured MCs and strongly synergizes with other growth factors. The experiments with ATP analogues point to different receptors mediating mitogenesis, generation of inositol phosphates, and PGE2 production. The precise mechanism of the mitogenic action of ATP on MCs remains to be characterized. PMID- 1415567 TI - PAH/alpha-KG countertransport stimulates PAH uptake and net secretion in isolated rabbit renal tubules. AB - Possible stimulation of both basolateral uptake and net transepithelial secretion of p-aminohippurate (PAH) by PAH/alpha-ketoglutarate (alpha-KG) countertransport was examined in intact perfused and nonperfused rabbit proximal S2 renal tubules. Preloading tubules with alpha-KG (100 microM) for 30 min increased [14C]-PAH rate of uptake by nonperfused tubules and rate of net secretion by perfused tubules approximately three- to sixfold. During stimulation of net secretion, intracellular [14C]PAH concentration increased to about the same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na(+) dicarboxylate cotransport) in bathing medium during alpha-KG preloading eliminated stimulation of PAH transport. Addition of unlabeled alpha-KG (1 mM) to bathing medium stimulated efflux of [14C]PAH across the basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH/alpha-KG countertransport. Preloading with succinate (100 microM) also stimulated rates of [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only approximately 1.5-fold. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate [14C]PAH uptake by nonperfused tubules or net secretion by perfused tubules. Thus it seems most likely that succinate preloading stimulates PAH transport via metabolism, possibly by conversion to alpha-KG, not by direct countertransport for PAH. This study indicates for the first time in intact mammalian proximal S2 renal tubules that PAH/alpha-KG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration. PMID- 1415568 TI - Basolateral Na(+)-independent Cl(-)-HCO3- exchange in primary cultures of rat IMCD cells. AB - The role of anion exchange in the regulation of intracellular pH (pHi) under base load and steady-state conditions was investigated in confluent monolayers of rat inner medullary collecting duct (IMCD) cells in primary culture using the pH sensitive fluoroprobe 2,7-bis(carboxyethyl)-5(6')-carboxyfluorescein (BCECF). Recovery of pHi after imposition of a base load induced either by replacement of HCO3-/CO2 by N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) at the same extracellular pH (pHo) or deletion of Cl- from a HCO3-/CO2-buffered solution had an absolute requirement for Cl-, was Na+ independent, and was inhibited approximately 90% by 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). When pHo was decreased by lowering HCO3- concentration in the constant presence of 5% CO2, the rate of decrement in pHi was significantly blunted in the absence of Cl-. Imposition of a positive or negative diffusion potential of equal but opposite magnitude did not modify the anion exchange rate, confirming the electroneutrality of the process. Under steady-state conditions, pHi of cells bathed in a HCO3-/CO2-buffered solution was 7.33 +/- 0.06, significantly lower than that of cells bathed in a nominally HCO3-/CO2-free buffer (7.50 +/- 0.04), indicating that under physiological conditions the pathway functions as a base extruder. In studies performed on cells grown on permeable supports, the anion exchange pathway was found to be confined exclusively to the basolateral equivalent cell surface. In summary, confluent monolayers of rat IMCD cells in primary culture possess a Na(+)-independent, DIDS-inhibitable electroneutral Cl( )-HCO3- exchange pathway that is confined to the basolateral cell surface. The transporter is an important determinant of steady-state pHi and is the predominant mechanism whereby the cell recovers from imposed elevations in pHi. PMID- 1415569 TI - Angiotensin II receptor subtypes in cultured rat renal mesangial cells. AB - The selective angiotensin (ANG II) antagonists losartan (DuP 753) and PD 123319 have been shown to bind selectively to AT1 and AT2 subtypes, respectively. To characterize ANG II receptor subtypes in mesangial cells, washed membranes were incubated with 0.1 to 0.5 nM 125I-ANG II and increasing concentrations of competitors. The inhibition of 125I-ANG II binding by losartan and PD 123319 was biphasic, and LIGAND curve-fitting analysis revealed two populations of specific binding sites. One subpopulation comprised 86% of the total and showed high affinity for ANG II and losartan, but low affinity for the AT2 antagonists PD 123319 and CGP42112A, and thus appear identical to the recently cloned AT1 subtype. The remaining 14% of the sites showed nearly 100-fold lower affinity for losartan and 10,000-fold higher affinity for PD 123319 relative to AT1 sites. However, another AT2-selective antagonist, CGP42112A, showed little affinity for these sites. Both classes of binding sites were inhibited by guanosine 5'-O-(3 thiophosphate) and pertussis toxin treatment. We propose that there are two distinct G protein-coupled ANG II receptor subtypes (AT1A and AT1B) present in renal mesangial cells. PMID- 1415570 TI - In vitro perfusion of chinchilla thin limb segments: segmentation and osmotic water permeability. AB - The thin limb segments of the long loop of Henle are thought to play important roles in the urinary concentrating mechanism. In this study, we present new approaches to the identification, dissection, and in vitro perfusion of individual thin limb segments from all levels of the chinchilla renal medulla, including the deepest portions of the papilla. We have applied these techniques to the investigation of the osmotic water permeability along the chinchilla long loop of Henle. The results demonstrate that the osmotic water permeability of the thin descending limb is not uniformly high along its length, as previously thought, but that the distal 20% of the long-loop descending limb has a very low water permeability (approximately 50 microns/s). The transition to the low water permeability region of the thin descending limb is accompanied by a relatively abrupt change in morphology (increased cellularity and decreased diameter) that is readily perceptible in the perfused segments and even in the dissection dish. In contrast, the upper part of the chinchilla long-loop thin descending limb had an extremely high osmotic water permeability (greater than 2,000 microns/s) as observed in other species. Thin ascending limbs from deep in the inner medulla had water permeabilities that were indistinguishable from zero, as previously found in thin ascending limbs from near the inner-outer medullary junction. The presence of a low-water-permeability portion of the long-loop thin descending limb in chinchilla may have important implications with regard to the inner medullary concentrating process. A relatively low osmotic water permeability (397 microns/s) was also found in the deep inner medullary portion of the thin descending limb from the rat. PMID- 1415571 TI - Dietary protein modulates intrarenal distribution of renin and its mRNA during development. AB - To determine whether high protein feeding throughout development affects renal growth, renal hemodynamics, and the intrarenal distribution of renin and its mRNA in the adult animal, male Wistar rats were fed diets containing either 20% protein [normal (NP), n = 12] or 40% protein [high (HP), n = 12] from weaning until studied at 6 or 12 wk of age. Kidney weight, kidney weight-to-body weight ratio, cortical DNA content, and cortical protein-to-DNA ratio were higher in HP- than in NP-fed rats at 6 and 12 wk of age. Somatic and kidney growth response to HP was blunted by angiotensin II type 1 receptor antagonist Dup 753. Glomerular filtration rate and renal plasma flow were higher in HP- than in NP-fed rats at 6 and 12 wk of age. The intrarenal distribution of renin and renin mRNA, assessed by immunocytochemistry and in situ hybridization, respectively, were markedly different between the two groups. In NP-fed rats, renin and renin mRNA were confined to a juxtaglomerular location. In HP-fed rats, renin and its mRNA extended proximally along the afferent arterioles. The percentage of visible afferent arteriolar length containing renin or renin mRNA was higher in HP-fed rats (60 +/- 3.2 and 61 +/- 3.9%, respectively) than in NP-fed rats (39 +/- 2.5 and 33 +/- 0.6%; P less than 0.05). Also, the percentage of juxtaglomerular apparatuses (JGAs) containing renin or renin mRNA was higher in HP-fed rats (80 +/- 1.6 and 72 +/- 2%, respectively), than in NP-fed rats (46 +/- 2.2 and 40 +/- 4%; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415572 TI - Renal hemodynamic actions of lipoxins in rats: a comparative physiological study. AB - Interactions between either the arachidonate 5-lipoxygenase (5-LO) and 15-LO or 5 LO and 12-LO can lead to the formation of lipoxins. Although the functional significance of lipoxygenase products of arachidonic acid has been recognized increasingly in glomerular inflammation, less is known regarding the specific effects of lipoxins on renal hemodynamics. Here, we examine the renal actions of lipoxin (LX) A4, LXB4, and, the recently identified 7-cis-11-trans-LXA4, which were administered into the renal artery of the euvolemic male Munich-Wistar rat. LXA4 caused increases in renal plasma flow (RPF) and glomerular filtration rate (GFR) in a dose-dependent manner. These effects were reversed during cyclooxygenase inhibition. LXB4 decreased both RPF and GFR, and its mode of action was independent of cyclooxygenase activity. 7-cis-11-trans-LXA4 decreased RPF and GFR, which effects were abolished during systemic infusion of the leukotriene D4 receptor antagonist SKF 104353. Results indicate that each of these lipoxins displays distinct hemodynamic effects via a specific mode of action on the renal vasculature of rats. Moreover, they suggest mechanisms whereby lipoxins may participate in the changes of renal hemodynamics that occur during glomerular inflammatory processes. PMID- 1415574 TI - Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter. AB - We have used low-stringency screening with the human intestinal Na(+)-glucose cotransporter SGLT1 to isolate a 2,271-nucleotide cDNA (Hu14) from human kidney. This clone, which encodes a 672-residue protein, is 59% identical at the amino acid level to SGLT1 and has a similar number and arrangement of predicted membrane-spanning regions. It also shares significant sequence identity with other Na(+)-coupled transporters. Northern blot analysis suggests strong expression of Hu14 in kidney, but, unlike SGLT1, no significant expression in intestine. We have been unable to demonstrate definitive transport of any of a number of substrates (including amino acids, sugars, nucleosides, and vitamins) into Hu14 cRNA-injected Xenopus oocytes, although sequence conservation makes it likely that Hu14 represents another member of the Na+ cotransporter family, possibly a second Na(+)-glucose cotransporter. PMID- 1415573 TI - Potassium conductance regulation by pH during volume regulation in rabbit proximal convoluted tubules. AB - When rabbit proximal convoluted tubules were microperfused in the presence of bicarbonate, a 90 mosmol hypotonic shock hyperpolarized the basolateral membrane by 5.5 +/- 1.4 mV, increased basolateral potassium selectivity (tK) from 0.30 +/- 0.02 to 0.45 +/- 0.02, and reduced the basolateral membrane resistance from 4,887 +/- 821 to 2,836 +/- 602 omega.cm. These data show that the hypotonic shock increased absolute basolateral potassium conductance. The same hypotonic shock elevated intracellular pH from 7.18 +/- 0.04 to 7.31 +/- 0.04. When bath pH was increased by 0.2 pH units (by reduction of CO2), intracellular pH rose by 0.13 +/ 0.01. In separate experiments this maneuver hyperpolarized the basolateral membrane by 5.0 +/- 0.8 mV and augmented basolateral tK from 0.58 +/- 0.06 to 0.68 +/- 0.04, suggesting that the basolateral potassium conductance is sensitive to pH changes of a magnitude similar to that evoked by a hypotonic shock. In the nominal absence of bicarbonate or presence of 0.5 mM 4-acetamido-4' isothiocyanostilbene-2,2'-disulfonic acid (SITS) in the bath, the hypotonic shock caused a transient intracellular acidification, suggesting involvement of basolateral bicarbonate transport in the hypotonic shock-induced alkalinization. In the absence of bicarbonate, the hypotonic shock did not increase basolateral tK or induce hyperpolarization of the basolateral membrane. We conclude that the increase in potassium conductance observed during hypotonic shock is at least partly mediated by a bicarbonate-dependent, SITS-sensitive intracellular alkalinization. PMID- 1415575 TI - Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat glomeruli. AB - The effects of reactive oxygen species (ROS) on cultured rat mesangial cells were studied by measuring planar cell surface area (PCSA) after incubation with xanthine plus xanthine oxidase (XXO), in the presence of superoxide dismutase (SOD; 5 micrograms/ml) or catalase (CAT; 20 micrograms/ml), or after incubation with H2O2. Myosin light chain (MLC) phosphorylation was assessed in cells prelabeled with o-[32P]phosphoric acid and incubated with H2O2, after protein separation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible intermediate role for platelet-activating factor (PAF) was analyzed by preincubation of the cells with a PAF antagonist BN 52021 (BN, 5 x 10(-5) M) and by measuring PAF-specific [3H]acetate incorporation and immunoassayable PAF. XXO significantly decreased PCSA (14%), an effect abolished by CAT but not by SOD. H2O2 induced a similar effect, in a dose-dependent and time-dependent manner. MLC phosphorylation increased by 81 +/- 15% after H2O2 incubation, and this effect was blocked by BN. BN also completely blocked the effect of H2O2 on PCSA. PAF specific [3H]acetate incorporation increased in the presence of H2O2 (from 6,886 +/- 2,030 to 58,703 +/- 16,063 counts.min-1.mg-1) as well as the immunoassayable PAF production by cells (from 0.90 +/- 0.19 to 6.71 +/- 2.27 ng/mg). These results suggest that ROS, particularly H2O2, could modulate the surface area of mesangial cells, modifying the ultrafiltration coefficient, thus explaining the decrease in glomerular filtration rate in those pathological situations characterized by an increased ROS synthesis. PAF could be involved in the genesis of these effects. PMID- 1415576 TI - Feedback modulation of renal and hepatic erythropoietin mRNA in response to graded anemia and hypoxia. AB - Erythropoietin (EPO) mRNA levels were measured by ribonuclease (RNase) protection in organs from unstimulated rats and from animals after normobaric hypoxia or hemorrhagic anemia. Both liver and kidney responded to stimulation with large increases in EPO mRNA, but the response characteristic to graded stimulation was different. The liver responded poorly to mild normobaric hypoxia, accounting for only 2 +/- 1% of total EPO mRNA at 11% O2, but hepatic EPO mRNA levels increased steeply with more severe hypoxia so that at 7.5% O2 the liver contributed to 33 +/- 7% of the total. After hemorrhagic anemia, the liver also responded more strongly to more severe stimulation, but at all points it accounted for a significant proportion of total EPO mRNA, contributing 18 +/- 6% after removal of 2.5 ml (hematocrit 37.2 +/- 1.3%), increasing to 37 +/- 14% after venesection of 10.5 ml (hematocrit 15.8 +/- 0.8%). Studies of EPO mRNA in other organs confirmed that EPO production outside the liver and kidney were quantitatively insignificant in stimulated animals. However, the hypoxia-induced increases in EPO mRNA in brain, testis, and spleen suggest the existence of an oxygen-sensing mechanism at other sites. PMID- 1415577 TI - Effects of adenosine on ion transport in rat medullary thick ascending limb. AB - Previously, we demonstrated that adenosine (Ado) was released by the medullary thick ascending limb (MTAL) during hypoxia. The present experiments were designed to examine the effects of Ado and adenosine analogues on net chloride (JCl) and bicarbonate (JHCO3) absorption by the isolated, perfused MTAL of the rat. Ado, 10 nM, in the presence or absence of arginine vasopressin (AVP, 10(-10) M) reduced JCl by 50%. The inhibition of Ado was reproduced with the selective A1 agonist, N 6-phenylisopropyladenine (2 nM), and was reversed by 8-cyclopentyl-1,3 dipropylxanthine, an A1-receptor antagonist. Thus the inhibition of JCl is likely mediated through A1 receptors. In contrast, Ado had no effect on (JHCO3) either in the presence or absence of AVP. Ado also had no influence on the effect of AVP to inhibit JHCO3. The lack of effect on JHCO3 suggests that the inhibition of JCl by Ado is unlikely to be mediated through changes in cellular adenosine 3',5' cyclic monophosphate. These results support the hypothesis that Ado released into the renal medulla during hypoxia may protect the MTAL from ischemic injury by directly inhibiting NaCl absorption and reducing transport-related oxygen consumption. PMID- 1415578 TI - Renal injury in obese Zucker rats: glomerular hemodynamic alterations and effects of enalapril. AB - Angiotensin-converting enzyme inhibitors may ameliorate experimental glomerular injury by either hemodynamic or nonhemodynamic mechanisms. In a long-term study, we examined the effects of 30 wk of enalapril treatment on the development of glomerular disease in obese Zucker rats (OZR). Enalapril significantly (P less than 0.05) lowered blood pressure, fasting serum cholesterol, and urine albumin excretion in OZR throughout the experimental period. At 38 wk of age, enalapril treated OZR had a sixfold reduction in the percent glomeruli exhibiting focal glomerulosclerosis and a 20-30% reduction in kidney weight and glomerular area. A separate micropuncture study in 22- to 26-wk-old rats revealed that untreated OZR with albuminuria and increased blood pressure had elevated glomerular capillary pressure (Pgc). Enalapril-treated OZR had less albuminuria and lower blood pressure, but Pgc was not reduced. The value of the transcapillary hydraulic pressure difference (delta P) in enalapril-treated OZR was intermediate between values in untreated OZR and lean Zucker rats. Thus enalapril markedly attenuated the development of glomerular injury in OZR. The salutary effects of enalapril may have involved a reduction in delta P coupled to a nonhemodynamic action, possibly restriction of glomerular growth or lowering of serum cholesterol. PMID- 1415579 TI - Critical role of bicarbonate in calcium release from bone. AB - Calcium release from cultured bone is pH dependent; net calcium flux (JCa) from bone increases with decreasing pH. At a similar decrement in pH there is greater JCa when acidosis is produced by a low medium bicarbonate concentration ([HCO3 ]), a model of metabolic acidosis (Met), compared with an increased medium PCO2, a model of respiratory acidosis (Resp). To separate the role of [HCO3-] from that of pH in inducing JCa we cultured calvariae for 3 h under three different neutral (pH approximately 7.4) isohydric environments [control (Ctl), fully compensated Met (C-Met), or fully compensated Resp (C-Resp)] and two different acid (pH approximately 7.1) isohydric environments (Met or Resp). During neutral pH (Ctl, C-Met, and C-Resp) there was JCa from bone during C-Met (decreased [HCO3-]), no net flux during Ctl (normal [HCO3-]), and JCa into bone during C-Resp (increased [HCO3-]); and JCa was correlated inversely with [HCO3-] (r = -0.824, n = 36, P less than 0.001). During acid pH there was greater JCa from bone during Met (decreased [HCO3-]) than during Resp (normal [HCO3-]); and JCa was again correlated inversely with [HCO3-] (r = -0.848, n = 22, P less than 0.001). JCa from bone during Met and Resp was greater than C-Met and C-Resp, respectively. The addition of the osteoclastic inhibitor salmon calcitonin did not alter the relative JCa results. Thus at a constant pH the magnitude of JCa from cultured neonatal mouse calvariae appears dependent on the [HCO3-]; the lower the [HCO3-], the greater the calcium efflux.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415580 TI - Induction of water diuresis by endothelin in rats. AB - Experiments were performed in anesthetized rats to examine the possibility that endothelin (ET) modifies renal epithelial function in addition to its well established hemodynamic actions. Infusion of ET-3 at rates between 34 and 178 ng.kg-1.min-1 was in many cases followed by a rise in urine flow and a persistent decrease in urine osmolality, whereas glomerular filtration rate (GFR) did not significantly change. The extent of ET-induced diuresis was dependent on the response of GFR: in rats in which ET-3 infusion caused a marked reduction of GFR (greater than 70%) ET-induced diuresis was not seen, even though urine osmolality still fell significantly. From animal to animal, ET-induced changes of urine flow or GFR did not correlate significantly with the rate of ET-3 infusion. ET-1, another ET isopeptide, also produced water diuresis when administered in GFR neutral doses. Urinary excretion of total solutes and of sodium was not significantly altered by ET-3. Infusion of vasopressin blunted the diuretic effect of ET-3, whereas ET-3-induced water diuresis was not measurably altered by chronic or acute treatment with a converting enzyme inhibitor or by acute inhibition of prostaglandin synthesis. Induction of water diuresis was not secondary to an inhibition of vasopressin secretion since it could be demonstrated in homozygous Brattleboro rats in which antidiuresis was produced by the infusion of vasopressin at a rate of 200 microU.kg-1.min-1. These data suggest that ET may be an inhibitory modulator of the hydrosmotic action of vasopressin at the level of the renal collecting duct. PMID- 1415581 TI - Enhanced intrarenal angiotensin II generation in response to obstruction of the pig ureter. AB - The effect of acute unilateral complete ureteral obstruction (UUO) on renal hemodynamics has been examined in a pig model. Pigs were operated on under general anesthesia, electromagnetic flow probes were inserted around renal arteries, and catheters were implanted in renal veins and aorta for blood sampling. The influence of 15 h of obstruction on the physiological variation in immunoreactive angiotensin II (ANG II) was measured together with detailed analysis of the renal handling of ANG II in anesthetized animals. Pelvic pressure rose significantly within 2 h to a maximum of 59.9 +/- 2.9 cmH2O (n = 10). The ipsilateral renal blood flow (RBF) was reduced by 30% from 319 +/- 35 to 241 +/- 42 ml/min (P = 0.001), whereas contralateral RBF did not change. A temporary significant increase in mean aortic blood pressure was seen during the first 2 h after UUO. Renal vascular resistance increased by 44% in the obstructed kidney from 37 +/- 3 to 55 +/- 9 mmHg.ml-1.min.g during the course of obstruction. Concomitantly, the plasma concentration of immunoreactive ANG II increased from all three sample sites by 8-15 times. This increase was highly significant compared with the sham-operated group. The results show that the pig kidney responds to UUO by a net secretion of ANG II from the ipsilateral kidney. Our observations on the ANG II renal secretion rate suggest that part of the immunoreactive ANG II in the renal venous effluent originated de novo from intrarenal generation. PMID- 1415582 TI - Effect of cyclooxygenase inhibition on renal blood flow autoregulation in SHR. AB - The effect of acute and chronic indomethacin treatment on renal blood flow (RBF) autoregulation was studied in 10- and 40-wk-old spontaneously hypertensive rats (SHR). RBF autoregulation was substantially reduced in 40-wk-old SHR both during acute and chronic indomethacin treatment, whereas no effect was seen in the young SHR. The pressure range of autoregulation was 169 +/- 9 to 130 +/- 5 mmHg in the untreated 40-wk-old SHR, and 154 +/- 14 to 146 +/- 6 mmHg in indomethacin-treated 40-wk-old SHR (P less than 0.001). Indomethacin treatment had no effect on control RBF, mean arterial pressure, or renal vascular resistance in the 40-wk old SHR. After removal of the renal nerves, RBF autoregulation during indomethacin treatment was restored in 40-wk-old SHR. The pressure range of RBF autoregulation was 158 +/- 7 to 142 +/- 7 mmHg in sham-operated animals, significantly different from the denervated 40-wk-old SHR, where RBF was autoregulated from 150 +/- 5 to 118 +/- 6 mmHg (P less than 0.01) during indomethacin treatment. The afferent arteriolar diameter (DAA) was studied by the microsphere method in 10-wk-old SHR and in untreated and indomethacin-treated 40 wk-old SHR. DAA was significantly greater in 40-wk-old compared with 10-wk-old SHR (22.1 +/- 0.4 vs. 17.9 +/- 0.5 microns) (P less than 0.01), whereas indomethacin treatment in 40-wk-old SHR did not influence the DAA significantly (21.5 +/- 0.3 microns, P greater than 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415583 TI - Beta 2-microglobulin induces calcium efflux from cultured neonatal mouse calvariae. AB - beta 2-Microglobulin (beta 2M) polymerizes to form amyloid fibrils that deposit and cause destructive bone lesions in patients on chronic dialytic therapy. beta 2 M is mitogenic to osteoblasts; however, its effect on bone mineralization is unknown. To determine whether beta 2M causes bone demineralization, neonatal mouse calvariae were incubated with and without beta 2M, and net calcium flux was calculated. Following a 48-h but not 3- or 24-h incubation, beta 2M (10(-8)-10( 6) M) induced a net calcium efflux. The efflux was similar to that observed with 10(-10) M parathyroid hormone (PTH) but less than that observed with 10(-8 M PTH. Devitalizing the calvariae resulted in a net calcium influx that was unaffected by the addition of beta 2M, indicating a cell-mediated phenomenon. The release of beta-glucuronidase, an osteoclast enzyme, increased after a 48-h but not a 24-h incubation with beta 2M. Calcitonin, an osteoclast inhibitor, blocked the beta 2M induced calcium efflux and beta-glucuronidase release, suggesting osteoclast involvement. Thus beta 2M induces a dose- and time-dependent, cell-mediated calcium efflux from neonatal mouse calvariae that involves osteoclast stimulation. PMID- 1415584 TI - Clearance receptor and neutral endopeptidase-mediated metabolism of atrial natriuretic factor. AB - A novel small linear C-atrial natriuretic factor receptor ligand [C-ANF-(11-15)] and phosphoramidon (PHO) were used to determine the effects of C-ANF receptor blockade alone, or in combination with inhibition of neutral endopeptidase (NEP), on the pharmacokinetics and metabolism of ANF in the rat. C-ANF-(11-15) infusion decreased apparent volume of distribution (Vss) and metabolic clearance rate (MCR) of administered 125I-ANF-(1-28) to one-third of their control values, whereas PHO alone was without effect on these parameters. In combination with C ANF-(11-15), however, PHO further decreased MCR of 125I-ANF-(1-28) and increased plasma half time by more than threefold. High-performance liquid chromatography analysis revealed that C-ANF-(11-15) inhibited the delayed appearance of free 125I and [125I]monoiodotyrosine but had no effect on the small proportion of NEP metabolites in plasma. The combination of C-ANF-(11-15) and PHO further delayed the appearance of small metabolites, abolished the appearance of NEP metabolites, and markedly prolonged the permanence of intact 125I-ANF-(1-28) in plasma. The results demonstrate that C-ANF receptor blockade by C-ANF-(11-15) impairs clearance and metabolism of ANF, an effect which is synergistically potentiated by concomitant inhibition of NEP. C-ANF-(11-15) alone or in combination with NEP inhibitors may be a potentially useful therapeutic tool in the treatment of cardiovascular and renal diseases. PMID- 1415585 TI - Calorie restriction decreases microalbuminuria associated with aging in barrier raised Fischer 344 rats. AB - Renal function as a sensitive biomarker of aging has been studied in specific pathogen-free (SPF) Fischer 344 rats (n = 211), and results are presented according to animal age (5, 8, 12, 18, 24 mo), sex, and diet (ad libitum vs. 40% calorie restriction). Plasma creatinine concentration, endogenous creatinine clearance, total protein excretion, and albumin excretion were measured. Kidney histology was evaluated by light microscopy. In both calorie-restricted and ad libitum-fed animals, kidney weight (KW) and body weight (BW) showed parallel changes with age. The KW-to-BW ratio was unaffected by age in all groups. There was no alteration in plasma creatinine concentration as a function of age or diet. In these SPF animals there was also no change in glomerular filtration rate with age. In animals fed ad libitum, albumin and protein excretion increased with age (females: 0.39 +/- 0.05 at 5 mo vs. 7.4 +/- 2.6 mg protein.24 h-1.g KW-1 at 24 mo; males: 4.1 +/- 0.6 at 5 mo vs. 15 +/- 3 mg protein.24 h-1.g KW-1 at 24 mo). The higher protein excretion rate in all males at 5 mo reflected the excretion of sex-dependent low-molecular-weight proteins that commenced with sexual maturation. Calorie restriction prevented the age-dependent increase in total protein excretion. Kidney histopathology was positively correlated with total protein and albumin excretion. Microalbuminuria preceded the development of lesions detectable by light microscopy. These observations support the concept that microalbuminuria in this model is a sensitive and early biomarker of nephropathy that can be monitored easily and noninvasively. PMID- 1415586 TI - Three-dimensional reconstructed glomerular capillary network: blood flow distribution and local filtration. AB - We developed a mathematical model to simulate blood flow and filtration in individual capillary segments of a glomerular network reconstructed from a normal Munich-Wistar (MW) rat. Three-dimensional geometric reconstruction was obtained by semithin serial sections (1 micron) of one glomerulus after perfusion fixation of kidney. Photomicrographs of each section were digitized and processed, using a computer-based image-analysis system, to derive the topological organization of the capillary network and mean diameter and length of individual capillary segments. Blood flow rate in capillary segments was calculated using a theoretical model that considers apparent viscosity of blood in small capillaries as a function of local rheological parameters, partition of cells at bifurcations, and local filtration dependent on transmembrane hydraulic and oncotic pressure gradients along the network. In accord with previous observations, the topological organization of the capillary network disclosed a three-lobular structure. The ultrafiltration coefficient (Kf) calculated for the euvolemic MW rat with the present network approach was compared with that derived from a theoretical model that assumes identical capillaries in parallel. The latter model is shown to underestimate Kf, particularly under conditions in which filtration pressure equilibrium is approached. Calculation of local blood flow and filtration along the network indicates a heterogeneous distribution of these parameters and that some parts of the capillary network operate at filtration pressure equilibrium even if the overall network operates at filtration disequilibrium. PMID- 1415587 TI - Cellular mechanisms involved in the vascular myogenic response. AB - By definition, the myogenic response is the contraction of a blood vessel that occurs when intravascular pressure is elevated and, conversely, the vasodilation that follows a reduction in pressure. Over the last several decades numerous investigators have demonstrated the importance of the myogenic response in the local regulations of blood flow, capillary pressure, and in the generation of basal vascular tone. Despite the considerable information obtained from these investigations, information about the cellular mechanisms that underlie this response has been slow to accumulate. Because of the physiological significance of the myogenic response, its mechanistic basis represents an important subject for research. Currently, there are several broad hypotheses concerning the sequence of events that couple changes in intravascular pressure or stretch with alterations in vascular smooth muscle activation. These hypotheses include 1) altered membrane properties leading to activation of ion channels; 2) modulation of biochemical cell-signaling pathways within vascular smooth muscle; 3) length dependent changes in contractile protein function; and 4) endothelial-dependent modulation of vascular smooth muscle tone. This review summarizes current work relative to each of these hypotheses and describes a possible sequence of events to account for myogenic activation of vascular smooth muscle. PMID- 1415588 TI - Effects of a novel prostaglandin, 8-epi-PGF2 alpha, in rabbit lung in situ. AB - We determined the effects of 8-epiprostaglandin (PG) F2 alpha, a noncyclooxygenase free radical-catalyzed product of arachidonic acid, on pulmonary vascular tone, its potency, and its mechanism of action. 8-Epi-PGF2 alpha (0.5-20 micrograms) was injected into the pulmonary artery (PA) catheter of 10 rabbits whose lungs were perfused in situ with Krebs-Henseleit buffer solution with 3% bovine serum albumin. PA pressure increased from a baseline of 13.5 +/- 0.6 to 25.6 +/- 2.0 cmH2O with 20 micrograms 8-epi-PGF2 alpha. 8-Epi-PGF2 alpha caused a rapid rise in PA pressure followed by a gradual decline over 40-60 min to baseline levels. Double vascular occlusion revealed a twofold increase in arterial resistance at peak rise in PA pressure. The rise in PA pressure with 20 micrograms 8-epi-PGF2 alpha was fivefold greater than with 20 micrograms of the cyclooxygenase-derived prostaglandin PGF2 alpha. The PA pressure response to 8 epi-PGF2 alpha was not altered by either cyclooxygenase block-ade with 150 microM meclofenamate or alpha-receptor blockade with 70 microM phentolamine, but was fully prevented by 40 microM SQ 29548, a thromboxane receptor antagonist. We conclude that in rabbits 8-epi-PGF2 alpha is a potent vasoconstrictor of the pulmonary vasculature, which appears to be due to the activation of SQ 29548 responsive thromboxane receptors. PMID- 1415589 TI - Salt intake and angiotensin II alter microvessel density in the cremaster muscle of normal rats. AB - This study investigated the effect of salt intake and angiotensin II (ANG II) levels on microvessel density (MVD). Rats with indwelling arterial and venous catheters were placed on either a high-salt (HS; 4%) or a low-salt diet (LS; 0.4%) for 2 or 4 wk, and blood pressure, heart rate, and plasma renin activity were measured. Plasma ANG II was fixed at normal levels in half of the rats on HS by continuous intravenous infusion of ANG II (5 ng.kg-1.min-1). Samples of cremaster muscle were examined histologically to determine MVD. No difference in MVD was observed between HS and LS groups after 2 wk. After 4 wk on HS, MVD was reduced (22.4%, P less than 0.05) compared with the LS group. In rats fed HS, ANG II infusion induced a significant dose-dependent increase in MVD from 85.11 +/- 3.34 to 98.94 +/- 4.62 (ANG II, 5 ng.kg-1.min-1) and to 107.60 +/- 7.00 (ANG II, 10 ng.kg-1.min-1) (P less than 0.05), with no change in blood pressure. Maintenance of ANG II levels for 4 wk blocked the rarefaction due to salt. These results suggest that the decrease in MVD due to salt could be the result of a dietary-induced fall in plasma ANG II levels. PMID- 1415590 TI - Tumor necrosis factor challenges in canines: patterns of cardiovascular dysfunction. AB - Three groups of conscious canines were given different intravenous doses of human recombinant tumor necrosis factor (TNF) over 1 h, and the resulting cardiovascular abnormalities were examined for 10 days. As TNF dose increased [0 (controls), 30, 60, and 120 micrograms/kg body wt], the number of deaths increased (P less than 0.025; 0 of 6, 1 of 8, 4 of 8, number of deaths in each group, respectively). In all three groups receiving TNF, the mean left ventricular ejection fraction (LVEF) at 2 h after infusion decreased (P less than 0.003) compared with controls. The group receiving the highest dose of TNF (120 micrograms/kg body wt) had the greatest decrease (P less than 0.05) in LVEF from 0 to 2 h. At 8 h, all three groups receiving TNF had similar LVEF. In these three groups, other multiple measures of LV function at 8 h showed significant and similar decreases in cardiac contractility compared with controls. From 24 to 240 h, however, the time required for cardiac performance (LVEF) to return to normal was dose dependent (30 less than 60 less than 120 micrograms/kg body wt; P less than 0.05). Canines receiving the lowest dose of TNF had near normal cardiac function (LVEF) at 24 h, whereas canines receiving the highest dose had persistent cardiac abnormalities at 240 h. Thus, at 8 h, the severity of cardiac dysfunction is independent of TNF dose, but the rate of onset and the duration of cardiac abnormality are markedly dependent of dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415591 TI - Bioassay of endothelium-derived relaxing factor in diabetic rat aorta. AB - The bioassay technique was utilized to quantitate endothelium-derived relaxing factor (EDRF) released from perfused donor segments of control and diabetic rat aorta. In the presence of indomethacin, perfusates of donor segments with endothelium were allowed to superfuse recipient detector rings of normal rat aorta without endothelium. Under basal conditions, relaxations of the bioassay rings to perfusates of control and diabetic donor segments were similar. Perfusion of donor segments with acetylcholine produced relaxation of bioassay rings, which was decreased from endothelial perfusion of diabetic donor segments. These relaxations were inhibited by addition of methylene blue to the detector ring or by perfusion of donor segments with nitro-L-arginine. Infusion of superoxide dismutase (SOD) at a site proximal to the donor segment normalized relaxations induced by acetylcholine addition to diabetic donors. In contrast, infusion of SOD distal to the donor had no effect on acetylcholine-stimulated relaxations of detector rings from control donors while attenuating, paradoxically, the relaxations of detector rings from diabetic donors. These results suggest that diabetic rat aortas release similar levels of EDRF in response to acetylcholine, but the action of EDRF arising from diabetic donors is attenuated by enhanced release of oxygen-derived free radicals, which limits EDRF mediated relaxation of vascular smooth muscle. PMID- 1415593 TI - Recovery of arterial pressure control after partial baroreceptor denervation in awake rabbits. AB - We examined recovery of control of heart rate (HR) and total peripheral resistance (TPR) by arterial baroreceptors after bilateral carotid sinus and aortic denervation or unilateral carotid sinus and aortic denervation in conscious rabbits. In one group of animals, HR responses to changes in mean arterial pressure (MAP) after injection of nitroglycerin or phenylephrine were measured in control studies and at 2, 5, 10, and 15 days after partial baroreceptor denervation. All denervation procedures increased MAP and HR at 2 and 5 days after denervation. Reflex sensitivity decreased to 57-67% of control on day 2 after denervation. HR responses recovered by day 10 after bilateral aortic or carotid sinus denervation; however, recovery following unilateral denervation was less complete. In a second group of animals, studied after implantation of aortic flowmeters, TPR changes following reduction in cardiac output by inferior vena caval occlusion were 49% of control responses on day 2 after denervation and returned close to control level on day 5. Controls of HR and TPR recovered substantially and were not significantly different from control 10 days after partial denervation. Recovery apparently occurred through the remaining arterial baroreceptors, possibly due to central reorganization of reflex pathways. PMID- 1415592 TI - Increased oxyhemoglobin affinity by carbamylation: coronary autoregulation and O2 transport. AB - Hemoglobin carbamylation with sodium cyanate was used to study myocardial O2 delivery during increased oxyhemoglobin affinity. A group of control dogs was compared with a group of dogs, in which their hemoglobin had been carbamylated by daily ingestion of sodium cyanate over a period of 6-8 wk. The O2 tension at 50% saturation of hemoglobin (P50) averaged 23 mmHg in the carbamylated group compared with an average P50 of 31 mmHg in the control group. The left main coronary artery was cannulated and perfused via an extracorporeal, pressure controlled reservoir. Coronary pressure, coronary flow, and blood gas measurements were made at coronary perfusion pressures spanning the autoregulatory range. The increased oxyhemoglobin affinity produced no significant difference in convective O2 transport to the coronary capillaries, although the carbamylated group had a significantly higher arterial O2 content and significantly lower coronary flow. The autoregulatory process was not significantly altered by carbamylation-induced shifts in the O2 dissociation curve. Despite a significantly lower coronary sinus PO2 in the carbamylated group, the increase in oxyhemoglobin affinity was associated with significantly lower O2 extractions in the carbamylated group. Significant extraction reserve was present in both the control and carbamylated groups as demonstrated by the fact that O2 extraction could still increase well above control levels when perfusion pressure was lowered. We conclude that there is no significant vasodilatory compensation for moderate increases in oxyhemoglobin affinity, despite the continued presence of autoregulatory vasodilatory reserve. PMID- 1415594 TI - Coronary microvascular response to endothelin is dependent on vessel diameter and route of administration. AB - Endothelin is a 21-amino acid peptide originally isolated from vascular endothelial cells. In the present study, we examined the effect of topical and intracoronary administration of endothelin-1 on the coronary microcirculation and the effect of inhibition of cyclooxygenase on the microvascular response to intracoronary endothelin. In anesthetized dogs (n = 39), the coronary microcirculation was visualized using stroboscopic epi-illumination synchronized to the cardiac cycle. Topical application of endothelin [(5 x 10(-9) to 10(-8) M] constricted all arteries and arterioles with the degree of constriction inversely related to vessel size. Coronary veins and venules did not constrict to endothelin. Topical application of EDTA (10 mg/ml) reversed the constriction to endothelin in arterioles of all sizes. In contrast, intracoronary administration of endothelin (10(-8) to 10(-7) M) produced dilation of small arterioles (less than 130 microns) and no response of large arterioles (greater than 130 microns). The response of small arterioles to intracoronary endothelin was not altered by inhibition of cyclooxygenase with indomethacin (5 mg/kg); however, large arterioles constricted. Thus the coronary microvascular response to endothelin is dependent on the route of administration. Constriction of arteries and arterioles of all sizes to endothelin is dependent on extracellular calcium. Vasodilator prostaglandins may be released in response to intracoronary administration of endothelin predominantly in larger vessels. Thus the differential response to endothelin with topical and intracoronary administration may reflect a diffusional barrier of the endothelium or release of endothelium-derived relaxing factor and prostaglandins in response to endothelin. PMID- 1415595 TI - Norepinephrine increases the economy of pressure development in isolated canine hearts. AB - To test for oxygen wasting by norepinephrine (NE) without relying on normalization by measures of performance such as the pressure-volume area, myocardial oxygen consumption (MVO2) was determined for isovolumic beats at five different left ventricular (LV) end-diastolic volumes (EDV) in nine isolated cross-perfused canine hearts in each of three states: a basal anesthetic state (B); after depression with halothane (H); and after adding NE to increase contractility back to the B state (H+NE). The end-diastolic and peak systolic pressure-volume lines were identical for B and H+NE. The R2 for a linear regression of MVO2 per beat for B vs. H+NE for beats originating at the same EDV and developing similar (within 10%) peak isovolumic pressures for all hearts was 0.85. The slope and intercept were 0.83 and 0.01, which are significantly less than one (P less than 0.001) and greater than zero (P less than 0.001), respectively. These data suggest that NE increases both the economy of pressure development as well as activation energy of an isovolumically contracting LV. PMID- 1415596 TI - Dexamethasone-induced differentiation of atrial myocytes in culture. AB - Atrial and ventricular myocytes from fetal and newborn rats were cultured in medium supplemented with fetal or newborn calf serum with and without glucocorticoid. Myocyte morphology was examined by light and electron microscopy, and the amount of stored and secreted atrial natriuretic peptide (ANP) was measured. Without dexamethasone, neonatal atrial myocytes cultured for 7 days contained myofibrils organized into sarcomeres and numerous endocrine granules containing immunostainable ANP. Secretion of immunoreactive ANP reached a peak between days 7 and 9 of culture. Myocytes from fetal rats secreted ANP but contained few endocrine granules, and myofilaments were poorly organized. By contrast, the addition of dexamethasone (1 nM-1 microM) to the culture medium of newborn myocytes promoted development of numerous endocrine storage granules, mitochondria, and myofibrils with prominent Z-bands. Dexamethasone also increased the cellular content of ANP and ANP-specific mRNA in both atrial and ventricular myocytes. In the presence of dexamethasone myocytes maintained their structural integrity for periods of at least 45 days. PMID- 1415597 TI - Fluorochemical emulsion APE-LM substantially improves cardiac preservation. AB - We determined the efficacy of a novel fluorochemical emulsion for long-term hypothermic preservation of hearts. Rat hearts were preserved for 12 h at 12 degrees C with use of continuous low-pressure coronary perfusion with one of three oxygenated media (n = 6 hearts/groups): an "extracellular" crystalloid solution; APE-LM, a novel fluorochemical emulsion of perfluoroperhydrophenanthrene in egg yolk phospholipid; and FC-43, the Fluosol-43 (Oxypherol) fluorochemical emulsion of perfluorotributylamine in Pluronic F68. The emulsion media contained the same components as the crystalloid medium. All three media contained 0.5% albumin. An isolated working heart perfusion system was used to quantify the function of preserved hearts and controls (fresh hearts, n = 6). The APE-LM-preserved hearts were not significantly different from control hearts in contractile function, output, and energetics during a 4-h 37 degrees C reperfusion period. The control and APE-LM-preserved hearts had significantly better performance than crystalloid- and FC-43-preserved hearts. All preserved hearts gained fluid during preservation. The edema of APE-LM-preserved hearts, but not that of the other two preserved groups, was reversed during 37 degrees C reperfusion. These data provide the first evidence that a unique fluorochemical emulsion improves long-term preservation of cardiac tissue and produces significantly better recovery of cardiac function after preservation. This salutary effect was specifically associated with APE-LM emulsion and may result from its high O2 capacity, its biologically compatible emulsifier, and its superior physical properties, which include very small emulsion particle size (0.1-0.15 micron), low viscosity, and minimal toxicity. PMID- 1415599 TI - EDRF plays central role in collateral flow after arterial occlusion in rabbit ear. AB - An in vitro model has been developed in which the acute development of collateral perfusion of a segment of rabbit central ear artery, isolated between ligatures, is assessed by X-ray microangiography. Collateral perfusion was quantified by normalizing the volume of the segment filled with respect to its preocclusion control. The influence of endothelium-derived relaxing factor (EDRF) activity on perfusion was examined by using 100 microM NG-nitro-L-arginine methyl ester (L NAME), a potent inhibitor of nitric oxide synthesis. Filling of the isolated segment after occlusion was time dependent, being 21.6 +/- 4.2% after 2 min and 46.6 +/- 5.3% after 90 min. This acute development of collateral flow was reversed by addition of L-NAME 60 min after ligation, after which filling was reduced to 17.8 +/- 3.8%. When L-NAME was added before ligation, filling of the segment was 15.6 +/- 5.9% at 2 min and 14.8 +/- 7.4% at 90 min, so that the time dependent component of collateral flow development was abolished. The inhibitory effects of L-NAME on collateral perfusion were reversed by an excess of L arginine. These findings indicate that EDRF plays a central role in the development and maintenance of collateral flow. PMID- 1415598 TI - Topical arachidonic acid restores pial arteriolar dilation to hypercapnia of postischemic newborn pig brain. AB - In the newborn pig, cerebral vasodilator responses to hypercapnia are lost after cerebral ischemia. We examined the effect of topical application of arachidonic acid (30 micrograms/ml, 20 min) to the postischemic piglet brain on subsequent pial arteriolar dilated in response to hypercapnia (10% CO2 ventilation) and topical isoproterenol (10(-6), 10(-7) M). After 20 min cerebral ischemia, pial arterioles did not dilate to hypercapnia but responded to isoproterenol in a fashion similar to before ischemia. Treatment with arachidonic acid after ischemia restored pial arteriolar dilation to hypercapnia. Hypercapnia caused an increase in cortical periarachnoid concentration of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) before but not after ischemia. After postischemic treatment with arachidonic acid, the increase in cortical periarachnoid fluid 6-keto-PGF1 alpha during hypercapnia was restored. Therefore, topical application of arachidonic acid to cerebral vessels restores cerebral prostanoid synthesis and pial arteriolar dilation in response to hypercapnia that has been abolished by ischemia. PMID- 1415600 TI - Differential effects of WEB 2086 and SRI 63-441 on TNF-alpha-induced alterations in cardiopulmonary function. AB - We hypothesized that platelet-activating factor (PAF) and cyclooxygenase products might be important mediators of the cardiopulmonary effects induced by tumor necrosis factor (TNF-alpha) in anesthetized pigs. A 6-h infusion of human recombinant TNF-alpha caused hypoxemia, leukopenia, thrombocytopenia, decreased cardiac index (CI), increased pulmonary vascular resistance (PVR) and increased mean pulmonary arterial (Ppa) and intratracheal (Pt) pressures. Administration of the PAF receptor antagonist SRI 63-441 or indomethacin blocked the early (0.25 0.5 h) and attenuated the later increases in PVR and Ppa; indomethacin also attenuated the increase in Pt and hypoxemia associated with TNF-alpha infusion. WEB 2086 did not attenuate the TNF-alpha-induced alterations in CI, PVR, Pt, or PaO2. The in vivo specificity of SRI 63-441 and WEB 2086 was tested by infusing exogenous PAF, prostaglandin (PG) F2 alpha, U-46619 [thromboxane (Tx)A2 receptor mimetic], or arachidonic acid (AA) before and during administration of SRI 63-441 or WEB 2086. Both antagonists blocked the cardiopulmonary effects induced by exogenous PAF. SRI 63-441, but not WEB 2086, significantly attenuated the increased PVR caused by PGF2 alpha, U-46619, and AA. We conclude that SRI 63-441 is a less specific PAF receptor antagonist in vivo compared with WEB 2086 and that cyclooxygenase products, but not PAF, contribute significantly to the cardiopulmonary responses induced by exogenously infused TNF-alpha in pigs. PMID- 1415601 TI - Beneficial effects of SPM-5185, a cysteine-containing NO donor in myocardial ischemia-reperfusion. AB - Intravenous administration of SPM-5185 [N-nitratopivaloyl-S-(N'-acetylalanyl) cysteine ethyl ester], a cysteine-containing nitric oxide (NO) donor, or SPM-5267 [pivaloyl-S-(N'-acetylalanyl)-cysteine ethyl ester], an analogue of SPM-5185 that lacks the NO moiety, was studied in a feline myocardial ischemia-reperfusion model. Administration of SPM-5185 (1 mg/kg), followed by a 2-mg.kg-1.h-1 infusion starting 10 min before reperfusion, resulted in significant protection 4.5 h postreperfusion. In the myocardial ischemia (MI)+SPM-5267 group, 38 +/- 4% of the area at risk was necrotic, whereas the necrotic area/area at risk was only 7 +/- 2% in the MI+SPM-5185 group (P less than 0.01). Moreover, SPM-5185 treatment markedly attenuated the endothelial dysfunction observed in the left anterior descending coronary artery after reperfusion by 50%. These beneficial effects occurred despite the absence of a significant change in myocardial oxygen demand, as measured by the pressure-rate index. In vitro experiments demonstrated that SMP-5185, but not SPM-5267, decreased adherence of neutrophils to the coronary vascular endothelium and decreased production of superoxide radicals. Therefore, a likely mechanism of the observed cardioprotection by SPM-5185 involves attenuation of polymorphonuclear leukocyte-induced endothelial dysfunction. PMID- 1415602 TI - Aging- and training-induced alterations in collagen characteristics of rat left ventricle and papillary muscle. AB - We evaluated the single and interactive effects of aging and exercise training on selected parameters of myocardial interstitium in both the left ventricle (LV) and LV papillary muscle of female Fischer 344 specific pathogen-free rats. Ten weeks of treadmill running resulted in significant LV hypertrophy as well as elevated plantaris muscle citrate synthase activity in both young adult (5-mo old) and senescent (23-mo-old) trained animals (YT, young trained; OT, old trained) compared with age-matched sedentary controls (YC, young control; OC, old control). Proline and hydroxyproline pools were significantly higher (both P less than 0.05) in 23-mo-old vs. 5-mo-old papillary muscles. Degree of maturation (nonreducible cross-linking) of LV collagen was evaluated by measurement of hydroxylysylpyridinoline concentration ([HP]). In a comparison of YC with OC rats, ventricular [HP] increased approximately fivefold from 0.059 +/- 0.007 to 0.285 +/- 0.018 (SE) mol HP/mol collagen (P less than 0.001). Whereas training had no effect on ventricular [HP] in young adult rats, it significantly reduced LV collagen cross-linking in OT rats (0.131 +/- 0.027) so that HP values in this group were less than one-half of those observed in OC rats. Because both collagen concentration and degree of cross-linking are thought to affect muscle stiffness characteristics, we conclude that the observed changes should be considered in any explanation for aging- and training-induced alterations in LV and papillary muscle contractile indexes. PMID- 1415604 TI - Saline diuresis and natriuresis in unanesthetized dogs: a missing atrial factor? AB - Recent studies in our laboratory indicated that a blunted (40-50%) renal excretory response to isotonic intravenous saline loads occurred in conscious, renal-denervated dogs after 70% of the atrial mass was removed. The blunted responses could not be explained by differences in the responses of arterial pressure, renal nerve activity, or by measured changes of plasma immunoreactive atrial natriuretic peptide (iANP), arginine vasopressin (AVP), plasma renin activity (PRA), or aldosterone (Aldo). The present study was designed to determine whether the central nervous system (CNS) was the source of an unidentified substance, which could account for the blunting of the urine excretory response seen in the atrial-resected dogs. Renal denervation was performed in all dogs to eliminate alterations in efferent renal sympathetic nerve activity derived from reflexes activated during volume expansion. Cardiac denervation (CDX) was used to eliminate sensory cardiac afferent nerve activity to the CNS. A group of five renal-denervated dogs was given an isotonic volume load (400 ml/30 min) before and after complete CDX. Plasma AVP was fixed at normal plasma levels of 3 pg/ml by continuous intravenous infusion. Na and H2O excretion were not different in renal-denervated dogs compared with combined renal and cardiac denervation during the 5 h after the saline load. Plasma AVP and Aldo were unchanged with the volume loads, although PRA rose gradually over the 5 h after the saline loads. Plasma iANP increased transiently in the combined renal and cardiac-denervated state rising from a control of 65-120 pg/ml at the end of the load period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415603 TI - Factors involved in left ventricular dysfunction after massive sympathetic activation. AB - We sought to determine whether catecholamines are responsible for the depressed left ventricular (LV) function that follows massive sympathetic nervous system (SNS) activation and whether the additional myocardial energy demands of SNS induced hypertension contribute to this disorder. An intracisternal injection of veratrine was used to intensely activate the SNS of anesthetized rabbits, and 150 min later, LV function was evaluated in vitro using established techniques. To assess catecholamine involvement, rabbits were pretreated with phentolamine, propranolol, or saline prior to SNS activation. Control animals received veratrine intravenously. In separate experiments, angiotensin II (ANG II) was administered to rabbits to produce hemodynamic and plasma catecholamine profiles comparable to that produced by intense SNS activity. LV function of hearts after either massive SNS activation or ANG II administration was significantly diminished compared with control (P less than 0.01) and could be prevented by pretreatment with the catecholamine antagonists. LV function was also not diminished in another group of animals in which arterial pressure was maintained near baseline throughout the SNS discharge, thus suggesting that the increased myocardial energy demand associated with the development of arterial hypertension contributes to the LV dysfunction. We conclude that toxic concentrations of catecholamines are responsible for SNS-induced LV dysfunction and that hypertension, most likely because of its ability to increase myocardial energy demand, is one of the important events that leads to depressed cardiac function. PMID- 1415605 TI - Effects of aging on baroreflex regulation of sympathetic activity in humans. AB - Arterial baroreflexes contribute importantly to blood pressure regulation through their influence on parasympathetic outflow to the sinus node and sympathetic outflow to the peripheral circulation. Baroreflex control of heart rate is known to be diminished in older individuals. Whether advancing age is associated with a parallel attenuation in baroreflex control of sympathetic outflow to the peripheral circulation has not been studied in humans. To provide such information, we made direct measurements of muscle sympathetic nerve activity (MSNA) in healthy males who ranged in age from 18 to 71 yr. The subjects were arbitrarily divided into three groups: younger (18-34 yr; n = 35), middle aged (35-50 yr; n = 15), and older (51-71 yr; n = 16). Although basal levels of MSNA were higher in older subjects than in younger and middle-aged subjects, the gains of baroreflex control of MSNA were the same in the older, middle-aged, and younger subjects (-4.6 +/- 0.6, -4.8 +/- 0.9, -5.1 +/- 0.5 U/mmHg, P greater than 0.10). In contrast, the gains of baroreflex control of cardiac intervals were attenuated in the older and middle-aged subjects compared with the younger subjects (9.8 +/- 1.2, 13.6 +/- 1.4, 21.7 +/- 1.3 ms/mmHg, P less than 0.05). Our data indicate that although the parasympathetic component of the arterial baroreflex becomes impaired with advancing age, the sympathetic component can be well maintained in healthy individuals even into the seventh decade. PMID- 1415606 TI - Exercise training improves cardiac function after ischemia in the isolated, working rat heart. AB - The aim of this study was to determine whether exercise training produces a myocardium intrinsically more tolerant to ischemic-reperfusion injury. Male Fischer 344 rats were treadmill trained for 11-16 wk at one of the following intensities: LOW (20 m/min, 0% grade, 60 min/day), moderate (MOD; 30 m/min, 5% grade, 60 min/day) or intensive (INT; 10 bouts of alternating 2-min runs at 16 and 60 m/min, 5% grade). Cardiac function was evaluated both before and after 25 min of global, zero-flow ischemia in the isolated, working heart model. Compared to hearts from sedentary (SED) rats, postischemic cardiac output (CO) and work were significantly higher in all trained groups. Percent recovery of CO (relative to preischemia) was 36.0 +/- 7.1 in SED and 61.2 +/- 6.5, 68.1 +/- 9.3, and 73.2 +/- 5.0 in LOW, MOD, and INT, respectively. Postischemic increases in stroke volume with increased preload and cardiac work at high work load were significantly higher in INT compared with SED. Coronary flow during initial retrograde reperfusion was significantly enhanced with training and correlated with subsequent recovery of CO (R2 = 0.613). Furthermore, trained hearts had higher phosphocreatine (P less than 0.05) and ATP (P less than 0.01) contents after 45 min reperfusion. It is concluded that exercise training results in an intrinsic myocardial adaptation, allowing greater recovery of cardiac pump function after global ischemia in the isolated rat heart. PMID- 1415607 TI - Leukocyte adhesion in local versus hemorrhage-induced ischemia. AB - The objective of this study was to compare the leukocyte-endothelial cell adhesive interactions elicited in postcapillary venules by either local ischemia reperfusion or hemorrhage-reperfusion. Leukocyte rolling, adherence, and emigration were monitored in cat mesenteric venules exposed to an 85% reduction in blood flow (induced by either hemorrhage or local restriction of arterial inflow) for 1 h, followed by 1 h reperfusion. Leukocyte-endothelial cell interactions, venular diameter, and red blood cell velocity were measured during baseline, ischemia, and reperfusion periods. Both local and hemorrhage-induced ischemia reperfusion caused a reduction in leukocyte rolling velocity and increases in leukocyte adherence and emigration. Quantitatively, the adherence and emigration responses in both ischemia models were nearly identical. However, the two models differed in their response to immunoneutralization of the leukocyte adhesion glycoprotein CD11/CD18 with monoclonal antibody (MAb) IB4. The MAb had a more profound effect in attenuating leukocyte adherence and emigration in the local ischemia model. These results indicate that different factors may contribute to leukocyte-endothelial cell adhesive interactions observed in local vs. systemic models of ischemia-reperfusion. PMID- 1415608 TI - Effect of abrupt changes in ventricular loading on repolarization induced by transient aortic occlusion in humans. AB - We have investigated the influence of ventricular loading on repolarization from beat to beat in the human heart. Sixteen patients undergoing routine coronary artery surgery were studied. Left ventricular epicardial monophasic action potentials and local electrograms were recorded during acute changes in ventricular loading induced by transient aortic occlusion. Monophasic action potential duration shortened (P less than 0.0001) and returned to control values within one or two beats after release (P less than 0.0001). Values at 90% repolarization were 325 +/- 31 ms preocclusion, 311 +/- 29 ms during occlusion, 326 +/- 32 ms postocclusion. The Q-T interval of the local epicardial electrogram shortened during occlusion (P less than 0.001) and returned to control values after release (P greater than 0.0001): 396 +/- 44 ms preocclusion, 379 +/- 41 ms during occlusion, and, 399 +/- 42 ms postocclusion. A significant correlation was obtained between changes in peak systolic pressure and changes in monophasic action potential duration (R = 0.96; P less than 0.0001 at 90% repolarization). A significant correlation was also observed between changes in peak systolic pressure and the Q-T interval of the local electrogram (R = 0.91; P less than 0.0001). This study shows that abrupt changes in ventricular loading from one beat to the next induce significant changes in the timing of ventricular repolarization. These results may well be relevant to the initiation of arrhythmia by a single ventricular ectopic beat, particularly under pathological conditions. PMID- 1415609 TI - Thoracic aortic pressure-flow relationships and vascular impedance in fetal sheep. AB - Upper descending thoracic aortic pressures recorded from near-term fetal sheep resembled those recorded in mature animals, but diastolic thoracic aortic flows were much greater than those reported for adults. Furthermore, the pressure wave was not amplified during transmission along the aorta, as it is in adults. Descending thoracic impedance fell with increasing frequency to approximately 25% of resistance to steady flow and then showed oscillations typical of systems in which pulse wave reflections are important. Angiotensin II and norepinephrine infusions enhanced impedance oscillations and caused changes in apparent phase velocity in the aorta that were consistent with increased wave reflections. Angiotensin also increased aortic characteristic impedance from 0.0152 +/- 0.0013 to 0.0230 +/- 0.0024 mmHg.min.ml-1. The effects of nitroprusside infusions indicated reduced wave reflection effects. Embolization of the placenta and hindlimbs with 50-microns microspheres was used to elevate vascular resistance in these beds. Embolization caused aortic flow to fall to zero by late diastole, and changes in impedance and apparent phase velocity suggested increased wave reflections from the periphery. Characteristic impedance was increased to 0.0209 +/- 0.0031 mmHg.min.ml-1. PMID- 1415610 TI - Chronic captopril and losartan (DuP 753) administration in rats with high-output heart failure. AB - We investigated the role of atrial natriuretic factor (ANF) and the renin angiotensin system as well as the effects of losartan in rats with aortocaval (AC) shunts. Right atrial and left ventricular end-diastolic pressures (LVEDP) were higher and mean arterial blood pressure (MAP) was lower in AC shunt animals than in their controls. AC shunt rats presented marked cardiac hypertrophy, decreased right atrial ANF concentration, and increased ventricular ANF content and concentration. Plasma ANF levels were elevated, and hematocrit was lower in AC shunt animals than in controls. Captopril or losartan treatment decreased MAP and returned LVEDP to sham-operated control values. A clear regression of cardiac hypertrophy was evident in both treated AC shunt groups, with plasma ANF levels tending to follow those in sham-operated rats. Plasma COOH-terminal ANF levels were decreased and urinary volume and hematocrit were increased in losartan treated AC shunt animals. We conclude that chronic angiotensin converting enzyme inhibition and angiotension II receptor antagonism improved hemodynamic conditions, diminished water retention, reversed cardiac hypertrophy, and restored plasma and tissue ANF to more "normal" levels in rats with moderate high output heart failure. PMID- 1415611 TI - Mechanical performance of spared myocytes after myocardial infarction in rats: effects of captopril treatment. AB - To determine the effects of myocardial infarction-induced left ventricular failure on the mechanical characteristics of the remaining viable myocytes, coronary arterial occlusion was performed in rats, and cell function was examined 1 wk later. Moreover, to establish the mechanisms by which treatment with angiotensin-converting enzyme inhibitors ameliorates cardiac dynamics, captopril was administered immediately after surgery, and the contractile behavior of the unaffected cells was similarly analyzed 7 days later. The severe impairment in left-side pump function was found to be associated with a decrease in the velocities of myocyte shortening and relengthening and peak shortening despite a prolongation of contraction duration. In addition, a uniform property was recognized in myocytes from infarcted and noninfarcted hearts. Longer cells manifested greater velocity of shortening, whereas wider cells of identical length exhibited depressed shortening velocity. After infarction, the depression in cell contractility coupled with lateral expansion of myocytes exceeded the influence on cell mechanical behavior linked to myocyte lengthening leading to an overall decrease in contractility of the hypertrophied cells. Captopril therapy preserved, in part, the ability of myocytes to shorten and relengthen, which was accompanied by a decrease in the lateral and longitudinal expansions of these cells. PMID- 1415612 TI - Cardiac venous endothelial dysfunction after myocardial ischemia and reperfusion in dogs. AB - Endothelial dysfunction is a prominent occurrence in coronary arteries after myocardial ischemia and reperfusion. However, this has not been studied in coronary veins. Endothelium-dependent vasorelaxation was studied in cardiac venous rings obtained from dogs subjected to 60 min of coronary artery occlusion followed by 270 min of reperfusion, as well as from dogs subjected to sham ischemia-reperfusion. Myocardial ischemia resulted in a 96 +/- 2% decrease in coronary flow to the ischemic area 60 min after occlusion of the left anterior descending (LAD) coronary artery, which led to a significant degree of cardiac necrosis (i.e., 32.9 +/- 3.9% of area at risk). Cardiac venous rings isolated from sham ischemia-reperfusion dogs relaxed 68 +/- 3% to 200 microM ADP, 65 +/- 3% to 2 microM A23187, and 76 +/- 4% to 200 microM sodium nitrite (NaNO2). Corresponding values for cardiac venous rings isolated from ischemic-reperfused dogs were 32 +/- 3% for 200 microM ADP (P less than 0.01 vs. sham), 31 +/- 3% for 2 microM A23187 (P less than 0.01 vs. sham), and 74 +/- 3% for 200 microM NaNO2 (NS from sham). In rings from control dogs, vasorelaxation to ADP and A23187 was markedly inhibited by 4 mM NG-methyl-L-arginine (L-NMMA) and 10 methylene blue and restored after NG-nitro-L-arginine by 3 mM L-arginine. These results demonstrate that a significant degree of endothelial dysfunction occurred in cardiac venous rings after ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415613 TI - Na+ efflux mechanisms in ventricular myocytes: measurement of [Na+]i with Na(+) binding benzofuran isophthalate. AB - We characterized the Na(+)-sensitive dye benzofuran isophthalate (SBFI) with fluorescence microscopy in isolated, adult rat ventricular myocytes. When cells were loaded with SBFI by incubation with 10 microM of the acetoxymethyl ester, fluorescence excitation spectra were markedly attenuated below 340 nm and the isoemissive point was blue shifted by approximately 25 nm when compared with spectra from SBFI acid in buffered solutions. Fluorescence intensity (49 +/- 3%) was partially released by permeabilization of the sarcolemma with digitonin, suggesting that one-half of the dye molecules are sequestered subcellularly in a compartment shown most likely to be mitochondrial. Intracellular Na+ concentration ([Na+]i) was determined by in situ calibration using cation selective ionophores and was found to be 14 +/- 2 mM in cells studied at 37 degrees C. The relative importance of Na+ efflux mechanisms in myocytes was investigated. Substitution of Ca2+ and Mg2+ with EGTA in the superfusing medium resulted in a reversible rise of [Na+]i from 13 +/- 2 to 31 +/- 5 mM, which was blocked by 1 microM verapamil. Cellular efflux of Na+ after loading in this manner was found to be insensitive to blockade of Na(+)-Ca2+ exchange but was abolished when Na(+)-K(+)-ATPase was inhibited with zero extracellular K+ concentration. We conclude that SBFI can be used to measure [Na+]i in ventricular cells nondestructively and without impalement. Na+ efflux after loading by Ca2+ and Mg2+ withdrawal is mediated by the Na+ pump with no measurable contribution from Na(+)-Ca2+ exchange. PMID- 1415614 TI - Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation. AB - To determine the hemodynamic effects of exogenous nitric oxide (NO) on the immature pulmonary circulation, we studied the response to NO inhalation in 19 mechanically ventilated late-gestation ovine fetuses in three separate protocols. In protocol 1, we examined the relative effects of 1) mechanical ventilation while maintaining fetal arterial O2 tension (PaO2) constant [fractional inspired O2 concentration (FIO2) less than 0.10)], 2) NO inhalation [5-20 parts per million (ppm)] at fetal PaO2, and 3) high FIO2 (1.00) (n = 7). NO increased left pulmonary artery blood flow (Qlpa) in a dose-dependent fashion, from 254 +/- 62 (baseline) to 398 +/- 49 ml/min with 20 ppm NO (P less than 0.001). The response of Qlpa to a FIO2 equal to 1.00 was not different from NO alone. Systemic arterial pressure was not affected by NO. In protocol 2 we studied the effects of prolonged NO inhalation (2 h, 20 ppm) during mechanical ventilation with low FIO2 (n = 4). NO increased Qlpa from 267 +/- 92 to 468 +/- 75 ml/min at 10 min of NO inhalation (P less than 0.001). The increase in Qlpa was sustained during the entire 2-h study period. In protocol 3 we measured left ventricular output (LVO), systemic vascular resistance (SVR), and ductus arteriosus shunting using radiolabeled microspheres (n = 8) during baseline mechanical ventilation and 20 ppm NO inhalation. LVO and SVR were not significantly different in the two study periods; however, the percentage of LVO that reached the lungs (predominantly left-to-right shunting across the ductus arteriosus) increased from 18 +/- 5 to 43 +/- 4% during NO inhalation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415615 TI - Pulmonary and systemic vascular smooth muscle mechanical characteristics in newborn sheep. AB - To investigate the hypothesis that the higher pulmonary vascular resistance in newborn sheep is the result of developmental differences in the vascular muscle mechanical properties, we evaluated pulmonary arteries from newborn and adult sheep and compared them with their respective systemic counterparts (common carotid arteries). The newborn pulmonary artery mechanical stress (13.0 +/- 1.4 mN/mm2) and shortening capacity (11.4 +/- 1.1% of optimal length) were lower (P less than 0.01) than in the adult (20.4 +/- 2.5 and 15.6 +/- 1.3, respectively). The adult carotid artery muscle developed a greater stress (97.6 +/- 18.5 mN/mm2) than the newborn (40.7 +/- 5.0; P less than 0.01), whereas no age differences in shortening capacity were observed (newborn = 19.4 +/- 1.7; adult = 18.4 +/- 1.5% of optimal length). The contraction half-time was similar for the pulmonary and carotid arteries and was not affected by age, whereas the relaxation half-times of the newborn pulmonary (30.7 +/- 2.9 s) and carotid artery (23.3 +/- 1.5) were greater than in the adult (24.9 +/- 2.9 and 14.6 +/- 1.4, respectively; P less than 0.01). The myosin contents of the pulmonary and carotid arteries, as an indicator of the tissue muscle mass, were similar and did not change with age. In conclusion, while the lower stress and shortening capacity of the newborn pulmonary arteries limit their maximum capacity to vasoconstrict, the significantly greater relaxation time of their vascular muscle, a new observation, may account for the higher resistance to blood flow after birth. PMID- 1415616 TI - Ischemic preconditioning attenuates acidosis and postischemic dysfunction in isolated rat heart. AB - The hypothesis that brief ischemia (preconditioning) protects the isolated heart from prolonged global ischemia was tested. Isovolumic rat hearts were preconditioned with either 5 min of ischemia followed by 5 min of perfusion (P1) or two 5-min episodes of ischemia separated by 5 min of perfusion (P2). Control hearts received no preconditioning. All hearts received 40 min of sustained ischemia and 30 min of reperfusion. Preconditioning (P1 or P2) significantly (P less than 0.0005) improved recovery of the rate-pressure product; percentage recoveries were 17.8 +/- 3.2 (n = 14), 59.9 +/- 5.5 (n = 6), and 46.4 +/- 4.7 (n = 8) for control, P1, and P2, respectively. Improved functional recovery of preconditioned hearts was associated with reduced end-diastolic pressure and improved myocardial perfusion. During the 40-min ischemic period, myocardial pH decreased from approximately 7.4 to 6.3 +/- 0.1 (n = 7) in the control hearts and to 6.7 +/- 0.1 (n = 7) in the preconditioned hearts (P less than 0.01). Also during the 40-min ischemic period, myocardial lactate (expressed as nmol/mg protein) increased to 146 +/- 11 (n = 7) and 101 +/- 12 (n = 8) in control and preconditioned hearts, respectively (P less than 0.02). The results demonstrate that a brief episode of ischemia can protect the isolated rat heart from a prolonged period of ischemia. This protection is associated with decreased tissue acidosis and anaerobic glycolysis during the sustained ischemic period. PMID- 1415617 TI - Comparison of protein lymph flux and extravascular uptake in skin during increased venous pressure. AB - The hypothesis that the albumin reflection coefficient is underestimated from measurements of lymph protein flux because of a prolonged interstitial washout was tested in the hindleg of anesthetized rabbits. In heel skin, the initial extravascular uptake for labeled albumin and immunoglobulin G (IgG) was compared with prenodal lymph flux for native albumin and IgG. Venous pressure was increased in one leg for 4 h, while the contralateral leg was the control. The extravascular uptake for labeled albumin was 67% greater than control during the fourth hour of increased venous pressure. Lymph albumin flux was 2.3 times control, indicating a small but significant washout of interstitial albumin. The magnitude of the interstitial washout for IgG was less than that for albumin. Using the relationship between the change in extravascular uptake and the change in lymph flow, the reflection coefficients for albumin and IgG were both 0.91. The reflection coefficient for albumin using lymph protein flux was lower because of a continued interstitial washout. PMID- 1415618 TI - 31P-NMR of high-energy phosphates in perfused rat heart during metabolic acidosis. AB - Intracellular pH (pHi), intracellular free magnesium concentration ([Mg2+]i), and high-energy phosphates in Langendorff perfused rat hearts were evaluated by 31P nuclear magnetic resonance (NMR) during metabolic acidosis. During acidosis, cardiac pHi approached that of the perfusing solution (pH approximately 6.7) and [Mg2+]i increased. In hearts perfused with glucose as the sole carbon source, the ratio of [phosphocreatine] to [ATP] decreased during acidosis. In contrast, in hearts supplemented with pyruvate (either 2.8 or 10 mM) this ratio increased during acidosis. Oxygen consumption decreased in hearts perfused with glucose only and with pyruvate-glucose. Using the creatine kinase equilibrium constant, we find that [MgADP] is significantly decreased in pyruvate-perfused hearts but is not significantly altered in glucose-perfused hearts during metabolic acidosis. These data indicate that [MgADP] may be the regulator of cardiac oxidative phosphorylation in the presence of excess pyruvate; however, during metabolic acidosis in hearts perfused with glucose only, ATP synthesis appears limited by the availability of pyruvate via glycolysis. PMID- 1415619 TI - Fetal cardiac bypass alters regional blood flows, arterial blood gases, and hemodynamics in sheep. AB - Successful fetal cardiac bypass might allow prenatal correction of some congenital heart defects. However, previous studies have shown that fetal cardiac bypass may result in impaired fetal gas exchange after bypass. To investigate the etiology of this impairment, we determined whether fetal cardiac bypass causes a redistribution of fetal regional blood flows and, if so, whether a vasodilator (sodium nitroprusside) can prevent this redistribution. We also determined the effects of fetal cardiac bypass with and without nitroprusside on fetal arterial blood gases and hemodynamics. Eighteen fetal sheep were studied in utero under general anesthesia. Seven fetuses underwent bypass without nitroprusside, six underwent bypass with nitroprusside, and five were no-bypass controls. Blood flows were determined using radionuclide-labeled microspheres. After bypass without nitroprusside, placental blood flow decreased by 25-60%, whereas cardiac output increased by 15-25%. Flow to all other fetal organs increased or remained unchanged. Decreased placental blood flow after bypass was accompanied by a fall in PO2 and a rise in PCO2. Nitroprusside improved placental blood flow, cardiac output, and arterial blood gases after bypass. Thus fetal cardiac bypass causes a redistribution of regional blood flow away from the placenta and toward the other fetal organs. Nitroprusside partially prevents this redistribution. Methods of improving placental blood flow in the postbypass period may prove critical to the success of fetal cardiac bypass. PMID- 1415620 TI - Low-dose endothelin-1 potentiates volume-induced secretion of atrial natriuretic factor. AB - To evaluate the role of calcium in volume-induced secretion of atrial natriuretic factor (ANF), effects of verapamil and endothelin-1 (ET-1), both known to influence free intracellular calcium, were studied during saline infusion in seven conscious instrumented dogs. Fifteen minutes after intravenous injection of placebo or verapamil (0.25 mg/kg) or during continuous ET-1 infusion (at 5 ng.kg 1.min-1), saline (10% body wt) was infused during 40 min. Saline produced a rise (P less than 0.001) of plasma ANF from 28.1 +/- 6.3 to 50.4 +/- 12.9 pM after placebo, from 30.2 +/- 6.1 to 51.1 +/- 8.5 pM after verapamil, and from 31.2 +/- 6.1 to 81.0 +/- 12.9 pM with ET-1. This increase was comparable after placebo and verapamil, but was 80% greater with ET-1 (P less than 0.02). Plasma ET-1, unchanged after placebo, rose (P less than 0.001) from 1.7 +/- 0.5 to 38.3 +/- 9.2 pM with ET-1. In the three experiments, heart rate and left atrial pressure (LAP) increased (P less than 0.001) similarly. The linear relation between ANF and LAP was steeper with ET-1 than with saline or verapamil (both P less than 0.05), indicating that the enhanced ANF secretion with ET-1 was occurring at all levels of LAP. Thus volume-induced secretion of ANF is not suppressed by verapamil, but is directly enhanced by low-dose ET-1, known to activate the phosphoinositide pathway. PMID- 1415621 TI - Concurrent increases in regional hematocrit and blood flow in diabetic rats: prevention by sorbinil. AB - These studies were undertaken to investigate the relationship between regional hemodynamic and hemorheological changes in the microvasculature of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injection of streptozotocin (55 mg/kg body wt). Control rats were injected with vehicle (sodium citrate buffer). A subgroup of diabetic rats was treated with an aldose reductase inhibitor (sorbinil) added to the diet in an amount to provide a daily dose of approximately 0.2 mmol.kg-1.day-1. Three weeks later all animals were anesthetized with thiobutabarbital sodium (Inactin, 100 mg/kg injected intraperitoneally) for assessment of blood flow (by injection of 15 microns microspheres) and regional hematocrit (determined by isotope-dilution techniques using 51Cr-labeled red blood cells and 125I-labeled bovine serum albumin) in selected tissues. The hematocrit in arterial blood samples was identical (approximately 46%) in controls and in diabetics. Regional hematocrits were much lower than arterial hematocrits in control rats and ranged from approximately 20% in ocular tissues, sciatic nerve, diaphragm, and skin to approximately 30% in brain, skeletal muscle, heart, and fat. Hematocrits of diabetic rats were markedly increased in ocular tissues, sciatic nerve, and skin but not in brain, heart, or skeletal muscle. These increases in regional hematocrit were associated with increases in blood flow and were largely prevented by sorbinil. Diabetes induced significant decreases in the mean transit times for whole blood and erythrocytes in all tissues examined except brain, retina, and skin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415622 TI - Endothelin in thoracic inferior vena caval constriction model of heart failure. AB - Recent studies have found endothelin-1 (ET), a potent vasoconstrictor of endothelial cell origin, is increased in congestive heart failure (CHF) in plasma and correlates with increased atrial pressures. Additionally, it has been shown that, despite increased circulating ET concentrations in CHF, a decreased responsiveness to exogenous ET infusion exists in an experimental model of CHF induced by rapid pacing. The present study was designed to determine whether plasma ET would be increased in a model of low cardiac output congestive failure without elevated atrial pressures produced by thoracic inferior vena caval constriction (TIVCC). In addition, we sought to determine whether this model of low cardiac output would show a full vasoconstrictive response to exogenous ET infusion and whether atrial natriuretic factor (ANF) infused acutely to achieve pathophysiological concentrations would modulate the systemic and renal hemodynamic responses to exogenous ET. Dogs were studied in the anesthetized state at 8-9 days after the TIVCC or sham operation. Baseline ET levels were significantly increased in the TIVCC dogs (n = 14) compared with sham operated dogs (n = 6; 41.4 +/- 7.1 vs. 17.9 +/- 1.5 pg/ml, respectively; P less than 0.05). With exogenous ET infusion (5 ng.kg-1.min-1), an intact systemic and renal vasoconstrictor response in the TIVCC dogs was observed. ANF prevented the systemic vascular and arterial pressure responses to ET. However, the potent renal vasoconstricting action of ET was not prevented by ANF. These studies suggest that ET may play an important role in maintaining blood pressure in the setting of low cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415623 TI - Hypoxia induces endothelial cells to increase their adherence for neutrophils: role of PAF. AB - We investigated the interactions of polymorphonuclear neutrophils (PMN) and endothelial cells in myocardial ischemia using a hypoxia model. We exposed porcine aortic (PAEC) and porcine coronary microvessel (PCMEC) endothelial cells to 2% O2 for 2 h (PO2 = 53 mmHg) and measured the adherence of unstimulated neutrophils (PMN) to both control and hypoxia-conditioned endothelial cell monolayers. Hypoxia conditioning increased PMN adherence to PAEC and PCMEC by 51 and 101%, respectively, above control levels. The increase in PMN adhesion to PAEC was associated with a threefold increase in endothelial cell-associated platelet-activating factor (PAF) compared with control PAEC. The conditioned media from PAEC exposed to hypoxia also contained sixfold more PAF than control conditioned media, and it activated PMN to become adherent to untreated PAEC. The hypoxia-induced PAEC adhesion response was inhibited by preincubating PMN with the specific PAF receptor antagonist, L-659,989. We conclude that PAF is produced by cultured endothelial cells in response to hypoxia and that PAF generation is chiefly responsible for the increased adherence properties of hypoxia-conditioned endothelial cells. This response may play a major role in regulating PMN margination during myocardial ischemia. PMID- 1415624 TI - Dynamic intramyocardial blood volume: evaluation with a radiological opaque marker method. AB - In this study the change of intramyocardial blood volume within one cardiac cycle was deduced from the time sequence of the volume delineated by radiopaque markers attached to the left ventricular wall. These data were compared with the change in the volume of the same region of myocardium estimated from the change in angiographic opacification of the heart wall. Five dogs were anesthetized, and four pairs of 2-mm-diameter lead beads were attached to the epicardial and endocardial regions. Two scans using the dynamic spatial reconstructor (a high speed computed tomographic scanner) were performed during aortograms, one under control conditions and the other during adenosine infusion. The results have shown that the increases of myocardial volume defined by the beads (delta Vbead, % of volume at control) were comparable to the increase of intramyocardial blood volumes estimated by the increase in wall opacity (delta Vblood, % of muscle); delta Vblood = 0.93 delta Vbead + 1.54%; r = 0.987. PMID- 1415625 TI - Measurement of biventricular septal-to-free wall diameters using sonomicrocrystals. AB - An ultrasonic system for the measurement of biventricular septal-to-free wall internal diameters in the dog was described. The ventricular endocardial ultrasonic microcrystals were implanted via the left and right atrial appendages and arranged in a straight line, with minimal invasion of the myocardium and pericardium. Reliable signals were obtained during right ventricular pressure overload and septal myocardial ischemia. PMID- 1415626 TI - Suppression of motion artifacts in fluorescence spectroscopy of perfused hearts. AB - Fluorescence spectroscopy of beating hearts has been used previously to measure intracellular regulators of function. Unfortunately, heart motion could introduce a spurious motion artifact (MA), influencing the measured fluorescence intensity ("signal"). To suppress MA, a ratio (or difference) has been calculated previously between the signal and an intensity reference detected at a different wavelength ("reference"). However, no studies have attempted to evaluate or optimize the efficiency of MA suppression. MA suppression was evaluated using reflected excitation light or fluorescence as reference. In addition, the MA contribution to the intensity ratio from a fluorescent dye, indo-1, was quantified. A reflected light reference resulted in poor suppression of MA. The use of a fluorescence reference resulted in suppression that was inversely related to the detection wavelength difference (delta) between the reference and signal. Therefore optimal MA suppression was obtained using a fluorescence reference at a wavelength close to the signal. For delta = 60 nm, MA was suppressed from approximately 10 to less than 2%. Finally, suppressed MA (delta = 60 nm) accounted for less than 10% of the indo-1 ratio fluctuations. PMID- 1415627 TI - Use and limitations of thiobarbituric acid reaction to detect lipid peroxidation. PMID- 1415628 TI - Vertebrate intestine apical membrane mechanisms of organic nutrient transport. AB - This paper presents the current understanding of comparative vertebrate intestine basic mechanisms of brush-border membrane transport. Animals control the uptake of monosaccharides and amino acids at three levels: 1) mucosal hyperplasia increases uptake nonselectively, 2) individual enterocytes increase the transport capacity of specific transporter systems, and 3) the transporters themselves are modulated by solute and ion electrochemical gradients. In light of the current literature, This paper summarizes the kinetics, thermodynamics, and the physical arrangement of one mode of transport, the prototype Na(+)-solute cotransporter. The model presented is experimentally consistent with "preferred random" kinetics, with Na+ binding preferentially before solute at the extracellular face. In the case of glucose, the cotransporter system may be physically arranged in the membrane as a tetramer comprising 73,000 Da subunits. All vertebrates may have evolved with a similar mechanism, with particular variations reflecting selected arrangements from a pool of polypeptide sequence blocks. The same fundamental transport mechanisms may be observed in the intestines of animals ranging from lower vertebrates through humans. PMID- 1415630 TI - Invertebrate gut diverticula are nutrient absorptive organs. AB - Physiological mechanisms of gastrointestinal absorption and secretion of organic and inorganic solutes among invertebrates remain severely underinvestigated. In this review we briefly discuss some of the physical and biological forces affecting solute transfer across epithelial cells and membranes of vertebrate and invertebrate guts. Next, we present some features of the described processes for sugar and amino acid transport in the tubular portion of gastrointestinal tracts of three major invertebrate groups: echinoderms, molluscs, and arthropods. A detailed discussion follows of recent nutrient transport studies using purified epithelial brush-border membrane vesicles of two invertebrate gut diverticula, the crustacean hepatopancreas and the starfish pyloric cecum. Lastly, transepithelial nutrient and ion transport studies of crustacean hepatopancreatic epithelial cell monolayers, grown in primary culture and mounted in flux chambers, are used to demonstrate the nature of absorption and secretion of solutes by this organ and to show the general applicability of these methods to structurally complex invertebrate organs. PMID- 1415631 TI - Role of intestinal basolateral membrane in absorption of nutrients. AB - Organic solutes leave the intestinal epithelium and enter the circulation via specific facilitated carriers located in the basolateral membrane. In the case of glucose it is a low-affinity, high-capacity transport system that can adapt to the carbohydrate content of the diet. Chronic diabetes also promotes the exit of glucose, and in both cases the effect results from an increased density of carriers in the basolateral membrane. In contrast, a rapid upregulation of this system that can be induced within 30 min by hyperglycemia does not involve large changes in the amount of transporter protein. Similarly, the absorptive capacity of the small intestine from some amino acids can be influenced by events occurring at the basolateral membrane. In the case of dibasic amino acid absorption, exit from the epithelium is the rate-limiting step. The activity of the basolateral carrier can be increased almost 10-fold within 60 s by the addition of micromolar concentrations of the neutral amino acid leucine to either the lumen or the plasma. This response does not involve the second messenger adenosine 3',5'-cyclic monophosphate and may represent an allosteric modulation of the carrier. These observations are discussed in relation to the role of the basolateral membrane as a locus for controlling intestinal absorption of organic nutrients. PMID- 1415629 TI - Comparative aspects of lipid digestion and absorption: physiological correlates of wax ester digestion. AB - Our understanding of lipid digestion and absorption is largely derived from studies with glyceride-based dietary lipids. Yet for a great majority of marine species, wax esters (long-chain fatty alcohols esterified to long-chain fatty acids) are the dominant dietary neutral lipid. Many birds, especially seabirds (9 species) and some passerines (2 species), have a unique capacity for assimilating wax esters with higher efficiencies (greater than 90%) than that attainable by mammals (less than 50%). This unique capacity is correlated with several factors. One factor is an elevated intestinal bile salt concentration approaching 50 mM and a gallbladder concentration exceeding 600 mM. A second factor involves regular retrograde movement of duodenal contents to the gizzard. Thus not only is gastric emptying closely tied to the receptiveness of the duodenum for further handling of digesta as in mammals, but in birds the reflux returns the digesta (both gastric and duodenal) for further processing to the gizzard. A third key factor in wax ester utilization is a nearly equivalent hydrolysis of wax esters and triglycerides. Although similarities in fat digestion exist between birds and mammals, there do exist differences that make nonpolar lipid assimilation (i.e., wax esters) more efficient in birds, especially for seabirds. PMID- 1415632 TI - Molecular biology approaches to comparative study of Na(+)-glucose cotransport. AB - The rabbit intestinal Na(+)-glucose cotransporter has been cloned and sequenced. The cDNA encoding the cotransporter has been used in two general lines of research related to comparative aspects of Na(+)-glucose cotransport that are reviewed here. First, defined regions of the predicted amino acid sequence were used to raise antibodies, and the species distribution of epitopes recognized by those antibodies was investigated. Intestinal brush-border membranes from mammals, birds, an amphibian, and a reptile were all found to contain protein that were recognized by the antibodies in Western analysis. The cDNA encoding the rabbit intestinal Na(+)-glucose cotransporter was also used directly to examine the species distribution of related mRNA in Northern studies and to isolate new cDNAs encoding other Na(+)-glucose cotransporters. Northern blots revealed the presence of related mRNAs in intestines of mammals and a fish, as well as rabbit kidney and gills of marine mussels. The cDNAs encoding mammalian Na(+)-glucose cotransporters and bacterial Na(+)-dependent cotransporters for proline and pantothenate share sequence homology. There has been evolutionary conservation of the structure and function of the Na(+)-glucose cotransporter, and there appears to be a gene family that codes for the Na(+)-coupled cotransporters. PMID- 1415633 TI - Tests of the adaptive modulation hypothesis for dietary control of intestinal nutrient transport. AB - According to the adaptive modulation hypothesis, an intestinal transporter should be repressed when its biosynthetic and other costs (of maintenance) exceed the benefits it provides. This leads to two contrasting predictions: transport of a sugar or amino acid worth calories should tend to be increased by its substrate, and transport of a vitamin should be modulated downwards by its substrate and upmodulated in deficiency. In a test of the first prediction, omnivorous desert iguanas eating alfalfa pellets (a high-carbohydrate diet) were compared with desert iguanas eating mealworms (a low-carbohydrate, higher-protein diet). In accord with the prediction, intact intestinal sleeves from the former group had higher rates of carrier-mediated D-glucose uptake/centimeter across the brush border than sleeves from the latter group. But in contrast to the first prediction, mealworm eaters had lower (not higher) proline uptake rates, and the ratio of glucose/proline uptake in the two groups did not differ. I review similar tests in 12 other species and show that overall the hypothesis has been quite robust with regard to the first prediction. Cases in which the hypothesis is rejected may reflect complications associated with changes in other dietary factors or phylogenetic constraints. In a test of the second prediction, uptake of the water-soluble vitamin choline was not increased in choline-deficient chicks, nor was it decreased in adults that have no dietary requirement for choline. I review similar tests for four other vitamins and five essential minerals. Dietary control of transport of the minerals and two of the vitamins seems to be in accord with the hypothesis. But transport rate for three vitamins (choline, pantothenic acid, ascorbic acid) seems not to be increased in deficiency. The best explanation seems to be that vitamin transport is modulated only if it is primarily by a carrier-mediated pathway. PMID- 1415634 TI - Intestinal nutrient transport during ontogeny of vertebrates. AB - Patterns of transporter development are known for 12 species of vertebrates (2 fish, 1 amphibian, 1 bird, and 8 mammals), ranging from early gestation to adulthood. Although transporters for some nutrients (amino acids and some sugars) appear before the onset of external feeding, species differ in when and which transporters appear. Postnatal changes in the activities of different transporters are twofold: corresponding with shifts in the composition of a species' evolutionary diet, and the need to absorb ever-increasing quantities of food for growth and metabolism. The mechanisms responsible for the age-related shifts in rates of transport include changes in the densities, distribution, and types of transporters for specific nutrients and changes in the physiochemical characteristics of the intestinal brush-border membrane. The signals that trigger the age-related changes originate from internal preprogrammed sources and external sources, with both acting in concert to mediate intestinal development. Although much more is known for the brush-border hydrolases, recent studies with the pig suggest the ontogenetic development of hydrolases and transporters are regulated independently during early development. PMID- 1415635 TI - Role of endothelium-derived nitric oxide in the renal hemodynamic response to amino acid infusion. AB - The present study was performed in anesthetized rats to compare the renal hemodynamic responses to mixed amino acids (M-AA) with those to L-arginine (L Arg) and to examine the effect of endothelium-derived nitric oxide (EDNO) synthesis blockade on the M-AA-induced rise in renal plasma flow (RPF) and glomerular filtration rate (GFR). Intravenous infusion of both M-AA (Ser, Gly, Ala, and Pro, 0.71 mmol.100 g-1.min-1) and L-Arg (0.71 mmol.100 g-1.min-1) increased RPF and GFR. Peak increases in RPF for M-AA and L-Arg were 39.7% (P less than 0.05) and 63.4% (P less than 0.01), whereas GFR increases were 33.6% (P less than 0.05) and 46.7% (P less than 0.01, respectively). Outer cortical blood flow (OCBF) was increased with both treatments. Sodium excretion and urine flow were increased more with L-Arg than M-AA (both P less than 0.01). Infusion of the nitric oxide synthesis inhibitor, nitro-L-arginine (N-L-Arg, 20 micrograms.100 g 1.min-1) increased mean arterial pressure but decreased RPF 48.4% (P less than 0.001), OCBF 39.5% (P less than 0.001), GFR 37.8% (P less than 0.01), urine flow 29.8% (P less than 0.01), and sodium excretion 40.9% (P less than 0.01). When M AA was administered after N-L-Arg, significant increases in OCBF, RPF, and GFR were observed (P less than 0.01); there was also an enhancement of sodium excretion and urine flow (both P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415636 TI - Maintenance of intestinal nutrient transport during hibernation. AB - We studied nutrient absorption across the brush-border membrane in jejunal tissues from active 13-lined ground squirrels and in hibernating squirrels that had not eaten for at least 6 wk. Body weights and jejunal wet weights per centimeter were significantly reduced in the hibernators. Rates of total and carrier-mediated uptake of 3-O-methylglucose (3-OMG) per centimeter intestinal length were greater in the active squirrels, but 3-OMG uptakes per milligram intestinal weight were greater in the hibernators, due to a significantly greater maximum rate of uptake (Jmax) per milligram with no differences in apparent Michaelis constant (Km). Passive permeabilities to L-glucose were similar in both groups. Total uptake of L-proline per centimeter was greater in active squirrels, but total proline uptake per milligram was greater in the hibernators due to a significantly greater Jmax per milligram with no difference in apparent Km. Na(+) independent proline uptake accounted for a greater proportion of total proline uptake in active compared with hibernating squirrels. As a consequence, Na(+) dependent proline uptake was greater in the hibernators when uptake was normalized either to intestinal length or intestinal weight. Thus hibernation is associated with an increase in the Jmax per milligram for 3-OMG and proline transport, as well as a shift in the Na+ dependency of proline uptake. We conclude that nutrient absorption is selectively retained in mammalian hibernators to maintain transport function after the extended winter fast. PMID- 1415637 TI - Arterial baroreflex dynamics in normotensive and spontaneously hypertensive rats. AB - To investigate dynamic or frequency-dependent characteristics of arterial baroreflex control of efferent sympathetic nerve activity in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), we assessed the transfer function from aortic pressure (AP) to renal sympathetic nerve activity (RSNA) using a "white-noise technique." In pentobarbital sodium-anesthetized rats, we recorded RSNA as the output, while AP was randomly perturbed to impose input pressure changes with broad frequencies. We calculated the transfer function from AP to RSNA over the frequency range of 0.01-5 Hz through the spectral analysis of the input and output. The results indicated that the gain, phase shift, and coherence of the transfer function for SHR and for WKY were similar and statistically indistinguishable. The gain was relatively constant below 0.05 Hz but increased steadily by fivefold as frequency increased in the frequency range of 0.05-0.8 Hz. The phase was out of phase where coherence was high. The coherence was high (greater than 0.5) in the frequency range of 0.04-0.8 and 1.00 1.03 Hz but was low in other frequencies. These results suggest that dynamic or frequency-dependent characteristics of arterial baroreflex control of RSNA were not altered in SHR as compared with WKY. PMID- 1415638 TI - Physiological concentrations of ANP exert a dual regulatory influence on renin release in conscious dogs. AB - The influence of physiological increments in circulating atrial natriuretic peptide (ANP) on renin release was determined in conscious dogs. Renin stimulus response curves (RSRCs) were obtained by controlled reductions of renal perfusion pressure (RPP) under control conditions and during intrarenal or intravenous ANP infusions. Under all experimental conditions, the RSRCs were characterized by a plateau, a threshold pressure (Pth), and a steep slope below Pth. Intrarenal ANP infusion (0.9 ng.kg-1.min-1), which induced a calculated threefold elevation of renal arterial ANP concentration (but did not change systemic arterial ANP levels), increased the slope of the RSRC by 81% (P less than 0.05) with no effect on Pth. A quantitatively similar effect on the slope of the RSRC (+90%; P less than 0.05) was observed when systemic ANP levels were raised (from 37 +/- 2 to 71 +/- 9 pg/ml; P less than 0.05) by intravenous infusions (3.6 ng.kg-1.min-1). In addition, however, intravenously infused ANP reduced Pth from 91 to 85 mmHg (P less than 0.05), which caused a complete suppression of the renin response to a reduction of RPP down to 85 mmHg. These findings indicate that ANP can inhibit renin release at physiological plasma concentrations by shifting the RSRC to a lower pressure level; this shift is mediated by a modulation of extrarenal renin control mechanisms. The direct effect of ANP on renin release is one of stimulation. PMID- 1415639 TI - Interactions of physiological and pharmacological concentrations of ANP and angiotensin II in conscious dogs. AB - This study in conscious, chronically instrumented dogs investigated the effects of human atrial natriuretic peptide [hANP-(99-126)] at physiological (5 ng.kg 1.min-1) and pharmacological (5-900 ng.kg-1.min-1) doses on angiotensin II (ANG II)-mediated effects on hemodynamics, renal excretion, and aldosterone release. Five female beagle dogs kept chronically on a dietary sodium intake of 2.5 mmol Na.kg body wt-1.day-1 received an intravenous infusion of 1, 4, 10, 20, and 50 ng.kg-1.min-1 ANG II (20-min periods) without (protocol 1) or with (protocol 2) simultaneous intravenous infusion of 5 ng.kg-1.min-1 hANP-(99-126). In protocol 1, glomerular filtration rate (means +/- SD) decreased from 4.0 +/- 0.6 to 2.8 +/ 0.5 ml.kg-1.min-1, renal sodium excretion (UNaV) decreased from 2.8 +/- 1.6 to 0.4 +/- 0.2 mumol.kg-1.min-1, and urine volume (V) decreased from 45 +/- 23 to 6 +/- 8 microliters.kg-1.min-1. There were no differences in the values between protocol 1 and protocol 2. Mean arterial blood pressure (MABP) increased similarly from 118 +/- 16 to 166 +/- 9 mmHg in protocol 1 and from 109 +/- 11 to 162 +/- 7 mmHg in protocol 2. Maximal aldosterone secretion was stimulated less in protocol 2 (481 +/- 92 vs. 362 +/- 158 pg/ml; P less than 0.05). In ANG II pretreated (20 ng.kg-1.min-1) dogs (n = 4; protocol 3), intravenous hANP-(99-126) doses of 300-900 ng.kg-1.min-1 decreased MABP and central venous pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415640 TI - Hypothalamic and cortical sympathetic responses relay in the medulla of the rat. AB - Previously, investigations have indicated that the efferent pathway for sympathetic responses originating in the insular cortex (IC) must initially synapse in the lateral hypothalamic area (LHA). The LHA projects to both the ventrolateral medulla (VLM) and directly to the thoracic spinal cord. To determine the role of the VLM in mediating sympathetic responses from the IC and the LHA, in alpha-chloralose-anesthetized rats, renal nerve responses were recorded following electrical stimulation of these two forebrain sites before and after bilateral injection (300 nl) of cobalt (a synaptic blocking agent) into the VLM. The results demonstrated that a complete block of the increase in sympathetic nerve activity following stimulation of the IC or the LHA could be obtained with cobalt injections into the VLM. The most effective injection sites were located in the rostral ventrolateral medulla at the rostrocaudal middle and posterior regions of the C1 group of neurons. Chemical stimulation with DL homocysteic acid, in the LHA, to activate cell bodies only evoked a decrease in arterial blood pressure and sympathetic nerve activity. These responses were also blocked by cobalt injection into the VLM. Injections of cobalt into the nucleus of the solitary tract did not block sympathetic responses elicited from the LHA. These results indicate that the efferent pathway for sympathetic responses from the IC through the LHA goes to the preganglionic region of the spinal cord via a mandatory synapse in the VLM. PMID- 1415641 TI - Ca(2+)-related hepatocellular alterations during intra-abdominal sepsis. AB - Intra-abdominal sepsis was induced in rats by implanting into their abdominal cavities fecal-agar pellets impregnated with Escherichia coli and Bacteroides fragilis. Sham-operated rats received sterile pellets. A group of sterile- and septic-implanted rats was treated intraperitoneally with diltiazem (1.2 mg/kg) 8 h after implantations. Septic- and sterile-implanted rat hepatocytes were loaded with 1) the fluorescent dye indo-1 to quantify hepatocyte basal and vasopressin (100 nM)-elevated cytosolic Ca2+ concentration and 2) 45Ca to quantify Ca2+ flux and cellular content of exchangeable Ca2+. Lipid peroxidation was determined by measuring conjugated dienes (CD) and thiobarbiturate-reactive substances (TBA-RS) in liver homogenates. In septic-implanted rats, the basal cytosolic [Ca2+], cellular exchangeable Ca2+, Ca2+ flux, CD, and TBA-RS were significantly higher than in sterile-implanted rats. Although vasopressin caused a significant elevation in cytosolic [Ca2+] in septic rat hepatocytes, the magnitude of this elevation was significantly smaller than that found in the sterile group. Diltiazem treatment of septic rats significantly decreased basal cytosolic [Ca2+], cellular exchangeable Ca2+ content, Ca2+ flux, CD, and TBA-RS. Also, vasopressin-induced increase in hepatocyte cytosolic [Ca2+] in diltiazem-treated septic rats was significantly greater than that observed in untreated septic rats. Both Ca2+ and membrane lipid alterations were attenuated with diltiazem treatment of septic rats. These results suggest that prevention or attenuation of Ca2+ channel-mediated Ca2+ influx restores both Ca2+ homeostasis and membrane lipid alteration. PMID- 1415642 TI - Forced oscillations in sympathetic nerve discharge. AB - Periodic electrical stimulation of the medullary raphe or lateral tegmental field in baroreceptor-denervated cats was used to force the central systems responsible for the 10-Hz and 2- to 6-Hz rhythms in post-ganglionic sympathetic nerve discharge (SND). The 10-Hz rhythm in SND could be entrained either to the frequency of medullary stimulation or to harmonics of the stimulus frequency. The harmonic of the stimulus frequency to which the 10-Hz rhythm was entrained in one postganglionic nerve could be different from that in another nerve. On this basis, we propose that the circuits responsible for the 10-Hz rhythms in SND may be modeled as a system of coupled nonlinear oscillators, each of which either influences one postganglionic nerve or nonuniformly affects different postganglionic nerves. The relatively wide band 2- to 6-Hz component in SND could be forced into a stable oscillatory state by medullary stimulation at frequencies between 3 and 5 Hz. This observation is consistent with the view that the 2- to 6 Hz component reflects the complex behavior of a nonlinear oscillator rather than the output of a physiological noise generator. PMID- 1415643 TI - Low-dose near-celiac arterial cholecystokinin suppresses food intake in rats. AB - Exogenous cholecystokinin (CCK) suppresses food intake by acting on vagal sensory neurons. However, CCK doses used in behavioral experiments are generally much larger than those necessary to produce electrophysiological changes in vagal afferents. We made automated measurements of liquid food intake before, during, and after infusion of low doses of CCK octapeptide (CCK-8) through a chronic aortic catheter with its tip seated just above the celiac juncture. In parallel experiments, we made similar infusions while collecting blood from the hepatic portal and jugular veins for CCK assay. Injection of 10, 30, 50, and 70 pmol of CCK-8 suppressed feeding in a dose-dependent manner beginning 1 min postinfusion. The lowest dose to produce statistically significant suppression of preinfusion intake was 30 pmol. Infusion of the same CCK-8 doses into the jugular vein did not suppress feeding. Near-celiac injection of 30 pmol of CCK-8 produced systemic plasma CCK concentrations averaging 6.5 +/- 1 pM compared with less than 1 pM after saline injection. These findings show that exogenous CCK, by acting on tissues perfused by the celiac artery, can suppress feeding at doses that 1) are similar to those producing effects on the firing of vagal neurons and 2) do not increase plasma CCK concentrations above postprandial levels. PMID- 1415644 TI - Placental glucose transport in heat-induced fetal growth retardation. AB - In six ewes heat stressed from 39 to 125 days gestation and studied in a normothermic environment at 135 days, fetal and placental masses were less than in control sheep (1,645 vs. 3,112 and 149 vs. 356 g, respectively, P less than 0.01). Umbilical glucose uptakes (Rf,UP) were measured keeping maternal arterial plasma glucose at 70 mg/dl at spontaneously occurring fetal plasma glucose values (state A) and at two additional fetal glucose levels, to determine the transplacental glucose difference (delta) vs. Rf,UP relation. At normal delta of 49.2 mg/dl, Rf,UP was less in the experimental group (3.2 vs. 5.6 mg.min-1.kg fetus-1, P less than 0.05). Differences in placental perfusion and glucose consumption could not account for this result, thus indicating a reduced placental glucose transport capacity. In state A, fetal hypoglycemia enlarged significantly (P less than 0.01) the delta to 56.7 mg/dl and increased Rf,UP approximately 50% over the Rf,UP at a normal delta. In heat-induced fetal growth retardation, fetal hypoglycemia increases the flux of maternal glucose across a placenta with reduced glucose transport capacity. PMID- 1415645 TI - Muscle, joint, and tendon contributions to the torque profile of frog hip joint. AB - The relative contributions of muscle force, moment arm, and tendon compliance were determined as a function of joint angle in the frog semitendinosus-hip joint system. Muscle, joint, and tendon properties were individually measured and then combined to predict the torque generated at the hip joint as a function of joint angle (i.e., the hip torque profile). Predicted torques were then compared to experimentally measured torques using a stepwise regression model to quantify the relative importance of muscle, joint, and tendon contributions to the hip torque profile. Variation in moment arm accounted for 74% of the variability observed in the hip torque profile, while addition of the muscle's intrinsic sarcomere length tension property accounted for an additional 19% of the torque profile variability. Tendon compliance, which permitted a small amount of sarcomere shortening, accounted for only about 4% of the torque profile variability. We conclude that in this muscle-joint system, the relative fiber length-to-moment arm ratio is the major determinant of the shape of the isometric joint profile. The fiber length-to-moment arm ratio in other mammalian systems is also discussed. PMID- 1415646 TI - Both CCK-A and CCK-B/gastrin receptors are present on rabbit vagus nerve. AB - Cholecystokinin (CCK) receptors on vagal afferents have been implicated in many of the actions of the brain-gut peptide CCK, including satiety. Autoradiographic studies in rats have demonstrated the presence of CCK-A-type receptors on vagus nerves. However, direct and detailed characterization of this important CCK receptor site has never been reported with membrane-binding techniques. Using 125I-Bolt-on-Hunter-CCK octapeptide (125I-BH-CCK-8) and the recently discovered selective agonists and antagonists of CCK receptors, we have delineated the properties of CCK receptors on rabbit vagus nerve. 125I-BH-CCK-8 binding sites appeared to be homogeneous by the Scatchard analysis, with a dissociation constant of 0.14 nM and a maximum binding of 72 fmol/mg protein. However, competition studies using selective CCK ligands showed that the vagal CCK receptors are heterogeneous. A71378, a selective CCK-A agonist, showed biphasic displacement curves, with the high-affinity portion (less than 10 nM) accounting for approximately 60% and the low-affinity portion for approximately 40%. Competitive binding studies using A63387, a selective CCK-B/gastrin receptor agonist, also showed biphasic displacement curves, with the high-affinity portion (less than 30 nM) at approximately 40% and the low-affinity portion at approximately 60%. Under conditions which selectively examined vagal CCK-A or CCK B/gastrin receptors, we demonstrated that a number of CCK subtype selective agonists and antagonists possessed similar affinities for the vagal CCK-A and B/gastrin receptors as those found on the guinea pig pancreas (CCK-A) and cerebral cortex (CCK-B), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415647 TI - Effective loci and roles of acetylcholine in temperature regulation of goldfish. AB - Microinjections of acetylcholine (ACh) and carbachol were made into discrete forebrain loci in goldfish (Carassius auratus) to evaluate the importance of cholinergic mechanisms for behavioral thermoregulation. Injections of 5, 10, 25, and 50 micrograms ACh into the far anterior nucleus preopticus periventricularis (NPP) (R. Peter and V. Gill. J. Comp. Neurol. 159: 69-102, 1975) and immediately adjacent ventral telencephalon led to consistent dose-dependent decrease in selected temperature. No effect was observed following injections of 2 micrograms ACh or 0.7% NaCl. Injections of ACh into a different portion of the ventral telencephalon led to increases in the selected temperature. Lower doses of carbachol (0.5 and 1.0 micrograms) injected into the NPP produced decreases in selected temperature similar to the highest doses of ACh. Injections of ACh into loci other than those mentioned above either had no thermoregulatory effect or had lesser thermoregulatory effects which, in comparison with injections into the most effective sites, were inconsistent and required larger doses to obtain. The site where cholinergic stimulation led to decreases in the selected temperature exactly overlapped the effective site of ethanol hypothermia in the goldfish. PMID- 1415648 TI - Development of blood pressure and cardiac reflexes in the frog Pseudis paradoxsus. AB - Systemic arterial blood pressure and heart rate (fH) were measured in unanesthetized, unrestrained larvae and adults of the paradoxical frog, Pseudis paradoxus from Sao Paulo State in Brazil. Four developmental groups were used, representing the complete transition from aquatic larvae to primarily air breathing adults. fH (49-66 beats/min) was not significantly affected by development, whereas mean arterial blood pressure was strongly affected, being lowest in the stage 37-39 larvae (10 mmHg), intermediate in the stage 44-45 larvae (18 mmHg), and highest in the juveniles and adults (31 and 30 mmHg, respectively). Blood pressure was not significantly correlated with body mass, which was greatest in the youngest larvae and smallest in the juveniles. In the youngest larvae studied (stages 37-39), lung ventilation was infrequent, causing a slight decrease in arterial blood pressure but no change in heart rate. Lung ventilation was more frequent in stages 44-45 larvae and nearly continuous in juveniles and adults floating at the surface. Bradycardia during both forced and voluntary diving was observed in almost every advanced larva, juvenile, and adult but in only one of four young larvae. Developmentally related changes in blood pressure were not complete until metamorphosis, whereas diving bradycardia was present at an earlier stage. PMID- 1415649 TI - Unique electrophysiological effects of dinitrophenol in Malpighian tubules. AB - In the course of electrophysiological studies of Malpighian tubules of the mosquito Aedes aegypti, we have found unusual effects of 2,4-dinitrophenol (DNP) that offer new insights into the electrogenic and conductive properties of the tubule. DNP (10(-4)M) depolarized the basolateral membrane voltage from -58.0 to 3.3 mV, and it depolarized the apical membrane voltage from 110.6 to 8.9 mV. In parallel the transepithelial electrical resistance increased from 11.4 to 16.8 k omega.cm, and the fractional resistance of the apical membrane increased from 0.32 to 0.57. On the assumption that measures of transepithelial resistance in the presence of DNP approach the shunt resistance, the experimental results indicate the following characteristics for the equivalent circuit of the tubule: 1) a shunt resistance that is approximately one-half the transcellular resistance, 2) low and high electromotive forces, respectively, at the basolateral and apical membranes of principal cells, 3) an electrogenic pump at the apical membrane, and 4) a basolateral membrane voltage that is due mostly to the voltage developed by current flow across the basolateral membrane resistance. PMID- 1415650 TI - Ontogeny of fetal hepatic and placental growth and metabolism in sheep. AB - Ontogeny of fetal hepatic and placental growth and in vitro oxygen consumption (VO2) was investigated in fetal lambs at 75, 100, and 136 days postconception. Fetal hepatic relative weight and placental absolute and relative weights declined during this period. Oxygen consumption per gram dry weight of fetal liver and maternal placenta declined between mid and late gestation while fetal placental VO2 was unchanged. Estimated VO2 of the whole placenta did not change while the estimated total hepatic VO2 increased more than threefold between 75 and 136 days. Total hepatic VO2 was highly correlated with total placental VO2 at 136 days (r = 0.84). The results suggest that the placenta reaches its maximum growth and metabolic capacity before 100 days and possibly at or before midgestation. Changes in hepatic weight-specific total VO2, in addition to the declining relative size of the fetal liver, must contribute to the progressive decline in metabolic rate of the whole fetus during the second half of pregnancy. Correlations between placental and fetal liver weights and metabolic rates suggest the possibility of placental regulation of fetal hepatic growth and metabolism. PMID- 1415651 TI - Coordination of respiration and swallowing: effect of bolus volume in normal adults. AB - The coordination of swallowing and respiration, as measured by nasal airflow, and the effect of changes in the volume of the swallow bolus (0-20 ml) were investigated in 12 normal subjects. Both nonbolus and bolus swallows were usually preceded and followed by expiratory airflow. Swallows followed by inspiratory airflow accounted for 20% of nonbolus swallows but decreased further in frequency in the presence of a bolus. Swallowing was associated with an apneic period lasting 1.90 +/- 0.26 s for nonbolus swallows. Based on the apneic period response to bolus volume, the subjects were divided into two groups. The apneic period decreased by 60% in seven of the subjects regardless of bolus volume. The remaining five subjects gradually increased swallow apnea as bolus volume was increased. At larger bolus volumes, the latter group also exhibited an earlier onset of the swallow apnea and an increase in the number of swallows preceded by inspiration. The duration of the swallow-associated respiratory cycle was similarly prolonged by an increase in bolus volume in both groups. The results indicate that the respiratory pattern associated with swallowing is modulated by the volume of the swallow bolus. Within the normal population, at least two different patterns of response to bolus volume are identified. PMID- 1415652 TI - Arterial pressure lability and renal sympathetic nerve activity are dissociated in SAD rats. AB - The purpose of this study was to determine whether the sympathetic nervous system drives the high variability of arterial pressure (AP) observed after sinoaortic denervation (SAD) in rats. One or fourteen days after SAD, rats were instrumented chronically to record mean AP (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) in the conscious unrestrained state. Acute SAD increased MAP, HR, RSNA, and variability of MAP and decreased variability of both HR and RSNA. In rats with chronic SAD, variability of MAP remained high, whereas MAP, HR, RSNA, and variability of HR and RSNA returned to normal levels. Correlation analysis showed that, in sham-operated rats, AP and RSNA were negatively correlated in 90% of cases. In contrast, rats with both acute and chronic SAD exhibited only 30% negative and 25% positive correlations. These results indicate that 1) low AP variability in intact rats results from baroreflex-mediated inversely related fluctuations in RSNA and HR and 2) high variability of AP after acute and chronic SAD is correlated infrequently with RSNA. Because lability is reduced by interventions that block the sympathetic nervous system, we conclude that lability of AP associated with SAD appears to be mediated largely by a permissive role of sympathetic activity. PMID- 1415653 TI - Effect of physical exercise in hypobaric conditions on atrial natriuretic peptide secretion. AB - To evaluate the role of atrial natriuretic peptide (ANP) in exercise-related cardiovascular and hormonal adjustments in hypobaric conditions, 14 young athletes performed a maximal ergometer test in a hypobaric chamber adjusted to simulate the altitudes of sea level and 3,000 m. Plasma immunoreactive ANP levels rose from 5.89 to 35.1 pmol/l at sea level and rose significantly less (P less than 0.05), from 5.36 to 22.3 pmol/l, at simulated 3,000 m. Plasma immunoreactive amino-terminal peptide of proANP (NT-proANP) levels increased to the same extent at sea level and at simulated 3,000 m (from 240 to 481 pmol/l and from 257 to 539 pmol/l, respectively). Plasma immunoreactive aldosterone increased significantly less at simulated 3,000 m (P less than 0.05), but the changes in plasma renin were similar in both conditions. Plasma immunoreactive endothelin-1 and serum erythropoietin levels remained unchanged. In conclusion, we found a blunted ANP response to maximal exercise of ANP in acute hypobaric exposure compared with that in normobaric conditions, but no significant difference in the NT-proANP responses between the two conditions. The divergence may be due to stimulation of the elimination mechanism of ANP. PMID- 1415654 TI - Human IL-1 receptor antagonist partially suppresses LPS fever but not plasma levels of IL-6 in Fischer rats. AB - A human recombinant interleukin-1 receptor antagonist (IL-1ra) recognizes the two known IL-1 receptors and blocks the binding and many biological effects of both IL-1 alpha and IL-1 beta. The effectiveness of IL-1ra in modifying the fever and plasma IL-6 responses elicited by lipopolysaccharide (LPS) in vivo was tested in Fischer 344 rats. Animals that received IL-1ra 0.5 mg/kg intraperitoneally followed 10 min later by 10 micrograms/kg of LPS displayed significantly lower mean fever responses 2-4 h after injection than rats that received vehicle and LPS (0.48 +/- 0.13 vs. 0.95 +/- 0.16 degrees C, P = 0.016). Plasma levels of IL-6 at 4 h after injection were not different in IL-1ra-treated rats compared with controls (407,725 vs. 729,169 U/ml). Based on our previous finding that preadministration of antiserum to IL-1 beta markedly suppressed plasma IL-6 after LPS, and recent evidence that molar excesses of IL-1ra blocked IL-1-induced circulating IL-6 levels, the possibility that IL-1 is responsible for the induction of bioactive IL-6 during inflammation cannot be ruled out. Similarly, the inability of the IL-1ra to completely suppress the febrile responses of rats to LPS in the present study may be dose related. Alternatively, the induction of bioactive IL-6 by IL-1 in the rat may be mediated primarily through some receptor other than the type I (e.g., the type II receptor). PMID- 1415656 TI - Hypoxia attenuates the renin response to hemorrhage. AB - We studied hypoxia and hypotensive hemorrhage in conscious female goats. After control, goats continued an experimental period in normoxia or hypoxia [fractional inspired oxygen concentration (FIO2) = 0.10] for 120 min. After 60 min in the experimental period, a hemorrhage (0.5 ml.kg-1.min-1 for 30 min) was initiated (normoxic hemorrhage, NH; hypoxic hemorrhage, HH). Heart rate (HR) increased 51 +/- 18 beats/min with NH after 30 min of hemorrhage. HR increased 40 +/- 10 beats/min after hypoxic gas introduction, with no further increase during HH. Mean arterial blood pressure (MABP) was reduced 23 +/- 7 mmHg 30 min after completion of blood loss with normoxia but was reduced 23 +/- 7 mmHg at 20 min of HH. Arginine vasopressin (AVP) was increased to 2.60 +/- 2.08 and 160.40 +/- 49.74 microU/ml after 10 and 20 min of HH, respectively, and was only increased after 30 min (87.33 +/- 67.18 microU/ml) of NH. Unexpectedly, plasma renin activity (PRA) increased in parallel in both groups and was doubled at 30 min of hemorrhage. Atrial natriuretic factor was reduced to 8.8 +/- 1.6 pg/ml by 10 min of NH and to 11.4 +/- 3.3 pg/ml at 30 min of HH. Thus hypoxia leads to an earlier development of hypotension and increase in AVP with blood loss but may attenuate the PRA response to blood pressure reduction. PMID- 1415655 TI - Behavioral and tissue responses to severe phosphorus depletion in cattle. AB - Two-year-old Aberdeen Angus heifers were depleted of phosphorus (P) by loss of phosphate in saliva from a parotid gland fistula combined with a low-P diet. The inorganic phosphate concentrations (Pi) of plasma, parotid saliva, ruminal fluid, and feces were reduced, but cerebrospinal fluid Pi was unaltered. Plasma Pi fell to less than 1.0 mM in 12 wk, and the cows displayed an avid appetite for old bones. P-deficient cows preferred old weathered bones to fresh bones until the latter had aged for approximately 1.5 yr. They did not eat blood, peritoneal fat, or meat, fresh or aged for 2-3 yr. They did not eat Na or Ca phosphate salts or bone heated to greater than 250 degrees C. P-replete cows did not take or eat bones. The behavioral effects of P deficiency were associated with failure to gain body weight and maintain condition, significant bone changes indicated by reduced bone weight and specific gravity, osteopenia indicated by radiology, evidence of reduced bone formation indicated by plasma osteocalcin levels and histology, and abnormal estrous cycles. Prolonged P deficiency was associated with increased plasma concentrations of total Ca and 1,25-dihydroxyvitamin D and reduced plasma concentrations of parathyroid hormone. PMID- 1415657 TI - Regional interactions between thermosensitive neurons in diencephalic slices. AB - Rat brain slices were used to investigate regional interactions between thermosensitive neurons in different diencephalic regions. Horizontal tissue slices rested over three thermodes. This permitted independent thermal stimulation of rostral, middle, and caudal regions. Thermocouples measured tissue temperatures in these three locations, and extracellular recordings measured neuronal responses to temperature changes both locally (at the site of the recorded neuron) and in remote regions of the slice. Many of the neurons that were sensitive to remote temperatures were located near the lateral border of the diencephalic nuclei, especially in the perifornical area. All neurons displaying remote thermosensitivity also displayed local thermosensitivity. These neurons usually showed opposite responses to remote and local temperatures; i.e., most of these neurons were locally warm sensitive but showed cold sensitivity to remote temperatures. These findings indicate that thermosensitive synaptic networks extend throughout the diencephalon and may explain the effect of temperature on a variety of homeostatic systems. PMID- 1415658 TI - Delayed firing rate responses to temperature in diencephalic slices. AB - Thermoregulatory responses may be delayed in onset and offset by several minutes after changes in hypothalamic temperature. Our preceding study found neurons that displayed delayed firing rate responses during clamped thermal stimulation in remote regions of rat diencephalic tissue slices. The present study looked for similar delayed firing rate responses during clamped (1.5-10 min) changes in each neuron's local temperature. Of 26 neurons tested with clamped thermal stimulation, six (i.e., 23%) showed delayed responses, with on-latencies of 1.0 7.8 min. These neurons rarely showed off-latencies, and the delayed response was not eliminated by synaptic blockade. The on-latencies and ranges of local thermosensitivity were similar to delayed neuronal responses to remote temperature; however, remote-sensitive neurons displayed off-latencies, higher firing rates at 37 degrees C, and greater sensitivity to thermal stimulation. Our findings suggest that delayed thermosensitivity is an intrinsic property of certain neurons and may initiate more elaborate or prolonged delayed responses in synaptically connected diencephalic networks. These networks could explain the delayed thermoregulatory responses observed during hypothalamic thermal stimulation. PMID- 1415660 TI - Baroreflex control of arterial blood pressure during involuntary diving in ducks (Anas platyrhynchos var.). AB - The dynamic role of arterial baroreceptors in control of mean arterial blood pressure (MAP), heart rate (HR), cardiac output (CO), hindlimb vascular (HLVR) and total peripheral (TPR) resistance responses to forced dives was investigated in acutely and chronically barodenervated ducks. To activate the baroreflex, the proximal end of one aortic nerve was stimulated electrically with bipolar electrodes that had been implanted under pentobarbital sodium anesthesia. Predive nerve stimulation caused CO to fall (by reducing HR; stroke volume remained constant), producing a decrease in MAP to half the prestimulation level. During diving (for 2.5-min periods) nerve stimulation did not affect HR and MAP after the first minute of submersion. Neither HLVR nor TPR contributed to the fall in MAP during aortic nerve stimulation before or during diving. The effects of nerve stimulation on HR and MAP were maintained to the end of dives in animals given 100% O2 to breathe before diving. In separate experiments, increasing arterial chemoreceptor input by perfusing one vascularly isolated carotid body with venous blood caused a reduction in the effects of aortic nerve stimulation on MAP. Arterial baroreceptors may thus act on HR to alter MAP early in the dive, but as the dive progresses the baroreflex is attenuated by an increase in peripheral chemoreceptor drive. PMID- 1415659 TI - Determining energy expenditure in preterm infants: comparison of 2H(2)18O method and indirect calorimetry. AB - The doubly labeled water (2H(2)18O) method used to estimate total energy expenditure (EETotal) is particularly sensitive to analytic error in preterm infants, because of their high percentage of body water and the high ratio of water flux to CO2 production. To evaluate further use of this method, the EE of 12 preterm infants was measured by indirect calorimetry and 2H(2)18O simultaneously and continuously for 5 days. Initial infant weight, age, and postconceptional age were (means +/- SD) 1,674 +/- 173 g, 4.4 +/- 2.6 wk, and 34.6 +/- 1.6 wk, respectively. The indirect calorimeter system included an air temperature-controlled chamber and heart rate monitor. EE was measured by indirect calorimetry for 85.6 +/- 4.7% of study time and estimated from the linear regression of heart rate on EE for 14.4 +/- 4.7% of study time. The 2H(2)18O method entailed an initial dose of 100 mg 2H2O and 250 mg 18O/kg and a final dose of 75 mg 18O/kg; urine was collected twice daily. 2H and 18O enrichments were measured by gas-isotope-ratio mass spectrometry. EE was calculated from measured 2H and 18O dilution spaces (NH, NO), turnover rates (kH, kO), and measured respiratory quotient. The ratio of 2H to 18O dilution spaces was 1.01 +/- 0.01 and the ratio of kO to kH was 1.16 +/- 0.04. Estimation of EE from 2H(2)18O and indirect calorimetry agreed within 1%, although individual variability in methods was large. PMID- 1415661 TI - Tumor necrosis factor-beta induces sleep, fever, and anorexia. AB - The enhanced sleep, fever, and anorexia experienced during general infections are attributed to the increased production of cytokines. Cytokines such as interleukin-1 and tumor necrosis factor-alpha (TNF-alpha) have characteristic somnogenic, pyrogenic, and anorectic effects. TNF-beta is closely related to TNF alpha, and they share common receptors. The effects of TNF-beta on sleep-wake activity, brain temperature (Tbr), and food intake were, however, heretofore unknown. We injected 0.5-200 ng TNF-beta into rabbits intracerebroventricularly (icv) in the light period, and the electroencephalogram, movement, and Tbr were recorded for 6 h from rabbits. The highest dose, 200 ng TNF-beta, induced increases in non-rapid-eye-movement sleep and decreases in rapid-eye-movement sleep accompanied with biphasic febrile responses. Icv injection of 100 ng TNF beta at dark onset suppressed 12-h and 24-h food intake in rats. These data suggest to us that TNF-beta may belong to the group of endogenous pyrogens/sleep factors. PMID- 1415662 TI - Selective activation of norepinephrine- and epinephrine-secreting chromaffin cells in rat adrenal medulla. AB - The differential effects of insulin-induced hypoglycemia and cold exposure on adrenal medullary epinephrine (Epi) and norepinephrine (NE) cells were investigated in male Sprague-Dawley rats. In rats fasted overnight, insulin produced a marked hypoglycemia that resulted in a 70% decrease in adrenal medullary Epi content 3 h after the insulin was administered. No change in NE content was observed. Plasma Epi concentration was increased markedly after insulin, with a smaller increment in NE. In contrast, exposure to a 4 degrees C environment selectively reduced adrenal NE content, with the effect reaching statistical significance at 18 h. Cold exposure also led to a significant rise in plasma NE but not Epi. Both insulin-induced hypoglycemia and cold exposure significantly elevated adrenal dopamine, indicating that catecholamine synthesis was stimulated. Further evidence of enhanced catecholamine formation was the observation that inhibition of synthesis with alpha-methyl-p-tyrosine (AMT) greatly augmented the ability of insulin-induced hypoglycemia to selectively reduce adrenal medullary Epi content. Similarly, in cold-exposed animals, AMT pretreatment accelerated the NE depletion so that a significant decline was observed at 3 h. These results support the conclusion that the two major populations of adrenal catecholamine-secreting cells may be preferentially stimulated by different stressors. Moreover, augmented synthetic activity functions to maintain catecholamine stores in both Epi- and NE-secreting cells. PMID- 1415664 TI - Microsphere and dilution techniques for the determination of blood flows and volumes in conscious mice. AB - Although the mouse is the most commonly used transgenic species, little is known regarding cardiovascular and fluid homeostasis in this animal. Therefore, the reference microsphere and dilution techniques were adapted for the measurement of cardiac output (CO), regional blood flows, and intravascular fluid volumes in the conscious mouse. Previously acclimatized C3H mice were studied 4-5 h after surgery and recovery from anesthesia. Approximately 40,000 85Sr-labeled microspheres were injected into the left ventricle while a reference sample was withdrawn at one of two rates from the femoral artery. 51Cr and 125I were used for the determination of blood volume (BV), plasma volume (PV), and Fcells ratio (whole body hematocrit/large vessel hematocrit). CO and BV in the conscious mouse were 16 +/- 1.4 ml/min and 2.3 +/- 0.1 ml, respectively. Anesthesia lowered heart rate, blood pressure, PV, and altered the distribution of CO. Two successive injections of 15,000-20,000 microspheres were tolerated in the mouse without an increase in total peripheral resistance. The results indicate that the microsphere and indicator dilution techniques can be applied to study cardiovascular and fluid homeostasis in the mouse. PMID- 1415663 TI - Habituation of lactate release responding to stressful stimuli in rat prefrontal cortex in vivo. AB - The extracellular level of lactate is mainly dependent on functional glucose metabolism in most brain cells regulated in part by neuronal activity. We investigated the effect of environmental stimuli on lactate release in rat medial prefrontal cortex (MPFC) by in vivo brain microdialysis. Lactate release was clearly demonstrated to increase immediately and transiently from its steady state levels after various stimuli (tail pinch for 1 min, 100-dB white noise for 5 min, and immobilization for 5 min). These stimuli-induced increments were depressed after a second trial 1 h later in a manner consistent with dishabituation to a novel stimulus and "below-zero" habituation by several repetition. Likewise the local perfusion of dopamine or norepinephrine transiently increased and then diminished the second perfusion-induced increase in MPFC lactate release consistent with desensitization. These results suggest the possibility that stressful stimuli produce one-trial habituation of lactate release in MPFC via a mechanism involving the regulation of the catecholaminergic system. PMID- 1415665 TI - Alterations in oxytocin prohormone processing during early development in the fetal sheep. AB - Oxytocin (OT) prohormone processing was studied in fetal sheep. Using specific antisera that recognize the amidated and the COOH-terminal extended forms of OT, we measured arterial and venous levels of the OT peptides in fetal sheep plasma at 94 and 138 days of gestation. Plasma levels of the COOH-terminal extended forms, OT-X, were highest early in development, 35.7 +/- 9.8 vs. 14.3 +/- 5.7 pg/ml (94 vs. 138 days). The ratio of the plasma peptides, OT-X to OT, was higher in the young fetus (35 +/- 11.6 vs. 3.1 +/- 1.3, 94 vs. 138 days). There were also developmental changes in the umbilical artery-umbilical vein differences, with positive values noted in late gestation. These results demonstrate that the changes in the processing of the OT precursor that occur during fetal development are reflected by alterations in the relative amounts of prohormone and amidated hormone found in fetal plasma. PMID- 1415666 TI - Regulation of apical Cl- conductance and basolateral K+ conductances by phorbol esters in HT-29cl.19A cells. AB - The effect of phorbol esters [4 beta-phorbol 12,13-dibutyrate (PDB) and phorbol 12-myristate 13-acetate (PMA)] on potential differences and resistances was studied with the conventional microelectrode technique applied to confluent filter-grown monolayers of the human colon carcinoma cell line HT-29cl.19A. Phorbol esters (PDB or PMA from 10(-7) to 10(-6) M) evoked 1) a transient increase in the transepithelial potential difference (peak value 3.5 +/- 0.5 mV), 2) a depolarization of the cell potential by 23 +/- 2 mV at the peak of the transepithelial potential change and a continued decrease during the decline of the transepithelial potential, and 3) a decrease of the fractional resistance of the apical membrane consisting of two phases, a relative rapid one (time constant 1.2 +/- 0.2 min) and a much slower further decrease during the second phase (time constant 34 +/- 1 min). Ion replacements and electrical circuit analyses indicate that PDB activates an apical Cl- conductance and slowly inhibits the basal K+ conductance of the basolateral membrane. PDB reduced the transepithelial response to forskolin due to inhibition of the basal K+ conductance. The Ca2+ ionophore ionomycin accelerated that effect of PDB. Staurosporine inhibited the effects of PDB, suggesting that the PDB effects are mediated via activation of a protein kinase C. PMID- 1415667 TI - Novel bumetanide-sensitive K+ transport in preimplantation mouse conceptuses. AB - Ouabain-resistant K+ transport activity was characterized primarily by measuring Rb+ uptake because 86Rb+ has a more convenient half-life than 42K+. Ouabain resistant 86Rb+ uptake by mouse two-cell conceptuses and blastocysts was slowed by the K(+)-Na(+)-2Cl- cotransporter inhibitors bumetanide [inhibitory constant (Ki) = 400 nM] and furosemide (Ki approximately 10 microM), but it was insensitive to a variety of K+ channel blockers. This component of 86Rb+ transport was also inhibited by K+ and nonradioactive Rb+ and it was stimulated by Cl-. Nevertheless, neither 36Cl- nor 22Na+ uptake was inhibited by bumetanide, whereas 42K+ uptake was inhibited by both bumetanide and furosemide. Bumetanide sensitive Rb+ transport in blastocysts had a Hill coefficient of 1.0 and a Michaelis constant value of 3.0 mM. By these criteria, preimplantation conceptuses contain a novel, bumetanide-sensitive K+ transport system that does not cotransport Cl- or Na+. Moreover, bumetanide-sensitive Rb+ uptake was 10 times faster in blastocysts when they were collapsed to expose the basal membrane of the trophectoderm to 86Rb+ in the medium. Therefore, the novel system may be located predominantly in the basal rather than in the apical membrane of the trophectoderm. PMID- 1415668 TI - Carbachol induces K+, Cl-, and nonselective cation conductances in T84 cells: a perforated patch-clamp study. AB - We used the perforated patch-clamp technique to examine cell membrane ionic conductances in isolated cells of the human colonic secretory cell line, T84, during exposure to the muscarinic agonist carbachol. Carbachol (100 microM) induced both outward and inward currents when the patch pipette contained a normal intracellular-like solution, the bath contained a normal extracellular like solution, and the cells were intermittently voltage clamped between K+ and Cl- equilibrium potentials. The outward current was identified as a K+ current that averaged 483 +/- 95 pA, while the inward current averaged 152 +/- 29 pA (n = 15). The outward and inward currents oscillated with a synchronous frequency of 0.036 +/- 0.006 Hz; however, the onset of the K+ current occurred an average of 457 +/- 72 ms before the onset of the inward current. When the pipette contained a high-NaCl solution, the bath contained a Na(+)-gluconate solution, and the cells were intermittently voltage clamped between Cl- and Na+ equilibrium potentials, carbachol induced both Cl- and nonselective cation currents. The Cl- current averaged 455 +/- 73 pA, while the nonselective cation current, averaged 336 +/- 54 pA (n = 14). No difference was observed in the onset of these two currents. These results indicate that carbachol induces three separate ionic conductances in T84 cells. We used the whole cell patch-clamp technique in a previous study of these cells [D. C. Devor, S. M. Simasko, and M. E. Duffey. Am. J. Physiol. 258 (Cell Physiol. 27): C318-C326, 1990] and found that carbachol induced only an oscillating membrane K+ conductance. Thus some unidentified component of the carbachol-sensitive signal transduction pathway is diffusible and may be lost during whole cell patch clamping. PMID- 1415669 TI - Muscle fatigue in the frog semitendinosus: role of the high-energy phosphates and Pi. AB - The purpose of this study was to determine the concentration of ATP, phosphocreatine (PC), Pi, lactate, and glycogen in single frog skeletal muscle fibers and assess their role in the etiology of muscle fatigue. The frog semitendinosus (ST) muscle was fatigued, quick frozen at selected time points of recovery, and freeze-dried, and single fibers were dissected, weighed, and assayed for ATP, PC, lactate, Pi, and glycogen. The fatigue protocol reduced peak tetanic force (Po) to 8.5% of initial, while ATP and PC decreased from 45.18 to 33.16 and 128.90 to 28.76 mmol/kg dry wt, respectively. Lactate and Pi increased from 29.36 to 100.84 and 33.04 to 142.50 mmol/kg dry wt, respectively. It is doubtful that the small decline in ATP limited cross-bridge force production. Although a significant correlation between the recovery of PC and Po was demonstrated (r = 0.994), the time period showing the fastest rate of force recovery coincided with little change in PC. A significant correlation was demonstrated between the recovery of both total and the H2PO4- form of Pi and Po. In conclusion, the results of this study are incompatible with the hypothesis that the high-energy phosphates (ATP and PC) mediate muscle fatigue. The large increase in Pi with stimulation and the high correlation between the recovery of both total and the H2PO4- form of Pi and Po support a role for Pi in the production of skeletal muscle fatigue. PMID- 1415670 TI - Intracardiac detection of angiotensinogen and renin: a localized renin angiotensin system in neonatal rat heart. AB - There is increasing evidence that the renin-angiotensin system (RAS) modulates cardiovascular function through both blood-borne and tissue-derived components. The existence of a local RAS has been proposed in the heart based on biochemical and molecular biological studies that identify angiotensinogen and renin. We conducted the present study to determine the chamber localization of angiotensinogen and renin mRNA in neonatal rat heart and whether these components could be identified in cultured cardiomyocytes and fibroblasts obtained from neonatal rat heart. Experiments using polymerase chain reaction (PCR) indicated that whole hearts obtained from neonatal rats contained both angiotensinogen and renin mRNA. With the use of radiolabeled cDNA probes and in situ hybridization, angiotensinogen and renin transcripts were localized both in the atria and ventricles of neonatal rat hearts. Relative signal strengths for angiotensinogen were highest in the left and right ventricles. In contrast, renin signal strength was overall much lower and preferentially localized in the left ventricle. To investigate the cellular source of angiotensinogen and renin, cultured neonatal heart cardiomyocytes and ventricular fibroblasts were screened for angiotensinogen and renin messenger RNA and protein using PCR and indirect immunofluorescent staining, respectively. These experiments demonstrated that both cell types produce transcripts and the respective translation products for angiotensinogen and renin. These data suggest that the site of angiotensin II synthesis can occur at the level of the individual cardiomyocyte and fibroblast, where it may serve to directly and/or indirectly regulate cardiac rate, force, growth, and development in the neonate. PMID- 1415671 TI - Differential megakaryocytic desensitization to platelet agonists. AB - Platelets are released into the peripheral circulation from the bone marrow where they arise as fragments of megakaryocyte cytoplasm. To characterize the effects of platelet agonists on megakaryocytes, we examined calcium signaling and desensitization to thrombin, the thromboxane A2 (TxA2) mimetic (15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619), and platelet activating factor (PAF) in cultured CHRF-288-11 megakaryocytic cells. Initially, we compared agonist-stimulated calcium transients in fura-2-loaded CHRF-288-11 cells and human platelets. The 50% effective concentration values for the agonists to increase free cytosolic calcium were as follows: thrombin (0.11 +/- 0.02 U/ml in CHRF, 0.19 +/- 0.03 U/ml in platelets), U46619 (147 +/- 33 nM in CHRF, 157 +/- 5 nM in platelets), and PAF [15 +/- 2 nM in CHRF, 16 +/- 2 nM in platelets (n = 4 each)]. CHRF-288-11 thrombin, TxA2, and PAF receptors were demonstrated to be coupled to phospholipase C because each of the agonists stimulated phosphatidylinositol hydrolysis in myo-[3H]inositol-loaded CHRF-288-11 cells and pharmacological inhibition of phospholipase C-blunted agonist stimulated calcium signaling. CHRF-288-11 cells exposed to the three agonists for 1 h showed different patterns and extent of homologous and heterologous desensitization. Protein kinase C activation appeared to be necessary but not sufficient for desensitization because 1) activation of protein kinase C with phorbol 12-myristate 13-acetate inhibited the calcium responses to all three agonists, 2) inhibition of protein kinase C with staurosporine attenuated subsequent desensitization to each agonist, and 3) each agonist increased protein kinase C activity in CHRF-288-11 cell homogenates. PMID- 1415672 TI - Cellular mechanisms of vasopressin and endothelin to mobilize [Mg2+]i in vascular smooth muscle cells. AB - The present study was undertaken to examine the effects of arginine vasopressin (AVP) and endothelin-1 (ET-1) on cytosolic free Mg2+ ([Mg2+]i) in cultured rat vascular smooth muscle cells (VSMC). [Mg2+]i was measured using the fluorescence indicator dye mag-fura-2. AVP and ET-1 at a concentration of 1 x 10(-9) M or higher induced the mobilization of [Mg2+]i and cytosolic free Ca2+ ([Ca2+]i) in a dose-dependent manner in rat VSMC. Atrial natriuretic peptide and sodium nitroprusside producing cellular guanosine 3',5'-cyclic monophosphate did not affect [Mg2+]i and [Ca2+]i. A diterpene activator of adenylate cyclase, forskolin, also did not alter [Mg2+]i and [Ca2+]i. The removal of extracellular Mg2+ enhanced the AVP-mobilized [Ca2+]i and did not change the AVP-mobilized [Mg2+]i. The Ca(2+)-free and nominally Mg2+/Ca(2+)-free states decreased the AVP mobilized [Mg2+]i and [Ca2+]i. The Na(+)-free state enhanced the sustained, but not peak, level of the AVP-mobilized [Mg2+]i. These results indicate that AVP and ET-1 mobilize [Mg2+]i mediated through their intracellular second messenger [Ca2+]i and independent of extracellular Mg2+. Also, an increase in [Mg2+]i is indicated to stimulate the Na(+)-Mg2+ exchange to increase cellular Mg2+ efflux. PMID- 1415673 TI - Immunolocalization of chloride-transporting membrane vesicles in tracheal epithelial cells. AB - A membrane fraction eluted from a phenyl Sepharose column (MPS) was isolated from renal cortex and bovine tracheal epithelia that is enriched in a single type of Cl- channel [C. L. Preston, M. A. Calenzo, and W. P. Dubinsky. Am. J. Physiol. 263 (Cell Physiol. 32): C879-C887, 1992]. A 200-kDa membrane protein that copurifies with and appears to be specific to this fraction was purified and used to raise antisera for immunological characterization of these membranes. The antisera reacted in immunoblots with a 200-kDa protein in homogenates of bovine trachea, kidney, pancreas, lung, and intestine. There was also cross-reactivity with a 200-kDa protein in immunoblots in rat stomach, pancreas, and lung. There was no cross-reaction with rat skeletal muscle, cardiac muscle, or aorta. Thus this protein appears to be preferentially enriched in epithelial tissues. Examination of each major fraction during the purification of MPS membranes from trachea shows no enrichment of the 200-kDa protein in plasma, mitochondrial, or nuclear membrane fractions. The only significant enrichment was observed in MPS that is purified by hydrophobic chromatography. In frozen sections, antisera and monospecific immunoaffinity-purified antibodies localize the protein primarily to the apical domain of tracheal columnar epithelial cells with small punctate structures throughout the cytoplasmic compartment. PMID- 1415674 TI - Lysophosphatidic acid induces a pertussis toxin-sensitive Ca(2+)-activated Cl- current in Xenopus laevis oocytes. AB - Lysophosphatidic acid (LPA) induces a Ca(2+)-activated Cl- current in defolliculated Xenopus laevis oocytes. The response appears mediated by a specific membrane receptor, because no current is induced when related compounds [phosphatidic acid (PA), lysophosphatidylcholine (LPC), and lysophosphatidylserine (LPS)] are applied extracellularly or when LPA is injected intracellularly. Incubation in pertussis toxin prevents the response. The response is mediated by a Ca(2+)-activated Cl- current because 1) it is abolished by intracellular ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA; 5 mM) but not affected by changes in extracellular Ca2+ concentration and 2) the reversal potential becomes more positive at lower Cl- concentrations. Suramin (2 mM) blocks the LPA-induced current, but PA, LPS, LPC, and the platelet activating factor antagonist WEB-2086 do not. The response is dose dependent for LPA concentrations from 10(-8) to 10(-3) M. Incubation of oocytes in LPA does not induce germinal vesicle breakdown. These findings suggest that this novel oocyte response to LPA is mediated by a specific membrane receptor linked to a pertussis toxin-sensitive G protein. PMID- 1415675 TI - Organic osmolytes increase cytoplasmic viscosity in kidney cells. AB - The hypothesis was tested that accumulation of osmolytes by kidney cells grown in hyperosmolar media decreases the rotational and translational mobilities of small polar solutes in the cytosolic compartment. Rotational mobility was measured by the picosecond rotational correlation times (tau c) of 2',7'-bis(2-carboxyethyl) 5(6)carboxylfluorescein (BCECF) by multiharmonic microfluorimetry. In isolated segments of rabbit proximal tubule, thick ascending limb, and cortical collecting duct that were perfused and bathed in 300 mosM media, tau c were in the range 180 250 ps, corresponding to apparent rotational viscosities (eta r) of 1.1-1.5 cP. In cortical collecting tubule, eta r was not influenced by serosal vasopressin. In Madin-Darby canine kidney (MDCK) cells grown in 300-1,200 mosM media, eta r increased progressively by up to a factor of 1.38 +/- 0.03; measurements of tau c and macroscopic viscosity in artificial solutions containing osmolytes supported the hypothesis that the increased eta r was due to accumulation of organic osmolytes. BCECF translational mobility was measured by fluorescence photobleaching recovery using a focused 1.2-microns diameter Ar laser beam at 488 nm. Recovery half-times were 36 +/- 3 (SE) ms (n = 10) in MDCK cells grown in 300 mosM media and 62 +/- 3 ms (n = 10) when grown in 1,200 mosM media. The results suggest that accumulation of osmolytes by renal cells is associated with significantly increased cytosolic viscosity. The increased viscosity would slow enzymatic and transport processes in the cytosolic compartment. PMID- 1415676 TI - Vasopressin decreases immunogold labeling of apical actin in the toad bladder granular cell. AB - Studies with the confocal microscope have shown that arginine vasopressin (AVP) depolymerizes F-actin in the apical region of the toad bladder granular cell. However, the resolution of the fluorescence microscope is not great enough to reveal the exact pattern of depolymerization or the relative extent to which microvillar and subapical membrane actin pools contribute to overall depolymerization. We have developed an electron microscopic immunogold method that shows a significant decrease in immunogold labeling of actin in the region just below the apical membrane, with the decrease most pronounced in regions adjacent to the microvilli. There was no significant change of immunogold labeling within the microvilli themselves. Our studies show a reorganization of the actin cytoskeleton in the region of the granular cell, where water channel carrying vesicles are positioned and fuse in response to AVP. PMID- 1415677 TI - A plasma membrane proton ATPase in specialized cells of rat epididymis. AB - Acidification of the luminal fluid in the epididymis is believed to play an important role in sperm maturation. Previous studies have shown that specialized cells in the epithelium lining the epididymis contain high levels of carbonic anhydrase and that these cells have rod-shaped intramembraneous particles when examined by freeze fracture. Both of these features are characteristic of proton transporting intercalated cells in the kidney collecting duct. We now show that apical cells in the head of the epididymis and clear cells in the body and tail of the epididymis express high levels of a vacuolar proton-pumping adenosinetriphosphatase on their apical plasma membranes and on intracellular vesicles. By analogy with kidney intercalated cells, these cell types may be specialized for acid secretion in the epididymis. PMID- 1415678 TI - V-A and A-V modes in whole body and regional kinetics: domain of validity from a physiological model. AB - In turnover studies, both at whole body and regional level, sources of tracer and tracee are in general nonidentical thus resulting in nonuniformity of specific activity (SA). Guidelines are available in literature to deal with the heterogeneous SA problem, and either the V-A or A-V modes, based on the arterial and mixed venous blood SA, respectively, have been recommended for different substrates. In particular, the A-V mode is considered the method of choice for studying lactate, amino acids, free fatty acid, etc. Guidelines are based on specific models chosen to describe kinetic and circulatory events of the substance under study but are often conflicting. A unitary physiological framework to understand assumptions of various models is also lacking. In this paper, we first review these models to assess their domain of validity. In particular, we point out major drawbacks that relate to the tissue compartment being treated as a lumped well-mixed pool with a single SA value. We then attempt to handle the nonuniform tissue SA by employing a more physiological model. The tissue system is thought to be made up of elementary units connected in parallel and categorized according to their functional ability to affect incoming SA. Potential changes of SA within individual units are examined. Thus each tissue unit may provide a different contribution to the overall change in SA, as measured in mixed venous blood. A spatial profile of SA is also identified both along the direction of blood flow and transversely toward the inner cellular space. This distributed model allows assessment of the domain of validity of V-A and A-V modes. We show that, in general, the V-A mode underestimates the production rate both at whole body and regional level, whereas the A-V mode can either under- or overestimate it. PMID- 1415679 TI - Functional changes in salivary glands of autoimmune disease-prone NOD mice. AB - Lymphocytic infiltration of the salivary glands in autoimmune diseases results in the human condition known as xerostomia. To date, an animal model for the autoimmune development of salivary gland dysfunction has yet to be described. With the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain, salivary flow rates and total saliva protein concentration in both male and female mice showed a progressive decline in the nondiabetic and diabetic states. Submandibular gland weight decreased from control mice with the progression to onset of diabetes in both sexes, whereas the weight of the parotid gland remained unchanged. The level of saliva amylase activity, when measured relative to unit volume, decreased in nondiabetic males but increased upon onset of diabetes to control values. When expressed relative to protein concentration in saliva, amylase activity was depressed for both sets of NOD mice but was higher upon diabetes onset than in the nondiabetic animals. In females a similar pattern was observed except that amylase activity expressed relative to unit volume was not significantly depressed in either set of NOD mice. The same observations were made for glandular amylase activity. The level of epidermal growth factor (a product of the ductal cells of the submandibular gland) was reduced over 500- and 18-fold for male and female diabetic mice, respectively. Sodium dodecyl sulfate polyacrylamide gels of total saliva showed changes in mobility as well as concentration of several proteins in the NOD mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415680 TI - Effect of a high-fat diet on the incorporation of stored triacylglycerol into hepatic VLDL. AB - Triacylglycerol (TG) stored in cytoplasmic lipid droplets of hepatocytes was labeled by in vivo [1-(14)C]oleic acid injection to study the effect of a high fat diet on its incorporation into very-low-density lipoproteins (VLDL). Compared with the control diet, hepatocytes of fat-fed rats 1) contained 7.6 times more cytoplasmic (floating fat) TG and 1.9 times more endoplasmic reticulum (microsomal) TG; 2) had 8 and 6 times lower TG specific activities in cytoplasm and endoplasmic reticulum, respectively; 3) incorporated 22% less 14C label into hepatocyte esterified lipids (TG, cholesterol, phospholipid); 4) secreted 48 and 33% less radioactive and total VLDL-TG, respectively; 5) oxidized more cytoplasmic TG-fatty acid (FA); and 6) showed a 50% decreased total utilization of stored TG-FA. With both diets, the lysosomal inhibitor chloroquine concomitantly decreased productions of labeled VLDL-TG, CO2, and acid-soluble oxidation products. The decreased incorporation of stored TG into VLDL-TG appreciably contributes to the overall inhibition of hepatic VLDL secretion by fat feeding. It appears to be related to the decreased mobilization rate of stored TG and its increased channelling toward oxidation. PMID- 1415681 TI - Whole body protein metabolism and resting energy expenditure in pregnant Gambian women. AB - Whole body protein metabolism and resting energy expenditure (REE) were measured at 11, 23, and 33 wk of pregnancy in nine pregnant (not malnourished) Gambian women and in eight matched nonpregnant nonlactating (NPNL) matched controls. Rates of whole body nitrogen flux, protein synthesis, and protein breakdown were determined in the fed state from the level of isotope enrichment of urinary urea and ammonia during a period of 9 h after a single oral dose of [15N]glycine. At regular intervals, REE was measured by indirect calorimetry (hood system). Based on the arithmetic end-product average of values obtained with urea and ammonia, a significant increase in whole body protein synthesis was observed during the second trimester (5.8 +/- 0.4 g.kg-1.day-1) relative to values obtained both for the NPNL controls (4.5 +/- 0.3 g.kg-1.day-1) and those during the first trimester (4.7 +/- 0.3 g.kg-1.day-1). There was a significant rise in REE during the third trimester both in the preprandial and postprandial states. No correlation was found between REE after meal ingestion and the rate of whole body protein synthesis. PMID- 1415682 TI - Inhibition of central actions of cytokines on fever and thermogenesis by lipocortin-1 involves CRF. AB - In the present studies, the mechanisms underlying the inhibitory actions of lipocortin-1 on the pyrogenic and thermogenic properties of cytokines were investigated. Central (icv) injection of corticotropin-releasing factor (CRF, 4.7 micrograms) or the recombinant cytokines interleukin (IL)-1 alpha (50 ng), IL-1 beta (5 ng), IL-6 (20 ng), IL-8 (20 ng), or tumor necrosis factor-alpha (TNF alpha, 1 microgram) in conscious rats produced significant increases in resting oxygen consumption (VO2, 13-26%) and colonic temperature (0.7-1.6 degrees C) within 2 h postinjection. Administration (icv) of a recombinant fragment (NH2 terminus, 1-188 amino acids) of human lipocortin-1 (1.2 micrograms) produced small increases in VO2 (< 5%) and body temperature (< 0.3 degrees C). Pretreatment (-5 min) with lipocortin-1 significantly attenuated the thermogenic and pyrogenic effects of centrally injected IL-1 beta (80% inhibition), IL-6 (60%), IL-8 (80%), or CRF (60%). However, pretreatment with lipocortin-1 failed to modify the actions of IL-1 alpha or TNF-alpha. We have previously demonstrated that the pyrogenic and thermogenic effects of IL-1 beta, IL-6, and IL-8 are dependent on the central actions of CRF, whereas IL-1 alpha and TNF-alpha act independently of CRF. Fever and thermogenesis induced by all of these cytokines (with the exception of IL-8) can also be prevented by administration of a cyclooxygenase inhibitor. The data presented here suggest that the potent antipyretic effects of lipocortin-1 may result from inhibition of the release or actions of CRF rather than modulation of eicosanoid synthesis. PMID- 1415683 TI - Influence of somatotropin on lipid metabolism and IGF gene expression in porcine adipose tissue. AB - The present study was designed to evaluate the effects of porcine somatotropin (pST) treatment (2 mg/day) and dietary fat (10%) separately and in combination on the metabolic activity of subcutaneous adipose tissue, serum adipogenic activity, and insulin-like growth factor (IGF) gene expression within adipose tissue from growing 5- to 6-mo-old barrows. This study attempted to determine how these factors might contribute to the reported changes in adiposity of treated swine. Biopsies of adipose tissue were collected after 28 days of treatment following anesthesia with thiopental sodium (15 mg/kg iv). Somatotropin inhibited in vitro glucose oxidation and lipogenesis in adipose tissue but did not affect fatty acid esterification. Adipogenic activity of serum was not altered by pST treatment. Subcutaneous adipose tissue contained mRNA for IGF-I and -II, and pST administration increased the abundance of IGF-I mRNA. Dietary fat had no effect on these variables. Thus somatotropin reduces glucose metabolism in porcine subcutaneous adipose tissue. Preadipocyte proliferation and differentiation are not affected by somatotropin through its actions on systemic factors. Dietary fat provides no additional benefit in combination with pST administration to affect accretion of adipose tissue in growing swine. PMID- 1415684 TI - Role of FFA-glucose cycle in glucoregulation during exercise in total absence of insulin. AB - Muscle contraction in vitro increases glucose uptake (GU), independent of insulin, but in vivo, the exercise-induced increase in GU is impaired in insulin deficient diabetic dogs. We wished to determine whether, in vivo, suppression of the free fatty acid (FFA)-glucose cycle with methylpalmoxirate (MP, inhibitor of FFA oxidation) alone or combined with propranolol (PRO, beta-blocker) could improve GU during exercise in the absence of insulin. We performed four groups of exercise experiments (6 km/h, 10% slope) in depancreatized insulin-deprived dogs: 1) control (n = 6); 2) MP treated (5 oral doses of 10 mg/kg, twice daily, n = 6); 3) treated with MP+octanoate (OCT; oxidation unaffected by MP, 27 mumol.kg-1.min 1 iv during exercise; n = 5); and 4) MP+PRO treated (5 micrograms.kg-1.min-1 iv during exercise, n = 6). MP abolished ketosis (inhibition of hepatic FFA oxidation), decreased basal glucose production (GP), and increased metabolic clearance of glucose (MCR). During exercise, MP attenuated the increment in GP (P < 0.01), which was reversed by OCT. MP did not affect the exercise-induced increase in GU and MCR. With MP+PRO, FFAs decreased and lactate did not rise during exercise. GP was not further suppressed, but GU and MCR were increased (P < 0.01) to 89 and 31% of normal, respectively. In insulin-deprived depancreatized dogs, glucose cycling was increased to a greater extent than GP, as in type II diabetes. By the end of exercise, glucose cycling increased (P < 0.05), but to a similar extent as GP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415685 TI - Isotopomer spectral analysis of triglyceride fatty acid synthesis in 3T3-L1 cells. AB - A new analysis of stable isotope data for biosynthesis reaction, isotopomer spectral analysis (ISA), is demonstrated. ISA is theoretically applicable for polymerization biosynthesis where data are collected using selected ion monitoring gas chromatography-mass spectrometry. ISA utilizes the discrete spectrum of isotopomer abundances and the multinomial distribution to estimate two key parameters related to the biosynthesis. These parameters are 1) the dilution of the precursor immediately before biosynthesis and 2) the dilution of the newly synthesized product in the sampled compartment. Differentiated 3T3-L1 cells incorporated 2 mM [1,2-13C]acetate into triglyceride palmitate, yielding a spectrum of mass isotopomers of palmitate. The set of equations for the first nine isotopomers were solved for the two parameters using nonlinear regression. We found that precursor dilutions for acetate and glucose were constant over time, whereas the product dilution parameter increased with time, as expected for cells accumulating triglyceride palmitate. Mathematical procedures are presented for calculating 1) the predicted isotopomer fractional abundance values and 2) the correction for atoms other than the tracer atom in the mass ion. PMID- 1415686 TI - Measurement of bicarbonate turnover in humans: applicability to estimation of energy expenditure. AB - Bicarbonate turnover and energy expenditure were assessed in six healthy male volunteers, by the use of a constant infusion of radiolabeled bicarbonate (NaH14CO3) administered over 36 h, while the volunteers were confined to a whole body indirect calorimeter. Recovery and dilution of isotope were assessed from measurements made on continuous collections of CO2, entering and leaving the calorimeter, urine, and intermittent spot breath and saliva samples. Mean recovery of infused label in gaseous CO2 was 95.6 +/- 1.1% (SD) between 12 and 36 h. Applying a 95% mean recovery of label to each subject individually enabled the use of integrated mean specific activity of CO2 in spot breath and urine samples to predict measured net CO2 production and energy expenditure to within about +/- 6%. Estimates based on urinary measurements were compromised slightly by the exchange of label through the bladder wall (this was dependent on pH and volume of urine). It is concluded that this constant-infusion labeled bicarbonate method offers a potentially useful means of assessing net CO2 production and total energy expenditure over the short term (e.g., 1-3 days). PMID- 1415687 TI - Effects of differing insulin levels on response to equivalent hypoglycemia in conscious dogs. AB - The aim of this study was to determine if differing concentrations of insulin can modify the counterregulatory response to equivalent hypoglycemia. Insulin was infused intraportally into normal 18-h-fasted conscious dogs at 2 (low, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during the high dose to maintain plasma glucose similar to low (50 +/- 1 mg/dl). Despite similar plasma glucose levels, epinephrine (2,589 +/- 260, 806 +/- 180 pg/ml), norepinephrine (535 +/- 60, 303 +/- 55 pg/ml), cortisol (12.1 +/- 1.5, 5.8 +/- 1.2 micrograms/dl), and pancreatic polypeptide (1,198 +/- 150, 598 +/- 250 pg/ml) were all increased in the presence of high dose insulin (P < 0.05). Glucagon levels were similar during both insulin infusions. Hepatic glucose production, measured with [3-3H]-glucose, rose from 2.6 +/- 0.2 to 4.7 +/- 0.3 mg.kg-1.min-1 in response to high insulin (P < 0.01) but remained unchanged, 3.0 +/- 0.5 mg.kg-1.min-1, during low-dose infusions. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. By the final hour of the high-dose euglycemic clamps, cortisol (2.4 +/- 0.4 to 4.8 +/- 0.8 micrograms/dl) and norepinephrine (125 +/- 34 to 278 +/- 60 pg/ml) had increased (P < 0.05) compared with baseline. Plasma epinephrine levels remained unchanged during both series of euglycemic studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415688 TI - Effect of hyperinsulinemia on ovine fetal leucine kinetics during prolonged maternal fasting. AB - The primary effect of insulin on whole body protein metabolism in postnatal life is to reduce proteolysis. To assess the role of insulin in the regulation of protein metabolism in prenatal life, leucine kinetics were determined in the ovine fetus at baseline and in response to hyperinsulinemia. These measurements were made in each fetus in two different maternal states: ad libitum maternal feeding and after a 5-day maternal fast. Maternal fasting resulted in significant increases in baseline fetal leucine rate of appearance (Ra; 51.9 +/- 16.7 vs. 37.3 +/- 3.6 mumol/min, P < 0.05) and leucine oxidation (30.1 +/- 8.9 vs. 8.8 +/- 2.2 mumol/min, P < 0.05). Hyperinsulinemia, which was associated with significant increases in fetal glucose utilization, did not affect total fetal leucine R(a) or leucine release from fetal proteolysis in either maternal state. Under well fed maternal conditions, hyperinsulinemia produced no changes in the fetal oxidative or nonoxidative disposal of leucine. In contrast, during maternal fasting, hyperinsulinemia reduced fetal leucine oxidation (11.0 +/- 3.7 vs. 31.1 +/- 8.9 mumol/min, P < 0.05) and increased the nonoxidative disposal of leucine (35.4 +/- 4.0 vs. 19.0 +/- 6.1 mumol/min, P < 0.05). This resulted in a change in the fetal leucine accretion rate from negative to positive (-20.9 +/- 7.5 vs. 7.5 +/- 6.7 mumol/min, P < 0.05). These results suggest that, under conditions of restricted maternal substrate intake, fetal hyperinsulinemia and the attendant increase in fetal glucose utilization are associated with increased protein synthesis rather than decreased protein breakdown, thereby improving fetal leucine carcass accretion. PMID- 1415689 TI - Endocrine effects of new bombesin/gastrin-releasing peptide antagonists in rats. AB - Four new and specific pseudononapeptide bombesin/gastrin-releasing peptide (GRP) receptor antagonists, containing the D-forms of Trp or Trp analogue (Tpi) at position 6, were studied for their effects on the endocrine pancreas and GRP-(14 27)-induced gastrin release in pentobarbital-anesthetized rats. One of the analogues, D-Tpi6,Leu13-psi (CH2NH)Leu14-bombesin-(6-14) (RC-3095), was injected into the lateral brain ventricle just preceding intracerebroventricular administration of GRP-(14-27) to evaluate its antagonistic effect on GRP-induced serum growth hormone (GH) suppression. Analogues RC-3095, D-Trp6,Leu13-psi (CH2NH)Leu14-bombesin-(6-14) (RC-3125), and D-Trp6,Leu13-psi (CH2NH)Phe14 bombesin-(6-14) (RC-3420), but not D-Tpi6,Leu13-psi (CH2NH)Phe14-bombesin-(6-14) (RC-3105), significantly (P < 0.01) inhibited GRP-(14-27)-stimulated serum gastrin secretion. Analogues RC-3095, RC-3420, and RC-3105, but not RC-3125, demonstrated significant (P < 0.05) antagonistic activities on GRP-(14-27) stimulated plasma glucagon secretion. Intracerebroventricular injection of RC 3095 (10 micrograms) immediately before GRP-(14-27) (1 microgram) completely prevented the GRP-(14-27)-induced serum GH suppression. These results indicate that 1) marked differences exist in the ability of these analogues to antagonize GRP-(14-27)-induced gastrin or glucagon release, suggesting the existence of different bombesin/GRP receptor subtypes, and 2) the central effect of bombesin/GRP on GH release from the pituitary is probably mediated through specific bombesin/GRP receptors. PMID- 1415690 TI - Cyclooxygenase inhibitors blunt thromboxane action in human placental arteries by blocking thromboxane receptors. AB - The effects of cyclooxygenase inhibitors on thromboxane-mediated vasoconstriction in human placental arteries were studied in the isolated perfused fetoplacental cotyledon. The stable thromboxane agonist U-46619 caused a dose-related increase in perfusion pressure in the fetal side of the cotyledon. Meclofenamate (3.3 x 10(-5) M) significantly blunted the pressor response to U-46619, but not to angiotensin II, and inhibited thromboxane B2 formation in placental slices (IC50, 4.80 x 10(-8) M). The mechanism by which meclofenamate prevented thromboxane induced vasoconstriction was studied using ligand-binding techniques in a membrane fraction prepared from placental cotyledons. Meclofenamate caused a dose related inhibition of binding of the thromboxane receptor antagonist [3H]SQ 29548 with an IC50 of 2.61 x 10(-5) M. Scatchard analysis of equilibrium binding demonstrated that meclofenamate reduced the number of binding sites without altering the affinity of the receptor, suggesting a noncompetitive mechanism. Indomethacin also caused a dose-related inhibition of thromboxane binding (IC50, 3.27 x 10(-4) M). However, aspirin at a dose of 2.0 x 10(-3) M did not inhibit [3H]SQ 29548 binding. The data indicate that some cyclooxygenase inhibitors blunt thromboxane actions by interfering with binding at thromboxane receptor sites. These studies identify a new mechanism by which cyclooxygenase inhibition by some nonsteroidal anti-inflammatory drugs can prevent thromboxane action in fetoplacental blood vessels in vitro independent of reductions in thromboxane formation. PMID- 1415691 TI - Tissue-specific expression of bone proteins in femora of growing rats. AB - Total cellular RNA was extracted from bone cells of three different femoral compartments of 2-mo-old rats. The intact femora were first incubated with collagenase to obtain periosteal cells. The bisected periosteum-free diaphyses and metaphyses were then incubated with collagenase to obtain enriched populations of endosteal and cancellous bone cells, respectively. The total cellular RNA from these three tissues was separated by size using agarose gel electrophoresis, transferred to nylon filters, hybridized to 32P-labeled cDNA probes for glyceraldehyde-3-phosphate dehydrogenase (GAP), pre-pro-alpha (I) type I collagen (collagen), osteocalcin (BGP), and alkaline phosphatase (AP), and the cDNA/mRNA hybrids were visualized by radioautography. Bone matrix deposition was measured in each tissue compartment by tetracycline-based dynamic bone histomorphometry. The bone formation and apposition rates were greatest in the periosteum and least in metaphysis. Mean mRNA levels for collagen and BGP were positively correlated with mean bone formation and mineral apposition rates. Interestingly, mean AP mRNA levels were not correlated with indexes of bone formation. These results demonstrate that the steady-state mRNA levels for bone matrix proteins in femora show pronounced site specificity and correlate with the rates of bone matrix deposition. PMID- 1415692 TI - Concomitant interindividual variation in body temperature and metabolic rate. AB - There is significant variation in metabolic rate in humans, independent of differences in body size, body composition, age, and gender. Although it has been generally held that the normal human "set-point" body temperature is 37 degrees C, these interindividual variations in metabolic rate also suggest possible variations in body temperature. To examine the possibility of correlations between metabolic rate and body temperature, triplicate measurements of oral temperatures were made before and after measurement of 24-h energy expenditure in a respiratory chamber in 23 Pima Indian men. Fasting oral temperatures varied more between individuals than can be attributed to methodological errors or intraindividual variation. Oral temperatures correlated with sleeping (r = 0.80, P < 0.0001), and 24-h (r = 0.48, P < 0.02) metabolic rates adjusted for differences in body size, body composition, and age. Similarly, in the 32 Caucasian men of the Minnesota Semi-Starvation Study, oral temperature correlated with adjusted metabolic rate, and the interindividual differences in body temperature were maintained throughout semistarvation and refeeding. These results suggest that a low body temperature and a low metabolic rate might be two signs of an obesity-prone syndrome in humans. PMID- 1415693 TI - Ammonium chloride-induced acidosis increases protein breakdown and amino acid oxidation in humans. AB - The effect of acidosis on whole body protein turnover was determined from the kinetics of infused L-[1-13C]leucine. Seven healthy subjects were studied before (basal) and after (acid) the induction of acidosis with 5 days oral ammonium chloride (basal pH 7.42 +/- 0.01, acid pH 7.35 +/- 0.03). Bicarbonate recovery, measured from the kinetics of infused NaH13CO3, was increased in the acidotic state (basal 72.9 +/- 1.2 vs. acid 77.6 +/- 1.6%; P = 0.06). Leucine appearance from body protein (PD), leucine disappearance into body protein (PS), and leucine oxidation (O) increased significantly (PD: basal 120.5 +/- 5.6 vs. acid 153.9 +/- 6.2, P < 0.01; PS: basal 98.8 +/- 5.6 vs. acid 127.0 +/- 4.7, P < 0.01; O: basal 21.6 +/- 1.1 vs. acid 26.9 +/- 2.3 mumol.kg-1.h-1, P < 0.01). Plasma levels of the amino acids threonine, serine, asparagine, citrulline, valine, leucine, ornithine, lysine, histidine, arginine, and hydroxyproline increased significantly with the induction of acidosis. These results confirm that acidosis in humans is a catabolic factor stimulating protein degradation and amino acid oxidation. PMID- 1415694 TI - Effects of peptide YY on the human cardiovascular system: reversal of responses to vasoactive intestinal peptide. AB - Peptide YY (PYY) reverses the increased intestinal secretion stimulated by vasoactive intestinal peptide (VIP) in humans. VIP also dilates blood vessels, so we investigated the effect of PYY on the cardiovascular system. Six volunteers received PYY, 0.4 and 1.2 pmol.kg-1 x min-1 i.v. for 2 h, reproducing plasma levels seen postprandially and during a diarrheal illness, respectively. Cardiac function was assessed by echocardiography. PYY infused at 0.4 pmol.kg-1 x min-1 had no effect on cardiovascular parameters. PYY infused at 1.2 pmol.kg-1 x min-1 caused a fall in both stroke volume from 128 +/- 8 to 110 +/- 8 ml/beat (mean +/- 95 confidence interval, P < 0.01) and cardiac output from 7.2 +/- 0.4 to 6.1 +/- 0.4 l/min (P < 0.01). Effects of infusion of PYY into the brachial artery at doses of 0-16 pmol/min were assessed using venous occlusion plethysmography in six subjects. PYY infusion caused a dose-dependent fall in forearm blood flow. Six subjects received VIP, 5 pmol.kg-1 x min-1 i.v., causing a rise in heart rate from 55 +/- 3 to 70 +/- 3 beats/min and increased cardiac output from 7.3 +/- 1.1 to 13.1 +/- 1.1 l/min. The addition of PYY, 0.4 pmol.kg-1 x min-1 i.v., did not affect the heart rate significantly but decreased the cardiac output to 10.4 +/- 1.1 l/min (P < 0.01). Infusions of PYY into the brachial artery at 5 pmol/min decreased local vasodilation induced by VIP infused at 2 pmol/min at the same site by 40% (P < 0.01), even though this dose of PYY had no significant effect on local blood flow when given alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415695 TI - Differences in GH secretion from individual somatotropes in rats genetically selected for fast and slow growth. AB - A reverse hemolytic plaque assay was used to examine effects of selection for fast (F) and slow (S) growth on growth hormone (GH) secretion by individual somatotropes. Anterior pituitaries (AP) from 32 male Charles River CD strain rats selected for F and S growth for 20 generations were used. Four rats per line were used at 4, 6, 8, or 10 wk of age. Body weight (P < 0.0001) of F rats was greater compared with S rats. AP (P < 0.05) were heavier at 8 and 10 wk of age in F compared with S line rats. Percentages of GH-secreting cells were unaffected by age (range = 32.7-35.5%) and line [F = 33.1 +/- 1.2% (SE) vs. S = 34.5 +/- 1.2%] or by human GH-releasing factor (hGRF). At 8 and 10 wk, mean plaque-forming area was greater (P < 0.0001) in F compared with S rats under both nonstimulated (2,704 +/- 202 vs. 1,648 +/- 202 microns2) and hGRF-stimulated secretion (4,503 +/- 202 vs. 2,682 +/- 202 microns2). Results indicate that differences in growth observed in the two lines may be due to a greater secretory capacity of individual somatotropes rather than to a greater percentage of somatotropes or sensitivity of somatotropes to secretagogue. PMID- 1415696 TI - K+ channels in adrenal zona glomerulosa cells. I. Characterization of distinct channel types. AB - Four distinct types of K+ channels were identified in rat and bovine adrenal zona glomerulosa (ZG) cells and characterized using single-channel recording techniques. Inward rectifier channels were the most frequently observed K+ channel types in the membrane patches of both rat and bovine ZG cells. The slope conductance of the inward current was 42 pS with an extracellular K+ concentration of 150 mM. The probability of the open state of these channels increased with depolarization. With the use of inside-out membrane patches with symmetric 150 mM K+ solutions, the rectifying behavior was found to require Mg2+ on the intracellular side of the membrane. Delayed rectifier K+ channels with conductances of 27 and 48 pS were found with rat ZG cells. These channels persisted with prolonged positive voltage steps and showed long mean open times with increasing depolarization. Transient outward currents with a conductance of 28 pS were observed only in bovine ZG cells. These channels showed substantial inactivation during positive voltage steps of 250 ms duration. Ca(2+)-activated K+ channels with a large conductance (228 pS) were identified in rat and bovine ZG cells. These different classes of K+ channels may be important for the control of resting membrane potential and the generation of action potentials, thus participating in the regulation of Ca2+ influx and aldosterone secretion in ZG cells. PMID- 1415697 TI - Single K+ channels in adrenal zona glomerulosa cells. II. Inhibition by angiotensin II. AB - The effects of angiotensin II (ANG II) on single K+ channels were studied in rat and bovine adrenal zona glomerulosa (ZG) cells, using the patch-clamp technique. ANG II (0.1-10 nM) induced substantial inhibition of inward rectifier and delayed rectifier K+ channel activities in rat and bovine ZG cells. Analysis of single channel activities showed that the ANG II-induced channel-blocking effect involved reductions in the probability of the open state (Po) and the mean open time. The changes in these channel parameters occurred at all test voltages, indicating that the effect of ANG II was voltage independent. ANG II could not interact directly with the extracellular sides of the membranes in these experiments using cell-attached patches. Therefore, the effect of ANG II on K+ channels must occur through an indirect cytosolic transduction pathway. The ANG II-induced block of K+ channels will result in membrane depolarization, which may activate voltage-dependent Ca2+ channels, thereby increasing cytosolic free Ca2+ and stimulating aldosterone secretion. These channel-modulating actions of ANG II may be an important step in the initial sequence of events underlying its transduction mechanism. PMID- 1415698 TI - Metabolism of pregnant-lactating rats is adapted to pregnancy rather than to lactation. AB - In pregnant-lactating rats implantation was induced on day 4 of lactation so that, as an exception, lactation coincided with the period of high fetal growth. The already present suckling litters of these animals lagged behind in growth, but the "second" litters were at birth normal in size and weight. Such pregnant lactating rats were tested in vivo with intravenous glucose loads and compared with cyclic and lactating rats. Glucose tolerance was unaffected by the reproductive state. Pregnant-lactating rats showed, just as during their first pregnancy, low basal glucose levels. Their basal insulin levels and insulin responses, however, were decreased in comparison with the first pregnancy and resembled those of lactating rats. This may be due to an increased insulin turnover, because in vitro insulin responsiveness and insulin content of both "pregnant-lactating" and "pregnant" islets were increased in comparison with "cyclic" and "lactating" islets. It was concluded that the metabolism of pregnant lactating rats is adapted to the pregnant rather than to the lactational state. PMID- 1415699 TI - Posthepatic rate of appearance of insulin: measurement and validation in the nonsteady state. AB - To assess the accuracy with which insulin appearance rates in the peripheral circulation can be measured out of steady state, seven conscious dogs were simultaneously infused with somatostatin and insulin at known variable rates. Tritiated insulin was infused concurrently at a constant rate. Insulin rates of appearance were estimated continuously on the basis of a two-compartment model for systemic insulin kinetics. The calculations were performed assuming that insulin kinetics were linear (tracer data not used) and nonlinear or time varying (tracer data used to assess the variation). The average error in areas under the curve was -3.5 +/- 2.5 and 27.0 +/- 14.2% when nonlinear or linear kinetics were assumed. The maximal errors when linearity was assumed was 39.9 +/- 11.3% and decreased to 16.3 +/- 2.6% when the tracer data was used to account for changes in the fractional removal rate of insulin. The accuracy of the linear estimates improved as the fractional removal rate remained closer to constant. These data suggest that a priori assumptions should not be made on the linearity of the insulin system in a given experimental situation. PMID- 1415700 TI - Effect of gender on insulin resistance associated with aging. AB - To examine whether age-related changes in energy metabolism are influenced by gender, 20 females and 20 males varying in age from 21 to 80 yr were studied with euglycemic insulin clamp in combination with indirect calorimetry and infusion of [3-3H]glucose. Lean body mass (LBM) was measured with the tritiated water technique. Fat percentage correlated with age in males (r = 0.60; P < 0.05) but not in females. Although the rates of insulin-stimulated total glucose disposal and nonoxidative glucose metabolism were similar in females and males, nonoxidative glucose metabolism expressed per kilogram body weight (r = -0.64; P < 0.01) or per kilogram LBM (r = -0.46; P < 0.05) was inversely correlated with age only in males. Basal metabolic rate expressed per kilogram body weight decreased with age in both sexes, but no correlation with age was observed when data were expressed per kilogram LBM. The data clearly demonstrate different effects of age on energy metabolism in males and females. PMID- 1415703 TI - Regulation of prostacyclin production by [Ca2+]i and protein kinase C in aortic smooth muscle cells. AB - The respective roles of protein kinase C (PKC) and of cytosolic free Ca2+ concentration ([Ca2+]i) in prostacyclin synthesis were investigated in aortic smooth muscle cells by using A23187 and phorbol 12-myristate 13-acetate (PMA) to bypass the hormonal receptor. Exposure of the cells to A23187 markedly increased prostacyclin production, which was not affected by the PKC inhibitor staurosporine or by PKC depletion after prolonged incubation (48 h) of cells with PMA. The increase in [Ca2+]i induced by A23187 did not affect membranous or cytosolic PKC activity in control and PMA-stimulated cells. Activation of PKC by PMA, a weak stimulant of prostacyclin production by itself, strongly potentiated A23187-induced prostacyclin production, as well as that induced by the calcium mobilizing hormone arginine vasopressin (AVP). The potentiating effect persisted for 30 min after the removal of PMA. However, this "memory" effect was not due to sustained levels of membranous PKC activity but probably to the prolonged influence of PKC-induced phosphorylation(s). Taken together, our results suggest that, although an increase in [Ca2+]i is sufficient for inducing prostacyclin production in rat aortic smooth muscle cells, activation of PKC is necessary for AVP-induced prostacyclin production in this same tissue. PMID- 1415702 TI - Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans. AB - The present studies were performed to test the hypothesis that the liver, by increasing the synthesis of specific plasma proteins during the absorption of an amino acid meal, may play an important role in the temporary "storage" of ingested essential amino acids and to explore the effects of glucocorticosteroids and recombinant human growth hormone (rhGH) on these processes. The fractional synthetic rates of albumin and fibrinogen were determined using simultaneous infusions of intravenous [1-14C]leucine and intraduodenal [4,5-3H]leucine after 22 h fasting and during absorption of glucose and amino acids in four groups of normal subjects treated for 1 wk with placebo, prednisone (0.8 mg.kg-1.day-1), rhGH (0.1 mg.kg-1.day-1), or combined treatment. When compared with the fasted state and independent of the route of tracer delivery and hormonal treatment, albumin, but not fibrinogen, synthesis increased (P < 0.0001) during absorption of a mixed glucose amino acid meal in all groups. This increase in albumin synthesis accounted for 28% of the increase in whole body protein synthesis associated with feeding and for 24, 22, and 14% in the prednisone, rhGH, and combined treatment groups, respectively. These data suggest that the stimulation of albumin synthesis observed during feeding prevents irreversible oxidative losses of a significant fraction of ingested essential amino acids and may serve as a vehicle to capture excess dietary amino acids and transport them to peripheral tissues to sustain local protein synthesis. PMID- 1415701 TI - Fetal serine fluxes across fetal liver, hindlimb, and placenta in late gestation. AB - Eleven studies of fetal serine fluxes were performed in chronically catheterized fetal lambs by continuous infusion of [1-13C]- and [U-14C]serine into a fetal brachial vein. At tracer serine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, fetal hepatic vein, and fetal femoral vein and from the maternal femoral artery and uterine vein. Analyses were performed for plasma serine and glycine concentration, for serine and glycine 13C mole percent enrichment, and for whole blood 14CO2 and O2 concentrations. Uterine and umbilical blood flows were also measured. The placenta had a significant net uptake of fetal serine (2.1 +/- 0.5 mumol.min-1.kg-1, P < 0.01). Fetal plasma serine disposal rate (DR) was 42.5 +/- 3.9 mumol.min-1.kg-1.CO2 production from decarboxylation of fetal plasma serine represented 7.9 +/- 0.5% of DR, or 10.1 +/ 1.2 mumol CO2.min-1.kg-1. Fetal plasma glycine enrichment was 59.7 +/- 4.9% of fetal plasma serine enrichment. There was a significant loss of tracer serine from the fetal circulation into the placenta accounting for approximately 45% of infused tracer. Fifteen percent of this was converted to glycine and released into the umbilical circulation. There was a significant uptake of tracer serine by both fetal liver and fetal hindlimb with a significant CO2 production by both sites with serine oxidation predominantly in the carcass. These results indicate a high fetal serine disposal rate in the lamb, with rapid fetoplacental serine exchange, resulting in a net uptake of fetal serine by the placenta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415704 TI - Rebound elevation of fibronectin after tissue injury and ischemia: role of fibronectin synthesis. AB - Plasma fibronectin (pFn) stimulates macrophage phagocytosis of tissue debris; pFn deposition in tissues may influence vascular integrity. Although the acute depletion of pFn after surgery and/or injury has been described, less attention has been given to the rebound hyperfibronectinemia presumably "triggered" by the early pFn depletion. Using a model that compartmentalized the site of tissue injury and thus attenuated the initial pFn depletion, we studied this rebound elevation of pFn in anesthetized rats (250-350 g) after the surgical trauma of groin dissection alone (sham group) or surgery coupled with 4 h of hindlimb ischemia (experimental group). Nonoperated control rats were also anesthetized. Shams had baseline (preoperative) 6-, 8-, and 22-h postoperative pFn levels of 573 +/- 61, 598 +/- 62, 695 +/- 57, and 929 +/- 87 micrograms/ml, respectively. In the surgery-ischemia group, pFn also elevated to 1,117 +/- 40 micrograms/ml at 22 h postsurgery. Nonoperated control rats (only anesthetized) had no elevation of pFn. Intravenous infusion of gelatin-coated lipid particles (50 mg/100 g) depleted pFn by 89.3% but was unable to prevent the rebound elevation of pFn. The blood clearance of 125I-labeled pFn was very similar in control, sham, and experimental rats. In contrast, pFn synthesis over the 22-h period was dramatically altered and equal to 2.12 +/- 0.16, 3.40 +/- 0.56, and 4.49 +/- 0.17 mg pFn synthesized/100 g body wt, in control, sham, and experimental rats respectively. Thus a rapid increase in pFn synthesis contributes to the rebound hyperfibronectinemia after sublethal surgical injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415705 TI - Role of prostaglandins in regulation of gastric mucosal blood flow and acid secretion. AB - The role of prostaglandins in the rat gastric mucosal vascular response to acid stimulation was studied. Blood flow was measured with laser-Doppler flowmetry (LDF) and with red blood cell velocity measurements in the superficial mucosa; acid secretion was determined by titration. Baseline acid output was calculated to be 0.026 +/- 0.011 mueq/min. Pentagastrin (20 and 40 micrograms.kg-1.h-1 iv) significantly increased acid output to 0.387 +/- 0.104 and 0.546 +/- 0.220 mueq/min and LDF to 119 +/- 10 and 132 +/- 13% of control, respectively. LDF was significantly reduced by 15% after indomethacin (3 mg/kg iv) and was not changed by pentagastrin, whereas acid secretion increased to similar levels as without indomethacin pretreatment. The H2-agonist impromidine (100 and 500 micrograms.kg 1.h-1 iv) induced a dose-dependent increase in acid secretion (0.178 +/- 0.068 and 0.330 +/- 0.072 mueq/min, respectively) while blood flow was unchanged. Despite a substantial blood flow reduction (-38%) by indomethacin, impromidine did not alter blood flow, and acid secretion was dose dependently increased to similar values as without indomethacin pretreatment. These results provide further evidence that there is not necessarily any correlation between blood flow and acid secretion and that the pentagastrin-induced blood flow increase depends on prostaglandin release. PMID- 1415706 TI - Intestinal myoelectrical activity and transit time in chronic portal hypertension. AB - This study was designed to determine the effects of portal hypertension on intestinal myoelectrical activity and propulsion. In a single surgery, adult rats were implanted with a serosal electrode at each quarter of the small intestine, and portal hypertension was produced by calibrated constriction of the portal vein. To determine intestinal transit, portal vein-stenosed (PVS) and sham operated animals were chronically implanted with a catheter in the proximal small intestine. Transit time was determined by measuring the progression of radioactive chromium along the bowel. Studies were conducted 6, 9, and 14 days after surgical preparation. Portal hypertension was associated with both transient and persistent changes in intestinal myoelectrical activity during the experimental period. Slow wave frequency was significantly reduced in the proximal small intestine on all test days and in the distal small intestine on day 14. Occurrence of the migrating myoelectric complex was reduced on days 6 and 9. Phase III amplitude was significantly reduced in the distal small intestine on all test days. Changes in intestinal myoelectrical activity in PVS animals were not associated with measurable changes in intestinal propulsion. The results suggest that both transient and persistent changes in intestinal myoelectrical activity occur during the 2-wk period after portal vein stenosis. The functional significance of the changes is unknown. PMID- 1415707 TI - Intestinal uptake and lymphatic absorption of beta-carotene in ferrets: a model for human beta-carotene metabolism. AB - To determine the appropriateness of the ferret as a model for human beta-carotene (beta-C) metabolism, we have perfused both 15,15'-beta-[14C]C and unlabeled beta C through the upper 30-cm portion of the small intestine of ferrets in vivo. The effluents of a mesenteric lymph duct cannulation and a common bile duct cannulation, as well as portal vein blood periodically sampled via an indwelling catheter, were collected. Ten percent (9.5 +/- 0.06%) of the total administered beta-C was taken up by the intestine after a 4-h perfusion. Of the radioactivity taken up, 68.6 +/- 6.5% remained in the intestinal mucosa, 3.2 +/- 0.2% was recovered in the lymph, and 28.2 +/- 6.5% (calculated) was absorbed via the portal system. The total uptake/absorption of beta-C was 12.9 +/- 6.8 nmol.h-1.30 cm intestine-1. Large amounts of unchanged beta-C and relatively small amounts of both beta-apo-12'-carotenal and beta-apo-10'-carotenal were isolated in the intestinal mucosa after a 4-h perfusion with beta-C. Considerable amounts of metabolites more polar than retinol were formed and comprised 35% of the total radioactivity recovered in the intestinal mucosa. Polar metabolites were absorbed mostly into the portal venous system, whereas retinol and retinyl esters were absorbed mainly into the mesenteric lymph. Of the total absorbed radioactivity in lymph, 10 +/- 1.0% appeared as unchanged beta-C, with peak absorption occurring at 3 h after beginning the perfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415708 TI - Role of adenosine in postprandial and reactive hyperemia in canine jejunum. AB - The role of adenosine in postprandial jejunal hyperemia was investigated by determining the effect of placement of predigested food into the jejunal lumen on blood flow and oxygen consumption before and during intra-arterial infusion of dipyridamole (1.5 microM arterial concn) or adenosine deaminase (9 U/ml arterial concn) in anesthetized dogs. Neither drug significantly altered resting jejunal blood flow and oxygen consumption. Before dipyridamole or deaminase, food placement increased blood flow by 30-36%, 26-42%, and 21-46%, and oxygen consumption by 13-22%, 21-22%, and 26-29%, during 0- to 3-, 4- to 7-, and 8- to 11-min placement periods, respectively. Adenosine deaminase abolished the entire 11-min hyperemia, whereas dipyridamole significantly enhanced the initial 7-min hyperemia (45-49%). Both drugs abolished the initial 7-min food-induced increase in oxygen consumption. Dipyridamole attenuated (14%), whereas deaminase did not alter (28%), the increased oxygen consumption that occurred at 8-11 min. Adenosine deaminase also prevented the food-induced increase in venoarterial adenosine concentration difference. In separate series of experiments, luminal placement of food significantly increased jejunal lymphatic adenosine concentration and release. Also, reactive hyperemia was accompanied by an increase in venous adenosine concentration and release. This study provides further evidence to support the thesis that adenosine plays a role in postprandial and reactive hyperemia in the canine jejunum. PMID- 1415709 TI - Effect of putrescine on S-adenosylmethionine decarboxylase in a small intestinal crypt cell line. AB - Two key enzymes in polyamine biosynthesis are ornithine decarboxylase (ODC) and S adenosylmethionine decarboxylase (SAMDC). SAMDC decarboxylates S adenosylmethionine, which then donates aminopropyl groups for spermidine and spermine synthesis. The purpose of our study was to determine whether putrescine, taken up from medium or synthesized endogenously by ODC, alters SAMDC activity. Studies were conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Cells were grown in Dulbecco's minimal essential medium containing 5% dialyzed fetal bovine serum (dFBS). They were deprived of serum for 24 h before experiments. Basal SAMDC activity was increased significantly by > or = 10(-4) M of putrescine. Lower doses had no significant effect. The same doses of putrescine decreased ODC activity to near zero. Asparagine at 10 mM or 5% dFBS not only stimulated ODC activity and the intracellular putrescine levels but also increased significantly SAMDC activity as well. ODC activity peaked at 3 h, and the maximum level of SAMDC occurred 3-4 h after exposure to asparagine or serum. Treatment with DL-alpha-difluoromethylornithine (DFMO), a specific ODC inhibitor, prevented the increases in both cellular putrescine levels and SAMDC activity in asparagine- and serum-treated cells. In the presence of DFMO, exogenous putrescine returned SAMDC activity toward control levels but had no effect on ODC. A very slight increase of SAMDC half-life in IEC-6 cells grown in the presence of putrescine was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415710 TI - Effects of fractionated doses of ionizing radiation on colonic motor activity. AB - The colonic motor effects of fractionated irradiation were studied in five conscious dogs. Seven colonic and two ileal strain gauge transducers were implanted. After control recordings, an abdominal dose of 250 cGy was administered three times a week on alternate days for three successive weeks (total dose 2,250 cGy). Recordings were then continued for 3 wk after the completion of radiation. Colonic giant migrating contractions (GMCs) occurred at a frequency of 0.15 +/- 0.05 contractions/h in the control state. Only one of these contractions (8.3%) originated in the small bowel and propagated into the colon. Abdominal field irradiation significantly increased the incidence of colonic GMCs to 0.51 +/- 0.11 contractions/h (P < 0.05). Fifty-four percent of GMCs originated in the small intestine. GMCs during the radiation schedule were associated with explosive diarrhea on seven occasions. Irradiation did not alter the frequency of colonic migrating motor complexes, but the mean duration of contractile states decreased in the middle and distal colon. Diarrhea occurred as early as the second dose of radiation. Pathological changes in the colon were correlated with motor activity. Both small intestinal and colonic GMCs reverted to control frequencies after cessation of radiation exposure. Abdominal irradiation significantly altered the contractile activity of the colon. These changes are associated with abdominal cramping and diarrhea. PMID- 1415711 TI - Response of migrating motor complex to variation of fasting intraluminal content. AB - The characteristics of the phases of the migrating motor complex (MMC) were studied in the antrum, duodenum, and jejunum after alteration of intraluminal gas and acaloric fluid in 17 healthy volunteers. Aspiration of gas and fluid from the upper gastrointestinal tract reduced motor activity. In the antrum and duodenum, phase II contraction amplitude decreased, while in the duodenum and jejunum, the duration of phase II decreased and phase I increased. Phase III contraction frequency decreased in the duodenum only. Intragastric instillation of gas caused an increase of phase II duration and contraction amplitude in all regions. Similar effects were observed after intragastric instillation of fluid. Fasting periodic motor activity is responsive to volume changes of intraluminal gas and acaloric liquid content. PMID- 1415712 TI - Ontogeny of intestinal lactase: posttranslational regulation by thyroxine. AB - To assess the molecular mechanisms underlying the regulation of lactase ontogeny by thyroxine (T4), we performed an in vivo study of lactase catalytic activity, synthesis, subunit structure, degradation, and enterocyte migration rates in propylthiouracil-induced hypothyroid rat pups, hypothyroid pups injected with T4, and normally weaned rats. Although lactase catalytic activity remained elevated in the hypothyroid rats and declined normally in the other two groups, lactase synthesis was constant among the groups. Lactase subunit structure was identical in normally weaned and T4-injected animals, but the 100-kDa moiety, characteristic of weaned rats, was absent in the hypothyroid pups. The turnover of lactase enzyme was more rapid in euthyroid and T4-injected rats than in hypothyroid animals (t1/2 = 17, 20, and 30 h, respectively). In addition, enterocyte migration was accelerated in the T4-injected rats and reduced in the hypothyroid group compared with controls. However, transit rate was not directly related to lactase activity. Our results suggest that T4 regulates lactase ontogeny by posttranslational mechanisms that include altered processing and increased degradation of the lactase enzyme. PMID- 1415713 TI - Pharmacology of portal-systemic collaterals in portal hypertensive rats: role of endothelium. AB - The portal-systemic collateral circulation of portal hypertensive rats was studied. The collaterals were perfused through the mesenteric vein with Krebs solution, which was allowed to escape through the jugular veins. The portal collateral resistance can be quantitated from slopes of the pressure-flow relationships. In collaterals perfused at constant flow, both norepinephrine (NE) and 5-hydroxytryptamine (5-HT) increased the perfusion pressure. Phentolamine caused surmountable antagonism of the constrictor effects of NE, suggesting an involvement of alpha-adrenoceptors. The effects of 5-HT were competitively blocked by the 5-HT2 receptor-selective antagonist ICI 169,369. Isoproterenol dilated NE-preconstricted collaterals. The effect of isoproterenol was blocked by propranolol, demonstrating that the effect was mediated by beta-adrenoceptors. Acetylcholine (ACh) dilated NE-preconstricted collaterals. The dilatation effect of ACh was absent in collaterals in which the endothelium was removed. The competitive inhibitor of the nitric oxide synthase, N omega-nitro-L-arginine (L NNA), increased collateral resistance and prevented the ACh-induced dilatation of the collaterals. The constrictor response to L-NNA and the blockade of the ACh induced relaxation by both L-NNA and removal of endothelium are consistent with an involvement of nitric oxide. This experimental model can thus be used to explore the pathophysiological and the pharmacological properties of the collateral venous bed in portal hypertensive states. PMID- 1415714 TI - Diaphragmatic contribution to gastroesophageal competence and reflux in dogs. AB - Events associated with gastroesophageal reflux have been determined by concurrent diaphragmatic and esophageal body electromyography, video radiography, and manometry in four conscious dogs. Three characteristic phenomena occurred in parallel immediately before and during gastroesophageal reflux: 1) transient lower esophageal sphincter relaxation, 2) profound (99.5%) and selective inhibition of crural diaphragmatic activity, and 3) a previously unrecognized dorsal movement of the gastroesophageal junction (mean 1.3 cm) demonstrated by implanted radiological markers. The patterns associated with spontaneous acid and gas reflux were indistinguishable from those induced by gastric distension. Costolumbar diaphragmatic activity was stable up until the instant of sphincter opening, when there was a single costolumbar contraction of short duration and high amplitude. Esophageal shortening did not occur before reflux. Reflux that occurred after atropine-induced inhibition of lower esophageal sphincter tone to < 2 mmHg was intermittent and coincided with selective crural inhibition. These studies demonstrated that selective crural inhibition is a prerequisite for gastroesophageal reflux and suggest that the crural diaphragm is an important factor for the maintenance of gastroesophageal competence. PMID- 1415715 TI - Effects of NH4Cl and dimethylamine on Cl- fluxes in resting and stimulated rat submandibular acinar cells. AB - Transmembrane movements of K+ and Cl- in salivary acinar cells are important in the formation of saliva, and may be affected by changes in intracellular pH (pHi). Exposure to NH4Cl increases pHi transiently, but NH4+ may have effects independent of pHi. To investigate how Cl- transport may be altered under these conditions, rat submandibular acini were exposed to NH4Cl, and transmembrane Cl- transport was studied with 36Cl-. NH4Cl increased intracellular Cl- in these cells. The initial phase of this increase was partially HCO(3-)-dependent and was inhibited by 1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), while the sustained phase was inhibited by 0.1 mM bumetanide. NH4Cl also inhibited acetylcholine-induced Cl- efflux from tracer preloaded cells. Changes in pH did not always correlate in time or extent with those of Cl- transport. We conclude that 1) exposure to NH4Cl increases Cl-uptake primarily by a bumetanide-sensitive transport system that did not reach steady state during the experiment, 2) exposure to NH4Cl also stimulates Cl- uptake by a DIDS-sensitive mechanism, and 3) only the latter is pHi sensitive. PMID- 1415716 TI - Mouse hepatocyte membrane potential and chloride activity during osmotic stress. AB - Hepatocyte transmembrane potential (Vm) during osmotic stress responds as an osmometer, in part because of changes in membrane K+ conductance. This may contribute to the electromotive force that drives transmembrane Cl- fluxes. To test this, double-barreled ion-sensitive microelectrodes were used to measure changes in steady-state intracellular Cl- activity (aiCl) during osmotic stress applied to mouse liver slices. Hyperosmotic and hyposmotic conditions were created by rapidly switching to a solution in which sucrose concentrations were increased or reduced, respectively. Hyperosmotic stress [1.4 x control osmolality (280 mosmol/kgH2O)] decreased hepatocyte Vm 46% from -39 +/- 1 to -21 +/- 1 mV (SE; n = 16 animals). Corresponding aiCl increased twofold from 19 +/- 2 to 38 +/ 3 mM. This shifted the Cl- equilibrium potential (ECl) 19 mV, from -38 +/- 0.3 to -19 +/- 2 mV. Hyposmotic stress [0.71 x control osmolality (290 mosmol/kgH2O)] increased hepatocyte Vm 64% from -28 +/- 1 to -46 +/- 1 mV (SE; n = 13 animals). Corresponding aiCl decreased 0.53-fold from 17 +/- 1 to 8 +/- 1 mM. This shifted the ECl 20 mV from -26 +/- 2 to -46 +/- 3 mV. Thus hepatocyte aiCl is in electrochemical equilibrium with Vm. The paired measurements above were repeated after addition of K(+)-channel blockers quinine or Ba2+. Ba2+ (2 mM) had no effect on either Vm or aiCl during hyperosmotic stress; however, Ba2+ significantly inhibited changes in Vm and aiCl during hyposmotic stress. Effects of quinine (0.5 mM) on Vm and aiCl during both hyperosmotic stress and hyposmotic stress were similar to those of Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415717 TI - Vulnerability of intestinal interstitial fluid to oxidant stress. AB - The objective of this study was to quantify free radical-mediated lipid, protein, and sulfhydryl oxidation in intestinal interstitial fluid (lymph) and plasma of fasted rats. Free radicals and oxidants were generated either by thermal decomposition of 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH), which yields peroxyl radicals, or by activated polymorphonuclear neutrophils (PMNs). Incubation of intestinal lymph with AAPH resulted in a time-dependent increase in the formation of thiobarbituric acid-reactive substances (TBARS; lipid peroxidation) and carbonyl content (protein oxidation). TBARS formation was completely inhibited by removal of the apo B-containing lipoproteins in lymph suggesting that very low-density lipoprotein is the major substrate for lipid peroxidation in fasted interstitial fluid. The sulfhydryl content of lymph was reduced significantly on exposure to the peroxyl radical generator. Incubation with activated PMNs revealed qualitatively similar changes in protein and sulfhydryl oxidation; however, there was no detectable TBARS formation. Exposure of plasma to AAPH produced similar increases in protein and sulfhydryl oxidation when plasma protein concentration was adjusted to that of lymph; however, TBARS formation was significantly lower compared with lymph. Incubation of dialyzed plasma with AAPH produced significantly greater amounts of TBARS. Taken together, our data suggest that plasma is more resistant to AAPH-induced lipid peroxidation than interstitial fluid and the substrate for TBARS formation in intestinal interstitial fluid is different from that of plasma. PMID- 1415718 TI - Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy. AB - Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by partial hepatectomy (PH) modulates the process of liver regeneration, adult male rats were injected intraperitoneally with either goat polyclonal antibodies to rat tumor necrosis factor (TNF; 15 micrograms/g body wt) or an equal amount of goat anti-rat immunoglobulin G 1 h before PH. Animals were killed at 12, 24, 48, or 72 h post-PH, 1 h after injection with [3H]thymidine. Serum TNF levels were measured with the L929 cytotoxicity assay, titers of antibody to TNF were determined by enzyme-linked immunoabsorbent assay, and interleukin-6 (IL-6) concentrations were measured by B9 cell bioassay. Liver regeneration was assessed by [3H]thymidine incorporation into hepatic DNA and by immunohistochemical evidence of proliferating cell nuclear antigen (PCNA) expression. Antibodies to TNF were detected in treated rats but not in controls. Titers were highest at 12 h and progressively fell. Although TNF was never detected in serum, treatment with anti-TNF pre-PH significantly inhibited increases in serum IL-6 concentration post-PH. Anti-TNF pretreatment also inhibited [3H]thymidine incorporation into DNA, as well as expression of PCNA by both hepatocytes and liver nonparenchymal cells. These data indicate that TNF positively modulates liver regeneration after PH. PMID- 1415719 TI - Mucins: structure, function, and role in pulmonary diseases. AB - Mucins, major components of the extracellular mucus blanket that protect and lubricate mammalian epithelia, are high-molecular-mass glycoconjugates (154 to > or = 7,000 kDa) with hundreds of oligosaccharide chains in O-glycosidic linkages to a protein backbone. The apparent expression of more than one type of oligosaccharide core structure in mucins isolated from pathological material may reflect either inherent limitations in analysis, disease-related alterations in parameters affecting glycosylation and post-translational modifications (e.g., nucleotide-sugar concentrations, expression of specific glycosyltransferases, rates of transport through the endoplasmic reticulum and Golgi) or the activation of mucin protein genes that are more highly expressed in disease states with different glycosylation patterns. Recent studies have revealed the existence of a family of at least four human mucin proteins; MUC1, MUC2, MUC3, MUC4, each of which contains a variable number of tandem repeats that differ in sequence and size. Full-length sequences of cDNA clones encoding human mucin proteins are currently available only for MUC1 which, in contrast to most airway and intestinal mucins, is membrane associated and not secreted. Current information on mucin oligosaccharides and proteins is reviewed herein. More detailed knowledge of the protein and oligosaccharide structures of mucins will be important in identifying specific role(s) in health and disease, i.e., in the physiological functions of mucus. PMID- 1415720 TI - H2O2 injury causes Ca(2+)-dependent and -independent hydrolysis of phosphatidylcholine in alveolar epithelial cells. AB - Oxidants may play a central role in the pathogenesis of adult respiratory distress syndrome, and phospholipase activation is a potential mechanism of oxidant-induced injury of alveolar epithelial cells. Studies were performed in rat alveolar type II epithelial cells (RAEC) after 3 days in culture. As measured by 51Cr and lactate dehydrogenase release, H2O2 caused time- and dose-dependent cytotoxicity to RAEC. RAEC phospholipids labeled with [14C]-stearic acid ([14C]SA) and [3H]arachidonic acid ([3H]AA) released free fatty acids in response to H2O2 in a manner that closely paralleled the cytotoxicity indexes. Analysis of phospholipid subclasses indicated that phosphatidylcholine was preferentially affected. Analysis for putative products of phospholipase activity revealed significant increases in diacylglycerol and phosphorylcholine, expected products of phospholipase C, as well as significant increases in L-alpha lysophosphatidylcholine and L-alpha-glycerophosphocholine, expected products of phospholipase A2. Increases in phospholipase D activity were not detected. To determine whether H2O2-stimulated phospholipase activity might be Ca2+ stimulated, RAEC were loaded with fura-2/AM, and changes in intracellular Ca2+ concentrations ([Ca2+]i) were monitored by epifluorescent microscopy. Exposure to H2O2 caused elevations in [Ca2+]i, and the time and dose relationships were consistent with the hypothesis that the release of [14C]SA and [3H]AA is related to changes in cellular Ca2+ concentrations. Additionally, pretreatment with MAPTAM, an intracellular chelator of calcium, partially blocked H2O2-mediated [3H]AA liberation. However, experiments in saponin-permeabilized RAEC, in which [Ca2+]i was strongly buffered by ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid, indicate that H2O2-induced phospholipase activity also has a Ca(2+)-independent component.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415721 TI - Respiratory activity of lung mitochondria isolated from oxygen-exposed rats. AB - The effects of in vivo oxygen exposure on mitochondrial energy metabolism were assessed by measurements of ADP-stimulated rates of oxygen utilization in lung homogenates and mitochondria isolated from rats after 24 h of exposure to 100% oxygen. Oxygen utilizations supported by FAD-linked metabolism of succinate and alpha-glycerophosphate were unaffected by oxygen exposure. On the other hand, mitochondrial respiratory activities supported by the NAD-linked substrates, isocitrate and alpha-ketoglutarate, were significantly reduced by 32 and 25%, respectively. These results could not be explained by changes in mitochondrial pyridine nucleotide or calcium contents. The activity of mitochondrial isocitrate dehydrogenase, measured in the absence of respiratory chain activity, was shown to be unaltered by oxygen exposure, suggesting that a potential site of oxygen induced impairment is located within the respiratory chain rather than at the enzyme site of reducing equivalent transfer from NAD to components of the respiratory chain. Because lung mitochondrial alpha-glycerophosphate dehydrogenase activity was unaffected by oxygen exposure, it may maintain the oxidation of cytosolic reducing equivalents and subsequent energy generation under conditions when NAD-linked proton-shuttle mechanisms are impaired. PMID- 1415722 TI - Intact lung cytochrome P-450 is not required for hypoxic pulmonary vasoconstriction. AB - Lung cytochrome P-450 has been suggested to play a role in hypoxic pulmonary vasoconstriction. We reexamined this hypothesis using specific suicide substrate inhibitors of cytochrome P-450, 1-aminobenzotriazole (1-ABT), and chloramphenicol. In isolated, blood-perfused rat lungs, 1-ABT (0.5 mg/ml) and chloramphenicol (1 mg/ml) inhibited lung microsomal cytochrome P-450 (ethoxycoumarin O-deethylase) activity to 24 and 44% of control, respectively, and blunted hypoxia and angiotensin II-induced vasoconstriction. The depression of vascular contraction by 1-ABT was not due to an effect on calcium channels, since similar concentrations of 1-ABT had no inhibitory activity on electrical field-stimulated contractile response in rabbit papillary muscle strips. However, when 1-ABT was washed out of the lung after preincubation, the vascular reactivity to hypoxia and angiotensin II was restored despite persistent depression of lung cytochrome P-450 activity to 26% of control values. In isolated rat aortic and pulmonary arterial rings, addition of 1-ABT or metyrapone to the organ bath acutely reversed norepinephrine-induced contraction but preincubation with 1-ABT, metyrapone, or chloramphenicol had no effect on subsequent norepinephrine contractions. We conclude that 1-ABT inhibited lung vascular reactivity by a mechanism independent of cytochrome P-450 inhibition or calcium channel blockade and that an intact lung cytochrome P-450 system is not required for hypoxic pulmonary vasoconstriction in rat lungs. PMID- 1415723 TI - Influence of growth oxygen level on eicosanoid release from lung endothelial cells during hypoxia. AB - Eicosanoid products of arachidonic acid are suspected modulators of hypoxic vasoconstriction in the pulmonary vasculature. Vascular endothelial cells (EC) release several eicosanoids, but there is disagreement regarding the effect of hypoxia on EC eicosanoid release. We postulated that the oxygen level of growth in culture might influence the release of eicosanoids during acute hypoxia. We studied EC cultured from the main pulmonary arteries of pigs and grown at either 5% or near 20% oxygen, representing the normal limits of oxygen exposure to endothelium in normal lungs. Although cultures grown in 5% oxygen grew slightly faster by 4 days, the confluent cell number, protein content, and baseline eicosanoid release were no different compared with paired cultures grown in 20% oxygen. However, with an acute decrease in oxygen level, cultures grown in 5% oxygen released less prostaglandin E2, F2 alpha, and 6-ketoprostaglandin F1 alpha compared with amounts released at the growth oxygen level. In contrast, cultures grown in 20% oxygen released increased amounts of these eicosanoids compared with release at the growth oxygen level. Release of thromboxane B2 was not significantly different during hypoxia between cultures grown at 5% vs. 20% oxygen. In other experiments, cyclooxygenase activity, stimulated arachidonic acid release by calcium ionophore A23187, and uptake of arachidonic acid were no different in cultures grown at 5% vs. 20% oxygen. However, arachidonic acid release during hypoxia was reduced in 5% cultures and increased in 20% cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415724 TI - Rat lung antioxidant enzymes: differences in perinatal gene expression and regulation. AB - The lung activity of the antioxidant enzymes (AOEs) copper, zinc superoxide dismutase (Cu,Zn SOD), catalase (CAT), and glutathione peroxidase (GP), but not manganese superoxide dismutase (Mn SOD), increases in rats during late gestation; the concentrations of Cu,Zn SOD mRNA and CAT mRNA also rise. During early postnatal exposure to > 95% O2, the lung activity of Cu,Zn SOD, CAT, and GP increases. We now show 1) the lung concentration of Mn SOD mRNA and GP mRNA does not increase in late gestation; 2) Mn SOD activity and the concentration of its mRNA and of GP mRNA increase during exposure of neonatal rats to > 95% O2; and 3) as previously shown for CAT mRNA, the increase in lung concentration of the mRNAs for Cu,Zn SOD, Mn SOD, and GP during early postnatal hyperoxia occurs with a 70 80% prolongation of the half-life of these mRNAs. We conclude that 1) in late gestation the level at which lung AOE gene expression is regulated differs among the enzymes, 2) the level at which lung AOE gene expression is regulated shortly after birth in response to > 95% O2 is uniform among the enzymes, and 3) the lung's AOE response to neonatal hyperoxia is not merely a step-up of its prenatal regulation but involves different regulatory mechanisms based on increased stability of AOE mRNAs. PMID- 1415725 TI - Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages. AB - Studies suggest smokers have decreased alveolar macrophage (AM) accessory cell (AC) function and a reduced incidence of immune-mediated lung diseases such as sarcoidosis. Impaired AM secretion of cytokines important in T-cell immune responses could explain this observation. We investigated production and secretion of interleukin-1 (IL-1) and interleukin-6 (IL-6) in smokers and nonsmokers. Lipopolysaccharide-induced AM IL-1 secretion in smokers was significantly reduced compared with nonsmoker AM. However, intracellular IL-1 in smoker AM was higher than in nonsmokers, suggesting that reduced IL-1 secretion was due to impaired release rather than reduced production. Smoker AM secreted significantly less bioactive IL-6 measured in a bioassay compared with nonsmoker AM. Intracellular IL-6 was virtually undetectable in both groups. In some smokers IL-6 production determined by immunoprecipitation was reduced. However, as a group antigenic IL-6 secretion determined by enzyme-linked immunoabsorbent assay was similar in smokers and nonsmokers, suggesting that smoker AM may cosecrete an inhibitor of IL-6 bioactivity. Indeed, AM supernatants from smokers inhibited B9 proliferation in response to maximal recombinant IL-6 stimulation, whereas supernatants from nonsmokers did not. We conclude that AM from smokers secrete less cytokines important in T-cell proliferation than AM from nonsmokers and suggest that for IL-6 this impairment is related to both decreased production of antigenic protein as well as cosecretion of an IL-6 inhibitor. PMID- 1415726 TI - Intracellular processing of pulmonary surfactant protein B in an endosomal/lysosomal compartment. AB - The hydrophobic surfactant protein B (SP-B) is synthesized in alveolar type II cells as a 40-kDa precursor protein that is processed via 39- and 23-kDa intermediates to the mature 8-kDa size. To determine the site of SP-B processing, the subcellular distribution of the precursor and mature forms of SP-B was investigated on ultrathin cryosections of human lung using two polyclonal antibodies that discriminate between precursor forms and the mature form of SP-B. An antibody against the human lysosomal membrane glycoprotein CD63 was used to identify organelles in the endosomal/lysosomal pathway. Precursor SP-B was present in the endoplasmic reticulum, the Golgi complex, and multivesicular bodies but was absent from lamellar bodies and plasma membrane. Mature SP-B was present in multivesicular bodies and lamellar bodies but almost completely absent in the endoplasmic reticulum and the Golgi complex. Semiquantitative evaluation of the immunogold labeling by counting the gold particles representing precursor or mature SP-B in the different compartments showed that the mature-to-precursor ratio was low in the endoplasmic reticulum and the Golgi complex (0.13 and 0.11, respectively), increased in the multivesicular bodies to 3.4, and was very high (65) in lamellar bodies. Multivesicular bodies and lamellar bodies contain the lysosomal membrane marker CD63 and are therefore part of the lysosomal pathway. These data strongly suggest that precursor SP-B is proteolytically processed to its mature 8-kDa form intracellularly in an endosomal/lysosomal compartment, most probably in multivesicular bodies. PMID- 1415728 TI - Differential effect of platelet-derived growth factor on glycosaminoglycan synthesis by fetal rat lung cells. AB - Lung morphogenesis is in part regulated by extracellular matrix (ECM), and cytokines may indirectly control lung development via modulation of ECM. In the present study, we investigated the effect of different platelet-derived growth factor (PDGF) isoforms AA, AB, and BB on the synthesis of glycosaminoglycans (GAG) by fetal rat lung cells. Independent of gestational age, PDGF-BB, but not PDGF-AA or -AB, stimulated GAG synthesis of fetal lung fibroblasts. In contrast, GAG synthesis by epithelial cells was not affected by any of the PDGF molecules. The stimulatory effect of PDGF-BB on fibroblast GAG biosynthesis was dose (> 10 ng/ml) and time (> 8 h) dependent. The relative proportion of the individual GAG molecules was not altered by PDGF-BB exposure. Blockage of tyrosine kinase activity with staurosporine did abolish the effect of PDGF-BB on fibroblast GAG formation. Actinomycin D and cycloheximide did not abrogate the PDGF-BB effect, suggesting that no new RNA or protein synthesis is required. The proteoglycan synthesis blocker, beta-D-xyloside, also did not inhibit the PDGF-BB action on fibroblast GAG synthesis. These data suggest that the effect of PDGF on GAG synthesis is cell type and isoform specific and is most likely a direct effect on the GAG chain elongation enzymes. PMID- 1415727 TI - Mechanisms of fibrin formation and lysis by human lung fibroblasts: influence of TGF-beta and TNF-alpha. AB - Fibrin gels form within the alveolar and interstitial compartments of the injured lung, and fibroblasts invade and facilitate organization of these transitional gels. We studied the effects of transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) on fibrinolytic and procoagulant activities of human lung fibroblasts (HLF) to determine their capacity to regulate pulmonary fibrin deposition. Fibrinolytic activity of cell lysates and media (n = 6 HLF cultures) were uniformly depressed by TGF-beta or TNF-alpha. In dose and time-course studies, HLF plasminogen activator inhibitor-1 (PAI-1) was increased by TGF-beta, whereas TNF-alpha induced release of PAI-1 into the media. HLF and media urokinase concentrations were depressed by TGF-beta, whereas urokinase was unchanged or increased by TNF-alpha. Tissue plasminogen activator was mainly cell associated and unchanged by TGF-beta or TNF-alpha. HLF antiplasmin activity was not detected. Plasma recalcification times of HLF media were decreased by TNF-alpha but unchanged by TGF-beta. These studies suggest that TGF-beta and TNF-alpha impair the ability of HLF to degrade fibrin by disturbing the balance of HLF plasminogen activators and PAI and that these cytokines concurrently leave unchanged or increase the capacity of HLF to initiate fibrin formation. Cytokines likely to occur in the injured lung induce abnormalities of fibrinolysis in HLF from adults; such abnormalities favor extravascular fibrin deposition, a characteristic feature of alveolitis. PMID- 1415729 TI - ANF inhibits norepinephrine-stimulated fluid absorption in rat proximal straight tubules. AB - We have previously shown that atrial natriuretic factor (ANF) only inhibits fluid absorption in the proximal straight tubule after the tissue has been exposed to angiotensin (ANG) II. In this paper, the interaction between ANF and norepinephrine (NE) in the proximal straight tubule was investigated. ANF alone (10(-9) M) added to the bath had no significant effect on fluid absorption. In contrast, when tubules were first treated with 10(-7) M NE, 10(-9) M ANF reduced fluid absorption from 0.63 +/- 0.09 to 0.41 +/- 0.04 nl.mm-1.min-1. NE alone stimulated fluid absorption by 33%. Dibutyryl-guanosine 3',5'-cyclic monophosphate (cGMP; 50 microM) mimicked the effects of ANF, reducing fluid absorption from 0.73 +/- 0.06 to 0.35 +/- 0.07 nl.mm-1.min-1 in NE-treated tubules. However, it had no effect on fluid absorption in the absence of NE. These studies suggest that 1) ANF can regulate fluid absorption in the proximal nephron; 2) this inhibition occurs only after transport has been stimulated by agents such as NE (or ANG II); 3) cGMP is part of the second messenger system of ANF in the rat proximal straight tubule; and 4) the primary interaction between ANF and NE (or ANG II) occurs in the second messenger cascades subsequent to steps that affect levels of cGMP. PMID- 1415730 TI - Effect of cold exposure and nutrient intake on sympathetic nervous system activity in rat kidney. AB - Renal sympathetic nervous system (SNS) responses to environmental temperature and diet were evaluated using [3H]norepinephrine ([3H]NE) turnover as the index of sympathetic activity. Pharmacological studies first demonstrated that renal NE was localized principally within storage granules of renal sympathetic nerves and regulated by central sympathetic outflow. Acute exposure to cold (4 degrees C), which increased cardiac SNS activity (P < 0.00005), had no effect on renal SNS. A 48-h fast suppressed renal [3H]NE turnover by 37% (P = 0.00024) and cardiac [3H]NE turnover by 48% (P = 0.00608). Dietary supplementation with sucrose did not affect [3H]NE turnover in kidney in either of two separate experiments, although it increased cardiac NE turnover in both. On the other hand, lard feeding significantly increased [3H]NE turnover in both kidney and heart, whereas dietary protein supplementation exerted no effect on either renal or cardiac [3H]NE turnover. These studies demonstrate a unique pattern of sympathetic regulation in kidney, one which is highly responsive to fasting and dietary fat, but not to cold exposure or dietary sucrose. PMID- 1415731 TI - Effects of dietary protein and salt on rat renal osmolytes: covariation in urea and GPC contents. AB - Renal medullary cells contain high levels of (glycine) betaine, glycerophosphorylcholine (GPC), myo-inositol, and sorbitol. Two functions of these have been proposed: 1) that they are compatible osmolytes which regulate cell volume (against high external NaCl) without inhibiting proteins and 2) that methylamines (GPC and betaine) are counteracting osmolytes which stabilize proteins against perturbation from high renal urea. As a test of the latter, osmolyte contents in kidney medullas were measured in rats subjected to three types of dietary manipulation: 1) diets with protein and NaCl contents varied oppositely, 2) diets with a constant low NaCl and varied protein content, and 3) a low-calorie diet. With low-protein and low-calorie diets, only renal contents of urea, GPC, and inositol decreased; betaine and sorbitol contents increased such that contents of total nonurea organic osmolytes remained constant. With high-protein diets, only renal contents of sodium, urea, and GPC increased, with the latter giving total organic osmolytes a consistent correlation to sodium. Across all diets, the only consistent (linear) correlations were 1) between urea and GPC contents, supporting previous suggestions that GPC is the major counteractant to urea, and 2) between total organic osmolytes and sodium (but not urea) contents, as predicted by the compatible osmolytes hypothesis. PMID- 1415732 TI - Intrarenal handling of proteins in rats using fractional micropuncture technique. AB - Previous micropuncture studies on protein handling along the nephron could not exclude the possibility of contamination by extratubular proteins. Thus we developed a fractional micropuncture method. Renal tubules were punctured with an outer puncture pipette, into which an inner collection pipette was inserted repeatedly to collect tubular fluid, usually up to four fractions. The albumin concentration of tubular fluid was highest in the first fraction and gradually decreased to a constant level, indicating physiological albumin concentrations. On the other hand, low-molecular-weight protein (LMWP) concentrations showed no significant difference among the four fractions. By plotting the protein delivery in the fourth fraction along the nephron, glomerular filtrated protein concentrations were estimated by extrapolating the tubular fluid-to-plasma inulin concentration ratio into one. The glomerular filtrated albumin was 22.9 micrograms/ml (0.00062 in filtration coefficient), and that of LMWP was 72.1 (0.988). Albumin was almost evenly reabsorbed in early (37%) and late (34%) proximal convoluted tubules and the straight tubules (23%). On the other hand, LMWP was more strongly reabsorbed in the early proximal convoluted tubules (54%) than in the late ones (28%) or the straight portion (5%). The fractional micropuncture procedure provides direct evidence of protein handling along the nephron without extratubular protein contamination. PMID- 1415733 TI - Endothelin-1 is an autocrine factor in rat inner medullary collecting ducts. AB - Endothelin-1 (ET-1) may be an important factor in the regulation of inner medullary collecting duct (IMCD) physiology. This segment of the nephron synthesizes ET-1, expresses endothelin receptors, and responds to exogenous ET-1 by reducing Na(+)-K(+)-ATPase activity and water transport. Taken together, these findings suggest an autocrine role for ET-1 in the regulation of IMCD function; however, because of the polarized nature of the IMCD, it is not known if ET-1 secretion, receptors, and receptor activation occur on the same side of the cell. To examine this question, rat IMCD cells were grown to confluence on semipermeable membranes. These cells exhibited polar morphology with high transepithelial electrical resistances. Immunoreactive ET-1 was secreted primarily into the basolateral side. Furthermore, 125I-ET-1 bound predominantly to the basolateral surface. Finally, ET-1 (10(-8) M) stimulated prostaglandin E2 production only when added to the basolateral side. These data indicate, therefore, that ET-1 is capable of autocrine regulation of IMCD cells and that this effect occurs predominantly on the basolateral side. PMID- 1415734 TI - Effect of vasoactive agents on induction of Egr-1 in rat mesangial cells: correlation with mitogenicity. AB - The early growth response gene 1 (Egr-1) is a member of the family of immediate early response genes. Egr-1 encodes a nuclear phosphoprotein that binds a specific nonameric DNA sequence through three zinc-finger domains and functions as a transcriptional activator. We tested whether the vasoactive agents platelet derived growth factor (PDGF), arginine vasopressin (AVP), serotonin (5-HT), and angiotensin II (ANG II) induced Egr-1 mRNA in cultured rat mesangial cells (MCs) and investigated the role of protein kinase C (PKC) in mediating the induction process. PDGF, AVP, and 5-HT induced Egr-1 mRNA within 15 min, reaching peak levels at 45-60 min. After PDGF and 5-HT stimulation, Egr-1 mRNA levels returned to baseline within 4 h, whereas AVP induced a sustained increase for up to 8 h. There was a very close correlation between doses required for Egr-1 induction and induction of MC proliferation. ANG II was a very weak MC mitogen and induced only a small increase in Egr-1 mRNA. Comparison of control cells with cells depleted of PKC by 48 h of PMA treatment revealed that induction of Egr-1 by PDGF and 5-HT is independent of PKC. In contrast, however, the Egr-1 response to AVP was diminished in PKC-depleted cells. AVP induced Egr-1 mRNA 10.9-fold in control cells, compared with 7.8-fold in PKC-depleted cells. Egr-1 mRNA after AVP stimulation remained elevated in control cells for up to 8 h but returned to baseline after 120 min in PKC-depleted cells. Similar results were obtained using the PKC-inhibitor H-7. Using immunocytochemistry, PDGF and AVP were found to induce Egr-1 protein within 30 min localized to the nucleus. We conclude that there is a strong correlation between induction of Egr-1 after stimulation with PDGF, AVP, 5-HT, and ANG II and the proliferative response elicited by these agents in MCs. AVP induces Egr-1 by both PKC-dependent and PKC-independent pathways, whereas the effects of PDGF and 5-HT are independent of PKC. PMID- 1415735 TI - Reversal of Na+ retention in chronic caval dogs by verapamil: contribution of medullary circulation. AB - The effects of verapamil on papillary plasma flow (PPF) and Na+ excretion were studied in anesthetized chronic caval dogs with low cardiac output and Na+ retention. Infusion of verapamil into the left renal artery (5 and 10 micrograms.kg-1.min-1) caused a dose-dependent ipsilateral increase in renal blood flow and Na+ excretion (from 10 +/- 2 to 171 +/- 32 and 225 +/- 35 mu eq/min, respectively). PPF in the left kidney was 26.6 +/- 4.4 and was significantly greater than that measured in the contralateral kidney (13.3 +/- 2.4 ml.min-1.100 g-1) (P < 0.01). The natriuresis occurred independent of changes in cardiac output and peripheral vascular resistance. In a separate group of caval dogs in which stimulation of the renin-angiotensin and adrenergic systems was intensified with a tighter caval constriction, verapamil failed to induce renal vasodilation or natriuresis and PPF was not altered. Despite the disparate hemodynamic responses, verapamil stimulated renal production of both renin and prostaglandin E2 in both groups of caval dogs. We conclude that the ability of verapamil to induce papillary vasodilation may contribute to the natriuresis seen in the caval dog, in which the site of Na+ retention includes the loop of Henle. PMID- 1415736 TI - Diabetic rat glomerular mesangial cells display normal inositol trisphosphate and calcium release. AB - Since diabetes may cause cellular myo-inositol depletion, we investigated whether the observed in vitro hypocontractile response of streptozotocin (STZ)-treated rat glomeruli to angiotensin II (ANG II) is associated with an alteration in inositol trisphosphate (IP3) mobilization of intracellular Ca2+. Contraction of diabetic isolated glomeruli induced by ANG II (5 microM), measured in vitro by changes in the planar area, was reduced by 60%, compared with normal up to 60 min (P < 0.05). In cells of isolated glomeruli, preloaded with myo-[3H]inositol, production of [3H]inositol phosphates ([3H]IPs) and [3H]inositol trisphosphate ([3H]IP3) was analyzed by Dowex chromatography. ANG II (1 microM) evoked an immediate peak (5-10 s) in total [3H]IPs of 60.5 +/- 18.8% (mean +/- SE) above basal (nonstimulated state) in normal glomeruli, and 88.4 +/- 19.4% in diabetic condition [not significant (NS), n = 8]. At 60 s, the normal and diabetic total [3H]IPs responses were not significantly different from each other. The immediate (10 s) [3H]IP3 response from normal glomeruli, 8.1 +/- 7.9% above basal, was not significantly different from that of diabetic glomeruli, 15.7 +/- 7.4%. ANG II receptor-mediated rise in cytosolic Ca2+ in the cells of normal and diabetic isolated glomeruli was compared by measuring the efflux of 45Ca2+. Isolated glomeruli were preloaded with 45Ca2+. Following ANG II stimulation, peak 45Ca2+ efflux values at 1 min were 141.7 +/- 15.9% (normal) vs. 143.7 +/- 7.8% (diabetic) of baseline (100%), respectively (NS, n = 4). Thapsigargin, 2 microM, specifically prevented ANG II-stimulated and IP3-mediated 45Ca2+ efflux (73% inhibition, P < 0.001) from cells of whole glomeruli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415737 TI - Involvement and source of calcium in volume regulatory decrease of collapsed proximal convoluted tubule. AB - We examined the role of Ca2+ in the volume regulatory decrease (VRD) of rabbit collapsed proximal tubules. Reduction of bath osmolality by 125 mosmol/kgH2O led to an initial cell swelling of 62.3 +/- 7.5% followed by a partial regulatory phase bringing cell volume to a value of 13.3 +/- 2.9% above control (n = 5). This swelling was accompanied by a transient intracellular Ca2+ ([Ca2+]i) increase from 174 +/- 33 to 306 +/- 67 nM (P < 0.05, n = 8). In the same condition, but in absence of extracellular Ca2+ ([Ca2+]e) [1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA)], VRD following hypotonic shock was identical to that observed in presence of [Ca2+]e (n = 5), and [Ca2+]i increased transiently from 136 +/- 29 to 161 +/- 31 nM (P < 0.05, n = 5). Addition of 100 microM 8-(N,N-dimethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8), an agent known to inhibit Ca2+ release from intracellular stores, did not affect the initial cell swelling (63.4 +/- 4.2%), and VRD occurred to the same extent (25.0 +/- 7.1%, n = 4), although at a lower rate. In these conditions, [Ca2+]i, which was 113 +/- 30 nM in the isotonic solution, decreased progressively to 81 +/- 20 nM over the 5-min hypotonic period (n = 5). Mere preincubation with 100 microM TMB-8 before hypotonic shock led to a VRD identical to that observed in presence of Ca2+ and absence of TMB-8 while still blocking the Ca2+ release, with cell Ca2+ decreasing progressively from 179 +/- 32 to 87 +/- 21 nM (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415738 TI - Inhibition of renin secretion from rat renal cortical slices by (R)-12-HETE. AB - The arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) inhibits renin secretion both in vivo and in vitro, but the enzymatic origin of the 12-HETE responsible for renin inhibition is unknown. These studies examined the effect of the 12-HETE stereoisomers (R)-12-HETE (a product of the cytochrome P-450 monooxygenase enzyme system) and (S)-12-HETE (a product of the lipoxygenase enzyme system) on basal and stimulated renin secretion from superficial cortical slices in the rat. First, rat cortex was shown to produce 12-HETE; chiral-phase high-performance liquid chromatography revealed that cortex produced 81% (S)-12 HETE and 19% (R)-12-HETE. (R)-12-HETE reduced basal renin release by 28 +/- 4% to 49 +/- 5% at concentrations of 10(-9) to 10(-7) M (P < 0.05 to 0.01). (S)-12-HETE did not significantly affect renin release. (R)-12-HETE also blunted isoproterenol-stimulated renin secretion (P < 0.05) at a concentration of 10(-6) M. 20-HETE, another cytochrome P-450 product, did not exert a significant effect on renin release. In summary, both (R)-12-HETE and (S)-12-HETE are synthesized by renal cortical tissue. Only (R)-12-HETE directly inhibits in vitro renin release. These findings suggest that the renal cytochrome P-450 enzyme system is capable of directly influencing local renin secretion. PMID- 1415739 TI - Fetal-maternal fluid and electrolyte relations during chronic fetal urine loss in sheep. AB - Our aim was to determine the effects of prolonged removal of fetal urine during late gestation on fetal-maternal fluid and electrolyte relationships. We measured the volume and composition of fetal urine and amniotic and allantoic fluids and the composition of fetal and maternal plasma in sheep before and during continuous urine drainage, which began at 130 days of gestation and continued until the onset of labor; a control group was also studied. The response to fetal urine drainage occurred in two phases. In the "acute" phase (1-3 days), amniotic and allantoic fluid volumes decreased significantly, presumably due to their reabsorption into the fetal chorionic circulation or swallowing of amniotic fluid by the fetus. During the "chronic" phase, starting 3-5 days after urine drainage, a significant reversal in the transplacental osmotic gradient occurred due to a decrease in maternal plasma osmolality. During the entire drainage period (14.1 +/- 1.1 days, mean +/- SE, n = 5) at least 542 ml/day of water and 24 mmol/day of electrolytes passed from the mother into the fetal circulation and fetal plasma osmolality was unchanged. We conclude that, despite the loss of substantial water and electrolytes, the fetus is able to maintain its growth and fluid and electrolyte homeostasis by obtaining water and electrolytes initially from the amniotic and allantoic fluids and subsequently from its mother. The movement of water and electrolytes to the fetus would have been facilitated by the reversed transplacental osmotic gradient. PMID- 1415740 TI - Identification and localization of renal Na(+)-Ca2+ exchanger by polymerase chain reaction. AB - The molecular identity of the renal Na(+)-Ca2+ exchanger was determined by a homology-based polymerase chain reaction (PCR) cloning strategy. Rat kidney RNA was amplified by PCR, using oligonucleotide primers based on regions of low degeneracy in the published canine cardiac Na(+)-Ca2+ exchanger cDNA sequence, and the products were subcloned and sequenced. A 452-bp clone (NCX1) was identified, which shares 89% nucleotide and 98% amino acid sequence identity with the canine cardiac exchanger, suggesting that they are products of the same gene. NCX1 was shown, by Northern analysis, to hybridize to an abundant major transcript of 7 kb and a minor one of approximately 14 kb both localized predominantly to kidney cortex. Microdissected tubule PCR analysis revealed that NCX1 was enriched in distal convoluted tubule compared with other cortical nephron segments. Such a location is consistent with a Na(+)-Ca2+ exchanger corresponding to NCX1 playing a major role in active Ca2+ reabsorption at this site. PMID- 1415741 TI - Altered synthesis of proteoglycans by cyst-derived cells from autosomal-dominant polycystic kidneys. AB - Normal human renal epithelial cells (NK) and cells from cysts of autosomal dominant polycystic kidneys (ADPKD) were radiolabeled with [35S]sulfate. A two- to three-fold decrease in the radioactivity incorporated into the proteoglycan (PG) fraction, as ascertained by tissue autoradiography and biochemical techniques, was observed in the ADPKD group. In subconfluent NK cells, PGs eluted as two peaks with different proportions of chondroitin sulfate (CS) and heparan sulfate (HS) in the cellular and media fractions. In the confluent stage, only a single major peak in the media and matrix fractions was seen and had variable proportions of CS and HS. In subconfluent ADPKD monolayers, cellular PGs eluted as two peaks, with the major peak of higher molecular weight compared with NK cells. In confluent stage, there was a single PG peak of a relatively higher molecular weight, with a variable increase in the proportions of CS vs. HS and lower charge-density characteristics. These findings indicate that size and species of PGs vary during subconfluent and confluent stages of culture and elucidate a defect in the biosynthesis of PGs in human ADPKD cells. PMID- 1415742 TI - Adriamycin nephropathy: a model to study effects of pregnancy on renal disease in rats. AB - The influence of pregnancy on the evolution of primary renal disease is still a matter of controversy. Hypertension and derangement of renal function may occur. The pathophysiology of these complications is poorly understood. In the present study, we assessed the influence of pregnancy on the evolution of adriamycin (Adr) nephropathy. Four groups of animals were studied: 1) control virgin rats (C), 2) normal pregnant rats (NP), 3) virgin rats with nephropathy (Adr), and 4) pregnant rats with nephropathy (Adr-P). Inulin clearance measured at the end of pregnancy in awake rats was similar in NP (1.68 +/- 0.20 ml/min) and C (1.39 +/- 0.03 ml/min). In Adr-P rats, it tended to decrease (1.22 +/- 0.7 vs. 1.93 +/- 0.44 ml/min in Adr rats). Mean arterial pressure was increased in Adr-P rats (137 +/- 2.5 vs. 95 +/- 3.2 mmHg in NP; P < 0.001). Urinary protein excretion was 216 +/- 61 mg/day in Adr-P compared with 28.7 +/- 18 mg/day in Adr (P < 0.001). A significant increase in the glomerular thromboxane B2-to-prostaglandin E2 ratio was found in Adr-P rats (1.15 +/- 0.26 vs. 0.52 +/- 0.12 in Adr rats; P < 0.03). In NP rats, no change was observed. Kidneys and placentas were normal on light and electron microscopy. Thus pregnant rats with adriamycin nephropathy developed a clinical picture with several features of preeclampsia. Changes in glomerular prostanoid synthesis might play a role in the development of this complication. PMID- 1415743 TI - Effect of changes in extracellular potassium on intracellular pH in principal cells of frog skin. AB - Intracellular pH (pHi), apical membrane potential (Va), and fractional apical membrane resistance (FRa) were measured in principal cells of isolated frog skin (Rana pipiens) with double-barreled microelectrodes under short-circuit and open circuit conditions. Basolateral exposure to high K+ concentration or Ba2+ depolarized V(a), decreased short-circuit current, and increased FRa and pHi. However, an increase in K+ subsequent to Ba2+ application did not induce additional changes in these parameters. High basolateral K+, previously shown to increase apical K+ secretion (N. S. Bricker, T. Biber, and H. H. Ussing. J. Clin. Invest. 41: 88-99, 1963), also increased apical Na+ conductance. The depolarization and intracellular alkalinization induced by high K+ were also observed in absence of Na+, Cl-, and HCO3- and in presence of 4,4' diisothiocyanostilbene-2,2'-disulfonic acid. Under all these conditions pHi moved toward electrochemical equilibrium. Reduced basolateral K+ hyperpolarized V(a) and decreased pHi. The data suggest that depolarization and hyperpolarization of the apical and/or basolateral membrane are associated with an increase and decrease, respectively, in pHi without involvement of Na(+)-H+, Cl(-)-HCO3-, or K(+)-H+ exchange and are apparently also independent of an active H+ secretion pathway. This indicates the presence of a potential-dependent H+ and/or OH- conductance in the apical and/or basolateral cell membrane that may play an important role in pHi regulation and signal transduction. PMID- 1415744 TI - Distribution and content of renin and renin mRNA in remnant kidney of adult rat. AB - To determine whether kidney hypertrophy secondary to reduction of renal mass affects the intrarenal distribution and concentration of renin mRNA and its protein, adult male Sprague-Dawley rats were studied 4 wk after sham operation (Sham, n = 10), uninephrectomy (UNX, n = 14), or five-sixths nephrectomy (5/6 NX, n = 12). Left kidney weight-to-body weight ratio (x10(3)) was higher in 5/6 NX (6.6 +/- 0.2) than in UNX (4.5 +/- 0.2) or Sham (3.8 +/- 0.1) groups (P < 0.001). The percentage of juxtaglomerular apparatuses (%JGA) containing renin was lower in 5/6 NX (32 +/- 5) than in UNX (56 +/- 2, P < 0.001) or Sham (50 +/- 1, P < 0.05) groups. Renal renin mRNA concentrations (pg renin mRNA/microgram total RNA) detected by radiodensitometric renin mRNA dot-blot assay were lower in 5/6 NX (1.8 +/- 0.3) than in UNX (13.2 +/- 1) or Sham (14.2 +/- 1.1, P < 0.001). In situ hybridization histochemistry demonstrated that in all groups of rats renin mRNA was confined to the JGA. However, the hybridization signals (grains/JGA) were less intense in 5/6 NX (211 +/- 24) than in UNX (486 +/- 35) or Sham (541 +/- 40) groups (P < 0.001). Renal renin concentration (ng angiotensin I.mg protein-1.h-1) tended to be lower in 5/6 NX (20 +/- 15) than in UNX (44 +/- 7.8) or Sham (60.8 +/- 10) groups. In addition, plasma renin activity (ng.ml-1.h-1) was lower in 5/6 NX (3.8 +/- 0.6) than in UNX (8.8 +/- 1.8, P < 0.05) or Sham (14.3 +/- 2, P < 0.001) groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415745 TI - Adaptation of rabbit cortical collecting duct to in vitro acid incubation. AB - Cortical collecting ducts (CCDs) isolated from acid-loaded rabbits and perfused in vitro absorb HCO3-, whereas CCDs from normal animals secrete HCO3-. We have previously shown that CCDs incubated in vitro for 3 h at pH 6.9 show a reduction in net (baseline and stimulated) HCO3- secretion. In this study we ascertained the minimum duration of an acidic stimulus necessary to induce adaptive changes in stimulated HCO3- secretion (determined in the absence of basolateral Cl-) and the roles of protein synthesis and cytoskeletal function in this process. CCDs incubated in acid (pH 6.8, HCO3- 6 mM) for 1 h followed by incubation at pH 7.4 (HCO3- 25 mM) for 2 h showed a 41% reduction in stimulated HCO3- secretion (P < 0.001), similar to that observed after 3 h of incubation at pH 6.8. However, this incubation protocol failed to enhance stimulated HCO3- absorption (determined in the absence of luminal Cl-). Addition of 10 microM anisomycin, a reversible inhibitor of protein synthesis, throughout the entire period of incubation (1 h at pH 6.8 plus 2 h at pH 7.4) blocked adaptive reduction in HCO3- secretion, as did exposure to anisomycin only during the initial 1 h of acid incubation. In contrast, anisomycin application during the 2-h incubation at pH 7.4 failed to block this adaptation of HCO3- secretion. Application of 4 microM actinomycin D, an inhibitor of DNA transcription, during the acid incubation also prevented the adaptive response, as did application during the total or during the 2-h pH 7.4 incubation period of 0.2 microM cytochalasin D, an inhibitor of actin filament function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415746 TI - Calculation of oxygen diffusion across the surface of isolated perfused hearts. AB - Although exact mathematical descriptions of oxygen diffusion into unperfused isolated organs are known, no analytic solution is available for perfused organs. Here, we derive an equation for oxygen diffusion across the epicardial surface of perfused hearts. Our oxygen transport model incorporates oxygen delivery from the capillary perfusate, oxygen consumption, diffusion among adjacent capillary exchange regions, and diffusion across the epicardial surface. The wall of the heart is modeled by a slab of tissue. The derived equation fits experimental data on the diffusive oxygen flux across the surface of isolated saline-perfused guinea pig hearts, obtained by measuring oxygen uptake from the perfusate at various oxygen tensions in the surroundings of the isolated heart. The model predicts that in isolated arrested guinea pig hearts suspended in air, 25% of the oxygen taken up from the saline perfusate (PO2 approximately 680 mmHg) diffuses out of the heart across the surface. In beating isolated guinea pig hearts, 5% of the oxygen taken up from the perfusate diffuses across the surface. PMID- 1415747 TI - Limited left ventricular inotropic response to exercise in early phase of pressure overload in dogs. AB - To study the mechanisms of myocardial adaptation to increased stress in the early phase of left ventricular (LV) pressure overload, 12 dogs were instrumented with LV micromanometer, LV dimensional ultrasonic crystals, aortic catheter, and aortic occluder cuff. After recovery, animals performed graded exercise with acute aortic stenosis (AS) or sustained (24 h) aortic stenosis (SS). At baseline, LV functional parameters with SS were not different from those obtained with AS. LV peak pressure increased similarly during exercise with AS or SS, but LV peak dP/dt was lower with SS than with AS (peak values, 6,292 +/- 525 vs. 7,570 +/- 432 mmHg/s; P < 0.05). LV end-diastolic pressure increased from 9.7 +/- 1.7 to 21.4 +/- 3.3 mmHg (P < 0.05) during exercise with SS, but was unchanged with AS. The decrease of the time constant of isovolumic pressure fall during exercise was significantly smaller after SS than during AS (P < 0.05). In addition, the percentage of subendocardial wall thickening did not increase during exercise with SS (30.3 +/- 3.6%), while it increased significantly with AS (from 29.3 +/- 3.3 to 39.4 +/- 4.5%; P < 0.01). Plasma catecholamine levels were similar at baseline and increased to similar levels during exercise with AS and SS. In the early phase of pressure overload, we conclude that exercise capacity is maintained but that the LV inotropic response to exercise is modified with an altered relaxation process and a lesser utilization of subendocardial inotropic reserve. PMID- 1415748 TI - Altered pressure-volume relation of right atrium and venoatrial junction in diabetic rats. AB - Previous studies have indicated a blunted volume reflex in diabetic rats. This alteration of the volume reflex may be due to differences in distensibility of the right atrium and venoatrial junction, which contain a large number of volume receptors. This study was designed to determine whether the distensibility of the right atrium and venoatrial junction is altered in the diabetic rat. The distensibility was assessed by measuring the stiffness constants [slope of pressure-volume (P-V) curve] of the right atrium and venoatrial junction in 2-wk streptozotocin-induced diabetic rats. The P-V data of the right atrium and venoatrial junction were measured in control and diabetic rats over a range of 0 10 mmHg by infusion of isotonic saline in KCl-arrested, in situ hearts. Similar P V data also were determined in an additional group of diabetic rats under daily insulin treatment, which normalized plasma glucose. The mean slope of the P-V curve of the right atrium and venoatrial junction in the diabetic rats was significantly greater than the mean slope of the control and insulin-treated diabetic rats. The results indicate that diabetic rats have stiffer right atria and venoatrial junctions, which may reduce stimulation of the volume receptors to acute volume loading. In addition, the increased stiffness in the diabetic rats was prevented by chronic insulin treatment. An altered afferent limb of the volume reflex in diabetic rats contributing to blunted diuretic and natriuretic responses to volume loading may be due to these documented changes in the distensibility of the right atrium and venoatrial junction. PMID- 1415749 TI - Long-term calorie restriction enhances baroreflex responsiveness in Fischer 344 rats. AB - Diet influences many aspects of cardiovascular function. Restriction of caloric intake represents a major nonpharmacological means of reducing blood pressure. The aim of the present work was to determine the effects of long-term calorie restriction on mean arterial pressure (MAP) and baroreflex responsiveness of the conscious, normotensive, nonobese Fischer 344 male rat. From 6 wk of age rats ate either ad libitum or 60% of the amount consumed by those eating ad libitum. Calorie restriction had no effect on MAP of rats 12-14 mo of age; the MAP for the ad libitum fed and calorie-restricted groups were 114.6 +/- 1.6 and 111.6 +/- 0.8 mmHg, respectively. Basal heart rate (HR), however, was reduced from 396 +/- 6 beats/min in the libitum-fed group to 333 +/- 5 beats/min in the calorie restricted group. Administration of sodium nitroprusside (SNP) (both as bolus and constant infusion) and phenylephrine (PE) (bolus alone) elicited tachycardia and bradycardia in both groups. The calorie-restricted group exhibited greater baroreflex responsiveness to hypotensive stress than did the ad libitum-fed group. For constant infusion of SNP, the baroreflex gain of the calorie restricted group (-5.43 +/- 0.56 beats.min-1.mmHg-1) was significantly greater than that of the ad libitum-fed group (-2.14 +/- 0.19 beats.min-1.mmHg-1). Bolus injections of SNP elicited similar results. Calorie restriction only minimally altered the baroreflex responsiveness to hypertensive stress elicited by bolus injections of PE, although the relationship between HR and MAP was shifted to the left in the calorie-restricted group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415750 TI - Spinal stimulation to locate preganglionic neurons controlling the kidney, spleen, or intestine. AB - The organization of sympathetic preganglionic neurons may be a substrate for selective control of sympathetic outflow to different vascular beds. This study was done to determine the spinal segments containing preganglionic neurons controlling discharge of renal, splenic, and mesenteric postganglionic nerves. In urethan-anesthetized rats, preganglionic neurons were stimulated by microinjecting D,L-homocysteic acid (3 nl, 0.17 M) into the lateral gray matter of the third thoracic (T3) to the fourth lumbar (L4) spinal segments. Responses from all three nerves could be elicited from segments T4-T13. The greatest increases in renal nerve discharge were evoked from segments T8-T12, the largest increase of 59 +/- 9% elicited from T10. Increases in splenic and mesenteric nerve discharge were smaller and were evoked more uniformly from T4-L3. The largest increases in discharge of splenic and mesenteric nerves were 19 +/- 5% (from T5) and 26 +/- 4% (from T10), respectively. The widely overlapping spinal cord segments controlling these three organs suggest that location of the preganglionic neurons in different spinal segments is not part of the mechanism for selective sympathetic control. However, the larger renal nerve responses demonstrate that sympathetic output to these organs can be differentiated at the level of the spinal cord. PMID- 1415751 TI - Neuropeptide Y and coronary vasoconstriction: role of thromboxane A2. AB - We previously reported that coronary constriction following neuropeptide Y (NPY) was alleviated by cyclooxygenase blockade. To determine the role of thromboxane A2 (TxA2), anesthetized dogs received two paired doses of NPY given 2 h apart. Nine control dogs received NPY alone. Nine test dogs received one of three TxA2 receptor antagonists given between the doses of NPY. Also, five dogs received NPY during which prostaglandins were measured. In controls, NPY decreased coronary blood flow and increased aortic pressure; coronary resistance was increased significantly. Heart rate fell, and myocardial oxygen consumption was unchanged. Thromboxane receptor blockers significantly relieved the coronary constrictor effect of NPY. The reduction in coronary blood flow was blunted, while heart rate, first derivative of left ventricular pressure, and myocardial oxygen consumption were unchanged. Alleviation by TxA2 receptor blockade paralleled that reported for cyclooxygenase inhibitors. Also, significant increases in coronary venous TxA2 were seen at the time of maximal increases in coronary resistance, while prostacyclin was unchanged. In summary, TxA2 appears to mediate part of the coronary constrictor effect of NPY. PMID- 1415752 TI - Cardiac adaptation of sarcomere dynamics to arterial load: a model of hypertrophy. AB - In the past, the dynamics of the left ventricle were studied by its response to altered venous and arterial load for a given heart. This led researchers to propose the concept of an arterioventricular match or optimal point of function. The model of this paper reverses that idea by fixing preload and afterload while computing cardiac function due to altered left ventricular size or shape, resulting from modification of the number of parallel and series sarcounits. A mathematical model of physiological hypertrophy is introduced. Series and parallel arrangements of sarcounits constitute a cylindrical model of the left ventricle. Filling occurs from a venous reservoir with constant pressure through a valve, while ejection takes place into a three-element model of the systemic arterial system through another valve. It is found that the dynamics of the myofibrils can be matched to those of the left ventricle by choosing a ventricular shape that results in a minimum in myocardial O2 consumption (MVO2) for any constant ventricular load. A unique solution for the size of the ventricle results if the rate of MVO2 is specified. The model is able to predict correctly hypertrophy due to hypoxia and due to pressure (concentric) and volume (eccentric) overloads. PMID- 1415753 TI - Transvascular albumin and IgG flux in skin after a continuous 3-h bradykinin infusion. AB - Bradykinin (1 microgram/min) was infused into the femoral artery of one hindleg of anesthetized rabbits for 3 h. Measurements of the initial extravascular uptake for labeled albumin and immunoglobulin (Ig) G were compared with measurements of the lymph protein flux for endogenous albumin and IgG. With bradykinin, the initial extravascular uptake for both albumin and IgG, calculated as the 1-h extravascular distribution space at plasma concentration divided by time and expressed as a plasma clearance, was 12 times the control values. For both proteins, the lymph fluxes were not significantly greater than the values for extravascular uptake, indicating that the sustained increase in lymph protein flux was not due to washout of interstitial protein. The extravascular uptake for IgG was approximately 80% of that for albumin in both control and bradykinin animals, suggesting that the sustained response did not change the selectivity between the two proteins. Changes in the extravascular masses of endogenous albumin and IgG suggest that the initial response to bradykinin was a transient formation of endothelial gaps that did not restrict transvascular IgG transport more than albumin. PMID- 1415754 TI - Endothelium-dependent ANF secretion in vitro. AB - Coculture of endothelial cells with atrial cells (R. A. Lew and A. J. Baertschi. Biochem. Biophys. Res. Commun. 163: 701-709, 1989) increased atrial natriuretic factor (ANF) release to 205 +/- 15% (n = 33 experiments) of basal secretion (2.02 +/- 0.33 ng/ml). Stimulation of ANF release by endothelial cells was significantly reduced (P < 0.05) by addition of the calcium channel antagonist nicardipine (Nic, 100 nM; by 69 +/- 4%), the guanylate cyclase activator sodium nitroprusside (SNP, 1 microM; by 97 +/- 27%), or acetylcholine (ACh, 10 microM; by 55 +/- 13%). Endothelial cell-conditioned medium elicited a 62 +/- 10% (n = 10) increase in ANF release. Rat and porcine endothelin (0.1-100 nM) each elicited a dose-dependent increase in ANF release [up to 84 +/- 14% (n = 18) over baseline]. The activity of conditioned medium was not affected by heat or trypsin treatment, but was significantly reduced by addition of Nic or SNP and was attenuated by ACh. Stimulation of ANF by 1 nM synthetic rat or porcine endothelin was also unaffected by heat or trypsin but was significantly reduced by Nic, SNP, and ACh. Addition of endothelin-specific antiserum abolished the ANF stimulatory activity of endothelial cell-conditioned medium. Neither inhibition of superoxide anion by superoxide dismutase nor inhibition of endothelium-derived nitric oxide production by NG-monomethyl-L-arginine affected the ANF release from coculture. Thus endothelial cells release a heat-stable, diffusible ANF stimulatory factor, which is not endothelium-derived relaxing factor or superoxide anion but is biologically and immunologically similar to endothelin. PMID- 1415755 TI - Sympathetic modulation of blood flow and O2 uptake in rhythmically contracting human forearm muscles. AB - This study tested the effects of sympathetically mediated changes in blood flow to active muscles on muscle O2 uptake (VO2) in humans. Four minutes of graded (15 80% of maximum voluntary contraction, MVC) rhythmic handgrip exercise were performed. Forearm blood flow (FBF) (plethysmography) and deep vein O2 saturation were measured each minute. Forearm O2 uptake was calculated using the Fick principle. In protocol 1, exercise was performed while supine and again while upright to augment sympathetic outflow to the active muscles. Standing reduced FBF at rest from 3.6 to 2.2 ml.100 ml-1.min-1 (P < 0.05). During light exercise (15-40% MVC) FBF was unaffected by body position. Standing reduced FBF (P < 0.05) from 36.0 to 25.2 ml.100 ml-1.min-1 and forearm VO2 from 38.2 to 28.1 ml.kg-1.min 1 during the final work load. In protocol 2, exercise was performed while supine before and after local anesthetic block of the sympathetic nerves to the forearm. Sympathetic block increased FBF at rest from 3.1 to 8.9 ml.100 ml-1.min-1 (P < 0.05), and FBF was higher during all work loads At 70-80% of MVC sympathetic block increased FBF from 35.4 to 50.7 ml.100 ml-1.min-1 (P < 0.05), and forearm VO2 from 45.5 to 54.2 ml.kg-1.min-1 (P < 0.05). These results suggest that in humans sympathetic nerves modulate blood flow to active muscles during light and heavy rhythmic exercise and that this restraint of flow can limit O2 uptake in muscles performing heavy rhythmic exercise. PMID- 1415756 TI - Baro- and ventricular reflexes in conscious dogs subjected to chronic tachycardia. AB - It has been well documented that the arterial baroreflex is depressed in chronic congestive heart failure. Furthermore, cardiopulmonary reflexes have also been shown to be depressed in heart failure. Because cardiac reflexes can be mediated by both mechanical and chemical stimuli, we undertook the current study to determine whether chemically activated cardiac reflexes (Bezold-Jarisch) are abnormally depressed in dogs with chronic heart failure at a point in time when arterial baroreflexes were clearly depressed. We studied heart rate and arterial pressure responses in 13 conscious instrumented dogs before and after chronic ventricular pacing at 250 beats/min for 4-5 wk. At the time the study was done each dog showed both hemodynamic and clinical signs of congestive heart failure. The arterial baroreflex was evaluated by analyzing the heart rate response to acute injections of phenylephrine and nitroglycerin. The Bezold-Jarisch reflex was assessed in nine dogs by determining the heart rate and blood pressure responses to intracoronary injections of various doses of veratridine. Arterial baroreflex responses were uniformly depressed following ventricular pacing. The phenylephrine slope was reduced by 55.8 +/- 6.9% (P < 0.001), and the nitroglycerin slope was reduced by 67.9 +/- 5.0% (P < 0.0001) in the heart failure state. Significant bradycardia and hypotension were seen at each dose of veratridine given (0.01, 0.1, and 0.4 microgram/kg). When compared with the prepaced control state, the magnitude of the hypotension was no different in the heart failure state in response to any dose of veratridine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415757 TI - Heterogeneous distribution of endothelium-dependent relaxations resistant to NG nitro-L-arginine in rats. AB - Endothelium-dependent relaxations that are resistant to inhibitors of nitric oxide synthase probably are mediated by endothelium-dependent hyperpolarization of the vascular smooth muscle. Experiments were performed to examine the distribution of this type of relaxation along the arterial tree of the rat by measuring changes in isometric force. Acetylcholine induced concentration- and endothelium-dependent relaxations in aortas and in pulmonary, common iliac, femoral, mesenteric, and renal arteries contracted with phenylephrine. In the presence of NG-nitro-L-arginine, the cumulative administration of acetylcholine induced relaxations only in the femoral, mesenteric, and renal arteries. The calcium ionophore A23187 relaxed mesenteric arteries contracted with phenylephrine in a concentration- and endothelium-dependent manner. The concentration-relaxation curve to A23187 was shifted to the right in the presence of NG-nitro-L-arginine. The maximal relaxations induced by lemakalim, a K+ channel opener, were smaller in those arteries that did not exhibit NG-nitro-L arginine-resistant relaxations. These results suggest that NG-nitro-L-arginine resistant relaxations are more frequently observed in smaller arteries. The arteries that exhibit NG-nitro-L-arginine-resistant relaxations may be more sensitive to an endothelium-derived substance that causes hyperpolarization of vascular smooth muscle cells. PMID- 1415758 TI - Correlation of structure and viscoelastic properties in the pericardia of four mammalian species. AB - Although the pericardium is recognized as having important contributions to ventricular function, the relationship between its functional role and structural composition remains poorly understood. Conflicting evidence from low strain rate experiments has shown that differences exist between the mechanical properties of canine, human, and bovine pericardium but with no structural explanation for these differences. This paper examines the pericardia of calves, dogs, pigs, and sheep using a structural/mechanical approach with techniques novel to the pericardial literature. High strain rate mechanical testing for stress-strain response, stress relaxation, and forced vibration response has shown the pericardium to be much more viscoelastic than previously believed under large deformations, but to be quite elastic in small vibrations. The thinner canine and porcine pericardia were found to be significantly stiffer than the thicker bovine and ovine tissues, but equivalently viscoelastic. Biochemical analysis shows these thinner tissues to have significantly higher levels of type III collagen combined with a higher degree of cross-linking. This is the first structural explanation for differences in mechanical properties between the pericardia of different species. PMID- 1415759 TI - Ischemic preconditioning protects against infarction in rat heart. AB - We examined the anti-infarct effect of ischemic preconditioning in the rat heart. All hearts were subjected to 30 min of regional coronary ischemia and 2 h of reperfusion. Infarct size was determined by tetrazolium. The control group had an average infarct size of 31% of the risk zone. Three 5-min cycles of preconditioning ischemia limited the infarct size to 3.7%. Neither the adenosine receptor blocker PD 115,199 nor the ATP-sensitive potassium channel blocker, glibenclamide, could block this protection. Intracoronary adenosine A1-receptor agonist 2-chloro-N6-cyclopentyladenosine offered a significant anti-infarct protection to the isolated rat heart, however. Although one 5-min cycle of preconditioning did not protect the rat heart from infarction (31% infarction in risk zone), it did attenuate arrhythmias. We conclude that 1) the rat heart can be preconditioned, which argues against mitochondrial adenosinetriphosphatase being the mechanism of preconditioning; 2) the threshold for preconditioning is higher in rat than rabbit or dog; 3) a role for adenosine in preconditioning was only partially supported; and 4) a role for ATP-sensitive potassium channels was not supported. PMID- 1415760 TI - Role of adenosine for reactive hyperemia in normal and stunned porcine myocardium. AB - The role of adenosine for reactive hyperemia in normal and stunned myocardium was examined in 16 open-chest barbiturate-anesthetized pigs. Interstitial adenosine concentration was reduced or enhanced by intracoronary infusion of adenosine deaminase or the nucleoside transport inhibitor R 75231, respectively. In normal myocardium, adenosine deaminase reduced volume of hyperemia (Doppler flowmetry) after a 30-s left anterior descending coronary artery (LAD) occlusion by 20% (6 34%; P < 0.05), whereas R 75231 increased volume of hyperemia by 15% (2-24%; P < 0.05). Adenosine deaminase reduced volume of hyperemia after a 2-min LAD occlusion by 27% (13-37%; P < 0.001), whereas R 75231 increased volume of hyperemia by 66% (53-159%; P < 0.001). Adenosine deaminase and R 75231 did not affect maximal hyperemia. Volume of hyperemia after a 2-min LAD occlusion was reduced in stunned myocardium (%systolic segment length shortening reduced by approximately 45%, ultrasonic technique) but not further altered by either adenosine deaminase or R 75231. These findings show that adenosine contributes to reactive hyperemia after 30-120 s of ischemia in normal myocardium and indicate that the reduced reactive hyperemia in stunned myocardium is due to reduced accumulation of adenosine during ischemia. PMID- 1415761 TI - Electroporation and recovery of cardiac cell membrane with rectangular voltage pulses. AB - Electroporation of the cardiac cell membrane may result from intense electric fields applied to cardiac muscle, associated for example with defibrillation and cardioversion. We analyzed the distribution of voltage levels sufficient to cause electroporation in enzymatically isolated frog cardiac cells, using the cell attached patch-clamp technique with rectangular pulses similar to those used in experimental studies of cardiac defibrillation. Five-millisecond monophasic or ten-millisecond biphasic symmetric (1/1) and asymmetric (1/0.5) rectangular pulses of either polarity were applied to the cell membrane in 100-mV steps from 0.2 to 0.8 V. The membrane conductance was continuously monitored by a low voltage pulse train. In a total of 77 cells, we observed a step increase in conductance, occurring in 21% of cells at a transmembrane potential of 0.3 V, 52% at 0.4 V, 14% at 0.5 V, and 13% at 0.6-0.8 V. Electroporation occurred with this voltage distribution regardless of pulse shape, polarity, or the presence of all of the following ionic channel blockers: tetrodotoxin, barium, tetraethylammonium, 4-aminopyridine, cadmium, nickel, and gadolinium. The time course of membrane recovery was highly variable. The maintenance of a high membrane conductance after the shock pulse was associated with irreversible cell contracture provided that Ca2+ was included in the patch-pipette solution. However, with biphasic asymmetric pulses, the conductance recovered very quickly (< or = 37 ms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415762 TI - Left ventricular hypertrophy due to volume overload versus pressure overload. AB - Left ventricular hemodynamic overload produces an increase in stroke work (SW), which is compensated by the development of left ventricular hypertrophy. However, recent reports question the adequacy of this compensation in mitral regurgitation (MR). Accordingly, we examined the adequacy of compensatory hypertrophy in chronic experimental MR. Six dogs with chronic severe MR were matched according to SW with six dogs that had severe chronic aortic stenosis (ASSW). SW in the two groups was increased identically (40%) compared with normals. However, the hypertrophic response was much greater in the AS group [left ventricular wt (g) to body wt (kg) ratio (LVBW) 4.0 +/- 0.2 normals, 5.0 +/- 0.2 MR, and 7.5 +/- 0.2 ASSW; P < 0.05 MR vs. ASSW]. This differing hypertrophic response increased normalized SW, the area within the stress-volume loop, in MR (90 +/- 5 g) vs. 63 +/- 5 g in ASSW (P < 0.05). Thus in MR, each unit of myocardium had to perform more work than in AS. In a separate comparison, four different dogs with AS (ASHy), which had a similar amount of hypertrophy to the MR dogs (LVBW) (5.0 +/- 0.2 MR, 5.2 +/- 0.2 ASHy) were studied. SW was greater in the MR group, suggesting more SW overload was required to produce similar amounts of hypertrophy in MR vs. AS. Contractile function was depressed in the MR group but not in the AS. These findings indicate that the hypertrophic response to a similar SW demand is less in MR than AS, a response associated with contractile dysfunction in the MR group. PMID- 1415763 TI - Distribution of coronary collateral blood flow at different levels of collateral growth in conscious ponies. AB - Coronary collateral growth was stimulated in chronically instrumented conscious ponies by a previously validated intermittent coronary occlusion method. Changes in regional myocardial function (sonomicrometry) and reactive hyperemia (Doppler method) were used to monitor collateral growth and to program measurements of regional myocardial blood flow (microsphere method). A serial analysis of the transmural and lateral distributions of collateral blood flow was performed at the native and three superimposed levels of collateral growth. Results in nine animals undergoing an average of 553 +/- 188 brief coronary occlusions over 68 +/ 18 days demonstrated that as collateral conductance increased, the perfusion field within the ischemic region increased from the epicardium to the endocardium but not from the lateral edges to the center of the ischemic region. The findings are consistent with an analog model consisting of interarterial collaterals whose collective resistance is in series with arteriolar resistance of the recipient artery. No special protection of deeper myocardial layers by a subendocardial plexus or intramural collaterals was noted. Instead, the findings suggest that coronary extravascular compressive forces play a more important role than the transmural location of collaterals in determining the volume and spatial distribution of collateral blood flow during collateral growth in the pony. PMID- 1415764 TI - Sodium modulates inotropic response to hyperosmolarity in isolated working rat heart. AB - The present study was designed to examine the effects of acute changes in perfusate Na+ concentrations and osmolarities on left ventricular (LV) mechanics in the isolated working rat heart model. Specifically, we separated the effect of isosmotic perfusates with different Na+ concentrations on LV mechanics. After a control period during which the hearts were perfused in a working mode with a control solution of Krebs-Henseleit bicarbonate buffer (Na+ of 136 meq/l, Ca2+ of 2.6 mM, and osmolarity of 300 mosM), the hearts were subjected to different perfusates (Na+ of 96-156 meq/l and osmolarity of 240-380 mosM, using different mannitol concentrations) in a semirandom order. Peak LV pressure (PLVP), maximal time derivative of LV pressure (dP/dtmax), and cardiac output (CO) were recorded. Increasing Na+ concentrations from 96 to 156 meq/l, using isosmotic perfusates, decreased PLVP, dP/dtmax, and CO in a dose-dependent manner. The dose-dependent behavior was evident for tonicities of 240, 280, 320, and 360 but not for 380 mosM. Increasing Na+ concentration from 96 to 136 meq/l at constant perfusate tonicity (320 mosM) decreased dP/dtmax from 6,753 +/- 133 to 5,602 +/- 418 mmHg/s (P < 0.001). Rearranging the same results to examine the effect of perfusate tonicity with iso-Na+ concentration demonstrated that increasing perfusate osmolarity had a dose-dependent effect on PLVP, dP/dtmax, and CO. At a constant Na+ concentration of 116 meq/l, increasing perfusate osmolarity from 240 to 320 mosM increased dP/dtmax from 6,116 +/- 132 to 7,274 +/- 594 mmHg/s (P < 0.01). Further increase in perfusate tonicity to 380 mosM decreased dP/dtmax to 2,338 +/ 398 mmHg/s (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415765 TI - Sodium-calcium exchange-mediated contractions in feline ventricular myocytes. AB - The hypothesis that Ca entry by the sarcolemmal Na-Ca exchange mechanism induces sarcoplasmic reticulum (SR) Ca release, loads the SR with Ca, and/or directly induces contractions by elevating cytosolic free Ca was tested in voltage-clamped feline ventricular myocytes. Intracellular Na concentration was increased by cellular dialysis to enhance Ca influx via "reverse-mode" Na-Ca exchange at positive membrane potentials, at which the "L-type" Ca current (ICa) should be small. Contractions were induced in the presence of Ca channel antagonists by depolarization to these potentials, suggesting that Ca influx via reverse-mode Na Ca exchange was involved. These contractions had both phasic (SR related) and tonic components of shortening. They were smaller and began with more delay after depolarization than contractions which involved ICa. The magnitude of shortening was graded by the amount and duration of depolarization, suggesting that Ca influx via reverse-mode Na-Ca exchange has the capacity to induce and grade SR Ca release. Small slow contractions could be evoked in the presence of ryanodine (to impair SR function) and verapamil (to block ICa), supporting the idea that Ca influx via Na-Ca exchange is sufficient to directly activate the contractile proteins. Contractions induced by voltage steps to +10 mV, which were usually small when ICa was blocked, were potentiated if preceded by a voltage step to strongly positive potentials. This potentiation was inhibited by ryanodine, suggesting that Ca entry that occurs by Na-Ca exchange may be important for normal SR Ca loading.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415766 TI - Tissue uptake of insulin and inulin in red and white skeletal muscle in vivo. AB - By employing a tissue uptake technique, the kinetics of the plasma-interstitial equilibration of radiolabeled insulin, inulin, and albumin were followed in four muscles of differing capillarity in anesthetized rats. The soleus muscle (SOL), and the red portion of the gastrocnemius muscle (RG), as well as the extensor digitorum longus muscle (EDL) and the white portion of the gastrocnemius muscle (WG) were investigated. After constant intravenous tracer infusions and repeated plasma sampling under euglycemic clamp conditions, animals were killed at varying time intervals and the muscles mentioned above were dissected out. The radioactivity of tracer per gram of tissue in each muscle divided by the plasma activity of tracer per milliliter of plasma, i.e., "the plasma equivalent space" of tracer, thus could be followed as a function of time. From this function the permeability-surface area (PS) of inulin as well as the distribution volumes at time 0 (V0) of inulin and insulin and their equilibrium distribution volumes (VE) were assessed. The PS for inulin (in ml.min-1.100 g muscle-1) was 0.52 +/- 0.10 (mean +/- SE) in WG, increasing with more red fibers to 1.37 +/- 0.18 in SOL. Also the inulin interstitial distribution volume (at blood-tissue tracer equilibrium; VE) increased in this order (in ml/100 g) from 7.30 +/- 0.91 in WG to 12.93 +/- 0.89 in SOL. The V0 for insulin was found to be approximately fivefold larger than the plasma volume in each muscle sample, indicating a high degree of binding of insulin to structures within the vascular compartment, conceivably to the vascular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415767 TI - Role of myogenic response in enhancing autoregulation of flow during sympathetic nerve stimulation. AB - The effect of sustained sympathetic nerve stimulation on autoregulation of blood flow was examined in the exteriorized cat sartorius muscle using intravital microscopy. Without sympathetic nerve stimulation (SNS), second-order arterioles showed insignificant dilation (3%) during arterial pressure reduction from 110 to 60 mmHg; volume flow fell coincident with pressure reduction. During SNS, these arterioles constricted significantly (25%), and their dilation during pressure reduction (20%) was significant and was significantly greater than that without SNS. Volume flow increased significantly (20-60%) during pressure reduction, a phenomenon termed superregulation of flow. Elevation of ambient oxygen in the suffusate from 0 to 20% caused arteriolar constriction but did not abolish arteriolar dilation during pressure reduction under sustained SNS. Arteriolar response to venous pressure elevation was also affected significantly by sustained SNS. Without SNS, third-order arterioles showed slight dilation (4%) when femoral venous pressure was elevated by 10 mmHg. During SNS, these arterioles constricted significantly and constricted further (20%) when venous pressure was elevated. Using a local anesthetic (lidocaine), we determined that a local venous-arteriolar reflex was not involved in the arteriolar constriction. Our data suggest that superregulation of flow during sustained sympathetic nerve stimulation is not due to metabolic factors but rather to an enhanced myogenic response. PMID- 1415768 TI - Dobutamine improves afterload-induced deterioration of mechanical efficiency toward maximal. AB - We studied the effect of increased afterload on the ratios of O2 consumption (VO2) to external work (EW), VO2 to the systolic pressure-volume area (PVA), and PVA to EW at control state and with dobutamine in the left ventricles of open chest dogs. Left ventricular volume was measured with a volumetric conductance catheter and coronary flow with an electromagnetic flowmeter. Hexamethonium bromide and atropine sulfate were administered before changes in end-systolic pressure (Pes) with an infusion of nitroprusside or angiotensin II. Dobutamine enhanced ventricular end-systolic elastance by 100%. In the control, with increases in Pes, EW/VO2 remained unchanged, PVA/VO2 increased by 48%, and EW/PVA decreased by 26%. Dobutamine increased both EW/VO2 and EW/PVA at any given Pes but decreased PVA/VO2. During dobutamine, EW/VO2 increased significantly with increases in Pes. The ratio of measured EW/VO2 to the theoretically predicted maximal EW/VO2 value for a given end-diastolic volume and contractility was 0.83 at a Pes of 70 mmHg, and this ratio decreased by 33% with increases in Pes in the control. During dobutamine, measured EW/VO2 values were almost equal to each corresponding theoretical maximal value, and the average decrease in the ratio with increases in Pes was 7%. Thus the enhanced inotropic state by dobutamine can restore the afterload-induced deterioration of EW/VO2 toward the normal maximal level. PMID- 1415769 TI - Muscarinic cholinergic receptors in canine adrenal gland. AB - Muscarinic cholinergic receptor stimulation has been reported to modulate adrenal catecholamine and steroid secretion and influence medullary vascular tone. The present study was undertaken to localize and characterize muscarinic cholinergic receptor binding sites in canine adrenal medulla and cortex. Binding studies using semipurified membranes demonstrated specific, saturable binding of L [benzilic-4,4'-3H(N)]-quinuclidinyl benzilate ([3H]QNB) in medulla, with a dissociation constant (KD) equal to 152 pM and estimated maximal binding sites (Bmax) equal to 179 fmol/mg protein. Displacement of [3H]QNB by cholinergic agents in order of decreasing potency was atropine, pirenzepine, oxotremorine, pilocarpine, and carbamylcholine, suggesting the receptor was M1 subtype, similar to sympathetic ganglion muscarinic receptors. Autoradiographic imaging studies demonstrated highly specific, homogeneous binding throughout the medulla. No specific binding was found in adrenal cortex. These results suggest that muscarinic effects on blood flow may be neurally mediated, rather than the result of stimulation of vascular muscarinic receptors. In medulla, muscarinic receptors are evenly distributed and modulate catecholamine secretion in all cells rather than subpopulations of cells as in other species. Absence of [3H]QNB binding in cortex argues against muscarinic receptor modulation of cortical steroid secretion. PMID- 1415770 TI - Endotoxin enhances arachidonic acid metabolism by cultured rabbit microvascular endothelial cells. AB - This study demonstrates that bacterial lipopolysaccharide and lipid A exert a significant effect on eicosanoid formation by primary cultures of microvascular endothelial cells (MECs). Qualitative studies using [14C]-arachidonic acid demonstrated that prostaglandin E2 was the primary eicosanoid formed by MECs after 20 h of treatment with either vehicle or lipopolysaccharide. Significant, dose-dependent productions of PGE2 and prostacyclin, beginning at an endotoxin dose of 0.01 ng/ml, were quantified by radioimmunoassay in supernatants of cells treated for 20 h with lipopolysaccharide or lipid A. This eicosanoid production was inhibited by meclofenamate and cycloheximide and occurred without cellular injury. The time course and kinetics of eicosanoid production in response to endotoxin demonstrate a significant, time-related enhancement. Endotoxin-treated MECs responded to exogenous substrate with augmented PGE2 production, suggesting enhanced prostaglandin endoperoxide synthase activity. These results demonstrate a significant interaction of endotoxin with endothelial cells of microvascular origin that results in an enhanced potential for eicosanoid metabolism. This effect may be mediated in part through induction of prostaglandin endoperoxide synthase. PMID- 1415771 TI - Interstitial exclusion of albumin in rat tissues measured by a continuous infusion method. AB - Steady-state 125I-labeled rat serum albumin (125I-labeled RSA) concentration in plasma was maintained by intravenous infusion of tracer for 72-168 h with an implanted osmotic pump. At the end of the infusion period, the rat was anesthetized and nephrectomized, and extracellular fluid was equilibrated with intravenous 51Cr-labeled EDTA for 4 h. Five minutes before final plasma and tissue sampling, 131I-labeled bovine serum albumin (131I-labeled BSA) was injected intravenously as a plasma volume marker. Samples of skin, muscle, tendon, and intestine were assayed for all three tracers. Apparent distribution volumes were calculated as tissue tracer content/plasma tracer concentration. Interstitial fluid volume (Vi) was calculated as V51Cr-EDTA-V131I-BSA. Steady state extravascular distribution of 125I-labeled RSA as plasma equivalent volume (Va,p) was calculated as V125I-RSA-V131I-BSA. Steady-state interstitial fluid concentrations of 125I-labeled RSA in skin, muscles, and tendon were measured with nylon wicks implanted postmortem, and steady-state interstitial albumin distribution volumes were recalculated as wick-fluid equivalent volumes (Va,w). Relative albumin exclusion fraction (Ve/Vi) was calculated as 1-Va,w/Vi. For skin and muscle, steady-state 125I-labeled RSA tissue concentrations were reached at 72 h. Ve/Vi for albumin averaged 26% in hindlimb muscle, 41% in hindlimb skin, 30% in back skin, 39% in tail skin, and 54% in tail tendon. For muscle, Ve/Vi corresponds to expectation if all tissue collagen and hyaluronan is dispersed in the interstitium. However, for skin and tendon, albumin exclusion is considerably lower than expected on this basis, suggesting that much of their collagen is organized into dense bundles of fibers containing no fluid accessible to 51Cr labeled EDTA or 125I-labeled RSA. PMID- 1415772 TI - PEG-SOD improves postischemic functional recovery and antioxidant status in blood perfused rabbit hearts. AB - The isolated blood-perfused rabbit heart, subjected to 60 min of cardioplegic arrest and 60 min of reperfusion, was used to assess the effects of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) on postischemic recovery of left ventricular developed pressure (LVDP), the tissue activity of SOD, and tissue redox state. The five groups studied were the following: PEG-SOD-free control (group A), PEG-SOD as a pretreatment and as an additive during cardioplegia and reperfusion (group B), PEG-SOD as a pretreatment and a cardioplegic additive (group C), PEG-SOD in cardioplegia alone (group D), and PEG-SOD in reperfusion alone (group E). The results show that pretreatment with PEG-SOD improves postischemic recovery of LVDP (72 +/- 2% and 66 +/- 7 vs. 47 +/- 4% in groups B, C, and A, respectively). This protection was associated with an improved tissue redox state. Thus the ischemia-induced rise in oxidized glutathione was reduced from 313 +/- 26% (group A) to 162 +/- 15 and 138 +/- 14% (groups B and C, respectively), and the fall in reduced glutathione was attenuated from 51 +/- 5% to 35 +/- 6 and 13 +/- 5%, respectively. Tissue Mn-SOD activity was also conserved from 36 +/- 4% (group A) to 71 +/- 6 and 94 +/- 4% (groups B and C, respectively). No significant effect was seen when PEG-SOD was applied in cardioplegia or during reperfusion alone. PMID- 1415773 TI - Different responses of extent and velocity of contraction to dobutamine in conscious sheep. AB - The shortening- and shortening rate-preload-afterload relations, based on the concept of the myocardial end-systolic stress-strain relation (ESSSR), are a newly developed load- and size-independent assessment of myocardial contractility. The purpose of this study was to apply this assessment to compare extent and velocity of myocardial contraction during graded infusions of dobutamine. Seven chronically instrumented unsedated sheep were studied at rest and during graded infusions of dobutamine (2.5-20 micrograms.kg-1.min-1). The ESSSR were linear over a wide range of load alterations, whereas the end-systolic pressure-diameter relations (ESPDR) were generally nonlinear. Midwall shortening rate (SRm) at common preload and afterload representing contraction extent increased with each dose of dobutamine through 20 micrograms.kg-1.min-1. In contrast, midwall shortening (Sm) increased through dobutamine 5 micrograms.kg 1.min-1 but not at higher dobutamine infusion rates. Conventional endocardial shortening and the slope of the ESPDR, fitted to a linear model, exhibited responses similar to Sm. The velocity of circumferential endocardial fiber shortening (Vcf,c), Vcf,c-afterload relation, and maximum first derivative of left ventricular pressure exhibited responses similar to SRm. Thus both the extent and velocity of contraction increased at low doses of dobutamine, whereas only the velocity increased at high doses. Potential mechanisms for the saturated response of the extent of contraction include 1) shorter systolic time for contraction due to earlier onset of relaxation and 2) the utilization of myocardial contractile energy for left ventricular wall deformation at small cavity volumes at high doses of dobutamine. PMID- 1415774 TI - Biphasic blood volume changes with lower body suction in humans. AB - We recorded blood and plasma mass density and hematocrit of antecubital venous blood in 12 subjects in the supine position before, during, and after 20-40 min of lower body subatmospheric pressure (LBNP) of -35 mmHg. Mass density values decreased during the first minutes of LBNP, indicating a transient 2.8% blood volume gain before they rose as expected. After LBNP, a pronounced further density increase, indicating a further 1.5% hemoconcentration, preceded the return toward control. This pattern suggests reflex-driven transient filtration effects. Computed mass density of fluid exchanged between blood and extravascular space was 1,007.2 +/- 4.4 milligrams (37.0 degrees C); mass density of erythrocytes remained unaltered. We conclude that sudden unloading of central pressure receptors with LBNP causes microvascular fluid gain preceding fluid loss (hemoconcentration) during LBNP, and receptor loading after LBNP additionally causes fluid loss preceding inward filtration (hemodilution) during recovery. These effects can be quantified with high-precision blood and plasma mass densitometry performed by the mechanical oscillator technique. PMID- 1415775 TI - Regional cerebrovascular responses to progressive hypotension after traumatic brain injury in cats. AB - We investigated the effects of hypotension on cerebral blood flow (CBF) after traumatic brain injury (TBI) in cats. Isoflurane-anesthetized cats were prepared for TBI and for microsphere measurements of total (T) and regional (r) CBF. Four groups were studied: sham injury (group I, n = 6); TBI (group II, n = 6); isoflurane anesthesia, no TBI or hypotension (group III, n = 4); and isoflurane and TBI, no hypotension (group IV, n = 8). After TBI or sham trauma, mean arterial pressure (MAP) was reduced to 80, 60, and 40 mmHg by hemorrhage. Group I TCBF did not change significantly from baseline until MAP reached 40 mmHg, but rCBF was more dependent on MAP in anterior hemispheric than in brain stem regions. Group II TCBF was significantly lower than baseline, and group I TCBF at all levels of hypotension and autoregulation was impaired at higher MAP levels in anterior than in posterior brain regions. Groups III and IV indicated that decreases in TCBF were not due to duration of the preparation or to TBI in the absence of hemorrhagic hypotension. We conclude that global and regional autoregulation are absent in response to hemorrhagic hypotension after TBI. PMID- 1415776 TI - Effect of anesthetic on sympathetic responses evoked from cerebellar uvula in decerebrate cats. AB - The sympathetic mechanisms involved in the conversion of the tachycardia-pressor response evoked by electrical stimulation of the uvula (lobule IX of the posterior cerebellar cortex) in the unanesthetized decerebrate cat to a bradycardia-depressor response in the same, but anesthetized preparation, were investigated. Sympathoexcitation was produced in the inferior cardiac and renal sympathetic nerves in response to short train stimulation (2-5 pulses, 100-500 Hz) of the uvula in the unanesthetized decerebrate cat, and when paired stimuli (conditioning and test) were applied, the test-evoked potential in both nerves was similar to the response elicited by the conditioning stimulus. Anesthetic administered to these same animals caused the test response in both sympathetic nerves to be greatly decreased, yet the conditioning response was unchanged. The attenuation of the test response by the conditioning stimulus diminished during recovery from anesthesia. The recovery of the test response paralleled the time course of the return of the tachycardia-pressor effect evoked by long train stimulation of the uvula. It appears that anesthesia does not block the sympathoexcitatory response but acts to augment sympathoinhibitory processes associated with uvula stimulation; some possible mechanisms are discussed. PMID- 1415777 TI - Beneficial influence of vasoactive intestinal peptide on ventriculovascular coupling in closed-chest dogs. AB - The effect of vasoactive intestinal peptide (VIP) on ventriculovascular coupling in the intact cardiovascular system has not been defined. We studied seven dogs chronically instrumented with left ventricular (LV) pressure manometers and three sets of diameter gauges before and after infusions of 0.02, 0.05, and 0.10 microgram.kg-1.min-1 VIP. The dogs were studied after autonomic blockade, anesthesia, and intubation, with a fixed heart rate of 160 beats/min. Contractility was assessed using LV elastance at end systole (Ees) and the slope of the stroke work-end-diastolic volume relation. The vascular influence of VIP was quantified by determining effective arterial elastance (Ea) under steady state conditions. The overall effect on ventriculovascular coupling was assessed using the transfer of mechanical energy from LV to the arterial system (TransPVA) quantified as the percentage of pressure-volume area (PVA) expressed as stroke work. LV relaxation was measured using the time constant of LV pressure decay. The results showed that VIP increased contractility (Ees increased to 129, 156, and 181% of control; P < 0.01 for all vs. control) and decreased effective arterial elastance (Ea fell to 84, 68, and 64% of control; P < 0.0155 vs. control for the two higher doses). VIP had no consistent effects on LV relaxation. Thus, in addition to its positive ventricular effects (increased contractility), VIP has beneficial vascular effects (reduced Ea). These properties combine to improve ventriculovascular coupling, such that VIP enhances delivery of mechanical energy from the LV to the circulatory bed. PMID- 1415779 TI - A new approach to analysis of synchronized sympathetic nerve activity. AB - Renal sympathetic nerve activity (RSNA) recorded from the multifiber preparation is a continuously fluctuating variable in terms of period and amplitude, reflecting a coordinated tonic level of output from the vasomotor center. Yet current methods of analysis cannot simultaneously measure both of these parameters. A new accurate technique for assessing changes in global sympathetic activity is required. We made a novel application of a computerized peak detection algorithm (Cluster program) to recordings of synchronized sympathetic nerve discharges. The procedure was applied to this new area to retrieve information about the characteristics of synchronized RSNA. Peaks in synchronized RSNA activity were detected from short-term (20 ms) integrated recordings in which voltage changes had been digitized at 200 Hz and stored on computer. The program scanned the data series for significant increases followed by significant decreases in a small cluster of voltage values. The program permits the input of the cluster sample sizes for the test peaks and pre- and postpeak nadirs and also the minimum height to be defined as a peak. Once each synchronized RSNA peak had been detected, its corresponding amplitude, width, and peak-to-peak interval were calculated. The program successfully characterized RSNA in a group of eight cats and yielded results comparable to other analysis techniques. The peak-to-peak interval period showed two modes of synchronized discharge, one related to the cardiac cycle and a faster 8- to 14-Hz frequency. The synchronized peak amplitude and width showed unimodal frequency distributions. The relationship between each of the three variables was examined; only the peak height and width were significantly related to each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415778 TI - Effect of acute ventricular dilatation on fibrillation thresholds in the isolated rabbit heart. AB - We examined the effects of ventricular dilatation on epicardial refractoriness and ventricular fibrillation threshold (VFT) in the isolated, retrograde-perfused rabbit heart. Ventricular size was modified by acutely changing the volume of a fluid-filled balloon secured within either the left or right ventricle. Left ventricular dilatation (to an end-diastolic pressure of 30-38 mmHg) significantly decreased left ventricular effective refractory period (ERP) and myocardial wavelength (calculated as ERP x conduction velocity). Left VFT (determined by scanning the vulnerable period with a train of pulses) decreased from 6.4 +/- 0.9 to 4.4 +/- 0.5 mA; P < 0.01) with left but not right ventricular dilatation. Right ventricular dilatation was associated with a decrease in the right ventricular ERP and myocardial wavelength, and right VFT decreased from 13.6 +/- 1.8 to 4.1 +/- 0.3 mA (P < 0.01). Changes in VFT correlated with the decrease in local refractoriness and shortening of local excitation wavelength. PMID- 1415780 TI - Effect of adenosine deaminase on cardiac interstitial adenosine. AB - Adenosine deaminase was infused into isolated perfused guinea pig hearts to determine its effect on myocardial adenosine levels. The enzyme was administered during constant coronary flow perfusion at 6.11 +/- 0.36 ml.min-1.g-1. Venous adenosine was measured in samples of pulmonary artery effluent; epicardial and endocardial adenosine were measured with the porous nylon disk technique. Infusion of adenosine deaminase at 2.4 and 4.8 U/ml produced adenosine deaminase activity of 0.92 +/- 0.09 and 2.33 +/- 0.15 U/ml, respectively, in epicardial fluid and 1.93 +/- 0.28 and 4.84 +/- 0.47 U/ml, respectively, in endocardial fluid. Aortic pressure was unchanged by infusion of adenosine deaminase at both infusion rates. Adenosine deaminase (data from both infusion rates pooled) reduced epicardial adenosine from 0.327 +/- 0.028 to 0.139 +/- 0.022 microM, endocardial adenosine from 4.61 +/- 0.42 to 1.64 +/- 0.20 microM, and venous adenosine from 0.017 +/- 0.02 to 0.003 +/- 0.001 microM. The data indicate that infused adenosine deaminase reaches the epicardial and endocardial interstitial fluid (ISF) compartments. The absence of any effect on coronary pressure suggests that adenosine may not be involved in resting basal coronary tone. The presence of significant residual adenosine despite adenosine deaminase infusion indicates that adenosine production in the unstressed isolated guinea pig heart exceeds the degradative capacity of infused adenosine deaminase. Previous studies in which it was assumed that almost all of the endogenous adenosine is inactivated by the infusion of adenosine deaminase should be reevaluated in light of these observations. PMID- 1415781 TI - Maximal myocardial blood flow is enhanced by chronic hypoxemia in late gestation fetal sheep. AB - The measurement of maximal myocardial blood flow gives information about the total cross-sectional area of the coronary resistance vessels. During a continuous left atrial infusion of adenosine (60 micrograms.kg-1.min-1), maximal myocardial blood flow was measured in 4 fetuses hypoxemic for a minimum of 5-8 days (pH = 7.33 +/- 0.01, arterial PCO2 = 49.8 +/- 4.2 Torr, arterial PO2 = 16.1 +/- 1.3 Torr, and arterial concentration of O2 = 5.3 +/- 1.2 ml/dl). These data were compared with an identically instrumented group of normoxemic fetuses (n = 7) following the same study protocol (pH = 7.38 +/- 0.02, arterial PCO2 = 43.1 +/ 3.8 Torr, arterial PO2 = 19.8 +/- 2.0 Torr, and arterial concentration of O2 = 7.9 +/- 1.0 ml/dl) (P < 0.05). At comparable arterial pressures, the maximal myocardial flow (ml.min-1.100 g tissue-1) for hypoxemic vs. normoxemic fetuses was 974 +/- 273 and 630 +/- 181 for the total myocardium, 986 +/- 367 and 602 +/- 192 for the left ventricular free wall, 1,025 +/- 346 and 614 +/- 178 for the septum, and 1,231 +/- 274 and 757 +/- 269 for the right ventricular free wall, respectively (P < 0.01). These data suggest that hypoxemia in the fetus can significantly alter the coronary vascular bed, which, if confirmed, would represent an important adaptation in the developing fetus. PMID- 1415782 TI - The endocardial endothelium. AB - The heart wall with its complex trabecular structures is covered with a very thin layer of endocardial endothelial (EE) cells. EE cells appear early during cardiac development; they are involved in myocardial trabeculation and the formation of primitive nutrient vessels. This process precedes the development of coronary vessels, Purkinje fibers, and nerve fibers. EE has a different cell shape and cytoskeletal organization than vascular endothelium. The differences in permeability between EE and the coronary vascular endothelium in the subendocardial myocardium might assign characteristic electrochemical properties to the endocardium. Modulation of EE function by substances in the blood constitutes an important intracavitary autoregulation of muscle-pump performance of the heart, i.e., by altering the duration of contraction without significantly altering early contraction dynamics. Such an autoregulation resets the timing of ventricular relaxation and rapid filling with little effect on early systolic contraction and ejection. Both the release by the EE of various substances with inotropic properties and a trans-EE physicochemical control are postulated as possible underlying mechanisms. PMID- 1415783 TI - Digital image analysis of shark gills: modeling of oxygen transfer in the domain of time. AB - Digital radiographic imaging of blood circulation through leopard shark gills establishes a secondary lamellar transit time of 6.5 s. This duration, combined with estimates of cardiac output and hemoglobin-oxygen affinity, permits novel modeling of gill oxygen transfer in the time domain. The temporal model allows assessment of factors contributing to previously noted discrepancies between physiological and morphometric branchial oxygen conductance estimates. Lamellar transit time for shark blood is 20 times greater than human alveolar transit time, and thus correlates with a slower rate of hemoglobin-oxygen binding and a greater diffusion distance. PMID- 1415784 TI - Atrial natriuretic factor binding sites in rat area postrema: autoradiographic study. AB - The area postrema (AP) is a brain stem circumventricular organ implicated, among other functions, in central cardiovascular (CV) regulation. Competition binding analysis performed by quantitative in vitro autoradiography demonstrated specific, high-affinity (Kd, 0.32 +/- 0.11 nM), low-capacity (Bmax, 57.5 +/- 10.9 fmol/mg protein) atrial natriuretic factor (ANF) binding sites in the AP. C-ANF [des-(Gln116-Gly120)ANF-(Arg102-Cys121)-NH2] and ANF-(Phe106-Ile113)-NH2 (two ligands endowed with selectivity for the ANF-C receptor), as well as C-type natriuretic peptide (CNP), did not compete noticeably at pathophysiological concentrations for 125I-ANF binding. 125I-[Tyr0]CNP bound to the AP to a much lower extent than 125I-ANF. Electron microscopic autoradiography in vivo disclosed that 125I-ANF was preferentially bound to axon, dendrite, and astrocyte plasmalemma. These studies demonstrate that the AP contains natriuretic peptide binding sites with pharmacological characteristics of the ANF-A and ANF-B but not of the ANF-C receptor subtype. In the AP, ANF interacts with those sites resembling ANF-A receptors. Cellular localization of these binding sites may relate to their possible involvement in the centrally mediated salt and water regulation and/or CV effects of circulating ANF. PMID- 1415785 TI - Vasopressin and angiotensin II in reflex regulation of heart rate: effect of water deprivation. AB - This study tested the hypothesis that endogenous angiotensin II (ANG II) and vasopressin enhance baroreflex-mediated increases in heart rate in water-replete dogs and in dogs water deprived to chronically elevate plasma ANG II and vasopressin concentrations. The baroreflex was assessed by examining the heart rate response to infusion of increasing doses of nitroprusside (0.3, 0.6, 1.5, and 3.0 micrograms.kg-1.min-1). The effect on the baroreflex of pretreating the dogs with the competitive ANG II antagonist saralasin, a V1-vasopressin antagonist, or a combined V1/V2-vasopressin antagonist, alone or in combination, was determined. Nitroprusside infusion produced dose-dependent increases in heart rate, and the heart rate response was greater in water-deprived dogs in association with higher plasma levels of ANG II and vasopressin than in water replete dogs. ANG II blockade alone depressed reflex increases in heart rate in water-deprived but not water-replete dogs. In both water-replete and water deprived dogs, blockade of V1-vasopressin receptors reduced the heart rate response to hypotension, but this effect could be produced only when ANG II receptors were also blocked. In addition, administration of saralasin and the V1/V2-vasopressin antagonist led to a further reduction of the reflex tachycardia. These data suggest that endogenous vasopressin, acting at both V1- and V2-receptors, can amplify the increase in heart rate produced by hypotension. In addition, the results further support a physiological role for chronic elevations in endogenous ANG II in the maintenance of normal baroreflex function. PMID- 1415786 TI - Roles of catecholamines and corticosterone during anoxia and recovery at 5 degrees C in turtles. AB - The roles of the catecholamines and corticosterone in glucose regulation during 28 days of submergence anoxia and air-breathing recovery at 5 degrees C in the turtle Chrysemys picta were examined. Anoxia resulted in an increase in mean plasma epinephrine and norepinephrine levels (from 42 and 49 to 966 and 3,826 pg/ml, respectively) and a decrease in hepatic glycogen levels. Despite the increase in plasma catecholamine levels, plasma glucose levels did not change, and the percent of the alpha form of hepatic glycogen phosphorylase was decreased compared with normoxic controls. Plasma levels of lactate increased from 1.5 to 95 mM, and corticosterone decreased during anoxia. During recovery in air, corticosterone returned to control levels within 1 day, and plasma lactate levels slowly decreased. In contrast to a previous study on anoxic turtles at 22 degrees C, at 5 degrees C the catecholamines do not stimulate hepatic glycogenolysis by increasing the level of glycogen phosphorylase alpha. The results do not support the hypothesis that corticosterone enhances lactate clearance from turtle plasma during recovery from anoxia. PMID- 1415787 TI - Stress in birds due to routine handling and a technique to avoid it. AB - The stress that might result in animals from the routine handling that most experimental studies involve, e.g., weighing, injecting, and blood sampling, is usually assumed to be minimal when the animals look quiet. However, the intensity of this stress remains largely ignored. We have developed a system that allows blood samples to be taken from freely behaving geese without entering the animal room. In these entirely undisturbed geese, the humoral indexes of stress, i.e., blood levels of catecholamines, corticosterone, and lactate, were as low or even lower than the lowest values previously reported for birds. Remarkably, the mean basal values for epinephrine and norepinephrine were 90-fold and 5-fold, respectively, below the lowest values in the literature. Stress-induced variations in pH that would have concealed detection of nutrition-induced changes in pH were eliminated. In contrast, even though the birds looked quiet during a short 5-min routine handling procedure, to which they had been accustomed for weeks, there was a dramatic increase in the level of humoral indexes of stress. These increased severalfold within only 2 min, and the return to initial values could take up to 1 h. Acid-base balance was also disrupted. Thus, in studies on animals, the absence of stress cannot be deduced from only behavioral observations. Only a system for taking blood without human interference may enable stress-free investigations. PMID- 1415788 TI - Early insulin response after food intake in geese. AB - Plasma glucose and insulin levels were measured in chronically catheterized, freely moving, undisturbed geese, which were offered a free standard meal after an overnight fast. The insulin level markedly rose within the first minute after the start of food ingestion, whereas plasma glucose did not increase. This early insulin response was not correlated with the size of the meal. In contrast, both postabsorptive insulin response and plasma glucose changes were dependent on meal size. When a small amount of food (2-6 g) was eaten, insulin returned to basal level within 30 min, whereas plasma glucose remained unchanged. Larger meals (15 20 g) maintained plasma insulin at a higher level and induced a sustained rise of plasma glucose. These results indicate that there is a cephalic phase of insulin secretion at the beginning of the meal in birds as previously described in mammals. PMID- 1415789 TI - Whole body insulin sensitivity in Osborne-Mendel and S 5B/Pl rats eating a low- or high-fat diet. AB - To determine whether whole body insulin sensitivity differs between a rat strain that does not (S 5B/Pl) and a strain that does [Osborne-Mendel (OM)] become obese when eating a high-fat diet, we performed euglycemic clamp studies in animals from each strain during low- and high-fat feeding. Clamps were performed after 2 days ("initial clamp") and 9 days ("final clamp") on each diet. Plasma glucose and insulin levels during the final 60 min of initial and final clamps were similar in S 5B/Pl and OM rats regardless of diet. Insulin sensitivity, measured as the glucose clearance rate during the final 60 min of the clamp, averaged 35 +/- 3 ml.kg-1.min-1 in S 5B/Pl rats after 2 days on a low-fat diet. This did not change significantly during an additional 7 days on the low-fat diet. The high fat diet was associated with a 13% reduction in insulin sensitivity after 2 days and a 30% reduction after 9 days in S 5B/Pl rats. OM rats exhibited similar patterns of insulin sensitivity during low- and high-fat diets, albeit at lower insulin sensitivity overall (P < 0.0005 vs. S 5B/Pl). Mean glucose clearance after 2 days on the low-fat diet was 27 +/- 2 mg.kg-1.min-1 and did not change significantly during seven more days of low-fat feeding. The high-fat diet was associated with a 19% reduction in glucose clearance after 2 days and a 38% reduction after 9 days in OM rats. The magnitude of reduction in insulin sensitivity during high-fat diets did not differ significantly between strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415790 TI - Reversal of high-fat diet-induced obesity in female rats. AB - The purpose of the present study was to test whether the degree of obesity or the duration of the obese state affects the reversibility of diet-induced obesity. This was accomplished by initially feeding adult female Wistar rats either a low fat diet (Chow) or one of two high-fat diets (HFDs; 30 and 60% of total calories as dietary fat; 30% HFD and 60% HFD, respectively). Fifty-four days, reversal 1 (R1), or ninety-seven days, reversal 2 (R2), later the HFDs were substituted with the low-fat control diet in subgroups of rats. Animals from all groups were sampled at three intervals: the start of R1 (R1 start), and the completion of R1 (R1 end) and R2 (R2 end). At the end of each interval the 60% HFD-fed group had increased body weight, carcass lipid content, and retroperitoneal and parametrial white adipose tissue (RWAT and PWAT) pad weight, fat cell diameter, and fat cell volume, but not fat cell number (FCN), compared with the other groups. The 60% HFD-fed rats also exhibited a marked and persistent hyperphagia that continued even as most of the indexes of obesity approached their maximal values (R1 end). The 60% HFD group had a transient increase in RWAT and PWAT lipoprotein lipase activity that followed the development of most obesity indicators. A clear intermediate level of obesity did not develop in the 30% HFD-fed group. Instead, these animals had nonsignificant increases in these measures of adiposity, making it impossible to test whether the severity of the obesity affected its reversibility in age-matched groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415791 TI - Metabolic state of the in situ perfused trout heart during severe hypoxia. AB - An in situ perfused heart preparation was used to study the effects of severe hypoxia in the rainbow trout, Oncorhynchus mykiss. Hypoxic trout hearts were capable of generating similar power outputs and ATP turnovers to normoxic counterparts at subphysiological work regimes. However, lactate efflux was 35 fold higher and glycolytic rate was calculated to be > 10-fold higher in hypoxic than in normoxic hearts. The surprising ability of trout hearts to withstand severe hypoxia appears to be related to the rapid removal of lactate and associated protons from the heart. An increase in power demand to normal in vivo levels caused rapid failure in hypoxic hearts. Failure was caused by a decline in stroke volume (contractility) and was not a consequence of heart rate deterioration. Hypoxia caused marked declines in the concentration of creatine phosphate but not ATP, and we suggest that an increase in intracellular phosphate was the primary cause of failure. PMID- 1415792 TI - Injection of cobalt protoporphyrin into the medial nuclei of the hypothalamus elicits weight loss. AB - Intracerebroventricular administration of small amounts (0.1 mumol/kg body wt) of cobalt protoporphyrin (CoPP), a synthetic analogue of heme, results in transient hypophagia and prolonged reduction in body weight of rats. Statistically significant hypophagia is detectable within 3 h of CoPP infusion. These changes are accompanied by prompt and sustained reductions in running wheel revolutions, a measure of spontaneous locomotor activity. Bilateral intrahypothalamic injections of CoPP at far lower doses (4 nmol/rat) resulted in similar findings following infusion into the paraventricular, dorsomedial, and ventromedial nuclei, but the compound had no such effect when injected into the thalamus or the lateral hypothalamic area. These effects were also observed following microinjection of the natural metalloporphyrin, heme, into the medial hypothalamic nuclei. Inorganic cobalt, iron, protoporphyrin, and magnesium protoporphyrin injected similarly were without such effect. These findings provide further evidence that the site of the previously described actions of CoPP in reducing food intake and body weight in rats resides, at least in part, in the medial hypothalamus. Furthermore, this study expands the spectrum of metalloporphyrins that act in the central nervous system to elicit these changes from synthetic compounds such as CoPP to heme, the natural, physiological metalloporphyrin. PMID- 1415794 TI - Effect of reproductive function on cold tolerance in deer mice. AB - Thermoregulatory responses were evaluated in male deer mice (Peromyscus maniculatus nebrascensis) after exposure to short photoperiod and either warm or cold ambient temperature (T(a)). Deer mice were chosen for this study because males exhibit differential reproductive responses to short day length (SD); this difference has a genetic basis, and both phenotypes are found within natural breeding populations. Deer mice undergoing SD-induced gonadal regression significantly improved their cold limit to -32.9 degrees C after exposure to SD/warm T(a) and to -47.4 degrees C after SD/cold T(a) exposure, relative to long day length/warm T(a) controls (-17.4 degrees C). In contrast, deer mice maintaining reproductive function despite SD exposure significantly improved cold limit to -27.2 degrees C only after exposure to SD/cold T(a), relative to controls (-16.3 degrees C). Maximum norepinephrine-induced nonshivering thermogenesis (NST) did not vary with reproductive state, indicating differences in cold tolerance were not due to capacity to produce heat by NST. Comparison between phenotypes of heat production during cold tolerance tests indicated that greater cold tolerance among mice exhibiting SD-induced gonadal regression can be accounted for by 1) lower rates of heat loss and 2) greater improvement of heat production. These findings suggest a functional relationship between reproductive function and seasonal thermoregulatory adjustments and indicate a significant cost to breeding during the winter months. PMID- 1415793 TI - Dynamics of gastric emptying during and after stomach fill. AB - Gastric contents were sampled at various points during and after intragastric infusions of glucose solution (6.25, 12.5, 25%) delivered at rates typical of normal ingestion in the rat. The postinfusion results were consistent with those reported in the literature in that glucose solute emptied at a relatively stable rate over time and across stimulus concentrations. During fill (1.0 ml/min; experiment 1), by contrast, solute (caloric) emptying rate increased about threefold as stimulus concentration was raised. For each concentration, emptying rate was uniformly higher during than after fill (approximately 4 times higher at the lowest concentration). In experiment 2, gastric emptying rate during 12-min intragastric infusions of 12.5% glucose varied directly with the volumetric rate (0.5, 1.0, 2.0 ml/min) at which they were delivered. These results show that different rules govern gastric emptying during and after stomach fill. The results also suggest that a large proportion of a liquid meal may empty before feeding is terminated and that variations in the rate of ingestion could affect the gastric/postgastric distribution of ingesta and, in turn, the satiation process. PMID- 1415795 TI - Calcium channel blockers inhibit amiloride-stimulated short-circuit current in frog tadpole skin. AB - The larval frog skin has a very high electrical resistance and a corresponding low rate of transepithelial ion transport. Amiloride, a blocker of sodium transport in adult skin, transiently stimulates rather than inhibits short circuit current (Isc) across larval skin. The time course and concentration response to amiloride and the effects of calcium channel blockers on Isc were studied with larval frog skin mounted in modified Ussing chambers. The amiloride (1 mM) transient was markedly blunted if the skin was previously exposed to low amiloride (0.01-0.1 mM) concentrations. The calcium channel blockers verapamil, nitrendipine, diltiazem, W-7, and lanthanum all blocked the amiloride transient. Diltiazem itself caused a rapid transient in Isc, indicating that it may be a partial agonist. These data suggest that the amiloride-stimulated cation channels rapidly desensitize in a manner similar to the acetylcholine receptor. The decline in Isc after amiloride stimulation could be caused by amiloride block of the open channel. Blockade of amiloride stimulation by well-known calcium channel blockers suggests that these larval cation channels may have some characteristics in common with calcium channels. PMID- 1415796 TI - Cerebrovascular and coronary effects of endothelin-1 in the goat. AB - In vivo and in vitro effects of endothelin-1 (ET-1) on cerebral and coronary vasculature of goats were examined and compared. In six anesthetized goats intravenous injections of ET-1 (0.1-0.8 nmol) increased arterial pressure, did not change the middle cerebral (MCA) and left anterior descending or left circumflex coronary (LCC) arterial blood flows (electromagnetically measured), and increased cerebral and coronary vascular resistances. In four other anesthetized goats intra-arterial injections of ET-1 (0.01-0.3 nmol) decreased the MCA flow less than the LCC flow (maximal reduction was 20 and 80%, respectively) and only the highest dose increased arterial pressure. In isolated segments from large arteries ET-1 (10(-11) to 10(-7) M) caused concentration dependent isometric contractions, the concentration causing 50% of the maximal effect and the maximal contraction being lower in cerebral arteries than in coronary arteries. The in vitro reactivity of both arteries was unaffected by endothelium removal or by indomethacin (10(-5) M). Therefore ET-1 produces cerebral and coronary vasoconstriction in vivo and in vitro, probably by acting directly on vascular musculature. Although the sensitivity is higher in isolated cerebral arteries than in coronary arteries, the reactivity in vivo could be lower in the cerebral circulation than in the coronary circulation to this endothelium-derived peptide. PMID- 1415797 TI - Hemodynamic effects of central angiotensin I, II, and III in conscious rabbits. AB - We have examined the hemodynamic effects of intraventricular angiotensins in conscious rabbits. Fourth ventricular injections of angiotensin II (ANG II, 8 fmol to 25 pmol) produced dose-dependent pressor responses at doses 400 times less than equipressor intravenous doses. Lateral ventricle administration of doses up to 1,000 pmol had little effect on mean arterial pressure (maximum +7 +/ 3 mmHg, P < 0.05, n = 9). Comparison of dose-response curves to ANG I, II, and III showed that all three had similar maximum pressor effects (27 +/- 3 mmHg), with ANG I being four times less potent than ANG II, and ANG III as potent as ANG II. Central pretreatment with the ANG-converting enzyme inhibitor enalapril abolished the pressor response to ANG I, suggesting that it was mediated entirely through ANG II. Examination of the hemodynamic changes after ANG I, II, and III in rabbits instrumented with aortic, mesenteric, or hindquarter flow probes showed that the rise in blood pressure to all three agents was due entirely to a decrease in total peripheral conductance, since cardiac output and heart rate fell. Peripheral conductance changes were not uniform, with the mesenteric bed showing an average 20 +/- 3% fall in conductance, while the hindquarter conductance increased (+12 +/- 3%). In sinoaortic-denervated rabbits, however, central angiotensins reduced conductance equally in the hindlimb and mesenteric beds, suggesting that the hindlimb dilatation in the baroreceptor intact rabbit was due to baroreflex buffering of the pressor effect. In conclusion, these studies suggest that the main sites for ANG effects on the cardiovascular system are located in the brain stem.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415798 TI - Does reducing the rate or efficiency of digestion reduce food intake? AB - Two strains of rats (Charles River CD and Lewis) were fed high-moisture (71% water) diets containing 50-300 mg acarbose/kg dry diet for 1-3 wk. Acarbose impaired carbohydrate digestion in both strains, as evidenced by increased fecal excretion and increased intestinal contents. For both strains the highest dose of acarbose tended to stimulate food intake, whereas an intermediate dose (100 mg/kg) inhibited food intake. The lowest dose (50 mg/kg) had no significant effect. In general the food intake-promoting effect of acarbose was more pronounced in CD rats, whereas the food intake-inhibiting effect of acarbose was more pronounced in Lewis rats. To determine whether increased intestinal bulk, due to undigested food, was responsible for the reduced food intake, another experiment was conducted in which Lewis rats were fed diets containing 5-25% cellulose. Although this level of cellulose should have increased fecal bulk to the same degree as acarbose, cellulose increased rather than decreased food intake. It is proposed that the presence of incompletely digested food in the digestive tract can inhibit food intake for several days. Because manipulating diet moisture altered energy intake without altering percentage of food excreted as feces, it is proposed that acarbose and diet moisture alter food intake by different mechanisms. PMID- 1415799 TI - Intraventricular CCK-8 reduces single meal size in the baboon by interaction with type-A CCK receptors. AB - Intraventricular cholecystokinin COOH-terminal octapeptide (CCK-8) decreases meal size in the meal-trained baboon. In the present study, we tested whether this action is mediated by CCK-A receptors, CCK-B receptors, or both. Intraventricular administration of the selective CCK-A receptor agonist A71623 at 1 and 10 nmol/kg suppressed 30-min meal size 69 +/- 22% and 75 +/- 7%, respectively. Additionally, intraventricular A71623 was equipotent to CCK-8 at 1 nmol/kg (% suppression of meal by CCK = 59 +/- 17). However, intraventricular administration of the CCK-B receptor agonist A63387 at 10 nmol/kg had no effect on 30-min meal size (% suppression = 18 +/- 29). Intravenous administration of 10 nmol/kg A71623 did not result in an alteration of meal size, but prandial plasma insulin and glucose responses were delayed and blunted. Basal plasma insulin levels doubled after intravenous administration of A71623. Both behavioral and metabolic responses to A71623 in the baboon are virtually identical to those we have previously observed after CCK-8 treatment. Thus we conclude that the predominant receptor population with which intraventricular CCK-8 interacts are type-A CCK receptors that are accessible to the ventricular system of the baboon. PMID- 1415800 TI - Effects of CGRP on baroreflex control of heart rate and renal sympathetic nerve activity in rabbits. AB - We examined the effects of intravenous infusion of calcitonin gene-related peptide (CGRP) and sodium nitroprusside (SNP) on baroreceptor afferent nerve activity, renal sympathetic efferent nerve activity (RSNA), and heart rate in alpha-chloralose-anesthetized rabbits. Baroreceptor afferent nerve activity was measured from aortic nerves during CGRP- and SNP-induced hypotension. Decreases in aortic nerve activity in response to decreases in mean arterial pressure were not different during CGRP and SNP infusion. Progressive infusion of CGRP (12-120 pmol.kg-1.min-1) increased RNSA by 83 +/- 14 (mean +/- SE), 175 +/- 26, 246 +/- 36, and 343 +/- 41%, and heart rate by 8 +/- 2, 24 +/- 3, 37 +/- 4, and 47 +/- 6 beats/min during falls of blood pressure of 5, 10, 15, and 20 mmHg, respectively. These increases in RSNA and heart rate produced by CGRP were significantly greater than those produced by SNP. The alterations in heart rate and RSNA with CGRP were reversed by restoring blood pressure with phenylephrine HCl. In rabbits with sinoaortic and vagal deafferentation, the responses of heart rate and RSNA to a fall of blood pressure were abolished during both CGRP and SNP infusion. Therefore, it is suggested that the facilitated responses of heart rate and RSNA during CGRP infusion occurred by way of the arterial baroreflex arc. PMID- 1415801 TI - Effect of age and blood pressure on the heart rate, vasopressin, and renin response to hypoxia in fetal sheep. AB - The purpose of these studies was to determine whether attenuating the increase in arterial and central venous pressure (CVP) during acute hypoxia can augment the renin and arginine vasopressin (AVP) responses to isocapnic hypoxia in chronically instrumented sheep fetuses. Young (122 +/- 2 days; n = 7) and old (133 +/- 1 days, n = 7) fetuses were exposed to hypoxemia (arterial PO2 = approximately 12-13 Torr) without and with attenuation of the increase in mean arterial pressure (MAP) and CVP with the simultaneous infusion of sodium nitroprusside (NP). NP did not attenuate the bradycardia induced by hypoxia. Plasma renin activity did not increase with hypoxia even when the potentially inhibitory effect of increased MAP and CVP was attenuated with NP. The AVP response to hypoxia was greater in the old fetuses. Furthermore, NP did augment the AVP response to hypoxia in the young but not old fetuses. We conclude that increases in MAP and CVP (i.e., baroreceptor input) do not influence the decrease in heart rate and lack of renin responses to acute hypoxia in the sheep fetus and that increased MAP and CVP seems to restrain the AVP response to hypoxia in younger sheep fetuses. PMID- 1415802 TI - Clonidine in the prepyriform cortex blocked anorectic response to amino acid imbalance. AB - Ingestion of imbalanced amino acid diets (IMB) has been associated with a decrease in norepinephrine (NE) concentration in the prepyriform cortex (PPC), an area essential for the anorectic response to IMB. Decreased NE could result from activity-induced release (and subsequent metabolism) of the transmitter. If activity of the NE system is important in the rat's anorectic response to IMB, reduced NE activity should result in increased IMB intake. Therefore, the feeding response to IMB was measured after injecting clonidine (Clon) into the PPC to inhibit NE release. At 3 and 6 h after Clon (1.0 and 1.5 micrograms/rat) injections, IMB intake was increased from 69 (the usual response to IMB in untreated animals) to > 100% of control intake. Effective injection sites did not include the gustatory neocortex, an area important for conditioned taste aversions. Thus activation of the NE system in the PPC may be associated with the initial reduced intake of IMB, suggesting that NE activity in the PPC has a role in the neural mechanisms that subserve recognition of amino acid deficiency. PMID- 1415803 TI - Elevated muscle acidity and energy production during exhaustive exercise in humans. AB - This study examined the effect of previous intense exercise on energy production during exhaustive exercise. Subjects (n = 6) performed dynamic knee extensor exercise to exhaustion twice (Ex1 and Ex2) separated by 16 min of recovery consisting of 10 min of rest, 3.5 min of very high-intensity intermittent exercise, and a further 2.5 min of rest. This resulted in an elevated muscle lactate concentration of 13.1 mmol/kg wet wt before Ex2. Muscle lactate concentration was the same at end of Ex1 and Ex2, but the accumulation of lactate and net lactate release during Ex2 was reduced (P < 0.05) by 67 and 38%, respectively. The time to exhaustion was 3.73 and 2.98 min, respectively, and the mean rate of net lactate production for Ex2 was lower (P < 0.05) than for Ex1 (4.6 +/- 1.2 and 9.6 +/- 1.7 mmol.min-1.kg wet wt-1, respectively). Leg O2 uptake was the same for Ex1 and Ex2. Muscle pH (6.85) was lowered (P < 0.05) before Ex2, but at the end of Ex2 (6.77) it tended (P < 0.1) to be higher compared with that at the end of Ex1 (6.73). In summary, the net lactate production rate is reduced but the aerobic energy production is not significantly altered when intense exercise is repeated. Fatigue and the lowered glycolysis do not appear to be caused by the elevated acidity per se before exercise. PMID- 1415804 TI - Developmental changes in hindlimb muscles and diaphragm of sheep. AB - In this study, plasma thyroxine, contractile and histochemical (adenosinetriphosphatase and NADH) characteristics of soleus (SOL), medial gastrocnemius (MG), and extensor digitorum longus (EDL) were examined in 140-day gestation fetal sheep and in 2-, 5-, and 30-day-old lambs and adult ewes. Electrophoretic separation of myosin heavy chains was also done on all muscles and the diaphragm. There were no differences in the twitch contraction and relaxation times of MG and EDL at the different ages; in contrast SOL contraction times were significantly shorter in the fetus and newborn than in the adult. Fast glycolytic fibers first appeared in EDL, MG, and diaphragm at 5, 30, and 5 days after birth, respectively. The proportion of slow oxidative fibers decreased after birth and with postnatal development in EDL, whereas they increased in MG and diaphragm. Plasma thyroxine concentrations were higher in the fetus and day old lambs than in 2-, 5-, and 30-day-old lambs or adult sheep. It is suggested that contractile specialization of the fast-twitch diaphragm, MG, and EDL is largely achieved in utero and is probably mediated by thyroid hormone. In contrast, SOL changed postnatally, probably influenced by the altered neural drive. PMID- 1415805 TI - Platelet-activating factor antagonists limit glycine changes and behavioral deficits after brain trauma. AB - Tissue damage after traumatic brain injury (TBI) results in part from delayed biochemical changes initiated by the insult. Platelet-activating factor (PAF) is an alkylphospholipid that has been implicated in tissue damage after cerebral ischemia. PAF is toxic to certain neuronal cell lines in culture, reduces cerebral blood flow, alters the blood-brain barrier, and can enhance phospholipid hydrolysis. The recent development of receptor antagonists to PAF permits examination of its possible role in delayed tissue injury after neurotrauma. Treatment with the PAF receptor antagonists BN 52021 and WEB 2170 before injury significantly enhanced neurological recovery after fluid percussion-induced TBI in rats. Pretreatment with WEB 2170 also significantly limited alterations in tissue water content and tissue glycine levels after trauma, and reduced posttraumatic levels of extracellular glycine in ipsilateral hippocampus. These findings implicate PAF in the pathophysiology of TBI, through actions at PAF receptors. A possible role for glycine in this process is suggested. PMID- 1415806 TI - Iron uptake in relation to transferrin degradation in brain and other tissues of rats. AB - The possibility that iron uptake by the brain involves transcytosis of the iron transferrin complex across the brain capillaries, followed by degradation of the transferrin (Tf) within the brain, was investigated using diferric 125I-[59Fe]Tf and [59Fe]Tf coupled to 125I-tyramine cellobiose (TC). The radiolabeled catabolic products of proteins labeled with 125I-TC remain in the cells where degradation occurs. The TCTf complex behaved normally with respect to its ability to donate iron to rat reticulocytes in vitro or to the brain, liver, kidneys, and femurs in vivo. In the brain there was little difference in the uptake of 125I derived from Tf and TCTf, and the amounts were equivalent to only a small fraction of the 59Fe uptake. Hence, the rate of Tf catabolism in the brain was insufficient to account for the rate of accumulation of iron from plasma Tf. It was concluded that Tf recycles to the plasma after delivering its iron to the brain. The uptake of 125I from TCTf by the liver and kidneys accounted for 40-50% of the total rate of Tf catabolism. This indicated that they were important but not the only sites of degradation of this protein. PMID- 1415807 TI - Gestational changes in Ca2+ transport across rat placenta and mRNA for calbindin9K and Ca(2+)-ATPase. AB - The unidirectional maternofetal clearance (Kmf) of 45Ca was measured across the rat placenta over the last one-third of gestation. Kmf for 45Ca normalized to its diffusion coefficient in water (Kmf/Dw) increased 72-fold between days 15 and 22 of gestation from 3.5 +/- 0.3 to 253.1 +/- 22.0 cm/g placenta, respectively. At 15 and 18 days of gestation, Kmf/Dw for 45Ca was similar to Kmf/Dw for the paracellular marker [14C]mannitol, but at 21 and 22 days of gestation, Kmf/Dw for 45Ca was significantly higher than Kmf/Dw for [14C]mannitol, indicating that an additional route of transfer, other than diffusion, becomes available to calcium during this period. Northern hybridization analysis demonstrated that rat placental calbindin9K-to-beta-actin mRNA ratio increased 135-fold between 15 and 22 days of gestation and was temporally associated with the gestational increase in Kmf/Dw for 45Ca. In contrast, rat placental Ca(2+)-ATPase-to-beta-actin mRNA ratio increased only two- to threefold over the same gestational period and did not mirror the gestational changes in calcium clearance. These trends suggest that the expression of placental calbindin9K, but not Ca(2+)-ATPase, may be rate limiting to placental calcium transport in the rat. PMID- 1415808 TI - Tissue-specific effects of physiological ANP infusion on blood-tissue albumin transport. AB - Blood-tissue transport of 131I-labeled bovine serum albumin (BSA) during intravenous infusion of synthetic atrial natriuretic peptide (ANP) was examined in anesthetized male Wistar rats. Plasma volumes were maintained at pre-ANP levels by infusion of 2% BSA in lactated Ringer solution (LR) to minimize compensatory responses to ANP-induced hypovolemia. 131I-BSA clearance was measured over 30 min, and 125I-BSA was injected terminally to correct for intravascular volume. Thirty-minute infusion of 20 ng.kg-1.min-1 ANP resulted in a tissue-selective increase in 131I-BSA clearance in jejunum and colon compared with controls given LR only. Smaller but significant increases in tracer clearance also were observed in fat, kidney, left ventricle, and skeletal muscle exposed to 400 ng.kg-1.min-1 ANP. The observed elevation in tracer albumin extravasation was not associated with any measurable increase in tissue extravascular water content. Furthermore, it was shown that coupling of 131I-BSA transport to filtration induced by hindlimb venous congestion was similar in control and ANP-treated rats. In a second series of experiments, plasma ANP levels were determined after 30-min ANP infusions from 0 to 180 ng.kg-1.min-1. Significant linear associations between physiological ANP levels (62-578 pg/ml) and 131I-BSA clearance were demonstrable for small intestine, colon, fat, kidney, and skeletal muscle but not for skin, heart, diaphragm, and lung. We conclude that raising plasma ANP by infusion of the synthetic peptide results in a filtration-independent, tissue-selective increase in albumin transport. Tissue uptake of albumin is a potential mechanism for extrarenal fluid shift during circulatory volume overload. PMID- 1415809 TI - Indomethacin attenuates exercise-induced proteinuria in hypertensive miniature swine. AB - Exercise-induced proteinuria may be increased in hypertensives. The mechanisms underlying the increased proteinuria are not known, and it has not been determined whether animal models of hypertension exhibit a similar response. We investigated whether indomethacin (Indo) altered exercise-induced proteinuria in normal and hypertensive deoxycorticosterone acetate (DOCA) Yucatan miniature swine (YMS). Five normal and four DOCA YMS underwent 30 min of treadmill exercise at 80% of maximal heart rate. Cumulative (exercise + recovery) albumin excretion in the DOCA YMS was 25-fold (P < 0.01) greater than observed in the normal YMS. Indo had no effect on resting or exercise-induced proteinuria in the normal YMS. However, Indo decreased the slightly elevated proteinuria at rest, and normalized the exaggerated exercise-induced proteinuria in the DOCA YMS. The antiproteinuric effect of Indo in the DOCA YMS was not associated with altered exercise, recovery blood pressure, or glomerular filtration rate. Thus hypertensive DOCA YMS exhibit an exaggerated exercise-induced proteinuria. It is suggested that eicosanoids are involved in this abnormal renal proteinuric response to exercise. PMID- 1415810 TI - A network model of respiratory rhythmogenesis. AB - A mathematical model of the three-phase respiratory network proposed by Richter et al. (News Physiol. Sci. 1: 109-112, 1986) is developed and its properties are examined. The model reproduces the experimentally determined trajectories of membrane potential for the five physiologically distinct types of neurons included. Stepwise parameter changes can produce a respiratory rhythm with only two separate electrophysiological phases, result in apnea, or produce more complex patterns of firing. The phase-resetting behavior of the model was obtained with perturbing stimuli and is comparable to experimentally determined phase-resetting data. There is reasonable agreement between model predictions and experimental results. In the model, the properties of the phase singularity make termination of the respiratory rhythm by an appropriately timed perturbation virtually impossible, which is in agreement with experimental observations. The rhythm can be stopped by alterations that simulate the effect of input from the superior laryngeal nerve; the rhythm is locked in the postinspiratory phase. We conclude that our results are consistent with the concept of a network oscillator as the source of the respiratory rhythm. PMID- 1415811 TI - Enzyme-linked immunosorbent assay of colostral IgG transported into lymph and plasma in neonatal pigs. AB - Amounts of colostral proteins in lymph and plasma were estimated by an enzyme linked immunosorbent assay (ELISA) after infusion of bovine colostrum into the duodenal lumen in nonsuckling neonatal pigs. The rate of immunoglobulin (Ig) G transport in lymph of the thoracic duct reached the maximal level (4.7 +/- 1.3 mg.15 min-1.kg body wt-1) within 3 h after the duodenal infusion. The rate of small protein (SP) transport more slowly increased than that of IgG. On the contrary, casein remained in the much lower level in lymph. IgG concentration in plasma increased gradually and reached a plateau level (2.5 +/- 0.9 g/l) 5 h after the infusion, but the levels of SP and casein were slowly and slightly increased in plasma. The IgG-to-casein and SP-to-casein ratios in lymph and plasma were 161:15:1 and 128:12:1 4 h after the infusion, respectively, and much higher than the value in the colostrum (IgG/SP/casein = 15:4:1). These results indicate 1) that IgG transported via lymph flow after absorption through the small intestine is faster than that via blood flow, 2) that the concentration of absorbed IgG is higher than that of absorbed SP and much higher than the concentration of absorbed casein both in the lymph and plasma, and 3) that total amount of colostral protein transported via blood flow is larger than that transported via lymph flow. PMID- 1415812 TI - Aging alters feedback effects of the activity-rest cycle on the circadian clock. AB - Two different stimuli (i.e., benzodiazepines and dark pulses) inducing phase shifts in the circadian clock of young hamsters through changes in the level of activity do not induce phase shifts in old hamsters, despite the fact that these stimuli induce a similar acute change in locomotor activity in young and old animals. In contrast, old hamsters remain sensitive to the phase-shifting effects of stimuli clearly not associated with any change in locomotor activity (i.e., protein synthesis inhibitors or light). Thus the circadian system of old animals becomes selectively unresponsive to synchronizing signals mediated by the activity-rest state of the animals. Previous age-related changes in circadian rhythmicity that have been observed in mammals, including humans, may be related to a weakened coupling between the activity-rest cycle and the circadian clock. PMID- 1415813 TI - Psychosocial rehabilitation and psychiatry in the care of long-term patients. AB - The relationship between psychosocial rehabilitation and psychiatry in the care of long-term mental patients is one that may often be characterized, at best, as an uneasy alliance. The author summarizes the basic concepts that define the discipline of psychosocial rehabilitation and discusses how those concepts have at times been distorted in actual practice. The article concludes with an analysis of the two disciplines' common ground in caring for long-term patients and a commentary on the benefits that each may offer the other. Together psychiatry and psychosocial rehabilitation hold the key to improved circumstances for realizing the promise of deinstitutionalization, which seems largely to have eluded us for the past several decades. PMID- 1415814 TI - The psychoanalytic conceptualization of perinatal loss: a multidimensional model. AB - Much has been learned about perinatal loss over the past 20 years through clinical investigations and quantitative research. However, a review of studies over the past decade reveals that perinatal loss is increasingly being seen in the same way as a death of any other member of the family, rather than as a unique bereavement. A comprehensive understanding of perinatal loss anchored in a theoretical framework of pregnancy is lacking. This article offers a multidimensional model for examining this loss by applying four psychoanalytic interpretations of pregnancy. 1) From the perspective of pregnancy ushering in the new developmental phase of parenthood, perinatal loss becomes a developmental interference, disrupting a significant milestone as well as causing isolation from peers. 2) In light of the usual recapitulation of earlier conflicts during pregnancy as noted by drive theory, perinatal loss may lead to an intensification of intrapsychic conflicts. 3) Understanding pregnancy as the creation of a specific person in an object relations model highlights the importance of mourning after perinatal death, as well as the need to tend to associated unresolved grief from earlier losses. 4) Finally, a model of narcissism describes how pregnancy reorganizes self-esteem, thereby delineating the intense narcissistic injury and rage that often follow perinatal loss. These multiple frameworks help to explain the many repercussions of this loss as well as to account for individual differences. Research findings are selectively reviewed to support the validity of this model. Conversely, this model may productively guide future avenues for research. PMID- 1415815 TI - Contested boundaries of bipolar disorder and the limits of categorical diagnosis in psychiatry. AB - The authors' primary objective is to outline the phenomenology, importance, and available data on issues concerning the boundaries between bipolar disorder and diagnoses such as schizophrenia, unipolar depression, and personality disorders. In addition, by illuminating the many difficulties with the boundaries of one of psychiatry's more robust diagnoses, they hope to awaken in the reader a healthy skepticism about current psychiatric nosology. For a topic of this scope, a literature review must be selective. For each boundary area, a mixture of classic and recent papers covering a range of validating criteria is included whenever possible. Good summary data are cited when available, as are a selection of relevant theoretical papers. The review indicates that current diagnostic criteria for bipolar disorder are generally reasonable, but there are many problem areas, most of which cannot be solved by changes in criteria. Notable among these are 1) the possibility of future manic episodes in unipolar disorder, 2) schizoaffective disorder, bipolar type, and 3) borderline personality disorder with prominent mood swings. The disputes concerning the boundaries of bipolar disorder illustrate the limitations of categorical diagnosis which result from the implementation of diagnostic criteria, the criteria themselves, the fundamental nosologic process, and the phenomena themselves. If these limitations are to be extended, it may be necessary to explore alternative ways of defining psychiatric diagnoses for different settings in research and clinical practice. PMID- 1415816 TI - Psychiatric outpatient practice: patterns and policies. AB - OBJECTIVE: The purpose of this paper is to explore possible consequences of recent changes in the Medicare payment schedule for office-based psychiatric services. METHOD: Psychiatric office visits from the 1985 National Ambulatory Medical Care Survey were categorized in a manner that approximates commonly used codes of the Physicians' Current Procedural Terminology. An analysis was conducted of the frequency and clinical characteristics of various types of services, focusing particularly on visits of under 20 minutes in length that included a medication prescription (medication visits) and other visits of 35 minutes or less in duration (brief visits). RESULTS: Medication visits and brief visits together accounted for more than one-quarter (27.3%) of all U.S. psychiatric office visits. The relative risk of receiving these short visits was greater for patients who paid with public resources, were over 65 years of age, were nonwhite in race (brief visits only), received a prescription for an antipsychotic medication, or were diagnosed as having a psychotic disorder. CONCLUSIONS: Short office visits are provided to a particularly vulnerable patient population. The reduction in Medicare copayments for medication management services should increase the patient demand for these short visits. However, where the new Medicare schedule has lowered physician fees for these services, the financial incentive to provide short visits will decrease and patient access may become limited. PMID- 1415817 TI - Regional cerebral glucose metabolism in bulimia nervosa. AB - OBJECTIVE: The authors' purpose in this study was to further delineate the character of cerebral metabolism in bulimia nervosa and to determine if functional links could be made between regional cerebral metabolism and the symptoms of depression, obsessive-compulsive disorder, and bulimia nervosa. METHOD: Regional cerebral glucose metabolism was measured by using positron emission tomography in 11 inpatients with bulimia nervosa and 18 normal comparison subjects matched in sex (all were women), age, and educational level. The bulimic patients were also tested for symptoms of major depression and obsessive-compulsive disorder. RESULTS: The patients with bulimia showed a correlation between lower left anterolateral prefrontal regional cerebral glucose metabolism and greater depressive symptoms. However, the orbitofrontal regional cerebral glucose metabolism of patients with bulimia was not greater than that of comparison subjects, nor was higher orbitofrontal metabolism correlated with greater obsessive-compulsive disorder symptoms. CONCLUSIONS: These findings lead to the conclusion that left anterior lateral prefrontal cortex hypometabolism varies with the depressive symptoms observed in bulimia but that temporal lobe hypermetabolism and asymmetries appear to be independent of the mood state. PMID- 1415818 TI - Coping with the threat of AIDS: the role of social support. AB - OBJECTIVE: There has been relatively little clinical research on how asymptomatic HIV-positive men cope with the threat of AIDS. The present study was intended to 1) describe the coping strategies used by asymptomatic HIV-positive homosexual men, 2) examine the relationship of coping to dysphoria and self-esteem, and 3) explore how race and social support correlate with coping. METHOD: The study group was composed of 52 asymptomatic HIV-positive homosexual men. A group of 53 HIV-negative homosexual men was used for descriptive comparison. Data on coping, social support, dysphoria, and self-esteem came from self-report measures; depression was also determined by interviews with the Hamilton Rating Scale for Depression. RESULTS: The authors found that 1) subjects primarily coped with the threat of AIDS by adopting a fighting spirit, reframing stress to maximize personal growth, planning a course of action, and seeking social support; 2) more helpless coping, less fighting spirit, and less personal growth were related to dysphoria and poor self-esteem, whereas denial was related to more depression, anger, and helpless coping; 3) satisfaction with one's social support networks and participation in the AIDS community were related to more healthy coping strategies (e.g., fighting spirit, personal growth); and 4) black subjects expressed more denial, more helplessness, and less social support. CONCLUSIONS: These results suggest that health professionals should encourage more adaptive coping strategies, help patients use existing sources of positive social support, and assist patients, particularly black patients, in finding community support networks. PMID- 1415819 TI - Psychopathology, hypnotizability, and dissociation. AB - OBJECTIVE: The purpose of the study was to replicate and extend previous findings regarding the hypnotizability of different clinical groups. METHOD: The authors compared the differential hypnotizability of four psychiatric groups--patients with dissociative disorders (N = 17), schizophrenia (N = 13), mood disorders (N = 13), and anxiety disorders (N = 14)--and one normal group of college students (N = 63). Hypnotizability was assessed by four different measures: the eye roll sign and the induction score of the Hypnotic Induction Profile, the Stanford Hypnotic Susceptibility Scale, Form C, and two self-ratings of hypnotizability. RESULTS: As predicted, dissociative disorder patients had significantly higher hypnotizability scores on all measures than all other groups. Schizophrenic patients, on the other hand, had significantly lower scores than normal subjects on the eye roll sign and induction score but not on the other measures of hypnotizability. Some other unpredicted between-group differences were also found. Nevertheless, despite the between-group differences, the intercorrelations between the various hypnotizability measures within the normal group were very similar to those observed in the combined patient groups. CONCLUSIONS: The findings suggest that routine hypnotizability assessment may be useful in the differential diagnosis of patients with dissociative disorders. PMID- 1415820 TI - A historical perspective on the role of state hospitals viewed from the era of the "revolving door". AB - OBJECTIVE: By focusing on the functioning of a state hospital throughout its existence, the author provides a historical perspective on the nature and causes of "revolving door" admissions. METHOD: Northampton State Hospital was chosen as a prototype, and data on characteristics of patients and patterns of hospital utilization were analyzed from three 10-year periods: 1880-1889, 1930-1939, and 1980-1989. The data for the first two time periods came from the hospital's admission and discharge logbooks and its annual reports; the material for the most recent decade was obtained from unpublished yearly reports generated by the hospital's medical records department. RESULTS: The hospital operated very differently in each of the decades analyzed, but only in the 1980s was recidivism a major finding. This was not, as has often been thought, due to problems or populations unique to the state hospital in the 1980s nor to the fact that in earlier eras the state hospital rarely discharged patients. The once-large asylum has been replaced by a facility rapidly admitting and discharging patients, many of whom have accumulated more than 10 lifetime admissions, in a pattern of care not previously noted. CONCLUSIONS: State hospitals have functioned in different yet questionable ways throughout their history. Their current role of providing a revolving-door pattern of care to a considerable population is rooted in a contemporary shift in ideology. This role for state hospitals appears to make no more sense than did their earlier role as neglected and neglectful asylums, and it should be reevaluated. PMID- 1415821 TI - Meta-analysis of subjective sensitivity to alcohol in sons of alcoholics. AB - OBJECTIVE: Meta-analysis was used to review the research literature on self reported sensitivity to alcohol among sons of alcoholic and among normal control subjects. METHOD: Computerized and manual searches identified 17 eligible independent articles; nine contained the information necessary to compute effect sizes, and additional data on two other studies were provided by authors in response to written and telephone requests. RESULTS: Findings from 10 studies indicated that sons of alcoholics report significantly less sensitivity to alcohol than normal control subjects overall and during the ascending (i.e., 0-35 minutes after alcohol) and descending (i.e., 40-240 minutes after alcohol) limbs of the blood alcohol curve. Response to placebo did not significantly distinguish these groups in the five studies that included such assessment. CONCLUSIONS: It may be appropriate to appraise the biological sons of male alcoholics that they may experience less subjective sensitivity to alcohol than other individuals, but it is not possible to predict whether any particular individual will experience such lower sensitivity. In addition, self-report data can be influenced by many factors, and further research that assesses multiple psychological and physiological measures and uses longitudinal designs is needed to determine the relationship between specific factors and the development of alcoholism. PMID- 1415822 TI - Cross-cultural differences in rating hyperactive-disruptive behaviors in children. AB - OBJECTIVE: To determine the extent to which the reported variations across countries in the prevalence of attention-deficit hyperactivity disorder are due to cultural differences among raters, the authors examined the degree to which mental health professionals in four countries differed in their ratings of hyperactive-disruptive behaviors in children. METHOD: Mental health professionals from China (N = 8), Indonesia (N = 12), Japan (N = 9), and the United States (N = 8) rated the presence and degree of hyperactive-disruptive behaviors in standardized videotape vignettes of four 8-year-old boys participating in individual and group activities. RESULTS: Chinese and Indonesian clinicians gave significantly higher scores for hyperactive-disruptive behaviors than did their Japanese and American colleagues. CONCLUSIONS: These findings suggest that perceptions of hyperactivity vary significantly across countries even if uniform rating criteria are applied. Without correction for these perceptual differences, cross-cultural prevalence rates of hyperactivity may not be comparable. PMID- 1415823 TI - Deterioration in premorbid functioning in schizophrenia: a developmental model of negative symptoms in drug-free patients. AB - OBJECTIVE: The authors examined the relationship between negative symptoms and premorbid variables in drug-free schizophrenic patients. METHOD: The authors studied 63 clinically stable male schizophrenic inpatients who were not receiving any psychoactive medication. The patients were classified as having negative, positive, or mixed symptoms, and their premorbid functioning during childhood, early adolescence, and late adolescence was assessed by using the Premorbid Adjustment Scale. Correlational analyses were applied to the classification and developmental models. RESULTS: Patients with negative symptoms had significantly lower levels of premorbid functioning during late adolescence and significantly greater premorbid deterioration between childhood and early adolescence. Correlational analysis revealed significant positive relationships between premorbid variables and negative symptoms. CONCLUSIONS: The data suggest that a deterioration in social and intellectual functioning between childhood and adolescence is associated with the development of a negative symptom syndrome in schizophrenia. The premorbid deterioration appears to be an early prodrome of the disorder. Whether this residual negative symptom syndrome is in some way related to the deficit syndrome of schizophrenia awaits a prospective study. PMID- 1415824 TI - Alprazolam plasma concentrations and treatment response in panic disorder and agoraphobia. AB - OBJECTIVE: The authors' goal was to evaluate the relationship between plasma concentrations of alprazolam and both treatment response and side effects in patients with panic disorder and agoraphobia. METHOD: Ninety-six patients with panic disorder and agoraphobia were treated at three sites in a 6-week, fixed dose, double-blind, placebo-controlled, dose-response study of 2 mg/day or 6 mg/day of alprazolam. Assessments were made of panic attacks, avoidance behavior, generalized anxiety, and global response. Blood samples were collected throughout the study and analyzed for alprazolam and other benzodiazepines. RESULTS: Patient compliance with the protocol was judged to be good on the basis of plasma concentrations. According to logistic regression analysis, the relationships between plasma alprazolam concentration and response, as reflected by number of panic attacks reported, phobia ratings, physicians' and patients' ratings of global improvement, and the emergence of side effects, were significant. However, there was no significant relationship between plasma alprazolam concentration and the degree of generalized anxiety symptoms. CONCLUSIONS: The authors conclude that plasma concentration of alprazolam is related to treatment response, particularly in panic attacks. The alprazolam concentration associated with treatment response or with emergence of a given side effect varied widely among individuals, highlighting the necessity for individualized dose adjustment to obtain optimal treatment response while minimizing side effects. PMID- 1415825 TI - Panic disorder history in the families of patients with angiographically normal coronary arteries. AB - OBJECTIVE: The authors evaluated the diagnostic validity of an interview-based panic disorder diagnosis in cardiology chest pain patients with angiographically normal coronary arteries. METHOD: Patient probands with normal coronary arteries (N = 65) were first contracted immediately after their normal angiogram and were given a structured diagnostic interview. On the basis of the results of the interview, probands were grouped as having panic disorder (N = 19), panic attacks that did not meet frequency criteria for panic disorder (N = 17), or no panic (N = 29). At a later time, patient probands were recontacted and given a structured family history interview that inquired about psychopathology in their first degree biological relatives (N = 544). RESULTS: As predicted, panic disorder was significantly more prevalent among the first-degree relatives of probands with normal coronary arteries diagnosed with panic disorder or panic attacks than among the family members of probands with normal coronary arteries without panic (17.4% versus 15.7% versus 4.0%). Family members of probands with panic attacks were significantly more likely to be diagnosed with major depression than were the family members of probands with no panic; however, differences did not reach significance for family members of the panic disorder proband group. Groups did not differ significantly in familial alcoholism. CONCLUSIONS: These data support the construct validity of an interview-based panic disorder diagnosis among patients with chest pain and normal coronary arteries and suggest that these patients could benefit from treatment for panic disorder. PMID- 1415826 TI - Phenomenology and course of psychiatric disorders associated with combat-related posttraumatic stress disorder. AB - OBJECTIVE: Studies indicate that chronic combat-related posttraumatic stress disorder (PTSD) is frequently associated with other psychiatric disorders. Questions regarding the nature and interrelationships of these conditions require clarification. The purpose of this study was to address primary and secondary illness relationships by focusing on the specific phenomenology and course of illness onset of PTSD comorbidity. METHOD: In order to minimize confounding factors, only outpatients without recent substance use disorders were included. Sixty subjects who had been exposed to severe combat stress including veterans of Vietnam and veterans of World War II or Korea, 15 of whom were former prisoners of war, received structured assessments over serial evaluations. RESULTS: PTSD was the most prevalent lifetime disorder followed by major depression, panic disorder, generalized anxiety disorder, and phobic disorder or symptoms. Endogenous-appearing features overlapping other clinical populations were common; however, some specific symptom patterns also were suggestive of traumatic influence. Unlike generalized anxiety disorder and past substance use, the mean onset of phobias, major depression, and panic disorder, respectively, occurred later than PTSD. CONCLUSIONS: These observations suggest that persistent conditions related to PTSD progress toward symptoms that are increasingly autonomous in their pattern of occurrence. PMID- 1415827 TI - Recovery and relapse from major depressive disorder in the elderly. AB - OBJECTIVE: Results from the National Institute of Mental Health (NIMH) Collaborative Study of the Psychobiology of Depression raised serious concerns about the longer-term prognosis for major depressive disorder in younger persons. However, little research has examined the prognosis for major depressive disorder in the elderly despite suggestions that they have poorer clinical outcomes than younger adults. The objective of this study was to 1) document rates of recovery and relapse from major depressive disorder in a large group of inpatient elderly and 2) compare recovery and relapse rates from major depressive disorder in the elderly with those in a mixed-age patient group from the NIMH collaborative study. METHOD: The psychiatric status of 127 elderly inpatients diagnosed with major depressive disorder by Research Diagnostic Criteria was evaluated for 1 year. The same diagnostic and follow-up method to assess psychiatric symptoms employed in the NIMH study were used. RESULTS: One year after study admission, 72% of elderly patients had recovered. Nineteen percent of recovered patients, however, had a subsequent episode of major depressive disorder. Recovery and relapse rates in the elderly did not significantly differ from those reported for the mixed-age group in the NIMH study. CONCLUSIONS: It is erroneous to single out the elderly as being more likely to have poorer longitudinal treatment outcomes than others. Study findings indicate the need for continued refinement of somatic and nonsomatic treatments for the elderly to improve rates of sustained recovery from depression. PMID- 1415828 TI - Prediction of outcome in mania by mood-congruent or mood-incongruent psychotic features. AB - OBJECTIVE: The aim of this study was to determine the significance of mood congruence of psychotic features in mania as a predictor of outcome. METHOD: Fifty-four patients with bipolar disorder were followed prospectively for 4 years after recovery from an episode of mania with psychotic features. Assessments of residential and occupational status, interepisode symptoms, and episode recurrences were made at 6 and 48 months after recovery. Categorical outcomes were evaluated by logistic regression and recurrence risk with survival analysis. RESULTS: Mood-incongruent psychotic features during the index manic episode predicted a shorter time in remission at 4 years (hazard ratio = 2.6), and Schneiderian first-rank symptoms predicted poor residential status at 4 years (odds ratio = 20.1). CONCLUSIONS: Differentiation of mood congruence of psychotic features in mania evidently has prognostic validity and, therefore, has utility as a nosological characteristic. PMID- 1415829 TI - Psychotic symptoms and suicidal behavior in hospitalized children. AB - Association of psychotic symptoms with suicidal behavior was studied in 90 hospitalized prepubertal children. Children with psychotic symptoms were more likely to have threatened or attempted suicide. The association of visual hallucinations with suicidal behavior was stronger than that of auditory hallucinations or psychotic ideation. The authors speculate that psychosis in general and visual hallucinations especially may be indicators of suicide risk among children. PMID- 1415830 TI - Amelioration of mitral valve prolapse after treatment for panic disorder. AB - Twenty panic disorder patients with mitral valve prolapse showed amelioration of prolapse on repeat echocardiogram after treatment for panic disorder. This effect was significant when compared to repeat echocardiograms in eight psychiatrically normal control subjects with mitral valve prolapse. PMID- 1415831 TI - Hyperventilation-induced cerebral ischemia in panic disorder and effect of nimodipine. AB - Basilar artery blood flow was measured by transcranial Doppler ultrasonography before and during hyperventilation in nine patients with panic disorder and nine normal comparison subjects. The hyperventilation-induced decrease in basilar artery blood flow was significantly greater in patients with panic attacks than in comparison subjects. Two patients with decreases in basilar flow greater than 80% were successfully treated with nimodipine, a centrally active calcium channel blocker. PMID- 1415832 TI - Accumulation of fluoxetine and norfluoxetine in human brain during therapeutic administration. AB - In vivo 19fluorine nuclear magnetic resonance spectroscopy was used to measure the brain concentration of fluoxetine and norfluoxetine in five patients with obsessive-compulsive disorder and three with major depression. The mean brain:plasma ratio of the parent drug plus the metabolite was significantly elevated to 2.6 (SD = 1.0) (95% confidence interval = 1.9-3.3). This accumulation may have implications for understanding both the therapeutic and the toxic effects of fluoxetine. PMID- 1415833 TI - Severity of cocaine dependence as a predictor of relapse to cocaine use. AB - The severity of cocaine dependence of 39 hospitalized patients was assessed by administering the Structured Clinical Interview for DSM-III-R. No significant relationship was found between severity of cocaine dependence and cocaine use at 3-month follow-up. These findings suggest that severity of cocaine dependence may be a poor predictor of relapse to cocaine use. PMID- 1415834 TI - Recovery from protracted depression in old age. PMID- 1415835 TI - Use of cocaine to prevent opiate withdrawal. PMID- 1415836 TI - Retinopathy and bright light therapy. PMID- 1415837 TI - Comorbidity of personality disorders. PMID- 1415838 TI - Obesity and multiple personality disorder. PMID- 1415839 TI - Obesity and multiple personality disorder. PMID- 1415840 TI - Automobile driving by psychiatric patients. PMID- 1415841 TI - Steroid use and aggression. PMID- 1415842 TI - Organic mental disorders. PMID- 1415843 TI - Organic mental disorders. PMID- 1415844 TI - Organic mental disorders. PMID- 1415845 TI - Organic mental disorders. PMID- 1415846 TI - Organic mental disorders. PMID- 1415847 TI - Dopamine in schizophrenia. PMID- 1415848 TI - Recall of mental sleep experience with or without prior verbalization. AB - We investigated whether verbalization of contents of mental sleep experience (MSE), just after awakening provoked during rapid eye movement (REM) sleep, facilitates subsequent recall in the morning. Twelve subjects were awakened four times in each of two experimental nights and alternately asked to recall, with or without concurrent verbalization, MSE contents preceding the awakening. In the morning, the subjects were asked to report MSEs both verbalized and nonverbalized during the night. If subjects were unable to provide a spontaneous morning report, they were prompted using a probe, which was the title given by the subjects to each MSE at the end of its verbalization or covert recall at night. Frequencies of spontaneous reports were high, regardless of whether MSEs had been previously verbalized or not. The proportions of spontaneous and probed reports were similar for verbalized and nonverbalized MSEs, but spontaneous morning reports were longer than probed ones, regardless of their previous verbalization. Spontaneous and probed morning reports corresponding to night reports shared similar linguistic structures (i.e., length of sentences and proportions of waking-related utterances, which are indicative of difficulty of retrieval for MSE contents) and had similar percentages of contents common to night and morning reports. These findings support the hypothesis that verbalization does not directly influence the further accessibility of MSE contents. PMID- 1415849 TI - Pavlov's conceptualization of learning. AB - Introductory texts in psychology create the misleading impression that I. P. Pavlov was concerned solely with conditioned reflexes. In fact, influenced by Woodworth's Contemporary Schools of Psychology (1931), Pavlov also became interested in learning. Pavlov proposed a two-factor learning theory according to which all learning was based on association, but conditioning and trial and error learning had specific functions. According to Pavlov, conditioned reflexes were temporary and unstable and therefore more flexible in the interaction of higher organisms with the changing environment. Trial and error learning provided knowledge and was relatively more stable. Scientific discovery was based on facts obtained by trial and error; valid relations were reinforced by experimental results, whereas incorrect relationships were extinguished. Some suggestions are made that would allow authors of introductory texts to describe more informatively the contributions of Pavlov to modern psychology. PMID- 1415850 TI - Joseph McVicker Hunt: 1906-1991. PMID- 1415851 TI - Induced abortion and health as a value. PMID- 1415852 TI - RU 486. PMID- 1415853 TI - Global microbial traffic and the interchange of disease. PMID- 1415854 TI - Commentary: the public health consequences of restricted induced abortion- lessons from Romania. AB - The question of whether abortion should be legal is currently being decided in many countries. Although much of the discussion has focused on ethical issues, the public health consequences should not be overlooked and should be addressed realistically and responsibly. Nowhere are the public health manifestations of restricted abortion more apparent than in Romania. The pronatalist policies of the Ceaucescu regime resulted in the highest maternal mortality rate in Europe (approximately 150 maternal deaths per 100,000 live births) and in thousands of unwanted children in institutions. PMID- 1415855 TI - Determinants of depressive symptoms in the early weeks after miscarriage. AB - OBJECTIVES: We tested whether and under what conditions miscarriage increases depressive symptoms in the early weeks following loss. METHODS: We interviewed 232 women within 4 weeks of miscarriage and 283 pregnant women and 318 community women who had not recently been pregnant. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: Among women who had miscarried, the proportion who were highly symptomatic on the CES-D was 3.4 times that of pregnant women and 4.3 times that of community women. Among childless women, the proportion of women who had miscarried who were highly symptomatic was 5.7 times that of pregnant women and 11.0 times that of community women. Women who had miscarried were equally depressed regardless of length of gestation; among pregnant women, depressive symptoms declined with length of gestation. Among women who had miscarried, symptom levels did not vary with attitude toward the pregnancy; among pregnant women, depressive symptoms were elevated in those with unwanted pregnancies. Prior reproductive loss and advanced maternal age (35+ years) were not associated with symptom levels in any cohort. CONCLUSIONS: Depressive symptoms are markedly increased in the early weeks following miscarriage. This effect is substantially modified by number of living children, length of gestation at loss, and attitude toward pregnancy. PMID- 1415856 TI - Trends in obstetric operative procedures, 1980 to 1987. AB - OBJECTIVES: Increasing rates of cesarean deliveries have received widespread attention in recent years, as concern in the United States about unnecessary surgical procedures has increased. However, little information has been published on the national trends of other operative obstetric procedures occurring during deliveries. METHODS: We analyzed data from the National Hospital Discharge Survey to examine trends in the use of forceps, vacuum extraction, and cesarean section from 1980 through 1987. RESULTS: The rate of cesarean sections increased by 48%, while the rate of forceps procedures declined by 43%. Although the risk of cesarean section was significantly increased for older women, the risk of forceps and vacuum extraction procedures did not vary by age. Women with private insurance were significantly more likely to receive a cesarean section (rate ratio [RR] = 1.2), forceps procedure (RR = 1.7), and vacuum extraction procedure (RR = 1.8) than were women without private insurance. CONCLUSIONS: As pressure mounts to decrease the national cesarean section rate from 24% to 15% by the year 2000, attention should also be given to surveillance of other operative delivery procedures. PMID- 1415857 TI - Changes in mammography use: economic, need, and service factors. AB - OBJECTIVES: The purpose of this study was to document changes in mammography use between 1987 and 1990 and assess the relationship of use to selected economic, need, and health system factors. METHODS: Independent random-digit-dialed telephone surveys of women between 52 and 75 years of age were conducted. RESULTS: Between 1987 and 1990, the proportion of women who had had a mammogram in the past year increased from 31% to 51%. Though income was significantly related to overall patterns of use, it was not associated with recent mammogram use in 1990. Women with a family history of breast cancer reported greater use at both times, as did women who reported having a regular physician (particularly a gynecologist or internist). When all other variables were controlled for, women were over nine times more likely to have had multiple and recent mammograms in 1990 than in 1987. CONCLUSIONS: Mammography use dramatically increased between 1987 and 1990. There were strong relationships between the type of regular physician and mammography screening and between economic and personal history and repeated and recent mammography use. PMID- 1415858 TI - Current cigarette smoking and risk of acute pelvic inflammatory disease. AB - OBJECTIVES: Further information is needed on modifiable factors associated with the occurrence of acute pelvic inflammatory disease (PID). Cigarette smoking has been implicated as a risk factor for PID sequelae, but the association between smoking and PID has yet to be fully examined. METHODS: We conducted a population based case-control study to evaluate smoking as a risk factor for acute PID. The case patients (n = 131) were women health maintenance organization (HMO) enrollees between the ages of 18 and 40 years who were treated for a first episode of PID. The control patients (n = 294) were randomly selected from the HMO enrollment files. RESULTS: Relative to never smokers, current smokers were at increased risk of PID. Women who smoked 10 or more cigarettes per day had a higher risk than did those who smoked less. Available data indicate that smoking status is not serving as a marker for uncontrolled confounding by lifestyle factors. CONCLUSIONS: Our study results suggest that smoking represents a modifiable risk factor for acute PID. PMID- 1415859 TI - Lead exposure and child behavior. AB - OBJECTIVES: Unlike cognitive impairments associated with lead exposure, lead associated child behavior problems have been difficult to specify, particularly in young children. METHODS: The Child Behavior Checklist (CBCL) and the Center for Epidemiologic Studies Depression Scale were used as the outcome and confounding variables, respectively, of major interest. These measures were examined with respect to blood lead levels of 201 African-American children aged 2 through 5 years. RESULTS: In comparison with the low exposed group, the high exposed group (two consecutive blood lead levels greater than or equal to 15 micrograms/dL) had a significantly higher mean CBCL Total Behavior Problem Score (TBPS) and Internalizing and Externalizing scores; when other factors, including maternal depressive symptomatology, were controlled for, regression procedures indicated a .18-point TBPS increase for each unit increase in lead and a 5.1 point higher TBPS in the high exposed group; children in this group were 2.7 times more likely to have a TBPS in the clinical range. CONCLUSIONS: Through its use of a standardized parent-report measure of behavior and its consideration of maternal morale in multiple linear and logistic regression procedures, this study provides further evidence of lead's detrimental effect on child behavior at levels typical of present-day exposure. PMID- 1415860 TI - Pregnancy among the Hmong: birthweight, age, and parity. AB - OBJECTIVES: The influx of Southeast Asians into the United States allows for the study of this special population and contributes to a broader understanding of reproductive health. METHODS: We used information on birth certificates to identify 1937 Hmong children born 1985 through 1988 in California, and we compared birthweight and reproductive factors as related to these children with the same factors as related to 3776 White, non-Hispanic children born in the same period. RESULTS: Mean birthweight among Hmong children (3311 g) was significantly lower (P less than .05) than among White children (3452 g), but the proportion of births under 1500 g was higher for Whites. Hmong women were of much higher parity and were more likely to deliver at both a young (less than 18 years) and an old (greater than 40 years) maternal age. At every age and every parity, however, Hmong women had cesarean sections at one-half to one-tenth the rate of White women. CONCLUSIONS: Despite a high proportion of births at high parity and advanced maternal age, Hmong women gave birth to very low-birthweight babies at essentially the same rates as White women. Their lower cesarean section rates, however, deserve further attention. PMID- 1415861 TI - Neonatal tetanus in rural Bangladesh: risk factors and toxoid efficacy. AB - OBJECTIVES: Tetanus continues to be a leading cause of neonatal death in Bangladesh as in other developing countries, yet little is known about risk factors or the efficacy of tetanus toxoid in this setting. METHODS: In May 1990, mothers of 6148 infants born alive between March 15, 1989, and March 14, 1990, in 30 rural unions of Rajshahi Division in Bangladesh were interviewed. Three surviving controls for each neonatal tetanus death were matched for sex, residence, and date of birth. RESULTS: Of 330 neonatal deaths, 112 met the case definition for tetanus. Risk was increased with a history of neonatal tetanus in a previous child, application of coconut oil to the vagina, and use of multiple ties on the umbilical cord. Risk was reduced by the birth attendant washing hands and using a cleaned cord-cutting tool. Risk was not reduced by a maternal history of two doses of tetanus toxoid (TT2), although estimated efficacy of TT2 was 45% (95% confidence interval = 16% to 64%). Subsequent to the survey, a reference laboratory reported to potency in three consecutive lots of tetanus vaccine from the production laboratory in Bangladesh. CONCLUSIONS: These findings identify high-risk mothers, stress the importance of washing hands and cleaning the cord cutting tool, and demand improved quality control of tetanus vaccine production. PMID- 1415862 TI - Improving estimates of HIV-1 seroprevalence among childbearing women: use of smaller blood spots. AB - OBJECTIVES: Nationwide, human immunodeficiency virus type 1 (HIV-1) seroprevalence surveys using dried neonatal blood specimens are critical to estimating HIV-1 seroprevalence among childbearing women. However, the noninclusion of blood specimens deemed "quantity not sufficient" (QNS) for HIV-1 antibody testing potentially introduces bias. In Wisconsin beginning in 1990, we modified the survey protocol to reduce QNS rates and assess bias introduced by QNS specimens. METHODS: The HIV-1 antibody assay was modified to use four 1/8-in blood spots when a single 1/4-in blood spot could not be obtained. Both methods obtain identical blood volumes for testing. RESULTS: During a 27-month period, 7396 (4.8%) of 154,683 specimens were deemed QNS using 1/4-in blood spots. Of these, 6590 (89%) were of sufficient quantity to be tested using four 1/8-in blood spots; 6 (0.09%) specimens tested with 1/8-in blood spots were HIV-1 Western blot assay positive compared with 44 (0.03%) of 147,287 1/4-in specimens (odds ratio = 3.0; 95% confidence interval = 1.2, 7.4). CONCLUSIONS: Because noninclusion of QNS specimens potentially introduces bias, incorporating the results of HIV-1 antibody testing of QNS specimens using four 1/8-in blood spots can improve the accuracy of HIV-1 seroprevalence estimates in these serologic surveys. PMID- 1415863 TI - The disclosure of celebrity HIV infection: its effects on public attitudes. AB - OBJECTIVES: Despite the magnitude of the acquired immunodeficiency syndrome (AIDS) epidemic, studies have shown low levels of public concern about human immunodeficiency virus (HIV)/AIDS. We investigated the effects of celebrity disclosure of HIV infection on the AIDS-related perceptions of urban men. METHODS: Measures of AIDS-related perceptions were collected from 361 men waiting for mass transportation in downtown Chicago; 252 were assessed at three time points prior to and 109 were assessed at two time points after professional basketball star Earvin "Magic" Johnson's disclosure of his HIV infection. RESULTS: Significant increases in concern about AIDS, interest in AIDS information, and talking with friends about AIDS occurred after celebrity disclosure of HIV infection. CONCLUSIONS: Celebrity disclosure of HIV seropositivity demonstrated a marked change in AIDS-related perceptions among the men surveyed. Changes in awareness due to celebrity disclosure may lead to increased readiness to reduce risk and could be viewed as a window of opportunity for HIV prevention efforts. PMID- 1415864 TI - Legal blindness among 10-year-old children in Metropolitan Atlanta: prevalence, 1985 to 1987. AB - The prevalence of legal blindness in 10-year-olds in metropolitan Atlanta was 6.8 per 10,000 during 1985 to 1987. The prevalence was 8.8 per 10,000 in Black boys, 8.6 per 10,000 in White boys, 6.7 per 10,000 in White girls, and 1.8 per 10,000 in Black girls. Retinopathy of prematurity was the most common known cause (1.0 per 10,000). Of the 61 cases, 40 had other disabilities, including 14 with mental retardation, cerebral palsy, and epilepsy. The low prevalence among Black girls and the frequent occurrence of blindness with other disabilities are noteworthy. PMID- 1415865 TI - Sudden infant death syndrome and maternal smoking. AB - Data from Missouri for the period 1980 to 1985 suggest a dose-response relationship between smoking during pregnancy and the incidence of sudden infant death syndrome (SIDS). However, data from the National Institute of Child Health and Human Development SIDS Cooperative Epidemiological Study did not support a dose-response relationship. Neither the Missouri data nor the Cooperative Study data support a relationship between the age of occurrence of SIDS and smoking during pregnancy. PMID- 1415866 TI - Stage at diagnosis in breast cancer: race and socioeconomic factors. AB - Cancer incidence data from three US metropolitan areas were coupled with census tract indicators of education and income. The data suggest that both Black and White cancer patients living in census tracts with lower median education/income values are diagnosed in later disease stages than are patients in tracts with higher median education/income values. Within education and income strata, Black women had a less favorable stage of disease at diagnosis than Whites. The exception was in upper education/income levels, where the disadvantage for Blacks disappeared. These data provide additional evidence that women of low socioeconomic status could benefit from targeted screening. PMID- 1415867 TI - Measuring the use of mammography: two methods compared. AB - Population studies often estimate mammography use using women's self-reports. In one North Carolina county, we compared self-report surveys with a second method- counting mammograms per population--for 1987 and 1989. Estimates from self reports (35% in 1987, 55% in 1989) were considerably higher than those from mammogram counts (20% in 1987, 36% in 1989). We then confirmed 66% of self reports in the past year. Self-reported use is more accurate regarding whether a woman has had a mammogram than when she had it, but self-reports accurately measure change over time. PMID- 1415868 TI - Women with multiple sexual partners: united states, 1988. AB - Women who have multiple sexual partners in a short time period are appropriate targets for sexually transmitted disease (STD) prevention. We analyzed survey data collected in 1988 from a nationally representative sample of 8450 American women aged 15 to 44 to identify markers of such behavior. Among sexually active persons, 0.4% of married women and 8.4% of unmarried women had two or more sexual partners in the 3 months preceding the interview; unmarried marital status, early age at first sexual intercourse, lack of religious affiliation, and young age were associated with this behavior. All except young age were predictive after multivariate analysis. Such factors may help define women at elevated STD risk and allow better targeting of STD prevention. PMID- 1415869 TI - The medical origins of homelessness. AB - In 1989 through 1990, we conducted a cross-sectional survey of 1437 homeless adults in northern California (98% response rate). Prevalences of alcohol abuse, illegal drug use, and psychiatric hospitalization when adults first became homeless were 15% to 33% lower than prevalences following homelessness. The largest differences between the homeless and a comparison group of 3122 nonhomeless adults were for psychiatric hospitalization (odds ratios [ORs] of 4.6 for men and 5.9 for women) and alcohol abuse (ORs of 2.3 for men and 4.0 for women). However, when prehomeless prevalences of addictive and psychiatric disorders were compared with prevalences among the nonhomeless, absolute differences were no greater than 12%. PMID- 1415871 TI - Controlling cardiovascular disease: the role of the local health department. PMID- 1415870 TI - The search for meaning: RU 486 and the law of abortion. AB - The advent of RU 486 (mifepristone), a steroid analogue capable of inducing menses within 8 to 10 weeks of a missed menstrual period, has provoked a firestorm of concern and controversy. When used in conjunction with prostaglandin (RU 486/PG), it is at least 95% effective. Used in France principally to terminate confirmed pregnancies very early in the process of gestation, RU 486 raises many interesting legal questions. This article focuses on whether and how RU 486/PG can be accommodated within the framework of the world's current abortion laws. Four avenues are explored and conclusions drawn. First, it is clear that RU 486/PG can be used readily, if approved, within the regimens established by liberal abortion laws, as has been the experience in France, the United Kingdom, and even China. Second, although unlikely, the introduction of this new technology may inspire a reexamination of restrictive abortion statutes themselves. Third, some of the presently restrictive laws may be interpreted to permit RU 486/PG use as a legal procedure, for a very narrow range of reasons. Finally, in some settings the early use of RU 486/PG (before pregnancy can be confirmed) may fall outside the reach of abortion legislation and hence be acceptable from a legal point of view. PMID- 1415872 TI - Implementing the Veterans Administration's no-smoking policy. PMID- 1415874 TI - The accuracy of pharmacists' HIV and condom counseling. PMID- 1415873 TI - Screening behaviors among relatives of breast cancer patients. PMID- 1415875 TI - Site assessment of youth access to cigarette vending machines. PMID- 1415876 TI - An additional focus for the future. PMID- 1415877 TI - Diagnostic value of ultrasonography in partial ruptures of the Achilles tendon. AB - We evaluated 37 patients with surgically treated Achilles tendon disorders, comparing findings of preoperative ultrasonography with findings at surgery, to investigate the reliability of ultrasonography in diagnosing partial ruptures of the Achilles tendon. Discontinuity of tendon fibers, focal sonolucencies, and localized tendon swelling were positive findings suggestive of partial ruptures. We found the use of ultrasonography to be safe and reliable, with a sensitivity of 0.94, a specificity of 1.00, and an overall accuracy of 0.95. PMID- 1415878 TI - Osseous injury associated with acute tears of the anterior cruciate ligament. AB - Multiplanar spin-echo magnetic resonance imaging was performed on 54 patients with acute complete anterior cruciate ligament tears. Imaging was done within 45 days of index anterior cruciate ligament injury. Spin-echo T1- and T2-weighted images were used to determine the lesion morphology and location. Only the T2 weighted sagittal images were used for the incidence assessment; T2-weighted spin echo imaging reflects free water shifts and best indicates the acute edema and inflammatory changes from injury. Eighty-three percent (45 of 54) of the knees had an osseous contusion directly over the lateral femoral condyle terminal sulcus. The lesion was highly variable in size and imaging intensity; however, the most intense signal was always contiguous with the subchondral plate. Posterolateral joint injury was seen in 96% (43 of 45) of the knees that had a terminal sulcus osseous lesion determined by magnetic resonance imaging. This posterolateral lesion involves a spectrum of injury, including both soft tissue (popliteus-arcuate capsuloligamentous complex) and hard tissue (posterolateral tibial plateau) injuries. The consistent location of the osseous and soft tissue injuries underscores a necessary similar mechanism of injury associated with these acute anterior cruciate ligament tears. Based on these characteristic findings, several proposed mechanisms of injury are discussed. PMID- 1415879 TI - Partial rupture of the patellar ligament. AB - Eighty-one patients with 91 partial ruptures of the patellar ligament verified by ultrasonography were treated conservatively with a standardized training program based on the principles of eccentric loading. The partial ruptures were quantified by measuring the length of the hypoechoic lesion using ultrasonography in longitudinal projection. The partial ruptures were then divided into three groups: Grade I (less than 10 mm), Grade II (10 to 20 mm), and Grade III (greater than 20 mm). The results after the training program were significantly better in Grade I ruptures than in Grades II and III. The overall need for surgery was 29.6%: highest in Grade III ruptures (38.5%) and lowest in Grade I ruptures (6.6%). The outcome of conservative management, as well as the need for surgery of partial ruptures of the patellar ligament, may to some extent be predicted by the use of ultrasonography. PMID- 1415880 TI - Posterior shoulder instability. Surgical versus conservative results with evaluation of glenoid version. AB - We conducted a retrospective study on 50 patients with recurrent posterior shoulder instability. Twenty-five patients were treated conservatively with a specific rehabilitation program strengthening the rotator cuff. The other 25 patients, who did not improve with rehabilitation, underwent surgical reconstruction, the majority of these being soft tissue repairs. Recurrence in the surgically treated group averaged 72% while that in the conservatively treated group was 96%. However, 50% of those patients treated surgically and 68% of those treated conservatively felt their symptoms were improved. In view of the high recurrence rate with soft tissue reconstruction, computed tomography scans were obtained to evaluate glenoid version. Those patients with posterior shoulder instability were found to have increased glenoid retroversion when compared to an uninjured population (P less than 0.05). Our conclusions based on this study were that 1) specific therapy in the form of rotator cuff strengthening should be the initial form of treatment in patients with posterior shoulder instability, 2) soft tissue surgery has a high rate of recurrence, 3) the return to sports is variable, 4) there appears to be an increased incidence of glenoid retroversion in this patient population, and 5) the incidence of posttraumatic arthritis is low. PMID- 1415881 TI - The effect of in situ freezing on rabbit patellar tendon. A histologic, biochemical, and biomechanical analysis. AB - Cell necrosis has been well documented as one of the many changes that occur in autogenous tendon when it is used to reconstruct the anterior cruciate ligament. The purpose of this experiment was to isolate cell necrosis as a variable and study its effect on the patellar tendon. To accomplish this, both knees of 25 New Zealand White rabbits were operated on. In one knee, a 5-mm wide band of patellar tendon was subjected to two rapid freeze-thaw cycles, while the other knee underwent sham surgery. Histologic evaluation showed a zone of necrosis at 2 and 4 weeks with cellular repopulation complete at 8 weeks. patellar tendon cross sectional area was 0.118 cm2 at 8 weeks for the frozen specimens compared to 0.102 cm2 for the sham-operated controls. This difference was significant at the P = 0.025 level. Mechanical testing at 4 and 8 weeks revealed no significant changes in tendon length, maximum load, or stiffness. The collagen content was also unchanged at both 4 and 8 weeks. PMID- 1415882 TI - An injection technique to create a bloodless field in arthroscopically assisted anterior cruciate ligament reconstruction. AB - We did a retrospective study of 67 patients who had arthroscopically assisted anterior cruciate ligament reconstruction using the middle one-third of the patellar tendon to evaluate a technique for creating a bloodless field using a local anesthetic with epinephrine injection (the injection technique). For 37 patients, the bloodless field was created using the injection technique. In 30 others, hemostasis was achieved in the usual fashion with the pneumatic tourniquet. All patients underwent general anesthesia. Mean operative time and length of hospital stay was similar for each group. Mean postoperative pain medication consumption was significantly decreased for patients treated with the injection technique. No clinically recognizable complications could be attributed to either technique. We conclude that subcutaneous and intraarticular injection of local anesthesia with epinephrine is a satisfactory method of establishing a bloodless field in arthroscopically assisted anterior cruciate ligament reconstruction operations. PMID- 1415883 TI - Exercise performance of collegiate rodeo athletes. AB - In this study we examined the physical, hematologic, and exercise response of 20 male and 10 female athletes of the National Intercollegiate Rodeo Association, Central Rocky Mountain Region. Male subjects were grouped by roughstock, steer wrestling, and roping events. Female athletes were grouped separately. Maximal aerobic capacity, pulmonary ventilation, respiratory exchange ratio, energy expenditure, maximal heart rate, blood pressure, treadmill time, pre- and postexercise lactate, percent body fat, lean body mass, blood chemistry, serum lipids, and reaction/movement time were analyzed by event. No significant differences (P greater than 0.05) were found in any of these categories between male events. Mean resting blood chemistry parameters of rodeo athletes were within normal ranges. Steer wrestling athletes possessed greater body size and lean body mass than other groups. When analyzing body composition, blood pressure, and total cholesterol:high-density lipoprotein (HDL) cholesterol ratios, results indicate average to low risk for coronary heart disease. When compared to other intermittent-activity sport athletes, college rodeo athletes appear to have similar aerobic capacities, but possess lower lean body mass and greater percent body fat. PMID- 1415885 TI - Arthroscopic meniscectomy in patients over the age of 40. AB - One hundred eighteen patients, aged 40 or older, underwent partial meniscectomy and limited debridement of coexisting grade III or grade IV degenerative articular cartilage lesions. No curettage, abrasion arthroplasty, or subchondral drilling was performed. The average age of the patients was 57 years (range, 40 to 78). The mean followup was 3.3 years (range, 1 to 7). Sixty-three similar patients who also underwent partial meniscectomy but did not have the finding of significant coexisting articular surface erosion were studied for comparison. Of the 118 patients in the group with articular lesions (78 men and 40 women), 71 (60%) rated their improvement as significant, 22 (19%) as moderate, and 15 (13%) as mild; 10 (8%) noted no improvement. Although 98 (83%) were generally satisfied with their result, only 57 (48%) reported satisfaction for sports. However, 89 (75%) had resumed and continued recreational athletic activities. Results tended to be worse in women, in patients older than 60, in those with moderate or severe tibiofemoral radiographic changes, those who had a grade IV articular lesion, and those with longer followup time. Although results were poorer in patients with coexisting grade III or grade IV degenerative arthritis, arthroscopic partial meniscectomy and limited debridement was an acceptably effective procedure in patients over the age of 40. PMID- 1415886 TI - Occurrence of free nerve endings in the soft tissue of the knee joint. A histologic investigation. AB - We present a comprehensive histologic study of neurologic structures in 18 static and dynamic knee structures of 8 cadaveric knees. Qualitative and quantitative measurements of the incidence of free nerve endings in the structures were recorded. The highest amounts of afferent nerve fibers type IVa were found in the retinacula, the patellar ligament, the pes anserinus, and in the ligaments of Wrisberg and Humphry; the lowest amount was found in the anterior cruciate ligament. There is a positive correlation between the number of mechanoreceptors per standardized area unit and the clinical presentation of certain knee disorders. PMID- 1415884 TI - A biomechanical evaluation of taping and bracing in reducing knee joint translation and rotation. AB - We used five randomly selected cadaver specimens to evaluate the Anderson Knee Stabler and the Lenox Hill Knee Brace, individually and in combination with an anterior cruciate ligament protective tape method. Reduction of total laxity, as well as a defined pathologic anterior-posterior translation and internal-external rotation, was tested after the anterior cruciate and medial collateral ligaments of the specimens had been sectioned. Displacements were produced pneumatically; loads were applied to the tibia with the knee in 50 degrees of flexion. The tape and Lenox Hill Brace combination showed the greatest reduction in both anterior posterior translation and internal-external rotation. The Lenox Hill Brace and the tape method used individually both restricted anterior-posterior translation and internal-external rotation better than the Stabler Brace alone. This study provides objective evidence of the restraining capabilities of these protective systems that may prove to be beneficial in the clinical setting. PMID- 1415887 TI - The effect of exercise on patellar tracking in lateral patellar compression syndrome. AB - The influence of a physical therapy program on pain and patellar tracking was investigated clinically and radiologically with tangential views in 51 knees with lateral patellar compression syndrome. A pretest-posttest design was used to evaluate physical measurements of patellar alignment in subjects who had had patellofemoral pain for a minimum of 6 weeks. Eighty-four percent of the subjects were pain-free after an average of 8 weeks of rehabilitation or 11 physical therapy visits, with a mean quadriceps strength to total body weight ratio of 61% in women and 86% in men. The pretest-posttest difference in Merchant's congruence angle was significant at a probability of 0.0066 in the patients who were pain free after exercise, demonstrating less lateral patellar tracking. The pretest posttest difference in iliotibial band flexibility was significant at a probability of 0.0017, with the patients who were pain-free after exercise becoming more flexible. No significant differences were observed from before to after exercise in the patellofemoral index, Q angle, hamstring flexibility, thigh measurement, sclerotic subchondral bone, or sulcus angle. We were unable to predict which subjects would become pain-free with exercise by patellar position because the group that improved began more laterally tilted. The results of this study indicate that patellar tracking is improved with vastus medialis oblique strengthening, iliotibial band stretching, and joint mobility exercise in the majority of subjects with lateral patellar compression syndrome. PMID- 1415888 TI - Handball injuries. An epidemiologic and socioeconomic study. AB - A total of 570 injuries in handball players were prospectively registered in a well-defined geographic area of 124,321 inhabitants. The incidence of handball injuries was 46 per 10,000 inhabitants per year. The incidence in women (61 per 10,000 per year) was double that of men (31 per 10,000 per year). Sixty-two percent of the injuries were ligament sprains and tears and 12% were fractures. A total of 7% of the patients were hospitalized and the total loss of income because of sick leave was $3870. Sixty-eight percent of the injured handball players were absent from handball more than 1 week. Surprisingly, 8% of the minor injuries resulted in a sick leave of more than 6 days. PMID- 1415890 TI - Shoulder strength, power, and endurance in college tennis players. AB - Twenty-four college tennis players were tested for bilateral shoulder internal/external rotation strength on a Cybex 340 isokinetic dynamometer; they were positioned supine with the glenohumeral joint abducted to 90 degrees. Subjects produced significantly (P less than 0.01) more torque in internal rotation at 60 and 300 deg/sec in the dominant arm compared to the nondominant arm. Subjects also produced significantly more power in internal rotation at 60 deg/sec in the dominant arm. No significant differences between the dominant and nondominant arms were seen in internal rotation power at 300 deg/sec or in the internal rotation endurance ratio. No significant differences were seen in external rotation on any measurement. By significantly increasing the strength of the dominant shoulder in internal rotation without subsequent strengthening of the external rotators, muscle imbalances may be created in the dominant arm that could possibly affect the tennis player's predisposition to injuries caused by overloading of the shoulder joint. This study suggests that external rotation strengthening exercises should be implemented in tennis conditioning programs to maintain muscle strength balance, and possibly reduce the chance of overload injury. PMID- 1415889 TI - KT-1000 arthrometer: conscious and unconscious test results using 15, 20, and 30 pounds of force. AB - A recent published report indicated that the reliability and validity of anterior laxity measurements obtained by using the KT-1000 arthrometer were questionable. The purpose of our study was to examine the diagnostic validity of anterior laxity measurements testing patients in conscious and unconscious states using the KT-1000 arthrometer at 15, 20, and 30 pounds of force. The sample included 68 patients with confirmed anterior cruciate ligament disruption. They were given anterior-posterior drawer tests at 20 degrees in both unconscious and conscious states; measurements were recorded at 15, 20, and 30 pounds of force. The results indicated that the measurements in the unconscious state were significantly higher (P less than 0.01) than the values obtained in the conscious state. The anterior cruciate ligament-disrupted knees produced significantly higher (P less than 0.01) anterior laxity. The difference between anterior cruciate ligament disrupted knees and normal knees grew significantly larger (P less than 0.01) as force increased. More patients demonstrated a difference greater than 2 mm between anterior cruciate ligament-disrupted knees and normal knees at 30 pounds (81% to 83%) than at 20 pounds (64% to 72%) of force. Seventy-nine percent of the patients demonstrated a compliance index difference greater than 1 mm using 15 and 30 pounds between the normal and anterior cruciate ligament-disrupted knee. These data provide statistical validity for the compliance index and support for the use of anterior laxity measurements at 30 pounds of force. However, approximately 20% of these patients did not demonstrate an anterior cruciate ligament-disrupted-normal knee difference greater than 2 mm or a compliance index difference of greater than 1 mm. PMID- 1415891 TI - Functional postoperative treatment of Achilles tendon repair. AB - Twenty-one patients with surgically repaired Achilles tendon tears that were treated postoperatively with a functional orthosis rather than routine cast immobilization were evaluated. The orthosis allowed unrestricted plantar flexion and limited dorsiflexion to neutral. Toe-touch weightbearing crutch ambulation was allowed immediately and was gradually increased over the 6 to 8 weeks of treatment. Of the 21 patients, 14 were men and 7 were women; the average age at injury was 35.6 years (range, 19 to 65). The minimum followup was 2 years, with an average of 31 months. The repairs were acute in 18 of the patients and chronic in 3. Subjectively, 16 patients felt they returned to their preinjury level of activity and only 1 was not satisfied with his result. Objectively, there were no significant alterations in ankle range of motion when compared to the contralateral limb, with plantar flexion unchanged and dorsiflexion increased an average of only 2 degrees. The average plantar flexion and dorsiflexion strength, power, and endurance of the ankles as measured by isokinetic testing revealed no significant differences when comparing the operated leg to the nonoperated side: strength, 99% and 93%, respectively; power, 98% and 96%, respectively; and endurance, 93% and 91%, respectively. The angles at which the peak torques occurred were similarly not statistically different. Two patients had superficial wound infections, and 1 had scar adherence of the skin to the tendon. No one had rerupture of the tendon. In conclusion, while the many benefits of postoperative early motion are well proven, there has been hesitation to implement this after Achilles tendon surgery due to the concern of compromising the repair. As shown by this study, early controlled motion can safely and effectively be used following Achilles tendon repair in the motivated, reliable patient. PMID- 1415892 TI - Nontraumatic clavicular osteolysis in weight lifters. AB - In a previous study, we found an overrepresentation of weight lifters in patients who had a resection of the lateral end of the clavicle. To further investigate a possible association between competitive weight lifting and the development of nontraumatic osteolysis of the lateral end of the clavicle, we studied a group of 25 Danish weight lifters. This group was compared to an age-matched control group of 25 men who had never engaged in weight training procedures. None of the subjects had any history of trauma to the shoulder girdle. All 50 subjects underwent radiographic examination of both shoulder joints. In the weight lifter group, seven cases (28%) demonstrated classical radiographic findings of clavicular osteolysis, with loss of subchondral bone detail, translucency, and cystic changes, while four subjects (16%) had subjective symptoms but no radiographic changes. None of the individuals from the control group revealed similar symptoms or radiographic signs. Thus, based on this limited material, the prevalence of the disorder is about 27%. PMID- 1415893 TI - Spontaneous fractures of the humerus during pitching. A series of 12 cases. AB - We report the recent occurrence of spontaneous humeral shaft fractures in 12 pitchers. The subjects were interviewed over the telephone using a standard questionnaire. Radiographs and medical records were solicited from their physicians. Their average age was 36 years and they had pitched an average of 11.4 years with an average layoff of 14 years (range, 7 to 24). Mean time between games pitched was 21 days (range, 3 to 56). The average number of pitches before the fracture occurred was 38 (range, 10 to 100). Pain was experienced at some point before the fracture in 75% of the pitchers and 75% of the fractures were spiral. These fractures were most probably spontaneous fractures brought on by accumulated fatigue damage. The period of buildup after a prolonged period of layoff was probably insufficient time for proper bone remodeling to occur in these men. While a large percentage of these men had pain before their injury, suggesting a predisposing stress fracture, there is no doubt that their fractures could still be caused by a sudden torsional load without the presence of a stress fracture. PMID- 1415894 TI - Quantitative evaluation of knee instability and muscle strength after anterior cruciate ligament reconstruction using patellar and quadriceps tendon. AB - Anterior cruciate ligament reconstruction using an autologous graft harvested from the central one-third of the patellar and quadriceps tendon was performed in 65 knees of 65 patients who were followed from 3 to 7 years. Mean anterior laxity of both knees was measured before and after surgery in each patient using the Styker Knee Laxity Tester. At 30 degrees of knee flexion, 58 patients (89%) had differences of less than 2.5 mm between the operated and unoperated knees. Quadriceps strength was measured with the Cybex II and was less than 50% of the uninjured knee at 3 months after surgery. In men, quadriceps strength returned to 78% of normal at 1 year and 85% at final followup. These values were equal to the preoperative level. In women, the quadriceps strength at final followup was 70%, significantly lower than preoperative strength. Hamstring strength recovered to equal the normal strength. Although anterior cruciate ligament reconstruction using one-third of the patellar and quadriceps tendon achieves stability, postoperative quadriceps weakness is a disadvantage. This weakness may be caused by impairment of the knee extensor mechanism resulting from harvesting the graft. We do not currently recommend this technique for anterior cruciate ligament reconstruction. PMID- 1415895 TI - Acute compartment syndrome of the thigh in sports-related injuries not associated with femoral fractures. PMID- 1415896 TI - Tension pneumarthrosis complicating arthroscopy of the knee. PMID- 1415897 TI - Proximal fibular stress fracture in an aerobic dancer. A case report. PMID- 1415898 TI - Os acromiale in a professional tennis player. PMID- 1415899 TI - A displaced subtrochanteric stress fracture in a young amenorrheic athlete. PMID- 1415900 TI - Association of anabolic steroids and avascular necrosis of femoral heads. PMID- 1415901 TI - Follow-up. PMID- 1415902 TI - Dermatofibrosarcoma protuberans. A clinicopathologic review with emphasis on fibrosarcomatous areas. AB - We reviewed 75 cases of dermatofibrosarcoma protuberans (DFSP) from the University of Texas M.D. Anderson Cancer Center. All accessions were examined for areas of giant cell fibroblastoma (GCF), but none was found. The 30 cases having a minimum of 5 years follow-up were studied in more detail. The histologic findings were typical of DFSP in 24 cases, whereas in six cases discrete areas with a fascicular or "herringbone" growth pattern, considered to represent fibrosarcomatous change (DFSP-FS), were evident. The mitotic rate was usually but not always higher in fibrosarcomatous areas, and occasional examples of typical DFSP demonstrated relatively numerous mitotic figures (up to 35 per 10 high-power fields). Other histologic findings of interest were the presence of melanin in two cases of DFSP and the focal presence of a distinctive type of multinucleated giant cell similar to those seen in GCF in six cases. Patients with DFSP-FS differed from those with DFSP in that they had a higher median age (56 years vs. 37 years). Tumor location was similar in both groups, with the trunk being the most common site. No significant difference in either the rate of local recurrence or the interval until recurrence between DFSP and DFSP-FS was evident; the only factor strongly related to local recurrence was adequacy of surgical margins. However, the only two patients who died of tumor, including the sole patient with distant metastasis, had DFSP-FS. We conclude that DFSP-FS deserves recognition as a variant of DFSP. PMID- 1415903 TI - Muscle differentiation and clinicopathologic features of gastrointestinal stromal tumors. AB - We analyzed 46 gastrointestinal stromal tumors (GISTs) using a panel of antibodies to determine the frequency of smooth muscle differentiation and the relationship of immunophenotype to histopathologic features and clinical behavior. Thirty-six GISTs were classified as benign or malignant based exclusively on clinical behavior; a 2-year minimum follow-up was required for benign lesions. GISTs were immunopositive in the following categories: vimentin 45 of 46, desmin nine of 45, muscle-specific actin (MSA) 36 of 46, alpha-smooth muscle actin (SMA) 34 of 46, chicken gizzard actin-7 zero of 38, cytokeratin two of 46, S100 protein six of 46, glial fibrillary acidic protein (GFAP) zero of 46, synaptophysin zero of 46, and chromogranin one of 46. At least one muscle marker was positive in 39 of 46 tumors. Five GISTs were MSA positive/SMA negative, and three were MSA negative/SMA positive. All desmin-positive cases reacted with MSA or SMA. Eight GISTs were positive for vimentin, MSA, SMA, and desmin, whereas seven were vimentin positive only. Compared with the latter, the former tended to be smaller, less often necrotic, and clinically benign (p less than 0.05 for each). All vimentin-positive only GISTs were malignant. Immunohistochemical features did not correlate with tumor site, cellularity, nuclear pleomorphism, or mitotic rate. Benign GISTs were less cellular than were malignant GISTs (p less than 0.05), but they did not differ statistically in degree of nuclear pleomorphism, necrosis, mitotic rate, or size. We conclude that (a) 85% of GISTs react with at least one muscle antibody; (b) immunohistochemical features are unrelated to anatomic site; (c) SMA is, in effect, as sensitive as MSA, whereas desmin is less sensitive; and (d) simultaneous vimentin, MSA, SMA, and desmin positivity correlates with a benign outcome. PMID- 1415904 TI - Suppurative granulomatous lymphadenitis. Immunohistochemical evidence for a B cell-associated granuloma. AB - The cellular composition of suppurative granulomas was investigated by the application of monoclonal and polyclonal antibodies to paraffin sections and compared with nonsuppurative, hypersensitivity-type granulomas. Macrophages, T cells, and dendritic cells showed a similar distribution in both types of granulomas. In addition to the presence of granulocytes, a major difference between suppurative granulomas and hypersensitive-type granulomas concerned their relationship with B lymphocytes. Hypersensitive-type granulomas were surrounded by small mantle B cells, but they did not contain any B lymphocytes. In contrast, variable numbers of B cells were found either at the periphery or in the center of suppurative granulomas. In view of their morphology (medium size, pale cytoplasm, irregular nuclear shape) and phenotype (L26 +/LN1 -/MB2 +/MT2 +) these B lymphocytes closely resembled monocytoid B cells. The monocytoid B cells might have a role in the recruitment of polymorphonuclear granulocytes and in the development of the necrosis, which occur within suppurative granulomas. PMID- 1415905 TI - Incidental lymphocytic prostatitis. Selective involvement with nonmalignant glands. AB - We documented the presence of lymphocytic prostatitis in all prostate specimens received over a 4-month period. Lymphocytic prostatitis was present in 44% of biopsy specimens (n = 77), 95% of transurethral prostatic resection specimens (n = 20), and 100% of total prostatectomy specimens (n = 9). The patchiness of the prostatitis within the prostate in part explains the lower prevalence in the biopsy specimens, which sample a much smaller portion of the gland compared with the other procedures. Lymphocytic prostatitis was seen in prostates both with and without adenocarcinoma. However, in specimens containing carcinoma, the lymphocytic aggregates rarely involved malignant glands. Instead, the aggregates were either stromal or involved nonmalignant glands either adjacent to or away from the tumor, including glands with hyperplasia, atrophy, and prostatic intraepithelial neoplasia. Even when malignant and nonmalignant glands were in close proximity, there was a sharp demarcation with respect to lymphocytic inflammation. Immunohistochemical staining with B-cell and T-cell markers disclosed that the vast majority are T lymphocytes. The localization of lymphoid aggregates to nonmalignant (including prostatic intraepithelial neoplasia) glands but not frankly neoplastic glands, suggests a selective escape of immune detection by neoplastic glands. PMID- 1415906 TI - Interstitial and airspace granulation tissue reactions in lung transplant recipients. AB - Twenty-three transbronchial and open-lung biopsies from patients who had received a lung allograft displayed fibromyxoid plugs of granulation tissue within airways, airspaces, and the interstitium in a patchy distribution. This granulation tissue-like reaction was identified in three clinicopathologic settings. First, 11 cases occurred with acute lung rejection, of which four cases had been partially treated with steroids for a previous rejection episode. Second, in seven cases the fibromyxoid tissue represented the healing phase of previously diagnosed diffuse alveolar damage resulting from preservation (harvest) injury to the allograft. Third, five cases were related to infection: herpes, Pseudomonas, Serratia, Staphylococcus, and Pneumocystis pneumonias. Although organizing pneumonia-like responses usually suggest an infectious episode, this reaction may be seen as a manifestation of acute lung rejection or ischemic lung injury. PMID- 1415907 TI - Non-Hodgkin's lymphomas arising in patients successfully treated for Hodgkin's disease. A clinical, histologic, and immunophenotypic study of 14 cases. AB - We report on 14 patients who developed Hodgkin's disease (HD), were successfully treated, and subsequently developed non-Hodgkin's lymphoma (NHL). The median interval between the diagnosis of HD and the diagnosis of NHL was 136 months (range 11-336). The clinical features of the patients with HD were similar to other patients with HD. Results of biopsies showed 12 nodular sclerosis and one mixed cellularity; one was not further classified. Immunophenotypic studies in nine cases showed that the Reed-Sternberg (RS) and Hodgkin's (H) cells were LeuM1+ LCA-. The patients were treated for HD in a nonuniform manner: two received radiation therapy, four received chemotherapy, and eight received both modalities. The NHLs were usually extranodal (79%) with frequent presentation as an abdominal mass. According to the Working Formulation, six lymphomas were small noncleaved cell (four non-Burkitt's, two Burkitt's), three were diffuse large cell, and two were follicular and diffuse large cell. Three neoplasms were not classified: two lymphomas with plasmacytoid differentiation were placed in the intermediate and low-grade categories, respectively, and one neoplasm was a plasmacytoma. All 14 neoplasms had an immunophenotype typical of NHL of B-cell lineage and were LeuM1-. Seven of the 12 patients treated with combination chemotherapy experienced a complete remission of their NHL. We conclude that the clinical, histologic, and immunophenotypic findings of the NHLs in these patients are analogous to those of NHLs that occur in immunosuppressed patients, suggesting that immunodeficiency plays a role in the pathogenesis of NHLs arising after HD. PMID- 1415908 TI - Inflammatory pseudotumors of the major salivary glands. Clinicopathologic and immunohistochemical analysis of six cases. AB - Inflammatory pseudotumor is a pathologic term used to describe reactive, pseudoneoplastic phenomena, which reportedly occur in many parts of the body. Clinicopathologic and immunohistochemical findings in six cases of inflammatory pseudotumor of the major salivary glands are described. All six lesions involved the parotid gland. There were three men and three women affected, with a median age of 72.5 years. All patients presented with a swelling of several months' duration in the parotid region. Five patients were alive and free of tumor at an average of 3.2 years after surgical removal, and one patient was lost to follow up. The lesions were firm, discrete nodules, grossly described as homogenous yellow-gray tissue. Histologically, all lesions contained a diversified admixture of four histological elements: (a) myofibroblasts, (b) histiocytes, (c) plasma cells, and (d) lymphocytes. Results of immunohistochemical studies showed a biphasic spindle cell population of myofibroblasts and histiocytes with variable staining characteristics for KP-1(CD-3), smooth muscle actin, muscle-specific actin, and vimentin. These findings are in agreement with the concept that inflammatory pseudotumor is a fibroinflammatory lesion with an abundant component of myofibroblastic/fibrohistiocytic elements. PMID- 1415909 TI - Low-grade mucinous cystadenocarcinoma in the spleen. AB - A 69-year-old man with an enlarged spleen, found by computed tomography scan to be multicystic, underwent a splenectomy. Pathological examination revealed a Low grade mucinous cystadenocarcinoma that was histologically analogous to a mucinous tumor of the ovary. The serum level of tumor markers carcinoembryonic antigen (CEA)and CA19-9 were elevated preoperatively and returned to normal after the operation. In the absence of a primary tumor elsewhere, we considered this tumor to be primary in the spleen, and it was presumed that the tumor arose either from invaginated capsular mesothelium of the spleen or from heterotopic pancreatic or enteric tissue within the spleen. PMID- 1415910 TI - The Bethesda System for reporting cervical/vaginal cytologic diagnoses. Report of the 1991 Bethesda Workshop. PMID- 1415911 TI - Atypical duct hyperplasia in young females. PMID- 1415912 TI - Program and abstracts of the 41st annual meeting of the American Society of Tropical Medicine and Hygiene. Seattle, Washington, November 15-19, 1992. PMID- 1415913 TI - The vascular laboratory: the past and the future. PMID- 1415914 TI - New evidence and new hope concerning endothelial seeding of vascular grafts. AB - Endothelial cell (EC) seeding of prosthetic bypass grafts has been promoted as a method of improving graft patency. However, an efficient and reliable method of seeding vascular prostheses with ECs is lacking due to inefficient harvesting of ECs and poor attachment and proliferation of cells on the prosthetic surfaces. To investigate the effect of a commonly used prosthetic surface on EC attachment and proliferation, we measured the attachment and proliferation of ECs on polytetrafluoroethylene (PTFE) grafts uncoated or coated with gelatin, laminin, fibronectin, collagen type I and/or III, or RGD (arginine-glycine-aspartate) containing peptide. EC attachment and proliferation were both significantly decreased on the untreated PTFE graft surface. Conversely, coating of PTFE with fibronectin, RGD, laminin, or gelatin significantly (p less than 0.05) improved the attachment of ECs, with the most striking increases occurring with laminin and gelatin. Similarly, all matrix components in this study improved EC proliferation compared with untreated PTFE, with RGD and gelatin producing the most significant improvement. PTFE adversely effects EC attachment and proliferation. These properties can be improved by treating PTFE graft surfaces with extracellular matrix components in relatively low concentrations. Future investigations are needed to determine whether there are combinations and concentrations of matrix components that will optimize these cellular functions on vascular prostheses. PMID- 1415915 TI - Influence of arterial access sites and interventional procedures on vascular complications after cardiac catheterizations. AB - The purpose of this study is to define the incidence of complications at the arterial access site after cardiac catheterization. The influence of the arterial access site on these complications was identified, as were the clinical characteristics of these problems. A total of 8,797 cardiac catheterizations were performed over the 3-year period of this study. Diagnostic catheterizations and percutaneous transluminal coronary angioplasties (PTCAs) were included, and the arterial access site was identified. Diagnostic catheterizations were performed via the brachial artery (group I, n = 3,137) or the femoral artery (group II, n = 4,055). PTCAs were also performed via the brachial artery (group III, n = 32) or the femoral route (group IV, n = 1,573). Ninety-five major vascular complications occurred during the course of this study. The frequency of complications was higher with brachial artery catheterization when compared with the femoral route. PTCA was associated with a higher complication rate than diagnostic studies. Brachial artery complications were primarily arterial thromboses, which were easily diagnosed and treated. Femoral artery complications were more complicated, difficult to identify, and associated with significant morbidity. PMID- 1415916 TI - Risk of spinal cord dysfunction in patients undergoing thoracoabdominal aortic replacement. AB - The records of 150 consecutive patients undergoing thoracoabdominal aortic replacement from 1980 to 1991 were retrospectively reviewed. There were 89 men and 61 women; mean age was 67.8 years (range: 33 to 88 years). Since June 1989, a multimodality prospective perioperative protocol was used to reduce the risk of spinal cord dysfunction. Ischemia is minimized by complete intercostal reimplantation whenever possible, cerebrospinal fluid drainage, and maintenance of proximal hypertension during cross-clamping. Spinal cord metabolism is reduced by moderate hypothermia, high-dose barbiturates, and avoidance of hyperglycemia. Reperfusion injury is minimized by the use of mannitol, steroids, and calcium channel blockers. Ninety-seven percent of patients survived long enough for evaluation of their neurologic function. Spinal cord dysfunction was reduced from 6 of 108 (6%) in the preprotocol group to 0 of 42 in the protocol group (0%) (p less than 0.01). The overall 30-day operative mortality was not significantly different between the groups (9% versus 12%, p = NS). A multimodality protocol appears to be effective in reducing the risk of spinal cord injury during thoracoabdominal aortic replacement. PMID- 1415917 TI - Nonoperative management of visceral aneurysms and pseudoaneurysms. AB - During the period from 1975 to 1991, 41 patients with 60 visceral artery aneurysms were treated at the Affiliated Hospitals of Emory University. The total included 13 patients in whom 16 aneurysms were treated primarily by transarterial embolization. There were seven hepatic artery aneurysms, three splenic artery aneurysms, three gastroduodenal artery aneurysms, two left gastric artery aneurysms, and one right gastroepiploic artery aneurysm. Average age of these patients was 50 years; there were eight males and five females. Seven patients presented with gastrointestinal bleeding, and two patients presented with abdominal pain. In four patients, the aneurysm was an incidental finding. Etiology of the true or false aneurysms consisted of pancreatitis in two patients, trauma in three patients, connective tissue disease in one, and was unknown in the remainder. Embolization was performed in seven cases with Gianturco coils and Gelfoam, with coils alone in four, with Gelfoam alone in four, and with detachable balloons in one instance. Complete occlusion was achieved initially in 13 cases. Recanalization occurred in two patients over a mean follow-up period of 8.6 months, requiring re-embolization in one patient, whereas the other patient was managed expectantly. In three cases, embolization was unsuccessful: two cases required surgical correction, and one case was managed expectantly. Only one complication was related to the embolization procedure, which was a common hepatic arterial dissection that proceeded to the formation of a false aneurysm. Embolization as the primary treatment modality for visceral artery aneurysms should be considered in patients with the following diagnoses: pseudoaneurysms associated with pancreatitis, intrahepatic aneurysms, most splenic artery aneurysms, and gastric, gastroduodenal, and gastroepiploic aneurysms. The procedure has a low risk and may obviate a difficult surgical procedure, but it does not preclude surgical intervention should the need arise. PMID- 1415918 TI - Influence of complete revascularization on chronic mesenteric ischemia. AB - Complete revascularization for chronic intestinal ischemia is controversial. Fifty-eight patients (119 arteries) underwent mesenteric revascularization between 1981 and 1988. There were 46 women and 12 men (mean age: 63 years). Sixty percent of patients had three-vessel disease. Twenty-one patients underwent concomitant aortic reconstruction. Operative mortality was 10%. Four of the six deaths occurred in patients undergoing aortic surgery. Late graft failure occurred in five patients (10%). Five-year survival for patients with three vessel involvement who underwent three-vessel repair was 73%, compared with 57% for two-vessel repair and 0% for one-vessel repair (p = NS). Similarly, graft patency in patients with three-vessel disease was highest in those patients who had complete revascularization (90%, 54%, and 0%, respectively) (p = NS). We conclude that increased graft patency and survival in patients with three-vessel disease was most frequent with complete revascularization. Diseased inferior mesenteric arteries should be repaired if feasible. Concomitant aortic operations should be avoided if possible. PMID- 1415919 TI - Long-term follow-up of poor-risk patients undergoing small-diameter portacaval shunts. AB - The small-diameter portacaval H-graft has been shown to be a reliable method of controlling variceal hemorrhage. However, little has been written about the long term follow-up of poor-risk patients treated by this method. Over the last 11 years, we have performed 38 portacaval H-grafts; 79% of the patients were Child's B or C, and 79% were alcoholic. The mean age was 52 years, and the mean period of follow-up was 44 months. Over 37% of the grafts were performed in patients who were bleeding at the time of operation. Our 30-day operative mortality was 13%. Postoperatively, the small-diameter H-graft was associated with mild to moderate encephalopathy in 33% of the patients and ascites in 42%. Both these conditions were easily controlled with diet and medication. Early recurrent variceal bleeding was seen in 13% of patients. However, on late follow-up, recurrent hemorrhage and encephalopathy have been seen in only 12% and 14% of patients, respectively. We conclude that the portacaval H-graft is a reliable and lasting method for controlling variceal bleeding with an acceptable postoperative morbidity and mortality. PMID- 1415921 TI - Safety of arteriography by direct puncture of a vascular prosthesis. AB - A total of 122 catheterizations were performed in 105 patients with femoral grafts. Ninety-five femoral grafts were punctured. The mean follow-up time was 21 months. Sixty-one patients had follow-up duplex ultrasounds of the graft puncture site at 6 months. The complication rates for patients with direct graft puncture were comparable to those of patients without grafts undergoing femoral catheter arteriography. Twenty-seven cases with femoral grafts had arteriography using the transaxillary technique. The overall complication rate for the 95 cases with graft puncture was 12% (8% were minor complications) in contrast to 30% (22% were major complications) for the 27 cases with the transaxillary approach. The local, nervous system, and major complication rates were all significantly less in patients with graft puncture than in patients with the transaxillary approach. There was no evidence of early or late pseudoaneurysm formation, disruption of the suture line, or late graft infection in patients with graft puncture. Direct graft puncture arteriography is safe and preferable to the transaxillary approach. PMID- 1415920 TI - Major complications of angioaccess surgery. AB - Angioaccess procedures at one institution over a 4-year period were retrospectively reviewed to ascertain the frequency of major limb- or life threatening complications. A total of 435 angioaccess procedures were performed, including 81 Cimino-Brescia fistulas, 166 polytetrafluoroethylene grafts, and 111 thrombectomy/revisions. There were 77 operations for major complications in 53 patients. In addition, five patients required major vascular repair or emergency thoracotomy for complications of central hemodialysis line placement. A significant portion (18% of this series) of the total angioaccess caseload of a vascular surgeon will be utilized in the repair of major complications. The in hospital (6 patients, or 11%) and long-term (12 patients, or 23%) mortality rates are significant. Although most complications can be repaired without limb loss and with shunt salvage, a small percentage (in our study three patients, or 4%) will have debilitating long-term symptoms. PMID- 1415922 TI - Arterial and ischemic aspects of total knee arthroplasty. AB - Prospective and retrospective analyses of 1,182 consecutive patients undergoing primary total knee arthroplasty (TKA) were performed to determine (1) the incidence of chronic lower extremity ischemia (CLEI); (2) the effect of tourniquet occlusion; and (3) guidelines that will allow TKA to be performed safely. Despite the appropriately advanced age of our patients, the incidence of CLEI was only 2%. All ischemic complications occurred in six patients with CLEI (25%), but none resulted in death or amputation. The ischemic complications consisted of pressure-induced necrosis of toes, heel, or foot, atheroembolism, femoral-popliteal graft occlusion, and asymptomatic popliteal occlusion. Tourniquet compression in the 1,158 patients without CLEI produced no untoward effects. Patients with mild CLEI can have a TKA performed safely with a tourniquet if there is no femoropopliteal calcification. When the ischemia is severe or there is a femoropopliteal aneurysm, arterial reconstruction should precede the TKA. In patients with patent femoral-popliteal bypasses or calcification without ischemia, TKA should be performed without a tourniquet. Ischemic pressure necrosis is an additional mechanism of injury. PMID- 1415923 TI - Thrombolytic therapy of synthetic graft occlusions before vascular reconstructive procedures. AB - The objective of this study was to evaluate the impact of thrombolysis of synthetic grafts before urgent vascular reconstruction. In 29 patients, 41 thrombosed synthetic grafts that underwent intraarterial thrombolysis were studied. The cases were divided into three groups: group I--complete thrombolysis followed by reconstruction; group II--complete thrombolysis alone; and group III- incomplete lysis requiring reconstruction or sympathectomy. Follow-up ranged from 1 to 556 days (mean: 149 days). Kaplan-Meier analysis was used to determine patency and limb salvage rates. One-year patency and limb salvage rates were 53% and 95%, 34% and 67%, and 38% and 48%, respectively, for groups I, II, and III. Eighteen complications occurred in 16 of the 41 (39%) episodes. One patient died of intracranial hemorrhage. The best results were achieved when complete lysis was followed by appropriate reconstruction. Patency was equally poor in complete thrombolysis alone and reconstructions required by incomplete thrombolysis. Limb salvage was better after complete thrombolysis, regardless of the appropriate reconstruction. PMID- 1415924 TI - Liver and spleen phagocytic depression after peripheral ischemia and reperfusion. AB - Liver and spleen phagocytic clearance of blood-borne microparticulate tissue debris and products of intravascular coagulation after trauma and surgical injury is an important mechanism to limit the deposition of debris in the pulmonary vascular bed. Plasma fibronectin (pFn) modulates this clearance process. We evaluated the effect of a localized peripheral ischemia and reperfusion injury on liver and spleen phagocytic function. Male rats (250 to 350 g) underwent 4 hours of tourniquet-induced bilateral hindlimb ischemia, followed by 18 hours of reperfusion after release of the tourniquet. Rats subjected to ether anesthesia alone or anesthesia followed by groin incision without ischemia were the control and sham groups, respectively. Reticuloendothelial (RE) phagocytic function was assessed at 15 minutes and 18 hours after the start of reperfusion by the in vivo liver and spleen removal of blood-borne iodine 125 (125I)-test microparticles, which were coated with gelatin (denatured collagen) to enhance their interaction with pFn. Liver and spleen particle uptake in control and sham rats was similar. In contrast, after 4 hours of ischemic injury with 15 minutes of reperfusion, we observed a 30% to 40% decrease (p less than 0.05) in liver and spleen particle uptake as compared with sham controls with partial restoration of this removal mechanism by 18 hours. This depression in liver and spleen phagocytic function was associated with a significant (p less than 0.05) increase in the deposition of the 125I-test particles in the lung. RE depression was not due to a deficiency of pFn; indeed, a marked elevation (588 +/- 12 micrograms/mL versus 1,083 +/- 40 micrograms/mL) of pFn was observed by immunoassay over the 18-hour reperfusion interval. Comparative bioassay of humoral (opsonic) versus cellular (Kupffer's cell) activity revealed that Kupffer's cells in livers from controls or ischemia reperfusion rats exhibited normal phagocytic function when incubated in plasma harvested from either control or 4-hour ischemic rats. The opsonic activity of plasma harvested after ischemia and reperfusion was also more than adequate, consistent with the immunoassay analysis. Thus, the impaired liver and spleen clearance mechanism after peripheral ischemia and reperfusion injury did not appear to be due to either a macrophage cellular deficit or a lack of pFn. This clearance depression may be mediated by splanchnic malperfusion, which is known to develop after peripheral ischemia and reperfusion and associated soft tissue injury. PMID- 1415926 TI - Physiologic similarities between extremities with varicose veins and with chronic venous insufficiency utilizing air plethysmography. AB - Air plethysmography (APG) was used to measure maximal venous outflow rate (MVO), a test for proximal venous obstruction; venous volume; venous filling index, an estimate of valvular incompetence; ejection fraction (EF), a test of calf-muscle pump efficiency; and residual volume fraction (RVF), an estimate of ambulatory venous pressure. MVO was lower in patients with chronic venous insufficiency (CVI) than in those with varicose veins (VV), but the difference was small (p = 0.06). RVF was significantly greater in extremities with CVI when compared with those with VV (p less than 0.01). However, the degree of abnormality in venous volume, venous filling index, and EF was similar in CVI and VV extremities. In summary, although RVF tends to be higher in extremities with CVI when compared with those with VV, there is tremendous overlap between VV and CVI for each of the hemodynamic variables measured by APG. Therefore, the pathophysiology of CVI is likely to involve not only hemodynamic abnormalities but also other factors that have not yet been clearly identified. PMID- 1415925 TI - Prospective comparison of duplex scanning and descending venography in the assessment of venous insufficiency. AB - A prospective study comparing duplex scanning and descending venography was applied to 143 venous segments in 25 extremities with moderate to severe manifestations of chronic venous insufficiency (class 2 or 3). Duplex scanning was performed with the patient in the 15 degree reverse Trendelenburg position, and descending venography with the patient in the 60 degrees semi-erect position; the Valsalva maneuver was used to elicit reflux in both tests. The duplex parameter of reflux duration greater than 0.5 second correlated with venographic reflux in 94 of 105 segments (sensitivity of 90%). Conversely, reflux time less than or equal to 0.5 second correlated with venographic competence in 32 of 38 segments (specificity of 84%). A total of 17 discrepancies were identified among the 143 total segments studied, for an accuracy of 88%. The largest proportion of discrepancies was identified in the group with venographic competence and reflux duration greater than 0.5 second and less than or equal to 2.0 seconds; this was designated a gray zone. Mean peak velocities were significantly higher in the reflux group when compared with the competence group in the profunda femoris vein (p = 0.047), greater saphenous vein (p less than 0.001), popliteal vein (p less than 0.001), and tibial vein (p = 0.005). We conclude that venographic reflux correlates best with duplex scan findings of reflux duration greater than 0.5 second. Duration of reflux greater than 0.5 second and less than or equal to 2.0 seconds, however, represents a gray zone and should be interpreted with caution since this could lead to over-reading of reflux disease, in which case verification of incompetence by descending venography may be indicated. PMID- 1415927 TI - Why does prophylaxis with external pneumatic compression for deep vein thrombosis fail? AB - External pneumatic compression (EPC) devices are increasing in popularity for deep vein thrombosis (DVT) prophylaxis. Patients who have these devices applied postoperatively are assumed to have effective prophylaxis, although a number of extensive postoperative DVT complications have been observed. This study evaluates the proper application of EPC devices in patients in intensive care units and regular nursing floor units and assesses whether dedicated in-service instruction can improve proper use. In a prospective study of 138 patients with 2 or more risk factors for postoperative DVT, it was found that patients on routine nursing units had properly functioning EPC devices during 48% (306 of 636) of the visits compared with 78% (312 of 398) of the visits in the intensive care unit (ICU) (p less than 0.0001). Follow-up of patients transferred from an ICU to a regular nursing unit showed that functional application decreased from 82% (129 of 157) to 33% (40 of 122) (p less than 0.005). The compression sleeves were not applied in 84% of the nonfunctional devices and were properly in place but the pump nonfunctional in 16%. Unfortunately, dedicated in-service instruction did not improve the proper use of EPC. Although proper application of EPC is better in the ICU compared with regular nursing units, improper use is frequent and failure of DVT prophylaxis with EPC devices may be due to improper use, rather than failure of the method itself. PMID- 1415928 TI - Operative management of greater saphenous thrombophlebitis involving the saphenofemoral junction. AB - Forty-three consecutive patients with greater saphenous vein (GSV) thrombosis extending to the saphenofemoral junction (SFJ) were treated. Twenty-three patients had extension of thrombus into the common femoral vein (CFV). Twenty patients had thrombus extending to but not within the CFV. Symptoms, risk factors, and physical examination were not predictive of CFV thrombus extension. When compared with the operative record, duplex scans accurately located the extent of the thrombosis 100% of the time. Forty-one surgical procedures were performed. No patients had pulmonary emboli during the procedures. Thirty-seven patients were treated as outpatients or were discharged within 3 days of their surgical procedures. The two patients who did not undergo operative procedures in this series had complete occlusion of the CFV with extension into the external iliac vein. Thrombus within 3 cm of the SFJ is an indication for surgical intervention. Disconnection of the GSV from the CFV prevents extension of the thrombus, and a limited CFV thrombectomy can be performed when necessary. This is considerably more cost-effective than treatment with anticoagulation. PMID- 1415929 TI - Are there angiographic predictors of success for vein bypass to the peroneal artery? AB - In order to evaluate the effect of angiographic run-off upon peroneal artery autogenous vein bypass patency and subsequent limb salvage, 53 autogenous vein peroneal artery bypasses performed for ischemic tissue loss were reviewed. All preoperative angiograms were evaluated according to three separate angiographic scoring systems that previously had been designed to quantify the severity of runoff resistance. None of the three scoring systems predicted either early bypass occlusion and/or major amputation. The cumulative 18-month primary patency and 24-month secondary patency rates were 71% and 90%, respectively. The 24-month limb salvage rate was 81%. Initial and intermediate-term salvage of limbs with ischemic tissue loss can be achieved by peroneal artery bypass. Angiographic scoring systems were poor predictors of bypass failure or major amputation. PMID- 1415930 TI - Clinical and hemodynamic results of bypass to isolated tibial artery segments for ischemic ulceration of the foot. AB - Patients with ischemic ulceration of the foot and no continuous tibial or inframalleolar vessels acceptable for bypass are often treated with primary amputation. We have performed autogenous vein bypass to isolated tibial artery segments (ITAS) in nine patients with ischemic foot ulcers and no other outflow options. We reviewed the clinical and hemodynamic results of these bypasses to assess the efficacy of this approach. Hemodynamic comparisons of these ITAS bypasses were made to a concurrent series of 26 bypasses to intact tibial arteries and 24 inframalleolar artery bypasses assessed during routine follow-up. Eight of the bypasses originated from the above-knee popliteal artery and one from the profunda femoris artery. Recipient vessels were the anterior tibial (seven), peroneal (one), and posterior tibial (one) arteries. Although mean ankle brachial indices (ABI) increased significantly from 0.26 +/- 0.06 preoperatively to 0.75 +/- 0.04 postoperatively (p = 0.0015), ITAS bypass patients had lower mean postoperative ABIs than patients with bypasses to intact tibial (ABI = 0.98 +/- 0.03, p = 0.0001) or pedal arteries (ABI = 1.02 +/- 0.04, p = 0.0005). Similarly, duplex scan-derived peak systolic flow velocities of the ITAS bypasses (mean: 52.9 +/- 5.8 cm/sec) were lower than those of intact tibial artery bypasses (mean: 80.1 +/- 6.1 cm/sec, p = 0.02) but did not differ from those of pedal bypasses (mean: 59.5 +/- 3.5 cm/sec, p = 0.34). No ITAS bypass grafts have failed during a mean follow-up of 12.3 +/- 2.7 months. Although wound healing was prolonged (mean: 3.1 +/- 0.6 months), the wounds of eight of nine patients eventually healed, with three patients requiring minor amputations (one digital amputation and two transmetatarsal amputations). Although the hemodynamic results of ITAS bypass are inferior to those of more conventional bypasses, the early patency rates and successful healing of ischemic wounds confirm that it is a valid alternative in the threatened limb with no other outflow options. PMID- 1415931 TI - Clinical results of decompressive dermotomy-fasciotomy. AB - Seventy-three dermotomy-fasciotomies (DFs) were performed in 68 patients from 1986 to 1991. A database record was compiled on each patient. Variables included age, mode of injury, method of initial wound closure, and associated injuries. A multivariate stepwise logistic regression analysis was performed to determine which variables were associated with wound complications. Thirty-eight percent of patients who underwent DF developed wound complications. One hundred percent of those patients with postoperative arterial or graft thrombosis developed wound complications (p less than 0.01) as did 78% of those with thromboembolic disease (p less than 0.05). Conversely, only 5% of those who underwent closure of their DF wounds utilizing skin grafts developed wound complications (p less than 0.01) as compared with 51% of those who underwent secondary or primary closure only. Subsequent analysis of the remaining patients, excluding those with severe soft tissue injury, showed an association between location of DF (upper versus lower extremity) and the development of wound complications that approached statistical significance (p less than 0.06). DF is frequently necessary in the treatment of patients with compartment syndrome but is associated with significant morbidity. This study suggests that closure of DF wounds utilizing skin graft allows for continued osteofascial decompression while concomitantly minimizing invasive sepsis. PMID- 1415932 TI - Management of infected lower extremity autologous vein grafts by selective graft preservation. AB - Between 1975 and 1991, we treated 16 patients with infected lower extremity autologous vein grafts performed for limb salvage by complete graft preservation. Traditional treatment of these infections includes immediate graft excision and complex revascularization procedures to prevent limb loss. The infection involved an intact anastomosis in 12 patients or the body of a patent graft in 4 patients. None of the patients was systemically septic. All patients were treated with appropriate intravenous antibiotics. Six patients were treated by placement of autologous tissue on the exposed graft (4 rotational muscle flaps, 2 skin grafts), and 10 were treated with antibiotic-soaked dressing changes and repeated operative debridements to achieve delayed secondary wound healing. This treatment resulted in a 19% (3 of 16) mortality rate and an 8% (1 of 13) amputation rate in survivors. Of the six patients managed by autologous tissue placement onto the infected graft, five patients had wounds that healed without complications, and one died of a myocardial infarction. Of the 10 patients treated by delayed secondary wound healing, 2 developed anastomotic hemorrhage, which resulted in death in 1 patient and above-knee amputation in the other, 1 died of a myocardial infarction, 1 developed graft thrombosis, and 6 had wounds that healed. Placement of autologous tissue to cover an exposed, infected patent vein graft with intact anastomoses may prevent graft dessication, disruption, and thrombosis, which renders graft preservation an easier, safer method of treatment compared with routine graft excision. PMID- 1415933 TI - Donor iliac angioplasty and crossover femorofemoral bypass. AB - We reviewed our experience with 99 patients who had 111 femorofemoral bypass grafts placed over a 10-year period. Mean follow-up was 36 +/- 28 months (range: 1 to 120 months). Bypass alone was performed in 89 cases (group 1). Preoperative donor iliac angioplasty was utilized in 22 cases (group 2). Overall graft failure was 21 of 89 in group 1 and 2 of 22 in group 2 (difference was not significant by chi 2: p greater than 0.05). Clinical success as calculated by life-table analysis was 95%, 83%, 75%, and 67% at 1, 3, 5, and 7 years, respectively, for group 1. Clinical success was 100% and 91% at 1 and 3 years, respectively, and 91% at 42 months for group 2. The success rates were not different for the two groups when analyzed by the log-rank test at 42 months (p greater than 0.30). We conclude that donor iliac angioplasty and femorofemoral bypass is an excellent option for patients with severe occlusive disease of one iliac artery and contralateral disease amenable to angioplasty. PMID- 1415934 TI - Diagnostic and prognostic molecular markers in cancer. PMID- 1415935 TI - Summary of Pancreas Club meeting. May 9, 1992 San Francisco, California. PMID- 1415936 TI - Management of small artery vascular trauma. AB - This 11-year retrospective study reviewed 99 arterial injuries distal to the brachial bifurcation or popliteal trifurcation in 89 extremities in 88 patients. Associated injuries occurred in 78 of 88 (89%) patients, including 10 fractures or dislocations, 66 nerve injuries, and 59 single or multiple tendon injuries. Fasciotomy was performed in 9 upper extremities and 11 lower extremities (23% of patients). The selection of operative treatment by arterial repair or ligation was by surgeon choice (52% repair and 48% ligation). Postoperative patency was found in 45 of 47 (96%) repaired arteries. In cases of isolated single arterial injuries (10), there were excellent results, and there was no difference in the results between repair and ligation. In cases of nonisolated single arterial injuries (69), there were 46% and 36% nonvascular complications in the repaired and ligated groups, respectively. In 10 patients with nonisolated multiple arterial injuries in the same extremity, the results of repair of one artery with ligation of the other artery versus repair of both arteries were identical, and there were no vascular complications. Operative exploration was the key to complete evaluation of vascular and neuro/musculoskeletal injuries. The data suggest that one functional artery distal to the elbow or knee is sufficient for limb viability and vascular function (follow-up range: 0 to 110 months; mean: 12 months). Nerve injury was the single most important factor of extremity injury in terms of the degree of functional loss. PMID- 1415937 TI - Lower-extremity amputation with immediate postoperative prosthetic placement. AB - To study the efficacy of an immediate postoperative prosthesis (IPOP) program, a retrospective review of 167 major lower-extremity amputations was performed. Patient enrollment in the IPOP program was based on the individual's potential for rehabilitation and participation in an aggressive postoperative physical therapy regimen, as determined by the surgeon, prosthetist, physical therapist, and social worker. Indications for amputation were intractable infection and/or severe unreconstructable arterial insufficiency. Sixty-five patients underwent 69 amputations with IPOP (59 below knee; 10 above knee). Successful program completion was defined as independent ambulation and occurred in 86% of those patients enrolled. The average interval from amputation to ambulation was 15.2 days for the below-knee amputees and 9.3 days for the above-knee amputees. Failure to complete the program occurred in 14% of patients and was due to noncompliance, stump infection, stump trauma, and death. The results of this review support the use of IPOP after major lower-extremity amputation. PMID- 1415938 TI - Gastric antroplasty for the treatment of delayed gastric emptying and gastroesophageal reflux in children. AB - Operative correction of symptomatic gastroesophageal reflux (GER) was undertaken in 530 children during a 21-year period. Gastroesophageal fundoplication (GEF) alone was performed in 415 children; 83 had simultaneous GEF and pyloroplasty; 13 had pyloroplasty alone; and 19 had GEF with later pyloroplasty. Of the last 355 children with reflux, 110 (31%) had pyloroplasty. Pyloroplasty was performed for persistent symptoms despite medical therapy when more than 60% of the isotope meal was retained in the stomach at 90 minutes. Children with central nervous system disorders and GER often had delayed gastric emptying (DGE). A modified Heineke-Mikulicz pyloroplasty was used for the first 59 children; the last 56 patients had a more simplified antroplasty with a 2.5- to 3.5-cm vertical incision through the antral muscularis down to the duodenum without mucosal incision; the muscularis was reapproximated in a transverse direction with sutures. With a mean follow-up of 5.8 years, only three patients experienced mild transient dumping. None had pyloroplasty leak or clinical evidence of alkaline reflux. Antroplasty is a helpful, simple adjunct to GEF with low morbidity in children with GER and DGE. PMID- 1415939 TI - Nissen fundoplication in the treatment of children with familial dysautonomia. AB - Thirty-four children with familial dysautonomia (FD) underwent Nissen fundoplication and gastrostomy. The indications for operation were persistent cyclic vomiting that resulted in repeated aspiration pneumonia (94% of the patients), chronic dehydration (82%), failure to thrive (97%), and frequent hospitalizations (76%). There was no operative or early postoperative mortality. Long-term follow-up for up to 12 years was available. Eight patients died during this period from 7 months to 7.5 years postoperatively. In 5 patients (15% of the operated patients), the fundoplication ceased to function 16 months to 5 years postoperatively, which was attributed mainly to repeated severe dysautonomic crises with vigorous retching. Vomiting ceased in 85% of the symptomatic patients; pulmonary deterioration was halted, and the frequency of aspiration pneumonia was reduced in 68%; nutritional improvement was seen in 44%; the hydration status improved in 88%; and the frequency of hospital admissions decreased in 74%. These long-term findings resulted in a significant improvement in the quality of life for the majority of the patients. The absence of operative mortality and the low postoperative morbidity, together with the long-term beneficial results of this surgical procedure, should encourage early surgical intervention in selected FD patients. PMID- 1415940 TI - Further evidence against the routine use of parathyroid ultrasonography prior to initial neck exploration for hyperparathyroidism. AB - The role of preoperative localization tests in patients undergoing initial neck exploration for hyperparathyroidism (HPT) is controversial. The use of parathyroid ultrasonography (US) in 46 patients (7 men, 39 women; mean age: 60 years) who underwent initial neck exploration for hypercalcemia and who had the diagnosis of HPT confirmed at surgery is reported. At surgery, a single adenoma was found in 40 patients and multiple hyperplastic glands in 6 patients. Of the 40 adenomas, only 22 (58%) were localized to the correct side by the preoperative US, and only 5 of 18 hyperplastic glands (28%) were correctly localized. The rates of false-positive and false-negative results were 10% and 46%, respectively. The sensitivity of parathyroid US was 54%, the specificity 90%, and the accuracy 70%. The low sensitivity and accuracy and the high rate of false negative test results that were observed suggest that there is no role for the routine use of parathyroid US in patients undergoing initial neck exploration for HPT. PMID- 1415941 TI - Lipocortin-present perforating and lipocortin-absent nonperforating Crohn's disease. AB - To investigate whether Crohn's disease has two different clinical forms, a relatively aggressive perforating type and a more indolent nonperforating type, we compared the concentrations of lipocortin and prostaglandin E2 (PGE2) in the inflamed mucosa of 12 patients with strictly controlled Crohn's disease with those found in histologically normal mucosa of control subjects. The inflamed mucosa obtained from eight patients with nonperforating Crohn's disease did not react with antilipocortin antibody on immune blot analysis. In contrast, the inflamed mucosa from four patients with perforating Crohn's disease, as well as that obtained from histologically normal controls, contained lipocortins. In addition, higher concentrations of intramucosal ileal and colonic PGE2 were found in patients with nonperforating Crohn's disease (902 +/- 454 pg/wet weight [WW] mg and 1,268 +/- 567 pg/WW mg, respectively) compared with normal controls (90.2 +/- 43.1 pg/WW mg and 173 +/- 76.5 pg/WW mg, respectively) (p less than 0.01). The difference in intramucosal ileal and colonic PGE2 levels between patients with perforating Crohn's disease (109.6 +/- 16.7 pg/WW mg and 252 +/- 34.4 pg/WW mg, respectively) and normal controls was not significant. These findings indicate that there may be two distinct patterns of Crohn's disease that differ in the amount of lipocortin present in the intestinal mucosa. PMID- 1415942 TI - Long-term follow-up of partial splenectomy in Gaucher's disease. AB - Seven children with Gaucher's disease who underwent partial splenectomy were followed for 7 to 8 years. None of the children had systemic sepsis or symptoms related to liver enlargement. Bone crisis occurred in only two children who had experienced bone crisis prior to partial splenectomy. This contrasts with the development of bone crises in five of six children who underwent total splenectomy at a similar age and who had previously been free of bone symptoms. Partial splenectomy should be regarded as a temporary solution in the treatment of hypersplenism and the mechanical compression related to the huge spleen. In 71% of the patients, massive enlargement and a severe to moderate degree of pancytopenia occurred again after 3 to 8 years; total splenectomy was required in three patients. PMID- 1415943 TI - Collagen synthetic capacity throughout the uninjured and anastomosed intestinal wall. AB - The capacity to synthesize collagen was measured throughout the intestinal tract of the rat, using an in vitro technique. In addition, the effect of anastomotic construction in either the ileum or the colon on collagen synthetic capacity at specific distant locations both 1 and 4 days after operation was investigated. Collagen synthetic capacity is relatively uniform throughout the large bowel. However, in the small bowel in which synthesis is lower than in the large bowel, synthesis is significantly higher in the most proximal and distal segments than in the intermediate tissue. Anastomotic construction in either part of the bowel strongly increases collagen synthetic capacity at the immediate wound site. The synthetic response is not restricted to the anastomotic site but appears to be more generalized and is, in the small bowel, to some extent specific for collagen since the collagen synthetic capacity is increased far more than the capacity to produce noncollagenous protein. Anastomotic construction in the colon has only minor, although sometimes significant, effects on collagen synthetic capacity in the ileum, and vice versa. PMID- 1415944 TI - Samuel Preston Moore: Surgeon-General of the Confederacy. AB - Samuel Preston Moore was trained as a military surgeon in the US Army but resigned his commission and was appointed Surgeon-General of the Confederate States Army Medical Department at the beginning of the American Civil War. He reformed the mediocre medical corps by raising recruiting standards and improving treatment protocols and by placing the most capable surgeons in positions of authority. He improved the ambulance corps and directed the construction of many new hospitals for Confederate casualties. He was directly responsible for the barracks hospital design, which is still used today. He established the Confederate States Medical and Surgical Journal and directed a successful effort to develop substitutes for scarce pharmaceuticals from the indigenous flora of the South. He founded the Association of Army and Navy Surgeons of the Confederate States of America. With skill and dedication, Dr. Moore transformed the medical corps into one of the most effective departments of the Confederate military and was responsible for saving thousands of lives on the battlefield. PMID- 1415945 TI - Abdominoinguinal incision in resection of pelvic tumors with lateral fixation. AB - Large tumors in the area of the iliac fossa, external iliac vessels, wall of the lesser pelvis, and pubic bone are often considered unresectable through conventional abdominal incisions due to the lack of exposure, or they are managed with hindquarter amputation. The abdominoinguinal incision provides the necessary exposure for en-bloc resection of many of these tumors. It involves a lower midline incision that is extended transversely to the mid-inguinal point on the side of involvement and then vertically, over the course of the femoral vessels, which are exposed. The rectus abdominis is divided off the pubic crest and the inguinal ligament off the pubic tubercle, and the inferior epigastric vessels are ligated and divided at their origin. This allows in-continuity exposure of the lower abdomen, pelvis, and the groin in one field and dramatically improves the exposure. PMID- 1415946 TI - Utility of an oral examination in a surgical clerkship. AB - To evaluate the utility of the oral examination in a surgical clerkship, we designed a prospective and randomized study to relate the subjective impressions of experienced examiners with an objective measure of cognitive knowledge. The examiners were asked to score the student's performance as honors, high satisfactory, satisfactory, or unsatisfactory, according to their subjective impression of the student's ability. Student performance was grouped according to oral examination performance. The cognitive performance in the honors group was significantly better than that of the other groups (Student's t-test, p = 0.05). There was a significant difference in cognitive performance for oral examination groups throughout the rotations (analysis of variance, p = 0.000; Kruskal Wallis, p = 0.05). The oral examination is useful to identify a high level of cognitive achievement but cannot discriminate between groups of median to low competence. It should be used for educational feedback, career counseling, residency recommendations, and professional development. PMID- 1415947 TI - Composite resident work week. AB - During a 4-week period, all residents in the Wright State University School of Medicine Department of Surgery residency program were required to keep a log of their daily activities. Times were collected for the following resident activities: patient rounds, work-ups, laboratory data review, consults, meetings with attending physicians or patient families, phone calls, teaching conferences, medical student teaching, library time, clinics, attendance at codes, emergency department visits, on-call time, medical records committee meetings, and time scrubbed. The composite average weekly hours by resident year were 83.4 hours [postgraduate year (PGY)-1], 78.4 hours (PGY-2), 60.2 hours (PGY-3), 79.6 hours (PGY-4), and 80.9 hours (PGY-5). More than 50% of the resident work week cards were for less than 80 hours. Three activities (patient rounds, time scrubbed, and on-call) accounted for the majority of the residents' hours, but the average week, deleting educational and administrative hours, was less than 80 hours for all residents. PMID- 1415948 TI - Complications and diagnosis of Meckel's diverticulum in 776 patients. PMID- 1415949 TI - Intestinal obstruction complicating pregnancy. AB - Intestinal obstruction is a rare but serious complication of pregnancy with significant maternal and fetal mortality. The reported incidence of intestinal obstruction complicating pregnancy varies widely, from 1 in 66,431 to 1 in 1,500 deliveries. A retrospective review of 66 cases of intestinal obstruction complicating pregnancy and the puerperium, including 2 cases from our institution, revealed that the most common causes of mechanical obstruction were adhesions (58%), volvulus (24%), and intussusception (5%). Seventy-seven percent of the patients with obstruction due to adhesions had undergone previous abdominal or pelvic surgery. Presenting symptoms and signs were similar to those of the nonpregnant patient; abdominal pain was present in 98% of patients, vomiting in 82%, and tenderness to palpation in 71%. In 82% of patients, obstruction was evident on radiographic evaluation. Prompt management of obstruction is essential; the median length of time from admission to laparotomy in the 66 patients was 48 hours. Bowel strangulation requiring resection was present in 23% of patients. Thirty-eight percent of patients completed term pregnancies after operative resolution of obstruction; total maternal mortality was 6%, and total fetal mortality 26%. Thus, both mother and fetus are at risk when intestinal obstruction complicates pregnancy. Clinical suspicion of the presence of obstruction and aggressive intervention are required to decrease the morbidity and mortality of this rare complication of pregnancy. PMID- 1415950 TI - Molecular mechanisms of tumor formation. AB - DNA is the fundamental guide for the cell's processes. The alterations in DNA that can lead to abnormal or absent proteins and the role of chromosomal alterations in changing the function of the DNA are reviewed. The role of viruses in derailing a cell's normal functions, the major mechanisms of oncogene action, and tumor suppressor genes are also discussed. PMID- 1415951 TI - Indications for operative cholangiography. PMID- 1415952 TI - The future of general surgeons. PMID- 1415953 TI - Heparin in the treatment of deep venous thrombosis. PMID- 1415954 TI - General surgery training. PMID- 1415955 TI - Dysplasia. Rest in peace? PMID- 1415956 TI - The distribution of Merkel cells in human fetal and adult skin. AB - Merkel cells (MCs) have been a subject of investigation in human and animal studies for over a century, but their origin, function(s), and exact distribution in human skin remain largely unknown. The objectives of the present study were to quantify these cutaneous neuroendocrine cells in fetal and adult human skin, using an immunohistochemical marker (neuron-specific enolase) and morphometric methods. Our results indicate that, in postnatal life, MC are sparsely distributed along the undersurface of epidermal and occasionally adnexal epithelium in an approximate range of 0.1-1.0 MCs per centimeter of basal zone. They are most numerous on volar skin and least on genital skin, and on the face they have a primarily perifollicular orientation. Fetal samples have shown that MCs appear between the 15th and 18th week of gestation and are most abundant on volar skin. They appear to arise within the epidermis, and are initially numerous and later diminish with increasing gestational age. Their predominance in intrauterine life suggests a functional role in growth and development. PMID- 1415957 TI - Dermatofibroma with osteoclast-like giant cells. AB - Dermatofibroma (DF), or cutaneous fibrous histiocytoma, is a common cutaneous tumor with many variants that may arise from alterations in the morphology and composition of its various components. One type that has not received much attention is DF with osteoclast-like giant cells. Two cases of this rare tumor are described. The importance of this tumor lies in the possible histologic confusion with a variety of benign and malignant neoplasms, including giant cell tumor of tendon sheath, giant cell tumor of bone, and giant cell reparative granuloma. PMID- 1415958 TI - Evolution of B-cell lymphoma from pseudolymphoma. A multidisciplinary approach using histology, immunohistochemistry, and Southern blot analysis. AB - Cutaneous B-cell lymphomas are rare neoplasms that can present as lesions involving solely the skin or develop in association with a systemic lymphoma. Histologically they are often difficult to differentiate from pseudolymphomas, and the use of immunohistochemistry may be necessary to correctly classify them. We report a study of multiple skin lesions in a patient who initially presented with multiple pseudolymphomas, apparently associated with an immune response to the dye of his tattoos. Over a period of 4 years his skin lesions evolved from histologically benign and immunologically polyclonal pseudolymphomas to a histologically malignant and immunologically monoclonal B-cell large cell lymphoma. Genotypic analysis with a probe for the heavy-chain immunoglobulin gene demonstrated the presence of clonal B-cell populations in all of the pseudolymphoma biopsy samples as well as in the subsequent lymphoma tissue samples, with a pattern of clonal bands suggestive of evolution of the B-cell clones. These findings suggest that the development of B-cell lymphoma in this patient was related to a persistent abnormal immune response to the chronic antigenic stimulus of the dye of the tattoo. The presence of clonal B-cell populations in pseudolymphoma by Southern blot analysis may be useful in predicting those patients who will subsequently develop overt lymphoma. PMID- 1415959 TI - Intravascular spread of keratoacanthoma. An alarming but benign phenomenon. AB - We report a patient with a keratoacanthoma of the scalp in which there was invasion of several medium-sized vessels by the tumour at a distance from the main lesion. A marked inflammatory response within the invaded vessels as well as a benign clinical course do not suggest that this phenomenon represents malignant transformation. PMID- 1415960 TI - Multicentric reticulohistiocytosis. Immunohistological and ultrastructural study: a pathology of dendritic cell lineage. AB - A case of multicentric reticulohistiocytosis is presented with extensive immunohistochemical study of the infiltrate in both paraffin and cryostat sections. Factor XIIIa dermal dendrocyte marker was demonstrated in the cytoplasm of histiocytes, which has not been reported previously in this disease. In addition, the S100 protein stained positive. This immunophenotyping study suggests a dermal dendrocyte lineage with an unusual expression of S100 protein. PMID- 1415961 TI - Auricular granuloma annulare. A consequence of trauma? AB - Localized granuloma annulare (GA) is a cutaneous disorder characterized by the formation of palisading necrobiotic granulomas. Although trauma and vasculitis have been considered, the etiology of most cases remains obscure and the disease is generally considered to be idiopathic. The condition may occur at any age and at any site, but usually involves the hands or feet of children or young adults, predominantly affecting females. We present two cases occurring as nodules involving the external ears of males. One of these showed a bilateral distribution and was clearly related to trauma. PMID- 1415962 TI - A critical analysis of textbooks of dermatopathology in historical perspective. Part 3. PMID- 1415963 TI - Who was Sophie Spitz? The woman behind the eponym. PMID- 1415964 TI - Naming acquired melanocytic nevi. Common and dysplastic, normal and atypical, or Unna, Miescher, Spitz, and Clark? AB - Acquired melanocytic nevi are among the commonest neoplasms in man, yet classification of them has proven elusive and elucidation unsatisfactory. From "active junctional nevus" to "dysplastic nevus," the brains of clinicians and histopathologists have been boggled and the psyches and skin of patients have been served badly. This essay advocates eponymic designations for acquired melanocytic nevi, all of which are common, as the surest route to comprehensive classification of them. PMID- 1415965 TI - Dysplasia. An abused and confusing terminology. PMID- 1415966 TI - Do you use the term "dysplasia"? If so, what do you mean by it, and if not, why not? PMID- 1415967 TI - Nomenclature for flat lesions of melanoma: a response. PMID- 1415968 TI - Regurgitation and oesophageal rupture with cricoid pressure: a cadaver study. AB - The efficacy of cricoid pressure was studied in 10 adult cadavers. The oesophageal pressure that would result in regurgitation during measured values of cricoid pressure was determined. Oesophageal pressure, recorded by a 2 mm diameter oesophageal tube, was increased by oesophageal distension with saline, and incremental levels of cricoid force, 20, 30 and 40 Newtons, were applied with a cricoid yoke. With each 10 Newton increment of cricoid force there was a significant rise in the oesophageal pressure required to provoke regurgitation (p < 0.01). Thirty Newtons of cricoid force prevented regurgitation of saline in all cadavers with oesophageal pressures of up to 40 mmHg. Rupture of the oesophagus occurred in three cadavers: one at 30 and two at 40 Newtons of cricoid force, but there was no rupture at 20 Newtons of cricoid force. In the other seven cadavers oesophageal pressures were also studied with a 4.6 mm diameter (14 FG) oesophageal tube, which did not reduce the efficacy of cricoid pressure in preventing regurgitation. PMID- 1415969 TI - Thoracic electrical bioimpedance measurement of cardiac output and cardiovascular responses to the induction of anaesthesia and to laryngoscopy and intubation. AB - Noninvasive methods of determining cardiac output (by thoracic electrical bioimpedance) and arterial pressure (by intermittent oscillometry) were used to record minute-by-minute changes in heart rate, mean arterial pressure, stroke volume, cardiac output and systemic vascular resistance following induction of general anaesthesia and laryngoscopy and intubation in 60 healthy female patients who were either unpremedicated, or premedicated with temazepam or papaveretum hyoscine. Anaesthesia was induced with a sleep dose (3-5 mg.kg-1) of thiopentone and maintained with 70% nitrous oxide in oxygen with 0.5-1% enflurane. Tracheal intubation was facilitated by administration of vecuronium 0.1 mg.kg-1. Mean arterial pressure and cardiac output decreased maximally 5 min after induction in all premedication groups by mean estimates of 21-25% and 14-22% respectively. Heart rate increased initially one minute after induction, but decreased to less than the baseline value 5 min after induction. Systemic vascular resistance was unchanged. The stimulus of laryngoscopy and tracheal intubation was accompanied by a significant pressor response and tachycardia one minute after intubation (with mean increases in mean arterial pressure and heart rate of 29-34% and 22 33% respectively). The increase in mean arterial pressure was secondary to an increase in systemic vascular resistance (36-57%), and was accompanied by a decrease in stroke volume (-25 to -31%). These changes were significant in all three groups. Cardiac output decreased only in unpremedicated patients. There were wide variations in the different haemodynamic indices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1415970 TI - Implicit memory tested in children during inhalation anaesthesia. AB - Memory for stimuli presented during inhalation anaesthesia was tested in 80 children undergoing eye surgery. Two groups were exposed, in a random double blind study, to repeated neutral phrases including either the colour orange or green. A postoperative colouring task was used as a test of implicit memory to detect any preference for the colour named under anaesthesia. No colour preference attributable to implicit memory could be demonstrated. One patient had a distinct preference for the named colour. No patient remembered any intra operative events. PMID- 1415971 TI - Catecholamine response to laryngoscopy and intubation. The influence of three different drug combinations commonly used for induction of anaesthesia. AB - The haemodynamic response and changes in plasma catecholamine concentrations associated with laryngoscopy and tracheal intubation were compared during anaesthesia employing three strictly standardised techniques with commonly used drug combinations. Thirty-six patients were investigated consecutively resulting in 12 patients in each of three study groups. Anaesthesia was induced with thiopentone 5 mg.kg-1 (group 1), fentanyl 6 micrograms.kg-1 with thiopentone 5 mg.kg-1 (group 2), or midazolam 0.2 mg.kg-1 with fentanyl 6 micrograms.kg-1 (group 3). Undesirable changes in haemodynamic effects and an elevation of plasma catecholamine concentrations during laryngoscopy and intubation occurred in group 1. Heart rate and mean arterial pressure increased significantly (34% and 23% respectively). Noradrenaline concentration increased by a maximum of 147%. The addition of fentanyl (groups 2 and 3) attenuated the adverse haemodynamic response and elevation of plasma catecholamine concentrations; heart rate and mean arterial pressure did not differ from pre-intubation values and plasma catecholamine concentrations decreased steadily. Substitution of thiopentone by midazolam in combination with fentanyl abolished the adverse haemodynamic response and modified the increase in plasma catecholamine concentrations. 'High dose' opioid anaesthesia is not necessary to produce optimal conditions during laryngoscopy and intubation. PMID- 1415972 TI - Opioid sensitivity of chronic pain: a patient-controlled analgesia method. AB - Twenty-two patients with chronic pain of malignant or nonmalignant origin were given intravenous morphine by patient-controlled analgesia. A prestudy judgment was made from the characteristics of the pain as to whether it was nociceptive or neuropathic. Analgesic efficacy was assessed by a nurse-observer; adverse events were noted and plasma morphine and metabolitie concentrations measured. Three categories of opioid response were distinguished. Good responders obtained > 70 mm relief on the visual analogue scale, with minimal or manageable adverse events. Moderate responders obtained < 70 but > 30 mm relief with more problematic adverse events, and poor responders had < 30 mm relief with troublesome adverse events. This method for the study of opioid sensitivity allowed a wide dosage range to be studied. The simultaneous analgesic and adverse event measurements showed that the spectrum of observed response was wide, and response category could be judged for the majority by 4 h. In those with poor or moderate response, adverse event severity limited further dose increment. The relationship between pain characteristics and response showed that some pains judged to be neuropathic had a good response to opioid (5/13), and some pains judged to be nociceptive did not (5/14). The study suggests that the pattern of response is not as black and white as the prediction of good response from nociceptive pain and poor from neuropathic pain would suggest, although nociceptive pain was more likely than neuropathic pain to show a good response. For the moderate responders opioid titration may, in the absence of other effective treatments, be useful, but the analgesic endpoint may not be totally satisfactory. The method provides an operational definition of opioid sensitivity. PMID- 1415973 TI - Isoflurane and propofol for long-term sedation in the intensive care unit. A crossover study. AB - Propofol and isoflurane have been reported recently to offer better sedation than alternative agents in patients who require long-term ventilation in the Intensive Care Unit. This is the first report of a direct comparison between propofol and isoflurane. Twenty-four patients predicted to require artificial ventilation for at least 48 h were entered into a randomised crossover study to monitor sedation quality and time to recovery from sedation. There were no significant differences between the two agents in either end-point, with over 95% optimal sedation achieved by the use of each drug. Few adverse events were noted. Technological advances in the administration of volatile agents as long-term sedatives in the Intensive Care Unit may facilitate their more widespread use. PMID- 1415974 TI - The Riyadh Intensive Care Program applied to a mortality analysis of a teaching hospital intensive care unit. AB - A computerised system of prediction of death using the Riyadh Intensive Care Program was applied retrospectively over a 17-month period to data collected prospectively on 1155 patients admitted to our intensive care unit. Variables which enable organ failure scores to be generated were recorded daily to make these predictions. Consultant medical opinion predicted that outcome was hopeless in 55% (115/209) of the patients who died. The predictive power of the computer demonstrated a sensitivity of 14.8% and a specificity of 99.8%. It is possible that the occurrence of three false predictions of death in the latter part of the series may have been related to a change in our antibiotic policy. We would be unhappy to recommend the general use of a computerised program for prediction of death without careful explanation of its significance and dangers. PMID- 1415975 TI - Acute isoniazid poisoning. AB - We present two cases of acute isoniazid poisoning in patients who ingested 7.5 g and 5.0 g of isoniazid respectively, with the intention of committing suicide. Both were admitted unconscious, with ventilatory insufficiency and convulsions. Hepatic dysfunction and peripheral neuropathy were notable complications. PMID- 1415977 TI - Managing the airway in cervical spine injury. A review of the Advanced Trauma Life Support protocol. AB - The American College of Surgeons' Advanced Trauma Life Support protocol for managing the airway in patients with a cervical spine injury is reviewed. The relative risks and benefits of oral and nasotracheal intubation are discussed and the potential hazards of alternative methods of airway control are considered with particular respect to British practice. PMID- 1415976 TI - Does hypothermia protect against the development of hepatitis in paracetamol overdose? AB - A 24-year-old female presented in hospital following self-poisoning with a dose of greater than 30 g of paracetamol (acetaminophen), taken both as co-proxamol (dextropropoxyphene and paracetamol) and paracetamol. She arrived in hospital more than 18 h after ingestion of the drug. On admission, she was profoundly hypothermic, with a rectal temperature of 19 degrees C. Her paracetamol level was 943 mumol.l-1 which, when related to the time of ingestion, implied a very high risk of hepatocellular damage as well as fulminant liver failure, even if she was treated with the antioxidant n-acetylcysteine. The patient's condition was stabilised by initial resuscitation with fluids, vasoactive drugs, and active rewarming. N-acetylcysteine therapy was begun promptly. This patient's liver function tests remained entirely normal in spite of the delay in presentation and she made a rapid and complete recovery. This remarkable clinical course indicates a possible role for therapeutically induced hypothermia in the management of severe paracetamol overdose, particularly in the group of patients who seek medical attention some hours after ingestion of the drug and who therefore remain at high risk, despite treatment with n-acetylcysteine. PMID- 1415978 TI - The pre-operative anaesthetic visit. Its value to the patient and the anaesthetist. AB - One hundred and thirty-two patients staying in hospital more than 24 h were visited pre- and postoperatively. Patients were asked a standard set of questions, and 39% could not remember accurately what they were asked. This has important medicolegal implications. In 15% of patients, information that significantly altered subsequent anaesthetic management was discovered, but in less than 3% would ignorance of the patient's condition have required postponement of the surgery. We conclude that the major reason for a pre operative visit by an anaesthetist is that patients appreciate it, rather than it being medically necessary. PMID- 1415980 TI - Oxygen dynamics: more science at the bedside. PMID- 1415979 TI - Chronic pain management training for senior registrars in anaesthesia. AB - In 1985 and 1990 postal questionnaires were sent to anaesthetic senior registrars in training in the United Kingdom to determine the extent of higher specialist training in chronic pain management. There were wide variations in training and experience amongst senior registrars. Overall there was little change between 1985 and 1990. In particular the number of anaesthetic senior registrars who felt equipped to undertake a consultant post with an interest in chronic pain management had not increased. PMID- 1415981 TI - Problems of thermodilution cardiac output measurements in small patients. PMID- 1415982 TI - Pneumothorax and insertion of interpleural catheters. PMID- 1415983 TI - Neurological sequelae in children after prolonged propofol infusion. PMID- 1415984 TI - Propofol sedation of children. PMID- 1415985 TI - Fibreoptic intubation under general anaesthesia need not be associated with hypoxia and hypotension. PMID- 1415986 TI - Combined epidural/spinal anaesthesia for caesarean section--single-space double barrel technique. PMID- 1415987 TI - Delayed vascular puncture following axillary brachial plexus sheath cannulation. PMID- 1415988 TI - A knotty problem with two central venous catheters. PMID- 1415989 TI - Nitrous oxide and laryngeal mask cuff pressure. PMID- 1415990 TI - Guided intubation via the laryngeal mask. PMID- 1415991 TI - Removal of laryngeal mask airway during light anaesthesia. PMID- 1415992 TI - Gas embolism during attempted laparoscopic vagotomy. PMID- 1415993 TI - Leaking Datex sampling set for the end-tidal CO2 monitor. PMID- 1415994 TI - Allegation of sexual assault following midazolam sedation in a man. PMID- 1415995 TI - False-positive aspiration tests in CVP line placement. PMID- 1415996 TI - A further persistent leak. PMID- 1415997 TI - Atracurium block prolonged by low dose tubocurarine. PMID- 1415998 TI - Intrathecal pethidine in a patient with heart block. PMID- 1415999 TI - Misuse of helium. PMID- 1416000 TI - 'Duck speech'. PMID- 1416001 TI - Transdermal hyoscine. PMID- 1416003 TI - Nasal intubation and pharyngoplasty--a word of warning. PMID- 1416002 TI - A simple solution. PMID- 1416004 TI - Publications on anaesthesia in 1847. PMID- 1416005 TI - [Perioperative diagnosis of acute myocardial ischemia]. AB - The prevalence of coronary artery disease substantially affects both cardiac and noncardiac surgery. Assuming that biometric data reported from North America are representative for Germany, the following incidences can be estimated: around 1 million out of 8 million patients operated upon each year will suffer from coronary artery disease, and 15,000 of these patients will have a perioperative myocardial infarction. Since a close relationship has been shown between pre-, intra-, and postoperative myocardial ischaemia and postoperative cardiac morbidity and mortality, early diagnosis and therapy of acute perioperative myocardial ischaemia is warranted. The purpose of this review is to weigh critically the various methods for diagnosis of myocardial ischaemia in view of their practicability and cost/benefit relationship in the perioperative setting. The symptoms of angina pectoris are unreliable in the perioperative period, since patients are premedicated preoperatively, without symptoms during anaesthesia, and usually receive analgesics postoperatively. Intraoperative detection of myocardial ischaemia focuses on standard electrocardiography (ECG) with on-line registration of the ST-segment in two leads (usually leads II and V5) and automatic analysis of ST-segment deviation, achieving a sensitivity of 80% in the detection of myocardial ischaemia. Measurement of regional wall motion abnormalities with trans-esophageal echocardiography (TEE) is a more sensitive method of myocardial ischaemia detection compared to ECG. However, several reasons preclude the broader application of this method in the perioperative phase: (1) it lacks validation by an accepted and independent gold standard; (2) there is a wide spectrum of false-positive findings (considerable interindividual variations in left ventricular contraction, bundle branch blocks, hypertension, hypervolemia); (3) changes in the inferior and apical segments of the left ventricle cannot be detected by single-plane TOE. Detection in these segments might be achieved with biplane echocardiography, but few data on this improved technique are presently available; (4) the method is semi-invasive and might be not applicable during periods with a high incidence of myocardial ischaemia, e.g., intubation, the end of anaesthesia, and extubation; (5) anaesthetists seldom fulfil standard guidelines in echocardiography training; and (6) the method is expensive, which also limits its broader application. Cardiokymography, a noninvasive technique, allows analog representation of anterior wall motion.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1416006 TI - [Ventilatory changes during laparoscopic cholecystectomy]. AB - During the past 2 years in Europe and the USA laparoscopic cholecystectomy (LC) has become a widely practiced procedure. Nevertheless, the effects of long lasting laparoscopic procedures on carbon dioxide elimination have not yet been systematically investigated. METHODS. Approval from the institutional research review board was obtained, as was written informed consent from the patients. Eleven patients undergoing LC were studied. Patient age ranged from 31 to 67 years. All patients received total intravenous anaesthesia (fentanyl, propofol, vecuronium, DHB). Controlled ventilation with a tidal volume of 12-14 ml/kg was administered. Before introduction of anaesthesia a cannula was inserted into the left radial artery. Blood gas analysis was undertaken just before introduction, just before insufflation of carbon dioxide, and thereafter at two intervals, after reaching an intra-abdominal pressure of 12 mm Hg, 15 min apart. Oxygen consumption and carbon dioxide output were measured using a calorimeter (Deltatrac TM, Datex). Intra-abdominal pressure was maintained at 12 mm Hg during the operation. RESULTS. After onset of the pneumoperitoneum inspiratory peak and plateau pressure showed an increase by more than 40%. During the operation respiratory minute volume had to be increased by about 30-40% to maintain normocapnia. Oxygen consumption remained nearly unchanged during the procedure while carbon dioxide output increased up to 38% 60 min after onset of the pneumoperitoneum. D(a-A) CO2 showed no significant change, indicating no increase in dead space. Beginning with the insufflation there was a significant increase in mean arterial pressure that lasted until the end of the procedure. CONCLUSION. The described effects of carbon dioxide insufflation, especially the extent of carbon dioxide resorption, define the need for careful monitoring of respiratory function during LC, especially in patients with preexisting cardiopulmonary disease. PMID- 1416007 TI - [Pharmacodynamic effects of S-(+)-ketamine on EEG, evoked potentials and respiration. A study in the awake dog]. AB - Until recently, only the racemic mixture of ketamine has been used in anaesthesia. Little is known of the central nervous effects of the pharmacologically more potent S(+)-isomer. Information in regard to the putative receptor site involved in the mediation of its anaesthetic/analgesic effect is particularly sparse. METHODS. In order to evaluate the anaesthetic and antinociceptive properties of S(+)-ketamine, a dose-response relationship of the compound on the EEG, somatosensory-evoked potentials (SEP), and respiration was established. Increasing doses (2, 5, 10, 20 mg/kg) were given to trained and awake dogs (n = 10) at 10-min intervals. In order to detect a possible opioid receptor-related interaction, an antagonist of the methoxymorphinane series (cyprodime 80 g/kg i.v.) with higher selectivity than naloxone for the mu receptor was given at the end. RESULTS. Compared to controls, S(+)-ketamine induced a dose-related increase in output in the theta-(3-8 Hz) band and an increase in output in the alpha-domain (8-13 Hz) following 20 mg/kg. Both effects were reversed completely by the opioid antagonist. At low doses (2-5 mg/kg) there was an increase in output (P less than 0.05) in the beta-(13-30 Hz) and a concomitant decrease in output (P less than 0.05) in the delta-(0.5-3 Hz) band. These effects were reversed with increasing doses (5-10 mg/kg). After 20 mg/kg, however, output in the delta-domain increased while power in the beta band decreased significantly (P less than 0.005) when compared to controls. Both effects were reversed by the opioid antagonist. Compared to controls, the reversal resulted in a 12% increase in output in the beta- and a 49% decrease in output in the delta-domain. In SEP, S(+)-ketamine induced a dose-related increase in peak latency and depression of amplitude of more than 50% when compared to controls. While latency changes were completely reversed, amplitude height was only partly restored by the antagonist. Respiration was depressed in a dose related fashion (PaO2 decreased, PaCO2 increased). Hypoxaemia was fully reversed by the antagonist; hypercapnia was only partly reversed. CONCLUSION. The results support the presumption that the S(+)-isomer of ketamine induces opioid mu receptor-mediated central effects. Hypersynchronisation of the EEG suggests a deep plane of anaesthesia after S(+)-ketamine. The pronounced blockade of impulses in the sensory nervous pathways suggests an efficient analgesic effect that is partly mediated by the opioid-receptor. The respiratory depression may be of importance when S(+)-ketamine is used in high dosages in man. PMID- 1416008 TI - [Humidification and heating of anesthetic gases during pediatric anesthesia using the Cicero Anesthesia Workstation]. AB - A series of 52 infants underwent general or urological surgery; all were ventilated with the CICERO. Two different flows of fresh gas were used. In group I (n = 21) the fresh gas flow was set exactly at the level of the minute volume, representing a half-open, non-rebreathing system. In group II (n = 31) the fresh gas flow was adjusted to 10% of the required minute volume. Temperature and relative humidity of the inspired gas were measured continuously close to the tracheal tube. Anaesthesia was accomplished with 2 vol% isoflurane, 21-30 vol% oxygen in nitrous oxide. The results were compared with those achieved with our time-tested paediatric equipment, a SERVO 900D ventilator with a Fisher-Paykel humidifier (Group III, n = 35). Using a high fresh gas flow, no increase in relative humidity in the inspired gas could be detected. The values varied between 12% and 25% (group I). Reducing the flow of fresh gas as indicated above resulted in an increase in the relative humidity (group II). Over the evaluated period of 2 h, humidity increased slowly from an initial mean value of 20% to a maximum of something over 70%. Using the SERVO 900D ventilator combined with the Fisher-Paykel humidifier, humidity reached a value of greater 90% within 10 min after activation of the heated cascade. Humidity in the inspired gas should exceed 70% to avoid damage to infant airways. This will not be attained until after more than 2 h with unaided breathing systems, by when most operations performed on paediatric patients will already be over. Condensed water may aspirated by small infants. This potentially dangerous situation was only encountered in the CICERO circuit, and not in the system protected by the Fisher Paykel cascade. Dry gases can result in thickened mucous and in obstruction of a small tracheal tube, which requires emergency reintubation. With artificial airways dry gases damage the ciliated epithelia of the trachea and cause loss of water and body heat. The temperature of the "cold" gases varied within a range of 21-33 degrees C and could not be adjusted by the anaesthetist. In the CICERO system, heating the gases at the valve only prevents mechanical failure caused by water condensation. In pediatric anaesthesia, variable heating and non-condensing humidity are essential. The dry and heated gases of the CICERO are not acceptable in the daily practice of paediatric anaesthesia. PMID- 1416009 TI - [Postspinal headache. A comparison of the 24G Sprotte syringe and a 29G Quincke needle]. AB - PATIENTS AND METHODS: A randomised study was performed to compare the frequency of postdural puncture headache in 56 patients who underwent spinal anaesthesia for extra-corporeal shockwave lithotripsy using either a Sprotte 24 G (n = 28) or Vygon 29 G or Quincke type needle (n = 28). Frequency of headache was recorded in a similar group of 28 patients who received general anaesthesia. RESULTS: Dural puncture was easier with the Sprotte 24 G cannula than with the less stable Quincke needle, as documented by a significantly shortened time for insertion of the cannula (4.6 +/- 2.6 vs 8.6 +/- 6.3 min, P less than 0.005). The total frequency of post-operative headache was 57% in the Vygon 29 G group and 25% in the Sprotte 24 G group; 21% of patients in the general anaesthesia group complained of headache. Frequency of postdural puncture headache, classified as being posture-related, was 25% in the 29 G Vygon group, compared with 11% in the 24 G Sprotte group (P = 0.148). When only moderate and severe postdural puncture headache was considered, there was a significant difference (25% vs. 4%; P = 0.026) in favour of the Sprotte cannula. DISCUSSION AND CONCLUSIONS: Thus, the 24 G Sprotte needle was at least as effective as the 29 G Vygon needle, and there is a suggestion that the former is more effective in minimising the incidence of moderate or severe postdural puncture headache. PMID- 1416010 TI - [Spinal endoscopy in the detection of problems caused by continuous spinal anesthesia]. AB - Continuous spinal anaesthesia has a number of advantages, but there are a number of drawbacks as well: difficulties in threading the catheter, distribution of the local anaesthetics and the development of cauda equina syndrome. Spinaloscopy was done to visualize the fate of catheters during and after their insertion, as well as the distribution of local anaesthetics injected through these fine-bore catheters. METHOD. The studies were conducted in preserved and fresh cadavers donated to the Anatomic Institute for Medical Studies. The spinal column from T12 to S1, together with the back musculature (in order to preserve the normal curvature of the spine) were removed from the cadaver. Spinaloscopy was done with a 4 mm endoscope with a 0 degree optic (Storz, Tutlingen, FRG). All observations were made from the lumbosacral region of the dissected preparation. In this fashion, it was possible to observe the insertion of the spinal needle used to introduce the catheter into the subdural space. The distribution of local anaesthetics injected through a 22-gauge spinal needle or a 28-gauge catheter was shown by injecting 0.5% hyperbaric bupivacaine colored with a small amount of 1% methylene blue. Pictures were taken 15, 30 and 45 s after beginning the injection. RESULTS. Difficulty in threading the catheter: our observations indicate that the difficulty in inserting microbore catheters is most likely due to inserting the needle too far. It is impossible for the catheter to bend and be inserted into the subarachnoid space. In many cases the catheter encountered the anterior wall of the spinal canal and would slide along various structures. Distribution of the drug: the injection is better dispersed with a 22-gauge needle and it completely fills the subarachnoid space. The local anaesthetics injected through the 28-gauge nylon catheter (Kendall Healthcare, Mansfield, Mass.) are distributed in the dependent portions of the spinal canal. If high doses and a high concentration are injected, the distribution pattern may result in an overconcentration in some parts of the subarachnoid space. Possibility of trauma: the catheter stretches around the roots, the potential for trauma is that untoward stress may be applied to the root, either during full insertion of the catheter or during its withdrawal. CONCLUSION. Spinaloscopy was done in a non fixated anatomic spinal column preparation with a 4 mm 0 degree endoscope (Storz, Tuttlingen, FRG). Based on our observations, we conclude: The catheter should only be inserted 2 cm into the subarachnoid space. This may decrease the risk of malpositioning. After the tip of the catheter has reached the subarachnoid space, the stylet should be with drawn 2 or 3 cm to minimize the risk of nerve injury and/or bleeding. PMID- 1416011 TI - [The effect of adding clonidine to mepivacaine. Axillary brachial plexus blockade]. AB - Clonidine (Cl) added to local anaesthetics (LA) prolongs the duration of both anaesthesia and analgesia after peripheral nerve blocks. In this study, we investigated the dose-dependent effect of Cl added to mepivacaine (M) on clinical efficacy, onset, and regression time of brachial plexus block. METHODS. Ninety patients were randomly assigned to one of three groups. Every patient received 46 ml of a mixture containing 400 mg M (pH adjusted with NaHCO3 to 7.25) and either 0.9% NaCl (group A), 0.12 mg Cl (group B), or 0.24 mg Cl (group C). The axillary block was performed using the catheter technique. In a double-blind fashion, the onset of sensory and motor blockade was tested every 5 min for 30 min. Duration of anaesthesia, analgesia, and motor blockade (time between injection and return of sensation, onset of pain, or ability to move, respectively) was assessed using a questionnaire. M plasma levels were measured by HPLC in 10 patients from each group for up to 120 min. Blood pressure (BP), heart rate (HR), and respiratory rate (RR) were measured for up to 120 min. Sedation was assessed using a verbal rating scale. RESULTS. There was no difference in the onset of blockade. There was dose-dependent prolongation of the duration of anaesthesia, analgesia, and motor blockade with significant differences between groups C and A regarding all three parameters, between groups C and B regarding duration of anaesthesia, and between groups B and A regarding duration of analgesia. There was no significant difference in M plasma levels. Although there was only a slight but significant decrease in mean BP values in groups B+C and no difference in HR and RR, 2 patients (1 group B, 1 group C) had marked decreases in BP and HR (less than 70 mmHg systolic resp. less than 50/min) after 120 and 210 min. Sedation occurred in most patients receiving Cl. CONCLUSIONS. Addition of Cl to LA produces a dose dependent prolongation of anaesthesia, analgesia, and motor blockade. Neither the onset time nor the number of patients with adequate surgical anaesthesia was influenced by Cl. Considering the M plasma levels, it is unlikely that the prolongation of the block is caused by local vasoconstriction, which is proposed to be the mechanism of action of epinephrine. The mean differences in haemodynamic parameters were not of clinical relevance, but the two dramatic drops in BP and HR, probably caused by Cl, were significant. PMID- 1416012 TI - [Surfactant administration in acute respiratory failure]. AB - We report the case of a 21-year-old man who developed adult respiratory distress syndrome (ARDS) after severe lung contusion due to a car accident. At the scene of the accident the patient was awake and oriented, but there were signs of hypoxaemia (SaO2 by pulse oximetry: 86%). The trachea was intubated in the emergency room and, after diagnosis of multiple rib fractures on the right side (the patient nos. 4-11) and emergency treatment, was extubated 16 h later. During spontaneous breathing there was no improvement of pulmonary function, and the patient was transferred to the intensive care unit 5 days later and reintubated because of acute respiratory failure. He then developed the signs of severe ARDS. No improvement occurred during conventional ventilatory treatment including inversed-ratio ventilation, high-frequency ventilation, and ventilation via a double-lumen tube. On day 15 a bovine surfactant preparation (38 mg/kg body wt.) was instilled into both lungs. Initially there was deterioration of the pulmonary function, probably due to crusts in the bronchial mucous membrane. After aspiration of the crusts at bronchoscopy, there was progressive respiratory improvement. The inspired oxygen concentration and PEEP level could be reduced, and the ventilatory ratio normalised within 14 days. This therapeutic intervention improved pulmonary function and probably led to the successful outcome after 36 days of ventilatory support. PMID- 1416013 TI - [Comments on the paper by M. Fischer et al. Total intravenous anesthesia using propofol and alfentanil]. PMID- 1416014 TI - [Final comments on the letter by J. Van Aken on our paper. Nonsurgical removal of a knotted Swan Ganz catheter]. PMID- 1416015 TI - [Verification of the endotracheal tube placement]. AB - Verification of the correct position of the endotracheal tube is a daily routine task of every anaesthesiologist. Accidental intubation of the oesophagus is a very rare complication in absolute terms but still the most frequent preventable anaesthetic mishap with fatal outcome. Even the most experienced anaesthetist is not immune to this complication. Only vigilance on the part of the anaesthetist protects the patient. There is no absolutely reliable gold standard to diagnose the correct position of the tracheal tube. Visualization of the endotracheal tube between the vocal cords and a typical CO2 excretion waveform are two of the best practical signs. After every change of position of the patient, especially after flexion or extension of the head, the position of the tube must be checked again. The old aphorism is still valid: When in doubt, take it out. PMID- 1416016 TI - [Pain therapy with Toratex. Official satellite symposium of the Xth World Congress of Anesthesiology. The Haague, 15 June 1992]. PMID- 1416017 TI - The consequences of the isotope effect on proline dehydrogenation rates estimated by the tritium loss method. AB - Loss of tritium from a substrate is often used to estimate the rate of dehydrogenation. However, loss of 3H may be much slower than loss of H because of the tritium isotope effect. In order to assess the impact of the tritium isotope effect, loss of 3H from the C-5 position of proline during dehydrogenation by rat liver mitochondria and bacteroids from soybean (Glycine max [L.] Merrill) nodules was compared with appearance of 14C in products of [14C]proline dehydrogenation. Incubations were carried out in the presence of o-aminobenzaldehyde (added to trap the initial product, delta 1-pyroline-5-carboxylate). The fraction of total 14C products trapped by o-aminobenzaldehyde varied from 0.07 to 0.75 depending upon experimental conditions. With rat liver mitochondria, dehydrogenation of [14C]proline was between 3.27 and 9.25 times faster than dehydrogenation of 3H proline, depending upon assay conditions. Soybean nodule bacteriods dehydrogenated [14C]proline about 5 times faster than [3H]proline. We conclude the following: (i) the rate of proline dehydrogenation may be greatly underestimated by the tritium assay because of the tritium isotope effect, and (ii) the 14C assay may underestimate the rate of proline dehydrogenation if it is assumed that o-aminobenzaldehyde quantitatively traps delta 1-pyrroline-5 carboxylate under all conditions. The simplicity of the tritium assay makes it attractive for routine use. However, its use requires determination of the tritium isotope effect, under the specific conditions of the assay, in order to correct the results. The considerations discussed here have broad applicability to any dehydrogenase assay employing tritium loss. PMID- 1416018 TI - Lectin affinity electrophoresis for the separation of fluorescently labeled sugar derivatives. AB - Lectin affinity electrophoresis was applied to the separation of charged, fluorescent conjugates of disaccharides. Four fluorescent conjugates were prepared by reductive amination of alpha-D-Man-(1----3)-D-Man, alpha-D-Gal-(1--- 4)-D-Glc, alpha-D-Gal-(1----6)-D-Glc, and beta-D-Gal-(1----4)-D-Glc in the presence of 7-amino-1,3-naphthalenedisulfonic acid. These charged fluorescent disaccharide conjugates all have identical molecular weight and in the absence of conconavalin A lectin failed to separate either by agarose or by polyacrylamide gel electrophoresis. In the presence of either free or immobilized concanavalin A, agarose gel electrophoresis and polyacrylamide gel electrophoresis could separate the fluorescent conjugate of alpha-D-Man-(1----3)-D-Man from that of alpha-D-Gal-(1----4)-D-Gal, alpha-D-Gal-(1----6)-D-Glc, and beta-D-Gal-(1----4)-D Glc. PMID- 1416020 TI - Alkyl- and aryl-substituted salicyl phosphates as detection reagents in enzyme amplified fluorescence DNA hybridization assays on solid support. AB - Nine salicyl phosphate esters with hydrophobic substituents (5-phenyl, 5-(2,4 difluorophenyl), 5-tert-octyl, 5-cumyl, 5-(4-tert-butylphenyl, 5-(1-adamantyl), 5 (n-dodecyl), 5-(1,1-diphenylethyl, and 5-trityl) were synthesized and found to be good substrates for calf intestinal alkaline phosphatase. The enzymatic hydrolysis produced the corresponding salicylates, which were strongly fluorescent when excited by ultraviolet light around 300 nm with maximum emission at 420-435 nm. The salicylates were less soluble and/or more adhesive than the nonfluorescent salicyl phosphate substrates, resulting in localization of fluorescence signal, which is a requirement for membrane-based assays. The salicyl phosphates bearing 8-14 carbon substitutents were found to be suitable detection reagents for dot-blot DNA hybridization assays on nylon membrane using a biotinylated probe, allowing the detection of 125 pg of target pBR322 plasmid DNA using a simple apparatus consisting of a transilluminator, a camera. and a 455-nm cutoff optical filter. PMID- 1416019 TI - Biosynthesis of lipid-linked oligosaccharides. I. Preparation of lipid-linked oligosaccharide substrates. AB - In order to purify the glycosyltransferases involved in the assembly of lipid linked oligosaccharides and to be able to study the acceptor substrate specificity of these enzymes, methods were developed to prepare and purify a variety of lipid-linked oligosaccharides, differing in the structure of the oligosaccharide moiety. Thus, Man9 (GlcNAc)2-pyrophosphoryl-dolichol was prepared by isolation and enzymatic synthesis using porcine pancreatic microsomes, while Glc3Man9(GlcNAc)2-PP-dolichol was isolated from Madin-Darby canine kidney cells. Treatment of these oligosaccharide lipids with a series of selected glycosidases led to the preparation of Man alpha 1,2Man alpha 1,2Man alpha 1,3[Man alpha 1,6(Man alpha 1,3)Man alpha 1,6]Man beta 1,4GlcNAc beta 1,4GlcNAc-PP-dolichol; Man alpha 1,2Man alpha 1,2Man alpha 1,3[Man alpha 1,6]Man beta 1,4GlcNAc beta 1, 4GlcNac-PP-dolichol; and Man alpha 1,6(Man alpha 1,3)Man alpha 1, 6[Man alpha 1,3]Man beta 1,4GlcNAc-beta 1,4GlcNAc-PP-dolichol. The preparation, isolation, and characterization of each of these lipid-linked oligosaccharide substrates are described. PMID- 1416021 TI - The development of high-performance liquid chromatographic analysis of allyl and allyloxycarbonyl side-chain-protected phenylthiohydantoin amino acids. AB - Ten phenylthiohydantoin (PTH) amino acids possessing allyl (Al) or allyloxycarbonyl (Aloc) side-chain-protecting groups have been characterized by high-performance liquid chromatography for use in Edman degradation sequence analysis. Optimized separation of side-chain-protected and -unprotected PTH amino acids was achieved on a C-18 reversed-phase column with a two-step gradient spanning 32 min. Five of the side-chain-protected amino acids [Cys(Al), Cys(Aloc), Lys(Aloc), Thr(Aloc), Tyr(Al)] were completely stable to the conditions of PTH derivatization, four [Asp(OAl), Arg(Aloc)2, Glu(OAl), Ser(Aloc)] were partially deprotected during PTH derivatization, and one [His(Aloc)] was completely deprotected during PTH derivatization. All allyl-based derivatives were well resolved from their side-chain-unprotected counterparts. Studies on the stability to piperidine treatment showed Asp(OAl), Cys(Al), Glu(OAl), Lys(Aloc), Thr(Aloc), and Tyr(Al), and possibly Arg(Aloc)2 and Ser(Aloc), to be suitable for peptide synthesis by 9-fluorenylmethoxycarbonyl (Fmoc)-based chemistry. Edman degradation of Al and Aloc side-chain-protected Conus geographus Lys9-alpha-conotoxin GI synthesized on 4-methylbenzhydrylamine copoly(styrene-1%-DVB)-resin demonstrated the usefulness of these derivatives for solid-phase preview sequence analysis. PMID- 1416022 TI - Two-dimensional differential scanning calorimetry: simultaneous resolution of intrinsic protein structural energetics and ligand binding interactions by global linkage analysis. AB - A general theoretical development for the design and analysis of two-dimensional thermal stability surfaces of proteins is presented. The surfaces are generated from multiple excess heat capacity profiles ( vs T) obtained at varying concentrations of an interacting ligand. The energetics of both the intrinsic protein stability and the protein-ligand interaction are simultaneously resolved by employing statistical thermodynamic models in global linkage analysis. This formalism allows resolution of the intrinsic protein folding-unfolding parameters (enthalpy, entropy, and heat capacity changes) as well as the ligand interaction parameters (binding stoichiometry, enthalpy, entropy, and heat capacity changes). The theory has been applied to the case of ribonuclease A and its interaction with cytidine-2'-monophosphate. The accuracy of the thermodynamic parameters obtained by this approach compares within error with those parameters that can be obtained by direct measurements. PMID- 1416023 TI - A solid-phase screen for protein kinase substrate selectivity. AB - Cassette mutagenesis was used to synthesize an Escherichia coli expression library of unique phosphorylation sites. The cassette encodes a central serine residue surrounded by every combination of Ala, Arg, Gln, Glu, Gly, and Pro residues over a 7-residue segment (a total of 6(7) approximately 2.8 x 10(5) sequences). The cassette was inserted into the gene of a suitable carrier protein and expressed in E. coli with the T7 expression system, and the resultant library was subjected to solid-phase protein phosphorylation assays on nitrocellulose filters. When the library was screened with TPK1 delta, the modified catalytic subunit of the Saccharomyces cerevisiae cAMP-dependent protein kinase, individual colonies that expressed substrates for this kinase were identified. By DNA sequencing through the cassette region of positive clones, the consensus recognition sequence for TPK1 delta was deduced and found to conform with the well-established substrate selectivity of its mammalian homolog (Arg-Arg-Xaa Ser). Because a large number of clones can be sequenced rapidly, and the positions of invariant residues composing a recognition site identified, this approach may be useful as a general screen of protein kinase substrate selectivity. PMID- 1416024 TI - A strategy for the mapping of N-glycans by high-pH anion-exchange chromatography with pulsed amperometric detection. AB - We have evaluated the high-pH anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) with respect to its suitability to establish a carbohydrate mapping database that would enable carbohydrate structural analysis by mere comparison of retention times. The suitability of HPAE-PAD for carbohydrate structural analysis was ascertained by validation experiments. The retention times of distinct N-glycans, prepared and measured on different days, were shown to be highly reproducible, with a coefficient of variation (CV) of less than 0.5%, requiring less than 100 pmol of N-glycan per injection for reliable measurements. Including appropriate internal chromatographic standards, such as (Neu5Ac)1, (Neu5Ac)2, (Neu5Ac)3, and Neu5Gc, the HPAE-PAD method fulfills the analytical requirements with respect to accuracy, precision, reproducibility, and sensitivity. The N-glycan mapping database was established, using two optimized linear gradients "S" and "A" for sialylated and asialo N-glycans, respectively. Approximately 100 different N-glycans of known structure, which have thus far been measured and characterized, have entered our Lotus 1-2-3 mapping database. The efficiency of the database for structural determinations was tested, using the N-linked carbohydrates isolated from rhuEPO, expressed in BHK cells. Nine different sialylated N-glycans of rhuEPO (BHK) could be assigned with a deviation of less than +/- 0.5%, using gradient S, and six of the eight asialo N-glycans of rhuEPO (BHK) detected with gradient A could be assigned with an accuracy of less than +/- 1%, three of them even with an accuracy of less than 0.1%, providing the reliability of the established HPAE-PAD mapping database. PMID- 1416025 TI - Boundary analysis in sedimentation transport experiments: a procedure for obtaining sedimentation coefficient distributions using the time derivative of the concentration profile. AB - A procedure is described for computing sedimentation coefficient distributions from the time derivative of the sedimentation velocity concentration profile. Use of the time derivative, (delta c/delta t)r, instead of the radial derivative, (delta c/delta r)t, is desirable because it is independent of time-invariant contributions to the optical baseline. Slowly varying baseline changes also are significantly reduced. An apparent sedimentation coefficient distribution (i.e., uncorrected for the effects of diffusion), g*(s), can be calculated from (delta c/delta t)r as [formula: see text] where s is the sedimentation coefficient, omega is the angular velocity of the rotor, c0 is the initial concentration, r is the radius, rm is the radius of the meniscus, and t is time. An iterative procedure is presented for computing g*(s)t by taking into account the contribution to (delta c/delta t)r from the plateau region to give (delta c/delta t)corr. Values of g*(s)t obtained this way are identical to those of g*(s) calculated from the radial derivative to within the roundoff error of the computations. Use of (delta c/delta t)r, instead of (delta c/delta r)t, results in a significant increase (greater than 10-fold) in the signal-to-noise ratio of data obtained from both the uv photoelectric scanner and Rayleigh optical systems of the analytical ultracentrifuge. The use of (delta c/delta t)r to compute apparent sedimentation coefficient distributions for purposes of boundary analysis is exemplified with an antigen-antibody system. PMID- 1416026 TI - Determining the effect of inducible protein phosphorylation on the DNA-binding activity of transcription factors. AB - Inducible phosphorylation or dephosphorylation of transcription factors is an important mechanism of signal-dependent gene regulation in eukaryotic cells. This paper describes a combination of techniques that can be used to study the effect of this covalent protein modification on the DNA-binding activity of transcription factors. The protein of interest is genetically tagged with oligohistidine to allow rapid purification on nickel-chelate columns after being transiently overexpressed in eukaryotic tissue culture cells. Phosphorylation dependent DNA-binding activity is determined in a blotting assay including an in situ dephosphorylation step. Studies on the protooncogene-encoded transcription factor c-Jun employing this assay revealed a TPA-inducible protein dephosphorylation event that strongly increases the DNA-binding potential of the protein. Our data confirm the results published recently by others and provide a rapid, efficient, sensitive, and well-controlled experimental system to analyze the phosphorylation-regulated modulations in the DNA-binding activity of transcription factors. PMID- 1416027 TI - Development of a radiometric spot-wash assay for squalene synthase. AB - The principle of selective elution from a solid phase has been exploited to develop an assay for the determination of squalene biosynthesis in rat liver homogenates. Using either [1-14C]isopentenyl diphosphate as a precursor for squalene or [2-14C]farnesyl diphosphate as a direct substrate of squalene synthase, the production of radiolabeled squalene is determined after adsorption of assay mixtures onto silica gel thin-layer chromatography sheets and selective elution of the diphosphate precursors into a solution of sodium dodecyl sulfate at alkaline pH. The use of [2-14C]farnesyl diphosphate, and of an endogenous oxygen consumption system (ascorbate/ascorbate oxidase) to prevent further metabolism of squalene, allows the method to be applied as a dedicated assay for squalene synthase activity. The assay has been developed in microtiter plate format and may be deployed either in a quantitative, low-throughout mode or in a qualitative, high-through-put mode. The latter is suitable for screening to aid in the discovery of new inhibitors of squalene synthase. PMID- 1416029 TI - Immunochemical detection of proteins and nucleic acids on filters using small luminescent inorganic crystals as markers. AB - A new luminescent marker for the immunochemical detection of proteins and nucleic acids on filters is reported. The label consists of inorganic crystals, generally called phosphors, with a particle size of 0.1-0.3 microns, stabilized in suspension with polycarboxylic acids and subsequently conjugated to immunoreactive macromolecules. Immunophosphor conjugates exhibit slowly decaying fluorescence that is strong and practically nonfading and not sensitive to quenching by water molecules. They are therefore suited for conventional fluorescence detection as well as for time-resolved detection. The lifetime of the phosphors was in the micro/milliseconds range upon excitation with ultraviolet light. Proteins or nucleic acids immobilized on nitrocellulose filters were detected immunochemically or by hybridization, using haptenized nucleic acid probes followed by immunochemical detection, respectively. The ultimate detection limit of proteins, using phosphor-labeled macromolecules including an immunochemical amplification step, was found to be 10 fg. The detection limit of nucleic acids was 300 fg for demonstration of hapten-labeled probes and 10 pg in hybridization formats with hapten-labeled probes. The sensitivity of methods using phosphor-labeled macromolecules was in all cases as good as or better than that of methods using alkaline phosphatase developed to NBT/BCIP. The use of immunophosphors for detection of proteins and nucleic acids on Western and Southern blots is demonstrated. Finally, the use of multiple phosphors with different kinetic and spectral characteristics for multiparameter studies is indicated. PMID- 1416028 TI - Preparation of iron-deficient tissue culture medium by deferoxamine-sepharose treatment and application to the differential actions of apotransferrin and diferric transferrin. AB - We have shown that triiodothyronine-dependent GH1 rat pituitary cell growth in serum-free defined culture required apotransferrin (apoTf) (D. A. Sirbasku, et al., Biochemistry 30, 295-304, 7466-7477, 1991). These studies were done in "low Fe" medium without Fe(III)/Fe(II) salts. Nonetheless, significant concentrations of iron may have been contributed by other components, making this medium unsuitable for study of the differential effects of apoTf and diferric transferrin (2Fe.Tf). Measuring residual iron in culture medium has been troublesome because the most sensitive method (i.e., atomic absorption) detected levels only in excess of 10 ng/ml and did not distinguish between the forms of iron present. To estimate the Fe(III) available to bind to apoTf, we developed a more sensitive and specific method. Urea-polyacrylamide gel electrophoresis (PAGE) separates apoTf, the two monoferric transferrins, and 2Fe.Tf. [125I]apoTf was incubated with medium, or components, and the formation of [125I]-2Fe.Tf was monitored by urea-PAGE/autoradiography. By this method, the concentration of Fe(III) in low-Fe medium was estimated at 8.4 to 20 ng/ml and the sources were identified. We next sought to remove the Fe(III). Standard chelators were ineffective or cytotoxic. In contrast, an affinity method with deferoxamine Sepharose depleted greater than or equal to 90% of the Fe(III). In this medium, apoTf and 2Fe.Tf showed differential effects with GH1 cells and with MCF-7, MTW9/PL2, an MDCK cells. With the methods described here, the effects of apoTf and 2Fe.Tf on growth can be studied separately. PMID- 1416030 TI - An ultraviolet-spectrophotometric method with 2-cyanoacetamide for the determination of the enzymatic degradation of reducing polysaccharides. AB - A rapid, facile, and sensitive uv-spectrophotometric assay has been developed for the determination of the enzymatic degradation of polysaccharides that generates reducing sugars. The assay was carried out with 2-cyanoacetamide in a single test tube. The solution was left at pH 9 by the addition of borate buffer within 5 min. Measurement of the reaction mixture at 274 nm allows a simple determination up to 600 mumol/liter of reducing sugars. The coefficient of variation was less than 2% on all measurements. The assay was developed with pectin and polygalacturonic acid from apples and has been compared with the Somogyi-Nelson method. The new assay was then exemplarily used for the determination of the enzymatic hydrolysis products of pectin from cotton. PMID- 1416031 TI - In vitro transcription by RNA polymerase II in extracts of Xenopus oocytes, eggs, and somatic cells. AB - We describe procedures for preparing extracts of Xenopus oocytes, eggs, and somatic cells that will accurately transcribe class II genes. A variety of viral and Xenopus promoters direct the accurate initiation of transcription by RNA polymerase II in these extracts. Optimal ionic conditions (100-200 mM KCl, 12 mM MgCl2), template concentration (20-40 micrograms/ml), incubation time (30-60 min), and temperature (25 degrees C) for class II gene transcription are described. PMID- 1416032 TI - Gas chromatography/mass spectrometry assays for the determination of debrisoquine and sparteine metabolites in microsomal fractions of rat liver. AB - Debrisoquine and sparteine are prototype substrates of a genetic deficiency in cytochrome P450-dependent drug metabolism. Sensitive assays of in vitro oxidation of sparteine and debrisoquine are required for evaluation of this polymorphism. The activities were measured by quantitative analysis of 2-dehydrosparteine and 4 hydroxydebrisoquine production, respectively, using capillary column gas chromatography coupled with mass selective ion detection. With a single extraction, separation of parent drug, metabolite, and a suitable internal standard was readily achievable. Time-dependent production of both metabolites could be detected from as little as 40 micrograms of microsomal protein. Both activities showed a maximal activity with a 240-min incubation period. The ability to simultaneously quantify the parent drug and its metabolite suggests it would also be useful for evaluation of in vivo metabolism. PMID- 1416033 TI - Ring test for low levels of N-(2-hydroxyethyl)valine in human hemoglobin. AB - Hemoglobin adducts are useful for the identification and quantification of electrophilic agents in vivo. A modified Edman degradation method has been extensively used for monitoring exposure to ethylene oxide through gas chromatographic-mass spectrometric measurements of hydroxyethyl adducts to the N terminal valines in hemoglobin. In a ring test, four laboratories using different versions of the method analyzed eight human globin samples with low adduct levels from ethylene oxide. Measurements of the same adduct by a radioimmunoassay were also included. Strong correlation between the measurements by the different laboratories shows that the method in principle works well. However, there were some systematic quantitative differences. PMID- 1416034 TI - Bioluminescence detection system of mutagen using firefly luciferase genes introduced in Escherichia coli lysogenic strain. AB - A rapid and convenient microbial sensing system for mutagens was developed based upon the induction of prophage from Escherichia coli lysogenic strain and bioluminescence. The system consisted of lysogenic E. coli encoding firefly luciferase genes and a photodetection system. Measurement of mutagen mitomycin C was achieved by measuring the luminescence intensity emitted from E. coli lysogenic strain for the recombinant phage in the presence of luminescence substrates. Approximately 1 h after addition of mitomycin C, the luminescence began to be observed, and 3 h after, it attained a level of 2 times greater than that of 1 h. Irradiation with ultraviolet light also produced light based on induction of phage from the E. coli lysogenic strain for the recombinant phage. On the other hand, when nonmutagenic toxic compounds like sodium azide were added to the reaction medium, luminescence was not observed. Mitomycin C could be detected within 1 h with this sensing system, at concentrations down to 10(2) ng/assay. PMID- 1416035 TI - Reversible potentiometric oxygen sensors based on polymeric and metallic film electrodes. AB - Various materials and sensor configurations that exhibit reversible potentiometric responses to the partial pressure of oxygen at room temperature in neutral pH solution are examined. In one arrangement, platinum electrodes are coated with plasticized poly(vinyl chloride) films doped with a cobalt(II) tetraethylene pentamine complex. For such sensors, potentiometric oxygen response is attributed to a mixed potential originating from the underlying platinum electrode surface as well as a change in redox potential of the Co(II)-tetren doped film as the complex binds oxygen reversibly. The response due to the platinum surface is prolonged by the presence of the Co(II)-tetren/PVC film. Alternately, thin films of metallic copper, electrochemically deposited on platinum and/or sputtered or vapor deposited on a single crystal silicon substrate, may be used for reversible oxygen sensing. The long-term reversibility and potentiometric stability of such copper film-based sensors is enhanced (up to 1 month) by preventing the formation of cuprous oxide on the surfaces via the application of an external nonpolarizing cathodic current through the working electrode or by specifically using sputtered copper films that have [100] preferred crystal structures as determined by X-ray diffraction. The implications of these findings in relation to fabricating analytically useful potentiometric oxygen sensors are discussed. PMID- 1416036 TI - Enzyme packed bed system for the on-line measurement of glucose, glutamate, and lactate in brain microdialysate. AB - Rapid measurement of glucose, glutamate, and lactate is important in understanding the dynamics of the energy balance of the brain. Glutamate is also the main excitatory neurotransmitter. A general immobilized enzyme-based flow injection assay system is described which uses oxidase and peroxidase enzymes to convert the analyte into an oxidized ferrocene species which is detected electrochemically by reduction. The enzymes glucose oxidase, glutamate oxidase, lactate oxidase, and horseradish peroxidase are immobilized with near 100% efficiency onto 10-microns tresyl-activated silica beads (1000- and 500-A pore size). The beads are slurry-packed into 2- x 20-mm columns to give beds for glucose, glutamate, or lactate which are stable for greater than 40 days. The flow injection assays described have detection limits from 1.8 to less than 20 pmol and have been configured to have linear calibration responses over the range of basal and stimulated levels of the three compounds found in 5-microL microdialysate samples from the rat striatum. The assays are used for automated on-line measurement of glucose, glutamate, and lactate in striatal microdialysate at 2.5-min intervals. PMID- 1416037 TI - Comparison of BaTiO3 optical novelty filter and photothermal lensing configurations in photothermal experiments. AB - Photorefractive BaTIO3 is used as an optical novelty filter to highlight the high spatial frequency components of the photothermal signal. A real-time phase grating recorded in BaTIO3 acts as a matched rejection spatial filter for the probe laser. This reduces the stationary background from the optical signals thereby increasing signal contrast ratios. Rejection of the monotonous stationary signal provides a powerful means of improving the photothermal signal. This paper describes the construction of this novel apparatus and the experiments performed in order to compare its performance with photothermal lensing results. A theory that explains photothermal signal filtering with BaTIO3 as an adaptive spatial frequency filter is presented. Results comparing the optical signals obtained in a photothermal lensing experiments and those obtained in the BaTIO3 optical novelty filter experiments are presented. The optical novelty filter signals demonstrate a remarkable improvement in the signal contrasts for moderate photothermal-induced phase shifts. PMID- 1416038 TI - Effect of aging the hollow cathode by sputtering on the analytical precision of the hollow cathode discharge emission source. AB - Sputtering changes the analytical performance of the hollow cathode as an emission source. Proper conditioning (aging) of the hollow with sputtering greatly improves precision. Conditioning decreases the blank emission signal and changes the shape of the hollow. Micrographs which show the evolution of the bottom of the hollow into a stable bulb shape are presented. The blank emission signal decreases with aging of the hollow and approaches a constant value when the hollow is properly conditioned. A short-term stability (n = 5) of approximately 1.8% RSD has been observed frequently. An average long-term stability over several days (n = 45) of 4.5% for Li and 3.5% for Na in the emission signal from microsamples (less than 50 nL) deposited in the hollow cathode discharge source is reported here. Instrumentation, operation, and sample preparation procedures are described. PMID- 1416039 TI - Capillary electrophoresis-electrospray mass spectrometry for the analysis of recombinant bovine and porcine somatotropins. AB - A Beckman P/ACE 2050 high-performance capillary electrophoresis (HPCE) instrument has been interfaced with a Vestec electrospray ionization (ESI) mass spectrometer for the analysis of recombinant proteins. Peak resolution is not compromised by coupling HPCE to an ESI mass spectrometer. Recombinant bovine and porcine somatotropins (rbSt and rpSt) were used as model proteins. The standard curve of the capillary zone electrophoresis (CZE) method with UV detection for the determination of rpSt is linear in the range of 7-300 fmol with theoretical plates of approximately 410,000 m-1. The relative standard deviation for the rpSt peak migration time is less than 1%. The multiply-charged ion clusters obtained in the CZE-ESI mass spectrum for a sample of rpSt ranged from mlz 1363.2 (the cluster with 16 charges) to 1982.5 (the cluster with 11 charges). The average molecular weights of 21,812.6 and 21,798.3 for a sample of rbSt and rpSt determined in this study were nearly identical to the theoretical values of 21,812.0 and 21,797.9, respectively. Detection limit of the CZE-ESI mass spectrometer is approximately 100 fmol. The CZE method separated mono- and dideamidated species and monoacetylated compounds while the ESI mass spectrometer detected an analogue and a truncated homologue of rpSt comigrating with the major peak. The presence of mono- and dioxidized homologues was also detected in the major peak of some rbSt and rpSt samples. These data clearly indicated that, individually, both CZE and ESI mass spectrometric methods could not detect all impurities. Coupling of the HPCE Instrument and the ESI mass spectrometer enhances analytical capabilities of both tools for rapid characterization of recombinant proteins. PMID- 1416040 TI - Organic ion imaging using tandem mass spectrometry. AB - A triple-quadrupole mass spectrometer has been interfaced with a wide-angle secondary ion microprobe. The combination permits acquisition of data necessary to determine the distribution of targeted organic analytes even in the presence of overwhelming isobaric interference. Micrographs generated from secondary ion intensity alone are compared to those generated using secondary ionization with tandem mass spectrometry (MS/MS), both for image reference and to show the improvement in image quality that can be attained when MS/MS is employed. Inhomogeneous mixtures of glycerol, KCl, and asparagine on 1-cm-diameter aluminum targets were used to demonstrate the instrument's selectivity. Secondary ions generated from samples of this system include isobaric 133Cs+ implanted from the primary ion beam, the 41K(+)-glycerol adduct, and protonated asparagine. PMID- 1416041 TI - Controlling solvent strength and selectivity in micellar liquid chromatography: role of organic modifiers and micelles. AB - Simultaneous enhancement in elution strength and selectivity which has been previously observed in micellar liquid chromatography (MLC) for a variety of compounds is further investigated. The reasons behind the occurrence of this unique phenomenon are studied, and the influence of micelles and organic solvents on elution strength and selectivity is discussed. A model is developed which explains the dependence of the solvation ability of organic solvents in MLC (represented by the solvent strength parameter, S, of solutes) and the degree of solute interactions with micelles. Whenever the difference in solvent strength parameter values of two solutes in micellar eluents, dS, is positive, maximum selectivity is observed at the weakest eluent strength. When dS less than 0, there exists an inverse relationship between retention and solvent strength parameter so that selectivity monotonically increases with volume fraction of organic solvent in micellar eluents. It is shown that usually there is no direct relationship between the solvent strength parameter in MLC and retention. As a result, selectivity enhancement due to an increase in the concentration of organic modifier (i.e. solvent strength) occurs frequently in MLC. Interestingly, for cases where selectivity decreases with an increase in organic modifier, simultaneous enhancement of selectivity and solvent strength can be observed by increasing micelle concentration. In a sense, the concentrations of organic modifier and micelles complement one another in improving selectivity at higher elution strengths. As a result of this unique phenomenon better separations in shorter analysis times can be observed. The mutual effects of micelles and organic modifier on one another would also require a simultaneous optimization of these two parameters. PMID- 1416042 TI - Chromatographic characteristics of surfactant-mediated separations: micellar liquid chromatography vs ion pair chromatography. AB - The effects of concentrations of organic solvent and surfactant on elution strength and selectivity in MLC and IPC are studied. It is observed that selectivity between most pairs of solutes used in this study increases in MLC and either decreases or passes through a minimum in IPC, with the volume fraction of organic modifier. In both MLC and IPC, selectivity varies with surfactant concentration; however, the overall variation in selectivity and elution order are more pronounced in MLC. The solvent strength decreases in IPC and increases in MLC as a result of an increase in surfactant concentration. An iterative regression design is used to predict the optimum mobile-phase compositions in terms of solvent strength and selectivity. The correlation between the predicted and measured chromatograms is excellent in MLC and poor in IPC. This is due to a more regular and reproducible retention behavior in MLC which greatly facilitates the development of robust methodologies. For a mixture of amino acids and peptides, a large retention gap between the first and the last eluting solutes is observed in IPC, which makes the use of organic solvent gradient inevitable. However, a better separation for the same mixture of solutes can be achieved in MLC isocratically. Apparently, the general elution problem can be alleviated in MLC by using an optimum eluent composition. It is observed that the efficiencies of MLC and IPC are comparable. The above observations indicate that MLC can be a powerful alternative to IPC in order to achieve optimized separations in shorter analysis time. PMID- 1416043 TI - Specific base recognition of oligodeoxynucleotides by capillary affinity gel electrophoresis using polyacrylamide-poly(9-vinyladenine) conjugated gel. AB - Poly(9-vinyladenine) was synthesized and utilized as an affinity macroligand entrapped within the gel matrix. Base-specific separation of oligodeoxynucleotides was achieved with high resolution and high speed by electrophoresis, using capillaries filled with conjugated polyacrylamide-poly(9 vinyladenine) gel. Oligothymidylic acids were selectively separated from the mixture of oligothymidylic and oligodeoxyadenylic acids by utilizing a specific hydrogen bonding between poly(9-vinyladenine) and oligothymidylic acids. Migration time and resolution of oligodeoxynucleotides were influenced by several parameters, such as the size of poly(9-vinyladenine), capillary temperature, and concentrations of poly(9-vinyladenine) and urea. Some guidelines are presented, based on the theoretical formulation of the effect of these parameters, in order to find optimum electrophoretic conditions. Analytical capillary affinity gel electrophoresis was developed for the selective and sensitive base recognition of oligodeoxynucleotides with efficiencies as high as several 10(6) plates/m by using a urea-gel capillary with poly(9-vinyladenine) and temperature-programming. PMID- 1416044 TI - Noninvasive imaging of nanogram quantities of DNA in agarose electrophoresis gels. AB - Image processing techniques which separate the DNA Kerr effect and induced electrokinetic distortion contributions to electric birefringence images of agarose nucleic acid electrophoresis gels are described. Under standard electrophoresis conditions, detection limits of 10 ng of DNA per well are obtained in hydroxyethylated agarose without signal averaging or 7.5 ng with averaging of four measurements. Maintaining constant gel temperature is shown to improve the quality of the images. Monochromatic light (589 nm) is shown to give a small increase in sensitivity compared to polychromatic (650 +/- 20 nm) light. PMID- 1416045 TI - Kinetic chromatographic sequential addition immunoassays using protein A affinity chromatography. AB - A new type of chromatographic immunoassay based on sequential addition is described. On a protein A column, the antibody, the sample containing the antigen, and then a known amount of antigen are sequentially injected. This assay is designed to shorten analysis times and reduce complexity of dual-column chromatographic immunoassays, circumvent desorption buffer interferences common to affinity chromatography, and eliminate the need for tagged molecules. This new technique is named kinetic immunochromatography sequential addition (KICQA). Because of its kinetic nature, flow rate will have a large effect on KICQA, and the impact of changing flow rate is studied extensively. By use of various amounts of antibody, the dynamic range of KICQA is shown to be selectable over 2.5 orders of magnitude. Finally, KICQA was used to determine transferrin and albumin in human serum. Both analytes show good agreement with their respective reference methods, and an albumin assay was performed in under 1 min. PMID- 1416046 TI - Real-time monitoring of DNA polymerase reactions by a micro ISFET pH sensor. PMID- 1416047 TI - Time-of-flight mass spectrometry with an electrospray ion beam. AB - An electrospray ionization source has been coupled to a reflection time-of-flight mass spectrometer. By orienting the ion source perpendicular to the field-free drift region, the longitudinal energy spread of the ion packet has been substantially reduced, allowing a mass resolving power of over 1000 to be achieved for both low-mass and high-mass ions of biological interest. In addition, instrument sensitivity allows the routine detection of low-picomole and subpicomole quantities of large multiply charged species such as cytochrome c (MW = 12,360.9). The potential utility of this instrument for conducting rapid screening of chromatographic effluents is discussed in light of its simplicity, rapid scanning speed, and high sensitivity. PMID- 1416048 TI - Separation and identification of carotenoids and their oxidation products in the extracts of human plasma. AB - Eighteen carotenoids as well as vitamin A and two forms of vitamin E (gamma- and alpha-tocopherol) have been separated from extracts of human plasma by high performance liquid chromatography (HPLC) on reversed-phase and sillca-based nitrile-bonded columns. In the order of chromatographic elution on a C18 reversed phase column, the carotenoids were identified as (3R,3'R,6'R)-beta, epsilon carotene-3,3'-diol [(3R,3'R,6'R)-lutein], (3R,3'R)-beta, beta-carotene-3,3'-diol [(3R,3'R)-zeaxanthin], 5,6-dihydroxy-5,6-dihydro-psi,psi-carotene, 3-hydroxy 2',3'-didehydro-beta,epsilon-caroten-3-ol, 3-hydroxy-beta-carotene,psi,psi carotene, 7,8-dihydro-psi,psi-carotene, beta,psi-carotene, 7,8,7',8'-tetrahydro psi,psi-carotene, beta,epsilon-carotene, beta,beta-carotene, 7,8,11,12,7',8' hexahydro-psi,psi-carotene, and 7,8,11,12,7',8'-11',12'-octahydro-psi,psi carotene. The polar carotenoids, which eluted in the vicinity of lutein and were unresolved on the C18 column, have been separated on a nitrile-bonded column employing isocratic HPLC conditions. In the order of elution, the carotenoids were epsilon,epsilon-carotene-3,3'-dione, 3'-hydroxy-epsilon,epsilon-caroten-3 one, 5,6-dihydroxy-5,6-dihydro-psi,psi-carotene, 3-hydroxy-beta,epsilon-caroten 3'-one, (all-E,3R,3'R,6'R)-lutein, (all-E,3R,3'R)-zeaxanthin, and (all E,3R,3'S,6'R)-beta,epsilon-carotene-3,3'-diol (3'-epilutein) followed by several geometrical isomers of lutein and zeaxanthin. PMID- 1416049 TI - DNA sequencing using capillary array electrophoresis. AB - A DNA sequencing method is presented that utilizes capillary array electrophoresis, two-color fluorescence detection, and a two-dye labeling protocol. Sanger DNA sequencing fragments are separated on an array of capillaries and detected on-column using a two-color, laser-excited, confocal fluorescence scanner. The four sets of DNA sequencing fragments are separated in a single capillary and then distinguished by using a binary coding scheme where each fragment set is labeled with a characteristic ratio of two dye-labeled primers. Since only two dye-labeled primers are required, it is possible to select dyes that have identical mobility shifts. It is also shown that the ratio of the signal in the two detection channels provides a reliable identification of the sequencing fragment. DNA sequencing results on a 25-capillary array are presented. PMID- 1416051 TI - Ross receives Wiley Award. PMID- 1416050 TI - Drug of abuse confirmation in human urine using stepwise solid-phase extraction and micellar electrokinetic capillary chromatography. AB - This paper demonstrates that most common drugs of abuse can be absorbed simultaneously onto a mixed-mode bonded-phase matrix and eluted sequentially in two to three steps for subsequent analysis by micellar electrokinetic capillary chromatography (MECC). Having on-column multiwavelength UV absorption detection, this is shown to be an attractive approach for confirmation testing of barbiturates, hypnotics, amphetamines, opioids, benzodiazepines, and metabolites of cocaine in a single aliquot of human urine. For these compounds, no hydroysis of the urine specimen or sample derivatization is required. Under the examined conditions using 5 mL of urine, excellent recoveries (80-90% level) and detection limits (about 100 ng/mL) are obtained. For patient urines which tested positively for different classes of drugs using immunological screening methods, a two-step extraction scheme is shown to provide extracts suitable for rapid MECC confirmation of the drugs of abuse. PMID- 1416052 TI - [In memoriam: Prof. Dr. med. Otto Bucher (1913-1991)]. PMID- 1416053 TI - Immunohistochemistry for intermediate filaments in the enteric nervous system of the porcine small intestine. AB - Antibodies against the cytoskeletal neurofilament protein 200 and gliafilament acidic protein were used for an immunohistochemical staining of nerve and glia cells in porcine small intestine. In sections as well as in whole mount preparations, the morphological and topographical features of the enteric nerve plexus could be demonstrated. The enteric glia cells are characterized by an abundance of immunoreactive GFAP, which allows a subsequent staining of the plexus. NFP 200 is immunohistochemically recognized only in a part of the neurons. This immunoreactive neuronal population can be identified morphologically as Typ II-neurons, which are defined as adendritic and pseudouniaxonal to multiaxonal. The immunostaining of intermediate filaments is an easy and reproducible means for studying the enteric nervous system and invaluable for the histopathological diagnosis of its morphological abnormalities. PMID- 1416054 TI - Lectin binding pattern in human retinal pigment epithelium. AB - A comparative lectin histochemical study of human retinal pigment epithelium (RPE) was performed to investigate the lectin binding pattern of normal, reactive and proliferating RPE. Normal RPE with attached sensory retina was found to bind the lectins Con A, WGA, PNA and RCA I. Reactive and proliferating RPE in retinal detachment and in photocoagulation scars revealed the same lectin binding pattern although its cellular topography changed. RPE-macrophages showed an additional reaction with SBA. In periretinal membranes of human PVR the typical lectin binding pattern of Con A, WGA, PNA and RCA I was found in pigmented and in a subpopulation of non-pigmented cells, suggesting that these lectin-positive elements were of RPE-origin. Additionally, single pigmented cells positive for SBA were found indicating macrophage differentiation. Thus lectin histochemistry provides a tool for cytochemical identification of RPE and its morphologic variants by revealing a specific combination of sugar-binding sites. PMID- 1416055 TI - Morphological variants of the suprapatellar bursa. AB - Two hundred and ten specimens were examined anatomically to study the different shapes of the suprapatellar bursa. It is possible to classify the morphologic variants of the suprapatellar bursa into three types. A bursa not subdivided was found in 83% and named Type A. A bursa subdivided by a vertical septum at the lateral side of the suprapatellar bursa was seen in 17% of the knee joints. The vertical septum was complete in 9% (Type B), incomplete in 8% (Type C) of the cases. It separated the bursa into a main medial part and a small lateral saccular space. There was no corresponding subdivision at the medial side. A space proximal to the suprapatellar bursa was found in two cases. PMID- 1416056 TI - Fine structure of the dorsal lingual epithelium of the domestic, newborn kitten, Felis catus. AB - The tip and the body of the tongue of the domestic kitten, Felis catus, were examined by light and transmission electron microscopy. On the tip of the tongue, no filiform papillae were observed, but the connective tissue papillae of the lamina propria were recognized. On the lingual body, there were filiform papillae composed of an anterior, a posterior and interpapillar epithelium. Under the transmission electron microscope, the epithelium on the tip of the kitten tongue was found to be of the stratified squamous type. The epithelium contained no cells filled with keratin fibers. In the lingual body, the interpapillar epithelium contained very few keratohyalin granules, and no cells with keratin fibers. In the epithelium on the anterior side of the filiform papillae, numerous keratohyalin granules appeared in the intermediate layer. In the surface layer, a thin layer of typical keratinized cells was visible. In the epithelium on the posterior side of the filiform papillae, a thick layer of keratinized cells was located on the surface layer. PMID- 1416057 TI - Prenatal influence of alcohol following a single exposure in two inbred strains of mice. AB - The effect of a single dose of ethanol on embryonic development was investigated in two inbred strains of mice. Ethanol (25% v/v solution, 0.02 ml/g body weight) was administered intraperitoneally on either gestational day 6, 9 or 12 to C57BL/6J and DBA/2J mice. All fetuses recovered near term were alive and appeared normal. The incidence of fetal death was not affected. Fetal weight was significantly reduced in the C57BL/6J strain of mice. Maternal exposure to a single and moderate dose of ethanol did not have any profound effect on the conceptus. For the development of laboratory models to mimic fetal alcohol effects in humans, the selection of appropriate genotype is important. PMID- 1416058 TI - Embryonic development in the chick following exposure to ethanol, acetaldehyde and cyanamide. AB - The influence of cyanamide, an inhibitor of aldehyde dehydrogenase, on the embryopathic effects of ethanol and acetaldehyde, was investigated in the chick embryo. Both ethanol and cyanamide significantly increased embryonic mortality, but did not affect embryonic growth, compared to treatment with either ethanol or cyanamide. Acetaldehyde combined with cyanamide increased embryonic mortality and retarded embryonic growth. Cyanamide influence on embryonic development was minimal. The extent of acetaldehyde involvement in ethanol teratogenicity remains unclear from the present findings. PMID- 1416059 TI - Anomalous course of the median nerve medial to the trochlea and anterior to the medial epicondyle of the humerus. AB - It is generally assumed that in the cubital region the median nerve is directly medial to the brachial artery and that it lies anterior to the trochlea of the humerus, from which it is separated by the brachialis muscle. Three instances are noted where the median nerve passed medial to the trochlea and anterior to the medial epicondyle, deep to the pronator teres, unilateral in one subject and bilateral in another. Its possible significance in elbow trauma is commented upon. PMID- 1416060 TI - Human doubled renal and testicular arteries. AB - Doubled renal and testicular arteries were found in a well-developed 69-year-old caucasian male. The right kidney had two renal arteries, one at its usual midorgan (hilar) position and one inferior polar. One testicular artery arose from the mid-point of the usual renal artery, passed under the renal vein at its junction with the inferior vena cava, and then crossed over the inferior polar renal artery. The second testicular artery arose from the inferior polar renal artery near its origin from the abdominal aorta. The two testicular arteries remained doubled throughout their course and both entered the right testis at separate sites on the organ. The inferior vena cava passed under the inferior polar and over the superior testicular artery and the superior renal artery. PMID- 1416061 TI - [A rare variation in the zone of the carotid artery]. AB - An extremely rare variation in the angioarchitecture of the carotid arteries consists in the complete missing of the right common carotid artery. The brachiocephalic trunc (innominate artery), forming a bulbus-like extension, branches out into three major stems: internal carotid artery, external carotid artery and the right subclavian artery. The variation is embryologically explainable: The aortic arches III and IV arise together (without ventral aortic root between them) from the persisting initial segment of the right ventral aorta. PMID- 1416062 TI - Bending strength of upper canine tooth in domestic dogs. AB - The bending strength of the upper canine tooth is analyzed on 51 domestic dogs of various breeds. Data show that canine tooth length is greater among small domestic dogs when compared to small wild dogs, and large wild dogs when compared among large domestic dogs. Tooth strength is also greater among small domestic dogs and large wild dogs. The greater tooth strength of the small domestic dogs may be attributed to the idea that small domestic dogs are closer in ancestry to the grey wolf (Canis lupus) than are small wild canids. Skull foreshortening and tooth strength appear to be correlated in the canidae. PMID- 1416064 TI - Stability of neuron number in the lateral part of the nucleus of the solitary tract in the ageing mouse brain. AB - Neuron number was estimated in the lateral part of the nucleus of the solitary tract of the mouse brain at 6, 15, 22, 25, 28 and 31 months of age. There was no significant variation in neuron number with age with an overall mean of 8500. PMID- 1416063 TI - [Fine structure of the raphe nuclei of sheep and goats]. AB - The medullary raphe system of sheep and goat can be divided in the solitary nuclei raphe magnus and pallidus besides the impaired Nucleus raphe paramedianus. The nucleus raphe magnus begins in the caudal end of the medulla oblongata running far to the pons. On the other hand you can follow the nucleus raphe pallidus and paramedianus only in distinct area near the obex. Different types of neurons are isolated and described in light- and electronmicroscopical investigations. All three nuclei are poor of synapses. PMID- 1416065 TI - Stability of neuron number in the ageing mouse paraventricular nucleus. AB - The number of neurons in the paraventricular nucleus was estimated in brains from male mice aged 6, 25, 28 and 31 months. There was no significant variation with age in neuron number (mean 2715). At all ages most neurons were parvocellular neurons and the neurosecretory magnocellular neurons made up only 10% of the total. There was no significant variation in neuronal nuclear diameter (mean 9.4 microns) with age. The nuclear diameter of both parvocellular and magnocellular neurons was identical. The difference in size between the two types of neurons was due to the difference in volume of their perikarya. PMID- 1416066 TI - Immunohistochemical localization of relaxin in the reproductive system of the female opossum (Didelphis virginiana). AB - Relaxin-immunoreactivity was demonstrated in the cytoplasm in the luteal cells from pregnant and lactating opossums. Immunoreactivity for relaxin was not demonstrated elsewhere in the ovary, in the reproductive tract or in the placenta. The corpus luteum is thought to be the primary source of relaxin in Didelphis and in this regard is similar to several eutherian mammals including man. PMID- 1416067 TI - Ultrastructure of the exocrine pancreas in the snake Waglerophis merremii (Wagler). AB - Three types of serozymogenic cells were found in the secretory compartment of the snake exocrine pancreas. Type I cell was the most common and presented a well developed granular endoplasmic reticulum arranged in cisternal and vesicular forms. The cisternal form was located predominantly in the basal regions of the cell and the vesicular form was found in the supranuclear regions of the cell next to a prominent Golgi complex. Mature secretory granules were seen at the cell apex. The cytoplasmic matrix of the Type II cells was electron dense but had only poorly-developed organelles. Secretory granules were rare. The cytoplasmic matrix of the Type III cells was electron lucent and the granular endoplasmic reticulum in the cisternal form was located predominantly in the supranuclear region, whereas the vesicular form was randomly distributed throughout the cytoplasm. The nucleus appeared pale due to the fine dispersion of the chromatin; the nucleolus was prominent. Centroacinar and intermediate cells were also examined. PMID- 1416068 TI - An HRP study of the location of the motoneurons supplying the tensor veli palatini muscle of the rabbit. AB - Location of the motoneurons supplying the tensor veli palatini muscle of the rabbit was examined with the retrograde labeling technique following intramuscular injection of HRP. Labeled motoneurons were ipsilaterally located in the ventral or ventromedial portion of the rostral two-thirds of the motor trigeminal nucleus at the level of about 6.0 to 8.5 mm rostral to the obex. The location of the labeled motoneurons was ventromedial to the region supplying the masseter, the temporalis, and the medial pterygoid muscles and ventral to the region supplying the anterior digastric and the mylohyoid muscles, the location which coincided with the lateral pterygoid region. The labeled motoneurons were scattered around or in this region. PMID- 1416069 TI - Differentiation of oxytalan fibres from elastic fibres with reagents for detection of magnesium. AB - Elastic fibres in various human and animal tissues revealed positive results with reagents for the detection of magnesium. By contrast, no Mg could be detected in oxytalan fibres or in zonular fibres of the ciliary body, which are composed of microfibrils not containing elastin. Mg is therefore concluded to be associated with the elastin core of elastic fibres. Its antagonism to calcium is speculated to play a protective role in maintaining the extensibility of elastin. PMID- 1416070 TI - [History of classification systems of conjoined twins by specific consideration of the classification systems of Louis Bolk (1866-1930)]. AB - Classification systems concerning conjoined twins have been developed in the nineteenth century by many authors, a.o. J. F. Meckel (1816), I. Geoffroy Saint Hilaire (1832), E. F. Gurlt (1831), Fr. Ahlfeld (1880), C. Taruffi (1881), and in the beginning of the twentieth century, a.o. J. W. Ballantyne (1902) and E. Schwalbe (1907). However, these classification systems were very complex and mainly based on the external morphology of the conjoined twins. In contrast to many other classification systems the professor in Anatomy at the University of Amsterdam Louis Bolk divided conjoined twins in only three main groups: 1 greater than diplopagi simplex caudad; 2 greater than diplopagi simplex craniad; 3 greater than diplopagi simplex mesad. The last group was divided into ventrad and laterad conjuncti. For the study of conjoined twins the Vrolik Collection and many other specimens of the Museum of the Department of Anatomy and Embryology of the University of Amsterdam were very important for Bolk. Three factors were the main reason that the concept of the classification of double monsters of Bolk has not been cited often in the international literature: 1 greater than the publications of the classification in a national journal in Dutch; 2 greater than the coincidence of the publication of E. Schwalbes famous handbook "Die Morphologie der Missbildungen des Menschen und der Tiere II. Die Doppelbildungen" in the same period and 3 greater than the problem that the verification of the classification, mainly based upon morphogenesis, has not been possible because of technical problems in performing these experiments in mammals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416071 TI - Distribution of type I collagen, type II collagen and PNA binding glycoconjugates during chondrogenesis of three distinct embryonic cartilages. AB - Previous studies of chondrogenesis have been focused on limb bud cartilage, whereas little is known about chondrogenic processes of other cartilages with different developmental fates. We hypothesize that cartilages with various developmental fates might show identical characteristics of chondrogenesis. The chondrogenic processes in the nasal septum, the mandible, and the limb bud of the mouse were examined by means of PNA-binding glycoconjugate, and types I and II collagen expression. Swiss-Webster mouse embryos of 11 days (E11) to 14 days (E14) gestation were fixed and processed for immuno- and lectin histochemistry. The blastema of mesenchymal cell aggregates stained positively with anti-type I collagen, but very weakly with anti-type II collagen in all three models at E12, whereas PNA bound to the blastema in the limb bud but not in nasal septum or mandible. Types I and II collagens coexisted in cartilages at E13. Type II collagen was predominant in E14; type I collagen was confined to the peripheral region. The synchronized transitional expression of the collagen phenotypes in all three embryonic cartilages may be systemically regulated. The presence or absence of the PNA-binding glycoconjugates may be involved in characterizing the nature of the cartilages. PMID- 1416072 TI - Cholinergic and non-cholinergic neurons in the rat pedunculopontine tegmental nucleus. AB - Choline acetyltransferase immunhistochemistry was employed at light and electron microscopic levels in order to determine the distribution of cholinergic neurons in two subdivisions of the rat pedunculopontine tegmental nucleus that were previously defined on cytoarchitectonic grounds, and to compare the synaptic inputs to cholinergic and non-cholinergic somata in the subnucleus dissipatus, which receives major input from the substantia nigra. Large cholinergic neurons were found in both the pars compacta and the pars dissipata of the pedunculopontine nucleus. However, they were intermingled with non-cholinergic neurons and did not respect the cytoarchitectural boundaries of the nucleus. Ultrastructural study showed that all cholinergic neurons in the subnucleus dissipatus exhibited similar features. The majority had large somata (largest diameter greater than or equal to 20 microns) containing abundant cytoplasmic organelles and nuclei displaying a few shallow invaginations. Synaptic terminals on the cholinergic cell bodies were scarce and unlabeled boutons containing spherical synaptic vesicles and establishing asymmetric synaptic junctions were the dominant type. In contrast, the non-cholinergic neurons presented prominent differences in the size of their somata as well as in the distribution of axosomatic synapses. Two almost equally represented classes of non-cholinergic neurons which are referred to as large (largest diameter greater than or equal to 20 microns) and small (largest diameter less than 20 microns) were recognized. Large non-cholinergic cell bodies were ultrastructurally similar to the cholinergic ones, but they received rich synaptic input by unlabeled nerve terminals which contained pleomorphic vesicles and were engaged in symmetric synaptic junctions. Small non-cholinergic cell bodies were characterized by deeply invaginated nuclei surrounded by a narrow rim of cytoplasm, and were often found near or in direct apposition to the cholinergic somata. Their major input consisted of axosomatic boutons containing round synaptic vesicles. These results demonstrate that cells in the pedunculopontine tegmental nucleus are differentiated with regard to their axosomatic synaptic inputs which may influence their firing properties. Furthermore, they support previous suggestions that nigral afferents may be preferentially distributed to a subpopulation of the pedunculopontine neurons. PMID- 1416073 TI - Mast cell populations in the chick embryo lung and their response to compound 48/80 and dexamethasone. AB - Two mast cell populations, connective tissue mast cells (CTMCs) and mucosal mast cells, (MMCs) containing different proteoglycans in their granules, can be distinguished in several animal species by means of histochemical methods. In this study we documented the presence of these two types of mast cell in the chick embryo lung, from the 15th incubation day for the MMCs, and from the 18th incubation day for the CTMCs. Lungs of embryos treated with compound 48/80, which produces degranulation of the CTMCs, showed a decrease in the number of this type of mast cell and an unchanged number of MMCs. In the lungs of embryos treated with dexamethasone, which degranulates MMCs, a reduction in the number of these cells and an unchanged number of the CTMs were found. PMID- 1416074 TI - Laminar distribution and morphology of NADPH-diaphorase containing neurons in the superior colliculus and underlying periaqueductal gray of the rat. AB - We have studied the laminar distribution of reduced nicotinamide dinucleotide phosphate diaphorase (NADPH-d) activity and the morphology of positive neurons in the superior colliculus (SC) and the underlying periaqueductal gray (PAG) of the rat. The morphology of NADPH-d-positive neurons has been compared to that of Golgi-impregnated cells. The highest activity occurs in the stratum zonale and stratum griseum superficiale, contrasting with the pale neuropil in the stratum opticum, where only a few positive neurons are found. In the stratum griseum intermedium positive neurons are grouped in patches separated by narrow, NADPH-d negative bands. In the deeper layers, the neuropil is NADPH-d-negative, and few neurons show enzymatic activity. In contrast, numerous neurons in the dorsolateral part of the PAG are intensely positive. They are continuous with the positive neurons in the stratum album profundum, with no clear border between the two centers. In both SC and PAG, only small and medium sized neurons are NADPH-d positive. In comparison with Golgi material, all types of small neurons in the superficial layers show NADPH-d activity; NADPH-d histochemistry, however, does not visualize the characteristic dendritic appendages of these neurons. The large neurons of the SC and PAG, probably representing the long-projecting neurons of these centers, do not contain the enzyme. PMID- 1416075 TI - Late postnatal development and differentiation of the ductus epididymidis in a dasyurid marsupial (Antechinus stuartii). AB - The general histology and ultrastructural features of the developing ductus epididymidis were examined in the brown marsupial mouse, Antechinus stuartii, from April, when males were sexually immature, until August, when the adult males were involved in mating activities, just prior to the annual male die-off. Samples were also examined 3 and 6 months after the August die-off period in males kept in isolation from conspecifics during the prebreeding and breeding periods. In April, tubule diameter and epithelial height were largest in the caput and least in caudal segments but the reverse was observed thereafter. Epithelial height increased in caput segments in August and remained high in the post die-off samples. However, caput epithelial height and tubule diameters were low compared with the remainder of the duct from July until February. Luminal shape in caudal segments (10, 11 and 12) changed in June from circular to a narrow slit, and the epithelium became variable in height. The epididymal epithelium was undifferentiated with few cytoplasmic organelles in April. Differentiation occurred mostly from May to June in association with an increased abundance of cytoplasmic organelles, increasing prostatic weight and rising plasma androgen levels. Differentiated principal and basal cells were found in caput and corpus regions in May and in caudal segments in June in association with the de novo development of a brush border of microvilli. Few clear cells were seen in caput and corpus regions of the duct in May but they, and mitochondria-rich cells, were common throughout the duct from June. Development of the unusual structural features of the cauda epididymidis preceded the arrival of spermatozoa in June. The presence of degenerating spermatozoa and cytoplasmic droplets in the cauda at this time suggested that it was not yet capable of supporting sperm viability. There was no evidence to suggest that the presence of spermatozoa has a stimulatory effect on the epididymis. Intact sperm were observed throughout the duct from July. Free cytoplasmic droplets, which showed some evidence of degeneration, collected in large masses in the distal corpus/proximal cauda epididymidis of adult males between aggregates of spermatozoa. Epididymal differentiation appeared complete by mid-July; few ultrastructural changes occurred after this time. Recruitment of spermatozoa into the epididymis ceased by August and was associated with a rapid decline in sperm content in the proximal caput segments. In the November and February samples, spermatozoa were present only in distal corpus and proximal cauda segments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1416076 TI - Fetal antigen 2 (FA2) in human fetal osteoblasts, cultured osteoblasts and osteogenic osteosarcoma cells. AB - Immunohistochemical staining techniques used on an 11-week-old fetus showed that fetal antigen 2 (FA2) was present intracellularly in endochondral and perichondral osteoblasts, and the immunoreaction was extended into the adjacent bone matrix. Osteoclasts and chondroblasts were found to be FA2 negative. A granular perinuclear intracytoplasmic FA2 immunoreaction was found in cultured osteoblasts and osteogenic osteosarcoma cells, and immunoelectron-microscopical examination revealed a granular immunoreaction product in the rough endoplasmic reticulum. These findings indicate that FA2 is synthesized by osteoblasts and osteogenic osteosarcoma cells. A reaction of immunological identity was found between FA2 purified from second trimester amniotic fluid and serum-free supernatants of cultured osteogenic osteosarcoma cells. This shows that an antigen recognized by the anti FA2 antibody is secreted by these malignant cells. Thus, FA2 may represent a marker for altered bone metabolism, and have a potential in the classification of osteogenic osteosarcoma/chondrosarcoma. PMID- 1416077 TI - Histochemical distribution of zinc in the brain of the rainbow trout, Oncorhynchos myciss. II. The diencephalon. AB - The distribution of zinc in the diencephalon of the rainbow trout, Oncorhynchos myciss, is described in the present paper, which is the second in a series of three reporting for the first time the distribution of a heavy metal in the fish brain. The Neo-Timm method was used for the histochemical demonstration of zinc. The staining was essentially confined to the neuropil, in all probability representing stained axon terminals, but stained nerve cell bodies were observed in the nucleus lateralis geniculatus and the nucleus cerebellosus hypothalami. Stained fibers were never seen. The staining gave rise to a consistent, specific distribution pattern, which accorded well with the diencephalic nuclei defined on the basis of cytoarchitectural criteria. The diencephalon was in general stained with much higher intensity than the telencephalon, in surprising contrast to the state of affairs in the mammalian, reptilian, and avian brain. In species of these classes, high staining intensities are observed almost exclusively in the telencephalon. The Neo-Timm staining was predominantly distributed in the nuclei of the periventricular zone, but some internal (migrated) nuclei did show a positive staining reaction, namely the nucleus lateralis geniculatus, the anterior thalamic nucleus, the nucleus diffusus tori lateralis, and the nucleus cerebellosus hypothalami. The zinc distribution pattern has been compared with the terminal fields of afferent projections, known from experimental studies, and with the distribution of substance P. The possible function of zinc in synaptic vesicles is considered. PMID- 1416078 TI - The relationship between the number of nuclei of an osteoclast and its resorptive capability in vitro. AB - This study examined the relationship between the number of nuclei in an osteoclast and its resorptive efficiency, as demonstrated by the size of the pit it can make in a mineralized tissue in 24 h in vitro. Osteoclasts released mechanically from prehatch chick long bones were cultured on dentine slices or on plastic dishes for periods of 6 or 24 h. The frequency distribution of the multinucleate tartrate-resistant acid phosphatase (TRAP)-positive cells with different numbers of nuclei was determined: the mean number of nuclei per cell was 6.92, with a mode of 4.47% had 5 or fewer nuclei and only 11% more than 10 nuclei. The pits associated with 292 osteoclasts with known numbers of nuclei were measured using a confocal laser light microscope (Lasertec) and dedicated image analysis system, and depths, plan areas and volumes determined. There was a positive correlation between the number of nuclei per osteoclast and the volume of the pit made, but a trend for the volume resorbed per nucleus to decrease with increase in the number of nuclei per osteoclast. PMID- 1416079 TI - Superfluousness of motor innervation for the formation of muscle spindles in neonatal rats. AB - Muscle spindles form de novo in reinnervated muscles of neonatal rats treated with nerve growth factor. Whether the spindles can also form in muscle reinnervated only by afferents was investigated by removing the lumbosacral segment of the spinal cord immediately after crushing the nerve to the medial gastrocnemius muscle at birth, and administering nerve growth factor for 10 days afterwards. As predicted, the medial gastrocnemius muscles were reinnervated by afferents, but not efferents. No motor endplates were visible on any muscle fibers, and extrafusal fibers were atrophied. The reinnervated muscles contained spindle-like encapsulations of one to four fibers at 5, 7, 9 and 30 days after the nerve crush. The number of spindles as well as encapsulated fibers exceeded that of normal medial gastrocnemius muscles. The encapsulated fibers resembled typical intrafusal fibers. They had normal sensory-muscle contacts, but no motor endings. The fibers displayed equatorial clusters of myonuclei and expressed the spindle-specific slow-tonic myosin heavy chain isoform at postnatal day 30. Thus, efferents are not essential for the formation and differentiation of muscle spindles in reinnervated muscles of neonatal rats. PMID- 1416081 TI - A scanning electron microscopic study on the distribution of peritubular dentine in cheek teeth of Cervidae and Suidae (Mammalia, Artiodactyla). AB - Distribution of peritubular dentine was studied in cheek teeth of fallow deer (Dama dama), roe deer (Capreolus capreolus) and wild boar (Sus scrofa). In the two cervid species, especially intense peritubular dentine formation was found in the outer regions of mid and cuspal coronal dentine. In these areas a marked asymmetry occurred, peritubular dentine being predominantly secreted onto the side of the dentinal tubule walls nearest to the dentinoenamel junction. Intensity and asymmetry of peritubular dentine formation decreased cervically. In root dentine, the walls of the dentinal tubules were covered with only a thin peritubular dentine layer of even thickness. Here, in contrast to peripheral coronal dentine, the volume of intertubular dentine far exceeded that of peritubular dentine. In porcine coronal dentine, PTD asymmetry, being of lesser extent than in cervids, was observed only in peripheral areas of cuspal and flank regions of the cheek teeth. Because peritubular is more highly mineralized than intertubular dentine, the relative volume of dentine made up from the two components has an important influence on dentinal wear resistance. The significance of variations in volume and distribution of peritubular dentine between different dentinal regions for achieving and maintaining a functional occlusal surface is shown for cervid cheek teeth. Our results suggest that dentinal structure (in addition to enamel structure) should be taken more into consideration when discussing occlusal surface morphology in herbi- and omnivores from a functional point of view. PMID- 1416080 TI - Schwann cells are not required for guidance of motor nerves in the hindlimb in Splotch mutant mouse embryos. AB - The topogenesis of the hindlimb nerves of Splotch homozygous mutant mouse embryos was studied using light and electron microscopy. Homozygous mutants show multiple defects of neural crest-derived tissues. The defects increase along a rostro caudal gradient. The cervical and upper thoracic segments have small spinal ganglia, and Schwann cells are associated with the spinal nerves. In the lumbo sacral region neurulation is not complete, and the derivatives of the neural crest are missing. The lumbo-sacral nerve trunks are formed by ventral roots only. They are occasionally associated with presumptive glial cells that have migrated from the spinal cord for a short distance. Beyond the vertebral primordia, the spinal nerves are not accompanied by Schwann cells. No compartmentalization of the axons within the lumbo-sacral nerves was visible, whereas Schwann cells did segment the nerve into the fascicles in brachial nerves. The lumbo-sacral plexus develops, and its branches grow into the hindlimb despite the absence of Schwann cells. On day 13.5 of gestation, the lumbo-sacral nerve trunks extend well into the distal calf. They are topographically correctly positioned. Their branches enter the muscle primordia and form contacts with their mesenchymal cells though the cutaneous branches are missing. Generally, the outgrowth of lumbo-sacral nerves is slower than in phenotypically normal littermates, whose nerves reach the foot plate at corresponding stages of development. These results demonstrate that the lumbo-sacral plexus and the topographically correct position of lumbo-sacral nerve trunks develop despite the absence of Schwann cells. Therefore Schwann cells are not necessary for the outgrowth and guidance of axons within the limb. PMID- 1416082 TI - Ultrastructural study of postnatal development of the tonsillar crypt epithelium of the musk shrew, Suncus murinus. AB - An ultrastructural study was made of the postnatal development of the tonsillar crypt epithelium in the musk shrew, Suncus murinus. On day 3 after birth, a particular kind of large lymphoid cell was first seen to move through the basement membrane into the epithelium. The next migration was that of lymphocytes, which passed through holes in the basement membrane. On days 5 to 7, the lymphocytes formed clusters, and pale epithelial cells of low electron density appeared. The cell clusters and pale epithelial cells fused on day 10. By day 14, these epithelial cells extended cytoplasmic projections to the surface of the epithelium, which had many heterophagic vacuoles and some microvilli-like structures. These findings suggest that the lymphoepithelial relationship is important for the organization of the immunological microenvironment in tonsillar crypt epithelium of the neonatal musk shrew. PMID- 1416083 TI - Fiber differentiation of the human laryngeal muscles using the inhibition reactivation myofibrillar ATPase technique. AB - The aim of the present study was to further subdivide the type II fibers of the human thyroarytenoid and posterior cricoarytenoid muscles by means of a modified myosin ATPase reaction. In order to understand the functioning of these highly strained muscles better, it is important to know the respective percentage of fatigue-resistant type IIA fibers and fatigable type IIB fibers. The material comprised the larynges of seven laryngectomized males aged between 45 and 70 years and four laryngectomized females aged between 39 and 72 years. After having been frozen in nitrogen, 10-microns-thick sections were cut from the laryngeal muscles in a cryostat. The pH-lability of the enzyme that can be utilized in a classical myosin ATPase reaction permits a differentiation between fiber types I, IIA and IIB. Evidently, this is not possible with every human muscle. The fiber types IIA and IIB of the thyroarytenoid and the posterior cricoarytenoid muscles could be clearly distinguished by means of the inhibition reactivation myofibrillar ATPase technique. Using this method, the myosin ATPase enzyme was initially inhibited by hydroxymercuribenzoate and subsequently reactivated by cysteine. Regarding the incidence of type I and IIA fibers, there was a statistically significant difference between the thyroarytenoid and the posterior cricoarytenoid muscles. The type IIA fiber content was statistically significantly higher in the arytenoid muscle than in the posterior cricoarytenoid muscle. The percentage of type IIB fibers was low, not only in the thyroarytenoid muscle and the posterior cricoarytenoid muscle but also in the other laryngeal muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416084 TI - Ultrastructural morphometric characterization of alveolar type II cells of perinatal sheep: a comparison with adults. AB - The quantitative morphologic changes in alveolar type II cells during the perinatal period were characterized morphometrically in the lungs of fetal lambs at 132, 138, and 147 days gestational age (DGA) and in newborns at 2 days postnatal age (2 DPN). Ultrastructural features were compared with those of type II cells of ewes 365 days old. Lamellar body profile number per type II cell profile was highest at term (147 DGA) and 2 DPN. In adults, the number of lamellar body profiles and volume density of lamellar bodies were equal to those of the 132 DGA fetus. Multivesicular bodies were most common at 138 DGA and in adults. The volume density of cytoplasmic glycogen fell dramatically during the latter part of gestation. The volume density of many cellular organelles increased to the level observed in adults by term (147 DGA). Subcellular composition of type II cells of adult sheep differs from that reported for adult rats chiefly by the volume density of lamellar material within the cytoplasm. Plate-like or globe-like inclusions were present only in the type II cells of adults. Cytoplasmic extensions of the type II cell crossing the basal lamina were most abundant in the 132 and 138 DGA fetal sheep. Cytoplasmic extensions were rare in adults. We conclude that morphologic changes of the alveolar type II cell associated with gestational age follow a species-specific time course. In the sheep, this occurs during the later part of gestation and extends into the neonatal period. Morphologic and morphometric changes appear to correspond with cellular interactions between alveolar type II cells and mesenchymal cells of the interstitium. PMID- 1416086 TI - Retinal pigment epithelial fine structure in the velvet cichlid (Astronotus ocellatus). AB - The morphology of the retinal pigment epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) have been studied by light and electron microscopy in the velvet cichlid (Astronotus ocellatus). The RPE is composed of a single layer of large columnar cells. The basal (scleral) border of these cells is minimally infolded, whereas the apical (vitreal) surface displays numerous pigment-laden processes which in light-adaptation surround both rod and cone outer segments. Laterally the RPE cells are joined by a series of basally located tight junctions. Wandering phagocytes are a constant feature within this epithelial membrane. The RPE cells display a large, vesicular nucleus, numerous mitochondria, much smooth endoplasmic reticulum, polysomes, myeloid bodies, phagosomes and melanosomes. Rough endoplasmic reticulum is relatively scarce within these cells. Although only light-adapted specimens were examined, it is thought that the melanosomes are capable of extensive retinomotor movement. The endothelium of the choriocapillaris facing Bruch's membrane is typically very thin but shows few fenestrations. Bruch's membrane is typical of other teleost species in that it is composed of only three layers. PMID- 1416085 TI - Retinal photoreceptor fine structure in the velvet cichlid (Astronotus ocellatus). AB - The structure and arrangement of the retinal photoreceptors of the velvet cichlid fish (Astronotus ocellatus) have been studied by light and electron microscopy. Rods, single cones and double (twin) cones are present. In the light-adapted state, rods are very tall cells that reach deep into the retinal epithelial (RPE) layer. The long outer segment is composed of discs of uniform diameter displaying one or two incisures. The rod inner segment shows a distal ellipsoid of mitochondria, and then narrows dramatically in the myoid region. Rod nuclei are electron dense and located deep in the outer nuclear layer. Rod synaptic spherules are small and show two to three invaginated synaptic sites as well as superficial synapses. Single cones are similar to the individual members of a double cone and all display a short tapering outer segment, a large ellipsoid of mitochondria and a myoid rich in rough endoplasmic reticulum, polysomes, Golgi zones and autophagic vacuoles. Double cones have extensive subsurface cisternae along their entire contiguous surfaces. Cone nuclei are large and vesicular and located close to or through the external limiting membrane. The synaptic pedicles of cones are larger, more electron lucent, and display more invaginated (ribbon) synapses as well as conventional (superficial) synaptic sites than do the rod spherules. Rod photoreceptors certainly undergo retinomotor movements and it is probable that cones do as well. In the light-adapted state the cone photoreceptors are arranged in a repeating square mosaic pattern with one single cone surrounded by four double (twin) cones. PMID- 1416087 TI - The development of pericardial villi in the chick embryo. AB - The development of pericardial villi and their relation to the development of the cardiac surface was studied in chick embryos from the 3rd to 10th day of incubation by scanning electron microscopy. During the 3rd day of incubation (stage 14-17 HH) the coelomic epithelium covering the ventral wall of the sinus venosus forms villous protrusions. By the end of the 3rd day (stage 17 HH) these protrusions contact the dorsal wall of the heart, so that a secondary dorsal mesocardium is formed. This bridges the pericardial cavity between the ventral wall of the sinus venosus and the dorsal base of the ventricles. This sinu ventricular mesocardium exists only temporarily, as on the 8th day of incubation it becomes a part of the cardiac wall due to fusion with the epicardium of the coronary sulcus. During the 4th and 5th day of incubation (stage 17-25 HH), the formation of the epicardium proceeds from the point of attachment of the sinu ventricular mesocardium. Although these findings suggest that the epithelium of the villous protrusions spreads over the surface of the embryonic heart, one cannot exclude other hypotheses on epicardial origin. The impression of a spreading epicardium could also be created if epicardial cells were to delaminate from a local epithelium in a temporally and spatially organized pattern. PMID- 1416088 TI - Cellular distribution of the new growth factor pleiotrophin (HB-GAM) mRNA in developing and adult rat tissues. AB - Pleiotrophin (PTN), also known as HB-GAM, belongs to an emerging cytokine family unrelated to other growth factors. We report here the first comprehensive study using in situ hybridization on the cellular distribution of this new heparin binding growth factor mRNA in rat tissues. PTN mRNA was developmentally expressed in many--but not all--neuroectodermal and mesodermal lineages, whilst no PTN mRNA was detected in endoderm, ectoderm and trophoblast. PTN mRNA was found in the nervous system throughout development, with a post-natal peak of expression. In the adult nervous system, significant expression persisted in hippocampal CA1 pyramidal neurons and in cortical neurons, but also in different non-neuronal cells types in various locations (olfactory nerve, cerebellar astrocytes, pituicytes, Schwann cells surrounding the neurons in sensory ganglia). PTN mRNA was also found during development in the mesenchyme of lung, gut, kidney and reproductive tract, in bone and cartilage progenitors, in dental pulp, in myoblasts, and in several other sites. Expression was differently regulated in each location, but usually faded around birth. In the adult, PTN mRNA was still present in the meninges, the iris, the Leydig cells of the testis and in the uterus. PTN mRNA was also strongly expressed in the basal layers of the tongue epithelium, which is the only epithelium and ectodermal derivative to express PTN mRNA, and this only after birth. PTN is known to be a growth factor for perinatal brain neurons and a mitogen for fibroblasts in vitro. Recently, trophic effects on epithelial cells and a role as a tumour growth factor have been reported. The mechanisms of regulation and the functions of PTN are however still uncertain. Its expression pattern during development suggests important roles in growth and differentiation. Moreover, the presence of PTN mRNA in several adult tissues and the up-regulation of PTN mRNA expression in the gravid uterus indicate that PTN also has physiological functions during adulthood. PMID- 1416089 TI - Bone and cartilage resorption in relation to tooth development in the anterior part of the mandible in cichlid fish: a light and TEM study. AB - This paper presents ultrastructural features of the contact region between particular tooth germs and Meckel's cartilage prior to, during, and after initial resorption of the perichondral bone and of the cartilage in the cichlids Hemichromis bimaculatus and Astatotilapia burtoni. Imminent resorption opposite such teeth is announced by the presence, in this region, of a particular cell type, considered to be a stage in the cytodifferentiation of osteoclasts. Slightly later, an osteoclast with typical ruffled border is seen to open a fenestra in the perichondral bone which surrounds Meckel's cartilage. Although the action of the osteoclast is directed primarily towards the bone, it may also affect, to a much lesser extent, the underlying uncalcified cartilage. Typically, fibroblast-like cells invade the resorption cavity along with the osteoclast; the tooth germ soon follows. Capillaries are seen to invade the cartilage only at a later stage when a large cavity has been established. It is proposed that the fibroblast-like cells may have a dual function: degradation of cartilage and deposition of new bone. Although these processes are normally limited to the area surrounding tooth germs at specific loci, tooth germs in other positions may sometimes be seen invade the cartilage. They do so either passively, because of the existence of such a cavity, or as a result of their own resorption-inducing activity. Whatever the mechanism, attachment bone is being deposited within the erosion cavity and on the surface of the exposed perichondral bone. The stimuli possibly eliciting resorption of Meckel's cartilage are discussed. It is hypothesized that pressure exerted by the growing tooth germ may stimulate the osteoblasts covering the bone surface and, in this way, provoke osteoclastic bone resorption. PMID- 1416090 TI - Fine structural characteristics of the zone of contact between the lower infundibular stem and the pituitary pars distalis in the little brown bat, Myotis lucifugus. AB - The purpose of this study was to examine the morphological characteristics of the pituitary gland in the little brown bat that might influence mechanisms of hypothalamic releasing hormone transport. Paraffin sections were prepared from whole crania to examine in situ the orientations of the three parts of the adenohypophysis (pars distalis, pars intermedia, and pars tuberalis) relative to the components of the neurohypophysis (pars nervosa and infundibular stem) and the basal hypothalamus. Of particular interest was the observation that the axis of the infundibular stem is directed posteriorly from the median eminence and occupies a depression in the dorsal surface of the pars distalis as it approaches the pars nervosa. Previous studies have revealed that neuronal projections containing releasing hormones extend into the infundibular stem in this species. Therefore, we conducted a fine structural study to determine whether the zone of contact between the infundibular stem and the pars distalis could represent a site of specialized interaction between hypophysiotropic hormones and their target cells. The results show that the sparse connective tissue along this boundary contains abundant fenestrated capillaries that are exposed on one side to neurosecretory axons and on the other to cells of the pars distalis. Furthermore, secretory cells nearest these capillaries exhibit ultrastructural evidence of heightened secretory activity. We conclude that the fine structural characteristics of this zone are consistent with localized mechanisms of releasing hormone transport. PMID- 1416091 TI - Quantitative morphology of the embryonic heart: an approach to development of the atrioventricular valves. AB - In 32 human embryos ranging from 4.0 to 42 mm CR-length, the volumes of the atrioventricular endocardial cushions and of the ventricular myocardium were estimated by the point counting method. The surface densities of the left and right ventricular apical trabeculations were estimated by the point and intersection counting method. It is concluded that the cushions do not grow after the 25 mm stage, by that time having reached the maximal value of 0.074 mm3. This supports the concept that the cushions do not materially contribute to the definitive atrioventricular valves. In young embryos, the left ventricular trabeculations are thicker (as concluded from their higher surface density) than the right ventricular trabeculations. Only around the 25 mm stage, the ratio becomes 1. After this stage, right ventricles have thicker trabeculations than left ventricles have. This supports the concept that the trabecular pattern is changed during the period of valve formation, which process is characterized by delamination of the inner myocardial layers. PMID- 1416092 TI - Development of the vestibular and auditory system of the northern native cat, Dasyurus hallucatus. AB - The developing vestibular and auditory system of the native cat Dasyurus hallucatus was examined from birth to day 55 postpartum to determine when the six sensory regions had an adult structure. The utricle, a sensory epithelium with an overlying discrete population of otoliths, was present in the newborn native cat. The saccule, which has a similar structure to the utricle, and the three crista ampullaris of the semicircular canals, were present by day 21 postpartum. The organ of Corti was formed by day 50 and the external ear duct was patent by day 55 postpartum. Hair is first seen on the native cat by day 45 when the young first leave the pouch. They are left in the nest and travel on the back of the lactating mother until about day 80. The eyes open on approximately day 75. Thus, the native cat has fully functional visual, auditory, and vestibular systems when the juvenile leaves the nest. PMID- 1416093 TI - Anatomy and developmental chronology of the rat inferior alveolar nerve. AB - This report describes the anatomy of the inferior alveolar neurovascular bundle in the adult rat and provides a quantitative analysis of the developing inferior alveolar nerve (IAN). Soon after its entrance in the mandibular canal, the IAN splits into a mental nerve (MN) and an inferior dental nerve (IDN), which course in separate bony compartments. The MN passes unbranched through the mandibular canal. The IDN sends branches to the incisor, the first molar, and the second molar. The third molar (M3) is supplied by a separate IAN branch. The adult rat IAN contains 8,000-10,000 axons, 70% of which are myelinated. The MN accounts for 70% of all IAN axons, the IDN 26%, and 4% form the M3 branch. The proportion of large myelinated axons is lower in the MN than in the IDN. Following chemical sympathectomy, the IAN axon number does not change in a statistically significant way. The total number of IAN axons, which is high prenatally and neonatally, has decreased to the adult level about 1 week after birth. De novo myelination commences at birth and is complete 3-4 weeks later. The size spectrum of the myelinated fibres is narrow and unimodal during the first postnatal weeks. By 1 month, the largest fibres reach diameters of approximately 6 microns, and a bimodal pattern is emerging. From 3 months and on, the size range reaches up to 10-12 microns, and the distribution is bimodal. These data provide a basis for further studies on developmental tooth-nerve interactions. PMID- 1416094 TI - Nuclear membrane modifications in polytene nuclei of Drosophila melanogaster: serial reconstruction and cytochemistry. AB - The nuclear envelope of polytene nuclei of salivary glands of Drosophila melanogaster displays modifications consisting of nuclear envelope invaginations (NEI) and evaginations (NEE). Ultrastructural analyses combined with three dimensional reconstruction and cytochemistry show that NEI are bounded by a single membrane and that they may arise as invaginations of the inner nuclear membrane. NEI extend deeply into the nucleus. The lumens of NEI may collapse resulting in membranous sheets which may combine with those arising from adjacent NEI to form intranuclear structures resembling annulate lamellae. All NEI are associated with NEE. In contrast to NEI, NEE are enclosed in a double membrane morphologically identical to the nuclear envelope. While NEI and NEE share wheat germ agglutinin binding properties with the nuclear envelope, they differ in their ability to localize lanthanum. Pore annuli of NEI display complete lack of lanthanum binding, while those of NEE exhibit minor deposition of this cation. In contrast, pore annuli of the nuclear envelope are specifically and significantly decorated by lanthanum. A conceptual model based on the results obtained suggests that NEI are formed by invaginations of the inner nuclear membrane, together with accompanying modifications of pore complexes. PMID- 1416095 TI - Lymphatic vessels of the human dental pulp in different conditions. AB - The characteristics of the lymphatic vessel endothelial wall have been investigated in human normal and inflamed dental pulps. In normal pulps the endothelial wall is characterized by the presence of micropinocytotic vesicles and intraparietal channels. In the inflamed pulpal tissue, where an increase in interstitial fluid pressure occurs, the distended endothelial wall presents open junctions between endothelial cells and the openings of the intraparietal channels. Moreover the micropinocytotic vesicles disappear. The cytoplasm of the endothelial cells is characterized by the presence of numerous Weibel-Palade bodies, which increase in number in the dilated vessels. In the fibrillar apparatus surrounding the lymphatic vessel wall collagen fibrils are the prevalent component, while elastic fibers are not present. The different morphological properties of the lymphatic vessels are compared and discussed with regard to the variation of the functional conditions of the tissue. PMID- 1416096 TI - Capillaries measured in canine diaphragm by two methods. AB - We have measured capillary distribution in costal and crural canine diaphragm using two methods: histochemical processing and perfusion fixation. Each of 18 dogs was deeply anesthetized, the abdomen opened, and the left inferior phrenic artery cannulated. The animal was heparinized and overdosed with pentobarbital. The right hemidiaphragm was frozen, either postexcision (Protocol 1) or intact with no preload (Protocol 2), for histochemical processing. The left hemidiaphragm was fixed by perfusion in situ using 2% glutaraldehyde, either with preload (Protocol 1) or without (Protocol 2). Costal and crural regions of each hemidiaphragm were sampled for analysis. Frozen samples were sectioned and processed for acid-stable (pH 4.0) ATPase activity; perfusion-fixed samples were postfixed, stained, embedded in Epon, and sectioned. Measurements were made using a digital imaging system. We found that muscle fibers had smaller cross-sectional areas in costal than in crural diaphragm; capillary-to-fiber ratio (C:F) did not differ by region and regional differences in capillary density could be attributed to differences in fiber size. Results depended critically on methodology. In perfusion-fixed muscle, fiber area was less, C:F was greater, and capillary density was greater than in histochemically-processed tissue. We conclude that capillary distribution is similar in costal vs. crural diaphragm and that perfusion fixation identifies capillaries more effectively than histochemistry. PMID- 1416097 TI - Immobilization-induced muscle atrophy is not reversed by lengthening the muscle. AB - In clinical practice, repaired tendocalcaneus (Achilles tendon) ruptures are often protected in immobilization casts for 4 weeks in the fully plantar flexed position and for up to another 4 weeks after returning the ankle to joint neutral. Moderate to severe muscle atrophy occurs within 4 weeks of immobilization in plantar flexion, but it is not known if this atrophy is minimized or reversed following restoration of joint neutral position. We tested the hypothesis that the extent of atrophy could be reduced by returning the ankle to joint neutral after 4 weeks of immobilization. Eighteen rabbits were anesthetized, and their right hind-limbs were casted with the knee flexed 90 degrees and the ankle fully plantar flexed. Three animals each were studied after 3, 4, 6, or 8 weeks of immobilization. After 4 weeks of immobilization, the immobilization casts of the remaining six rabbits were modified to return the ankle to joint neutral for another 2 or 4 weeks. For muscle studies, the animals were anesthetized, and the soleus (SOL), plantaris (PLN), and gastrocnemius (GST) muscles were removed and weighed; the SOL and PLN were quick frozen and processed for histochemical fiber typing and fiber cross-sectional area measurement. All three muscles showed significantly reduced muscle weight to body weight ratios after 3 weeks of immobilization. SOL was the most affected, and GST was least affected. There was no significant further atrophy through 8 weeks of immobilization. The atrophy correlated with a significant reduction of mean fiber area (MFA) for Types I, IIo, and IIc fibers in SOL and PLN. In PLN, Type IIg fiber area was not significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416098 TI - Effect of cyproterone acetate on structure and function of rhesus monkey reproductive organs. AB - A low dose of Cyproterone acetate (CPA; 1 mg/kg body weight/day for 70 days) was administered to adult male rhesus monkeys to assess its effects on testicular and epididymal structure and function in a nonhuman primate species. CPA caused extensive degenerative changes in morphology of seminiferous, efferent duct, and epididymal epithelia, including decrease in diameter of seminiferous and epididymal tubules and their lumen, height of epididymal epithelium, and an increase in intertubular connective tissue. The protein profile of spermatozoa showed alterations during their epididymal transit in control and CPA-treated monkeys. In CPA-treated animals, 19 polypeptides were acquired and nine were eliminated during epididymal transit in contrast to acquisition of 12 and loss of 14 polypeptides in control animals. Treatment with CPA also resulted in the appearance of 14 new polypeptides in epididymal cytosol and luminal fluid, probably of lysosomal origin. The protein pattern of caput and cauda epididymal tubule cytosol, maintained in organ culture and exposed to 100 microM CPA for 3 days, showed absence of eight polypeptides. These results indicate that even at the low dose used in this study, CPA has caused spermatogenic arrest, degenerative changes in the epididymal structure, and alterations in epididymal and sperm protein profile. Suppression of serum testosterone levels indicates the need for androgen supplementation if CPA is to be used for male contraception. PMID- 1416099 TI - Reproduction in a South American mouse, Abrothrix longipilis. AB - Approximately 700 Abrothrix longipilis were trapped in Argentina, and their reproductive organs were studied. Some were kept briefly in captivity. Males have the same body length as females but are 8% heavier. Sexually immature males are shorter and lighter than breeding males of the same age. Few individuals in the wild live as long as two years. All overwintering males come into breeding condition in the spring and become infertile in the autumn. All overwintering females have open vaginas in the spring, and most undergo several infertile ovulatory cycles, probably without copulating, before they become pregnant. Corpora lutea of the sterile cycles accumulate; there may be as many as 28 in a pair of ovaries. The average number of ova shed per cycle is 4.66; average litter size is 3.85. Ovulation is spontaneous. There is postpartum ovulation and fertilization without intervening sterile cycles but with maintenance of old corpora lutea. Unusual architecture of the penis and vagina may result from unusual timing of hormone production during development, and the disjunction of ovulation and fertilization may similarly result from hormonal heterochrony at the beginning of the breeding season. The apparently nonadaptive wastage of ova in sterile cycles may be a novel example of kin selection. PMID- 1416100 TI - Macrostructure differences of polar fox and dog lungs. AB - The lungs of the polar fox and dog have the typical form and lobular structure characteristic of beasts of prey. Both display secondary fusion of the cranial and middle lobes in the left lung, but this is more extensive in the fox. A consistent relationship between the beast body mass and the mass and volume of the lungs is present. The relative weight of dog lungs independent of body size (weight index) is 1.7 times that of the polar fox. In the latter the parenchyma is much more subdivided than in the dog. There are 23 segments per lung pair in the polar fox, compared to 19 in the dog. Although these are of unequal size throughout the lungs of both species, corresponding segments in the fox are about half as large as those in the dog. The greater segmentation of polar fox lungs may be of assistance in restricting the spread of inflammatory processes. PMID- 1416102 TI - Fibroblast-mediated collagen gel contraction does not require fibronectin-alpha 5 beta 1 integrin interaction. AB - Fibroblasts cultured within free-floating collagen gels can bind to and reorganize the surrounding collagen fibrils into a more dense and compact arrangement. Collagen gel contraction provides an in vitro model for studying fibroblast-collagen interactions important in wound healing, fibrosis, scar contraction, and connective tissue morphogenesis. We have assessed the role of fibronectin and its interaction with the alpha 5 beta 1 "high affinity" fibronectin-specific integrin receptor in collagen gel contraction. A variety of agents, which specifically inhibit fibronectin-alpha 5 beta 1 interactions, were tested for their abilities to inhibit fibroblast-mediated collagen gel contraction. These included anti-alpha 5 beta 1 monoclonal antibodies, the synthetic peptide GRGDSP, the cell adhesive fragment of fibronectin, and an antibody against the cell adhesive region of fibronectin. None of these agents inhibited collagen gel contraction. Therefore, it is concluded that fibronectin alpha 5 beta 1 interactions are not necessary for collagen gel contraction. However, collagen gel contraction is dependent on a member or members of the beta 1 subfamily of integrin matrix receptors. A polyclonal antiserum and a monoclonal antibody, both directed against the beta 1 subunit of integrin matrix receptors, inhibited the spreading of fibroblasts in the collagen gel and inhibited collagen gel contraction. This study demonstrates that fibroblast-mediated collagen gel contraction is independent of fibronectin-alpha 5 beta 1 interactions but dependent on an interaction of beta 1 integrin matrix receptors with collagen fibers. PMID- 1416101 TI - Morphogenetic and functional activity of type II cells in early fetal rhesus monkey lungs. A comparison between primates and rodents. AB - To evaluate further the role of type II alveolar epithelial cells in primate lung development, lungs of fetal (46 to 155 days gestational age [DGA]), postnatal, and adult rhesus monkeys were investigated with antibodies against surfactant protein A (SP-A), Alcian blue (AB) staining, and periodic acid-Schiff (PAS) staining with/without alpha-amylase pre-treatment. In adult and postnatal lungs, type II cells (cuboid shape; large, roundish nucleus) displayed a unique cytoplasmic staining for SP-A. In prenatal lungs, a low-columnar to cuboid type of cell with a large, roundish nucleus was first detectable by 62 DGA. It was the only cell type to line the distalmost tubules or buds of the prospective respiratory tract. It exhibited (initially partial) cytoplasmic staining for SP A. AB and PAS stainings showed the presence of acid glycoconjugates and large apical and/or basal glycogen fields. After 95 DGA, the lining of the distal respiratory tract additionally displayed flatter cells with immunoreactivity for SP-A and non-reactive zones. Columnar epithelium (pseudostratified or simple) never stained for SP-A. We conclude that morphologically identifiable type II cells first appear in fetal rhesus monkey lungs by 62 DGA (pseudoglandular period). The cells may already synthesize surfactant and extracellular matrix components. They generate type I cells, and thus the entire pulmonary acinus lining. These conclusions for the rhesus monkey fully agree with our earlier conclusions for another primate, the human, and for rodents. However, as presently shown, primates differ greatly from rodents with respect to the timing of type II cell differentiation (at 29-38% versus 73-75% of gestation or at 22 25% versus 48-49% of prenatal lung development). PMID- 1416103 TI - Blood cells of the gilthead seabream (Sparus aurata L.): light and electron microscopic studies. AB - The peripheral blood cells of the gilthead seabream (Sparus aurata L.) were studied by light and transmission and scanning electron microscopic methods. Acidophilic erythroblasts and mature erythrocytes, round, oval, and fusiform thrombocytes, neutrophils, acidophils and basophils, lymphocytes, plasma cells, and monocyte-macrophages were characterized. A comparison of our light and electron microscopic results was carried out. The results were discussed with those for other fish species and the main modifications from the common vertebrate haematological pattern observed being considered. PMID- 1416104 TI - Effects of daily administration of prostaglandin E2 and its withdrawal on the lumbar vertebral bodies in male rats. AB - The effects of daily prostaglandin E2 (PGE2) treatment (on) and PGE2 treatment followed by withdrawal (on-off) on cancellous bone in lumbar vertebral bodies were studied in 7-month-old male Sprague-Dawley rats. The first groups of rats were given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE2/kg/d for 60, 120, and 180 days, and the second group of rats were given PGE2 for 60 days followed by withdrawal for 60 and 120 days. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified sections of fourth lumbar vertebral bodies. Systemic PGE2 treatment elevated cancellous bone mass of lumbar vertebral bodies 26-60% above control levels within 60 days and continued treatment maintained it for another 120 days, but the excess bone was lost after the treatment was withdrawn. PGE2 treatment for 60 days increased trabecular bone area, trabecular width, and bone formation parameters, and shortened remodeling periods in a dose-response manner. These changes were sustained at the levels achieved by 60-day treatment in the rats treated for 120 and 180 days. The eroded perimeter increased at day 60 and further at day 120 and then plateaued. In the on-off treated rats, the cancellous bone area, bone formation, and resorption parameters returned to near age-related controls by 60 days after withdrawal and were maintained there after 120 days of withdrawal. Therefore we conclude that the continuous treatment is needed in order to maintain the PGE2-induced bone gain. When these findings were compared to those previously reported for the proximal tibial metaphyses, we found that the proximal tibial spongiosa was much more responsive to PGE2 treatment than the fourth lumbar vertebral body. PMID- 1416105 TI - Differences in fiber number and fiber type proportion within fascicles. A quantitative morphological study of whole vastus lateralis muscle from childhood to old age. AB - Data are presented on the number of fibers and the proportion of different fiber types within fascicles of whole vastus lateralis muscles from 5 male children, 5 to 15 years of age, and compared with results from 25 male adults, middle aged and old individuals. The results verify a difference in the proportion of fibers with different properties within a fascicle. The proportion of type 2 (fast twitch) fibers on the border of fascicles is larger than the proportion internally: the children have (P less than 0.01) greater difference than the adults and the middle aged, whereas the old have (P less than 0.001) less difference than the other age groups. The mean number of fibers per fascicle increases (P less than 0.05) from childhood to adult age, and thereafter reduces (P less than 0.01). The results imply that fascicles continuously rearrange during the normal growth and development and the normal aging process. It is argued that the causes of the difference in fiber type proportions within fascicles are local factors in the muscle, secondary to the overall age related functional demands put on the fiber population. PMID- 1416106 TI - Morphology of the bile ducts of the brook lamprey, Lampetra lamottenii (Le Sueur) before and during infection with the nematode, Truttaedacnitis stelmioides (Vessichelli, 1910) (Nematoda: Cucullanidae). AB - Routine light microscopy and transmission and scanning electron microscopy were used to describe and compare the biliary tree of larval Lampetra lamottenii before and during infestation of the bile ducts with the nematode, Truttaedacnitis stelmioides. The most prominent changes to the biliary tree following infection by the parasite are the dilation of the bile ducts, alterations to their epithelial cells, and an increase in periductal fibrous tissue. In recently infected animals, the simple epithelium of dilated bile ducts often contains many mitotic figures. In long-term infestations, the epithelium is stratified or pseudostratified. Changes to the fine structure of the biliary epithelial cells include increase and/or dilation of the RER and SER, and increases in microfilaments, intermediate filaments, and microtubules. The abundance of dense bodies may reflect enhance reabsorption of biliary constituents, and their accumulation may ultimately result in cytolysis. There are increased mucous granules in the apical cytoplasm of biliary epithelial cells and an abundance of mucinous material within the bile duct lumen, and the basal lamina appears thickened. The changes to the liver of L. lamottenii following infection are discussed and compared to those reported in small mammals following bile duct ligation, in patients with extrahepatic biliary obstruction, and in parasitic infection of the biliary tree. PMID- 1416107 TI - Immunocytochemical localization of rat intestinal 15 kDa protein, a member of cytoplasmic fatty acid-binding proteins. AB - Rat intestinal 15 kDa protein (I-15P) is a member of the family of cytoplasmic fatty acid-binding proteins. Using a specific antiserum against I-15P, we studied the tissue distribution and subcellular localization of this protein in the entire rat body. By immunoblot analysis of cytosolic proteins, I-15P was detected not only in the distal portion of small intestine but also in the ovary and adrenal gland. Immunohistochemically, I-15P was localized to the absorptive epithelial cells as well as a subpopulation of enterochromaffin cells in the intestine, the lutein cells in the ovary, and subpopulations of cortical cells in the adrenal gland. Furthermore, I-15P-like immunoreactivity was also demonstrated in the surface mucous cells of stomach and the granular convoluted tubule cells of submandibular gland. Immuno-electron microscopy showed that the immunoreactivity was confined to the cytoplasmic matrix region, except in the enterochromaffin cells and granular convoluted tubule cells, where it was localized in the secretory granules. The present findings suggest that I-15P plays a role in the cellular metabolism of steroids. PMID- 1416108 TI - In vivo monastral blue-induced lamellar-bodies in lysosomes of pulmonary intravascular macrophages (PIMs) of bovine lung: implications of the surface coat. AB - We previously reported that the pulmonary intravascular macrophages (PIMs) of sheep, goat, and calf lung contained a heparin and a lipolytic lipase sensitive surface coat by using tannic acid as a component of paraformaldehyde glutaraldehyde-based fixative. The implication of this sensitivity was that the surface coat was predominantly comprised of lipoprotein-like substance. In this study we report that monastral blue (MB) used as a vascular tracer interacted with the coat globules and lost its original particulate appearance. Its precise localization in the PIMs was in combination with altered macromolecules of the surface coat in the form of lipid droplets, which conformed to the conventional view of neutral lipids. In contrast, pigment particles examined in their native state resembled metallic particles as electron-dense elliptical rods. The lipid droplets were subsequently internalized through endocytic route and found their access into the lysosomal compartments of PIMs at the electron microscopic level. Lamellar bodies (LLBs) arose from the lysosomal matrix after the entry of lipid droplets in the secondary lysosomes. Acid phosphatase activity was located in secondary lysosomes as well as in endosomes. These observations suggest that coat granules of the PIMs acted as a carrier of exogenous MB particles to deliver the complex to the lysosomal compartment where partial digestion lead to the formation of lamellar bodies. The implications of MB (cationic dye) as a vascular tracer for studying phagocytic index of PIMs in the light of their coat and the rapid development of LLBs are discussed. It is proposed that MB by initially combining with the surface coat provokes mobilization of intracellular lipid pools. In this way metabolism of vasoactive lipid in the PIMs is stimulated to influence the dynamics of pulmonary circulation in the calves. PMID- 1416109 TI - Anatomical study of the bronchial system and major blood vessels of the chicken lung (Gallus gallus) by means of a three-dimensional scale model. AB - The bronchial and vascular patterns of the chicken lung, from specimens age 8-10 days, have been studied by serial, paraffin sections of the whole organ. According to the histological structure, the bronchial system consists of three airway types: primary bronchus or mesobronchus, secondary bronchi, and tertiary bronchi or parabronchi. The mesobronchus gives rise to three sets of secondary bronchi: four dorsomedial, four dorsal, and three lateral ones. The total number of secondary bronchi is 11, which is less than the number reported in adult birds by other authors until now. Nevertheless, the number and distribution of the major vessels, arteries and veins are in basic agreement with previous descriptions. PMID- 1416110 TI - SEM of capillary pericytes prepared by ultrasonic microdissection: evidence for the existence of a pericapillary syncytium. AB - Retia mirabile of the eel swimbladder were exsanguinated, perfusion-fixed and subjected to prolonged osmication. They were then microdissected by ultrasonication which delaminated the capillary bed along planes which revealed the surfaces of arterial and venous capillaries. This procedure resulted in cleaned capillary surfaces largely free of connective tissue elements and basement membrane material. The arterial capillary segments were heavily invested with pericytes characterized by plump cell bodies containing nuclei and an extensive system of processes encircling the capillary wall. These processes exhibited a hierarchical organization consisting of primary, secondary, and tertiary elements arising roughly at right angles to each other. Primary and secondary processes exhibited frequent anastomoses and resulted in cytoplasmic continuity between adjacent cell bodies. Processes were also observed to form connections between pericytes on adjacent capillaries. These observations are evidence for the existence of a pericapillary syncytium in which cell bodies may be connected in series and in parallel throughout the arterial capillary bed. This syncytial organization would provide for a coordinated and global contractile response of pericytes to vasoactive hormones and other effectors. It may also provide for synchrony of nuclear division during developmental spread of pericytes along capillary surfaces. PMID- 1416111 TI - Structure and dynamics of adrenal mitochondria following stimulation with corticotropin releasing hormone. AB - The mitochondria of rat adrenals were investigated qualitatively and quantitatively in different functional states of the adrenal cortex. Following stimulation of the animals with corticotropin releasing hormone (CRH), the corticosterone serum levels reached a maximum 1 hour after stimulation with CRH. The amount of inner mitochondrial membrane within the zona fasciculata increased showing a biphasic time course, with a first maximum 2 hours and a second maximum 8 hours after stimulation. In contrast, a significant rise of mitochondrial volume occurred only 24 hours after CRH stimulation. Therefore, the dense vesicularization of mitochondrial cristae may constitute an early process to enhance the steroidogenic capacity of these cells. Within cells of the transition zone between zona glomerulosa and zona fasciculata, we could depict a special type of mitochondria with characteristic crescent-like cristae only seen after stimulation with CRH. This type of mitochondria may represent an intermediate form between mitochondria of zona glomerulosa and zona fasciculata underlining the impressive transformational capacity of adrenocortical mitochondria. After hypophysectomy, zona fasciculata cells contained mitochondria with tubular inner membranes, representing a hypofunctional state. In contrast, the hypofunctional state after hypophysectomy and the hyperfunctional state after stimulation of the adrenal cortex via CRH injection did not appear to correlate with the morphology of mitochondria from the zona reticularis and adrenal medulla. PMID- 1416112 TI - Transplantation of fetal mouse colon under the kidney capsule of an adult mouse: a model for the study of colonic development. AB - Fourteen-day fetal mouse colon was transplanted under the kidney capsule of an adult mouse to determine whether this system could be used as a model of embryonic colonic development. The 14-day fetal colon was transplanted and left for a period of 7 days. Comparisons of the normal one day postnatal colon and the transplanted colon were made morphologically and morphometrically. It was found that the transplanted fetal colon resembled its postnatal counterpart with respect to morphology; the cell types seen in the transplanted colon were similar to those observed in the in situ colon of the same age. However, morphometric analysis showed that the transplanted colon was significantly smaller than its postnatal counterpart, suggesting that conditions in the host were not optimal to support the full growth of the colon. In spite of this, it appears that the fetal colon can differentiate normally under the kidney capsule and this model can be used to study both epithelial-mesenchymal interactions and the role of hormones in fetal colonic development. PMID- 1416113 TI - Coronary artery development in the chick: origin and deployment of smooth muscle cells, and the effects of neural crest ablation. AB - Previous studies of coronary artery ontogeny have stressed early development and therefore have dwelt mainly upon the origin of the endothelium of the nascent coronary artery stem. This study has analyzed the ontogeny of the vascular smooth muscle cells (VSMC) in the coronary arteries of the domestic chicken, by establishing the timing and deployment of smooth muscle alpha-actin (SMAA). Anti SMAA was applied to sections of normal embryos, and to sections of experimental embryos that had undergone surgical ablation of the neural crest over somites 1 3. The results show an orderly symmetrical deployment of SMAA in control coronary arteries. SMAA was expressed significantly earlier in the coronary artery VSMC compared with those of the cardiac outflow vessels; this early expression may indicate a unique responsiveness to induction of the smooth muscle phenotype. The normal orderly development of coronary artery VSMC was dependent upon the presence of the neural crest, and therefore was disrupted in the experimental embryos whose neural crest was ablated. PMID- 1416114 TI - Anemia, hemodilution, and oxygen delivery. PMID- 1416115 TI - Effect of preoperative normovolemic hemodilution on left ventricular segmental wall motion during abdominal aortic surgery. AB - Preoperative normovolemic hemodilution (PNH) has been proposed for patients scheduled to undergo aortic surgery. Coronary artery disease is frequent in these patients. The aim of the study was to assess the effect of PNH on hemodynamics and segmental wall motion (SWM) evaluated by transesophageal echocardiography in such patients. Twenty patients with coronary artery disease were allocated randomly to either PNH or no PNH; PNH was performed after anesthetic induction using dextran 60,000. Patients were operated on under general anesthesia and monitored intraoperatively with electrocardiographic lead CM5, radial and pulmonary artery catheters, and transesophageal echocardiography positioned to obtain a short-axis view. Hemodynamic and transesophageal echocardiographic data were collected after anesthetic induction and after PNH, before and 5 min after aortic clamping, after unclamping, and at the end of surgery. Aortic clamping induced a significant increase in systemic vascular resistance and arteriovenous difference in oxygen and a decrease in cardiac index (P < 0.05), but the effect of aortic clamping was inversely related to hemodilution. The SWM score (graded from 1 = normal to 5 = dyskinesia) was significantly increased after aortic clamping, mainly in the anterior segment (P < 0.05). Four patients in the control (no PNH) group and one in the PNH group developed new SWM abnormalities indicative of myocardial ischemia during surgery (P = NS). This study suggests that PNH may improve hemodynamic tolerance to aortic clamping in patients with coronary artery disease. The observed changes in SWM indicate that PNH may not worsen myocardial ischemia in patients scheduled to undergo aortic surgery. PMID- 1416116 TI - Splanchnic hemodynamics and oxygen supply during acute normovolemic hemodilution alone and with isoflurane-induced hypotension in the anesthetized pig. AB - Safety of combined hemodilution and isoflurane-induced hypotension was assessed by studying their effects on splanchnic hemodynamics and oxygenation in nine anesthetized (ketamine/flunitrazepam) pigs. Acute normovolemic hemodilution (decrease in hematocrit from 29% to 15%) with 6% hydroxyethyl starch decreased (P < 0.05) O2 delivery despite increases in cardiac output and all splanchnic flows, as measured by electromagnetic flow probes. Superimposed isoflurane (1.45% end tidal concentrations) caused marked decreases in arterial blood pressure, cardiac output, and splanchnic flows. Oxygen uptake of the liver became O2 supply dependent. A liver surface PO2 histogram (Clark-type electrode) showed 38% of PO2 values between 0 and 5 mm Hg. Hepatic lactate uptake decreased by 75%. These data suggest that depression of cardiovascular function during reduced O2-carrying capacity adversely affects hepatic perfusion, oxygenation, and function. Combined hemodilution and isoflurane-induced hypotension may not be appropriate in patients. PMID- 1416117 TI - Greater neuromuscular blocking potency of atracurium during hypothermic than during normothermic cardiopulmonary bypass. AB - Previous studies drew attention to the greater neuromuscular blocking potency of atracurium during, than before or after, hypothermic cardiopulmonary bypass (CPB) while disregarding the periods of normothermic perfusion. We recorded the evoked twitch tension in 15 patients during nitrous oxide/narcotic anesthesia who were undergoing open heart surgery. Atracurium was injected as an initial bolus dose of 460 micrograms/kg. Waning neuromuscular blockade was enhanced by repeat injections of 138 micrograms/kg whenever the twitch tension attained 25% of control. During hypothermic (< 32 degrees C) and normothermic (> 34 degrees C) CPB, the times of onset of the maintenance doses were 57% and 18% longer, respectively, than before CPB (P < 0.05). Maintenance doses of atracurium were required every 24 +/- 4 min (mean +/- SD) before CPB, every 45 +/- 8 min (P < 0.05) during hypothermia, every 22 +/- 3 min during normothermic perfusion, and every 23 +/- 3 min after CPB. In conclusion, the patients' changing demand of atracurium paralleled the changes of temperature rather than the institution and cessation of CPB. PMID- 1416118 TI - Effects of surgical stress and volatile anesthetics on left ventricular global and regional function in patients with coronary artery disease. Evaluation by computer-assisted two-dimensional quantitative transesophageal echocardiography. AB - We investigated the effects of halothane, enflurane, and isoflurane on central hemodynamics and left ventricular global and regional function when used to control intraoperative hypertension in 39 patients with coronary artery disease. Left ventricular short-axis, midpapillary images were obtained by transesophageal echocardiography. Using a centerline algorithm, we analyzed left ventricular images for global area ejection fraction (GAEF) and segmental area ejection fraction (SAEF). The SAEF/GAEF ratio was calculated for each of eight segments. Measurements were performed after induction of anesthesia but before skin incision; 1 min after sternotomy; and during administration of the inhaled anesthetic. The increase in arterial blood pressure during sternotomy was due to an increase in vascular resistance accompanied by increases in heart rate and filling pressures while GAEF decreased. No changes in the SAEF/GAEF ratio appeared during sternotomy. The inhaled anesthetics restored arterial blood pressure by a similar decrease in vascular resistance. Isoflurane caused an increase in cardiac index that was not seen with halothane or enflurane (halothane vs isoflurane, P < 0.05). The GAEF was decreased by halothane but unaffected by isoflurane and enflurane (halothane vs enflurane; P < 0.05). Isoflurane induced a decrease in the SAEF/GAEF ratios of two segments corresponding to the inferolateral wall of the left ventricle that was, in one of these segments, significantly more pronounced compared with both halothane and enflurane. Halothane or enflurane did not cause any change in regional wall motion. We conclude that isoflurane is more likely to cause regional wall motion changes than halothane or enflurane in patients with coronary artery disease. PMID- 1416119 TI - Effects of halothane and quinidine on intracardiac conduction and QTc interval in pentobarbital-anesthetized dogs. AB - To confirm in vitro data that halothane and quinidine depressed cardiac conduction and prolonged action potential (AP) duration, the electrocardiogram and His bundle electrogram were recorded in dogs during basal pentobarbital anesthesia, after 1% halothane or quinidine (2.38 +/- 0.22 micrograms/mL serum concentration [mean +/- SEM]), or both. Purkinje fibers from a second dog were superfused with blood from the intact (support) dog, and APs were recorded. In the intact dogs, 1% halothane caused no changes in the electrocardiogram or His bundle electrogram. Quinidine prolonged QRS duration, QT interval, and rate corrected QT (P < 0.05). Ventricular conduction (HS interval) slowed, and atrial effective refractory period increased (P < 0.05). Quinidine combined with halothane widened QRS, QT, and rate-corrected QT, prolonged the HS interval, and increased the vulnerability of the atrioventricular node to conduction block. Three of 20 dogs developed torsades de pointes-type ventricular tachycardia during simultaneous quinidine and halothane administration. In cross-superfused Purkinje fibers, the AP duration to 50% repolarization was shortened, and conduction time was prolonged by 1% halothane (both P < 0.05). Quinidine decreased AP amplitude, prolonged AP duration to 90% repolarization, and slowed conduction (P < 0.05). Quinidine combined with halothane decreased AP amplitude, and prolonged both AP duration to 90% repolarization and conduction (P < 0.05). When 1% halothane and therapeutic concentrations of quinidine are administered in dogs, depressed conduction and an acquired long QT syndrome with malignant ventricular arrhythmias may develop. PMID- 1416120 TI - Differences in pH management and pulsatile/nonpulsatile perfusion during cardiopulmonary bypass do not influence renal function. AB - The renal effects of pulsatile (pulse pressure 18.0 +/- 1.5 mm Hg [mean +/- SEM]) or nonpulsatile perfusion (mean pulse pressure 1.9 +/- 0.4 mm Hg) during either alpha-stat (mean PaCO2 41.2 +/- 0.9 mm Hg measured at 37 degrees C) or pH-stat (mean PaCO2 60.6 +/- 1.7 mm Hg measured at 37 degrees C) pH management of hypothermic cardiopulmonary bypass (CPB) were studied in 100 patients undergoing elective coronary artery bypass surgery. Mean urine output, fractional excretion of sodium and potassium, and renal failure index all increased during the study period; however, there was no difference among the four different CPB management groups. Mean postoperative creatinine and blood urea nitrogen values decreased compared with preoperative values, again without differences among treatment groups. Three patients developed acute renal insufficiency; of these, two had received nonpulsatile perfusion and pH-stat management, and the other had been managed with pulsatile perfusion and pH-stat management. These three patients all had undergone prolonged CPB and required at least two vasoactive drugs and the use of an intraaortic balloon pump to be weaned from CPB. In patients with normal preoperative renal function undergoing hypothermic CPB, neither the mode of perfusion, pulsatile or nonpulsatile, nor the method of pH management, pH-stat or alpha-stat, influences perioperative renal function. PMID- 1416121 TI - Effects of sodium L-lactate and sodium racemic lactate on intraoperative acid base status. AB - Lactated Ringer's solution is frequently used to avoid metabolic acidosis during fluid resuscitation. The standard lactated Ringer's solution contains racemic lactate, an equal mixture of the D- and L-stereoisomers. We investigated whether sodium L-lactate or sodium racemic lactate (DL-lactate) is more effective for increasing buffering capacity in body fluids. For the purpose of this comparison, Ringer's solutions containing no lactate, sodium L-lactate, or racemic lactate at a concentration of 84 mEq/L (three times more than the ordinary level) were infused in patients under general anesthesia during tympanoplasty. Although differences occurred among the three groups in blood concentrations of L-lactate, D-lactate, and the L-lactate/pyruvate ratio, no differences occurred between the two lactate groups in either bicarbonate ion concentration or base excess. The amount of buffering capacity increased significantly in both lactate groups, compared with preinfusion levels, and was more than the values in the nonlactated Ringer's solution group. We conclude that sodium racemic lactate is metabolized at nearly the same rate as that of sodium L-lactate. PMID- 1416122 TI - A comparison of the effects of propofol and nitrous oxide on the electroencephalogram in epileptic patients during conscious sedation for dental procedures. AB - The influence of sedative doses of propofol or nitrous oxide on the electroencephalogram was studied in 11 mentally handicapped patients with treated epilepsy undergoing dental procedures. At one session, propofol was titrated to achieve conscious sedation. The mean (+/- SD) dose requirements were 5.5 +/- 1.1 mg.kg-1.h-1. In six patients, the electroencephalogram was unchanged during propofol administration. In three patients, there was a decrease in epileptic activity, and in two patients, paroxysmal discharges disappeared. At another session, nitrous oxide was administered by nasal mask. The mean (+/- SD) concentration of nitrous oxide needed was 43.6% +/- 4.8%. The electroencephalogram did not change in nine patients, whereas in two patients epileptic activity decreased. There were no clinical epileptoid or other adverse manifestations during any treatment or up to 48 h thereafter. The results of the present study suggest that propofol or nitrous oxide can be administered in subanesthetic doses for conscious sedation in mentally handicapped patients with treated epilepsy. PMID- 1416123 TI - Venous air embolism in prone dogs positioned with the abdomen hanging freely: percentage of gas retrieved and success rate of resuscitation. AB - Based on reports of fatal venous air embolism (VAE) occurring during lumbar laminectomy and spinal fusion in prone patients positioned with the abdomen hanging freely, it has been recommended that monitoring for VAE should be used for such cases and that a multiorificed central venous catheter should be inserted for aspiration of VAE. The present study was designed to examine aspiration of VAE when prone dogs positioned with the abdomen hanging freely were given a fatal VAE via a femoral vein. Twenty-one dogs were anesthetized with halothane and nitrous oxide in oxygen and positioned with the abdomen ventral and hanging freely, the head fixed in a stereotaxic frame, the upper extremities resting on a surface approximately 10 cm below the level of the stereotaxic frame, and the lower extremities on a surface below the level of the upper extremities (to ensure that VAE entering the inferior vena cava would ascend toward the heart). In the control group (n = 7), a central catheter was placed but was not used to aspirate VAE. In a second group (n = 7), a Cook Bunegin-Albin multiorificed catheter was inserted; and in a third group (n = 7), an American Edwards 7F Swan-Ganz catheter was inserted. Dogs were then given a predetermined lethal dose of air (5 mL/kg) over 30 s via the femoral vein. In groups 2 and 3, attempts to aspirate VAE were begun with the first decrease in expired CO2. The amounts of gas retrieved (expressed as a percent of the injected air) and the incidence of successful resuscitation were compared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416124 TI - Effect of halothane, fentanyl, and ketamine on the threshold for transpulmonary passage of venous air emboli in dogs. AB - We assumed that the capacity of the lungs to filter gas bubbles would vary as a function of anesthetic management. The effects of halothane (1% inspired concentration [group 1, n = 8]), fentanyl (100 micrograms/kg IV, followed by 1 micrograms.kg-1.min-1 [group 2, n = 7]), and ketamine (10 mg/kg IV, followed by 0.2 mg.kg-1.min-1 [group 3, n = 6]) on the passage of bolus injections of air across the pulmonary circulation were studied in dogs by using transesophageal echocardiography to detect air in the left atrium or the aorta, or both. The thresholds for bolus air detection during halothane, fentanyl, and ketamine administration were 0.05 mL/kg (range 0.01-0.1), 0.5 mL/kg (range 0.2-1.0), and 0.35 mL/kg (range 0.1-0.5), respectively. We conclude that the threshold during fentanyl- or ketamine-induced anesthesia was significantly higher than during halothane-induced anesthesia. Therefore, halothane interferes with the capacity of the lungs to filter air from the pulmonary circulation. PMID- 1416125 TI - Isoflurane and nitrous oxide: comparative impact on cerebrospinal fluid pressure in patients with brain tumors. AB - The relative effects on cerebrospinal fluid pressure (CSFP) of equipotent concentrations of isoflurane and N2O were compared in 20 patients with brain tumors who had lumbar subarachnoid catheters in place. Patients were randomly assigned to receive one of two anesthetic sequences: group 1, 0.7% end-tidal isoflurane in O2, which was changed to 70% N2O in O2; or group 2, 70% N2O in O2, which was changed to 0.7% end-tidal isoflurane in O2. End-tidal PCO2 and percent end-tidal N2O and isoflurane were monitored by mass spectrometry from just before changing anesthetics (time = 0 min) until the end of a 20-min observation period (time = 20 min). Ventilation was held constant at PaCO2 = 36 +/- 1 mm Hg (mean +/ SE). The patients in group 1 sustained an increase in CSFP that reached a maximum of 33% above the value at 0 min, despite a 3-mm Hg decrease in PaCO2 (P < 0.05). By contrast, CSFP remained unchanged in group 2. Although the absolute increase in CSFP after replacement of isoflurane/O2 by N2O/O2 anesthesia was relatively small (9 +/- 1 to 12 +/- 2 mm Hg; P < 0.05), the absence of a similar effect in patients where N2O was replaced by isoflurane suggests that replacement of isoflurane by an equipotent concentration of N2O is more likely to lead to an increase in CSFP in patients with altered intracranial dynamics than is replacement of N2O by isoflurane. PMID- 1416126 TI - Effect of partial neuromuscular blockade on intraoperative electromyography in patients undergoing resection of acoustic neuromas. AB - Intraoperative electromyographic monitoring of the facial nerve during acoustic neuroma excision provides early detection of nerve injury and improved outcome. To determine whether a useful level of peripheral neuromuscular blockade could be achieved without compromise of facial electromyographic monitoring, we studied 10 patients undergoing resection of acoustic neuroma. Facial nerve monitoring was accomplished by placement of wire electrodes in the orbicularis oris, orbicularis occuli, and mentalis muscles. Peripheral neuromuscular blockade was assessed by recording unprocessed hypothenar compound muscle action potentials (CMAPs). After induction of anesthesia, an infusion of atracurium (1.0 micrograms.kg-1.min-1) accompanied by a bolus dose of 50 micrograms/kg was administered. The infusion was then increased in increments of 0.5 micrograms.kg-1.min-1 until a 50% reduction in hypothenar single-twitch CMAP was obtained. Facial nerve function was continuously monitored by comparison of facial CMAPs produced by stimulation of the nerve proximal and distal to the tumor bed. The mean (+/- SD) infusion rate of atracurium was 2.55 +/- 0.75 micrograms.kg-1.min-1. Decrements in facial nerve CMAPs were detected in 6 of 10 patients, and all demonstrated moderate to severe facial nerve dysfunction. In no patient was an unexpected deficit present postoperatively. Moderate degrees of peripheral neuromuscular blockade can be achieved without compromising facial nerve electromyographic monitoring. PMID- 1416127 TI - Comparison among intrathecal fentanyl, meperidine, and sufentanil for labor analgesia. AB - This study compared the analgesic efficacy of intermittent injections of intrathecal fentanyl (10 micrograms), meperidine (10 mg), or sufentanil (5 micrograms) administered to 65 parturients during the first stage of labor. The groups did not differ in onset or duration of effective analgesia. The meperidine group, however, had significantly lower pain scores once cervical dilation progressed beyond 6 cm. Side effects included mild pruritus and nausea. After intrathecal drug injection, variable decelerations of the fetal heart rate increased in the fentanyl and meperidine groups. All neonates had a 5-min Apgar score of 7 or more. We conclude that intermittent intrathecal injections of fentanyl, meperidine, or sufentanil can provide adequate first-stage labor analgesia. Meperidine appears to provide more reliable analgesia as the first stage of labor progresses. PMID- 1416128 TI - Nalbuphine is better than naloxone for treatment of side effects after epidural morphine. AB - This study compared naloxone and nalbuphine when administered for treatment of side effects after epidural morphine, 5 mg, given for postcesarean analgesia. Patients requesting treatment for pruritus or nausea randomly received, in a double-blind fashion, up to three intravenous doses of either naloxone 0.2 mg (group 1; n = 20) or nalbuphine 5 mg (group 2; n = 20). The incidence of vomiting, the severity of nausea and pruritus, and the degree of sedation and pain were assessed before and 30 min after each dose. The first dose of nalbuphine decreased the incidence of vomiting (P < 0.005) and the severity of nausea and pruritus (P < 0.01), whereas naloxone caused no significant changes. Sedation scores increased after nalbuphine (P < 0.05) and remained unchanged after naloxone, whereas pain scores increased after naloxone (P < 0.01) and were unchanged after nalbuphine. Eighteen patients in group 1 and 12 in group 2 received a second dose, and 8 and 4 patients, respectively, a third dose. Other than decreased pruritus after the second dose with both drugs, no further changes occurred. We conclude that nalbuphine is superior to naloxone for the treatment of side effects after epidural morphine. However, persistent symptoms may require supplemental therapy, as repeated doses proved less effective than the initial dose. PMID- 1416129 TI - Adverse effects of epidural 0.03% bupivacaine during analgesia after cesarean section. AB - To develop a regimen that would provide good analgesia after cesarean section with minimal side effects in the setting of prolonged (> 24 h) epidural infusion, buprenorphine or fentanyl was combined with 0.03% bupivacaine in a double-blind study of 23 parturients. Patients were randomly assigned to two groups: group I (n = 12), patient-controlled analgesia by epidural infusion of buprenorphine (3 micrograms/mL) with 0.03% bupivacaine; group II (n = 11), patient-controlled analgesia by epidural infusion of fentanyl (2 micrograms/mL) with 0.03% bupivacaine. Plasma for determination of opioid concentrations was obtained at intermittent intervals. Pain relief was similar and satisfactory in both groups. The median overall satisfaction score was higher (10.0 vs 7.5; P < 0.03) for group II. Pruritus was mild in most patients. Nausea and vomiting, which were most disturbing to the patients, were seen only with buprenorphine. No patient had a respiratory rate of < 12 breaths/min. Mean plasma opioid concentrations did not exceed 1 ng/mL during the study. However, four patients (33%) in group I and six patients (55%) in group II experienced sensory loss in the lower extremities, which made ambulation difficult. One patient in each group developed extensive pressure blisters on both heels. These complications led us to terminate the study. We conclude that 0.03% bupivacaine used in combination with an opioid in prolonged epidural infusions produces a high incidence of sensory loss in the lower extremities and is unsuitable for situations in which early ambulation is desired. PMID- 1416130 TI - Preoxygenation of pregnant and nonpregnant women in the head-up versus supine position. AB - The influence of preoxygenation in the supine (n = 10) versus the 45 degrees head up (n = 10) position on the duration of apnea leading to a decrease in arterial oxygen saturation to 95%, as monitored by pulse oximetry, was investigated in 20 women undergoing elective cesarean section at term of pregnancy. The results were compared with those obtained in a control group of 20 nonpregnant women. In the supine position, the average time to desaturation to 95% was significantly shorter in the pregnant group (173 +/- 4.8 s [mean +/- SD]) than in the control group of nonpregnant women (243 +/- 7.4 s). Using the head-up position resulted in an increase in the desaturation time in the nonpregnant group (331 +/- 7.2 s) but had no significant effect in the pregnant group (156 +/- 2.8 s). We conclude that pregnant women desaturate their arterial blood of oxygen more rapidly than do nonpregnant women. Furthermore, the head-up position extends the duration of apnea that can take place before desaturation occurs in nonpregnant patients. PMID- 1416131 TI - Metoclopramide-enhanced analgesia for prostaglandin-induced termination of pregnancy. AB - We previously determined that a single dose of metoclopramide could significantly reduce the patient-controlled analgesia (PCA) morphine requirements of women undergoing prostaglandin-induced termination of pregnancy. In the present study, we evaluated whether repeated doses of metoclopramide would further reduce pain and accelerate expulsion of the fetus. After intraamnionic injection of prostaglandin, patients were randomly allocated to receive either 10 mg of intravenous metoclopramide (n = 17) or saline (n = 15), concurrent with the initiation of PCA. A second, identical dose was administered 4 h later. Data included visual analogue scale scores for pain 45 min after each administration of metoclopramide or saline and visual analogue scale and sedation scores every 2 h for the first 10 h, amount of morphine delivered by PCA pump, time of fetal and placental passage, and hospital discharge. Metoclopramide-treated patients experienced significantly earlier fetal and placental passage (P < 0.05). This was associated with a 66% reduction in PCA morphine received by the time of fetal delivery (P < 0.05). In addition, patients in the metoclopramide group were discharged from the hospital significantly sooner (P < 0.05). This difference included fewer second-day hospital stays (P < 0.05). Visual analogue scale scores measured 45 min after each infusion of the study agent were reduced from baseline in the metoclopramide group only (P < 0.05). No significant intergroup differences were noted with respect to pain or interval morphine usage. We conclude that repeated doses of metoclopramide significantly reduce the duration of induced labor and therefore the total PCA morphine requirements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416132 TI - A comparison of methods for the detection of myocardial ischemia during noncardiac surgery: automated ST-segment analysis systems, electrocardiography, and transesophageal echocardiography. AB - Clinicians often fail to detect intraoperative ischemic electrocardiographic (ECG) changes when viewing oscilloscopes. Automated ST-segment monitors promise to increase the detection of such ECG changes. We investigated the capacity of two commercially available ST-segment monitors to detect intraoperative myocardial ischemia in patients at high risk for developing intraoperative myocardial ischemia during vascular and other noncardiac procedures. The ST segment monitors were compared with two reference monitors: (a) printed eight lead ECGs, as interpreted by a cardiologist, and (b) the presence of segmental wall motion abnormalities and thickening abnormalities detected by transesophageal echocardiography (TEE). We also examined the capacity of the printed ECG to diagnose myocardial ischemia when compared with TEE. We studied 44 patients who underwent TEE, printed multilead ECG, oscilloscope monitoring of leads V5 and II, and measurement of ST-segment deviation from the baseline using an automated Hewlett Packard ST-segment device. The sensitivities for the Hewlett Packard system were 40% for TEE-diagnosed myocardial ischemia and 75% for ECG diagnosed ischemia. Comparison of the printed ECG with TEE revealed that ST segment changes in the printed ECG, as analyzed by a cardiologist, were 25% sensitive and 62% specific for the detection of TEE-diagnosed myocardial ischemia. When T-wave inversions were added to ST-segment depression as a criterion for the diagnosis of myocardial ischemia by the printed ECG, the sensitivity of ECG for the detection of intraoperative myocardial ischemia, as determined by TEE, was 40% and specificity was 58%. Twenty-three of the 44 patients were simultaneously monitored in leads I, II, and V5 with an automated Marquette ST-segment monitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416133 TI - Lung traction causes an increase in plasma prostacyclin concentration and decrease in mean arterial blood pressure. AB - The effects of lung traction on arterial blood pressure and plasma prostacyclin concentrations were studied in five patients undergoing partial pneumonectomy or lobectomy. After manual traction of a lung segment, mean arterial blood pressure decreased from 77 +/- 5 mm Hg (mean +/- SEM, before lung traction) to 59 +/- 5 mm Hg. The concentrations of 6-keto prostaglandin F1 alpha (a stable breakdown product of prostacyclin) increased significantly from 46 +/- 6 pg/mL (mean +/- SEM, before thoracotomy) to 593 +/- 91 pg/mL. Four of five patients showed facial flushing and palmar erythema. Arterial blood pressure returned to pretraction value, and both the facial flushing and palmar erythema disappeared within 30 min after lung traction. These results suggest that traction of the lung stimulates release and/or production of prostacyclin, which results in facial flushing, palmar erythema, and decrease in arterial blood pressure. PMID- 1416134 TI - Comparison of two techniques to inflate the bronchial cuff of the Univent tube. AB - The Univent tube is an endotracheal tube with a movable bronchial blocker. The blocker cuff reportedly exhibits high-pressure characteristics when inflated to seal any adult bronchus. This study was aimed at measuring the cuff volume that would seal the bronchus when two different techniques of cuff inflation were used. One technique is based on creating negative pressure and the other is based on creating positive pressure within the breathing system. In addition, we directly measured the compliance characteristics of the cuff. The study was performed in eight adult patients undergoing thoracotomy. The negative pressure technique of cuff inflation (NPT) was tested by applying -150 mm Hg of pressure to the blocker lumen, causing loss of volume in the breathing system as evidenced by deflation of the reservoir bag. The blocker cuff was then inflated until the bag ceased to deflate. In the positive pressure technique of cuff inflation (PPT), the blocker lumen was connected to a beaker of water while maintaining pressure of +30 mm Hg within the breathing system. The bronchial cuff was then inflated until air bubbles ceased to appear in the beaker. Direct measurement of compliance of the blocker cuff confirmed its high-pressure characteristics. Bronchial sealing volume ranged from 3 to 5 mL when measured with the NPT and from 4 to 6 mL when measured with the PPT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416135 TI - Tracheal intubation without the use of muscle relaxants: a technique using propofol and varying doses of alfentanil. AB - We have noted that tracheal intubation can be accomplished in many patients after induction of anesthesia with propofol and alfentanil without the simultaneous use of muscle relaxants. This study was designed to evaluate airway and intubating conditions after administration of propofol and alfentanil in 75 ASA physical status I or II outpatients with Mallampati class I airways undergoing various surgical procedures. The patients were randomly assigned to one of five groups for induction of anesthesia. All patients received midazolam 1 mg IV before induction of anesthesia. Group I patients (n = 15) received d-tubocurarine 3 mg, thiamylal 4 mg/kg, and succinylcholine 1 mg/kg IV. Groups II-V patients (n = 15 each) received alfentanil 30, 40, 50, or 60 micrograms/kg followed by propofol 2 mg/kg IV. No muscle relaxants were given to patients in groups II-V. Airway management was performed by one of the authors who was blinded as to the dose of alfentanil administered. After loss of consciousness, patients' lungs were ventilated via face mask, and the ease of ventilation was recorded. Jaw mobility was also assessed. Ninety seconds after administration of the propofol or thiamylal, laryngoscopy was performed and exposure of the glottis and position of the vocal cords were noted. Intubation of the trachea was performed and patient response was noted. Heart rate and arterial blood pressure were also recorded before induction of anesthesia, after induction, and then again after intubation of the trachea. The lungs of all patients were easily ventilated via mask, and the jaw was judged to be relaxed in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416136 TI - Comparison of the anesthetic requirement for tolerance of laryngeal mask airway and endotracheal tube. AB - We tested the hypothesis that the laryngeal mask airway (LMA) is tolerated at lighter levels of anesthesia than an endotracheal tube (ET). We studied 20 unpremedicated, nonsmoking ASA physical status I or II patients aged 18-40 yr whose surgery lasted > 1 h. Subjects were randomly assigned to receive either an ET or LMA. Anesthesia was induced with intravenous propofol and the LMA or ET was inserted. The ET-group patients received 1.5 mg/kg of succinylcholine, preceded by vecuronium (0.015 mg/kg IV). Maintenance of anesthesia was with only isoflurane and approximately 66% N2O in O2 by spontaneous ventilation. All gas concentrations were measured by a Raman spectrometer sampling from the breathing circuit end of the LMA or ET. Toward the end of the procedure, the end-tidal N2O and isoflurane concentrations were allowed to decrease to < 3 vol% and 0.8 +/- 0.05 vol%, respectively. The end-tidal isoflurane concentration was then decreased in 0.1% +/- 0.05% decrements, each stable value being held for 5 min. The patient was observed for signs of reaction to the presence of the LMA or ET. The mean (range) end-tidal isoflurane concentrations for reaction to ET and LMA were 0.55% (0.4-0.7) and 0.35% (0.2-0.51), respectively (P < 0.001). These data confirm the original hypothesis of the study. PMID- 1416137 TI - Profound hemodilution: what is the critical level of hemodilution at which oxygen delivery-dependent oxygen consumption starts in an anesthetized human? PMID- 1416138 TI - Insertion of the laryngeal mask airway in awake infants with the Robin sequence. PMID- 1416139 TI - Extracorporeal membrane oxygenation for perioperative support during congenital tracheal stenosis repair. PMID- 1416140 TI - Management of a difficult airway in a patient with Hurler-Scheie syndrome during cardiac surgery. PMID- 1416141 TI - Perioperative management of neonatal ectopia cordis: report of three cases. PMID- 1416142 TI - Intraoperative hypoxemia complicating laparoscopic cholecystectomy in a patient with sickle hemoglobinopathy. PMID- 1416143 TI - An unusual presentation of spinal cord tumor after epidural anesthesia. PMID- 1416144 TI - Transesophageal echocardiographic detection of a right atrial thrombus around a pulmonary artery catheter. PMID- 1416145 TI - Intraoperative exacerbation of Parkinson's disease. PMID- 1416146 TI - Intraoperative hypertension during surgical excision of neuroblastoma. Case report and review of 20 years' experience. PMID- 1416147 TI - Propofol in cardiac catheterization. PMID- 1416148 TI - Propofol for radiation therapy in small children. PMID- 1416149 TI - Myelopathy and back pain--take heed. PMID- 1416150 TI - Epidural hematoma: was catheter removed during complete anticoagulation? PMID- 1416151 TI - Long-distance anesthesia. PMID- 1416152 TI - An atraumatic oral and nasotracheal intubation guide probe. PMID- 1416153 TI - More on epidural fentanyl analgesia. PMID- 1416155 TI - Cannulation of vessels using a spring-loaded device. PMID- 1416154 TI - Malignant hyperthermia during sevoflurane anesthesia. PMID- 1416156 TI - Use of transesophageal echocardiogram for intracardiac thrombus related to postoperative atrial fibrillation. PMID- 1416157 TI - Substance abuse. Now, and for some time to come. PMID- 1416158 TI - ASA Award: John P. Kampine. PMID- 1416159 TI - A randomized, double-blind comparison of lumbar epidural and intravenous fentanyl infusions for postthoracotomy pain relief. Analgesic, pharmacokinetic, and respiratory effects. AB - Although epidural opioids frequently are used to provide postoperative analgesia, several articles have suggested that the analgesia after epidural fentanyl is similar to that after an equal dose of fentanyl given intravenously. To address this issue further, 29 postthoracotomy patients were studied in a randomized, double-blinded trial comparing a lumbar epidural fentanyl infusion with an intravenous fentanyl infusion for analgesia, plasma fentanyl pharmacokinetics, and respiratory effects for 20 h postoperatively. In all patients in both groups, good analgesia was achieved (pain score less than 3, maximum 10) over a similar time course, although the patients receiving epidural infusion required a significantly larger fentanyl infusion dose than did the patients receiving intravenous infusion (group receiving epidural fentanyl infusion: 1.95 +/- 0.45 micrograms.kg-1.h-1; group receiving intravenous fentanyl infusion: 1.56 +/- 0.36 micrograms.kg-1.h-1; P = 0.0002). The time course for the plasma fentanyl concentrations was similar in the two groups, and plasma fentanyl concentrations were not significantly different at any sampling period (T7-T20; group receiving epidural fentanyl infusion: 1.8 +/- 0.5 ng/ml; group receiving intravenous fentanyl infusion: 1.6 +/- 0.6 ng/ml; P = 0.06). Similarly, calculated clearance values for the two groups were not significantly different (group receiving epidural fentanyl infusion: 0.95 +/- 0.26 l.kg-1.h-1; group receiving intravenous fentanyl infusion: 0.87 +/- 0.25 l.kg-1.h-1; P = 0.3). Both groups demonstrated a similar degree of mild to moderate respiratory depression postoperatively, which was assessed with continuous respiratory inductance plethysmography and sequential arterial blood gas analysis. Side effects (nausea, vomiting, pruritus) were mild and did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416160 TI - ST segment depression during labor and delivery. AB - ECG changes suggestive of myocardial ischemia are common during cesarean delivery under regional anesthesia. To determine the time course, duration, and significance of these ECG changes, we monitored 111 parturients with continuous ambulatory ECG (Holter) during and after cesarean delivery. Twenty-two parturients undergoing vaginal delivery were similarly monitored. ST segment depression was present in 25% of patients undergoing cesarean delivery but was not found in those patients delivering vaginally. ST segment elevation was not detected in either group. The incidence of ST segment depression during cesarean delivery was similar with epidural (29%), spinal (17%), and general (18%) anesthesia, occurring most commonly in the 30 min following delivery (P less than 0.001). Transthoracic echocardiographic imaging was performed in 23 patients undergoing cesarean section. Five of the 23 patients had seven episodes of intraoperative ST segment depression. Regional wall motion abnormalities were not present in any patient. A decrease in ejection fraction area greater than 15% from baseline or from previous interval ejection fraction area was present during four episodes of ST change. Three episodes of ST depression were not associated with significant decreases in ejection fraction area. Precordial Doppler monitoring for detection of venous air embolism in 25 patients revealed no association between the occurrence of venous air embolism and ST segment depression. We conclude that although significant myocardial impairment during cesarean delivery does not occur, episodes of ST depression may not all be merely an artifact of parturition. PMID- 1416161 TI - Elderly, conscious patients have an accentuated hypotensive response to nitroglycerin. AB - There is no adequate explanation for the highly variable response of systemic blood pressure to nitroglycerin (glyceryl trinitrate [GTN]). Aging produces cardiovascular changes that should alter the effects of GTN, but elderly patients usually have been excluded from studies of GTN. Accordingly, the authors compared the effects of GTN on systemic blood pressure in elderly and younger patients. Fifty-three patients, aged 49-87 (with 30 patients older than 70), were studied. Before elective vascular surgery, 14 patients received an infusion of placebo; 26, a constant infusion of GTN; and 13, a stepwise increasing infusion of GTN. After a standardized anesthetic induction and the start of surgery, the identical infusion protocols were repeated in each group. Data on GTN infusion rate, arterial blood pressure, and GTN concentrations versus time, age, and other potentially influencing variables were pooled for analysis. Before anesthesia and surgery, GTN more commonly caused excessive hypotension in patients older than 70 yr than in younger patients, but none of the patients had complications. A repeated-measures model analysis indicated that age significantly influenced the effects of GTN on blood pressure. That is, patients who are in their 70s who receive 0.5 micrograms.kg-1.min-1 of GTN are predicted to experience a twofold greater decrease in systolic arterial pressure (approximately 33 mmHg) than patients in their 50s. However, no apparent effect of age on intraoperative GTN responsiveness was discernible nor was a predictable relationship found between the preoperative and intraoperative responsiveness or between arterial concentrations of GTN and blood pressure or age. Therefore, the authors conclude that, in the absence of the effects of anesthesia and surgery, elderly patients have a more pronounced blood pressure response to GTN than younger patients. Furthermore, the authors conclude that preoperative blood pressure responsiveness to GTN is not a reliable predictor of intraoperative responsiveness. PMID- 1416162 TI - Kinetics of cerebral deoxygenation during deep hypothermic circulatory arrest in neonates. AB - Brain injury associated with neonatal congenital heart operations performed during deep hypothermia and/or total circulatory arrest is often attributed to cerebral hypoxia. We studied the kinetic changes in cerebrovascular hemoglobin O2 saturation (HbO2%) and total hemoglobin concentration (Hbtotal) in 17 neonates undergoing cardiac surgery as they were cooled to 15 degrees C, underwent total circulatory arrest, and were rewarmed. HbO2% and Hbtotal in brain vasculature were monitored noninvasively by near-infrared spectroscopy. Neonates were cooled over 12 min and rewarmed over 15 min while being perfused using cardiopulmonary bypass (CPB). Total circulatory arrest lasted from 20 to 70 min. We found that HbO2% in brain vasculature increased during the initial 8 min of CPB as nasopharyngeal temperature decreased, and then remained constant until circulatory arrest. After the onset of circulatory arrest, cerebrovascular HbO2% decreased curvilinearly for 40 min; no further hemoglobin desaturation was observed from 40 to 70 min of arrest. The changes in cerebrovascular Hbtotal were quite different from those in HbO2%, as Hbtotal decreased during the initial minute of CPB and circulatory arrest and then remained constant until recirculation. Brain intravascular HbO2% and Hbtotal increased within 3 min after the onset of recirculation to prearrest levels, and during rewarming, HbO2% decreased to normothermic baseline values. The results demonstrate that cerebral oxygenation increased during CPB cooling; O2 was consumed by the neonatal brain during the initial 40 min of deep hypothermic circulatory arrest; and cerebral oxygenation was restored on recirculation. These observations may be important in identifying the etiologies of brain injury during neonatal congenital heart surgery. PMID- 1416163 TI - Spectral analysis of heart rate variability during isoflurane anesthesia. AB - The autonomic nervous system is an important neural control system for maintaining cardiovascular stability in humans. Analysis of heart rate variations may provide important clinical information on the influence of anesthesia on the autonomic nervous system and the central nervous system. Therefore, the effects of 1.0, 1.5, and 2.0 minimum alveolar concentrations of isoflurane anesthesia on beat-to-beat heart rate variations were studied in ten patients (ASA Physical Status 1). Spectral analysis was used to determine the intensity of the variations. For each power spectrum, the frequency components were identified as follows: 1) the parasympathetically mediated respiratory component (0.15-0.4 Hz) and 2) both parasympathetically and sympathetically mediated components (0.04 0.15 Hz). The latter was subdivided into the low-frequency component (0.04-0.09 Hz) of vasomotor origin and the mid-frequency component (0.09-0.15 Hz) of baroreceptor origin. Marked reductions in the power of heart rate variations, at all frequencies, were found during isoflurane anesthesia, indicating isoflurane decreased total autonomic nervous system activity. Isoflurane decreased the high frequency and mid-frequency components in a concentration-dependent manner. The low-frequency component increased transiently at 1.5 minimum alveolar concentrations concomitant with the burst suppression in the electroencephalogram. The ratio of mid-frequency to high-frequency components did not change significantly during isoflurane anesthesia compared with the awake period. These frequency characteristics of heart rate variations during isoflurane anesthesia suggest there are dose-related decreases in autonomic nervous system activity in both the vagus and the cardiac sympathetic nerves. PMID- 1416165 TI - Monitoring of brainstem function during vertebral basilar aneurysm surgery. The use of spontaneous ventilation. AB - Monitoring of cardiovascular, respiratory, and evoked potential parameters has been advocated during posterior fossa surgery to detect brainstem ischemia that may result from surgical manipulations. We report here our retrospective and smaller prospective experience of spontaneous ventilation as a monitor in patients undergoing vascular surgical procedures in the posterior fossa. Forty patients' charts were reviewed retrospectively, and 10 patients were studied prospectively. Respiratory changes in the retrospectively studied group occurred in 9 patients. Four patients developed apnea during temporary occlusion of the vertebral artery. These respiratory changes were associated with simultaneous cardiovascular changes in only 2 patients, and of the 13 patients monitored with evoked potentials, only 2 had simultaneous evoked potential changes. In the prospectively studied group, respiratory changes occurred in 4 patients. Three patients (2 with apnea during temporary occlusion) had a simultaneous change in evoked potentials but no cardiovascular changes. One patient had a change in all three parameters. Allowing our patients to breathe spontaneously provided an early and rapid indication of brainstem ischemia, especially during the temporary occlusion of the vertebral basilar artery system. PMID- 1416164 TI - Comparison of postoperative respiratory function after laparoscopy or open laparotomy for cholecystectomy. AB - Cholecystectomy performed via laparotomy is associated with reduction of lung volumes including functional residual capacity that may lead to postoperative hypoxia and atelectasis. Laparoscopic cholecystectomy is associated with faster recovery compared to open laparotomy and cholecystectomy. To determine whether laparoscopic cholecystectomy was associated with less pulmonary dysfunction, 20 patients (ASA Physical Status I) undergoing elective cholecystectomy were randomly assigned to surgical teams performing either laparoscopy or open laparotomy for cholecystectomy. Patients in whom one or the other surgical technique had to be performed for medical or psychologic indications were excluded from the study. A standardized anesthetic technique and postoperative analgesic regimen were used. Forced vital capacity and forced expiratory volume in 1 s; functional residual capacity determined by a closed-circuit, constant volume helium dilution technique; and arterial O2 and CO2 tensions were measured preoperatively and at 6, 24, and 72 h postcholecystectomy. Forced vital capacity and forced expiratory volume in 1 s were significantly greater (P less than 0.05) in the laparoscopy compared to the laparotomy group at 6, 24, and 72 h postoperatively. Forced vital capacity relative to preoperative values was significantly (P less than 0.05) greater in patients with laparoscopy (24 h, 70 +/- 14%; 72 h, 91 +/- 6%) compared to open laparotomy (24 h, 57 +/- 23%; 72 h, 77 +/- 14%). Similarly, forced expiratory volumes in 1 s relative to preoperative values were significantly (P less than 0.05) greater in patients with laparoscopy (24 h, 85 +/- 13%; 72 h, 92 +/- 9%) compared to open laparotomy (24 h, 54 +/- 22%; 72 h, 77 +/- 11%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416166 TI - Pancuronium increases the duration of electroencephalogram burst suppression in dogs anesthetized with isoflurane. AB - Earlier studies have demonstrated both a decrease as well as no effect on halothane MAC after administration of nondepolarizing neuromuscular relaxants. To clarify further the relationship between neuromuscular blocking agents and anesthetic potency, the authors studied the effect of pancuronium on steady-state electroencephalogram (EEG) burst suppression produced by isoflurane in dogs. Anesthesia was induced using isoflurane and oxygen via mask without the administration of other drugs. The trachea was intubated, and isoflurane was administered at a concentration sufficient to produce EEG burst suppression. Thereafter, end-tidal isoflurane concentration, temperature, and end-tidal PCO2 were meticulously maintained at constant values. Dogs in group 1 (n = 6) received pancuronium 0.1 mg.kg-1. The percent of the EEG that was isoelectric increased from 21 +/- 9% (mean +/- SD) to 35 +/- 11% (P less than 0.01). After the return of single-twitch response to train-of-four stimulation, neostigmine 0.05 mg.kg-1 and glycopyrrolate 0.01 mg.kg-1 were administered. This resulted in a reduction in EEG isoelectricity to 19 +/- 8% (P less than 0.01), similar to the value before pancuronium administration. In group 2 dogs (n = 6), the percent isoelectricity of the EEG prior to pancuronium was 25 +/- 10%. After administration of pancuronium 0.02, 0.04, and 0.2 mg.kg-1 sequentially, the percent isoelectricity of the EEG was 29 +/- 11, 37 +/- 15, and 43 +/- 9%, respectively. This represents a dose-related increase in isoelectricity for the 0.04- and 0.2-mg.kg-1 doses (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416167 TI - Positive end-expiratory pressure reduces renal excretion without hormonal activation after volume expansion in dogs. AB - Controlled mechanical ventilation (CMV) with positive end-expiratory airway pressure decreases urine output and renal sodium excretion. This study investigates--independent of surgical stress, general anesthesia, and sedation- the influences of antidiuretic hormone, atrial natriuretic peptide, plasma renin activity, and aldosterone on decreased urine output and renal sodium excretion during CMV with positive end-expiratory airway pressure. Hemodynamic, renal, and hormonal parameters were measured over a 4-h period in six trained, nonanesthetized, chronically tracheotomized dogs under two conditions: 1) control: hours 1-4, spontaneous breathing at continuous positive airway pressure of 4 cmH2O; and 2) CMV 20: hour 1, continuous positive airway pressure of 4 cmH2O; hours 2 and 3, CMV with a mean airway pressure of 20 cmH2O; and hour 4, continuous positive airway pressure of 4 cmH2O. Throughout the experiments, 0.5 ml.kg body weight-1.min-1 balanced electrolyte solution was administered intravenously. During the 2nd and 3rd h of CMV 20, urine volume decreased by 43% and sodium excretion decreased by 44% when compared with control values (P less than 0.05). The glomerular filtration rate decreased from 4.4 +/- 0.1 to 3.9 +/- 0.1 ml.kg-1.min-1 (P less than 0.05) during the 2nd h and from 4.4 +/- 0.1 to 4.1 +/- 0.1 ml.kg-1.min-1 (P less than 0.05) during the 3rd h of CMV 20. Fractional sodium excretion decreased from 4.7 +/- 0.3% to 2.9 +/- 0.2% (P less than 0.05) during the 2nd h and from 7.5 +/- 0.3% to 4.6 +/- 0.2% (P less than 0.05) during the 3rd h of CMV 20, compared with values during the control period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416168 TI - The inhibitory effect of halothane on mesenteric venoconstriction and related reflex responses during acute graded hypoxia in rabbits. AB - Systemic hypoxia is a common abnormality encountered frequently in the clinical setting that produces compensatory cardiopulmonary changes affecting heart rate, blood pressure, peripheral vascular resistance, and respiratory drive. These changes are known to be inhibited or reversed by inhaled anesthetics. More recently, chemoreflex-mediated constriction of capacitance veins has been identified as a mechanism that contributes significantly to the hemodynamic adjustments during hypoxia. However, the effects of anesthetics on this response have not been clarified. The current study was designed to quantify sympathetically mediated mesenteric venoconstriction as well as heart rate and blood pressure responses to acute graded hypoxia; to identify the inhibitory effects of inhaled halothane on these responses; and to estimate the contribution of the peripheral chemoreceptors in mediating these changes. Changes in mesenteric vein diameter were measured in alpha-chloralose anesthetized rabbits in situ with simultaneous changes in heart rate and blood pressure during 40-s periods of 10%, 5%, 2.5%, and 0% inspired O2 administered sequentially before, during, and after 1% or 1.25% inhaled halothane. Sympathetic efferent nerve activity also was measured, and, in a separate group of animals, measurements were preceded by carotid chemoreceptor denervation. Hypoxia-mediated venoconstriction, bradycardia, and hypertension were attenuated almost equally by both 1% and 1.25% inhaled halothane (the higher dose produced only slightly greater inhibition). These responses were inhibited significantly in chemoreceptor-denervated animals, and the subsequent 1% inhaled halothane added only minimal additional attenuation. Increases in chemoreflex-mediated sympathetic efferent nerve activity also were reduced significantly by (1.25%) inhaled halothane. These results indicate that halothane impairs capacitance vein responses and other hemodynamic adjustments during hypoxia. Inhibition of these compensatory changes appears to be mediated, at least in part, via attenuation of peripheral chemoreflex responses and suppression of the resultant reflex increases in sympathetic efferent nerve activity. PMID- 1416169 TI - Glutathione depletion enhances subanesthetic halothane hepatotoxicity in guinea pigs. AB - Reduced glutathione has a potential role in protecting the liver against the reactive acyl acid chloride intermediate generated during the oxidative biotransformation of halothane. Glutathione is also important in maintaining the integrity of an injured cell. Thus, the effect of decreased hepatic glutathione concentrations on covalent binding of halothane metabolic intermediates to hepatic protein and lipid and the resultant hepatic injury were investigated in male, outbred Hartley guinea pigs. The animals were injected with either 1.6 g.kg 1 dl-buthionine-S,R-sulfoximine to deplete hepatic glutathione or vehicle-control solution 24 h before exposure to 0.1% (subanesthetic) halothane for 4 h (fractional inspired oxygen tension = 0.40). Buthionine sulfoximine pretreatment depleted liver glutathione concentrations by 85% at the time of halothane exposure, without affecting the degree of halothane biotransformation or causing hepatic injury. Glutathione depletion caused a significant increase in the level of organic fluorine covalently bound to hepatic protein but not lipid after halothane exposure. Glutathione-depleted animals also exhibited a significant enhancement of hepatotoxicity after halothane exposure; plasma isocitrate dehydrogenase activity was 25-fold greater than the increase observed 48 h after exposure in animals treated with vehicle plus halothane, and the incidence and severity of hepatic injury were significantly greater, as observed by light microscopic examination of tissue 96 h after exposure. These findings are in agreement with a previously proposed mechanism of halothane-associated hepatotoxicity in guinea pigs and indicate that hepatic glutathione status may play an important role in the susceptibility of patients to halothane-induced liver injury. PMID- 1416170 TI - Cerebral extracellular glucose and lactate concentrations during and after moderate hypoxia in glucose- and saline-infused rats. AB - To assess the effect of a glucose infusion on brain extracellular fluid (ECF) during systemic hypoxia, changes in glucose and lactate concentrations in cerebral ECF during and after moderate hypoxic hypoxia were measured in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were given either saline (n = 6) or 50% glucose solution (n = 6) for 3 h, starting 60 min before the onset of hypoxia. Hypoxia was produced by circulating 7% O2 gas in a plastic chamber for 90 min. In saline-infused animals, brain ECF glucose concentrations decreased slightly during hypoxia, although blood glucose concentrations did not change. Blood lactate concentrations increased to 6.28 +/- 0.91 mM, at 60 min after the onset of hypoxia (P less than 0.05). Brain ECF lactate concentrations increased to 3.53 +/ 0.20 mM and remained constant during 60 min of steady-state hypoxia (P less than 0.05) and decreased to the basal level within 60 min after the end of hypoxia. When sodium lactate solution was infused intravenously for 90 min (n = 4), blood lactate concentrations increased to a level as high as those found during hypoxia. However, the brain ECF lactate concentration increased only to 1.86 +/- 0.09 mM. In glucose-infused animals, the blood glucose concentration reached 339.1 +/- 32.3 mg/dl at the end of the glucose infusion, and the brain ECF glucose concentration increased to 54.7 +/- 7.3 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416171 TI - Effect of progesterone on the cardiac electrophysiologic alterations produced by ropivacaine and bupivacaine. AB - Bupivacaine-induced cardiotoxicity is enhanced in pregnant laboratory animals and in progesterone-pretreated isolated cardiac tissues. Ropivacaine is a new local anesthetic chemically related to bupivacaine. Although clinically equipotent with bupivacaine, ropivacaine is less cardiodepressant. Progesterone levels are elevated during pregnancy, and exogenously increasing progesterone levels in rabbits has increased bupivacaine's depressive effects on excitability. In neural tissues, bupivacaine's increased onset of block and depression of compound action potentials in tissues from progesterone-treated animals was similar to its effect in nerves from pregnant animals. This study determined whether exogenously increased progesterone levels can increase myocardial sensitivity to ropivacaine. Female ovariectomized rabbits were pretreated with progesterone for 4 days. After killing, the hearts were removed and Purkinje fibers (PFs) and ventricular muscle (VM) action potential parameters recorded. Tissues from animals receiving either progesterone or placebo were exposed to either ropivacaine or bupivacaine at concentrations ranging from 3.5 to 18.7 microM. Preparations were routinely paced at 2 Hz except where rate-dependent effects on the maximal rate of depolarization of phase zero (Vmax) were determined. Progesterone increased depression of myocardial Vmax only to bupivacaine (P less than 0.05). Ropivacaine was generally 3-5 times less potent in depressing cardiac electrophysiologic parameters. Bupivacaine demonstrated rate-dependent depression of Vmax that at higher frequencies was greater than ropivacaine's effects (P less than 0.05). Ropivacaine is less cardiodepressant than bupivacaine in this isolated PF-VM preparation. Exogenously increasing progesterone levels in vivo does not increase ropivacaine's depression of myocardial Vmax in isolated PF-VM tissues as it does to bupivacaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416172 TI - Effects of glucose infusion on cerebral cortical glucose and lactate concentrations during endotoxemia in rats. AB - Hypoglycemia has been observed in several species before death from endotoxemia. Although several studies have emphasized the importance of maintaining brain glucose at normal concentration during endotoxemia, the effect of glucose infusion on cerebral glucose metabolism has not been studied. Accordingly, the effects of glucose infusion on interstitial glucose and lactate concentrations in the cerebral cortex during endotoxemia were studied in 22 Wistar rats. Cerebral glucose and lactate were measured at 30-min intervals for 4 h using microdialysis. Animals were divided into four groups: 1) saline-infused control (n = 5); 2) saline-infused endotoxemia (n = 7); 3) glucose-infused control (n = 5); and 4) glucose-infused endotoxemia (n = 5). In groups 2 and 4, endotoxemia was induced by intravenous injection with E. coli lipopolysaccharide B (5 mg.100 g-1). One hour after endotoxin administration, saline or 50% glucose was infused at a flow rate of 0.5 ml.100 g-1.h-1 for 3 h. Endotoxin induced a significant increase (P less than 0.05) in blood glucose in the saline-infused rats, which survived for 4 h (n = 5), from 91.6 +/- 15.4 mg.100 ml-1 at baseline to 136.3 +/- 23.3 mg.100 ml-1 (149%) at 1 h, followed by a gradual decrease (to 63% of the basal concentration at 4 h). Similar changes were observed in brain glucose (14.9 +/- 1.9 mg.100 ml-1 baseline, 175% of baseline at 2 h, and 57% of baseline at 4 h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416173 TI - Physical and chemical properties of drug molecules governing their diffusion through the spinal meninges. AB - Drugs administered into the epidural space for selective spinal analgesia must diffuse through the spinal meninges to gain access to their sites of action in the spinal cord. Therefore, knowledge of the physical and chemical properties of drug molecules that govern their diffusion through the meninges is important for understanding the pharmacokinetics of epidural analgesia. To determine the physicochemical properties of drug molecules that govern the rate at which drugs diffuse through the spinal meninges, the authors measured the permeability coefficient of eight different drug molecules through the spinal meninges of the monkey using a previously established in vitro model. We previously reported permeability measurements for four of the molecules used in this study; the other four molecules' permeability measurements are new. The measured permeability coefficient was then correlated with the drugs' molecular weight, molecular surface area, molecular volume, length of the major molecular axis, and octanol:buffer distribution coefficient. We found no relationship between the drugs' permeability coefficients and any measure of drug mass, molecular shape, or molecular size. There was, however, a biphasic relationship between the octanol: buffer distribution coefficient and the drugs' measured permeability coefficients. Drugs that were either very hydrophilic or very hydrophobic had permeability coefficients that were significantly less than drugs of intermediate hydrophobicity. These data suggest that it should be possible to design novel analgesics for which meningeal permeability is maximal. PMID- 1416174 TI - Comparison of the antinociceptive effects of pre- and posttreatment with intrathecal morphine and MK801, an NMDA antagonist, on the formalin test in the rat. AB - Current thinking emphasizes that protracted small afferent input can evoke mechanisms that mediate a significant potentiation of spinal nociceptive processing and that this facilitory component has a unique pharmacology. To investigate the behavioral parallels of this spinal facilitation, we evaluated the effects of pre- and post-treatment of intrathecal morphine (mu agonist) and MK801 (N-methyl-D-aspartate [NMDA] antagonist) on the formalin test. Intraplantar formalin resulted in a biphasic appearance of flinching behavior (phase 1 = 0-5 min; phase 2 = 10-60 min). Morphine and MK801 were administered intrathecally 15 min before formalin injection in the pretreatment study and 9 min after formalin injection in the posttreatment study. Pretreatment with intrathecal morphine produced comparable dose-dependent suppressions of the phase 1 and phase 2 behaviors (ED50 = 0.5 micrograms [95% CI = 0.3-0.9] and 0.3 micrograms [95% CI = 0.1-0.7], respectively). Posttreatment with morphine also resulted in comparable suppression of the phase 2 response (ED50 = 0.2 micrograms [95% CI = 0.1-0.3]). At the highest dose of intrathecal morphine (10 micrograms), an almost complete suppression of formalin-evoked behavior was observed. Pretreatment with MK801 inhibited the second-phase response more strongly than the first-phase response (ED50 = 1.6 micrograms [95% CI = 0.5-5.7] vs. 0.1 microgram [95% CI = 0.3 - 0.4], respectively). In contrast, posttreatment with the highest dose of MK801 had no effect on the phase 2 response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416175 TI - The role of neutrophils, oxidants, and proteases in the pathogenesis of acid pulmonary injury. AB - We recently reported a biphasic injury pattern of nonlethal acid aspiration pneumonitis in rats. The first phase consisted of the immediate effects of the direct tissue injury, and the second phase was associated with a neutrophilic inflammatory response. Using this model, the present report examines the possible role of neutrophils, oxidants, and proteases in the pathogenesis of the second phase of this lung injury. Acid aspiration injury was induced by instillation of saline/HCl, pH = 1.25, into the trachea of rats. Lung injury was assessed by measuring the degree of alveolar capillary permeability to 125I-labeled albumin (permeability index [PI]). Rats made neutropenic with polyclonal antineutrophil antibody had a lower PI (0.44 +/- 0.07, P less than 0.05) 6 h after acid aspiration than similarly injured animals with normal whole blood neutrophil counts (PI = 0.85 +/- 0.03). Even though neutrophils appeared necessary for the full development of the lung injury in this model, the administration of different intravenous and/or intratracheal concentrations of either deferoxamine or catalase offered no protection against injury. This suggests that neutrophil oxidants were minimally involved in the injury. Large increases in leukocyte-free serine protease activity (1,477 +/- 438 u/ml, P less than 0.05) were detected in the bronchoalveolar lavage fluid from the saline/HCl, pH = 1.25, injured rats at 6 h postinjury, as compared to saline/HCl, pH = 5.3, treated control animals (2.7 +/- 0.2 u/ml). This study supports the hypothesis that neutrophils are necessary for the full expression of acid-induced lung injury and that the generation of leukocyte-derived oxidants does not appear to be the primary mechanism involved in this injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416176 TI - Reversal of neuromuscular blockade. PMID- 1416177 TI - Controlled substance dispensing and accountability in United States anesthesiology residency programs. AB - Controlled substance dependence (CSD) among anesthesiology personnel, particularly residents, has become a matter of increasing concern. Opinions vary as to the effectiveness of controlled substances (CS) accountability in deterring, identifying, or confirming CSD. A survey of program directors of American anesthesiology training programs was conducted in the summer of 1990 to determine the level of CS dispensing and accountability within their programs. The survey demonstrated that CS dispensing and accountability varied considerably among programs, among hospitals associated with individual programs, and within geographically distinct anesthesia delivery areas within the separate hospitals. Nevertheless, most institutions were moving toward improved methods of CS dispensing and providing more and better CS accountability. The presence of significant CSD, particularly among anesthesiology residents, was reconfirmed. We were unable to correlate the level of accountability of CS with the incidence of CSD. It remains to be seen to what extent CS accountability will continue to develop and whether CSD prevalence will then be changed. PMID- 1416178 TI - Michael Faraday and his contribution to anesthesia. AB - Michael Faraday (1791-1867) was a protege of Humphry Davy. He became one of Davy's successors as Professor of Chemistry at the Royal Institution of Great Britain. Of Faraday's many brilliant discoveries in chemistry and physics, probably the best remembered today is his work on electromagnetic induction. Faraday's contribution to introduction of anesthesia was his published announcement in 1818 that inhalation of the vapor of ether produced the same effects on mentation and consciousness as the breathing of nitrous oxide. He most likely became familiar with the central nervous system effects of nitrous oxide through his association with Davy, an avid user of the gas. Sulfuric ether was a common, convenient, cheap, and easily available substance, in contrast to nitrous oxide, which required expensive, cumbersome, and probably not widely available apparatus for its production and administration. The capability for inhaling intoxicating vapors eventually became commonly available with the use of ether instead of the gas. The first surgical anesthetics were a consequence of the resulting student "ether frolics." The 1818 announcement on breathing ether vapor was published anonymously; however, notations in Faraday's handwriting in some of his personal books clearly establish Michael Faraday as the author of this brief communication. PMID- 1416179 TI - Anesthesiologist addicted to propofol. PMID- 1416180 TI - Fentanyl dependence associated with oral ingestion. PMID- 1416181 TI - Isolated masseter muscle spasm and increased creatine kinase without malignant hyperthermia susceptibility or other myopathies. PMID- 1416182 TI - Tight mask fit could have prevented "airway" obstruction. PMID- 1416183 TI - Orotracheal intubation of an infant with hemifacial microsomia using a modified lighted stylet. PMID- 1416184 TI - Propofol tolerance in a pediatric patient. PMID- 1416185 TI - Shakespeare speaks to anesthesiologists. PMID- 1416186 TI - Contamination of propofol. PMID- 1416187 TI - Mechanisms for effective dissemination of critical information. PMID- 1416188 TI - A potentially serious complication that resulted from improper use of the Univent tube. PMID- 1416189 TI - Lower extremity neuropathy after laparoscopic cholecystectomy. PMID- 1416190 TI - Use of the capnograph to detect leaks in the anesthesia circuit. PMID- 1416191 TI - Electroencephalographic effects of sedative hypnotics. PMID- 1416193 TI - [Characteristics of the metabolic disorders during prolonged craniofacial surgery]. AB - Brain and liver metabolism has been studied by selective probing of vessels collecting blood from the brain and liver, in 95 patients with various surgical craniofacial pathology. Prolonged general anesthesia in craniofacial traumas has a negative effect on brain metabolism. Changes in indispensible amino acid formulas and hypoxia may cause the loss of brain circulation autoregulation and damages in central mechanisms regulating metabolic processes. A complex scheme of metabolism correction during prolonged anesthesia in craniofacial surgery is suggested. PMID- 1416192 TI - [The effect of indomethacin and leukinferon on the level of blood plasma thromboxane B2, platelet aggregation and the immune system of patients with endometrial cancer in the perioperative period]. AB - The perioperative influence of leukinferon, indomethacin and their combination on the blood plasma level of thromboxane B2 (TxB2), platelet aggregation ability and humoral and cellular immunity has been assessed in 40 endometrial cancer patients. It has been found that the perioperative use of indomethacin diminishes the blood plasma level of TxB2 and platelet aggregation ability. Leukinferon did not affect substantially the parameters. However, the combination of leukinferon with indomethacin causes a more stable reduction in platelet aggregation and TxB2 level than the use of indomethacin alone. The use of these drugs and their combination prevented postoperative immune suppression in the endometrial cancer patients. However, leukinferon alone or its combination with indomethacin were more effective than the use of indomethacin alone. Possible mechanisms of indomethacin and leukinferon effect on tumor cell metabolism of arachidonic acid and possible role of eicosanoids in the pathogenetic mechanisms of tumor growth and metastasis dissemination are discussed. PMID- 1416194 TI - [The effect of droperidol on heart function]. AB - The effect of droperidol (3.3 x 10(-6) M) on the functional capacities of the isolated heart has been studied. The drug inhibited myocardial contractility. The effect manifested directly after the introduction of droperidol into perfusate (prompt phase). Afterwards the progress of the drug inhibitory effect was slow (slow phase). It is assumed that the difficulties in the use of droperidol in the critical cardiosurgical patients are associated with the attenuation in the realization of the regulatory effects of the central nervous system. PMID- 1416195 TI - [Clinical aspects of the use of nubain, tramal and moradol in patients in the early postoperative period]. AB - Opioid analgesics were used in 282 patients on the first-third day after heart, lung and abdominal surgery. The main indication for their use was pain syndrome. Adequate analgesia with tramal, nubain and moradol was noted in 73, 76 and 81% of cases. In marked pain syndrome after thoracotomy the most effective agents were moradol and morphine. Computer monitoring of the respiratory function in tramal analgesia has shown a decrease in lung ventilation, esophageal pressure, inhalation volume, O2 production. Tramal, nubain and moradol in analgesic doses did not inhibit respiration. In adequate analgesia there was a decrease in lung ventilation which was not accompanied by shifts in acid-base balance of the arterial blood. The above analgesics had no considerable effect on systemic hemodynamics, though the use of tramal decreased systemic blood pressure and the use of moradol decreased systemic blood pressure and total peripheral vascular resistance. Tramal was most effective for synchronization of spontaneous respiration with a lung ventilation device in prolonged ventilation, as well as for the arrest of muscular tremor in the postoperative period. Tramal was effective in 95% of patients in the early post-anesthesia and postoperative period. PMID- 1416196 TI - [The effect of tramal and acupuncture analgesia on labor pain and the psychoemotional status of the parturient]. AB - The intensity and structure of pain during delivery as well as changes in psychoemotional status have been studied in 65 women with reference to the use of concomitant correcting therapy during various types of analgesia. 44 women comprised a control group. It has been found that acupunctural analgesia was optimal during delivery without any correcting therapy, while tramal (at a dose of 1.43 +/- 0.06 mg/kg) was optimal during "programmed" delivery. PMID- 1416197 TI - [Morphologic changes in the tracheal mucous membrane following aspiration of the gastric contents]. PMID- 1416198 TI - [Changes in the concentration of beta-endorphin in the cerebrospinal fluid due to morphine analgesia in incurable oncologic patients]. AB - Thirty cancer patients, clinical group IV, have been examined. It has been established that a persistent pain syndrome leads to lowering in beta-endorphin liquor level. Morphine analgesia is followed by beta-endorphin level elevation which directly depends on pain intensity and analgesia efficacy. Determination of changes in beta-endorphin liquor level may serve as a criterion of analgesia efficacy. PMID- 1416199 TI - [The effect of infusion therapy on the ventilation-gas exchange function of the lung during acute destructive pneumonia in young children]. AB - It has been established that respiratory failure in young children with destructive acute pneumonia was enhanced upon intravenous correction of homeostasis disturbances with daily physiological volume repletion. Combined enteral-parenteral correction of homeostasis disturbances was an alternative technique. PMID- 1416200 TI - [Immunologic indices in patients with sepsis and their changes in response to complex intensive therapy]. AB - Immune status has been studied in the course of intensive care in 48 patients. It has been established that hemosorption may enhance already existing changes in immune homeostasis in patients with sepsis. Therefore, immunostimulating therapy with tactivin and group B vitamins (B1, B6, B12) or ultraviolet (UV) blood irradiation in combination with group B vitamins administration have been included into therapy. Simultaneous use of tactivin, group B vitamins and UV blood irradiation was not advisable due to reduction of immunostimulating effect. Consecutive use of the immunity-stimulating methods seems expedient. PMID- 1416201 TI - [The immunoprotective effect of ceruloplasmin in the acute period of patients in critical conditions of different origin]. AB - Cellular immunity and opsono-phagocytic system have been studied in acute period in 23 critically ill patient. The immunoprotective effect of an antioxidant ceruloplasmin (800-1000 mg/day) has been assessed. It has been found that along with correction of antioxidant potential, ceruloplasmin promoted the retention of opsono-phagocytic system activity. Direct immunoprotective effect of ceruloplasmin was confirmed in vitro. PMID- 1416202 TI - [The functional status of the sinoatrial node and the atrioventricular conductivity in patients with acute klofelin poisoning]. AB - Using diagnostic transesophageal electrical cardiostimulation, sinus node function, sinoatrial and atrioventricular conductivity have been studied in 30 patients with acute clophelin poisoning. The results of pharmacological tests with atropine and alupent are presented. Control examinations have been performed on discharge. The results of pharmacological tests have shown that clophelin effect could be realized via imbalance of autonomous heart innervation. The technique of diagnostic transesophageal electrical cardiostimulation is recommended for wider use in clinical toxicology. PMID- 1416203 TI - [The use of klofelin in general anesthesia]. PMID- 1416204 TI - [The contractility of the lower portion of the esophagus as a criterion of the adequacy of anesthesia]. AB - It has been found that narcotic analgesics (morphine, fentanyl and dipidolor), inhalation anesthetics (phthorothan and frilen) and an intravenous anesthetic calypsol suppress lower esophageal contractility. Comparison of lower esophageal contractility with hemodynamic parameters and ACTH and cortisol blood plasma content have revealed a direct correlation. It is concluded that the method of dynamic control over lower esophageal contractility may be an objective test controlling the adequacy of anesthesia during various surgical interventions. PMID- 1416205 TI - [Anesthesia in emergency surgery on the organs of the hepato-pancreato-duodenal area in elderly and aged patients]. AB - One hundred and two male and female patients, aged 65-85 years, have been examined. All of them had been subjected to urgent surgery for acute surgical pathology of the organs of hepatopancreatoduodenal area. Surgery was performed under one of the following anesthesia techniques: neuroleptanalgesia, epidural anesthesia (EA), combination of EA and endotracheal anesthesia. Changes in central hemodynamics, acid-base balance and oxygen balance parameters have been studied in the preoperative, intraoperative and early postoperative period. The advantages of a combined technique which ensures optimal conditions for the maintenance of circulatory and oxygen homeostasis have been proved. PMID- 1416206 TI - [Infusion-transfusion tactics in tubercular surgical patients in relation to the volume of surgical blood loss]. AB - Infusion-transfusion tactics were studied in 71 patients with pulmonary tuberculosis during surgery and after it. Hemostasis parameters have been determined at different periods after surgery. Blood transfusion was not performed in patients with surgical blood loss below 500 g. When surgical blood loss was 500 to 1000 g hemotransfusion volume was 40-50% of blood loss. When surgical blood loss was 1000 g the volume of blood substituting solutions exceeded blood loss 2.4-4 times; in massive blood loss it was 1.5 times more. For the first 24 hours after surgery the volume of infusion-transfusion therapy was maintained at the same level, with its decrease 48 and 72 hours later. Such tactics promoted a favourable clinical course of the postoperative period and stabilization of basic homeostasis parameters. PMID- 1416207 TI - [Non-inhalation anesthesia with preservation of spontaneous breathing in emergency surgery in children]. AB - A total of 320 patients with acute abdominal surgical pathology were examined after general anesthesia with combined intravenous injection of sodium hydroxybutyrate and calypsol, with spontaneous respiration preserved. The examinations were performed under clinical control and impedance plethysmography. The combination of the above anesthetics has a lot of advantages over calypsol mono-anesthesia and ensures adequate blockade of visceral innervation. A slight circulatory hyperdynamia has been observed. This type of analgesia is one of the optimal methods of general anesthesia in children. PMID- 1416208 TI - [Successful use of a bronchofibroscope in jet lung ventilation of tracheal stenosis]. PMID- 1416209 TI - [The volume of circulating blood during surgery of the aorta performed under epidural anesthesia]. AB - Various methods of circulating blood volume (CBV) determination have been compared. The calculation method based on anthropometric to hemodynamic parameter ratio was shown to be optimal during surgery on the aorta and major vessels. Epidural anesthesia in 15% CBV deficit in the preoperative period and anesthetic administration into the epidural space intraoperatively in 10% CBV deficit were contraindicated. Epidural anesthesia caused CBV reduction, with its maximum changes observed upon blood flow recovery in the vascular bed. 10-15 ml/kg, 15-20 ml/kg and 20-30 ml/kg blood loss was 2.5,3 and 3.5 times overcompensated, respectively. PMID- 1416210 TI - [The pulmonary distress syndrome during acute arterial occlusion of the lower extremities]. AB - After surgery for acute arterial occlusion in the lower extremities 59 patients have developed tachypnea, respiratory alkalosis and arterial hypoxemia. These symptoms persisted over the whole postoperative period. In 66% of dead patients pulmonary changes have been observed and only in 34% of patients who died suddenly the lungs were unaffected. Morphological changes in the lungs are most marked in long-standing ischemia and have the signs of the "shock lung" (adult respiratory distress syndrome). Pronounced changes in the respiratory function, acid-base balance, blood gas composition can account for a more severe course of the disease, deteriorate the prognosis, predetermine multiorgan failure in the early postoperative period. PMID- 1416211 TI - [Awake tracheal intubation--a method of choice in patients at risk of aspiration of gastric contents]. AB - The experience gained with awake tracheal intubation in 39 urgent surgical patients at risk of gastric contents aspiration is presented. After standard premedication fentanyl (4.5 micrograms/kg) was injected, local anesthesia of the root of the tongue, epiglottis and vocal cords was performed with 10% lidocaine spray, rohipnol (0.032 mg/kg) and muscular relaxants were administered and controlled lung ventilation was started. Four patients had vomiting, in 5 patients fentanyl caused muscular restraint. No failures have been observed. Indications for awake tracheal intubation and drawbacks of fentanyl injections are discussed. Awake tracheal intubation prevented effectively aspiration due to retention of coughing and guttural reflexes. PMID- 1416212 TI - [Electroacupuncture stimulation in the treatment of postoperative disorders of the motor-evacuatory function of the stomach and intestines]. AB - One hundred and eight patients with gastric ulcer subjected to planned and urgent surgery have been treated for postoperative gastric atonia and intestinal paresis using electroacupuncture stimulation (EAPS). The treatment was effective in 85% of cases, with the efficacy confirmed by clinical results and gastroenterologic findings. EAPS promoted a decrease in the initially high blood levels of cortisol, aldosterone and histamine, an increase in serotonin and a reduction in gastric juice histamine levels, which were indicative of the analgetic and antihistamine EAPS effect and attenuation of parasympathetic activity. EAPS introduction into a complex of postoperative rehabilitation procedures led to reduction of drug doses or total drug replacement, early activation of surgical patients and prompt recovery of normal gastrointestinal evacuation. PMID- 1416213 TI - [The interaction of moradol (butorphanol tartrate) and flormidal (midazolam) in the patient's body]. AB - Twenty five female patients (3 groups) operated on for cholelithiasis without premedication have been examined. In patients of group F an effective flormidal dose (EFD) causing an unconscious state upon intravenous injection by a measuring device has been determined. Due to an insufficient sedative effect of moradol it was impossible to determine an effective moradol dose (EMD). In group M+F right after intravenous administration of a standard moradol dose (SMD) flormidal infusion was begun, as in patients of group F. EFD after moradol injection (EFMD) was determined. Making proportions with known EFD, EFMD and SMD values, EMD was calculated. Upon intravenous administration of the calculated EMD by a measuring device the sedative effect was superficial in all the patients of group M and it was impossible to achieve an unconscious state. The interaction of moradol (butorphanol tartrate) and flormidal (midazolam) in the patients' body is of synergic nature. PMID- 1416215 TI - [Blood viscosity disorders and their pathogenetic significance in anesthesiology]. PMID- 1416214 TI - [A case of successful treatment of a severe form of suppurative meningitis]. AB - A patient with severe meningoencephalitis has been treated using a combination of generalized and local mechanisms of antibacterial drug delivery to the inflammation focus, detoxication and brain circulation improvement. The management results have been analysed. Positive neurological dynamics, homeostasis recovery and shorter period of the patient's stay in an intensive care unit proved the efficacy of management. It is assumed that the improvement of brain perfusion is an important pathophysiological mechanism. PMID- 1416216 TI - [Hyperbaric oxygenation and antianginal preparations: the effect of a single combined use on the functional indices of the state of the heart in patients with angina pectoris]. AB - Using electrocardiographic technique, the effect of a single hyperbaric oxygenation session (O2 pressure 1.5 atm, duration 40 min) in combination with antianginal drugs (nifedipine--20 mg, propranolol--40 mg, nitrong--6.5 mg, orally) on central hemodynamics and myocardial contractility has been studied in 35 patients with ischemic heart disease and angina pectoris of effort, NYHA functional class II-III. It has been shown that hyperbaric oxygenation reduced the degree of indirect hemodynamic effect of nifedipine, potentiated negative chronotropic and inotropic effects of propranolol and had no impact on the degree of hemodynamic effect of depot-glycerol trinitrate. PMID- 1416218 TI - Musculo-skeletal pain (MSP) in onchocerciasis: a potential in the rapid low cost epidemiological survey and in the assessment of impact of ivermectin treatment on a community. AB - The diagnostic potential of musculo-skeletal pain (MSP) in the rapid assessment of onchocerciasis of morbidity and of the impact of ivermectin treatment in a community is brought to picture. The clinical impression is that MSP is a common, early, chronic important symptom of onchocerciasis. With a significant association with onchocerciasis, MSP has the potential of being an important operational diagnostic clue in the detection of onchocerciasis. It has the advantage of being easily recognizable, and therefore can be applied by primary health care workers. MPS is proved to cause the greatest morbidity, particularly among working farmers in areas where the forest strain of O. volvulus is predominant. Thus, onchocerciasis is contributing more than was perhaps realized to the reduced output of work from farmers. However, MPS, a parasitic rheumatism, is proved to be eminently susceptible to treatment by DEC. PMID- 1416217 TI - Filariasis in Gongola State Nigeria. I: Clinical and parasitological studies in Mutum-Biyu District. AB - A total of 2,552 persons living in 9 villages along the Benue river valley, Mutum Biyu district of Gongola State, Nigeria were examined between October and December 1989 for filariasis. It is the first time a filariasis survey will be carried out in this state. 276 (10.8%) had Wuchereria bancrofti, 50 (2.0%) had Loa loa, 281 (11.0%) were positive for Mansonella perstans while 12 (0.5%) were positive for Onchocerca volvulus. Villages located near the Benue river had higher prevalence rates than those further away. Dermatitis and hydrocoele were common and clinical manifestations were associated with parasite types. Clinical symptoms without microfilaremia and microfilaremia without clinical symptoms were also observed. PMID- 1416219 TI - Experimental Wuchereria bancrofti infection of Culex quinquefasciatus and Aedes aegypti. AB - Laboratory-derived females of Culex quinquefasciatus and Aedes aegypti were experimentally infected with Wuchereria bancrofti by allowing the insects to feed on infected volunteers of known microfilariae density between 24.00 and 2.00 hours. Of the 240 mosquitoes used for the experiments only 67 (55.8%) of C. quinquefasciatus and 83 (69.2%) of the Ae.aegypti actually fed on the volunteers' blood. After 16 days post-infection period, 50 (74.62%) of the engorged C. quinquefasciatus harboured infective L3 larval stages of W. bancrofti, while 16 (23.9%) and 1 (1.49%) harboured L2 and L1 pre-infective larval stages, respectively. On the other hand, no development to the L3 infective stage was observed in the engorged Ae.aegypti though 34 (40.96%) harboured L1 pre-infective stages of the parasite. Our results suggest that C.quinquefasciatus could be actively involved in the transmission of urban bancroftian filariasis in Nigeria. PMID- 1416220 TI - [Extent and course of excretion of larva in the milk of female dogs after infections of different severity with Ancylostoma caninum (Ancylostomatidae)]. AB - It was investigated whether there is a linear correlation between the number of applied infective larvae of Ancylostoma caninum and the number of larvae excreted by bitches with the milk. The investigations were carried out with nine bitches that were infected percutaneously each with 5,000, 10,000 or 20,000 third stage larvae of Ancylostoma caninum at the day of conception. A clear linear correlation between the number of applied infective larvae of Ancylostoma caninum and the number of larvae excreted with the milk could be demonstrated only for the first week of lactation. Regarding the total investigated period of 28 days only a tendency towards such a correlation between infective dosage and excretion of larvae with the milk could be found. PMID- 1416221 TI - [Determination of parasite-specific antibodies during human schistosomiasis- diagnostic relevance]. AB - Sera from patients with schistosomiasis (Schistosoma mansoni or S. haematobium) were examined for the presence of parasite specific antibodies (total antibodies), specific IgE and IgG4 antibodies by means fo ELISA technique using antigens prepared from adult worms of S. mansoni. Individuals from tropical countries who had no schistosomiasis and blood donors from Germany were studied for comparison. Significantly higher levels of specific antibodies were given by sera from patients with schistosomiasis than by controls in the tests for total antibodies, IgE and IgG4. The use of these results in diagnosis is compared and assessed with microscopic-parasitological methods. PMID- 1416222 TI - [The improvement of polyxenic cultivation of Entamoeba histolytica type HK 9]. AB - The serological diagnosis of extraintestinal infections with E. histolytica by indirect immunofluorescence (IFAT) requires a corpuscular antigen. This is produced in our laboratory via polyxenic cultivation of E. histolytica strain HK 9 in a nutrient medium containing a simple salt mixture (Resembling the Ringer mixture), calf serum and rice starch. It was the aim of the experiments described in this paper to search for a useful medium in which the amebae grow in high density but without substances disturbing the antigen production like debris or rice starch granules. It was shown that the cell culture media of EAGLE MEM and PARKER were easy to handle (contrary to the worldwide used DIAMOND medium TYI-S 33) and brought good results. After a period of 10 subcultures both media were suitable for the cultivation of E. histolytica for making an antigen reasonable for IFAT. As a side effect it was noticed that there was an adaptation phase during which the amebae grew slowly when the medium was changed to another which was completely different (from a cell culture medium to a Ringer-like solution). PMID- 1416223 TI - [Short term cultivation of Plasmodium for the determination of chloroquine resistance]. AB - The in-vivo-test of Plasmodium drug resistance is one of the essential basic controls, assisting therapeutic measures in tropical malaria. An initial in-vitro check up of drugs provided for antimalarial therapy is another useful help to the clinician. Even when manufactured WHO test kits are not available, the analysis of drug resistance can be performed under simple working conditions. Its application is demonstrated in a patients history. PMID- 1416224 TI - [Inflammation of the dura mater following tick bites in Sweden: protective vaccination recommended for travel to Sweden]. PMID- 1416225 TI - [The tick fauna of eastern Germany]. AB - The occurrence of several tick species in selected areas of Eastern Germany is described. From May 1987 till December 1989 8,472 ticks from 430 places were examined. Ixodidae of the genus Ixodes, Dermacentor and Haemaphysalis as well as Argasidae of the genus Argas were identified. The most common species was Ixodes ricinus. Furthermore, an endemic area of Dermacentor reticulatus was detected in the Duben-Dahlen and Annaburg health. Two other species of ticks, which were found frequently and sometimes with a high intensity on the host were Ixodes hexagonus and Ixodes canisuga. On the other side the species Haemaphysalis concinna and Argas vespertilionis were present at only one respectively two places and with a low population density. PMID- 1416226 TI - [Calf carotids in experimental vascular surgery]. AB - Use of calf [correction of sheep] carotids maintained on 98% glycerol is described as a material of substitution of aorta and femoral arteries in the dog, in experimental surgery. Taking, maintenance and application technics of such heterografts are described. Also, histology after 24 months following the surgical procedure was studied in 10 cases of dog aortic grafts and its results are presented. PMID- 1416227 TI - [The treatment of vasospastic disease by chronic spinal cord stimulation. A case report]. AB - In 1976, by first time, Cook used the chronic medullar stimulation (CMS) for the treatment of chronic arteriopathies at the limbs in patients with distal ischemic ulcerations. Up to now, some studies about this procedure have been published. Results, poor at first, have presented an important improvement with the time and the better choosing of patients. In 1981, Neglio used by first time CMS as a treatment of vasospastic disease, with excellent results. With this procedure, pain and vasospastic crisis disappeared and re-epithelialization of ischemic ulcerations is found. In this article, we presented a case interesting because it show the different possibilities of this method as a symptomatic treatment of such kind of disease. Patient, with a Raynaud syndrome secondary to an sclerodermia treated previously by medical and surgical procedures, was treated, in different times, with CMS because of digital ischemic ulcerations in both hands. Results were positives and ulcerations healed. PMID- 1416228 TI - [The arterial complications of closed injuries to the shoulder girdle]. AB - After a period of time of 5 years, we made a review of all the patients registered at our Center. Eight cases of closed traumatism at the scapulohumeral belt, with vascular injury associated (0.2% of all closed traumatisms at this level registered in our center during this time) were reported. Six patients presented also an osteoarticular injury associated. Three different vascular injuries were showed: three cases of complete arterial section, two arterial contusions and a partial arterial section. From the two cases without osteoarticular injuries, one of them showed a complete section and the other presented an arterial contusion. Polytraumatic patients showed multiple osteoarticular injuries. We registered one fracture-luxation at the shoulder, 3 diafisaric humeral fractures, one humeral neck fracture, one clavicle fracture, one fracture-luxation at the cervical column and one simple luxation of the shoulder. PMID- 1416229 TI - [The use of the Gott shunt in the surgical repair of a dissecting aneurysm of the descending thoracic aorta]. AB - A 49-years-old man was operated on of a descending thoracic dissecting aneurysm by means of a heparin-less external Gott shunt. A review of spinal irrigation, neurological deficits postclamping of the descending thoracic aorta and methods of spinal preservation in aortic surgery are presented. PMID- 1416230 TI - [An oxygen study of patients with chronic ischemia of the lower extremities]. PMID- 1416231 TI - [The past, present and future of lumbar sympathectomy]. AB - The ischemic extremities treatment in a precarious phase has been standardized in the two last decades with a significance extremities savement. But the ischemia of the interdigital vessels and at the microcirculation is still a defiance. We expose the hiperemiant surgery past. We describe the experience of four years in Centre Hospitalari-Unitat Coronaria, Manresa, with 21 lumbar sympathetic ablation in patients without distal pulse, ankle/arm index by Doppler effect between 0 and 0.6 and angiographies without distal bed images, with 13 successes, 2 exitus by M.A.I., 3 amputations and a lung edema. We finish with a futuristic vision that suggest alternatives for the usage of the lumbar sympathectomy according to the medical advances in the coming time for available the ischemic extremities. PMID- 1416233 TI - The quality driven practice. PMID- 1416232 TI - [Reinterventions for the late failures of femoral-distal grafts]. AB - In this retrospective study of 195 patients treated for late failure of a previous femoral-distal reconstruction, there were 178 men and 17 women ranging in age from 42 to 79 years. The graft material utilised for initial operation was an autogenous vein reversed saphenous vein (75), in situ (1), and arm veins (4) in 80, polytetrafluoroethylene in 51, Dacron in 46, Biografts in 12 and composite grafts in 6 patients. The previous site for distal anastomosis was above the knee in 79, and tibial or peroneal arteries in 18 cases. The most common cause of graft failure was late thrombosis (95), progression of the underlying disease (64), deterioration of the graft (15), pseudoaneurysms (8), and rarely perigraft reactions, hemodynamic insufficiency, late infection, etc. The aim of the reoperation was: graft extension for distal disease (68) desobstruction and patch angioplasty (21), thrombectomy (9) exchange of the graft (17), local repair of the graft (3). Seventeen patients required inflow procedures. Other reinterventions (sympathectomy, catheterisation and prostaglandin perfusion) were used in patients with no chance for reconstructive arterial surgery. Secondary reoperations were performed in 12, tertiary operations in 7 patients. Major amputations rate, operation mortality, wound morbidity and hemodynamic success rates with limb salvage in reoperated patients support usefulness of repeated revascularisation when femoro-distal bypass failure occurs. PMID- 1416234 TI - Support for "pathology rationale" for orthodontic treatment. PMID- 1416235 TI - Estimated and true hinge axis: a comparison of condylar displacements. AB - The purposes of the investigation were: i) to compare the condylar displacements from centric slides for 74 sets of casts mounted with an estimated versus a true hinge axis; ii) to determine the error in hinge axes location on the recording of condylar displacements from centric slides; and iii) to define the reproducibility of the Mandibular Position Indicator (MPI), a method of measuring condylar (in vitro) displacements from centric relation position. The findings revealed that routine use of the true hinge axis to obtain MPI readings for analysis of diagnostic casts is not warranted. The mean standard error of MPI double readings attributed to both hinge axes location was 0.4 mm for each component in the sagittal plane. Of the 0.4 mm of mean standard error, 0.2 mm was contributed by the lack of reproducibility of the MPI. The centric relation bite registration technique outlined in this study always captured a superior articulator position of the condylar mechanism. The condylar distractions and deflections from centric relation to maximum intercuspation were primarily in an inferior direction with a smaller posterior component. PMID- 1416236 TI - Assessment of buccal separators in the relief of bruxist activity associated with myofascial pain-dysfunction. AB - The purpose of this study was to evaluate the effectiveness of heavy (S2) Alastik separators in relieving bruxist activity as monitored through masseter muscle area EMG activity, muscle palpation, and self-reporting in 21 Caucasian subjects. The subjects, all of whom suffered from both bruxism and myofascial pain dysfunction, were randomly assigned to one of three groups: experimental (separator group); placebo (separator placed and removed); and control groups (no separator). The findings from this study indicate that there were no observable differences in either subjective or objective responses to the pretreatment versus posttreatment questionnaire and clinical examination for tooth clenching or grinding, facial pain, and fatigue of the jaws. In addition, no statistical differences were found between pre and posttreatment data. The EMG data did not show any statistical differences between pretreatment and posttreatment evaluations or among the 3 groups. PMID- 1416237 TI - Facial growth during adolescence in early, average and late maturers. AB - The relative stage of maturity of a child may be determined by comparing the child's hand-wrist radiograph to known standards of skeletal development. Hand wrist radiographs of 70 adolescents were used to categorize the individuals by skeletal maturation into early, average and late maturation groups using the Fishman SMA method of assessment. The rates of mandibular and maxillary growth relative to the last stages of the pubertal growth spurt were measured. Statistical evaluation of the data was performed using an analysis of variance. The magnitude of change in growth increments of the mandible was greater in the late maturers than in the early or average maturers. Incremental differences in growth between the maxilla and mandible during the last stages of puberty were noted, with the mandible growing significantly more than the maxilla. PMID- 1416238 TI - Force generation by orthodontic samarium-cobalt magnets. AB - The use of samarium-cobalt (Sm-Co) magnets for light force application is a relatively new concept in orthodontic tooth movement. This study reports on the forces generated by these magnets. Magnets were attached to aluminum rods mounted in a universal testing machine. The magnets were initially separated by 10 mm were moved toward each other at 2.5mm/min in repulsion or attraction, depending upon the magnetic pole orientation. The magnets were also positioned initially in contact and then moved apart at a rate of 2.5mm/min, again producing repulsion or attraction, depending upon the pole orientation. The Sm-Co magnets exhibit very large forces when in close approximation but forces decrease markedly at separations greater than 2mm. The force, P, generated between magnets is determined by their separation, d, and follows the relationship P = dn. At magnet separations of 0 to 2mm, the exponent n is equal to -0.4; at separations of 2mm to 7mm, exponent n equals -2.1 for both attraction and repulsion. Thus the classic Coulomb law of magnetic force was followed only at magnet separations of greater than 2mm. Force-separation behavior and the high cost of these magnets may not justify their routine clinical use. PMID- 1416239 TI - Force magnitude effects upon osteoprogenitor cells during premaxillary expansion in rats. AB - To study the effects of force magnitude on osteoprogenitor cell activity during premaxillary expansion, stainless steel helical springs were attached to the maxillary central incisors of 45 3-month-old male rats. The animals were randomly divided into force levels (0, 50, 100, 150, 200 gm) and were injected intraperitoneally with tritiated thymidine (1.0 uc/g wt.) 1 hour prior to sacrifice which occurred at 27, 40, and 60 hours. In order to examine cell activity within different regions of the suture, each premaxilla was divided into three geographic areas. Quantitative results were obtained by comparing the percent of labeled cells observed at different force levels, geographic areas, and observation times. The greatest number of labeled cells at each force level was found at 27 hours. Increased forces were correlated with increased numbers of labeled cells up to 100 gm, with decreased cell numbers at higher forces. The numbers of labeled cells at 200 gm were not significantly different from the controls. Histological observations of early bone formation at 60 hours supported the quantitative labeling results at 27 hours. The results also demonstrate a significant correlation between the geographic location of the labeled cells and force magnitude, with maximal cell stimulation occurring more superiorly in the suture as forces increased. The results suggest that early bone formation within the expanded suture can be maximized by varying force magnitude and distance from the point of force application. PMID- 1416240 TI - Childhood and pubertal growth changes of the human symphysis. AB - Longitudinal growth changes of the human symphysis were evaluated for 75 children (37 males and 38 females) between 6 and 15 years old. Childhood growth was described by mean yearly rates of change between 6 and 10 years for females and between 7 and 11 years for males; pubertal changes pertain to growth between 10 and 14 for females and between 11 and 15 for males. Cephalometric tracings of the mandible were superimposed using stable reference structures. Vertical growth changes, particularly for landmarks located in the upper 20% of the symphysis, were most pronounced. Annual rates of vertical growth ranged between 0.9 mm/yr for the lingual incisor contact point to -0.2 mm/yr for gnathion. Males showed significantly greater rates of vertical growth than females, especially for the upper half of the symphysis. Vertical growth rates were also greater during puberty than during childhood. The horizontal growth changes indicated lingual movement of most symphyseal landmarks. Annual rates of growth were greatest for landmarks located in the upper half of the symphysis. B-point showed the greatest lingual drift. During puberty, the mandibular incisors in females moved lingually as the upper anterior half of the symphysis remodeled; in males, the incisors maintained their horizontal position as the labial sulcus developed. PMID- 1416241 TI - Long-term orthodontic tooth movement response to short-term force in the rat. AB - Both the amount of force applied and the duration of the application affect tooth movement. To study the effect of duration, adult male Sprague-Dawley rats were fitted with orthodontic appliances delivering a 40-gm initial mesial tipping force to the maxillary molars. The animals were divided into two longitudinal groups (I: 1 hour and II: 24 hours; N = 15). Sham-treated control (III) and 14 day (IV) continuous cross-sectional force tooth movement data were also included for comparison (72 rats per group). Extraoral cephalometric radiographs were obtained at appliance placement and at 1, 3, 5, 7, 10, & 14 days. Tooth movement was determined with respect to palatal implants. ANOVA indicated significant differences existed over time in each group (p = 0.0001). Continuous force applied for 14 days generated a classic three-part tooth movement curve. Short term forces were characterized by initial mesial movement, a distal relapse period (d3-d5), and a late mesial movement period (d7-d14). The results suggest short-term forces of 1 and 24 hours initiate remodeling events, which result in tooth movement 7 to 14 days later and that the minimum effective duration of a 40 gm activation is less than 1 hour in this animal model. PMID- 1416242 TI - Comparison of mandibular growth with other variables during puberty. AB - The purpose of this investigation was to compare growth characteristics of the mandible during puberty with growth characteristics of the hyoid bone, cervical vertebrae, hand bones and standing height. Data were compiled from serial lateral cephalometric roentgenograms, hand-wrist roentgenograms and body height records of 33 Japanese girls between 9 and 14 years old. Records were updated annually. The mandibular growth rate differed from the other growth rates. The timing of maximum growth velocity of the mandible varied more widely than the timing of maximum growth velocity of the other parameters measured, and the total amount of mandibular growth did not correlate to any other measurement. The timing and magnitude of circumpubertal growth acceleration of various components of the body vary within a certain range of difference. However, the amount and timing of mandibular growth seems to be more variable than the other areas studied. PMID- 1416244 TI - Computer assisted orthognathic surgical treatment planning: a case report. PMID- 1416243 TI - A functional rationale for routine maxillary bonded retention. AB - A technique is presented for the lingual bonded retention of anterior teeth. Functional concepts to guide the goals of orthodontic treatment during finishing are reviewed. The importance of proper anterior guidance is emphasized as the protector of posterior teeth in eccentric jaw position. Clinical procedures for attaining optimum function are suggested, including the elimination of removable retainers. PMID- 1416245 TI - Orthodontics with a tender touch. PMID- 1416246 TI - Molecular cloning and sequence analysis of a chicken ornithine decarboxylase cDNA. AB - A chicken embryo cDNA library was screened with a mouse probe for ornithine decarboxylase (ODC) and 14 positively hybridizing clones isolated. The longest of these (1.7 kb) was sub-cloned and sequenced. It is estimated that the clone comprises approximately 98% of the coding region for chicken ODC. The DNA sequence shows 78% identity with the human ODC cDNA sequence and the deduced amino acid sequence is almost 90% homologous to mouse and human. Both the peptide and cDNA sequences show interesting potential regulatory features which are discussed here. PMID- 1416247 TI - Genetic linkage analysis between protein polymorphisms and the FecB major gene in sheep. AB - A genetically linked marker locus is sought for the Booroola gene (FecB), a major gene which confers increased prolificacy in sheep. We examined 18 polymorphic proteins in sheep and found 10 to be informative in half-sib families where the Booroola gene was segregating. Recombination was observed between each of the protein loci and the Booroola gene. The loci and exclusion distance for each (calculated as the recombination fraction where the lod score was equal to -2.0) are as follows: NADH diaphorase, DIA1 (9.2 cM); arylesterase, EsA (11.9 cM); haemoglobin beta chain, HBB (17.5 cM); leucine amino peptidase, LAP (19.7 cM); malic enzyme, ME1 (14.8 cM); ovine plasminogen antigen, OPA (12.6 cM); alpha-1 protease inhibitor, PI2 (5.7 cM), erythrocyte 'X' protein, Prot-X (25.3 cM); post transferrin, PTF (2.2 cM); transferrin, TF (33.8 cM). PMID- 1416248 TI - Temperature gradient gel electrophoresis: detection of a single base substitution in the cattle beta-lactoglobulin gene. AB - An A in equilibrium with G transition in exon III is known to differentiate alleles A and B of the cattle beta-lactoglobulin (BLG) gene. A BLG exon III fragment containing the transition site was amplified by the polymerase chain reaction. Temperature gradient gel electrophoresis (TGGE) was then used to detect this transition and hence to genotype cattle: the AT base-pair in allele A was readily distinguished from the GC base-pair of allele B. TGGE can be used to detect any single base-pair substitution, and thus is a powerful method of detecting genetic variability. PMID- 1416249 TI - Characterization of a porcine variable number tandem repeat sequence specific for the glucosephosphate isomerase locus. AB - A variable number of tandem repeat from a porcine glucosephosphate isomerase intron has been isolated and sequenced. The repeat has a unit size of 39 bp, is highly conserved and is present in at least 14 copies. Flanking sequences show a sequence periodicity of 53-54 bp and some sequence homology to the 39 bp repeat. A considerable part of the genomic DNA has been lost during subcloning and is considered to be deletion prone or refractory to propagation in E. coli. The tandem repeat is locus specific and detects at least six alleles in BamHI digested porcine DNA. No homology to other tandem repeat sequences has been found. PMID- 1416250 TI - Characterization of swine short interspersed repetitive sequences. AB - Swine genomic DNA segments containing repetitive sequences were isolated from a porcine genomic library using genomic DNA as a probe. Three fragments containing the repetitive sequences from two of the primary phage clones were subcloned for sequence analysis, which revealed six new PRE-1 repetitive families other than those reported earlier by Singer et al. (Nucleic Acids Research 15, 2780, 1987). The frequency of the repetitive sequences in the swine genome was estimated at 2 x 10(6) per diploid genome. Sequence analysis revealed similarities between these repetitive sequences and that of arginine-tRNA gene. PMID- 1416251 TI - Genetic polymorphism of erythrocyte diaphorase in red deer, Cervus elaphus L. AB - NADH diaphorase polymorphism was identified in red deer erythrocyte lysates using starch gel electrophoresis and activity staining. The inheritance of the polymorphism was consistent with predictions of autosomal codominant inheritance of two alleles DIA1F and DIAS. In New Zealand's four main feral red deer populations (n = 188) the DIA1F allele frequency ranged from 0.491 to 0.985. A sample of North American wapiti (n = 42) was monomorphic for the DIA1F allele. PMID- 1416252 TI - A new transferrin allele in Australian goats. AB - Subdivision of TF B into two variants, B1 (faster) and B2 (slower) in Australian goat breeds was accomplished by high voltage, thin layer polyacrylamide gel electrophoresis at pH 7.9. The genes controlling the caprine transferrins were shown to be autosomal codominant alleles, TFA, TFB1, TFB2 and TFC and in the various breeds of goats, the alleles were in Hardy-Weinberg equilibrium. TFA was the most common allele in the Australian and Texan Angora, Cashmere and Dairy breeds with gene frequencies ranging from 0.652 to 0.977. TFB1 and TFB2 occurred in all four breeds while TFC was only observed in very low frequencies in Australian Angora and Cashmere breeds. PMID- 1416253 TI - Genetic polymorphism of plasma vitamin D-binding protein (GC) in Australian goats. AB - Polymorphism at the GC locus in goats was detected using isoelectric focusing (pH 4.5-5.4) and immunoblotting with antiserum to human GC. Three variants, designated A, B and C in order of decreasing mobility to the anode, were detected and were shown to be controlled by three codominant alleles, GCA, GCB and GCC. GCA and GCB occurred in all four breeds (Australian and Texan Angora, Cashmere and Dairy) with GCA being the most common and having gene frequencies ranging from 0.851 to 0.993. GCC was found only in Australian Angora and Cashmere animals. The products of the three GC alleles had isoelectric points in the range pH 4.63-4.95 and M(r) of approximately 54,375. The major isoforms of the three alleles were shown to contain sialic acid. Linkage between the GC and albumin loci was unable to be demonstrated due to the low frequency of ALBA (0.02) in the Cashmere breed. PMID- 1416254 TI - Bovine and ovine DNA microsatellites from the EMBL and GENBANK databases. AB - Bovine and ovine microsatellite sequences were extracted from the EMBL and GENBANK databases. When analysed for number of alleles and degree of heterozygosity in the CSIRO cattle reference families, allele numbers range from 1 to 14 with heterozygosities, in the polymorphic systems ranging from 15.8% to 100%. Six (46%) of the 13 bovine systems tested gave specific and polymorphic products in sheep. Similarly 2 of the 4 ovine systems gave specific and polymorphic products in cattle. These data define 11 bovine and 8 ovine microsatellite systems which are associated with known genes and are thus useful for comparative mapping studies. PMID- 1416256 TI - Polymorphism in exon 2 of the bovine lymphocyte antigen (BoLA)-DYA gene. PMID- 1416255 TI - Mouse monoclonal antibodies to swine blood group antigens. AB - Eight mouse hybridomas with haemagglutination capacity to swine blood group antigens were obtained, three of them producing antibodies capable of being used as blood group reagents. Two detected the Ba factor and another the Fa factor. The others gave non-specific and weak reactions or cross-reaction with antigens present in more than one system. We conclude that mouse monoclonal antibodies are also suitable for use in swine as a complement of polyclonal reagents. PMID- 1416257 TI - Mononucleotide repeat polymorphism at the MYHE locus in chicken. PMID- 1416258 TI - Dinucleotide polymorphism at the bovine beta-globin locus (HBB). PMID- 1416259 TI - Cat allergy. PMID- 1416260 TI - Antihistamines--is there anything safe to prescribe? PMID- 1416261 TI - The value of the Joint Council of Allergy and Immunology. PMID- 1416262 TI - Psychiatric complications of pediatric asthma. AB - Asthma is the most common chronic illness of childhood. An increased prevalence of psychopathology has been shown repeatedly to occur in severely asthmatic children, but little evidence exists to suggest that this is true for children with mild asthma. A major problem in interpreting the psychological literature addressing asthma has been the absence of studies of children with specified subtypes of the disease and the analysis of heterogeneous samples including children with a wide range of ages and poorly defined disease characteristics. Depression and anxiety disorders occur at a greater prevalence in severely asthmatic children and may be exacerbated by antiasthmatic medications. Vocal cord dysfunction may be misdiagnosed as asthma and is suggested to be associated with an increased risk of psychiatric disturbance. The presence of depressive illness in very severe asthmatic patients is associated with greater asthma mortality and requires intervention. Treatment considerations include the need for a high level of suspicion for noncompliance in patients who are nonresponsive to antiasthmatic medications, judicious use of antidepressant medication, referral of children with co-occurring psychiatric symptoms for psychiatric assessment and management, and consideration of early intervention strategies to minimize the initial expression of asthmatic symptoms. PMID- 1416263 TI - Recurrent acute urticaria in an adolescent. PMID- 1416264 TI - Asthma as a child. Symptom-free as an adult? AB - Of 123 individuals hospitalized as children (aged 5-15 years) because of asthma over a 10-year period (1953-1962), four are dead of whom three died of asthma at follow-up 23-31 years later. Using a survey questionnaire, 64 (53%) of the 117 responders (response rate 98%) claimed to be completely symptom-free. The rest were still suffering from their disease. Of the 31 symptom-free individuals still living in the community, two had decreased lung volumes and seven had positive methacholine provocation tests at re-examination, thus indicating hyperreactivity. Twenty-five individuals showed both positive skin prick tests and Phadiatop allergy tests. Nineteen individuals were suffering from allergic rhinoconjunctivitis. So, of symptom-free adults hospitalized for asthma in childhood, nearly a quarter (23%) had hyperreactive airways. The occurrence of positive skin prick test/Phadiotop and rhinoconjunctivitis was, however, even higher (80% and 61% respectively), thereby indicating that the disappearance of allergy may not be a prerequisite for restoration to health in asthma. PMID- 1416265 TI - Bronchial inflammation in mite-sensitive asthmatic subjects after 5 years of specific immunotherapy. AB - We examined the pattern and degree of the inflammatory process in bronchial biopsy specimens taken by fiberoptic bronchoscopy in eight asthmatic subjects (two women aged 19-38 years) after 5 years of specific immunotherapy (SIT) to mite extracts (SIT group). At the time of study, they received a maintenance dose of mite-extracts (last subcutaneous administration 3 weeks before bronchoscopy). Results were compared with those found in eight matched mite-sensitive subjects with stable asthma (two women aged 19-36 years; non-SIT group) and in eight healthy individuals (four women aged 22-29 years; control group). Bronchial biopsy specimens were fixed in periodate-lysine-paraformaldehyde, embedded in glycol methacrylate, and stained with hematoxylin-eosin and 2% toluidine blue. Number of eosinophils, mast cells, and total nucleated cells were counted separately in the epithelium and lamina propria by light microscopy and expressed as cells/high power field. Within the epithelium, eosinophil and mast cell counts in SIT and non-SIT groups were significantly higher compared to controls, whereas total cell counts were not statistically different. Within the lamina propria, total cell count in SIT and non-SIT groups was significantly higher compared with the control group, whereas mast cells were similar. The number of eosinophils in both SIT and non-SIT groups was higher compared with controls; however this reached statistical significance only in SIT-groups. Comparison between the two groups of asthmatics did not show any significant difference for any cell counts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416266 TI - Budesonide in grass pollen rhinitis. AB - To determine the relative efficacy, to compare the incidence of adverse experiences, and to assess the systemic glucocorticoid effect of nasal preparations of budesonide, 200 micrograms bid, and placebo, 50 adult patients with seasonal allergic rhinitis due to grass pollen were studied in a stratified, double-blind parallel group design. After a 2-week baseline period, budesonide nasal spray, 100 microgram per nostril twice a day, was compared with placebo nasal spray over a 4-week treatment period. Supplementary treatment with chlorpheniramine, 4-mg tablets, was permitted when necessary to control symptoms. Daily symptom and medication diaries were kept by the patients. Investigator assessments of symptoms and side effects were made at clinic visits at 2-week intervals. At baseline and again towards the end of the study, blood samples were drawn for the determination of plasma cortisol levels and 24-hour urine samples collected for the measurement of 17-hydroxycorticosteroid output. Of the 24 men and 26 women entering, 49 completed the study. Symptom scores for sneezing, stuffy nose, and nasal secretion all decreased dramatically from baseline when budesonide treatment was started. The decrease in symptoms was greater for budesonide than for placebo (P < .001). There was no difference between budesonide and placebo with regard to eye itch and rescue medication used. Morning nasal washes were taken during the grass season before treatment was started and 16 to 17 days after. They showed a significant decrease in TAME esterase levels in secretions in the budesonide treated patients (P = .03) but not in the placebo-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416267 TI - Mustard allergy. Two anaphylactic reactions to ingestion of mustard sauce. AB - Two cases of anaphylactic reactions set off by the ingestion of a small amount of mustard sauce are described. Mediation by specific IgE to mustard was determined by skin prick tests and radioimmunoassay, which suggested a type I hypersensitivity mechanism. Despite the antigenic potency of mustard, a spice that is consumed frequently, very few cases of hypersensitivity from ingestion have been described. PMID- 1416268 TI - Fel d I allergen: skin and or saliva? AB - To determine the relative importance of saliva and sebaceous glands as sources of Fel d I allergen, we compared Fel d I levels at the base and tip of the hair in areas presenting more or less sebaceous glands and areas licked more or less frequently. The amount of Fel d I was significantly higher at the base than the tip of the hair. Further, it was strongly correlated with the density of sebaceous glands. This study demonstrated that the most abundant source of Fel d I allergen is cat skin. PMID- 1416269 TI - Diagnosis and "desensitization" in tetanus vaccine hypersensitivity. AB - A 5-year-old boy was evaluated for a history of an anaphylactic reaction to a DPT immunization at 18 months of age. Cutaneous tests and RAST disclosed high titers of IgE antibody to tetanus toxoid vaccine. Variable sensitivity to different vaccine commercial preparations was demonstrated. Immunization was achieved using a 9-step graded dosing schedule with the tetanus toxoid vaccine to which the patient was least sensitive. PMID- 1416270 TI - The progress of allergy and immunology, 1942-1992. PMID- 1416271 TI - [Comparative study of conventional spinal anesthesia and combined spinal-epidural anesthesia in gynecological surgery]. AB - A prospective study was carried out to compare the qualities of spinal block with those of combined spinal-epidural anaesthesia (CSEA). It included 63 patients, ranked ASA 1 or 2, aged between 35 and 75 years, scheduled for gynaecological surgery due to last more than 2 hours, and randomly allocated to two groups. In the first group (n = 34), spinal anaesthesia was carried out with the patients sitting, in the L3-4 interspace, using 15 mg of hyperbaric bupivacaine with 0.4 mg of adrenaline. In the second group (n = 29), a catheter was inserted in the epidural space through the L2-3 interspace, and spinal anaesthesia carried out as in the first group, using bupivacaine without adrenaline. Once the highest level of analgesia had been reached, aliquots of 0.5% plain bupivacaine were injected through the epidural catheter, until anaesthesia of T5 was obtained. In the spinal group, general anaesthesia was required in 3 cases, as anaesthesia only reached the T12 level in 2 cases, and as surgery lasted longer than the spinal in the third one. In the CSEA group, excellent analgesia was obtained in all patients. Sensory blockade lasted 308 +/- 48 min at the T12 level, versus 162 +/- 51 min in the spinal group (p < 0.025), and 361 +/- 51 min at the L2 level, versus 210 < 44 min in the other group (p < 0.025). "Topping up" was possible with the epidural catheter only, thus raising the level of sensory blockade, making it deeper, and increasing its duration. It avoids the use of general anaesthesia in case of failed spinal blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416272 TI - [Etomidate modifies hemodynamic response to fentanyl in patients with impaired left ventricular function]. AB - The haemodynamic effects and the side-effects of anaesthesia using high doses of fentanyl were compared in two groups of 12 patients each. All the patients had poor left ventricular function and were scheduled for elective coronary artery bypass graft surgery or valvular replacement. Patients were randomly assigned to either group. In group EF, patients were given 5 micrograms.kg-1 of fentanyl, followed by 0.3 mg.kg-1 of etomidate. Once they had lost consciousness, they were given 15 mg of pancuronium and 25 micrograms.kg-1 of fentanyl over a 5 min period. Patients in group F received the full 30 micrograms.kg-1 dose of fentanyl over a 5 min period, followed by 15 mg of pancuronium. The patients were intubated 2 min after the end of the fentanyl infusion. They were mechanically ventilated with 100% oxygen. Anaesthesia was maintained with a continuous infusion of fentanyl (total dose 100 micrograms.kg-1). The usual haemodynamic parameters were monitored and calculated, as well as pain during injection of the drugs, myoclonia, chest wall rigidity and the time to loss of consciousness. The two groups were comparable with respect to age, weight, height and surgery. One third of the patients in group EF complained of pain during etomidate injection. The time required to loose consciousness was shorter in group EF (55 +/- 16 sec) than in group F (177 +/- 56 sec) (p < 0.001). The cardiac index decrease in group EF (2.0 +/- 0.4 l.min-1.m-2 vs. 1.9 +/- 0.4 l.min-1.m-2) (p < 0.05), respectively between the time just before tracheal intubation (T1), and 10 min after tracheal intubation (T3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416273 TI - [Hemodynamic effects of bathing in severe burnt patients]. AB - Repeated water immersion is currently used in France in the treatment of severe burn injury. A prospective study was carried out to assess the haemodynamic effects of immersing such patients in a half sitting position in water, the temperature of which was kept at 35 degrees C. The burn exceeded 50% of body surface area (BSA), with at least 30% being third degree burns. The study was carried out during the first bath, three days after the injury. The patients were immersed up to the clavicles. They were sedated with 2 mg.h-1 of both flunitrazepam and phenoperidine, and were mechanically ventilated. The following haemodynamic parameters were monitored: heart rate, arterial blood pressure (the transducer being level with the arterial catheter), right atrial and pulmonary arterial pressures (the transducer being level with the right atrium, level which had been marked on the chest before immersion and placed two intercostal spaces higher after immersion because of the change in position of the heart). The cardiac output was measured using the thermodilution method. The patient's temperature was monitored with the thermistance of the Swan-Ganz catheter. Values were obtained before immersion, after 15 and 30 minutes of immersion, and 5 minutes after the end of the bath. Nine patients were included, 2 women and 7 men, aged between 24 and 45 years, weighing 73.7 kg on average. Burn size was 78% of BSA (range 64 to 95%). Water immersion was maintained for 34 +/- 3 min. The right atrial, mean pulmonary arterial, and wedge pressures, and the cardiac and systolic indices increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416274 TI - [Value of transcranial Doppler ultrasonography in patients with suspected brain death]. AB - Transcranial Doppler ultrasonography (TCD) is a non invasive technique which assesses blood flow velocitics in basal cerebral arteries. Specific patterns have been observed in brain death. In a continuous series of 72 patients, the TCD recordings from the intracranial internal carotid and middle cerebral arteries were compared with the results from the usual investigations for brain death, such as electroencephalogramme (EEG), and arteriography. All the patients were clinically brain dead: Glasgow score of 3, apnoea, bilateral mydriasis, loss of cortical function and cerebral reflexes. This clinical diagnosis was confirmed by and isoelectric EEG with or without angiographic circulatory arrest. Two characteristic patterns were identified: an oscillating to and fro signal, with a positive sharp systolic peak and a negative diastolic reflux; and a systolic peak without any diastolic component. The absence of signal on both sides did not allow any conclusion, except when this pattern occurred during follow-up. The oscillating pattern was seen on both sides in 60 patients (83%), and, in 3 other patients, only on one side, always combined with a contralateral systolic peak pattern, in 3 other patients. A bilateral systolic peak pattern was identified in 7 patients (10%). The TCD results were compared with angiography in 37 cases. TCD circulatory arrest preceded angiographic arrest by six hours in three cases. Hypotension was the main limitation to this technique. n the other hand, TCD may be used in patients treated with sedative drugs. The non invasive character of TCD, its low cost, the possibility of repeating it at the patient's bedside make TCD a very interesting diagnostic tool.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416275 TI - [Monitoring of intracranial pressure with intraparenchymal fiberoptic transducer. Technical aspects and clinical reliability]. AB - A fiberoptic intracranial pressure transducer (Camino) was assessed prospectively in 100 patients. In all, 122 sensors were inserted intraparenchymally at the bedside, without the help of a neurosurgeon. Before the procedure, patients were given 2 to 4 mg of phenoperidine. The scalp was opened over a few millimeters in the frontal paramedian area. A burr holc was made with a 2 mm bit. The dura mater was opened and a hollow screw inserted in the diploe. When the zero of the transducer had been obtained, a 5 cm length was inserted within the screw. The transducer was then about 5 mm deep within cerebral parenchyma. The procedure took an average of about 15 min. An intracerebral haematoma around the transducer occurred five times. One had to be drained surgically. There were no infectious complications. The daily baseline drift was about 0.3 mmHg. The system seemed to be reliable: there was close agreement between the intracranial pressure (ICP), neurological status and CT scan findings. In trauma cases, there was also good correlation between mean ICP and the basal cistern obliteration score, finally, ICP became equivalent to mean arterial blood pressure in all brain dead patients. It is concluded that this system may be used in all cases where ICP requires to be monitored, even when the lateral ventricles are no longer visible, or when craniotomy has been performed. This will most probably result in a more extended use of ICP monitoring in neurosurgical intensive care. PMID- 1416276 TI - [Influence of sampling techniques on blood sodium, potassium and hemoglobin concentration measured by a blood gas analyser]. AB - A study was carried out to assess the influence of sampling technique on sodium, potassium and haemoglobin blood concentrations measured simultaneously with a bedside blood gas analyser (Ciba Corning 288) and in the central laboratory. Blood samples from forty intensive care unit patients were used to test cight techniques: capillary tubes (Radiometer & Corning), preheparinized syringes (Terumo 2.5 ml, Sherwood 1 and 3 ml, Corning 1 ml) and Radiometer 2 ml) and a conventional syringe (Plastimed) which was rinsed with heparin just before use. Each result was compared with that obtained by the laboratory. For haemoglobin concentrations, the results were underestimated by the bedside analyser with Terumo, Corning, Radiometer and Plastimed syringes. The differences between results varied with the haemoglobin concentration, and precision was low: 38 to 55% of results showed a difference of more than 1 g.dl-1, and 13 to 25% a difference of more than 2 g.dl-1. The results obtained with the capillary tubes and the preheparinized syringes (Sherwood) showed differences independent of the value, as well as higher precision: 13 to 20% of values differed more than 1 g.dl 1, and 0 to 3% more than 2 g.dl-1. The capillary tubes moderately overestimated the haemoglobin concentration (+0.02 to +0.65 g.dl-1) while Sherwood's syringes underestimated it (-0.48 to -0.94 g.dl-1). For the sodium and potassium concentrations, the eight methods gave results similar to those obtained by the laboratory. It is concluded that these modules for bedside biological analysis, when used in optimal conditions, rapidly provide reliable results for some parameters. PMID- 1416278 TI - [Electromagnetic location of central venous catheters]. AB - A new technique, the Cath Finder (Pharmacia Deltec) system, for locating central venous catheters is described. It was initially designed to facilitate the insertion of the PAS Port (Pharmacia Deltec), a long central venous catheter with an implantable chamber. It is based on a low intensity high frequency electromagnetic field generated by a locator wand. A preconnected sensor guide wire is introduced into the catheter so as to make the catheter tip detectable by the electromagnetic field. The wand is placed over an appropriate landmark on the anterior chest wall (third right rib, parasternally). When the centre of the field has been passed over by the sensor tip in the catheter-sensor assembly, a light signal is set off. This technique is simple and easily mastered. It is far less cumbersome than the usual techniques, like fluoroscopy and chest X-rays. The Cath Finder provides reliable continuous information on the position of the catheter tip during its insertion. It seems to provide an acceptable alternative to peroperative fluoroscopy. The accuracy of this system was assessed in ten patients. All had malignancies and required long term central venous access. In 6 cases, catheterisation and locating of the catheter were uneventful. In 2 cases, the catheter entered a wrong vein. The diagnosis having been made with the Cath Finder system, the false route was amended and the catheter placed accurately. In one case, the sensor in the catheter broke.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416277 TI - [Continuous venovenous hemofiltration after cardiac surgery. A retrospective study in 16 patients with multiple organ failure]. AB - As intermittent haemodialysis in critically ill patients is often associated with circulatory instability and hypotension, pumped continuous veno-venous haemofiltration (CVVH) has been proposed as an alternative. This technique was used postoperatively in 16 cardiac surgery patients with cardiogenic shock (cardiac index < 2.2 l.min-1.m-2), anuria and multiple organ failure. A mean haemofiltration rate of 0.5 to 1 l.h-1 was used. Average length of treatment was 57 +/- 38 h. Two patients were improved and weaned from CVVH after 96 and 144 h respectively. The other fourteen died. A mean 200 +/- 50 ml of liquid were removed every hour. The technique was well tolerated by the cardiovascular system. The systolic arterial pressure, heart rate and cardiac index remained unchanged. Body weight had decreased by 3 +/- 1 kg after 48 h of use. Similarly, serum creatinine concentration was lowered from 337 +/- 32 mmol.l-1 to 252 +/- 27 mmol.l-1 (p < 0.001). At that time, urea and creatinine clearances were 18 +/- 2 ml.min-1, and 15 +/- 1 ml.min-1 respectively. After 24 h of CVVH, both serum sodium and potassium concentrations had been decreased, from 148 +/- 3 mmol.l-1 to 142 +/- 2 mmol.l-1 (p < 0.001), and from 5.7 +/- 0.3 to 4.2 +/- 0.15 mmol.l-1 (p < 0.001) respectively. In addition, pH increased significantly from 7.13 +/- 0.1 to 7.30 +/- 0.04 (p < 0.001). These results were comparable with these of other authors regarding safety and efficiency of CVVH. The low patient survival rate (12.5%) was due to the severity of cardiac impairment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416279 TI - [Anesthetic consequences of hemodynamic effects of angiotensin converting enzyme inhibitors]. AB - Angiotensin converting enzyme inhibitors (ACEI) are used increasingly to treat cardiovascular diseases, and so, therefore, the number of patients scheduled for surgery and treated preoperatively with these drugs. Haemodynamic instability has sometimes been observed during anaesthesia in these patients, leading some authors to discontinue ACEI administration before anaesthesia. However, recent physiological data concerning the renin angiotensin system (RAS) and ACEI pharmacological data may increase our understanding of the mechanisms of cardiovascular interaction between ACEI and anaesthesia. The RAS is involved in blood pressure regulation when extracellular fluid volume is decreased and in case of hypovolaemia, by inducing vasoconstriction and longterm volume regulation. Arterial vasoconstriction is the target for ACEI. However, venoconstriction may maintain venous return and cardiac output in spite of reduced blood volume. On the other hand, ACEI treatment impedes cardiac adaptation to acute changes in extracellular fluid volume. This effect may be increased by underlying pathology (especially in hypertension) as well as by anaesthesia. A combination of an increased sensitivity to acute changes in ventricular load due to treatment with ACEI and anaesthesia in hypertensive patients or in patients with cardiac failure may carry a high risk of hypotension. Specific studies on haemodynamic tolerance of anaesthesia in patients chronically treated with ACEI are required to assess the prevalence of this risk and how to manage it. PMID- 1416280 TI - [The role of the bacteriological laboratory in the criteria for choosing and monitoring antibiotic treatment]. AB - The constant development of clinical bacteriology and the consequence this has on the way an infected patient is approached and treated require that be examined a bacteriology laboratory's contribution in choosing and monitoring an antibiotic treatment. In the economic context of hospitals, one of the aims is to rationalize the prescription of biological investigations, as well as that of antibiotic treatments. The patient's history, his clinical state as well as the place where he has been admitted must be taken into account to establish, together with microbiologists, a hierarchy of the biological investigations required and to adapt the antibiotic treatment. In the laboratory, both the bacteriostatic and bactericidal sensitivity to antibiotics may be assessed in vitro. The best therapeutic antibiotic concentrations may be obtained by monitoring the pharmacokinetics of antibiotics. PMID- 1416281 TI - [Embolism in the brain stem as a consequence of cervical spine dislocation complicated by thrombosis of the vertebral artery]. AB - A case is reported of a 52-year-old man who sustained a cervical spine dislocation in a road traffic accident, which was complicated by an initially asymptomatic vertebral arterial thrombosis. Embolism from this thrombosis into the vertebrobasilar territory during the surgical manoeuvers to reduce the dislocation was the cause of a fatal postanaesthetic coma. Such unexpected but life-threatening neurological consequences may be found with trauma of the cervical spine of various intensities. The diagnosis may be made by angiography. However, the usefulness of atraumatic investigations, such as the cervical doppler, and the indications for angiography need to be assessed. PMID- 1416282 TI - [Postoperative re-expansion causing unilateral pulmonary edema]. AB - A case of re-expansion pulmonary oedema is reported. A 7-year-old girl, after having been operated on for a lung tumour, had a postoperative haemothorax combined with atelectasis of the left upper lobe. After she had recovered from the first dose of chemotherapy, the thoracotomy wound was reopened to remove the partially organised and lysed haemothorax, as well as the very thickened pleura. The patient developed clinical signs of pulmonary oedema very shortly after the end of the anaesthetic (tachypnoea, cyanosis, a decrease in oxygen saturation when FIO2 < 1, pink frothy secretions in the endotracheal tube). End-inspiratory crepitations became audible in the left lung field only. The chest film showed left-sided diffuse nodular alveolar opacities. The girl was again ventilated, with + 5 cmH2O positive end-expiratory pressure. She was extubated 36 h later, and discharged a few days later without any sequela. This case was the first to be described in a child after pleural surgery. The death rate, estimated from a literature survey, is about 20%. PMID- 1416283 TI - [Persistent leakage of cerebrospinal fluid after removal of a device implanted for subarachnoid analgesia]. AB - A case is reported of a persisting leakage of cerebrospinal fluid (CSF) occurring after removal of a subarachnoid analgesia kit. The kit had been inserted in a 79 year-old man who had severe perineal cancer pain. Fifteen months later, after a second episode of meningitis, the kit was removed. The leakage was noticed a few hours after removal of the kit. Biological parameters confirmed the fluid was most certainly CSF. Despite making the patient lie prone, water restriction and a compressive dressing, the leakage was still present three days later. A blood patch, and the epidural injection of biological glue, were of no avail. The leakage was only stopped by tying off the fistula with a ligature. The actiology and treatment of skin CSF fistulae after puncture of the dura mater are discussed. PMID- 1416284 TI - [Hypomagnesemia associated with hypocalcemia after undetected parathyroidectomy]. AB - A case is reported of hypomagnesaemia and hypocalcaemia occurring postoperatively in a 59-year-old man operated on for hypopharyngeal carcinoma which had extended to the upper extremity of the oesophagus. Surgery consisted in total pharyngolaryngectomy, ganglion curage, jejunal transplant, thyroidectomy and tracheostomy. Total parathyroidectomy was not mentioned in the surgical report. Hypocalcaemia was first noticed on the day following the procedure. On the tenth postoperative day, the patient became agitated and had myoclonia and muscle fasciculations. Nystagmus and orthostatic hypotension also occurred. There were no cardiac signs. Treatment with calcium alone was insufficient. These symptoms only disappeared once magnesium sulphate had been added. PMID- 1416285 TI - [The good use of Diprivan (propofol)]. PMID- 1416286 TI - [Postoperative death of a patient with a giant meningioma]. PMID- 1416287 TI - An application of computational fluid mechanics to the air flow in an infant incubator. AB - An application of the computational fluid mechanical method to the air flow in a two-dimensional model of an infant incubator was described. The air flow in a numerical model was simulated and the Navier-Stokes equations were directly solved using a finite-volume method incorporating a body-fitted coordinate system on a mini-supercomputer. The model was based on a real infant incubator, slightly simplified for the sake of computing speed, and included a model of a baby. The number of computation grids was 101 x 61 = 6161. The calculation was carried out under the condition of unsteady, starting airflow and the results were examined by the means of color graphics animation. There were several very large scale eddies in the incubator free space, and their global structure did not show strong changes once they were established. Although the global structure did not change, small scale eddies were shown to be produced around the air inlet and convected down through the free space of the incubator. From these results, we believe that assuming steady and uniform flow in the incubator may not always be relevant when considering heat loss of a baby in an incubator. The steady and uniform flow has been previously assumed either implicitly or explicitly by most of the authors. PMID- 1416288 TI - Influence of low dissolved oxygen concentration in body fluid on corrosion fatigue behaviors of implant metals. AB - In their previous study, the authors carried out a fatigue test for AISI 316, 316L stainless steels and COP1 alloy in a living animal body and observed a remarkable deterioration in the fatigue durability of these metals. In that study, it was concluded that the reason the corrosion resistance of the metals was reduced in the living body was that the low concentration of dissolved oxygen gas in the body fluid (the partial pressure pO2; 28-78 mmHg) was insufficient to form the chromium oxide passivation film on the metal surface, and the base metal (iron) was released into the environmental fluid in ionic form. In this paper, with the concentration of dissolved oxygen gas in a physiological normal saline solution being set equivalent to that of living body fluid, fatigue tests on AISI 316 were made to simulate the stress corrosion behavior of the metal in the living body. As a result, remarkable deterioration of fatigue strength was observed in the low O2 concentrated normal saline solution, which was the same as that in the living animal body. PMID- 1416290 TI - A microcomputer oxygen control system for ventilatory therapy. AB - A computer-based feedback system has been developed to adjust the concentration of oxygen in the inspired gas of a patient under artificial respiration. The system uses a proportional plus integral controller and feedback of arterial oxygen saturation to adjust the inspired oxygen fraction. The effectiveness of the controller has been tested using a dynamic, mathematical model of the human respiratory system. This relatively sophisticated model has been developed and examined in the past, and it has been shown that it can realistically describe the human respiratory system for a wide variety of test conditions. The performance of the oxygen control system has been evaluated using the simulation model. The response of the controller to different disturbances is always stable, with arterial pressure of oxygen returning to normal in less than 12 minutes. Some of the simulation results are presented to illustrate the dynamic behavior and robustness of the controller. PMID- 1416289 TI - Hoffmann half-frame external fixation rigidity and its relationship to universal joint slippage. AB - Hoffmann half-frame external fixation device configurations often fail under minimal loads secondary to joint slippage. In these experiments improved universal joints that were developed in an earlier study were tested on Hoffmann half-frame assemblies. The rigidity of selected half-frame configurations was tested in four modes (axial compression, torsion, medial-lateral and anterior posterior four-point bending). These results were compared to those of an earlier, similar study looking at the standard Hoffmann half-frame. No changes in overall rigidity were noted, but significant increases in yield loads and loads to frame failure were achieved. Such improvements will increase the reliability and usefulness of the Hoffmann device to the orthopaedic community. PMID- 1416291 TI - Descriptive ventilatory mechanics from noninvasive analog display of ribcage and abdominal flow. AB - A rapidly responding analog display of ventilatory flow at the mouth, ribcage and abdomen allows interpretation of the relative activity of the diaphragm, accessory inspiratory muscles and abdominal expiratory muscles. These relative movements are exaggerated by having volunteers perform the ventilatory maneuvers of sniff, rapid exhalation and cough. Activity and regional lung flow can change in time periods in the tens of milliseconds. These rapid (within an inspiratory or expiratory time) relational changes in respiratory muscle activity and regional lung flow have not previously been demonstrated with a simple noninvasive measurement. PMID- 1416292 TI - A population-based, multivariate analysis of the association between 911 access and per-capita county trauma death rates. AB - STUDY OBJECTIVE: Decreased response times for injury should decrease the morbidity and mortality of trauma. The 911 telephone access is designed to improve the response time for emergencies. The purpose of this study was to analyze the association between county 911 access and per-capita county trauma death rates. METHODS: Data on all trauma deaths from 1986 through 1988 were obtained from the North Carolina Medical Examiner's data base. Counties were divided into those that had 911 access during the entire study period (15), those that never had 911 access (62), and those that installed 911 during 1987 (ten). Counties obtaining 911 access in 1986 or 1988 were excluded (13). RESULTS: The per-capita trauma death rate in counties that had 911 access throughout the study was 4.3 +/- 0.8 versus 5.0 +/- 1.1 per 10,000 population in counties that never had 911 access (P less than .01). Compared with counties with 911 access, counties without 911 were more rural, were less likely to have a trauma center, and were less likely to have advanced life support certification (P less than .03 for all). Controlling for these other factors, multivariate analysis demonstrated that 911 access had no significant independent association with per-capita county trauma death rates. In the ten counties that implemented 911 access in 1987, no significant change occurred in per-capita county trauma death rates after implementation of 911. CONCLUSION: Although counties with 911 access had lower trauma death rates by t-test, multivariate analysis showed no significant independent association of 911 access with per-capita county trauma death rates. In the ten counties that implemented 911 access in 1987, no significant changes in trauma death rates occurred after implementation. Although other factors may explain these findings, this study showed no significant independent impact of 911 access on per-capita county trauma death rates. PMID- 1416293 TI - Survival after out-of-hospital cardiac arrest in elderly patients. Belgian Cerebral Resuscitation Study Group. AB - STUDY OBJECTIVES: To study whether age of the cardiac arrest patient is related to prognostic factors and survival. STUDY DESIGN: Retrospective analysis of a prospective registration of cardiac arrest events in the mobile ICUs of seven participating hospitals. STUDY POPULATION: Two thousand seven hundred seventy-six out-of-hospital cardiac arrests in which advanced life support was initiated. Cardiac arrests with a precipitating event requiring specific therapeutic consequences and with specific prognosis were not included in the analysis (eg, trauma, exsanguination, drowning, sudden infant death syndrome). RESULTS: Neither resuscitation rate (23%) nor mortality caused by a neurologic reason (9%) was significantly different between age groups. Mortality after CPR of non-neurologic etiology was significantly higher in the elderly patient (younger than 40 years, 16%; 40 to 69 years, 19%; 70 to 79 years, 30%; 80 years or older, 34%; P less than .005) and had a negative effect on survival in resuscitated elderly patients (P less than .05). Elderly patients more frequently had a dependent lifestyle before the arrest (P less than .025), an arrest of cardiac origin (P less than .001), electromechanical dissociation as the type of cardiac arrest (P less than .025), and a shorter duration of advanced life support in unsuccessful resuscitation attempts (r = -.178, P less than .0001). CONCLUSION: Because survival two weeks after CPR was not significantly different between age groups, we suggest that decision making in CPR should not be based on age but on factors with better predictive power for outcome and quality of survival. PMID- 1416295 TI - Comparison of two new immobilization collars. AB - STUDY OBJECTIVE: To evaluate the limitation of movement of four cervical collars, with emphasis on two new extrication collars. DESIGN: Ranges of motion permitted by four extrication collars, measured by two goniometric techniques, were compared. Times required to apply each collar were noted and compared. SETTING: In a laboratory setting, volunteers were asked to flex, extend, laterally bend, and rotate their necks, first without restriction and then with each of the collars applied. TYPE OF PARTICIPANTS: Participants were healthy volunteers who worked either in the Department of Physical Therapy or in the Emergency Department of Tulane Medical Center Hospital. INTERVENTIONS: The collars used were the Nec-Loc Extrication Collar, Philadelphia Collar, Philadelphia Red EM Collar with Immobilizer, and Vacuum Splint Cervical Collar. MEASUREMENTS: Measurements were performed first using the head goniometer and then the hand held goniometer. Time required for application was measured in seconds. Statistical evaluation was performed using repeated measure analysis of variance and then Newman-Keuls multiple comparison procedure. MAIN RESULTS: The Vacuum Splint Cervical Collar restricted range of motion of the cervical spine most effectively. CONCLUSION: A cervical collar with design characteristics similar to the Vacuum Splint Cervical Collar (ie, a rigid collar that incorporates part of the thorax) will restrict movement of the neck more effectively than shorter, less rigid collars. PMID- 1416294 TI - Emergency cervical-spine immobilization. AB - STUDY OBJECTIVE: To determine the effectiveness of a cervical-spine immobilization using a rigid cervical extrication collar and an Ammerman halo orthosis with and without spine boards. DESIGN: A mixed model multivariate design with one within factor (device type) and one between factor (spine board application). SETTING: Radiology suite. TYPE OF PARTICIPANTS: Twenty normal men with a mean age of 29.6. INTERVENTIONS: Unrestrained cervical motion was compared with motion in a cervical extrication collar and an Ammerman halo orthosis with and without a spine board. MEASUREMENTS: Photographic measurement of head and neck motion during maximal flexion-extension, lateral bending, and rotation. Radiologic measurement of maximal intervertebral flexion-extension. MAIN RESULTS: Both cervical extrication collar and Ammerman halo orthosis significantly reduced motion in all planes (P less than .001) with the Ammerman halo orthosis reducing these motions significantly more (P less than .001). With the use of a spine board these motions were restricted even more (P less than .001). The Ammerman halo orthosis with a spine board provided the greatest immobilization, equivalent to that provided by an halo-vest. CONCLUSION: A rigid cervical collar and a spine board provide significantly better immobilization than the collar alone. Further immobilization is provided by an Ammerman halo orthosis. PMID- 1416296 TI - Circadian variation in the time of request for helicopter transport of cardiac patients. AB - STUDY OBJECTIVES: The literature has demonstrated circadian rhythms in the occurrence of nonfatal myocardial infarction, ischemia, and sudden death. We hypothesized that requests for helicopter transport of acutely ill cardiac patients followed a similar circadian pattern and differed significantly from requests for helicopter transport of other categories of patients. DESIGN: Prospective study of requests for helicopter transport of 1,128 consecutive air medically transported patients over a 24-month period. SETTING: One tertiary-care teaching hospital. MEASUREMENTS AND MAIN RESULTS: The periodic structure of the time distribution of cardiac requests for helicopter transport was examined with a two-harmonic regression analysis using a 24-hour period of oscillation. Seven hundred eighty-seven cardiac and 315 noncardiac patients could be evaluated. The times of requests for helicopter transport were tabulated into hourly intervals. Cardiac-related requests for helicopter transport were significantly different from noncardiac-related requests for helicopter transports (P less than .009 by Wilcoxon rank sum test, P less than .032 by Kolmogorov-Smirnov test). The regression model for cardiac requests for helicopter transport was also significant (P less than .0001, R2 = .81) with increasing requests for helicopter transport from 6:00 AM until 12:00 noon. CONCLUSION: The time distribution of requests for helicopter transport for cardiac patients demonstrates a striking circadian variation not observed in noncardiac patients. This observation strengthens mechanistic inferences from studies of circadian variation and suggests a "morning-loaded" staffing pattern for air medical services predominantly transporting cardiac patients. PMID- 1416297 TI - Using regression analysis to predict emergency patient volume at the Indianapolis 500 mile race. AB - BACKGROUND: Emergency physicians often plan and provide on-site medical care for mass gatherings. Most of the mass gathering literature is descriptive. Only a few studies have looked at factors such as crowd size, event characteristics, or weather in predicting numbers and types of patients at mass gatherings. PURPOSE: We used regression analysis to relate patient volume on Race Day at the Indianapolis Motor Speedway to weather conditions and race characteristics. METHODS: Race Day weather data for the years 1983 to 1989 were obtained from the National Oceanic and Atmospheric Administration. Data regarding patients treated on 1983 to 1989 Race Days were obtained from the facility hospital (Hannah Emergency Medical Center) data base. Regression analysis was performed using weather factors and race characteristics as independent variables and number of patients seen as the dependent variable. Data from 1990 were used to test the validity of the model. RESULTS: There was a significant relationship between dew point (which is calculated from temperature and humidity) and patient load (P less than .01). Dew point, however, failed to predict patient load during the 1990 race. No relationships could be established between humidity, sunshine, wind, or race characteristics and number of patients. CONCLUSION: Although higher dew point was associated with higher patient load during the 1983 to 1989 races, dew point was a poor predictor of patient load during the 1990 race. Regression analysis may be useful in identifying relationships between event characteristics and patient load but is probably inadequate to explain the complexities of crowd behavior and too simplified to use as a prediction tool. PMID- 1416298 TI - Demographics of emergency medical care at the Indianapolis 500 mile race (1983 1990). AB - BACKGROUND: The Indianapolis 500 Mile Race, the largest single-day, single-venue sporting event in the world, is attended by an estimated 400,000 people. Major illness and injury are treated at the Hanna Emergency Medical Center, the track hospital. Minor illness is treated at ten outlying aid stations. PURPOSE: We describe the demographics of emergency medical care at the Hanna Emergency Medical Center. DESIGN: Descriptive. METHODS: Patient care data for patients treated at the medical center are first recorded on paper charts and then coded and transferred to computer. Data regarding patients treated at the medical center during eight consecutive races (1983-1990) were analyzed. Frequency of treatment and medical cardiac arrest rates were calculated. Aid station data and medical center records from nonrace days were not analyzed. RESULTS: The average number of patients treated per year at the track hospital was 139. The total number treated over the eight-year period was 1,113, yielding a frequency of treatment of 0.35 per 1,000. Analysis showed 16.2% of the proprietary treatment codes involved intoxication; 15.4%, lacerations (other than feet); 11.0%, pre existing conditions; and 8.5%, heat illness. During the eight years, there were four medical cardiac arrests (incidence of 0.0125 per 10,000 spectators), all resulting in death. A fifth spectator died after being struck by a wheel from a race car. There were no driver deaths on race day. CONCLUSION: Descriptive data regarding medical care of crowds may be useful to emergency specialists who must staff, order supplies, and plan treatment facilities for similar mass gatherings. It is evident from this and other mass-gathering studies that there is a need for consistency in nomenclature and data collection. This will allow more accurate comparisons of emergency medical care between venues. PMID- 1416299 TI - Level of uncompensated care delivered by emergency physicians in Florida. AB - STUDY OBJECTIVES: To determine selected characteristics of patients who present for care in emergency departments in Florida, the proportion who appear to be uninsured or underinsured, and the magnitude of uncompensated care provided by the emergency physicians in selected EDs in Florida. DESIGN: Retrospective analysis of billing data. SETTING: Twenty-five EDs in Florida. MAIN RESULTS: Uninsured patients comprised 20.6% of the sample. Emergency and urgent patients were 39.9% of the sample. The overall collection ratio was 59.2%. CONCLUSION: Emergency physicians provide substantial amounts of uncompensated care. PMID- 1416300 TI - Hospital delays and problems with thrombolytic administration in patients receiving thrombolytic therapy: a multicenter prospective assessment. Virginia Thrombolytic Study Group. AB - STUDY OBJECTIVES: To assess the timing of key decisions and clinical events in the treatment of acute myocardial infarction with thrombolytic therapy. DESIGN: Prospective study of emergency department patients. SETTING: EDs in 11 urban and two rural hospitals. TYPES OF PARTICIPANTS: Patients with presumed acute myocardial infarction for whom a decision was made in the ED to administer thrombolytic therapy. MEASUREMENTS AND MAIN RESULTS: Statistical analyses included determination of frequency of response, cross tabulation analysis, and Wilcoxon rank sum tests. In 210 thrombolytic-treated patients (mean age, 57 +/- 14.1 years), a median time of 155 minutes elapsed between pain onset and therapy; 67% of the delay was pre-ED arrival. The median time between ED arrival and the initial ECG was six minutes. The median time required for physicians to make a treatment decision was 20 minutes, followed by another median time of 20 minutes for staff to begin drug infusion. The median total hospital (door-to-needle) time was 50 minutes. Significantly shorter delays occurred in urban, teaching, and high-volume hospitals; when thrombolytics were stocked and/or started in the ED; and when emergency physicians treated without involving private attending physicians. Although 95% of patients received tissue plasminogen activator, six patients treated with anisoylated plasminogen-streptokinase activator complex experienced a significantly faster door-to-needle time (P less than .05). CONCLUSION: Thrombolytics should be stocked and started in the ED. Emergency physicians should generally make the decision to administer thrombolytic therapy with reference to accepted protocols without awaiting an ED consultation from either private attendings or cardiologists. PMID- 1416301 TI - Spontaneous pneumomediastinum: clinical and natural history. AB - STUDY OBJECTIVE: To evaluate the clinical characteristics and natural history of patients presenting with spontaneous pneumomediastinum. DESIGN: A retrospective case series was conducted to identify patients diagnosed with spontaneous pneumomediastinum. ICD-9 discharge codes were used for 1984 to 1990 at two institutions, and emergency department records of a third hospital were reviewed for 1981 to 1986. Clinical features, interventions, complications, setting, etiology, symptoms, and length of hospital stay were recorded. SETTING: Three university tertiary care hospitals. PARTICIPANTS: All ED patients more than 12 years old with a diagnosis of spontaneous pneumomediastinum. INTERVENTIONS: None. RESULTS: Seventeen cases were identified. Age range was 15 to 41 years (mean, 25 years). Presenting symptoms were chest pain in eight (47%), dyspnea in three (18%), both symptoms in three (18%), and neither in three (18%). Three patients complained only of throat discomfort. Nine (52%) had a Hamman's crunch, 11 (65%) had subcutaneous emphysema, and two (11%) had a small pneumothorax. Five (29%) were smokers, and five (29%) had normal esophograms. Thirteen of 17 (76%) cases were associated with illicit inhalation drug use. Twelve cases (70%) had history of a "Valsalva-type" maneuver. All but three were admitted to a hospital, with a mean stay of 2.5 days (range, one to six). No patient suffered complications or required interventions for spontaneous pneumomediastinum. Specifically, no patient developed a subsequent pneumothorax or airway compromise. The three patients not admitted were followed up by telephone contact. All did well with rapid resolution of their symptoms. CONCLUSION: Most spontaneous pneumomediastinum cases occur in the setting of inhalational drug use. One hundred percent of patients will have a symptom directly related to the spontaneous pneumomediastinum, with 82% presenting with either dyspnea or chest pain. Most (88%) will present with either subcutaneous emphysema or a Hamman's crunch on examination. Simple spontaneous pneumomediastinum has a very benign course and does not require hospitalization. Serial radiographs, likewise, did not change the medical management of spontaneous pneumomediastinum. PMID- 1416302 TI - The 1989 Loma Prieta earthquake: impact on hospital patient care. AB - STUDY OBJECTIVE: To provide an overview of the Loma Prieta earthquake regarding patient care in affected hospitals. DESIGN: A retrospective review of medical records using International Classification of Disease, ninth revision (ICD-9) codes and a personal interview questionnaire. SETTING: Fifty-one hospitals in the six-county area most affected by the earthquake. TYPE OF PARTICIPANTS: Patients seeking care in emergency departments of study hospitals and supervising emergency physicians and ED nurses at the time of the earthquake. MEASUREMENTS: ED census data, complaint and diagnosis, disposition, and operative procedures for patients seen during the study period. MAIN RESULTS: Affected hospitals experienced a 15% increase in ED census during the study period. Minor trauma was the most common patient complaint. Open wound (870-897), contusion (920-924), and fracture (800-829) were the most common ICD-9 diagnostic categories. The percentage of patients presenting to EDs during the study period who were hospitalized increased slightly compared with baseline. Seventy-five percent of operative procedures were earthquake related; 63.7% of these were for fracture reduction. Physicians and nurses had somewhat conflicting opinions on adequacy of ED staffing. A small number of emergency physicians had difficulty in obtaining diagnostic tests on the night of the earthquake. Physicians noted no differences in diagnosis or treatment resulting from the earthquake. CONCLUSION: The Loma Prieta earthquake resulted in minimal negative impact on patient care in hospitals in the study area. The use of the ICD-9 classification deserves further consideration and study to improve the predictive value of disaster illness and injury reporting. The event has provided the stimulus for Bay Area hospitals to further improve plans for patient care during a disaster. PMID- 1416303 TI - Injuries and deaths from gang violence: they are preventable. PMID- 1416304 TI - Day-night differences are not always due to circadian control. PMID- 1416305 TI - Universal access: its potential impact on emergency medicine. AB - The nation's current economic conditions, the first time in 60 years that a recession has adversely affected the middle class, might well be the actual trigger mechanism in the passage of a US universal access plan. When enacted, it would provide emergency medicine and other basic physician and hospital benefits to the currently uninsured patients now seen in hospital EDs, in doctors' offices, and as inpatients. It will, thereby, enhance current physician-patient relationships and enable many of the working poor and their dependents to receive medical care. Conventional widsom suggests that such a social insurance plan could significantly reduce the number of routine visits to hospital EDs, assuming that additional, accessible, and high-quality alternative primary-care services are developed. In any case, a universal access plan should improve the percentage of billed charges collected by emergency physicians. The nation's 1,500 third party payers, with their managed care strategy, will have difficulty (for the reasons outlined) in micromanaging such external pressures as ensuring high quality patient care, more benefits (including tertiary services), and less cost to the private and public sectors. As there is more micromanaging by third-party payers to reduce expenditures, it will be increasingly difficult for emergency physicians to find specialists willing to accept previously uninsured patients, except at public or teaching environments where the delivery of services to uncompensated patients has been the pattern for several decades.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416306 TI - Public policy and the emergency department. PMID- 1416307 TI - The effectiveness of 911. PMID- 1416308 TI - The avoidable delay. PMID- 1416309 TI - The Canadian health care system. AB - Canadians have enjoyed a close and harmonious relationship with Americans for more than a century. We have learned and benefited greatly from our close association. We are pleased to share our experiences with the United States in the same spirit of mutual respect and support that has characterized our close relationship and opened our borders. PMID- 1416310 TI - A rational approach to shift work in emergency medicine. AB - As the only medical specialists who routinely provide continuous 24-hour daily coverage, emergency physicians are all too familiar with the demands of shift work. Although shift work has a pervasive effect on the practice of emergency medicine and is regarded as a major stressor, it has received little attention per se in our literature and in our residency training programs. We review the principles of circadian rhythms and their effects on sleep and alertness, and recommend ways by which emergency physicians can better schedule themselves to mitigate the negative consequences of working shifts. PMID- 1416311 TI - Ethical conflicts in the prehospital setting. AB - STUDY OBJECTIVE: To assess the range of ethical conflicts that confront prehospital care providers. DESIGN: Convenience sample, from October 1989 to January 1990. SETTING: An urban advanced life support emergency medical service that transports approximately 3,000 patients per month. METHODS: Six hundred seven paramedic responses were analyzed by a single observer. An ethical conflict was identified when the paramedic faced a dilemma about what "ought to be done" and the paramedic's values conflicted or potentially conflicted with the patient's. Cases with potential ethical consequence were brought to experts in medical ethics and epidemiology for further analysis and classification. RESULTS: Ethical conflicts arose in 14.4% of paramedic responses (88 of 607 cases). Twenty seven percent of the conflicts involved issues of informed consent, such as refusal of treatment or transport, conflicts of hospital destination, treatment of minors, and consent for research. Difficulties regarding the duty of the paramedics, usually under threatening circumstances, accounted for 19% of the dilemmas encountered. Requests for limitation of resuscitation accounted for 14%. Other circumstances that presented ethical conflicts involved questions of patient competence (17%), resource allocation (10%), confidentiality (8%), truth telling (3%), and training (1%). CONCLUSION: The data demonstrate a range of ethical conflicts in the prehospital setting and point to areas in which policy needs to be developed. The data also can be used in a prehospital ethics curriculum for paramedics and physicians. Because case sampling was not strictly random, absolute conclusions should not be drawn regarding the frequency of the dilemmas. PMID- 1416313 TI - Ethical aspects of resuscitation. PMID- 1416312 TI - Pressure on the emergency department: the expanding right to medical care. AB - Lack of a comprehensive health care system in the United States has resulted in a series of legal cases that have expanded the common-law right to care in the hospital emergency department, thereby bringing increased pressure on hospitals to provide care under an ever-widening variety of nonemergency conditions. Health care legislation at the state and federal level during the 1980s expanded the concept of physician duty to include women in labor as well as any condition that could reasonably be expected to lead to serious impairment to bodily functions or serious dysfunction of any bodily organ or part. Presently, any patient presenting to a hospital ED must be examined to determine whether an emergency exists. The expanding definition of an emergency and mandated patient examination requirements have hit urban hospitals particularly hard, as the uninsured and disenfranchised increasingly find the ED their only source of medical care. The United States needs a national health care solution that does not rely on the ED as the locus of care for general medical practice. Failure to act will jeopardize the ability of hospital EDs to provide the highly specialized care that only they can provide and will put more hospitals at financial risk as they struggle to comply with state and federal law while serving a growing population of uninsured and underinsured patients. PMID- 1416314 TI - Ethical issues of resuscitation. American College of Emergency Physicians. PMID- 1416315 TI - Inappropriate electrical countershocks by an automated external defibrillator. AB - A 79-year-old man who was in normal sinus rhythm with a palpable pulse was inappropriately shocked twice by a fully automated external defibrillator. The second shock resulted in ventricular tachycardia. The device then countershocked a third time, restoring normal sinus rhythm. The problem occurred primarily because the rescuers did not follow the device's instructions warning against applying the device in analysis mode to a patient with a palpable pulse, and they attempted to analyze the rhythm in a moving vehicle. Motion artifact and T waves that were relatively tall compared with the QRS amplitude were misinterpreted as ventricular fibrillation by the device. This example of inappropriate countershocks delivered by rescuers using a fully automated device illustrates the importance of proper training and continuing education. PMID- 1416316 TI - Out-of-hospital pleomorphic ventricular tachycardia and resuscitation: association with acute myocardial ischemia and infarction. AB - Pleomorphic ventricular tachycardia is characterized by QRS complexes with repeated variation in polarity, amplitude, and regularity. When associated with prolongation of the QT interval, the term torsades de pointes is used to describe the arrhythmia. It usually is seen clinically in association with class IA antiarrhythmic drugs such as quinidine and procainamide, bradycardia, hypokalemia, and, much less often, other drugs and electrolyte disorders as well as a result of congenital and neurogenic causes. It also may accompany acute myocardial infarction or ischemia. We describe four patients in whom pleomorphic ventricular tachycardia was observed as the presenting rhythm or during the course of resuscitation in out-of-hospital cardiac arrest. In all four patients, acute myocardial ischemia appeared to be the provocative mechanism. Therapeutic implications include an awareness of the unusual behavior of this arrhythmia, especially its propensity to terminate spontaneously. Such awareness may prevent the delivery of unnecessary defibrillatory shocks. PMID- 1416317 TI - Is the cervical spine clear? Undetected cervical fractures diagnosed only at autopsy. AB - Undetected cervical-spine injuries are a nemesis to both trauma surgeons and emergency physicians. Radiographic protocols have been developed to avoid missing cervical-spine fractures but are not fail-safe. Three case reports of occult cervical fractures documented at autopsy in the face of normal cervical-spine radiographs and computerized tomography scans are presented. PMID- 1416318 TI - Minimizing gang violence in the emergency department. AB - Street gang members are frequently injured, and the violence of their subculture may follow them from the streets into the emergency department. We present four cases in which in-hospital gang violence occurred or was prevented. To decrease the risk of injury from gang-related violence within the hospital, we offer guidelines for patient care and health care provider safety. Emphasis is on education, awareness, and early hospital security involvement. PMID- 1416319 TI - Open and closed peritoneal lavage. PMID- 1416320 TI - Use of methohexital in the ED. PMID- 1416321 TI - Tympanic thermometer accuracy. PMID- 1416322 TI - Effects of isopropyl alcohol, ethanol, and polyethylene glycol/industrial methylated spirits in the treatment of acute phenol burns. AB - STUDY OBJECTIVE: To compare the effects of water rinse with those of isopropyl alcohol, polyethylene glycol with industrial methylated spirits, or ethanol on cutaneous phenol burns. DESIGN: Controlled trial with all animals receiving all treatments applied to different cutaneous phenol burn sites. TYPE OF PARTICIPANTS: Swine weighing 9 to 18 kg. INTERVENTIONS: In phase 1, each burn site was treated with water rinse for zero, one, or five minutes combined with either isopropyl alcohol, polyethylene glycol with industrial methylated spirits, ethanol, or no other treatment. Biopsies of treatment sites were done at 30 minutes and at 48 hours. In phase 2, a pilot study, the effect of isopropyl alcohol, polyethylene glycol with industrial methylated spirits, or water treatment on serum phenol levels was noted in animals with 5%, 10%, and 15% body surface area burns. MEASUREMENTS AND MAIN RESULTS: In phase 1, on histological examination of biopsy specimens, significant differences in tissue damage occurred among the groups (P < .05). Isopropyl alcohol and polyethylene glycol with industrial methylated spirits were the most efficacious treatments; the duration of water rinse had no significant effect. In phase 2, the systemic absorption of phenol may be greater with water treatment than with isopropyl alcohol treatment. CONCLUSION: Isopropyl alcohol and polyethylene glycol with industrial methylated spirits are equally effective in the amelioration of phenol burns of less than 5% total surface area. The wider availability of isopropyl alcohol makes it potentially the most useful treatment for these small burns. Further studies of its risks are needed. PMID- 1416323 TI - Lithium absorption prevented by sodium polystyrene sulfonate in volunteers. AB - STUDY OBJECTIVE: To determine if sodium polystyrene sulfonate prevents absorption of lithium in human beings. DESIGN: Prospective, crossover study. TYPE OF PARTICIPANTS: Healthy volunteers age 22 to 34 years (three women and three men). INTERVENTIONS: After an eight-hour fast, subjects ingested 0.5 mEq/kg (18.5 mg/kg) lithium carbonate. One hour later, they ingested either 857 mg/kg sodium polystyrene sulfonate in 4 mL water/g sodium polystyrene sulfonate (experimental) or an equal volume of water without sodium polystyrene sulfonate (control). MEASUREMENTS AND MAIN RESULTS: Serum lithium levels were drawn zero, one, two, three, four, six, eight, ten, 12, and 24 hours after lithium ingestion. The sodium polystyrene sulfonate group had a smaller mean area under the serum concentration curve (11.6 +/- 1.0 mEq/L.hr versus 13.6 +/- 1.5 mEq/L.hr, P < .001) and lower mean highest measured lithium level (0.85 +/- 0.11 mEq/L versus 1.05 +/- 0.10 mEq/L, P < .05) compared with the control group. There was no significant difference in 24-hour urine lithium excretion or in serum sodium and potassium levels. CONCLUSION: Sodium polystyrene sulfonate administration decreased absorption of lithium after a lithium carbonate overdose. Sodium polystyrene sulfonate may be useful clinically for gastric decontamination after lithium overdoses. PMID- 1416324 TI - Effect of sodium polystyrene sulfonate on lithium bioavailability. AB - STUDY OBJECTIVE: To examine the effect of a single dose of sodium polystyrene sulfonate and sorbitol on lithium absorption. DESIGN: Prospective, randomized, crossover. SETTING: University teaching hospital. TYPE OF PARTICIPANTS: Healthy volunteers. INTERVENTIONS: Subjects ingested 600 mg lithium carbonate on two occasions, with and without 30 g concomitant sodium polystyrene sulfonate. Blood samples were drawn up to 24 hours after ingestion and assayed for serum lithium concentration. MEASUREMENTS AND MAIN RESULTS: Compared with control, sodium polystyrene sulfonate and sorbitol reduced the area under the lithium serum concentration-time curve by 11.33%, reduced the mean observed peak serum lithium concentration 0.07 +/- 0.08 mmol/L, and delayed the time to the mean observed peak serum lithium concentration by 2.04 +/- 2.40 hours. CONCLUSION: Sodium polystyrene sulfonate and sorbitol may be used in patients immediately or shortly after ingestion of a significant acute overdose of lithium in situations in which hemodialysis cannot be instituted promptly. PMID- 1416325 TI - Whole-bowel irrigation as adjunctive treatment for sustained-release theophylline overdose. AB - STUDY OBJECTIVE: To determine a therapeutic benefit for whole-bowel irrigation (with polyethylene glycol-electrolyte lavage solution) as adjunctive treatment to multiple doses of activated charcoal following an overdose of sustained-release theophylline. DESIGN: Randomized crossover study. Three treatment arms were separated by one-week intervals. SETTING: Animal care facility housing. TYPE OF PARTICIPANTS: Eight female mongrel dogs. INTERVENTIONS: Unanesthetized dogs were given approximately 75 mg/kg of sustained-release theophylline. In treatment arm 1, 1 g/kg activated charcoal was administered by nasogastric tube at two hours after ingestion followed by 0.5-g/kg doses at five and eight hours. During treatment arm 2, beginning two hours after theophylline ingestion, 25 mL/kg whole bowel irrigation solution was administered every 45 minutes for four doses followed by activated charcoal. In treatment arm 3, the first dose of activated charcoal was given ten minutes before beginning the whole-bowel irrigation protocol. MEASUREMENTS AND MAIN RESULTS: Serum theophylline levels were measured at zero, two, four, five, eight, 12, 16, and 24 hours after ingestion. Mean serum theophylline levels, area under the curve (P = .13), and terminal half-lives (P = .69) for each treatment group were not statistically different. This negative study had an 81% power to detect a 50% reduction in the area under the curve by whole-bowel irrigation treatment. CONCLUSION: In this model, whole-bowel irrigation did not add to the therapeutic benefits of activated charcoal. PMID- 1416326 TI - Cocaine liberation from body packets in an in vitro model. AB - STUDY OBJECTIVE: To quantitatively assess cocaine liberation from various body packet materials. DESIGN: 100-milligram cocaine packets (plastic bags with various wrapping techniques, paper, and condoms) were placed in a simulated gastric medium. Samples were also tested in an alkalinized gastric medium, with determination of both cocaine and benzoylecogonine concentrations using high performance liquid chromatography with ultraviolet detection. RESULTS: Cocaine liberation was greatest in acid medium, with increasing liberation from condom packets to cellophane bags (three wrapping techniques used) to paper packets. The same trend was noted in alkaline medium but with a far lower maximum cocaine concentration accompanied by rapid hydrolysis to its inactive metabolite, benzoylecgonine. CONCLUSION: Cocaine liberation of a known quantity of drug is dependent on the wrapping method and material used; thus, a good history from the "body-stuffer" is essential to predict potential cocaine liberation and toxicity. Rapid hydrolysis of cocaine to its inactive metabolite in an alkaline medium implies a role for gastric alkalinization in the acute management of these patients. PMID- 1416327 TI - Is admission after intravenous heroin overdose necessary? AB - STUDY OBJECTIVES: To investigate the time of onset and incidence of complications in patients presenting to the emergency department with an IV heroin overdose and the need for routine admission of such patients. METHODS: A retrospective chart review of hospital and emergency medical service records of 124 patient visits involving IV heroin overdose over a five-month period. We also reviewed the death certificates of 115 persons having succumbed to a narcotic overdose over a 44 month period and compared these with our hospital records. SETTING: Urban county hospital. TYPE OF PARTICIPANTS: Patients presenting to the ED with an IV heroin overdose. RESULTS: There were five deaths in the ED, 12 hospital admissions, and 107 patients who were discharged home. Neither delayed onset of pulmonary edema nor recurrence of respiratory depression was observed. Of the 115 persons having succumbed to a narcotic overdose, eight had been seen previously at our hospital for a heroin overdose. There is no evidence that any of these eight deaths would have been prevented by a 24-hour hospital observation period. CONCLUSION: Complications arising from an IV overdose of heroin are usually evident on arrival in the ED or shortly thereafter. On retrospective review we have found no evidence that admission to the hospital and 24 hours of observation are of benefit to patients who are awake, alert, and lacking evidence of pulmonary complications after an IV heroin overdose. PMID- 1416328 TI - Prospective evaluation of adverse drug interactions in the emergency department. AB - STUDY OBJECTIVE: To determine the incidence and risk factors of clinically relevant adverse drug interactions occurring in emergency department patients. DESIGN: This report describes the drug interactions identified in an emergency population. Patients' drug regimens were evaluated prospectively at the time of the emergency evaluation. SETTING: University hospital ED. TYPE OF PARTICIPANTS: Convenience sample of 341 patients. INTERVENTIONS: Patients' medications on arrival at the ED (current medications) and medications initiated in the ED were entered into Hansten's computer-based drug interaction program to identify potential drug interactions. All potential drug interactions were brought to the attention of the attending emergency physician, whose subsequent actions were noted. Clinically relevant interactions were determined by a physician panel based on the ED attendings' actions, set criteria, and a review of hospital charts and four-week telephone follow-up of patients with potential drug interactions. MEASUREMENTS AND MAIN RESULTS: Three hundred forty patients were enrolled. One hundred thirty-five potential drug interactions were identified in 61 patients. Among these 135 potential drug interactions and 61 patients, we identified 20 clinically relevant interactions in 15 patients. The incidence of clinically relevant interactions was significantly higher (chi 2 = 3.95, P = .047) among current medication (9.7%) than medication added in the ED (3.1%). Clinically relevant interaction from both current and ED-initiated medication was associated with taking three or more medications on ED arrival (P = .016 and .045, respectively). Multiple regression showed age of 60 years or older to be the sole predictor of clinically relevant interaction among current medication (P = .05). CONCLUSION: Clinically relevant adverse drug interaction was significantly less from medication administered or prescribed in the ED than from current medication. PMID- 1416329 TI - Frequently nebulized beta-agonists for asthma: effects on serum electrolytes. AB - STUDY OBJECTIVE: To determine the magnitude of the changes in serum potassium, magnesium, and phosphate during the treatment of acute bronchospasm with repeated doses of beta-adrenergic agonists. DESIGN: Prospective study of a convenience sample of asthmatic patients. SETTING: University teaching hospital emergency department. TYPE OF PARTICIPANTS: Twenty-three patients met the inclusion criteria of age of more than 16 years; a history of asthma or chronic obstructive pulmonary disease; and an acute exacerbation. INTERVENTIONS: Baseline peak expiratory flow rate and serum potassium, magnesium, and phosphate levels were measured. Nebulized albuterol (2.5 mg) was administered every 30 minutes until the patient was discharged from the ED. Before each albuterol treatment, repeat serum levels of potassium, magnesium, and phosphate were determined. MEASUREMENTS AND MAIN RESULTS: Baseline peak expiratory flow rate averaged 188 +/- 119 L/min. Serum potassium levels decreased significantly (P = .0001 by repeated-measures analysis of variance) from 4.10 +/- 0.468 (baseline) to 3.55 +/- 0.580 mmol/L (90 minutes) and 3.45 +/- 0.683 mmol/L (180 minutes). Potassium decreased to less than 3.0 mmol/L in 22% of patients at some point during the study. Magnesium decreased from 1.64 +/- 0.133 mmol/L (baseline) to 1.48 +/- 0.184 mmol/L (90 minutes) and 1.40 +/- 0.219 mmol/L (180 minutes) (P = .0001). Phosphate levels also decreased, from 3.74 +/- 1.029 (baseline) to 2.84 +/- 0.957 mmol/L (90 minutes) and 2.55 +/- 0.715 mmol/L (180 minutes) (P = .0001). CONCLUSION: Aggressive administration of nebulized albuterol during the emergency treatment of acute bronchospasm is associated with statistically significant decreases in serum potassium, magnesium, and phosphate. The mechanism and clinical significance of these findings are unknown and warrant further study. PMID- 1416331 TI - Prospective evaluation of the scapular manipulation technique in reducing anterior shoulder dislocations. AB - STUDY OBJECTIVE: To evaluate the speed, efficacy, and safety of the scapular manipulation technique in reducing acute anterior shoulder dislocations. DESIGN: Prospective study. SETTING: Urban emergency department with an annual census of 65,000 patients. PARTICIPANTS: Forty-eight adult patients with acute anterior shoulder dislocation. INTERVENTIONS: Patients had an initial neurovascular and radiographic evaluation performed. They were sedated with IV fentanyl and midazolam. The shoulder was reduced using the scapular manipulation technique. The patient was re-evaluated for any evidence of complication. The total dose of analgesic required and time to reduction were recorded. RESULTS: The scapular manipulation technique was successful in 46 of 48 (96%) cases. The average time to reduction was 6.05 minutes, and no complications were detected. Average doses of 1.83 mg midazolam and 204 micrograms fentanyl were required for reduction. CONCLUSION: The scapular manipulation technique is a very fast, effective, safe method of reducing anterior shoulder dislocations in the ED. [Kothari RU, Dronen SC: Prospective evaluation of the scapular manipulation technique in reducing anterior shoulder dislocations. PMID- 1416330 TI - Generation of an osmolality gap-ethanol nomogram from routine laboratory data. AB - STUDY OBJECTIVES: To develop a practical procedure for producing a nomogram describing the relationship between the osmolality gap and serum ethanol concentrations that is appropriate for the formulas and analytical methodologies in use at any laboratory. DESIGN: Retrospective review of serum sodium, glucose, urea nitrogen, ethanol, and osmolality values and the use of spreadsheet software in the generation of a nomogram. SETTING: Emergency department in a university affiliated county hospital. PARTICIPANTS: Two hundred three adult patients presenting with signs of alcohol intoxication. MAIN RESULTS: When either a common criterion (gap [mosmol/kg H2O] = ethanol [mmol/L]; range, -10 to +10) or a published nomogram was used for determination of consistency of the osmolality gap with the ethanol level, large percentiles of data were classified as inconsistent. Regression analysis and the method of truncated normal distributions were used to prepare a nomogram that better represented the data collected with our formulas and analytical methodologies. CONCLUSION: Interlaboratory analytical bias and the choice of the formula used for calculated osmolality limit the utility of published formulas or nomograms for the assessment of excess osmolality gap. Any laboratory can produce their own nomogram from routine patient data using the described spreadsheet procedure, without the need for measurement of volatiles other than ethanol. PMID- 1416332 TI - Foreign body retention in glass-caused wounds. AB - STUDY OBJECTIVE: To describe patient and wound characteristics that are clinically useful in identifying wounds that were caused by glass and retained a foreign body. DESIGN: Retrospective consecutive case review. SETTING: Urban, university-affiliated teaching hospital. TYPE OF PARTICIPANTS: Four hundred thirty consecutive patients with a total of 578 evaluable wounds caused by glass during a 12-month period. MEASUREMENTS AND RESULTS: Medical records were reviewed to determine patient demographics, primary wound data (eg, location, type, description), mechanism of injury, type of glass involved, and presence of foreign body sensation. Glass was found by examination in 7% of wounds. Eight percent of 137 radiographs were positive. Wounds with the highest prevalence of retained glass were puncture wounds (P < .0005), those caused by stepping on glass or by a motor vehicle accident (P < .005), and those of the head or foot (P < .003). CONCLUSION: Characteristics of wounds most likely to retain glass were identified in this retrospective study. The presence of these factors should increase the clinician's suspicion of a retained glass foreign body. The indications for radiography for the detection of retained glass in wounds should be clarified with prospective studies. PMID- 1416333 TI - Comparison of a new pressurized saline canister versus syringe irrigation for laceration cleansing in the emergency department. AB - STUDY OBJECTIVE: Studies have documented the efficacy of normal saline irrigation in decreasing wound infection rates. Wounds traditionally are irrigated using a syringe and needle with manual injection of fluid, a time- and labor-intensive method. We compared irrigation times and infection rates for wounds cleansed with syringe irrigation versus a new, single-use canister of pressurized (8 psi) sterile normal saline. DESIGN: Prospective, randomized, controlled. SETTING: Two Level I emergency departments in tertiary care hospitals, both with emergency medicine residency programs. PARTICIPANTS: Patients with lacerations requiring closure were eligible. Exclusion criteria were wounds above the clavicle more than ten hours old, wounds below the clavicle more than six hours old, insulin dependent diabetes mellitus, or antibiotic or steroid therapy. Patients (550) were entered between August 1, 1990, and January 31, 1991. Characteristics of the two treatment groups were similar for patient age, age of the wound, size and depth of the laceration, and number of sutures. INTERVENTIONS: Lacerations were irrigated with 250 mL saline in a syringe or 220 mL saline in a pressurized canister for each 5 cm of laceration. At follow-up or suture removal, patients were evaluated for signs of wound complications (cellulitis, ascending lymphangitis, purulent discharge, or dehiscence). MAIN RESULTS: The mean irrigation time for the pressurized canister group (281) was 3.9 minutes versus 7.3 minutes in the syringe irrigation group (254) (P < .0001). The complication rate for the pressurized canister group was 5.0% compared with 3.6% for the syringe irrigation group (not significant, P = .50). Only three of the 20 total complications required antibiotics (two in the pressurized canister group, one in the syringe irrigation group). CONCLUSION: Syringe irrigation times were nearly twice as long as the pressurized canister irrigation times. Use of the pressurized canister facilitates ease of irrigation and markedly decreases the time involved in this traditionally labor-intensive activity. In addition, delivery of the saline is no longer operator dependent, ensuring generation of pressures appropriate for wound cleansing. The pressurized canisters may be useful in standardizing irrigation in wound management research. PMID- 1416334 TI - Studies involving commercial products: caveat investigator. PMID- 1416335 TI - Two crack cocaine body stuffers. PMID- 1416336 TI - An ethical foundation for health care: an emergency medicine perspective. Ethics Committee, Society for Academic Emergency Medicine. AB - 1. What is health and health care? Health is a state of physical and mental well being that facilitates the achievement of individual and societal goals. Good health over a lifetime is the comparative absence of pain and suffering, illness and disease, each of which could prevent people from pursuing their goals. Health care includes those services that provide adequate nutrition and shelter; sanitary, safe, unpolluted living and working conditions; personal medical services; and nonmedical personal and support services. The medical community can best address the area of personal medical services, which includes interventions to prevent disease, minimize morbidity from existing diseases, diagnose and cure illness, relieve pain and suffering, and provide education for the continued promotion of health. Society must also provide health care services such as adequate nutrition, shelter, and education about health care issues, including prevention that could result in reduced expenditures for curative services. 2. Is health care an ethical or legal right? At this time, there is no legal right to universal health care in the United States, although there is a patchwork of limited legislated rights to health care benefits for some citizens. Ethically, there is a right to health care; however, it is a limited right best expressed as a societal obligation to provide care rather than an open-ended individual right to receive any and all health care resources on demand. In restructuring our health care system, our society must identify the values that will serve as the foundation for our health care system. A health care system that stresses societal rather than individual priorities is essential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416337 TI - Failure of gastric emptying and charcoal administration in fatal sustained release theophylline overdose: pharmacobezoar formation. AB - We report the case of a fatal theophylline overdose from a sustained-release preparation in a 54-year-old woman. Initial serum theophylline concentration was 31.3 mg/L. Manifestations of mild toxicity cleared in the emergency department after treatment with gastric lavage, charcoal, and a cathartic. A life threatening overdose was not suspected, and the patient arrested eight hours after discharge from the ED. At autopsy, her serum theophylline concentration was 190.1 mg/L. A white, waxy mass weighing 318.8 g and containing 29 g theophylline, representing the residue of many sustained-release tablets, was found in her stomach. This case reinforces the importance of obtaining repeat serum theophylline levels in patients with sustained-release theophylline overdose. Gastric pharmacobezoar formation should be considered in cases of sustained release theophylline overdose with rising theophylline levels and patient deterioration, despite adequate gut decontamination. PMID- 1416338 TI - Portal vein gas embolism from hydrogen peroxide ingestion. AB - A 40-year-old woman who ingested a 35% hydrogen peroxide solution presented to the emergency department with abdominal pain. Acute abdominal series showed gas in the portal vein system. The patient was admitted and treated conservatively. She was released after five days in the hospital with no major sequelae. PMID- 1416339 TI - Intravenous injection of household bleach. AB - The widespread use of household bleach (5.25% sodium hypochlorite) as a disinfectant by IV drug users may cause an increase in the number of IV injections of this substance. We report the case of a 31-year-old man who injected less than 1 mL of bleach and then experienced transient left-sided chest pain and vomiting. The patient did not have any serious complications. This report is similar to the only other reported case in the medical literature of an IV injection of a small amount of bleach. Based on these two reports, household bleach appears to be safe when used as a disinfectant by IV drug users, but more studies are needed. PMID- 1416340 TI - Survival following hydrofluoric acid ingestion. AB - Systemic toxicity after significant dermal exposure to hydrofluoric acid includes rapid development of hypocalcemia and hyperkalemia, leading to ventricular fibrillation. Similar dysrhythmias have occurred in patients after ingestion of sodium fluoride-containing compounds. Ingestion of hydrofluoric acid could induce similar cardiac toxicity; however, reported cases of hydrofluoric acid ingestion rarely have been described, and the rapid death of these patients has not allowed verification of this hypothesis. On two separate occasions, a 70-year-old woman ingested up to 2 oz of a 8% hydrofluoric acid-containing solution. Recurrent ventricular fibrillation with concurrent hypocalcemia and hypomagnesemia complicated her first episode, whereas a more aggressive administration of calcium and magnesium may have prevented dysrhythmias in the second episode. Survival from ventricular fibrillation after hydrofluoric acid ingestion has not been reported previously and suggests a role for aggressive empiric calcium and magnesium replacement. PMID- 1416341 TI - Alkaline chemical keratitis: eye injury from airbags. AB - Inflation of an automobile airbag is accomplished by converting sodium azide to nitrogen gas. The bags are vented so that nitrogen and residual byproducts of combustion, such as alkaline gas, are released into the passenger compartment. We report the case of a patient who incurred a chemical keratitis after the driver's side airbag deployed. The importance of recognition and management is discussed. PMID- 1416342 TI - Torsade de pointes after inhaled pentamidine. AB - The case of a 40-year-old HIV-positive man who had multiple episodes of torsade de pointes is presented. The patient's history was pertinent for the use of inhaled pentamidine the day before admission. His episodes of torsade de pointes were refractory to the usual therapy. His presentation, laboratory work, echocardiography, computed tomography scan, and treatment are reviewed. Physicians should be aware of the association of pentamidine with torsade de pointes. PMID- 1416343 TI - Base deficit as a diagnostic test for abdominal injury. PMID- 1416344 TI - IV adenosine in the management of PSVT. PMID- 1416345 TI - Traumatic uvulitis. PMID- 1416346 TI - Invasion of enterocytes in cultured porcine small intestinal mucosal explants by Salmonella choleraesuis. AB - Porcine small intestinal explants maintained in vitro were inoculated with Salmonella choleraesuis to study the characteristics of its invasion of enterocytes. The explants were fixed at selected intervals for up to 12 hours after inoculation and examined by conventional light microscopy, immunoperoxidase staining, and transmission electron microscopy. Although there was diffuse loss of villous enterocytes during the first hour of incubation, the villi were reepithelialized by the end of 2 hours of culture, and the mucosal epithelium remained intact and appeared to be viable through 12 hours of culture. Intraepithelial S choleraesuis were not detected before 6 hours after inoculation, but after 12 hours of incubation, bacteria were numerous within enterocytes. Ultrastructurally, penetration of the brush border by S choleraesuis resulted in focal loss of microvilli. Bacteria were endocytosed into membrane bound vacuoles where most remained, but a few were free within the cytoplasm of enterocytes. Invasion of the explants closely resembled that described for live animal and cell culture models of Salmonella spp invasion. PMID- 1416347 TI - Experimentally induced infection of cats with Borrelia burgdorferi. AB - To determine whether cats could be infected experimentally with Borrelia burgdorferi, 15 cats were inoculated with approximately 1,000 B burgdorferi. Seven cats were inoculated by the IV route, 2 by the oral route, 2 by the ocular route, and 4 by the oral-ocular route. Six control cats were inoculated with phosphate-buffered saline solution by the IV, oral, and ocular routes. Prior to the start of the study, all 21 cats were seronegative for B burgdorferi on the basis of results of the indirect fluorescent antibody (IFA) test, and their blood was B burgdorferi culture negative. All of the IV, orally, and ocularly inoculated cats developed IgG antibodies to B burgdorferi as detected by IFA testing. Of 4 oral-ocularly inoculated cats, 2 developed IFA-detectable antibodies and the remaining 2 cats developed low-titer response (1:128) on postinoculation (PI) day 10 only. All control cats remained seronegative. The organism was detected in blood smears from 2 of the IV inoculated cats on PI days 10 and 24 and from 2 oral-ocularly infected cats, 1 on PI days 17 and 24 and 1 on PI day 10. Spirochetes were not detected in the blood after PI day 24. The organism was isolated from tissues of only 1 cat (the lung of an ocularly inoculated cat necropsied at 7 months after inoculation). Spirochetes were not isolated from control cats. Neither clinical signs of infection nor gross or histologic abnormalities were found in any of the inoculated or control cats. Results indicate that cats are susceptible to infection with B burgdorferi, but clinically apparent disease may not be common. PMID- 1416348 TI - Antibody response to and maternal immunity from an experimental psittacine beak and feather disease vaccine. AB - Adult umbrella cockatoos, Moluccan cockatoos, African grey parrots, and a yellow headed Amazon parrot were inoculated IM or SC with beta-propiolactone-treated psittacine beak and feather disease (PBFD) virus. Thirty- to 45-day-old African grey parrot, umbrella cockatoo, and sulphur-crested cockatoo chicks also were vaccinated with the same inoculum. The hemagglutination inhibition (HI) and agar gel diffusion tests were used to assay for post-vaccination development of anti PBFD virus antibodies. All adult vaccinates seroconverted and had increases in HI and precipitating antibodies. The vaccinated chicks had increased concentrations of HI antibodies, but precipitating antibodies could not be detected. To demonstrate that chicks from vaccinated hens are protected from PBFD virus challenge, 3 African grey parrot chicks and 2 umbrella cockatoo chicks from vaccinated hens and 1 African grey parrot chick and 1 umbrella cockatoo chick from nonvaccinated hens were exposed to purified PBFD virus. Chicks from the vaccinated hens remained clinically normal during the 50-day test period. Chicks from the nonvaccinated hens developed clinical and histologic lesions of PBFD. Infected tissues from these birds were confirmed to contain viral antigen, using immunohistochemical staining techniques. The PBFD virus was recovered from the affected birds. These findings indicate that adult and 30- to 45-day-old psittacine birds will seroconvert following vaccination with beta-propiolactone treated PBFD virus. Also, hens inoculated with beta-propiolactone-treated PBFD virus produce chicks that are, at least temporarily, resistant to virus challenge. PMID- 1416349 TI - Function of neutrophils and chemoattractant properties of fetal placental tissue during the last month of pregnancy in cows. AB - Neutrophils were isolated from the blood of pregnant cows on days 255, 265, and 275 of pregnancy, and on the day of parturition (n = 5/group), and in addition, simultaneously from 4 ovariectomized healthy cows (control animals). Neutrophils were subjected to neutrophil function assays (chemotaxis against zymosan activated serum, random migration, ingestion of 125I-iododeoxyuridine [IdUR] labeled Staphylococcus aureus, iodination of proteins, cytochrome C reduction, antibody-independent and antibody-dependent cell-mediated cytotoxicity). Results were expressed as percentage of control animals. Fetal placental tissue (cotyledon), uterine wall tissue, and skeletal muscle were obtained from the principal animals on the aforementioned days via laparotomy, and tissue suspensions were prepared. Chemotaxis of neutrophils was tested against tissue supernatants. Compared with day 255, there was an increase in ingestion of 125I IdUR-S aureus at parturition, whereas iodination of proteins and cytochrome C reduction were reduced on the day of calving. The other neutrophil functions tested did not change over time of gestation. Fetal placental and uterine wall tissue attracted neutrophils with uterine wall tissue having a tendency to be more potent than cotyledonary tissue. Skeletal muscle tissue did not attract neutrophils. There was no change in chemotaxis response of neutrophils evoked by intrauterine and uterine tissues over time of gestation. It was concluded that at parturition, neutrophil function is impaired with respect to their bactericidal effects, which may render the animal more susceptible to bacterial infections, and that the chemoattractant properties of fetal placental and uterine wall tissues are tissue-specific, at least when compared with skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416350 TI - Influence of conditioned media from bovine cotyledon tissue cultures on function of bovine neutrophils. AB - Bovine fetal placental (cotyledon) tissue obtained from pregnant cows on days 255, 265, and 275 of gestation, as well as immediately after parturition (n = 5) was incubated in media for 48 hours, and the incubation media were collected. Neutrophils from 4 ovariectomized nonpregnant cows were incubated for 2 hours with conditioned media from placental tissue cultures or medium (control). Immediately after incubation, the neutrophils were subjected to the following leukocyte function assays: chemotaxis against zymosan-activated serum, chemotaxis against undiluted conditioned media (only neutrophils that were incubated in medium only), random migration, ingestion of 125I-iododeoxyuridine Staphylococcus aureus (125I-IdUR-S aureus), iodination of proteins, cytochrome C reduction, and antibody-independent and -dependent cell-mediated cytotoxicity. Conditioned media from cultured cotyledon tissue was chemoattractant for bovine neutrophils, and increased chemotactic response of neutrophils against zymosan-activated serum by 13%. The following neutrophil functions were decreased: random migration by 25%, iodination of proteins by 44%, cytochrome C reduction by 13%, and antibody dependent cell-mediated cytotoxicity by 5%. Ingestion of 125I-IdUR-S aureus and antibody-independent cell-mediated cytotoxicity were not influenced by coincubation of neutrophils and conditioned media. Time of gestation did not alter the effects of conditioned media on neutrophil function. It was concluded that chemotactic properties of cotyledon tissue extracts, as has been reported earlier, may be attributable to substances released by fetal placental tissue. Those substances might also locally or systemically influence the oxygen dependent antimicrobial system of neutrophils, thereby causing an increased susceptibility to bacterial infections in the peripartum period. PMID- 1416351 TI - Echocardiographic evaluation of cardiac morphologic and functional variables in double-muscled calves. AB - We studied, by means of echocardiography in vivo, the cardiac consequences of the double-muscled character selection in beef cattle. Morphologic and functional echocardiographic variables were regularly estimated in 17 Friesian and 8 Belgian White and Blue calves during their growth. A total of 50 and 44 sets of data were collected in each group, respectively. Recordings were obtained, using 2 dimensional and M-mode echocardiography, and included measurements in long- and short-axis views of the heart. Most of the diastolic measurements of the left ventricle were not significantly different between breeds when normalized for body weight. To the contrary, systolic measurements of left ventricular wall thickness and dimensions were significantly (P less than or equal to 0.001) lower and greater, respectively, in Belgian White and Blue calves than in Friesian calves. This was interpreted as a result of significantly (P less than or equal to 0.001) lower left ventricular systolic functional indices in Belgian White and Blue than in Friesian calves. Echocardiographic evidence that the double-muscled selection in cattle induces alteration in morphologic variables of left ventricle was not found. However, results indicate that indices of left ventricular systolic function are lower in double-muscled calves than in calves with standard conformation. PMID- 1416352 TI - Computer-based collection and analysis of myoelectric activity of the intestine in horses. AB - Extracellular myoelectric activity from the terminal ileum, cecum, and colonic pelvic flexure was assessed in 4 adult horses. The collection and analysis of myoelectric data involved the development and use of a computer-based system. After collection, the myoelectric signal was digitally filtered to enhance the activity of interest. The smoothed signal was then processed by use of computer programs designed to identify and count spike-burst activity and estimate burst duration. The intense phases of myoelectric complexes also were identified. The propagation of myoelectric spike-burst activity was assessed over 3 electrode sites to identify the propagative patterns of intestinal motility. There was high correlation between the results of computer-based analysis and those of visual analysis. We concluded that the computer provides a fast, accurate, and reliable means of assessing myoelectric activity. PMID- 1416353 TI - Effects of general anesthesia on myoelectric activity of the intestine in horses. AB - Myoelectric activity was monitored from the terminal ileum, cecum, and colonic pelvic flexure by use of AgpAgCl bipolar electrodes in 4 adult horses before, during, and after general anesthesia. Horses were anesthetized by way of 3 commonly used regimens, including xylazine (1.1 mg/kg of body weight) and ketamine hydrochloride (2.2 mg/kg); thiopental sodium (7.7 mg/kg), followed by halothane vaporized in oxygen; and thiopental sodium (2.5 g) in guaifenesin (100 mg/ml) solution given to effect, followed by halothane in oxygen. All 3 anesthetic regimens decreased intestinal spike-burst activity in the areas monitored. The slowest return to preanesthetic myoelectric activity was observed after xylazine and ketamine administration. After both of the barbiturate/halothane anesthetic regimens, there was a rebound increase in spike burst frequency, without alteration in the proportion of propagative myoelectric events. All 3 anesthetic regimens appeared to reset the timing of the small and large intestinal migrating myoelectric complexes. By 9 hours after recovery from anesthesia, the effects of anesthesia, irrespective of regimen, had disappeared. Although anesthesia significantly (P less than 0.05) altered intestinal myoelectric activity, no particular anesthetic regimen had a prolonged effect. Results of our study indicate that the particular chosen regimen of general anesthesia is unimportant in development of motility disturbances in horses after anesthesia. PMID- 1416354 TI - Effect of xylazine on cerebrospinal fluid pressure in conscious horses. AB - Lumbosacral CSF pressure was measured in 6 horses via a catheter inserted through the lumbosacral space. Heart rate, facial artery pressure, central venous pressure, and CSF pressure were measured before IV injection of a saline solution control, for 15 minutes after saline solution injection, and for 60 minutes after the IV injection of 1.1 mg of xylazine/kg of body weight. Arterial pH and blood gases were analyzed before saline solution injection, 15 minutes after saline solution injection, and at 15, 30, and 60 minutes after xylazine injection. Constant craniocervical posture was maintained during sedation. Lumbosacral CSF pressure was significantly decreased for 15 minutes after xylazine injection. Diastolic arterial pressure was significantly increased 4 minutes after xylazine administration and diastolic and mean arterial pressure were increased at 6 and 8 minutes after xylazine administration. Small increases in systolic arterial blood pressure and central venous pressure, and a small decrease in heart rate were observed. There were no significant differences in the arterial blood gas values. It was concluded that IV injection of xylazine causes a decrease in intracranial pressure in healthy conscious horses. The effects may be different in horses with neurologic disease or cerebral trauma. PMID- 1416355 TI - Influence of cyclooxygenase inhibitors on furosemide-induced hemodynamic effects during exercise in horses. AB - Furosemide, which commonly is used as a prophylactic treatment for exercise induced pulmonary hemorrhage in horses, may mediate hemodynamic changes during exercise by altering prostaglandin metabolism. To determine if furosemide's hemodynamic effects during exercise in horses could be reversed, cyclooxygenase inhibitors were administered with furosemide. Four treatments were administered 4 hours prior to treadmill exercise at 9 and 13 m/s. They included a control treatment (10 ml of 0.9% NaCl solution, IV), furosemide (1 mg/kg of body weight, IV) administered alone, and furosemide in combination with phenylbutazone (4 mg/kg, IV, q 12 h for 2 days) or with flunixin meglumine (1.1 mg/kg, IV, on the day of experiment). Five horses were randomly assigned to complete all treatments. Physiologic variables at rest prior to exercise were not influenced by treatments. Furosemide, administered alone, reduced mean right atrial pressure and mean pulmonary artery pressure during exercise. The combinations of furosemide and flunixin meglumine or furosemide and phenylbutazone, at both levels of exercise intensity, returned mean right atrial pressure and mean pulmonary artery pressure to the value of the control treatment. During rest and exercise, plasma lactate concentration, PCV, heart rate, mean carotid artery pressure, oxygen consumption, carbon dioxide elimination, and cardiac output were not altered by any of the treatments. At 5 minutes after exercise, the administration of furosemide, alone or with phenylbutazone, reduced mean right atrial pressure. Other measured variables were not significantly influenced by treatments during recovery from exercise. These results suggested that cyclooxygenase inhibition partially reverses the decrease in mean right atrial pressure or pulmonary artery pressure induced by furosemide during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416356 TI - Kinetics of healing of grafted and nongrafted wounds on the distal portion of the forelimbs of horses. AB - Full-thickness, circular, cutaneous wounds (5 cm in diameter) were created on the distal portion of the forelimbs of 6 horses. One wound on each horse was treated with 6 full-thickness punch grafts that were obtained from the horse's neck with a 6-mm skin biopsy punch and inserted in the graft sites on day 14 after wounding. The wound on the contralateral limb was not grafted. A combination of ticarcillin disodium and clavulanate potassium was applied to the wounds when bandages were changed to control bacterial infection. Areas of each wound were measured on days 1, 7, 9, 11, 13 through 15, 17 through 22, 24, 26, 29, and 32 after wounding. Three distinguishable phases of healing were observed (expansion, contraction, and epithelialization), and the time course of each phase was evaluated, using formulas of first-order processes. Rate constants of each phase were not significantly (P less than 0.05) affected by punch grafts. PMID- 1416357 TI - Effects of split-thickness and full-thickness skin grafts on secondary graft contraction in horses. AB - Full-thickness, circular (4-cm diameter) cutaneous wounds were created on the metacarpi and metatarsi of 6 horses. Immediately after wounding, 1 wound on each horse received a meshed, split-thickness skin graft (0.64 mm) obtained from the ventrolateral aspect of the horse's thorax by use of a pneumatic dermatome, whereas a second wound received a meshed, full-thickness skin graft obtained from the pectoral area. In addition, sections of split-thickness and full-thickness grafts were refrigerated in a solution of McCoy's 5A medium, to which equine serum (10%) and gentamicin sulfate solution (16 mg/dl) were added. Ten days after wounding, 1 granulating wound on each horse was grafted with a stored, meshed, split-thickness graft, and 1 granulating wound on each horse was grafted with a stored, meshed, full-thickness graft. Areas of wounds were calculated from photographs taken of wounds on days 1, 5, 10, 15, 20, 25, and 30 after wounding. Time course of contraction was determined by use of a first-order mathematic model of changes in area through time. Rate constants of contraction for fresh or granulating wounds receiving full-thickness grafts did not differ significantly from those for fresh or granulating wounds receiving split-thickness grafts. Rate constants of contraction for grafted fresh wounds, however, were significantly less than those of grafted granulating wounds, regardless of whether a split thickness or full-thickness graft was applied. PMID- 1416358 TI - Influence of wound shape on wound contraction in horses. AB - Three sets of paired circular and square full-thickness skin wounds were made on the dorsum of the metacarpus (n = 48) of 8 horses. Each wound was 6.25 cm2 in area. The wounds were treated topically with an ointment, nonadherent dressing, and bandaged with a snug elastic wrap. Wounds were photographed every other day until healing was complete. Wound areas were measured and exponential and linear wound healing models were applied to the wound healing data generated. Wound healing variables measured for each wound were: number of days to healing, maximal size attained, rate of wound contraction (calculated by use of first order and linear models), final wound size, and percentage of wound that healed by contraction. The exponential model fit the data significantly better than the linear model. The maximal size attained by circular wounds was significantly smaller than the maximal size attained by square wounds. Wound shape did not influence the rate of wound healing. On the basis of our findings, conversion of circular defects to square defects would not speed wound healing. PMID- 1416359 TI - Fate and effect of autogenous osteochondral fragments implanted in the middle carpal joint of horses. AB - Four autogenous osteochondral fragments removed from the lateral trochlear ridge of the talus were arthroscopically placed as loose bodies in a randomly selected middle carpal joint in each of 10 horses. The contralateral middle carpal joint, subjected to a sham procedure, served as control. Postoperative treatment was consistent with that for clinical arthroscopic patients. Lameness evaluation, radiographic examination, carpal circumference measurement, and synovial fluid analysis were performed before and at scheduled intervals after surgery. After a 2-month confinement, horses were subjected to an increasing level of exercise. Horses were euthanatized at intervals through 6 months. Gross and microscopic evaluations were performed on remaining fragments, articular cartilage, and synovial membrane of each middle carpal joint. Increased joint circumference, effusion, lameness, and degenerative joint disease distinguished implanted from control joints over the 6-month period. Implanted joints were characterized by grooved, excoriated cartilage surfaces, and synovium that was thick, erythematous, and irregular. At 4 weeks, implants were found to have adhered to synovium at their subchondral bone surface. The bone within fragments was undergoing necrosis, while cartilage was preserved. At 8 weeks, fragments were radiographically inapparent, grossly evident as pale plaques on the synovial surface, and composed of dense fibrous connective tissue. Synovial membrane specimens from implanted joints had inflammatory change characterized by mononuclear cell infiltration 2 months after implantation. Physical damage was apparent within articular cartilage of implanted joints at 2 months, and was significant (P less than 0.05) at 6 months after surgery. Chondrocyte degenerative change was significant (P less than 0.05) at 6 months after surgery. Focal reduction in safranin-O uptake was observed in cartilage layers adjacent to physical defects. Osteochondral loose bodies of the size implanted in the middle carpal joint of horses in this study were resorbed by the synovium within 2 months. Synovitis and significant articular cartilage damage were associated with the implanted fragments. Regardless of origin, free osteochondral fragments within the middle carpal joint should be removed, and methods to prevent residual postoperative debris should be implemented to reduce potential for articular pathologic change. PMID- 1416360 TI - Long-term cannulation of the ovarian vein in mares. AB - A cannulation technique was developed to collect blood samples from the ovarian vein of mares over an extended period. Ovarian venous cannulae placed in 4 mares remained patent for a mean (+/- SEM) duration of 36.8 (+/- 6.2) days. During mid diestrus, concentrations of progesterone in the ovarian vein ipsilateral to the corpus luteum (1,663.8 +/- 238.8 ng/ml) were significantly (P less than 0.001) higher than concentrations measured in paired samples from the jugular vein (6.1 +/- 0.3 ng/ml). Concentration of estradiol in the ovarian vein ranged from a mean of 1,053.2 +/- 303.1 pg/ml during diestrus to 3,353.8 +/- 1,052.8 pg/ml during estrus, whereas values for 74% of samples collected concurrently from the jugular vein were near or below the sensitivity of the assay (10 pg/ml). Results of the study indicate that patent long-term ovarian vein cannulation can be achieved in mares. The cannulation technique provides access to important fundamental information on equine reproductive endocrinology, which to our knowledge, has not been available. PMID- 1416361 TI - Treatment of reperfusion injury in dogs with experimentally induced gastric dilatation-volvulus. AB - In dogs, gastric dilatation-volvulus (GDV) is characterized by cardiogenic shock, with resulting hypoperfusion. Treatment goals include reperfusion of transiently ischemic tissues, which indicates that reperfusion injury may be a factor in the physiopathogenesis of GDV. Recently, we obtained data that indicate that reperfusion injury may be involved in experimentally induced GDV. Using this GDV model, we evaluated mortality in 24 dogs of 4 equal groups, treated with deferoxamine (an iron chelator), dimethylsulfoxide (a free radical scavenger), a combination of the 2 drugs, or isotonic saline solution. All 6 dogs that were given deferoxamine survived; however, 3 dogs of the dimethylsulfoxide-treated group, 2 dogs of the combination-treated group, and 4 dogs of the saline-treated group died. Results of the study indicate that mortality associated with experimentally induced GDV is reduced by appropriate and timely pharmacologic intervention to prevent or attenuate reperfusion injury, and that deferoxamine may be more effective than dimethylsulfoxide. PMID- 1416362 TI - Evaluation of the proximal portion of the femur as an autogenous cancellous bone donor site in dogs. AB - The proximal portion of the femur was evaluated as a source of autogenous cancellous bone in dogs. Bilateral oval cortical defects were created in the lateral subtrochanteric area of the femur in 16 dogs. Cancellous bone was removed and the weight recorded. Cancellous bone was similarly harvested from the proximal portion of the humerus in 7 of these dogs. Subtrochanteric femoral defects in 11 dogs were randomly assigned to receive cancellous bone graft obtained from the femur (n = 4) or the humerus (n = 7). Subtrochanteric defects in 5 dogs were not grafted. Radiographic assessment of subtrochanteric defects was performed at 4-week intervals, and histologic assessment at 4, 8, 16, and 24 weeks after surgery. Nongrafted donor sites healed by ingrowth of trabecular bone during the first 12 weeks after surgery. By week 24, the lateral cortical wall had reformed, but remodeling was incomplete. Donor sites grafted with cancellous bone healed similarly, but with more rapid healing and more complete remodeling evident by week 24. Although the mean weight of cancellous bone harvested from the proximal portion of the femur (0.82 +/- 0.22 g) was significantly (P less than 0.05) less than that harvested from the proximal portion of the humerus (1.38 +/- 0.29 g), there was no qualitative histologic or radiographic difference in bony healing of grafted defects. We determined that the proximal portion of the femur can be safely used to provide moderate amounts of cancellous bone, and that a second bone graft can be collected from the same subtrochanteric donor site after 12 weeks. PMID- 1416363 TI - Radiographic/morphologic investigation of a radiolucent crescent within the flexor central eminence of the navicular bone in thoroughbreds. AB - The source of a previously described radiolucent crescent in the flexor cortex of the distal sesamoid (navicular) bone on the palmaro45 degrees proximal palmarodistal oblique (Pa45 degrees Pr-PaDio) clinical radiographic projection was investigated in 48 forelimb navicular bones from 24 Thoroughbreds by use of high-detail radiography and x-ray computed tomography (CT). Twenty-five of these bones also were evaluated, using microradiography and histologic examinations. Of these 25 bones, 5 had been labeled in vivo with fluorochrome markers. Tetrachrome stained 100-microns-thick nondecalcified sections of these 5 bones were examined, using epifluorescence microscopy. A reinforcement line of compacted cancellous bone, parallel and several millimeters deep to the flexor cortex in the region of the flexor central eminence, was visualized by CT in 42 of 48 navicular bones and by microradiography in 23 of 25 navicular bones investigated. Variable degrees of compaction were observed in the cancellous bone between the flexor cortex and the reinforcement line. High-detail skyline radiographic projections and reconstructed CT images indicated a crescent-shaped lucency within the flexor central eminence of the flexor cortex in the bones in which the reinforcement line was identified, but the cancellous bone between the reinforcement line and the flexor cortex had not been compacted. The radiolucent crescent seen in the flexor central eminence of the navicular bone on the Pa45 degrees Pr-PaDiO projection was not caused by the concave defect or synovial fossa of the flexor central eminence overlying the flexor cortex, as was described.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416364 TI - Comparison of standard and radionuclide methods for measurement of glomerular filtration rate and effective renal blood flow in female horses. AB - Comparison of standard and radionuclide methods for measuring glomerular filtration rate (GFR) and effective renal blood flow (ERBF) was performed in 8 healthy female horses. Inulin and p-aminohippurate solutions were administered IV as a bolus, followed by sustained administration. Urine and plasma inulin and p aminohippurate concentrations and urine volume were measured. Glomerular filtration rate and ERBF were calculated on the basis of these measurements. Glomerular filtration rate and ERBF were measured on the basis of plasma clearance of the radiopharmaceuticals, 99mTc-labeled diethylene triaminepentaacetic acid (99mTc-DTPA) and [131I]-o-iodohippuric acid (131I-OIH), respectively. Mean +/- SEM GFR, using inulin, was 1.83 +/- 0.21 ml/min/kg of body weight. Mean GFR, using 99mTc-DTPA was 1.79 +/- 0.18 ml/min/kg. Mean ERBF, using p-aminohippurate, was 15.13 +/- 1.28 ml/min/kg. Mean ERBF, using 131I-OIH, was 18.42 +/- 1.57 ml/min/kg. Analysis of variance indicated no significant difference between mean values for GFR and ERBF. Radionuclide measurement of GFR and ERBF compared well with standard methods and is an alternative technique to the cumbersome standard methods for determination of GFR and ERBF in horses. PMID- 1416365 TI - Use of end-tidal CO2 tension to predict arterial CO2 values in isoflurane anesthetized equine neonates. AB - End-tidal carbon dioxide tension (PetCO2) and arterial carbon dioxide tension (PaCO2) were determined and compared in isoflurane-anesthetized spontaneously breathing equine neonates. End-tidal carbon dioxide and PaCO2 values increased with respect to time. Difference between values of PetCO2 and PaCO2 increased over time. End-tidal carbon dioxide tension was useful to predict changes in and was more closely correlated with PaCO2 early in the anesthetic period (T less than or equal to 60 minutes). The dead space volume to tidal volume (Vd/Vt) ratio increased with respect to time, indicating increase in physiologic dead space in isoflurane-anesthetized foals. The data indicate that the increased difference between widening of the PetCO2 and PaCO2 values over time may have been attributable to hypoventilation and decreased pulmonary capillary perfusion of alveoli. PMID- 1416366 TI - Comparison of the nonionic contrast agents, iopromide and iotrolan, for positive contrast arthrography of the scapulohumeral joint in dogs. AB - Arthrographic quality and synovial inflammatory response were examined to compare the use of iopromide with that of iotrolan for arthrography of the scapulohumeral joint in 6 dogs. Radiographs obtained 1 and 3 minutes after injection of either nonionic compound were of similar quality, but radiographs obtained 5 minutes after injection of iotrolan were significantly (P less than 0.05) better than those obtained after injection of iopromide. Results of analysis of synovial fluid samples obtained at 1, 3, 7, and 14 days after injection of contrast media were not significantly different between the 2 groups. Histologic examination of synovium and articular cartilage 2 weeks after injection of iopromide or iotrolan revealed minimal inflammatory response for both contrast agents. Injection of iopromide and iotrolan into the scapulohumeral joints of dogs had less effect on synovial fluid than that reported after injection of ionic compounds. PMID- 1416367 TI - Cortical somatosensory evoked potentials in cows. AB - A method was developed to record cortical somatosensory evoked potentials (SEP) from thoracic and pelvic limb stimulation in cows. Recordings were similar in latency and amplitude to those reported for horses. Correction for conduction pathway length did not alter the average latency values because the cows of the study were uniform in size; however, the data provided will enable use of this normative data with smaller or larger individual animals. Although latency variability for the SEP peaks was low, variability of the amplitude measurements was high. This observed variability was similar to that seen in other species. Validity of the recorded responses was indicated by lack of a tibial nerve SEP in 1 cow that had been given a tibial nerve conduction block, using lidocaine, and by repeatability of the response in 2 recordings taken 1 year apart in the same cow. PMID- 1416368 TI - Effects of low-dose aspirin and specific thromboxane synthetase inhibition on whole blood platelet aggregation and adenosine triphosphate secretion in healthy dogs. AB - Platelet aggregation and adenosine triphosphate (ATP) secretion in response to arachidonic acid (10 microM) or collagen (5 micrograms/ml) were compared in healthy, adult female Beagles treated with low-dosage aspirin (3.5 mg/kg of body weight, PO, q 12 h for 7 treatments) or with CGS 12970, a specific thromboxane synthetase inhibitor (10 mg/kg, PO, q 8 h for 10 treatments). Platelet aggregation was assessed in whole blood by use of an electrical impedance method. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood from nontreated dogs resulted in significantly (P less than 0.001) increased impedance, but had no effect in blood from dogs treated with either aspirin or CGS 12970. Treatment with CGS 12970 or aspirin significantly (P less than 0.001) decreased platelet ATP secretion in response to arachidonic acid, compared with baseline values; however ATP secretion in aspirin treated dogs was significantly (P less than 0.01) less than ATP secretion in CGS 12970-treated dogs. Differences in platelet aggregation were not observed between control dogs and aspirin- or CGS 12970-treated dogs in response to collagen as an aggregant, however, collagen-induced platelet ATP secretion was significantly (P less than 0.001) decreased in dogs treated with aspirin, compared with control values and values from dogs treated with CGS 12970. In dogs treated orally with 0.1, 0.2, 1.0, or 10 mg of CGS 12970/kg, dose-dependent inhibition of arachidonic acid-induced platelet aggregation was observed, with impedance changes not observed at the 10-mg/kg dosage and normal platelet aggregation associated with the 0.1-mg/kg dosage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416369 TI - Serum free and total iodothyronine concentrations in dogs with hyperadrenocorticism. AB - Serum concentrations of total and free thyroxine (T4 and FT4, respectively), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3) were measured in 42 dogs with hyperadrenocorticism, and were compared with values determined in clinically normal dogs. Mean total T4 concentration in dogs with hyperadrenocorticism (14.3 nmol/L) was significantly (P less than 0.001) lower than the normal value (25.7 nmol/L), with 38% of the dogs having low serum T4 concentration. Although 16 (38%) of the 42 dogs with hyperadrenocorticism had a high FT4 fraction, indicative of diminished serum T4 binding, normal FT4 concentration was found in only 6 of the 16 dogs (38%) with low total T4 values. Mean serum T3 concentration in dogs with hyperadrenocorticism (0.79 nmol/L) was also significantly (P less than 0.001) lower than the normal value (1.16 nmol/L), with 39% of the dogs having T3 values below the normal range. Individual T3-to-T4 and T3-to-FT4 ratios, indices of T3 production and/or clearance, were above the normal range in 29 and 24% of dogs with hyperadrenocorticism, respectively. Mean reverse T3 concentration in dogs with hyperadrenocorticism (0.17 nmol/L) was also significantly (P less than 0.001) lower than the normal mean value (0.39 nmol/L), with 48% of the dogs having reverse T3 values below the normal range. Of the 21 dogs in which all iodothyronines were measured, 6 (29%) had undetectable values for all hormones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416370 TI - Measurement of total volume and protein concentration of intrauterine secretion after intrauterine inoculation of bacteria in mares that were either resistant or susceptible to chronic uterine infection. AB - Undiluted uterine secretion was used to determine the concentration of total protein and the accumulated volume of uterine secretion after a bacterial inoculation in mares susceptible and resistant to chronic uterine infection (CUI). The uterus of 6 susceptible and 5 resistant mares was inoculated with 5 x 10(6) Streptococcus zooepidemicus on the third day of estrus. Using a tampon inserted in the uterus, secretions were sampled at 5, 12, 24, and 36 hours after inoculation, followed by intrauterine lavage with phosphate buffered saline solution. The concentration of protein was determined in the undiluted secretion as well as in the uterine washing and the total amount of accumulated uterine secretion was calculated. Protein concentrations in plasma were compared before and after absorption by the tampon. Protein concentration of plasma before and after absorption by the tampon did not differ. Mares susceptible to CUI accumulated significantly (P less than 0.001) more fluid in the uterus than mares resistant to CUI, and uterine washings from the resistant mares were significantly (P less than 0.05) more dilute than those from the susceptible mares. Significant differences in protein concentrations between susceptible and resistant mares were not found. It was concluded from this study that the described method to sample undiluted uterine secretion was practical and reliable for the analysis of protein concentration. Various concentrations of uterine secretions in washings from susceptible and resistant mares emphasizes the importance in using undiluted uterine secretions or dilution markers in washings when intrauterine products are analyzed. PMID- 1416371 TI - Effect of head and neck position on respiratory mechanics in horses sedated with xylazine. AB - We studied the temporal changes in respiratory mechanics associated with xylazine administration (1.1 mg/kg of body weight, IV) in standing horses (experiment 1), and determined the effects of head and neck position (experiment 2) and atropine administration (experiment 3) on the observed changes. Thoroughbred geldings, 3 to 5 years old (5 in experiment 1, 4 in experiments 2 and 3) were used. Flow rates were obtained from a pneumotachograph and a differential transducer attached to a tight-fitting mask. Electronic integration of the flow signal gave tidal volume. Total pulmonary pressure (PL) was defined as the difference between esophageal pressure, measured with a balloon sealed to the end of a polyethylene catheter, and mask pressure. In experiment 3, a blunt cannula positioned in the dorsal third of the eighth or tenth intercostal space was used to estimate transpulmonary pressure. Lateral tracheal pressure was measured, using a polypropylene catheter inserted percutaneously in the midextrathoracic tracheal lumen. Upper and lower airway pressures were defined as the difference between mask pressure or transpulmonary pressure and lateral tracheal pressure, respectively. Five observations were made: (1) There was a significant (P less than 0.05) increase in PL from 10 to 40 minutes after administration of xylazine. (2) Although an overall agreement between head and neck position and PL was detected, the maximal PL value was not always obtained with lowest head and neck position. (3) Lower and upper airway resistance increased with low head carriage, with a greater increase in upper airway resistance resulting in a decrease in lower to total airway resistance ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416372 TI - Pharmacokinetics and local tolerance of a long-acting oxytetracycline formulation in camels. AB - Disposition and local tolerance of a new oxytetracycline (OTC) long-acting formulation were evaluated in camels by measuring the dynamics of creatine kinase. Six camels (Camelus dromedarius) were administered OTC by IV and IM routes according to a 2-period cross-over, study design. Serum OTC concentration was measured, using a microbiological assay procedure. After IV administration (5 mg/kg of body weight), mean residence time was 7.7 +/- 2.8 hours, steady-state volume distribution was 706.1 +/- 168.6 ml.kg-1 and serum clearance was 75.3 +/- 23.2 ml.kg-1.h-1. After IM administration of the long-acting OTC formulation (10 mg/kg), maximal OTC concentration (3.49 +/- 0.44 micrograms.ml-1) was observed after 7.3 +/- 3.5 hours; the mean systemic availability was near 100%, and serum concentration greater than 0.5 micrograms.ml-1 was maintained for about 72 hours. After IM administration, mean control serum activity of creatine kinase was multiplied by a factor of 3.36 +/- 1.55; at 72 hours after OTC administration, the serum creatine kinase activity returned to control values. It was concluded that OTC is an antibiotic of potential interest in camels and that a dosage regimen of 10 mg.kg-1 deserves attention when using a long-acting formulation that has good local tolerance and near total systemic availability. PMID- 1416373 TI - Effect of repeated doses of albendazole on enantiomerism of its sulfoxide metabolite in goats. AB - Five adult Saanen goats were dosed orally 3 times with albendazole (2.5 mg/kg of body weight) at 24-hour intervals, and blood samples were taken by jugular venapuncture at standardized intervals. Plasma was analyzed to determine concentrations of S-oxidation metabolites, and a chiral column was used for enantiomeric discrimination of the sulfoxide metabolite of albendazole. Marked changes were evident between the first and subsequent plasma profiles concerning, on one hand, the proportions of sulfoxide and sulfone metabolites concentrations and, on the other hand, the enantiomeric balance of sulfoxide metabolite. These correlated phenomena may be explained by the following arguments: the enzyme responsible for sulfoxidation is mainly a flavine-containing monooxygenase, whereas the enzyme responsible for sulfonation is a cytochrome-dependent monooxygenase; the latter, but not the former, is induced by albendazole; the enantioselectivities of both enzymic systems are opposite, the flavine produces the (+) sulfoxide, whereas the cytochromes can use as a substrate, specifically, the (-) sulfoxide. PMID- 1416375 TI - Effects of allergen challenge on plasma concentrations of prostaglandins, thromboxane B2, and histamine in calves infected with bovine respiratory syncytial virus. AB - To examine the influence of allergen-induced type-1 hypersensitivity on the pathogenesis of bovine respiratory syncytial virus (BRSV) infection, we sensitized calves by aerosol to Micropolyspora faeni (MF) and challenge exposed them during infection with BRSV. The development of MF-specific IgE serum concentrations was confirmed by ELISA. The dynamics of arachidonic acid metabolism and histamine release during a type-1 hypersensitivity reaction in the bovine lung were studied by quantitating the concentrations of prostaglandin (PG)E2, PGF2 alpha, PGI2 as 6-keto-PGF1 alpha, thromboxane (TX) A2 as TXB2, and histamine in plasma of BRSV-infected and/or MF-sensitized/challenge-exposed calves. Four treatment groups were established: (1) BRSV infection only, (2) aerosol sensitization to MF followed by BRSV infection and aerosol challenge exposure to MF, (3) MF aerosol sensitization and challenge exposure without BRSV infection, and (4) aerosol sensitization to MF followed by BRSV infection without MF challenge exposure. Significantly increased concentrations of PGI2 were associated with MF aerosol exposure, particularly when combined with BRSV infection in group 2. After MF challenge exposure, TXB2 concentrations were significantly greater in the virus and MF challenge-exposed group 2. Individual calf data for the change in MF-specific IgE concentration between the first and second MF challenge exposures and the change in PGE2 concentration 30 minutes after the second MF challenge exposure had a highly significant direct correlation. Histamine concentrations were significantly greater in calves infected with BRSV than in uninfected controls regardless of MF exposure. These data further substantiate the thesis that implicates type-1 hypersensitivity as a pathogenic mechanism in BRSV-related disease. PMID- 1416374 TI - Evaluation of a one-hour saline diuresis protocol for administration of cisplatin to dogs. AB - A study was undertaken to determine the toxic effects of cisplatin, an antineoplastic agent, when administered immediately after a 1-hour saline diuresis. Four treatments with cisplatin (70 mg/m2 of body surface, q 3 wk) were administered IV to 6 healthy dogs over a 20-minute period after 0.9% NaCl (saline) solution was administered IV for 1 hour at a volume of 132 ml (kg)0.75. Each dog vomited at least once within 8 hours after each treatment was administered. Clinical status, body weight, and food consumption were normal throughout the 12-week study for 5 of the 6 dogs. The sixth dog developed acute renal failure and became acutely blind and deaf within 3 days after the fourth treatment with cisplatin. Serum electrolyte, creatinine, and urea nitrogen values remained within established normal limits in all dogs immediately prior to each treatment, and in 5 of 6 dogs evaluated 3 weeks after the final treatment. The serum creatinine value (3.3 mg/dl) obtained from the Beagle euthanatized 2 weeks after the fourth treatment was above established normal values. Despite normalcy for all but 1 of the creatinine values, serum creatinine concentration obtained 3 weeks after the final treatment with cisplatin was significantly (P = 0.0001) higher than pretreatment values. When compared with data from all other evaluation periods, significant decreases in glomerular filtration rate, as determined by exogenous (P less than or equal to 0.0001) and endogenous (P less than or equal to 0.0001) creatinine clearance testing, were identified 3 weeks after the fourth treatment with cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416376 TI - Protein kinase-C activity in phorbol myristate acetate-stimulated neutrophils from newborn and adult cattle. AB - Neutrophils from newborn calves have been shown to be deficient in ability to generate superoxide anion (O2-) after stimulation of the respiratory burst enzyme with the phorbol ester, phorbol 12-myristate 13-acetate (PMA). This compound activates the O(2-)-generating enzyme of bovine neutrophils through a pathway involving protein kinase C (PKC). To investigate the biochemical basis underlying this functional difference between neutrophils from newborn and adult cattle, we measured and compared the activity of the enzyme PKC in nonstimulated and PMA stimulated bovine neutrophils. Neutrophils from newborn calves (n = 5) and adult cows (n = 5) were stimulated with various concentrations of PMA (0, 10, 100, and 500 ng/ml) for 3 minutes, and PKC activity was assayed in the cytosolic and the membrane fractions. In nonstimulated cells, most PKC activity was detected in the cytosolic fraction of neutrophils from newborn and adult cattle. Activity of PKC in the cytosol was dependent on the presence of added calcium and phospholipids, whereas membrane-associated PKC in nonstimulated cells did not have such dependence. Significant differences in PKC activity were not observed between newborn and adult cattle in either the cytosolic or the membrane fractions from nonstimulated cells. Stimulation with PMA caused redistribution of PKC activity in the cell (translocation) in newborns and adults, consisting of decrease in cytosolic PKC activity and increase in membrane-associated PKC activity. Similar to that in nonstimulated cells, PKC activity in cytosolic fractions from PMA stimulated neutrophils was dependent on the presence of cofactors (calcium and phospholipids), whereas PKC activity in the membrane did not have such requirement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416377 TI - Immunolocalization of epidermal growth factor (EGF) and EGF receptors in the porcine upper gastrointestinal tract. AB - The factors controlling growth and maturation in the porcine gastrointestinal tract are not well understood. Epidermal growth factor (EGF) is a polypeptide that has been implicated in the control of gastrointestinal tract growth, maturation, and protection in other species. Immunoreactive EGF (IR-EGF) and EGF receptors (EGF-R) were histochemically identified in formalin-fixed tissues of the upper digestive tract of 1-, 3-, 7-, 14-, 21-, and 28-day-old pigs. The ductal epithelium consistently contained IR-EGF in the parotid salivary gland of pigs of all ages and in the mandibular salivary gland in pigs greater than or equal to 7 days old. Immunoreactive EGF was detected in the mucosal epithelium of the esophagus and nonglandular portion of the stomach, and in the pancreas and liver in all pigs. Gastric gland IR-EGF was inconsistently detected in pigs less than 14 days old and was consistently observed in all older pigs. Enterocyte EGF immunoreactivity was usually weak and was variably detected in the duodenum of pigs less than or equal to 7 days old and in the jejunum of pigs less than or equal to 14 days old, but was consistently observed in older pigs. Ileal immunoreactivity was erratic. Immunoreactive EGF-R were identified in the esophageal epithelium of all pigs, and in the nonglandular gastric and glandular gastric mucosa of all pigs, except for two 7-day-old pigs and one 7-day-old pig, respectively. Immunoreactive EGF-R were detected in the duodenal, jejunal, and ileal enterocytes of pigs of all ages examined. PMID- 1416378 TI - Cytogenetic characterization of the Madin-Darby bovine kidney cell line. AB - The permanent bovine cell line, Madin-Darby bovine kidney, was cytogenetically analyzed. Chromosomal staining indicated 52 metaphase chromosomes with variations from 49 to 54. The isochromosomes 5, 12, and 13, and centric fusions between chromosomes 1 and 26, 9 and 11, 9 and 24, 17 and 25, 18 and 23, 20 and 24, and 24 and 27 were considered marker chromosomes. PMID- 1416379 TI - Lymphocyte reactivity to antigens of Haemonchus contortus in antigen-inoculated and H contortus-naive lambs. AB - Lambs were inoculated during either fetal or early neonatal life with antigens of Haemonchus contortus (HcAg) third-stage larvae, or ovalbumin (OVA), or were left untreated. By the time lambs were 4 weeks old, blood lymphocytes from all of them responded to HcAg. This was evident in all lambs, regardless of the previous inoculation regimen, although higher response was seen in HcAg-inoculated lambs, compared with naive lambs. Only lambs inoculated with OVA had OVA-specific lymphocyte activity. In HcAg-naive lambs, the maximal HcAg lymphocyte response was observed between the ages of 5 and 25 weeks, with gradual decrease thereafter. In vitro detection of HcAg-reactive lymphocytes was affected by antigen concentration and presence of plasma. Plasma inhibited HcAg-reactive lymphocytes from all lambs at high in vitro antigen concentration and completely abrogated the response in H contortus antigen-naive lambs. PMID- 1416380 TI - Histochemical and morphologic changes of porcine airway epithelial cells in response to infection with Mycoplasma hyopneumoniae. AB - Mycoplasma hyopneumoniae causes pneumonia in pigs. The effect of infection by this organism on histochemical characteristics of airway mucin within epithelial cells was studied. Seven- to 10-week-old pigs were inoculated intratracheally with M hyopneumoniae or culture broth, and lung tissues were collected from inoculated and control pigs at 2, 4, and 6 weeks after inoculation. Tissue sections were stained with periodic acid-Schiff/Alcian blue, pH 2.5 or high iron diamine/Alcian blue. Histologic features of randomly selected bronchi, bronchioles, and submucosal glands were compared in sections stained with periodic acid-Schiff/Alcian blue. Bronchial goblet cell sulfomucin and sialomucin were quantitated by image analysis of sections stained with high iron diamine/Alcian blue. Bronchi and bronchioles of infected pigs contained proportionately fewer goblet cells with mucin at all stages of infection than age matched control pigs. Goblet cells in bronchi of infected pigs contained significantly less total mucin and sialomucin, and significantly more sulfomucin than goblet cells of control pigs. Increased sulfated mucin in bronchial goblet cells may reflect altered glycoprotein production or secretion in response to infection with M hyopneumoniae. PMID- 1416381 TI - Identification of halothane gene carriers by use of in vivo 31P nuclear magnetic resonance spectroscopy in pigs. AB - In vivo muscle 31P nuclear magnetic resonance spectroscopy was performed on 12 homozygous halothane-nonsensitive female pigs and 13 female pigs heterozygous with respect to the halothane gene. Fifteen female pigs of a third line, consisting of heterozygotes and halothane-nonsensitive homozygotes, were also available. Body weight ranged from 12 to 18 kg. Mean decrease in phosphocreatine concentration in the biceps femoris of anesthetized pigs was significantly lower for heterozygous vs homozygous pigs (3.46% vs 5.94%, P less than 0.01) after 40 minutes of halothane exposure (3%; oxygen flow, 3 L/min). Also, a statistically significant difference, with respect to the initial (7.21 vs 7.11, P less than 0.008) and end muscle pH values (7.18 vs 7.06, P less than 0.0002), was observed for homozygous vs heterozygous pigs. By means of canonical discriminant analysis, it was possible to distinguish nonsensitive homozygotes from heterozygotes (P less than 0.0001). When applying this classification method to pigs of the same strain, 2 populations (nonsensitive homozygotes, heterozygotes) emerged, with a proportion of pigs corresponding to the expected value on the basis of breeding records. In contrast to the phenotypic expression of muscular rigidity related to the malignant hyperthermia syndrome, the expression of metabolic variables (phosphocreatine, pH) was shown to be dominant. PMID- 1416382 TI - Managerial risk factors of intramammary infection with Streptococcus agalactiae in dairy herds in Ohio. AB - Dairy herds in Ohio were selected by stratified random sampling for participation in a disease-monitoring study to relate Streptococcus agalactiae intramammary prevalence to herd management and environmental conditions. Of 48 herds studied, 27 herds had at least 1 cow infected with this pathogen. Management and environmental conditions were assessed by direct observation as well as by an interview with the dairy producers. One-way ANOVA or chi 2 analysis, with presence or absence of Streptococcus agalactiae as the dependent variable, was used to test each of 70 independent variables. Variables found significant at P less than 0.20 were further evaluated by use of logistic regression. Our sample size permitted only 4 independent variables to be simultaneously evaluated by logistic regression. The most predictive risk factors were identified as poor teat and udder hygiene, poor environmental sanitation, large herd population, and use of a shared washcloth for premilking cleaning of teats and udders. PMID- 1416383 TI - U.S. mental health policy. Doomed to fail. AB - Changes in the de facto system of mental health care in the last decade reflect organizational and entrepreneurial responsiveness to changes in health policy, not mental health policy. Various other actions described here reduced statutory or institutional leadership roles in mental health and increased the pace at which mental health policy was becoming dependent on health policy. In turn, U.S. health policy in the 20th century has been inherently flawed. The short-term general hospital--the "doctors' workshop"--emphasizing acute care and surgery, has been the cornerstone of U.S. health policy throughout the 20th century. The mimicry of health services by mental health leads to demonstrably more expensive and less effective mental health care and dooms mental health policy to failure. PMID- 1416384 TI - The debt of neuropsychology to the epilepsies. AB - Both neuropsychology and psychology in general have been enhanced markedly by brain-behavior models derived from the study of the epilepsies. A significant body of neuropsychological concepts originated or were confirmed through epilepsy based treatment and research. These concepts include the peri-Rolandic homunculus, the role of the hippocampal-temporal lobe complex in cognitive memory, hemisphere plasticity for speech in childhood, the intracarotid amytal procedure for determining hemisphere memory patency, and hemisphere-based models of cognition confirmed through human commissurotomy. Personality and social emotional research in epilepsy are additional areas in which new conceptual models grounded in psychological science can both repay our debt to the epilepsies and provide much needed psychological research and treatment. PMID- 1416385 TI - Childhood epilepsy and the role of psychology. AB - The relatively long history of psychology's involvement in the field of epilepsy is discussed. The view of epilepsy is that of a chronic disorder with onset in childhood, at a time when normal development is at risk for interference from the direct and secondary aspects of repetitive seizures, the neurological abnormalities from which they arise, and the clinical interventions that attempt to control them. The objective and scientifically based methods of psychology are viewed as particularly well suited to these topics. Past efforts by psychologists have increased understanding of the syndrome that is epilepsy, and have paved the way for opportunities to further contribute to the theoretically and practically important problems associated with epilepsy. PMID- 1416386 TI - Psychopathology in epilepsy. The role of psychology in altering paradigms of research, treatment, and prevention. AB - This article offers a brief review of the literature examining epilepsy and abnormal behavior. The generally accepted concept of epilepsy as a high psychiatric risk disorder is reexamined in light of research that has investigated the influence of selection bias. A conceptual model that organizes the known or postulated risk variables (neurological, psychosocial, and medication) is presented, with emphasis on psychology's potential contribution. PMID- 1416387 TI - The role of neuropsychology in the assessment and treatment of persons with epilepsy. AB - Several areas of current interest in the neuropsychology of epilepsy are briefly reviewed in this article. These include variables pertaining to seizures, seizure history, antiepileptic drugs, and methods of neuropsychological evaluation. It is apparent that epilepsy is a multifaceted area: Psychologists not only can be of great assistance to patients with this condition, but may also learn a great deal from this complex disorder. PMID- 1416388 TI - Inhaled platelet-activating factor causes pulmonary neutrophil sequestration in normal humans. AB - Inhaled platelet-activating factor (PAF) causes bronchoconstriction and transient peripheral neutropenia in humans. We studied eight normal subjects to investigate whether inhaled PAF caused pulmonary neutrophil sequestration. All subjects received autologous 99mTc-red cells as a blood pool marker, seven received 111In neutrophils, and one received 111In-platelets. Six subjects inhaled 48 micrograms of PAF. There was immediate pulmonary sequestration of 111In-neutrophils, maximal (218% baseline) at 6 min (p less than 0.001), returning to normal by 3 h. There was no change in circulating platelet count or pulmonary 111In-platelet transit. Methacholine inhalation caused equivalent bronchoconstriction to PAF, but it had no effect on neutrophil count or pulmonary 111In-neutrophil activity. We have demonstrated pulmonary neutrophil, but not platelet, sequestration after PAF. This supports a role for PAF as an inflammatory mediator in humans. This may be a useful model for exploring pulmonary neutrophil kinetics and preinflammatory processes. PMID- 1416389 TI - Tachykinins increase respiratory clearance of 99mTc-DTPA. Mechanisms of action. AB - We investigated the effects of tachykinins on the respiratory clearance of 99mTc DTPA (RC-DTPA) in anesthetized and ventilated guinea pigs. We measured the change in RC-DTPA and in maximal pulmonary insufflation pressure (PIPmax) induced by substance P, neurokinin A, and capsaicin. Substance P, neurokinin A, and capsaicin increased both PIPmax and RC-DTPA in a concentration-dependent fashion. Substance-P- and capsaicin-induced increases in RC-DTPA were unaffected by pretreatment with atropine. Bilateral vagotomy attenuated substance-P-induced change in both RC-DTPA and PIPmax by approximately 70 and 50%, respectively. Capsaicin-induced change in RC-DTPA and PIPmax were slightly but not significantly reduced by bilateral vagotomy. The bronchodilator, salbutamol, dramatically reduced increase in RC-DTPA and in PIPmax induced by substance P, neurokinin A, and capsaicin, but it had no effect on increases in RC-DTPA and PIPmax generated by application of a positive end-expiratory pressure. We conclude that (1) tachykinins increase respiratory clearance to the solute, and (2) tachykinin-induced increase in RC-DTPA is not mediated by cholinergic neurotransmission but rather by the bronchoconstrictor effect of neuropeptides. PMID- 1416390 TI - 31P-NMR study of skeletal muscle metabolism in patients with chronic respiratory impairment. AB - To evaluate the energy metabolism of peripheral skeletal muscle during exercise in patients with chronic respiratory impairment, the 31P-nuclear magnetic resonance (NMR) spectra of forearm muscle were investigated in nine patients and nine age-matched control subjects. We calculated the phosphocreatine (PCr) to PCr + inorganic phosphate (PI) ratio, the time constant of PCr recovery and the intracellular pH. The exercise consisted of repetitive hand grips against a 2-kg load every 3 s for 6 min (0.33 W). The patients showed a marked decrease in the PCr/(PCr + PI) ratio and pH in the muscle during exercise in contrast to the control subjects whose PCr/(PCr + PI) showed a minor decrease without any change in pH. The relationship between PCr utilization and pH demonstrated that anaerobic glycolysis switched on earlier in patients with chronic respiratory impairment. A split PI peak was observed in five of nine patients during exercise. The PCr/(PCr + PI) ratio during the last minute of exercise correlated significantly with the vital capacity (% predicted), with the FEV1/FVC, with the body weight, with the maximum strength of hand grip, and with the muscle mass. The results indicate impaired oxidative phosphorylation and the early activation of anaerobic glycolysis in the muscles of patients with chronic respiratory impairment. Several factors related to chronic respiratory impairment, such as disuse, malnutrition and dysoxia, would contribute to the metabolic changes observed in the muscles examined. PMID- 1416391 TI - Respiratory muscle strength in hyperthyroidism before and after treatment. AB - We undertook this study to investigate respiratory muscle strength in relation to thyroid function in 20 thyrotoxic patients and in a group of 20 normal subjects matched for age and sex. Global respiratory muscle strength was assessed by measuring mouth pressure during maximal static inspiratory (PImax) and expiratory (PEmax) efforts. We also measured VC, FVC, and FEV1 as well as thyroid-related hormones (T3, T4, TSH). Measurements were made once in normal subjects and twice in thyrotoxic patients, before and 3 months after medical treatment. Our results showed that both maximal pressures were significantly reduced (p less than 0.0001) before treatment in thyrotoxic patients in relation to the mean values of the normal subjects (p less than 0.0001), and they increased significantly (p less than 0.0003) after treatment. Lung volumes were significantly reduced (p less than 0.0001) before and increased significantly (p less than 0.008) after treatment. The ratio FEV1/FVC did not change. A statistically significant linear relationship was found when PImax of patients with thyrotoxicosis before treatment and of normal subjects were plotted against thyroid hormones (T3, T4) (r = -0.746 and r = -0.745, respectively, p less than 0.001). Similarly, a statistically significant linear relationship was found between PEmax and T3 and T4 (r = -0.837 and r = -0.838, respectively, p less than 0.001). No relationship was found between maximal pressures and TSH. Finally, a significant linear relationship was found between PImax and PEmax (r = 0.872, p less than 0.001). Our results confirm that in thyrotoxicosis respiratory muscle weakness occurs that affects both inspiratory and expiratory muscles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416392 TI - The effects of transcutaneous electrical stimulation during wakefulness and sleep in patients with obstructive sleep apnea. AB - Upper airway (UA) collapse in obstructive sleep apnea (OSA) is considered in part to result from the decrease in UA dilator muscle tone that occurs during sleep. We hypothesized that augmentation of UA muscle function by transcutaneous electrical stimulation (TES) might function to enlarge UA size during wakefulness and/or prevent UA collapse during sleep in patients with OSA. Eight male patients with OSA were studied both awake and asleep, with TES administered to the submental region in two patients and to both the submental and subhyoid regions in six patients. Fast-CT scans obtained at FRC and end-inspiration (VTei) demonstrated increased UA size with tidal breathing, p less than or equal to 0.05. The active generation of -10 cm H2O pressure at FRC substantially decreased UA size, p less than or equal to 0.001. However, no changes in UA size were detected at either FRC or VTei with TES applied at 50 and 100% of the maximal tolerated intensity. The collapsibility of the UA in response to the generation of -10 cm H2O pressure was also unchanged by TES. In contrast to the lack of effect of TES on UA size, voluntary protrusion of the tongue increased cross sectional area (CSA) of the orohypopharyngeal (OHP) segment of the UA, p less than 0.05, and to a lesser extent the CSA of the distal velopharyngeal segment, p = 0.06. When applied during sleep, TES failed to prevent or improve either sleep disordered breathing or sleep architecture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416393 TI - Morphometric changes during the early airway response to allergen challenge in the rat. AB - The purpose of this study was to determine the relative contributions of airway wall edema and smooth muscle contraction to the early response (ER) of allergic bronchoconstriction. Brown Norway rats, 6 to 7 wk old, were sensitized with ovalbumin (OA). Anesthetized rats were challenged with either OA or saline 2 wk later. Pulmonary resistance (RL) was measured every minute until either it increased to 150% of the baseline, defined as a significant ER, or until 15 min elapsed. Eight OA-challenged test rats with a significant ER and eight saline challenged control rats were used for morphometric studies. The lungs were quick frozen with liquid nitrogen, processed with freeze substitution, and sagittal sections (5 microns) were stained with hematoxylin and eosin. The airway lumen subtended by the epithelial basement membrane (LuB) and cross sectional airway wall area (AW) of all airways were measured by camera lucida and digitization. The LuB and AW of each airway was standardized for size by dividing by the ideal airway lumen (LuBideal), which was calculated from the length of basement membrane, assuming a perfect circle in the unconstricted state. The cumulative frequency distribution of the LuB/LuBideal for the airways from test rats was shifted to the left compared with the control rats (p less than 0.01), indicating airway narrowing after challenge. Airway narrowing increased as a function of airway size. Cumulative frequency distributions of AW/LuBideal showed that there was a significant increase in the wall thickness of only the small airways of test animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416394 TI - Idiopathic pulmonary fibrosis. Quantitative assessment of lung pathology. Comparison of a semiquantitative and a morphometric histopathologic scoring system. AB - The objective of this study was to determine the accuracy of a semiquantitative method of assessing the relative degree of cellularity and fibrosis compared with a morphometric analysis of specific histopathologic features in idiopathic pulmonary fibrosis (IPF). Morphometric analysis was performed on biopsy tissue from 20 patients. Morphometry showed that approximately 70% of parenchymal tissue was abnormal: 35% cellular consolidation and fibrosis, 20% honeycomb changes, 10% thick alveolar septa, and 5% small airways within abnormal parenchymal tissue. The prominent components of the abnormal parenchymal tissue were extracellular fibers, an abundance of interstitial cells, and epithelial cell hyperplasia. Correlation between four groupings of pathologic features, identified by a semiquantitative analysis, and each of the components of the parenchymal lesions showed significant correlations between (1) the fibrotic or reparative factor (alveolar wall metaplasia, fibrosis, honeycombing, and smooth muscle and vascular changes) and components of honeycomb lesions (extracellular fibers, interstitial cells, and epithelial injury and repair), and (2) the inflammatory and exudative factor and extracellular fibers in the lesions. These results support that the scoring system used by the pathology panel provides an accurate assessment of pathologic features useful in the assessment of the extent and severity of the histopathologic lesions of IPF. PMID- 1416395 TI - Reperfusion after a two-hour period of pulmonary artery occlusion causes pulmonary necrosis. AB - The role of reperfusion injury in the progression to necrosis in pulmonary embolism was evaluated. To simulate this condition, we used a technique that enables occlusion and reopening of the pulmonary arterial branch supplying the right upper lobe in conscious rats. The rats were divided into five groups: the occlusion group (n = 12), in which the pulmonary artery (PA) branch was occluded without reperfusion; the reperfusion group (n = 12), in which the PA branch was reopened after a 2-h period of occlusion; and the reperfusion-SOD (n = 9), reperfusion-IM (n = 8), or reperfusion-IA-SOD (n = 6) groups, in which superoxide dismutase (SOD), indomethacin (IM), or inactivated SOD (IA-SOD), respectively, was administered during reperfusion. The lungs were removed 24 h after the PA occlusion, and histologic examination was performed. In the occlusion group, the alveolar structure of the right upper lobe was well preserved, and there was no erythrocyte or leukocyte accumulation. The only significant changes compared with the control lobe was the appearance of wavy internal elastic lamina of the PA and slight neutrophil adherence to the endothelial cells. In contrast, the right upper lobe of the reperfusion group disclosed numerous foci of hemorrhagic necrosis, with disrupted alveoli and leukocyte accumulation in all cases. With SOD treatment, the changes compatible with hemorrhagic necrosis were attenuated to the level of the control lobes. However, neither IM nor IA-SOD decreased these changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416396 TI - Effect of cirrhosis on the production and efficacy of pneumococcal capsular antibody in a rat model. AB - We sought to study the immunogenicity of Type 3 pneumococcal capsular polysaccharide (PCP) antigen and the protective efficacy of Type 3 PCP antibodies in a rat model of cirrhosis. Cirrhosis with ascites was induced in male Sprague Dawley rats by weekly gavage with CCl4. Cirrhotic and age-matched control rats were vaccinated with 25 micrograms of Type 3 PCP. Serum antibodies against Type 3 PCP were determined before vaccination and on postvaccination Days 5, 7, 10, 14, 21, 28, and 42 by radioimmunoassay. Maximum concentrations occurred at 7 days in cirrhotic rats and 10 to 14 days in control rats. Geometric mean Type 3 PCP antibody levels (ng AbN/ml) were higher in cirrhotic versus control rats before vaccination (75.9 versus 33.8; p = 0.011) and on post-vaccination Day 5 (626 versus 158; p = 0.008) and Day 7 (1,755 versus 493; p = 0.002). Postvaccination antibody from immunized control and cirrhotic animals provided passive immunity to Type 3 Streptococcus pneumoniae infection in mouse protection studies. Sham immunized and PCP-immunized control and cirrhotic rats were challenged with 10(7) cfu Type 3 S. pneumoniae. Immunization was associated with a greater reduction in postchallenge mortality in control rats (91% reduced to 36%; p = 0.02) compared with cirrhotic rats (100% reduced to 83%; p = 1.0). Thus, the increased serum concentrations of functional, type-specific anticapsular antibody in vaccinated cirrhotic rats does not reverse their impaired resistance to Type 3 pneumococcal pneumonia. PMID- 1416397 TI - Nosocomial bronchopneumonia in the critically ill. Histologic and bacteriologic aspects. AB - To provide a comprehensive description of the histologic and bacteriologic characteristics of human nosocomial bronchopneumonia (BPN), the lungs of 83 critically ill patients decreased after a period of mechanical ventilation were examined in the immediate postmortem period. In addition, the accuracy of the protected minibronchoalveolar lavage (BAL) technique in the diagnosis of nosocomial BPN was evaluated. In each patient, a surgical pneumonectomy was performed at the bedside within 30 min following death. Each pulmonary lobe was sampled and bacteriologically analyzed using semiquantitative cultures in 50 patients and quantitative cultures in 33 patients. The entire lung was histologically analyzed using 5 to 10 slices per lung segment. In 69 patients, the bacteriologic result of a protected mini-BAL performed within 48 h preceding death was compared with histologic and bacteriologic results of study of the lung tissue itself. Histologic lesions of BPN were found in 43 of the 83 lungs examined. These lesions were (1) severe in the majority of patients (confluent BPN, n = 23; lung abscess, n = 6), (2) preferentially found in dependent lung segments, (3) often associated with nonspecific alveolar damage, (4) associated with positive lung cultures in 65% of patients (53% with gram-negative bacteria), (5) polymicrobial in 28% of patients, (6) characterized by a lobar bacterial burden greater than 10(3) cfu/g in 32% of cases. Using semiquantitative bacteriologic analysis, the sensitivity and the specificity of the protected mini BAL in the diagnosis of nosocomial BPN were found to be 70 and 69%, respectively. Protected mini-BAL identified 77% of causative microorganisms of BPN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416398 TI - Bacterial infection in chronic obstructive pulmonary disease. PMID- 1416399 TI - Chest radiography and high resolution computed tomography of the lungs in asthma. AB - CT scans have been studied only in asthmatics who were smokers, and no such study has been performed in patients with chronic uncomplicated asthma where a permanent bronchial destruction is likely to occur after a long course of the disease. The object of the study was to characterize CT-scan abnormalities and determine whether bronchial destructive lesions may be observed. Fifty-seven adults with chronic asthma of variable severity and etiology and 10 normal subjects were studied. None of the subjects smoked. Chest radiographs and HR-CT scans were performed in all patients. To discriminate between reversible and irreversible CT-scan abnormalities, two examinations were made in 10 patients with acute asthma both before and 2 wk after parenteral high dose corticosteroid treatment. The chest radiographs showed the expected abnormalities of asthma in 37.8% of the asthmatics. CT scans were abnormal in 71.9% of the asthmatics. Reversible abnormalities included mucoid impactions, acinar pattern, and lobar collapse. Irreversible abnormalities included bronchiectasis, bronchial wall thickening, sequellar line shadows, and emphysema. Most of these abnormalities are likely to be related to bronchial destruction. PMID- 1416400 TI - Physiologic studies of tracheobronchial stents in airway obstruction. AB - When airway obstruction is due to extraluminal compression and/or dynamic collapse, metal and silicone rubber prosthetic stents may stabilize the affected airway. Through a rigid bronchoscope, we inserted three metal stents in two patients and 18 silicone stents in 15 adult patients with symptomatic tracheobronchial compression and dynamic airway collapse. The underlying cause was malignancy in three patients; benign tracheobronchial malacia in three patients, two of whom refused surgical resection; and tracheobronchial stenosis that developed at the anastomotic site following lung transplantation in 11 patients. Clinical status and lung function studies were analyzed before and after stent insertion. Following stent insertion, airway diameter at least doubled and near normal patency of the affected tracheobronchial tree was achieved in every patient using stents of axial length 4 to 5 cm. The stents were well tolerated clinically, and all patients noted immediate relief of dyspnea. Following stent insertion, the forced vital capacity (FVC) increased from 64 +/- 21% predicted (mean +/- 1 SD) to 73 +/- 19% predicted, p less than 0.1; the forced expiratory volume in 1 s (FEV1) from 49 +/- 25% predicted to 72 +/- 26% predicted, p less than 0.02; the ratio of the FEV1/FVC from 59 +/- 16% to 78 +/- 15%, p less than 0.01; and the maximum flow at 50% expired FVC from 38 +/- 26% predicted to 72 +/- 31% predicted, p less than 0.01. PMID- 1416401 TI - Training programs in adult respiratory disease and training programs in pediatric respiratory disease, 1992 editions. American Thoracic Society/American Lung Association. PMID- 1416402 TI - Isoniazid preventive therapy of tuberculosis: decision analysis considering ethnicity and gender. PMID- 1416403 TI - World lung health: a concept that should become a reality. The ATS Committee on World Lung Health. PMID- 1416404 TI - The increasing problem of asthma in the United States. PMID- 1416405 TI - Interleukin-8 is a major neutrophil chemotactic factor in pleural liquid of patients with empyema. AB - Interleukin-8 (IL-8), a potent neutrophil chemotactic peptide, has been found in association with human disease, but its contribution to chemotactic activity in humans is not yet known. We asked whether IL-8 is present in inflammatory human pleural effusions, and to what extent it contributes to pleural liquid neutrophil chemotactic activity. Because tumor necrosis factor alpha (TNF-alpha) is a strong inducer of IL-8, we also asked whether TNF-alpha was present. For this prospective study, we collected pleural liquid from 51 patients (empyema, 14; parapneumonic, four; tuberculous, eight; malignant, nine; miscellaneous exudative, seven; and transudative, nine), counted pleural neutrophils, and measured IL-8 and TNF-alpha concentrations in the supernatant. To determine the contribution of IL-8 to chemotactic activity in empyema, we measured the neutrophil migration induced by empyemic liquids before and after addition of anti-IL-8 F(ab')2 antibody fragments or control anti-IL-6 F(ab')2. We found that IL-8 concentrations were higher in empyema (61.3 +/- 21.0 ng/ml [SEM]) than in all other effusions (1.1 +/- 0.5 ng/ml) (p = 0.0001). All empyema liquids had IL 8 concentrations above 2.5 ng/ml, which was true for only three of the other 37 effusions (two parapneumonic, one tuberculous). IL-8 levels correlated with the pleural neutrophil count (r = 0.46; p = 0.007) and the neutrophil chemotactic activity of pleural liquid (r = 0.43; p = 0.008). Anti-IL-8 antibodies decreased chemotactic activity in empyema liquids by 65 +/- 5%, whereas the control antibody had no effect (0 +/- 5% decrease) (p = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416406 TI - Heterogeneity of phagocytosis for inhaled versus instilled material. AB - Animal experiments involving lung exposure to particles and toxins often use intratracheal instillation, although inhalation is more physiologically relevant to human respiratory tract exposures. Using nontoxic magnetic particles, we examined the particle content distribution within the macrophage population lavaged from the lungs of Syrian golden hamsters exposed either by inhalation or by intratracheal instillation. One to 3 days after iron oxide particle delivery to the lungs, lung macrophages were harvested from animals in pairs, one exposed by inhalation and one exposed by instillation. The macrophages were then magnetically fractionated according to magnetic iron oxide content by flowing the cell suspension through tubing placed within the magnetic field gradient of an electromagnet. Macrophages that had ingested the largest quantity of magnetic iron oxide preferentially collected adjacent to the tubing wall when the electromagnet was at its lowest current; those with fewer particulates collected at correspondingly higher amperages; those cells that were never pulled out of the flowing stream had little or no magnetic iron oxide content. Our results showed that 80% of the lavaged cell population from animals exposed by inhalation had measurable particle content, whereas by instillation, many cells (70%) received no dose at all. Exposure by inhalation produced a more even distribution of dose among lung macrophages. Macrophage intracellular motions showed a decrease when cell content exceeded 7 to 8% of cell volume. We conclude that the method of particle delivery to lungs can influence the dose distribution among lung macrophages. PMID- 1416407 TI - Diagnosis of Pneumocystis carinii pneumonia by multiple lobe, site-directed bronchoalveolar lavage with immunofluorescent monoclonal antibody staining in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. AB - The yields of both induced sputum examination and bronchoalveolar lavage (BAL) have been reported to be decreased for breakthrough episodes of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients receiving aerosolized pentamidine chemoprophylaxis. This study assessed whether the yield of a single middle or lower lobe BAL could be increased by the utilization of two techniques: (1) indirect immunofluorescent staining with a combination of two murine monoclonal anti-Pneumocystis antibodies in addition to routine toluidine blue O and cytopathologic staining, and (2) the performance of multiple lobe, site-directed BAL (i.e., both upper lobe and middle or lower lobe lavage, including the lobe with the greatest radiographic abnormality). Results of 252 fiberoptic bronchoscopies performed at the National Institutes of Health and the Los Angeles County-University of Southern California Medical Center were analyzed. P. carinii pneumonia was documented in 21 episodes in patients who did not receive prior anti-Pneumocystis chemoprophylaxis and in 41 episodes in patients who received aerosolized pentamidine. Monoclonal antibody staining and multiple lobe, site-directed BAL resulted in similar diagnostic yields for P. carinii in the nonprophylaxis (100%) and aerosolized pentamidine (98%) groups. If BAL had been performed without monoclonal antibody staining and multiple lobe, site-directed lavage, then the yield would have decreased to 95% in the nonprophylaxis group and to 80% in the aerosolized pentamidine group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416408 TI - Effect of aerosolized pentamidine prophylaxis on the clinical severity and diagnosis of Pneumocystis carinii pneumonia. AB - To determine if the use of aerosolized pentamidine prophylaxis decreases the clinical severity or the sensitivity of diagnostic tests for Pneumocystis carinii pneumonia (PCP), we conducted a retrospective matched cohort comparison study of patients admitted to San Francisco General Hospital with PCP from August 1, 1989, to June 30, 1990. Patients who had received pentamidine prophylaxis during at least the 2 months prior to the diagnosis of PCP were matched with patients who had not received the drug. Matching was based on the number of prior episodes of PCP, sex, age, and risk factors for human immunodeficiency virus infection. As markers of clinical severity, we chose alveolar-arterial oxygen difference, serum lactate dehydrogenase levels, outpatient versus inpatient treatment, length of hospitalization, length of intravenous anti-pneumocystis treatment, development of respiratory failure, in-hospital mortality, and chest radiographic appearance. Although, of the 27 matched pairs identified, significantly fewer of the pentamidine cohort were treated as inpatients, and significantly more of this cohort had upper lobe dominant disease on chest radiograph, we found no other significant differences between markers of clinical severity for the two cohorts. In addition, we found no significant differences in the rate of sputum or bronchoalveolar lavage positivity for P. carinii between the two cohorts. We conclude that, although hospitalization is less common in patients with a history of prophylactic pentamidine use, aerosolized pentamidine prophylaxis does not decrease the clinical severity or the sensitivities of sputum induction or bronchoalveolar lavage as diagnostic tests for PCP. PMID- 1416410 TI - Longitudinal lung function decline in subjects with respiratory symptoms. AB - The relation of respiratory symptoms and lung function has not been extensively investigated. To determine better the rate of FEV1 decline in subjects reporting persistent wheeze, chronic cough, chronic phlegm, and/or dyspnea, longitudinal data from an adult population sample of 3,948 subjects (1,757 men; 2,191 women) followed for 12 yr were analyzed. At the initial and subsequent follow-up visits, subjects completed a standardized respiratory questionnaire and performed spirometry using the same methods and spirometers. Subjects were categorized based on the presence or absence of self-reported respiratory symptoms (persistent wheeze, chronic cough, chronic phlegm, or shortness of breath) at the initial visit. Six-specific linear regression models were fitted to determine the effect of these respiratory symptoms on lung function. In both men and women, reporting of any respiratory symptoms was associated with both a reduction in initial lung function and more rapid decline in height-adjusted FEV1. Furthermore, after adjustment for height, age, and cigarette smoking, men with cough or phlegm and women with cough alone showed accelerated loss in FEV1. Clinicians should be aware of the predictive value of these respiratory symptoms, because therapeutic intervention may modify the associated decline in lung function. PMID- 1416409 TI - Cohort study of human immunodeficiency virus infection in patients with tuberculosis in Nairobi, Kenya. Analysis of early (6-month) mortality. AB - Retrospective studies suggest that the mortality rate from HIV-1-associated tuberculosis is greater than that from tuberculosis alone, but it is not clear if this is due to failure of antituberculosis treatment or to the complications of HIV-1 infection. We have carried out a prospective cohort study of patients with tuberculosis in Nairobi, Kenya, to compare mortality rates, risk factors, and causes of death in HIV-1 positive and HIV-1 negative patients. One hundred seven HIV-1 positive and 174 HIV-1 negative patients with tuberculosis attending two tuberculosis treatment centers in Nairobi were enrolled and followed monthly. Mortality was significantly higher in HIV-1 positive than in HIV-1 negative patients within 6 months of the start of antituberculosis treatment after adjustment for age, sex, and education (rate ratio = 3.8; 95% confidence interval, 1.7 to 8.1; p less than 0.001). Most of the excess mortality occurred after the first month of treatment and was due to nontuberculous infections. Predictors for mortality differed greatly between HIV-1 positive and HIV-1 negative patients. Mortality was greater in HIV-1 positive patients treated with a "standard" regimen for tuberculosis than in HIV-1 positive patients receiving a "short-course" regimen (p = 0.08 when adjusted for all independent risk factors). Tuberculosis control programs in developing countries need to implement "short course" regimens and train health workers to recognize and treat nontuberculous infections to maintain their effectiveness in the face of the HIV epidemic. PMID- 1416411 TI - Relation of dose-response slope to respiratory symptoms and lung function in a population study of adults living in Busselton, Western Australia. AB - For describing bronchial responsiveness, it has been suggested that the dose response slope (DRS), which is the linear slope of the dose-response curve, is a more useful measure of severity than the provoking dose that causes a 20% fall in FEV1 (PD20FEV1). To determine the distribution of DRS measurements and their relation to respiratory illness in adults, we have reanalyzed data collected in 1981 from a random sample of the population of Busselton, Western Australia. We measured bronchial responsiveness to histamine by the rapid method and atopy by skin prick tests to 15 common allergens. Satisfactory bronchial challenge data were recorded for 858 subjects. Subjects were classified as having asthma symptoms by self-reported history or as having chronic airflow limitation by abnormality of lung function. In normal subjects, DRS values were symmetrically distributed on a logarithmic scale so that a value that represented abnormal responsiveness could be calculated. The dose-response slope had a significant independent association with past and current asthma symptoms, smoking history, sex, atopy, and FEV1/FVC ratio but not with chronic airflow limitation. In subjects in whom a PD20FEV1 could not be measured, the DRS had a significant relation to asthma symptoms, smoking history, and FEV1/FVC. Thus, DRS values, which could be obtained for most subjects, contributed additional information to PD20FEV1 values and discriminated more accurately between groups classified according to respiratory history. These data confirm that DRS values should be used in preference to PD20FEV1 values for describing the severity of bronchial responsiveness in populations. PMID- 1416412 TI - The predictive relationship between serum IgE levels at birth and subsequent incidences of lower respiratory illnesses and eczema in infants. AB - Cord serum IgE levels are predictive of subsequent atopic diseases early in life. Lower respiratory illnesses (LRI) have often been included with atopic diseases in infancy but have not been examined as a separate entity for a relation to cord IgE levels. Among 767 healthy newborns in Tucson, Arizona studied longitudinally, cord serum IgE levels were directly related to the subsequent incidence of eczema. In contrast, the incidence of LRI not only failed to show a direct relationship to IgE levels but actually decreased with increasing cord IgE levels from 34.8% in the lowest cord IgE group to 22.2% in the highest IgE group (greater than 1.0 IU/ml IgE; p for trend chi-square less than 0.03). Limiting LRI to those with wheeze did not alter the inverse relationship with IgE levels. The inverse LRI-IgE relationship was strong for non-RSV LRI, whereas RSV LRI had neither a direct nor an inverse relationship. These inverse LRI-IgE relationships were significant for LRI occurring in infants before but not after 6 months of age. Maternal (but not paternal) allergic history was associated with higher cord IgE levels and with an increased incidence of LRI, the latter effect being independent of IgE. This study suggests that most LRI in the first year of life are not early manifestations of an allergic predisposition. PMID- 1416413 TI - Methacholine responsiveness, smoking, and atopy as risk factors for accelerated FEV1 decline in male working populations. AB - Longitudinal lung function data from four occupational health surveys was used to explore the relationship between nonspecific bronchial responsiveness (NSBR) and the rate of decline of FEV1 (RDFEV) and to address other factors that may predict or influence RDFEV. Of the 1,203 subjects with baseline methacholine and lung function data, follow-up data were available for 733 individuals (61%). The data available and data-unavailable groups were well matched with respect to baseline lung function, atopy, and smoking status. Compared with the unavailable group, those available for follow-up were younger (42.5 versus 37.7 yr; p less than 0.0001) and slightly less responsive to methacholine (p less than 0.01). Somewhat unexpectedly, RDFEV was lower in the 30 asthmatic subjects than in the nonasthmatics. Among the nonasthmatic subgroup (96% of those available for follow up), age, occupational group, and baseline FEV1 (% predicted) were independent predictive factors for RDFEV. When these factors were included in the model, RDFEV was found to be increased among current smokers compared with never-smokers or ex-smokers. In the final regression model, a relationship was found between methacholine sensitivity (calculated as a dose-response slope) and RDFEV in nonasthmatics (p less than 0.05). Stratification by smoking status revealed that the relationship between RDFEV and bronchial responsiveness was confined to current smokers and that atopy was an additional risk factor in this subgroup only. This relationship was valid among current smokers in each of the three occupational groups studies. However, reinclusion of the 30 asthmatic subjects in the study population obscured the relationship between NSBR and RDFEV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416414 TI - Association of asthma with use of pesticides. Results of a cross-sectional survey of farmers. AB - We investigated the association of self-reported asthma and pesticide use in 1,939 male farmers. Regardless of age, smoking pack-years, and nasal allergic reactions, the prevalence of asthma was significantly associated with the use of carbamate insecticides (prevalence odds ratio = 1.8, 95% confidence interval: 1.1 to 3.1, p = 0.02). Self-reported asthmatics, in comparison with nonasthmatics, had significantly lower mean values for lung function test variables after adjusting for age and height and a higher prevalence of respiratory symptoms. These findings raise the possibility that exposure to agriculture chemicals could be related to lung dysfunction in exposed farmers. PMID- 1416415 TI - A community-based study of the epidemiology of asthma. Incidence rates, 1964 1983. AB - To determine whether the incidence of asthma had increased in Rochester, Minnesota, from January 1, 1964 through December 31, 1983, we used a population based computer-linked medical diagnosis system to identify individual medical records with diagnosis of asthma or other conditions mimicking asthma. All records were reviewed using explicit predetermined diagnostic criteria; we identified 3,622 incident cases of asthma, including definite asthma (n = 1,547), probable asthma (n = 952), and single wheezing episodes (n = 1,123). The annual age- and sex-adjusted incidence of definite + probable asthma rose from 183 per 100,000 in 1964 to 284 per 100,000 in 1983. This rise was entirely accounted for by increased incidence rates in children and adolescents (age range, 1 to 14 yr); incidence rates for infants younger than 1 yr of age and for adults remained constant. For definite + probable asthma cases, the incidence rates for males were higher than for females from infancy through 9 yr of age and for persons older than 50; incidence rates for females were higher than for males from 15 through 49 yr of age. The median age at onset was 3 yr for males and 8 yr for females. We conclude that asthma begins in early childhood, with a higher incidence and earlier onset in males, and that the increase in incidence rates seen from 1964 to 1983 occurred only in children and in adolescents. PMID- 1416416 TI - Maximal airway narrowing in a general population. AB - To characterize airway responses in a population sample, respiratory symptoms, smoking habits, and changes in FEV1 (delta FEV1) to inhaled methacholine (maximal cumulative dose of 196 mumol or maximal decrease in FEV1 of 50%) were recorded in 201 subjects. From each dose-response curve the plateau (delta FEV1 less than or equal to 5% over two or more dose steps) response, the maximal response (average of responses on the plateau or maximal delta FEV1 when no plateau was present), slope, and PD20 (dose required to cause delta FEV1 greater than 20%) were derived. The pattern of dose-response curves was a continuous change from being flat (maximal delta FEV1 less than or equal to 5%), becoming steeper with a plateau that occurred at a greater change in FEV1 as the curves were shifted more to the left, to being the steepest without a plateau response. Maximal delta FEV1 was significantly related to the PD20 (r = -0.64, p less than 0.001) and the slope (r = 0.63, p less than 0.001). A history of doctor-diagnosed asthma or wheeze in the last 12 months was related to the level of the maximal delta FEV1 and to PD20. Likelihood ratios [LR = sensitivity/(1-specificity)] for asthma or wheeze were higher for a maximal delta FEV1 of 50% plus a PD20 of 4 mumol (LR = 6.5) or 1 mumol (LR = 7) than for either alone. Subjects without reported asthma or wheeze more often had a plateau on the dose-response curve (76%) than those with a positive history (49%, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416417 TI - Alveolar macrophage accessory cell function in bronchial asthma. AB - The capacity of peripheral blood monocytes and alveolar macrophages (AM) obtained by bronchoalveolar lavage (BAL) to present recall antigens, namely, tuberculin purified protein derivative (PPD) or streptokinase-streptodornase (SKSD), to highly purified autologous T-cells has been studied in 11 asthmatic and 11 healthy, nonatopic normal subjects. In the asthmatic group, AM accessory cell function was variable, and most subjects were unable to present either recall antigen as effectively as blood monocytes, although one asthmatic subject demonstrated larger proliferative responses than blood monocytes for both antigens. AM accessory cell activity was not antigen-specific, and there was a correlation between accessory cell efficacy for the two antigens (r = 0.92; confidence interval, 0.53 to 0.98). Furthermore, a correlation existed between the percentage lymphocyte count in the BAL fluid and the ratio of macrophage to monocyte antigen-presenting capability for both PPD (r = 0.92; 95% confidence interval, 0.83 to 0.99) and SKSD (r = 0.90; 95% confidence interval, 0.45 to 0.98). In the normal subjects, AM were also unable to act effectively as accessory cells for the presentation of PPD and SKSD in the majority of subjects. No correlation existed between the percentage lymphocytes in BAL fluid and the ratio of AM to monocyte accessory cell function. These results suggest an association between AM accessory function and the presence of BAL lymphocytes in bronchial asthma. PMID- 1416418 TI - Effect of atrial natriuretic peptide given by intravenous infusion on bronchoconstriction induced by ultrasonically nebulized distilled water (fog). AB - Atrial natriuretic peptide (ANP) is secreted by cardiac atria and lung tissue; it has a bronchodilator action in normal subjects and patients with asthma and has been shown to protect against histamine-induced bronchoconstriction in patients with asthma. Bronchoconstriction caused by inhalation of ultrasonically nebulized distilled water (fog), in contrast to histamine-induced bronchoconstriction, has features in common with exercise-induced asthma but can be given more easily in a dose-response fashion. The present study aimed to determine the effect of elevated plasma ANP concentrations on the bronchoconstrictor response to inhalation of fog. Eight patients with atopic asthma were studied, mean baseline FEV1 3.00 1, equivalent to 89% (range 76-103%) predicted. The provocation dose of fog producing a 25% fall in FEV1 (PD25) was determined for each subject. On 4 study days, subjects received an intravenous infusion of placebo or ANP at a rate of 1.25, 3.0, or 10.0 pmol/kg/min in randomized, double-blind manner for 30 min to allow steady-state plasma concentrations to be achieved; the PD25 fog was then administered and FEV1 recorded over 30 min. Mean (SEM) baseline plasma ANP concentration was 19.3 (4.1) pg/ml and increased to 39.4 (6.6), 106.4 (11.1), and 445.9 (105.4) with the three rates of ANP infusion. The highest rate of infusion increased prechallenge FEV1 by 8.7 (2.4)% (p less than 0.01), but the lower rates of infusion had no effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416419 TI - The effect of platelet activating factor antagonist on ozone-induced airway inflammation and bronchial hyperresponsiveness in guinea pigs. AB - We investigated the role of platelet-activating factor (PAF) in ozone-induced airway responses by examining the effects of L659,989, a potent PAF antagonist, on bronchial hyperresponsiveness and airway inflammation. Twenty-four male guinea pigs were studied in four equal groups. Total lung resistance (RL) in intubated and spontaneously breathing animals was measured in a constant-volume body plethysmograph. Dose-response curves to methacholine were determined in all animals at the start of the experiment. These were repeated on a separate day after the following types of treatments: air exposure in Group 1, intraperitoneally administered alcohol and air exposure in Group 2; intraperitoneally administered alcohol and ozone exposure in Group 3, and intraperitoneally administered L659,989 (a specific PAF antagonist), 5 mg/kg dissolved in alcohol, and ozone exposure in Group 4. Bronchoalveolar lavage (BAL) was performed after the second methacholine challenge, and the bronchial mucosa was also examined for inflammatory cells. Exposure to 3 ppm ozone for 2 h resulted in a three-doubling concentration increase in bronchial responsiveness, which was not significantly inhibited by prior treatment with L659,989. Ozone induced a 1.8-fold increase in BAL total cell count, increased eosinophilic influx into the airways, and increased eosinophilic infiltration in the bronchial mucosa, which were all not inhibited by L659,989 pretreatment. The results suggest that PAF may not have an essential role in ozone-induced airway hyperresponsiveness and nonallergic airway inflammation. PMID- 1416420 TI - A novel leukotriene antagonist, ONO-1078, inhibits and reverses human bronchial contraction induced by leukotrienes C4 and D4 and antigen in vitro. AB - ONO-1078, 4-oxo-8(-)[p-(4-phenylbutyloxy)benzoylamino]-2-(tetrazol-5-y l)-4H-1 benzopyran hemihydrate, is a novel compound that has been shown to be a leukotrienes C4 and D4 (LTC4, LTD4) antagonist in the guinea pig airways. We studied the ability of ONO-1078 to inhibit and reverse the contraction of isolated human bronchus induced by LTC4, LTD4, and antigen. The human bronchial tissues were prepared from patients undergoing surgery for lung cancer, and they were placed in organ baths. ONO-1078 (10(-8) to 10(-6) M) produced a concentration-dependent inhibition of LTC4 and LTD4 concentration-response curves. In the presence of l-serine borate complex, which inhibits the conversion of LTC4 to LTD4 by gamma-glutamyl transpeptidase, ONO-1078 significantly inhibited the LTC4-induced contraction, suggesting that ONO-1078 is an antagonist of both LTC4 and LTD4. ONO-1078 (10(-6) M) also significantly reversed an ongoing contraction induced by LTC4 (10(-7) M). The inhibitory effect of ONO-1078 on LTC4 induced contraction was at least 100 times more potent than that of FPL 55712, the first discovered LTC4 and LTD4 antagonist. To study the effect of ONO-1078 on the contraction induced by antigen challenge, bronchial tissues were incubated for 2 h with serum of high specific IgE against house dust from an asthmatic patient. House dust antigen was added to the sensitized bronchial tissues after incubation with ONO-1078 (10(-6) M) or histamine H1 antagonist pyrilamine (10(-6) M), either alone or in combination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416422 TI - Oxygen may improve dyspnea and endurance in patients with chronic obstructive pulmonary disease and only mild hypoxemia. AB - Oxygen (O2) has been reported to improve exercise tolerance in some patients with chronic obstructive pulmonary disease (COPD) despite only mild resting hypoxemia (PaO2 greater than 60 mm Hg). To confirm these prior studies and evaluate potential mechanisms of benefit, we measured dyspnea scores by numeric rating scale during cycle ergometry endurance testing and correlated the severity of dyspnea with right ventricular systolic pressure (RVSP) measured by Doppler echocardiography during a separate supine incremental exercise test. Both sets of exercise were performed according to a randomized double-blind crossover protocol in which patients breathed compressed air or 40% O2. We studied 12 patients with severe COPD (FEV1 0.89 +/- 0.09 L [mean +/- SEM], FEV1/FVC 37 +/- 2%, DLCO 9.8 +/ 1.5 ml/min/mm Hg[47% of predicted], PaO2 71 +/- 2.6 mm Hg). With endurance testing on compressed air, PaO2 did not change significantly in the group as whole (postexercise PaO2 63 +/- 5.1 mm Hg, p = NS), but did fall to less than 55 mm Hg in four patients from this group. Duration of exercise increased on 40% O2 from 10.3 +/- 1.6 to 14.2 +/- 1.5 min (p = 0.005), and the rise in dyspnea scores was delayed. Oxygen delayed the rise in RVSP with incremental exercise in all patients and lowered the mean RVSP at maximum exercise from 71 +/- 8 to 64 +/- 7 mm Hg (p less than 0.03). Improvement in duration of exercise correlated with decrease in dyspnea (r2 = 0.66, p = 0.001) but not with decreases in heart rate, minute ventilation, or RVSP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416421 TI - Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation. AB - Dyspnea, leg effort (Borg 0 to 10 scale), ventilation, and heart rate (VEmax/VEcap; HRmax/HRcap expressed as a percentage of capacity) were measured at maximal exercise (cycle ergometer) in 97 patients with chronic airflow limitation (CAL) (FEV, 46.6 +/- 14.23% of predicted) and compared with 320 matched control subjects. Patients with CAL achieved a maximum power output of 86 +/- 39.5 W (60 +/- 23.2% of predicted) compared with 140 +/- 37.5 W (98 +/- 14.5% of predicted) in controls (p less than 0.0001), VEmax/VEcap was 72 +/- 19.3% compared with 53 +/- 18.6% (p less than 0.0001), and HRmax/HRcap was 76 +/- 13.5% compared with 82 +/- 13% (p less than 0.001). These findings were expected. The median intensity of dyspnea was 6 (severe to very severe) and leg effort was 7 (very severe) in both groups, and these findings were unexpected. The patients with CAL were handicapped by an increase in both dyspnea and peripheral muscular effort relative to the actual power output. The rating of dyspnea exceeded leg effort in 25 (26%) of CAL versus 69 (22%) control subjects: the rating of leg effort exceeded dyspnea in 42 (43%) CAL and 117 (36%) control subjects; both were rated equally in 30 (31%) CAL and 134 (42%) control subjects, respectively (NS). VEmax/VEcap and HRmax/HRcap were not significantly different in those limited by dyspnea, leg fatigue, or a combination of both. All values are expressed +/- SD. PMID- 1416423 TI - Real-time gas analysis improves the measurement of single-breath diffusing capacity. AB - The measurement of single-breath diffusing capacity of the lung for carbon monoxide (DLCOsb) has traditionally used slow-responding analyzers that require large sample volumes for gas analysis. In addition, these measurement systems must use only assumed values of washout volume (Vwash) since gases are not measured continuously. More recently, a rapid analyzer was developed to continuously measure CO and methane (CH4, an inert tracer gas), which offers advantages, including accurate determination of Vwash and utilization of small sample volume (Vsamp) for gas analysis. We used this analyzer on 135 consecutive measurements of DLCOsb obtained from 70 patients and compared two analysis methods. (1) American Thoracic Society (ATS) guideline method: a standard Vwash (ATS-Vwash) of 0.75 L and a Vsamp of 0.75 L (for vital capacities [VC] less than 2.0 L, ATS-Vwash of 0.5 L and a Vsamp of 0.5 L); (2) VIS method: a Vwash visually just adequate to clear phases I and II of the CH4 washout curve (VIS-Vwash) and a Vsamp of 0.75 L (0.5 L for VC less than 2.0 L). We found that in four patients with VC less than 1.2 L, DLCOsb was attainable despite the small Vsamp (less than 500 ml). Of the other 66 patients whose tests were analyzed by both methods, 33 (50.0%) had Vis-Vwash less than or equal to ATS-Vwash such that phases I and II were actually cleared using ATS criteria. The other 33 patients (50.0%) had VIS Vwash greater than ATS-Vwash such that phases I and II could not be cleared using ATS criteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416425 TI - Effect of smoking cessation on pulmonary carbon monoxide diffusing capacity and capillary blood volume. AB - We studied 16 smokers, with a mean age of 41 yr (SD, 12 yr) and a mean DLCO of 81% predicted (SD, 19%), before and after smoking cessation. Two subjects were able to stop smoking for only 24 h, whereas 14 subjects abstained for 1 wk, 11 for 1 month, and five for 3 months. The initial mean DLCO in ml/min/mm Hg was 18.9 (SD, 4.6) after correction for COHb back pressure and the reduction in hemoglobin because of COHb. A week after smoking cessation there was a significant increase in DLCO, to 20.8 (SD, 5.4), p = 0.001. There was no further increase in DLCO at 1 month or at 3 months. In four subjects tested while they were still smoking and 24 h after smoking cessation, there was a significant increase in DLCO after correction for COHb, from 17.4 (SD, 1.5) to 19.8 (SD, 1.3), p = 0.02. These results indicate that after smoking cessation there is a rapid improvement in DLCO, suggesting that smoking had previously decreased DLCO. However, there may also be an irreversible component to the reduction of DLCO in some of the subjects in whom the DLCO remained abnormal even after continued smoking cessation for 1 month. PMID- 1416424 TI - Acute effect of cigarette smoking on the carbon monoxide diffusing capacity of the lung. AB - To determine the acute effect of smoking on DLCO, we studied 12 smokers (mean age, 36 yr; range, 19 to 52 yr, six men and six women) before and after they had smoked as many cigarettes as they could (mean, 6.0; SD, 1.9) over a period of 1 h. Blood COHb was estimated using a rebreathing-breathholding technique after a vital capacity inhalation of O2. Capillary blood volume (VC) was determined from DLCO performed at inspired O2 concentrations of 25 and 90%. DLCO (in ml/min/mm Hg) corrected for COHb back pressure decreased from 22.5 (SD, 6.6) before smoking to 21.0 (SD, 6.6) after smoking (p = 0.003). After correction for the "anemia effect" of COHb, DLCO still significantly decreased, from 22.8 (SD, 6.3) before smoking to 21.8 (SD, 6.4) after smoking p = 0.01). VC (corrected for the reduction in hemoglobin by COHb) was 52.0 (SD, 20.1) ml before smoking and 46.4 (SD, 22.7) ml after smoking; this difference did not achieve statistical significance (p = 0.056). There was no significant change in DLCO or VC in six control subjects tested before and after 1 h of sham smoking of an unlit cigarette. In 12 control subjects studied before and after inhalation of 0.1% CO to result in mean COHb levels of 10.6% (SD, 1.4%), there was a slight but significant decrease in VC (mean change, 21%) and in DLCO (mean change, 4%) after correction for COHb back pressure and reduction in available hemoglobin, suggesting that CO inhalation may have a direct effect on DLCO by reducing VC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416426 TI - Lung mechanics and gas exchange during pressure-control ventilation in dogs. Augmentation of CO2 elimination by an intratracheal catheter. AB - Increased awareness of pressure-related injury to the alveolar-capillary interface has renewed interest in modes of ventilation that limit alveolar distention such as pressure-controlled ventilation (PCV). We examined respiratory system mechanics and gas exchange during PCV in six dogs. Our data conformed to the predictions of our single-compartment mathematical model of respiratory dynamics during PCV (J Appl Physiol 1989; 67:1081-92). For a fixed pressure (Pset) and inspiratory time fraction (Tl/Ttot) (15 cm H2O and 0.3, respectively), minute ventilation (VE) reached a well-defined plateau as frequency (f) increased from 10 to 50 breaths/min and tidal volume (VT) fell progressively. Concomitantly, the physiologic dead-space fraction (VD/VT) increased from 0.50 +/ 0.04 to 0.85 +/- 0.04, and arterial PCO2 (PaCO2) rose from 39 +/- 4 to 76 +/- 12 mm Hg. At a fixed combination of frequency, applied pressure, and Tl/Ttot (40 breaths/min, 15 cm H2O, and 0.3), VE did not change when we introduced fresh gas continuously from an intratracheal catheter. However, PaCO2 and VD/VT fell progressively as catheter flow increased from zero to 14 L/min (60 +/- 12 to 40 +/- 12 mm Hg and 0.83 +/- 0.03 to 0.25 +/- 0.14 mm Hg, respectively). We conclude that during PCV at a fixed Pset and Tl/Ttot increasing frequency caused VT to fall and VE to reach a plateau. Declining VT was associated with a rise in PaCO2 because of a subsequent fall in alveolar ventilation. Insufflating fresh gas by an intratracheal catheter increased alveolar ventilation and improved CO2 elimination by washing out the anatomic dead space.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416427 TI - Use of the Blasius resistance formula to estimate the effective diameter of endotracheal tubes. AB - To early detect mucus deposition in endotracheal tubes (ETT), we propose using a geometric, flow-independent parameter, i.e., diameter of the ETT, based on a precise knowledge of ETT flow regime, instead of using the classic flow-dependent ETT resistance based on the empirical, nonlinear Rohrer equation. From the estimated slope of -0.24 derived from Moody diagrams characterizing the pressure flow relationship in ETT of various inner diameters (D), we first assessed that the Blasius resistance formula slope of -0.25 could be applied to adult-size ETT, meaning that flow remains fully developed, turbulent, and hydraulically smooth (0.5 L/s less than or equal to V less than or equal to 1.4 L/s). Insertion into the ETT of a pressure catheter (external diameter: d) to stimulate in vivo measurements did not modify these results, provided the hydraulic diameter, D* = D - d, was substituted for D in the Blasius formula. The Blasius formula was then used to determine, from in vitro pressure and flow measurements in ETT before intubation and in ETT lined with dry mucus secretions, the effective diameter, shown here to be highly correlated to the actual diameter measured by volumetric water displacement. The effective ETT diameter was measured in eight patients at different stages after oral or nasal intubation. Compared with the actual ETT diameter measured before insertion, the effective diameter was slightly reduced (2.6 +/- 2.5%) during the first week of intubation and was strongly reduced (12.2 +/- 2.8%) during the second week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416428 TI - Respiratory responses to chest compression in human subjects. AB - To test the hypothesis that respiratory compensation for chest compression in the conscious state is different from that in the unconscious state, a range of chest compression was applied to eight conscious and eight anesthetized subjects. Chest compression was carried out by inflating a pneumatic cuff inserted under a chest corset and placed over the anterior chest wall for 5 min. Cuff inflation pressures were 25, 50, and 100 mm Hg: light, moderate, and heavy chest compression, respectively. In both conscious and anesthetized subjects, chest compression immediately caused a decrease in tidal volume (VT) and a concomitant increase in respiratory frequency (f). These changes stabilized within 2 min and remained nearly steady for the rest of the sustained chest compression. The decrease in VT was more prominent the greater the loads, and the change in f was in reverse proportion to the change in VT. In conscious subjects the increase in f was due to shortening of both inspiratory time (T1) and expiratory time (TE), whereas in anesthetized subjects the increase in f was due solely to shortening of TE. In conscious subjects, the values of minute ventilation (VI) and end-tidal PCO2 (PETCO2) during light and moderate chest compression were not different from the control values, whereas VI increased and PETCO2 decreased during heavy chest compression. In anesthetized subjects, the values of VI and PETCO2 were not different from the control values at any different magnitudes of chest compression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416430 TI - Subpopulation of hyperresponsive polymorphonuclear neutrophils in patients with adult respiratory distress syndrome. Role of cytokine production. AB - To gain further insight into the pathogenesis of the adult respiratory distress syndrome (ARDS), we studied possible relationships among the activation status of circulating polymorphonuclear neutrophils (PMN), cytokine levels, and the severity of lung injury in 31 patients: 15 with ARDS, nine with severe pneumonia uncomplicated by ARDS, and seven mechanically ventilated with neither ARDS nor pneumonia. Nine healthy subjects served as controls. Using flow cytometry, we identified a subpopulation of PMN with an increased capacity to generate hydrogen peroxide after stimulation ex vivo in all three patient groups; significantly higher values were found in those with ARDS. The PMN stimulation index, a reflection of the degree of hyperresponsiveness, correlated with elevated levels of tumor necrosis factor-alpha (TNF alpha) in plasma, and both spontaneous and lipopolysaccharide-induced TNF alpha production by cultured monocytes. These biologic expressions of PMN activation and cytokine generation both correlated with indices of the severity of lung injury, but not with the overall clinical severity. In contrast, IL-6 and IL-1 beta showed little or no relationship with either the degree of lung injury or PMN hyperresponsiveness. We conclude that TNF alpha-primed PMN may play a major role in the pathogenesis of ARDS-associated lung injury. PMID- 1416429 TI - Increased serum catalase activity in septic patients with the adult respiratory distress syndrome. AB - Excessive hydrogen peroxide (H2O2) generation appears to contribute to the development of the adult respiratory distress syndrome (ARDS), but H2O2 combatting antioxidant defenses have not been evaluated. We found that serum from septic patients with ARDS scavenged more (p less than 0.05) H2O2 in vitro (82.7 +/- 3.8%) than did serum from septic patients without ARDS (56.9 +/- 3.1%) or control subjects (20.2 +/- 2.4%). Serum from septic patients with ARDS also had more (p less than 0.05) catalase activity (54.9 +/- 10.9 U/ml) than did serum from septic patients without ARDS (28.6 +/- 3.4 U/ml) or control subjects (7.3 +/ 0.8 U/ml). In contrast, serum from septic patients with or without ARDS and control subjects had the same glutathione peroxidase (GPX) activity. Serum H2O2 scavenging activity correlated with serum catalase (r = 0.77) but not GPX (r = 0.33) activity and was inhibitable (greater than 90%) by sodium azide, a catalase inhibitor. Increases in serum catalase activity did not appear to be derived from erythrocytes (RBC) because septic patients with or without ARDS and control subjects had similar RBC hemolysis in response to osmotic stress in vitro and serum haptoglobin concentrations. Serum from septic patients with ARDS also protected endothelial cells against H2O2-mediated damage (34.5 +/- 2.2% 51Cr release) better (p less than 0.05) than serum from septic patients without ARDS (47.3 +/- 7.4%) or control subjects (82.1 +/- 10.2%), but killing of bacteria by neutrophils in vitro was the same in serum from patients and control subjects. Our findings indicate that patients with sepsis and/or ARDS have increased serum catalase activity, which may alter H2O2-dependent processes. PMID- 1416432 TI - The clinical spectrum of lymphangiomas and lymphangiomatosis of the spleen. AB - Lymphangiomas of the spleen are infrequent neoplasms of the spleen with clinical manifestations ranging from insignificant incidental findings to large, symptomatic cystic masses requiring surgical intervention. An associated syndrome may be lymphangiomatosis, in which the lymphangiomatous process involves other sites or organs, such as the liver, spleen, axilla, and mediastinum. Vasoformative neoplasms (hemangioma, lymphangioma) are relatively uncommon tumors or hamartomas of the spleen. Although well reported in the literature, their surgical significance is not well recognized. These lesions present a broad spectrum of pathologic findings of varied surgical importance. As incidental findings, they may be mistakenly considered as a valid indication for splenectomy. On the contrary, more extensive involvement of the spleen may cause symptomatic splenomegaly, which is a valid indication for splenectomy. When the spleen is diffusely involved (lymphangiomatosis), it may be part of a syndrome of generalized lymphangiomatosis involving structures and organs other than the spleen. This syndrome should be considered in obscure cases of splenomegaly in which the usual hematologic causes have been ruled out. PMID- 1416431 TI - Effect of sulfidopeptide leukotriene receptor antagonists on endotoxin-induced pulmonary dysfunction in awake sheep. AB - We studied the effects of two structurally unrelated sulfidopeptide leukotriene receptor antagonists on endotoxin-induced pulmonary dysfunction in chronically instrumented unanesthetized sheep. The agents employed were L-660,711 (MK-571) (Merck-Frosst, Canada) and SK&F 104,353 (Smith Kline and French, King of Prussia, PA). The efficacy and specificity of the agents were verified in sheep by administering boluses of exogenous leukotrienes (LTB4, LTC4, LTD4, and LTE4) in doses as great as 100 micrograms while monitoring lung mechanics and vascular pressures. The antagonists blocked the changes in lung mechanics and pulmonary hemodynamics induced by the sulfidopeptide leukotrienes (LTC4, LTD4, and LTE4) while having no effect on the animals' responses to LTB4. The endotoxin studies were performed by administering endotoxin alone (Escherichia coli endotoxin 0.75 microgram/kg) or endotoxin after pretreatment with one of the sulfidopeptide leukotriene receptor antagonists. In control studies, each animal received a continuous infusion of one of the receptor antagonists for a duration identical to that of the endotoxin studies. Neither L-660,711 nor SK&F 104,353 significantly altered the endotoxin-induced changes in pulmonary hemodynamics, lung mechanics, lung fluid and solute exchange, oxygenation, or leukopenia. Peak lung lymph thromboxane B2 levels were significantly lower in sheep pretreated with L-660,711. When the antagonists were given alone, no effects were seen. We conclude that (1) sulfidopeptide leukotrienes do not measurably contribute to endotoxin-induced pulmonary dysfunction in chronically instrumented sheep; (2) sulfidopeptide leukotrienes may contribute to thromboxane release after endotoxin. PMID- 1416433 TI - Colonic diverticular disease in patients 40 years old or younger. AB - Diverticular disease in patients 40 years of age or younger has been described as rare but virulent. Previous studies, based on age, on diverticular disease are often confusing because of inexact definitions of the disease status. With these criticisms in mind, the authors studied 322 clinical records on patients admitted with a diagnosis of colonic diverticulosis or diverticulitis to the University of New Mexico Hospital and the Lovelace Medical Center. Of these patients, 285 had documented evidence of colonic diverticula with only 6 per cent of these being 40 years of age or younger. The criteria for acute diverticulitis were met by 86 patients, 17 of whom were 40 years of age or younger. The younger group had disproportionately more men, particularly Hispanics. The authors conclude that acute diverticulitis is more common in the young than suggested by previous reports, but the behavior of the disease is not distinctive. PMID- 1416434 TI - Massive gastrointestinal hemorrhage in pancreatitis secondary to visceral artery aneurysms. AB - Thirty-six pancreatic patients with massive gastrointestinal bleeding have now been identified as having pancreaticoduodenal and gastroduodenal artery aneurysms as causative. In the past decade, seven of the patients have been encountered at the authors' institution and seven presented in the literature. Of these 14, there was a predilection for men (85%) with an average age of 48.1 years, who had complications of pancreatitis (75%), that is, abscess or pseudocyst. Eleven of these patients underwent surgery with an 81 per cent survival rate. Previous reports had shown a 47 per cent survival rate in 19 similar patients. Embolization of the aneurysm was attempted in four patients with two successes. The authors believe that early diagnosis by arteriography and early operative intervention were responsible for the improved survival. A high index of suspicion in this patient population is crucial for early diagnosis and improvement in survival. PMID- 1416435 TI - Abdominal vascular trauma: a review of 106 injuries. AB - A retrospective analysis of acute abdominal vascular injuries was performed to review outcome variables and treatment principles. The authors review their most recent 5-year experience with 106 major abdominal vascular injuries in 64 patients treated at a combined Army and Air Force urban medical center. The majority of the patients were young men who sustained penetrating injuries. There were 41 (64%) gunshot wounds, 17 (27%) stab wounds, and 6 (9%) sustained blunt trauma. Forty-five patients (71%) came to the hospital in shock. The inferior vena cava in 26 patients (41%) and the aorta in 11 patients (17%) were injured most frequently. Suture repair was possible in 53 (50%) injuries. Ligation was performed in 41 (39%). Overall mortality for the series was 39 per cent. Hemorrhagic shock was the cause of death in 23 patients (92%) with only two late deaths. Transfusion requirement, presence of shock, and number of vessels injured all affected outcome. Immediate stabilization in the emergency department includes appropriate crystalloid and blood product resuscitation with minimal delay for diagnostic studies. Prompt abdominal exploration to control hemorrhage and particular attention to factors associated with coagulopathy remain the key elements in saving the lives of these severely injured patients. PMID- 1416436 TI - The role of laparoscopy in the diagnosis of acute appendicitis. AB - Patients with acute appendicitis who present with an atypical clinical picture are frequently subjected to a series of laboratory and x ray tests and sometimes to prolonged observation before surgery. There is a significant number of normal appendixes found at laparotomy, particularly in some subgroups of patients such as the immunocompromised, the elderly, and the young woman. Laparoscopy was done in 38 patients with right lower quadrant pain of undetermined cause after extensive diagnostic efforts. This group of patients included men and women with an even distribution of ages between 20 and 78 years. Laparoscopy was done under local anesthesia to better establish the site of pain if no obvious pathology could be visualized. Acute appendicitis was confirmed in only 26.3 per cent of the cases, and a wide variety of nonappendiceal diseases were identified, the majority of them requiring no surgery. Diagnostic laparoscopy performed under local anesthesia should be considered in patients suspected to have acute appendicitis, regardless of age and sex, who present with an atypical picture and who still offer diagnostic doubts after other available conventional tests. PMID- 1416437 TI - Primary lymphoma of the rectum. AB - Primary lymphoma of the rectum is rare. Its usual grouping with primary lymphoma of the gastrointestinal tract leaves little in the literature that deals specifically with a primary rectal lymphoma. Various treatments have been reported ranging from abdominoperineal resection with adjuvant chemotherapy and radiation therapy to chemotherapy or radiation therapy alone. A case of primary rectal lymphoma is presented and the literature is reviewed. In the few cases reported in the literature, patients treated surgically had a better prognosis than those treated nonsurgically with an overall 5-year survival of 50 per cent. Recommended treatment includes varying forms of surgical therapy ranging from local resection to abdominoperineal resection. Adjuvant chemotherapy, radiation therapy, or both should be considered. PMID- 1416438 TI - Ileocolonic anastomosis: a comparison of the patency of stapled versus hand-sewn techniques. AB - This study compared strength of hand-sewn sutures to that of staples for end-to end anastomoses of ileocolostomies in 20 mongrel dogs. In ten dogs, the authors used four applications of staples for the anastomoses. In the other ten, they performed single-layer anastomoses using 4-0 polypropylene sutures. Half the dogs were sacrificed on the third postoperative day; half were sacrificed on the fifth postoperative day. Bursting strengths were obtained by infusing air through a catheter inserted into the colon. Results showed the single-layer hand-sewn anastomosis was significantly stronger than the stapled anastomosis. In addition, a histologic comparison of the two closures showed no difference in inflammatory responses. PMID- 1416440 TI - Resident education in surgical endoscopy. AB - Under the auspices of the Resident Education Committee of the Society of American Gastrointestinal Endoscopic Surgeons, 158 of 298 (53%) of surgical training program directors responded to a survey on the current status of endoscopy in residency programs. Although 100 per cent claim that gastrointestinal endoscopy is provided by their program, only 76 per cent have formal endoscopy training, usually centered around the PGY 3 level, with only 23 per cent having didactic lectures in endoscopy. Directors claim to have trained nearly all of their residents by the completion of residency, averaging 44 esophagogastroscopies, 37 colonoscopies, and 46 flexible sigmoidoscopies per resident. However, they feel only 71 per cent of trainees are able to perform esophagogastroscopies and 67 per cent to perform colonoscopies in clinical practice. Ninety-seven per cent of directors feel endoscopy is important to surgical residency training, and 87 per cent have full-time faculty doing endoscopy. Only 44 per cent have a director of endoscopy; endoscopy is supervised by surgeons exclusively in only 48 per cent. Only 35 per cent have ongoing endoscopy research. When surgeons are not performing endoscopy, 66 per cent feel that the gastrointestinal (GI) service provides adequate service or training. Gastroenterology has a monopoly in endoscopy at 28 per cent of institutions, and 67 per cent of program directors feel there would be resistance to the formation of a separate surgical endoscopy service. Surgeons work in their own surgical endoscopy suite in only 15 per cent of institutions; in a GI suite in 13 per cent; and in a combined suite in the remainder.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416439 TI - An unusual complication of laparoscopic cholecystectomy. AB - An unusual series of complications of laparoscopic cholecystectomy is presented. The complications occurred after use of laparoscopic technique in the treatment of acute cholecystitis. The authors feel that this is a problem that points up the need for experience and caution in the use of laparoscopic cholecystectomy in the setting of acute cholecystitis. PMID- 1416441 TI - The effect of proximal gastric vagotomy plus duodenoplasty on duodenogastric reflux. AB - Alkaline reflux gastritis is a clinical syndrome that results from a mucosal injury by duodenal contents. In this study, the amount of duodenogastric reflux was assessed in patients who previously underwent proximal gastric vagotomy (PGV group; n = 11) and PGV plus duodenoplasty (PGV+D group; n = 10) as a treatment for duodenal ulcer. The control group (A) consisted of 11 healthy volunteers without endoscopic abnormalities. A quantitative index of duodenogastric reflux was obtained in each case by determining the percentage of the injected dose of 99mTechnetium-DISIDA that was recovered by continuous aspiration of gastric juice in fasting subjects. In the PGV group, the percentage of administered 99mTechnetium-DISIDA recovered from the stomach (median: 0.69%; range: 0.09% 3.61%) did not differ significantly (P > 0.05) from that of the PGV+D group (median: 0.49%; range: 0.09%-3.91%) and from that of the A group (median: 1.47%; range: 0.22%-3.01%). The results show that proximal gastric vagotomy plus duodenoplasty did not increase duodenogastric reflux. PMID- 1416442 TI - Orthotopic liver transplantation with abdominal situs inversus and dextrocardia. AB - Anatomic anomalies may present technical difficulties during orthotopic liver transplantation. Abdominal situs inversus was considered a contraindication to liver transplantation. A successful liver transplant in a patient with both situs inversus and dextrocardia is described, along with a technical review. PMID- 1416443 TI - Cost containment in the operating room: use of reusable versus disposable clothing. AB - The need for fiscal austerity has prompted the re-evaluation of many aspects of medical care. Recent events in the northeastern United States have caused an increased awareness of the need for environmental responsibility as well. With these considerations in mind, the costs incurred by the operating suites of two comparable teaching hospitals in New Jersey, one of which uses disposable operating room attire, were examined; the other employs reusable scrub suits and gowns. The reusable scrub suits and gowns resulted in a savings in excess of $100,000 compared to the center using disposables. The authors conclude that hospitals should re-evaluate their use of disposable operating room attire to reduce operating costs and the amount of medical waste generated. PMID- 1416444 TI - Endoscopic papillotomy while the gallbladder is in situ. AB - The authors report on their experience with 25 patients who underwent an endoscopic papillotomy with gallbladder in situ and review the current literature on this topic. Twenty-four out of 25 patients in this study had their common bile duct cleared of stones. Five patients (24%) required cholecystectomy on follow-up at an average of 14.4 months. There was no mortality associated with the procedure. The authors' experience and review of the literature suggest that endoscopic papillotomy plays an important role in the removal of common bile duct stones in persons who have their gallbladder in situ, especially in those patients who are at high risk for surgery, either because of advanced age or other medical problems. However, the use of endoscopic papillotomy alone in young, healthy persons is more problematic because of the relatively high rate of cholecystitis or recurrent biliary colic necessitating a cholecystectomy at a later date. The authors suggest that, in the future, the ideal treatment regimen for common bile duct stones in patients with their gallbladder in situ may be urgent endoscopic papillotomy with a scheduled elective laparoscopic cholecystectomy. PMID- 1416445 TI - [Nutrition and sports in adolescence]. PMID- 1416446 TI - [Sociocultural determinants of feeding behavior in adolescents]. PMID- 1416447 TI - [Background of pediatric education and current situation]. PMID- 1416448 TI - [Perspectives of pediatric education]. PMID- 1416449 TI - [Teaching pediatrics at the undergraduate level]. PMID- 1416450 TI - [Teaching general pediatrics]. PMID- 1416451 TI - [Pediatrics education]. PMID- 1416452 TI - [Prenatal diagnosis and treatment of congenital adrenal gland hyperplasia]. PMID- 1416453 TI - [Indications and surgical techniques in intersexual states]. PMID- 1416454 TI - [The test of exhaled H2]. PMID- 1416455 TI - [Intestinal permeability]. PMID- 1416456 TI - [Diagnostic imaging in gastroenterology]. PMID- 1416457 TI - [Therapeutic advances in infantile asthma. Introduction]. PMID- 1416458 TI - [Hepatic transplantation in children. Postoperative management and early complications. Experience at the Vall d'Hebron Children's Clinic of Barcelona. 1992]. PMID- 1416459 TI - [Inhalation++ steroids in the treatment of infantile asthma]. PMID- 1416460 TI - [Generalized bacterial infection in the newborn. Introduction]. PMID- 1416461 TI - [Generalized bacterial infection in the newborn. Diagnosis: early markers of infection]. PMID- 1416463 TI - [Adjuvant therapy in neonatal sepsis]. PMID- 1416462 TI - [Antibiotic therapy in the neonatal period]. PMID- 1416464 TI - [Generalized bacterial infection in the newborn. Prognosis and sequelae]. PMID- 1416465 TI - [The most frequent complications in the postoperative period of hepatic transplantation at the pediatric intensive care unit]. PMID- 1416466 TI - [Cognitive and affective changes in the epileptic child. Introduction]. PMID- 1416467 TI - [Inter-crisis cognitive-behavioral disorders in epilepsy in children]. PMID- 1416468 TI - [Affective problems in the epileptic child and his environment]. PMID- 1416469 TI - [School and work performance in the epileptic child]. PMID- 1416470 TI - [Antiepileptic drugs and cognitive function]. PMID- 1416471 TI - [Brain tumors in childhood. Introduction]. PMID- 1416472 TI - [Early diagnosis of brain tumors in childhood]. PMID- 1416473 TI - [Brain tumors in childhood. Diagnosis with the new imaging methods]. PMID- 1416474 TI - [The new surgery]. PMID- 1416475 TI - [Chemotherapy in infantile brain tumors]. PMID- 1416476 TI - [Acute otitis media. Etiopathogenesis]. PMID- 1416477 TI - [Infective complications in children with bone marrow transplantation]. PMID- 1416478 TI - [Clinical course and diagnosis of the exudative forms]. PMID- 1416479 TI - [Acute otitis media in 1992]. PMID- 1416480 TI - [Otitis media. Surgical treatment]. PMID- 1416481 TI - [Child abuse: current approaches in investigation and intervention. Introduction]. PMID- 1416482 TI - [Update on investigation on child abuse in Spain]. PMID- 1416483 TI - [Renal transplant in children: postoperative management]. PMID- 1416484 TI - [Detection as part of intervention]. PMID- 1416485 TI - [Intervention on the abusing family itself]. PMID- 1416486 TI - [The development of professional associations in cases of child abuse]. PMID- 1416487 TI - [Prophylaxis and prevention of infection in children with a transplant]. PMID- 1416488 TI - [Up-date on intervention radiology in pediatrics. Introduction]. PMID- 1416489 TI - [Shockwave lithotripsy in children]. PMID- 1416490 TI - [Immunotherapy: concept and indications]. PMID- 1416491 TI - [Immunologic mechanisms of immunotherapy]. PMID- 1416492 TI - [Forms of immunotherapy. Various routes of administration]. PMID- 1416493 TI - [Immunotherapy in infantile allergy. Follow-up and control. Results. Criteria for discontinuation]. PMID- 1416494 TI - [Anxiety disorders in childhood and adolescence. Conceptual and psychopathologic introduction]. PMID- 1416495 TI - [Anxiety and depression]. PMID- 1416496 TI - [Nutritional needs in adolescence. Risk factors]. PMID- 1416497 TI - [Nutrition in pregnancy in adolescence]. PMID- 1416498 TI - [Iron deficiency during adolescence]. PMID- 1416499 TI - [Nutrition in anorexia nervosa]. PMID- 1416500 TI - [Treatment of Turner syndrome]. PMID- 1416501 TI - [Growth retardation of intrauterine origin]. PMID- 1416502 TI - [Growth retardation of skeletal origin: with special reference to osteochondrodysplasias]. PMID- 1416503 TI - [Therapeutic implications of growth hormone in infancy and childhood]. PMID- 1416504 TI - [Surgical possibilities for treatment of short stature]. PMID- 1416505 TI - [Growth deficiency: concept and classification]. PMID- 1416506 TI - [Growth deficiency: dignostic methodology]. PMID- 1416507 TI - [Advances in growth]. PMID- 1416508 TI - [Genetic disorders and growth hormone]. PMID- 1416509 TI - [Growth, growth hormone and puberty]. PMID- 1416510 TI - [Human placental growth hormone]. PMID- 1416511 TI - [Growth and chronic diseases]. PMID- 1416512 TI - [The pattern of human growth. Factors conditioning and regulating growth]. PMID- 1416513 TI - [Hormonal regulation of growth during pubertal development: effect of sex hormones]. PMID- 1416514 TI - [Progressive myoclonic epilepsy in childhood and adolescence]. PMID- 1416515 TI - [Differentiated thyroid carcinoma in childhood]. AB - We report the cases of 6 patients, all younger than 14 years of age, with differentiated thyroid carcinoma. None of the patients had a previous history of radiation exposure. All patients presented with an enlarged thyroid gland as a solitary nodule, with or without cervical nodes. The fine-needle aspiration cytological examination was found to be the most sensitive and specific, evidencing 5 pure papillary adenocarcinoma and 1 follicular. Our standard preoperative evaluation included thyroid scintiscan and ultrasound examination, laboratory studies of thyroid function and serum calcitonin, chest x-ray, fine needle aspiration and vocal cord examination. The treatment was total thyroidectomy and bilateral modified neck dissection. A whole body scan (WBS) with 131I was performed 6 weeks after surgery, followed by radioiodine therapy for ablation of thyroid remnants and treatment of metastases when present. Patients then began thyroid replacement treatment. The follow-up of the patients consisted of thyroglobulin and WBS. The microscopic carcinoma was found in the contralateral lobe in 100%. Lung metastases were detected in 2 patients. All of the patients have survived during a follow-up period ranging from 6 to 108 months. PMID- 1416516 TI - [Marfan syndrome in childhood: cardiovascular manifestations. Echocardiographic changes]. AB - We report the cases of eight children with Marfan syndrome. Seven (87.5%) were diagnosed with cardiopathy, everyone with auscultatory findings. Electrocardiographic patterns were nonspecific. Enlargement of the aortic root was present in two of the cases as seen by thorax x-rays. Echocardiography detected the presence of mitral valve prolapse in 87.5% of the patients (7 cases) and aortic enlargement in 75% of the patients (6 cases). Echocardiography also detected the presence of aortic dysplasia, tricuspid valve prolapse and right and left ventricular hypertrophy. During the follow-up period, no case had cardiac failure. There was no mortality. The aortic enlargement was progressive and was not modified by propranolol treatment. Surgical treatment was not needed. Family history related to this condition was present in a very small percentage (37.5%). We comment on one infantile form of Marfan syndrome with its own phenotype different from that of classical Marfan syndrome. PMID- 1416517 TI - [Evaluation of the western blot test in the follow up of children born to HIV seropositive mothers]. AB - We have made a follow-up study of 65 children born to HIV seropositive mothers. These children were studied during the first quarter of life and subsequently every three months thereafter to measure the usefulness of the Western Blot technique in the detection of the gradual development of seroreversion, as well as in HIV infection. The study of 25 mother-child pairs allowed us to anticipate seroreversion up to three months, showing an earlier and quicker finding than by indirect immunofluorescence. In the HIV diagnosis during the first 15 months of life, the sequential study of serum by Western Blot is able to detect the reappearance of new bands, indicating the endogenous production of antibodies in the child. The circunstance is observed in 7 out of 10 infected children, showing the reappearance of bands corresponding to antibodies against p-31 and/or p-55 proteins between the second and fourth quarter of life. PMID- 1416519 TI - [Attempted suicide in childhood and adolescence: epidemiologic characteristics]. AB - Suicide attempts among children and adolescents are occurring more frequently in the last years. In fact, in some countries suicide is the third leading cause of death for adolescents between 15 and 19 years of age, in spite of the fact that it is probably significantly underreported. The present study aimed at examining the factors related to suicide attempts in thirty children and adolescents between 6 and 16 years old. These patients were compared to a randomly selected control group. A systematic review of the patients' charts was performed. We found that suicide attempts increased with age, 83% of those patients attempting suicide were female, the medical lethality of the means used in the attempt did not correlate with the patient's perception of the risk of dying, and recent stressful life events could often be identified as precipitators for attempting suicide. PMID- 1416518 TI - [Anemia and depletion of iron reserves in healthy 12-month-old infants]. AB - A prospective study was made which included 287 infants, 12 months of age and patients of two Vizcaya Health Centers, in order to determine the prevalence of anemia and/or depletion of iron stores. The study design included somatometry and a review of the clinical records, dietary habits and the socio-economic status of the family. Laboratory tests included: hematocrit, hemoglobin, mean corpuscular volume, number of erythrocytes, serum iron, transferrin, iron saturation percentage and serum ferritin. Anemia was present in 9.3% of these children and 6.9% had iron-deficiency anemia. Depletion of iron stores was found in 12.4%. Prematurity, socio-economic status, infants fed low-iron milk, early introduction of cow's milk and the weight at 12 months were all variables that correlated significantly with the anemic or iron deficient states. However, the number of infections during the first year of life did not show a significant correlation. A question about the necessity of routine screening is raised and recommendation is made for iron supplementation in the infants in the high risk group. PMID- 1416520 TI - [Neurologic alert signals in one-year-old infants: relation to signs of intrapartum hypoxia]. AB - As a method to evaluate the neurologic evolution and to establish if there exists any differences in the relation with the signs of intrapartum hypoxia, we have explored the neurologic "alert signs" at a certain age (12 months of life) in 80 full-term newborn infants with normal weight and without criteria of neurologic risk. We did not find statistically significant differences in the presence of alert signs in regards to sex, gestational risk, type of amniotic fluid, way of delivery, one-minute and five-minute Apgar scores or acid-base state in the umbilical artery at birth. We did find a significant increase in the number of alert signs in patients with cardiotocographic patterns that were suspicious or not tranquil in relation to those whose cardiotocographic patterns were tranquil. PMID- 1416522 TI - [Fibro-bronchoscopy without general anesthesia in pediatric patients]. AB - Flexible bronchofiberoscopy is at present an indispensable technique in pediatric pulmonology departments. The fact that it can be used outside of the operating theater without general anesthesia or additional oxygen has greatly increased its field of pediatric applications. Thirty-three fibrobronchioscopies were performed during a period of one year on a group of children under 14 years of age. The most common indications for the procedure were atelectasis (27.3%), recurrent pneumonia (15.1%) and a possible foreign body (15.1%). The most usual sedation (82%) was the combination of Diazepan with Ketamine. Sixteen patients did not require oxygen and only one suffered a serious complication. The benefit of this technique was shown since the treatment of 22 children (67%) was changed following this procedure. PMID- 1416521 TI - [Type 1 diabetes mellitus and nephropathy. Predicting factors in pediatric age]. AB - OBJECTIVE: To find the existence of early relationships between alterations in the glucidic metabolism and the glomerular and tubular basal function in diabetic insulin-dependent children without clinical evidence of diabetic nephropathy (DN). METHODS: We determined blood pressure, basal plasma concentrations of glucose, glycosilated hemoglobin and total proteins, glomerular filtration rate (GFR), and the glucose, proteins, calcium, phosphorus, uric acid, sodium, potassium and chloride excretions in diurnal, nocturnal and 24-hour urine samples in 43 diabetic children and 13 healthy controls. RESULTS: The microproteinuria mean value in all urine samples (always less than 15 micrograms/min/1.73 m.2), the GFR and blood pressure were similar in both groups. In the diabetic children, we found an inverse correlation between age and 24-hour urine microproteinuria (r 0.33; p less than 0.05) and between age and nocturnal urine microproteinuria (r 0.35; p less than 0.05). There was also a highly significant correlation between microproteinuria and the albumin/creatinine ratio in urine samples (r = 0.94, p less than 0.0001). Diabetic children showed a greater nocturnal excretion of calcium (p less than 0.05) and phosphorus (p less than 0.05). CONCLUSIONS: Our results suggest that microproteinuria, GFR and blood pressure have not served as predictors of DN in pediatric patients. PMID- 1416524 TI - [Hyperapo-beta-emia in children. Study of 17 families]. AB - Apolipoprotein (apo)-beta is an atherosclerotic risk factor in adults and children. In families with Familial Combined Hyperlipidemia (FCH) it has been described as a lipoprotein phenotype called Hyperapobetalipoproteinemia (Hyperapo beta) and characterized by increased numbers of small, dense and apo-beta enriched low density lipoproteins. In our Lipids Clinic, we have studied 267 children, but for the purpose of this paper we have only taken into account the 19 of these children who showed increased plasma total apo-beta levels (Hyperapo beta-emina). To investigate the type of dyslipoproteinemia of these children, we divided them into two groups: 1) Group 1: 10 children with apo-beta levels greater than mean + 2 standard deviations (SD); 2) Group 2: 9 children with apo beta levels greater than mean + 3 SD. We have also studied the fathers, mothers, brothers and sisters of all the children. Only one child (Group 1) had type IIb hyperlipoproteinemia. The other children had type IIa hyperlipoproteinemia. In each group, 4 families had FCH and the others had either Familial Hypercholesterolemia or Polygenic Hypercholesterolemia. Families with FCH could also have hyperapo-beta. It is possible that in the future some children of FCH families and those with type IIa hyperlipoproteinemia will have increased plasma triglyceride levels. This could be prevented by a proper diet. PMID- 1416523 TI - [Recurrent familial amyotrophic neuralgia of the brachial plexus. Report of a family and review of the literature]. AB - A family with hereditary neuralgic amyotrophy of the brachial plexus throughout three generations is described. Outstanding features are early onset occurring during childhood or adolescence, unlike the idiopatic sporadic form of the disease, and the association with a peculiar physiognomy that reminds one of the facial expression found in Modigliani's paintings. Clinical evolution is not always favorable since relapses and long-lasting sequelae are common. The disease is inherited through an autosomal dominant gene with high penetrance and the neuropathy is always associated with the phenotypic features. The possible relationship with other pathological entities of very different clinical expression, such as tomacular neuropathy, is discussed, as well as the distinguishing peculiarities between the inherited and the sporadic forms of brachial plexus neuropathy. PMID- 1416525 TI - [Association of neurofibromatosis type 1 and medulloblastoma]. PMID- 1416526 TI - [Chronic recurrent multifocal osteomyelitis. Presentation of a case]. PMID- 1416527 TI - [Intracardiac mycetoma induced by central catheterization]. AB - We report a case of an infective endocarditis presented as a right atrial mass which pathological study showed a big vegetation of candida albicans (mycetoma). We think its presence was related to a great central vein catheterization during the neonatal period. The clinical feature was completed with pulmonary fungal embolism and later tricuspid valve afectation. With this work we wish to remark the necessary careful management of patients with central vein catheters to avoid this severe complication. We review the pharmacological and surgical treatment of this uncommon entity. PMID- 1416528 TI - [Lymphoid polyp of cecal localization]. PMID- 1416529 TI - [Apropos of milk formulas]. PMID- 1416530 TI - [Cardiac rhabdomyoma in neonates and infants]. PMID- 1416531 TI - [Aneurysmal dilatation of the portal system. Apropos of a case diagnosed in a newborn infant]. PMID- 1416532 TI - [HIV infection in infants under 15 months of age. Value of the p-24 antigen as a prognostic marker]. AB - We have studied 65 children, born to HIV seropositive mothers, during the first quarter of life and afterwards every three-months. During this time, ten of the children (13%) became infected with the virus. The study of p24 antigen during the first 15 months of life showed an inverse relationship between the permanent presence of P24 antigen in the serum and the absence of anti-p24 antibodies. Since both markers were related to a bad prognosis, it is useful to carry-out the routine study of p24 antigen and its level in serum. Of the infections detected, 3 cases were early onset and the other 7 cases later onset. The three children from the first group died between 4 and 8 months of life, while the second group had a much more stable clinical situation. The children with early onset infections had T4 lymphocytes lower than 500 cell/mm3, detectable p24 antigen, and a fatal progression of the disease. PMID- 1416533 TI - [Evaluation of the bone mass by dual-photon absorptiometry in children under prolonged anticonvulsant therapy]. AB - We have evaluated, in a prospective study, the total and per unit area mass, measured in lumbar spine by Dual Photo-absorptiometry, in a group of 62 children on long-term anticonvulsant treatment. A second group of 58 normal children was used as a control. The total and per unit area bone mass increased with age, weight, height and bone maturity in all of the children studied. There were no significant differences found between the two groups. Children on multi-therapy and that were over six years of age showed statistically significantly less bone mass per area when compared th the control group (p less than 0.01). Phenobarbital, Carbamazepine and Valproic acid in monotherapy did not statistically diminish bone mass. Of these anticonvulsants, Phenobarbital was responsible for the most statistically significant decline in bone mass per area (p = 0.027). After six year of treatment, whether on mono-therapy or on poly therapy, bone mass was lower with respect to the control series, although this was not statistically significant. PMID- 1416534 TI - [The limit of pediatric age in primary health care. A problem to be solved]. AB - The true definition of the term Pediatrics, implies comprehensive care up to the end of adolescence; in practice, however, treatment is usually only available up to the age of seven. In this study, the medical records of children born between 1976 and 1983 were examined with respect to the four areas of General Practice covered by a pediatrician. The characteristics of this conurbation and the nature of medical advice sought were also studied. A survey of the situation in the remainder of the country was also carried out by means of telephone conversations with pediatricians nationwide. Of the 519 children considered, 150 did not consult their doctor during 1990. Those that did seek medical attention did so on 802 occasions, which represents 3.6% of all consultations by general practitioners. However, it would have amounted to 25.3% of the visits to pediatricians. Raising the age limit of pediatric patients, as an isolated measure, would therefore overload pediatric offices and thus lead to a lower standard of medical care. Such a measure should not be implemented hastily. PMID- 1416535 TI - [Pancreatic echography in infantile diabetes]. AB - Our objective was to investigate the pancreatic ultrasonographic size in diabetic children in order to compare in with a healthy population of children and to relate it to the characteristics of their disease. Fifty-four children (age 8.59 +/- 3.38 years) with insulin-dependent diabetes mellitus of short evolution and 23 healthy children of similar ages and sex were investigated. Anteroposterior measurement of pancreatic head, body and tail with real time ultrasonography were performed searching for a relationship of these factors with the acinar and residual insular function. The pancreatic measurements in the diabetic patients were sizeable smaller than in the healthy children with no relationship to age, height, weight or body surface. There were no differences in the pancreatic measurements in relationship to the evolution time or residual insular function in the diabetics. PMID- 1416536 TI - [Results of a study of the presence of spontaneous otoacoustic emissions in the newborn]. AB - An otoacoustic emission is that part of sound that can be detected in the ear canal and is produced by the physiological cochlear activity involved in the auditive process. Some people have spontaneous oto-emissions (SOAE), which are emissions that can be registered without any stimulus. These are normal functional sounds of some cochleae. he aim of this study was to assess the presence of SOAE in newborns, as well as to study its incidence and relationship with the auditive process. The number of tested neonated was 364, 209 of whom had at least one ear with SOAE+ (57.4%). It was possible to do a bilateral test in only 324 newborns, 114 of whom had SOAE+ in both ears (35.18%). The total number of ears tested was 961 and in 453 of these a SOAE+ was detected (47.1%). This high incidence of SOAE corresponds to a very good cochlear condition compared to that of older people. PMID- 1416537 TI - [Acute otitis media in childhood. Clinical and microbiological study of 50 cases]. AB - Fifty cases of acute otitis media effusion (AOME) in children less than 14 years of age are reported. The largest age group consisted of children less than 22 months of age (22 cases). Otolgia or irritability (80%) and fever (66%) were the most common symptoms. Tympanocentesis of the middle-ear effusion was performed in all of the cases. Haemophilus influenzae was recovered in 13 patients (26%), S. pneumoniae in 12 (24%), S. pyogenes in 4 (8%), P. aeruginosa in 2 (4%), anaerobic bacteria in 2 (4%) and mixed cultures in 4 children; 2 cases of H. influenzae and S. pneumoniae, 1 case of S. pneumoniae and E. coli, and 1 case of E. coli and P. aeruginosa. There were no cases of M. catarrhalis or S. aureus. We conclude that H. influenzae and S. pneumoniae are the most frequent pathogens (60% of all patients and 81% of the positive cultures). PMID- 1416538 TI - [Neurologic changes or vertebral malformations in children with anorectal malformations]. AB - We present a prospective study of 40 patients with anorectal malformations. We have studied the correlation between neurological impairment and vertebral anomalies. We did not find a statistical correlation. PMID- 1416539 TI - [Congenital syphilis and syphilitic mothers. Survey of the past 10 years]. AB - Two hundred and sixty-two newborn infants, born to mothers with a positive syphilis serology, have been studied. Twenty-six newborn infants had congenital syphilis and two hundred and thirty-six were considered as newborn infants from syphilitic mothers. This study has demonstrated that the newborn infants with congenital syphilis have been born to mothers with greatest risk factors. Newborn infants with congenital syphilis born to mothers on treatment during the pregnancy had a milder case of congenital syphilis than newborn infants born to mothers without treatment during the pregnancy. A diagnostic test for the treatment in these newborns has been proposed; if the test score is less than 5, we are dealing with a child of a syphilitic mother that does not need treatment and if the test results are higher than 5 we can confirm the diagnosis of congenital syphilis and immediate treatment must be started. PMID- 1416540 TI - [Five cases of Goldenhar-Gorlin syndrome]. AB - Five patients with Goldenhar-Gorlin's syndrome (facio-auriculo-vertebral dysplasia) are presented in this study. Their clinical characteristics are commented on along with an illustrative iconography. The literature on this subject has been reviewed and we make some comments on the possible ethiopathogeny of this disease. PMID- 1416541 TI - [Idiopathic 2nd degree type I atrioventricular block in an infant]. PMID- 1416542 TI - [Neonatal lupus erythematosus: dermatitis, A-V block and SSA/Ro antibodies]. PMID- 1416543 TI - [MULIBREY (MUscle, LIver, BRain, EYe) nanism. Report of a new case]. PMID- 1416544 TI - [Spontaneous resolution of cholelithiasis associated with cholestasis in an infant]. PMID- 1416545 TI - [Membranous laryngo-tracheo-bronchitis associated with infectious mononucleosis]. PMID- 1416546 TI - [Portal atresia. Clinico-pathological study of a case]. PMID- 1416547 TI - [Campomelic dysplasia: apropos of a case]. PMID- 1416548 TI - [Mesenteric cysts]. PMID- 1416549 TI - [Neonatal cystic neuroblastoma]. PMID- 1416550 TI - [Congenital generalized lipodystrophy]. PMID- 1416551 TI - [Ambliopia in pediatric age]. PMID- 1416552 TI - [Wolff-Parkinson-White disease in childhood: follow up of 36 cases]. AB - We have studied 36 patients (19 females and 17 males), controlled between 1973 and 1989, who suffered Wolff-Parkinson-White (WPW) pattern in their electrocardiogram. Epidemiological, clinical, diagnostic, therapeutic and evolutional data were reviewed. The mean age at the time of diagnosis was 4 years and 3 months, with 48% younger than six months of age. The average time for the follow-up period was 4 years and 2 months. There was not familiar occurrence. Six (16%) of the patients had associated heart disease. Seventeen (47%) had type A of WPW, 12 (33%) type B and 7 (20%) were not defined. An echocardiographic study was done in 20 patients (61%). Twenty-seven patients (75%) showed supraventricular tachycardia (SVT), which in 22 of these cases was the reason for seeking consultation. Children without SVT, 9 (25%), did not need any form of treatment. Twenty-four (889) of the patients with SVT required treatment to prevent recurrence. In the 27 studied episodes of SVT, Verapamil IV (55%) and vagal manoeuvres were the most efficient treatments. Seventeen (47%) of the patients presented a persistent WPW pattern and 11 (31%) experienced a normalization of their electrocardiogram with a mean time of 2 years-2 months. PMID- 1416553 TI - The influence of HLA-DRB1 genes on disease severity in rheumatoid arthritis. AB - OBJECTIVE: To explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis. DESIGN: Case series of patients with seropositive rheumatoid arthritis. SETTING: The outpatient clinic of the Division of Rheumatology, Mayo Clinic. PATIENTS: One hundred and two patients with seropositive, erosive rheumatoid arthritis and a minimum disease duration of 3 years. MEASUREMENTS: Patients were genotyped for both HLA-DRB1 alleles and were categorized according to the expression of one or two disease-linked HLA-DRB1 alleles. Identification of HLA-DRB1 alleles was done by the polymerase chain reaction and subsequent oligonucleotide hybridization. Homozygosity for allelic variants was confirmed by sequence analysis. Immunogenetically defined patient subgroups were retrospectively evaluated for joint destruction and patterns of disease manifestation, including rheumatoid organ disease. RESULTS: Of 102 patients, 98 (96%) expressed the disease-linked sequence polymorphism. Forty seven patients (46%) carried a double dose of the relevant sequence stretch: Twenty-eight patients expressed HLA-DRB1*04 variants on both alleles, and 19 combined an HLA-DRB*04 variant with HLA-DRB1*0101 or DRB1*1402. Nodular disease was present in 100% of patients typed as HLA-DRB1*04/04 and in 59% of patients typed as HLA-DRB1*04 and who had inherited only a single dose of the disease linked sequence polymorphism (P < 0.0001). Major organ systems were involved in 61% and 11% of these two patient groups, respectively (P < 0.0001); and joint surgery was required in 61% and 25% (P < 0.002), respectively. Patients typed as HLA-DR*04/01 had intermediate clinical courses. CONCLUSION: Genotyping patients with rheumatoid arthritis for both HLA-DRB1 alleles identifies clinical subsets with distinct profiles of disease manifestations. PMID- 1416554 TI - Lower endogenous androgen levels and dyslipidemia in men with non-insulin dependent diabetes mellitus. AB - OBJECTIVE: To compare plasma androgen levels in diabetic and nondiabetic men and to determine their relation to diabetic dyslipidemia. DESIGN: A population-based, case-control study. SETTING: Community. PARTICIPANTS: Men 53 to 88 years of age from the Rancho Bernardo, California, cohort who were screened for diabetes using an oral glucose tolerance test. MEASUREMENTS: Plasma androgen levels were compared in 44 men with untreated non-insulin-dependent diabetes mellitus and 88 age-matched men who had a normal glucose tolerance test. The relation of lipid and lipoprotein levels to androgen level and diabetic status was assessed before and after adjusting for covariates. RESULTS: Men with diabetes had significantly lower plasma levels of free (4.96 nmol/L compared with 5.58 nmol/L) and total testosterone (14.7 nmol/L compared with 17.4 nmol/L), dihydrotestosterone (428 pg/mL compared with 533 pg/mL), and dehydroepiandrosterone sulfate (DHEA-S) (1.92 mumol/L compared with 2.42 mumol/L) than nondiabetic men. They also had significantly lower high-density lipoprotein (HDL) cholesterol and significantly higher triglyceride levels. Differences were not explained by obesity, alcohol use, or cigarette habit. Overall, the total testosterone level, but not the free testosterone level, was positively correlated with the HDL cholesterol level (P = 0.009) and negatively correlated with the triglyceride level (P = 0.0001). Similar associations were seen in analyses restricted to the men without diabetes. CONCLUSIONS: Lower levels of endogenous androgens are seen in older diabetic men, and low androgen levels are associated with diabetic dyslipidemia. PMID- 1416555 TI - A waterborne outbreak in Missouri of Escherichia coli O157:H7 associated with bloody diarrhea and death. AB - OBJECTIVE: To describe and determine the source of a large outbreak of Escherichia coli O157:H7 (ECO157) infections in Missouri. DESIGN: A case-control study and a household survey. SETTING: A small city in a rural Missouri township that had an unchlorinated water supply. PATIENTS: Case patients were residents of or visitors to Burdine Township with bloody diarrhea or diarrhea and abdominal cramps occurring between 15 December 1989 and 20 January 1990. MEASUREMENTS: Escherichia coli O157 was isolated from 21 stool specimens. All isolates were resistant to sulfisoxazole, tetracycline, and streptomycin; produced Shiga-like toxins I and II; and had one 60-megadalton plasmid. RESULTS: Among the 243 case patients, 86 had bloody stools, 32 were hospitalized, 4 died, and 2 had the hemolytic uremic syndrome. In the case-control study, no food was associated with illness, but ill persons had drunk more municipal water than had controls (P = 0.04). The survey showed that, during the peak of the outbreak, bloody diarrhea was 18.2 times more likely to occur in persons living inside the city and using municipal water than in persons living outside the city and using private well water (P = 0.001). Shortly before the peak of the outbreak, 45 water meters were replaced, and two water mains ruptured. The number of new cases declined rapidly after residents were ordered to boil water and after chlorination of the water supply. CONCLUSIONS: This was the largest outbreak of ECO157 infections, the first due to a multiply resistant organism, and the first shown to be transmitted by water. System-wide chlorination as well as hyperchlorination during repairs might have prevented this outbreak. Both bloody and nonbloody diarrhea may be common manifestations of this infection, which is probably underdiagnosed because of the failure of routine stool cultures to identify the organism. Cities with deteriorating water systems using untreated water risk widespread illness from contaminated drinking water. PMID- 1416556 TI - Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study. AB - OBJECTIVE: To describe changes in negative emotions among participants of a cholesterol-lowering study. DESIGN: Cohort study. Quantitative evaluation of changes in negative emotions in relation to diet and plasma cholesterol levels before and after a 5-year dietary intervention program aimed at reducing plasma cholesterol levels. SETTING: Community-dwelling families of the Family Heart Study, Portland, Oregon. PARTICIPANTS: One hundred forty-nine men and 156 women from 233 families (mean age, 37.7 years). MEASUREMENTS: Changes in negative emotions including depression and aggressive hostility as measured by the Hopkins Symptom Checklist (SCL-90). RESULTS: Improvement in overall emotional state was noted for the entire sample. Those who consumed a low-fat, high complex carbohydrate diet at the end of the study showed significantly greater improvements in depression (P = 0.044; difference in improvement, 2.9 points) and aggressive hostility (P = 0.035; difference in improvement, 3.3 points) as well as a reduction in their plasma cholesterol levels (P = 0.024; difference in improvement, 2.7%) compared with those who ate a high-fat "American diet." CONCLUSIONS: Participation in a cholesterol-lowering program may not be associated with a worsening in emotional state. To the contrary, improvements in diet appear to be associated with reductions in depression and aggressive hostility as well as with lowered plasma cholesterol levels. PMID- 1416557 TI - The contribution of gastroesophageal reflux to chest pain in patients with coronary artery disease. AB - OBJECTIVE: To describe the effectiveness of investigating and treating the cause of refractory chest pain in patients with coronary artery disease who are receiving optimal antianginal therapy. DESIGN: Cohort study. SETTING: Tertiary referral center. PATIENTS: Between January 1988 and December 1989, 34 patients were identified as having angiographically proven coronary artery disease and atypical chest pain symptoms despite their having received aggressive medical or surgical antianginal therapy, or both. INTERVENTION: Patients with confirmed acid related symptoms were treated with high-dose histamine-2 (H2) blockers or omeprazole for 8 weeks in an open-label study. MEASUREMENTS: Esophageal manometry and simultaneous 24-hour pH and Holter studies; global improvement in or disappearance of chest pain. RESULTS: Of the 34 patients, 30 (88%) experienced their identical chest pain symptoms during the study. A total of 164 pain episodes was recorded: 38 (23.2%) correlated with acid reflux; 6 (3.7%) were related to cardiac ischemia; and the remaining 120 (73.2%) had no identifiable cause. Of these 30 patients, 20 (67%) had some of their episodes of chest pain (range, 14% to 100%) secondary to acid reflux. After 8 weeks of vigorous acid suppression, 13 of these 20 patients had marked improvement or resolution of chest pain. Four other patients had ischemia-related episodes of chest pain that responded to more aggressive antianginal therapy. No episodes of acid reflux were clearly followed by ischemic chest pain. One patient had both acid- and ischemic related episodes of chest pain that were indistinguishable. Overall, 24 of 34 (71%) patients had a definite cause of chest pain identified by combined pH and Holter monitoring. CONCLUSIONS: Gastroesophageal reflux disease is a common, treatable cause of chest pain in patients with coronary artery disease who have atypical symptoms and remain symptomatic despite aggressive antianginal therapy. Combined Holter and 24-hour esophageal pH studies are complementary investigations for elucidating the cause of chest pain in these patients. PMID- 1416558 TI - The prognostic role of left ventricular hypertrophy in patients with or without coronary artery disease. AB - OBJECTIVE: To examine the association between echocardiographically determined left ventricular hypertrophy and mortality in patients with and without coronary artery disease. DESIGN: Cohort study with a mean follow-up period of 4 years. SETTING: An inner-city public hospital in Chicago. PATIENTS: A cohort of 785 patients, most of whom were black and had hypertension. INTERVENTIONS: Coronary arteriography for presumed coronary artery disease and echocardiography. MAIN OUTCOME MEASURE: All-cause and cardiac mortality. RESULTS: Left ventricular hypertrophy, based on left ventricular mass corrected for body surface area, was present in 194 of 381 patients (51%) with coronary artery disease and in 162 of 404 patients (40%) without coronary artery disease. Patients with left ventricular hypertrophy had worse survival than those without hypertrophy in both the group with coronary artery disease and the group without coronary artery disease. After adjustment was made for age at baseline, sex, and hypertension, the relative risk for death from any cause in patients with hypertrophy compared with patients without hypertrophy was 2.14 (95% CI, 1.24 to 3.68) among those with coronary artery disease and 4.14 (CI, 1.77 to 9.71) among those without coronary artery disease. CONCLUSIONS: Echocardiographically determined left ventricular hypertrophy is an important prognostic marker in patients with or without coronary artery disease. The effect of reversing ventricular hypertrophy in patients with and without coronary disease deserves further study. PMID- 1416559 TI - Hepatitis B in patients with HIV infection: relationship to AIDS and patient survival. PMID- 1416560 TI - The downsizing of internal medicine residency programs. AB - A variety of forces are converging to reduce the number of internal medicine residency positions offered in this country. This reduction, referred to as downsizing, has been proposed as the solution to several of the problems facing internal medicine. We examine the forces that underlie the current enthusiasm for downsizing; we consider the alternative strategies by which downsizing might be implemented; and we consider the implications of these alternatives on different groups of stakeholders. Although downsizing may represent a legitimate approach to real problems, any mechanism to reduce the number of training positions in internal medicine will have broad implications for medical education and patient care well into the next century. Special efforts must be taken to ensure that downsizing will not exacerbate the existing problem of overspecialization and limited access to care. PMID- 1416561 TI - Detection of renovascular hypertension. State of the art: 1992. AB - PURPOSE: To review recent advances in detecting renovascular hypertension. DATA SOURCES: Original English-language reports obtained through a MEDLINE search for the years 1987 to 1991. Also, a manual search through Index Medicus as well as bibliographies of original reports and selected review articles. STUDY SELECTION AND DATA EXTRACTION: Cited studies were critically reviewed with emphasis on study size, patient sample, methods, diagnostic criteria, and reproducibility of results. Where applicable, reviews that combined the results of smaller studies are cited. RESULTS: A sensitivity of 74% and a specificity of 89% have been reported for the captopril test and of 93% and 95%, respectively, for captopril scintigraphy with diethylenetriaminepentaacetic acid (DTPA). The sensitivity and specificity of renal vein renin determination are 80% and 62%, respectively and may increase with the use of stricter technical criteria and maneuvers to stimulate renin secretion. These tests differentiate renovascular hypertension from essential hypertension more reliably than from asymmetric renal parenchymal disease; however, they do not reliably distinguish unilateral from bilateral stenosis. Other tests are less widely used. Intravenous pyelography (sensitivity, 74.5%; specificity, 86.2%) has the disadvantages of radiation and dye load exposure. Intravenous angiography is expensive and invasive and does not always enable visualization of the origin of the renal artery. The roles of duplex ultrasound and magnetic resonance angiography remain to be clarified. CONCLUSIONS: Noninvasive tests are cost effective and have a high predictive value in patients with clinical clues suggestive of renovascular hypertension. These tests are not recommended for use in patients with a low likelihood of disease. PMID- 1416562 TI - The stress response and the regulation of inflammatory disease. AB - The molecular and biochemical bases for interactions between the immune and central nervous systems are described. Immune cytokines not only activate immune function but also recruit central stress-responsive neurotransmitter systems in the modulation of the immune response and in the activation of behaviors that may be adaptive during injury or inflammation. Peripherally generated cytokines, such as interleukin-1, signal hypothalamic corticotropin-releasing hormone (CRH) neurons to activate pituitary-adrenal counter-regulation of inflammation through the potent antiinflammatory effects of glucocorticoids. Corticotropin-releasing hormone not only activates the pituitary-adrenal axis but also sets in motion a coordinated series of behavioral and physiologic responses, suggesting that the central nervous system may coordinate both behavioral and immunologic adaptation during stressful situations. The pathophysiologic perturbation of this feedback loop, through various mechanisms, results in the development of inflammatory syndromes, such as rheumatoid arthritis, and behavioral syndromes, such as depression. Thus, diseases characterized by both inflammatory and emotional disturbances may derive from common alterations in specific central nervous system pathways (for example, the CRH system). In addition, disruptions of this communication by genetic, infectious, toxic, or pharmacologic means can influence the susceptibility to disorders associated with both behavioral and inflammatory components and potentially alter their natural history. These concepts suggest that neuropharmacologic agents that stimulate hypothalamic CRH might potentially be adjunctive therapy for illnesses traditionally viewed as inflammatory or autoimmune. PMID- 1416563 TI - Life care at Golden Acres. PMID- 1416564 TI - Genetic determination of susceptibility and severity in rheumatoid arthritis. PMID- 1416565 TI - Androgens, lipids, and cardiovascular risk. PMID- 1416566 TI - MRFIT, "MS FIT," and alcohol use. PMID- 1416568 TI - SI units and the Friedewald formula. PMID- 1416567 TI - Thrombosis in antithrombin-III deficiency. PMID- 1416569 TI - Watchful waiting and craniopharyngioma. PMID- 1416570 TI - Pancytopenia from using trimethoprim and methotrexate. PMID- 1416571 TI - Clinical evaluation for sinusitis. Making the diagnosis by history and physical examination. AB - OBJECTIVE: To identify the most useful clinical examination findings for the diagnosis of acute and subacute sinusitis. DESIGN: Prospective comparison of clinical findings with radiographs. SETTING: General medicine clinics at a university-affiliated Veterans Affairs Medical Center. PATIENTS: Two hundred forty-seven consecutive adult men with rhinorrhea (51%), facial pain (22%) , or self-suspected sinusitis (27%) (median age, 50 years; median duration of symptoms, 11.5 days). MEASUREMENTS: Patients were examined by a principal investigator (86%) or by a staff general internist, internal medicine resident (postgraduate year 2 or 3), or physician assistant, all blinded to radiographic results. All examiners recorded the presence or absence of 16 historical items, 5 physical examination items, and the clinical impression for sinusitis (high, intermediate, or low probability). The criterion standard was paranasal sinus radiographs (4 views), which were interpreted by radiologists blinded to clinical findings. RESULTS: Thirty-eight percent of patients meeting entrance criteria had sinusitis. Sensitivity, specificity, and likelihood ratios were measured for clinical items. Logistic regression analysis showed five independent predictors of sinusitis: maxillary toothache (odds ratio, 2.9), transillumination (odds ratio, 2.7), poor response to nasal decongestants or antihistamines (odds ratio, 2.4), colored nasal discharge reported by the patient (odds ratio, 2.2), or mucopurulence seen during examination (odds ratio, 2.9). THe overall clinical impression was more accurate than any single finding: high probability (likelihood ratio, 4.7, intermediate (likelihood ratio, 1.4), low probability (likelihood ratio, 0.4). CONCLUSIONS: General internists, focusing on five clinical findings and their overall clinical impression, can effectively stratify male patients with sinus symptoms as having a high, intermediate, or low probability of sinusitis. PMID- 1416572 TI - Octreotide treatment of acromegaly. A randomized, multicenter study. AB - OBJECTIVE: To determine the effects of the somatostatin analog, octreotide acetate, in patients with acromegaly. DESIGN: Double-blind, randomized trial. SETTING: Fourteen university-affiliated medical centers. PATIENTS: One hundred fifteen acromegalic patients, 70% of whom had persistent disease after pituitary surgery or radiotherapy. INTERVENTION: Subcutaneous octreotide, 100 micrograms, or placebo every 8 hours for 4 weeks. Four weeks after the end of treatment, patients were randomized to receive 100 or 250 micrograms octreotide subcutaneously every 8 hours for 6 months. RESULTS: After 2 weeks of treatment, a single 100-micrograms injection reduced mean serum growth hormone (GH) to 30% of the pretreatment concentration within 2 hours. The integrated mean GH level was reduced over 8 hours from 39 +/- 11 micrograms/L to 9 +/- 2 micrograms/L (P less than 0.001). Mean plasma insulin-like growth factor-1 (IGF-1) was reduced from 5100 +/- 400 U/L to 2400 +/- 400 U/L (P less than 0.001). After 6 months, the mean GH was reduced from 39 +/- 13 to 15 +/- 4 micrograms/L by 300 micrograms of octreotide and from 29 +/- 5 micrograms/L to 9 +/- 2 micrograms/L by 750 micrograms of octreotide daily. The mean IGF-1 concentration was suppressed to 2100 +/- 300 and 2500 +/- 400 U/L after 300 and 750 micrograms octreotide, respectively. Integrated mean GH levels were reduced to < 5 micrograms/L in 53% (95% CI, 39% to 67%) and 49% (CI, 35% to 63%), and IGF-1 levels were normal in 68% (CI, 54% to 82%) and 55% (CI, 40% to 70%) of patients receiving low- and high dose octreotide, respectively. A substantial decrease in headache, amount of perspiration, joint pain, and finger circumference occurred in two thirds of the patients. The pituitary size was reduced in 19% (CI, 5% to 33%) and 37% (CI, 22% to 52%) of patients receiving 6 months of low- and high-dose octreotide, respectively. Ten percent and 13% of patients in each treatment group developed transient diarrhea; 10% and 14%, biliary sludge; and 6% and 18%, cholelithiasis, respectively. CONCLUSION: Octreotide effectively decreased GH and IGF-1 concentrations in 53% and 68% of patients, respectively. The higher dose resulted in increased frequency of tumor shrinkage but added no biochemical or clinical benefit. PMID- 1416573 TI - Rapid reduction of left ventricular hypertrophy in acromegaly after suppression of growth hormone hypersecretion. AB - OBJECTIVE: To examine the possible role of growth hormone as a pathogenetic factor in the development of myocardial hypertrophy in acromegaly. DESIGN: An uncontrolled clinical trial. SETTING: Tertiary-care medical center. PATIENTS: Sixteen patients with acromegaly were stratified into two groups: Group I (n = 10) had left ventricular hypertrophy (LVH), and group II (n = 6) did not have LVH. INTERVENTION: Therapy with octreotide acetate (SMS 201-995), a long-acting somatostatin analog (mean dose, 538 micrograms/d), was administered for 2 months. MEASUREMENTS: Plasma growth hormone and insulin-like growth factor I (IGF-I) concentrations, hand volume, and echocardiographic left ventricular dimensions and mass were measured at baseline and at 1 week and 2 months after the start of therapy. RESULTS: Before octreotide therapy, both groups had similar hand volumes and similar growth hormone and IGF-I hypersecretion. Both groups showed a reduction in growth hormone at 2 months (mean reduction, 13.7 micrograms/L in patients with LVH [P < 0.01] and 14.1 micrograms/L in patients without LVH [P < 0.05]). Plasma IGF-I was also decreased (mean reduction, 305 micrograms/L in patients with LVH [P < 0.01] and 304 micrograms/L in patients without LVH [P < 0.05]). Reduction of growth hormone and IGF-I hypersecretion in patients with LVH was associated with a rapid decrease in left ventricular mass (339 g to 299 g, P < 0.01) within 1 week, which was sustained at 2 months (274 g, P < 0.04). Patients without LVH showed no statistical change in left ventricular mass. In patients with LVH, the decrease in left ventricular mass correlated with the octreotide-induced decrease in growth hormone (r = 0.79, P less than 0.05) but not with blood pressure. Blood pressure, left ventricular dimensions, and percent of fractional shortening were not altered by therapy in either group. Hand volume decreased in both groups. CONCLUSIONS: Normalization of growth hormone secretion is associated with reduction of left ventricular mass in acromegalic patients with LVH within 1 week of initiating therapy with octreotide. PMID- 1416574 TI - Treatment of shigellosis: III. Comparison of one- or two-dose ciprofloxacin with standard 5-day therapy. A randomized, blinded trial. AB - OBJECTIVE: To determine whether a single dose, or 2 doses, of ciprofloxacin are as effective as 5-day, 10-dose therapy for the treatment of shigellosis in adult men who are moderately to severely ill. DESIGN: Randomized, double-blind clinical trial. SETTING: A diarrhea treatment center in the capital city of a developing country, Bangladesh. PATIENTS: A total of 128 adult men with dysentery of less than 96 hours duration. All had Shigella organisms isolated from a culture of stool. INTERVENTIONS: Patients were randomly assigned to receive either a single 1-gram dose of ciprofloxacin at admission to the study (single-dose group; n = 40), a 1-gram dose of ciprofloxacin at admission and 24 hours later (2-dose group; n = 43), or 500 mg of ciprofloxacin every 12 hours for 5 days (10 dose group; n = 35). All patients were hospitalized for 6 days. MEASUREMENTS: Stools were collected individually; their character and consistency were recorded and cultured daily. A physical examination and recording of symptoms were done daily, and the temperature was measured every 4 hours. Therapy was considered to have failed in patients who did not have improvement in the signs and symptoms of dysentery after 72 hours of therapy or in patients who on study day 5 had more than nine stools, or more than two watery stools, or were febrile. RESULTS: There were no treatment failures in the 78 patients infected with species of Shigella other than Shigella dysenteriae type 1. Among the 40 patients infected with S. dysenteriae type 1, treatment failed in 4 of the 10 patients who received single dose therapy, 2 of the 15 patients who received 2-dose therapy, and none of the 15 patients who received 10-dose therapy (P = 0.017, single-dose therapy group compared with 10-dose group; P = 0.15 for the single-dose group compared with the 2-dose group; P > 0.2 for the 2-dose group compared with the 10-dose group). CONCLUSIONS: A single 1-gram dose of ciprofloxacin is effective therapy for patients infected with species of Shigella other than S. dysenteriae type 1. Single-dose therapy is inferior to 10-dose therapy for treating patients infected with S. dysenteriae type 1. PMID- 1416575 TI - Low accuracy of color Doppler ultrasound in the detection of proximal leg vein thrombosis in asymptomatic high-risk patients. The RD Heparin Arthroplasty Group. AB - OBJECTIVE: To evaluate the ability of color Doppler ultrasound to detect proximal deep venous thrombosis (DVT) in asymptomatic high-risk patients who subsequently underwent contrast venography. DESIGN: Prospective cohort study using blinded observers, with contrast venography as the comparison standard. SETTING: Seven medical centers (university and community hospitals) participating in a clinical trial of low-molecular-weight heparin for prevention of DVT. PATIENTS: A total of 385 consecutive patients undergoing elective unilateral hip or knee replacement. MEASUREMENTS: Ten days after surgery or before hospital discharge (whichever occurred first), patients had bilateral color Doppler ultrasound examinations of the proximal veins of the lower extremities. Subsequently, a contrast venogram of the operated leg was obtained. RESULTS: Color Doppler ultrasound studies and venograms were both evaluable in 319 of the 385 patients. Deep venous thrombosis was identified by contrast venography in 80 patients (prevalence, 25%; 95% CI, 20% to 30%) and involved the proximal veins in 21 patients (prevalence, 7%; CI, 4% to 10%). For proximal DVT, color Doppler ultrasound showed poor sensitivity (38%; CI, 18% to 62%), moderately good specificity (92%; CI, 89% to 95%), and a poor positive predictive value for this population (26%). CONCLUSION: Color Doppler ultrasound examinations are insensitive to proximal DVT in asymptomatic high-risk patients and should not be substituted for venography for identifying proximal DVT in such patients. PMID- 1416576 TI - Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials. AB - OBJECTIVE: To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy. DESIGN: Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials. SETTING: Multiple centers in the United States. PATIENTS: Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety. INTERVENTION: Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks. MEASUREMENTS: Changes in mean hematocrit, transfusion requirement, and quality of life. RESULTS: Sixty nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections. CONCLUSION: Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L. PMID- 1416577 TI - Shoulder girdle lipomatosis. PMID- 1416578 TI - Assessing housestaff diagnostic skills using a cardiology patient simulator. AB - OBJECTIVE: To assess the cardiovascular physical examination skills of internal medicine housestaff. DESIGN: Cross-sectional assessment of housestaff performance on three valvular abnormality simulations conducted on the cardiology patient simulator, "Harvey." Evaluations were done at the beginning (session I) and end (session II) of the academic year. SETTING: Duke University Medical Center internal medicine training program. SUBJECTS: Sixty-three (59%) of 107 eligible internal medicine housestaff (postgraduate years 1 through 3) agreed to participate and completed session I; 60 (95%) completed session II. MEASUREMENTS: All volunteers were tested on three preprogrammed simulations (mitral regurgitation, mitral stenosis, and aortic regurgitation). RESULTS: The overall correct response rates for all housestaff were 52% for mitral regurgitation, 37% for mitral stenosis, and 54% for aortic regurgitation. No difference was noted in correct response rates between sessions I and II. For mitral regurgitation, correct assessment of the contour of the holosystolic murmur predicted a correct diagnosis (P = 0.002). For mitral stenosis, identification of an opening snap and proper characterization of the mitral area diastolic murmur predicted a correct diagnosis (P < 0.0001). No individual observations were noted for the aortic regurgitation simulation, whose identification by the housestaff was associated with a correct diagnosis. CONCLUSIONS: Housestaff had difficulty establishing a correct diagnosis for simulations of three common valvular heart diseases. Accurate recognition of a few "key" observations was associated with a correct diagnosis in two of the three diseases. Teaching housestaff to elicit and interpret a few critical signs accurately may improve their physical diagnosis abilities. PMID- 1416579 TI - Carcinoma of the male breast. AB - The natural history and current management of carcinoma of the breast in men is reviewed. Articles published from 1942 to 1992 on the natural history, clinical manifestations, diagnosis, and treatment of carcinoma of the breast in men were identified using CANCERLINE and MEDLINE. Carcinoma of the breast affects approximately 1000 men per year in the United States; 300 men per year will die of metastatic disease. The mean age at diagnosis is 59 years. The causes of breast cancer in men are unknown. The most common clinical manifestation of breast cancer in men is a painless, firm subareolar mass or a mass in the upper outer quadrant of the breast. Diagnosis can be confirmed by fine-needle aspiration or surgical biopsy. Infiltrating ductal carcinoma is the predominant histologic type. Treatment is similar to that of women with breast cancer. Men with axillary nodal metastasis should receive adjuvant systemic combination chemotherapy or tamoxifen, or both, after primary surgical treatment. Because most men with carcinoma of the breast have estrogen- and progesterone-receptor positive tumors, distant metastatic disease should be treated initially with hormonal therapies. The epidemiology, prognostic factors, survival by stage, pattern of metastasis, and response to treatment in men are similar to those in women with breast carcinoma. The data suggest, however, that breast cancers in men are more likely to respond to hormonal manipulation. PMID- 1416580 TI - General internal medicine and general internists: recognizing a national need. Federated Council for Internal Medicine. AB - The Federated Council for Internal Medicine (FCIM) comprises the American Board of Internal Medicine, American College of Physicians, American Society of Internal Medicine, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, and the Society of General Internal Medicine. The Council was established in 1975 to speak with a collective voice for the specialty of internal medicine. In 1992, the Council developed the following statement in conjunction with its endorsement of a target of 50% of internal medicine residency graduates entering the practice of general internal medicine. PMID- 1416581 TI - Intuition of a clinical sort. PMID- 1416582 TI - Has medicine outgrown physical diagnosis? PMID- 1416583 TI - Medical malpractice: folklore, facts, and the future. PMID- 1416584 TI - HIV transmission in a dental practice. PMID- 1416585 TI - HIV transmission in a dental practice. PMID- 1416586 TI - HIV transmission in a dental practice. PMID- 1416587 TI - HIV transmission in a dental practice. PMID- 1416588 TI - Intracerebral bacillary angiomatosis in HIV. PMID- 1416589 TI - Posey palsy. PMID- 1416590 TI - Colchicine and secondary amyloidosis. PMID- 1416591 TI - Genetics and tuberculosis resistance. PMID- 1416592 TI - Genetics and tuberculosis resistance. PMID- 1416593 TI - Coping with HIV infection: why people delay care. PMID- 1416594 TI - The hassle factor. PMID- 1416595 TI - Comportment and health care reform. PMID- 1416596 TI - Beneficial effects of reduced oxygen tension and perfusion in long-term hematopoietic cultures. AB - Growth of hematopoietic stem and progenitor cells found in the MNC fraction of human cord blood was evaluated under atmospheres containing reduced (5%) and normal (20%) oxygen tension. Reduced oxygen tension increased total cell numbers by as much as 5-fold in cord blood suspension cultures, but this effect was less pronounced in cultures containing an irradiated bone marrow stromal cell layer. However, reduced oxygen tension resulted in a substantial increase in both the number and frequency of colony-forming cells observed in both types of LTHC studied. Under low oxygen, CFU-C progenitor cell numbers were as much as 10-fold higher. Finally, reduced oxygen tension slowed the rate of irradiated stromal layer degeneration, as judged by cell counts and microscopic examination. These results indicate that low oxygen, which better approximates the in vivo environment, enhances the growth and maintenance of human stromal and progenitor cells in vitro. These low oxygen findings were then applied to a murine model LTHC perfusion system. In this system, irradiated 3T3 stromal layer integrity was improved under low oxygen and was substantially further improved with continuous medium perfusion. Cell counts and flow cytometry analysis indicated that the total cell production and the production of immature cells from murine bone marrow MNC on irradiated 3T3 cells were significantly enhanced under low oxygen with perfusion. After three weeks of culture, a 24-fold higher number of Thy1.2lo F4/80- MAC1- cells (indicative of murine stem and progenitor cells) was observed in the perfusion system as compared with static culture under ambient oxygen. PMID- 1416597 TI - Modulation of glutathione level in CHO cells. Effects of oxygen concentration and prior exposure to hypoxia. AB - A microtiter-plate assay has been developed for total intracellular glutathione that facilitates multiple-sample analysis and reduces the amount of time and chemicals required. Sonication time, pH, and storage conditions were identified as key parameters that affect the accuracy of the assay. Using this assay, it was found that CHO cells increase their glutathione level under higher oxygen tension. This adaptive response suggests that a rise in glutathione may be used as an indicator of oxidative stress. Based on this criterion, it was found that hypoxic and anoxic cells are sensitized to reoxygenation. This sensitization could not be attributed to a drop in glutathione during low oxygen exposure because the glutathione content reached a basal level at a PO2 of about 40 torr. PMID- 1416598 TI - Optimization of a roller bottle process for the production of recombinant erythropoietin. PMID- 1416599 TI - Polystyrene macroporous bead support for mammalian cell culture. PMID- 1416600 TI - Monoclonal antibody production using the porous glass bead immobilization technique. Serum-free perfusion. PMID- 1416601 TI - A single-cell model for CHO cells. PMID- 1416602 TI - Analysis of rate-limiting reactions in cephalosporin biosynthesis. PMID- 1416603 TI - Approaches to understanding and manipulating the biosynthetic potential of plant roots. PMID- 1416604 TI - Cell-bubble interactions. Mechanisms of suspended cell damage. PMID- 1416605 TI - Carbohydrate metabolism in insect cell cultures during cell growth and recombinant protein production. PMID- 1416606 TI - Hepatic tissue engineering. Development of critical technologies. PMID- 1416607 TI - Surface-grafted cell-binding peptides in tissue engineering of the vascular graft. PMID- 1416608 TI - Three-dimensional cell cultures mimic tissues. AB - Three-dimensional cell culture using gels of type I collagen is a flexible method for studying cell behavior in a tissuelike environment. With only small changes in the basic protocol, we were able to encapsulate neutrophils, hepatocytes, and PC12 cells. As demonstrated by cell-specific assays for migration, protein secretion, and growth factor induction, the encapsulated cells were viable and functional. In future studies, we will focus on using these cell cultures to study cell movement, cell growth, and cell function in carefully controlled tissuelike environments. PMID- 1416609 TI - Dynamic metabolic control theory. A methodology for investigating metabolic regulation using transient metabolic data. AB - The purposes of the dynamic metabolic control theory are to provide a theoretical basis for estimating the control coefficients using the transient metabolic responses and to gain insights into the metabolic regulation in the transient states. The numerical application of this theory is relatively straightforward: it involves a standard linear regression and a matrix multiplication. Although the equations are exact only for linear kinetics, they yield relatively good estimates of the control coefficients for nonlinear systems. PMID- 1416610 TI - A continuous perfusion bioreactor for long-term bone marrow culture. PMID- 1416611 TI - Use of magnetic resonance imaging to analyze the performance of hollow-fiber bioreactors. AB - Preliminary experiments were described that demonstrate that MRI is an effective tool for the noninvasive study of hollow-fiber bioreactors. Flow-compensated velocity-encoding pulse sequences were successively applied to analyze the velocity patterns in a module operated without cells, with an artificially induced flow field perturbation. Diffusion damping pulse sequences were also used to spatially resolve regions of cell growth in a bioreactor. These experiments provide the necessary basis from which future flow and spectroscopic studies can be conducted. PMID- 1416612 TI - Degradation of secreted proteins in Escherichia coli. PMID- 1416613 TI - Adaptive control strategy for maintaining dissolved oxygen concentration in high density growth of recombinant E. coli. PMID- 1416614 TI - An FDA perspective of manufacturing changes for products in human use. PMID- 1416615 TI - Alternative strategies to the scaleup of animal cells. AB - The use of porous microcarriers has given manufacturers the option of having a high cell density/medium volume (10-100 L)/high specific productivity/long-term process. The advantages of the system are listed in Table 7 and many of the criteria listed in Table 1 are met. The question of being able to license products from continuous processes has been addressed and guidelines are being prepared. Methods are available to compare the master and end-of-process (extended) cell banks to ensure that no change has occurred to the cell or product. Rigid attention to process definition and validation, as well as to the definition of production lots, overcomes many of the other reservations. In conclusion, the method has been demonstrated as technically feasible, economically advantageous, and licensable and the many advantages of a high density perfusion process (listed in Table 8) make porous microcarrier technology an ideal scaleup process because it is a simple, reliable, and scalable system. PMID- 1416616 TI - The importance of cell physiology to the performance of animal cell bioreactors. AB - This report has pointed out the following: (1) the new animal cell products that will be produced commercially will have large dollar markets and will, together with cost containment and competitive pressures, place a greater emphasis on the reduction of the cost of production through the selection of appropriate culture technology; (2) the benefits to be gained by working with basic biological processes in animal cell culture that will increase cell density, cell productivity, and product quality; (3) the need to work with reactor technologies that can affect the basic biology of the cell in these positive ways; (4) it appears worthwhile to explore immobilized, high cell density culture technologies as a possible means to achieve the objectives by affecting the basic regulation of the cell through fundamental cell/cell environment biological processes. PMID- 1416617 TI - Vector construction, transformation, and gene amplification in Clostridium acetobutylicum ATCC 824. AB - In order to alter the primary metabolism of C. acetobutylicum, we have constructed E. coli- or B. subtilis-C. acetobutylicum shuttle vectors that could be used to deliver homologous fermentative genes into C. acetobutylicum ATCC 824. The plasmid copy number and plasmid stability in C. acetobutylicum for several of these plasmids were determined. We have also developed a protocol for the electrotransformation of C. acetobutylicum ATCC 824. Difficulty in the transformation of C. acetobutylicum ATCC 824 with vectors containing DNA from E. coli plasmids was found to be due to the existence of a restriction system in this strain. This type II restriction endonuclease, named Cac824I, recognizes the sequence 5'-GCNGC-3' and cuts ColE1 plasmids frequently. One of the vectors, pFNK1, possessing a variety of unique cloning sites was used in the amplification of one acid (PTB) and one solvent (AADC) formation gene. The corresponding enzyme activities were amplified in C. acetobutylicum as shown by enzyme assays and SDS PAGE gels of cell extracts. PMID- 1416618 TI - Production of biologically active human protein C in the milk of transgenic mice. PMID- 1416619 TI - Bioremediation. A challenging application of biochemical engineering principles. PMID- 1416620 TI - Kinetics of the cell cycle of Saccharomyces cerevisiae. PMID- 1416621 TI - Perfusion cultures of hybridoma cells for monoclonal antibody production. PMID- 1416622 TI - Development and scaleup of controlled secretion processes for improved product recovery in animal cell culture. PMID- 1416623 TI - Regulation of genetic expression in shear stress-stimulated endothelial cells. AB - There is increasing evidence that endothelial cells respond to the initiation of mechanical stress by the generation of certain second messengers and the activation of specific metabolic pathways. These rapid alterations in cellular function are accompanied by alterations in protein synthesis that are detectable several hours after initiation of the mechanical stress. The molecular mechanisms by which changes in the cytosol are converted to altered genetic expression in the nucleus are not known. Because agonist-induced modulations in the rate of synthesis of tPA and ET have been associated with the Fos and Jun protein families, it seems reasonable to propose that genetic expression in shear stress- or mechanical strain-stimulated endothelial cells is also regulated by selective induction of fos and jun gene products. Testing of this hypothesis is actively under way in our laboratory. PMID- 1416624 TI - Complete but transient visual loss after yttrium aluminum garnet laser transscleral cyclocoagulation. AB - We report the case of a patient who had no light perception after neodymium:yttrium aluminum garnet (Nd:YAG) laser transscleral cyclocoagulation. To the best of our knowledge, no similar cases have been reported previously. A 56-year-old man with intractable open-angle glaucoma had intraocular pressures of 42 mmHg OD and 35mmHg OS. The patient rejected a recommended filtering operation, although argon laser trabeculoplasty and maximal medication had been ineffective OU. We used the free-running mode of an Nd:YAG laser to treat this patient. After the tenth application, the patient suddenly noticed acute visual loss OD. He was admitted to the hospital immediately. His retinal vessels and papilla OD could not be seen during fluorescein angiography. We administered pulsed corticosteroids and a stellate ganglion block. Gradually, his symptoms improved. The indications for using Nd:YAG laser cyclocoagulation have been expanded. However, as a result of our experience in this patient, we concluded that such therapy should be limited to cases not amenable to other forms of medical and surgical treatment. PMID- 1416625 TI - Silicone oil-induced corneal hydrops? AB - A 27-year-old man with a personality disorder, who did not have keratoconus previously, recently presented with a clinical picture resembling acute corneal hydrops OS three years after silicone oil injection for a complicated retinal detachment. Although self-induced trauma could not be excluded completely, this case might represent a newly described late corneal complication of intracameral silicone oil. PMID- 1416626 TI - Retinoblastoma, microphthalmia, coloboma, and neuroepithelioma of the pineal body. AB - A one-month-old infant boy was examined early in life because his mother had bilateral retinoblastoma and his father had bilateral microphthalmia. The ophthalmologist found his right eye was normal size with a coloboma of the iris, choroid, and retina. The left eye was microphthalmic with a coloboma of the uveal tract and retina. A vascularized fluffy white mass in the posterior pole was diagnosed clinically as a retinoblastoma. The tumor regressed with radiation. When the patient was four years of age, a large tumor was found in the region of the pineal recess, causing hydrocephalus and seizures. A biopsy showed an undifferentiated malignant neuroepithelial neoplasm. The patient died within three months of diffuse central nervous system tumor. The unusual findings of a retinoblastoma in a microphthalmic eye with bilateral colobomas and a neuroepithelial neoplasm of the pineal gland are discussed. PMID- 1416627 TI - Leukemic infiltrate versus anterior uveitis. AB - Anterior segment leukemic infiltrate (ASLI) is rare; it is found in 0.5% to 2.5% of all leukemic relapses. Its clinical manifestations, at times, are similar to those of anterior uveitis (AU). We report the cases of three patients, all of whom had ASLI as their primary manifestation of relapse. We observed some major clinical differences between ASLI and AU that may help differentiate these two conditions without using anterior chamber paracentesis and/or iris biopsy. The development of resistance to leukemic therapy is the major factor in treatment failure. PMID- 1416628 TI - Radial keratotomy: improved predictability. PMID- 1416629 TI - New high-index visolett magnifier. AB - The high-index Visolett magnifier (index, 1.806) is an optically designed glass paperweight magnifier. It magnifies 2.49x, is 32mm in diameter, nonfocusable, and rests on paper. All Visoletts commercially available are made of crown glass (index, 1.523). The 32mm high-index Visolett has become commercially available recently. The use of high-index material increases the image size by 39%. PMID- 1416630 TI - Toxicity of methyl methacrylate monomer in orbital and cranial surgery. AB - Methyl methacrylate (plastic bone cement) can be prepared by mixing a vial of liquid monomer with a powder. The monomer can release a toxic vapor. We measured the exposure of operating room personnel to this toxic substance. We believe that an awareness of the potential toxicity of the monomer is important and that devices to limit its exposure to personnel should be used in operating rooms. PMID- 1416631 TI - X-linked pathologic myopia. AB - We examined a patient with decreased visual acuity and macular changes attributable to pathologic myopia. Thirteen additional family members were examined, and historic information was obtained on their relatives. A pedigree spanning six generations was constructed that demonstrated an X-linked mode of inheritance. This finding has important genetic and therapeutic implications for similarly affected patients. PMID- 1416632 TI - Orbital cellulitis and cavernous sinus thrombosis after cataract extraction and lens implantation. AB - Orbital cellulitis as a complication of ophthalmic surgery is uncommon. We treated a patient who had orbital cellulitis and cavernous sinus thrombosis three weeks after uncomplicated cataract extraction and lens implantation. Sinus x-rays showed sphenoid sinus opacification. Computed tomographic scan confirmed the sphenoid sinus disease, and no abscess was found. The patient recovered completely after treatment with intravenous antibiotics. Most orbital cellulitis is secondary to sinus disease. The trauma of surgery and the retrobulbar block must be considered possible causative factors in this patient, but sinus disease is still the most likely cause. Intraocular inflammation did not increase during the illness although the intraocular pressure rose from 14 to 23mmHg. PMID- 1416633 TI - Intraoperative laryngeal electromyographic assessment of patients with immobile vocal fold. AB - The differential diagnosis of laryngeal ankylosis versus paralysis is occasionally difficult in patients with immobile vocal folds. Eight patients with acute and chronic evidence of vocal fold immobility were investigated by intraoperative electromyography (IEMG) during planned microlaryngoscopy. Bipolar hook wire electrodes were inserted into the thyroarytenoid muscle, of which the electrical activity was monitored during neuromotor blockade and emergence from anesthesia. The normal side and the side with ankylosis or stenosis showed normal IEMG activity. There was progressive recruitment of larger motor units during recovery from muscle relaxation. Patients with laryngeal paralysis failed to show such recruitment patterns. Thus, IEMG can be used as a diagnostic tool during operative laryngoscopy to differentiate neuromotor injury from anatomic causes of vocal fold immobility. The advantages of IEMG are its ease of application and certainty of electrode position. It can also be used to monitor recurrent nerve integrity and detect early laryngospasm. Further IEMG clinical study is warranted. PMID- 1416634 TI - Experimental tracheal replacement using a revascularized jejunal autograft with an implantable Dacron mesh tube. AB - Defects comprising more than 50% of the trachea cannot be reliably reconstructed by any current technique or prosthesis. A composite tracheal replacement implant consisting of a Dacron-urethane mesh tube and revascularized jejunal autograft was applied to this problem. This composite implant was used to replace 7 to 10 cm of trachea in eight dogs. The implant was sewn to the outside (serosal surface) of the jejunum to provide permanent structural support to the autograft, and an intraluminal silicone tube was placed inside the jejunal segment and left for 4 weeks following reconstruction. Six of eight animals survived the predetermined time periods and were killed painlessly in groups of two animals at 1, 2, and 6 months after removal of the intraluminal silicone tube. Postoperative intubation, ventilation, or tracheostomy was not necessary. Excessive secretions were not seen in any of the animals, and a fair to good performance status was maintained until death in all but one animal. Histologic examination revealed slight thinning of the jejunal mucosa, with no change in the jejunal muscularis. These data suggest that with further refinement this composite implant may be a viable reconstructive option in humans. PMID- 1416635 TI - Subglottic ulceration and healing following endotracheal intubation in the neonate: a morphometric study. AB - In neonates, acquired subglottic stenosis is the most serious long-term complication of endotracheal intubation and is due primarily to posttraumatic fibrosis of the infant larynx. We have examined 78 larynges, 75 of which were intubated, from infants ranging in gestation from 22 to 40 weeks, and who survived from a few hours to up to 300 days. Each larynx was morphometrically assessed for the extent of acute injury, indicated by the percentage of epithelial loss, and healing, indicated by the percentage of a subglottic ulcer covered by metaplastic squamous epithelium. Results show that acute injury is almost invariable, and up to 100% of the subglottic epithelium may be lost within a few hours of intubation, but that progression of injury is relatively short lived. Ulcer healing starts after a few days, rapidly progresses from day 10, and in the majority of cases is complete after 30 days. This study suggests that long standing acute injury in the subglottis is the exception rather than the rule, even with the endotracheal tube remaining in place. PMID- 1416636 TI - Causes of facial nerve paresis after translabyrinthine surgery for acoustic neuroma. AB - Forty-six consecutive video-recorded translabyrinthine operations at Gentofte Hospital, for tumors of 5 to 25 mm, were investigated for possible damage to the facial nerve from cauterization, suction, stretching, pushing, and other instrumental trauma at the following regions: fundus, internal meatus, porus, cerebellopontine angle, and brain stem. House-Brackmann grading of the postoperative facial nerve function was determined from the patient records for the 1st, 3rd, and 10th days and 3 months and 6 months postoperatively, as well as the final status. Suction on the nerve seems to be the most important factor for perioperative facial nerve damage. The most common site of damage was the porus region. This investigation shows thermic drilling lesions to be very relevant. There was no correlation between the degree and character of damage and the postoperative facial nerve function. In eight patients we cannot explain the postoperative facial palsy. PMID- 1416637 TI - Recovery from repeated sudden hearing loss with corticosteroid use in the presence of an acoustic neuroma. AB - Sensorineural hearing loss of sudden onset may be the presenting symptom in up to 14% of patients with acoustic neuroma. We present the first reported case of sudden hearing loss in an only hearing ear with recovery to normal levels after steroid therapy on four separate occasions. Evaluation revealed a 1.5-cm acoustic neuroma. After middle cranial fossa decompression, a fifth episode with recovery after steroid use was documented. A review of the recent literature is presented, emphasizing the possible causation of sudden sensorineural hearing loss with recovery to normal in patients with acoustic neuroma. Modalities of therapy for the dilemma of the acoustic neuroma in an only hearing ear are discussed, including surgery, radiotherapy, and chemotherapy. An aggressive approach to the evaluation of the cause of sudden hearing loss is suggested. PMID- 1416638 TI - Single motor unit activity of human intrinsic laryngeal muscles during respiration. AB - Individual motor units in the thyroarytenoid (TA) and cricothyroid (CT) muscles were studied in 10 normal human volunteers during quiet respiration. Both tonic and phasic firing patterns were found in both TA and CT units. The rate of firing was higher during inhalation than during exhalation in phasic TA units and in tonic CT units. Tonically active units had a higher firing frequency than phasically active units in both TA and CT muscles. Phasically active units corresponded with the respiratory cycle, with firing associated with inhalation in both the TA and CT muscles. A variety of firing patterns were found between units in both the TA and CT muscles, and in one subject, units recorded from the same muscle had very different firing patterns. The results suggest that although laryngeal motoneurons are modulated by the respiratory cycle, they do not respond uniformly to respiration. PMID- 1416639 TI - Histopathology of tubotympanum of children with otitis media treated with ventilation tubes. AB - We studied histopathologically the middle ear (ME) and eustachian tube (ET) in 12 temporal bones from eight children who had had otitis media with effusion that had been treated with ventilation tubes (VTs) for 3 weeks to 11 months. In the ME, 1) only a minimal amount of effusion was seen in most of the ears treated for 3 months or longer, 2) the severity of submucosal inflammation almost paralleled the amount of effusion, 3) the amount of granulation tissue on the tympanic membrane at the site of VT insertion also seemed to parallel the degree of ME inflammation, and 4) epidermal ingrowth was seen in both of the two ears treated with VTs for 10 and 11 months. Pathologic findings in the ET were generally more severe than those in the ME, but tended to decrease with longer VT therapy. In two ears with VTs obstructed by inflammatory granulomatous tissue, the entire ME cavity was filled with effusion, and dense effusion plugged the bony portion of the ET. The results of this study indicate that 3 to 11 months of treatment with a VT is effective for reversing the ME effusion and for reducing inflammation in the ME. Some inflammation may be left in the ET, however, even with 11 months of VT therapy, and epithelial ingrowth should be watched for when VT therapy lasts 10 months or longer. Despite the fact that most of our temporal bones were from infants and children who had a variety of systemic diseases or disorders and in whom their terminal event might have contributed to our findings, we consider these temporal bones to be informative. PMID- 1416640 TI - Immunologic response of adenoidal lymphocytes to respiratory syncytial virus. AB - Adenoidal lymphocytes obtained from 43 subjects with serum antibodies to respiratory syncytial virus (RSV) were established in culture in vitro and analyzed for immunoglobulin (Ig) and RSV-specific antibody synthesis. Spontaneous synthesis of Ig was consistently observed in culture supernatants. The ratios of IgA to IgG and IgM to IgG in adenoidal lymphocyte culture supernatant were higher than in serum. In cell cultures stimulated with RSV or pokeweed mitogen, RSV antibody activity was detected in 25 of 43 (58.1%) for IgG, 5 of 43 (11.6%) for IgA, and 4 of 43 (9.3%) for IgM. Also, RSV-specific IgG was detected in some supernatants from unstimulated cultures. In seven cases the cultures of autologous tonsillar lymphocytes were also investigated. Autologous organs exhibited similar polyclonal Ig production and RSV-specific antibody synthesis. These observations demonstrate that both adenoids and palatine tonsils are continuously engaged in synthesis of local antibodies to viral pathogens available to the nasopharynx and respiratory mucosa. PMID- 1416641 TI - Radiographic analysis of deep cervical abscesses. AB - Correlation of the radiographic examination and the clinical evaluation of deep cervical abscesses contributes to the surgical program for exposure and drainage. The deep cervical spaces are analyzed with reference to local anatomy, sources of infection, potential for lateral and vertical extension, and identification of regional expansion by standard and computed tomography. Guidelines and recommendations are proposed for clinical application and supported by illustrative cases. PMID- 1416643 TI - Aerobic bacteriology of chronic suppurative otitis media without cholesteatoma in children. AB - Medical management of chronic suppurative otitis media without cholesteatoma in children was shown recently to be efficacious. We undertook a prospective study in order to determine 1) the organisms associated with the disease and their sensitivity to various antibiotics and 2) their association with clinical variables. Pseudomonas was isolated from 84% of the patients, enteric gram negative bacilli from 32%, Staphylococcus aureus from 20%, streptococci from 14%, and Hemophilus influenzae from 15%. Pseudomonas aeruginosa was the sole isolate in 48 of the 128 patients (38%). The sensitivity of P aeruginosa (78 isolates) was 100% (of isolates) to mezlocillin and ciprofloxacin, 99% to tobramycin and ceftazidime, 97% to piperacillin, 94% to gentamicin, and 78% to ceftriaxone. The isolated organisms and their sensitivity to antibiotics were not associated with age, sex, duration of otorrhea, or the presence of granulation tissue or polyps. We believe that our data may contribute to the appropriate choice of antibiotics when nonsurgical management of chronic suppurative otitis media without cholesteatoma is considered. PMID- 1416642 TI - Junctional epidermolysis bullosa of the larynx. Report of a case and literature review. AB - Epidermolysis bullosa (EB) is a group of rare inherited disorders in which minor trauma causes blister formation in the skin and mucosa, including the esophagus. Morbidity varies with the type of disease and ranges from occasional trivial skin blisters to death in infancy. Laryngeal involvement presenting as hoarseness and respiratory distress has been reported in nine patients, five of whom had junctional EB. We present the sixth case of junctional EB with laryngeal involvement, and offer guidelines for otolaryngologists and anesthesiologists caring for these fragile patients. PMID- 1416645 TI - Rhinoscleroma and rhinosporidiosis. AB - For North American otolaryngologists, rhinoscleroma and rhinosporidiosis are moving more into the differential diagnosis of chronic inflammatory diseases of the upper airway, particularly the nasal cavity. This change is occasioned by the influx of immigrants from parts of the world to which the diseases are endemic. Diagnosis is established by identification of the causal organisms, the readily seen Rhinosporidium seeberi for rhinosporidiosis and the more elusive Klebsiella rhinoscleromatis for rhinoscleroma. PMID- 1416644 TI - Double aortic arch. AB - In conclusion, the diagnosis of DAA should be suspected in an infant with either biphasic stridor or feeding-related respiratory distress. Radiographic studies combined with appropriate thorough endoscopic evaluation should confirm clinical suspicion. Thoracotomy with surgical division of the DAA has given excellent long term results. PMID- 1416646 TI - Inhibition of nasopharyngeal colonization of Hemophilus influenzae by oral immunization. AB - Nontypeable Hemophilus influenzae organisms were inoculated into the nasopharynx of BALB/c mice immunized by oral administration of formalin-killed bacteria. Salivary antibodies and the colonization of H influenzae in the nasopharynx were investigated in order to clarify the effect of oral immunization. Salivary immunoglobulin A antibody titers against H influenzae were significantly increased by oral immunization, but salivary immunoglobulin G antibody titers were not. The bacteria inoculated into the nasopharynx were more rapidly eliminated in immunized mice than in control mice. The results suggest that oral immunization might be useful in preventing otitis media with effusion by inhibiting the colonization of the nasopharynx by pathogenic bacteria. PMID- 1416647 TI - Erythromycin inhibition of lipopolysaccharide-stimulated tumor necrosis factor alpha production by human monocytes in vitro. AB - The mechanism of clinical effectiveness of low-dose and long-term erythromycin (EM) treatment for diffuse panbronchiolitis, sinobronchial syndrome, and associated otitis media with effusion was investigated by studying the effects of EM on tumor necrosis factor alpha (TNF-alpha) production by cultured human monocytes stimulated with lipopolysaccharide. At concentrations of 0.1 microgram/mL or more, EM inhibited TNF-alpha release from human monocytes stimulated by lipopolysaccharide in a dose-dependent manner. Of the other macrolides tested, roxithromycin, an EM derivative, also showed significant inhibition of TNF-alpha production, whereas josamycin failed to inhibit TNF-alpha release from monocytes. Nonmacrolidic drugs such as minocycline hydrochloride, ofloxacin, or penicillin G had no significant effect on TNF-alpha production. These results suggest that the clinical improvement of chronic respiratory diseases by EM may depend on the suppression of production of inflammatory cytokines such as TNF-alpha. PMID- 1416648 TI - Immunologic characteristics of cytokines in otitis media with effusion. AB - Levels of cytokines, interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in samples of the middle ear effusions (MEEs) from 144 ears with otitis media with effusion (OME) by enzyme-linked immunosorbent assay, followed by cytologic analysis. Middle ear effusions of the acute purulent type contained a significantly higher concentration of cytokines compared with normal control sera (p < .001). Cytokines were observed at lower levels in MEE in adults than in children. Tests of children at the chronic stage of MEE showed higher levels of TNF than IL-1 and GM-CSF. Meanwhile, IL-1 beta showed significantly higher concentrations in acute purulent types than in serous and mucoid types (p < .01). In cytologic analysis, the mean level of IL-1 beta was significantly higher in the neutrophil-rich group than in other groups (p < .05). Cytokines possess several biologic properties, some of which are associated not only with acute otitis media but also with chronic otitis media. This study showed that cytokines, especially IL-1 beta, contribute to infiltration into the middle ear by inflammatory cells. This implies that the persistent presence of cytokines in MEE could be a factor in prolonged OME. PMID- 1416649 TI - Neutrophil elastase and its complex with alpha 1-antitrypsin in the pathogenesis of chronic suppurative otitis media. AB - Neutrophil elastase (NE) and its complex with alpha 1-antitrypsin were quantified in ear discharges from 15 patients with chronic suppurative otitis media (CSOM), and their levels were compared to those in middle ear effusions from 10 pediatric patients with chronic otitis media with effusion (OME). The localization of immunoreactive NE was also examined by immunocytologic study. The mean value of total NE was 161.8 +/- 29.5 micrograms/mL in CSOM, which was significantly higher than that in OME (16.5 +/- 6.7 micrograms/mL). The mean value of NE-alpha 1 antitrypsin complex was 13.7 +/- 8.8 micrograms/mL in CSOM and 7.8 +/- 4.0 micrograms/mL in OME. There was no significant difference between culture positive and culture-negative samples in CSOM. Immunoreactive NE could be observed in the neutrophils of ear discharges, and extracellular release of NE was also observed. Ear discharges in CSOM contain a considerable amount of uncomplexed NE, of which the level does not depend on active bacterial infections. Uncomplexed NE seems to play a role in the chronicity of CSOM. PMID- 1416650 TI - Interleukin-1 of cholesteatomatous keratinocytes. AB - Interleukin-1 (IL-1) has been thought to be one of the essential cytokines mainly produced by macrophages. It has recently been reported that epidermal keratinocytes produce IL-1, and attention is being paid to local immune reactions mediated with this cytokine. Interleukin-1 not only activates lymphocytes, but also acts as an osteoclast-activating factor. In this study, we used immunohistochemistry and immunoblotting on cholesteatomatous epithelium with anti IL-1 alpha antibody and anti-IL-1 beta antibody. Next, the relationship of cholesteatomatous debris to the production of IL-1 by keratinocytes was evaluated. Highly concentrated IL-1 alpha was found in the cholesteatomatous epithelium, especially in the basal cell layer. The intensity of IL-1 beta staining was weaker than that of IL-1 alpha staining. In the immunoblotting study, the 31 kd band, an intracellular immature precursor molecule, was identified. The production of IL-1 alpha from keratinocytes was augmented to a greater degree by cholesteatomatous debris than by lipopolysaccharide or keratin. The keratinocytes did not produce IL-1 beta. These findings suggest that IL-1 alpha is derived from cholesteatomatous keratinocytes. Interleukin-1, mainly IL-1 alpha, from the stimulated cholesteatomatous keratinocytes may be an important factor in the markedly increased bone resorption observed in cholesteatoma. PMID- 1416651 TI - Distribution of immunocompetent cells in the endolymphatic sac. AB - To better understand the role of immunocompetent cells in the defense mechanism of the inner ear, the distribution patterns of those cells were investigated in the endolymphatic sac (ES) of mice maintained in three different conditions: germ free (GF), specific pathogen-free (SPF), and conventional (CV). In another experiment, the recruitment of lymphocyte subsets was examined in the ES of SPF rats undergoing a perilymphatic antigen challenge after systemic presensitization. In the ES of GF mice, no immunocompetent cells were found. In the ES of SPF and CV mice, cells positive for IgG, IgA, IgM, and Lyt-1 were present in much smaller numbers than in the nasal mucosa. Cells positive for Lyt 2 were not seen in the ES of any mice. In the ES of rats that underwent a perilymphatic antigenic stimulation after a systemic presensitization, B lymphocyte subsets (positive for IgG, IgA, IgM) were mobilized in increased numbers, and T cell subsets (helper/inducer and suppressor) were also found 1 week after perilymphatic antigen challenge. These results taken together suggest that the ES is not originally equipped to possess immunocompetent cells and mount an immune response, but that once it has been activated with the inner ear antigenic stimuli, the ES can be the active site of a local immune response of the inner ear. PMID- 1416652 TI - Pathogenesis of experimental otitis media with effusion caused by a combination of eustachian tube dysfunction and immunosuppression. AB - Inflammatory factors appear to play an important role in the development of otitis media with effusion (OME). However, otitis media experimentally induced by endotoxin injection or secondary immunoresponse was not persistent. In order to produce refractory OME, two pathologic conditions were necessarily combined: tubal ventilatory dysfunction and suppression of the immunologic defense mechanism by immunosuppressive drugs. In the presence of these two pathologic conditions, all cases that evidenced negative middle ear pressure due to tubal dysfunction developed OME. In the control group with either tubal dysfunction or immunosuppression alone, only 1 of 20 ears developed OME. Transtubal infection due to negative middle ear pressure caused by tubal ventilatory dysfunction may be one of the most important etiologic factors in OME. PMID- 1416653 TI - Endolymphatic hydrops induced by immune response of the endolymphatic sac: relation to perilymph antibody levels. AB - This study investigated the effect of a secondary immune response in the endolymphatic sac on the development of endolymphatic hydrops in guinea pigs. Following secondary keyhole limpet hemocyanin (KLH) challenge directly to the sac in systemically presensitized animals, hydrops rapidly developed within 1 week, then gradually reduced by 4 weeks. After 5 weeks, hydrops gradually recurred and developed again. Mean perilymph anti-KLH antibody levels rose from day 1 to 4 weeks and then decreased. The elevation of perilymph anti-KLH antibody levels on day 2 was due to an increased vascular permeability and there was a local regeneration by the challenge of the sac after day 7. The development of hydrops correlated well with mean perilymph anti-KLH antibody levels in the period from day 1 to day 7. After 2 weeks, there was no correlation between them. These results suggest that an immune response of the sac may induce an excess secretion of endolymph in the initial stage and may further lead to irreversible dysfunction of the sac at a later stage. PMID- 1416654 TI - Vestibular disorders following immune response of the endolymphatic sac in the guinea pig. AB - The effect of a direct antigen challenge to the endolymphatic sac on vestibular function was investigated in guinea pigs. Following keyhole limpet hemocyanin (KLH) challenge to the sac in systemically presensitized guinea pigs, caloric responses were examined in 18 animals on days 1, 7, 14, 21, and 28. Caloric responses were significantly suppressed in 13 animals by day 7; of these, 5 animals had recovered by day 14 and 8 animals had not yet recovered by day 28. The behavior of spontaneous nystagmus was examined every hour in 10 animals at intervals of 3 to 56 hours after sac challenge. Irritative spontaneous nystagmus preceding paralytic nystagmus appeared in 5 animals, for which the mean onset was 14.6 +/- 3.1 hours and the mean duration was 4.4 +/- 6.5 hours. Paralytic spontaneous nystagmus appeared in all animals, for which the mean onset time was 23.3 +/- 12.3 hours. Neither direct KLH primary challenge of the sac nor phosphate-buffered saline injection to the sac caused significant changes in the vestibular function. These results suggest that an immune response of the sac induces a vestibular disorder and may produce an attack of vertigo similar to that of Meniere's disease. PMID- 1416655 TI - Localization of type IV collagen and laminin in the guinea pig inner ear. AB - The distribution of type IV collagen (C-IV) and laminin, which are important components of the basement membrane (BM), was studied immunohistochemically in the inner ear of healthy Hartley guinea pigs. Antibodies against C-IV and laminin were used in this study. The distribution of C-IV in the inner ear was almost the same as that of laminin, but the extent of staining for laminin was less than that for C-IV in some sites. The sites of the inner ear in which these components were most densely localized were the areas surrounding the spiral ganglion cells and nerve fibers, the capillary vessels in the stria vascularis and the spiral prominence, and an area directly beneath the epithelium of the endolymphatic sac. Type IV collagen and laminin were also localized around the other vascular BM and the epithelial BM in the inner ear, but the tectorial membrane, the cupula of the crista ampulla, and the sensory epithelium did not take up stain. These results suggest that the vascular BM of the stria vascularis and spiral prominence, as well as the epithelial BM of the endolymphatic sac, may play an important role in fluid transport, and that the perineural BM of the inner ear might play an important role in the functional maintenance of the optimal environment of the inner ear nervous system. PMID- 1416656 TI - Alterations of charge barrier in the inner ear following immune reactions. AB - We investigated electron microscopically the changes of anionic sites of a charge barrier in the capillary basement membrane of the stria vascularis and endolymphatic sac following inner ear immune reactions. Hartley guinea pigs were immunized with bovine type II collagen, keyhole limpet hemocyanin, or horseradish peroxidase, with boosted and challenged antigens through the stylomastoid foramen. Animals were killed painlessly from several days up to 56 days after the antigen challenge. Polyethylenimine was used as a cationic tracer in order to observe the localization of anionic sites of the charge. In the animals immunized with bovine type II collagen or horseradish peroxidase, a significant decrease of anionic charge in the stria and the sac was found in the early stage of immunization. However, the keyhold limpet hemocyanin immunization group did not show any remarkable changes in the charge because of its lesser transfer into the inner ear due to of its high molecular weight and negative surface charge. A decrease of the charge under immunologic conditions may induce a hyperpermeability of vessels and a malabsorption of endolymph, and thus may cause endolymphatic hydrops. PMID- 1416657 TI - Detection of genomic sequences of respiratory syncytial virus in otitis media with effusion in children. AB - The reverse transcriptase-polymerase chain reaction and the nested polymerase chain reaction were used for detection of respiratory syncytial virus (RSV) sequences in middle ear effusions collected from children with otitis media. Sequences of RSV were detected in 21 of 34 samples tested. These samples were collected during and/or after natural outbreaks of RSV infection in the community. In those patients from whose nasopharynges RSV was isolated, the viral sequences were highly detectable (75%) in the effusions. These observations suggest RSV as an important factor in the pathogenesis of otitis media with effusion. PMID- 1416658 TI - Mechanism of immune complex-mediated inner ear diseases. AB - Tissues of the stria vascularis of normal rabbits were collected as cochlear antigen and injected into the foot pad of guinea pigs. The mechanism of development of endolymphatic hydrops was studied by the tracer method. Damage to the capillary endothelium and an increase in vascular permeability were found in the stria vascularis. Therefore, we studied patients with a raised level of immunoglobulin (Ig) G-class circulating immune complexes (CICs). Hearing loss was found in 3 of 22 patients with significantly elevated IgG CIC levels (13.6%). The relationship between inner ear disease and the presence of CIC was considered to be very significant. The possible mechanism of CIC-mediated inner ear diseases is discussed. PMID- 1416659 TI - MRL/MP-lpr/lpr mouse as a model of immune-induced sensorineural hearing loss. AB - Hearing acuity and inner ear disorders of MRL/lpr mice, bred for the study of autoimmune disease, were examined in comparison to those of BALB/c mice. The auditory brain stem response threshold of 20-week-old MRL/lpr mice was significantly higher than that of BALB/c mice of the same age (p < .01). The pathologic changes of 20-week-old MRL/lpr mice were characterized by the degeneration of intermediate cells, widened intercellular spaces, and immunoglobulin G deposition on the basement membrane of strial blood vessels as well as in the basal infolding of strial marginal cells, which were absent in BALB/c mice. That there were no other evident pathologic findings in the cochlea or middle ear suggests that these changes in the stria vascularis seemed to be responsible for the sensorineural hearing loss of this mouse. The MRL/lpr mouse was thought to be a good experimental model to study the spontaneous sensorineural hearing loss caused by an immune reaction. PMID- 1416660 TI - Cochlear and renal pathology in the autoimmune strain mouse. AB - This study was designed to investigate the role of immunologic mechanisms in sensorineural hearing disorders and the relationship between inner ear and renal disorders. Autoimmune strain (NZB/kl) mice, in which autoimmune disease can be spontaneously induced, were used in this study. The mice were tested for acoustic brain stem responses, cochlear and renal disorders, and circulating immune complex serology by means of enzyme immunoassay. Pathologic studies consisted of observation of tissue changes following hematoxylin and eosin staining and indirect immunofluorescence staining under light microscopy. Compared to controls, the hearing was impaired in NZB/kl mice. Indirect fluorescence staining showed immunoglobulin G deposits in the stria vascularis. There was a correlation between the degree of hearing impairment and the severity of stria vascularis lesions. The NZB/kl mouse can provide a model for sensorineural hearing disorders secondary to immunologic disorders. PMID- 1416661 TI - [Pustular dermatoses in the neonatal period]. AB - The diagnosis of pustular dermatosis occurring during the first months of life is usually based on clinical findings. However, some cases may require a few simple investigations including cytological studies, cultures, and skin biopsies. The most common causes of infectious pustular skin lesions include bacterial infections, which may be septicemic (with Listeria as the leading causative agent) or initially localized (staphylococcus); viral infections (varicella, herpes); fungal infections, i.e., candidiasis (congenital or neonatal) or the very recently described form of pustulosis due to Malassezia furfur; or parasitic (scabies). The main benign transient neonatal forms of pustulosis include infantile acropustulosis (for which the relationship with scabies is discussed), toxi-allergic erythema, transient pustular melanosis, and neonatal acne. Lastly, rare causes of neonatal pustulosis are reviewed. The need for investigating every neonate with skin pustules for an infectious disease, especially due to a bacterium, is emphasized. PMID- 1416662 TI - [Oculocutaneous albinism]. AB - Oculocutaneous albinism (OCA) is an inherited condition characterized by hypopigmentation of the skin, hair, and eyes. Ocular involvement is often severe with photophobia, decreased visual acuity due to foveal hypoplasia, nystagmus, and strabism secondary to defective routing of optic axons in the chiasma. Cutaneous hypopigmentation is responsible for diminished photoprotection that places patients at increased risk for skin cancers. OCA also occurs in a number of life-threatening conditions, including Hermansky-Pudlak syndrome, Chediak Higashi syndrome, and Griscelli-Prunieras syndrome. Most cases of OCA are inherited on an autosomal recessive basis. Several mutations have recently been identified in type I OCA or "tyrosinase-negative" OCA. Identification of other genetic abnormalities will probably occur in the future and will lead to more accurate classification of OCA syndromes. PMID- 1416663 TI - [Panniculitis in children]. AB - Panniculitis is an inflammation of subcutaneous fat responsible for fairly uniform clinical features including nodules, plaques or swelling located in the subcutaneous tissue, occasionally progressing to atrophy of subcutaneous fat. Some forms of panniculitis specific of childhood are responsible for readily recognizable clinical patterns. Examples include acute neonatal fat necrosis, sclerema neonatorum, cryopanniculitis, steroid-induced panniculitis, and toxoplasmosis-related multinodular fat necrosis of Royer syndrome. With the exception of erythema nodosum, the cause of panniculitis is identified upon histologic examination of a deep skin biopsy which ensures the differentiation of infectious nodules, vasculitis nodules, and apparently primary forms of nodular panniculitis fitting the description of Weber-Christian syndrome, Rothmann-Makai syndrome, histiocytic cytophagic panniculitis or lupus panniculitis. PMID- 1416664 TI - [Allergic vasculitis in children]. AB - Allergic vasculitis is characterized clinically by vascular purpura and histologically by leukocytoclastic angiitis of the small vessels in the middle and superficial dermis. Extra-cutaneous lesions may occur. Among them, the most common are joint manifestations. Renal involvement governs the prognosis. Circulating immune complexes probably contribute to the development of lesions, although this role has not been firmly established. Cellular immunity is probably also involved. A large number of factors may trigger the development of allergic vasculitis. Clinical patterns vary widely across patients. In 50% of patients no cause is identified. In children, Henoch-Schonlein purpura and infections (viral or bacterial) are the most common "causes". The ideal treatment would be elimination of the causative allergen. However this is often impossible to achieve and a variety of symptomatic treatments (rest, dapsone, colchicine, corticosteroids, immunosuppressants...) may be discussed according to the severity of clinical manifestations. Effectiveness of these treatments is variable. PMID- 1416665 TI - [Kasabach-Merritt syndrome in children]. AB - Kasabach-Merritt syndrome is a combination of thrombocytopenia, intravascular coagulation, and a rapid increase in the size of an angioma. Anemia and disseminated intravascular coagulation may develop. This infrequent syndrome is severe and may be life-threatening. Pathophysiologic mechanisms underlying the condition are incompletely understood and, consequently, many different treatments are used, including systemic corticosteroids, compression, embolization, antifibrinolytic agents, platelet aggregation inhibitors, irradiation, and others. From findings in eight personal cases, the authors review clinical and biological features, pathophysiologic hypotheses and therapeutic strategies. PMID- 1416666 TI - [Gangrenous ecthyma of the diaper area in infants]. AB - Ecthyma gangrenosum due to Pseudomonas aeruginosa is a skin infection in which necrotic ulcerations surrounded by a red areola develop. The diaper area is the region most often involved in infants. Typically, ecthyma gangrenosum occurs in patients with septicemia and risk factors (chemotherapy, neutropenia). However, transient bacteremia or an infection confined to the skin may be the cause in some patients, with maceration in the diaper area and previous antibiotic therapy as risk factors. PMID- 1416667 TI - [Cutaneous lesions in the orofaciodigital syndrome]. AB - The term OFD syndrome designates a group of heterogeneous clinical patterns of which seven different types have been described. Type I, or Papillon Leage syndrome, is the most common pattern and the only type in which skin lesions occur. Type I OFD is a sex-linked dominant disorder. Two cases of OFD Type I with cystic lesions of the face are reported herein. The second patient also had polycystic kidneys. This combination has already been reported previously and all children with OFD should be investigated for polycystic kidney disease. PMID- 1416668 TI - [Menkes syndrome. An unusual pigmentation anomaly in a mother and three sisters]. AB - Menkes syndrome is a sex-linked recessive disease. The authors previously reported a case in a boy whose neurologic condition deteriorated gradually until death occurred at the age of seven and a half months. Diagnosis was confirmed by the finding of very low plasma levels of copper and ceruloplasmin. Evaluation of family members disclosed hypopigmentation of one half of the abdomen in three sisters and in the carrier mother. This hypopigmentation may be ascribed to decreased melanocyte copper-dependant tyrosinase activity. Among cells in the body, this anomaly may be present or absent according to whether or not the abnormal X chromosome is inactivated. PMID- 1416669 TI - Laparoscopic cholecystectomy. PMID- 1416670 TI - On camera--not in camera. PMID- 1416671 TI - Laparoscopic cholecystectomy: the first 155 patients. AB - Laparoscopic cholecystectomy has been attempted in 155 patients. Eight patients required conversion to open cholecystectomy (5%): three owing to lack of clear anatomical detail, two procedures were abandoned because of instrument failure, two had a dilated common bile duct on cholangiography, and one owing to a very adherent mucocele of the gallbladder. Cholangiography was performed selectively; successfully completed in 45 (22% of all patients). Common bile duct stones were found in two patients. All patients were drained, with two bile leaks, one requiring a laparotomy. There was one ductal injury. Most patients (85%) were discharged within 48 h. This initial experience suggests laparoscopic cholecystectomy is the procedure of choice for most patients with symptomatic cholelithiasis. PMID- 1416672 TI - Laparoscopic laser cholecystectomy: results of the technique in 210 patients. AB - The results of laparoscopic laser cholecystectomy (LLC) in a consecutive series of 210 patients, operated on between May 1990 and August 1991, were assessed to analyse the advantages of the technique and to detail the causes of any technical problems, failures, or complications. The operations were performed by JMcKW and ADNS. A success rate of 98% (206/210) was achieved with a minor complication rate of 13% (26/210) and major complication rate of 3% (7/206), including three patients (3/206; 1.5%) who had a reactionary haemorrhage postoperatively, two requiring laparotomy. The length of hospital stay was 48 h or less in over 80% (148/184) of the patients. The period of absence from work was 2 weeks or less in over 90% (118/130) of the patients. Cholecystectomy can safely be performed laparoscopically and this procedure has significant advantages over open cholecystectomy. PMID- 1416673 TI - Laparoscopic laser cholecystectomy: our first 200 patients. AB - A series of 200 consecutive patients were considered for laparoscopic laser cholecystectomy. Laparoscopic laser cholecystectomy was attempted in 195 cases and was performed in 192 cases. Laparoscopy was performed in five patients, but laparoscopic cholecystectomy was not attempted owing to dense adhesions (3), cholangiocarcinoma (1) and an absent gallbladder (1). The indications for operation were symptomatic gallstones which included biliary colic (142), acute cholecystitis (49) and gallstone pancreatitis (9). The median duration of operation was 75 min. Operative cholangiography was attempted in 151 (77%) of cases, and was successful in 85% of attempts. Laparoscopic common bile duct visualisation was performed three times with successful stone extraction twice. The other common bile duct was normal. The median duration of postoperative hospital stay was 2 days, for return to normal activity 6 days, and for return to work 10 days. Mean analgesic and antiemetic requirements were approximately one third of those for open cholecystectomy. Of the patients, 94% reported good or excellent overall satisfaction and 96% reported excellent cosmetic results. Seven complications occurred (4%). Three patients had immediate conversion to laparotomy owing to haemorrhage (2) and gallbladder rupture (1). Four patients required laparotomy for postoperative complications (common bile duct damage, slipped clips from cystic duct, perforated duodenum and leaking accessory hepatic duct). No complications occurred in the last 140 cases. These data suggest that laparoscopic laser cholecystectomy reduces the discomfort of laparotomy and allows a shorter postoperative recovery. The operation has a learning curve, but will ultimately be applicable to the majority of patients with symptomatic gallstones. PMID- 1416674 TI - Can cholangiography be safely abandoned in laparoscopic cholecystectomy? AB - The introduction of laparoscopic cholecystectomy, improvements in ultrasound technology and the success of endoscopic sphincterotomy have raised new questions regarding the role of intraoperative cholangiography. Our aim was to analyse the ability of preoperative clinical and ultrasound assessments to detect common duct stones in 86 patients with symptomatic cholecystolithiasis who then underwent cholangiography after percutaneous cholecystolithotomy. Six patients gave a history suggestive of common duct stones (either jaundice, cholangitis or pancreatitis). Ultrasound showed a dilated common duct in four patients (normal < 6 mm), and one of these had a stone demonstrated in the duct. The latter patient and one other with a dilated common duct had stones on cholangiography (which were extracted at ERCP), no stones were demonstrated in the other two. Ultrasound correctly identified common duct stones in two and excluded common duct stones in four others with a history suggesting the presence of stones. For patients undergoing laparoscopic cholecystectomy we would advocate the use of preoperative ultrasound instead of intraoperative cholangiography, and that endoscopic retrograde cholangiopancreatography is performed in the small number of patients shown to have a dilated duct or common duct stone. PMID- 1416675 TI - Laparoscopic operative cholangiography: a simple, successful, cost-effective method. PMID- 1416676 TI - An unusual complication of laparoscopic cholecystectomy. PMID- 1416677 TI - A cheap laparoscopic surgery trainer. PMID- 1416678 TI - Laparoscopic tube gastrostomy. AB - A laparoscopic approach to fashioning a permanent mucosal gastrostomy is described for the first time. It has a place in patients in whom endoscopic or radiological placement is impractical. PMID- 1416679 TI - Use of the hepatic arterial circulation for renal revascularisation. AB - Renal artery stenosis is increasingly being diagnosed as a cause of hypertension and renal impairment. Surgical intervention can restore function and improve hypertension in selected cases. Over a 42 month period, 12 patients with atherosclerotic renovascular disease underwent surgical revascularisation using the hepatic arterial circulation. All had disease of both renal arteries and 11 had some degree of renal impairment, with five requiring dialysis before operation. There were two deaths within 30 days of operation, eight patients had improved renal function after operation and three of the patients previously on dialysis became dialysis free. The hepatorenal method of renal revascularisation is described and its advantages discussed. PMID- 1416680 TI - Consequences of immediate failure of percutaneous transluminal angioplasty. AB - Percutaneous transluminal angioplasty (PTA) is often used for patients who would not previously have been treated, due for example, to their poor general condition or their symptoms being relatively mild. The approximate overall initial success and complication rates are 80% and 10%, respectively. Iliac angioplasties fare rather better than superficial femoral dilatations. There is little information on the outcome of those patients in whom the procedure cannot be completed satisfactorily or who have complications. From 1985 to December 1990, 318 PTAs have been attempted on our unit, the majority within the last 3 years. In 53 (17%) the dilatation was not carried out, due to inability to position the guidewire (31) or balloon (16) satisfactorily, to disease progression (3) or systemic problems (3). None of these patients was made worse and 10 subsequently had a successful angioplasty. Complications occurred in 28 (9%). These included distal embolisation (10), bleeding (9), dissection (1), thrombotic occlusion (4) and vessel rupture (4). Complications were more common after superficial femoral, compared with iliac angioplasty (P < 0.02, chi 2 test). Eight patients with occlusion or embolus were treated with thrombolysis, five successfully. Three of these patients, and seven others, had surgical intervention (three within 6 h of angioplasty). Ten patients were treated conservatively, one died. Of the 28 patients who sustained complications, 27 were improved compared with their status before angioplasty, once their complication had been dealt with. PTA is a generally safe procedure and when complications occur most can be dealt with effectively. PMID- 1416681 TI - Quality of life of octogenarians after aneurysm surgery. AB - Abdominal aneurysm repair in octogenarians is controversial. To justify surgery, survival with a reasonable quality of life is required. Between 1980 and 1988, 34 octogenarians underwent aortic aneurysm surgery (14 elective, 20 emergency). Of the 21 survivors, 20 were interviewed to determine their quality of life. At the time of interview the patients had a median survival of 19 months (range 4-67 months). Twenty age/sex matched normal patients, from the same GP population, were interviewed for comparison. A structured questionnaire was used to assess: physical mobility, activities of daily living, sleep and emotional problems. A symptom survey was also performed. The survival trend of elective patients was similar to that of a demographically similar 'normal' population. The survival trend of emergency patients returned to 'normal' after the first postoperative month. Quality of life of the 20 patients was comparable to the lifestyle enjoyed by normal subjects. Of the 20 patients interviewed, 18 had returned home after surgery. Elective and emergency aortic aneurysm surgery can be performed with reasonable survival and a good quality of life, and therefore cannot be denied to octogenarians on the basis of age alone. PMID- 1416682 TI - Is antibiotic penetration compromised in the ischaemic tissues of patients undergoing amputation? AB - Antibiotic prophylaxis is indicated for patients undergoing amputation for severe ischaemia or gangrene. However, the adequacy of tissue levels of antibiotics in ischaemic tissue is not known. In this study the serum and tissue antibiotic levels were measured after intravenous administration of metronidazole (15 mg/kg body weight) and cephradine (20 mg/kg body weight). In 11 patients, venous samples were taken at time 0 (induction of anaesthesia) 10, 30 and 60 min. Samples of 2 g each of fat and muscle were collected from the amputation site and three distal sites. Metronidazole and cephradine levels were measured and the degree of limb ischaemia estimated preoperatively by an isotope limb blood flow method. Our results indicate that both metronidazole and cephradine penetrate ischaemic tissues to levels equivalent of a Mean Inhibitory Concentration (MIC) 50 for most organisms encountered in vascular surgery, and that the degree of ischaemia does not alter this. PMID- 1416683 TI - The diagnosis of soft tissue tumours. AB - We prospectively analysed methods of diagnosis in 118 patients referred for definitive treatment with documented or presumed soft tissue sarcoma (STS). Of 65 patients with primary STS, 54 were biopsied before referral. Of these, 5 (9%) were biopsied by Tru-cut biopsy, 17 (32%) by incisional biopsy and 32 (59%) by excisional biopsy. The remaining 11 patients with primary STS, referred without biopsy, were all diagnosed by Tru-cut biopsy. An additional eight patients suspected of having STS were referred without biopsy and were found to have malignant tumours other than STS involving soft tissue by Tru-cut biopsy. Nineteen patients were proved to have benign soft tissue tumours; in 13 presumed to have STS, the diagnosis was unknown at referral. In four of these, biopsy was inappropriate. Of nine submitted to Tru-cut biopsy, an unequivocal diagnosis was made in 5 (56%) and incisional biopsy was required in the other four. Therefore, paradoxically, benign soft tissue tumours may be more difficult to diagnose with Tru-cut biopsy than malignant tumours. This study confirms the high degree of accuracy of Tru-cut biopsy in diagnosing malignant soft tissue tumours and highlights the disadvantages of open biopsy techniques. PMID- 1416684 TI - A simple scoring system to reduce the negative appendicectomy rate. AB - In a controlled, prospective study the following five criteria were used for the diagnosis and management of acute appendicitis: abdominal pain; vomiting; right lower quadrant tenderness; low grade fever (< or = 38.8 degrees C); and polymorphonuclear leucocytosis (TC > or = 10,000 with polymorphs > or = 75%). The aim of the study was to reduce the negative appendicectomy rate. If four out of five or five out of five criteria were present on admission, appendicectomy was carried out. On the other hand, if three out of five criteria were present on admission, the patient was subjected to active inpatient observation until either the development of the fourth criterion, when appendicectomy was performed, or until the patient recovered and the condition did not progress beyond the third criterion. Generalised peritonitis due to a perforated appendix was excluded from the study. Over a 1-year period, 58 patients (M:F = 45:13) were entered into the study. Appendicectomy was carried out in 46 (80%) of patients; of these, 32 patients (70%) were operated on soon after admission. The remaining 14 (30%) were operated on after a period of inpatient observation decided the development of the fourth criterion. A total of 12 patients (12/58 = 20%) did not undergo operation. The control group consisted of 59 patients upon whom appendicectomy was carried out by another surgical unit over the same 1-year period. The negative appendicectomy rate in the trial group was 6.5% (3/46), whereas in the control group it was 17% (10/59) (P < 0.05). We conclude that the use of a simple scoring system can significantly reduce the negative appendicectomy rate. PMID- 1416685 TI - Measuring outcome of total knee replacement using quality of life indices. AB - A series of 26 patients was studied before and after total knee replacement to determine the change in their quality of life, expressed as a gain in Quality Adjusted Life Years (QALYs). Global health status was assessed using the Nottingham Health Profile, disability by the Harris scale, pain by the McGill Pain Questionnaire, and anxiety and depression by the Hospital Anxiety and Depression Scale. Substantial reductions were found in pain, anxiety and depression, and a significant improvement was found in mobility. These data were used to generate a 'QALY' (Quality Adjusted Life Year) comparable to the measure used by Williams (1) in his comparative evaluation of medical and surgical treatments. A gain of only 0.42 QALY was found for knee replacement, which is about one-tenth the figure given by Williams for hip replacement. The difference appears to be attributable not to differences in the success of the operations, but rather to the scope that QALY calculations give for allocating comparable patients to different quality of life states. Tighter criteria are needed if QALYs are to be used to guide resource allocation. PMID- 1416686 TI - Changing patterns of colorectal cancer in a regional teaching hospital. AB - A study was performed of all patients who underwent either surgery or endoscopic polypectomy for colorectal cancer in Oxford between 1979 and 1983 to ascertain whether any changes had occurred in presentation, diagnosis, treatment or outcome since a previous study from the same centre undertaken between 1966 and 1971. The average number of patients treated annually had increased from 52.8 to 103.4. The growth of the population of the health district was 6.7%. A similar proportion (25%) continued to present as emergencies. There was an improvement in the proportion of cases presenting with Dukes' A and B lesions (54% vs 41%) (P < 0.001), and a decrease in the number of patients with extranodal disease (from 30.4% to 13.3%) (P < 0.001). Only 13.9% of patients underwent colonoscopy before surgery and 14 patients were treated by endoscopic removal alone. In a health district with a slowly growing population, the number of patients presenting with colorectal cancer had increased dramatically over a decade. Colonoscopy has so far made little impact on making an earlier diagnosis. The increase in colorectal cancer has important implications for resource allocation. PMID- 1416687 TI - Injuries related to wind speed. AB - This is a retrospective study of the injuries caused by high wind speeds during the storms of early 1990. Injured patients seen on windy days were compared with those seen on a group of control days. It was found that high wind speeds were associated with an increased risk of injury, especially when wind gusts exceeded 60 knots. This apparent wind speed threshold, above which injury is more likely, corresponds to the curve used by the Meteorological Office to predict wind related structural damage. It is postulated that this finding may be of use in assisting the Government in formulating its guidelines on when to warn the public that it is unsafe to venture out. PMID- 1416688 TI - Combined surgical audit by microcomputer involving units in four health regions. PMID- 1416689 TI - Urological complications of renal transplantation: the impact of double J ureteric stents. PMID- 1416690 TI - Bupivacaine instillation after herniorrhaphy. PMID- 1416691 TI - Anatomical repair of large incisional hernias. PMID- 1416692 TI - Intra-arterial thrombolysis should be the initial treatment of the acutely ischaemic lower limb. PMID- 1416693 TI - Cutaneous perianal recurrence of cancer after anterior resection using the EEA stapling device. PMID- 1416694 TI - Angiomyolipoma of the kidney: a clinical enigma in diagnosis and management. PMID- 1416695 TI - Vascular surgical training in the UK and Ireland. AB - Fifty-six vascular surgical trainees and 31 recently appointed consultants with an interest in vascular surgery replied to a postal questionnaire about their training. The majority fulfilled the guidelines recommended by the Vascular Advisory Committee of the Vascular Surgical Society of Great Britain and Ireland, which are--a minimum two years of higher surgical training in units with an interest in vascular surgery and a substantial and comprehensive experience of (operative) vascular surgery. However, the operative experience during training was very variable, ranging between 10 and 574 operations reported by new consultants. Minimum standards of operative experience may need to be defined. The survey also identified that training in carotid endarterectomy is sometimes deficient and noted that as much as one-third of operative experience may be gained 'out of hours' on emergency cases. To obtain this experience trainees have to work very long hours, two-thirds of senior registrars have vascular on call rotas of 1:2 or less. Imminent changes in the structure of higher surgical training and the reduction in hours worked by junior doctors may seriously affect vascular surgical training. PMID- 1416697 TI - Glove punctures and wet gowns: no room for complacency. PMID- 1416696 TI - Appropriateness of cholecystectomy: the public and private sectors compared. AB - OBJECTIVE: To investigate the appropriateness of cholecystectomies undertaken in the public and private health sectors. DESIGN: Retrospective case note review using the findings of two consensus panels. SETTING: 35 consultant surgeons working for North West Thames Regional Health Authority and in the private sector. PATIENTS: 269 patients undergoing cholecystectomy during the study period, of whom 17 were excluded because there was insufficient information available. MAIN OUTCOME MEASURES: Appropriateness ratings as assessed by two consensus panels, one composed of surgeons and one mixed, containing doctors from different specialties. RESULTS: The mixed panel would have rated 41 per cent of cases appropriate, less than 1 per cent equivocal and 30 per cent inappropriate. The remaining 29 per cent had indications about which the panel did not reach agreement. The surgical panel would have rated 52 per cent appropriate, 3 per cent equivocal and 2 per cent inappropriate. The remaining 44 per cent had indications about which the panel did not reach agreement. Most of the patients who would have been rated inappropriate had vague symptoms only. There were no significant differences between the NHS and private patients as regards their appropriateness. NHS patients were more likely to have more than one ultrasound and to be operated on as an emergency. CONCLUSIONS: An appreciable proportion of patients undergo cholecystectomy for indications which were deemed inappropriate by a mixed panel, but not a surgical panel. Variation in clinical judgement is an important factor in the decision to operate--44 per cent of cases had indications, the appropriateness of which the surgical panel were undecided about. There were no significant differences between NHS and private patients as regards the appropriateness of their indications. These findings need to be confirmed by further studies comparing the public and private sectors. PMID- 1416698 TI - Glove perforation during surgery: what are the risks? AB - Surgical gloves are important in protecting medical staff from exposure to pathogens during surgery, especially viruses such as hepatitis B and the human immunodeficiency virus. We have studied the incidence and circumstances of surgical glove perforation using a sensitive electronic device. The glove perforation rate during elective general surgery was compared with that seen during an anastomosis workshop, where surgical trainees operated in a laboratory setting. A total of 220 gloves were tested for perforations pre- and postoperatively during general elective surgical procedures. During the surgical training workshop 72 gloves were tested. Fifty-two gloves (24%) were perforated during surgical procedures. Among surgeons, consultants had a significantly lower perforation rate than trainees (26% vs 46%, P < 0.05, chi 2), that for assistants was much lower (9%). The perforation rate for scrub nurses was surprisingly high at 22%. Glove perforation among trainees was significantly lower during workshop procedures than at elective surgery (17% vs 46%, P < 0.05, chi 2), probably because glove perforation occurs commonly at wound closure. Glove perforation remains very common, particularly among surgical trainees. Glove perforation should be reduced by teaching better techniques, especially 'no-touch', particularly for wound closure. PMID- 1416699 TI - Hazards to surgeons in trauma and elective orthopaedic surgery: use of an electronic device to warn of intraoperative glove perforations. AB - An electronic device intended to detect glove punctures as they occur peroperatively has been described previously. This study reports the experience of its use in 80 orthopaedic cases. The device detected all punctures, except one, where fluid could have contacted the surgeon's hand (n = 16). Wet gowns and drapes are potential routes for transmission of pathogens, and were responsible for the alarm sounding on 30 occasions. This device can minimise the exposure to potentially hazardous body fluids when glove punctures are not clinically apparent. PMID- 1416700 TI - Alcohol-related hand injuries: an unnecessary social and economic cost. AB - Severe hand injuries constitute the largest number of acute referrals to this plastic surgery unit, the admission of these patients often displacing routine admissions due to bed shortages, thus increasing waiting list time. This study showed that a high percentage of these injuries were alcohol-related and were therefore preventable. The economic cost to the unit is discussed. PMID- 1416701 TI - Non-tumour morbidity and mortality after modified radical mastectomy. AB - From 1985 to 1987 148 patients underwent mastectomy for breast cancer, of whom 91 underwent modified radical mastectomy. Of these patients (median age 60 years (range 31-86 years)), 89 have been assessed for early (< 30 days) and late (> 30 days) non-tumour morbidity and mortality. A total of 41 patients had nodal metastases. Adjunctive therapy used was tamoxifen in 70 patients and radiotherapy in 20. Overall, 47 patients (53%) developed a total of 75 complications, and there was one 30-day mortality. Of the patients, 26 developed one complication, 14 had two complications and 7 three complications. Early complications were lymphocoele/seroma (n = 22), wound infection (n = 9) and cardiopulmonary problems (five deep vein thrombosis, two pulmonary embolus (1 death), one myocardial infarct). Late complications were lymphoedema (n = 10), pectoralis major wasting (n = 6), frozen shoulder (n = 7), intercostobrachial neuralgia (n = 4), and a small number of self-limiting wound problems (n = 9). There were two late deaths (myocardial infarcts). Early complications were not related to nodal status, and late complications were related to neither nodal status nor radiotherapy. Significant morbidity is attached to radical surgery for breast cancer. Most complications are minor and self-limiting, but there are a small number of late complications which may affect quality of life. PMID- 1416702 TI - A study of the effect of Picolax on body weight, cardiovascular variables and haemoglobin concentration. AB - This study compared the effect of Picolax when administered for large bowel preparation in combination with preoperative fasting on body weight, haemoglobin concentration, haematocrit, and cardiovascular variables with matched subjects who were fasted before surgery. Picolax resulted in significantly greater weight loss, increases in haemoglobin concentration combined with cardiovascular changes suggesting hypovolaemia in the Picolax group. Intravenous fluid replacement is recommended in patients receiving Picolax. PMID- 1416703 TI - Limb exsanguination. I. The arm: effect of angle of elevation and arterial compression. AB - Limb exsanguination before tourniquet inflation is usually accomplished using mechanical devices although, where their use is contraindicated, exsanguination by elevation alone may be employed. Advice regarding duration of elevation within the literature is a little confusing with recommendations ranging from 20 s to 5 min. Volume changes, during elevation at 45 degrees and 90 degrees, were measured using strain gauge plethysmography in seven male volunteers. In addition, the superimposed effect of brachial arterial compression on elevation at 90 degrees was investigated. To achieve maximal exsanguination it is recommended that the arm should be elevated for 5 min at 90 degrees before tourniquet inflation. Supplementary brachial arterial compression is not recommended as this tends to attenuate changes in volume. PMID- 1416704 TI - Limb exsanguination. II. The leg: effect of angle of elevation. AB - Although limb exsanguination prior to tourniquet inflation is usually accomplished using mechanical devices, elevation alone may still be employed under circumstances where mechanical means are contraindicated. The rather confusing advice within the literature as to duration of elevation, stimulated a study in the arm which revealed the optimal duration of elevation to be 5 min, a period somewhat longer than generally advised. Because the pattern of venous drainage within the leg is slightly different to that of the arm, we undertook a similar study to ascertain if our findings for the arm also held true for the leg. Volume changes in the calves of seven male volunteers during elevation at 45 degrees and 90 degrees were assessed using strain gauge plethysmography. To achieve maximal exsanguination it is recommended that the leg should be elevated at an angle of 45 degrees for 5 min. Higher angles of elevation produce slower and less complete exsanguination. PMID- 1416705 TI - Ionising radiation: are orthopaedic surgeons at risk? AB - Modern orthopaedic trauma practice involves increased exposure of the surgeon to ionising radiation. However, there have been no studies to investigate whether the doses received are within limits for non-classified workers. In this study, whole body, eye and extremity, namely hand, doses were measured in six orthopaedic surgeons during trauma cases requiring the use of X-rays in theatre. None of the subjects approached the recommended maximum dose levels for either the whole body, eyes or hands. This finding is reassuring. In orthopaedics, the limiting dose is that to the hands. This differs from previously studied groups, such as radiologists and cardiologists, in whom the limiting factor is the dose to the lens of the eye. Although current precautions appear to be adequate, safe practice in the future will depend on continuing vigilance and repetition of studies similar to this one as techniques and workloads change. PMID- 1416706 TI - Phytobezoar: an uncommon cause of small bowel obstruction. AB - Phytobezoars are an unusual cause of small bowel obstruction. We report 13 patients presenting with 16 episodes of small bowel obstruction from phytobezoars. Eleven patients had previously undergone surgery for peptic ulceration (eight truncal vagotomy and pyloroplasty). A history of ingestion of persimmon fruit was common and the majority of cases presented in the autumn when this fruit is in season. One phytobezoar causing obstruction at the third part of the duodenum was removed by endoscopic fragmentation, while an episode of jejunal obstruction was precipitated by endoscopic fragmentation of a gastric bezoar. Twelve patients underwent surgery for obstruction on 15 occasions, with milking of the phytobezoar to the caecum performed in ten, enterotomy and removal in four and resection in one patient. Associated gastric phytobezoars were found in two cases and multiple small bowel bezoars in two other cases. These were removed to prevent recurrent obstruction. Phytobezoar should be considered preoperatively as a cause of obstruction in patients with previous ulcer surgery. Wherever possible milking of a phytobezoar to the caecum should be performed. Careful assessment for other phytobezoars should be made. Prevention of phytobezoars is dependent upon dietary counselling of patients by surgeons after gastric resection or vagotomy and drainage for peptic ulcer. PMID- 1416707 TI - Delayed intracerebral haematomas in moderate to severe head injuries in young adults. AB - The incidence of delayed intracerebral haematoma formation in moderate to severely head-injured young adults who do not have signs of cerebral contusions on the initial post-trauma head CT scan has been studied. Thirty patients were reviewed and in 6 (20%) a delayed haematoma was diagnosed on a later CT scan, when signs of cerebral contusions were absent initially. Recurrence of intracranial hypertension within 3 to 4 h proved to be a significant indication for the development of these haematomas, despite the initial but inconsistent good response to osmotic diuretics. The average Glasgow outcome score was 3, including two mortalities. Cerebral perfusion pressure directly correlated with the outcome. PMID- 1416708 TI - A departmental audit of patients with bladder cancer. AB - In keeping with the recent demands of the Department of Health for medical audit in clinical practice, an audit was undertaken of the management of bladder cancer patients in a large department of urology having three consultants with varied approaches of management. This study revealed interesting controversial areas for further scrutiny. For example, the poor prognosis of grade 3 T1 tumours with and without associated carcinoma-in-situ (CIS) and the speed of progression to invasive disease have indicated that a change to a more aggressive approach to the management of these tumours is necessary. High recurrence rates at the site of the original tumour (60%) and the presence of CIS also indicate the need for expert and thorough initial tumour assessment. The delays in diagnosis and treatment lend further support to the need for a 'haematuria clinic' to minimise such delays, which may influence prognosis. To reduce the occurrence of systematic errors in the recording, follow-up and surveillance of patients with bladder cancer, a protocol is suggested for a structured approach to optimise results, particularly in the poor prognostic categories. PMID- 1416709 TI - Intestinal ischaemia in the unconscious intensive care unit patient. AB - This paper highlights the difficulties of diagnosing intestinal ischaemia in unconscious patients on an intensive care unit. We have analysed the clinical details and investigations of eight such patients in whom a preoperative diagnosis of intestinal ischaemia was made on clinical grounds. Intestinal ischaemia was confirmed at laparotomy in only four cases (50%). These patients showed no significant differences in any of the commonly accepted parameters of intestinal ischaemia from the four patients who had a negative laparotomy. In particular, all patients exhibited a metabolic acidosis with fever and a leucocytosis. There was a mean delay of 13.6 h between surgical opinion and laparotomy in the four patients with ischaemia, only one of whom was salvaged. There was no morbidity associated with the laparotomy in this small series. It is suggested that, in the intensive care setting, early laparotomy should be performed immediately the clinical suspicion of intestinal ischaemia arises. PMID- 1416710 TI - Blood loss and transfusion requirements in total joint arthroplasty. AB - We report a prospective trial of 100 consecutive patients undergoing primary total hip or knee arthroplasty in order to assess their blood transfusion requirements amid recent fears of the transmission of viruses, particularly hepatitis C, from donor to recipient. Of the patients, 84% were transfused one or more units of blood in the perioperative period and the mean percentage blood loss per replacement represented 30% or less of their estimated circulating blood volume. We suggest that with preoperative blood volume calculations and haemoglobin concentrations, a more cautious approach to blood transfusion should be employed when other blood volume expanders would suffice. We believe, firstly, that where blood losses of 30% or less of the blood volume occur, blood transfusion is not always required in patients with high haemoglobin concentrations and large blood volumes. Secondly, cross-matching should be undertaken according to the individual patient's estimated needs, rather than to a group as a whole. PMID- 1416711 TI - Acute colonic pseudo-obstruction: a pharmacological approach. AB - Acute colonic pseudo-obstruction is a functional disorder that closely mimics mechanical large bowel obstruction, and in which inadvertent laparotomy carries a high mortality. Eleven such patients were treated by pharmacological manipulation of the autonomic innervation to the colon with guanethidine and neostigmine. Eight responded to treatment with passage of flatus and/or stool within 10 min with complete resolution of symptoms. In three patients the treatment failed. Postural hypotension occurred in only one patient and no other serious side effect was apparent. This pharmacological approach to the management of acute colonic pseudo-obstruction is suggested as an alternative to the other treatment options of colonoscopic decompression or surgery, when conservative management has failed. PMID- 1416712 TI - Emergency treatment of tracheal tear during pharyngolaryngectomy. AB - Longitudinal tracheal tear (of the trachealis muscle), an unusual but acknowledged complication of pharyngolaryngectomy, was encountered during a total pharyngo-oesophagolaryngectomy with gastric replacement. Due to serious ventilatory difficulties a rapid repair was required to obtain an airtight seal to allow continued mechanical ventilation. A reinforced polytetrafluoroethylene (PTFE) vascular graft was used as an intratracheal stent to seal the air leak. This technique proved effective and the tracheal defect had healed by the time the stent was removed 10 days later. PMID- 1416713 TI - Smoke evacuation during surgery. PMID- 1416714 TI - Unsuccessful outpatient counselling to help patients with peripheral vascular disease to stop smoking. PMID- 1416715 TI - Radical axillary dissection in the staging and treatment of breast cancer. PMID- 1416716 TI - Amputations in diabetics. PMID- 1416717 TI - The prognostic value of nucleolar organiser regions in colorectal cancer: a 5 year follow-up study. PMID- 1416718 TI - Non-specific abdominal pain: the resource implications. PMID- 1416719 TI - Carcinoma of the major salivary glands. PMID- 1416720 TI - Care of road traffic accident victims in a district general hospital. PMID- 1416721 TI - Providing the ideal surgical service. PMID- 1416722 TI - The Royal London Hospital Helicopter Emergency Medical Service: first phase 1990. AB - A Helicopter Emergency Medical Service (HEMS) has been introduced to improve trauma care in the Southeast of England. The majority of the workload comes from the area bounded by the M25 ring road. In 1989 a Dauphin 365N helicopter equipped for pre-hospital primary rescue and emergency inter-hospital secondary transfer was certified by the Civil Aviation Authority. The helicopter commenced carrying patients with a paramedic and a doctor on board early in 1990. In September 1990 this service was further improved by the opening of a helipad at the Royal London Hospital and a designated HEMS desk at London Ambulance Service central control. Eighty-four patients were transported in primary rescue missions and 107 as emergency transfers in 1990. PMID- 1416723 TI - Surgical training in developing countries. PMID- 1416724 TI - Pulmonary intravascular macrophages: a review of immune properties and functions. AB - Pulmonary intravascular macrophages (PIMs) are mononuclear cells found apposed to the lung capillary endothelium in a number of mammalian species. Although first described in the 1970s, it was not until the 1980s that they were more completely described. In several species of veterinary interest (bovine, porcine, ovine, and feline), PIMs are very important in blood clearance, which is not the case in mice and rats. Only recently have the immunological activities of PIMs been verified. In this review, we present an overview of PIM research with particular emphasis on the immune functions of this highly reactive macrophage population. PMID- 1416725 TI - Slow release bolus for small ruminants: in vitro release of tetracycline compared with serum concentrations of the antibiotic in sheep. AB - Two formulations of slow release boluses for small ruminants containing tetracycline hydrochloride in a compressed form were investigated in vitro and in vivo in adult sheep. An in vitro dissolution test was used for the preliminary selection of the 2 boluses. It was shown that the non-cumulative kinetics of tetracycline release in vitro were predictive of the tetracycline serum levels in sheep treated orally with the 2 boluses. The maximum concentrations revealed by the in vitro and in vivo curves were obtained at almost the same Tmax and, in vivo, the therapeutic serum levels were maintained for about 5 days. It is concluded that an in vitro approach is of value in predicting the kinetic profiles of a long-acting tetracycline bolus in sheep. PMID- 1416726 TI - Susceptibility of the rabbit to an enteropathogenic strain of Escherichia coli 0103: effect of animals' age. AB - Experimental infections with an enteropathogenic strain of Escherichia coli 0103 were studied in SPF rabbits of different ages. Whatever the age, the weight gains in all animals were reduced more or less significantly. However, mortality differed considerably according to the age. Four to 5-week-old rabbits were most susceptible to the infection, with 80-100% mortality associated with diarrhoea, generally of the hemorrhagic type. Peak mortality was observed between 5-10 days post-inoculation. In general, 21-day-old rabbits died from the second week post inoculation onwards. After the 6th week of age, mortality was rare. Study of the microflora showed that the colonization of the gut by E coli 0103 occurred whatever the age as 10(6)-10(9) bacteria per g of feces of the inoculated strain were recovered. The role of specific receptors has been discussed. PMID- 1416727 TI - Assessment of liver copper status in cattle from plasma copper and plasma copper enzymes. AB - Copper status determined by liver biopsy was also assessed by 3 plasma parameters: total plasma copper (Cu) as well as ceruloplasmin (Cp) and amine oxidase E.C.1.4.3.6. (AO) activities. While 14 out of the 98 cattle, all kept in field conditions, had liver copper levels of less than 20 mg/kg only 5 of these could be distinguished by low plasma Cu and 3 by low Cp activity. In addition, some animals with apparently adequate liver copper had relatively low plasma Cu values, ca 0.5-0.6 mg/l. None of the cattle had decreased AO activity. When all 3 plasma parameters were combined in the form [AO] divided by ([Cp] x [Cu]), detection of the low liver copper was improved in that 9 out of 14 could be distinguished, whereas animals with more than 20 mg/kg DM liver Cu could not. It is suggested that this relationship, tentatively called an index, would merit examination in other situations, since it might provide a better guide to copper status and indicate whether copper repletion therapy was worthwhile. PMID- 1416728 TI - In vitro colonization of porcine trachea by Mycoplasma hyopneumoniae. AB - Porcine tracheae maintained in culture were used in order to study the colonization by Mycoplasma hyopneumoniae. Rings excised from tracheae of newborn piglets were infected with M hyopneumoniae strain BQ 14 and, after different incubation times, were examined by light and electron microscopy. Non-infected tracheal mucosae maintained a normal appearance for several days. Infected tracheal rings showed progressive colonization with concomitant progressive damage to the mucosal surface. Early on during the infection, few mycoplasmas occurred over a ciliated epithelium. As the infection progressed, there was gradual loss of cilia; mycoplasmas tended to form microcolonies and to accumulate over the remaining ciliated cells. Mycoplasmas, first seen at the apex of the cilia, were then seen deeper in the inter-ciliary space; some were even seen in contact with microvilli. In histological investigation, the final stage of the infection was characterized by a marked destruction of the epithelium with exfoliation of the epithelial cells. Infected mucosae showed typical damage caused by M hyopneumoniae, namely reduction of ciliary activity after 5 days, loss of cilia, and sloughing of ciliated cells. Our data indicate that porcine tracheal organ culture can be advantageously used to study colonization by M hyopneumoniae. PMID- 1416729 TI - [The major histocompatibility complex of humans]. PMID- 1416730 TI - [Physical mapping of the major histocompatibility complex of cattle]. PMID- 1416731 TI - [The T-lymphocyte receptor]. PMID- 1416732 TI - Structure and diversity of ruminant T-cell receptors. PMID- 1416733 TI - [Regulation of the immune response by HLA molecules]. PMID- 1416734 TI - [Assembly and intracellular transport of HLA molecule antigen presenters]. PMID- 1416735 TI - [Monoclonal antibodies defining the differentiation cluster of the human leukocyte membrane: use of the characterization of leukocyte subsets]. PMID- 1416736 TI - [General aspects of the early stages of T-lymphocyte activation]. PMID- 1416737 TI - [T-lymphocyte activation: transcriptional and post-transcriptional events]. PMID- 1416738 TI - [Role of the thymic epithelium in the induction of tolerance in birds]. PMID- 1416739 TI - Local and systemic cellular immunity following oral infection of mice with Toxoplasma gondii cysts. PMID- 1416740 TI - [Allorecognition of BoLA class II molecules presented in vitro in liposome membranes]. PMID- 1416741 TI - [The function of cytotoxic T cells]. PMID- 1416742 TI - [Mucous compartments of T-lymphocytes: functions and migration]. PMID- 1416743 TI - The cytotoxic T cell: MHC restriction, strain specificity and role in immunity to Theileria parva infection. PMID- 1416744 TI - [Virus-lymphocyte interactions for the production of alpha-interferon]. PMID- 1416745 TI - [Blood-brain barrier and immunity]. PMID- 1416746 TI - [Human endothelial cells activated by interferon gamma, by interleukin-1 and TNF inhibit the replication of Toxoplasma gondii]. PMID- 1416747 TI - [Suppressor effect of TGF-beta 1 on the immune response in the chicken]. PMID- 1416748 TI - [Has interleukin 2 modified the outcome of metastatic renal cancer?]. PMID- 1416750 TI - [Hepatic resections for metastases]. AB - Between January 1981 and December 1990, 79 liver resections were performed for hepatic metastases in 73 patients. Eight of these patients had a repeat resection (2 patients had their first resection performed before 1981). This figure represented 35% of 228 liver resections performed during this period. Mean age was 56.5 years (23 to 81 years). There were 38 men and 35 women. Fifty-four resections were performed for colorectal metastases and 25 resections for secondaries of other origins. There were 45 major hepatectomies (57%), defined by the resection of at least 3 Couinaud segments, and 34 minor resections (less than three segments). In 12 patients, liver resection was associated with excision of the primary tumor. Complications were observed in 25 patients (32%), pulmonary complications being the most frequent. Five re-explorations were necessary: 3 for postoperative bleeding, one for an abdominal abscess and one for intestinal obstruction. Mean postoperative stay was 18 days. There was no mortality for the first liver resections in 71 patients. One death was encountered among the second resections in 8 patients, with a global mortality of 1.3%. Follow-up was obtained for all patients but one (lost to follow-up at 5 years). Actuarial survival for the 50 patients operated on for colorectal secondaries was 98% at 6 months, 83% at 1 year, 46% at 2 years, 24% at 3 years and 15% at 5 years. In non-colorectal secondaries, the survival depended on the nature of the primary tumor but was very different from one patient to another.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416749 TI - [Perioperative transfusion strategy]. AB - Tactics in blood transfusion have evolved considerably during the last ten years. Awareness of infectious risks and economic considerations have lead legislators to draw the guidelines for a safer transfusion. Their aim is to promote a better transfusion in smaller quantities at a lower risk. The goal of perioperative blood replacement is to maintain hemoglobin, blood volume and coagulation factors at an adequate level. This can be carried out by either homologous or autologous transfusion. Fresh frozen plasma transfusion is only required in severe bleeding where coagulation factors are depleted. The plasma substitutes must be used according to their intrinsic properties and their cost. The choice of an autologous technique depends on the type of surgical procedure, the expected blood loss and the economic resources available. Autologous blood transfusion may be optimized by the association of various techniques. This transfusion strategy must be elaborated by all the medical protagonists implicated in transfusion procedures. PMID- 1416752 TI - [Endoscopy of the small intestine in 1991: is it the end of the tunnel?]. AB - Small bowel enteroscopy in 1991 is now feasible in two clinical situations: in the case of malabsorption or diffuse intestinal disease, it is easier to visualise the small bowel with the "push enteroscopy methods". The most proximal and distal ends of the small intestine can be viewed through standard instruments or better with videocoloscope beyond the ligament of Treitz. The ileocecal valve can be intubated after total colonoscopy for the evaluation of Crohn's disease, tuberculosis and small bowel lymphoma. In the case of occult gastrointestinal hemorrhage small bowel enteroscopy now permits visualization of large amounts of small intestinal. When the gastrointestinal bleeding is severe, we recommend intraoperative enteroscopy. When the bleeding is not severe and chronic, it is possible to perform a non surgical total small bowel enteroscopy with an enteroscope or videoenteroscopoe. Prototypes are under development. The procedure is safe an can be performed on an outpatient basis. The limitations of the procedure are the impossibility of intervention and inability to inspect the total mucosal surface. It is not a "first line" or "second line" investigation in these situations. It should be considered after previous investigations have been negative. Push enteroscopy should be performed by general endoscopists, non surgical and total enteroscopy should be reserved, for instance for skills and motivated team endoscopists. PMID- 1416751 TI - [Results of portacaval shunt after failure of sclerotherapy in patients with cirrhosis]. AB - Therapy of variceal bleeding is currently based on endoscopic sclerotherapy. However, the treatment of bleeding recurrences after sclerotherapy has not yet been established, but consists of the choice between continuation of sclerotherapy or a surgical procedure. We report herein the results of portocaval shunt performed in 26 cirrhotic patients among the 175 cirrhotic patients (15%) admitted between 1985 and 1990 to our Intensive Care Unit for variceal bleeding. These 26 patients were operated because of failure of sclerotherapy as defined by haemostasis failure (n = 1), the persistence of unchanged oesophageal varices after six sessions of sclerotherapy (n = 1), and the occurrence of at least one severe episode of rebleeding (n = 24). Emergency and elective portocaval shunts were performed in 12 and 14 cases respectively. The time delay between admission and surgical procedure was equal to 21 +/- 8 hours and 12 +/- 4 days in the two groups respectively. The operative mortality (30 days) was equal to 23% and was observed in emergency shunts only. Actuarial survival rates were significantly different between the two groups (p < 0.01). Predictive factors of mortality as assessed by univariate analysis were the emergency nature of the procedure, serum aminotransferases and urea levels at the time of the index bleeding, and the number of bleeding episodes related to portal hypertension before the index bleeding. The prognosis at one year was not influenced by the number of bleeding recurrences between the index bleeding and the bleeding episode justifying the shunt.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416753 TI - [Cholecystectomy by celioscopy. Experience in two Upper Normandy hospital units. Apropos of 178 procedures]. AB - Laparoscopic cholecystectomy (LC) emerges as an effective alternative to classical cholecystectomy, but its safety, benefits and indications still need to be clarified. From September 1989 to March 1991, 178 LC were performed by 8 surgeons in 2 hospitals, on 142 women and 36 men with a mean age of 48.2 years. The gall bladder wall was thin in 160 cases and thick in 18 cases (with 6 cases acute cholecystitis). We observed no deaths, 147 simple procedures with a hospital stay and drug requirement lower than with the usual cholecystectomy via laparotomy. But in 21 cases, the procedure needed a laparotomy, and in 10 cases complications occurred, requiring laparotomy in 6 cases. Our results suggest: a) LC is an improvement in the treatment of uncomplicated gallstones; b) a trained surgeon and extreme caution are required in complicated cholelithiasis; c) classical cholecystectomy is still useful in many circumstances. PMID- 1416754 TI - [Appendectomies by celioscopy. Results in 78 patients]. AB - The recent development of laparoscopic surgery has included the treatment of acute appendicitis. We report our results after three years' experience of this type of surgery. We have operated on 78 patients (54 men, 44 women) mean age 28.9 years, suspected of varying degrees of acute appendicitis. The operation was completely carried out by laparoscopy on 71 occasions, including treatment of an abscess in 4 cases and peritonitis in 4 cases (3 of which were sub-mesocolic and one was generalised). The laparoscopy was transformed into laparotomy in 7 cases, 4 of which were due to difficulties of appendix dissection. Mortality was zero. Four complications occurred: 2 minute infections of the trocar hole, one more severe parietal infection which was a cause of readmission and antibiotic treatment, one "syndrome of the fifth day". In conclusion, laparoscopic appendicectomy appears to be quite feasible in the majority of cases, particularly when the appendix is ectopic, with marked abdominal thickening and peritoneal reaction. The postoperative course is uneventful. The laparoscopic technique is very comfortable for the patient during the postoperative period. This technique is becoming increasingly feasible with the operator's experience, and this appears to us to constitute good training for any form of laparoscopic surgery. PMID- 1416755 TI - [Gastric metastases. Apropos of 17 cases]. AB - Seventeen cases of gastric metastases are reported; some of them appeared after a long latency period. Two cancers prevail from an aetiological standpoint: melanoma (7 cases) and breast cancer (4 cases). Endoscopic appearance is often typical in melanoma, but suggests a primary carcinoma or radiation-induced lesions in breast cancer. Surgery is reserved to located lesions, but seems to have no incidence on prognosis. Overall mean survival is 11 months with a range of 3 months to 5 years. PMID- 1416756 TI - [Leiomyosarcomas of the rectum. Amputation of the rectum or local resection?]. AB - Two cases of high grade leiomyosarcoma of the rectum treated by local excision are reported. The first patient presented a local recurrence associated with liver and pulmonary metastases and eventually died, respectively 11 and 22 months after resection. The second patient's tumor recurred 3 months after excision and was treated with pelvic exenteration and CYVADIC regimen as chemotherapy and died 3 years later from local recurrence. A review of the literature indicates that local surgical excision in comparison to a more radical surgical approach, such as abdominoperineal resection, is as effective in improving survival. Lesions less than 2.5 cm in diameter, confined to the bowel can be treated by local surgical excision. To date no adjuvant therapy is effective in terms of survival or local control. PMID- 1416757 TI - [Implantable insulin pump: surgical implantation under local anesthesia. (Technical note apropos of 35 cases)]. AB - The authors report 35 cases of implantation of a programmable implantable insulin pump, under local anesthesia. This technique allows creation of an subcutaneous pocket and introduction of an intraperitoneal catheter for insulin delivery. The morbidity is mainly due to the catheter which becomes thrombosed by a fibrotic pannus at its tip. We observed only one case of mechanical dysfunction of the pump. Subcutaneous migration is secondary to reoperation without new fixation. With a mean follow-up of 7 months, 75% of the patients are doing well. PMID- 1416758 TI - ["Cholethorax" revealing injury to the common bile duct after celioscopic cholecystectomy]. AB - The case-report describes the unusual formation of a bilious pleural effusion or "cholethorax" revealing a common bile duct injury secondary to laparoscopic cholecystectomy. Pleural drainage led to a diagnostic ERCP. Subsequently a Roux en Y hepatico-jejunostomy allowed a satisfactory outcome. PMID- 1416759 TI - [Surgical treatment of toxic megacolon complicating pseudomembranous colitis. Apropos of a case, review of the literature]. AB - Toxic megacolon complicating pseudomembranous colitis has been rarely observed. Only 36 cases have been previously reported. We present herein a new case report in which pseudomembranous colitis was secondary to prophylactic antibiotherapy with pefloxacin for hip prosthesis. Despite specific oral treatment (against Clostridium difficile) by vancomycin, toxic megacolon required urgent subtotal colectomy with ileostomy and sigmoidostomy. Postoperative course was uneventful. Analysis of the reported cases demonstrates the high overall mortality of the series (32%); the procedure of choice seems to be subtotal colectomy, which removes the septic focus, with a 12% operative mortality rate. PMID- 1416760 TI - [Training of surgeons in the Netherlands]. PMID- 1416761 TI - [Anterior seromyotomy and posterior vagotomy in the treatment of perforated duodenal ulcer]. PMID- 1416762 TI - [Regulation of arteriolar tonus and EDRF]. AB - The physiological significance of the release of NO by endothelial cells was discussed according to the effects of inhibitors of NO formation and to the observations of Mellander et al. on the reactivity of resistance vessels in cat skeletal muscle. Whole results indicate that NO continually takes patent arteries and decreases systemic resistances. However, NO has minimal effects on the arteriolar side of the vascular tree. PMID- 1416763 TI - Indication for surgery of asymptomatic carotid lesions. AB - The incidence of cerebrovascular diseases with transient or persistent neurologic dysfunction has increased significantly. Although patients with symptomatic carotid artery stenosis clearly benefit from operative therapy, the indication to prophylactic surgery of asymptomatic carotid lesions however is still controversial. Based on data from a recently completed prospective randomized study and on analysis of the literature the indication and results of surgical treatment of asymptomatic stenoses of the carotid arteries are discussed. From 1970 to 1990 a total of 744 uni-or bilateral reconstructions of the internal carotid artery were performed in 631 patients. The perioperative morbidity (permanent neurologic deficiency) and mortality was 1.1% (n = 8) resp. 0.8% (n = 6). During the follow up period up to 18 years another 9 patients suffered from stroke (1.2%). The annual stroke incidence amounted to 0.2%. An important prerequisite for surgery is the so called critical internal carotid artery stenosis, implying reduced cerebral vasomotor reactivity or high embolic risk of an ulcerative plaque. Proper selection of patients (exclusion of multiple concomitant diseases) and an experienced team of vascular surgeons with operative morbidity and mortality below 1-2% validates surgical treatment of asymptomatic carotid artery stenoses. PMID- 1416764 TI - [Measurement of cardiac output by invasive methods: methods and variability]. AB - Invasive techniques for the measurement of cardiac output include the Fick method, the marker dilution method and radiological ventriculography. The principles, methods and accuracy of these techniques are described. The reference method remains that of Fick, despite its being less widely used now because of its complicated nature and its technical limitations (need for strict baseline conditions, precision of sampling). The thermodilution method is often performed. It is easy and provides reliable results, except in conditions of low cardiac output or when there is severe tricuspid insufficiency. Radiological ventriculography is used less for the measurement of cardiac output, since it is heavily dependent upon heart rate and theoretical geometrical models. It remains valuable for the quantification of mitral and aortic regurgitation. PMID- 1416765 TI - [Evaluation of cardiac output by Doppler echocardiography. Basic principles and practice]. AB - The measurement of cardiac output by the Doppler-echocardiography method is of considerable interest since, in contrast to other available techniques, it offers the possibility of the measurement of output at each valve orifice, thus providing a quantitative approach to valve regurgitation. The 4 basic data items required are: the surface area of the valve orifice, trans-valvular Doppler velocity spectrum, duration of ejection and of filling, and heart rate. A large number of studies have analysed the various investigation techniques and have shown their excellent correlation with reference invasive methods. In the light of experience acquired in our Echocardiography Laboratory, we recommend, in accordance with data from the literature, the exclusive use of pulsed Doppler and measurement of valve orifices by two-dimensional imaging at the point of insertion of the aortic and sigmoid cusps as well as at the mitral ring. A simplified method for the measurement of mitral surface area on the basis of TM records is suggested. PMID- 1416766 TI - [Evaluation of cardiac output by Doppler echocardiography. Correlation of aortic, pulmonary and mitral ring flow rates. Study of 103 subjects free of valve leak]. AB - Measurement by Doppler-echocardiography of blood flow rates has the advantage over techniques for the measurement of cardiac output of determining the latter for each valve orifice, and of opening up an approach to the quantification of aortic and mitral regurgitation. This prospective study involving 103 subjects free of any valve leak showed the absence of an significant difference between aortic, pulmonary and mitral ring flow rates in a given individual. Correlations between results obtained at the three measurement sites were: r = 0.92 between aorta and pulmonary artery, r = 0.90 between aorta and mitral ring and r = 0.90 between pulmonary artery and mitral ring. These results support the validation of this technique and would justify its use in the evaluation, quantification and monitoring of mitral and aortic valve leaks. PMID- 1416767 TI - [Measurement of mitral flow at the extremity of the valves. Validation of a simplified method based on 101 cases]. AB - The measurement of cardiac output at the extremity of the mitral cusps, by Doppler-echocardiography, is of fundamental value, in particular for the evaluation of valve regurgitation. However, it comes up against a theoretical difficulty resulting from constant variation in the surface area of this orifice during diastole. After reviewing the main measurement methods available in the literature, a simplified method based upon the diameter of the ring and calculation of a mean diastolic intercusp distance by TM is suggested. Evaluation of this technique in 101 patients free of valve of leak showed its feasibility to be close to 100% and the correlation with aortic (r = 0.90), pulmonary (r = 0.91) and mitral ring (r = 0.88) outputs was entirely satisfactory. Our method would thus seem to be a good compromise between digitalised integration methods for the measurement of mitral surface area--optimal but complex--and the aim of simplification compatible with routine clinical use. PMID- 1416768 TI - [Measurement of cardiac output by Doppler echocardiography at the 4 cardiac valves]. AB - Many observers remain sceptical with regards to the utilization of Doppler echocardiographic measurements of intracardiac outputs for the quantification of shunts and regurgitations. In this context, we evaluated the feasibility and validity of measuring output at the level of the four cardiac valves in a population of 35 normal subjects (24 M, 12 F) aged from 23 to 37 years (mean +/- SD = 28 +/- 4). Measurement of stroke volume and output using predetermined criteria was possible in the aortic position in 35 (100%) subjects, in the mitral position in 34 (97%), in the pulmonary position in 20 (57%) and in the tricuspid position in 10 (29%). In 14 subjects (40%), measurement was possible at 2 sites, in 14 (40%) at 3 sites and in 7 (20%) at 4 sites. Inability to measure output was most often due to poor visualization of valvular annulus. There are excellent correlations between aortic stroke volume on the one hand and the mitral (r = 0.97, SEE = 3.41 cc), pulmonary (r = 0.97, SEE = 3.69 cc) and tricuspid (r = 0.96, SEE = 2.77 cc) stroke volumes respectively on the other. These results suggest that reliable measurements of output are feasible in a majority of cases in the aortic and mitral positions but to a much more limited extent in the pulmonary and tricuspid positions; given the small SEE's, they should be useful to quantitate shunts and regurgitations, when feasible. PMID- 1416769 TI - [Determination of aortic and pulmonary flow by Doppler ultrasonography]. AB - Numerous studies have demonstrated the reliability of ultrasound Doppler in measuring aortic flow. It is generally agreed that aortic surface area and flow rate should be measured at the arch. In contrast, determination of the pulmonary flow by ultrasound Doppler, validated in children and infants, is difficult in adults due to problems encountered in measuring the diameter of the pulmonary arch. PMID- 1416770 TI - [Quantification by transthoracic Doppler of tricuspid valve insufficiencies]. AB - Various methods are available today for the quantification of regurgitation by transthoracic Doppler. The present review deals with their respective usefulness in tricuspid insufficiency (TI). Despite their contribution in the domain of mitral and aortic insufficiency, precise quantification methods remain of very limited value regarding the tricuspid orifice, and this because of practical difficulties of application. Evaluations of the severity of TI is based, essentially, on a semiquantitative approach. Cartography of the regurgitation stream, by colour Doppler, is the chief method, despite its limitations which are clearly emphasised by the effects of the contrast test. The discovery, by pulsed Doppler, of laminar systolic flow is a sign of capital importance. It is indicative of massive TI and of particular anatomical and hemodynamic conditions, but it is uncommon. Systolic reversal of flow in the inferior vena cava is a good sign of severity but lacks specificity. In contrast, measurement of maximum velocities of TI, while essential for the evaluation of pulmonary pressures, is of no value in terms of the quantification of regurgitation. Transthoracic Doppler data must be taken together with those of transthoracic echocardiography, the esophageal approach offering nothing special, being essentially useful in lesion evaluation. The quantification of TI, by transthoracic Doppler, has derived only very little benefit from the current orientation of Doppler methods. PMID- 1416771 TI - [Measurement by Doppler echocardiography of the ratio of pulmonary/systemic flow rates in atrial septal defects. Apropos of 15 cases]. AB - Fifteen patients with an ostium secundum type atrial septal defect, aged between 5 and 68 (mean = 31) underwent Doppler-echocardiographic evaluation of the ratio of pulmonary and systemic flow rates. Systemic flow was evaluated at the aortic orifice, as well as at the mitral ring and at the extremities of the mitral cusps, based upon the measurement of valve diameters by 2D or TM echocardiography, pulsed Doppler velocity curve and hear rate. Pulmonary flow was measured by the same technique at the site of insertion of the pulmonary cusps. The values obtained were compared with cardiac catheterisation findings, the reference method being an oxymetric measurement of the shunt ratio. Feasibility of the Doppler investigation was 100 per cent. Correlation between the two techniques was r = 0.85 when the Doppler measurement was at the aorta, r = 0.81 for the mitral ring and r = 0.71 at the extremity of the mitral cusps. Doppler echocardiography thus appears to be a reliable and reproducible method for the evaluation of left-right shunts, confirming data from the literature. PMID- 1416773 TI - [Transesophageal echocardiography in infectious endocarditis]. AB - During the past 20 years, TTE has acquired a role of choice in the positive diagnosis as well as in the prognostic evaluation of endocarditis. However, it is a non-histobacteriological technique and is also operator-dependent. If often enables the detection of high risk patients: large vegetations, severe valve damage with major leaks, threatened complications: abscess, fistula, sometimes leading to referral of the patient for emergency surgery when required by hemodynamic conditions (often without recourse to catheterisation) or when infection is uncontrolled despite proper medical treatment. Embolism is the chief cause of morbidity and mortality in IE. In this context, the size of vegetations appears to be a risk factor. TEE enables refinement, precision and completion of TTE findings. It should be requested in the following circumstances: 1) strong clinical suspicion of IE but TTE negative, 2) monitoring of severe forms due to virulent organisms, 3) whenever there is suspicion of IE affecting a valve replacement. PMID- 1416772 TI - [Doppler echocardiography and double chamber pacing]. AB - Doppler-echocardiography is playing an increasing role in cardiac pacing: 1) Before implantation, to determine any cardiac disease possibly accompanying the conduction disturbance, and the quality of atrial function in order to identify the appropriate indications for the type of pacing which will restore normal AV synchronism. Alongside morphometric data (size of atria, etc.), this analysis is based above all on the evaluation of LV filling flows and ejection, if necessary during provisional pacing in DRV mode. It is important to be aware of and prevent certain problems: 1st degree AV block with very long PR, high degree interatrial conduction disturbances, etc. 2) To evaluate the possible benefits of pacing in certain new indications, e.g. obstructive hypertrophic cardiomyopathy (measurement of intra-LV gradient in sinus rhythm and with DRV pacing with total ventricular capture). 3) After implantation, to optimise the programming of double-chamber pacemakers and in particular AV intervals (base-line AV interval with paced atrial cycle, AV interval with detected atrial cycle, hysteresis of AV interval corresponding to the difference between the two previous values, slope of automatic variation in AV interval during exercise, etc.). Individual programming of these parameters based upon analysis of transmitral and ejection flow rates, at rest and, if necessary, during exercise, enables the optimisation of cardiac function (which is above all useful in the presence of concomitant organic heart disease) while at the same time improving the electrophysiological behaviour of the pacemaker at high frequencies. PMID- 1416774 TI - Annals editorial review process--improving the quality of publication. PMID- 1416775 TI - An epidemiological survey of respiratory morbidity among granite quarry workers in Singapore: radiological abnormalities. AB - This report presents baseline findings from the first of a series of epidemiological studies to evaluate inter alia the effects of control measures introduced in 1972-79 to reduce dust exposure in all quarries in Singapore. The prevalence of radiological abnormalities among 219 currently employed quarry workers were estimated according to a number of parameters of dust exposure. Large-sized chest x-ray films were read, independently and in random order, by a panel of three experienced readers, who were "blinded" to the personal particulars and exposure of the subjects, using standard chest x-ray films to record opacities according to the International Standard Classification of Radiographs of Pneumoconioses. Silicosis as defined by radiological small opacities (both rounded and irregular) of profusion 1/1 or greater as read by at least two readers were noted in 11 subjects. The prevalence of silicosis was 12.5% in highly exposed drilling and crushing workers, and 0.8% in maintenance and transportation workers with low level exposure to granite dust. Among those who were first exposed to granite dust after 1979, no cases of silicosis were noted in any quarry worker. It is concluded that reduction in dust exposure since 1979 has so far been successful in producing nil or negligible risks of silicosis among active quarry workers over ten years, but further follow-up studies are needed. PMID- 1416776 TI - An epidemiological survey of respiratory morbidity among granite quarry workers in Singapore: chronic bronchitis and lung function impairment. AB - Respiratory symptoms of chronic bronchitis and measurements of lung function were studied in an epidemiological survey of the total population of workers currently employed in granite quarries in Singapore. There were 85 rock drilling and crushing workers with current exposure in high levels of silica dust. Their respiratory parameters were studied with reference to an internal comparison group of 154 quarry maintenance and transport workers with low dust exposure, and an external comparison group of 148 Telecoms postal delivery workers with no granite dust exposure. The highly exposed workers showed greater prevalences of chronic cough and phlegm, a mean reduction of 5% in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). The increased respiratory morbidity were independent of other factors such as age and smoking. Similar results were also noted after excluding those with silicosis (defined radiologically as profusion greater than 1/1 as read by at least two of three readers). This study strongly indicates a demonstrable risk of "occupational" bronchitis (mucus hypersecretion) and obstructive and restrictive lung function impairment, apart from the "classical" risk of silicosis. Measures taken to protect the health of workers exposed to silica dust should also be based on considerations taken to protect against the risk of these respiratory disorders as well. PMID- 1416777 TI - Xq28: epidemiology and sex-linkage between red-green colour blindness and G6PD deficiency. AB - Xq28 is the genetic locus of two closely associated conditions of red-green colour blindness and G6PD deficiency. Epidemiologically, both rank among the more frequent sex-linked clinical problems that affect military servicemen in Singapore. This retrospective study is based on the findings of 35714 subjects screened at the Medical Classification Centre--Central Manpower Base (MCC--CMPB) over an eighteen-month period using pseudoisochromatic and fluorescent techniques as well as anomaloscopic and spectrometric methods. The overall prevalence rates of red-green colour blindness, G6PD deficiency and association were determined to be 4.8%, 2.2% and 0.1% respectively. Malays showed the highest prevalence rates among the major races. Statistically significant difference was found with regards to the prevalence rates of G6PD deficiency and its association with red green colour blindness. Review of literature yielded comparable results with a few local studies of good sample size done over the past twenty years. Sex linkage analysis was hindered by the lack of pedigree studies. PMID- 1416778 TI - A prevalence study of dysmenorrhoea in female residents aged 15-54 years in Clementi Town, Singapore. AB - A community-based questionnaire survey to study the prevalence of dysmenorrhoea, its associated risk factors and impact on daily living was carried out on a random sample of 415 female persons aged 15 to 54 residing in Housing Development Board flats in Clementi Town. The overall prevalence of dysmenorrhoea, defined as one or more episodes of menstrual cramp or pain in the previous year, not due to a diagnosed gynaecological disease, was 51.3%. The condition was less prevalent and less severe in older women and in women with later menarche. It was also less prevalent in women who were parous, with the greatest number of parous women reporting improvement in severity after the first child. Among those with dysmenorrhoea, about 52% of students, 42% of working women, and 30% of housewives reported that their ability to perform work was affected. About 6% of all women consulted a doctor for their problem, and 10% of all employed women reported having been sick-absent because of dysmenorrhoea. PMID- 1416779 TI - Cervical cancer: trends in incidence and mortality in Singapore 1968 to 1987. AB - Analysis of data collected by the population-based Singapore Cancer Registry reveals that the age-standardised incidence of cervical cancer has decreased from 18.2 per 100,000 females in 1968-72 to 16.2 per 100,000 in 1983-87, and its ranking among the most common female cancers has fallen from second to fourth place behind cancers of the breast, colon/rectum and lung. Mortality from the disease has also shown a corresponding fall from 7.3 per 100,000 to 5.5 per 100,000 women over the same period. Cervical cancer incidence rates are in general highest among Indian women, intermediate in Chinese and lowest in Malays. Age-specific incidence curves over time show a marked fall in rates in women over 50 years of age, whereas younger women (35-44 years old) show a small increase. A similar increase in rates has been observed in various other countries. Internationally, Singapore's incidence rate falls between the highs of South America and parts of Asia, and the lower rates of North America and Europe. The decrease in rates is comparable with the overall global trend, but falls short of that achieved by countries with systematic cytological screening programmes. PMID- 1416780 TI - Prevalence of protein calorie malnutrition in general surgical patients. AB - The prevalence of protein calorie malnutrition (PCM) based on ten nutritional parameters was studied in 307 patients undergoing major elective surgical operations. These parameters included anthropometric measurements (weight/height, triceps skin fold thickness, arm muscle circumference) and biochemical (serum total proteins, albumin, transferrin, prealbumin, retinol binding protein) and immunological tests (total lymphocyte count and delayed hypersensitivity test). Using these criteria, the prevalence of PCM was high. Eighty-six percent of patients had at least one abnormal parameter. The prevalence of PCM as judged by weight/height and arm muscle circumference was 49% and 62% respectively. The incidence was higher in cancer than non cancer patients (63% vs 43%). Although serum albumin and total protein levels were normal in 93.5% of patients, acute serum protein markers such as transferrin, prealbumin and retinol binding protein were low in 20-30%. Lymphopenia of 1500 cells/cu mm or less was found in 18% and abnormal delayed hypersensitivity test in 60%. We found that only weight/height, serum protein, transferrin and lymphopenia had predictive values in postoperative morbidity and mortality. By identifying PCM patients early, adequate nutritional support can be given in order to reduce the risk of major surgical complications. PMID- 1416781 TI - Treatment of spontaneous uncomplicated pneumothorax with aspiration. AB - Between December 1989 and December 1990, nine patients with significant, uncomplicated, spontaneous pneumothoraces were treated by simple aspiration in the Medical Department, Alexandra Hospital. Only one had a residual 30% pneumothorax that required further aspiration with good results. The majority of the patients stayed three days in hospital. These nine patients were reviewed at various periods between four weeks to twelve months with no recurrence of pneumothoraces. The discomfort and inconvenience of an intercostal tube insertion was avoided. Risk of damage to the lung was minimal. No scar was left behind. Total cost of the procedure and hospitalisation was much less compared with intercostal intubation. PMID- 1416782 TI - Acute deep vein thrombosis in hospital practice. AB - A recent cross sectional study on symptomatic acute deep vein thrombosis at the National University Hospital (NUH) in Singapore found a frequency rate of 0.79 per 1000 patient admissions. A total of 39 patients were accrued over 18 months, 36 with deep vein thrombosis alone and three complicated by pulmonary embolism. No sex or ethnic predilection was observed in this cohort of hospitalised patients. Twenty-eight (71.8%) patients were 40 years or older. Majority (89.7%) of patients had at least two predisposing factors. While prolonged bedrest and operative procedures featured equally frequently in patients above and below 40 years, neoplasms were predominantly associated with the former and protein C or S deficiency primarily with the latter. The exhaustive laboratory confirmation of an inherent thrombotic tendency is recommended only for patients below 40 years of age. PMID- 1416783 TI - Clinical study of magnetic stimulation of peripheral nerves. AB - Magnetic stimulation of the peripheral nerves is a recently developed technique and has exciting prospects in clinical neurophysiology. An experiment was performed comparing the conventional electric stimulation with magnetic stimulation of the median nerve of a normal population. Magnetic stimulation produced comparable results as far as latency, amplitudes and configuration of action potentials in most patients. The technique of magnetic stimulation is discussed. Its shortcomings are in locating the magnetic coil's point of stimulation on the nerve and difficulty in achieving supramaximal stimulation. Its great advantage is that it is painless and that deep nerves can be reached. PMID- 1416784 TI - Infection in continuous ambulatory peritoneal dialysis (CAPD): aetiology, complications and risk factors. AB - Continuous ambulatory peritoneal dialysis (CAPD) was started in the Singapore General Hospital in 1980. Peritonitis and exit site infections have been the major cause of morbidity and catheter loss in CAPD. In 1990, 130 patients were on CAPD and the peritonitis rate was one episode in 20.4 patient months. Gram positive organisms accounted for 54% of the infections of which Staphylococcus epidermidis was the commonest (24%). Catheter removal was required in 14% of the cases and 9% of the patients discontinued CAPD as a result of peritonitis. The exit site infection rate was one episode in 27.5 patient months and the commonest organism was Staphylococcus aureus (54%). Twenty-three (47%) of the cases of exit site infection required catheter removal and 83% of the cases were the result of S. aureus infections. Patients with preexisting exit site infections experienced more episodes of peritonitis. Patients above the age of 50 years experienced more episodes of peritonitis and exit site infection. Sex, diabetes and the duration on CAPD did not influence the frequency of infections. Patients using the UV Germicidal Exchange Device had fewer episodes of peritonitis than those using the conventional spike system. PMID- 1416785 TI - Community acquired urinary tract infections in Singapore: a microbiological study. AB - We studied 214 patients with culture proven community acquired infections. A total of 219 organisms were isolated, of which 68.2% were Escherichia coli, 10.1% Klebsiella sp and 5.5% Proteus mirabilis. Gram positive cocci accounted for 10.5% of organisms isolated. The majority of organisms isolated were sensitive to nalidixic acid (81.1%), nitrofurantoin (80.7%), cephalexin (74.7%) and trimethoprim-sulphamethoxazole (65.0%). Resistance to ampicillin was common (49.8%), as such the use of ampicillin in community acquired urinary tract infections will result in a high failure rate. PMID- 1416786 TI - The impact of HLA match transfusions and presensitization on renal transplantation in the cyclosporine era. AB - The successful engraftment of a renal transplant is dependent on multiple factors, immunological factors being of major importance. Specifically, histocompatibility, lymphocytotoxic antibodies and pretransplant blood transfusions have been shown to play a major role in determining graft outcome in renal transplant recipients receiving Azathioprine-Prednisolone immunosuppression. The impact of the immunosuppressive drug, Cyclosporine on graft outcome in relation to established risk factors were examined among 116 cadaveric and 34 living related renal allograft recipients from our center. Histoincompatibility and pretransplant blood transfusions did not significantly affect graft survival among cadaveric transplant recipients. Similarly, graft survival was not significantly different between two haplotype-matched and less well-matched living-related graft recipients (75% versus 96.5% respectively). On the other hand, lymphocytotoxic antibodies remained a major risk factor for immunologically mediated graft loss among cadaveric graft recipients (48.0% versus 92.2% four year graft survival among those with and without antibodies respectively). These results suggest that Cyclosporine has abrogated some immunological risk factors in renal transplantation. PMID- 1416787 TI - Management of severe chronic radiation cystitis. AB - Chronic radiation cystitis complicating pelvic irradiation can occasionally result in massive bleeding difficult to control with conventional means. Between 1986 and 1989, we managed 42 cases of chronic radiation cystitis of which nine (21%) were of this severe type based on the necessity for repeated cystodiathermy, massive transfusions and open surgical intervention. We found early cystodiathermy and alum bladder irrigation beneficial in early cases, but six (67%) patients required emergency bilateral percutaneous nephrostomies for proximal urinary diversions to help stop the bleeding. Despite aggressive treatment, two patients (22%) died during their admissions and two others (22%) died shortly after discharge. Three patients eventually required elective ileal conduit diversion for their contracted defunctioned bladder. Thus this group of patients suffered relatively high morbidity and mortality for an essentially benign condition. Increased physician awareness and timely percutaneous nephrostomies may improve results. PMID- 1416788 TI - Exercise training in patients after heart transplantation. AB - The post-cardiac transplantation patient is frequently debilitated as a result of "end-stage" heart disease and typically demonstrates muscle wasting, with a reduced work capacity, maximum heart rate and peak oxygen uptake. At submaximal effort, perceived exertion and ventilation are higher, and the absolute ventilatory threshold lower, than in normals. A number of published studies have now shown that an exercise rehabilitation programme can induce a good training effect, although possibly not complete restoration of physiological function. The prescription of exercise must take into account the denervated heart's peculiar response to effort, and rely more on perceived exertion and metabolic measurements for defining intensity of training rather than target training heart rates. Changes in mood and personality have also been noted in these patients, and while these may improve spontaneously with the passage of time, there is some evidence that a rehabilitation programme can help in this regard. PMID- 1416789 TI - Calcifying epithelioma of Malherbe--a case report of a large preauricular tumour. AB - Calcifying epithelioma of Malherbe (pilomatrixoma) is a relatively uncommon benign skin tumour of hair follicle origin. It usually presents in the face and upper extremities of young adults as an asymptomatic subcutaneous or dermal tumour. Treatment is surgical excision. This paper presents a case of a large tumour in the preauricular region with difficulty in diagnosis preoperatively and required a superficial parotidectomy to clear the tumour from the facial nerve. PMID- 1416790 TI - Migrating foreign bodies in the upper digestive tract. AB - Migrating foreign bodies in the aerodigestive tract are not so uncommon. Two cases of penetrating and migrating extraluminal foreign bodies in the upper aerodigestive tract are presented. Both patients had ingested fish bones. Fish bones are the commonest of bones to be ingested. Sharp and pointed fish bones are more likely to penetrate extraluminally. A high index of suspicion is necessary to institute early treatment. A CAT scan is invaluable in locating the foreign body especially with regards to surgical landmarks at exploration. Early surgical intervention avoids life-threatening complications. PMID- 1416791 TI - Oculopharyngeal muscular dystrophy: a case report and a review of literature. AB - Most muscular dystrophies manifest as peripheral muscular weakness commencing at various age, however, oculopharyngeal muscular dystrophy (OPMD) is a rare hereditary disorder presenting in middle age with progressive dysphagia and bilateral blepharoptosis rather than peripheral muscular weakness. In the medical literature, OPMD has been well described in Canadians of French descent. So far, there is no publication of OPMD in the Malaysia-Singapore medical literature. This article documents this condition in a Chinese patient. A review of the literature is presented and the management of OPMD is discussed. PMID- 1416792 TI - Severe myelodysplasia with monosomies 5 and 7 presenting with rapidly fatal Sweet's syndrome. AB - A 57 year-old Chinese man with anaemia and thrombocytopenia due to monosomies 5 and 7-associated myelodysplasia developed progressive Sweet's syndrome. Recurrent episodes of cutaneous manifestations responded dramatically to corticosteroid therapy. However, progressive pulmonary infiltrates unresponsive to antimicrobial therapy resulted in respiratory failure and death. PMID- 1416793 TI - Fixed drug eruptions due to co-trimoxazole. AB - Co-trimoxazole is a less common cause of fixed drug eruption (FDE). The offending drug is usually sulfamethoxazole but reactions to trimethoprim have been reported. Fixed drug eruption is uncommon in children compared to adults as the drugs most commonly responsible are seldom or never used in children. We report four patients with FDE to co-trimoxazole, three of whom were children. All were given the offending drug for upper respiratory tract infections. Each of the patients had several episodes of FDE before the diagnosis was suspected. The patients, as well as the general practitioners, initially thought that the skin lesions were related to the infections rather than the drugs. One of the patients had FDE to trimethoprim and the intensity of his reaction appeared to be dose related. As co-trimoxazole is being used more commonly, we would expect to see more FDE, even among the paediatric age group. PMID- 1416794 TI - Challenges facing the medical profession in the 1990s. PMID- 1416795 TI - Spasticity--implications in rehabilitation. AB - Several features characterise spasticity which may be present in patients with lesions of the upper motor neurones of the brain and spinal cord. Spasticity gives rise to disability depending on the site and extent of the lesion. The manifestations of spasticity and its direct consequences on the locomotor system are discussed in this paper together with the factors affecting it. Management strategies in the rehabilitation of patients with spasticity are outlined, with emphasis on preserving maximum possible function in mobility and activities of daily living. PMID- 1416796 TI - Social and cultural aspects of organ donation in Asia. AB - In Asian countries, it is more difficult to obtain cadaver kidneys for renal transplantation because of certain socio-cultural beliefs and customs. The issues affecting living related kidney donation are more social than cultural. This is due to the web of family pressures and personal conflicts for both donor and recipient surrounding the donation. Important misconceptions and fears are: fear of death, the belief that removal of organ violates sanctity of decreased, concern about being cut up after death, desire to be buried whole, dislike of idea of kidneys inside another person, wrong concept of brain death, and the idea of donation being against religious conviction. In Singapore, with the introduction of the Human Organ Transplant Act (HOTA) in 1988, the number of cadaveric transplants have increased, including those from the Medical Therapy Act (MTA). HOTA and education have played pivotal roles in bringing about an increased yield of cadaveric kidneys. With the availability of living unrelated donor (LUD) transplants in India, our living related donor (LRD) transplant programme has suffered, because patients would rather buy a kidney from overseas than get a relative to donate one. Patients are also going to China for overseas cadaveric transplants where the kidneys come from executed convicts. People in countries like Hong Kong, Japan and the Philippines share the same Asian tradition of not parting with their organs after death. Muslim countries like Malaysia require the deceased to have earlier pledged his kidneys for donation prior to death before they can be harvested for transplantation at death. PMID- 1416797 TI - Can therapeutic interventions prevent chronic renal failure? AB - One way to prevent chronic renal failure (CRF) is to institute preventive measures against renal diseases in the general population. Patients with hereditary kidney diseases should have genetic counselling. Certain infections affecting or causing kidney diseases can be eradicated. People should be cautious in the use of analgesics and non-steroidal anti-inflammatory agents. Exposure to hydrocarbons, heavy metals and toxic gases should be avoided. Proper management of diabetes mellitus, gout, renal stones and hypertension can prevent renal damage. In patients with established renal disease, the following factors if treated or modified can prevent or ameliorate renal injury: glomerular hypertension, cell mediated proliferation, lipid induced proliferation, coagulation and thrombosis. Pregnancy in patients with renal disease should be well managed and termination advised if necessary. Reversible causes of renal failure as well as acute reversible elements can be removed or treated. Acute renal failure due to toxins can be avoided, although prevention requires awareness of association with renal failure. Prevention too depends on early detection of nephrotoxic injury like: greater awareness of hazards of environmental toxins, careful monitoring of dosage of nephrotoxic drugs and when possible, total avoidance of nephrotoxins should be the rule. Finally, in patients with glomerular disease, prevention or amelioration of glomerular damage with pharmacological agents have been achieved in some instances. PMID- 1416798 TI - Medical aspects of drowning in children. AB - Accidental, homicidal and suicidal drowning comprise a special challenge to the clinician and preventive medicine advocate, alike. In South-east Asia and Australasia, accidental immersion accidents rank highly among the causes of preventable child trauma. Bath-tub and bucket drownings affect infants and toddlers under the age of 12 months, and some 10 percent of fatal bucket-tub immersions affecting infants are the result of child abuse. Immersion accidents in the sea have special characteristics, not specifically as a result of differences in water osmolarity, but related to hypothermia, secondary lung complications, and immersion times. Swimming pool drownings are the major cause of preventable death affecting pre-school children in some regions of Australasia. Resuscitation of the near-drowned child is topical because, (a) of controversies about the optimality of mouth-to-nose expired air resuscitation (EAR) in infants under six months of age; (b) of controversies about the degree of brain damage among child survivors following intensive care salvage; and (c) the difficulties of having "every parent a first-aider". A major study of childhood immersions (The Brisbane Drowning Study has shown that of all survivors, some 70 percent will be completely normal, 30 percent will suffer some selective deficit (with wide disparities on sub-scale scores on formal IQ testing), and 3 percent will live in a permanent vegetative state. Vigorous preventative campaigns using the triad of (a) public media education and campaigns, (b) better safety standards and safety devices, and (c) safety legislation, can reduce both the population risk and the individual clinical severity of immersion accidents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1416799 TI - Objective assessment of research performance. AB - Research output in academic institutions need critical and objective assessment. Publications are an important avenue by which research by an academic can be evaluated. Journals in which such publications appear may be ranked and weight age given to publications in highly ranked journals. The number of citations of an academic's work by peers is another assessment of quality of research output. Firstly subjective peer assessment although flawed by interpersonal bias has its merits especially when evaluation is by an outsider of the institution. PMID- 1416800 TI - The second Seah Cheng Siang Memorial Lecture. Clinical skills in an age of technology. PMID- 1416801 TI - Rapidly progressive autosomal dominant parkinsonism and dementia with pallido ponto-nigral degeneration. AB - We describe a family with nearly 300 members over 8 generations with 32 affected individuals who have an autosomal dominant neurodegenerative disease characterized by progressive parkinsonism with dystonia unrelated to medications, dementia, ocular motility abnormalities, pyramidal tract dysfunction, frontal lobe release signs, perseverative vocalizations, and urinary incontinence. The course is exceptionally aggressive; symptom onset and death consistently occur in the fifth decade. Positron emission tomographic studies with [18F]6-fluoro-L-dopa (6FD) were performed in 4 patients and 7 individuals at risk for development of the disease. All affected subjects had markedly reduced striatal uptake of 6FD (p less than 0.001). All individuals at risk had normal striatal uptake, but high 6FD uptake rate constants were noted in 3 of the 7 studied. Autopsy findings revealed severe neuronal loss with gliosis in substantia nigra, pontine tegmentum, and globus pallidus, with less involvement of the caudate and the putamen. There were no plaques, tangles, Lewy bodies, or amyloid bodies. This kindred appears to represent a neurodegenerative disease not heretofore described. We propose the following name for this new genetic disease: autosomal dominant parkinsonism and dementia with pallido-ponto-nigral degeneration. PMID- 1416802 TI - Spectrum of human immunodeficiency virus-associated neocortical damage. AB - A spectrum of neurocognitive defects, termed human immunodeficiency virus type 1 (HIV-1)-associated cognitive/motor complex, has been described in patients with acquired immunodeficiency syndrome (AIDS). AIDS dementia complex (ADC) is a severe form of this disease seen in 20 to 30% of terminally ill patients. The etiology of this complex is distinct from commonly observed opportunistic infections seen in brains of patients with AIDS and has been attributed to HIV infection within the brain. At autopsy, the brains of patients with ADC contain numerous HIV-infected macrophages/microglia with prominent subcortical damage, together termed HIV encephalitis. We retrospectively analyzed all 107 brains from a three-year period (1988-1990) of AIDS autopsies using immunocytochemistry to detect HIV. Rather than breaking into distinct groups of HIV encephalitis versus non-HIV encephalitis, the specimens revealed a spectrum of severity of HIV infection. Although only 16% of the brains showed the histological hallmarks of HIV encephalitis, more than 50% of the autopsies showed moderate to severe HIV infection. In a subset of 23 AIDS autopsies during which short postmortem times and absence of significant opportunistic infection permitted quantitative analysis of dendritic and synaptic complexities, we identified a strong correlation between neocortical dendritic and presynaptic damage and abundance of HIV envelope protein in the neocortical gray and deep white matter. This correlation suggests that the presence of HIV-1 in the neocortex may be responsible by direct or indirect mechanisms for dendritic and synaptic damage. PMID- 1416803 TI - Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia. AB - In the human brain, receptor binding sites for angiotensin are found in the striatum and in the substantia nigra pars compacta overlying dopamine-containing cell bodies. In contrast, angiotensin-converting enzyme occurs in the substantia nigra pars reticulata and is enriched in the striosomes of the striatum. In this study, using quantitative in vitro autoradiography, we demonstrate decreased angiotensin receptor binding in the substantia nigra and striatum of postmortem brains from patients with Parkinson's disease. In the same brains the density of binding to angiotensin-converting enzyme shows no consistent change. We propose, from these results, that angiotensin receptors in the striatum are located presynaptically on dopaminergic terminals projecting from the substantia nigra. In contrast, the results support previous studies in rats demonstrating that angiotensin-converting enzyme is associated with striatal neurons projecting to the substantia nigra pars reticulata. These findings raise the possibility that newly emerging drugs that interact with the angiotensin system, particularly converting enzyme inhibitors and new nonpeptide angiotensin receptor blockers, may modulate the brain dopamine system. PMID- 1416804 TI - Motor inhibition and excitation are independent effects of magnetic cortical stimulation. AB - We administered magnetic cortical stimulation (MCS) during voluntary contraction of intrinsic hand muscles to 8 patients with motor neuron disease (MND), 5 patients with pure lower motor neuron syndromes (LMN), a patient with severe subacute sensory neuropathy (SSN), and 10 healthy volunteers. Patients with MND had clinical evidence of upper MND and elevated thresholds for (3 patients) or absence of (5 patients) motor evoked potentials (MEPs). MCS during sustained contraction inhibited electromyographic activity in 6 of 8 patients with MND, without preceding MEPs. MCS had no effect on the electromyogram (EMG) of the other 2 patients with MND. In normal subjects and patients with LMN, inhibition of EMG was never seen without a preceding MEP, regardless of stimulus intensity. In the patient with SSN, MCS elicited normal MEPs and inhibited the EMG in a pattern similar to normal subjects, whereas supramaximal electrical stimulation of median and ulnar nerves failed to inhibit the EMG despite normal M and F responses. Our findings indicate that the inhibitory effects of MCS on EMG are not dependent solely on changes in afferent feedback caused by the muscle twitch produced by the MEP, or on Renshaw cell inhibition. We suggest that some of the inhibitory and excitatory effects of MCS on the motor system are mediated by distinct cortical elements, which may have different susceptibilities to pathophysiological processes in MND. PMID- 1416805 TI - Facilitation of responses to motor cortex stimulation: effects of isometric voluntary contraction. AB - In 7 normal subjects we compared the facilitatory effect of isometric contraction of the tibialis anterior on the size of electromyographic responses evoked in this muscle by electric stimuli applied over the cervical column and by electric and magnetic percutaneous stimulation of the motor cortex. No significant difference was found between the degrees of facilitation of the responses to any of the stimuli. Using collision techniques, we also showed that the pyramidal fibers activated by spinal and cortical stimuli are the same. Facilitation induced by isometric contraction (20% maximum) was of similar or greater magnitude than that found with constant vibration of the tendon of the target muscle. In cases where vibration and contraction had equal facilitatory effects, there was no further facilitation of the responses when both conditions were applied together. These findings indicate that the facilitatory effect of isometric contraction of the target muscle essentially originates at a spinal level rather than in the motor cortex. PMID- 1416806 TI - Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer's disease. AB - A higher prevalence of dementia in individuals with fewer years of education has suggested that education may protect against Alzheimer's disease (AD). We tested whether individuals with more years of education have a more advanced AD before it is clinically evident. As a measure of pathophysiological severity, we quantified regional cerebral blood flow (rCBF), by the 133Xenon inhalation technique; a specific pattern of flow reduction in the parietotemporal cortex corresponds to AD pathology. In 3 groups of patients with probable AD, matched for clinical measures of dementia severity but with varying levels of education, whole-cortex mean flows were comparable. However, the parietotemporal perfusion deficit was significantly greater in the group with the highest level of education, indicating that AD was more advanced in this group. We conclude that education or its covariates or both may provide a reserve that compensates for the neuropathological changes of AD and delays the onset of its clinical manifestations. PMID- 1416807 TI - Subclinical histopathological changes in the oculomotor nerve in diabetes mellitus. AB - To provide reference values for the oculomotor nerve, for example, fascicular area and myelinated fiber (MF) number and size distribution, in pathological states, and to determine whether oculomotor nerves from diabetic patients without a history of oculomotor palsy have subclinical structural alterations, the morphometric features of 15 control subjects and eight diabetic patients were evaluated at a proximal and a distal level. On average the control nerves had a fascicular area of 2.7 mm2, 22,311 MF, and a bimodal diameter distribution with peaks at approximately 5 to 6 and 10 to 11 microns and a range of 2 to 20 microns. In proximal nerve, glial bundles were found in one-half of the subjects and patients, with a peak of MF sizes that differed from fibers in nonglial areas. The nerves from diabetic patients departed from the nerves from control subjects in the following two respects: changed size distribution, suggesting atrophy of fibers, and microfasciculation of edge fibers in parts of the fascicles in one-half of the patients. We conclude that glial bundles are probably a normal variant. Microfasciculation occurred much more frequently in nerves from diabetic patients and may represent subclinical injury of unknown cause. The alteration in size distribution may reflect the diabetic state and is not necessarily a precursor to diabetic ophthalmoplegia. PMID- 1416808 TI - Felbamate monotherapy: controlled trial in patients with partial onset seizures. AB - Felbamate (FBM) monotherapy was evaluated in 44 patients with uncontrolled partial onset seizures in a unique, single-center, randomized, double-blind, parallel-group trial. During the 56-day baseline period, patients were required to have at least 8 seizures and to be receiving only one standard antiepileptic drug (AED) at a therapeutic level; a second AED was allowed if at a subtherapeutic level. Patients were randomized to valproate (VPA), 15 mg/kg, or to FBM, 3,600 mg/day. In the treatment phase, previous AEDs were discontinued by study day 28 (by one-third decrements on study days 1, 14, and 28). Study end points were completion of 112 study days or the fulfilling of escape criteria. Criteria for escape relative to baseline were: two-fold increase in monthly seizure frequency, two-fold increase in highest 2-day seizure frequency, single generalized tonic-clonic seizure (GTC) if none occurred during baseline, or significant prolongation of GTCs. The predetermined primary efficacy variable was the number of patients escaping in each treatment group. Nineteen patients on VPA and 3 on FBM met escape criteria (p less than 0.001, chi-square test). When overall seizure frequency among study completers was compared with baseline, the FBM group had a 50 to 65% reduction in seizure frequency. FBM adverse experiences were all mild or moderate in severity, and the incidence of adverse experiences was lower in monotherapy. FBM monotherapy was effective in the treatment of partial onset seizures with or without generalization and demonstrated a favorable safety profile. PMID- 1416809 TI - Clinical trial design for antiepileptic drugs. PMID- 1416810 TI - New anatomical and functional imaging methods. AB - Powerful new methods for imaging both brain anatomy and brain function are appearing at an increasing rate. The modern era of minimally invasive, highly informative, neurological diagnostic imaging methods began with the introduction of x-ray computed tomography in the 1970s. More recently, positron emission tomography and single-photon emission computed tomography have been used extensively in research on normal and pathological brain function, and they are finding specific medical applications. Nuclear magnetic resonance methods are in widespread use for neurological diagnosis only a decade after they became available. Rapid development of new techniques based on the same principles, and implementable on clinical instruments with relatively minor modifications, will expand the range of nuclear magnetic resonance measurement capabilities considerably in the near future. These technological innovations and others yet to come have major implications for the practice of neurology. The most important one is an increase in relative value among clinical diagnostic skills of history taking and mental status examination, which will remain largely beyond the reach of technology. PMID- 1416811 TI - Absence of measles, mumps, and rubella viral genomic sequences from multiple sclerosis brain tissue by polymerase chain reaction. AB - We tested for measles, mumps, and rubella viruses in multiple sclerosis by polymerase chain reaction (PCR). Using RNA extracted from 19 multiple sclerosis and 8 control brain specimens, nested PCR was performed after reverse transcription (RT) of the RNA to cDNA using primer pairs directed against two regions in the genomes of measles and mumps viruses and one region in the rubella virus genome. Despite enhanced sensitivity of nested RT PCR, measles, mumps, and rubella viral genomic sequences were not found in any brain specimen. PMID- 1416812 TI - Werdnig-Hoffmann disease and chronic distal spinal muscular atrophy with apparent autosomal dominant inheritance. AB - We report on a family in which both Werdnig-Hoffmann disease (severe infantile onset spinal muscular atrophy) and chronic distal spinal muscular atrophy occurred, with apparent autosomal dominant inheritance. The female proband clinically had Werdnig-Hoffmann disease and died at 10 months. In their second decade of life, the proband's father and his 2 brothers developed bilateral progressive atrophy and weakness of the hands and mild weakness in the distal parts of the legs. Their mother had no symptoms or signs of motor neuron disease but electromyography revealed distal denervation of the limbs. While the family studies suggest autosomal dominant inheritance, it is possible that the proband's condition was influenced by a maternally derived allelic or modifying trait. PMID- 1416813 TI - Recurrent transverse myelitis, myasthenia gravis, and autoantibodies. AB - A 45-year-old man with a longstanding diagnosis of myasthenia gravis presented with four episodes of transverse myelitis in 5 years. Each episode improved after treatment with steroids. Laboratory studies revealed no evidence of multiple sclerosis or a structural spinal lesion. He had antinuclear and anti-DNA antibodies and the HLA-A1, B8, DR3 haplotype known to be associated with certain autoimmune diseases. We propose an autoimmune cause for the recurrent episodes of myelitis. PMID- 1416814 TI - Heat shock proteins as targets for gamma-delta T cells in multiple sclerosis. PMID- 1416815 TI - Modification of muscle activity after BOTOX injections in spasmodic torticollis. PMID- 1416816 TI - Pulmonary disposition of antimicrobial agents: methodological considerations. PMID- 1416817 TI - Pulmonary disposition of antimicrobial agents: in vivo observations and clinical relevance. PMID- 1416818 TI - Effects of age and gender on pharmacokinetics of cefepime. AB - The effects of age and gender on the pharmacokinetics of cefepime were examined in 48 volunteers following administration of a single 1,000-mg intravenous dose. Male and female subjects were divided into four groups, each consisting of 12 subjects, according to their age and gender. The young subjects were between 20 and 40 years of age and elderly subjects were between 65 and 81 years of age. Serial blood and urine samples were collected from each subject and were analyzed for cefepime by validated high-pressure liquid chromatographic assays with UV detection. Key pharmacokinetic parameters were calculated by noncompartmental methods. There were no gender-related differences in elimination half-life (t1/2) and weight-normalized total body clearance (CLT), renal clearance (CLR), and steady-state volume of distribution (Vss). Statistically significant age-related effects were found for t1/2, CLT, CLR, and Vss parameters. In different study groups, Vss ranged from 0.21 to 0.24 liter/kg. The values for Vss were significant greater for elderly subjects than they were for young subjects. The cefepime t1/2 was significantly longer in elderly subjects (about 3 h) than that observed in young subjects (about 2.2 h). The mean values for CLT and CLR in the four study groups ranged from 1.11 to 1.56 and 0.99 to 1.44 ml/min/kg, respectively. In elderly subjects, the estimates for CLT and CLR were significantly lower than those observed in young subjects. Linear regression revealed good correlations between clearance values of cefepime and creatinine. The magnitude of age-related changes in the pharmacokinetics of cefepime is not significant enough to recommend dosage adjustment in elderly patients with kidney functions normal for their age. PMID- 1416819 TI - Efficacy of erythromycin lactobionate for treating Pseudomonas aeruginosa bacteremia in mice. AB - We induced endogenous Pseudomonas aeruginosa bacteremia by administering cyclophosphamide and ampicillin to specific pathogen-free mice fed P. aeruginosa. Using this model, we evaluated the efficacy of erythromycin lactobionate (EML) in treating P. aeruginosa bacteremia. Treatment with EML at 50 and 100 mg/kg of body weight per day twice a day for 14 days significantly increased the survival rate. The most effective dose was 100 mg/kg/day, with a survival rate of 80% compared with a 20% survival rate in the control. However, the administration of EML at 500 mg/kg/day rather decreased the survival rate. In a model of intravenous infection, treatment with EML at 100 mg/kg/day twice a day for 7 days before the bacterial challenge also enhanced the survival rate. EML levels in serum, liver, and stool were apparently lower than the MIC (512 micrograms/ml). These observations suggest that EML is effective against P. aeruginosa bacteremia despite a lack of specific activity for this pathogen. Although the protective mechanism is still unclear, it is possible that a subinhibitory level of EML may affect the virulence of P. aeruginosa and enhance the host defense system. PMID- 1416820 TI - Dynamic interactions of biofilms of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin. AB - The dynamic interaction of planktonic and biofilm cells of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin was investigated in a chemostat system. The results indicated that planktonic and young biofilm cells of the 2 day-old chemostat culture of P. aeruginosa were susceptible to killing by chemostat-controlled doses of either 250 micrograms of piperacillin per ml plus 5 micrograms of tobramycin per ml or 500 micrograms of piperacillin per ml plus 5 micrograms of tobramycin per ml. Complete eradication of the planktonic and young biofilm cells was observed after exposure of the cells to six chemostat controlled doses of these antibiotic at 8-h intervals for 7 days. Regrowth of the organism was not observed after the termination of antibiotic therapy on day 7. A different picture was observed when antibiotic treatment was initiated on day 10 after inoculation. Viable old biofilm cells were reduced to approximately 20% after exposure to the chemostat-controlled doses of 500 micrograms of piperacillin per ml plus 5 micrograms of tobramycin per ml. Complete eradication of old biofilm cells could not be achieved, and regrowth of the organism occurred after the termination of antibiotic therapy. These data suggest that young biofilm cells of mucoid P. aeruginosa can be effectively eradicated with the combination of piperacillin and tobramycin, while old biofilm cells are very resistant to these antibiotics and eradication of old biofilm cells is not achievable with the chemostat-controlled doses of piperacillin and tobramycin used in this study. PMID- 1416821 TI - Combined effect of fluconazole and recombinant human interleukin-1 on systemic candidiasis in neutropenic mice. AB - The aim of the present study was to investigate the efficacy of treatment with a combination of fluconazole and human recombinant interleukin-1 alpha (IL-1 alpha) in normal or neutropenic mice with systemic Candida albicans infection. Six hours after intravenous injection of 5 x 10(4) CFU of C. albicans organisms, oral treatment twice daily with 2.5 or 10 mg of fluconazole per kg of body weight, a single intraperitoneal injection of 80 ng of IL-1, or a combination of the two was started. IL-1 had no influence on the antifungal activity of fluconazole in vitro or on the pharmacokinetics of fluconazole. For both normal and neutropenic mice, the number of C. albicans organisms cultured from the kidneys after 36 h of treatment was significantly lower in mice treated with IL-1 alone than in untreated animals. Treatment with fluconazole alone also significantly lowered the number of C. albicans organisms in the kidneys compared with that in untreated controls. In normal mice, the combination of fluconazole and IL-1 was not better than fluconazole alone. In neutropenic mice, combined treatment with IL-1 and 10 mg of fluconazole per kg led to significantly lower numbers of C. albicans organisms in the kidneys and the spleen than treatment with either agent alone. Although the precise mechanism by which IL-1 enhances resistance to infection is not clear, the additive effect of IL-1 and fluconazole in vivo indicates that combined therapy with immunomodulators and antifungal drugs is beneficial in immunocompromised mice with systemic fungal infections. PMID- 1416822 TI - Practical computer-assisted dosing for aminoglycoside antibiotics. AB - In principle, computer-assisted individualization of antibiotic dosing offers the prospect of better patient outcomes through improved dosing precision. In practice, however, the expertise in pharmacokinetics required to operate these programs has precluded their use by most physicians and pharmacists. We developed a computer program for individualization of dosing of aminoglycoside antibiotics under conditions in which access to experts in pharmacokinetics is impractical. The program is accurate, yet it requires less effort for data collection than previous drug dosing programs did. The program generates advice on a broad spectrum of topics, including dose adjustment, interpretation of measured drug concentrations in blood, and recommendations for monitoring drug concentrations. We tested its performance by prospectively comparing it with a clinical pharmacokinetic consultation service in a series of 78 consecutive patients. There were no differences in accuracy or bias in the prediction of drug concentrations. The rate of agreement between the program's dosing recommendations and those of the consultation service was 67 percent. This rate of agreement is typical of interexpert variation. In a stratified set of 24 of the 41 instances with significant disagreement regarding the recommended dose, experts ranked the program's recommendations as highly as those of the consultation service (95% confidence interval for difference in rank, -0.30 less than chi less than 0.47). The results suggest that expert systems can be coupled with pharmacokinetic dosing programs to deliver high-quality clinical recommendations for administration of antimicrobial agents. PMID- 1416823 TI - Therapy of Rhodococcus equi disseminated infections in nude mice. AB - Rhodococcus equi is a facultative, intracellular, gram-positive coccobacillus increasingly reported as an opportunistic pathogen in human immunodeficiency virus-positive patients. However, the optimal drug regimen for treating R. equi pulmonary or systemic infections is not yet known. Therefore, a model of intravenously infected nude mice with disseminated infection was created to study the efficacy of antibiotics alone or in combination as determined by the reduction of bacterial CFU per gram in the lungs and spleen after 4 and 11 days of treatment. The studied antibiotics possessing low MICs against R. equi strains were amikacin, ciprofloxacin, erythromycin, imipenem, minocycline, rifampin, and vancomycin. Vancomycin, imipenem, and rifampin were the most effective agents in monotherapy. On the other hand, amikacin, ciprofloxacin, erythromycin, and minocycline alone were not active in this model. The most active drug combinations were those including vancomycin. No antibiotic-resistant mutants were selected in vivo with treatment involving any drugs used alone or in combination. Although the treatment recommended until now for R. equi infections is rifampin plus erythromycin, this study suggests that antibiotic combinations which include vancomycin may be the most effective in vivo. PMID- 1416824 TI - Teicoplanin versus vancomycin for prophylaxis of experimental Enterococcus faecalis endocarditis in rats. AB - Teicoplanin was compared with vancomycin for the prophylaxis of experimental Enterococcus faecalis endocarditis in rats. Single intravenous doses of teicoplanin (7 mg/kg of body weight) or vancomycin (15 mg/kg) were given 30 min before bacterial challenge. Two strains of E. faecalis (309 and 1209) isolated from patients with endocarditis were tested. Bacterial inocula ranged from 10(4) (i.e., the inoculum infecting 90% of the control rats [ID90]) to 10(7) CFU/ml. The MICs and MBCs of teicoplanin and vancomycin were, respectively, 0.25 to greater than 128 mg/liter and 2 to greater than 128 mg/liter for strain 309 and 0.5 to greater than 128 mg/liter and 0.5 to greater than 128 mg/liter for strain 1209. Vancomycin prevented endocarditis only in 60% (strain 309) and in 87% (strain 1209) of rats challenged with the smallest bacterial-inoculum size (ID90), whereas teicoplanin prevented endocarditis in 100% of rats challenged with the same inoculum (strain 309; P = 0.05), in 87% of rats challenged with 10 times the ID90 (strain 309; P = 0.02), and in 95% of rats challenged with 100 times the ID90 (strain 1209; P = 0.0003). The combination of teicoplanin plus gentamicin (4 mg/kg) extended the protection to inocula 100 times the ID90 (strain 309; 96% of sterile animals) and 1,000 times the ID90 (strain 1209; 100% of sterile animals). Prevention of endocarditis was likely to be due to a prolonged inhibition of bacterial growth by sustained levels of teicoplanin in serum and not to bacterial killing. Indeed, teicoplanin did not exhibit any bactericidal activity either in vitro (time-kill curves) or in vivo (serum bactericidal activity). Teicoplanin proved to be superior to vancomycin in the prophylaxis of experimental E. faecalis endocarditis in rats. PMID- 1416825 TI - Effects of magainins on ameba and cyst stages of Acanthamoeba polyphaga. AB - Amebic keratitis produced by Acanthamoeba spp. is an increasingly important ocular infection in extended-use contact lens wearers. Problems associated with the infection are compounded by the lack of effective and well-tolerated chemotherapeutic agents. The magainins, a group of naturally occurring and synthetic membrane-active peptide compounds, have been shown to be active in vitro against a clinical isolate of Acanthamoeba polyphaga. Two magainins tested extensively had minimal inhibitory and minimal amebicidal values of 20 and 25 micrograms/ml for magainin MSI-103 and 25 and 40 micrograms/ml for magainin MSI 94, respectively. Both amebastatic and amebicidal activities are enhanced by combining the magainins with silver nitrate (200 micrograms/ml) and/or other marginally effective antimicrobial agents. These combinations have activity against both trophic and cystic stages in the Acanthamoeba life cycle and have promise as antimicrobial agents in the treatment of amebic keratitis. PMID- 1416826 TI - Continuous intravenous versus intermittent ampicillin therapy of experimental endocarditis caused by aminoglycoside-resistant enterococci. AB - We studied the efficacy of continuous intravenous infusion of ampicillin compared with that of intermittent administration of ampicillin alone or in combination with gentamicin for the therapy of highly aminoglycoside-resistant enterococcal experimental endocarditis. Rabbits were infected with a gentamicin-susceptible (MIC, 256 micrograms/ml) strain of Enterococcus faecalis or a strain of E. faecalis which was highly resistant to gentamicin in vitro (MIC, greater than 2,000 micrograms/ml). Administration of ampicillin by continuous intravenous infusion did not significantly enhance the killing of enterococci in vivo compared with that by intermittent administration of ampicillin for either the aminoglycoside-susceptible or the aminoglycoside-resistant strain. In combination with gentamicin, there were no significant differences in efficacies obtained with intermittent versus continuous intravenous infusion of ampicillin therapy for experimental endocarditis caused by either strain of E. faecalis. PMID- 1416827 TI - High-performance liquid chromatographic method for potency determination of amoxicillin in commercial preparations and for stability studies. AB - A reversed-phase column liquid chromatographic method was developed for the assay of amoxicillin and its preparations. The linear calibration range was 0.2 to 2.0 mg/ml (r = 0.9998), and recoveries were generally greater than 99%. The high performance liquid chromatographic assay results were compared with those obtained from a microbiological assay of bulk drug substance and capsule, injection, and granule formulations containing amoxicillin and degraded amoxicillin. At the 99% confidence level, no significant intermethod differences were noted for the paired results. Commercial formulations were also analyzed, and the results obtained by the proposed method closely agreed with those found by the microbiological method. The results indicated that the proposed method is a suitable substitute for the microbiological method for assays and stability studies of amoxicillin preparations. PMID- 1416828 TI - Impact of bioavailability on determination of the maximal tolerated dose of 2',3' dideoxyinosine in phase I trials. AB - The objective of this study was to determine the population pharmacokinetic parameters and the extent of absorption of 2',3'-dideoxyinosine, a nucleoside analog with activity against human immunodeficiency virus in vitro and in vivo, after oral and intravenous administration through the use of NON-linear Mixed Effects Modeling. The data were drawn from the pharmacokinetics section of an open-label, multicenter phase I study. One center administered ddI on a once daily schedule. The other centers administered the drug once every 12 h. Drug was administered intravenously, and the plasma concentration-time profile was determined. Patients were then given the drug orally at twice the dose used in the intravenous portion of the study, and the pharmacokinetic profile was again determined. A 40-fold range of doses was examined. Forty-six human immunodeficiency virus-infected patients were studied. Concentrations in plasma were determined by high-pressure liquid chromatography. Clearance of the drug from plasma was 47.7 liters/h/70 kg of body weight. The terminal half-life was 1.4 h. The volume of distribution in the central compartment was 18.8 liters/70 kg. Absorption was rapid, with an absorption half-life of 0.52 h. Bioavailability with once-daily administration was 27%. For twice-daily administration, bioavailability rose to 36%. This difference was significant (P much less than 0.01). For doses of less than or equal to 5.1 mg/kg given every 12 h (10.2 mg/kg/day), bioavailability was 41%. We conclude that once-daily administration results in lower mean bioavailability, probably because of a saturation of the absorption process similar to that seen with acyclovir. This difference in bioavailability on the basis of the administration schedule explains the different short-term maximal tolerated doses identified in phase I trials of this agent. PMID- 1416829 TI - Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo. AB - Nikkomycins X and Z (NZ), competitive inhibitors of fungal chitin synthetase, were combined with azoles in a series of in vitro checkerboard assays to test for synergism against Candida spp. All combinations of nikkomycins and azoles tested resulted in marked synergistic activity against an isolate of Candida albicans, with fractional inhibitory concentration indices ranging from 0.016 to 0.28. No synergistic effect was demonstrable with isolates of C. tropicalis, C. parapsilosis, or C. krusei, though results for the latter two were suggestive of an additive effect. In survival models of mice infected intravenously with C. albicans, NZ administered singly in doses ranging from 5 to 50 mg/kg of body weight twice a day was able to delay the onset of mortality but showed no dose response effect. The combination of NZ and the azole R 3783 administered orally in a ratio of 8:1 to 40:1 or greater (wt/wt) enhanced survival better than did the drugs given individually, but this effect was less evident for combinations involving fluconazole. In short-term organ load assays with outbred mice infected intravenously with C. albicans, high ratios of NZ to R 3783 reduced the CFU per gram in kidneys more significantly than did the drugs individually. Statistically significant reductions were not seen for short-term fungal burden assays using combinations of NZ and fluconazole in outbred mice or in inbred mice more susceptible to candidiasis. In a model of rat vaginal candidiasis, the combination of NZ and R 3783 administered either orally or vaginally was more effective than the drugs used singly. Thus, under certain conditions, combination therapy with nikkomycin and select azoles may offer promise for an increased therapeutic effect in candidiasis. PMID- 1416830 TI - Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection. AB - The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infection in burned mice, while it was much less active against intraperitoneal infection in normal mice. In a burn infection model, IN-2A8 inhibited the increase of bacteria in skin lesions weakly and that in blood significantly, suggesting that it strongly suppressed bacterial spread to blood. The activity of IN-2A8 in combination with 10 antipseudomonal antibiotics against intraperitoneal infection was examined. Clear additive effect was observed with a combination of either carbapenem or aminoglycoside antibiotics in terms of mouse survival. The administration of an antibiotic, imipenem-cilastatin, simultaneously with or before that of IN-2A8 gave a combined effect, but the reverse order did not. The combination of IN-2A8 with imipenem-cilastatin decreased numbers of viable bacteria in the peritoneal cavity and blood and kept them low for a longer time than did either treatment alone. These results suggest that an antiflagellar monoclonal antibody would be effective against systemic infection in combination with some kinds of antibiotics. PMID- 1416831 TI - Mycolic acid synthesis: a target for ethionamide in mycobacteria? AB - Striking structural analogies exist between the two specific antimycobacterial drugs ethionamide (ETH) and isoniazid (INH), and they share several inhibitory properties in susceptible species of mycobacteria. The effect of ETH on mycolic acid synthesis was studied in whole cells and in cell extracts of various species, since this synthesis is one direct target for INH, as we recently demonstrated in cell extracts of Mycobacterium aurum. It was shown in the present study that there is not a direct relationship between ETH susceptibility and mycolic acid inhibition. This observation could explain the lack of cross resistance between the two drugs. The presence of ETH disturbed mycolic acid synthesis in both resistant and susceptible mycobacteria. Synthesis of oxygenated species of mycolic acid was inhibited, while that of diunsaturated acids was either slightly altered or even increased. In contrast, INH inhibited the synthesis of all kinds of mycolic acids in the same way in all susceptible strains and had no effect on mycolic acid synthesis in resistant strains. In the presence of ETH, the unsaturated mycolic acid molecules presented a methyl end different from the usual one. These data strongly suggest that the normal unsaturated mycolic acid species are not the precursors of the oxygenated types. Moreover, they show that ETH probably acts early in the pathway leading to oxygenated mycolic acid. PMID- 1416832 TI - Antimycoplasmal activities of new quinolones, tetracyclines, and macrolides against Mycoplasma pneumoniae. AB - Fifty strains of Mycoplasma pneumoniae were tested for susceptibility to new quinolones, tetracyclines, and macrolides. Temafloxacin, ofloxacin, and ciprofloxacin possessed the most mycoplasmacidal activity against these organisms. The MBC for 50% of the strains (MBC50)-to-MIC50 ratio for each of these drugs was 4. The MBC50-to-MIC50 ratios for the tetracyclines and macrolides were markedly higher, within a range of 32 to 2,000. On the basis of these results, temafloxacin and ofloxacin might be promising antimicrobial agents for the treatment of mycoplasmal infection. PMID- 1416833 TI - Antimicrobial susceptibilities of a Corynebacterium CDC group I1 strain isolated from a patient with endocarditis. AB - We encountered a case of native valve endocarditis due to Corynebacterium CDC group I1 which was successfully controlled with antimicrobial agents alone. This organism and three other isolates of this group were susceptible to penicillin, vancomycin, and gentamicin. The combination of penicillin with subinhibitory concentrations of gentamicin resulted in a 1,000-fold decrease in CFU per milliliter at 24 h compared with penicillin alone. Augmentation of killing was noted also with vancomycin plus gentamicin but to a degree that did not meet strict criteria for bactericidal synergism. PMID- 1416835 TI - In vitro activity and susceptibility to hydrolysis of S-1006. AB - The in vitro activity of S-1006, the active component of a new orally absorbed cephalosporin, S-1108, inhibited 90% of Staphylococcus aureus isolates at less than or equal to 2 micrograms/ml, 90% of group A, B, C, F, and G streptococci and Streptococcus pneumoniae isolates at less than or equal to 0.12 microgram/ml, and all Haemophilus influenzae isolates at less than or equal to 0.06 microgram/ml. Although 50% of the members of the family Enterobacteriaceae were inhibited by less than or equal to 2 micrograms of S-1006 per ml, Enterobacter spp. and Citrobacter freundii resistant to ceftriaxone were resistant to S-1006. The MICs of S-1006 for approximately 20% of Providencia, Proteus vulgaris, and Serratia isolates were 4 micrograms/ml. S-1006 was hydrolyzed by the plasmid TEM-3, TEM-5, PSE-1, and PSE-4 beta-lactamases and by the chromosomal beta-lactamase of Enterobacter and Morganella spp. and P. vulgaris. PMID- 1416834 TI - Effects of antibiotics and other drugs on toxin production in Clostridium difficile in vitro and in vivo. AB - In an attempt to understand more completely why patients treated with phenothiazines (chlorpromazine and cyamemazine), methotrexate, and certain antibiotics such as clindamycin have an increased risk of developing pseudomembranous colitis, the production of toxins A and B by Clostridium difficile in the presence of these drugs was measured in vitro as well as in vivo by using axenic mice. None of the drugs tested increased the production of toxins either in vitro or in vivo. PMID- 1416836 TI - Deleterious effect of trimethoprim-sulfamethoxazole in Mediterranean spotted fever. PMID- 1416837 TI - Failure to adopt new interpretive criteria for ticarcillin-clavulanic acid could prove fatal. PMID- 1416839 TI - Increased resistance to amikacin in a neonatal unit following intensive amikacin usage. AB - Gram-negative isolates from blood and cerebrospinal fluid were monitored for 1 year before and for 1 year after the first-line aminoglycoside in a busy pediatric department was changed from gentamicin to amikacin. In the general pediatric wards, the switch to amikacin resulted in no change in resistance of nosocomial gram-negative infections to either amikacin (0% before and after) or gentamicin (23.9% [before] versus 26.5% [after]). In the neonatal unit, the switch to amikacin was followed by an outbreak of Serratia spp. that were commonly resistant to amikacin but susceptible to gentamicin. This outbreak abated spontaneously. In the year after the change in aminoglycoside usage, the resistance to amikacin of nosocomially acquired gram-negative infections increased from 7.6 to 27.7% (P less than 0.001), and the resistance to gentamicin decreased from 71.2 to 60.2% (P = 0.07). The increase in amikacin resistance of gram-negative bacilli other than Serratia spp. has persisted for more than a year after the introduction of amikacin as the sole aminoglycoside. The different effects observed in the two sections of the pediatric department may be related to the more intensive usage of aminoglycosides in the neonatal unit. PMID- 1416838 TI - Resistance of herpesviruses to antiviral drugs. PMID- 1416840 TI - Quinolone accumulation in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. AB - The accumulation of quinolones by Escherichia coli JF568, Pseudomonas aeruginosa PAO1, and Staphylococcus aureus ATCC 29213 was measured by a modified fluorometric assay (J. S. Chapman and N. H. Georgopapadakou, Antimicrob. Agents Chemother. 33:27-29, 1989). The quinolones examined were fleroxacin, pefloxacin, norfloxacin, difloxacin, A56620, ciprofloxacin, ofloxacin, and Ro 09-1168. In all three organisms, uptake was complete in less than 5 min and was proportional to extracellular quinolone concentrations between 2 and 50 micrograms/ml, which is consistent with simple diffusion. Washing cells with quinolone-free buffer decreased accumulation by up to 70% in E. coli and P. aeruginosa but not in S. aureus. Similarly, incubation with the uncouplers 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone increased accumulation up to fourfold in E. coli and P. aeruginosa, though not in S. aureus, suggesting endogenous, energy dependent efflux. High quinolone hydrophobicity was generally associated with decreased accumulation in E. coli and P. aeruginosa (except in the case of pefloxacin) but was associated with increased accumulation in S. aureus (except in the case of difloxacin). Ciprofloxacin had the highest accumulation in E. coli and P. aeruginosa, while pefloxacin had the highest accumulation in S. aureus. PMID- 1416841 TI - Liquid chromatographic determination of ampicillin in bovine and dog plasma by using a tandem solid-phase extraction method. AB - The determination of ampicillin in plasma and serum by reversed-phase high performance liquid chromatography with UV detection suffers from poor selectivity and sensitivity. Currently, the most common approach to overcoming these problems consists of improving the compound's detectability via pre- or postcolumn derivatization. In the method that we describe, however, enhanced selectivity is afforded by sample purification by a tandem solid-phase extraction method (ion exchange and reversed-phase). This approach permits detection at wavelengths of as low as 210 nm, which results in enhanced sensitivity (detection limit, 0.01 microgram/ml). A second factor that affects selectivity is the addition to the chromatographic eluent of a crown ether to optimize the separation between ampicillin and polar endogenous plasma constituents. This combination of improved sample pretreatment and a more selective chromatographic system in conjunction with internal standardization forms the basis of a new assay for the quantitation of ampicillin in plasma. The overall recovery of ampicillin was 76.4% +/- 4.9% (n = 24), and the within-run and between-run coefficients of variation ranged from 1.6 to 7.2%. The method was applied to pharmacokinetic studies in cows and dogs after intramuscular or oral administration of the drug. PMID- 1416842 TI - Evaluation of cefuroxime axetil and cefadroxil suspensions for treatment of pediatric skin infections. AB - A randomized, single-blind, multicenter study was conducted to evaluate the safety and efficacy of cefuroxime axetil and cefadroxil suspensions for the treatment of skin or skin structure infections in 287 children. Each drug was given at a dosage of 30 mg/kg of body weight per day in two divided doses. Staphylococcus aureus and Streptococcus pyogenes, or a combination of the two, were the primary pathogens isolated from infected skin lesions. A satisfactory bacteriological response (cure or presumed cure) was obtained in 97.1 and 94.3% of children in the cefuroxime axetil and cefadroxil groups, respectively (P greater than 0.05). Satisfactory clinical responses (cure or improvement) were more likely to occur in cefuroxime axetil recipients than in cefadroxil recipients (97.8 versus 90.3%; P less than 0.05). Both regimens were equally well tolerated, with adverse events occurring in 7.9 and 6.1% of cefuroxime axetil and cefadroxil recipients, respectively. There were more patients who refused to take cefuroxime axetil (7 of 189) than there were who refused to take cefadroxil (0 of 98), but the difference was not statistically significant (P = 0.1). In this study, cefuroxime axetil was at least as effective as cefadroxil in resolving skin and skin structure infections in children. PMID- 1416843 TI - Innovative endpoint determination system for antifungal susceptibility testing of yeasts. AB - Fungal infections and antifungal resistance are increasingly recognized. Antifungal susceptibility testing remains unstandardized, and a particularly important problem is endpoint determination. In this paper we propose the yeast metabolic reduction of the tetrazolium salt 2,3-bis(2- methoxy-4-nitro-5 sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetraz olium hydroxide (XTT) as a colorimetric endpoint which is quantitative and objective. Amphotericin B, fluorocytosine, and fluconazole dose-response curves were obtained, and a metabolic MIC could be determined by using precise criteria. PMID- 1416844 TI - Susceptibility testing of clinical isolates of Methylobacterium species. AB - Methylobacterium species represent a relatively new genus which is being increasingly isolated from cases of opportunistic infections. This study reports on 3 reference strains and 15 clinical isolates of Methylobacterium species. Susceptibility tests were performed by the agar dilution and commercial broth microdilution methods at both 30 and 35 degrees C. Readings were made at 24, 48, and 72 h. Incubation conditions of 48 h and 30 degrees C were found to be optimum. Both the agar dilution and broth microdilution methods gave equivalent results. Drugs tested and their MICs for 90% of isolates (in micrograms per milliliter) were as follows: amikacin, less than or equal to 1; gentamicin, 1; ciprofloxacin, 1; trimethoprim-sulfamethoxazole, 2/38; ceftriaxone, 16; and ceftizoxime, 16. The majority of our isolates were resistant to six other beta lactam drugs tested. Nine of the 15 Methylobacterium isolates were beta-lactamase positive. PMID- 1416845 TI - Correlation between in vitro antimicrobial susceptibilities and beta-lactamase plasmid contents of isolates of Haemophilus ducreyi from the United States. AB - We determined the susceptibilities of 94 strains of Haemophilus ducreyi isolated in various municipalities in the United States between 1982 and 1989 to the following antimicrobial agents: amoxicillin-clavulanic acid, ceftriaxone, erythromycin, azithromycin, ciprofloxacin, ofloxacin, trimethoprim, and spectinomycin. Ceftriaxone (MIC, less than or equal to 0.008 micrograms/ml), azithromycin (MIC, less than or equal to 0.125 micrograms/ml), erythromycin (MIC, less than or equal to 0.125 micrograms/ml), ciprofloxacin (MIC, less than or equal to 0.25 micrograms/ml), and ofloxacin (MIC, less than or equal to 0.25 micrograms/ml) were highly active against all isolates. Amoxicillin-clavulanic acid (MICs, 0.25 to 8.0 micrograms/ml), trimethoprim (MICs, 0.06 to 16.0 micrograms/ml), and spectinomycin (MICs, 2.0 to greater than or equal to 32.0 micrograms/ml) were less active against these isolates. Isolates possessing the 5.7-MDa beta-lactamase plasmid were less susceptible to erythromycin, trimethoprim, and spectinomycin than were isolates possessing the 3.2-MDa beta lactamase plasmid. The susceptibilities of plasmidless isolates to erythromycin, trimethoprim, and spectinomycin were distributed bimodally; the median MIC for the more susceptible plasmidless isolates corresponded to that for isolates with the 3.2-MDa plasmid, and the median MIC for the less susceptible plasmidless isolates corresponded to that for isolates with the 5.7-MDa plasmid. Thus, plasmid profiles may be valuable markers for geographical variations in antimicrobial susceptibilities of H. ducreyi strains that may indicate the relative efficacy of regimens for the treatment of chancroid. Of the regimens recommended by the U.S. Public Health Service for the treatment of chancroid, our results support the use of erythromycin, ceftriaxone, and ciprofloxacin, and perhaps ofloxacin, but suggest that amoxicillin-clavulanic acid and sulfamethoxazole-trimethoprim should be used with caution. PMID- 1416846 TI - In vitro study of anticancer acridines as potential antitrypanosomal and antimalarial agents. AB - The requirement for rational drug design in the search for new agents that are active against parasitic protozoa prompted our in vitro studies with a group of 9 anilinoacridines. In vitro growth assays with Trypanosoma lewisi identified a series of C-1' alkylaminoacridines which possess previously unreported potent growth-inhibitory activities against T. lewisi at a concentration range of 0.1 to 1 microM. In contrast, several 9-anilinoacridines that possess acridine ring NH2 substituents at C-3 and C-6 were inactive against T. lewisi, but they possessed strong activity against Plasmodium falciparum at a concentration range of 0.1 to 2.8 microM. In mammalian cells, amsacrine [4'-(9-acridinylamino)methanesulfon-m anisidide] inhibits DNA topoisomerase II; however, amsacrine was only weakly active against T. lewisi. Such differences in the patterns of susceptibility of mammalian cells, T. lewisi, and P. falciparum to these 9-anilinoacridines may reflect enzyme differences between different parasites and mammalian cells that can be exploited by further improvements in drug design. PMID- 1416847 TI - In vitro antifungal activities and in vivo efficacies of 1,3-beta-D-glucan synthesis inhibitors L-671,329, L-646,991, tetrahydroechinocandin B, and L 687,781, a papulacandin. AB - The in vivo anti-Candida activities of 1,3-beta-D-glucan synthesis inhibitors L 671,329, L-646,991 (cilofungin), L-687,901 (tetrahydroechinocandin B), and L 687,781 (a papulacandin analog) were evaluated by utilizing a murine model of disseminated candidiasis that has enhanced susceptibility to Candida albicans but increased sensitivity for discriminating antifungal efficacy. DBA/2 mice were challenged intravenously with 1 x 10(4) to 5 x 10(4) CFU of C. albicans MY1055 per mouse. Compounds were administered intraperitoneally at concentrations ranging from 1.25 to 10 mg/kg of body weight twice daily for 4 days. At 6 h and 1, 2, 3, 4, 7, and 9 days after challenge, five mice per group were sacrificed and their kidneys were homogenized and plated for enumeration of Candida organisms (CFU per gram). Progressiveness of response trends and no-statistical significance-of-trend doses were derived to rank compound efficacy. 1,3-beta-D Glucan synthesis 50% inhibitory concentrations were determined by using a C. albicans (MY1208) membrane glucan assay. Candida and Cryptococcus neoformans MICs and minimal fungicidal concentrations were determined by broth microdilution. L 671,329, L-646,991, L-687,901, and L-687,781 showed similar 1,3-beta-D-glucan activities, with 50% inhibitory concentrations of 0.64, 1.30, 0.85, and 0.16 micrograms/ml, respectively. Data from in vitro antifungal susceptibility studies showed that L-671,329, L-646,991, and L-687,901 had similar MICs ranging from 0.5 to 1.0 micrograms/ml, while L-687,781 showed slightly higher MICs of 1.0 to 2.0 micrograms/ml for C. albicans MY1055. Lipopeptide compounds were ineffective against C. neoformans strains. Results from in vivo experiments comparing significant trend and progressiveness in response analyses indicated that L 671,329 and L-646,991 were equipotent but slightly less active than L-687-901, while L-687,781 was ineffective at 10 mg/kg. Fungicidal activities of L-671,329, L-646,991, and L-687,901 were observed in vivo, with significant reduction in Candida CFU per gram of kidneys compared with those in sham-treated mice at doses of > or = 2.5 mg/kg evident as early as 1 day after challenge. PMID- 1416848 TI - Antimicrobial susceptibility testing of Bilophila wadsworthia by using triphenyltetrazolium chloride to facilitate endpoint determination. AB - Initial susceptibility studies of Bilophila wadsworthia indicated significant resistance to several beta-lactam antibiotics, including imipenem and cefoxitin. NO beta-lactamase production was detected. However, some B. wadsworthia strains may grow as a heavy "haze" at up to the highest concentration of an antibiotic on standard antimicrobial agent-containing plates, and it is often difficult to determine the point at which conventional growth stops and haze growth begins. We investigated the nature of the haze growth of B. wadsworthia by using triphenyltetrazolium chloride (TTC) as an indicator of viability during antimicrobial susceptibility testing, by determining viability counts on antimicrobial agent-containing plates at various times, and by microscopically inspecting stained preparations of the growth on the control plate and the haze area. TTC MICs were determined by applying a TTC solution over the growth on plates inside the anaerobic chamber or within 5 min after exposure to air (aerobic TTC MICs). The haze growth reduced TTC in the chamber but not under aerobic conditions, whereas TTC was reduced by the conventional growth in both atmospheres. The aerobic TTC MICs correlated with the viability counts. Separated proteins resolved by polyacrylamide gel electrophoresis and isoelectric focusing showed TTC-reactive bands only when stained under anaerobic conditions, further demonstrating the sensitivity of TTC reduction to aerobic conditions. Microscopic examination of the haze growth indicated spheroplast formation. A new antibiogram for B. wadsworthia has been established by use of aerobic TTC endpoints; we believe that the lower MICs obtained with the TTC method are likely the ones that are clinically relevant and should be used in tests of B. wadsworthia. Also, we found that when the organisms were grown on pyruvate-containing medium, 87% of 56 strains tested were Beta-lactamase positive. PMID- 1416849 TI - Platelet microbicidal protein enhances antibiotic-induced killing of and postantibiotic effect in Staphylococcus aureus. AB - The interaction of bacteria with platelets at the cardiac valve surface represents a critical event in the induction of infective endocarditis. Platelets are thought to modulate induction or propagation of endocarditis via secretion of alpha-granule-derived platelet microbicidal protein (PMP) (a low-molecular-mass, cationic, heat-stable protein distinct from lysozyme). We studied representative PMP-susceptible and PMP-resistant Staphylococcus aureus isolates to determine their in vitro bacteriostatic and bactericidal susceptibilities to combinations of PMP plus antistaphylococcal antibiotics. PMP plus oxacillin exerted a synergistic bactericidal effect, in contrast to either agent alone, regardless of the intrinsic PMP susceptibility of the isolate tested. Exposure of S. aureus to PMP alone resulted in residual postexposure growth-inhibitory effects lasting from 0.9 to 1.8 h. Sequential exposure of S. aureus isolates to PMP for 30 min followed by exposure to either oxacillin or vancomycin (each at 10x the MIC for 120 min) resulted in a significant extension of the postantibiotic-effect duration compared with antibiotic exposure alone (P less than or equal to 0.05). Collectively, these findings indicate that PMP both enhances antibiotic-induced killing of S. aureus and increases the postantibiotic-effect duration in S. aureus. PMID- 1416850 TI - Resistance to cefotaxime and seven other beta-lactams in members of the family Enterobacteriaceae: a 3-year survey in France. AB - During the second quarter each of 1988, 1989, and 1990, a French collaborative study group, including 12 university hospital laboratories, surveyed the resistance to beta-lactams of clinical isolates from hospitalized patients: consecutively, 10,641, 10,692, and 9,382 isolates were tested. The distribution of bacterial species over time was similar in each laboratory. The susceptibilities of microorganisms to amoxicillin, ticarcillin, cephalothin, cefoxitin, cefotaxime (CTX), ceftazidime (CAZ), aztreonam (ATM), and imipenem (IPM) were measured by the disk diffusion method in accordance with the recommendations of the Antibiogram Committee of the French Society for Microbiology. Five reference strains were included for quality control. Extended spectrum beta-lactamases were detected by the synergistic effect of the combination of clavulanic acid-amoxicillin with CTX, CAZ, and ATM in the double diffusion test. A synergistic effect with CTX, CAZ, and ATM was detected for 1.5% of all strains, mainly those of Klebsiella pneumoniae (13.3%). For this species, the synergy test enabled the detection of roughly 50% of the resistant strains misclassified as susceptible on the basis of interpretative standards. Extended spectrum beta-lactamases disseminated in 1990 in most enterobacterial species but at a low frequency. Important variations in the percentages of resistant strains were observed in terms of bacterial species, hospitals, and wards. However, when the total number of strains was considered, the percentages of resistance to newer beta-lactams remained low. PMID- 1416851 TI - Antibiotic susceptibility survey of Neisseria gonorrhoeae in Thailand. AB - The antibiotic susceptibilities of Neisseria gonorrhoeae isolates obtained from patients attending sexually transmitted disease clinics in Cholburi and Bangkok, Thailand, were determined by agar dilution. Some 28.2% of isolates produced beta lactamase. A total of 97.9% of beta-lactamase-positive and 51% of beta-lactamase negative isolates tested were resistant to penicillin (MICs, greater than or equal to 2 micrograms/ml), 70% of isolates tested were resistant to tetracycline (MICs, greater than or equal to 2 micrograms/ml), and 91% of isolates tested were susceptible to spectinomycin (MICs, less than or equal to 64 micrograms/ml). The MICs for 90% of isolates for the other drugs tested were 2 micrograms/ml for erythromycin, 2 micrograms/ml for cefoxitin, 1 micrograms/ml for cefuroxime, 0.125 micrograms/ml for cefpodoxime, 0.06 micrograms/ml for cefotaxime, 0.25 micrograms/ml for ceftazidime, 0.03 micrograms/ml for ceftizoxime, 0.03 micrograms/ml for ceftriaxone, 0.03 micrograms/ml for cefixime, 0.06 micrograms/ml for aztreonam, 0.008 micrograms/ml for ciprofloxacin, 0.125 micrograms/ml for norfloxacin, and 0.075 micrograms/ml for ofloxacin. Fewer than 1.5% of isolates were resistant to the extended-spectrum cephalosporins tested. Some 0.3% or fewer isolates were resistant to broad-spectrum cephalosporins, fluoroquinolones, or the monobactam aztreonam. Antibiotic resistance among N. gonorrhoeae isolates from Cholburi and Bangkok in May 1990 appeared to be primarily limited to penicillin and tetracycline, which are no longer used to control gonorrhea. Spectinomycin, which has been in general use against gonorrhea in Thailand since 1983, has dwindling utility, with resistance at a level of 8.9%. PMID- 1416852 TI - Bacteriostatic and bactericidal activities of gentamicin alone and in combination with clarithromycin against Mycobacterium avium. AB - The inhibitory activity of gentamicin against Mycobacterium avium depended on the pH of the medium, and the broth-determined MICs for 90% of strains were 5.0 micrograms/ml at pH 7.4, 9.5 micrograms/ml at pH 6.8, and greater than 16.0 micrograms/ml at pH 5.0. The MBCs were two- to eightfold higher than the MICs. The combined effect of gentamicin and clarithromycin was additive, and the MICs and MBCs of each drug were either the same as those in the single-drug tests or reduced twofold. PMID- 1416853 TI - In vitro activity of MC-352, a new 16-membered macrolide. AB - The in vitro activity of MC-352, 3,4'-dideoxy-5-O-mycaminosyltylonolide, was compared with those of erythromycin, clarithromycin, and rokitamycin. The MC-352 MIC90 (MIC for 90% of isolates) for erythromycin-susceptible Staphylococcus aureus and Staphylococcus epidermidis was less than or equal to 1 microgram/ml, similar to those of the other agents. The MC-352 MIC50 for erythromycin-resistant S. aureus was 2 micrograms/ml, similar to that of rokitamycin. The MC-352 MIC90 (0.12 micrograms/ml) for Streptococcus pyogenes was similar to those of erythromycin and clarithromycin and superior to that of rokitamycin, and the MC 352 MIC90 for group B, C, and G streptococci was 0.25 microgram/ml. MC-352 and clarithromycin had an MIC90 of 0.12 microgram/ml for Streptococcus pneumoniae. Erythromycin-susceptible Enterococcus faecalis was inhibited by MC-352 at 1 microgram/ml, but the MIC for constitutively erythromycin-resistant isolates was greater than 16 micrograms/ml. Legionella pneumophila was inhibited by less than or equal to 0.25 microgram/ml. MC-352 was the most active agent against Bacteroides fragilis, with an MIC90 of 8 micrograms/ml, and was more active than the other agents against Haemophilus influenzae, with an MIC90 of 4 micrograms/ml. Moraxella spp. were inhibited by MC-352 at less than or equal to 0.25 microgram/ml. The MIC90 for Escherichia coli, Klebsiella pneumoniae, and Salmonella, Shigella, Yersinia, Enterobacter, Citrobacter, and Serratia spp. was greater than or equal to 32 micrograms/ml. MC-352 was bactericidal for S. pyogenes and S. pneumoniae, and its activity was not altered by human serum. PMID- 1416854 TI - Increased rate of isolation of penicillin-resistant Streptococcus pneumoniae in a children's hospital and in vitro susceptibilities to antibiotics of potential therapeutic use. AB - The isolation of Streptococcus pneumoniae with both high and intermediate resistance to penicillin has increased in our institution since 1989 to an average of 12.1% of all isolates. We determined the susceptibilities of 95 isolates (34 susceptible to penicillin, 42 intermediate in resistance to penicillin, and 19 resistant to penicillin) to 16 antimicrobial agents of potential use in the treatment of disease caused by S. pneumoniae. Susceptibility to penicillin was determined by broth macrodilution with Mueller-Hinton broth supplemented with 5% lysed horse blood. Isolates were classified as highly resistant when the MIC was greater than or equal to 2.0 micrograms/ml, intermediate in resistance when the MIC was between 0.1 and 1.0 microgram/ml, and susceptible when the MIC was less than 0.1 microgram/ml. Fifteen of 19 isolates found to be highly resistant to penicillin were recovered from the middle ear of children. None of the isolates recovered from cerebrospinal fluid was highly resistant to penicillin. Fifteen of these isolates highly resistant to penicillin were found to be serogroup 6. Susceptibilities to other antibiotics were determined by the agar dilution method with Mueller-Hinton agar containing 5% lysed horse blood and an inoculum of 10(4) CFU per spot delivered by a replicator device. The MIC for 90% of isolates increased with increasing penicillin resistance for all antibiotics tested, except chloramphenicol, ciprofloxacin, rifampin, and vancomycin. Regardless of the classification of penicillin resistance, all isolates were classified as susceptible to cefotaxime, cefpirome, cefpodoxime, clarithromycin, imipenem, rifampin, and vancomycin on the basis of National Committee for Clinical Laboratory Standards interpretive guidelines. Interpretation of susceptibilities on the basis of currently available guidelines is difficult in that susceptibility guidelines applicable specifically to S. pneumoniae are not available. PMID- 1416855 TI - Identification by DNA sequence analysis of a new plasmid-encoded trimethoprim resistance gene in fecal Escherichia coli isolates from children in day-care centers. AB - In our ongoing studies of trimethoprim resistance (Tmpr) in day-care centers (DCC), we have shown a high rate of fecal colonization with Tmpr Escherichia coli and, using total plasmid content analysis, have shown that this is due to a diversity of strains. In the present study, we analyzed 367 highly Tmpr (MIC, greater than or equal to 2,000 micrograms/ml) isolates of E. coli from 72 children over a 5-month period and found at least 83 distinct plasmid patterns, indicating that at least 83 strains were involved. Several strains were particularly common in a given DCC, including one found in 61% of children with Tmpr E. coli; these common strains usually persisted within a DCC for several months. Colony lysates were hybridized with gene probes for dihydrofolate reductases (DHFR) types I, II, III, V, and VII; 21% hybridized under stringent conditions, and all of these were with type I (17%) or type V (4%) probes. Tmpr was cloned from a probe-negative Tmpr transconjugant, and an intragenic probe was prepared from this clone. Approximately 21% of the Tmpr E. coli strains (76 isolates) in the DCC were found to have this new gene, 74 of which were in one DCC. The DNA sequence of this gene was determined, and the predicted amino acid sequence was shown to have between 32% and 39% identity with the amino acid sequences for types I, III, V, VI, and VII and the partial sequence of type IV and approximately 26% identity with types IX and X DHFR. This confirms the uniqueness of this gene, which has tentatively been named dhfrxii, and its translation product, DHFR type XII. PMID- 1416856 TI - Antifungal susceptibility testing of Candida spp. by relative growth measurement at single concentrations of antifungal agents. AB - The relative growth (percentage of growth relative to control growth) of 496 isolates representing six Candida species was assessed as a means of determining in vitro susceptibilities of the isolates in microdilution plate wells containing single concentrations of each of seven antifungal agents. The relative growth data were highly reproducible. With flucytosine and amorolfine they correlated well with MICs, but for an azole antifungal agent, terconazole, they did not correlate with MICs. Distributions of relative growth percentages for different Candida spp. showed significant differences in species susceptibility to individual agents. For example, C. albicans was less susceptible than the other species to amorolfine; C. parapsilosis isolates were particularly susceptible to terbinafine; and C. glabrata, C. guilliermondii, and C. krusei isolates were less susceptible than C. albicans to fluconazole and ketoconazole but equally susceptible as or more susceptible than C. albicans to itraconazole. Differential patterns of susceptibility to individual azole antifungal agents were noted for some individual strains as well as for Candida spp. PMID- 1416857 TI - Temperature-dependent in vitro antimicrobial activity of four 4-quinolones and oxytetracycline against bacteria pathogenic to fish. AB - The in vitro antimicrobial activities of oxolinic acid, flumequine, sarafloxacin, enrofloxacin, and oxytetracycline against strains of bacteria pathogenic to fish (Aeromonas salmonicida subsp. salmonicida, atypical A. salmonicida, Vibrio salmonicida, Vibrio anguillarum, and Yersinia ruckeri) were determined at two different incubation temperatures, 4 and 15 degrees C, by a drug microdilution method. The main objective of the study was to examine the effect of incubation temperature on the in vitro activities of 4-quinolones and oxytetracycline against these bacteria. When tested against A. salmonicida subsp. salmonicida, all of the quinolones examined had MICs two- to threefold higher at 4 degrees C than at 15 degrees C. Similarly, 1.5- to 2-fold higher MICs were recorded for all of the quinolones except sarafloxacin at 4 degrees C than at 15 degrees C when the drugs were tested against V. salmonicida. In contrast to those of the quinolones, the MICs of oxytetracycline were two- to eightfold lower at 4 degrees C than at 15 degrees C against all of the bacterial species tested. Of the antimicrobial agents tested against the bacterial species included in the study, enrofloxacin was the most active and oxytetracycline was the least active. Sarafloxacin was slightly more active than flumequine and oxolinic acid, especially against oxolinic acid-resistant A. salmonicida subsp. salmonicida strains. PMID- 1416858 TI - Teicoplanin metabolism in humans. AB - Teicoplanin, a lipoglycopeptide antibiotic, consists of five major components (A2 1 through A2-5), one hydrolysis component (A3-1), and four minor components (RS-1 through RS-4). All the major components contain an N-acyl-beta-D-glucosamine, but they differ in the lengths and branchings of their acyl-aliphatic chains. Previous studies with radiolabeled teicoplanin in rats and humans have shown that the drug is eliminated by the renal route and that metabolic transformation is very minor, about 5%. A possible metabolic transformation of teicoplanin into A3 1 was also suggested. In the present study in humans, two metabolites (metabolites 1 and 2; 2 to 3% of total teicoplanin) were isolated after intravenous administration of radiolabeled teicoplanin. After purification, their structures were determined by fast atom bombardment mass spectroscopy and 1H nuclear magnetic resonance spectroscopy on the basis of the well-known correlations established in this field, and they were found to be new teicoplaninlike molecules, bearing 8-hydroxydecanoic and 9-hydroxydecanoic acyl moieties. This metabolic transformation is likely due to hydroxylation in the omega-2 and omega-1 positions for metabolites 1 and 2, respectively, of the C-10 linear side chain of component A2-3. This might explain the low extent of metabolism of teicoplanin if we consider that only component A2-3 has a linear chain that is susceptible to such oxidation. PMID- 1416860 TI - Antibacterial activity of RU44790, a new N-tetrazolyl monocyclic beta-lactam. AB - RU44790 belongs to a new class of synthetic monocyclic beta-lactam antibiotics which feature a bioisosteric tetrazole moiety instead of the more classical acidic functions at the N-1 position of the beta-lactam ring. Its antibacterial activity was evaluated against some 900 strains and was compared with those of other recent beta-lactam derivatives, especially aztreonam. RU44790 is endowed with potent activity against gram-negative bacteria. At less than or equal to 0.6 micrograms/ml, RU44790 inhibited 90% of all strains of the family Enterobacteriaceae with the exception of Citrobacter spp. (MIC for 90% of strains tested, 1.2 micrograms/ml). The activity was similar to that of aztreonam against strains that are normally susceptible to expanded-spectrum cephalosporins. On the other hand, the new compound was 10 to 100 times more potent than aztreonam and most of the other antibiotics tested against enterobacteria that produce chromosome-encoded or plasmid-mediated extended-spectrum beta-lactamases. Pseudomonas aeruginosa isolates were equally susceptible to both monobactams. RU44790 was inactive against staphylococci and had only marginal activity against streptococci (MIC for 50% of strains tested, 2.5 micrograms/ml). RU44790 was highly resistant to hydrolysis by various beta-lactamases, particularly cephalosporinases such as P99. The latter enzyme was also inhibited by the compound. RU44790 showed a high affinity for penicillin-binding protein 3 of Escherichia coli. The results suggest that RU44790 has good potential in the treatment of infections caused by gram-negative microorganisms. PMID- 1416859 TI - Inhibition of rabies virus transcription in rat cortical neurons with the dissociative anesthetic ketamine. AB - In a previous study (B. P. Lockhart, H. Tsiang, P. E. Ceccaldi, and S. Guillemer, Antiviral Chem. Chemother. 2:9-15, 1991), we demonstrated an antiviral effect of the general anesthetic ketamine for rabies virus in neuronal cultures and in rat brain. This report describes an attempt to determine at what level ketamine acts on the rabies virus cycle in rat cortical neuron cultures. Immunofluorescence and [35S]methionine labelling of infected neurons showed that ketamine (1 to 1.5 mM) inhibited viral nucleoprotein and glycoprotein syntheses. Northern (RNA) blots of total RNA from drug-treated neurons, hybridized with 32P-labelled oligonucleotide probes for rabies virus nucleoprotein, matrix protein, and glycoprotein genes, showed a marked reduction (5- to 11-fold) in the levels of rabies virus mRNAs, relative to those in untreated neurons. No significant change in the levels of cellular beta-actin mRNA were detected in ketamine-treated cells. A similar antiviral effect was observed with MK-801; however, no inhibition of rabies virus synthesis was observed with the general anesthetic chloral hydrate. The antiviral effect was not complete; a time-dependent recovery of viral transcription and rabies virus protein synthesis was observed, but no infectious virus was released into the culture supernatant. The lack of any modification of cellular protein or mRNA synthesis by ketamine suggests an antiviral mechanism acting at the level of rabies virus genome transcription. PMID- 1416861 TI - Orally administered cefpodoxime proxetil for treatment of uncomplicated gonococcal urethritis in males: a dose-response study. AB - An open-label, dose-response study of cefpodoxime proxetil (CPD), an expanded spectrum cephalosporin, was conducted with 58 males with uncomplicated Neisseria gonorrhoeae infections with single doses of 600, 400, 200, 100, or 50 mg of CPD administered orally by tablet. CPD eradicated N. gonorrhoeae in all 50 evaluable patients (10 per group) at all doses studied. Eight of the isolates eradicated were beta-lactamase-producing organisms. Two patients reported three side effects, nausea, vomiting, and diarrhea, which were mild and resolved without intervention or sequelae. There were no clinically remarkable drug-related changes in vital signs or clinical laboratory assays. Results show that single oral doses of CPD are an effective and well-tolerated treatment for uncomplicated N. gonorrhoeae infection in males at doses as low as 50 mg. PMID- 1416862 TI - Analysis of vancomycin time-kill studies with Staphylococcus species by using a curve stripping program to describe the relationship between concentration and pharmacodynamic response. AB - Mono- and biexponential killing curves for vancomycin over a 2- to 50 micrograms/ml concentration range were generated for 11 Staphylococcus aureus isolates and 12 coagulase-negative Staphylococcus species in the logarithmic phase of growth. Nonlinear least-squares regression of the initial growth rate and disappearance were not significantly different for lower or higher concentrations of vancomycin in broth. PMID- 1416863 TI - Long-term tolerance and efficacy of 3'-azidothymidine and 3'-fluorothymidine treatment of asymptomatic monkeys infected with simian immunodeficiency virus. AB - Macaques chronically infected with simian immunodeficiency virus were treated with zidovudine (20 mg/kg of body weight per day for 9 weeks) or 3' fluorothymidine (5 mg/kg of body weight per day for 9 weeks or three doses of 2 mg/kg per day for 24 days). Hematological changes in the treated animals included macrocytic anemia and leukopenia. Determination of antiviral effects in this model requires improved assay methods. PMID- 1416864 TI - Pharmacokinetics of concomitantly administered foscarnet and zidovudine for treatment of human immunodeficiency virus infection (AIDS Clinical Trials Group protocol 053). AB - Foscarnet and zidovudine (ZDV) pharmacokinetic parameters were not altered in five patients receiving 14 days of concomitant therapy. Foscarnet clearance in plasma averaged (+/- standard deviation) 0.16 +/- 0.03 and 0.13 +/- 0.05 liter/h/kg of body weight in the absence and presence of ZDV. ZDV parameters were also not significantly altered, with a mean (+/- standard deviation) oral clearance of 2.7 +/- 1.0 and 2.6 +/- 0.8 liter/h/kg for the 2 study days, respectively. PMID- 1416866 TI - Increased susceptibility of transfected prokaryotic and eukaryotic cells to antibiotic selection. AB - At 39 to 40 degrees C, selection of antibiotic-resistant transfected mammalian cell lines or Escherichia coli required lower aminoglycoside antibiotic concentrations than at 37 degrees C. The thermosensitivity of antibiotic susceptibility was much more manifest during genetic selection experiments than in conventional growth inhibition assays. PMID- 1416865 TI - Effects of squalene epoxidase inhibitors on Candida albicans. AB - The relationship between sterol biosynthesis inhibition, membrane integrity, and cell growth inhibition in Candida albicans was examined for five squalene epoxidase inhibitors. The compounds were the thiocarbamates tolnaftate and tolciclate and the allylamines naftifine, terbinafine, and SDZ 87-469. All compounds inhibited sterol biosynthesis, with the concentrations that caused a 50% decrease in the total sterol-to-squalene ratio ranging from less than or equal to 0.01 microM for terbinafine and SDZ 87-469 to 500 microM for tolnaftate. At 100 microM, the compounds also caused up to a 30% release of intracellular [14C]aminoisobutyric acid. With terbinafine and SD2 87-469, aminoisobutyric acid release further increased in cells grown at concentrations that inhibited ergosterol biosynthesis. It is suggested that inhibition of ergosterol synthesis may render the C. albicans membrane susceptible to further damage, including direct damage from squalene epoxidase inhibitors. PMID- 1416867 TI - In vitro activities of streptomycin and 11 oral antimicrobial agents against clinical isolates of Klebsiella rhinoscleromatis. AB - We tested in vitro the activities of streptomycin and tetracycline--antibiotics that have long been used to treat rhinoscleroma--as well as several newer oral agents by using 23 isolates of the causative organism Klebsiella rhinoscleromatis. All isolates were inhibited by clinically achievable concentrations of trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, chloramphenicol, ciprofloxacin, cephalexin, cefuroxime, and cefpodoxime. PMID- 1416868 TI - In vitro susceptibilities of Borrelia burgdorferi to five oral cephalosporins and ceftriaxone. AB - We determined the in vitro susceptibilities of eight Borrelia burgdorferi isolates to five oral cephalosporins. MICs for B. burgdorferi 297 were 23 micrograms/ml (cephalexin), 45 micrograms/ml (cefadroxil), 91 micrograms/ml (cefaclor), 0.13 microgram/ml (cefuroxime), 0.8 microgram/ml (cefixime), and 0.02 microgram/ml (ceftriaxone). When B. burgdorferi isolates were exposed to concentrations twice the MIC of cefuroxime, cefixime, or ceftriaxone, at least 72 h of incubation was required to kill 99% of the organisms. PMID- 1416869 TI - Susceptibilities of ampicillin-resistant strains of Salmonella other than S. typhi to 10 antimicrobial agents. AB - Ampicillin-resistant strains of Salmonella other than S. typhi constitute a health problem. We tested the antimicrobial susceptibilities to 10 antibiotics of 57 of these strains isolated in a 30-month period. The rates of resistance were as follows: chloramphenicol, 40.3%; tetracycline, 33.3%; gentamicin, 5.3%; co trimoxazole, 5.3%; nalidixic acid, 1.8%; and amoxicillin-clavulanic acid, cefotaxime, ceftriaxone, aztreonam, and ciprofloxacin, 0%. In our experience, there are alternative antibiotics with excellent in vitro activities. PMID- 1416870 TI - In vitro models for studying toxicity of antifungal agents. PMID- 1416871 TI - Standardized susceptibility testing of fluconazole: an international collaborative study. AB - An international collaborative study of broth dilution (MIC) and disk diffusion susceptibility testing of fluconazole was conducted by using a chemically defined medium (High-Resolution Antifungal Assay Medium; Oxoid Ltd., Basingstoke, United Kingdom) and standard test methods performed in eight reference laboratories. Ten yeast isolates were tested by each test method in duplicate on each of 3 separate days. The intralaboratory reproducibility of the MIC test was excellent; 95.7% of the replicate tests (n = 220) were within 2 doubling dilutions of the other values in the set for the eight laboratories. The intralaboratory reproducibility of the disk test was also good, with 91% of the replicate tests (n = 234) agreeing with each other within an arbitrarily chosen value of 4 mm. Interlaboratory agreement of MIC test results was acceptable, with 84% of the MICs agreeing within 2 doubling dilutions. In contrast, the interlaboratory agreement of the disk test was not good, with only 59% of test results agreeing within 4 mm. Comparison of the rank order of MICs obtained in each laboratory with the reference rank order gave an agreement of 70 to 80% (median, 80%) with the MIC test and 70 to 90% (median, 80%) with the disk test. These preliminary results are encouraging for the development of standardized testing methods for testing fluconazole. PMID- 1416872 TI - Prediction of human pharmacokinetics of panipenem-betamipron, a new carbapenem, from animal data. AB - The pharmacokinetic behavior of panipenem (PAPM)-betamipron (BP), a new carbapenem, in humans was successfully predicted from data collected from six animal species. PAPM and BP were biphasically eliminated from plasma after intravenous (i.v.) administration of PAPM-BP to mice, guinea pigs, rats, rabbits, monkeys, and dogs. Elimination rates of PAPM and BP were correlated with animal size: the larger the animal was, the slower the elimination was. As for PAPM and BP, log-log plots of total plasma clearance (CLtot) versus body weight and log log plots of distribution volume at steady state (VSS) versus body weight for six animal species were linear, with high correlation coefficients. These allometric equations were extrapolated to predict CLtot and VSS for PAPM and BP in humans. In addition, concentration in plasma-time profiles for humans were predicted by using two-exponent equations fitted to the complex Dedrick plot of animal data. Predicted values for CLtot and VSS for PAPM and BP in humans agreed well with observed values in humans given 750/750 mg of PAPM-BP as an i.v. drip infusion for 30 min. Predicted concentration in plasma-time profiles for humans approximated observed profiles. Thus, the pharmacokinetics of PAPM-BP extrapolated well from animal species to humans when allometric equations and the complex Dedrick plot were used. PMID- 1416873 TI - Nucleotide sequences of CAZ-2, CAZ-6, and CAZ-7 beta-lactamase genes. AB - CAZ-2, CAZ-6, and CAZ-7 are plasmid-mediated beta-lactamases that are markedly active against ceftazidime. The corresponding structural genes were amplified by the polymerase chain reaction. Nucleotide sequences were determined by direct sequencing of the amplified products. Analysis of the nucleotide and the deduced amino acid sequences showed that CAZ-2, CAZ-6, and CAZ-7 are derived from TEM-2 by three, four, and two amino acid substitutions, respectively. All these substitutions are located at positions 102, 162, 235, 236, and 237 (Sutcliffe numbering), which are known to extend the substrate range of beta-lactamases. These substitutions are Lys-102, Ser-162, and Ser-236 in CAZ-2; Lys-102, Ser-162, Thr-235, and Lys-237 in CAZ-6; and Lys-102 and His-162 in CAZ-7. These results indicate that the nucleotide sequence of CAZ-2 is identical to that of TEM-8. The nucleotide sequence of CAZ-7 possesses the two mutations described in TEM-16 by the oligotyping method. In contrast, the combination of mutations encountered in CAZ-6 has not yet been described, and this enzyme was designated TEM-24. PMID- 1416874 TI - Primary and secondary metabolism of pentamidine by rats. AB - The antiprotozoal drug pentamidine [1,5-bis(4'-amidinophenoxy)pentane] has been previously shown to be metabolized by rat liver microsomes, and five of the seven putative primary metabolites have been identified. With the synthesis and identification of 5-(4'-amidinophenoxy)pentanoic acid and 5-(4'-amidinophenoxy)-1 pentanol as the remaining two metabolites, the primary metabolism of pentamidine in rats appears fully characterized. Use of [14C]pentamidine with rat liver microsomes confirms this conclusion, since no unidentified radioactive peaks were detected by high-performance liquid chromatography (HPLC). Isolated, perfused rat livers were used with [14C]pentamidine to identify secondary metabolites. Only two novel radioactive peaks were detected by HPLC analysis of perfused liver samples. The treatment of liver samples with sulfatase or beta-glucuronidase resulted in the reduction or elimination of these peaks and gave rise to peaks identified as para-hydroxybenzamidine and 5-(4'-amidinophenoxy)pentanoic acid. It was concluded from these results that only these two primary metabolites were conjugated with sulfate or glucuronic acid. After 4 h of incubation in the perfused liver system, approximately 15% of the recovered radiolabel was pentamidine. These results suggest that pentamidine metabolism can be rapid and extensive in rats. PMID- 1416875 TI - Effect of concomitant administration of piperacillin on the dispositions of isepamicin and gentamicin in patients with end-stage renal disease. AB - Piperacillin inactivation of the aminoglycosides isepamicin and gentamicin in 12 chronic hemodialysis patients was assessed. Six subjects each received isepamicin (7.5 mg/kg of body weight) or gentamicin (2 mg/kg) alone and in combination with piperacillin (4 g every 12 h for four doses). Isepamicin and gentamicin concentrations in plasma and urine were monitored over 48 h after each dose and analyzed by high-performance liquid chromatography and fluorescence polarization immunoassay, respectively. The pharmacokinetics of isepamicin were not significantly altered during combination treatment with piperacillin. The total body clearance (3.79 +/- 0.71 versus 3.94 +/- 1.05 ml/min), the steady-state volume of distribution (0.19 +/- 0.04 versus 0.18 +/- 0.03 liter/kg), and the terminal elimination half-life (47.91 +/- 7.20 versus 45.08 +/- 10.34 h) were not significantly altered in the presence of piperacillin. In contrast, the terminal elimination half-life (47.68 +/- 20.58 versus 35.67 +/- 11.18 h) of gentamicin was significantly reduced when gentamicin was given with piperacillin. The total body clearance (4.26 +/- 3.07 versus 4.89 +/- 1.94 ml/min) and the steady-state volume of distribution (0.19 +/- 0.04 versus 0.20 +/- 0.04 liter/kg) of gentamicin were not significantly altered during combination therapy; however, the nonrenal clearance of gentamicin administered in combination with piperacillin (3.56 +/- 0.38 ml/min) increased significantly compared with that of gentamicin (2.03 +/- 0.50 ml/min) given alone. The results of this study suggest that no additional dosage adjustment of isepamicin during concomitant therapy with piperacillin in hemodialysis patients is necessary. However, this does not preclude the need for appropriately ex vivo-handled specimens for monitoring isepamicin concentrations in plasma to ensure therapeutic efficacy and prevent toxicity. Furthermore, additional dosage adjustments may be necessary when gentamicin is used concomitantly with piperacillin, on the basis of the significant in vivo inactivation that takes place in end-stage renal disease patients. PMID- 1416876 TI - Cross-resistance to meropenem, cephems, and quinolones in Pseudomonas aeruginosa. AB - Multiple-drug-resistant mutants were isolated from Pseudomonas aeruginosa PAO1 on agar plates containing ofloxacin and cefsulodin. These mutants were four to eight times more resistant to meropenem, cephems, carbenicillin, quinolones, tetracycline, and chloramphenicol than the parent strain was. In contrast, these mutants showed no significant changes in their susceptibilities to all carbapenems except meropenem. In these mutants, the amounts of an outer membrane protein with an apparent molecular weight of 49,000 (designated OprM) were increased compared with the amount in PAO1. Multiple-drug-resistant mutants of this type were also isolated from PAO1 on agar plates containing meropenem. Approximately 5% of clinical isolates showed cross-resistance to meropenem, cephems, and quinolones, concomitant with overproduction of OprM. Moreover, these two phenotypes, i.e., multiple-drug resistance and overproduction of OprM, were cotransferable by transduction. These data suggest that overproduction of OprM is associated with cross-resistance to meropenem, cephems, and quinolones in P. aeruginosa. The ofloxacin-cefsulodin-resistant mutant required higher concentrations of meropenem to induce beta-lactamase than PAO1 did, indicating the possibility that this mutation involves decreased outer membrane permeability to meropenem. PMID- 1416877 TI - Liquid chromatographic determination of amoxicillin concentrations in bovine plasma by using a tandem solid-phase extraction method. AB - We report a means of determining amoxicillin in bovine plasma by liquid chromatography with UV detection at 235 nm. Purification and concentration of extracts were accomplished by a tandem solid-phase extraction procedure with two reversed-phase columns. Separation of amoxicillin from interferences was improved by the incorporation of a crown ether in the solvent systems used both for the solid-phase extraction and the final high-pressure liquid chromatography. Cefadroxil was added as an internal standard. The average recovery of amoxicillin from plasma (n = 23) was 78.2 +/- 3.0%, and the within-run and between-run coefficients of variation ranged from 1.8 to 7.0%. The detection limit was estimated at 0.1 microgram/ml. This method was used to determine amoxicillin in bovine plasma after intramuscular administration of the drug. PMID- 1416878 TI - Detection of extended-spectrum beta-lactamases in members of the family Enterobacteriaceae: comparison of the double-disk and three-dimensional tests. AB - The three-dimensional and clavulanate double-disk potentiation tests were compared as procedures for the detection of extended-spectrum beta-lactamase production in 32 strains of Escherichia coli and Klebsiella pneumoniae, 31 of which produced TEM-1, TEM-2, TEM-3, TEM-4, TEM-5, TEM-7, TEM-8, TEM-9, TEM-10, TEM-12, TEM-101, SHV-1, SHV-2, SHV-3, SHV-4, SHV-5, CAZ-2, MIR-1, or an unidentified extended-spectrum beta-lactamase with a pI of 5.95, with some strains producing multiple beta-lactamases. The three-dimensional test, which was performed in conjunction with a routine disk diffusion test, detected extended spectrum beta-lactamase production in 26 of 28 (93%) of the strains that produced extended-spectrum beta-lactamases. The clavulanate double-disk potentiation test detected extended-spectrum beta-lactamases in only 22 of the 28 strains (79%) when it was performed as currently recommended. The three-dimensional test, when performed in conjunction with the disk diffusion test, offered the advantages of providing simultaneous information about both antibiotic susceptibility and extended-spectrum beta-lactamase production, coupled with a greater sensitivity and earlier detection of extended-spectrum beta-lactamases. PMID- 1416879 TI - In vitro and in vivo antibacterial activities of E1077, a novel parenteral cephalosporin with a broad antibacterial spectrum. AB - E1077 is a new injectable cephalosporin with a broad spectrum of antibacterial activity against gram-positive and gram-negative bacteria, including staphylococci and Pseudomonas aeruginosa. The in vitro activities of E1077 against clinical isolates of methicillin-susceptible Staphylococcus aureus (MIC of E1077 for 90% of the strains tested [MIC90], 0.78 microgram/ml) and methicillin-resistant S. aureus (MIC90, 50 micrograms/ml) were similar to those of cefpirome and flomoxef. Against Enterococcus faecalis (MIC90, 6.25 micrograms/ml), E1077 was the most active of the drugs tested and four times more active than cefpirome. The MIC90S of E1077 for streptococci, Haemophilus influenzae, and Neisseria gonorrhoeae ranged from 0.05 to 0.78 microgram/ml; E1077 was similar in activity to cefpirome. E1077 inhibited 90% of most species of the family Enterobacteriaceae at concentrations of less than or equal to 1.56 micrograms/ml, with the exception of Serratia marcescens and Proteus vulgaris (12.5 micrograms/ml). The activity of E1077 against P. aeruginosa (MIC90, 6.25 micrograms/ml) was comparable to that of ceftazidime. In vivo activity was evaluated with systemic infections in mice. E1077 showed a protective effect against systemic infections by gram-positive or gram-negative bacteria, as reflected by its in vitro activity. The protective effects of E1077 were higher than those of cefpirome against S. aureus and P. aeruginosa infections and similar to those of cefpirome against other bacterial infections. Morphological studies using differential interference and phase-contrast microscopy showed that low concentrations of E1077 caused swelling of S. aureus and spheroplast and bulge formation in P. aeruginosa. In general, the antibacterial profile of E1077 is similar to that of cefpirome. PMID- 1416880 TI - Diffusion of meropenem and imipenem through the outer membrane of Escherichia coli K-12 and correlation with their antibacterial activities. AB - The outer membrane permeability to meropenem and imipenem in Escherichia coli K 12 was investigated, and its porin-deficient mutants were transformed with a constructed vector carrying the carbapenem-hydrolyzing CphA metallo-beta lactamase gene. By using the method of Zimmermann and Rosselet, meropenem was shown to penetrate through the outer membrane of E. coli K-12 five times faster than cephaloridine but twice as slowly as imipenem. Lack of one or both porins significantly reduced the penetration of both carbapenems. No evidence of specific porin pathways of the type described in Pseudomonas aeruginosa was found. Despite its slower penetration, meropenem was two to eight times more active than imipenem against both parent and porin-defective mutants, whether harbouring CphA beta-lactamase or not. Meropenem was also more active than imipenem against E. coli DC2, a strain with a breakdown in the outer membrane permeability which made periplasmic concentrations of beta-lactams similar to the external concentrations. In this strain, meropenem caused a more than 50% reduction in cell number increase at a concentration very close to the 50% inhibitory concentration for penicillin-binding protein type 2 (PBP 2), whereas imipenem, at the same concentration, did not significantly inhibit cell growth. This result was explained by the higher affinity of meropenem for PBP 3 compared with imipenem and supports the conclusion that synergistic inhibition of both PBPs was the main mechanism in the better antibacterial activity of meropenem. PMID- 1416881 TI - Chitin biosynthesis in Candida albicans grown in vitro and in vivo and its inhibition by nikkomycin Z. AB - An N-acetyl-D-[14C]glucosamine radiolabel incorporation assay has been used to monitor chitin biosynthesis in whole cells of Candida albicans both in vitro and in vivo in two different mouse infection models, one using the peritoneal cavity as a chamber in which to add and retrieve cells and the other using infected kidneys. Specific labeling of chitin in alkali-insoluble material was confirmed by chitinase digestion, analysis of acid hydrolysates, and the use of nikkomycin Z as a probe. Nikkomycin Z was shown to strongly inhibit chitin biosynthesis in C. albicans grown in vitro and in vivo in both models. This demonstrates that nikkomycin Z-susceptible chitin synthase activity is present in C. albicans when the fungus is in its pathogenic state in vivo. The limited use of nikkomycin as a therapeutic agent is discussed. PMID- 1416882 TI - Potential effects of erythromycin on host defense systems and virulence of Pseudomonas aeruginosa. AB - We evaluated several potential effects of erythromycin (EM) on host defense systems and the virulence of Pseudomonas aeruginosa. Peritoneal macrophages obtained from mice given 250 mg of EM per kg of body weight for 7 days by the intraperitoneal, intravenous, subcutaneous, or oral route produced significantly greater amounts of thymocyte-activating factors. These data suggest that EM enhances the in vivo production of cytokines, such as interleukins 1 and 6. Treatment of P. aeruginosa D4 with subinhibitory concentrations of EM enhanced the association of bacteria with murine Kupffer cells in vitro and increased bacterial clearance from the blood in mice. EM suppressed the in vitro production of exotoxin A, total protease, elastase, and phospholipase C by P. aeruginosa D4; exotoxin A production by P. aeruginosa PA-103; and total protease production by P. aeruginosa B16 and PAO1 in a generally dose-dependent manner. These data demonstrate that EM produces various effects in addition to its direct antimicrobial activity, suggesting that it has potential as an immunomodulator or bacterial virulence-suppressing agent against P. aeruginosa and other infections. PMID- 1416883 TI - In vitro activity of L-627, a new carbapenem. AB - The in vitro activity of L-627, a new parenterally administered carbapenem, was compared with those of imipenem, meropenem, FCE 22101 (a penem), ceftazidime, and ceftriaxone. L-627 was active against members of the family Enterobacteriaceae (MIC for 90% of strains tested [MIC90] ranging from 0.03 to 4 micrograms/ml). L 627 displayed activity equal to that of meropenem against Pseudomonas aeruginosa (MIC90, 2 micrograms/ml), although, as with other carbapenems, the antipseudomonal activity was reduced against D2-deficient strains. Staphylococci and streptococci were susceptible (MIC90 of 1.0 micrograms/ml for Staphylococcus aureus and 0.015 micrograms/ml for group A streptococci). L-627 also had activity against anaerobic bacteria (MIC90, 2.0 micrograms/ml for Bacteroides fragilis). Neisseria gonorrhoeae and Neisseria meningitidis were highly susceptible (MIC90, 0.06 micrograms/ml), and against the common respiratory pathogens (Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis), the MIC90s were less than or equal to 2.0 micrograms/ml. The protein binding of L-627 ranged from 13.8 to 22%, depending on the concentration. The presence of human serum had little effect on the MIC or MBC of L-627. These results suggest that L-627 merits further study in the treatment of infections caused by a wide range of pathogens. PMID- 1416884 TI - Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia. AB - The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of greater than or equal to 60 mg/kg/day was highly effective in treatment and prophylaxis. Low (less than or equal to 15 mg/kg/day) doses of SMX showed limited, dose-related anti-Pneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, demonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides and suggested that further exploration of this class of compounds might lead to clinically useful agents. PMID- 1416886 TI - Adaptive resistance following single doses of gentamicin in a dynamic in vitro model. AB - Adaptive resistance is a phenomenon recently described for Pseudomonas aeruginosa and other gram-negative bacilli following exposure to aminoglycoside antibiotics. It is a reversible form of resistance which develops within 1 to 2 h of initial exposure to an aminoglycoside and disappears several hours after removal of the antibiotic. We investigated adaptive resistance in P. aeruginosa ATCC 27853 following single doses of gentamicin by using a dynamic in vitro model which mimics in vivo pharmacokinetics. The initial peak gentamicin concentrations were 2.5, 8, and 25 mg/liter, and these were followed by an exponential decay in the concentration, with a half-life of 2.5 h. The degree of adaptive resistance was greater and the duration was longer with higher initial gentamicin concentrations. Maximal adaptive resistance occurred between 2 and 10 h following 8 mg/liter and between 2 and 16 h following 25 mg/liter. Full recovery of susceptibility occurred at approximately 36, 39, and 43 h following 2.5, 8, and 25 mg/liter, respectively, at which times the gentamicin concentrations were extremely low. Longer dosing intervals for aminoglycosides may improve efficacy by allowing time for adaptive resistance to resolve. PMID- 1416885 TI - Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs. AB - Over a 7-year period, we analyzed 261 dose regimens of antimicrobial drugs in the treatment and prevention of Pneumocystis carinii pneumonia in an immunosuppressed rat model. These compounds ranged from drugs in clinical use to newly synthesized agents. Drug efficacy was expressed as the magnitude of the reduction in median P. carinii cyst or nucleus counts on a scale ranging from inactive (less than 5 fold) to very markedly active (greater than or equal to 1,000-fold). The classification system was reproducible and allowed drugs studied at different times to be compared with each other. The system demonstrated a hierarchy of anti P. carinii activity not only among classes of compounds but also among individual members of a drug class. Sulfonamides, sulfones, and diamidines were the most active agents; some purine nucleosides and nitrofurans also showed promising activity; and most antiparasitic, antifungal, antibacterial, and antiviral drugs were inactive. We conclude that this classification system represents a simple, quantitative method of comparing the activities of antimicrobial drugs against P. carinii. Information gained from this system should be helpful in developing new anti-P. carinii compounds and establishing standard procedures for their evaluation. PMID- 1416887 TI - Pharmacokinetics of [14C]FCE 22891, a penem antibiotic, following oral administration to healthy volunteers. AB - FCE 22891 is a prodrug of the penem antibiotic FCE 22101 and is suitable for oral administration. The pharmacokinetics of FCE 22891 were investigated in four healthy male volunteers following the oral administration of 500 mg of [14C]FCE 22891. Levels of radioactivity in plasma were always higher and persisted for longer than those of FCE 22101. The time to the maximum concentration of radioactivity in plasma generally coincided with that of FCE 22101. The respective values for the maximum concentrations of radioactivity in plasma were, on average, 8.57 +/- 2.95 micrograms equivalent/ml and 2.97 +/- 2.05 micrograms/ml. Over a 5-day period, mean urinary and fecal recovery of radioactivity accounted for 53.2 and 41.0% of the dose, respectively. The average amount of FCE 22101 excreted in urine and feces corresponded to 9.0 and 1.6% of the dose, respectively. The urinary recovery of the open-ring metabolite P1 and of its 5-S epimer P2 accounted for about 6.5 and 1.2% of the dose, respectively. Other chromatographic peaks corresponding to nonidentified compounds accounted for about 14.0% (polar metabolite fraction; peak P), 3.7% (less polar fraction; peak X), and 15.4% (least polar fraction) of the dose. Elimination of radioactivity and FCE 22101 in urine was rapid. Intersubject variability in the kinetics of total radioactivity in plasma was far less than that observed for FCE 22101. The results of the present study support suggestions that presystemic metabolism of FCE 22101 and/or transformation of the prodrug to compounds other than FCE 22101 are the main cause of intersubject variability in the kinetics of FCE 22101 produced in plasma following oral administration of its prodrug. PMID- 1416888 TI - Antipneumocystis activity of water-soluble lipopeptide L-693,989 in rats. AB - Water-soluble lipopeptide L-693,989 was evaluated for its antipneumocystis activity in rats. Rats from colonies with latent Pneumocystis carinii infections were immunosuppressed with dexamethasone for 6 weeks to facilitate the development of acute P. carinii pneumonia (PCP). After 6 weeks, the rats were maintained on dexamethasone and were treated twice daily for 4 days with various concentrations of L-693,989. At a dose of 0.15 mg/kg of body weight, the compound effectively eliminated 90% of the cysts in 4 days. Trophozoite forms of P. carinii were still present in these animals, as determined by using a P. carinii specific DNA probe. A 3-week therapy study showed that the trophozoite load did not expand during treatment and that the trophozoites already present at the initiation of therapy appeared to persist. This may be a consequence of the stage specificity of the compound for cyst development and the severe immunosuppressive effects of dexamethasone on rats. When evaluated as a daily parenteral prophylactic agent, L-693,989 was effective in preventing the development of both P. carinii cysts and trophozoites, demonstrating its potential for use in prophylaxis and implying that the cyst stage of P. carinii is an obligatory step in trophozoite multiplication. The foamy exudate commonly associated with P. carinii infections was absent in the lungs of rats on prophylaxis. The compound was also evaluated via oral administration and was found to have a 90% effective dose of 32 mg/kg for therapy of acute infections and 5 mg/kg for daily prophylaxis. PMID- 1416890 TI - Activity of amphotericin B cholesterol dispersion (Amphocil) in experimental visceral leishmaniasis. AB - Standard therapy of human visceral leishmaniasis with parenteral pentavalent antimonial agents is generally curative but has the disadvantages of a 28-day treatment course, occasional treatment failures, and toxicity. The antifungal and antileishmanial agent amphotericin B has been complexed with lipids to develop a less toxic formulation of amphotericin B. Because lipid particles are phagocytized by the reticuloendothelial system, lipid-associated amphotericin B should be concentrated in infected macrophages and be very effective against visceral leishmaniasis. One formulation, amphotericin B cholesterol dispersion (ABCD) (Amphocil), was tested for antileishmanial activity in Leishmania donovani infected hamsters. In the first experiment, hamsters were infected, administered with the drug 3 days later, and then sacrificed after a further 4 days. ABCD (dose needed to suppress 99% of hepatic parasites compared with controls [SD (99)], 0.4 mg/kg of body weight) was 15 times as effective as conventional amphotericin B [SD (99), 6.0 mg/kg]. Pentavalent antimony in the form of meglumine antimonate had an SD (84) of 416 mg/kg. In a second experiment in which animals were allowed to become more heavily infected, the drug was administered 10 days after infection and the animals were sacrificed after a further 2, 7, or 11 days. ABCD was approximately four times as active as conventional amphotericin B. These experiments suggest that ABCD is at least four times as active as conventional amphotericin B against visceral leishmaniasis and that clinical trials are warranted. PMID- 1416889 TI - Studies of the effect of a platelet-activating factor antagonist, CL 184,005, in animal models of gram-negative bacterial sepsis. AB - The effect of CL 184,005, a potent and specific platelet-activating factor antagonist, has been examined in a variety of animal models relevant to gram negative bacterial sepsis. Pretreatment of mice with CL 184,005 protected them from the lethal effects of platelet-activating factor. When rats or primates rendered hypotensive with endotoxin were treated with CL 184,005, blood pressure was normalized. Pretreatment of rats with CL 184,005 protected them from the gastrointestinal lesions induced by endotoxin. Pretreatment of rats and mice with CL 184,005 protected them from the lethal effects of endotoxin. Plasma tumor necrosis factor levels in endotoxin-treated mice were lower when the mice were pretreated with CL 184,005. These observations suggest that CL 184,005 may be potentially useful in the treatment of gram-negative bacterial sepsis, and the agent is undergoing clinical evaluation. PMID- 1416891 TI - Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system. AB - MICs of clarithromycin against 324 clinical isolates belonging to eight species of slowly growing nontuberculous mycobacteria were determined by using a broth microdilution system. Isolates were inoculated into twofold drug dilutions in Middlebrook 7H9 broth (pH corrected to 7.4) and then incubated at 30 degrees C for 7 days for Mycobacterium marinum and for 14 days for all other species. The MIC for 90% of the strains (MIC90) was less than or equal to 0.5 micrograms/ml for isolates of Mycobacterium gordonae (6 strains), Mycobacterium scrofulaceum (5 strains), Mycobacterium szulgai (6 strains), and Mycobacterium kansasii (35 strains). MICs for M. marinum (25 strains) and Mycobacterium avium complex (237 strains) were higher, but 100% and 89% of the strains, respectively, were susceptible to less than or equal to 4 micrograms/ml. In contrast, MICs for five of six M. simiae strains were greater than 8 micrograms/ml, and the range of MICs for Mycobacterium nonchromogenicum varied from less than or equal to 0.125 to 8 micrograms/ml. For the 237 isolates of M. avium complex, the MIC50 was 2 micrograms/ml and the MIC90 was 8 micrograms/ml. MICs for most isolates (77%) were in the 1- to 4-micrograms/ml range. For the 80 isolates in this group known to be from AIDS patients, the MIC50 was 4 micrograms/ml and the MIC90 was 8 micrograms/ml. These MIC studies combined with preliminary clinical trials suggest that clarithromycin may be useful for drug therapy of most species of the slowly growing nontuberculous mycobacteria except M. simiae. PMID- 1416892 TI - Outbreak of ceftazidime resistance due to a novel extended-spectrum beta lactamase in isolates from cancer patients. AB - Ceftazidime is widely used in the therapy of infectious complications in neutropenic patients. We studied an outbreak of ceftazidime-resistant gram negative bacillary infections in pediatric cancer patients receiving empirical ceftazidime therapy for neutropenic fever. Fourteen isolates (12 Klebsiella pneumoniae and 2 Escherichia coli) from 13 patients were studied. Specimens were obtained from multiple clinical sites including blood, urine, throat, and lung. The organisms were resistant to ceftazidime, aztreonam, and penicillins but remained susceptible to cephamycins and imipenem. All resistant isolates produced a novel beta-lactamase (TEM-26) with a pI of approximately 5.58, which was transferred by transformation to E. coli on a 7.9-kb nonconjugative plasmid which cotransferred resistance to trimethoprim-sulfamethoxazole. This enzyme readily hydrolyzed ceftazidime, aztreonam, and penicillins in a spectrophotometric assay. DNA sequencing data suggest that TEM-26 is derived from TEM-1. PMID- 1416893 TI - Vancomycin resistance gene vanC is specific to Enterococcus gallinarum. AB - Nearly all strains of Enterococcus gallinarum are resistant to low levels of vancomycin. The glycopeptide resistance gene vanC from E. gallinarum BM4174 has recently been cloned and sequenced. A probe specific for vanC hybridized with a 2.7-kb EcoRI and a 4.5-kb HindIII fragment of total DNA from the 42 strains of E. gallinarum studied. No homology was detected with DNA of strains belonging to other species intrinsically resistant to vancomycin, including Enterococcus casseliflavus, a species that expresses a vancomycin resistance phenotype similar to that of E. gallinarum. No hybridization with DNA of enterococcal strains with acquired resistance to high or low levels of vancomycin was observed. The specificity of the vanC probe allowed us to distinguish E. gallinarum from 12 other species of enterococci, indicating that this probe is a useful tool for species identification within the genus Enterococcus. PMID- 1416894 TI - Presence of Clostridium difficile and antibiotic and beta-lactamase activities in feces of volunteers treated with oral cefixime, oral cefpodoxime proxetil, or placebo. AB - Three groups of six healthy adult volunteers were randomly assigned to a treatment with 400 mg of oral cefpodoxime proxetil, oral cefixime, or placebo per day for 10 days. Informed consent was obtained from all volunteers. Clostridium difficile was not detected in the feces of any subject before treatment or at any time in the subjects in the placebo group. C. difficile was, however, detected in all subjects treated with cefpodoxime proxetil and in five of six treated with cefixime. Genomic DNA restriction patterns showed that the strains of C. difficile differed from one volunteer to another. Two subjects both shed different strains at different times during the 25-day surveillance period. All isolates were resistant to cefixime and cefpodoxime (MIC for 90% of strains, 256 and 512 mg/liter, respectively). Antibiotic activity was found in the feces of one volunteer treated with cefpodoxime proxetil and of four volunteers treated with cefixime. It was inversely correlated with the presence of fecal beta lactamase activity. Intestinal side effects were limited to modifications of stool consistency, which occurred in only 3 of the 12 treated volunteers and did not lead to cessation of treatment. These modifications were significantly associated with the presence of fecal antibiotic activity (P less than 0.05) but not with the shedding of toxigenic or nontoxigenic strains of C. difficile or with the presence of toxin A in feces, which was detected only in one perfectly healthy treated volunteer. PMID- 1416895 TI - Antimicrobial prophylaxis for major head and neck surgery in cancer patients: sulbactam-ampicillin versus clindamycin-amikacin. AB - A total of 99 patients with head and neck cancer who were to undergo surgery were randomized in a prospective comparative study of sulbactam-ampicillin (1:2 ratio; four doses of 3 g of ampicillin and 1.5 g of sulbactam intravenously [i.v.] every 6 h) versus clindamycin (four doses of 600 mg i.v. every 6 h)-amikacin (two doses of 500 mg i.v. every 12 h) as prophylaxis starting at the induction of anesthesia. The two groups of evaluable patients (43 in the clindamycin-amikacin treatment group and 42 in the sulbactam-ampicillin treatment group) were comparable as far as age (mean, 57 years; range, 21 to 84 years), sex ratio (71 males, 28 females), weight (mean, 66 kg; range, 40 to 69 kg), indication for surgery (first surgery, 48 patients; recurrence, 37 patients), previous anticancer treatment (surgery, radiation therapy, chemotherapy), type of surgery, and stage of cancer. The overall infection rate (wound, bacteremia, and bronchopneumonia) within 20 days after surgery was 20 patients in each group. Wound infections occurred in 14 (33%) sulbactam-ampicillin-treated patients and 9 (21%) clindamycin-amikacin-treated patients (P = 0.19; not significant). The rates of bacteremia were 2 and 4%, respectively. The rates of bronchopneumonia were 14.3 and 23.2%, respectively (P was not significant). Most infections were polymicrobial, but strict anaerobes were recovered only from patients who received sulbactam-ampicillin. Antimicrobial treatment was required within 20 days after surgery for 42% of the sulbactam-ampicillin-treated patients and 44% of the clindamycin-amikacin-treated patients. By comparison with previous studies, we observed a decreased efficacy of antimicrobial prophylaxis in patients with head and neck cancer undergoing surgery because of the increased proportion of patients who were at very high risk for infection (extensive excision and plastic reconstruction in patients with recurrent stage III and IV cancers) and because of the longer duration of surgery. PMID- 1416897 TI - In vitro susceptibility of Mycobacterium kansasii to clarithromycin. AB - The MICs of the macrolide clarithromycin for 31 clinical isolates of Mycobacterium kansasii were determined by three different methods. The methods employed were the proportion resistance method on 7H10 agar, the radiometric (BACTEC) method, and the T100 method of datum analysis. All methods gave similar results. The MICs were in a narrow range from 0.16 to 0.50 microgram/ml, with the MICs for 90% of isolates tested of 0.50 microgram/ml for the agar dilution and radiometric methods and 0.37 microgram/ml for the T100 method. The MBCs were determined for nine representative isolates by the radiometric broth method. The MBCs were equal to the MICs for four isolates, and the MBCs were twofold higher than the MICs for five isolates. Killing of 99.9% of the bacterial population was achieved at a clarithromycin concentration of 2.0 micrograms/ml for all nine isolates tested. PMID- 1416896 TI - Greatly enhanced inhibition of human immunodeficiency virus type 1 replication in CEM and HT4-6C cells by 3'-deoxythymidine diphosphate dimyristoylglycerol, a lipid prodrug of 3'-deoxythymidine. AB - 3'-Deoxythymidine (3dT) is a weakly active dideoxynucleoside in human immunodeficiency virus (HIV)-infected cells because of its slow phosphorylation by cellular thymidine kinase. 3dT diphosphate dimyristoylglycerol (3dTDP-DMG), a phospholipid prodrug, was synthesized and found in vitro to be 18- to 50-fold more effective than 3dT in CEM and HT4-6C cells. In CEM cells, the selectivity index of 3dTDP-DMG was 270 versus 48 for 3dT, an increase of 5.6-fold. In thymidine kinase-deficient mutant CEM cells infected with HIV, 3dT and zidovudine (AZT) were virtually inactive but 3dTDP-DMG retained substantial activity, suggesting that its greatly increased antiviral activity is due in part to bypass of thymidine kinase. 3dTDP-DMG was 14- to 37-fold more active than 3dT in AZT sensitive and AZT-resistant clinical isolates of HIV; no cross-resistance with AZT was noted. The results suggest that lipid prodrugs may be utilized in some cases to confer unique metabolic advantages over the corresponding free nucleoside; in the case of 3dTDP-DMG, an 18- to 50-fold increase in antiretroviral activity was observed in LAV-infected cells. The strategy would seem to be especially useful for antiviral nucleosides which are poorly phosphorylated. PMID- 1416898 TI - Inhibition of intrahepatic hepatitis B virus replication by antiviral drugs in a novel transgenic mouse model. AB - Transgenic mice which carry the integrated human hepatitis B virus (HBV) genome and produce HBV particles in the liver were treated with antiviral compounds, and the amount of viral DNA in the liver and serum was monitored by Southern analyses. Mouse alpha interferon (200,000 U per injection, twice daily for 3 days) and a novel nucleoside, oxetanocin G (15 mg/kg of body weight per injection, twice daily for 7 days), inhibited viral DNA synthesis in the liver almost completely. This animal model should prove useful in evaluating anti-HBV agents. PMID- 1416899 TI - Susceptibilities of members of the Bacteroides fragilis group to 11 antimicrobial agents. AB - The susceptibilities of 200 clinical isolates of the Bacteroides fragilis group to 11 antimicrobial agents were determined by the broth microdilution method of the National Committee for Clinical Laboratory Standards. All isolates were susceptible to imipenem and ticarcillin-clavulanic acid. The rates of resistance to cefoxitin and clindamycin were low (4 and 6%, respectively), while those to ceftizoxime and cefotetan were higher (10.5 and 24%, respectively). PMID- 1416900 TI - Pseudomonas aeruginosa biofilm as a diffusion barrier to piperacillin. AB - Pseudomonas aeruginosa 579 biofilms formed on dialysis membranes retarded piperacillin diffusion. Treatment of biofilms with 5.0 mM CaCl2.2H2O prevented diffusion. Biofilms permitted equilibration of [14C]glucose. Thin-layer chromatography of fluids distal to untreated (viable and nonviable) and viable Ca(2+)-treated P. aeruginosa 579 biofilms and fluids distal to a viable P. aeruginosa mutant noninducible for the expression of beta-lactamase did not detect piperacillinoic acid. PMID- 1416902 TI - Bioavailability of rifampin in experimental murine tuberculosis. PMID- 1416901 TI - Effect of biliary obstruction on the hepatic excretion of imipenem-cilastatin. AB - The biliary excretion of imipenem-cilastatin studied by endoscopic cannulation of the common bile duct in patients with complete obstruction and in a group without obstruction showed that despite a 24-h prophylaxis, the bile obtained from patients with obstruction immediately after cannulation contained neither imipenem nor cilastatin, while there were 2 and 5% of peak concentrations in serum for imipenem and cilastatin, respectively, in the bile from patients without obstruction. Biliary excretion of both compounds increased rapidly after decompression, reaching a maximum of 15% of peak levels in serum within 2 h. Twenty-four hours after drainage, the biliary excretion of the drugs further improved. We conclude that since biliary obstruction impairs excretion of antibiotics, drainage is necessary for the control of sepsis in obstructed cholangitis. PMID- 1416903 TI - Immunotoxic potential of antiviral drugs: effects of ganciclovir and (S)-1-(3 hydroxy-2-phosphonylmethoxy propyl) cytosine on lymphocyte transformation and delayed-type hypersensitivity responses. AB - In the present studies, we examined the in vitro and in vivo effects of ganciclovir (DHPG) and a relatively new nucleoside analogue, (S)-1-(3-hydroxy-2 phosphonylmethoxy propyl) cytosine (HPMPC), on lymphocyte responses to T cell mitogens and delayed-type hypersensitivity (DTH) responses to dinitrofluorobenzene (DNFB). Initially, responses of mouse splenic mononuclear cells and human peripheral blood mononuclear cells to PHA and con A were evaluated in vitro in the presence of each drug. Both drugs inhibited the responses to each mitogens; however, DHPG had a greater inhibitory effect on con A responses of human and mouse lymphocytes than did HPMPC. Also, spleen cells from mice treated for 7 days with DHPG responded less well to PHA stimulation than cells from untreated or HPMPC-treated mice. No effect of either drug was observed on con A responses. Treatment of mice with either drug decreased the development of DTH responses, with HPMPC having a greater inhibitory effect than DHPG. The results from the present studies suggest that both DHPG and HPMPC may have inhibitory effects on the development of certain immune functions at high dosages, but at drug concentrations that were therapeutic in animal model studies, little inhibitory effects were observed. PMID- 1416904 TI - Inhibition of human immunodeficiency viral replication by tannins and related compounds. AB - Among 87 chemically defined tannins and related compounds, several hydrolyzable tannins, but not condensed tannins or other lower molecular weight polyphenols, significantly inhibited both the cytopathic effect of human immunodeficiency virus (HIV) and the expression of HIV antigen in human lymphotropic virus type I (HTLV-1)-positive MT-4 cells. The 50% effective concentrations (2.0-4.8 micrograms/ml) of the active compounds were 13- to 15-fold lower than their 50% cytotoxic concentrations. Their anti-HIV activity was demonstrated to be mediated, at least in part, by inhibition of HIV adsorption to the cells. PMID- 1416906 TI - Drug targeting systems for antiviral agents: options and limitations. PMID- 1416905 TI - Effects of Phyllanthus plant extracts on duck hepatitis B virus in vitro and in vivo. AB - The effects of extracts of five Australian Phyllanthus species (P. hirtellus, P. gunnii, P. gasstroemii, P. similis and P. tenellus), other plant extracts and the antiviral drug foscarnet on duck hepatitis B virus (DHBV) endogenous DNA polymerase (DNAp) activity were compared. All 5 Phyllanthus species caused 50% inhibition at concentrations of dry weight between 350-800 micrograms/ml, which is comparable with the effect described for P. amarus on the DNAp of human and woodchuck hepatitis B viruses. Incubation of P. hirtellus with 100 ID50 DHBV neutralized infection. However, neither P. gasstroemi extract, given by intraperitoneal injection (i.p.) at a dose of 20 mg/kg 3 times per week to ducklings early in the incubation period, or P. hirtellus extract, given to established DHBV carrier ducklings, prevented or eliminated infection. PMID- 1416907 TI - Topical delivery of liposomally encapsulated gamma-interferon. AB - The extent of uptake of gamma interferon (gamma-IFN) in various strata of hairless mouse, human and hamster skin upon application of a liposomal formulation and an aqueous solution were determined by in vitro diffusion cell experiments. For each of the animal species studied, 70-80% of the liposomally entrapped IFN was deposited onto or penetrated into the skin as determined 24 h after in vitro application. However, a significant fraction of this total amount (approximately 0.25-0.30) is either adsorbed to or associated with the stratum corneum. The drug content found in the deeper skin strata, where the receptor sites reside, suggests that drug deposition is strongly influenced by the skin species tested. The percent of applied drug found in this strata 24 h after application followed the order: hamster (6.1) much greater than human (0.9) greater than hairless mouse (0.3), although the amounts of drug in the total skin of each species tested were approximately the same. This indicates that the deposition of drug into the living epidermis and/or dermis cannot be predicted by determination of the amount of drug in the total skin. The amounts in the deeper skin strata were also in the order of increasing number of follicles/hair in the skin species, suggesting that the transfollicular route is an important pathway for liposomal topical therapeutics. PMID- 1416908 TI - An ELISA system for evaluating antiretroviral activity against Rauscher murine leukemia virus. AB - A system for evaluating the activity of antiviral agents against Rauscher murine leukemia virus (R-MuLV) has been developed using an enzyme linked immunosorbent assay technique. The activity of various antiviral compounds demonstrated in this assay system has been compared to their activity in the UV-XC plaque reduction assay, which has been used historically for evaluating anti-R-MuLV compounds. The assay is based upon detection of R-MuLV encoded p30 protein production in virus infected murine cells. The assay reagents are readily available and the assay system is amenable to automated data collection systems. Cytotoxicity evaluations are conducted in parallel to the Rauscher MuLV ELISA assay in order to assess drug-induced reductions in cell viability. Cytotoxicity evaluations are important to interpretation of the ELISA results since reductions in cell viability reduce viral protein production which would indicate an antiviral drug effect. This system is less sensitive than the classical UV-XC plaque reduction assay; however, it does offer an alternative to the time-consuming and labor-intensive plaque assay. PMID- 1416909 TI - A new and potent 2-5A analogue which does not require a 5'-polyphosphate to activate mouse L-cell RNase L. AB - In order to explore the possibility of supplanting the requirement of a 5' triphosphate moiety for the activation of the 2-5A-dependent endonuclease (RNase L) of mouse L-cells, two new tetrameric analogues of 2-5A were synthesized. The first tetramer, obtained by both a modified prebiotic synthetic approach as well as a phosphite triester solid phase oligonucleotide synthesis method, was p5'A2'p5'A2'p5'(br8A)2'p5'(br8A). The second oligonucleotide was derived from the former by a sequence involving periodate oxidation, reaction with n-hexylamine, and cyanoborohydride reduction, resulting in conversion of the 2'-terminal adenosine residue to 9-(3'-aza-4'-hexyl-1',2',3',4'-tetradeoxyhexopyranos-1(1) yl)-8-++ +bromoadenine. Both of these oligomers, bearing only 5'-monophosphate groups, were found to be as potent as 2-5A itself as activators of the RNase L of mouse L-cells. PMID- 1416910 TI - Baculovirus expressed herpes simplex virus type 1 glycoprotein C protects mice from lethal HSV-1 infection. AB - A recombinant baculovirus (vAc-gC1) was constructed that expresses the glycoprotein C (gC) gene of herpes simplex virus type 1 (HSV-1). When Sf9 cells were infected with this recombinant, a protein that was smaller in size than authentic HSV-1 gC was detected by Western blotting using anti-gC polyclonal antibody. The recombinant gC was susceptible to tunicamycin, partially resistant to Endo-H, and was found on the membrane of Sf9 cells. Antibodies raised in mice to recombinant gC reacted with gC from HSV-1 infected cells and neutralized the infectivity of HSV-1 in vitro. Immunized mice were protected from lethal challenge with HSV-1. PMID- 1416911 TI - Virucidal effect of murine duodenal extracts: studies with lactate dehydrogenase elevating virus. AB - Mucosal resistance to infection with lactate dehydrogenase-elevating virus (LDV) has been previously demonstrated, and the LDV system presents an important murine model for the study of mucosal barriers to viral infection. In the present study, duodenal molecules were isolated from normal mice which had potent virucidal activity, when tested against LDV as well as canine herpes, canine hepatitis, Semliki forest, and visna viruses. The virucidal activity was demonstrated to be non-immune in nature, and was present in apparently non-enzymatic protein molecules, having a molecular mass of between 10-100 kDa by membrane filtration and 10-17 kDa by gel filtration. The anti-LDV activity of these molecules was suppressed by anti-duodenum antibodies in vitro, and in vivo studies suggested a possible protective role for the anti-viral molecules. We conclude that the normal mouse duodenum contains potent virucidal molecules, which are of interest to the study of biological and molecular mechanisms of viral resistance. PMID- 1416912 TI - Purification and characterization of the phosphoenolpyruvate carboxylase from the facultative chemolithotroph Thiobacillus novellus (ATCC 8093). AB - Phosphoenolpyruvate carboxylase (EC4.1.1.31), which catalyzes the carboxylation of phosphoenolpyruvate to produce oxaloacetate was purified 465-fold from extracts of organotrophically grown Thiobacillus novellus. Nondenaturing polyacrylamide gel electrophoresis (PAGE) of the purified enzyme revealed the presence of two bands after staining with Buffalo Black. Gels stained with Fast Violet B after incubation with PEP, HCO3-, Mg2+ and acetyl CoA also showed two bands of activity with the faster moving the more active of the two. Sodium dodecylsulfate (SDS)-PAGE of the enzyme heated at 100 degrees C for 5 min revealed the presence of three intensely stained bands of M(r) 95 K, 51 K, and 28 K. However, electrophoresis of the enzyme heated for 2 min showed a single band of about 100 K, indicating that the preparation was likely homogeneous. The 51 K and 28 K subunits are thus products of the 95 K subunit. Gel filtration studies of the native enzyme yielded a M(r) of 360 K. Therefore, the enzyme is a tetramer. The optimum pH in Tris buffer was 8.0, with Km for PEP 0.64 mM, HCO3- 0.11 mM, and acetyl CoA a potent activator, 1.3 microM. A divalent cation best served by Mg2+ gave sigmoidal initial velocity plots. Hill plots of the data gave coefficients (nH) of 2.6. None of the metabolites tested, nucleotide triophosphates excepted, significantly affected enzyme activity. Binding studies with 14C-labelled PEP revealed the binding of about 20 moles PEP per mole (360,000 g) of PEPC. Initial velocity studies suggest that the reaction is catalyzed by a random Bi Bi mechanism. Despite the lack of inhibition by certain metabolites, the enzyme's function is probably anaplerotic. PMID- 1416913 TI - Isolation of auxotrophic mutants of the methylotrophic yeast Candida boidinii and determination of its ploidy. AB - Auxotrophic mutations in the methylotrophic yeast strain Candida boidinii 11Bh were induced by different mutagens and their combinations (nitrosoguanidine, UV light, HNO2+UV). Majority of the mutants obtained carried defects in histidine, arginine, proline and/or adenine biosynthetic pathways. His- mutants were distributed into four complementation groups using the protoplasts fusion technique. Ploidy determination of Candida boidinii 11Bh was performed by measuring its DNA content and by following its survival after chemical mutagens treatment. The DNA content of this strain was found to be similar to that of a Saccharomyces cerevisiae diploid strain. Also the kinetics of survival of Candida boidinii cells indicate that Candida boidinii 11Bh is a diploid. PMID- 1416914 TI - Degradation of some phenols and hydroxybenzoates by the imperfect ascomycetous yeasts Candida parapsilosis and Arxula adeninivorans: evidence for an operative gentisate pathway. AB - The imperfect ascomycetous yeasts Candida parapsilosis and Arxula adeninivorans degraded 3-hydroxybenzoic acid via gentisate which was the cleavage substrate. 4 Hydroxybenzoic acid was metabolized via protocatechuate. No cleavage enzyme for the latter was detected. In stead of this NADH- and NADPH-dependent monooxygenases were present. In cells grown at the expense of hydroquinone and 4 hydroxybenzoic acid, enzymes of the hydroxyhydroquinone variant of the 3 oxoadipate pathway were demonstrated, which also took part in the degradation of 2,4-dihydroxybenzoic acid by C. parapsilosis. PMID- 1416915 TI - Formation of antigenic extracellular polysaccharides by selected strains of Mucor spp., Rhizopus spp., Rhizomucor spp., Absidia corymbifera and Syncephalastrum racemosum. AB - In this study, polyclonal IgG antibodies raised against extracellular polysaccharides (EPS) of Mucor racemosus were characterised as almost specific for moulds belonging to the order of Mucorales. Cross-reactivity in the ELISA could be observed only towards the yeast Pichia membranaefaciens. EPS were isolated from various cultures of M. hiemalis growing on six different carbon sources and two nitrogen sources, with ratios varying from 0.13 to 0.44 relative to the amount of biomass. Other strains including Mucor spp., Rhizopus spp., Rhizomucor spp., Absidia corymbifera and Syncephalastrum racemosum also excreted EPS, with ratios varying from 0.05 to 0.23. In all cases, the excreted EPS had similar antigenic properties as determined by ELISA. No enzymatic degradation of the antigenic parts of the polysaccharides could be observed upon prolonged incubation. Considering that all tested strains formed similar amounts of antigenic EPS there might be scope for the specific detection of biomass of Mucoralean moulds using ELISA techniques for example in food. PMID- 1416916 TI - Purification and characterization of an NAD(+)-linked formaldehyde dehydrogenase from the facultative RuMP cycle methylotroph Arthrobacter P1. AB - When Arthrobacter P1 is grown on choline, betaine, dimethylglycine or sarcosine, an NAD(+)-dependent formaldehyde dehydrogenase is induced. This formaldehyde dehydrogenase has been purified using ammonium sulphate fractionation, anion exchange- and hydrophobic interaction chromatography. The molecular mass of the native enzyme was 115 kDa +/- 10 kDa. Gel electrophoresis in the presence of sodium dodecyl sulphate indicated that the molecular mass of the subunit was 56 kDa +/- 3 kDa, which is consistent with a dimeric enzyme structure. After ammonium sulphate fractionation the partially purified enzyme required the addition of a reducing reagent in the assay mixture for maximum activity. The enzyme was highly specific for its substrates and the Km values were 0.10 and 0.80 mM for formaldehyde and NAD+, respectively. The enzyme was heat-stable at 50 degrees C for at least 10 min and showed a broad pH optimum of 8.1 to 8.5. The addition of some metal-binding compounds and thiol reagents inhibited the enzyme activity. PMID- 1416917 TI - Systematic placement of the basidiomycetous yeast Cystofilobasidium lari-marini comb. nov. as predicted by rRNA nucleotide sequence analysis. AB - Based on similarities in basidial morphology and nucleotide sequences of the V3 variable region in the large sub-unit ribosomal RNA, the yeast Leucosporidium lari-marini is considered phylogenetically related to the genus Cystofilobasidium. Therefore the new combination Cystofilobasidium lari-marini is proposed. PMID- 1416918 TI - Hyalohyphomycosis caused by Paecilomyces variotii: a case report, animal pathogenicity and 'in vitro' sensitivity. AB - A case of cutaneous infection in a 25-year-old male caused by Paecilomyces variotii is described. Animal pathogenicity studies with normal and cortisone treated mice revealed the predeliction of P. variotii for skin and liver in both normal and cortisone-treated mice and for lungs and heart only in immunosuppressed mice. 5-fluorocytosine gave the best MIC value for P. variotii in vitro. This report documents for the first time that P. variotii causes cutaneous infection. PMID- 1416919 TI - Heterotrophic nitrification and aerobic denitrification in Alcaligenes faecalis strain TUD. AB - Heterotrophic nitrification and aerobic and anaerobic denitrification by Alcaligenes faecalis strain TUD were studied in continuous cultures under various environmental conditions. Both nitrification and denitrification activities increased with the dilution rate. At dissolved oxygen concentrations above 46% air saturation, hydroxylamine, nitrite and nitrate accumulated, indicating that both the nitrification and denitrification were less efficient. The overall nitrification activity was, however, essentially unaffected by the oxygen concentration. The nitrification rate increased with increasing ammonia concentration, but was lower in the presence of nitrate or nitrite. When present, hydroxylamine, was nitrified preferentially. Relatively low concentrations of acetate caused substrate inhibition (KI = 109 microM acetate). Denitrifying or assimilatory nitrate reductase were not detected, and the copper nitrite reductase, rather than cytochrome cd, was present. Thiosulphate (a potential inhibitor of heterotrophic nitrification) was oxidized by A. faecalis strain TUD, with a maximum oxygen uptake rate of 140-170 nmol O2.min-1.mg prot-1. Comparison of the behaviour of A. faecalis TUD with that of other bacteria capable of heterotrophic nitrification and aerobic denitrification established that the response of these organisms to environmental parameters is not uniform. Similarities were found in their responses to dissolved oxygen concentrations, growth rate and ammonia concentration. However, they differed in their responses to externally supplied nitrite and nitrate. PMID- 1416920 TI - Kluyveromyces piceae sp. nov., a new yeast species isolated from the rhizosphere of Picea abies (L.) Karst. AB - Two strains of an undescribed species of the genus Kluyveromyces were recovered from the rhizosphere of spruce. A description of the new species, Kluyveromyces piceae, is given and its classification on basis of ascospore shape, substrate utilization, G+C-content, DNA-DNA-reassociation data and habitat specificity is discussed. PMID- 1416921 TI - Strike-through, gown safety. PMID- 1416922 TI - Project Team identifies practice model criteria. PMID- 1416923 TI - Pulmonary autograft. An aortic valve replacement alternative. AB - In selected patients, the pulmonary autograft procedure utilizing cryopreserved homografts for reconstruction of the right ventricular outflow tract is becoming an increasingly popular aortic valve replacement alternative. Longitudinal statistical reports show that patients need reoperation less often with this procedure. Because the valve is autogenous tissue, all indications to date show that the valve continues to function for extended periods of time in all patients and can accommodate growth in children. At the same time, transfer of the pulmonary valve to the aortic position provides a natural valvular flow pattern and freedom from the degenerative changes associated with bioprosthetic valves or the need for anticoagulation associated with mechanical valves. PMID- 1416924 TI - Kock pouch. An internal ileal reservoir for continent urinary diversion. PMID- 1416925 TI - Disaster planning. Realistic ideas for the operating room. PMID- 1416926 TI - Reconceptualizing, redefining perioperative nursing. Project Team Report. PMID- 1416927 TI - Recommended practices. Disinfection. Association of Operating Room Nurses. PMID- 1416928 TI - Recommended practices. Steam and ethylene oxide (EO) sterilization. Association of Operating Room Nurses. PMID- 1416929 TI - Social aspects of urinary incontinence in the elderly. PMID- 1416930 TI - Standards of practice, recent changes; preparing job descriptions that reflect these standards; how these standards relate to practice. PMID- 1416931 TI - Technician starting lines; counts when a patient dies; count documentation; lay terms on permit; drug abuse rehabilitation. PMID- 1416932 TI - States tackle health care reform. PMID- 1416933 TI - Development of tolerance to endogenous opiates activated by 24-h food deprivation. AB - Four experiments assessed the effects of exposure to 24-h food deprivation on the tail-flick latency of rats exposed to a temperature stimulus. Confirming previous studies, Experiment 1 showed that food deprivation gave rise to analgesia, as indicated by increased tail-flick latencies, that was antagonized by naloxone. Experiment 2 found that analgesia was greatly reduced after five exposures to periods of 24-h food deprivation (alternating with 24-h free access to food), indicating the development of tolerance. Experiments 3 and 3a examined the development of tolerance to the analgesic effects of morphine following repeated morphine injections, saline injections, and exposure to 24-h food deprivation plus saline injections. The combined results of both experiments provided evidence that repeated exposures to either morphine or food deprivation, produced greater tolerance to morphine than did exposures to saline. That food deprivation was cross-tolerant with morphine indicated that tolerance to food deprivation induced analgesia involved opioid mechanisms. The relevance of opioid tolerance to psychobiological models of feeding and to the development of an animal model of anorexia nervosa was discussed. PMID- 1416934 TI - Factors influencing sensory-specific satiety. AB - In the first part of this study, subjects tasted small portions of a set of foods (rating set) and rated their liking of these foods before and after eating a serving of one of the foods (test meal). These foods were chosen to vary in both macronutrient composition and sensory qualities. Measurements of hunger were taken before and after the test meal. The amount of sensory-specific satiety produced by a test meal differed depending on the food eaten. There was a trend for high-protein foods, which were also the least-liked foods, to decrease more in liking than low-protein foods. Buttered rolls and Coke, when eaten as test meals, dropped the least in liking. Initial liking and the variety of sensory qualities within a food were investigated as potential factors which could influence sensory-specific satiety. Subjects tasted and rated their liking of the test meals, which varied in the level of initial liking and the level of variety of sensory qualities within a food, before and after eating. There was a non significant trend for the less-liked test meals to drop more in liking than the well-liked test meals. There was also a slight trend for the low-variety test meals to drop slightly more in liking than the intermediate and high-variety test meals. PMID- 1416935 TI - Predictors of adult humans' self-control and impulsiveness for food reinforcers. AB - Humans vary in the degree to which they demonstrate self-control--choice of larger, more delayed over smaller, less delayed reinforcers. When reinforcers consist of food, individual human subjects' choice behavior varies from virtually exclusive self-control to exclusive impulsiveness. The present experiment, using 26 men and 26 women subjects, explored some possible sources of this individual variation through assessing the correlation of behaviors exhibited in the self control paradigm with various subject characteristics. The results suggest that self-control is negatively related to individuals' reported susceptibility to hunger (Factor 3 of the Three-Factor Eating Questionnaire) and positively related to overall rating of juice desirability, but not to gender or to various measures of caloric deprivation or personality. Relatively high self-perceived levels of food deprivation may decrease self-control, whereas assigning a relatively high value to the reinforcer may increase self-control. Both tendencies would have been adaptive for evolving humans. PMID- 1416936 TI - Methodology and theory in human eating research. AB - Current research in human eating is assessed from the perspective of current research methods which stress laboratory research, the use of artificial foods rather than real meals, shorter term studies, animal models, and abnormal eating models and an emphasis on sensory and physiological factors rather than social, cultural and contextual factors. The proposal is made to refocus more human eating research on real people eating real foods in real eating situations. PMID- 1416937 TI - Towards scientific realism in eating research. PMID- 1416938 TI - Where should human eating be studied and what should be measured? AB - Meiselman's (1992) proposal for redirection of research on human eating behavior towards eating in real settings is misdirected, because it does not take into consideration the questions being addressed by laboratory studies. In fact many of the studies for which he has called have in fact been done and will be cited. There is no compelling scientific or strategic reason that investigators who are making good progress on the problem of what controls the amount eaten should be exhorted to examine what controls the place or time of eating or what is selected for eating. They are different problems which require different methodology. The field is large enough for both kinds of studies and there is no reason to berate investigators as Meiselman does for not investigating the problem he happens to be studying. PMID- 1416939 TI - Real people, real foods, real eating situations: real problems and real advantages. PMID- 1416940 TI - Let's not throw out the barley with the dishwater. PMID- 1416941 TI - Both naturalistic and laboratory-based studies contribute to the understanding of human eating behavior. PMID- 1416942 TI - Real eating and the measurement of real physiological and behavioral variables. PMID- 1416943 TI - When is eating "real"? PMID- 1416944 TI - Kinetics and activity distribution of urease coencapsulated with hemoglobin within polyamide membranes. AB - A 91.5% mass yield of urease and hemoglobin (Hb), co-encapsulated within polyamide membranes, was determined spectrophotometrically. The specific activity yield of microencapsulation was 84%, twofold higher than values previously reported, as a result of optimization of encapsulation conditions. The kinetic parameters and pH activity profiles of intracapsular urease were determined to be similar to those corresponding to the free enzyme. Similar activities were also observed for intact and microcapsule homogenate, indicating minimal mass transfer and diffusional limitation. The active configuration of the enzyme appears to remain intact upon microencapsulation. The application of a kinetic model for encapsulated urease further indicated that the kinetics were reaction-controlled with minimal mass transfer restrictions. PMID- 1416945 TI - Rapid determination of immobilized ConA lectin activity. AB - ConA was immobilized on an epoxy-activated copolymer of 2-hydroxyethyl methacrylate and ethylene-dimethacrylate and commercially available high-pressure liquid chromatography (HPLC) sorbents Separon HEMA 1000 EL, Separon HEMA 1000 E, and Separon HEMA 1000 EH (Tessek, Prague, CSFR Denmark). Specific, sensitive, and rapid method for determination of immobilized ConA lectin activity was developed. beta-Galactosidase from Aspergilus oryzae oligomannosyl residues was used as specific affinant. After separation of bound and unbound beta-galactosidase, enzyme activity was measured in supernatant and thus immobilized ConA lectin activity was calculated easily. The use of the method for evaluating the properties of immobilized ConA, efficiency of immobilization, specific activity, and thermostability is shown. The method developed could be generalized by using artificially glycosylated enzyme for any lectin. PMID- 1416946 TI - Biological deodorization of dimethyl sulfide using different fabrics as the carriers of microorganisms. AB - Biological deodorization of dimethyl sulfide (DMS) was studied using nine unwoven fabrics as the carriers of microorganisms in a laboratory-scale deodorizing system. The activated carbon fabric FN-200CF-15 was the best packing material compared with other packing materials used, on the basis of removal rate. The maximum removal rate (Vm), evaluated by using Michaelis-Menten equation, was 2.28 g-S.kg-dry fab.-1.day-1 in this fabric biofilter. The critical load of DMS in this fabric biofilter was dependent on space velocity (SV), determined as 0.78 and 0.66 g-S.kg-dry fab.-1 at SV 100 and 150 h-1, respectively. Strain IM1 isolated from the carbon fabric FN-200CF-15 biofilter in modified Waksman (MW) medium successfully degraded DMS as well as hydrogen sulfide (H2S), methanethiol (MT), and dimethyl disulfide (DMDS) in batch test. The DMS removal rates (g S.cell-1.h-1) by this strain measured in batch culture and calculated in FN-200CF 15 biofilter by the cell numbers appeared in MW medium were found almost equal, indicating that strain IM1 may be the dominant microorganism in this biofilter. PMID- 1416947 TI - Activation and detection of (pro)mutagenic chemicals using recombinant strains of Streptomyces griseus. AB - Two recombinant strains of Streptomyces griseus have been developed to report on the activation of promutagenic chemicals. This activation is monitored by reversion of the bacterial test strains to a kanamycin-resistant phenotype. Strain H69 detects point mutations and was reverted at an increased frequency by acetonitrile, 2-aminoanthracene, 1,2-benzanthracene, benzidine, benzo(a)pyrene, 9,10-dimethyl-1,2-benzanthracene, and glycine. The second strain, FS2, detects frame shift mutations and was reverted at an increased frequency by 1,2 benzanthracene, benzidine, and glycine. Compounds such as butylated hydroxytoluene, catechol, chlorobenzene, hydroquinone, potassium chloride, phenol, cis-stilbene, trans-stilbene, and toluene did not elicit positive responses in either strain. In addition, these strains are capable of detecting direct-acting mutagens such as N-methyl-N'-nitrosoguanidine and ICR-191, providing further evidence of their promise for detecting a wider range of mutagens. To our knowledge, this is the first report of bacterial strains capable of activating promutagenic compounds and detecting their mutagenic metabolites without the benefit of an exogenous activation system such as the rodent liver homogenate (S9). PMID- 1416948 TI - Actinomycetes in submerged culture. AB - The range of morphological forms of actinomycetes in shaken flask culture and fermenters is reviewed. Some of the factors that influence pellet formation and its prevention are discussed. The relationship between morphology and production of antibiotics and other metabolites is also examined. PMID- 1416950 TI - Ascorbic acid biosensor using ascorbate oxidase immobilized on alkylamine glass beads. AB - A biosensor for ascorbic acid based on enzyme kinetics of ascorbate oxidase (E.C.1.10.3.3) was developed. The enzyme was extracted from Cucurbita maxima, or jerimun and immobilized by covalent bounding, using glutaradehyde as a bifunctional agent, on alkylamine glass beads, with and without enzyme active site protection. A low-cost, home-made oxygen electrode was applied as a transducer. The system has sensitivity from 62.5 up to 500 microM of ascorbic acid with satisfactory operation for more than 2 mo. PMID- 1416949 TI - Glucoamylase immobilization on a magnetic microparticle for the continuous hydrolysis of maltodextrin in a fluidized bed reactor. AB - Glucoamylase (GA) has been successfully immobilized through its carbohydrates previously oxidized with periodate onto a low-cost magnetic microparticle made of polyethyleneimine-coated magnetite crosslinked with glutaraldehyde (M-GAD) and derivatized with adipic dihydrazide (ADH). A stabilization posttreatment consisting of crosslinking its carbohydrates with ADH, increased the remaining activity from 54 to 71%, calculated on the Vm values and measured at 50 degrees C and pH 4.5 with maltodextrin (DE 11-14) as substrate. This treatment also improved the enzyme stability and lowered the deactivation rate constant kd to a third of its value. A 30% maltodextrin solution has been continuously hydrolyzed at 50 degrees C and pH 4.5 in a recycled, fluidized bed reactor (FBR) containing GA immobilized on these magnetic microparticles. They easily settled in this highly viscous medium because of their high density (5 g/mL), and washout of ultrafines was prevented by surrounding the top of the bed with an electromagnet. The small particle size (20 microns) allowed a high enzyme loading in the reactor and also a high bed voidage, which is recommended to avoid extensive pressure drop and consequent channeling problems. The kinetic of hydrolysis fitted with the plug-flow model; this is explained by the insignificant backmixing effects observed. After 2 wk of hydrolysis under process conditions leading to a conversion of 70%, which corresponds to a high-conversion syrup, the immobilized GA only lost 4% of its initial activity. PMID- 1416951 TI - Immobilization of glucose isomerase onto granular chicken bone. AB - Glucose isomerase was immobilized onto granular chicken bone (BIOBONE) by adsorption. The amount of activity bound relative to an equal amount of free enzyme was 32 +/- 1%, with the estimated specific activity decreasing from 11.1 +/- 0.7 to 3.9 +/- 0.5 U/mg protein with immobilization. Compared with the free enzyme, immobilized glucose isomerase showed a threefold increase in the Km for fructose and a fivefold decrease in Vmax. High operating temperatures were possible (greater than 55 degrees C), but continuous use and long-term storage studies showed gradual losses of activity. Both the binding and the activity of the bone-immobilized enzyme were highly resistant to treatments with detergent, ethanol, and KCl. Studies to determine mass transfer limitation effects on immobilized glucose isomerase showed that these were insignificant for this system. PMID- 1416952 TI - Immobilization of amyloglucosidase onto granular chicken bone. AB - Amyloglucosidase was immobilized onto granular chicken bone (BIOBONE) by noncovalent interactions. The amount of activity bound relative to an equal amount of free enzyme was 13.6 +/- 0.4%. The estimated specific activity for amyloglucosidase decreased from 75.3 +/- 0.8 to 43.5 +/- 9.6 U/mg protein upon immobilization. The Km value of the bone-immobilized enzyme using glycogen as substrate increased from 3.04 +/- 0.38 mg/mL (free) to 9.04 +/- 1.51 mg/mL (immobilized), but Km showed no change upon immobilization when starches were used as substrates. A decrease in Vmax values occurred upon enzyme immobilization for all substrates, but this largely reflected the percentage of enzyme initially bound to the bone. Immobilization also improved enzyme stability in the presence of various additives (e.g., detergent, KCl, and ethanol) or under low or high pH reaction conditions. Bound amyloglucosidase maintained high activity (greater than 90%) following five cycles of continuous use at moderate (23 degrees C) and high (55 degrees C) temperatures. Data derived from Lineweaver-Burk and Arrhenius plots indicated that substrate and product diffusion limitation were minimal. PMID- 1416953 TI - Enzymatic synthesis of (R) and (S) 1-deuterohexanol. AB - This paper describes practical enzymatic procedures for the synthesis of (R) and (S) 1-deuterohexanol, a useful building block for chiral poly isocyanated liquid crystals. Alcohol dehydrogenases from horse liver and Pseudomonas catalyzed the reduction of hexanal with deuterated NAD (NADD) resulting in 50% and 89% yields of (R) and (S) 1-deuterohexanol, respectively. The deuterated cofactor was regenerated in situ by alcohol dehydrogenase catalyzed oxidation of ethanol-d6 or 2-propanol-d8. The (S) alcohol was also synthesized by the horse liver alcohol dehydrogenase reduction of 1-deuterohexanal, which was prepared chemically from hexanal. The yields of the reaction were greatly increased by the use of a biphasic system or with the immobilized enzyme in anhydrous organic solvents. Horse liver alcohol dehydrogenase was stabilized by immobilization on PAN or noncovalent entrapment on XAD resin. PMID- 1416955 TI - Weaving the web of community relationships. PMID- 1416954 TI - The study of the cultivation of Chinese hamster ovary and Bowes cell lines with poly(organophosphazene) membranes. AB - Sixteen poly(organophosphazenes) were prepared by reaction between polydichlorophosphazene (NPCl2)n and nucleophilic reagents such as phenoxides and amino compounds. Adhesive and colony formation percent were investigated using V 79 Chinese hamster cells on poly(organophosphazene) films. It was found that [NP(OC6H5)2-x(NHBu-n)x]n (x = 0.2, 1.8) gave the best percent adhesiveness. This value was similar to that of Falcon. On the other hand, [NP(OC6H5)-(NHBu-n)]n film showed best colony percent formation. This was of a higher value than that of Falcon. The [NP(OC6H5)2]n properties were poor for cultivation of useful Bowes and chinese hamster ovary cell lines in comparison with Cytodex III. PMID- 1416956 TI - Psychosocial responses among individuals with human immunodeficiency virus infection. AB - The purpose of this research was to identify and describe psychosocial responses to being infected with human immunodeficiency virus (HIV). Ten adults infected with HIV were interviewed and audiotaped as they described their feelings and experiences as HIV-infected people. The interviews were analyzed using a grounded theory methodology. The core category that emerged from the data was Fighting to Survive with HIV Infection. Supporting concepts were Taking Care and Restructuring One's Life. The concept of Taking Care included processes of everyday work and illness work. The processes involved in Restructuring One's Life were living with uncertainty, accepting homosexuality, experiencing changing feelings, protecting confidentiality, dealing with the medical profession, handling multiple losses, and living with a terminal illness. PMID- 1416957 TI - Home health nurses' assessments of cognition. AB - Assessments of mental status in elderly persons admitted to home health agencies are the basis for decision-making related to resources provided. A home health nurse's perceptions of an elderly client's capacity for self-care determines whether community services will be prescribed. In institutional settings, evaluation of cognition by professional nurses is often incomplete or inaccurate. It was the purpose of this study to compare the judgements of cognition made by nine home health nurses who were admitting elderly clients to a visiting nurse association with scores from an objective measure of mental status. Findings suggest that these nurses relied primarily on orientation as an indicator of cognitive abilities. PMID- 1416958 TI - Preoperative self-efficacy and postoperative behaviors. AB - Preoperative instruction has been found to decrease postoperative complications; however, the mechanisms through which preoperative instruction exerts its effects remain unknown. In this study, the relationship between preoperative self efficacy and postoperative behaviors was investigated. Subjects were 68 cholecystectomy patients. Subjects' scores on the efficacy expectations subscale were related significantly to postoperative deep breathing, ambulation, and recall of expected events; scores on the outcome expectations subscale were related significantly to postoperative requests for pain medication. Self efficacy theory provided a link between self perceptions and behavior and may be the mechanism through which preoperative instruction exerts its effects. PMID- 1416959 TI - Determining risk status in a primary care setting. AB - Nurses working in primary health care settings often care for large numbers of clients in brief periods of time. Both clients and nurses express frustration toward the care provided in these circumstances. Development of a screening tool to identify high-risk clients could assist nurses in targeting interventions to these individuals; in turn, this has the potential for increasing nurse and client satisfaction. A general procedure for identifying persons at risk in primary health care settings is described. The procedure is illustrated with a specific population of clients--incarcerated women. Factors found important in assessing risk were social characteristics such as education, situational factors such as sentence length, and indicators of psychological distress such as depression. These broad categories may serve as a basis for the development of screening tools for a variety of populations. PMID- 1416960 TI - Cognitive changes associated with the acquired immunodeficiency syndrome. PMID- 1416961 TI - Navigating the institutional labyrinth: clinical research strategies. PMID- 1416962 TI - Experiences of acute care nurses who seek out a nurse researcher as a preceptor. PMID- 1416963 TI - Thapsigargin, a high affinity and global inhibitor of intracellular Ca2+ transport ATPases. PMID- 1416964 TI - Expression of mouse cathepsin L cDNA in Saccharomyces cerevisiae: evidence that cathepsin L is sorted for targeting to yeast vacuole. AB - To investigate the intracellular transport mechanism of lysosomal cathepsin L in yeast cells, we attempted to produce mouse cathepsin L in Saccharomyces cerevisiae by placing the coding region under the control of the promoter of the yeast glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. Immunoblotting analysis by the use of an antibody specific for rat cathepsin L revealed that the yeast cells carrying the cathepsin L coding sequence produced 39- and 30-kDa products, which correspond to the rat procathepsin L and the single-chain form of mature cathepsin L, respectively. The precursor polypeptide showed sensitivity toward endoglycosidase H treatment. Cell fractionation experiments demonstrated that the processed form of 30-kDa cathepsin L was found to be colocalized to the yeast vacuole with the marker enzyme carboxypeptidase Y in a Ficoll step gradient. In the prepared vacuolar fraction, a considerable amount of cathepsin L was revealed to be cofractionated with the vacuolar membranes. Furthermore, the phase separation experiments with Triton X-114 provide the first evidence showing that the mature form of cathepsin L polypeptide is strongly associated with the vacuolar membranes. Therefore, the present results suggest that the mouse cathepsin L precursor polypeptide is initially synthesized as the proenzyme in the yeast cells and then correctly delivered to the vacuole. During the intracellular sorting pathway, the procathepsin L would undergo the post translational proteolytic processing step to generate the mature enzyme. Based on these lines of evidence, we propose that cathepsin L is recognized by mechanisms similar to those for the intracellular sorting and processing of vacuolar proteins in the yeast cells. PMID- 1416965 TI - Slow-onset inhibition of ribosomal peptidyltransferase by lincomycin. AB - In a system derived from Escherichia coli, we carried out a detailed kinetic analysis of the inhibition of the puromycin reaction by lincomycin. N Acetylphenylalanyl-tRNA (Ac-Phe-tRNA; the donor) reacts with excess puromycin (S) according to reaction [1], C+S Ks <--> CS k3 --> C'+P, where C is the Ac-Phe-tRNA poly(U)-ribosome ternary complex (complex C). The entire course of reaction [1] appears as a straight line when the reaction is analyzed as pseudo-first-order and the data are plotted in a logarithmic form (logarithmic time plot). The slope of this straight line gives the apparent ksobs = k3[S]/(Ks + [S]). In the presence of lincomycin the logarithmic time plot is not a straight line, but becomes biphasic, giving an early slope (ke = k3[S]/(Ks(1 + [I]/Ki) + [S])) and a late slope (k1 = k3[S]/(Ks(1 + [I]/K'i + [S])). Kinetic analysis of the early slopes at various concentrations of S and I shows competitive inhibition with Ki = 10.0 microM. The late slopes also give competitive inhibition with a distinct inhibition constant K'i = 2.0 microM. Excluding alternative models, the two phases of inhibition are compatible with a model in which reaction [1] is coupled with reaction [2], C+I k4 <--> k5 CI k6 <--> k7 C*I, where the isomerization step CI <--> CI* is slower than the first step C+I <--> CI, Ki = k5/k4 and K'i = Ki [k7/(k6 + k7)]. Corroborative evidence for this model comes from the examination of reaction [2] alone in the absence of S. This reaction is analyzed as pseudo first-order going toward equilibrium with kIeq = k7 + (k6 [I]/(Ki + [I])). The plot of kIeq versus [I] is not linear. This plot supports the two-step mechanism of reaction [2] in which k6 = 5.2 min-1 and k7 = 1.3 min-1. This is the first example of slow-onset inhibition of ribosomal peptidyltransferase which follows a simple model leading to the determination of the isomerization constants k6 and k7. We suggest that lincomycin inhibits protein synthesis by binding initially to the ribosome in competition with aminoacyl-tRNA. Subsequently, as a result of a conformational change, an isomerization occurs (CI <--> C*I), after which lincomycin continues to interfere with the binding of aminoacyl-tRNA to the isomerized complex. PMID- 1416966 TI - Phosphorylation of chicken oviduct progesterone receptor by cAMP-dependent protein kinase. AB - Phosphorylation of immunopurified chicken oviduct progesterone receptor (PR) was studied in intact cells and under cell-free conditions. Cytosol PR was isolated by incubation with anti-PR monoclonal antibody alpha PR22 adsorbed to protein A Sepharose and suspended in a reaction mixture containing 10 mM Mg2+, 0.1 mM [gamma-32P]ATP, and the catalytic subunit of cAMP-dependent protein kinase (cAMP PK) from bovine heart. All three major proteins of avian PR (PR-A, 79 kDa; PR-B, 110 kDa; 90 kDa) incorporated 32P-radioactivity on serine residues. The phosphorylation reaction was inhibited by synthetic inhibitors of protein kinases, H-8 and 20-residue peptide IP20. A 40 degrees C preexposure of PR oligomer increased phosphorylation of the 90-kDa protein, known to be a heat shock protein (hsp-90). The extent of the phosphorylation reaction was temperature-dependent as the 32P-incorporation into PR-A and PR-B increased gradually, showing a maximum at 37 degrees C. Multiple phosphopeptides (4-7) were resolved by two-dimensional electrophoresis chromatography following cleavage of 32P-labeled peptides with trypsin. Both A and B forms of receptor showed similar phosphorylation patterns with B receptor digestion exhibiting two to three additional peptides. Under physiological conditions, preincubation of oviduct mince with forskolin, a regulator of intracellular cAMP levels, caused a greater extent of phosphorylation of PR-A and PR-B proteins. The results of this study demonstrate that chicken oviduct PR is an excellent substrate for the action of cAMP-PK in vitro and that this enzyme may be a physiological regulator of progesterone action in the oviduct. PMID- 1416967 TI - Analysis of catalytic properties of hen egg white lysozyme during renaturation from denatured and reduced material. AB - Catalytic properties of hen egg white lysozyme were analyzed during the renaturation of the enzyme from completely reduced and denatured material. The formation of intermediate folding products and the generation of native lysozyme was monitored by acetic acid/urea electrophoresis. The results showed that during the beginning of renaturation almost all reduced and denatured lysozyme is converted to forms possessing lower compactness than native lysozyme, probably as a result of formation of only one or two disulfide bonds. Kinetic analysis of lysozyme during renaturation showed that the generation of lysozyme with four disulfide bonds was not necessarily equivalent to the formation lysozyme with native-like catalytic properties. It appeared that the formation rate of the structures of the structures of the substrate binding site and of the catalytic site were limited by the generation of four disulfide bonds containing lysozyme. The catalytic properties of intermediate folding products made it evident that the final structures of the substrate binding site and of the catalytic site were formed after the generation of all disulfide bonds. PMID- 1416968 TI - Cleavage of xyloglucan by nasturtium seed xyloglucanase and transglycosylation to xyloglucan subunit oligosaccharides. AB - Oligosaccharide subunits were prepared from xyloglucan (XG) by partial hydrolysis with cellulase and added back at micro- to millimolar concentrations to XG in the presence of nasturtium seed xyloglucanase (XG-ase). The oligosaccharides (0.2 mM) stimulated the capacity of this XG-ase to reduce the viscosity of XG solutions by 10- to 20-fold. Purification and fractionation of seed XG-ase activity by gel permeation fast protein liquid chromatography produced a single peak that was much more active in the presence than absence of added XG oligosaccharide. [14C]Fucose-labeled XG nonasaccharide was synthesized by pea fucosyltransferase and shown to be incorporated into polymeric XG in the presence of seed XG-ase without the net production of new reducing chain ends, even while the loss of XG viscosity and XG depolymerization were enhanced. It is concluded that in vitro seed XG-ase can transfer cleavage products of XG to XG oligosaccharides via endotransglycosylation reactions, thereby reducing XG M(r) without hydrolysis. Since this is the only XG-cleaving enzyme that develops in nasturtium seeds during germination, it may be that its transglycosylase and hydrolase capacities are both necessary to account for the rapid and complete depolymerization of XG that takes place. PMID- 1416969 TI - Effects of MgCl2 on the release and recycling of heparan sulfate proteoglycans in a rat parathyroid cell line. AB - Divalent cations, such as Mg2+, Ba2+, and Co2+, are known to mimic the effects of Ca2+ in parathyroid cells, but it is not clear whether the mechanism of their action is the same as that of Ca2+. We have shown that extracellular Ca2+ concentration ([Ca2+]e) regulates the distribution and recycling of cell-surface heparan sulfate (HS) proteoglycans in a rat parathyroid cell line; at normal to high [Ca2+]e (e.g., 2 mM) HS proteoglycans are primarily localized intracellularly, while at low [Ca2+]e (0.05 mM) they are translocated to the cell surface and rapidly recycle (Takeuchi, Y., Sakaguchi, K., Yanagishita, M., Aurbach, G. D., and Hascall, V. C., 1990, J. Biol. Chem. 265, 13661-13668). We now show that a high concentration of Mg2+ (8 mM) reduces the amount of recycling HS proteoglycans in low [Ca2+]e. However, the primary effects of high Ca2+ and high Mg2+ on the recycling HS proteoglycans are different. High [Ca2+]e causes translocation of HS proteoglycans to intracellular compartments, while high Mg2+ stimulates cleavage of their core proteins and subsequent shedding of HS proteoglycans into the medium, thereby depleting the recycling molecules. However, high Mg2+ does not induce shedding of HS proteoglycans in high [Ca2+]e. The effects of Ba2+ and Co2+ were similar to those of Mg2+, but Sr2+ showed no significant effects on HS proteoglycan translocation. Otherwise, 8 mM Mg2+ did not alter biosynthesis or intracellular catabolism of HS proteoglycans. These observations suggest that the recycling of HS proteoglycans in parathyroid cells is sensitive only to [Ca2+]e, whereas several other divalent cations can deplete the recycling HS proteoglycans by a distinctly different mechanism. Thus, the mechanism by which Ca2+ regulates the amounts of the recycling HS proteoglycans may be more physiological and play a functional role in parathyroid cells. PMID- 1416970 TI - Comparative study of monomeric reconstituted and membrane microsomal monooxygenase systems of the rabbit liver. I. Properties of NADPH-cytochrome P450 reductase and cytochrome P450 LM2 (2B4) monomers. AB - Oligomers and monomers of NADPH-cytochrome P450 reductase and cytochrome P450 LM2 (2B4) isolated from the liver microsomes of phenobarbital-treated rabbits were examined for physicochemical properties and catalytic activities. As measured using laser correlation spectroscopy the particle sizes of NADPH-cytochrome P450 reductase and cytochrome P450 LM2 oligomers were 14.8 +/- 1.7 and 19.2 +/- 1.4 nm, respectively. Twenty-four-hour incubation with Emulgen 913 at 4 degrees C at a molar ratio of 1:100 led to the monomerization of NADPH-cytochrome P450 reductase and cytochrome P450 LM2 oligomers, the particle sizes diminishing to 6.1 +/- 1.3 and 5.2 +/- 0.4 nm, respectively. The thermal stability of NADPH cytochrome P450 reductase monomers was the same as that of oligomers, whereas cytochrome P450 LM2 monomers were less thermostable than oligomers and cytochrome P450 in microsomes. Similar to cytochrome P450 LM2 oligomers and the microsomal hemoprotein, cytochrome P450 LM2 monomers formed complexes with type I and II substrates, but with Kd values higher than those of microsomes and cytochrome P450 LM2 oligomers. Kinetic parameters (Vmax and Km) of H2O2- and cumene hydroperoxide-dependent oxidation of benzphetamine and aniline in the presence of cytochrome P450 LM2 oligomers, monomers, and microsomes were determined. Peroxidase activities of the oligomers and monomers were the same, but were lower than those of microsomes. Thus the substitution of protein-protein interactions in cytochrome P450 LM2 oligomers with protein-detergent interactions in the monomers did not influence the catalytic properties of the hemoprotein. PMID- 1416971 TI - Comparative study of monomeric reconstituted and membrane microsomal monooxygenase systems of the rabbit liver. II. Kinetic parameters of reductase and monooxygenase reactions. AB - The kinetic parameters of NADPH-dependent cytochrome P450 LM2 (2B4) reduction and substrate oxidation in the monomeric reconstituted system, consisting of purified NADPH-cytochrome P450 reductase and cytochrome P450 LM2 monomers, and in phenobarbital-induced rabbit liver microsomes were compared. In the absence of benzphetamine, NADPH-dependent reduction of cytochrome P450 LM2 was monophasic in the monomeric reconstituted system and biphasic in the microsomes. The presence of the substrate in the monomeric reconstituted system caused the appearance of the fast phase. In this system substrate-free cytochrome P450 LM2 was entirely low-spin, and the addition of benzphetamine shifted the spin equilibrium to a high state very weakly. No correlation between high-spin content and the proportion of the fast phase of NADPH-dependent LM2 reduction was found in the system. Vmax values for the oxidation of type I substrates (benzphetamine, dimethylaniline, aminopyrine) in the monomeric reconstituted system were higher or the same as in the microsomes, whereas Km values for the substrates and NADPH were lower in the microsomes. Maximal activity of the monomeric reconstituted system was observed at a 1:1 NADPH-cytochrome P450 reductase/cytochrome P450 LM2 ratio. Measurements of benzphetamine oxidation as a function of NADPH-cytochrome P450 reductase/cytochrome P450 LM2 ratio at a constant total protein concentration allowed the Kd of the NADPH-cytochrome P450 reductase/cytochrome P450 LM2 complex to be estimated as 6.4 +/- 0.5 microM. Complex formation between the NADPH-cytochrome P450 reductase and cytochrome P450 LM2 monomers was not detected by recording the difference binding spectra of the reductase monomers with LM2 monomers or by treatment the mixture of the monomers of the proteins with the crosslinking reagent, water-soluble carbodiimide. PMID- 1416972 TI - Thermal denaturation of plastocyanin: the effect of oxidation state, reductants, and anaerobicity. AB - The thermal stability of plastocyanin (PC) was determined as a function of oxidation state of the copper center and the presence of oxidants, reductants, oxygen, and EDTA. It was found that the copper center and its ligands play a crucial role in maintaining the stability of PC. Thermal denaturation was monitored by using far-uv circular dichroism (CD) spectra to monitor changes in secondary structure, the near-uv CD ellipticity at 280 nm to monitor changes in tertiary structure, and the absorbance at 597 nm and the 255-nm CD transition to monitor changes in the copper center. Reduced PC (Tm = 71 degrees C) was found to be more stable than the oxidized form (Tm = 61 degrees C). The Tm was increased by addition of reductants, removal of oxygen, or addition of EDTA. Two distinct denatured forms (designated D1 and D2) were separated by anion exchange fast protein liquid chromatography. Neither form contained a native copper center. Form D2 retained the characteristic 280-nm CD band but showed an altered far-uv CD spectrum. Its formation was inhibited by the addition of reductants or the removal of oxygen. It could be refolded to form native, Cu-PC upon incubation with copper plus a reductant such as dithionite. These results suggest that its formation involves the reversible oxidation of a group on the PC molecule, possibly a ligand to the copper such as Cys 84 or Met 92. Form D1 occurred in the presence of ferricyanide or at high temperatures in the presence of oxygen. EDTA inhibited its formation. Form D1 lost the 280-nm CD transition and its far-uv CD spectrum was altered. No renaturation was observed suggesting that Form D1 is the product of an irreversible oxidation step possibly involving a histidine ligand to the copper. Forms D1 and D2 are not interconvertible and represent the endpoints of two different denaturation pathways. PMID- 1416973 TI - Characterization of the 4 S polycyclic aromatic hydrocarbon-binding protein in human liver and cells. AB - The 4 S polycyclic aromatic hydrocarbon (PAH)-binding protein (PBP) is a soluble protein that binds PAHs with high affinity in mouse, rat, and rabbit. Until now, this protein had not been detected in human placenta or human cells in culture by cytosol labeling and gradient centrifugation assay. Thanks to a preliminary fractionation of cytosol by sedimentation on sucrose gradient or/and gel permeation chromatography, we found that PBP was present in liver, MCF-7 cell line, and hepatocytes of human. To accurately quantitate PBP binding and determine specific binding parameters, a reduction in the amount of charcoal used to adsorb nonspecifically bound benzo[a]pyrene was required. By saturation analysis, the concentration of specific binding sites for [3H]BP in PBP fraction from human liver was 4.6 pmol/mg of protein compared with 14.7 +/- 1.4 pmol/mg in the same fraction from DBA/2J mouse liver. Kinetic studies analyzed by Scatchard and Woolf plots indicate that human liver and MCF-7 cells contain a low-affinity PBP form: the Kd derived from Woolf plot analysis were 14.2 +/- 1.4 and 26.2 +/- 1.8 nM, respectively. DBA/2J mouse possesses a higher-affinity PBP form, the same analysis indicating a Kd of 6.1 +/- 0.3 nM. These data demonstrate that, by comparison to the mouse liver, a lower-affinity form of PBP is present in reduced concentration in human liver, explaining the impossibility of detecting this protein by sedimentation of human cytosol in sucrose gradient. PMID- 1416974 TI - Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. AB - Peroxynitrite (ONOO-), the reaction product of superoxide (O2-) and nitric oxide (NO), may be a major cytotoxic agent produced during inflammation, sepsis, and ischemia/reperfusion. Bovine Cu,Zn superoxide dismutase reacted with peroxynitrite to form a stable yellow protein-bound adduct identified as nitrotyrosine. The uv-visible spectrum of the peroxynitrite-modified superoxide dismutase was highly pH dependent, exhibiting a peak at 438 nm at alkaline pH that shifts to 356 nm at acidic pH. An equivalent uv-visible spectrum was obtained by Cu,Zn superoxide dismutase treated with tetranitromethane. The Raman spectrum of authentic nitrotyrosine was contained in the spectrum of peroxynitrite-modified Cu,Zn superoxide dismutase. The reaction was specific for peroxynitrite because no significant amounts of nitrotyrosine were formed with nitric oxide (NO), nitrogen dioxide (NO2), nitrite (NO2-), or nitrate (NO3-). Removal of the copper from the Cu,Zn superoxide dismutase prevented formation of nitrotyrosine by peroxynitrite. The mechanism appears to involve peroxynitrite initially reacting with the active site copper to form an intermediate with the reactivity of nitronium ion (NO2+), which then nitrates tyrosine on a second molecule of superoxide dismutase. In the absence of exogenous phenolics, the rate of nitration of tyrosine followed second-order kinetics with respect to Cu,Zn superoxide dismutase concentration, proceeding at a rate of 1.0 +/- 0.1 M-1.s-1. Peroxynitrite-mediated nitration of tyrosine was also observed with the Mn and Fe superoxide dismutases as well as other copper-containing proteins. PMID- 1416975 TI - Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. AB - Superoxide dismutase and Fe3+EDTA catalyzed the nitration by peroxynitrite (ONOO ) of a wide range of phenolics including tyrosine in proteins. Nitration was not mediated by a free radical mechanism because hydroxyl radical scavengers did not reduce either superoxide dismutase or Fe3+EDTA-catalyzed nitration and nitrogen dioxide was not a significant product from either catalyst. Rather, metal ions appear to catalyze the heterolytic cleavage of peroxynitrite to form a nitronium like species (NO2+). The calculated energy for separating peroxynitrous acid into hydroxide ion and nitronium ion is 13 kcal.mol-1 at pH 7.0. Fe3+EDTA catalyzed nitration with an activation energy of 12 kcal.mol-1 at a rate of 5700 M-1.s-1 at 37 degrees C and pH 7.5. The reaction rate of peroxynitrite with bovine Cu,Zn superoxide dismutase was 10(5) M-1.s-1 at low superoxide dismutase concentrations, but the rate of nitration became independent of superoxide dismutase concentration above 10 microM with only 9% of added peroxynitrite yielding nitrophenol. We propose that peroxynitrite anion is more stable in the cis conformation, whereas only a higher energy species in the trans conformation can fit in the active site of Cu,Zn superoxide dismutase. At high superoxide dismutase concentrations, phenolic nitration may be limited by the rate of isomerization from the cis to trans conformations of peroxynitrite as well as by competing pathways for peroxynitrite decomposition. In contrast, Fe3+EDTA appears to react directly with the cis anion, resulting in greater nitration yields. PMID- 1416976 TI - Bactericidal activity of peroxynitrite. AB - Peroxynitrite is a strong oxidant formed by macrophages and potentially by other cells that produce nitric oxide and superoxide. Peroxynitrite was highly bactericidal, killing Escherichia coli in direct proportion to its concentration with an LD50 of 250 microM at 37 degrees C in potassium phosphate, pH 7.4. The apparent bactericidal activity of a given concentration peroxynitrite at acidic pH was less than that at neutral and alkaline pH. However, after taking the rapid pH-dependent decomposition of peroxynitrite into account, the rate of the killing was not significantly different at pH 5 compared to pH 7.4. Metal chelators did not decrease peroxynitrite-mediated killing, indicating that exogenous transition metals were not required for toxicity. The hydroxyl radical scavengers mannitol, ethanol, and benzoate did not significantly affect toxicity while dimethyl sulfoxide enhanced peroxynitrite-mediated killing. Dimethyl sulfoxide is a more efficient hydroxyl radical scavenger than the other three scavengers and increased the formation of nitrogen dioxide from peroxynitrite. In the presence of 100 mM dimethyl sulfoxide, 60.0 +/- 0.3 microM nitrogen dioxide was formed from 250 microM peroxynitrite as compared to 2.0 +/- 0.1 microM in buffer alone. Thus, formation of nitrogen dioxide may have enhanced the toxicity of peroxynitrite decomposing in the presence of dimethyl sulfoxide. PMID- 1416977 TI - Inhibition of organic anion transport in endothelial cells by hydrogen peroxide. AB - ATP loss is a prominent feature of cellular injury induced by oxidants or ischemia. How reduction of cellular ATP levels contributes to lethal injury is still poorly understood. In this study we examined the ability of H2O2 to inhibit in a dose-dependent manner the extrusion of fluorescent organic anions from bovine pulmonary artery endothelial cells. Extrusion of fluorescent organic anions was inhibited by probenecid, suggesting an organic anion transporter was involved. In experiments in which ATP levels in endothelial cells were varied by treatment with different degrees of metabolic inhibition, it was determined that organic anion transport was ATP-dependent. H2O2-induced inhibition of organic anion transport correlated well with the oxidant's effect on cellular ATP levels. Thus H2O2-mediated inhibition of organic anion transport appears to be via depletion of ATP, a required substrate for the transport reaction. Inhibition of organic anion transport directly by probenecid or indirectly by metabolic inhibition with reduction of cellular ATP levels was correlated with similar reductions of short term viability. This supports the hypothesis that inhibition of organic anion transport after oxidant exposure or during ischemia results from depletion of ATP and may significantly contribute to cytotoxicity. PMID- 1416978 TI - Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible expression of aldehyde dehydrogenase in hepatoma cells. AB - The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces the expression of a number of genes. The biochemical process of the induction of aldehyde dehydrogenase (ALDH-3) was investigated in rat H4IIE hepatoma cells in culture. The kinetics of ALDH-3-induction exhibited parallel increases in the rate of transcription, mRNA, protein, and enzyme activity, all reaching a plateau at 36-48 h after addition of TCDD. Half maximal and maximal inductions occurred at 0.1 and 1 nM of TCDD, respectively. No significant changes in the half-life of ALDH-3 mRNA (14 h) were observed in the cells exposed to three different concentrations of TCDD. Other inducers of xenobiotic metabolism, such as 3 methylcholanthrene and beta-naphthoflavone, also induced ALDH-3 mRNA to a similar level as TCDD, whereas antioxidants or electrophiles, such as tert butylhydroquinone and dimethyl fumarate, did not show any induction of ALDH-3 mRNA. To examine the involvement of the aryl hydrocarbon receptor (Ah receptor) in the induction of ALDH-3, mouse variant cell lines defective in cytochrome P450IA1-induction and a parental wild type cell line (Hepa1c1c7) were studied. ALDH-3 mRNA and the transcription of its gene were detected in TCDD-treated wild type cells, but not in the treated and untreated variant cells. These results demonstrate that TCDD induces transcription of the ALDH-3 gene via its binding to the Ah receptor. PMID- 1416979 TI - A reactive nucleophile proximal to vicinal thiols is an evolutionarily conserved feature in the mechanism of Arg aminoacyl-tRNA protein transferase. AB - Aminoacyl-tRNA protein transferases post-translationally aminoacylate protein N termini. At least in part, these enzymes function to allow a subset of cellular proteins to be targeted for protein degradation. A eukaryotic enzyme of this class, Arg aminoacyl-tRNA protein transferase, arginylates N-terminal Glu or Asp residues of proteins, allowing such proteins to be recognized by a specific ubiquitin-protein ligase. We showed previously that inorganic arsenite, a reagent expected to bind specifically to protein vicinal thiol groups, inhibited Arg aminoacyl-tRNA transferase activity in rabbit reticulocyte lysate (N. S. Klemperer and C. M. Pickart, 1989, J. Biol. Chem. 264, 19245-19252). We now report that a bifunctional arsenoxide reagent, p-[(bromoacetyl) amino]phenylarsenoxide, is a potent and irreversible inactivator of the same enzyme (K0.5 = 11.5 microM). Bromoacetyl aniline, which lacks the arsenoxide moiety, has no effect. These results show that the transferase has a reactive nucleophile proximal to the site which binds arsenoxides. The related monofunctional arsenoxide reagent, p-aminophenylarsenoxide, is a reversible inhibitor whose potency (K0.5 = 7.7 microM) is 20-fold greater than that of inorganic arsenite. As expected for a mechanism in which p-aminophenylarsenoxide binds to vicinal thiol groups: (i) pretreatment of reticulocyte lysate with a thiol-blocking reagent prevents binding of the transferase to a phenylarsenoxide Sepharose column; and (ii) inhibition by p-aminophenylarsenoxide is reversed by a competing chemical dithiol, but not by a monothiol reagent. Like the rabbit enzyme, Arg aminoacyl-tRNA protein transferase from the yeast Saccharomyces cerevisiae (expressed in Escherichia coli) is reversibly inhibited by the monofunctional phenylarsenoxide and irreversibly inactivated by the bifunctional phenylarsenoxide (but not by bromoacetylaniline). Thus, a reactive nucleophile proximal to vicinal thiol groups is a conserved feature of the activity of the transferase. We speculate that these groups are catalytic elements in the transferase active site. PMID- 1416980 TI - Expression of the Chlamydomonas reinhardtii chloroplast tRNA(Glu) gene in a homologous in vitro transcription system is independent of upstream promoter elements. AB - Chloroplast tRNA(Glu) is a bifunctional molecule involved in both the early steps of chlorophyll synthesis and chloroplast protein biosynthesis. Recently the enzymes involved in these processes have been characterized from the green alga Chlamydomonas reinhardtii. In order to investigate whether transcription of the gene for the tRNA(Glu) cofactor would be a possible point of regulation for the biosynthesis of chlorophyll, a homologous in vitro transcription system for C. reinhardtii chloroplast RNA polymerase was developed. The enzymatic activity was partially purified by ion-exchange chromatography to separate it from nuclear RNA polymerases. The highest rate of synthesis was found at pH 7.9, 40 mM KCl, 9 mM MgCl2 and with 25 micrograms plasmid DNA containing the chloroplast tRNA gene per milliliter. The activity was not sensitive to high amounts of alpha-amanitin (500 micrograms/ml) and rifampicin, but was clearly inhibited by heparin. This system was used to undertake a promoter analysis of one of the two identical tRNA(Glu) gene copies found in the C. reinhardtii chloroplast genome (trnE1). The analyzed tRNA gene behaved like a single transcription unit driven by its own promoter. The transcript terminated in a run of four consecutive T residues downstream of the gene. The nucleotide sequence in the 5' region of the gene revealed several potential promoter elements with homology to known chloroplast promoters of the " 10 and -35 region" and the "Euglena promoter" types. Surprisingly, deletion of the complete 5' region did not affect in vitro transcription, while partial deletions of the 5' and 3' coding region totally abolished transcription. This indicates the presence of an internal control region previously found for genes transcribed by nuclear RNA polymerase III. Protein binding studies with the coding region of trnE1 using gel retardation assays demonstrated the formation of two differently sized complexes. In vitro transcription of the tRNA(Glu) gene in extracts prepared from light and dark grown algae failed to demonstrate any significant influence of light on the transcription reaction. PMID- 1416981 TI - Inhibition of enoyl-CoA hydratase by long-chain L-3-hydroxyacyl-CoA and its possible effect on fatty acid oxidation. AB - The kinetics of bovine liver enoyl-CoA hydratase (EC 4.2.1.17) or crotonase with 2-trans-hexadecenoyl-CoA as a substrate were studied because different rates were obtained with two assay methods based on measurements of substrate utilization and product formation, respectively. L-3-Hydroxyhexadecanoyl-CoA, the product of the crotonase-catalyzed hydration of 2-trans-hexadecenoyl-CoA, was found to be a strong competitive inhibitor of the enzyme with a Ki of 0.35 microM. In contrast the short-chain product, L-3-hydroxybutyryl-CoA, is a weak competitive inhibitor with a Ki of 37 microM. L-3-Hydroxyhexadecanoyl-CoA is a much stronger inhibitor of crotonase than are other short-chain and long-chain intermediates of beta oxidation and crotonase is more severely inhibited by this compound than are all beta-oxidation enzymes tested so far. Determination of true kinetic parameters for the crotonase-catalyzed hydration of long-chain substrates requires the removal of product in a coupled assay. When this was done, the Km for 2-trans hexadecenoyl-CoA with bovine liver crotonase was found to be only 9 microM. It is suggested that under conditions of restricted beta-oxidation, when 3-hydroxyacyl CoAs accumulate in mitochondria, the inhibition of crotonase by long-chain 3 hydroxyacyl-CoAs may limit the further degradation of medium-chain and short chain intermediates of beta-oxidation. PMID- 1416982 TI - Import of mutant forms of mitochondrial aspartate aminotransferase into isolated mitochondria. AB - To gain some insight into the role played by certain protein domains in the import of mitochondrial aspartate aminotransferase in isolated mitochondria, three protein mutants were constructed by using the plasmid pOTS-mAspAT, which contains the nucleotide sequence encoding for the mature form of this enzyme. Two mutant proteins in which Cys-166 was substituted with either serine or alanine and another protein lacking the nine N-terminal amino acids were all synthesized in a cell-free transcription/translation system. Comparison was made among the newly synthesized mutant proteins and the newly synthesized wild type aspartate aminotransferase with respect to their capability to enter mitochondria. All the mutant proteins proved to be able to enter mitochondria even though with a lower efficiency than the wild type enzyme. Interestingly the thiol reagent mersalyl proved to inhibit import of both wild type enzyme and serine mutant, whereas import of alanine mutant was found to be insensitive to mersalyl, thus showing that Cys-166 is the unique -SH group involved in import. Import of mitochondrial aspartate aminotransferase by mitochondria is shown to involve certain protein domains present in the mature protein, two of them being the Cys-166 and the N terminal regions. PMID- 1416983 TI - Purification of a tumor-specific PNA-binding glycoprotein, gp200, from a human embryonal carcinoma cell line. AB - A 200-kDa peanut agglutinin (PNA)-binding glycoprotein, gp200, has been purified and partially characterized from the human embryonal carcinoma cell line, HT-E (833k). Tissue distribution analysis of this molecule by lectin blotting with PNA of detergent-extracted proteins from human cell lines and tissues demonstrated expression limited to nonseminomatous germ cell tumors. The 200-kDa protein was purified with lectin affinity and gel filtration chromatography. Purification to apparent homogeneity was demonstrated by one- and two-dimensional gel electrophoresis. Characterization of gp200 revealed it to be a surface integral membrane glycoprotein; however, gp200 could also be purified from the culture media of EC cells, suggesting gp200 has an extracellular role. The carbohydrate groups of gp200 are N-linked and partially sialylated and contain terminal galactose residues. These initial studies suggest that the PNA-defined glycoprotein, gp200, is a candidate for a nonseminomatous germ cell tumor marker. PMID- 1416984 TI - Cloning and expression of the bovine cardiac sodium-calcium exchanger. AB - Two clones (p17 and p13), each containing the complete coding sequence for the bovine cardiac Na+/Ca2+ exchanger, were obtained from a lambda gt10 cDNA library by screening with cDNA probes from the canine exchanger. The coding sequence of clone p17 was 92 and 98% identical to the canine cDNA at the nucleotide and amino acid levels, respectively. Nine of the 21 amino acid differences between the two exchangers were found within the 32-amino acid signal sequence. The sequenced portions of the 3' untranslated regions of the cow and dog clones were 88% identical. Na+/Ca2+ exchange activity was expressed in Xenopus laevis oocytes injected with cRNA from clone p17, and in COS cells transfected with expression vectors containing p17. Immunoprecipitation of 35S-labeled proteins from transfected cells with an antibody against the N-terminal portion of the bovine exchanger showed the presence of a 120-kDa protein corresponding to the intact cardiac exchanger. The second bovine clone (p13) did not express exchange activity in either of the above expression systems, presumably because it contained a 300-bp insert with multiple stop codons which interrupted the coding sequence. Comparison of the 5' untranslated regions of p13 and p17 revealed a 156 bp segment in p17 that was apparently spliced out of p13. This segment contained a short open reading frame. A chimera encoding the 5' untranslated region of p13 and the coding sequence of p17 exhibited only a modest (74%) increase in expressed exchange activity in transfected cells compared to p17, suggesting that the presence of the upstream open reading frame in p17 did not greatly reduce translation efficiency. The results suggest that alternate splicing mechanisms may be involved in processing mRNA for the bovine cardiac exchanger. PMID- 1416985 TI - Activation and inhibition of protein kinase C isozymes alpha and beta by Gd3+. AB - Gd3+ was evaluated as a probe for Ca2+ sites on protein kinase C (PKC) by studying its ability to replace Ca2+ in activation of PKC isozymes II (beta) and III (alpha) in the lipid systems phosphatidylserine/1,2-dioleoyl-sn-glycerol (PS/DO) and diheptanoylphosphatidylcholine (PC7)/DO. PKC beta was stimulated by Ca2+ or Gd3+ in PS/DO whereas activity in PC7/DO was independent of these metals. Thus, it is suggested that Gd3+ replaces Ca2+ at a site involving metal-lipid interactions. High concentrations of Ca2+ or Gd3+ inhibited activity in both lipid systems. Analysis of the Gd3+ inhibition in the PC7/DO system suggests that it is due to formation of GdATP, which competes at the MgATP site. Activity of PKC alpha was dependent on low concentrations of Ca2+ in both lipid systems. The ability of Gd3+ to substitute for Ca2+ could not be evaluated in the PS system due to the inability to completely remove contaminating Ca2+ without chelating buffers. Successful reduction of contaminating Ca2+ was achieved in the PC7 system but Gd3+ failed to substitute for Ca2+ in activating PKC alpha and only caused inhibition. This is consistent with binding of Gd3+ to a Ca2+ site at or near the active site of the enzyme rather than to a site on the lipid. These results indicate that interactions between PKC and Gd3+ are complex, involving occupation of more than one class of sites. Conditions for separately evaluating the individual sites can be manipulated by selection of isozyme and lipid system. PMID- 1416986 TI - Purification and characterization of cyanide hydratase from the phytopathogenic fungus Gloeocercospora sorghi. AB - Previous studies have demonstrated that fungal pathogens of cyanogenic plants produce cyanide hydratase (CHT, EC 4.2.1.66), which converts HCN to formamide. Production of CHT in these fungi is thought to be a means of circumventing cyanide toxicity, and CHT is thus believed to be an important pathogenicity trait. In the present study, 13 species of fungi were assayed for CHT production, and all 7 species that were pathogens of sorghum, a cyanogenic plant, produced this enzyme. CHT was purified to apparent homogeneity from one of these sorghum pathogens, Gloeocercospora sorghi. The enzyme had a Km of 12 mM for KCN. Enzymatically functional CHT was obtained only as a large molecular entity of greater than 300 kDa. However, a polypeptide of approximately 45 kDa was identified as the only component of purified CHT detectable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 45-kDa polypeptide band could be resolved into three isozymes of pI 6.1, 6.3, and 6.5. Antibodies raised against the 45-kDa polypeptide inhibited the G. sorghi CHT activity and showed high specificity in Western blots to a polypeptide of approximately the same size. The evidence suggests that functional G. sorghi CHT is an aggregated protein that consists of 45-kDa polypeptides. A CHT with similar properties was also found in the fungus Colletotrichum graminicola, another pathogen of sorghum. PMID- 1416987 TI - Cytoplasmic accumulation of a normally mitochondrial malonyl-CoA decarboxylase by the use of an alternate transcription start site. AB - Malonyl-CoA decarboxylase, a normally mitochondrial enzyme, accumulates in the cytoplasm of specialized glands to cause production of multiple methyl-branched fatty acids. Evidence was presented that a single copy of the decarboxylase gene present in the goose genome codes for both the mitochondrial form found in extremely low amounts in the liver and the cytosolic form found in large amounts in uropygial glands. To elucidate how a single gene encodes both forms, the malonyl-CoA decarboxylase gene and the cDNAs for both the mitochondrial (liver) and the cytoplasmic (gland) species were cloned and sequenced. The decarboxylase gene, found in a 21-kb segment of cloned genomic DNA, is composed of five exons of 0.521, 0.118, 0.156, 0.145, and 1.93 kb interrupted by 6.9, 1.5, 0.45, and 9.3 kb introns. Exon 1 revealed two ATGs in frame 150 bp apart. cDNA for the cytoplasmic form and mitochondrial form showed identical nucleotide sequence, except that the latter was longer than the former. The longest cDNA for the cytoplasmic form of the enzyme extended only 44 bp 5' to the second ATG and the position corresponded to the transcription initiation site of the cytoplasmic form revealed by primer extension and RNase protection. The cDNA for the mitochondrial form isolated from the library extended 19 bp further upstream. Primer extension and RNase protection indicated that transcripts for the mitochondrial form initiated upstream from the first ATG. The N-terminal segment of the open reading frame initiated at the first ATG showed an amphipathic signal sequence appropriate for mitochondrial import. A putative full length mRNA for the mitochondrial form of the enzyme when translated in vitro yielded a 55-kDa primary translation product which was processed by removal of about 5 kDa during uptake into goose liver mitochondria. These results strongly suggest that in most tissues transcription initiates 5'- to the first ATG, generating a transcript that would generate a protein with an N-terminal leader for transport into mitochondria. In the uropygial gland the use of an alternate promoter generates transcripts initiated between the two ATGs and the translation product accumulates in the cytoplasm since it lacks a mitochondrial targeting sequence. PMID- 1416989 TI - Partial purification and characterization of mannitol: mannose 1-oxidoreductase from celeriac (Apium graveolens var. rapaceum) roots. AB - A mannitol:mannose 1-oxidoreductase was isolated from celeriac (Apium graveolens var. rapaceum) root tips by fractionation with (NH4)2SO4, followed by chromatography on a Fractogel DEAE column and then concentration with (NH4)2SO4. This newly discovered mannitol dehydrogenase catalyzes the NAD-dependent oxidation of mannitol to mannose, not mannitol to fructose. The sugar product of the enzyme reaction was identified by three independent HPLC systems and by an enzymatically linked system as being mannose and not fructose or glucose. Normal Michaelis--Menten kinetics were exhibited for both mannitol and NAD with Km values of 72 and 0.26 mM, respectively, at pH 9.0. The Vmax was 40.14 mumol/h/mg protein for mannitol synthesis and 0.8 mumol/h/mg protein for mannose synthesis at pH 9.0. In the polyol oxidizing reaction, the enzyme was very specific for mannitol with a low rate of oxidation of sorbitol. In the reverse reaction, the enzyme was specific for mannose. The enzyme was strongly inhibited by NADH and sensitive to alterations of NAD/NADH ratio. The enzyme is of physiological importance in that it is mainly localized in root tips (sink tissue) where it functions to convert mannitol into hexoses which are utilized to support root growth. Product determination and kinetic characterization were carried out on an enzyme preparation with a specific activity (SA) of 30.44 mumol/h/mg protein. Subsequently, the enzyme was further purified to a SA of 201 mumol/h/mg protein using an NAD affinity column. This paper apparently represents the first evidence of the existence of a mannitol:mannose 1-oxidoreductase and also the first evidence of the presence of a mannitol dehydrogenase in vascular plants. PMID- 1416988 TI - Characterization of the proto-oncogene pim-1: kinase activity and substrate recognition sequence. AB - The human pim-1 proto-oncogene was expressed in Escherichia coli as a glutathione S-transferase (GST)-fusion protein and the enzymatic properties of its kinase activity were characterized. Likewise, a Pim-1 mutant lacking intrinsic kinase activity was constructed by site-directed mutagenesis (Lys67 to Met) and expressed in E. coli. In vitro assays with the mutant Pim-1 kinase showed no contaminating kinase activity. The wild-type Pim-1 kinase-GST fusion protein showed a pH optimum of 7 to 7.5 and optimal activity was observed at either 10 mM MgCl2 or 5 mM MnCl2. Higher cation concentrations were inhibitory, as was the addition of NaCl to the assays. Previous work by this laboratory assaying several proteins and peptides showed histone H1 and the peptide Kemptide to be efficiently phosphorylated by recombinant Pim-1 kinase. Here we examine the substrate sequence specificity of Pim-1 kinase in detail. Comparison of different synthetic peptide substrates showed Pim-1 to have a strong substrate preference for the peptide Lys-Arg-Arg-Ala-Ser*-Gly-Pro with an almost sixfold higher specificity constant kcat/Km over that of the substrate Kemptide (Leu-Arg-Arg-Ala Ser*-Leu-Gly). The presence of basic amino acid residues on the amino terminal side of the target Ser/Thr was shown to be essential for peptide substrate recognition. Furthermore, phosphopeptide analysis of calf thymus histone H1 phosphorylated in vitro by Pim-1 kinase resulted in fragments containing sequences similar to that of the preferred synthetic substrate peptide shown above. Therefore, under optimized in vitro conditions, the substrate recognition sequence for Pim-1 kinase is (Arg/Lys)3-X-Ser/Thr*-X', where X' is likely neither a basic nor a large hydrophobic residue. PMID- 1416990 TI - Sarcolipin, the "proteolipid" of skeletal muscle sarcoplasmic reticulum, is a unique, amphipathic, 31-residue peptide. AB - The sarcoplasmic reticulum of rabbit skeletal muscle contains a small "proteolipid," i.e., a protein which is soluble in acidic CHCl3/CH3OH. We propose the name sarcolipin for this small protein, to signify its lipid-like solubility and association with the sarcoplasmic reticulum. We have determined the following amino acid sequence for sarcolipin, using protein chemistry methods: M E R S T R E L C L N F T V V L I T V I L I W L L V R S Y Q Y. This 31-residue sequence includes a 19-residue hydrophobic segment which probably spans the sarcoplasmic reticulum membrane. The molecular weight calculated from the sequence, 3733, agrees with that measured by fast atom bombardment mass spectrometry, showing that sarcolipin contains no attached fatty acyl or other prosthetic groups. PMID- 1416991 TI - Salt-induced refolding of myoglobin at acidic pH: molecular properties of a partly folded intermediate. AB - The molecular properties of the salt-induced partly folded acidic state of apomyoglobin as well as myoglobin were investigated by fluorescence and circular dichroism of the extrinsic fluorophore 1,8-anilinonaphthalenesulfonate. The occurrence of a fluctuating tertiary structure ("molten globule") at acidic pH in the presence of salt was suggested by the disappearance of the dichroic activity of the fluorophore bound to the partly folded protein. Moreover, the structure of the intermediate is not influenced by the presence of heme, thus suggesting that heme is not crucial in the early stage of myoglobin folding. PMID- 1416992 TI - Characterization of a high affinity octamer transcription factor binding site in the human lipoprotein lipase promoter. AB - A high affinity octamer transcription factor (OTF-1) binding site has been identified and characterized at position--46 base pairs (bp) in the proximal human lipoprotein lipase (LPL) promoter. The affinity of the LPL OTF-1 binding site was approximately 15-fold greater than a consensus octamer sequence, ATTTGCAT, present at position--66 bp in the mouse Vk T1 promoter, and approximately 5-fold greater than the OTF-1 site present at position--49 bp in the human histone H2B promoter. Diethylpyrocarbonate interference assays have identified both 5' and 3' adenine nucleotides, which flank the core LPL ATTTGCAT sequence and interfere with OTF-1 binding when chemically modified. Introduction of mutations in either 5' or 3' flanking AT-rich sequences lowered the affinity of OTF-1 binding below the level observed with the wild-type LPL octamer oligomer. A double mutation in both flanking AT regions, however, greatly reduced the affinity of this site to levels similar to that observed with the mouse Vk T1 OTF site. An additional nuclear transcription factor, NF-Y, has been shown to bind to a functional CCAAT box motif located at -65 bp in the LPL promoter using specific alpha-NF-Y antisera. The observation of high affinity OTF-1 and NF-Y binding sites in a region of the proximal LPL promoter which is necessary for high levels of LPL transcription suggests that these sites with their associated proteins play important functional roles in the transcriptional activation of the LPL promoter during adipocyte differentiation. PMID- 1416993 TI - Lipid peroxidation in Plasmodium falciparum-parasitized human erythrocytes. AB - cis-Parinaric acid (PnA) was used as a fluorescent probe to study lipid peroxidation in nonparasitized and Plasmodium falciparum-parasitized erythrocytes, upon challenge by cumene hydroperoxide and tert-butyl hydroperoxide. Parasitized erythrocytes were less susceptible toward lipid peroxidation than nonparasitized erythrocytes with which they had been cultured. Furthermore, nonparasitized erythrocytes cultured together with parasitized cells, and thereafter isolated on a Percoll gradient, were less susceptible toward lipid peroxidation than erythrocytes kept under the same experimental conditions but in the absence of parasitized cells. We concluded, therefore, that the intracellular development of the parasite leads to an increase in the resistance against oxidative stress, not only of the host cell membrane of the parasitized erythrocyte, but also in the plasma membrane of the neighboring cells. The erythrocyte cytosol of parasitized cells and/or the intraerythrocytic parasite was required for the increased protection of the host cell membrane, since ghosts prepared from parasitized erythrocytes were more susceptible to lipid peroxidation than those prepared from nonparasitized ones. Vitamin E content of parasitized erythrocytes was lower than that of nonparasitized cells. However, parasitized erythrocytes promoted extracellular reduction of ferricyanide at higher rates, which might be indicative of a larger cytosolic reductive capacity. It is suggested that the improved response of intact erythrocytes is due to an increased reduction potential of the host-erythrocyte cytosol. The role of vitamin C as a mediator of this process is discussed. PMID- 1416994 TI - Analysis of the nucleoside moiety of cobalamin and cobalamin analogues using gas chromatography-mass spectrometry. AB - Existing techniques for identification of cobalamin and cobalamin analogues generally use the intact molecule during characterization with somewhat ambiguous results. In this study a method is described for the identification of the nucleoside in the lower axial ligand of cobalamin and a variety of naturally occurring cobalamin analogues that differ from cobalamin in the base that is present in the nucleoside. Cobalamin and cobalamin analogues were isolated from biological samples by affinity chromatography using R-protein-Sepharose columns. The nucleosides of the lower axial ligand were then hydrolyzed and isolated by column chromatography using a mixed bed column. Nucleosides were oxidized with periodate and reduced with borohydride. After reisolation, the t butyldimethylsilyl derivatives were prepared and analyzed using gas chromatography/mass spectrometry with selected ion monitoring. A stable isotope internal standard of cobalamin was biosynthetically produced and used to quantitate cobalamin in rabbit kidney. Cobalamin analogues were also shown to be present in rabbit kidney, but they contain the 5,6-dimethylbenzimidazole nucleoside (alpha-ribazole) in the lower axial ligand, indicating that these analogues differ from cobalamin in the corrin ring region of the molecule. PMID- 1416995 TI - Identification of Tyr115 labeled by S-(4-bromo-2,3-dioxobutyl)glutathione in the hydrophobic substrate binding site of glutathione S-transferase, isoenzyme 3-3. AB - Incubation of S-(4-bromo-2,3-dioxobutyl)glutathione (S-BDB-G), a reactive analogue of glutathione, with the 3-3 isoenzyme of rat liver glutathione S transferase at pH 6.5 and 25 degrees C results in a time-dependent inactivation of the enzyme. The kobs exhibits a nonlinear dependence on S-BDB-G concentration from 50 to 900 microM, with a kmax of 0.073 min-1 and KI = 120 microM. The addition of 5 mM S-hexylglutathione, a competitive inhibitor with respect to glutathione, completely protects against inactivation by S-BDB-G. About 2.0 mol of [3H]S-BDB-G/mol of enzyme subunit is incorporated concomitant with 100% inactivation, whereas only 0.96 mol of reagent/mol subunit is incorporated in the presence of S-hexylglutathione when activity is fully retained. Modified enzyme, prepared by incubating glutathione S-transferase with [3H]S-BDB-G in the absence or in the presence of S-hexylglutathione, was reduced with NaBH4, reacted with N ethylmaleimide, and digested with trypsin. Analysis of the tryptic digests, fractionated by reverse-phase high-performance liquid chromatography, revealed Tyr115 as the amino acid whose reaction with S-BDB-G correlates with inactivation. Examination of the stability of S-(4-bromo-2,3 dioxobutyl)glutathione and modified enzyme in the absence and presence of dithiothreitol and under acidic conditions suggests that for stable linkage to peptides, the carbonyl moieties of the reagent should be reduced immediately after modification of a protein. Comparison of results from the 4-4 and 3-3 isoenzymes of rat liver glutathione S-transferase (both of the mu gene class) indicates: the 4-4 isoenzyme exhibits a greater affinity for S-BDB-G; Cys86 is labeled by [3H]S-BDB-G in both isoenzymes but is nonessential for activity; in the 3-3 isoenzyme, Cys86 is more accessible to S-BDB-G; and Tyr115 is an important residue in the hydrophobic binding site of both enzymes. PMID- 1416996 TI - Vibrational circular dichroism studies of epidermal growth factor and basic fibroblast growth factor. AB - Vibrational circular dichroism (VCD) studies are reported for two unrelated recombinant growth factor proteins: epidermal growth factor and basic fibroblast growth factor (bFGF). NMR, electronic CD, and bFGF X-ray studies indicate that these two proteins are primarily composed of beta-sheet and loop secondary structure elements with no detectable alpha-helices. Two reports on solution conformation of these proteins using FTIR absorption spectroscopy with subsequent resolution enhancement confirmed the presence of a large fraction of a beta-sheet conformation but in addition indicated the presence of large absorption bands in the 1650-1656 cm-1 region, which are typically assigned to alpha-helices. The VCD spectra of both proteins have band shapes that strongly resemble those of other high beta-sheet fraction proteins, such as the trypsin family of proteins. Quantitative analysis of the VCD spectra also indicates that these proteins are predominantly in beta-sheet and extended ("other") conformations with very little alpha-helix fraction. These results agree with the CD interpretation and affirm that the FTIR peaks in the region 1650-1656 cm-1 can be assigned to loops. This study provides an example of the limitations of using FTIR frequencies alone for examination of protein secondary structure. PMID- 1416997 TI - Subunit interactions of Rubisco activase: polyethylene glycol promotes self association, stimulates ATPase and activation activities, and enhances interactions with Rubisco. AB - The effect of polyethylene glycol (PEG) on the enzymatic and physical properties of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activase was examined. In the presence of PEG, Rubisco activase exhibited higher ATPase and Rubisco activating activities, concomitant with increased apparent affinity for ATP and Rubisco. Specific ATPase activity, which was dependent on Rubisco activase concentration, was also higher in the presence of Ficoll, polyvinylpyrrolidone, and bovine serum albumin. The ability of Rubisco activase to facilitate dissociation of the tight-binding inhibitor 2-carboxyarabinitol 1 phosphate from carbamylated Rubisco was also enhanced in the presence of PEG. Mixing experiments with Rubisco activase from two different sources showed that tobacco Rubisco activase, which exhibited little activation of spinach Rubisco by itself, was inhibitory when included with spinach Rubisco activase. Polyethylene glycol improved the ability of tobacco and a mixture of tobacco plus spinach Rubisco activase to activate spinach Rubisco. Estimates based on rate zonal sedimentation and gel-filtration chromatography indicated that the apparent molecular mass of Rubisco activase was two- to fourfold higher in the presence of PEG. The increase in apparent molecular mass was consistent with the propensity of solvent-excluding reagents like PEG to promote self-association of proteins. Likewise, the change in enzymatic properties of Rubisco activase in the presence of PEG and the dependence of specific activity on protein concentration resembled changes that often accompany self-association. For Rubisco activase, high concentrations of protein in the chloroplast stroma would provide an environment conducive to self-association and cause expression of properties that would enhance its ability to function efficiently in vivo. PMID- 1416998 TI - Cytochrome P450cam-catalyzed oxidation of a hypersensitive radical probe. AB - trans-1-Phenyl-2-vinylcyclopropane, a hypersensitive radical probe, is oxidized by cytochrome P450cam (CYP101) to a diastereomeric mixture of the corresponding epoxide (81%), (trans-2-phenylcyclopropyl)acetaldehyde (6%), and trans-5-phenyl-2 penten-1,5-diol (13%). trans-5-Phenyl-2-penten-1-ol and (trans-2 phenylcyclopropyl)ethane-1,2-diol are not detectably formed. Authentic standards of all the products have been synthesized and used to establish the identities (or the absence) of the metabolites. Studies with [18O]H2O demonstrate that the oxygens at positions 1 and 5 in the rearranged diol derive from molecular oxygen and water, respectively. Catalytic turnover of the enzyme is required for product formation from the olefin, but incubation of the epoxide metabolite with the enzyme, or with buffer alone, yields both the aldehyde and the rearranged diol products. The absence of trans-5-phenyl-2-penten-1-ol implies that the lifetime of the putative radical intermediate is so short that its existence as a discrete entity is questionable. A cationic intermediate is unlikely but cannot be excluded because the same metabolites are formed in a secondary reaction, even at pH 8.0, from the epoxide. The results provide no evidence for the involvement of radicals or cations in the epoxidation reaction, in agreement with results on the oxidation of olefins in organic solvents by metalloporphyrin catalysts. PMID- 1416999 TI - Conformation inversion of bilirubin formed by reduction of the biliverdin-human serum albumin complex: evidence from circular dichroism. AB - As shown by circular dichroism spectroscopy, biliverdin preferentially adopts an M-helicity conformation on human serum albumin in aqueous buffer, pH 7.5, whereas biliverdin exhibits only a weak preference for the P-helicity conformation on bovine serum albumin at the same pH. Upon rapid reduction of the complexes with sodium borohydride, P-helicity bilirubin-IX alpha is obtained on the human albumin complex, and M-helicity bilirubin-IX alpha is obtained on the bovine serum albumin complex. Thus, biliverdin in effect undergoes an inversion of chirality upon reduction. Since the reduction did not afford a rubin with the same helicity as that of the verdin, the observations point to a hitherto undetected conformational mobility of albumin-bound bilirubin. PMID- 1417000 TI - Effect of dexamethasone and phenobarbital on run-on transcription rate and CYP3A mRNA concentration in rat liver: changes during development. AB - Modulation of CYP3A1 and CYP3A2 mRNA expression by dexamethasone and by phenobarbital has been studied in immature (21-day-old) and adult (90-day-old) rat liver. Positive modulation of these forms by both agents markedly declines with the age of the animals. However, CYP3A2 mRNA, although physiologically extinguished in the adult females, still responds to dexamethasone stimulation. The regulatory mechanisms underlying the differential behavior of CYP3A1 in the immature and adult animals have been further investigated by analyzing the early changes in the run-on transcription rates and the subsequent mRNA accumulation in the liver in response to the inducer agents. CYP3A genomic clones were constructed and characterized for this purpose. The use of a unique cosCYP/3A1 intronic sequence, identified in this work, made possible the selective determination of the transcription rate of this gene by run-on assay, as a function of ontological development and inducer treatment. Parallel determination of the mRNA concentration in the liver by dot blot analysis demonstrated that dexamethasone induces CYP3A1 essentially through transcription regulation in immature animals, while in adults it is suggested to act mainly at a post transcriptional level. PMID- 1417001 TI - 15gag proteinase of myeloblastosis-associated virus: specificity studies with substrate-based inhibitors. AB - The specificity of the proteinase of myeloblastosis-associated virus (MAV) was studied with (a) 21 substrate-based inhibitors, (b) 9 inhibitors with pseudopalindrome sequences, (c) 8 chimeric inhibitors, and (d) 3 compounds designed as human immunodeficiency virus 1 (HIV-1) proteinase inhibitors. The central inhibitory unit (transition state or cleaved bond analog) and the role of the inhibitor side chains from P4 to P4' were investigated. MAV proteinase prefers an aromatic side chain in P1 and a small aliphatic nonpolar chain in P2 and P2'. Residues in P5 and P4 positions are outside of the short catalytic cleft of the enzyme, but still influence binding considerably. The data obtained provide evidence that the MAV proteinase has generally lower specificity and poorer binding than the HIV proteinase. PMID- 1417002 TI - High pressure gel-permeation assay for the proteolysis of human aggrecan by human stromelysin-1: kinetic constants for aggrecan hydrolysis. AB - The adaptation of an analytical procedure for aggrecan based upon gel-permeation chromatography to an FPLC-based protocol has significantly sped up the analysis. The faster assay has permitted determination of the kinetic constants for digestion of human aggrecan by human stromelysin-1. Monomeric aggrecan appeared to be hydrolyzed by stromelysin-1 to multiple forms with lower molecular weight. The disappearance of high-molecular-weight aggrecan was first-order, showing Km much larger than 2 microM and kc/Km = 4000 M-1 s-1 at pH 7.5. The disappearance of high-molecular-weight aggrecan upon hydrolysis by stromelysin-1 at pH 5.5 was also first-order, with kc/Km = 10,700 M-1 s-1. The disappearance of high molecular-weight aggrecan at pH 7.5 was first-order for digestion by human leukocyte elastase with kc/Km = 230,000 M-1 s-1, by human cathepsin G with kc/Km = 4200 M-1 S-1, and by human plasma plasmin with kc/Km = 2800 M-1 s-1, all with Km much larger than 2 microM. PMID- 1417003 TI - [Reappraisal of Zelen's method in randomized controlled trials]. AB - This paper discusses Zelen's method (a study design with pre-randomization) in randomized controlled trials from the following aspects: 1) compliance of patients with a randomly assigned treatment; 2) infringement of patients' right to choose treatments; and 3) unfairness that only patients assigned to a new treatment are allowed a choice of treatments. The reason Zelen's method is rarely used in the United States or European countries seems to be the lower compliance of treatments in Zelen's method than in the conventional design of randomized controlled trials. Considering the present study practice in Japan, where study subjects are not completely informed by randomized assignment of treatments, Zelen's method is thought to be more practical, and not inferior to the conventional design in terms of compliance. PMID- 1417004 TI - [Screening for ovarian cancer]. AB - In recent years, ovarian cancer has been increasing in Japan. However, a mass screening system for ovarian cancer is not yet established. For this reason, detection of early ovarian cancer is very difficult. 1. Due to the low frequency of ovarian cancer detection, a mass-screening system is not cost-effective. 2. There is no accurate method for the detection of ovarian cancer, as with cytology or colposcopy for the detection of uterine cancer. We describe some methods for the detection of ovarian cancer by mass screening, and point out some problems. Tumor marker is not always useful because of its low sensitivity for early ovarian cancer. It is most important to determine whether or not an ovarian tumor is present. We attempted to detect ovarian tumors at the time of uterine cancer mass screening by ultrasonography (transvaginal proof). Three early ovarian cancers were detected in 10,294 women. PMID- 1417005 TI - [Clinical usefulness of tumor markers for the diagnosis of ovarian cancer]. AB - The most useful diagnostic methods for ovarian cancer at present are diagnostic imaging and measurement of tumor markers. Although many tumor markers have been measured to detect patients with ovarian cancer, the values of diagnostic efficiency are not so high when a single tumor marker is assessed. Therefore, the use of a combination of tumor markers might be expected to yield a higher value. In this study, tumor markers were measured to select an ovarian cancer group from a group in which ovarian tumor was palpable by the pelvic examination. We selected CA 602 from core-protein related markers, CA 54/61 from sugar chain core related markers, and galactosyltransferase associated with tumor (GAT) for their combined use from among eleven markers examined. As a result, the combined use of each two markers or of all three markers appeared to be beneficial to discriminate ovarian cancers from benign ovarian tumors. The combination of all three markers gave a somewhat higher positive rate and diagnostic efficiency value than that of the two markers. The role of tumor markers in the future screening of ovarian cancer was also discussed in this paper. PMID- 1417006 TI - [Radical surgery for ovarian cancer]. AB - Mortality rate of ovarian cancer is increasing in Japan and the management of advanced cases is an important issue in order to improve long term survival. Radical surgery including systematic lymphadenectomy (LNX) from paraaortic nodes through pelvic nodes was, therefore, performed in our department with regular surgery (TAH, BSO, omentectomy) and lymph node metastasis (LNM) was analyses. LNM rate of patients whose LNX done in the primary surgery according to pTNM classification was as follows: pT1: 9.7%, pT2: 1.1%, pT3: 66.7% and that of those LNX done at SLO was as follows: pT1: 8.3%, pT2: 0%, pT3: 69.2%. Since radical surgery improved prognosis of advanced ovarian cancer significantly radical surgery including LNX are strongly recommended as a treatment of advanced ovarian cancer. PMID- 1417007 TI - [Experimental study of biochemical modulation of 5-fluorouracil with l-leucovorin against human esophageal cancer]. AB - Potentiation of cytotoxic effects of 5-fluorouracil (5-FU) were investigated by simultaneous or sequential combination of l-leucovorin (LV) against human esophageal cancer cell line (TE-1, TE-2) and 23 human clinical cancer samples in vitro. LV enhanced the cytotoxic effects of 5-FU on human esophageal cancer cell line as a dose dependent manner, and increased the cytotoxic effect of 5-FU about 1.5-fold with 10 microM and about 2-fold with 100 microM. The incubation time did not affect the effects. The potentiation with LV was also demonstrated against human clinical cancer samples, and the cytotoxic effects of 5-FU increased 7.6% in esophageal cancer, 20.9% in gastric cancer and 25.5% in colorectal cancer. As a result, the potentiating effects of LV against 5-FU seemed to be limited on human esophageal cancer. PMID- 1417008 TI - [Phase I clinical study of combined cisplatin and carboplatin therapy in lung cancer]. AB - A phase I clinical study (a dose escalation test) of combined cisplatin (CDDP) + carboplatin (CBDCA) therapy was carried out in patients with primary or secondary lung cancer (PS 0-2) who had given prior informed consent to the study. The dose level of CDDP was set at 80 mg/m2, while five dose levels (200, 250, 300, 350, 400 mg/m2) of CBDCA were used. Three patients were allocated to each CBDCA dose group. Blood samples were taken immediately before and 0.5, 1, 2, 4, 6 and 24 hours after injection, and were examined for total Pt and free Pt level. The maximum tolerated dose (MTD) was CDDP 80 mg/m2 + CBDCA 400 mg/m2. Thrombocytopenia and leukopenia served as dose limiting factors (DLF). Total Pt and free Pt levels in blood after this combined therapy were higher than those after treatment with CDDP alone. The results from this study suggest that CDDP 80 mg/m2 + CBDCA 350 mg/m2 would be a suitable dose for phase II study of this combined chemotherapy. A multi-center pilot study based on these findings is now under way. PMID- 1417009 TI - [Aminoglutethimide and aminoglutethimide+tamoxifen treatment for advanced breast cancer]. AB - Twenty-eight and 24 patients with advanced breast cancer were treated with Aminoglutethimide (AG) or AG + Tamoxifen (AG + TAM) from June 1984 to June 1989, respectively. Evaluated cases were 25 and 21 treated with AG or AG+TAM, respectively. Objective response was seen in 5/25 (20.0%) for AG treatment with 9, 13, 16, 20 and 31 months remission and 4/21 (19.1%) for AG + TAM treatment with 6, 7, 12 and 26 months remission. Response rate according to dominant site of metastases were 1/10 in soft tissue, 2/7 in bone, 2/7 in lung and pleura treated with AG, 1/9 in soft tissue, and 3/5 in lung treated with AG + TAM treatment. Two of the 5 responding patients in AG treatment group had prior tamoxifen treatment and 3 out of 4 responding patients in AG + TAM treatment group had prior chemoendocrine therapy with tamoxifen and FAC chemotherapy. Main toxic side effects were lethargy and/or rash, and drug discontinuation was required in 3 cases of AG treatment group and 2 cases of AG + TAM treatment group. Serial determination of serum hormone levels during AG or AG + TAM treatment revealed a decrease in estrone and an increase in androstenedione in many cases of both treatment groups. This data suggested that AG treatment may be favorable for endocrine treatment for advanced breast cancer patients, but the response to AG was not augmented by adding TAM. PMID- 1417011 TI - [Endoscopic analysis of gastric mucosal lesions in patients with adult T-cell leukemia during chemotherapy]. AB - Gastric mucosal lesions in 13 patients with adult T-cell leukemia (ATL) were endoscopically studied at least at 2 occasions during chemotherapy for these patients. X-ray examinations by using barium meal showed deformities in 10 patients and abnormal mucosal pattern in 11 out of 13 patients with ATL. The endoscopic examinations revealed gastric ulcers in 5 patients, erosion in 8, diffuse bleeding in 2, tumorous mucosal folds in one, and submucosal tumor in one patient. In 9 out of 12 ATL patients, pathological study revealed that ATL cells had invaded the mucosal area of the stomach. The ulcers and erosions were improved by chemotherapy in 3 out of 5 and 5 out of 8 patients, respectively, whereas the erosion was not reduced in 2 and even aggravated in one patient. Interestingly, the gastric lesions formed by ATL cell invasion were improved by the administration of anticancer agents in 5 out of 9 patients. However, these lesions reappeared together with systemic lesions of ATL. PMID- 1417010 TI - [Multicenter cooperative study of pre- and post-operative adjuvant chemotherapy in the treatment of colorectal cancer. North Kyushu Co-operative Study Group for Cancer Chemotherapy]. AB - The usefulness of pre- and post-operative adjuvant chemotherapy in colorectal cancer patients was studied by the North Kyushu Co-operative Study Group for Cancer Chemotherapy (21 participating institutions). Comparisons were made among group I given a tegafur suppository preoperatively+tegafur oral preparation postoperatively, group II given a tegafur suppository preoperatively+UFT oral preparation postoperatively and group III given a tegafur oral preparation postoperatively. No differences were seen in the incidence of postoperative complications depending on whether or not tegafur suppositories were administered preoperatively. There were also no differences in the symptom or incidence of side effects due to postoperative administration of tegafur or UFT. In a study of 5-FU concentration in the lymph nodes due to preoperative tegafur administration and recurrences, the concentration of 5-FU was significantly higher in the lymph nodes of cases without recurrences than in those with recurrences, and it was suggested that a relation exists between the concentration of agent and recurrences. The concentration of 5-FU in the lymph nodes of Dukes B patients was significantly higher in cases without recurrences than in those with recurrences. The non-recurrence rate (healthy rate) was better in the group given UFT postoperatively than in that administered tegafur postoperatively although the difference was not significant. PMID- 1417012 TI - [THP-adriamycin-based combination chemotherapy in the treatment of non-Hodgkin's lymphoma]. AB - Thirty patients with non-Hodgkin's lymphoma were treated with THP-adriamycin based combination chemotherapy. Complete remission was obtained in eighteen (72%) of 25 evaluable patients. Nine of 18 patients are still alive in complete remission lasting 9 to 34 months (median 24 mo). Severe side effects such as bone marrow suppression, gastrointestinal symptoms and cardiotoxicity were rare. It was concluded that THP-adriamycin-based combination chemotherapy is relatively mild and safe, so this regimen is useful for elderly patients or patients with complications. PMID- 1417013 TI - [Anti-emetic effect and safety of single dose of ondansetron injection in double blind comparison study with placebo]. AB - In order to make an objective evaluation of anti-emetic effect, safety and usefulness of ondansetron injection in nausea and vomiting associated with cancer chemotherapy, we carried out a double-blind placebo controlled comparative study in patients receiving high-single dose (50 mg/m2 or more) of cisplatin. Either 4 mg of ondansetron or saline injection was given intravenously at 15 min. before administration of cisplatin. If anti-emetic effect of the test drug was insufficient, an additional dose of 4mg of ondansetron was given intravenously, as the rescue medication. Ondansetron was significantly superior to placebo in anti-emetic effect (p < 0.001). Efficacy rates were 66.7% (22/33 cases) in ondansetron and 20.0% (6/30 cases) in placebo groups. Seven and 21 cases required rescue medication with 4 mg single intravenous dose of ondansetron due to insufficiency of anti-emetic effect, in ondansetron group and placebo group, respectively. Thus the number of patients who required rescue medication was obviously greater in placebo group than that in ondansetron group. The rates of inhibitory effect of rescue medication on nausea and emesis were 14.3% (1/7 cases) in ondansetron group and 61.9% (13/21 cases) in placebo group. Side effects were observed in 1 case (eruption) in ondansetron group and in 2 cases (headache, diarrhoea; 1 case each) in placebo group. Furthermore, fever developed in 1 case in placebo group after the rescue medication. Elevation of total bilirubin value was observed in 2 cases in ondansetron group and 1 case in placebo group, however, these changes were mild and did not pose noteworthy clinical problem. From these results, ondansetron was shown to possess an excellent anti-emetic effect on nausea and emesis induced by highly emetogenic anti-cancer drugs, such as cisplatin, and to have no problem in safety, and thus it was considered to be a useful anti-emetic agent. PMID- 1417014 TI - [Anti-emetic effect and safety of ondansetron tablet in double-blind comparison with placebo]. AB - Ondansetron, a selective 5-HT3 receptor antagonist, has already been reported to have a marked effect to alleviate or prevent nausea and vomiting associated with cancer chemotherapy, after its intravenous administration. The present study was planned to examine the usefulness of its tablet form, which was prepared for the convenient use in outpatients receiving chemotherapy. In order to make an objective evaluation of anti-emetic effect and safety of ondansetron 4 mg tablet, this study was conducted in double-blind comparison versus placebo in patients receiving cisplatin at a single dose of 50mg/m2 or higher. Either 4 mg of ondansetron or placebo (lactose tablet) was administered orally once at 2 hrs prior to administration of cisplatin. If any satisfactory anti-emetic effects were not obtained, 4 mg of ondansetron injection was given once intravenously as a rescue medication. The inhibitory effect on nausea and vomiting was assessed in 4 grades as "excellent", "good", "fair" and "poor" based on severity of nausea and number of vomiting that occurred during the first 24hrs after administration of cisplatin. When rescue medication was conducted, the case was assessed as "poor". Ondansetron was significantly superior to placebo in inhibition of nausea and vomiting, in which efficacy rates (excellent+good) of ondansetron and placebo groups were 58.1% (25/43 cases) and 16.7% (7/42 cases), respectively. Number of cases requiring rescue medication with ondansetron injection was obviously greater in placebo group (31 cases) than that in ondansetron group (12 cases). In those patients given ondansetron injection as the rescue medication, satisfactory effects were obtained in 5 cases in ondansetron group and in 18 cases in placebo group. Although side effects including chest itching (ondansetron group), headache and dull headache (placebo group) were observed after the rescue medication with ondansetron injection, these symptoms were not severe and disappeared after 1-2 days. As mentioned above, ondansetron tablet was shown to possess excellent anti-emetic effect on nausea and emesis induced by high dose of cisplatin and to have no problem in safety. Hence ondansetron was proven to be clinically very useful anti-emetic. PMID- 1417015 TI - [Evaluation of SN-307 (ondansetron), given intravenously in the treatment of nausea and vomiting caused by anticancer drugs including cisplatin--a placebo controlled, double-blind comparative study]. AB - Clinical usefulness of ondansetron as an antiemetic for the treatment of nausea and vomiting induced by anticancer drugs including cisplatin (> or = 50 mg/m2) was evaluated by a multi-institutional, double-blind comparative study with placebo with inpatients with various malignancies. In this study, efficacy, safety and usefulness of single dose of ondansetron (4 mg) or placebo (physiological saline), given intravenously for initial nausea and vomiting were observed for 24 hours after treatment. Clinically, very effective or effective response was seen in 64% (16/25) of the group O (ondansetron) and 5.9% (1/17) of the group P (placebo). No clinically significant adverse effects or abnormal laboratory test values were reported in the group of O. Diarrhea (1 case) and the elevation of laboratory test values (GOT.GPT, T-bilirubin, LDH, in 3 cases) were reported in the group of P. General safety assessment was considered "safe" in 100% of both group O and group P, and there was no statistical difference between two groups. Usefulness was considered as "useful" in 64% (16/25) of group O and 6.3% (1/16) of group P, and O was significantly better than group P (p < 0.001) level. In conclusion, ondansetron provides a safe and effective antiemetic measure when employed therapeutically against nausea and vomiting induced by regimens including cisplatin. PMID- 1417016 TI - [Studies of clinical usefulness of new tumor markers of ovarian cancer, CA 54/61 and CA 602--CA 602 assay reagent kit, performance its normal value and correlations with other tumor markers]. AB - We made a preclinical study of a newly developed tumor maker, CA 602, and its clinical study using serum samples available from 58 institutions located throughout Japan. In the preclinical study, a CA 602 assay kit was investigated for the reproducibility and precision of assay results; and in the clinical study, the kit was investigated for the normal value of the marker, for variations in assay result with age, menstrual cycle and term of pregnancy, and for correlations of assay results with those of other tumor markers. The tests of the kit for simultaneous reproducibility and interval reproducibility of assay results, and the results of analytical recovery and dilution tests were all favorable; the kit proved to be reliable in both precision and reproducibility. For the study, 2 cutoff levels were set: mean + 2 SD of healthy subjects, i.e., 63 U/ml, and the level which permits the maximal efficiency of differential diagnosis of benign from malignant ovarian tumors, i.e., 90 U/ml. The assay results showed that CA 602 levels were low in women aged 50 and over; the levels were high in the first half of pregnancy, and also high in the menstrual period to the early follicular phase. The assay results of CA 602 also proved to be intimately correlated with those of CA 125, which suggested that the 2 markers might be analogous to each other. CA 602 proving to be of high reproducibility even in the range of concentrations below the cutoff value, the measurement with the marker appeared to be of high precision, capable of detecting even the slightest variations in the antigen. CA 602 therefore appears of great value in the early detection of recurrent ovarian cancers. PMID- 1417017 TI - [Sharp decline in plasma CEA and reduction of liver metastasis after UFT administration in a patient with recurrent gastric cancer]. AB - Carcinoembryonic antigen (CEA) in plasma is useful for the detection of recurrent colonic or gastric cancer and the monitoring of plasma in patients with recurrent cancer displaying therapeutic effect. We report a sharp decline of CEA in a patient with recurrent gastric cancer by 6 months oral administration of UFT. The patient was an 81-year-old male who had undergone gastrectomy for advanced gastric cancer. Eight months post-operatively, the plasma CEA began to rise logarithmically, and recurrent tumor in the remnant stomach and liver metastasis were detected by fibergastroscope (FGS) and abdominal CT. After administration of UFT at a dose of 300 mg per day, CEA abruptly declined logarithmically and normalized in 6 months. Presently marked reduction of recurrent foci and metastases were found by FGS and abdominal CT. Therefore sequential changes in plasma CEA in this patient can be considered to reflect the effect of therapy for recurrent gastric cancer by UFT. PMID- 1417018 TI - [Successful treatment of adenocarcinoma of the lung with bone metastases by combined chemotherapy with epirubicin, mitomycin C and carboplatin]. AB - A 62-year-old male was admitted with lumbago and gait disturbance for 3 months. He had complained of a cough for 3 years. His admission chest radiography revealed tumor shadow in right lower lung field. The patient was diagnosed as adenocarcinoma of the lung by transbronchial biopsy. Bone scintigraphy revealed multiple bone metastases with rib, lumbar and pelvic bone. Clinical staging was IV and performance status was 3. The patient was treated by combined chemotherapy with epirubicin 20 mg/m2, mitomycin C 8 mg/m2 and carboplatin 350 mg/m2. After 2 cycles he was able to walk by himself and the lung tumor regressed in 40% of pretreated size. This combined chemotherapy could be performed for outpatients because of the mild gastrointestinal side effects and little hydration. PMID- 1417019 TI - Perifolliculitis capitis abscedens et suffodiens. Resolution with combination therapy. PMID- 1417020 TI - Comparison of the carcinogenic potential of trioxsalen bath PUVA and oral methoxsalen PUVA. A preliminary report. AB - BACKGROUND AND DESIGN: There is an increasing concern about the long-term carcinogenic effect of oral psoralen with long-wave UV radiation in the A range (PUVA). Most follow-up investigations indicate a definite risk of squamous cell carcinoma of the skin with long-term PUVA treatment. In a recently published study of 4799 Swedish patients who had received PUVA, it was noted that 833 patients who had received trioxsalen bath or oral trioxsalen did not show any increased risk of skin cancer in contrast to oral methoxsalen. This finding has been further investigated in this study. We compared four dermatologic university clinics in Sweden with regard to the carcinogenic potential of the PUVA regimen used. One clinic used trioxsalen bath PUVA exclusively and the other three used oral methoxsalen. Information on their PUVA-treated patients was collected and linked with information from the Swedish Cancer Registry to identify individuals with squamous cell carcinoma of the skin. RESULTS: A total of 18 squamous cell carcinomas of the skin were reported in 2975 PUVA-treated patients until 1987. The expected number was 3.1. The center using bath PUVA only had no increased risk of squamous cell carcinoma of the skin in contrast to the three centers using oral methoxsalen-PUVA. The increased risk for male subjects from those centers varied from six to 13 times that in the general population, but for female subjects a significant increased relative risk was found only at one center. CONCLUSION: In this preliminary report, PUVA treatment with trioxsalen bath seems to be less carcinogenic than the oral dosage. However, differences in the patient populations might also have affected the outcome of the study. More information on this field is needed. PMID- 1417021 TI - Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls. AB - BACKGROUND AND DESIGN: Increases in sebaceous gland activity are often the earliest sign of the approach of puberty in children. These increases have been attributed to increases in the secretion of adrenal androgens, but the supporting data are sparse and are based on measurements of urinary, rather than serum, androgen concentrations. In this study, we examined sebum composition, serum levels of dehydroepiandrosterone sulfate, and pubertal stage in 111 boys and girls, aged 2 to 15 years. Sebum composition was evaluated by measuring the ratio of wax esters/(cholesterol + cholesterol esters), a ratio known to increase with increasing sebaceous gland activity. RESULTS: Both wax esters/(cholesterol + cholesterol esters) ratios and serum dehydroepiandrosterone sulfate levels began to increase in children 7 to 10 years old. These changes occurred in many children before the appearance of any physical signs of puberty. Wax esters/(cholesterol + cholesterol esters) ratios were correlated with dehydroepiandrosterone sulfate levels in both boys and girls. In prepubertal children, the regression lines passed through the origin. In subjects who were in early or late puberty, the y intercepts of the regression lines had positive values. CONCLUSION: Adrenal androgens appear to be the major determinants of sebaceous gland activity during the prepubertal period and to be additive to another hormone or hormones during puberty. PMID- 1417022 TI - Loose anagen hair as a cause of hereditary hair loss in children. AB - BACKGROUND AND DESIGN: The loose anagen hair syndrome is a recently described disorder with enhanced hair loss in which anagen hairs can be painlessly pulled from the scalp. RESULTS: In three families, we have observed an autosomal dominant form of inheritance. We have confirmed that the extracted bulbs consist only of cortical cells and that the hair shafts have an abnormal shape. Using routine light and electron microscopy, we observed disadhesion between all layers of the follicle and within some layers and premature keratinization of the inner root sheath of the follicle. In addition, abnormal maturation of the various layers was observed at the electron microscopic level, including regions of the cortex that contained decreased numbers of filaments. The disorder appears to be cyclic, since relatively normal and markedly affected regions of the shaft can be observed within a single follicle. CONCLUSIONS: Possible mechanisms responsible for the disease include abnormal intercellular signaling and disturbances of desmosomal components and/or cadherins. PMID- 1417023 TI - A double-blind comparison of adhesive bandages with the use of uniform suction blister wounds. AB - BACKGROUND AND DESIGN: The assessment of cutaneous wound healing in humans has been hampered by the inability to evaluate multiple wounds with identical origins, treatment histories, and sizes. There have been no double-blind wound healing studies in humans that compared one wound dressing with another. The purpose of this study was to determine if identical suction blister wounds could serve as a model to evaluate and compare wound healing and overall cosmetic appearance of wounds treated with commercially available adhesive bandages. In a double-blind study, we compared superficial skin wounds of identical depth and diameter, created on the forearms of five human subjects by means of a suction blister device. The wounds were covered by two common, commercially available adhesive bandages or a copolymer of polyurethane membrane type of wound dressing. We compared the degree of reepithelialization, erythema, skin depression, and overall cosmetic appearance of wounds with respect to the specific adhesive bandages used. RESULTS: The wounds covered with the copolymer of polyurethane membrane were judged to have better overall appearance and advanced reepithelialization compared with identical wounds covered by the other wound dressings. With the use of x5 magnification for viewing the wounds on the final day of evaluation (between days 18 and 22), the wounds treated with the copolymer of polyurethane membrane were judged to be the least depressed wounds in fields of identical wounds in the three subjects studied. Concordance between the evaluators' "blinded" assessments was uniform, and no discrepancy between the evaluators' assessments occurred at any of the time points. CONCLUSION: Identical wounds created with a suction blistering device can be used reliably to detect differences between the performances of wound dressings in healing superficial wounds. Superficial cutaneous wounds covered with a copolymer of polyurethane dressing demonstrated a superior rate of reepithelialization, less depression, and a better overall cosmetic appearance than wounds covered with two commercially available adhesive bandages. PMID- 1417024 TI - Dermatitis as a presenting sign of cystic fibrosis. AB - BACKGROUND: Three percent to 13% of patients with cystic fibrosis present with protein-energy malnutrition that is characterized by hypoproteinemia, edema, and anemia and is associated with high morbidity and mortality. Cutaneous manifestations of malnutrition are rare in patients with cystic fibrosis and have been attributed to deficiencies of protein, zinc, and essential fatty acids. OBSERVATIONS: We describe five patients who presented with failure to thrive, hypoproteinemia, edema, and a cutaneous eruption before the onset of pulmonary symptoms and before the diagnosis of cystic fibrosis was made. The rash had a predilection for the extremities (lower > upper), perineum, and periorificial surfaces. In most cases, erythematous, scaling papules developed by 4 months of age and progressed within 1 to 3 months to extensive, desquamating plaques. Alopecia was variable, and mucous membrane or nail involvement was not observed. The rash was associated with malnutrition and resolved in all survivors within 10 days of providing pancreatic enzyme and nutritional supplementation. The pathogenesis of the rash is unclear, but it appears to stem from deficiencies of zinc, protein, and essential fatty acids and may be mediated by alterations in prostaglandin metabolism. CONCLUSIONS: Cystic fibrosis should be included in the differential diagnosis of the red, scaly infant, particularly when failure to thrive, hypoproteinemia, and edema are also present. Recognition of rash as a sign of cystic fibrosis complicated by protein-energy malnutrition will allow earlier diagnosis and treatment of these patients and may improve their outcome. PMID- 1417025 TI - Iontophoresis of vinblastine into normal skin and for treatment of Kaposi's sarcoma in human immunodeficiency virus-positive patients. The Military Medical Consortium for Applied Retroviral Research. AB - BACKGROUND: Patients who test positive for human immunodeficiency virus type 1 (HIV-1) and who have disfiguring and/or painful cutaneous lesions of Kaposi's sarcoma (KS) may not be candidates for systemic chemotherapy and/or immunotherapy. Intralesional vinblastine sulfate, as a single-agent chemotherapeutic drug, has been used with some success to treat KS in patients who are HIV-1 positive. However, some patients may not tolerate the pain associated with injection of vinblastine. Transcutaneous iontophoresis of vinblastine was evaluated for therapy of KS in HIV-1-infected patients. Prior to therapy of patients, we iontophoresed vinblastine into the normal skin of volunteers who were not infected with HIV-1 to document the clinical and histologic features that occurred. OBSERVATIONS: Iontophoresis produced a localized erythematous papular eruption in non-HIV-infected volunteers but not in HIV-1-infected patients. Histologic changes in the biopsy specimens taken from non-HIV-infected volunteers consisted primarily of scattered necrotic keratinocytes and a mild to moderate superficial lymphohistiocytic infiltrate. Thirty-one lesions of KS were treated with partial to complete clearing and symptomatic improvement. CONCLUSION: Clinical and histologic features of iontophoresed normal skin suggest an immunologic mechanism of action. Iontophoresis of vinblastine for KS is well tolerated and results in symptomatic improvement as well as varying degrees of clearing of the lesions. PMID- 1417026 TI - Hydantoin-induced cutaneous pseudolymphoma with clinical, pathologic, and immunologic aspects of Sezary syndrome. AB - BACKGROUND: The phenytoin-induced hypersensitivity syndrome is characterized by the development of fever, rash, lymphadenopathy, and hepatitis associated with leukocytosis and eosinophilia. This article describes the unusual occurrence of a pseudo-Sezary syndrome in the days following the introduction of phenytoin treatment. OBSERVATION: A phenytoin-induced erythroderma developed in a 60-year old woman the histologic, cytologic, and immunologic characteristics of an erythrodermal cutaneous T-cell lymphoma of the Sezary syndrome type with lymph node involvement. The dramatic improvement after withdrawal of drug therapy and the absence of recurrence 5 years after led us to consider it as a hydantoin induced pseudolymphoma. CONCLUSIONS: Although lymph node pseudolymphomas induced by phenytoin are well known, few cases of hydantoin-induced mycosis fungoides have been reported in the literature. We present herein the first case of a Sezary-like syndrome associated with phenytoin therapy. Such a patient must be monitored regularly because of the risk of a true malignant lymphoma developing even many years later. PMID- 1417027 TI - Papular umbilicated granuloma annulare. A report of four pediatric cases. AB - BACKGROUND: Granuloma annulare is a common skin condition usually presenting as annular plaques composed of intradermal papules. Variants such as disseminated, subcutaneous, and perforating have been described. In this article, the clinical and histologic features of a distinct papular umbilicated form of granuloma annulare are described. OBSERVATIONS: Four boys aged 5 to 9 years presented with papular, umbilicated, flesh-colored papules limited to the dorsa of the hands and fingers. Histologically there were unusually distributed but typical features of granuloma annulare, including well-demarcated areas of necrobiosis of collagen, localized beneath areas of epidermal thinning and parakeratosis. There was no perforation. CONCLUSIONS: Papular umbilicated granuloma annulare appears to be a distinct variant that may be difficult to diagnose because of its unique clinical and histologic features. PMID- 1417028 TI - Cutaneous findings in craniofacial malformation syndromes. AB - BACKGROUND: A number of craniofacial malformation syndromes are characterized by prominent abnormalities of the skin, hair, nails, and mucous membranes. Many of these findings have been discussed little or not at all in the dermatologic literature. The goal of this review is to present some of the more prominent and distinctive syndromes to increase their recognition by dermatologists and to stimulate further investigation. OBSERVATIONS: The literature regarding syndromes in which major craniofacial anomalies, eg, craniosynostosis or clefting, were present was reviewed and those syndromes with prominent mucocutaneous findings were identified. Although some are well described in the literature, the findings in others are insufficiently detailed from a dermatologic point of view. Little has been written regarding therapeutic intervention. CONCLUSIONS: More accurate descriptions of many craniofacial malformation syndromes are needed by dermatologists. Alerting the dermatologic community to their existence should stimulate attempts at therapeutic intervention on behalf of affected persons. PMID- 1417029 TI - Flushing reactions in the cancer chemotherapy patient. The lists are longer but the strategies are the same. PMID- 1417030 TI - Dermatitis and nutritional deficiency. Diagnostic and therapeutic considerations. PMID- 1417031 TI - Erythematous, vesicular lesions in a newborn. Incontinentia pigmenti. PMID- 1417032 TI - Rubbery zosteriform nodules on the back. Nevus lipomatosus cutaneous superficialis (Hoffmann-Zurhelle). PMID- 1417033 TI - Multiple facial, neck, and upper trunk papules in a black child. Childhood granulomatous perioral dermatitis with involvement of the neck and upper trunk. PMID- 1417034 TI - A nodule on the side of the neck in a child. Branchial cleft cyst. PMID- 1417035 TI - The mismatched match. PMID- 1417036 TI - Immunofluorescence findings in lichen planopilaris: a contrasting experience. PMID- 1417037 TI - A photonumeric scale for the assessment of cutaneous photodamage. PMID- 1417038 TI - Molluscum contagiosum and human immunodeficiency virus. PMID- 1417039 TI - Doxorubicin-associated facial flushing. PMID- 1417040 TI - Primary systemic pustular vasculitis with severe intestinal involvement. PMID- 1417041 TI - Livedo vasculitis with protein C system deficiency. PMID- 1417042 TI - Combined acral and flexural reticulate pigmentary anomaly. PMID- 1417043 TI - Systemic interferon gamma as adjuvant therapy for refractory anogenital warts: a randomized clinical trial and meta-analysis of the available data. PMID- 1417044 TI - The radiological dating of injuries. PMID- 1417045 TI - Fungal skin infections. PMID- 1417046 TI - Paediatric outpatient utilisation in a district general hospital. AB - Paediatric outpatient utilisation in a district general hospital was studied for 20 general practices that covered a population of 26,433 children. The actions taken by paediatric staff were analysed for 487 new referrals and 2784 review attendances (the latter in 1630 children) over an eight month period. New referral rates from different general practices varied between 3.7 per thousand children 0 to 15 years and 29.6 with a mean of 13.7, equivalent to 19 per thousand per year. (The national mean based on health district populations is 21.2 per year.) A total of 63% of new referrals and 49% of review patients were aged under 5 years. Over the study period 2.2% of children under 5 years in the population were referred as a new patient, equivalent to 3.1% per year, and 1.3% of children aged 0 to 15 years were referred, equivalent to 1.8% per year. Review attendances on one or more occasion occurred in 6.5% of children under 5 years over the study period, equivalent to 9.2% per year, and for age 0 to 15 years, 4.8% attended once or more times over the study period, equivalent to 6.7% per year. The review attendance rate per thousand child population per practice varied between 59 and 160 with a mean of 81.9. New patients formed 14.8% of the total attendances (the national mean is 18.3%). Review attendance rates were significantly lower when the general practice was large. Socioeconomic factors suggested by a high proportion of children in the general practice list were associated with a high review attendance rate. Altogether 27.0% of new referrals were seen once only and 32.8% had no tests done. The most common reason for attendance was asthma (11% of new and 19% of review patients). The second commonest was for fits (8.4% of new referrals and 4.7% of review patient attendances). PMID- 1417047 TI - Audit of screening for congenital hypothyroidism. AB - The effectiveness and efficiency of the screening programme for congenital hypothyroidism in the Mersey region from 1983 to 1989 was examined by an analysis of laboratory, manual and computerised district records, case notes, and Hospital Activity Analysis data. Births from 1 January 1983 to 31 December 1989 formed the study cohort and the proportion of live births screened, age when treatment was started, validity of the screening test, and the outcome of treatment were determined. In nine out of 10 districts coverage of the neonatal population by the screening programme was incomplete and there was failure to follow up infants who had not been screened. The sensitivity of the test was 97% and the specificity was 99.9%. In 10% of the positive cases treatment was delayed beyond 21 days, the latest was 26 days. It is concluded that administrative deficiencies were predominantly responsible for the inefficiencies of the screening programme. The long term follow up of diagnosed cases should become part of the monitoring process. PMID- 1417049 TI - What do parents know about vitamins? AB - Parents of 120 children attending child health clinics answered a questionnaire on their understanding of vitamins. Fifty four children (45%) were taking vitamins; 12 (22%) were given the wrong dose. Only 19 parents (35%) knew when to stop supplements and 25 (46%) did not realise overdosage was potentially harmful. Only six children (11%) were receiving professional supervision. This indicates a need to improve parental understanding and professional supervision. PMID- 1417048 TI - How much nebulised budesonide reaches infants and toddlers? AB - The amount of budesonide suspension actually delivered to six subjects (aged 4-30 months) by a jet nebuliser and spacer system (System 22) was determined. Two nebulisations were performed in each subject using a filter at the exhalation outlet of the inhalation chamber. An inhalation filter was additionally attached between the facemask and the spacer in the first test. The drug was inhaled during the second test. The nebuliser equipment was washed with ethanol and the amount of drug deposited was determined. The amount of budesonide deposited in the exhalation filter increased when the inhalation filter was omitted. Only 14% of the nominal dose (500 micrograms) of budesonide was found in the inhalation filter, increasing from nine to 19% with increasing age. Approximately 75% of the nominal dose was found in the nebuliser equipment. These findings must be considered when deciding the nominal dose of budesonide suspension to be given to infants and toddlers. PMID- 1417050 TI - Effect of taurine supplementation on fat and energy absorption in cystic fibrosis. AB - In 10 children with cystic fibrosis and persisting steatorrhoea, supplementation with taurine (30-40 mg/kg/day) was given for two months as an adjunct to the usual pancreatic enzyme treatment. A three day fat and energy balance was performed in patients with cystic fibrosis, before and after the supplementation, and in seven healthy controls who did not receive taurine. Faecal fat was measured by a gravimetric method and stool energy was determined using a bomb calorimeter. Patients with cystic fibrosis, before and after taurine, and healthy controls received the same fat and energy intake (calculated by a dietitian). In patients with cystic fibrosis taurine did not produce any improvement of steatorrhoea (mean (SD) faecal fat 8.7 (3.3) v 11.2 (7.0) g/day, respectively before and after the supplementation), of faecal energy loss (0.978 (0.468) v 1.133 (0.539) MJ/day), of faecal fat expressed as percent of fat intake (13.4 (5.6) v 15.1 (9.8)%), and of faecal energy expressed as percent of energy intake (9.9 (3.6) v 11.2 (5.7)%). Healthy controls had significant lower fat (3.5 (2.3) g/day) and energy 0.576 (0.355) MJ/day faecal losses. In conclusion, taurine failed to decrease significantly fat and energy losses. Our study does not support the use of taurine supplementation in the nutritional management of cystic fibrosis. PMID- 1417051 TI - The value of serum IgG titres against Pseudomonas aeruginosa in the management of early pseudomonal infection in cystic fibrosis. AB - We report the results of a clinical trial. Patients enrolled had serum IgG titres against Pseudomonas aeruginosa above the control range. Assignment to the observation or treatment group was by minimisation. Significant signs or symptoms in any patient prompted antipseudomonal treatment. In addition, the treatment group received antipseudomonal treatment at intervals of four months until the serum IgG titre returned to the control range. P aeruginosa was isolated intermittently from patients in the main trial. Nineteen patients were enrolled (12 observation, seven treatment). After one year in the trial changes in parameters studied, including forced expiratory volume in one second, IgG titre, serum IgG concentrations, and frequency of P aeruginosa isolation had improved in the treated group and worsened in the observation group. PMID- 1417052 TI - Management of hypertensive emergencies. AB - Between 1975 and 1985, 454 patients with hypertension were admitted to the Renal Unit of the Hospital for Sick Children. A total of 110 (24%) patients presented with severely raised blood pressures deemed to require emergency management. At presentation 84/110 had symptoms and signs of long standing hypertension with neurological involvement. Between 1975 and 1980 bolus intravenous injections of diazoxide and/or hydralazine were used with the aim of reducing the blood pressure to within the normal range for age in the first 12-24 hours after admission. Of 57 patients treated in this way 13 developed hypotensive complications and four, whose blood pressures returned to normal within 24 hours of admission, suffered irreversible neurological damage. Subsequently, the management changed to the use of intravenous infusions of labetalol (1-3 mg/kg/hour) and/or sodium nitroprusside (0.5-8 micrograms/kg/min) to enable a more gradual controlled reduction of blood pressure over the first 96 hours of admission. Between 1980 and 1985, 53 patients were treated using this regimen. In all cases blood pressure reduction was achieved in a more controlled manner without further neurological impairment or serious irreversible side effects. From our experience, the use of labetalol and sodium nitroprusside by incremental infusion in the critical early phase of management has resulted in improved control of accelerated hypertension without the sudden hypotensive episodes seen when bolus injections are used. PMID- 1417053 TI - Early thrombocytopenia in HIV infection. AB - Three children aged between 7 months and 2 years developed thrombocytopenia as an early feature of HIV infection. The prevalence of this condition, possible pathogenesis, and options for treatment are discussed. HIV testing should be considered in the investigation of a child with thrombocytopenia. PMID- 1417054 TI - Policies for control of communicable disease in day care centres. AB - A survey was carried out to identify the availability and quality of guidelines for the prevention and control of communicable disease and procedures in use in child day care centres within the South West Thames Regional Health Authority. A sample of 50 day care centres was investigated including those funded by social services and privately funded day care centres. Policies for the prevention and control of communicable disease for children and staff showed a wide variation between different centres. Exclusion criteria were unclear especially in relation to carriers of the hepatitis B virus and HIV positive children. Channels for reporting and seeking advice were inconsistent. It is recommended that clear and up to date written guidelines on the prevention and control of communicable diseases should be available in all day care centres with clear indications of good practice and channels for reporting and advice. It is desirable that guidelines are agreed by the different health and local authorities throughout the region. PMID- 1417055 TI - Endocrine deficit after fractionated total body irradiation. AB - Endocrine function was assessed in 31 children (17 boys) after fractionated total body irradiation used in the preparative regimen for bone marrow transplantation. Endocrine dysfunction was present in 25 children. Fifteen of 29 had growth hormone insufficiency 0.9-4.9 years after total body irradiation, yet only three of the 15 had received previous cranial irradiation. Five of 30 had thyroid dysfunction: two with a low thyroxine and raised thyroid stimulating hormone (TSH) concentration and three with a raised TSH and normal thyroxine concentration. Thus the incidence of thyroid dysfunction (16%) is much lower than that reported after single fraction total body irradiation (39-59%). In only two children were abnormalities of the hypothalamic-pituitary-adrenal axis demonstrated. The majority of pubertal children assessed (n = 15) showed evidence of gonadal damage. All the pubertal girls (n = 5) had ovarian failure, although there was evidence of recovery of ovarian function in one girl. All seven boys in late puberty showed evidence of damage to the germinal epithelium, and two of three in early puberty had raised follicle stimulating hormone concentrations. Despite the use of a fractionated total body irradiation regimen, endocrine morbidity is substantial and children undergoing such procedures will require long term endocrine review and management. PMID- 1417056 TI - Toxic shock-like syndrome caused by adenovirus infection. AB - Adenovirus infections commonly occur in childhood and produce a wide range of clinical disease. The most common sites of infection are the respiratory and gastrointestinal tracts but involvement of cardiovascular, neurological, cutaneous, ophthalmic, renal, and hepatic systems can also occur. A case of toxic shock-like syndrome with symptoms of multiorgan involvement resulting from adenovirus infection is reported. PMID- 1417057 TI - Avoiding chemotherapy related late effects in children with curable tumours. PMID- 1417058 TI - Inpatient psychiatry units. PMID- 1417059 TI - Liver transplantation. PMID- 1417061 TI - Desmopressin for bedwetting. PMID- 1417060 TI - Hearing impairment after bacterial meningitis: a review. PMID- 1417062 TI - Desmopressin for bedwetting. PMID- 1417063 TI - Comparison of BCG vaccination at birth and at third month of life. PMID- 1417064 TI - Immunohistochemical localization of basic fibroblast growth factor in wound healing sites of mouse skin. AB - The immunohistochemical localization of basic fibroblast growth factor (bFGF) was examined during wound healing in mouse skin. Frozen sections taken from the rounded skin defects were reacted with polyclonal anti-human recombinant bFGF IgG followed by incubation with FITC-conjugated IgG. The basal layer keratinocytes and hair bulbs at the wound edge were strongly stained with this antibody. In the reepithelized area, several layers of keratinocytes from the basal layer were positively stained regardless of the time after wounding. These findings suggest that germinative keratinocytes which express bFGF function as leading cells in the covering of the wound defect. However, dermal granulation tissue, including capillary endothelial cells, fibroblasts and macrophages unexpectedly did not demonstrate any immunoreactivity throughout the process of wound healing. Simultaneous histochemical investigation using cultivated mouse keratinocytes and bovine aortic endothelial cells showed primarily cytoplasmic fluorescence. The discrepancy in the staining patterns of endothelial cells in vivo and in vitro suggests that immunoreactive bFGF is either not expressed in vivo, or is processed or masked. PMID- 1417065 TI - Congenital ichthyosis with hypogonadism and growth retardation--a new syndrome with peculiar ultrastructural features. AB - A male patient presented with a congenital ichthyosis clinically characterized by generalized erythroderma, fine scaling on the trunk and palmoplantar hyperkeratoses with severely affected nails. The acanthotic epidermis was characterized by hyperproliferation with a large quantity of mitoses and extremely suppressed keratinization without a normal granular layer. The horny layer was parakeratotic and contained remnants of cell debris and lipid droplets. Ultrastructurally the prickle cell layer was characterized by binuclear cells, oedematization of the keratinocytes and isolated dyskeratotic cells. Some suprabasal cells showed unusual morphological features, containing nuclei with cytoplasmic pseudoinclusions, sometimes leading to a complete disintegration of the nuclear structure, and bowl- and lens-shaped accumulations of a filamentous material. Instead of normal tonofibrils, the aggregated material consisted of fine interlacing filaments. The latter are compared with the filamentous shells in ichthyosis hystrix Curth-Macklin and congenital reticular ichthyosiform erythroderma. The clinical symptomatology--congenital ichthyosis, growth retardation, secondary hypogonadism, hepatomegaly--and the ultrastructural characteristics of the keratinization disorder indicate that the present case cannot be considered as a subtype of the recessively inherited ichthyosis congenita group, but suggest a new syndrome as a separate nosologic entity. PMID- 1417066 TI - Human cutaneous leishmaniasis: in-vitro parasite--mononuclear cell interactions in immune and naive individuals. AB - The aim of this study was to compare the ability of Leishmania parasites to survive in mononuclear cells from immune individuals with their ability to survive in cells from naive individuals. For this purpose we established an in vitro system based on the co-culture in suspension of human peripheral blood leukocytes derived from immune and naive subjects and L. major promastigotes. The proportion of monocytes containing intracellular parasites and the number of amastigotes per 100 infected monocytes (parasite burden) were determined 24 and 72 h after in-vitro infection. The proportion of infected cells from naive individuals did not change, and the number of amastigotes either did not change or increased by 1.2 to 1.7-fold between 24 and 72 h incubation. In contrast, in the immune subjects, the proportion of infected monocytes 24 h after infection was lower than in the naive individuals, and a 30-90% decrease in both the proportion of infected monocytes and the parasite burden was observed after 72 h incubation. Based on these results, three characteristics of leishmanicidal activity of mononuclear cells from immune individuals were determined: (a) the proportion of infected monocytes 24 h after infection was lower than 22%; (b) there was a decrease of more than 30% in the proportion of infected monocytes between 24 and 72 h after infection; and (c) there was a significant decrease in the number of amastigotes between 24 and 72 h after infection. The results of this study demonstrate an enhanced leishmanicidal activity of mononuclear cells from immune individuals. PMID- 1417067 TI - Cutaneous drug reactions. An attempt to quantitative estimation. AB - The drugs taken by patients with suspected cutaneous drug reactions (CDR) were recorded during a 4-year period at Sahlgren Hospital in Gotenburg in a prospective study. A total of 440 patients were included. By dividing the frequency of occurrence of the recorded drugs by the number of sold defined daily doses (SDDD) for the city during the same period of time, figures for the CDR risk for different drugs corrected for frequency of use were obtained. The risk of CDR seemed to be highest for gold compounds, trimethoprim with and without sulphonamides, cephalosporins and penicillins. The most common types of CDR were macular and mucalopapular eruptions, followed by urticaria and cutaneous vasculitis. The results correlate well with those of the Boston Collaborative Drug Surveillance Program. PMID- 1417068 TI - Influence of fish oil supplementation on the minimal erythema dose in humans. AB - A previous study using the hairless mouse model demonstrated that diets containing a fish-oil lipid source, which contained high levels of omega-3 fatty acids, markedly increased the minimum erythema dose (MED) when compared with diets containing other polyunsaturated fatty acids. To determine whether fish oil supplementation could produce a similar effect in humans, 20 subjects were randomized into two groups, a placebo group and a group receiving fish-oil supplements over a 4-week period. Results showed a small, but statistically significant, increase in MED in patients whose diet was supplemented with fish oil. Cholesterol and prostaglandin E2 levels were unchanged, while triglyceride levels were significantly decreased in the fish oil group. No significant changes in any of these parameters occurred in the placebo group. PMID- 1417071 TI - Measurement of S phase duration in human epidermis using cyclin immunostaining and 3H-thymidine pulse labelling. AB - Cyclin/PCNA (proliferating cell nuclear antigen) is a nuclear protein strongly associated with DNA replication sites. Under methanol fixation, cyclin immunostaining might serve as a specific marker for S-phase cells. Associated with single labelling with 3H-thymidine, this immunodetection represents an easy method for measuring S-phase duration. Its application to six samples of normal human epidermis allowed us to measure an S phase of 9.7 +/- 0.3 h, a result in fair agreement with a previous estimate of 10.2 h obtained from a classical double-labelling technique with two different concentrations of 3H-thymidine. PMID- 1417069 TI - Etretinate or cyclosporin-A treatment normalizes the enhanced respiratory burst of polymorphonuclear leukocytes in psoriasis. AB - During a therapeutic trial to treat psoriasis with either etretinate or cyclosporin A (CyA) we measured the respiratory burst activity of polymorphonuclear leukocytes (PMN). Six patients received 0.5-0.75 mg/kg etretinate and 14 patients 2.5-5.0 mg/kg CyA over a period of 10 weeks. The extent of psoriasis was graded by the psoriasis area-and-severity index (PASI score). The respiratory burst of PMN isolated from the peripheral blood was measured employing luminol-enhanced chemiluminescence at weeks 0, 3 and 10 and compared with that of 26 healthy control individuals. PMN were stimulated with zymosan particles, aggregated immunoglobulin (aggIg) and concanavalin A (ConA). Both treatment regimens improved psoriasis; at 10 weeks there was an approximate 40% PASI score reduction under etretinate and an 80% improvement under CyA. Before treatment the respiratory burst was abnormally high under stimulation with the three stimuli in patients (p = 0.021 to less than 0.0001). After 3 to 10 weeks PMN activity normalized in all patients and even tended to drop below values correlating with an improvement in skin lesions. We conclude that the elevated respiratory burst of PMN in psoriasis normalizes under treatment with both etretinate and CyA. PMID- 1417070 TI - Induction and repair of UVB-induced cyclobutane pyrimidine dimers and (6-4) photoproducts in organ-cultured normal human skin. AB - To examine the induction and repair of UV-induced DNA damage, indirect immunofluorescence was performed on UVB-irradiated organ-cultured normal human skin using monoclonal antibodies specific for either cyclobutane pyrimidine dimers or (6-4) photoproducts. Nuclear immunofluorescence of cyclobutane pyrimidine dimers and (6-4) photoproducts were observed in a dose-dependent manner after UVB irradiation. The intensity of nuclear immunofluorescence of the upper epidermal layers was stronger and clearer than that of the lower epidermal layers. DNA repair time-course studies showed that both types of DNA damage could be repaired within 24 h after UVB irradiation. PMID- 1417072 TI - Ultrastructural localization of actin in normal human skin. AB - Normal human skin was embedded in Lowicryl K4M. Actin microfilaments were localized by applying a postembedding immunogold technique using the monoclonal anti-actin antibody HHF35. Actin microfilaments are part of the cytoskeleton in muscle and nonmuscle cells. Together with myosin they produce contraction. The antibody labelled myofilaments in smooth muscle arrector pili cells, myoepithelial cells and pericytes. In sweat gland cells the microvilli system, a zone beneath the cytoplasma membrane corresponding to the adhesion belt region, and apocrine decapitation formations showed labelling. PMID- 1417073 TI - Identification of a cell layer containing alpha-smooth muscle actin in the connective tissue sheath of human anagen hair. AB - Immunohistochemical and immunoelectron microscopy studies revealed the presence of alpha-smooth muscle (alpha-SM) actin in fibroblasts located in the connective tissue sheath (CTS) of human anagen hair follicles. Immunostaining was positive from the base of the bulb to the upper part of the lower portion of the mature anagen hair follicles. The late catagen hair follicles did not stain. Ultrastructurally, alpha-SM actin was detected only in the fibroblasts located in the innermost layer of the transverse collagenous fibres. Since alpha-SM actin is located in cells with contractile potential, this newly identified layer may play an important role in the morphological changes of the lower portion of the hair follicle during the hair growth cycle. PMID- 1417074 TI - "Networking" and psychiatric nursing. PMID- 1417075 TI - A practicum in private practice for graduate students in psychiatric nursing. AB - Clinical placements in psychotherapy for graduate students in psychiatric nursing are getting difficult to find because of bureaucracy, liability issues, competition, and safety and convenience concerns in urban areas. One solution is to design a placement in private practice. PMID- 1417076 TI - Borderline omnipotence in pathological gambling. AB - Borderline omnipotence in pathological gambling is examined, including psychodynamics of omnipotence, a theory of the client's use of omnipotence in pathological gambling, and the effects of omnipotence on the treatment and recovery of the pathological gambler. Assessment, staff education, and the need for individualized treatment for the pathological gambler are discussed. PMID- 1417077 TI - Gender issues and borderline personality disorder: why do females dominate the diagnosis? AB - There are significantly more females with the diagnosis of borderline personality disorder than males. This article explores the developmental factors that place females at a greater risk to develop the disorder. Societal expectations that increase the emerging of borderline symptoms are also discussed. Gender differences of "normal" behavior that effect the assigning of the diagnosis are explained. The theory that borderline personality disorder has become the "virus" of psychiatry is presented. PMID- 1417078 TI - Masochism: implications for psychiatric nursing. AB - Psychiatric nurses often encounter patients who seem to be victims of negative circumstances and are unable to reverse these situations. This article explores the phenomenon of masochism as an outcome of the fear of separation or abandonment. A unified theory is presented, and a case is used to demonstrate the theory. PMID- 1417079 TI - Pathological infatuation or the Blue Angel syndrome. AB - The term masochism has undergone an evaluation since first being introduced solely in relation to sexual perversion by Kraft Ebing in 1906. Masochism can be defined as any behavior that is repetitively self destructive. Relationships in which partners sacrifice themselves and their own best interests can be considered masochistic. There is a difference between a normal pattern of falling in love and a masochistic pattern. The concept of pathological infatuation or what this author has termed the Blue Angel syndrome is presented. A case history with clinical examples is examined to further illustrate these concepts. PMID- 1417080 TI - Subspecialization within psychiatric consultation-liaison nursing. AB - Specialization within health care is evolving in response to the proliferation of knowledge about disease treatment and health management. The practice of psychiatric consultation-liaison nursing in the acute care hospital is diversifying through subspecialization as a result of this trend. This article examines the concept of subspecialization within psychiatric consultation-liaison nursing practice. Subspecialization is presented as a safeguard for professional viability and as a hallmark of quality consumer care. Specialization has advantages and potential disadvantages for nursing practice. Strategies are described that maximize the benefits and minimize the disadvantages of subspecialization. PMID- 1417081 TI - Psychic loss in adult survivors of father-daughter incest. AB - Studies show that adult survivors of childhood incest comprise a significant percentage of female psychiatric patients. The varied and multidetermined presenting symptomatology of these patients frequently leads to misdiagnosis and treatment interventions that fail to address core issues of the incest experience. One such issue is the child's experience of the psychic loss of a physically present parent that is part of the emotional trauma of incest. The goal of this paper is to discuss psychic loss as a core element of the incest experience, particularly in father-daughter incest, and to describe the conditions of childhood mourning that inhibit successful resolution of this loss. Attention is addressed to the psychoanalytic understanding of mourning as a basis for interventions in the treatment of adult survivors. PMID- 1417082 TI - Female sexual abuse survivors as patients: avoiding retraumatization. AB - The literature on adult female psychiatric patients who are survivors of childhood sexual abuse is reviewed. This literature shows both high rates of such abuse and a characteristic pattern of symptoms that distinguishes these survivors from other patients. A theoretical framework is discussed which explains how psychiatric symptoms may develop after childhood sexual abuse and how diagnosis and treatment may serve to maintain or intensify such symptoms. Viewing patients from a posttraumatic treatment perspective is advocated as a strategy for nursing to effectively help these patients with the healing process. PMID- 1417083 TI - Re: Review of Agnes Hatfield's Family education in mental illness, Archives of Psychiatric Nursing, February 1992. PMID- 1417084 TI - Clinical significance of mucin production in post-irradiated cervical carcinoma. AB - Histological sections from 50 patients with clinical stage Ib to stage IIb squamous cell carcinoma of the cervix, initially treated by radiotherapy and followed by Wertheim hysterectomy, were reviewed and stained for mucin. The tissues from 17 (34%) of the patients contained no residual carcinoma. Mucin production was demonstrated in tumour tissue from 18 (55%) of the patients with residual tumour, none of who died of disease during the 5 to 10 years of follow up. Two patients who died of recurrent carcinoma had no mucin production in the post-irradiated tumour tissues. The presence of mucin in irradiated carcinoma of cervix seems to infer a better prognosis and this may prove useful in the follow up of irradiated carcinomas. PMID- 1417085 TI - Pregnancy with an intrauterine device in situ and preterm delivery. AB - We determined the prevalence of preterm delivery in a population of women who conceived with an IUD in situ and compared the results with those in a group of women without any contraceptive method. The study group consisted of 16 women who conceived with a copper IUD in situ. The control group comprised 48 women matched for age, gravidity and parity. The prevalence of preterm delivery was significantly higher in the study group than in the control group (18.7% (3/16) vs 2% (1/48)), respectively. (P = 0.045, Fisher's exact test.) PMID- 1417086 TI - Condition at birth of infants with previously absent or reverse umbilical artery end-diastolic flow velocities. AB - In a case control study we assessed 47 fetuses with absent or reverse end diastolic flow velocities (AREDFV) of the umbilical artery with respect to the mode of delivery, fetal acidosis, and abnormal neurological evaluations at the time of discharge from the department of pediatrics. We also studied a control group which was matched for gestational age and had normal umbilical artery flow velocity waveforms. Fetuses with AREDFV were delivered almost exclusively by cesarean section which was usually done for fetal distress. The number of fetuses with abnormal neurological signs was significantly increased compared to the control group. Fetuses with AREDFV showed an increased incidence of fetal acidosis. Forty per cent of these fetuses were delivered within one day of the first abnormal flow measurement; Sixty per cent were observed clinically for up to four weeks before delivery. PMID- 1417087 TI - Reproductive performance after local and systemic prostaglandin for ectopic pregnancy. AB - The injection of different substances into early, unruptured tubal pregnancies is increasingly advocated. In this study, fertility was evaluated after treatment of tubal pregnancy by means of prostaglandins. The overall tubal patency rate was 86.4% and 14 of 20 patients (70%) could subsequently achieve pregnancy. PMID- 1417088 TI - Influence on erythropoietin levels of treatment with cisplatinum-endoxan. AB - Erythropoietin levels have been determined in 24 patients with different gynecologic malignancies, who were treated with cisplatinum and endoxan. A statistically highly significant decrease was demonstrated 2 h after starting treatment with a further significant decrease at 6 h. After 12 h the erythropoietin concentrations returned to values similar to those before treatment started. PMID- 1417089 TI - Culdocentesis is an obsolete diagnostic tool in suspected ectopic pregnancy. AB - We studied 332 patients with proven pregnancies. Prediction of hemoperitoneum by assessment of the Douglas pouch during bimanual examination had a false negative rate of 42.1%. The false negative rate for culdocentesis was 14.8%. It is therefore concluded that culdocentesis is not a useful tool in the diagnosis of suspected ectopic pregnancies. PMID- 1417090 TI - Congenital chylothorax in a trisomy 21 newborn. AB - We here report a case of trisomy 21 with congenital chylothorax. The patient was a male newborn who had been diagnosed as having trisomy 21 with congenital chylothorax. This is the fifth case of the both conditions in English literature. Congenital chylothorax is very rare in a trisomy 21 patient. There, however, may be causal relationship between the two conditions. PMID- 1417091 TI - [Substitution of inferior vena cava for Gore-Tex ring prosthesis: experimental study]. AB - We conducted an experiment in 10 mini-pigs, using the Goretex prosthesis to replace the inferior vena cava. Venous flow was increased by a distal arterio venous fistula to reduce the risk of thrombosis. The survival rate at 3 months was 60%. The foregoing results indicate that this replacement procedure should be considered in inferior vena caval replacement which, although rarely, might be warranted in the clinical course of renal adenocarcinoma. PMID- 1417092 TI - [Surgical adrenal gland pathology. Urologist's pathology]. AB - We reviewed 6 cases of unilateral adrenal tumor that had been treated during a 5 year period. The Turner-Warwick modified lateral approach was performed in all 6 cases. In our view, surgical treatment of unilateral adrenal tumors should be performed by the urologist. The high lumbar approach appears to be the most appropriate for unilateral adrenal tumor masses not larger than 6 cm. The surgical anatomy of the adrenal gland is briefly described. PMID- 1417093 TI - [Calcifications in renal adenocarcinoma. Image assessment in 17 cases]. AB - Of 60 renal adenocarcinoma tumors that had been diagnosed at our hospital between 1984 and 1990, 17 had presented intratumoral calcification. These 17 tumors with calcification were studied to assess the sensitivity of different techniques relative to detection, localization and morphologic characterization of the calcifications. We can conclude from the study that the use of CT and US not only raised detection rate (28%), but also permitted more precise evaluation of the calcified tumor mass. Furthermore, tumor spread beyond the calcified area was found to be a sign of malignancy. PMID- 1417094 TI - [Usefulness of catheter pyelography in ileal diversions and continent bladder replacement after radical cystectomy]. AB - Transcatheter ascending pyelography is commonly performed in the post-operative evaluation of patients submitted to ileal diversion or continent bladder replacement after radical cystectomy. The present study investigated the usefulness of this procedure in the control of these patients. Of 51 patients that underwent cutaneous ileal diversion, the IVP revealed a leak of the contrast medium in only one case (1.9%). Of the 18 patients that received a continent neobladder, radiologic signs of changes were detected in 6 cases (33.3%). The complications of the IVP in our patients were fever in 26 patients (37.7%) and septicemia in one patient (1.45%). Considering the information obtained and the rate of morbility, we believe that ascending pyelography through catheters is not justified in the routine post-operative control of patients who have undergone radical cystectomy and ileal diversion. However, it appears to be a useful procedure in those cases that have undergone bladder replacement and/or continent diversion procedures. PMID- 1417095 TI - [Behavior of the contralateral ureter following surgery for unilateral antireflux surgery]. AB - We present our experience of 44 cases with unilateral vesicorenal reflux that had been treated by ureteroneocystostomy using the Cohen technique. The reflux disappeared in 32 cases, it appeared in the contralateral ureter in 7 patients, it was ipsilateral in 2 and bilateral in 3. Of the 10 cases with contralateral reflux, 2 required surgery, while 8 were amenable to medical treatment. In our series, contralateral reflux appeared at random. Since the spontaneous cure rate was 80%, we believe that bilateral antireflux surgery for unilateral reflux is unwarranted. Urodynamic studies can be important in the indication for conservative treatment. PMID- 1417097 TI - [Integral urologic echography: retrograde sonourethrography]. AB - Herein we describe a new technique for urethral exploration which replaces conventional radiological urethrography to a large extent. Retrograde sonourethrography is capable of providing data different from those of radiology, eliminates most of the inconveniences of the radiologic techniques and provides images of the entire trajectory of the urethra. Because this procedure can be repeated as often as necessary, it is the diagnostic procedure of choice in urethral stricture, a persistent and recurrent pathological condition. The results of a study conducted in 30 patients with different urethral pathologies are presented. PMID- 1417096 TI - [High flow priapism]. AB - Four cases with high flow priapism are described herein. Patient evaluation included intracavernal blood-gasmetry, echo Doppler, selective arteriography of the pudendal artery. Three patients had a previous history of trauma and one patient was on psychotropics. The alpha-agonist drugs and the different shunt techniques did not achieve detumescence. Two embolization procedures of the internal pudendal artery were performed with good long-term results. The other two cases achieved spontaneous detumescence. No complications or secondary erectile dysfunction were observed. PMID- 1417099 TI - [Spontaneous extravasation of urine secondary to bladder carcinoma. Non-invasive therapy]. AB - A case of spontaneous urinary extravasation secondary to bladder carcinoma is described. The patient received systemic polychemotherapy which reduced tumor size and resolved renal ectasia and urinary extravasation. Spontaneous urinary extravasation secondary to bladder carcinoma is rare. For this reason we considered it of interest to report this case. PMID- 1417098 TI - [Endoscopic resection of tumor of the renal pelvis]. AB - We report on a patient who was submitted to percutaneous resection of a solitary, low grade urothelial transitional cell tumor of the renal pelvis. A review of the literature shoned endourologic treatment to be a valid in carefully selected cases. The measures to minimize the risk of tumor spread and the good results obtained are discussed. However, a longer follow up and larger series are necessary in order to draw definitive conclusions. PMID- 1417100 TI - [Fistula between ileal conduit and small intestine after cutaneous ureteroileostomy]. AB - We report on a case of ileal conduit-enteric fistula which appeared early after ureteroileostomy using the Bricker technique. The appearance of gastrointestinal content through the stoma was the only sign. An ileogram permitted making the diagnosis. Conservative treatment was instituted and the fistula resolved spontaneously. The different diagnostic and therapeutic aspects of this uncommon complication after ureteroileostomy are discussed. PMID- 1417101 TI - [Urachal leiomyoma]. AB - A case of leiomyoma of the urachus is reported herein. A review of the literature revealed only 6 cases have been reported. Its incidence is suspected to be higher, but this tumor type is only detected when it is large enough or when complications arise such as bleeding, infection, etc. There is no other data of interest except for its rarity. PMID- 1417102 TI - [Renal transplant and cutaneous ureteroileostomy. Report of 2 cases]. AB - Congenital or acquired pathology of the lower urinary tract currently does not preclude renal transplantation in patients with end-stage nephropathy. We report two cases of renal transplantation with ureteroileal cutaneous diversion in patients with a nonfunctional lower urinary tract due to bladder fibrosis secondary to urinary tuberculosis. We discuss the possibilities of the urodynamic study in the preoperative evaluation of patients with similar conditions. PMID- 1417103 TI - [Multiple organ metastasis following nephrectomy for renal carcinoma]. AB - We report a case of TNM stage II renal carcinoma with metastasis to lungs, contralateral adrenal gland and skin within 5 years following nephrectomy. The patient underwent lobectomy, adrenalectomy and cutaneous excision biopsy. The clinical course and management of metastases are discussed. PMID- 1417104 TI - [The sign of the prominent papilla]. PMID- 1417105 TI - Recovery from pulmonary hypertension in an adolescent with mixed connective tissue disease. AB - This paper describes the case of an 11 year old girl who presented with mixed connective tissue disease which was complicated by the development of pulmonary hypertension. This case is unique with respect to the young age of onset, the serial non-invasive method used to follow the disease process, and the favourable response to treatment with vasodilator and anti-inflammatory drugs. PMID- 1417106 TI - Palmar rheumatoid nodulosis associated with local pressure. AB - Rheumatoid nodulosis is a term used to describe adult patients with rheumatoid arthritis with little or no clinical joint inflammation who have numerous subcutaneous nodules indistinguishable from those of patients with active rheumatoid arthritis. This paper reports the case of a woman with quiescent rheumatoid arthritis who developed palmar nodulosis three weeks after the strenuous activity of painting her apartment. This case illustrates the direct association between the appearance of nodulosis and physical pressure despite inactive disease. PMID- 1417107 TI - Long term treatment of chronic Lyme arthritis with benzathine penicillin. AB - The cases are reported of two patients with chronic Lyme arthritis resistant to the recommended antibiotic regimens who were cured by long term treatment with benzathine penicillin. It is suggested that the sustained therapeutic levels of penicillin were effective either by the inhibition of germ replication or by lysis of the spirochaetes when they were leaving their sanctuaries. PMID- 1417108 TI - Ulcerative colitis complicating seronegative HLA-A2-B27 rheumatoid arthritis with sacroiliitis. AB - The case is reported of a 50 year old man with longstanding seronegative rheumatoid arthritis who developed ulcerative colitis. The patient also had sacroiliitis and his tissue was typed as HLA-A2-B27 several years before the bowel disease began. A possible overlap between primary inflammatory bowel disease, complications to the treatment of rheumatoid arthritis with drugs, and gastrointestinal rheumatoid vasculitis is discussed. PMID- 1417109 TI - From The Netherlands. PMID- 1417110 TI - Pseudohaemarthrosis: a new manifestation of Osler-Rendu-Weber disease. PMID- 1417111 TI - Lupus anticoagulant activity and anticardiolipin antibody titre in patients with systemic lupus erythematosus. PMID- 1417112 TI - Failure of cold pressor testing to induce changes in plasma renin activity or renal duplex sonography in patients with systemic sclerosis. PMID- 1417113 TI - Inactive alpha 1 antitrypsin in rheumatoid synovial fluid: oxidation, proteolysis, or complex formation? PMID- 1417114 TI - HLA-D region genes and rheumatoid arthritis. PMID- 1417115 TI - HLA-B27 subtypes: implications for the spondyloarthropathies. PMID- 1417116 TI - A 12 year follow up study in the general population on prognostic factors of cartilage loss in osteoarthritis of the knee. AB - The natural history and prognostic factors of cartilage loss in osteoarthritis of the knee were studied in subjects from a general population survey on rheumatic diseases in 1975-8. Baseline data were collected by questionnaire, physical examination, and weightbearing anteroposterior knee radiographs. Follow up of the subjects aged 46-68 years with radiological osteoarthritis grade 2-4 (Kellgren) took place in 1988-9. Cartilage loss was assessed by two observers who scored the change in joint space width between two radiographs. Thirty four per cent had cartilage loss. Prognostic factors and adjusted odds ratios (ORs) (95% confidence intervals) were: body mass index OR = 11.1 (3.3 to 37.3) fourth v first quartile; body weight OR = 7.9 (2.6 to 24.0) third v first tertile; age OR = 3.8 (1.1 to 13.4) > 60 v < or = 49 years; Heberden's nodes OR = 6.0 (1.5 to 23.1); clinical diagnosis of generalised osteoarthritis OR = 3.3 (1.3 to 8.3); and previous bow legs or knock knees OR = 5.1 (1.1 to 23.1). The relation of age with cartilage loss was also confounded by the presence of Heberden's nodes or a diagnosis of generalised osteoarthritis. There was no statistically significant relation for gender, meniscectomy, injury, uric acid concentration, chondrocalcinosis, smoking, and occupation related factors, except possibly standing. PMID- 1417117 TI - Scintigraphic assessment of osteoarthritis of the knee joint. AB - Clinical, radiographic, and scintigraphic abnormalities of the knee joint have been correlated in a cross sectional study of 100 patients with osteoarthritis. The group comprised 73 women and 27 men with a mean age of 65.7 years. One hundred and ninety one of the 200 knees had clinical (175) or radiographic (185) evidence of osteoarthritis, or both (161). Scintigraphic images of the knees were obtained 4-5 minutes (early phase) and 2.5-3.5 hours (late phase) after intravenous injection of 600 mBq of technetium-99m diphosphonate. Abnormal images were recorded in 162 knees (81%), and six different patterns were detected. Generalised isotope retention around the knee (early or late phase) was less common than focal areas of uptake around the joint margin (early or late phase) or in the patella or subchondral bone (late phase). Some knees with abnormal scans were normal on radiography (n = 7), or vice versa (n = 21). Different scan patterns correlated with different clinical and radiographic features: the generalised pattern correlated with pain (odds ratio (OR) = 45.1) and osteophytes (OR = 48.3); joint line retention correlated with subchondral bone sclerosis on radiography (OR = 62.1); and subchondral bone retention correlated with more severe radiographic changes. It is concluded that different patterns of scintigraphic abnormality reflect various aspects of the disease process of osteoarthritis. PMID- 1417118 TI - Effect of disease severity on rheumatoid arthritis concordance in same sexed siblings. AB - To assess the factors in a proband with rheumatoid arthritis (RA) that might predict the occurrence of the disease in siblings, 240 same sexed sibships (190 female, 50 male) in which the proband had classical or definite RA were clinically and immunologically documented. Sibship concordance rates were consistently higher for features of severe disease in the proband, reaching statistical significance for a clinical score of disease severity (the SS index). This trend for increasing disease severity to be associated with increasing sibship concordance rates could not be accounted for by age or disease duration of the proband. These results suggest that siblings of probands with severe RA are at greater risk of developing RA than those of probands with mild disease. PMID- 1417119 TI - Ankylosing spondylitis and monoclonal gammopathies. AB - From 1960 to 1990, 557 patients with ankylosing spondylitis (428 men, 129 women) were diagnosed and indexed in the department of rheumatology. Monoclonal gammopathies were found in seven (five men, two women) patients (1.3%). With one exception, ankylosing spondylitis preceded monoclonal gammopathies by many years. The distribution of the isotypes of the mIg found in these seven patients was striking when compared either with previous reports of an association between ankylosing spondylitis and monoclonal gammopathies or with local data on the epidemiology of monoclonal gammopathies: five patients with IgG, four of them of the lambda (lambda) type, and two IgM, both of the kappa (kappa) type were found; no patients with mIgA were recorded. Two patients were HLA-B27 positive and had slight and transient monoclonal gammopathies, whereas three subjects were HLA-B27 negative and had important spikes, corresponding in two subjects to malignant diseases. This observation raises the question of whether the coexistence of HLA B27 and ankylosing spondylitis might provide a protective action. Epidemiological studies are required to clarify such points. PMID- 1417120 TI - Cellular immunity to cartilage proteoglycans: relevance to the pathogenesis of ankylosing spondylitis. AB - Cellular immunity to cartilage proteoglycans may be responsible for sustaining chronic inflammation in ankylosing spondylitis. This hypothesis was examined by measuring peripheral blood and synovial fluid mononuclear cell proliferation in five preparations of human cartilage proteoglycan monomer in vitro. Peripheral blood mononuclear cells from 25 patients and synovial fluid mononuclear cells from five patients were compared with those from normal and disease control subjects matched for age. No significant differences were found between the three groups. This suggests that autoimmune responses to cartilage proteoglycans are unlikely to play a significant part in the pathogenesis of ankylosing spondylitis. PMID- 1417121 TI - Plasminogen activators in synovial fluid and plasma from patients with arthritis. AB - The activity of plasminogen activators and inhibitors in the synovial fluid and plasma of patients with various forms of chronic arthritis was characterised. Tissue-type plasminogen activator antigen (t-PA:Ag), urokinase-type plasminogen activator antigen (u-PA:Ag), the proenzyme single chain u-PA (scu-PA), and plasminogen activator inhibitor (PAI) were measured in the synovial fluid and plasma of 22 patients with seropositive rheumatoid arthritis (RA), 13 with seronegative RA, and 23 patients with various forms of arthritis. In all patient groups the levels of t-PA:Ag in synovial fluid were lower and the levels of u PA:Ag and PAI higher than plasma levels. Synovial fluid u-PA was more activated than plasma u-PA. Comparison of the patient groups showed that the largest differences between fibrinolytic parameters in synovial fluid and plasma were present in patients with seropositive RA followed by patients with seronegative RA and patients with various forms of arthritis. This order paralleled the functional and radiological scores of joint destruction in the patient groups studied. The results of this study indicate that suppression of t-PA production and enhancement of u-PA synthesis and activation in arthritic joints are associated with the clinical severity of arthritis. PMID- 1417122 TI - Action of sodium aurothiomalate on erythrocyte membrane. AB - The number of sulphydryl groups on the erythrocyte membrane has been assessed as a function of nutritional status for two groups of patients, one receiving non steroidal anti-inflammatory drugs (NSAIDs) and the other receiving sodium aurothiomalate (Myocrisin). The patients receiving NSAIDs had a significantly higher number of sulphydryl groups in both the glucose depleted and glucose activated states than the patients receiving sodium aurothiomalate. The study focuses on the hexose transport protein where there is a specific binding site for gold using the two sulphydryl residues on helices 11 and 12 of the protein. The data suggest that the strong binding of gold to the erythrocyte membrane occurs via thiol pairs rather than by isolated sulphydryl groups and that there are possibly two further binding sites for gold on the membrane, the identities of which are still unclear. PMID- 1417123 TI - Night pain in arthritis: patients at risk from prescribed night sedation. AB - To assess the problem of night pain and the use of hypnotic drugs in patients with rheumatic diseases 165 consecutive patients (mean age 58.5 years) were assessed and questioned about night pain and the use of drugs including night sedation. Most of the patients (106 (64%)) were women. A total of 32 (19%) patients were receiving night sedation for a mean duration of 43.9 months. Fourteen patients (13 women) were using these drugs to treat insomnia related to pain. The mean visual analogue pain score for night pain showed a significant difference between those receiving night sedation (5.2) and those who were not (3.7). Of the 70 patients who answered the Stanford Health Assessment Questionnaire (HAQ), those receiving night sedation also had a significantly higher mean score (1.91) than those who were not (1.2), suggesting that patients receiving night sedation were more clinically disabled. Codeine was used by more (34%) patients receiving night sedation than those who were not (18%) suggesting that those receiving night sedation had more pain. These results highlight the need for better pain management in patients with rheumatic diseases to minimise the risk of prescribing addictive drugs such as hypnotic drugs and codeine. PMID- 1417124 TI - Repetitive strain disorder: towards diagnostic criteria. AB - Thirteen women (mean age 48.2 years; range 25-60 years) all of whom had developed musculoskeletal symptoms during employment in an industrial job with repetitive tasks were referred by their trade unions for adjudication on the cause of symptoms. One had rheumatoid arthritis. A study of the other 12 women provided an opportunity to document the natural history of repetitive strain disorder. Early symptoms of weakness were diffuse but were always relieved by rest. Several months later localisation of symptoms at a tendon, nerve, or enthesis could be predicted from the analysis of the action required in the particular repetitive task. Six of the 12 women required an operation several years later, thus providing histological confirmation of the presence of a lesion. Early loss of grip strength measured by a sphygmomanometer cuff compared with an unaffected control subject and improved by rest may be the most valuable sign in excluding compensation neurosis. The estimated prevalence of repetitive strain disorder defined by these strict criteria was at least 2% in conveyor belt workers. PMID- 1417125 TI - Detection of cytokine activated chondrocytes in arthritic joints from pigs infected with Erysipelothrix rhusiopathiae. AB - Chronic polyarthritis was induced in pigs by injection of Erysipelothrix rhusiopathiae and the in vivo activation of chondrocytes by cytokines was then investigated in the affected joints by immunocytochemistry. A polyclonal antiserum which recognises surface markers on in vitro interleukin 1 activated porcine chondrocytes was used to detect activated chondrocytes in all zones of the cartilage from diseased joints. In contrast, cartilage removed from an unaffected joint in the same animal showed no chondrocyte activation. Inflammatory synovial tissue removed from diseased joints and cocultured with cartilage from the unaffected joint induced activation of adjacent chondrocytes. The presence of interleukin 1 in the inflammatory cells of the synovium was confirmed and major histocompatibility complex (MHC) class II antigens were detected as a marker of synovial activation. Chondrocytes were found not to express class II antigens in cartilage from either the diseased or the unaffected joint. These observations show that the porcine erysipelas model of arthritis will be useful in facilitating a novel approach to monitoring the behaviour of individual chondrocytes under pathophysiological conditions. PMID- 1417126 TI - Dependence of proteoglycan induced arthritis in BALB/c mice on the development of autoantibodies to high density proteoglycans. AB - BALB/c mice were immunised with high or low density native human cartilage proteoglycans, or the respective core proteins obtained from chondroitin ABC lyase digestion. Mice injected with high density native proteoglycans developed arthritis whereas mice injected with low density proteoglycans or with core proteins did not. Analysis of the immune response by enzyme linked immunosorbent assay (ELISA) and western blot showed a stronger and more polyspecific response in animals injected with low density proteoglycans compared with mice with arthritis which had been injected with high density proteoglycans. Autoantibodies to mouse high density proteoglycans were only present in mice injected with native human high density proteoglycans, however. The data suggest that an arthritogenic epitope lies within the glycosaminoglycan rich region of the native proteoglycan molecule, which may induce an autoantibody response and subsequently arthritis in BALB/c mice. PMID- 1417127 TI - Uridine diphosphoglucose dehydrogenase activity in synovial lining cells in the experimental antigen induced model of rheumatoid arthritis: an indication of synovial lining cell function. AB - Uridine diphosphoglucose dehydrogenase (UDPGD) is the enzyme responsible for the production of uridine diphospho(UDP)-glucuronate, an essential monosaccharide in the biosynthesis of hyaluronan, which is found in high concentrations in normal synovial fluid. Synovial lining cells have been implicated in the synthesis of hyaluronan, but the degree to which they are adapted metabolically to this function in normal and inflamed synovium has not been established. Using a quantitative cytochemical method it was shown that synovial lining cells from chronically inflamed rabbit synovium had significantly lower UDPGD activity per cell than the lining cells of normal synovium. These findings suggest that the lining cells of normal non-inflamed synovium may be enzymatically adapted for the synthesis of hyaluronan and that this may be an indication of a specific role of synovial lining cells in the maintenance of normal joint function. PMID- 1417128 TI - Complications associated with labial salivary gland biopsy in the investigation of connective tissue disorders. PMID- 1417129 TI - Remission of scleroderma during chemotherapy for lymphoma. AB - Temporary remission of scleroderma during the successful treatment of an associated malignant lymphoma by chemotherapy is reported in a patient with systemic sclerosis and mixed connective tissue disease. There is a well established relation between malignant disease and polymyositis/dermatomyositis but no overall association with systemic sclerosis or mixed connective tissue disease. Reports of the coexistence of malignancy and systemic sclerosis, however, emphasise a close temporal relation in their occurrence. A review of published work has identified several postulated mechanisms for this relation which may explain the response to chemotherapy. PMID- 1417130 TI - Bone mineral density and osteoarthritis. PMID- 1417131 TI - Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study. AB - Serum rheumatoid factors (RF) were measured yearly in 135 women with rheumatoid arthritis by the Waaler-Rose and latex fixation tests and IgM, IgA, and IgG RF were measured by enzyme linked immunosorbent assays (ELISAs). The patients were followed up from an early phase of the disease for a mean duration of six years. Patients with a persistently positive RF test, irrespective of the type of test used, had more radiological abnormalities, more disease activity, worse functional ability, more extra-articular manifestations, and needed more treatment with second line drugs than patients with persistently negative or variably positive and negative test results during the follow up. Increased RF levels, especially a high level of IgA RF within three years of the onset of symptoms, was prognostic for a more severe disease outcome six years after the onset of symptoms. PMID- 1417132 TI - Decreased level of antibodies against Helicobacter pylori in patients with rheumatoid arthritis receiving intramuscular gold. AB - BACKGROUND: Sodium aurothiomalate has been reported to have in vitro activity against Helicobacter pylori. Intramuscular gold, as given to patients with rheumatoid arthritis (RA), may therefore influence the colonisation of the gastric mucosa with H pylori. METHODS: Two groups were compared. One group of 42 patients was treated with intramuscular gold; the other group of 58 patients was treated with antimalarial drugs. Antibodies to H pylori (IgA and IgG) were assessed by an enzyme linked immunosorbent assay (ELISA) and total IgA and IgG were measured by nephelometry. RESULTS: IgA and IgG antibody titres against H pylori and total IgA and IgG levels were lower in the patients treated with gold than in the group treated with antimalarial drugs. The ratio of IgA antibodies to H pylori to total IgA antibodies and the ratio of IgG antibodies to H pylori to total IgG antibodies were lower in the group treated with gold. The percentage of seropositivity to H pylori was significantly lower in the group treated with gold than in the group treated with antimalarial drugs for the two IgA antibodies (35 and 55% respectively) and IgG antibodies to H pylori (40 and 65% respectively). CONCLUSIONS: Although this study cannot completely exclude the possibility that a suppressive effect of intramuscular gold on total immunoglobulin production plays a part in the decrease in the titres of IgA antibodies to H pylori and IgG antibodies to H pylori, the lower ratios of antibodies to H pylori to total immunoglobulin antibodies and the lower percentages of seropositivity to H pylori in the group treated with gold suggests that treatment with intramuscular gold decreases H pylori colonisation. PMID- 1417133 TI - Recombinant human interferon gamma in the treatment of rheumatoid arthritis: double blind placebo controlled study. AB - Interferon gamma (IFN gamma) has been advocated in open studies as a beneficial remission inducing drug for the treatment of rheumatoid arthritis (RA). The work reported here was designed to assess the therapeutic potential of IFN gamma in the treatment of RA in a double blind placebo controlled study. It was found that patients treated with IFN gamma improved significantly with respect to morning stiffness, grip strength, swelling of an index joint, and erythrocyte sedimentation rate. Furthermore significantly more responders (according to predetermined response criteria) were found in the group treated with IFN gamma. Only minor adverse effects and no significant toxicity with respect to clinical or laboratory parameters were observed. PMID- 1417134 TI - Glutathione redox cycle enzymes and selenium in severe rheumatoid arthritis: lack of antioxidative response to selenium supplementation in polymorphonuclear leucocytes. AB - The antioxidant capacity of the glutathione redox cycle and the concentrations of selenium in serum, red blood cells or whole blood, and polymorphonuclear leucocytes was evaluated in nine patients with severe rheumatoid arthritis (RA) and eight healthy controls receiving daily supplementation with 250 micrograms selenomethionine for six months. Serum and whole blood concentrations of selenium and the activity of the selenium dependent enzyme glutathione peroxidase (GSH-Px) were low in the serum, red blood cells, and polymorphonuclear leucocytes of patients with RA before selenium supplementation. During supplementation serum and whole blood concentrations of selenium and the activity of GSH-Px in serum and red blood cells of patients with RA and serum GSH-Px in controls increased. Selenium and GSH-Px in polymorphonuclear leucocytes were unaffected in patients with RA in contrast with the controls where both were augmented. Glutathione reductase activity in the red blood cells and polymorphonuclear leucocytes of patients with RA was low but increased during selenium supplementation. Whole blood concentrations of glutathione were slightly lower in patients with RA than controls and no difference in the content in polymorphonuclear leucocytes was found between the groups. The activity in red blood cells of glucose-6-phosphate dehydrogenase was high in patients with RA, indicating sufficient function of the hexose monophosphate pathway. The reduced antioxidant activity of the glutathione redox cycle in patients with severe RA was mainly due to the low availability of selenium. This was further supported by the response to selenium supplementation in serum and red blood cells. In the polymorphonuclear leucocytes, however, no biochemical effects of selenium supplementation were seen. This lack of antioxidative response could play a pathogenetic part in inflammation in patients with RA. PMID- 1417136 TI - Correlation of antibodies to ribosomal P protein with psychosis in patients with systemic lupus erythematosus. AB - Ninety one Japanese patients with systemic lupus erythematosus (SLE) were studied to determine the clinical significance of antibodies to ribosomal P protein (anti P). Anti-P was detected by western blotting in 38 of 91 patients (42%). Clinical symptoms of SLE were compared between patients with and without anti-P. The occurrence of lupus psychosis was significantly higher in patients with anti-P than in those without anti-P (9/38 v 1/53). No significant association was found between anti-P and other symptoms of SLE. These data strongly support the suggestion proposed by previous workers that anti-P is a marker autoantibody for the development of lupus psychosis. PMID- 1417135 TI - Systemic lupus erythematosus in men: clinical and immunological characteristics. AB - Although systemic lupus erythematosus (SLE) has traditionally been considered a disease of women, men may also be affected. Thirty of 261 patients (12%) with SLE seen in this hospital were men. Arthritis was less common as a first symptom in the men, although this group of patients had discoid lesions and serositis more often than the women. During the follow up a lower incidence of arthritis and malar rash and a higher incidence of other skin complications including discoid lesions and subcutaneous lupus erythematosus was found in the men. The incidence of nephropathy, neurological disease, thrombocytopenia, vasculitis, and serositis, was similar in the two groups. No significant immunological differences were found between men and women. These features indicate that several gender associated clinical differences may be present in patients with SLE. PMID- 1417138 TI - Fracture thresholds in osteoporosis: implications for hormone replacement treatment. AB - The bone mineral densities of the lumbar spine and femoral neck were determined by dual energy chi ray absorptiometry in 110 women aged 40-82 years (average 65 years) with spinal osteoporosis who had had at least one atraumatic vertebral compression fracture and in 1026 normal women aged 40-79 years (average 52 years). The women with osteoporosis showed a significant decrease in bone mineral density (BMD) at the lumbar spine and femoral neck compared with age matched normal women (sixth decade of life -26% spine, -23% femoral neck; seventh decade 26% spine, -16% femoral neck). The fracture threshold, defined as the 90th centile of spinal BMD for women with osteoporosis, was 0.81 g/cm2 at the lumbar spine and 0.656 g/cm2 at the femoral neck. Five per cent of normal women aged 40 49 years, 20% aged 50-59 years, and 45% aged 60-69 years had a BMD below this threshold. To maintain the bones of women above the fracture threshold until the age of 70 years about 50% of postmenopausal women need hormone replacement therapy. However, if the BMD is to be kept above the fracture threshold for a women's lifetime, e.g. until the age of 80-90 years, then most women will need treatment, though for various lengths of time depending on their initial BMD. Measurements of BMD in postmenopausal women currently help in identifying the risk of osteoporotic fractures but in the lifetime assessment of risk in a single subject they may have a more important role in deciding the duration of hormone replacement therapy. PMID- 1417137 TI - Preliminary observations of chondral abrasion in a canine model. AB - Articular cartilage repair was followed for one year in skeletally mature dogs after destabilisation by anterior cruciate ligament transection of the stifle joint (CT), abrasion of the inferior medial condyle (ABR) to bleeding bone, or anterior cruciate transection followed by chondral abrasion (CT/ABR). ABR animals formed repair cartilage at the abrasion site (ABR and CT/ABR) at six months as determined by arthroscopy and at necropsy. CT and CT/ABR animals had an additional cartilage ulcer on the superior aspect of the medial condyle. The abraded site extended in CT/ABR condyles. Repair cartilage (ABR and CT/ABR) contained reduced amounts of proteoglycan as seen by histological loss of safranin O staining and reduced uronic acid content. Fibrocartilage was suggested by histological appearance, hypocellularity, and a higher hydroxyproline content. In contrast with ABR animals, the repair cartilage in the CT/ABR animals contained near normal amounts of hydroxyproline. Collagen profiles of abrasion site repair cartilage in ABR animals had more types I and V collagens, similar amounts of type VI collagen, and decreased amounts of types II, IX, and XI collagens than CT/ABR animals. The results of this study are consistent with abrasion chondroplasty leading to a repair cartilage. Despite extended ulcers, repair cartilage from the destabilised joint (CT/ABR) animals was more hyaline like in its hydroxyproline content and collagen composition than repair cartilage from the stable joint (ABR animals). In these models additional measures appear to be needed as the defects induced by abrasion chondroplasty did not form a functional hyaline cartilage. PMID- 1417139 TI - Differential involvement of the dorsal and lumbar spine in osteoporosis. AB - The presence of normal bone density values in the lumbar spine is often assumed to exclude osteoporosis. Eleven cases are reported in which normal lumbar spine bone density and radiology were associated with one or more dorsal spine fractures; the diagnosis was postmenopausal osteoporosis in eight patients and corticosteroid induced osteoporosis in three. These findings suggest that spinal osteoporosis may sometimes be a focal disorder and emphasise the need for dorsal spine radiology in addition to bone densitometry in patients with strong risk factors for osteoporosis or with clinical evidence of the dorsal spine being affected. PMID- 1417140 TI - False positive results for antibody to HIV in two men with systemic lupus erythematosus. AB - False positive results were obtained for HIV tests in two men with active systemic lupus erythematosus (SLE) who were suspected of being infected with HIV because of fever, weight loss, lymphadenopathy, and inflammatory myopathy. Enzyme linked immunosorbent assays (ELISAs) for HIV were twice positive when tested three times over a period of six months. Western blot analysis showed reactivity against the gp41 band in patient 1. False positive results for HIV tests can occur in patients with SLE, potentially leading to an erroneous diagnosis of HIV infection. PMID- 1417141 TI - Primary idiopathic osteolysis: description of a family. AB - A clinical, analytical, and radiological study was carried out on three members of the same family with multicentric idiopathic osteolysis. Transmission appeared to be via the dominant autosome present in the mother and two daughters. In the daughters osteolysis was seen in the carpal and tarsal bones, whereas in the mother radiology showed it to be in the phalanges of the hands and feet. PMID- 1417142 TI - Mycotic aneurysm of the aortic arch masquerading as systemic lupus erythematosus. AB - The case is described of a patient with mycotic aneurysm of the aortic arch whose clinical and serological features were indistinguishable from those of systemic lupus erythematosus. Surgical resection and repair of the aneurysm resolved her clinical symptoms and the serological abnormalities. PMID- 1417143 TI - Temporal arteritis: a form of systemic panarteritis. AB - The case is reported of a patient with giant cell arteritis affecting several organs. The triggering cause of death was a brainstem infarction due to basilar artery thrombosis. The necropsy showed the systemic character of the disease affecting the coronary, bronchial, and ovarian arteries. PMID- 1417144 TI - Systemic lupus erythematosus induced by isoniazid. AB - The case is described of a 73 year old man who presented with a lupus-like syndrome related to treatment with isoniazid and had IgG antinuclear antibodies against the nucleo-histone complex (H2A-H2B)-DNA. After a short course of treatment with prednisone and discontinuation of isoniazid the patient's lupus symptoms resolved and a gradual decrease in antibodies to (H2A-H2B)-DNA occurred. This case suggests that isoniazid is capable of inducing an autoantibody specificity associated with drug related lupus. PMID- 1417145 TI - Misoprostol in the prevention of gastroduodenal damage in rheumatology. AB - Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) are at an increased risk of gastroduodenal erosions, ulcers, and the associated complications of haemorrhage, perforation, and death. Many NSAID associated ulcers that bleed or perforate have been asymptomatic until the time of presentation and conversely many patients with dyspepsia do not have ulcers. Symptoms are a poor guide to the presence of an ulcer. During continued treatment with NSAIDs misoprostol is the best choice for NSAID induced gastroduodenal damage; it achieves higher rates of healing than other drugs in these circumstances. Misoprostol is superior to other drugs in the prevention of gastric damage but misoprostol and H2 antagonists are of similar benefit in the duodenum. Prophylactic studies have all used endoscopic damage as an endpoint, and much larger studies will be needed to show an effect of misoprostol on the incidence of ulcer complications. There are no clear guidelines as to which patients should receive prophylactic treatment with misoprostol but those particularly at risk of ulcer complications--that is, those with previous peptic ulceration, the elderly, medically unfit, patients receiving large doses of NSAIDs, and those patients receiving steroids in addition to NSAIDs--should be considered. PMID- 1417147 TI - Class II antigen induction in cartilage. PMID- 1417146 TI - Sex ratios, HLA markers, and rheumatic diseases. PMID- 1417148 TI - Reduced serum beta 2-glycoprotein I in SLE. PMID- 1417149 TI - Anticardiolipin antibodies in rheumatoid arthritis. PMID- 1417150 TI - Multiple leiomyomas of the skin in RA. PMID- 1417151 TI - Pachydermodactyly: confused with JCA. PMID- 1417152 TI - Mycobacterium Kansasii osteitis of the ischium. PMID- 1417153 TI - Age at presentation with ankylosing spondylitis. PMID- 1417154 TI - Pregnancy and antiphospholipid antibodies. PMID- 1417155 TI - Antireticulin antibodies in systemic sclerosis. PMID- 1417156 TI - Antiribosomal P antibodies and lupus psychosis. PMID- 1417157 TI - [Evaluation of the efficacy of fenitrothion (Sumithion PM40) on vector density and the prevalence of malaria in Pout (Thies, Senegal)]. AB - House-spraying with fenitrothion for malaria control was evaluated in three villages of the Pout rural community (Senegal) between August 1988 and October 1990. The baseline data were collected during the first year. The malaria vector was identified as Anopheles arabiensis and the highest malaria prevalence was observed in October 1988 (38%) in the child population (2-9 years old). A simple round of fenitrothion house-spraying at 1 g/m2 was carried out in the second part of July 1989. About 90% of the houses were treated. The malaria vector was reduced to negligible density and a rapid decrease of malaria prevalence was observed. In this area of short seasonal transmission, where the stability of malaria is low, one single round of spraying led to a marked reduction of malaria transmission and prevalence. The cost of the treatment was about 50 US cents per capita. PMID- 1417158 TI - [Serological evidence of the existence of a wild reservoir of Trypanosoma brucei gambiense in the Pendjari biosphere reservation in the Republic of Benin]. AB - In the national park of Pendjari, situated in the North-West of Benin, 91 wild animals, belonging to seven species, were darted. Thick and thin blood smears were examined for trypanosomes and plasma for trypanolytic antibodies against 6 antigenic variants of Trypanosoma brucei gambiense. Parasites were found in 13.92% and trypanolytic antibodies in 20.88% of the samples. A total of 28.57% of animals were positive by at least one of the two test systems used. Morphologically Trypanosoma congolense, T. vivax and T. brucei were identified. Overall prevalence was 40% in Adenota kob (n: 50), 13.63% in Alcelaphus buselaphus (n: 22), 10% in Hippotragus equinus (n: 10), 33% in Kobus defassa (n: 3), 0% in Phacochoerus aethiopicus (n: 3) and in Syncerus caffer (n: 2). The only lion (Panthera leo) examined was serologically positive. The results indicate that the wild animals are reservoirs of animal trypanosomes and suggest that among them Adenota kob and Panthera leo are carriers of T. brucei gambiense, one of the etiological aspects of human trypanosomiasis. PMID- 1417159 TI - [Ivermectin or diethylcarbamazine in spaced dosages in Bancroft's filariasis: which protocol?]. AB - 58 apparently healthy Polynesian Wuchereria bancrofti carriers were randomly allocated to 5 treatment groups: 1) two annual doses of ivermectin 100 mcg/kg, 2) three semi-annual doses of ivermectin 100 mcg/kg, 3) two annual doses of diethylcarbamazine (DEC) 3 mg/kg, 4) semi-annual doses of DEC 3 mg/kg, 5) two annual doses of DEC 6 mg/kg. Results observed during the 12-month period which followed last treatment have confirmed that efficacy of ivermectin is higher than that of DEC in terms of immediate clearance or complete negativation of microfilaremia, but not in terms of sustained reduction and that efficacy of repeated single doses of either DEC 3 mg/kg or ivermectin 100 mcg/kg is much higher when given semi-annually than annually. They also have indicated that (i) 6 months after last treatment: 3 semi-annual doses of 100 mcg/kg of ivermectin have resulted in high reduction of microfilaremia (85%) and, 2 annual doses of 6 mg/kg and 3 semi-annual doses of 3 mg/kg of DEC have resulted in even greater reduction (96 and 98% respectively) and (ii): 12 months after last treatment, the greatest reductions of microfilaremia (95 and 92%) have been observed in carriers treated, respectively, with 3 semi-annual doses of 3 mg/kg or with 2 annual doses of 6 mg/kg of DEC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417160 TI - HIV screening and confirmation: a simplified and less expensive testing algorithm. AB - In this study we investigated the performance of fourteen different assays capable of simultaneously detecting antibodies to HIV-1 and HIV-2, referred to as combined screening assays (CSAs), on a panel of 371 sera, with a prevalence of 51.5% and 1.3% for HIV-1 and HIV-2 antibodies respectively. The geographic distribution of the sera was as follows; Europe (121), Africa (203) and Latin America (47). These sera were collected from different clinical groups of patients; Asymptomatic (36), AIDS-Related Complex/AIDS patients (18), infected individuals with generalised lymphadenopathy (12), blood donors (149), and subjects with unknown clinical status (156). The Dupont Western blot (WB) kit for detection of HTLV-III antibodies and the Pasteur new Lav-Blot II kit were used for the confirmation of HIV-1 and HIV-2 infection respectively. Of the 14 tests studied, 9 were enzyme linked immunosorbent assays (ELISAs), and 5 were non-Elisa tests requiring visual reading. An alternative approach for HIV antibody testing was studied restrospectively, whereby sera positive in an initial CSA (A) were retested on a second CSA (B), that was different from the first. The use of WB was limited to sera that gave discrepant (A+B-) results in the two CSAs. A positive result in both CSAs was reported as anti-HIV positive. A negative result in the first CSA was reported anti-HIV negative. Sensitivity, specificity, cost, and the delta (delta) values (delta values of the ELISA assays) were taken into consideration when selecting suitable pairs of assays. All the ELISAs scored 100% sensitivity, but for the non-ELISAs, the sensitivity ranged from 96.0% to 100%. The specificity for the ELISAs and non-ELISAs varied from 87.4% to 100% and from 51.4% to 100% respectively. Delta (delta) values for the ELISAs ranged from 3.82 to 136.68 and from -1.15 to -3.08 for the anti-HIV positive and anti-HIV negative populations respectively. Of the 121 test combinations studied, 9 (7.4%) pairs yielded 100% sensitivity and specificity and 61 (50.4%) pairs of CSAs required further testing on WB. This implies 100% positive predictive value, at a cost that was on average 6 times less, and a testing time that was 5 times faster than the conventional algorithm. We conclude that there are several combinations of pairs of CSAs that can be used in the alternative algorithm that can provide accurate results at a much lower cost than the conventional algorithm requiring confirmation by WB of all initially reactive CSA results.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1417161 TI - [Community health workers are capable of determining reliably the target population for health programs]. AB - The target population is a key concept for the planning and evaluation of health services. However, in developing countries, health professionals in the field are often uneasy with the determination of the population denominator. In Zaire, where reliable demographic data are hardly available, we make use of two different methods aimed to the determination of the size of the target population: (1) an exhaustive population based survey performed by trained interviewers, and (2) a rapid census of the target population performed by community health workers. This paper presents both the results of a demographic survey organized in 1984, and two consecutive census performed by community health workers in 1986 an 1988, in the same area (Northern-Kivu, Zaire). Our results suggest that community health workers under close supervision are able to perform rapidly and at low cost a reliable collection of the demographic data needed for the implementation and monitoring of health programmes at the local level. PMID- 1417162 TI - [The severity of a snake bite. Apropos of 3 case reports in the Congo]. AB - Three observations of sanke-bite that occurred in the Congo are reported: the bite of an aglyph colubridae (Philothamnus nitidus loveridgee) that was severe; the bite of an Atheris s.p. with moderate symptoms; the bite of a Naja melanoleuca remained totally asymptomatic. PMID- 1417164 TI - [Primary health care: birth spacing and priorities]. PMID- 1417163 TI - Kashin-Beck disease. AB - The article describes the history, clinical picture and anatomopathological changes of Kashin-Beck disease with reference to the stages of the disease which are at present agreed upon. Specific reference is made to the occurrence of the disease in Tibet. An overview is given of the different proposed etiologies. PMID- 1417165 TI - Only the serum-resistant bloodstream forms of Trypanosoma brucei rhodesiense express the serum resistance associated (SRA) protein. AB - The Trypanosoma brucei species consists of three subspecies. T. b. rhodesiense and T. b. gambiense are human infective forms, while T. b. brucei is lysed upon exposure to the cytotoxic factor in normal human serum. T. b. rhodesiense can however occur as a serum-resistant (R) and as a serum-sensitive form (S). In a study of the molecular basis of serum resistance in T. b. rhodesiense it was shown that in the cloned ETaR1-repertoire only the serum-resistant variants express specific transcripts, encoding a protein with VSG-characteristics. When a serial of freshly isolated T. b. rhodesiense isolates was tested, the presence of the R-transcripts in the serum-resistant populations was confirmed. The absence of the serum resistance associated (SRA) mRNAs in several isolates from T. b. brucei and especially T. b. gambiense (including an a-typical one), indicates that more than one mechanism might be involved in the phenomenon of serum resistance in the T. brucei group. Neither T. evansi, nor T. equiperdum expresses the SRA-transcripts. Interestingly, the transcription of the R-specific transcripts is not maintained during the life cycle of T. b. rhodesiense; in the procyclic forms the SRA-mRNAs are no longer present. PMID- 1417166 TI - Molecular aspects of Trypanosoma cruzi interaction with host cell and parasite differentiation mechanisms. PMID- 1417167 TI - Mechanisms underlying trypanosome-elicited immunosuppression. AB - T-cell proliferative responses of lymph node cells are profoundly suppressed during experimental infections of mice with Trypanosoma brucei. The active suppression of lymph node T-cell proliferative responses is attributed to the coexistence of at least two unlinked suppressive mechanisms that block different T-cell regulatory steps and operate through different effector mechanisms. The generation of prostaglandin-producing macrophages is entirely responsible for the suppression of IL-2 production whereas the induction of a prostaglandin independent suppressive mechanism accounts for the suppression of the expression of IL-2 receptors (IL-2R). Both mechanisms are mediated by the cells that co purify which macrophages. Despite an impairment at the level of T-cell proliferation, lymph node cells from T. brucei infected animals produce substantial amounts of interferon-gamma (IFN-gamma) and this lymphokine participates in the down-regulation of IL-2R expression. T-brucei-pulsed macrophage cell lines acquire concomitantly the potential to suppress T-cell proliferative responses and to stimulate CD8+ T-cells to secrete IFN-gamma. The sensibilization of CD8+ T cells by T. brucei-pulsed macrophages might be mediated by TNF-alpha. Collectively, these results indicate that the uptake of T. brucei by macrophages, either in vivo or in vitro, results in the generation of suppressive cells that annihilate T-cell proliferative responses. Furthermore, at least two cytokines (i.e., TNF-alpha and IFN-gamma) are released during these interactions. Besides playing a role in the pathway of T-cell immunosuppression, TNF-alpha and IFN-gamma could also contribute to immunopathological features that occur during trypanosome infections. PMID- 1417168 TI - Advances in sleeping sickness therapy. AB - The efficacy and adverse effects of nifurtimox and DFMO in the treatment of sleeping sickness are reviewed. Both new substances constitute effective novel therapeutic agents for gambiense sleeping sickness, including melarsoprol refractory disease. DFMO is not very active in rhodesiense sleeping sickness and experience with nifurtimox in this form of trypanosomiasis is too limited to draw valid conclusions. The toxicity of nifurtimox and DFMO is not negligible. Optimum dosage and duration of therapy, modes of administration and potential for large scale use are discussed. Some recent results obtained with the classical trypanocide melarsoprol are presented to facilitate comparison. The current availability of several effective late-stage drugs (melarsoprol, nifurtimox and DFMO), that show synergistic activity in experimental models, should allow the establishment of optimum combination treatment regimens. PMID- 1417169 TI - Diagnosis of human African trypanosomiasis. PMID- 1417170 TI - Eradication of Triatoma infestans: a new regional programme for southern Latin America. PMID- 1417171 TI - [Geometry and passion. The campaign against sleeping sickness]. PMID- 1417172 TI - To Ollie, Ray and Isidore, Mort and Sally. An homage to teachers. PMID- 1417173 TI - Effect of intraportal glucose infusion on hepatic glycogen content and degradation, and outcome of liver transplantation. AB - Recent animal studies suggest that nutritional repletion may improve function of liver allografts, and the authors have found that intraportal glucose infusion in pigs produces rapid and substantial hepatic glycogenation. A controlled prospective randomized study in 32 patients was done to determine glycogen content and degradation in human livers during transplantation, and the effect of intraportal glucose-insulin infusions during the donor operation on these variables and on outcome of transplantation. Peripheral blood glucose concentrations were "clamped" at 14 mmol/L during the glucose-insulin infusion. Liver biopsies were taken at various stages of the procedure. Liver glycogen decreased 2.0 +/- 1.2 g/100 g dry weight liver (mean +/- standard error of the mean) in controls, but increased 6.8 +/- 1.8 g/100 g dry weight in glucose infused donors. In both groups there was glycogen degradation during periods of cold preservation, anoxic rewarming, and after reperfusion with portal blood. Degradation rates were greater in the glucose-infused group than in controls in all three periods (p less than 0.05). Despite wide variation in postoperative aspartate aminotransferase (AST) levels among recipients in both groups, the difference in peak postoperative AST levels approached significance (p = 0.06). In addition, peak AST levels were closely correlated to anoxic rewarming time in both groups, but the slope of the relationship was much lower (3834 versus 734, p less than 0.01) in the glucose-infused group. Thus at anoxic rewarming times over 90 minutes, glycogenation was protective of liver function. Peak postoperative AST was significantly correlated to glycogen degradation in the cold preservation and rewarming periods in the glucose-infused group only. Intraoperative glucose infusions in humans can reglycogenate the liver, increase glycogen degradation, and improve certain outcome measures in liver transplantation. PMID- 1417174 TI - Selective shunt in the management of variceal bleeding in the era of liver transplantation. AB - This study reports the Emory experience with 147 distal splenorenal shunts (DSRS) and 110 orthotopic liver transplants (OLT) between January 1987 and December 1991. The purpose was to clarify which patients with variceal bleeding should be treated by DSRS versus OLT. Distal splenorenal shunts were selected for patients with adequate or good liver function. Orthotopic liver transplant was offered to patients with end-stage liver disease who fulfilled other selection criteria. The DSRS group comprised 71 Child's A, 70 Child's B, and 6 Child's C patients. The mean galactose elimination capacity for all DSRS patients was 330 +/- 98 mg/minute, which was significantly (p less than 0.01) above the galactose elimination capacity of 237 +/- 82 mg/minute in the OLT group. Survival analysis for the DSRS group showed 91% 1-year and 77% 3-year survival, which was better than the 74% 1-year and 60% 3-year survivals in the OLT group. Variceal bleeding as a major component of end-stage disease leading to OLT had significantly (p less than 0.05) poorer survival (50%) at 1 year compared with patients without variceal bleeding (80%). Hepatic function was maintained after DSRS, as measured by serum albumin and prothrombin time, but galactose elimination capacity decreased significantly (p less than 0.05) to 298 +/- 97 mg/minute. Quality of life, measured by a self-assessment questionnaire, was not significantly different in the DSRS and OLT groups. Hospital charges were significantly higher for OLT (median, $113,733) compared with DSRS ($32,674). These data support a role for selective shunt in the management of patients with variceal bleeding who require surgery and have good hepatic function. Transplantation should be reserved for patients with end-stage liver disease. A thorough evaluation, including tests of liver function, help in selection of the most appropriate therapeutic approach. PMID- 1417175 TI - Is portal-systemic shunt worthwhile in Child's class C cirrhosis? Long-term results of emergency shunt in 94 patients with bleeding varices. AB - A prospective evaluation was conducted of 94 unselected patients ("all comers") with biopsy-proven Child's class C cirrhosis (93% alcoholic) and endoscopically proven acutely bleeding esophageal varices who underwent emergency portacaval shunt (EPCS) (85% side-to-side, 15% end-to-side) within 8 hours of initial contact (mean, 6.1 hours) during the past 12 years. Follow-up has been 100% and includes all patients for at least 1 year, and 61 patients (65%) for 5 to 12 years. Incidence of serious risk factors on initial contact was: ascites, 97%; jaundice, 86%; portal-systemic encephalopathy including past history, 71%; severe muscle wasting, 96%; alcohol ingestion within 7 days, 66%; delirium tremens, 16%; serum albumin, less than or equal to 2.5 g/dL 76%; indocyanine green dye retention greater than or equal to 50% in 45 minutes, 66%; serum glutamic oxaloacetic transaminase greater than or equal to 100 units/L, 60%; hyperdynamic cardiac output greater than or equal to 6 L/minute, 98%. Mean Child's point score was 13.7 out of a maximum of 15. EPCS reduced mean corrected free portal pressure from 286 to 23 mm saline, and permanently controlled variceal bleeding in every patient. Of the 94 patients, 74 (80%) left the hospital alive and 68 (72%) survived 1 year. Five-year actuarial survival rate is 64%. Hepatic failure was the main cause of death during initial hospitalization as well as during follow up, when it was related to continued alcoholism. Portal-systemic encephalopathy, which was present on initial contact in 55% of patients, occurred at some time during follow-up in 18.7%, but was recurrent and required dietary protein restriction in only 9%, all of whom had resumed alcoholism. The low incidence of portal-systemic encephalopathy was attributable to the lifelong program of follow up with regular dietary counseling and continued emphasis on both protein restriction to 60 g/day and abstinence from alcohol. Abstinence was sustained in 69%, liver function improved in 82%, general health was judged excellent or good in 73%, and Child's risk class converted to class B in 73% and class A in 21%. Excluding retirees because of age, 42% were gainfully employed or engaged in full time housekeeping. Long-term shunt patency was documented in 100% of survivors by yearly angiography or Doppler ultrasonography. It is concluded that EPCS within 8 hours of initial contact permanently controls variceal hemorrhage and results in prolonged survival and a life of acceptable quality in many alcoholic cirrhotic patients in Child's class C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1417176 TI - Results of surgery on 6589 gastric cancer patients and immunochemosurgery as the best treatment of advanced gastric cancer. AB - Results of 6589 gastric cancer operations at the Department of Surgery, Seoul National University Hospital, from 1970 to 1990 were reported. About two thirds (76.6%) were advanced gastric cancer (stages III and IV). The 5-year survival rate of operated stage III gastric cancer was only 30.6%, with frequent recurrence. Conversely, cell-mediated immunities of advanced gastric cancer patients were significantly decreased. Therefore, to improve the cure rate and to prevent or delay recurrence, curative surgery with confirmation of free resection margins and systematic lymph node dissection of perigastric vessels were performed and followed by early postoperative immunotherapy and chemotherapy (immunochemosurgery) in stage III patients. To evaluate the effect of immunochemosurgery, two randomized trials were studied in 1976 and 1981. In first trial, 5-fluorouracil, mitomycin C, and cytosine arabinoside for chemotherapy and OK 432 for immunotherapy were used. The 5-year survival rates for surgery alone (n = 64) and immunochemosurgery (n = 73) were 23.4% and 44.6%, respectively, a significant difference. In the second trial, there were three groups: group I, immunochemosurgery (n = 159); group II, surgery and chemotherapy (n = 77); and group III, surgery alone (n = 94). 5-Fluorouracil and mitomycin C for chemotherapy and OK-432 for immunotherapy were administered for 2 years. The 5 year survival rate of group I was 45.3%, significantly higher than the 29.8% of group II and than the 24.4% of group III. The postoperative 1-chloro-2.4 dinitrobenzene test, T-lymphocyte percentage, phytohemagglutinin- and con-A stimulated lymphoblastogenesis and the antibody-dependent cell-mediated cytotoxicity test showed more favorable values in the immunochemosurgery group. Therefore, immunochemosurgery is the best multimodality treatment for advanced gastric cancer. PMID- 1417178 TI - Thoracoscopic esophagomyotomy. Initial experience with a new approach for the treatment of achalasia. AB - The authors treated 17 patients with achalasia by a thoracoscopic (15 patients) or laparoscopic (2 patients) Heller myotomy. All patients had dysphagia and an upper gastrointestinal series demonstrating a dilated esophagus with a bird-beak deformity at the cardia. Manometry showed a mean lower esophageal sphincter (LES) pressure of 32 +/- 4 mmHg, incomplete sphincter relaxation on swallowing, and no primary esophageal peristalsis. After operation, mean LES pressure was 10 +/- 2 mmHg. Fifteen patients were fed on the second postoperative day. The average hospital stay was 3 days, and there were no deaths or major complications. In three early patients, the myotomy was not carried far enough onto the stomach, and dysphagia persisted until a second myotomy was performed (laparoscopically in two patients). The authors found that having an endoscope in the esophagus during the operation facilitated exposure and was vital to determine the appropriate length of the myotomy. With regard to dysphagia, final results were excellent in 12 patients (70%), good in two patients (12%), fair in two patients (12%), and poor in one patient (6%). Heller myotomy can be safely and reliably performed with minimally invasive techniques. Dysphagia is relieved, postoperative pain is minimal, hospital stay is short, and the patient can return quickly to normal activity. PMID- 1417177 TI - Growth hormone and insulin reverse net whole body and skeletal muscle protein catabolism in cancer patients. AB - The authors examined the effect of recombinant-human growth hormone (r-hGH) and insulin (INS) administration on protein kinetics in cancer patients. Twenty-eight cancer patients either received r-hGH for 3 days (GH group, n = 12, weight loss = 6 +/- 2%) or were not treated (control [CTL] group, n = 16, weight loss = 11 +/- 2%) before metabolic study. Recombinant-human growth hormone dose was 0.1 mg/kg/day (n = 6) or 0.2 mg/kg/day (n = 6). Patients then underwent measurement of baseline protein kinetics (GH/B, CTL/B) followed by a 2-hour euglycemic insulin infusion (1 mU/kg/minute) and repeat kinetic measurements (GH/INS,CTL/INS). Whole-body protein net balance (mumol leucine/kg/minute) was higher (p less than 0.05) in GH/INS (0.20 +/- 0.06) than in CTL/INS (0.06 +/- 0.03) or GH/B (-0.19 +/- 0.03). Skeletal muscle protein net balance (nmol phenylalanine/100 g/minute) in GH/INS (25 +/- 6) and CTL/INS (19 +/- 5) was higher than CTL/B (-18 +/- 3). Recombinant-human growth hormone and insulin reduce whole-body and skeletal muscle protein loss in cancer patients. Simultaneous use of these agents during nutritional therapy may benefit the cancer patient. PMID- 1417180 TI - Strategies in the surgical treatment of malignant ventricular arrhythmias. An 8 year experience. AB - Introduction of the automatic implantable cardioverter defibrillator (AICD) has dramatically affected the surgical treatment of malignant ventricular tachyarrhythmias. The authors continue to perform electrophysiologically directed subendocardial resection (SER) of left ventricular (LV) scars in selected patients, and we revascularize (CABG) those patients undergoing AICD implantation who have significant myocardial ischemia. In an attempt to define the optimal role of each procedure, this report analyzes our 8-year experience with 348 consecutive patients treated surgically for these arrhythmias (SER since 1983 and AICD since 1986). All patients undergoing SER had organized ventricular tachycardia (VT) as a result of myocardial infarction, and most had LV aneurysms; of those undergoing AICD or AICD/CABG, 60% had VT, 15% had ventricular fibrillation, and 25% had both or were noninducible. The thirty-day mortality rate was 1.5% (3/197) for AICD, 5.4% (5/93) for AICD/CABG, and 8.6% (5/58) for SER; these mortality figures are not significant different. Late deaths in all groups were predominantly due to congestive heart failure, and actuarial survival as well as freedom from sudden death was similar between the groups at 4 years. Recurrent VT occurred in 167 of 282 (59%) of long-term survivors of AICD or AICD/CABG during follow-up and in nine of 53 (17%) of those with SER. Forty-eight per cent of survivors of AICD or AICD/CABG required antiarrhythmic medications, whereas only 11% of those with SER required antiarrhythmics. Long-term survival in each group is much higher than that reported for comparable patients with severe LV dysfunction treated medically. In those patients with organized VT and LV aneurysm who are judged able to survive the procedure, SER offers a high likelihood of cure rather than simple prevention of sudden death. PMID- 1417179 TI - Transforming growth factor (TGF)-beta stimulates hepatic jun-B and fos-B proto oncogenes and decreases albumin mRNA. AB - Transforming growth factor-beta (TGF-beta) modulates some components of the acute phase response in hepatic cells. The mechanisms for these actions of TGF-beta are largely unknown. The authors recently found that the decrease in albumin mRNA after TGF-beta 1 treatment required de novo RNA and protein synthesis, suggesting that TGF-beta acts through induction of another gene. The purpose of the current study was to determine whether TGF-beta 1 could regulate the expression of both the jun and fos genes that encode transcriptional regulatory proteins that constitute the AP-1 complex, and to determine whether expression of these genes may be coordinated with the decrease in albumin mRNA. Northern blot hybridization was used to determine levels of specific mRNAs. Transforming growth factor-beta 1 increased the levels of both jun-B and fos-B mRNA by 60 minutes after treatment of mouse hepatoma (BWTG3) cells. When TGF-beta 1 was removed from the media after 4 hours, there was a sustained effect of increased jun-B and decreased albumin mRNA (greater than 48 hours), and the subsequent decrease in jun-B levels coincided with the increase in albumin mRNA. The tumor-promoting phorbol ester (phorbol 12-myristate 13-acetate [PMA]), known to induce jun and fos gene expression, caused increases in jun-B and fos-B that preceded the decrease in albumin mRNA levels at 24 hours. These observations are consistent with our hypothesis that jun-B and fos-B induction may participate in downregulation of albumin synthesis as well as other hepatic responses to TGF-beta. PMID- 1417181 TI - Surgical management of dysrhythmias in infants and small children. AB - Surgery for cardiac dysrhythmias is infrequently reported in infants and children as compared with adults. This report reviews 55 infants and small children (age, less than or equal to 5 years) operated on during the interval July 1, 1984 to December 31, 1991 for Wolff-Parkinson-White Syndrome (41), atrioventricular node reentry (two), atrial automatic tachycardia (two), and ventricular tachycardia (nine). Ages ranged from 3 weeks to 71 (mean, 29) months. Associated congenital heart defects were present in five (10%). Indications for surgery included failure of medical therapy, life-threatening dysrhythmias, and more recently, failure of catheter ablation. There were no hospital or late deaths. One patient sustained perioperative central nervous system injury. Surgery was successful in 52 of 55 (94.5%) (Wolff-Parkinson-White, 38/41 (93%); atrioventricular node reentry, 2/2 (100%); atrial automatic tachycardia, 3/3 (100%); ventricular tachycardia, 9/9 (100%). Ventricular function returned to normal in all 12 patients in whom it was abnormal before operation. Thus, surgical ablation is highly successful in the management of various forms of refractory or life threatening dysrhythmias in infants and small children. Catheter ablation techniques require significant fluoroscopic time, are more difficult in infants, and as yet do not have adequate long-term follow-up. Accordingly, surgery may continue to play a role in this particular group of patients. PMID- 1417182 TI - Smooth muscle cell elastase, atherosclerosis, and abdominal aortic aneurysms. AB - Smooth muscle cells (SMC) were obtained by outgrowth of human aortic explants from abdominal aortic aneurysm (AAA) patients, aortic occlusive disease (AOD) patients, and transplant donors (controls). Specimens were incubated with medium alone or medium with either elastin-derived peptides (EDP, 5 micrograms/mL) or low-density lipoproteins (LDL, 5 micrograms/mL). Elastase activity (ng/mg total protein) was assayed from 4-week-old cultures. Control aortas obtained from patients significantly younger secrete an increased amount of elastase at baseline compared with AOD and AAA patients (p less than 0.05). Elastin-derived peptides caused a significant increase in elastase secretion in all groups. The increase in elastase secretion in response to EDP in AAA patients was significantly higher compared with AOD or control. Low-density lipoprotein had no effect on SMC elastase secretion. These data suggest that (1) aortic SMCs secrete elastase in response to EDP, (2) SMC elastase is age dependent, and (3) AAA SMC secrete an abnormally high amount of elastase compared with AOD and control aortas in response to EDP. Like the neutrophil, the SMC is highly responsive to the degradation products of elastin and in AAA patients secrete significantly increased amounts of elastase in response to the breakdown products of atherosclerosis. PMID- 1417184 TI - Biliary strictures complicating liver transplantation. Incidence, pathogenesis, management, and outcome. AB - Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation. PMID- 1417183 TI - Long-term surgical results in sudden death syndrome associated with cardiac dysfunction after myocardial infarction. AB - To evaluate the surgical results in patients with inducible ventricular tachyarrhythmias due to coronary disease and left ventricular dysfunction, the authors reviewed their experience in 170 patients who had survived one or more cardiac arrests after myocardial infarction and were unresponsive to drug therapy based on electrophysiologic studies (EPS). There were nine operative deaths (5%). Based on intraoperative EPS, surgical remodeling of left ventricular dysfunction (aneurysm resection, infarct debulking, and septal reinforcement) with map-guided cryoablation and coronary artery bypass graft was performed in 34 patients (group A), and left ventricular remodeling and coronary artery bypass graft without guided endocardial resection was performed in 25 patients (group B). Forty-three patients (group C) had coronary artery bypass graft with implantation of an automatic implantable cardioverter defibrillator (AICD). Group D (68 patients) received AICD only. After operation, based on EPS results, four patients in group A (12%) and three patients in Group B (15%) required AICD implantation. Overall survival at 6 years was 65%, 48%, 85%, and 58% in patient groups A, B, C, and D, respectively (p = not significant). During follow-up in group A patients, none died suddenly and none needed AICD. In group B, two patients required AICD 3 and 5 years later, and five patients died suddenly. The incidence of sudden death was 2.3%/patient/year and 3.5%/patient/year after AICD implantation (groups C and D). At 6 years, cardiac-event-free survival was 80% and 70% for groups A and B and 38% and 24% for groups C and D, respectively (p less than 0.001). Patients receiving map-guided ablative procedures had significantly improved cardiac-event free survival rates. PMID- 1417185 TI - Pulmonary autograft replacement in children. The ideal solution? AB - Fifty-one children, aged 1.8 to 21 years (mean, 11.4) with aortic valve replacement using a pulmonary autograft are reviewed. Twenty-nine were intra aortic implants and 22 were root replacements. There was one operative death, no late deaths, and two have required reoperation. Actuarial freedom from reoperation was 93% +/- 5.5 at 5.6 years. Freedom from progression of aortic insufficiency (AI) was 81% +/- 9 at 5.6 years in the intra-aortic implants and 86% +/- 10 in the root replacement. Enlargement of the pulmonary autograft was seen echocardiographically in both groups. This enlargement was consistent with somatic growth and not associated with progression of AI. Ten of 19 patients with aortic stenosis had an LV mass index suggestive of LV hypertrophy before operation. At 1 year, 18 of 25 had a normal LV mass index. Thirteen of 16 patients with AI had preoperative abnormal LV mass index. All but four returned to normal by 1 year. Low operative risk, excellent function, resolution of abnormal LV hemodynamics, and enlargement consistent with somatic growth suggest that the pulmonary autograft is the ideal replacement for the malfunctioning aortic valve. PMID- 1417186 TI - Adherent neutrophils mediate permeability after atelectasis. AB - Re-expansion of atelectatic lung is associated with increased permeability. This study tests whether neutrophils mediate this event. Right middle lobar atelectasis was induced in anesthesized rabbits (n = 18) by intraluminal obstruction of the bronchus after a 20-minute ventilation with 100% O2. After 1 hour of bronchial obstruction and 20 minutes after lobar re-expansion, leukopenia was noted, 2870 +/- 210 white blood cells (WBC)/mm3, relative to control animals treated with a noninflated balloon catheter, 6500 +/- 410 WBC/mm3 (p less than 0.05). Three hours after re-expansion, neutrophils were sequestered in the previously atelectatic region 78 +/- 7 polymorphonuclear leukocytes (PMN)/10 high power field (HPF), as well as in nonatelectatic areas, 40 +/- 3 PMN/10 HPF, higher than control values of 26 +/- 3 PMN/10 HPF (p less than 0.05). In the atelectatic region, neutrophil sequestration was associated with increased protein concentration in lobar bronchoalveolar lavage (BAL) of 1370 +/- 100 micrograms/mL, higher than control values of 270 +/- 20 micrograms/mL (p less than 0.05). Reexpansion also induced increases in lung wet-to-dry weight ratio (W/d) of 6.2 +/- 0.2, higher than control values of 4.3 +/- 0.1 (p less than 0.05). Rendering rabbits neutropenic (n = 18) (0 to 4 PMN/mm3) limited the atelectasis-induced protein accumulations in BAL (520 +/- 60 micrograms/mL) and increase in lung W/d (5.2 +/- 0.1) (both p less than 0.05). Intravenous (I.V.; treatment of another group (n = 18) with an anti-CD 18 monoclonal antibody (R 15.7, 1 mg/kg) before balloon deflation prevented leukopenia (6550 +/- 560 WBC/mm3), minimized neutrophil sequestration (36 +/- 2 PMN/10 HPF), and attenuated protein leak (710 +/- 95 micrograms/mL) and the increased lung W/d (5.6 +/- 0.1) (all p less than 0.05). A final atelectatic group (n = 9) was treated I.V. with the anti-intercellular adhesion molecule-1 monoclonal antibody (RR 1/1, 1 mg/kg), which also prevented leukopenia and showed similar protection of microvascular barrier function. These data indicate that adherent neutrophils in large part mediate lung permeability and edema after atelectasis and re expansion. Adhesion receptors of both neutrophils and endothelial cells regulate this event. PMID- 1417187 TI - Muscle protein breakdown during endotoxemia in rats and after treatment with interleukin-1 receptor antagonist (IL-1ra). AB - The purpose of this study was to examine the effect of endotoxemia on muscle protein degradation and to test the hypothesis that muscle proteolysis during endotoxemia is regulated by interleukin-1 (IL-1). Both total and myofibrillar protein breakdown rates in incubated extensor digitorum longus muscles were increased after the subcutaneous injection of 0.1 or 1.0 mg/kg endotoxin in rats. The endotoxin-induced increase in muscle protein breakdown was blunted by IL-1 receptor antagonist, administered intraperitoneally at a total dose of 45 or 105 mg/kg. Results suggest that endotoxemia in rats gives rise to sepsislike changes in muscle protein breakdown. Increased muscle protein breakdown during endotoxemia may be regulated, at least in part, by IL-1. PMID- 1417188 TI - Women in the POSCH trial. Effects of aggressive cholesterol modification in women with coronary heart disease. The POSCH Group. Program on the Surgical Control of the Hyperlipidemias. AB - The Program on the Surgical Control of the Hyperlipidemias (POSCH) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infarction. In POSCH, 78 of the 838 patients (9.3%) were women, with 32 randomized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group. At 5 years, the mean per cent change from baseline was -23.9% for total plasma cholesterol (p < 0.0001), -36.1% for low-density lipoprotein cholesterol (p < 0.0001), and +8.5% for high-density lipoprotein cholesterol (p = not significant). Because of the small number of women, no statistically significant changes in clinical event rates were observed between the control and the surgery groups. A comparison of 162 coronary arteriography film pairs in the POSCH women, between baseline and 3, 5, 7, and 10 years, consistently showed less disease progression in the surgery group (p = 0.013 for combined assessments of the baseline to the longest follow-up film). Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men, and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates, we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression. The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women. PMID- 1417189 TI - The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores. AB - The first randomized, blinded, placebo-controlled human trials of recombinant basic fibroblast growth factor (bFGF) for pressure sore treatment were performed. Three different concentrations of bFGF in five dosing schedules were tested for safety using hematology, serum chemistries, urinalysis, absorption, antibody formation, and signs of toxicity. Efficacy was evaluated by wound volumes, histology, and photography. No toxicity, significant serum absorption, or antibody formation occurred. In six of eight subgroups, there was a trend toward efficacy with bFGF treatment. When all subgroups were combined, comparison of the slopes of the regression curves of volume decrease over initial pressure sore volume demonstrated a greater healing effect for the bFGF-treated patients (p < 0.05). Histologically, bFGF-treated wound sections demonstrated increased fibroblasts and capillaries. More patients treated with bFGF achieved > 70% wound closure (p < 0.05). Blinded observers were able to distinguish differences in visual wound improvement between bFGF and placebo groups. These data suggest that bFGF may be effective in the treatment of chronic wounds. PMID- 1417190 TI - Intrathymic injection of donor alloantigens induces donor-specific vascularized allograft tolerance without immunosuppression. AB - The induction of donor-specific tolerance could prevent the side effects of immunosuppression while improving allograft survival. Male adult Buffalo (RT1b) rats underwent an intrathymic (IT), portal venous (PV), intrasplenic (IS), or subcutaneous (SQ) injection of 25 x 10(6) major histocompatibility complex (MHC) mismatched Lewis (RT1(1)), UV-B-irradiated Lewis (RT1(1)), ACI (RT1a), or syngeneic Buffalo (RT1b) splenocytes. At the completion of the donor alloantigen injection, 1 mL rabbit anti-rat lymphocyte serum (ALS) was administered intraperitoneally to the Buffalo recipients, and 21 days later a heterotopic Lewis or ACI heart was transplanted. Intrathymic injection of donor alloantigen induced a donor-specific tolerance that allowed the cardiac allograft to survive indefinitely (mean survival time [MST] > 140.7 days) in 84% of the recipients without further immunosuppression, whereas groups receiving antigen injections at other sites (PV, IS, and SQ) plus ALS rejected cardiac allografts in normal fashion (MST approximately 8.0 days). Buffalo recipient rats with long-term surviving Lewis cardiac allografts after Lewis IT injection and ALS subsequently rejected a heterotopic third-party ACI cardiac allograft in normal fashion (MST approximately 7 days), whereas a second Lewis cardiac allograft was not rejected (MST > 116 days). Microchimerism is unlikely because Lewis allograft survival was also prolonged (MST > 38.7 days) in rats receiving UV-B-irradiated splenocytes IT, which cannot proliferate. Survival of Lewis renal allografts was also prolonged, but not indefinitely, in Buffalo recipients possessing a long-term surviving Lewis cardiac allograft (MST approximately 17.6 days versus 7 days for control). This model emphasizes the potential role of exposure of immature thymocytes to foreign donor alloantigens during maturation in the thymic environment for the development of unresponsiveness to an MHC-mismatched donor specific vascularized allograft. PMID- 1417191 TI - Intestinal radioprotection by two new agents applied topically. AB - The purpose of this study was to test two novel antioxidant drugs, each capable of inhibiting membrane peroxidation and of free radical scavenging, as topical radioprotectants for the intestine. A loop of rat midintestine was exteriorized and radiated while the remainder of the animal was protected in a lead box. The intestine was first compartmentalized and each segment filled with a test solution. Radiated segments of intestine were compared, drug filled with vehicle filled, and both with normal unradiated intestine. The animals were killed 5 days after 1100 cGy radiation to the exteriorized loop. Crypt numbers and mucosal height were used as the measures of injury protection. On the basis of crypt numbers, the 21-amino steroid (U-74500A) gave approximately 40% and the vitamin E like compound (U-78518F) gave 60% reduction in crypt loss. The authors conclude that lumenal antioxidant drugs can provide partial protection of the intestinal mucosa from acute radiation damage and that these two specific agents are effective and potentially useful. PMID- 1417192 TI - Surgical treatment of tumors of the distal rectum with sphincter preservation. AB - One hundred one patients with villous adenoma or invasive carcinoma of the distal rectum treated with local excision or coloanal anastomosis were studied. Twenty three (45%) of the 51 patients with villous adenomas had transanal excision, another 23 (45%) had a posterior proctotomy, and five (10%) had a coloanal anastomosis. Only two patients with a villous adenoma developed a recurrence requiring repeat local excision. Fifteen (30%) of the 50 patients with invasive cancer were treated by transanal excision. All had tumors confined to the submucosa or superficial muscularis. Eighteen (85%) of 21 patients having posterior proctotomy also had tumors with similar depth of invasion. Six (43%) of the 14 patients having coloanal anastomosis had Dukes' B tumors, six (43%) were Dukes' C, and another two (14%) underwent palliative resection. The overall actuarial 5-year survival was 77%. Only four patients treated by transanal excision or posterior proctotomy died of metastatic disease. In the coloanal group, two of 12 patients undergoing curative resection died of recurrent cancer, and another has a pelvic recurrence. Villous adenomas of the distal rectum and selected carcinomas may be treated with local excision and coloanal anastomosis with preservation of sphincter function with good results. PMID- 1417194 TI - High-level expression of recombinant human tPA in cultivated canine endothelial cells under varying conditions of retroviral gene transfer. AB - Successful genetic transduction of endothelial cells (EC) provides a theoretic means of increasing luminal secretion of tissue-type plasminogen activator (tPA) and lessening arterial and venous thrombotic processes. To identify the duration and number of retroviral exposures for an optimal tPA expression, enzymatically derived adult canine jugular venous EC were subjected to different exposure regimens using an amphotropic murine retroviral vector, MFG, containing the human tPA gene. Human tPA antigen secretion and its functional activity were determined at 2 days (subconfluent cells) and 14 days (confluent cells) after retroviral exposure. High-level secretion of human tPA was detected among transduced EC in all experimental groups. No secretion of human tPA occurred in control EC exposed to media alone. At 2 days after transduction, no significant differences in tPA secretion rates occurred among the different exposure regimens. At 14 days, the 12-hour X two-exposure group exhibited higher tPA secretion rates than all other exposure regimens (analysis of variance, p < 0.05). All exposure groups at 14 days exhibited significantly higher tPA secretion compared with those at 2 days (analysis of variance, p < 0.05). The presence of retroviral sequences in the genome of transduced EC was confirmed by Southern blot analysis. At 14 days, increased EC numbers were observed in vector-exposed wells compared with controls. Human tPA functional activity paralleled tPA antigen secretion. Genetically modified canine EC are capable of high levels of constitutive expression of human tPA after relatively short exposures to a retroviral vector containing the reporter gene. Increased cell number of tPA-transduced EC in culture suggests that tPA also may have other biologically important effects. These results support the efficacy of MFG-tPA gene transfer as a means of genetically modifying EC fibrinolytic activity and establishes the potential of this technology in vivo. PMID- 1417193 TI - The degree of bacterial translocation is a determinant factor for mortality after burn injury and is improved by prostaglandin analogs. AB - Bacterial translocation and related mortality rates were examined in previously transfused BALB/c mice that were gavaged with 14C radioisotope-labeled Escherichia coli before inflicting a 20% full-thickness flame burn. Radionuclide counts were measured in blood obtained by retro-orbital puncture 4 hours postburn, and survival was recorded for 10 days. Radionuclide counts in the blood correlated well with both radionuclide counts and numbers of viable bacterial in the tissues. Survivors had significantly less bacterial translocation as evidenced by blood radionuclide counts compared with nonsurvivors, and there was a significant inverse correlation between the degree of translocation and the length of survival. In the next experiment, the prostaglandin E (PGE) analogs misoprostol, enisoprost, or 16,16-dimethyl PGE2 were administered to transfused animals for 3 days before burn. Prostaglandin E analogs significantly reduced bacterial translocation as measured by blood radionuclide counts 4 hours postburn and improved survival. The data demonstrate that the intensity of bacterial translocation after burn injury is significantly associated with subsequent death. Improvement of survival by PGE analogs is associated with decreased bacterial translocation. PMID- 1417195 TI - Delayed surgical repair and ECMO improves survival in congenital diaphragmatic hernia. AB - One hundred ten infants with congenital diaphragmatic hernia (CDH) developed life threatening respiratory distress in the first 6 hours of life. Associated anomalies were present in 33%. Twenty-eight of 65 infants (43%) treated before 1987 (pre-extracorporeal membrane oxygenation [ECMO] era) survived after immediate CDH repair, and mechanical ventilation with or without pharmacologic support. Only two of 16 (12.5%) infants requiring a prosthetic diaphragmatic patch survived. Since 1987, 31 of 46 (67.4%) infants with birth weight, gestational age, and severity of illness similar to the pre-1987 group survived. All patients were immediately intubated and ventilated. Seven (four with lethal chromosomal anomalies) infants died before treatment, and 30 stabilized (partial pressure of carbon dioxide [PCO2] < 50; partial pressure of oxygen [PO2] > 100; pH > 7.3) and underwent delayed CDH repair at 5 to 72 hours. Fifteen did well on conventional support and survived. Fifteen infants deteriorated after operation: 11 were placed on ECMO with eight survivors, and four infants were not considered ECMO candidates. Nine babies failed to stabilize initially and were placed on ECMO before CDH repair (alveolar-arterial gradient > 600 and oxygenation index > 40), and seven survived. The overall survival rate was 80% at 3 months in this ECMO-treated group. Early mortality was due to inability to wean from ECMO (one), intracranial hemorrhage (one), liver injury (one), and pulmonary hypoplasia (one). Nine of 11 babies requiring a prosthetic patch in the post-1987 ECMO group survived (81.8%). There were three late post-ECMO deaths (3 to 18 months) of right heart failure (two) and sepsis (one). Symptomatic gastroesophageal reflux occurred in nine cases, six requiring a fundoplication in the bypass babies. Recurrent diaphragmatic hernia occurred in nine cases (five ECMO). The overall survival rate was significantly improved in the delayed repair/ECMO group (67% versus 43%; p < 0.05) and was most noticeable in infants requiring a prosthetic diaphragm (81.2% versus 12.5%; p < 0.005). These data indicate that early stabilization, delayed repair, and ECMO improve survival in high-risk CDH. Early deaths are related to pulmonary hypertension and can be reversed by ECMO. PMID- 1417196 TI - Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. AB - A new polyvalent melanoma cell vaccine (MCV) was administered to 136 stage IIIA and IV (American Joint Committee on Cancer) melanoma patients. Induction of cell mediated and humoral immune responses to common melanoma-associated antigens present on autologous melanoma cells was observed in patients receiving the new MCV. This was accompanied by increased activation of tumor-infiltrating lymphocytes. Survival correlated significantly with delayed cutaneous hypersensitivity (p = 0.0066) and antibody responses to MCV (p = 0.0117). Of 40 patients with evaluable disease, nine (23%) had regressions (three complete). From our historical database of 126 stage IIIA and 1275 stage IV melanoma patients, there were no significant changes in the natural history of metastatic melanoma during the past 20 years. Univariate and multivariate analyses demonstrated prognostic significance for site of metastases (p = 0.0001) and immunotherapy with the new MCV (p = 0.0001). Overall our new MCV increased the median and 5-year survival of stage IIIA melanoma patients with regional soft tissue metastases twofold (p = 0.00024), and stage IV patients threefold (p = 0.0001) compared with previous immunotherapy and other treatments. PMID- 1417197 TI - Long-term intraperitoneal insulin delivery. AB - Over the past 5 years, 21 patients with insulin-dependent diabetes mellitus have been managed at the Johns Hopkins Medical Institutions with variable rate, remotely controlled implanted insulin pumps. To date, nearly 70 patient-years of experience has been gained with intraperitoneal delivery of a new U-400 insulin with a surfactant. All 21 patients are alive after a mean of 39.3 months (range, 10 to 65 months) after insulin pump implantation. Nineteen of the 21 patients remain on intraperitoneal insulin, for a 5-year actuarial system survival of 90%. Glucose control was improved, especially during the first 16 months after pump implantation, without an increased incidence of severe hypoglycemia. Catheter blockage has been a significant problem, occurring in nine of the 21 patients (43%). Catheter occlusion has been successfully managed, however, with laparoscopic repair in seven of 10 attempts or with catheter change in four of five patients. Nevertheless, quality of life and patient acceptance remain excellent. Moreover, pre-existing nephropathy, neuropathy, and retinopathy have been surprisingly stable. With an aggressive policy of catheter change or laparoscopic clearance of catheter blockage, long-term intraperitoneal insulin delivery is now a safe and effective treatment for type I diabetics. PMID- 1417198 TI - Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma. AB - The authors reviewed their institutional experience with liver resection for metastatic colorectal carcinoma to (1) determine whether perioperative blood transfusion affects survival; (2) identify prognostic determinants; and (3) estimate the patient requirement for a prospective randomized trial designed to demonstrate efficacy of liver resection. Two hundred eighty consecutive patients treated by potentially curative liver resection between 1960 and 1987 were included. Data were obtained for all but 10 patients for at least 5 years after operation or through 1990. Actuarial survival curves related to potential prognostic determinants were analyzed with the log-rank test. Overall, survival was 47 +/- 3% at 3 years and 25 +/- 3% at 5 years, including 4% 60-day operative mortality rate. Eighty-one patients who did not receive blood 7 days before to 14 days after operation had 60 +/- 6% 3-year and 32 +/- 6% 5-year survival compared with 40 +/- 4% and 21 +/- 3% survival rates for 183 patients who received at least one unit (p = 0.03, operative deaths excluded). Extrahepatic disease (p = 0.015), extrahepatic lymph node involvement (p = 0.002), satellite configuration of multiple metastases (p = 0.0052), and initial detection by abnormal liver enzymes (p = 0.0005) were associated with poor survival rates. Synchronous presentation of metastatic and stage B primary disease was associated with a favorable prognosis (p = 0.003). The requirement for a prospective randomized trial estimated by an exponential survival model would be 36, 74, 168, or 428 patients if 5-year survival without resection were 1, 5, 10, or 15%. We conclude that (1) perioperative blood transfusion may be adversely associated with survival; (2) extrahepatic disease, extrahepatic lymph node involvement, satellite configuration, and initial detection by clinical examination or a liver enzyme abnormality portend a poor prognosis; and (3) a prospective randomized trial of liver resection is impractical because of the large patient requirement, at least by a single institution. PMID- 1417199 TI - RS-61443 (mycophenolate mofetil). A multicenter study for refractory kidney transplant rejection. AB - RS-61443 (mycophenolate mofetil) inhibits a key enzyme of the de novo synthesis of purine nucleotides in T and B lymphocytes. The purpose of this study was to evaluate the efficacy of RS-61443 in patients with refractory renal allograft rejection. Patients eligible for the study had previously undergone anti rejection therapy with high-dose steroids or OKT3 monoclonal antibody. All rejection episodes were proven by renal biopsy. Successful rescue was achieved in 52 (69%) patients. Rescue was more successful when patients were entered with a creatinine of 4 mg/dL or lower (79%), versus a 52% rescue rate in patients entered with a creatinine of 4 mg/dL or above. Major side effects were predominantly gastrointestinal, but there was no overt nephrotoxicity, hepatotoxicity, or bone marrow suppression. The overall infection rate was 40%, with the spectrum of infections characteristic for the highly immunocompromised patient. The conclude that this pilot study suggests that RS-61443 is effective in refractory kidney allograft rejection. Based on this study, prospectively randomized multi-center trails have been planned and are in progress. PMID- 1417200 TI - Plasmodium falciparum: effect of chloroquine, halofantrine and pyrimethamine on the infectivity of gametocytes for Anopheles stephensi mosquitoes. AB - The activity of chloroquine, halofantrine and pyrimethamine against the gametocytes and sporogonic stages of Plasmodium falciparum (strain NF54) was tested. Five-day-old gametocytes (stages I and II) from in vitro cultures were exposed to the drugs for 48 hours. The effect of the drugs on gametocyte development was assessed by counting gametocytes on days nine and 15 of culture and determining the infectivity of the drug-treated gametocytes to mosquitoes. Gametocytogenesis was partially inhibited by all three drugs; there were 71% of the number of gametocytes in drug-free control cultures in cultures with 3 x 10( 8) M chloroquine, 51% with 5 x 10(-8) M chloroquine, 78% with 5-7 x 10(-9) M halofantrine, and 48% with 10(-7) M pyrimethamine. Halofantrine- and pyrimethamine-treated gametocytes were found to be more infective to Anopheles stephensi than untreated controls. The three drugs were also administered to the mosquitoes, either in the first bloodmeal, which contained gametocytes from in vitro cultures, or in the second, parasite-free bloodmeal, given four days after infection. The sporontocidal activity of the drugs was evaluated by counting the number of oocysts on the midgut seven or eight days after infection, or the number of sporozoites in the salivary glands 15 days after infection. A sporontocidal effect was observed only when pyrimethamine was administered with the infective bloodmeal. Neither chloroquine nor halofantrine had any marked effect on sporogony at the concentrations tested. PMID- 1417201 TI - Infectivity to the vector Triatoma infestans of dogs infected with Trypanosoma cruzi in north-west Argentina. AB - The influence of reinfections on the infectivity to Triatoma infestans of dogs seropositive to Trypanosoma cruzi was investigated in Amama, north-west Argentina, before (1984) and after (1986-1987) elimination of domestic bugs with residual insecticides in 1985. Infectivity was quantified by the percentage of infected bugs in each xenodiagnosis of a seropositive dog, i.e. the infective force (IF). Exposure to reinfection was represented by the domiciliary density of infected bugs and by an index of the potentially-infective contacts (IPIC) experienced by each dog (calculated as the product of the relative density of bugs per dog, the proportion of infected bugs, and the proportion of bugs taking blood meals from the dog). IF was unrelated to the dog's age or sex, or the level of specific antibodies to T. cruzi. Before vector elimination, the IF of seropositive dogs was significantly associated with both the density of infected bugs and the IPIC. After vector elimination, seropositive dogs resident at houses which had 10-70 infected bugs before spraying showed a higher median IF (67-75%) than those living in houses with zero to eight infected bugs before spraying (47 55%). The age-specific IF of seropositive dogs aged one year or older, recorded before (45-64%) and after (52-56%) the elimination of domestic bugs, did not differ significantly. Our data suggest that the infectivity of seropositive dogs to bugs is modified by previous or current exposure to bug-mediated reinfections, and that this relationship might be irreversible in the short term. PMID- 1417202 TI - Western blot of Entamoeba histolytica antigenic fractions: reactivity analysis with sera from intestinal amoebiasis patients. AB - The reactivity of sera from acute-phase intestinal amoebiasis patients (two weeks evolution) was studied to determine which of the Entamoeba histolytica antigens are most frequently immunogenic. Sera were examined by means of immunoelectrotransferase assay using crude extract of HM1:IMSS E. histolytica trophozoites. Three populations of clinically healthy adults from Mexico, Canada and Germany, with no evidence of parasites in faeces, were used as controls. The frequency of antigen recognition was analysed. In ailing individuals, the bands of 23, 24, 26 and 51 kDa were recognized most frequently (65 and 60%) followed by the 62 kDa band (56%). The combination of some of these bands, namely 3.4, 4.1 and 6.7, with molecular weights of 62, 51 and 24 kDa, increased the recognition frequency of patients to 91.4%. These results constitute a first but important step towards the design of more accurate methods for the successful immunodiagnosis and epidemiology of acute intestinal amoebiasis. PMID- 1417203 TI - Epidemiology of Blastocystis hominis infection in Papua New Guinea: age prevalence and associations with other parasites. AB - A community-based study of Blastocystis and other intestinal parasites in the Asaro Valley, Papua New Guinea showed an extraordinary high prevalence and variety of protozoan infections. Apart from infants, nearly everybody had at least one infection, and the mean number of infections per person was around 2.7. The graph of age-specific prevalence for Blastocystis is similar in shape to those for Entamoeba coli and Endolimax nana, indicating probable similarity in transmission patterns and host response. There was no evidence for pathogenicity of Blastocystis at the community level. Three methods are compared for the measurement of association between infections. Two show strong associations, but these are considered to be the result of parallel age-prevalence curves and environmental factors at the village level. When age- and village-matched pairs were considered, only a weak positive association with E. nana was detectable. PMID- 1417204 TI - A survey of taeniid cestodes in farm dogs in mid-Wales. AB - In 1983-1988, dogs on 315 farms in Powys, mid-Wales, were purged once with arecoline acetarsol and the faecal purges were examined for cestodes. A few dogs were examined by autopsy. Ninety-seven farms had at least one infected dog, and cestodes were found in 161 of the 882 dogs examined. The ovine strain of Echinococcus granulosus was found in 41 dogs on 25 farms. Taenia hydatigena, T. pisiformis, T. multiceps, T. serialis, T. ovis and Dipylidium caninum were recovered from 85, 35, 15, 3, 19 and 29 dogs respectively. The results are compared with those of previous surveys in Powys and in other regions of Wales. PMID- 1417205 TI - The cestodes of foxhounds and foxes in Powys, mid-Wales. AB - Cestodes were found in 129 of 875 foxhounds from 20 packs in Powys, mid-Wales, examined by purging in 1983-1988, in the following order of prevalence: Taenia hydatigena in 57 hounds (6.51%), Echinococcus granulosus in 27 (3.09%), Dipylidium caninum in 25 (2.86%), T. ovis in 14 (1.60%), T. pisiformis in 10 (1.14%), T. serialis in five (0.57%) and T. multiceps in four (0.46%). Of 197 foxes examined by autopsy, 22 harboured cestodes: two (1.02%) had E. granulosus, nine (4.57%) T. polyacantha, eight (4.06%) T. pisiformis, two (1.02%) T. serialis, one (0.51%) D. caninum and one (0.51%) Mesocestoides sp. This is the first definite report of T. polyacantha in British foxes. The results are compared with those of previous surveys in Powys and in other parts of Wales, and the reasons for changes in prevalence are discussed. PMID- 1417207 TI - Cultivation of the third-stage larvae of Necator americanus in vitro. AB - When filariform larvae of Necator americanus, enclosed within the second sheath, were cultured in various semi-defined media, the best larval development was achieved in Waymouth's MB 752/1 with 20% foetal calf serum (FCS). In this medium, most of the filariform larvae cast off the second sheath and developed into third stage larvae with provisional buccal capsules and some larvae developed further; 26% were fourth stage after 49 days of culture. Of several supplements tested, only FCS supported such development and no further development occurred if the medium was further supplemented with human red blood cells, liver extract, intestinal extract or tryptose phosphate broth. Larval development stopped at or before early third stage in Eagle's Basal Medium, F-12, NCTC 135 and L-15, even when these media were supplemented with FCS. PMID- 1417206 TI - Polycystic hydatid disease (Echinococcus vogeli). Treatment with albendazole. AB - Six patients with polycystic hydatid disease (PHD) were treated with 10 mg kg-1 day-1 albendazole. One patient was treated continuously for eight months and another for three months. In three other patients treatment was discontinuous, consisting of a series of at least three 30-day cycles separated by 15 days without treatment. The last patient was treated continuously with 12 mg kg-1 day 1 albendazole for 51 days and then with three 30-day cycles of treatment with 10 mg kg-1 day-1 separated by 15-day drug-free intervals. Follow-up ranged from 10 30 months. Considerable clinical improvement and cyst reduction or disappearance occurred in four patients. Clinical improvement, but no changes in the hepatic alterations detected by computerized tomography, occurred in the other two patients, although a pulmonary cyst disappeared in one of them. Adverse effects were proteinuria, alopecia, leucopenia, itching and discrete elevation in aspartate transaminase, all of them reversed after the end of treatment. These results indicate that albendazole is effective for the treatment of PHD. PMID- 1417208 TI - Studies on environmentally-induced colour variation in Simulium sirbanum (Diptera: Simuliidae) using a portable rearing system. AB - Previous studies on the morphological identification of adult female Simulium damnosum s.l. have involved use of colour characters. To determine the degree to which these qualitative characters are influenced by the physical environment, a portable rearing system was constructed. Wild-caught female flies and flies emerging from pupae maintained at ambient temperatures or above showed entirely pale antennae, fore-coxae, wing-tufts and hairs on the scutellum and ninth abdominal tergite, as is normal for S. sirbanum. Adults reared from larvae at below ambient temperatures were also pale, except for the antennae which were dark in all specimens. Adult females emerging from pupae maintained at below ambient temperatures were entirely pale up to the fourth day of emergence and mostly with dark antennae. The biological significance and the implications to the morphological identification of the savannah species of the S. damnosum complex in West Africa are discussed. PMID- 1417209 TI - Phlebotomine sandfly species in Paraguay and their infection with Leishmania. AB - Nine species of sandflies, Lutzomyia (Nyssomyia) whitmani (Antunes and Countinho), Lutzomyia (Nyssomyia) intermedia (Lutz and Neiva), Lutzomyia (Psathyromyia) shannoni (Dyar), Lutzomyia migonei (Franca), Lutzomyia (Pintomyia) fischeri (Pinto), Lutzomyia (Pintomyia) pessoai (Countinho and Barretto), Lutzomyia cortelezzii (Brethes), Lutzomyia walkeri (Newstead) and Lutzomyia (Trichopygomyia) longispinus (Mangabeira), were caught, by human bait and Shannon trap, in four areas of Paraguay hyper-endemic for human leishmaniasis. Lutzomyia whitmani and L. intermedia were the predominant species. All the species collected were found to be anthropophilic. Hindgut infections with leishmanial promastigotes were observed in only one (0.38%) of the 266 L. whitmani dissected. No L. intermedia were found infected, giving an overall infection rate of one (0.16%) of 615 flies dissected. The results indicate a very low rate of natural infection in endemic areas of Paraguay. PMID- 1417210 TI - A study of the sugar chemoreception niches of two bulinid snail hosts of schistosomiasis. AB - Components of the sugar chemoreception niches of two host snails of urinary schistosomiasis, namely Bulinus globosus (Morelet) and Bulinus rohlfsi (Clessin), were measured by using a buccal mass olfactometer. Among the polysaccharides tested, amylose was found to be the strongest phagostimulant for adults and juveniles of both snail species. Other phagostimulants identified were maltose and xylose for B. rohlfsi and maltotriose for B. globosus. The a(1-4)-glucosidic linkage and the presence of glucose residues were found to be key factors in the stimulus recognition system of the snails. The possible use of these findings in the design of controlled-release formulations for the selective removal of schistosome host snails is considered. The ecological implications of these studies are also examined. PMID- 1417211 TI - The absence of Plasmodium falciparum gametocytes in the placental blood of a woman with a peripheral parasitaemia. PMID- 1417212 TI - The infective efficiency of intradermally inoculated Plasmodium coatneyi sporozoites. PMID- 1417213 TI - Sorbitol-induced aggregation of Plasmodium falciparum cultures. PMID- 1417214 TI - Does the snail Melanoides tuberculata have a role in biological control of Biomphalaria pfeifferi and other medically important African pulmonates? PMID- 1417215 TI - Placental Plasmodium falciparum parasitaemia in East Sepik (Papua New Guinea) women of different parity: the apparent absence of acute effects on mother and foetus. AB - The effects of malaria were studied in a group of parturient women of East Sepik Province, Papua New Guinea. Further information was gathered from a search of hospital records and interviews with village aid post orderlies. Examination of placental blood revealed a Plasmodium falciparum parasitaemia rate of 41% of the primiparae, 23% in parous 2, 25% in parous 3, and 3% in multiparae greater than 3. Approximately one-half of those with placental parasitaemia had a concomitant detectable peripheral parasitaemia. Placental parasitaemias were of relatively low density, averaging 1.6%. There were no instances in the observed series of births, hospital records, or village studies of the occurrence of severe malaria in the mother or its acute effects on the foetus. Neither birthweight nor maternal or cord blood haematocrit was related to the presence or absence of placental parasitaemia. Neonatal birthweight and risk of delivering a low birthweight (less than 2.5 kg) baby was statistically associated only with maternal parity. The possible reasons for the relatively benign effect of malaria in the pregnant women of this population are discussed. PMID- 1417216 TI - Cerebral blood flow and metabolism in hypothermic circulatory arrest. AB - Although hypothermic circulatory arrest has been accepted for use in cardiovascular operations, the potential for cerebral injury exists. The mechanism of the cerebral injury remains unclear. To address these questions we studied cerebral blood flow and metabolism. Sixteen puppies were randomly assigned to undergo either 45 or 90 minutes of hypothermic circulatory arrest after perfusion/surface cooling to 13 degrees C. Cerebral blood flow, cerebral oxygen and glucose metabolism, and cerebral vascular resistance measurements were obtained at 37 degrees C, 13 degrees C, 10 minutes after reperfusion, 30 degrees C and 2 and 4 hours after hypothermic circulatory arrest. No neurologic or behavioral changes were observed in any of the long-term survivors (11/16). Metabolic and cerebral blood flow data did not differ between groups. Cerebral blood flow was significantly lower in the late postarrest measurements, whereas oxygen and glucose consumption had returned to baseline values. In the presence of low cerebral blood flow and high cerebral vascular resistance it is notable that control levels of oxygen consumption were attained by abnormally high oxygen extraction. These data strongly suggest a vulnerable interval after hypothermic circulatory arrest in which cerebral metabolism is limited by cerebral blood flow. PMID- 1417217 TI - Does a posterior aneurysm increase the risk of endocardial resection? AB - The bias has been that the ideal anatomic circumstance for endocardial resection is the anterior left ventricular location. Posterior left ventricular aneurysms have been thought to be problematic to map and more difficult to close, and possibly to have a different substrate for ventricular tachycardia. To address this problem, we retrospectively reviewed the cases of 110 consecutive patients who underwent sequential endocardial resection for ventricular tachycardia between 1983 and 1991. Ninety-six patients had an anterior aneurysm, and 14 patients had a posterior aneurysm or infarct. Operative survival and 5-year survival were very similar between the two groups (p = not significant). A positive postoperative electrophysiological study was present in 11% of the anterior group versus 14% of the posterior group (p = not significant). There was a significantly greater incidence of mitral valve replacement in the posterior group, and we believe this was most likely due to frequent localization of the arrhythmia to the papillary muscle. Otherwise, patients with a posterior aneurysm or infarct had surgical results equivalent to those in patients with an anterior location. As long as there is a discrete aneurysm or infarct, endocardial resection is a safe and effective therapeutic procedure for ventricular tachycardia. PMID- 1417218 TI - Anomalous left coronary artery from the pulmonary artery: results of isolated aortic reimplantation. AB - Thirty-one consecutive children with anomalous left coronary artery underwent direct aortic reimplantation of the anomalous artery without an associated procedure. There were five deaths (16%; 70% confidence limits, 9% to 26%), three in the hospital and two early (within 3 months). The severity of preoperative left ventricular dysfunction was the only incremental risk factor for mortality: 31% mortality rate among patients with left ventricular shortening fraction of less than 0.20 versus 0% among patients with a left ventricular shortening fraction of 0.20 or more (p = 0.03). There were no late deaths up to 6 years, a survival rate of 84% +/- 7%. Late results were studied in 23 survivors having a follow-up of longer than 12 months. Ninety-six percent were free of symptoms; left ventricular function recovered to normal in all patients; moderate to severe mitral regurgitation decreased to minimal or no regurgitation in most patients (5/7); and the reimplanted anomalous left coronary artery was patent in each patient. Based on this study, we reached five conclusions. (1) Direct aortic reimplantation is technically feasible in most patients with anomalous left coronary artery and yields a high rate of late patency. (2) Left ventricular resection is unnecessary. (3) The mitral valve should not be interfered with at the initial operation, but mitral regurgitation may persist in a few patients and necessitate later operation. (4) In patients with moderate left ventricular dysfunction, the operative risk is low and early operation indicated. (5) In patients with severe left ventricular dysfunction, the operative risk is high; heart transplantation may be suggested, but our current approach favors an immediate corrective procedure. PMID- 1417219 TI - Anterior mediastinal tracheostomy with and without cervical exenteration. AB - Anterior mediastinal tracheostomy (AMT) facilitates resection of stomal recurrences after laryngectomy for carcinoma and tumors involving the cervicothoracic trachea and esophagus. Erosion of the innominate artery has been reported as a frequent major complication of AMT, and routine prophylactic division of the innominate artery with AMT has even been advised. Forty-four patients underwent AMT, 10 as an isolated procedure (for stomal recurrence [5], laryngeal carcinoma [1], or benign stenosis after laryngectomy [4]) and 34 with concomitant cervical exenteration (laryngopharyngoesophagectomy) for laryngeal, thyroid, or cervicothoracic esophageal malignancies. Transposition of the remaining tracheal stump beneath and to the right of the innominate artery to eliminate tension on the vessel was carried out in 14 patients (32%). Postoperatively, anastomotic leaks complicated nine of 31 pharyngogastric anastomoses. Iatrogenic hypoparathyroidism occurred in 10 patients. All six hospital deaths (14%) occurred in patients undergoing AMT with cervical exenteration, not isolated AMT. There was only one instance of innominate artery erosion. Survival was related to the pathology for which AMT was performed. Anterior mediastinal tracheostomy is a valuable adjunct in the treatment of select patients with malignancies of the cervicothoracic trachea and esophagus, and with attention to operative detail, innominate artery erosion should rarely, if ever, complicate the operation. Prophylactic division of the innominate artery with AMT is unnecessary. PMID- 1417220 TI - Postpneumonectomy syndrome: diagnosis, management, and results. AB - Airway obstruction may be caused by extreme mediastinal shift and rotation after right pneumonectomy or after left pneumonectomy in the presence of a right aortic arch. Eleven adults (aged 18 to 58 years) with severe symptoms were treated surgically between 5 months to 17 years after pneumonectomy (7 right, 4 left). An initial patient with only one functional lobe was treated unsuccessfully by aortic division and bypass graft. Ten underwent mediastinal repositioning. After two recurrences prostheses were used to maintain mediastinal position. Five patients who underwent such repositioning are doing well from 5 months to more than 5 years later. One died 1 month after operation probably of pulmonary embolism. One who showed residual airway collapse after operation has some recurrent obstruction. Three other patients who showed severe malacic obstruction of the airway after mediastinal repositioning variously underwent aortic division with bypass graft and tracheal and bronchial resection. One is well almost 6 years later. Two died postoperatively. Occurrence of the syndrome is unpredictable. Where malacic changes have not occurred, mediastinal repositioning may reasonably be expected to correct obstruction. Optimal treatment for concurrent severely malacic airways is unclear. PMID- 1417221 TI - Clinical and hemodynamic assessment of the Hancock II bioprosthesis. AB - The Hancock II bioprosthesis was used for heart valve replacement in 614 patients from 1982 to 1990. Aortic valve replacement (AVR) was performed in 376 patients, mitral valve replacement (MVR) in 195, and aortic and mitral valve replacement (DVR) in 43. The mean age was 62.7 years, and 78% of all patients were in New York Heart Association functional class III or IV before operation. Coronary artery bypass graft was necessary in 232 patients and replacement of ascending aorta in 55. There were 31 operative deaths (AVR, 4%; MVR, 6%; DVR, 9%). Follow up was complete in 98.5% of the patients and extended from 12 to 103 months, with a mean of 49 months. At the last follow-up, 85% of the patients were in New York Heart Association class I or II. The actuarial survival at 8 years was 79% +/- 3% for AVR, 68% +/- 4% for MVR, and 65% +/- 10% for DVR. The freedom from stroke at 8 years was 93% +/- 2% for AVR, 83% +/- 5% for MVR, and 90% +/- 5% for DVR. At the end of 8 years 96% +/- 1% of all patients were free from endocarditis, 92% +/ 1% were free from primary tissue failure, and 89% +/- 3% were free from reoperation. The actuarial freedom from valve-related death at 8 years was 98% +/ 1% for AVR, 86% +/- 5% for MVR, and 91% +/- 6% for DVR. Hemodynamic assessment was obtained by Doppler echocardiography in all operative survivors and demonstrated satisfactorily effective valve orifices and transvalvular gradients. The clinical results obtained with the Hancock II bioprosthesis have been gratifying, particularly in the aortic position. This bioprosthesis is our biological valve of choice. PMID- 1417223 TI - Predictive criteria for the need of extracorporeal circulation in single-lung transplantation. AB - Use of extracorporeal circulation is mandatory in heart-lung and en bloc double lung transplantation. However, no criteria exist to predict the necessity of its application during single-lung transplantation for parenchymal lung diseases. We therefore reviewed our experience in 23 patients undergoing single-lung transplantation for idiopathic pulmonary fibrosis. All patients were evaluated by preoperative right heart catheterization. For intraoperative monitoring, a pulmonary artery thermodilution catheter was placed in the contralateral lung to repeatedly assess pulmonary artery pressure, cardiac output, and pulmonary vascular resistance. Extracorporeal circulation was necessary during graft implantation in 4 patients, whereas 19 patients underwent operation without it. Preoperative demographic patient data, time of ischemia, and hemodynamic values obtained preoperatively and before the clamping of the pulmonary artery showed no significant differences between groups. In contrast, after the clamping of the pulmonary artery, a significant drop in cardiac index of about 1.5 L.min-1.m-2 (p less than 0.01) and a concomitant rise in pulmonary vascular resistance (p less than 0.01) was observed in the group requiring extracorporeal circulation, whereas these variables showed no significant changes in the other 19 patients. Pulmonary artery pressure rose significantly in both groups (p less than 0.05), without significant differences between them. It is concluded that intraoperative assessment of cardiac index and pulmonary vascular resistance is essential for estimation of cardiac performance during single-lung transplantation. A decrease in cardiac index of more than 1.5 L.min-1.m-2 after the clamping of the pulmonary artery rather than the degree of pulmonary hypertension is indicative of the need of extracorporeal circulation. PMID- 1417222 TI - Use of epicardial electrocardiograms for detecting cardiac allograft rejection. AB - Since the advent of cyclosporin A surface electrocardiograms have been unreliable for diagnosing cardiac allograft rejection. Although several noninvasive methods have been proposed, none have been sufficiently accurate to be considered for clinical use. We have studied the use of the QRS complex amplitude, the unipolar peak-to-peak amplitude, recorded from intramyocardial electrodes for detecting rejection. Ten adult mongrel dogs underwent placement of intramyocardial electrodes on each ventricle. After stabilization of signals the hearts were transplanted heterotopically into unmatched recipients receiving cyclosporin A, azathioprine and methylprednisolone. Endomyocardial biopsies were performed after stabilization of unipolar peak-to-peak amplitude, twice weekly thereafter, and when unipolar peak-to-peak amplitude fell significantly. This detected 13 of 14 episodes of rejection. There was one false-positive and one false-negative result. The false-negative study became positive the following day. Thus, analysis of unipolar peak-to-peak amplitude detected all episodes of rejection in a clinically relevant time frame and was able to detect mild forms of rejection and multiple episodes of rejection in the same heart even in the presence of therapeutic levels of cyclosporin A. PMID- 1417224 TI - Stentless porcine and pericardial valve in aortic position. AB - Fifty-seven patients underwent aortic valve replacement with a stentless glutaraldehyde-fixed bioprosthesis; 27 received a porcine aortic valve and 30 had a bovine pericardial valve. Two groups of 30 patients each who had aortic valve replacement with a tilting-disc mechanical valve or a stented porcine bioprosthesis served as controls. There were no differences in sex, body surface area, valve lesion, and valve size among the four groups. Results were assessed on a Doppler-based determination of maximum velocity across the valve, aortic valve area, and degree of valve regurgitation. Velocity across the valve was significantly less with stentless pericardial valves than with stentless porcine valves, stented bioprostheses, and mechanical valves. Stentless valves had a significantly larger aortic valve area when compared with stented valves. Mild central aortic insufficiency was detected more often with stentless pericardial than with stentless porcine bioprostheses (p = 0.04). Stentless valves showed a higher incidence of complete atrioventricular block when compared with stented valves (p = 0.04). Long-term studies are now warranted to assess the durability of both types of stentless valves. PMID- 1417225 TI - Transhiatal esophagectomy: a safe alternative for selected patients. AB - One hundred one consecutive patients underwent an esophagectomy with gastric interposition for benign and malignant processes from January 1982 through July 1990. Seventy-seven underwent transhiatal esophagectomy and 24, transthoracic esophagectomy. Multivariate analysis was performed comparing the hospitalization experience of the two groups. There was no significant difference found between the mean intraoperative blood loss for transhiatal esophagectomy (770 +/- 105 mL) and that of transthoracic esophagectomy (700 +/- 175 mL). There was a significant difference between operative time, with transhiatal esophagectomy averaging 5.4 hours and transthoracic esophagectomy averaging 7.3 hours. Postoperative stay was not significantly different although there was a wide range of values for the transthoracic esophagectomy group. An 8% operative mortality was experienced by both groups. There were a significant number of minor anastomotic leaks at the cervical anastomotic level for the transhiatal esophagectomy group, but all responded to nonoperative management. The highest morbidity and mortality were seen in the subgroup of transhiatal esophagectomies done for laryngocervical malignancies. The lowest morbidity and mortality were seen in the subgroup of 12 patients who underwent transhiatal esophagectomy for nonmalignant esophageal conditions. Transhiatal esophagectomy appears to be a safe alternative for early intrathoracic esophageal malignancies at any level, for bulky distal esophageal lesions, and for benign conditions requiring total esophagectomy. PMID- 1417226 TI - The learning curve for intraoperative echocardiography during congenital heart surgery. AB - Our group has previously reported a large prospective experience with the use of intraoperative echocardiography with Doppler color-flow imaging (IE-DCFI) during the repair of congenital heart defects. We have now performed IE-DCFI in 621 patients and have observed a major change in the impact of this technology, which has stabilized during our most recent experience (the last 207 patients). To evaluate the surgical learning curve with IE-DCFI, we divided patients into three groups: group 1, patients 1 through 207; group 2, patients 208 through 414; and group 3, patients 415 through 621. There were no major differences between groups with respect to age or disease entities. The average time needed to perform an IE DCFI examination decreased from 3.75 +/- 1.77 minutes in group 1 to 3.35 +/- 1.52 minutes in group 2 and has remained stable. The number of patients requiring revisions in the operating room (based on IE-DCFI findings) decreased from 17 (8%) in group 1 to 7 (3%) in group 2 to 5 (2%) in group 3. Furthermore, revisions were 100% successful in correcting the problem in groups 2 and 3, whereas 18% of group 1 patients left the operating room with persistent residual defects by IE DCFI. Surgeons can acquire the ability to interpret the results of IE-DCFI themselves and use it to enhance their operative repair of congenital heart defects, but this requires an experience of at least 200 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417227 TI - Emergent applications of cardiopulmonary support: a multiinstitutional experience. AB - The use of emergent portable bypass systems is increasing. Because of limited patient use in any one institution, a combined experience can better determine the applicability of these systems. A total of 187 patients from 17 centers were analyzed. Causes leading to bypass initiation were cardiac arrest (125 patients), cardiogenic shock (44), profound hypothermia (7), pulmonary insufficiency (9), and miscellaneous (2). Weaning from bypass was successful in 30.5% (57 patients). Sixty-four patients (34.2%) were transferred to standard bypass or other modes of circulatory assist. Of the total population, 40 patients (21.4%) were alive greater than 30 days. There were no survivors of unwitnessed arrests. Major diagnostic or therapeutic interventions were carried out on bypass in 74.9% of all patients. In survivors, 77.1% (37/48) had major therapeutic interventions as compared with 50.0% (67/135) of nonsurvivors. Emergency portable bypass systems can successfully resuscitate and support cardiac hemodynamics, although the underlying causes necessitating bypass remain difficult to correct. When corrective intervention can be performed, there is an increased chance of survival. Unwitnessed arrest, prolonged cardiopulmonary resuscitation, and lack of treatment options are relative contraindications. Appropriate patient selection and early application of these systems should lead to improved survival. PMID- 1417228 TI - Effect of light dose on the photodynamic destruction of endobronchial tumors. AB - The effects of various light power densities (milliwatts per centimeter of diffusing fiber [mW/cf]) and light doses (joules per centimeter of diffusing fiber [J/cf]) on the effectiveness of photodynamic therapy to endobronchial and tracheal tumors were evaluated at 46 different sites. All patients had squamous cell carcinoma or adenocarcinoma. They received 2 mg/kg body weight dihematoporphyrin ether intravenously 2 days before treatment bronchoscopy. Only one light treatment was delivered to the site. Patients were treated with diffusing cylinder light tips and underwent toilet bronchoscopy 2 days after photodynamic therapy. The percentage of obstruction was estimated before and after treatment and before and after toilet bronchoscopy. There was no difference between the effects resulting from power densities of 400 and 500 mW/cf, nor were there differences in the reactions between squamous cell carcinoma and adenocarcinoma. The amount of tumor that could be removed at the end of the treatment bronchoscopy, the amount of reobstruction by secretions and exudate seen at toilet bronchoscopy, and the final percent decrease in obstruction at the end of toilet bronchoscopy were proportional to the light dose. Because the final percentage decrease in obstruction plateaued at light doses of 400 to 500 J/cf and there was no statistically significant difference between 400 and 500 J/cf, we recommend using a power density of 500 mW/cf and a light dose of 400 J/cf during photodynamic therapy. PMID- 1417229 TI - Nicardipine: myocardial protection in isolated working hearts. AB - The effectiveness of the calcium antagonist nicardipine in protecting the ischemic myocardium was evaluated using the hemodynamic recovery of isolated working rat hearts subjected to hyperkalemic cardiac arrest followed by ischemia at 37.5 degrees C and 10 degrees C. Rat hearts (n = 51) received 20 mL of cardioplegia and were subjected to 27 minutes of ischemia at 37.5 degrees C. Group A (control) did not receive nicardipine. Groups B through F received nicardipine in the cardioplegia with total doses ranging from 2 micrograms to 6 micrograms. Group A had 46% survival of ischemia, whereas groups C (3 micrograms) and D (4 micrograms) had survival rates of 88% and 100%, respectively (p less than 0.05). The recovery of aortic flow after ischemia was 35% in group A, compared with 76% in group B (2 micrograms) and 81% in group D (p less than 0.05). Group A had 49% postischemic recovery of cardiac output, whereas groups B and D had 82% and 85% recovery (p less than 0.05). The postischemic recovery of stroke volume was 48% in group A compared with 84% in group B, 87% in group D, and 73% in group E (5 micrograms) (p less than 0.05). Additional rats were exposed to 210 minutes of ischemia (n = 41) or 240 minutes of ischemia (n = 56) at 10 degrees C. Control groups did not receive nicardipine, whereas treatment groups received nicardipine in the cardioplegia with total doses ranging from 1.4 micrograms to 6.4 micrograms. There were no significant differences in the survival of ischemia or the recovery of function after ischemia at 10 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417230 TI - Electrophysiologic study of dysrhythmias after atrial operations in dogs. AB - Experiments were conducted with 159 dogs to investigate the mechanism of persistent dysrhythmias clinically encountered after atrial-level operations. Those found after incisions to the internodal pathways (INPs) of the right atrium were analyzed using cardiac mapping in an anesthetized or extracorporeally perfused state. Longitudinal incisions of the posterior INP often allowed inducible sustained atrial flutter, with circus movement of excitation around the right atrium near the tricuspid orfice. Sustained atrial flutter thus produced was modified in cycle length by coexisting division of the middle INP but inhibited by that of the anterior INP. Its incidence increased at chronic stage, with marked cicatricial changes. The disrupted anterior INP markedly prolonged conduction time to the atrioventricular node and A-H interval compared with the other disruptions. Persistent atrioventricular junctional rhythm developed in about 50% of the animals after disruption of all three INPs or anterior and posterior INPs; division of the anterior INP was the common potent factor, although no single blocked INP produced persistent junctional rhythm. Our results support the "summation theory." The incidence of junctional rhythm and hypoxia of the sinoatrial node (flow rate of less than 10 mL.100 g-1.min-1) were markedly enhanced by coexisting blockade of atrial feeding arteries in addition to division of the anterior INP. In conclusion, massive posterior INP disruption is a potent anatomic substrate in producing sustained atrial flutter, middle INP division a modifier, and anterior INP division an inhibitor. Division of the anterior INP is a potent anatomic substrate in producing junctional rhythm, and hypoxia involving the sinoatrial node reacts as its synergic factor. PMID- 1417231 TI - Time for new concepts about measurement of complement activation by cardiopulmonary bypass? AB - Fifty-one patients admitted for routine coronary bypass operations were randomized to cardiopulmonary bypass with a membrane oxygenator (Capiox) or a bubbler (Polystan or William Harvey). Complement activation was measured using enzyme immunoassays for concentrations of C3 activation products and the terminal complement complex. From 5.8 to 8.1 arbitrary units (AU)/mL (medians), the plasma concentrations of C3 activation products increased by 119.9 AU/mL (Capiox), 124.6 AU/mL (Polystan), and 79.5 AU/mL (William Harvey) to a peak at closure of the sternum (not significant when related to baseline concentrations). The increase in C3 activation products and baseline C3 activation were linearly correlated (R2 = 0.30; p less than 0.0001). From 5.5 to 6.1 AU/mL, the plasma terminal complement complex concentrations increased by 45.2 AU/mL (Capiox), 15.4 AU/mL (Polystan), and 17.4 AU/mL (William Harvey) to a peak before termination of cardiopulmonary bypass. Maximal terminal (C5-C9) activation was significantly higher in the membrane oxygenator group (p less than 0.0001) and showed no relationship to C3 activation. Measurement of C3 activation only gives no information about C5-C9 activation. At present, terminal complement complex quantitation is probably the best index of C5-C9 activation during cardiopulmonary bypass. PMID- 1417232 TI - Congenital malformations of the coronary arteries: the Texas Heart Institute experience. AB - Coronary artery anomalies, some of which are considered clinically insignificant, can be associated with other congenital heart defects, myocardial ischemia, and reduced life expectancy. We conducted a retrospective study to determine the efficacy of surgical treatment in 191 patients who had a total of 202 coronary artery anomalies, which were classified as anomalies of origin (88 patients), termination (93), or distribution (10). Of the 88 patients with anomalies of origin, 60 had a coronary artery arising from the pulmonary artery, 18 had a right coronary artery arising from the left anterior descending artery, and 10 had a coronary artery arising from the contralateral sinus of Valsalva. All patients with an anomaly of termination had a coronary arteriovenous fistula, and all patients with an anomaly of origin had a single coronary artery. The diagnostic and operative techniques for each of the defects are evaluated. Based on our experience, early diagnosis and surgical intervention can yield satisfactory results in patients with coronary artery anomalies, with most experiencing relief of symptoms. The operative procedures were associated with a low early and late mortality; in addition, few patients experienced complications. PMID- 1417233 TI - Endotoxin release and tumor necrosis factor formation during cardiopulmonary bypass. AB - Endotoxin, when released into the systemic circulation during cardiopulmonary bypass (CPB), might induce activation of plasmatic systems and blood cells during CPB, in addition to a material-dependent blood activation during CPB. However, the role of endotoxin in the development of this so-called whole-body inflammatory reaction in CPB is still unclear. We investigated the release of endotoxin into the systemic circulation in relation with the activation of the complement system and in particular the formation of tumor necrosis factor in 10 patients undergoing CPB. Immediately after the start of CPB the endotoxin concentrations increased significantly (p less than 0.01), accompanied by increases in C3a concentration (p less than 0.05). After release of the aortic cross-clamp, there was a second increase in endotoxin followed by a continuous increase in tumor necrosis factor, reaching a peak concentration 1 hour after the end of CPB (p less than 0.01). These observations demonstrate a release of endotoxin into the systemic circulation associated with tumor necrosis factor formation, which contributes to the whole-body inflammatory reaction associated with CPB. PMID- 1417234 TI - Temperature monitoring during CPB in infants: does it predict efficient brain cooling? AB - We examined jugular venous oxygen saturation data in 17 pediatric patients less than 1 year of age undergoing hypothermic cardiopulmonary bypass (CPB). Jugular venous oxygen saturations (JvO2SATS) were measured before bypass and during the active core cooling portion of CPB. The study intervals during CPB included 1 minute after initiation of CPB, at a tympanic membrane temperature of 15 degrees C, and at a rectal temperature of 15 degrees C. During these measurement intervals, there were no significant changes in mean arterial pressure, pump flow rate, arterial oxygen saturation, mixed venous oxygen saturation, carbon dioxide tension, or hematocrit. Six of the 17 patients (29%) demonstrated a significantly lower JvO2SAT (87.1% +/- 6.3% versus 98.1% +/- 0.9%) at a tympanic membrane temperature of 15 degrees C. Patients demonstrating jugular venous desaturation could not be predicted from continuous monitoring of tympanic membrane and rectal temperatures or through on-line measurements of mixed venous oxygen saturation. Low JvO2SAT suggests higher levels of cerebral metabolism and cerebral uptake of oxygen. In the presence of deep hypothermic CPB and stable anesthetic levels, the most likely cause of a low JvO2SAT is inadequate cerebral cooling. We believe JvO2SAT monitoring may be an important adjunct to conventional temperature monitoring in the patient undergoing deep hypothermic CPB or total circulatory arrest. PMID- 1417235 TI - Surgical management of infective endocarditis in children. AB - Infective endocarditis occurs infrequently in the general pediatric population, occurring mostly in patients with congenital heart disease. This study reviews our surgical experience with infective endocarditis based on a policy of aggressive intervention, conservative operative debridement, and creative reconstruction options using pericardium and prosthetic heart valves. From 1982 to 1989, 16 patients, 3 weeks to 16 years of age, underwent 19 intracardiac operations for infective endocarditis therapy at Kosair Children's Hospital. Eight (42%) were for resection of vegetations alone; an additional 11 operations (58%) involved more extensive debridements requiring either valve replacement or valvuloplasty using pericardium for exclusion of an abscess cavity, closure of a fistula, or for valve repair. Operative mortality was 25% (4 patients) and related to preoperative disease severity. There was one late death. Offending organisms included Staphylococcus species (31%), Haemophilus influenzae (13%), pneumococcus (5%), gram-negative organisms (13%), and Candida (13%); no organism grew on culture in 25%. We conclude that aggressive surgical exploration in patients with infective endocarditis is indicated and often requires resection of vegetations alone. More extensive procedures should preserve as much valvular tissue as possible. Pericardium is useful for reconstruction after debridement. PMID- 1417236 TI - Left ventricular diverticulum with hypertrophy of the left ventricular apex. AB - A surgical case of diverticulum in the left ventricular apex is presented. A two dimensional echocardiogram and magnetic resonance image showed a calcified tumor buried in the marked hypertrophied apex of the left ventricle. Enucleation of the oval and hard tumor (4 x 2.5 x 2.5 cm) was performed through the apex, and the defect was anastomosed by buttress sutures. Histologic examination demonstrated that the tumor cavity was filled with a thrombus encapsulated by thickened and calcified endocardium that extended to the left ventricular cavity. In this report, the etiology of the diverticulum with a hypertrophied myocardium is discussed. PMID- 1417237 TI - Chronic fibrosing mediastinitis and superior vena caval obstruction from blastomycosis. AB - Chronic fibrosing mediastinitis is most commonly a complication of granulomatous disease caused by histoplasmosis. We report a case of Blastomyces dermatitidis causing superior vena caval obstruction from fibrosing mediastinitis. PMID- 1417238 TI - Saphenous vein graft pseudoaneurysm formation after postoperative mediastinitis. AB - Pseudoaneurysm formation involving the body of an aortocoronary saphenous vein graft is a rare event. True aneurysmal dilatation of the graft and anastomotic pseudoaneurysm formation occur more commonly. We present the case of a 73-year old woman in whom a pseudoaneurysm communicating with the body of a posterior descending coronary artery saphenous vein graft developed, presumably after a postoperative sternal wound infection. The aneurysm was excised and the defect within the saphenous vein graft repaired using hypothermia and circulatory arrest. PMID- 1417239 TI - Unusual complication of temporary pacing wires in children. AB - There have been numerous complications described concerning temporary epicardial pacing wires including infection, bleeding, and coronary artery graft disruption. We report a case in which the heart was ensnared by the pacing wire, resulting in cardiac decompensation during attempted removal. This complication may be avoided by assuring that a smaller loop of pacing wire remains in the pericardium. PMID- 1417240 TI - Aneurysm of coronary arteriovenous fistula presenting as a calcified mediastinal mass. AB - A 61-year-old woman with a giant aneurysm of the coronary arterial fistula between the left anterior descending coronary artery and the main pulmonary artery underwent aneurysmal resection and closure of the fistula. This was a very unusual case with rare congenital malformation with secondary atherosclerotic change. PMID- 1417241 TI - Bilateral elastofibroma dorsi. AB - Elastofibroma dorsi was diagnosed in a 76-year-old woman with bilateral subscapular tumor masses and a 3-year history of recurrent, right-sided scapular pain. A bilateral tumor extirpation was performed and the patient left the hospital free of symptoms 10 days later. We suggest that both constant trauma with resulting excessive elastin production and collagen degeneration might play a major role in the pathogenesis of this rare proliferative lesion. PMID- 1417242 TI - Double-lung transplantation using donor lungs with a right tracheal bronchus. AB - A 58-year-old man underwent sequential bilateral lung transplantation. On the donor heart-lung block, it was discovered that the right apical segment was supplied by a tracheal bronchus. After the separate implantation of both lungs, a right apical segmentectomy was performed and the postoperative course was uneventful. The management of this problem is discussed. PMID- 1417243 TI - Surgical management of left coronary artery ostial atresia and supravalvar aortic stenosis. AB - Congenital atresia of the left main coronary artery ostium is a rare lesion, particularly when found in association with supravalvar aortic stenosis. This report describes the preoperative evaluation and surgical management of this lesion found in conjunction with a quadricuspid aortic valve in a 5-year-old child. Patch aortoplasty and left internal thoracic artery to left anterior descending coronary artery bypass were performed to correct this lesion. PMID- 1417245 TI - Pericardial repair of a tracheal laceration during transhiatal esophagectomy. AB - Transhiatal esophagectomy has recently been popularized for both benign and malignant esophageal disease. While we were performing a transhiatal esophagectomy for a squamous cell cancer of the upper third of the esophagus, a tear in the membranous trachea near the carina occurred. This was repaired through the cervical incision with a free pericardial patch. This solution to a potentially catastrophic complication of transhiatal esophagectomy gave a satisfactory result without early or late postoperative respiratory complications. PMID- 1417244 TI - Hyperbaric oxygen: value in management of nonhealing saphenectomy wounds. AB - The greater saphenous vein is commonly used as a conduit for arterial bypass in both cardiac and peripheral vascular operations. Although saphenectomy wound complications occur infrequently, such problems may be quite serious. We report a case in which hyperbaric oxygen therapy was extremely valuable in the management of a very difficult saphenectomy wound. PMID- 1417246 TI - Limited vertical skin incision for median sternotomy. AB - The cosmetic deformity of the vertical skin incision for median sternotomy was decreased by using a mechanical traction system to increase exposure at the superior margin of a shorter wound. The limited vertical skin incision did not impede technical surgical maneuvers and produced a scar that was more acceptable than submammary incision or right anterior thoracotomy. The limited skin incision is especially useful in young women with congenital heart disease. PMID- 1417248 TI - Bilateral anterior thoracotomy for automatic implantable cardioverter defibrillator placement in patients with previous sternotomy. AB - Bilateral anterior thoracotomy, extrapericardial patches, and endocardial sensing lead placement have been used in 40 patients with previous sternotomy. The mean defibrillation threshold was 15 J, and in all patients the defibrillation threshold was less than 20 J. The surgical procedure is simplified with less risk by avoiding dissection of previously operated regions. Serious pulmonary complications have been avoided by adequate pain control with epidural analgesia and early mobilization. This technique has successfully been used in patients with underlying chronic obstructive pulmonary disease and amiodarone-induced pulmonary fibrosis. All patients have been extubated by the first postoperative day. PMID- 1417247 TI - Directed atraumatic coronary sinus cannulation for retrograde cardioplegia administration. AB - A simple method of coronary sinus cannulation for retrograde cardioplegia administration is described that reduces cardiac manipulation. Intraoperative transesophageal echocardiography is used to direct atraumatic coronary sinus cannulation, confirm the depth of insertion of the cannula tip in relation to the ostium, and reduce overall cannulation time. PMID- 1417249 TI - New side-holed sheath for intraaortic balloon pumping to maintain limb perfusion. AB - We developed a new side-holed shunt sheath for inserting intraaortic balloon pumps to maintain lower limb perfusion in patients with stenotic and tortuous aortoiliac arteries. This sheath has a large internal diameter and several side holes, which act as an internal shunt. It was useful and effective in 11 patients with severe aortoiliac occlusive lesions who required assistance by intraaortic balloon pumping. PMID- 1417250 TI - New surgical technique for type B aortic interruption. AB - Restoring continuity of the aortic arch in aortic interruption continues to be a problem in terms of both surgical technique and long-term results. We report here a surgical technique using the left subclavian artery along with an aberrant right subclavian artery to form a conduit in a patient with type B interruption, to reestablish aortic continuity. PMID- 1417251 TI - Video-assisted thoracic surgery: basic technical concepts and intercostal approach strategies. AB - Video-assisted thoracic surgery is emerging as a viable approach to a number of intrathoracic disorders. Technical difficulties related to improper instrument selection and suboptimal intercostal operative access can reduce the utility of, and the enthusiasm for, the video-assisted thoracic surgical approach. This report describes the intercostal access strategy and the instrument positioning that we now prescribe for many video-assisted thoracic surgical procedures. These approaches have become refined during the course of our experience with 467 patients undergoing video-assisted thoracic operations over the last 18 months. PMID- 1417252 TI - Esophageal perforation. PMID- 1417253 TI - Ross' first homograft replacement of the aortic valve. PMID- 1417254 TI - Continuous normothermic blood cardioplegia: simplified delivery circuit. PMID- 1417255 TI - Thromboelastogram and postoperative hemorrhage. PMID- 1417256 TI - Thromboelastogram and postoperative hemorrhage. PMID- 1417257 TI - Thromboelastogram and postoperative hemorrhage. PMID- 1417258 TI - The blue man phenomenon. PMID- 1417259 TI - Minimal hemodilution and optimal potassium use during normothermic aerobic arrest. PMID- 1417260 TI - Rapid transfusion after aortic decannulation. PMID- 1417261 TI - Aortic valve repair. PMID- 1417262 TI - 1985: A method for predicting postoperative lung function and its relation to postoperative complications in patients with lung cancer. 1992 update. PMID- 1417263 TI - Thermo cardiosystems left ventricular assist device. PMID- 1417264 TI - Plateletpheresis and transfusion practice in heart operations. PMID- 1417265 TI - Preoperative morphologic and physiologic assessment of internal thoracic arteries. PMID- 1417266 TI - Manual versus stapled bronchial closure: still controversial. PMID- 1417267 TI - Hemodynamic effects of pericardial closure. PMID- 1417268 TI - Abrupt cardiac failure using a right VAD in the presence of a tricuspid valve prosthesis. PMID- 1417269 TI - Allogenic vein as a conduit for coronary artery bypass. PMID- 1417270 TI - Intrathecal perfusion of an oxygenated perfluorocarbon prevents paraplegia after aortic occlusion. AB - A canine model was used to evaluate the effects of continuous intrathecal perfusion of an oxygenated perfluorocarbon emulsion on systemic and cerebral hemodynamics and neurologic outcome after 70 minutes of normothermic aortic occlusion. Twelve mongrel dogs were instrumented to monitor proximal and distal arterial blood pressure, cerebrospinal fluid pressure, spinal cord perfusion pressure, and somatosensory evoked potentials. The intrathecal perfusion apparatus consisted of two perfusing catheters, placed in the intrathecal space through a laminectomy, and a draining catheter percutaneously inserted in the cisterna cerebellomedullaris. The aorta was cross-clamped just distal to the left subclavian artery for 70 minutes. Animals were randomized into two groups: group 1 (n = 6) animals were treated with intrathecal perfusion of saline solution, whereas group 2 (n = 6) animals received oxygenated Fluosol-DA 20%. Data were acquired at baseline, during the cross-clamp period, and after reperfusion. Normothermic Fluosol or saline solution was infused at a rate of 15 mL/min beginning 15 minutes before cross-clamping and continued throughout the ischemic interval. There was no difference in proximal arterial blood pressure (97.2 versus 95.4 mm Hg; p > 0.05) or distal arterial blood pressure (14.6 versus 15.0; p > 0.05) between the two groups throughout the cross-clamp interval. Cerebrospinal fluid pressure rose significantly in both groups with the onset of intrathecal perfusion of either saline solution or Fluosol (7 +/- 1 versus 24 +/- 5 and 8 +/- 1 versus 40 +/- 4 mm Hg, respectively; p < 0.05). The rise in cerebrospinal fluid pressure was sustained throughout the perfusion interval in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417271 TI - Cryopreserved allograft veins as alternative coronary artery bypass conduits: early phase results. AB - Traditional autologous conduits are sometimes unavailable or unsuitable to permit total revascularization during coronary artery bypass grafting. In these patients the results of using nonautologous alternative conduits has been disappointing. Encouraged by the excellent long-term results seen with cryopreserved allograft valves, a clinical protocol was developed to evaluate the use of a commercially cryopreserved allograft saphenous vein (CPV). Our protocol consisted of using CPV when left internal mammary arteries and autologous saphenous vein grafts were unavailable or unsuitable for complete revascularization. Blood group (ABO) typed CPVs were thawed and implanted as required using standard surgical techniques. From December 1989 through June 1991, 19 of 1,602 patients who underwent coronary revascularization had CPVs implanted (1.2%). There were no operative deaths. An attempt was made to evaluate the patency of all grafts with coronary arteriography or ultrafast computed tomographic scans. Fourteen patients were available for patency evaluation. Patency rate in the 14 patients studied at a mean of 7 +/- 2 months (range, 2 to 16 months) were: internal mammary artery, 93% (14/15); saphenous vein graft, 80% (4/5); and CPV, 41% (7/17). The patency of the CPV was significantly less than the patency rate for the saphenous vein and internal mammary artery (p = 0.004). We conclude that the short-term patency rate of CPVs is inferior to that of autologous vessels. Due to its poor patency, we recommend that CPV should only be used when no other autologous conduit is available. PMID- 1417272 TI - Late results of operation for ventricular tachycardia. AB - We have analyzed results in 54 consecutive patients with recurrent ventricular tachycardia and coronary artery disease in whom we used an aggressive surgical approach involving map-directed ventricular tachycardia ablation, scar excision and left ventricular remodeling, and coronary artery bypass grafting, as well as staged mitral valve replacement when necessary. We have previously shown age greater than 65 years to be an independent predictor of mortality and have excluded such patients from this series. Average age was 56 +/- 7 years. All patients had a previous myocardial infarction; 24% of the infarctions (13/54) were posterior in location. Symptoms included syncope or presyncope in 83% of the patients (45/54), angina in 54% (29/54), and congestive heart failure in 52% (28/54). Extensive coronary artery disease was found in 78% (42/54), and 89% (48/54) had serious compromise of left ventricular function (ejection fraction < 0.40; average ejection fraction, 0.28 +/- 0.12). Only 63% (34/54) appeared to have a resectable left ventricular aneurysm on the preoperative angiogram. Ablation techniques included endocardial excision in 82% (44/54), with the addition of cryoablation in 60% (32/54), and balloon electric shock ablation in 22% (12/54); coronary artery bypass grafting was performed in 85% (46/54). There were four hospital deaths (7%). The surgical cure rate (no inducible VT at postoperative electrophysiologic study was 72% (39/54). During follow-up (mean, 50 +/- 31 months) there have been six late deaths (1 sudden death, 1 stroke, 4 congestive heart failures with or without mitral regurgitation). Four patients with progressive congestive heart failure and serious mitral regurgitation have undergone repeat operation for mitral valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417273 TI - Cardiac retransplantation: a viable option? The Registry of the International Society for Heart and Lung Transplantation. AB - To evaluate cardiac retransplantation as an appropriate utilization of scarce donor organs we analyzed data from the registry of the International Society for Heart and Lung Transplantation (ISHLT) (n = 449) and the Utah Cardiac Transplant Program (n = 20). Actuarial survival among retransplants was lower than in patients who received only one transplant in both the ISHLT registry patients (1 year survival, 48% versus 78%; p = 0.001) and the Utah series (1 year survival, 74% versus 88%; p = 0.06). Uncontrolled rejection, short interval (< 6 months) between transplantations, and the need for mechanical circulatory support were identified as risk factors for retransplantation. The incidence of rejection and infection was similar in first and second transplant recipients. Second transplant recipients had a higher level of sensitization, a greater incidence of donor-specific positive crossmatches, and an increased early mortality. Repetition in the second donor of mismatched HLA antigens present in the first donor did not adversely affect survival. If patients who underwent retransplantation within 6 months of their initial transplantation, those receiving transplants for uncontrolled rejection, and those requiring mechanical assistance were eliminated from the study, the short-term and long-term survival after cardiac retransplantation does not differ from that in patients having a single transplant. PMID- 1417274 TI - Acute rejection of lung allografts with various immunosuppressive protocols. AB - Between February 1990 and December 1991, 69 patients who survived for a minimum of 5 days after single-lung (27), double-lung (32), or heart-lung transplantation (10) were studied to learn the incidence and severity of acute rejection and the possible effects of various immunosuppressive protocols on this rejection. Acute rejection was less common (2.1 versus 3.1 episodes/patient) after transplantation in those 30 candidates who received rabbit antithymocyte globulin for the first 5 postoperative days versus the 28 who were maintained on cyclosporine, azathioprine, and prednisone alone (p < 0.05), but no patient escaped at least one episode. Patients given cyclosporine received more 3-day courses of methylprednisolone (p < 0.02) than those given rabbit antithymocyte globulin (2.5 versus 1.7 courses). Although no disadvantage in terms of infectious morbidity was noted in the rabbit antithymocyte globulin group, no obvious intermediate advantage was noted in survival (85% at 12 months) or grade of rejection or airway flows. The most common histopathologic grades were mild (A2) and moderate (A3); the average grade was A2.3. FK 506 was tested in 11 patients, and early results are promising relative to low early and likely fewer late episodes of rejection. No differences were noted in the likelihood of rejection for any procedures. PMID- 1417275 TI - Improved myocardial ischemic tolerance by contractile inhibition with 2,3 butanedione monoxime. AB - Contracture of the arrested myocardium during prolonged storage of the heart results in both systolic and diastolic dysfunction, and is a major limitation to extended preservation. We studied the effects of a reversible contractile inhibitor, 2,3-butanedione monoxime (BDM), on myocardial ischemic tolerance. Isolated rabbit hearts were flushed with University of Wisconsin (UW) solution with and without 30 mmol/L BDM and 1 mmol/L CaCl, stored at 4 degrees C for 24 hours, and subsequently reperfused for 60 minutes. Left ventricular pressure volume relationships and adenine nucleotide content were determined before reperfusion. Left ventricular systolic pressure, diastolic volume, and adenine nucleotide content were measured after reperfusion. Hearts stored in UW solution underwent contracture and adenosine triphosphate (ATP) depletion during storage, and exhibited systolic dysfunction, impaired diastolic relaxation, and poor ATP regeneration upon reperfusion. The addition of calcium worsened contracture and ATP depletion (p < 0.005) and slightly improved function and ATP regeneration (p = not significant). Hearts stored in the presence of BDM experience no contracture during storage; ATP was preserved (10.7 versus 15.7 nmol/mg; p < 0.05), and left ventricular systolic pressure and ATP content recovered to 74% and 93% of control on reperfusion, respectively (p < 0.005). Left ventricular diastolic volume remained depressed, however, although less than with UW solution (0.87 versus 0.45 mL; p < 0.001). When both BDM and calcium were included in the UW solution, calcium-stimulated ATP hydrolysis and contracture were prevented, left ventricular systolic pressure returned to 87% of control, and left ventricular diastolic volume and ATP content returned to control levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417276 TI - Extracorporeal membrane oxygenation for cardiac failure after congenital heart operation. AB - Despite continuing improvement in myocardial protection and surgical technique, the repair of complex congenital heart lesions can result in cardiopulmonary compromise refractory to conventional therapy. In a 29-month period, 24 patients (aged 14 hours to 6 years) were treated with extracorporeal membrane oxygenation (ECMO) 28 times for profound cardiopulmonary failure. Four patients required ECMO after each of two cardiopulmonary bypass procedures. Seventeen patients required ECMO to be initiated in the operating room: 12 (71%) were weaned successfully from ECMO, and 8 (47%) survived. Seven patients had ECMO initiated in the intensive care unit: 6 (86%) were weaned, and 5 (71%) survived. Serial echocardiograms demonstrated substantial recovery of cardiac function in 18 of 21 instances (86%) of ventricular failure from myocardial dysfunction. Overall, 18 of 24 patients (75%) were successfully weaned from ECMO including all 4 who underwent 2 ECMO treatments. We conclude that ECMO can successfully salvage children who have serious cardiopulmonary failure immediately after a congenital heart operation and that long-term survival is possible after two ECMO treatments. PMID- 1417277 TI - Coarctation of the aorta in infants: does the aortic arch grow after repair? AB - Infants with coarctation of the aorta frequently require a corrective operation during the first year of life. These patients frequently have a smaller than normal transverse aortic arch. Despite good repairs with different techniques, the proximal transverse aortic arch often remains smaller than normal. The hemodynamic molding theory predicts that growth of the aortic arch should occur when normal flow is established through the aortic arch. Preoperative and postoperative aortograms were reviewed in patients who underwent subclavian flap aortoplasty for the repair of coarctation. Patients were divided into two groups. Subclavian flap aortoplasty was performed at 1 month of age or earlier in group I, and at more than 1 month but less than 1 year of age in group II. Aortograms performed in patients without coarctation were used as age-matched controls (group III). The transverse aortic arch in groups I and II did grow and were compared with the control group. Group I patients achieved more growth than those in group II. No aortic arch gradients were present at postoperative follow-up. PMID- 1417278 TI - Postinfarct ventricular septal defect repair: effect of coronary artery bypass grafting. AB - Between June 1968 and April 1991, 75 patients who had undergone coronary angiography underwent repair of a postinfarction ventricular septal defect. Group 1 (n = 33) includes patients who had two- or three-vessel serious (> 75% narrowing) proximal coronary artery disease and underwent complete revascularization in addition to repair of the ventricular septal defect. Group 2 (n = 19) patients also had two- or three-vessel coronary artery disease but bypass grafting was not performed; only the ventricular defect was repaired. Group 3 (n = 23) patients had only single-vessel coronary artery disease that corresponded to the region of the infarct; they underwent ventricular septal defect repair only. Follow-up of hospital survivors was 96% complete at a mean of 86.2 months (range, 1 to 288 months). Hospital mortality after ventricular septal defect repair was 21.2% in the cohort with bypassed coronary artery disease (group 1), 26.3% in those with unbypassed disease (group 2), and 26.1% in those with only single-vessel coronary artery disease (group 3) (p = 0.88). With follow up after 5 and 10 years, the actuarial survival was 72.2% +/- 8% and 47.8% +/- 10%, respectively, in the bypassed group, 29.2% +/- 11% and 0%, respectively, in the unbypassed group, and 52.2% +/- 10% and 36.5% +/- 11%, respectively, in the cohort with single-vessel disease. Bypassing associated coronary artery disease significantly increased long-term survival when compared with patients with unbypassed coronary artery disease (p = 0.0015). PMID- 1417279 TI - Risk analysis of operative intervention for failed coronary angioplasty. AB - To assess the outcome of emergency coronary artery bypass grafting (CABG) after failed percutaneous transluminal coronary angioplasty (PTCA), 91 patients undergoing emergency CABG after failed PTCA over a 30-month period ending July 31, 1991, were studied. For reference, a cohort of patients (91) concurrently undergoing elective CABG equally matched for age, sex, number of grafts, ventricular function, and reoperative status was compared. Specific outcomes including death, hospital length of stay, use of blood products, and development of myocardial infarction were analyzed. More than half the patients undergoing emergency CABG for failed PTCA required three or more grafts. Operative mortality was 12.1% (11/99) for emergency CABG compared with 1% (1/91) for elective case matched CABG patients (p = 0.007). Emergency CABG patients required frequent use of postoperative inotropes (p = 0.02) and intraaortic balloon counterpulsation (p = 0.001). Length of hospital stay (p = 0.005), administration of blood products (p = 0.009), postoperative myocardial infarction (p = 0.0005), and ventricular arrhythmias (p = 0.0004) were increased after emergency compared with elective CABG. The presence of multivessel disease or use of a reperfusion catheter had no influence on clinical outcome. Despite accumulated experience and improved operative management, patients requiring emergency CABG for failed PTCA remain at increased risk for postoperative complications and death. PMID- 1417280 TI - Partial median sternotomy for repair of heart defects: a cosmetic approach. AB - A modified median sternotomy incision that results in a cosmetically appealing scar is described. It includes the use of a low-lying short skin incision and partial transection of the sternum. The outcome in 182 infants and children indicates that this approach is safe, provides adequate exposure, and has excellent cosmetic results. PMID- 1417281 TI - Surgical considerations in bypassing coronary arteries with 100% proximal occlusion. AB - Objective data on the ability of cineangiography to predict the size of reconstituted totally occluded coronary arteries, as well as the clinical outcome of such revascularization, are sparse. Accordingly, we reviewed 200 consecutive cases of coronary revascularization to determine the answers to these questions. Group I patients (n = 57, with 86 totally occluded coronary arteries) had at least one coronary artery with a 100% proximal occlusion that reconstituted distally. Group II patients (n = 143, with 205 subtotally occluded coronary arteries) had 50% to 99% proximal stenosis of at least one coronary artery. Cineangiograms were blindly reviewed to measure the size of the coronary arteries, which were compared with the actual vessel size at operation. In group I, the totally occluded coronary arteries had a cineangiographic size of 1.9 +/- 0.7 mm and an actual size of 1.6 +/- 0.4 mm (p = 0.00004). In group II, the subtotally occluded coronary arteries had a cineangiographic size of 1.8 +/- 0.4 mm compared with an actual size of 1.8 +/- 0.3 mm (p = not significant). The site of bypass grafting was significantly smaller in group I (1.6 +/- 0.4 mm versus 1.8 +/- 0.3 mm; p = 0.00008). The two groups were similar with respect to preoperative and intraoperative parameters. Operative mortalities were similar (group I, 1.8%; group II, 3.5%; p = 0.68). Creatine kinase isoenzyme profiles and electrocardiographic changes were similar, except for a significant late rise of creatine kinase-MB in group I (56.1 +/- 14.7 versus 30.7 +/- 33.7 MIU/mL; p < 0.001). In conclusion, cineangiography significantly overestimates the size of totally occluded coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417282 TI - Role of open lung biopsy in diagnosing pulmonary complications of AIDS. AB - Over a 4-year period, 25 patients with pulmonary complications of acquired immunodeficiency syndrome underwent open lung biopsy for diagnosis. Results of the biopsy led to a change in therapy in 15, and of this group, 8 patients improved clinically and were discharged. We believe that a select group of acquired immunodeficiency syndrome patients with pulmonary disease will benefit from open lung biopsy. Our indications for open lung biopsy are (1) a nondiagnostic bronchoscopy, (2) failed medical therapy after a diagnostic bronchoscopy, (3) failed empiric medical therapy after a nondiagnostic bronchoscopy or after a second nondiagnostic bronchoscopy, and (4) when any of the forementioned are accompanied with a worsening chest roentgenogram. Patients with acquired immunodeficiency syndrome who have a deteriorating respiratory status or require mechanical ventilation should not undergo open lung biopsy. PMID- 1417283 TI - Tetralogy of Fallot: favorable outcome of nonneonatal transatrial, transpulmonary repair. AB - This report describes our experience with 366 patients who had a transatrial, transpulmonary repair of tetralogy of Fallot between December 1980 and December 1991. Included in this group are patients with tetralogy of Fallot plus atrioventricular septal defect as well as patients displaying all degrees of aortic override (in the presence of subaortic ventricular septal defect and right ventricular outflow tract obstruction). Median age was 15.3 months and median weight, 12.3 kg. Of the 366 patients, 72% required a pericardial patch to reconstruct the main pulmonary artery or right ventricular outflow tract. Serious coronary anomalies were seen in 11 patients, without influencing surgical approach. There were two hospital deaths (0.5%; 70% confidence limits, 0.2% to 1.2%). Actuarial survival was 97.5% at 42 months (95% confidence limits, 95% to 99%) reflecting four late deaths over 1,129 patient-years of follow-up. Postoperative cardiac catheterization studies were performed in 61 patients at a mean follow-up interval of 23 months. Mean right ventricular/left ventricular systolic pressure ratio after repair was 0.46 (standard deviation, 0.28), and mean gradient across the right ventricular outflow tract was 15 mm Hg (standard deviation, 24 mm Hg). Actuarial freedom from reoperation for any reason has been 95% (95% confidence limits, 92% to 97%) at 5-year and 10-year follow-up. These early and medium-term results encourage us to continue with transatrial, transpulmonary repair of tetralogy of Fallot. We believe that this approach has an operative risk similar to or lower than transventricular repair, and that it will result in better preservation of right ventricular function in the long term. PMID- 1417284 TI - Benefits of combined balloon pumping and percutaneous cardiopulmonary bypass. AB - Sixteen patients (2 women, 14 men) aged 29 to 72 years with continued cardiogenic shock during intraaortic balloon pumping (IABP) had additional treatment with percutaneous cardiopulmonary bypass (PBY). Cause of cardiogenic shock was myocardial infarction in 7 (3 survived), failed percutaneous transluminal coronary angioplasty requiring emergency coronary artery bypass grafting in 5, postoperative aortic valve replacement in 1, postoperative emergency coronary artery bypass grafting in 1, after cardiac transplantation in 1, and bridging to transplantation in 1. Mean blood pressure with PBY and IABP combined was 75 mm Hg versus 60 mm Hg with IABP off. Percutaneous cardiopulmonary bypass flows ranged from 0.8 to 2.1 L/min with a mean flow of 1.3 L/min. Time on IABP ranged from 24 hours to 1 week. Time on IABP to PBY ranged from 1 to 20 hours, and time on PBY ranged from 65 minutes to 20 hours. Ten of 16 (63%) were successfully weaned, and 3 died after weaning. Seven of 16 (44%) survive. Combined IABP with PBY appears to be a better therapy than either one individually. Staging the therapy as the balloon first in and last out appears to be a good methodology. PMID- 1417285 TI - Coronary artery bypass using internal mammary artery branches. AB - The excellent long-term patency rates achieved with use of the internal mammary artery (IMA) to bypass the left anterior descending coronary artery have stimulated a variety of approaches to expand the use of this conduit in coronary bypass surgery. In this report we document our results using the two terminal branches of the IMA to bypass two arteries in a Y configuration. Sixty-seven patients received IMA Y grafts during a 6-month period in 1987. A total of 150 IMA branch anastomoses were performed (8 patients received bilateral IMA Y grafts). Fourteen of 67 patients were revascularized using IMA grafts only. Operative mortality was 2 of 67 (3%), and follow-up mortality was 5 of 67 (7.5%). Fifty-eight patients could be evaluated 37 +/- 2.7 months later. Clinically 36% of patients reported some recurrence of angina and 12 of 47 (25%) had a positive electrocardiographic stress test. Four patients were reoperated on (2 redo coronary artery bypass grafting, 2 transplants). Sixty (40%) of the 150 branch anastomoses could be evaluated objectively and 30 (50%) were patent. Five (8.5%) were stenotic and 25 (41.5%) were occluded (overall patency rate, 58.5%). We conclude that although the use of IMA Y grafts is a technically feasible means to increase IMA usage, extended application of this technique cannot be recommended unless improved patency rates can be demonstrated. PMID- 1417286 TI - Isolated biventricular working rat heart preparation. AB - The isolated perfused heart from small animals has been used extensively for hemodynamic and metabolic studies. The left working heart preparation proved superior to the Langendorff model for functional evaluations but has not allowed study of right heart function. A simple and inexpensive biventricular working heart preparation has been developed by modifying the left working rat heart model. Under general anesthesia the heart was removed surgically leaving sufficient vessels attached to it. Cannulation of the aorta, left atrium, right atrium, and pulmonary artery was completed in 10 minutes. A pressurized compliance chamber allowed rapid and reliable regulation of aortic impedance. For the 7 hearts that were subjected to 3-hour biventricular perfusion (their end points expressed as percent of their initial values), the aortic output (95% +/- 3%), pulmonary flow (88% +/- 9%), mean aortic pressure (109% +/- 5%), mean pulmonary pressure (100% +/- 2%), heart rate (106% +/- 8%), myocardial adenosine triphosphate level (85% +/- 8%), and creatine phosphate level (89% +/- 4%) were all maintained at physiologic levels. For the 11 hearts that were converted from left working heart preparation to biventricular working mode, significant improvement in stroke volume, aortic and cardiac output, and pressure development were observed. Experimental results indicate that the biventricular working model for isolated perfused rat hearts is superior to the left working preparation for studying the function of the total heart. Further study of the biventricular perfused working rat heart appears warranted. PMID- 1417287 TI - Effect of prostaglandin I2 and superoxide dismutase on reperfusion injury of warm ischemic lung. AB - A prostaglandin I2 (PGI2) analogue and superoxide dismutase (SOD) were administered to dogs with pulmonary denervation, and their effects on warm ischemic damage to the lung were studied. Twenty-seven adult mongrel dogs were divided into a control group (6 dogs), a PGI2 group (7 dogs), an SOD group (6 dogs), and a heparin group (8 dogs). The left pulmonary hilum was dissected, with PGI2 (1 microgram/kg) being administered to the PGI2 group and heparin (100 U/kg) to the heparin group. Then the left lung was placed in a warm ischemic state for 1 hour. The SOD group also received 20 mg/kg of SOD intravenously 1 minute before reperfusion. Before warm ischemia, immediately after reperfusion, and 1 hour and 2 hours afterward, the blood gases, left pulmonary vascular resistance, and other data were measured under right pulmonary artery clamping. Arterial oxygen tension showed significantly better values in the SOD and PGI2 groups than in the control and heparin groups. The left pulmonary vascular resistance increased with time in the control group but did not increase in the PGI2 group. Pulmonary microangiography showed that dilatation of the pulmonary arterioles was prominent in the PGI2 group. The quantity of pulmonary extravascular fluid was significantly less in the PGI2 and SOD groups than in the control and heparin groups. Histological examination showed marked collapse of capillaries, intraalveolar hemorrhage, and edema in the control and heparin groups, whereas these changes were only slight in the PGI2 and SOD groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417288 TI - Comparison of 180-degree and 360-degree skeletal muscle nerve cuff electrodes. AB - Use of skeletal muscle for cardiac augmentation is a promising technique for treatment of end-stage cardiac failure. An electrode woven through the latissimus dorsi that recruits nearby nerve fibers is commonly used to pace skeletal muscles both in clinical practice and in the laboratory. A proximally placed nerve cuff electrode offers potential advantages in improved recruitment of muscle fibers and low threshold for stimulation. We tested the effectiveness of a nerve cuff electrode passed directly about the proximal thoracodorsal nerve. Our report looks at the efficacy of nerve cuff electrode stimulation and compares electrical and histologic characteristics of a 180-degree wrap of the thoracodorsal nerve to a 360-degree wrap in dogs over 3 months. Threshold voltage at the commonly used pulse width of 200 microseconds was typically in the range of 400 to 600 mV for each electrode after 3 months. Statistical analysis revealed no significant difference (p < 0.05) in threshold voltage or current between the 180-degree and 360-degree nerve cuff electrode either at acute evaluation or after 3 months. Even contraction of latissimus dorsi was achieved with all implants. Adenosine triphosphatase staining revealed 100% conversion of type II to type I fibers in all stimulated muscles. Histologic examination of the thoracodorsal nerve and latissimus dorsi muscle revealed no abnormalities grossly or by light microscopy. Thus, a carefully applied nerve cuff electrode is an atraumatic, effective method for skeletal muscle stimulation. The 180-degree and 360-degree nerve cuff configurations are equally effective. PMID- 1417289 TI - Technique of open distal anastomosis for repair of descending thoracic aortic aneurysms. AB - Ischemic injury to the spinal cord and kidneys continues to be the major complication after resection of aneurysms involving the descending and proximal abdominal aorta. Our recent surgical experience with use of only a proximal clamp on the aorta to perform an "open" distal anastomosis has proved this technique to be safe and expeditious. We therefore compared our results using the technique of open distal anastomosis for aneurysm repair with those of the conventional two clamp technique. Since January 1989, we have used the conventional two-clamp technique in 31 patients (group 1) and the technique of open distal anastomosis in 24 patients (group 2). No significant differences were noted between the two groups in terms of age, sex, cause of aneurysm, extent of aneurysm, or site of proximal cross-clamp. The average distal ischemic time was 31 minutes in group 1 patients and 26 minutes in group 2 patients. Renal insufficiency occurred in 8 of 31 patients in group 1 and in 0 of 24 patients in group 2 (p = 0.01). Neurologic complications occurred in 4 patients in group 1 and in 1 patient in group 2. Early mortality rates were similar for both groups (4 of 31 [13%], group 1; 4 of 24 [17%], group 2). Deaths were attributed to multiorgan failure and sepsis in 6 patients and coexisting coronary artery disease in 2 patients. Based on these results, we believe the technique of open distal anastomosis is safe and may improve the outcome in patients undergoing operation for descending thoracic aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417290 TI - Extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. AB - A technique for extrapleural pneumonectomy in diffuse, malignant, pleural mesothelioma is described. The technique used in a protocol at Brigham and Women's Hospital has resulted in improved operative mortality figures and length of hospital stay. The right-sided procedure is presented followed by differences in technique required by the left-sided approach. PMID- 1417291 TI - Considerations in the skeletonization technique of internal thoracic artery dissection. AB - Skeletonization of the internal thoracic artery during myocardial revascularization procedures may provide some degree of protection from sternal wound infection in diabetic, obese, or pulmonary compromised patients when both internal thoracic arteries are used as conduits. Prior descriptions of the technique fail to provide specific details and possible pitfalls of the dissection. A method of skeletonization that has been used at the California Center for Cardiothoracic Surgery in more than 1,000 patients is presented in detail. Potential advantages and disadvantages are discussed. PMID- 1417292 TI - The Meadox-Gabbay pericardial xenograft: failure of the unicusp principle. AB - Durability of a new bioprosthesis, the Meadox-Gabbay unileaflet pericardial xenograft, was evaluated by reviewing a series of 12 patients who received this device in the mitral position from 1983 to 1985. Bioprosthetic failure necessitated reoperation in 5 patients 21, 22, 53, 66, and 81 months after placement. Three patients died of cardiac failure after 31, 52, and 70 months; no postmortem examinations were done. In 2 of the 3 patients, an echocardiographic study had shown signs of valvular dysfunction. Pathological examination of five available explants revealed the presence of redundancy and stretching of the single pericardial leaflet in all of them; in one, this lesion alone caused severe prosthetic incompetence. Other pathological findings included cusp and commissural calcification and commissural tears with or without calcification. Histologic examination and electron microscopy showed intrinsic calcification involving both collagen bundles and cellular debris and various degrees of collagen disruption. In this limited series of patients, the Meadox-Gabbay pericardial xenograft demonstrated various modes of failure that markedly impair its durability and render it unsuitable as a cardiac valve substitute. PMID- 1417293 TI - Comparison of cardiac output measured by intrapulmonary artery Doppler, thermodilution, and electromagnetometry. AB - A Doppler pulmonary artery catheter system (Doppler cardiac output monitor or DOPCOM) that continuously measures instantaneous and mean cardiac output was recently introduced. Because thermodilution (TD) flow measurements may not represent an adequate standard, the present study was designed to compare TD and DOPCOM cardiac output measurements with aortic electromagnetic (EM) flow in cardiac surgical patients. Twenty-one patients scheduled for elective coronary artery bypass grafting were enrolled in the study. Simultaneous measurement of cardiac output by all three methods was performed before cardiopulmonary bypass, after cardiopulmonary bypass with the aorta cannulated and volume intermittently infused, and after decannulation. Analysis of all data demonstrated fair TD and EM correlation (r = 0.80), with minimal bias (0.03 +/- 1.21 L/min) and a median absolute error of 0.53 L/min; DOPCOM and EM data showed moderate correlation (r = 0.64), a bias of -0.61 +/- 1.50 L/min, and a median absolute error the same as TD (0.51 L/min). However, distribution of DOPCOM values was heavily skewed by 3 patients in whom flow measurements immediately after cardiopulmonary bypass were markedly different between the DOPCOM and electromagnetometry, probably because of malposition of the Doppler transducers secondary to partial catheter withdrawal during bypass. Consistent with this theory was the finding that before CPB, the DOPCOM was significantly better than TD in predicting EM flow (median absolute error: DOPCOM, 0.12 L/min, and TD, 0.48 L/min; p = 0.04). Our data suggest that, in general, the DOPCOM shows similar precision to TD for predicting EM flow measurements, although the DOPCOM may underestimate actual flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417294 TI - Pulmonary artery sling. AB - Eighteen patients who underwent surgical treatment of pulmonary artery sling at this institution since 1969 were reviewed. Four of them had associated tracheal stenoses produced by complete cartilaginous rings (stovepipe trachea). All patients underwent operation. The median age at operation was 180 days (range, 27 days to 54 months). In the 14 patients with isolated pulmonary sling, the operation consisted of division of left pulmonary artery and reimplantation into the main pulmonary artery anterior to the trachea. In the 4 patients with stovepipe trachea, the stenotic tracheal segment was resected on cardiopulmonary bypass and the left pulmonary artery was brought anterior to the trachea before the latter was reanastomosed to the main pulmonary artery. There were no early deaths. One patient died late. The pulmonary artery anastomosis was patent in all 14 patients investigated postoperatively. Three patients have residual tracheobronchial problems. One patient is mentally retarded and is institutionalized. All other patients are symptom-free and growing normally and have normal chest radiographs. PMID- 1417295 TI - Pulmonary artery sling with tracheal stenosis: primary one-stage repair in infancy. AB - Pulmonary artery sling is often associated with tracheal stenosis. In many cases repair of the vascular anomaly alone does not relieve dyspnea. Primary one-stage repair with long segment tracheal resection (2.4 cm) and relocation of the left pulmonary artery using cardiopulmonary bypass and deep hypothermic circulatory arrest is described in a 6.5-month-old girl weighing 6.5 kg. This technique resulted in normal ventilation and pulmonary flow distribution. PMID- 1417296 TI - True aneurysm of the saphenous vein graft stump associated with CABG in a cardiac transplant patient. AB - Aneurysm of a saphenous vein graft after coronary artery bypass requires surgical resection because of its potential for rupture. This report describes a case of aneurysm formation in a 55-year-old man who underwent coronary artery bypass operation in 1977 and orthotopic heart transplantation 7 years later. A proximal vein graft remnant that had been ligated at the time of transplantation developed into a 5-cm aneurysm. In patients who have undergone previous coronary artery bypass operation, we recommend that the entire vein graft stump be excised and oversewn at the aortosaphenous anastomosis at the time of transplantation. PMID- 1417297 TI - Chronic, traumatic pseudoaneurysm of the ascending aorta. AB - Rupture of the ascending aorta is lethal in virtually all cases. In the recent literature, fewer than 9 cases of chronic, traumatic pseudoaneurysm of the ascending aorta have been documented. Reported herein is such a case, discovered incidentally and repaired successfully under cardiopulmonary bypass using a graft prosthesis. Aortogram remains the diagnostic method of choice in these patients. PMID- 1417298 TI - Aneurysm of the ascending aorta after cardiac transplantation. AB - We report the case of a 57-year-old female cardiac transplant patient in whom an aneurysm of the recipient side of the ascending aorta developed 1 year after transplantation. Although a mycotic origin was the likely cause, histologic examination diagnosed an atherosclerotic aneurysm. PMID- 1417299 TI - Simplified correction of outflow obstruction after mitral valve replacement. AB - Left ventricular outflow tract obstruction after mitral valve replacement may occur when a retained native anterior leaflet prolapses between prosthetic struts. Existing reports of left ventricular outflow tract obstruction by this mechanism lack emphasis on its surgical treatment. We obtained definitive relief of left ventricular outflow tract obstruction by transaortic exposure, division, and partial excision of the obstructing leaflet. This approach minimizes the complexity and potential morbidity of the correction. PMID- 1417301 TI - Total correction of transposition of great arteries with atrioventricular septal defect. AB - A successful anatomical correction of transposition of the great arteries with an atrioventricular septal defect is reported. This combination of anomalies is rare, and the anatomical correction is unusual in that the operation involves all four heart valves. PMID- 1417300 TI - Bronchoenteric fistula from an infected internal cardioverter defibrillator. PMID- 1417302 TI - New surgical technique for total-defect aortopulmonary window. AB - A new technique is described to repair aortopulmonary window with total defect in an 8-day-old baby. Because we expected the future growth of aorta, we used the anterior wall of the pulmonary artery as a large flap to reconstruct the posterolateral aortic wall. An equine pericardial patch was used to repair the defect in the pulmonary artery. This is a logically effective method for aortic reconstruction in a neonate with a large aortopulmonary septal defect. PMID- 1417303 TI - Newly developed holder for a right-angled metal venous cannula. AB - A newly developed holder for a right-angled metal venous cannula was developed to make direct insertion into each cava easier, especially insertion into the superior vena cava in pediatric open heart operations. We have been using this holder with ease and safety in all cases of small babies. PMID- 1417304 TI - Modified urinary collecting bags for prolonged underwater chest drainage. AB - We describe a method by which a modified urinary collecting bag is used as part of a chest drainage system. This system is especially suitable for patients who require prolonged periods of drainage. PMID- 1417305 TI - Clarence Crafoord and the first successful resection of a cardiac myxoma. AB - In 1954 Clarence Crafoord, the pioneer Swedish cardiovascular surgeon, removed an intraatrial myxoma for the first time. The patient was a 40-year-old woman with atypical symptoms of mitral stenosis. Follow-up 38 years later finds the patient alive and well. This case represents not only the first extirpation of a cardiac tumor on cardiopulmonary support but also the dawn of open cardiac surgery in Sweden. Others were soon to follow the lead of Crafoord and his team. However, their bold efforts prepared the way for the early diagnosis and facile extirpation of cardiac myxomas. Moreover, this group played an integral part in the development of safe, effective cardiopulmonary perfusion. PMID- 1417306 TI - [Consumption of amino acids by Escherichia coli--a producer of recombinant proteins]. AB - The dynamics of amino acid consumption from the medium by Escherichia coli 1864, a strain producing recombinant protein was studied. It was shown that the strain actively used glutamate and aspartate from the medium, which was determined by the leading role of the amino acids in nitrogen metabolism. The strain also consumed threonine, glycine and alanine capable of effectively providing the culture with metabolic energy. PMID- 1417307 TI - [Isolation of protoplasts of Xanthomonas rubrilineans and their use in the study of localization of aminopeptidases]. AB - The culture of Xanthomonas rubrilineans was able to synthesize a number of intracellular aminopeptidases. To study localization of the enzymes in the cells, a protoplasting procedure was developed providing the yield of 99.7 per cent. The following subcellular fractions were isolated: periplasmic, cytoplasmic and membranous. It was shown that alanine aminopeptidase was a cytoplasmic enzyme and glutamate peptidase was a membrane-bound enzyme. PMID- 1417308 TI - [Relation between the morphogenesis of Xanthomonas rubrilineans and biosynthesis of aminopeptidase in the process of growth and development of its producer]. AB - The dynamics of growth and development of Xanthomonas rubrilineans, a culture producing intracellular aminopeptidase, was studied. A difference between the growth rate determined by intensity of the total biomass accumulation and the rate of the culture multiplication was found. The difference was due to the presence of two phases in the culture development during the exponential growth: the phase of increasing the linear sizes of the cells and the phase of the culture intensive multiplication. The most intensive synthesis of aminopeptidase was observed during the phase of increasing the linear sizes of the cells. The dynamics of consumption of the main sources of carbon and nitrogen by the culture was investigated. PMID- 1417309 TI - [Use of analogs of primary metabolites in the selection of the producer of polymyxin B]. AB - A number of amino acids were found to have effects on the growth of the polymyxin B-producing culture and biosynthesis of the antibiotic by it. Of special importance was the stimulating effect by methionine. Four selection stages were carried out with using structural analogs of purines and amino acids as selective factors. There were no stable variants with increased antibiotic productivity among the mutants resistant to the analogs of purines and leucine. The levels of polymyxin B accumulation by the variants resistant to 4-fluorophenylalanine were 30 to 50 per cent higher than those in the controls and the variants were characterized by low morphological and antibiotic production variation in the subcultures. The mechanisms of the methionine physiological effect and the prospects of using analogs of the primary metabolites in improvement of the culture producing polymyxin B are discussed. PMID- 1417310 TI - [Incorporation of an antineoplastic drug aclarubicin into liposomes in relation to the conditions of its encapsulation]. AB - The results of liposome drug encapsulation of aclarubicin (aclacinomycin A), an antitumor antibiotic, are presented. The method of flow detergent dialysis was applied. Conditions providing maximum encapsulation of aclarubicin (the ratio of lipid components and the lipid/detergent ratio), as well as conditions providing stability of liposomal emulsion (the presence of antioxidants, stearic acid and cholesterol) were defined. PMID- 1417311 TI - [Amikacin resistance of clinical strains of Enterobacteriaceae and Pseudomonas]. AB - Amikacin resistance was studied in 380 bacterial strains of Enterobacter, Klebsiella, Serratia, Pseudomonas and E. coli isolated in clinics of the Moscow Region. It was shown that 69 isolates were resistant to amikacin. Plasmid DNA was detected in 10 amikacin resistant isolates. Three of them belonging to Klebsiella and 3 belonging to E. coli contained plasmids controlling resistance to amikacin. The plasmids isolated from the strains of Klebsiella determined as well resistance to kanamycin and streptomycin but did not control resistance to sisomicin, tobramycin and gentamicin while the plasmids isolated from the strains of E. coli determined resistance to amikacin, kanamycin, gentamicin, tobramycin and sisomicin. PMID- 1417312 TI - [Pleiotropic nature of mutation of resistance to 2,3,5-triphenyl- tetrazolium chloride of Francisella tularensis]. AB - Natural strains of F. tularensis were characterized by sensitivity to 2,3,5 triphenyl tetrazolium chloride (TTC). Development of TTC resistance in the cells of F. tularensis was accompanied by changes in the biological properties of the culture, i.e. the colony morphology, antigenic structure, virulence and immunogenicity for laboratory animals. Moreover, there was a direct correlation between the levels of TTC resistance and resistance to chloramphenicol, erythromycin, tetracycline, furazolidone and rifampicin. The antibiotic resistant mutants of F. tularensis were in turn more resistant to TTC than the initial strains. This could be useful in isolation of polymarked strains of F. tularensis for genetic studies and investigation of the nature of the phenomenon of virulence in F. tularensis. PMID- 1417313 TI - [Comparison of therapeutic effects of antibiotics of the tetracycline group in the treatment of anthrax caused by a strain inheriting tet-gene of plasmid pBC16]. AB - In vivo and in vitro efficacy of tetracyclines was studied with respect to anthracic infection induced by a tetracycline-resistant resistant strain containing plasmid pBC16. The plasmid-containing strain was resistant to tetracycline, doxycycline and minocycline, the MICs exceeding those for the initial strain 500, 640 and 80 times, respectively. There was no therapeutic effect of tetracycline and doxycycline in the treatment and urgent prophylaxis of anthracic infection caused by the tetracycline-resistant strain of Bacillus anthracis. High therapeutic efficacy of minocycline in the average therapeutic concentrations was shown irrespective of the contaminating doses and strains. Minocycline was recommended for treatment and urgent prophylaxis of anthracic infection caused by tetracycline-resistant B. anthracis strains. PMID- 1417314 TI - [Clinical pharmacokinetics of kanamycin in endolymphatic therapy of peritonitis]. AB - The pharmacokinetics of kanamycin in patients with peritonitis was studied after its intramuscular, endolymphatic and lymphotropic administration. Endolymphatic administration of kanamycin provided an increase in its activity in the inflamed tissues of the peritoneum and omentum and markedly prolonged its halflife as compared to those after the routine intramuscular administration of the drug. Lymphotropic administration of kanamycin failed to provide the same effect. Endolymphatic therapy of the patients during the postoperative period provided a decrease in the lethality, development of complications and the terms of the treatment in the hospital. The therapeutic effect of the endolymphatic administration of kanamycin to the patients with peritonitis proved to be high. The more efficient antibiotic therapy of the cases was likely due to favourable shifts in the pharmacokinetics of kanamycin after its endolymphatic administration. PMID- 1417315 TI - [Antibiotic therapy in acute diffuse peritonitis]. AB - The pharmacokinetics and clinical efficacy of antibiotics administered by various routes in acute diffuse peritonitis were studied on 25 non-inbred dogs and potential of lymphotropic administration of the antibiotics through the mesentery of the small intestine in urgent surgical operations because of the diseases of the abdominal cavity was estimated. It was shown that the intra-mesenteric administration of the antibiotics was more efficient. In acute diffuse peritonitis it provided high therapeutic concentrations of gentamicin in the central lymph and lymph nodes of the abdominal cavity. PMID- 1417316 TI - [Immunologic correction with immunoglobulin of toxemia with exicosis in infants with acute intestinal infections]. AB - The clinical course of acute intestinal infections complicated by toxicosis and exicosis was studied in 150 infants undergoing multimodality therapy, including natural human immunoglobulin for intravenous injections. The use of the new complex in the treatment of intestinal toxicoses was accompanied by increasing host immunological reactivity within short periods and decreasing of the treatment duration by 5.0 +/- 1.3 days; there were no persisting and chronic forms of the diseases and fatal outcomes. It was concluded that the use of the immunoglobulin for intravenous injections in the multimodality therapy of intestinal toxicoses in infants made it possible to prevent death in complicated intestinal infections and at the same time to accelerate their recovery. PMID- 1417317 TI - [Chloramphenicol (levomycetin) in the current therapy of bacterial infections]. PMID- 1417318 TI - [Fundamental bases for producing new effective antibiotics]. PMID- 1417319 TI - [A cassette micromethod of determining the sensitivity of anaerobic microorganisms to antimicrobial drugs]. AB - A micromethod based on the use of plates with wells and microquantities of microbial suspensions is described. It provides determination of MICs of antibacterial drugs and sensitivity of clinical strains of anaerobes of 2 or 3 species predominating in pathological materials as well as to preliminarily identify some anaerobic bacteria by their antibiotic sensitivity. PMID- 1417320 TI - [Elaboration of a rapid method of determining the sensitivity of Brucella to antibiotics]. AB - Optimal conditions were developed for determination of antibiotic sensitivity in Brucella by using enzyme immunoassay directly in the primary cultures of the material tested. The Brucella concentration in the material tested should be not lower than 1.10(6) microbial cells/ml and the time of culture incubation be 24 hours at 37 degrees C. The obligatory condition is to use a liquid medium, i.e. the Albimi broth with 1% glucose. To inhibit the foreign microflora it is recommended to use polymyxin B and amphoglucamine in a concentration of 3 microgram/ml. The use of enzyme immunoassay was shown that it was possible to determine the antibiotic sensitivity of Brucella in practice. PMID- 1417321 TI - [Effect of doxycycline on leukocyte adhesion in a multifactorial experiment]. AB - The multifactorial analysis was applied to study the effect of doxycycline on leukocyte adhesion to a plastic within wide ranges of the values of experimental factors such as doxycycline concentrations and magnesium and calcium ions. The data were computer-processed and second-order equations characterizing the influence of the factors on adhesion were derived. It was shown that the effect of the ions on adhesion was non-single-valued; accurate quantitative models describing the ion effect on adhesion were developed when the concentration of doxycycline was changed. PMID- 1417322 TI - [Biochemical indicators of anthracycline sensitivity of blast cells from patients with hemoblastoses]. AB - It was shown that accumulation of adriamycin (ADR) and its impact on DNA synthesis in the blast cells of patients with hemoblastosis studied under conditions of short-term incubation correlated with the antileukemic activity of anthracyclines. The combination of the two biochemical and pharmacological indices, i.e. the high levels of ADR accumulation and inhibition of DNA synthesis, is may useful in solving the problem on inclusion of the antibiotics to the schemes of combined chemotherapy of patients with hemoblastosis. PMID- 1417323 TI - [Use of Hoechst fluorescent probe 33258 for quantitative analysis of intracellular binding of anthracycline antibiotics to DNA]. AB - The paper deals with development of a procedure for quantitative determination of the share of anthracycline antibiotics bound in cells directly to DNA. A DNA specific Hoechst fluorescence dye 33258 was used for the purpose. The level of its quenching on DNA correlated with the quantity of the antibiotic bound to it. It was shown that the quenching of the Hoechst fluorescence dye bound to DNA was not due to the dye competition with the antibiotic for the site of bounding on DNA, as was suggested earlier. It was likely to be defined by reabsorption of the radiation by antibiotic molecules. PMID- 1417324 TI - [Effect of doxycycline on immune response in a multifactorial experiment]. AB - Multifactorial analysis was applied to studies on the effect of doxycycline on the primary immune response to sheep erythrocytes. The experimental factors were the following: the antibiotic dose, the antigen dose and the time of the onset of the antibiotic therapy with respect to the antigen action. Polynomial statistic models describing the delayed hypersensitivity and antibody titers within wide ranges of factor values were designed by the experimental data. It was shown that the prophylactic use of doxycycline prior to the antigenic stimulus markedly lowered the high-dose tolerance induced by high doses of the antigen. PMID- 1417325 TI - [Antibiotics of the aminoglycoside group (gentamicin, sisomicin and amikacin) in the prevention and treatment of experimental plague]. AB - Activity of aminoglycosides such as gentamicin, sisomicin and amikacin against plague microbe strains of natural origin was studied in vitro. It was also studied in prophylaxis and treatment of experimental plague infection in albino mice. The MAC of gentamicin and sisomicin for 50 strains of the plague microbe was 0.2-1.6 micrograms/ml. For the majority of the strains it was 0.4 micrograms/ml. The amikacin MICs were 0.4-3.2 and 0.8 micrograms/ml, respectively. High efficacy of gentamicin, sisomicin and amikacin was shown in prophylaxis and treatment of experimental plague infection in albino mice. The optimal doses of the antibiotics were determined. Under definite conditions such as the use of short-term regimens and higher intervals, advantages of sisomicin over gentamicin and amikacin in prophylaxis of experimental plague infection were observed. PMID- 1417326 TI - [Late effects of damaging action of doxorubicin on the reproductive system and progeny of rats]. AB - The effect of doxorubicin, an anthracycline antibiotic, on the reproductive system and progeny was studied in rats 1 month after a single administration of the drug in the MID of 6.85 mg/kg. It was shown that doxorubicin induced a decrease in the number of the mature oocytes in the rat ovary and an increase in the pre- and post-implantation death rate. The rats exposed to the antibiotic 1 month before the mating with intact male rats had unchanged fertility and pregnancy. In the fetuses isolated from the female rats treated with the antibiotic, development of some parts of the skeleton appeared to be retarded. One fetus and one young rat had severe developmental anomalies in the skeletons: shorter right anterior and hind extremities and finger aplasia. The survival rate of the progeny from the female rats exposed to the antibiotic was markedly decreased. No retardation in the physical development of the progeny was observed. PMID- 1417327 TI - [Prevention of early inflammatory complications after transthoracic interventions and estimation of the degree of immunologic deficiency]. AB - An analysis of the results of the examination and treatment of 379 patients undergoing transthoracic interventions showed that the use of the target-aimed selective immunomodulation, short-term antibacterial prophylaxis, inhibitors of arachidonic acid metabolites, active elimination of the circulating immune complexes and medium-weight molecular peptides and adequate local analgesia after the interventions providing normalization of the laryngeal reflex and early activation of the patients permitted the incidence of the pulmonary complications to be decreased by 2.5 times, pleural complications by 1.7 times, suppuration of the postoperative wound by 1.8 times and the total expenses by 25.6 per cent. PMID- 1417328 TI - [Lymphotropic antibiotic therapy of obstetrical suppurative-septic diseases]. AB - The pharmacokinetics and efficacy of gentamicin after its direct and indirect endolymphatic administration were comparatively studied. It was shown that the time course of the blood pharmacokinetics of the antibiotic was almost the same as under the both conditions. Therefore, in many cases the less complicated and more available indirect endolymphatic therapy may replace the direct labor consuming and traumatic endolymphatic administration of drugs. PMID- 1417329 TI - [Ways of increasing the effectiveness of chemotherapy of urinary tract infection]. AB - Efficacy of blood UV irradiation (BUVI) followed by its reinfusion to the patient in combination with antibacterial therapy was studied in patients with acute and chronic pyelonephritis and its purulent septic complications. The BUVI was used when the antibacterial drugs failed to be sufficiently efficient and the clinical process of the infection was severe. The kinetics of ferritin, transferrin, alpha 2-macroglobulin, beta 2-microglobulin and haptoglobulin in the blood serum was investigated as a criterion of treatment efficacy. It was shown that the BUVI markedly increased the chemotherapy efficacy. The observed regularities of the changes in the serum antigenic spectrum can be used as a basis for the control of treatment efficacy. PMID- 1417330 TI - [Ofloxacin and ciprofloxacin in the treatment of sexually-transmitted diseases]. AB - A complex clinico-laboratory++ examination and treatment were made of 76 women with inflammatory processes in the urogenital tract. Gonorrhea, trichomoniasis, chlamydiosis and Ureaplasma infection were detected in 60, 31.4, 41 and 14 per cent of the cases, respectively. There were affections of the rectum by gonococci, chlamydia, ureaplasmas and Trichomonas in 55, 32, 10.6 and 6.6 per cent of the cases, respectively. The frequency of chlamydia in the oropharynx amounted to 30 per cent whereas gonococci and ureaplasma were less frequent i.e. 9 and 1.2 per cent, respectively. The combination of the above pathogens in the rectum were the following: gonococci and chlamydia (15 per cent of the cases), gonococci, chlamydia and Trichomonas (7.3 per cent), gonococci and ureaplasma (7.3 per cent), ureaplasma and chlamydia (7.8 per cent). In the throat the association of gonococci and chlamydia was detected in 3.7 per cent of the cases. It should be indicated that the signs of sex-transmitted diseases were few, which required careful clinico-laboratory examination of the extragenital foci in the patients with inflammatory urogenital diseases. Ofloxacin showed a high efficacy in the treatment of patients with gonorrhea and ureaplasmosis. Its use in treatment of chlamydiosis proved inexpedient while ciprofloxacin was effective in the treatment of the infection. PMID- 1417331 TI - [Use of vilozen and ketotifen combination for increasing the effectiveness and prevention of complications of antibiotic therapy of streptococcal infections]. AB - The clinical efficacy of a vilozen and ketotifen (zaditen) combination in the treatment of streptococcal infections along with the routine therapy was studied. The use of the combination was shown advisable in the complex therapy and prevention of relapses in patients with streptococcal infections. The combined pharmacotherapy promoted better clinical indices, normalization of the immune status and a reduction in the incidence of allergic reactions to antibiotics and a decrease in sensitization to bacterial allergens. PMID- 1417332 TI - [Principles of antibiotic therapy in pulmonology]. PMID- 1417333 TI - [Electrotransformation of bacteria]. PMID- 1417334 TI - [Plasmid analysis of cadmium- and penicillin-resistant strains of staphylococci isolated in maternity hospitals]. AB - The plasmid analysis of a collection of the staphylococci isolated was made in the obstetric hospitals of Nizhny Novgorod and Arzamas in 1986-1989. It revealed the presence of large complex plasmids with a molecular weight of 22 MD carrying the determinants of resistance to penicillins and cadmium and mercury ions in polyresistant strains. Conjugation transfer of the plasmid even between the staphylococci of different species was performed under experimental conditions. It was suggested that occurrence of the strains carrying the complex cadmium penicillinase plasmid was due to violation of the sanitary or ecological requirements. PMID- 1417335 TI - [Antibiotic resistance of Lactobacillus strains]. AB - One hundred and thirty six Lactobacillus strains isolated from poultry and 23 Lactobacillus strains isolated from long-living persons were tested for their antibiotic sensitivity. Occurrence of some type determinants of resistance to aminoglycoside antibiotics and tetracyclines in the Lactobacillus strains resistant to these antibiotics was studied. The majority of the strains from the both collections were resistant to aminoglycosides (73 and 79 per cent, respectively). The isolates from the poultry were characterized by multiple resistance. The isolates from the long-living persons were most frequently resistant to one of two antibiotics. All the tested Lactobacillus strains isolated from the long-living persons were sensitive to tetracyclines. The species composition of the isolates was different. The antibiotic-resistant strains were detected in all the species involved in the study. By hybridization of Lactobacillus colonies with the probes containing various genes of the resistance it was shown that in 14 per cent of the antibiotic-resistant strains belonging to Lactobacillus the antibiotic resistance was controlled by the genes homologous to resistance genes widely distributed in gramnegative organisms. This indicated a possible wide exchange and heterologous expression of the antibiotic resistance determinants between microorganisms of various taxonomic groups. PMID- 1417336 TI - [Immunomodulating action of heteropolysaccharides isolated from camomile flowers]. AB - Administration of heteropolysaccharides from the camomile flower clusters to rats which failed to perform a physical load (swimming) resulted in stimulation of development of the immune response to SRBCs. However, it did not influence development of the immune response to a bacterial lipopolysaccharide in the rats. A short-term exposure of the swimming animals to high doses of the heteropolysaccharides increased development of the immune response induced by their lipopolysaccharide. A long-term exposure of the swimming rats to low doses of the heteropolysaccharides increased development of the immune response to SRBCs and the lipopolysaccharide. The high doses of the heteropolysaccharides induced excretion of the helper factors by the spleen cells not adhesive to glass while the low doses of the heteropolysaccharides decreased sensitivity of the cells of the immune system to the influence of the suppressing factor excreted by the glass-adherent spleen cells from swimming rats. PMID- 1417337 TI - [Characteristics of chemotherapy of infectious diseases associated with gunshot wounds and trauma]. AB - The experience in treating infectious diseases in wounded and traumatized persons from the contingent of the Soviet Troops in ++Afghanistan is described. The syndrome of the joint effect of the injury and infection is characterized. Features of the chemotherapy of the injured patients with viral hepatitis, malaria, typhoid fever and enteric and ++extra-enteric amebiasis under the ecological and professional stress and with an account of the etiology of the wound infection are presented. The favourable effect of the developed methods for chemotherapy of the joint affections was shown. PMID- 1417338 TI - [Rational chemotherapy of suppurative cholangitis]. AB - A complex bacteriological approach to the problem of purulent cholangitis was applied. Specimens of bile from 140 patients, gallbladder walls from 106 patients, liver tissue from 93 patients and peritoneum tissue from 82 patients were examined. It was microbiologically shown that the infectious process in the patients with purulent cholangitis involved not only the bile and gallbladder walls but also the surrounding tissues of the liver and peritoneum. There was a correlation between the bile microflora and the microflora of the surrounding tissues. The microflora of the bile, gallbladder walls, liver and peritoneum tissues was characterized qualitatively and quantitatively. Sensitivity of 494 clinical isolates to 16 antimicrobial drugs was assayed. To prevent the postoperative complications, schemes for the antibacterial therapy were developed with an account of the aerobic and anaerobic spectra of the microbes disseminating the bile, gallbladder walls, liver and peritoneum. PMID- 1417339 TI - [Effect of indirect endolymphatic antibiotic therapy on clinical and immunological indicators in patients with erysipelas of the lower extremities]. AB - Two groups of patients with erysipelas of the lower extremities underwent indirect endolymphatic therapy with bicillin-3 (58 patients) and routine penicillin therapy (79 patients). Comparative clinicoimmunological examinations in the two groups revealed that lymphotropic administration of the antibiotic had a more favourable effect on the disease process, as evidenced by more rapid reverse time courses of erysipelas clinical signs, less frequent incidence of early relapses and normalization of the majority of immunological parameters by the end of the treatment. For estimation of the anti-recurrence efficacy of the antibiotic therapy in the patients with erysipelas, it was recommended to use a specific scale based on the principles of the Wald successive alternative analysis. PMID- 1417340 TI - [Clinico-bacteriological evaluation of the effectiveness of piperacillin in suppurative-inflammatory diseases of the lungs and pleura]. PMID- 1417341 TI - [Age-related characteristics of ceftazidime pharmacokinetics in children]. AB - To reveal possible age-dependent variations in the ceftazidime pharmacokinetics, the drug plasma concentrations were determined by HPLC in 10 children aged 2 to 13 years with peritonitis. The blood specimens were collected 0.25, 0.5, 1, 3, 6 and 8 hours after intravenous bolus administration of ceftazidime (Kefadym, Eli Lilly) in a single dose of 20 mg/kg. The mean values of the model-independent parameters were: total clearance (Cl), 3.3 +/- 0.8 ml/min.kg; steady-state distribution volume, 0.32 +/- 0.06 ml/kg; mean residence time, 1.7 +/- 0.4 hours. The C-coordinate of the gravity center was equal to 26 +/- 7 mg/l. A noticeable age-dependent decrease in Cl was detected by comparing the Cl estimates in our study for the children aged 7.0 +/- 3.0 years with earlier findings in children aged 12 years as well as in adults (18 and 26 years) and elderly patients (77 years): 2.5, 2.2, 2.0 and 1.1 ml/min.kg, respectively. A similar trend was observed for the ceftazidime volume of distribution (Varea). Due to the described reduction in Cl and Varea the age-induced changes in the half-life of ceftazidime were negligible. The age-dependent differences in ceftazidime pharmacokinetics should be taken into account in designing rational dosage regimens for the drug administration. PMID- 1417342 TI - [Chemotherapy of Campylobacter infections]. AB - A total of 600 patients with suspected alimentary food poisoning were hospitalized. The ++clinico-laboratory findings showed that 27 (4.5 per cent) of them had Campylobacter infection. The cultures of Campylobacter jejuni and Campylobacter coli were isolated from 24 and 3 patients, respectively. The patients underwent complex pathogenetic treatment with oral rehydration saline solutions, symptomatic agents, enzymatic preparations and diet (the basic therapy) supplemented with biological bacterial preparations in less severe cases (8 patients). Antibacterial drugs such as furazolidone (roxytromycin), gentamicin and levomycetin, as well as fluoroquinolones such as ofloxacin and ciprofloxacin were additionally used in the treatment of both the patients with the generalized infection and those with more severe processes of the disease, pronounced diarrhea with blood traces and persisting isolation of Campylobacter (12 patients). The most favourable results in the treatment of more severe patients with Campylobacter infection were obtained with the fluoroquinolones used after inadequately efficient therapy with furazolidone or antibiotics especially in the cases with repeated isolation of campylobacteria. PMID- 1417343 TI - [Digestive tract as the main endogenous source of bacterial and fungal infections. The importance of maintaining colonization resistance]. PMID- 1417344 TI - [Rifampicin in present-day chemotherapy of bacterial infections]. PMID- 1417345 TI - [Physiological characteristics of the strains of Cryptococcus deffluens- producers of penicillin acylase]. AB - A fermentation medium balanced by the main components was developed for Cryptococcus diffluens strains producing penicillin-V-acylases (PA). It was shown that the culture needed for production of the enzyme was inductor, which was phenoxyacetic acid (POAA). Additional introduction of ethanol to the medium provided an increase in production of PA by 36 per cent and the culture growth by 25 per cent. Introduction of one of the following substances to the medium with POAA and ethanol i.e. (CN3COO)2Ca, FeSO4, proline or asparagine provided an additional increase in the production level of PA by 24 to 94 per cent. The use of the medium varieties will permit one to isolate highly productive cells of the culture. PMID- 1417346 TI - [Remembering Professor Chavez]. PMID- 1417347 TI - [Our world in the last few years of the 20th century and the millennium. Medicine and the physician]. PMID- 1417348 TI - [Echocardiographic study of heart remodelling in ischemic cardiopathy]. PMID- 1417349 TI - [Effect of lead and cadmium on platelet aggregation]. AB - Two heavy metals, lead and cadmium, are frequently found as pollutants in many systems. Their effect upon platelet aggregation was investigated, both in human and rat platelet rich plasma and washed platelets. ADP-induced aggregation of human platelets was inhibited by 50%, using concentrations of free lead between 2 4 mM and free cadmium between 0.05 and 0.2 mM. Rat platelets were about ten times more sensitive to the effect of lead than human PRP. 50% inhibition of epinephrine-induced aggregation was attained at lower concentrations of metal, than the concentrations needed for ADP-induced aggregation. The effect was more apparent upon the first phase, which was lengthened, both with PRP and washed platelets. The aggregation of human and rat washed platelets by calcium was inhibited by concentrations of the metals within micromolar ranges. When A 23187 was used as the aggregating agent, the inhibition by the metals was only partial. Cysteine, at approximately tenfold concentrations, reversed the effect of the metals. Cadmium appeared more effective than lead as an inhibitor of platelet aggregation in all systems. Since only high levels of metal inhibit aggregation, more sensitive organs or systems would show alterations, due to these metals at an earlier stage and at lower concentrations. PMID- 1417350 TI - [Analysis of rheumatic valvulopathy with scanning electron microscopy]. AB - There is a high incidence of rheumatic endocarditis in our environment. Therefore it is important to know the structural characteristics of the valvular lesions in order to better understand the physiopathologic pathways of tissue injury. We have chosen a non-conventional method, the scanning electron microscopy. There were very few such reports in the current literature. We analyzed ten mitral valve with rheumatic scarring lesion and five normal, as a control group. We were able to establish three structural patterns. 1) Stone pavement like (endocardium with nuclear bulge cells and marginal folds at the cell boundaries, abundant number of microvillous projections and few areas of endothelial loosening). 2) Cerebroid (subendothelium with wrinkles caused by deformity of the valve with or without endothelial loosening) and 3) Smooth pattern (flattened endothelium with scanty microvillous projections and abundant areas of endothelial denundation and exposition of subendothelium). More damage was noted in the auricular surface of the rheumatic group, characterized by a predominance of the smooth pattern. We found Lambl's excrecences in two mitral leaflets, they were formed by collagen break fascicles of the subendothelium. This technique allowed us to analyze integrity of the endocardial selective barrier and the interactions between the damaged surface of the valve and elements of the peripheral blood and showed more endocardial injury in the rheumatic group. These alterations could play an important role in the pathogenesis of this disease. PMID- 1417351 TI - [Late results of mitral valve replacement in 155 subjects under 16 years of age. Comparative study with 4 prosthesis]. AB - We followed 155 children aged 6 to 16 years who underwent mitral valve replacement for rheumatic heart disease. Group I included 74 patients with Starr Edwards prostheses and the mean follow-up period was 13 years. Group II was formed by 36 patients with Bjork-Shiley prostheses and a mean follow-up of 7.5 years. Group III consisted of 31 children with dura mater bioprostheses and a mean follow-up of 5.1 years. Finally, group IV included 14 patients followed a mean period of 4.9 years with Hancock xenografts. The four groups of patients were comparable before surgery. The criteria of the New York Heart Association (NYHA) were used to evaluate all patients before and 12 months after surgery. All patients with mechanical prostheses received anticoagulant therapy with acenocumarol from the first postoperative day. The incidence of complications such as thromboembolism, infective endocarditis, prosthetic dysfunction and death were determined at the end of the follow-up. The Fisher's exact test was used for nonparametric analysis and the two-tailed Student's T test for parametric results. All but two patients improved their NYHA clinical status after surgery (p less than 0.0001). Forty eight patients with mechanical prostheses were catheterized 1 to 7 years after the operation. The mean pulmonary arterial systolic pressure was reduced from 58 mmHg to 30 mmHg (p less than 0.001) and the mean pulmonary arterial wedge pressure decreased from 22 mmHg to 11 mmHg (p less than 0.001). There were no significant differences between the groups with mechanical and tissue prostheses in the incidence of thromboembolism and infective endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417352 TI - [Percutaneous transluminal angioplasty in aortic coarctation in adolescents and adults. Mid-term results]. AB - From October 1985 to February 1992 we performed 80 percutaneous transluminal angioplasty (PTA) in 76 patients with coarctation of the aorta (CoAo). Sixteen of them with ages ranging from 12 to 62 years (mean = 21.1). We describe the experience in these cases. Fifteen with native and one with post-surgical coarctation. The gradient decreased from 72 +/- 33 to 18 +/- 17 mmHg immediately after dilation, in the follow-up (1 to 69 months m = 25) was 23 +/- 20 mmHg. In one patient we performed simultaneously angioplasty of CoAo and mitral valvuloplasty with excellent results in both lesions. We redilated two cases for residual gradient successfully. We had one failure in a patient with long coarctation. He needed surgery. In the initial experience we had one severe complication (cerebral stroke). No deaths or aneurysms. In conclusion we believe that PTA is an adequate alternative in adolescents and adults with native or post surgical coarctation of the aorta with minimum incidence of complications. PMID- 1417353 TI - [Corrected transposition of the great arteries]. AB - Sixty-nine patients with Corrected Transposition of the Great Arteries were studied, with a mean age of 8.3 years. Forty-nine had atrial situs solitus (SS) and 20 atrial situs inversus (SI). The diagnosis was proved by echocardiography in 28 cases and in all by angiocardiography. In cases with SS, 29 presented ventricular septal defect (VSD), 20 had subvalvular pulmonary stenosis (SVPS), 13 tricuspid regurgitation (TR), 13 atrio-ventricular block (AVB), and seven without associated defects. In cases with SI, 13 had VSD, 14 SVPS, five IT, three AVB, and two without associated defects. The long-term follow-up of the atrioventricular (AV) conduction in 53 cases, ranging between 2 and 37 years (mean 8.3) showed at the beginning of the evaluation 37 cases with normal AV conduction, 14 with first degree AVB, and two with complete AVB. At the end of the follow-up 24 cases had normal AV conduction, 13 first degree, two second degree, four intermittent and 10 complete AVB. The contingency table showed that the possibility of developing changes of the AV conduction was greater in those cases who had an abnormality at the beginning with a relative risk of 2.27 (p = 0.03). Twenty-three cases had SVPS associated with VSD without significant symptoms. During a follow-up ranging from 1 to 20 years (mean 6.5 +/- 5.9), five of these patients were surgically corrected at ages from 6 to 11 years. The remaining cases have had a stable course. At the beginning of the study, 18 cases had TR, and it developed in five more patients during the same follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417354 TI - [Myocardial hypertrophy in aortic insufficiency as a compensation mechanism. Implications for surgical indication]. AB - We studied 24 patients with pure and severe aortic regurgitation. Using 2-D Echocardiography we obtained parasternal short axis view and calculate the thickness/radio (H/r) ratio and with apical four chambers and two chambers view the ejection fraction (E.F.) with biplanar Simpson technic. The patients were divided in three groups: I) those (12) with E.F. and H/r ratio within normal limits; II) those (6) with low H/r ratio and normal E.F. and the third group III) was formed with 6 patients whom had low H/r ratio and E.F. Three patients from group I had surgical treatment without mortality; all but one (bacterial endocarditis) are alive after two years; five patients from group II had surgical treatment and everyone is alive in functional class I in the same period. All patients of the third group III but one (that had surgical treatment) are death in spite of medical treatment. We conclude that the optimal moment for surgical procedure in severe aortic regurgitation can be determined when the hypertrophy does not compensate the hemodynamic overload (decreases H/r) but the cardiac performance (E.F.) is normal. In this moment the surgical mortality is low and the procedure can change the natural history of the disease. PMID- 1417355 TI - [Ruptured aneurysm of the aortic sinus of Valsalva: clinical course, diagnosis, and treatment]. AB - The authors present the clinical cases of 5 patients, with rupture of the aortic Valsalva's sinus aneurysm open to the right chambers, diagnosed clinically, echocardiographically and hemodynamically in the past eight months. Among them, four were males, and one female. Three were treated surgically successfully, one patient refused surgery and another had a sudden death before surgery. The patients showed arteriovenous blood flow shunt, three from the aorta to the right ventricle, and two to the right atrium. One case was associated to an atrial septal defect, and tricuspid insufficiency in another. The authors added a sixth case: a woman, with rupture of the aortic Valsalva's sinus open to the right ventricle, aortic insufficiency and diaphragmatic subaortic stenosis. The authors discuss the embryologic origin of the formation and rupture of the Valsalva's sinus aneurysm as well as the factors that contribute to it's rupture, the natural history of the illness, it's classification, association with other heart disease as well as diagnosis and treatment. PMID- 1417356 TI - [Doppler echocardiography assessment of tricuspid valve prosthesis with normal function and with dysfunction due to obstruction]. AB - In order to know the normal ranges of the maximum velocity and the pressure half time between normal functioning tricuspid prostheses and malfunctioning tricuspid prostheses due to obstruction, we studied 25 patients with tricuspid prostheses (11 mechanical and 14 biological); they were divided in 2 groups: group I: 14 patients without clinical evidence of malfunction and; group II: 11 patients with malfunction due to obstruction confirmed by catheterization, surgery and/or necropsy. The peak gradient was estimated by the modified Bernoulli equation and the prosthetic valve area by the pressure halftime method. RESULTS: the mean peak velocity in group I was 147 +/- 18 cm/sec versus 165 +/- 16 cm/sec (p NS) in group II. The mean pressure half-time in group I was 124 +/- 20 msec versus 355 +/- 48 msec (p less than 0.001) in group II. CONCLUSIONS: 1. A pressure half-time greater than 200 msec is very suggestive of malfunction due to obstruction (p less than 0.001). 2. There are normo-functioning tricuspid prostheses with prolonged pressure half-time, and the values that divides these groups from those with malfunction is small: 199 and 244 msec, that is why we suggest that every patient has to have his her own echocardiographic control in the immediate postoperative period. PMID- 1417357 TI - [Recessive autosomal inheritance in Marfan syndrome]. AB - Three brothers 9, 12, and 14 years of age were studied. The three of them fulfilled the diagnostic criteria of Marfan Syndrome that was made based on physical and ophthalmologic examination, these criteria included musculoskeletal abnormalities, subluxation of lens, myopia and aortic aneurysm. The three siblings died due to complications of the aortic aneurysm, which had an early onset as well as the other clinical manifestations of the disease. They were 2 brothers and one sister. There was neither mental or psychomotor retardation, nor metabolic disease in any of the patients. Family history did not show any clinical manifestation of the disease in parents or grandparents. We propose that the hereditary pattern is recessive autosomic instead of dominant autosomic given the features of these cases and their history. PMID- 1417358 TI - [The takeoff of cardiology at the meeting of 2 worlds]. PMID- 1417359 TI - [Physiologic features of the endothelium]. PMID- 1417360 TI - Influence of extracellular calcium on the actions of guanidine at the rat neuromuscular junction. AB - Guanidine has been shown to potentiate neurotransmission at the skeletal neuromuscular junction. The present study was undertaken to evaluate whether reductions in extracellular calcium affect the action of guanidine on the reversal of neuromuscular blockade induced by dibekacin and d-tubocurarine in the rat phrenic-hemidiaphragm preparation. Guanidine reversed the blocking effect of d-tubocurarine, the maximal effect occurring with 3 mM at 15 min. This reversal effect of guanidine was potentiated when the extracellular calcium concentration was reduced from 2.5 mM to 1 mM and 0.3 mM. Guanidine was also effective in reversing the neuromuscular depression caused by dibekacin. In this case, it was more potent than in the d-tubocurarine-treated preparations. The maximal effect was observed with 3 mM after 15 min of exposure. When the extracellular calcium concentration was reduced from 2.5 mM to 1 mM, a potentiation of guanidine effects was observed. In this situation, the maximal effect of guanidine was observed with only 0.7 mM. However, further reductions of extracellular calcium (0.3 mM) did not show further increases. The present results show that guanidine reverses the blockade induced by dibekacin and d-tubocurarine, being more potent against the former drug. This suggests that guanidine may be useful in relieving the blockade due to a restriction of calcium entry. Its effects were potentiated when the extracellular calcium concentration was lowered to 1 mM and, in d tubocurarine-treated muscles, to 0.3 mM. Thus, the effects of guanidine are calcium-dependent but only in a certain concentration range. PMID- 1417361 TI - Effects of bifemelane hydrochloride on loss of N-methyl-D-aspartate receptor and muscarinic cholinergic receptor binding in the gerbil hippocampus after transient ischemia. AB - The effects of bifemelane hydrochloride on changes of N-methyl-D-aspartate receptors and muscarinic cholinergic receptors were examined in the gerbil hippocampus after transient ischemia with radioactive-specific ligands. There were marked reductions in both these receptors in the gerbil hippocampus 14 days after transient ischemia, without changes in the respective affinities. Post ischemia bifemelane treatment almost completely prevented the ischemia-induced decreases in the numbers of these receptors, and had no effect in sham-operated controls. The results of the present study suggest that this drug prevents postsynaptic dysfunction induced by transient ischemia, and may be useful in the therapy of both the chronic and the acute stage of cerebrovascular disease. PMID- 1417362 TI - Influence of long-term lithium treatment on 5-hydroxytryptamine-mediated stimulation of adenylate cyclase in guinea-pig hippocampus. AB - The effects of long-term lithium treatment on the 5-hydroxytryptamine-mediated stimulation of adenylate cyclase activity in guinea-pig hippocampal membranes were examined. The stimulatory effect of 5-hydroxytryptamine on adenylate cyclase activity was guanine nucleotide-dependent and additive to those of dopamine, isoproterenol, norepinephrine, epinephrine and histamine. In contrast, the adenylate cyclase activity stimulated by 10 microM of 5-hydroxytryptamine plus 10 microM of 8-OH-DPAT was quite equal to that stimulated by 10 microM of 5 hydroxytryptamine alone. Oral administration of lithium for 3 weeks reduced, slightly but significantly, the concentration-response curve to 5 hydroxytryptamine but did not alter that to 8-OH-DPAT. Inhibition of the forskolin-stimulated adenylate cyclase activity by 5-hydroxytryptamine or 8-OH DPAT was shown to be unaltered after lithium treatment. The implications of these results are discussed with reference to previously reported data using hippocampal membranes prepared from rats. PMID- 1417363 TI - Reduction by carbachol of ventricular conduction impairments induced by various class I antiarrhythmic drugs in anesthetized dogs. AB - A common property of all Class I antiarrhythmic agents is the inhibition of the fast inward current INa. Consequently, ventricular conduction velocities are impaired and reentrant phenomena are counteracted. Unfortunately, these conductive pathway disturbances may also induce proarrhythmic effects and reduce cardiac contractility. Recent evidence indicates that a cholinergic agonist, carbachol, is able to correct in vitro both the duration of the action potential and the partial depolarization induced by lidocaine and quinidine in rabbit atria. In the present study, we demonstrated that i.v. carbachol is also a powerful agent in vivo for correcting conductive disturbances previously induced by four different Class I antiarrhythmic agents. The electrophysiological and hemodynamic parameters of ten groups of atropinized-anesthetized dogs, including six animals per group, were investigated. QRS duration, HV and V-St intervals were selected as in vivo indexes of ventricular conduction. Quinidine, procainamide, cibenzoline and flecainide were selected as representative agents of Class Ia and Ic antiarrhythmic drugs. In all treated groups, carbachol (1 mg/kg) was able to correct the indexes of ventricular conduction previously impaired by the antiarrhythmic drug used. PMID- 1417364 TI - Effects of chronic administration of lisuride hydrogen maleate on aromatic amine and metabolite levels in the gerbil brain following bilateral common carotid ligation. AB - Cerebral monoaminergic neurotransmitters and their metabolites show various concentration changes in gerbils following bilateral carotid ligation. The present study evaluated the effect of chronic administrations of lisuride hydrogen maleate (lisuride) on these changes. Lisuride (0.01 mg/kg or 0.05 mg/kg) or vehicle was intraperitoneally administered to gerbils for 14 consecutive days before the induction of a 30 min ischemia by bilateral carotid ligation. Animals were sacrified immediately and the levels of dopamine, DOPAC, homovanillic acid, noradrenaline, serotonin and 5-hydroxyindoleacetic acid determined by HPLC in the striatum, cortex, hippocampus and diencephalon/midbrain. Lisuride itself had no effect on any compound determined in any region. In the carotid-ligated gerbil brain, however, lisuride corrected the reduction of dopamine in the striatum, normalized or reduced increases in the (DOPAC+homovanillic acid)/dopamine ratio in the striatum, hippocampus and diencephalon/midbrain, and increased the levels of serotonin in all four regions. The present study, together with previous reports, indicate that lisuride may interfere with ischemia-induced cerebrovascular disturbances and, in such a way, improve some pathological sequelae of cerebrovascular disease. PMID- 1417365 TI - Vasodilatory activity of etozoline in rat and guinea-pig isolated aorta: study of the mechanism of action. AB - In isolated rings of guinea-pig aorta not responding to acetylcholine, the diuretic etozoline did not influence basal vascular tone but inhibited noradrenaline- and histamine-induced contractions. The inhibition was evident at concentrations of the diuretic (10 microM-1 mM) suitable to inhibit, in a competitive manner, the contractions evoked by a K+ channel blocker, tetraethylammonium, in the same preparation (Dorigo et al., 1989, 1990). In isolated rings of guinea-pig aorta, etozoline, at very low concentrations (1 nM 0.1 microM), inhibited also serotinin-induced contractions. The contractile effect of serotonin was abolished by nifedipine associated with 2-nitro-4 carboxyphenyl N,N-diphenyl-carbamate (an inhibitor of phospholipase C) or with etozoline, thus suggesting that the diuretic, besides inhibiting extracellular Ca++ uptake, also prevents intracellular Ca++ mobilization mediated by inositol triphosphate. In isolated rings of rat aorta responding to acetylcholine, etozoline did not influence basal vascular tone either in the absence or in the presence of superoxide-dismutase. In the same preparation, the diuretic inhibited vascular contractions induced by the three spasmogenic agents used, i.e. noradrenaline, histamine and serotonin. This inhibition occurred at concentrations of etozoline ranging from 10 microM to 1 mM and was uninfluenced by indomethacin (10 microMs). In isolated rings of rat aorta, the contractile effect of noradrenaline was not influenced by the addition of either 100 microM pyrogallol, or 10 microM methylene blue or 100 U/ml superoxide-dismutase, while the contractile responses to histamine and to serotonin were potentiated by pyrogallol and by methylene blue and reduced by superoxide-dismutase. This indicates that, in rat aorta, noradrenaline evokes only a direct contractile response, whereas both serotonin and histamine have a double effect: direct contraction of vascular smooth muscle and release of a relaxing factor from the endothelium. The inhibitory activity of etozoline towards serotonin- and histamine-induced contractions was reduced by pyrogallol and by methylene blue, whereas it was potentiated by superoxide-dismutase. The ability of etozoline to reverse the noradrenaline-induced contraction was unaffected by pyrogallol, methylene blue or superoxide-dismutase. These results emphasize the spasmolytic activity of etozoline, which seems to involve only the muscular component of rat and guinea-pig aorta. PMID- 1417366 TI - St-93 hyperglycemia in Wistar rats. AB - The alpha 2-adrenoceptor agonist St-93 was evaluated for its effect on blood glucose levels in Wistar rats. A dose-dependent increase in blood glucose was observed in rats after intraperitoneal administration of St-93. The hyperglycemic effect of St-93 was not altered by prazosin and propranolol, whereas idazoxan significantly inhibited this effect. Pretreatment with reserpine did not affect the hyperglycemic effect of St-93. There was no significant increase in the blood glucose values with St-93 in streptozotocin-diabetic rats. It may be concluded that the hyperglycemia induced by St-93 is mediated through alpha 2 adrenoceptors, possibly located on pancreatic beta-cells. PMID- 1417367 TI - Activation of capsaicin-sensitive primary afferents in the rat urinary bladder by compound 48/80: a direct action on sensory nerves? AB - We have assessed the ability of compound 48/80, a mast cell degranulating agent, to activate the sensory and efferent function of capsaicin-sensitive primary afferents in the rat urinary bladder. Compound 48/80 produced a calcium-dependent release of calcitonin gene-related peptide-like immunoreactivity from the superfused rat urinary bladder. This effect was prevented by in vitro capsaicin desensitization, but was not affected by indomethacin, methysergide, ondansetron, chlorpheniramine or cimetidine, nor by systemic pretreatment with compound 48/80 at a dose regimen which prevented lethality produced by intravenous administration of it in anesthetized rats. Compound 48/80 also produced a contraction of the rat isolated bladder which was not reduced by methysergide, indomethacin or in vitro capsaicin desensitization. In vivo, topical application of compound 48/80 on the serosal surface of the rat urinary bladder activated a series of high amplitude rhythmic bladder contractions which were hexamethonium sensitive (micturition reflex). This effect was prevented by systemic capsaicin desensitization while it was unchanged by chlorpheniramine, methysergide, indomethacin or ondansetron. Administered intravenously, compound 48/80 produced a plasma protein extravasation (Evans blue leakage technique) in the rat urinary bladder which was abolished by systemic capsaicin pretreatment or chlorpheniramine while it was unaffected by methysergide or indomethacin. The present findings provide direct neurochemical evidence that compound 48/80 activates the peripheral endings of capsaicin-sensitive primary afferent neurons, leading to a stimulation of their sensory and efferent functions in the rat urinary bladder. The possibility of a direct action of compound 48/80 in producing excitation of capsaicin-sensitive sensory nerves should be considered. PMID- 1417368 TI - The relative importance of focusing on elevations of systolic vs diastolic blood pressure. A definitive answer at last. PMID- 1417369 TI - Nasal carriage of Staphylococcus aureus and intravenous catheter phlebitis and sepsis. PMID- 1417370 TI - Advance directives and surrogate laws. Ethical instruments or moral cop-out? PMID- 1417371 TI - Inferior vena cava filters. Indications, safety, effectiveness. AB - BACKGROUND: Preventing pulmonary embolization by interrupting vena caval flow has been attempted since 1893. Inferior vena cava (IVC) filters have been available for 20 years, and currently there are five filters commercially available in the United States (Greenfield filter, Titanium Greenfield filter, Simon-Nitinol filter, Bird's Nest filter, and LGM or Vena Tech filter) and two other filters under development (Amplatz filter and Gunther filter). Although these devices are widely used, their clinical utility and safety have not been completely evaluated. Controlled clinical trials to determine the clinical role for IVC filters have not been attempted, but numerous case series describing the outcomes of the seven current filters have been published. We have systematically reviewed these studies to clarify what is known about the indications, safety, and effectiveness of IVC filters. METHODS: Using the MEDLINE database, all English language publications since 1970 that included follow-up clinical information after filter insertion were reviewed and eight methodologic guidelines were employed to assess the scientific quality of the clinical information. RESULTS: Twenty-four case series were reviewed: 16 concerned the Greenfield filter (1632 patients), and eight dealt with newer designs (925 patients). Commonly noted methodologic problems included failure to report the initial extent of thromboembolic disease, incomplete description of the patient assembly process, and incomplete and potentially biased outcome assessment. Recurrent clinical pulmonary embolism was rare after filter placement, and only eight deaths from pulmonary embolism were reported. Filter complications were common but rarely life threatening; four (0.16%) deaths from filter complications were noted among the reviewed studies. Thrombotic complications following filter placement included insertion-site deep vein thrombosis and IVC obstruction. These events were rare, but they occurred with all filter types. CONCLUSIONS: Inferior vena cava filters appear to be effective in preventing recurrent pulmonary embolism. Despite the large published experience with IVC filters, many questions remain about their indications, safety, and effectiveness. Anticoagulant therapy, if not contraindicated, should be used in conjunction with filters. While there is no ideal filter, some situations call for specific filters. Filter selection and insertion require experience, modern angiographic technique, and collaboration between clinicians caring for patients and the interventional radiologists or surgeons inserting the device. PMID- 1417372 TI - Cost-conscious prescribing of nonsteroidal anti-inflammatory drugs for adults with arthritis. A review and suggestions. AB - Salicylates and nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of painful disorders. This article reviews the efficacy, side effects, and costs of these agents and proposes a practical approach to using them in a cost-effective manner. Although there may be some differences in efficacy among available drugs, these do not appear sufficient to justify using the more expensive agents in most cases. Adverse effects, especially gastrointestinal (GI), add to the cost of using these drugs. Aspirin and all nonsalicylate NSAIDs share a risk of causing gastric ulcer, upper GI bleeding, and GI perforation. Prostaglandin inhibition by these agents may lead to reduced glomerular filtration rate and renal failure. There may be modest differences in GI and renal risks with the different agents, but these are minimal. Prophylaxis against gastric ulceration with anti-ulcer drugs has been recommended, and one agent, misoprostol, is approved for use in the United States for this purpose. Whether use of prophylaxis will increase or decrease the costs associated with NSAID therapy remains to be determined. Nonacetylated salicylates may cause less GI adverse effects and may be somewhat "renal sparing." Strategies that would reduce the cost of care for painful musculoskeletal disorders without compromising quality of care include using acetaminophen instead of an NSAID for noninflammatory disorders, trying nonacetylated salicylates as less expensive and safer alternatives to NSAIDs, using one agent at a time, allowing sufficient time to evaluate the therapeutic effect before changing agents, returning to the least expensive and/or safest drug if a trial of several in succession fails to find one that is clearly better, and reserving prophylactic use of antiulcer agents for patients who are at especially high risk and for whom anti-inflammatory effects are clearly needed. PMID- 1417373 TI - Pneumocystis prophylaxis and survival in patients with advanced human immunodeficiency virus infection treated with zidovudine. The Zidovudine Epidemiology Group. AB - BACKGROUND: Pneumocystis carinii pneumonia (PCP) is a major cause of morbidity and mortality in persons with advanced human immunodeficiency virus (HIV) infection. We assessed the impact of prophylaxis for PCP on survival in patients with advanced HIV disease who were treated with zidovudine. METHODS: A cohort of 1048 patients with prior PCP (N = 437), another acquired immunodeficiency syndrome-defining diagnosis (N = 168) or acquired immunodeficiency syndrome related complex (N = 443) and with less than 0.250 x 10(9)/L CD4 cells initiated zidovudine treatment between April 1987 and April 1988. They were then followed up for 24 months. Morbidity and mortality outcomes were assessed every 2 months. A time-dependent, Cox proportional hazards model was used to identify factors associated with new episodes of PCP and with survival. RESULTS: Three hundred thirty-six patients (32%) developed PCP after beginning treatment with zidovudine, with a 24-month actuarial rate of 41%. Patients with prior PCP were more likely to develop PCP during follow up (40%) than those without a history of PCP at entry (27% with PCP at follow-up). Other factors associated with developing PCP were baseline acquired immunodeficiency syndrome vs acquired immunodeficiency syndrome-related complex, and dose interruptions of zidovudine. Thirty-six (17%) of 210 patients who received trimethoprim-sulfamethoxazole prophylaxis developed PCP vs 299 (36%) of 838 who never received trimethoprim sulfamethoxazole (odds ratio, 0.48). One hundred seven (22%) of 483 patients who ever received aerosol pentamidine prophylaxis developed PCP vs 228 (40%) of 565 who did not receive aerosol pentamidine (odds ratio, 0.55). In a time-dependent Cox proportional hazards analysis, trimethoprim-sulfamethoxazole (relative hazard, 0.21; 95% confidence interval [CI], 0.11 to 0.4) and aerosol pentamidine prophylaxis (relative hazard, 0.25; 95% CI, 0.16 to 0.39) were associated with decreased risk of PCP. Pneumocystis carinii pneumonia during follow-up was strongly associated with death when controlling for other factors (odds ratio, 1.8). For all patients, aerosol pentamidine prophylaxis was associated with a reduced risk of death during follow-up (relative hazard, 0.59; 95% CI, 0.44 to 0.78), while trimethoprim-sulfamethoxazole showed a weaker association (relative hazard, 0.74; 95% CI, 0.54 to 1.1). However, there was a significantly reduced risk of death overall for patients who consistently used trimethoprim sulfamethoxazole (relative hazard, 0.55; 95% CI, 0.35 to 0.88) or aerosol pentamidine (relative hazard, 0.57; 95% CI, 0.42 to 0.77) and this was most pronounced in patients with a baseline history of PCP. DISCUSSION AND CONCLUSIONS: Pneumocystis carinii pneumonia was common in advanced HIV infection treated with zidovudine. Prophylaxis with trimethoprim-sulfamethoxazole and aerosol pentamidine both were associated with a decreased likelihood of PCP, and consistent use of each was associated with improved survival. Prophylaxis for PCP is associated with prolonged survival for patients with advanced HIV disease. PMID- 1417374 TI - Stroke complicating acute myocardial infarction. A meta-analysis of risk modification by anticoagulation and thrombolytic therapy. AB - BACKGROUND: The objective of this meta-analysis was to examine the impact of systemic anticoagulation and thrombolysis on the total incidence of stroke following myocardial infarction. Additionally, we sought to compare the relative risk of stroke with different thrombolytic agents. METHODS: A computerized and manual literature search for controlled clinical trials of anticoagulants and thrombolytic agents in myocardial infarction reporting on total strokes in treated and control patients was used. Pooling was performed by calculating the Mantel-Haenszel odds ratio and 95% confidence interval (CI). RESULTS: The Mantel Haenszel pooled odds ratio for anticoagulation trials was 0.46 (95% CI, 0.30 to 0.64), suggesting a benefit of anticoagulant therapy. However, a statistically significant degree of variability (heterogeneity) was present among study results. The odds ratios for all thrombolytic trials, tissue plasminogen activator, and streptokinase trials, respectively, were 1.08 (95% CI, 0.87 to 1.35), 1.28 (95% CI, 0.76 to 2.17), and 1.02 (95% CI, 0.80 to 1.30), suggesting no overall excess of stroke with thrombolysis. The pooled odds ratio for three studies directly comparing streptokinase and tissue plasminogen activator was 0.73 (95% CI, 0.61 to 0.86), suggesting an excess of stroke for patients treated with tissue plasminogen activator in comparison with streptokinase-treated patients. CONCLUSIONS: The available data may support a role for anticoagulants in reducing the incidence of stroke after myocardial infarction, but the heterogeneity among the trials makes interpretation of this effect difficult. Although the available data do not indicate an increase in stroke with thrombolysis, a direct comparison of tissue plasminogen activator and streptokinase reveals an excess of strokes with tissue plasminogen activator. PMID- 1417375 TI - A national survey of the home visiting practice and attitudes of family physicians and internists. AB - BACKGROUND: Over the past decade, while physician home visiting has continued to decline, the home care industry has been experiencing dramatic growth. In response, several major physician organizations have been encouraging increased physician education and involvement in home care and urging related health policy changes. This study provides the first in-depth, nationally representative descriptive data on the current home visiting practice and related attitudes of physicians. METHODS: Data were gathered through a structured 15-minute telephone survey, consisting of 141 items covering physician's general practice, personal home visiting practice, interaction with other home care providers, and attitudes regarding home care issues. Subjects were a nationally representative, randomly selected sample of 2200 family practice physicians (FPs) and internal medicine physicians (IMs) currently in active practice with at least 10 hours per week of professional time spent in ambulatory care. RESULTS: Sixty-five percent of eligible participants completed the survey. Of all physicians surveyed, 65% of FPs and 44% of IMs reported that they may make house calls (P less than .001). Mean number of visits per year was 21.2 (median, 10) for FPs, and it was 15.7 (median, 6) for IMs. Physicians in rural practice were more likely to make home visits (P less than .001). Physician attitudes related to home care reflect a strong dissatisfaction with reimbursement, but positive opinions about the use of other home care professionals and the importance of home visits for selected patients. Logistic regression analysis comparing home-visiting physicians with non-visiting physicians allowed for prediction of the correct classification 73% of the time, and it revealed six variables that were significant predictors of home visiting. The strongest of these predictors were the physician's positive attitude regarding the importance of home visits for selected patients and his or her perception of having time available for home visits. Other significant variables predictive of home visiting were family practice specialty, rural location of practice, greater numbers of referrals to home care agencies, and, interestingly, dissatisfaction with reimbursement. CONCLUSIONS: Although the great majority (over 75%) of FPs and IMs still regard the physician home visit as important for the care of selected patients, only about half report making one or more home visits within a 12-month period. Family physicians generally report a greater involvement in home care than do IMs. Physician reimbursement for home visits is perceived to be inadequate, and almost half (45%) indicate that they would do more home visits if reimbursement were increased. Most physicians (over 80%) have the opinion that home care agencies should be used more. PMID- 1417376 TI - Asthma management preceding an emergency department visit. AB - BACKGROUND: The burden of illness from asthma in North America has not decreased despite advancements in understanding disease pathogenesis and improved pharmacotherapeutics. This study examined the adequacy of preventive measures applied to asthma. METHODS: Using a standardized self-administered questionnaire, 111 consecutive patients presenting to the emergency department because of asthma were surveyed about their "usual" level of disability from asthma, usual medications, self-management plans to deal with an asthma attack, and environmental control measures. RESULTS: Twenty-five percent of subjects suffered sleep disturbance more than 15 days per month, had work/school attendance affected more than 14 days per year, and previously visited an emergency department twice in the past year. Thirty-seven percent had no effective plans to deal with an attack and another 32% had plans that were never discussed with a physician. Although 78% reported that cigarette smoke aggravated their asthma, one third of these were exposed at home. CONCLUSIONS: For a significant proportion of adults requiring emergency health services for asthma, preexisting management was poor by current standards. We recommend that patients be screened by emergency physicians and those with identifiable inadequacies in usual care be referred to physicians with expertise in asthma management. PMID- 1417377 TI - Low survival rate after cardiopulmonary resuscitation in a county hospital. AB - BACKGROUND: The standard of practice in hospitals in the United States is to perform cardiopulmonary resuscitation on all patients who suffer a cardiac arrest unless a specific order has been written to the contrary. In recent decades, however, data showing a low rate of survival to discharge under certain conditions have accumulated, leading some to question this policy. The objective of this study was to examine variables predictive of patient survival following cardiopulmonary resuscitation using standardized methods of measuring severity of illness. METHODS: All patients were identified who underwent cardiopulmonary resuscitation on the medicine service at Los Angeles County (California) Hospital from August 15, 1990, to February 15, 1991. Severity of illness was evaluated by examining diagnosis, Acute Physiology and Chronic Health Evaluation II score, and organ system failure. Cases were followed up prospectively until death or hospital discharge, and data concerning post-arrest mental status, utilization of resources, and disposition were gathered. RESULTS: Of the 131 patients identified, 22 patients (16.8%) survived for 24 hours but died before discharge; only four patients (3.1%) survived to discharge. CONCLUSIONS: This study suggests that in some settings (eg, institutions that are for sick patients under conditions where monitoring is limited because of scarcity of resources), survival after full cardiopulmonary arrest may be even lower than previously documented. PMID- 1417378 TI - Travel and ciguatera fish poisoning. AB - BACKGROUND: Ciguatera fish poisoning is a distinctive clinical syndrome associated with the consumption of contaminated marine fish. It is endemic in many popular travel destinations, including the Caribbean and Pacific Islands, where travelers are at risk. METHODS: Clinical review of 23 patients (60% were travelers) with ciguatera fish poisoning in whom consultation was provided between 1987 and 1990. RESULTS: Seven patients acquired ciguatera fish poisoning during international travel to the following destinations: Bahamas (n = 4), Dominican Republic (n = 1), British Virgin Islands (n = 1), and United States (n = 1). Suspected fish included grouper, red snapper, and amberjack. Two patients required emergency care, and four patients developed chronic symptoms. Severity was associated with chronicity, duration of peak symptoms, and worsening of symptoms with sexual activity. Chronicity was associated with severity, long latency period, and duration of peak symptoms. The three patients with complete resolution were scuba divers. Amitriptyline was the drug most often providing benefit for chronic symptoms. CONCLUSIONS: Ciguatera fish poisoning is a health risk to travelers to endemic regions, and their risk likely equals that of indigenous population groups. Barracuda should never be eaten, and travelers should exercise caution when considering other fish dishes, notably, grouper and red snapper. PMID- 1417379 TI - Hyperthyroidism as a cause of atrial fibrillation in long-term care. AB - BACKGROUND: We measured sensitive thyrotropin-stimulating hormone (sTSH) in 50 consecutive nursing home patients (39 men) with atrial fibrillation to determine the frequency of hyperthyroidism. METHODS: Patients were identified in a long term care facility by an electrocardiogram demonstrating atrial fibrillation. The sensitive thyrotropin-stimulating hormone assay had a detection limit of less than or equal to 0.02 mU/L (normal range, 0.46 to 3.60 mU/L). RESULTS: No subject had a suppressed sensitive thyrotropin-stimulating hormone. CONCLUSIONS: Hyperthyroidism is not a common cause of atrial fibrillation in male nursing home residents. PMID- 1417381 TI - Iatrogenic complications in high-risk, elderly patients. AB - BACKGROUND: This study explores the quality improvement potential of reviewing care for long-stay, elderly medicine service patients hospitalized for congestive heart failure, acute myocardial infarction, or pneumonia at a large Midwestern teaching hospital. METHODS: Medical records were reviewed for 120 patients aged 65 years or older who were discharged between January 1987 and June 1989, with hospital stays of 15 days or longer. Patients' severity of illness on admission was rated using the Medicare Mortality Predictor System; process quality of care was rated using a structured implicit review form for judging several dimensions of clinical assessment and decision making. Serious complications were coded by etiology and type and judged as possibly or probably preventable. Logistic regression was used to identify risk factors for iatrogenic events; multiple regression was used to assess potential outcome bias in ratings of overall quality of care. RESULTS: Of 120 medical records reviewed, 70 (58.3%) suffered at least one iatrogenic complication. Forty-three patients (35.8%) suffered an iatrogenic complication rated as potentially preventable. Significant predictors of all iatrogenic complications were quality ratings of initial physician assessment, patients' inability to walk unassisted, and low Glasgow Coma Score. For potentially preventable complications, quality ratings for physician documentation of functional status were also significant. Ratings for overall quality of care were not significantly influenced by the mere presence of death or complications. CONCLUSIONS: Iatrogenic complications are likely to be an extremely common experience for elderly medicine service patients with long lengths of stay. A significant portion of these complications may be potentially preventable with closer attention to initial assessment and documentation of patients' functional status. PMID- 1417380 TI - Transdermal clonidine reduced some withdrawal symptoms but did not increase smoking cessation. AB - BACKGROUND: Clonidine may be useful in controlling tobacco withdrawal and in facilitating smoking cessation. This study was developed to test the efficacy of transdermal clonidine in promoting smoking cessation. METHODS: We conducted a five-center, double-blind, placebo-controlled, randomized controlled trial of transdermal clonidine in conjunction with a minimal behavioral intervention for smoking cessation. The intervention was based on the American Lung Association's Freedom From Smoking program. Self report of not smoking was validated with exhaled air carbon monoxide of less than 8 ppm and salivary cotinine of less than 20 ng/mL. Transdermal clonidine therapy began 1 week before the target quit date: 0.1 mg/24 h for the first 4 days increasing to 0.2 mg/24 h for the next 3 days, if the lower dose was tolerated. The highest tolerated dose was then continued for 6 weeks after target quit day. Withdrawal symptoms were measured daily for the first 7 days after target quit day. RESULTS: A total of 213 patients were enrolled (106 active drug and 107 placebo). During the study, 15.5% of patients had drug therapy discontinued due to adverse effects, 24.5% (26/106) taking active drug vs 8.4% (9/107) receiving placebo. There was a significant reduction in anxiety score from 3.0 to 2.4 (placebo vs active) and irritability score from 2.2 to 1.7 (placebo vs active) during the first week after cessation. There was no reduction in other withdrawal symptoms. The overall 12-week abstinence rate was 33.0% (35/106) in the active drug group vs 34.5% (37/107) in the placebo group (not significant). CONCLUSION: This study demonstrated some reduction in early withdrawal symptoms with the use of a clonidine transdermal patch, but no increase in cessation rate, 6 weeks after medication had been discontinued. PMID- 1417382 TI - Clinical prognostic factors in lupus nephritis. The importance of hypertension and smoking. AB - BACKGROUND: Many previous studies of the influence of sociodemographic and clinical factors on the development of renal failure in patients with lupus nephritis have been based on selected subgroups of patients and have yielded conflicting results. We sought to determine the prognostic importance of patient demographic characteristics (age, gender, race, and socioeconomic status), smoking status, and hypertension in the development of end-stage renal disease (ESRD) among patients with lupus nephritis. METHODS: This retrospective cohort study followed an inception cohort of 160 adults with lupus nephritis. The outcome measure was the development of ESRD, defined as the institution of maintenance dialysis or measurement of a creatinine clearance of 10 mL/min or less. Life-table analysis was used to determine differences between patient subgroups in the time to development of ESRD. RESULTS: End-stage renal disease developed in 41 (26%) of 160 patients followed up for a median of 6.4 years. Hypertension and smoking status at the onset of nephritis were strongly associated with differences in the time to development of ESRD. The median time to ESRD among patients with moderate to severe hypertension (diastolic blood pressure, greater than or equal to 105 mm Hg) was 7 months, among patients with mild hypertension (diastolic blood pressure, 90 to 104 mm Hg) it was 146 months, and among normotensive patients it was greater than 273 months. The median time to ESRD among smokers was 145 months and among nonsmokers it was greater than 273 months. These effects persisted in multivariable analyses adjusting for differences among patients in age, gender, socioeconomic status, renal histology, and immunosuppressive treatment. The independent effects of hypertension and smoking resulted in shorter times to renal failure among patients who were both hypertensive and smoking, compared with nonsmoking hypertensive patients. The development of ESRD did not differ among patient demographic subgroups. CONCLUSION: Patient demographic characteristics had no detectable impact on the rate of progression to ESRD in this cohort. Hypertension and smoking appear to be important, potentially modifiable, factors influencing the prognosis of patients with lupus nephritis. PMID- 1417383 TI - A comparison of two-dimensional echocardiography vs carotid duplex scanning in older patients with cerebral ischemia. AB - BACKGROUND: To determine the relative value of two-dimensional (2D) echocardiography vs carotid duplex scanning and to devise an optimal, cost effective diagnostic approach for older patients with cerebral ischemia, 68 consecutive patients in sinus rhythm who suffered focal cerebral ischemia were studied. All patients underwent 2D echocardiography and carotid duplex scanning in addition to routine clinical evaluation. METHODS: Twenty-five of 68 patients had Q-wave myocardial infarction by electrocardiography; nine (36%) of these 25 had left ventricular mural thrombi demonstrated by 2D echocardiography. In contrast, none of 43 patients without Q-wave myocardial infarction had clinically unsuspected findings diagnosed by 2D echocardiography. Duplex scanning, however, identified significant, abnormal findings in the carotid artery ipsilateral to the involved cerebral hemisphere in 23 patients (34%). CONCLUSIONS: Thus, in older patients in sinus rhythm who suffer a cerebral ischemic event, carotid duplex scanning has a higher diagnostic yield than 2D echocardiography and appears to be a more cost-effective initial test. Our data suggest that in patients with carotid distribution cerebral ischemic events and no obvious cardiac source for emboli by history and physical examination, 2D echocardiography should be limited to those with evidence of Q-wave myocardial infarction by electrocardiography; such management should optimize diagnostic yield and cost effectiveness. PMID- 1417384 TI - Severity of hepatic encephalopathy before liver transplantation is associated with quality of life after transplantation. AB - BACKGROUND: Cirrhosis is associated with a chronic low-grade hepatic encephalopathy and disturbances in quality of life. This study investigated the extent to which severity of hepatic encephalopathy before orthotopic liver transplantation correlated with quality of life. METHODS: A battery of neuropsychological tests was administered to nonalcoholic patients to quantify severity of hepatic encephalopathy. The Sickness Impact Profile was administered before and after surgery to document quality of life across multiple health and psychosocial dimensions. RESULTS: There was substantial improvement from the pretransplant to the posttransplant periods across almost all dimensions of quality of life. Neuropsychological test scores explained up to 20% of the variance in magnitude of change from pre (before) to post (after) surgery. CONCLUSION: Severity of hepatic encephalopathy (particularly with respect to static ataxia and fine motor control) is associated with posttransplantation improvement in quality of life. PMID- 1417385 TI - A prospective study of Staphylococcus aureus nasal colonization and intravenous therapy-related phlebitis. AB - BACKGROUND: Intravenous (IV) therapy-associated phlebitis is common, but its causes are ill defined. Some cases may be related to bacterial colonization of the skin surrounding the IV catheter, especially by Staphylococcus aureus. This prospective study examined the association of phlebitis with anterior nares S aureus carriage, as well as with other potential risk factors. METHODS: Selected demographic and clinical data and a nares culture were collected from patients on designated wards by us and from the IV therapy team at the time of initial IV catheter placement. Patients were followed up for signs and symptoms of phlebitis for the duration of the initial catheter's use and for up to two additional IV placements. Potential risk factors were compared for patients who developed phlebitis and those who did not by the Cox multivariate proportional hazards model. RESULTS: During 10 weeks, 273 men with a total of 416 catheter placements had fully evaluable data. Phlebitis occurred during 13.7% of the catheter placements. Nasal cultures yielded S aureus from 14.3% of the patients, but none of the IV team nurses. Surprisingly, S aureus nasal colonization was related (at borderline statistical significance) to a reduction in phlebitis risk. Location of the patient on a surgical ward, the presence of infection at any site, and a larger-gauge catheter were each significant independent risk factors for phlebitis. The highest risk of phlebitis appeared to have been within 12 to 24 hours of catheter placement. CONCLUSIONS: The primary finding of this study was that nasal colonization with S aureus did not increase the risk of developing IV catheter-associated phlebitis. Our rate of IV catheter-associated phlebitis was similar to that in other studies, but the factors predisposing to phlebitis differed somewhat from those in previous studies. PMID- 1417387 TI - Orthostatic hypotension in ciguatera fish poisoning. AB - PURPOSE: The purpose of this study was to investigate the pathophysiology of persistent orthostatic hypotension in a patient with ciguatera fish poisoning. METHODS: A patient who became ill and who developed prolonged and symptomatic orthostatic hypotension with ciguatera fish poisoning after eating barracuda is described. Studies of autonomic function included measurements of plasma catecholamine levels in the supine and standing positions, and pressor responses to infusions of norepinephrine, atropine, and propranolol. RESULTS: Volume depletion was excluded as a cause for hypotension. Our patient showed low plasma catecholamine levels and marked pressor hypersensitivity to norepinephrine infusion. Hypotension and bradycardia were reversed by atropine infusion. The heart rate freed from autonomic influences, ie, after atropine plus propranolol infusion, was normal. CONCLUSIONS: In ciguatera fish poisoning, orthostatic hypotension appears to be a result of both parasympathetic excess and sympathetic failure. PMID- 1417386 TI - Relationship of general advance directive instructions to specific life sustaining treatment preferences in patients with serious illness. AB - OBJECTIVE: To determine whether brief general instructions in a typical proxy instruction advance directive (California Durable Power of Attorney for Health Care [DPAHC]) provide interpretable information about patient requests to limit life-saving treatments, and to determine whether patient treatment preferences are stable over time. DESIGN: Prospective structured interviews. SETTING: University of California, San Diego Medical Center and Veterans Affairs Medical Center, La Jolla. PATIENTS: One hundred four patients (from a randomly chosen sample of 185) with a 5-year life expectancy of no better than 50% as judged by their physicians. MAIN OUTCOME MEASURES: Patients completed the California DPAHC, a proxy-instruction advance directive, at entry and at 1 year. The patients also completed a questionnaire at entry, after 6 months, and after 1 year, indicating their preferences on a five-point Likert-format comparative rating scale for cardiopulmonary resuscitation, mechanical ventilation, artificial nutrition, and hospitalization for pneumonia. RESULTS: Sixty-eight percent of the subjects executed the DPAHC. Most patients wished treatments to be limited or withheld under certain conditions of reduced quality of life. Although general instructions noted on the DPAHC and preferences regarding specific procedures were stable over the course of a year, the advance directive's general instructions were often inconsistent with, and poor predictors of, specific procedure preferences. CONCLUSIONS: The brief general instruction component of the California DPAHC is not helpful in communicating patient wishes regarding specific life-saving procedures. PMID- 1417388 TI - The antiproteinuric effect of antihypertensive agents in diabetic nephropathy. PMID- 1417389 TI - Empiric treatment of acute Toxoplasma encephalitis in patients with acquired immunodeficiency syndrome. PMID- 1417390 TI - Standardization of heparin therapy improves efficacy. PMID- 1417392 TI - Isolated angiopathy of the central nervous system. PMID- 1417391 TI - Serum thyrotropin levels and adrenotoxicosis. PMID- 1417393 TI - Report on other drug use among persons previously reported to have received intravenous cimetidine. PMID- 1417394 TI - [Defined contusion marks caused by the knife handle]. AB - If in inflicting a stab wound the knife is vigorously pushed in up to the end of the blade, this does not only cause cutting of the tissue, but also a blunt traumatization. The resulting abrasions can correspond with the respective construction parts (handle, handguard, devices for fixing the open blade) as to position, shape and size, thus allowing conclusions as to the shape of the instrument used. Incomplete, one-sided marks of the handle suggest an oblique angled stab. The presence of a contusion mark shows that the blade penetrated completely, which makes it easier to draw conclusions as to the length of the blade from the depth of penetration. The reconstruction possibilities are demonstrated on the basis of three autopsies (homicide cases with different types of knives). PMID- 1417395 TI - [Uncovered bones on the Baltic Sea beach--human or animal?]. AB - Report of an unusual finding of bones on the shore of the Baltic Sea. Although the morphological findings appeared similar to a human foot skeleton, a quick identification as sea dog bone was possible. PMID- 1417396 TI - [Contamination in illegal amphetamine. Contaminants resulting from the synthesis of 3,4-(methylenedioxy)amphetamine (MDA) via condensation between nitroethane and piperonal]. AB - Some impurities of illegally synthesized 3.4-(methylenedioxy)amphetamine (MDA) are presented. These compounds were detected in laboratory glassware which had been used for the synthesis of MDA via phenyl nitropropene route. PMID- 1417397 TI - [Prostaglandin E in vaginal smears--a possibility for sperm detection in azoospermia]. AB - The identification of seminal traces is exceptionally difficult, if the semen of the assailant is azoospermic. The evident value of prostatic acid phosphatase (PAP) activity must be evaluated in such cases with caution. In a murder investigation of a 13 year old girl a positive PAP reaction was found in vaginal swabs and in her underpants. Spermatozoa could not be found. Using the gas chromatographic method, described by Douse (1985) the presence of prostaglandin E could be demonstrated in the swabs as well as in the crotch of the underpants. The offender was found to be a man with azoospermia, who admitted intercourse but with the consent of the victim. The E prostaglandins are mainly synthesized in the vesiculae seminal and seen to be specific for semen. Swabs taken from mouth and rectum showed negative reactions for prostaglandins in this case. Prostaglandins could never be detected in vaginal swabs taken at least 7 days after intercourse. Conversely Douse could detect prostaglandins in swabs up to 58 hours after intercourse. Apparently the prostaglandin detection by Douse provides a suitable alternative besides to the quantitative and immunological PAP detection or the immunological detection of the protein p 30. PMID- 1417398 TI - [Unusual cases of self-asphyxiation]. AB - Based on the description of the findings of four cases of self-strangulation with multiple knotting of the strangling device examined by the authors general criminological and specific forensic criteria for differential diagnosis of suicide and commission of the offence by another person are discussed. Though multiple knotting of the strangling device, caught hair and parts of clothes and concomitant injuries may also be seen in cases of suicide, they primarily justify the suspicion that the death was caused by another person. If it is one of those rare cases of self-strangulation with multiple knotting, the presence of symptoms of congestion in the head area, which may occasionally be absent in other cases of strangulation, is necessary for pathophysiological reasons. PMID- 1417399 TI - [Coronary angioplasty of multivessel coronary diseases. Apropos of 1664 procedures. Immediate results and results following 6 months]. AB - Between 1980 and 1990, 1,664 coronary angioplasty procedures were performed in 1,307 patients (86.6% male) with multivessel disease. The average age was 57 +/- 3 years (range 29 to 83 years). There was a previous history of infarction in 40.1% of patients and 22.4% of the procedures were performed for unstable angina. Catheter and 58.2%, 1,220 double vessel and 444 triple vessel diseases. A total of 2,509 lesions were dilated (1.5 stenoses/patient). The primary success rate was 81.9% with 3.2% of infarcts and 3.5% emergency bypass procedures and a global mortality of 2%. The factors responsible for death in the acute and hospital phases were unstable angina, age > 70 years, and ejection fraction < 35%. Complete revascularisation was achieved in 14.3% of cases: the only predictive factor for complete revascularisation on multivariate analysis was double vessel disease. A 6 months clinical and angiographic control was obtained for 83.8% of controllable procedures (965 dilatations). The restenosis rate was 47.9%. Univariate analysis of the factors of restenosis identified clinical parameters (age > 58 years, triple vessel disease, diabetes and unstable angina), parameters related to the lesion (length of stenosis > 1 cm, percentage stenosis > 80%) and to the procedure (residual stenosis > 20%): 68.4% of patients with restenosis underwent repeat angioplasty with a significantly superior primary success rate 88.7% vs 81.9% of global successes (p < 0.001). With a 82% primary success rate with few major complications, coronary angioplasty is a safe and effective therapeutic alternative. The extent of the lesions and the presence of chronic occlusion are the main limitating factors of revascularisation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417400 TI - [Relative value of attenuation and negativation of systolic pulmonary venous flow in severe mitral insufficiency. Transesophageal echocardiographic study]. AB - The aim of this study was to analyse the velocity profile of the systolic fraction of the pulmonary venous flow (PVF) in mitral regurgitation (MR). Three velocity profiles were identified in left superior pulmonary vein. Inversion of the systolic fraction of the PVF was specific for angiographic grade 4 MR (specificity 97%, sensitivity 100%). On the other hand, a decrease in this wave is much less specific for mild MR and depends on severe factors such as left atrial pressure, size and ejection fraction and the lack of atrial systole (as in atrial fibrillation or atrioventricular block). Therefore, inversion of PVF has a good positive predictive value for severe MR, but the interpretation of attenuation of this wave should take into consideration not only the MR but also left atrial pressure and compliance. PMID- 1417401 TI - [Value of signal-averaged electrocardiogram in ventricular arrhythmia without apparent heart disease]. AB - Signal-averaged electrocardiography was performed in 132 subjects with various ventricular arrhythmias without clinically apparent heart disease and compared with the results obtained in a series of 45 normal subjects. The latter enabled definition of the following criteria of normality: QRS duration after averaging < 113 ms; Simson vector of the last 40 ms (RMS40) > or = 17 microV; low amplitude signal duration over 40 microV < 38 ms for a high pass bidirectional filter of 40 300 Hz. Complementary investigations (echo or angiography), performed in all cases, showed underlying abnormalities in 26 patients: 13 right ventricular dysplasias, 7 cardiomyopathies, 3 mitral valve prolapses and 3 minor congenital heart defects. These investigations were normal in the remaining 106 subjects. Of the 26 patients with cardiac disease, 15 had 3 criteria of positivity for late ventricular potentials, 6 had 2 criteria and the other 5 had no criteria of late ventricular potentials. Therefore, 81% of cases with cardiac disease had at least 2 diagnostic criteria of late ventricular potentials whereas only 4% of those without cardiac disease, and in the control group, had criteria of positivity (p < 0.001). Using these criteria, the predictive value of signal-averaged electrocardiography for the detection of underlying cardiac disease was good when 2 criteria are required for diagnosis of late ventricular potentials: sensitivity 81%, specificity 96%; predictive value of a positive test 78%, predictive value of a negative test 97%. Signal-averaged electrocardiography is therefore a good non-invasive method of diagnosing underlying cardiac disease in patients with ventricular arrhythmias without clinically apparent heart disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417402 TI - [Left intraventricular gradients measured by Doppler echocardiography at rest, during exercise and during isoproterenol test in hypertrophic cardiomyopathy]. AB - Doppler echocardiography has been shown to be an accurate method of assessing left ventricular outflow obstruction in hypertrophic cardiomyopathy (HCM). One of the characteristics of this pressure gradient is its variability and, therefore, we measured this parameter during dynamic exercise testing in 33 patients. The results were compared with those recorded during isoproterenol infusion, the reference stress test for patients with HCM. Submaximal exercise in the recumbent position is usually well tolerated and resulted in a 43% increase in heart rate and a 47% increase in pressure gradient. There was a significant correlation between resting and exercise outflow obstruction (r = 0.90; p = 0.001). Moreover, exercise echo revealed obstruction in 26% of patients without resting pressure gradients (latent obstruction). The interpretation of results obtained with isoproterenol infusion is more difficult: this test resulted in an important increase in the left ventricular pressure gradient (231%) and "revealed" obstruction in 84% of cases. Therefore, we believe that exercise is more physiological and better tolerated than isoproterenol stress infusion and should be adopted as the investigation of choice in HCM even without obstruction at rest. If it is not possible to perform the exercise or no outflow tract obstruction can be demonstrated, an isoproterenol infusion may be used but this is not always well tolerated and the results should be interpreted with caution. PMID- 1417403 TI - [Can solid state Holter monitoring replace endomyocardial biopsy in patients with heart transplantation?]. AB - Acute cardiac graft rejection after transplantation, the diagnosis of which is based on the findings of endomyocardial biopsy, is associated with a reduction in coronary reserve due to abnormalities of the microcirculation. But this reduction in coronary reserve cause silent myocardial ischaemia (SMI)? In order to assess the frequency of SMI and ventricular arrhythmias during rejection, 53 consecutive Holter recordings were performed in 32 patients (28 men, 4 women, average age 47 +/- 11 years) 11 months after transplantation and within 24 hours of endomyocardial biopsy. The recorder which was used (Monitor One TC) analysed the ST segment in 2 leads in real time: ST segment depression of more than 1 mm lasting over 40 ms, 0.08 s after the J point were considered to be diagnostic of myocardial ischaemia. Although the frequency of SMI is low and not specific for cardiac rejection, its duration was twice as long (80 mn vs 38 mn) in this condition. On the other hand, ventricular arrhythmias are common in cardiac rejection and correlated with its severity according to Billingham's classification (VES p = 0.045; doublets p = 0.035; non-sustained VT p = 0.006). PMID- 1417404 TI - [Percutaneous ablation of atrioventricular junction by radiofrequency current in resistant atrial arrhythmia. Results of a series of 24 patients]. AB - Catheter ablation of the atrioventricular junction may be proposed for the treatment of certain atrial arrhythmias resistant to antiarrhythmic therapy. One of the methods currently being evaluated uses radio-frequency energy which has certain advantages compared with direct current ablation because of the progressive and limited lesions it produces. This technique was used in 24 patients with atrial arrhythmias resistant to antiarrhythmic therapy. The radio frequency energy was delivered without general anaesthesia with HAT 100 and 200 (OSYPKA) generators in the unipolar mode (average 17.4 watts) for an average period of 22.3 +/- 8 seconds. The catheter (8F USCI suction catheter in the first 18 patients and a 7F Polaris Mansfield, deflectable catheter with a large distal electrode in the remainder) was positioned at the nodo-hisian junction at a point where the two distal electrodes recorded a large atrial deflection and the smallest possible hisian potential. The conduction defects induced during the acute phase generally remain stable in cases of complete atrioventricular block and tend to regress in cases of incomplete atrioventricular block despite initial control of atrioventricular conduction. During follow-up (21 +/- 16 months), 14 patients (58%) remained in complete atrioventricular block, 4 patients (17%) had controlled atrioventricular conduction with an acceptable ventricular rate with associated previously ineffective antiarrhythmic therapy. Radio-frequency ablation was a failure in 6 patients (25%). There were no haemodynamic, rhythmic or ischaemic complications during the acute phase or during follow-up. These results suggest radio-frequency energy is a seductive alternative to direct current ablation for percutaneous modification of atrioventricular conduction in patients with refractory atrial arrhythmias. However, simple modulation of atrioventricular conduction gives aleatory results due to the tendency to regression during follow-up. On the other hand, complete atrioventricular blocks created by radio-frequency energy are generally definitive and are associated with a junctional escape rhythm which is usually stable. PMID- 1417405 TI - [Left ventricular filling and left bundle branch block: an echocardiographic and radionuclide study]. AB - Left bundle branch block changes the activation and haemodynamics of the left ventricle. In order to evaluate its consequences on left ventricular filling, the duration of the isovolumic relaxation period, the velocities and the integrals of the rapid and slow filling waves were recorded by Doppler echocardiography and the ejection fraction, the peak filling rate and its time of apparition were measured by gamma angiocardiography in 18 patients aged 55 +/- 9 years and 18 control subjects aged 53 +/- 9 years. Left bundle branch block was associated with a prolonged isovolumic relaxation period (104 +/- 14 vs 88 +/- 11 ms) a delayed and reduced peak filling rate and an increased atrial filling velocity at a heart rate comparable to that of control subjects (69 +/- 9 vs 72 +/- 8 beats/mn). Despite these changes in left ventricular relaxation and filling and a reduced ejection fraction (55 +/- 7 vs 61 +/- 6%, p < 0.01) cardiac output was not significantly decreased in left bundle branch block (4.9 +/- 1 vs 5.2 +/- 0.9 l/mn). Therefore, left bundle branch block interferes with left ventricular filling and ejection fraction without decreasing the resting enddiastolic volume. PMID- 1417406 TI - [Thrombi of the right heart. Value of thrombolytic therapy in mobile thrombi]. AB - Seven patients with mobile right heart thrombi, 4 floating and 3 pediculated, were recensed between 1985 and 1990. Two patients were admitted for congestive cardiac failure (Group I) and 5 patients for pulmonary embolism (Group II). Both patients in Group I were treated with heparin without complications. In one case, the size of the thrombus decreased in 10 days whereas, in the second case, it disappeared within 8 days. In Group II, the first patient underwent successful thrombectomy. The other four patients were given thrombolytic therapy (UK = 2, rt PA = 2) associated with appropriate doses of heparin. In the two patients given UK (3M units the first day followed by 1.2 M units per day for 4 days) the thrombus disappeared in the first 48 hours of treatment. One patient had a recurrent pulmonary embolism after 2 hours' treatment; both patients had a fall in haemoglobin of 3 cg/ml at the second day. The second patient died at the 5th day. In the two patients treated by rt-PA (100 mg/7 hours) the thrombus disappeared within 4 hours of starting therapy. One patient had a probable recurrent pulmonary embolism. Both patients had a fall in haemoglobin of 3 cg/ml at the 2nd day of treatment. Right heart thrombi are rare (168 cases in the literature of which 111 were mobile). The prognosis seems to be related to echocardiographic appearances: mortality of mural thrombi is about 4% compared with 50% in mobile thrombi. Very mobile "worm-like" masses are therapeutic emergencies because of the risk of embolism (about 68%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417407 TI - [Diastolic function of the left ventricle in aortic valve stenosis. Doppler echocardiography]. AB - Doppler echocardiographic parameters of LV diastolic function (isovolumic relaxation time, E wave velocity, ratio of E/A wave velocities, mitral valve pressure half time) were compared to catheter data in 35 patients (average age 67 years) with pure or dominant aortic stenosis (mean gradient: 65 +/- 30 mmHg). The isovolumic relaxation time was prolonged in most patients (m = 103 +/- 23 ms) and seemed uninfluenced by any haemodynamic parameter. There was a positive correlation between pressure half time and ejection fraction (r = 0.41, p = 0.02) and a negative correlation with pulmonary capillary pressure (r = -0.61, p < 0.01). The E and E/A ratio were negatively correlated with the ejection fraction (r = -0.41 and -0.52) and positively correlated with pulmonary capillary pressure (r = 0.46 and 0.62). The Doppler parameters were independant of the patients' age, severity of stenosis and degree of left ventricular hypertrophy. Patients with normal pulmonary capillary pressure (< 15 mmHg, N = 19) had abnormal diastolic filling with low E wave velocities (71 +/- 28 cm/s) and E/A ratios (0.9 +/- 0.6) and prolonged half pressure times (96 +/- 37 ms). Conversely, patients with high pulmonary capillary pressures (> 15 mmHg, N = 16) had normal or high E wave velocities (107 +/- 31 cm/s) and E/A ratios (1.5 +/- 0.6) and normal or shortened isovolumic relaxation times (62 +/- 22 ms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417408 TI - [Proarrhythmic effects of antiarrhythmic drugs]. AB - The proarrhythmic effects of antiarrhythmic drugs are complications which have been described over several decades but the mechanisms (reentry, increased automaticity, ectopic faci, induced repetitive activity, vagal or adrenergic triggers) and the predisposing factors (underlying cardiac disease, previous severe arrhythmia, metabolic disorders, ischaemia, etc...) have only recently been identified. The appreciation of their true frequency poses problems of methodology (mode of recruitment, therapeutic converse proof), of definitions and depends to a great extent on the methods of detection used. Their severity cannot be denied and has been demonstrated both in experience of isolated cases and in recent prospective studies, the conclusions of which must be interpreted critically. Proarrhythmic effects may be observed at atrial (vagal or sympathetic arrhythmias, 1/1 flutter, acceleration of atrial fibrillation in preexcitation syndromes), junctional (artificial unidirectional block created by the antiarrhythmic drug which may be very effective at higher dosages: biphasic effect) or ventricular (aggravation of ventricular extrasystoles, torsades de pointe, ventricular tachycardia/fibrillation) levels. It is curious that no antiarrhythmic drug seems to be statistically less exposed to this type of complication which may result from phenomena of toxicity or idiosyncrasy. Given the potential gravity measures must be taken to prevent this complication, by observing simple rules (respect of contraindication, use of progressive dosage regimens, avoidance of loading doses, elimination of predisposing factors and abstention from dangerous therapeutic associations) and by carefully following up high risk patients. PMID- 1417409 TI - [Potential value of omega-3 polyunsaturated fatty acids in the prevention of atherosclerosis and cardiovascular diseases]. AB - Several epidemiological studies have shown decreased cardiovascular mortality and a lower incidence of coronary artery disease in subjects with high dietary intakes of Omega-3 polyunsaturated fatty acids. It has since been shown that Omega-3 fatty acids have a number of beneficial effects in the prevention of atherosclerosis in man: reduction of blood pressure, modifications of lipoprotein metabolism, modifications of haemostasis (increased bleeding time and reduced platelet aggregation), decreased plasma fibrinogen, modifications of the metabolism of arachidonic acid and its derivatives (decreased thromboxane and leukotriene synthesis, increased prostacyclin synthesis). Therefore, Omega-3 polyunsaturated fatty acids have several beneficial effects on the presumed mechanisms of atherogenesis and/or its complications: they could represent an original and seductive solution to the problem of prevention of cardiovascular disease. PMID- 1417410 TI - [Peripheral calcific embolism after percutaneous mitral valvuloplasty]. AB - The authors report a case of calcific embolization after percutaneous mitral valvuloplasty. The nature of the embolism was confirmed by anatomopathological examination after popliteal embolectomy. This complication would appear to be extremely rare but represents an additional risk in patients with calcific mitral stenosis. PMID- 1417411 TI - [Right intra-atrial extension of hydatid cyst mimicking cardiac thrombosis. Apropos of a case]. AB - The authors describe an unusual case of hydatid cyst inserted in the inferior vena cava and extending into the right atrium. The transoesoesophageal echocardiographic appearances were similar to those of a thrombus: the tumour was very mobile, echogenic, polylobular with a cord-like pedicle in the inferior vena cava. The pathological examination revealed a ruptured hydatid cyst. The mass and its insertion were not visible on CT scan or cavography. Transoesophageal echocardiography would therefore seem to be a very useful diagnostic method for tumours arising in the inferior vena cava and extending into the right atrium. PMID- 1417412 TI - [Cardiovascular manifestations of Cogan syndrome. Apropos of a case]. AB - The authors describe a case of Cogan's syndrome in a patient with ulcerative colitis complicated by several cardiovascular manifestations including bilateral coronary ostial stenosis, rapidly progressive aortic regurgitation and aneurysm of the thoracic aorta, thrombosis of the common iliac artery and pericardial symphysis. This rare form of inflammatory arteritis, the diagnosis of which is usually made on the finding of associated ocular and auditory involvement, is distinct from other types of angiitis by the predisposition to severe cardiovascular complications which influence the vital prognosis. The differential diagnosis with more common collagen diseases with cardiovascular complications is discussed. PMID- 1417413 TI - Nucleotide sequence of the rpoN (hno) gene region of Alcaligenes eutrophus: evidence for a conserved gene cluster. AB - The nucleotide sequence of the rpoN gene, formerly designated hno, and flanking DNA regions of the aerobic hydrogen bacterium Alcaligenes eutrophus has been determined; rpoN codes for the RNA polymerase sigma factor sigma 54 involved in nitrogen regulation and diverse physiological functions of gram-negative bacteria. In A. eutrophus hydrogen metabolism is under control of rpoN. The Tn5 Mob insertion in a previously isolated pleiotropic mutant was mapped within the rpoN gene. The derived amino acid sequence of the A. eutrophus RpoN protein shows extensive homology to the RpoN proteins of other organisms. Sequencing revealed four other open reading frames: one upstream (ORF280) and three downstream (ORF130, ORF99 and ORF greater than 54) of the rpoN gene. A similar arrangement of homologous ORFs is found in the rpoN regions of other bacteria and is indicative of a conserved gene cluster. PMID- 1417414 TI - The influence of congo red on the cell wall and (1----3)-beta-D-glucan microfibril biogenesis in Saccharomyces cerevisiae. AB - Congo red was applied to growing yeast cells and regenerating protoplasts in order to study its effects on wall biogenesis and cell morphogenesis. In the presence of the dye, the whole yeast cells grew and divided to form chains of connected cells showing aberrant wall structures on both sides of the septum. The wall-less protoplasts in solid medium with the dye exhibited an abnormal increase in volume, regeneration of aberrant cell walls and inability to carry out cytokinesis or protoplast reversion to cells. In liquid medium, the protoplasts synthesized glucan nets composed mainly of thin fibrils orientated at random, whereas normally, in the absence of dye, the nets consist of rather thick fibrils, 10 to 20 nm in width, assembled into broad ribbons. These fibrils are known to consist of triple 6/1 helical strands of (1----3)-beta-D-glucan aggregated laterally in crystalline packing. The thin fibrils (c. 4 to 8 nm wide) can contain only a few triple helical strands (c. 1.6 nm wide) and are supposed to be prevented from further aggregation and crystallization by complexing with Congo red on their surfaces. Some loose triple 6/1 helical strands (native elementary fibrils) are also discernible. They represent the first native (1--- 3)-beta-D-glucan elementary fibrils depicted by electron microscopy. The effects of Congo red on growth and the wall structure in normal cells and regenerating protoplasts in solid medium can be explained by the presence of a complex which the dye forms with (helical) chain parts of the glucan network and which results in a loss of rigidity by a blocked lateral interaction between the helices. PMID- 1417415 TI - The role of tungstate and/or molybdate in the formation of aldehyde oxidoreductase in Clostridium thermoaceticum and other acetogens; immunological distances of such enzymes. AB - Besides Clostridium thermoaceticum and C. formicoaceticum other resting acetogenic clostridia such as C. aceticum and C. thermoautotrophicum and to a lesser extent non-clostridial acetogens such as Butyribacterium methylotrophicum and Eubacterium limosum were able to reduce propionate to propanol at the expense of carbon monoxide or formate. Methylviologen usually increased the reduction rate. Ten microM molybdate in the growth medium decreased this capability for C. thermoaceticum but increased it or had no effect for the other organisms. Ten microM tungstate in the growth medium increased the aldehyde oxidoreductase activity in all organisms. Crude extracts of C. thermoaceticum cells grown in the presence of 10 microM or 1 mM molybdate showed by ELISA the same or even a 4 fold concentration of aldehyde oxidoreductase in the latter case. However, the enzymic activity was very low in both cases. Omission of dithionite in the growth medium diminished the antigen by a factor of about 8. The immunological distance between the enzyme from C. thermoaceticum and C. thermoautotrophicum was rather low but very large to C. formicoaceticum and undeterminably large to the other organisms. PMID- 1417417 TI - Electron microscopic examination of sporulation-deficient mutants of the fission yeast Schizosaccharomyces pombe. AB - A homothallic haploid strain of the fission yeast Schizosaccharomyces pombe initiates sexual reproduction (mating, meiosis and sporulation) in nitrogen-free sporulation medium. Cellular fine structures of eleven sporulation-deficient mutants (spo2, spo3, spo4, spo5, spo6, spo13, spo14, spo15, spo18, spo19 and spo20) of S. pombe in sporulation medium were examined by serial section-electron microscopy. The striking features of these spo mutants were: 1) the disappearance of the spindle pole bodies (SPBs) after the second meiotic division, and 2) the accumulation of unorganized structures. Based on histochemical staining, these structures were presumably unorganized spore wall precursors. In some mutants (spo3, spo5, spo6, spo19 and spo20), diploid zygotes contained four spore-like bodies which had walls similar to complete spore walls but failed to enclose any nuclei. After completion of the second meiotic division the nuclei were abnormally distributed in zygotic diploid cells. In the spo5, spo13, spo14, spo15 and spo19 mutants, the nuclei remained attached to each other. In spo5 and spo19, the inner membrane of the nuclear envelope was separated, but its outer membrane was shared by two sister nuclei. These observations suggest that the spo+ gene products play important roles in spatial and temporal organization of cellular structures during ascospore development. PMID- 1417418 TI - Transformation of synthetic pyrethroid insecticides by a thermophilic Bacillus sp. AB - Employing a mineral salts medium containing Tween 80 as the primary carbon source, a strain of Bacillus stearothermophilus was isolated which was able to hydrolyse selected second and third-generation pyrethroids to non-insecticidal products. Of a range of pyrethroid insecticides the trans-isomer of permethrin was the most readily transformed by this microbial isolate, whilst flumethrin was the least. 3-Phenoxybenzoic acid and the respective halovinyl or haloacid moieties were detected as the major hydrolytic products of the pyrethroids. It is believed that 3-phenoxybenzoic acid was formed from 3-phenoxybenzyl alcohol which was not however detected as an intermediate in these systems. 3-Phenoxybenzoic acid was further transformed to 4-hydroxy-3-phenoxybenzoic acid. A potential metabolic pathway has been described. PMID- 1417416 TI - Molecular interaction between bacteriophage and the gram-negative cell envelope. PMID- 1417419 TI - 2-Hydroxyglutaryl-CoA dehydratase from Fusobacterium nucleatum (subsp. nucleatum): an iron-sulfur flavoprotein. AB - Anaerobically prepared cell-free extracts from Fusobacterium nucleatum contain 2 hydroxyglutaryl-CoA dehydratase with a specific activity of 20 nkat mg-1. The enzyme was purified 24-fold to a specific activity of 480 nkat mg-1 by anion exchange chromatography, gel filtration and chromatography on Blue-Sepharose. The activity of the purified enzyme was strictly dependent on the reductant Ti(III)citrate and stimulated 25-fold by 0.15 mM ATP and 5 mM MgCl2. ATP is hydrolysed to ADP during incubation with 2-hydroxyglutaryl-CoA dehydratase in the presence or absence of the substrate. The enzyme is extremely sensitive towards oxygen and is inhibited by 10 microM chloramphenicol, 10 microM 2,4-dinitrophenol or 0.15 mM hydroxylamine. The pure enzyme consists of three subunits alpha (49 kDa), beta (39 kDa) and gamma (24 kDa) in approximately equal amounts. In this respect the enzyme differs from the related 2-hydroxyglutaryl-CoA dehydratase from Acidaminococcus fermentans and lactyl-CoA dehydratase from Clostridium propionicum both of which are composed of only two subunits with sizes comparable to those of alpha and beta but require an additional protein for activity. The relative molecular mass of the native enzyme of about 100 kDa suggests a trimeric alpha beta gamma-structure. The homogeneous enzyme contains riboflavin (0.5 mol/112 kDa), iron and sulfur (3.5 mol/112 kDa each). Polyclonal antibodies directed against the 2-hydroxyglutaryl-CoA dehydratase from A. fermentans did not crossreact with cell free extracts or purified dehydratase from F. nucleatum. A comparison of the N-terminal amino acid sequences of the dehydratase subunits from A. fermentans and F. nucleatum, however, showed some similarities in the beta-subunits. PMID- 1417420 TI - Characterization of a carbofuran-degrading bacterium and investigation of the role of plasmids in catabolism of the insecticide carbofuran. AB - A bacterium capable of using the carbamate insecticide carbofuran as a sole source of carbon and energy, was isolated from soil. The ability to catabolise carbofuran phenol, produced by cleavage of the carbamate ester linkage of the insecticide, was lost at very high frequency when the bacterium was grown in the absence of carbofuran. Plasmid analyses together with curing and mating experiments indicated that the presence of a large plasmid (pIH3, greater than 199 kb) was required for the degradation of carbofuran phenol. PMID- 1417421 TI - [Clinical and lesion-related bases of alcoholic brain damage]. AB - Alcohol-induced brain damage is known since long, with classical descriptions of lesions. There is no constant correlation between them and any of the clinical presentations of chronic intoxication. New neuroimaging techniques, neuropsychology and basic investigation have supplied with new data. The so called alcoholic dementia and its possible reversibility are major issues of this problem. This paper reviews radiological, pathological, vascular and neuropsychological studies related to this point. PMID- 1417422 TI - [Visual constructive deficits and coma depth]. AB - The present study has the purpose of relating the capacities of visual retention with the Benton Visual Retention Test and the level of coma depth, which is measured with the GCS (Glasgow Coma Scale). 31 subject suffering cranioencephalic damage admitted to the intensive care unit (ICU) have been studied. GCS scores were obtained during their stay in the intensive care unit and the Benton Visual Retention Test was administered after hospital discharge. The procedure followed consists in comparing the performance of subjects with higher GCS scores to subjects with lower values when executing administration. A of form C of BVRT. We could conclude as follows: firstly that BVRT is a useful tool to detect the existence of brain damage; secondly, indexes of brain damage presence with BVRT are: a low figure in correct design, more errors, less errors in distortion and rotation; more errors in the left visual hemifield. Thirdly, the depth of coma is a good prognosis index on BVRT execution and in consequence of visuo-constructive abilities. PMID- 1417423 TI - [Experimental model of Parkinson disease: mechanisms and anatomo- pathological characteristics of MPTP neurotoxicity]. AB - MPTP administration induces a fairly selective lesion of substantia nigra dopaminergic neurons both in animals and humans. This characteristic of MPTP has led to the best available model of Parkinson's disease and neuronal degenerations. MPTP toxicity is actually provoked by MPP+ which results after oxidation by MAO-B. Possible mechanism of action of MPP+ include: 1) Mitochondrial lesion. 2) Free radicals generation. 3) Trapping of MPP+ by highly melanized neurons. This article reviews the mechanisms of toxicity by MPTP and its neuropathological characteristics. PMID- 1417424 TI - [Nuclear syndrome of the oculomotor nerve caused by a mesencephalic infarction confirmed by MRI]. AB - The nuclear syndrome of the third nerve was first described in 1981. It has the very characteristic disturbance of an ophthalmoplegia with complete ipsilateral third nerve palsy associated with paresis of elevation in contralateral eye. This particularly presentation is due to the innervation of the superior rectus which comes mainly from the contralateral oculomotor nucleus. As associated signs were described contralateral cerebellar and or pyramidal syndromes, uni or bilateral parasympathetic disfunction and sometimes gaze disorders. The etiology es usually a vascular damage (ischemic most frequently) located in mesencephalon. We report on a case of a 60 years old man who developed acute nuclear ophthalmoplegia of the third right nerve accompanied with cerebellar and pyramidal syndrome and focal asterixis in left extremities. MRI showed an ischemic lesion in right paramedial mesencephalic territory with extension to the ipsilateral thalamic region. Pyramidal and cerebellar syndromes and asterixis disappeared in a few weeks, while ophthalmoplegia remained unchanged. Semiologic characteristics and anatomic basis of the nuclear oculomotor syndrome which allow to make the differential diagnosis between this syndrome and intra-axial fascicular disturbances of the third nerve (Weber, Claude and Benedikt syndromes) are discuss. PMID- 1417425 TI - [Benign evolution of a spontaneous vermian hematoma using conservative treatment]. AB - Spontaneous intracerebellar haematomas are a relatively unusual cause of haemorrhagic stroke. The uncommon variety of vermian haematomas (5%) represents a serious diagnostic and treatment challenge and its outcome is generally poor, being the result of rapid elevation of intracranial pressure and brainstem compression. A rare case of spontaneous vermian haematoma with benign course without surgery is reported, including the results of neuroimaging tests. PMID- 1417426 TI - [Post-concussion syndrome: how much is organic and how much psychogenic?]. PMID- 1417427 TI - Treatments of depression and the functional capacity to work. AB - This study evaluated the effects of antidepressants and psychotherapy on work impairment in depressed patients. Original databases from 10 published treatment studies were compiled and analyzed (N = 827). Functional work impairment was common at baseline, manifested by unemployment (11%) or on-the-job performance problems (absenteeism, decreased productivity, interpersonal problems, 44%). Generally, work outcomes were good when treatment was symptomatically effective, but the trajectories of work restoration and symptom remission were different, with work recovery appearing to take considerably longer. Relapse was an important determinant of long-term occupational outcome, particularly for seriously ill patients for whom relapse meant rehospitalization or other profound social disruption. Affective impairment was distinguished from functional impairment, with the former characterizing milder depression and the latter characterizing moderate to severe depression. Some methodological recommendations are discussed. PMID- 1417428 TI - Five-year outcome for maintenance therapies in recurrent depression. AB - After conducting a randomized, 3-year maintenance trial in 128 patients with recurrent depression who had responded to combined short-term and continuation treatment with imipramine hydrochloride and interpersonal psychotherapy, we asked those individuals who survived the 3-year trial receiving active medication (with or without psychotherapy) to continue in a 2-year additional randomized trial of active medication vs placebo. The question was whether maintaining antidepressant medication at the dosage used to treat the acute episode beyond 3 years would continue to provide a significant prophylactic effect compared with medication discontinuation after the 3 years of effective maintenance treatment. Survival analysis demonstrated a highly significant continued prophylactic effect for active imipramine hydrochloride treatment maintained at an average dose of 200 mg. We conclude that active imipramine treatment is an effective means of preventing recurrence beyond 3 years and that patients with previous episodes less than 2 1/2 years apart, therefore, merit continued prophylaxis for at least 5 years. PMID- 1417429 TI - Cognitive therapy and pharmacotherapy for depression. Singly and in combination. AB - Cognitive therapy and imipramine hydrochloride tricyclic pharmacotherapy, each singly and in combination, were compared in the treatment of nonpsychotic, nonbipolar depressed outpatients. One hundred seven patients were randomly assigned to 12 weeks of active treatment; 64 patients completed the full course of treatment. Rates of attrition were high but not differential. Cognitive therapy and pharmacotherapy did not differ in terms of symptomatic response, either in the primary analyses or in secondary analyses restricted to more severely depressed outpatients. Initial severity did predict response within pharmacotherapy alone, but not within cognitive therapy. Combining cognitive therapy with pharmacotherapy did not markedly improve response over that observed for either modality alone, although such nonsignificant differences as were evident did favor the combined treatment. Two patients died as a consequence of suicide attempts, both of which involved study medication. PMID- 1417431 TI - The course of depression in adult outpatients. Results from the Medical Outcomes Study. AB - OBJECTIVE: To compare the course of depression during a 2-year period in adult outpatients (n = 626) with current major depression, dysthymia, and either both current disorders ("double depression") or depressive symptoms with no current depressive disorder. METHODS: Depressed patients visiting 523 clinicians (mental health specialists and general medical providers) were identified using a two stage screening procedure including the Diagnostic Interview Schedule. The course of depression was assessed in 2 follow-up years with a structured telephone interview based on the format of the Diagnostic Interview Schedule. RESULTS: Baseline severity of depressive symptoms was greatest in patients with double depression, but initial functional status was poor in those with dysthymia with or without concurrent major depression. Patients with dysthymia had the worst outcomes, those with current major depression alone had intermediate outcomes, and those with subthreshold depressive symptoms had the best outcomes. Even the latter group, however, had a high incidence (25%) of major depressive episode over 2 years. Initial depression severity and level of functional status accounted for more explained variance in outcomes than did type of depressive disorder. CONCLUSIONS: The findings emphasize the poor prognosis associated with dysthymia even in the absence of major depression; the prognostic significance of subthreshold depressive symptoms; and the clinical significance of assessing level of severity of symptoms as well as functional status and well-being, regardless of type of depressive disorder. PMID- 1417430 TI - Course of depressive symptoms over follow-up. Findings from the National Institute of Mental Health Treatment of Depression Collaborative Research Program. AB - We studied the course of depressive symptoms during an 18-month naturalistic follow-up period for outpatients with Major Depressive Disorder treated in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. The treatment phase consisted of 16 weeks of randomly assigned treatment with the following: cognitive behavior therapy, interpersonal therapy, imipramine hydrochloride plus clinical management (CM), or placebo plus CM. Follow-up assessments were conducted at 6, 12, and 18 months after treatment. Of all patients entering treatment and having follow-up data, the percent who recovered (8 weeks of minimal or no symptoms following the end of treatment) and remained well during follow-up (no Major Depressive Disorder relapse) did not differ significantly among the four treatments: 30% (14/46) for those in the cognitive behavior therapy group, 26% (14/53) for those in the interpersonal therapy group, 19% (9/48) for those in the imipramine plus CM group, and 20% (10/51) for those in the placebo plus CM group. Among patients who had recovered, rates of Major Depressive Disorder relapse were 36% (8/22) for those in the cognitive behavior therapy group, 33% (7/21) for those in the interpersonal therapy group, 50% (9/18) for those in the imipramine plus CM group, and 33% (5/15) for those in the placebo plus CM group. The major finding of this study is that 16 weeks of these specific forms of treatment is insufficient for most patients to achieve full recovery and lasting remission. Future research should be directed at improving success rates of initial and maintenance treatments for depression. PMID- 1417432 TI - The course of major depression in the offspring of depressed parents. Incidence, recurrence, and recovery. AB - The 2-year course, first onset (incidence), recurrence, and recovery of major depression in 174 offspring at high and low risk for major depression were studied. A variety of predictors of course were examined, including parental diagnosis, demographic and clinical characteristics of the family and offspring, comorbidity and social functioning in offspring, and family risk factors. The 2 year incidence rate was 8.5%. All of the incident cases of major depression occurred in offspring of depressed parents. Additional predictors of incidence were a preceding diagnosis of conduct disorder and subclinical symptoms of depression. The recurrence rate results are tentative because of the small sample. The 2-year recurrence rate was 16.1%. Predictors of recurrence were a previous comorbid diagnosis of dysthymia or problems in social functioning. By the end of 2 years, the majority of offspring (87%) had recovered. The mean number of weeks to recovery was 54 in the offspring of depressed parents and 23 in the offspring of nondepressed parents. Offspring with an onset of major depression at age 13 years or younger, who were exposed to divorce in the family or who had been exposed to more than one parental depressive episode, had significantly more protracted times to recovery. We conclude that there are different predictors of incidence of major depression, its recurrence, and time to recovery in offspring, and that parental depression has an impact on the course in offspring. PMID- 1417433 TI - Differential relapse following cognitive therapy and pharmacotherapy for depression. AB - Patients successfully treated during a 3-month period with either imipramine hydrochloride pharmacotherapy, cognitive therapy, or combined cognitive pharmacotherapy were monitored during a 2-year posttreatment follow-up period. Half of the patients treated with pharmacotherapy alone continued to receive study medications for the first year of the follow-up. All other patients discontinued treatment at the end of the acute treatment phase. Patients treated with cognitive therapy (either alone or in combination with medication) evidenced less than half the rate of relapse shown by patients in the medication--no continuation condition, and their rate did not differ from that of patients provided with continuation medication. It appears that providing cognitive therapy during acute treatment prevents relapse. Whether this preventive effect extends to recurrence remains to be determined. PMID- 1417434 TI - Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. AB - The course of illness of 431 subjects with major depression participating in the National Institute of Mental Health Collaborative Depression Study was prospectively observed for 5 years. Twelve percent of the subjects still had not recovered by 5 years. There were decreasing rates of recovery over time. For example, 50% of the subjects recovered within the first 6 months, and then the rate of recovery declined markedly. Instantaneous probabilities of recovery reflect that the longer a patient was ill, the lower his or her chances were of recovering. For patients still depressed, the likelihood of recovery within the next month declined from 15% during the first 3 months of follow-up to 1% to 2% per month during years 3, 4, and 5 of this follow-up. The severity of current psychopathology predicted the probability of subsequent recovery. Subjects with moderately severe depressive symptoms, minor depression, or dysthymia had an 18 fold greater likelihood of beginning recovery within the next week than did subjects who were at full criteria for major depressive disorder. Many subjects who did not recover continued in an episode that looked more like dysthymia than major depressive disorder. PMID- 1417435 TI - Depressive symptoms as relative and attributable risk factors for first-onset major depression. AB - Using longitudinal data from a community study of 9900 adults drawn from four sites in the United States and interviewed twice, 1 year apart, we investigated the predictors of first-onset major depression. Using odds ratios to estimate relative risk, we found that persons with depressive symptoms, compared with those without such symptoms, were 4.4 times more likely and persons with dysthymia were 5.5 times more likely to develop a first-onset major depression during a 1-year period. The lifetime prevalence rate for depressive symptoms was 24%. The attributable risk is a compound epidemiologic measure that reflects both the relative risk associated with depressive symptoms (4.4) and the prevalence of exposure to that risk (24%). It is a useful measure to document the burden of a risk to the community, and it was determined to be greater than 50%. Thus, more than 50% of cases of first-onset major depression are associated with prior depressive symptoms. The high prevalence of depressive symptoms in the community and their strong association with first-onset major depression make them important from a public health perspective. Because depressive symptoms are often unrecognized and untreated in clinical practice, we conclude that their identification and the development of effective treatments could have implications for the prevention of major depression. PMID- 1417437 TI - The course, morbidity, and costs of depression. PMID- 1417436 TI - Stability of psychiatric diagnoses. An application to the affective disorders. AB - In the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2226 first-degree relatives of 612 probands. A second, "blind" reassessment of all relatives was attempted 6 years after the initial evaluation. We report on a final sample of 1629 relatives assessed twice using the Schedule for Affective Disorders and Schizophrenia-Lifetime version. We summarize methods for using stability of diagnosis to model the relationship between clinical covariates and the probability of being a true case. Moreover, we define an index of caseness that can be used to narrow the criteria for who is a case. Of those positive for major depressive disorder at initial evaluation, 74% were positive (on a lifetime basis) at follow-up (ie, were stable). There is a gradient: 48% of those who had three symptoms and no treatment were stable, compared with 96% of those with eight symptoms and treatment. For major depressive disorder, we found the caseness index for those with lifetime mania more severe than that of nonbipolar patients, with those who had hypomania being intermediate. A hierarchical analysis indicated that bipolar I tends to be diagnosed as schizoaffective-manic across occasions, and vice versa. This is consistent with the prior familial analyses that suggest these two diagnoses be combined into a single bipolar phenotype. The analysis for major depressive disorder indicates that caseness appears to represent quantitative, rather than qualitative, differences, with no natural cutoff to identify distinct subgroups. Finally, we discuss implications including utility in genetic analyses, estimation of incidence or prevalence allowing for diagnostic error, and examination of cohort effects. PMID- 1417438 TI - The hybrid laboratory. The clinical laboratory of the 1990s is a synthesis of the old and the new. PMID- 1417439 TI - The impact of transplantation on the clinical laboratory. Experience at the University of Nebraska with bone marrow and liver transplantation. AB - The number of both bone marrow and solid organ transplantation programs has increased significantly during the past several years. The implementation of these programs and their growth have had a significant impact on the clinical laboratories that are involved in the support of these programs. Between 1983 and 1985, two major organ transplantation programs were implemented at the University of Nebraska Medical Center, Omaha. The clinical laboratories at the University of Nebraska Medical Center have seen a 217% increase in procedure volume and a 165% increase in full-time equivalents during an 8-year period from 1983 to 1991 as a result of these programs. The laboratory procedures that are performed on patients who are undergoing transplantation currently generate approximately $9 million in charges per year. In the present article, I discuss the effect of bone marrow and liver transplantation programs on the entire laboratory and individual laboratory sections. PMID- 1417440 TI - An alternate origin for the placental isoenzyme of alkaline phosphatase. AB - By means of an electrofocusing technique, the serum specimens of pregnant women routinely revealed three bands of alkaline phosphatase (ALP) that were released by placental syncytiotrophoblast, germ cell (ovary), and fetal intestine at pl of 4.73, 4.65, and 4.55, respectively. When defining reference ranges for ostensibly healthy persons of all decades of age and investigating patients with elevated total ALP activity, we found the isoenzyme at pl 4.73 to be above the established reference range in some nonpregnant women and in men. Evidence suggests that T lymphocytes from whole blood or in vivo tissue were the origin of this pl 4.73 ALP band; the isoenzyme being released during cell lysis, in cellular turmoil from any cause, or when active cell division occurs. A designation of lymphocyte ALP is proposed for this ALP band that is observed in a broad group of diseases associated with abnormal lymphocyte function. PMID- 1417441 TI - Naked megakaryocyte nuclei as an indicator of human immunodeficiency virus infection. AB - Compact, lobulated megakaryocyte nuclei, apparently denuded of cytoplasm (naked nuclei), have been reported to be markedly increased in the bone marrow of persons infected with human immunodeficiency virus (HIV). We have confirmed this observation and have developed a useful diagnostic index, the naked nucleus ratio, to characterize the bone marrow of individuals who are infected with HIV. The naked nucleus ratio, calculated as the average number of naked nuclei per high-power field divided by the average number of intact megakaryocytes per high power field, has a sensitivity of 97.9% and a specificity of 96.4% for patients with HIV infection. In our patients with a 62.6% prevalence of HIV infection, the predictive value of a positive test was 97.9% and the predictive value of a negative test was 96.4%. An increase in the naked nucleus ratio above 10%, without specific changes in the bone marrow, should raise or may confirm the suspicion of HIV infection. PMID- 1417442 TI - Comparison of hemoglobin and red blood cell distribution width in the differential diagnosis of microcytic anemia. AB - In a total group of 415 subjects (100 normal controls, 115 with iron deficiency anemia, 100 with the alpha-thalassemia trait, and 100 with the beta-thalassemia trait), the following indexes were analyzed: hemoglobin distribution width, red blood cell distribution width (RDW)-coefficient of variation, and RDW-SD. The hemoglobin distribution width and RDW-coefficient of variation were examined with a laser light scattering system (Technicon H1), whereas the RDW-SD was determined with an impedance autoanalyzer (Sysmex M-2000). All of these parameters helped, to some extent, in the differential diagnosis of microcytic anemia. However, our data suggested a low RDW-SD might provide significantly more value in differentiating thalassemia traits from iron deficiency anemia, as well as from normal controls, while the hemoglobin distribution width gave no help in the differential diagnosis between iron deficiency anemia and the beta-thalassemia trait. PMID- 1417443 TI - Distribution of tritiated cocaine in selected genital and nongenital organs following administration to male mice. AB - STUDY OBJECTIVE: To determine the distribution of cocaine administered to male mice in selected extragenital and genital organs and to investigate its possible binding to sperm. DESIGN: Twenty-seven sexually mature virus-free albino male mice were used in various experiments whereby following intravenous injection of tritiated cocaine hydrochloride, radioactivity was determined in several extragenital and genital organs, as well as sperm. RESULTS: Radioactivity was detected in all of the organs that were tested, and the highest concentrations per milligram of tissue were found in the kidney and epididymis. Removal of the sperm from the epididymis significantly reduced the radioactivity of the organ. The spermatozoa that were isolated on glass filters showed a linear correlation vs radioactivity (r = .93). CONCLUSIONS: Radioactivity is distributed to several organs, including the genital tract, and is found in association with sperm after in vivo administration of tritiated cocaine. These results may explain the mechanism underlying a male-mediated teratogenesis, which has been observed in animals that were exposed to cocaine, and they raise a possibility that the spermatozoa may carry cocaine into the oocyte during fertilization. PMID- 1417444 TI - Vascular proliferation of the thyroid. A complication of fine-needle aspiration. AB - Fine-needle aspiration (FNA) of the thyroid has a low morbidity rate, with hematoma formation being the most commonly encountered complication. We describe two cases of exuberant vascular proliferation within the thyroid gland, one resembling a cavernous hemangioma and the other with similar changes but with areas of papillary endothelial hyperplasia. Both lesions occurred in patients with a recent history of FNA prior to the thyroidectomy procedure. The vascular proliferation was interpreted as organizational changes in a hematoma secondary to the FNA. These cases, in conjunction with a recent case of Masson's vegetant intravascular hemangioendothelioma complicating thyroid FNA, expand the literature on vascular proliferations that may develop subsequent to thyroid FNA. PMID- 1417445 TI - Intrapulmonary neuroglial heterotopia. AB - Nonteratomatous intrapulmonary neuroglial heterotopia not associated with birth trauma or frank vascular embolization has been described rarely. This article briefly reviews the literature, and presents two additional cases of intrapulmonary neuroglial heterotopia. We found 14 cases in the literature. Twelve of these cases had central nervous system disruption, where neuroglial elements were in direct contact with amniotic fluid. Several hypotheses have been proposed, including fetal aspiration of detached neural fragments within amniotic fluid, neural crest migration defects, and vascular embolization with implantation. Of our two cases, one represents the first occurrence where central nervous system abnormalities were secondary to mechanical disruption, rather than to a primary neural tube defect. Our second case represents the youngest documented occurrence (17 weeks gestation) of intrapulmonary neuroglial heterotopia. Additionally, immunohistochemical studies were performed on these lesions, the results of which favor their neural origin. We present these findings and suggest they support the aspiration mechanism for neuroglial heterotopia in lung tissue. PMID- 1417446 TI - Postcapillary venule-like transformation of peritubular capillaries in acute renal allograft rejection. An ultrastructural study. AB - To describe ultrastructural changes in renal peritubular capillaries during acute allograft rejection, biopsy specimens from five allografts with acute rejection were studied electron microscopically and compared with control specimens. The thickness, cross-sectional area, and luminal circumference of capillary endothelium were estimated morphometrically. Thickening of endothelial cells, loss of fenestration, increase in endothelial cell organelles, increased adherence and passage of lymphocytes and monocytes, and defects in the endothelial lining were demonstrated. The luminal circumference representing the size of the capillary was not changed. A balloonlike fragmentation of endothelial cells was sometimes observed around lymphocytes, suggesting cytotoxic injury to capillaries. The observations indicate that during rejection-induced endothelial activation, peritubular capillaries exhibit postcapillary venule-like transformation that enhances the influx of inflammatory cells into the kidney allograft. PMID- 1417447 TI - Primary smooth-muscle tumors of the ovary. A clinicopathologic study of four leiomyomas and two mitotically active leiomyomas. AB - A series of six primary ovarian smooth-muscle tumors were studied. Four were ordinary leiomyomas and two were neoplasms with prominent mitotic activity, which we designated mitotically active leiomyomas. The patients' ages ranged from 42 to 76 years (median, 50.5 years). In five of six patients, synchronous leiomyomas of the uterus were also present. In three patients, the ovarian tumor was an incidental finding. The maximum dimension of the ovarian tumors ranged from 0.3 to 20.0 cm (median, 3.0 cm). Three of the tumors originated in the hilar region, one on the cortical surface, and in two the exact location within the ovary could not be determined. Follow-up was available on all six patients. None developed local recurrence or metastasis from their ovarian tumor, including the two patients with mitotically active leiomyoma whose postoperative follow-up intervals were 3.8 and 7.7 years. PMID- 1417448 TI - Hodgkin's disease presenting as spontaneous splenic rupture. AB - Hodgkin's disease presenting as spontaneous splenic rupture is rare. A 46-year old man with a 4-week history of fever, chills, and night sweats developed sudden abdominal pain and hypotension. At surgery, an enlarged, ruptured spleen with a nodular surface was found. Histologically, there was diffuse infiltration of the red pulp by mixed-cellularity Hodgkin's disease with patchy involvement of the white pulp. The histopathologic findings in the three previously reported cases are all dissimilar to this. These differences most likely represent rupture occurring at different stages of splenic infiltration by Hodgkin's disease. PMID- 1417449 TI - Granular cells in a cellular neurilemmoma. AB - In this article, we describe a case of a cellular neurilemmoma with focal granular cell elements. The Schwann cells showed S100 and Leu-7 immunoreactivity. The granular cells were periodic acid-Schiff-positive, diastase resistant with strong S100 immunoreactivity. Electron microscopy showed electron dense, heterogeneous granules in the granular cells and interdigitating processes and elongated nuclei of the Schwann cells. Although many granular cell tumors are believed to be derived from Schwann cells, neoplasms with both elements are rarely presented. PMID- 1417450 TI - Complications of atherosclerosis in cholesterol-fed rhesus monkeys. PMID- 1417451 TI - The application of backpropagation neural networks to problems in pathology and laboratory medicine. AB - Neural networks are a group of computer-based pattern recognition technologies that have been applied to problems in clinical diagnosis. This review focuses on one member of the group of neural networks, the backpropagation network. The steps in creating a backpropagation network are (1) collecting adequate training facts, (2) choosing the specific network structure, (3) training the network, and (4) cross-validating the trained network. The first published applications of backpropagation networks to problems in pathology and laboratory medicine have appeared recently. These applications are in the areas of image analysis and interpretation of laboratory results, and they demonstrate the feasibility of the approach. PMID- 1417452 TI - [Aqueous chloramine T solutions as disinfectants: chemical composition, reactivity and toxicity]. AB - In aqueous solutions of Chloramine T (CAT), caused by dissociation, hydrolysis and disproportionation processes, seven different kinds of molecules emerge (HOCl, OCl-, R-NCl-, R-NHCl, R-NCl2, R-NH2, and R-NH- [R = CH3-C6H4-SO2]). Their equilibrium concentrations have been calculated using an iteration process (polynom of 4th degree) as a function of cCAT (0.003-10%) and pH (0-14): The (absol.) concentration of "free chlorine" ([HOCl] + [OCl-]) is surprisingly low showing a maximum concentration of HOCl in the whole concentration and pH range of only 2 . 10(-7) moles/l (0.014 ppm). The relative equilibrium concentrations of the N-chlorinated toluene sulfonamide species R-NCl-, R-NHCl, and R-NCl2, virtually alone responsible for the oxidizing and by this also disinfecting properties, owing to the extremely low concentration of free chlorine, are influenced in the concentration range relevant for practice (greater than 0.1%) only by the pH-value: At pH greater than 7 the whole oxidation capacity is present as R-NCl- (pH 7: 99.6%; pH 8: 99.96%), while at pH less than 3 it is formed by R-NHCl and R-NCl2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417453 TI - [Local anesthetics. 99. Synthesis and local anesthetic actions of alkoxyphenylcarbamates]. AB - Within the framework of studying the influence of alterations of the connecting chain in the group of local anaesthetics a series of 24 compounds of 1 propoxymethyl-2-(1-pyrrolidinyl), 2-(1-piperidino)-, and 2-(1-perhydroazepinyl) ethyl esters of o- and m-alkoxyphenylcarbamic acid were prepared. Studied compounds show a high index of relative local anaesthetic activity as compared to the standards cocaine and procaine, at a relatively low acute toxicity. PMID- 1417454 TI - Synthesis and antimicrobial activity of 3-(substituted-phenyl)-sydnones. AB - 3-(3 or 4-Acetylphenyl)-sydnones 7, 8 have been synthesized by formation of the glycines 3, 4, followed by nitrosation to 5, 6 and cyclization with acetic anhydride to sydnones. Sydnone derivatives carrying chalcone moieties 15, 16 were prepared by formation of the chalcone analogues 11, 12 through condensation of the glycines 3, 4 with the appropriate aldehydes, followed by the reactions applied for the preparation of 7, 8. The sydnone derivatives were screened for antimicrobial activities. PMID- 1417455 TI - Pyrrylphenylethanones related to cathinone and lefetamine: synthesis and pharmacological activities. AB - The synthesis of various pyrrylphenylethanones resembling cathinone and lefetamine is described starting from 2-chloro-1-(1-methyl-1H-pyrrol-2-yl)-2 phenylethan-1-one. Some derivatives showed good antinociceptic activity, comparable to that of morphine. The neuropsychopharmacological profile of title compounds has been also studied to explore their action on C.N.S. PMID- 1417456 TI - New indole and triazino[5,4-b]indol-4-one derivatives: synthesis and studies as inotropics and inhibitors of blood platelet aggregation. AB - New triazino[5,4-b]indol-4-one derivatives carrying amino groups in position 3 were synthetized and tested as inotropic agents and inhibitors of platelet aggregation. 2h, 2p, 5p, and 6g are the most active as inotropic agents. Compounds were tested as inhibitors of platelet aggregation induced by adenosine 5'-diphosphate (ADP) and arachidonic acid (AA) (guinea pig whole blood). 2k, 2p, 5o, 6d, 6m, and 6o are the most active as inhibitors of the platelet aggregation induced by AA. 6d, 6h, and 6o are most active compounds also in the aggregation induced by ADP. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on compounds 2b, 2d, 2f, 2g, 2h, 2i, 2k, 2m, 2o, 2p, 2r, 5i, 5j, 5k, 5r, and 5f, which inhibit platelet aggregation induced by AA. None of the compounds tested turned out to be selective inhibitors. Compounds 2h and 2p showed both inotropic and platelet aggregation inhibiting activity. PMID- 1417457 TI - [Actions of new iminium compounds on bacteria and fungi. 27. Synthesis of 1-n decyl-2-phenyl-3-(n-alkylthiomethyl)- and 1-n-decyl-2-phenyl-3-(n alkoxymethyl)imidazolium chlorides]. AB - The imidazolium compounds 1-3 were prepared by quaternization of 1-decyl-2 phenylimidazole with the pertinent chloromethyl-n-alkyl ethers. 1-3 were tested for their antibacterial and antimycotic efficacies. PMID- 1417458 TI - New cardiotonic agents related to amrinone: synthesis of 1,2-dihydro-5 arylpyridin-2-ones. AB - For development of new cardiotonic agents a series of 5-aryl-3,4-dihydropyridin 2(1H)-ones, related to amrinone have been prepared from methylquinolines, 2 arylacetic acid or 3-arylethanones by direct aminomethylenation and subsequent condensation-cyclization with malonamide and cyanacetamide in classic basic media or phase-transfer catalysis, in good to excellent yields. Preliminary pharmacological assays have shown that these compounds, especially 5h and 5i, have a remarkable cardiotonic effect and present a selective inhibition of PDE III/PDE-I isolated from cat heart. PMID- 1417459 TI - Synthesis and antiprotozoal properties of 1,2,6-thiadiazine 1,1-dioxide derivatives. AB - The synthesis and spectroscopical data of 1,2,6-thiadiazine 1,1-dioxides, designed as antiprotozoal agents, are reported. The in vitro trichomonacidal and trypanocidal activities of new compounds and their precursors were evaluated against Trichomonas vaginalis and Trypanosoma cruzi. The chemoprophylactic activity on mice treated with blood infected with T. cruzi and their mortality percentage were tested. Compounds 2 and 8b show a higher chemoprophylactic activity and lower mortality percentage than Nifurtimox used as reference drug. PMID- 1417460 TI - Aminopeptidase inhibitory properties and analgesic activity of (2S,3R)-3,7 diamino-2-hydroxy-heptanoic acid containing tripeptide analogues of the N terminal tripeptide of probestin. AB - (2S,3R)-3,7-Diamino-2-hydroxy-heptanoyl-Leu-Pro-OH [(2S,3R)-DAHHA-Leu-Pro-OH, 4], analogue of the N-terminal tripeptide of probestin, has been synthesized, and tested as inhibitor of AP-B, Leu-AP, AP-M, and enkephalin-degrading APs, and as analgesic. In order to establish structure-activity relationships the dipeptide (2S,3R)-DAHHA-Pro-OH (5) and the tripeptide (2S,3R)-DAHHA-Ala-Pro-OH (6) were also prepared. Compounds 4 and 6 were potent and selective inhibitors of enkephalin-degrading APs and showed a prolonged antinociceptive effect. PMID- 1417461 TI - Bioavailability study of two different verapamil formulations. AB - Relative bioavailability and bioequivalence of two oral verapamil preparations were investigated (dosage 80 mg, film-coated tablets as reference, dragees as test formulation). The clinical study was performed in a 2-period-cross-over design with 16 male healthy volunteers (mean age 28.8 +/- 3 years). The active metabolite norverapamil was included in the investigation. To assess bioequivalence several pharmacokinetic characteristics (i.e. AUC(o-oo), Cmax, tmax) were taken into account. Shortest 90% confidence intervals were calculated based on parametric (ANOVA, ANOVAlog) and non-parametric (Wilcoxon, Mann-Whitney) statistical tests. A positive decision for bioequivalence was accepted if the confidence intervals did not exceed the limits of 80-120% for AUC and 70-130% for Cmax. A mean relative bioavailability of 127% for the test preparation was found. Thus, bioavailability of the dragees is marked higher than bioavailability of the film-coated tablets. PMID- 1417462 TI - Some N-Mannich bases of 2-benzoxazolinones and their analgesic activities. PMID- 1417463 TI - Applying psychometric criteria to functional assessment in medical rehabilitation: III. Construct validity and predicting level of care. AB - A discriminant analysis was performed using Rasch ability estimates derived from four Patient Evaluation and Conference System (PECS) subscales, to distinguish among the functional independence and impairment profiles exhibited by patients admitted into any of three levels of medical rehabilitation delineated by the National Association of Rehabilitation Facilities (NARF): (1) inpatient hospital, (2) atypical nursing home (intermediate), or (3) day program. Two discriminant functions accounted for 91% and 9% of the between-group variance, respectively. Cross-validated classification of patients into one of the three levels of care, based on discriminant function scores, produced 75% correct classification; a 66% improvement over the percentage of correct classification likely by chance alone. Results support the construct validity of the PECS subscales and indicate they may be useful in validating clinically-based admission decisions among three of the levels of care promulgated by NARF. PMID- 1417464 TI - Predictors of family functioning one year following traumatic brain injury in children. AB - This study examined changes in family functioning and predictors of family outcome during the year following traumatic brain injury (TBI). The families of 94 children with TBI (mild = 50, moderate = 25, severe = 19), ages six to 15, were consecutively enrolled from two regional medical centers. Family interview ratings and standard measures of family and child functioning were completed three weeks after injury (measuring preinjury status), as well as three and 12 months. Two-thirds of families had moderate to good preinjury global functioning and coping resources, but more than half exhibited high levels of stress and at risk family relationships. No significant preinjury differences by injury severity were seen on any measure. Whereas few changes in family functioning were observed over the year in the mild or moderate groups, greater deterioration occurred in the severe group. From one third to one half noted moderate to severe strain in 13 problem areas often seen in individuals with TBI. Preinjury family global functioning, however, was more strongly predictive of 12-month family functioning (R2 = .38 to .68) than was injury severity (R2 = .05 to .09). In four out of five outcome areas assessed at 12 months, preinjury status in each area was the strongest single predictor. Preinjury coping was the best predictor of stress. Families at risk can be identified and need ongoing support for optimal functioning. PMID- 1417465 TI - Predicting return to work in traumatic brain injury using assessment scales. AB - This study compared two frequently used brain injury assessment scales with a comprehensive functional scale in their capability to predict return to work in a traumatic brain injured population. Fifty-seven consecutive admissions to an inpatient brain injury program were rated at admission and discharge using the following scales: Patient Evaluation and Conference System (PECS), Disability Rating Scale, and Levels of Cognitive Functioning Scale. Their relative accuracy in predicting return to work or school up to 26 months after the injury was assessed using hierarchical logistic regression analysis. In each analysis, return to work/school was the dependent variable. The independent variables were initial status and discharge status on each rating scale. Overall these scales predicted return to work with 73.5% to 84.4% accuracy. Total PECS and PECS Cognition scores were the most accurate predictors. Analysis of incorrect predictions revealed the importance of additionally tracking the social factors of substance abuse, family/community support and financial need to return to work. PMID- 1417467 TI - Communicating with families of rehabilitation patients about "do not resuscitate" decisions. AB - Resuscitation discussions can elicit potent emotional reactions from both health care providers and consumers. In rehabilitation settings, decision making grows more difficult if decisions must be sought from family members or proxies of incompetent patients. There is ample room for emotions and lack of clarity to lead to dissatisfaction and heightened distress. This paper outlines legal, ethical, and psychological factors that must be managed if clear communication between health care providers and families is to occur. Issues are discussed that can clarify thinking at each stage of the communication process. PMID- 1417466 TI - The treatment of agitation during initial hospitalization after traumatic brain injury. AB - Agitation after traumatic brain injury is disruptive for patient care, distressing, and difficult to treat. The use of propranolol has been advocated to control agitation after brain injury. It reportedly lacks some of the deleterious cognitive and emotional effects of other medications and physical restraints. This study was designed to test if propranolol is effective in reducing agitated behavior. Subjects had traumatic closed-head injury treated at a combined Level I Trauma Center and Rehabilitation Center. Twenty-one subjects met the criteria of agitation and were treated with propranolol or placebo in a double-blind fashion. The intensity of agitation was significantly lower in the treatment group although the number of episodes were similar. The use of restraints was also significantly lower in the treatment group. The results support the effectiveness of propranolol in reducing the intensity of agitation during the initial hospitalization after closed-head injury. PMID- 1417468 TI - Rehabilitation status in multiple handicap. AB - The Edinburgh Rehabilitation Status Scale (ERSS) was applied to 129 attenders at a day center for physical disability. All of the attenders had significant neurological impairment dating from birth or from infancy. Fifty-nine of the subjects (46%) had been diagnosed on conventional grounds as having mental handicap as well as physical disability. ERSS scores were compared with Barthel Index scores in all subjects and with PULSES profile in 50 subjects (27 physical disability alone, 23 combined with mental handicap). The ERSS scores clearly demonstrated significant differences in the level of disablement between the two groups in all four subscales as well as in total scores; the Barthel scores showed differences in self-care and total scores, and, to a lesser extent, in mobility. PULSES failed to differentiate the groups except in one of its subscales. The ERSS is a sensitive index of overall function and is useful in highlighting the additive effect of mental handicap and physical disability, a difference which may not be apparent when other assessment scales are used. PMID- 1417469 TI - Coronary risk in spinal cord injury: assessment following a multivariate approach. AB - A group of 96 men with spinal cord injury was studied to find out if patients with spinal cord injury were at an increased risk of coronary heart disease. A multivariate approach based on data produced by the Framingham study was used to estimate the probability of developing coronary artery disease within six years. Data obtained from the 96 patients were compared with data obtained from 96 nontrained, able-bodied men matched according to age. The results of this study suggest that patients with spinal cord injury show a risk of coronary artery disease similar to that estimated in non-trained, age-matched, able-bodied individuals. The risk increases with age, but it is of the same order as that found in the normal population and does not appear to be related to the duration of the disease. The results are inconclusive in regard to the level of the lesion as an independent factor of risk. PMID- 1417470 TI - Psychosocial adjustment of post-poliomyelitis ventilator assisted individuals. AB - The effect of severe disability, tracheostomy, and ventilator use on psychosocial functioning, gainful employment, life satisfaction, and perceived well-being were studied for a population of 395 ventilator assisted post-poliomyelitis individuals (PVAIs). Standard psychosocial survey instruments and other general questioning were used. Two-hundred-seventy-three physically intact health care professionals served as controls. They were surveyed about their own life satisfaction and perceived well-being and were asked to judge how severely disabled ventilator assisted individuals would respond to such questioning. The relative distress associated with ventilator use was also evaluated in a similar manner. Fifty six of 380 responding PVAIs (14.7%) expressed dissatisfaction with their lives in general. This compares with 8.5% of the controls and 7% of a previously studied general population. The controls significantly underestimated the patients' life satisfaction and well-being scores and significantly overestimated the relative hardship associated with ventilator use. The post polio individuals using noninvasive methods of assisted ventilation were also significantly more satisfied with their lives than were those ventilated via tracheostomy. Fifty-seven of 148 (39%) individuals married and 165 of 395 (42%) individuals were gainfully employed during long-term ventilator use. We conclude that many severely disabled post-poliomyelitis ventilator users lead productive lives. The vast majority have a positive affect and are satisfied with life. Noninvasive ventilatory support alternatives may lend to greater life satisfaction for these individuals than ventilation delivered via an indwelling tracheostomy. Health care professionals may significantly underestimate their patients' satisfaction with life and this may have a bearing on patient management. PMID- 1417471 TI - Attention and arousal: basic science aspects. AB - Disorders of attention are common after a variety of insults to the central nervous system. At present, treatment of these disorders is rarely based on a theoretical understanding of the neuroanatomy, neurophysiology, psychology, or psychopharmacology of attention. This article reviews the current state of knowledge of the mechanisms of attentional function and dysfunction, attempting to integrate findings across different types of research. In a subsequent article, the implications of these findings for clinical practice will be discussed. PMID- 1417472 TI - A patellar-tendon-bearing orthosis used in pediatric burn rehabilitation. AB - Burn rehabilitation in children presents a difficult challenge. Hypertrophic scar formation is accelerated in this population due primarily to the growth of normal surrounding tissue. Many patients who develop burn wound contractures of the foot and ankle are rendered nonambulatory. We describe a pediatric patients who developed fixed bilateral equinovarus deformities secondary to thermal injury. A patellar-tendon-bearing orthosis was fabricated for this patient to unload the foot-ankle complex with major weight bearing forces at the patellar tendon and tibial condyles. Through the incorporation of this orthosis with a full therapeutic rehabilitation program, the patient was able to ambulate independently using a rolling walker. We recommend the use of the patellar-tendon bearing orthosis for those pediatric burn victims who develop foot-ankle contractures to allow for ambulation until such time as additional, more aggressive treatment is tolerated, or on a more permanent basis, if necessary. PMID- 1417473 TI - Prenatal exposure to diethylstilbestrol (DES): childhood play behavior and adult gender-role behavior in women. AB - Data from lower mammals suggest a masculinizing or defeminizing influence of pre- or perinatal diethylstilbestrol (DES) exposure on various aspects of the sex dimorphic behavior (including juvenile rough-and-tumble play) of genetic females. However, three previous studies on childhood play and adult gender-role behavior in human females have led to ambiguous results. In a follow-up study of 60 women with prenatal exposure to DES and 26 controls, we used psychometrically well designed multi-item scales based on self-report inventories for the assessment of these aspects of behavior. No effects of DES could be demonstrated. We conclude that, at the doses studied, prenatal DES exposure in human females has not led to behavioral masculinization or defeminization of childhood play and adult gender role behavior. PMID- 1417474 TI - Partnership after induced abortion: a prospective controlled study. AB - To study the social and psychological consequences of induced abortion on the relationship between the pregnant woman and her partner, 92 patients seeking a socially indicated abortion, who had a stable partner at the time of abortion, were interviewed. Standardized psychological measures were used to assess their partnerships before abortion and on follow-up 1 year later. A control group of 92 patients (matched for age, marital status, duration of partnership, number of children, and educational background), drawn from a larger sample of women using safe contraceptive methods, completed the same psychological measures. Prior to abortion, partnerships in the study group showed considerably more conflicts and were less harmonious than in the control group. One year after the abortion, the number of separations in the study group was not significantly higher than in the control group, nor were there any remaining qualitative differences in the partnerships of either group. When separations occurred, they had been more frequently initiated by women in the study group than in the control group. PMID- 1417475 TI - Sexual and aggressive motives in sexually aggressive college males. AB - The relative contributions to sexual aggression of general sexual and aggressive motives and their respective inhibitory factors were compared. One hundred forty three university males responded to self-report measures of sexual and aggressive drives, sex and hostility guilt, social desirability response bias, and history of coercive sexuality. With the effects of social desirability controlled, the only predictor of sexual aggression was Sex Guilt, which predicted level of force used but not intimacy of the sexual act obtained. PMID- 1417476 TI - Do sex-linked behaviors in children influence relationships with their parents? AB - When relationships are found between parents' and children's behaviors it is usually assumed the parents' behaviors produced those of the children. Forty-four young adult males and 36 young adult females reported the degree to which they showed various sex-linked behaviors and feelings of same versus opposite sex identity in childhood, and adolescence, and currently. These behaviors accounted for up to 57% of the variance of measures of the quality of relationships with parents. In men, opposite-sex-linked behaviors and identity correlated most strongly with current negative parental and particularly paternal relationships. They also correlated strongly with negative paternal relationships in childhood. Some sex-linked behaviors and sex identity items in men correlated positively with maternal overprotection in childhood and adolescence. Correlations between women's sex-linked behaviors and sexual identity items and their parental relationships were weaker but more consistently negative. As in men, opposite-sex linked behaviors and identity in women correlated most strongly with current negative paternal relationships. The pattern of the associations and the finding that many opposite-sex-linked behaviors in subjects' childhood correlated most strongly with negative parental relationships in early adult life suggest that the parents' feelings could be partly a response to, rather than totally causal of, the subjects' sex-linked behaviors. PMID- 1417477 TI - Sustaining passion: eroticism and safe-sex talk. AB - It is axiomatic that communicating effectively is important for good sexual relations. In light of the AIDS epidemic and the necessity for safe-sex practices, the topic of caution and prevention is an emerging and critical discourse for the sexual encounter. Yet if this discourse is not to defy passion but rather complement it, then the study of sexual linguistics must be grounded within the realm of erotic reality. Three themes of eroticism and their implications for sexual interaction are explored in this paper: identity, context, and danger. Linguistic and relational constraints for enacting such a discourse are identified, accompanied by a critique of the treatment of erotic discourse in educational programs and the media. PMID- 1417478 TI - Statement of purpose. PMID- 1417479 TI - Normocalcemic hyperparathyroidism. Biochemical and symptom profiles before and after surgery. AB - Patients with normocalcemic hyperparathyroidism represent a diagnostic and therapeutic challenge. It is unclear to what extent these patients benefit from surgery in terms of correction of their serum chemistry abnormalities and their symptoms. We studied 142 patients: 23 with normocalcemic hyperparathyroidism (serum calcium levels below 2.62 mmol/L), 35 with intermittent hypercalcemia, and 84 with hypercalcemic hyperparathyroidism. Serum chemistry analyses and a standardized questionnaire of symptoms were completed before and after surgery. Overall, patients in the normocalcemic group reported a similar frequency of preoperative symptoms; had a similar reduction in postoperative symptoms; and had a similar normalization of serum calcium, parathormone, and phosphate levels as those in the two control groups. This study indicates that factors other than elevated serum calcium levels are in large part responsible for the symptoms of hyperparathyroidism and that these patients benefit from operation. PMID- 1417480 TI - Transhiatal esophagectomy for carcinoma of the esophagus and cardia. Experience with 160 cases. AB - We reviewed our experience from 1979 to 1990 with 160 cases of transhiatal esophagectomy for carcinoma of the lower esophagus and cardia to evaluate trends in patient selection, management, and outcome. Patients treated in the past 6 years (n = 110) and those treated before 1985 (n = 50) were similar in terms of age and sex distribution, medical history, and weight loss. The majority of tumors seen were adenocarcinoma, with patients in the latter group having significantly lower stages. Significant decreases in anesthetic time, units of blood transfusions, chest tube insertions, length of postoperative ventilation, incidence of postoperative pneumonia, and length of hospital stay were seen during the past 6 years. Wound infections increased significantly during the same period. The decrease in the 30-day mortality rate from 6% to 0.9% was not significant. Survival rates did not differ between groups, with overall rates of 62%, 40%, and 21% at 1, 2, and 5 years, respectively. PMID- 1417481 TI - An evaluation of two methods of limb salvage in extremity soft-tissue sarcomas. AB - Between 1983 and 1990, 38 sequential patients with stage II to III soft-tissue sarcoma of the extremities, as defined by the American Joint Committee on Cancer, were treated. Eighteen patients were treated with intra-arterial doxorubicin hydrochloride, limb salvage surgery, and radiation (group A). Twenty patients in group B were treated with cisplatin, isolated limb perfusion, limb salvage surgery, and radiation. The study was not randomized, but all patients were treated prospectively using one of the two protocols. The two groups were similar demographically and had similar lengths of survival without disease. There was only one local recurrence in the series, and this occurred in a group B patient who underwent perfusion with the lowest dose of cisplatin. Regional perfusion with either intra-arterial doxorubicin hydrochloride or cisplatin combined with limb salvage surgery and postoperative radiation are highly effective in preventing local recurrences and preserving functional extremities in patients with soft-tissue sarcoma. There was no difference in results between these two methods. PMID- 1417482 TI - Prospective trial of supranormal values as goals of resuscitation in severe trauma. AB - We prospectively tested the effect of the early postinjury attainment of supranormal values of cardiac index (> or = 4.52 L/min per square meter), oxygen delivery (> or = 670 mL/min per square meter), and oxygen consumption (> or = 166 mL/min per square meter) on outcome in traumatized patients with an estimated blood loss of 2000 mL or more. The goals in control patients were to attain normal values for all hemodynamic measurements. During the 6-month period, 33 protocol patients and 34 control patients with similar vital signs, estimated blood losses, and severity of injuries were enrolled in the study. Eight (24%) protocol patients died, while 15 (44%) control patients died. The protocol patients had fewer mean (+/- SEM) organ failures per patient (0.76 +/- 1.21 vs 1.59 +/- 1.60), shorter stays in the intensive care unit (5 +/- 3 vs 12 +/- 12), and fewer mean days requiring ventilation (4 +/- 3 vs 11 +/- 10) than did the control patients (P < .05 for each). We conclude that attaining supranormal circulatory values improves survival and decreases morbidity in the severely traumatized patient. PMID- 1417483 TI - Long-term results of treatment of Budd-Chiari syndrome with portal decompression. AB - Thirty-three patients with Budd-Chiari syndrome were studied for 1 to 19 years following portal decompression. All had ascites, hepatomegaly, abnormal liver function, angiographic demonstration of inferior vena cava and/or hepatic vein occlusion, and biopsy specimens showing intense hepatic congestion and necrosis. When thrombosis was confined to hepatic veins (20 patients), side-to-side portacaval shunt resulted in 95% operative survival, 90% prolonged survival, permanent shunt patency, relief of ascites, reversal of liver dysfunction, and reversal or improvement of hepatic lesions. When thrombosis involved the inferior vena cava, mesoatrial shunt (eight patients) was unsatisfactory because of a 63% mortality rate from liver failure due to shunt thrombosis. In contrast, a new procedure consisting of combined portacaval and caval-atrial shunts (five patients) has been highly successful, with 100% survival, shunt patency, relief of ascites, and reversal of pathologic abnormalities. PMID- 1417484 TI - Aortoenteric fistulas. AB - During an 11-year period ending in December 1991, 36 patients with aortoenteric fistulas were assessed and treated. Twenty-five patients (69%) had previously undergone aortic reconstruction with Dacron grafts, and 11 (31%) had spontaneous aortoenteric fistulas. Of the 25 patients with secondary fistulas, 14 (56%) had undergone aortic aneurysmal rupture or multiple aortic vascular reconstructions. Preoperative diagnosis was established in only 13 (36%) of 36 patients. Remote bypass preceding removal of the infected arterial prosthesis had the least morbidity and mortality. Three primary fistulas were found in unusual locations: aortocolonic, aortobronchial, and aortoesophageal. The patient with the aortoesophageal fistulas was the fifth survivor described in the literature. The overall mortality was 56%. A positive preoperative blood culture predicted a poor outcome. There were four amputations, there due to infection of the extra anatomical bypass. Prompt directed assessment to ensure appropriately staged operative intervention should improve survival. PMID- 1417485 TI - The ultrasonic dissector facilitates laparoscopic cholecystectomy. AB - The ultrasonic dissector disrupts tissues in proportion to their fluid content by ultrasonically induced cavitational forces. Since sturdy tissues are spared, the instrument tends to follow tissue planes and to dissect fat and other soft tissues selectively. We performed a prospective, randomized, controlled trial in 73 patients comparing the safety and efficacy of a prototype ultrasonic dissector with that of electrosurgery and laser during laparoscopic cholecystectomy. Randomization was as follows: ultrasonic dissector, 37 patients; electrosurgery, 21 patients; and laser, 15 patients. The results were not different with respect to patient characteristics, amount of blood loss, technical difficulties, length of hospital stay, or return to work. Subjectively, the ultrasonic dissector was thought to be of special value in isolating the hilar structures, particularly when they were edematous or embedded in fat. The ultrasonic dissector disintegrated the fat, which was rapidly cleared up the suction channel, allowing the cystic duct and artery to be bared with less risk of injury. We concluded that the ultrasonic dissector has unique attributes that contribute to the ease and safety of laparoscopic cholecystectomy. PMID- 1417486 TI - Protective effect of anisodamine on cultured bovine pulmonary endothelial cell injury induced by oxygen-free radicals. AB - Anisodamine, a Chinese traditional medicine herb, has been used for treatment of adult respiratory distress syndrome effectively, but little is known about its mechanism. We attempted to investigate if anisodamine could protect bovine pulmonary endothelial cell injury induced by exogenous oxygen-free radicals that were generated by xanthine/xanthine oxidase or opsonized zymosan-stimulated polymorphonuclear leukocytes. Results showed that with the addition of xanthine/xanthine oxidase into cultured bovine pulmonary endothelial cells, production of malondialdehyde and release of lactate dehydrogenase in supernatant increased, and synthesis of prostacyclin decreased. Damaged cellular membranes were revealed by scanning electron microscopy. The same was true for the addition of opsonized zymosan-stimulated polymorphonuclear leukocytes. While treatment with anisodamine greatly attenuated all of the above-mentioned parameters, results showed that (1) cultured bovine pulmonary endothelial cells could be damaged by oxygen-free radicals, (2) anisodamine had a protective effect on this injury as effective as that of superoxide dismutase and catalase, and (3) the membrane-stable action might contribute to the mechanism of protective effect against this injury. PMID- 1417487 TI - Is preoperative parenteral nutrition necessary for patients with predominantly ileal Crohn's disease? AB - We reviewed 46 consecutive patients with Crohn's disease predominantly affecting the ileum who specifically underwent right-sided ileocolectomy with primary anastomosis. All had a primary ileocolic anastomosis done by suture in a single layer closed fashion. Of these 46 patients, 19.6% had overt intra-abdominal sepsis, 30.4% had prior surgery, and 95.7% were taking corticosteroid drugs just before their operation. The mean (+/- SE) age was 31.5 +/- 2.0 years. The serum albumin level was less than 35 g/L in 93.5% of patients; all had a hematocrit value less than 0.36, and 80.4% lost more than 15% of their normal body weight. No patient received parenteral nutrition either preoperatively or postoperatively. No change in the preoperative, intraoperative, or postoperative approach to treating patients with predominantly ileal Crohn's disease occurred during the 10-year period of review. There was a 2.2% incidence of perioperative complications (one superficial wound infection) and a 6.5% incidence of late (>1.49 months) complications (two suture sinuses and one wound abscess unassociated with a fistula). Our findings suggest that preoperative parenteral nutrition is unnecessary in the majority of patients with predominantly ileal Crohn's disease specifically undergoing right-sided ileocolectomy and primary ileocolic anastomosis. PMID- 1417488 TI - Intraoperative irradiation in resected carcinoma of the pancreas and portal vein. AB - We developed a new method that provides a wide retroperitoneal irradiation field for patients with cancer of the pancreas in whom a long invaded portal vein is resected during intraoperative radiotherapy. This method involves the use of a venous bypass with a heparinized catheter that does not require systemic anticoagulation or a pump. Anastomosis is completed after intraoperative radiotherapy. Mean (+/- SD) duration of the venous bypass was 3.0 +/- 1.5 hours (range, 2.0 to 6.6 hours), during which no abnormalities of systemic blood pressure, heart rate, and electrocardiographic activity and no signs of congestion of the intestines were observed. Eleven patients were treated with this method, and no complications ascribed to intraoperative radiotherapy or venous bypass were found. We recommend this method as safe and simple for expanding the irradiation field for intraoperative radiotherapy in patients with pancreatic cancer in whom the portal vein is resected. PMID- 1417489 TI - Significance of wall thickness in symptomatic gallbladder disease. AB - One hundred cases of patients who underwent urgent cholecystectomy after presenting with symptoms of acute or subacute gallbladder disease were retrospectively reviewed. Sixty patients had pathologically proved acute cholecystitis, and 40 had chronic cholecystitis alone. One patient had an incidental gallbladder carcinoma, and four had global gangrene of the gallbladder. Focal ischemia, transmural hemorrhage, or focal necrosis (indicating more severe disease) was present in 19 patients. Fifty-four percent of patients had thin-walled gallbladders. Among patients with more severe acute disease, 56% had thin walls. Conversely, 24% of thin-walled gallbladders and 22% of thick walled gallbladders had evidence of focal necrosis or gangrene. We conclude that gallbladder wall thickness, although demonstrable on preoperative ultrasound examination in all patients, does not correlate directly with severity of disease or pathologic findings. PMID- 1417490 TI - Complement activation and polymorphonuclear neutrophil leukocyte elastase in sepsis. Correlation with severity of disease. AB - Complement activation is necessary for an adequate immune and inflammatory response to infections. Activation releases anaphylatoxins that cause vasodilation, increase vascular permeability, and trigger release of polymorphonuclear neutrophil leukocyte (PMN) lysosomal enzyme and oxygen radicals. Under normal circumstances, an orderly progression of such events has a beneficial antimicrobial effect. The same mechanism, however, when uncontrolled, may damage host tissues. To provide information about the clinical importance of such events in sepsis, different complement parameters (C3, C4, and the desarginated forms of C3a [C3a(des)-Arg] and C5a [C5a(des)-Arg]), PMN elastase, and malondialdehyde (a by-product of membrane peroxidation by oxygen radicals) were measured daily in 26 septic patients and correlated with two objectively assessed and previously validated severity scores (acute physiology and chronic health evaluation [APACHE II] and Sepsis Severity Score [SSS]). Nonsurvivors (n = 12) had significantly greater and longer lasting complement activation than that in survivors, as reflected by higher levels of catabolic peptides (C3a(des)-Arg) and lower levels of native proteins (C3 and C4). C3a(des)-Arg, C3, C4, and the C3a(des)-Arg-C3 ratio were correlated with Sepsis Severity Scores. Polymorphonuclear neutrophil leukocyte elastase levels were higher in nonsurvivors and were correlated with C3a(des)-Arg and the C3a(des)-Arg-C3 ratio. Malondialdehyde levels were significantly higher in all patients than in controls, without, however, any relationship to severity of disease or clinical outcome. Since the higher and more persistent the complement activation and polymorphonuclear neutrophil leukocyte stimulation, the worse the patient's prognosis, we conclude that these mechanisms may be important in the clinical development of sepsis. PMID- 1417491 TI - Pancreatic complications following cardiopulmonary bypass. Factors influencing mortality. AB - Pancreatic complications following cardiopulmonary bypass are infrequent but are associated with high mortality. All cases of pancreatic complications following cardiopulmonary bypass from 1972 to 1987 at a single institution were retrospectively reviewed. Of 5621 patients who underwent cardiopulmonary bypass, 25 (0.44%) sustained pancreatic complications. There were 15 cases of acute pancreatitis and 10 cases of pancreatic necrosis, with 11 deaths in the group reviewed, a mortality rate of 44%. Factors that were correlated with mortality associated with pancreatic complications in this study include preoperative hypotension, preoperative use of inotropic agents, and renal failure (preoperative and postoperative). Factors that have been previously associated with mortality from pancreatic complications in other studies, such as fluid sequestration, respiratory failure, sepsis, tachycardia, hypocalcemia, age greater than 55 years, and abnormal laboratory findings, were not found to be significantly associated with mortality in this study. Of the five patients for whom complete data were available, not one patient received greater than 800 mg of calcium per square meter of body surface area in the perioperative period. While the exact mechanism of pancreatic injury remains unclear, based on experimental studies and clinical correlation, it is likely that pancreatic ischemia remains a significant contributing factor. We conclude that no factor specifically associated with cardiopulmonary bypass was correlated significantly with mortality. PMID- 1417492 TI - A randomized clinical trial comparing two methods of fascia closure following midline laparotomy. AB - Three hundred forty women undergoing midline laparotomy were randomized into an interrupted suture (polyglactin 910, size 1) or a continuous suture (polyglyconate, size 0) closure group. The two groups were well balanced with respect to various risk factors for postoperative wound complications. Early evaluation revealed no differences between the continuous and interrupted suture groups with respect to wound infection (3% vs 1%), superficial wound dehiscence (2% vs 4%), and deep wound dehiscence (0.6% vs 0%). Late evaluation showed no differences between the two groups either. Continuous polyglyconate and interrupted polyglactin 910 sutures had a similar incidence of suture fistula (0% vs 2%), wound pain (1% vs 2%), and incisional hernia (3% vs 4%). Continuous closure was done faster and resulted in less foreign-body suture material. Despite its smaller diameter, the polyglyconate suture also retains a higher tensile strength after surgery than does the quicker-degrading polyglactin 910 suture. Results of this study lead to the conclusion that a running polyglyconate suture is the better choice for closure of the abdominal-wall fascia following midline laparotomy. PMID- 1417493 TI - Racial differences in the anatomical distribution of colon cancer. AB - The objective of this study was to determine whether racial differences exist with regard to the anatomical distribution of adenocarcinoma of the colon. We conducted a retrospective study of consecutive patients with primary colon cancer seen during a 12-year period (1976 to 1987) identified by the Rush Tumor Registry. The setting was a large, tertiary-care, private medical center, located in the inner city of Chicago, Ill. A chi 2 unpaired Student's t test of association was performed to detect any statistically significant difference in the anatomical sites of distribution between blacks and whites. A statistically significant percentage of black patients had proximally located primary colon lesions compared with white patients. This observation was independent of the actual anatomical definition of right-sided or proximal colon lesions. These findings suggest that a significant percentage of black and white patients are less likely to be diagnosed with colon cancer at a more curable stage, when abiding by the current screening guidelines of the American Cancer Society and the National Cancer Institute. The impact is greater on black patients with adenocarcinoma of the colon. PMID- 1417494 TI - Repair of parastomal hernias using polypropylene mesh. AB - Parastomal hernias are a common complication of ostomy construction. We have developed a method of repair that uses two strips of polypropylene prosthetic mesh through a midline incision. The medical records of 19 patients who underwent parastomal hernia repair were retrospectively reviewed. All nine patients operated on for this condition by the senior author (R.G.P.) (group 1) underwent repairs with this technique. All ten patients operated on by other surgeons in our center (group 2) underwent repairs in which the stoma was moved, the fascia was directly repaired through a parastomal incision, or the fascia was repaired via a midline incision. No patients in group 1 had recurrences while five patients in group 2 had recurrences. Neither group developed strictures or stomal prolapse. Our method of repair is technically easy and has excellent results. It is especially suitable in very large hernias in which incisional hernia is likely in the original stoma site if the stoma is moved. PMID- 1417495 TI - Ischemic stricture and perforation. An unusual complication after successful barium reduction of an intussusception. AB - Intussusception is a common cause of intestinal obstruction in infants. Use of a barium enema affords both diagnostic confirmation and a chance for nonsurgical reduction of the intussusception. While failed hydrostatic reduction is an indication for surgical intervention, delayed complications of hydrostatic reduction have not been described. We present a case of ischemic stricture and perforation developing after the successful reduction of an intussusception. PMID- 1417497 TI - Diagnostic laparoscopy: is it being overused? PMID- 1417496 TI - Tubular adenoma of the main pancreatic duct. AB - We report a case of tubular adenoma of the duct of Wirsung with focal villous changes. To our knowledge, this is the 13th reported case of this uncommon neoplasm and the first with a primarily tubular histologic pattern. The patient presented with abdominal pain and diarrhea and was found on endoscopic retrograde cholangiopancreaticography to have a mass in the head of the pancreas, which was confirmed by endoscopic ultrasound. Clinical and pathological features of the 12 previously reported cases are reviewed. Intraoperative testing failed to rule out adenocarcinoma which, in addition to difficulties presented by local anatomic relationships of the tumor, supports wide surgical resection as the preferred surgical solution. PMID- 1417498 TI - [The 42nd General Meeting of the Japanese Society of Allergology. Sendai, Japan, October 28-30, 1992. Abstracts]. PMID- 1417499 TI - [Interindividual differences in personality and behavior and subjective health problems in shift workers]. AB - A total of 604 experienced shift workers were administered a battery of questionnaires in order to examine the relationships between the shift workers' features and subjective health complaints taken as signs of intolerance to shift work. The individual difference measures included: hard-driving and competitiveness, speed and impatience, relaxed, efficiency, flexibility of behaviour, evening, rigidity of sleeping habits, vigorous, languidness, inveterate, flexibility of habits, neuroticism, extraversion, lie-scale, age and work experience. The subjective health complaints included: generally poor health, musculo-skeletal, respiratory and psychosomatic-digestive complaints, and digestive problems. Correlation and multiple regression analyses showed that in workers some personality features and patterns of behaviour were related to the subjective health complaints. More health complaints were placed by workers who were emotionally unstable, less relaxed, inefficient, rigid (e.g. unable to control the behavioral arousal level), hard-driving and competitive, speedy and impatient (A-types), rigid in sleeping and other life habits, languid, older and with longer shift work experience. PMID- 1417500 TI - [Levels and profiles of polycyclic aromatic hydrocarbons in Zenica in relation to the seasons]. AB - Twelve polycyclic aromatic hydrocarbons were measured in samples of airborne particles collected in the town of Zenica in the Republic of Bosnia and Herzegovina every third or fourth day throughout the year. The concentrations were especially high in winter when in addition to permanent industrial emissions those from individual heating systems were also present and when owing to climatic and orographical circumstances temperature inversions occurred more frequently. The profiles of polycyclic aromatic hydrocarbons i.e. their ratios to benzo-a-pyrene did not demonstrate great seasonal variations with the exception of fluoranthene and pyrene. The mean annual concentrations (winter to summer concentration ratios) were higher than in the areas where there was no permanent source of emissions. PMID- 1417501 TI - [Respiratory symptoms and pulmonary ventilating capacity in professional drivers and mechanics]. AB - The prevalence of respiratory symptoms and ventilatory capacity were studied in 116 drives and 119 mechanics. The drivers and mechanics demonstrated a significantly higher prevalence of most chronic respiratory symptoms than control workers. Among drivers smokers there was a significantly higher prevalence of most chronic respiratory symptoms than among non-smoking drivers. Drivers and mechanics with more than 10 years of service also showed a higher prevalence of respiratory symptoms than those employed for less than 10 years. A certain number of subjects complained of acute symptoms during work shift. All ventilatory capacity tests, particularly FEF25, demonstrated lower values in comparison to predicted normal values. Our data for drivers and mechanics indicate that long term employment, particularly in combination with smoking, may cause the development of respiratory symptoms and changes in lung function. PMID- 1417502 TI - [The position and role of occupational medicine and specific health care of workers]. AB - Specific care for workers' health has been largely deficient during the past decade, despite the existing legislation. Consequently, the protection of workers' health has been seriously endangered, with the resultant long-term damage. The main reasons for this were the absence of clearly defined responsibilities regarding the financing and execution of the specific health care measures as well as lack of penalty for their non-implementation. As a result, there was indifference on the part of enterprises, indifference and inadequate organization of occupational health services as executors of the specific health care measures, and indulgence on the part of the court, inspecting services and other competent bodies. The situation could be helped only if a completely different approach, suited to the market economy, were adopted. The State should prescribe only the general rules, while the carrying out of specific health care should, with rare exceptions, be left to the interested parties, enterprises in the first place, and to the law of supply and demand. Naturally, such approach can be successful only in the legal State where the ownership of enterprises and professional services is strictly defined and the court and inspection services are free to act independently. Only then will the responsibility of the owners in respect to the breaking of rules, impairing workers' health and unprofessional work of health and other personnel be raised to an appropriately high level. In such an environment the place and role of occupational health activity as well as its name are bound to see a radical change. PMID- 1417503 TI - [Evaluation of the quality of life of disabled workers based on the most frequently used type of health care]. AB - An investigation was conducted among the dock workers from the port of Rijeka, where disabled workers made 13.1% of the total number of the employed. The most common causes of disablement were musculo-skeletal and connective tissue diseases (27%), injuries (20%) and diseases of the nervous and circulatory systems (13%). Chronic diseases in these workers whose mean age was 43.8 years were twice as frequent as in other workers (mean age 39.7 years). The average working span of disabled workers was 12.2 years, compared to 8.9 years of the rest of the working population. Analysis showed that in the year after disability assessment, workers with reduced working capacity visited their physicians 2.1 and specialists 1.7 times less often than the other workers. In general, the rate of absenteeism in the year following the assessment of disability was reduced 3.5 times. All the differences were very significant, (P < 0.01). Results lead to the conclusion that medical and social rehabilitation of disabled workers as well as their integration into the working environment were very successful, which undoubtedly had a positive impact on the quality of their life. PMID- 1417504 TI - [Recommendations in relation to shift work]. AB - The purpose of the recommendations is to decrease as much as possible physiological, psychological and social problems connected with shift work. To achieve this goal working hours should be organized to take account of shift workers' tolerance to shift work. When recruiting new shift workers certain personal characteristics that make work in any shift work system inadvisable should be checked. As shift work can be considered to be an additional load, shift workers' health requires regular checking-up. If there are signs of health impairment, the workers should be removed from night shift work permanently or at least temporarily. The shift workers' free time should be arranged so as to facilitate recovery from shift work, especially after night shift. To decrease the workload during the night shift, if possible, workers should be given opportunity to take naps during work. PMID- 1417505 TI - [The effect of aluminum on human health]. AB - The paper aims at reviewing recent knowledge of the pathophysiological mechanisms involved in aluminium poisoning which is often manifested as anaemia, osteopathy and encephalopathy. In order to clarify the mechanisms of aluminium toxicity its metabolism and ways of human exposure are also described. The immunosuppressive effect as well as certain anticarcinogenic effects of aluminium are still insufficiently well known. It is pointed out that different chemical elements can exert a protective action during aluminium poisoning. PMID- 1417506 TI - Myotonia fluctuans. PMID- 1417507 TI - Cognitive function in late Lyme borreliosis. PMID- 1417508 TI - Regional cerebral oxygen consumption, blood flow, and blood volume in healthy human aging. AB - Using high-resolution positron emission tomography and the oxygen 15 continuous inhalation method, we examined the changes in cerebral metabolic rate of oxygen, blood flow, blood volume, and oxygen extraction fraction as a function of age in 25 optimally healthy, unmedicated volunteers who ranged in age from 20 to 68 years. Subjects were strictly selected for absence of cerebrovascular risk factors, dementia, or mental disorders; they had neither biological nor clinical abnormalities, and no focal anomaly on computed tomographic scan. Regions of interest were determined according to the anatomical structures defined on corresponding computed tomographic scan cuts obtained using a stereotaxic head positioning method. This same method was also used for positron emission tomographic imaging. There was no significant effect of aging on PaCO2 values, hematocrit, arterial blood pressure, cholesterol and triglyceride levels, and blood glucose levels. In most cerebral cortex gyri, the cerebral metabolic rate of oxygen significantly decreased with age according to a linear pattern, with the same magnitude (about -6% per decade) in all four lobes and on both sides. This effect of age on cortical cerebral metabolic rate of oxygen persisted when the possible influence of cortical atrophy, gender, and head size were partialled out. In contrast, the white matter, deep gray nuclei, thalamus, and cerebellum were not significantly affected. The cerebral blood volume declined with a similar pattern to cerebral metabolic rate of oxygen, while changes in cerebral blood flow were less significant, presumably because of larger variance of data across subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417509 TI - Neurocognitive effects of aluminum. AB - The neurocognitive effects of aluminum (Al) were studied in 35 hemodialysis patients. Higher Al levels were associated with a decline in visual memory. As Al levels increased, patients with lower vocabulary scores (a measure of premorbid intelligence) showed a decline in attention/concentration, frontal lobe functions, and on several neurocognitive measures, while those with higher vocabulary scores revealed no Al-related decline. These results suggest that individuals with lower verbal intelligence may possess less well-developed compensatory strategies to overcome the neurocognitive effects associated with Al. These data also indicate that Al is neurotoxic and, therefore, potential sources of environmental Al should be identified and eliminated. PMID- 1417510 TI - Parietal pseudothalamic pain syndrome. Clinical features and anatomic correlates. AB - We studied six patients who developed spontaneous hemibody pain following lesions of the parietal lobe. The pain was characterized as burning or icelike, and was associated with impairment of pin and temperature appreciation. Computed tomographic scanning showed that the common area of involvement in all cases was the white matter deep to both the caudal insula and the opercular region of the posterior parietal cortex. We suggest that disruption of the interconnections between these cerebral cortical areas (including the second somatosensory representation, SII) and the thalamus, particularly the intralaminar and ventroposterior nuclei, may be responsible for producing a thalamocortical disconnection syndrome with spontaneous pain as its clinical manifestation. PMID- 1417511 TI - Neurologic signs in Alzheimer's disease. Results of a prospective clinical and neuropathologic study. AB - Neurologic signs and their neuropathologic correlates were examined in a sample of 56 patients with autopsy-proved Alzheimer's disease (13 men, 43 women; mean age at death, 83.1 years; range, 67 to 96 years) from a prospective longitudinal study. Full-range regular rigidity with cog-wheeling was found in 20 patients and was significantly associated with lower neuron counts in the substantia nigra and with the presence of Lewy bodies in the brain stem and neocortex. Twelve patients with myoclonus had a younger age at onset, a lower age at death (mean, 78.6 years), and lower neuron counts in the serotoninergic dorsal raphe nucleus and in the noradrenergic locus coeruleus than did the patients without myoclonus. Generalized motor seizures were reported in six patients, and they had significantly lower counts of pyramidal cells in cortical layers III through IV of the parietal cortex (area 7) and slightly decreased pyramidal cell numbers in the parahippocampal gyrus (area 28). The 19 patients with a positive grasp reflex had an earlier onset of illness and a significantly inferior performance on the Mini-Mental State examination and Cambridge Cognitive Examination tests. They, and 25 patients with a positive snout reflex, had significantly lower counts of large pyramidal cells in layers III through V of the frontal cortex (area 32). These results indicate that different neurologic symptoms in Alzheimer's disease can be related to disproportionate neuronal degeneration in functionally different brain areas. PMID- 1417512 TI - Matching-to-sample deficits in patients with senile dementias of the Alzheimer and Lewy body types. AB - Using a computerized matching-to-sample task, nonverbal visual recognition memory was studied in two groups of patients suffering from senile dementia of the Alzheimer type or the recently described senile dementia of the Lewy body type. The patients' cognitive abilities had been shown to be similar according to a number of standard psychometric tests. The two groups did not differ with respect to simultaneous matching-to-sample performance, although both were impaired relative to control. The group with senile dementia of the Lewy body type was severely impaired, relative to the group with senile dementia of the Alzheimer type, when delays (delayed matching to sample) were introduced. The findings suggest that short-term mnemonic processes, mediated by temporal lobe structures, could be more severely affected in senile dementia of the Lewy body type. PMID- 1417513 TI - Contributions of the left intralaminar and medial thalamic nuclei to memory. Comparisons and report of a case. AB - A patient complained of memory disturbance after a small left thalamic infarction. Neuropsychological testing revealed her memory to be normal provided that she was allowed to rehearse or use semantic encoding strategies. When these strategies were prevented, her performance was impaired. Mapping of the lesion demonstrated involvement of the caudal intralaminar nuclei (centre median and parafascicular nuclei), and portions of the medial nuclei (medioventral [reuniens], centromedial, and the most inferior aspect of the mediodorsal nucleus). The majority of mediodorsal nucleus, the mammillary bodies, the mammillothalamic tract, and the anterior thalamic nuclei, were spared. A comparison among our patient's performances and those of alcoholic Korsakoff patients, patient NA, and amnestic patients with circumscribed diencephalic lesions suggests that there are two distinct behavioral and anatomic types of memory impairment associated with diencephalic lesions. The severe amnesia associated with damage to the mammillary bodies, midline nuclei, mammillothalamic tract, and/or dorsomedial nucleus of the thalamus (eg, Korsakoff and NA) is characterized by encoding deficits that never approximate normal performance. The memory disturbance associated with damage to the intralaminar and medial nuclei of the thalamus is milder and is characterized by severe distractibility. PMID- 1417514 TI - Gist recall in multiple sclerosis. AB - This study examined gist recall (memory for important story ideas) in patients with multiple sclerosis. Twelve patients with clinically probable or definite multiple sclerosis and 10 neurologically intact control subjects were read prose passages from the Wechsler Memory Scale-Revised Logical Memory subtest. The idea units from these passages contained low, medium, and high information content to the stories. In comparison with the control subjects, the patients recalled fewer total elements over immediate and delayed conditions. However, similar to controls, they recalled more ideas that were of high rather than low or medium importance. These results suggest that semantic sensitivity to important ideas of narratives is a relatively preserved feature in multiple sclerosis. PMID- 1417515 TI - Humoral and cellular immunologic study of cerebrospinal fluid in a patient with Behcet encephalitis. AB - To study the immunopathogenesis of neuro-Behcet syndrome, we performed serial cerebrospinal fluid (CSF) examinations in a patient with Behcet's syndrome and involvement of the central nervous system. Before and after immunosuppressive treatment, we measured the CSF indexes of immunoglobulins (Ig), and the third (C3) and the fourth (C4) component of complement, and quantified immune complexes and lymphocyte subsets in CSF and peripheral blood. During active encephalitis, humoral abnormalities were intrathecal production of IgM and, to a lesser degree, IgG and IgA, presence of immune complexes in CSF but not in peripheral blood, intrathecal C3 production, and elevated CSF C3 and C4 concentrations; lymphocyte subset analysis showed an increased CSF CD8+ T-cell percentage, in combination with slightly increased PB CD3+ and CD8+ T-cell subsets. After effective immunosuppressive treatment, humoral and cellular CSF values were normal. We conclude that intrathecally produced immunoglobulins, immune complexes, and C3 as well as CD8+ T cells are likely to participate in the development of Behcet encephalitis. PMID- 1417516 TI - Central nervous system involvement in the eosinophilia-myalgia syndrome. AB - A patient with eosinophilia-myalgia syndrome developed progressive central nervosa system involvement that did not improve despite discontinuation of L tryptophan therapy. Neurologic impairment was manifested initially by spastic monoparesis, which was improved by treatment with methyl-prednisolone and hydroxyurea. Recurrence of weakness was accompanied by gait ataxia, dysphagia, and complaints of a gradual decline in memory and concentration. Neuropsychological testing identified a broad pattern of cognitive deficits suggestive of a subcortical dementia, and magnetic resonance imaging demonstrated multiple high-signal lesions in the white matter. Cognitive deficits appear to be underrecognized in patients with the eosinophilia-myalgia syndrome. The response of our patient's initial symptoms to corticosteroid therapy suggests a possible role for autoimmune mechanisms in the pathogenesis of central nervous system involvement in the eosinophilia-myalgia syndrome. Neuropsychological evaluation should be performed in patients with cognitive complaints to delineate the full spectrum of central nervous system impairment associated with the eosinophilia myalgia syndrome. PMID- 1417517 TI - Longitudinal neurophysiologic studies in a patient with metachromatic leukodystrophy following bone marrow transplantation. AB - We describe a girl with late infantile metachromatic leukodystrophy. The patient has been followed up with serial neurologic and neurophysiologic examinations for 8 years following bone marrow transplantation, which she underwent when she was 4 3/4 years old. Her older sister died from metachromatic leukodystrophy at the age of 8 years, whereas our patient has retained significant cognitive and motor skills. Serial neurophysiologic studies initially demonstrated continued deterioration after the bone marrow transplantation, but since then, most results have remained stable or improved. Although, to our knowledge, there have been no previous serial studies of metachromatic leukodystrophy, individual case studies suggest that these findings in our patient are very unusual. With the advent of possible treatment for this condition, there is a need for further serial neurophysiologic studies to characterize the natural progression and the possible detection of progression or reversal with treatment. PMID- 1417518 TI - The importance of visual feedback on the accuracy of jaw and finger positioning in man. AB - The anatomical position of the mandible means that direct visual feedback is not possible. To clarify the role of visual information, several jaw- and finger positioning tasks were designed, both in a 'free-movement' and an 'isolated' (arm or head fixed) state, with or without a visual feedback display of the target position. The subjects had to position the mandible or the index finger of the preferred hand on to a movable metal bar and to maintain a defined position coinciding with the target level provided on an oscilloscope screen. The position signal was tape recorded and computer analysed off-line. Digital filtering differentiated between the drift and the oscillations around the target (root mean square). The results demonstrated a lack of precision in the free-movement, finger-positioning task after withdrawal of visual feedback. For jaw opening and closing muscles, position control was less impaired when a visual feedback display was abolished. It was suggested that the efficiency of jaw positioning is not primarily determined by visual feedback. PMID- 1417519 TI - Mathematical definition of the curve of Spee in permanent healthy dentitions in man. AB - The intrinsic morphology of the mandibular curve of Spee (i.e. independent from reference planes) was studied in 50 men and 45 women with sound dentitions. Left and right curves were reconstructed by a second-order quadratic interpolation of buccal cusp tips. Gender differences were found in both sides, while side differences were found only in the male sample. Male and female curves had similar concavities, but the position of the interpolating second-order quadratic curve relative to the dental arch was significantly different. The right and left male sides showed different concavities, the right-hand side being flatter than the left. Male curves appeared larger than female ones, and the left-hand side was significantly larger than the right regardless of gender. The reported second order quadratic curves could be used as reference for prosthetic and orthodontic reconstructions. PMID- 1417520 TI - Changes in protein kinase C activity in rat calvarial bone cells cultured in a low-calcium environment. AB - This enzyme activity was examined in bone cells cultured for 8-10 days; the calcium concentration was 1.87 +/- 0.05 (n = 10) mM in the control medium and 0.34 +/- 0.02 (n = 10) mM in the low-calcium medium. The activity was significantly lower in the low-calcium group than in the control (p less than 0.01). The cytosolic fraction decreased more than the membranous fraction. After restoration to a regular calcium environment, the protein kinase C activity recovered rapidly to near the control value. The extent of recovery was greater in the membranous than in the cytosolic fraction. These results suggest that the enzyme was inhibited in bone cells placed in a low-calcium environment, while the sensitivity in the membrane was enhanced. PMID- 1417521 TI - Serum antibody responses in human periodontitis to cellular components of Capnocytophaga. AB - Serum levels of IgM, IgG and IgG-antibody subclasses directed against cell envelopes, lipopolysaccharides and cytoplasmic fractions from Capnocytophaga sputigena, C. gingivalis and C. ochracea were examined in age-, race- and sex matched periodontally healthy (n = 25) subjects and subjects with adult periodontitis (n = 25). The envelopes and cytoplasmic fractions were obtained by ballistic disintegration of the cells and ultracentrifugation. Cell envelopes were treated with DNase, RNase and lysozyme. Lipopolysaccharides were obtained by hot phenol-water extraction and treated with DNase and RNase. The relative levels of the antibodies in response to the cell fractions were measured by the streptavidinbiotin micro enzyme-linked immunosorbent assay. Both groups showed IgM and IgG antibodies to each fraction of the three Capnocytophaga species, but the frequency of positive IgG subclass responses varied. The IgG4 responses were lower than the other subclasses. There were no significant differences between the IgM antibody levels of the two groups. However, the adult periodontitis group had significantly lower IgG antibody titres to the cell envelopes and cytoplasmic fractions of C. gingivalis and C. ochracea, and lipopolysaccharide of C. gingivalis. These results were reflected in the depressed levels of IgG1 and/or IgG2 to these cellular fractions from the same bacterial species. The adult periodontitis group also showed a lower level of IgG1 to the cytoplasmic fractions of C. sputigena without any depression in the total IgG antibody level. There were no significant differences between the groups in IgG3 and IgG4 antibody levels to any of the cellular fractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417522 TI - The effect of dietary factors on intradentinal dye penetration in the rat. AB - Fluorescent dye injected systemically into rats penetrated the dentinal tubules of molar teeth in a dynamic fashion. The presence of dye was established using histological and fluorescence microscopy techniques. The rate of intradentinal dye penetration was dependent on dietary factors: it was high in rats chronically fed Purina rat chow and low in rats fed a cariogenic, high-sucrose diet. In addition, parotidectomized rats showed low levels of intradentinal dye penetration, even though they were maintained on Purina chow. One and 2 ml of plasma from Purina-fed rats were effective in stimulating the dye penetration in intact and parotidectomized rats, whereas 2 and 4 ml of plasma from rats fed a high-sucrose diet were ineffective when infused in either intact or parotidectomized animals. The results suggest that rats fed Purina chow have a significantly higher titre of a circulating, dye penetration stimulating factor than animals fed a high sucrose diet. This circulating factor could be the equivalent of the parotid hormone isolated from porcine tissue. It is suggested that dietary factors may affect secretion of a parotid hormone and thereby regulate the rate of dentinal fluid movement. There is therefore the prospect of a functional relationship between diet, the regulation of dentinal fluid flow by an endocrine system and dental health. PMID- 1417523 TI - Stimulation by interleukin-1 of interleukin-6 production by human periodontal ligament cells. AB - Interleukin-1(IL-1), a cytokine present in the gingiva and crevicular fluid of patients with periodontitis and in the periodontal ligament (PDL) of experimentally moved teeth, has multiple biological activities, including the ability to elicit bone resorption. Interleukin-6, also found in the gingiva of patients with periodontitis, may induce osteoclastic bone resorption through an effect on osteoclastogenesis. Here IL-6 production and its gene expression in response to recombinant IL-1 beta were examined in primary cultures of PDL cells. IL-1 beta stimulated IL-6 production by these cells in a dose- and time-dependent manner; this increase in IL-6 production was much higher than that in human gingival fibroblasts. In situ hybridization, using a synthetic oligonucleotide DNA probe of the IL-6 gene, revealed that most PDL cells expressed IL-6 mRNA in response to IL-1 beta treatment. The finding that IL-6 is produced by PDL cells and is regulated by IL-1 beta has revealed a potentially important mechanism for controlling alveolar bone resorption. PMID- 1417524 TI - Plasminogen activators in normal and malignant oral epithelium in vivo and in vitro. AB - Urokinase-type (uPA) and tissue-type (tPA) plasminogen activators were identified by fibrinolytic autography in the sulcus epithelium of human gingival mucosa but not in the orthokeratinized gingival epithelium. Fibrinolytic activity was present only over blood vessels in frozen sections of oral squamous cell carcinomas, the malignant epithelial cells showing no plasminogen activator activity. Plasminogen activators could not be demonstrated in either the sulcus or gingival epithelium by immunofluorescence, but both uPA and tPA were found in occasional squamous carcinoma cells. Fibrinolytic activity of culture fluids from epithelial explants grown in vitro from human gingival mucosa showed marked variation, but activity was much higher in the culture supernatants than in the cell lysates. Fibrinolytic activity of culture fluids from epithelial explants of squamous cell carcinomas was low both in supernatants and lysates. Zymogram overlays of sodium dodecyl sulphate-polyacrylamide electrophoretic gels from culture supernatants showed that the low fibrinolytic activity of culture supernatants of oral squamous cell carcinomas was due to the associated presence of plasminogen activator inhibitors. The fibrinolytic activity in the zymogram was due predominantly to uPA but some lysis was due also to tPA. PMID- 1417525 TI - Changes in the lectin-binding of capillaries in rat salivary glands after streptozotocin-induced diabetes. AB - The lectin-horseradish peroxidase conjugate of GSA I-B4 (Griffonia simplicifolia isolectin) has some binding affinity with capillary walls in sections of the major salivary glands from normal rats. After inducing diabetes with streptozotocin a conspicuous increase in the staining intensity with GSA I-B4 was already evident in parotid capillaries at 3 weeks and this increase persisted at 3 and 6 months. In submandibular capillaries, however, an increased uptake of GSA I-B4 was evident only at 6 months after inducing diabetes. The reasons for these different time scales in the two glands are not known but the increased uptake of GSA I-B4, which is due to an increase in carbohydrate-containing sites with available terminal alpha-D-galactose, is considered to reflect a pathological change. PMID- 1417526 TI - Optic neuritis or anterior ischemic optic neuropathy? PMID- 1417527 TI - Peribulbar injection and direct infiltration for vitreoretinal surgery. PMID- 1417528 TI - Solitary hypopigmented nevus of the retinal pigment epithelium in the macula. PMID- 1417529 TI - Conjunctival prolapse following craniofacial surgery. PMID- 1417530 TI - Treatment of a massive orbital-capillary hemangioma with interferon alfa-2b: short-term results. PMID- 1417531 TI - Spontaneous peeling of an idiopathic epiretinal membrane in a young patient. PMID- 1417532 TI - Brown's superior oblique tendon syndrome after Baerveldt glaucoma implant. PMID- 1417533 TI - Fat adherence simulating inferior oblique palsy following blepharoplasty. PMID- 1417535 TI - The importance of temporal artery biopsy in the diagnosis of giant cell arteritis. PMID- 1417534 TI - Physicians are using practice parameters. PMID- 1417536 TI - Making sense of keratospeak. IV. Classification of refractive surgery, 1992. PMID- 1417537 TI - The collaborative corneal transplantation studies (CCTS). Effectiveness of histocompatibility matching in high-risk corneal transplantation. The Collaborative Corneal Transplantation Studies Research Group. AB - The Collaborative Corneal Transplantation Studies (CCTS) were designed to evaluate the effect of donor-recipient histocompatibility matching and crossmatching on the survival of corneal transplants in high-risk patients. Corneas were allocated to the 419 patients in the double-masked Antigen Matching Study on the basis of serologically defined HLA-A, -B and HLA-DR antigen match. ABO blood group compatibility was determined but not used for recipient selection. The 37 patients in the Crossmatch Study were randomly assigned to receive a cornea from either a positively or negatively crossmatched donor. All patients received topical steroid therapy according to a standard protocol. Matching for HLA-A, -B and HLA-DR antigens had no effect on overall graft survival, the incidence of irreversible rejection, or the incidence of rejection episodes. At 3 years after surgery, the estimated proportion of eyes with graft failure was 41% for the ABO-incompatible group and 31% for the ABO-compatible group (relative risk, 1.43; 95% confidence interval, 1.00 to 2.06). The estimated proportion of eyes with failure from rejection by 3 years was 30% for the ABO incompatible group and 16% for the ABO-compatible group (relative risk, 1.98; 95% confidence interval, 1.25 to 3.13). The positive group in the Crossmatch Study had fewer graft failures, rejection failures, and rejection episodes than the negative group; however, these differences were not statistically significant. These studies demonstrate that, for high-risk patients who are immunosuppressed by topical steroid therapy and followed up according to the CCTS protocol: (1) neither HLA-A, -B nor HLA-DR antigen matching substantially reduces the likelihood of corneal graft failure; (2) a positive donor-recipient crossmatch does not dramatically increase the risk of corneal graft failure; and (3) ABO blood group matching, which can be achieved with relatively little effort and expense, may be effective in reducing the risk of graft failure. PMID- 1417539 TI - Changing trends in the indications for penetrating keratoplasty. AB - The indications for penetrating keratoplasty have changed over the past several years. Nine hundred ninety-nine penetrating keratoplasty specimens from 1981 through 1990 were analyzed. Overall, keratoconus was the most common indication for penetrating keratoplasty (24.2%). This was followed by pseudophakic bullous keratopathy (23.0%), regraft (13.1%), scarring (8.2%), and Fuchs' endothelial dystrophy (5.8%). Pseudophakic bullous keratopathy was the most common indication for penetrating keratoplasty in each year from 1984 through 1989 with a peak in 1987 (33%). Since 1987, the number of pseudophakic bullous keratopathy cases has decreased; and in 1990, keratoconus (33.1%) surpassed pseudophakic bullous keratopathy (24.1%) as the most common indication for penetrating keratoplasty. This decreasing incidence of pseudophakic bullous keratopathy may reflect the discontinued use of closed-looped anterior chamber and iris-plane intraocular lenses most commonly associated with this complication. PMID- 1417538 TI - A randomized, prospective, double-masked clinical trial of Optisol vs DexSol corneal storage media. AB - We compared Optisol and DexSol, two chondroitin-sulfate-based media for corneal storage at 4 degrees C, by transplanting 31 donor cornea pairs (one cornea stored in Optisol and its mate in DexSol for 20 to 134 hours) into 31 pairs of recipients (62 patients). All grafts were clear 1 year after transplantation except for one primary donor failure (Optisol group). Optisol-stored corneas were significantly thinner than DexSol-stored corneas after cardinal suture placement (0.64 mm vs 0.76 mm) and at the end of surgery (0.69 mm vs 0.78 mm); at all points afterward through 1 year the two groups did not differ. The activity of two lysosomal enzymes released into the media during storage, alpha-mannosidase and alpha-glucosidase, was lower in the Optisol group. Epithelial status and all endothelial morphometric parameters, except the figure coefficient at 1 year, did not differ between the two groups before surgery and 3, 6, and 12 months after surgery. Mean endothelial cell loss at 1 year was 15% for the Optisol group and 21% for the DexSol group (P = .22). Thus, Optisol-stored corneas were thinner during surgery than DexSol-stored corneas and there was less lysosomal enzyme activity in the Optisol medium after tissue storage. There were no significant differences in postoperative clinical or endothelial morphometric parameters, however. PMID- 1417540 TI - Computer-assisted corneal topography in parents of patients with keratoconus. AB - Recently developed computer-assisted devices allow detection of early topographic abnormalities of the cornea, including mild or abortive forms of keratoconus. To address the possibility that keratoconus is an inherited condition, we examined both parents of 12 randomly selected patients with keratoconus whom we were following up. Of the 12 sets of parents, at least one parent in each of seven sets had abnormal corneal characteristics. Using previously determined quantitative criteria (eg, central corneal steepening, greater steepening inferiorly than superiorly, and asymmetry between the two eyes) to distinguish normal from keratoconic corneas we found evidence of keratoconus in at least one of the 14 parents. The remaining five patients had parents with normal corneal characteristics. These data support the hypothesis that keratoconus is sometimes an inherited condition, exhibiting, at least in some families, autosomal dominant inheritance with incomplete penetrance. PMID- 1417541 TI - Unexpected cyclotropia simulating disruption of fusion. AB - Fifteen patients with diplopia associated with prior scleral buckling, prior penetrating keratoplasty, severe corneal scarring, monocular aphakia, long standing strabismus, or prior vertical offsets of the horizontal recti were thought to have disruption of fusion because diplopia could not be eliminated with prisms. They were each found to have a substantial symptomatic cyclotropia unassociated with an obvious dysfunction of an oblique muscle. In 13 patients, diplopia resolved after the cyclotropia was corrected surgically. PMID- 1417542 TI - 'V' esotropia and excyclotropia after surgery for bilateral fourth nerve palsy. AB - Six patients had residual diplopia at near in the downgaze position after surgery for bilateral fourth nerve palsy. They all showed a large excyclotropia in the downgaze position that was associated with a "V"-pattern esotropia and could not fuse in the reading position because of the size of the excyclotropia. They were treated with bilateral recessions of the inferior recti, which resulted in an expansion of the single binocular field of vision in downgaze, with an elimination of diplopia in the reading position. None experienced a deterioration in their alignment in the primary position. PMID- 1417543 TI - Radiation therapy of acquired immunodeficiency syndrome-related Kaposi's sarcoma of the eyelids and conjunctiva. AB - We retrospectively studied 42 men with acquired immunodeficiency syndrome-related Kaposi's sarcoma of the conjunctiva or eyelids who were treated with radiation. Forty-nine sites were treated, 35 (71%) of which involved the eyelids, 12 (24%) the conjunctiva, and two (4%) both the eyelids and conjunctiva. Group 1 consisted of 31 sites treated with a single dose of 800 cGy and group 2 consisted of 18 sites treated with a multiple-fraction regimen and total doses between 1500 and 3600 cGy. The response and recurrence rates in the two groups were similar. One patient from group 2 died within 1 month of treatment and was not included in the analysis. The lesions improved in all cases. A complete response was obtained in 10 (32%) of the 31 lesions in group 1, compared with four (22%) of 18 lesions in group 2. A partial response was obtained in 21 (68%) of 31 lesions in group 1, compared with 13 (72%) of 18 lesions in group 2. Expected minor reactions in the treatment field, primarily loss of cilia, were comparable in the two groups. No serious complications were noted. Recurrence occurred in seven (22%) of the 31 sites in group 1 (six patients) and seven (39%) of the 18 sites in group 2 (six patients). The results suggest that a single treatment of 800 cGy is a safe and effective palliative therapy for ophthalmic acquired immunodeficiency syndrome related Kaposi's sarcoma. PMID- 1417544 TI - Ischemic macular edema. Recognition and favorable natural history in branch vein occlusion. AB - Eyes with macular edema caused by retinal branch vein occlusion underwent masked evaluation of fluorescein angiography to determine complete macular perfusion vs incomplete macular perfusion (capillary dropout, ischemia). Cases evaluated as incomplete macular perfusion showed a greater frequency of improvement (91%) in visual acuity than did perfused cases (29%) (P = .003) after a mean follow-up of 39 months. Ischemic edema is often transient, and is associated with a good outcome in visual acuity (median final visual acuity was 20/30). Perfused macular edema has a poorer prognosis for visual acuity (median final visual acuity was 20/80). Macular ischemia is usually associated with a broken foveal capillary ring. Previous animal research on ischemic brain edema has shown that following brain ischemia, an intracellular and an extracellular hypertonic environment lead to intracellular and extracellular edema (cytotoxic edema), which is often followed by vascular protein leakage (vasogenic edema). A similar occurrence in ischemic retina could explain the transient edema reported herein, with good outcome in visual acuity following the spontaneous resolution of edema. PMID- 1417545 TI - Endophthalmitis caused by gram-negative organisms. AB - The medical records of 52 patients (53 eyes) with culture-proven gram-negative endophthalmitis between January 1982 and December 1990 were reviewed. Pseudomonas aeruginosa (23% [12/53]) and Haemophilus influenzae (19% [10/53]) were the most frequent isolates in this series. Overall, 26 (49%) of 53 treated patients achieved 20/400 or better visual acuity. Fifty-two (98%) of the original 53 gram negative isolates were sensitive to the aminoglycoside antibiotics. To determine their sensitivity to recently developed antibiotics, 35 of the isolates were again grown on culture media and their sensitivities to ceftazidime, ciprofloxacin, and imipenem were obtained. Only ceftazidime demonstrated in vitro efficacy for all the organisms tested. PMID- 1417546 TI - Intraocular lymphoma. Immunopathologic analysis of vitreous biopsy specimens. AB - Immunologic analysis of cell surface markers (immunophenotyping) has become a standard procedure in the evaluation of systemic lymphomas. However, attempts to apply these techniques to intraocular lymphoma have not been uniformly successful. We successfully immunophenotyped five consecutive cases of intraocular lymphoma using immunoperoxidase surface marker analysis of cytocentrifuged specimens in two cases and flow cytometry in three. In all five cases, a monoclonal B-cell population was unequivocally present. Contrary to previous reports, we found surface marker analysis of vitreous biopsy specimens to be helpful in the diagnosis and treatment of intraocular lymphoma. Not only did it support the cytologic diagnosis but it allowed comparison of the immunophenotype of vitreous infiltrates with that of previous or subsequent lymphomatous lesions from nonocular sites. PMID- 1417547 TI - Maternal cigarette smoking during pregnancy. A risk factor for childhood strabismus. AB - Strabismus is a common ophthalmologic disorder in children that can result in permanent visual loss. A population-based case-control study was conducted to investigate the association between childhood strabismus and prenatal risk factors including maternal smoking. All incident cases of strabismus diagnosed during a 21-month period, from January 1, 1985, to September 30, 1986, in nine metropolitan area pediatric ophthalmology centers were selected for study (n = 377). Controls were children born on the same day and in the same hospital as the cases (n = 377). Data collection included an interview with the biologic mother and abstraction of obstetric and neonatal birth records. Cigarette smoking was associated with esotropia and but not exotropia for those women who smoked throughout pregnancy (odds ratio, 1.8, 95% confidence interval, 1.1 to 2.8, and odds ratio, 1.4, 95% confidence interval, 0.6 to 3.1, respectively). The relative risk for strabismus was not elevated for women who quit smoking before pregnancy or during pregnancy, nor was there evidence of a dose response. The effect of maternal smoking on risk of esotropia was modified by birth weight and gestational age. The association of maternal smoking throughout pregnancy and esotropia was strongest for children who weighed less than 2500 g (odds ratio, 8.2, 95% confidence interval, 1.1 to 62.7) and 3500 g or more at birth (odds ratio, 5.6, 95% confidence interval, 2.1 to 15.4). Exposure to secondary smoke during pregnancy increased the risk of strabismus only when the mother smoked. PMID- 1417548 TI - Interactions between light and vitreous fluid substitutes. AB - To determine the interactions between light and vitreous fluid substitutes, we studied the absorption and fluorescence properties of the following fluids that are commonly used in vitreoretinal surgery: Ringer's solution, balanced salt citrate-buffered solution, balanced salt bicarbonate-buffered solution, hydroxypropyl methylcellulose ophthalmic solution, hyaluronate sodium, perfluorocarbons, silicone oil, and fluorosilicone oil. The absorption spectra for all the fluids peaked in the UV-C (reference range <280 nm) and UV-B (reference range from 315 to 280 nm) regions of the spectrum, with little or no absorption in the visible region of the spectrum (from 400 to 700 nm). Emission of almost all of the fluids occurred mainly in the 300- to 360-nm region, with fairly low-quantum efficiency. The limited light absorption properties of the fluids calls for caution during transpupillary and intraocular laser photocoagulation to avoid excessive retinal damage, mainly when the laser power is increased during treatment. Transmission of incoherent light (environmental and ophthalmic artificial light) through highly transparent vitreous fluid substitutes may lead in time to dangerous light exposure, particularly in aphakic eyes. The emitted fluorescence in these fluids generates a minimal risk of long term damage. PMID- 1417550 TI - Hansen's disease. PMID- 1417549 TI - Biochemical abnormalities in vitreous of humans with proliferative diabetic retinopathy. AB - Vitreous changes in diabetes can exacerbate proliferative diabetic retinopathy. These changes may be due to the effects of diabetes on vitreous collagen. Vitreous samples from 19 patients with proliferative diabetic retinopathy and 23 patients without diabetes were analyzed for collagen crosslinks, as well as for the early glycation products, glucitolyllysine and glucitolylhydroxylysine. Fluorometry was performed to measure advanced glycation end products. Vitreous collagen derived from diabetic patients was found to have significantly higher levels of the crosslink dihydroxylysinonorleucine (3.15 vs 1.24 mol/mol collagen, P<.01) than that of control subjects. Early glycation products were elevated in diabetic vitreous (1.65 vs 0.54 mol/mol collagen, P<.05). Levels of advanced glycation end products were 20 times higher in diabetic vitreous compared with the vitreous of controls. These diabetes-induced alterations of human vitreous may be of particular importance given the role of vitreous in proliferative diabetic retinopathy and vision loss. PMID- 1417551 TI - Endocanalicular laser-assisted dacryocystorhinostomy. An anatomic study. AB - In human cadaver specimens, a laser fiberoptic was advanced through the canalicular systems to create fistulas between the nasolacrimal sac and nose. A 400- to 600-microns, blunt-tipped quartz fiberoptic was then advanced through the upper and/or lower canaliculus to the medial aspect of the nasolacrimal sac. After 10 to 15 laser pulses (10 W for 0.1 second), a 2.5 x 2.5-mm fistula was created between the lacrimal sac and the nose just anterior and inferior to the middle turbinate. Additional laser pulses can further enlarge the fistula. Endocanalicular laser-assisted dacryocystorhinostomy has potential advantages compared with endonasal laser-assisted dacryocystorhinostomy, including the following: laser energy is directed away from the eye; the technique resembles standard nasolacrimal probing; and nasal endoscopy and instrumentation may prove unnecessary. PMID- 1417552 TI - Ophthalmology in Laos. AB - Laos, a small, landlocked nation of 4 million persons, has only recently begun modernization of its medical services, now a national priority. Five ophthalmologists and 11 cataract surgeons are responsible for the entire country. Tertiary care is available only at two centers; the first eye hospital opened in 1990. Several voluntary organizations have recently become involved in assisting with the development of services. PMID- 1417553 TI - Medication review. PMID- 1417554 TI - Facial trauma. Assessment and treatment. AB - Management of facial trauma requires immediate attention to patency of the airway and to circulation. This article outlines an assessment procedure for patients with facial injuries and presents treatment guidelines. PMID- 1417555 TI - The normal development of teeth. AB - Even though a dental assessment is not often a part of a child's regular medical check up, an understanding of the normal dental development and its variations is a valuable diagnostic tool. Dental health is a part of total health, and there is a need for increased communication between medical and dental practitioners to achieve this goal (Figure 32). PMID- 1417556 TI - A management approach for temporomandibular disorders. AB - Conservative, non invasive and reversible treatment is possible and highly successful for most temporomandibular disorder patients. Unfortunately, at this time it is not possible to provide preventive therapy or predict an 'at risk' group. Perpetuating and aggravating factors can sometimes be identified and eliminated in patients suffering from a TMD. TMD treatment can also be of benefit for chronic headache patients. A logical approach to the management of TMJ disorders has been outlined that emphasises the principle of 'escalation of therapy'. This has the advantage of avoiding overtreatment and maintaining patient confidence if initial attempts fail. PMID- 1417557 TI - Oral ulceration. AB - Oral ulceration is a common problem. The presentation is often very similar, irrespective of the underlying cause. This paper illustrates some of the more commonly encountered forms of oral ulceration. PMID- 1417558 TI - Lifestyle change and cardiovascular disease. Principles and practice. AB - Changes in patients' lifestyles can be approached in a practical fashion by working through the relevant 'stages of change'. Helping patients to change their lifestyles does not have to be a very time-consuming process for the clinician, but it does require planning, and attention to those factors that are important at each stage of the process. Although this paper has a focus on lifestyle change for the reduction of CVD risk factors, the same principles can apply to lifestyle change and disease prevention for other disorders. PMID- 1417559 TI - Aerosol devices in the treatment of asthma. Technical and clinical factors. AB - Inhaled medications are capable of producing the best bronchial effect with fewest systemic side effects. Proper inhalation technique is critical if these devices are to be effective. Specific aspects of both the system and the inhaler technique used are critical in achieving optimal performance. Observation of each patient's inhaler technique is advised--it is not enough to merely give instructions or to simply discuss the therapy. Both efficacy and side effects are dose dependent; high doses of topical bronchodilators and anti-inflammatory drugs are appropriate for some patients. Protection against side effects may be achieved by gargling mouth and throat after use, or by using a spacing (holding) chamber. Long-term compliance with medication will be best if the number of doses used, and the side effects, are minimised. PMID- 1417560 TI - Temporomandibular joint dysfunction. Guidelines for patients. PMID- 1417561 TI - P wave abnormalities. PMID- 1417562 TI - Certification of asthma death by general practitioners. AB - Although asthma may be a prominent feature in many cases of terminal illness, it is often incorrectly named as the cause of death. It is difficult to assess asthma death in the older age groups where psychosocial factors are prominent. This review looks at the certification by general practitioners of 50 consecutive cases of asthma death. PMID- 1417563 TI - Pain in the face. AB - The outstanding cause of pain in the face is dental disease, but various neuralgias and infections such as maxillary sinusitis require consideration. A careful history and examination is the basis of diagnosis. PMID- 1417564 TI - Learning about research. PMID- 1417565 TI - Hormone replacement therapy. PMID- 1417566 TI - Never-ending stories. PMID- 1417567 TI - Practice grants: alms for the poor. PMID- 1417568 TI - Patient education. Establishing breastfeeding. PMID- 1417569 TI - A case of human bite. PMID- 1417571 TI - Bicycle helmet survey. PMID- 1417570 TI - Pathologists put their point of view. PMID- 1417572 TI - Euthanasia opposed. PMID- 1417573 TI - The hearing of the patients treated with hemodialysis: a long term follow-up study. AB - Sensorineural hearing loss is frequently found in the patients under the treatment with hemodialysis, but the responsible etiological factor(s) still remains controversial. The purpose of the present study was to determine by a long term follow-up study whether hemodialysis per se or other factors induce sensorineural hearing loss. Thirty-seven patients with the observation periods of 4 years or longer were selected for the analysis. Hearing tests were performed soon after the initiation of hemodialysis and every 3 to 12 months thereafter. Significant hearing loss was found in 16 cases (31 ears) at the first test. Although 3 cases (5 ears) of the initially normal group and one case (2 ears) of the group with already existing hearing loss exhibited significant hearing loss, the change in the hearing level was quite minimal in remaining 67 ears during the observation period. Although the cochlea in patients under the treatment with hemodialysis is susceptible to various insults, we conclude that hemodialysis per se does no harm to the cochlea and the hearing can be maintained at the pre hemodialysis level in the majority of the cases. PMID- 1417574 TI - Basic study on the effect of nasally administered salmon calcitonin preparation on the nasal ciliary epithelium. AB - Nasal administration of drugs is an administration method which is worthy of attention. In such therapy, local administration should not damage the nasal mucous membranes. In the present study, we conducted an investigation by the tissue culture test method of the functional and morphological effects of new nasal calcitonin preparation, which is being developed as a nasal spray agent for osteoporosis, on the nasal ciliary epithelium. The nasal septal mucous membranes of C3H-strain mice were used, and 5 types of nasal calcitonin preparations with a microcrystalline cellulose base and additives added were used. The various drugs were added to nasal mucous membrane slices in RPMI-1640 culture medium; ciliary activity before addition and 0.5, 2, and 4 hr after was electrophotometrically measured; and morphological observation was then carried out by SEM. In the various additive groups, virtually no effect on ciliary activity was observed, and the same results were obtained when 3 and 9 times the estimated clinical spray dosage was added. Moreover, in morphological observation by SEM, in the various additive groups, no morphological changes in samples of nasal ciliary specimens were observed after 4 hr of culturing at the maximum administered dosage (9 times the estimated clinical spray dosage). Based on these findings, it was concluded that the series of calcitonin preparations with various additives had no hazardous effect on the nasal ciliary epithelium. PMID- 1417575 TI - NaOH cell maceration/scanning electron microscopic studies on the architecture of the lamina propria of the mouse palate. AB - NaOH cell-maceration/SEM method was applied to the oral surface of the mouse palate to demonstrate the three-dimensional architecture of the lamina propria. In the caudal part of the hard palate, the lamina propria was characterized by the conspicuous parallel ridges which ran side by side in sagittal direction. In the boundary between the hard palate and the soft palate the parallel ridges interrupted abruptly, in the soft palate the ridges were extremely undeveloped to show the shrunken cloth-like appearance. Furthermore, the conical connective tissue papillae were lined up along the boundary. These findings suggest that the boundary between the hard plate and the soft palate is clear not only in the bony structure but in the lamina propria, and that the parallel ridges in the hard palate play an important role in ensuring from the excessive extending force during mastication. PMID- 1417576 TI - Adherence of Haemophilus influenzae to middle ear mucosa injured by killed H. influenzae. AB - Repetitive acute otitis media is due to recurrent bacterial infection of middle ear superimposed on chronic otitis media with effusion. Endotoxin, one of the constituents of Haemophilus influenzae, is present in some cases in the middle ear effusion of otitis media with effusion and has been demonstrated experimentally to damage the middle ear mucosa. The aim of this study was to determine the effect of killed H. influenzae on the adherence of H. influenzae and H. parainfluenzae to the middle ear epithelial cells. The numbers of adherent organisms per epithelial cell in ears inoculated previously with killed H. influenzae or with normal saline (0.9% NaCl) were compared. Prior middle ear inoculation of killed H. influenzae enhanced the adherence of H. influenzae to middle ear epithelial cells, but it had little effect on the adherence of H. parainfluenzae. H. influenzae adhered to middle ear epithelial cells in greater numbers than H. parainfluenzae. Results demonstrate that a middle ear pathogen adheres to middle ear epithelial cells presumably damaged by killed H. influenzae, whereas a non-pathogen does not. These findings might partly explain the increased susceptibility of an ear with chronic otitis media with effusion to recurrent infection with H. influenzae. PMID- 1417577 TI - Incidence of attic retraction after staged intact canal wall tympanoplasty for middle ear cholesteatoma. AB - Incidence of retraction pocket and recurrent cholesteatoma in the attic after surgery for middle ear cholesteatoma using the staged intact canal wall technique were investigated in 95 ears of 91 patients, all of which had various degrees of bone defect in the tympanic scutum. Surgical procedures employed in the second stage for prevention of attic retraction were classified into three types: Type I, no scutumplasty; Type II, scutumplasty; Type III, scutumplasty plus mastoid obliteration. In 83 ears followed up for more than 1 year after the second stage, such retraction troubles occurred in 2 of 13 ears (15%) in Type I, 8 of 20 ears (40%) in Type II, and 24 of 50 ears (48%) in Type III. Incidence of retraction troubles was higher in Types II and III, probably because these procedures were indicated in ears with large scutum defects. Dislocation and atrophy of the graft materials, together with bone resorption around the bone defect were the main reasons for failure in scutumplasty. Dysfunction of the eustachian tube and traction of the eardrum by the scar tissue behind it may have also contributed to attic retraction. Mastoid obliteration with small blocks of hydroxyapatite was more effective in prevention of retraction troubles than that with pedicled temporalis muscle flap. PMID- 1417578 TI - A visual suppression test using post-rotatory nystagmus. AB - The visual suppression test is one method for examining the function of visual fixation and visual influence on vestibular nystagmus. In this study the visual suppression test using post-rotatory nystagmus was investigated in 65 normal subjects and 142 clinical cases with cerebellar lesions. In 65 normal subjects the mean +/- standard deviation of visual suppression of the slow phase velocity on post-rotatory nystagmus was 69 +/- 11%. As to the stimulation for visual suppression test, the post-rotatory method using rotatory stimulation is milder than caloric stimulation. This method is far simpler to analyze than the visual suppression test using pendular rotatory nystagmus and other vestibulo-ocular reflex tests. In the 142 patients with cerebellar lesions, reduced or abolished visual suppression on post-rotatory nystagmus was seen in 89 patients with radiologically confirmed disturbances in the vestibulo-cerebellum. And this method could identify the lesion side in the cerebellum. These results showed a correlation between the visual suppression test using post-rotatory nystagmus and one using caloric nystagmus in 65 normal subjects and 142 clinical cases with cerebellar lesions. PMID- 1417579 TI - Endolymphatic hydrops induced by noise exposure. AB - In animal with cochlear deafness induced by firecracker explosion, fibrous degeneration of the endolymphatic sac was observed 4 months after the disappearance of Preyer's reflex. Endolymphatic hydrops induced by noise exposure may develop as the results of degeneration of the endolymphatic sac due to cochlear deafness by acoustic trauma after the lapse of a long period of time. PMID- 1417580 TI - Effects of increasing photoperiod length and anticoccidials on performance and health of roaster chickens. AB - Male broiler chickens were raised to 63 days of age under different lighting and anticoccidial treatments. A constant-light program was compared with two interrupted and increasing-light programs in which the photoperiod length was 6 hours between 7 and 14 days of age and then increased gradually to continual light by 49 days of age in the first program and more gradually to 18 hours by 49 days of age in the second program. By 63 days of age, the increasing-light programs significantly increased body-weight gain and decreased feed/grain ratio, but not significantly. The increasing-light programs reduced the incidence of skeletal disease from 7.56% to 2.88% in the first program and to 3.53% in the second program, reduced the incidence of acute death syndrome from 5.94% to 3.37% in the first program and to 4.65% in the second program, and reduced total mortality from 18.81% to 11.71% in the first program and to 11.38% in the second program. The lighting programs had no effect on the incidence of ascites and right heart failure, the ratio of right ventricular weight to total ventricular weight, the incidence of clinical and subclinical tibial dyschondroplasia, and the number of cartilaginous and osseous nodules in the lungs. The anticoccidials compared were monensin and amprolium/ethopabate, from 0 to 35 days of age. These treatments had no significant direct effects on any of the parameters measured. PMID- 1417582 TI - Virulence factors of Escherichia coli associated with colisepticemia in chickens and turkeys. AB - Four hundred twenty turkey and 80 chicken Escherichia coli isolates from colisepticemic birds were examined for the following properties: heat-labile toxin (LT), heat-stable enterotoxin, verotoxin, colicinogenicity, hemolysin, and hydroxamate/aerobactin production. Twenty-four (5.7%) of the 420 turkey isolates and six (7.5%) of the 80 chicken isolates produced an LT that was cytotoxic for both Vero and Y-1 cells. In contrast, 48 (11.4%) of the turkey isolates and 18 (22.5%) of the chicken isolates produced a distinct LT that was cytotoxic only for Vero cells. In addition, 64 (80.0%) of the chicken isolates and 309 (74.0%) of the turkey isolates produced aerobactin. Colicinogenicity occurred in 51 (64.0%) of the chicken isolates, with 41 (51.0%) producing colicin V. By contrast, 254 (61.0%) of the turkey isolates produced a colicin, of which 176 (42.0%) produced colicin V. None of the chicken and turkey isolates produced hemolysin or heat-stable enterotoxin. PMID- 1417581 TI - The influence of diet on necrotic enteritis in broiler chickens. AB - Necrotic enteritis was reproduced in broiler chickens by mixing cultures of Clostridium perfringens in the feed. Mortality due to necrotic enteritis was higher among chickens fed rations based on wheat, rye, barley, and oat groats than among chickens fed corn-based rations. Addition of pentosanase to a wheat based diet did not affect the level of mortality due to necrotic enteritis. Addition of pectin and guar gum to different rations severely reduced growth rate and eliminated necrotic enteritis from test birds. Addition of glucose to a corn based diet caused a small increase in mortality due to necrotic enteritis. PMID- 1417584 TI - Use of a pilocarpine-based lavage procedure to study secretory immunoglobulin concentration in the alimentary tract of White Leghorn chickens. AB - A lavage procedure was used to study the kinetics of alimentary fluid IgA concentration in 15 specific-pathogen-free white leghorn chickens for 8 weeks post-hatch. Lavage solution was administered orally and collected from the distal alimentary tract following an intraperitoneal injection of pilocarpine. Concentrations of IgA, quantitated by enzyme-linked immunosorbent assay, were more than 0.04 mg/ml by 3 weeks and were negligible before this age. This level gradually increased over the next 5 weeks, peaking at nearly 0.4 mg/ml at 8 weeks of age. Alimentary lavage was easy to perform, required no necropsy or surgical manipulation, and facilitated repeated collection of alimentary fluid from live birds. Repeated lavage did not alter concentrations of IgA and IgG in alimentary fluid, and concentrations of IgA and IgG in alimentary fluid were stable during incubation at 37 C for 24-48 hr. PMID- 1417583 TI - Relationship of the enzyme-linked immunosorbent assay to indirect immunofluorescent antibody test for the detection of so-called chicken anemia agent antibodies in serum from broiler breeders. AB - Serum samples collected from breeder chickens ranging in age from 1 day to 55 weeks were tested for CAA antibodies by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescent antibody (IFA) test. The relationship of ELISA to IFA test was determined. The sensitivity of the ELISA relative to the IFA test was 82.64%, and the specificity of the ELISA relative to the IFA test was 56.25%. Agreement between the ELISA and the IFA test was highly significant (Kappa = 0.74, Z = 5.78). We concluded that the ELISA is as good as the IFA test for detecting CAA antibody in sera from chickens. PMID- 1417585 TI - Pathogenicity differences of multiple isolates of Aspergillus fumigatus in turkeys. AB - Sixteen Aspergillus fumigatus isolates of environmental, mammalian, and avian origin were used to assess: 1) intra-air-sac inoculation as a viable challenge alternative to aerosol exposure, and 2) isolate variability in pathogenicity. Development of lesions, antibody response in survivors, mortality, and weight gains were assessed. Turkey poults were challenged with equal numbers of viable conidia. Total number of conidia given per experimental group varied markedly and did not influence mortality. Antibody response as measured by the enzyme-linked immunosorbent assay and agar gel immunodiffusion test was erratic, although most poults with high antibody scores had marked lesions and low weight. Lesions were characterized by necrogranulomatous pneumonia and airsacculitis with marked visceral involvement. The source of the isolate was not a factor in mortality, although this was biased by the high numbers of isolates from birds with aspergillosis. The single environmental isolate produced no mortality. PMID- 1417587 TI - Genetic variation in resistance of turkeys to experimental infection with Newcastle disease virus. AB - Seven hundred eighty male and female turkeys representing four genetic lines were challenged in four experiments with the Texas GB strain of Newcastle disease virus (NDV). The lines of turkeys included two randombred control lines (RBC1 and RBC2), a subline (E) of RBC1 selected for increased egg production, and a subline (F) of RBC2 selected for increased 16-week body weight. Mortality in turkeys of subline F (32.5%) was significantly higher than that in turkeys of line RBC2 (15.8%), subline E (17.5%), and line RBC1 (18.4%). At the end of each experiment, surviving birds were tested for antibody to NDV using the enzyme-linked immunosorbent assay (ELISA) and hemagglutination-inhibition (HI) test. Turkeys of subline E and line RBC1 had significantly lower ELISA antibody titers than those of subline F and line RBC2. Subline F had the highest HI antibody titers, followed in decreasing order by lines RBC2 and RBC1 and subline E. No apparent correlation was found between antibody response and mortality after NDV challenge. PMID- 1417586 TI - Production and characterization of monoclonal antibodies to budgerigar fledgling disease virus major capsid protein VP. AB - Eleven hybridoma cell lines producing monoclonal antibodies (MAbs) against intact budgerigar fledgling disease (BFD) virions were produced and characterized. These antibodies were selected for their ability to react with BFD virions in an enzyme linked immunosorbent assay. Each of these antibodies was reactive in the immunofluorescent detection of BFD virus-infected cells. These antibodies immunoprecipitated intact virions and specifically recognized the major capsid protein, VP1, of the dissociated virion. The MAbs were found to preferentially recognize native BFD virus capsid protein when compared with denatured virus protein. These MAbs were capable of detecting BFD virus protein in chicken embryonated cell-culture lysates by dot-blot analysis. PMID- 1417588 TI - Economic effects of clinical chicken anemia agent infection on profitable broiler production. AB - An outbreak of anemia dermatitis syndrome caused by chicken anemia agent (CAA) occurred in 15 broiler flocks. An average of 29% of chickens in these flocks were derived from a common breeder flock. The breeder flock had no antibody to CAA at 20 weeks of age but had seroconverted by 31 weeks. Diseased broiler flocks were derived from eggs laid by the breeder flock between 25 and 30 weeks of age. CAA infection in the breeder flock was subclinical, with no apparent effects on mortality or performance. A strategic program of therapeutic and/or prophylactic antibiotic therapy was begun in affected broiler flocks as soon as the disease was diagnosed. Nevertheless, when the cost of therapy was taken into account, affected broiler flocks had a net income 17.3% to 19.6% lower than normal flocks. Average bird weights were 3.3% to 3.5% lower in affected flocks than in unaffected flocks, and affected flocks had a significantly greater proportion of lighter birds. Average mortality in affected flocks was 2.0% to 2.3% higher than in normal flocks, with peak mortality occurring in the third week of life. There was no apparent effect on feed-conversion ratio. PMID- 1417589 TI - Cardiac muscle mass distribution in the domestic turkey and relationship to electrocardiogram. AB - Ventricular weights were measured in 20-week-old male and female heavy turkeys, and electrocardiograms (ECGs) were recorded in 10- and 20-week-old male and female heavy turkeys. Twenty-week-old males had heavier relative left ventricular and total ventricular weights than females of the same age. Left-to-right ventricular weight ratios were 4.4:1 in males and 4.5:1 in females. Heart rate was faster in young birds and in females, and that influenced the duration of the intervals of the ECG. Wave amplitudes were smaller in 10-week-old turkeys than in 20-week-old turkeys. There was no correlation between electrocardiographic parameters and ventricular weights of male and female turkeys. Two-dimensional ECGs were therefore found to be of minimal value for detecting turkeys with heavier ventricles. PMID- 1417590 TI - Effects of corticosteroids on lymphocyte subpopulations and lymphokine secretion in chickens. AB - Various effects of glucocorticosteroids on the avian immune system were examined in chickens treated intramuscularly with 0.1 to 2.5 mg dexamethasone or prednisolone. Kinetic changes in body weight gain, percentages of lymphocyte subpopulations, and T-cell functions were examined following treatment with dexamethasone or prednisolone every other day. Chickens treated with dexamethasone or prednisolone showed a decrease in body-weight gain compared with age-matched, untreated chickens. In general, the total number of splenic lymphocytes of chickens treated with the two drugs was significantly lower than in controls in a dose-dependent manner. Flow cytometric analysis of splenic lymphocyte subpopulations revealed that the percentages of lymphocytes expressing CD8, gamma delta T-cell receptor, Ia, or IgM antigens and natural killer cells were lower in dexamethasone-treated chickens than in the controls, whereas the percentages of T lymphocytes bearing CD3, CD4, or alpha beta TCR antigens were higher. Furthermore, splenic T cells obtained from dexamethasone-treated chickens showed a significant depression in concanavalin A-induced lymphoproliferation and interleukin 2 and gamma-interferon production. The results characterize a variety of immunosuppressive effects of glucocorticoids on the avian immune system. PMID- 1417591 TI - Microbiological and histopathological effects of an induced-molt fasting procedure on a Salmonella enteritidis infection in chickens. AB - A study was undertaken to determine if a 2-week feed-removal protocol, as is used by industry to induce a molt in aging hens, would affect the course of a Salmonella enteritidis infection. White leghorn hens aged 69-84 weeks were deprived of feed to induce a molt, and on day 4 of the fast, the birds were orally infected with 5 x 10(6) S. enteritidis. S. enteritidis organisms were enumerated in the spleen on day 6 and from the alimentary tract on days 7, 14, 21, 28, and 35. Little difference was detected in numbers of S. enteritidis from spleens of molted and unmolted hens. Significantly more molted hens shed detectable intestinal S. enteritidis than unmolted hens on day 14 (one of two trials) and day 21 (one of two trials). Intestinal levels of S. enteritidis were increased 100- to 1000-fold in the molted birds on day 7 (one of two trials) and day 14 (two of two trials), and many of the hens exhibited bloody alimentary secretions. Histological examination of the intestinal tract of S. enteritidis infected molted hens showed increased inflammation in the epithelium and lamina propria of colons and ceca, compared with unmolted infected hens. PMID- 1417592 TI - The role of mice in the epizootiology of Salmonella enteritidis infection on chicken layer farms. AB - A microbiological survey of 10 mice-infested poultry farms was conducted to determine the role of mice in the epizootiology of S. enteritidis infection. Five of the farms were rated as clean of S. enteritidis and five as contaminated based on culture results of environmental samples for S. enteritidis. Of 2103 environmental samples and 715 mice and rats tested, 5.1% and 16.2%, respectively, were culture-positive for S. enteritidis. On contaminated farms, S. enteritidis was isolated from 24.0% of the mice and 7.5% of the environmental samples, which represented 75.3% of all Salmonella isolations from mice but only 18.0% of Salmonella isolations from environmental samples on these farms. S. enteritidis was not detected in mice on clean farms. Phage types 13a and 14b were the two most frequently isolated phage types from mice and environmental samples. Although only a single phage type was isolated from single free-standing poultry houses, multiple phage types were isolated from multi-house complexes. A bacterial count from the feces of one mouse yielded 2.3 x 10(5) S. enteritidis bacteria per fecal pellet. S. enteritidis persisted at least for 10 months in an infected mouse population. PMID- 1417593 TI - An evaluation of inactivated infectious coryza vaccines containing a double emulsion adjuvant system. AB - The efficacy of experimental inactivated infectious coryza vaccines produced by a commercial vaccine manufacturer was evaluated. The vaccines, containing as the adjuvant phase either a double-emulsion mineral oil system or aluminum-hydroxide gel, were administered to 6-week-old chickens as a single dose. Some vaccines were a monovalent product containing a Page serovar C Haemophilus paragallinarum strain, and others were a bivalent product containing both Page serovar A and serovar C strains. After 3 weeks, all chickens were challenged by infraorbital sinus inoculation of virulent H. paragallinarum, either Page serovar C (strain HP31) or Page serovar A (strain HP14). The monovalent serovar C double-emulsion based vaccines gave significant protection against a serovar C challenge, with the level of protection varying from 60% to 100%. The monovalent serovar C aluminum-hydroxide-gel vaccine also gave significant protection (94%) against a serovar C challenge. The bivalent double-emulsion vaccine gave significant protection against challenge from both serovars (100% for serovar C and 83% for serovar A). Although no major adverse reactions were detected, some chickens receiving both the double-emulsion vaccines and the aluminum-hydroxide vaccine developed relatively minor granulomatous reactions at the site of injection. PMID- 1417594 TI - Occurrence of Salmonella enteritidis in the U.S. commercial egg industry: report on a national spent hen survey. AB - In order to estimate the prevalence and distribution of Salmonella enteritidis in U.S. commercial egg-production flocks, a survey of spent laying hens was conducted over a 3-month period. Seven of the 10 largest spent-hen processing plants in the United States participated. Ceca were sampled twice weekly from birds presented for slaughter at these plants. Samples were cultured for Salmonella and S. enteritidis, and S. enteritidis isolates were phage-typed. Overall, 23,431 pooled cecal samples were collected from a total of 406 layer houses. Salmonella (any serotype) and S. enteritidis were recovered from 24% and 3% of the pooled samples, respectively. The distribution of S. enteritidis phage types was consistent with data reported by others. Regionally, the estimated prevalence of S. enteritidis-positive houses (i.e., at least one positive sample found in a house) for the Northern, Southeastern, and Central/Western regions was 45%, 3%, and 17%, respectively. Overall, the prevalence of Salmonella-positive houses was 86%. PMID- 1417595 TI - Correlation between the ability of Haemophilus paragallinarum to acquire ovotransferrin-bound iron and the expression of ovotransferrin-specific receptors. AB - To investigate the mechanisms of iron acquisition in avian haemophili, strains of Haemophilus paragallinarum and H. avium were tested for siderophore production and utilization of transferrin iron for growth. No evidence of siderophore production was detected in either of these species using a functional screening assay. H. paragallinarum, but not strains of H. avium, was able to acquire iron from 30% saturated chicken and turkey transferrins but not from human, porcine, or bovine transferrins. In response to iron limitation, H. paragallinarum expressed four iron-regulated outer-membrane proteins of 53, 62, 66, and 94 kilodaltons (kDa). Only the 53- and 94-kDa proteins were detected in the H. avium strains. Using affinity methods, the 94- and 53-kDa proteins were isolated specifically by chicken or turkey transferrin, indicating that they may be equivalent to transferrin binding proteins (TBP1 and TBP2, respectively) isolated from other bacterial species. The isolation of the 62- and 66-kDa proteins in association with TBP1 and TBP2 under less stringent washing conditions only in H. paragallinarum implicates these proteins in the iron acquisition process. PMID- 1417596 TI - Correlation of water activity and other environmental conditions with repeated detection of Salmonella contamination on poultry farms. AB - Three flocks on 13 different broiler farms were monitored for Salmonella over three consecutive growout periods using the drag swab (DS) technique. One house was consistently negative for Salmonella contamination (7.7%); four houses were consistently positive (30.8%); and eight houses (61.5%) alternated between either a DS Salmonella-negative or -positive status. Simultaneously, numerous environmental parameters of the litter surface were measured, including water activity (Aw), ammonia, temperature, pH, moisture content (MC), ash content, and volatile solids. Analysis of these data as a corollary to either Salmonella negative or -positive DS results revealed significant correlation coefficients for some of the parameters, especially Aw. The results suggest that there should be further exploration of remedial intervention based on control of some of the physical features of litter (e.g., controlling litter Aw and possibly MC and pH levels) in poultry houses. PMID- 1417597 TI - Relationship of complement resistance and selected virulence factors in pathogenic avian Escherichia coli. AB - Complement resistance, antibiotic resistance profiles, and virulence profiles of 80 Escherichia coli isolates from the intestines of normal chickens (40 isolates) and chickens diagnosed as having colisepticemia (40 isolates) were compared. Differences were observed between the two groups for antibiotic resistance, siderophore production, presence of type 1 pili, complement resistance, motility, and size of plasmids. The systemic isolates were more likely to have siderophores and type 1 pili, and to be complement-resistant and motile than were the intestinal isolates. No differences between the two groups were observed for colicin production. Further comparison of the 10 most complement-resistant isolates from the systemic group and 10 most complement-sensitive isolates from the intestinal group revealed a correlation between an isolate's resistance to complement and its ability to kill embryos, express type 1 pili, and be motile. Virulence of avian E. coli strains appears to be correlated with complement resistance and the interaction of this resistance with the ability to produce type 1 pili and be motile. PMID- 1417598 TI - Incidence of anemia and polycythemia in clinically ill Georgia broilers. AB - The incidence of anemia and polycythemia was established in clinically ill Georgia broilers that were tested for packed cell volume (PCV) during 1988 and 1989. More than 66% (324/488 = 66.4%) of PCV-tested broiler chicks were anemic, and less than 2% (8/488 = 1.6%) of PCV-tested chicks were polycythemic. The incidence of anemia was significantly (P less than 0.001) higher than expected (2.5%) at age 7 days (56.9%), 14 days (83.9%), 21 days (74.7%), 28 days (58.7%), and 35 days (57.9%). The incidence of polycythemia was significantly (P less than 0.001) higher than expected (2.5%) in 35-day-old broilers (21.1%) but was not significantly different from the expected rate in broilers at age 7 days (0%), 14 days (1.8%), 21 days (0.3%), and 28 days (4.3%). The established rates for anemia were much higher than we would have hypothesized. This led us to believe that either 1) an etiology for anemia is present in epizootic proportions in Georgia broilers, or 2) the standard method for establishing reference intervals for anemia in animals does not apply to broiler chicks. PMID- 1417599 TI - Effects of ascorbic acid on stress and disease in chickens. AB - White leghorn chickens were given feed containing 100 mg of ascorbic acid (AA)/kg. One day later, treated chickens and a similar group of unmedicated control chickens were chilled for 1 hour at 6 C, exposed to an unusual sound, fasted, or subjected to rough handling. Heterophil:lymphocyte (H:L) ratios were determined one day later. The AA-treated birds had significantly lower H:L ratios than untreated controls. Chickens that received a diet containing AA had lower H:L ratios than controls (0.86 vs. 1.65) following administration of adrenocorticotropic hormone. Chickens fed a diet containing AA showed increased resistance to a combined Newcastle disease virus-Mycoplasma gallisepticum infection and to a secondary Escherichia coli infection, as well as to a primary E. coli challenge infection. The effects of AA and an antibacterial drug (furaltadone) were additive. In all experiments, the optimum dose of AA was 100 mg/kg of feed. There was a negative correlation between AA level in the diet and feed efficiency. PMID- 1417600 TI - An atypical strain of Pasteurella gallinarum: pathogenic, phenotypic, and genotypic characteristics. AB - The pathogenicity of a strain of Pasteurella gallinarum isolated in Fresno County, Calif., was compared with the American Type Culture Collection (ATCC) strain. Broiler chickens were inoculated intranasally with 10(7) colony-forming units (CFU) and intramuscularly with 10(5) CFU of each strain. The only notable lesions were in chickens inoculated intramuscularly with 10(5) CFU of the Fresno strain, which developed severe myositis at the inoculation site, pericarditis, perihepatitis, airsacculitis, and synovitis. P. gallinarum was reisolated from these lesions. Phenotypic characteristics of the two strains were identical except in reactions in ONPG broth and fermentation of xylose. Protein-banding patterns for the two strains were identical except for a single band difference in the 35-kilodalton region. Restriction endonuclease analysis confirmed that the Fresno strain was a distinct one. Plasmid analysis revealed that the ATCC strain had two plasmids and the Fresno strain had none. PMID- 1417601 TI - Adaptation of the Sensititre broth microdilution technique to antimicrobial susceptibility testing of Mycoplasma gallisepticum. AB - A technique is described for determining the antimicrobial susceptibility of Mycoplasma gallisepticum, using the Sensititre broth microdilution system. Fourteen M. gallisepticum field isolates and one reference isolate (R-strain) were tested in duplicate against seven antimicrobials. Isolates were susceptible to oxytetracycline, furaltadone, and lincomycin/spectinomycin, but not to amoxycillin and apramycin. Susceptibility to erythromycin and tylosin varied. These data are in agreement with those reported by other workers using more traditional methods, but this adaptation of the broth microdilution technique eliminates any variation attributable to the time-consuming preparation of antimicrobial dilutions associated with these methods. PMID- 1417602 TI - Effects of Eimeria mitis on egg production of single-comb White Leghorn hens. AB - Single-comb white leghorn hens infected with either B4 or C2 strain of Eimeria mitis produced watery droppings as early as day 5 PI. E. mitis infection did not affect egg weight. However, specific gravities of the eggs produced by the hens infected with E. mitis were lower than those produced by the controls. Egg production was significantly reduced temporarily, but most birds returned to production within 14 days. Many of the birds that ceased to lay went through a complete-body molt (56% of the C2-infected hens and 20% of the B4-infected hens). Hens that ceased to lay regained considerable amounts of pigment in their skin, beaks, and shanks. PMID- 1417603 TI - Dose-titration to confirm the level of fenbendazole for control of Raillietina cesticillus in broiler chickens. AB - A total of 452 broiler chickens, naturally infected with Raillietina cesticillus, were allotted into six treatment groups. One group was fed unmedicated broiler ration (Group 1), and the other five groups were fed broiler ration containing fenbendazole at 180 ppm for 3 days (38.5 mg/kg body weight [BW]), 240 ppm for 3 days (50.9 mg/kg BW), 120 ppm for 6 days (52.2 mg/kg BW), 180 ppm for 6 days (79.9 mg/kg BW), or 240 ppm for 6 days (104.3 mg/kg BW). Fenbendazole was 100.0% efficacious against R. cesticillus when administered in the diet at 240 ppm for 6 days; 99.9% at 240 ppm for 3 days and at 180 ppm for 6 days; 99.5% at 120 ppm for 6 days; and 96.9% at 180 ppm for 3 days. Fenbendazole treatment had no adverse effect on weight gain or feed intake. PMID- 1417604 TI - Development and comparison of serologic methods for diagnosing chicken anemia virus infection. AB - This paper describes the development of an indirect immunoperoxidase assay (IIP) and an indirect enzyme-linked immunosorbent assay (ELISA) for detecting antibodies to chicken anemia virus (VAC). The IIP assay developed used CAV infected MDCC-MSB1 cells for detecting antibody to CAV, whereas the ELISA utilized gradient-purified immunoadsorbed CAV as the target antigen. The IIP and ELISA were compared with the standard indirect immunofluorescent antibody (IFA) assay, which is more conventionally used to screen chicken serum for antibodies against CAV. Comparative test results of 185 field samples of chicken serum by these three methods were in agreement 84% of the time. Both IFA and IIP assays yielded fewer positive tests than did the ELISA. IFA and IIP assays were in agreement 93% of the time, as compared with 91% agreement of IIP and ELISA results, or 84% agreement for comparative IFA and ELISA results. PMID- 1417605 TI - Blood oxygen concentration of fast-growing and slow-growing broiler chickens, and chickens with ascites from right ventricular failure. AB - Percent hemoglobin oxygen saturation was measured with a pulse oximeter in 6-week old slow-growing (light) and fast-growing (heavy) male broiler chickens and those with ascites from right ventricular failure (RVF). Pulse rate and percent oxygen saturation were read from the ulnar artery just proximal to the carpus. Percent oxygen saturation was significantly (P less than or equal to 0.0001) higher in light chickens (mean 91.6%) than in heavy chickens (mean 86.0%), and the percent oxygen saturation was significantly (P less than or equal to 0.0001) higher in both groups with normal hearts than in the group with RVF from valvular insufficiency (mean 62.1%). All RVF chickens and those with normal hearts were confirmed at necropsy. Light chickens were males with leg deformity or stunting and were 20-50% lighter than the heavy chickens. PMID- 1417606 TI - Pen oxygen concentration and pulmonary hypertension-induced right ventricular failure and ascites in meat-type chickens at low altitude. AB - Percentage O2 and CO2 were measured in the air in environmentally controlled commercial poultry pens (altitude approximately 300 m) containing broiler or roaster chickens 14 to 56 days of age. Outside air (mean of 10 samples) measured 20.85% O2 and 0.041% CO2. Air in the pens had significantly lower O2 and higher CO2 than outside air; however, air in 25 pens with a high incidence of ascites (mean 20.50% O2, 0.264% CO2) was not different from the air in 25 pens with a low incidence of ascites (mean 20.49% O2, 0.319% CO2). The lowest pen O2 was 20.20%, which would not cause reduced hemoglobin saturation (percent oxygen) of the arterial blood of normal chickens. PMID- 1417607 TI - Suspected sodium toxicity in hand-reared great blue heron (Ardea herodias) chicks. AB - Sodium toxicity was suspected in hand-reared great blue heron (Ardea herodias) chicks fed herring frozen in brine (seawater). Affected chicks were lethargic with stiff legs that extended to the posterior, and breathing was labored. Chicks regurgitated food or refused to eat. All chicks that were fed herring exclusively and eight of the 10 chicks fed a mixed diet (herring and salmonids) died, whereas all chicks fed only salmonids survived. Renal lesions ranged from mild to marked generalized nephrosis, which was characterized by degeneration and necrosis of the proximal convoluted tubular epithelium and dilation of the distal convoluted tubules and collecting ducts. These observations suggest that fish frozen in brine is unsuitable food for hand-rearing of young herons. PMID- 1417609 TI - The effect of acetone on the viability of chicken anemia agent. AB - To study the effect of acetone on the viability of CAA, a sample of CAA with a known titer was treated with 90% acetone for 24 hours at room temperature. The remaining viable CAA was quantitated by titrating the treated preparation in MDCC MSB1 cell culture. Results indicated that CAA is very resistant to inactivation by acetone. PMID- 1417610 TI - A comparison of the gland of Harder response and head-associated lymphoid tissue (HALT) morphology in chickens and turkeys. AB - The immunofunctional response of the gland of Harder (GH) was compared in chickens and turkeys using an in vivo assay previously developed for use in chickens. The GH were surgically removed (GHx) from leghorn chicks at 1 day of age and from poults at 2 days of age. Intact birds of each species served as controls. During the fourth week of age, both GH-intact and GHx chicks were exposed to killed Brucella abortus antigen by the ocular or intraperitoneal route. One week later, serum and tears were collected and assayed for antibodies to B. abortus. In addition, all birds were killed at the end of the trial period, and the heads were fixed and processed for histologic examination. Various components of the head-associated lymphoid tissue (HALT) including the GH, nasal glands, lacrimal glands, lacrimal ducts, eyelid conjunctiva, and nasal cavity mucosa/submucosa, were evaluated microscopically using a scoring system to estimate quantity and degree of development of immune tissue in those sites. Results of all analyses indicate that functional response and morphology of the HALT are comparable in turkeys and chickens. PMID- 1417608 TI - Serological detection of Mycoplasma synoviae infection in turkeys. AB - The antibody response of turkeys experimentally infected with Mycoplasma synoviae was determined by the serum plate agglutination (SPA), hemagglutination inhibition (HI), and microagglutination (MA) tests and the enzyme-linked immunosorbent assay (ELISA). No antibody response was detected until 2 weeks postinfection (PI) with the MA test (17% positive), 3 weeks PI with the SPA test (11% positive), 4 weeks with the HI test (21% positive), and 5 weeks PI with the ELISA, and even then, only 16% of the birds were positive. Although at least 89% of the birds were positive by culture, only 58% of the turkeys developed a detectable antibody response. PMID- 1417611 TI - Recurrent transient paresis in a turkey flock. AB - Recurring episodes of extreme leg weakness and associated mortality were documented in a turkey flock at 8 to 15 weeks of age. Flock mortality attributed to posterior paresis was approximately 12%, or 4800 of 40,000 turkeys. Four of six open-confinement units were affected. Gross and histological examinations revealed no significant lesions. Immunology and virology were uninformative. There were no significant differences in serum chemistry between clinically affected and normal turkeys. Testing of feed, water, soil, and tissues revealed no common toxicants. Isolation and supportive care for affected turkeys, both in the laboratory and in the field, frequently resulted in full recovery. Injection of a test group of affected turkeys with Type C botulism antitoxin appeared to enhance recovery. However, repeated attempts to detect botulism toxin in serum, liver, or cecal contents using mouse bioassay procedures were unsuccessful. PMID- 1417612 TI - Salmonella enteritidis infection in two species of psittaciformes. AB - In 1990, Salmonella enteritidis phage type 4 was recovered from two young (less than 20-week-old) lilac-crowned Amazon parrots (Amazona finschi Schlater), one in Tennessee and one in Kansas. The parrot from Tennessee was treated for a plugged naris and anorexia before the S. enteritidis infection was discovered. The parrot from Kansas exhibited signs of septicemia and died within 24 hours of examination. An apparently healthy green-cheeked conure (Pyrrhura molinae) on the same premises as the parrot from Tennessee was positive for S. enteritidis phage type 4 on a cloacal swab. These are the first reported cases of avian infection with S. enteritidis phage type 4 in the United States. Because several infectious agents were present simultaneously in the Amazon parrots, it was difficult to determine the precise role of S. enteritidis phage type 4 in the clinical presentations. PMID- 1417613 TI - Epizootiological investigation of an outbreak of pullorum disease in an integrated broiler operation. AB - An integrated broiler company experienced a major outbreak of pullorum disease during 1990. The outbreak resulted in the distribution of Salmonella pullorum infected birds to more than 150 roaster flocks in five states. Twenty-two parent (multiplier) breeder flocks became infected. An epizootiological investigation uncovered a grandparent male line breeder flock as the index flock supplying males to the affected parent flocks. Transmission apparently occurred vertically through the egg and horizontally by contact in the hatcheries and by placement of chicks on contaminated litter. PMID- 1417615 TI - Breeder turkey hens seropositive and culture-negative for Mycoplasma synoviae. AB - Four flocks of clinically normal turkey breeder hens were shown to have suspect and positive Mycoplasma synoviae (MS) hemagglutination-inhibition (HI), enzyme linked immunosorbent assay, and, in some cases, serum plate agglutination serology in the absence of MS isolation. In all cases, HI serology for Mycoplasma gallisepticum (MG) and M. meleagridis was negative. Acholeplasma laidlawii was isolated from some hens in each of these MS-seropositive culture-negative flocks. Immunoblotting was used to help determine if this positive MS serology was a result of cross-reactive antibodies to A. laidlawii or to some other Mycoplasma species. When sera from two of the flocks were reacted with MS antigen in immunoblotting, a strong and characteristic MS immunoblot profile was seen. Immunoblotting gave no evidence of a strong antibody response to A. laidlawii, M. iowae, or MG. This suggests the presence (or earlier presence) of MS in these flocks that is difficult to isolate by routine methods. Furthermore, this work shows that immunoblotting can be an important tool in the diagnosis of poultry diseases. PMID- 1417614 TI - Association of cecal spirochetes with pasty vents and dirty eggshells in layers. AB - Feces-stained eggshells, diarrhea, and typhlitis were identified in two commercial laying flocks in Ohio. Hens with diarrhea had spirochetes in cecal lumina and crypts. On culture, the spirochetes were motile and non-hemolytic, did not produce indole, had 12 to 15 axial filaments, were 9.2 to 11.7 microns in length and 240 to 370 nm in diameter, and had a wavelength of 5.1 to 6.5 microns on transmission electron microscopy. PMID- 1417616 TI - Necrotic enteritis in turkeys. AB - Three flocks of turkey hens (16,000 each) between 7 and 12 weeks of age experienced outbreaks of necrotic enteritis. Necropsy revealed a dilated duodenum and jejunum with mucosal surfaces covered with a diphtheritic membrane. Intestinal scrapings showed very few oocysts of Eimeria sp. Histopathological findings were compatible with necrotic enteritis but with deeper, more severe lesions than in broiler chickens. Clostridium perfringens was isolated by anaerobic culture from the intestinal contents. Mortality returned to normal after ampicillin or tetracycline was added to the drinking water. PMID- 1417617 TI - Intestinal adenocarcinoma of the ileocecal junction in a chicken. AB - An 89-week-old male chicken was presented with signs of depression, emaciation, and weakness. At necropsy, a stricture was found at the ileocecal junction that resulted in blockage and dilation of the ileum proximal to the stricture. Histologically, neoplastic epithelial cells that contained mucin had invaded the intestinal wall and produced a fibrous connective tissue reaction. The lesion was diagnosed as scirrhous intestinal adenocarcinoma. PMID- 1417618 TI - Severe mortality in broiler chickens associated with Mycoplasma synoviae and Pasteurella gallinarum. AB - Severe economic loss due to high mortality and condemnation rates occurred on two commercial broiler facilities. Chickens had moderate-to-severe airsacculitis, pericarditis, perihepatitis, tracheitis, and synovitis. Pasteurella gallinarum was isolated from 16 of 18 pericardia, four of 14 livers, 11 of 16 air sacs, six of seven joints and one of 28 tracheas in pure culture. In addition, Mycoplasma synoviae was isolated from trachea and air sac. Lesions were suggestive of an Escherichia coli septicemia, but E. coli was isolated from only four of 28 tracheas and one of 14 livers in pure culture. A coronavirus was isolated from trachea and lung. Whether this coronavirus represented a vaccine or field strain of infectious bronchitis was not determined. These findings suggested that the severe lesions were due to a concomitant infection with an atypical strain of P. gallinarum. PMID- 1417619 TI - Eastern equine encephalitis in a flock of emus (Dromaius novaehollandiae). AB - Eastern equine encephalitis (EEE) was diagnosed in a flock of emus in southeastern Louisiana. The outbreak involved juvenile and adult breeders ranging in age from 20 to 36 months, with an attack rate of 76% and a case fatality rate of 87%. The diagnosis was confirmed by isolation and characterization of the viral agent, and by detection of EEE antibody in two recovered emus. High mortality was preceded by marked depression, hemorrhagic diarrhea, and emesis of blood-stained ingesta. On postmortem examination, hemorrhagic enteritis and multiple petechia of viscera were observed. Microscopic changes included severe necrosis of hepatocytes, intestinal mucosa, and necrotizing vasculitis of the spleen and lamina propria of the intestine. No nervous system lesions were observed. This outbreak occurred concurrently with EEE in horses and was attributed to unseasonably heavy rainfall with an abundance of arthropod vectors and proximity to free-living reservoir host species. PMID- 1417620 TI - Survey of clinical psittacine bird sera for Salmonella typhimurium agglutinins. AB - Of 2407 serum samples from various kinds of psittacine birds submitted for Chlamydia serology, 2343 (97.4%) were negative, 25 (1.0%) were equivocal, and 39 (1.6%) were positive for Salmonella typhimurium agglutinins. In additional serum samples from two groups of African gray parrots, the prevalence of agglutinins was 0.0% (0/38) in the Timneh variety and 24.0% (6/25) in the Congo variety. In sera from one macaw, one cockatoo, and one Amazon parrot, which were negative for chlamydial antibody activity, there were strongly reactive agglutinins for S. typhimurium. Two Amazon parrots had antibody activity against Salmonella and Chlamydia antigens. PMID- 1417621 TI - Ectopic egg yolk in the abdominal cavity of a cockatiel. AB - A mature cockatiel was presented to the teaching hospital with acute, severe dyspnea and a markedly enlarged abdomen. The bird died 2 hours after admission and was necropsied. A 3-cm egg yolk was present in the abdominal cavity and caused cranial displacement of the abdominal viscera. Death occurred acutely and was probably due to severe respiratory distress. PMID- 1417622 TI - Sex and gender and the impaired therapist. AB - A brief review of the problem of impaired therapists is followed by a more comprehensive review of sexual relationships arising in and following psychotherapy. The prevalence of this latter problem is approximately 10%. Offenders are predominantly male, one half are said to be "ruthless" and "exploitative", whilst the remainder are often "lovesick". The author relates these phenomena to processes of repudiation of the relational/feminine self of the highly masculinised clinician. Characteristics of offenders and consequences for patients are presented and issues of detection, sanctions, legislation, and prevention are addressed. Studies suggest that the vast majority of patients are harmed by the experience and that neither improved training, licensing, personal therapy, nor supervision of therapists will guarantee against its occurrence. PMID- 1417623 TI - Empathy--a retrospective on its development in psychotherapy. AB - The paper situates the notion of empathy broadly within the historical context of its origins and subsequent conceptual development, particularly in psychotherapy. It shows how the term is related to its wider usage in popular culture and in studies outside of psychoanalytic psychotherapy. The paper surveys the contributions of several psychoanalytic writers, from Freud to Kohut. This is followed by a critique of more recent psychoanalytic inquiries into empathy. The discussion explores reasons for some of the difficulties resting with a psychoanalytic approach. It is suggested that these are due in large measure to inherent difficulties in defining the term, but that they are accentuated by the language and polemics of psychoanalysis. More specific contributions are considered with a view to understanding the notions of aetiology, description, function and epistemology in regard to empathy within the psychoanalytic framework. PMID- 1417624 TI - Clarification of values in counselling and psychotherapy. AB - When an individual acts contrary to personal values, then there is dissonance, with consequences of guilt, anxiety, despair, or alienation. If unresolved and of sufficient strength these feelings may manifest in mental illness. Thus, clarification of values and resolution of value conflict are relevant to counselling and psychotherapy. A framework for the systematic examination of values in therapy is described. Values are classified as personal, social, environmental and sensate. In therapy, goals may be matched for congruence between personal values and overt behaviour. Processes which erode values and ways to maintain integrity of personal value systems are considered. PMID- 1417625 TI - Adult attachments and sexuality: implications for understanding risk behaviours for HIV infection. AB - In response to the AIDS epidemic, there has been an intensification of interest in human sexuality research in general and "safe sex" practices in particular. Most research models have been somewhat mechanistic in focus, however, with little recognition of the significance of affectional needs in the formation and maintenance of sexual relationships. In this paper we propose that relationship issues are central to an understanding of the expression of sexuality, and that attachment theory provides a useful perspective on human sexual bonds. It is suggested that future research could usefully extend the conceptualisation of adult attachment styles by exploring the meaning of attachment relationships for gay and heterosexual couples, and the implications of attachment style for the behaviours associated with sexual relationships, including the negotiation of safe sex practices. Such research would have direct relevance for prevention programs relevant to HIV/AIDS. PMID- 1417626 TI - Attributions of symptomatology: an exploration of family factors associated with expressed emotion. AB - This study explored family factors associated with Expressed Emotion (EE) in families with a member diagnosed with schizophrenia. Drawing on an attributional model of expressed emotion it was predicted that high EE relatives would have less knowledge of the illness and would attribute negative symptoms to the personality, rather than the illness, of the sufferer. Thirty-one caregivers of schizophrenic patients were interviewed. Results indicated that EE status was related to knowledge, coping and causal attributions of negative symptoms. Low EEs, as compared with High EEs, tended to have more knowledge of the illness and to cope better with the patient, and were less likely to attribute the cause of negative symptoms to the sufferer's personality. Support was therefore obtained for the utility of an attributional model in attempting to understand the determinants of levels of EE. PMID- 1417627 TI - Long term secure care in Tasmania. AB - The aim was to determine the requirement in Tasmania for long term (greater than 28 days) secure ward beds, and to characterise the patients who use them. There was complete enumeration over an 18 month period. The results included that 3.6 long term secure beds were used per 100,000 general population. Compared to those who were discharged during the survey, those who were not discharged were older, had spent longer in psychiatric hospitals and were more likely to be male and to suffer from schizophrenia. All patients were white Australians. The conclusions included that for planning purposes a minimum of 4.6 long term secure beds was required per 100,000 general population. Also, Aboriginal people and people from non-English speaking backgrounds were not over represented in long term secure care in Tasmania. Finally, "good" and "poor" prognosis groups were identified and further work is required to determine how these can best be managed. PMID- 1417628 TI - Is tardive anorexia a discrete diagnostic entity? AB - A study is described in which patients in three diagnostic groups were compared in an effort to delineate features of tardive anorexia (late onset anorexia nervosa). There were 18 patients in each diagnostic group. Patients with "classical" anorexia nervosa of less than 5 years duration were compared with patients older than 25 who had been chronically ill for more than 5 years and with those in whom the symptoms had begun de novo after the age of 25. Statistically significant differences were found to distinguish the third group as a distinct diagnostic entity. The association of loss precipitants and depressive symptoms has practical implications in the management of true anorexia tardive. PMID- 1417629 TI - Attitudes of medical professionals towards patients with eating disorders. AB - A questionnaire examining attitudes to patients with eating disorders was completed by 352 medical and nursing staff in a general hospital. Patients with eating disorders were less liked than patients with schizophrenia and were seen as responsible for their illness almost to the same degree as recurrent overdose takers. Factor analysis showed a first factor in which patients with eating disorders were construed as vulnerable to external pressures (from others, the media) while also self-inducing their illness, and this was associated with treatment recommendations for education, urging the patient to take self-control and psychotherapy. The professions differed significantly in attitudes. PMID- 1417630 TI - Knowledge and compliance towards lithium therapy among Chinese psychiatric patients in Hong Kong. AB - Although patient education is believed to promote medication compliance, the exact relationship between the acquisition of drug knowledge and compliance during lithium treatment is unclear. A survey of 50 Chinese patients on maintenance lithium therapy revealed that their medical knowledge about lithium treatment, as measured by a "Lithium Questionnaire," was very limited. Nonetheless, 70% of these patients were found, by multiple criteria, to be good compliers, and lithium compliance was apparently not affected by the amount of drug knowledge that patients possessed. It is argued that in the process of conducting patient education to enhance lithium compliance, a sound therapeutic alliance is more important than sheer knowledge acquisition. PMID- 1417631 TI - The first lithium clinic in Hong Kong: a Chinese profile. AB - A study of 50 Chinese patients referred to the first lithium clinic in Hong Kong revealed a high prevalence of recurrent mania and rarely unipolar depression. A history of delusions and hallucinations, and re-diagnosis from schizophrenia to manic depressive psychosis, were common. Lithium was prescribed after 3.9 episodes of illness, and at a dosage of 1,191 mg despite a moderate serum level of 0.63 mmol/l. Laboratory monitoring was haphazard, and polypharmacy was common. This might pose unnecessary risks to some patients. PMID- 1417632 TI - An Australian multicentre study of moclobemide versus amitriptyline in the treatment of depression. AB - This paper reports the results of a multicentre study of the new monoamine oxidase inhibitor, moclobemide, in the treatment of major depression. Moclobemide is a specific monoamine oxidase-A inhibitor which does not bind irreversibly to the enzyme, unlike the currently available MAOIs. Recent studies would suggest that in subjects taking moclobemide blood pressure elevation caused by tyramine is significantly less than that induced by the irreversible MAOIs, particularly when tyramine is administered in an oral form. Forty-eight patients with major depression were randomly allocated to treatment with either moclobemide or amitriptyline for 4 weeks in a double-blind comparison. There were no statistically significant differences between the two groups on measures of efficacy. Patients taking amitriptyline reported a greater number of side-effects and more patients in the amitriptyline group dropped out because of these. There were no reports of interactions with tyramine-containing foods. PMID- 1417633 TI - Psychiatric morbidity in a Chinese primary school in Hong Kong. AB - The psychiatric morbidity among 718 Chinese primary school children from a lower middle social class area in Hong Kong was studied, using a two-stage design. The screening procedures included two parts, a multi-component scale and a battery of probing questions. The screening procedures achieved an overall sensitivity of 75% and a specificity of 97%. The findings on prevalence were: (i) a total prevalence of all definite psychiatric cases of 16.3%; (ii) prevalence according to diagnostic categories: emotional disorder, 8.8%; conduct disorder, 2.0%; mixed disturbance of emotion and conduct, 3.0%; hyperkinetic syndrome, 1.0%; hyperkinetic conduct disorder, 1.0%; and Gilles de la Tourette's syndrome, 0.4%; (iii) boys 2.7 times more affected than girls; (iv) emotional disorder much more common than conduct disorder, even in boys; and (v) the prevalence of borderline cases was 19.5%. The mean duration of morbidity for all definite cases was 41.7 months. About half of all definite cases were seriously impaired in one or more areas of functioning and the other half moderately impaired. These results were compared with findings obtained from studies done in other countries. PMID- 1417634 TI - A study of referrals of black children to a general hospital psychiatric outpatient clinic. AB - Five hundred and seventy-seven children who attended a child psychiatric out patient clinic during 1987 were evaluated. Their clinical and demographic characteristics are described and management discussed. High on the list of presenting complaints were poor school performance and behavioural problems. Factors considered as influencing referrals are socio-economic, political, lack of school psychological services and facilities for the management of the intellectually handicapped. The most common diagnoses were mental retardation (39.5%) and epilepsy (16.2%). PMID- 1417635 TI - Serious suicide attempts among adolescents in custody. AB - The Royal Commission into Aboriginal Deaths in Custody has focused attention on people who are held in custody in police cells, prisons, remand centres and detention centres. A series of research papers has been released by the Royal Commission which delineates some important aspects of the needs of these people. Nearly half of the deaths which occur in these custodial settings appear to be self-inflicted. Suicide seems to be particularly common among younger age groups of those in custody [1,2]. This pattern parallels suicide levels among young people in the Australian community generally, so that suicide is now a leading cause of death among young Australians [3,4]. PMID- 1417636 TI - The psychological adjustment of offspring of adults with obsessive-compulsive disorder: a brief report. AB - This study describes the prevalence of emotional and behavioural problems in the offspring of parents who are members of the Obsessive-Compulsive Neurosis Support Group in South Australia. The results suggest that the offspring of adults with obsessive-compulsive disorder do not have more problems than other children and adolescents in the community. The study also highlights potential benefits of collaborative research conducted by research groups and self-help organisations. PMID- 1417637 TI - Social networks and psychiatric morbidity in New Zealand women. AB - A random community survey of urban and rural New Zealand women revealed higher rates of psychiatric morbidity in subjects who reported poorer social support. Substantial differences in social networks were found between demographic subgroups. Rural women described better than expected social relationships, giving some support to the pastoral ideal of well integrated rural communities. Women in part-time employment also described better social networks. Elderly, low socio-economic, and widowed, separated and divorced women had poorer social relationships. It is suggested that normative values for social network measures for each demographic subgroup will need to be established before the clinical significance of deviations from the norm can be meaningfully evaluated. Also, the mechanisms linking social networks to health may vary in different subgroups. PMID- 1417638 TI - Quantity frequency (consumption index) versus "CAGE" in the detection of alcoholism. AB - The aim of this study was to compare and validate two simple methods of detecting excessive alcohol drinkers in a Malaysian hospital population. All 621 patients in the Medical, Surgical and Orthopaedic units of the General Hospital Kuala Lumpur were screened with the "CAGE" Questionnaire (a four question screening test to discriminate excessive drinkers) and two questions on the frequency and quantity of drinking called the Consumption Index. All CAGE scores had poor agreement (K = 0.37 to K = 0.1) with a psychiatric diagnosis of alcohol abuse and dependence using DSM III diagnosis. Reasons why the Consumption Index is a better screening instrument than the CAGE are discussed. PMID- 1417639 TI - A community study of mental disorders in elderly Singaporean Chinese using the GMS-AGECAT package. AB - A random sample of 612 elderly Chinese aged 65 and over living in the community in Singapore was assessed with the community version of the Geriatric Mental State (GMS) and the data analysed by the AGECAT program to provide computerised diagnoses. The prevalence of organic disorder (dementia) was 2.3%, depression 5.7%, neuroses 1.5% and paranoid disorder 0.5%. The results were generally lower compared to the study of elderly people in Liverpool using the GMS-AGECAT package. Concordance between AGECAT and the psychiatrist's diagnoses for organic disorder, depression, neuroses and paranoid disorder achieved kappa values of 0.87, 0.88, 0.58 and 1.0 respectively. PMID- 1417640 TI - Diffuse Lewy body disease and progressive dementia in a young woman. AB - This report details the emergence of a progressive parkinsonian syndrome, dementia and behavioural disturbance in a 33 year-old woman which can be dated to the delivery of her first child. The findings of this case indicate that cortical Lewy body disease should be considered in any patient with temporoparietal dementia and idiopathic Parkinson's disease irrespective of the age of onset. PMID- 1417641 TI - Clinical psychologists and the college's view. PMID- 1417642 TI - Senior trainees and new consultants group. PMID- 1417643 TI - Language and complex phenomena. PMID- 1417644 TI - Consent and treatment. PMID- 1417645 TI - Definitions and defining responsibility. PMID- 1417646 TI - Effects of 2 mg and 4 mg atropine sulfate on the performance of U.S. Army helicopter pilots. AB - Atropine autoinjectors are issued to aviators for use in the event of organophosphate poisoning on the battlefield. This investigation assessed the effects of unchallenged 2 mg and 4 mg doses on flight performance, vision, tracking, cognitive performance, and electroencephalograms of 12 Army aviators. Effects were seen most often with the 4 mg dose in terms of aircraft control problems, vision disturbances, impaired tracking, reduced cortical activation, and decreased cognitive skill. These problems indicate helicopter tactical flight is dangerous after an unchallenged 4 mg dose. Other types of flight should also be avoided for at least 12 h after atropine. PMID- 1417647 TI - Subjective and behavioral effects associated with repeated exposure to narcosis. AB - Below 30 m, nitrogen narcosis can severely degrade the performance of air breathing divers. Within the diving community it is generally thought that this effect can be reduced by repeating deep air dives on successive days but laboratory studies have found no strong evidence to support the notion of adaptation to narcosis. One possible explanation for this discrepancy is that one's subjective impression or perception of narcosis may decrease during repeated exposure to hyperbaric air without parallel improvement on task performance. To examine this possibility, symptoms and performance were examined over the course of 5 days of repeated exposure to 30% nitrous oxide at 1 ATA. While the results revealed no clear cut changes in global perceptions of narcosis across days, several symptoms from an adjective checklist showed unequivocal signs of adaptation. With respect to performance effects, reaction time yielded no indications of improvement over days relative to the control. These findings suggest that subjective adaptation can occur without parallel performance improvement, an effect which could compromise safety and which may be of concern in other operational settings that involve repeated exposure to stimulus conditions which impact on performance and symptoms. PMID- 1417648 TI - Comparison of toxicity rankings of six aircraft cabin polymers by lethality and by incapacitation in rats. AB - Polymeric aircraft cabin materials have the potential to produce toxic gases in fires. Lethality (LC50) in animal models is a standard index to rank polymers on the basis of their combustion toxicity. However, the use of times-to incapacitation (ti) may be more realistic for predicting relative escape times from a fire. Therefore, LC50 and ti for polymers, polyamide (I), polystyrene (II), Nylon 6/6 (III), polysulfone (IV), polyethylene (V) and chlorinated polyethylene (VI), of different chemical classes were determined and compared. Male rats, 12/fuel loading, were exposed to the pyrolysis products from selected weights of each polymer for 30 min in a 265-L combustion/exposure system, and LC50 values were determined following a 14-d observation period. For each polymer, ti was measured at 16 g and at its respective LC50 using the inability of rats (n greater than or equal to 12) to walk in rotating cages as a criterion for incapacitation. LC50 (45.7-87.5 mg/L) of the polymers had the order of I less than II approximately III less than IV less than V less than VI, while their ti (6.6-21.1 min) at 16 g (60 mg/L) had the order of III approximately I less than V approximately II less than VI less than IV. Based on ti at LC50, polymers were grouped into III & V; I, II & VI; and IV. LC50 and ti did not exhibit the same relative toxic hazard rankings for these polymers; ti were also not equal at the LC50 concentrations. These findings demonstrate the possible involvement of different mechanisms of action for the combustion products of these polymers at the selected end points. PMID- 1417649 TI - Reduced voluntary non-visual suppression of the vestibulo-ocular reflex gain during nitrous oxide narcosis. AB - The effect of subanesthetic nitrous oxide (N2O) narcosis (21%) on the vestibulo ocular reflex (VOR) and on voluntary non-visual suppression of the VOR was studied in 12 subjects, using a velocity step rotational test. Gain and time constant of the VOR were calculated by computer. During tests, the subjects were required either to perform mental arithmetic or to attempt to follow an imaginary target rotating with them in the dark. Voluntary non-visual suppression of gain was significantly reduced during exposure to N2O, though there was no statistically significant effect of N2O on gain per se. The time constant was unaffected either by voluntary suppression or by N2O. The reducing effect of N2O on voluntary non-visual suppression of VOR gain is assumed to be due to reduced alertness. Reduced voluntary non-visual suppression of VOR may imply reduced visual-vestibular interaction, which might be one explanation of the complaints of dizziness associated with fatigue or with ingestion of certain sedatives. PMID- 1417650 TI - Heat strain during at-sea helicopter operations and the effect of passive microclimate cooling. AB - Twelve Navy H-3 helicopter aircrew members were monitored (heart rate, skin and rectal temperatures) in both microclimate cooling (ice) vest and non-vest conditions during at-sea operations in the high heat environment of the Persian Gulf. During all flights and flight phases, ambient dry bulb temperatures ranged from 31.0 degrees C (in-flight) to 48.6 degrees C (hover). Heart rate was greatest during hover and on-deck (range: 89.9 to 145.0 beats/min) without an ice vest, yet was significantly reduced with ice (range: 79.7 to 86.0 beats/min) (p less than 0.05). Rectal temperature was not found to be different between vest and non-vest conditions; however, change across flight phases in both conditions was significant (p less than 0.05). Analysis of variance demonstrated significantly lower mean weighted skin temperatures (p less than 0.05) when wearing the ice vest. These data suggest that wearing a protective cooling vest can reduce the heat strain associated with helicopter flight in high heat environments. PMID- 1417651 TI - Thermal convergence fails to predict heat tolerance limits. AB - Work under very hot, humid conditions may raise skin temperature (Tsk) to meet rectal temperature (Tre). This convergence has been said to produce imminent collapse and therefore to predict human tolerance limits for work in heat, especially for those wearing impermeable protective clothing. The purpose of this study was to examine the ability of subjects to continue work beyond the time when they experienced convergence. A total of 15 healthy adult volunteers participated in two protocols: A) Each of nine subjects performed four experiments wearing impermeable clothing and walking on an inclined treadmill at a metabolic rate averaging 450 W with dry bulb temperature (Tdb) 29 or 38 degrees C; B) Each of nine subjects performed eight experiments wearing heavy, semipermeable clothing under a range of conditions involving Tdb = 22-40 degrees C, relative humidity 15-88%, and work load = 200-500 W. Convergence occurred in 42 cases; in the majority (60%) the subject continued walking until Tre rose to the criterion temperature 39 degrees C, working for 10-45 min after convergence. No subject approached collapse, nor did convergence have any special effect on the rate of rise of temperature or heart rate. Thus, while convergence marks severe, time-limited heat stress, it does not accurately predict tolerance limits in highly motivated subjects. Termination of work at convergence would unnecessarily truncate heat stress exposures, depriving investigators of valuable data and industrial users of a large portion of their safe work time. PMID- 1417653 TI - The influence of prior exercise at anaerobic threshold on decompression sickness. AB - This study was conducted to examine the effects of exercise prior to decompression on the incidence of altitude decompression sickness (DCS). In a balanced, two-period, crossover trial, 39 healthy individuals (29 males, 10 females) of mean (S.D.) age 32.5 (7.7) years and body mass index 23.7 (3.4) were each exposed twice, without denitrogenation, to an altitude of 6,400 m (21,000 ft) in a hypobaric chamber. Under the experimental condition, subjects exercised at their predetermined anaerobic threshold levels for 30 min each day for 3 d prior to altitude exposure; the other condition was a non-exercise control. Under both conditions, subjects performed exercise simulating space extravehicular activities at altitude for a period of 3 h, while breathing 100% oxygen. There were nine preferences (untied responses) for DCS, four under control and five under experimental conditions; all were Type I, pain-only bends. No carryover effect between exposures was detected, and the test for treatment differences showed p = 0.56 (95% confidence interval = 0.34-0.58) for symptoms. No significant difference in DCS preferences was found after subjects exercised up to their anaerobic threshold levels during the days prior to decompression. PMID- 1417652 TI - Effects of hypoxemia at sea level and high altitude on sodium excretion and hormonal levels. AB - Acute hypoxemia at sea level is associated with decreased aldosterone secretion. This inhibition is thought to be mediated through secretion of atrial natriuretic factor (ANF). The interaction of these two hormones should result in enhanced renal salt excretion during hypoxemic conditions. This hypothesis was tested by administration of a standardized salt load to seven normal subjects during normoxemia at sea level (SL), acute hypoxemia (AH) at sea level, and high altitude (HA) (3,000 m). Urine and venous blood samples were collected and analyzed. A natriuresis and diuresis was observed only under AH conditions. It was accompanied by a decrease in plasma aldosterone levels, but did not correlate with changes in plasma aldosterone levels, ANF, or other hormones. Increased plasma renin activity (PRA) and increased norepinephrine levels were encountered at HA, suggesting sympathetic nervous system activation. No change in anti diuretic hormone (ADH) levels with increased plasma osmolality was seen at HA. We conclude that excretion of a salt load during normobaric hypoxemia is enhanced by a decrease in plasma aldosterone levels, unrelated to changes in ANF or other hormones. The differences observed in norepinephrine, PRA, and ADH levels during HA versus AH conditions suggest that hypobaria or chronic hypoxemia may influence these hormonal responses. PMID- 1417654 TI - An assessment of Turkish Air Force pilots' anxiety and depression levels. AB - A popular conception of good morale is the perception of well-being, lack of distress, and absence of anxiety and depression. Therefore, the term "morale" is related to anxiety and depression. The purpose of this survey is to assess stress levels numerically by using anxiety and depression scores. We surveyed 345 active duty Turkish Air Force pilots and 70 non-flying Air Force officers (who served as control group) in 1988. Spielberger's State Trait Personality Inventory (STPI-A Trait) and Zung's Depression Scale (ZDS) were applied to both groups. The flier group reflected lower scores than the non-fliers. Different explanations are available, but we believe the most likely to be related to higher motivation and job satisfaction as well as ego strengths of fliers. These factors can increase the ability to cope with stressful conditions. PMID- 1417655 TI - Assessing for preflight predictors of airsickness. AB - A total of 57 randomly selected male and female student pilots from an Introduction to Aviation private pilot course in a large aviation program of a midwestern university completed this study. These pilots were assessed for health status and surveyed for airsickness and associated symptoms by use of an Airsickness Inventory Questionnaire developed by the authors and a modified Self Rating Anxiety Status Inventory Scale tool developed by W. K. Zung. Correlational analyses of scores from self-report inventories were used to evaluate strength of relationships between airsickness and anxiety. Multiple linear stepwise regressions were computed on variables of correlated symptoms for predictiveness of airsickness. Results of the study indicated 28.1% of pilots exhibited symptoms of airsickness. Significant correlations indicated moderate relationships between airsickness and the following preflight indicators: nausea and vomiting, tremors, face flushing, nightmares, urinary frequency, excessive nervousness, and anxiety index. PMID- 1417656 TI - Spatial disorientation and dysfunction of orientation/equilibrium reflexes: aeromedical evaluation and considerations. AB - Loss of spatial awareness has been implicated as a direct causal factor in 4-10% of serious aircraft mishaps and 10-20% of fatal aircraft mishaps (7). Spatial disorientation in flight usually results from misperception of visual, vestibular, or proprioceptive cues. Pathologic causes have rarely been implicated. A student naval aviator with recurrent loss of spatial awareness due to a defective vestibulo-ocular reflex (VOR), presumably from vestibular neuronitis in adolescence, is reported. His chief complaint, an inability to focus on the instrument panel during turbulent instrument meteorological conditions (IMC), resulted in spatial disorientation and adverse flight attitude. A simple test of visual-vestibular interaction, the dynamic visual acuity test, could identify a defective vestibulo-ocular reflex in aviation personnel. An absent or defective vestibulo-ocular reflex has potential for disorientation in instrument flight. A comprehensive vestibular function test battery is indicated in individuals with recurrent or overwhelming spatial disorientation who fail a screening dynamic visual acuity test. The aeromedical disposition of vertigo and dysequilibrium is discussed. PMID- 1417657 TI - Cortical localization of cognitive function by regression of performance on event related potentials. AB - This paper demonstrates a new method of mapping cortical localization of cognitive function, using electroencephalographic (EEG) data. Cross-subject regression analyses are used to identify cortical sites and post-stimulus latencies where there is a high correlation between subjects' performance and their cognitive event-related potential (ERP) amplitude. The procedure was tested using a mental arithmetic task and was found to identify essentially the same cortical regions that have been associated with such tasks on the basis of research with patients suffering localized cortical lesions. Thus, it appears to offer an inexpensive, noninvasive tool for exploring the dynamics of localization in neurologically normal subjects. PMID- 1417658 TI - Documentation of activity and rest of a U.S. National Guard attack helicopter battalion. AB - A. U.S. National Guard attack helicopter battalion was monitored in order to document the activity and rest obtained during the annual training exercises. A total of 39 soldiers wore wrist activity monitors during the 2-week training period. The data from these monitors discriminate activity from rest. Results indicated the following: 1) at some point during the exercises, everyone became sleep deprived; 2) the participants who received the most rest of the group were the enlisted headquarters personnel and the pilots; 3) the soldiers who received the least amount of sleep were the commander of the battalion and the maintenance personnel. Some recommendations are offered for future planning of National Guard training exercises. PMID- 1417660 TI - Aerospace Medical Association. Directory issue. 1992. PMID- 1417659 TI - Effect of the prelaunch position on the cardiovascular response to standing. PMID- 1417661 TI - Detection of early xerophthalmia by impression cytology and rose Bengal staining- a comparative study. AB - Twenty two cases were studied for early detection of Xerophthalmia by impression cytology and Rose Bengal staining. Patients were below 6 years of age and admitted in the paediatric ward of Dhaka Medical College Hospital. Assessment were done by conjunctival impression cytology and staining with 1% Rose Bengal dye. Estimation of serum retinol level was done by HPLC to correlate conjunctival findings with biochemical status. The mean age of the subjects were 3.15 +/- 1.75. Rose Bengal staining was positive in 40% cases and impression cytology was in 60% cases. The mean serum retinol level of the diseased children were 10.5 +/- 3. ug/dl. The sensitivity of Rose Bengal staining was 53.3% and that of impression cytology was 80% in detecting vitamin A deficiency when compared with serum retinol level. The specificity of Rose Bengal staining was 40% and that of impression cytology was 100%. Sensitivity of impression cytology was 100% in patient with retinol level 10 ug/dl. PMID- 1417662 TI - Studies on virulence determinants of Plesiomonas shigelloides. AB - Virulence determinants of nineteen strains of Plesiomonas shigelloides isolated from stool samples of diarrhoeal children were studied. Heat-labile toxin was detected in seven strains using rat ileal loop model and in none of the strains using Chinese hamster ovary cell assay system and by Enzyme-linked immunosorbent assay. Rat ileal loop model was used for the first time to assay toxin in P. shigelloides and is suggested to be a cheap and effective method of detecting labile toxin in the organism. Heat stable toxin, cytotoxin, hemolysin and hemagglutinin were not detected in the strains tested. Invasiveness could not be established by using HEp-2 cell assay system. The results of this study provide some experimental support for an etiological role for P. shigelloides in the production of diarrhoea. PMID- 1417664 TI - Plasma ascorbate status in newly diagnosed diabetics exhibiting retinopathy--a finding that alarms. AB - Diabetics, who developed retinopathy within one year of detection of disease were found to have a significantly low plasma total ascorbate concentration compared to those who developed retinopathy 7-17 years after detection of DM. Traditional metabolic parameters did not show significant difference between the two groups. Thus a severe ascorbate deficiency may be an important determinant in the pathogenesis of retinopathy independent of metabolic status and duration of DM. It merits early supplementation of ascorbic acid to retard the progression of microvascular complication. PMID- 1417663 TI - Factors influencing development of bulbar deformity in duodenal ulcer disease. AB - Sixty subjects were carefully interrogated and repeatedly endoscoped with a view to studying the effect of sucralfate on healing and recurrence of duodenal ulcer disease. Degree of bulbar deformity was noted during each endoscopy. During the trial it appeared that deformity progressed more rapidly in late onset subjects (onset at or above 30 years of age). In eight subjects deformity became gross over a period of three years. Seven of them belonged to the late onset subgroup. Two subject had large ulcers and both belonged to the late onset subgroup, one had rapidly progressive disease. Out of six subjects with multiple ulcers four belonged to the late onset subgroup, two of the later had rapidly progressive disease. PMID- 1417665 TI - Disease profile in respect of health services of Upazila health complex. AB - This study was carried out to identify the disease profile in relation to medical services at upazila health complex. Thirty different types of diseases were identified. Diarrhoeal diseases were found to be highest (53%), the second highest was intestinal worms (44%). About ninety seven percent patient attended the OPD and only 2% were attended in the emergency Department. On average 172 patients were admitted per month and the highest of admission was found in the months of September and October. The average length of stay in the hospital was 11.6 days. Among the patients admitted 55% were male, and 45 were female. 5% pregnant mothers attended in U.H.C. for antenatal checkup and 2% mother were admitted into the hospital after delivery. Metronidazole was the drug of highest consumption followed by B-Complex and Penicillin. PMID- 1417666 TI - Role of vitamin A and E in spondylosis. AB - A biomedical study was undertaken at the Institute of Nutrition and Food Science, University of Dhaka to observe the effect of the antioxidative roles of vitamins A and E on the degenerative process occurring in spondylosis in human. A single and a double blind study were done. Thirty two patients suffering from spondylosis were selected for the study on the basis of certain criteria. The serum vitamin E level in most of the patients were lower (5.8 +/- 2.7 umol/L) than normal (11-41 umol/L). Vitamin E administration at a dose of 100 mg daily for three weeks resulted in a significant increase in serum vitamin E level accompanied by complete relief of pain. The serum vitamin A level of the patients were already within the normal (0.53-2 umol/L) range and vitamin A administration was not effective in relieving the pain. The results therefore strongly indicate that vitamin E is effective in curing spondylosis and most probably due to its antioxidant activity. PMID- 1417667 TI - Scheduled running wheel activity indexes the specificity of pharmacological anorexia. AB - Nondeprived male Sprague-Dawley rats that were given scheduled access to running wheels for 60 min daily ran immediately and energetically. Intraperitoneal injections of 400 micrograms/kg pancreatic glucagon and 0.15 microgram/kg cholecystokinin octapeptide had no effect on scheduled running, but significantly inhibited feeding when the rats were offered condensed milk instead of access to the running wheels. This is consistent with the hypothesized function of these peptides as postprandial satiety signals. In contrast, 0.5 mg/kg amphetamine and 75 microM/kg LiCl, which produced similar degrees of anorexia, inhibited running by about 50%. Amphetamine, but neither peptide, also inhibited water drinking and disrupted the behavioral sequence of postprandial satiety. The distance run during scheduled running tests was inversely related to body weight, but the patterns of the drugs' effects were not altered by baseline running differences. Scheduled wheel running is a robust consummatory behavior that appears to provide a relatively valid, simple, and sensitive test of the behavioral specificity of pharmacological anorexia. PMID- 1417669 TI - Preoperative operant circling training facilitates recovery following unilateral substantia nigra lesion in rats. AB - This study was undertaken to examine (1) whether pre- and/or postoperative training, using water reinforcement, to turn in circles (rotation) affects the behavioral symptoms induced by unilateral 6-hydroxydopamine (6-OHDA)-induced DA denervation of the rat substantia nigra (SN); (2) whether there was any influence of this training on the temporal pattern of recovery; and (3) whether the rotational training influences turning induced by systemic injection of dopaminergic drugs. In the first experiment, rats were trained either ipsi- or contraversive (TI or TO) to the side to be damaged 11 days before and 23 days after lesion, and tested in an open field for rotational behavior following systemic administration of apomorphine and amphetamine. In the second experiment rats were trained only before the lesion was made and tested in the open field for spontaneous circling and thigmotactic behavior. The results of the first experiment indicated maintenance of the training performance after the lesion. At the 14th day after the lesion, the ipsiversive trained group showed a higher contraversive circling frequency after apomorphine injection in relation to the contralateral trained group. In the second experiment, rats trained only before the surgery, showed asymmetrical spontaneous circling in the trained direction before and 14 days after surgery, indicating, in a drug free condition, that training direction can be restored after unilateral SN lesions, even to the contralateral body side. Moreover, thigmotactic behavior indicated a lack of habituation in an open field in unilateral lesion rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1417668 TI - Evidence for separate control of estrous and circadian periodicity in the golden hamster. AB - To study the relationship between estrous and circadian periodicity, we investigated the period of the estrous cycle in two types of female golden hamsters: normals (circadian period approximately 24 h) and tau mutants (circadian period approximately 20 h). Records of running wheel activity, general locomotor activity, body temperature, vaginal secretion, and sexual receptivity of hamsters kept under constant lighting conditions indicated an estrous period of approximately 96 h for both groups of animals. The fact that animals with different circadian periods have the same estrous period suggests the existence of separate mechanisms in the control of circadian and estrous periodicity. Circadian periodicity is determined by a pacemaker located in the suprachiasmatic nuclei, whereas estrous periodicity is determined by positive and negative feedback loops involving the hypothalamus, pituitary, and gonads. Coupling of the two mechanisms takes place under at least some conditions, but additional research is necessary to elucidate the mechanisms by which this is accomplished. PMID- 1417670 TI - The relationship between adrenal steroids and enrichment-induced brain growth. AB - The question of whether brain growth brought about by environmental enrichment is mediated by the adrenal cortex has not been answered. Accordingly, young male rats were either adrenalectomized (ADX) and infused with a constant maintenance dose of corticosterone (2 mg.kg-1.day-1) or sham-operated and implanted with a blank infusion device. Half of each surgical group was maintained in either impoverished (IC) or enriched conditions (EC). After 30 days, changes in forebrain growth and thickness of various cortical and subcortical regions were determined for each group. Enrichment and ADX independently increased forebrain weight and thickened cortical tissue at about the same anatomical sites. However, combined treatments were additive, not interactive. EC-induced brain growth is mimicked but not mediated by adrenalectomy. PMID- 1417671 TI - Microdialysis administration of vasopressin and vasopressin antagonists into the septum during pole-jumping behavior in rats. AB - Wistar rats (n = 95) were trained in a pole-jumping apparatus (10 trials/session/day) to investigate the involvement of centrally and peripherally released endogenous AVP in their acquisition rate and to examine the feasibility of the microdialysis technique for the administration of peptides during a behavioral test. After session 1, a microdialysis probe was implanted into the septum; during sessions 2 and 3 the probe was perfused with artificial cerebrospinal fluid (aCSF) alone or containing either AVP (delivered amount via the probe: 0.2 ng) or the V1 (d(CH2)5Tyr(Me)AVP, 5.0 ng) or the V2/V1 (d(CH2)5-D Tyr(Et)VAVP, 5.0 ng) antagonist. Administration of AVP via microdialysis into the septum failed to alter the acquisition rate of pole jumping. Also, ip application of both hypertonic saline and the AVP V1 antagonist (10 micrograms) in another experiment failed to show a significant effect upon behavior. Septal administration of the V1 or the V2/V1 antagonist via microdialysis, however, produced a significantly impaired performance. The results indicate that AVP release within the septum is involved in the acquisition of pole-jumping behavior probably mediated by the V1 receptor subtype. An additional involvement of the V2 receptor subtype, however, cannot be entirely excluded. The microdialysis technique proved to be a potent tool to administer substances concomitantly with behavioral tests. PMID- 1417672 TI - Increases in dendritic length in occipital cortex after 4 days of differential housing in weanling rats. AB - To assess the capacity for experience to induce rapid alterations in the dendritic fields of cortical neurons, male Long-Evans hooded rats aged 30-31 days were housed in either a complex environment (EC) or an individual cage (IC) for 4 days. The basilar dendrites of layer III pyramidal cells in area 17 of visual cortex were measured in Golgi-stained sections. EC rats exhibited significant increases in total dendritic length and total number of branches. This finding demonstrates that the structural modifications previously reported after 30 days in the complex environment are well underway after only 4 days. PMID- 1417673 TI - Impairment of spontaneous alternation performance by an NMDA antagonist: attenuation with non-NMDA treatments. AB - N-Methyl-D-aspartate (NMDA) receptor antagonists disrupt learning on a variety of tasks. Previous findings indicate that glucose, naloxone, and physostigmine ameliorate learning deficits produced by several treatments. The present experiment examines whether these agents also reverse the amnestic effects of NMDA receptor blockade. Mice were tested for spontaneous alternation performance in a Y-maze. The animals received either saline or the NMDA antagonist, NPC 12626 (35 mg/kg, IP), 50 min prior to testing and received an additional injection of saline, glucose, naloxone, or physostigmine 30 min prior to testing. NPC 12626 significantly decreased alternation scores. Glucose (250 mg/kg), physostigmine (0.01 mg/kg), and naloxone (1 mg/kg) reversed the effects of NPC 12626. Thus, impairments of learning after NMDA receptor blockade share with other amnestic conditions the susceptibility to attenuation by glucose, naloxone, and physostigmine. PMID- 1417674 TI - Chronic sodium azide treatment impairs learning of the Morris water maze task. AB - A reduction in the activity of cytochrome oxidase, a respiratory chain enzyme, has been recently identified in mitochondria from blood platelets and postmortem brain tissue from Alzheimer's disease (AD) patients. We have developed an animal model of this deficit in rats by chronic subcutaneous infusion of sodium azide, a selective inhibitor of cytochrome oxidase, delivered via Alzet 2ML4 osmotic minipumps. In previous work, azide-treated rats were impaired in an appetitively motivated spatial learning task, the radial arm maze. In the present investigation, we tested male Sprague-Dawley rats (350-400 g), which were tonically infused with azide or saline, on an aversively motivated spatial task, the Morris water maze. Azide-treated rats were impaired on both acquisition and retention of this task, without showing evidence of a motor impairment. Thus, the present results are consistent with previous findings showing that chronic azide treatment produces a learning and memory deficit. These findings strengthen the hypothesis that azide treatment in rats produces a useful animal model of some aspects of AD. PMID- 1417676 TI - Selective lesions in the temporal-hippocampal region of the rat: effects on acquisition and retention of a visual discrimination task. AB - The first purpose of this study was to investigate whether lesions in the temporal region may affect acquisition or retention of a discrimination task. In Experiment 1, rats with lesions of the temporal cortex (TC), the lateral entorhinal cortex (LEC), or their interconnections were tested postoperatively in simultaneous brightness discrimination. The results show that neither TC lesions nor LEC lesions affected acquisition of the task, and only LEC lesions impaired retention. TC/LEC transections impaired both acquisition and retention. The second purpose was to investigate effects of hippocampal lesions and perforant path transections on the discrimination task (Experiment 2). Both hippocampal and perforant path lesions impaired acquisition of the task, whereas retention was unaffected. It is suggested that TC and LEC are primarily involved in information storing and that hippocampal function is primarily involved in information processing. PMID- 1417675 TI - Amnesia by post-training infusion of glutamate receptor antagonists into the amygdala, hippocampus, and entorhinal cortex. AB - The blockers of glutamate receptors, aminophosphonovaleric acid (AP5) (5.0 micrograms) and cyano-nitroquinoxaline-dione (CNQX) (0.5 microgram), were infused bilaterally into the amygdala, dorsal hippocampus, or entorhinal cortex of rats through indwelling cannulae 0, 90, 180, or 360 min after step-down inhibitory avoidance training. Animals were tested for retention 24 h after training. In the amygdala or hippocampus, AP5 was amnestic when given 0 min after training and CNQX was amnestic when given 0, 90, or 180 min after training. In the entorhinal cortex, AP5 was amnestic when given 90 or 180 min after training and CNQX had no effect. The results suggest that a phenomenon sensitive first to AP5 and then to CNQX in the amygdala and hippocampus, probably long-term potentiation (LTP), is crucial to post-training memory processing. LTP in these two structures could underlie their role in memory consolidation and could explain the late involvement of the entorhinal cortex in post-training memory processing. PMID- 1417677 TI - An adoption and a cross-fostering study of the Minnesota Multiphasic Personality Inventory (MMPI) Psychopathic Deviate Scale. AB - The first of two complementary studies compared biological and adoptive parents of teenage adoptees with either higher (n = 21) or low (n = 51) MMPI Psychopathic Deviate (Pd) scale scores. In comparison to biological mothers of the low-Pd adoptees, biological mothers of the high-Pd adoptees obtained significantly higher MMPI scores on six of eight clinical scales. Fewer differences existed between the corresponding groups of adoptive mothers, but adoptive mothers of the high Pd's did obtain significantly higher scores on the Pd and Hypomania scales. Substantial genetic correspondences also existed for Harris-Lingoes content subscales, with fewer correspondences between adoptees and their adoptive mothers. There were indications that adoptive mothers of the high-Pd children had personality traits which may have made them less effective in attenuating early signs of antisocial behavior. The second study employed a cross-fostering design dividing all biological and adoptive mothers (n = 138 each) by their respective median Pd raw scores to examine effects on offspring. Results confirmed the effect of biological mother Pd score, but only a trend suggested an adoptive mother effect, with no hint of an interaction. PMID- 1417678 TI - Sex ratio and factors influencing family size in a human population from Spain. AB - Six hundred and eight students from the Faculty of Biological Sciences of Valencia (Spain) provided information about secondary sex ratio and family size of the parental, present, and projected generation. The average number of children was 3.59, 3.05, and 2.10 and the secondary sex ratio was 113.3, 101.2, and 98.6 for the parental, present, and projected generation respectively. Combination of sexes of the first two children had a significant effect in the parental and the present generations. There was no consistent association between sexes of successive and sexes of nonsuccessive children within families. The most preferred combination of sexes in the projected generation was one male-one female, and male-female was the most preferred permutation. Strong preferences for the firstborn to be male and for an alternation of sexes were also indicated. PMID- 1417679 TI - Developmental isolation and subsequent adult behavior of Drosophila paulistorum. I. Survey of the six semispecies. AB - We present results deriving from the inception of an investigation (involving 4,000 scored matings) into the development of discriminatory behavior in Drosophila paulistorum. We examined two complementary situations for their effects on mating behavior: physical isolation (seclusion) beginning at each of six developmental stages and exposure to heterosemispecifics during all preadult stages (mixed culturing). Preadult seclusion at certain stages decreased sexual isolation between three of four semispecific pairs. Seclusion effect, or lack thereof, varied with semispecies and with the stage at which seclusion was imposed: the earlier the stage at which seclusion was initiated, the more drastic the effect. In contrast, mixed culturing increased sexual isolation between the one pair of semispecies that was tested. PMID- 1417680 TI - Sources of behavioral deviation modeled by early color preferences in quail. I. Behavioral synergism and systemic instability. AB - Differences between population-typical norms of individual variability were studied in five genetic lines of Japanese quail (Coturnix coturnix japonica); two (BL and RL) were bidirectionally selected for early approach preference between blue and red stimuli, two (Hi and Lo) for high and low imprintabilities to the same stimuli, and the fifth (CL) was an unselected genetic control line. Selection resulted in reliably divergent extreme choice performances and imprintabilities and in progressively increasing choice variances in the BL x RL hybrids and the Hi imprintability line. Experimentation tested and rejected the hypotheses that correlated selection of synergistically acting but otherwise extraneous stimulus influences, social interaction effects, or phototactic and short-term learning effects may have been responsible for the observed large variance increases. An alternative interpretation is discussed, according to which directional selection relaxes the genetic buffering and the variance increases reflect the resulting developmental instability of the trait. PMID- 1417682 TI - Direct and correlated responses to bidirectional selection for dustbathing activity in Japanese quail (Coturnix coturnix japonica). AB - Bidirectional selection was conducted for dustbathing activity in male Japanese quail over 17 generations. The response to selection was slightly asymmetrical, due mainly to scale effects and a threshold imposing discontinuity on the visible expression of dustbathing in the low line. Correlated responses to selection were found for latency to dustbathe, duration, intensity, and incidence of nonbathers. In general, changes followed linear patterns over time in both lines with the exception of quadratic change in nonbathers in the high line. Under artificial environment, only minor natural selection pressure is assumed to act on the expression of dustbathing behavior. PMID- 1417683 TI - Animal phobias versus claustrophobias: exteroceptive versus interoceptive cues. AB - The overall purpose of this investigation was to examine heterogeneity among specific phobias. In particular, the goals were to compare features of fear responding between individuals fearful of claustrophobic situations and individuals fearful of spiders/snakes, and to compare their response to hyperventilation challenges. By so doing, specific predictions were tested in relation to a conceptual model of exteroceptive and interoceptive fear cues. Using a nonclinical sample, 19 subjects with spider/snake phobias, 18 nonphobics, and 9 subjects with claustrophobias were exposed on two separate occasions to a live tarantula or python, a small closet, and a hyperventilation challenge. Dependent measures included subjective anxiety, panic attacks, physical symptoms, cognitive symptoms (or, fear of symptoms) and heart rate. In addition, subjects completed a standardized self-report scale that measures fear of bodily symptoms of arousal. It was found that subjects with claustrophobia reported more physical symptoms and cognitive symptoms than did subjects with snake/spider phobias, in response to their fear-relevant stimulus. In addition, claustrophobic subjects were more fearful of hyperventilation challenges and reported more fear of bodily symptoms, than did snake/spider phobic subjects. Finally, subjects with claustrophobia were as fearful of hyperventilation as they were of their fear relevant stimulus. Theoretical and empirical implications of these findings are discussed. PMID- 1417681 TI - Sources of behavioral deviation modeled by early color preferences in quail. II. Diathetic genes and the leftover variance "V(e)". AB - The sources of deviation from population-typical norms of variability were studied in relation to early approach preferences between colors in newly hatched Japanese quail chicks (Coturnix coturnix japonica). Subjects were drawn from an unselected genetic control line, two genetic lines that were artificially selected for extreme blue and red preferences, their hybrids, and a large set of backcross and assortatively derived generations. Large progressive increases were observed with selection in the leftover (V(e)) component of F1 variance and consistent additional variance increases in F2 hybrids. Backcross generations exhibited greater than expected expression of the blue and red preference genes. Discussion differentiates between diathetic and normative influences in preference deviations and relates the increased Ve to relaxed normative canalization of preference development by directional selection. PMID- 1417684 TI - Agoraphobic avoidance and panic frequency as predictors of laboratory induced panic reactions. AB - This study examined the importance of agoraphobic avoidance and frequency of panic as predictors of psychological and physiological responses of panic sufferers to a laboratory based provocation procedure. Psychophysiologic comparisons were made between 22 panic disorder patients and 15 controls, at baseline and across three periods of carbon dioxide gas inhalations (1, 3, 5%; balance oxygen). Subjective measures of anxiety, frightening cognitions and body sensations were obtained across the phases. Physiological measures of minute ventilation, breathing rate, tidal volume, end tidal CO2 and heart rate were also obtained. Between group comparisons revealed significant differences between the groups on the subjective measures with no significant differences occurring on the physiological measures. Within group analyses revealed that pre-session questionnaire measures of agoraphobia avoidance and panic frequency predicted the degree of anxiety, frightening sensations and cognitions during baseline and 5% CO2 inhalation. The results indicated that both self-reported agoraphobic avoidance and panic frequency are strong clinical predictors of psychological reactions of panic sufferers during laboratory provocation. PMID- 1417685 TI - Individual differences in the perception of bodily sensations: the role of trait anxiety and coping style. AB - Thirty young women participated in an experiment in which heart rate, blood pressure, respiration rate, skin conductance level and palmar sweat index were monitored at rest and during the administration of mental arithmetic, mirror drawing and cold pressor tasks. The accuracy of perception of somatic states was estimated by calculating within-subject correlations between four bodily sensations (racing heart, high blood pressure, shortness of breath and sweaty hands) and corresponding physiological parameters, assessed on eight occasions during the experiment. The accuracy of heart rate perception was highest, with a mean correlation between actual heart rate and ratings of racing heart of 0.76 and 66% of participants showing significant within-subject effects. The mean accuracy was 0.55 for systolic blood pressure, 0.48 for respiration rate, 0.47 for skin conductance level, and 0.64 for palmar sweat index. Accurate perception across physiological parameters did not cluster within individuals, and was not dependent on the range either of physiological changes or sensation ratings. Trait anxiety was not significantly associated with accuracy of somatic perception. Subjects with high trait anxiety reported larger increases in shortness of breath during tasks than did low anxious subjects, but this was not reflected in objective physiological measures. Information-seeking coping style, indexed by the monitoring scale of the Miller Behavioral Style Scale, was related to the accuracy of perception of skin conductance level and heart rate. The use of within-subject correlational strategies for assessing individual differences in perception of bodily states is discussed. PMID- 1417686 TI - Reaction time to threat stimuli in panic disorder and social phobia. AB - Two studies assessed response time among clinically anxious subjects and normal controls when presented with threat, positive and neutral stimuli under perceptual (lexical decision) and semantic (category decision) task conditions. In Study 1, panic disorder subjects' (n = 14) performance was compared to that of matched normal controls (n = 14) while in Study 2 social phobic subjects (n = 24) were compared to matched normal controls (n = 24). Relative to matched normal controls, panic disorder subjects but not social phobics tended to show greater slowing in performance on the more cognitively complex (category) task. A second finding, consistent across both studies was that, compared to the normal control groups, both panic and social phobic groups showed significantly slowed responses to threat words in both the perceptual and semantic tasks. Such findings are directly counter to the predictions of a mood congruence hypothesis. This apparent contradiction is resolved by a review of the literature which indicates that mood-related facilitation effects are obtained only in tasks which tap awareness of threat information rather than speed of response. It is suggested that while anxiety may produce enhanced awareness of threat, it may inhibit responsiveness to it. The results of these studies are seen as consistent with ethological theories of inhibited motoric responses under certain threat conditions. Furthermore, the findings suggest that caution is indicated in interpreting slowed reaction time to threat stimuli in tasks such as the Stroop color naming task as purely the result of attentional processes. PMID- 1417687 TI - Attention and memory for threat in panic disorder. AB - Recently, information processing paradigms have been utilized to explore the role of attentional and memory processes in the maintenance of clinical anxiety disorders. The present study extended these data using a dual-task paradigm to assess attentional vigilance and a cued recognition task to evaluate short-term memory effects in Panic Disorder (PD). Twenty PD patients and 20 normal controls completed a computerized task wherein they read aloud one of a pair of rapidly presented words (primary task) while simultaneously attempting to detect a small probe that appeared adjacent to one of the words (secondary task). Eighty stimulus words were chosen to represent four categories: physical panic-related threat, social threat, positive-emotional, and neutral. Reaction time and accuracy in detecting the probe were assessed, as well as psychophysiological responding (heart rate, skin conductance, EMG). Following task completion, a cued recognition task was administered to examine short-term memory of task stimuli. Results indicated that PD patients exhibited slower reaction times relative to normal controls during presentation of physical panic-related threat and positive emotional stimuli. A similar trend emerged for social threat stimuli, although the PD and control samples responded similarly to neutral stimuli. No group differences were found on the cued recognition measure or psychophysiological responding during task performance. The data are discussed in terms of possible implications for cognitive models of PD. PMID- 1417688 TI - Obsessions and compulsions: dimensional structure, reliability, convergent and divergent validity of the Padua Inventory. AB - This study presents data on dimensional structure, reliability, convergent and divergent validity of the Padua Inventory (PI). In a sample (n = 430) of normal Dutch subjects. The dimensional structure and the strength of the factors were comparable to those found in the Italian sample. The reliability of the PI was found to be satisfactory. As hypothesized substantial correlations were found between the PI and related scales of the Maudsley Obsessive-Compulsive Inventory (MOCI) and between the PI and the subscales Sensitivity, Hostility and Depression of the revised version of the Symptom Checklist. Low correlations were found between the PI on the one side and the Eysenck Personality Questionnaire revised Extraversion, Psychoticism and Social Desirability scale on the other side. Finally, the mean score of the PI differs across the Italian, American and Dutch samples. This is of theoretical interest and deserves further study. PMID- 1417689 TI - Suppression of emotional and neutral material. AB - Previous studies have indicated that suppression of a thought results in an immediate increase of the frequency of this thought and/or in a rebound effect, i.e. in a heightened frequency of this thought later on. The present study (n = 53) examined the relationship between suppression and emotionality of the to-be suppressed material. More specifically, it was investigated whether suppression of an emotional story results in stronger immediate enhancement or thought rebounds than suppression of a neutral story. There was a clear initial enhancement effect in the group suppressing a neutral story: subjects who tried to suppress experienced more target thoughts than subjects who did not try to suppress. In the neutral-story conditions, no rebound effect occurred. In the groups exposed to an emotional story, there was neither evidence of initial enhancement nor of a rebound. As most obsessions are related to emotional themes, the present findings cast doubt on the claim that the rebound phenomenon represents a valid laboratory model for clinical obsessions. PMID- 1417690 TI - The role of hyperventilation in panic disorder: a response to Ley (1991) AB - Ley (Behaviour Research and Therapy, 29, 301-304, 1991) provided a reinterpretation of experimental findings on the efficacy of breathing retraining plus cognitive restructuring in reducing the symptomatology of patients with panic disorder with agoraphobia which were presented in a 1989 article in this journal. On the basis of his reinterpretation, they concluded that our findings supported the central role of hyperventilation in panic attacks. Ley's arguments are discussed and we conclude that his reinterpretation provides new arguments against a hyperventilation theory of panic. Furthermore, recent evidence from empirical studies does not support a central role for hyperventilation in panic attacks. PMID- 1417692 TI - The use of tannin from chestnut (Castanea vesca). AB - After mimosa and quebracho extracts, chestnut extract is the third most important vegetable tannin used for leather production. It is produced only in Europe on the northern side of the Mediterranean sea. The extract is prepared by hot water extraction of the bark and timber, followed by spray-drying of the solution. Analysis shows that there are insignificant variations in extract quality between batches, so the extract can be used with modern automated leather production systems. The extract contains approximately 75 percent active tanning substances. The primary component is castalagin, along with smaller amounts of vescalagin, castalin, and vescalin. A castalagin-based pharmaceutical product is currently in use for prevention and treatment of diarrhea in pigs and cattle that is caused by changes in diet. The beneficial effect is due to prevention of water losses through mucous membranes. The castalagin may also form chelates with iron, which influences the reabsorption of the metal in the animal digestive tract. PMID- 1417691 TI - Prediction of outcome from cognitive-behavioral treatment of irritable bowel syndrome. AB - The presence of a diagnosable Axis I psychiatric disorder predicted significantly (P less than 0.001) lower likelihood of significant improvement among 90 irritable bowel syndrome patients given cognitive and behavioral treatments to help the disorder. Other psychological tests, including the MMPI, BDI, STAI, as well as demographic variables, failed to yield significant prediction. PMID- 1417693 TI - Study on the composition and structure of commercial chestnut tanning agent. AB - Current research has focused on the composition of commercially used chestnut tannin extracts so as to provide a quantitative basis for studies of reactions, structure-property relationships, and applications of chestnut tannin extract. Two chestnut tannins, vescalagin and castalagin, have been isolated using chromatography on Sephadex LH-20 and cellulose. The structures of these compounds have been established by means of nuclear magnetic resonance and fast atom bombardment mass spectroscopy. Some other components have been found and analyzed by chromatography and spectroscopy, but their structures have not as yet been completely defined. These structural features, together with quantitative results for each component, provide a better understanding of the mode of action of complex commercial chestnut tannin extracts. PMID- 1417694 TI - Pharmacologically active tannins isolated from medicinal plants. AB - Starting with the isolation of a crystalline tannin (geraniin) of mild property from a popular herb medicine (Geranii herba), various polyphenolic compounds including those belonging to new classes of tannins (oligomeric hydrolyzable tannins, complex tannins, and other metabolites and condensates) have been isolated from various medicinal plants. Noticeable biological and pharmacological activities (inhibition of carcinogenesis, host-mediated antitumor activity, antiviral activity, and inhibition of active oxygen, such as inhibition of lipid peroxidation and lipoxygenase, xanthine oxidase, and monoamine oxidase) have been found for several of these polyphenolic compounds. PMID- 1417695 TI - Antinutritional effects of condensed and hydrolyzable tannins. AB - Despite major structural differences, hydrolyzable and condensed tannins often produce similar antinutritional effects. The most common effects are diminished weight gains and lowered efficiency of nutrient utilization. The major biochemical basis for these effects appears not to be inhibition of dietary protein digestion but rather a systemic inhibition of the metabolism of digested and absorbed nutrients, particularly protein. In the case of condensed tannins, this inhibition is probably not due to polymeric tannin molecules, which are not absorbed from the digestive tract, but to associated lower MW polyphenols, which are readily absorbed. PMID- 1417696 TI - Prosopis cineraria leaf tannins: their inhibitory effect upon ruminal cellulase and the recovery of inhibition by polyethylene glycol-4000. AB - The condensed tannins from the Prosopis cineraria leaves were purified and fractionated in two groups (Kav 0.018 and 0.74) on a column of Sephadex LH-20 (2.5 x 27 cm) using 70 percent aqueous acetone as the eluent. The Kav for catechin was 0.946. Upon acid hydrolysis, both the condensed tannin fractions yielded three pigments including cyanidin-chloride, which was separated by column chromatography using polyvinylpyrrolidone absorbent and was identified by paper chromatography (Rf Forestal 0.476) and absorption maxima (lambda max 535 nm) in 1 percent HCl in methanol. The condensed tannin fraction Kav 0.74 at 0.01 percent and 0.02 percent in incubations with butanol-acetone powder of rumen liquor, inhibited cellulase activity by 65.9 +/- 2.1 and 78.99 +/- 4.5 percent, respectively. Inclusion of 0.5 percent of polyethylene glycol -4000 in the incubation mixture, reduced the inhibition to 41 and 46 percent, respectively. PMID- 1417698 TI - Widespread tannin intake via stimulants and masticatories, especially guarana, kola nut, betel vine, and accessories. AB - Tannins are increasingly recognized as dietary carcinogens and as antinutrients interfering with the system's full use of protein. Nevertheless, certain tannin rich beverages, masticatories, and folk remedies, long utilized in African, Asiatic, Pacific, and Latin American countries, are now appearing in North American sundry shops and grocery stores. These include guarana (Paullinia cupana HBK.) from Brazil, kola nut (Cola nitida Schott & Endl. and C. acuminata Schott & Endl.) from West Africa, and betel nut (Areca catechu L.) from Malaya. The betel nut, or arecanut, has long been associated with oral and esophageal cancer because of its tannin content and the tannin contributed by the highly astringent cutch from Acacia catechu L. and Uncaria gambir Roxb. and the aromatic, astringent 'pan' (leaves of Piper betel L.) chewed with it. In addition to the constant recreational/social ingestion of these plant materials, they are much consumed as aphrodisiacs and medications. Guarana and kola nut enjoy great popularity in their native lands because they are also rich in caffeine, which serves as a stimulant. Research and popular education on the deleterious effects of excessive tannin intake could do much to reduce the heavy burden of early mortality and health care, especially in developing countries. PMID- 1417697 TI - Polyphenols from Bulgarian medicinal plants with anti-infectious activity. AB - Three Bulgarian medicinal plants--Geranium macrorrhizum L. and G. sanguineum L. (Geraniaceae), and Epilobium hirsutum L. (Onagraceae) were analyzed phytochemically. Different polyphenols like flavonoids and tannis have been found to be principal constituents of the plants. A series of water or alcohol extracts was obtained, and their anti-infectious activity was tested. A significant inhibitory effect of water-alcohol extract and of four fractions from the polyphenolic mixture of E. hirsutum on the reproduction of influenza viruses in vitro, in ovo, and in vivo was established. Four extracts from G. macrorrhizum and three extracts from G. sanguineum were studied for in vitro inhibition of the growth of some Gram-negative bacteria (Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa), Gram-positive bacterium (Staphylococcus aureus), and fungus (Candida albicans). Some geranium extracts caused a strong increase of the survival rate in an infection with K. pneumoniae in mice. Augmentation of the nonspecific host resistance in relation to the influence of the extracts on the classical complement activation pathway was also studied. PMID- 1417699 TI - Plants of the Olympic Coastal Forests: ancient knowledge of materials and medicines and future heritage. AB - The indigenous people of the west coast of Washington State's Olympic Peninsula have used a wide variety of forest plants for centuries to make materials and medicines. The late David Forlines shared at least eight generations of the knowledge of uses of these plants for materials and medicines with us in hopes that this information might be used 'to help science catch up with the old people.' Dyes, paints and adhesives were some of the materials made. The medicines were often administered as teas, but in some cases, fresh plant material was required. Some parallels were found to European and Chinese uses of similar species. Plants from the family Rosaceae had the greatest number of medicinal uses, but several other plant families known to contain polyphenols were also encountered. The role of polyphenols in the use of these plants is difficult to estimate because in many cases the plants have not been studied chemically. A preliminary screening indicated that many of the plants were rich in procyanidins and associated compounds. PMID- 1417700 TI - Antitumor-promoting activities of tannic acid, ellagic acid, and several gallic acid derivatives in mouse skin. AB - Naturally occurring plant phenols with antimutagenic and anticarcinogenic activities were tested for their abilities to inhibit the biochemical and biological effects of the potent tumor promoter 12-O-tetradecanoyl-phorbol-13 acetate (TPA) in mouse epidermis in vivo. When applied topically to mouse skin, tannic acid (TA), ellagic acid, and several gallic acid derivatives all inhibit TPA-induced ornithine decarboxylase activity, hydroperoxide production, and DNA synthesis, three biochemical markers of skin tumor promotion. Moreover, in the two-step initiation-promotion protocol, the same phenolic compounds also inhibit the incidence and yield of skin tumors promoted by TPA. TA is the most effective of these treatments. Since they are already known to inhibit tumor initiation, the plant phenols protecting against skin tumor promotion by TPA may be universal inhibitors of multistage carcinogenesis. TA and other polyphenols, therefore, might be valuable in cancer therapy and/or prevention. PMID- 1417701 TI - Cotton condensed tannin: a potent modulator of alveolar macrophage host-defense function. AB - Alveolar macrophages are the resident airway cells primarily responsible for the protection of the lungs against inhaled toxins and other biologically active material. A number of functional capabilities constitute their host-defense function. They can phagocytize and inactivate foreign material by production of reactive oxygen intermediates or the action of hydrolytic enzymes. In the absence of phagocytosis, macrophages can secrete reactive oxygen intermediates or enzymes that inactivate extracellular biologically active material. They also can secrete metabolites of arachidonic acid and other cytokines that contribute to the inflammatory response of the lungs. Macrophages also secrete a variety of peptide and lipid chemotactic factors that lead to the recruitment of other inflammatory cells into the airways. The condensed tannins, which constitute a significant percentage of the water soluble compounds present in respirable cotton mill dust, dramatically alter the host-defense function of alveolar macrophages in vitro. Tannin inhibits both phagocytosis and production of reactive oxidants in a dose dependent manner with EC50's of 16 micrograms/mL and 3 micrograms/mL, respectively. This inhibition dramatically decreases the ability of resident alveolar macrophages to clear and detoxify potentially harmful inhaled particles. However, at similar concentrations, tannin stimulates the dose-dependent secretion (EC50 = 15 micrograms/mL) of a low molecular weight lipid neutrophil chemotactic factor that could result in an inflammatory reaction with the recruitment of neutrophils into the lungs. At slightly higher concentrations, tannin promotes the dose-dependent release of arachidonic acid from the macrophage membranes (EC50 = 65 micrograms/mL), which could also contribute to the local inflammatory reaction. Finally, tannin also causes secretion of the cytokine, interleukin-1, from the monocyte precursors of macrophages with an EC50 of 32 micrograms/mL. Interleukin-1 has been implicated as one of the causative agents in the development of fever. PMID- 1417702 TI - Condensed tannins in some forage legumes: their role in the prevention of ruminant pasture bloat. AB - For the past 20 years, the focus in our laboratory has been on finding the causes of ruminant pasture bloat and eventually breeding a bloat-safe alfalfa (Medicago sativa L.); i.e., with bloat potential reduced to the economic threshold. In the mid-seventies, the mechanisms of bloat were explored and found to be more physical than chemical. Characteristic of all bloating legumes after ingestion was a very rapid initial rate of ingestion by rumen microbes. Through the study of bloating and non-bloating legumes, factors were elucidated in the plant that would slow this process. One of these factors was the presence of condensed tannins in the herbage. Some of the non-bloating legumes contained these secondary metabolites, but no condensed tannins were found in any of the bloating legumes. Therefore, species containing an appreciable amount of condensed tannins in their leaves and stems are considered to be non-bloating. Conventional breeding methods have not been successful in producing an alfalfa with condensed tannins in its herbage. New approaches using tissue culture techniques are being attempted, but genetic engineering has the greatest potential for success. PMID- 1417704 TI - Decreased susceptibility to arrhythmias in hypertrophied hearts of physically trained rats. AB - The aim of this study was to investigate the propensity to develop cardiac arrhythmias during an acute period of ischemia between normal and hypertrophied (by means of a swimming training regimen) rat hearts. We used the coronary artery ligation in vivo technique which induced the occurrence of cardiac arrhythmias in rats that was followed by the determination of the occluded zone size. This study was coupled to an in vitro study using a two-compartment tissue bath in which half of the ventricular preparation was exposed to normal conditions and the other to ischemic conditions (low pH, hypoxia, and hyperkalemia). We also measured the collagen content and the DNA/protein ratio of the hearts. Twenty eight male Wistar rats submitted to an eight-week swimming training (SWT) and twenty-eight cage-confined matched rats were used for the studies. SWT resulted in a 14% decrease in mean body weight and an 8% increase in absolute heart weight. We also observed a resting bradycardia in the trained animals and blood pressure remained unchanged between the two groups. Collagen content was unchanged and DNA/protein ratio was lower in the left ventricle of trained animals. During a 30-min period of coronary artery ligation, SWT rats demonstrated fewer ischemia-induced arrhythmias as compared to controls. The size of the zone affected by the vasal occlusion was lower in trained animals. Electrophysiological data recorded in the two-compartment bath showed a marked prolongation of action potential duration and refractory period in the SWT rat hearts. During the 15-min period of in vitro ischemia there was a global alteration of all electrophysiological parameters which did not differ between the two groups. Our data support the hypothesis that resting bradycardia and decrease in ischemic zone size may be involved in the arrhythmogenic protection observed in hypertrophied hearts of swimming rats after an acute ligation of the left coronary artery. Our results also indicate that cardiac hypertrophy, as defined by quantitative changes in cardiac mass or by the electrophysiological alterations that are related to its development, is not necessarily associated with an increased risk for the occurrence of arrhythmias. PMID- 1417703 TI - Effects of triiodothyronine in spontaneously hypertensive rats. Studies on cardiac metabolism, function, and heart weight. AB - We have studied the effects of triiodothyronine (T3) on heart function, on the myocardial oxidative pentose phosphate pathway, and on heart weight in spontaneously hypertensive (SHR) rats. Another aim was to examine whether these T3-effects may be reversible. T3 was administered daily (0.2 mg/kg s.c.) for 14 days. Compared to the untreated SHR controls, T3 induced an increase in heart rate (beats/min) from 357 +/- 10 (n = 17) to 553 +/- 10 (n = 17), in the pressure rate-product (mm Hg/min) from 78 400 +/- 4500 (n = 15) to 113 700 +/- 4800 (n = 15), and in the heart weight/body weight ratio (mg/g) from 4.2 +/- 0.2 (n = 20) to 5.8 +/- 0.2 (n = 19). The activity of myocardial glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (units/g protein), was elevated from 4.2 +/- 0.2 (n = 9) to 7.0 +/- 0.6 (n = 9) after 14 days of T3-treatment, while the activity of 6 phosphogluconate dehydrogenase, one of the following enzymes in the pathway, was not altered appreciably. These changes returned to the respective control values when T3-treatment was discontinued for 14 days. Our results demonstrate that T3 had a positive chronotropic effect and induced an additional heart enlargement in an animal model with already established cardiac hyperfunction and hypertrophy. The effects on heart function and weight, which were fully reversible, were not as pronounced as in normal Sprague-Dawley rats. PMID- 1417705 TI - The effect of magnesium added to secondary cardioplegia on postischemic myocardial metabolism and contractile function--a 31P NMR spectroscopy and functional study in the isolated pig heart. AB - This study investigated whether increasing the magnesium concentration during secondary cardioplegia improves postischemic myocardial recovery. Twenty-four isolated pig hearts were divided into four groups. All hearts were initially subjected to control perfusion with modified Krebs-Henseleit solution for 30 min, followed by a single infusion of St. Thomas' solution #2. The hearts were then maintained without perfusion at 12 degrees C for 4 h. Following this hypothermic preservation, the hearts in group I were reperfused with modified Krebs-Henseleit solution for 50 min, while hearts in group II and III were reperfused with a secondary cardioplegic solution containing 16 or 0 mmol/L magnesium, respectively, for 20 min followed by 30 min of perfusion with modified Krebs Henseleit solution. In group IV, the hearts were initially reperfused with Krebs Henseleit solution containing 16 mmol/L potassium for 20 min, followed by 30 min of reperfusion with modified Krebs-Henseleit solution. The changes in high-energy phosphates and intracellular pH were monitored throughout the experiments using 31P nuclear magnetic resonance (NMR) spectroscopy. Heart rate, left-ventricular systolic developed pressure, and rates of pressure increase and decrease were measured during control perfusion and reperfusion to calculate the percent contractile functional recovery. Needle biopsies for measurement of energy metabolites with high performance liquid chromatography were performed at the end of preservation and reperfusion to confirm the NMR measurements. All six hearts in group I showed significantly less recovery of contractile function during reperfusion when compared to the hearts in groups II, III, IV (p less than 0.05). There was no difference in either recovery of metabolism or mechanical function among the latter three groups of hearts. None of hearts in groups II, III, and IV showed ventricular fibrillation, which occurred in all six hearts of group I upon reperfusion. The results suggest that a short period of re-arrest perfusion following ischemia ("secondary cardioplegia") improves postischemic contractile functional recovery and prevents reperfusion-induced ventricular fibrillation. Increased magnesium concentration in the secondary cardioplegia did not provide additional benefit to the ischemic myocardium, possibly due to the low permeability of the sarcolemmal membrane to magnesium. PMID- 1417706 TI - Reperfusion-induced arrhythmias and myocardial ion shifts: a pharmacologic interaction between pinacidil and cicletanine in isolated rat hearts. AB - Pinacidil is a member of the new antihypertensive drug family possessing an action that involves an increased potassium efflux in vascular and cardiac muscle. We investigated the contribution of opening of ATP-sensitive potassium channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na+, K+, Ca2+, and Mg2+ in isolated rat hearts. After 30 min of normothermic global ischemia, pinacidil with 1 to 60 mumol/l failed to reduce the incidence of reperfusion-induced arrhythmias, even on the postischemic/reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (the duration of ischemia was reduced to 25 min), pinacidil treatment was associated with a greater incidence of reperfusion induced arrhythmias (100%) as compared to the control value (50%). These proarrhythmic effects of pinacidil were also reflected in a maldistribution of myocardial ion contents both in nonischemic and ischemic/reperfused hearts. Cicletanine, a furopyridine antihypertensive agent that has no effect on coronary resistance, reduced the incidence of reperfusion arrhythmias, and its antiarrhythmic effect was antagonized by pinacidil. The same observation was made in relation to myocardial ion content, e.g., pinacidil-induced K+ loss and Ca2+ gain were antagonized by cicletanine, both in nonischemic and ischemic/reperfused hearts. It is hypothesized that the increased tendency to develop reperfusion induced ventricular fibrillation is associated with the pinacidil-induced K+ efflux. The present study does not attempt to address the question of specific ionic currents; however, it has been suggested that proarrhythmic and antiarrhythmic effects of pinacidil and cicletanine, respectively, may relate to same receptor sites in which the latter may reflect a specific blockade of the outward K+ ion current via ATP-sensitive K+ channels. If this is so, the use of K+ channel openers as antihypertensive agents may be of particular concern in that population of postinfarction patients who are known to be at high risk of sudden coronary death. PMID- 1417707 TI - Ibuprofen abolishes the increase in leucocyte chemiluminescence observed during ischemic myocardial failure, but fails to improve hemodynamic function. AB - The aim of the study was to evaluate 1) whether the ability of leucocytes to produce oxygen radicals was increased by ischemia and 2) if ibuprofen pretreatment could influence leucocyte oxygen radical production, hemodynamic function, and myocardial oxygen consumption during acute ischemic myocardial failure. We studied two groups of anesthetized dogs (control and ibuprofen treated), both subjected to coronary embolization with polystyrene microspheres (diameter 50 microns). The embolization procedure was ended when left-ventricular end-diastolic pressure in both groups exceeded 20 mm Hg. Before and after induction of ischemia leucocytes were isolated and stimulated with opsonized zymosan, and oxygen radical production was measured using the luminol-dependent chemiluminescence technique. Significant increase occurred in oxygen radical production (from 10.9 +/- 2.2 to 16.3 +/- 2.3 x 10(5) counts x 10(6) cells-1 x 60 min-1) 90 min after failure in the control group, whereas in ibuprofen-pretreated dogs oxygen radical production was unchanged. Hemodynamic registrations and myocardial oxygen consumption 90 min after failure were, however, not significantly different in control dogs and dogs pretreated with ibuprofen. Thus, in the present study, within the first 90 min of acute ischemic failure, a decrease in the ability of leucocytes to produce oxygen radicals was not related to significant changes in myocardial function. PMID- 1417708 TI - Exposure of rats to low concentration of cigarette smoke increases myocardial sensitivity to ischaemia/reperfusion. AB - It is suggested that passive smoking or smoke-exposure increase the risk of coronary heart disease. The same mechanisms as active smoking might play a role. The aim of this study was to determine whether exposure to smoke aggravated ischaemia/reperfusion injury. As a parameter of cellular function and integrity mitochondrial oxidative function was measured. Low molecular weight iron (LMWI) and alpha-tocopherol levels were determined to assess the possibility of toxic hydroxyl radical involvement in myocardial ischaemia/reperfusion injury of smoke exposed rats. Rats were exposed to a small concentration of cigarette smoke for 2 months (the carboxyhemoglobin concentration did not increase), whereafter hearts were isolated and subjected to ischaemia and ischaemia followed by reperfusion. Mitochondrial oxidative function, low molecular weight iron and alpha-tocopherol were determined. The impairment in mitochondrial oxidative function, LMWI content elevation and the decrease in alpha-tocopherol concentration during ischaemia/reperfusion were significantly more severe in hearts of smoke-exposed rats than non-smokers. These results suggest that exposure to smoke increased the sensitivity of hearts to ischaemia/reperfusion injury, and that a free radical mechanism might participate. PMID- 1417710 TI - Measuring children's social skills using microcomputer-based videodisc assessment. AB - This article describes the development of a microcomputer-based videodisc assessment prototype for measuring children's social skills. The theoretical and empirical foundations for the content are described, and the contributions of interactive microcomputer-based video technology to assessment of children with handicaps are detailed. An application of Goldfried and D'Zurilla's "behavior analytic" approach to development of the content of assessments is presented, and the related video and computer technology development is detailed. The article describes the conceptual foundations of the psychometrics of the assessment prototype as well as the psychometric methodology that was employed throughout the development process. Finally, a discussion of the potential applications and implications of the social skills assessment prototype is included. PMID- 1417709 TI - Colored microspheres reveal interarterial microvascular anastomoses in canine myocardium. AB - While the presence of microvascular intercommunication within an individual myocardial arterial bed is well documented, there is a paucity of data to support the existence of anastomoses emanating from independent arterial beds. Simultaneous in-vivo infusion of two different colored microsphere suspensions into the left anterior descending (LAD) and left circumflex (LCx) coronary arteries identified a specific interface region of canine myocardium that was perfused by both arterial branches. Subsequent microscopic/morphometric analysis of 40 microns serial sections in eight hearts revealed clustering of microspheres in their respective perfusion territories (red microspheres in the LAD region away from the interface, blue microspheres in the LCx field away from the interface), along with a mutually perfused borderzone. In each tissue section, two regions within this zone were identified and their maximum widths measured. One region was defined as the Interface Transition Zone (ITZ) (mean width = 5251 +/- 770 microns; mean +/- SD). This region was formed by an intermingling of microvessels supplied by the parent arteries of the adjacent perfusion territories; it separated tissue containing only one or the other colored microspheres. The second region was defined as the Boundary Watershed Zone (BWZ) (mean zone width = 3151 +/- 611 microns; mean +/- SD). This region was formed by capillaries containing sphere aggregates of both colors; it was located exclusively within the ITZ. In addition, the ITZ and BWZ were significantly wider in subepicardial than in subendocardial regions (p less than 0.001). PMID- 1417711 TI - A comparison of the verbal social behavior of adolescents with behavioral disorders and regular class peers. AB - Improved social functioning of adolescents with behavioral disorders (BD) is of critical importance for the successful integration of these students in school, domestic, vocational, and community settings. Three comparisons were addressed in the study; overall verbal responding of BD adolescents was compared to verbal responding of their regular class peers, verbal responding of the same BD adolescents was compared across their self-contained and mainstreamed settings, and responding of the BD adolescents when in mainstreamed settings was compared to responding of regular class peers. Portable microcomputers were used to collect data across 10 categories of verbal responding for 14 BD adolescents and 14 regular class peers. Results supported several general conclusions: (a) Adolescents with behavioral disorders engaged in more negative verbal responding than their regular class peers; (b) BD adolescents exhibited less inappropriate verbal behavior when in the mainstream than when self-contained; and (c) when in the mainstream, the verbal behavior of BD students was similar to that of their regular class peers. Implications of the general and specific differences that emerged from the comparisons were presented and discussed. PMID- 1417712 TI - The overtures of preschool social skill intervention agents. Differential rates, forms, and functions. AB - The purpose of this study was to examine the differential topographies and functions of social behaviors directed by normally developing preschoolers to their playmates with autism. Social interaction data from intervention phases of a study by Kohler, Strain, Hoyson, DeCesare, Donina, and Rapp were analyzed in three different ways. First, the frequency of four behaviors commonly included in social interaction training or assessment procedures (i.e., play organizer suggestions, share offers or requests, assistance offers or requests, and general statements) was examined. Second, the effects of each peer behavior on the immediate response of 3 children with autism were examined. Finally, the impact of each behavior that led to a positive response on the duration of subsequent target child-peer social interactions was examined. The four social behaviors had differential topographical and functional properties. Shares and play organizers occurred most frequently and generated the highest proportion of positive responses from all 3 children with autism. Conversely, assistance offers or requests occurred less often and received a lower percentage of positive responses. However, assistance behaviors consistently led to the longest social interactions. Implications of these results for future social skills training and research are discussed. PMID- 1417713 TI - Recognition of facial expressions of emotion by persons with mental retardation. A matched comparison study. AB - Children and adults with mental retardation were tested on their ability to recognize facial expressions of emotion. The sample consisted of 80 children and adults with mental retardation and a control group of 80 nonhandicapped children matched on mental age and gender. Ekman and Friesen's normed photographs of the six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) were used in a recognition task of facial expressions. Subjects were individually read two-sentence stories identifying a specific emotion, presented with a randomized array of the six photographs of the basic facial expressions of emotion, and then asked to select the photograph that depicted the emotion identified in the story. This procedure was repeated with 24 different stories, with each of the six basic emotions being represented four times. Results showed that, as a group, individuals with mental retardation were not as proficient as their mental-age matched nonhandicapped control subjects at recognizing facial expressions of emotion. Although adults with mild mental retardation were more proficient at this task than those with moderate mental retardation, this finding was not true for children. There was a modest difference between the children with moderate mental retardation and their nonhandicapped matched controls in their ability to recognize facial expression of disgust. PMID- 1417714 TI - Enhancing the ability of adults with mental retardation to recognize facial expressions of emotion. AB - The ability to recognize accurately and respond appropriately to facial expressions of emotion is essential for interpersonal interaction. Individuals with mental retardation typically are deficient in these skills. The ability of 7 adults, 1 with severe and 6 with moderate mental retardation, to recognize facial expressions of emotion correctly was assessed. Then, they were taught this skill using a combination of a discrimination training procedure for differentiating facial movements, directed rehearsal, and Ekman and Friesen's "flashing photograph" technique. Their average increase in accuracy over baseline was at least 30% during the course of the training and over 50% during the last 5 days of the training phase. Further, these individuals were able to generalize their skills from posed photographs to videotaped role plays and were able to maintain their enhanced skills during the 8 to 9 months following the termination of training. This is the first study to show that individuals with mental retardation can be taught skills that enhance their ability to recognize facial expressions of emotion. PMID- 1417715 TI - Pathways to maladaptive parenting with mothers and their conduct disordered children. AB - Maladaptive parenting with conduct disordered children appears to involve two social interaction traps called compliance and inconsistency. A mother's participation in these traps is thought to be influenced by her child, by the quality of the mother's life, and by her perceptions of child behavior. This study was an attempt to assess these influences and to examine their correlations with maternal trap participation. To do so, 33 clinic-referred conduct disordered children and their mothers were evaluated through direct observation, maternal self-reports, and maternal observations of home videotapes depicting mother and child. The data were then analyzed as correlational paths among trap measures and measures of the suspected influences. Results showed the two traps to be distinctly different processes, and inconsistency appeared to represent a more complex process than did compliance. Discussion of the findings centered on problems in maternal care of conduct disordered children and prospects for clinical interventions with these mother-child dyads. PMID- 1417716 TI - Generalization in social behavior research with children and youth who have emotional or behavioral disorders. AB - This article presents a critical analysis of social behavior research with students who have emotional or behavioral disorders (EBD). In particular, it focuses on issues of generalized responding and a technology of generalization promotion. From a review of selected studies the conclusion is drawn that (a) researchers too rarely examine generalization in social behavior research, (b) studies that provide analysis of generalization rely on the least analytic approaches, and (c) generalization is seldom presented as a dependent variable of central interest in social behavior research with EBD students. Guidelines for further research in the area of generalization promotion are offered. PMID- 1417717 TI - [Light and electron microscopic studies of calf kidneys after exposure to subtoxic lead levels]. AB - Eight calves were fed from the fourth to the twentieth week of age a milk powder diet containing 40 mg lead acetate per kg dry substance. This is twice the lead concentration legally permitted. In average, each animal has daily taken up 0.834 mg lead per kg body weight. Eight calves were used as controls. The animals gained the usual fattening weights and did not show clinical symptoms. Beginning with week 14, increased levels of blood urea were encountered in the animals which received lead in their diet. Morphologically, severe renal lesions were found in these calves. The kidneys were increased in weight, pale and of firm consistency. Histologically, fibrosis and periglomerular interstitial non purulent nephritis were found. Light- and electronmicroscopically, numerous intranuclear inclusion-bodies typical for lead poisoning were demonstrated in epithelial cells of proximal tubules. The results show, that daily uptake of less than 1 mg lead per kg body weight must be considered as a toxic dose for calves, and not 5-7 mg as stated in literature. PMID- 1417718 TI - [Morphometric studies of the proximal tubules of the rat kidney considering the effect of the method of killing]. AB - 120 male rats belonging to two different strains (Han: WIST, Han: SPRD) and two different weight groups (group I: lighter body weight, group II heavier body weight) were killed on three different methods (decapitation, Nembutal -overdose greater than 250 mg/kg b.w. i.p. less than, exsanguination in Nembutal anaesthesia greater than 100 mg/kg b.w. i.p.). Subsequently, changes in tubuli contorti I of the left kidneys were examined morphometrically. The mean total area, luminal area and epithelial area were evaluated as well as the mean diameter of the tubular nuclei. Concerning the areas of the proximal tubules only the luminal areas show differences between the Wistar and the Sprague-Dawley strain. The total, luminal and epithelial area in the rats belonging to the weight group II were significantly larger than in the rats belonging to weight group I. With one exception this could be noticed within both strains and all three modes of killing. In both strains and weight groups the rats were killed by Nembutal -overdose or exsanguination showed significantly smaller total, luminal and epithelial areas than the rats that were decapitated. Possible cause heretofore are discussed. Differences between the tubular areas of the rats that were killed by Nembutal -overdose and those that were killed by exsanguination after Nembutal -anaesthesia could not be established. The measurements of nuclei diameters in the proximal tubules did not lead to clearly different results between both strains, weight groups and the various modes of killing. PMID- 1417719 TI - [Old age--a disease?]. AB - The process of aging is discussed in relation to the environment of an individual and the evolution. Aging occurs hierarchically at a molecular, cellular, and systemic level. These physiologic processes of aging are accompanied by diseases, age-dependent and age-related diseases can be differentiated. PMID- 1417720 TI - Peroxidase-antiperoxidase labelling of Leishmania amastigotes in formalin fixed and paraffin embedded tissue sections. AB - A modified PAP-Method (peroxidase-antiperoxidase) is established for laboratory use to demonstrate Leishmania spp. amastigotes in paraffin sections of experimentally and naturally infected dogs. The results demonstrate that the PAP technique is a valuable tool to detect Leishmania amastigotes in tissue sections with low parasite density. PMID- 1417721 TI - [Formal pathogenesis, average age and breed distribution in the comparison of 61 Lysodren-treated and 36 untreated cases of canine hyperadrenocorticism which were dissected in the years 1975 to 1991 at the Institute for Veterinary Pathology of the Free University of Berlin]. AB - 61 Lysodren -treated dogs with hyperadrenocorticism are compared with 36 untreated dogs with the same disease. 75.14% of the treated dogs had pituitary dependent-hyperadrenocorticism (PDH) whereas this diagnosis was found in 63.89% of the untreated dogs. A functioning adrenocortical tumor (FAT) was found in 13.11% of the treated dogs but was evident in 22.22% of the untreated dogs. Simultaneous pituitary and adrenal Cushing's syndrome (PDH/FAT) were found in 11.48% of the treated and 8.33% of the untreated cases. Sex distribution was equal in both groups. Overall slightly more females than males were affected by the disease. Poodles (38.14%) and dachshunds (23.71%) were the mainly affected races. Race-distribution of diseased animals is compared to the overall race distribution in a ten years statistic (1981-1990) of all necropsied animals (Walter und Schwegler, 1992). The mean age of Lysodren -treated dogs with a PDH diagnosis (10.0 years) is lower as the mean age of untreated dogs with the same diagnosis (10.3 years). Reasons for this unexpected finding are discussed. PMID- 1417722 TI - [Globular periodontal cement dysplasia in a black rhinoceros (Diceros bicornis)]. AB - A globular periodontal cementous dysplasia in a 18 years old black rhinoceros (Diceros bicornis) is diagnosed by gross pathology, X-ray, and by histological examinations. The findings are discussed. PMID- 1417724 TI - A mammalian epididymal protein with remarkable sequence similarity to snake venom haemorrhagic peptides. AB - Following spermatogenesis in the testis, mammalian spermatozoa pass into the epididymis, where they undergo changes which confer on them forward motility and the ability to recognize and penetrate the egg. Many of these maturation events involve androgen-regulated epididymal proteins which become associated with the sperm membrane, and/or effect changes to integral sperm membrane proteins. Here we report the sequence of an 89 kDa androgen-regulated protein from rat (Rattus norvegicus) and monkey (Macaca fascicularis) epididymis that is synthesized exclusively in the caput region and is localized on the apical surface of its principal epithelial cells. This protein shows remarkable similarity to a variety of proteases and disintegrins found in snake venoms and is similar to, but distinct from, the guinea-pig sperm surface PH-30 alpha/beta complex recently implicated in sperm-egg recognition and fusion. PMID- 1417725 TI - Production, processing and partial purification of functional G protein beta gamma subunits in baculovirus-infected insect cells. AB - As a result of the inability to resolve the heterogeneous mixture of G protein beta gamma subunits present in tissues, it has not been possible to compare different beta gamma subunits of the G proteins in terms of their proposed roles in receptor-effector coupling. This study was undertaken to establish the utility of the baculovirus expression system in producing homogeneous beta gamma subunits of defined composition for the comparative analysis of these subunits in reconstitution systems. In this study we report the expression, and appropriate post-translational processing, of recombinant beta 2, gamma 2 and gamma 3 subunits. In addition, we show that the recombinant beta gamma subunits can be readily purified, and can functionally interact with the alpha subunits of the G proteins. PMID- 1417726 TI - Okadaic acid produces changes in phosphorylation and translocation of proteins and in intracellular calcium in human neutrophils. Relationship with the activation of the NADPH oxidase by different stimuli. AB - Okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, profoundly influenced the activity of the NADPH oxidase of human neutrophils. It strongly inhibited stimulation of superoxide generation by phorbol 12-myristate 13-acetate (PMA) and impaired translocation of protein kinase activity and of the two cytosolic components p47-phox and p67-phox to the plasma membrane. The increase in the phosphorylation of the cytochrome b-245 subunits p22-phox and gp91-phox after stimulation was also blocked. Inhibition of activity was associated with a decrease in cytosolic free Ca2+ and was reversed by the Ca2+ ionophore A23187, which also restored protein translocation and phosphorylation of the cytochrome. This effect of A23187 was itself blocked by preincubation with cyclosporin A, suggesting that calcineurin might be involved in the re-activation process. In contrast with PMA, the response to the bacterial peptide fMet-Leu-Phe was greatly prolonged after an initial decrease in the rate of onset of NADPH oxidase activity. PMID- 1417723 TI - Import of proteins into peroxisomes and other microbodies. PMID- 1417728 TI - Evidence that adhesion of electrically permeabilized platelets to collagen is mediated by guanine nucleotide regulatory proteins. AB - Adhesion of electrically permeabilized platelets to collagen was found to be essentially independent of free Ca2+ concentration in the medium. Addition of stable GTP analogues increased the proportion of adhering cells about 5-fold. This effect was inhibited by guanosine 5'-[beta-thio]diphosphate, cytochalasin D or monoclonal antibodies to glycoprotein Ia. In contrast, the protein kinase C inhibitor staurosporine had only a small effect on the GTP-analogue-enhanced adhesion of the permeabilized cells to collagen. These results suggest that a guanine nucleotide regulatory (G)-protein is directly linked to the collagen receptor and is involved in the actin-dependent recruitment of additional collagen receptors. PMID- 1417727 TI - Comparison of diglyceride production from choline-containing phosphoglycerides in human neutrophils stimulated with N-formylmethionyl-leucylphenylalanine, ionophore A23187 or phorbol 12-myristate 13-acetate. AB - The turnover of choline-containing phosphoglycerides (PC) in response to agonist stimulation is well documented in human neutrophils. We have now compared the enzymic pathways of N-formylmethionyl-leucylphenylalanine (fMLP)-, A23187- and phorbol-12-myristate 13-acetate (PMA)-induced diglyceride (DG) and phosphatidic acid (PA) generation in these cells. In order to distinguish between phospholipase C- and D-mediated PC breakdown, human neutrophils were radiolabelled with 1-O-[3H]alkyl-2-acyl-glycero-3-phosphocholine and stimulated in the presence of ethanol or propranolol. The addition of 0.5% ethanol to the incubation mixture resulted in the production of phosphatidylethanol, indicative of phospholipase D activation, in response to all three stimuli. Concomitant with phosphatidylethanol formation was a partial block of PA production. The production of DG was also partially blocked by addition of ethanol. Propranolol (200 microM) was also used to assess the contributions of phospholipases C and D toward DG generation. Inhibition of PA phosphohydrolase by propranolol resulted in the complete abolition of DG generation when neutrophils were stimulated with fMLP. In contrast, propranolol only partially inhibited DG generation in response to A23187 and PMA. These results suggested that DG production in response to fMLP stimulation is mediated via the activation of phospholipase D, whereas A23187- or PMA-induced DG generation may involve more than one pathway. However, examination of the water-soluble choline metabolites produced indicated that phospholipase D was responsible for the production of PA and DG in response to all three stimuli. PMID- 1417729 TI - Immunoreactive folate-binding proteins from human saliva. Isolation and comparison of two distinct species. AB - Human saliva contains a single 72,000-M(r) species which specifically reacted with rabbit anti-[human placental folate receptor (PFR)] serum on SDS/PAGE and Western blots. Although a specific radioimmunoassay for human PFR and related folate-binding proteins (FBPs) identified 55 ng of cross-reacting material (CRM) per mg of crude salivary proteins, only a minor fraction (1.6 ng) specifically bound radiolabelled folate. The major fraction of CRM did not contain bound endogenous folate and did not bind radiolabelled folates. On the basis of folate binding, salivary CRM species to PFR were designated as either functional (f-FBP) or non-functional (nf-FBP) species respectively. nf-FBPs and f-FBPs were isolated by different purification schemes. Both purified f-FBPs and nf-FBPs migrated as a single apparent 72,000-M(r) species on SDS/PAGE, but on Sephacryl S-200 gel filtration and sucrose-density-gradient ultracentrifugation they were eluted/sedimented with 40,000-M(r) markers. Each microgram of purified f-FBP and nf-FBP was measured in the radioimmunoassay for PFR as being equivalent to 18 ng and 24 ng of CRM respectively, indicating low epitope-relatedness to PFR. The Kd of f-FBPs was 50 pM and 0.94 mol of folate was bound/mol of protein. f-FBPs exhibited an unusual dependence on Triton X-100 for optimal ligand binding, despite the fact that Triton X-100 micelle binding was not demonstrated. The relative order of affinity of f-FBPs for pteroylglutamate greater than methotrexate greater than 5-formyltetrahydrofolate greater than 5 methyltetrahydrofolate was also distinct from that of purified PFR. Whereas amino acid and carbohydrate analysis revealed that nf-FBP (M(r) 51,400) and f-FBP (M(r) 39,200) were distinct glycoproteins with 8 and 13% carbohydrate respectively, isoelectric focusing and immunological studies suggested some structural identity. The presence of f-FBP and nf-FBP in normal saliva raises new questions about their possible role in vivo. PMID- 1417731 TI - Binding energy and catalysis. Fluorinated and deoxygenated glycosides as mechanistic probes of Escherichia coli (lacZ) beta-galactosidase. AB - Kinetic parameters for the hydrolysis of a series of deoxy and deoxyfluoro analogues of 2',4'-dinitrophenyl beta-D-galactopyranoside by Escherichia coli (lacZ) beta-galactosidase have been determined and rates found to be two to nine orders of magnitude lower than that for the parent compound. These large rate reductions result primarily from the loss of transition-state binding interactions due to the replacement of sugar hydroxy groups, and such interactions are estimated to contribute at least 16.7 kJ (4 kcal).mol-1 to binding at the 3, 4 and 6 positions and more than 33.5 kJ (8 kcal).mol-1 at the 2 position. The existence of a linear free-energy relationship between log(kcat./Km) for these compounds and the logarithm of the first-order rate constant for their spontaneous hydrolysis demonstrates that electronic effects are also important and provides direct evidence for oxocarbonium ion character in the enzymic transition state. A covalent intermediate which turns over only extremely slowly (t1/2 = 45 h) accumulates during hydrolysis of the 2 deoxyfluorogalactoside, and kinetic parameters for its formation have been determined. This intermediate is nonetheless catalytically competent, since it re activates much more rapidly in the presence of the transglycosylation acceptors methanol or glucose, thereby providing support for the notion of a covalent intermediate during hydrolysis of the parent substrates. PMID- 1417730 TI - Inhibition by heparin of Fe(II)-catalysed free-radical peroxidation of linolenic acid. AB - Heparin, in a concentration-dependent manner, inhibited the generation of conjugated dienes and thiobarbituric acid-positive substances when incubated with Fe2+ and gamma-linolenic acid. In the conjugated diene assay, other glycosaminoglycans, on a molar basis calculated with respect to their respective hydrated disaccharide repeat units, were less effective than heparin. Heparin which had been re-N-sulphonated after removal of both N-sulphonates and O sulphates, and heparin in which iduronate residues had been reduced to idose residues, were largely unaffected in their activity. Removal of both N sulphonates and O-sulphates greatly reduced the effectiveness of the heparin. Analysis of the effects of heparin fragments generated by heparinase I treatment of heparin showed that depolymerization decreased the effectiveness of the heparin. It is possible that heparins and related strongly acidic polysaccharides may function as endogenous antioxidants, and that sequestration by them, or harmless oxidation by them, of ions such as Fe2+, contributes to their effectiveness. PMID- 1417732 TI - Binding characteristics of Mn2+, Co2+ and Mg2+ ions with several D-xylose isomerases. AB - D-Xylose isomerases are metal-ion (Mn2+, Co2+, Mg2+)-requiring tetrameric enzymes. Both the stoichiometry and the binding constants have been determined by titrating the metal-ion-free enzymes from five organisms (Actinomycetaceae and more divergent bacteria) with the respective metal ions using the enzyme activity as indicator of active complex-formation. The following characteristics have been observed for each specific isomerase: (i) two essential metal ion sites (one structural and one catalytic) exist per subunit; (ii) the metal ion binding at one site does not affect the binding at the other site; (iii) of the four possible configurations E, aE, Eb and aEb, only the double-occupied enzyme is active; (iv) the metal ion activation is a time-dependent process; (v) the dissociation constants for both the structural and catalytic sites may be identical or may differ by one or higher orders of magnitude; (vi) metal ion binding is stronger in the order Mn2+ greater than Co2+ much greater than Mg2+; (vii) pronounced increases in Km values concomitant with decreasing equivalents of metal ion added are only observed in the presence of Mg2+ ions. PMID- 1417733 TI - Expression of ileal glucagon and peptide tyrosine-tyrosine genes. Response to inhibition of polyamine synthesis in the presence of massive small-bowel resection. AB - Massive small-bowel resection results in a marked adaptive response in the residual terminal ileum. Increased polyamine synthesis is a necessary component of this response. The ileal L-cell-derived peptides enteroglucagon and peptide tyrosine tyrosine (PYY) have been implicated as humoral mediators of this response. We have previously reported a rapid and sustained increase in glucagon mRNA concentrations after massive small-bowel resection. In this study using an inhibitor of the rate-limiting enzyme in polyamine biosynthesis, ornithine decarboxylase, we have demonstrated that the response of the glucagon and PYY genes to massive small-bowel resection is dependent on polyamine biosynthesis. In addition, we have examined the response of both the ornithine decarboxylase and c jun genes in this model of intestinal adaptation. PMID- 1417734 TI - Hyaluronan-binding region of aggrecan from pig laryngeal cartilage. Amino acid sequence, analysis of N-linked oligosaccharides and location of the keratan sulphate. AB - The hyaluronan-binding region (HABR) was prepared from pig laryngeal cartilage aggrecan and the amino acid sequence was determined. The HABR had two N-termini: one N-terminal sequence was Val-Glu-Val-Ser-Glu-Pro (367 amino acids in total), and a second N-terminal sequence (Ala-Ile-Ser-Val-Glu-Val; 370 amino acids in total) was found to arise due to alternate cleavage by the signal peptidase. The N-linked oligosaccharides were analysed by examining their reactivity with a series of lectins. It was found that the N-linked oligosaccharide on loop A was of the mannose type, while that on loop B was of the complex type. No reactivity was detected between the N-linked oligosaccharide on loop B' and any of the lectins. The location of keratan sulphate (KS) in the HABR was determined by Edman degradation of the immobilized KS-containing peptide. The released amino acid derivatives were collected and tested for the presence of epitope to antibody 5-D-4. On the basis of 5-D-4 reactivity and sequencing yields, the KS chains are attached to threonine residues 352 and 357. There is no KS at threonine-355. This site is not in fact in G1, but about 16 amino acid residues into the interglobular domain. Comparison of the structure of the KS chain from the HABR and from the KS domain of pig laryngeal cartilage aggrecan was made by separation on polyacrylamide gels of the oligosaccharides arising from digestion with keratanase. Comparison of the oligosaccharide maps suggests that the KS chains from both parts of the aggrecan molecule have the same structure. PMID- 1417735 TI - Sphingomyelin content of intestinal cell membranes regulates cholesterol absorption. Evidence for pancreatic and intestinal cell sphingomyelinase activity. AB - Micellar cholesterol uptake and secretion were investigated in the human intestinal cell line CaCo-2 following depletion of apical membrane sphingomyelin. The addition of exogenous sphingomyelinase, which hydrolysed 60% of prelabelled sphingomyelin, resulted in a 50% decrease in the uptake of cholesterol from bile salt micelles. The flux of membrane cholesterol into the cell by the hydrolysis of membrane sphingomyelin decreased the rate of cholesterol synthesis by 43% and inhibited hydroxymethylglutaryl-CoA reductase activity by 54%. Moreover, the rate of cholesterol esterification was increased 4-fold. Total cellular cholesterol mass was unchanged by the addition of sphingomyelinase; however, cholesteryl esters increased by 50% and the amount of unesterified cholesterol decreased significantly. The basolateral secretion of cholesterol mass was also decreased following sphingomyelin hydrolysis. Human pancreatic juice was found to contain neutral sphingomyelinase activity which required taurocholate for full expression. The presence of neutral sphingomyelinase activity was also documented in membranes prepared from CaCo-2 cells and in whole homogenates from human duodenal biopsies. The data suggest that the amount of sphingomyelin present in the apical membrane of the intestinal absorptive cell regulates cholesterol uptake from bile salt micelles. Sphingomyelinase activity within intestinal cells and in pancreatic juice could alter the sphingomyelin content of brush-border membranes of small intestinal absorptive cells and thus regulate the amount of cholesterol absorbed by the gut. PMID- 1417736 TI - Isolation and characterization of the promoter for the gene coding for the 68 kDa carnitine palmitoyltransferase from the rat. AB - Carnitine palmitoyltransferase (CPT) regulates the flux of long-chain fatty acids into the mitochondria for subsequent beta-oxidation. A 485 bp segment of the promoter for the gene encoding the 68 kDa CPT was isolated from a rat lambda DASH genomic library using the polymerase chain reaction. The promoter contained a consensus binding sequence for CREB (cyclic AMP response element binding protein) at -153 to -166, and for C/EBP alpha (CCAAT/enhancer binding protein) at -115 to 128. DNAase I footprinting using proteins isolated from rat liver nuclei indicated the presence of several regions of nuclear protein binding, most notably at -95 to -130, at -273 to -295, and at a wide region encompassing -395 to -465. DNAase I footprinting studies with purified CREB and C/EBP alpha confirmed that protein binding to DNA occurred at the sites predicted by the consensus sequences. The segment containing 481 bp of 5' flanking sequence plus 181 bp of untranslated mRNA was ligated to the structural gene for chloramphenicol acetyltransferase (CAT). When this plasmid was transfected into Hep G2 cells, CAT activity was stimulated 7-fold by addition of 1 mM-8-bromo cyclic AMP (8-Br-cAMP) or co-transfection of the expression vector coding for the catalytic subunit of protein kinase A (PKA). The ability of several known second messengers and transcription factors to stimulate transcription of 68 kDa CPT promoter-CAT reporter was tested in co-transfection experiments. 68 kDa CPT promoter-CAT reporter transcription activity was stimulated 7-fold by addition of 8-Br-cAMP, and this induction was depressed 50% by the addition of phorbol esters. When the 68 kDa CPT promoter-CAT reporter was co-transfected with an expression vector for CREB or C/EBP alpha, transcription was increased 3- and 10 fold respectively. 8-Br-cAMP caused an additional 8-fold induction in the presence of each factor to yield 25- and 80-fold induction respectively. Co transfection of the expression vector for c-jun also increased the CAT activity driven by the 68 kDa CPT promoter, while co-transfection with the expression vector for c-fos had no effect. When expression vectors for both c-jun and c-fos were co-transfected with the 68 kDa CPT promoter, c-fos depressed the induction seen with c-jun alone. PMID- 1417737 TI - Quantification of the accumulation and degradation of beta-very-low-density lipoproteins in vivo using a 19F-containing residualizing label and n.m.r. spectroscopy. AB - beta-Very-low-density lipoproteins (beta-VLDL)O were conjugated to the 19F containing residualizing label, NN-dilactitol-3,5-bis(trifluoromethyl)benzylamine (DLBA), to determine whether the metabolism of this lipoprotein fraction could be characterized in vivo with n.m.r. spectroscopy. Solution state 19F high resolution n.m.r. spectroscopy of DLBA-beta-VLDL, containing either intact apoproteins or selectively enzymically digested products, demonstrated that the extent of degradation could be distinguished by differences in spin-spin relaxation times (T2 times). DLBA-beta-VLDL was injected intravenously into rabbits, and accumulation of 19F in hepatic tissue was quantified non-invasively by n.m.r. spectroscopy 5 and 30 h after injection. In addition to quantifying the accumulation of DLBA-beta-VLDL in hepatic tissue, a marked decrease (approx. 100 Hz) in the linewidth of 19F resonance from labelled lipoproteins was observed at 30 h compared with the 5 h interval in continuously monitored animals. The change in linewidth was consistent with a decrease in molecular size that occurred during protein degradation, resulting in increased T2 times. To demonstrate that T2 times can be used as an index to quantify apoprotein degradation in vivo, relaxation measurements were performed on livers excised 20 h after injection of DLBA-beta-VLDL into rabbits. Two molecular motional fractions were revealed by relaxation profiles representing either an intact or an extensively degraded form of apoprotein. The amplitudes of each component were compared with results from trichloroacetic acid precipitation of liver homogenates acquired from rabbits 20 h after injection of beta-VLDL labelled with the radioiodinated analogue of DLBA, dilactitol-125I-tyramine. The amount of degraded apoprotein determined by n.m.r. spectroscopy and acid precipitation was 68.6 +/- 7.0% and 58.7 +/- 7.5% (n = 4) respectively. The results of this study demonstrate that 19F n.m.r. spectroscopy can be used to define the temporal characteristics of the hepatic metabolism of lipoproteins in vivo by quantifying both the tissue-specific accumulation and extent of apoprotein degradation. The methodology developed offers promise for the non-invasive, sequential and longitudinal evaluation of lipoprotein metabolism in vivo. PMID- 1417738 TI - Decreased affinity of recombinant antithrombin for heparin due to increased glycosylation. AB - Recombinant antithrombin produced by baby hamster kidney (BHK) or Chinese hamster ovary (CHO) cells was separated into two fractions, containing comparable amounts of protein, by affinity chromatography on matrix-linked heparin. Fluorescence titrations showed that the more tightly binding fraction had a heparin affinity similar to that of plasma antithrombin (Kd approximately 20 nM), whereas the affinity of the more weakly binding fraction was nearly 10-fold lower (Kd approximately 175 nM). Analyses of the heparin-catalysed rate of inhibition of thrombin further showed that the fractions differed only in their affinity for heparin and not in the intrinsic rate constant of either the uncatalysed or the heparin-catalysed inactivation of thrombin. The recombinant antithrombin fraction with lower heparin affinity migrated more slowly than both the fraction with higher affinity and plasma antithrombin in SDS/PAGE under reducing conditions, consistent with a slightly higher apparent relative molecular mass. This apparent size difference was abolished by the enzymic removal of the carbohydrate side chains from the proteins. Such removal also increased the heparin affinity of the weakly binding fraction, so that it eluted from matrix-linked heparin at a similar position to the deglycosylated tightly binding fraction or plasma antithrombin. Analyses of N-linked carbohydrate side chains showed that the weakly binding fraction from CHO cells had a higher proportion of tetra-antennary and a lower proportion of biantennary oligosaccharides than the tightly binding fraction. We conclude that the recombinant antithrombin produced by the two cell lines is heterogeneously glycosylated and that the increased carbohydrate content of a large proportion of the molecules results in a substantial decrease in the affinity of these molecules for heparin. These findings are of particular relevance for studies aimed at characterizing the heparin-binding site of recombinant antithrombin by site-directed mutagenesis. PMID- 1417739 TI - Partial purification and characterization of the sodium-ion-coupled 5 hydroxytryptamine transporter of rat cerebral cortex. AB - A procedure for the extensive purification of the Na(+)-coupled 5 hydroxytryptamine transporter of rat cerebral cortex has been developed. The 5 hydroxytryptamine transporter was solubilized with the non-ionic detergent digitonin, and the detergent extracts were subjected to sequential affinity chromatography on a citalopram-based agarose support and wheat-germ-agglutinin Sepharose. 5-Hydroxytryptamine transporters in the affinity-purified preparation were identified by using the selective 5-hydroxytryptamine-uptake inhibitor [3H]paroxetine, and were shown to display a similar pharmacological profile to those present in particulate preparations. An overall transporter purification of around 2000-fold was achieved with a 9% recovery. SDS/PAGE of affinity chromatographed material starting from detergent extracts incubated in the presence or absence of 1 mM-citalopram indicated that a polypeptide of M(r) 73,000 corresponded to the 5-hydroxytryptamine-transporter protein. PMID- 1417740 TI - Interaction between protein kinase C and Exo1 (14-3-3 protein) and its relevance to exocytosis in permeabilized adrenal chromaffin cells. AB - The roles of protein kinase C (PKC) and Exo1 in exocytosis from digitonin permeabilized adrenal chromaffin cells were explored by using exogenous purified proteins in a run-down/reconstitution system. The stimulatory action of Exo1 on exocytosis from run-down cells was found to be completely dependent on the continuous presence of exogenous MgATP, suggesting that it acts on the slow phase of exocytosis [Holz, Bittner, Peppers, Senter & Eberhard (1989), J. Biol. Chem. 264, 5412-5419]. Partially purified rat brain PKC was found to be able to stimulate Ca(2+)-dependent exocytosis from run-down cells in a dose-dependent manner. This effect was indeed due to PKC and not a contaminant in the PKC fraction, since the PKC activator phorbol 12-myristate 13-acetate (PMA), under conditions in which control secretion was not affected, potentiated the effect of the exogenous PKC in stimulating secretion. Furthermore, although either PKC or Exo1 alone could stimulate exocytosis from run-down cells, the effect of combining the fractions was synergistic, as had previously been observed using PMA treatment combined with Exo1 incubation [Morgan & Burgoyne (1992) Nature (London) 355, 833-836]. The observed synergy between PKC and Exo1 was not due to PKC-mediated phosphorylation of Exo1, and Exo1 was found not to affect PKC activity in enzyme assays. We conclude that PKC and Exo1 act synergistically in the slow phase of Ca(2+)-dependent exocytosis from adrenal chromaffin cells. Furthermore, PKC does not directly affect Exo1, but rather enhances the activity of Exo1 by a putative phosphorylation of another, unidentified, component of the exocytotic machinery which facilitates the action of Exo1 in exocytosis. PMID- 1417741 TI - Permeability of rat liver microsomal membrane to glucose 6-phosphate. AB - Light-scattering measurements of osmotically induced changes in the size of rat liver microsomal vesicles pre-equilibrated in a low-osmolality buffer revealed the following. (1) The increase in extravesicular osmolality by addition of glucose 6-phosphate or mannose 6-phosphate (25 mM each) caused a rapid shrinking of microsomal vesicles. After shrinkage, a rapid swelling phase (t1/2 approx. 22 s) was present with glucose 6-phosphate but absent with mannose 6-phosphate, indicating that the former had entered microsomal vesicles, but the latter had not. (2) Almost identical results were obtained in the absence of any glucose 6 phosphate hydrolysis, i.e. with microsomes pre-treated with 100 microM-vanadate. (3) The anion-channel blocker 4,4'-di-isothiocyanostilbene-2,2'-disulphonic acid (DIDS) suppressed the glucose 6-phosphate-induced swelling phase. (4) The swelling phase was more prolonged as the glucose 6-phosphate concentration increased (t1/2 = 16 +/- 3, 22 +/- 3 and 35 +/- 4 s with 25 mM, 37.5 mM- and 50 mM-glucose 6-phosphate respectively). The behaviour of glucose-6-phosphatase activity of intact and disrupted microsomes measured in the presence of high concentrations (less than 30 mM) of substrate also indicated the saturation of the glucose 6-phosphate permeation system by extravesicular concentrations of glucose 6-phosphate higher than 20-30 mM. Additional experiments showed that vanadate-treated microsomes pre-equilibrated with 0.1 mM- and 1.0 mM-glucose 6 phosphate (and [1-14C]glucose 6-phosphate as a tracer) rapidly (t1/2 less than 20 s) released [1-14C]glucose 6-phosphate when diluted in a glucose 6-phosphate-free medium. The efflux of [1-14C]glucose 6-phosphate was largely prevented by DIDS, allowing an evaluation of the intravesicular space of glucose 6-phosphate of approx. 1.0 microliter/mg of microsomal protein. PMID- 1417743 TI - Human interleukin-5 expressed in Escherichia coli has N-terminal modifications. AB - Recombinant human interleukin-5 exists as four major isoforms all possessing N terminal methionine. Peptide mapping and subsequent analysis by fast-atom bombardment mass spectrometry (f.a.b.-m.s.) have shown that N-terminal modifications are the cause of the charge heterogeneity. In order of decreasing abundance, these are unmodified methionine, retention of N-terminal formyl group, oxidation of N-terminal methionine to sulphoxide and carbamoylation of the N terminus. These results were confirmed by analysis of the reduced and alkylated intact protein by electrospray-ionization mass spectrometry. The implications of these findings for the production and characterization of recombinant proteins are briefly discussed. PMID- 1417742 TI - Partial characterization of natural and recombinant human soluble CD23. AB - The purification to homogeneity of an active soluble 25 kDa fragment of CD23, produced in insect cells using the baculovirus expression system, is described. Peptide mapping and analysis by Edman degradation and mass spectrometry permitted partial characterization of the protein. A total of 165 out of 172 residues, including N-terminal and C-terminal regions, were mapped. The positions of the two disulphide bonds in the IgE-binding region were also determined: residue 110 is joined to residue 124, and residue 42 to residue 133. Natural CD23 25 kDa fragment was also analysed and found to possess the same disulphide bond arrangement. These results extend the previously noted sequence similarity with lectins to elements of secondary structure. PMID- 1417744 TI - The activity and subcellular distribution of the peroxisomal enzyme acyl-CoA oxidase in human blood platelets. AB - The peroxisomal enzyme acyl-CoA oxidase is localized in the 'dense-tubular-system enriched fraction', probably identical with the endoplasmic reticulum, in human blood platelets. This localization is strongly different from the localization of catalase which seems to be a cytosolic enzyme, in agreement with Marcus, Zucker Franklin, Safir & Ullman [(1966) J. Clin. Invest. 45, 14-28]. A localization of acyl-CoA oxidase in the endoplasmic reticulum seems to be in good accordance with the important role of peroxisomes in the metabolism of prostaglandins, as recently demonstrated by Diczfalusy, Kase, Alexson & Bjorkhem [(1991) J. Clin. Invest. 88, 978-984]. PMID- 1417745 TI - Two distinct transcriptional activities of pea (Pisum sativum) chloroplasts share immunochemically related functional polypeptides. AB - An RNA polymerase activity has been purified from pea (Pisum sativum) chloroplast extracts with a distinct transcriptional specificity for a chloroplast messenger gene. This activity (ms-RNA pol) differs from the pea RNA polymerase preparation reported by Sun, Shapiro, Wu & Tewari [(1986) Plant Mol. Biol. 6, 429-439], which specifically transcribes only the rRNA gene (rb-RNA pol). The specificity of transcription has been assessed by the synthesis in vitro of discrete transcripts of predicted sizes using cloned promoter regions of the chloroplast psbA and 16 S rRNA genes. The ms-RNA pol preparation, with polypeptides ranging in apparent molecular mass from 22 to 180 kDa, correctly initiates transcription from recombinant plasmids containing the psbA promoter and does not support 16 S rRNA promoter-directed transcription. The two activities differ also in their response to Mn2+ ions. To investigate whether the two transcriptional activities share common functional polypeptides, monoclonal antibodies were developed against the rb-RNA pol preparation. Three clones were selected on the basis of their ability to inhibit transcription in vitro of the 16 S rRNA gene by rb-RNA pol. The antibodies from these clones independently recognized three polypeptides with molecular masses of 27, 90 and 95 kDa on immunoblots. Antibodies cross-reacting with the 90 kDa polypeptide completely eliminated the specific retardation of an end-labelled 16 S rRNA promoter fragment in a mobility-shift assay, whereas the antibodies against the 95 kDa polypeptide resulted in the formation of a ternary complex (enzyme-DNA-antibody). The antibodies cross-reacting with the 27 kDa polypeptide, however, did not alter the mobility of the retarded DNA-enzyme complex on the gel. These antibodies also inhibited transcription in vitro of the psbA gene by ms-RNA pol and recognized polypeptides of identical molecular masses in the ms-RNA pol. These results show that the three polypeptides are functional components of the chloroplast transcriptional complex and appear to be involved in the transcription of both rRNA and mRNA genes. Transcriptional specificity is probably conferred by ancillary transcription factor(s) which remain to be identified. PMID- 1417746 TI - A cortical phosphoprotein ('PP63') sensitive to exocytosis triggering in Paramecium cells. Immunolocalization and quenched-flow correlation of time course of dephosphorylation with membrane fusion. AB - We had previously shown that a phosphoprotein of 63 kDa ('PP63') is rapidly and selectively dephosphorylated during synchronous (less than or equal to 1 s) trichocyst exocytosis in Paramecium cells and then rephosphorylated within less than or equal to 1 min [Zieseniss & Plattner (1985) J. Cell Biol. 101, 2028 2035]. Using a new quenched-flow device, we now find a strict correlation between PP63 dephosphorylation and the process of membrane fusion, both occurring within 80 ms. Uptake of 32P over 90 min, followed by exocytosis and rephosphorylation for 1 min, results in a rather selective phosphorylation of the dephosphorylated form, P63, to PP63. Solubilization by repeated freezing and thawing allows isolations of P63 and PP63. On isoelectric focusing autoradiograms they have pI values of 6.05, 5.95 (major spots), 5.85 and 5.75. All spots are sensitive to alkaline, but not to acidic, hydrolysis (except for the pI-6.05 spot). On two dimensional-gel autoradiograms the most prominent spot, of pI 5.95, is most extensively de- and re-phosphorylated. This spot, from de- and re-phosphorylated samples, was used to produce monospecific antibodies. A cortical localization of PP63 was revealed by producing Western blots from isolated cell-surface fragments ('cortices') and by immunofluorescence labelling. We assume that both P63 and PP63 are attached to cortical structures, e.g. around trichocysts, though they are partly soluble. This localization and the strict correlation of PP63 dephosphorylation with exocytotic membrane fusion suggests a role in fusion regulation. PMID- 1417747 TI - Effect of side-chain amide thionation on turnover of beta-lactam substrates by beta-lactamases. Further evidence on the question of side-chain hydrogen-bonding in catalysis. AB - Two side-chain-thionated beta-lactams, a penicillin and a cephalosporin, have been prepared and found to be not significantly poorer as substrates of typical serine (classes A and C) beta-lactamases than are their oxo analogues. This result is interpreted to mean that any hydrogen-bonding site on these enzymes for the beta-lactam side-chain amide carbonyl group must be flexible and is more likely to be a passive rather than active or essential feature of the active site. Previously, data from crystal structures and site-directed mutagenesis had suggested that the side chain of Asn-132 of class-A beta-lactamases, a component of the conserved SDN loop, forms a hydrogen bond with the side-chain carbonyl of the beta-lactam substrate and may provide significant transition-state stabilization during catalysis. The thionocephalosporin was also equally as good as its oxo analogue as a substrate of the class-B beta-lactamase II of Bacillus cereus and not significantly less effective as an inhibitor of the Streptomyces R61 DD-peptidase; a tight hydrogen-bond donor site for the beta-lactam side-chain amide is apparently not present in these enzymes either. PMID- 1417748 TI - The metabolism of tetradecylthiopropionic acid, a 4-thia stearic acid, in the rat. In vivo and in vitro studies. AB - The metabolism of [1-14C]tetradecylthiopropionic acid (TTP), a 4-thia stearic acid, and its sulphoxide, [1-14C]texadecylsulphoxypropionic acid (TTP-SO), has been studied in intact rats, in isolated rat hepatocytes, and in rat liver mitochondria. Two pathways of oxidation (beta-oxidation and omega-oxidation) have been demonstrated. TTP is incorporated, in vivo, into tissue triacylglycerol and phospholipids, it is oxidized to CO2, and it is excreted in urine, mainly as carboxypropylsulphoxypropionic acid and a little as carboxymethylsulphoxypropionic acid. TTP-SO is metabolized, in vivo, more rapidly to the same two omega-oxidation products. In hepatocytes TTP is incorporated into triacylglycerol and phospholipids even more rapidly than stearic acid. It is recovered mainly in the 1-position of phosphatidylcholine. Some is oxidized to CO2 and acid-soluble products. TTP-SO is mainly omega-oxidized to the same metabolites as are found in urine. A small fraction is incorporated into phospholipids or oxidized to CO2. In isolated mitochondria [1-14C]TTP is converted into 14CO2, radioactive malonic semialdehyde, and addition products of malonic semialdehyde. In the presence of phenylhydrazine, malonic semialdehyde phenylhydrazone is the dominating product. In soluble extracts of mitochondria [1 14C]malonic semialdehyde is oxidized directly to 14CO2 in the presence of CoA and NAD+, probably by the (methyl)malonic acid semialdehyde dehydrogenase (EC 1.2.1.27). PMID- 1417749 TI - A study of the stabilization of tetrahedral adducts by trypsin and delta chymotrypsin. AB - delta-Chymotrypsin has been alkylated by 1-13C- and 2-13C-enriched tosylphenylalanylchloromethane. In the intact inhibitor derivative, signals due to the 1-13C- and 2-13C-enriched carbon atoms have chemical shifts which titrate from 55.10 to 59.50 p.p.m. and from 99.10 to 103.66 p.p.m. respectively with similar pKa values of 8.99 and 8.85 respectively. These signals are assigned to a tetrahedral adduct formed between the hydroxy group of serine-195 and the inhibitor. An additional signal at 58.09 p.p.m. and at 204.85 p.p.m. in the 1-13C and 2-13C-enzyme-inhibitor derivatives respectively does not titrate when the pH is changed and it is assigned to alkylated methionine-192. On denaturation/autolysis of the 1-13C-enriched enzyme-inhibitor derivative these signals associated with the intact inhibitor derivative are no longer detected, and a new signal, which titrates from 56.28 to 54.84 p.p.m. with a pKa of 5.26, is detected. The titration shift of this signal is assigned to the deprotonation of the imidazolium cation of alkylated histidine-57 in the denatured/autolysed enzyme-inhibitor derivative. Model compounds which form stable hydrates and hemiketals in aqueous solutions have been synthesized. By comparing the 13C titration shifts of these model compounds with those of the 13C enriched trypsin- and delta-chymotrypsin-inhibitor derivatives, we deduce that, in both of the intact enzyme-inhibitor derivatives, the zwitterionic tetrahedral adduct containing the imidazolium cation of histidine-57 and the hemiketal oxyanion predominates at alkaline pH values. It is estimated that in both the trypsin and delta-chymotrypsin-inhibitor derivatives the concentration of this zwitterionic tetrahedral adduct is 10,000-fold greater than it would be in water. We conclude that the pKa of the oxyanion of the hemiketal in the presence of the imidazolium cation of histidine-57 is 7.9 and 8.9 in the trypsin and delta-chymotrypsin inhibitor derivatives respectively and that the pKa of the imidazolium cation of histidine-57 is greater than 7.9 and greater than 8.9 when the oxyanion is present as its conjugate acid, whereas, when the oxyanion is present, the pKa of the imidazolium cation is greater than 11 in both enzyme-inhibitor derivatives. We discuss how these enzymes preferentially stabilize zwitterionic tetrahedral adducts in the intact enzyme-inhibitor derivatives and how they could stabilize similar tetrahedral intermediates during catalysis. It is suggested that substrate binding could raise the pKa of the imidazolium cation of histidine-57 before tetrahedral-intermediate formation which would explain the enhanced nucleophilicity of the hydroxy group of serine-195.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1417751 TI - Turnover of glycogen phosphorylase in the pectoralis muscle of broiler and layer chickens. AB - Glycogen phosphorylase is a major sarcoplasmic protein in chicken pectoralis muscle, constituting approx. 4% of the total protein complement. In slow-growing layer chicks phosphorylase accumulated in parallel with muscle accretion, but in fast-growing broiler chicks the concentration of phosphorylase in the muscle increased (from 5 to 8 mg/g wet wt.) with time. In a 5-week period, the total amount of phosphorylase in the pectoralis muscles increased 18-fold in broiler chicks (from approx. 75 to 1400 mg total), but only 3-fold (from approx. 100 to 270 mg total) in layers. Pyridoxal phosphate, the cofactor of the enzyme glycogen phosphorylase, was used as a specific label to measure the rate of degradation of the enzyme in the pectoralis muscle of growing broiler and layer chickens in vivo. In young animals, the fractional rate of phosphorylase synthesis was similar in broiler and layer chickens (approx. 15%/day), but the rate of degradation in layers (5%/day) was 5-fold higher than in broilers (1%/day). As the animals aged, the rate of synthesis decreased, but more so in layers than in broilers. The rate of degradation of phosphorylase also decreased in layers, but in broilers it remained at the low level seen in young animals. The dramatically higher rate of phosphorylase accretion in the pectoralis muscles of the broilers is therefore achieved by an initial lower rate of degradation combined with a sustained difference between rates of synthesis and degradation. PMID- 1417750 TI - Rat epididymal luminal fluid acid beta-D-galactosidase optimally hydrolyses glycoprotein substrate at neutral pH. AB - Several glycosidases, purified and characterized from mammalian tissues, have been shown to be optimally active under acidic conditions when p-nitrophenyl (PNP) or 4-methylumbelliferyl glycosides are used as substrates. Although high levels of the glycosidases are present in the epididymal lumen, their physiological role remains uncertain. To be functional, the glycosidases are expected to be enzymatically active at or near the physiological pH of luminal fluid. In this report, we demonstrate that the rat epididymal luminal fluid beta D-galactosidase, optimally active toward PNP beta-D-galactoside at pH 3.5, shows maximum activity towards a glycoprotein substrate ([Gal-3H]fetuin) at neutral pH. Several lines of evidence, including immunoprecipitation studies using antibody to the acid beta-D-galactosidase, and substrate competition studies, indicate that PNP galactosidase and [3H]Gal galactosidase activities are caused by a single enzyme, and that the two substrates are probably cleaved by the same catalytic site(s). Competition studies with various disaccharides indicate that this enzyme is capable of cleaving a variety of galactose linkages found in both O- and N-linked oligosaccharides. Molecular-sieve column chromatography of the beta-D-galactosidase of luminal fluid under several conditions of buffer and pH show that, whereas the enzyme eluted as a tetramer (apparent M(r) 320,000) under acidic conditions (pH 3.5-4.3), only dimers and monomers (apparent M(r) 180,000 and 92,000 respectively) were observed in neutral conditions (pH 6.8). This aggregation/dissociation phenomenon is reversible. These studies indicate that beta-D-galactosidase is present in the luminal fluid in dissociated forms, and is therefore optimally active towards glycoprotein substrates at physiological pH. The potential role of the enzyme in modification of sperm surface glycoproteins is discussed. PMID- 1417752 TI - Characterization of a human class-Theta glutathione S-transferase with activity towards 1-menaphthyl sulphate. AB - A purification scheme is described for a glutathione S-transferase (GST) from human liver that catalyses the conjugation of 1-menaphthyl sulphate (MS) with GSH; the method devised results in an approx. 500-fold increase in specific activity towards MS. The human enzyme which metabolizes MS is a homodimer comprising subunits of M(r) 25,100, and immunochemical experiments have shown it to be a member of the class-Theta GSTs. Automated Edman degradation of this enzyme has confirmed that it is a Theta-class GST bu the amino acid sequence obtained differs from that of GST theta described previously [Meyer, Coles, Pemble, Gilmore, Fraser & Ketterer (1991) Biochem. J. 274, 409-414]. We have therefore designated the enzyme that catalyses the conjugation of MS with GSH GST T2-2* (in the absence of complete amino acid sequence data, the T1 and T2 subunits are provisionally designated T1* and T2*); the evidence which indicates that GST theta (which should possibly now be called GST T1-1*) and GST T2-2* represent distinct isoenzymes is discussed. PMID- 1417753 TI - Clearance from plasma of lymph chylomicrons and chylomicron remnants labelled with 125I-tyramine-cellobiose. AB - The aims of the present study were to evaluate the metabolism of chylomicrons (CM) and of CM remnants after labelling with radioactive iodine and converting the iodinated CM into remnants in vitro. Lymph CM were radiolabelled with 125I or sham-labelled with 127I by either the ICl procedure or the tyramine-cellobiose (TC) procedure, then injected into rats. The clearance from plasma of the iodinated CM was compared with control non-iodinated lipid-labelled CM. After iodination with ICl, the plasma removal of endogenously labelled CM was significantly different from non-iodinated CM, with increased uptake of CM triacylglycerols by the liver. In contrast, the clearances from plasma and the uptake by organs of radiolabelled lipids of CM iodinated by the TC method (TC-CM) were similar to control CM. About 40% of the label from 125I-TC-CM was insoluble in 50% propan-2-ol, indicating association with CM apolipoprotein B48. Only about 8% of label was lipid soluble, mostly in phosphatidylethanolamine. Radioactivity from 125I-TC-CM injected intravenously in rats was cleared rapidly and by 30 min only 20% remained in plasma, whereas 48% was recovered in the liver. After fractionation of the plasma by density-gradient ultracentrifugation, most label remained associated with d (relative density) less than 1.006 lipoproteins. In intact rats label was also found associated with the low-density and high-density lipoprotein fractions of plasma. When the liver was excluded from circulation, the recovery of label in low-density- and high-density-lipoprotein fractions was greatly decreased. CM remnants were prepared in vivo by injecting 125I-TC-CM into functionally hepatectomized donors and compared with remnants prepared in vitro by incubation with purified bovine milk lipoprotein lipase. Although remnants prepared in vitro cleared from plasma slower than remnants prepared in vivo, the size, lipid composition and apolipoprotein profile on gradient PAGE of the remnants were similar. We conclude that labelling of CM by the TC method avoided the 'artefactual' changes in metabolism seen after labelling by the ICl procedure. CM remnants when prepared in vitro using lipoprotein lipase were found to be similar to those prepared in vivo after injection into functionally hepatectomized rats. PMID- 1417754 TI - Thrombin promotes actin polymerization in U937 human monocyte-macrophage cells. Analysis of the signalling mechanisms mediating actin polymerization. AB - The U937 human monocyte-macrophage cell line was used to examine the effect of thrombin, an ill-defined chemoattractant, on the polymerization of actin, a process essential for cell motility. In differentiated macrophage-like U937 cells, thrombin (0.5-50 units/ml) caused a rapid dose-dependent increase in the formation of filamentous (F-) actin, detected by the staining of F-actin with the fluorescent toxin, 7-nitrobenz-2-oxa-1,3-diazole-phallacidin. In contrast with other chemoattractants such as N-formylmethionyl-leucylphenylalanine or C5a, actin polymerization in response to thrombin occurred via a pertussis-toxin insensitive G1-(inhibitory G-protein) independent signalling pathway. Further, this response was not affected by the Ca2+ chelator EGTA or by the specific protein kinase C (PKC) inhibitor RO-31-8220. The response to thrombin was not mimicked by the Ca2+ ionophore ionomycin or by the direct PKC activator phorbol 12-myristate 13-acetate. The thrombin response was, however, inhibited by the non specific protein kinase inhibitor staurosporine. The present results suggest that in U937 cells thrombin stimulates the formation of F-actin via a signalling pathway independent of (i) the activation of PKC, (ii) the mobilization of intracellular Ca2+ and (iii) the activation of Ca(2+)-dependent protein kinases, but dependent on the activation of an undefined staurosporine-sensitive protein kinase. PMID- 1417755 TI - Kinetic and inhibition studies on catechol-O-methyltransferase affinity labelling by N-(3,4-dihydroxyphenyl)maleimide. AB - Initial velocity and product inhibition studies have been performed on soluble catechol-O-methyltransferase which has been partially purified from pig liver. The results are consistent with an ordered reaction mechanism, in which S adenosyl-L-methionine (AdoMet) is the leading substrate. The enzyme is irreversibly inhibited by maleimide derivatives in a biphasic manner, which suggests a differential reaction with two thiol groups. N-(3,4 Dihydroxyphenyl)maleimide, which has a reactive moiety (maleimide ring) and an affinity moiety (catechol ring), acts as an affinity labelling compound on the more reactive SH group; AdoMet and Mg2+ protect against this modification. Total protection of this SH group results in a pseudo-first-order inhibition of the enzyme, with the apparent rate constant being proportional to the inhibitor concentration. All the other maleimide derivatives studied inhibited the enzyme by reacting with one of the two SH groups in a non-specific manner. The reaction of the other, more reactive, SH group was either specific (active-site-directed) or non-specific, depending on the substituent present in the affinity moiety and also on the length of an intermediate chain of methylene groups present between this moiety and the reactive maleimide ring. In the presence of both AdoMet and Mg2+, 3,5-dinitrocatechol, a reversible inhibitor of the enzyme which is competitive with respect to the catechol substrate, protects the enzyme from inactivation by any of the maleimide derivatives. The adducts of these maleimide derivatives formed with dithiothreitol inhibit the enzyme reversibly, showing inhibition patterns that are consistent with the mechanism deduced from the initial velocity and product inhibition studies. PMID- 1417756 TI - A novel keratan sulphate proteoglycan from a human embryonal carcinoma cell line. AB - We describe here the purification and partial characterization of a 200 kDa keratan sulphate proteoglycan found in the pericellular matrix of human embryonal carcinoma cells. Previously we have shown that this molecule is recognized by a monoclonal antibody (GCTM-2). The antigen was isolated using ion-exchange chromatography and gel filtration, purification being monitored by e.l.i.s.a. using GCTM-2. Metabolic labelling of GCT 27 C-4 embryonal carcinoma cells with sodium [35S]sulphate resulted in the incorporation of [35S]sulphate into the purified molecule. Throughout the purification procedure, the peaks of 35S radioactivity were coincident with the peaks of immunoreactivity, and this label was released both by digestion with keratanase and chondroitinase, confirming the proteoglycan nature of the antigen. The intact molecule ran as a single broad band of 200 kDa, which has been identified by silver staining and immunoblotting following gel electrophoresis. Amino acid analysis of the purified antigen indicated a high content of serine, glycine and aspartic acid/asparagine residues. Visualization by rotary-shadowing electron microscopy suggests that the purified material forms large aggregates, even under denaturing conditions. Deglycosylation of this preparation with trifluoromethanesulphonic acid yielded a major band of 55 kDa and a minor band of 48 kDa. The biochemical nature of the molecule described here, along with tissue distribution studies using GCTM-2, indicates that the antigen is not related to previously described keratan sulphate proteoglycans. PMID- 1417758 TI - Metabolite channeling versus free diffusion: reinterpretation of aldolase catalysed inactivation of glyceraldehyde-3-phosphate dehydrogenase. PMID- 1417759 TI - Lysosomal handling of cystine residues: stoichiometry of cysteine involvement. PMID- 1417757 TI - Identification and characterization of aminopeptidases from Aplysia californica. AB - Aminopeptidase activities were identified in extracts of kidney, ovotestis, head ganglia, heart and haemolymph of Aplysia californica. These enzyme preparations hydrolysed [3H][Leu]enkephalin at the Try-1-Gly-2 bond as determined by h.p.l.c. analysis of cleavage products. In all these tissues, enkephalin-degrading aminopeptidase activities were present both in membrane-bound and cytosolic fractions. The bivalent-cation-chelating agent, 1,10-phenanthroline, inhibited kidney membrane aminopeptidase activity with an IC50 of 30 microM, suggesting that this enzyme is a metalloproteinase. The aminopeptidase inhibitor amastatin was the most potent inhibitor of [Leu]enkephalin degradation (IC50 25 nM) by membrane-bound aminopeptidase, and bacitracin, bestatin and puromycin were about 100-1000 times less potent. In contrast with membrane-bound aminopeptidase, the cytosolic form is sensitive to puromycin. Angiotensin-converting enzyme inhibitor had no effect on [Leu]enkephalin degradation by kidney membranes, while the neutral endopeptidase inhibitors were poor inhibitors of the enzymes in this preparation. The Km values of the aminopeptidase in the kidney membranes and cytosolic fractions for the [Leu]enkephalin substrate were 2.4 and 7.4 microM respectively. The aminopeptidase present in the kidney membranes also hydrolysed endogenous Phe-Met-Arg-Phe-amide peptide at the Phe-1-Met-2 bond as well as synthetic alanine p-nitroanilide and leucine p-nitroanilide. When used in a competition assay, these substrates inhibited hydrolysis of [3H][Leu]enkephalin, suggesting that the same enzyme degraded all these substrates. Taken together, these results suggest that Aplysia tissues contain both a membrane-bound aminopeptidase related to the mammalian aminopeptidase N and a cytosolic puromycin-sensitive aminopeptidase. PMID- 1417760 TI - Primary and predicted secondary structure of the Actinomadura R39 extracellular DD-peptidase, a penicillin-binding protein (PBP) related to the Escherichia coli PBP4. PMID- 1417763 TI - Respiratory control and substrate effects in the working rat heart. AB - 31P n.m.r. spectroscopy was used to measure the concentration of phosphates commonly proposed to control oxidative phosphorylation. The effect of loading conditions, beta-adrenergic stimulation and different substrates (acetate, pyruvate or glucose) was examined under steady-state conditions in the isolated working rat heart. Oxygen consumption and haemodynamic variables were monitored continuously. In response to a 2-fold increase in afterload, there were no significant changes in [ADP], [ATP]/[ADP], or [ATP]/[ADP][Pi]. In the presence of isoprenaline, these variables also tended not to change from afterload. However, isoprenaline, at identical perfusion pressures, consistently decreased the phosphorylation potential and [ATP]/[ADP], but had little effect on [ADP]. Substrates altered the phosphate metabolites in a manner independent of oxygen consumption, and had only minor effects on the relationship between phosphates and work, in contrast with other studies. Thus, metabolites of ATP synthesis are not normally involved in respiratory control. The 31P n.m.r. spectrum can vary greatly, but does not predict oxygen consumption in this preparation. Substrates have no effect on the mechanism of respiratory control. Thus the normal control of respiration in the heart at steady state cannot occur at the level of its substrates. Rather, there must be concerted regulation of the numerous pathways, involving allostery and covalent modification. The attention of future research should be shifted away from the metabolites of ATP and towards identifying the effectors of such regulation. PMID- 1417762 TI - Conformational stability of bovine alpha-crystallin. Evidence for a destabilizing effect of ascorbate. AB - Short-term incubation of bovine alpha-crystallin with ascorbate alters the protein conformational stability. The denaturation curves with urea and guanidinium-chloride show different patterns, suggesting a deviation from a two state mechanism owing to the presence of one or more intermediates in the unfolding of ascorbate-modified alpha-crystallin. Furthermore, the latter protein profiles are shifted to lower denaturant concentrations indicating a destabilizing action of ascorbate, which is capable of facilitating protein dissociation into subunits as demonstrated by gel filtration with 1.5 M-urea. The decrease in conformational stability cannot be ascribed to any major structural alteration, but rather to localized changes in the protein molecule. In fact, no difference between native and ascorbate-treated alpha-crystallin can be detected by amino acid analysis but perturbation of the tryptophan and tyrosine environment is indicated by alterations in intrinsic fluorescence. Furthermore, turbidity and light-scattering measurements suggest an involvement of the lysine side chains, since aggregability patterns with acetylsalicylic acid are significantly altered. The ascorbate-destabilizing effect on the conformational stability of alpha-crystallin, probably exerted through oxidative modification of amino acid residues and/or the formation of covalent adducts, provokes unfavourable steric interactions between residues along the polypeptide chains, thus favouring aggregation and insolubilization of crystallins which can lead to cataract formation, as also demonstrated by proteolytic digestion patterns which show a lower rate of degradation of the ascorbate-modified alpha-crystallin. PMID- 1417764 TI - Substrate specificity of the purine-2'-deoxyribonucleosidase of Crithidia luciliae. AB - The purine-2'-deoxyribonucleosidase of Crithidia luciliae catalyses an efficient deoxyribosyl transfer between a variety of purine bases, benzimidazole and 5,6 dimethylbenzimidazole. Since the deoxyriboside of a deoxyribosyl acceptor is necessarily also a substrate, the trans-N-deoxyribosylase activity of the enzyme allows a study of its specificity to be extended to a large number of purines and purine analogues. Amongst 27 different deoxyribosyl acceptors, only hypoxanthine gave rise to isomeric products. The introduction of methyl groups at appropriate positions in either purine or benzimidazole lowered the Michaelis constant, KB, for deoxyribosyl acceptors: by about 10-fold for 6-methylpurine (KB 351 +/- 87 microM) compared with purine (KB 3.91 +/- 0.8 mM) and by about 10(3)-fold for 5,6 dimethylbenzimidazole (KB 7.0 +/- 0.79 microM) compared with benzimidazole (Km,app. 7.8 +/- 2.4 mM). The maximal rates of deoxyribosyl transfer to different acceptors, on the other hand, varied by only 4.5-fold, and can be ascribed to decreases in the rate of release of the newly formed purine deoxyriboside from the enzyme. PMID- 1417761 TI - Nuclear protein phosphorylation and growth control. PMID- 1417765 TI - Release of cell surface proteoglycans from differentiating colon cells proceeds by cleavage of lipophilic anchor peptides. AB - Heparan sulphate proteoglycans are rapidly released from VACO 10MS colon cancer cells that are triggered with phorbol esters to undergo terminal differentiation. This lag-free temperature-sensitive process is correlated with a conversion of the lipophilic proteoglycans of the cell surface into non-lipophilic proteoglycans that accumulate in the culture medium. The released proteoglycans are very similar to their lipophilic precursors in size, buoyant density and glycosaminoglycan characteristics; however, they exhibit slightly smaller core proteins after chemical and enzymic deglycosylation. The lipophilicity of the larger-sized core proteins of the cell-associated proteoglycans is also correlated with the presence of an easily iodinatable domain; this domain is missing in the released proteoglycans. Exogenous proteases (i.e. chymotrypsin, V8, trypsin and proteinase K) readily cleave this segment from the larger protease-resistant region of the proteoglycan structure. It is also released intact by treatment of the isolated proteoglycans with methanolic HCl. This component appears to be peptide in character, in that proteases readily degrade it and release iodotyrosines when the precursor has been iodinated. No evidence for the presence of covalently attached fatty acids in the cell-associated proteoglycans was found. These results are consistent with the hypothesis that the altered proteoglycan metabolism that is associated with the phorbol-ester induced terminal differentiation of certain human colon cancer cells ensues upon the activation of a membrane-localized protease that cleaves a lipophilic anchor segment from the cell surface proteoglycans. PMID- 1417766 TI - Evidence for cytochrome b5 as an electron donor in ricinoleic acid biosynthesis in microsomal preparations from developing castor bean (Ricinus communis L.). AB - The major b-type cytochrome in microsomal membrane preparations from developing endosperm of castor bean (Ricinus communis) was cytochrome b5. Cytochrome P-450 was also present. The microsomal membranes had delta 12-hydroxylase activity and catalysed the NAD(P)H-dependent hydroxylation of oleate to yield ricinoleic acid. CO had no effect on the hydroxylase activity. Rabbit polyclonal antibodies were raised against the hydrophilic cytochrome b5 fragment purified from cauliflower (Brassica oleracea) floret microsomes. The anti-(cytochrome b5) IgG inhibited delta 12-hydroxylase, delta 12-desaturase and cytochrome c reductase activity in the microsomes. The results indicate that electrons from NAD(P)H were transferred to the site of hydroxylation via cytochrome b5 and that cytochrome P-450 was not involved. PMID- 1417767 TI - Steady-state kinetic analysis of aldehyde dehydrogenase from human erythrocytes. AB - The steady-state kinetics of purified cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) from human erythrocytes have been studied at 37 degrees C. Previous studies of the enzyme from several mammalian sources, which used a lower assay temperature, have been difficult to interpret because of the substrate activation by acetaldehyde which led to complex kinetic behaviour. At 37 degrees C the initial-rate data do not depart significantly from Michaelis-Menten kinetics. Studies of the variation of initial rates as a function of the concentrations of both substrates and studies of the inhibition by NADH were consistent with a sequential mechanism being followed. High-substrate inhibition by acetaldehyde was competitive with respect to NAD+. The enzyme was not inhibited by the product acetate and thus the results of these studies, although consistent with an ordered mechanism in which NAD+ was the first substrate to bind, were inconclusive. That such a mechanism was followed was confirmed by determination of the initial-rate behaviour in the presence of acetaldehyde and glycolaldehyde as alternative substrates. When the reciprocal of the initial rate of NADH formation was plotted against the acetaldehyde concentration at a series of fixed ratios between that substrate and glycolaldehyde, a linear 'mixed inhibition' pattern was obtained, confirming the mechanism to be ordered with NAD+ being the leading substrate and with kinetically significant ternary complex-formation. PMID- 1417769 TI - Prokaryotic triterpenoids: O-alpha-D-glucuronopyranosyl bacteriohopanetetrol, a novel hopanoid from the bacterium Rhodospirillum rubrum. AB - A novel hopanoid bearing a glucuronopyranosyl residue linked via an alpha glycosidic bond to the hydroxyl group of C-35 in bacteriohopanetetrol was isolated, from the type strain of Rhodospirillum rubrum as well as from a mutant lacking blue carotenoid. PMID- 1417768 TI - ATPase-inhibitor proteins of brown-adipose-tissue mitochondria from warm- and cold-acclimated rats. AB - 1. A group of male Sprague-Dawley rats (5-6 weeks old) was cold-acclimated at 4 degrees C for 4 weeks. Warm-acclimated controls remained at 24 degrees C. Total protein content of brown adipose tissue (BAT) increased more than 3-fold and total uncoupling protein (UCP) content increased more than 6-fold upon cold acclimation. The concentration of UCP in isolated BAT mitochondria almost doubled. 2. Specific ATPase activity of the non-thermogenic BAT mitochondria (from warm-acclimated controls) was low and increased about 6-fold on addition of 1 microM-Ca2+, which raised free Ca2+ levels (measured by Fura-2) in the incubation media from 1.32 +/- 0.28 microM (mean +/- S.E.M.) to 2.29 +/- 0.39 microM [at which the Ca(2+)-binding ATPase-inhibitor protein (CaBI) is inactivated]. Correspondingly, the specific ATP synthetase activity of the non thermogenic BAT mitochondria was high and was decreased by 74% by addition of 1 microM-Ca2+. 3. In contrast, specific ATPase activity of thermogenic BAT mitochondria (from cold-acclimated rats) was 5 times that of the control group, and addition of Ca2+ had only a small stimulatory response. Correspondingly, the specific ATP synthetase activity of the thermogenic BAT mitochondria was low, and the decrease by Ca2+ was small, albeit significant. 4. Extracts of BAT mitochondria from both groups of animals contained significant amounts of the ATPase-inhibitor protein of Pullman and Monroy (PMI) as well as of CaBI, as shown by gel electrophoresis. Kinetic studies of inhibition of mitochondrial ATPase activity showed that PMI activity was unaltered in extracts from the thermogenic BAT mitochondria, whereas CaBI activity was slightly but significantly increased. 5. The presence of active ATPase-inhibitor proteins in BAT mitochondria was shown for the first time. We conclude that uncoupling of oxidative phosphorylation occurs in thermogenic BAT mitochondria, even in the presence of the ATPase inhibitor proteins. PMID- 1417770 TI - Gene expression of calpains and their specific endogenous inhibitor, calpastatin, in skeletal muscle of fed and fasted rabbits. AB - To investigate the role of calpains in myofibrillar protein degradation in skeletal muscle and the regulation of their activity in vivo, we studied the effects of fasting on gene expression of calpains and calpastatin in the skeletal muscle of rabbits. In response to fasting, myofibrillar protein degradation increased 2-fold and mRNA levels of calpain I, calpain II and calpastatin were also increased. However, calpain and calpastatin activities remained unchanged. To investigate this discrepancy, we analysed polysomal calpain mRNA. Results indicated that fasting caused a 2-fold increase in the loading of calpain I and II mRNAs on ribosomes. Thus transcription of genes encoding calpain may be increased during fasting to ensure adequate synthesis of the proteinases needed to mobilize muscle protein reserves. The effect of fasting on calpain and calpastatin mRNA expression is shared by cathepsin D and proteasome C2 but not by beta-actin, implying that fasting invokes control of several proteolytic systems in skeletal muscle and underscores the possibility that each proteolytic system plays a role in the adaptation of skeletal muscle to the fasted state. PMID- 1417771 TI - Small-angle X-ray-scattering studies of the C hordeins of barley (Hordeum vulgare). AB - Small angle X-ray scattering was used to study the solution conformation of the C hordeins of barley (Hordeum vulgare), a group of proteins whose primary structure consists predominantly of an octapeptide repeat motif. Measurements on the protein in 0.1 M-acetic acid at 25 degrees C are consistent with a model for the protein conformation of a stiff coil, the so-called 'worm-like' chain. The characteristic parameters (the Kuhn statistical segment length and the contour length) of the protein were calculated as 5.11 and 71.5 nm respectively. PMID- 1417772 TI - The predominant calcimedins from Trypanosoma brucei comprise a family of flagellar EF-hand calcium-binding proteins. AB - The cellular complement of calcimedins was identified in Trypanosoma brucei by Ca(2+)-dependent association with phenyl-Sepharose. Predominant calcimedins with molecular mass of 23-26 kDa and 44 kDa, along with minor calcimedins of 96, 120 and 230 kDa, were obtained. The trypanosome calcimedins were unrelated to vertebrate annexins, based upon antibody cross-reactivity and an inability to associate in a Ca(2+)-dependent way with phospholipid vesicles comprised of phosphatidylserine or phosphatidylethanolamine/phosphatidylcholine (1:1, w/w). Partial sequence analysis demonstrated that 44 kDa calcimedin (Tb-44) contained an EF-hand calcium-binding loop. Five CNBr/tryptic fragments exhibited a total of 93% similarity with Tb-17, a 23 kDa EF-hand protein in T. brucei. The trypanosome calcimedins appeared to comprise a family of proteins, based on sequence similarities and antibody cross-reactivity of affinity-purified anti-Tb44 with the 23-26 kDa cluster. No evidence was found for Tb-44 in the related species T. cruzi, Leishmania taraentolae or Crithidia fasciculata. Antibodies against Tb-44 were localized by immunofluorescence along the flagellum of T. brucei. Immunoblot analysis of flagella-enriched preparations demonstrated that Tb-44 and the 23-26 kDa cluster were present in this structure. We conclude that annexin family members are not among the predominant trypanosome proteins that associate with phenyl-Sepharose in a Ca(2+)-dependent way. Instead, the major trypanosome calcimedins comprise a family of flagellar EF-hand calcium-binding proteins. PMID- 1417773 TI - Structurally and functionally conserved regions of cytochrome P-450 reductase as targets for DNA amplification by the polymerase chain reaction. Cloning and nucleotide sequence of the Schizosaccharomyces pombe cDNA. AB - 1. Alignments of the available cytochrome P-450 reductase amino acid sequences, and comparison with the crystal structure of ferredoxin-NADP reductase, indicate that two highly conserved regions are of functional importance. 2. Degenerate oligonucleotide primers, based on these sequences, were used in the polymerase chain reaction to amplify a 309 bp fragment of the cytochrome P-450 reductase gene from Schizosaccharomyces pombe for use as an homologous probe. 3. A 2.6 kb cDNA was cloned from a lambda library, and sequencing revealed an open-reading frame of 2034 bp encoding a protein of M(r) 76774. This protein shares 38-41% identity with other eukaryotic cytochrome P-450 reductases, and 30% identity with that of Bacillus megaterium. 4. Comparison of the N-terminal FMN-binding domain with flavodoxin, and the C-terminal FAD- and NADP-binding domain with ferredoxin NADP reductase, indicates the presence of several functionally conserved regions. 5. The Sc. pombe cytochrome P-450 reductase gene was shown to contain no introns. PMID- 1417774 TI - Biosynthesis of heparin. The D-glucuronosyl- and N-acetyl-D glucosaminyltransferase reactions and their relation to polymer modification. AB - Oligosaccharides with the general structure [GlcA-GlcNAc]n-GlcA-aMan (aMan is 2,5 anhydro-D-mannose), derived from the Escherichia coli K5 capsular polysaccharide, were found to serve as monosaccharide acceptors for a GlcNAc-transferase, solubilized from a mouse mastocytoma microsomal fraction and implicated in heparin biosynthesis. Digestion of these oligosaccharides with beta-D glucuronidase yielded acceptors for the GlcA-transferase that acts in concert with the GlcNAc-transferase. Assays based on the oligosaccharide acceptors showed broad pH optima for the two enzymes, centred around pH 6.5 for the GlcNAc transferase and around pH 7.0 for the GlcA-transferase. The GlcNAc-transferase showed an absolute requirement for Mn2+, whereas the GlcA-transferase was stimulated by Ca2+ and Mg2+ but not by Mn2+. The GlcNAc acceptor ability of the [GlcA-GlcNAc]n-GlcA-aMan oligosaccharides increased with increasing chain length, as reflected by the apparent Km, which was 60 microM for a hexasaccharide but 6 microM for a hexadecasaccharide. By contrast, the Km for [GlcNAc-GlcA]n-aMan oligosaccharides in the GlcA-transferase reaction was higher, approximately 0.5 mM, and unaffected by acceptor size. After chemical modification of the oligosaccharides to obtain mixed N-substituents (N-unsubstituted, N-acetylated or N-sulphated GlcN residues), GlcNAc transfer was found to be virtually independent of the N-substituent pattern of the acceptor sequence. The GlcA-transferase, on the other hand, showed marked preference for an acceptor with a non-reducing terminal GlcNAc-GlcA-GlcNSO3- sequence, which would thus have a lower Km for the enzyme than the corresponding fully N-acetylated structure. These results, along with our previous finding that chain elongation in a mastocytoma microsomal system is strongly promoted by concomitant N-sulphation of the nascent chain [Lidholt, Kjellen & Lindahl (1989) Biochem. J. 261, 999-1007], raise the possibility that the glycosyltransferases and the N-deacetylase/N sulphotransferase act in concert during chain elongation, assembled into an enzyme complex. PMID- 1417775 TI - Further characterization of the N-terminal copper(II)- and nickel(II)-binding motif of proteins. Studies of metal binding to chicken serum albumin and the native sequence peptide. AB - We have investigated the Cu(II)- and Ni(II)-binding properties of chicken serum albumin (CSA) and of the native sequence tripeptide derived from the N-terminus of this protein. Spectrophotometric and equilibrium dialysis experiments demonstrate that Cu(II) and Ni(II) bind non-specifically at the N-terminus of CSA. Proton displacement studies show that the histidine residue in the fourth position of the protein does not appear to participate in the binding of the two metals. Consistent results were obtained with the native sequence tripeptide L aspartyl-L-alanyl-L-glutamic acid N-methylamide. The results presented here demonstrate that neither the glutamic acid residue in the third position nor the histidine in the fourth position participate in the binding of Cu(II) and Ni(II) to CSA. It is known, however, that a number of other albumins with a histidine residue in the third position possess high-affinity Cu(II)- and Ni(II)-binding sites. Our results provide further evidence that the N-terminal Cu(II)/Ni(II) binding motif requires a histidine at the third position in order to bind Cu(II) and Ni(II) specifically. PMID- 1417776 TI - Isolation of cDNA clones for a 50 kDa glycoprotein of the human erythrocyte membrane associated with Rh (rhesus) blood-group antigen expression. AB - The Rh blood-group antigens are associated with human erythrocyte membrane proteins of approx. 30 kDa (the Rh30 polypeptides). Heterogeneously glycosylated membrane proteins of 50 and 45 kDa (the Rh50 glycoproteins) are coprecipitated with the Rh30 polypeptides on immunoprecipitation with anti-Rh-specific mono- and poly-clonal antibodies. We have isolated cDNA clones representing a member of the Rh50 glycoprotein family (the Rh50A glycoprotein). We used PCR with degenerate primers based on the N-terminal amino acid sequence of the Rh50 glycoproteins and human genomic DNA as a template and cloned and sequenced three types of PCR product of the expected size. Two of these products, Rh50A and Rh50B, gave the same translated amino acid sequence which corresponded to the expected Rh50 glycoprotein sequence but had only 75% DNA sequence similarity. The third product (Rh50C) contained a single base deletion, and the translated amino acid sequence contained an in-frame stop codon. We have isolated cDNA clones containing the full coding sequence of the Rh50A glycoprotein. This sequence predicts that it is a 409-amino acid N-glycosylated membrane protein with up to 12 transmembrane domains. The Rh50A glycoprotein shows clear similarity to the Rh30A protein in both amino acid sequence and predicted topology. Our results are consistent with the Rh30 and Rh50 groups of proteins being different subunits of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane. We mapped the Rh50A gene to human chromosome 6p21-qter, showing that genetic differences in the Rh30 rather than the Rh50 genes specify the major polymorphic forms of the Rh antigens. PMID- 1417777 TI - Phospholipid molecular species composition of mouse liver nuclei. Influence of dietary n-3 fatty acid ethyl esters. AB - The effect of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl esters on the individual molecular species composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined in mouse liver nuclei. After a 10 day feeding period, there was a depletion of the sn-2 position of n-6 polyunsaturated fatty acids (PUFA) and substitution with n-3 PUFA. EPA feeding significantly increased (P less than 0.05) diacyl PC and PE 16:0-20:5, n-3, 16:0-22:6,n-3, 18:0-20:5,n-3 and 18:0-22:6,n-3 relative to control (safflower oil ethyl ester fed) animals. In comparison, DHA feeding significantly increased (P less than 0.05) 22:6 n-3-containing species, specifically 18:1-22:6,n-3, 16:0-22:6,n-3 and 18:0-22:6,n-3 in PC, and 18:1 22:6,n-3, 16:0-22:6,n-3 and 18:0-22:6,n-3 in PE. In addition, the presence of 18:0-20:5,n-3 PC in the nuclei of DHA-fed rats and of 18:2-20:5,n-3, 18:1-20:5,n 3 and 18:0-20:5,n-3 in nuclear PE indicate that incorporation of DHA retroconversion (22:6,n-3-->20:5,n-3) products. These results indicate both EPA and DHA are extensively incorporated into nuclear phospholipids, and therefore could potentially influence gene function. PMID- 1417778 TI - Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family. AB - We have previously reported the cloning of cDNAs for a flavin-containing mono oxygenase (FMO) of man, designated FMO1 [Dolphin, Shephard, Povey, Palmer, Ziegler, Ayesh, Smith & Phillips (1991) J. Biol. Chem. 266, 12379-12385], that is the orthologue of pig and rabbit hepatic FMOs. We now describe the isolation and characterization of cDNA clones for a second human FMO, which we have designated FMO2. The polypeptide encoded by the cDNAs is 558 amino acid residues long, has a calculated M(r) of 63337, and contains putative FAD- and NADP-binding sites that align exactly with those described in other mammalian FMOs. Human FMO2 has 51-53% primary sequence identity with human FMO1, rabbit pulmonary FMO and rabbit liver FMO form 2, and thus represents a fourth, distinct, member of the mammalian FMO family. The corresponding mRNA is present in low abundance in adult human liver. Southern blot hybridization with single-exon probes demonstrated that human FMO2 and FMO1 are the products of single genes. The gene encoding FMO2 (designated FMO2) was mapped, by the polymerase chain reaction, to human chromosome 1, the same chromosome on which FMO1 is located. PMID- 1417779 TI - Carbachol stimulation of phospholipase A2 and insulin secretion in pancreatic islets. AB - Arachidonic acid has been implicated as a second messenger in insulin secretion by islets of Langerhans. D-Glucose, the major physiological stimulus, increases unesterified arachidonate accumulation in islets. We now show, for the first time, that the muscarinic agonist carbachol, at concentrations which stimulate insulin secretion, causes a rapid and nearly 3-fold increase in arachidonic acid accumulation in islets. The combination of glucose and carbachol has an additive effect on unesterified arachidonate release. There is a large component of secretagogue-induced arachidonate accumulation that is independent of extracellular Ca2+. Carbachol stimulation of arachidonic acid release is mediated by activation of phospholipase A2, as demonstrated by early increases in endogenous lysophosphatidylcholine. In addition to phospholipase A2 activation, carbachol-induced arachidonic acid accumulation also appears to involve diacylglycerol hydrolysis, since the diacylglycerol lipase inhibitor RG80267 partly inhibited arachidonic acid accumulation. In contrast, glucose-induced arachidonic acid accumulation appears to reflect diacylglycerol hydrolysis entirely. Our observations indicate that phospholipase A2 has an important role in muscarinic-induced insulin secretion. PMID- 1417780 TI - Characterization of the human properdin gene. AB - A cosmid clone containing the complete coding sequence of the human properdin gene has been characterized. The gene is located at one end of the approximately 40 kb cosmid insert and approximately 8.2 kb of the sequence data have been obtained from this region. Two discrepancies with the published cDNA sequence [Nolan, Schwaeble, Kaluz, Dierich & Reid (1991) Eur. J. Immunol. 21, 771-776] have been resolved. Properdin has previously been described as a modular protein, with the majority of its sequence composed of six tandem repeats of a sequence motif of approximately 60 amino acids which is related to the type-I repeat sequence (TSR), initially described in thrombospondin [Lawler & Hynes (1986) J. Cell Biol. 103, 1635-1648; Goundis & Reid (1988), Nature (London) 335, 82-85]. Analysis of the genomic sequence data indicates that the human properdin gene is organized into ten exons which span approximately 6 kb of the genome. TSRs 2-5 are coded for by discrete, symmetrical exons (phase 1-1), which supports the hypothesis that modular proteins evolved by a process involving exon shuffling. TSR1 is also coded for by a discrete exon, but the boundaries are asymmetrical (phase 2-1). The sequence coding for the sixth TSR is split across the final two exons of the gene with the first 38 amino acids of the repeat coded for by an asymmetric exon (phase 1-2). This split at the genomic level has been shown, by alignment analysis, to be reflected at the protein level with the division of repeat 6 into TSR-like and TSR-unlike sequences. PMID- 1417781 TI - cDNA cloning and sequence analysis of human pancreatic procarboxypeptidase A1. AB - Using polyclonal antibodies raised against human pancreatic procarboxypeptidases, a full-length cDNA coding for an A-type proenzyme was isolated from a lambda gt11 human pancreatic library. This cDNA contains standard 3' and 5' flanking regions, a poly(A)+ tail and a central region of 1260 nucleotides coding for a protein of 419 amino acids. On the basis of sequence comparisons, the human protein was classified as a procarboxypeptidase A1 which is very similar to the previously described A1 forms from rat and bovine pancreatic glands. The presence of the amino acid sequences assumed to be of importance for the zymogen inhibition by its activation segment, primarily on the basis of the recently reported crystal structure of the B form, further supports the proposed classification. PMID- 1417782 TI - Structure of the bovine ETB endothelin receptor gene. AB - The structure of the gene encoding the bovine type B endothelin receptor (ETB) has been established and compared with those of other heptahelical receptors. The gene is present as a single copy in the bovine genome, as demonstrated by Southern blot analysis, and spans at least 36 kb. The coding region is divided into 7 exons separated by 6 introns, one of which is more than 23 kb in length. The exons correspond well to the structural domains of the receptor: the first exon encodes the first and second transmembrane domains, and each of the following transmembrane domains is encoded by a separate exon. The portion of the ETB protein sequence encoded by exon 3 is quite different from the corresponding ETA sequence, suggesting that this region is responsible for the distinct ligand specificities of the two receptor subtypes. The second intron interrupts the canonical Asp-Arg-Tyr sequence, which is located at the end of the third transmembrane domain of the heptahelical receptors, as with the substance P, substance K, dopamine D2 and dopamine D3 receptor genes. To map the 5' region of the gene and determine the start of transcription, primer-extended cDNAs were cloned and sequenced: multiple start sites were deduced with no apparent TATA box in the expected upstream region. Similar results were obtained by ribonuclease protection analysis. PMID- 1417783 TI - Stimulation of phosphatidate synthesis in endothelial cells in response to P2 receptor activation. Evidence for phospholipase C and phospholipase D involvement, phosphatidate and diacylglycerol interconversion and the role of protein kinase C. AB - To investigate the stimulation of phosphatidic acid formation in bovine aortic endothelial cells by P2-purinergic agonists, we labelled AG4762 cells with [32P]P1 and stimulated in the presence of butanol. Under these conditions phospholipase D generated [32P]phosphatidylbutanol, whereas the [32P]phosphatidic acid from phospholipase C and diacylglycerol kinase was unchanged. The action of various purinergic agonists on both [32P]phosphatidic acid and [32P]phosphatidylbutanol was consistent with the presence of a P2Y receptor. The stimulation of phospholipase D was dependent on extracellular Ca2+ and was mostly transient (completed within 3 min), whereas the initial stimulation of phospholipase C was independent of extracellular Ca2+, followed by a Ca(2+) dependent phase. The agonist stimulation of phospholipase D was dependent on protein kinase C, as judged by its sensitivity to the relatively selective protein kinase C inhibitor Ro 31-8220. These results show that purinergic receptor-mediated stimulation of phosphatidic acid has three phases: an initial Ca(2+)-independent stimulation of phospholipase C, an early but transient Ca(2+)- and protein kinase C-dependent stimulation of phospholipase D, and a sustained Ca(2+)-dependent stimulation of phospholipase C. Using propranolol to inhibit phosphatidate phosphohydrolase, we provide evidence that phosphatidic acid derived from purinergic-receptor-mediated stimulation of the phospholipase C/diacylglycerol kinase route can itself be converted back into diacylglycerol. PMID- 1417784 TI - Bovine colostrum CMP-NeuAc:Gal beta(1-->4)GlcNAc-R alpha(2-->6)-sialyltransferase is involved in the synthesis of the terminal NeuAc alpha(2-->6)GalNAc beta(1- >4)GlcNAc sequence occurring on N-linked glycans of bovine milk glycoproteins. AB - Bovine colostrum CMP-NeuAc:Gal beta(-->4)GlcNAc-R alpha(2-->6)-sialyltransferase (alpha 6-sialyltransferase) appears to be capable of catalysing alpha 6 sialylation of the disaccharide GalNAc beta(1-->4)GlcNAc to yield the trisaccharide NeuAc alpha(2-->6)GalNAc beta(1-->4)GlcNAc. This provides an enzymic basis for the occurrence of this sialylated structure on the N-linked glycans of a number of bovine milk glycoproteins. Competition experiments using Gal beta(1-->4)GlcNAc and GalNAc beta(-->4)GlcNAc as acceptors indicate that both substrates are recognized by a single active site on the alpha 6 sialyltransferase. Extrapolation of these results suggests that the NeuAc alpha(2 ->6)GalNAc beta(1-->4)GlcNAc structural element occurring on the N-linked glycans of several human glycoproteins are similarly synthesized by the action of a Gal beta(1-->4)GlcNAc-R alpha(2-->6)-sialyltransferase. PMID- 1417785 TI - Analysis and elimination of protein perturbation in infrared difference spectra of acyl-chymotrypsin ester carbonyl groups by using 13C isotopic substitution. AB - I.r. spectroscopy has been applied to the study of hydrogen-bonding of the unique ester carbonyl group of acylchymotrypsins in the oxyanion hole of the enzyme. This catalytic device provides electrophilic stabilization of negative charge in the transition states and tetrahedral intermediates along the reaction pathway. The use of 13C isotope substitution of the ester carbonyl group reinforces the previous observation [White & Wharton (1990) Biochem. J. 270, 627-637] that the ester carbonyl group is significantly polarized in the ground state by hydrogen bonding in the oxyanion hole. I.r. difference spectra of [carbonyl-12C]-minus [carbonyl-13C]-cinnamoyl-chymotrypsin as well as each of these acylenzymes minus free enzyme are reported. These spectra show that the contribution of protein perturbation (i.e. spectral features that arise from the enzyme which is distorted on acylation) in [carbonyl-12C]cinnamoyl-chymotrypsin minus free enzyme spectra is significant. The contribution of the perturbation components of the spectra is pH-dependent and can represent up to 50% of the total absorbance in the spectral region from 1690 to 1740 cm-1. Use of the isotopic difference method has allowed problems associated with protein perturbation to be eliminated. Similar difference spectra are presented for dihydrocinnamoyl-chymotrypsin. In this case the effect of perturbation is very marked and leads to the cancellation of the band assigned to the non-bonded conformation of the acyl group which has previously only been observed at higher pH. The isotopic difference method again proves reliable and shows that the frequency difference previously used to calculate the ground-state electronic strain induced by the oxyanion-hole catalytic device is not affected by the perturbation, although the amplitudes of the spectral features are different. A study of the deacylation of cinnamoyl chymotrypsin in water and deuterium oxide using both u.v. and i.r. spectroscopies has confirmed that the use of deuterium oxide as solvent has no serious effect on the deacylation behaviour of the enzyme. I.r. bands assigned to nonproductive and productive conformers decline identically during deacylation, which shows that the conformers are in dynamic exchange on the reaction time-scale. PMID- 1417786 TI - Comments on the kinetic analysis of enzyme reactions involving an unstable irreversible modifier. PMID- 1417787 TI - Making sense of the kinetics of reactions of unstable modifiers with enzymes. PMID- 1417789 TI - Identification of a dopamine-binding protein on the membrane of the human platelet. AB - The binding of [3H]dopamine to platelet membranes has been examined in an attempt to identify the putative dopamine-uptake mechanism of the platelet. [3H]Dopamine has been shown to bind to a 42,000 Da glycoprotein in platelet membrane with high affinity (Kd = 22.6 nM) and binding of [3H]dopamine was competed for by dopamine, molecules with catechol moieties, 5-hydroxytryptamine, GSH and ascorbic acid. Differences in pharmacological profile and molecular mass suggest that [3H]dopamine does not bind to a known receptor, a neuronal-type dopamine transporter or the platelet 5-hydroxytryptamine-uptake site. It is proposed that this novel binding site for dopamine, which has been purified 1000-fold from particulate platelet membrane, is likely to be a component of the dopamine-uptake mechanism of the human platelet. PMID- 1417788 TI - Characterization and identification of an epidermal-growth-factor-activated phospholipase A2. AB - The production of arachidonic acid (AA), which is involved in mitogenic signalling by epidermal growth factor (EGF), is most directly accomplished by the action of phospholipase A2 (PLA2). We demonstrate that EGF treatment of intact NEF cells rapidly activates a cytosolic PLA2, as measured in cell-free extracts by the release of radiolabelled AA from exogenously added 1-stearoyl-2-[1 14C]arachidonoyl phosphatidylcholine. Activation of PLA2 by EGF resulted in an enhanced Vmax. and no change in Km. The PLA2 activity was eluted in a single peak at 0.4 M-NaCl from a Mono Q anion-exchange column, and migrated with an approximate molecular mass of 70 kDa on a Superose 12 gel-filtration column. The EGF-activated PLA2 activity co-migrated with the basal PLA2 activity upon gel filtration, and persisted after partial purification, which indicates that the activation is due to a stable modification of the enzyme. The EGF-stimulated PLA2 is Ca(2+)-dependent, with maximal activity at micromolar concentrations of Ca2+, has a pH optimum at 9, associates with the particulate cell fraction in a Ca(2+) dependent fashion, and is selective for arachidonoyl at the sn-2 position. These data demonstrate the EGF-induced activation of a PLA2, which is similar to a recently cloned high-molecular-mass AA-selective cytosolic PLA2, thus providing a link between EGF-receptor tyrosine kinase activation and AA metabolism. PMID- 1417790 TI - Epidermal-growth-factor-induced production of phosphatidylalcohols by HeLa cells and A431 cells through activation of phospholipase D. AB - In response to epidermal growth factor (EGF), HeLa cells and A431 cells rapidly accumulate substantial amounts of phosphatidic acid (up to 0.16 and 0.2 micrograms/10(6) cells respectively), which represents approx. 0.17% of total phospholipid. Phosphatidic acid may be a potential product of diacylglycerol kinase and/or of phospholipase D. To evaluate the contribution of phospholipase D, the phosphatidyl-transfer reaction to a primary alcohol (mostly butan-1-ol; 0.2%) was measured; this reaction is known to be mediated exclusively by phospholipase D in intact cells. In HeLa and in A431 cells prelabelled with [1 14C]oleic acid, EGF (10 and 100 nM respectively) caused a 3-fold increase in radioactive phosphatidylbutanol within 5 min at the expense of labelled phosphatidic acid. Dose-response relationships showed 10 nM- and 100 nM-EGF to be maximally effective in HeLa cells and A431 cells respectively. Mass determinations showed that the phosphatidylbutanol formed within 5 min represented only part of the phosphatidic acid. Depletion of protein kinase C by pretreatment of A431 cells for 17 h with the phorbol ester phorbol 12-myristate 13-acetate (0.1 microM) did not impair EGF-induced formation of phosphatidylbutanol, thus indicating that the reaction was independent of this enzyme. Since phosphatidic acid is suggested to exert second-messenger functions as well as to induce biophysical changes in cellular membranes, its formation, including that via the phospholipase D pathway, may represent an important link between extracellular signals and intracellular targets. PMID- 1417791 TI - Intracellular pH and the stimulus-secretion coupling in insulin-producing RINm5F cells. AB - The regulation of intracellular pH (pHi) and its role in the insulin-secretory process were evaluated, by using the clonal insulin-secreting cell line RINm5F. Glyceraldehyde, lactate and dihydroxyacetone decreased pHi, but only the first two released insulin. In the presence of extracellular Na+ the cells counteracted the acidification. Blocking the Na+/H+ exchange in acidic cells resulted in a drastic further lowering of pHi, an effect not obtained under basal conditions. Whereas glyceraldehyde depolarized the cells, lactate was without effect. Dihydroxyacetone hyperpolarized the cells in the presence of extracellular Na+, but this effect disappeared when Na+ was excluded from the medium. Stimulation with glyceraldehyde resulted in increased free cytoplasmic Ca2+ concentration ([Ca2+]i). Dihydroxyacetone and lactate had no effect on [Ca2+]i in the presence of Na+, but lactate induced a decrease in [Ca2+]i in Na(+)-deficient medium. In RINm5F cells the activity of the Na+/H+ antiport could not be augmented by activation of protein kinase C (PKC). Hence, in insulin-secreting cells a PKC insensitive Na+/H+ antiport is the major mechanism restoring a decrease in pHi. Acidification itself does not affect membrane potential, but may directly interact with the mechanisms regulating exocytosis. PMID- 1417793 TI - The dependence of lipid monolayer lipolysis on surface pressure. AB - Bronsted-Bjerrum theory [Bronsted (1922) Z. Phys. Chem. 102, 169-207; (1925) Z. Phys. Chem. 115, 337-364; Bjerrum (1924) Z. Phys. Chem. 108, 82-100] as applied to reactions at interfaces is used to interpret published data on the lipolysis of dinonanoyl phosphatidylcholine monolayers by pancreatic phospholipase A2. Reasonable quantitative agreement between theoretical and experimental results occurs when the reported effects of surface pressure on the amount of adsorbed enzyme are used together with the assumption that the Langmuir-Syskowski [Lange (1967) Nonionic Surfactants (Schick, M., ed.), chap. 4, Marcel Dekker, London and New York] isotherm describes the adsorption of lipid. The equations of Mass Action kinetics are less successful. Equivalent data on the lipolysis of didodecanoyl phosphatidylglycerol by pancreatic lipase can also be interpreted by arguing that the adsorbed enzyme forms significant amounts of enzyme substrate complex which reacts to give products in accordance with the well-known Briggs Haldane [Lehninger (1975) Biochemistry, 2nd edn., chap. 8, Worth, New York] mechanism. The positions of the observed maxima in rate versus surface pressure plots suggests that the adsorption of an enzyme molecule displaces less lipid than one expects from the pronounced differences in molecular sizes of the two adsorbed species. PMID- 1417792 TI - Human neutrophil phospholipase D activation by N-formylmethionyl leucylphenylalanine reveals a two-step process for the control of phosphatidylcholine breakdown and oxidative burst. AB - A comparative study of real-time kinetics of respiratory burst, monitored by H2O2 dependent chemiluminescence, and phospholipase D (PLD)-mediated phosphatidylcholine breakdown has been undertaken on human neutrophils stimulated by N-formylmethionyl-leucylphenylalanine in the absence of cytochalasin B. The fungal metabolite 17-hydroxywortmannin (HWT), an inhibitor of NADPH oxidase activation, decreases phosphatidic acid (PA) production by 30% at a concentration of 1 nM. Higher concentrations (10 nM-1 microM) inhibit PA formation maximally by 50% as compared with control. In all cases, the inhibition is delayed by 20-30 s after addition of the agonist. Thus the full PA generation is actually the result of an early (HWT-insensitive) and a late (HWT-sensitive) phosphatidylcholine breakdown. However, under all conditions, alkylacylglycerol remains at the basal level. PLD activity is dependent on Ca2+ influx, but is fully inhibited in cells depleted of Ca2+ with EGTA and Quin 2. The effect of HWT on the respiratory burst was investigated by measuring the kinetics of H2O2-induced chemiluminescence. This method allows to distinguish various phases of superoxide ion production: a lag, an increase in H2O2 formation (early phase), the duration of H2O2 production (late phase) and the termination of the oxidative burst. The lag remains constant for all HWT concentrations. A concentration of 10 nM-HWT, which fully inhibits the HWT-sensitive part of PA production, decreases superoxide ion production with a delay of about 20 s after addition of the agonist. Higher HWT concentrations, which have no additional effect on PLD inhibition, equally affect an early and a late phase of the burst. Thus high doses of HWT have a site of action which decreases the whole burst but does not affect the PLD any more. Therefore HWT and Ca2+ provide evidence for a two-step process for PLD activation. Only the delayed PA generation is functionally linked to a late phase of the oxidative burst. PMID- 1417794 TI - Different triggers for calcium oscillations in mouse eggs involve a ryanodine sensitive calcium store. AB - Relative intracellular free Ca2+ concentrations ([Ca2+]i) were monitored in mature unfertilized mouse eggs by measuring fluorescence of intracellular fluo3. A number of different agents were found to cause sustained repetitive transient [Ca2+]i oscillations. These were microinjection of a cytosolic sperm factor, sustained injection of Ins-(1,4,5)P1, or extracellular addition of the thiol reagent thimerosal. Stimulating G-protein activity by injection of guanosine 5' [gamma-thio]triphosphate plus application of carbachol also caused [Ca2+]i oscillations, but less reliably than other stimuli. A role for Ca(2+)-induced Ca2+ release and a ryanodine-sensitive Ca2+ channel in mouse eggs was suggested by the finding that microinjection, or external addition, of ryanodine also caused [Ca2+]i increases. Furthermore, ryanodine, along with thimerosal, increased the sensitivity of eggs to Ca(2+)-induced [Ca2+]i oscillations. When ryanodine was added to eggs oscillating in response to the sperm factor, InsP3 or thimerosal, it caused a decrease in amplitude of oscillations and eventually a block of [Ca2+]i oscillations associated with a sustained elevation of [Ca2+]i. These data suggest that a ryanodine-sensitive Ca(2+)-release mechanism exists in mouse eggs and that a ryanodine-sensitive Ca2+ store plays a role in generating intracellular [Ca2+]i oscillations. PMID- 1417795 TI - Immunological detection of phenylalanine hydroxylase protein in Drosophila melanogaster. AB - A monoclonal antibody raised against monkey liver phenylalanine hydroxylase (PAH) has been used to detect this protein in Drosophila melanogaster. A cross-reacting material (CRM) band of apparent molecular mass 50-52 kDa, equivalent to that deduced for the Drosophila melanogaster PAH protein based on the pah gene cDNA sequence, has been detected. This CRM was analysed throughout development and showed an equivalent pattern to that reported for PAH activity in this insect, with maxima at pupariation and at pharate adult formation. Distribution of this CRM in larval tissues, the haemolymph and the adult body is mainly restricted to the larval fat body and the adult head. Demonstration of this CRM as the PAH protein comes from the correlation between the decreased PAH enzyme activities of two mutant strains and their decreased amounts of CRM by Western blotting. PMID- 1417797 TI - The human IGF-I gene contains two cell type-specifically regulated promoters. AB - The human insulin-like growth factor-I (IGF-I) gene contains two alternative leader exons: exons 1 and 2. We have identified, by transient transfection experiments, the putative promoters P1 and P2 upstream of these leader exons. The promoter regions were cloned in front of the luciferase reporter gene and their promoter activities were measured in transfected SK-N-MC (human neuroepithelioma) and OVCAR-3 (human ovarian carcinoma) cells. Both of these cell lines express the IGF-I gene endogenously, resulting in normally sized IGF-I mRNAs of 7.6, 1.3 and 1.1 kb. In SK-N-MC cells, in which P1 is the most active IGF-I promoter, P2 displayed a three times lower promoter activity than P1. However, in OVCAR-3 cells, P2 is four times more active than P1, resulting in an overall 12-fold difference in the relative promoter activities of the two IGF-I gene promoters in these two cell types. This indicates that the IGF-I promoters show a cell type specific expression pattern. PMID- 1417798 TI - Reverse transcription with nested polymerase chain reaction shows expression of basic fibroblast growth factor transcripts in human granulosa and cumulus cells from in vitro fertilisation patients. AB - Basic fibroblast growth factor (bFGF) is a potent angiogenic factor that has also been implicated in granulosa cell and oocyte maturation. We now report the expression of messenger ribonucleic acid (mRNA) encoding bFGF in human granulosa and cumulus cells obtained at oocyte recovery in in vitro fertilisation patients. It was necessary to use the sensitive technique of a nested polymerase chain reaction (PCR) after reverse transcription (RT) to detect transcripts. This finding in conjunction with a recent report showing the presence of transcripts for transforming growth factor beta (TGF beta) in the same type of cells by PCR indicates that mechanisms are in place for controlling extracellular proteolysis and cell differentiation. PMID- 1417796 TI - Evidence that beta-hydroxyacyl-CoA dehydrase purified from rat liver microsomes is of peroxisomal origin. AB - The present study provides strong evidence that the previously isolated hepatic microsomal beta-hydroxyacyl-CoA dehydrase (EC 4.2.1.17), believed to be a component of the fatty acid chain-elongation system, is derived, not from the endoplasmic reticulum, but rather from the peroxisomes. The isolated dehydrase was purified over 3000-fold and showed optimal enzymic activity toward beta hydroxyacyl-CoAs or trans-2-enoyl-CoAs with carbon chain lengths of 8-10. The purified preparation (VDH) displayed a pH optimum at 7.5 with beta hydroxydecanoyl-CoA, and at 6.0 with beta-hydroxystearoyl-CoA. Competitive inhibition studies suggested that VDH contained dehydrase isoforms, and SDS/PAGE showed three major bands at 47, 71 and 78 kDa, all of which reacted to antibody raised to the purified preparation. Immunocytochemical studies with anti-rabbit IgG to VDH unequivocally demonstrated gold particles randomly distributed throughout the peroxisomal matrix of liver sections from both untreated and di-(2 ethylhexyl) phthalate-treated rats. No labelling was associated with endoplasmic reticulum or with the microsomal fraction. Substrate-specificity studies and the use of antibodies to VDH and to the peroxisomal trifunctional protein indicated that VDH and the latter are separate enzymes. On the other hand, the VDH possesses biochemical characteristics similar to those of the D-beta-hydroxyacyl CoA dehydrase recently isolated from rat liver peroxisomes [Li, Smeland & Schulz (1990) J. Biol. Chem. 265, 13629-13634; Hiltunen, Palosaari & Kunau (1989) J. Biol. Chem. 264, 13536-13540]. Neither enzyme utilizes crotonoyl-CoA or cis-2 enoyl-CoA as substrates, but both enzymes convert trans-2-enoyl substrates into the D-isomer only. In addition, the VDH also contained beta-oxoacyl-CoA reductase (beta-hydroxyacyl-CoA dehydrogenase) activity, which co-purified with the dehydrase. PMID- 1417799 TI - Production of a low molecular weight growth inhibitory factor by adenovirus 12 transformed cells. AB - Malignant rodent cells transformed by human adenovirus 12 produce a potent cell growth inhibitory factor. The cell growth inhibitory factor inhibits the growth of and DNA synthesis in normal fibroblasts in vitro. Extent of the production of the cell growth inhibitory factor appears to be proportional to that of the malignancy of the transformed cells. C57AT1-AB cells, an adenovirus 12 transformant of C57BL/6 mouse origin, are highly tumorigenic in the syngeneic and allogeneic mice. The cell growth inhibitory factor produced by these cells was characterized for the physicochemical properties; the cell growth-inhibitory activity was quantitatively recovered in the filtrates of YM-2 membrane (M(r) less than 1,000), resistant to the heat treatments at 56 degrees C for 30 min and 100 degrees C for 5 min, and extractable by ethyl acetate under acid-condition. These results suggest that the cell growth inhibitory factor may be lipid or oligopeptides. PMID- 1417800 TI - Truncation of N-terminal extracellular or C-terminal intracellular domains of human ETA receptor abrogated the binding activity to ET-1. AB - We have investigated the function of N-terminal and C-terminal domains of the human ETA receptor by expressing truncated mutants in COS-7 cells. Three kinds of ETA receptors truncated in the N-terminal extracellular or C-terminal intracellular domains were produced. Deletion of the entire extracellular N terminal or intracellular C-terminal domain completely inactivated the ET-1 binding activity. However, the deletion of one half of the N-terminal extracellular domain of the ETA receptor, missing one of two N-linked glycosylation sites, maintained complete binding activity. Specific monoclonal antibodies detected all the truncated ETA receptors in the cell membrane fraction of transfected COS-7 cells. The size of the ETA receptor was heterogeneous due to differential glycosylation and distributed in 48K, 45K and 42K dalton bands in Western blot analysis. These results demonstrated that a part of the N-terminal domain in close proximity to the first transmembrane region is required for the ligand binding activity of the ETA receptor, and the C-terminal domain is perhaps necessary as an anchor for maintenance of the binding site. PMID- 1417801 TI - Protease inhibitors generate cytotoxic fragments from Alzheimer amyloid protein precursor in cDNA-transfected glioma cells. AB - A human glioma cell line (Bu-17) was stably transfected with full-length cDNA encoding beta/A4 amyloid protein precursor (APP). When the transfectants were treated with protease inhibitors (leupeptin, E-64, and antipain) and the lysosomotropic agent chloroquine, aberrantly processed fragments of APP having molecular sizes of 8-30 kDa were detected with an antibody against the carboxyl terminal sequence of APP. Immunocytochemistry revealed that these fragments were localized in the lysosome-like organelles. Treatment of the APP cDNA transfectants with chloroquine for 3 days caused cellular degeneration, and leupeptin and E-64 enhanced chloroquine-induced cytotoxicity. These results suggest that inhibition of lysosomal hydrolases impairs intracellular APP metabolism to generate aberrantly processed fragments that induce cytotoxicity. PMID- 1417802 TI - Inhibition of apoptosis by zinc: a reappraisal. AB - Apoptosis--or programmed cell death--is an active type of cell death, occurring in several pathophysiological conditions. One of the most important characteristics of apoptosis is that cell death is preceded by DNA fragmentation, consequent to the activation of nuclear calcium- and magnesium-dependent endonuclease(s). DNA fragmentation can be inhibited by zinc ions. By using several techniques, such as DNA agarose gel electrophoresis, cytofluorimetric analysis of DNA content and of cell cycle, 3H-thymidine incorporation and trypan blue dye exclusion test, we show that zinc, despite completely inhibiting DNA fragmentation and the consequent loss of nuclear DNA content, does not protect rat thymocytes from spontaneous or dexamethasone-induced death. Our data also suggest that DNA fragmentation, although characteristic, is not a critical event for thymocyte death of apoptotic type. PMID- 1417803 TI - Isolation and characterization of conglutinin as an influenza A virus inhibitor. AB - Normal horse and guinea pig sera contain alpha 2-macroglobulin which inhibits the infectivity and hemagglutinating activity of influenza A viruses of the H2 and H3 subtypes. On the other hand, normal bovine serum contains a component termed beta inhibitor that inhibits the infectivity and hemagglutinating activity of influenza A viruses of the H1 and H3 subtypes. To investigate the nature of the beta inhibitor of influenza A virus, we purified the conglutinin and examined its characteristics. First, we found a high correlation between the hemagglutination inhibition(HI) titer and conglutinin titer in several bovine sera (r = 0.906, p less than 0.005). The HI of bovine serum was mainly dependent on conglutinin because the HI activity was abrogated by N-acetylglucosamine but not by D mannose. The conglutinin, purified from bovine serum, had neutralizing-activity as well as HI activity on influenza A viruses of the H1 and H3 subtypes. The HI activity of conglutinin was heat stable (56 degrees C, 30 min), Ca(++)-dependent, and resistant to both neuraminidase and periodate treatments. The HI activity of purified conglutinin was blocked by N-acetylglucosamine but not by D-mannose. The conglutinin was bound to hemagglutinin which had high mannose and complex sugar chains and its binding was inhibited by N-acetylglucosamine and dependent on divalent cations. These data indicate that the beta-like inhibitor activity of bovine serum is mainly dependent on conglutinin which inhibits hemagglutination and neutralizes the virus infectivity by its binding to a carbohydrate site at the HA. PMID- 1417804 TI - Peptide analogs of the pseudosubstrate domain of smooth muscle myosin light chain kinase inhibit actomyosin ATPase activity at concentrations that do not inhibit superprecipitation. AB - The inhibitory effect of calmodulin antagonists, synthetic peptide analogs of the pseudosubstrate domain of smooth muscle MLC kinase, and an inhibitor based on the sequence of MLC were examined using bovine aortic actomyosin and isolated chicken gizzard MLC. Much lower concentrations of the peptides were necessary to inhibit actomyosin ATPase activity than to inhibit superprecipitation. In contrast, calmodulin antagonists inhibited both ATPase activity and superprecipitation at similar concentrations. The peptide analogs were competitive with isolated MLC, but not calmodulin, for inhibition of MLC kinase. These results suggest that in addition to the calmodulin dependence of MLC phosphorylation, a second calmodulin like protein may be important in actin-myosin interactions. The data also suggest that the pseudosubstrate hypothesis may not completely account for regulation of MLC kinase activity. PMID- 1417805 TI - Secretory processing of the Alzheimer amyloid beta/A4 protein precursor is increased by protein phosphorylation. AB - The 39-43 residue polypeptide (amyloid beta protein, beta A4) deposited as amyloid in Alzheimer's disease (AD) is derived from a set of 695-770 residue precursors referred to as the amyloid beta A4 protein precursor (beta APP). In each of the 695, 751, and 770 residue precursors, the 43 residue beta A4 is an internal peptide that begins 99 residues from the COOH-terminus of the beta APP. Each holoform is normally cleaved within the beta A4 to produce a large secreted derivative as well as a small membrane associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire beta A4 peptide. In this study, we employ cells stably transfected with full length beta APP695, beta APP751, or beta APP770 expression constructs to show that phorbol ester activation of protein kinase C substantially increases the production of secreted forms from each isoform. By increasing processing of beta APP in the secretory pathway, PKC phosphorylation may help to prevent amyloid deposition. PMID- 1417806 TI - Multiple growth factor mRNAs are expressed in chicken adipocyte precursor cells. AB - We have examined the expression of growth factor genes in primary cultures of chicken adipocyte precursors. RNA was extracted from proliferating and differentiated cells, reversed transcribed and amplified by PCR using gene specific primers. The identity of the PCR products was confirmed by restriction mapping. We show, for the first time, constitutive expression of TGF-beta 2, TGF beta 3, TGF-beta 4 and bFGF genes in chicken adipocyte precursors. We also detect GH-independent, but differentiation-dependent IGF-I gene expression. The synthesis and action of these growth factors supports the hypothesis that they act as autocrine and/or paracrine regulators of adipocyte precursor cell proliferation and differentiation. PMID- 1417808 TI - The primary structure of TE-6: a novel neuropeptide from the nematode Ascaris suum. AB - Extensive immunoreactivity (IR) towards a hexapeptide (sequence KGQELE), which flanks the C-terminus of the pancreastatin sequence in rat chromogranin A (CGA), is found throughout the nervous system of the nematode parasite Ascaris suum. The peptide IR was purified from the gonoduct of the parasite and found to have the sequence TKQELE. This peptide, designated TE-6, has some C-terminal homology with several regions of the CGA molecule. However, TE-6 was the only peptide isolated suggesting that either the nematode does not possess CGA, or that the -ELE regions of parasite CGA-like peptides which would be larger than TE-6 are not accessible to the antiserum in RIA, or are not being successfully extracted from the parasite. The N-terminus of TE-6 has little homology with any of the sequences preceding -ELE regions in CGA. This, and the fact that the tissue from which TE-6 was isolated does not contain IR towards another, highly conserved, region of the CGA molecule (WE-14) suggests that TE-6 may belong to a new class of regulatory peptide unrelated to CGA. PMID- 1417807 TI - Essential role of collagens for terminal differentiation of preadipocytes. AB - In order to study the role of collagens in the differentiation of TA1 preadipose cells in vitro, ethyl-3,4-dihydroxybenzoate (EDHB) was used as a specific inhibitor of collagen synthesis. The secretion of collagenous proteins only was severely decreased after exposure to EDHB, and this was accompanied by a decrease of differentiation as indicated by low activity levels of glycerophosphate dehydrogenase. The effect of EDHB was dose-dependent and also dependent upon the stage of cell differentiation. Northern-blot analysis show that EDHB addition to undifferentiated cells did not prevent the induction of A2COL6 gene, a marker of the preadipose state, but prevented the induction of the gene encoding for the adipocyte lipid binding protein and the modulation of the expression of the lipoprotein lipase gene which are both indicators of the adipose state. These results demonstrate that differentiation of preadipose cells into adipose cells requires active synthesis of collagens during the preadipose state. PMID- 1417809 TI - Cleavage of farnesylated COOH-terminal heptapeptide of mouse N-ras by brain microsomal membranes: evidence for a carboxypeptidase which specifically removes the COOH-terminal methionine. AB - Brain microsomal membranes are capable of sequentially removing Met, Leu and Val from a chemically synthesized COOH-terminal heptapeptide (propionyl-Gly-Ser-Pro (farnesyl-Cys)-Val-Leu-Met) of mouse N-ras protein. The carboxypeptidase generating Met displays maximum activity at neutral pH and shows high affinity for the farnesylated substrate (Km = 73 microM) as compared to its non farnesylated precursor (Km = 600 microM). The results of inhibitor action suggest that the membrane carboxypeptidase is a novel, probably thiol-dependent, serine type peptidase. PMID- 1417811 TI - Chloroacetates of 2- and 3-demethylthiocolchicine: specific covalent interactions with tubulin with preferential labeling of the beta-subunit. AB - We synthesized two chemically reactive A ring modified analogs of colchicine, 2 chloroacetyl-2-demethylthiocolchicine (2-CTC) and 3-chloroacetyl-3 demethylthiocolchicine (3-CTC). Both are similar to colchicine as inhibitors of tubulin polymerization and act as competitive inhibitors of colchicine binding (apparent Ki values, 3 microM). [14C]-labeled 2-CTC and 3-CTC bound to tubulin at 37 degrees C but not at 0 degree C, and bound drug formed covalent bond(s) with tubulin. The binding and covalent reactions were inhibited by podophyllotoxin. About 60% of the bound 3-CTC rapidly formed a covalent bond with tubulin. With 2 CTC the covalent reaction was slower than the binding reaction, and only one third of the bound 2-CTC reacted covalently with tubulin. The ratio of radiolabel in beta-tubulin to that in alpha-tubulin was about 4:1 with both 2-CTC and 3-CTC. PMID- 1417810 TI - CDw 60 antibodies bind to acetylated forms of ganglioside GD3. AB - Four monoclonal antibodies, M-T21, M-T32, M-T41 and UM4D4, which belong to the new CDw 60 cluster of antibodies specific for a subpopulation of human T lymphocytes, were found to bind mainly to acetylated forms of ganglioside GD3. After O-deacetylation of the antigen, binding was reduced ("M-T"-antibodies) or abolished (UM4D4). PMID- 1417812 TI - N,O-diacylated-N-hydroxyarylsulfonamides: nitroxyl precursors with potent smooth muscle relaxant properties. AB - N,O-Diacylated-N-hydroxyarylsulfonamides are capable of slowly releasing nitroxyl (HNO) by simple, non-enzymatic hydrolysis in Krebs solution at 37 degrees C. Release of nitric oxide (NO) was not seen. These compounds were also found to elicit vasorelaxation in rabbit thoracic aorta in vitro, presumably as a result of their ability to release HNO. This effect was enhanced by the addition of superoxide dismutase (SOD). Thus, these results are consistent with previous work indicating that HNO is a potent vasorelaxant. PMID- 1417813 TI - Tissue-specific response of estrogen receptor gene expression to estrogen in chick. AB - We have developed a sensitive assay system by RT (reverse transcription) PCR(polymerase chain reaction) to detect the low level of chicken estrogen receptor (cER) transcript. Using this system, the differential expression of cER gene in chick tissues was observed. Moreover, we found that the oviduct cER transcript levels in chick was not affected, albeit the remarkable growth of this tissue, by exogenous estrogen. In contrast, estrogen enhanced the hepatic cER transcript level several folds. Thus, the present study clearly showed a novel tissue-specific response of cER gene expression to estrogen in chick. PMID- 1417814 TI - A recombinant rat vascular AT1 receptor confers growth properties to angiotensin II in Chinese hamster ovary cells. AB - A rat vascular AT1 receptor cDNA has been stably expressed into Chinese Hamster Ovary cells and the resulting recombinant AT1a receptor has been functionally characterized. This receptor binds 125I Sar1-angiotensin II with an affinity of 0.9 nM and the displacement of this ligand by a series of peptidic and nonpeptidic analogs is shown. Binding of angiotensin II to this receptor causes a rapid increase in inositol phosphate production, whereas this effect is not observed in nontransfected cells. Des-aspartyl1 angiotensin II and at a lesser extent angiotensin I are also able to produce an increase in inositol phosphates. More importantly, the actions of angiotensin II on cell division were clearly demonstrated in this model, since angiotensin II is able to stimulate DNA synthesis by 400% and double the cell population of the transfected cells in 36 hours in the absence of any other growth factor, whereas no effect is observed in nontransfected cells. PMID- 1417815 TI - A single-stranded DNA binding protein which interacts with sequences within the bovine preprotachykinin promoter: regulation by nerve growth factor. AB - The production of substance P (SP) and the mRNA encoding its precursor preprotachykinin (PPT) is regulated by nerve growth factor (NGF) in dorsal root ganglion neurons. We have shown previously that two regions of the bovine PPT promoter are capable of mediating the induction by NGF of the downstream structural gene in transfected PC12 cells. Both regions contained a sequence element, similar to a known transcription factor binding site, which is present in several other NGF-regulated genes. We show here that PC12 cells contain a single-stranded DNA binding protein (SSBP-PC12) which can interact specifically with this site. Binding activity was increased by NGF treatment of PC12 cells. PMID- 1417816 TI - Tissue- and cell-specific control of guinea pig cathepsin E gene expression. AB - Northern blotting of RNAs from normal guinea pig tissues revealed that the tissue distribution of cathepsin E mRNA was relatively limited and the highest level of the mRNA was observed in the stomach mucosa. Expression of the mRNA was also observed in the spleen, although the level was very low. These results were in good agreement with the distribution of the cathepsin E-producing cells as revealed by immunohistochemistry. In the separated fractions of dispersed mucosal cells prepared from the stomach by centrifugal elutriation, the extent of cathepsin E mRNA expression was closely correlated with the enrichment of the producing cells. In addition, both CCGG and GCGC sites within the gene region were hypomethylated to a greater extent in the producing tissues than elsewhere, reflecting specific hypomethylation in the producing cells. The observed tissue- and cell-specific transcriptional control of cathepsin E gene, which is correlated with a decreased level of methylation in the gene region, suggests that the enzyme is probably involved in specific functions of particular differentiated cells, especially those of the stomach mucosa. PMID- 1417817 TI - Quinobene, a new potent anti-HIV agent. AB - A simple synthesis of the sulfonated azo dye Quinobene (3) and its derivatives, as well as the results of their evaluation in anti-HIV screening have been described. Thus, reacting the diazonium salt of 4,4'-diaminostilbene-2,2' disulfonic acid with 8-hydroxyquinoline-5-sulfonic acid yielded the readily isolable title compound. The lithium and tetramethylammonium salts of Quinobene and its complexes with Cu(II), Zn(II), Mg(II) were also prepared. In vitro tests showed considerable activity of these compounds against HIV-1. PMID- 1417818 TI - Identification of amino acid residues of rat angiotensin II receptor for ligand binding by site directed mutagenesis. AB - To determine the specific mechanism of ligand binding to angiotensin (Ang II) receptor AT1, mutagenized rat receptor cDNAs were expressed transiently in COS-7 cells and the effect of the mutations on the binding to peptidic and non-peptidic ligands was analyzed by Scatchard plots. Mutation of Lys199 to Gln in the intramembrane domain strongly reduced the affinity to both [125I] Ang II and [125I]-1Sar, 8Ile-Ang II whereas mutation of two other Lys had little effect, indicating involvement of Lys199 in binding ligands. Replacement of each of four Cys in the extracellular domain markedly reduced binding affinity, indicating the importance of two putative disulfide bridges in the formation of active receptor conformation. Substitution of Asp for Asn in N-glycosylation had no effect on ligand binding or expression of the receptor. These studies indicate mutated receptors are expressed in the plasma membrane and are amenable for further detailed studies. PMID- 1417819 TI - Molecular characterization and expression of the cell-associated glucosyltransferase gene from Streptococcus mutans. AB - A gene encoding cell-associated glucosyltransferase (CA-GTase) was cloned from Streptococcus mutans MT8148 into Escherichia coli DH5 alpha by using a low-copy number plasmid, pMW119. After screening of a gene library with the oligonucleotide probe designed on the basis of a partial amino acid sequence of CA-GTase, a recombinant plasmid, pSK6, that had a 5.6 kb insert carrying the CA GTase gene was selected. The gene product (recombinant CA-GTase) of pSK6 was expressed by using a lac promoter in pMW119. Western blotting revealed that rCA GTase reacted with antibody to CA-GTase. rCA-GTase was found to synthesize water insoluble glucans. Southern blotting indicated that the MT8148 chromosome contained another gene which was homologous to pSK6. A plasmid harboring this gene (pSK16) was also isolated from the gene library, the gene product of pSK16 exhibited GTase activity but ten times lower than that of pSK6. PMID- 1417820 TI - Oxidation-induced persistent activation of protein kinase C in hippocampal homogenates. AB - Incubation of purified protein kinase C with H2O2 results in the generation of a persistently activated form of the enzyme which is no longer dependent on Ca2+ or lipid cofactors. This oxidative activation of purified protein kinase C requires added Fe2+ in the incubation medium. Treatment of the soluble fraction of hippocampal homogenates with H2O2 also leads to persistent activation of protein kinase C; however, oxidative activation of protein kinase C under these conditions does not require the addition of Fe2+. The persistently activated form of protein kinase C appears as a novel peak of activity on DE52 anion exchange columns, suggesting a modification of the charge character of the enzyme. Thus, oxidative modification of protein kinase C can result in its persistent activation, and this mechanism may constitute a pathway for physiological activation of the enzyme in the hippocampus. PMID- 1417821 TI - A POU-domain gene of zebrafish, ZFPOU1, specifically expressed in the developing neural tissues. AB - We have isolated a POU domain-containing cDNA (ZFPOU1) from a cDNA library of zebrafish (Brachydanio rerio). The ZFPOU1 cDNA contained an open reading frame encoding a 425 amino acid peptide. The conserved POU domain was located near the carboxy terminus. The deduced amino acid sequence of the reading frame was most similar to that of the mouse class III POU-domain gene, Brain-1. Northern blot analysis revealed that the ZFPOU1 transcripts first appeared at the early neurula stage of embryogenesis and transiently increased thereafter. A significant level of expression, however, was not found in adult tissues except in the brain. In situ hybridization analysis demonstrated that the ZFPOU1 transcripts were localized in the neural tissues of embryos, but not in mesodermal, endodermal or ectodermal tissues. In adult zebrafish, the ZFPOU1 transcripts were detected in the restricted regions of the brain. Spatial and temporal expression patterns suggest that ZFPOU1 has distinct roles in the early neural development of zebrafish. PMID- 1417822 TI - Diacylglycerol formation from phosphatidylcholine in angiotensin II-stimulated vascular smooth muscle cells. AB - In cultured vascular smooth muscle cells (VSMC), angiotensin II (Ang II) induces a biphasic diacylglycerol (DAG) formation peaking at 15 sec and 5 min. Although it has been well established that the first peak is produced by the hydrolysis of inositol 4,5-bisphosphate (PIP2), the origin of the second DAG peak has never been examined in detail. In the present paper, we provide evidence that the second peak of DAG formation in Ang II-stimulated VSMC originates mainly from PC. PMID- 1417823 TI - Purification and characterization of a new 120 kDa alkaline proteinase of Trypanosoma cruzi. AB - A new alkaline proteinase activity was identified in cell-free extracts of Trypanosoma cruzi epimastigotes on the basis of its ability to hydrolyze the fluorogenic substrate N-Z-Gly-Gly-Arg-AMC. The optimal activity was at pH 8.0. After a three step-chromatography procedure using two anionic columns (DEAE Sepharose and Mono Q) and a chromatofocusing column (Mono P), the proteolytic activity was associated with a single 120 kDa protein and was called Tc 120 proteinase. The molecular mass of the proteinase was confirmed by direct visualization of the proteolytic activity using a fluorometric assay on SDS-PAGE. The Tc 120 proteinase which also cleaves N-Z-Arg-AMC, N-Z-Phe-Arg-AMC and N glutaryl-Gly-Arg-AMC substrates, is a cysteine-type proteinase with an unusual low sensitivity to E-64. PMID- 1417824 TI - Identification of calcitonin gene related peptide in ovine hypothalamic extract. AB - Calcitonin gene-related polypeptide (CGRP) was purified from ovine hypothalamic extracts. Its amino acid sequence was determined as: Ser-(Cys)-Asn-Thr-Ala-Thr (Cys)-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser- Arg-Ser - Gly-Gly-Val-Val-Lys-Ser Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Gln-Ala-Phe- NH2. This sequence differs from rat CGRP by two amino acid substitutions (Ser for Asp25 and Gln for Glu35). Adenylate cyclase stimulating activity in rat pituitary cell cultures was monitored during the isolation. CGRP had adenylate cyclase stimulating activity comparable to corticotropin-releasing hormone, suggesting a hypophysiotropic role for CGRP. This is the first chemical characterization of CGRP in the brain (hypothalamus). PMID- 1417825 TI - Adenosine modulates cell growth in human epidermoid carcinoma (A431) cells. AB - Adenosine mediates many physiological functions via activation of extracellular receptors. The modulation of cell growth by adenosine was found to be receptor mediated. In A431 cells adenosine evoked a biphasic response in which a low concentration (approximately 10 microM) produced inhibition of colony formation but at higher concentrations (up to 100 microM) this inhibition was progressively reversed. Evidence for the involvement of A1 (inhibitory) and A2 (stimulatory) adenosine receptors in regulating cell growth of these tumor cells was obtained through plating efficiency studies based on the relative potency of adenosine agonists and antagonists. When both A1 and A2 receptors were blocked, colony formation or growth was not inhibited at low concentrations of adenosine but was inhibited at high adenosine concentrations. PMID- 1417826 TI - Structure of the human spermidine/spermine N1-acetyltransferase gene (exon/intron gene organization and localization to Xp22.1). AB - The super induction of spermidine/spermine N1-acetyltransferase (SSAT), has been implicated in the cytotoxic response of human solid tumors to the bis(ethyl)polyamines. The SSAT response is a phenotype specific response and is modulated at the level of increased steady-state mRNA levels and enzyme protein. The human genomic region (4,095 bases) containing the coding sequence of SSAT has been cloned and localized to the Xp22.1 region. Primer extension analysis indicates the transcription of SSAT starts 179 bases upstream from the translational start site and appears to be under the control of a "TATA-less" promoter. The availability of this human clone will facilitate the direct functional examination of the SSAT gene. PMID- 1417827 TI - Neointima formation after vascular injury is angiotensin II mediated. AB - Smooth muscle proliferation of injured blood vessels leads to pathologically significant stenosis in animals and humans. We report here the pharmacological confirmation of an involvement of angiotensin II in this process as a major, necessary mediator of neointima formation. In the rat carotid artery, an animal model of post-angioplastic restenosis, we have obtained by local intraluminal infusion of peptidic angiotensin II antagonist after balloon catheterization, suppression of neointima formation and preservation of the luminal integrity. Sham operated control animals treated without medication and operated control animals treated simultaneously with angiotensin converting enzyme inhibitor and with agonistic angiotensin II, suffered major stenosis through the myoproliferative response of the injured vessel. These results prove that angiotensin II plays a key role as a mediator of vascular neointima formation. PMID- 1417828 TI - Activation of phospholipase C by the agonist U46619 is inhibited by cromakalim induced hyperpolarization in porcine coronary artery. AB - We measured inositol 1,4,5-trisphosphate (IP3) production, intracellular calcium concentration ([Ca2+]i) and force of contraction induced by a thromboxane A2 analogue U46619 in porcine coronary artery to elucidate the relaxant effect of a K+ channel opener cromakalim. Cromakalim (10 microM) significantly inhibited the production of IP3, Ca2+ release from intracellular stores and contraction induced by 300 nM U46619. The inhibitory effect of cromakalim on IP3 was blocked by a K+ channel blocker tetrabutylammonium (TBA, 3 mM) and counteracted by 20 mM KCl induced depolarization. These results suggest that the hyperpolarization of the plasma membrane by cromakalim inhibits the activation of phospholipase via the stimulation of the thromboxane A2 receptor to result in vasodilation. PMID- 1417829 TI - Synthesis of 6-substituted tetrazolo[1,5-c]pyrimidin-5(6H)ones: new modification of 3'-azido-3'-deoxythymidine. AB - An efficient method for the preparation of 6-methyltetrazolo-[1,5-c]pyrimidin 5(6H)ones using as the precursors 4-chloro-1,2-dihydro-1-methyl-2-oxopyrimidines is described. The method is also extended to the synthesis of novel tetrazole analogue of 3'-azido-3'-deoxythymidine (AZT). PMID- 1417830 TI - An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. AB - A mitochondrial DNA mutation at nucleotide position 14,484 was found in 14 independent probands with Leber hereditary optic neuropathy and in 0/250 controls. The 14,484 mutation, which changes methionine-64 to valine in a conserved domain of the ND-6 gene, occurred in association with a mitochondrial DNA haplotype that includes the 13,708 secondary mutation in 10/14 probands. An associated mutation at nucleotide position 3,394, which changes conserved tyrosine-30 to histidine in the ND-1 gene, was observed in 5/14 probands positive for the 14,484 mutation, all of whom harbored the same mitochondrial DNA haplotype. Multiple mitochondrial DNA mutations may interact in the pathogenesis of Leber hereditary optic neuropathy and the 13,708 secondary mutation appears to play a central role in this process. PMID- 1417832 TI - A novel fluorescent fatty acid, 5-methyl-BDY-3-dodecanoic acid, is a potential probe in lipid transport studies by incorporating selectively to lipid classes of BHK cells. AB - The 5-methyl-BDY-3-dodecanoic acid (B12FA) labelling of BHK cell lipids was analyzed by thin layer and reverse phase column chromatography. Incorporation to phospholipids was selective: over 90% of B12FA label was enriched in phosphatidylcholine. The major molecular species of PC was that containing palmitate as the unlabelled fatty acid. Small amounts of label was also found in other phosphoglycerides, but not in sphingomyelin. Triglycerides and diglycerides constituted the main B12FA-labelled neutral lipid classes; however, no label was found in cholesterol esters. B12FA was degraded to shorter homologues, which had significantly slower lipid incorporation rates. B12FA-labelled cells displayed in a microscope initially green reticular type fluorescence, but later red spherical structures, representing neutral lipid droplets, could also be seen. It is concluded that B12FA does not incorporate indiscriminately to all lipid classes of BHK cells, but is enriched to PC, diglycerides and triglycerides, which could be utilized in studies on lipid transport as well as metabolism. PMID- 1417831 TI - Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. AB - Vascular endothelial cell growth factor (VEGF), also known as vascular permeability factor, is an endothelial cell mitogen which stimulates angiogenesis. Here we report that a previously identified receptor tyrosine kinase gene, KDR, encodes a receptor for VEGF. Expression of KDR in CMT-3 (cells which do not contain receptors for VEGF) allows for saturable 125I-VEGF binding with high affinity (KD = 75 pM). Affinity cross-linking of 125I-VEGF to KDR transfected CMT-3 cells results in specific labeling of two proteins of M(r) = 195 and 235 kDa. The KDR receptor tyrosine kinase shares structural similarities with a recently reported receptor for VEGF, flt, in a manner reminiscent of the similarities between the alpha and beta forms of the PDGF receptors. PMID- 1417833 TI - DNA strand cleavage at 8-hydroxyguanine residues by hot piperidine treatment. AB - The two findings indicate that 8-hydroxyguanine(8-OH-Gua) is a hot piperidine sensitive lesion in DNA. These are cleavages of DNA containing 8-OH-Gua at the site of this residue and decomposition of 8-hydroxydeoxyguanosine when the DNA and nucleoside were treated in 1 M piperidine for 30 min at 90 degrees C. However, no cleavage was observed in DNA containing 8-hydroxyadenine or O6 methylguanine. 8-OH-Gua was found to be different from apurinic sites that are also alkali-labile lesions since the former was more resistant to alkali treatment. This property of 8-OH-Gua can be used as a check for the incorporation of this base into DNA after the synthesis of DNA containing 8-OH-Gua at a specific position or possibly can be one of the markers for the identification of 8-OH-Gua formed in DNA exposed to reactive oxygen species. PMID- 1417834 TI - Mouse hepatic microsomal oxidation of aliphatic aldehydes (C8 to C11) to carboxylic acids. AB - Addition of saturated and alpha, beta-unsaturated aliphatic aldehydes (C8 to C11) significantly increased NADPH oxidation with mouse hepatic microsomes, and the aldehydes themselves were oxidized to the corresponding carboxylic acids. When these aldehyde substrates were incubated similarly under oxygen-18 gas and the carboxylic acids formed were analyzed by GC-MS after methylation, it was indicated that oxygen-18 was significantly incorporated into the carboxylic acids formed from alpha, beta-unsaturated aldehydes, but not significantly into the carboxylic acids formed from saturated aldehydes. These results indicate that enzyme and/or mechanism responsible for the oxidation of these two types of aldehydes is different from each other. PMID- 1417835 TI - Differential regulation of putrescine uptake in Trypanosoma cruzi and other trypanosomatids. AB - Putrescine uptake in Trypanosoma cruzi epimastigotes is 10 to 50-fold higher than in Leishmania mexicana or Crithidia fasciculata. Polyamine transport in all these trypanosomatids is an energy-dependent process strongly inhibited by the presence of 2,4-dinitrophenol or KCN. Putrescine uptake in T. cruzi and L. mexicana was markedly decreased by the proton ionophore carbonylcyanide m chlorophenylhydrazone but it was not affected by ouabain, a Na(+)-K+ pump inhibitor. The depletion of intracellular polyamines by treatment of parasite cultures with alpha-difluoromethylornithine elicited a marked induction of putrescine uptake in L. mexicana and C. fasciculata by increasing considerably the Vmax of this process. Conversely, the uptake of putrescine in T. cruzi was essentially unchanged by the same treatment. The differential regulation of putrescine transport in T. cruzi might be related to some distinctive features of polyamine metabolism in this parasite. PMID- 1417836 TI - Identification of heptanal and nonanal in bronchoalveolar lavage from rats exposed to low levels of ozone. AB - Heptanal and nonanal are identified from in vitro studies as potential biomarkers of exposure to ozone, the former resulting from ozonation of palmitoleic acid and the latter from oleic acid. An analytical method is developed based on derivatization using O-pentafluorobenzylhydroxylamine HCl and gas chromatography. These molecules also are present in the lung lavage of Sprague-Dawley rats exposed to 1.3 ppm ozone for 10 hr. These results suggest aldehydes may be useful dosimeters for ozone and indicate that unsaturated fatty acids in the lung lining fluid layer undergo ozonation in vivo. PMID- 1417838 TI - Direct evidence for protein kinase C involvement in insulin-stimulated hexose uptake. AB - Insulin has been reported to translocate protein kinase C (PKC) in rat adipocytes, and activation of PKC by phorbol esters is known to increase hexose uptake in these cells (1.2). To test the hypothesis that PKC may participate in insulin-stimulated hexose uptake, adipocytes were partially depleted of protein kinase C by overnight phorbol ester treatment, thereby impairing insulin effects on hexose uptake. Purified PKC was then introduced into these PKC-depleted adipocytes by electropermeabilization, and this fully restored insulin-stimulated hexose uptake. These findings provide direct evidence that PKC is required for insulin-stimulated hexose uptake. PMID- 1417837 TI - Hormonal and nutritional stimuli modulate apolipoprotein B mRNA editing in mouse liver. AB - Human livers produce apoB-100, a major protein of VLDL, while intestines produce apoB-48, the major protein of chylomicrons. ApoB-48 is translated from apoB-100 mRNAs that are post-transcriptionally edited at codon 2153, converting CAA (glutamine) to TAA, a stop codon. In contrast to humans, mouse and rat livers contain the apoB-100 mRNA editing mechanism. Because hormones and nutrients affect the metabolism of apoB containing lipoproteins, we studied the effects of sex hormones and diets on apoB mRNA editing. Groups of male and female C3H/HeJ mice were castrated and treated with 17 beta-estradiol at 0.16 (E2L) or at 5 micrograms (E2H), or with testosterone propionate at 1 microgram/g body weight/day for 14 days. Plasma apoB levels and ratios of apoB-100/apoB-48 both increased 2-fold, but only in the E2H group. To determine if the increased apoB 100/apoB-48 ratios were associated with altered levels of apoB-100 and apoB-48 mRNA, both forms of apoB mRNA were quantified. We found that indeed ApoB-100 mRNA increased 1.8-fold (p < 0.025) compared to apoB-48 mRNA only in the E2H group. Next, we studied the individual effects of dietary fatty acids and dietary cholesterol on the relative abundance of apoB-100 and apoB-48 mRNA. Contrary to the estrogen effect, the high fat-combination diet increased apoB-48 mRNA relative to apoB-100 mRNA. Total plasma apoB as well as apoB-48 synthesis in liver also increased. Our studies demonstrate that estrogens and high fat diet both modulate apoB editing in mouse liver, but that estrogens and fat diet affected apoB mRNA editing in opposite directions. PMID- 1417840 TI - A new synthetic hypoglycaemic polysaccharide. AB - The synthetic (1-->6)-alpha-D-glucopyranan with branching and without branching were tested as a new hypoglycaemic drug. (1-->6)-alpha-D-glucopyranan having an alpha-D-glucopyranosyl branch at the C-3 position (1) showed a remarkable hypoglycaemic activity on i.p. injection to mice. The polysaccharide having both alpha- and beta-glucopyranosyl branches (2) also lowered the blood sugar (glucose) level in mice. On the other hand, the synthetic linear (1-->6)-alpha-D glucopyranan (3) and alpha-D-glucopyranosyl branched polysaccharide (4) did not have a hypoglycaemic function, indicating that the branching glucose units are essential for the biological activity. PMID- 1417839 TI - Distribution of GLUT3 glucose transporter protein in human tissues. AB - To investigate the tissue distribution of the GLUT3 glucose transporter isoform in human tissue we produced affinity purified antibodies to the COOH terminus of the human GLUT3. Both antibodies recognize a specific GLUT3 band in oocytes injected with GLUT3 mRNA but not in those injected with H2O or GLUT1, 2, 4, 5 mRNA. This immunoreactive band in GLUT3 injected oocytes is photolabelled by cytochalasin-B in the presence of L- but not D-glucose indicating that it is a glucose transporter. A high cross reactivity between the human GLUT3 antibodies and a 43 kDa cytoskeletal actin band was identified in all oocyte lysates and many human tissues. However, the specific GLUT3 band could be distinguished from the actin band by carbonate treatment which preferentially solubilized the actin band. Using these antibodies we show that GLUT3 is present as a 45-48 kDa protein in human brain with lower levels detectable in heart, placenta, liver and a barely detectable level in kidney. No GLUT3 was detected in membranes from any of 3 skeletal muscle groups investigated. We conclude that a major role of GLUT3 in humans is as the brain neuronal glucose transporter. PMID- 1417841 TI - Presence of nuclear factors bound to both cAMP-responsive element and AP1 factor binding site in the porcine anterior pituitary. AB - Factors binding to consensus sequences of the cAMP-responsive element (CRE) and the AP1 factor binding site (AP1) were investigated using porcine anterior pituitary nuclear extracts. Each element showed specific gel mobility shifts. By reciprocal competition for the AP1 and CRE binding, CRE prevented AP1 binding completely. On the other hand, AP1 decreased the CRE binding considerably to 20%, suggesting that approximately 80% of the total CRE binding is due to factors which bind to a common site shared by both CRE and AP1, whereas proteins binding to AP1 alone are absent. Relative binding affinities of AP1 against CRE estimated from the reciprocal competition data were 0.17 for CRE binding and 0.56 for AP1 binding. UV cross-linking experiments showed that CRE and AP1 gave different patterns consisting of different molecular size. Inconsistency of the relative binding affinities and the multiple molecular size of binding factors, cannot be explained simply by the presence of two types of binding factor, common CRE/AP1 binding and specific CRE-binding factors. A more likely explanation is that the CRE/AP1-binding factors alter the dimer form by changing each respective partner to bind CRE and/or AP1. PMID- 1417842 TI - The adenovirus E3 region 14.7 kDa protein, heat and sodium arsenite inhibit the TNF-induced release of arachidonic acid. AB - In this report we show that the adenovirus E3 region 14.7 kDa protein, heat and sodium arsenite, which have been defined previously as inhibitors of cytolysis, inhibit the tumor necrosis factor-alpha (TNF)-induced release of 3H-arachidonic acid from cycloheximide-sensitized C3HA fibroblasts. Since the A23187-induced release of 3H-a.a. was unaffected, our results suggest that these inhibitors provide resistance to lysis by selectively interfering with the lytic response pathway. Our results also show that heat and sodium arsenite can themselves induce the release of 3H-arachidonic acid. These results raise the possibility that stressor-induced resistance to TNF results from the selective desensitization of phospholipase A2. PMID- 1417843 TI - High reactivity of aortic fibroblasts to vasoactive agents: endothelins, bradykinin and nucleotides. AB - Cultured aortic fibroblasts express high affinity Et-1 binding sites that poorly discriminate between Et-1 and Et-3. Both endothelins activate phospholipase C hence indicating the presence of ETB receptors. Fibroblasts respond to bradykinin by large activations of phospholipase C and increases in [Ca2+]i in a manner that was abolished by D-Arg, [Hyp3,Thi5,8,D-Phe7]-bradykinin, thus indicating the presence of B2 kinin receptors. Finally, ATP, UTP and ADP increases [Ca2+]i in aortic fibroblasts via a nucleotide receptor that has a higher affinity for ATP and UTP (3 microM) than for ADP (50 microM) and that is distinct from P2x and P2y purinoceptors. PMID- 1417844 TI - High pressure induced inactivation of ferrous cytochrome P-450 LM2 (IIB4) CO complex: evidence for the presence of two conformers in the oligomer. AB - The effect of high pressure on the spectral properties of cytochrome P-450 LM2(Fe2+)-CO complex was studied. The application of high pressure was shown to induce the conversion of cytochrome P-450 to P-420. In the solution when P-450 was oligomeric only about 65% of the total converted to P-420. The remaining portion of cytochrome P-450 was stable at pressures up to 6 kbar. When P-450 was incorporated into membranes or when it was succinylated, the proportion of the pressure sensitive fraction was slightly higher (about 75%). Dissociation of P 450 oligomers into monomers was made by addition of 0.2% Triton N-101. Monomers were the most sensitive to pressure; they could be completely converted to P-420. These results have been interpreted as evidence for the existence of two different conformers of P-450 LM2, which differ in pressure stability. Splitting between these two states appears to be a result of the oligomeric organization of cytochrome P-450 in solution and in the membrane. PMID- 1417846 TI - Casein kinase-2 structure-function relationship: creation of a set of mutants of the beta subunit that variably surrogate the wildtype beta subunit function. AB - Nine mutants of human casein kinase-2 beta subunit have been created and assayed for their ability to assemble with the catalytic alpha subunit to give, at a 1:1 molar ratio, a fully competent CK-2 holoenzyme as judged by the following criteria: 1) the generation of an active heterotetrameric form of CK-2 exhibiting the expected sedimentation coefficient and 2) the enhancement of catalytic activity of CK-2 alpha. Extended deletions of 71 and 44 residues from the C terminal end, but not a 7 residue deletion (including the cdc2 phosphorylation site) prevent both reconstitution of the holoenzyme and, consequently, stimulation of activity. This indicates that residue(s) located in the 171-209 sequence is essential for reconstitution. Also a four residue's N-terminal deletion (removing the autophosphorylation site) and single to quintuple substitutions of alanine for the acidic residues clustered in the 55-70 sequence give rise to mutants that still assemble with the alpha subunit to give a tetrameric holoenzyme. However, in the case of the mutants A57,59, A63,64, A59 61,63,64 in vitro assembly with the CK-2 alpha subunit was not complete. There were also intermediate complexes, free alpha-subunit and beta-mutants found to sediment at various positions in the sucrose density gradient. In comparison to CK-2 beta +, mutants A57,59, A59-61 and A59-61,63,64 show an increased stimulation of the catalytic activity supporting the view that these residues play a crucial role in determining the basal activity of reconstituted CK-2 holoenzyme. PMID- 1417845 TI - Tyr-179 and Lys-183 are essential for enzymatic activity of 11 beta hydroxysteroid dehydrogenase. AB - Tyr-179 and Lys-183 are likely to be functionally important residues in 11 beta hydroxysteroid dehydrogenase, as these amino acids are absolutely conserved in all members of the "short chain dehydrogenase" family. We modified these residues by site-directed mutagenesis of rat cDNA and transfected these constructs into CHO cells. A highly but not absolutely conserved residue, Asp-110, was also studied. Mutation of Tyr-179 to Phe or Ser completely abolished enzymatic activity (interconversion of corticosterone and 11-dehydrocorticosterone), as did Lys-183-->Arg. Asp-110-->Asn affected activity only mildly. Tyr-179 and Lys-183 may be directly involved in the catalytic function of this class of enzymes. PMID- 1417847 TI - Iodothyronine 5-deiodinase in rat posterior pituitary. AB - We first describe the presence of iodothyronine 5-deiodinase (5D) in the neural lobe of rat pituitary. 6-n-Propyl-2-thiouracil (PTU), a specific inhibitor of type-I deiodinase, had no effect, showing that 5D in neurohypophysis is of type III isozyme, which is specific for 5-deiodination and has been found only in the brain, placenta and skin. The presence of 5D (type-III) together with our previous report of 5'-deiodinase (type-I in euthyroidism and type-II in hypothyroidism) shows that the isozymes of deiodinases in the neurohypophysis are quite similar to those in the brain. These data suggest a previously unrecognized role of thyroid hormone in posterior pituitary physiology. PMID- 1417848 TI - Anchored anti-HLA class I monoclonal antibody fails to induce inhibition of PHA activated lymphocytes proliferation. AB - It is known that anti-HLA Class I antibodies inhibit the proliferative response of PHA-activated T-lymphocytes. We found that plastic- or sepharose-linked anti HLA Class I monoclonal antibody 01.65 does not inhibit either [3H]Thymidine incorporation or recruitment in the cell cycle, nor does it reduce the expression of c-myc mRNA and the membrane expression of Interleukin-2 Receptor and Transferrin Receptor. Furthermore, particulate Protein Kinase C is not affected by anchored anti-HLA Class I monoclonal antibody 01.65. We suggest that anti-HLA Class I monoclonal antibody may act through crosslinking or internalization of HLA Class I antigens. PMID- 1417849 TI - Endothelin-1 stimulates its own synthesis in human endothelial cells. AB - We studied whether endothelin-1 (ET-1) would affect its own synthesis. Human umbilical cord vein endothelial cells in methionine-poor culture medium containing [35S] methionine were treated with synthetic ET-1 or ET-3. Immunoprecipitation of 35 S-labeled ET-1 was performed with rabbit ET-1 antiserum. ET-1 caused an 40 +/- 4% (mean +/- SEM) increase of immunoprecipitable 35 S-labeled ET-1 as confirmed by its elution point in reversed phase high power liquid chromatography (HPLC). ET-3 caused a 23 +/- 2% increase in ET-1 concentration. Amplification of cDNA by PCR showed both ET-1 and ETB receptor mRNAs in human cord vein endothelial cells. We conclude that ET-1 increases its own synthesis in endothelial cells. This suggests a positive autocrine feed-back action of ET-1 on its own synthesis, an effect which is probably mediated by non specific ETB receptors. PMID- 1417850 TI - Differential regulation of rat AT1a and AT1b receptor mRNA. AB - Rat type 1 angiotensin II receptor has two subtypes, namely type 1a and type 1b. The regulation of the expressions of these two subtype receptor mRNAs was studied by using a competitive polymerase chain reaction method. The expression of the type 1a mRNA in the liver was negatively and that of the type 1b mRNA in the adrenal was positively modulated by bilateral nephrectomy. In the ventricle of 16 week old Spontaneously hypertensive rat, the expression level of the AT1b receptor mRNA was higher than that in the ventricle of the age-matched Wistar Kyoto rat, while the expression levels of the AT1a mRNA in the ventricle were almost similar between the two strains at this age. Although type 1a and type 1b have almost similar functional properties, the expressions of their mRNAs were differentially regulated. PMID- 1417851 TI - Tumor necrosis factor and interleukin-1 induce activin A gene expression in a human bone marrow stromal cell line. AB - Activin A, a homodimer of the beta A chain, regulates hematopoiesis. In a human bone marrow-derived stromal cell line, KM-102, phorbol myristate acetate, tumor necrosis factor-alpha and interleukin-1 beta induced great increases in beta A chain mRNA levels and production of activin A activities. The phorbol ester induced beta A chain gene expression was inhibited by cycloheximide and down regulation of protein kinase C, whereas the cytokine-induced expression was little affected by these treatments. These results indicate that the inflammatory cytokines directly stimulate beta A chain gene expression via protein kinase C independent pathways. PMID- 1417852 TI - A vasopressor factor partially purified from human parathyroid glands. AB - Recently, a parathyroid hypertensive factor was postulated to play a role in the pathogenesis of hypertension in genetically hypertensive rats. Therefore it was examined, whether in human parathyroid glands a vasopressor substance can be detected. For this purpose, homogenates of hyperplastic parathyroid glands from 20 patients with tertiary hyperparathyroidism were deproteinized and fractionated by gel chromatography. The fractions obtained were tested for vasopressor activity in isolated perfused rat kidneys. A vasopressor fraction containing substances of 0.6-2.5 kDa was identified in the parathyroid glands. The responsible product was heat sensitive, peptidase-, trypsin- and carboxypeptidase y- sensitive and hydrophilic, as it did not bind to hydrophobic reversed-phase gel. These results suggest that parathyroid glands contain a hydrophilic peptide like vasopressor substance different from the parathyroid hormone. PMID- 1417853 TI - Insulin inhibits norepinephrine overflow from peripheral sympathetic nerve ending. AB - The effects of insulin on peripheral nervous system are unknown. We therefore studied the effects of insulin on sympathetic nerve activity in isolated mesenteric arteries of Sprague-Dawley rats. The overflow of norepinephrine (NE) by electrical stimulation was used as the index of sympathetic nervous system activity. Insulin (0.5 to 1U/l) decreased the NE release in a dose-dependent fashion. This inhibitory effect was, however, reversed by either 5 x 10(-5)M cocaine or 5 x 10(-4)M ouabain treatment. Thus, we postulate that insulin attenuates NE overflow from peripheral sympathetic nerve endings, probably due to enhanced NE reuptake. PMID- 1417854 TI - cDNA cloning of rat LRP, a receptor like protein tyrosine phosphatase, and evidence for its gene regulation in cultured rat mesangial cells. AB - Protein tyrosine phosphatases (PTPases) are a family of enzymes that play a crucial role in the regulation of signal transduction mediated by reversible protein tyrosine phosphorylation. To understand the significance of PTPases in physiological and pathophysiological processes in the kidney, we isolated three cDNA segments encoding PTPases (LAR, LRP and a novel PTPase) from rat kidney by polymerase chain reaction (PCR). Using PCR product as a probe, we isolated a full length cDNA of rat LRP. LRP cDNA encoded a single membrane spanning protein consisted of 796 amino acids, with two tandemly located intracellular PTPase domains. By Northern analysis, a ubiquitous pattern of LRP gene expression in rat tissues was demonstrated. In cultured rat mesangial cells, LRP mRNA was detected and the mRNA level was suppressed by either interleukin-1 or interleukin-6 treatment. PMID- 1417855 TI - Effect of sphingoid bases on basal and insulin-stimulated 2-deoxyglucose transport in skeletal muscle. AB - Incubation of rat soleus muscles with 50 microM sphingosine or 50 microM sphinganine augmented basal 2-deoxy-D-glucose (2DG) transport 32%, but reduced the response to 0.1 and 1.0 mU insulin/ml by 17 and 27%, respectively. When the muscles were incubated with 50 microM phytosphingosine, a 63-93% increase in basal 2DG transport was observed. However, this treatment had no effect on insulin-stimulated 2DG transport. The phytosphingosine-induced increase in basal 2-DG transport was inhibited 93 and 98% with 35 and 70 microM cytochalasin B, respectively, suggesting that it is mediated by glucose transporters. Cellular accumulation of L-glucose, which is not mediated by glucose transporters, was not affected by phytosphingosine. It is concluded that (a) both sphingosine and sphinganine increase basal 2DG transport in muscle but diminish insulin stimulated transport, and (b) phytosphingosine stimulates basal 2DG transport in muscle by a mechanism involving glucose transporters. PMID- 1417856 TI - Organotin-flavone complexes: a new class of fluorescent probes for F1F0ATPase. AB - Fluorescent 5-coordinate organotin-flavone complexes of 3-hydroxy-flavone (Hof) and 3,5,7,2',4',-pentahydroxyflavone (morin) are good inhibitors of mitochondrial F1F0ATPase but do not inhibit F1-ATPase and they have been examined as possible fluorescent probes of F1F0ATPase. R2SnX (morin) complexes exhibit low fluorescence enhancement on binding to mitochondrial membranes with no displacement by equimolar tributyltin. In contrast R2SnX (of) complexes exhibit high fluorescence enhancement whose extent is variable and is displacable by equimolar tributyltin. Fluorescence enhancement by R2SnX (of) complexes correlates with the ATPase I50 values. Dialkyltin-3-hydroxy flavone, R2SnX(of), complexes act as a new class of fluorescent probes which titrate the F0 segment of F1F0ATPase. PMID- 1417857 TI - Deficiency of 8-hydroxyguanine DNA endonuclease activity and accumulation of the 8-hydroxyguanine in mutator mutant (mutM) of Escherichia coli. AB - In this report, we have characterized mutM mutant with respect to its ability to repair 8-hydroxyguanine (oh8Gua) in DNA. The oh8Gua DNA endonuclease activity in mutM strain was minimal as compared with that in the wild-type cells. The presence of oh8Gua in DNA of mutM was 6-fold that of the wild-type strain corresponding to a characteristically higher frequency of G.C-->T.A transversions in this mutant strain. These results suggest that mutator phenotype of mutM is at least partially due to a spontaneous accumulation of oh8Gua resulting from a greatly reduced oh8Gua DNA endonuclease activity. PMID- 1417858 TI - Novel missense mutation in cardiac beta myosin heavy chain gene found in a Japanese patient with hypertrophic cardiomyopathy. AB - We have analyzed the exon 9, 13, 14, 15, and 16 of cardiac beta myosin heavy chain gene in 96 Japanese patients with hypertrophic cardiomyopathy by using PCR DNA conformation polymorphism analysis. The analysis revealed a sequence variation of the exon 16 in one patient. The sequence variation of a G to C transversion with replacement of Asn by Lys at the codon 615 was confirmed by sequencing and by dot-blot hybridization with an allele-specific oligonucleotide probe. Because the missense mutation was found at the residue conserved through birds to humans, this mutation was suggested to be a cause of hypertrophic cardiomyopathy in the patient. This is the first report of a mutant cardiac beta myosin heavy chain gene in the Japanese population. PMID- 1417859 TI - The synthesis of cadystins, heavy metal chelating peptides, is induced in the fission yeast by wounds of the cell wall or by incubation with chitosan. AB - It has been shown that heavy metal administration induced the synthesis of cadystins, the small metal chelating peptide with the general structure of (gamma glu-cys)n-gly, in the fission yeast and in plants. Besides heavy metals, wounds to the cell surface or the incubation with chitosan induced the cadystin synthesis in the fission yeast. Under these induction conditions, the membrane permeability of the fission yeast significantly increased suggesting the structural alteration of the membrane. In these induction, the synthesized cadystins formed complexes with the cellular zinc ions together with or without glutathione. PMID- 1417860 TI - Cloning of a major heparan sulfate proteoglycan from brain and identification as the rat form of glypican. AB - We have obtained the complete coding sequence of a highly conserved heparan sulfate proteoglycan which we previously characterized biochemically after isolation from rat brain. An open reading frame of 558 amino acids encodes a protein with a molecular mass of 62 kDa containing three peptide sequences present in the isolated proteoglycan. The total sequence obtained is 3.5 kb long, including 1.6 kb of 3'-untranslated sequence and 0.2 kb of 5'-untranslated sequence. The deduced amino acid sequence and the 3'- and 5'-untranslated sequences have 89% and 66-80% identity, respectively, with those of a phosphatidylinositol-anchored human lung fibroblast heparan sulfate proteoglycan (glypican) for which mRNA is detectable in a large number of human cell lines. Our data therefore demonstrate that this major heparan sulfate proteoglycan of brain is the rat form of glypican. PMID- 1417861 TI - Mutations at the putative junction sites of the yeast VMA1 protein, the catalytic subunit of the vacuolar membrane H(+)-ATPase, inhibit its processing by protein splicing. AB - A single gene, VMA1, encodes the 69-kDa subunit of the vacuolar membrane H(+) ATPase in the yeast Saccharomyces cerevisiae. We have proposed that the subunit is synthesized as a precursor of 120 kDa (1,071 amino acids) and then converted to the 69-kDa form by an unusual processing reaction, which removes the internal domain of 454 amino acids (residues 284-737) and joins the N- and C-terminal domains. Cysteine to serine mutations at residues 284 and 738, the residues that bracket the internal domain, were introduced into the VMA1 gene by site-directed mutagenesis, and the mutant genes were expressed in a null vma1 mutant. Cells harboring either of the mutant vma1 genes accumulate nonfunctional fragments of the subunit. The mutation of Cys-284 inhibited the cleavage of the N-terminal junction site. Cys-738-->Ser mutation appeared to block the processing at both junction sites although the mutant gene yielded a small fraction of the functional 69-kDa subunit. PMID- 1417862 TI - Presence and turnover of adenosine diphosphate ribose in human erythrocytes. AB - ADP-ribose was detected in human red blood cells (RBC) at 0.45 +/- 0.1 microM concentrations. These levels could be estimated after purification of ADP-ribose by means of three sequential HPLC fractionations of RBC extracts. Extraction was performed by sonication of RBC either in trichloroacetic acid, followed by centrifugation, or in carbonate-bicarbonate buffer, pH 10.0, followed by rapid ultrafiltration. Neither procedure of extraction caused artefactual formation of ADP-ribose. Prolonged incubation of intact RBC in isotonic buffer containing labeled orthophosphate resulted in the slow incorporation of radioactivity into ADP-ribose. Identification of the labeled ADP-ribose was confirmed upon incubation of the purified metabolite with nucleotide pyrophosphatase, yielding radioactive 5'-AMP and ribose 5-phosphate, while its exposure to a nonspecific deaminase resulted in the quantitative formation of labeled inosine diphosphate ribose. PMID- 1417863 TI - Preliminary characterization of a nuclear factor interacting with the silencer element at the 3'-side of the chicken alpha-globin gene domain. AB - A silencer element has been identified previously on the 3'-side of the chicken alpha-globin genes placed next to the major enhancer in this domain (Recillas Targa et al., unpublished). Deletion fragments of this negative element show the requirement of the entire DNA segment for maximum silencing activity. Additionally, the sub-fragments including the previously defined SF1 (Silencer Factor 1) sequence seem to play an important role on the negative action of this silencer. Preliminary characterization of the nuclear factor interacting with the SF1 sequence was carried out. Methylation interference experiments show the contact points and, by electrophoretic retardation analysis with SF1 and SF1 mutated oligonucleotides, the critical role of these contacts points on the formation of the DNA-protein complex could be demonstrated. These results provide a basis for further experiments on the characterization and understanding of the mechanisms of action of the coupled positive and negative regulatory elements. PMID- 1417864 TI - Characterization of cysteine residues of glutathione S-transferase P: evidence for steric hindrance of substrate binding by a bulky adduct to cysteine 47. AB - Glutathione S-transferase P (GST-P) lost the enzymatic activity by 7-fluoro-4 sulfamoyl-2, 1, 3-benzodiazole (ABD-F), a thiol-group chemical modifier, but did not by methylmethanethiol-sulfonate. Both ABD-F and methylmethanethiolsulfonate reacted with Cys47 and Cys101. These two cysteine residues were site-directedly mutated with serine residues. Only the Cys101Ser lost the enzymatic activity by the treatment of ABD-F. On carbon 13 NMR experiments, a NMR signal of S-[13C]CH3 adduct to Cys47 did not show any change by the addition of S-hexylglutathione. These facts revealed that Cys47 did not locate at the active site, and a bulky adduct to Cys47 hindered the binding of substrates to the active site. PMID- 1417865 TI - An S1 nuclease-sensitive homopurine/homopyrimidine domain in the PDGF A-chain promoter contains a novel binding site for the growth factor-inducible protein EGR-1. AB - Transcription of the platelet-derived growth factor (PDGF) A-chain gene is activated in cells exposed to growth factors. We now have identified a homopurine/homopyrimidine domain in the promoter region of the PDGF A-chain gene that exhibits S1 nuclease sensitivity in vitro and that contains a novel binding site (5'-TCCTCCTCCTCCTC-3') for the growth factor inducible transcription factor EGR-1 as demonstrated in gel mobility shift assays. Sequences similar to this novel EGR-1 binding site were observed also in five growth-related genes and shown to bind to EGR-1 in competition assays, suggesting that EGR-1 may influence the transcriptional regulation of these growth-related genes. PMID- 1417866 TI - Localization of an adipocyte-specific retinoic acid response domain controlling S14 gene transcription. AB - S14 gene transcription is induced by retinoic acid (RA) in cultured adipocytes, but not preadipocytes. Transfection of 3T3-L1 cells with S14-CAT fusion genes showed that adipocyte-specific RA responsive cis-acting elements are located between -1588 and -1381 bp upstream from the 5' end of the S14 gene. This region has enhancer-like properties. In contrast, an artificial RA response element conferred RA control to a CAT gene in both preadipocyte and adipocyte phenotypes indicating that the RA regulatory network is functional in both phenotypes. These studies show that RA receptors interact with adipocyte-specific transcription factors to control S14 gene expression. PMID- 1417867 TI - The interplay between basicity, conformation, and enzymatic reduction in biliverdins. AB - Biliverdins with extended conformations are reduced by biliverdin reductase (BvR) at higher rates than biliverdins with helical conformations. To find out the molecular basis for this important feature of BvR mechanism, helical and extended biliverdins were titrated for their acid-base equilibria in a protic solvent (methanol). It was found that the basicity of biliverdins increases with the stretching of the conformation. Biliverdin IX gamma (all-syn) has a pKa = 3.6; 5,10,15-syn,syn,anti-biliverdin has a pKa = 3.7; 5,10,15-syn,anti,syn-biliverdin has a pKa = 6.1; 5,10,15-syn,anti,anti-biliverdin has a pKa = 6.4; and 5,10,15 all-anti-biliverdin has a pKa = 7.9. The increase in basicity with progressive stretching of conformations closely parallels the increase in the reduction rates by BvR. A biliverdin constrained by a four carbon chain to a helical conformation and which is a very weak base (pKa = 0.4) is not reduced by BvR. Nucleophilic additions of 2-mercaptoethanol at the C10 in biliverdins closely parallel their basicities, as can be expected if the formation of a positive mesomeric species at C10 is linked to the basicity (i.e., the ease of protonation) of the N23 on the pyrrolenine ring. PMID- 1417868 TI - Structure and chromosomal location of the human granulin gene. AB - Granulins are a family of cysteine rich polypeptides some of which have growth modulatory activity. We showed previously that the granulins are encoded within the same precursor consisting of seven granulin domains arranged in tandem. Here we report the chromosomal location and structural organization of the protein coding region of the granulin gene. The granulin gene was assigned to chromosome 17 using DNA from human-hamster somatic cell hybrids. The protein-coding region of the granulin gene was shown to comprise 12 exons covering about 3700 bp. Each tandem granulin repeat is encoded by two non-equivalent exons, a configuration unique to the granulins that would permit the formation of hybrid granulin-like proteins by alternate splicing. PMID- 1417869 TI - Further evidence of the SA gene as a candidate gene contributing to the hypertension in spontaneously hypertensive rat. AB - We have recently reported that the allele of the SA gene of the Spontaneously hypertensive rat (SHR) has a capacity to influence blood pressure in a F2 rat population prepared from SHR and Wistar-Kyoto rat. In the present study, we have undertaken a similar genetic co-segregation analysis of the F2 rat population prepared from SHR and Lewis rat. The result indicated that, although overall effects of the SA gene genotypes on blood pressure were not significant, a correlation of the genotypes of the SA gene with blood pressure was significantly observed in the female rats of this population. The present results further strengthen our hypothesis that the SA gene, or a gene closely linked to this gene, has a capacity to influence blood pressure. PMID- 1417870 TI - Effect of a mechanical tension on the hydration of DNA in fibres. AB - Fiber X-ray diffraction and measurement of fibre dimensions yield information about the effects of a mechanical tension on hydration of DNA in fibres. At a given relative humidity, the mechanical tension changes the DNA conformation but does not modify the number of water molecules associated to a nucleotide. The number of water molecules per nucleotide necessary to maintain B form decreases for increasing tensions applied to the DNA fibre. Form transitions can be opposed by mechanical tensions; an energy of 1 Kcal per mole of nucleotide pairs is sufficient to prevent the B to A transition. PMID- 1417871 TI - Expression and possible function of glucose transporter protein GLUT1 during preimplantation mouse development from oocytes to blastocysts. AB - A micro-Western analysis method both sensitive and quantitative enough to analyze oocytes and embryos is developed. GLUT1 protein is present in mouse oocytes and preimplantation embryos and levels are increased by fertilization and with time in ensuing embryonic development; the levels were 20-fold greater in blastocysts than in unfertilized oocytes. Similar increases were observed in glucose uptake by oocytes and embryos, suggesting that they may depend on GLUT1 expression. These results suggest that GLUT1 expression may explain a switch in substrate preference of the embryo from pyruvate to glucose during preimplantation development. PMID- 1417872 TI - Binding of myosin subfragment-1 to F-actin. AB - During a part of the hydrolytic cycle, myosin head (S1) carries no nucleotide and binds strongly to an actin filament forming a rigor bond. At saturating concentration of S1 in rigor, S1 is well known to form 1:1 complex with actin. However, we have provided evidence that under certain conditions S1 could also form a complex with 2 actin monomers in a filament (Andreev, O.A. & Borejdo, J. (1991) Biochem. Biophys. Res. Comm. 177, 350-356). This view was recently challenged by Carlier & Didry (Carlier, M-F. & Didry, D. (1992) Biochem. Biophys. Res. Comm. 183, 970-974) who interpreted our data by suggesting that F-actin underwent a simple depolymerization and implied that, when only actin in the F form was scored, the real stoichiometry in our experiments was 1:1. We show here that under conditions of our experiments less than 8% of actin was depolymerized. Moreover, we have repeated the experiments in the presence of phalloidin and show that under these conditions too, when S1 was added slowly to a fixed concentration of F-actin, it formed a different complex with F-actin than when it was added quickly. This confirms our original conclusion that S1 can bind actin in two different ways and shows that depolymerization of F-actin is not responsible for this finding. PMID- 1417873 TI - Fibronectin stimulates protein synthesis in cultured fibroblastic cells. AB - Protein synthesis in mouse embryo fibroblastic (NIH-L1) cells was stimulated by addition of fibronectin (FN) to the culture medium as a soluble factor. This stimulatory activity of FN appeared only when the cells were cultured over their saturated density. A hexapeptide (GRGDSP) containing the RGDS cell attachment site of FN could not prevent the stimulation of protein synthesis. Moreover, activity of the stimulatory FN was not affected by inclusion of cytochalasin B, which is known to release FN from cell surface by disorganizing actin cytoarchitecture. These results suggest that the signaling of change in protein synthesis rate by FN may be distinct from signaling involving cell attachment and spreading. PMID- 1417874 TI - Monomer-dimer equilibrium of nitroso-aromatic spin trap 3,5-dibromo-4 nitrosobenzenesulfonic acid, sodium salt (DBNBS), in aqueous solution. AB - 3,5-Dibromo-4-nitrosobenzenesulfonic acid, sodium salt (DBNBS), which is widely used as a spin trap in biological systems, was allowed to form the monomer-dimer equilibrium in aqueous solution, and its equilibrium constant (Kc) was determined by NMR measurement and visible spectrum analysis. The Kc values obtained from the two different methods were virtually identical and evaluated as 1.3 x 10(-3) mol dm-3 at 25 degrees C. Further, the molar extinction coefficient of DBNBS monomer (epsilon 760) was determined to be 34 dm3mol-1cm-1. The present results indicate that only a minor portion (ca. 20%) of dissolved DBNBS (10 mmol dm-3) is practically capable of spin trapping under the conditions most widely used in biological studies. PMID- 1417875 TI - Fatty acid binding protein inhibits glycolithocholate sulfation. AB - Sulfation of hepatotoxic monohydroxy bile salts is viewed as an important detoxification mechanism. Bile salts are bound by fatty acid binding protein (FABP) with decreasing affinity as the extent of their hydroxylation increases. This binding has the potential to interfere with sulfation of monohydroxy bile salts and to augment their toxicity. FABP inhibits monohydroxy bile salt sulfation via bile salt sulfotransferases BST 1 and 2. With BST 1, the main BST, we obtained a maximal reduction of sulfation by 42.8 +/- 8.1%, using 10 microM glycolithocholate as substrate. FABP had no effect on sulfation of either 10 microM glycodeoxycholate or glycochenodeoxycholate. FABP may therefore specifically alter hepatotoxicity of lithocholate and its metabolites. PMID- 1417876 TI - Isolation and characterization of riboflavin carrier protein from human amniotic fluid. AB - A specific protein exhibiting immunological cross-reactivity with chicken riboflavin carrier protein has been purified to homogeneity from human amniotic fluid by use of ion-exchange and affinity chromatography. The protein is similar to its avian counterpart in terms of molecular size, distribution of 125I labelled tryptic peptides during finger printing, and preferential binding to riboflavin. Immunologically, they are homologous since most of the monoclonal antibodies raised against the avian protein cross-react with the purified human vitamin carrier. PMID- 1417877 TI - Superoxide dismutase and glutathione peroxidase activities in rat pineal gland. AB - Activities of the antioxidant enzymes superoxide dismutase (E.C.1.15.1.1) and glutathione peroxidase (E.C.1.11.1.9) were measured in the pineal gland of adult rats. For comparative purpose superoxide dismutase was also measured in the anterior hypothalamic area (suprachiasmatic region) and the liver and glutathione peroxidase in the liver. The mean activities obtained for superoxide dismutase were: pineal (103.13 +/- 4.70 N.U.), anterior hypothalamus (132.88 +/- 4.73 N.U.), liver (253.91 +/- 0.10 N.U.) and, for glutathione peroxidase were: pineal (0.027 +/- 0.005 I.U.) and liver (0.103 +/- 0.031 I.U.). It was shown for the first time that superoxide dismutase and glutathione peroxidase are present in pineal gland being part of its antioxidant defense system. PMID- 1417878 TI - Fusion of phospholipid vesicles induced by phospholipase D in the presence of calcium ion. AB - Fusion of phospholipid vesicles composed of various combination of phosphatidylcholine, phosphatidylethanolamine and phosphatidic acid was induced by Ca2+ in the presence or absence of phospholipase D from Streptomyces chromofuscus. For the vesicles composed of 20:50:30 molar ratio of phosphatidylcholine/phosphatidylethanolamine/phosphatidic acid, the initial fusion rate was much faster than the expected value when only the conversion of phosphatidylcholine and phosphatidylethanolamine into phosphatidic acid by phospholipase D is taken into account. These observations are discussed in terms of the involvement of outer monolayer of the vesicles and the enzyme activity itself in the fusion process. PMID- 1417879 TI - Interaction of Artocarpus lectins with human IgA does not involve asparagine linked oligosaccharide of the immunoglobulin. AB - In view of the controversy with respect to the interaction of jacalin with human IgA2, a study was undertaken to assess the reactivity of the Artocarpus heterophyllus lectin, as well as the lectin from Artocarpus integer (lectin C), with subclasses of human immunoglobulin A by ELISA. Our data is consistent with the view that Artocarpus lectins have no affinity for the IgA2 immunoglobulins. In further support of the findings, we have established that N-linked oligosaccharide moieties of IgA have no significant bearing in the lectin immunoglobulin binding. Interaction was also not affected in the presence of 1% (w/v) BSA. PMID- 1417880 TI - Oxalate production from glyoxylate by lactate dehydrogenase in vitro: inhibition by reduced glutathione, cysteine, cysteamine. AB - Lactate dehydrogenase is known to act as a dismutase converting glyoxylate to oxalate and glycolate. LDH (sources: human erythrocytes, human plasma; rabbit muscle; rat liver) activity was assayed at 340 nm using glyoxylate (5.0 mmol/l) and NADH. The LDH activity (approx. % of control) in all the cases decreased respectively in the presence of 5.0 and 10.0 mmol/l of cysteine (45 and 20), cysteamine (45 and 20), and GSH (55 and 30). This decrease in LDH activity resulted in decreased oxalate production from glyoxylate (0.5 mmol/l). A 50% inhibition in oxalate production was observed in presence of 0.3 mmol/l cysteine, 0.35 mmol/l cysteamine, and 2.0 mmol/l GSH. The results suggest that the net LDH activity towards oxalate production may be regulated by the free SH-groups in the cell. This possibility needs evaluation as a tool to lower endogenous oxalate production and the associated risk of stone formation. PMID- 1417881 TI - Chemical modification of arginine residues of protein kinase C. AB - Modification of basic residues of protein kinase C by phenylglyoxal results in a reversible, dose-dependent inhibition of autophosphorylation and substrate phosphorylation. The inhibition is not due to specific modification of the Ca2+ or ATP binding sites. Modified PKC bound more [3H] phorbol ester than unmodified providing further evidence that the binding of lipids and the catalytic phosphotransferase activity have different regulatory sequences. Additionally, the effects of these modifying reagents were different on enzyme stimulated by phorbol esters or by the endogenous activator, 1,2-diacylglycerol. These studies suggest that there is at least 1 arginine residue that is unique in the binding site of these different activators. PMID- 1417882 TI - Destruction of vitamin K1 of cultured carrot cells by ultraviolet radiation and its effect on plasma membrane electron transport reactions. AB - The effect of ultraviolet radiation on plasma membrane electron transport reactions was studied in cultured carrot cells. It was found that a 90 min treatment inhibited transmembrane hexacyanoferrate reduction greater than 50%. Extraction of lipophilic quinones from irradiated cells showed that vitamin K1 and coenzyme Q were totally destroyed, while control unirradiated cells showed the presence of 0.4 mumole vitamin K1 g dry wt.-1. The addition of exogenous vitamin K1 in concentrations of 1-10 microM partially restored plasma membrane electron transport with impermeable hexacyanoferrate as the electron acceptor. Total restoration of activity was given by growing irradiated cells in vitamin K1 supplemented growth media for 6 days. This shows that vitamin K1 may function as a member of the transplasma membrane electron transport chain in cultured carrot cells. PMID- 1417883 TI - Detection of human satellite II DNA-binding polypeptides in HeLa cellular and nuclear extracts. AB - Highly-repetitive satellite DNA's are generally located in centromeric heterochromatin, yet little is known about how they are maintained and condensed. In an effort to address this question, we have searched for specific satellite DNA-binding proteins in cell-free extracts (both total cellular and nuclear), prepared from HeLa cells, using southwestern blotting. Four polypeptides were detected that specifically bound to a human 1797 bp EcoRI satellite II DNA, which consists in large part of tandemly repeated pentamer (5' TTCCA 3') units, but not to a control probe from plasmid pBR322. These proteins have apparent molecular weights of 100, 93, 77 and 34 kDa and were termed satellite binding protein (Sbp) -1, -2, -3, and -4, respectively. PMID- 1417884 TI - Putrescine uptake by rabbit intestinal brush-border membrane vesicles. AB - The transport of putrescine in rabbit intestinal brush-border membrane vesicles is a time-dependent, Na+ and H+ gradient-independent slow process, reaching a high equilibrium level from 1 hr onwards. An approximately 12-fold concentration gradient of 5.4 microM putrescine was generated in the vesicles after 3 h of incubation at 25 degrees C, suggesting a substantial binding of the polyamine to membrane components. Putrescine uptake did not appear to occur via a polyamine-H+ exchange pathway, but the activity of transport was strongly reduced when the medium pH was lowered from 7.5 to 6.0. Although it was inhibited in the presence of SCN-, putrescine uptake was found neither to involve a preferred anion nor to be sensitive to changes in the membrane potential. Putrescine accumulation was substantially stimulated in the presence of a 10 mM concentration of the divalent cations Ca2+, Mg2+ or Ba2+, unlike the monovalent cations K+, Na+ or Li+. Despite the presence of a Ca(2+)-dependent transglutaminase activity, vesicular accumulation does not appear to result from covalent binding of putrescine to membrane peptides. Inhibition of the uptake by polyamines, unlike choline and dibasic amino acids, shows that putrescine may bind noncovalently to other specific anionic sites. PMID- 1417885 TI - Evaluation of protein assay methods for pollen and fungal spore extracts. AB - The usual procedures available for protein estimation of biological extracts often give variable results due to presence of many peptides and coloured materials. To identify a suitable method for allergenic extracts, protein was estimated from common pollen and fungal antigens by modified Lowry's (ML), Bradford (B), micro-Kjeldahl (MK), Bicinchoninic acid (BCA) and modified BCA (MBCA) assays. Bradford assay resulted in low protein values, whereas BCA method gave very high values in general. Statistical analysis of the results revealed similarity between protein values quantitated by MK, ML and MBCA methods for most of the extracts. Graded volumes of the extracts on subjecting to protein estimation by these three methods showed linear response, while recovery of a protein (bovine serum albumin) added to the extracts was greater than 90%. PMID- 1417886 TI - Validation of the MTT dye assay for enumeration of cells in proliferative and antiproliferative assays. AB - Increasing use is being made of colorimetric assays to quantitate viable cells, e.g., the cellular reduction of the tetrazolium salt, MTT, to formazan by mitochondrial succinate dehydrogenase. We validated this assay for cell proliferation in mixed lymphocyte cultures as compared with 3H-thymidine uptake, and for inhibition of cell proliferation induced by interferon with results compared by direct cell counting. We also found that cells do not, as previously assumed, require functional mitochondria: there were no differences in formazan production by normal cells or respiratory defective cells in which mitochondria had been poisoned by the nucleic acid toxin, ethidium bromide. The high reproducibility of MTT metabolism by lymphoblasts and various cultured cell lines establishes the reliability and versatility of this method for quantitating cell numbers. PMID- 1417887 TI - Stimulation of the protein synthesis by fibronectin is specific for untransformed fibroblastic cells. AB - In the preceding paper, we showed that fibronectin (FN) in solution has the ability to stimulate protein synthesis in NIH-L1 fibroblastic cells. We show here that FN stimulated protein synthesis also in other normal fibroblast cell lines, WI-38 and BALB/3T3, but did so only slightly in their transformed cell lines, L1 4NQOH10, WI-38 VA-13 and KN(7)8; and in rat hepatocytes in primary culture and rat liver epidermoid cells (GR-1) it hardly affected the synthesis. Augmentation of the protein synthesis rate was not attributable to stimulation of collagen synthesis. This stimulatory activity of FN was enhanced remarkably by proteolytic digestion of FN with trypsin. PMID- 1417888 TI - Active site mapping studies of malate dehydrogenase : identification of essential amino acid residues by o-phthalaldehyde. AB - Mitochondrial malate dehydrogenase (MDH) was found to be rapidly inactivated by o phthalaldehyde. MDH-o-phthalaldehyde adduct gives a characteristic absorption maximum at 337 nm. Moreover, this derivative shows fluorescence emission maxima at 405 nm when excited at 337 nm and 280 nm. These results were consistent with isoindole ring formation in which the -SH group of cysteine and epsilon-NH2 group of lysine participate in the reaction. The enzyme was found to be protected against o-phthalaldehyde inactivation by NADH, indicating that the essential residues are present at or near the coenzyme binding site. Stoichiometric results indicate that 4 isoindole derivatives are formed per enzyme molecule upon complete inactivation. However, 90% of the activity loss was accompanied by the formation of 2 moles of isoindole per mole of the enzyme. These approaches give consistent evidence that two cysteines along with two lysines in close proximity are essential for the enzymatic activity. PMID- 1417890 TI - Comparative study of the effect of ethanol on the fluidity of subcellular hepatic membranes. AB - The aim of this study has been to compare the effects of chronic ethanol administration on the lipid composition and fluidity of chick-liver microsomes and mitochondria. Cholesterol levels were increased only in microsomal membranes whilst the fatty-acid profiles were considerably altered in the major phospholipids in both membranes. By using fluorescence polarization we found that ethanol produces a disorganisation of acyl chains in the core of microsomes and mitochondria and consequently causes higher fluidity. In addition, opposite changes were induced by ethanol in the polar region of the microsomes, inducing a more rigid area in the membrane. PMID- 1417889 TI - Synthesis and characterization of some collagen sequence analogs. AB - Some analogs of natural collagen sequences (773-779) were synthesized. The peptides were hydrolyzed at the Gly-Ile bond not only by crude collagenase isolated from normal rat liver, but also by the bacterial Clostridium histolyticum collagenase. The reason for this unusual cleavage site in the latter case may lie in the unordered secondary structure of the substrates measured by CD spectroscopy. PMID- 1417891 TI - A novel fluorescent pH indicator for the acidic range. AB - Reaction of a commercial preparation of lissamine-rhodamine B sulfonyl chloride with primary amines gives rise to two sulfonamide derivatives, of which one behaves as a pH indicator with maximal fluorescence emission in the acidic range and a pKa of about 4.6. The structure of this derivative and the mechanism of fluorescence dependence on pH, elucidated by means of NMR, is presented. PMID- 1417892 TI - A study of the carboxyl groups of sheep brain tubulin. AB - Tubulin was isolated from whole sheep brain by ammonium sulphate fractionation followed by ion exchange chromatography using DEAE-Sephadex in 10 mM sodium phosphate buffer pH 7.0. It was essentially free from contaminating proteins as shown by SDS-PAGE electrophoresis and was active by the criterion of colchicine binding. Hydrogen ion titration of the sheep brain tubulin was performed under native conditions. In the present study, only that pH range has been selected for analysis where carboxyl groups (most of which are located in the C-terminal regions of both the alpha- and beta- subunits) deprotonate. The results indicated the presence of 75 carboxyl groups per dimer upto pH 5.5. Of these, 46 titrated with a pK of 3.7 and the remaining 29 with a pK of 3.5. PMID- 1417893 TI - Biochemical, cytogenetic, and morphological characteristics of human primary and metastatic prostate cancer cell lines. AB - Metastatic properties of human prostatic cancer cell lines (ND-1 and DU-145) were examined using various biochemical techniques. DU-145 cells had a higher metastatic potential than ND-1 cells. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with considerable structural rearrangement. ND-1 cells had a modal chromosome number range lower than DU-145 cells (45-66, compared to 54-62). Ploidy analysis revealed that DU-145 cells showed hyperdiploidy with a greater amount of proliferation than the majority of ND-1 cells. Electron microscopic studies revealed little change in the cell morphology of either line. DU-145 cells had lower phosphatidyl choline levels and higher sphingomyelin levels than ND-1. DU-145 cells had much lower arachidonic acid levels than ND-1 cells. SDS-polyacrylamide gel electrophoresis revealed protein differences between the two cell lines. This study demonstrates for the first time that lipids, proteins and cytogenetic parameters differ in human primary and secondary prostate cancer cell lines. PMID- 1417894 TI - Immunospecificity and affinity studies on anti-luteinizing hormone releasing hormone antibodies developed by azo-LHRH-TT and azo-LHRH-BSA conjugates. AB - Monoclonal and conventional antibodies against the 'self' decapeptide LHRH produced by azo-LHRH-TT and azo-LHRH-BSA conjugates were studied for immunoreactivity with native LHRH, azo-LHRH, LHRH (OH) and its fragments of sequence 1-10, 7-10, 4-10 and 4-6. The CoAb reacted 8-20% to azo-LHRH, 2-6% to LHRH-Lys, 1-3% LHRH-LYS-MDP and 0.5-1.68% to LHRH-Ala-Ala-Tuftsin but failed to react to LHRH free acid and its fragments. On the other hand MoAb reacted 4-6% to azo-LHRH and 10-18% to LHRH-Lys, 3-5% to LHRH-Ala-Ala-Tuftsin. These results indicate that the azotization drastically inhibited immunoreactivity but that the azo-LHRH-carrier conjugate preserved the immunogenic epitope responsible for the induction of an effective anti-LHRH antibody response. PMID- 1417895 TI - OmpT proteolysis of E. coli initiation factor IF2. Elimination of a cleavage site by site-directed mutagenesis. AB - A serious problem during purification of the E. coli initiation factor IF2 is a significant loss of native IF2 due to partial degradation. We have previously shown that the major fragment, IF2 gamma (65 kDa), is the result of cleavage of IF2 alpha at the peptide bond between lysine 289 and arginine 290. In this paper we demonstrate that the cleavage is a result of proteolysis by outer membrane protease OmpT occurring immediately after cell lysis and in the S30 supernatant. By protein engineering we have constructed an IF2 mutant Lys289-greater than Met and shown that the IF2 gamma cleavage site in this mutant protein is insensitive to cleavage by OmpT. However the mutant protein is cleaved by OmpT between arginine 279 and alanine 280, which is a novel sequence specificity for this protease. PMID- 1417896 TI - Changes in proteolytic activity during the growth of Trypanosoma cruzi epimastigotes. AB - The proteolytic pattern of Trypanosoma cruzi epimastigotes was studied using electrophoresis in gelatin containing SDS polyacrylamide gels. Under conditions that represent a nutritional stress such as the depletion of glucose in an axenic medium the results obtained showed a significant increase in the activity of two proteases of M(r) = 50,000 and M(r) = 60,000 as well as the appearance of higher molecular weight bands during the transition from log to stationary phase parasites. The use of different protease inhibitors strongly suggests that all these proteases are of the cysteine type, and their acid pH optimal would be in agreement with the possible localization in the parasite lysosomes. The reincubation of stationary phase parasites in fresh LIT medium or the addition of 0.4% glucose partially reverted the proteolytic pattern to that observed in log phase parasites. The regulation in the activity of these enzymes could be related to the well established use of amino acids for catabolic purpose after depletion of the medium glucose. PMID- 1417897 TI - Evaluation of sialic acid in lipoprotein fractions in fibrosarcoma bearing rats by 14C-glucose chase. AB - The changes in sialoglycoconjugates synthesis after administration of 14C-glucose to fibrosarcoma bearing rats were studied. After 1 hr treatment 14C-glucose tumor bearing rat synthesized hexosamine which contained more radioactivity when compared to sialic acid. On fractionation of lipoproteins, low density lipoproteins (LDL) contained more sialic acid. This was further confirmed by separating the lipoproteins, as more radioactivity incorporation was observed in the LDL fraction. It is noteworthy that inspite of the tumor, high density lipoproteins (HDL) did not show any change. PMID- 1417898 TI - Comparison of 2,5,5-trimethyl-1-pyrroline-N-oxide (M3PO) and 3,3,5,5-tetramethyl 1-pyrroline-N-oxide (M4PO) with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as spin traps. AB - 2,5,5-Trimethyl-1-pyrroline-N-oxide (M3PO) and 3,3,5,5-tetramethyl-1-pyrroline-N oxide (M4PO) were examined for their potential as spin traps used in biological samples, and the results obtained for M3PO and M4PO were compared with those of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) reported previously. The rate constants for the reactions of M3PO and M4PO with hydroxyl radicals were in the same order of that constant of DMPO. The hyperfine splitting constants of M4PO spin adducts were as informative as those of DMPO adducts. In the presence of ferric ions, M3PO and M4PO formed 2-hydroxy-2,5,5-dimethyl-1-pyrrolidinyloxy (M3PO-OH) and 2 hydroxy-3,3,5,5-tetramethyl-1-pyrrolidinyloxyl (M4PO-OH), respectively, by the nucleophilic addition of a water molecule, as we have already reported for DMPO. M4PO-OH was subjected to oxidation by ferric ions with a rate much slower than that for DMPO-OH, while M3PO-OH was not. The results indicate that M4PO is a spin trap suitable for biological applications and that nitrones having a methyl group at C2 represent improved spin traps. PMID- 1417899 TI - Changes in cholinesterase system in different brain areas during the development of behavioral tolerance to monocrotophos toxicity in male albino rats. AB - During the development of behavioral tolerance to the organophosphate monocrotophos, the activities of AChE and BuChE and the content of ACh were affected in different brain areas of male albino rats. The inhibition of AChE and BuChE activities and the elevation of ACh content were progressive till 7 days and were followed by a recovery trend towards normalcy. The changes correlated with the appearance and disappearance of signs and symptoms of toxicity, which were mainly cholinergic. The results suggest the possibility of de novo synthesis of cholinesterases resulting in the development of behavioral tolerance, as was evident by the recovery trend. The shift of toxicity from greater AChE inhibition during initial periods to greater BuChE inhibition during later periods indicates the possible involvement of pseudocholinesterases in the development of tolerance and in the reduction of toxicity. The brain areas were differentially affected. Cerebral cortex was more affected initially but it was the striatum that was affected more during later dosings. The results show that behavioral tolerance to monocrotophos toxicity develops despite changes in AChE and BuChE activities and ACh content. PMID- 1417900 TI - Identification of the number of genes encoding rat liver glutathione S transferase Yc, and their close location on the genome. AB - We have tried to determine the number of genes for the rat liver glutathione S transferase Yc, using specific probes prepared by polymerase chain reaction. DNA blot hybridization with specific probes and analysis in isolated genomic clones indicated that two copies of the Yc gene exist on the rat genome. Furthermore, DNA blot hybridization after clamped homogenous electric field gel electrophoresis indicated that the two copies of Yc gene family are closely located on the genome. PMID- 1417901 TI - New trypsin inhibitors are present in the coelomic fluid of the earthworm Lumbricus terrestris. AB - Proteinase-inhibiting components of the coelomic fluid of the earthworm Lumbricus terrestris were examined. Inhibition of proteinases of serine, aspartate and thiol families was tested. Very strong inhibition was observed only in the case of trypsin. Additional data suggest that the inhibition is related to proteins of molar mass of 42 kDa and 20 kDa, respectively. These two proteins are present in the coelomic fluid in several forms which differ in their isoelectric points. PMID- 1417902 TI - Effect of Helicobacter pylori lipopolysaccharide on the synthesis of sulfated gastric mucin. AB - The effect of H. pylori lipopolysaccharide on the synthesis and secretion of sulfated mucus glycoprotein in gastric mucosa was investigated. The lipopolysaccharide, while showing no discernible effect on the apomucin synthesis, exerted a profound inhibitory effect on the process of mucus glycoprotein glycosylation and sulfation, and evoked a rapid (within 15 min) inhibition (65%) in both mucin glycosylation and sulfation at its optimal concentration of 100 micrograms/ml. The data on mucin secretory responses indicated that the added lipopolysaccharide caused a 57% stimulation in sulfated mucin secretion within 15 min followed thereafter by inhibition, which reached a maximum of 32% by 45 min. The high molecular weight mucin form predominated in the initial secretion, while prolonged exposure to the lipopolysaccharide caused a significant increase in the low molecular weight mucin form. The results suggest that H. pylori lipopolysaccharide exerts detrimental effect on mucus glycoprotein sulfation and assembly. PMID- 1417903 TI - Actin binding to cross-linked 10 S smooth muscle myosin and 9 S heavy meromyosin. AB - Unphosphorylated gizzard myosin and heavy meromyosin were cross linked in the 10 S and 9 S states, respectively, by the cleavable cross linker, 3,3'-dithiobis (sulfosuccinimidyl-propionate) (DTSSP). The 10 S to 6 S transition for cross linked 10 S myosin appeared to cease; myosin appeared to remain in the 10 S state from measurements of viscosity and Mg(2+)-ATPase activity. The loss of the transition for cross-linked 9 S heavy meromyosin (HMM) was also indicated by Mg(2+)-ATPase activity. The cross links were cleaved by incubation with 50 mM dithiothreitol. From direct binding measurements, the estimated Kd's of actin to cross-linked and control heavy meromyosin were 167 and 16 microM, respectively. The binding affinity of cross-linked HMM to actin was restored to the control level by dithiothreitol. PMID- 1417904 TI - Adenosine metabolism in small coronary arteries of pig. AB - Adenosine preferentially relaxes small coronary arteries over large ones, and small bovine coronary arteries are also known to have a higher density of adenosine receptors. Here we report a possible role of adenosine metabolism in this process. Subcellular fractions, from right coronary artery (lumen diameter of 2-3 mm) of pig designated as large coronary artery and its subsequent branches (lumen diameter of 0.5-1 mm) as small coronary arteries, were prepared and characterized. In comparison to the various large artery subcellular fractions, the corresponding small artery fractions were richer in 5'-nucleotidase but poorer in adenosine deaminase. Thus a cascade of events may promote adenosine relaxation in small coronary arteries: higher activity of 5'-nucleotidase leads to production of more adenosine, larger number of receptors allows greater reactivity to adenosine, and lower adenosine deaminase level promotes prolonged action of adenosine. PMID- 1417905 TI - Ponceau S as a dye for quantitative protein assay. Its use in the presence of Triton X-100. AB - A Ponceau S reagent with high stability and slight response to pH changes, presence of organic solvents and detergents was prepared. Under these conditions, the reagent was tested to be suitable to quantify, in one-step procedure, different standard proteins. Moreover, this method offers the possibility to measure the protein content in the presence of the detergent Triton X-100. PMID- 1417906 TI - Crosslinking analysis of an endothelin receptor protein from human placenta. AB - Crosslinking of [125I]ET-1 to human placental membrane preparations in the absence of divalent cations revealed a [125I]ET-1.ET-1-receptor complex of 49 kDa and of 205 kDa on SDS-PAGE. In the presence of 20 mM MnCl2, however, only a complex of 205 kDa was observed. About 64% of the radioactively labeled receptor.ligand complex could be solubilised by digitonin and CHAPS. Size exclusion chromatography of the solubilised placental membranes, prelabeled with [125I]ET-1 in the presence of MnCl2, revealed two binding proteins of 200 and 33 kDa. In the absence of MnCl2, however, only a binding protein of 50 kDa was observed. Binding of [125I]ET-1 to the 200 kDa and 50 kDa but not to the 33 kDa protein was suppressed by unlabeled ET-1. Moreover the ET-1-receptor density in placental membranes (Bmax) increased significantly in the presence of MnCl2, whereas the dissociation constant (Kd) decreased. Thus, divalent cations exhibit marked and possibly physiologically important effects on molecular mass, Bmax and Kd of the [125I]ET-1.ET-1-receptor complex. The potential mechanism of action of Mn2+ ions on the ET-1-receptor is discussed. PMID- 1417907 TI - Effect of E. coli ribosomal protein S1 on the fidelity of the translational elongation step: reading and misreading of poly(U) and poly(dT). AB - Ribosomal protein S1 was selectively removed from E. coli ribosomes by affinity chromatography and the effect of added S1 on the translation of poly(dT) [which is read as poly(U) in the presence of neomycin] and on the misreading of poly(U) and poly(dT) were examined. S1 enhances the translation of poly(dT) at low template concentration, which is similar to the effect of S1 on poly(U) translation. The misreading of poly(dT) by E. coli ribosomes is at a lower level than is the case with poly(U). This low misreading is the same for "S1-dependent" and "S1-independent" modes of translation. On the other hand, the misreading of poly(U) is significantly reduced when S1 is present. These results thus indicate that S1 not only facilitates the binding of mRNA to the ribosome as already known, but also plays a role in the correct codon-dependent selection of aminoacyl-tRNA. PMID- 1417909 TI - Evaluation of the predicted secondary structure of bacteriorhodopsin. Prediction of the bovine rhodopsin secondary structure and its sequence similarity with bacteriorhodopsin. AB - The secondary structure of bacteriorhodopsin (bacR) is predicted using the Chou and Fasman method in conjunction with the hydropathic index of Kyte and Doolittle. The predicted bacR structure was compared with the structure determined by Henderson et al. (1990) using electron diffraction and was found to correlate extremely well. The secondary structure of bovine rhodopsin (bovR) was then predicted using the same techniques. The proposed transmembrane regions of bovR were then examined and found to have sequence similarity with those transmembrane regions of bacR. PMID- 1417908 TI - Concentrations and ratios of immunoreactive big-endothelin-1 and endothelin-1 in human, rat and rabbit plasma. AB - We have developed a radioimmunoassay for big-endothelin-1, based on a new antiserum recognizing human big-endothelin(1-38). On a molar base the antibody showed virtually no cross-reactivity with endothelin-1, -2, -3 (less than 0.001%), 14% cross-reactivity with the C-terminal big-endothelin(22-38) and only 0.85% cross-reactivity with porcine big-endothelin(1-39). However, immunoreactive big-endothelin-1 could be detected in human, rat and rabbit plasma. Thus, big endothelin-1 in rats and rabbits seem to be structurally similar to human big endothelin-1. Immunoreactive endothelin-1 was measured using a commercially available anti-endothelin-1 antibody. The measured concentrations of immunoreactive endothelin-1 and big-endothelin-1 and their molar ratios differed significantly in the three species. PMID- 1417910 TI - Lifetime determination of low sample concentrations: a new cuvette for highly accurate and sensitive fluorescence measurements. AB - A new cuvette was developed for spectrofluorometric measurements which increases the efficiency of recorded fluorescence emission by at least two-fold, decreasing, at the same time, the noise component of the record. It is suited for both steady-state and dynamic fluorescence measurements. Comparative data for both the classical and the novel cuvettes are presented here. PMID- 1417912 TI - Calcium ionophore A-23187 inhibits the secretion of beta-hexosaminidase from the GG2EE mouse macrophage cell line. AB - Secretion of the lysosomal enzyme beta-N-acetylhexosaminidase is inhibited by calcium ionophore A-23187 in the GG2EE macrophage cell line. Such inhibition is time and dose dependent. Calcium ionophore A-23187 treatment causes a change in the pattern of hexosaminidase isoenzymes detectable in the cell extract, as assessed by DEAE-cellulose chromatography. In particular, control cells show two hexosaminidase isoenzymes corresponding to hexosaminidase A and B, whereas cells treated with calcium ionophore A-23187 express a third isoenzyme form with properties similar to hexosaminidase S. PMID- 1417911 TI - Effects of insulin and a tumour promoter, TPA, on glucose transport and metabolism in retinal pigmented epithelium in vitro. AB - We have studied the effects of insulin, adenosine and 12-O-tetradecanoylphorbol 13-acetate (TPA) on glucose metabolism of the retinal pigmented epithelial (RPE) cells in vitro. Insulin stimulates glucose transport, glucose oxidation and lipogenesis in RPE cells. TPA at low concentrations of insulin increases the rates of glucose transport and glucose oxidation. Depletion of adenosine in RPE cells by adenosine deaminase increases the rate of both glucose transport and 14CO2 formation and improves insulin-sensitivity of both processes. The effects of TPA on RPE cells cannot be explained by the activation of protein kinase C. An alternative possibility is that the effects of TPA on insulin-stimulated glucose disposal in RPE cells is mediated by a change in adenosine concentration and/or the affinity/number of its receptors. PMID- 1417913 TI - Effect of insulin and thyroxine on catalase, glutathione-s-transferase, GSH and GSSG in alloxan diabetic rat red cells. AB - The levels of catalase (CAT), glutathione-s-transferase (GST), reduced glutathione (GSH) and oxidised glutathione (GSSG) were measured in red blood cells from control (C) and diabetic rats (D). Diabetes was induced by alloxan administration and diabetic rats were treated with insulin (D+I) and thyroxine (D+T4). On the third day of insulin withdrawal the CAT activity increased significantly. The GST activity showed an increase in D and D+I for one week, thyroxine treatment to D rats resulted in maintaining the GST activity at control levels. The levels of GSH and GSSG increased in D red cells after one week of insulin withdrawal but later, the GSH level was below the control level while the GSSG was at its control level. Insulin treatment to D rats did not reverse GSH level to control initially but controlled it at a later stage. Thyroxine, though, reversed GSH levels but enhanced GSSG in D rat red cells. PMID- 1417914 TI - Effect of lead on lipid peroxidation of the hepatic subcellular organelles of developing chick embryos. AB - The effect of lead on hepatic mitochondria and microsomes of chick embryo was studied with special attention to the role of lipid peroxidation in the manifestation of lead toxicity. Mitochondrial enzymes such as succinate dehydrogenase, cytochrome C oxidase and ATPase were found to decrease in a dose dependent manner upon lead administration. Further, mitochondrial cytochromes, microsomal cytochrome P-450 and heme levels were reduced considerably with concomitant increase of mitochondrial and microsomal lipid peroxides. In the present investigation an attempt has been made to correlate the lead induced lipid peroxidation, the loss of mitochondrial and microsomal hemoproteins and the inhibition of mitochondrial enzymes in chick embryo. PMID- 1417915 TI - Catecholamines are required for testosterone induction of ornithine decarboxylase in the mouse kidney. AB - This report presents a study on the influence of the adrenergic system on androgen-regulated ornithine decarboxylase activity (ODC) in the mouse kidney. We have found that the existing levels of renal ODC in male mice and the increase induced by testosterone in male, female, castrated male and hypophysectomized mice were dramatically impaired by catecholamine depletion produced by treatment with either alpha-methyl-p-tyrosine or reserpine. Blockade of beta-receptors by treatment of the animals with the antagonists propranolol or bisoprolol was unable to prevent the effect of testosterone on the renal enzyme. However, alpha i-blockade obtained by treatment with prazosin or phenoxybenzamine was partially effective to produce the decrease of basal ODC in control male or to diminish ODC induction produced by androgens. All these findings demonstrate that catecholamines and alpha 1-adrenergic receptors are implicated in androgen regulated ODC activity in the mouse kidney and suggest a plausible role of sympathetic renal innervation in enzyme induction by steroid hormones in this organ. PMID- 1417916 TI - D-xylose fermentation and catabolism in Fusarium oxysporum. AB - Fusarium oxysporum exhibits different fermentative capacities when grown under different aeration conditions. Highest ethanol and acetic acid yield coefficients were obtained under semi-aerobic culture conditions. Effect of aerobiosis on the levels of key enzymes and intracellular intermediary metabolites of pentose phosphate pathway, tricarboxylic acid cycle and glycolysis exhibited striking correlation with the fermentative character of metabolism. The results are discussed in relation to the energy levels in the cell, the redox balance and mitochondrial function. PMID- 1417917 TI - Androgenic status in cyclic and postmenopausal women: a comparison between smokers and nonsmokers. AB - Serum total testosterone (T), free testosterone (fT) sex hormone binding globulin (SHBG), androstenedione (A) and 3 alpha androstanediol glucuronide (3 alpha-diol G) levels as well as serum free androgen index (FAI), fT/T and 3 alpha-diol G/T ratios were measured in premenopausal and cyclic women, grouped according to sexual status and smoking status. Our results showed that serum T, fT, SHBG, A and 3 alpha-diol G levels were lower in cyclic women in the follicular than in the luteal phase of the ovarian cycle, although the differences between these values were not significant. Postmenopausal women had significantly lower values of T, fT, A 3 alpha-diol G, FAI and 3 alpha diolG/T but not SHBG and fT/T than cyclic women. When we compared women smokers and nonsmokers, women smokers had serum levels of T, fT, SHBG, 3 alpha-diol G, and values of FAI, fT/T and 3 alpha diol G/T, similar to those in nonsmokers. Serum A levels were higher in women smokers than in nonsmokers, although the difference was significant only in postmenopausal women. PMID- 1417918 TI - The transfer of phosphatidylserine from rat brain microsomes to mitochondria is regulated by microsomal lipid pattern. AB - We label the phosphatidylserine of rat brain microsomes through the base-exchange reaction and study the export of this lipid to mitochondria in a reconstituted system. We fuse microsomes to liposomes to vary the lipid composition of donor membranes and investigate the effect of membrane lipid pattern on phosphatidylserine movement. The specific radioactivity of the phosphatidylserine transferred to mitochondria is higher than that of microsomal phosphatidylserine. This finding supports the hypothesis that the lipid is compartmented in microsomes and that the radioactive, newly synthesized phosphatidylserine is much better exported than the bulk of microsomal phospholipid. The transfer of phosphatidylserine from microsomes, where it forms through the base-exchange reaction, to mitochondria, where it decarboxylates to phosphatidylethanolamine, is enhanced by phosphatidylserine itself, and by other lipid classes. This is proposed as a part of a possible mechanism for regulating phosphatidylserine metabolism in the brain. PMID- 1417919 TI - Chemical modification of the monkey brain cytosolic aminopeptidase that cleaves enkephalin to its constituent amino acids. Evidence for essential tyrosine residue (residues). AB - A cytosolic monkey brain aminopeptidase is known to cleave amino acids sequentially from the amino termini of peptides like enkephalins, angiotensins, and tuftsin. This enzyme is stimulated by ATP-Mg2+ and inactivated by cyclic AMP dependent phosphorylation. Chemical modification of this aminopeptidase by several amino acid-modifying agents indicated essential lysine, histidine, arginine, cysteine, and tyrosine residues. The involvement of tyrosine residues in the catalytic activity was confirmed by modification by N-acetylimidazole and acetic anhydride, hydroxylamine treatment, and absorbance studies. Moreover, acetic-1-14C anhydride could label the enzyme that was inhibited by ATP or by bestatin, a competitive inhibitor of the enzyme. PMID- 1417920 TI - Acidic tripeptidyl aminopeptidase in rat liver tritosomes: partial purification and determination of its primary substrate specificity. AB - We have found the enrichment in rat liver tritosomes of an enzyme which hydrolyzed the synthetic substrate, Ala-Ala-Phe-pNA, under acidic conditions. The enzyme cleaved the substrate in an exopeptidolytic manner, releasing Ala-Ala-Phe. The enzyme was solubilized from tritosomes and partially purified. Beside Ala-Ala Phe-pNA, the obtained enzyme was shown to cleave angiotensin III (Arg-Val-Tyr-Ile His-Pro-Phe) and des-1Tyr-dynorphin A 1-8 (Gly-Gly-Phe-Leu-Arg-Arg-Ile) with tripeptide units. The results obtained suggested that the enzyme preferred an aromatic amino acid at the third position of a substrate peptide. PMID- 1417921 TI - Oxidative modification of lactate dehydrogenase by a non-enzymatic metal ion catalyzed oxidation system. AB - Exposure of lactate dehydrogenase from rabbit muscle to the Fe(III)/EDTA/ascorbate oxidation system leads to a time-dependent enzymatic inactivation (rate of inactivation of 7.35 x 10(-3) min-1), as well as to a spontaneous fragmentation of the protein. Fe(III) is the most important compound in this system, having the highest inactivating effects at concentrations above 10 microM. The substrate pyruvate and the products of the enzymatic reaction, when added at high concentration to the full mixture of the system, have a partial protective effect on the catalytic activity. PMID- 1417922 TI - Different interactions of spermine with a "curved" and a "normal" DNA duplex: (CA4T4G)n and (CT4A4G)n. Gel electrophoresis and circular dichroism studies. AB - Two nucleotide sequences, (CA4T4G)n and (CT4A4G)n, are generally considered as prototypes of a "curved" and a "normal" DNA duplex on the basis of their different behaviour with respect to physico-chemical and/or biochemical properties. We have studied their gel electrophoretic mobilities in the presence of the biologically significant tetracation spermine and have found that spermine causes a decrease of the gel electrophoretic mobility of "curved" DNA, but does not influence that of "normal" DNA. Circular dichroism spectra of the complexes between spermine and the two examined DNAs show dramatically different features. These findings suggest that different DNA superstructures are relevant in interactions not only with proteins, but also with polycations, such as spermine. PMID- 1417923 TI - Effects of low-iron status and deficiency of essential fatty acids on some biochemical constituents of rat brain. AB - The effects of iron and essential fatty acids (EFA) on the development of the brain were studied in young rats. Male weanling rats were maintained on diets deficient in EFA, low in iron (9 ppm) or deficient in both EFA and iron. The low iron status aggravated signs of EFA deficiency indicating decreases in both growth and brain weight. While the protein content of the brain was considerably reduced, the alkaline phosphatase (ALP) activity increased in all dietary regimes. The lipids and fatty acid components of the brain were affected both qualitatively and quantitatively by the diets. Myelin lipids and docosahexaenoic acid (DHA, 22:6) were reduced by the iron deficient diets and the effect was found to be greater in the deficiency of both EFA and iron. It appears that dietary iron has a significant role to play in the biosynthesis of prostaglandins and in the proper configurational development and functioning of the brain. PMID- 1417924 TI - Stimulation of prostaglandin production in rat thymic epithelial cells by protein kinase C mediated activation of phospholipase A2. AB - Tumor promoter (phorbol-12-myristate-13-acetate:PMA) stimulates the production of prostaglandin E2 (PGE2) in a dose- and time-dependent manner in cloned rat thymic epithelial cells, TEA3A1. This stimulation of PGE2 production by PMA was blocked by pretreatment of cells with protein kinase C (PKC) inhibitor staurosporin and was abolished in PKC down modulated cells. PMA treatment significantly stimulated the release of arachidonic acid from the cells, but had no effect on arachidonic acid incorporation and on cyclooxygenase enzymatic activity of the cells. These results indicate that PMA stimulates PGE2 production through PKC mediated activation of phospholipase A2 (PLA2) in thymic epithelial cells. PMID- 1417925 TI - The sea bream liver contains receptors for growth hormone and prolactin. AB - Different tissues of the black sea bream Mylio macrocephalus including the liver, gills, intestine, muscle, gonad, swim bladder, spleen, heart and kidney were examined for the presence of prolactin and growth hormone receptors. Membranes were prepared from the tissues and 125I-labeled ovine prolactin and bovine growth hormone were used as ligands. It was found that the liver contained the highest level of specific 125I-labeled ovine prolactin and bovine growth hormone binding, suggesting the existence of hepatic prolactin and growth hormone receptors. The protein nature of the hepatic growth hormone receptor was revealed by the reduction of specific 125I-labeled growth hormone binding after treatment of hepatic membranes with trypsin and chymotrypsin. PMID- 1417926 TI - Anti-oxidant status in an in vitro model for hyperglycaemic lens cataract formation: competition for available nicotinamide adenine dinucleotide phosphate between glutathione reduction and the polyol pathway. AB - The level of NADPH, total glutathione and sorbitol have been measured in a normal (5mM) and hyperglycaemic (35mM glucose) in vitro rat lens model. In hyperglycaemic conditions, these intermediates are 50%, 84% and 3628% of the normal level. When oxidatively stressed with H2O2 (0.1mM-1.0mM) a gradation in the NADPH and total glutathione decrease is seen, at both glucose levels. This effect is most pronounced in lenses incubated in 35mM glucose, with levels already decreased, the NADPH falls to 15% of the normal lens. Sorbitol levels are correspondingly lower when the lens is oxidatively stressed. The inclusion of the ethyl ester of glutathione alleviates the disruption in anti-oxidant status caused by H2O2 but is unable to restore the NADPH level depleted by hyperglycaemia. These results are discussed in relation to the competitive requirements for NADPH between anti-oxidant preservation and sorbitol formation, as a mechanism for lens opacification in diabetes. PMID- 1417927 TI - Zidovudine-induced blockade of the expression and function of the erythropoietin receptor. AB - Treatment of bone marrow progenitor cells (BMPC) with zidovudine (AZT) at various concentrations (0.5 to 20 microM) in vitro for 24 hr caused a concentration dependent decrease in erythropoietin (Epo) receptor expression. The decrease in Epo receptors correlated with a decline in mRNA levels of the receptor. These results suggest that AZT-induced down-regulation of Epo receptor expression followed by loss of Epo-receptor mediated signal transduction is a significant contributory factor to AZT-induced erythroid toxicity. PMID- 1417928 TI - The pharmacokinetics of 125I-atrial natriuretic factor in anaesthetized rats. Effects of neutral endopeptidase inhibition with candoxatrilat and of ANF-C receptor blockade. AB - The effects of candoxatrilat (cis-4-([2-carboxy-3-(2-methoxyethoxy)propyl]-1 cyclopentanecarbonyla mino)- 1-cyclohexane carboxylic acid) and the ring-deleted atrial natriuretic factor (ANF) analogue C-ANF4-23 (des[Gln18, Ser19, Gly20, Leu21, Gly22]ANF4-23-NH2) on the clearance of (3-[125I]iodotyrosyl28)ANF (125I ANF) were studied in both intact and nephrectomized anaesthetized rats. HPLC analysis was used to verify that the 125I-labelled material isolated by solid phase extraction of rat plasma was intact ANF. In intact animals, clearance of 125I-ANF was biphasic with a T1/2 alpha of 17 sec and T1/2 beta of 95 sec. Volume of distribution (Vd) was 564 mL/kg and plasma clearance (Clp) 248 mL/min/kg. Candoxatrilat, over the dose range 0.01-10 mg/kg i.v., increased T1/2 beta (by a maximum of 56%) and decreased Clp (by up to 52%) with no effect on T1/2 alpha or Vd. C-ANF4-23 (10 micrograms/kg+1 microgram/kg/min i.v.) reduced Vd (by 57%) and Clp (by 54%) with no effect on T1/2 beta, whilst abolishing the T1/2 alpha phase in over 50% of animals. Increasing the dose of C-ANF4-23 did not increase the effect on any of these parameters, apart from a small increase in T1/2 beta. Combining the two agents resulted in a substantial decrease in Clp (76%) whilst the reduction in Vd and increase in T1/2 beta were comparable to those seen with C-ANF4-23 and candoxatrilat alone, respectively. In nephrectomized rats, the pharmacokinetics of 125I-ANF and the changes induced by candoxatrilat were similar to those observed in intact animals, whilst the effects of C-ANF4-23 alone were greater than in intact animals. The combination of C-ANF4-23 and candoxatrilat again produced a substantial increase in T1/2 beta (153%) and decreases in Vd (55%) and Clp (78%) in nephrectomized animals, although these changes could not be distinguished from those seen in intact animals treated with the same combination. Our studies indicate that neutral endopeptidase and ANF-C receptors are both major, and approximately equal, clearance mechanisms for 125I ANF, together accounting for at least 75% of the total clearance of this peptide in the rat. PMID- 1417929 TI - Studies of in vivo iron mobilization by chelators in the ferrocene-loaded rat. AB - The oral efficacy of the oral iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (CP20), 1,2-diethyl-3-hydroxypyrid-4-one (CP94) and desferrioxamine B (DFO) has been compared with intraperitoneal DFO in an experimental model of iron overload with similar biochemical and biophysical characteristics to those observed for human genetic haemochromatosis. The hepatic iron stores in the ferrocene-loaded rat were relatively stable and did not decrease at the end of the loading period. In contrast, the iron dextran rat model showed a rapid depletion of its iron stores 2 weeks after cessation of intraperitoneal injection. When CP20 and CP94 were administered to the ferrocene-loaded rat model in combination with an iron free diet there were significant decreases in (i) total homogenate iron and (ii) hepatic ferritin iron when compared to the iron-loaded rat receiving the iron free diet alone. Desferrioxamine, when administered by gavage, only showed chelation of ferritin iron, while intraperitoneal injection of desferrioxamine showed significant depletion of iron both in the total homogenate and ferritin. Subcellular fractionation of the hepatic organelle clearly showed that where there was depletion of homogenate iron there was a net decrease in the lysosomal fraction, while changes in ferritin iron were reflected by decreases in the cytosolic iron content. Although no assessment of net iron excretion was made, we suggest that the use of this animal model should ascertain the site of chelation by iron chelators. PMID- 1417930 TI - Competition between paraquat and putrescine for uptake by suspensions of rat alveolar type II cells. AB - Paraquat and the structurally similar polyamines, such as putrescine and spermidine, are accumulated actively and selectively by the alveolar type II cells via the polyamine uptake system. We report the uptake kinetics of paraquat and putrescine and their mutual inhibition in freshly isolated rat type II cell suspensions. The uptake of paraquat by type II cells exhibited saturation kinetics and could be inhibited in a concentration-dependent manner by putrescine. By applying enzyme kinetic analysis to our experimental data it was demonstrated that the uptake of paraquat or putrescine is inhibited in a partially competitive manner by the respective inhibitor. Thus, we postulate that the polyamine uptake pathway in type II cells for paraquat and putrescine has two separate sites, one for each substrate, and that binding of one leads to a conformational change in the other. PMID- 1417931 TI - Cytotoxic effects of phenyl-hydroquinone and some hydroquinones on isolated rat hepatocytes. AB - The cytotoxic effects of phenyl-hydroquinone (PHQ) and some other hydroquinones on freshly isolated rat hepatocytes were investigated. Addition of PHQ (0.5 or 0.75 mM) to the hepatocytes elicited dose-dependent cell death accompanied by losses of intracellular glutathione (GSH), protein thiols and ATP. These effects were related to both PHQ loss and phenyl-benzoquinone (PBQ) formation in the cell suspension. The cytotoxicity of PHQ was prevented by sulphydryl compounds such as cysteine and GSH. In Krebs-Henseleit buffer without cells, loss of PHQ (0.5 mM; initial concentration) and formation of PBQ, monitored by spectral measurements, were inhibited by addition of 50 microM GSH. Further, the oxygen consumption owing to autoxidation of PHQ (0.5 mM) in Krebs-Henseleit buffer without cells was depressed by addition of 50 microM GSH. Among all the hydroquinones tested (at 0.5 mM), tert-butyl-hydroquinone and PHQ were most toxic, followed by hydroquinone and 2,5-di(tert-butyl)-1,4-benzohydroquinone. However, accumulation of cellular malondialdehyde was not affected by these hydroquinones. The toxicity was related to the rate of oxygen consumption by each hydroquinone in the buffer. These results suggest that hydroquinone-induced cytotoxicity is dependent on the rate of oxidation of these compounds as well as the loss of protein thiols. PMID- 1417932 TI - Effects of snake venom phospholipase A2 toxins (beta-bungarotoxin, notexin) and enzymes (Naja naja atra, Naja nigricollis) on aminophospholipid asymmetry in rat cerebrocortical synaptosomes. AB - The effects of snake venom phospholipase A2 (PLA2) toxins (beta-bungarotoxin, notexin) and PLA2 enzymes (Naja nigricollis, Naja naja atra) on aminophospholipid asymmetry in rat cerebrocortical synaptic plasma membranes (SPM) were examined. Incubation of intact synaptosomes with 2 mM 2,4,6-trinitrobenzene sulfonic acid (TNBS) for 40 min, under non-penetrating conditions, followed by SPM isolation, allowed us to calculate the percentage of phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the outer leaflet of the SPM, while incubation with disrupted synaptosomes provided total labeling values with the difference representing labeling of the inner leaflet. We found that 30% of the PE and 2% of the PS were in the outer leaflet, with 54% of the PE and 80% of the PS in the inner leaflet; 16% of the PE and 18% of the PS was inaccessible to TNBS. PLA2 toxins and enzymes increased in a concentration-dependent manner the percentage of PS and, to a lesser extent, the percentage of PE in the outer leaflet of the SPM, due to a redistribution from the inner to the outer leaflet. There was no correlation between the PLA2 enzymatic activities and the increased percentage of PS in the outer leaflet of the SPM induced by the PLA2 toxins and enzymes. Alteration of aminophospholipid asymmetry does not explain the greater presynaptic specificity and potencies of the PLA2 toxins as compared to the PLA2 enzymes, but may be associated with the increased acetylcholine release from synaptosomes induced by both the toxins and enzymes. PMID- 1417933 TI - Gold complexes and activation of human polymorphonuclear leukocytes. Dissociation of changes in membrane potential and oxidative burst. AB - The effects of the gold compounds on the alteration of membrane potential of polymorphonuclear leukocytes (PMN) in response to various stimulants have been compared with their effects on the oxidative burst. The present studies have shown that gold complexes [auranofin (AF), aurothiomalate (Autm), aurocyanide (Au(CN)2-)] have contrasting effects on the membrane potential of 3,3' dipentyloxacarbocyanine [di-O-C5(3)] loaded PMN. Au(CN)2- at concentrations which inhibit the oxidative burst of PMN did not affect the membrane depolarization after activation of PMN by phorbol myristate acetate (PMA) and N-formyl-methionyl leucyl phenylalanine (FMLP); Autm slightly stimulated the oxidative burst but had no effect on the depolarization of PMN. In contrast, AF inhibited the depolarization of stimulated PMN to an extent depending upon the concentration of AF, the time of preincubation and the stimulus. The membrane depolarization of PMN caused by PMA, FMLP and concanavalin A (ConA) was inhibited by AF (5 microM) but the depolarization induced by calcium ionophore (A23187) was not affected. AF at the same conditions inhibits the oxidative burst of PMN induced by all these single stimuli including the calcium ionophore. Dissociation of membrane depolarization and superoxide generation caused by AF was also seen in PMN activated by two stimuli. AF (5 microM) had little initial inhibitory effect on the oxidative burst of PMN stimulated by combinations of PMA and ConA or PMA and FMLP whereas it almost totally blocked the depolarization caused by these combinations. Preincubation of cells with 5 microM AF for less than 5 min prior to the addition of PMA allowed membrane depolarization which was followed rapidly by repolarization. None of the gold complexes studied had any effect on the resting membrane potential of PMN. PMID- 1417934 TI - Inhibition of biliary lipid and protein secretion by cyclosporine A in the rat. AB - We investigated the effect of cyclosporine A (CyA) administered as a single i.v. dose of 20 and 40 mg/kg body wt, on biliary secretion of cholesterol, phospholipid, bile acid, and lysosomal marker and canalicular plasma membrane marker enzymes in anaesthetized Wistar rats. CyA reduced the concentration and biliary secretion of cholesterol, phospholipid and bile acid to a considerable extent; the inhibitory effect of CyA on the biliary secretion of phospholipid and bile acid was greater than that on cholesterol. The biliary outputs of acid phosphatase (AcP) and gamma-glutamyltransferase (gamma-GT) were also diminished by the drug, all these effects being dose-dependent. Maximum decreases in bile acid secretion were observed 10 min after administration, whereas those of cholesterol and phospholipid were delayed. Bile acid concentrations and secretion returned to pretest values at 30-50 min after CyA injection whereas those of cholesterol and phospholipid remained significantly reduced at this time point. The greater inhibitory effect of CyA on the biliary outputs of phospholipid and bile acid relative to cholesterol secretion together with the asynchronous fall and recovery of bile acid, cholesterol and phospholipid concentrations and secretion alter the cholesterol/bile acid, phospholipid/bile acid and cholesterol/phospholipid molar ratios as well as the lithogenic index, thus suggesting that CyA would uncouple biliary lipid secretion from bile acid secretion. Since under physiological conditions biliary lipid and gamma-GT secretion is related to and dependent upon bile acid secretion, we propose that the CyA-induced inhibition on lipid and gamma-GT secretion is, at least partly, secondary to the fall in bile acid output caused by the drug. However, since CyA inhibits secretory processes independent of the hepatobiliary flux of bile acid, such as the exocytic discharge of AcP, and because it also uncouples biliary lipid from bile acid secretion, other mechanisms and factors involved in lipid and protein secretion (such as intracellular transport, canalicular membrane fluidity and/or intracanalicular events) might also be altered by this drug. PMID- 1417935 TI - In vitro DNA synthesis by DNA polymerase I and DNA polymerase alpha on single stranded DNA containing either purine or pyrimidine monoadducts. AB - The capacity of the large fragment of DNA polymerase I from Escherichia coli and of DNA polymerase alpha from Drosophila embryo to replicate single-stranded M13mp10 DNA containing either purine or pyrimidine monoadducts was compared. The monoadducts were respectively induced by cisplatinum and by furocoumarin photoaddition. For both types of lesions, it is observed that the eukaryotic enzyme is more inhibited than the prokaryotic one. By mapping the arrest sites produced by furocoumarin monoadducts on the synthesis catalysed by DNA polymerase alpha, we show that, in contrast with the photoreaction observed with double stranded DNA, these compounds do not show a strong sequence specificity in reacting with single-stranded DNA. PMID- 1417936 TI - Events that precede and that follow S-(1,2-dichlorovinyl)-L-cysteine-induced release of mitochondrial Ca2+ and their association with cytotoxicity to renal cells. AB - Previous studies showed that S-(1,2-dichlorovinyl)-L-cysteine perturbs intracellular Ca2+ homeostasis [Vamvakas et al., Mol Pharmacol 38: 455-461, 1990]. The objective of the present study was to investigate the cellular events that precede and that follow S-(1,2-dichlorovinyl)-L-cysteine-induced mitochondrial Ca2+ release. In incubations with isolated kidney mitochondria, S (1,2-dichlorovinyl)-L-cysteine-induced Ca2+ efflux is preceded by increased oxidation of mitochondrial pyridine nucleotides and is prevented by ATP, an inhibitor of the hydrolysis of pyridine nucleotides, and by meta iodobenzylguanidine, an acceptor of ADP-ribose moieties. In LLC-PK1 cells, elevation in the cytosolic Ca2+ concentration is followed by a several-fold increase in DNA double-strand breaks which is attributed to the activation of Ca2+- and Mg(2+)-dependent endonucleases. The formation of DNA double-strand breaks is followed by increased poly(ADP-ribosylation) of nuclear proteins. S (1,2-Dichlorovinyl)-L-cysteine-induced cytotoxicity in LLC-PK1 cells is blocked by chelation of cytosolic Ca2+ with Quin-2, by inhibition of DNA fragmentation with aurintricarboxylic acid and by inhibition of increased poly(ADP ribosyl)transferase activity by 3-aminobenzamide. These findings indicate that S (1,2-dichlorovinyl)-L-cysteine bioactivation in renal cells may initiate the following cascade of events: increased oxidation and hydrolysis of mitochondrial pyridine nucleotides resulting in the modification of mitochondrial membrane proteins by pyridine nucleotide-derived ADP-ribose moieties, followed by Ca2+ release. Elevated Ca2+ concentrations may activate Ca(2+)-dependent endonucleases, which leads to DNA fragmentation followed by increased poly(ADP ribosylation) of nuclear proteins and, finally, cytotoxicity. PMID- 1417938 TI - Inhibition of enzymatic activity of phospholipases A2 by minocycline and doxycycline. AB - Extracellular phospholipases A2 play an important role in articular and extra articular inflammatory processes. Secretory non-pancreatic phospholipase A2 (PLA2) has been implicated in the pathogenesis of articular inflammation in rheumatoid arthritis, whereas pancreatic PLA2 contributes to the tissue damage associated with acute pancreatitis. Since in experimental models lipophilic tetracyclines such as minocycline and doxycycline are antiinflammatory, we examined their effects on PLA2 activity using two assay systems in vitro. We found that minocycline and to a lesser degree doxycycline were markedly inhibitory to both pancreatic and non-pancreatic PLA2. Using [14C]oleic acid labeled Escherichia coli membrane phospholipids as substrate, the IC50 values for minocycline and doxycycline were 3.6 x 10(-5) M (18 micrograms/mL) and 0.98 x 10( 4) M (47 micrograms/mL), respectively. In a scooting mode assay using the synthetic phospholipid 1-palmitoyl-2-(10-pyrenedecanoyl)-3-L-phosphatidylmethanol as substrate, IC50 values for minocycline were 5 microM (2.47 micrograms/mL) for non-pancreatic PLA2 and 8 microM (3.95 micrograms/mL) for pancreatic PLA2. Addition of excess calcium up to 50 mM did not reverse the inhibitory activity of tetracyclines. We conclude that lipophilic tetracyclines inhibit PLA2, probably by interaction with the substrate, and may be a useful adjunct in the therapy of inflammatory conditions in which PLA2 is implicated pathogenetically. PMID- 1417937 TI - Heart and liver membrane phospholipid homeostasis during acute administration of various antitumoral drugs to the rat. AB - The purpose of this study was to investigate in the rat heart and liver the effects of an acute administration of three anthracyclines, doxorubicin, epirubicin and pirarubicin, and an anthracenedione, mitoxantrone, on the membrane peroxidative status, which was estimated by the composition of polyunsaturated fatty acids (PUFA), and on the activities of the enzymes involved in membrane repair processes and lipid hydroperoxide detoxification. Rats were injected for four consecutive days with the drugs or saline (control) and killed 24 hr after the last injection. All the drugs induced an increase in plasma thiobarbituric reactive substances and alpha-tocopherol concentrations, both expressed per milligram of plasma lipids. Plasma vitamin A was decreased by about a factor of two by all the drugs. The fatty acid profile in the heart lipids showed that the polyunsaturated species (20:4 n-6, 22:6 n-3) remained at the same or even higher levels after anthracycline treatment. This can be explained by the fact that the activities of the enzymes involved in either the recycling of membrane phospholipids, such as phospholipases A1 and A2 (EC 3.1.1.4 and EC 3.1.1.32), lysophospholipases (EC 3.1.1.5) and acylCoA:lysophosphatidylcholine acyltransferases (EC 2.3.1.23), or hydroperoxide detoxification, such as selenium dependent glutathione peroxidase (GSH-PX, EC 1.11.1.9) and glutathione S transferases (GSH-T, EC 2.1.5.18), were maintained at the same level of activity after the antitumoral treatment. In liver, membrane phospholipid levels of PUFA were maintained as well as the activities of phospholipid-metabolizing enzymes. GSH-PX activity was not affected whereas that of GSH-T was slightly lowered by the drugs. These results suggest that during acute antitumoral-induced lipid peroxidation of membranes, the multi-enzymatic complex of the immediate processes of repair and detoxification is fully operational, allowing the membrane to rapidly recover its functional status. The results are discussed in the context of the equivocal relationships between antitumoral-induced lipid peroxidation and cardiac disturbances. PMID- 1417939 TI - Ethylbenzene-mediated induction of cytochrome P450 isozymes in male and female rats. AB - Male and female Holtzman rats were exposed to ethylbenzene, and the effect on liver microsomal activities was studied. Hydrocarbon- and sex-dependent effects on P450-dependent metabolism of drugs and aromatic hydrocarbons were investigated. Hydrocarbon treatment produced two patterns of induction in cytochrome P450-dependent activities: (1) induction common to both sexes; and (2) induction exclusively in females. Benzphetamine N-demethylation, 7-ethoxycoumarin O-deethylation, p-nitroanisole O-demethylation and aromatic hydroxylation of toluene were induced in both sexes after rats were exposed to ethylbenzene. The rate of benzphetamine N-demethylation increased 4-fold in females and nearly doubled in males. The increase in O-deethylation of 7-ethoxycoumarin was 3-fold in females and doubled in males, while p-nitroanisole O-demethylation increased 4 fold in both sexes after exposure to ethylbenzene. Ethylbenzene had its greatest effect upon the formation of aromatic hydroxylated metabolites of toluene. Ethylbenzene exposure increased the rate of o-cresol formation by 4- and 9-fold in female and male rats, respectively. The formation rate of p-cresol was undetectable in either sex prior to hydrocarbon exposure; however, after the rats were given ethylbenzene, rates increased to 0.4 nmol/min/mg protein in females and to 0.9 nmol/min/mg protein in the males. Ethylbenzene exposure selectively induced aminopyrine demethylation, aniline hydroxylation, N,N-dimethylnitrosamine N-demethylation (DMNA) and aliphatic hydroxylation of toluene in females. Rates for aminopyrine, aniline, and DMNA were increased 50% over controls, while formation of benzyl alcohol from toluene was enhanced to 260% of control. Western immunoblotting indicated that ethylbenzene treatment induced cytochrome P450 2B1/2B2 to a greater extent in male rats and cytochrome P450 2E1 only in females. Ethylbenzene exposure did not affect significantly the level of cytochrome P450 1A1. PMID- 1417940 TI - Effects of perfluoro fatty acids on xenobiotic-metabolizing enzymes, enzymes which detoxify reactive forms of oxygen and lipid peroxidation in mouse liver. AB - Male mice were exposed via their diet to perfluoro fatty acids of various chain lengths (2-10 carbon atoms) at different doses (0.02 and 0.1% weight) and for different periods of time (2-10 days). Thereafter, we monitored effects on liver and body weights and a number of hepatic parameters, including mitochondrial protein content, microsomal contents of cytochromes P450 and b5, NADPH-cytochrome P450 reductase activity [measured as NADPH-cytochrome c reductase (EC 1.6.2.3)], microsomal and cytosolic epoxide hydrolase (EC 3.3.2.3) activities, cytosolic DT diaphorase (EC 1.6.99.2), glutathione transferase (EC 2.5.1.18), glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities, and levels of thiobarbituric acid-reactive material (as an indicator of lipid peroxidation) in the mitochondrial subfraction. The most dramatic changes observed were a 5-9-fold increase in mitochondrial protein, a 3-6-fold increase in the microsomal content of cytochrome P450, a 3-10-fold increase in cytosolic DT-diaphorase activity, an approximately 2-fold increase in cytosolic epoxide hydrolase activity and as much as a 60% decrease in the level of thiobarbituric acid-reactive compounds in the mitochondrial fraction. Smaller increases in microsomal epoxide hydrolase activity and decreases in cytosolic glutathione peroxidase activity were also observed. Of the perfluoro fatty acids tested, perfluorooctanoic acid caused the largest changes in the parameters examined here. Dietary exposure of mice to a 0.02% dose of this substance for 10 days results in a maximal or near-maximal effect in most cases. PMID- 1417941 TI - The role of lipid peroxidation in the nephrotoxicity of cisplatin. AB - The possible role of lipid peroxidation in the nephrotoxicity of the antitumour drug cisplatin was studied in vitro. In contrast to Adriamycin, cisplatin did not induce lipid peroxidation in rat kidney microsomes containing a NADPH-generating system. Pretreatment of rat kidney microsomes with cisplatin did not reduce the activity of a microsomal glutathione (GSH)-dependent protective factor against lipid peroxidation induced by Fe(2+)-ascorbate. However, pretreatment of rat kidney microsomes with 0.1 mM N-ethyl maleimide (NEM) did reduce this GSH dependent protection. Cisplatin also did not reduce the activity of a cytosolic GSH-dependent protective factor against Fe(2+)-ascorbate-induced lipid peroxidation. The results of our experiments indicate that, in contrast to Adriamycin, cisplatin does not induce lipid peroxidation in vitro in various test systems. It also does not destroy microsomal and cytosolic GSH-dependent protective factors against lipid peroxidation. PMID- 1417942 TI - Peptidyl fluoromethyl ketones as inhibitors of cathepsin B. Implication for treatment of rheumatoid arthritis. AB - Peptidyl fluoromethyl ketones (FMKs), with the amino acid sequence Phe-Ala held constant but with variable N-terminal groups, were synthesized and tested for inhibition of the cysteine proteinase cathepsin B. The FMKs were effective in inhibiting cathepsin B activity in vitro. The inhibition was time dependent and was not reversed by dialysis, suggesting covalent modification of the enzyme. Cathepsin B activity present in livers and kidneys of rats treated with FMKs was reduced by 22-91% 4 hr after a single oral dose of 25 mg/kg. The FMKs inhibited the severity of inflammation and the extent of cartilage and bone damage in adjuvant-induced arthritis. These effects were seen during the late-stage of the disease with no effect on onset or incidence of disease. This is consistent with inhibition of protease-mediated damage. These FMKs or derivatives may be of clinical value in the treatment of arthritis. PMID- 1417943 TI - Increase of brain endogenous monoamine oxidase inhibitory activity (tribulin) in experimental audiogenic seizures in rats: evidence for a monoamine oxidase A inhibiting component of tribulin. AB - Brain tribulin activity in rats with an inherited predisposition to audiogenic epilepsy was studied after seizures of different intensity were induced by an electric bell. Weak seizures (from 0 to 2 arbitrary units) did not produce any changes in endogenous inhibitory activity towards either monoamine oxidase (MAO) A or B. Moderate seizures were characterized by increases in both MAO A and MAO B inhibitory activity (up to 1.9-fold). Complete tonic epileptiform seizures with total areflexia (4 arbitrary units) induced further augmentation (up to 2.5-fold) of MAO A but not of MAO B inhibitory activity. This dissociation between the two inhibitory activities points to the existence of a separate MAO A-inhibiting component of brain tribulin which is different from isatin. PMID- 1417944 TI - Inhibition and induction of cytochrome P450 2B1 in rat liver by promazine and chlorpromazine. AB - Phenothiazine tranquilizers have been associated with pharmacokinetic drug interactions in man. In this study the in vivo and in vitro effects of the clinically important phenothiazines promazine (PZ) and chlorpromazine (CPZ) on drug oxidations catalysed by specific cytochrome P450 (P450) enzymes were investigated in the rat. In vitro, the two drugs were relatively ineffective inhibitors of constitutive P450 activities, but were inhibitory toward the principal phenobarbital-inducible P450 2B1 and, to a lesser extent, P450 1A1. Administration of PZ and CPZ to male rats did not markedly influence the total microsomal P450 content of the liver. However, the quantitatively important male specific P450 2C11 was down-regulated by CPZ and concomitant induction of P450 2B1 and associated 7-pentylresorufin O-depentylase activity were noted. A small increase in the activity of microsomal 7-ethylresorufin O-deethylase was also observed following administration of both drugs to rats, suggesting induction of P450 1A1/2. Considered together, it is apparent that the two phenothiazines are preferential inhibitors and inducers of P450 2B1 in rat liver. Drug interactions in humans involving phenothiazines may reflect a combined effect of induction and inhibition processes as well as down-regulation of other P450s, such as that produced by CPZ on P450 2C11. PMID- 1417945 TI - Microsomal cytochrome P450 in human brain regions. AB - Cytochrome P450 (P450) levels were quantitated in microsomes from human brain regions obtained at autopsy. The reduced carbon monoxide binding spectra of cortical microsomes showed two absorption maxima at 449 and 425 nm. On solubilization of the microsomes, essentially a single peak was observed at 449 nm. The P450 levels in human brain cortical microsomes varied from 0.03 to 0.12 nmol/mg protein among the seven samples examined. The concentration of the hemeprotein present as nmol/g tissue was highest in the brain stem and cerebellum and lowest in the striatum and hippocampus. PMID- 1417947 TI - Active-site directed irreversible inhibition of diamine oxidase by a homologous series of aziridinylalkylamines. AB - Three electrophilic homologous aminoalkylaziridine analogues of putrescine, cadaverine, and 1,3-diaminopropane were synthesized and found to represent a mechanistically distinct class of irreversible inhibitors of diamine oxidase. The putrescine analogue, N-(4-aminobutyl)aziridine gave the lowest calculated IC50 value, whereas N-(3-aminopropyl)aziridine, an analogue of the poorest substrate of the series, showed the highest IC50. The findings suggest that the aziridinylalkylamines tested are site-directed agents that form irreversible complexes at the active site of diamine oxidase. Affinity of the inhibitors for the active site appeared to be dependent on alkyl chain length, suggesting that binding promotes the reactivity of the aziridinyl group. PMID- 1417946 TI - Reduced carnitine and ketogenesis in the pivampicillin treated rat. AB - Pivampicillin (630 mg/kg body wt) given daily by stomach tube induced carnitine deficiency in the rat. The carnitine concentrations after 24 days were significantly reduced to (mean +/- SD) 34 +/- 2, 27 +/- 7, 70 +/- 18, 75 +/- 16 and 49 +/- 4% of controls in plasma, liver, muscle, heart and kidney, respectively, without any further reduction after 36 days. Pivampicillin treatment reduced the carnitine concentrations in the liver of the 48 hr fasted rat to about 1/2 of the controls after 6 days. The concentration of beta hydroxybutyrate was significantly reduced up to 14 days of treatment, and again increased. There was no significant difference in the free fatty acid concentrations between treated and control rats. Thus, pivampicillin treatment induced carnitine deficiency in the rat, but not as pronounced as seen in humans. This is possibly caused by adjustment of bacterial flora in the gut or altered renal mechanisms. The pivampicillin-treated rat, therefore, is not a useful model for pronounced carnitine deficiency in humans. PMID- 1417948 TI - Effect of various flavonoids on lysosomes subjected to an oxidative or an osmotic stress. AB - When a light mitochondrial fraction (L fraction) of rat liver is incubated in the presence of an oxygen free radical generating system (xanthine-xanthine oxidase), the free activity of N-acetylglucosaminidase (NAGase) increases as a result of the deterioration of the lysosomal membrane. Various flavonoids are able to prevent this phenomenon, others are ineffective. Comparative activity studies suggest the importance of the presence of two OH groups in orthosubstitution in the B ring and of an OH in the 3 position. Flavan-type flavonoids behave like their related flavonoids; d-catechin also opposes lysosome disruption. Kaempferol, quercetin, 7,8-dihydroxyflavone and d-catechin inhibit lipoperoxidation occurring in an L fraction incubated with the xanthine oxidase system as ascertained by malondialdehyde (MDA) production. For kaempferol and quercetin, such an inhibition parallels the prevention of NAGase release; this is not the case for the two other compounds where inhibition of NAGase release takes place at a flavonoid concentration lower than that required to oppose MDA production. Morphological observations performed on purified lysosomes confirm the biochemical results. Some flavonoids are also able to prevent release of NAGase caused by the incubation of an L fraction in isoosmotic glucose. Only flavone and hydroxyflavones are effective. It is proposed that the protective effect of flavonoids on lysosomes subjected to oxygen free radicals does not only originate from their scavenger and antilipoperoxidant properties; a more direct action on lysosomal membrane making it more resistant to oxidative aggression has to be considered. The prevention by some flavonoids of lysosome osmotic disruption in isoosmotic glucose could be the result of an inhibition of glucose translocation through the lysosomal membrane. PMID- 1417949 TI - Stereoselective conjugation of 2-bromocarboxylic acids and their urea derivatives by rat liver glutathione transferase 12-12 and some other isoforms. AB - Glutathione (GSH) conjugation of the separate enantiomers of five 2 bromocarboxylic acids and some of their urea derivatives by rat liver GSH transferases (GSTs) was studied. The liver cytosolic fraction conjugated all compounds, except for (R)-2-bromoisovaleric acid, with a variable degree of stereoselectivity. A GST pool, prepared by S-hexyl-GSH affinity chromatography, conjugated the urea derivatives at a somewhat higher rate but had very little activity towards the carboxylic acids, indicating that much activity towards the latter substrates was due to transferases not bound by the affinity column. Therefore, the activity was studied of some pure GSTs that are bound only slightly by the affinity column towards the separate enantiomers of 2 bromovaleric acid (BV), its urea derivative and 2-bromo-3-phenylpropionic acid (BPP). No activity was detected with transferases 5-5 and 8-8. Transferase 1-1 was active towards all compounds with high activity towards the urea derivatives. Transferase 12-12 showed high, stereospecific activity towards the R enantiomers of BV, its urea derivative and BPP. PMID- 1417950 TI - Cerium-induced strain-dependent increase in Cyp2a-4/5 (cytochrome P4502a-4/5) expression in the liver and kidneys of inbred mice. AB - The murine Cyp2a-4 and Cyp2a-5 genes encode P450 isoforms catalysing testosterone 15 alpha-hydroxylase and coumarin 7-hydroxylase (COH) activities, respectively. Two days after the administration of a hepatotoxic dose of cerium chloride (2 mg/kg i.v.), COH activity was increased 3.2-fold in the liver of DBA/2 mice. Three and 4 days after the cerium treatment, coinciding with the occurrence of overt liver damage, there was a dramatic decrease in COH activity. The activities of testosterone 15 alpha-hydroxylase and the Cyp1a-1-mediated 7-ethoxyresorufin O deethylase (EROD) were decreased in response to cerium. Much less pronounced changes in the enzyme activities occurred in the C57BL/6 mouse liver. Northern blot analysis showed a 21-fold increase in the hepatic Cyp2a-4/5 mRNA in the DBA/2 mice at day 2, whereas no increase occurred in the C57BL/6 mice. Also in the kidneys the increase in COH activity and in Cyp2a-4/5 mRNA was marked only in the DBA/2 mice. A polymerase chain reaction-mediated analysis method utilizing a unique PstI restriction site in the Cyp2a-5 cDNA was used to differentiate between the highly homologous Cyp2a-4 and Cyp2a-5 mRNAs. Cerium was found to increase the amount of hepatic and renal Cyp2a-4 and Cyp2a-5 mRNA only in the DBA/2 mice. These data indicate that the Cyp2a-4/5 complex is regulated in a different way in DBA/2 and C57BL/6 mice and that some association exists between the development of liver damage and COH induction. PMID- 1417951 TI - Increased biliary excretion of glutathione is generated by the glutathione dependent hepatobiliary transport of antimony and bismuth. AB - We have recently demonstrated that the hepatobiliary transport of arsenic is glutathione-dependent and is associated with a profound increase in biliary excretion of glutathione (GSH), hepatic GSH depletion and diminished GSH conjugation (Gyurasics A, Varga F and Gregus Z, Biochem Pharmacol 41: 937-944 and Gyurasics A, Varga F and Gregus Z, Biochem Pharmacol 42: 465-468, 1991). The present studies in rats aimed to determine whether antimony and bismuth, other metalloids in group Va of the periodic table, also possess similar properties. Antimony potassium tartrate (25-100 mumol/kg, i.v.) and bismuth ammonium citrate (50-200 mumol/kg, i.v.) increased up to 50- and 4-fold, respectively, the biliary excretion of non-protein thiols (NPSH). This resulted mainly from increased hepatobiliary transport of GSH as suggested by a close parallelism in the biliary excretion of NPSH and GSH after antimony or bismuth administration. Within 2 hr, rats excreted into bile 55 and 3% of the dose of antimony (50 mumol/kg, i.v.) and bismuth (150 mumol/kg, i.v.), respectively. The time courses of the biliary excretion of these metalloids and NPSH or GSH were strikingly similar suggesting co-ordinate hepatobiliary transport of the metalloids and GSH. However, at the peak of their excretion, each molecule of antimony or bismuth resulted in a co transport of approximately three molecules of GSH. Diethyl maleate, indocyanine green and sulfobromophthalein (BSP), which decreased biliary excretion of GSH, significantly diminished excretion of antimony and bismuth into bile indicating that hepatobiliary transport of these metalloids is GSH-dependent. Administration of antimony, but not bismuth, decreased hepatic GSH level by 30% and reduced the GSH conjugation and biliary excretion of BSP. These studies demonstrate that the hepatobiliary transport of trivalent antimony and bismuth is GSH-dependent similarly to the hepatobiliary transport of trivalent arsenic. Proportionally to their biliary excretion rates, these metalloids generate increased biliary excretion of GSH probably because they are transported from liver to bile as unstable GSH complexes. The significant loss of hepatic GSH into bile as induced by arsenic or antimony may compromise conjugation of xenobiotics with GSH. PMID- 1417952 TI - Is there an association between an increase in c-myc RNA steady state levels and c-myc methylation in HL-60 cells treated with 3-deaza-(+/-)-aristeromycin, an indirect inhibitor of methylation? AB - Alteration in gene expression of the proto-oncogene c-myc in HL-60 cells is associated with differentiation of these cells. We have studied the steady state levels of c-myc transcripts, the levels of transmethylation metabolites S adenosylmethionine and S-adenosyl-homocysteine and the methylation pattern of the c-myc gene after treatment of HL-60 cells with the transmethylation inhibitor and granulocytic inducer, 3-deaza-(+/-)-aristeromycin. A transient increase in c-myc RNA levels after 45 min of drug exposure was observed which was accompanied by changes in the ratio of transmethylation metabolites in both whole cells and nuclei. The changes in transmethylation metabolites in whole cells, although compatible with levels frequently associated with hypomethylation of cellular components, caused no changes in methylation of c-myc DNA sequences of the HL-60 cells as detected by HpaII or MspI digestion and Southern blotting. PMID- 1417953 TI - The effects of ibuprofen enantiomers on hepatocyte intermediary metabolism and mitochondrial respiration. AB - In vivo and in vitro (-)R-ibuprofen is inverted to the (+)S antipode via stereoselective formation of an R-ibuprofenyl-CoA intermediate. In this study the effects of (-)R- and (+)S-ibuprofen on metabolism and respiration were studied using isolated rat hepatocytes and mitochondria. R-Ibuprofen significantly increased the lactate to pyruvate ratio, perturbed mitochondrial ketogenesis as evidenced by alterations in the beta-hydroxybutyrate to acetoacetate ratio and uncoupled mitochondrial oxidative phosphorylation. In addition, substantial dose- and time-dependent sequestration of reduced CoA (CoASH) occurred in the presence of the R enantiomer. Similarly, S-ibuprofen altered both the cytosolic and mitochondrial redox states although the magnitude of the effect was substantially less than that observed with the R enantiomer. In contrast to R-ibuprofen, S ibuprofen did not uncouple oxidative phosphorylation or sequester hepatocyte CoASH. It is proposed that the perturbations observed in hepatocyte intermediary metabolism and mitochondrial function are attributable to a combination of the direct effects of R-ibuprofen per se and the sequestration of CoASH as R ibuprofenyl-CoA during the process of chiral inversion. On the basis of these results, R-ibuprofen should be considered more in terms of metabolism to a reactive acyl-CoA intermediate rather than as a pro-drug for the pharmacologically active S-enantiomer. PMID- 1417954 TI - Effect of dietary fat on the in vitro hepatotoxicity of paracetamol. AB - In the present study, we have examined the effect of dietary fat on paracetamol induced liver injury in an in vitro rat liver slice model. Rats were fed, for 7 10 days, diets containing either butter or polyunsaturated vegetable margarine, two fat sources commonly consumed in the human diet. Liver slices were then exposed to paracetamol for 2 hr and further incubated for 4 hr without paracetamol. Cell damage in the slices was quantified at 6 hr by measuring leakage of lactate dehydrogenase, increase in water content and potassium loss. Covalent binding of radioactive paracetamol to liver and the membrane fatty acid composition of the liver were also measured. Liver slices from rats fed butter diets were significantly more sensitive to the toxic effects of paracetamol than those from margarine fed rats. The membrane lipid composition of the livers also reflected the differing fatty acid content of the two diets. PMID- 1417955 TI - Rapid chloroquine efflux phenotype in both chloroquine-sensitive and chloroquine resistant Plasmodium falciparum. A correlation of chloroquine sensitivity with energy-dependent drug accumulation. AB - Recent reports suggest that lower levels of chloroquine accumulation in chloroquine-resistant isolates of Plasmodium falciparum are achieved by energy dependent chloroquine efflux from resistant parasites. In support of this argument, a rapid chloroquine efflux phenotype has been observed in some chloroquine-resistant isolates of P. falciparum. In this study, no relationship was found between chloroquine sensitivity and the rate of [3H]chloroquine efflux from four isolates of P. falciparum with a greater than 10-fold range in sensitivity to chloroquine. All the isolates tested displayed the rapid efflux phenotype, irrespective of sensitivity. However, chloroquine sensitivity of these isolates was correlated with energy-dependent rate of drug accumulation into these parasites. Verapamil and a variety of other compounds reverse chloroquine resistance. The reversal mechanism is assumed to result from competition between verapamil and chloroquine for efflux protein translocation sites, thus causing an increase in steady-state accumulation of chloroquine and hence a return to sensitivity. Verapamil accumulation at a steady-state is increased by chloroquine, possibly indicating competition for efflux of the two substrates. Increases in steady-state verapamil concentrations caused by chloroquine were identical in sensitive and resistant strains, suggesting that similar capacity efflux pumps may exist in these isolates. These data suggest that differences in steady-state chloroquine accumulation seen in these isolates can be attributed to changes in the chloroquine concentrating mechanism rather than the efflux pump. It seems likely that chloroquine resistance generally in P. falciparum, results at least in part from a change in the drug concentrating mechanism and that changes in efflux rates per se are insufficient to explain chloroquine resistance. PMID- 1417956 TI - Potencies of protein kinase C inhibitors are dependent on the activators used to stimulate the enzyme. AB - The aim was to examine systematically the potencies of protein kinase C inhibitors as a function of the kinase activator. Protein kinase C is activated by at least four stimulators: calcium plus phosphatidylserine (Ca/PS), phorbol 12 myristate 13-acetate plus PS (PS/PMA), arachidonic acid plus calcium (Ca/AA) and the synthetic peptide activator PCK530-558. With histone or GS1-12 as substrates, protein kinase C was maximally activated by Ca/PS, or to maxima of 62%, 89% or 82% with PS/PMA, Ca/AA or PKC530-558, respectively. One group of inhibitors, including H-7 and staurosporine, were equipotent, regardless of the activator. All other inhibitors showed variable selectivity, dependent upon the activator. A second group of inhibitors, including sphingosine and lipophosphoglycan, were eight or 200 times more potent for inhibition of PS/PMA-stimulated activity (relative to Ca/PS) and a third group, including retinal and palmitoylcarnitine, were 14 or 262 times more potent towards Ca/PS-stimulated activity. A final group (rhodamine 6G) was nine times more potent when Ca/AA was the activator. Similar results were obtained using the endogenous substrates dephosphin or MARCKS in synaptosol. Phosphorylation of MARCKS was stimulated by PS/PMA or Ca/PS, while phosphorylation of dephosphin was stimulated only by Ca/PS. The phosphorylation of either by Ca/PS-activated kinase was nine times more potently inhibited by palmitoylcarnitine, while phosphorylation of MARCKS by PS/PMA-activated kinase was 10 times more potently inhibited by sphingosine. H-7 inhibited both at similar concentrations. A model encompasses these differences in potency if the inhibitors are divided into four groups (A-D) according to their competitive inhibition with the appropriate activator or at the active site. The non selective inhibitors interact at the active sites of protein kinase C (group A). The compounds which preferentially inhibit PS/PMA-activated kinase (sphingosine and lipophosphoglycan) are competitive inhibitors of PMA and 1,2-diacylglycerol (group B), those selective for Ca/PS-activated kinase (palmitoylcarnitine and retinal) are competitive with PS (group C) and those selective for Ca-AA activation (rhodamine 6G) are likely to be competitive with fatty acid (group D). Therefore, the effectiveness of protein kinase C inhibitors is dependent upon the activator employed. PMID- 1417957 TI - Induction of mutations in V79-4 mammalian cells under hypoxic and aerobic conditions by the cytotoxic 2-nitroimidazole-aziridines, RSU-1069 and RSU-1131. The influence of cellular glutathione. AB - Incubation of the 2-nitroimidazole-aziridine, RSU-1069 [1-(2-nitro-1-imidazolyl) 3-(1-aziridinyl)-2-propanol], and its monomethylaziridine analogue, RSU-1131 [1 (2-nitro-1-imidazolyl)-3-(1-(2-methylaziridinyl))-2-propanol], with V79-4 mammalian cells for 2 hr under aerobic or hypoxic conditions induces mutations as measured at the hypoxanthine phosphoribosyl transferase locus. The ability of these agents to induce mutations is increased by a factor of 12-14 under hypoxic conditions. The increased cytotoxicity of these agents under hypoxic conditions was confirmed following a 2 hr incubation period. Decreasing the glutathione (GSH) content of the cells with buthionine-(S,R)-sulphoximine to < 1% of the control generally results in an increase in the cytotoxicity and mutagenicity of these agents under both aerobic and hypoxic conditions. Since these agents do not modify the cellular GSH levels, it is inferred that the thiols partially detoxify through removal of a reactive metabolite of the agents, under hypoxic conditions, or removal of known DNA adducts, and not through their interaction with the agents themselves. Under aerobic conditions, the formation of mutations is consistent with the established monofunctional action of these agents whereas under hypoxic conditions the bifunctional action predominates for mutation induction, based upon the large differential aerobic:hypoxic effect. From a comparison of the number of mutations per lethal event, the effect of thiol depletion is more pronounced for cytotoxicity than for mutation induction by these agents. In summary, these agents are considered to be weak mutagens towards V79-4 cells under aerobic conditions when compared with other DNA alkylating agents, although they are more potent under anoxic conditions. PMID- 1417958 TI - The relationship between the activity of methionine synthase and the ratio of S adenosylmethionine to S-adenosylhomocysteine in the brain and other tissues of the pig. AB - Using nitrous oxide to inactivate methionine synthase in vivo, the relationship of the activity of methionine synthase to the S-adenosylmethionine (AdoMet)/S adenosylhomocysteine (AdoHcy) ratio was examined in neural and other tissues of the pig. Pigs were exposed to 15% nitrous oxide for varying intervals of up to 7 days or studied at varying intervals of recovery in air after 7 days nitrous oxide inhalation, and the rate of inactivation or resynthesis of methionine synthase was related to the corresponding AdoMet/AdoHcy ratios. The rate of inactivation of enzyme during nitrous oxide exposure was considerably faster in the liver and kidney than in the brain and spinal cord with activity levelling off between 10% and 20% of control values. The AdoMet/AdoHcy ratio fell in all tissues during nitrous oxide treatment, the fall being most marked in the brain and spinal cord where a 10-fold change occurred. This change was attributed mainly to a rise in AdoHcy levels. The recovery pattern of methionine synthase was broadly linear but was slower in the spinal cord (0.10 +/- 0.03% per hr; mean +/- SEM) than in any other tissue examined including brain (0.35 +/- 0.04% per hr). Correspondingly, the recovery of the AdoMet/AdoHcy ratio was also significantly slower in the spinal cord. When values for exposure and recovery were combined there was a significant correlation between the activity of methionine synthase and the AdoMet/AdoHcy ratio in both the brain (r = 0.90; P < 0.001) and the spinal cord (r = 0.92; P < 0.001). These results support the concept that the AdoMet/AdoHcy ratio is closely related to the pathogenic process which produces the neurologic lesions associated with a reduction in methionine synthase activity. PMID- 1417959 TI - Evaluation of iron binding and peroxide-mediated toxicity in rat hepatocytes. AB - A novel assay was developed to determine subnanomolar amounts of Fenton-reactive iron (FRI) in biological tissues. FRI represents that pool of iron that is redox active and capable of participating in a model Fenton reaction. The FRI was used to identify a kinetically-defined cellular iron binding site. This site displays positive cooperativity, with apparent kinetic constants of Kd = 10.6 microM, Bmax = 20.7 nmol/mg protein, and the Hill coefficient = 1.4. After addition of exogenous ferrous ammonium sulfate to hepatocytes, binding occurred within a few seconds and was stable for at least an hour. Free extracellular iron, but not bound iron, stimulated lipid peroxidation in hepatocytes. In contrast, bound but not free iron produced a concentration-dependent increase in tert-butyl hydroperoxide (TBH)-mediated toxicity, suggesting the toxicological relevance of bound, rather than free iron. Furthermore, the hydroxyl radical scavengers mannitol and 2-deoxyribose inhibited Fe2/TBH-mediated lipid peroxidation, but not cell killing, suggesting that hydroxyl radical may not be involved in the critical toxic event. The divalent cations Mn2+ and Co2+ inhibited iron-mediated hepatocyte killing in the presence of TBH, but only if added prior to Fe2+. Mn2+, but not Co2+, inhibited Fe(2+)-mediated lipid peroxidation regardless of the order of addition. These results indicate the existence of a specific, kinetically-defined cellular iron binding site. Such binding is involved in peroxide-mediated toxicity, but independent of lipid peroxidation. The specific nature of this site and involvement with other forms of chemical intoxication or cellular iron homeostasis are unknown. PMID- 1417961 TI - Alterations in ATP-dependent calcium uptake by rat renal cortex microsomes following ochratoxin A administration in vivo or addition in vitro. AB - A disruption of calcium homeostasis, leading to a sustained increase in cytosolic calcium levels, has been associated with cytotoxicity in response to a variety of agents in different cell types. We have observed that administration of a single high dose or multiple lower doses of the carcinogenic nephrotoxin ochratoxin A (OTA) to rats resulted in an increase of the renal cortex endoplasmic reticulum ATP-dependent calcium pump activity. The increase was very rapid, being evident within 10 min of OTA administration and remained elevated for at least 6 hr thereafter. The increase in calcium pump activity was inconsistent with previous observations that OTA enhances lipid peroxidation (ethane exhalation) in vivo, a condition known to inhibit the calcium pump. However, no evidence of enhanced lipid peroxidation was observed in the renal cortex since levels of malondialdehyde and a variety of antioxidant enzymes including catalase, DT diaphorase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione S-transferase were either unaltered or reduced. In in vitro studies, addition of OTA to cortex microsomes during calcium uptake inhibited the uptake process although the effect was reversible. Preincubation of microsomes with NADPH had a profound inhibitory effect on calcium uptake but inclusion of OTA was able to reverse the inhibition. Changes in the rates of microsomal calcium uptake correlated with changes in the steady-state levels of the phosphorylated Mg2+/Ca(2+)-ATPase intermediate, suggesting that in vivo/in vitro conditions were affecting the rate of enzyme phosphorylation. PMID- 1417960 TI - Depletion of a discrete nuclear glutathione pool by oxidative stress, but not by buthionine sulfoximine. Correlation with enhanced alkylating agent cytotoxicity to human melanoma cells in vitro. AB - The existence of a distinct pool of glutathione in the nucleus of cultured human melanoma cells was demonstrated. Melanoma cell nuclei contained 13-35 pmol of glutathione/10(6) nuclei, or approximately 0.4-1.3% of the total cellular glutathione. This nuclear glutathione pool resisted depletion by buthionine sulfoximine, an agent that inhibits glutathione synthesis, but was rapidly and reversibly depleted by subtoxic concentrations of Adriamycin plus carmustine, two agents that promote oxidation of glutathione without permitting its regeneration through enzymatic reduction of glutathione disulfide. The ability of Adriamycin plus carmustine to deplete this small but significant pool of glutathione in the cell nucleus may explain why these agents potentiate the cytotoxic effects of the DNA-alkylating agent melphalan to a much higher degree than does buthionine sulfoximine at concentrations that are equipotent in depleting cytosolic glutathione. PMID- 1417962 TI - Binding of 2-acetylpyridine-5-[(2-chloroanilino)thiocarbonyl] thiocarbonohydrazone (BW348U87) to human serum albumin. AB - Dissociation constants and rate constants for the binding of 2-acetylpyridine-5 [(2-chloroanilino)thiocarbonyl]thiocar bonohydrazone (I, BW348U87), an agent that enhances the antiherpetic efficacy of acyclovir, to human serum albumin have been determined. I quenched the fluorescence of human serum albumin, whereas the absorbance of I at 370 nm increased upon binding to the protein. The absorbance change was attributed to preferential binding of anionic I (pKa 7.0). Titration data indicated multiple binding sites for I. The dissociation constant of the high-affinity site was 0.11 microM. The time course for binding of I to 100 nM human serum albumin was biphasic. The early and late phases were described by first-order rate constants that had maximal values of 100 and 11 sec-1, respectively. The rate constant for the dissociation of I from human serum albumin was estimated to be 6 sec-1. Dodecyl sulfate and octanoate displaced I from human serum albumin.I with rate constants of 4.5 and 7.3 sec-1, respectively. Since the fluorescence emission spectrum of human serum albumin and the absorption spectrum of I overlapped significantly (the spectral overlap integral, J, was 2.6 x 10(-14) M-1 cm3), the possibility of Forster dipole-dipole energy transfer was considered. However, a significant fraction of the fluorescence quenching by I resulted from a conformational change in the protein upon binding of I and was not the result of dipole-dipole energy transfer. Nonetheless, the distance between one of the binding regions for I on human serum albumin and a tryptophan residue in the protein was estimated to be 31 A by this method. The high affinity of I for albumin could be related to its low hematological toxicity. PMID- 1417963 TI - Suppressive effects of the endothelin receptor (ETA) antagonist BQ-123 on ET-1 induced reduction of lipoprotein lipase activity in 3T3-L1 adipocytes. AB - Endothelin (ET)-1 reduced heparin-releasable lipoprotein lipase (LPL) activity in 3T3-L1 adipocytes in a concentration-dependent manner. However, a selective ETB receptor agonist, [Ala1,3,11,15]ET-1, did not act like ET-1. The ET-1-induced decrease in LPL activity was suppressed by a selective ETA receptor antagonist, BQ-123: the concentration-response curve for the ET-1 reduction of LPL activity was shifted to the right in the presence of BQ-123 in a concentration-dependent manner. This antagonistic effect of BQ-123 clarifies that the ETA receptor is responsible for the ET-1-induced reduction of LPL activity in 3T3-L1 adipocytes, which suggests that there is therapeutic potential for ETA antagonists in LPL related lipoprotein disorders. PMID- 1417964 TI - In vitro and in vivo effects of the anti-inflammatory peptides, antiflammins. AB - The anti-inflammatory synthetic polypeptides referred to as antiflammins are thought to be inhibitors of phospholipase A2 (PLA2) (EC 3.1.1.4). These peptides are from the sequence of amino acids of greatest similarity between uteroglobin and lipocortin I. The effect of these peptides was studied on PLA2 activation in rat platelets and on acute inflammatory models after local or parenteral administration of drug. We found that antiflammins decreased collagen-induced platelet activation, but had no effect when arachidonic acid was used as activator. The peptides were able to inhibit acute inflammatory processes induced by carrageenan or phorbol esters when administered locally or parenterally. However, antiflammins had no effect on inflammation induced by exogenous PLA2 administration. These results indicate that the antiflammins may have a direct inhibitory effect on PLA2 activation but not on the enzyme or enzyme-substrate interaction. PMID- 1417965 TI - Inactivation of yeast alcohol dehydrogenase by alkylperoxyl radicals. Characteristics and influence of nicotinamide-adenine dinucleotides. AB - The study of the interaction of alkylperoxyl radicals generated by the aerobic thermolysis of 2,2'-azobis(2-amidinopropane) (AAP) with yeast alcohol dehydrogenase (YADH) revealed a high reactivity of the enzyme, with an average of about 20 radicals per added YADH tetramer being needed to elicit its total inactivation. NAD+ enhanced YADH inactivation at NAD+/YADH molar ratios from 0.25 to 1, decreasing the rate of the process when added in excess to the enzyme concentration. At NADH/YADH molar ratios greater than 1, NADH exhibited a protective effect characterized by a poorly defined induction time and lower inactivation rates, which progressively increased during the reaction period. These changes occurred concomitantly with the oxidation of NADH into NAD+, which might counteract the protective effect of NADH. Under similar conditions, NADP+ did not modify AAP-induced YADH inactivation, while NADPH exhibited a modest protection at NADPH/YADH molar ratios greater than 1. It is concluded that YADH inactivation by alkylperoxyl radicals is strongly dependent on the redox state of the NADH-NAD+ couple, as the rates of the process at different time intervals inversely correlate with the respective NADH/NAD+ ratios. PMID- 1417966 TI - Effect of serum-free medium on cytochrome P450-dependent metabolism and toxicity in rat cultured hepatocytes. AB - Cytochrome P450 (P450)-dependent activities in homogenates of rat hepatocytes cultured for 96 hr in serum-free and serum-containing medium were compared. Benzphetamine and erythromycin N-demethylases, 7-methoxy- and propoxy-coumarin O dealkylases, p-nitrophenol hydroxylase and 7-ethoxy- and pentoxy-resorufin O dealkylases were all maintained at higher levels in hepatocytes cultured in serum free medium, although there was some selectivity with respect to the extent of the maintenance relative to the activities in fresh cells. The toxicities of coumarin, precocene I and precocene II to 24 hr hepatocyte cultures, determined as decreased survival, were also shown to be increased in serum-free medium. However, the magnitude of the difference between media with respect to the toxicity of precocene II was decreased in hepatocytes cultured for 72 hr. The observed increase in toxicity is consistent with the improved maintenance of P450 in hepatocytes cultured in serum-free medium, although there is still a selective decline in P450 activities and toxicity with increased time in culture. The activity of alcohol dehydrogenase and the toxicity of allyl alcohol were similar in hepatocytes cultured in serum-free and serum-containing medium for 96 hr. The absence of serum did not affect the non-protein sulphydryl content of the cultures. PMID- 1417967 TI - Impairment of mitochondrial 5-aminolevulinic acid synthase activity in Gunn rat liver. AB - Gunn rats are characterized by hereditary hyperbilirubinemia and a decrease, when compared to Wistar rats, in hepatic heme pool size which could result from an alteration of mitochondrial functions. Unconjugated bilirubin present in Gunn rat liver did not modify either the ultrastructural morphology or oxidative metabolism of the mitochondria as compared to those in Wistar rat liver. However, 5-aminolevulinic acid synthase activity is reduced by nearly 40% in Gunn rat liver mitochondria, thus explaining the reduced size of the hepatic heme pool. PMID- 1417968 TI - Influence of palmitate and benzoate on the unidirectional chiral inversion of ibuprofen in isolated rat hepatocytes. AB - The influence of benzoic acid, a typical substrate of medium-chain acyl-CoA synthetase, and of palmitic acid, a substrate of long-chain acyl-CoA synthetase, on the metabolic chiral inversion of ibuprofen was investigated in freshly isolated hepatocytes. It was shown that the conjugation of benzoid to hippuric acid does not influence the chiral inversion of ibuprofen. In contrast, palmitic acid inhibited markedly the R-to-S inversion of ibuprofen. It was concluded that this inhibition is due to competition between (R)-ibuprofen and palmitic acid for long-chain acyl-CoA synthetases. PMID- 1417969 TI - Oxidative metabolism of cinnarizine in rat liver microsomes. AB - The oxidative metabolism of cinnarizine (CZ) [1-(diphenylmethyl)-4-(3-phenyl-2 propenyl)-piperazine] to 1-(diphenylmethyl)piperazine (M-1), 1-(diphenylmethyl)-4 [3-(4'-hydroxyphenyl)-2-propenyl]piperazine (M-2), benzophenone (M-3) and 1-[4' hydroxyphenyl)-phenylmethyl]-4-(3- phenyl-2-propenyl)piperazine (M-4) has been studied in rat liver microsomes. In Wistar rats, kinetic analysis revealed sex differences (male > female) in the Km values for formation of all the metabolites and the Vmax values for the formation of M-1, M-3 and M-4. The reactions required NADPH, and were inhibited by carbon monoxide and SKF 525-A. Only M-2 formation was suppressed by sparteine or metoprolol, and was significantly lower in female Dark Agouti rats than in Wistar rats of both sexes. The results suggest that CZ is oxidized by cytochrome P450, and M-2 formation is related to debrisoquine/sparteine-type polymorphic drug oxidation. PMID- 1417971 TI - Qualitative differences in [Ca2+]i increases and InsP3 generation following stimulation of N1E-115 cells with micromolar and millimolar ATP. AB - Addition of ATP (100 microM) to populations of the neuronal cell line N1E-115 caused a transient increase in intracellular calcium ([Ca2+]i) which rapidly reached a peak (maximum of 243 +/- 7 nM above basal) and returned to basal after approximately 50 sec. The response was concentration-dependent (EC50 21 +/- 4 microM) and was unchanged when calcium was omitted from the extracellular medium. Transient increases in D-myo-inositol-1,4,5-trisphosphate levels (InsP3) were also observed over a similar time period. Addition of millimolar ATP, however, produced characteristically different responses; [Ca2+]i again increased rapidly (reaching a maximum of 639 +/- 23 nM above basal) but returned to a new maintained plateau (274 +/- 34 nM) which was abolished by the inorganic calcium channel blocker, nickel (1 mM), and omission of calcium from the extracellular medium. InsP3 levels were also maintained but were, however, unaffected by nickel or removal of extracellular calcium. The qualitative difference in the mechanism of calcium elevation produced with millimolar ATP, compared with lower concentrations, suggests that the N1E-115 cells might also contain a low affinity P2 receptor coupled with a calcium channel. PMID- 1417972 TI - Differing response of the glutathione system to fasting in neonatal and adult guinea pigs. AB - Adult, term neonatal and 3 day preterm neonatal guinea pigs were fasted for 48 hr, and the glutathione concentrations of the liver and lung assessed. In adult animals, glutathione concentration decreased by 43% in the liver and 29% in the lung with respect to fed controls. The decrease in liver glutathione was associated with a 75% reduction in the hepatic activity of tau glutamyltranspeptidase (tau GGT). Conversely, both liver and lung glutathione levels in preterm pups remained unchanged following 48 hr food restriction. Likewise, hepatic tau GGT, glutathione reductase (GRed) and glutathione peroxidase (GPx) activities were unchanged by fasting in preterm pups. Fasting increased pulmonary GPx activity by 27% in these pups. In fasted, term animals, substantial increases in both lung (65%) and liver (80%) glutathione concentrations were observed, with concomitant increases in GPx and GRed activities. Hepatic tau GGT activity was significantly reduced (57%) in term pups. These results may suggest that the neonatal guinea pig can maintain tissue glutathione status during periods of nutrient stress, through an increased capacity for recycling oxidized glutathione and a decrease in turnover of the tripeptide. Guinea pig neonates are therefore able to resist starvation-induced decreases in tissue glutathione levels seen in adult rodents. If this is a general neonatal response it may have important clinical implications in the treatment of preterm babies. PMID- 1417970 TI - Glutathione and bile acid synthesis. Effect of GSH content of HepG2 cells on the activity and mRNA levels of cholesterol 7 alpha-hydroxylase. AB - Cholesterol 7 alpha-hydroxylase (CH-7 alpha) activity in HepG2 cells depleted of glutathione (GSH) was reduced significantly (P < 0.05) compared to that in untreated controls. Northern blot analysis of poly A+ mRNA isolated from GSH depleted and control HepG2 cells showed that there was a reduction in mRNA for CH 7 alpha in treated HepG2 cells that was commensurate with the reduction in CH-7 alpha activity. The fact that total RNA, rRNA, and mRNA for beta fibrinogen were unaltered by the depletion of GSH suggests that the change in steady-state CH-7 alpha mRNA content is specifically sensitive to GSH content. This observation represents the first demonstration, for human liver cells, that there is an interaction between GSH levels and the regulation of CH-7 alpha mRNA levels. PMID- 1417974 TI - The reduction of 6-N-hydroxylaminopurine to adenine by xanthine oxidase. AB - The genotoxic and mutagenic compound 6-N-hydroxylaminopurine (HAP) can be detoxified in vitro by enzymatic N-reduction to adenine. This reaction is catalysed by both rat and rabbit liver cytosolic fractions. The formation of adenine was monitored using HPLC. Subcellular distribution of the activity, kinetic parameters and the influence of various cofactors and inhibitors were determined. The N-reduction required NADH or hypoxanthine or xanthine and was strongly inhibited by allopurinol. These observations suggested that the N reductase activity is due to xanthine oxidase (EC 1.2.3.2). Moreover, the involvement of xanthine oxidase is supported by the observation that purified cow milk xanthine oxidase also catalysed this reaction. The N-reduction of HAP was inhibited only weakly by oxygen. In addition, the formation of adenine is catalysed by either the oxidase or dehydrogenase form of xanthine oxidase. Thus, this reaction should be significant for the in vivo detoxification of HAP. PMID- 1417973 TI - Effects of chronic ethanol administration on free radical defence in rat myocardium. AB - Cellular protection against free radical reactions was measured in myocardium from ethanol-fed rats using ethanol administration in drinking water as a model of moderate alcohol intoxication. The activities of Cu,Zn-superoxide dismutase (SOD) and glutathione-S-transferase were higher in ethanol-fed rats than in controls, whereas Mn-SOD, catalase and glutathione peroxidase activities were not altered by ethanol treatment. Myocardial zinc was higher and selenium concentration lower in ethanol-fed rats than in controls. Ethanol consumption, which failed to modify the myocardial vitamin E level, did not result in increased lipid peroxidation, but decreased cytosolic and membraneous protein thiols. PMID- 1417977 TI - Regulation by growth hormone and glucocorticoid of testosterone metabolism in long-term cultures of hepatocytes from male and female rats. AB - The activities of 2-, 6 beta-, 7 alpha- and 16 alpha-testosterone hydroxylase and 5 alpha-testosterone reductase were measured in intact hepatocytes from male and female rats cultured for 8 days in a modified Waymouth medium supplemented with 0.1 or 1.0 microM dexamethasone with or without addition of 1 microgram/mL growth hormone. During culture of hepatocytes from female rats the activity of the male specific 16 alpha-testosterone hydroxylase increased. This increase was significantly inhibited at day 8 by 1 microM dexamethasone as well as by growth hormone. Furthermore, in cultures of hepatocytes from male rats, the activity of the constitutive 16 alpha-testosterone hydroxylase was decreased by 1 microM dexamethasone as well as by growth hormone. The induction of 6 beta-testosterone hydroxylase by dexamethasone was suppressed by growth hormone in hepatocytes from both male and female rats, while the 7 alpha-testosterone hydroxylase activity was unaffected by culture time, hormone additions and gender. The decrease in female-specific 5 alpha-reductase activity with culture time in hepatocytes from female rats was significantly attenuated by growth hormone at 0.1 microM dexamethasone. The effects of growth hormone on testosterone hydroxylase activities in hepatocyte cultures from male and female rats are in accordance with the concept of growth hormone as a "feminization signal". The results suggest that the glucocorticoid-dependent expression of the male constitutive 16 alpha-hydroxylase requires periods of low levels of growth hormone. PMID- 1417976 TI - High-affinity binding of warfarin, salicylate and diazepam to natural mutants of human serum albumin modified in the C-terminal end. AB - High-affinity binding of warfarin, salicylate and diazepam to four natural mutants of human serum albumin was studied by equilibrium dialysis at pH 7.4. The mutants Alb Milano Fast and Alb Vanves possess single amino acid substitutions close to the C-terminus, namely 573 Lys-->Glu and 574 Lys-->Asn, respectively. By contrast, Alb Catania and Alb Venezia are chain termination mutants in which several amino acids have been changed or deleted. Binding of warfarin to the variants was lower than binding to normal (wild-type) albumin (Alb A). The association constants were 73% (Alb Milano Fast, Alb Vanves and Alb Catania) or 67% (Alb Venezia) of that determined for Alb A. The results obtained with salicylate were more dependent on the type of mutation. The constants were either comparable to the normal value (Alb Catania) or reduced to 64% (Alb Milano Fast), 71% (Alb Vanves) or 43% (Alb Venezia) of that value. Diazepam binding to the variants was normal, except for binding to Alb Venezia in which case the association constant was reduced to 76% of that calculated for Alb A. The results are in accordance with the view that warfarin, salicylate and diazepam bind to three different high-affinity sites. It is proposed that the sites for warfarin and salicylate are situated rather close to each other in domain II, and that these high-affinity sites are relatively susceptible to conformational changes of the protein. By contrast, the primary diazepam site is placed closer to, or within, domain III of albumin and seems to be less affected by conformational changes in the protein molecule. PMID- 1417978 TI - Plasma membrane as a site of redox activation of daunomycin in intact human erythrocytes. Quantitative evaluation of the hydrogen peroxide produced by the membrane with respect to the cytosol. AB - The relative importance in human red blood cells of the plasma membrane as a site of redox activation of anthracyclines as compared to hemoglobin was evaluated by assaying the H2O2 produced upon exposure to daunomycin. The method of H2O2 dependent irreversible inhibition of catalase (EC 1.11.1.6) activity by 3-amino 1,2,4-triazole was applied to intact erythrocytes, as well as to isolated membranes with added purified catalase. The results obtained indicate a secondary role in daunomycin activation for the plasma membrane from a quantitative point of view, although membrane pathways can be more harmful than cytosolic pathways, especially towards extracellular targets, when the high efficiency of the cytosolic antioxidative defences and the external location of the membrane activation site are considered. PMID- 1417975 TI - Phenothiazines inhibit acetylcholinesterase by concentration-dependent-type kinetics. A study with trifluoperazine and perphenazine. AB - The properties of perphenazine (PPZ) and trifluoperazine (TFP) as fluorescent dyes were exploited to calculate their critical micellar concentrations. The relative fluorescence quantum yield of the two amphiphiles was dependent on their concentration, abruptly decreasing above 30-40 microM PPZ and 20-30 microM TFP. Evidence is presented that this phenomenon is driven by the formation of non fluorescent drug aggregates. The type of inhibition kinetics displayed by PPZ and TFP on human erythrocyte acetylcholinesterase (AChE) was also dependent on drug concentration, turning from non-competitive to a "mixed" inhibition type at concentrations at which PPZ and TFP were demonstrated to undergo micelle formation. Results support the notion that phenothiazines may interact with AChE both as monomers and micellar aggregates, producing different inhibitory effects. PMID- 1417979 TI - Interaction of berbamine compound E6 and calmodulin-dependent myosin light chain kinase. AB - The interaction of the berbamine compound E6 and calmodulin (CaM)-dependent myosin light chain kinase (MLCK) has been studied. The experimental results showed that the inhibition of MLCK activity was increased with increasing amounts of E6 and was overcome completely by the addition of excessive CaM. The stimulatory activity of MLCK induced by CaM was gradually inhibited by the increasing concentrations of compound E6, showing that the inhibition of MLCK activity by compound E6 was concentration dependent; and the Ki was 0.95 microM. Compound E6 diminished the fluorescence intensity of dansyl-labeled CaM and the intensity was increased gradually by the addition of different amounts of CaM. Compound E6 had no effect on the activity of MLCK fragments produced by limited trypsinization, and it is a novel and considerably potent calmodulin antagonist. PMID- 1417980 TI - Multiple effects of staurosporine, a kinase inhibitor, on thymocyte functions. Comparison with the effect of tyrosine kinase inhibitors. AB - The effects of staurosporine, a protein kinase inhibitor, on the signal transduction and proliferation of thymocytes were studied. Signal transduction in response to Concanavalin A (Con A) as well as Concanavalin A (Con A)-induced augmentation of [3H]inositol incorporation into phospholipids were inhibited by staurosporine (> or = 10(-8) M). Staurosporine inhibited thymocyte proliferation in response to Con A in the presence or absence of the phorbol ester, phorbol myristate acetate (TPA) (10 nM). This inhibition was observed regardless of whether staurosporine was added together with Con A or 3 hr later. High concentrations of staurosporine (> 10(-8) M) inhibited thymocyte proliferation induced by the calcium ionophore A23187 and the phorbol ester TPA, whereas lower concentrations of the inhibitor (< or = 10(-8) M) enhanced thymidine incorporation in response to these activators. This dual effect of staurosporine was also observed in the presence of the staurosporine-related kinase inhibitor, K252a. In contrast, the tyrosine kinase inhibitor, tyrphostin AG490, inhibited the response to A23187 and TPA at all concentrations of the inhibitor and no augmentation was seen. Interleukin 2 (IL-2)-driven mitogenesis in IL-2-dependent cells was also inhibited by staurosporine. We suggest that the inhibition of thymocyte proliferation by staurosporine results from inhibition of both protein kinase C and tyrosine kinase: the augmentation of the response to A23187 and TPA results from inhibition of protein kinase C. Inhibition of signal transduction as well as inhibition of IL-2-driven mitogenesis result from inhibition of tyrosine kinase. PMID- 1417982 TI - Effects of chemical modification of nitrobenzylthioinosine on its binding to high affinity membrane binding sites and inhibition of nucleoside transport. AB - Nitrobenzylthioinosine (NBTI) was systematically modified by attachment of substituents at the 2-, 5'-, 3'- and 2'-positions in order to assess the importance of these positions in the binding of NBTI to high-affinity membrane binding sites (Kd < or = 1 nM) and the inhibition of NBTI-sensitive, equilibrative nucleoside transport by mammalian cells. We determined the effect of the derivatives on the equilibrium binding of 1 nM [3H]NBTI to human erythrocytes and mouse P388 leukemia cells and on the inhibition of zero-trans influx of formycin B in P388 cells and equilibrium exchange of uridine in human erythrocytes. Placement of substituent groups at the 5'-position of NBTI had relatively little effect on its binding to high-affinity binding sites or its inhibition of nucleoside transport, regardless of the size of the substituent group (up to about 1000 kDa). All substituents at the 2-position considerably reduced the affinity of NBTI to membrane binding sites and its potency as an inhibitor of nucleoside transport, but some substituent groups reduced the affinity of binding more than the inhibition of nucleoside transport. The effect of the 2-substituents was not directly related to their size. Attachment of a succinate at the 3'- or 5'-position also reduced to a greater extent the binding of NBTI than its inhibition of nucleoside transport, which was relatively little affected. Attachment of succinates at both the 3' and 5'-positions almost completely abolished both binding to high-affinity sites and inhibition of nucleoside transport. Both functions of NBTI were abolished completely by the simultaneous blockage of the 2'- and 3'-positions. None of the NBTI derivatives significantly inhibited NBTI-resistant equilibrative formycin B transport in P388 and Novikoff rat hepatoma cells at concentrations of < or = 1 microM. PMID- 1417983 TI - Inhibitory effect of an intracellular glutathione on delta 12-prostaglandin J2 induced protein syntheses in porcine aortic endothelial cells. AB - Delta 12-Prostaglandin (PG) J2 caused porcine aortic endothelial cells to synthesize a 31,000-dalton heme oxygenase and a 67,000-dalton protein (p67). Treatment of the cells with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, depleted intracellular GSH, and enhanced the induction of heme oxygenase and p67 syntheses by delta 12-PGJ2. In contrast, treatment with GSH increased the intracellular GSH level and reduced the induction. There was a reciprocal relationship between the level of intracellular GSH, and that of the induction of heme oxygenase and p67 syntheses by delta 12 PGJ2. An increase in the intracellular GSH level caused an increase in the ethyl acetate-unextractable form of delta 12-PGJ2 in the cytosol, but suppressed the accumulation of delta 12-PGJ2 in the nuclei. Furthermore, GSH strongly inhibited the in vitro binding of delta 12-PGJ2 to isolated nuclei, which is N ethylmaleimide sensitive. Moreover, the induction of heme oxygenase and p67 syntheses by the thiol-reactive agents arsenite and diethylmaleate was also inhibited by GSH treatment and enhanced by BSO treatment. These results demonstrate that intracellular GSH suppresses delta 12-PGJ2-induced heme oxygenase and p67 syntheses by inhibiting the binding of delta 12-PGJ2 to nuclei. PMID- 1417981 TI - Inhibition of EGR-1 and NF-kappa B gene expression by dexamethasone during phorbol ester-induced human monocytic differentiation. AB - The treatment of human myeloid leukemia cells (HL-60, U-937, THP-1) with 12-O tetradecanoylphorbol-13-acetate (TPA) is associated with growth arrest and appearance of a differentiated monocytic phenotype. While previous studies have reported that the glucocorticoid dexamethasone blocks phenotypic characteristics of monocytic differentiation, we demonstrated in the present work that dexamethasone delays the effects of TPA on the loss of U-937 cell proliferation. We also demonstrated that this glucocorticoid inhibits TPA-induced increases in expression of the EGR-1 early response gene. The results of nuclear run-on assays and half-life experiments indicated that this effect of dexamethasone is regulated at the post-transcriptional level. Similar studies were performed for the NF-kappa B gene. While TPA treatment was associated with transient increases in NF-kappa B mRNA levels, this induction was blocked by dexamethasone. In contrast, dexamethasone had no significant effect on the activation of pre existing NF-kappa B protein as determined in DNA-binding assays. Taken together, these findings suggest that the activated glucocorticoid receptor inhibits signaling pathways which include expression of the EGR-1 and NF-kappa B genes and that such effects may contribute to a block in TPA-induced monocytic differentiation. PMID- 1417986 TI - Induction of a pleiotropic response by phenobarbital and related compounds. Response in various inbred strains of rats, response in various species and the induction of aldehyde dehydrogenase in Copenhagen rats. AB - The ability of phenobarbital (PB) to induce a "pleiotropic response" which includes both cytochromes P450 (CYP) as well as other drug-metabolizing enzymes was investigated in mice, rabbits, hamsters, and various inbred strains of rats. PB induced similar drug-metabolizing enzymes (CYP2B, CYP3A, and epoxide hydrolase) in rats, mice, rabbits and hamsters. PB and two structural analogues (ethylphenylhydantoin and barbital) induced a variety of drug-metabolizing enzymes (CYP2B, CYP3A, CYP2A, epoxide hydrolase) in a series of inbred strains of rats. In contrast, levels of aldehyde dehydrogenase (ALDH) (propionaldehyde, NAD+) which were expressed constitutively in all strains of rats were induced by PB in only two of the eight strains (ACI, Copenhagen). Further investigations of ALDH induction by structurally diverse compounds in Copenhagen rats demonstrated a strong correlation between the induction of ALDH and other elements of the pleiotropic response (CYP2B, CYP3A, epoxide hydrolase). These results imply that induction of ALDH (propionaldehyde, NAD+) is associated with the PB pleiotropic response in Copenhagen rats. PMID- 1417985 TI - Dihydrolipoic acid--a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. AB - Thioctic (lipoic) acid is used as a therapeutic agent in a variety of diseases in which enhanced free radical peroxidation of membrane phospholipids has been shown to be a characteristic feature. It was suggested that the antioxidant properties of thioctic acid and its reduced form, dihydrolipoic acid, are at least in part responsible for the therapeutic potential. The reported results on the antioxidant efficiency of thioctic and dihydrolipoic acids obtained in oxidation models with complex multicomponent initiation systems are controversial. In the present work we used relatively simple oxidation systems to study the antioxidant effects of dihydrolipoic and thioctic acids based on their interactions with: (1) peroxyl radicals which are essential for the initiation of lipid peroxidation, (2) chromanoxyl radicals of vitamin E, and (3) ascorbyl radicals of vitamin C, the two major lipid- and water-soluble antioxidants, respectively. We demonstrated that: (1) dihydrolipoic acid (but not thioctic acid) was an efficient direct scavenger of peroxyl radicals generated in the aqueous phase by the water-soluble azoinitiator 2,2'-azobis(2-amidinopropane)-dihydrochloride, and in liposomes or in microsomal membranes by the lipid-soluble azoinitiator 2,2' azobis(2,4-dimethylvaleronitrile); (2) both dihydrolipoic acid and thioctic acid did not interact directly with chromanoxyl radicals of vitamin E (or its synthetic homologues) generated in liposomes or in the membranes by three different ways: UV-irradiation, peroxyl radicals of 2,2'-azobis(2,4 dimethylvaleronitrile), or peroxyl radicals of linolenic acid formed by the lipoxygenase-catalyzed oxidation; and (3) dihydrolipoic acid (but not thioctic acid) reduced ascorbyl radicals (and dehydroascorbate) generated in the course of ascorbate oxidation by chromanoxyl radicals. This interaction resulted in ascorbate-mediated dihydrolipoic acid-dependent reduction of the vitamin E chromanoxyl radicals, i.e. vitamin E recycling. We conclude that dihydrolipoic acid may act as a strong direct chain-breaking antioxidant and may enhance the antioxidant potency of other antioxidants (ascorbate and vitamin E) in both the aqueous and the hydrophobic membraneous phases. PMID- 1417987 TI - Nonenzymic glycation of albumin by acyl glucuronides in vitro. Comparison of reactions with reducing sugars. AB - Acyl glucuronides are ubiquitous metabolites formed from acidic xenobiotics and endogenous compounds, such as bilirubin. Previous studies indicated that the covalent binding of acyl glucuronides to proteins occurs via an imine intermediate in a manner analogous to the glycation of proteins via reducing sugars. When glucuronic acid was incubated in solution with albumin, it formed 10 and 4 times more fluorescent, Maillard reaction products with albumin after 25 days than did glucose or fructose, respectively. However, radiolabeled glucuronic acid exhibited less covalent binding to albumin than either glucose or fructose. Circular dichroism measurements indicate that glucuronic acid is about 0.02% open chain form with exposure of the reactive aldehyde, whereas fructose and glucose have 2 and 0.0026% present in solution as the open chain; thus, differences in reactivity of the reducing sugars were not correlated with exposure of the free aldehyde. Methyl glucuronate formed little fluorescent product with albumin, suggesting that the C-6 carboxylate of glucuronic acid may facilitate the reactions after covalent binding that lead to the formation of fluorescent products. When acyl glucuronide metabolites of two previously marketed acidic drugs, zomepirac and suprofen, were incubated with albumin at a concentration of 2.5 mM, more fluorescent product was formed than by 500 mM glucose. Reversible binding of the acyl glucuronides to albumin was 60-90%, but almost zero for the free reducing sugars, which indicates that reversible binding may explain the enhanced reactivity of the acyl glucuronides in forming fluorescent products with albumin. These results indicate that acyl glucuronides are reactive metabolites that may cause significant glycation of proteins with glucuronic acid in vivo. PMID- 1417984 TI - Contributory role of lung pleura to release of anaphylactic mediators from guinea pig lung in response to ovalbumin or A23187. AB - Previous findings revealed greater contractile responses of guinea pig lung pleural surface strips to antigen or A23187 challenge than denuded lung parenchymal strips (lung strip devoid of any pleura). Moreover, we have identified a high density of mast cells distributed throughout the lung pleura. The present study examined mediators released from guinea pig lung pleural surface and denuded lung parenchyma fragments in response to immunologic challenge with ovalbumin (OA) or non-immunologic challenge with the ionophore A23187. Histamine levels were measured radioenzymatically; leukotrienes (LTs), prostaglandins (PGs) and thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), were quantitated using an enzyme immunoassay. Histamine release reached a maximal level 3-5 min after OA challenge, whereas A23187 induced histamine release increased gradually in a time-dependent manner. Similar kinetics were observed in the release of LTs, PGs and TXA2. Pleural surface released a substantially (P < 0.05) greater amount of histamine to both challenges than denuded parenchyma. Moreover, histamine content in pleural surface was significantly (P < 0.05) higher than in denuded parenchyma. Pleural surface also released considerably (P < 0.05) more LTB4, LTC4, and LTE4 in response to OA and A23187 than denuded parenchyma. In contrast, pleural surface and denuded parenchyma released equivalent amounts of PGD2, PGE2, PGF2 alpha, and TXA2 in response to both challenges. The rank order of leukotriene release was LTC4 > LTE4 > LTB4, whereas that of prostanoid release was TXA2 >> PGD2 > or = PGF2 alpha >> PGE2. We conclude that pleural surface is the major source of histamine and leukotrienes released from guinea pig lung in vitro in response to OA and A23187, whereas both pleural surface and denuded parenchyma participate to the same extent in prostaglandin and TXA2 production after such challenges. PMID- 1417988 TI - Effects of interleukin 1 alpha on the activities and gene expressions of the cytochrome P450IID subfamily. AB - The mechanism by which recombinant human interleukin 1 alpha (rhIL-1 alpha) inhibits the activities of drug-metabolizing enzymes of rat liver microsomes, especially debrisoquine monooxygenase and bufuralol monooxygenase (both cytochrome P450IID supported reactions), as well as other enzymes, was investigated by injecting IL-1 alpha into rats. rhIL-1 alpha suppressed the activities of various P450-linked monooxygenase systems such as aminopyrine N demethylase, benzphetamine N-demethylase, and 7-ethoxycoumarin O-deethylase. It also suppressed the activities of debrisoquine monooxygenase and bufuralol monooxygenase. On the other hand, IL-1 alpha had little effect on the activity of p-nitroanisole N-demethylase. The suppression of debrisoquine monooxygenase and bufuralol monooxygenase activities was caused by a decrease in the amounts of immunoreactive P450IID protein and its mRNA. The reduction rates in the level of immunoreactive P450IID protein and its mRNA were comparable. These results suggest that at the mRNA level, the enzymatic activities of debrisoquine monooxygenase and bufuralol monooxygenase are down-regulated by IL-1 alpha. PMID- 1417990 TI - [p26--a calcium binding protein from photoreceptor cells in the bovine retina: primary structure and expression in E. coli]. AB - The primary structure of the bovine retinal calcium binding protein P26 has been determined by the parallel analysis of the protein and the corresponding cDNA. This protein is identical to recovering and shares 59% homology with visinin, a cone specific calcium binding protein from chicken retina. P26 was expressed in E. coli as a fusion protein and, after purification by affinity chromatography on IgG-Sepharose 6, cleaved off with enteropeptidase. PMID- 1417989 TI - Effect of lysosomotropic agents on the taurocholate-stimulated biliary excretion of horseradish peroxidase. AB - The effects of the lysosomotropic agents chloroquine and leupeptin on the taurocholate-stimulated biliary excretion of horseradish peroxidase (HRP) was studied in bile fistula rats. HRP (0.5 mg/100 g body wt) was injected into the portal vein during taurocholate (0.4 mumol/min/100 g body wt) or saline infusion. HRP appeared in bile showing both an early (approx. 5 min) and a late (approx. 25 min) excretion peak. The late peak, which represented about 95% of the total HRP excreted, is due to transcellular vesicular transport. The early peak is mainly due to paracellular leakage although a rapid vesicular transport also contributes. Taurocholate infusion significantly increased the biliary output of HRP (both peaks) and of the endogenous lysosomal enzyme acid phosphatase. Pretreatment with chloroquine or leupeptin inhibited the taurocholate-stimulated late excretion of HRP into bile, without affecting its early excretion. The lysosomotropic agents did not affect the biliary excretion of bile salts but significantly inhibited the taurocholate-stimulated biliary excretion of acid phosphatase. The results are consistent with a role of lysosomes in the taurocholate-stimulated major transcellular vesicular transport of HRP into bile. PMID- 1417991 TI - [Sequence-specific modification of nucleic acids by oligonucleotide derivative containing alkylating groups in the C-5-position of deoxyuridine]. AB - A new type of alkylating derivatives of oligonucleotides with 4(N-methyl-N-2 chloroethylamino)benzyl (RCl) group at C-5 of deoxyuridine with a high extent of the target modification was prepared. The synthesized reagents d(ULNHRClCCACTT), where L = CH2 (Ia), CH2OCH2CH2 (Ib) and CH2NHCOCH2CH2 (Ic), proved to effectively (80-90%) modify the oligonucleotide d(TAAGTGGAGTTTGGC). The reagents (Ia) and (Ib) alkylate G6, G7 and G9 positions, while the reagent (Ic) modifies predominantly G9. PMID- 1417992 TI - [Synthesis of an artificial gene coding for thymosin alpha1 and its expression in Escherichia coli as a hybrid with human tumor necrosis factor]. AB - Chemical-enzymatic synthesis and cloning in Escherichia coli of an artificial gene encoding the immunoactive peptide thymosin alpha 1 have been carried out. Recombinant plasmids were constructed which contain fusion genes coding for hybrids of human tumour necrosis factor (TNF) and thymosin alpha 1 as N- or C terminal part of the hybrid protein. In the C-terminal hybrid protein, TNF and thymosin alpha 1 are linked through a methionine residue, thus allowing for thymosin alpha 1 to be cleaved off the rest of the hybrid protein with cyanogen bromide. In case of the N-terminal hybrid protein, the linker between the thymosin alpha 1 and TNF sequences is the acid-labile dipeptide Asp-Pro. Expression of the hybrid genes in E. coli and properties of the recombinant proteins were studied. The N-terminal hybrid protein was secreted into periplasmic space, in contrast with the C-terminal hybrid protein, which formed insoluble aggregates inside bacterial cells. Procedures for the isolation of both hybrid proteins were developed. The N-terminal hybrid protein displayed full biological activity in the cytotoxic assay on the mouse fibroblast L-929 whereas the C-terminal hybrid protein proved to be much less active. Treatment of the hybrid protein TNF-thymosin alpha 1 with cyanogen bromide lead to a mixture of two polypeptides, from which thymosin alpha 1 was purified to homogeneity by simple chromatographic procedures. PMID- 1417993 TI - [Expression of a synthetic gene for human interleukin-4 in E. coli cells. Preparation of a biologically active protein]. AB - Expression E. coli plasmid were constructed in which the human interleukin-4 (hIL4) synthetic gene is controlled by tac promoter. The expression level of the gene depends on the distance between RBS and the initial codon ATG, with the maximal production in case of the nine base pair distance. The recombinant protein, accumulated in the inclusion bodies, was solubilized, renaturated, and purified to homogeneous, biologically active preparation, the yield being 2 mg/g wet cells. PMID- 1417994 TI - [Synthesis of protected fragments of the capsular polysaccharide of Streptococcus pneumoniae, type 8]. AB - Oxidation of acetates of allyl and 2-(benzyloxycarbonylamino)ethyl beta cellobiosides (with OH-4' and OH-6' unprotected) with the Jones reagent followed by esterification (with diazomethane or phenyldiazomethane) gave corresponding uronates with OH-4' unsubstituted. Condensation of these glycosyl acceptors and benzylated derivatives of D-galactose or 4-O-(alpha-D-glucopyranosyl)-D-galactose led to the protected tri- and tetrasaccharide fragments of the capsular polysaccharide from Streptococcus pneumoniae type 8. PMID- 1417995 TI - [Synthesis of oligodeoxyribonucleotides containing 5-fluoro-2' deoxyribocytidine]. AB - A synthesis of the phosphoroamidite derivative of 5-fluoro-2'-deoxycytidine which allows one to introduce the modified nucleoside residue into the 5'-position of the oligodeoxyribonucleotide by the standard solid phase phosphoroamidite method, has been carried out. Oligonucleotides with 5-fluoro-2'-deoxycytidine residues in various positions of the DNA strand are obtained by the combination of chemical and enzymatic syntheses. PMID- 1417996 TI - [Folding of peptide chains during formation of the spatial structure of protein molecules is determined by the code of amino acid codon roots]. AB - Basing on the analysis of a large number of protein sequences (Cserzo M., Simon I., 1989), the structure of the amino acid nearest neighbour pair whose occurrence has a maximal positive deviation from the mean statistical value, is shown to correspond in most cases to the code of the amino acid codon roots. It reveals particularly amino acid pairs in n and n+5 positions of polypeptide chains. Amino acids belonging to A/U family contribute mostly to the folding of peptide chains. PMID- 1417997 TI - [Secretion of recombinant human epidermal growth factor into the periplasm in Escherichia coli cells]. AB - Secretion vectors were constructed in which a synthetic gene of human epidermal growth factor (hEGF) joined with a gene coding for the leader peptide to one of the E. coli outer membrane major proteins (OmpF) is controlled by tac promoter. The increase of the hEGF yield was achieved by the multiplication of the gene copies. The hEGF in bacterial cells was secreted into periplasm. The recombinant protein was isolated by means of reverse phase chromatography as almost homogenous preparation (greater than 98%), the yield being 7 mg/l bacterial culture. The sequence of twenty-five N-terminal amino acid residues of the isolated hEGF coincided with that of the natural protein. The preparation proved to be biologically active. PMID- 1417998 TI - [Structure of macrocyclic K+, Rb+-complexon of meso-valinomycin monohydrate, cyclo[-(D-Val-Hyi-Val-D-Hyi)3-].H2O, in a crystalline complex with dioxane by x ray structural data]. AB - The crystal structure of a valinomycin analogue, cyclo[-(D-Val-Hyi-Val-D-Hyi)3 ]x(C60H102N6O18) crystallized with dioxane and water molecules, has been solved by X-ray direct methods. The conformation found is analogous to one established for free meso-valinomycin crystallized from other organic solvents. It is characterized by a centrosymmetric bracelet form, stabilized by six intramolecular 4----1 type hydrogen bonds between amide N-H and C = O groups. One water molecule is fixed asymmetrically by hydrogen bonds in the internal negatively charged cavity of the complexon. The meso-valinomycin molecule "bracelets" in the crystal form stacks alternatively with dioxane molecules. PMID- 1417999 TI - [Substituted 6-aminonaphthalene-1-sulfamides as fluorogenic indicators groups for synthetic proteinase substrates]. AB - Alkyl substituted 6-aminonaphthalene-1-sulphamides (ANSA), hydrobromides of substituted 6-(N alpha-benzyloxycarbonyl-L-arginyl)aminonaphthalene-1-sulphamides (Z-Arg-ANSA) and hydrobromides of 6-(benzyloxycarbonylglycylglycyl-L- arginyl)aminonaphthalene-1-sulphamides (Z-Gly-Gly-Arg-ANSA) are synthesized and their absorption and emission spectra measured. ANSA have an emission band at 470 480 nm, comparable or exceeding in intensity that of compounds used as fluorogenic leaving groups in peptide cleavage reactions. The bands of Z-Arg-ANSA and Z-Gly-Gly-Arg-ANSA are shifted to the short-wave side and do not overlap with ANSA's emission band. Reactions of Z-Arg-ANSA and Z-Gly-Gly-Arg-ANSA with trypsin were studied. The kinetic parameters (kcat and Km) of the reaction of Z-Arg-ANSA were found to depend on the nature and the number of substituents in the sulphamide. In the case of Z-Gly-Gly-Arg-ANSA, this dependence is negligible and kcat/Km exceeds by over ten times this parameter of Z-Arg-ANSA. ANSA can apparently be used in the synthesis of fluorogenic substrates of proteases. PMID- 1418000 TI - [Synthesis of phosphono analogs of a phospholipid platelet activating factor]. AB - Structural analogues of phospholipidic platelet activating factor, (2-acetoxy-3 octadecyloxy)propyl-1-phosphonocholine and (2-methoxy-3-octadecyloxy)propyl-1 phosphonocholine, were synthesized. High efficiency of the polymer-bound dibenzo 18-crown-6-ether as the O-alkylation catalyst was demonstrated. Reaction of allyl octadecyl ether with methanol and iodine in the presence of zinc oxide was shown to give a mixture of 1-iodo-2-methoxy- and 1-methoxy-2-iodoprop-3-yl ethers of octadecanol in the 3:1 ratio. PMID- 1418001 TI - [Study of the amino acid sequence of latroinsectotoxin from black widow spider venom]. AB - The N-terminal amino acid sequence of alpha-latroinsectotoxin from the venom of Latrodectus mactans tredecimguttatus was determined. Then the toxin was digested by trypsin and total or partial amino acid sequences of twenty-six tryptic peptides were established. This resulted in the structural information needed for the construction of probes followed by the cloning of the alpha-latroinsectotoxin structural gene. PMID- 1418002 TI - Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain. AB - OBJECTIVE: Fibromyalgia is a common syndrome of musculoskeletal pain and fatigue. Lacking distinctive tissue or laboratory correlations, it has often been considered a form of "psychogenic rheumatism." In the present study, the notion that the stage-4 sleep anomaly typically seen in the fibromyalgia syndrome may disrupt growth hormone secretion was tested. Because growth hormone has a very short half-life, serum levels of somatomedin C were measured; somatomedin C is the major mediator of growth hormone's anabolic actions and is a prerequisite for normal muscle homeostasis. METHODS: Serum levels of somatomedin C were measured in 70 female fibromyalgia patients and 55 healthy controls, using a peptide specific radioimmunoassay. RESULTS: Significantly lower levels of somatomedin C were observed in the fibromyalgia patients compared with controls (mean +/- SD 124.7 +/- 47 ng/ml versus 175.2 +/- 60 ng/ml; P = 0.000001). These results could not be explained by concomitant therapy or by weight, and in a subset of 21 patients in whom this was investigated, there was no correlation with various indices of disease activity. CONCLUSION: These findings indicate that there is a distinctive disruption of the growth hormone-somatomedin C neuroendocrine axis in a majority of fibromyalgia patients. It is hypothesized that this abnormality may explain the link between disturbed sleep and predisposition to muscle pain. PMID- 1418003 TI - High-dose immunoglobulin therapy as an immunomodulatory treatment of rheumatoid arthritis. AB - OBJECTIVE: To investigate the efficacy of high-dose intravenous immunoglobulin (IVIg) in the treatment of refractory rheumatoid arthritis (RA). METHODS: Ten patients with active, severe RA that was unresponsive to first- and second-line agents were administered IVIg monthly, for 6 months. RESULTS: Following IVIg treatment, there was significant improvement in both subjective and objective parameters of disease activity in all 9 patients who completed the protocol. This improvement was noted to occur as early as after the second infusion of IVIg. After discontinuation of the treatment, all patients had a relapse of the disease within a few weeks. CONCLUSION: Since the reduction in clinical activity paralleled a decrease in the CD4+CDw29+:CD4+CD45RA+ cell ratio, some of the therapeutic benefits associated with IVIg may be due to a direct influence on the CD4+CD45RA+ subset. Although the possibility of carrying out further controlled studies on a larger scale is limited by the high cost of the treatment, IVIg appears to be an effective therapy for refractory RA. PMID- 1418004 TI - Treatment of systemic sclerosis with recombinant interferon-gamma. A phase I/II clinical trial. AB - OBJECTIVE: A phase I/II trial to examine the safety and efficacy of interferon gamma (IFN gamma) therapy for patients with systemic sclerosis (SSc). METHODS: An 18-week open-label study was performed. Eighteen patients with rapidly progressive SSc were enrolled, 14 of whom completed at least 16 weeks of the study. These 14 patients had a mean age of 40 years and had been diagnosed as having SSc an average of 10.1 months prior to study entry. Recombinant IFN gamma was injected intramuscularly 3 times weekly for 18 weeks. Six patients received a 0.1 mg/m2 dose, while 8 patients received a 0.5 mg/m2 dose. Patients who completed the 18-week trial were offered maintenance therapy at a dose of up to 0.5 mg/m2. The effects of IFN gamma on skin involvement were assessed by 2 methods: 1) evaluation of skin thickness, by scoring 15 zones according to a 0 (normal skin) to 3 (hidebound skin) scale; and 2) determination of the total body surface area involved, by using 2-dimensional body diagrams to indicate areas affected, and then having a second, "blinded," assessor calculate the area score with a planimeter. RESULTS: The mean skin thickness score decreased from a baseline of 25.9 to 19.1 (P < 0.03), and the mean area scores declined from 33.1 to 19.6 (P < 0.02) after 18 weeks of IFN gamma treatment. Ten patients had a > 25% decrease in area score. Five patients had a > or = 70% decrease in area score, and 3 of them have not experienced disease recurrence for 6 to 17 months after discontinuation of IFN gamma. Five patients withdrew before the study ended. Three of these patients developed renal crisis, which may reflect the severity of the SSc in the study group, although an adverse effect of IFN gamma in SSc cannot be excluded. CONCLUSION: IFN gamma was associated with a beneficial effect on the skin involvement in most of this series of patients with rapidly progressive SSc. A placebo-controlled study will be necessary to confirm these results. PMID- 1418005 TI - Methotrexate treatment of recalcitrant childhood dermatomyositis. AB - OBJECTIVE: To review the clinical course of 16 children with recalcitrant dermatomyositis (DM), who were treated with oral methotrexate (MTX) in addition to prednisone. METHODS: Sixteen patients with recalcitrant DM who were treated with MTX in addition to prednisone were followed between 1984 and 1990. The patients' clinical responses to treatment, including alterations in muscle strength and muscle enzyme levels, changes in prednisone dosage, and development of toxicity or complications were reviewed retrospectively. RESULTS: All 12 patients who received MTX for at least 8 months regained normal muscle strength. In 11 of the 12, the prednisone dosage could eventually be tapered to < or = 5 mg/day. Complications during MTX treatment required discontinuation of MTX in 5 patients, and were unrelated to the cumulative dose of the drug. Active disease recurred in 5 patients in whom MTX had been discontinued after apparent clinical remission had been achieved. CONCLUSION: MTX, in combination with prednisone, is a useful adjunct in the treatment of recalcitrant childhood DM. However, recurrence of disease after withdrawal of MTX suggests that the drug may have a suppressive, rather than a remittive, effect. PMID- 1418006 TI - Effects of interleukin-6 on the metabolism of connective tissue components in rheumatoid synovial fibroblasts. AB - OBJECTIVE: High levels of interleukin-6 (IL-6) have been found in the synovial fluid of patients with rheumatoid arthritis (RA). We undertook the present study to investigate the role of IL-6 in this disease. METHODS: We examined the effects of IL-6, in comparison with IL-1, on the biosynthesis of extracellular matrix macromolecules and of matrix-degrading proteinases in rheumatoid synovial fibroblasts. RESULTS: In rheumatoid synovial fibroblasts, IL-6 by itself enhanced the production of plasminogen activator, its inhibitor, and tissue inhibitor of metalloproteinases, whereas it did not modulate the biosynthesis of precursor of matrix metalloproteinase 1 (proMMP-1) (tissue collagenase), proMMP-3 (stromelysin), or connective tissue components. However, IL-1-induced production of proMMP-1 and proMMP-3 was preferentially augmented by IL-6. CONCLUSION: These results suggest that in RA, IL-6 may participate along with IL-1 in fine tuning of the catabolism of connective tissue components, by modulating the balance between connective tissue-degrading enzymes and their inhibitors. PMID- 1418007 TI - Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations. AB - OBJECTIVE: The inflammatory myopathies are characterized by distinctive autoantibodies that are associated with certain clinical features and immunogenetic patterns. Anti-PM-Scl is one such antibody and is found in pure myositis, myositis in overlap, and systemic sclerosis (SSc). Our purpose was to describe the clinical and immunogenetic associations of the anti-PM-Scl antibody. METHODS: Serum samples from 617 patients with various connective tissue diseases were screened for anti-PM-Scl antibody by indirect immunofluorescence and Ouchterlony double immunodiffusion. Patients with anti-PM-Scl were serologically typed for HLA-DR and DQ, and the genes encoding DQ alpha and DQ beta were characterized by hybridization of sequence-specific oligonucleotide to amplified genomic DNA. RESULTS: Twenty-three patients (4%) had serum anti-PM-Scl. Sixteen had either pure myositis or myositis in overlap, 6 had SSc alone, and 1 had SSc and rheumatoid arthritis. Twenty of the antibody-positive patients had serologic HLA typing performed; 15 (75%) were HLA-DR3 positive, and 17 (85%) expressed the DQw2 allele. None of the 5 DR3 negative patients shared a unique DR or DQ antigen with the DR3 positive patients, and further DNA analysis of 10 patients (4 of whom were DR3 negative) did not reveal any unique DQ alleles. CONCLUSION: Anti-PM Scl identifies a subset of patients with myositis, SSc, or an overlap of the two disorders, and this antibody has a strong but not exclusive immunogenetic association with the HLA-DR3 antigen. PMID- 1418009 TI - Radiologic vignette. Osseous syphilis. PMID- 1418008 TI - In vivo expression of stromelysin in synovium and cartilage of rabbits injected intraarticularly with interleukin-1 beta. AB - OBJECTIVE: To examine the in vivo expression of the matrix metalloproteinase stromelysin in the synovium and articular cartilage of rabbits injected intraarticularly with recombinant human interleukin-1 beta (IL-1). METHODS: The direct isolation of messenger RNA (mRNA) from articular cartilage without the prior isolation of chondrocytes is described. The in vivo expression of stromelysin was examined at the mRNA level by Northern blot analysis, and at the protein level by in situ immunolocalization and by enzyme-linked immunosorbent assay. RESULTS: In the synovium of IL-1-injected joints, stromelysin mRNA levels were highest at 4 hours and declined to background levels within 24 hours. In the cartilage of IL-1-injected joints, stromelysin mRNA was elevated at 4 hours and continued to increase until 8 hours, before declining. Stromelysin mRNA expression preceded a similar increase in stromelysin protein levels in both synovium and cartilage. CONCLUSION: Intraarticular injection of IL-1 induced the endogenous expression of stromelysin mRNA and protein in both synovium and cartilage. The kinetics of stromelysin expression correlated well with the accumulation of stromelysin and proteoglycan in synovial fluids. Therefore, the de novo synthesis of stromelysin in cartilage may have contributed to the loss of proteoglycan from that tissue. PMID- 1418010 TI - Retroperitoneal fibrosis associated with aortitis. PMID- 1418011 TI - Does methotrexate retard radiologic progression of rheumatoid arthritis? PMID- 1418012 TI - Giant cell arteritis in Mediterranean countries: comment on the article by Salvarani et al. PMID- 1418013 TI - Interactions between antibodies and chondrocytes. PMID- 1418014 TI - Reduce serum uric acid levels before withdrawing antihyperuricemic therapy in patients with tophaceous gout. PMID- 1418015 TI - Clinical significance of hyaluronan in rheumatic diseases: comment on the articles by Goldberg et al and Woessner. PMID- 1418016 TI - Evidence for the presence of androgen receptors in the synovial tissue of rheumatoid arthritis patients and healthy controls. AB - OBJECTIVE: To study the presence of androgen receptors in the synovial tissue of male and female patients with rheumatoid arthritis (RA) and matched healthy controls. METHODS: Both site I (high affinity, low binding capacity) and site II (reduced affinity, higher binding capacity) androgen receptors were investigated in soluble and nuclear fractions of homogenized synovial samples, using the dextran-coated charcoal method. The finding of pure, high-affinity site I receptors in both fractions was considered indicative of androgen receptor positivity. In order to determine what type of synovial cell was positive for androgen receptors, cryosections of synovial tissues were immunostained with a specific monoclonal anti-androgen receptor antibody (MAb), using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with this MAb and specific MAb directed toward different macrophage/granulocyte antigens was also performed. RESULTS: Remarkable differences were found between male and female controls: Most males were positive for androgen receptors, and most females were negative. The fetomolar content of androgen receptor in the nuclear fraction was fairly constant, but the soluble fraction showed a higher femtomolar concentration in female RA patients than in controls of either sex, as well as in male RA patients compared with female RA patients. The androgen receptor-positive cells in both RA and control synovial cryosections were found by immunostaining to be macrophage-like synoviocytes, and were also found to be HLA-DR positive. CONCLUSIONS: The immunosuppressive action exerted by androgens might, at least in part, be mediated through their interaction with macrophage like synoviocytes functioning as antigen-processing and antigen-presenting cells in rheumatoid synovia. PMID- 1418017 TI - Antibodies in rheumatoid synovial fluids bind to a restricted series of protein antigens in rheumatoid synovial tissue. AB - OBJECTIVE: By searching the synovial fluid of patients with rheumatoid arthritis (RA) for antibodies that react to protein antigens in synovial tissue, we sought to identify putative antigens present in RA synovial tissue that might drive the pathologic immune response believed to be responsible for the joint inflammation. METHODS: Synovial tissue was homogenized in sodium dodecyl sulfate polyacrylamide gel buffer, electrophoresed, and analyzed by immunoblotting. RESULTS: Antibodies from synovial fluids of patients with RA bound to several proteins in rheumatoid synovial tissues, including a series of low (27.5-, 29-, and 30-kd), middle (43- and 53-kd), and high (140-, 164-, and 182-kd) molecular weight proteins. Most of these antigens were also detected in normal synovial tissue, and the high molecular weight proteins were also present in normal dermal, muscle, and liver tissues. The low and middle molecular weight proteins were detected in some, but not all, of the other normal tissues and in Jurkat cell lysates. Antibodies to the low and high series of proteins were present in all rheumatoid synovial fluids tested, but were generally absent from synovial fluids from patients with other arthritic diseases. CONCLUSION: These results show that antibodies in synovial fluids consistently react to several proteins in RA and normal synovial tissues. These antigens are possibly the same antigens provoking the T cell response in RA; therefore, understanding the mechanism of the immune response against these proteins will likely lead to important insight into the etiology of RA. PMID- 1418018 TI - Assessment of disease activity and impending flare in patients with systemic lupus erythematosus. Comparison of the use of complement split products and conventional measurements of complement. AB - OBJECTIVE: To determine whether increased levels of the complement split products generated in the activation of the alternative or classical pathway accompany more severe disease activity in patients with systemic lupus erythematosus (SLE) and whether these measurements are useful in predicting flares of disease. METHODS: Levels of Ba, Bb, SC5b-9, and C4d were measured in 380 plasma samples obtained from 86 SLE patients who were prospectively followed up for 15 months. RESULTS: In the 20 patients who had inactive disease at the initiation of the study, the mean values of all of the complement split products at entry were within the normal range. In the 47 patients with stable or moderate disease activity, levels of Ba were significantly increased, while the mean values for Bb, SC5b-9, and C4d did not differ significantly from those in patients with inactive disease. The mean entry value of each analyte was highest in the group of 19 patients who had the most severe disease activity at initial evaluation. Traditional measurements of complement, i.e., C3, C4, and CH50, followed similar trends, but did not discriminate between the 3 groups of patients as well as did measurements of the split products. Analysis of the disease course in the patients with inactive or stable/moderate disease revealed that an elevated level of C4d had the most sensitivity with regard to subsequent flare, while an elevated Bb level had the highest specificity and the greatest predictive value. CONCLUSION: These data suggest that elevated levels of complement split products, particularly products of alternative and terminal pathway activation, more accurately reflect disease activity than do conventional measurements of complement in SLE and may be useful in the prediction of impending disease flares. PMID- 1418019 TI - Neuropathologic findings in multi-infarct dementia associated with anticardiolipin antibody. Evidence for endothelial injury as the primary event. AB - OBJECTIVE: There are few reports describing histopathologic changes associated with the antiphospholipid antibody syndrome. We describe a patient with multi infarct dementia and antiphospholipid antibody syndrome, in whom a brain biopsy was performed. METHODS: Biopsy material from the left frontal cortex, including meninges, cortex, and underlying subcortical white matter, was investigated. Microscopic examination and special staining were performed. RESULTS: Microscopic examination showed lumenal occlusion by thrombi, and marked endothelial hyperplasia of small meningeal and cortical arterioles. CONCLUSION: These findings suggest that the pathogenesis of this cerebral vasculopathy is noninflammatory and is associated with reactive endothelial hyperplasia and thrombosis of small arterioles. PMID- 1418020 TI - Presence of small proteoglycan fragments in normal and arthritic human cartilage. AB - OBJECTIVE: To characterize the small proteoglycans decorin and biglycan in normal human patellar cartilage and in cartilage from individuals with chronic polyarthritis. METHODS: Cartilage extracts were chromatographed on DEAE-Trisacryl and further separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis before and after enzymatic degradation of the glycosaminoglycan chains. Decorin and biglycan were visualized after Western blotting, using core protein-specific polyclonal and monoclonal antibodies. RESULTS: Core protein fragments of both proteoglycans were observed even in normal cartilage. In the case of decorin they amounted to up to 15% of the immunoreactive material, and up to 5% of the core protein was glycosaminoglycan free. The quantity of decorin core protein was reduced in arthritic cartilage, but the core protein fragments represented up to 45% of the immunoreactive material. Different zones of cartilage differed in their content of the fragments. Evidence for an increased proportion of biglycan fragments was not obtained. CONCLUSION: Chronic polyarthritis leads to increased degradation of small proteoglycans. A considerable proportion of decorin fragments is retained in the tissue. These alterations may have a negative influence on the mechanical stability of tissue. PMID- 1418021 TI - Effect of intraarticular glycosaminoglycan polysulfate treatment on patellofemoral pain syndrome. A prospective, randomized double-blind trial comparing glycosaminoglycan polysulfate with placebo and quadriceps muscle exercises. AB - OBJECTIVE: To compare the effects of intraarticular (IA) injections of glycosaminoglycan polysulfate (GAGPS) plus basic conservative treatment with the effects of placebo injections plus conservative treatment and with the effects of conservative treatment alone in patients with chronic patellofemoral pain syndrome (PFPS). METHODS: We treated 53 patients who presented with chronic PFPS in 1 knee, according to 1 of the 3 protocols, in a prospective, randomized, double-blind study. Basic conservative treatment consisted of a 6-week program of quadriceps muscle exercise, elimination of symptom-producing activities, and oral doses of nonsteroidal antiinflammatory drugs. Physiologic saline served as placebo for injection. During the 6-week treatment period, 5 injections were given 1 week apart. Along with measurements of quadriceps strength, standardized subjective, functional, and clinical assessments were performed at presentation, after 6 weeks of treatment, and after 6 months. RESULTS: Results at 6 months indicated that IA injections of GAGPS or saline did not result in significant improvement beyond the good results achieved by the basic conservative treatment alone. More than two-thirds of the patients in each group experienced complete recovery. CONCLUSION: Neither the GAGPS injections nor the physiologic saline injections are more effective than conservative therapy in the treatment of chronic PFPS. Restoration of normal quadriceps muscle function to the affected knee seems to be crucial in treating PFPS. PMID- 1418022 TI - Appendicular and vertebral bone mass in ankylosing spondylitis. A comparison of plain radiographs with single- and dual-photon absorptiometry and with quantitative computed tomography. AB - OBJECTIVE: We assessed the prevalence, severity, and anatomic distribution of ankylosing spondylitis (AS)-related osteopenia (OP). METHODS: We studied 70 patients (60 males, 10 premenopausal females) with AS (according to the New York criteria) to determine the frequency of OP. Bone mass was measured by plain radiographs of the spine, by single-photon absorptiometry (SPA) of the distal and midshaft of the radius on the nondominant side, by dual-photon absorptiometry (DPA) of the lumbar spine (L2-L4), and by quantitative computed tomography (QCT) of the lumbar spine. RESULTS: SPA values for the radius mass were normal in males and in females, both at the distal and midshaft sites. In contrast, spine radiographs showed diminished density of the vertebral bodies in 69% of the males and 50% of the premenopausal females. Two male patients had had a vertebral compression fracture, and one female patient had had two. DPA values for the spine mass were significantly diminished in the male patients compared with the controls, but not in the female patients. Males with less severe AS also had the largest reduction in lumbar bone mineral content. In patients with more severe disease, lumbar bone mineral content was not statistically different from that in controls. QCT of the lumbar spine performed in 10 patients disclosed low density of the trabecular bone of the vertebral bodies, more so in those with more severe AS and syndesmophyte formation and/or apophyseal joint fusion, which contrasts with the normal values on DPA in these patients. CONCLUSION: Male patients with AS have axial osteopenia. In those who have very severe AS with new bone formation, DPA demonstrates normal values as a result of two opposite trends: central osteopenia (as assessed from QCT) and peripheral new-bone formation, which transforms vertebral bodies into long bones. This could modify the mechanical resistance of the spine and account for the propensity for anteroposterior transvertebral and transdiscal fractures after trauma in AS. PMID- 1418023 TI - Signal transduction in Sjogren's syndrome T cells. Abnormalities associated with a newly described human A-type retrovirus. AB - OBJECTIVE: To study the effects of a novel A-type retrovirus, detected in cocultures of lip biopsy specimens from Sjogren's syndrome (SS) patients and a human T cell line, on the infected T cells. METHODS: Interleukin-2 (IL-2) and IL 6 secretion were measured by bioassay and enzyme-linked immunosorbent assay, respectively, in the infected and noninfected cell lines. Surface antigen expression was determined by flow cytometry, using monoclonal antibodies. Protein kinase C (PKC) activity was measured using an enzyme assay kit, and calcium mobilization was assessed with a fluorescent probe. RESULTS: Infected cells expressed less CD4 and IL-6 receptor, but more HLA-DR, compared with noninfected cells. Infected cells also produced less IL-2 and displayed reduced PKC activation and calcium mobilization. A similar defect in calcium mobilization was detected in T cells from SS patients. CONCLUSION: These data suggest a possible involvement of the newly described retrovirus in T cell abnormalities. PMID- 1418024 TI - Quantitative immunohistologic criteria are superior to the lymphocytic focus score criterion for the diagnosis of Sjogren's syndrome. AB - OBJECTIVE: The aim of the present study was to evaluate the diagnostic value of quantitative immunohistologic criteria for Sjogren's syndrome (SS) in labial salivary gland biopsies. METHODS: Quantitative immunohistologic examination was performed on labial salivary gland biopsy samples from 80 healthy controls, 32 patients with primary SS, 14 patients with secondary SS, 5 with "probable" SS, 36 with keratoconjunctivitis sicca (KCS) with a lymphocytic focus score less than 1 on the lip biopsy, and 18 with rheumatoid arthritis (RA) without clinical evidence of SS. RESULTS: This is the first study to show that immunohistologic criteria for SS, based on the percentages of IgA-containing and IgG-containing plasma cells, are able to 1) confirm the diagnosis of SS in labial salivary glands of KCS patients in the absence of grade IV lymphocytic adenitis; and 2) distinguish between a grade IV focal lymphocytic adenitis in the labial salivary glands of SS patients and of RA patients without SS. CONCLUSION: Quantitative immunohistologic criteria were shown to be much more sensitive and disease specific than the widely accepted grade IV lymphocytic adenitis criterion, which corresponds to a lymphocytic focus score greater than 1, and these criteria should be included in the international diagnostic criteria for Sjogren's syndrome. PMID- 1418025 TI - Elevated serum levels of soluble interleukin-2 receptor in patients with Wegener's granulomatosis. Association with disease activity. AB - OBJECTIVE: To investigate whether soluble interleukin-2 receptor (sIL-2R), a marker of T cell activation, could be a useful marker of disease activity in Wegener's granulomatosis (WG). METHODS: Soluble IL-2R levels were determined by enzyme-linked immunosorbent assay. WG disease activity in 102 patients was assessed according to clinical features and levels of classic antineutrophil cytoplasmic antibody (c-ANCA) and C-reactive protein (CRP). RESULTS: Soluble IL 2R levels were higher in patients with generalized and active disease than in those with limited and inactive disease. In 25 patients with complete clinical remission, sIL-2R levels were significantly elevated, although levels of CRP and c-ANCA were normal. Eight of these 25 patients had disease relapses within 6 months. Levels of sIL-2R were significantly higher in patients who had relapses than in those who did not. Patients with clinically active WG but low c-ANCA or CRP levels had elevated levels of sIL-2R. CONCLUSION: Levels of sIL-2R correlate with disease activity in patients with WG, and may indicate imminent relapse. PMID- 1418026 TI - Tryptophan metabolism via the kynurenine pathway in patients with the eosinophilia-myalgia syndrome. AB - OBJECTIVE: To investigate the metabolism of L-tryptophan (LT) via the kynurenine pathway in patients with the eosinophilia-myalgia syndrome (EMS). METHODS: Measurement of LT, L-kynurenine, and quinolinic acid in plasma and cerebrospinal fluid (CSF) from subjects with EMS, from asymptomatic users of LT, and from normal subjects. RESULTS: Plasma LT concentrations were lower in untreated EMS patients (n = 5) than in corticosteroid-treated EMS patients (n = 5; P less than 0.05) and in asymptomatic users of LT (n = 5; P less than 0.05). Untreated EMS patients, who had discontinued LT weeks to months prior to study, had significantly higher plasma levels of L-kynurenine and quinolinic acid than did corticosteroid-treated EMS patients (P less than 0.05), normal subjects (P less than 0.02), and asymptomatic users of LT (P less than 0.05). EMS patients also had significantly elevated levels of L-kynurenine (P less than 0.05) and quinolinic acid (P less than 0.001) in CSF compared with normal subjects. After a 1-gm oral dose of LT, untreated EMS patients (n = 4) showed lower peak levels of LT and accentuated synthesis of L-kynurenine and quinolinic acid, compared with these values in corticosteroid-treated EMS patients (n = 2), who responded like normal subjects (n = 5). CONCLUSION: These data demonstrate that during the active phase of EMS, LT metabolism via the kynurenine pathway was accentuated, probably secondary to induction of the enzyme indoleamine-2,3-dioxygenase. Ingestion of large amounts of LT (median daily dose 1.5 gm) resulted in high concentrations of kynurenine-pathway metabolites in blood and extrahepatic tissues, which was accentuated in EMS patients and which may have played a significant role in the pathogenesis of the disease. PMID- 1418027 TI - Detection of autoantibodies to the SS-A/Ro antigen: comment on the article by Boire et al. PMID- 1418028 TI - On creativity. PMID- 1418029 TI - IX 207-887 in rheumatoid arthritis. A double-blind placebo-controlled study. AB - OBJECTIVE: To determine the efficacy and the safety of IX 207-887 treatment in rheumatoid arthritis. The IX compound [10-methoxy-4H-benzo(4,5)cyclohepta-(1,2 b)thiophene-4-yliden acetic acid] is effective in several animal models of rheumatoid arthritis and has a mechanism of action involving the inhibition of interleukin-1 release. METHODS: A double-blind, controlled trial of 16 weeks' duration comparing placebo with IX at a daily dosage of 800 mg or 1,200 mg (20 patients/group) was conducted. RESULTS: Thirteen patients withdrew from the study, 3 because of lack of efficacy (all in the placebo group) and 10 because of side effects (1 in the placebo group [skin rash] and 9 in the IX groups [skin rash in 5, intestinal disturbances in 2, hepatitis in 1, meningitis in 1]). Intent-to-treat analysis showed a statistically significant difference in the variations of clinical and laboratory parameters between the 3 groups. Between group comparisons showed an improvement in all these variables in the IX groups versus the placebo group. According to Paulus' criteria, 2 of the 20 placebo treated patients (10%), 9 of the 20 IX 800 mg-treated patients (45%), and 11 of the 20 IX 1,200 mg-treated patients (55%) were considered responders (P = 0.008). CONCLUSION: The findings of this study suggest that the tolerability of IX is acceptable in rheumatoid arthritis patients, and that IX is an effective slow acting drug for use in rheumatoid arthritis. PMID- 1418030 TI - Effect of nebracetam on nicotinic and muscarinic acetylcholine receptors expressed in Xenopus oocyte by injecting exogenous mRNA. AB - Using voltage- and current-clamp methods the effects of nebracetam 4-aminomethyl 1-benzylpyrrolidine-2-one hemifumarate, WEB 1881 FU, CAS 118607-07-1), a new agent with nootropic property, on the nicotinic (nAChRs) and muscarinic acetylcholine receptors (mAChRs) were studied, which were expressed in Xenopus oocytes by injecting E. electricus mRNA and rat brain mRNA, respectively. Simultaneous application of nebracetam (0.03-2 mmol/l) with acetylcholine (ACh) (0.01-1 mmol/l) inhibited the ACh-responses of both nAChRs and mAChRs, whereas preapplication of these concentrations of nebracetam for 30 s to 1 min potentiated such inhibition. A simple competitive inhibition model for the effects of both drugs simultaneously applied yielded the inhibition constant, K1 of 0.419 and 0.212 mmol/l for nAChRs and mAChRs, respectively, indicating that the action on mAChRs is a little more potent than on nAChRs. Nebracetam induced a concentration-dependent slight increase in inward currents on mAChRs but not on nAChRs. It is suggested that the direct effects of nebracetam on nAChRs and mAChRS, which were induced only by a rather high concentration, as compared with the clinically expected plasma level, may be a contributing factor to the clinical effectiveness of the drug only if there is some critical change in the sensitivity to the drug. PMID- 1418031 TI - Prophylactic effects of a new 1,5-benzothiazepine calcium antagonist on stroke in salt-loaded stroke-prone spontaneously hypertensive rats. AB - The influence of chronic treatment with clentiazem ((+)(2S,3S)-3-acetoxy-8-chloro 5-[2-(dimethylamino)ethyl]-2,3-dihydro- 2-(4-methoxyphenyl)-1,5-benzothiazepin-4 (5H)-one maleate, TA-3090), on blood pressure, incidence of stroke, stroke related mortality and histological changes of the brain and other organs were examined in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP that were fed an 8% NaCl-containing diet began to die of a stroke 3 weeks after salt-loading, accompanied by decreases in body weight and food intake. Most of the rats (16 out of 18) died by the 8th week of salt-loading. Chronic treatment with clentiazem (300 or 1000 ppm) delayed the occurrence of stroke and death in a dose-related manner without any hypotensive action when measured by the tail-cuff method. However, examination of circadian changes in arterial blood pressure with implanted cannula under a freely-moving condition 3 weeks after salt-loading revealed that 1000 ppm clentiazem produced significant hypotension in the dark phase but not in the light phase. Histological studies (3 weeks after salt-loading) showed that 1000 ppm Clentiazem significantly suppressed the cerebral and renal damages, and vascular hypertrophy in all organs studied. Thus, clentiazem prevents stroke and also protects renal damage and vascular hypertrophy in salt-loaded SHRSP. The hypotensive effect and organ protective action by clentiazem may be involved in its prophylactic action against stroke. PMID- 1418032 TI - Pharmacological profile of the new antidepressant levoprotiline. AB - The pharmacological properties of a new antidepressant, levoprotiline ((-)-R-a [(methylamino)methyl]-9,10-ethanoanthracene-9(10H)- ethanol hydrochloride, CGP 12103 A, CAS 76496-69-0) were investigated. 1. Central nervous system: Levoprotiline did not have any marked effects on the general behaviour of mice and rats at low doses, however it slightly suppressed the righting reflex and spontaneous motor activity of mice at higher doses. In rats, chewing behaviour and salivation were observed at higher doses. Levoprotiline had no effects on the traction test (mice) and inclined screen test (rats). Levoprotiline induced a slight drowsy EEG pattern, the effect being similar to that of typical antidepressants such as maprotiline or imipramine but the degree of potency of levoprotiline was less than that of the latter two drugs. Levoprotiline and maprotiline did not inhibit the arousal response induced by physostigmine, while imipramine clearly suppressed the response. 2. Respiratory and cardiovascular system: Heart rate decrease and QT prolongation were observed in anesthetized dogs. In an in vitro study, levoprotiline caused only slight stimulation of noradrenaline transmission in the isolated guinea pig atrium. 3. Smooth muscle: The effects of levoprotiline on the contractile response to histamine, acetylcholine and serotonin in the isolated guinea pig ileum were compared with those of maprotiline or imipramine. While levoprotiline potently inhibited the contractile response to histamine, its inhibition of acetylcholine-induced contraction was the weakest of the three compounds studied. No remarkable effect was observed in serotonin induced contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418033 TI - Variation of pharmacokinetics after oral administration of slow-release metoprolol tablets and pharmacogenetic considerations. AB - The maximum plasma concentrations (Cmax) after oral administration of 120 mg tablets of slow-release metoprolol (CAS 37350-58-6) to 75 Japanese healthy male volunteers and 15 arrhythmic patients were measured. Extensive and poor metabolizers after oral administrations of slow-release metoprolol tablets were classified by means of the frequency distribution of Cmax values. In addition, the frequency distribution of Cmax values after oral administration of slow release metoprolol 120 mg tablets was compared with that of conventional metoprolol 40 mg tablets. 1. Mean +/- S.E. values of Cmax, tmax and AUC0-24 after oral administration of slow-release metoprolol tablets to 75 healthy male volunteers and 15 arrhythmic patients were 95.3 +/- 6.6 ng/ml, 4.4 +/- 0.2 h and 1000.4 +/- 70.9 ng.h/ml, respectively. 2. The number of poor metoprolol metabolizers after the oral administration of slow-release tablets in 75 healthy volunteers and 15 patients was estimated to be 2 subjects (2.2%). 3. The frequency distribution of Cmax values after oral administration of conventional metoprolol tablets was similar to that of slow-release metoprolol tablets. In addition, from the result of this study and that obtained in another study, in which the frequency of poor metoprolol metabolizers in British people has been examined, it is concluded that the frequency of poor metoprolol metabolizers varies between ethnic groups (2.2% in Japanese population and 11.3% in British population. PMID- 1418034 TI - Synthesis, natriuretic, antikaliuretic and antimagnesiuretic properties of an acidic triamterene derivative. AB - 2,4,7-Triamino-6-(4-methanesulfonamidophenyl) pteridine (RPH 3048) is a new acidic triamterene derivative. Relevant physico-chemical constants were determined (solubility at pH 7.4 = 3.7 mg/l; logP at pH 7.4 = 0.2) and pharmacokinetic as well as pharmacodynamic properties were investigated, using male Wistar rats. After intravenous application of the test substances urine was collected, its volume and electrolyte composition determined, and the urine recovery of the drugs was analysed. The comparison of RPH 3048 with triamterene (CAS 396-01-0) revealed almost equipotent natriuretic and potassium-retaining effects for both drugs and an additional relative magnesium-sparing activity of RPH 3048. The urine recovery of RPH 3048 after 6 h was higher (20.6%) than that of triamterene (12.9%). No metabolite of RPH 3048 could be detected in the urine whereas a triamterene metabolite was found. Due to its good solubility in alkaline medium RPH 3048 could be dissolved (at pH 11-12) and then administered intravenously together with a loop diuretic (furosemide). Urinary electrolyte excretion following administration of two different combinations of RPH 3048 and furosemide (combination A: 12.5 mumol/kg RPH 3048 and 25 mumol/kg furosemide; combination B: 25 mumol/kg RPH 3048 and 25 mumol/kg furosemide) was compared to urinary electrolyte excretion of a control group and a group only treated with furosemide (25 mumol/kg). The additional application of RPH 3048 reduced in both groups potassium and magnesium excretion to control level but did not compromise furosemide induced natriuresis. In contrast to earlier investigations these results suggest that it is possible to develop acidic triamterene derivatives with potent antikaliuretic effects. PMID- 1418035 TI - Pharmacokinetics of azosemide in patients with T-drain after cholecystectomy. AB - In an open clinical trial the pharmacokinetics of orally administered azosemide (2-Chloro-5-(1H-tetrazol-5-yl)-4-[(2- thienylmethyl)amino] benzene sulfonamide. Luret, CAS 27589-33-9) was surveyed in a group of 10 patients with T-drain after cholecystectomy. The mean peak concentration was reached after 2.35 h (SE: 0.25 h) and was 474 ng/ml (142 ng/ml). The plasma elimination half-life was estimated to be 6.37 h (1.7 h). In 24 h 5.4% of the dose was excreted unchanged via urine and bile. Only a small fraction of the dose (0.53%) was recovered as glucuronide from urine and bile. Approximately 2% (0.74%) of the dose was excreted unchanged via bile. No other metabolites were detected. Plasma AUCO-24h was 3113 micrograms.h/l. The renal clearance of 27 ml/min (8.8 ml/min) was 3 times higher than the biliary clearance of 10 ml/min (2.4 ml/min). Azosemide is rapidly but incompletely absorbed and shows a longer half-life when compared with other loop diuretics. Enterohepatical circulation and first-pass effect seem to be less significant because low amount of azosemide is excreted via bile. PMID- 1418036 TI - Inhibitory effects of propiverine hydrochloride on the agonist-induced or spontaneous contractions of various isolated muscle preparations. AB - Inhibitory effects of propiverine hydrochloride (P-4, CAS 60569-19-9), a new drug which reduces the frequency of micturition, were studied on the agonist-induced or spontaneous contractions of various isolated muscle preparations. P-4 (10(-6) 10(-4) mol/l) inhibited both the KCl-induced contractions of isolated guinea-pig urinary bladder and ileum, and its IC50 values (mol/l) were 1.8 +/- 0.3 x 10(-5) (urinary bladder) and 1.3 +/- 0.4 x 10(-5) (ileum), respectively. The spontaneous contractions of isolated guinea-pig atrium, rat uterus and rabbit duodenum were unaffected by P-4 at 10(-6) mol/l, but they were inhibited by the drug at 10(-5) 10(-4) mol/l. Its IC50 values (mol/l) were 10(-4) greater than (guinea-pig atrium), 1.3 +/- 0.3 x 10(-4) (rat uterus), and 1.0 +/- 0.5 x 10(-4) (rabbit duodenum), respectively. P-4 (10(-5)-10(-4) mol/l) inhibited the KCl-induced contraction of isolated rabbit aorta and the histamine-induced contraction of isolated guinea-pig tracheal chain. P-4 (10(-4) mol/l) also inhibited the noradrenaline-(norepinephrine) induced contractions of isolated guinea-pig urethra and vas deferens. In these isolated muscle preparations, the values of IC50 (greater than 10(-4) mol/l) could not be calculated. These results indicate that the inhibitory activities of P-4 on urinary bladder and ileum are 10 to 100 times more potent than those on other organs. PMID- 1418037 TI - High pressure liquid chromatographic determination of the new non-steroidal anti inflammatory agent butibufen. AB - High performance liquid chromatography (HPLC) method for the determination and validation of a new non-steroidal anti-inflammatory agent, butibufen (CAS 55837 18-8), microencapsulated butibufen and its pharmaceutical forms--tablets, sachets (microencapsulated butibufen with excipients), microemulsion and cream--is described. Acetonitrile proved to be the best solvent for the extraction of butibufen from its pharmaceutical forms. The results submitted in this paper suggest that the HPLC method for the quantitative determination of butibufen is linear, accurate, precise and sensitive. PMID- 1418038 TI - Antitumor activity of some ruthenium derivatives in human colon cancer cell lines in vitro. AB - Six ruthenium derivatives were evaluated in vitro in two human colon cancer cell lines (SW707 and SW948) utilizing the microculture tetrazolium test (MTT) and cell counting with a Coulter Counter. The ruthenium compound sodium (tetrachloroimidazoledimethylsulfoxideruthenate)- bisdimethylsulfoxide (Na(RuDMSOimCl4)) showed the best efficacy in inhibiting cell proliferation of both colon cancer cell lines followed by the other DMSO ruthenium compound sodium (tetrachloroindazoledimethylsulfoxideruthenate) - bisdimethylsulfoxide (Na(RuDMSOIndCl4)), as demonstrated by IC50 values (80 and 90 micrograms/ml in SW707 and SW948 cell lines for Na(RuDMSOImCl4); 155 and 165 micrograms/ml in SW707 and SW948 cell lines for Na(RuDMSOIndCl4), respectively). Out of the ruthenium derivatives without DMSO, transindazolium - [tetrachlorobis(1H - indazole)ruthenate (III,N2)] (HInd[RuInd2Cl4(N2)]), was as active as its DMSO containing congener whereas trans-imidazolium- [tetrachlorobisimidazoleruthenate)(III)], (HIm(RuIm2Cl4)) was less active, as shown by the IC50 values: (HIm (RuIm2Cl4) = 250 and 260 micrograms/ml in cell lines SW707 and SW948; HInd[RuInd2Cl4(N2)] = 110 and greater than 200 micrograms/ml in cell lines SW707 and SW948, respectively). The other ruthenium derivatives containing pyrazole and triazole as ligands (trans - pyrazolium (tetrachlorobispyrazoleruthenate) (III), PzH(RuPz2Cl4) and triazolium(tetrachlorobistriazoleruthenate) (III), TrH(RuTr2Cl4)) were active only at high concentrations that cannot be regarded as realistic in vivo, as shown by the respective IC50 values: (PzH(RuPz2Cl4) = 1056 and 750 micrograms/ml in cell lines SW707 and SW948; TrH(RuTr2Cl4) = 350 and 300 micrograms/ml in cell lines SW707 and SW948). The promising activity of ruthenium compounds with DMSO, indazole and imidazole as ligands should be evaluated in vivo for elucidating their possible role in the treatment of colorectal cancer. PMID- 1418039 TI - Stereoselectivity in the disposition of chloroquine and desethylchloroquine in rabbits. AB - Stereoselective pharmacokinetic properties of chloroquine (CAS 54-05-7) and desethylchloroquine were investigated in rabbits by administration of the separate enantiomers according to a cross-over design. The terminal half-life was longer for (R)-chloroquine than for (S)-chloroquine. A striking difference was revealed in the concentrations of metabolites. The levels of (R) desethylchloroquine were higher than those of (S)-desethylchloroquine, resulting in a statistically significant higher AUC for the (R)-metabolite than for the (S) metabolite. PMID- 1418040 TI - Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. AB - The influence of alpha-lipoic acid (CAS 62-46-4) on the amount of intracellular glutathione (GSH) was investigated in vitro and in vivo. Using murine neuroblastoma as well as melanoma cell lines in vitro, a dose-dependent increase of GSH content was observed. Dependent on the source of tumor cells the increase was 30-70% compared to untreated controls. Normal lung tissue of mice also revealed about 50% increase in glutathione upon treatment with lipoic acid. This corresponds with protection from irradiation damage in these in vitro studies. Survival rate of irradiated murine neuroblastoma was increased at doses of 100 micrograms lipoic acid/d from 2% to about 10%. In agreement with the in vitro studies, in vivo experiments with whole body irradiation (5 and 8 Gy) in mice revealed that the number of surviving animals was doubled at a dose of 16 mg lipoic acid/kg. Improvement of cell viability and irradiation protection by the physiological compound lipoic acid runs parallel with an increase of intracellular GSH/GSSG ratio. PMID- 1418041 TI - Synthesis and antifungal activity of a series of difluorotritylimidazoles. PMID- 1418042 TI - In vitro and in vivo studies with flutrimazole, a new imidazole derivative with antifungal activity. AB - 1-[(2-Fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole (flutrimazole, UR 4056, CAS 119006-77-8) is a new topical imidazole antifungal agent which displays potent broad-spectrum in vitro activity against dermatophytes, filamentous fungi and yeasts, saprophytic and pathogenic to animals and humans (MIC = 0.025-5.0 micrograms/ml). In most of these studies the activity of flutrimazole was comparable to that of clotrimazole and markedly higher than that of bifonazole (MIC differences of greater than or equal to 1 order of magnitude). Tested against Scopulariopsis brevicaulis (8 strains), both flutrimazole and clotrimazole exhibited fungistatic and fungicidal activity, and clotrimazole appeared something less active (MIC = 0.3-2.5 micrograms/ml) than flutrimazole (MIC = 0.15-0.6 micrograms/ml). In animal experiments, topical application of 1% and 2% flutrimazole, as a cream or solution, was highly effective in models of rat vaginal candidiasis and guinea-pig trichophytosis, giving a rate of cured or cured plus markedly improved animals higher than 80%. Flutrimazole shares the mode of action of other imidazole or triazole-containing antifungals, i.e. inhibition of fungal lanosterol 14 alpha-demethylase, as it strongly inhibits ergosterol biosynthesis in a cell-free homogenate of Candida albicans, with an IC50 value of 0.071 mumol/l. PMID- 1418043 TI - Toxicity studies with flutrimazole. AB - Studies with 1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H- imidazole (flutrimazole, CAS 119006-77-8), a new topical imidazole antifungal agent, have been carried out to investigate the acute toxicity of the active substance in mice and rats, as well as the acute ocular and dermal irritation in rabbits, the dermal tolerance after repeated dose (21 days) applications in rabbits, and the sensitising, photoallergic and phototoxic potential in guinea pigs using 1% flutrimazole cream. LD50 values after oral or intraperitoneal administration were greater than or equal to 1000 mg/kg in both mice and rats, which reveal a very low acute toxicity of flutrimazole. No differences were found between the excipient and 1% flutrimazole cream in the acute ocular and dermal irritation studies in rabbits, the irritation indexes being indicative of no lesions due to flutrimazole. Cumulative dermal irritation studies in rabbits showed an improved local tolerance of a skin cream containing 1% flutrimazole as compared to a commercial skin cream containing 1% clotrimazole. The irritation indexes were 1.2 and 3.7, respectively (p less than 0.01). The corresponding histophatological findings confirmed the better local tolerance of 1% flutrimazole cream. Furthermore, it has been found that flutrimazole cream lacks sensitising potential (Magnusson and Kligman test), is also devoid of phototoxic potential and does not induce photoallergic reactions in guinea pigs, these data being confirmed by histopathological studies. These results, together with the very slight systemic absorption rate of flutrimazole from the 1% topical drug form, clearly show that no restrictions should be taken in the use of the cream for reasons of systemic toxicity or dermal tolerance. PMID- 1418044 TI - Percutaneous absorption and skin distribution of [14C]flutrimazole in mini-pigs. AB - The percutaneous absorption and skin distribution of a skin cream containing 1% 14C-labelled 1-[(fluorophenyl) (4-fluorophenyl) phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) was studied in minipigs. The same dose of flutrimazole was administered i.v. and topically (as a cream) on scarified skin according to a crossover protocol. Samples of urine and faeces were taken at various intervals after administration, and radioactivity was measured. The percentage of radioactivity accumulated in urine after topical and intravenous administration were 1.46% and 41.7%, respectively. In faeces, the percentage of radioactivity observed was 6.0% after intravenous administration, and none was detected after topical application. In order to study the distribution and penetration of [14C]flutrimazole, the cream was applied to intact and scarified skin. At various intervals after administration, skin samples were taken. The samples for the autoradiographic studies were cut transversely, and for the measurement of the levels of radioactivity at different skin depths, slices were cut parallel to the cutaneous layers. The results obtained indicate that [14C]flutrimazole penetrates quickly into the different epidermic layers and is retained mainly in the strata spinosum, granulosum and basale. The stratum basale possibly acts as a selective barrier preventing the penetration of the compound into the dermis. The percentage of radioactivity in the stratum corneum is lower than that detected in all the other epidermic layers taken together. The stratum corneum offers low resistance to penetration by the flutrimazole, which very probably crosses the epidermic strata by a transcellular route. PMID- 1418045 TI - Pharmacokinetic study of [14C]flutrimazole after oral and intravenous administration in dogs. Comparison with clotrimazole. AB - This trial involved a comparative study using 6 Beagle dogs on the pharmacokinetics of 14C-labelled 1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl] 1H-imidazole (flutrimazole, CAS 119006-77-8) and [14C]clotrimazole labelled in the imidazole ring. On the basis of a cross-over trial, each animal received a dose of 5 mg/kg (approx. 100 microCi) [14C]flutrimazole and [14C]clotrimazole, both intravenously and orally. The levels in plasma, urine and faeces of the total radioactivity, unchanged drug and the [14C]imidazole formed by metabolization of the unchanged drug were determined. Flutrimazole presented a biological half-life (t1/2) of 14.4 +/- 3.8 h and a clearance (Cl) of 6.7 +/- 0.8 l/h, while the values for clotrimazole were very different: t1/2 4.6 +/- 0.8 h and Cl: 13.6 +/- 1.0 l/h. After oral administration a fraction of absorbed dose (f) of 78 +/- 21% and bioavailability of 8.9 +/- 6.1% were calculated for flutrimazole. For clotrimazole, these were: 52 +/- 10% and 4.9 +/- 1.9%, respectively. Both drugs showed a significant first-pass effect, with 90% of the absorbed dose being metabolized before reaching the systemic circulation. The total recovery of radioactivity in faeces and urine 5 days after i.v. and oral administration was 58% and 68%, respectively, for [14C]flutrimazole, and 81% and 79% for [14C]clotrimazole. In both cases, most of the radioactivity was recovered in the faeces. The high radioactivity obtained in faeces after i.v. administration of both drugs confirms biliary elimination. For both flutrimazole and clotrimazole, less than 1% of the total recovered in the urine after i.v. administration was recovered as unchanged drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418046 TI - Local and systemic tolerance of flutrimazole skin creams following single and repeated topical application in healthy volunteers. AB - A double-blind, randomized phase I study was performed in 21 healthy volunteers to evaluate the dermal tolerance of skin creams containing 1% and 2% 1-[(2 fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) or only the excipient, versus a commercial skin cream containing 1% clotrimazole. The study was carried out using the patch-test procedure performed in three stages: 1. single application in the back skin; 2. induction period (usage test) using three skin areas on the volar side of the forearm of each subject, where skin cream samples were applied once a day for a period of three weeks; and 3. after a wash-out period of two weeks, challenge applications in the back and forearm skin. The systemic tolerance of the formulations was also tested. There was no evidence of allergic sensitization after the application of flutrimazole creams, or their excipients, with signs of mild and doubtful skin reactions being observed in few subjects with all formulations. Furthermore, no systemic side effects after topical administration were detected throughout the study. PMID- 1418047 TI - Pharmacokinetic profile of [14C]flutrimazole following single topical application in normal and scarified skin of healthy volunteers. AB - 14C-labelled 1-[(2-fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H- imidazole (flutrimazole, UR-4056, CAS 119006-77-8) was administered topically (dermally) in three male volunteers to normal skin and scarified skin, respectively. Blood, urine and faeces were collected and radioassayed by liquid scintillation counting techniques. After topical application to healthy skin area, less than 1% of flutrimazole was absorbed percutaneously from a 1% cream and the amount absorbed was excreted with the urine. Following administration of the drug to scarified skin, the proportions absorbed were very similar to those measured after application to normal skin. About 0.5% of the administered dose is recovered in urine. The absorbed amount of drug leads to very low concentrations in the circulation, lower than a few ng/ml. PMID- 1418048 TI - Rated performance, cardiovascular and quantitative EEG parameters during simulated instrument flight under the effect of terfenadine. AB - In a double-blind placebo-controlled randomized two-phase cross-over study comprising 10 (5/5) male subjects the effect of oral therapeutic doses of terfenadine (Teldane, CAS 50679-08-8) on rated performance, systolic and diastolic blood pressure, heart rate and the electroencephalogram of the subjects in an instrument flight (IF) procedure trainer was investigated. Terfenadine did not influence systolic and diastolic blood pressure, heart rate and the specific performance of subjects during instrument flight procedures. Under terfenadine the quantitative EEG (qEEG) showed more %alpha, especially %alpha 2 during rest and to a lesser extent during instrument flight procedures of the subjects. As a result the vigilance dynamics was increased. In the %beta band especially %beta 2 was increased only during instrument flight activities. The ratio theta/alpha was reduced during rest and during activities. Thus all these quantitative EEG indicators do not show a decrease in the level of vigilance nor are they indicative of signs of drowsiness during rest and during instrument flight activities under terfenadine. The results are discussed. PMID- 1418049 TI - Quantification of dechelation of gadopentetate dimeglumine in rats. AB - An animal model was developed in order to estimate a potential in vivo dechelation of gadopentetate dimeglumine (Gd-DTPA; CAS 86050-77-3) and to provide information concerning the chemical form of long-term gadolinium not excreted. Excretion kinetics and biodistribution of 153Gd-DTPA and Gd-[14C]DTPA were studied in 2 groups of rats following the intravenous injection of 0.5 mmol/kg Gd DTPA. Differences in the elimination and biodistribution profiles between the quantities of 153Gd and 14C radioactivity were taken as evidence for dechelation of Gd-DTPA within the body leading to a release of Gd ions. Statistically significant differences were observed in excretion and whole-body retention indicating an in vivo dechelation of less than 1% of the injected dose. 30% of the released Gd ions were excreted via urine and feces during the 21-day time interval. 21 days p.i., 70% of the released Gd ions remained in the body producing a significant 153Gd excess in liver, spleen, and the bones representing the principal target organs of released Gd ions after intravenous injection of Gd DTPA. More than 96% of the released Gd ions found in the body 21 days p.i. were deposited in the bones. Liver and spleen showed minor contributions. In any case, the chemical form of the gadolinium present in liver, spleen, and the bones could predominantly be assigned to translocated Gd ions resulting from dechelation of Gd-DTPA. PMID- 1418050 TI - Human recombinant interleukin-1 alpha and beta and articular tissue integrity. An in vivo study on hens and rats. AB - Human recombinant interleukin-1 alpha or beta was injected intraarticularly several times into the knee joints of rats and hens at different dosages (50-2000 ng) and intervals. No loss of cartilage detectable by width of the radiological joint space and no degenerative changes of subchondral bone could be observed during 16 weeks using X-ray analysis. The macroscopical examination of articular cartilage of hens after this period and of rats after one year showed no morphological cartilage damages. These data suggest that human recombinant Il-1 alpha and beta alone may not be sufficient to induce a progressing osteoarthritic process in these animals. PMID- 1418051 TI - Behavioral characterization of the new potent nonselective dopamine agonist pergolide. AB - Pergolide (LY127809, CAS 66104-23-2), a non-selective dopamine agonist, was evaluated for broad behavioral properties in a wide range of pharmacological tests. The selective dopamine2(D2) agonist, bromocriptine, served as a reference standard for those tests where behavioral activity was noted with pergolide. Pergolide and bromocriptine were administered orally to mice at doses of 0.3-30 and 3-300 mg/kg, respectively. Both compounds produced biphasic effects on spontaneous activity, increased hexobarbital-induced sleep time, and lowered mouse body temperature. Qualitative changes with pergolide were observed with some mice showing hyporeactiveness, ptosis, slowed respiration and placing loss. Reserpine-induced hypothermia was reversed by pergolide with significant increases in the body temperature of reserpine-treated mice. However, a further reduction in the body temperature of reserpinized hypothermic mice was seen following bromocriptine administration. Acetic acid-induced writhing and performance on the rotarod were both impaired by higher doses of pergolide. Bromocriptine administration also reduced writhing at higher doses but did not alter performance on the rotarod. Pergolide had no effect on seizure activity as evaluated by electroshock, pentylenetetrazol (pentetrazol) or strychnine. Oxotremorine-induced tremors and salivation, grip strength, and tail-flick were not affected by pergolide. Neither pergolide nor bromocriptine altered established shuttle-avoidance behavior in rats at oral doses of 0.1 to 30 mg/kg. Behavioral assessment of pergolide in dogs was complicated by severe emetic responses at clinically relevant doses greater than 0.003 mg/kg. In summary, these data suggest that pergolide produces a behavioral profile which is characteristic of dopaminergics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418052 TI - General pharmacology of pergolide in animals. 2nd communication: gastrointestinal, renal and miscellaneous studies. AB - Pergolide mesylate ((8 beta)-8-[(methylthio)methyl]-6-propylergoline monomethanesulfonate, LY 127809, CAS 66104-23-2) is a novel and potent dopamine agonist marketed for treating the symptoms of Parkinson's disease. The potential secondary pharmacological effects of this agent on the gastrointestinal and renal systems, as well as effects on local anesthesia, hemolysis, platelet aggregation, circulating blood glucose, primary antibody production, and the acute inflammatory response were examined. Pergolide exhibited significant pharmacological effects in gastrointestinal, renal and anti-inflammatory tests at high oral doses. Pergolide was essentially inactive in blood hemolysis, platelet aggregation, primary antibody production and local anesthesia testing. In summary, these studies confirm the pharmacological selectivity of pergolide, and indicate a low potential for secondary pharmacological side effects upon the functions tested at clinically relevant doses. PMID- 1418053 TI - Effects of mergocriptine on cerebral circulation and metabolism in cats. AB - Mergocriptine (CBM 36-733, CAS 81968-16-3) is an ergot alkaloid derivative and a dopaminergic agonist. Effects of mergocriptine on cerebral circulation and metabolism were examined by monitoring cerebral tissue oxygen and carbon dioxide tension (BrPO2, BrPCO2), cerebral blood flow (CBF) and blood pressure (BP) in 10 cats. Mergocriptine (10 micrograms/kg) infused into the carotid artery produced a significant increase in CBF during the administration followed by a decrease in BrPO2 in parallel with a significant decrease in BP. PMID- 1418054 TI - Memantine in the treatment of mild to moderate dementia syndrome. A double-blind placebo-controlled study. AB - The efficacy and the tolerability of memantine (1-amino-3,5-dimethyladamantane hydrochloride, Akatinol Memantine, CAS 41100-52-1) were investigated in patients with mild to moderate dementia syndrome in a randomized two-centre placebo controlled clinical study. The test substance was administered at a dose of 10 mg/d from day 1 to day 3 and then at a dose of 2 x 10 mg/d from day 4 to the end of treatment after 42 days. Altogether, 88 patients were recruited to the study; their average age was 71.5 years. The efficacy of memantine was judged on the basis of the baseline/6 week differences in the total sum scores of the Clinical Assessment Geriatric Scale (SCAG), the Gottfries-Brane-Steen Scale (GBS), the SCAG and GBS subscales and the global assessment of the change in the patient's condition. The effects of memantine on performance were studied with the aid of psychomotor tests and a behaviour investigation relating to activities of daily living (ADL). The tolerability of memantine was assessed on the basis of the doctor's global assessment and of entries on structured documentation forms (DOTES/TWIS). Further safety parameters--in the form of clinicochemical tests and measurements of blood pressure and heart rate--were also monitored during the study. On both the psychopathological measurement level (SCAG, global assessment of the change in the patient's condition) and the behavioural level (GBS), confirmatory statistical analysis brought to light significant differences between memantine and placebo (p less than or equal to 0.05), these differences showing a superiority of memantine. The tolerability of memantine was good in the main. The observed adverse reactions were not serious and, except in 3 patients, were rated as causing little or no impairment. The present clinical study demonstrates the efficacy of memantine in patients suffering from mostly moderate dementia syndrome. Clinical and statistically relevant improvements in the dementia-induced disturbances were found on the both the psychopathological level (SCAG, CGI) and the behavioural level (GBS). On the performance level also, the ADL behaviour investigation detected a highly significant improvement in the quality of performance of instrumented activities of daily living under memantine. Also the time taken to carry out these tasks was significantly reduced in comparison with placebo. PMID- 1418055 TI - Bioavailability of vinpocetine and interference of the time of application with food intake. AB - In a pilot study based on an open cross-over design involving four phases, the relative bioavailability of the eburnamenine derivative vinpocetine (CAS 42971-09 5) was investigated in 8 healthy volunteers in relation to different times of drug administration relative to food intake. The substance was applied orally as 10 mg film tablets. The areas under the plasma concentration-time curves (AUC) amounted to 27.3 +/- 18.1 ng.h/ml (fasting) and 42.8 +/- 27.4 up to 54.3 +/- 38.4 ng.h/ml (non-fasting, intake before and after meal, resp.). The relative bioavailability under non-fasting conditions was found to be approx. 60 to 100% higher than under fasting conditions. PMID- 1418056 TI - Growth-promoting effect of a protein-free hemodialysate used in situations of hypoxia and for tissue repair as measured via stimulation of S6-kinase. AB - Solcoseryl is the low-molecular weight fraction of calf blood as manufactured by counterflow dialysis. This hemodialysate (HD) is in clinical use in situations involving hypoxia and for the normalization of tissue repair. The influence of the HD on ZR-75 cells was tested. These cells preferably express receptors for Epidermal Growth Factor (EGF)/Transforming Growth Factor alpha (TGF-alpha) or Somatomedin C (SMC = insulin like growth factor I resp. ILA-I) and react upon stimulation by enhancement of their S6-kinase activity, the latter being a prerequisite for growth. The functional presence of one or several of these peptide growth factors should therefore reflect in a stimulation of S6-kinase activity. PMID- 1418057 TI - Synthesis and cardiovascular properties of furazanyl-1,4-dihydropyridines and of furoxanyl analogues. AB - A series of furazanyl- and furoxanyl-1,4-dihydropyridines has been synthesized and tested for their cardiovascular activity. The new compounds showed a modest activity in comparison with nifedipine and some selectivity for the myocardial muscle. The most active compound was diethyl 1,4-dihydro-2,6-dimethyl-4-(3-phenyl 4-furoxanyl)-3,5-pyridine dicarboxylate, 4d. PMID- 1418058 TI - Bioavailability and metabolism of isosorbide dinitrate from a transdermal spray. AB - The plasma pharmacokinetics of isosorbide dinitrate (ISDN), isosorbide-2-nitrate (IS-2-N) and isosorbide-5-nitrate (IS-5-N) were investigated in 12 healthy volunteers after a single cutaneous administration of 60 mg ISDN (CAS 87-33-2) in the form of a solution sprayed onto the skin (TD Spray Iso Mack), in comparison with an intravenous infusion of 5 mg ISDN. After the intravenous dose, the apparent steady state volume of ISDN distribution came to 179.9 l, total body clearance was 3.14 l min-1, and terminal half-life was 79 min, on average. The transdermal absorption resulted in an average peak plasma concentration of 6.9 ng ISDN ml-1 at 5 h after the administration. ISDN concentrations between 1 and 5 ng ml-1 were maintained over at least 15 h. On average, 16.5% of the topically applied ISDN reached the systemic circulation. Total variations in Cmax (CV = 47.9%) and AUC (CV = 36.0%) of transdermal ISDN were similar to those usually observed after oral ISDN. PMID- 1418060 TI - Pharmacokinetic study of tolmetin in the rat. AB - The pharmacokinetics of tolmetin (CAS 26171-23-3) was studied in male Wistar rats after intravenous and oral administration of 32.95 mg/kg. After intravenous administration of the drug, it was shown that the most probable model was the two compartment-open model with Michaelis-Menten elimination. After oral administration, the drug was absorbed rapidly (K01 = 0.1304 min-1). The bioavailability was 96.94% and the drug was mostly excreted as 1-methyl-5-(4 carboxybenzoyl)-1H-pyrrole-2-acetic acid, while the excretion of the unchanged drug was 6.12%. PMID- 1418059 TI - Pharmacological studies of the new antiinflammatory agent 3-formylamino-7 methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne. 1st communication: antiinflammatory, analgesic and other related properties. AB - The antiinflammatory, analgesic and antipyretic activities of 3-formylamino-7 methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-on e (T-614, CAS 123663-49-0) were investigated in various animal models and compared with those of nimesulide, indomethacin and ibuprofen. The antiinflammatory potency of T-614 on carrageenin induced paw edema, paper disk granuloma and established adjuvant arthritis was greater than that of ibuprofen, but slightly lower than those of nimesulide and indomethacin. In acute inflammatory models, unlike indomethacin, T-614 suppressed the edemas provoked by dextran and bromelain in rats, but its inhibitory action on ultraviolet erythema in guinea-pigs was weak. Although the analgesic activity of T-614 was hardly demonstrated in writhing tests in mice, its potency against the inflammatory pain such as Randall-Selitto test, adjuvant-induced hyperalgesia and antigen-induced arthritic pain in rats was superior to that of ibuprofen. Moreover, it had a potent analgesic effect on urate-induced synovitis in dogs. T 614 exerted a prompt and strong antipyretic effect in both yeast-induced febrile rats and lipopolysaccharide-induced febrile rabbits. T-614 had virtually no gastrointestinal ulcerogenic action and did not affect water and sodium excretion in rats. T-614 is a novel antiinflammatory compound with different pharmacological properties from that of the reference drugs. PMID- 1418061 TI - Anti-inflammatory, analgesic, and antipyretic effects and gastrointestinal toxicity of the new anti-inflammatory drug N-(3-[3 (piperidinylmethyl)phenoxy]propyl)-carbamoylmethylthio ]ethyl 1-(p-chlorobenzoyl) 5-methoxy-2-methyl-3-indolylacetate. AB - The anti-inflammatory, analgesic, and antipyretic effects and gastrointestinal toxicity of N-(3-[3-(piperidinylmethyl) phenoxy] propyl)- carbamoylmethylthio] ethyl 1-(p-chlorobenzoyl) 5-methoxy-2-methyl-3-indolylacetate (CP-331, CAS 127966 70-5), a new anti-inflammatory drug, were evaluated using indomethacin as a control. CP-331 exerted anti-inflammatory, analgesic and antipyretic effects on the models of carrageenin-induced paw edema, increased vascular permeability, ultraviolet light-induced erythema, granuloma proliferation, adjuvant arthritis, inflammatory pain, and yeast-induced fever. However, these effects were observed at a molar level similar to or higher than that of indomethacin. In addition, CP 331 influenced more markedly than indomethacin the delayed type hypersensitivity to sheep red blood cells. On the other hand, CP-331 did not damage the gastric mucosa even at a high dose of 1,000 mg/kg and also induced slighter damage to the intestinal mucosa than indomethacin. Thus, CP-331 exerted anti-inflammatory, analgesic, and antipyretic effects but without showing gastric toxicity, which is a common side effect of anti-inflammatory drugs. These results suggest the clinical applicability of this drug in the long-term therapy of inflammatory diseases such as rheumatoid arthritis. PMID- 1418063 TI - Induction of glutathione S-transferase activity by curcumin in mice. AB - Curcumin, a natural constituent of Curcuma longa (turmeric, CAS 458-37-7), has been studied for its induction of glutathione S-transferase activity in mice. At a dose of 250 mg/kg orally for 15 days, the enzyme activity in liver was increased by 1.8 fold. Its effect on other tissues like stomach, small intestine, lungs, kidney was not significant. Curcumin also depleted sulfhydryl levels in tissues, especially in stomach where 45% depletion was observed. PMID- 1418062 TI - Effects of salbutamol and bitolterol mesilate on pO2 levels in asthmatic patients and healthy volunteers. AB - The hypoxic effects of salbutamol 200 micrograms (CAS 18559-94-9) and bitolterol mesilate 740 micrograms (Biterol, CAS 30392-41-7), both administered by pressurized aerosol, were assessed by transcutaneous pO2 monitoring in 18 asthmatic subjects and in 12 normal volunteers. Unlike the latter, the asthmatics showed a highly significant difference in ptcO2 time course after the two drugs. After bitolterol mesylate the decrease in ptcO2 was much more gradual and the maximal decrease showed a 10-min time lag vs. salbutamol, which may partly explain the well known chronotropic effect of bitolterol. The clinical importance of the beta 2-induced hypoxemia may be related more to the dynamics of the ptcO2 decrease than to its absolute magnitude, which is usually fairly moderate. PMID- 1418065 TI - Missing neutral DNase activity in lymphocytes and phytohemagglutinin-stimulated lymphocytes after high dose methotrexate therapy. AB - After high dose methotrexate (CAS 59-05-2) therapy of children with non metastatic osteosarcoma the neutral DNase activity is missing in lymphocytes and in phytohemagglutinin (PHA)-stimulated lymphocytes. The neutral DNase activity reappeared in lymphocytes 14 days and in PHA-stimulated lymphocytes 10 days after the end of therapy. The DNA polymerase activity is low when neutral DNase is missing and increases when neutral DNase activity reappeared. The neutral DNase activity in lymphocytes and in PHA-stimulated lymphocytes is probably identical with DNase I. Drug induced changes in DNA conformation can enhance DNase I cleavage rate. It is assumed, that high dose methotrexate alters DNA conformation and therefore binds DNase I; after this, free DNase I is no more detectable. PMID- 1418064 TI - Crystalline lactulose in the therapy of hepatic cirrhosis. Evaluation of clinical and immunological parameters. Preliminary results. AB - Crystalline lactulose (Laevolac Cristalli, CAS 4618-18-2), a pure form of the disaccharide widely employed in the therapy of complications of liver cirrhosis, was administered, after a pharmacological wash-out of 10 days and following a randomized design, to 10 cirrhotic patients for 30 days at the dosage of 60 g/d, while another 10 subjects with similar characteristics received no treatment. Besides the parameters usually monitored for the evaluation of liver function and state of hepatic encephalopathy, immunological patterns such as lymphocyte subpopulations CD3, CD4, CD8, CD16(NK), CD25 and antibacterial activity against Ty2 strain of Salmonella typhi were evaluated. At the end of the study (day 30) a significant decrease of blood ammonia was observed, as expected, only in the group treated with lactulose with respect to the control group, as well as a significant increase of CD16 and antibacterial activity (1/3); an enhanced level of CD25, although not significant, was also noticed in the treated group with respect to the control group. These findings seem to show an effect of activation on cell-mediated immune system depressed during liver cirrhosis, produced by lactulose. Further studies are needed to confirm these data and to clarify the possible mechanisms involved. PMID- 1418066 TI - Efficacy and safety of cefotiam hexetil in the treatment of ear, nose and throat infections. AB - In 60 patients suffering from acute ear, nose and throat infections the efficacy and safety of cefotiam hexetil (SCE-2174, CAS 61622-34-2) which is a pro-drug of cefotiam was studied. The clinical success rate (improvement/cure) achieved with a daily administration of 600 mg was 90%. In 63% of the cases being evaluable for bacteriological response an eradication of the causative pathogens at the end of the treatment period was found. The majority of the patients tolerated well the compound. Side effects which were possibly, likely or definitely related to the treatment were observed in 12 patients. In 7 of these patients the treatment had to be stopped due to side effects which is equivalent to an intolerance rate of 12%. The data obtained in the present study indicate that cefotiam hexetil is a potent drug for the treatment of acute and acute on top of chronic infections of the upper aerodigestive tract. PMID- 1418067 TI - Enhancement of the penetration of dithranol and increase of effect of dithranol on the skin by liposomes. AB - An assessment was made in healthy skin of dithranol erythema caused by a 10-min occlusive application of 0.5% dithranol (CAS 1143-38-0) in liposomal gel (Natipide II) with and without the addition of 3% salicylic acid, and of 0.5% dithranol in vaseline and in a removable standard ointment base, both with 3% salicylic acid. Both liposomal preparations led to a significant potentiation of the dithranol erythema. The results indicate a strong promotion of the penetration of dithranol by the liposomal gel. PMID- 1418068 TI - Platelet-activating factor antagonists in experimental shock. AB - Platelet-activating factor (PAF) at 10 micrograms/kg i.v. induced profound hyperkalemia, changes of hematological parameters, patterns of ECG, and acid-base balance in rats. In separate experiments infusions of PAF at 30 ng/kg/min or injection of endotoxin from E. coli (15 mg/kg i.v.) induced a marked drop in blood pressure. All these changes were antagonized by pretreatment or post treatment (in case of hypotension) by the selective hetrazepinoic PAF antagonists apafant (WEB 2086, CAS 105219-56-5; 0.1-5 mg/kg i.v.), bepafant (WEB 2170, CAS 114776-28-2; 0.05-1.0 mg/kg i.v.), or STY 2108 (0.01-0.1 mg/kg), respectively. The results support the view that PAF can mimic features of endotoxin shock and that the hetrazepines (like apafant, bepafant) are useful tools to clarify the role of PAF in such conditions. PMID- 1418069 TI - Synthesis of laminarin sulfates with anticoagulant activity. AB - Laminarin sulfates were synthesized without significant degradation of the genuine laminarin chain using SO3/pyridine complex as a sulfation reagent. 6 derivatives with a degree of sulfation (d.s.) ranging from 0.30 to 2.26 could be obtained. According to methylation analysis the C-6-OH-groups of the glucose molecules were preferentially substituted, followed by the OH-groups at C-2 and C 4. The derivatives Lam S1 (d.s. = 0.30) and Lam S2 (d.s. = 0.64) showed no activity in the blood coagulation tests. With increasing d.s. the anticoagulant activity increased until an optimum d.s. of 1.49. Anticoagulant laminarin sulfates showed significant activity in the activated partial thromboplastin time (APTT) test but were less active in the anti-Factor Xa as well as anti-Factor IIa assay. Therefore, the anticoagulant activity of the synthesized laminarin sulfates is due to the interaction at an early stage of the coagulation cascade and neither to a direct inhibition of Factor Xa and IIa nor to an indirect effect mediated by antithrombin III. PMID- 1418070 TI - [The effect of co-dergocrine mesylate on erythrocyte deformability of hyperosmolar blood in vitro]. AB - Addition of low doses of co-dergocrine mesilate (CAS 8067-24-1), a drug containing a mixture of hydrated ergot alkaloids to hyperosmolar blood in vitro leads to a dose-dependent increase in erythrocyte filterability through a 8 mu filter system. The concentrations of co-dergocrine mesilate used in the present experiments ranged from 0.04675-6.0 mg/100 ml blood. Blood samples were incubated for 90 min at 37 degrees C, measuring temperature was 37 degrees C. It could be shown that the drug-induced increase in erythrocyte filterability was not dependent on the presence of leucocytes. At higher osmolarity values, when the erythrocytes were more rigid, higher concentrations of codergocrine mesilate were needed in order to obtain a comparable improvement in red cell deformability. PMID- 1418071 TI - Effect of drug therapy on the relapse of peptic ulcers. 1st communication: the effect of acute therapy. AB - The following study was conducted in order to investigate the effect of drug therapy on the relapse of peptic ulcers. Acute therapy with pirenzepine (Gastrozepin, CAS 28797-61-7) (100 mg/d) or cimetidine (CAS 51481-61-9) (800 mg/d) was given to 402 patients with peptic ulcers using the envelope method. Subsequently, 1-year maintenance therapy with pirenzepine (75 mg/d) or placebo was carried out in a double-blind study in 251 patients who had been cured within 3 months. During the study period, an endoscopic examination was repeated regularly to study the relapse of ulcers. When the results were stratified and analyzed by Cutler-Ederer's life table method to see changes in relapse over time, it was noted that the acute therapy for active ulcers did have an influence on the course of relapse after the ulcer lesions had been cured. Pirenzepine, a M1 antagonist, was superior to cimetidine, a H2 antagonist, in the prevention of relapse of ulcers after they had been cured. The results suggest that the prevention of relapse of peptic ulcers should be started at the stage of acute therapy for active ulcers and that care should be taken in selecting drugs. The results also suggest that the natural history of peptic ulcers with respect to their relapse can be modified to a certain extent by drug therapy although the period for such cannot be specified. PMID- 1418072 TI - Effect of drug therapy on the relapse of peptic ulcers. 2nd communication: the effect of maintenance therapy. AB - One-year maintenance therapy with pirenzepine (Gastrozepin, CAS 28797-61-7) (75 mg/d) or placebo was performed in a double-blind fashion in 251 patients to investigate the relapse by means of endoscopic examinations repeated every 3 months. Enrolled were the patients who had been cured within 3 months by acute therapy with either pirenzepine or cimetidine randomly given by the envelope method. When the results were analyzed by Cutler-Ederer's life table method to monitor manifestation of relapse, the maintenance therapy with pirenzepine did not show any significant difference from placebo in all the patients enrolled. However, stratified analysis according to various combinations of background factors revealed that there was significant difference in 1-year cumulative non relapse rates between the pirenzepine maintenance therapy group and the placebo group, suggesting prophylactic effect of the maintenance therapy with pirenzepine on relapse. An increase of daily dose more than 75 mg in maintenance therapy may be expected to display the prophylactic effect of pirenzepine on ulcer relapse in a definite manner. PMID- 1418073 TI - [Bioequivalence and bioavailability after single administration of effervescent ranitidine tablets]. AB - An open two-way cross-over study in 12 healthy male volunteers was performed in order to determine the relative bioavailability of a 150 mg ranitidine (Zantic, CAS 66357-35-5) effervescent tablet sweetened with saccharine in comparison to the 150 mg standard ranitidine dispersible tablet (Trinkette). On two occasions separated by a wash-out period of 1 week volunteers received a single oral dose of both formulations. On each administration day blood samples were collected at predetermined time points in order to investigate the pharmacokinetic parameters. Single oral doses of ranitidine were very well tolerated by healthy male volunteers. The non-parametric 95% confidence intervals for AUC and Cmax were 87 to 116% and 84 to 107%, respectively. The relative bioavailability of the ranitidine effervescent tablet was 99% compared to the dispersible tablet. The mean of the Cmax ratio was 95%. The ranitidine effervescent tablet could thus be claimed to be bioequivalent to the dispersible tablet. PMID- 1418074 TI - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin and the human lens. Clinical results of a 3-year follow-up. AB - Simavastatin (MK-733, Zocor, CAS 79902-63-9), a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was administered for a period of at least 3 years to 21 patients suffering from primary hypercholesterolemia. Significant decreases were noted for plasma cholesterol (30%), low density lipoprotein cholesterol (40%), whereas an increase in plasma high density lipoprotein cholesterol (11%) was observed. The drug therapy was well tolerated and clinical examinations revealed no adverse effects. No development of cataracts or other ocular side effects have been observed during this 3-year follow-up period. PMID- 1418075 TI - Interaction of spironolactone with mercury. A possible molecular mechanism. AB - The protective activity of spironolactone (CAS 52-01-7) against mercuric acetate intoxication and the action of a spironolactone-mercuric acetate complex were studied on female Sprague-Dawley rats. Spironolactone was given 30 min after the toxic agent. It was found that spironolactone reversed the toxic effects of mercury, the mercury-spironolactone complex was much less toxic than mercuric acetate and its toxicity disappeared with the administration of spironolactone. A molecular mechanism for the protective action of spironolactone against mercury intoxication is proposed. The presence of both the steroidal skeleton and the thioacetyl group in the same molecule is necessary for the protection against mercury intoxication. PMID- 1418076 TI - Nimesulide in the treatment of advanced cancer pain. Double-blind comparison with naproxen. AB - In a clinical double-blind study, the analgesic efficacy and the side-effects of nimesulide (Aulin, CAS 51803-78-2) and naproxen administered to 68 patients affected by advanced cancer pain were compared. Patients were treated with non steroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO. The dose administered was 200 mg b.i.d. (every 12 h) for nimesulide and 500 mg b.i.d. (every 12 h) for naproxen. From this study the analgesic effect and the tolerability of the two drugs appeared to be similar. Both drugs resulted to be effective with a low incidence of adverse events that may be related to their use. PMID- 1418077 TI - Effects of novel retinoids on growth and differentiation of a rhabdomyosarcoma cell line. AB - The influence of all-trans-retinoic acid-beta-D-glucopyranosylester, all-trans retinoic acid-beta-D-galactopyranosylester, methyl-(1-O-retinoyl-beta-D glucopyranoside)uronate and all trans-retinyl-beta-D-glucuronide were investigated on the celle line BA-HAN-1C. This clonal cell line was derived from a dimethylbenzanthracene induced rhabdomyosarcoma in the rat. The tumor cells were incubated for 5 days with medium which was supplemented with various concentrations of the different compounds. The action of the retinoids were measured by comparing the cellular growth and the creatine kinase activity (as differentiation marker) with an supplemented cell line. The retinoids which are based on all-trans-retinoic acid (all-trans-retinoic acid-beta-D glucopyranosylester, all-trans-retinoic acid-beta-D-galactopyranosylester, methyl (1-O-retinoyl-beta-D-glucopyranoide)uronate and their chemical precursors) showed similar biological effects as all-trans-retinoic acid and could be used in higher concentrations than retinoic acid without the appearance of toxic effects. The all-trans-retinyl-beta-D-glucuronide derivatives did not show any influence on the cell growth and their creatinine kinase activity. With respect to the effects of the compounds two hypothesis about their function were possible: They act as a whole molecule, or: they are bound to a receptor where the really effective substance, all-trans-retinoic acid is released from the molecule by hydrolytic cleavage as required. Investigations with the carbohydrates D-glucose, D galactose and D-uronic acid disproved the second theorie because these substances enormously support the growth of the tumor cells. The effectively of the free all trans-retinoic acid would have been diminished by these components. However, this effect did not appear if hydrolysis is considered. PMID- 1418078 TI - Fibrinogen and antithrombin III blood levels fluctuations during isoniazid or isoniazid plus rifampicin administration. AB - Nineteen randomized patients, treated with isoniazid (INH, CAS 54-85-3) for tuberculosis chemoprophylaxis or isoniazid plus rifampicin (RMP, CAS 13292-46-1) combination for tuberculosis therapy, were studied in order to explore the effects of these drugs on fibrinogen and antithrombin III blood levels. Other hepatic biology indices were also measured (aminotransferases, alkaline phosphatase, prothrombin time etc). The results suggested a relationship between INH or INH + RMP administration and fibrinogen as well as antithrombin III blood levels. The data indicate a protective effect of the RMP synchronous administration (by enzyme induction mechanisms) in the preservation of fibrinogen blood levels. PMID- 1418079 TI - Synthesis of some hydroxamic acid derivatives of benzimidazole and their antibacterial and antifungal activities. AB - A number of 1H-benzimidazole-2-propanoic acid derivatives have been synthesized by Phillips method, and their antibacterial and antifungal activities have been tested. The chemical structures of the synthesized compounds were elucidated by spectroscopic (IR, NMR, mass) and elementary analysis. Investigation of antimicrobial activity of the compounds was done by agar dilution technique using bacteria (Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Mycobacterium smegmatis ATCC 607) and yeast like fungi (Candida albicans, Candida tropicalis, Candida pseudotropicalis, Candida kruzei, Candida globrata). Among the compounds tested N-hydroxy-3-(1H benzimidazol-2-yl)-propionamide (Compound 6) showed considerable activity against both Candida albicans and Candida tropicalis. PMID- 1418080 TI - Subcellular distribution and antifungal effects of fluconazole in human phagocytic cells. Demonstration of the antifungal agent in neutrophil polymorphonuclear leucocytes and monocytes by autoradiography and electron micrography. AB - Electron microscopic autoradiography was used to demonstrate the presence of [3H] fluconazole (CAS 86386-73-4) in neutrophils and monocytes isolated from volunteers. Quantitative analysis of the autoradiographs showed significant accumulation of fluconazole in both phagocytic cells. The distribution of fluconazole was equal in the different intracellular compartments such as cytoplasm and nucleus. Fluconazole (20 micrograms/ml) induced ultrastructural changes in Candida albicans cells which had been phagocytized by neutrophils or monocytes (macrophages) in vitro. Particularly, changes in the plasma membrane and in the cytoplasmic structure of the intraphagocytic yeast cells were observed electron microscopically. PMID- 1418081 TI - Comparative assessment of the cytotoxic effects of different xenobiotics in three hepatoma cell lines. AB - MH1C1, HTC and HEPA 1c1c7 hepatoma cell lines were selected in this study as the bioindicators of the cytotoxicity induced by six chemicals: butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), cycloheximide (CHE), cyclophosphamide (CPA), potassium dichromate (Cr VI) and 2,4-dinitrophenol (DNP). The concentrations used were in the range from 10(-6) mol/l to 10(-2) mol/l, and the exposure time was 24 h. Two end-points were measured to evaluate cytotoxicity: the detachment of dead cells from the monolayer (CS), as evaluated by detection of the total macromolecules present in the cell monolayers solubilized in alkali and the loss of colony-forming efficiency (CF). The dose response curves were different from one compound to another, but generally similar with the two assays, the colony formation being the most sensitive test. Some technical problems like the toxicity of the solvents at the highest concentrations, the different sizes of colonies, the unspecific cellular detachment due to overgrowth during the experimental time, can be overcome by accurate standardization of the protocols used for each cell line. The sensitivity of the three cell lines was very similar, with some differences in the case of compounds exerting intermediate toxic effects, like CHE and DNP. The most toxic compound was Cr (VI), the least toxic one was CPA. The low cytotoxic effects displayed by CPA could be due to a lack of bioactivation and/or an increase of the inactivating enzymes, which are typical of hepatoma cell lines. PMID- 1418082 TI - Effect of acetylsalicylic acid, ascorbate and ibuprofen on the macrophage system. AB - The influence of ascorbic acid (CAS 50-81-7), acetylsalicylic acid (CAS 50-78-2) and ibuprofen (CAS 15687-27-1) on macrophages of C57BL/6 mice was investigated in vitro. It has been shown that ascorbic acid or acetylsalicylic acid alone did not stimulate or inhibit the production of interleukin-6, whereas a combination of both substances caused a significant stimulation. The viral replication in L929 fibroblasts was not affected by ascorbate and/or acetylsalicylic acid. In addition, the tumor-necrosis factor (TNF) synthesis of peritoneal macrophages was neither stimulated nor inhibited by both substances, alone or in combination. The oxygen radical production, however, was definitely inhibited by ascorbic acid, the effect of acetylsalicylic acid was far less marked, but at the high concentrations the inhibition was clearly discernible. Ibuprofen, a propionic acid derivate, was able to reduce the replication of vesicular stomatitis virus in L929 fibroblast cells. At the highest concentration of ibuprofen, 100 micrograms/ml, 34% of the fibroblast were able to survive. This protective effect declined as the ibuprofen concentration decreased. Ibuprofen could not stimulate peritoneal macrophages to secrete TNF, whereas the oxygen radical production was significantly reduced. In addition, ibuprofen activated mouse macrophages to produce interleukin-6 in a dose dependent way. The results of the in vitro experiments presented clearly show that ascorbic acid, acetylsalicylic acid in ibuprofen influenced the unspecific immune system. PMID- 1418083 TI - Coumarin congeners as antidepressants. AB - 3-Carboethyl coumarin (I) was converted to coumarin 3-acid hydrazide (II). This on reaction with appropriate aldehyde yielded 3-arylidino amino coumarin (III). Compound III on diazotisation and reaction with ferric chloride yielded the corresponding formazans viz. 3-substituted phenyl azoarylidino, amido coumarins (IVa1-a10) and oxadiazoles viz. 2-aryl-5-(3-coumarinyl)-1,3,4-oxadiazoles (Va1 a3), respectively. Simultaneously 3-carboethyl coumarin on hydrolysis gave 3 carboxy coumarin (VI) which on reaction with aryl amine in methylene chloride yielded 3-(N-aryl)amido coumarin (VIIa1-a3). The compounds were screened for their antidepressant activity against a tricyclic antidepressant (imipramine). Compounds IVa4, IVa5 and IVa9 exhibited activity better than imipramine with no toxicity (ALD50 greater than 1000 mg/kg) but IVa5 showed some side effects. PMID- 1418084 TI - Inotropic and chronotropic effect of glycerol formal on the isolated rabbit heart. AB - Glycerol formal (CAS 5464-28-8), an organic solvent used to vehicle drugs to target cells, has been shown to possess its own toxicopharmacological properties. The present work was undertaken to study its direct effect on the isolated rabbit heart. At 2.3 and 4.6 mmol/l (bolus) glycerol formal exerted a positive inotropic effect. Upon a perfusion of 4.5 mmol/l/h, the left ventricular pressure and the coronary flow were increased, while at 11 mmol/l/h these two parameters showed a tendency to decrease. Glycerol formal upon a perfusion at 11 mmol/l/h decreased mildly the positive inotropic effect of noradrenaline, and strongly that produced by acetylcholine at a nicotinic dose, while it accentuated the bradycardia induced by acetylcholine at a muscarinic dose. On the contrary it potentiated the stimulant effect of nicotine. The positive inotropic effects of tyramine, dimethylphenylpiperazinium and potassium chloride were decreased showing an inhibition of noradrenaline liberation induced by glycerol formal at the doses used. The action of glycerol formal on agents inducing a positive inotropic effect, except nicotine, and its cardiodepressant effect are probably partly due to its action on the Ca2+ ion. PMID- 1418085 TI - American Speech-Language-Hearing Association. 1992 annual convention. San Antonio, Texas, November 20-23, 1992. Program and abstracts. PMID- 1418086 TI - The status of PAI-1 as a risk factor for arterial and thrombotic disease: a review. AB - Plasminogen activator inhibitor-1 (PAI-1) is a rapid inhibitor of tissue plasminogen (tPA) in vivo. Evidence suggests that the level of plasma PAI-1 activity is responsible for the regulation of the whole fibrinolytic process through this tPA/PAI-1 interaction. Levels of PAI-1 have therefore emerged as a candidate for a thrombotic risk factor. Recent epidemiological data supports the view that high plasma levels of PAI-1 may be important in the pathogenesis of arterial and thrombotic disease. These data are reviewed and their significance discussed. PAI-1 expression has been shown to be regulated by many different factors in vitro and the relevance of these data to in vivo physiology is addressed. The current knowledge of the biochemistry, expression and genetics of PAI-1 is also presented and the significance of this to disease pathogenesis is discussed. PMID- 1418087 TI - Lipolysis of triglyceride-rich lipoproteins activates coagulant factor XII: a study in familial lipoprotein-lipase deficiency. AB - A high factor VII coagulant activity (VIIc), a marker of increased risk of coronary heart disease, is frequently found in types IIb and IV hyperlipidaemia, but its cause is not fully understood. Factor VII can be activated by factor XIIa, generated from factor XII upon activation of the contact system of coagulation. Ten patients with familial lipoprotein-lipase (LPL) deficiency and 10 healthy control subjects were therefore compared to explore the hypothesis that high concentrations of unesterified fatty acids (UFA), released from triglyceride-rich lipoproteins by LPL, are a source of factor XII activation and hence the increased VIIc that is observed post-prandially and in non-LPL deficient hypertriglyceridaemic states. Mean plasma cholesterol and triglyceride concentrations were, respectively, 1.5- and 19-fold higher in the patients than controls, due to increases in very-low-density lipoproteins and chylomicrons. The concentration and composition of plasma UFA were similar in both groups. In conformity with the hypothesis, VIIc was not increased in the LPL-deficient group, despite their massive hypertriglyceridaemia. Furthermore, when the patients' plasma was treated with LPL, factor XII was activated promptly and substantially, whereas no similar effect was observed in the controls. These results suggest that high concentrations of circulating triglyceride-rich lipoproteins will increase VIIc in the presence of LPL. PMID- 1418088 TI - Experimental induction of atherosclerosis associated with femoral arteriovenous fistulae in rabbits on a stock diet. AB - Chronic femoral arteriovenous fistulae were surgically produced in stock-fed rabbits. The aortic bifurcation and branching sites of the ilio-femoral arteries from each side were examined histologically by the serial section technique in rabbits killed at varying times from 121 to 800 days postoperatively. Similar preparations were examined from old multiparous breeding does and rabbits with a control femoral arteriotomy. Tears of the internal elastic lamina were prominent in the abdominal aorta and homolateral ilio-femoral arteries of those with fistulae but were only occasional and sporadic in contralateral arteries and control animals. Intimal proliferation at branching sites proximal to the fistula exhibited varying degrees of enlargement, extension and progression to overt atherosclerosis with lipid accumulation, fibrin deposition and calcification. Such changes were minimal proximally in contralateral vessels of a few rabbits and non-existent in control material. These results (i) constitute the first experimental induction of the progression of intimal proliferation to overt atherosclerosis at branching sites in stock-fed animals and (ii) substantiate the importance of haemodynamics in atherogenesis. PMID- 1418089 TI - Effect of sucrose diet on expression of apolipoprotein genes A-I, C-III and A-IV in rat liver. AB - A sucrose-rich diet stimulates hepatic lipogenesis and induces net production of very low density lipoproteins in the liver. To study changes of hepatic apolipoprotein gene expression in response to such a diet, we measured the mRNA abundance of apolipoproteins A-I, C-III and A-IV in livers of rats fed a sucrose rich diet or a control diet for 3 weeks. In livers of sucrose-fed rats, the abundance of cellular and nuclear apo A-IV mRNA increased to 185% +/- 21% and 142% +/- 22% of control values (P less than 0.01), respectively. In sucrose-fed rats, the transcriptional activity of the apo A-IV gene, measured in a cell-free transcription system using isolated liver nuclei, increased to 144% +/- 23% of control (P less than 0.05). In contrast, this diet neither affected the abundance of cellular and nuclear apo A-I and apo C-III mRNA nor the transcriptional activity of these genes in liver. These results are consistent with specialization of the regulatory elements of the genes coding for apolipoproteins A-I, C-III and A-IV. Alternatively, enhanced transcription of the apo A-IV gene may preclude increased synthesis of apo A-I and/or apo C-III mRNA due to the close linkage of the three genes in the rat genome. PMID- 1418090 TI - Apolipoprotein A-I and apolipoprotein B containing lipoprotein particles in coronary patients treated with extracorporal low density lipoprotein precipitation (HELP). AB - Evidence for chemical and biological heterogeneity of human plasma lipoprotein density classes has been steadily accumulating over the last 15 years. Furthermore, several recent reports have indicated potential clinical significance of certain lipoprotein subspecies as either atherogenic or antiatherogenic. It is generally accepted that lipid lowering treatments can retard or even reverse development of atherosclerotic lesions. However, very little is known about effects of various lipid lowering treatments on specific lipoprotein particles. The purpose of this study was to explore the effects of heparin induced extracorporal low density lipoprotein precipitation (HELP) on various subspecies of plasma lipoprotein particles defined primarily by their apolipoprotein composition. Using particle specific enzyme immunoassays, the immediate changes in lipoprotein particle profiles were analyzed after a single HELP treatment in 12 patients with angiographically documented coronary artery disease. In a separate group of 6 patients, particles were repeatedly measured over a period of 96 h following a HELP treatment. Single HELP treatment caused an immediate and highly significant decrease (67%) in the concentration of simple lipoprotein particles containing apolipoprotein B (apo B) as a sole apolipoprotein (LP-B). Various subspecies of complex particles containing apo B and other apolipoproteins (Lp-B-complex) were also decreased although to a lesser degree (44-53%). HELP treatment caused an insignificant, 3% decrease of lipoprotein particles containing apo A-I but no apo A-II (Lp-A-I) and a 6% decrease in the concentration of particles containing both apo A-I and apo A-II (Lp-A-I:A-II). During the 96-h period following HELP treatment various apo B containing particles recovered at different rates in different patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1418091 TI - Hypercholesterolaemia alters arterial and blood factors related to atherosclerosis in hypertension. AB - To evaluate the influence of hypercholesterolaemia on arterial and blood factors related to cardiovascular disease in hypertension, 20 normocholesterolaemic and 31 hypercholesterolaemic hypertensive patients underwent determinations of whole blood filterability (WBF), plasma fibrinogen concentration (PF) and aortic pulse wave velocity (PWV). Both of the groups had similar age, body mass index, cumulative smoking dose and blood pressure. Hypercholesterolaemics had lower WBF (P less than 0.02), higher PF (P less than 0.02) and higher PWV (P less than 0.01) than normocholesterolaemics. In the whole population WBF correlated with age (P less than 0.005), mean blood pressure (P less than 0.01), total cholesterol (P less than 0.05) and plasma fibrinogen (P less than 0.01). However, in a multivariate analysis where age and pressure were controlled as variables, only the association between WBF and PF remained significant (P less than 0.001). Thus, the higher fibrinogen affects whole blood filterability in hypercholesterolaemic hypertensive patients. In the whole population PWV correlated positively with HDL cholesterol (P less than 0.01) and age (P less than 0.001) and the association with HDL cholesterol remained significant in a multivariate analysis (P less than 0.001) where age was controlled. The effect of ageing on arterial rigidity seems to be similar in both hypertensive groups as deduced from the identical regression slopes relating pulse wave velocity to age. So in hypertension with high cholesterol, arterial rigidity was increased without changes in arterial stiffening with age. PMID- 1418092 TI - Short-term interruption of training affects both fasting and post-prandial lipoproteins. AB - Exercise training alters plasma lipoprotein profiles in a manner compatible with decreased coronary artery disease risk. The aim of this study was to ascertain whether interruption of training (detraining) was associated with potentially undesirable changes in the metabolism of post-prandial lipoproteins and plasma levels of Lp(a). Eight normolipidemic, male runners who ran 30-40 miles/week were studied in the trained state and after 14-22 days of detraining. Two of the subjects were studied in the reverse order to control for any confounding effects of exercise sequence. Detraining resulted in (1) a 12% (P = 0.002) reduction in the subjects' aerobic capacity, (2) a 7.7% (P = 0.007) reduction in fasting concentrations of high density lipoprotein cholesterol (HDL-C), (3) a 21% (P = 0.01) reduction in post-heparin lipoprotein lipase activity. Lp(a) concentrations did not change significantly (mean increase 15%, P = 0.076). Fasting plasma concentrations of total cholesterol (TC), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C) did not change in the detrained state. There was little fluctuation over 24 h in plasma concentrations of TC, LDL-C and HDL-C in either the trained or detrained states. TG concentrations fluctuated over the 24 h in accord with food intake, but there were no exercise-related changes. Exercise had a dramatic effect on chylomicron and chylomicron remnant metabolism as measured by retinyl palmitate measurements. The mean areas under the concentration vs. time curves (AUC) for chylomicron-retinyl esters increased by 41% (P = 0.013) and for chylomicron remnant-retinyl ester by 37% (P = 0.058) following detraining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418093 TI - Long-term treatment of neonatal aortic smooth muscle cells with beta VLDL induces cholesterol accumulation. AB - A model for smooth muscle derived foam cells was developed by treating smooth muscle cells isolated from the aortae of neonatal rabbits with beta VLDL for up to 1 month. Hyperlipidemic beta VLDL isolated from cholesterol fed rabbits induced proliferation of the cells that were maintained in lipid deficient serum. In addition, the lipoprotein fraction stimulated [14C]oleic acid incorporation into [14C]cholesteryl ester, even in cultures that had been chronically exposed to the lipoprotein. The accumulation of cholesterol was evaluated and small amounts of cholesteryl ester were demonstrated in cultures treated for 3 days with beta VLDL. However, continued exposure to the lipoprotein resulted in larger elevations in total cholesterol, approximately 65% of which was in the esterified form in cultures treated with 100 micrograms beta VLDL/ml for 24 days. When cholesterol levels were examined as a function of time, it was determined that both total cholesterol and cholesteryl ester levels increased. Approximately 2-3 weeks after lipoprotein was introduced to the culture, maximum levels were attained. Triglyceride levels were also measured and found to increase more than two-fold in cultures that had been incubated in the presence of beta VLDL for 24 days, when compared to cultures incubated in its absence. Examination of the cultures by electron microscopy revealed intracytoplasmic lipid droplets in beta VLDL treated cells. These results suggest that beta VLDL treatment of neonatal aortic smooth muscle cells provides an ideal model in which to study the lipid laden smooth muscle cells that characterize the atherosclerotic plaque. PMID- 1418094 TI - Activation of leukocytes with complement C5a is associated with prostanoid dependent constriction of large arteries in atherosclerotic monkeys in vivo. AB - Activated leukocytes release a variety of substances which have been shown in vitro to modulate vascular tone. The chemotactic peptide complement C5a is a physiological activator of leukocytes. We injected human recombinant complement C5a (10 and 100 micrograms) into the blood-perfused hind limb of normal and atherosclerotic cynomolgus monkeys and examined vascular responses. In both normal and atherosclerotic monkeys, the high dose of C5a produced about 65% decrease in leukocyte cell count in venous blood drainage from the hind limb. Injection of C5a produced a pronounced increase in resistance of large arteries (segment from iliac artery to dorsal pedal artery) in atherosclerotic, but not in normal monkeys. The constrictor effect of C5a in atherosclerotic monkeys was abolished by the thromboxane A2 receptor antagonist SQ 29,548 (2 mg/kg i.v.). The platelet-activating factor antagonist WEB 2086 (5 mg/kg, i.v.) did not alter vascular responses to C5a. We conclude that activation of leukocytes produces constriction of large arteries in atherosclerotic, but not normal, monkeys in vivo. This response may be mediated in part by release of thromboxane A2. PMID- 1418095 TI - Lipoprotein risk factors in vegetarian women of Indian descent are unrelated to dietary intake. AB - Dietary intakes, anthropometric indices and plasma lipoprotein and alpha tocopherol concentrations were measured in premenopausal vegetarian women of Indian descent (n = 22) and in white women of European descent consuming either mixed (n = 22) or vegetarian diets (n = 18). The Indian women were shorter in height than the white women and had a higher proportion of body fat. Energy intakes were lower in the Indian women, both in absolute terms and per kg body weight. The proportion of energy derived from saturated fatty acids was lower and that from polyunsaturated fatty acids was greater in both Indian and white vegetarians compared with the subjects on mixed diets. Intakes of dietary fibre and vitamins C and E were higher in the white vegetarians compared with the other groups. Plasma concentrations of total and LDL cholesterol and apolipoprotein B and the ratio of apolipoprotein B/apolipoprotein AI were lower and HDL and HDL2 cholesterol, alpha-tocopherol concentrations and the ratio of alpha tocopherol/cholesterol were greater in the white vegetarian group than in the other groups. Total plasma cholesterol was associated with measures of truncal obesity, especially subscapular skinfold thickness and the percentage energy derived from saturated fatty acids. Plasma concentrations of apo(a) were higher and those of HDL and HDL2 cholesterol and sex hormone binding globulin (SHBG) were lower in the Indian vegetarian women compared with both groups of white women. No relationship could be found between apo(a), HDL and HDL2 cholesterol concentration and nutrient intake but HDL and HDL2 were negatively associated with the proportion of body fat and apo(a) weakly with subscapular skinfold thickness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418096 TI - Effective reduction of plasma LDL levels by LDL apheresis in familial defective apolipoprotein B-100. AB - The clinical response to long-term reduction of the plasma LDL cholesterol concentration was studied in a man with severe coronary artery disease associated with familial defective apolipoprotein B-100 (FDB). Plasma exchange repeated at 2 week intervals, combined with lipid-lowering drugs, led to remission of angina and improved exercise test performance. A similar clinical response was achieved after LDL apheresis with dextran sulphate columns repeated once every 2 weeks in combination with drug treatment. The reduction in plasma LDL cholesterol level brought about by LDL apheresis was at least as marked in the FDB patient as in 5 patients with familial hypercholesterolaemia. We conclude that FDB patients with coronary artery disease may derive clinical benefit from prolonged reduction of their plasma cholesterol levels and that LDL containing apo B-100 in which arginine at position 3500 is replaced by glutamine is removed from plasma by dextran sulphate columns as efficiently as is normal LDL. PMID- 1418097 TI - Disruption of endothelial barrier function by lipolytic remnants of triglyceride rich lipoproteins. AB - Remnants, resulting from the lipolysis of triglyceride-rich lipoproteins, injured cultured endothelial cells and resulted in decreased barrier function of the vascular endothelium. Endothelial cells were cultured on micropore filters. Albumin transfer across endothelial cell monolayers was measured after a 24-h exposure to media enriched with control or in vitro-lipolyzed samples of various hypertriglyceridemic (HTG) sera and its isolated lipoprotein (VLDL, LDL and HDL) and serum free protein (d greater than 1.21 g/ml) fractions. Compared with control cultures, neither control HTG serum nor its isolated lipoprotein and serum-free protein fractions had any effect on albumin transfer. In contrast, lipolyzed HTG (L-HTG) serum and all of its isolated lipoprotein fractions (L VLDL, L-IDL, L-LDL and L-HDL) caused a marked decrease in endothelial barrier function, evidenced by a significant increase in albumin transfer across endothelial monolayers. The L-IDL and L-HDL fractions were more effective in increasing albumin transfer than the L-VLDL and L-LDL fractions. The extent of the L-IDL and L-HDL mediated increases in albumin transfer was concentration dependent. An exposure of 12 h was required for L-HDL to increase albumin transfer. The L-HDL mediated increase in albumin transfer was reversible only after a 12-h exposure at low concentrations. The free protein fraction from L-HTG serum had no significant effect on the barrier function of endothelial cells. The presence of normolipidemic HDL in culture medium prevented disruption of the endothelial barrier induced by L-IDL but not by L-HDL. The decrease in endothelial barrier function induced by lipolyzed samples of HTG serum or lipoproteins appeared to be correlated with the level of free fatty acids contained in lipolytic remnants. Enrichment of LDL, and in particular HDL, with fatty acid significantly increased albumin transfer. Compared with lipolyzed samples, sera/lipoproteins oxidized in vitro by Cu2+ ions had little effect on endothelial barrier function, which did not correlate with their respective thiobarbituric acid-reacting substance (TBARS) values. TBARS remained within normal range after L-HDL incubation with endothelial cells for up to 48 h. At most concentrations tested, exposure to lipolyzed but not oxidized lipoproteins resulted in morphological perturbations of cell monolayers. These data suggest that lipolytic remnants of triglyceride-rich lipoproteins may play an important role in the development of atherosclerosis by decreasing the barrier function of the vascular endothelium. The remnant-induced injury of the arterial wall may permit the entry of cholesterol-rich lipolytic remnants as well as LDL into the arterial wall. PMID- 1418098 TI - Studies on apolipoprotein(a) phenotypes. Part 1. Phenotype frequencies in a healthy Japanese population. AB - The frequency distribution for serum lipoprotein(a) (Lp(a)) concentrations in healthy Japanese was highly skewed, with a mean +/- S.D. of 14.6 +/- 13.6 mg/dl and a median of 11.0 mg/dl. The present study provides the first evidence on the frequencies of Lp(a) phenotypes and alleles in healthy Japanese subjects. There was a strong inverse relationship between the apparent molecular weights of apo(a) isoforms and plasma Lp(a) concentrations, as reported previously. However, because of the considerable overlap between the Lp(a) concentrations of the different phenotypes, it was impossible to predict Lp(a) concentration from Lp(a) phenotypes, or vice versa. The present results suggest that the distribution of Lp(a) concentrations, mean and median values and Lp(a) phenotype and allele frequencies in healthy Japanese are not significantly different from the results for Europeans, whereas they are significantly different from other Asian populations, i.e. Chinese, Indians and Malaysians. PMID- 1418099 TI - The effect of concurrent administration of isradipine on the development of fatty streaks in the cholesterol-fed rabbit: a morphometric study. AB - Calcium antagonists attenuate the development of aortic lesions in cholesterol fed rabbits. This study was undertaken to examine the influence of isradipine (dose: 0.3 mg/kg per day orally) on the histological components of these lesions in New Zealand White rabbits (age: 12 weeks, weight: 2-2.5 kg). Five groups of animals were fed standard chow with the following supplements for 3 weeks: Group 1, no supplements; Group 2, 40 g cholesterol; Group 3, 60 g cholesterol; Group 4, 40 g cholesterol + isradipine; Group 5, 60 g cholesterol + isradipine. After 3 weeks, the animals were killed and the aorta prepared for morphometry. The volume of intima/cm aorta was estimated and the volume fraction (Vv) of the intima occupied by components of the lesions was estimated by point counting. By integrating these two measurements the volume/unit length (mm3/cm) of the following components of the aorta were estimated: intima, non-cellular components, endothelial cells, myointimal cells, lipid accumulating myointimal cells and foam cells. Cholesterol feeding for 3 weeks was associated with significant increases in the volume of non-cellular components of the intima, endothelial cells, myointimal cells, lipid accumulating myointimal cells and foam cells. Administration of isradipine significantly reduced all these parameters. It is concluded that isradipine attenuates cellular hyperplasia and accumulation of non-cellular components of lesions in cholesterol fed rabbits. PMID- 1418100 TI - Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males. AB - Whether an association, causative or not, exists between the level of serum selenium and the risk of ischaemic heart disease (IHD) remains unsettled. We investigated the issue in a cohort of 3387 males aged 53-74 years (mean 63). Based on information about health status, life-style and socioeconomic factors given in a prefilled comprehensive questionnaire, the men were interviewed and the information validated. Following the interview, they underwent a clinical examination and had a venous blood sample drawn for the determination of a number of biochemical characteristics. Three hundred and forty-six men were excluded due to prevalent cardiovascular disease, including stroke. During the next three years (1986-1989) 107 men (approximately 3%) suffered an IHD event; 25 events were fatal. Compared to others, men with serum selenium levels less than or equal to 1 mumol/l, approximately the lowest tertile, had a 70% increased risk of IHD, relative risk (RR) with 95% confidence limits was 1.70 (1.14-2.53). After multivariate adjustment for cholesterol, social class, smoking and age, RR was 1.55 (1.00-2.39). Serum selenium level was significantly (P less than 0.05), but not strongly, correlated with a number of IHD risk factors: serum cotinine, tobacco smoking, social class, alcohol consumption, total cholesterol, hypertension, age and physical inactivity. Body mass index, HDL-cholesterol and triglycerides were not significantly associated with serum selenium. We conclude that middle-aged and elderly Danish men with serum selenium less than or equal to 1 mumol/l had a significantly increased risk of ischaemic heart disease. This association was not explained by the interrelationship of serum selenium and major cardiovascular risk factors. PMID- 1418101 TI - Inheritability of atherosclerosis and the role of lipoproteins as risk factors in the development of atherosclerosis in WHHL rabbits: risk factors related to coronary atherosclerosis are different from those related to aortic atherosclerosis. AB - Inheritability of atherosclerosis and the influences of serum lipids on atherosclerosis were examined by following its progression in selectively bred WHHL rabbits. Our studies indicate (1) coronary atherosclerosis is clearly inherited from parents by offspring whereas inheritability of aortic atherosclerosis is uncertain; (2) coronary stenosis is positively correlated to serum cholesterol level, although the correlation coefficient is markedly low: in contrast, no relationship between serum lipid levels and aortic atherosclerosis was observed; (3) cholesterol-rich VLDL showed atherogenicity in aorta, but not in coronary arteries; (4) an unknown lipoprotein detected by 3.6% polyacrylamide gel electrophoresis was related to coronary atherosclerosis, although no relationship between the unknown lipoprotein and aortic atherosclerosis was observed. These findings suggest that there are two types of genetic factors involved in atherosclerosis, one of which is unique to coronary atherosclerosis whereas the other is related to only aortic atherosclerosis. PMID- 1418102 TI - Comparative hypolipidemic effects of lovastatin and simvastatin in patients with heterozygous familial hypercholesterolemia. AB - We have compared the effects of lovastatin and simvastatin on plasma lipoproteins, fibrinogen and urinary mevalonic acid excretion in twenty-three patients with heterozygous familial hypercholesterolemia. After a baseline period patients were randomly assigned to receive lovastatin or simvastatin at doses of 10, 20 and 40 mg twice daily, for a period of 2 months each, and then, after a 4 week wash-out period, all patients received the alternate drug for a similar period of therapy. Both drugs were well-tolerated and no patients were withdrawn due to side effects. Lipid values returned to baseline after discontinuation of therapy and no carry-over effect was observed. Treatment with lovastatin resulted in decreases in LDL cholesterol concentrations from 274 mg/dl at baseline to 211, 192 and 178 mg/dl, respectively, on doses of 20, 40 and 80 mg/day. Treatment with simvastatin reduced concentrations of LDL cholesterol to 194, 168 and 156 mg/dl, respectively, on doses of 20, 40 and 80 mg/day. Concentrations of HDL cholesterol increased on both drugs, but no dose response relationship was apparent. Both drugs reduced the 24-h urinary excretion of mevalonic acid, an intermediate in cholesterol biosynthesis, but the magnitude of decrease was similar with lovastatin and simvastatin. Small, but statistically non-significant decreases in fibrinogen occurred with both drugs. Patients who showed the greatest hypolipidemic effect during treatment with lovastatin also showed an excellent therapeutic response to simvastatin and vice versa. We conclude that, on a milligram per milligram basis, simvastatin is twice as potent as lovastatin in the treatment of familial hypercholesterolemia and that with both drugs, reductions in LDL cholesterol concentrations are accompanied by decreases in the urinary excretion of mevalonic acid. PMID- 1418103 TI - Impaired left ventricular relaxation and hyperinsulinemia in patients with primary hypercholesterolemia. AB - Fifteen non-obese patients with familial hypercholesterolemia and fifteen normocholesterolemic subjects matched for age, body mass index, waist/hip ratio, arterial blood pressure and sedentary life style underwent blood sampling for determination of fasting plasma glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides, free fatty acids, apolipoprotein A1 and B. In both groups of subjects we determined erythrocyte membrane microviscosity and performed an echocardiographic study. We demonstrated that hypercholesterolemic patients had a significant increase in fasting plasma total cholesterol (8.9 +/- 0.5 vs. 5.5 +/- 0.3 mmol/l, P less than 0.001), insulin (79 +/- 4 vs. 58 +/- 4 pmol/l, P less than 0.05) and apolipoprotein B (2.2 +/- 0.5 vs. 1.3 +/- 0.5 g/l P less than 0.01). In the echocardiographic study we found a significant impairment in left ventricular relaxation (isovolumic relaxation time (IRT) 106 +/- 6 vs. 73 +/- 7 ms, P less than 0.01). Erythrocyte membrane microviscosity (0.253 +/- 0.004 vs. 0.225 +/- 0.003, P less than 0.05) was also increased in hypercholesterolemic patients. Finally we found that erythrocyte membrane microviscosity correlated with fasting plasma insulin levels (r = -0.46, P less than 0.03) and IRT (r = 0.52, P less than 0.01). PMID- 1418104 TI - Collagen types I and III, collagen content, GAGs and mechanical strength of human atherosclerotic plaque caps: span-wise variations. AB - Measurements of total collagen, of the ratio of collagen types III/(I+III) and of sulphated glycosaminoglycans (GAGs) were compared with mechanical strength for individual ulcerated and non-ulcerated human aortic plaque caps and with intima adjacent to the plaques. The distributions of the collagen type ratio were similar for both ulcerated and non-ulcerated plaque caps but different from that of the adjacent intima. The proportions of different collagen types were not related to fracture stress and are thus unlikely to affect the potential to ulcerate. The distributions of the sulphated GAGs showed lower amounts for the plaque caps compared with the nearby intima, with the centres of ulcerated plaque caps having the lowest values. Total collagen had higher values in the peripheries of plaque caps compared with the nearby intima, but was distinctly lower in the centres of ulcerated plaque caps. Plaque caps appeared to require a higher collagen content than adjacent intima to support a given level of mechanical strength, suggesting that while collagen production had occurred in the plaque caps it was not as efficiently organized to resist fracture as a similar amount of collagen in the adjacent intima. Ulcerated plaque caps are notable for much larger transverse (centre vs. periphery) gradients of connective tissue constituents than for non-ulcerated plaque caps. The development of these transverse gradients may be a critical aspect in determining the propensity of a plaque to ulcerate. PMID- 1418105 TI - Compound heterozygote of cholesteryl-ester transfer protein deficiency in a patient with hyperalphalipoproteinemia. PMID- 1418106 TI - Studies on apolipoprotein(a) phenotypes. Part 2. Phenotype frequencies and Lp(a) concentrations in different phenotypes in patients with angiographically defined coronary artery diseases. AB - In the present paper, we have evaluated serum Lp(a) concentrations, the frequencies of Lp(a) phenotypes and alleles and the association between the Lp(a) phenotypes and serum Lp(a) levels in 470 patients with angiographically defined coronary artery disease (CAD). Serum Lp(a) concentrations were significantly increased in proportion to the number of diseased vessels in the CAD patients. The frequencies of Lp(a) phenotypes in the CAD patients were significantly different from those in healthy subjects. In particular, the frequency of double band phenotypes was higher in the CAD group. The frequencies of Lp(a) alleles in the CAD patients, however, were not significantly different from those in the healthy subjects. There was a strong inverse relationship between the apparent molecular weights of apo(a) isoforms and serum Lp(a) concentrations. Lp(a) levels in the CAD patients were higher than those in the healthy subjects with the same phenotype. The present results suggest that it is important to consider some posttranslational or environmental modifications and other factors, in addition to the genetic factor, when assessing contributions to plasma Lp(a) levels. PMID- 1418107 TI - A pharmacologist's opinion--alcoholism: the disease debate needs to stop. PMID- 1418108 TI - Influence of the level of dietary ethanol in mice with murine AIDS on resistance to Streptococcus pneumoniae. AB - Chronic ethanol consumption impairs cellular immune functions. This may explain the increased occurrence of various opportunistic infections in heavy ethanol users. Immunological alterations associated with Acquired Immune Deficiency Syndrome (AIDS) also permit more opportunistic infections. In this study, we used a murine model of retrovirus infection induced by LP-BM5 murine leukemia virus. The combined effects of ethanol use and early retroviral infection (prior to the development of AIDS) on resistance to Streptococcus pneumoniae were investigated. Consumption of ethanol by non-retrovirus-infected mice resulted in decreased resistance to S. pneumoniae. However, retrovirus-infected mice fed a diet containing high concentrations of ethanol (6 and 7% v/v) exhibited a greater resistance to S. pneumoniae infection than retrovirus-infected mice fed diets with lower concentrations (5%) or no ethanol. The total number of white blood cells also decreased as serum ethanol levels increased. There were also fewer lymphocytes and more neutrophils and monocytes in retrovirus-infected mice fed ethanol. Diet consumption decreased as the concentration of ethanol increased in the diet. Consumption was dependent upon the dark-light cycle. The highest diet consumption was observed during the first 4 hr of the dark period. The level of ethanol in serum was influenced by the amount of the diet consumed and its ethanol concentration. Both retrovirus infection and ethanol consumption effected survival after S. pneumoniae infection. PMID- 1418109 TI - Alcohol consumption and biological markers for alcoholism in idiopathic dilated cardiomyopathy: a case-controlled study. AB - The aim of this study was to compare alcohol consumption and biological markers for alcoholism in a population of 23 men (57 +/- 8 years) admitted to hospital with idiopathic dilated cardiomyopathy (DCM), and a control group of 46 men (54 +/- 8 years) with coronary artery disease, matched for age. The DCM group had a higher daily alcohol consumption (82 g/day vs. 30 g/day, P < 0.0002). This difference was greater for the consumption of wine (63 g/day in the DCM group vs. 24 g/day in the control group, P < 0.002). Duration of regular daily alcohol consumption was longer in DCM patients (34 years vs. 22 years, P < 0.01) as well as duration of heavy alcohol consumption (> 60 g/day) (25 years vs. 10 years, P < 0.001). Among the biological markers, only the serum levels of immunoglobulin A were significantly increased in the DCM group (3.7 g/l vs. 2.7 g/l, P < 0.03). In this French population, alcohol is strongly linked to DCM. Biological markers appear to be poor predictors of alcohol intoxication in this so-called 'idiopathic' myocardial disease. PMID- 1418110 TI - The antioxidant status of patients with either alcohol-induced liver damage or myopathy. AB - The antioxidant status of alcoholic patients was assessed by direct measurement of the plasma antioxidants alpha-tocopherol and beta-carotene and of selenium as a marker of glutathione peroxidase. Overall, the alcoholic group showed significant decreases in the mean plasma values of beta-carotene, zinc and selenium when compared to the control subjects. When the patients were subdivided according to their liver histology, beta-carotene showed a progressive decrease in plasma concentration with increasing liver damage, whereas alpha-tocopherol levels were only depleted in the patients with cirrhosis. There were significant decreases in the plasma concentrations of both alpha-tocopherol and selenium in all patients with alcoholic skeletal muscle myopathy, whereas patients with normal muscle biopsies showed adequate antioxidant status. Such results support a role for free radical-mediated damage in end organ injury, particularly myopathy, in alcohol misusers. PMID- 1418111 TI - Influence of acetaldehyde on the vasopressor effect of serotonin in pithed rats. AB - In pithed rats, the intravenous (i.v.) administration of serotonin (3, 10, 30, 100, 300 and 1000 micrograms/kg) produced a dose-dependent increase in blood pressure. The pressor response to serotonin was reduced by acute acetaldehyde administration in a dose of 30 mg/kg i.v. and by 5-HT2 antagonist ketanserin (0.03 mg/kg i.v.). However, the lowest doses of acetaldehyde (10 and 20 mg/kg) were ineffective. In in vitro studies we also demonstrated that acetaldehyde (0.43 mM/l) and ketanserin (0.1 microM/l) inhibited the serotonin-induced vasoconstriction of isolated rat tail artery. In both experimental models the combination of acetaldehyde with ketanserin decreased the action of serotonin to the same extent as did ketanserin alone. In pithed rats pretreated with a high dose of ketanserin (3 mg/kg i.v.) serotonin produced hypotension by stimulation of 5-HT1 receptors. This effect was not enhanced by acetaldehyde (30 mg/kg) injection. Our data suggested that the action of acetaldehyde on the effects of serotonin in pithed rats was non-specific and independent of its interaction with serotonergic 5-HT1 and 5-HT2 receptors in blood vessels. PMID- 1418112 TI - Attenuation of the behavioural effects of ethanol in mice by des-enkephalin-gamma endorphin (ORG 5878). AB - This study shows inhibition of the increase in locomotor activity induced by ethanol (2 g/kg i.p.) in mice by a low dose (0.1 mg/kg i.p.) of the non-opioid beta-endorphin fragment ORG 5878 (des-enkephalin-gamma-endorphin). ORG 5878 (0.1 mg/kg i.p.) also significantly antagonised the large increase in electroshock seizure threshold produced by ethanol (1.5 g/kg i.p.). In contrast, the hypothermia induced by ethanol (2 g/kg i.p.) was not altered by ORG 5878 (0.1 mg/kg i.p.). The effects of ORG 5878 showed an abnormal dose-response relationship, in that a high dose (1 mg/kg i.p.) did not significantly suppress any of the behavioural effects of ethanol examined although there was some indication that it attenuated the stimulant action of ethanol. ORG 5878 (0.1, 1 mg/kg i.p.) did not have any intrinsic effects on locomotion, seizure threshold or body temperature in mice. These results are the first demonstration that ORG 5878 may act as an ethanol antagonist in some paradigms. PMID- 1418113 TI - Atropine as an inhibitor of voluntary ethanol intake in male rats. AB - A single ethanol injection (2.0 g/kg, i.p.) administered to male rats will reduce voluntary ethanol intake (water vs. ethanol 10%) if tested for 24 hr, 6 days after the injection. Maximal inhibition, when compared to saline-injected controls (S), is seen after ethanol injections (E) once a week for 5-6 weeks. At this maximal inhibition atropine (A) or saline (S) was injected i.p. prior to the voluntary 24 hr intake of ethanol. In experiment 1, the doses 1 and 2 mg/kg were used, and in experiment 2, 4 and 8 mg/kg. Each experiment consisted of groups AE, SE, AS and SS, according to the above descriptions. In group AS, atropine reduced 24 hr voluntary ethanol intake with a maximal effect following the 4 mg/kg dose. In group AE, atropine did not increase the inhibitory effect induced by the ethanol injections. Total fluid intake was not influenced. After the treatment period a continuous choice (water vs. 10% ethanol) was offered for 8 (exp. 1) or 11 (exp. 2) weeks. During these evaluation periods the ethanol intake in group SE was always significantly smaller than the corresponding intake in group SS. In the atropine-injected groups (AE and AS) a similar significant difference in voluntary ethanol intake was observed at the beginning but not at the end of the evaluation periods. At the end of exp. 2 a significantly larger number of muscarinic binding sites was obtained in the cortex but not in the striatum of group SE when compared with groups AS and SS. In group AS a negative correlation was found in the striatum between the ethanol intake recorded after the atropine injection in week 5 and 6 and muscarinic binding sites. Atropine, probably by acting on muscarinic binding sites, seemed to have a specific inhibitory effect on voluntary 24 hr ethanol intake, which was similar to the effect induced by the ethanol injections. PMID- 1418114 TI - Alcohol elimination and the regulation of alcohol consumption in AA and ANA rats. AB - Previous studies have usually found that animals with either higher alcohol elimination rates or ADH (alcohol dehydrogenase, EC1.I.I.I) activities have higher voluntary intakes of alcohol than ones with lower elimination rates. This relationship has now been studied in the AA and ANA rat lines genetically developed, respectively, for high and low alcohol consumption. Female AA and ANA rats had their alcohol elimination rate measured before being given a free choice between 10% (v/v) alcohol and water for 3 weeks. The elimination rate was then measured again and liver ADH activity was determined. The alcohol elimination rate was significantly higher in AA than ANA rats before drinking and was increased by alcohol drinking in AA but not ANA rats. ADH activity was similar in both lines and unrelated to either alcohol drinking or elimination rates, suggesting that the enzyme activity is not a rate-limiting factor in the alcohol metabolism of these two lines. The present results support the conclusion that alcohol elimination and alcohol consumption are partially determined by genetics. Furthermore, although alcohol elimination itself probably does not have direct control over drinking, some factor related to the alcohol elimination rate appears to be among the mechanisms influencing the level of alcohol drinking. PMID- 1418115 TI - Measurement of carbohydrate-deficient transferrin by isoelectric focusing/western blotting and by micro anion-exchange chromatography/radioimmunoassay: comparison of diagnostic accuracy. AB - At present, the most reliable marker of recent and heavy alcohol intake is carbohydrate-deficient transferrin (CDT). While most CDT quantitation methods (including immunofixation and micro anion-exchange chromatography [MAEC] combined with radioimmunoassay [RIA]) either lack the precision required for diagnostic usage or are not commercially available, we recently described an isoelectric focusing/Western blotting (IEF/WB) procedure that provides sensitive and specific assessment of serum CDT content. However, a modified MAEC/RIA kit, supposedly more reliable than the original, is also being advanced as suitable for widespread clinical application. Therefore, we compared this modified MAEC/RIA procedure to the IEF/WB method of CDT quantitation in the following 108 subjects; 53 alcoholics undergoing detoxification without clinical or histological evidence of liver disease, 24 recently drinking alcoholics with biopsy-proven liver disease, eight alcoholics abstinent for more than 30 days with biopsy-proven liver disease, seven non-drinking patients with non-alcoholic liver disease, and 16 healthy controls. Although CDT measurements by the two methods were correlated (r = 0.60, P < 0.01), serum CDT values obtained with IEF/WB were nearly five-fold higher than those obtained with MAEC/RIA (e.g. 140.0 +/- 58 versus 28.5 +/- 16 mg/l among the active drinkers). Of the two methods, IEF/WB exhibited significantly greater sensitivity than MAEC/RIA for detecting recent, heavy drinking (75% versus 61%, P < 0.05) and generated no false positives whereas MAEC/RIA gave falsely elevated CDT levels in 37% of the abstinent alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418116 TI - Korsakoff minus Wernicke syndrome. AB - It is commonly believed that Korsakoff's amnesic state in alcoholics is characteristically the sequel to Wernicke's disease. However, in a study of 44 Korsakoff patients it was found that 33 had developed serious memory impairment without having had alarming neurological symptoms. This insidious nature of the onset of the disease indicates that all alcohol-dependent patients should be treated with vitamin B. PMID- 1418117 TI - Drinking patterns among medical in-patients with reference to MAST categories: a comparative study. AB - The aim of the study was to describe the drinking patterns and alcohol consumption of patients screened by the Michigan Alcoholism Screening Test (MAST) in a sample of medical patients from a general hospital of a French-speaking, wine-drinking country. Data were recorded using a structured interview administered to 103 consecutively admitted 20-75-year-old MAST-positive patients and 103 age-matched and sex-matched MAST-negative controls admitted to the same ward. Relevant differences between MAST-positive and MAST-negative patients included the frequent report of recent and total abstinence in MAST-positive patients (23% versus 4% in controls), their tendency to drink alone, and less often during mealtimes, at home, or with family or friends than MAST-negative patients. Alcohol consumption was significantly higher in MAST-positive patients of both sexes with 250 and 270 g per week being the optimal discriminative cut off level of consumption for men and women, respectively (kappa coefficient, 0.70 and 0.81, respectively). Regular drinking was the predominant drinking status of both MAST-positive and MAST-negative patients. This study suggests that a screening test such as the MAST, developed in an English-speaking country may be useful in a French-speaking, wine-drinking country. The test identified patients with drinking patterns that are culturally abnormal, yet in certain respects similar to those of alcoholic patients from other drinking cultures. These findings therefore emphasize the worldwide relevance of the concept of the alcohol dependence syndrome in addition to the transcultural usefulness of alcoholism screening tests. PMID- 1418118 TI - Functional imaging of blood brain barrier permeability by single photon emission computerised tomography and positron emission tomography. PMID- 1418119 TI - Economic aspects of neurosurgery. PMID- 1418120 TI - Current concepts of measurement of cerebrospinal fluid absorption and biomechanics of hydrocephalus. PMID- 1418121 TI - A multidisciplinary approach to the treatment of brain vascular malformations. PMID- 1418122 TI - Radiosurgery. PMID- 1418123 TI - Amniotic fluid index: correlation with amniotic fluid volume. AB - We calculated the amniotic fluid indexes (AFIs) of 310 women on 459 occasions. Normative data were analyzed and compared with data in several high-risk groups. In the normal gestations there was a progressive increase in AFI with advancing gestation until 32 weeks, after which there was a decline. The mean AFIs in abnormal gestations varied with the clinical diagnoses. These values were compared to those obtained by assessing amniotic fluid volume (AFV), that is a pocket more than 2 cm. There were 51 patients with abnormal AFVs. Forty-two had decreased fluid, six also had decreased AFIs; nine had increased AFVs and five (all with diabetes) also had increased AFIs. Thus, AFIs in normal pregnancies showed an orderly pattern of change with gestational age, and there was no accurate correlation between AFI and AFV. Thus, using AFV alone may lead to false interpretations of amniotic fluid status. PMID- 1418124 TI - Control of inspiratory timing in newborn infants. AB - In order to determine if inspiratory time in preterm infants was influenced by lung volume, two studies were carried out. In the first investigation, carbon dioxide was used to stimulate tidal volume to a level three to six times normal. The anticipated decrease in inspiratory time at increased tidal volumes was not found. These preterm infants behaved in a similar fashion to vagotomized animals studied in the same way by Clark and von Euler. In the second investigation, Hering-Breuer activity was measured in relation to lung volume changes occurring with growth, measured in a body plethysmograph. Although thoracic gas volume correlated well with age and weight, inspiratory slowing with airway occlusion was found to be independent of both age and lung volume. These investigations suggest that neurologic factors have a significant influence on the inspiratory time in newborn human infants. PMID- 1418125 TI - Comparison of fetal lung maturation in preterm singleton and twin pregnancies. AB - Preterm labor or premature rupture of membranes is one of the major complications of twin pregnancies and contributes to the increased maternal and perinatal morbidity and mortality. Forty-seven twin pregnancies and a comparable group of singleton pregnancies constitute the study population. These patients' pregnancies were complicated only by preterm labor. The lecithin to sphingomyelin ratio is used as an index of fetal lung maturation. Analysis of the data reveals that fetal lung maturation is biochemically comparable between twin and singleton pregnancies and among twins for a given gestational age in this clinical setting. PMID- 1418126 TI - Urinary arginine vasopressin excretion and hyponatremia in the sick neonates. AB - We attempted to clarify the renal physiologic response to arginine vasopressin (AVP) in the 12 sick neonates: three with respiratory distress syndrome (RDS), three with meconium aspiration syndrome, two with transient tachypnea of the newborn, two with neonatal asphyxia, and two low birthweight infants during the first 2 days of life. Plasma atrial natriuretic factor (ANF), urinary AVP, osmolality, free water clearance and creatinine clearance (Ccr) were measured at 8 to 16 hours of life (stage 1) and 24 to 32 hours of life (stage 2). Urinary AVP was expressed as the ratio of AVP to Ccr (urine AVP/Ccr). These subjects were divided into two groups: group A represented five infants with a urine AVP/Ccr ratio of 2000 or higher and group B, seven infants with a ratio of less than 2000 at stage 1. Hyponatremia occurred in two infants of group A at stage 2. Number of infants on mechanical ventilation was four in group A and one in group B. There were no significant differences in gestational age, birthweight, Apgar scores at 1 and 5 minutes, blood gas pH and mean arterial blood pressure between groups A and B. A good correlation was observed between logarithm of urine AVP/Ccr ratio and urinary osmolality (p < 0.01). A negative correlation was observed between logarithm of urine AVP/Ccr ratio and free water clearance (p < 0.01). Body weight of infants of group A at stage 2 was greater than at stage 1 (p < 0.05). Higher plasma ANF concentrations were observed in infants of group A at stage 2 when compared with those at stage 1 (p < 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418127 TI - Prenatal ultrasonic prediction of autopsy-proven pulmonary hypoplasia. AB - The sensitivity, specificity, and positive and negative predictive values for ultrasound estimation of fetal chest circumference in relation to autopsy-proven pulmonary hypoplasia are described in 58 singleton pregnancies at risk (39 with associated preterm premature rupture of the membranes at 30 weeks' gestation or less and of 12 or more days' duration, and 19 with associated anomalies). The ultrasonographic diagnosis of pulmonary hypoplasia was based on values at or below the lower limit of the 95% confidence intervals (for predicting a future observation) for normal pregnancies for each of the following tests; chest circumference in relation to gestational age and to femur length, for the chest circumference to abdominal circumference ratio and for a combination of the three measurements. At necropsy, the diagnosis of pulmonary hypoplasia was based on lung weight to birthweight ratio or radial alveolar counts. Pulmonary hypoplasia was diagnosed in 16 cases at autopsy. The clinicians and the pathologist were blinded to the ultrasonographic measurements. All tests performed well with a sensitivity of 0.55 to 0.80, specificity of 0.90 to 1.00, positive predictive value of 0.80 to 1.00, negative predictive value of 0.87 to 0.91, and an overall accuracy of 0.87 to 0.91. We conclude that ultrasound measurement of fetal chest circumference is of value with regard to the management of pregnancies at risk for lethal pulmonary hypoplasia. PMID- 1418128 TI - Perinatal bacteremia due to group F streptococci. AB - Perinatal septicemia due to Lancefield groups A, B, C, and G, but not the group F, streptococci have been documented. A case of perinatal bacteremia and septicemia due to group F streptococci is described. PMID- 1418129 TI - Significance of atypical cervical cytology in pregnancy. AB - To ascertain the significance of squamous atypia encountered during routine Papanicolaou smear screening in pregnancy, we reviewed our experience with 76 pregnant women seen during a 4-year period. All were evaluated with repeat cytology and colposcopy during pregnancy and again postpartum. Colposcopic examination during pregnancy revealed a normal transformation zone without evidence of intraepithelial neoplasia in 46 women. In six of these women, repeat cytology was interpreted as cervical intraepithelial neoplasia (CIN) grade 1. In 30 women, an abnormal transformation zone was identified--14 with a negative repeat cytology. In five women, the transformation zone was interpreted as compatible with CIN 2 or CIN 3. Colposcopically directed biopsies were performed in 31 women, in all but two postpartum. Of the 76 women, human papilloma virus or CIN was identified on biopsy in 16 women (21%). We propose that an isolated report of atypical squamous cells on cervical cytology obtained at the initial prenatal visit does not warrant colposcopic evaluation during pregnancy, unless a repeat cytology suggests CIN. Repeat cytology and evaluation to exclude infections and inflammatory lesions is appropriate. However, if a subsequent cytology is abnormal, postpartum colposcopy and colposcopically directed biopsies seem appropriate, since the prevalence of HPV or CIN was 21%. PMID- 1418130 TI - Transvaginal sonography at 5 to 14 weeks' gestation: fetal stomach, abnormal cord insertion, and yolk sac. AB - Transvaginal ultrasound evaluation of the fetal digestive system was performed on 1000 fetuses at 5 to 14 weeks' gestation. The normal physiologic process of the midgut herniation into the cord as well as the embryonal connection between the yolk sac and fetus were detected. Peristalsis of the stomach was noted as early as 14 weeks' gestation. Because gastric emptying is probably improper at this age, gastric pseudomasses were visualized in some cases. PMID- 1418131 TI - Prediction of pregnancy outcome by combined analysis of the fetal electrocardiogram and systolic time intervals. AB - A microcomputer-based system has been developed that continuously analyzes the fetal electrocardiogram (ECG) and Doppler cardiogram during labor by noninvasive means. Three systolic time intervals (preejection period [PEP], ventricular ejection time [VET], and isovolumetric contraction time), and four ECG parameters (P-R interval, QRS wave duration, T/QRS amplitude ratio, and S-T slope) are simultaneously measured and displayed. Normal values were derived from 126 uncomplicated pregnancies at term. A second group of 89 cases showing fetal heart rate patterns suggestive of fetal distress were subsequently studied: 64 had a good outcome (umbilical artery pH 7.20 or higher and a 5-minute Apgar score 7 or greater) and 25 were asphyxiated. Results were retrospectively analyzed. All asphyxiated fetuses had preejection period, PEP to VET ratio and T to QRS ratio values of more than 1 SD above the mean for the normal population. The PEP to VET ratio, which is an indicator of myocardial function independent of heart rate, proved to be the most sensitive predictor of fetal asphyxia. We conclude that analysis of systolic time intervals and ECG parameters of the fetal heart during labor improves the diagnostic accuracy of fetal heart rate monitoring. PMID- 1418132 TI - Fetoplacental and uteroplacental Doppler blood flow velocity analysis in premature rupture of membranes. AB - The value of Doppler velocimetry in predicting fetal distress or perinatal infection was investigated in 60 patients with premature rupture of the membranes (PROM) between 25 and 38 weeks of gestation. Studies were performed in the umbilical and uterine arteries after admission to the hospital and repeated every 24 to 76 hours until delivery. Results of the last study, performed less than 24 hours before delivery and comparison between longitudinal studies in the same patient, failed to disclose statistical differences between patients who did or did not develop the perinatal complications under study. We conclude that Doppler velocimetry is not a sensitive enough means of predicting fetal distress or infection in PROM. PMID- 1418133 TI - Severe preeclampsia in preterm pregnancy between 26 and 32 weeks' gestation. AB - Obstetric management of severe preeclampsia between 26 and 32 weeks' gestation presents a significant management dilemma. We examined the antenatal courses and perinatal outcomes of 67 such affected pregnancies and compared them with a group of 134 patients, matched for gestational age, who delivered after preterm rupture of membranes or preterm labor. Although the severe preeclamptic group had more patients with chronic hypertension and renal disease, 67% had no prior medical problems. The obstetric and other medical characteristics of both groups were similar. Neonatal outcomes in the severe preeclampsia group differed from those in the control group: they had lower mean birthweight, 5-minute Apgar score and umbilical arterial pH were lower, and their rates of respiratory distress syndrome and perinatal death were higher. Temporization for more than 72 hours was not possible in 60 of 67 preeclamptic pregnancies due to rapid deterioration of the mother (56 cases) or fetus (4 cases). The rate of poor neonatal outcomes in severe preeclampsia exceeded that expected with preterm delivery alone and may reflect preexisting fetal compromise, served better by early intervention and delivery. PMID- 1418134 TI - Ultrasonographic assessment of fetal and neonatal spleen. AB - To assess the growth and function of the fetal spleen, ultrasonographic examinations were performed on 229 normal fetuses, ranging from 20 to 41 weeks, menstrual age. Curvilinear relationships were found between the menstrual age and splenic length (R2 = 92.7%), circumference (R2 = 93.9%), and area (R2 = 95.2%). A normal range of splenic length, circumference, and area measurements for estimating the growth of the fetal spleen during normal pregnancy was generated. Splenic parameter values just after delivery were significantly lower than those measured within 7 days before delivery, and returned to former sizes 24 hours later, in both vaginal delivery and cesarean section groups. Splenic parameter values in the vaginal delivery group were also significantly lower than those in the cesarean section group, just after delivery. Moreover, neonatal splenic length showed negative correlations with lactate dehydrogenase (p < 0.001) and glutamic oxaloacetic transaminase (p < 0.05) in the umbilical venous blood, respectively. These results provide a foundation for the evaluation of fetal splenic growth and function during pregnancy and the early neonatal period. PMID- 1418135 TI - Significance of positive cervical cultures for Chlamydia trachomatis in patients with preterm premature rupture of membranes. AB - We tested the hypothesis that in patients with preterm premature rupture of membranes the presence of Chlamydia trachomatis in the cervix shortens the latent period (time from rupture of membranes to delivery) and increases the incidence of chorioamnionitis and early endometritis. A total of 178 conservatively managed patients with PROM between 22 and 35 weeks' gestation had cervical cultures for chlamydia, group B Streptococcus (GBS) and Neisseria gonorrhoeae performed at the time of rupture. Patients with GBS and gonorrhea were treated at the time the culture results were available and excluded from analysis. The remaining patients were divided into group 1: 26 patients (14.6%) positive for only chlamydia (and not treated until discharge from the hospital); group 2: 120 patients (67.4%) negative for all three organisms. The two groups did not differ in cesarean rate, duration of conservative management, hospital stay, or birthweight. Furthermore, the rates of chorioamnionitis (30.8% group 1; 38.3% group 2) or early endometritis (11.5% group 1; 20.8% group 2) were similar. We conclude that in patients with preterm premature rupture of membranes, the presence of chlamydia in the cervix appears to neither decrease the latent period nor increase the incidence of chorioamnionitis and early endometritis. PMID- 1418136 TI - An easy and accurate method of estimating newborn birthweight for resuscitation. AB - Emergency administration of medication based on birthweight is often required in newborn resuscitation. Actual weighing is often delayed because of the emergency situation. Therefore drugs are given according to weight estimates by physicians or nurses. The purposes of this study were to develop a measuring tape using the infant's length and head circumference to determine body weight and to evaluate the performance of the tape measurements to staffs' estimates. Weight, length, and head occipitofrontal circumference (OFC) measurements of 200 newborn infants were collected. By regression analyses, the best log curve for both length and OFC versus weight was determined. From these data, a measuring tape was constructed with the corresponding weights marked for both length and OFC. Forty five newborn infants with gestational ages of 26 to 40 weeks were studied. Prior to actual weighing, estimates of the birthweights were obtained and recorded from the tape measurements using both the length and OFC and staffs' estimates. For infants less than 2 kg, the average percent error was less by the tape length (1.2%) and OFC (0.7%) compared with staffs' estimates (-7.2%). The tape was also useful in estimating weights of small for gestational age infants. The tape OFC (7.8% error) was more accurate than staffs' estimates (26% error) in these growth retarded infants. The clinical precision of the tape was 3% with an intrameasurer variability of 5%. We conclude that estimating the birthweight in infants using our tape method is a practical and more accurate way than staff estimates, especially for low birthweight and small for gestational age infants. PMID- 1418137 TI - Characteristics associated with successful weaning in ventilator-dependent preterm infants. AB - Eighteen ventilator-dependent preterm infants with hyaline membrane disease were studied for 24 hours before and after an attempt at extubation. All were treated with theophylline prior to weaning and achieved average levels of 8.9 +/- 1.7 micrograms/ml (49 +/- 9 mumol/liter) in 13 successfully weaned infants and 8.4 +/ 1.1 micrograms/ml (47 +/- 6 mumol/liter) in 5 infants not extubated, p > 0.05. Infants successfully weaned were significantly (p < 0.01) older, more mature (29 +/- 1 versus 26 +/- 2 weeks' gestational age) and heavier (1107 +/- 236 versus 1016 +/- 256 gm) than infants not successfully extubated. Infants successfully weaned differed only in developing a greater maximal inspiratory force (33.8 +/- 12.3 versus 23.3 +/- 15.0 cm H2O) and higher compliance (1.1 +/- 0.3 versus 0.7 +/- 0.3) during the preweaning treatment period. These results indicate that maturity and size play a significant role in the ability to wean a preterm infant from the ventilator successfully, that maximal inspiratory force and compliance are higher in preterm infants who can be successfully extubated, and that methylxanthines do not uniformly improve pulmonary function in all potentially extubatable preterm infants. PMID- 1418138 TI - Preeclampsia effect on platelet count. AB - Thrombocytopenia is well recognized when preeclampsia is complicated by the hemolysis, elevated liver tests, low platelet count (HELLP) syndrome. We studied the effect of preeclampsia on the platelets of women whose platelet count and liver function were within normal range. We prospectively evaluated 67 preeclamptic women, gestational age 30 to 42 weeks, with disease of variable severity. The platelet counts of these patients, obtained within 24 hours preceding delivery, were significantly lower than the platelet counts of 71 control subjects. The platelet counts did not differ significantly between patients with mild and severe preeclampsia. Our findings suggest the existence of subclinical thrombocytopenia in preeclamptic women whose platelet values are within normal range. PMID- 1418139 TI - Reduction in the middle cerebral artery pulsatility index after decompression of polyhydramnios in twin gestation. AB - Amniotic fluid decompression was performed for symptomatic polyhydramnios complicating four sets of discordant twin gestations. Doppler ultrasound waveforms of the middle cerebral artery were determined before and after the procedure in seven of the eight fetuses. After amniocentesis, the pulsatility index of the middle cerebral artery (PIMCA) was reduced in all fetuses (p < 0.01). When one considers only the larger twin in each set, the magnitude of the change in PIMCA was relatively consistent among the different sets (-0.60 +/- 0.14; p < 0.01; range, -0.45 to -0.79). The smaller twins showed a much more variable response (-0.82 +/- 0.70; range, -0.05 to -1.75). The pulsatility index of the umbilical artery (PIUA) showed no consistent trend in the five subjects in which it was determined. In principle, the cerebrovascular dilation indicated by the PIMCA measurements may in part be due to acute increases in maternal and fetal carbon dioxide tensions following relief of maternal restrictive lung dysfunction. More importantly, the acute fall in amniotic fluid pressure--the external pressure to which the fetoplacental unit is exposed--leads to pooling of blood in fetal and placental veins, and thereby reduces the effective blood volume of the fetoplacental unit. This effective hypovolemia, functionally analogous to that produced by fetal hemorrhage, elicits changes in regional vascular resistances that favor cerebrovascular perfusion. The impact of acute amniotic fluid decompression on the fetal circulation reflected in the marked changes in PIMCA suggests a role for monitoring to avoid large acute changes in pressure during therapeutic amniocentesis. PMID- 1418140 TI - Ultrasonically measured biparietal diameter and abdominal circumference: intra- and interobserver variation in the third trimester. AB - Serial ultrasound measurements of the fetus under investigation is an important indicator of fetal growth, and thus fetal health. To assess how reliable those measurements are, a videotape was made, and, utilizing an ultrasound machine that allowed the placement of callipers on the videotape, the dispersion of the measurements obtained by 17 sonographers was noted. In the individual fetus in the third trimester of pregnancy, a 95% confidence interval of 3.5 and 2 weeks was found, respectively, for the measurements of the abdominal circumference and biparietal diameter (inter- and intraobserver variation combined). PMID- 1418141 TI - Evaluation of a fetal risk-scoring system. AB - A population of 2029 pregnant women (929 primiparas; 1100 multiparas) has been used to examine aspects of the calculation of obstetric risk scores from the presence of individual risk factors. The findings have been related to fetal outcome in these pregnancies and the following conclusions were reached: (1) the use of Bayes theorem for the calculation of a risk score is superior to the simple addition of weighted risk factors; (2) the diagnostic efficiency of a risk score is somewhat reduced when the data base used for calculation of the score is derived from a population different from that of the current pregnancy; (3) there is almost total overlap of risk scores in women with satisfactory and unsatisfactory fetal outcome. It is concluded that risk scores can be used to identify a small group of women at particularly high risk; in the remainder of the population scores are unhelpful except perhaps to indicate the women who do not require an intensive program of antenatal care. PMID- 1418142 TI - Maximum possible impact of tocolytics in preventing preterm birth: a retrospective assessment. AB - Although tocolytic drugs are widely used to try to stop preterm labor, their actual contribution to preventing preterm deliveries is unknown. Since tocolytic drugs are not used at the University of Manitoba, it was possible to estimate the proportion of preterm deliveries that might have been eligible for tocolytic drug therapy. Of 364 consecutive preterm deliveries between 24 and 35 weeks, only 9% would have been eligible for, let alone prevented by, tocolytic drug therapy, and even a smaller percentage of babies would actually have benefitted from their use. The use of tocolytic drugs can, at best, benefit only a very small percentage of babies born preterm. Whether the risks of treatment justify this small benefit is arguable. PMID- 1418143 TI - Prenatal presentation of congenital chloride diarrhea: clinical report and review of the literature. AB - A case of congenital chloride diarrhea was diagnosed after delivery in a patient whose antenatal course was notable for massively dilated small and large bowel and persistent, severe hydramnios refractory to therapy. The pathophysiologic mechanism is a dysfunctional chloride-bicarbonate exchange in the brush border of the ileum. Antenatal presentation, prenatal diagnosis, and a review of the current literature are discussed. PMID- 1418144 TI - Creation of a neonatology facility in a developing country: experience from a 5 year project in China. AB - In 1983, Project HOPE was invited by Zhejiang Medical University to collaborate in developing a neonatal intensive care unit (NICU) at the Children's Hospital in Hangzhou, China. The initial approach involved renovating facilities, purchasing equipment and supplies, placing short-term consultants in the unit as teachers, and bringing selected leaders to the United States for brief fellowships. An evaluation at 18 months disclosed poor organization and leadership, inconsistent clinical care, and unsatisfactory utilization and maintenance of facilities and equipment. Therefore the strategy was revised to include long-term physician and nursing consultants, establishment of ties with HOPE Biomedical Engineering projects, and development of formal education programs. The unit was transferred to the Chinese after 4 years and an evaluation 1 year after transfer revealed an actively functioning independent NICU with evolving effective leadership, established purchasing and preventive maintenance programs, and continuing formal education activities. Unsatisfactory progress was found with the development of a transport system, some laboratory capabilities, adherence to admission and discharge policies, and various other administrative issues. Although the goal of establishing an independent NICU was realized, perhaps the most lasting accomplishment was the establishment of a facility and a format for development of a transportable education program aimed at improving neonatal care practices throughout a larger region of China. PMID- 1418145 TI - Neonatal thrombosis with anticardiolipin antibody in baby and mother. AB - The anticardiolipin antibody is associated with increased risk of thrombosis, which is manifested with various clinical presentations, including vascular thrombosis, recurrent fetal wastage, and neurologic defects. We report a case of neonatal thrombosis occurring in the renal vein and inferior vena cava associated with moderate positive anticardiolipin antibody titer in the baby while the maternal serum showed even stronger anticardiolipin antibody of immunoglobulin G class. Subsequent follow-up over the 4 months postpartum period showed a disappearance of the antibody in the baby, whereas the mother's antibody persisted. This case illustrates the fact that the maternal anticardiolipin antibody can be transferred to the fetus and may be a risk factor for thrombosis in the neonates. Anticardiolipin antibody syndrome should be considered in the differential diagnosis of neonatal thrombosis. PMID- 1418146 TI - Surface tension of therapeutic surfactants (exosurf neonatal, infasurf, and survanta) as evaluated by standard methods and criteria. AB - Three commercial preparations for the treatment of neonatal respiratory distress syndrome (NRDS), Exosurf Neonatal (EX), Infasurf (IN), and Survanta (SU), were studied at 37 degrees C in both a pulsating bubble surfactometer and a vertical film surface balance. "Static" characteristics of adsorbed films were assessed with "bubble" at maximum radius (Rmax) and at minimum radius (Rmin). Adsorption time was time to stable film formation (gamma equilibrium). In dynamic experiments, the bubble was cycled (compressed-decompressed) between Rmax and Rmin at 20, 40, and 80 cpm. Spread films were cycled in the surface balance between maximum area (Amax) and minimum area (A(min)) at 1.5 cpm. In all experiments, maximum surface tension (gamma max) coincided with Rmax or Amax and gamma min with Rmin or A(min). All trials were continued until gamma max and gamma min were reproducible. Data were evaluated according to standard criteria for normal function both in vivo and in vitro of lipid mixtures (EX) or natural surfactants (IN, SU) prepared for treatment of NRDS. All preparations failed two of the four criteria, adsorption in the time of a deep breath and maintenance of stable, low gamma. Adsorption required 10 to 20 seconds and stable gamma was achieved only at equilibrium gamma, > 17 mN/m. IN and SU conformed in general to two criteria, gamma approaching zero on compression and low surface compressibility (< 0.09 m/mN), whereas spontaneously formed films of EX did not. EX was idiosyncratic in that these two criteria were met only after an apparent change of film conformation had been effected, possibly related to elimination of preparation additives from the surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418147 TI - Prenatal determination of demographic and attitudinal factors regarding feeding practice in an indigent population. AB - Demographic and attitudinal factors influencing the decision to breast- or bottle feed were evaluated early in pregnancy by survey of 307 women in a low-risk prenatal obstetric clinic at a publicly funded hospital in Houston, Texas. Subjects responded to 17 demographic and 24 attitudinal questions. Racial classification revealed blacks 36.4%, whites 29.2%, and hispanics 30.8%. Twenty five percent of the completed surveys were in Spanish. Of the total sample, 26.7% planned to breast-feed, 48.2% planned to bottle-feed, and 25.1% planned to do both. Multiple logistic regression analysis revealed six prominent independent risk factors for bottle-feeding. The most significant variable was lack of support for breast-feeding from a significant other (husband, mother, other relative, or friend), which had a odds ratio (OR) of 456.3. Other attitudinal variables achieving independent significance were disagreement with the statements "breastfeeding protects against disease" (OR = 4.0), "breasts were made for breastfeeding" (OR = 8.0), and "I want to know more about breastfeeding" (OR = 120.0). Significant demographic variables identified were completion of less than 12th grade (OR = 32.1), and age less than 35 years (OR = 43.3). These findings indicate the influence of significant others in the decision to breast feed and suggest that future educational programs should require their inclusion if the prevalence of breast-feeding in this population is to be increased. PMID- 1418148 TI - Group B streptococcal colonization in the diabetic gravida patient. AB - Previous reports have suggested that pregnant diabetic patients have higher carriage rates of group B Streptococcus (GBS) than nondiabetic gravidas. In order to evaluate this in our population, we cultured the posterior pharynx, endocervix, vagina, and rectum of 101 diabetic pregnant women and 100 nondiabetic gravida patients. The colonization rate of GBS was higher in the diabetic population, 31.7%, than in the nondiabetic group 19.0%, (p < 0.039). The vagina was the site most often positive in both diabetic and nondiabetic populations (23.8% and 17.0%, respectively, p = NS). The second site to culture positive overall and the only individual site that was positive significantly more often in diabetics was the rectum (16.9% versus 7.0%, p < 0.05). Differences in colonization rates were not evident when insulin requirement and diabetic classes were considered. PMID- 1418150 TI - Developmental aspects of percutaneous caffeine absorption in premature infants. AB - Caffeine is commonly used in the treatment of apnea of prematurity. The skin of preterm infants varies considerably in its level of maturity. To understand skin absorption in low birthweight infants (less than 1500 gm) with gestational age between 26 and 34 weeks, a group of 56 preterm babies was studied after percutaneous application of 7.5 mg twice daily of caffeine for babies with birthweight less than 1000 gm and 10 mg twice daily for babies with birthweight more than 1000 gm. The reported technique is a useful alternative method of drug administration in premature babies. This study indicates an inverse relationship between gestational age and skin absorption contributing to a better understanding of skin barrier function in the newborn. PMID- 1418149 TI - Hypothalamic-pituitary-adrenal axis function in premature neonates after extensive prenatal treatment with betamethasone: a case history. AB - Tests of hypothalamic-pituitary-adrenal axis function were performed on a set of 32-weeks' gestation triplets whose mother received 16 injections of betamethasone over 8 weeks prior to delivery to induce fetal lung maturation. The purpose of these studies was to determine if clinically significant suppression of fetal adrenocortical function occurred as a result of this repeated and prolonged prenatal exposure to glucocorticoids. Serum cortisol levels were measured on cord blood from each patient. Morning serum cortisol and 11-deoxycortisol levels were measured before and after an oral dose of metyrapone given at midnight on day 5. All three infants were clinically well at birth and had no evidence of hyaline membrane disease. Cord blood cortisol levels were low in each infant (1.97 +/- 0.25 micrograms/dl). By day 5, morning cortisol levels had become normal for each infant (10.77 +/- 2.42 micrograms/dl). Following the metyrapone dose, the 11 deoxycortisol levels rose 10- to 20-fold for each infant, indicating normal function of the hypothalamic-pituitary-adrenal axis by day 6. Adrenocortical suppression following multiple courses of prenatal betamethasone appears to be similar in degree and duration to that reported following brief antenatal therapy with this medication. Further studies are needed to confirm these anecdotal observations. PMID- 1418151 TI - Hemodynamic effects of combining epinephrine with nitroglycerin or nitroprusside during group B streptococcal sepsis in piglets. AB - Septic shock in young children is often characterized by clinical findings consistent with a reduction in cardiac index (CI) and elevation of systemic vascular resistance index (SVRI). In this context, infusion of inotropic agents, alone or in combination with vasodilators, has been recommended. We have utilized group B streptococcal (GBS) infusion in piglets to develop a model of low-CI/high SVRI septic shock, and report here the effects of the combination of epinephrine (EPI) plus either nitroglycerin (NG) or nitroprusside (NP) in this model of infant sepsis. Piglets were anesthetized, intubated, and ventilated. All piglets received GBS continuously for 90 minutes and were further divided into three experimental groups. Group 1 received NG 16 micrograms/kg.min plus EPI 2 micrograms/kg.min; group 2 received NP 10 micrograms/kg.min plus EPI 2 micrograms/kg.min, and group 3 received 0.9% sodium chloride (saline) only. CI, which fell for all three groups at the onset of GBS infusion, rose significantly in group 2 animals (but not in groups 1 and 3). This effect was mediated entirely by an increase in myocardial stroke volume. Aortic blood pressure, initially unaffected by GBS infusion, rose significantly in both group 1 and 2 compared with group 3. SVRI, which rose for all three groups at the onset of GBS infusion, was further markedly elevated in group 1 (but not in groups 2 and 3). Pulmonary artery pressure and pulmonary vascular resistance index, both significantly increased after GBS infusion, were reduced in group 2 but not groups 1 and 3. These observations illustrate the potential for unexpected, and possibly detrimental, hemodynamic consequences when vasoactive agents are combined in young septic animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418152 TI - Prophylactic and emergent arterial catheterization for selective embolization in obstetric hemorrhage. AB - Treatment of obstetric hemorrhage by the selective embolization of damaged pelvic vessels under fluoroscopy holds promise as an alternative to surgical intervention. Unfortunately, the effectiveness of selective embolization is often compromised by its use in emergent settings following the failure of primary operative approaches. Therefore we compared the efficacy of prophylactic versus emergent catheter placement for selective embolization in nine patients with or at risk for obstetric hemorrhage. In four patients with acute obstetric hemorrhage catheterization and embolization was carried out following the failure of initial medical and surgical approaches. In five patients determined to be at risk for intrapartum hemorrhage based on sonographic findings, catheters were inserted into the hypogastric vessels prior to elective cesarean delivery. Three of these five patients subsequently required selective embolization. In comparison to patients undergoing selective embolization following prophylactic catheter placement, patients in the emergent group all had a coagulopathy at the time of embolization, sustained substantially greater blood loss, and had an increased rate of postpartum complications. Finally, there was a significant reduction in total embolization time and therefore in radiation exposure in patients undergoing prophylactic catheter placement prior to selective embolization. These data support the conclusion that in patients determined to be at risk for intrapartum or postpartum hemorrhage the prophylactic placement of catheters allows for selective embolization in a hemodynamically intact patient with stable coagulation indices, theoretically reducing the risk of maternal morbidity and possibly mortality. PMID- 1418153 TI - Ultrasound diagnosis of immature cervical teratoma: a case report. AB - We report a case of cervical teratoma in a term female infant born to a 20-year old white woman. There are rare tumors in neonates, occurring in approximately 1 in 20,000 to 1 in 40,000 live births. These tumors are accurately defined by ultrasound. Although benign, cervical teratomas cause respiratory compromise. In this case the tumor was removed surgically with no recurrence at the 10-month follow-up. PMID- 1418154 TI - Neonatal alloimmune thrombocytopenia after maternal immunization with paternal mononuclear cells: successful treatment with intravenous gamma globulin. AB - We report a case of neonatal alloimmune thrombocytopenia and intracranial hemorrhage in an infant whose mother received immunizations of paternal mononuclear cells. This therapy is designed to prevent unexplained first trimester miscarriages. No previous cases of platelet autoimmunization associated with maternal immunization with paternal mononuclear cells has been reported. Treatment with antenatal maternal infusions of intravenous gamma globulin (IVGG) did not prevent fetal thrombocytopenia, but IVGG may become the treatment of choice for postnatal, antibody-mediated thrombocytopenia of the newborn. PMID- 1418155 TI - Detection of intra-amniotic infection by gas-liquid chromatography. AB - The use of gas-liquid chromatography to detect short-chain organic acids in the amniotic fluid of patients with amnionitis has been previously described. Most of the studies describe patients in the early third trimester with such infections. The purpose of the current study was to confirm the correlation of infection with increased production of organic acids and to assess the effect of gestational age on the presence of these short-chain fatty acids in the amniotic fluid. Six patients with confirmed chorioamnionitis were used as positive control subjects. Seventy-two patients at various gestational ages from 18 to 42 weeks with negative Gram's stain and culture results from the amniotic fluid were used as negative control subjects. The data revealed an increased production of organic acids, particularly pyruvic, oxalic and succinic, in patients with amnionitis regardless of gestational age. Interestingly, patients with noninfected amniotic fluid also revealed an increase in the concentrations of volatile organic acids between 27 and 32 weeks' gestation. It appears from this study that previous results correlating chorioamnionitis with an increased production of organic acids in the amniotic fluid may have been confounded by gestational age. PMID- 1418156 TI - Creatine kinase and creatine kinase isoenzymes as a marker of uterine activity. AB - Creatine kinase (CK) and CK isoenzymes are known to fluctuate in labor. Reliable information about the longitudinal changes of CK and CK isoenzymes during labor is sparse. Nevertheless, they have been used to direct care in women with cardiopulmonary disease and preterm labor requiring tocolysis. This study evaluated fluctuations of CK and its isoenzymes longitudinally across labor in 49 women. Blood samples were obtained at 33 to 34 weeks' estimated gestational age, on admission in labor at 3 cm or less dilation, 8 cm to complete dilation, and postpartum in the recovery room. Specimens were analyzed for total CK, CK-MM, CK MB, and CK-BB activity. CK levels increased for all peripartum patients (p < 0.001). CK activity at 3 cm was greater than at 34 weeks (p < 0.01). Furthermore, the early rise in CK activity was greater in those in active labor compared with those who required oxytocin stimulation (p < 0.001). CK values at 8 cm and postdelivery (mean IU/liter) were often above nonpregnant norms. The early rise of CK in spontaneously laboring patients versus those requiring oxytocin augmentation may represent a difference in uterine activity. Nonpregnant normative data for CK is not appropriate when assessing cardiovascular side effects of betamimetic therapy. PMID- 1418157 TI - Is there a "dominant twin" in utero? AB - A prospective study of 98 pairs of nonstress tests (NSTs) was obtained simultaneously from members of 30 twin gestations. Fifty-five percent of the total fetal heart rate (FHR) accelerations of both twins were associated with each other and occurred within 15 seconds of each other. There were 8.46% synchronous FHR accelerations of both twins, possibly reflecting evoked fetal movements. Statistical analysis failed to reveal evidence of a dominant twin in utero, with one twin initiating the majority of coinciding fetal movements with statistical significance in only three gestations. Examination of combinations of the 30 separate individual significance tests using techniques of meta-analysis demonstrated a p value of 0.81, indicating lack of dominance in any of the 30 pairs of twins. The probability plot, consistent with the large p value for the combination test statistic, suggested that fetal movements in two gestations are related, strengthening the hypothesis of in utero tactile communication between twins. We conclude that the existence of a "dominant twin" in utero cannot be detected by electronic FHR monitoring methods. PMID- 1418158 TI - Hemodynamics associated with the diagnosis and treatment of pheochromocytoma in pregnancy. AB - A pregnant woman with an undiagnosed pheochromocytoma is described. Her presentation at 29 weeks' gestation was consistent with preeclampsia. Noninvasive measurement of cardiac output and ambulatory monitoring of blood pressure provided data that facilitated making the appropriate diagnosis and managing the patient until delivery at term. PMID- 1418159 TI - Sonographic fetal growth curves from an indigent population in Atlanta, Georgia: I. Singleton pregnancies. AB - The sonographic estimation of gestational age relies on standards of normal fetal growth established in highly selective patient populations. The majority have used middle-class, Caucasian gravidas with excellent menstrual dating criteria. These reference populations differ considerably from the indigent patient population in most southern medical centers: menstrual dating is often imprecise and there is a high rate of low birthweight infants delivered. Therefore, we established models of fetal growth in a southern, indigent, predominantly black patient population. We also compare our study to other sonographic studies. PMID- 1418160 TI - Effect of magnesium sulfate on the vascular actions of norepinephrine and angiotensin II. AB - Magnesium sulfate is used for seizure prophylaxis in patients with preeclampsia. It also has significant effects on calcium metabolism and could, therefore, alter the pressor response to calcium-dependent vasoconstrictors. The present in vivo rat study examined the effect of magnesium sulfate to alter the pressor response to norepinephrine (NE) and angiotensin II (A II). Magnesium doses were chosen to approximate those used in treating preeclampsia. NE resulted in a significant rise in mean arterial pressure (delta MAP, 46 +/- 3.7 mmHg; p < 0.001). A II also resulted in a significant rise in MAP (delta MAP, 23 +/- 3.6 mmHg, p < 0.02). Magnesium sulfate alone had no significant effect on MAP but attenuated the pressor response to both NE (delta MAP, 16 +/- 1.5 mmHg) and A II (delta MAP, 12 +/- 2.5 mmHg). After discontinuation of the magnesium sulfate infusion, the control pressor responses to NE and A II were again seen (delta MAP, 39 +/- 3.5 mmHg and delta MAP, 28 +/- 4.2 mmHg, respectively). Although magnesium sulfate is not a primary antihypertensive agent, it may have effects on blood pressure by attenuating the actions of circulating vasoconstrictors. PMID- 1418161 TI - Surgical treatment of incompetent cervix. AB - A comparison of multiple factors in the surgical management of cervical incompetence was carried out in 114 procedures. Factors examined included training level of the operator, gestational age, cervical effacement and dilation at the time of operation, diagnostic evaluation, Shirodkar or McDonald procedure, year of the procedure, and tocolytic therapy. The endpoint for successful outcome was defined as 37 weeks or newborn weighing over 2500 gm rather than neonatal survival, thus differing from previous studies. All patients were delivered vaginally unless there was an obstetric indication for cesarean delivery. The most important determinants of a term birth in patients with incompetent cervix were operator experience and the use of a Shirodkar procedure. PMID- 1418162 TI - Outcome of pregnancy in class A1 and A2 gestational diabetic patients delivered beyond 40 weeks' gestation. AB - The charts of all diabetic women and their infants delivered during the years 1983-1988 in our department were reviewed. The test group included consecutive gestational diabetic women class A1 (n = 65) and class A2 (n = 59), who delivered beyond 40 weeks of gestation. The mean gestational age at delivery was 40.90 weeks (range, 40.0 to 42.57) in class A1 and 40.49 weeks (range, 40.0 to 42.28) in class A2 patients. The first control group matched for age, parity, and presentation included 65 gestational diabetic patients class A1 and 59 A2 who delivered prior to 40 weeks' gestation. The second control group matched for age, parity, and presentation included 124 nondiabetic patients who delivered beyond 40 weeks of gestation (mean, 41.04 +/- 0.83 weeks). By allowing the pregnancies of gestational diabetic patients class A1 and class A2 to proceed beyond 40 weeks of gestation, we did not increase the incidence of perinatal mortality and morbidity rate. The cesarean section rate was low (10.76% in class A1 and 22.03% in class A2). We suggest that not only elective intervention prior to 40 weeks of gestation is to be avoided, but an attempt should be made to allow the gestational diabetics class A1 and class A2 to proceed to spontaneous labor. PMID- 1418163 TI - Effects of physical activity and life-style factors on uterine contraction frequency. AB - In this cohort study, uterine contractions were recorded in 81 low-risk pregnant women who wore ambulatory tocodynamometers continuously during three 72-hour periods at advancing gestational ages. During these periods, they also recorded their daily activities in a diary. Examination of the data, in general, revealed no association between uterine contraction frequency and habits such as smoking, alcohol consumption, or drinking caffeinated beverages. Physical activities, such as prolonged standing, heavy housework, lifting, or organized exercise also did not appear to affect uterine contraction rates. Only climbing stairs and walking were associated with increased contraction frequencies, but this effect, although statistically significant, was relatively small in magnitude and was present only during the last gestational age period monitored (30 to 33 weeks). PMID- 1418164 TI - Vaginal ultrasound: an invaluable component of modern obstetric ultrasound. PMID- 1418165 TI - Applicability of tocolytic therapy. PMID- 1418166 TI - [Control of breathing during exercise]. AB - Although the control of breathing during exercise has been studied extensively that both neural and humoral factors may play a role in mediating the exercise hyperpnea, it remains unresolved whether the response is due solely to neural or humoral mechanisms and how the pulmonary gas exchange matches to the tissue exchange rates. At just onset of exercise ventilation can increase abruptly within 1 to 2 breathes (Phase I). Such a rapid increment of ventilation is not attributed to the humoral factor(s) due to the circulation delay from muscle metabolites. More rapid mechanism(s) such as irradiation from brain stream, afferent neurogenic control, blood flow increment as cardiodynamic theory might be considered. During moderate exercise intensity with a step function, ventilation increased exponentially to the steady state (phase II) after an abrupt increase at just onset of exercise. In this phase II, the breathing is controlled as to exchange the oxygen and carbon dioxide at rates appropriate for the acid-base homeostasis regulation. As a result, arterial blood gases and acid base status must maintain within a narrow range despite of extremely enlarged metabolic rates by exercise. Some humoral factor(s) might be mediated for the control of breathing such as mean steady state error theory, arterial blood gases oscillation theory, feedback system by CO2, or optimization theory. At the heavy exercise intensity, anaerobic metabolism was supplemented to product for the enhanced energy requirement, so that ventilation increased non-linearly with oxygen uptake due to the lactoacidosis and its buffering activity. There has been a debate concerning cause and effect relationship between blood lactate increment and hyperpnea during exercise. Recently, arterial potassium concentration resulted from depolarization due to muscle contraction during exercise might stimulate to carotid bodies for increasing ventilation. PMID- 1418167 TI - [Subcutaneous fat distribution in Japanese women. Part 1. Fat thickness of the trunk]. AB - The thickness of subcutaneous fat were measured at 215 different points on the trunk in Japanese young women with using B-mode ultrasonic device. Subjects were 10 healthy Japanese females aged from 20 to 24 years. Average subcutaneous fat thickness over the trunk of 10 subjects was 9.8 mm, and it's standard deviation was 1.5 mm. Subcutaneous fat thickness showed the higher value at the buttock, the breasts and the abdomen and the lower value at the back. The difference of fat distribution between obese subjects and lean subjects was exhibited mainly on the abdominal parts but not on the chest and back parts of the trunk. PMID- 1418168 TI - [Warming-up under cold environment]. AB - Warming up procedures in the many antecedent reports, are almost under normal ambient temperature and they do not treat the warming up under low temperature. The purpose of this study was to investigate the effects of warming up by intensity and time in submaximal treadmill exercise (90% VO2max intensity during 10 minutes) on physiological parameters under cold environment in climate chamber (room temperature: 10 degrees C, relative humidity: 70%, wind velocity: under 0.2 m/sec). Eight trained collegiate basic skiers performed main exercise for 5 minutes after the following warming up conditions: NoW-up (no warming up), W50-15 (50% VO2max intensity 15 minutes), W70-15(70% VO2max intensity 15 minutes), W50 30(50% VO2max intensity 30 minutes) or W70-30(70% VO2max intensity 30 minutes). It was concluded that the most effective intensity and time of warming up in these conditions were 50% VO2max intensity and 30 minutes duration, that is, rather low intensity and longer duration time. It was suggested that a warming up with a high intensity and short duration was effectless under cold. PMID- 1418169 TI - Optimum comfort limits determination through the characteristics of asymmetric thermal radiation in a heated floor space, "ondol". AB - This study was undertaken to evaluate the effects of the asymmetric radiation on thermal comfort, and to suggest the optimum comfort limits in a radiant heating space. The index of V.R.T. (Vector Radiant Temperature) was used to describe the environmental quality of the heated floor space. Optimum comfort limits of this space were suggested through both theoretical and empirical studies. It is recommended to use not only man's sensation of the ambient air but also that of the floor surface for the determination of the optimum comfort limits on the heated floor space such as an "Ondol" in Korea. In the present study the optimum comfort limits were suggested in terms of the V.R.T. The optimum limits obtained were as follows: the vector radiant temperature 11.0 approximately 15.0 K. PMID- 1418170 TI - Influence of noise on heart rate and quantity of work in mental work. AB - In the present study, we investigated the correlation between the physiological function, heart rate (HR) and the quantity of work performed when A-weighted sound pressure level of factory noise or construction noise was varied during the mental operations of calculation and erosion. Furthermore, we looked for differences in the effects of sound noise and music on the quantity of work performed. The A-weighted sound pressure level was set at four levels of background noise, i.e. 60, 70 and 80 dB (A). The music sound level was set at 70 dB (A). The subjects were exposed to factory noise, construction noise and music during their mental work. A balanced factorial experiment was conducted with a total of 16 combinations of types of mental work (two levels of calculation and erosion), sound noise (two levels of factory and construction sound noise), and A weighted sound pressure levels (four levels). The order of the experimental procedures was determined at random. The following conclusions were made from the findings of the study. 1) HR elevation occurred due to exposure to sound noise, and further increase in HR resulted from an increase in the A-weighted sound pressure level. This result can be attributed to the action of sound noise as a stressor, which excites sympathetic nerves, leading to an elevation of HR. 2) The quantity of work performed decreased with an increase in the A-weighted sound pressure level. 3) When the subjects were exposed to music with an A-weighted sound pressure level of 70 dB (A) instead of sound noise of the same level, almost no elevation of HR was observed. However, the quantity of work completed when exposed to music was less than that performed when exposed to sound noise of the same A-weighted sound pressure level. PMID- 1418171 TI - The effect of color temperature of lighting sources on the autonomic nervous functions. AB - The present study was designed to investigate the effects of color temperature of lighting sources on the heart rate variability. Eight male students volunteered as subjects. The heart rate variability during task and rest sessions were estimated under nine different lighting environments consisting of three levels of color temperature (3000 degrees K, 5000 degrees K and 6700 degrees K) and three levels of illuminance (1001x, 3001x and 9001x). The lighting condition caused no effect on the mean heart rate. On the other hand, the power spectrum of heart rate was significantly influenced by the lighting conditions. The respiratory sinus arrhythmia component and Mayer wave related sinus arrhythmia component of the power spectrum increased under higher color temperature conditions. Judging from the consistency of heart rate level, the balance between the effects of parasympathetic and sympathetic nervous systems remained at a constant level irrespective of lighting quality and intensity. Therefore, both parasympathetic and sympathetic nervous functions were concluded to be enhanced under higher color temperature conditions. The light with higher color temperature was considered to activate the autonomic nervous function more than the light of lower color temperature. The effect of color temperature was much remarkable in the rest session comparing with the task session. This fact was discussed from the viewpoint of color temperature effect in environmental lighting. PMID- 1418172 TI - [Estimation of energy expenditure and the validity of pitch counting during walking and jogging by piezoelectric materials]. AB - The purpose of the present study was to assess the validity of Piezo-electric accelerometer for estimating energy expenditure in walking and jogging. Energy consumption by oxygen uptake was determined during steady state level of treadmill walking at the speed of 60, 80 and 100 m/min and jogging at the speed of 100, 120, 140, and 160 m/min for 10 subjects. There was a highly significant correlation between the energy consumption and the estimated energy expenditure by an accelerometer despite the attached position (r = 0.912 at the waist, r = 0.915 at the chest, P < 0.001), which suggests accurate estimating energy expenditure in the field. PMID- 1418173 TI - [Physical fitness and its relationship with life style for persons of middle or advanced age]. PMID- 1418174 TI - Antineoplastic effects of gallium nitrate on human medulloblastoma in vivo. AB - Gallium nitrate possesses antineoplastic activity against certain solid tumors and has been demonstrated to be an effective agent in reducing cell proliferation and DNA synthesis in the medulloblastoma Daoy cell line in vitro. In prior studies, gallium inhibited the cellular uptake of 59Fe by brain tumor cells; however, this block in 59Fe uptake was variable and closely paralleled the inhibitory effects of gallium on cell growth. In vivo trials now have been conducted and have yielded some promising results. Nude mice received intradermal injections of medulloblastoma Daoy and then allowed to grow tumors. When the mice had developed at least one tumor between 9 to 10 mm in diameter, a 10-day course of intraperitoneal gallium nitrate injections was initiated. Gallium nitrate treatment reduced overall tumor growth rate and reduced actual tumor size. Nephrotoxicity was severe, but may be preventable by continuous gallium infusion and use of diuretics and hyperhydration. PMID- 1418175 TI - Neurologic outcome of propionic acidemia. AB - Twenty patients with propionic acidemia were reviewed retrospectively. Two groups were identified: those who presented in the first week of life (11 patients) or after the neonatal period (9 patients). The early onset of disease had a much higher death rate (hazard ratio: 7.52) and all patients in this group were mentally retarded (IQ < or = 60). Movement disorder was common in both groups. Of the early-onset group, 3 patients had mild chorea or dystonia. Four in the late onset group had a severe movement disorder. In the late onset group, cranial computed tomography disclosed transient basal ganglia lucencies following an episode of metabolic decompensation; however, no disturbance in amine neurotransmitter metabolite concentrations were found in the cerebrospinal fluid. PMID- 1418176 TI - Vigabatrin in intractable childhood epilepsy: a retrospective study. AB - The effects of vigabatrin were studied over a 6-month period in 43 patients with intractable epilepsy. Children with complex partial seizures, with or without secondary generalization, responded best with more than one-half achieving a greater than 50% reduction; generalized tonic-clonic seizures also improved but there was no significant change in absence or myoclonic seizures. Four patients are seizure-free on monotherapy with vigabatrin. The drug was well tolerated with few side effects. PMID- 1418177 TI - Immunodiagnosis of bacterial enteric infections: where do we stand? PMID- 1418178 TI - The change of allergen-specific IgG subclass antibodies during immunotherapy in mite-sensitive asthmatic children. AB - Fifty-six Dermatophagoid farinae (D.f)-sensitive asthmatic children were hyposensitized by D.f-crude extract for two years. Serum total IgG subclass antibodies and D.f-specific IgE and IgG subclass antibodies were measured by ELISA before and after 2 years of treatment. The results showed that 1) After two years of treatment, there were significantly higher levels of total serum IgG1 in both responder and non-responder groups than those before treatment (p less than 0.01). The responder group also had significantly higher values of total IgG2 and IgG4 after immunotherapy (IT) (p less than 0.05), but not in the non-responder group. 2) The serum levels of D.f-specific IgG3 and IgG4 antibodies in responder group increased significantly after IT (p less than 0.05). On the contrary, the D.f-specific IgE and IgG1 IgG1 in the responder group were significantly lower than those before IT. No signi- in the responder group were significantly lower than those before IT. No signi-body titres before and after IT was found in non responder group. 3) There was a significant correlation between the total IgG4 and D.f-specific IgG4 antibody (r = 0.634, p less than 0.01). The correlation coefficient was 0.634. No correlation was found between the other IgG subclass antibodies and D.f-specific IgG subclass antibodies. 4) Correlations between the levels of D.f-specific IgE and IgG subclass antibodies were highly significant both in IT-responder and non-responder groups. There was a significant correlation between the levels of D.f-specific IgG1 and IgG4 in non-responders, while no relationship was observed in the responder group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418179 TI - Antinuclear antibody detection using streptavidin-biotin-peroxidase complex on HEp-2 cell substrate. AB - The streptavidin-biotin-peroxidase complex (SABC) technique was compared to conventional indirect immunofluorescence (IIF) for the detection of anti-nuclear antibody (ANA) on HEp-2 cell substrate. SABC showed higher specificity and predictive value and gave more reproducible titres and clearer staining patterns than IIF in sera from a series of rheumatic disease patients. Sera from 80 patients with various types of rheumatic diseases and 20 without rheumatic disease were further tested using the SABC method. All systemic lupus erythematosus (SLE) sera were positive. The overall sensitivity was 95%, specificity 90% and predictive value 97% for rheumatic disease. The rim pattern was associated with SLE and mixed connective tissue disease. The nucleolar/homogeneous pattern was associated with scleroderma and SLE in remission. ANA titre and staining pattern have limited value in the clinical assessment of rheumatic disease; however, ANA has very high sensitivity for SLE and remains an excellent screening test. PMID- 1418180 TI - The presence of specific IgE to salicyloyl and O-methylsalicyloyl in aspirin sensitive patients. AB - Certain adverse reactions to aspirin (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs) and pyrazoline derivatives resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions or of the inhibition of the cyclooxygenase pathway of arachidonic acid metabolism leading to an increase in the generation of leukotrienes (LTs) and a decrease in the generation of prostaglandins (PGs) was not fully demonstrated. In this study, two types of specific IgE antibodies have been found in 27 serum samples from 28 ASA sensitive patients with salicyloyl-discs and O-methylsalicyloyl-discs by Radio Allergo Sorbent Tests (RAST). The positive rates were 96.4% and 71.4%, respectively. In contrast, no positive results could be found in 10 normal donors without ASA sensitivity after ingestion of ASA 500 mg/day for 14 days. Further investigation of the chemical structure of epitopes was done by cross inhibition studies. Our results are an increasing evidence in favour of an IgE-dependent mechanism in patients suffering from ASA sensitivity. Hopefully, the determination of specific IgE antibodies will be a safe diagnostic method of ASA sensitivity in vitro. PMID- 1418181 TI - A study on antigenic and allergenic changes during storage in three different biological extracts. AB - The stability of three allergens common in tropical countries was evaluated under different storage conditions. Prosopis juliflora (PJ), Rhizopus nigricans (RN), and wheat dust (WD), were taken as representatives of various groups of allergens viz, pollen, fungi and dust. The extracts were stored in buffer containing phenol (0.4%) or glycerol (50%) at temperatures ranging from 4-55 degrees C for 15 to 60 days. Protein content of PJ extract was reduced remarkably when it was stored at 40 degrees C for 45 days. Thin layer isoelectric focusing and rocket immunoelectrophoresis of PJ showed that certain antigenic proteins degrade rapidly even at 25 degrees C as early as day 15. However, two to three proteins of PJ remain stable at a higher temperature (40 degrees C) for two months. Relative radioallergosorbent test (RAST) inhibition showed substantial loss of allergenic activity in all the three extracts, when stored at higher temperatures (25-55 degrees C) even for short durations, i.e., 15 days. Extracts (PJ and RN) containing 50% glycerol were found to be stable, retaining more than 50% activity, even when stored at 55 degrees C for 40 days, while extracts without glycerol lost more than 75% of their allergenic activity. However, addition of glycerol did not change the stability of wheat dust allergenic extract. The present findings indicate that allergenic extracts behave differently when stored. Hence, the stability of each extract should be determined individually. PMID- 1418182 TI - Dot-blot ELISA for the detection of IgM RF and IgA RF. AB - Dot-blot ELISA was developed for the detection of IgM RF and IgA RF. Normal rabbit IgG (NRIgG), concentration 100 micrograms/ml, was used as the antigen for dotting on the 0.45 microns pore size nitrocellulose membrane. Serum, conjugate and substrate incubation conditions were at room temperature for 1 hour, 1 hour and 3 minutes, respectively. The membrane with NRIgG dot could be sotred for 6 weeks before use in the assay. Positive results of IgM RF, at the serum dilution 1:800, were found in 31/51 patients with either classical or definite rheumatoid arthritis and 3/68 normal healthy individuals. Positive IgA RF, at the serum dilution 1:100, was found in 27/51 of the former and none of the latter. Significant concordance with high agreement index was found between the results of the dot-blot ELISA developed and those obtained from ELISA performed in microtitre plate (Kappa greater than or equal to 0.78 for IgM RF and 0.83 for IgA RF, p less than 0.001). PMID- 1418183 TI - Re-evaluation of ELISA and latex agglutination test for rheumatoid factor detection in the diagnosis of rheumatoid arthritis. AB - An indirect ELISA for the determination of each isotype (IgM, IgG, IgA, IgD, IgE) of rheumatoid factors (RF) was performed with sera obtained from 77 patients with either classical or definite rheumatoid arthritis (RA) and 319 controls, using rabbit IgG as the antigen. The results were compared with those of a commercial latex agglutination test, using denatured human gamma globulin as the antigen for rheumatoid factor determination. At the cut-off level at which positive results were found in less than 5% of normal controls, ELISA for IgM RF determination had sensitivity, specificity, efficiency, positive predictive value and negative predictive value of 46.75%, 98.12%, 88.13%, 85.71%, 88.41%, while those for IgA RF were 46.75%, 93.42%, 84.34%, 63.16%, 87.91% and for IgG RF were 59.74%, 92.16%, 85.86%, 64.78%, 90.46%, respectively. These indices by latex agglutination test were 83.11%, 93.73%, 91.67%, 76.19% and 95.83%, respectively. IgD RF titre greater than or equal to 1:5 was detected in 19/77 RA patients and 4/200 normal controls while IgE RF titre greater than or equal to 1:5 was detected only in 7/77 RA patients. Thus, ELISA did not appear to have any advantage over latex agglutination test for diagnosis of RA. PMID- 1418184 TI - Sinusitis in Thai asthmatic children. AB - The radiographic appearance of sinuses was studied in 146 Thai asthmatic patients aged 1-13 years. Forty-eight percent of cases showed sinusitis by the radiographic criteria. The maxillary sinus was most commonly involved (98.6%). Thirty-three percent had ethmoidal sinusitis and 7% of those with developed frontal sinuses had frontal sinusitis. Thirty-three percent had more than one sinus involved. Those with frontal sinusitis always had maxillary and/or ethmoidal involvement. Sixteen cases had signs and symptoms of sinusitis and all of the cases had the radiographic appearance of sinusitis. There was no correlation between the occurrence of sinusitis and duration or severity of asthma. There was no difference in the occurrence of sinusitis between those with or without allergic rhinitis. No correlation between severity of sinusitis and age of patients was observed. PMID- 1418185 TI - ELISA for seroepidemiological study of exposure to Vibrio cholerae of population in Krabi Province, Thailand. AB - Seroepidemiological study of Vibrio cholerae exposure was carried out in Krabi Province during January 1989 to December 1990 using indirect ELISA to determine serum antibodies to lipopolysaccharides (LPS) of V. cholerae. Among 363 serum samples obtained from cord blood and venous blood of healthy persons, aged from 6 months to over 50 years, 65% and 64% were found positive for specific IgG and IgM against LPS of V. cholerae, respectively. The seroprevalence of V. cholerae infection increased with age from that found at 6 months, being highest in the age groups of 30-49 years for IgG and 15-29 years for IgM. The seroprevalence of V. cholerae infection was higher among female Muslims and home-makers, and increased with the family income. The seroprevalence of cholera infection was also influenced by home location, methods of food storage and water supply. These data suggested that a large number of Krabi's population had V. cholerae infection. PMID- 1418186 TI - Comparison of immunogenicity of hepatitis B vaccine between low and normal birth weight infants. AB - A comparative study was conducted to evaluate the immunogenicity of hepatitis B vaccine in low and normal birth weight infants. Hepatitis B vaccine (Hevac B Pasteur) was given to 50 low birth weight infants and 50 controls, matched by sex and date of delivery. The vaccine was given at birth, 1, 2 and 12 months of age. HBsAg and anti-HBs were assessed at birth, 4, 9 and 13 months of age by the micro ELISA technique. Using the geometric mean titre of anti-HBs and the seroconversion rate as indicators, the immunogenicity of hepatitis B vaccine in low birth weight infants was as good as in normal birth weight infants. PMID- 1418187 TI - Status and trend of HIV-1 infection and AIDS in Taiwan, December, 1991. AB - From May 1, 1985 to December 31, 1991, a total of 4,962,707 serum samples from 8 population groups in Taiwan were tested for anti-human immunodeficiency virus type 1 (anti-HIV-1). In total, 256 samples were seropositive; of these individuals, 43 developed acquired immunodeficiency syndrome (AIDS): 29 were homosexuals; 5 were hemophiliacs; 8 were heterosexuals and 1 was of unknown risk. Although the prevalence of HIV-1 infection and AIDS remains low compared with other countries, since 1988 the increase has been rapid. Before 1977 the majority were homosexuals and hemophiliacs; thereafter the risk groups diversified, with a trend away from homosexuals and hemophiliacs towards heterosexuals and intravenous drug abusers (IVDAs). A few patients have caused serious social problems for the public, health care workers and families. Active community efforts are needed to achieve future success in the control of HIV-1 infection and AIDS in Taiwan. PMID- 1418188 TI - Analysis of antibody levels before and after praziquantel treatment in human paragonimiasis heterotremus. AB - Enzyme immunoassays (ELISA) and Western blot analysis were used to determine IgG antibody levels in patients infected with Paragonimus heterotremus from Thailand before and after treatment with praziquantel. An IgG antibody ELISA showed that a substantial reduction of antibody levels occurred after one year of treatment. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis showed that P. heterotremus adult extract is highly complex, consisting of more than 9 antigenic bands with molecular size ranging from 123 kDa to less than 12.3 kDa. Two prominent bands of 31.5 kDa and 18.5 kDa were found to show consistent reactions with all serum samples from the pretreatment group. There was a marked reduction in the intensity of the reaction of the 31.5 kDa band with each serum sample from post-treatment patients but the other bands disappeared during the one year interval. PMID- 1418189 TI - Transcutaneous gas tensions in the sacrum during the acute phase of spinal cord injury. AB - The first few months following injury to the spinal cord requires constant care of the subject if tissue breakdown is to be avoided. The management of acute traumatic cases involves complete bedrest in a supine position with appropriately positioned pillows to minimize trauma to the bone prominences. This study assesses the effectiveness of the management procedure in terms of the tissue response at the sacrum of 15 acute spinal cord injured subjects. The measurement of mean interface pressures during a representative period of recumbency was performed and these were related to changes in transcutaneous gas tensions (TcPO2 and TcPCO2), which are reliable indices of tissue viability. A series of six variables was established which were compared to each other using non-parametric statistical analyses. It was shown that this group of subjects demonstrated a normal mechanism whereby the level of carbon dioxide was able to control the local vascular tone. The results also suggested that the practice of gapping at the sacrum should be revised to reduce mean sacral pressures and minimize the possibility of tissue breakdown, the risk of which is constant throughout the first three months following injury. PMID- 1418191 TI - A comparison of various loading configurations of the proximal femur for the evaluation of reconstructive surgical procedures. AB - The study was designed to evaluate the effect of different loading configurations on stem and bone stresses in simulated total hip arthroplasty. The traditional experiment design of loading the model through the head of the prosthesis by the resultant joint force was compared with a more realistic model which included an abductor strap to simulate the abductor muscle force. In addition, an alternative experiment design was evaluated in which a loading arm was clamped directly on to the head of the prosthesis. The results show that loading the model by the resultant joint force not only changes the magnitude of the stresses but also the stress distribution compared to the abductor muscle model. The new experiment design closely approximates stresses seen in the abductor muscle model below the lesser trochanter. In the proximal region, the stresses are increased on the medial side and decreased on the lateral side. The advantages of the proposed loading model are: (a) easy and reproducible set-up and alignment is facilitated, (b) different positions of the femur (flexion, extension) can be simulated and (c) a more realistic stress distribution and magnitude is achieved. PMID- 1418190 TI - Reconstruction of the anterior cruciate ligament. AB - Ligaments are strong collagenous structures that act as constraints on joint motion, thus confining the articular surfaces to more or less the same paths. In so doing they prevent arbitrary apposition of these surfaces from occurring and resulting in abnormal stresses which may damage the joint surfaces. Ligaments rupture due to excessive loads, particularly those resulting from trauma occurring during sporting events or motor vehicle accidents. Knee and ankle joints have the highest frequency of ligamentous injuries. This paper is a brief review of the current approaches to the reconstruction of the knee ligaments with specific reference to the anterior cruciate ligament (ACL) being the most frequently reconstructed. This is not only because it is frequently injured but also because of the debilitating consequences of such an injury. Approaches ranging from the conservative to those that advocate the use of frank prosthetic replacement have been adopted by surgeons at both ends of the spectrum. Following a discussion of the rationale for reconstruction of the ACL, the mechanical and biological considerations of the reconstructive procedure are discussed. The different methods of ACL reconstruction are reviewed. These include: (a) primary repair, (b) reconstruction with different tissues, including autogenous allografts and xenografts, (c) reconstruction employing different synthetic devices. A brief discussion of the procedures used for reconstruction with different types of tissue and of the surviving examples of the synthetic devices will follow. PMID- 1418192 TI - The function of bipolar hip prostheses--a laboratory study using cadaveric acetabula. AB - Cadaveric acetabula were mounted in a hip simulator and the friction developed in each during articulation with a series of metal femoral head prostheses of differing sizes was measured. In a separate study, assembled Hastings bipolar hip prostheses were subjected to weight-bearing forces in the same acetabula and their self-righting mechanism was observed. The self-righting mechanism was found to function efficiently, in most cases overcoming the combined friction of the inner and outer articulations of the Hastings hip. However, during motion in the hip simulator a wide variation of friction was observed between different acetabula and within the same acetabulum with differing head size. In several cases this acetabular friction was found to be less than the friction in the inner articulation of the Hastings bipolar hip prosthesis, and this may explain some cases of reported failure of biarticular function. PMID- 1418193 TI - The CADCAM contribution to customized orthopaedic implants. AB - CADCAM (computer aided design/manufacture) production methods are often associated with mass production; working in the medical field at the Department of Biomedical Engineering, the requirement is for one-off, individualized implants. Using a knowledge-based system, implant designs are produced from X-ray data. Assembly from modular components has greatly reduced the production time of implants for bone tumour cases. CADCAM techniques are also used in the production of custom-made hip replacements using digitized data gathered from radiographs. Femoral canal shape is calculated and the optimal implant designed and manufactured from titanium alloy on the Department's CNC (computer numerically controlled) machines. PMID- 1418195 TI - Bioengineering activities in the Department of Mechanical and Production Engineering at the University of Limerick. PMID- 1418194 TI - Revision of cemented fixation and cement-bone interface strength. AB - Interfacial shear strength between poly(methyl methacrylate) (PMMA) bone cement and cancellous bone was measured in bone samples from human proximal femora. Samples were prepared with fresh cement-bone, fresh cement inside a mantle of existing cement and with fresh cement-revised bone surfaces. Push-out tests to measure shear strength caused failure only at bone-cement interfaces; revised bone interfaces were 30 per cent weaker (P < 0.02) than primary interfaces. The clinical relevance is that revision of cemented joint arthroplasties may necessitate removal of components with sound cement-bone fixation. The practice of removing all traces of PMMA cement may not yield the optimal fixation; adhesion of fresh cement to freshly prepared surfaces of the existing cement might also be considered where circumstances are favourable. PMID- 1418196 TI - The mechanics of soft tissues and soft tissue replacements. PMID- 1418197 TI - A model of the geometrical changes in aortic valve leaflets in response to leaflet extension and variable boundary conditions. AB - The function, deformation and performance of heart valve leaflets are dependent on the material properties and the geometry of the leaflet. As the leaflet acts as a constrained membrane the geometry is dependent on the boundary condition applied to the leaflet and any permanent extension of the leaflet. Both of these factors are varied during the preparation of frame-mounted porcine bioprosthetic heart valves and surgical insertion of free-sewn valves. This can result in abnormal geometry and function. A mathematical model has been developed which describes these changes in geometry of a cylindrical leaflet as a function of the diameter of the aortic root (boundary conditions) and the length (or permanent extension) of the leaflet. Both the angle of inclination and the radius of curvature of the cylindrical leaflet were reduced with increased leaflet length or decreased aortic diameter. Agreement was found between the model predictions and experimental observations in porcine bioprosthetic heart valves, where abnormal leaflet geometries are produced by non-physiological boundary conditions and permanent set of the leaflets by fixation with glutaraldehyde. The general solutions developed in this model allow leaflet geometries to be predicted for a range of conditions in free-sewn and frame-mounted valves. PMID- 1418198 TI - AIDS and arthroscopic surgery. AB - There are an estimated 8 to 10 million people worldwide infected with human immunodeficiency virus (HIV). The true extent of infection in the population is unknown, and many are unaware of their HIV status. Arthroscopic and arthroscopically assisted surgery is less invasive and bloody than other orthopaedic procedures, and seemingly less hazardous to surgeons. Nevertheless, the potential for exposure exists. Arthroscopic surgeons routinely experience gown, face-mask and shoe-cover saturation from the splashing of blood-tainted irrigation fluid. Glove perforations by needles, sharps, and bone fragments can occur. Bone and tissue allografts pose risks to both surgeon and patient, as HIV has been recovered from fresh, frozen and freeze-dried specimens. The process of cleaning and disinfecting arthroscopes adequately can damage these expensive devices. This article addresses the safeguards that arthroscopic surgeons should take to prevent exposure to HIV. Effective sterilizing and disinfecting techniques for arthroscopes are also discussed. PMID- 1418199 TI - Arthroscopic microdiscectomy. AB - Follow-up examinations performed a minimum of 2 years postoperatively showed that no neurovascular complications developed in 100 patients who underwent arthroscopic microdiscectomy for treatment of herniated discs at L3-4, L4-5, or L5-S1. By using a posterolateral approach, endoscopic control, and specially designed straight, upbiting, and deflectable forceps, it was possible to remove not only fragments located in the center of the nucleus, but also fragments that had migrated posteriorly and posterolaterally. Analysis of operative results by a modification of the Rush-Presbyterian-St. Luke's lumbar spine analysis system demonstrated that 88 of the patients attained excellent or good results and 12 attained poor or fair results. The outcome of surgery was not related to age, sex, or surgical level. The most common causes of an unsuccessful surgical outcome were lateral recess stenosis and sequestered fragments missed in the preoperative work-up. PMID- 1418200 TI - Arthroscopic therapy of recurrent anterior luxation of the shoulder by capsular repair. AB - Sixty-five cases of recurrent anterior unidirectional dislocation of the shoulder were treated by arthroscopic capsular repair. In this approach, the arthroscope is inserted through a posterior portal. Using mostly an anterior portal, a 5-mm hole is drilled across the neck of the glenoid, between the 3 and 4 o'clock positions. A 5-mm working cannula is passed from the posterior portal into the joint. Mostly through the anterior portal, four to six retention U-sutures are placed in the labrum, the middle and inferior glenohumeral ligament, and the subscapularis tendon. A 25-cm-long, 2.0-mm K-wire with an eye is used. The sutures are pulled out posteriorly through the cannula and tied on the fascia of the infraspinatus muscle. The goal of the procedure is to reattach the detached labrum-ligament complex (LLC) and achieve a capsulorrhaphy in a medial-lateral and superior-inferior direction. There were nine redislocations during a follow up period of 24-60 months (average, 35.3 months). Reasons for redislocation were (a) fewer than four sutures; (b) no sutures of the LLC; (c) placement of the drill hole in the top third of the glenoid; (d) nontraumatic dislocation; (e) no Bankart or Hill-Sachs lesion; (f) transverse tear of the LLC; or (g) technical errors. Redislocation was more common in male patients. PMID- 1418201 TI - Effusions after anterior cruciate ligament reconstruction using the ligament augmentation device. AB - Persistent effusions occurred in 4.3% (seven patients) of 164 patients who underwent anterior cruciate ligament (ACL) reconstruction using an autograft augmented with the ligament augmentation device (LAD) between 1986 and 1989. No bacteria were cultured from the joint fluid. The radiograph in each case showed a tibial drill hole located anteriorly or anterolaterally. Arthroscopy confirmed an abraded LAD in six cases and breakage of the LAD in one case and impingement of the graft on the femoral condyle during extension. Under polarized light microscopy, the histology of the synovia showed foreign body giant cells in one case and particles among the proliferative cells in four cases. The effusions subsided in two cases after notchplasty and in five cases after removal of the LAD. Impingement of the graft on the femoral condyle due to incorrect positioning of the tibial drill hole presumably produced particles that induced synovitis and effusions. PMID- 1418202 TI - Videoarthroscopy: review and state of the art. AB - Since the introduction of videoarthroscopy, there has been rapid technological advancement. The charged couple device (CCD) has become the standard small pickup unit for the present cameras. The video signal processing and transfer has been modified and improved. New Y/C or super VHS and red, green, blue (RGB) systems have been associated with improvements in monitors, video recorders, and video printers. Measurements of video quality such as resolution, signal-to-noise ratio, pixels, and contrast have been confusing to clinicians evaluating these new systems. Equipment compatibility and the weak-link theory is important to understand when selecting new equipment. This review article presents an update for the clinician who wants more information to differentiate among the new video arthroscopic systems. PMID- 1418203 TI - Office arthroscopy: a diagnostic alternative. AB - Twenty patients with enigmatic knee symptoms were selected for evaluation by both magnetic resonance imaging (MRI) and office arthroscopy. Office arthroscopy was performed in a standard examination room using a miniature (1.7 mm) fiberoptic arthroscope under local anesthesia. All MRI scans were performed on a state-of the-art 1.5-T magnet unit, and included specialized cartilage sequences in 7 patients. In 14 patients, 26 areas showed articular cartilage changes by arthroscopy (grade 2-3). Only nine of these areas were detected by MRI (sensitivity 34.6%). There were five false-positive and four false-negative readings of meniscal tears by MRI as compared with office arthroscopy. These results improved when postoperative menisci were excluded. Only one of three anterior cruciate ligament (ACL) disruptions identified by MRI could be verified by arthroscopy. The one posterior cruciate ligament (PCL) disruption was confirmed by both techniques. MRI was superior to arthroscopy in identifying bone contusions, subchondral sclerosis, and medial cruciate ligament (MCL) sprains. Office arthroscopy is an accurate and cost-efficient alternative to MRI in diagnostic evaluation of knee pathology in patients with enigmatic symptomatology. PMID- 1418204 TI - Preoperative computed tomography scanning and arthroscopy in predicting outcome after lateral retinacular release. AB - We initiated a study to look at preoperative, flexed-knee, midpatellar computed tomography (CT) scans and intraoperative arthroscopic findings of lateral patellar articular degeneration in predicting the results after lateral retinacular release for failed nonoperative treatment of anterior knee pain. Twenty patients with 30 painful knees underwent preoperative flexed-knee, midpatellar CT scans that were retrospectively classified by the method of Fulkerson into normal alignment, lateral subluxation, lateral patellar tilt, and combined tilt and subluxation. Arthroscopy was performed before open lateral release. The lateral facet of the patella was graded as either minimal changes (Outerbridge I or II) or advanced (Outerbridge III or IV) changes. Patients were followed for a minimum of 2 years and graded on a standard patellofemoral rating scale. Only 22 of 30 knees that were thought to be clinically malaligned, actually were malaligned by CT scan; eight CT scans were interpreted as normal. The results were further stratified into group A (CT-documented tilt, minimal facet changes), group B (CT-documented tilt, advanced facet changes), and group C (normal CT). Ninety-two percent of group A were rated good or excellent. Twenty two percent of Group B rated good/excellent, 33% fair, 44% poor. Only 13% of group C rated good (one patient). Based on the results of the study, we recommend lateral release for anterior knee patients with CT-proven patellar tilt who have not responded to conservative treatment and have minimal facet changes with minimal or no subluxation. Lateral retinacular release should not be offered as a treatment to the patient with a normally aligned patella because poor results will most likely result. PMID- 1418205 TI - Medial patellofemoral ligament reconstruction for recurrent dislocation of the patella: a preliminary report. AB - We present a surgical technique for the treatment of recurring dislocation of the patella. The procedure, based on Galleazzi's tenodesis of the semitendinosus, uses minimal dissection and small incisions to improve cosmetic results and speed recovery. A polyester ligament is passed through a bone tunnel at the midline of the patella and fixed at the medial condyle, thus creating a medial patellofemoral neoligament. We have reviewed the results of 30 knees in 30 patients with an average follow-up of 39 months. Twenty-five patients (83.3%) showed significant improvement of their initial complaints. PMID- 1418206 TI - Intraarticular pressures in a gravity-fed arthroscopy fluid delivery system. AB - Seven consecutive patients undergoing arthroscopic surgery in a gravity-fed fluid delivery system were studied. The average minimum adequate intraarticular pressure (MAIP) was 55 mm Hg. The height of a saline bag above the knee necessary to achieve this average MAIP was 75 cm. There was a positive correlation between diastolic blood pressure and the minimum adequate intraarticular pressure in this study. There was no positive correlation between systolic blood pressure and the MAIP. PMID- 1418207 TI - Arthroscopic partial meniscectomy: a long-term follow-up. AB - A follow-up study was conducted to clarify the clinical and radiological long term consequences of arthroscopic meniscus resection. One hundred thirty-six patients who had unilateral arthroscopic resection of an isolated meniscal tear attended for an interview and a physical and radiological examination. Follow-up averaged 8.5 years, with a range of 7.9-11.6 years. The reoperation rate was as high as 22.8%, but was the lowest in the bucket handle tear group (13%). Pain after exercise was less frequent among patients treated for a bucket handle tear compared to other lesions. Fifty-three percent of the patients had at least one of the Fairbanks change in the operated knee and only 22% in the control knees. The radiographic result was not influenced by the type of meniscus lesion nor were high age or intraoperatively described cartilage damage factors of significance. Malalignment less than 4 degrees of valgus and greater than 10 degrees of valgus was found to be a significant risk factor for the development of degenerative changes following meniscus resection. PMID- 1418208 TI - Serial magnetic resonance study assessing the effects of impingement on the MR image of the patellar tendon graft. AB - This study was designed to serially analyze the magnetic resonance (MR) appearance of patella tendon grafts during the first year of implantation, and to determine if the sagittal location of the tibial tunnel affects the MR appearance of the graft. An additional goal was to analyze the effect of the sagittal placement of the tibial tunnel placement on knee extension and stability. Two groups were defined by comparing the sagittal relationship of the tibial tunnel to the slope of the intercondylar roof from a lateral roentgenogram of the knee in full extension. The roof impinged group consisted of nine patients who had the tibial tunnel placed anterior to the tibial intersection of the slope of the intercondylar roof. The unimpinged group was composed of eleven patients who had the tibial tunnel placed posterior and parallel to the slope of the intercondylar roof. MR scans were obtained at 0-2, 12, 24, 36, and greater than 48 weeks postoperatively. The signal intensities of grafts in both groups were identical at 1 week, but increased in the impinged group by 3 months and remained increased at 12 months postoperatively (p less than 0.01). In contrast, the MR signal of grafts in the unimpinged group remained unchanged during the first year. Knees with impinged grafts had extension deficits but remained stable. Roof impingement was impossible to view directly with the knee in full extension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418209 TI - Arthroscopic surgery of the knee: its role in the support of U.S. troops during Operation Desert Shield on USNS mercy. AB - The role of arthroscopy in the preconflict deployment of a large number of military troops is not well defined. Between September 1990 and January 1991, while deployed to the Persian Gulf for Operation Desert Shield 73 patients underwent on-board elective arthroscopy on the USNS Mercy. There were 71 men and two women with an average age of 27 years (range 19-47). Indications for arthroscopy included clinical diagnosis of meniscus tear, acute hemarthrosis, chronic effusion, and intra-articular loose body. Findings at the time of arthroscopy included 34 patients (47%) with meniscus tears; 17 (23%) with anterior cruciate ligament tears; five (7%) with isolated grade II-IV chondromalacia involving the patella, trochlea, femoral condyles, or tibial plateaus; six (8%) with synovitis; four (5%) with osteochondritis dissecans of the medial femoral condyle; two (3%) with a medial retinacular tear secondary to patella dislocation; and 10 (14%) with normal arthroscopic examinations. Forty nine patients (66%) were returned to duty at an average of 6 days postoperatively, obviating the need to evacuate these patients from the Middle East theatre. PMID- 1418210 TI - A potential complication of endoscopic carpal tunnel release. AB - Complications of carpal tunnel release have been well documented in the literature. Recently, a procedure for endoscopic release of the transverse carpal ligament has been described. This case report demonstrates a potential complication of endoscopic carpal tunnel release, in which the flexor digitorum superficialis tendon to the ring finger was nearly cut when the arthroscopic trocar passed beneath it. The procedure was converted to an open carpal tunnel release when the transverse fibers of the carpal ligament were not seen after several passes of the trocar. This complication was related to the inability to fully extend the wrist and metacarpophalangeal joints because of arthritic contractures. This case underscores the need for accurate identification of endoscopic anatomy prior to release of the carpal tunnel. The surgeon should not hesitate to convert to open technique if it becomes necessary. PMID- 1418211 TI - Cystic degeneration of the patella after arthroscopic chondroplasty and subchondral bone perforation. AB - Chondromalacia of the patella is frequently encountered in patients with anterior knee pain. Arthroscopic chondroplasty with perforation of subchondral bone remains a popular treatment alternative in spite of the inferior mechanical properties of the fibrocartilaginous tissue that this procedure is designed to promote. We report a case of cystic degeneration of the patella as a previously unrecognized complication following the procedure. PMID- 1418212 TI - Arthroscopic resection of chondroblastoma of the knee. AB - We present a case of chondroblastoma of the upper tibia treated by complete arthroscopic excision. The diagnostic difficulties raised by the case are discussed. This method of treatment has not, to our knowledge, been reported in the literature. PMID- 1418213 TI - Arteriovenous fistula after arthroscopic synovectomy in a patient with haemophilia. AB - Arteriovenous fistula is a rare complication of arthroscopy. We report a human immunodeficiency virus-positive person with haemophilia who 19 months after an arthroscopic synovectomy of the knee presented with increasingly frequent haemarthroses and a palpable thrill over the knee. Angiography confirmed an arteriovenous fistula. The patient was successfully treated by surgical ligation of the communicating vessels. The literature regarding vascular injuries after arthroscopy of the knee is reviewed. PMID- 1418214 TI - Arthroscopic roofplasty: a method for correcting an extension deficit caused by roof impingement of an anterior cruciate ligament graft. AB - Intercondylar roof impingement should be suspected in any patient having difficulty regaining knee extension following an anterior cruciate ligament (ACL) reconstruction. An arthroscopically performed roofplasty can eliminate the clinical complaints. The extent of bone removal can be planned from studying a lateral radiograph taken with the knee in terminal extension. Extension exercises or passive extension devices should not be used in patients with extension deficits caused by roof impingement because they may further damage the graft. PMID- 1418215 TI - Tibial bone plug nonunion: a cause of anterior cruciate ligament reconstructive failure. AB - Anterior tibial tunnel placement contributed to the failure of two previous anterior cruciate ligament reconstructions. An allograft patellar bone-tendon bone nonunion within the tibial tunnel caused dysfunctional ligament laxity. This is the first report of this type of reconstructive cruciate ligament failure. PMID- 1418216 TI - Midcarpal arthroscopy: anatomy and technique. AB - Wrist arthroscopy has had a dramatic impact in both evaluation and treatment of a variety of wrist problems. Wrist arthroscopy has typically meant arthroscopy of the proximal wrist joint; however, midcarpal joint arthroscopy is becoming a routine part of a complete arthroscopic examination of the wrist. Specific indications, pertinent anatomy, and a clear technique for performing a midcarpal arthroscopy is not well documented in the literature. This article attempts to offer some insight on these issues. PMID- 1418217 TI - The Arthroscopy Association of North America: the second decade. PMID- 1418218 TI - Oxidative energy metabolism in Alzheimer brain. Studies in early-onset and late onset cases. AB - Reduction of the cerebral metabolic rate of glucose is one of the most predominant abnormalities generally found in the Alzheimer brain, whereas the cerebral metabolic rate of oxygen is only slightly diminished or not at all the beginning of this dementive disorder. This metabolic abnormality may induce severe functional disturbances, obviously preceding morphobiological changes. From the cerebral metabolic rates of oxidized glucose and oxygen, the cerebral ATP formation rate was calculated in incipient early-onset, incipient late-onset and stable advanced dementia of Alzheimer type. A reduction of ATP formation was found from at least 7% in incipient early-onset, to around 20% in incipient late onset DAT, and from 35% to more than 50% in stable advanced dementia. This approximation was adjusted to findings demonstrating diminished activities of enzymes active in glucose metabolism and formation of oxidation equivalents for ATP production from substrates other than glucose. A reduction for energy formation to the same range was found, as was also recently reported, in vivo in Alzheimer patients. From this rather theoretical point of view, a permanent loss of energy by at least 7-20% in incipient and progressively advancing dementia of the Alzheimer type may be assumed, with an increasing tendency in stable advanced dementia to around 50% energy loss. This energy deficit may have drastic impacts on brain function. PMID- 1418219 TI - Expression of protease nexin-II in human dorsal root ganglia. A correlative immunocytochemical and in situ hybridization study. AB - Protease nexin-II (PN-II) is a potent chymotrypsin inhibitor that forms SDS stable inhibitory complexes with epidermal growth factor binding protein, the gamma-subunit of nerve growth factor, and trypsin, and represents the secreted form of the amyloid beta-protein precursor (APP) that contains the Kunitz-type protease inhibitor domain. To determine the expression of PN-II within the peripheral nervous system, human dorsal root ganglia were processed for immunocytochemistry using well-characterized monoclonal antibodies against PN-II and for in situ hybridization studies using 35S-RNA PN-II probes for both APP751 and APP770. Highly specific immunoperoxidase staining of PN-II was demonstrated within the cytoplasm of dorsal root ganglia neurons and their processes in cryostat (fresh frozen) and vibratome (paraformaldehyde-fixed) sections. In situ hybridization using an anti-sense 35S-RNA PN-II probe demonstrated the presence of intense neuronal labeling. Labeling was not observed when the corresponding sense 35S-RNA PN-II probe was used. Although the precise functional role of PN II/APP is not clear, the accumulation of amyloid beta-protein within the neuropil appears to be one of the earliest events in the pathogenesis of Alzheimer's disease (AD). Thus knowledge of the cell populations expressing the PN-II/APP gene would certainly be helpful for studies of the molecular mechanisms leading to the morphological and functional changes of AD. The results of this study clearly establish the expression of PN-II and its mRNA within the dorsal root ganglia neurons and their processes, and provide another point of departure for studies of the molecular mechanisms underlying the deposition of amyloid beta protein and its relationships to the formation of neuritic plaques and neurofibrillary tangles. PMID- 1418220 TI - Calcium-activated neutral protease (CANP) in normal and dysmyelinating mutant paralytic tremor rabbit myelin. AB - Calcium-activated neutral protease (CANP) in normal and dysmyelinating mutant, paralytic tremor (PT) rabbit myelin and premyelin fractions was studied using immature (4-5 wk) or adult animals. The enzyme was estimated by determination of its catalytic activity as well as by using immunoblot analysis after SDS-PAGE separation. The presence of two forms of CANP--one activated by calcium in the micromolar concentration (mu CANP) range and the other exhibiting low calcium sensitivity in the millimolar concentration range (m-CANP)--was found in the myelin and premyelin fractions. The developmental pattern of the enzyme activity was different for each of these two enzyme isoforms depending on the fraction studied. The higher activity on CANP (both isoforms) found in PT myelin and premyelin could be related to delayed myelination and/or to the higher turnover rate of already formed myelin. These results suggest complex and specific roles for these isoenzymes during myelin formation as is discussed further in this article. Our results confirm the extensive degradation of myelin basic protein (MBP), proteolipid protein (PLP), and, to a lesser extent, the other myelin proteins by endo- and exogenous CANP. This degradation process was significantly elevated in PT rabbit myelin. Moreover as was shown by two-dimensional gel electrophoresis, calcium-controlled proteolysis in nonmutant rabbits affected the net-charge of MBP in a manner similar to that reported for PT myelin, suggesting the possible involvement of CANP in the generation of charge isomers of MBP. PMID- 1418221 TI - Contributions to neurochemical knowledge considered ecologically. AB - The development of neurochemical knowledge is traced through the following stages: (1) Beginnings with academic medicine: a dissertation of 1719, (2) Relations with chemistry and scientific journals of around 1800, (3) A review and the naming of neurochemistry in 1856, (4) Government publication of neurochemistry; a full-time chemist of the brain, (5) Success in a biochemical environment, 1900-1940, (6) Neurochemistry with the neurosciences, (7) Neurochemical environments of 1955-1957. PMID- 1418222 TI - Ganglioside distribution in murine neural tumors. AB - The ganglioside composition of seven experimental brain tumors was examined in C57BL/6J mice. The tumors were produced from 20-methylcholanthrene (20-MC) implantation into either the cerebrum or cerebellum and were maintained in serial transplants through many generations. The tumors studied were grown subcutaneously as solid tumors, and cells from two of the tumors were also studied in culture. Histologically, all of the tumors were similar and could be broadly classified as highly malignant, poorly differentiated anaplastic astrocytomas. The total ganglioside sialic acid content of the solid tumors was markedly lower than that in adult mouse brain. In addition to N-acetylneuraminic acid (NeuAc), the gangliosides in the solid tumors contained significant amounts of N-glycolylneuraminic acid (NeuGc). The seven solid tumors fell into two general groups with respect to ganglioside composition. Furthermore, the differences in ganglioside composition between the two tumor groups were strongly associated with differences in tumor cell cohesion. The tumors in one group had high levels of GM3 hematosides, low levels of oligosialogangliosides, and grew as firm cohesive tissues. The tumors in the other group, however, had lower levels of GM3 hematosides, noticeable amounts of oligosialogangliosides and grew as soft noncohesive tissues. In culture, clonal cells from one of the tumors in the first group grew as clumps or islands and contained GM3 as the only major ganglioside, whereas clonal cells from a tumor in the second group grew as sheets or monolayers and contained little GM3, but expressed several gangliosides with complex structures. In marked contrast to the gangliosides in the solid tumors, the gangliosides in the cultured tumor cells contained trace amounts of NeuGc. Since NeuGc containing gangliosides are abundant in mouse nonneural tissues, the high content of NeuGc gangliosides in the solid tumors may arise from infiltration of nonneural tissue elements, e.g., macrophages, lymphocytes, and endothelial cells. PMID- 1418223 TI - The effect of lipoproteins on human glioblastoma growth in vitro. AB - Experiments were performed using an established human glioblastoma cell line to determine the effect of lipoproteins on regulating their growth. It was found that synthetic and natural human high density lipoproteins (HDL) were effective in inhibiting tumor cell growth in a nontoxic, dose-dependent manner, and that the LD50 was 10-fold lower than that for normal rat astrocytes grown under identical conditions. In the presence of the antioxidant, glutathione, essentially all of the growth-inhibiting properties of HDL could be reversed suggesting that oxidized lipids from the HDL interacting with the plasma membranes of the glioblastoma cells were responsible for the growth-inhibiting effect observed. The markedly lower concentration of HDL required to inhibit glioblastoma cells in culture compared to normal astrocytes suggested that the mechanism of HDL-induced inhibition may be important for tumor growth in vivo. One possible mechanism under investigation is the possibility of HDL modulation of a membrane-associated, tumor-specific phosphatase. PMID- 1418224 TI - [Legal cases on the correlation between exposure to asbestos fiber dust and laryngeal cancer]. AB - In Germany the causal relationship between laryngeal carcinoma and occupational exposure to asbestos is under discussion. We report on 30 cases of laryngeal carcinoma for which compensation was considered, since an occupational contact with asbestos was confirmed or suspected. We looked especially for signs of non tumorous lesions related to asbestos exposure in radiography or CT of the chest. Such signs could be detected in 12 individuals. In Germany compensation for an occupational disease can be granted only, if e.g. the relevance of asbestos exposure is sufficiently probable, with special regard to other noxious influences such as cigarette abuse. Asbestosis of the larynx cannot be diagnosed specifically; we, therefore suggest proving the relevance of asbestos exposure in respect of signs of tumorous or non-tumorous lesions in the chest. PMID- 1418226 TI - [Nystagmus reactions after rotatory vestibular stimulation (modified Veits long term rotation) in patients with normal equilibrium. Part I: Absolute values of the nystagmus reactions]. AB - In this study the nystagmographic findings of 70 healthy subjects--obtained after having used the rotatory test (modified method of Veits)--are summarised and visualised by means of easily appreciated graphs. In accordance with the recommendations of the ADANO, the test was carried out as a continuous turning of the chair, first clockwise and then counterclockwise, with an accelerating stimulus of 3 degrees/s2 and a sudden stop after a period of constant rotation with a speed of 90 degrees/s (trapezoidal stimulus). This was done for the absolute values of the following nystagmus parameters: frequency, amplitude and slow phase velocity of the nystagmus reaction. The limits of a normal nystagmus reaction are evaluated by the 5%- or 95%-percentiles on the one side and the mean values combined with the standard deviation mean value +/- 2 standard deviations on the other. It is shown that the rotatory test with its different phases enables very sensitive selection between healthy subjects and patients with an acute peripheral vestibular lesion. The intraindividual variability of the nystagmus reactions proved to be lower than that between our control persons (interindividual variability). By our method of employing the rotatory test it can be shown that the interfering phenomenon of habituation does not influence the nystagmographic results. PMID- 1418225 TI - [Mucoepidermoid cancer of the larynx. Case report and review of the literature]. AB - Mucoepidermoid carcinoma (MEC) is classified among the salivary gland tumours and is most commonly found in the parotid gland. It rarely occurs in the larynx. There have been only 87 cases of laryngeal MEC reported in the literature. We report on an MEC of the vocal cord in a 75-year-old man, with a thickened right vocal cord without any loss of movement. The initial diagnosis was squamous cell carcinoma. One year after radiotherapy a tumour recurrence developed. Because the patient refused to laryngectomise, a tumour resection with the CO2 laser was performed twice. To date, the patient has been free from disease for more than five years. The true incidence of this type of neoplasm could be higher than is believed because of its frequent misdiagnosis as squamous cell carcinoma. PMID- 1418227 TI - [Histological studies of the behavior of the dentin ossicular prosthesis in the human middle ear]. AB - The Dentine Ossicular Prosthesis (DOP)--introduced in the ENT-Department, University of Hamburg in 1986--has proved its worth clinically in more than 300 cases. In the meantime six of the prostheses had to be removed for various reasons. They had remained in the middle ear over a period between 2-5 and 47 months. The prostheses were investigated undecalcified by the Donath sawing and grinding technique. Prostheses in a nearly bland surrounding show a partial invagination in fibrous connective tissue without severe reaction of the prosthesis itself, whereas in prostheses removed from the neighbourhood of inflammatory processes or recurrent cholesteatoma a partial resorption of dentine with subsequent new bone formation could be observed. Due to the trouble-free clinical and histological performance in the human middle ear, the Dentine Ossicular Prosthesis can be well recommended as an alternative material in ossiculoplasty. PMID- 1418228 TI - [Acute tonsillitis--peritonsillitis--paratonsillar abscess: Differential diagnosis by flexible endosonography]. AB - The role of flexible endosonography in diagnosis of acute tonsillitis and their complications was investigated in 59 patients. Our results show that flexible endosonography enables the examiner to differentiate acute tonsillitis from peritonsillitis and paratonsillar abscess. In particular, abscesses of retrotonsillar spread possibly leading to life-threatening complications can be detected in an early stage. PMID- 1418229 TI - [The diagnostic value of nuclear magnetic resonance tomography in Sjogen's disease]. AB - Sjogren's syndrome is characterised by xerostomia, xerophthalmia and recurrent parotid swelling. There is a high coincidence with rheumatoid diseases. A variety of clinical and laboratory parameters offers important information for diagnosis, but none of them is specific for this disease. 36 patients with clinical diagnosis of Sjogren's syndrome were examined in a prospective study to evaluate the diagnostic significance of this technique. 34 patients showed an inhomogeneous, nodular pattern in the parotid gland. The signal intensity was very high, especially in the T2-weighted sequences. There was a significant correlation of the radiologic changes with the course of the disease. Four patients with the clinical diagnosis of sialadenosis demonstrated bilateral enlarged glands with a homogeneous signal pattern. Patients with acute purulent parotitis demonstrated enlargement of the gland without an alteration in the signal pattern. Patients with chronic recurrent parotitis and patients with radiogenic sialadenitis showed little inhomogeneous increase of signal intensity. Our results indicate that MRI is presently the radiological method of choice in the evaluation of Sjogren's syndrome. PMID- 1418230 TI - [Evoked otoacoustic emissions as a screening test for hearing evaluation in newborn and premature infants?]. AB - The purpose of this study was the evaluation of evoked otoacoustic emissions (EOAE) for the screening of infant hearing. EOAE and brainstem-evoked response audiometry (BERA) were performed in 40 infants at a special care unit at the Universitats-Klinik, Gottingen. Both examinations were performed under non optimal conditions, reflecting a realistic screening situation. The purpose was to determine robust analysis criteria and possible error sources. A comparison of both tests shows that sensitivity and specificity are insufficient for reliable screening. The EOAE test does not yield the threshold of hearing. There is no sharp boundary with the BERA threshold for the detectability of an EOAE. Sensitivity and specificity have not been accurately determined so far due to the relatively small number of infants with impaired hearing tested. Nevertheless, the results show that EOAE should be applied as a supplement to conventional audiometry for infants. It is capable of excluding conductive and severe cochlear hearing losses and is by itself not a reliable screening test. PMID- 1418231 TI - [Comparative speech audiometry studies with compact disk]. AB - We compared the results of speech audiometry, performed with recorded tape and CD, respectively, in 21 subjects with bone conduction hearing loss, and in 27 subjects with sensorineural hearing loss. In all cases, speech audiometry was performed by using the German Freiburg speech test material, recorded in 1969 on the basis of the German DIN standard 45626. In subjects with an air-bone gap, the hearing loss for speech is 2.3 dB smaller if tested by use of CD, and the speech recognition is 10.5 points better, respectively. Smaller differences could be found in sensorineural HL: For CD, the hearing loss is 1.2 dB smaller, and the speech recognition score is raised by only 1 point. These differences are statistically not significant, and the calculation of hearing impairment and individual hearing handicap from the tables commonly used in Germany in medicolegal expert opinions must not be corrected, if records on CD are used basing on the recordings from 1969 according to DIN 45626. The handling of compact discs has many advantages in relation to the handling of tapes. PMID- 1418232 TI - [Norrie-Wardburg syndrome]. AB - We describe a case of a 25-year old patient with typical Norrie-Warburg Syndrome. From the first year of his life he was found to be blind, with bilateral sensorineural loss of hearing. Audiological examination showed symmetrical moderate bilateral sensorineural hearing loss. His hearing loss was refractory to treatment for the last eight years. Because of timely diagnosis of hearing loss and timely fitting of a hearing aid, the patient could study at school and graduate from university education. Disease carriers who are clinically healthy can be identified only via chromosome analysis. PMID- 1418233 TI - [Morphologic aspects of the maturation of the sensory areas of the cerebral cortex exemplified by the visual cortex of the rabbit]. AB - When the cerebral cortex commences its earliest functional tasks, the cellular layers and the basic organisation pattern of cell processes have already developed. In the rabbit visual cortex it could be shown that the functional differentiation runs parallel to an increase in number and growth of cell processes. Those tissue compartments where the newly formed branches of the dendritic trees of cortical neurons come into contact with the axons arising from other cerebral regions, grow between two and six times larger depending on the cortical layer where their volume fractions are measured. Cell processes grow and increase in number most rapidly between the second and the fourth postnatal weeks. Myelination of fast conducting axons takes longer and attains an adult level about three month after birth. Then the visual cortex of the rabbit may be regarded as mature with regard to both structure and function. PMID- 1418234 TI - [Parallel compensation for independent services i.S.v. section 4 Abs.2 GOA within the scope of strumectomy]. PMID- 1418235 TI - Renaissance for hapten-specific T lymphocytes: implications for basic and applied research. AB - Protein-reactive chemicals and drugs (haptens), such as dinitro- (DNP) or trinitro-phenylated (TNP) reagents or penicillins, are potent inducers of allergic reactions in experimental animal systems as well as in humans. Hapten specific T lymphocytes are mediators of these disorders. Like other antigens, hapten determinants on target cells are recognized by the T cell's antigen specific receptors exclusively in association with gene products of the major histocompatibility complex (MHC). Until recently, the nature of the complex hapten/MHC determinants remained unknown. Atypically, this fact, rather than spurring scientific investigations, caused a rapid loss of interest in haptens as T cell antigens by the majority of immunologists. This situation may now be changing, since we have recently identified MHC-binding, hapten-modified peptides which mediate cellular recognition by T cells via their antigen-specific receptors. Synthetic hapten-peptide conjugates open up new routes in studying the molecular details of hapten recognition by T cells. They may also contribute to a better understanding of what defines an antigen as an allergy-inducing "allergen". PMID- 1418236 TI - 7-Desmethyl-microcystin-RR, a hepatotoxin from a waterbloom of Microcystis aeruginosa. AB - A peptide toxin was isolated from a waterbloom of Microcystis aeruginosa from Lake Froylandsvatn in Norway. The isolation procedure included liquid and solid phase extraction and reversed phase high performance liquid chromatography. Amino acid analysis yielded D-glutamic acid, D-erythro-beta-methylaspartic acid and D alanine in equimolar and L-arginine in twofold molar ratios. The presence of dehydroalanine was confirmed by hydrogenation and subsequent amino acid analysis with combined gas liquid chromatography/mass spectrometry. Investigation of the toxin with fast atom bombardment mass spectrometry showed a nominal relative molecular mass of 1023. 3-Amino-9-methoxy-2,6,8-trimethyl-10-phenyl- 4,6 decadienoic acid (Adda) was identified by 1H NMR and 1H, 1H COSY spectroscopy. The structure of the toxin was elucidated as 7-desmethyl-microcystin-RR. PMID- 1418237 TI - Ferredoxin-NADP+ oxidoreductase of C. paradoxa nucleus encoded, but cyanobacterial gene transfer from symbiont to host, an evolutionary mechanism originating new species. AB - The nucleus encoded cyanoplast ("cyanellar") ferredoxin-NADP + oxidoreductase (FNR) of Cyanophora paradoxa, characterized by an N-terminal amino acid sequence, is compared with homologous sequences of other photoautotrophic organisms. The high degree of similarity to the cyanobacterial sequences indicates a cyanobacterial origin. This could be a first direct demonstration of an intertaxonic combination: a gene transfer from an original endocytobiont (cyanobacterium) to the nucleus of its host, one of the most important demands of the Endosymbiosis Theory, an evolutionary mechanism leading to the origin of a new species. PMID- 1418238 TI - Non-essential activation of rat liver porphobilinogen-deaminase by folic acid. AB - This report demonstrates the ability of folic acid to activate rat liver porphobilinogen-deaminase (PBG-D). Lineweaver-Burk analysis revealed an increase in Vmax (38%) without affecting the Km. In the concentration range assayed, secondary replots of 1/delta slope and 1/delta intersect versus 1/[folic acid] yielded straight lines, indicating the binding of a single molecule of activator to the enzyme PBG-D, with a KA = 1.66 mM. Results presented here show that folic acid acts as a non-essential activator (alpha = 1; beta = 1.6). The activating effect of folic acid has been observed employing the 35-70% ammonium sulphate precipitated fraction, desalted by dialysis or gel filtration, whereas no action was detected when other partially purified PBG-D preparations were utilized as the enzyme source, suggesting either the presence of sites saturated for the activator, or the existence of a different structural protein conformation, or both. PMID- 1418239 TI - Effects of chloroquine on the photosensory membrane turnover and the ultrastructure of lysosome-related bodies of the crayfish photoreceptor. AB - The effect of chloroquine in combination with bright light on the ultrastructure of crayfish (Orconectes limosus R.) photoreceptors was investigated in vivo. Chloroquine had several effects upon the crayfish retina. Multivesicular bodies (MVB) that are involved in lysosomal degradation of photosensory membrane were altered in ultrastructure. MVB frequently contained smaller MVB in a state of more advanced membrane degradation. Additionally screening pigment-like granules appeared in MVB. MVB accumulated in and filled the retinular cell cytoplasm just proximal or distal to the basement membrane which indicated inhibition of photosensory membrane degradation. Under chloroquine treatment rhabdom degradation appeared to be inhibited, as rhabdom diameter was less reduced under these conditions. Also chloroquine caused accumulation of screening pigment granules in glial cells within the lamina ganglionaris. PMID- 1418240 TI - Modulation by ryanodine of active calcium loading and caffeine induced calcium release of heavy sarcoplasmic reticulum vesicles. AB - The effect of ATP on the calcium release channel in heavy sarcoplasmic reticulum vesicles modulated by ryanodine has been analyzed by monitoring active calcium uptake and caffeine induced calcium release under near physiological conditions. Native as well as ryanodine reacted vesicles display a complex time course of calcium uptake resulting in nearly complete exhaustion of medium calcium when ATP in combination with an ATP-regenerating system, in contrast to ATP alone, or dinitrophenyl phosphate, were used to support calcium uptake. Applying of dinitrophenyl phosphate as energy yielding substrate, not affecting channel activity, allowed to estimate the fraction of light vesicles devoided of calcium channels contaminating the heavy preparation as the fraction that stores calcium after the preparation has been treated with channel opening, low concentrations of ryanodine (1 microM). Calcium uptake by contaminant light vesicles (25%) cannot account for calcium storage, as well as, abolition of caffeine induced calcium release of ryanodine treated heavy vesicles. Calcium uptake of native and ryanodine treated vesicles is accompanied by the uptake of equivalent amounts of inorganic phosphate arising from ATP hydrolysis indicating that calcium is mainly stored as calcium phosphate. The momentary capability of the preparation to accumulate calcium was measured by activating calcium uptake during the calcium storage period with 0.2 mM 45CaCl2 and 4 mM phosphate at short time intervals. A significant increase of the momentary uptake activity with time was observed being more pronounced for ryanodine treated than for native vesicles indicating that under regenerating conditions, ATP can induce closing of the native and even more effectively of the ryanodine modified calcium release channels. PMID- 1418242 TI - Maturation and responsiveness to extracts of corpora allata from male Locusta migratoria containing allatotropic factors. AB - Corpora allata (CA) from male Locusta migratoria were tested for their ability to synthesize juvenile hormone (JH) and to respond to stimulating brain/corpora cardiaca (CC)-extracts under in vitro conditions. We found that a preincubation of the CA of both sexes at 4 degrees C for 24 h lowers their basal rate of synthesis and retains their responsiveness to allatotropic factors. Male CA can be stimulated by brain/CC extracts as well as female CA. JH biosynthesis stimulating factors are also present in male brain/CC extracts. Thus such extracts from male locusts can be used for the isolation of locust allatotropin. Furthermore male locust CA are appropriate for bioassaying such allatotropic factors. PMID- 1418241 TI - Modulation by monovalent anions of calcium and caffeine induced calcium release from heavy sarcoplasmic reticulum vesicles. AB - Both calcium and caffeine induced calcium release from actively loaded heavy sarcoplasmic reticulum vesicles were studied to analyze the dependence of both activities on the composition of the release medium with respect to monovalent anions. Calcium is unable to induce net calcium release while caffeine remains effective as releasing agent when the experimental media contain neither chloride nor nitrate ions. Caffeine induced calcium release is not suppressed by chelating residual medium calcium (approximately 0.5-1 microM) with 2 mM EGTA added 15 s prior to 10 mM caffeine. Calcium release from vesicles loaded in media containing 0.2 M gluconate as monovalent anion is induced when the medium is supplemented with chloride or nitrate. The release amplitude increases linearly when K gluconate is replaced by KCl. At constant ionic strength the release amplitude becomes maximal at a chloride concentration of 0.2 M. The chloride effect completely disappears when 2 mM EGTA are added simultaneously. When chloride is replaced by nitrate, as releasing agent, maximal release is achieved already by addition of 0.1 M K-nitrate. The releasing effect of nitrate can only partially be suppressed by EGTA. The different effectiveness of gluconate, chloride and nitrate as calcium release supporting ions corresponds to their activating effect on the binding of ryanodine to the calcium release channel in the vesicular membranes. PMID- 1418243 TI - Evidence for a pathway of distal screening pigment granules across the basement membrane of the crayfish photoreceptor. AB - The distal pigment cells of Orconectes limosus contain two layers of large electron lucent vacuoles that are separated by layers of small right-angled platelets adjacent to the crystalline cones. The crystalline cones of the dioptric apparatus of this species have evaginations into the distal pigment cell cytoplasm. In photoreceptors of Orconectes limosus and Procambarus clarkii a dark pigment accumulation site was detected just distal to the basement membrane at the edges of each retina. These pigment accumulations occurred independent of the state of light adaptation. Ultrastructurally the pigment granules at this accumulation site resemble distal screening pigment granules according to their size (up to 1.2 microns in diameter) and fibrous structure. Distal screening pigment granules were also found in tube-like cell processes or extracellularly within and proximal to the retinal basement membrane, indicating pigment transport to and across the basement membrane. Proximal to the basement membrane screening pigment granules were also observed disintegrated to a gravel-like electron dense material in widely branched cells. Evidence was found that an electron dense material, probably resulting from disintegrating screening pigment granules, was incorporated in the integument of the eyestalk. Four hours after injection of gold particles into the eye stalk distal to the retina they were detected inside and proximal to the retinal basement membrane. PMID- 1418244 TI - Fluorescence of chromatin DNA by an oxazolium scintillator. AB - Aqueous solutions of a yellow and highly fluorescent derivative from dimethyl POPOP, obtained by treating a chloroform solution of this oxazole scintillator with dimethylsulfate, induce a strong blue-green or yellow-green fluorescence in chromatin DNA under ultraviolet (365 nm) or violet-blue (436 nm) excitation, respectively. It is suggested that this new and selective fluorescence reaction could originate from binding of the oxazolium derivative into the minor groove of DNA. PMID- 1418245 TI - O6-alkylguanine-DNA alkyltransferase in the chick embryo during development. AB - In the whole embryo, O6-alkylguanine-DNA alkyltransferase (AT) activity increased until day 9 of development and declined sharply after day 13. AT activity of the liver was greatest between day 12 and day 20 and decreased fast after hatching. In the brain, AT activities reached a maximum at day 17 and 18 and declined sharply after hatching. At two developmental stages with different AT activities (day 10 and day 17) DNA alkylation in the brains was estimated 6, 12, 24 and 48 h after administration of N-methyl-N-nitrosourea in ovo by viscometric measurement of DNA fragmentation. The high AT activities of the chicken embryo brain at the 17th day of development correlated with minor DNA fragmentation following a repair period of 12-24 h. It is suggested that the high basal level of AT in the chick embryo might have a protective function against the persistence of the genotoxic lesion O6-methylguanine during development. PMID- 1418246 TI - Lowell T. Coggeshall and American Medical Education: 1901-1987. AB - This essay analyzes Lowell T. Coggeshall's impact on American medical education by focusing on Coggeshall's 1965 report to the Association of American Medical Colleges (AAMC), Planning for Medical Progress through Education. Coggeshall graduated from medical school in 1928 and became an expert on tropical diseases. During his military experience in World War II, Coggeshall shifted his focus to administration. He was a skilled executive and became well acquainted with the ways of both the federal government and academic medicine. The AAMC, founded in 1876, was a kind of informal "deans' club" for many years. The many social and medical changes of the 1950s and 1960s prompted the AAMC to form a committee, headed by Coggeshall, whose chief task was to provide guidance for the AAMC. The 1965 report recommended that the AAMC move its headquarters to Washington, D.C., and take a more active role in shaping national health policy. However, many of the report's suggestions were not implemented, such as having the AAMC change its name and represent not only medical schools but all health-related academic units. While the report was widely praised, it was also strongly opposed by some powerful groups. This essay reviews the impact of Coggeshall's report and examines the nature of such reports in general. Coggeshall's greatest contribution to American medical education was his role in reshaping the AAMC into an effective voice for academic medicine. PMID- 1418247 TI - The "health of the public" approach to medical education. AB - The author examines the growing discontinuity between medical education and the general health needs of society. He explains and illustrates this failure of the academic medical center in several ways: by a parable; by reporting the results of his informal survey of faculty and residents; by presenting the findings of an international conference on medical education; and by giving a detailed description of the design and impact of the "Health of the Public" program, launched by the Pew Charitable Trusts and the Rockefeller Foundation in 1986. He maintains that there is an imbalance in the training of physicians and other health professionals because academic medical centers are dominated by supply side thinking--which is driven by new knowledge and technology and the resulting need to find patients to fit the interests and technical capabilities of specialists and the equipment and services of hospitals--and have under emphasized demand-side thinking, which concerns the patient and the health expectations, needs, and trends in the community. The author maintains that academic medical centers can continue to achieve the recognition they seek, but can do so by making the changes needed to better balance the driving forces of supply and demand. Only by doing this will they fulfill their fundamental mission of fostering the health of the public. PMID- 1418248 TI - The coming influence of a social sciences perspective on medical education. AB - Medical education will change from within in response to continued advances in biological sciences and technology, but changes that are occurring outside the natural sciences can have greater impact, especially (1) the reconceptualization of the meaning of health, (2) the increase in the number and range of different health improvement strategies, (3) the growing awareness of the paradox of the relatively low health status of the U.S. population and high per-capita and national health care expenditures, and (4) shifts in the causes of illness and death. These changes make it necessary for medical students to be given a foundation in both the natural and the social sciences, for most ill health has causal roots in both the social and physical environment, even though it is not understood how some of these outside influences are translated into disease or biologic derangements that lead to disease. Consideration should be given to changes in medical education that include (1) interpreting the sociology as well as the biology of health, (2) expanding the horizons of medicine to incorporate health improvement as well as disease cure, (3) training for population-based health care at the community level, and (4) learning to assess medical outcomes with more than biometric measures to include measurements of functioning and well being. The author presents in detail a health input-output model to show the complex interrelationships of socio-ecologic (i.e., outside) factors and the individual's genetic-biologic makeup (inside factors) that determine the individual's state of health. PMID- 1418249 TI - Preventing the decline of academic medicine. AB - Academic medicine in North America has been highly successful in many ways in the last 50 years, including being able to resist change while unprecedented and fundamental changes are taking place in the practice, technology, and financing of medicine. This stance places academic medicine at risk of being bypassed by events. To prevent this, what balance between rigidity and flexibility should be sought? The author addresses this question by first reviewing the history of academic medicine and then defining in detail three current problems in medical education and two in biomedical research, two of academic medicine's domains. All these problems have in common some form of harmful dissociation of endeavors: for example, in education, there is a dissociation between both the teaching and academic clinical practice of medicine and the health care needs of the public. The author then proposes solutions to the problems, based on his examination of three major principles that motivate academic medicine. For example, he maintains that the teaching of all the medical sciences should be part of, and equal in quality to, the overall program of sciences in a university, and that the interdependence of medical schools and universities should be nurtured. He also maintains that the narrow conceptual framework of medicine that focuses on mechanisms of disease must be expanded to include rigorous attention to such areas as prevention, technology assessment, and organization of care.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418250 TI - Flexner's model and the future of medical education. AB - Less attention has been paid to Flexner's educational philosophy as compared with the recommendations he made to reform American medical education in Bulletin No. 4 of the Carnegie Foundation, the so-called "Flexner Report." His philosophy begins with the education of the child, having much in common with the educational theories of John Dewey, and is based on learning by observing and doing. Flexner believed that all education should be utilitarian and should prepare the individual for the responsibilities of citizenship and for an occupation or a profession. He also believed that general education lasted too long in this country. Based on Flexner's educational philosophy rather than the four-year medical school model that bears his name, the education of the physician is reexamined. Recommendations are made concerning the interface between the last two years of college and the first two years of medical school that would better equip the future physician to face the complexities of medical practice in the next century. Further, if medical schools were given responsibility for graduate medical education, as has been recommended by prestigious committees in the past, it would be possible to integrate the medical school clinical years with those of residency training and thereby improve the educational experience. A consideration of the education of the physician as a continuum, beginning in the third year of college and ending with the conclusion of residency training, also would be entirely consistent with Flexner's educational views.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418251 TI - Using workshops to teach residents primary care procedures. PMID- 1418252 TI - Medical education reform: the need for global action. PMID- 1418253 TI - The National Health Service Corps: bridging the gap in health care. PMID- 1418254 TI - Helping residents' families cope. PMID- 1418255 TI - Another view of limiting residents' work hours. PMID- 1418256 TI - The need to foster students' research skills. PMID- 1418257 TI - Need for more research about residents' gender, cultural roles, and stress. PMID- 1418258 TI - Advantages of a PBL approach in teaching genetics. PMID- 1418259 TI - Academic achievement and acceptance rates of underrepresented-minority applicants to medical school. AB - While the participation of minority groups underrepresented in medicine has increased from 3% of first-year enrollment in 1968-69 to 11% in 1992, many have been concerned that the percentage of underrepresented-minority applicants accepted is smaller than that of other applicants. To investigate the relationship of acceptance rates and measures of academic achievement, historical data from 1978-79 through 1991-92 on applicant characteristics maintained by the Association of American Medical Colleges were used to develop statistics on acceptance rates for underrepresented minorities and for other applicants, by each applicant's mean score on the MCAT (Medical College Admission Test) and undergraduate science grade point average. Those statistics were then related to trends in applicant numbers. Results show that acceptance rates for both underrepresented minorities and others increased as the numbers of applications from both groups declined, then decreased as applications again rose. When underrepresented-minority applicants were compared with other applicants within the same ranges of grades and MCAT scores, underrepresented-minority applicants were accepted at substantially higher rates in every stratum. Thus, medical schools generally are acting affirmatively in selecting applicants from underrepresented-minority groups. PMID- 1418260 TI - A pilot study of biomedical trainees' perceptions concerning research ethics. AB - The authors surveyed 2,010 biomedical trainees in the fall of 1990 at the University of California, San Diego, regarding their perceptions about unethical practices in research and the extent of their training exposure to the ethics of scientific investigation; 549 responded, representing both clinical and basic science departments and including graduate students and postdoctoral fellows in addition to medical students, residents, and fellows. Of the 549 trainees, 129 (23%) responded that they had received no training in research ethics; 195 (36%), that they had observed some kind of scientific misconduct (although not necessarily in the sense of research fraud defined in federal regulations); and 81 (15%), that they would be willing to select, omit, or fabricate data to win a grant or publish a paper. The trainees planning an academic career were more likely to report having been aware of others' scientific misconduct. Reported exposure to ethics training was not associated with a difference in past or potential unethical behavior. The authors conclude that while the apparent ineffectiveness of past ethics instruction does not preclude the possibility that more systematic training may be useful, it does underscore the need to assess the efficacy of training activities. PMID- 1418261 TI - Physicians, preventive care, and applied nutrition: selected literature. AB - The authors review a core of 25 articles (dating from 1982 through 1991) regarding medical school curricula and physicians' knowledge, attitudes, and practices related to nutritional care, with a focus on prevention of coronary heart disease through cholesterol control. They supplement this review by discussing the relation of the core articles' results to those of additional articles, which focus more generally on physicians' health promotion and patient counseling. While there appear to be modest increases in attention to nutrition at various levels of medical training and some improvement in physicians' attitudes about dietary intervention, the authors conclude that both educational opportunities and physicians' practices warrant increased and more effective attention to nutrition. Finally, in light of recent trends and growing efforts to better prepare physicians to play a leading role in preventive care, the authors identify gaps in physicians' training and in research on physicians, preventive care, and applied nutrition. PMID- 1418262 TI - Combined-degree programs: a valuable alternative for motivated students who choose medicine early. AB - The author reviews the history and philosophy of combined-degree programs and summarizes research on the performances of students in these programs. He notes that about one-fifth of U.S. medical schools offer programs that integrate premedical and medical school studies and lead to the award of both an undergraduate and an M.D. degree in six to eight years. The students in these programs perform as well as students electing traditional programs, if not better. The author concludes that university-affiliated medical schools might well consider establishing combined-degree programs as a means of (1) achieving better integration of the premedical and medical curricula and (2) allowing greater access to combined-degree programs for students mature enough early on to select careers in medicine. PMID- 1418263 TI - Curricular variations in combined baccalaureate-M.D. programs. AB - The authors review curricular characteristics of combined baccalaureate-M.D. programs at 28 U.S. medical schools from 1961, when the first programs started, until 1991-92. Initially, in the 1960s, these programs were created (1) to offer talented high school graduates an accelerated track leading to the baccalaureate and M.D. degrees, (2) to reduce educational expenses, (3) to improve education in the humanities, and (4) to attract outstanding students into careers in medicine. In the 1970s these objectives were modified to address national health care needs, particularly the need to graduate more physicians more quickly, especially primary care physicians for underserved areas. In the 1980s the objectives were broadened to achieve more diverse goals, including emphases on the humanities, community medicine, and biotechnology, in addition to the continued stress on the education of primary care physicians. PMID- 1418264 TI - The Jefferson-Penn State B.S.-M.D. program: a 26-year experience. AB - Since the 1960s a number of physicians have completed both their baccalaureate and their M.D. degrees in six or fewer years. In this longitudinal study the authors track the academic performances, clinical ratings, and career follow-up data of 659 students in one of these accelerated programs, the Jefferson Medical College-Pennsylvania State University B.S.-M.D. program, from entering years 1964 through 1989. The medical school performances, clinical performances in residencies, and rates of board certification and faculty appointment of the accelerated students compared favorably with those of a control group of medical students with similar high school credentials who had followed a four-year baccalaureate program. The authors conclude that a carefully chosen group of students can achieve high academic standards in an accelerated medical school program, graduate as younger physicians able to perform well in postgraduate training, and go on to highly productive careers in medicine. PMID- 1418265 TI - Specialty preferences of graduating medical students: 1992 update. PMID- 1418266 TI - Expert systems in histopathology. V. DS theory, certainty factors and possibility theory. AB - Uncertainty management for the evaluation of evidence based on linguistic and conceptual data is taking advantage of developments in the Dempster-Shafer (DS) theory of evidence, possibility theory and fuzzy logic. The DS theory offers the capability to assess the uncertainty of different subsets of assertions in a domain and the way in which uncertainty is affected by accumulating evidence. The DS theory goes beyond probability theory in its ability to represent ignorance about certain aspects of a situation. However, the theory is very sensitive to the numerical assessments provided by users and can lead to intuitively unexpected and even undesirable results. Certainty factors are widely used in various expert systems. Their definition and updating may follow either a probabilistic model or fuzzy set theoretic concept. PMID- 1418267 TI - Nucleoli and AgNOR proteins in 32 cases of primary breast carcinoma. Spatial pattern of interactions between 50 clinical and histometric criteria. AB - The purpose of this paper is to analyze a method allowing selection of the best morphometric criterion for quantifying AgNOR proteins under conventional observation conditions by light microscopy. We determined 50 parameters for 32 cases of primary breast carcinoma. For each case, three 100-nucleus samples (tumor center and periphery on a Giemsa-stained, 3-microns tumor section, periphery on a silver-stained section) were quantified. Distribution-free multidimensional data analysis was used to explore the geometric significance of the coefficient of correlation. This analysis revealed a clinical message linked with the largest "nucleolar structure" (nucleolus or AgNOR clump) per nucleus on the tumor periphery. Tumor recurrence or death correlated only with the coefficient of variation of the "nucleolar/nuclear" ratio of the greatest clump of AgNORs per nucleus periphery (CVRSa). The prognostic value of CVRSa is independent of that of conventional criteria, such as age, tumor size, Scarff Bloom-Richardson grading and lymph node status. The largest AgNOR clump per nucleus may prove to be a further practical prognostic predictor. PMID- 1418268 TI - Quantitative precision of an automated, fluorescence-based image cytometer. AB - Digital image-based cytometry of clinical specimens labeled with fluorescent, disease-specific markers holds promise for becoming an important diagnostic and prognostic technique because the technique can make a diverse range of quantitative biochemical, morphologic, densitometric and contextual measurements on intact specimens. It has been previously shown by us, using an image cytometer (IC) consisting entirely of commercially available components, that the nuclei of individual cells in slide-supported specimens can be detected automatically using a fluorescent DNA stain and image analysis software. The purpose of this study was to determine the precision of the IC for quantifying the integrated fluorescence intensity and area of fluorescent standard beads and nuclei. Integrated intensities could be quantified to between 2.3% and 3.5% precision using a 40x objective lens and between 1.6% and 2.3% using a 20x objective. The main contribution to this uncertainty was 2% inaccuracy in determining the variations in sensitivity over the imaging area. Areas could be quantified to between 0.91% and 2.1% using a 40x objective and between 2.8% and 3.2% using a 20x objective. Significant quantification errors were introduced if the objects were not in focus or were touching each other. Overall, however, these results demonstrated that image cytometry of fluorescence-stained specimens can yield quantitative results with sufficient precision for determining DNA ploidy distributions and for making other measurements on clinical specimens. PMID- 1418269 TI - Effect of storage time of pleural effusions on immunocytochemical cell surface analysis of tumor cells. AB - To determine how long tumor cells can be stored without losing their immunocytochemical reactivity, five malignant pleural effusions in EDTA-coated tubes were analyzed after different storage times at either 4 degrees C or room temperature. Only minor differences were observed between the cells from the two storage conditions. Though there was a considerable decrease in the number of tumor cells attached to the slides from day 0 to 1, the number of tumor cells was still sufficient to allow their clear detection with the monoclonal antibody HEA 125 even on day 4 of storage in all cases. Therefore, for routine purposes, pleural fluids in EDTA-coated tubes can be stored for at least one day prior to immunocytochemical staining if the cells are gently handled during preparation. Pleural fluid is a richly nutritious medium not only for keeping cells alive but also for preserving their immunoreactivity. PMID- 1418270 TI - Morphometry of nuclei of the normal and malignant prostate in relation to DNA ploidy. AB - Fine needle biopsies from 70 patients with prostate carcinoma and 10 patients with benign hyperplasia were used to study area, variation in size and form factors of the nuclei by image analysis. The results were related to DNA ploidy of the cell populations as measured by flow cytometry, cytologic grade and patients' survival. Nuclear area differed significantly between benign lesions and tumors. It increased in diploid low-grade tumors from a normal value of 54.2 +/- 3.1 microns2 to 75.6 +/- 5.3 microns2. In aneuploid tumors with an increase in the chromosome number, the nuclear size further increased to about twice that of benign nuclei. Variation in size also differed between benign and malignant epithelium, with a further increase between diploid and gross aneuploid tumors. While nuclear size and variation in nuclear size made it possible to discriminate malignant from benign lesions, form factor did not differ between benign and malignant lesions. In follow-up, however, none of these factors reached significance for predicting survival. PMID- 1418271 TI - Prognostic importance of the DNA ploidy pattern in malignant mesothelioma of the pleura. AB - Malignant mesotheliomas often raise a difficult diagnostic problem: once the diagnosis is made, the possibilities of predicting the biologic activity and prognosis of the tumor are limited. DNA ploidy patterns have been used as a prognostic instrument for other tumors, and this pattern was therefore studied in 37 cases of verified mesothelioma. The measurements were made on Feulgen-stained smears from pleural effusions using a Leica Miamed computer microscope. When a highly aneuploid tumor was defined as a condition with greater than 5% of the cells within defined intervals outside the ranges of the stem-line and the peaks representing polyploidization thereof, a near-diploid/polyploid pattern was obtained in 41% of the cases, while the remaining 59% were classified as highly aneuploid. The prognosis was significantly better among the near diploid/polyploid cases. This estimate of the outcome could not be improved by using alternative algorithms for high-grade aneuploidy. PMID- 1418272 TI - DNA analysis of malignant effusions. Comparison with cytologic diagnosis and carcinoembryonic antigen content. AB - Twenty-three consecutive malignant effusions from 19 patients submitted for cytologic examination were analyzed for carcinoembryonic antigen (CEA) content and for DNA analysis by flow cytometry. The study was undertaken to determine if the addition of DNA analysis would improve the sensitivity of cytologic diagnosis and CEA assay. CEA examination was performed on Papanicolaou-stained smears and hematoxylin-and-eosin-stained cell blocks. Final diagnoses were correlated with histologic examination (four patients), clinical and radiologic studies, and follow-up. The malignant effusions in 19 patients were secondary to carcinoma of the breast (5), lung (5), ovary (1), endometrium (1), mucinous carcinoma of the colon (1), unknown primary (1), extraovarian papillary carcinoma (1), mesothelioma (2) and large cell lymphoma (2). The sensitivity of cytologic diagnosis was 100% and specificity 100%. DNA aneuploidy, defined as the presence of two separate peaks in the histogram, was present in 7 of 23 fluids (sensitivity, 30%). Four fluids had insufficient cells for analysis, and one histogram showed debris (following chemotherapy). DNA aneuploidy was detected in effusions secondary to carcinoma of the breast (4), lung (1) and lymphoma (2). Using 5 ng/mL as the cutoff, the sensitivity of CEA was 68%. DNA analysis of cells in malignant effusions is less sensitive than cytologic diagnosis, and CEA assay and is not recommended for routine use in the diagnosis of malignant effusions. PMID- 1418274 TI - Information, discrimination and divergence in cytology. V. General symmetry of total discrimination and total divergence. AB - Total discrimination and divergence are derived from Baye's theorem and based on backward (a posteriori) probabilities. Total forward (a priori) discrimination and divergence can be computed from a test matrix from which total backward discrimination and divergence were calculated for optimization of the classifications of gynecologic cytology (Papanicolaou smears) and quality control in a laboratory. The total forward discrimination and divergence appears to behave in parallel with the total backward discrimination and divergence, and the discrepancies in the backward and forward discrimination/divergence were the smallest near the optimum classification scheme. Conversely, the discrepancies between backward and forward discrimination and divergence may be helpful in finding the best classification scheme for gynecologic cytology. The general symmetries of the total backward and forward discrimination/divergence may be related to the human cognitive process of preferring symmetry and to the historic process in which cytologic classification followed histologic classification and continuously checked for matches in two directions--i.e., from histology to cytology and vice versa--thus resulting in the preservation of symmetry. PMID- 1418273 TI - The three-group metaphase as a morphologic indicator of high-ploidy cells in cervical intraepithelial neoplasia. AB - There is a need for additional morphologic criteria to improve the value of histologic classification for the prediction of the biologic behavior of cervical intraepithelial neoplasia (CIN). Representative slides from 72 cone specimens containing CIN were examined to study the correlation between the presence of three group metaphases (TGMs), a morphologically well defined and light microscopically readily recognizable atypical mitotic figure, and the incidence of aneuploid cells with a nuclear DNA content greater than 5C. The numbers of cells greater than 5C (minus the polyploid cells 8C +/- 1C) were counted, using LEYTAS image cytometry on Cytospin preparations from the 72 blocks corresponding to the slides searched for TGMs and used for histologic classification of the lesions in classes CIN 1-3. It appeared that large numbers of aneuploid cells greater than 5C were more closely related to the presence of TGM than to a higher CIN class per se, particularly in women older than 35. Since aneuploid CIN has a higher progression rate than euploid CIN, the presence of TGMs will indicate a biologically unfavorable lesion. Thus, TGM deserves further investigation as an additional morphologic parameter for predicting the biologic behavior of CIN. PMID- 1418275 TI - Information, discrimination and divergence in cytology. VI. Biases and errors of measurement in small samples. AB - Total discrimination and total divergence have been shown to be useful measures of performance in diagnostic cytology. The sample size, Ns (observed number of cytology-histology pairs, essential components of a confusion matrix), may be small for the comparison of two or more laboratories or periodic quality control using observed values. From actual data from previous reports in this series, the best estimation of the confusion matrix of a population was obtained by fitting a Gaussian-type curve after pseudoscalar transform of ranks (row and column numbers). Small sample confusion matrices were generated by Monte Carlo simulation to 2.5 x 10(-7) resolution. To keep measurement biases within +/- 0.5 decits, we found that 100-200 samples of cytology-histology pairs were required in the best classifications of three, four and five category-states. At these sample sizes, measurement errors (standard errors) were also contained within +/- 0.5 decits. This study also confirmed that previously reported overestimated propagated errors in small samples were in fact overestimation and that their use for testing a null hypothesis was valid. The number of samples with indefinable statistics due to a zero denominator can be as high as 30% when the sample sizes are 500 for three, four and five category-state classifications. Biases due to small samples were positive for most category-states except for the optimum three category-states, in which bias changed to negative ("bias inversion"), and observed errors of discrimination and divergence paradoxically decreased as Ns decreased ("error-sample paradox") for a small sample size (Ns less than 700).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418276 TI - [Atropine versus glycopyrrolate in eye surgery. A comparison of rhythm disorders and heart frequency using Holter-ECG]. AB - Anticholinergics are indicated in ophthalmic surgery to inhibit oculocardiac reflexes (OCR). Although all anticholinergics exert an arrhythmic effect, comparative data on occurrence and severity of arrhythmias are not available. The aim of this investigation was to compare atropine (A) and glycopyrrolate (G) in adults undergoing ophthalmic surgery. One hundred patients (ASA class I and II, age range 20-60 yrs.) were given equipotent doses of either A (10 micrograms.kg 1) or G (5 micrograms.kg-1) in a randomized, double-blind fashion, before induction of anaesthesia. Continuous Holter monitoring was performed. The procedure was divided into the following phases: O (5 min before drug), I (5 min after drug), II (up to induction), III (induction until intubation), IV (intubation until operation), V (operation). Supraventricular, junctional, and ventricular arrhythmias were analyzed. Severe arrhythmia was judged to be greater than 5 events per min, or ventricular beats Lown classes III-V. The beat to beat analog signal was digitalized. The heart rate (HR) and the occurrence rate of OCR (greater than 20% decrease in heart rate, arrhythmias) was calculated by a computerized program. Analysed were: 1. the frequency of OCR, 2. the mean HR for each phase, 3. the frequency of all the various arrhythmias during the whole period, 4. as well as for each phase. The number of patients with severe arrhythmias 5. either for all the time or 6. for the individual phase were registered separately. There were no differences 1. in the frequency of OCR and 2. in mean HR during all phases between A and G.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418277 TI - [The effect of etomidate on the upper airway reflexes]. AB - Clinical observations during anaesthesia and intubation of emergency patients are presented showing a differentiated impact of etomidate (Hypnomidate) on upper airway reflexes: a blockade of pharyngeal reflexes with sustained but possibly delayed laryngeal reflexes and a certain protection against laryngospasm and vomiting. In addition etomidate enables, preferably in combination, difficult intubation with sustained spontaneous breathing due to its low respiratory depressant effect. These features were confirmed in a small foreshortened clinical study using thiopentone (Trapanal) or etomidate without muscle relaxants, whereby the difference in high risk patients became obvious. The impact of anaesthetics on airway reflexes is generally concealed by muscular relaxants, and observations on this matter are difficult to make subject to quantifiable parameters and controlled studies; accordingly such observations are scarcely found in newer anaesthetic literature. In the development of new techniques for intubation and anaesthesia without muscle relaxation, these methodical problems deserve attention. PMID- 1418278 TI - [Propofol for sedation during postoperative mechanical ventilation. A comparative study with Lytic Mixture]. AB - Propofol infusion was found to provide excellent sedation and rapid recovery in intensive care. The present study compared Propofol with lytic solution (lytic solution = mixture of 100 mg Pethidine, 50 mg Promethazine and 0.6 mg Dihydroergotamine) during 6 hours of postoperative artificial ventilation. 60 patients after major abdominal surgical procedures were studied with ethical committee approval and informed consent. Patients were randomly allocated to receive either Propofol or lytic solution. We aimed at a sedation level of stage 5 according to the Ramsey score. The mean drug dosages were 3.9 mg/kg/h of Propofol and 4.2 ml/h of lytic solution. Hemodynamic values, blood gases as well as various biochemical measures did not show any difference between the groups. At the end of the sedation period triglyceride concentrations were significantly higher in patients receiving Propofol (166 + 79 mg/dl) compared to the control group (97 + 60 mg/dl). Significant and relevant differences were found for the times of recovery after discontinuation of the sedative. These times were very short in the Propofol group. Furthermore, in view of a longer recovery time after lytic solution in this group the respiratory rate was significantly slower up to the end of the observation period. We conclude that a major advantage of Propofol in the present study was the rapid recovery after 6 hour sedation. Patients gain vigilance rapidly and sufficient spontaneous respiration within minutes. Not at least thanks to these facts patient's safety can be improved in the recovery period. PMID- 1418279 TI - [Death and assisted death--current medical, ethical and legal questions]. AB - Taking care of dying people is one of the most difficult obligations of the physician, perhaps the most difficult one. In this field, a lot of ethical problems arise which have to be coped with. In German the term "Sterbehilfe" ("helping to die") has more and more replaced the medical term "euthanasia". At present there are doubts whether this new term "helping to die" is useful because it might reflect liberal attitudes towards human life. Due to this terminological uncertainty many physicians are in two minds about the way of taking care of dying patients. Using an exact and unequivocal term for dying without pain and torture is an important demand for modern medicine in order to increase people's confidence in the last stage of their lives. PMID- 1418281 TI - [The humidification of anesthetic gases during anesthesia using heat and moisture exchangers]. AB - This study looks at the question of whether anaesthetic gases are sufficiently moistened in a semi-closed system by the partial recycling of expired air with simultaneous absorption of CO2. During the inspiration phase only a maximum of 42% relative humidity at a temperature of 24.8 degrees C was reached. These values lie far below the demands of the American National Standard Institute (ANSI) of 70% relative humidity at 30 degrees C. When various heat and moisture exchangers were used, the relative humidity improved to 99% at a maximum temperature of 30.3 degrees C (HME Edith; Engstrom Corporation). The maximum values of the BB 12-15, Pall Corporation, and SH 150 from Siemens were slightly lower. A marked fall was noticed when using the Humid Vent I of the Medimex Corporation, especially in the initial phase. An improved version, the Humid Vent II, has been produced. Physiological values (37 degrees C, 100% relative humidity) are not achieved by any heat and moisture exchangers. This problem could possibly be solved by using infra-red light when warming the gases. PMID- 1418280 TI - [The treatment of status asthmaticus using ketamine--experimental results and clinical experience]. AB - Intensive therapy of a patient with status asthmaticus must lead to a reduction of vital threat by improving respiratory and cardiac functions. Because of the bronchodilating effect of ketamine, analgesic sedation with ketamine and benzodiazepines is extremely useful for prolonged ventilation. At the beginning of this treatment it can be necessary to supplement the continuous intravenous infusion of ketamine and diazepam or ketamine and midazolam with small bolus doses of up to 3.5 mg/kg/h of ketamine. Experience has shown that the combination of ketamine and midazolam has better controllability. In some of our patients the bronchodilating effect of ketamine was not sufficient and therefore ventilation with halothane was necessary at least intermittently. In contrast to halothane, ketamine can be combined with vasodilators and sympathomimetics as our own experience has shown. The combined application of ketamine with glycerol trinitrate or sodium nitroprusside is indicated in the event of pulmonary or general hypertension. The use of sympathomimetics--mainly beta-sympathomimetics- antagonizes the negative inotropic effect of ketamine, improves the circulatory system and leads to a direct bronchodilating effect. Progress in treatment was mainly achieved by continuous intravenous infusions of terbutaline (Bricanyl). Aminophylline is very compatible with ketamine, but because of its stimulating effect the use of aminophylline seems to be reasonable only during weaning from the ventilator. Control of the usually deep analgesic sedation and an accompanying optimum drug therapy are only possible with complete cardiorespiratory monitoring including invasive blood pressure measurement and catheterization of the pulmonary artery. In our clinic 24 patients with status asthmaticus were treated. Sixteen asthmatic patients were treated with analgesic sedation using ketamine and benzodiazepines, three of them without intubation and ventilation. In spite of the life-threatening situation and reanimation before admission to the intensive care unit, only one patient died. Our experience has shown that intensive therapy including analgesic sedation with ketamine and benzodiazepines, optimized by application of sympathomimetics and vasodilators, is suitable for overcoming the life-threatening situation of patients with status asthmaticus. PMID- 1418283 TI - ET nurses expanding our practice. Behavioral interventions for incontinence. PMID- 1418282 TI - [The HELLP syndrome--a challenge to the obstetrician and the intensive care therapist]. AB - The HELLP-syndrome is a severe complication in late pregnancy. The etiology is still largely unknown. It is defined as a separate disease but also as a severe course of EHP-gestosis. It is mainly characterised by increased liver enzymes, a low platelet count, increased haemolysis and hypertension. According to primary organ affection, neurological symptoms and acute respiratory distress syndrome, acute renal insufficiency and/or upper abdominal complaints may occur. The only causal therapy is immediate caesarean section. Postoperative intensive care must be guaranteed. As a gentle anaesthetic method neuroleptanalgesia is recommended. Based on 7 of our own case reports, pathophysiology and therapy are discussed. PMID- 1418284 TI - Product notebook: occlusive skin paste. AB - When selecting products for the prevention or treatment of skin breakdown due to fecal incontinence and diarrhea, the health care professional should consider the following: ETIOLOGY: The premixed skin paste we tested, Critic-Aid, is an important part of our treatment plan, but it is not a cure for the etiology of loose stools. SAFETY: Use premixed products, or ingredients in an institutional mixture, only in ways approved by the FDA. Convenience: The staffing situation has made the use of time-savers imperative. Quality Control: The product you use or mix should perform consistently. Cost: Choose the most cost-effective product that meets your patients' needs. Conventional treatments and preparations failed to prevent or heal skin breakdown in our patients with fecal incontinence and diarrhea. In response to this problem, we concocted our own institutional mixture, using only ingredients approved by the FDA for use in wounds and consulting the hospital pharmacist at every turn. However, the procedural and potency problems resulting from our institutional mixture prompted us to test a premixed skin paste, Critic-Aid, which exceeded our expectations. PMID- 1418285 TI - Clean intermittent catheterization. PMID- 1418286 TI - A study of wound healing in home care. PMID- 1418287 TI - A lifetime of incontinence. PMID- 1418288 TI - Antibodies to mycobacterial 65 kDa heat shock protein in systemic sclerosis (scleroderma). AB - It has been reported that immunity to the 65 kDa heat shock protein of Mycobacterium tuberculosis (MT-hsp65) not only accompanies rheumatoid arthritis (RA), but may also be characteristic of chronic inflammation. We now report serum antibodies to MT-hsp65 in 47% of systemic sclerosis (SSc), 38% of primary Raynaud's phenomenon (PRP) and 5% of systemic lupus erythematosus (SLE). Antibody levels were higher in patients with active or progressive SSc and correlated with the degree of skin fibrosis. Thus, immunity to MT-hsp65 appears in SSc and is not limited to RA. However, it does show some degree of specificity beyond chronic inflammation: PRP patients have a higher reactivity than do SLE patients. PMID- 1418289 TI - Secretory granule autoantigen in insulin-dependent diabetes mellitus is related to 62 kDa heat-shock protein (hsp60). AB - Recent studies in NOD mice suggest that cellular and humoral responses against beta cell protein(s) cross-reactive with mycobacterial heat-shock protein, hsp60, are implicated in the development of autoimmune diabetes. However, this putative, hsp60-related autoantigen has not yet been identified nor have the preceding events triggering the autoimmunity against it. Our recent studies show that antibodies to the mammalian hsp60 bind specifically to the 62 kDa protein located to insulin secretory granules and mitochondria of pancreatic beta cells of healthy mice [1]. In islets of prediabetic NOD mice affected by insulitis, the cellular distribution of this hsp60-related antigen was found to be altered. In the present report, we have examined whether this endogenous hsp60-related protein of secretory granules serves as an autoantigen in type I diabetes. The results of Western blot analysis indicate that diabetic mice sera show reactivity to a 62 kDa islet cell antigen. The NOD mice sera that were positive in detection of the 62 kDa islet cell antigen were also able to recognize the recombinant human hsp60. Immunogold electron microscopy revealed that diabetic NOD mouse sera, cross-reactive to human recombinant hsp60, recognize the antigen located in secretory granules of beta cells. Double-immunogold labelling demonstrated that antigens recognized by both diabetic NOD mice sera and monoclonal hsp60 antibodies co-localized in the same secretory granules of beta cells. Preincubation of islet cell sections with one type of antibody blocks subsequent binding of the other, indicating that epitopes recognized by both antisera on these proteins are shared. Moreover, preadsorption of diabetic sera with the recombinant human hsp60 abolished labelling of secretory granules. These results indicate that the hsp60-related protein of beta cell secretory granules is an autoantigen in type I diabetes in NOD mice. PMID- 1418290 TI - Induction of experimental anti-phospholipid syndrome associated with SLE following immunization with human monoclonal pathogenic anti-DNA idiotype. AB - MIV-7 is a human monoclonal antibody that binds to DNA and carries a pathogenic anti-DNA idiotype 16/6. The antibody was generated by fusing peripheral blood lymphocytes of a healthy donor which were stimulated with an anti-idiotypic antibody to B11 (a human mAb anti-mouse mammary tumor virus-MMTV). The MIV-7, in addition to being an anti-DNA antibody, also binds to MMTV glycoproteins. Following immunization into the footpad of naive BALB/c mice with MIV-7, the mice developed anti-phospholipid syndrome (APLS) and SLE. The APLS was characterized by thrombocytopenia, the presence of anticardiolipin antibodies, lupus anticoagulant (prolonged APTT), high resorption rate of fetuses and lower mean weights of the placentae and fetuses. The SLE was characterized by serological markers (e.g. anti-DNA), laboratory (increased sedimentation rate and proteinuria) and histological findings (deposition of immune complexes in the glomeruli). Active immunization of mice with mouse monoclonal anti-cardiolipin antibodies led to the induction of primary APLS without SLE. The results add to our previous passive transfer model in which mouse monoclonal anti-cardiolipin antibody generated from immunized mice (CAM) was infused into the tail vein and also resulted in induction of pure APLS [11]. Our results demonstrate the ability to induce secondary APLS to SLE following immunization with a pathogenic idiotype of anti-DNA antibodies and to induce primary APLS with anti-cardiolipin mAb. The existence of these experimental models may permit controlled studies of novel therapeutic models. PMID- 1418291 TI - Production and characterization of human hybridoma monoclonal anti-Sm and anti U1RNP antibodies spontaneously produced from normal human lymphocytes. AB - A panel of human:human hybridomas secreting monoclonal anti-Sm/RNP antibodies was established by the fusion of normal human tonsillar lymphocytes to the lymphoblastoid B cell line GM4672. The specificity of these antibodies was studied by direct binding and competitive inhibition in enzyme linked immunosorbent assays (ELISAs), and by immunoblotting. The stable subclones of these hybridoma monoclonal anti-Sm/RNP antibodies could be classified into four groups according to ELISA. Group I bound Sm/RNP only, group II bound Sm-RNP, Ro/SS-A and La/SS-B, group III bound Sm/RNP and ssDNA, and group IV bound Sm/RNP, Ro/SS-A, La/SS-B and ssDNA. When antibodies from each of the groups were tested by immunoblotting, the following pattern of reactivity emerged. Group II and IV antibodies reacted with U1RNP-A, Sm-B'/B, Sm-D and Sm-E proteins, as well as the Ro/SS-A and La/SS-B proteins. In contrast, group I and III antibodies did not bind to any individual protein components of Sm/RNP,Ro/SS-A or La/SS-B antigens, but recognized their conformational epitopes. These results, therefore, directly demonstrate for the first time that normal-derived B cells have the genetic potential, revealed here by somatic cell hybridization, to produce anti-Sm/RNP antibody responses which are ordinarily only associated with systemic lupus erythematosus (SLE) and related connective tissue diseases. PMID- 1418292 TI - Thymulin and its role in immunomodulation. AB - Even though thymulin was isolated, sequenced and characterised some 20 years ago and later identified as a thymic hormone involved in immunomodulation, much more work is still required to further understanding of the mechanisms of action(s) of this peptide. Since the observation, by a semiquantitative bioassay, of diminished levels of thymulin in immunodeficiency and autoimmune disease, new data obtained by radioimmunoassay have not only confirmed previous observations but also demonstrated that thymulin plays a role in the interaction between the immune system and the neuro-endocrine system. In this paper we give an up to date account of recent developments in research into the role of thymulin in immunomodulation. PMID- 1418293 TI - Analysis of anti-idiotypic antibodies against anti-microsomal antibodies in patients with thyroid autoimmunity. AB - Anti-microsomal antibody (AMA) activity was inhibited in 14 of 16 sera and in all 12 IgG preparations from patients with postpartum thyroiditis following incubation with F(ab')2 fragments from normal polyspecific immunoglobulin for therapeutic use (ivIg). Similar results were observed with sera from seven of seven patients with Graves' disease and five of six patients with autoimmune hypothyroidism. Results of these competitive binding assays and affinity chromatography of AMA IgG on Sepharose-bound F(ab'), fragments from ivIg indicated that AMA antibodies reacted with ivIg through idiotypic-anti-idiotypic interactions. Eight out of 10 IgG preparations from patients with autoimmune thyroid disease also showed inhibition of AMA activity when coincubated with autologous IgM at various IgG:IgM molar ratios. These observations suggest that ivIg can inhibit anti-microsomal antibodies through idiotype-anti-idiotype interactions and that such interactions occur with IgM anti-idiotype antibodies in vivo, providing evidence of a role for idiotypic network regulation in the control of thyroid autoimmunity. PMID- 1418294 TI - Involvement of dendritic cells in early insulitis of BB rats. AB - In this study, subsets of mononuclear infiltrates in pancreatic islets of BB rats at different stages of insulitis were determined by various monoclonal antibodies against rat lymphoid cells, including a mouse monoclonal IgM antibody that distinguishes between macrophages and dendritic cells (mAb 1F119). 1F119+ dendritic cells were absent in and around islets of Wistar control rats. In BB rats, the first alteration of islets detectable by immunohistochemistry when compared with normal islets was the enhanced expression of 1F119 antigen around and in the islets (17% 1F119+ islets). At disease stage 1 (i.e. no leukocyte infiltration after HE staining), lymphocytes and macrophages were almost absent. At disease stage 2 (leukocyte infiltration < 20 cells), a more intense form of dendritic cell infiltration was seen (stage 1 versus stage 2, P < 0.0001). In addition, ED2+ and ED3+ cells were present around the islets (50% of islets were infiltrated with 1F119+ cells versus 16% with ED2+, 19% with ED3+, 11% with W3/25+ cells, and 11% with OX8+ cells, P < 0.0001). At disease stage 3 (> 20 cells), a clear increase of ED2+ and ED3+ macrophages and of W3/25+ and OX8+ T lymphocytes in the infiltrates was observed. These observations suggest a role for antigen presenting dendritic cells in the initiation of immune reaction in type 1 diabetes of BB rats. PMID- 1418295 TI - Incidence and phenotype restriction of lymphoid BLT-serine protease granules in spontaneously diabetes prone BB rats compared with a normal rat strain. AB - In diabetes prone BB rats a relative increase of serine protease (SP)-positive lymphocytes (39.8 +/- 10%) was observed in peripheral blood at the time of diabetes manifestation (DM) compared with non-diabetic healthy Sprague Dawley control rats (Co: 10.3 +/- 4%), with BB rats at age of premanifestation (PM: 14.7 +/- 4%) and beyond age of expected manifestation (non-diabetic animals, ND: 25.2 +/- 4%). Similar absolute numbers were found in diabetic BB rats in comparison with Sprague Dawley rats. In PM, absolute numbers were lower in comparison with diabetic BB rats. SP granular positivity was found restricted to OX8+ lymphocytes. SP granule-bearing OX8+ lymphocytes were more frequently seen in the BB rat strain (PM: 74.3 +/- 8%; DM: 79.4 +/- 8%; ND: 78 +/- 10%) compared with normal rats (Co: 32.5 +/- 8%). Absolute numbers were lower in PM animals in comparison with DM rats. OX8+ cells were found in a higher relative number in DM animals (49.1 +/- 7%) compared with controls (28.2 +/- 3%), PM (26.3 +/- 5%) and ND (34 +/- 2%) animals. T lymphocytes expressing the W3/25+ marker, invariably negative for SP granules, were present in a higher relative number in ND (49.8 +/ 7%) and the control group (52.3 +/- 10%) compared with PM (31 +/- 8%) and DM (38 +/- 11%) animals. Absolute numbers of the OX39+ lymphocyte subpopulation were decreased in PM and DM-BB rats in comparison with the control group. PMID- 1418296 TI - Acquired allo-tolerance to major or minor histocompatibility antigens indifferently contributes to preventing diabetes development in non-obese diabetic (NOD) mice. AB - Diabetes in NOD mice represents the end stage of a genetically-programmed autoimmune process mediated by T lymphocytes and directed against insulin producing beta cells. We have shown in a previous study that the course of the disease is significantly inhibited in NOD mice which have been made tolerant at birth to foreign histocompatibility antigens. This early T cell manipulation results in a significant delay of disease onset, reduced overall incidence and less severe alterations of islet cells. In order to characterize better the nature of the foreign tolerogenic determinants responsible for this protection, we have now examined separately the contribution of MHC and non-MHC antigens. Two lines of congenic mice were used as donors of tolerogenic cells, NOD.H-2b, which differ from NOD by the MHC-encoded antigens only, and B10.H-2g7, which differ by all the minor histocompatibility antigens encoded by the B10 background, but which share with NOD mice the same MHC haplotype. Our results show that NOD recipients of F1 semi-compatible cells become specifically tolerant to the set of alloantigens to which they were neonatally exposed. Unresponsiveness, assessed by lack of CTL generation, is profound and specific. Yet, despite the fact that distinct sets of alloreactive T cell precursors are silenced, mice made tolerant indifferently to major or minor histocompatibility antigens are significantly protected against overt diabetes. These results could mean that each set of MHC and non-MHC encoded determinants can independently cross-tolerize a sufficient proportion of the autoreactive repertoire to slow the natural course of the disease. Alternatively, neonatally-acquired tolerance might induce polyclonal activation of the immune system resulting in the suppression or the immunodeviation of potentially harmful, autoreactive T cell clones. PMID- 1418297 TI - Cultured fibroblasts in avian scleroderma, an autoimmune fibrotic disease, display an activated phenotype. AB - University of California, Davis, line 200 and 206 chickens spontaneously develop an autoimmune syndrome that has many features analogous to human scleroderma, including dermal fibrosis, antinuclear antibodies and antibodies to type II collagen. These birds also have thymic subcapsular epithelial defects and an abnormality in T cell calcium influx and proliferation in response to both T cell receptor-dependent and -independent activators. To determine whether fibroblast activation is a contributing factor to development of skin fibrosis in line 200/206 chickens, as it is in human scleroderma, we studied the collagen, non collagenous protein and glycosaminoglycan (GAG) production of 34 separate fibroblast lines derived from the normal and fibrotic skin of line 200 and 206 chickens and from the skin of control chicken lines 058 and 254. The mean +/- SEM 24-h incorporation of 3H-proline or 3H-glucosamine into extracellular collagen, non-collagenous protein or GAG by first passage fibroblast lines derived from the fibrotic skin of diseased birds was 1,526 +/- 136, 859 +/- 82 and 25.7 +/- 1.3 dpm/10(3) cells, respectively, while fibroblast lines derived from the skin of control birds produced only 341 +/- 36, 343 +/- 42 and 15.2 +/- 1.4 dpm/10(3) cells. Similar differences in results were recorded for cell-associated production, and when collagen and non-collagenous protein production were assessed using non-radioactive electrophoretic methods. The activated phenotype of the fibroblast lines derived from the fibrotic skin of diseased birds persisted through 10 cell doublings in tissue culture. However, the ratio of type I:III collagen and the profile of GAG types produced were similar in all fibroblast lines studied. These results suggest that fibroblast activation is responsible for the skin fibrosis observed in this avian model of scleroderma. PMID- 1418298 TI - Autoimmune thyroiditis (EAT) in genetically resistant mice mediated by a T cell line. AB - Experimental autoimmune thyroiditis (EAT) can be induced in genetically susceptible strains of mice by immunization to mouse thyroglobulin (Tg). EAT also can be produced by administration of anti-mouse Tg T cell lines and clones. Previously we were able to raise virulent anti-Tg T cell lines from mice genetically susceptible to EAT. These virulent lines, upon attenuation, were able to vaccinate the susceptible mice against EAT. We now report the isolation of a virulent T cell line from C57BL/6 mice genetically resistant to EAT. The T cell line and its clones recognize a Tg epitope cross-reactive between mouse and bovine Tg. Unexpectedly, the virulent anti-Tg line attenuated in various ways failed to vaccinate C57BL/6 mice against EAT mediated by the line itself. These results shed some light on the regulation of autoimmunity. PMID- 1418299 TI - Susceptibility and resistance to autoimmunity following neonatal injection of semi-allogeneic spleen cells in rats. AB - A model of neonatal allotolerance was developed in rats. Brown-Norway (BN) neonates injected with semi-allogeneic (BN x Lewis) F1 hybrid spleen cells express a long-lasting chimerism and exhibit polyclonal B cell activation demonstrated by hyperimmunoglobulinemia affecting mainly IgE and IgG1, anti laminin and anti-DNA autoantibodies as well as glomerulonephritis and anti-hapten antibodies. These abnormalities are autoregulated although the chimerism persists. In contrast, Lewis (LEW) neonates injected with semi-allogeneic (BN x LEW) F1 hybrid spleen cells exhibit a very short-lasting chimerism and transient activation of B cells, as reflected by increased allo-class II antigen expression, but do not develop an autoimmune disease. The autoimmune syndrome observed in BN rats is similar to that reported in mice during host-versus-graft reaction. Similarities between the drug-induced models of autoimmunity and allogeneic reactions in BN rats are also striking. The susceptibility of BN rats and the resistance of LEW rats to these autoimmune diseases might respectively reflect the involvement of TH2-like or of TH1-like subsets. PMID- 1418300 TI - Acquisition of autoimmunity genes by New Zealand mice is associated with natural resistance to infection by mycobacteria. AB - New Zealand (NZ) mouse strains comprise both autoimmune and non-autoimmune animals: NZ black (NZB) mice and the F1 hybrid (NZB/W) of NZB and NZ white (NZW) mice show spontaneous autoimmune disease by 6 months of age and die before the first year of age from renal disease, while NZW mice do not show autoimmune disorders. We investigated whether the autoimmunity-prone NZ animals (NZB and NZB/W) differ from the non-autoimmune NZW mice in susceptibility/resistance to mycobacterial infection. The three groups of NZ mice were infected by intraperitoneal inoculation of 10(8) colony forming units (cfu) of Mycobacterium avium. The M. avium infection was induced in 3-month-old mice (i.e., before NZB and NZB/W mice develop autoimmune disease) and studied for 4 months. Infected NZB and NZB/W mice showed evidence of renal disease at 2 and 4 months of infection (but not at 1 month). The non-autoimmune NZW mice were found to be susceptible to M. avium since they allowed massive proliferation (4-5 log growth) of the bacilli in liver and spleen. In contrast, both groups of autoimmunity-prone mice (NZB and NZB/W) were resistant to M. avium since their mycobacterial loads remained below the value of the initial inoculum. We conclude that in NZ mice the acquisition of autoimmunity genes is associated with expression of natural resistance to mycobacterial infection. This is consistent with the view that autoimmunity genes may have been evolutionarily selected because of their association with increased resistance of the host to infections by intracellular parasites. PMID- 1418301 TI - Induction of anti-DNA IgG and IgE antibodies in BALB/c mice. AB - Immunization of BALB/c mice with denatured DNA (dnDNA)-methylated bovine serum albumin (MBSA) complex along with aluminium hydroxide gel as adjuvant, resulted in the induction of anti-DNA antibodies of both IgG and IgE isotypes demonstrable by avidin-biotin micro enzyme-linked immunosorbent assay (ELISA) and solid phase radioimmunoassay (SPRIA), respectively. In contrast to the high levels of IgG2a and IgG2b anti-DNA antibodies observed in SLE-prone autoimmune mice, more than 90% of the anti-DNA antibodies of IgG isotype were found to be of IgG1 subclass. Specificity of both IgG and IgE antibodies which recognized activated DNA, dnDNA and double-stranded DNA but not RNA was established by competitive ELISA and SPRIA inhibition assays. These antibodies cross-reacted with cibacron blue and chondroitin sulfate but not with various other proteoglycans, nucleosides and nucleotides. Passive cutaneous anaphylaxis reaction in rats showed that these antibodies are capable of inducing in vivo degranulation of mast cells in a dose dependent manner. These studies lend support to the concept that IgE antibodies directed against DNA may mediate mast cell degranulation and thus contribute to immediate-type hypersensitivity phenomena including hives seen in patients with systemic lupus erythematosus and to the localization of IgE-nucleic acid complexes. PMID- 1418303 TI - Continuous cocaine induces persisting changes in behavioral responsivity to both scopolamine and diazepam. AB - Forty-eight male rats were administered continuous cocaine, daily cocaine injections (intermittent), continuous amphetamine, or no drug for 5 days. Beginning 45 days after the administration all groups were tested for their responsivity, as measured by automated activity cages, to a low dose of the cholinergic agonist scopolamine. The continuous cocaine group showed decreased sensitivity to this challenge as compared to the other groups. When tested with a low dose of diazepam, the continuous cocaine group showed the greatest response. However, when observed following an injection of cocaine HCl, the intermittent cocaine group showed the greatest behavioral response. These findings support those of previous studies that indicated that the mode of initial cocaine administration is a key factor in the production of persisting changes in behavior and biochemistry. PMID- 1418302 TI - Forebrain norepinephrine: role in controlled information processing in the rat. AB - A series of experiments examined the effects of 6-hydroxydopamine (6-OHDA) induced depletion of forebrain norepinephrine (NE) on the performance of a visual detection (spatial localization) task. The behavioral paradigm used was an analogue of Leonard's 5-choice serial reaction time task for humans. The 6-OHDA lesion of the dorsal noradrenergic bundle (DNAB) produced a 98% depletion of the NE content in the neocortex, and a much smaller depletion (32%) of the NE content in the hypothalamus. As reported previously, performance of visual discrimination was unaffected by DNAB lesions, even when the discrimination was made more difficult by decreasing the intensity of the visual stimuli. However, the lesion produced a significant decrease in accuracy and a significant increase in omissions when a burst of loud white noise was presented just prior to the onset of the visual discriminanda. Similarly, a significant decrease in discriminative accuracy was produced in the rats with forebrain NE depletion by systemic administration of the psychomotor stimulant, d-amphetamine (0.2 to 0.8 mg/kg). In both of these experiments, the lesion-induced discrimination impairment was not magnified by reducing the brightness of the visual discriminanda, suggesting that the behavioral impairment was not caused by a decreased ability to detect the visual stimuli. In addition, the lesion impaired discriminative accuracy when the visual discriminanda were presented at an unpredictable rate. The implications of these behavioral impairments produced by forebrain NE depletion for theories of catecholamine involvement in attentional processes and arousal are discussed in terms of a possible role for the DNAB in controlled or "effortful" processing. PMID- 1418304 TI - Circadian changes in psychologic effects of ethanol. AB - Six healthy human males (aged 22 to 26 years) synchronized with diurnal activity from 0700 hours to midnight and nocturnal rest, volunteered to document changes in psychologic variables resulting from ethylalcohol ingestion (ethanol 0.67 g/kg of body weight). For each subject four separate tests were performed at least 1 week apart at 0700, 1100, 1900, and 2300 hours in randomized order, with measurements taken before and 15, 30, 60, 90, 120, 140 minutes postingestion and thereafter at 4-hour intervals during a 24- to 36-hour period. Subjects fasted for 12 hours preceding ethanol ingestion time and for 8 hours thereafter. Self rated inebreity (visual analogue scale) was greatest after ingestion at 2300 hours and lowest after ingestion at 1100 hours. Both speed to perform random number addition and eye-hand skill tests were slowest after ingestion at 2300 hours. However, changes observed for self-rated physical vigor, tempo, hand-grip strength, and systolic blood pressure did not appear to be ethanol ingestion time dependent. Validated ethanol ingestion time-dependent effects including those of oral temperature were not related to changes in the drug pharmacokinetics. PMID- 1418305 TI - Selection and utilization of outcome measures in psychiatric clinical trials. Report on the 1988 MacArthur Foundation Network I Methodology Institute. PMID- 1418306 TI - Pharmacologic evaluation of SCH-39166, A-69024, NO-0756, and SCH-23390 in neonatal-6-OHDA-lesioned rats. Further evidence that self-mutilatory behavior induced by L-dopa is related to D1 dopamine receptors. AB - The purpose of the present investigation was to explore further the hypothesis that the self-injurious behavior induced by L-dihydroxyphenylalanine (L-DOPA) in neonatal-6-hydroxydopamine (OHDA)-lesioned rats is associated with an action on D1 dopamine receptors. This was accomplished by examining the behavioral responses induced by SKF-38393, quinpirole, and L-DOPA after treatment with the D1 antagonist SCH-23390 and three new pharmacologic agents, SCH-39166, NO-0756, and A-69024, reported to be D1 antagonists. All putative D1 antagonists were found to antagonize the action of SKF-38393 without reducing the increased locomotion and behavioral responses induced by quinpirole, consistent with an in vivo action on D1 receptors. The potency hierarchy of the compounds against the action of SKF-38393 on activity, from strongest to weakest, was: SCH-39166 equaled SCH-23390 and these were greater than NO-0756, which was greater than A 69024. All compounds were found to antagonize L-DOPA-induced self-mutilatory behavior (SMB) in neonatal-6-OHDA-lesioned rats in a dose-related manner. The potency hierarchy against this behavior, from strongest to weakest, was: SCH 23390, SCH-39166, NO-0756, and A-69024. The correlation between the ED50 for the ability of these drugs to antagonize SKF-38393-induced activity and their ability to reduce SMB by L-DOPA was greater than 0.99. In conclusion, the present findings provide additional evidence in vivo that NO-0756, SCH-39166, and A-69024 are selective D1 receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418307 TI - Rejection associated with early appearance of donor-reactive antibodies after kidney transplantation treated with plasmapheresis and administration of 15 deoxyspergualin. A report of two cases. AB - In two kidney transplant patients, one of whom had panel-reactive antibodies (PRA) before transplantation, a pretransplant negative donor-recipient crossmatch became positive within the 1st week after transplantation. Simultaneously, good graft function deteriorated to a state of anuria. One patient graft biopsy showed a vascular rejection, whilst the other patient biopsy was unrevealing. Both patients were treated with plasmapheresis and a new immunosuppressive drug, 15 deoxyspergualin (DSG). Plasmapheresis was performed for 6 and 9 days, respectively, and DSG was given for 5 days in a dosage of 6 mg/kg body weight per day. One of the patients received methylprednisolone i.v. in addition. During treatment the cross-match became negative and has since remained that way. In both patients the graft function was restored. No adverse effects were seen from the treatment, except for a slight leukocytopenia and thrombocytopenia. PMID- 1418308 TI - Protective effect of a prostaglandin oligomer on liver mitochondria in situ: time shared measurements of fluorescence and reflectance in the cold-preserved rat liver. AB - The protective effect of a new oligomeric derivative of prostaglandin B2, known as OC-5186, was evaluated using time-sharing spectrofluorometry in the cold preserved rat liver. Experiments were divided into three groups: in group A, a 5000 ng dose of OC-5186 was administered via the peripheral vein, 1000 ng via the portal vein, and 200 ng/ml in University of Wisconsin (UW) solution; in group B, the OC-5186 dosage was ten times greater than that in group A; in group C (control group), liver procurement and storage were performed without OC-5186. At 0, 12, and 24 h after cold preservation at 4 degrees C, the liver was perfused for 30 min at 12 degrees C with oxygenized Krebs-Henseleit solution, after which the perfusate was switched to deoxygenized Krebs-Henseleit solution. Time sharing spectrofluorometry was used to follow NADH fluorescence at 450 nm with a 360-nm excitation wavelength, as well as the reflectance of cytochrome aa3 with 605 minus 620 nm from oxidation to reduction. Rate constants of NADH fluorescence and cytochrome aa3 reflectance were used as indices of integrity of the mitochondrial respiratory chain. In group C, the rate constant of NADH fluorescence decreased significantly (P < 0.05) from the control value of 8.31 +/- 0.21 x 10(-3) (sec-1) to 4.97 +/- 0.15 x 10(-3) and 5.58 +/- 0.16 x 10(-3) (mean +/- SEM) at 12 and 24 h after cold preservation, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418309 TI - Efficacy of pyrimethamine for the prevention of donor-acquired Toxoplasma gondii infection in heart and heart-lung transplant patients. AB - Seven (11%) of the first 65 patients who received heart transplants at Papworth Hospital were mismatched for Toxoplasma gondii. Of these, four (57%) experienced T. gondii infection and two died. The remaining two had severe symptoms and received anti-T-gondii chemotherapy for a year after transplantation. In an attempt to reduce the impact of donor-acquired T. gondii in our heart transplant recipients, we decided in April 1984 to give prophylactic pyrimethamine to all T. gondii-mismatched patients. In this study, 7 years later, we review the efficacy of this policy. Five of 37 (14%) patients given prophylactic pyrimethamine acquired T. gondii infection; only one was symptomatic, and none died. This compares with 100% symptomatic infection in the pre-1984 patients, who did not receive prophylactic pyrimethamine. We believe that our experience has shown that pyrimethamine is effective in reducing the incidence and severity of primary donor-acquired T. gondii infection in mismatched heart and heart-lung transplant recipients. PMID- 1418310 TI - Octreotide administration in the treatment of pancreatic fistulae after pancreas transplantation. AB - Among the surgical complications of pancreas transplantation are pancreatic fistulae, which arise rather frequently. Suppression of exocrine secretion with polymers has succeeded in reducing the rate of this complication. Nevertheless, in some instances, pancreatic fistulas may occur. Thirty pancreas transplantations were performed in 27 diabetic patients. In 5 cases a pancreatic fistula occurred and was drained after the insertion of a catheter for the collection of secretions. A serous liquid was collected with a high concentration of amylases (61604 +/- 19562 IU/24 h). Fistula output was 280 +/- 87 ml/24 h. Patients were treated with octreotide, administered subcutaneously in a dose of 300-750 micrograms/day. In all patients a progressive reduction in fistula output was observed after a mean of 16 + 2 days. Fistula flow rate dropped to 24 +/- 10 ml/24 h--a reduction of 95% +/- 5% and drainage was subsequently stopped. Sonographic follow-up did not show recurrence of peripancreatic collections in these patients. All patients were insulin-independent up to 12-44 months after surgery. PMID- 1418312 TI - Transplantation of allogeneic fetal pancreases combined from MHC-different donor strains does not change rejection of the graft. AB - A number of 17.5- to 18.5-day-old fetal pancreases were grafted under the kidney capsule of streptozotocin-diabetic rats. Eight syngeneically grafted glands were sufficient to reverse the diabetes of the recipients within 4 weeks when the recipient rats were treated with insulin for 18 days after transplantation. Eight allogeneic fetal pancreases obtained from one donor strain were rejected after transplantation and the recipients relapsed into hyperglycemia immediately after insulin withdrawal. Eight allogeneic fetal pancreases obtained from eight MHC different donor strains were also rejected and the recipients relapsed into hyperglycemia after insulin withdrawal. Using fetal pancreases as tissue sources, the combination of the allogeneic graft from different donor strains was not sufficient to prolong the survival time of the grafted tissue. PMID- 1418311 TI - Pediatric liver transplantation from neonatal donors. AB - Sixteen recipients of neonatal liver grafts were compared with 114 contemporaneous pediatric recipients of grafts from older donors. Graft and patient survival were worse in the neonatal group although the differences were not statistically significant. Patients with neonatal livers who had no technical complications required a longer time postoperatively to correct jaundice and a prolonged prothrombin time. These functional differences were limited to the 1st postoperative month and the end result was the same as with liver transplantation from older donors. PMID- 1418313 TI - 15-deoxyspergualin treatment of graft rejection in man: effect on mononuclear cells. AB - We studied the effects of 15-deoxyspergualin (DSG) on human mononuclear cells in blood when DSG was administered as anti-rejection treatment to kidney-transplant patients in combination with methylprednisolone (MP) in a safety study. The numbers of leucocytes, lymphocytes and monocytes, the percentages of T and B cells and the expression of the interleukin 2 receptor and the human leucocyte antigen DR locus (HLA-DR) were determined in blood from these patients and from patients treated with MP only. We found that the number of lymphocytes and monocytes decreased in all groups, as also did the CD4/CD8 ratio and the HLA-DR expression on monocytes. DSG counteracted the increase in the number of leucocytes observed in patients treated with MP only. Different effects of DSG and MP were also observed on B cells. While the percentage of CD20+ cells increased in the MP group, it remained unaltered in patients given low-dose DSG and/or was decreased in those given higher doses. Since available evidence suggests an effect of DSG on B-cell reactivity, this drug may become an important addition to the arsenal of immunosuppressive drugs in clinical transplantation. PMID- 1418314 TI - Analysis of prognostic factors affecting renal allograft survival. AB - A total of 201 consecutive cadaveric kidney transplantations were performed in 188 patients at the Chinese Great Wall Hospital, Beijing, from October 1977 to May 1990. The overall 1-, 2-, 5-, and 10-year graft survival rates were 75.5%, 64.5%, 37.0%, and 32.9%, respectively. In the last 5 years, these figures have risen to 83.7% at 1 year, 69.5% at 2 years, and 40.8% at 5 years, respectively. The 14 variables correlating to graft survival in the present study were analyzed using the log rank test for univariate analysis and the Cox proportional hazard model for multivariate analysis. The results show that immunosuppressive drug therapy, cold ischemia time, acute tubular necrosis, and infection were significant factors affecting the survival of cadaveric kidney grafts. Triple therapy with low-dose cyclosporin, as compared to conventional immunosuppressive drug therapy, significantly increased the 1-year graft survival rate (90.3% vs 31.3%) but did not influence the long-term graft survival rate after 3 years. The incidence of acute tubular necrosis significantly correlated to the cold ischemia time and influenced the 1-year graft survival. Analysis showed that the lymphocytotoxic crossmatch affected graft survival after 3 years and that most late graft losses were due to chronic rejection, suggesting that histocompatibility is the strongest factor affecting long-term graft survival. A beneficial effect of pretransplant blood transfusions on long-term graft survival was seen in patients treated with conventional immunosuppressive drugs but not in cyclosporin-treated patients. PMID- 1418315 TI - Endoscopic treatment of vesicoureteral reflux prior to renal transplantation. AB - Endoscopic subureteral injection of Teflon was done in 34 potential renal transplant recipients to correct vesicoureteral reflux. Follow-up ranged from 6 to 24 months. After one injection reflux was corrected in 53.7% of the patients; this increased to 64.8% after a second injection. The procedure is simple, effective, without major morbidity, and avoids the risk of nephroureterectomy. However, efforts must be made to find an ideal substance with a higher biocompatibility and without risk of migration. PMID- 1418316 TI - Monoclonal antibodies in renal transplantation: a review. AB - OKT3 is the first anti-CD3 monoclonal antibody available for treatment in humans. Over the last few years it has proven to be a very powerful immunosuppressive agent in renal transplantation. Clinical studies have shown that OKT3 is superior to high-dose steroids as first-line treatment for acute renal allograft rejection. Furthermore, it is comparable to antithymocyte globulin (ATG) in treating steroid-resistant rejection and is also effective as rescue treatment in ATG- and antilymphocyte globulin-(ALG-) resistant rejection. Despite its excellent rejection-reversal rate, OKT3 treatment is followed by a substantial percentage of re-rejections, most of which respond well to steroids. In the early post-transplantation period, a prophylactic course of OKT3 is very effective in preventing acute rejections, and in this respect it is probably equivalent to ATG. Indirect evidence exists that a prophylactic course of OKT3 may be beneficial in immunologically high-risk patients and in patients with delayed graft function. However, more clinical studies are required to answer the question whether OKT3 should be given as induction treatment, as first-line treatment, or as rescue treatment. To answer this question, the side effects of OKT3 should also be taken into account. First-dose-related side effects, although frequent and disturbing, are usually transient and seldom life-threatening, provided overhydration has been corrected and steroids have been given before the first administration. These side effects are attributed to the release of cytokines as a result of T-cell activation or lysis. After exposure of patients to OKT3 an increased incidence of infections and malignancies has been reported. However, it is not yet clear whether this is due to OKT3 as such, or whether it merely reflects the total burden of immunosuppression. Xeno-sensitization represents an important limitation to OKT3 treatment, although a second or third course can still be effective in patients with low antibody titers. The precise immunosuppressive mechanism of anti-CD3 monoclonal antibodies is yet unknown. Monitoring of patients treated with OKT3 revealed CD3 and/or T-cell antigen receptor depletion and immunological incompetence of remaining T cells. More clinical data are required to establish the correct dose and duration of OKT3 treatment. In conclusion, OKT3 is a powerful immunosuppressive agent but its real value in renal transplantation remains to be determined. A practical approach may be to reserve it for the treatment of steroid-resistant rejections.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1418317 TI - VIP restores natural killer cell activity depressed by hepatitis B surface antigen. AB - Vasoactive intestinal peptide (VIP) has recently been shown to bind to human lymphocytes and modulate immune functions. The ability of VIP in restoring natural killer (NK) cell activity depressed by hepatitis B surface antigen (HBsAg) has been investigated in the present research. Human lymphocytes were incubated with HBsAg and, after washing, a 4-hr cytotoxicity assay was performed. VIP was coincubated with lymphocytes during the preincubation with HBsAg or, alternatively, throughout the cytotoxicity assay. The study revealed that VIP, either preincubated or coincubated in the 4-hr assay, strongly restores NK cell activity depressed by viral antigen. This is noteworthy considering that a number of lymphocyte modulators such as interferons fail in restoring viral-dependent NK cell activity depression. In contrast with previous reports, even when coincubated in the 4-hr assay, VIP is a strong activator of NK cell activity. Further studies will be required to understand which mechanisms are involved in the interrelation between VIP and NK cells during viral infections. PMID- 1418318 TI - Altered macrophage antigen-presenting cell function following Friend leukemia virus infection. AB - To investigate the mechanism by which Friend leukemia virus (FV) causes immunosuppression, the ability of peritoneal macrophages to mediate antigen specific T-cell activation following FV infection was examined. Decreased IL-2 production was observed when antigen-primed T cells were cultured with antigen pulsed macrophages from mice infected with FV, compared to T cells cultured with macrophages from control mice. Macrophages from FV-infected mice demonstrated decreased phagocytic and pinocytic activity, suggesting that antigen uptake may be impaired in these cells. In addition, FV-infected mice had decreased numbers of MHC class II positive macrophages compared to uninfected controls, as measured by immunofluorescence. The alterations in antigen uptake and class II expression observed in macrophages from FV-infected mice may be the result of infection of these cells by FV, which was demonstrated by in situ hybridization using a FV specific probe. The ability of FV to infect and modulate the functions of macrophages may account, at least in part, for the immunosuppression observed in FV-infected mice. PMID- 1418319 TI - Conformation-dependent accessibility of the linear epitopes located on the rabies virus glycoprotein. AB - Seven monoclonal antibodies (MAbs) were derived from mice immunized with the rabies virus glycoprotein of the Pitman-Moore (PM) strain. These antibodies recognized at least five partially overlapping sites located in one immunodominant region. A panel of MAbs was then used to characterize antigenic relationship between PM strain and SAD-Vnukovo strain of these rabies viruses. In immunoblot, all tested antibodies bound to the glycoprotein of both rabies strains, indicating shared antigenic determinants located on the corresponding immunodominant regions. The pattern of reactivity in immunoblot suggested the specificity of antibodies against linear epitopes. However, the supposed close antigenic relation between PM and SAD-Vnukovo strains (evidenced by immunoblot) was not fully confirmed by immunoenzymatic assay. Data provided by ELISA demonstrated two distinct patterns of MAbs reactivity with both antigens. Four antibodies showed specificity for PM strain glycoprotein only, while three MAbs bound with both PM and SAD-Vnukovo strain antigens. We supposed the strain specific conformation of the native glycoprotein to be responsible for selective access of single MAbs to the respective common linear epitopes. PMID- 1418320 TI - Antibodies against p24 of HIV-1 in patients with systemic lupus erythematosus? AB - The involvement of retroviruses in the etiopathogenesis of autoimmunity is discussed. Recently antibodies against p24 of HIV-1 were described in patients from Texas with SLE. Therefore we investigated the presence of these antibodies in our SLE collective (German caucasians and blacks from Michigan) employing ELISA and Western blot. No anti-p24 reactivity was observed in our SLE patients in Western blots, suggesting that there may be ethnological or regional differences between our patients those from Texas. PMID- 1418321 TI - Monoclonal antibody characterization of Jamestown Canyon (California serogroup) virus topotypes isolated in Canada. AB - Jamestown Canyon (JC) virus of the California (CAL) serogroup has been isolated in 12 American states and 6 Canadian provinces. A study was undertaken to produce monoclonal antibodies (MAbs) to JC virus and to use these MAbs to assay for possible heterogeneity among naturally occurring JC topotypes in Canada. MAbs were produced to the prototype strain of JC virus using BALB/c mice. Twenty-seven secreting MAbs were obtained and three of these MAbs were propagated and studied. All three MAbs, M1 (IgG1), M2 (IgG2b), and M3 (IgG2a), were reactive by immunofluorescent antibody assay against JC-infected vero cells and by ELISA against JC antigen. MAb M2 reacted with all members of the Melao complex, MAb M1 reacted only with Keystone virus, while MAb M3 exhibited no reactivity with other CAL serogroup viruses. Only MAb M3 possessed neutralization and hemagglutination inhibition activities against JC virus. The MAbs were also tested by ELISA and for neutralizing activity against 13 JC topotypes isolated in 5 provinces from Newfoundland to Saskatchewan. ELISA confirmed closer identity of the Canadian topotypes to JC as opposed to the closely related South River virus. The MAbs verified all Canadian topotypes to be JC virus but revealed different patterns of reactivity between these topotypes and prototype JC virus. PMID- 1418322 TI - Coping with substance abuse: a many-sided task. AB - Steady progress is being made towards understanding the use of drugs for non therapeutic purposes. The associated problems are increasingly regarded as having psychological, biological and social dimensions. There is a growing acceptance that the hazardous consumption of alcohol and other drugs can both result from and exacerbate poor socioeconomic conditions. Sustained action to combat drug related problems is needed on a broad front; there is no panacea. PMID- 1418323 TI - Myiasis: the battle continues against screwworm infestation. AB - The New World screwworm fly (Cochliomyia hominivorax) caused myiasis extensively among livestock in Mexico and the southern third of the USA until eradication was achieved by repeatedly releasing sterile males of the species on a massive scale. The pest appeared in Libya in 1988, the first time it had become established outside the western hemisphere. Because of the threat of myiasis in animals and people, not only in Libya but also elsewhere in Africa and beyond, a concerted campaign of sterile male releases was mounted with strong international support, and the outbreak has been eliminated. Action is continuing against the pest in Central America. PMID- 1418324 TI - Evaluation of maternal and child health services in Latin America. AB - A methodology has been devised for evaluating the efficiencies of maternal and child health care services in 18 countries of Latin America. The results point towards ways of developing local health systems, strengthening coordination between programmes and services, and utilizing resources more rationally. PMID- 1418325 TI - Health in space--and on Earth. AB - Because astronauts confront unprecedented hazards, manned space exploration has to proceed gradually and cautiously, each new step being taken with the benefit of what has been learned during earlier stages about bodily requirements. As well as helping to protect the lives of astronauts, however, space medicine is proving to have valuable applications in global health care. PMID- 1418326 TI - Rational education for rational therapy. AB - A sound knowledge of pharmacology and clinical therapeutics could help future prescribers in India to master the principles and practice of rational therapy. The teaching of pharmacology in medical schools should be restructured accordingly, and greater attention should be given to the applied aspects of the subject. Practicals in experimental pharmacology and dispensing pharmacy should be discontinued and useful exercises should be introduced. Methods of evaluation should be modified. PMID- 1418327 TI - Action to reduce road casualties. AB - Progress in road safety is reviewed with particular reference to radical measures that have proved beneficial in Australia. Community involvement in decision making is vital if gains are to be made and sustained in this field. PMID- 1418328 TI - Safe travel--a worthwhile destination. PMID- 1418329 TI - Finance for health care: part of a broad canvas. AB - The economic crisis of the 1980s led to cuts in both government and household expenditure on health in the Third World. In order to address these issues it is necessary to adopt a macroeconomic approach to the analysis of the health sector; this allows its relationship to the whole economy to be understood. The efficient and equitable utilization of resources is particularly important in times of severe financial constraint. PMID- 1418330 TI - Risk-sharing in rural health care. PMID- 1418331 TI - Community participation in the control of filariasis. AB - A programme was launched in 1986 for the control of brugian filariasis in an area of high endemicity in southern India. Sustained community involvement was achieved by integrating economic measures to improve the lot of the people with the creation of widespread awareness about the cause of the disease and about the possibilities of combating it. PMID- 1418332 TI - Traditional healers and community health. AB - A review of projects in various countries suggests that traditional healers, if properly trained, can contribute significantly to the work of primary care teams. Recommendations are offered with a view to making the best possible use of this valuable resource. PMID- 1418333 TI - Health systems research--a key to progress. AB - Papua New Guinea has made significant strides towards establishing a capacity in health systems research. This can be expected to strengthen the country's overall health development programme. PMID- 1418334 TI - Defining health systems research. PMID- 1418335 TI - Paradigms old and new. PMID- 1418336 TI - An information service on teratogenic agents in Brazil. PMID- 1418337 TI - Promotion of breast-feeding in the media. PMID- 1418338 TI - Role of traditional birth attendants in the dissemination of advice on nutrition. PMID- 1418339 TI - Parents should know how to take a child's temperature. PMID- 1418340 TI - Innovation in medical education: looking towards the community. PMID- 1418342 TI - Health economics exchange. PMID- 1418341 TI - Joint ventures and fair pricing. PMID- 1418343 TI - Health literature and bibliographic control in Nigeria. PMID- 1418344 TI - Promotion of polio vaccination on television: need for more positive images. PMID- 1418345 TI - Mandatory plain packaging for tobacco products. PMID- 1418346 TI - China's landmark tobacco law. PMID- 1418347 TI - Aftermath of the Armenian earthquake: from emergency aid to cooperation for development. PMID- 1418348 TI - Baseline studies for community development projects. PMID- 1418349 TI - Nurse anaesthetists in the Gambia. PMID- 1418350 TI - Primary surgical care. PMID- 1418351 TI - X-rays: keeping the doses down. PMID- 1418352 TI - Food and drugs: the perils of plenty. AB - The abundance of both food and pharmaceuticals in much of Europe has brought serious health problems as well as benefits. It is no longer possible to assess the quality of most products on the basis of physical examination, and labels often carry information that is incomprehensible to lay persons. Governments should ensure that consumers can understand both the broad principles of healthy living and the nature of the foodstuffs and medicines on offer. It is also important that prescribers be kept abreast of developments in the pharmaceutical field. PMID- 1418353 TI - Challenges and opportunities--one vitamin, two minerals. AB - Millions of people suffer and many die from lack of minute traces of nutrients. Methods of prevention are cheap and simple. Their universal application could yield health and economic benefits comparable to those achieved by smallpox eradication. PMID- 1418354 TI - A better prospect for city life. AB - The WHO "healthy cities" concept is discussed with particular reference to initiatives taken in Rennes, France. An outline is given of the collaboration between cities, both nationally and internationally, in efforts to achieve the health-for-all goals. PMID- 1418355 TI - Which way for housing and human settlements? AB - In order to clarify the housing and settlements component of the European health for-all programme and to identify perceived priorities with a view to the preparation of training materials, members of WHO's Rural and Urban Development and Housing Network were invited to complete a questionnaire. The results are reported below. The questionnaire can be used in identifying local development priorities, comparing attitudes, and studying perceived needs. Intended as a tool for policy-makers, course organizers and public health professionals, it is available from the authors of the present article. PMID- 1418356 TI - Essential books for health workers in the Third World. PMID- 1418358 TI - Sports and recreation for a healthy life. PMID- 1418357 TI - Information support for urban primary health care. PMID- 1418360 TI - Global strategy for the prevention and control of AIDS. PMID- 1418359 TI - Promotion of heart health in schools. AB - The Netherlands Heart Foundation is making a significant contribution to the education of primary and secondary school children on the prevention of cardiovascular disease, within a broad context of encouragement for healthy life styles. Efforts are also being made to ensure that both schoolteachers and pupils enjoy a healthy working environment. PMID- 1418361 TI - "AIDS: a community commitment" is the theme of World AIDS Day 1992. PMID- 1418362 TI - Alzheimer's patients should be included in phase I clinical trials to evaluate compounds for Alzheimer's disease. AB - Dosage and tolerance are critical issues in successful drug therapy for patients with Alzheimer's disease (AD). A clear distinction among patient populations and AD patient subpopulations is necessary to ensure a thorough assessment of new central nervous system-active compounds. Phase I inpatient trials, in which tolerance and safety are evaluated under double-blind conditions in the target population, provide valuable information for use in planning multicenter outpatient trials. In similar studies, even those involving the elderly, tolerance and safety outcomes in healthy volunteers are not always predictable. An early trial of the effects of velnacrine in healthy, elderly, male volunteers was followed by a trial in the target population. A group of volunteers, aged 60 to 74 years who did not have AD, received 300 mg of velnacrine each day. This dosage was well tolerated for 28 days. Diarrhea, generally of moderate severity, was the only reported adverse effect. No subjects were required to discontinue taking velnacrine. In contrast, a similar trial showed a dosage of 300 mg of velnacrine each day intolerable among patients with AD. Adverse reactions to dosages greater than 225 mg/day included dizziness, fainting, nausea and/or vomiting, headache, and severe diarrhea. A velnacrine dosage of 225 mg/day appeared to be safe and well tolerated in a small population of healthy patients with AD. Based on the inpatient experience with AD subjects, a maximum dose of 225 mg/day was adopted for outpatient studies. Although factors that may contribute to drug sensitivity in patients with AD vary beyond conclusive parameters, the observed sensitivity within the target AD group may indicate a safety/tolerance study as a worthwhile antecedent to multicenter efficacy trials. PMID- 1418363 TI - Antidepressant treatment of pathologic laughing or crying in elderly stroke patients. AB - Pathologic laughing or crying (PLC), a complication of many neurologic disorders, involves behavior that is either inappropriate to the context or to the patient's subjective feeling state. It is due to a dysregulation of the motoric components of emotional experience. PLC is distinct from, but often associated with, major depression. The relatively few reports on treatment of PLC are primarily with tricyclic antidepressants. We report the effective treatment of PLC due to stroke in three patients with nortriptyline or fluoxetine. The cases also illustrate the broad spectrum of depressive symptoms (from none to a major depression) seen in patients with PLC. We discuss treatment implications and directions for future research. PMID- 1418364 TI - Alzheimer's disease or plaque disease? Two cases at the frontier of a definition. AB - Atypical dementias confront the adequacy of current diagnostic concepts. The two patients with atypical dementia syndromes described here shared common postmortem features of numerous neocortical neuritic (senile) plaques and microvascular amyloid, sparing of hippocampus and substantia nigra, and the virtual absence of neurofibrillary tangles. Microscopically, the two differed only by the presence of a few subcortical Lewy bodies in case 1. These similar morphologic features were associated with dramatically different clinical presentations. In the first patient, visual hallucinations, Capgras' syndrome, cognitive slowing, myoclonus, parkinsonism, and primitive reflexes evolved over 3 years. Memory and language were relatively spared. In the second, dysphagia, nonfluent aphasia, hypophonia, motor perseveration, and a severe disorder of attention developed during this 18 month illness. At autopsy, an unrecognized colon malignancy was found. Despite high neuritic plaque counts in cortex, neither the clinical nor the pathologic criteria for Alzheimer's disease adequately describe either case. The cases will be examined first as clinical, then as neuropathologic, entities. From this approach, we conclude that a specific clinical dementia syndrome may be expressed by several neuropathologic "diseases" and that a variety of clinical syndromes may represent a single neuropathologic diagnosis. This strategy identifies a conceptual dichotomy between Alzheimer's syndrome and postmortem Alzheimer's disease. Meticulous clinical and neuropathologic observation is essential in advancing an understanding of the relationship between the two. PMID- 1418365 TI - To drive or not to drive: preliminary results from road testing of patients with dementia. AB - There has been considerable debate about whether driving privileges should be revoked from patients with a diagnosis of dementia and whether highway safety policies should come under closer scrutiny for all elderly. Two case studies are reported of patients with a diagnosis of probable Alzheimer's disease who participated in a pilot project to assess driving. Subjects underwent neurologic and neuropsychological evaluation. Caregivers were included in psychosocial assessments. Patients participated in a specially designed driving evaluation, including an actual road test. Although both patients had mild-to-moderate cognitive impairment on standard tests, one of the patients was deemed safe to drive on the road test while the other was not. These preliminary results suggest that driving skill may not be predictable solely on the basis of the office examination. A road competency test provides a more objective and direct measure on which to base a decision of such important consequence. Implications for public policy and the role for healthcare providers in this process are discussed. PMID- 1418366 TI - Successful treatment with pimozide of Capgras syndrome in an elderly male. AB - A case of Capgras syndrome in a 67-year-old man who failed to improve on haloperidol, but responded to pimozide, is described. The patient's paranoid delusions abated with 8 mg per day of pimozide. We believe pimozide's established benefit in the treatment of delusional disorders warrants its consideration in alleviating other delusions, including "the delusion of doubles." PMID- 1418367 TI - The SKT neuropsychological test battery. AB - The SKT is a brief neuropsychological test battery that includes nine performance subtests that define two independent factors of memory and attention deficit. It requires no more than 15 minutes to administer and has five parallel forms. Developed in Germany, it has been used successfully to document improved performance of patients in trials of antidementia drugs in that country. This article addresses factor structure and scoring, dementia profile classification, reliability, and validity data. The SKT appears to hold promise for efficient assessment of objective performance changes to supplement clinical evaluations of therapeutic efficacy of new drugs for treatment of senile dementia. PMID- 1418368 TI - Pattern of use of antidepressants in long-term care facilities for the elderly. AB - Despite some evidence that neuroleptic medication is overused or misused in long term care facilities for the elderly, there has been virtually no attention paid to the pattern of use of antidepressants in these facilities. All patients in long-term care in a geriatric hospital and a home for the aged who were receiving antidepressants were identified; 10.5% of the patients in the hospital and 12.7% in the home for the aged were receiving an antidepressant. The rate of use of antidepressants on the different units ranged from 0% to 26.8%. The most commonly prescribed antidepressant was doxepin followed by nortriptyline. The mean dose of antidepressant was 34.8 mg. Although depression was the most common reason for the prescription of an antidepressant (69% of patients receiving one), other reasons included pain, agitation, aggression, and insomnia. Patients had been receiving antidepressants for up to 10 years, with a mean duration of 32 months. The majority of patients (60%) had a history of depression predating their institutional admission. Patients receiving antidepressants were compared to a group not receiving antidepressants, who were matched for age, sex, unit, and attending physician. Patients receiving antidepressants were more likely to have a history of stroke (33.8% versus 16.9%). There was no significant difference between the two groups regarding the prevalence of dementia, Parkinson's disease, thyroid disease, malignant tumor, congestive heart failure, or diabetes mellitus. Prospective studies are required to determine the efficacy of antidepressants in this population and to identify factors that can predict a positive response to treatment. PMID- 1418369 TI - Limitation of the Mini-Mental State Examination for the detection of amnesia. AB - The present study demonstrates the limitation of the Mini-Mental State Examination (MMSE) for detecting the amnestic syndrome. Although neuropsychological testing yielded severe memory deficits in all of the 11 amnesic patients tested, six of the patients obtained total MMSE scores above the standard cutoff score of 24. Further, only six patients completely failed the MMSE recall item, and three patients performed errorlessly on this item. Results from one postencephalitic patient are presented in detail. She performed the serial sevens task very quickly and subsequently recalled all three of the to-be remembered words. Her performance on other memory tests confirmed that a longer retention interval than that provided by the MMSE is necessary to elicit her memory disorder. PMID- 1418370 TI - The association of normal-pressure hydrocephalus with obstructive sleep apnea. AB - This report describes a 70-year-old man with obstructive sleep apnea who deteriorated rapidly when nasal continuous positive airway pressure was begun. The patient was found to have normal-pressure hydrocephalus, which was possibly exacerbated by the nasal continuous positive airway pressure. A review of the literature indicates several significant associations between apnea, normal pressure hydrocephalus, and increased intracranial pressure and suggests that the association of obstructive sleep apnea and hydrocephalus might not be rare. Implications for diagnosis and treatment are discussed. PMID- 1418371 TI - Induction of TH1 and TH2 responses: a key role for the 'natural' immune response? AB - What pushes a T-cell response towards a predominantly TH1 or TH2 phenotype? Several factors have been proposed, including the properties of antigens, dose of antigen, site of exposure and ongoing immune response in the host. Here, Sergio Romagnani presents new evidence to indicate a determining role for the 'natural' immune response, including NK cells and cells of the mast cell/basophil lineage, in the subsequent 'specific' T-cell response. PMID- 1418372 TI - Immunotoxins: the power and the glory. AB - Immunotoxins are hybrid proteins in which the potent cytocidal action of a toxin is harnessed for the selective destruction of target cells by attachment to a specific monoclonal antibody (mAb) or growth factor. This brief article describes the latest advances in the molecular and cellular biology, pharmacology and clinical evaluation of immunotoxins, as discussed at a recent meeting. PMID- 1418373 TI - Eosinophils 1992. AB - This report from a recent meeting* highlights some of the key developments in eosinophil research and assesses their impact on current views of the role of eosinophils in inflammation. Considerable progress has been made in defining the structure, constituents and properties of eosinophils in vitro and these new insights into eosinophil biology are summarized. A new era is beginning in which the roles of eosinophils can be assessed and defined in vivo. PMID- 1418374 TI - The developmental relationship between NK cells and T cells. AB - NK cells and T cells share many features, suggesting that they have a common origin. Here, Lewis Lanier and colleagues describe recent studies of fetal ontogeny and thymic development that provide support for this hypothesis, and propose an integrated scheme for NK-cell and T-cell development. PMID- 1418375 TI - Immunoglobulins did not arise in evolution to fight infection. AB - The complex interactions between B and T cells in response to external antigens are the major focus of contemporary immunology. Here, John Stewart argues that they may be relatively late evolutionary developments, due to the redeployment of a system invented for other reasons. He suggests that the system of variable region molecules (VRM) arose, at the time of the first vertebrates, by an endogenous, self-organizing process; this primordial VRM system instituted a molecular ecology, a function so important that from then on no vertebrate has been able to do without it. PMID- 1418376 TI - Mechanisms of self tolerance. AB - The redundancy of biological systems minimizes the probability that isolated molecular and cellular defects entail deleterious consequences. This notion also applies to the establishment and maintenance of tolerance to self antigens. Thus, immune homeostasis is attributed to multiple distinct safety valves that are connected in series and intervene at defined control points of the life cycle of the developing lymphocyte to guarantee the physical elimination, functional inactivation, or regulated inhibition of self-reactive, potentially autoaggressive, B and T cells. PMID- 1418377 TI - Diseases associated with HTLV-I: virus, IL-2 receptor dysregulation and redox regulation. AB - HTLV-I, the etiological agent in adult T-cell leukemia, has also been strongly implicated in a number of non-neoplastic T-cell-associated diseases. Here, Junji Yodoi and Takashi Uchiyama review these associations and focus on the emerging concepts of IL-2R dysregulation and redox regulation by adult T-cell leukemia derived factor in the pathogenesis of HTLV-I-related diseases. PMID- 1418378 TI - Insect defensins: inducible antibacterial peptides. AB - In response to bacterial challenge or trauma, insects produce a battery of bactericidal or bacteriostatic molecules with a broad spectrum of activity against Gram-positive and/or Gram-negative bacteria; most are small-sized cationic peptides. This review focuses on insect defensins, a large group of inducible antibacterial peptides that are present both in ancient and recent insect orders. This immune response of insects shares many of the characteristics of the mammalian acute phase response. PMID- 1418379 TI - Arguments against routine adenotonsillectomy. PMID- 1418380 TI - Studies of cytokine receptor expression by cells of the immune system--a waste of time? PMID- 1418381 TI - More evidence for a case for chaperones in antigen processing. PMID- 1418382 TI - The size of the mature membrane receptor for follicle-stimulating hormone is larger than that predicted from its cDNA. AB - A 240 kDa protein isolated from bovine calf testis has been shown to have properties characteristic of an FSH receptor. However, rat testis FSH receptor has, on the basis of cloning experiments, been found to have a much lower molecular mass of 75 kDa (peptide only). To examine this point, the size of the FSH receptor in membranes obtained from cultured Sertoli cells of immature rats was determined after polyacrylamide gel electrophoresis under non-reducing conditions, followed by transfer to polyvinylidene difluoride membranes and direct identification of the FSH receptor by ligand blot analysis utilizing radioiodinated human FSH. In this system, the rat Sertoli cell membrane FSH receptor also showed a molecular mass of 240 kDa. Bovine testis contains LH and FSH receptors. We compared the sizes of FSH and LH receptors present in the same bovine testis membrane preparation by ligand blot analysis. The FSH receptor again showed a molecular mass of 240 kDa, whereas the LH receptor showed a molecular mass of 90 kDa. The latter value is similar to that deduced by cloning techniques (75 kDa, peptide only). The evidence seems to suggest that, whereas the molecular mass deduced for the LH receptor on the basis of its cDNA is similar to that of the mature membrane receptor, the size of the FSH membrane receptor is considerably different from that deduced on the basis of its cDNA, presumably as a result of post-translational processing. The marked difference in size between mature FSH (240 kDa) and LH (90 kDa) receptors may reflect significant structural differences of importance with regard to mechanisms of signal transduction. PMID- 1418383 TI - Design and synthesis of heterofunctional V1a-selective vasopressin receptor ligands with lysine at position 9. AB - A peptide analogue of [8-arginine]vasopressin (AVP) with Lys substituted for Gly at position 9 ([d(CH2)5Tyr(Me)2LysNH2(9)]AVP; ALVP) has been synthesized as a precursor for the production of heterofunctional vasopressin receptor ligands. Three heterofunctional ligands have been prepared by attaching biotin and a photoreactive cross-linker capable of iodination, either alone or in combination, to the epsilon-amino group of Lys at position 9 in ALVP. The binding characteristics of these novel ligands have been determined at the V1a and V2 vasopressin receptors by employing membrane preparations of rat liver and kidney respectively. All of the analogues synthesized during the course of this study bound selectively, and with high affinity, to the V1a vasopressin receptor subtype. Our results demonstrate that the strategies described in this paper provide a convenient means of synthesizing heterofunctional vasopressin receptor ligands with preservation of subtype-specific, high affinity binding characteristics. These parameters establish the potential value of the analogues as probes for investigating V1a receptor structure and function. PMID- 1418385 TI - Regulation of steady-state follistatin mRNA levels in rat granulosa cells in vitro. AB - The regulation of steady-state follistatin mRNA levels by different pituitary hormones and peptide factors was examined in granulosa cell cultures derived from diethylstilboestrol-treated immature rats. Cytosolic RNA from cell cultures was prepared by lysis and equal amounts of RNA from all samples were analysed with a solution-hybridization assay using a 32P-labelled antisense probe corresponding to a part of exon 5 together with a part of the 5' end of exon 6 of the rat follistatin gene. In addition, a specific 35S-labelled probe for cyclophilin was used as an internal standard. The results show that 5 micrograms FSH/l for 24 to 72 h stimulated steady-state follistatin mRNA levels, reaching levels 18.5-fold higher than controls. LH (0.2-100 micrograms/l) had only minor effects on follistatin mRNA levels in FSH-primed granulosa cells and prolactin, GH and IGF-I did not show any significant effects. Activin raised basal as well as FSH stimulated steady-state follistatin mRNA levels up to ten- and twofold above controls respectively, whereas epidermal growth factor was found to inhibit FSH stimulated follistatin mRNA levels in a dose-dependent manner. It is concluded that follistatin mRNA levels in granulosa cells are regulated by FSH rather than LH, and that the stimulation by FSH can be inhibited by epidermal growth factor but enhanced by activin. Activin alone was also capable of stimulating follistatin mRNA. PMID- 1418384 TI - Hormonal control of insulin-like growth factor-II gene expression in the rat liver. AB - IGF-II in the rat is an embryonic/fetal growth factor. Transcription of its gene falls abruptly in the liver at about 18-20 days postnatally. In an attempt to elucidate the mechanisms controlling this phenomenon, we used Northern analysis to investigate the effect of corticosterone and thyroid hormones (tri iodothyronine and tetra-iodothyronine) on hepatic IGF-II mRNA levels. The administration of either corticosterone or tri-iodothyronine to 8-day-old pups resulted in a significant decrease in IGF-II mRNA when the animals were examined on day 12 of life. Adrenalectomy, thyroidectomy or adrenalectomy combined with thyroidectomy were, however, without effect. Our results indicate that glucocorticoid and thyroid hormones are not the exclusive regulators of IGF-II gene transcription in the rat liver, but participate in this process, which appears to involve multifactorial interactions. PMID- 1418386 TI - Extra-pancreatic expression of the rat islet amyloid polypeptide (amylin) gene. AB - Messenger RNA for rat islet amyloid polypeptide (IAPP) has been identified not only in the pancreas but also, in lesser amounts, in preparations from the stomach and dorsal root ganglia. In the stomach, insulin mRNA was not detectable, ruling out possible contamination by pancreatic tissue. Because IAPP and calcitonin gene-related peptide (CGRP) are related and CGRP is present in both stomach and dorsal root ganglia, it was possible that 'IAPP' signals were in fact due to cross-hybridization with CGRP mRNA. A second IAPP probe was constructed which does not cross-react. This probe also detected mRNA in both tissues, confirming the expression of IAPP in both tissues. The regional distribution of IAPP mRNA in the stomach did not parallel that of gastrin mRNA. IAPP mRNA was present in the antrum, centrum and pylorus and, like gastrin, the highest amounts were in the pylorus. However, the ratio between the pylorus and centrum was 3.6:1 for IAPP and 156:1 for gastrin. The effects of dietary manipulation were determined; a period of 48 h of starvation reduced pancreatic IAPP mRNA by approximately 60%, whereas in the stomach there was no significant reduction. If the action of IAPP was hormonal, pancreas and stomach would not be acting in concert. A paracrine role for gastric IAPP therefore seems more likely. PMID- 1418387 TI - Membrane permeability to K+ and the control of aldosterone synthesis: effects of valinomycin and cromakalim in bovine adrenocortical cells. AB - Stimulation of aldosterone synthesis by angiotensin II (AII) is associated with depolarization of the cell membrane. Since the potential difference of adrenocortical cells is dependent on membrane permeability to potassium ions, the effects of agents which hyperpolarize the cell (by increasing permeability to K+) on the control of aldosterone synthesis were investigated further. Basal and AII stimulated aldosterone synthesis was increased by 20-70% in cells incubated with 1 or 10 nM of the potassium ionophore valinomycin; higher concentrations markedly inhibited AII-stimulated synthesis. Cromakalim, a potential antihypertensive drug which facilitates the opening of K+ channels in smooth muscle cells, stimulated basal aldosterone synthesis at 2 microM but had no effect at 40 microM. AII stimulated aldosterone synthesis was not affected by cromakalim except at 40 microM, which was inhibitory. The inhibitory effects of cromakalim, unlike those of valinomycin, were not reversible. Aldosterone synthesis from added hydroxycholesterol and pregnenolone (but not from deoxycorticosterone and corticosterone) was significantly inhibited by 40 microM cromakalim. Potassium efflux from cells preloaded with 43K was unaffected by low concentrations of valinomycin, but was markedly increased by concentrations which inhibited AII stimulated aldosterone production. Small decreases and increases in 43K efflux, caused by 1 and 40 microM cromakalim respectively, corresponded with increases and decreases in basal aldosterone production; cromakalim did not affect 43K efflux from AII-stimulated cells. We suggest that increasing adrenocortical cell membrane permeability to K+ reduces steroidogenesis, but that valinomycin and cromakalim have other actions which complicate the relationship between 43K efflux and aldosterone production. Cromakalim appears to inhibit 21-hydroxylase activity in the biosynthetic pathway and may also affect 3 beta-hydroxysteroid dehydrogenase activity. PMID- 1418388 TI - Microheterogeneity of pituitary follicle-stimulating hormone in male rats: differential effects of the chronic androgen deprivation induced by castration or androgen blockade. AB - Testicular androgens are known to influence not only the secretion but also the bioactivity and molecular composition of pituitary FSH. In the present study, we investigated the effects of chronic androgen blockade and castration on the molecular heterogeneity of the gonadotrophin. Groups of male adult rats (five animals per group) received one of the following treatments: vehicle, the non steroidal anti-androgens casodex (20 mg/kg per day) or flutamide (20 mg/kg per day), or castration. After 8 weeks, the animals were killed and individual pituitary homogenates fractionated by isoelectric focusing (IEF) on sucrose density gradients in the pH range 2.5-8. FSH was measured by radioimmunoassay (RIA) in the individual fractions and by invitro bioassay (Sertoli cell aromatase bioassay) in pools of fractions which were combined according to pH intervals of 0.5 units. Bioactive and immunoreactive FSH were also measured in sera and unfractionated pituitary extracts. Testosterone and inhibin were assayed in sera by RIA. A significant increase in serum immunoreactive and bioactive FSH was demonstrated in flutamide-treated and castrated animals, whereas the pituitary content of bioactive FSH remained unchanged in the four groups. Serum testosterone and inhibin were undetectable in castrated animals and significantly increased in those treated with flutamide. By RIA, the IEF profiles of the flutamide-treated and castrated rats showed a significant reduction of the FSH isoforms with 3.5 < pI < 4, with a significant increase in the isoforms with pI > 4 only in the castrated group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418389 TI - [Measurement of mediators in drug allergies. Preliminary study]. AB - Drug allergy is still a region where diagnosis remains difficult. It relies on clinical history, sometimes skin tests and lymphoblast transformation tests, though only when the antigen is soluble. Provocation tests may, if there is a doubt, prove the involvement of the drug. It may be made objective by the measurement of mediators: ECD and tryptase, thus showing the involvement of eosinophils and mastocytes. Should change in these mediators be associated with a syndromic reaction or is it on its own, a diagnostic factor? A complementary study with a reference group, on a sufficient number of patients has allowed, with the assistance of a statistical analysis, better objectivity from the results. PMID- 1418390 TI - [Occupational asthma caused by isocyanates]. AB - The aim of our study is to find whether the percentage of RAST positives to isocyanates within a company is a reflection of the exposure of the workers. Specific IgE was sought in 199 workers from ten companies where isocyanates were used. Twenty of them were followed for some time (june 87 to september 90). A non exposed reference group was used for comparison. Measurements were made by the Pharmacia RAST-ELISA Method. In some cases, controls were made by RAST-RIA and CAPS ELISA/RIA. Results show that the proportion of positive RAST varies from one organisation to another and is probably a measure of the type and intensity of the exposure; the improvement of the working conditions to reduce the ambient concentration reduces, in time, the proportion of positive RAST; there were no positive RAST in the reference group; the conditions of taking and storage of blood samples before analysis influences the result. In conclusion, measurement of specific IgE may be an useful alternative to measurement of ambient concentration for following workers exposed to isocyanates. PMID- 1418391 TI - [Measurement of specific IgE (sIgE) using the MATRIX technique]. AB - In this study, on 34 subjects, the technique for measurement of sIgE by the MATRIX technique has been compared with the reference of CAP RAST, skin tests and clinical history. The two techniques of CAP RAST and MATRIX are judged to be comparable (correlation percentage 88.2%). The results obtained with four allergens [D. pteronyssinus, Timothy grass (Phleum pratense), cat and dog] done separately confirm the reliability of the technique. The study was completed by a comparison of the advantage and disadvantages of CAP RAST and MATRIX. This shows that the manipulation time is much reduced, but with a longer delay time and high reagent cost. In contrast, it has the enormous advantage of using a standardised range of allergens. PMID- 1418392 TI - Combined treatment of allergic rhinitis with terfenadine and nimesulide, a non steroidal antiinflammatory drug. AB - Thirty patient with allergic rhinitis sensitized to Parietaria pollen were enrolled in a double-blind clinical trial in order to evaluate whether the addition of nimesulide, a non-steroidal antiinflammatory drug, to standard antihistamine therapy may improve symptom relief. Patients were randomly divided in two groups: one was given terfenadine (120 mg/day) and nimesulide (200 mg/day), the other was given terfenadine (120 mg/day) and placebo. Both treatments lasted 30 days. Clinical efficacy was assessed by physical examination on 1st, 15th, 30th day of treatment, daily self-evaluation of symptom score, and patient's overall judgement at the end of the trial. The group receiving terfenadine + nimesulide reported a significant lower symptom score and gave a better overall evaluation than the group receiving terfenadine + placebo. These results suggest that the addition of nimesulide to antihistamine treatment may be useful to achieve a better relief of symptoms in allergic rhinitis. PMID- 1418393 TI - Plasma osteocalcin concentrations in cows around parturition. The influence of a regular versus a very short dry period. AB - Plasma Ca, P, Mg and OC concentrations were compared between 2 groups of Holstein cows around 2nd calving. Thirteen cows were milked until their daily milk production was lower than 2 kg, which occurred 4 d before parturition. The control group (8 cows) was normally dried 8 weeks before the expected time of calving. Apart from the week following the initiation of the dry period where plasma OC concentrations were significantly lower in dried cows than in the control group (which would indicate lower bone remodeling in dried cows), no significant difference concerning Ca, P, Mg and OC concentrations were observed between the 2 groups of cows. This indicates that the only lack of 1 8-week-long dry period probably has no major immediate effect upon Ca and bone metabolism in young dairy cows given a convenient Ca and P daily intake. Nevertheless, the lack of the dried period might protect the cow against parturient hypocalcemia: the decrease in plasma Ca and P concentrations observed 12 h after calving was less intense in non-dried cows than in controls. PMID- 1418394 TI - Degradation of maize stem by two rumen fungal species, Piromyces communis and Caecomyces communis, in pure cultures or in association with cellulolytic bacteria. AB - Two species of rumen fungi, Piromyces (Piromonas) communis FL and Caecomyces (Sphaeromonas) communis FG10, were cultured alone or in association with the cellulolytic bacteria Ruminococcus flavefaciens or Fibrobacter succinogenes on maize stem. A kinetic study of the degradation of the substrate was then made. After 48 h of culture, all non-lignified tissues observed by scanning electron microscopy disappeared with P communis and degradation was as complete as that observed in the rumen. In contrast, C communis degraded little of the plant cell walls. The ability of P communis to more rapidly degrade maize stem was probably due to the presence of filamentous rhizoids. The extent of dry matter loss after 8 days of incubation was practically the same in all the monocultures and in the 4 cocultures. However, the rate of degradation was faster in the bacterial than in the fungal monocultures and the co-cultures. No metabolic interaction was observed. PMID- 1418395 TI - Follicular dynamics, plasma metabolites, hormones and insulin-like growth factor I (IGF-I) in lactating cows with positive or negative energy balance during the preovulatory period. AB - The effect of dietary energy balance (EB) on growth of ovarian follicles was tested. Cows (n = 9) were fed a high energy diet (HE diet; positive EB; n = 4) or switched to a low energy diet (LE diet; negative EB; n = 5) during the preovulatory period. Non-esterified fatty acids (NEFA) were greater in cows fed the LE diet. Concentrations of luteinizing hormone (LH) were similar in HE and LE cows. However, the growth of preovulatory follicles in cows fed the LE diet was 50% that of cows fed the HE diet. Insulin-like growth factor-I (IGF-I) in plasma was less in LE-fed cows compared with HE-fed cows, and plasma IGF-I was positively correlated to estrogen: progesterone ratio in follicular fluid of dominant follicles. In summary, slower follicular growth in cows fed an LE diet occurred despite normal plasma LH and coincided with reduced IGF-I and elevated NEFA in plasma. PMID- 1418396 TI - Feeding behavior in rats on a complete diet containing Concanavalin A. AB - Canavalia ensiformis is a tropical legume which could be used in animal feeding. However, it contains a lectin, Concanavalin A (Con A) which is harmful to animals. When rats are presented with a diet containing Con A, rejection of the food appears very soon after the beginning of ingestion. In order to examine this rejection phenomenon 3 studies were carried out. The rejection was found not to be due to a neophobic response, nor could it be attributed to a conditioned taste aversion. The gastric intubation study suggested the hypothesis that it could be the binding of the lectin to the glycosylated molecules from the gut membrane which impaired absorption and hence food intake. PMID- 1418397 TI - [In vitro simulation of rabbit cecal fermentation in a semi- continuous flow fermentor. I. Role of food substrate pretreatment]. AB - A Rusitec semi-continuous flow fermentor was used to study the influence of enzyme pretreatment of food substrates on the fermentation profile over a 2-week period following inoculation with rabbit caecal contents. Three types of substrate were examined: 1) homogenized commercial rabbit feed; 2) the solid remains of this feed after digestion with alpha-amylase for 24 h; and 3) substrate 2 digested for 4 h with pepsin (double enzyme treatment). One of a pair of nylon pouches containing 15 g substrate was replaced each day, thus producing a uniform 48-h fermentation. Fermentation of the untreated feed (1) for 5-6 days produced a fermentation profile quite different from that obtained in vivo in the rabbit caecum: propionic acid accounted for over 35% of total volatile fatty acid (VFA), and butyric acid for about 15%. Amylase digestion (2) gave a stable ferment profile closer to the in vivo profile, except that propionic and butyric acids were similar at 15% of total VFA. Digestion with both amylase and pepsin (3) produced a stable fermentation profile very close to the in vivo profile: C2 > 60%, C3 < 11% and 17% < C4 < 21%. The rate at which membrane constituents (acid detergent fibre, ADF) were lost in 48 h was similar to the digestibility coefficient measured in vivo by others for the same basic feed. Lastly, there was a high percentage (about 5%) of volatile C5 fatty acids; this could be due to the discontinuous fermentor input of one pouch per 24 h. Thus, feed pretreated with both amylase and pepsin simulates, in vitro, rabbit caecal fermentation in a semi continuous Rusitec type fermentor. PMID- 1418398 TI - [In vivo study of cecal fermentation activity in the rabbit. Completion and validation of a new technique for cecal cannulation]. AB - A new technique for caecal cannulation in adult rabbit was validated in order to perform in vivo studies of caecal fermentation under a physiological status. The cannulation did not modify the digestibility of the diet, and it was possible to collect digesta (10 g fresh matter) after a few minutes without stress for animals only 10 days post-surgery. Volatile fatty acid (VFA) (60 mM/l) and ammonia (11 mM/l) concentration of caecal digesta collected in vivo was not different from that obtained from slaughtered rabbits. VFA measurements were reproducible (CV = 6.8%) and were not dependent on the daily collection frequency (1-5/day). Caecal VFA level in the starved rabbit was very low (23 mM/l) while the butyrate/propionate rate was the inverse (C4/C3 = 0.6). Five h after feeding, the in vivo VFA level reached 96 mM/l and the butyrate proportion (12%) over reached those of propionate (3.5%). The caecal fermentations of a 7-week-old rabbit differed from those of an adult by a higher VFA level and by a greater post-feeding variation in the fermentation pattern. PMID- 1418399 TI - Influence of the method of forage conservation on feeding behaviour, intake and characteristics of reticulo-rumen content, in sheep fed ad libitum. AB - The influence of silage conservation methods on eating behaviour and the characteristics of reticulo-rumen contents was studied in sheep by comparing 3 forages, a silage without additive (WAS), one with additive (FAS) and hay (H), prepared from the same cut green forage. The sheep were rumen fistulated. WAS was very badly and FAS poorly preserved while the hay was dried under favourable conditions. The forages were fed ad libitum and the dry matter (DM) intake was 1,054, 1,241 and 1,469 g/day for WAS, FAS and H respectively. There was a single feeding in the morning. At the main meal, DM intake was 270, 317 and 388 g/day and ingestion rate 4.76, 4.56 and 4.16 g of DM/min for WAS, FAS and H respectively. There was slight recovery in ingestion around 16-19 h with hay and FAS but not with WAS. With hay, rumination lasted much longer than with the silages and began sooner after the end of the main meal. In contrast, overall rumination efficiency was the same for hay and FAS. There were fewer contractions of the reticulo-rumen with both WAS and hay. The amounts of reticulo-rumen contents were comparable for the 2 silages and higher for hay. The amounts of NH3 in the contents were the same with WAS and hay but greater with FAS. With WAS, contents were richer in butyric, valeric and caproic acids. The DM turnover rate of the contents was the same for FAS and hay and lower, but not significantly, for WAS. Accordingly, with silage, satiety seems to be rapidly reached but there was no evidence that organoleptic factors were involved. There were no problems with the digestion rate of silages. However, the factors limiting silage intake persisted throughout the diurnal cycle, and reticulo-rumen fill was affected. The more poorly preserved the silage the more these factors reduced the duration and volume of the meals, or both. PMID- 1418400 TI - Ultrastructural study of sex inversion in a protogynous hermaphrodite, Epinephelus microdon (Teleostei, Serranidae). AB - Sex inversion of Epinephelus microdon, a protogynous hermaphrodite was studied using light and electron microscopic criteria. The sex changes takes place within ex-ovarian lamellae in which, in addition to spermatogonia, numerous primordial germ cells (PGCs) were detected. These undifferentiated and bipotential early germ cells are involved, as well as spermatogonia, in the building up of the testis. PMID- 1418401 TI - Sera from preeclamptic women specifically activate human umbilical vein endothelial cells in vitro: morphological and biochemical evidence. AB - Endothelial cell dysfunction could explain many of the pathophysiological changes observed in preeclampsia. Markers of endothelial cell activation including increased circulating Von Willebrand factor (VWF) and cellular fibronectin (cFN) antedate clinically evident disease. We have therefore proposed that alteration of endothelial cell function by circulating agent(s) produced by the placenta initiates the clinical syndrome. This hypothesis predicts that there are a factor(s) in the blood of women with preeclampsia that are capable of altering endothelial cell function. We and others have examined in vitro interactions of maternal serum and endothelial cells to test this hypothesis. Our initial report indicating increased release of [51Cr]chromate from human umbilical vein endothelial cells (HUVE) suggested a lethal, lytic effect of serum from preeclamptic women. However, more specific indicators of endothelial cell structure and function do not support such a nonspecific effect. The morphology of HUVE was minimally altered after exposure to sera of preeclamptic women, and the entry of propidium iodide entry into cells, a sensitive indicator of membrane integrity, also was not increased. These findings, in combination with the increased expression of mRNA for platelet-derived growth factor (PDGF), suggest endothelial cell activation rather than cell death in response to sera from preeclamptic women. Comparison of the effects of endotoxin and sera from preeclamptic women also supports the specificity of this response. Whereas endotoxin strikingly increased VWF on the surface of HUVE and tissue factor activity in conditioned media while minimally increasing cFN, preeclamptic sera increased cFN but had no demonstrable effect on VWF or tissue factor activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418402 TI - Interleukin-1 alpha and interleukin-1 beta in preterm and term human parturition. AB - Interleukin-1 (IL-1) has been implicated in the mechanism of human parturition in the setting of infection. The purpose of this study was to determine the effect of labor (term and preterm) and microbial invasion of the amniotic cavity on amniotic fluid (AF) concentrations IL-1 alpha and IL-1 beta. AF was retrieved by transabdominal amniocentesis from the following groups of women: midtrimester genetic amniocentesis (16 to 18 wk) (N = 15), preterm labor with intact membranes (21 to 36 wk) with or without infection (N = 72), preterm premature rupture of membranes (PROM) (N = 88), and term not in labor or in active labor with or without infection (N = 58). AF was cultured for aerobic and anaerobic bacteria as well as Mycoplasmas. IL-1 was measured with a commercially available immunoassay validated for AF (sensitivity: IL-1 alpha, 157 pg/ml; IL-1 beta, 50 pg/ml). All women at midtrimester had undetectable AF IL-1 alpha and IL-1 beta. Among women in preterm labor with positive AF cultures, IL-1 alpha and IL-1 beta were detectable in the AF in 86.6% (13/15) and 100% (15/15), respectively. In contrast, all women with negative AF cultures without labor (N = 36) had undetectable AF IL-1 alpha concentrations and 52.7% (19/36) had undetectable AF IL-1 beta concentrations. Histopathological chorioamnionitis was present in 92.8% (13/14) of patients who had positive AF cultures and detectable IL-1 in the AF. IL-1 was significantly higher in patients with preterm PROM, labor, and positive AF cultures than in the other subgroups of patients with preterm PROM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418403 TI - Update on immunotherapy for recurrent pregnancy loss. AB - Results of recent, randomized, placebo-controlled clinical trials have raised questions about the efficacy of immunotherapy for recurrent spontaneous abortion (RSA). Most of the clinical trials have shown a 70% successful pregnancy rate with immunotherapy. The controversy comes from variations in success rates in the control populations, which have ranged from 29% to 76%. Explanations for these variations includes small sample sizes and heterogeneity by the populations studied as well as cointervention by the placebo. A meta-analysis has been proposed to investigate these explanations. Because the trials have largely used husband's leukocytes for immunization, alternative forms of immunotherapy have been sought. Two treatments that have been proposed but have not completed testing a randomized, placebo-controlled trials are intravenous immunoglobulin (IVIG) and immunization with seminal plasma. A safe and efficacious method is needed to treat recurrent spontaneous abortion; it is hoped that results of proposed studies will answer this controversy. PMID- 1418404 TI - Association between infertility and spontaneous abortion. AB - Women experiencing recurrent spontaneous abortion have a higher frequency of infertility than that expected in the general population. To further define the relationships between infertility and spontaneous abortion, the obstetrical histories of 43 women with unexplained secondary infertility were evaluated for the frequency of spontaneous abortion. Of the 88 pregnancies studied, 39 (44%) resulted in spontaneous abortion. Women with unexplained secondary infertility experienced a three-fold increase (P less than 0.0001) in the frequency of spontaneous abortions and half the number of live births (P less than 0.0001) compared with the general population. We conclude that the association between infertility and spontaneous abortion includes a higher frequency of spontaneous abortion among infertile couples as well as a higher prevalence of infertility among recurrent spontaneous aborters compared with the general population. PMID- 1418405 TI - Evaluation of immunological infertility. AB - To evaluate the frequency with which immunological factors are associated with infertility, 92 couples with unexplained infertility were studied by using assays to detect anti-sperm antibodies (ASA), human leukocyte antigen tissue types (HLA), lymphocytotoxic antibodies (LCA), and inhibitors of mixed lymphocyte culture (MLC) and mouse blastocyst assay (MBA). Seventy-three of the women had blood assayed for antiphospholipid antibodies (APA). The frequencies of APA, ASA, LCA, inhibitors of MLC and MBA, as well as HLA associations previously reported to be related to infertility (B locus blanks, single DQ locus in offspring, greater than 1 DR sharing between mates) among 92 infertile couples were compared with those observed among 41 fertile control couples. No significant differences in the frequencies of APA, ASA, MBA, and HLA associations between fertile and infertile couples were observed. Fertile couples demonstrated the presence of wife anti-husband LCA and MLC inhibitors more frequently than did infertile couples (51% vs. 8%, P = 0.0001 and 29% vs. 4%, P = 0.002, respectively). While APA, ASA, HLA tissue typing, LCA, and MLC and MBA have been previously reported as being markers of autoimmune and alloimmune responses relating to reproductive outcome, the current data suggest that more specific markers are necessary to diagnose immunological components of infertility. PMID- 1418406 TI - New concepts in ovarian regulation: an immune insight. AB - The purpose of the ovary is to produce eggs. In the human, oocyte production occurs cyclically at monthly intervals. The control of egg production is provided by both the endocrine and immune systems. Successful oocyte production is the result of sophisticated communication between the two systems. These interactions allow adaptive processes necessary for continuation of the species. PMID- 1418407 TI - Sperm antibodies. AB - Anti-sperm antibodies (ASA) occur in 1% to 30% of infertile couples. Mechanisms by which ASA impair fertility include prevention of fertilization by decreasing acrosome reaction and/or zona pellucida binding, and postfertilization effects. Treatment for ASA involves assisted reproductive technologies. PMID- 1418408 TI - Characterization of the anti-cancer activity of transferrin-adriamycin conjugates. AB - The anthracycline anti-cancer drug adriamycin (Adr) was coupled to human transferrin (Trf) by using a glutaraldehyde technique. The effect of Trf-Adr conjugates and unconjugated Adr on human cells was determined by using normal peripheral blood mononuclear cells and chronic myelogenous K562 cells. Cytotoxicity was determined by using an assay that measures the conversion of a tetrazolium salt (MTT) into a purple product (formazan) by mitochondrial dehydrogenases in viable cells. We found that free Adr at a concentration of 1 x 10(-7) had little effect on K562 cells, while Trf-Adr conjugates inhibited 75% of cellular activity. When normal peripheral blood mononuclear cells were tested against Trf-Adr conjugates, the 50% inhibitory concentration was found to be 1.4 1.7 x 10(-6) M, at which concentration greater than 85% of K562 cells were inhibited. Interactions of Trf-Adr conjugates with plasma membrane energy producing systems are the proposed mechanisms of cytotoxicity. PMID- 1418409 TI - Proto-oncogenes and germ-cell differentiation. AB - Oncogenes are identified functionally by their ability to induce neoplastic transformation of susceptible cells. The first oncogenes to be characterized were isolated from acutely transforming retroviruses. Subsequently, it was determined that the retroviral oncogenes were formed from normal, progenitor genes. These cellular homologs of the viral oncogenes are termed proto-oncogenes. The derivation of oncogenes from proto-oncogenes is the consequence of mutations that remove regulatory constraints from the proto-oncogene. The ability of oncogenes to induce transformation implies that proto-oncogenes may function in growth and differentiation pathways in normal cells. Although many proto-oncogenes have been defined, the normal physiological function of most is not known. Studies of proto oncogene expression during normal gametogenesis have determined that some genes are expressed in a stage-specific manner. The use of germ cells to provide homogeneous and defined normal cell populations facilitates identifying the roles proto-oncogenes have in regulating cell growth and differentiation. PMID- 1418411 TI - A cohort study of maternal HLA-DR homozygosity and increased risk for fetal loss. PMID- 1418410 TI - Efficacy of immunotherapy for unexplained recurrent spontaneous abortion: the role of guidelines and meta analysis. PMID- 1418412 TI - Main histocompatibility complex and reproductive system. PMID- 1418413 TI - Report from the Ethics Committee for Immunotherapy. PMID- 1418414 TI - Antiphospholipid antibodies--lobsters or red herrings? PMID- 1418415 TI - Danazol suppresses both spontaneous and activated human lymphocyte-mediated cytotoxicity. AB - Danazol is an effective drug in the treatment of endometriosis. Previous reports suggest that it can act by influencing the immune system. Thus, in this study we evaluated whether danazol is able to affect the expression of natural and activated cytotoxicity by human peripheral blood lymphocytes (PBL). A cytotoxicity assay by 51Cr release was performed to determine the effect of danazol on lymphocyte cytotoxic response toward an erythroleukemic cell line (K562). A significant suppression of spontaneous cytotoxicity was observed when lymphocytes were pretreated for 18 h with danazol at the concentration of 5 x 10( 6) M. In addition, danazol could significantly inhibit both IL-2- and INF alpha activated cytotoxicity at the concentration of 10(-5) M. Following 18 h exposure to danazol, PBL were able to completely recover their spontaneous but not activated cytotoxic potential upon further in vitro incubation (18 h) in absence of the drug. The biological significance of danazol as an inhibitor of immune function under experimentally defined conditions is discussed in relation to its possible role in vivo. PMID- 1418416 TI - The effect of peritoneal macrophage-derived factor(s) on ovarian progesterone secretion and LH receptors: the role of calcium. AB - Macrophages and their secretory products, cytokines, play an integral role in many reproductive processes. In this study we examined the effect of conditioned media from cultured human peritoneal macrophages on progesterone production by granulosa cells and the role of calcium in this process. Macrophages were pretreated with various concentrations of a calcium channel blocker (verapamil) or a calcium ionophore (A23187). Macrophage-conditioned media (MCM) or cell-free media that contained calcium channel modifiers were added at three dose levels to cultured porcine granulosa cells. Progesterone production and LH receptor content were determined. Macrophage-conditioned media alone elevated basal progesterone production, but significantly attenuated granulosa cell LH receptor content. These effects were neither potentiated nor suppressed by pretreating macrophages with verapamil. However, production of the LH receptor lowering factor(s) appeared to be suppressed by calcium ionophore. We conclude that (1) one or more factors produced by macrophages have a net stimulatory effect on basal progesterone production and these factor(s) may not be calcium-dependent and (2) macrophage-derived secretory products reduce granulosa cell LH receptor content. The production of these factor(s) may be calcium-dependent. PMID- 1418417 TI - In vitro sperm capacitation to treat antisperm antibodies bound to the sperm surface. AB - Our objective was to study antisperm antibody bound to the acrosome region during in vitro capacitation and to determine whether acrosome-antibody free sperm can be obtained from previously acrosome-antibody-coated sperm. The spermatozoa from a selected series of 14 patients were tested for sperm antibodies bound to the sperm surface using d-IBT and focusing on the acrosome positivity. The tests were carried out before the incubation and after 3, 6, 9, and 12 h of incubation in Tyrode's solution with 0.5% human serum albumin as the capacitation medium. Tests to evaluate acrosome region, sperm motion parameters, and zonae binding ability were carried out. In this way we were able to evaluate sperm function during capacitation protocol. The patients were 14 subjects selected according to good seminal characteristics, good post-rise sperm parameters, and high percentage of ASA bound to the sperm surface. In all cases the results showed that antisperm antibodies bound to the acrosome region were shed prior to the acrosome reaction. During sperm capacitation in human a modification, migration, or shedding of plasma membrane molecules takes place. The presence of antibodies in such an important area of the sperm head could certainly interfere in the fertilization process. Our data indicate that in vitro capacitation could provide an in vitro therapy capable of eluting antibodies from the acrosome region. PMID- 1418418 TI - A rat cytotrophoblast antigen defined by a monoclonal antibody. AB - A monoclonal antibody that recognizes specifically a cytotrophoblast antigen was obtained. The monoclonal antibody 22H6 was tested on rat choriocarcinoma (in vivo, in vitro), normal placenta, ectoplacental cone, blastocysts, and several normal organs. The antigen was detected on frozen sections and on tissue culture by indirect immunofluorescence. The monoclonal antibody 22H6 reacts with the cytotrophoblasts of rat choriocarcinoma. The giant cells do not display a positive reaction. It is not expressed on other tumors than choriocarcinoma. In adult rats the only cells revealing a positive reaction are the hepatocytes and the epithelial cells lining the small intestine. In the pregnant rat, the antigen is expressed on the cytotrophoblasts of the junctional zone in the placenta, but not on the giant cells. The mab reacts only with the small trophoblast cells of the ectoplacental cone, but not with trophectoderm of blastocyst. The mab has an IgG2b isotype and is not cytotoxic for choriocarcinoma cells in a complement dependent cytotoxicity test. The described monoclonal antibody is to our knowledge the only known marker of rat benign and malignant cytotrophoblast. PMID- 1418419 TI - A call for the lactation initiator: setting the standards. PMID- 1418420 TI - Breastfeeding/lactation and the medical school curriculum. PMID- 1418421 TI - Writing effective letters to the editor. PMID- 1418422 TI - Abrupt weaning: is breast-binding effective? PMID- 1418423 TI - Cabbage leaves: an effective treatment for swollen tissues. PMID- 1418424 TI - Supplementation of breastfed infants: does continuing education for nurses make a difference? AB - Supplementation of breastfed newborns in the first few days of life is a common practice that interferes with the establishment of lactation and is related to early cessation of breastfeeding. Quality assurance audit results at a large maternity hospital led to the development of a continuing education program to increase nurses' knowledge of breastfeeding and thereby reduce supplementation. An integrated quality assurance and research methodology was selected to analyze the impact of the education and yield results that would be more generalizable and interest a wider audience. Findings revealed no change in supplementation behavior occurred following a four-week education program. Only 33 percent of newborns in the study were unsupplemented during their hospital stay. Formula was the most often used supplement. Continuing education alone was not effective in changing behavior. As shown in the literature, post-course reinforcement of behavior needs to be built into the cost of the program to implement and sustain desired changes. PMID- 1418425 TI - Breastfeeding knowledge of hospital staff in rural maternity units in Ireland. AB - Knowledge of breastfeeding is necessary for health workers to adequately assist breastfeeding mothers. This paper examines the level of knowledge concerning breastfeeding in three rural maternity units in Ireland. Health workers responding to a self-report questionnaire felt that they had adequate knowledge, but their answers to the questions did not always bear this out. Health workers felt more staff training in breastfeeding would help to improve breastfeeding rates. Thirty-four percent of respondents had never attended continuing education on infant feeding topics. Manufacturers of artificial infant formula were the main source of continuing education information. The knowledge level of obstetricians did not appear to affect breastfeeding rates. Pediatricians' breastfeeding knowledge was good, but they had little input in the care of healthy babies. Rising breastfeeding rates were found in the unit where midwives were more recently qualified and had higher knowledge scores. The need exists for more breastfeeding education in all the units examined, ideally provided by a staff member with current lactation training. PMID- 1418426 TI - Nurses' knowledge of breastfeeding in a clinical setting. AB - Most obstetrical nurses subscribe to the "breast is best" theory. This project examined the current knowledge base of a sample of nurses and their practices relating to breastfeeding in three clinical settings. These study findings reveal that many nurses need to update their knowledge of those practices found to encourage successful breastfeeding. Only seven of 16 questions were answered correctly by more than 50 percent of the nurses surveyed. Areas of adequate knowledge included positioning, breastfeeding frequency, infant suckling patterns, and the importance of night feedings. Areas of inadequate knowledge included timing of the baby at the breast, milk production, use of glucose water, and the use of nipple shields. PMID- 1418427 TI - Interfeeding breast pain: a case report. PMID- 1418428 TI - Breastmilk oversupply despite retained placental fragment. AB - In clients experiencing oversupply, lactation consultants should question more closely the frequency of milk ejection reflexes and whether the mother is experiencing them only during breastfeeding or frequently, even while not nursing. If the mother is still experiencing vaginal bleeding, even if she is producing large quantities of milk, she should be encouraged to talk with her health care provider about having a sonogram in order to rule out the possibility of a retained placental fragment. PMID- 1418429 TI - Nipple pain related to vasospasm in the nipple? PMID- 1418430 TI - Breastfeeding by Federal Express. PMID- 1418431 TI - Antiinfectives in breastmilk. Part I: Penicillins and cephalosporins. PMID- 1418432 TI - Mother's own milk: guidelines for storage and handling. PMID- 1418433 TI - The glory of woman or love, marriage and maternity. 1896. PMID- 1418434 TI - Consensus statement from the consultation on HIV transmission and breastfeeding. PMID- 1418435 TI - WIC and breastfeeding: some background information and an invitation. PMID- 1418436 TI - Breastfeeding promotion in a rural Indiana WIC office. PMID- 1418437 TI - Surgical treatment of epilepsy. Proceedings of a Consensus Conference. March 19 21, 1990. PMID- 1418438 TI - Intractable complex partial seizure: correlation of magnetic resonance imaging with pathology and electroencephalography. AB - We prospectively analyzed MR studies of 32 patients with intractable complex partial seizures, who later underwent resection of EEG-proven seizure foci. Twenty-seven patients were imaged at 1.5, 4 at 0.35, and 1 at 0.5 Tesla. Correlation was obtained on all patients with EEG and surgical pathology. Of 19 patients with mesial temporal sclerosis (MTS), 13 exhibited an MR abnormality at the site of pathology as determined by EEG and surgery. Abnormalities included increased (8) or decreased (1) signal intensity, distortion of gray-white interface (1) and temporal lobe atrophy (3). Six patients had no abnormalities at the site of the diseased focus. MR was more sensitive in patients with other structural lesions which included tumor, encephalitis, polymicrogyria, cryptic vascular malformation, and tuberous sclerosis. Prior studies indicate some usefulness of MR in intractable seizure patients, but many report relative insensitivity of MR in defining an abnormality (as low as 11%). Our results demonstrate the usefulness of high-resolution thin-section multiplanar MR using cardiac gating or flow compensation techniques in this patient population. PMID- 1418439 TI - PET in relation to intracranial electrode evaluations. PMID- 1418441 TI - MRI, PET, SPECT: interrelations, technical limits, and unanswered questions. PMID- 1418440 TI - Single photon imaging computed tomography (SPECT) for localization of epileptogenic focus in patients with intractable complex partial seizures. AB - Interictal and ictal HIPDM-SPECT brain scans were obtained in 38 patients who eventually underwent temporal lobectomy for treatment of medically intractable complex partial seizures (CPS). Interictal studies revealed decreased regional cerebral perfusion (rCP) in the temporal lobe corresponding to the eventual site of surgery in 76% of the patients. Similarly, ictal studies demonstrated increased rCP in 91% of the patients. Of the 33 patients who had both interictal and ictal SPECT studies, 23 (70%) showed increased rCP in the ictal state and decreased rCP in the interictal state in the same temporal lobe which was subsequently removed. The SPECT scans were particularly helpful in providing confirmatory evidence for localization and in deciding to undertake temporal lobectomy in 16 patients whose EEG studies had provided less secure localization. Our experience suggests that interictal and ictal SPECT brain imaging can be easily obtained and provides reliable localizing information in the epileptic patients being considered for temporal lobectomy. PMID- 1418443 TI - Depth electrodes. PMID- 1418442 TI - Natural history of drug resistant seizures: clinical aspects. AB - In an effort to determine the long-term efficacy of surgical therapy for epilepsy, a control group of patients was identified. Both the surgically treated and non-surgical groups were evaluated before and after 5- or 10-year follow-ups for seizure frequency in the preceding 2 years. To date 39 patients have had bona fide partial seizures, with or without secondary generalization, and EEGs with focal epileptiform patterns. Prior to first evaluation, these patients had had seizures for an average of 10 years and were treated with an average of 54 AEDs with documented therapeutic serum levels in most; one-third of the patients participated in experimental studies. After treatment for another 5 years with an average of 2.5 AEDs or 10 years with an average of 4.0 AEDs, no one was seizure free. Fifteen percent had a 75% decrease in seizure frequency and 85% continued to have no significant improvement in seizure control. Thus despite vigorous treatment, these patients who might have been considered surgical candidates continued to have uncontrolled seizures. PMID- 1418445 TI - Strategies for focal resection in medically intractable epilepsy. PMID- 1418444 TI - Subdural electrodes in the presurgical evaluation for surgery of epilepsy. AB - This article gives first an overview of the advantages and disadvantages of electrodes of progressively greater invasiveness used in the evaluation of patients who are candidates for surgery of epilepsy. The following sections discuss the design of subdural electrodes, their clinical indications, and the relative advantages and disadvantages of subdural electrodes when compared with other invasive techniques. PMID- 1418446 TI - Different approaches to resective epilepsy surgery: standard and tailored. AB - Intra-operative approaches to resective surgery for medically intractable epilepsy, especially cases involving temporal lobes, vary from anatomically standardized operations to those tailored to the location of epileptogenic zones and eloquent areas in individual subjects. The choice of approaches seems to depend on different views of the variability in epileptogenic zones and eloquent areas and on the reliability of identifying these areas intraoperatively, including the value of interictal epileptic activity. Evidence relating to these issues is reviewed. Although the choice of an intra-operative approach has a major effect on the risks and costs of the evaluation for epilepsy surgery, with higher risks and costs for approaches using standard operations or extra operative recording, no controlled study has compared the approaches. Indeed, the reported outcome for optimal candidates for each approach is nearly identical, providing little justification for use of approaches with higher risks and costs in all patients. PMID- 1418447 TI - Temporal resections in the surgical treatment of epilepsy. AB - Cortico-amygdalo-hippocampectomy in our experience remains the surgical procedure of choice for the treatment of temporal lobe epilepsy. It allows removal of an ample amount of epileptogenic tissue, provides excellent exposure for the mesial structures and is not accompanied by significant intellectual deficit. It takes into account the fact that temporal seizures usually arise in the limbic structures but quickly recruit the whole anterior cortex in most instances. Selective amygdalo-hippocampectomy is an alternative approach when a clear mesiobasal limbic focus has been repeatedly demonstrated by intracranial recording. PMID- 1418448 TI - Clinical indications for hemispherectomy and callosotomy. PMID- 1418449 TI - Uncontrolled epilepsy in children. AB - Intractable seizures in any age indicates (1) the continued presence of an unacceptable quantity of seizures despite reasonable medical and social management or (2) seizure eradication at the expense of medication toxicity. The incidence of seizures deemed unacceptable depends on their nature, the patient's life-style, physiological and social consequences of uncontrolled seizures, and the promise of surgical alleviation. The true value of surgery should increase as candidates and surgical sites can be more accurately selected, the necessary (and unnecessary) diagnostic tests better identified, and all aspects of its effects objectively evaluated in follow-up. PMID- 1418450 TI - EEG selection for corpus callosotomy. PMID- 1418451 TI - Corpus callosotomy. PMID- 1418452 TI - Anatomical to functional hemispherectomy from Krynauw to Rasmussen. PMID- 1418454 TI - Methodological issues in outcome assessment. PMID- 1418453 TI - Assessment of surgical outcome. AB - Evaluation of outcome of epilepsy surgery is complex because of several factors. Epilepsy is itself a heterogeneous disorder. Different epilepsy centers encounter different referral mixes of patients. Institutions employ various methods for pre operative evaluation and widely varying surgical techniques. Clear definitions of surgical success and reliable scales for its measurement are lacking. Few data are acquired prospectively and maintained in a format allowing inter institutional collation of results. A better representation of surgical outcome could in the future be served by adherence to 4 principles: collection of common data in standard formats; comparison of like, rather than disparate, populations; maintenance of quantitative data in raw form; and measurement of outcome along several dimensions or scales. Psychosocial issues have been underemphasized in most prior analyses of outcome. PMID- 1418455 TI - Standards for epilepsy surgery centers. PMID- 1418456 TI - National Institutes of Health Consensus Development Conference Statement: surgery for epilepsy (19-21 March 1990). PMID- 1418457 TI - The natural history of drug resistant epilepsy: epidemiologic considerations. AB - Approximately 160,000 United States residents will be evaluated for newly identified unproved seizures in 1990. While the majority will have a favorable prognosis and more than 50% will ultimately be able to discontinue medication, about 10,000 will fall into the category 'intractable'. There are well established predictors for seizure remission and for successful withdrawal of medications, including seizure type, etiology, age at onset, neurologic status, and family history. There are few studies which have evaluated predictors for poor outcome, in part because of difficulties with definition. Predictors of poor outcome are not necessarily the converse of predictors of good outcome. Identification of such factors is important to allow earlier referral of patients destined to meet criteria for intractable to allow alternative therapies to be instituted. PMID- 1418458 TI - Drug treatment of uncontrolled seizures. AB - The success of AED therapy for epileptic seizures varies according to epilepsy and seizure type. The outcome is excellent in the idiopathic generalized epilepsies, poor in the secondary generalized epilepsies and intermediate for the partial epilepsies. For this latter group, a table of outcome is described in Table I. Overall, approximately 70% of patients can be reasonably managed using one AED, although several may need to be tried before considering monotherapy to be a failure. Of the 30% unsatisfactorily managed by monotherapy, approximately another one-third can be adequately managed given a combination of two drugs. Combinations of more than two drugs provide little if any additional benefit. Evidence that such combinations have efficacy is inferred from the observation of seizure exacerbation when one drug is removed purposely to elicit seizures during evaluation for possible epilepsy surgery. The remaining patients are often considered for trial of an investigational drug although prospects for important improvement are very small even with use of agents shown to be effective and introduced for treatment of epilepsy. Thus, 15% of patients may conservatively be considered for surgical therapy. This would not suggest that all such patients are appropriate candidates from other aspects, but at least they can be considered to have failed all reasonable drug therapy. PMID- 1418459 TI - Present status in the treatment of the epilepsies. PMID- 1418460 TI - Clinical and CCTV-EEG evaluation in presurgical work-up of temporal and frontal lobe epilepsies. PMID- 1418461 TI - Presurgical EEG investigation in frontal lobe epilepsy. AB - Poor localization of the interictal epileptic abnormality and the rather unreliable EEG localization of ictal onsets in patients with frontal lobe epilepsy may be due to some of the following factors: (1) high risk of EEG sampling error, (2) early seizure spread within and outside the frontal lobe, (3) widespread distribution of the epileptogenic brain tissue responsible for the patient's habitual seizures, and (4) secondary bilateral synchrony and secondary epileptogenesis. The relevance of these factors in the preoperative investigation of patients with frontal lobe epilepsy was studied in: (a) 34 adult patients (mean age: 25 years) who became and persisted seizure free after restrictive surgical removal of the anterofrontal region, the parasagittal region convexity or the fronto-opercular area; (b) 12 patients in whom the pre-operative EEG investigation with extracranial electrodes failed to localize the site of seizure onset, leading to further investigation with depth electrodes. PMID- 1418462 TI - Intractable epilepsy in adults. AB - Intractable epilepsy can be defined as seizures which have not been completely controlled with AEDs 1 year after onset despite accurate diagnosis and carefully monitored treatment. Once intractable, there is a low probability of remission. Predictors of intractability include the presence of partial seizures, structural abnormalities on imaging studies, and abnormalities on the neurological examinations. If a person continues to have seizures in spite of adequate treatment with AEDs, surgical options should be considered. PMID- 1418463 TI - Use of psychological and neuropsychological variables in selection of patients for epilepsy surgery. AB - Cortical resection surgery for epilepsy is costly, involves risk, and does not result in significant seizure relief in a number of patients. Therefore, it is important to develop methods which will as accurately as possible identify in advance those persons who will or will not be helped by this procedure. From a review of the literature and from a presentation of original data, it is concluded that psychological/neuropsychological variables are valid predictors of cessation of seizures following surgery but that they are only infrequently used. A multidisciplinary, multivariate statistical approach, using EEG findings and psychological/neuropsychological variables in combination, provides the most accurate predictions which are superior to those derived from using either EEG variables or psychological/neuropsychological variables alone. This approach also avoids much of the predictive instability encountered when single variables are evaluated. Since psychological/neuropsychological variables are obtained at low cost and are non-invasive, further evaluation of their role as predictors of seizure relief following surgery is needed. PMID- 1418464 TI - Role of the neuropsychological evaluation and the intracarotid sodium amobarbital procedure in the surgical treatment for epilepsy. PMID- 1418465 TI - Neuropsychological techniques in the identification of epileptic foci. AB - Neuropsychological evaluation contributes towards identification of a seizure focus through assessment of function. Tests sample widely among cognitive abilities, usually contrasting language and visuospatial competence. In patients with a temporal-lobe focus, evaluation of memory is crucial and ideally should comprise a variety of tasks tapping different aspects of learning and memory. As a means of predicting and preventing severe postoperative memory impairment, memory is further tested in many cases with the intracarotid sodium amytal (IAP) procedure; hippocampus will be spared in patients who fail IAP memory tests. Performance after temporal lobectomy on three basic memory tests was evaluated in patients who had failed pre-operative IAP memory tests compared to those who had passed. Those who had failed performed significantly worse, confirming fragility of memory function in cases who have been identified as at risk by the IAP procedure. PMID- 1418466 TI - Identification of the epileptic focus: magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) is the most sensitive and specific structural imaging technique available to demonstrate focal epileptogenic lesions in patients with intractable partial epilepsy. MRI may be useful in the selection of candidates for surgical treatment of epilepsy. The studies may also assist in the implantation of depth electrodes and in the stereotactic resection of epileptogenic lesions. More recent applications of this neuroimaging modality in the surgical treatment of epilepsy include pre-operative hippocampal formation of volume measurements and postoperative quantitative determinations of cortical resections. PMID- 1418467 TI - Benign epilepsy of childhood with occipital paroxysms. PMID- 1418468 TI - The electrical status epilepticus syndrome. AB - The authors review the clinical and electroencephalographic features of electrical status epilepticus during slow sleep (ESES) in children. The major points of debate regard the nosology and diagnosis of ESES. The relationship between ESES and the neuropsychological impairment is emphasized. It is concluded that ESES is a separate electro-clinical entity which deserves individual categorization. PMID- 1418469 TI - Further genetic aspects in benign localized epilepsies in early childhood. PMID- 1418470 TI - Sleep organization in benign childhood partial epilepsies. PMID- 1418471 TI - Sixth-month benign familial convulsions. PMID- 1418472 TI - Genetically determined epileptic seizures in animals. PMID- 1418473 TI - Benign myoclonic epilepsy of infancy: electroclinical symptomatology and differential diagnosis from the other types of generalized epilepsy of infancy. AB - Benign myoclonic epilepsy in infancy (BME) is characterized by the occurrence of brief myoclonic attacks in normal infants aged 4 months to 3 years. There is no prior personal history, although in some patients 1 or 2 isolated febrile convulsions may occur prior to the onset of myoclonias. A family history of epilepsy or febrile convulsions is present in 30% of cases. Myoclonic attacks are short and mild, they involve mainly the head and upper limbs. The psychomotor development continues normally after the onset of seizures. The EEG shows a normal background activity and generalized spike-wave or polyspike-wave discharges associated with the myoclonias. These abnormalities are activated by drowsiness and during the first stages of sleep. A clinical and EEG photosensitivity is present in one-third of the patients. Myoclonias can be easily controlled by valproate monotherapy. Rare grand mal seizures can occur during adolescence, after withdrawal of drug treatment. The psychomotor evolution is good if treatment is started early. When myoclonias begin during the first year of life, the diagnoses of cryptogenic infantile spasms and of non-epileptic benign infantile myoclonus must be eliminated. In cases with a later onset, the following diagnoses can usually be easily discarded: cryptogenic Lennox-Gastaut syndrome, myoclonic-astatic epilepsy and unclassified epilepsies with the association of myoclonias and other types of seizures. PMID- 1418474 TI - The therapy of benign myoclonic epilepsy in infants. AB - The authors report the results of treatment of 14 patients (10 male, 4 female, average age 20.3 years) with benign myoclonic epilepsy. Valproate monotherapy led to control of seizures in 10 cases, and to a distinct reduction of seizure frequency in 3 cases. Thrombocytopenia was the only side-effect encountered in this study. PMID- 1418475 TI - Does an idiopathic west syndrome exist? PMID- 1418476 TI - Symptomatology and electroencephalography of the 'genuine' type of the West syndrome and its differential diagnosis from the other benign generalized epilepsies of infancy. PMID- 1418477 TI - The EEG in benign generalised epilepsies in infancy and the differential diagnosis from other generalised epilepsies. PMID- 1418478 TI - The prognosis of benign generalized epilepsies in early childhood. PMID- 1418479 TI - Myoclonic-astatic epilepsy. AB - Myoclonic-astatic epilepsy (MAE) belongs to the group of epilepsies with primarily generalized seizures as absence epilepsies, and juvenile myoclonic epilepsy, as well as infantile and juvenile idiopathic epilepsy with generalized tonic-clonic seizures. Like these types of epilepsy, MAE is polygenically determined with little non-genetic variability. The disease is characterized by the following criteria: genetic predisposition (high incidence of seizures and/or genetic EEG patterns in relatives); mostly normal development and no neurological deficits before onset; primarily generalized myoclonic, astatic or myoclonic astatic seizures, short absences and mostly generalized tonic-clonic seizures; no tonic seizures or tonic drop attacks during daytime (except for some rare cases with a most unfavourable course); generalized EEG patterns (spikes and waves, photosensitivity, 4-7/sec rhythms), no multifocal EEG abnormalities (but often pseudofoci). There is a partial overlap with other 'syndromes', such as benign and severe myoclonic epilepsy in infants (Dravet et al., 1985a, b), myoclonic epilepsy of infancy and early childhood (Aicardi and others). In differential diagnosis the Lennox-Gastaut syndrome in its stricter sense has to be considered, and also atypical benign partial epilepsy or pseudo-Lennox syndrome. Discussion is presented of possible pitfalls in the classical syndromic approach to classifying epilepsies of early childhood, and of the advantages of a neurobiological view for understanding the immense variability of clinical manifestations of epilepsy. PMID- 1418480 TI - Clinical differential diagnosis between benign and malignant epileptic syndromes with generalized seizures in early childhood. PMID- 1418481 TI - Behavioural and developmental aspects of primary generalized myoclonic-astatic epilepsy. AB - The evolution of psychomotor development and behaviour was studied in 15 children with primary generalized myoclonic-astatic epilepsy and with developmental status adequate for age at final examination at school age following a mean follow-up period of 8.5 years. Temporary arrest of mental and motor development in 4 children was related to high seizure frequency or, in 3, to non-convulsive status. Different types of behavioural abnormalities were documented frequently during the course of the disorder; they were significantly related to active seizure periods and to a lesser extent to anticonvulsant medication. Persistent behavioural abnormalities were noted in 5 children. Hyperkinesia, short attention span and emotional lability were the most frequent complaints. None of the children needed special care and those followed-up until school age were seizure free, without medication and in classes appropriate for their age. At initial examination the high probability of a favourable prognosis may be anticipated in children with normal development before seizure onset, lack of gross brain pathology and with strong indications (family history and/or EEG criteria) for a genetic predisposition. Nevertheless, repeated systematic re-evaluation for early recognition of possible developmental and/or behavioural deviances throughout the course of illness are recommended. PMID- 1418482 TI - Clinical and electroencephalographic symptomatology of the 'genuine' Lennox Gastaut syndrome and its differentiation from other forms of epilepsy of early childhood. PMID- 1418483 TI - Sleep architecture and childhood absence epilepsy. PMID- 1418484 TI - Comparison of the EEG background activity of epileptic children and children with migraine. AB - The EEG background activity was investigated in the interictal EEGs of 19 children with migraine and of 88 patients with epilepsy of idiopathic origin in the third year of treatment. The control group consisted of 96 healthy children matched for age. Spectral analysis was performed, and parameters of the relative power within the conventional frequency bands were compared with norm data. The means of parameters representing the background activity of migraine as well as of epileptic patients significantly differed (slowing) from those of healthy controls. No significant differences were found between the main groups of migraine and epileptic patients. In comparing the subgroups of epileptic as well as of migraine patients, the composition of the background activity in migraine patients without aura differed the least from the controls. While the background activity in epileptics (especially those with an unfavourable course) showed a moderate slowing, a high degree of slowing was observed in patients with migraine accompagnee. PMID- 1418485 TI - Migraine and epilepsy, with special reference to the benign epilepsies of childhood. PMID- 1418486 TI - International symposium on benign partial and generalized epilepsies of childhood. Summation. PMID- 1418487 TI - Benign localized epilepsies in childhood: historical aspects. PMID- 1418488 TI - Rolandic epilepsy: clinical and electroencephalographic features. AB - Benign rolandic epilepsy (BRE) is a common seizure disorder confined solely to children. The disorder is marked clinically by nocturnal generalized tonic-clonic seizures and diurnal seizures consisting of simple partial seizures consisting of brief unilateral facial clonic activity, dysphasia, and drooling. The EEG abnormalities are unique, consisting of generally high amplitude, centrotemporal spikes that are activated by sleep. The seizures typically begin in the first decade and almost always stop by age 16 years. The seizures are usually infrequent although clusters of seizures do occur. When the physician elects to treat, the seizures are usually easily controlled. PMID- 1418489 TI - Classification of epileptic seizures and the epilepsies: an overview. PMID- 1418490 TI - The neurophysiological features of benign partial epilepsy with rolandic spikes. AB - SEPs were performed in 44 children with benign partial epilepsy with rolandic spikes (BERS). High-amplitude mid- or long-latency SEPs were recorded in 17 patients (38%). These giant responses showed normal latency values but reached an exceedingly high amplitude (up to 200 microV). They showed the same reactivity characteristic of normal long-latency SEPs. In a 3-year follow-up study, the giant responses were shown to disappear in some patients and to shift from side to side in others. Our study demonstrates that giant SEPs are relatively common in BERS and give further support to the concept of a functional nature of rolandic foci. PMID- 1418491 TI - Contribution to the genetics of rolandic epilepsy: waking and sleep EEGs in siblings. AB - Waking and sleep EEGs were recorded in 69 siblings of 43 patients with rolandic spikes. 36 suffered from rolandic epilepsy, 7 from other diseases or symptoms (headaches, migraine, learning problems). At least one sibling with epileptic activity was found in 51.16% of the patients. Taking the 69 siblings as a basis, in 26 (37.68%) epileptic activity was recorded. Benign spike foci were recorded in only 4 siblings, generalized spike-wave complexes were seen in 22. Most epileptic activity was recorded in the age group of 5-12 years (54.3%). Nearly one-half (17.4%) was recorded exclusively in sleep, predominantly in sleep stage C (88%). Siblings of patients with (40%) and without seizures (37.5%) showed approximately the same rate, likewise siblings with (40%) and without seizures (34.8%). An autosomal-dominant mode of inheritance is assumed, but a multifactorial mode is also discussed. PMID- 1418492 TI - Benign rolandic epilepsy of childhood: topographic EEG analysis. AB - Topographic EEG investigation with instant voltage mapping showed maximal negativity of 'rolandic' spikes over central or midtemporal electrodes with spread to parietal or upper frontal areas, and a dipole distribution (centrotemporal negativity, frontal positivity). There was no correlation of spike amplitude or duration with spread to adjacent areas. No other focal abnormalities, such as focal slowing, occurred. Spike activity was pronounced during light sleep and was often associated with generalized spike-wave activity, and thus was a sign of functional disturbance rather than the sequelae of brain damage. A review of the literature indicates that this pattern is helpful in differentiating this from focal abnormalities due to brain lesions. PMID- 1418493 TI - Is rolandic discharge a hallmark of benign partial epilepsy of childhood? AB - A longitudinal study was conducted in 89 children with partial seizures who had rolandic discharges on their interictal EEGs. The clinical characteristics and seizure prognosis were compared in children without an organic background (idiopathic) and in children with an organic background (symptomatic). Since rolandic discharges and sylvian seizures were found in the symptomatic children and their seizure outcome was favorable, it is likely that they are symptomatologically close to benign childhood epilepsy with centrotemporal spikes. Some of the symptomatic patients may have had complex partial seizures, although rolandic discharges were the principal EEG finding. Their seizure prognosis was as unfavorable as that of the patients with other symptomatic partial epilepsies. The rolandic discharges disappear in an age-related manner in idiopathic patients, but tend to persist in the symptomatic ones. The presence of rolandic discharges was not considered a hallmark of a benign outcome. Instead, the presence of sylvian seizures heralds a benign outcome of partial epilepsies regardless of whether they are idiopathic or symptomatic. PMID- 1418494 TI - Rolandic spikes and cognitive function. PMID- 1418495 TI - The prognosis of benign localized epilepsy in early childhood. AB - Onset of seizures during early childhood is a not infrequent possibility in benign partial (localization-related) epilepsy (BPEC) when all these syndromes and not only benign partial epilepsy with centrotemporal spikes are considered. In patients followed up for long periods of time, temporal changes in the EEG often make impossible a distribution into discrete syndromes. The electroclinical patterns overlap and the determining factor is not the location but the morphology of the sharp waves. A complete remission is observed in all patients, with rolandic and/or extrarolandic foci. In rare patients, seizures occur during adolescence or later and an early onset is a possible risk factor for such an outcome. It is not a relapse of BPEC but another epileptic syndrome, usually a generalized idiopathic epilepsy. BPEC may be considered as a risk factor for late epilepsy. Patients with an early onset of BPEC tend to have a longer active period of epilepsy and a higher total number of seizures, whatever is the EEG pattern. But neither frequent seizures nor a long seizure period impair the children's abilities. Nonetheless, when BPEC begins in early childhood, the patient is prone to experience frequent seizures during several years. Drug therapy is advisable more often than in BPEC with a later onset. PMID- 1418496 TI - The value of the EEG in the diagnosis of localized epilepsies in children. PMID- 1418497 TI - BECT: comparison of cerebral blood flow imaging, neuropsychological testing and long-term EEG findings. PMID- 1418498 TI - Focal epileptic EEG discharges in children not suffering from clinical epilepsy. PMID- 1418499 TI - Pharmacological profile of novel cyclic analogs of 2-amino-7-phosphonoheptanoic acid. PMID- 1418500 TI - Effect of intranigral muscimol on animal models of generalized absence seizures. PMID- 1418502 TI - Environmental conditions for treatment of burned patients by the exposure method. AB - The influence of the thermal environment on evaporation and heat loss from patients with severe burns treated by exposure has been studied. Simple heat transfer equations can be used to predict changes resulting from alterations in environmental conditions and these have been tested using phantoms. The method relies upon the derivation of surface diffusion resistances to describe the moisture properties of burn wounds. Clinical measurements revealed wide variations in evaporation rates and diffusion resistances for different wounds. Evaporation rates changed by less than 30 per cent during the first 5-6 days following injury, after which evaporation from partial skin thickness wounds gradually fell whereas that from full skin thickness wounds tended to remain higher. Raising ambient temperature can compensate for increased evaporation heat losses. Patients can be treated at ambient temperatures of 32-35 degrees C in the intensive care room with a specially designed airflow system. However, raising the temperatures of standard wards with no special airflow or temperature control facilities often caused patients to sweat, further increasing heat loss. PMID- 1418501 TI - Profile of the paediatric burn patient in a Canadian burn centre. AB - Five hundred and eighty-three children (0-18 years old), consisting of 33.4 per cent of all burn inpatients, were admitted to the University of Alberta Hospitals over an 11-year period (January 1978 to December 1988). Demographic and outcome variables, in addition to aetiological factors, were examined. 48.4 per cent of burns occurred in children less than 4 years of age, with males predominating in every age group (P less than 0.001). Children had smaller burns, a higher incidence of scalds, less inhalation injuries and a lower mortality compared to adult burn patients admitted over the same time period (P less than 0.05). There was a low incidence of confirmed child abuse by burns (1.4 per cent). High-risk environments identified were the home (74.6 per cent of burns) and recreational settings (12.4 per cent of burns), mainly occurring around campfires. Native children were overrepresented in the burn population compared to the general population by a factor of approximately 10:1. Scald prevention, high-risk environments (home and recreational), high-risk populations (male and natives) and unsafe practices with flammable liquids (petrol in particular) should be emphasized in paediatric burn prevention programmes. PMID- 1418503 TI - Metabolic abnormalities of mitochondrial redox potential in postburn multiple system organ failure. AB - Forty-five burn patients underwent sequential assays for plasma acetoacetate and beta-hydroxybutyrate concentrations as well as plasma amino acid levels. Those patients who went on to develop multiple system organ failure were noted to have a decrease in their acetoacetate concentration with time, whereas there was no change in those patients who failed to develop multiple system organ failure. The plasma concentration of beta-hydroxybutyrate was not altered by multiple system organ failure. In addition, the plasma acetoacetate/beta-hydroxybutyrate ratio was found to be directly related to the plasma concentration of branched chain amino acids and inversely related to the concentration of aromatic amino acids. PMID- 1418504 TI - Looking at burn wounds: the A. B. Wallace Memorial Lecture 1991. PMID- 1418505 TI - Survival in major burn injuries treated by one bathing in cerium nitrate. AB - Sixty-four patients aged 16-74 years with total body surface area burns (TBSA) ranging from 30 to 90 per cent, were given one bathing in 0.04 M cerium nitrate within 4 h of admission to hospital. Of 21 patients aged 16-30 years, one died (aged 28 with 90 per cent TBSA), and of those aged 31-74 years, two died, one (aged 50 years with 55 per cent TBSA) had multiple internal injuries, the other (aged 51 years with 55 per cent TBSA) had a pulmonary embolism at day 19. Two risk scores, developed from data on 11,200 burn patients treated by standard methods (Roi et al. 1983), were applied to the analysis of risk for 59 patients for whom both total burn surface (TB) and full thickness (FT) areas had been recorded. About 20 patients bore risk of 0.8 or greater on the FT scale and 1.0 on the TB scale, yet instead of 80 per cent deaths among these, only two died. No FT assessment had been made on the multiple injury death whose TB risk score was 0.66. Such survival results in high-risk patients should encourage the use of cerium nitrate for treating serious burn injury. PMID- 1418506 TI - The progress of hypertrophic scars monitored by ultrasound measurements of thickness. AB - Ultrasound scanning was used to measure the thickness of hypertrophic scars following burn injury. Scarred areas on patients receiving pressure therapy were monitored at regular intervals from the initial healing, through the hypertrophic stage, to maturation of the scars. The data, collected over a period of 30 months, allowed a comparison of scar development in children and adults and a comparison of the response at different anatomical sites. Measurements made on individual patients could be related to factors affecting the progress of their hypertrophic areas and provided a useful backup to visual assessment during pressure garment therapy. PMID- 1418508 TI - Management of thermal injury in pregnancy--an analysis of 16 patients. AB - Sixteen patients at various stages of pregnancy suffered burns covering between 10 and 80 per cent of the body surface area. This review highlights the management problems of these patients during the first, second and third trimesters. Only two mothers (both with 80 per cent TBSA burns) died. There were five fetal deaths, three of them intrauterine. PMID- 1418507 TI - DuoDERM hydroactive dressing versus silver sulphadiazine/Bactigras in the emergency treatment of partial skin thickness burns. AB - The study compared DuoDERM Burn Pack Hydroactive Dressings (DHD) with silver sulphadiazine/Bactigras dressings (SSD/Bactigras) in the outpatient management of small partial skin thickness burns. Forty-eight patients were entered into the study, and randomly allocated into either the DHD or SSD/Bactigras group. Burn wounds were followed until complete re-epithelialization occurred. There were no statistical differences between the groups, either with respect to their composition or characteristics of healing in days, and patients' subjective responses to treatment. However, application was easier in the DHD group (93 per cent), compared with 71 per cent in the SSD/Bactigras group (P = 0.0009), and the SSD/Bactigras were easier to remove (96 per cent) versus DHD (66 per cent, P = 0.0004). Furthermore, the DHD group had significantly less dressing changes; a mean of three changes per subject in the DHD group compared with eight in the SSD/Bactigras group (P = 0.117). Two burn wounds became infected in the DHD group, and one in the SSD/Bactigras group. In this study both modalities were found to be equally suitable and effective for small partial skin thickness burns. PMID- 1418509 TI - Microskin autograft with pigskin xenograft overlay: a preliminary report of studies on patients. AB - Split-thickness pigskin graft (STPSG) was used to replace allograft skin for microskin grafting in 16 patients, nine of whom were burn patients, five suffered from traumatic defects and two from diabetic ulcers. The expansion ratios used in these patients ranged from 8:1 to 12:1. The STPSG preparation described was found to be safe for clinical application. The autogenous donor skin was excised from the inguinal area, and the donor site was primarily closed. There were no instances of donor site morbidity. The majority of the STPSG overlays adhered to the wound firmly. Histological examination showed that the microskin grafts proliferated actively immediately beneath the STPSG overlay. The time for the wound to be fully resurfaced varied from 13 to 21 days depending on the expansion ratio employed. There were only two episodes of pseudomonas infection and no further grafting was required in any of the patients. In this study the pigskin xenograft was found to provide a suitable environment for the epithelialization of microskin autografts. When allograft is not available, this is an alternative way of ensuring successful microskin grafting. PMID- 1418510 TI - X-plasty for repair of burn contractures. AB - Release of skin contractures across a joint surface by X-incision is presented. The method is particularly suitable for severe and moderate contractures. Resultant long lateral flaps lead to good coverage of the flexor surface of the joint. This prevents recurrence of contracture even in growing children. The method is suitable for any joint. PMID- 1418511 TI - Burns following cigarette lighter fluid abuse. AB - Seven patients with burns associated with butane cigarette lighter fluid abuse, in a group setting within an enclosed space, are presented. In all patients there was a reluctance to admit that butane vapour was in use as an intoxicant immediately prior to the injury. It is obvious from the circumstances of these injuries that the hazardous nature of cigarette lighter fluid is not fully appreciated. Since the resultant injuries are usually minor (all patients recovered spontaneously with conservative management, the hospital stay averaging 2 days), it is probable that many more occur, but do not present to accident departments as the victims are wary of repercussions should they admit to intoxicant vapour abuse. In view of the medical sequelae that can follow butane inhalation, burns unit staff should be aware of the problems, their recognition and treatment. PMID- 1418512 TI - Predominance of staphylococcal organisms in infections occurring in a burns intensive care unit. AB - To assess the sites, incidence, and bacteriology of infections in intensive care burn patients, a prospective survey of all admissions to a tertiary care institution burn unit was carried out over a 12-month period. One hundred and sixteen patients were admitted, 106 with a diagnosis of thermal burns. Forty patients developed 90 infections. Only two deaths occurred, one in a patient with sepsis. In order of frequency, pneumonia, burn infection, UTI and primary bacteraemia were most common. Staphylococcal species accounted for a majority of infections at all body sites except UTI (47 per cent of all infections, including 11 of 14 bacteraemic infections). Staph. aureus sepsis was more common in those carrying the organism on admission. Strain typing of paired admission and subsequent clinical isolates in 19 patients with Staph. aureus sepsis indicated that eight (42 per cent) became infected with a strain they carried on admission. Further reductions in septic complications of burns in our center would be best directed at staphylococcal species, particularly Staph. aureus. Both eradication of carrier state, and prevention of acquisition of Staph. aureus strains could be explored. PMID- 1418513 TI - Primary pressure grafts in early reconstruction of deep facial burns. AB - The face is an area of great cosmetic importance where the repair of deep burns is particularly delicate, as both appearance and function must be taken into account. In order to improve the aesthetic prognosis of full skin thickness facial burns, a primary pressure graft technique was used in eight patients. Early excision was carried out during postburn day 3 and after good-quality granulation tissue was obtained around day 10, a full skin thickness graft was applied. Pressure was applied to the graft and maintained for 10 days. The grafts took successfully in all patients with very satisfactory cosmetic results. This is an original technique as it replaces burned tissue at a very early stage with tissue which is normal in thickness and quality. PMID- 1418514 TI - Phosphorous pentachloride chemical burn--a slowly healing injury. AB - A 51-year-old chemical engineer sustained phosphorous pentachloride partial skin thickness burns over 20 per cent of his body surface area. Although macroscopically and microscopically the wound seemed to be superficial, the course of clinical healing of this injury was very slow and painful. Retrospectively this burn should have been treated by early excision and grafting. PMID- 1418516 TI - Development of the treatment of partial skin thickness burns since the Second World War: an overview. PMID- 1418515 TI - Bilateral metastatic endophthalmitis as a complication of major burns. AB - Metastatic infection of the eye is a rare complication of burns. The following report describes a patient with endophthalmitis occurring as a complication of major burns. The diagnostic difficulties that arose are discussed and the recommended treatment outlined. PMID- 1418517 TI - Treatment of burns with occlusive dressings: some pathophysiological and quality of life aspects. PMID- 1418519 TI - Burn bacteriology during the last 50 years. PMID- 1418520 TI - Preface: organizational aspects of burn care in The Netherlands and some aspects of future burn care. PMID- 1418518 TI - Historical appraisal of the use of skin allografts in the treatment of extensive full skin thickness burns at the Red Cross Hospital Burns Centre, Beverwijk, The Netherlands. PMID- 1418521 TI - Then and now: 50 years of burn treatment. PMID- 1418522 TI - [Determination of the active constituent in Veronicastrum sibiricum (L.) Pennell]. AB - The anti-inflammatory and analgesic constituent isoferulic acid was quantitatively analyzed by means of TLC-SM. The content is 0.09%. PMID- 1418523 TI - [Kinetics of pharmacologic effects of radix Aconiti Lateralis Preparata and sini decoction]. AB - In the study of analgesic action of Radix Aconiti Lateralis Preparata and Sini Decoction hot-plate method was used and the time-effect relationship was determined. The biological half-lives were 11.05 h and 6.84 h respectively. In the study of the effect on inflammation induced by egg white in the ankle joints of rats, the method of complement ED50 was used. The residual rates of the dosages after an interval of 6 hours were 0.60 and 0.69, and the biological half lives were 8.11 h and 11.35 h respectively. PMID- 1418524 TI - [Inhibitory effects of the extract of pilose antler on monoamine oxidase in aged mice]. AB - It was demonstrated that the water extract of Pilose Antler (WEPA) showed a higher inhibitory effect on MAO-B activities in the liver and brain tissues of aged mice, but nearly no effect on NAO-A. WEPA could significantly increase the contents of 5-HT, NE and DA in the brain tissues of aged mice. In vitro experiments revealed that the inhibition of WEPA on MAO-B was competitive, but on MAO-A was of mixed-type. PMID- 1418526 TI - [Review of improving the technology of processing Chinese herbal medicines]. AB - In this paper, the present situation of processing technology for Chinese herbal medicines is expounded in all aspects. Careful processing, overall developing and comprehensive utilization are put forward as improving ways, in the hope of providing a scientific basis for carrying forward the traditional processing techniques for Chinese herbal medicines in producing areas and putting the resources to full and rational use. PMID- 1418525 TI - [Effects of ginseng volatile oil on cytochemical components of SGC-823 gastric carcinoma in cell culture]. AB - After 24, 48 and 72 hours' treatment of cells of SGC-823 gastric carcinoma in cell cultures with ginseng volatile oil, glycogen, succinate dehydrogenase and DNA in single cells were measured quantitatively with MPV2 microscope photometer. The results show that the inhibition of cancer cell growth by ginseng volatile oil may be due to the action of metabolism of DNA, carbohydrates and energy. PMID- 1418527 TI - [Discussion on criteria for appraising the endanger threatening rare medicinal plants]. AB - This paper deals with the criteria for appraising the endanger threatening rare medicinal plants. A preliminary evaluating method is presented. PMID- 1418528 TI - [Production layout of endemic and superior Chinese medicinal materials in Sichuan]. AB - In this paper, the climatic ecological adaptabilities of 15 kinds of genuine Chinese medicinal materials in Sichuan are quantitatively illustrated by means of Fuzzy sets and some tentative ideas about their rational production layout are advanced for the first time. PMID- 1418529 TI - [Scanning electron microscopic identification of hairs on surface of fruits and seeds of Chinese medicinal plants]. AB - A comparative identification of hairs on surfaces of fruits and seeds of some Chinese medicines has been made, and a key to 13 kinds of hairs has been compiled. According to the characters of hairs, it is possible to identify some Chinese drugs in powder form. PMID- 1418530 TI - [Effect of moisture and temperature on seed viability of Fritillaria thunbergii Miq]. AB - This paper deals with the effect of two moisture levels (9.2%, 16.7%) and three temperature levels (15, 25, 35 degrees C) on seed viability of Fritillaria thunbergii. The results show that moisture and temperature have significant effects on seed viability. PMID- 1418531 TI - [Determination of sugar components in wild and cultured sclerotia of Grifola umbellata (pers. ex Fr.) Pilat at different ages]. AB - Our determination indicates that in both wild and cultured sclerotia of Grifola umbellata the contents of reducing sugar decrease with the growing years; the contents of Polysaccharide peak in the second year of growth; the contents of protein increase with the growing years; the contents of fat reaches maximum in the first year of growth; in cultured sclerotia ergosterol becomes highest in contents when the plant is two years old, while in wild sclerotia it remains lowest. PMID- 1418532 TI - [Volatile oil in Ephedra sinica Stapf. and its processed products by GC-MS]. AB - This paper deals with the changes in contents and chemical composition in the volatile oil of Ephedra sinica before and after processing. The results indicate that after processing, the more the substances of low boiling point, the higher their contents and vice versa. The changes are particularly obvious in yellow fried Ephedra sinica. PMID- 1418533 TI - [Saponins in fruits pedicels of Panax notoginseng (Burk.). F.H. Chen]. AB - Six saponins were isolated from the fruit pedicels of Panax notoginseng for the first time. They were identified as ginsenoside-Rc, -Rb3, -Re, notoginsenoside Fe, -R1 and gypenoside IX by chemical and spectroscopic analysis. PMID- 1418534 TI - [Isolation and identification of chemical constituents from Hedyotis chrysotricha (Palib.) Merr]. PMID- 1418535 TI - [Evaluation of rare and endangered conservational medicinal plants in Jiangsu Province]. PMID- 1418536 TI - [Pharmacognostical study on the Chinese drug gualouzi]. AB - The Chinese drug gualouzi is taken from a variety of plants. In this paper, 22 kinds of gualouzi derived from 22 plants of Trichosanthes have been studied in their pharmacognostical characters and microproperties and accordingly divided into four types. Two keys are compiled based on the experimental results. PMID- 1418537 TI - [Stability of shuang huanglian aerosol]. AB - The contents of chlorogenic acid and baicalin in shuang huanglian aerosol were determined by HPLC. The process of chemical kinetics of the aerosol was studied by constant temperature acceleration tests, and the stability of the drug predicted. The results appeared close to those from the stored sample method. pH changes during degradation of the drug were also observed. PMID- 1418538 TI - [Constituents of essential oils from leaves, stems, and fruits of Perilla frutescens (L.) Britt]. AB - The constituents of essential oils obtained from the leaves, stems, and fruits of Perilla frutescens were analysed by GC-MS. 65 compounds including perilla aldehyde, perilla alcohol, trans-caryophyllene and hexadecanoic acid, etc. were identified. Their percentages in the oils were given. PMID- 1418539 TI - [GC-MS analysis of essential oils in needles of Pinus in northeastern China]. AB - The essential oils of five species of Pinus (P. densiflora, P. sylvestris var. mongolica, P. sylvestris var. sylvestriformis, P. tabulaeformis and P. takahasii) have been analysed by GC-MS. Fifty compounds have been identified. PMID- 1418540 TI - [Ca2+ channel blocking effect of panaxadiol saponins and panaxatriol saponins of cultured cardiac cells]. AB - It was found that PDS and PTS decreased the action potential parameters of the cultured myocardiocytes in a dosage-dependent way. The effects of PDS 1000 micrograms/ml, PTS 200 micrograms/ml were in correspondence with the known Ca2+ channel blocker Mn2+ 0.05 micrograms/ml. Washing out, administration of epinephrine 10 micrograms/ml or Ca2+ 80 micrograms/ml were able to reverse the action potential from inhibition. The above results indicate that both PDS and PTS have Ca2+ channel blockade action. PMID- 1418541 TI - [Effect of radix Astragali and radix ginseng in enhancing the metabolism of human myocardial cells in vitro]. AB - Our experiment indicated that in Radix Astragali and Radix Ginseng treated human myocardial cell cultures the level of LDH and SDH elevated in varying degrees and in Radix Ginseng treated cells the cAMP showed higher levels but in Radix Ginseng treated ones the same was not observed. This suggests that the metabolism of myocardial cells is enhanced by Radix Astragali or Radix Ginseng. PMID- 1418543 TI - [Compatibility of Chinese drugs radix Aconiti carmichaeli with rhizoma Pinelliae]. AB - To find out whether the Chinese drug Radix Aconiti Carmichaeli is compatible with another Chinese drug Rhizoma Pinelliae in preparation, the two medicinal herbs were made into different forms of decoctions. Experiments with these decoctions were carried out to observe the action on isolated hearts of toads and the ECG and acute toxicity on mice. The results showed that in terms of toxicity there was no marked increase in the mixed decoction as compared with the other two decoctions prepared from Radix Aconiti Carmichaeli and Rhizoma Pinelliae separately. PMID- 1418542 TI - [Effect of sodium 18 beta-glycyrrhetate on experimental arrhythmia]. AB - The effect of sodium 18 beta-glycyrrhetate (SGA) on experimental arrhythmia was investigated. The result shows that SGA strongly counteracts arrhythmia induced by chloroform of chloroform adrenaline, lengthens the appearance time of arrhythmia induced by CaCl2, slightly retards the heart rate of rats and rabbits, and partly antagonizes the acceleration effect of isoproterenol on rabbit hearts. PMID- 1418544 TI - [A review on the chemical constituents of Annona plants]. AB - The paper reviews the progress in the research on Annona plants, including the structure of chemical constituents, spectroscopic characteristics and physiological activities. A new kind of anticancer constituent is also introduced. PMID- 1418545 TI - [Pharmacognostical studies on the Chinese drug baibu, radix Stemona and its allied drugs. I. Some textual studies on baibu]. PMID- 1418546 TI - [Immunological identification of tiger-bone]. AB - Anti-tiger sera were prepared by using tiger serum proteins to immunize the rabbits. Tiger-bone can be identified by the specific serological reaction between the anti-tiger sera and the tiger-bone proteins. PMID- 1418548 TI - [A preliminary study on growing tempo of Ophisourus harti Boulenger]. AB - Under experimental circumstances, the relationship between the growing tempo of Ophisourus harti and its age, fodder, outside temperature and humidity has surveyed. Suggestions have accordingly been made with regard to the rational utilization and protection of the resources. PMID- 1418547 TI - [Identification of morphology and inorganic elements of Eucommia ulmoides Oliv. produced in Sichuan by applying scanning electron microscope with energy dispersive X-ray analysis]. AB - A research on the identification of morphology and inorganic elements of Eucommia ulmoides produced in Sichuan has been made by applying scanning electron microscope; energy dispersive X-ray analysis. Qualitative and semi-quantitative analyses of the inorganic elements in the observed areas have been obtained. PMID- 1418549 TI - [Thin layer chromatographic studies on radix Ginseng, fructus Schisandrae and radix Salviae miltiorrhizae in yixinfumai granules]. AB - The main constituents of Radix Ginseng, Fructus Schisandrae and Radix Salviae Miltiorrhizae in Yixinfumai Granules were studied by TLC. It was found that ginsenoside got hydrolyzed while the drugs were being boiled together. The main constituents of Fructus Schisandrae were schizandrol A and B; and those of Radix Salviae Miltiorrhizae were tanshinone and protocatechuic aldehyde. PMID- 1418550 TI - [Constituents of tannins from Euphorbia prostrata Ait]. AB - Ten compounds have been isolated from Euphorbia prostrata and identified as gallic acid, corilagin, 1,2,3-tri-O-galloyl-D-glucose,geraniin,tellimagradin I, II, rugosin A, rugosin E, rugosin D and rugosin G on the basis of physicochemical and spectroscopic methods. PMID- 1418551 TI - [Chemical studies on immunologically active polysaccharides of Ganoderma lucidum(Leyss. ex Fr.) Karst]. AB - BN3B, the polysaccharide component of the fruit of Ganoderma lucidum, has been shown to have immune activity. From BN3B four homogeneous polysaccharides were separated and purified. Chemical studies on the main components BN3B1 and BN3B3 indicated that BM3B1 contained only glucose and should be a glucan containing beta-(1----6) and (1----3)glycoside bonds and that BN3B3 was an arabinogalactan containing beta-(1----6) and (1----3)glycoside bonds. PMID- 1418552 TI - [Chemical constituents of Isodon albopilosus (C.Y. Wu et H.W. Li) Hara]. AB - Five compounds have been isolated from the stems and leaves of Isodon albopilosus. On the basis of spectroscopic and chemical data, they were identified as macrocalyxin C, stearic acid, beta-sitosterol, ursolic acid and beta-sitosterol-beta-D-glucoside, respectively. PMID- 1418553 TI - [Chemical constituents of Vaccinium scopulorum W.W. Smith]. AB - Seven compounds were isolated from the radix of Vaccinium scopulorum. On the basis of spectral analysis, physico-chemical constants and derivative preparations, they were identified as beta-amyrin, 3-epi-ursolic acid, methyl maslinate, 3 beta-acetoxy-delta 7-cholest-7-ene, protocatechuic acid, ethyl n hexacosanoate and ethyl n-tetracosanoate respectively. PMID- 1418554 TI - [Relationship between serum level of zinc and copper and inhibitory effect of herba Asari oil on proliferation of granuloma induced by implantation of cotton pellets in rats]. AB - Intraperitoneal injection of the essential oil of Asarum himalaicum and A. heterotropoides var. mandshuricum may inhibit the proliferation of granuloma induced by implantation of cotton pellets in rats. This action might be related to the reduction of blood serum zinc. PMID- 1418555 TI - [Pharmacological study on spleen-stomach warming and analgesic actions of Aconitum carmichaeli Debx]. AB - This study presents an observation of the anti-inflammatory effect of Aconitum carmichaeli decoction on water-immersion stress induced gastric ulcer in mice and 0.6 mol/L HCl induced gastric ulcer in rats. The observation showed that the decoction was resistant to the castor oil induced and Cassia angustifolia leaf induced experimental diarrhea in mice, and also had marked analgesic action. It is thus suggested that Aconitum carmichaeli is useful clinically as a spleen stomach warming and analgesic agent in traditional Chinese medicine. PMID- 1418556 TI - [A preliminary exploration of the toxicity of certain Chinese herbal drugs containing alkaloids and the prevention of their poisoning]. PMID- 1418557 TI - [A histochemical study of saikosaponins]. AB - The root of Bupleurum chinese and B.scorzonerifolium was examined histochemically in order to clarify the distribution of saikosaponins in various tissues and parts of the root. By means of qualitative and quantitative analyses, saikosaponins, the bioactive principles in the root, were found to be abundant in the cortex outside the cambium and very little in the xylem of the root. It was also found that the thinner root hairs had the highest contents of saikosaponins, but decreased towards the thicker root head. PMID- 1418558 TI - [A new method of identifying Chinese crude drugs by comparing the characteristic content patterns of their chemical constituents]. AB - Using the characteristic patterns of contents of chemical constituents, Chinese crude drugs derived from closely relative species and their fakes can be clearly identified and the quality of these drugs can be roughly evaluated. In this paper, the identification of Qianghuo (Notopterygium spp.) was presented based on this new method. PMID- 1418559 TI - [Analysis of chemical constituent of essential oil in Lonicera japonnica Thunb. cultivated on the northern plain of Henan Province]. AB - The chemical constituents of the essential oil in the dry flower and fresh flower of Lonicera japonica were analyzed by the GC-MS-DS technique and the superimposition of authentic samples. 27 and 30 monoterpenoids and sesquiterpenoids were identified from the essential oil of the dry flower and fresh flower respectively. The major constituents have been found to be linalool, geraniol, aromadendrene and eugenol etc. PMID- 1418560 TI - [Determination of total alkaloid in seedling bulbs of Fritillaria thunbergii Miq]. AB - This paper reports the determination of total alkaloid in the seedling bulbs and cultivars of the traditional Chinese medicine Fritillaria thunbergii. The result shows that the content of total alkaloid reaches the standard value specified in Chinese Pharmacopeia, and thus is useful for further production of sexual propagation. PMID- 1418562 TI - [Optimization of preparing technology for qiju dihuang oral liquid by orthogonal method]. AB - L9(3)4 orthogonal experiment was performed to improve the clarity of Qiju Dihuang Oral Liquid. The result shows that the optimum pretreatment technology for the liquid includes alcohol concentration 75%, liquid pH 4.2 freezing temperature 3 degrees C and freezing time 48 hours. PMID- 1418561 TI - [Studies on sedative and anticonvulsion effects of differently processed rhizoma Typhon]. AB - Mice were employed to study sedative and anticonvulsion effects of Rhizoma Typhon processed by different methods. The results showed that processed and raw Rhizoma Typhon had marked sedative effect and delayed convulsion time, caused by cardiazole and strychnine. Processed and raw Rhizoma Typhon had similar action. With the new processing method, similar sedative and anticonvulsion effects were obtained compared with the old processing method. PMID- 1418563 TI - [A new method of enveloping volatile oils in Chinese medicinal herbs with beta cyclodextrin]. AB - A comparison has been made of the enveloping rate of volatile oil by three different methods with beta-cyclodextrin. The result indicates that the saturated water solution enveloping method is very close to the gas-liquid enveloping method, P greater than 0.05, but the liquid-liquid enveloping method is apparently higher than the saturated water solution enveloping method, P less than 0.01. PMID- 1418564 TI - [Flavonoids in the seed of Cuscuta chinensis Lam]. PMID- 1418565 TI - [Alkaloids of Annona reticulata L]. PMID- 1418567 TI - [Nourishing yin action of the prepared rhizoma Rehmanniae]. AB - The results of the experiment show that the prepared Rhizomae Rehmanniae can obviously improve the change of weight, quality of drinking water, urine and serum level of T3, T4 and AD of the hyperthyroid Yin deficient rats, and thus administers to the nourishing of Yin. The action of nourishing the kidney Yin is related with improving the serum level of AD in the body. PMID- 1418566 TI - [Constituents of the dry roots of Rehmannia glutinosa Libosch]. AB - From the extract of dry roots of Rehmannia glutimosa, fatty acids, palmitic acid, beta-sitosterol, daucosterol and sulfur (Ss) cyclic compound were isolated and identified. The latter four were isolated for the first time. PMID- 1418568 TI - [Effect of mieyanling oral liquid on the immune responses in normal and cyclophosphamide treated mice]. AB - It has been proved that Mieyanling in Vivo and in Vitro, can augment the lymphocyte transformation rate induced by PHA, Con-A or LPS in mice. The suppressed immune function caused by cyclophosphamide can also be significantly relieved by Mieyanling Oral Liquid. PMID- 1418569 TI - [Inhibition of fructus Corni on experimental inflammation]. AB - Fructus Corni (FC) decoction inhibits the increase of peritoneal capillary permeability by ip 0.7% acetic acid in mice, the proliferation of granuloma formed by implanting cotton pellets in rats, the swelling of mouse pinnea with xylene and the edema of hind paw induced by injection of fresh egg white 0.1 ml in rats. FC decreases the contents of ascorbic acid in adrenal, but has no marked effect on the contents of prostaglandin E in inflammatory tissue of rats. These results indicate that the inhibitory effect of FC on the inflammatory process may be related to pituitary-adrenal axis. PMID- 1418570 TI - [Primary observation on antidotal effect of the Chinese drug mutong against fuzi]. AB - Mutong can reduce Fuzi's toxicity markedly. This reducing effect is directly proportional to the dosage of Mutong within a certain range and the content of alkaloid in Fuzi drops clearly after Fuzi and Mutong are used in the same prescription. PMID- 1418571 TI - [Textual studies on fuxiong (Ligusticum chuanxiong Hort. cv. fuxiorg)]. PMID- 1418573 TI - [Identification of seven snake-drugs by iso-electric point]. AB - This paper deals with the identification of seven snake-drugs by means of iso electric point of protein. The experimental results show that different species of snake-drugs have different iso-electric points. The experimental data are accurate and easily reproducible (CV less than 0.5%). The difference of the averages of iso-electric points of the seven snake-drugs (P less than 0.01%) is extremely significant and thus provides a scientific criterion for the identification of peeled or powdered snake-drugs. PMID- 1418572 TI - [Quality of dihuang (Rehmannia spp.)]. AB - In this paper, the contents of catalpol, water-extract and alcohol-extract materials, ash, total reducing sugar and inorganic elements in Dihuang from different habitats have been measured. The result shows that Huai Dihuang, the genuine drug, excels all those from other habitats in quality. The quality of commercial dry Dihuang may be related closely to the production area, storage time, etc. PMID- 1418574 TI - [Cytological observation on culture of embryo in vitro of Tripterygium hypoglaucum (level.) Hutch]. AB - This paper for the first time reports the embryo culture in vitro of Tripterygium hypoglaucum. Callus, adventitious roots and adventitious protuberances were induced from the cultured embryos in vitro. Multi-buds at the excised embryo tip were also observed at the same time. Cytohistological examination showed (1) callus was histologically easy to be induced to form adventitious roots; (2) callus on the cotyledons was originated from the epidemical and subepidemical cells of the cotyledons, and the adventitious roots were originated from the disperse meristematic tissue or vascular tissue in the callus obtained from cultured excised embryos. PMID- 1418575 TI - [Types of flowering branch of Magnolia denudata Desr. under high yield conditions]. AB - The types of flowering branch of Magnolia denudata under high yield conditions were investigated. The action of axillary flowering branches on yield increase and the cultural techniques of promoting axillary flowering branch formation were evaluated. Under the same culturing conditions M. denudata var. dilutipurpurascens has hardly any axillary flowering branches. PMID- 1418576 TI - [Anti-inflammatory effect of differently processed rhizoma Typhon] off. AB - Rat was employed to study the anti-inflammatory effect of Rhizoma Typhon processed by different methods. The result showed that processed and raw Rhizoma Typhon had similar action. With the new processing method similar anti inflammatory effect was obtained compared with the old processing method. PMID- 1418577 TI - [Uniform design for the best conditions of processing heixi in shenrong heixi pills] off. AB - Uniform design has been applied to select the optimum technological conditions for processing Heixi in Shenrong Heixi Pills, using the contents of the main constituent of Heixi SNS as the optimum target. The best technological conditions have thus been found. PMID- 1418578 TI - [Preparation of sucking tablet of shengmei] off. AB - The Sucking Tablet of Shengmei is made from eight Chinese traditional drugs including Radix Adenophorae, Fructus Mume, etc. The effective rate of the tablet in treating chronic pharyngitis reaches up to 96 percent. The working mechanism related to the fact that the tablet is bacteria-resistant and helps to strengthen the body function. This paper presents the preparation process of the Sucking Tablet along with solutions for some problems encountered in the process and appropriate standards for quality control. PMID- 1418579 TI - [Effective chemical constituents of Artemisia argyi Levl. et Vant for inhibition of platelet aggregation]. AB - beta-Sitosterol and eupatilin were isolated and identified from Artemisia argyi. Both of them showed marked inhibition of platelet aggregation. PMID- 1418580 TI - [Chemical constituents of the roots of Ostericum grosseserratum (Maxim.) Kitag]. AB - This paper reports the isolation of eleven compounds from the roots of Ostericum grosseserratum, of which nine compounds were elucidated as myristic acid, palmitic acid, stearic acid, octacosanoic acid, succinic acid, beta-sitosterol, sitosterol-beta-D-glucoside, isoscopletin and sucrose. The results are helpful in the study of plant taxonomy. PMID- 1418581 TI - [Chemical constituents of the leaves of Acanthopanax trifoliatus (Linn) Merr]. AB - Nevadensin (A), kaur-16-en-19-oic acid (B), taraxerol (C) and taraxerol-acetate (D) were isolated from the leaves of Acanthopanax trifoliatus. A and B were isolated for the first time. Pharmacological experiments have shown that nevadensin possesses expectorant and antitussive actions. PMID- 1418583 TI - [Determination of cinnamaldehyde in cortex Cinnamomi by CS-930 TLC scanner]. AB - Cinnamaldehyde was extracted by chloroform from Cortex Cinnamomi and determined directly on a CS-930 TLC scanner. The method is simple and sensitive, and can serve as an index for checking the quality of Cortex Cinnamomi. PMID- 1418584 TI - [Effects of artificial cultured Panax notoginseng cell on cardiovascular system]. AB - Alcoholic extract from artificial cultured Panax notoginseng cell (SCC) ip has been found conducive to increasing the resistance of mice to anoxia. In vitro it helps to increase the outflow of coronary vessels, decrease the heart rate, inhibit the constriction of aortic strip stimulated by nor-epinephrine and relax spasmodic constriction of ileum smooth muscles markedly. SCC powder suspension on po administration can contract bleeding and coagulation time. The pharmacologic activities of SCC are similar to those of crude Panax notoginseng. PMID- 1418582 TI - [Isolation and identification of julibrotriterpennoidal lactone A from Albizia julibrissin Durazz]. AB - Julibrotriterpennoidal lactone A was isolated from the cortex of Albizia julibrissin. Its structure (the C28----C21 lactone of, 3 beta, 16 beta, 21 beta trihydroxy-delta 12-oleanen-28-oic acid) has been determined on the basis of spectral evidence (IR, 1HNMR, 13C NMR and MS). PMID- 1418585 TI - [Pharmacological study on Cordyceps sinensis (Berk.) Sacc. and ze-e Cordyceps]. AB - The Ze-e Cordyceps is similar to the Cordyceps sinensis in such pharmacological actions as calming, enduring hypoxia, dilating trachea, male sex hormone action, antiphlogistic and toxicity, etc. It is thus suggested that the Ze-e Cordyceps may be used place of the Cordyceps sinensis in clinical practice. PMID- 1418586 TI - [Studies of Rehmannia glutinosa Libosch. f. hueichingensis as a blood tonic]. AB - We have studied the function of dried and prepared Rehmannia glutinosa f. hueichingensis in treating hemorrhagic anemic mice and in fostering bone marrow hematopoietic cells CFU-S, CFU-E. The results show that Rehmannia glutinosa f. hueichingensis can promote the recovery of blood deficient animals, RBC. Hb expedite the multiplication and differentiation of CFU-S, CFU-E, and thus proves markedly helpful to the generation of blood. PMID- 1418587 TI - [Antioxidative effect of Chinese drugs]. AB - The antioxidative effect of more than 50 ethanol extracts of Chinese drugs were studied on the air oxidation of linoleic acid. Several ethanol extracts such as Glycyrrhiza uralensis, Magnolia officinalis and Zingiber officinale etc., were found having stronger antioxidative effect. PMID- 1418588 TI - [Pharmacological study of Zingiber officinale (Willd.) Rosc. and its clinical use]. PMID- 1418589 TI - [Advances in the pharmacological study of pollen Typhae]. PMID- 1418590 TI - A research agenda for pressure ulcer prevention. AB - The Agency for Health Care Policy and Research (AHCPR) Guideline Panel on Pressure Ulcers completed a comprehensive review of the literature related to the prediction and prevention of pressure ulcers in adults. On the basis of this review, the panel formulated a guideline for care. Additionally, the analysis of published research revealed gaps in knowledge, research issues, and methodological problems that need attention in future studies. The following were identified as focus areas for the future: research with pressure ulcers status as the outcome rather than other intermediate outcomes; studies of product and intervention efficacy; further delineation of pressure ulcer staging; refinement of risk assessment tools; and testing of risk-based multi-intervention trials. PMID- 1418591 TI - Defining characteristics of the nursing diagnosis "high risk for impaired skin integrity". AB - Medical records were retrospectively reviewed to examine factors which may predict skin breakdown in the hospitalized adult patient. One-hundred fourteen (114) subjects were selected for the study, 60 who developed skin breakdown and 54 who did not. Results suggested that the factors which predict skin breakdown in the hospitalized patient are: age greater than 65 years, decreased level of consciousness, low activity level, low-grade fever, presence of infection, incontinence, poor nutritional intake, and an altered metabolic state. PMID- 1418592 TI - Synthesis of research findings through meta-analysis. AB - Meta-analysis is an alternative, quantitative approach to the analysis and synthesis of multiple investigations of the same clinical question. The statistical approaches that have been developed since Glass coined the term meta analysis in 1976 are discussed. Clinicians will find meta-analysis helpful when there are conflicting research findings about perplexing clinical problems. PMID- 1418593 TI - Research basics: getting past gatekeepers. AB - In order to conduct research the investigator must first get beyond the "gatekeepers," the people who have the power or the influence to keep the research project from being investigated. Two factors that get researchers past gatekeepers are integrating some basic assumptions about all institutions and using selected practical strategies to gain entry. Basic assumptions include consideration of the institution as a dynamic social system encompassing territoriality issues, a resistance to change, and investment in maintaining good public relations. Practical strategies include communicating with the "right" people, "marketing" your proposal effectively, and creating a "win-win" situation. PMID- 1418595 TI - The need for simple and complex research. PMID- 1418594 TI - Pressure ulcer incidence and severity in a community hospital. AB - In a study of 1320 adult patients admitted to a community hospital, there was a pressure ulcer incidence rate of 8.4%, with 3.2% of pressure ulcers present on admission. Of the 190 ulcers found, 63% (n = 120) were hospital acquired and were less severe than those present on admission. There was an average of 1.6 ulcers per patient; 56.3% (n = 107) were Stage I ulcers and 36.3% (n = 69) were Stage II ulcers. The most frequent sites were coccyx-sacral area, heels, and elbows. Preventive measures used most frequently were turning, special mattresses, and special skin care. After a pressure ulcer developed, the most frequently used treatment measures were special bed or mattress, frequent turning, and special ointments and dressings. PMID- 1418596 TI - Review of AHCPR urinary incontinence in adults: a patient's guide. PMID- 1418597 TI - The role of functional imaging in neoplasms of the thyroid. AB - Iodine-123 and Iodine-131 have suitable physical properties that enable them to be used for functional imaging of the thyroid. Iodine-123 is used for routine testing for hyperthyroidism and thyroid nodules, whereas I-131, which has a longer half-life, is used for whole body imaging for detecting metastatic thyroid cancer in patients who have undergone thyroidectomy. The radionuclides of iodine are trapped and organified like nonradioactive iodine. In contrast, technetium as pertechnetate is trapped by the thyroid and can be used for imaging immediately after intravenous injection. There can be differences in scintiscans made in the same patient using radioiodine vs. technetium. Thallium is a useful adjuvant imaging agent for thyroid cancer. It should be stressed that correlation with the clinical findings and biochemical thyroid function tests are very important when evaluating thyroid scintiscans. PMID- 1418598 TI - Proteoglycans in cell regulation. AB - Proteoglycans are a diverse group of proteins carrying one or more glycosaminoglycan side chains linked to the protein as O-glycosides. Our appreciation of these structures has matured from a curiosity about unusual structural glycoproteins, to confer upon them a central role in cell biology. The major classes of glycosaminoglycans are heparan sulfate and heparin, chondroitin and dermatan sulfates, keratan sulfate and hyaluronic acid. The latter is unique in that it does not contain sulfate residues, and appears to be synthesized, at least sometimes, free of a carrier protein. There is now a wealth of information on the ability of these structures to influence the growth and development of cells and tissues. Many direct and specific effects of proteoglycans will undoubtedly be found, and there are likely to be indirect effects of the glycosaminoglycans relating to their polyelectrolyte nature. Convincing arguments that biological activity resides in certain proteoglycan core proteins are also appearing. The following discussion concerns the role of proteoglycans in the regulation and action of autocrine and polypeptide growth factors, direct mitogenic and antimitogenic actions of glycosaminoglycans, the role of these structures in regulating gene expression, and the biological activities of proteoglycan core proteins. The probable role of proteoglycans in normal glomerular cell function, and in progressive renal disease, will be presented as a harbinger of the significant role we can expect them to play in diagnosis and therapy in the near future. PMID- 1418599 TI - Biochemistry of alcoholic liver disease. AB - The biochemistry of alcohol liver disease as it relates to clinical medicine and experimental alcohol liver disease is presented. Clinical features are emphasized in the diagnosis of alcohol liver disease, particularly as it relates to staging the disease and predictors of prognosis. Currently, it is true that the biochemical diagnosis of alcohol liver disease is at best very limited in terms of the sensitivity tests and specificity of the test. It is particularly difficult to detect alcohol liver disease biochemically in the early stages when steatohepatitis is not severe. Consequently, 50% of the patients have already developed cirrhosis at the time they are diagnosed clinically. In this review indicators of malnutrition are emphasized because they have the strongest implications regarding survival during the acute hospitalization stage of the disease. They are also the best indicators of response to therapy during the recovery phase. With respect to experimental work on the pathogenesis of alcohol liver disease, it appears that necrosis is due to the inability to increase blood flow to compensate for increased oxygen utilization. The hypothesis that mitochondrial damage is the cause of liver cell damage is regarded as less important in the pathogenesis of necrosis. The shift in the redox state during alcohol metabolism accounts for the fatty change noted in the central lobular area of the liver in animals fed alcohol. Apparently, there is strong experimental evidence that highly reactive intermediates are important in the pathogenesis of liver damage due to the induction of the isozyme cytochrome P450 IIE1 by alcohol ingestion. This mechanism is enhanced by a diet high in polyunsaturated fatty acids. PMID- 1418600 TI - Application of immunochemical assays to food analysis. AB - Immunochemical assays are powerful bioanalytical techniques with application to several areas in food science, including food analysis, microbiology, nutrition, food safety, food quality, and process control. In principle, immunochemical techniques can be applied to the analysis of any compound, with only one specific antibody needed that can be obtained either from laboratory animals or, when available, from commercial sources. A well-designed immunochemical assay can detect targeted compounds at levels as low as 10(-12) M. Immunochemical techniques require little or no sample pretreatment, making these analytical procedures relatively rapid. The initial cost of developing an immunoanalytical assay may be high, but when the procedure is well established, the cost per test is often a fraction of that for other analytical methods. For these reasons, immunoanalytical assays provide an attractive alternative for the food analyst who requires either inexpensive qualitative screening tests or reliable quantitative methods with a high degree of sensitivity. This review concentrates on the use of enzyme immunoassay to address analytical problems in food chemistry and the analysis of various food components. PMID- 1418601 TI - Characteristics of antisweet substances, sweet proteins, and sweetness-inducing proteins. AB - Recent studies on structures and functions of sweetness-inhibiting substances (gymnemic acid, ziziphin, and gurmarin); sweet proteins (monellin, thaumatin and mabinlin); and taste-modifying proteins (miraculin and curculin) were reviewed. Several gymnemic acid homologues and gurmarin were purified from the leaves of Gymnema sylvestre and their structures were determined. Ziziphin was also purified from leaves of Ziziphus jujuba. Gymnemic acid and ziziphin are glycoside of triterpenes that suppress sweetness in human, while gurmarin is a peptide having antisweet activity in rat. Mabinlin is a heat-stable sweet protein. The whole amino acid sequence and the position of disulfide bridges of mabinlin were determined. Miraculin has the unusual property of modifying a sour taste into a sweet taste. Curculin elicits a sweet taste. In addition, water and sour substance elicit a sweet taste after curculin. Their amino acid sequences and subunit structures were determined. These proteins are expected to be used as low calorie sweeteners. PMID- 1418602 TI - Inhibition of enzymatic browning in foods and beverages. AB - Enzymatic browning is a major factor contributing to quality loss in foods and beverages. Sulfiting agents are used commonly to control browning; however, several negative attributes associated with sulfites have created the need for functional alternatives. Recent advances in the development of nonsulfite inhibitors of enzymatic browning are reviewed. The review focuses on compositions that are of practical relevance to food use. PMID- 1418603 TI - Macromolecule replacers in food products. AB - Traditional macromolecules and other recently synthesized materials have been accepted by consumers for use as low-calorie replacements for fats and sugars in food products. These include carbohydrates such as polydextrose, maltodextrins, modified starches, gums, and fibers. Protein and lipid-based replacements, including fat analogs and emulsifiers, are also available and some have been approved for use in food products. This article presents the properties of each of the macromolecule replacers, some uses that have been reported in food products, and speculative thoughts regarding functionality. Because control of water in the food product, added solids, and the mouthfeel characteristics associated with microparticles are three of the critical functions that must be provided by replacers, effectiveness of usage from a sensory perspective is also considered. PMID- 1418604 TI - Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. AB - Studies conducted in many laboratories over the past several years have resulted in the identification and initial characterization of a large superfamily of structurally and functionally related inflammatory cytokines. This superfamily currently includes 14 distinct members: platelet factor 4, beta-thromboglobulin, neutrophil activating peptide-1/interleukin-8, gro, IP-10, mig, ENA-78, macrophage inflammatory proteins-1 alpha and -1 beta, monocyte chemoattractant protein-1/JE, RANTES, HC-14, C-10, and I-309. Although numerous biological activities have been assigned to these molecules, a common theme is their ability to stimulate the chemotactic migration of distinct sets of cells, including neutrophils, monocytes, lymphocytes, and fibroblasts. Accumulating evidence indicates that these molecules play important roles in mediating cell recruitment and activation necessary for inflammation and the repair of tissue damage. PMID- 1418605 TI - Pitfalls of CT appearance of adrenal glands in lung cancer patients. PMID- 1418606 TI - Computerized tomography of colonic diverticulitis. AB - In this review article, the value of computerized tomography (CT) vs. contrast enema (CE) in patients with acute diverticulitis is discussed. Acute diverticulitis is a frequent differential diagnosis in abdominal disease. Approximately 15 to 30% of all patients with diverticulosis develop diverticulitis, whereby approximately 21% of these must undergo surgery. The clinical as well as the radiographical differential diagnosis between diverticulosis and diverticulitis often poses a great problem. While the contrast enema demonstrates the changes of the intestinal lumen, the true extent of the inflammatory process cannot be estimated. Numerous studies have shown that CT is preferable in demonstrating the extent of pericolic inflammation, which is often underestimated with the contrast enema. Within the range of computer tomographical symptoms, infiltration and colonic wall thickening show a high sensitivity. These CT symptoms are not pathognomonic. The differential diagnosis of the findings with CT is discussed. PMID- 1418607 TI - US and CT evaluation of diffusely enlarged adrenal gland. AB - Normal adrenal gland contains an anteromodial ridge and two asymmetric wings. This results in the characteristic features of cross-sectional images in different levels of a section. When adrenal gland is diffusely enlarged, it initially becomes thickened. As it grows larger, it may stimulate a focal mass lesion or it may appear irregular in shape. However, the basic forms in different section planes are still somewhat maintained. In bilateral adrenal hyperplasia, the medulla may be seen as a highly echogenic linear structure on US and a high density linear structure on CT. The other causes of diffuse adrenal enlargement are hemorrhage, infectious disease, infiltrating neoplastic disease, and congenital metabolic deficiency disease. PMID- 1418608 TI - CT evaluation of the abdominal wall. AB - Computed tomography (CT) is a useful method for evaluating the abdominal wall. Pathology includes hernia, hematoma, infection and inflammation, tumor, and post traumatic, post-operative, and miscellaneous conditions. The CT findings of these various abnormalities are presented. PMID- 1418609 TI - Programming of lymphocyte responses to activation: extrinsic factors, provided microenvironmentally, confer flexibility and compartmentalization to T-cell function. PMID- 1418610 TI - Induction, regulation and function of T-cell subsets in leishmaniasis. PMID- 1418611 TI - Delayed-type hypersensitivity recruitment of T cell subsets via antigen-specific non-IgE factors or IgE antibodies: relevance to asthma, autoimmunity and immune responses to tumors and parasites. PMID- 1418612 TI - T helper cell immune dysfunction in asymptomatic, HIV-1-seropositive individuals: the role of TH1-TH2 cross-regulation. PMID- 1418613 TI - Staphylococcal enterotoxins, toxic shock syndrome toxin and streptococcal pyrogenic exotoxins: a comparative study of their molecular biology. PMID- 1418614 TI - Effects of staphylococcal toxins on T-cell activity in vivo. PMID- 1418615 TI - Mycoplasma arthritidis-derived superantigen. PMID- 1418616 TI - Cellular and molecular mechanisms of immune activation by microbial superantigens: studies using toxic shock syndrome toxin-1. PMID- 1418618 TI - Germ-line-encoded recognition of certain short peptide antigens? PMID- 1418617 TI - T-cell-dependent shock induced by a bacterial superantigen. PMID- 1418619 TI - T-lymphocyte stimulation by microbial superantigens. PMID- 1418620 TI - Mls antigens: immunity and tolerance. PMID- 1418621 TI - Platelet-derived growth factor isoforms AA, AB, and BB differentially activate poly r(I):r(C)-induced genes in human fibroblast FS4 cells. AB - Polyribocytidylic-polyriboinosinic acid [poly r(I):r(C)]-inducible genes were isolated by a differential screening procedure from a human fibroblast cell (FS 4) cDNA bank. Among yet unidentified genes (gene 274), one codes for a protein with multiple finger motifs and has previously been detected in endothelial cells after tumor necrosis factor-alpha (TNF-alpha) treatment (A20; Opipari et al., 1990), the second one codes for a variant of the I kappa B family (Haskill et al., 1991), and a third one for the Ca2+ ATPase (isoform 1). Platelet-derived growth factor (PDGF) isoforms (AA, AB, and BB) stimulated the expression of these immediate-early genes. But the extent of the respective induction correlated neither with the number of the two receptors alpha or beta nor with the level of PDGF-stimulated receptor autophosphorylation on tyrosine. Although alpha receptors were less abundant than beta-receptors (12,500 binding sites were estimated for PDGF-AA, KD 0.03 nM; 20,000 for PDGF-AB, KD 0.03 nM; 35,000 for PDGF-BB KD 0.16 nM) and tyrosine phosphorylation induced by PDGF-AA was significantly less than that evoked by PDGF-BB, some of the investigated genes were more strongly induced by PDGF-AA. We discuss how the differences in the biological potency of the PDGF isoforms may reside in different functions of the two receptors by activation of alternative signaling pathways. PMID- 1418623 TI - Molecular cloning and functional characterization of chicken cathepsin D, a key enzyme for yolk formation. AB - Upon receptor-mediated endocytosis of very-low-density lipoprotein (VLDL) and vitellogenin into growing chicken oocytes, the protein moieties of these lipoproteins are proteolytically cleaved. Unlike the complete lysosomal degradation in somatic cells, enzymatic ligand breakdown in oocytes generates a characteristic set of polypeptides, which enter yolk storage compartments for subsequent utilization by the embryo. Here, we demonstrate directly that the catalyst for the intraoocytic processing of both apolipoprotein B and vitellogenin is cathepsin D. The enzyme was purified from oocytic yolk, preovulatory follicle homogenates, and liver by affinity chromatography. When plasma VLDL and vitellogenin were incubated with the purified enzyme, fragments indistinguishable from those found in yolk were generated from both precursors under identical, mildly acidic conditions. Amino-terminal sequencing of the pure enzyme demonstrated 88% identity with mammalian cathepsin Ds over 34 residues. On the basis of this information, a full-length clone specifying chicken preprocathepsin D was isolated from a chicken follicle cDNA library by screening with a human cathepsin D probe. Whereas previous studies have demonstrated that the receptors for lipoproteins in somatic cells and oocytes, respectively, of the chicken are the products of different genes, Southern and Northern blot hybridization experiments showed that the enzymes expressed in oocytes and liver are the product of a single gene, giving rise to a 3.3-kb transcript. The primary structure of the 335-residue mature protein suggests a high degree of conservation of known crucial features of aspartyl proteases; however, the absence of the so-called processing region and of an aromatic residue in a region thought to partake in catalysis raise questions with possible evolutionary implications. PMID- 1418622 TI - Complementary DNA cloning and expression of Pit-1/GHF-1 from the domestic turkey. AB - The transition from egg laying to incubation activity in birds is associated with a dramatic rise in serum prolactin levels. To further our understanding of the regulation of prolactin gene expression in birds, a cDNA clone encoding turkey Pit-1/GHF-1 was isolated. The turkey cDNA, designated tPit-1/GHF-1, was 1,123 nucleotides in length and encoded a protein of 327 amino acids, including a conserved 80-amino-acid POU-specific domain and a 60-amino-acid POU homeodomain. tPit-1/GHF-1 POU-specific domain and POU-homeodomain showed 94-95% amino acid identity with the corresponding rat Pit-1/GHF-1 domains. At its amino terminus, tPit-1/GHF-1 contained a 26-amino-acid insertion comparable to that found in the rat variant isoform, Pit-1 beta. Two other insertions of 38 and 7 amino acids were present and were not found in the mammalian protein. Levels of tPit-1/GHF-1 mRNA in pituitary tissue were examined at different phases of the turkey reproductive cycle by Northern blotting. tPit-1/GHF-1 mRNA was expressed as a 3.5 kb transcript, whose abundance remained relatively constant throughout the reproductive cycle. Thus, the dramatic rise in prolactin mRNA, observed during hyperprolactinemia in incubating turkey hens, was not associated with a concomitant increase in tPit-1/GHF-1 gene expression. PMID- 1418624 TI - Structure of the tilapia (Oreochromis mossambicus) prolactin I gene. AB - The tilapia (Oreochromis mossambicus) prolactin-I (PRL-I) gene has been cloned and sequenced. Its transcript (3,677 bases long) begins with a guanine and is organized in five exons and four introns like the other known prolactin genes. Analysis of the 1,555-bp 5'-flanking region suggests that pituitary-specific expression of the gene could be regulated through a trans-factor related to the mammalian pituitary-specific factor Pit-1. Two potential binding sites for such a factor were found in the first intron, suggesting a possible regulatory role for this region. Moreover, two potential Z-DNA regions are located at positions -837 to -812 and -246 to -179 from the transcription start site. These two regions could play an important role in the regulation of PRL gene expression. PMID- 1418625 TI - Cloning, sequencing, and disruption of the gene encoding sterol C-14 reductase in Saccharomyces cerevisiae. AB - A sterol C-14 reductase (erg24-1) mutant of Saccharomyces cerevisiae was selected in a fen1, fen2, suppressor background on the basis of nystatin resistance and ignosterol (ergosta-8,14-dienol) production. The erg24-1 allele segregated genetically as a single, recessive gene. The wild-type ERG24 gene was cloned by complementation onto a 12-kb fragment from a yeast genomic library, and subsequently subcloned onto a 2.4-kb fragment. This was sequenced and found to contain an open reading frame of 1,314 bp, predicting a polypeptide of 438 amino acids (M(r) 50,612). A 1,088-bp internal region of the ERG24 gene was excised, replaced with a LEU2 gene, and integrated into the chromosome of the parental strain, FP13D (fen1, fen2) by gene replacement. The ERG24 null mutant produced ergosta-8,14-dienol as the major sterol, indicating that the delta 8-7 isomerase, delta 5-desaturase and the delta 22-desaturase were inactive on sterols with the C14 = 15 double bond. PMID- 1418626 TI - Sequence of the gene encoding the mitochondrial capsule selenoprotein of mouse sperm: identification of three in-phase TGA selenocysteine codons. AB - The mitochondrial selenoprotein is a major structural protein of the keratinous mitochondrial capsule in mammalian sperm, a structure that functions in shaping mitochondria into the helical sheath surrounding the flagellum. A cDNA clone (Kleene et al., 1990) was isolated previously encoding a protein whose predicted size and amino acid content of > 20% cysteine and proline closely resembled a selenoprotein in the bull mitochondrial capsule. The sequences of additional cDNAs and genomic DNA reported here reveal that the mouse mitochondrial capsule selenoprotein reading frame begins 54 codons further upstream than previously reported. Significantly, these 54 codons contain three in-phase UGA codons, which normally signify stop but encode selenocysteine in bacterial and mammalian selenoproteins. The coding region of the mitochondrial capsule selenoprotein gene is interrupted by a single intron. S1 mapping and primer extension demonstrate that the vast majority of MCS mRNAs are spliced using consensus 5' and 3' slice junctions in mammalian cells. However, two cDNAs have been identified that apparently represent rare mRNA variants produced by use of cryptic splice sites. PMID- 1418627 TI - Recombinant human acid alpha-glucosidase generated in bacteria: antigenic, but enzymatically inactive. AB - Genetic deficiency of acid alpha-glucosidase (GAA) results in glycogen storage disease type II. To investigate whether we could generate a functional recombinant human GAA protein for future enzyme replacement therapy, we subcloned the GAA cDNA into the bacterial expression plasmid pMaI and analyzed the recombinant protein produced. This nonglycosylated recombinant human GAA was found to be antigenic by reacting with polyclonal rabbit antibody to human placental GAA using ELISA and Western techniques. However, the protein was not enzymatically active, suggesting that glycosylation may play a role in enzymatic function. PMID- 1418629 TI - [Relative mortality trends for diabetes mellitus in the Brazilian state capitals, 1950-1985]. AB - The article describes the trend of relative mortality from diabetes mellitus in the capitals of the Brazilian states and territories from 1950 to 1975 (by place of occurrence) and from 1977 to 1985 (deaths of inhabitants) on the basis of data obtained from the statistical yearbooks of Brazil and the Ministry of Health's mortality statistics. It also presents the importance of relative mortality from diabetes mellitus in each capital by sex and age group, starting with age 20. In the earlier time period this mortality was found to be on the rise at a rate of increase varying between 1.7 and 11.1 and with an average rate of increase of 3.4 for all capitals. In the latter period the rate ranged between 0.5 and 2.7, with an average rate of 1.5 for all capitals. The death rates were proportionally highest between the ages of 50 and 69, and were higher among women. The study also comments on underestimation of this mortality when the primary cause of death alone is considered. PMID- 1418630 TI - [Genetic evidence of a species complex in Anopheles pseudopunctipennis pseudopunctipennis]. AB - In light of inconsistencies in the pattern of malaria transmission within geographical areas inhabited by Anopheles pseudopunctipennis pseudopunctipennis, a study was carried out to investigate the possibility that this vector constitutes a species complex. Hybrid crossing studies, electrophoretic analysis of enzyme loci, and DNA restriction analysis were conducted on mosquitoes captured at nine sites in Mexico, Bolivia, and Peru. The sterility of generations resulting from cross-mating of Mexican female mosquitoes and South American male mosquitoes; the results of electrophoretic analysis, which showed differences at two loci; and a genetic distance value of 0.13 confirmed the existence of a species complex, probably produced by allopatric speciation. It is concluded that the geographic distribution of this newly discovered species complex should be defined, in view of its potential effect on malaria control. PMID- 1418631 TI - [Competence levels]. PMID- 1418628 TI - Specific DNA amplification utilizing the polymerase chain reaction and random oligonucleotide primers: application to the analysis of antigen receptor variable regions. AB - The polymerase chain reaction (PCR) allows rapid amplification of DNA of known sequence. In many situations, part of a genetic sequence is known, but adjacent sequences of interest are unknown. This is common in investigations of antigen receptor genes from B and T lymphocytes, which are composed of a constant region of known sequence and a variable region, for which the sequence may not be known. Herein is described a method to amplify DNA when sequence information is available for only one primer. This procedure utilizes a primer of known sequence in conjunction with a mixture of short random primers. Application of this method to the amplification of T-cell antigen receptor cDNA is described. PMID- 1418632 TI - [Many plans have been realized in the course of years. 10 year VGV (Society for the History of Nursing)]. PMID- 1418633 TI - [Environment and health care (1). Environmental problems of today]. PMID- 1418634 TI - [The GIGV Report on aggression (Medical Inspection for Mental Public Health)]. PMID- 1418635 TI - [Safety and aggression in psychiatry]. PMID- 1418636 TI - [Beatrixoord Hospital in Haren--coughing politely]. PMID- 1418637 TI - [The PGGM (Foundation Pension Fund for Health, Mental and Social Affairs), or providing for later. 'We have 100 guilders in personal properties']. PMID- 1418638 TI - [Does the nurse get a flu shot?]. PMID- 1418639 TI - [Professional Profile Nursing. Who will do something with it?]. PMID- 1418640 TI - Degradation of tauromustine (TCNU) in aqueous solutions. AB - The stability of tauromustine in buffered aqueous solutions was investigated over the pH range 0.9-7.5. The pH rate profile at zero buffer concentration has a specific acid catalytic region at pH below 2, a plateau of pH-independent degradation between pH 2 and 4, and shows a sharp increase in the degradation rate at pH above 4. The activation parameters, the solvent isotope effect and the effect of the dielectric constant on the degradation rate were determined, and possible degradation mechanisms were discussed. The effects of six cyclodextrin (CD) derivatives on the stability of tauromustine in aqueous buffer solutions were investigated. All the CDs tested had some stabilizing effect on the drug at pH 1.98 and 4.06 but they had little or no effect at pH 6.38. Hydroxypropyl-alpha cyclodextrin (HP alpha CD) had the largest stabilizing effect. Tauromustine degraded about 25 to 50% slower in aqueous buffer solutions containing 2% HP alpha CD compared to buffer solutions containing no CD. PMID- 1418641 TI - Chemical stability of insulin. 3. Influence of excipients, formulation, and pH. AB - The influence of auxiliary substances and pH on the chemical transformations of insulin in pharmaceutical formulation, including various hydrolytic and intermolecular cross-linking reactions, was studied. Bacteriostatic agents had a profound stabilizing effect--phenol > m-cresol > methylparaben--on deamidation as well as on insulin intermolecular cross-linking reactions. Of the isotonicity substances, NaCl generally had a stabilizing effect whereas glycerol and glucose led to increased chemical deterioration. Phenol and sodium chloride exerted their stabilizing effect through independent mechanisms. Zinc ions, in concentrations that promote association of insulin into hexamers, increase the stability, whereas higher zinc content had no further influence. Protamine gave rise to additional formation of covalent protamine-insulin products which increased with increasing protamine concentration. The impact of excipients on the chemical processes seems to be dictated mainly via an influence on the three-dimensional insulin structure. The effect of the physical state of the insulin on the chemical stability was also complex, suggesting an intricate dependence of intermolecular proximity of involved functional groups. At pH values below five and above eight, insulin degrades relatively fast. At acid pH, deamidation at residue A21 and covalent insulin dimerization dominates, whereas disulfide reactions leading to covalent polymerization and formation of A- and B-chains prevailed in alkaline medium. Structure-reactivity relationship is proposed to be a main determinant for the chemical transformation of insulin. PMID- 1418642 TI - In vitro diffusion cell design and validation. II. Temperature, agitation and membrane effects on betamethasone 17-valerate permeation. AB - An in vitro permeation cell has been designed and validated for use in monitoring the transmembrane permeation of betamethasone 17-valerate. The design utilizes common laboratory equipment and incorporates as many beneficial features as possible from other designs. The importance of fully validating the hydrodynamic performance of the cell prior to experimentation is stressed. The cell was validated by monitoring the diffusion of betamethasone 17-valerate in isopropyl myristate solution into purified isopropyl myristate receptor phase at different temperatures, different agitation rates and through different synthetic and biological membranes. The results of the hydrodynamic validation agree with data from other researchers and show that the permeation cell is adequately sensitive to these experimental parameters. The results of the membrane evaluation allow appropriate selection of the barrier material for representative transdermal experiments to be conducted. While human and porcine stratum corneum/epidermis are similar in diffusive properties, hairless mouse skin appears to be the most convenient animal membrane for these studies. Although silicone and cellulose membranes appear to be useful in this application, porous filter membranes and egg-shell membranes are insufficiently discriminatory to betamethasone 17 valerate diffusion to provide useful in vitro permeation data. PMID- 1418643 TI - Human skin permeability studies of desmopressin and some prodrug derivatives. PMID- 1418644 TI - Hodgkin's disease. PMID- 1418645 TI - [Teratology and epidemiology in the study of environmental teratogens]. AB - The processes of cellular migration, cellular differentiation and cellular multiplication are studied, since these are the basic developmental processes upon which teratogenic agents act resulting in congenital malformations. We also carefully analyze the interactions between teratogen-embryo in order to establish adequate parameters for analysis of environmental teratogens, as well as experimental teratogenesis and epidemiology. Information on the pathogenesis of congenital malformations obtained from experimental teratology in an adequate biological model, can be extrapolated to the human. The etiology of congenital malformations resulting from environmental teratogens can only be elucidated through epidemiology, since there is species specificity. Such a study must fulfill the following prerequisites: diagnosis of the congenital malformation, ruling out genetic factors in the family tree and determination of the exact time of exposure to the possible teratogen during the pregnancy. PMID- 1418646 TI - [Coverage of 4 health programs for pre-school children in marginal urban areas in Mexico City]. AB - The aim this paper was to evaluate the coverage provided by four preschool child health programs (vaccinations, oral hydration therapy, healthy child care and sick child care). To make coverage operational, we designed indicators to compare the utilization of each program with the condition or health problems considered as needed. These results are part of a broad evaluative research called "Coverage and Quality of Primary Health Care" (CQPHC) carried out by the National Institute of Public Health (NIPH) in the State of Mexico in 1988. The population under study was a random sample of the total of preschool children detected in the household survey. We only analyzed data including children from 1-4 years to ensure that all studied children had completed the basic vaccination schemes. For the vaccination program, we observed a coverage of 47.7%, twice as much as that of the oral hydration program that only reached was 21.9%, whereas that of the sick child care program was 63.8%, the former being 2.0 times less than the latter. We can conclude that the different coverage found for each program is basically due to the lack socialization of the concept of need and to the extent of participation of the concept to make these services available to the population. PMID- 1418647 TI - [Epidemic outbreak of viral meningitis caused by type 30 ECHO virus]. AB - The clinical records of 15 children admitted to Hospital Infantile de Mexico Federico Gomez with diagnosis of viral meningitis were reviewed. They were part of 19 patients admitted with this diagnosis during a 5 week period (March 22 to April 30, 1992) and represent a significant increase of aseptic meningitis compared with the same periods of previous years at Hospital Infantile de Mexico and in Mexico City where there is an ongoing epidemic outbreak of this entity. All the patients studied had spinal fluid findings consistent with viral meningitis and in 4 of them on ECHO virus type 30 was isolated at the Enterovirus Section of the CDC, Atlanta Georgia USA. PMID- 1418648 TI - [Percentile curves of growth in macrosomic newborn infants in their first 2 years of life]. AB - Between February 1989 to August 1991, 184 macrosomic newborns were somatometrically evaluated during their first 12 hours of age (weight above 4000 g and height above 52 cm). They have a longitudinal follow-up at the Growth Clinic, of the National Institute of Perinatology, in Mexico City, during their first two years of age. All the infants without exception were feeding only with breast milk or protein modificative milk. The ablactation were since the four months of age with the same nutritional pattern. The macrosomic newborn maintain a higher velocity of growth, as a logarithmic kind, at the first two years of age with early cephalotoracic inversion, with maintenance of a big corporal pattern. We conclude that is useful to count with specific growth curves for macrosomic infants since their speed and rhythm of growth are different than for the adequate birth and low birth weight infants and even the macrosomic children of diabetic mother. PMID- 1418649 TI - [Effects of clonidine++ administration in children with familial short stature and retarded body growth]. AB - The effect of chronic clonidine administration on the height velocity of two groups of children with short stature either familial (FSS) or with constitutional growth delay (CGD) is presented. The patients whose age ranged between 5 to 12 years had a height below the third percentile; otherwise they were healthy. Both groups received 100 micrograms/m2 of clonidine orally during 12 months. In the group with FSS there was an increase in height velocity from 3.6 +/- 0.6 cm/years pretreatment values to 5.1 +/- 0.9 cm/years. The group with CGD showed an increase from 3.6 +/- 0.7 cm/years to 6.5 +/- 3.4. No secondary reactions were observed. The possible impact of this treatment on final height is discussed. PMID- 1418650 TI - [Rapid detection of neurologic morbidity in full term newborn infants]. AB - The purpose of this study is to evaluate the efficacy of the simplified method to detect neurological morbidity in newborn and to estimate the predictive parameter, i.e. sensitivity, specificity and predictive value. The sample consisted of 100 newborn infants from the Maternity Clinic of Hospital Regional Docente Trujillo-Peru, during the period from March to May 1990. All infants were born full-term, of normal delivery and Apgar score of greater than or equal to 7 at one minute, and no congenital malformation were present. Each one of the newborn was evaluated with a complete neurologic examination and the simplified method. Previously, the effects of population variables had been evaluated: the mean birth weight was 3277 g. (S.D. 435). Seventy one percent of the infants were between 38.5 and 39.5 weeks of gestational age. Eighty five percent of cases, showed on Apgar score from 8 to 10. The results allowed to determine that the sensitivity of the rapid neurological assessment was 0.70 specificity 0.75 and predictive value 0.75 (P less than 0.01). These findings suggest the usefulness and convenience of the method to detect neurological morbidity in full-term newborn infants. PMID- 1418651 TI - [Whorls and spirals in scalp hair. Possible clinical implications]. AB - The worl and cow-like shape scalp hair patterns. They are patterns considered normal and others aberrant. Because they are associated with disorders of early brain and craniofacial development, 300 newborn infants were studied. Only 6 had congenital malformation without anomaly scalp hair patterns associated. In the rest of newborn infants the location and direction of the whorls and cow-like were the same see in the children studied previously. Are necessary big series for affirm if really exist aberrant patterns. PMID- 1418652 TI - [Septic thrombosis of cavernous sinuses. Report of 2 cases]. AB - We report two male adolescents who developed septic thrombosis of the cavernous sinuses after manipulation of a furuncle on the nasal dorsum. We noted in both patients, besides the clinical findings of a generalized infectious process, palpebral edema, proptosis, ptosis, altered pupillary reactivity and bilateral III, IV and VI nerve palsies, as well as dysfunction of the ophthalmic branch of the fifth cranial nerve. One of the patients also had bacterial meningitis. Their cerebral angiograms demonstrated narrowing of the intracavernous portion of both internal carotid arteries. They improved with the antimicrobial treatment, but were left with ptosis and ocular palsies as sequelae. The adequate management of facial furuncle to prevent such a serious complication is emphasized. PMID- 1418653 TI - [Bronchogenic cyst. Presentation of 2 cases and review of the literature]. AB - The bronchogenic cyst is a congenital malformation of the tracheobronchial tree. It is not frequently seen in the pediatric population and had its origin around the sixth week of gestation when the bronchial development stops. Two cases of intraparenchymal bronchogenic cyst with lobar involvement of the right lung is presented. It was suspected after carefully examining and X-ray of the thorax and it was confirmed with ultrasonography and CT scan. There were no other associated malformations. The clinical and radiological diagnosis is extremely important for achieving the correct surgical procedure. This 2 patients was treated by thoracotomy and pulmonary lobectomy. PMID- 1418654 TI - [Pelger-Huet anomaly and hereditary elliptocytosis in 2 siblings]. AB - The Pelger-Huet anomaly (PHA) and the hereditary elliptocytosis (HE) are alterations affecting leukocytes and erythrocytes, respectively. Most of the affected individuals do not present clinic manifestations and are casually detected in the laboratory. The PHA and HE were described related to other hereditary and congenital conditions, but rarely have been found in the same individual. In this paper are reported discovery of the PHA and HE combined both in sister and brother, with global delay of development and peculiar physical characteristics. Blood smears of both showed an increase of bilobed neutrophils and elliptic erythrocytes. The family study showed two more members of the mother's branch affected with HE. The PHA could not be found in the parents, nor the other members of both branches. The early deaths or in uterus of three sibs of the propositus are appointed. The absence of the PHA in both parents of the affected individuals,--without discarding the illitimacy possibility--, can be explained by an incomplete genetic penetrance. The early or in uterus deaths of three sibs of the propositus seems possible that in some cases the combination of PHA and HE could be lethal. Possibly in Mexico this may be the first report of the presentation of the PHA and HE simultaneously in the same individual. PMID- 1418655 TI - [Understanding and diagnosis of complex congenital cardiopathies. II]. AB - Once the rules for understanding of complex congenital heart disease were reviewed in part I, the purpose in this second part is show how the clinical diagnosis is made. The first requirement is to separate patients into two groups: neonates and infants. A critical route based on five clue data: patient's age, presence or absence of cyanosis, presence or absence of myocardial failure, pulmonary blood flow estimated on x chest film, and presence of either right or left ventricular hypertrophy or both in ECG, is matched. This approach is helpful to reduce possibilities to diagnosis in congenital heart disease. PMID- 1418656 TI - Combined effects of ethanol and protein deficiency on hepatic iron, zinc, manganese, and copper contents. AB - The present study has been performed in order to establish the relative and combined roles of ethanol and malnutrition on liver Fe, Zn, Cu, and Mn alterations in alcoholic male adult Wistar rats, and also the relationships between these alterations and histomorphometrically determined hepatocyte and nuclear areas, perivenular fibrotic rim area, and total amount of fat present in the liver. Four groups of 8 animals each were fed: (1) a nutritionally adequate diet (C); (2) a 36% ethanol-containing (as percent of energy), isocaloric diet (A); (3) a 2% protein-containing, isocaloric diet (PD); and (4) a 36% ethanol, 2% protein-containing, isocaloric diet (A-PD), respectively, following the Lieber DeCarli model. Ethanol-fed, protein-deficient animals showed the highest liver Fe, and the lowest Zn and Cu values, although differences in liver Zn, Mn, and Cu values were not significantly different between PD and A-PD groups. Statistically significant differences of these parameters were observed between the A and the A PD groups, and between the A and PD groups, except for liver iron. Except for liver Mn, differences between C and A groups were statistically significant. These alterations correlated with liver fibrosis and steatosis, serum albumin, and weight loss, except for liver Mn, which was not correlated with fibrosis or steatosis. Thus, protein deficiency seems to enhance ethanol-induced liver Fe, Zn, and Cu alterations, whereas protein deficiency, but not ethanol, seems to play a major role on liver Mn alterations. PMID- 1418657 TI - An N-hydroxylated derivative of cyanamide that inhibits yeast aldehyde dehydrogenase. AB - A stable, N,O-dibenzoyl derivative (DBHC) of N-hydroxycyanamide, the latter the postulated bioactivation product of the alcohol deterrent agent, cyanamide, has been synthesized. DBHC was an effective inhibitor of yeast aldehyde dehydrogenase (AIDH) in vitro and inhibited this enzyme in a concentration-dependent manner with an IC50 of 25 microM. Hydrolysis of the benzoate moiety of DBHC with dilute NaOH gave rise to the formation of nitroxyl (HN = O), detected by gas chromatography as nitrous oxide (N2O), the end-product of nitroxyl dimerization and disproportionation. It is postulated that the nitroxyl liberated by esterase action on DBHC by yeast AIDH may be the reactive species that inhibits AIDH. PMID- 1418658 TI - Adaptive changes of dopamine-D2 receptors in rat brain following ethanol withdrawal: a quantitative autoradiographic investigation. AB - The effect of subchronic treatment with two doses of ethanol (5 and 10 vol% drinking fluid) on the density of dopamine-D2 receptors was investigated at two different phases of withdrawal, namely 24 h and 5 days after the cessation of the ethanol application. The number of dopamine-D2 receptors was affected in regions receiving projections from both the substantia nigra as well as the ventral tegmentum. Twenty-four hours after the replacement of the ethanol solution by water, a dose-dependent decrease of D2 receptors was found in all regions (N. caudatus dorsalis, medialis and ventralis, N. accumbens lateralis and medialis, tuberculum olfactorium) and most of the analyzed planes [interaural 7.7-10.2 according to the atlas of Paxinos and Watson (35)]. At day 5 of withdrawal, the number of dopamine-D2 receptors of the animals treated with 5 vol% ethanol reached the level of water controls in most planes. In contrast, two- to three fold higher numbers were detected in animals treated with the higher dose. Only in the most caudal parts of the investigated regions, was the number of receptors decreased with the higher dose. The mesocorticolimbic system seems to be less sensitive to the effects of ethanol than the nigrostriatal neurones. The findings of the present study suggest an increased activity of dopaminergic neurons with an adaptive reduction of dopamine-D2 receptors during the subchronic treatment with ethanol during the first day(s) of withdrawal. This phase is followed by a reduced turnover rate for up to 7 days (21). The reduced activity of dopaminergic neurones induces a compensatory increase of the number of receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418659 TI - Cimetidine as a scavenger of ethanol-induced free radicals. AB - Free radical generation and the mobilization of catalytic iron are important in the pathogenesis of alcohol-induced liver injury. Cimetidine is a free radical scavenger in thermal skin injury and cobra venom-induced lung injury, and was therefore investigated as a scavenger of ethanol-induced free radicals. In vitro cimetidine inhibited iron-mediated cleavage of DNA as well as the potentiation of such cleavage by bleomycin. Peroxidation of microsomes by xanthine-xanthine oxidase, acetaldehyde-xanthine oxidase, as well as by the addition of low molecular weight iron chelates were inhibited (17-100%) by cimetidine (0.1-1 mM). Free radical generation due to ethanol in isolated rat hepatocytes was studied by measuring ethane and pentane production. Cimetidine (1 mM) significantly decreased ethane and pentane production due to ethanol: 1 mM (2.2 +/- 0.3 vs. 1.0 +/- 0.2 pmol ethane per 10(6) cells/h; p less than 0.01, 4.2 +/- 0.4 versus 1.6 +/- 0.3 pmole per 10(6) cells/h pentane; p less than 0.001). Similar inhibitions were observed in the isolated perfused liver. Studies of superoxide reduction of ferricytochrome-C as well as hydroxyl radical generation by Fe(+)+/EDTA/ascorbate revealed that cimetidine was an effective hydroxyl radical scavenger. In summary, in a variety of in vitro systems, as well as in isolated hepatocytes and perfused liver, cimetidine inhibits ethanol-induced free radical injury. These findings may warrant its investigation as a therapeutic agent. PMID- 1418660 TI - Binding of serotonergic ligands to brain membranes of alcohol-preferring AA and alcohol-avoiding ANA rats. AB - The alcohol-preferring AA rats have higher concentration of 5-hydroxytryptamine (5-HT) in the brain than the alcohol-avoiding ANA rats. In the present study, the 5-HT1, 5-HT2, and 5-HT3 receptors were studied with [3H]5-HT, [3H]ketanserin, and [3H]LY278584, respectively, in membrane homogenates from different brain regions of both rat lines using in vitro binding assays. No differences in the 5-HT1 and 5-HT2 receptor binding in the brainstem, hippocampus, frontal cortex, and hypothalamus or in the 5-HT3 receptor binding in the nucleus accumbens, amygdala, hippocampus, and frontal cortex were observed between the ethanol-naive animals of the rat lines. In rats given the opportunity to voluntarily consume alcohol, there was a tendency to increase 5-HT1 binding in the ANA rats, which tendency was, however, also found in their ethanol-naive controls subjected to the same handling and behavioral tests as the ethanol-experienced animals. The results do not, however, indicate that any genetic modifications of the 5-HT receptor binding sites have occurred in the process of the selective breeding of AA and ANA rats for alcohol preference and avoidance, respectively. PMID- 1418661 TI - Ethanol intake: effect on liver and brain mitochondrial function and acetaldehyde oxidation. AB - The effect of a chronic ethanol consumption by forcing rats to drink a 20% v/v ethanol solution as sole drinking fluid, for 3 months, was evaluated on: liver and brain mitochondrial function, the capacity of isolated mitochondria to oxidize acetaldehyde, as well as on the low Km mitochondrial AlDH activity, in rats. The O2 uptake by liver and brain mitochondria in the presence of glutamate + malate, succinate or ascorbate + TMPD, was measured polarographically with a Clark electrode. Acetaldehyde oxidation was measured by the disappearance rate in presence of the intact or disrupted mitochondria (AlDH activity) by gas chromatography. Results indicate that an ethanol intake of 11 g/kg b.wt. per day produce a significant reduction of the liver mitochondrial respiration tested with all the substrates used, including acetaldehyde. In contrast, the activity of AlDH in disrupted mitochondria remained unchanged. These results are in accord with the idea that a progressive deterioration of liver mitochondrial function appears with the increase in amount of ethanol consumed, and that alterations of acetaldehyde oxidation by intact mitochondria can be detected before an alteration of the AlDH activity. Concerning the brain, this ethanol consumption regimen did not affect the brain mitochondrial respiration tested with glutamate + malate, succinate or ascorbate + TMPD, but it induces an increase in acetaldehyde oxidation rate by intact brain mitochondria. The imposed increase in the cerebral aldehyde oxidizing capacity could reflect a principal biochemical mechanism underlying neural adaptation to ethanol. PMID- 1418662 TI - Evaluating the palatability of alcohol for rats with measures of taste reactivity, consumption, and lick rate. AB - In two experiments, rats were presented with water and six concentrations of alcohol (0.5%, 3%, 6%, 9%, 12%, and 15%, v/v) under conditions of mild fluid deprivation. Their responses were measured using taste reactivity (fluids infused directly into the mouth), consumption, and lick rate (both in a voluntary drinking situation). Results in both experiments showed that the number of overall ingestive responses was relatively high and consistent across all alcohol concentrations and water; aversive responding was low for all solutions. During one-bottle, 10-min tests, rats consumed the three lowest concentrations of alcohol (0.5%, 3%, and 6%) and water at an equal level. There was an abrupt drop in the amount of alcohol consumed at 9% and a continued decrease at the two highest concentrations. Lick rates for alcohol (measured only in Experiment 2) fell into three general patterns: 0.5%, 3%, and 6% produced almost identical, negatively accelerating curves consistently above that of water which was linear; lick rates for 9% and 12% rose initially but, at approximately 2 min, became flat; the 15% solution produced a low lick rate throughout the 5-min period. There were significant correlations between lick rate and amount consumed but, contrary to expectations, no significant correlations were found between taste reactivity and the other two measures (consumption and lick rate). These results suggest that taste reactivity to alcohol solutions may be reflective of processes different from those that regulate licking behavior or actual consumption. PMID- 1418663 TI - Differential inhibition by ethanol of norepinephrine- and clonidine-induced emesis in cats. AB - The effect of acute ethanol administration into the cerebral ventricles on the unanesthetized cat upon emesis produced by norepinephrine and clonidine injected similarly as well as upon emesis evoked by copper sulfate given orally was compared and investigated. Ethanol inhibited the norepinephrine- and clonidine induced emesis. The inhibitory effect of ethanol occurred after a transient and inconsistent emetic action of the drug. Norepinephrine-induced emesis was about 12 times more sensitive than clonidine-induced emesis to the inhibitory effect of ethanol. In addition, norepinephrine-, but not clonidine-induced emesis was abolished after ablation of the area postrema. On the contrary, intracerebroventricular ethanol had virtually no effect on emesis caused by intragastric copper sulfate. The inhibitory effect of ethanol is ascribed to an action on alpha-2 adrenoceptors within the area postrema and on imidazoline preferring sites and/or muscarinic cholinoceptors outside the area postrema, but not on the emetic region of the brainstem reticular formation. It follows then that ethanol can differentiate alpha-2 adrenoceptors from imidazoline-preferring sites and/or muscarinic cholinoceptors in the brain of the cat. PMID- 1418664 TI - Ethanol decreases progesterone synthesis in human placental cells: mechanism of ethanol effect. AB - Fetal alcohol syndrome (FAS) is a set of signs and symptoms in offsprings born to mothers who abuse alcohol during pregnancy. We postulated that impairment in the placental endocrine function contribute to FAS. In this study, we examined in vitro effects of ethanol on the placental cells' (cytotrophoblast cells) capacity to synthesize progesterone. Cytotrophoblast cells were isolated from normal term placenta and were incubated (2 x 10(6)) with 20-, 30-, and 40-mM doses of ethanol for 6 h. Progesterone was measured in the incubate by RIA. The results showed that, at the 20-mM dose of ethanol, progesterone synthesis was significantly decreased (p less than 0.01), at the 30-mM dose level there was a further decrease of 20%. The differences between 30- and 40-mM ethanol dose levels were not significant. To determine the mechanism of ethanol effects on progesterone synthesis, cytotrophoblast cells were preincubated with 30 mM ethanol followed by 10 microliters of LDL (10 microliters LDL = 80 micrograms cholesterol) and vice versa. The results showed that ethanol effects on progesterone synthesis was dependent on whether ethanol was added prior to or following the addition of LDL in the medium. If ethanol was added in the medium prior to LDL, progesterone synthesis was decreased significantly (p greater than 0.01); however, when ethanol was added after the LDL, ethanol had no effect on progesterone synthesis. In the experiment where ethanol and LDL were added simultaneously in the medium, ethanol blunted the stimulatory effect of LDL on progesterone synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418665 TI - The effect of heparegen on antioxidant enzyme activities in ethanol-induced liver injury in rats. AB - SOD, CAT, GSH-Px, and sulfhydryl compounds MDA contents in liver of rats treated with heparegen for 7, 14, and 21 days after alcoholic liver injury have been investigated. After use of this drug, we found beneficial effects on GSH-Px activity, sulfhydryl compounds (total and nonprotein), and MDA content and a partially beneficial effect on SOD and CAT activities. These enzyme activities after 21 days of drug administration were restored. Furthermore, heparegen shortens the time necessary for the return of AIAT and GGTP to normal value. This enzymatic data are supported by histological studies in light microscopy. PMID- 1418666 TI - Ethanol drinking patterns in a continuous-access operant situation: effects of ethanol concentration and response requirements. AB - Rats, initiated to self-administer ethanol with either a sucrose-substitution procedure or a secondary-conditioning procedure, were maintained in a continuous access environmental system in which operant lever press responses were required to receive 10% ethanol and food reinforcement. Water available from a drinking tube was electronically monitored to detect licks. Total daily consumption and patterns of food, water, and ethanol responding were analyzed under conditions in which the concentration of ethanol presented as a reinforcer was either 10% or 20%, and the response requirement for ethanol reinforcement was either a fixed ratio 4 schedule or a fixed ratio 1 schedule. Either increasing the ethanol concentration or decreasing the response requirement resulted in an increase in total daily ethanol intake. There was no significant difference between initiation procedures. These results are similar to observations in studies using a limited-access operant situation. This increased ethanol intake resulted from a complex alteration in the daily ethanol drinking pattern. The greatest ethanol intakes were observed when both the ethanol concentration was increased and response requirement was decreased. This was predominantly the result of increasing the number of ethanol drinking bouts per day when the response requirement was decreased, and by decreasing individual bout size by less than half when the ethanol concentration was doubled. These studies indicate that concentration of the ethanol presented as the reinforcer and the response cost required for reinforcement are involved in regulating ethanol consumption in the continuous-access condition. Type of initiation did not appear to interact with these variables. PMID- 1418667 TI - Sex differences in pattern of drinking. AB - Drinking patterns of male and female Long-Evans rats were compared during a 15 day drinking period. All animals were tested for preference for alcohol for 24 h during which food, water, and beer containing 5% ethanol were freely available. Animals drinking 50 ml or more of beer were chosen for the experiments. On days 1 5, animals were offered food, water, and beer containing 5% ethanol (v/v). On days 6-15, the concentration of ethanol in the beer was doubled to 10% (v/v). Preference ratios (beer/total fluid) were higher for females than males, and females consumed more grams of alcohol per unit of body weight. When alcohol concentration was doubled, females increased alcohol intake (g/kg), while males tended to titrate alcohol intake to levels consumed at 5% concentration. Female patterns of drinking differed from male patterns of drinking. PMID- 1418668 TI - Gender differences in ethanol oxidation and injury in the rat stomach. AB - A significant fraction of orally consumed ethanol is metabolized by the alcohol dehydrogenase (ADH) enzyme present in the gastric mucosa. Human studies have shown that this "first pass metabolism" of ethanol correlates quite closely with gastric ADH activity which has been demonstrated to be greater in men than women. The present study was undertaken to determine if gender influences the magnitude of ethanol-induced injury in rat gastric mucosa and whether any differences can be linked to altered levels of ADH activity. Since prostaglandins (PGs) have been shown to markedly attenuate the severity of gastric injury induced by ethanol in the rat stomach, a further goal of this study was to determine whether the efficiency of PG's protective action was in any way influenced by gender. Accordingly, both male and female rats were pretreated subcutaneously with 16,16 dimethyl PGE2 (10 micrograms/kg) or saline 30 minutes prior to administering an oral dose of 50% ethanol in saline or saline alone. They were then sacrificed 5 minutes later. In a portion of animals (n = 6 per group), samples of mucosa from the glandular stomach were obtained and kinetic activity of ADH determined. In another portion of animals (n = 6 per group), gastric tissue samples from the glandular mucosa were examined by light microscopy and the magnitude of mucosal injury quantified. Alcohol-treated females showed significantly (p less than 0.05) less superficial and more deep mucosal injury than male counterparts. Further, ADH kinetic activity in female rats was significantly less than that observed in male counterparts of similar weight (83% of males; p less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418669 TI - Prenatal ethanol exposure alters adrenocortical response to predictable and unpredictable stressors. AB - In the present study, effects of psychological stressors and stressor predictability on the adreno-cortical responses of animals exposed to ethanol in utero were examined. Male and female offspring from ethanol-exposed (E), pair-fed (PF), and ad lib-fed control (C) conditions were tested in adulthood. Separate sets of animals were exposed once daily for 5 consecutive days to either unpredictable (UNPRED) or predictable (PRED) restraint stress or to UNPRED novelty stress. On the fifth test day, blood samples for plasma corticosterone determination were taken either prior to stress (basal levels) or following stress. Males in all groups and C females had higher basal corticosterone levels if previously subjected to PRED restraint than if previously subjected to UNPRED restraint; E and PF females did not exhibit this differential responsiveness. Following restraint stress on the fifth test day, there were no significant differences in response to PRED and UNPRED restraint among E, PF, and C males. In contrast, C but not E or PF females exhibited a greater plasma corticosterone response to UNPRED than to PRED restraint. Following novelty stress, E males exhibited a significantly reduced plasma corticosterone response compared to PF and C males. For females, there was a trend for an increased corticoid response in E compared to PF females following novelty stress as well as a different pattern of response among groups from days 1 to 5 of testing. These data support and extend previous studies suggesting that, compared to PF and C animals, E animals may exhibit altered responses to stressors as well as deficits in the ability to use or respond to environmental cues. PMID- 1418670 TI - Effects of morphine on acquisition and maintenance of ethanol and water intake patterns in rats. AB - Two experiments were conducted to assess the effects of chronic subcutaneous injections of morphine (1.0 mg/kg) or saline on the pattern and amount of sweetened ethanol and water intake in fluid restricted Long-Evans rats. Following daily injections, 2-h two-bottle choice tests were conducted with water and an ethanol solution (15% ethanol v/v in 5% sucrose w/v). During a 20-day acquisition phase (Experiment 1), ethanol intake patterns and amounts did not differ between saline (n = 6) and morphine (n = 6) groups. Both groups exhibited ethanol intake patterns that decreased exponentially throughout the session suggesting control by fluid restriction procedures. Morphine decreased water intake during initial periods of each session and increased intake during later periods. In Experiment 2, morphine and saline injections were reversed across three phases with the same rats. Morphine increased total ethanol consumption during the first few days of each 15-day phase, but the groups did not differ thereafter, and the initial increases produced no statistically significant group differences. Additionally, morphine augmented ethanol intake in early portions of sessions, while water intake was decreased and increased during early and later portions of each session, respectively. Analysis of the data from the last 5 days of each phase indicated that, when injected with morphine, the group which received saline during acquisition consumed significantly more ethanol solution than the group injected with morphine during acquisition. The effect on patterns of water and ethanol intake were observed, regardless of the drug injected during acquisition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418671 TI - The limited access paradigm: description of one method. AB - Restricting access to alcohol to a short period daily causes rats, in effect, to drink on command. They usually begin drinking alcohol immediately when it is first made available each day and consume a rather constant amount during each access period. The procedure thus has a variety of useful applications. The specific method reported here in detail provides continual access to food and water, but access to unflavored 10% ethanol solution only 1 h/d, all in the home cage, and produces mean alcohol intakes from 0.5-1.0 g/kg in the access hour. PMID- 1418672 TI - The influence of alcohol and sleep deprivation on stimulus evaluation. AB - The effects of alcohol and sleep deprivation on choice reaction time (RT) as a function of stimulus intensity, stimulus quality, and response compatibility were investigated. Fifty-four male subjects were assigned to one of three levels of alcohol (0.00, 0.07, or 0.10 BAC), and one of two levels of sleep deprivation (0 or 24 h). Stimulus intensity, stimulus quality, and response compatibility were varied (high or low), with RTs identified according to time on task. Significant main effects of each of the stimulus variables were present in baseline analysis, with low-level conditions producing longer RTs. Alcohol produced an overall slowing of RT. The combination of both treatments led to larger increases in RT for low stimulus quality. Sleep deprivation increased RT for high stimulus intensity. Alcohol increased RT for low stimulus intensity, but only when subjects were not sleep deprived. These results imply higher risk with degraded stimulus conditions, e.g., driving in settings of low visibility or at night. PMID- 1418673 TI - Purification and properties of 4-halobenzoate-coenzyme A ligase from Pseudomonas sp. CBS3. AB - The bacterial strain Pseudomonas sp. CBS3 possesses a multi component enzyme system which converts 4-chlorobenzoate to 4-hydroxybenzoate. In the first step 4 chlorobenzoate is activated in a coenzyme A, ATP and Mg(2+)-dependent reaction to 4-chlorobenzoyl-coenzyme A. ATP is cleaved thereby into AMP and pyrophosphate. The involved 4-chlorobenzoate-coenzyme A ligase was purified to apparent homogeneity by a 6-step purification procedure. The native enzyme had an apparent molecular mass of 115000 Da and was composed of two identical polypeptide subunits of 57 kDa. The enzyme displayed an isoelectric point of 5.3. The maximal initial rate of catalysis was achieved in 100mM Tris/HCl or Tricine/NaOH buffer, pH 8.4, at 35 degrees C. Under these conditions the apparent Km values for ATP, coenzyme A and 4-chlorobenzoate were 2.4 to 3.5 mM, 0.11 to 0.19mM and 0.05 to 0.065mM, respectively. Vmax was 111.6 mumol/(min x mg protein). The N-terminal amino-acid sequence was determined. 4-Halobenzoates were preferentially converted to the corresponding thioesters. Therefore, the enzyme was named 4-halobenzoate coenzyme A ligase. PMID- 1418674 TI - Inhibition of human mast cell tryptase by benzamidine derivatives. AB - Considerable circumstantial evidence has been provided by in vitro studies that tryptase (EC 3.4.21.59), a neutral serine proteinase stored in large amounts in mast cell granules, may play an important pathogenetic role in mast cell dependent diseases. However, a definitive role has not yet been ascribed to this trypsin-like enzyme with restricted substrate specificity as natural or synthetic inhibitors of tryptase applicable for in vivo studies are not available so far. Therefore, we have studied structure-activity relationships for inhibition of tryptase by benzamidine derivatives, compounds known to be potent inhibitors of various trypsin-like enzymes. Among the benzamidine derivatives 4 amidinophenylpyruvic acid exerts a striking inhibitory activity with a Ki of 0.71 mumol/l. Several additional inhibitors of tryptase with Ki values in the micromolar range were found among bis-benzamidines. Derivatives of N alpha arylsulfonyl-omega-amidinophenyl-alpha-aminoalkylcarboxylic acids are only weak inhibitors of tryptase, although members of this group are potent and selective inhibitors of several other trypsin-like enzymes. Comparison of the inhibition of tryptase and trypsin revealed that the affinities of the benzamidine derivatives to both proteinases are closely correlated (correlation coefficient r = 0.702; n = 37; p < 0.001). These results demonstrate that 4-amidinophenylpyruvic acid may be useful as a pharmacologic tool for the investigation of the (patho)physiological role of tryptase. In addition, benzamidine derivatives may be applicable to probe the active site topography of tryptase isoenzymes. PMID- 1418675 TI - Amino-acid sequence of the short subfragment-2 in adult chicken cardiac muscle myosin. AB - The amino-acid sequence of the short subfragment-2 in the amino-terminal portion of subfragment-2 derived from adult chicken ventricular muscle myosin was completely determined by direct protein analysis. Peptides fragmented by cyanogen bromide, lysyl endopeptidase and arginyl endopeptidase of S-carboxymethylated S-2 and peptides of large CNBr peptides cleaved by dilute formic acid were separated and sequenced. This short S-2 composed of 259 amino-acid residues was found highly conserved and contained hydrophobic and charged residue repeat units. Comparing this sequence with the partial nucleotide sequence of cDNA corresponding to short S-2 (Stewart A.F.R., et al. (1991) J. Mol. Evol. 33, 357 366), a 64 amino-acid residues extension towards the NH2 terminus and 9 residues differences were observed. Furthermore, this sequence is compared with those of rat, rabbit and human ventricular myosins, and 86.1%, 86.5%, 86.5% sequence identities are observed, respectively. PMID- 1418676 TI - New analogues of Cucurbita maxima trypsin inhibitor III (CMTI III) with simplified structure. AB - Seven new analogues of trypsin inhibitor CMTI III were obtained by solid-phase peptide synthesis. Three analogues contained only two, instead of three, disulfide bridges, whereas the molecules of the next four analogues were shortened at the N- and/or C-terminus. The elimination of one disulfide bridge in CMTI III induces a decrease in the association equilibrium constants by 6-7 orders of magnitude, whereas the removal of one, two or three amino-acid residues at the N- and/or C-terminus does not significantly affect the activity. PMID- 1418677 TI - Dihydropteridine reductase from Escherichia coli exhibits dihydrofolate reductase activity. AB - E. coli Dihydropteridine reductase, known to have a pterin-independent oxidoreductase activity with potassium ferricyanide as electron donor, has now been shown to possess also dihydrofolate reductase activity. The kinetic parameters for dihydrofolate reductase activity have been determined. The ratio of the three activities, dihydropteridine reductase, dihydrofolate reductase and pterin-independent oxidoreductase activity is 1.0, 0.05 and 4.3, respectively. The enzyme, a flavoprotein which is unstable in the presence of dithiothreitol, was shown to be a monomer with a molecular mass of 25.7 kDa. The apparent lack of discrimination between hydride transfer from the pyridine nucleotide to N5 of the pterin in the dihydropteridine reductase reaction and C6 of folate in the dihydrofolate reaction suggested that the FAD prosthetic group may be involved in the hydride transfers. The flavoprotein inhibitor N,N- dimethylpropargylamine inhibited the dihydropteridine reductase and oxidoreductase reactions differently and did not affect the dihydrofolate reductase activity however. PMID- 1418678 TI - Neurohypophysial vasopressin and oxytocin as influenced by (6R)-5,6,7,8 tetrahydro-alpha-biopterin in euhydrated and dehydrated rats. AB - Experiments were performed to test a possible role of (6R)-5,6,7,8-tetrahydro alpha-biopterin dihydrochloride (BH4) in the neurohypophysial vasopressin and oxytocin content in euhydrated and dehydrated rats. Chronic treatment with BH4, administered to not dehydrated animals, was followed by a significant decrease of neurohypophysial vasopressin, but not of neurohypophysial oxytocin. In dehydrated animals the neurohypophysial vasopressin content decreased progressively; this process was not affected significantly by BH4. In rats dehydrated and treated simultaneously with BH4 the decrease of neurohypophysial oxytocin content was distinctly less marked. PMID- 1418679 TI - An investigation into the glycolipid metabolism of alpha-N acetylgalactosaminidase-deficient fibroblasts using native and artificial glycolipids. AB - Deficient activity of lysosomal alpha-N-acetylgalactosaminidase represents a recently recognized lysosomal disorder whose neurologic manifestation in infancy is infantile neuroaxonal dystrophy. The lysosomal enzyme defect, inherited as an autosomal recessive trait, was first identified in the two brothers, GD and BD. Metabolic modification of glycolipids with terminal alpha-GalNAc was studied in fibroblasts from these patients. [Ceramide-3H]Forssman-glycosphingolipid (GSL), the fluorescent C6-NBD-lyso-Forssman-glycolipid (GL) and a 14C-labelled neoglycolipid containing the blood group A trisaccharide were synthesized and used as probes in degradation studies with cell homogenates and with cells in culture. Assays of each of these substrates with fibroblast homogenates of the patients demonstrated the profound deficiency of alpha-N-acetylgalactosaminidase activity compared with controls. Residual activities in the patients' fibroblast homogenates were detected with all glycolipid substrates; those amounted to 6.3 +/- 3.7% (BD) and 12.8 +/- 6.3% (GD) of the mean activity in controls for [3H]Forssman-GSL, and to 2.2 +/- 0.8% (BD) and 3.6 +/- 1.8% (GD) for C6-NBD-lyso Forssman GL, respectively. alpha-N-Acetylgalactosaminidase deficiency in intact cells was confirmed by TLC analyses, which showed impaired glycolipid modification in cell extracts obtained following addition of [3H]Forssman GSL and C6-NBD-lyso-Forssman GL to the culture media of fibroblasts from the patients. PMID- 1418680 TI - Prostaglandin D2 and E2 syntheses in rat Kupffer cells are antagonistically regulated by lipopolysaccharide and phorbol ester. AB - Prostaglandin-synthesizing activities were demonstrated in cell-free extracts of rat Kupffer cells and characterized. The enzymatic properties of PGH2 synthase were found to be similar to those of synthases present in other organs or cell types. The specific activity of the enzyme was not changed by substances that stimulate prostanoid release by intact Kupffer cells; however, it was reduced by pretreatment of the cells with glucocorticoid hormones. On the other hand, the activities of PGD2 and PGE2 synthase were influenced differently by the kind of cell stimulation. While pretreatment of the intact cells with endotoxin and/or inhibition of protein kinase C led to an enhanced PGE2 formation in cell-free extracts, exposure to agents that enhance protein kinase C-dependent signalling pathways, e.g. phagocytotic stimuli or phorbol ester, suppressed PGE2 synthase activity and, therefore, led to enhanced PGD2 synthesis. It is in line with this observation that in vitro activation of protein kinase C of Kupffer cells resulted in a reduced PGE2 and an enhanced PGD2 synthase activity. PMID- 1418681 TI - Isolation and characterization of a non sex-specific lipoprotein from hemolymph of fresh water crab Potamon potamios. AB - A non sex-specific high density lipoprotein (HDL) was isolated from the hemolymph of male fresh water crab Potamon potamios. Antiserum against male lipoprotein precipitated a lipoprotein from ovigerous and non ovigerous females. The lipoprotein was isolated by a combination of KBr density gradient ultracentrifugation and gel filtration on Bio-Gel A-1.5m. Two yellow bands with hydrated density of 1.08 and 1.10 g x ml-1 were observed following density gradient ultracentrifugation. Native polyacrylamide electrophoresis showed a low- and a high-mobility band, staining with Sudan black. Both native bands were resolved to a single 128 kDa band in SDS-PAGE. The relative molecular masses of the two bands, as determined by gel filtration and native gradient gel electrophoresis, were 230 and 440 kDa, respectively. Since the lipid content was 50% and the molecular mass of the apoprotein was 128 kDa, we suggest that the lipoprotein is a monomer and a dimer. Chemical cross-linking experiments support this observation. The isoelectric point of the lipoprotein was pH 5.8. The amino acid composition was also determined. The lipoprotein contained 50% lipids, with phospholipids being the predominant species (80%). Phosphatidylcholine (66%) and phosphatidylethanolamine (16%) were the predominant phospholipids. The fatty acid content of the lipoprotein was also determined. The lipoprotein contained 68% unsaturated fatty acids with oleate being the dominant species (35%). PMID- 1418682 TI - Secondary fungal metabolites and their biological activities, II. Occurrence of antibiotic compounds in cultures of Armillaria ostoyae growing in the presence of an antagonistic fungus or host plant cells. AB - We found that in the presence of host plant cells or some antagonistic fungi, the highly forest-pathogenic basidiomycete Armillaria ostoyae is strongly stimulated to produce a series of toxic secondary metabolites which are capable of inhibiting the growth of the antagonist or of killing the plant cells still before cell contact. The chemical structures of the metabolites have been identified, of which two of them are new compounds. The time dependence and sites of synthesis in the mycelium have been determined in order to lay the foundation for future studies concerning the induction mechanism for the synthesis of the toxins. PMID- 1418683 TI - Isolation and partial characterization of the outer dense fiber proteins from human spermatozoa. AB - Flagella of human spermatozoa were separated from the sperm head by sonication at 25 kHz and subsequent density gradient centrifugation in Percoll. For isolation of the outer dense fibers (ODF), the flagellar membrane and fibrous sheath were dissolved under reducing conditions in the cationic detergent cetyltrimethylammonium bromide (CTAB) for 30, 60 and 90 min, respectively. The isolation steps were monitored by phase-contrast microscopy and electron microscopy. After SDS-PAGE and silver staining two protein bands at 55 and 67 kDa could be detected. An identification of these proteins as phosphoproteins, either with molybdate/methylgreen or rhodamine B, was not possible. The obtained results indicate that the ODF proteins might have more passive elastic than active function with respect to motility of spermatozoa. PMID- 1418684 TI - The enzymatic and release characteristics of sheep neutrophil elastase: a comparison with human neutrophil elastase. AB - Sheep are often used to study tissue damage following shock after traumatic injury and in the course of other diseases. The processes involved are thought to be caused at least in part by elastase released from polymorphonuclear leukocytes (PMNs). Since little is known about elastase and its role as a mediator of tissue damage in sheep, we studied the biochemical properties and release characteristics to sheep leukocyte elastase (SLE) in comparison of those of human leukocyte elastase (HLE). Both enzymes showed similar molecular masses, amino acid compositions, N-terminal amino-acid sequences, and abilities to digest elastin substrates. Differences, however, were found in kinetic parameters measured with the elastase-specific substrate N-methoxysuccinyl-(L-alanyl)2-L prolyl-L- valine-4-nitroanilide (MeoSuc-AAPV-pNa). The Michaelis constant (Km) of ovine elastase was nearly 10 times higher (1.82 mM) than the Km of HLE (0.21 mM). Values of SLE calculated for kcat were 70% and for kcat/Km 8% of corresponding values determined for HLE. In addition, significant differences between sheep and human PMNs were found in in vitro stimulation experiments. In contrast to human PMNs, sheep neutrophils released no active elastase, and only 50 to 70% of the H2O2 produced by human PMNs. This failure to release active elastase could not be explained by a lower elastase content of sheep PMNs, as there were no significant differences found between the elastase contents of sheep and human PMNs. We conclude that elastase liberated by stimulated sheep PMNs is inactivated by a concomitantly released proteinase inhibitor also located within the sheep PMNs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418685 TI - Microbial metabolism of quinoline and related compounds. XV. Quinoline-4 carboxylic acid oxidoreductase from Agrobacterium spec.1B: a molybdenum containing enzyme. AB - The quinoline-4-carboxylic acid oxidoreductase from Agrobacterium spec.1B was purified 84-fold to apparent homogeneity with 15% recovery, using ammonium sulphate precipitation, heat precipitation, hydrophobic interaction, anion exchange- and gel chromatography. The molecular mass of the native enzyme was estimated to be 320 kDa by gel filtration. SDS-polyacrylamide gel electrophoresis of the enzyme revealed three protein bands corresponding to 85, 35 and 21 kDa. Per molecule the enzyme contains 8 atoms of iron, 8 atoms of acid-labile sulphur, 2 atoms of molybdenum, 2 molecules of FAD and as molybdenum cofactor, molybdopterin cytosine dinucleotide. Besides quinoline-4-carboxylic acid the enzyme also catalysed the conversion of quinoline, 4-chloroquinoline and 4 methylquinoline to the corresponding 2-oxo-1,2-dihydroderivatives. Cyanide, methanol, 4-chloromercuribenzoate and acriflavin were effective inhibitors. PMID- 1418686 TI - Anisoosmostic liver perfusion: redox shifts and modulation of alpha ketoisocaproate and glycine metabolism. AB - 1) In isolated perfused rat liver, 14CO2 production from [1-14C]alpha ketoisocaproate or [1-14C]glycine as well as ketogenesis from alpha ketoisocaproate were stimulated upon exposure to hypoosmotic perfusion media, whereas hyperosmotic exposure inhibited. The effects of anisotonicity were preserved when ketogenesis from alpha-ketoisocaproate and 14CO2 production from [1-14C]glycine were already stimulated by glucagon. On the other hand, ketogenesis from tyrosine (2 mM) or octanoate (0.1 mM) were almost unaffected by anisoosmotic exposure. 2) With all ketogenic substrates studied, hypoosmotic (hyperosmotic) cell swelling (shrinkage) decreased (increased) the beta hydroxybutyrate/acetoacetate ratio in effluent perfusate. A shift of the mitochondrial and cytosolic NADH systems to a more oxidized (reduced) state following hypoosmotic (hyperosmotic) exposure was also found upon infusion of beta-hydroxybutyrate/acetoacetate and lactate/pyruvate as redox indicator metabolite couples. The effects of anisotonicity on the beta hydroxybutyrate/acetoacetate ratio were reversible upon normoosmotic reexposure and persisted throughout anisoosmotic exposure despite completion of volume regulatory K+ fluxes within 10-15 min. Hepatic oxygen consumption decreased by about 10% during hyperosmotic cell shrinkage and was transiently stimulated during hypoosmotic exposure. 3) There was a close relationship between ketogenesis from alpha-ketoisocaproate (0.5 mM) and the mitochondrial redox state, as assessed by the beta-hydroxybutyrate/acetoacetate ratio in effluent, regardless of whether the pathway was modulated by anisotonicity or glucagon. 4) Isoosmotic cell swelling induced by addition of glutamine (3 mM) was without significant effect on ketogenesis from octanoate and stimulated ketogenesis and 14CO2production from [1-14C]alpha-ketoisocaproate only slightly (i.e. by less than 10%); however, in each case the hydroxybutyrate/acetoacetate ratio in effluent perfusate decreased by about 20% upon addition of glutamine. 5) Stimulation of 14CO2production from [1-14C]glycine by hypoosmotic exposure and glucagon was only slightly affected when the accompanying decrease of the beta hydroxybutyrate/acetoacetate ratio was reversed by addition of beta hydroxybutyrate. 6) The data are compatible with a hypotonicity (hypertonicity) induced shift of the mitochondrial NADH system to a more oxidized (reduced) state, probably due to a alterations of respiration. Mitochondrial swelling probably also occurs under the influence of glutamine. Modulation of ketogenesis from alpha-ketoisocaproate, but not of glycine oxidation by anisoosmotic exposure and glucagon can be related to the accompanying redox shifts. The observations support the concept that cell volume may be an important parameter determining liver cell function. PMID- 1418687 TI - Development and optimization of an enzyme-linked immunosorbent assay employing two murine monoclonal antibodies for absolute quantitation of human beta glucuronidase. AB - We have developed and optimized an enzyme-linked immunosorbent assay (ELISA) for absolute quantitation of human beta-glucuronidase. This is a double antibody sandwich system employing two murine monoclonal antibodies specific for human beta-glucuronidase developed in our laboratories. The method involves (a) coating of the high binding polystyrene microtitration plate with the first antibody (7B6 IgG), (b) blocking of remaining active sites with 3% bovine serum albumin in phosphate-buffered saline, (c) application of samples, (d) addition of the biotinylated second antibody (6D2 IgG), (e) addition of streptavidin-horseradish peroxidase, and (f) development of color with o-phenylenediamine dihydrochloride H2O2 and reading in a microplate reader at a wavelength of 490 nm. The method is highly sensitive with an optimal range of 10 to 100 ng/ml of the enzyme and is reproducible with intraday and interday precisions of 3.2 and 4.1%, respectively. The enzyme contents of 20 urine and 20 bile samples quantitated by this ELISA method were, respectively, 148 +/- 101 and 6380 +/- 3780 ng/ml (means +/- SD) which correlated well with their enzyme activities. Such a method for absolute quantitation of human beta-glucuronidase is essential for studying its pathophysiologic roles in cholelithiasis and carcinogenesis and can also be used clinically as an indicator for tissue damage or malignancy. PMID- 1418688 TI - Enzymatic properties of polyethylene glycol-modified cholesterol esterase in organic solvents. AB - The solvent dependency and substrate specificity of polyethylene glycol (PEG) modified cholesterol esterase (CEH) catalyzing cholesterol ester synthesis in organic solvents were studied. When cholesterol and linoleic acid were used as the substrates, PEG-modified CEH synthesized cholesterol linoleate only in water immiscible organic solvents. Among some solvents capable of solubilizing all of the reaction components (PEG-modified CEH, cholesterol, and linoleic acid), chloroform was most suitable for enzymatic cholesterol linoleate synthesis, and the synthetic activity for cholesterol linoleate decreased in the order chloroform, benzene, toluene, and cyclohexane. PEG-modified CEH synthesized various cholesterol esters with significant substrate specificity. The substrate specificity for cholesterol ester synthesis in benzene was analogous to that for cholesterol ester hydrolysis in aqueous solution. PMID- 1418689 TI - Partial purification and immobilization of ribonuclease T2. AB - A simple procedure, consisting of water extraction, heat treatment at pH 2.0, negative adsorption on DEAE-cellulose at pH 4.9, and concanavalin A-Sepharose chromatography, was developed for the partial purification of ribonuclease (RNase) T2 from taka-diastase powder with an overall yield of 5.5%. The partially purified enzyme when coupled to aminoethyl Bio-Gel P-60, retained 12-16% of the activity of the soluble enzyme. Temperature stability studies on RNase T2 bound to matrices, activated with increasing concentrations of glutaraldehyde, and the influence of lysine modification on the activity of the soluble enzyme revealed that the low activity observed for the gel-bound enzyme is probably due to the masking of the active site of the enzyme as a result of the involvement of lysine residues, situated near the active site, during coupling. Immobilization did not affect the pH and temperature optima of RNase T2. On repeated use, the bound enzyme retained approximately 55% of its initial activity after six cycles. These results are discussed, taking into consideration the factors affecting immobilized enzymes. PMID- 1418690 TI - Cloning and expression of the Erwinia herbicola tyrosine phenol-lyase gene in Escherichia coli. AB - The tyrosine phenol-lyase (TPL) gene of Erwinia herbicola was cloned and expressed in Escherichia coli, and the complete nucleotide sequence of the gene determined. The TPL gene comprises 1368 bp, encoding 456 amino acids which have 90% amino acid identity with TPL from Citrobacter freundii. After replacing the 5'-flanking region of the TPL gene with the E. coli lac promoter, TPL protein could be hyperproduced constitutively in E. coli without induction by L-tyrosine. PMID- 1418691 TI - Adverse effects of cancer chemotherapy. An overview of techniques for avoidance/minimisation. PMID- 1418693 TI - Adverse effects of diuretics. AB - Analysis of the available evidence indicates that diuretics do not increase coronary heart disease morbidity and mortality. The multiclinic trials supporting the cardiotoxicity hypothesis are few in number and flawed in design. The majority of the trials, including the well designed trials, indicate no excess of coronary heart disease (CHD) events in diuretic-treated patients compared with those given other drugs or placebo. Recent studies indicate no increase in cardiac arrhythmias after diuretic treatment. Also, although depletion of intracellular potassium and magnesium occurs in patients with congestive heart failure even without diuretics, intracellular concentration of these ions is not significantly reduced by diuretics in patients with uncomplicated hypertension. Modest elevations of serum cholesterol may occur during the first 6 to 12 months of treatment with thiazide diuretics. However, after this time these elevations fall to or below the pretreatment level. The fall may be greater in patients receiving other drugs but the differences are small and their clinical significance is questionable. The incidences of hyperglycaemia and diabetes were only minimally increased in long term clinical trials while the importance of hyperinsulinism and insulin resistance in causing CHD remains unproven in patients. Thiazides remain, therefore, a safe and effective treatment for patients with hypertension. PMID- 1418694 TI - Handling of cytotoxic drugs by healthcare workers. A review of the risks of exposure. AB - Increasing utilisation of chemotherapeutic agents in treating patients with malignancy has led to the potential for widespread exposure of healthcare workers who come into contact with patients or these agents in the work place. Unfortunately, these drugs are toxic to both the abnormal and normal somatic cell. This occurs in the patient, and is also likely to affect any individual exposed. There appear to be widely divergent opinions concerning the extent of hazard of coming into contact with these agents, in spite of which caution and minimising exposure risk seems only prudent and appropriate. PMID- 1418695 TI - Acute ketotifen overdosage. A review of present clinical experience. AB - Ketotifen (Zaditen) is a widely used prophylactic antiasthmatic drug with pronounced antianaphylactic properties and a specific H1-antihistaminic effect. This article summarises the available information on acute overdosage of this drug, which was reported in 13 adults and 8 children. The symptoms of acute overdosage observed with ketotifen are similar to those described for antihistaminic agents. However, it would appear that the acute toxicity of ketotifen is rather low, since no serious effects have been reported either in children or in adults after the intake of up to 20mg of ketotifen, which is 10 times the recommended dose. No lethal outcome of acute overdosage has been described in association with this drug. Ketotifen seems to be better tolerated in children than in adults. Based on present clinical experience, management of acute overdosage includes gastric lavage within 2 to 4h after ingestion or activated charcoal after this period. Symptomatic treatment is indicated if arrhythmias, hypotension or seizures develop, and the patient should be kept under surveillance for at least 6 to 8h. PMID- 1418696 TI - Risks versus benefits of withdrawing antihypertensive therapy. PMID- 1418692 TI - Adverse drug reactions to systemic antifungals. Prevention and management. AB - Systemic administration of antifungal agents for invasive mycoses has dramatically increased over the past 10 years in many fields of medicine. The increase has been due both to an increasing immune compromised population and to potent antibacterial agents which allow these fungi to invade tissue. It is apparent that our understanding of the use of both the old and new antifungal agents has significantly increased in the last few years. In this review, we attempt to document our extensive knowledge of the adverse effects of the polyenes, flucytosine, griseofulvin and azoles when given systemically for treatment. Interwoven in this documentation of the adverse reactions to these agents is the attempt to help clinicians potentially avoid some of these adverse effects and if they do occur, to be able to identify and successfully manage them. PMID- 1418697 TI - Protein calorie malnutrition and cancer therapy. AB - Anorexia and cachexia frequently complicate the late stages of malignancy and may be a prominent feature of early disease. The resulting weight loss often becomes a major focus of concern for the patient and the family and may significantly add to the morbidity and mortality of cancer. Factors which contribute to the wasting syndrome include the effects of the tumour, effects of chemotherapy, abnormalities of carbohydrate, fat and protein metabolism and the cytokine response. Administration of total parenteral nutrition (TPN) is an important method of addressing malnutrition, particularly in patients with nonfunctioning gastrointestinal tracts. A critical review of the TPN cancer literature is provided along with a discussion of new approaches and future directions in the nutritional support of patients with malignant disease, such as anabolic agents, hydrazine sulfate and megestrol. PMID- 1418698 TI - Clinical toxicity of interleukin-2. AB - Interleukin-2 (IL-2) is increasingly used to treat patients with cancers refractory to conventional treatment. Flu-like syndromes are extremely frequent but usually mild. A variety of skin complications (mostly erythema and mucositis) have been reported. Life-threatening skin reactions have also been described. Acute reactivation of psoriasis can also occur. Immediate hypersensitivity reactions have so far not been described, but IL-2 treatment has been shown to predispose to acute hypersensitivity reactions to iodine-containing contrast media. Hypothyroidism is the major endocrine complication and antithyroid antibodies have been detected in approximately 50% of patients. Neurological and psychiatric disturbances with moderate or severe mental status changes are common and sometimes treatment-limiting. The occurrence of peritumoural oedema in patients with brain metastases can also be a major practical problem. Musculoskeletal disorders are transient and resolve spontaneously. The vascular leak syndrome is the most frequent and severe complication of IL-2 of which weight gain, generalised oedema, hypotension and impaired renal function are the main features. Even though a damaging effect on vascular endothelium cells by various cytokines released by activated lymphoid cells or mediated by non lymphocyte-dependent factors has been proposed to be involved, the mechanism remains unclear. Other cardiovascular injuries, possibly life-threatening, including myocarditis, angina pectoris and myocardial infarction, can occur during the first days of treatment. Supraventricular arrhythmias are the most common rhythmic disorder. Decreases in myocardial contractility and haemodynamic pattern similar to those of septic shock have been encountered in most cases. Acute renal dysfunction is common but resolves with symptomatic management. Intrahepatic cholestasis with hyperbilirubinaemia is observed in most patients but permanent liver damage has not been described. Several cases of pancreatitis have been reported. Anaemia, thrombocytopenia, lymphocytopenia and eosinophilia are frequent and occur in most if not all patients. Some data suggest a high incidence of infectious complications, particularly in patients with surgically tunnelled catheters, but marked flu-like syndromes may be confounding. Finally, death directly related to IL-2 treatment has been noted in less than 1% of all patients. Investigations are under way to minimise IL-2 toxicity with varying dose regimens and combined treatments. PMID- 1418700 TI - Neuropsychiatric reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). The New Zealand experience. AB - The New Zealand Medicines Adverse Reactions Committee has been monitoring reports of adverse drug reactions (ADRs) since 1965. We wished to determine the numbers of voluntary reports of different types of ADR to all nonsteroidal anti inflammatory drugs (NSAIDs) over a long time period and relate these to age. As the elderly are known to suffer from neuropsychiatric adverse effects of many drugs, we investigated neuropsychiatric reactions to NSAIDs to determine whether these were more commonly reported in the elderly. We counted all reported ADRs suspected to be associated with NSAIDs as well as selected types of ADRs reported from 1970 to 1989. These were divided into 5-year periods and 10-year age groupings. In each consecutive 5-year period there was a progressive increase in the numbers of all ADRs reported for all NSAIDs. This was particularly marked above 50 years of age, but the numbers were reduced above 80 years. Reports for females accounted for about two-thirds of all reactions. Not unexpectedly, alimentary and dermatological ADRs accounted for most reactions and were more common in the group above 50 years. Overall, neuropsychiatric reactions were the third most common ADR type reported. Their numbers increased with age and peaked in the 50 to 59 age group, with a sharp decline after 69 years. This age distribution paralleled that for all ADRs to NSAIDs. Although neuropsychiatric reactions to NSAIDs were reported in all age groups, they were not reported more commonly in the elderly. This study suggests that neuropsychiatric reactions to NSAIDs may be more frequent than is commonly believed. PMID- 1418702 TI - B-cell activation. AB - Extraordinary progress has been made in refining our understanding of the B-cell antigen receptor complex, the role of protein-tyrosine phosphorylation as the key intermediary in immunoglobulin signal transduction, and in identifying candidate effectors of immunoglobulin-mediated signaling. In addition, the properties of a new group of G proteins may rekindle interest in older observations implicating such molecules as important in B-cell activation. PMID- 1418701 TI - New insights into T-cell antigen receptor structure and signal transduction. AB - Recent studies have provided insights into how the complex structure of the T cell antigen receptor relates to its signal transduction function. Both the CD3 and zeta subunits contain functioning signaling modules that regulate the activation of tyrosine kinases and phosphorylation of cellular substrates. PMID- 1418703 TI - Signal transduction by T- and B-cell antigen receptors: converging structures and concepts. AB - Recent evidence demonstrates that the antigen receptor complexes of T and B lymphocytes are very similar in general architecture and primary and secondary structure of component polypeptides, and that they use common mechanisms for transmembrane signal transduction. Most importantly, multiple subunits of each receptor (Ig-alpha, Ig-beta and Ig-gamma, CD3 gamma, CD3 delta and CD3 epsilon, and T-cell receptor zeta and eta) possess a motif of approximately 26 amino acids, denoted ARH1, which appears to carry sufficient structural information for receptor-mediated lymphocyte activation. PMID- 1418704 TI - Costimulation of T-cell growth. AB - The specificity of T-cell recognition is dictated by the interaction of the T cell receptor with MHC-peptide complexes. The biological consequences of such recognition is determined, however, by costimulatory pathway(s). Recent studies have led to the identification of receptor-counter-receptor pairs that may regulate T-cell costimulation. PMID- 1418705 TI - Interleukin-2. AB - In the past year there have been significant advances in understanding the role of interleukin-2. Its role in the activation of T cells by antigen-presenting cells, the structure-activity relationships between interleukin-2 and its receptor and the subsequent signaling have all become clearer. The creation of mice with a specific defect in the interleukin-2 gene has given us a clearer idea of its role in vivo. Recent studies also suggest that interleukin-2 may finally find a role in immunotherapy. PMID- 1418706 TI - Mechanisms of lymphocyte homing. AB - The initiation and maintenance of an effective immune response requires the coordinated function of spatially distinct compartments of the immune system. Such coordination is critically dependent on mechanisms of lymphocyte homing and recirculation. The past year has been significant progress in our understanding of both the molecular basis of these homing mechanisms, and their potential physiological consequences. PMID- 1418699 TI - Adverse effects of general anaesthetics. AB - This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis. PMID- 1418707 TI - Lymphocyte homing to sites of inflammation. AB - The identification by monoclonal antibodies and gene cloning of the major receptors, the integrins, selectins and endothelial adhesion molecules, involved in lymphocyte adhesion and migration has advanced our understanding of the molecular interactions between lymphocytes and endothelial cells in the past few years. These antibodies and soluble receptors are being applied as reagents for studying the in vivo expression of adhesion molecules, the importance of which in various types of inflammation is being recognized. PMID- 1418708 TI - The interleukin-4 family of lymphokines. AB - Evidence has accumulated indicating that four T-cell derived lymphokines, interleukin-4, interleukin-5, granulocyte-macrophage colony stimulating factor and interleukin-3, are closely related. The genes encoding these lymphokines are clustered within a region of 1000 kb, the proteins have a common secondary and spatial organization, and their corresponding receptors are all members of the haemopoietin family of receptors. PMID- 1418709 TI - Interleukin-5. AB - Interleukin-5 is a dimeric cytokine that controls the differentiation of B cells into antibody-secreting cells as well as inducing the growth of Ly-1(CD5)+ B cells and B-cell tumors. It also has a major role of the growth and differentiation of eosinophils. Rapid progress has been made during the last year in the delineation of the structure and activities of interleukin-5, and the molecular nature of its functional receptors. Interleukin-5 exerts pleiotropic activities on various target cells through a high-affinity receptor which is composed of two different polypeptide chains, alpha and beta. The alpha chain binds interleukin-5 with low affinity and the beta chain has been identified as the interleukin-3 receptor-like protein and is also the beta chain of the granulocyte-macrophage colony stimulating factor receptor. PMID- 1418710 TI - Mechanisms of soluble mediators. AB - A two chain model, composed of ligand-binding and signal transducing subunits, first identified in the interleukin-6 receptor system, has been revealed in several other cytokine systems. Common signal transducers shared by several receptor systems may explain a functional redundancy characteristic of cytokines. The signaling pathway from the receptor to gene activation is now becoming clearer due to the successful molecular cloning of several transcription factors. PMID- 1418711 TI - Interleukin-10. AB - Despite the short history of interleukin-10, accumulated evidence indicates that this interleukin plays a major role in suppressing immune and inflammatory responses. Yet interleukin-10 also maintains cell viability and acts as a cofactor to promote the growth of lymphoid and myeloid cells in vitro. Here we review the present knowledge on the structure and function of interleukin-10. PMID- 1418712 TI - Interferon-gamma. AB - During the past year, the most striking progress in our understanding of interferon-gamma has been made in the elucidation of the three-dimensional structure of the molecule and in the analysis of the molecular structure and the functional domains of the interferon-gamma receptor. A greater insight into the molecular mechanisms of gene activation by interferon-gamma has been gained, and the immunoregulatory role of interferon-gamma has been better defined in studies dealing with its effects on B-cell function and with its production by the various T-cell subsets. Finally, the effects of interferon-gamma on intracellular parasites is an important aspect of interferon-gamma activity that is giving rise to several clinical trials. PMID- 1418713 TI - T helper cells. AB - B-cell proliferation and differentiation is controlled by T helper cells. Recent studies have determined that the expression of a novel, 39 kD, T-cell membrane protein is responsible for inducing T-cell-dependent B-cell activation. The receptor for this protein on the resting B cell is CD40. Once activated, B cells are induced to grow and differentiate by the elaboration of interleukin-4 and interleukin-5 from activated T cells. Together, T cell-B cell contact and soluble factors provide all the signals required for B-cell growth and differentiation. PMID- 1418714 TI - Cell-mediated cytotoxicity. AB - Progress is being made in determining how cytotoxic cells are activated, the way the lethal hit is delivered and the subsequent events in the target cell. Several factors cloud the issue, including the heterogeneity of cytotoxic cells, differences between fresh cells and cell lines, and the possibility of single cells using multiple cytotoxic mechanisms. The most difficult task will be to define which cytotoxic mechanisms are significant in vivo. PMID- 1418716 TI - Lymphocyte activation and effector functions. PMID- 1418715 TI - Macrophage activation by T cells. AB - In the past year, the application of biochemical and molecular approaches to the analysis of macrophage activation by T cells has provided new information concerning the regulation of gene expression during the activation process, and advanced our understanding of the multiple mechanisms that influence the development of macrophage function during an immune response. PMID- 1418717 TI - Inhibition of immune induction: the target of current transplantation tolerance strategies. PMID- 1418718 TI - Immunosuppressive therapy. AB - Although Cyclosporin A has improved transplant outcome, its use has serious limitations due to its narrow therapeutic window. New approaches to broaden this window exploit alternative drug formulations, pharmacokinetic profiling and new immunosuppressive agents, such as Rapamycin and Brequinar, which act in a synergistic fashion. There is no evidence to suggest that the pharmacological alternative to Cyclosporin A, FK-506, displays a broader therapeutic window, although it may be tenfold more potent. Similarly, despite the specificity of the IgG2a mouse anti-human CD3 monoclonal antibody, it displays a significant range of clinical side effects, delayed therapeutic action and frequently stimulates generation of human anti-mouse monoclonal antibodies. Recent advances in monoclonal antibody technology seek not only to produce antibodies against determinants involved in alloactivation, but also to 'humanize' the antibodies for reduced side effects. The availability of this array of potential agents highlights the need to develop guidelines for clinical trial methodologies to address the unique needs and demands of organ transplantation. PMID- 1418719 TI - Cellular mechanisms of rejection. AB - Studies by molecular biologists, protein chemists and cell biologists are rapidly providing new tools and information for those interested in the cellular mechanisms of graft rejection. Despite these contributions, a clear picture of the mechanisms involved in rejection has not yet evolved. However, whole new areas for research have developed, providing opportunities for new insights as well as therapeutic interventions. PMID- 1418720 TI - The use of colony stimulating factors in clinical bone marrow transplantation. AB - The use of colony stimulating factors in clinical bone marrow transplantation is rapidly evolving. Both granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor have shown efficacy in bone marrow transplant patients in accelerating the rate of myeloid recovery. The use of colony stimulating factor primed peripheral blood progenitor cells appears to accelerate platelet recovery as well as myeloid recovery. PMID- 1418721 TI - Graft versus host disease following allogeneic bone marrow transplantation. AB - Graft versus host disease is a major barrier in allogeneic bone marrow transplantation. The associated morbidity and mortality need to be understood and prevented if possible, as the potential indications for bone marrow transplantation continue to broaden. Areas of investigation include the cellular effector arm as well as the cytokines associated with the expression of the disease. PMID- 1418722 TI - Organ acceptance and rejection. AB - During the past year, transplantation scientists have continued the quest for their version of the Holy Grail, developing and expanding model systems aimed at improving allograft survival. The highlights include further analyses of tolerance induction by intrathymic inoculation of allogeneic tissue, the use of oral tolerance to MHC antigens to improve graft survival, and expansion of the model of bone marrow transplantation to achieve solid organ tolerance in a large animal model and humans. Immunogeneticists have provided data on improved graft survival when MHC matching was performed at the molecular level. PMID- 1418723 TI - Cytokines in rodent reproduction and the cytokine-endocrine interaction. AB - Insights derived from recent studies employing rodent models demonstrate that the synthesis of pluripotent cytokines is an important function of resident cells in the female reproductive tract. Through steroid hormone regulated secretion of these mediators, resident cells appear to coordinate the recruitment and action of leukocytes that are centrally implicated in the dramatic remodelling processes characteristic of reproductive events. PMID- 1418724 TI - Immunobiology of pregnancy. AB - This report presents new findings on two conditions that permit genetically disparate tissues to coexist during pregnancy: (a) regulation of major histocompatibility genes in placental trophoblast, and (b) synthesis of uterine and placental polypeptide growth factors with immunosuppressive properties. Recent experiments examining inter-relationships between these two protective mechanisms are cited, and potential explanations for trophoblast resistance to factors with MHC-inducing properties are proposed. PMID- 1418725 TI - Vaccines against fertility. AB - The first evidence for the efficacy of a birth control vaccine in humans is now available from the Phase II trials on the human chorionic gonadotrophin vaccine in India. Several sperm antigens have been identified as potential contraceptive immunogens and zona pellucida antigens have been reported that reversibly control fertility. PMID- 1418726 TI - Tumor immunology: the first century. PMID- 1418727 TI - Molecular definition of tumor antigens recognized by T lymphocytes. AB - Several tumor antigens recognized by T cells have now been identified at the molecular level. Various mechanisms can account for their expression: activation of normally silent genes; point mutations; chromosome translocations; and post translational modifications of proteins. This led to the notion that potential tumor-rejection antigens can be shared by a significant proportion of human tumors. This may have important implications in cancer immunotherapy, especially since tumors expressing a defined antigen can be identified on the basis of the expression of the relevant gene. PMID- 1418728 TI - MHC antigens and cancer: implications for T-cell surveillance. AB - Evidence for a direct involvement of cell-mediated immune mechanisms in the control of human tumours remains sketchy. The past year, however, has seen advances in our understanding of the relationship between the immune system and tumour cells, and has given rise to new prospects for immunological treatment and the prevention of cancers. PMID- 1418729 TI - New strategies for active immunotherapy with genetically engineered tumor cells. AB - While previous tumor vaccine strategies have shown intriguing results, clearcut efficacy has been difficult to establish in human trials. Recently, newer approaches have been developed in animal systems that modify tumor cells genetically so that they express new antigens or secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects without producing significant systemic toxicity. In addition to local inflammation, this approach can alter the presentation of tumor antigen or activation of tumor antigen-specific T lymphocytes, resulting in systemic antitumor immunity. PMID- 1418730 TI - Construction of cancer vaccines with carbohydrate and protein (peptide) tumor antigens. AB - Tumor vaccinology is as old as immunological thought and as young as our rapidly evolving understanding of antigen processing and presentation. The recent availability of carbohydrate and peptide tumor antigens suitable for vaccine construction, conjugate and recombinant vector technologies capable of augmenting helper and cytotoxic T cell activity and potent new immunological adjuvants have combined to produce considerable optimism for the future of tumor vaccines. PMID- 1418731 TI - Immunogenetics of cell surface antigens of human cancer. AB - Hybridoma technology, immunohistochemistry and molecular genetic techniques have paved the way for a general serological mapping of molecules expressed on the surface of normal and neoplastic cells. The emerging findings challenge cell lineage-based models of differentiation and point to new, modular concepts to explain complex tumor phenotypes. In parallel studies, the repertoire of T-cell recognized tumor antigens--still mysterious but probably quite distinct from the antibody-defined repertoire--has also become accessible to molecular analysis. PMID- 1418732 TI - Monoclonal antibodies in the study and therapy of hematopoietic cancers. AB - Recent advances utilizing monoclonal antibodies to phenotype acute leukemias have revealed no prognostic significance of the expression of lymphoid-associated antigens by acute myeloid leukemia blasts and conflicting results regarding 'biphenotypic' acute myeloid leukemia. Several studies treating patients with refractory lymphoma with immunotoxins reported encouraging results but significant production of anti-mouse or anti-toxin antibody. Radiolabeled antibodies that react with panhematopoietic antigens have delivered selective radiation to marrow, spleen and lymph nodes in animal models and are being used in Phase I studies of marrow transplantation for acute leukemia. PMID- 1418733 TI - Monoclonal antibodies in the detection and therapy of micrometastatic epithelial cancers. AB - The initial promise of monoclonal antibodies as major therapeutic agents in human epithelial cancer has not been realized. Inaccessibility of cells in solid tumors due to factors such as the nature of the vascular endothelia and high pressure in the tumor are primarily responsible for the failure of antibody therapy. Although new strategies employing recombinant antibodies and immunoglobulins designed to actively engage the immune system may prove beneficial, micrometastatic tumor cells (at the stage of minimal residual disease) are likely to be the only suitable targets for antibody therapy. The diagnostic approaches to identify and characterize these cells and their use for prognosis and monitoring adjuvant immunotherapy is discussed. PMID- 1418734 TI - Transplantation. PMID- 1418735 TI - Reproduction. PMID- 1418736 TI - Cancer. PMID- 1418737 TI - Strong binding of single-stranded DNA by stem-loop oligonucleotides. AB - We report that oligodeoxynucleotides which form stem-loop hairpin structures and which have pyrimidine-rich loops can form strong complexes with complementary single-stranded DNA sequences. Stem-loop oligonucleotides were constructed with a 25-nt T-rich loop and with variable Watson-Crick stems. The complexes of these oligomers with the sequence dA8 were studied by thermal denaturation. Evidence is presented that the complexes are one-to-one, bimolecular complexes in which the pyrimidine loop bases comprise the outer strands in a pyr.pur.pyr triplex, in effect chelating the purine strand in the center of the loop. Melting temperatures for the loop complexes are shown to be up to 29 degrees C higher than Watson-Crick duplex of the same length. It is shown that the presence of a stem increases stability of the triplex relative to an analogous oligomer without a stem. The effect of stem length on the stability of such a complex is examined. Such hairpin oligomers represent a new approach to the sequence-specific binding of single-stranded RNA and DNA. In addition, the finding raises the possibility that such a complex may exist in natural RNA folded sequences. PMID- 1418738 TI - Structure of poly d(A).poly d(T). AB - On the basis of the x-ray data from polycrystalline and well oriented fibers of the sodium salt of poly d(A).poly d(T) (Arnott et al, Nucl. Acids Res. 11, 4141 4155 (1983), a revised B'-DNA model incorporating B-like adenine and thymine strands is shown to give a much better x-ray agreement (R = 0.25) than the previously assigned model consisting of mixed sugar conformations in the two strands. The narrowing of the minor and the widening of the major grooves are promiscuous features of B'-DNA, which are common to all poly d(purine).poly d(pyrimidine) duplexes with two hydrogen bonded base-pairs and are in marked contrast with classical B-DNA. Due to modest propeller (-15 degrees), the cross strand diagonal hydrogen bonds (0.37 nm) in this duplex are not as strong as those in A,T-rich oligonucleotide crystal structures. PMID- 1418739 TI - Ultraviolet resonance Raman marker bands of the right to left helix structure transitions in DNA and polynucleotide model compounds. AB - The right to left helix structural transition in purine-pyrimidine alternating copolymers has been extensively studied by vibrational spectroscopies, amongst many other experimental approaches. Here, the use of resonance Raman spectroscopy in the ultraviolet region (223-, 257- and 281 nm excitation wavelengths) to monitor such structural changes is reviewed in the light of new results obtained on poly(dA-dC).poly(dG-dT) on one hand, and the previous results obtained on poly(dG-dC)2, poly(dA-dT)2 and natural DNA (Chicken erythrocytes) on the other. It is now possible to define B----Z transition marker bands involving the proper bases, which show a similar behaviour on structural transition whatever the composition of alternating purine-pyrimidine sequences: the 1580- and 1487 cm-1 lines of the purines, the 1486- and 1294 cm-1 lines of the pyrimidines are good markers in the vibrational spectra recorded at various UV excitation wavelengths. PMID- 1418740 TI - Salt-induced conformational transition of poly(d2NH2A-dT) studied by ultraviolet resonance Raman spectroscopy. AB - The conformational changes of poly(d2NH2A-dT) in aqueous solution, induced by increasing the NaCl concentration from 0.1M to 4M, have been monitored by ultraviolet resonance Raman spectroscopy, in using the 222-, 257- and 281 nm excitation wavelengths. These changes have been interpreted in comparing the polymer spectra to those of the mononucleotide compounds on one hand, and to those of other alternating purine-pyrimidine polymers on the other hand, i.e. poly(dG-dC) and poly(dA-dT) which showed a B to Z transition in going from low- to high salt concentrations. The high salt poly(d2NH2A-dT) spectra do not show any Raman marker line of the Z conformation. The spectroscopic results indicate that most of the ribose puckering goes from C2'-endo/anti to C3'-endo/anti in increasing the salt concentration. In addition the base stacking interactions, to which the resonance Raman effect is very sensitive, are not drastically changed upon salt variations. Thus the high salt structure of poly(d2NH2A-dT) remains a right-handed helix, likely under a dominant A conformation. PMID- 1418741 TI - A molecular dynamics simulation of a polyamine-induced conformational change of DNA. A possible mechanism for the B to Z transition. AB - A 75ps molecular dynamics simulation has been performed on a fully solvated complex of spermine with the B DNA decamer (dGdC)5.(dGdC)5. The simulation indicates a possible mechanism by which polyamines might induce the formation of a left-handed helix, the B to Z transition. Spermine was initially located in the major groove, hydrogen bonded to the helix. During the simulation the ligand migrates deeper into the DNA, maintaining strong hydrogen bonding to the central guanine bases and destroying the Watson-Crick base pairing with their respective cytosines. Significant rotation of these and other cytosine bases was observed, in part due to interactions of the helix with the aminopropyl chains of spermine. An intermediate BII conformation might be of importance in this process. PMID- 1418742 TI - Groove width and depth of B-DNA structures depend on local variation in slide. AB - The groove widths of DNA helix, especially minor groove width, are generally believed to be important for recognition of DNA by various types of ligands. It has been postulated earlier that large negative propeller twist, in the AT rich regions compresses the minor groove of duplex DNA. A systematic study has now been carried out by generating models with different values of local doublet and intra-basepair parameters and calculating their minor groove widths. It is found that several local doublet parameters affect the minor groove width but it depends most strongly on the local step parameters roll and slide when each parameter is considered individually. However, a detailed analysis of the various local parameters within the B-DNA family of crystal structures indicates that propeller twist and slide are most strongly correlated with the observed values of minor groove width. The groove depth is also strongly correlated with slide. Thus the local base sequence dependent variations in slide can modify both the groove width and depth and consequently determine the ligand binding properties of DNA. PMID- 1418743 TI - Plasmon interpretation of 25 cm-1 mode in DNA. AB - An extension of the effective field approach for the normal mode dynamics of dissolved DNA polymers has been applied to study the vibrational modes of DNA hydration sheath-counterion system, to include the effect of site bound counterions on the system dynamics. An alternative interpretation has been suggested for a 25 cm-1 mode recently observed in DNA samples and interpreted earlier as an interhelical mode. Analysing the eigenvectors this mode is found to possess a large electric dipole moment with longitudinal collective oscillations of the system. These characteristics identify this mode as a collective plasmon mode. Possible physical reasons for the existence of this character have been presented. PMID- 1418744 TI - Lipid conformational nomenclature: a general method. AB - We propose a conformational nomenclature for amphiphilic lipid molecules that is general and compatible with the stereospecific numbering scheme, in contrast to earlier methods in which discrepancies with the sn-scheme lead to contradictory assignments of the absolute configuration of the system. The present method can be rationally extended to different classes of lipids, both natural and synthetic. It is simple and provides a convenient framework for conformational studies on widely varying classes of lipids. PMID- 1418745 TI - Diffusion-enhanced energy transfer investigation of histone H5 in chromatin with a fluorescently-labelled antibody fragment Fab'. AB - The location of chicken erythrocyte H5 histone relative to the axis the 30 nm chromatin fibre axis has been investigated by diffusion-enhanced energy transfer. In this investigation, a neutral lanthanide chelate as donor and a fluorescent probe specific to H5 as acceptor have been used. The acceptor probe consists of H5 antibody Fab' fragment, which has been labeled with 5-iodoacetamidofluorescein (5-IAF). Using H5 fragments we have shown by ELISA that the antibodies recognized the N- and C-terminal ends of this histone. A neutral chelate of terbium (TbHED3A) was chosen as a suitable donor for energy transfer with IAF-labelled Fab' (Fab'-IAF) bound to H5 in various chromatin structures. The ionic strength dependence of the energy transfer from TbHED3A to chromatin-bound Fab'-IAF was used to estimate the accessibility and the location of the Fab' in chromatin. The rate constants for energy transfer, obtained from the lifetimes of the TbHED3A excited state in presence and absence of acceptor, indicated a decrease in transfer efficiency upon increase of salt concentration from 5 to 80 mM NaCl. This can be correlated with the chromatin folding occurring in this ionic strength range and is consistent with the location of at least some of the N and C-termini of H5 within the condensed chromatin structure. PMID- 1418746 TI - Transcription regulation by steroid hormones: a computer simulation study. AB - Three-dimensional structures of complexes of 66 amino acid-DNA binding domains of human progesterone (hPR), estrogen (hER) and glucocorticoid (hGR) receptors (proteins), with ten base pair DNA duplexes: d(AGGTCATGCT).d(AGCATGACCT) and d(AGAACATGCT).d(AGCATGTTCT) were obtained using computer modeling and molecular mechanics techniques. Cartesian coordinates for the proteins were obtained from: 1) structural data of hER and hGR by NMR spectroscopy; 2) steric constraints imposed by tetrahedral coordination of the zinc ion to Cys residues, and 3) energy minimization in torsional and cartesian space. The proteins were made to interact with DNA (in B-form) in major groove through alpha-helical linker between the two zinc fingers. The geometry of the complexes was obtained by allowing them to slide, glide, penetrate in to and out of the groove, and to rotate about the helical axis. The complexes were energy minimized. Also maximized was the number of H-bonds between proteins and DNA. The complex structures were refined by molecular mechanics using AMBER 3.0. Structural parameters of DNA were analyzed in each complex and compared with those of native DNA optimized separately. The stereochemical differences of the complexes are discussed. PMID- 1418747 TI - Using lambda exonuclease inhibition assays to map carcinogen binding sites. AB - Previous restriction mapping studies (M.A. Mallamaci, D.P. Reed and S.A. Winkle, J. Biomolecular Structure and Dynamics, in press (1992)) have indicated that a small number of locations on the plasmid pBR322 may be high affinity binding sites for the carcinogen N-acetoxy-N-acetyl-2-aminofluorene (acetoxyAAF). PBR322 was reacted with acetoxyAAF to produce DNA with one, three or seven acetoxyAAF moieties per DNA molecule. Thus only the higher affinity binding sites are affected. Subsequent digestion with the restriction enzyme Hinf I produced fragments containing previously indicated locations of potential acetoxyAAF binding sites. Fragments thought not to contain binding sites were also examined as controls. The isolated fragments, singly 32P end-labeled, were digested with lambda exonuclease. The three fragments suspected of containing acetoxyAAF binding sites possess new lambda exonuclease inhibition sites when the fragments are obtained from acetoxyAAF reacted DNA. No such inhibition sites are found with the two fragments suggested previously not to contain acetoxyAAF binding sites. These carcinogen produced inhibition sites occur in sequences which are similar, suggesting that acetoxyAAF preferentially may target a small number of sequences. PMID- 1418748 TI - Restriction enzyme mapping of carcinogen binding regions on pBR322. AB - Previous equilibrium binding experiments (S.A. Winkle and T.R. Krugh, Nucleic Acids Res. 9, 3175-3186 (1981)) suggested that the carcinogen N-hydroxy-N-acetyl 2-aminofluorene might exhibit preferential binding to a small number of sites on phiX174 DNA. To examine whether the covalently binding analogue N-acetoxy-N acetyl-2-aminofluorene (acetoxyAAF) also possesses high affinity sites, the plasmid pBR322 was reacted with 3H labeled acetoxyAAF to give one to sixteen adducts per DNA molecule. Thus only higher affinity sites would be affected. The DNA was subsequently cleaved with either Alu I, Hae III, Hha I, Hinf I or Hpa II restriction endonuclease and the restriction fragments isolated by gel electrophoresis. Examination of the distribution of 3H acetoxyAAF among the fragments was not random but, rather, with each enzyme, the acetoxyAAF was found predominantly in a few fragments. The locations of the bands containing the acetoxyAAF for each enzyme overlap--suggesting that there are regions on pBR 322 which contain high affinity sites for acetoxyAAF binding. PMID- 1418749 TI - Conformation and dynamics of drug-DNA intercalation. AB - Molecular dynamics simulations have been undertaken for a B-form dodecanucleotide duplex in solution with and without an intercalated proflavine molecule between the central C.G base pairs. The introduction of this simple intercalator affects both the conformational features and dynamic properties of the oligonucleotide double helix. Changes are seen in the rms atomic fluctuations and anisotropy of phosphate, sugar and base atoms. The backbone conformation is slightly changed on average and more sugars adopt the C3' endo conformation in the simulation of the complex compared with the simulation of the oligonucleotide alone. Both major and minor grooves becomes wider on average with the addition of the intercalating drug. Flanking A.T base pairs on both sides of the intercalation site have undergone an increase in flexibility, with the base pairs, especially at the 5' side, having the N1...N3 hydrogen bonds being broken. PMID- 1418750 TI - The serotoninergic system of the brain of the lamprey, Lampetra fluviatilis: an evolutionary perspective. AB - The distribution of serotonin(5HT)-immunoreactive cell bodies, nerve fibers and terminals was investigated by light microscopy in the lamprey Lampetra fluviatilis. Twenty-three distinct groups of 5HT neuronal somata were identified from diencephalic to rhombencephalic levels in the brain. The diencephalon contained a subependymal population of immunoreactive cells in contact with the cerebrospinal fluid (CSF), which could be subdivided into five separate groups situated in the hypothalamus and ventral thalamus; five additional groups of immunoreactive diencephalic neurons, situated in the dorsal thalamus and thalamo pretectum, which were not in contact with the CSF, were also identified. In the midbrain, in addition to a few labelled neurons in the optic tectum, two structures containing immunoreactive cells were identified in the tegmentum mesencephali. None of these 5HT cells corresponded to the retinopetal neurons which are situated in the same region. A very large number of 5HT neurons were observed in the hindbrain which could be divided into seven groups in the isthmus rhombencephali and a further three in the rhombencephalon proper. Immunoreactive fibers and terminals were widely distributed throughout the neuraxis. In the telencephalon two 5HT fibers assemblies, lateral and medial, could be identified which terminated in both pallial and subpallial structures. The richest serotoninergic innervation in the telencephalon was found in the lateral portion of the primordium hippocampi and the medial part of the corpus striatum. In the diencephalon, the distribution of immunoreactive fibers and terminals was heterogeneous, being most pronounced in the lateral hypothalamic area and in the infundibulum. The densest arborization of fibers in the mesencephalon was found in the stratum fibrosum et cellulare externum of the optic tectum, a major site of retinal projection, and in the nucleus interpeduncularis mesencephali as well as in the oculomotor nuclei. The rhombencephalon is richly endowed with serotoninergic fibers and terminals, many labelled arborizations being found in the nuclei isthmi rhombencephali and around the nucleus motorius nervi trigemini. Comparative analysis of the serotoninergic systems of petromyzontiforms and gnathostomes indicates that the evolution of this system involves a progressive elimination of the rostral immunoreactive cells and an increasing complexity of the caudal population of serotoninergic neurons. PMID- 1418751 TI - Characteristics of labeling of the cerebellar Purkinje neuron by L7 antiserum. AB - Previously, it has been shown by light microscopy that antiserum to the L7 protein labels cerebellar Purkinje neurons. Herein we show by light and electron microscopic immunocytochemistry that all cerebellar Purkinje cells express L7 and that the gene product is distributed to all neuronal compartments, including the nucleus. Possible functional roles for L7, based on its subcellular localization, are discussed. L7 is proposed as an excellent marker molecule for future studies of normal and aberrant cerebellar development. PMID- 1418752 TI - The distribution of cholinergic muscarinic receptors in the dog frontal lobe. AB - The topographical distribution of cholinergic muscarinic receptor (MChR) sites was studied by means of quantitative receptor autoradiography using [3H]quinuclidinyl benzilate ([3H]QNB) in the frontal (prefrontal, premotor and motor) cortex of the dog. The mean binding value in the frontal cortex was 408 +/ 5.0 fmol/mg tissue and the only area that differed significantly from the mean was the primary motor cortex, where the binding value was significantly lower. In the dorsal part of the prefrontal and premotor cortical subregions studied, a tri laminar pattern of [3H]QNB labelling was observed, with a superficial dense band of label corresponding to cortical layers I, II and III. The deep high density band overlaid layer V and the upper part of the layer VI. In the ventral part of the prefrontal cortex this pattern gradually disappeared and in the most ventral part no laminar differences were seen. In contrast, in primary motor areas, the deep band of labelling corresponding to layer V was much less pronounced than in the frontal association cortex. Variations in the distribution of MChR sites seem to reflect to some extent the greater cytoarchitectonic differentiation of the dorsal zone and also the similarity between the ventral zone and the limbic cortex described by us previously. PMID- 1418753 TI - Autoradiographic distribution of [3H]nicotine binding in human cortex: relative abundance in subicular complex. AB - Distinct patterns of [3H]nicotine (3 nM) binding were apparent in various regions of adult human neo- and archicortex. Receptor binding was greatest in the subicular complex--particularly presubiculum--and entorhinal cortex, where it was prominent in the characteristic parvo- and magnocellular islands of these regions and in middle layers of entorhinal cortex. In somatosensory cortex (Brodmann areas 3, 1 and 2) and occipital (area 17) cortex binding was highest in the upper and lower layers, and relatively sparse in the sensory input, layer IV. In primary motor (area 4) and temporal (area 21) cortex, binding in the outer half of the cortical ribbon was denser than that in the inner half and a distinct band was apparent in temporal and cingulate (area 32) in the lower portion of layer III. In prefrontal association cortex the pattern of binding was less distinct although slightly higher in the lower architectonic layers. There was generally little binding in the hippocampus (areas CA1-4) and dentate gyrus with the exception of the stratum lacunosum moleculare in CA2-3 and, to a lesser extent, supra- and subgranule zones of the dentate. These patterns of reactivity, which are distinct from that of the major cortical cholinergic innervation, suggest that the nicotinic receptor, detected using nanomolar concentrations of [3H]nicotine, may primarily be associated with intracortical circuitry in the neocortex. The relatively high density in entorhinal and subicular regions may be related to the extensive phylogenetic development of these regions which has occurred in conjunction with the development of multimodal association circuitry in the human cortex. PMID- 1418754 TI - Adrenergic projections from the lower brainstem to the hypothalamic paraventricular nucleus, the lateral hypothalamic area and the central nucleus of the amygdala in rats. AB - Fine networks of phenylethanolamine N-methyltransferase (PNMT)-immunoreactive fibers are found in the hypothalamic paraventricular nucleus--mainly in the anterior, dorsal and dorso-medial parvicellular subdivisions, the lateral hypothalamus (dorsal, lateral and ventral to the fornix) and in the central amygdaloid nucleus. Coronal hemisections of the brainstem through the rostral level of the medulla oblongata show that most hypothalamic and amygdaloid PNMT fibers arise from the medullary adrenergic cell groups. Fourteen, but not 10 days after total hemisections, PNMT fibers disappeared almost completely from the hypothalamus and amygdala, ipsilateral to the knife cuts. A small decrease was also observed in the ventral, lateral hypothalamus on the contralateral side. Partial depletion of PNMT-immunoreactivity in the hypothalamus and the amygdala after medial or lateral brainstem hemisections indicates that ascending PNMT immunoreactive fibers pass through mainly the lateral portion of the medulla, but some fibers also in its medial portion. Midsagittal transection of the diencephalon slightly reduced PNMT immunostaining in the paraventricular nucleus and the lateral hypothalamus bilaterally. The results show that the ascending PNMT system essentially is ipsilateral, but probably with a small crossing-over component, both at the diencephalic and lower brainstem level. PMID- 1418755 TI - Immunohistochemical study of the catecholaminergic innervation of the spinal cord of the rat using specific antibodies against dopamine and noradrenaline. AB - We have assessed the relative contributions of dopaminergic and noradrenergic descending systems to the catecholaminergic innervation of the rat spinal cord. Fibres and terminals were labelled with their own neurotransmitter by using specific antibodies raised against dopamine (DA) and noradrenaline (NA) respectively. For this purpose, immunohistochemistry according to the peroxidase anti-peroxidase technique was performed in different experimental conditions. Two group of rats received intracisternal 6-hydroxy-dopamine (6-OHDA) injections either with or without benzatropine pretreatment. Animals of a third group were not pretreated at all. While 6-OHDA induced a complete disappearance of spinal NA like immunoreactivity (NA-LI), except for scarce residual fibres in the thoracic intermedio-lateral cell column, DA-like immunoreactivity (DA-LI) was unaffected by the lesion. This strongly suggests that the antisera used specifically labelled NA-containing and DA-containing fibres respectively. Spinal DA-LI and NA LI innervations differed markedly in their topographical distributions and in the morphology of the corresponding fibres. DA-LI innervation was restricted to laminae I, III and IV and to the intermediate zone, especially the autonomic areas. In the ventral horn, it was sparse and more visible after acidification of the fixation solution. NA-LI innervation was much more widely spread. In addition, the organization of NA-LI fibres suggests that the innervation of the whole dorsal horn comes from a group of fibres travelling, at least partially, in the superficial dorsal horn. PMID- 1418756 TI - Lung adenoma development and NK activity in mice treated with multiple carcinogens. AB - A wide-spectrum initiation model was investigated in mice. Sequential treatments with diethylnitrosamine, urethane and N-methylnitrosourea, with or without a promoter, phenobarbital, resulted in tumor formation in the lungs in 85-90% of animals, but did not produce any tumorous lesions in other organs. The lung tumors were adenomas and the mean number of adenomas was 2.2-2.6 per mouse. Phenobarbital combination had no additive effect on lung tumor incidence and multiplicity. Splenic NK cell activity showed inconsistent increment in the carcinogen plus phenobarbital-treated group during the experiment (P less than 0.05). PMID- 1418757 TI - Technetium-99m HM-PAO SPECT in patients with delayed neurologic sequelae after carbon monoxide poisoning. AB - We used single photon emission computed tomography (SPECT) with technetium-99m hexamethylpropylene amine oxime (99mTc-HM-PAO) in 14 studies on 6 patients with delayed neurologic sequelae from carbon monoxide (CO) poisoning to determine whether any changes in cerebral blood flow could be correlated with clinical or computed tomographic evidence of delayed deficits. Among the six initial CT brain scans, two showed low density of both basal ganglia and two showed decreased density of the cerebral white matter. There was no correlation between the clinical outcome and the findings of the follow-up CT brain scans. Of the two SPECTS with 99mTc-HM-PAO performed during acute anoxic insult, one showed focal hypoperfusion which appeared 20 days prior to the onset of delayed neurologic sequelae after CO poisoning. Seven SPECTs in the six patients performing the delayed phase showed diffuse patched patterns of hypoperfusion which improved on follow-up images. There was good correlation between the clinical outcome and the findings of the 99mTc-HM-PAO SPECT. In preliminary conclusion, 9Tc-HM-PAO brain SPECT can be used for predicting or evaluating the outcome of delayed neurologic sequelae after CO poisoning. Cerebral vascular changes may be the possible cause of hypoperfusion in patients with CO poisoning. PMID- 1418758 TI - Variations of the ventral rami of the brachial plexus. AB - We studied the variations in the ventral rami of 152 brachial plexuses in 77 Korean adults. Brachial plexus were composed mostly of the fifth, sixth, seventh and eighth cervical nerves and the first thoracic nerve (77.0%). In 21.7% of the cases examined, the fourth, fifth, sixth, seventh and eighth cervical and the first thoracic nerves contributed to the plexus. A plexus composed of the fourth, fifth, sixth, seventh and eighth cervical and the first and second thoracic nerves, and a plexus composed of the fifth, sixth, seventh eighth cervical nerves were also observed. The plexuses were classified into three groups according to cephalic limitation, and the plexus of group 2 in which the whole fifth cervical nerve enters the plexus, were observed the most frequent. The average diameter of the sixth and the seventh cervical ventral rami of the plexus was greatest and that of the fifth cervical was smallest. The largest nerve entering the plexus was the sixth or the seventh cervical nerve in about 79% of cases. The dorsal scapular nerve originated from the fifth cervical ventral ramus in 110 cases (75.8%). The long thoracic nerve was formed by joining of roots from the fifth, sixth, and seventh cervical nerves in 76.0% of cases. Also, a branch to the phrenic nerve, the suprascapular nerve, a nerve to the pectoralis major muscle and a nerve to the subscapular muscle arising from the ventral rami of the plexus were observed. PMID- 1418759 TI - Anatomical observation on draining patterns of saphenous tributaries in Korean adults. AB - This study was done to identify the normal and variants of saphenous tributaries in Korean adults. The pattern of confluence of saphenous tributaries, medial accessory saphenous, lateral accessory saphenous, superficial epigastric, superficial circumflex iliac and superficial external pudendal veins, was carefully examined in 249 lower limbs (right, 129; left, 120) of embalmed Korean cadavers (73 males & 56 females). The medial accessory saphenous vein drained into the great saphenous vein directly (in 82.3%) or by a common trunk (in 17.7%) with the superficial epigastric or superficial external pudendal vein. The lateral accessory saphenous vein entered the great saphenous (in 67.1%) or the femoral vein (in 32.9%) directly or, forming a common trunk with other saphenous tributaries. The superficial epigastric vein joined the great saphenous (in 77.1%) or the femoral vein (in 22.9%) directly or, by a common trunk with other saphenous tributaries. The superficial circumflex iliac vein reached the great saphenous (in 83.1%) or the femoral vein (in 16.9%) directly or, by a common trunk with other saphenous tributaries. The superficial external pudendal vein opened into the great saphenous (in 95.2%) or the femoral vein (in 4.8%) directly or by a common trunk with other saphenous tributaries. In Koreans, the incidence of the normal pattern of saphenous tributaries was 23.7% and in 76.3% any one of variant saphenous tributaries entered the femoral or the great saphenous vein by a common trunk with other saphenous tributaries. PMID- 1418760 TI - Predictable ultrasonographic findings of early abortion. AB - Early fetal growth delay and early oligohydramnios have been suspected as signs of embryonal jeopardy. However, little information is available for the prediction of early abortion. Sonographic examination of 111 early pregnancies between the sixth and ninth gestational week with regular, 28 day menstrual cycles was performed to investigate predictable sonographic findings of early abortion. Sonographic measurements of the gestational sac (G-SAC), crown-rump length (CRL) and fetal heart rate (FHR) were performed using a linear array real time transducer with Doppler. All measurements of 17 early abortions were compared to those of 94 normal pregnancies to investigate the objective rules for the screening of early abortion. Most of the early aborted pregnancies were classified correctly by discriminant analysis with G-SAC and CRL (G-SAC = 0.5222 CRL + 14.6673 = 0.5 CRL + 15, sensitivity 76.5% specificity 96.8%). With the addition of FHR, 94.1% of early abortions could be predicted. In conclusion, sonographic findings of early intrauterine growth retardation, early oligohydromnios and bradycardia can be predictable signs for the poor prognosis of early pregnancies. PMID- 1418761 TI - The effect of hyperglycemia on lipid peroxidation in the global cerebral ischemia of the rat. AB - To investigate the influence of hyperglycemia on ischemic brain damage, we measured brain ATP, lactate and malondialdehyde (MDA) levels in global cerebral ischemic models of Wistar rats. We induced global cerebral ischemia by the 4 vessel occlusion method. After 30 or 60 min of occlusion, and after 30 min of reperfusion, we measured brain ATP, lactate and MDA levels. During the ischemic period, brain ATP levels decreased to 30-70% of sham groups both in normoglycemic and hyperglycemic groups. But during the reperfusion period, the recovery rate of ATP levels was significantly lower in the hyperglycemic than in the normoglycemic groups (p less than 0.05). After 60 min of global ischemia, brain lactate increased much more in the hyperglycemic than in the normoglycemic group, and, during reperfusion, was washed out slowly in the hyperglycemic group. The MDA level, a parameter of lipid peroxidation, increased more in the hyperglycemic group than in the normoglycemic group during reperfusion periods (p less than 0.05). We conclude that hyperglycemia increases lactate accumulation, delays the recovery of energy metabolism, and enhances the lipid peroxidation in the transient global ischemia of rat brain. These findings may suggest the harmfulness of hyperglycemia in clinical cerebral ischemia. PMID- 1418762 TI - Small-sized acute subdural hematoma: operate or not. AB - A retrospective study of 90 cases of small-sized (less than 3 mm on the printed CT film) acute (within 24 hours) subdural hematoma (SASDH) is presented. From March 1985 to December 1986, the SASDH were immediately operated on (operation rate: 86.0%). From January 1988 to December 1989, we attempted to treat them conservatively (operation rate: 49.1%). The patient population for this study consisted of 38 surgically-treated patients in the first period (Group I), 26 surgically-treated patients in the second period (Group IIs), and 26 conservatively-treated patients in the second period (Group IIc). We compared the clinical features, radiologic findings, and outcome of these 3 groups. The clinical features of Group I, including age, sex, Glasgow Coma Scale (GCS) score on admission, pupillary status on arrival, and interval from injury to the CT, did not differ significantly from those of Group II (P greater than 0.01). The only difference was the timing of the operation. In Group I, 20 patients (52.6%) received an operation within 4 hours, while in Group IIs, only 7 patients (26.9%) underwent surgery within 4 hours (P less than 0.05). The radiologic findings of Group I, including the thickness and volume of the hematoma, the degree of midline shift, and the frequency of skull fracture, also did not differ from those of Group II (P greater than 0.1). However, the outcome of Group II strikingly differed from that of Group I. The mortality rate was 76.3% in Group I, while it was 44.2% in Group II (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418763 TI - Ossifying fibroma of the sella turcica. AB - Ossifying fibroma of the sellar turcica is extremely rare. There are only sporadic case reports in the literature. One such case simulating pituitary adenoma is presented in an 18-year-old girl. PMID- 1418764 TI - Arterial oxygen desaturation rate following obstructive apnea in parturients. AB - This study was attempted to observe the rate of oxygen desaturation after full oxygenation in six parturients scheduled for Cesarean sections and six patients scheduled for transabdominal hysterectomies. We calculated the mean rate of fall of arterial saturation (slope of desaturation: less than SaO2 (t2)-SaO2(t1) greater than/t2-t1) and changes in arterial blood gases were observed. All subjects were denitrogenated then a single isolated apnea was carried out. The mean time to obtain 90% saturation was longer in the nonpregnant group (7.5 min vs 3.6 min in parturients). The mean slope of desaturation was steeper in the parturients (-3.34) than the nonpregnant group (-1.52). As far as the oxygen reserve is concerned, the parturients had a lesser margin of safety than the nonpregnant women. It was concluded that the lower the thoracic gas volume (parturients), the lower the alveolar O2 stores and, the more rapidly these stores are depleted. PMID- 1418765 TI - Portal and superior mesenteric venous gas with retroperitoneal abscess--CT diagnosis (case report). AB - We present a case of portal and superior mesenteric venous gas in a 31-year-old diabetic woman with a left-sided retroperitoneal abscess. Five years prior to admission, patient was diagnosed with diabetes mellitus and developed emphysematous pyelonephritis, requiring nephrectomy on the left side. A CT examination showed air distributed throughout the portal venous system and superior mesenteric vein. PMID- 1418766 TI - Thrombotic thrombocytopenic purpura-like syndrome associated with systemic lupus erythematosus--combined treatment with plasmapheresis and fresh frozen plasma infusion. AB - We report on a patient with systemic lupus erythematosus, who, during the course of the illness, developed thrombotic thrombocytopenic purpura. In this case, the coexistence of these two conditions was confirmed by laboratory and pathologic findings. The infusion of fresh frozen plasma with plasmapheresis reversed the course of thrombotic thrombocytopenic purpura. PMID- 1418767 TI - Glucose-6-phosphate dehydrogenase deficiency--report of 4 cases. AB - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary enzyme disorder and more than 200 million people have a deficiency in this enzyme. It is a globally important cause of neonatal jaundice and causes life threatening hemolytic crisis in childhood. At later ages, certain drugs such as antimalarials, and fava beans cause hemolysis among G6PD deficiency patients. The frequency and severity is influenced by genetic and cultural factors. It is common in Mediterranean, African, and some East Asian populations but rare in Korea. Four cases of G6PD deficiency which were first noticed in Korea are investigated with their clinical features. PMID- 1418768 TI - Localized form of colitis cystica profunda--a case of occurrence in the descending colon. AB - An unusual localization of localized colitis cystica profunda in a 31-year-old man is described. The patient presented as anal bleeding and a protruding mass at the descending colon; the mass was polypoid and was made up of papillary epithelial hyperplasia with downward herniation of glands into the submucosa. Only one similar case involving a descending colon has been reported in the world literature. PMID- 1418769 TI - POEMS syndrome--a case report. AB - POEMS syndrome is a multisystem disorder associated with polyneuropathy, organomegaly, endocrinopathy, a monoclonal protein (M-protein), and skin changes. The authors describe a patient with POEMS syndrome who had osteosclerotic myeloma confirmed by open bone biopsy. Magnetic resonance imaging (MRI) showed discrete lesions of low signal intensity in both T1 and T2-weighted images. This patient is now being successfully treated with melphalan and prednisone with much improvement in skin thickening and sensory change in the lower extremities. PMID- 1418770 TI - Nerve sheath myxoma (neurothekeoma)--a case report. AB - A case of nerve sheath myxoma also called as neurothekeoma in a 33-year-old woman is described. The lesion appeared as a painful, elevated nodule on the scalp for several months, without an appreciable increase in size. Microscopically, it showed typical histologic characteristics of nerve sheath myxoma, and tumor cells revealed strong, positive reaction for S-100 protein and negativity for epithelial membrane antigen (EMA) on immunohistochemical staining. These immunohistochemical findings of this case support the view that the origin cells of this tumor may be schwann cells rather than perineurial cells. The histogenesis and differential diagnosis of this tumor are discussed. PMID- 1418771 TI - Carbon monoxide exposure of subjects with documented cardiac arrhythmias. AB - The impact of low-level carbon monoxide exposure on ventricular arrhythmia frequency in patients with ischemic heart disease has not been thoroughly studied. The issue is of concern because of the potential proarrhythmic effect of carbon monoxide in patients with ischemic heart disease. We studied 30 subjects with well-documented coronary artery disease who had an average of at least 30 ventricular ectopic beats per hour over a 20-hour monitoring interval. By using appropriate inclusion and exclusion criteria, subjects were selected and enrolled in a randomized double-blind study to determine the effects of carbon monoxide exposure on ventricular arrhythmia frequency at rest, during exercise, and during ambulatory activities. The carbon monoxide exposure was designed to result in 3% or 5% carboxyhemoglobin levels, as measured by gas chromatography. The carbon monoxide exposure protocol produced target levels in 60 minutes, and the levels were maintained for an additional 90 minutes to provide adequate time to assess the impact of carbon monoxide on the frequency of ventricular ectopic beats. The data on total and repetitive ventricular arrhythmias were analyzed for seven specific time intervals: (1) two hours before carbon monoxide exposure; (2) during the two-hour carbon monoxide or air exposure; (3) during a two-hour rest period; (4) during an exercise period; (5) during an exercise recovery period; (6) six hours after carbon monoxide or air exposure; and (7) approximately 10 hours after exposure, or the remaining recording interval on the Holter monitor. There was no increase in ventricular arrhythmia frequency after carbon monoxide exposure, regardless of the level of carboxyhemoglobin or the type of activity. During steady-state conditions at rest, the number of ventricular ectopic beats per hour was 115 +/- 153 (SD) for room air exposure (0.7% carboxyhemoglobin), 121 +/- 171 for the lower carbon monoxide exposure (3.2% carboxyhemoglobin), and 94 +/- 129 for the higher carbon monoxide exposure (5.1% carboxyhemoglobin). The frequency of complex ventricular ectopy was not altered at the levels of carbon monoxide studied. Secondary analysis of the impact of carbon monoxide on ventricular ectopic beat frequency stratified by baseline ejection fraction, baseline ventricular ectopic beat frequency, and exercise-induced ST-segment changes did not indicate an effect of carbon monoxide on ventricular arrhythmias. In conclusion, low levels of carbon monoxide exposure resulting in blood levels of 3.2% and 5.1% carboxyhemoglobin, as measured by gas chromatography, do not have a proarrhythmic effect on patients with coronary artery disease and frequent ventricular ectopy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1418773 TI - Nonlamellar phases formed by membrane lipids. AB - A brief review of membrane lipids forming cubic and reversed hexagonal phases is presented. An emphasis is made on anionic lipids and particular microbial lipids. PMID- 1418772 TI - A technique to estimate the apparent surface pressure of emulsion particles using apolipoproteins as probes. AB - The apparent pressures in the surface monolayer of emulsion particles can be estimated by comparing the absorption of an apolipoprotein to planar lipid monolayers and to emulsions. Lipids are spread at an air-water interface in a Pockels/Langmuir surface balance and the adsorption of [14C]-labeled apolipoproteins placed in the subphase is studied as a function of surface pressure using the surface radioactivity method. An apoprotein surface concentration/initial lipid surface pressure curve (gamma/pi i) is constructed. The maximum apolipoprotein surface concentration gamma e of emulsions is derived from standard emulsion/apolipoprotein binding isotherms. The apparent emulsion surface pressure is then estimated by comparing gamma e to the gamma/pi i curve. Apolipoprotein A-I has been used as an example of a probe to estimate the effective surface pressure in approximately 1000 A diameter egg yolk phosphatidylcholine/cholesterol/triolein emulsion particles. When the cholesterol content of emulsions is low, the surface pressure of the emulsion is about 17 dyne cm-1. At high cholesterol concentrations (0.49 cholesterol/phospholipid mole ratio) the surface pressure is increased to 25 dyne cm-1. The addition of the maximum amounts of apoA-I to these particles raises the effective surface pressure of the emulsion to about 30 dyne cm-1 and stabilizes the particles. PMID- 1418774 TI - The HIV-1 nef gene product is associated with phosphorylation of a 46 kD cellular protein. AB - OBJECTIVE: To study the biochemical properties of the HIV-1 nef gene product. DESIGN: Earlier reports suggested that Nef protein is phosphorylated and has kinase activity. These properties were examined using an in vitro translated product. METHODS: A DNA fragment encoding Nef of HIV-1SF2 was transcribed in vitro under the control of T7 promoter. The generated nef messenger RNA (mRNA) was translated using a rabbit reticulocyte lysate system. Immunoprecipitation was performed with a specific monoclonal antibody to Nef. Kinase activity of the translated product was evaluated using [gamma-32P]GTP and ATP. RESULTS: Translated nef mRNA was found to encode a major protein of 27 kD with two other products, of 25 and 29 kD. Using Nef immune complexes for the kinase reaction, a protein of 46 kD that reacted with the anti-Nef monoclonal antibody was found to be strongly phosphorylated in the presence of Nef. This Nef-associated kinase activity on a p46 cellular substrate was dependent on ATP. CONCLUSIONS: The in vitro-translated nef gene product was found to be associated with phosphorylation of a p46 cellular protein present in rabbit reticulocyte lysate. The Nef protein has been linked to suppression of the replication of certain HIV strains. Identification of cellular targets of Nef activity could help to elucidate the mechanisms for this antiviral effect. PMID- 1418776 TI - Development of HIV-1 group-specific neutralizing antibodies after seroconversion. AB - OBJECTIVE: To study the induction of group-specific (gs) neutralizing antibodies to HIV-1 after seroconversion. DESIGN AND METHODS: Serum samples taken sequentially from seven Dutch homosexual men and four British haemophiliacs (anonymous sample, therefore sex not known) before and after seroconversion were tested for neutralizing antibodies effective against five diverse HIV-1 strains. Strains of HIV-1 tested included isolates from the United States, Europe and Africa. RESULTS: The gs neutralizing antibody response varied between individuals. Only five of the 11 individuals studied produced detectable neutralizing antibodies to laboratory-adapted HIV-1 strains (for example, IIIB) within 32 weeks of seroconversion. Most individuals initially produced antibodies effective against US/European isolates; the response then generally broadened to include the more diverse strains, i.e., African. CONCLUSIONS: These results suggest that the gs neutralizing target for HIV-1 is poorly immunogenic in vivo and is probably not highly conserved among diverse HIV-1 strains. PMID- 1418775 TI - Expression of activation antigens, HLA-DR and CD38, on CD8 lymphocytes during HIV 1 infection. AB - OBJECTIVE: To study the expression of the activation markers human leukocyte antigen (HLA)-DR and CD38 antigen on CD8+ T-lymphocytes in HIV-infected subjects and HIV-negative controls. DESIGN: Two- and three-colour flow-cytometric analysis. METHODS: Fresh peripheral venous blood was obtained from 16 HIV infected subjects, representing four different stages of HIV disease, and from six HIV-negative controls. Three-colour lymphocyte immunophenotyping was performed using peridinyl chlorophyll-A protein (PerCP)-conjugated anti-CD8 monoclonal antibody (MAb) in combination with anti-HLA-DR (phycoerythrin) and anti-CD38 (fluorescein isothiocyanate) MAb. RESULTS: The relative percentage of the lymphocyte populations thus defined differed between HIV-negative and HIV positive subjects and between HIV-infected subjects at different clinical stages of disease. Simultaneous expression of HLA-DR and CD38 within the CD8 T lymphocyte compartment increased from 8% in controls to 49% in asymptomatic HIV infected subjects (P less than 0.005). Symptomatic patients differed from asymptomatic seropositives by a further increase in the HLA-DR+ CD38+ CD8 subset. In AIDS patients, the HLA-DR+ CD38- CD8 subset decreased (P less than 0.05) and the HLA-DR- CD38+ CD8 subset increased (P less than 0.05), compared with the other HIV disease stage patients. CONCLUSION: There is a stage-associated pattern of HLA-DR and CD38 expression on CD8 T-lymphocytes during HIV infection; specific phenotypic patterns may have functional correlates in the host response to the virus. PMID- 1418777 TI - Glutathione depletion in HIV-infected patients: role of cysteine deficiency and effect of oral N-acetylcysteine. AB - OBJECTIVE: To determine whether a single oral dose of N-acetylcysteine corrects the deficiency of cysteine and glutathione in plasma and mononuclear cells of HIV infected patients. DESIGN: Pharmacokinetic and pharmacodynamic study. METHODS: Cysteine and glutathione were measured in plasma and peripheral blood mononuclear cells of patients at different stages of HIV infection before and after a single oral dose of N-acetylcysteine. RESULTS: At baseline, the plasma concentrations of glutathione and cysteine were significantly lower in HIV-infected patients than in healthy controls. The intracellular concentration of glutathione correlated with the absolute CD4 lymphocyte counts: the concentration of glutathione in mononuclear cells was significantly lower in patients with more advanced immunodeficiency. A single oral dose of N-acetylcysteine increased the concentration of cysteine in plasma and mononuclear cells of HIV-infected patients. Four hours after N-acetylcysteine administration, intracellular glutathione concentrations in the patients were moderately higher than at baseline and at 2 h. CONCLUSIONS: Oral N-acetylcysteine transiently increases the concentrations of cysteine and glutathione in mononuclear cells of patients with HIV infection. A sustained increase in intracellular cysteine may be necessary to normalize intracellular glutathione. This may be accomplished by repeat administration of N-acetylcysteine. PMID- 1418778 TI - The effect of treatment with zidovudine with or without acyclovir on HIV p24 antigenaemia in patients with AIDS or AIDS-related complex. AB - OBJECTIVE: To evaluate changes in serum HIV p24-antigen levels in a subset of patients who participated in a European/Australian double-blind, placebo controlled trial evaluating the efficacy of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) in patients with AIDS, AIDS related complex (ARC) or Kaposi's sarcoma (KS). DESIGN: Double-blind, placebo controlled randomized clinical trial of less than or equal to 6 months' therapy. SETTING: Samples were obtained from patients attending teaching hospital outpatient clinics in seven European countries and Australia. SUBJECTS: One hundred and ninety-seven HIV-infected patients (60 with AIDS and 137 with ARC or KS). MAIN OUTCOME MEASURES: Serum HIV p24-antigen levels measured using the Abbott HIV solid-phase enzyme immunoassay. RESULTS: Of 76 ARC/KS patients who were initially HIV p24-antigen-positive, one out of 25 randomized to placebo, eight out of 23 to zidovudine and 11 out of 28 to the zidovudine/acyclovir combination became antigen-negative. The proportion of patients who became antigen-negative was significantly higher in both the zidovudine group (P = 0.016) and the zidovudine/acyclovir group (P = 0.004), compared with the placebo group. There were no statistical differences between the zidovudine and the zidovudine/acyclovir groups. During the trial p24-antigen levels in the zidovudine-treated patients reached their minimum after 4-8 weeks of therapy, and tended to increase gradually thereafter. Disease progression occurred irrespective of whether p24-antigen levels declined during therapy. No association between p24-antigen responses to therapy and baseline disease stage, Karnofsky score or baseline CD4 cell count was detectable. CONCLUSION: Acyclovir does not potentiate the effect of zidovudine on p24-antigen levels. Change in antigen level in response to antiviral therapy needs further investigation before it is used as a surrogate marker for clinical efficacy of antiviral therapy. PMID- 1418779 TI - Pharmacokinetics of zidovudine in end-stage renal disease: influence of haemodialysis. AB - OBJECTIVE: To study the pharmacokinetics of zidovudine (ZDV) and its glucoronide metabolite (G-ZDV) in a patient with end-stage renal disease in haemodialysis. DESIGN: Pharmacokinetics study performed during and between haemodialysis sessions. METHODS: The patient was treated with oral ZDV (100 mg every 8 h). Concentrations of ZDV and G-ZDV were measured by radioimmunoassay. A monocompartmental model was used to calculate pharmacokinetic parameters. RESULTS: The peak plasma concentrations of ZDV and G-ZDV after drug administration between haemodialysis sessions were 0.57 and 10.01 micrograms/ml, respectively. The half-lives of ZDV and G-ZDV rose to 3.2 and 14.2 h, respectively. The total body clearance for ZDV in the period between haemodialysis sessions (0.44 l/kg/h) was 66% lower than normal values. The ZDV half-life was normalized by haemodialysis, the total body clearance of ZDV increased (1.12 l/kg/h) and the G-ZDV half-life shortened (5.9-7.9 h). Neither G ZDV accumulation nor derived ZDV toxicity occurred. CONCLUSIONS: Our data suggest that ZDV is safe and an efficient drug when administered at a dosage of 100 mg three times daily in patients with end-stage renal disease in haemodialysis sessions, and that ZDV and G-ZDV are cleared by haemodialysis. PMID- 1418780 TI - Pancreatitis and pancreatic dysfunction in patients taking dideoxyinosine. AB - OBJECTIVE: To describe the incidence, clinical characteristics and dose relationship of dideoxyinosine (ddI)-associated pancreatitis. DESIGN: Patients enrolled in a Phase I dose escalation trial of ddI [AIDS Clinical Trials Group (ACTG) 064] were evaluated for signs and symptoms of pancreatic dysfunction. SETTING: Two ACTG sites. PATIENTS: Forty-four patients with AIDS or AIDS-related complex (ARC) and a CD4 cell count less than or equal to 400 x 10(6)/l. MAIN OUTCOME MEASURES: Seven patients developed pancreatitis that lasted from 1 to 7 weeks and varied in severity from mild to life-threatening. Seven other patients had evidence of hyperamylasemia or hypertriglyceridemia. Six patients who developed pancreatitis were able to tolerate rechallenge with lower doses of ddI. RESULTS: Development of pancreatitis correlated with cumulative dose of ddI but not with stage of disease or concomitant medications. Cumulative dose was not significantly associated with development of hyperamylasemia or hypertriglyceridemia in patients without clinical pancreatitis. CONCLUSIONS: The development of pancreatitis in AIDS or ARC patients receiving ddI varies in severity and time course and is associated with cumulative dose. Patients who develop pancreatitis may be able to tolerate therapy with a lower dose after resolution of their symptoms. Patients receiving ddI require careful monitoring for the development of this complication. PMID- 1418781 TI - Progressive multifocal leukoencephalopathy in HIV-1-infected children. AB - OBJECTIVE: To describe the clinical and pathologic features of two HIV-1-infected children with progressive multifocal leukoencephalopathy (PML). DESIGN: Case report. SETTING: University-affiliated, public-health trust hospital. METHODS: Two HIV-1-infected children with PML are described. A 13-year-old girl, presumed to be congenitally infected with HIV-1, presented with dysarthria and paresthesias of the tongue and chin that evolved rapidly to dementia, muteness and severe spastic quadriparesis. The other patient, a 10-year-old boy who developed HIV-1 infection from a blood transfusion at the age of 3 years, presented with a facial palsy with subsequent development of right hemiparesis and aphasia. RESULTS: Brain biopsy in the first child and autopsy in the second confirmed the diagnosis of PML. In both patients, the CD4 T-lymphocyte count was less than 100 x 10(6)l at the time of neurological presentation. CONCLUSION: Despite seroepidemiological studies suggesting that the majority of individuals are infected with JC virus during childhood, PML is rare in children with impaired cell-mediated immunity. Our patients illustrate that PML is among the neurological complications of HIV-1 infection in children. PMID- 1418782 TI - The spectrum of HIV-1-related disease among outpatients in New York City. AB - OBJECTIVES: To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. DESIGN AND METHODS: The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. RESULTS: Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. CONCLUSIONS: These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations. PMID- 1418783 TI - Maintenance of behavioral change in a cohort of homosexually active men. AB - OBJECTIVES: To assess associations of perceptions of sexual behavior change with actual risk behaviors and psychosocial variables, and to determine whether perceptions of behavior change predict subsequent behavior. DESIGN: Cohort study of homosexually active men. SETTING: Community health center in Boston, Massachusetts, USA. PATIENTS, PARTICIPANTS: Two hundred and sixty-two cohort members who participated in follow-up in 1989 and who had at least one subsequent visit. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Composite risk behavior variable, based on unprotected anogenital contact and number of partners. RESULTS: Of the 96% who had effected behavior change, 47% perceived that they were able to maintain those changes consistently and 58% wanted to make more changes. Perceptions of consistent maintenance were associated with lower risk behavior, lower perceived riskiness of behaviors and susceptibility to AIDS, and fewer barriers to behavior change. Desire for more change was associated with increased behavioral effort, fewer barriers to condom use, and greater perceived riskiness of current behavior. Among those with lower risk behaviors, perceived inconsistent maintenance predicted relapse to more risky behavior at the following visit. CONCLUSIONS: Perceived maintenance of behavior change is potentially useful in identifying individuals at risk of relapse from safer sex. PMID- 1418784 TI - HIV prevalence, attitudes and behaviour in clients of a confidential HIV testing and counselling centre in Uganda. AB - OBJECTIVE: To describe clients, operation and impact of an African public HIV testing and counselling centre. DESIGN AND SETTING: Analysis of samples from clients attending the AIDS Information Centre (AIC) in Kampala, Uganda in early 1991. SUBJECTS: HIV-1-positive and HIV-negative consecutive clients (250 of each), 86 consecutive couples, and 200 consecutive clients who were HIV-negative in 1990 and were attending for their repeat test. MAIN OUTCOME MEASURES: HIV seroprevalence rates, attitudes, behaviour and behaviour change. RESULTS: HIV-1 prevalence was 28% overall, 24% in men and 35% in women. Reasons for taking the HIV test were a planned marriage or a new relationship (27%; 84% in couples), to plan for the future (35%), distrust of sexual partner (14%) and illness or disease/death (not HIV-specific) of partner (20%). The majority of the reported intentions in response to a positive or a negative HIV test result were positive, demonstrating the ability to cope with this information. Of repeat clients, two (1%) had become HIV-1-positive. The majority of repeat clients reported one sexual partner only (67%) or sexual abstinence (25%). Compared with pre-test information from AIC clients attending for the first time, repeat clients reported casual sexual contacts less often (6 versus 25%) and, of those, the majority used condoms. CONCLUSIONS: Our study demonstrates the demand for and the feasibility of confidential HIV testing and counseling services in Uganda, and illustrates the value of these services in achieving behaviour changes. Such services should be considered an additional approach for the reduction of HIV transmission in Africa, especially in areas with high HIV seroprevalence rates. PMID- 1418786 TI - AIDS-related secondary infections in patients with unknown HIV status. PMID- 1418785 TI - Safer sex maintenance among gay men: are we making any progress? PMID- 1418787 TI - A case for the revision of the WHO clinical definition for African AIDS. PMID- 1418788 TI - HIV infection in Cameroon: 30 months' surveillance in Yaounde. PMID- 1418789 TI - Characteristics of newborns and HIV-1 infection in Rwanda. PMID- 1418790 TI - HIV seroprevalence surveys in Uruguay. PMID- 1418791 TI - Specific antitoxoplasmic immunoglobulin G detected by western blot in AIDS patients: relationship to visceral localization. PMID- 1418792 TI - Role of proteases as cofactors for antibody-dependent enhancement of HIV. PMID- 1418793 TI - Antigenicity of the HIV-2 V3 loop. PMID- 1418794 TI - Intramedullary tuberculoma in a patient with HIV infection. PMID- 1418795 TI - Pneumopathy and kidney abscess due to Nocardia farcinica in an HIV-infected patient. PMID- 1418796 TI - Honesty, the best policy. PMID- 1418797 TI - Being cruel to be kind. PMID- 1418798 TI - Scottish affairs. PMID- 1418799 TI - Principles of stroke rehabilitation. Members from a multidisciplinary team working with stroke patients in the North West offer advice on successful strategies for rehabilitation. PMID- 1418800 TI - Evolution, not revolution. Primary nursing is the key to introducing successful discharge planning for elderly patients, argue Ann Hare and Penny Hillier. PMID- 1418801 TI - Moving together. Anne Herrick Nicodemus explains the ways in which elderly people can benefit from exercise and creative movement. PMID- 1418803 TI - World depression. PMID- 1418802 TI - Losing out in old age. PMID- 1418804 TI - Olympic shadows. PMID- 1418805 TI - ACE on ageing. PMID- 1418806 TI - As I was saying.... PMID- 1418808 TI - Now for the good news. PMID- 1418807 TI - Lifting and moving. PMID- 1418809 TI - Practice makes perfect. PMID- 1418810 TI - The collapse of caring. PMID- 1418811 TI - The structure of hexaaquaaluminium(III) bromate trihydrate, [Al(H2O)6](BrO3)3.3H2O. AB - Hexaaquaaluminium(III) bromate trihydrate, [Al(H2O)6](BrO3)3.3H2O, M(r) = 572.84, triclinic, P1, a = 9.536 (2), b = 11.095 (4), c = 9.291 (2) A, alpha = 106.58 (2), beta = 100.42 (2), gamma = 113.01 (2) degrees, V = 818.1 (4) A3, Z = 2, Dx = 2.33 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 74.58 cm-1, F(000) = 560, T = 296 K, R = 0.050 for 3777 unique reflections having I greater than sigma 1. The single type of Al ion is coordinated by six inequivalent water O atoms which form a slightly distorted octahedron. The average Al--O distance within the octahedron is 1.872 (11) A. Each of the three inequivalent bromate groups has three inequivalent O atoms. The average Br--O distances and O--Br--O angles for these ions are: 1.652 (25) A and 104.1 (17) degrees for Br(1)O3; 1.650 (9) A and 104.4 (18) degrees for Br(2)O3; 1.643 (9) A and 103.6 (14) degrees for Br(3)O3. The aluminium-oxygen complex conformed to rigid-body behavior but the bromate groups did not. Corrected for rigid-body motion, the average Al--O distance becomes 1.880 (10) A. Least-squares refinement of the positional parameters of the 18 inequivalent H atoms permitted a detailed analysis of the hydrogen bonding. PMID- 1418812 TI - The absolute configuration of an intermediate in the asymmetric synthesis of unusual amino acids. AB - (4R)-3-[(2'R,3'R)-2'-Bromo-3'-(phenylbutanoyl)]-4-(phenylmethyl)-2 - oxazolidinone, C20H20Br-NO3, M(r) = 402.30, monoclinic, P2(1), a = 11.542 (2), b = 7.625 (1), c = 11.667 (1) A, beta = 113.97 (1) degrees, V = 938.2 (2) A3, Z = 2, Dx = 1.42 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 21.8 cm-1, F(000) = 412, T = 296 +/- 1 K, final R = 0.028 for 2369 observed reflections. Since a D chiral auxiliary was used the configuration at the alpha-carbon was R as expected. The two carbonyls are aligned in opposite directions to each other to overcome van der Waals repulsions. PMID- 1418813 TI - Structure of difluorotriphenylphosphorane. AB - C18H15F2P, M(r) = 300.29, orthorhombic, Pbcn, a = 6.105 (2), b = 16.634 (3), c = 14.356 (3) A, V = 1458 (1) A3, Z = 4, Dx = 1.368 Mg m-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.194 mm-1, F(000) = 624, T = 294 K, R = 0.045 for 729 observed independent reflections. Difluorotriphenylphosphorane [(C6H5)3PF2] displays a trigonal bipyramidal geometry about the P atom, with the two F atoms occupying axial positions. The three phenyl groups in the equatorial positions are not 'geared' in a regular propeller arrangement; one of the three rings is twisted in the opposite direction to that of the other two. PMID- 1418814 TI - Structure of L-phenylalanine L-phenylalaninium formate. AB - C9H11NO2.C9H12NO2+.CHO2-, M(r) = 376.41, monoclinic, P2(1), a = 11.507 (6), b = 5.638 (3), c = 14.610 (5) A, beta = 100.65 (4) degrees, V = 932 (1) A3, Z = 2, Dx = 1.342 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 0.94 cm-1, F(000) = 400, T = 295 K, final R = 0.047 for 2693 observed reflections. The phenylalanine zwitterion and the phenylalanine cation form a Speakman-salt-type hydrogen bond [O ... O = 2.496 (3) A]. Aromatic side chains constitute a thick hydrophobic layer with edge-to-face interactions between the phenyl rings. PMID- 1418815 TI - Structure of tetralithium 1,4,5,8-naphthalenetetracarboxylate dodecahydrate. AB - 4Li+.C14H4O8(4-).12H2O, M(r) = 544.18, triclinic, P1, a = 9.608 (2), b = 10.034 (2), c = 7.033 (1) A, alpha = 94.29 (1), beta = 96.95 (1), gamma = 64.52 (1) degree, V = 607.4 (2) A3, Z = 1, D chi = 1.49 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 1.29 cm-1, T = 295 K, F(000) = 284, R = 0.039 for 2781 unique reflections having I greater than sigma I. The two inequivalent carboxyl groups adopt a non-planar arrangement with respect to the naphthalene core, making dihedral angles of 52.7 (1) and 54.6 (1) degree with it. The Li+ ions are tetrahedrally coordinated by carboxyl and water O atoms. The Li-O distances are in the range 1.906 (3)-2.041 (3) A, averaging 1.97 (4) A; O-Li-O angles are 101.5 (1)-123.9 (1) degree, averaging 109 (6) degrees. Each of the 12 inequivalent water H atoms is involved in hydrogen bonding. Of these bonds, 11 are typical two centered hydrogen bonds with an average H...O (acceptor) distance of 1.92 (11) A and an average O-H...O (acceptor) angle of 172 (5) degrees. One water H atom is involved in a three-centered hydrogen bond with an average H...O (acceptor) distance of 2.61 (4) A and an average O-H...O (acceptor) angle of 120 (3) degrees. Adjacent organic anions are separated by the Li+ ions and their coordination polyhedra, with the water molecules occupying positions above and below the naphthalene rings and participating in a three-dimensional hydrogen bonded network. PMID- 1418816 TI - Structure of bis(2-chloroethyl)ammonium hexachlorostannate. AB - [(ClCH2CH2)2NH2]2SnCl6, M(r) = 617.48, monoclinic, C2/c, a = 15.67 (2), b = 13.54 (2), c = 13.24 (2) A, beta = 127.9 (2) degrees, V = 2217 A3, Z = 4, D chi = 1.85 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 23.70 cm-1, F(000) = 1208, T = 295 K, R = 0.058, wR = 0.071 for 1231 unique reflections. The structure consists of discrete (ClCH2CH2)2NH2+ cations and octahedral SnCl6(2-) anions with the Sn sitting on the twofold axis. PMID- 1418817 TI - Folding, aggregation and molecular recognition in peptides. AB - In past years, most of the X-ray structure determinations of oligopeptides were for cyclic peptides or for short linear peptides. Longer peptides usually presented many difficulties in obtaining suitable crystals since the molecules are intrinsically very flexible. More recently, it has been appreciated that the aminoisobutyric acid residue (Aib), which occurs naturally in many peptides of microbial origin, initiates helix folding. Several score of 7- to 15-residue linear peptides containing Aib have been synthesized, crystallized and had their structures determined to high resolution. Many of the peptide structures have been determined in more than one crystalline form. These peptide structures have yielded a plethora of information on types of helices, modes of hydration, water penetration into helical backbones, helices bent by Pro residues, parallel and antiparallel association of helices, effects of Leu residues on association of peptides, an example of a zipper assembly by side chains, and an example of a possible ion channel with a gating mechanism. PMID- 1418818 TI - Structural studies of oxygen-bridged iron compounds. AB - Compound (I): cis-dichloro[mu-[bis[mu-[[2,6-diacetylpyridine dioximato](2-) O:O']]dihydroxodiphenyl-diborato](3-)]- mu- mithoxydiiron, [Fe2(C30H29B2N6 O6)Cl2(CH3O)], M(r) = 804.9, monoclinic, Cc, a = 21.228 (6), b = 8.020 (2), c = 20.865 (5) A, beta = 105.2 (1) degrees, V = 3428 (2) A3, Z = 4, Dx = 1.56 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 10.6 cm-1, F(000) = 1648, T = 275 K, R = 0.055 for 3018 unique reflections. Compound (I) contains a pseudo-twofold axis relating the two pyridine dioxime groups bound to the Fe atoms. In addition, two O atoms from the phenylborate moieties bridge the iron atoms, as does a methoxide. The two Cl atoms are bound to the seven coordinate metals axial to the methoxide. Compound (II): cis-dichloro[mu-[bis[mu-[[2,6-diacetylpyridine dioximato](2-)-O:O']]dihydroxodiphenyldiborato](3-)]-mu- hydroxodiiron, [Fe2(C30H29B2N6-O6)Cl2(OH)].H2O.2C2H3N, M(r) = 891.0, monoclinic, P2(1)/n, a = 11.860 (2), b = 20.911 (5), c = 16.175 (3) A, beta = 92.88 (1) degrees, V = 4006 (3) A3, Z = 4, Dx = 1.48 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 9.1 cm-1, F(000) = 1832, T = 275 K, R = 0.051 for 7034 unique reflections. Compound (II) contains a hydroxide group replacing the methoxide in compound (I). The crystals also contain two acetonitriles of solvation. The bond lengths in the complex and the hydrogen-bonding pattern in the crystals are consistent with one of the bridging borate O atoms being protonated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418819 TI - Structure of a pepsin/renin inhibitor complex reveals a novel crystal packing induced by minor chemical alterations in the inhibitor. AB - The structure determination by molecular replacement methods of a monoclinic pepsin/renin inhibitor complex crystal, with two molecules in the asymmetric unit, is presented. The atomic model, consisting of two liganded pepsin molecules and 110 water molecules, has been refined to a final crystallographic R value of 0.139 for data between 8 and 2.9 A resolution. The structure reveals a previously undescribed pepsin dimer formed predominantly by polar interactions. Inhibitor binding induces global structural changes in the native enzyme similar, but not identical, to the ones observed in other chemically similar pepsin/renin inhibitor complexes crystallized in an orthorhombic form. A region of the polypeptide chain (residues 292-297) which was not visible in the orthorhombic crystal is well ordered in the presently described structure; possibly induced by crystal contacts. The crystal packing of native pepsin is compared with the two different crystal forms of the inhibited enzyme. PMID- 1418820 TI - Structure determination of the bacteriophage phiX174. AB - The structure of the single-stranded DNA phage phiX174 has been determined to 3.4 A resolution. The crystal space group was P2(1) with one icosahedral particle per asymmetric unit, giving 60-fold noncrystallographic redundancy. Oscillation diffraction photographs were collected using synchrotron radiation at various wavelengths. The particle orientations in the unit cell were determined with a rotation function. Because cowpea mosaic virus has a similar external envelope to phiX174, it was used as a search model to find the approximately positions of the phiX174 particles in the unit cell relative to the crystallographic symmetry axes. An initial phase set to 12 A resolution was then based on the cowpea mosaic virus atomic structure. These phases were improved by 20 cycles of real-space molecular replacement averaging. The phase information was gradually extended to 3.4 A resolution by molecular replacement electron density averaging. One reciprocal lattice point was used for each extension followed by four cycles of averaging. The unusual particle capsid, with its 12 pentameric spikes, required the careful determination of a precise molecular envelope. This was redetermined at regular intervals, as was the particle center. The resultant electron density map was readily interpreted in terms of the F, G and J polypeptides in the capsid. A difference electron density map between full and partially empty particles showed some ordered DNA structure. PMID- 1418821 TI - A note on the conformational flexibility of the antiestrogenic drug tamoxifen: preferred conformations in the free state and bound to the protein calmodulin. AB - The conformational properties of the antiestrogenic drug tamoxifen, a triphenylbut-1-ene derivative, have been studied using molecular mechanics. Four distinct conformers have been identified, and the energy barriers between them have been established. The orientation of the ethyl group substituent has been examined in particular, since the lowest-energy conformers have this group orientated 180 degrees away from its position in the crystal structures of tamoxifen and its derivatives. These differences have implications for the interactions of tamoxifen with the calcium-binding protein calmodulin; relevant results from a molecular-modelling study of this protein-drug complex are presented. PMID- 1418822 TI - Crystallization and preliminary data analysis of Flock House virus. AB - Flock House virus, purified from infected cultured Drosophila cells, crystallizes into three different forms under identical growth conditions. Two crystal forms grow in the trigonal space group R3, both with equivalent cell constants a = 323.6 A, alpha = 61.7 degrees. The difference between the two trigonal crystal forms is 1.1 degrees in the orientation of the virus particle as determined from the rotation function. Early crystal setups grew in one form, while recent crystals grew in the other form. The third space group, which accounts for 5% of the observed crystals and grows with both trigonal forms, is orthorhombic I222 with cell parameters a = 416.7, b = 332.1, c = 351.2 A. The trigonal crystal forms contain one virion per unit cell and the orthorhombic form contains two particles per cell. All three crystal forms diffract X-rays to 2.8 A resolution. PMID- 1418824 TI - Pancreatic ribonuclease co-crystallizes with the dinucleotide dCpdG in two distinct forms. PMID- 1418823 TI - Structure determination of a dimeric form of erabutoxin-b, crystallized from a thiocyanate solution. AB - Erabutoxin-b, M(r) = 6861.1, a single 62 amino-acid chain folded by four disulfide bridges, was crystallized in a new orthorhombic form by using thiocyanate as crystallizing agent. The space group is P2(1)2(1)2(1) with a = 53.36 (4), b = 40.89 (4), c = 55.71 (5) A, V = 121533.1 A and Z = 8. X-ray diffraction data were recorded at the LURE synchrotron facility (lambda = 1.405 A). The structure was solved by molecular replacement and shows a dimeric association through an anti-parallel beta-sheet around the twofold non crystallographic axis. The two independent molecules, one SCN- ion and 97 associated water molecules were refined by molecular dynamics and annealing techniques to R = 19.6% (10,913 Fobs, resolution 5-1.7 A). The thiocyanate ion is located at the interface of the dimer and close to the non-crystallographic twofold axis. PMID- 1418825 TI - The structure determination of Sindbis virus core protein using isomorphous replacement and molecular replacement averaging between two crystal forms. AB - The structure of Sindbis virus core protein has been determined by a combination of multiple isomorphous replacement and molecular replacement averaging techniques. The multiple isomorphous replacement phase determinations were made for two crystal forms (P2(1) and P4(3)2(1)2) of the core protein. The real-space molecular replacement averaging was subsequently carried out between two copies of the protein per asymmetric unit in the monoclinic form and one copy in the tetragonal form. This greatly improved the quality of the electron density maps. The Sindbis virus core protein polypeptide could be traced and related to the known amino acid sequence. The averaging procedure between different crystal forms, as described in this paper, should be generally applicable to other systems. PMID- 1418826 TI - Dynamical scattering and electron crystallography--Ab initio structure analysis of copper perbromophthalocyanine. AB - Electron diffraction intensity data were collected at 1200 kV from thin epitaxially oriented crystals of copper perbromophthalocyanine (C32Br16CuN8) in a projection down molecular columns. Measured cell constants for the projection with cmm symmetry are d100 = 17.88 (9), b = 26.46 (15) A. The structure was determined by Fourier refinement after three heavy-atom positions were identified in an initial potential map. In addition to the copper and halogens, all light atom positions were found. Although the final R value for all data is 0.41, n beam dynamical calculations for crystal thicknesses corresponding to the estimated sample dimension account for the observed amplitudes that deviate most from their kinematical values. PMID- 1418827 TI - Conjugate-direction minimization: an improved method for the refinement of macromolecules. AB - A novel method of function minimization that combines the power of the diagonal approximation to the normal matrix with conjugate directions is described. This method approaches closer to the local minimum than the methods that are commonly used in macromolecular refinement. The weakness of the current methods are analyzed to explain the advantage of the conjugate-direction method. PMID- 1418828 TI - A consistent model of insulin-dependent diabetes mellitus hypertension. AB - Hypertension is frequently seen in insulin-dependent diabetes mellitus (IDDM), but the mechanism of the hypertension is unknown. An animal model of IDDM hypertension could be helpful in determining the mechanism, but experimental IDDM has been infrequently and irregularly associated with hypertension. In an attempt to develop a consistent model of IDDM hypertension, we superimposed streptozotocin (STZ)-induced IDDM on surgical reduction of renal mass (RRM) in Wistar rats. Seven groups of rats were studied: 1) 60% RRM receiving 65 mg/kg body weight (BW) STZ; 2) 60% RRM receiving 40 mg/kg BW STZ; 3) 25% RRM receiving 65 mg/kg BW STZ; 4) two kidney normal rats receiving 65 mg/kg BW STZ; 5) 60% RRM receiving vehicle (control for group 1); 6) 60% RRM receiving vehicle (control for group 2); and 7) 25% RRM receiving vehicle. STZ produced diabetes and hypertension within 1 to 2 weeks in all three groups of RRM rats but blood pressure was unaffected by 60% or 25% RRM alone. STZ alone had no effect on blood pressure until the 5th week when the blood pressure increased slightly. Progressive weight loss resulted from 65 mg/kg BW STZ combined with 60% RRM; the animals had to be terminated after 5 weeks. In only 60% of animals with 40 mg/kg BW STZ plus 60% RRM was IDDM produced. On the other hand, 65 mg/kg BW STZ in rats with 25% RRM regularly produced IDDM and hypertension without excessive loss of body weight. In these rats, albuminuria developed in 2 weeks. Extracellular fluid volume was elevated and plasma renin activity was depressed. The animals were healthy and hypertensive when killed at the 13th week. We suggest that the 25% RRM rat receiving 65 mg/kg BW STZ is a consistent model of IDDM hypertension, which may be useful in probing the mechanism of this type of hypertension. PMID- 1418829 TI - Chronic magnesium administration enhances oxidative glucose metabolism in thiazide treated hypertensive patients. AB - In newly-diagnosed untreated (n = 24) and thiazide treated (n = 18) hypertensive patients erythrocyte ion content and plasma ion and metabolite levels were determined. Thiazide treated patients had lower arterial blood pressure, plasma ion levels, erythrocyte magnesium and potassium content but higher fasting plasma insulin (66 +/- 7 v 87 +/- 8 pmol/L P < .02), triglycerides (1.88 +/- 0.24 v 2.34 +/- 0.44 mmol/L P < .05), free fatty acids (0.68 +/- 0.11 v 0.81 +/- 0.18 mmol/L P < .05). Subsequently, in a double-blind fashion and in random order thiazide diuretic treated patients were assigned to two groups: the first (n = 9) taking magnesium (15.8 mmol/day) and the other (n = 9) a placebo. Each treatment period lasted 8 weeks. At the end of each treatment period, each patient underwent blood sampling for determination of erythrocyte ion content and plasma ion and metabolite levels and was submitted to an euglycemic hyperinsulinemic (1 mU/kg/min for 120 min) glucose clamp. In this latter test D-3-H glucose infusion and indirect calorimetry allowed determination of glucose turnover parameters and substrate oxidation respectively. Chronic magnesium administration (CMA) raised fasting plasma (0.79 +/- 0.03 v 0.83 +/- 0.02 mmol/L, P < .05) and erythrocyte (1.98 +/- 0.08 v 2.35 +/- 0.03 mmol/L, P < .01) magnesium content. Along with insulin infusion, CMA improved glucose uptake, glucose metabolic clearance rate, and oxidative glucose metabolism. In the multiple linear regression analysis of the pooled basal data (n = 42), erythrocyte magnesium content displayed an independent correlation with basal plasma insulin levels (t = -2.08, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418830 TI - Effects of aging and hypertension on plasma angiotensin II and platelet angiotensin II receptor density. AB - Plasma renin activity (PRA) declines with age in normal individuals, but the effect of age on plasma angiotensin II (ANG II) is less clear. A decline in plasma ANG II with age could result in altered platelet ANG II receptor density since plasma hormone levels influence their target organ receptors. To investigate this possibility, PRA, plasma ANG II, and platelet ANG II receptor density were examined in 17 young, 12 middle-aged, and 14 elderly healthy normotensive volunteers. To assess whether hypertension altered receptor density, these variables were also examined in 23 hypertensive patients. In normotensives, there was a negative correlation between age and PRA (r = -0.43, P < .05), no significant change in basal plasma ANG II with age, and a weak positive correlation between age and ANG II receptor density (r = 0.34, P < .05). Multiple regression analysis revealed that the relationship between age and ANG II receptor density was independent of the associated rise in mean arterial pressure with age (P < .05). Platelet ANG II receptor density was not significantly related to PRA or plasma ANG II. ANG II receptor affinity did not change with age. Neither PRA nor ANG II receptor density or affinity differed between hypertensives and normotensives of similar mean age, but plasma ANG II was significantly lower in hypertensives compared with normotensives. We concluded that aging is associated with a decline in supine PRA. The small decrease in plasma ANG II was not significant. Platelet ANG II receptor density increased with age primarily due to a small group of elderly subjects with elevated receptor density. There was no change in ANG II receptor density or affinity in hypertensives despite apparently lower plasma ANG II in these patients. PMID- 1418831 TI - Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension. AB - Various facets of glucose, insulin, and lipid metabolism were compared in 76 normal volunteers--38 with and 38 without a family history of hypertension. The two groups were comparable in terms of age, gender distribution, and degree of obesity (both generalized and abdominal). Although the plasma glucose response to oral glucose was similar in both groups, glucose-stimulated insulin concentrations were significantly greater in volunteers with a family history of hypertension (P < .001). Furthermore, the steady state plasma glucose concentration during a constant infusion of glucose, insulin and somatostatin was significantly greater in subjects with a family history of hypertension (8.1 +/- 0.6 v 6.2 +/- 0.6 mmol/L, P < .001). Since the steady-state plasma insulin levels during the infusion were similar, these results indicate that normotensive individuals with a family history of hypertension are relatively insulin resistant. Finally, plasma very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol were higher in those with a family history of hypertension, as was the ratio of total to high density lipoprotein cholesterol. Thus, normotensive individuals with a family history of high blood pressure are insulin resistant, hyperinsulinemic and dyslipidemic when compared to a matched group of healthy volunteers without a family history of hypertension. PMID- 1418833 TI - Higher salt consumption, digoxin-like factor, and nifedipine response are associated with salt sensitivity in essential hypertension. AB - In addition to demonstrating evidences of increased sympathetic nervous system activity and marked left ventricular hypertrophy in salt-sensitive hypertensives, our group has also reported increased weight gain with salt overload in these patients. The increased weight gain suggests volume expansion, a situation already shown to increase plasma levels of a Na, K-ATPase inhibitor. Therefore, in the present study, digoxin-like factor (DLF) serum levels, spontaneous salt ingestion, nifedipine hypotensive effect, and plasma renin activity were evaluated in essential hypertensive subjects. Thirteen essential hypertensive outpatients were studied sequentially on an ad lib diet, a low salt diet (LSD = 30 mEq Na/day), and a high salt diet (HSD = LSD + 171 mmol/L NaCl/day), 1 week each. On the seventh day of LSD and HSD, DLF levels, mean blood pressure (MBP) response to nifedipine (10 mg sublingual), and plasma renin activity were measured. The MBP percent change from the seventh day of LSD to the seventh day of HSD (salt sensitivity) ranged from -13.7 to 20.9%. A positive correlation (r = 0.64, P < .01) was observed between salt sensitivity and 24-h urinary sodium excretion with an ad lib diet. The DLF serum levels correlated with the salt sensitivity both on LSD (r = 0.50, P < .05) and on HSD (r = 0.53, P < .05). Salt sensitivity was positively correlated with the difference of response to nifedipine between HSD and LSD (r = 0.78, P < .001). Plasma renin activity correlated inversely with DLF on LSD (r = -0.51, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418832 TI - Effect of extracellular magnesium on platelet activation and intracellular calcium mobilization. AB - A dose-dependent effect of magnesium on the inhibition of platelet aggregation and release of ATP from dense granules was observed in human platelets (in whole blood, platelet-rich plasma, or washed platelets) against various aggregation agents (ADP, U46619, collagen, or thrombin). The synthesis and release of the proaggregatory cyclooxygenase (CO) and lipoxygenase (LO) products, thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively, in platelets were also inhibited by Mg in a dose-dependent manner (IC50 4 to 6 mmol/L). These Mg-mediated activities were further enhanced when platelets were preincubated with insulin (100 microU/mL). The effect of extracellular Mg on the change of intracellular calcium concentration ([Ca2+]i) was assessed using Fura-2/AM loaded cells in the presence or absence of extracellular Ca. Thrombin-stimulated influx of Ca ions decreased from 194 +/- 30 nmol/L to 156 +/- 21 nmol/L in the presence of 5 mmol/L Mg and to 111 +/- 16 nmol/L in 10 mmol/L Mg. However, the intracellular Ca release (as determined in the presence of 5 mmol/L EGTA) was not affected by Mg. The intracellular Ca-dependent protein kinase C and myosin light chain kinase activities on the phosphorylation of endogenous p47 and p20 proteins studied after 2 min of thrombin addition decreased only 10 to 25% in the presence of 5 to 10 mmol/L Mg. Similar results were obtained when EGTA was added prior to the initiation of protein phosphorylation. We conclude that Mg can dose dependently inhibit a wide variety of agonists on platelet aggregation. Furthermore, insulin can potentiate the inhibitory effects of Mg on platelet activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418834 TI - The effect of acute and chronic hematocrit changes on cardiovascular hemodynamics in spontaneously hypertensive rats. AB - Heparin given over a long term by a subcutaneous route consistently lowers blood pressure in the hypertensive rat models. The decrease in blood pressure is accompanied by a parallel decrease in hematocrit suggesting a causal relationship between hematocrit and blood pressure. The aim of this study was to define the relationships between acute and chronic hematocrit changes and blood pressure in the normotensive and hypertensive states. Normotensive Wistar (NWR) and spontaneously hypertensive (SHR) rats were used. Hematocrit was decreased acutely by blood-letting, and chronically by treatment with either heparin (H) or phenylhydrazine (P) for 4 weeks. Acute and chronic hematocrit increase was accomplished by packed cells transfusion. Systolic blood pressure was measured weekly; and at the end of the experimental period, plasma volume, cardiac output, and mean arterial pressure were obtained. Acute hematocrit decrease or increase (hematocrit ranging from 25 to 65%) did not affect blood pressure in either strain of rats; whereas chronic hematocrit changes (hematocrit ranging from 35 to 61%) significantly affected blood pressure only in SHR. Thus, chronic hematocrit decrease induced by H or P resulted in a significant fall in blood pressure compared to control (201 +/- 3 v 175 +/- 4, 167 +/- 4 mm Hg, respectively; P < .05). Conversely, a chronic hematocrit increase resulted in a significant rise in blood pressure (201 +/- 3 v 219 +/- 4 mm Hg; P < .05). Similar hematocrit changes produced in NWR, as in SHR, did not affect blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418835 TI - The accuracy and performance of the A&D TM 2421, a new ambulatory blood pressure monitoring device based on the cuff-oscillometric method and the Korotkoff sound technique. AB - The accuracy and performance of the A&D TM 2421, a new ambulatory blood pressure (BP) monitoring device using both the cuff-oscillometric method (O) and the Korotkoff sound method (K) were evaluated. The device was tested for accuracy under static and dynamic conditions by simultaneous comparison with two observers using a standard mercury column sphygmomanometer (standard method) and by the objective recording method (ORM). The performance of the device was also evaluated under ordinary ambulatory conditions. The mean differences in BP of standard method from K-method were -1.2 +/- 4.7 mm Hg systole and 1.3 +/- 4.7 mm Hg diastole (n = 323, mean +/- SD) and those of standard method from O-method were -0.4 +/- 5.3 mm Hg systole and 1.4 +/- 5.1 mm Hg diastole (n = 323). The agreement between each of the two methods of the device and the standard method was within 10 mm Hg for more than 90% of both systolic and diastolic readings. During bicycle exercise, the mean differences in BP of standard method from K method were -3.4 +/- 4.8 mm Hg systole and 1.8 +/- 5.2 mm Hg diastole (n = 71) and those of standard method from O-method were -1.1 +/- 7.3 mm Hg systole and 1.7 +/- 7.8 mm Hg diastole (n = 67). There was a greater scatter in the individual comparisons of the device and the standard method during exercise, especially in diastolic BP. The relation between the device and ORM was almost similar to that between the device and the standard method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418837 TI - NMR measurement of intracellular potassium in the perfused normotensive and spontaneously hypertensive rat aorta by a multinuclear subtraction procedure. AB - Intracellular free potassium ion concentrations have been measured in the isolated perfused aortae from Wistar-Kyoto and spontaneously hypertensive rats by a novel multinuclear NMR procedure, which allows the estimation and subtraction of the extracellular potassium signal from the total 39K+ resonance. When tested on a sample of erythrocytes, the method yielded an intracellular potassium concentration of 149 mmol/L cell water, which is similar to the previously reported average of 140 mmol/L cell water, indicating full (100%) NMR "visibility" of red cell 39K+. In contrast, the 39K+ resonance of the perfused rat aorta preparation indicated very low (approximately 15%) NMR visibility of intracellular potassium in the aortic tissue, similar to that previously reported for perfused hearts. More importantly, aortae from spontaneously hypertensive rats yielded a corrected (for low NMR visibility) intracellular potassium concentration of only 90 +/- 10 (mean +/- SE; n = 6) mmol/L cell water, which was significantly lower (40%; P = .02) than that in aortae from normotensive rats. The NMR data thus reveal a significant depletion of intracellular potassium in hypertensive arterial smooth muscle cells. PMID- 1418836 TI - A randomized, placebo-controlled, double-blind comparison of amlodipine and atenolol in patients with essential hypertension. AB - The efficacy and safety of amlodipine (2.5 mg, 5 mg, or 10 mg) once daily was compared with atenolol (50 mg to 100 mg) once daily in patients with mild-to moderate essential hypertension in a randomized, double-blind, parallel, placebo controlled study. One hundred and twenty-five patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks' double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The mean changes from baseline in blood pressure 24 h postdose for amlodipine (mean daily dose 8.8 mg) were -12.8/-10.1 mm Hg for supine and -11.5/-9.8 mm Hg for standing blood pressure (P < .001). For atenolol (mean daily dose 83.7 mg) the changes were 11.3/-11.7 mm Hg for supine and -13.3/-12.3 mm Hg for standing blood pressure (P < .001). There were no statistically significant differences between treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1%, 64.9%, and 11.1%, respectively. Determinations taken over the 24-h period at the final visit revealed that amlodipine and atenolol maintained the group mean supine blood pressure at or below 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Heart rate was significantly lowered by atenolol only. Both amlodipine and atenolol were well-tolerated. Only one patient was withdrawn because of the development of peripheral edema, arthralgia, and fatigue after treatment with amlodipine. This study demonstrates that once-daily administration of amlodipine or atenolol to mild-to-moderate hypertensive patients was well tolerated and provided adequate blood pressure control throughout the 24-h dosing interval. PMID- 1418838 TI - Noninvasive automatic blood pressure monitoring does not attenuate nighttime hypotension. Evidence from 24 h intraarterial blood pressure monitoring. AB - Automatic ambulatory blood pressure monitoring makes use of repeated cuff inflations throughout the day and night. This may interfere with the cardiovascular effects of sleep and thus alter the 24 h blood pressure profile. The possibility that intermittent automatic blood pressure measurements prevent nocturnal hypotension was examined in 17 mild or moderate essential hypertensive patients in whom blood pressure was recorded intraarterially for 48 h by the Oxford technique. During the first or the second 24 h period, blood pressure was also monitored noninvasively by the SpaceLabs (Redmond, WA) 5300 (n = 10) and by the Sandoz Pressure System SPS 1558 (Lavanchy Electronique, Prilly, Switzerland) (n = 7) devices, automatic measurements being performed at 15 min intervals during the day and at 30 min intervals during the night. Separate computer analysis of 24 h intraarterial tracings obtained in absence and in concomitance of contralateral automatic blood pressure monitoring showed that the occurrence of automatic measurements had not interfered with the day-night intraarterial blood pressure and heart rate profiles. Thus the frequent cuff inflations that characterize automatic blood pressure monitoring do not attenuate nighttime hypotension and bradycardia. This finding supports use of the noninvasive approach in assessing blood pressure profiles. PMID- 1418839 TI - Decreased rates of release of atrial natriuretic peptide from isolated hearts from aging hypertensive rats. AB - We tested the hypothesis that in genetically hypertensive New Zealand rats left ventricular hypertrophy predisposes to left atrial disease and should be associated with a decreased release of atrial natriuretic peptide (ANP) in response to acute left atrial stretch. Abrupt distention of the left atrium was achieved by the acute onset of left atrial distention in Langendorff-perfused isolated rat hearts, which resulted in a rapid release of ANP in all groups of hearts. Comparisons were made between normotensive and hypertensive hearts using rats aged 2 months, 8 months, 12 months, and 16 months. Rates of release of ANP from normotensive and hypertensive hearts were similar at 2 months. Thereafter, there was a progressive impairment of ANP release, until in rats aged 16 months, rates of release achieved in hypertensive hearts 2 min after the onset of left atrial distention were only about half of those of normotensive hearts (55%, P < .005). At all ages above 2 months, hypertensive hearts failed to increase the concentration of ANP in the coronary effluent at the onset of increased heart work. Therefore, in rats with genetic hypertension, there is an impairment of release of ANP from the isolated heart in response to left atrial distention. PMID- 1418840 TI - Disparate effects of weight loss on insulin sensitivity and erythrocyte sodium lithium countertransport activity. AB - Previous investigations have demonstrated an association between impaired insulin sensitivity and elevated erythrocyte sodium-lithium countertransport (Na(+)-Li+ CT) activity. It has been speculated that insulin resistance and endogenous hyperinsulinemia are causally related to the development of elevated Na(+)-Li+ CT activity. To test this hypothesis, we measured insulin sensitivity (euglycemic insulin clamp technique) and Na(+)-Li+ CT activity in eight obese women before (weight = 102 +/- 5 kg) and after (weight = 88 +/- 5 kg; P < .001) a 10 week weight reduction program. Maximal velocity of Na(+)-Li+ CT activity did not change (0.50 +/- 0.09 v 0.49 +/- 0.10 mmol/L red blood cells/h; P = NS) despite the significant improvement in insulin sensitivity (73 +/- 12 vs 110 +/- 7 mg/m2/min; P < .0025) and reduction in fasting insulin levels (17 +/- 2 v 10 +/- 2 microU/mL; P < .05) that accompanied weight loss. These results suggest that insulin resistance and hyperinsulinemia are not linked pathophysiologically to the development of elevated Na(+)-Li+ CT activity. PMID- 1418842 TI - Twenty-four hour ambulatory blood pressure profiles following regular alcohol consumption. PMID- 1418841 TI - Cellular basis of ventricular remodeling in hypertensive cardiomyopathy. AB - This review summarizes the effects of long-term pressure overload hypertrophy on the right and left ventricular myocardium. In particular, the role that the fundamental processes of myocyte growth plays in the remodeling of the wall is analyzed quantitatively. Moreover, emphasis is placed on the observation that the duration of the overload is an important component of the onset, development, and progression of time-dependent myocardial dysfunction associated with hypertensive cardiomyopathy. The deterioration in ventricular pump function is postulated to be accompanied by myocyte cellular hyperplasia and capillary proliferation in an attempt to increase the thickness of the ventricular wall and, consequently, to decrease the magnitude of systolic and diastolic stress generated by the elevation in ventricular systolic and end-diastolic pressures. Myocyte cellular hyperplasia constitutes an essential growth reserve mechanism of the heart. Regeneration of damaged and lost myocardium may be accomplished by hyperplasia of myocytes, a phenomenon considered not feasible for several decades. PMID- 1418843 TI - Endothelin-1 and blood pressure. PMID- 1418844 TI - Antihypertensive drug therapy and insulin resistance. PMID- 1418845 TI - Questions and answers from controlled clinical trials of antihypertensive therapy in progressive renal disease. PMID- 1418846 TI - Mild essential hypertension in nonobese premenopausal women is characterized by low renin. AB - The pathophysiological mechanisms in hypertension may differ in men and women. Plasma renin activity was measured in 27 premenopausal, never-treated hypertensive women (blood pressure 141 +/- 2/93 +/- 1 mm Hg) and in 18 age matched normotensive women (blood pressure 113 +/- 2/71 +/- 2 mm Hg). All subjects were unaware of their blood pressure status. The hypertensive women had on average lower plasma renin activity (0.21 +/- 0.03 nmol/L/h) than their normotensive controls (0.42 +/- 0.07 nmol/L/h, P less than .01). Serum estradiol was also lower in the hypertensive women (0.57 +/- 0.06 v 0.81 +/- 0.09 nmol/L, P less than .05). No difference in epinephrine, norepinephrine, atrial natriuretic peptide, or vasopressin was found between the groups. Plasma renin activity was positively correlated to plasma norepinephrine in the hypertensive women only (r = 0.41, P less than .05). Since low renin hypertension is associated with less cardiovascular complications, this may offer an explanation for the better prognosis of hypertension in women. PMID- 1418847 TI - High sucrose diets increase blood pressure of both salt-sensitive and salt resistant rats. AB - We examined the effects of a diet relatively high in sugar and low in protein content on systolic blood pressure (SBP) in rats with known pressure responses to salt (NaCl) in order to compare "sugar/protein sensitivity" to "salt sensitivity." Dahl salt-sensitive (DSS) and salt-resistant (DSR) rats were fed one of two low salt diets containing either high sugar (sucrose 51.5% w/w)/low protein (14.6% w/w) or low sugar (sucrose 12.5% w/w)/high protein (52.2% w/w) content. After 3 weeks, the DSS ingesting the high sugar diet/low protein diet developed significantly elevated SBP relative to DSR eating the same high sugar/low protein diet and the DSS and DSR consuming the low sugar/high protein diet. After 2 to 3 months, the SBP of DSR eating the high sugar diet began to rise markedly and eventually both DSS and DSR ingesting the high sugar/low protein diet maintained similarly elevated SBP, significantly higher than DSS and DSR ingesting the low sugar/high protein diet. When Fischer 344 rats, a normotensive, salt-resistant rat strain, were fed the high sucrose/low protein diet, SBP also rose significantly into hypertensive ranges over 2 to 3 months. Since the SBP of DSR and Fischer 344 rats are not influenced to any great extent by high salt intake, even after prolonged exposure, the SBP rise associated with the high sugar/low protein diet may be via a mechanism different from salt induced hypertension. However, it is also possible that the high sugar/low protein diet creates in DSS and DSR the situation responsible for salt induction in DSS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418848 TI - Natriuretic hormones in young hypertensives and in young normotensives with or without a family history of hypertension. AB - The behavior of plasma atrial natriuretic factor (ANF) and digoxin-like substance (DLS), and the daily urinary excretion of kallikrein (uKK) were evaluated in young hypertensives and in young normotensives with or without a family history of essential hypertension. Each group was also evaluated, separating those with low plasma renin activity from the total sample. The sample group was made up of 75 young males; 31 hypertensives (mean age 22.7 +/- 2.5 years), 28 normotensives with hypertensive heredity (normotensives F+) (mean age 22.2 +/- 1.9 years) and 16 normotensives (mean age 22.0 +/- 2.1 years). An inverse correlation between ANF and PRA was shown in all groups. In hypertensives, ANF was inversely correlated with uKK (r = -0.664, P less than .0001). Plasma ANF (P less than .012) and DLS (P less than .0001) were higher in hypertensives than in normotensives, while uKK excretion was lower (P less than .0001). Plasma levels of DLS were higher in F+ normotensives than in normotensives (P less than .003). Low renin hypertensives showed the lowest uKK excretion (P less than .0001 v normal-high renin hypertensives). Furthermore, low renin hypertensives showed the highest plasma levels of ANF (P less than .0001 v normal high renin hypertensives) and DLS (P less than .012 v normal-high renin hypertensives). Plasma ANF (P less than .0001) was higher, while uKK was lower (P less than .045) in low renin F+ normotensives than in normal-high renin ones. In conclusion, our data indicate that plasma ANF and DLS are elevated since the early phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418849 TI - Community-based epidemiological study on hypertension in Pu-Li, Taiwan. AB - A community-based study was carried out by the Yang-Ming Crusade in 1987-1988 in Pu-Li Town, Taiwan. We interviewed 1738 out of 2573 registered residents more than 30 years old and their fasting blood samples were drawn and tested. The prevalences of definite hypertension (greater than or equal to 160/95 mm Hg) and borderline hypertension (140/90 to 160/95 mm Hg) were 18.7% and 16.0%, respectively. To study factors associated with hypertension, univariate analysis was applied first. Stratified analyses by age and sex were used for interaction assessment. Logistic regression was used for multivariate analysis. According to the final model, the significant factors related to definite hypertension were age (greater than or equal to 50 v less than 50 years of age, odds ratio [OR] 2.6, 95% confidence interval [CI] 1.6 to 4.3), physical activity (frequent v infrequent, OR 0.4, 95% CI 0.2 to 0.6), alcohol intake (yes v no, OR 2.3, 95% CI 1.1 to 4.6), and cholesterol (greater than or equal to 240 v less than 240 mg/dL, OR 1.7, 95% CI 1.0 to 2.9). Significant factors related to borderline hypertension were age (only for those cholesterol greater than or equal to 240 mg/dL, greater than or equal to 50 v less than 50 years of age, OR 4.1, 95% CI 2.1 to 7.9), cholesterol (only for those age less than 50, greater than or equal to 240 v less than 240 mg/dL, OR 3.6, 95% CI 1.6 to 7.8), physical activity (frequent v infrequent, OR 0.4, 95% CI 0.2 to 0.7), and alcohol intake (yes v no, OR 2.3, 95% CI 1.1 to 4.6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418850 TI - Ambulatory blood pressure monitoring in a nonacademic setting. Effects of age and sex. AB - Twenty-four-hour ambulatory blood pressure measurements (ABPM) are likely to eliminate the stress of visits and observer bias in office blood pressure (BP) recordings, allow consideration of the circadian variability in BP, and correlate well with target organ damage. To define the prevalence of "white coat" hypertension in a rural community to a nonacademic setting, and to assess age and sex related differences, we studied 131 patients who had more than two prior office diastolic BP measurements greater than 90 mm Hg and less than 115 mm Hg. Blood pressure was measured every 10 to 60 min for 24 h using the SpaceLabs 90207 device. Office BP readings were higher than ABPM in the group as a whole, in individual age groups, and in both sexes. The differences were more pronounced at night. Average differences between office and ambulatory BP ranged between 14.4 +/- 1.7/2.9 +/- 2.0 (ABPM at 10:00), and 33.8 +/- 2.3/22.8 +/- 1.5 mm Hg (systolic/diastolic +/- SE) (ABPM at 01:00). The nighttime drop in systolic BP was not apparent in subjects more than 65 years old. Women had a proportionately higher mean office BP than men (115.0 +/- 0.9 office v 110.2 +/- 1.3 mm Hg ABPM in women and 112.3 +/- 0.9 v 104.3 +/- 1.1 mm Hg in men) (P = .013), and the elderly did not display the relationship between ambulatory and office mean BP seen in younger subjects (r = 0.15, P = .30 v r = 0.36, P = .0004, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418851 TI - Mechanisms involved in the progression to glomerular sclerosis induced by systemic hypertension during mild puromycin aminonucleoside nephrosis. AB - To evaluate the contribution of systemic hypertension in the progression of nephropathies to glomerular sclerosis, a mild form of puromycin aminonucleoside (PAN) nephrosis was associated with Goldblatt hypertension and studied after 18 weeks. We studied four groups: Group I, controls; Group II, Goldblatt hypertension; Group III, PAN nephrosis; and Group IV, both conditions. Systolic blood pressure, 24-h proteinuria, serum cholesterol, triglycerides, glomerular hemodynamics, and histological studies were compared among the groups. Rats in groups II and IV developed systemic hypertension, but only group IV rats showed persistent proteinuria. No alterations in lipid metabolism were present in any of the groups. The most striking findings in the micropuncture studies were a significant increase of glomerular capillary pressure in group IV rats (63.15 +/- 1.34 mm Hg) as compared to controls (48.74 +/- 0.97 mm Hg) and to groups II and III (55.31 +/- 2.11 and 48.17 +/- 1.23 mm Hg, respectively), and a marked fall in Kf in groups III and IV. Only group IV showed significant histological alterations such as glomerular sclerosis, interstitial damage, and increased glomerular area. These results suggest that, in the presence of an underlying nephropathy, a greater fraction of systemic pressure is transmitted to the glomerular capillaries when systemic hypertension is present; the resulting elevation in glomerular pressure and proteinuria seems to be responsible for the progression to glomerular sclerosis. PMID- 1418852 TI - Insulin-stimulated vascular relaxation. Role of Ca(2+)-ATPase. AB - We have recently described defects in vascular smooth muscle Ca2+ transport in insulin-resistant states. Since insulin stimulates plasmalemmal Ca(2+)-ATPase activity in some tissues, loss of this stimulation in insulin resistance may result in reduced Ca2+ efflux, and, consequently, increased intracellular Ca2+ and vascular tone. Consequently, the present studies were conducted to determine the effects of insulin on vascular smooth muscle Ca2+ efflux and vascular relaxation following vasoconstriction, and to determine whether these effects are attributable to insulin stimulation of Ca(2+)-ATPase. Endothelium-denuded rat aortic strips were incubated for 1 h in the presence or absence of insulin (0.1 mU/mL), and 45Ca2+ efflux was measured. In some experiments, either a low Na+ (3 to 5 mmol/L) medium was used to inhibit Na+/Ca2+ exchange, vanadate (1 mmol/L) was added to inhibit Ca(2+)-ATPase activity, or the insulin level was varied (0.01 to 1.00 mU/mL) to establish dose dependence. To determine the effects of insulin on vascular relaxation, endothelial denuded aortic strips were suspended in a muscle bath and connected to an isometric force transducer. The strips were incubated with insulin (0.1 U/mL) or vehicle for 1 h, contracted with phenylephrine, and the rate of spontaneous relaxation following phenylephrine washout was measured. Insulin (0.1 mU/mL) stimulated both Ca2+ efflux (efflux rate constant = 0.288 +/- 0.038 v 0.361 +/- 0.036 min-1 in control and insulin treated strips, respectively; P less than .005) and relaxation rate (3.97 +/- 0.35 v 4.63 +/- 0.31%/min; P less than .01), and both of these effects were inhibited by vanadate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418853 TI - Facilitatory effects of diltiazem on dopamine release in the central nervous system. Focus on interactions with D2 autoreceptors and guanosine triphosphate binding proteins. AB - The purpose of the present study was to investigate the effects of a Ca antagonist (diltiazem) on dopamine release in the central nervous system. Rat striatal slices prelabeled with [3H]dopamine (DA) and superfused with Krebs Ringer solution were stimulated electrically at a frequency of 1 Hz. Exposure to diltiazem (3.3 x 10(-7) to 1 x 10(-5) mol/L) significantly increased both the basal and stimulation-evoked [3H]DA release in a dose-dependent manner. Exogenously applied unlabeled DA inhibited the stimulation-evoked [3H]DA release. Diltiazem significantly antagonized the capacity of the unlabeled DA to inhibit stimulation-evoked [3H]DA release. The blockade of D2 receptors by a preferential D2 antagonist, sulpiride, reduced the facilitatory effect of diltiazem on stimulation-evoked [3H]DA release. Pretreatment with pertussis toxin, which interferes with the coupling of the inhibitory guanosine triphosphate-binding proteins to adenylate cyclase, significantly diminished the effects of diltiazem on stimulation-evoked [3H]DA release. These results show that diltiazem increased DA release in rat striatum, at least partially by interactions with the D2 autoreceptors and pertussis toxin-sensitive guanosine triphosphate-binding proteins. PMID- 1418854 TI - AT1 receptors mediate the release of prostaglandins in porcine smooth muscle cells and rat astrocytes. AB - Angiotensin II (AII) can release arachidonic acid metabolites such as prostacyclin (PGI2) and PGE2 from cells in cultures. It has recently been reported that the AT1 selective nonpeptide AII receptor antagonist losartan had similar effects. The present study was undertaken to further evaluate the effects of AII and losartan on cells which synthesize prostaglandins, including vascular smooth muscle, endothelial, and glial cells. Inhibition of specific [125I]AII binding was demonstrated in porcine smooth muscle cell (PSMC) suspensions with unlabeled AII and losartan. The IC50 values were 1.3 x 10(-9) mol/L and 7.7 x 10( 9) mol/L, respectively. PD123177 (an AT2 selective antagonist) had no effect on binding. AII produced a concentration-related increase in calcium mobilization (fura-2 fluorescence) which was blocked by losartan (IC50 = 8.4 x 10(-8) mol/L) but not by PD123177 (10(-6) mol/L). AII (10(-7) to 10(-5) mol/L) stimulated the basal release of PGI2 by 100%. This response was blocked by losartan (10(-6) to 10(-5) mol/L) but not by PD123177 (10(-6) to 10(-5) mol/L) and neither agent stimulated basal release in PSMC. Similar effects of AII and antagonists were observed upon receptor binding and PGE2 release in primary rat astrocyte (RA) cultures. AII did not release PGI2 from porcine endothelial cells, bovine pulmonary arterial endothelial cells, or rat C6 glioma cells. Losartan had no significant effect at 10(-5) mol/L. By contrast, bradykinin or the calcium ionophore A23187 dramatically increased PGI2 release in each of these cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418855 TI - Low sodium diet in essential hypertension. Effect on blood cell ions and hemodynamic parameters. AB - The influence of salt restriction for 3 months on blood pressure, peripheral vascular resistance (observed by occlusive plethysmography), erythrocyte sodium, platelet calcium, and pH, was studied in eight untreated essential hypertensive patients. A low salt diet decreases blood pressure, vascular resistances, erythrocyte sodium, and platelet calcium, but not platelet pH. A strong positive correlation was noted between baseline platelet calcium and vascular resistances (r = 0.95, P less than .01). But during the salt restriction period, a negative correlation has been observed between the changes in these parameters, which casts doubt on the use of the platelet as a model of the smooth muscle cell. PMID- 1418856 TI - Hypertension, diuretics, and coronary heart disease: a case of apples and oranges, reciprocal prejudice, and a partially-clad emperor? PMID- 1418857 TI - Reply to Kaplan: Coronary Heart Disease Policy Model. PMID- 1418858 TI - What is the best therapy? PMID- 1418860 TI - Differential potentiation by calcium antagonists of neuromuscular blockade induced by pancuronium and succinylcholine in cats in vivo. AB - The effects of several calcium antagonists (verapamil, nicardipine and two diltiazem isomers, d-cis and l-cis diltiazem) alone and associated to non depolarizing (pancuronium) and depolarizing (succinylcholine) neuromuscular blockers, were evaluated on sciatic nerve-tibialis anterior muscle preparations from cats in vivo. The calcium antagonists used (at 0.1 and 0.5 mg/kg iv) did not modify the height of muscular twitches elicited indirectly. However, these agents potentiated in a dose-dependent way the neuromuscular blockade induced by iv pancuronium (2-40 micrograms/kg) and succinylcholine (6-200 micrograms/kg). The order of potency in increasing the effects of pancuronium was nicardipine much greater than d-cis diltiazem greater than or equal to verapamil, whereas the order of potency in enhancing succinylcholine effects was d-cis diltiazem greater than or equal to verapamil much greater than nicardipine. The effects of diltiazem were stereoselective, thus the potentiation induced by d-cis diltiazem was significantly greater in all cases than that induced by l-cis diltiazem, which suggests that calcium channel blockade plays a role in these interactions. However, other mechanisms such as calcium antagonists-induced nicotinic receptor desensitization may also be involved. PMID- 1418859 TI - Effects of 3,N,N'-trimethyl-2-phenyl-1,4-piperazine diastereomers on monoamine uptake and monoamine oxidase in rat brain. AB - The diastereomers of 3,N,N'-trimethyl-2-phenyl-1,4-piperazine dihydrochloride (TPP) were tested for their effects on NA, DA and 5-HT uptake in synaptosomes prepared from hypothalamus, corpus striatum, and frontal cortex, respectively. The diastereomers differed with respect to their inhibitory properties. (2 R, 3 R)-TPP was more potent than the other diastereomers on NA and DA uptake, whereas (2 S, 3 S)-TPP was least potent. In contrast, the (2 S, 3 S)- and (2 S, 3 R) diastereomers of TPP were more potent than (2 R, 3 R)- and (2 R, 3 S)-TPP as inhibitors of 5-HT uptake. None of the diastereomers affected monoamine oxidase activity. The findings show that the diastereomers of TPP interact stereoselectively with neuronal mechanisms for monoamine uptake, and that the (S) configuration at the 2 carbon is important for inhibitory actions of TPP on 5-HT uptake. PMID- 1418862 TI - Increased binding of 3H-L-deprenyl in spinal cords from patients with amyotrophic lateral sclerosis as demonstrated by autoradiography. AB - The present investigation has applied quantitative autoradiography and histochemistry to study the regional distribution of MAO-B and its relation to the number of cells in respective regions. L-deprenyl binds irreversibly and quantitatively to the B-form of monoamine oxidase, MAO, and is an ideal 3H-ligand to measure the MAO-B enzyme protein in tissues by means of in vitro autoradiography. The investigation is performed on spinal sections from five controls and five cases with amyotrophic lateral sclerosis (ALS) on cervical, thoracic and lumbar level. The highest density of 3H-L-deprenyl binding was found around the central canal (lamina X). MAO-B was markedly increased (up to 2.5 times of values in controls) specifically in regions of neurodegeneration e.g. motor neuron laminae and corticospinal tracts. There was a high correlation between glial cell count and 3H-L-deprenyl binding with a relation indicating enhanced MAO-B protein in glial cells within areas of neurodegeneration. In contrast the increased microglial cell number in ALS did not show any correlation with 3H-L-deprenyl binding. PMID- 1418861 TI - Disappearance of hypothalamic TRH asymmetry in suicide patients. AB - The aim of the present study was to investigate the functional and/or pathological significance of the hemispherical lateralization of TRH using radioimmunoassay to determine the TRH concentration of nuclei and areas within the hypothalamus of suicide patients, with matching measurement being carried out on control subjects. In suicide patients, we found no significant difference in TRH concentration between the left and right intrahypothalamic structures, while the group used as control subjects (see Borson-Chazot, 1986) showed a significant left side predominance in the ventromedial nucleus, paraventricular nucleus and area dorsalis. As regards the TRH concentration in the right intrahypothalamic structures, no significant difference was found between the suicide patients and the control subjects. The absence of the left TRH predominance for the three intra-hypothalamic structures in question may be of pathological significance. PMID- 1418863 TI - The effects of deprenyl on methamphetamine-induced dopamine depletions. AB - The effects of deprenyl on methamphetamine-induced dopamine depletions were studied in mice. Four SC injections of 12.5 mg/kg of methamphetamine at two-hour intervals caused substantial (72-82%) and long-lasting depletions of striatal dopamine. Pretreatment with either 25 or 40 mg/kg of deprenyl did not significantly alter the magnitude of this depletion. These results indicate that, unlike what is observed following MPTP, there is no protection afforded dopaminergic cells by deprenyl pretreatment in the methamphetamine model of parkinsonism. PMID- 1418864 TI - Effect of the selective MAO-A inhibitors brofaromine, clorgyline and moclobemide on human platelet MAO-B activity. AB - MAO-B activity was compared in healthy volunteers following oral treatment with clinically effective doses of the selective MAO-A inhibitors brofaromine (100 mg q.d. for 14 days), moclobemide (150 mg t.i.d. for 14 days) and clorgyline (5 mg t.i.d. for 10 days). Brofaromine and clorgyline did not alter platelet MAO activity. Following moclobemide treatment, MAO-B activity was reduced by 32% (p less than 0.05). It recovered during the 5 subsequent days after discontinuation of treatment. These results confirm earlier findings. The explanation for this finding may be that metabolites of moclobemide are active inhibitors of MAO-B. PMID- 1418865 TI - Effect of serum on adrenal PNMT activity. AB - Humoral mechanism should be responsible for activation of PNMT (phenylethanolamine N-methyltransferase) by CRF (corticotropin-releasing factor) in vivo (Lima and Sourkes, 1987). Small amounts of serum (10 microliters) caused a sig. dose dependent activation of bovine PNMT activity (19.0 +/- 1.8%) changing in Km and Vmax values in vitro. Human/rat or ovine CRF--in high amounts (8.4 nmol) only--increase at the rate of just 10% bovine PNMT activity in vitro. At the moment, we do not know which factor in serum is responsible for the increase in A (adrenalin) synthesis in vitro. PMID- 1418866 TI - Anticonvulsant activity of carbamazepine and diphenylhydantoin against maximal electroshock in mice chronically treated with aminophylline. AB - The anticonvulsant activities of both carbamazepine and diphenylhydantoin alone (after a single intraperitoneal administration) or combined with aminophylline were studied against maximal electroshock-induced convulsions in male mice. Aminophylline (injected acutely at 50 mg/kg) significantly increased the ED50 values of both antiepileptics. Given for three days, aminophylline (50 mg/kg, twice daily) still impaired the potency of both antiepileptics and after chronic aminophylline administration a further decrease in the protective activity of carbamazepine and diphenylhydantoin was found. Specifically, after 14 days of aminophylline treatment, ED50s for carbamazepine and diphenylhydantoin were 26 and 19 mg/kg, respectively. These ED50s were significantly elevated compared to values determined after acute aminophylline treatment (21.2 and 14.9 mg/kg, respectively). Plasma levels of both antiepileptics were unaffected by chronic aminophylline which seems to exclude a pharmacokinetic interaction in terms of total plasma levels at least. The present results clearly indicate that the aminophylline-induced impairment of the anticonvulsant activity of carbamazepine and diphenylhydantoin is enhanced over time. This may render aminophylline a hazardous drug to epileptic patients who are prescribed this smooth muscle relaxant. PMID- 1418867 TI - Antagonism by 8-OH-DPAT, but not ritanserin, of catalepsy induced by SCH 23390 in the rat. AB - In the present experiments, it was shown that the catalepsy induced by the dopamine D1 antagonist SCH 23390 (0.2 mg kg-1 sc), was completely antagonised by the administration of 8-OH-DPAT (0.1 mg kg-1 sc) for the duration of the effect of SCH 23390 (approx. 120 min). Neither the catalepsy induced by raclopride (16 mg kg-1 sc) nor that induced by SCH 23390 (0.2 mg kg-1 sc) could be antagonised by treatment with the 5-HT2 receptor antagonist ritanserin (0.13-2.0 mg kg-1 sc). Administration of SCH 23390 (0.0125-0.2 mg kg-1 sc) produced a significant suppression of avoidance behavior at all doses, and also produced a significant decrease in the number of intertrial crosses. At the higher doses, 0.05 and 0.2 mg kg-1 sc, there were also escape failures. In contrast to the finding in our previous report that raclopride and 8-OH-DPAT in a synergistic manner produce a suppression of conditioned avoidance behavior, no such interaction was found between 8-OH-DPAT (0.1 mg kg-1 sc) and SCH 23390 (6 micrograms kg-1 sc) in the present study. PMID- 1418868 TI - Decrease in mesencephalic dopamine autoreceptors in experimental herpes simplex encephalitis. AB - Brain dopamine receptors were determined in experimental herpes encephalitis using an animal model, where herpes simplex virus type 1 was inoculated onto the cornea of rabbits. The animals exhibit an asymmetric posture and circling to the side of inoculation, which appears to be connected to the altered dopamine transmission in the mesostriatal system. In this study striatal and mesencephalic D-1 and D-2 dopamine receptors were measured by radioligand techniques using 3H SCH 23390 and 3H-spiroperidol as ligands. In the striatal D-1 and D-2 receptors there were no significant differences between HSV-inoculated and control rabbits. In the substantia nigra-ventral tegmental area there was a significant decrease in the D-2 receptors (Bmax) on the side contralateral to the primary virus inoculation and the direction of the rotational behaviour, without any changes in the D-1 receptors. Thus experimental herpes simplex virus infection seems to affect the mesencephalic dopamine autoreceptors, leading to unilateral activation of the mesostriatal dopamine system and rotational behaviour. PMID- 1418869 TI - Morphometric and neurosecretory changes in supraoptic neurons after D-amphetamine treatment. AB - Several morphological and immunochemical characteristics of the neurosecretory neurons of the supraoptic nucleus (SON) have been studied of rats treated for 1 month with D-amphetamine sulfate (AMP) (8 mg/kg weight, daily). An increase of SON volume (11%) has been observed as a consequence of the growth of the dorsoventral axis. Neurosecretory neurons increased their nucleolar area (11.4%), their nuclear area (8.3%), and their cytoplasmatic area (18.3%). Vasopressin immunoreaction did not show any differences between treated and control animals, but oxytocin immunostaining displayed an important increase (23.7%) in the neuronal cytoplasm of the treated rats. The SON hypertrophy of the AMP-treated rats corresponded to the hypertrophy/hyperfunction of its oxytocinergic neurons, and could be considered as a new mechanism of the action of the AMP. The results are discussed in relation to the plastic features of the SON and its central (neuronal) and peripheral (hormonal) function. PMID- 1418870 TI - [Tl-201 myocardial scintigraphic findings in patients with aortic regurgitation]. AB - To evaluate the myocardial damage associated with aortic regurgitation, thallium 201 myocardial scintigraphy was performed in 13 patients with aortic regurgitation. The data obtained by thallium-201 single photon emission computed tomography were expressed as the extent score, and were compared with data by echocardiography. The results were as follows: 1. In 11 of 13 patients, there were moderate Tl defects in the distribution of bull's eye map, 80% in the apex, 50% in the inferior and lateral regions, 30% in the anterior region and 10% in the septal region. The mean extent score was 22.3 +/- 11.0%. 2. The extent score correlated with the increase in aortic regurgitant flow volume. The extent score according to the Sellers' classifications II, III, and IV was 13.8 +/- 3.7%, 20.1 +/- 9.8% and 31.9 +/- 10.2%, respectively. 3. There was a good negative correlation between the extent score and fractional shortening (r = -0.66, p < 0.01), however, no significant correlation was observed between the extent score and the left ventricular end-diastolic volume. These results suggest that Tl defects in patients with aortic regurgitation are mainly due to myocardial ischemia associated with a decrease in coronary perfusion pressure and that the extent score may sensitively reflect the severity of myocardial damage in cases with aortic regurgitation. PMID- 1418871 TI - [Clinical significance of the click intervals for the diagnosis of dysfunction of the Medtronic-Hall prosthetic valve]. AB - To investigate the clinical significance of click interval for evaluation of prosthetic valve dysfunction, 20 patients underwent Medtronic-Hall (MH) valve replacement (14 in the mitral position and 6 in the aortic position) were studied by simultaneous high-speed recordings of phonocardiogram, echocardiogram and/or Doppler echocardiogram. Two of the 20 patients, one in the mitral and the other in the aortic position, showed MH valve dysfunction. Eleven patients with normally functioning Bjork-Shiley (BS) valve in the mitral position served as controls. Results were as follows: 1. There were usually 3 opening clicks (OC1, OC2, OC3) in patients with normally functioning MH valve in the mitral position. These 3 clicks coincided in timing with the beginning of opening, maximum opening and the end of sliding motion, respectively. Both OC1 and OC2 of the MH valve occurred in similar timing with those of the BS valve (A2-OC1 interval: MH = 65.4 +/- 11.8 msec vs BS = 72.3 +/- 17.2 msec; OC1-OC2 interval: MH = 31.2 +/- 7.7 msec vs BS = 27.3 +/- 6.1 msec). However, OC3 occurred significantly later in MH valve than in the BS valve (OC2-OC3 interval: MH = 32.3 +/- 7.5 msec vs BS = 16.4 +/- 3.8 msec, p < 0.01). 2. There were 2 closing clicks (CC1, CC2) in normally functioning the MH valve in the aortic position. These 2 clicks coincided in timing with the beginning and the end of the closing motion, respectively. Mean value of CC1-CC2 interval in 5 prosthetic patients with normal function was 31.0 +/- 9.6 msec. 3. A patient with malfunctioning MH valve in the mitral position showed a markedly prolonged OC1-OC2 interval, ranging from 66 to 140 msec, and she had multiple diastolic clicks after the OC2 phase. Prolonged OC1-OC2 interval was mainly caused by the delay of appearance of OC2, and it was thought to be due to temporary limitation of opening motion of the valve by valve thrombosis. 4. A patient with malfunctioning MH valve in the aortic position showed a markedly prolonged CC1-CC2 interval (100 msec), and he had a significant severe aortic regurgitation during this phase. At operation, fibrinoid thrombus was attached to the aortic annulus at the side of minor orifice of the valve. Closing motion of the valve was disturbed by this thrombus, and the completion of valve closure was markedly delayed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1418872 TI - [Congenital bicuspid aortic valve: stenotic type and insufficient type]. AB - Two-hundred and eighty-one patients underwent surgical treatment of the aortic valves during a 10-year period of 1981 to 1991, 32 of whom (11%) had bicuspid aortic valve. Bicuspid aortic valve is well known to cause calcified aortic stenosis, however, some of these cases develop pure aortic insufficiency of unknown etiology. In our studies of 32 patients with bicuspid aortic valve, 28 patients had aortic stenosis, 2 were aortic insufficiency and 2 were infective endocarditis. Pathogenesis of aortic insufficiency in patients with bicuspid aortic valves was discussed and compared with that of aortic stenosis. PMID- 1418873 TI - [Prosthetic valve function evaluated by ultrafast computed tomography (Imatron C 100)]. AB - Ultrafast computed tomography (UFCT) is a new diagnostic modality that includes not only imaging of cardiac structures, but also movement of cardiac muscles and valves. It can be useful in the evaluation of prosthetic valves, because the scan time is extremely short and whole cardiac structures are imaged with a slice thickness of 8 mm and within 7 cardiac cycles. We review our experience using UFCT to observe prosthetic valve function in 22 cases with various valvular diseases. PMID- 1418874 TI - [A family of Marchesani syndrome with mitral valve prolapse and anuloaortic ectasia]. AB - Marchesani syndrome consists of short statue, small spherical lens, glaucoma and brachydactyly, which are manifestations of hyperplastic connective tissue disease in systemic organs of mesodermal origin (Marchesani 1939). Among nearly 200 cases of Marchesani syndrome reported in the ophthalmology field, none has shown cardiac manifestations which typically characterize Marfan syndrome caused by hypoplastic connective tissue disorders. We experienced 2 cases which met the diagnosis of Marchesani syndrome and yet showed annuloaortic ectasia and mitral valve prolapse. A 30-year-old man and a 26-year-old woman who are siblings suffered from manifested brachydactyly, spherophakia, glaucoma and cardiac involvements. Their parents are in consanguinity. These unprecedented cases with mixed manifestations provide the evidence of possible gene-crossing between these 2 dystrophic mesodermal disorders. PMID- 1418875 TI - [Vagal innervation in the human atrioventricular valves]. AB - Innervation of the human atrioventricular (AV) valves is microscopically studied by histopathological methods. The tricuspid and mitral valves of 4 autopsied hearts of adult men (age range from 50 to 74 years old) without any cardiovascular diseases were stained for acetylcholine-esterase by histochemical method in the medium containing acetylthiocholine iodide. Acetylcholine-esterase positive nerve fibers of 2 to 50 microns in diameter were widely distributed in the subepicardial space of the atrial of the AV valve. They formed a coarse network of the nerve elements from the valve base to the anatomical edge. The nerve network was more dense at the valve ring and base, as well as at the commissure, than at the edge and body. Some thick nerve fibers ran in the chordae tendineae. The thick fibers were intercalated with varicose-like special structures at several places in the leaflets, which seemed to be a kind of sensory apparatus. The thin nerve fibers ended, as usual, at small dot or brush like apparatus. It is widely accepted that the acetylcholine-esterase positive nerve fibers are identical with vagal nerves which are insisted on participating in development of mitral valve prolapse syndrome. We suggest that the vagal innervation in the AV valves could play an important role for valvular function. PMID- 1418876 TI - [Mitral valve prolapse associated with partial absence of commissural chordal insertion: report of two cases]. AB - We reported 2 cases of mitral valve prolapse (MVP) associated with partial absence of the chordae tendineae. Case 1 was a 25-year-old man who was admitted to our hospital for further examinations of an apical pansystolic murmur (Levine 4/6) and the abnormal shadow on his chest radiograph. He was diagnosed as having grade 3 + mitral regurgitation (MR) by the Sellers classification and pulmonary varix by cardiac catheterization. Transesophageal echocardiography revealed MVP of the rough zone of the anterior mitral leaflet and MR blowing into the pulmonary varix. Case 2 was a 60-year-old man who was admitted to our hospital because of congestive heart failure and apical pansystolic murmur (Levine 4/6). Parasternal echocardiography revealed prolapse of both the anterior and posterior mitral leaflets and moderate MR. In both cases, absence of insertion of anterolateral commissural chordae was confirmed after surgery, and the abnormalities of chordal arrangement and insertion were considered as causes of MVP in these cases. PMID- 1418877 TI - Valvular disease of the heart in the elderly. PMID- 1418878 TI - [Evaluation of left ventricular relaxation by mitral regurgitant curve]. AB - To examine whether left ventricular (LV) isovolumic relaxation can be assessed noninvasively using a continuous-wave Doppler technique, we compared Doppler determined parameters derived from mitral regurgitation (MR) velocity curve with micromanometer-derived indices of LV relaxation, peak negative dP/dt and tau, in 9 patients with MR (5 with dilated cardiomyopathy, 2 with old myocardial infarction and 2 with rheumatic MR). The rate of LV pressure decay (delta P/delta t) at aortic valve closure was calculated from the recordings of MR jet velocities based on the simplified Bernoulli equation. The time constant of LV pressure decay (tD) was determined as the time from the aortic valve closure to the point where the velocity declined by (1/e)1/2. Doppler-determined delta P/delta t correlated well with hemodynamic peak negative dP/dt (r = 0.97, p < 0.001), and tD with hemodynamic tau (r = 0.89, p < 0.005). Thus, we concluded that left ventricular isovolumic relaxation can be noninvasively assessed with a continuous-wave Doppler technique in the presence of mitral regurgitation. PMID- 1418879 TI - [A clinicopathologic study of morphologic tricuspid valve prolapse in the aged: comparison with color Doppler evaluation]. AB - Similar morphologic abnormalities have often been observed in the leaflets of tricuspid valve in patients with mitral valve prolapse. In the present study, morphologic tricuspid valve prolapse was analyzed in 500 consecutive autopsies of the aged over 60 years (mean 78.5 yrs, 266 men, 234 women). Additionally, the sensitivity and specificity of the color Doppler technique applied before death were assessed in 61 autopsy cases. The results were as follows: 1. The incidence of morphologic tricuspid valve prolapse was 22.2% at autopsy in 500 cases of the aged, however, tricuspid regurgitation had not clinically been detected in any of them. 2. The prolapse of 2- or 3-leaflets was common (78.5%). Among the 3 leaflets, the prolapse was more frequently observed in the anterior or posterior leaflet than in the septal leaflet. Combined tricuspid and mitral valve prolapses were observed in 22 cases (19.8%). 3. Among 61 cases examined by color Doppler echocardiography, autopsy showed that 16 cases had tricuspid valve prolapse and 14 cases tricuspid regurgitant flow signals (87.5%). 4. Regurgitant flow signals were also detected in 4 of 12 morphologically normal cases (33.3%). 5. In autopsy cases of the aged, generally, the incidence of morphologic tricuspid valve prolapse and tricuspid regurgitant flow signal were high, however, hemodynamically significant regurgitation due to prolapse was very rare. PMID- 1418880 TI - [A case of cardiac lipoma of the anterior tricuspid leaflet]. AB - A 42-year-old man with cardiac lipoma of the anterior tricuspid leaflet is reported. He had a chief complaint of epigastric discomfort, and a pansystolic murmur was heard at the left sternal border in the 4th intercostal space. Two dimensional echocardiography disclosed a mobile high density stalkless mass having several areas of low density. Two-dimensional Doppler echocardiogram revealed a moderate degree of tricuspid regurgitation. These findings were more clearly visualized on transesophageal echocardiogram. MRI revealed a high signal intensity on the T1-weighted image and a high radiodensity surrounding the mass using a contrast medium of Gd-DTPA. A 2.0 x 1.3 x 0.8 cm hemispherical, lobulated and sessile yellow mass was excised by means of open heart surgery, and tricuspid valvuloplasty was performed. The mass was adipose tissue and was surrounded by fibrous tissue just under the lamina fibrosa. These findings were compatible with those of the preoperative examinations, although the preoperative diagnosis was not conclusive. This was our first case of cardiac lipoma in which the tricuspid valve was successfully excised. PMID- 1418881 TI - [Long-term effect of medical treatment in patients with chronic aortic regurgitation]. AB - We often experience patients with chronic severe aortic regurgitation (AR) whose cardiac function significantly improves by medications, especially by vasodilator therapy. To find the factors determining the response to pharmacologic treatment, we studied 20 patients with chronic AR with dilated left ventricle (end-diastolic dimension > or = 55 mm) using echocardiography; 9 patients with significant improvement (delta Ds < or = -3 mm: improved group) and 11 without improvement (unchanged group). In the initial evaluation, systolic blood pressure and left ventricular relative wall thickness (Thd/Dd) were greater and left ventricular end-diastolic dimension was smaller in the improved group than in the unchanged group. During the follow-up period, systolic blood pressure and end-systolic wall stress decreased significantly and absolute and relative wall thickness increased significantly in the improved group, however, they remained nearly the same in the unchanged group. Significant negative correlation was observed between Thd/Dd and delta Ds. In conclusion, cardiac function in some patients with chronic AR can be improved by pharmacologic treatment, and in such cases, the Thd/Dd ratio could be a parameter of the response to pharmacologic treatment. PMID- 1418882 TI - [Doppler and echocardiographic study of normal systolic murmurs]. AB - To elucidate the genesis of normal ejection systolic murmurs, we performed phono and Doppler echocardiography in 42 normal subjects. Individuals with hypertension, ST.T changes on ECG, anemia or other cases with definite cardiovascular findings were excluded from the study. Their ages ranged from 22 to 61 years with an average of 48.1 years. They were classified in 2 groups; 9 with Levine 2/6 systolic murmur and 33 without murmur or with 1/6 murmur. Fifteen patients with pure aortic regurgitation or with aortic prosthesis but without significant stenosis, and 7 patients with pulmonic valvular stenosis were served as control. We correlated the intensity and timing of murmur with maximal flow velocity, acceleration time and other parameters. All systolic murmurs were early systolic. Mid-systolic murmur was not noted. Peak of flow velocity increased at the aortic orifice than at the left ventricular outflow tract or pulmonary orifice. Left-sided peak flow velocity occurred earlier than the right-sided peak flow velocity. Early systolic maximal flow velocity of the aorta significantly increased in 9 subjects with murmur than in the remaining 33 without significant murmur. Ejection fraction, hematocrit and body surface area did not differ between the groups with and without significant murmur. Systolic blood pressure and age, however, were higher in subjects with murmur. In aortic valvular disease, systolic murmurs and peak flow signals were early systolic, but in pulmonary stenosis these were mid-systolic in timing. In conclusion, normal ejection systolic murmurs were early systolic and originated at the aortic orifice. Mid-systolic murmurs were unlikely as left-sided murmur in origin. Flow velocity was the most important determinant of the intensity of ejection murmur. PMID- 1418883 TI - [Evaluation of aortic regurgitation by Doppler echocardiography]. AB - To establish a method for evaluating aortic regurgitation (AR) using Doppler echocardiography, we studied 104 patients who were classified according to aortographic grading (Sellers). The severity of the AR was graded by measuring the length of AR jet within the left ventricle by pulsed Doppler mapping (mapping method) or by two-dimensional color Doppler echocardiography (length method). Also, color Doppler echocardiography was used to measure the width of AR jet just below the aortic valve (width method), and pulsed Doppler echocardiography to determine the fraction of integral of forward flow and reverse flow in the abdominal aorta (abdominal method). Although the diagnostic accuracy of grading by these Doppler techniques only ranged between 52% and 68%, the length method combined with the abdominal one enhanced the diagnostic accuracy to 89% in retrospective study and 80% in prospective study. In conclusion, the length method combined with the abdominal method appeared to be useful and reliable in evaluating AR. PMID- 1418884 TI - Do central antiadrenergic actions contribute to the atypical properties of clozapine? AB - Full neuropharmacological understanding of the atypical antipsychotic agent clozapine remains elusive. Antidopaminergic actions of most neuroleptics probably contribute to their antipsychotic benefits, but also to neurological side effects. Clinical evidence of abnormalities of dopamine (DA) and serotonin (5-HT) in psychotic disorders is inconsistent, but there is substantial metabolic and post-mortem evidence for hyperactivity of noradrenaline (NA). Clozapine is only weakly antidopaminergic but is a potent antagonist at brain alpha 1-adrenergic, 5 HT2-serotonergic, and muscarinic receptors. Its apparent limbic-over extrapyramidal neurophysiological selectivity can be mimicked by combining a typical neuroleptic with a central alpha 1 antagonist. Clozapine strongly upregulates alpha 1, but not DA, receptor abundance, and may supersensitise alpha 1 but not DA receptors in rat brain. Clozapine also selectively increases activity of NA neurons and metabolic turnover in NA more than DA areas of rat brain, and also increases NA, but not DA or 5-HT, metabolites in human CSF. Potential psychotropic effects of selective central antiadrenergic agents may deserve reconsideration. PMID- 1418885 TI - Clozapine: a hypothesised mechanism for its unique clinical profile. AB - Clozapine's clinical profile is unique among antipsychotic drugs. What makes it different? For almost two decades researchers have been attempting to answer this question. Based on various data, many hypotheses have been proposed. Using electrophysiological techniques we have found that clozapine, like typical antipsychotic drugs, inactivates most midbrain dopamine cells secondary to the induction of depolarisation block. However, unlike classical antipsychotic drugs, clozapine does not inactivate the nigrostriatal dopamine system. Based on these and other findings the hypothesis of 'depolarisation block' is reviewed and presented as an explanation for clozapine's unique clinical profile. Research data both for and against the hypothesis are then discussed. PMID- 1418886 TI - Clozapine and D1/D2 antagonism in extrapyramidal functions. AB - One of the main advantages of clozapine is that it rarely produces extrapyramidal syndromes and tardive dyskinesia. This advantage is linked to the atypical biochemical profile of clozapine, especially its combined and low blockade of D1 and D2 receptors. The level of D2 receptor blockade is too low to induce extrapyramidal side-effects, and D1 antagonists have a lower extrapyramidal side effect potential than traditional D2 neuroleptics, especially with respect to dystonia. The combined and balanced D1/D2 receptor blockade may prevent the development of a dysbalance between D1/D2 receptor function (in favour of D1) which otherwise might lead to tardive dyskinesia. PMID- 1418887 TI - Clozapine-associated agranulocytosis: risk and aetiology. AB - This paper reviews the epidemiology and pathogenesis of clozapine-associated agranulocytosis. According to present clinical experience, granulocytopenia can be expected in approximately 3% of patients during clozapine treatment. The risk of serious sequelae of granulocytopenia can be minimised by regular white blood cell count monitoring. Although research suggests that some patient groups may be at higher risk of developing this serious adverse reaction, we cannot yet predict the susceptible patients, so all patients exposed to clozapine should receive regular blood monitoring throughout treatment. Because of the risk of agranulocytosis, clozapine should only be used in schizophrenic patients who are resistant to, or intolerant of, conventional antipsychotic medications. Unless compliance with blood monitoring is assured, clozapine treatment should not be recommended. PMID- 1418888 TI - Clinical efficacy of clozapine in treatment-refractory schizophrenia: an overview. AB - The treatment of patients with schizophrenia who fail to respond to antipsychotic medications remains a challenge. Despite numerous attempts to establish effective somatic treatment approaches for this population, clozapine appears to be the only well established alternative. Depending upon trial duration and response criteria, between 30% and 60% of previously unresponsive patients appear to derive clinically significant benefit from clozapine. Clozapine also has important advantages in terms of its reduced propensity to produce extrapyramidal side-effects. Agranulocytosis remains an important risk, so strategies to improve the benefit-to-risk ratio should be explored. Issues such as trial duration, dosage, blood levels and predictors of response require additional study. PMID- 1418889 TI - Dimensions of outcome with clozapine. AB - Various outcome measures following clozapine administration to neuroleptic resistant schizophrenic patients are considered. The importance of a multidimensional perspective is emphasised. There was significant improvement in positive symptoms, some negative symptoms, quality of life, some types of cognitive function (e.g. semantic memory), extrapyramidal function, and tardive dyskinesia. Readmission to hospital, and family burden were markedly reduced, which achieved significant savings in the cost of treatment. Compliance with clozapine and weekly blood testing can be achieved in the majority of treatment resistant cases. These benefits may occur independently of each other. PMID- 1418890 TI - Activity and tolerability of tetridamine vaginal lavage in rats and women. AB - Tetridamine (2-methyl-3-methylamino-4,5,6,7-tetrahydroindazole) is a well known analgesic and anti-inflammatory drug. Here the activity and the tolerability of a new 0.134% tetridamine formulation in rats and women, are reported. Anti inflammatory and analgesic tests were performed in Sprague-Dawley rats with carrageenin oedema; topical application of 0.134% tetridamine solution showed a marked reduction of paw swelling (-54.4%) and pain sensibility (-81.0%). A 28 days vaginal tolerability study performed on Sprague-Dawley rats with tetridamine lavage (0.2 ml/rat/day) showed, in comparison with control group, no changes in haematology, coagulation, clinical biochemistry and in histological examinations of uterus and vagina. Clinical studies (4 open and 1 double-blind) were performed on 93 women suffering from vulvovaginitis and cervicitis by treatment of 0.134% tetridamine vaginal lavage, two times daily, for 7 days. Tetridamine lavage reduced or eliminated all inflammation symptoms like burning, leucorrhea, etc. and resulted very well tolerated. From these pharmacotoxicological and clinical results we can conclude that tetridamine vaginal lavage is a new formulation with high activity and good tolerability. PMID- 1418891 TI - [Intranasal absorption of various calcitonin spray preparations]. AB - In a cross-over study performed on 10 patients the intranasal absorption of calcitonin contained in three formulation spray was evaluated. One of them contained biliary acid (sodium taurocholate) as the absorption promoting factor while the other two drugs did not. The dosage of calcitonin in blood was effected by means of radioimmunoassay using salmon calcitonin marked with I126 in competition to the one present in the sample for a limited quantity of specific antibodies for salmon calcitonin. The minimum measurable quantity of calcitonin is 10 pg and the response is linear including values between 20% and 80%. It is observed that the plasmatic concentration of calcitonin dosed in different times after administration of the drug containing sodium taurocholate are always significantly higher (Student "t" test for unpaired data, p less than 0.005) than the measurements after administration of the other two drugs. They are about 8 times higher at the first half an hour, about 6 times after an hour and again double at the second hour. The AUC calculated for sodium taurocholate containing drug (1629 pg/ml/h) results significantly higher in relation to the other two drugs (1133 and 926 pg/ml/h) indicating a better bio-availability of calcitonin contained in that spray. The relative bioavailability between calcitonin spray with sodium taurocholate and the other two drugs in reference resulted to 144% and 176%. The presence of a transmucosal absorption promoting factor at the level of a nasal mucosa, represented in this case by sodium taurocholate, enhances significantly the absorption and the bioavailability of calcitonin present in the formulation spray. PMID- 1418892 TI - Extracapsular spread and the perineural extension of squamous cell cancer in the cervical plexus. AB - Extracapsular spread of squamous cell carcinoma in cervical lymph nodes is associated with approximately 50% decrease in survival and a twofold increase in regional recurrence. This study examines the hypothesis that increased regional recurrence may be, in part, due to unrecognized microscopic perineural invasion of the nerve rootlets of the cervical plexus. Thirty patients with head and neck squamous cell carcinoma with clinically N+ necks undergoing radical neck dissection were prospectively studied. Neck dissection specimens were evaluated for extracapsular spread, and the cervical plexus rootlets were histologically examined for perineural invasion. The incidence of extracapsular spread was 83% (25 of 30 patients). Only one (4%) of 25 had involvement of the cervical plexus, and this patient had gross as well as microscopic cervical plexus invasion. Microscopic perineural spread of squamous cell carcinoma in the cervical plexus occurs infrequently when extracapsular spread is present. Routine histologic evaluation of cervical rootlets for margins is warranted only when gross tumor is in close proximity to the cervical plexus. PMID- 1418893 TI - Ampicillin-sulbactam vs clindamycin in head and neck oncologic surgery. The need for gram-negative coverage. AB - This study was undertaken to assess whether gram-negative antimicrobial coverage is required in patients undergoing head and neck oncologic surgery. Ampicillin sodium-sulbactam sodium and clindamycin phosphate were compared in a prospective, randomized, parallel, double-blind trial of 212 patients undergoing head and neck procedures involving clean-contaminated wounds. Both antibiotics were given up to 1 hour before surgery and continued at 6-hour intervals after surgery for an additional eight doses. Fourteen infections occurred in the ampicillin-sulbactam treated group (13.3%) and 29 infections in the clindamycin-treated group (27.1%). From patients receiving clindamycin, 29 gram-negative organisms were isolated, compared with six from those patients receiving ampicillin-sulbactam. This finding supports the need for gram-negative coverage in patients undergoing clean contaminated head and neck oncologic surgery. PMID- 1418894 TI - Transmandibular approaches to the oral cavity and oropharynx. A functional assessment. AB - The records of patients undergoing transmandibular approaches to soft-tissue carcinoma of the oral cavity and oropharynx were reviewed retrospectively. Thirty nine patients requiring lateral segmental hemimandibulectomy and 45 patients requiring a mandibulotomy were identified. None of the patients given mandibulectomy underwent bone reconstruction, while all of the patients with mandibulotomy had repair at the completion of the case. A total of 53 patients were available for recall and functional assessment. Patients with mandibulotomy did not experience significant dysfunction of the temporomandibular joint. Patients with mandibulectomy demonstrated increasing amounts of eccentric occlusion; however, this did not affect diet and was not reported to be uncomfortable by these patients. When feasible, preservation of the mandible yielded an improved aesthetic result; however, functional results in patients requiring mandibulectomy compare favorably with those obtained after mandibulotomy and repair. PMID- 1418895 TI - Tumor necrosis factor and chemotherapeutic agents. Potentiation of cytotoxicity with interferon gamma. AB - This study examined combinations of the recombinant human cytokines, tumor necrosis factor alpha and interferon gamma, with doxorubicin and dactinomycin as well as other drugs on six squamous cell carcinoma cell lines of head and neck origin using the 3(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide proliferation assay. Interferon gamma significantly enhanced the cytotoxicity of tumor necrosis factor alpha with dactinomycin on all six cell lines investigated, while in four of six cell lines the cytotoxicity of tumor necrosis factor alpha with doxorubicin was significantly augmented by interferon gamma. Additional experiments showed no effect with either cytokine in combination with cisplatin, fluorouracil, methotrexate, or etoposide. These data demonstrate that human recombinant cytokines in concert with certain drugs improve in vitro cytotoxicity and may have a potential for improving in vivo therapy. PMID- 1418896 TI - A study of the heterogeneity of the mucoepidermoid tumor and the implication for future therapies. AB - Mucoepidermoid carcinomas are common head and neck neoplasms whose wide distribution includes the major salivary glands, especially parotid, the minor salivary glands within the oropharynx, sites within the larynx, and the submucosal bronchial glands. These tumors are heterogeneous neoplasms composed of intermediate, squamous, and mucous cell subpopulations and have been traditionally classified as low or high grade based on their histological nature and tendency for invasion and metastasis. To gain a better understanding of the heterogeneity of these tumors, we conducted in-depth studies of the different cellular subpopulations obtained from primary human mucoepidermoid carcinomas from various sites, and a derived cell line grown in monolayer culture and as a nude mouse xenograft. Flow cytometric and clonal dilution studies indicate that the intermediate cell behaves as a reserve cell capable of differentiating into either the squamous cell or mucous cell. Immunocytochemical studies of bromodeoxyuridine uptake and Ki-67 antigen expression indicate that whereas the squamous and mucous cells are terminally differentiated and permanently arrested in G0, the intermediate cell actively enters G1 and S. Studies of invasion utilizing a human amnionic membrane indicate that only the intermediate cell is capable of active invasion. Because the mucous and squamous cells are incapable of further division or invasion, therapeutic strategies aimed at differentiating the intermediate cell in vivo into either mucous or squamous directions would serve as useful adjuncts to surgery by reducing the rate of recurrence and the incidence of metastasis. PMID- 1418897 TI - Lacrimal drainage system injury in functional endoscopic sinus surgery. Incidence, analysis, and prevention. AB - Injury to the lacrimal drainage system with resultant epiphora is a complication of functional endoscopic sinus surgery. A study of 24 patients was conducted to determine the incidence and significance of lacrimal drainage system injuries during functional endoscopic sinus surgery. Intraoperative testing demonstrated seven occult injuries (15%) in 46 endoscopic procedures. Postoperative testing demonstrated diversion of lacrimal drainage into the middle meatus in two patients and spontaneous healing of the injured lacrimal drainage system with restoration of normal drainage in three of the patients available for follow-up testing. In no patient did epiphora develop. It is concluded that the nasolacrimal drainage system is in close proximity to the dissection cavity during functional endoscopic sinus surgery and, hence, is at risk for inadvertent injury. Occult damage to the nasolacrimal drainage system would appear to be a common event during functional endoscopic sinus surgery; however, the complication of postoperative epiphora is rare. PMID- 1418898 TI - Relative effects of intraoperative tissue expansion and undermining on wound closing tensions. AB - Intraoperative tissue expansion is advocated as a technique to facilitate closure of soft-tissue wounds with less tension than if they were closed primarily without expansion or, presumably, simple undermining. Few objective studies have been done, however, to validate the technique. We specifically questioned the relative effects of intraoperative tissue expansion and undermining on wound closing tensions in an animal model. Our data showed statistically significant reduction in the force required to close a wound after acute intraoperative tissue expansion when compared with baseline. However, when the degree of undermining achieved by the expander was matched in an equivalent defect, no difference in the resultant wound closing tensions could be discerned between techniques. This study should be viewed as an initial effort to understand the role of intraoperative tissue expansion in reconstructive surgery. PMID- 1418899 TI - Facial paralysis reconstruction with Gore-Tex Soft-Tissue Patch. AB - No procedure perfectly restores a face paralyzed by surgical ablation of the facial nerve. Although dynamic reconstructive procedures are preferred for treating patients with complete facial paralysis, various conditions contraindicate their use, making static suspension of the paralyzed face a reasonable surgical alternative. Expanded polytef soft-tissue patch (polytetrafluoroethylene; Gore-Tex Soft-Tissue Patch, Gore-Tex, W. L. Gore & Assoc Inc., Flagstaff, Ariz) was used to help correct midfacial and perioral asymmetries in 11 patients with complete unilateral facial paralysis. All patients had previous surgical ablation of the facial nerve and were not considered good candidates for dynamic facial reconstruction. Midfacial and perioral asymmetries were improved in all patients using this technique of static soft-tissue suspension. One postoperative infection and two cases of postoperative suture extrusion were observed in the patient population. Other complications associated with the use of Gore-Tex Soft-Tissue Patch for facial suspension were limited to technical factors. PMID- 1418900 TI - Otologic complaints in temporomandibular joint syndrome. AB - Complaints of diminished hearing or reduced speech discrimination frequently accompany temporomandibular dysfunction. There is no consensus as to the mechanism of their occurrence or the alteration of these symptoms with the treatment. We studied 12 subjects with internal derangement of the temporomandibular joint (treated surgically) and nine subjects with myofascial pain disorder (treated medically), and we found no difference between the groups in pretreatment audiometric findings or in their degree of otologic symptoms. Similarly, there were no differences in posttreatment audiometric measures and there were no significant treatment effects. Furthermore, there was no correlation between subjects' complaints of reduced hearing sensitivity or discrimination and audiometric results. The apparently significant reduction in symptoms experienced by some subjects in the absence of audiometric change suggests the operation of unmeasured factors in their response to treatment. PMID- 1418901 TI - A clinical profile of otitis media. AB - An otitis media with effusion algorithm developed by Paradise et al and tested by Cantekin et al has become the basis for many studies of otitis media. However, a two-point scale algorithm (otitis media with effusion-no otitis media with effusion) may be too ambitious (ie, low specificity) and too optimistic (ie, absence of fluid does not necessarily mean normal ear). We propose a four-point profile that characterizes the condition of the middle ear, and we report the validation of the profile against findings at myringotomy. Statistically, a four point scale profile would substantially increase powers of statistical tests, compared with a two-point scale algorithm (in studies of the same size), when used to study changes of the middle-ear condition over time or to compare treatment effects. PMID- 1418902 TI - Bacteremia during tonsillectomy. AB - To determine the risk of bacteremia during tonsillectomy, we cultured blood specimens that were taken from 32 children during surgery and tonsillar swabs that were obtained just before excision, and compared the results with quantitative cultures of the excised tonsillar tissue. Twenty-five children had Haemophilus influenzae within the tonsillar tissue (density range, 10(3) to 10(8) colony-forming units per gram), and seven had Streptococcus pyogenes (density, 10(3) colony-forming units per gram in one case, 10(5) colony-forming units per gram in one case, and 10(6) colony-forming units per gram in five cases). Twelve perioperative blood cultures were positive; H influenzae was found nine times, and Micrococcus species was found one time, and alpha-hemolytic streptococci were found two times. Haemophilus influenzae was always present in the corresponding tonsillar specimens, although there was no apparent relationship between the density of colonization of the tonsillar tissue and a positive blood culture. PMID- 1418903 TI - Nasal mucociliary transport of chronic sinusitis in children. AB - Nasal mucociliary function is one of the most important and indispensable mechanisms of the respiratory tract, providing protection against the atmospheric environment. We previously found mucociliary dysfunction in the noses of adult patients suffering from chronic sinusitis. In this study, using the saccharin method, we determined nasal mucociliary function in normal children and in children with chronic sinusitis. The mean (+/- SD) value of saccharin transit time in the nose was 28.2 +/- 19.9 minutes in patients with chronic sinusitis, this being significantly slower than that in the control group of children. The incidence of abnormally slow nasal mucociliary transport time (> 30 minutes) in patients was significantly higher than in controls of the same age. Mucociliary dysfunction may initiate a vicious cycle of self-mediated inflammation and may be important in recovery from chronic respiratory inflammation. PMID- 1418904 TI - Oronasal reconstruction with local mucoperiosteal and free latissimus dorsi flaps. AB - We describe the use of maxillary sinus mucoperiosteum as a pedicled flap to reconstruct the floor of the nose following resection of cancer involving the palate, buccal mucosa, and mandible. Complete inferior turbinectomy allows access to the roof of the maxillary sinus to harvest the mucoperiosteum as a vascularized flap pedicled under the remaining middle turbinate. A free latissimus dorsi myocutaneous flap suspended from the floor of the orbit and nasal septum is then used to obliterate the maxillary sinus, reconstruct the palate, and support the floor of the nose. A reconstruction employing this combination of flaps is presented, including postoperative endoscopic intranasal photography and magnetic resonance imaging. Despite the elevated level of the floor of the nose and the absence of the inferior turbinates, rhinomanometry performed 3 months postoperatively demonstrates adequate nasal airflow with normal responses to nasal decongestants. PMID- 1418905 TI - Sebaceous carcinoma of the head and neck. Case report and literature review. AB - Sebaceous carcinoma is uncommon, with fewer than 400 cases reported. Usually, lesions arise in the meibomian glands of the eyelid; however, extraocular lesions within the head and neck have been reported. Regardless of the location, sebaceous malignancies must be considered aggressive neoplasms with a potential for regional and distant metastasis. Diagnosis may be difficult, given the low incidence and inconsistencies in histopathologic classification. Recently, needle aspiration cytologic characteristics have been delineated, with this procedure becoming increasingly useful in establishing the diagnosis. Treatment requires wide surgical excision with removal of involved regional lymph nodes. Opinions are divided regarding the use of postoperative irradiation or chemotherapy. Records of all patients with sebaceous carcinoma of the head and neck treated at UCLA Medical Center, Los Angeles, over the last 35 years were reviewed. The clinical and pathologic features are discussed, and the literature is summarized. PMID- 1418906 TI - The utility of magnetic resonance imaging in the diagnosis of intranasal meningoencephaloceles. AB - We present three patients in whom the diagnosis of intranasal meningoencephalocele was made by magnetic resonance imaging. The initial clinical evaluation and computed tomographic examinations of these patients failed to distinguish between chronic inflammation and intranasal meningoencephalocele. Although both computed tomography and magnetic resonance imaging are used to distinguish between normal, inflammatory, and neoplastic tissue in the nasal cavity and paranasal sinuses, limitations do exist and these are the focus of our communication. A clear understanding of the efficacy of these radiographic modalities will enhance surgical planning and can preclude severe complications. PMID- 1418907 TI - Histopathology of the temporal bone following multichannel cochlear implantation. AB - The temporal bone histopathologic findings of a patient having received a Nucleus 22-channel cochlear implant (Cochlear Corp, Englewood, Colo) following bilateral transverse otic capsule fractures is presented. The case was complicated by perilymph fistulas, labyrinthitis, meningitis, and death due to drowning. The left cochlea revealed complete labyrinthitis ossificans; the implanted right cochlea demonstrated new bone formation in the basal turn of the scala tympani, degeneration of the organ of Corti, but normal ganglion cell counts. Results of psychophysical and speech perception 4 months after implantation are presented. PMID- 1418908 TI - Pathologic quiz case 2. Myospherulosis of the paranasal sinuses. PMID- 1418909 TI - Pathologic quiz case 1. Ductal cyst. PMID- 1418910 TI - Regulation of erythropoiesis in the newborn: a complex system. PMID- 1418911 TI - Cellular senescence. AB - The ageing of cells, cellular senescence, is an event that is encountered in all normal cells. Cells grown in vitro have a limited life span and do not grow well after a certain number of divisions. They cease to divide and eventually die. In accordance with this, the life expectancy of an established cell culture depends on the age of the donor. Cells that have undergone immortalization via a crisis period of transformation by chemicals or viruses, as well as malignant cell lines in general, have an ability to divide indefinitely. A distinct form of cell death, apoptosis or programmed cell death, is encountered in many physiological situations like in keratinocyte differentiation. PMID- 1418913 TI - Liver transplantation: present results and problems. PMID- 1418912 TI - Progress in the treatment of childhood leukaemias. AB - The Nordic Society for Pediatric Hematology and Oncology (NOPHO) has run a population-based registry on all cases of acute leukaemias in the Nordic countries since 1981. Data on close to 2000 children with these diagnoses are presented and used as a background for a general discussion of progress in the therapy of these challenging conditions. Our material is unique in that it is population based. The results obtained are comparable to those obtained by all other major cooperative groups. Since January 1992, the treatment protocols for all types of acute leukaemias in childhood have been harmonized in the Nordic countries. PMID- 1418914 TI - Leukocyte cell adhesion proteins: from molecular dissection to clinical applications. AB - Leukocyte adhesion is needed for a number of leukocyte functions like immunoglobulin synthesis, T and NK-cell-mediated cytotoxicity, phagocytosis by granulocytes, and cellular accumulation in inflamed tissue. Several cell surface molecules involved in leukocyte-leukocyte and leukocyte-target cell interactions have recently been identified and characterized. Both the polypeptide and carbohydrate portions are important in leukocyte interactions. It is becoming increasingly apparent that it is possible to interfere with the normal functions of the leukocyte adhesion glycoproteins, and such applications may become important in medicine. PMID- 1418915 TI - Toxoplasma pericarditis mimicking systemic lupus erythematosus. Diagnostic and treatment difficulties in one patient. AB - A life-threatening T. gondii pericarditis developed in a patient with symptoms corresponding to systemic lupus erythematosus (SLE) with high concentrations of antinuclear antibodies and lymphadenopathy. The diagnosis would have been SLE associated serositis, had not pericardial fluid been inoculated into mice, because pericarditis is frequently seen in SLE and false positive toxoplasma seroreactions may occur in ANA positive patients. High IgG T. gondii antibodies without increased IgM antibodies indicated reactivation rather than primary infection. Prolonged high-dose treatment with pyrimethamine-sulphadiazine was needed. Interestingly, the patient's SLE symptoms, including high ANA antibodies, declined to an unexpected remission after treatment for toxoplasmosis. This may not be mere coincidence, but may point to a causative role of toxoplasmosis in some cases of SLE. PMID- 1418916 TI - Inhibition of colonic motility by cholecystokinin. AB - Distal colonic motor activity was measured in 12 control subjects and seven constipation-predominant irritable bowel syndrome patients to examine the effects of intravenous administration of cholecystokinin. In the basal state, no significant motility differences were noted between these two groups. Following the intravenous administration of the hormone cholecystokinin, a statistically significant reduction in colonic motility in control subjects and a non significant decrease in motility in irritable bowel syndrome patients was seen. Our results do not suggest an exaggeration of the colonic motor response to cholecystokinin occurs in irritable bowel syndrome. PMID- 1418917 TI - Molecular genetics and genetic epidemiology of cardiovascular diseases and diabetes. Introductory remarks: risk factor levels and variability. PMID- 1418918 TI - Genetic variants of apolipoprotein B: relation to serum lipid levels and coronary artery disease among the Finns. AB - The genetic variation of apolipoprotein B has been studied extensively in Finns with the aid of protein and DNA polymorphisms. Population association studies confirmed significant associations between the XbaI polymorphism of the apolipoprotein B gene and elevated serum cholesterol levels, and dietary studies suggested that the XbaI and ins/del polymorphisms might modify the serum lipid response to dietary fat intake. Studies comparing patients and controls, however, did not confirm previous studies suggesting that the multi-allelic variation at the 3'VNTR region of the apolipoprotein B gene was associated with coronary artery disease. The results suggest that the apolipoprotein B gene is involved in the regulation of serum lipid levels. A yet unknown mutation in linkage disequilibrium with the XbaI site may contribute to this regulation. PMID- 1418919 TI - Molecular genetics of familial hypercholesterolaemia: common and rare mutations of the low density lipoprotein receptor gene. AB - Mutations of the low density lipoprotein (LDL) receptor gene give rise to familial hypercholesterolaemia (FH), one of the most common single-gene diseases in the world. Approximately 150 different LDL receptor gene mutations have been reported until now and the list seems to be continuously growing. Although hampering molecular genetic diagnosis of FH, this wide variability at the DNA level provides a useful tool to population genetics and may ultimately lead to better understanding of the variation in disease manifestations from family to family. The Finns are among the few populations in which one or two mutant LDL receptor genes explain the majority of FH cases. Either of the two 'Finnish-type' LDL receptor gene deletions, FH-Helsinki or FH-North Karelia, is present in more than 60% of the Finnish FH patients; there are no reports on their existence in other ethnic groups. Assays for these mutations were shown to markedly complement clinical diagnosis of FH in Finland. PMID- 1418920 TI - Molecular basis for apo A-IV polymorphisms. AB - Apolipoprotein (apo) A-IV is involved in the metabolism of triglyceride-rich lipoproteins and high-density lipoproteins and may thus play an important role in lipid metabolism, although the precise physiological function of apo A-IV is unknown. Structural and functional alterations of apolipoproteins, caused by a variety of mutations, have been shown to influence lipoprotein metabolism in several ways. Genetic studies are consistent with a single locus for apo A-IV with two main codominant alleles A-IV1 and A-IV2. The basis behind some of these electrophoretic variants has been determined on a molecular level by the aid of the polymerase chain reaction and sequencing of the amplified DNA. For instance, apo A-IV1 and apo A-IV2 alleles are explained by glutamine for histidine change of amino acid 360. Furthermore, several polymorphisms not leading to charge differences have been characterized. The genetic variability of apo A-IV may be of help in elucidating the functional role of apo A-IV in lipoprotein metabolism. In our study, the frequencies of the alleles due to Gln360-->His and Thr347-->Ser substitutions in a Finnish population sample were similar to those reported from other populations. In addition we have identified a novel genetic polymorphism of apo A-IV, Asn127-->Ser. In the Finnish population the asparagine for serine change of amino acid 127 was the most common apo A-IV polymorphism. There are no reports from other populations concerning this polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1418921 TI - Molecular genetics and genetic epidemiology of cardiovascular disease and diabetes. Introductory remarks: genetic models and statistical approaches. PMID- 1418922 TI - Twin studies in metabolic diseases. AB - The traditional role of twin studies has been to assess the relative role of genetic factors as a first step in defining the genetic architecture of complex traits. This has been based on the realization that monozygotic pairs (MZ) share all their genes, while dizygotic pairs (DZ) share 50% of their genes on average. Thus, greater similarity of MZ pairs compared to DZ pairs has been taken as prima facie evidence of the role of genetic factors. This is true provided the environmental similarity of MZ pairs is not greater than for DZ pairs for effects relevant to the trait in question. This first step in genetic studies was carried out long ago in many research areas, but not in others. More detailed knowledge of the genetic architecture of traits is then obtained by other means. In this paper, we give a brief overview of some results for metabolic diseases (ischaemic heart disease, hypertension, subarachnoid haemorrhage, NIDDM and IDDM) using the classical twin approach in a large, unselected population-based twin cohort. We also outline approaches to using twins that we believe will continue to be useful, particularly for the study of environmental effects. PMID- 1418923 TI - Multipoint analysis for radiation hybrid mapping. AB - Radiation hybrid mapping is a somatic cell genetic technique that permits construction of fine-structure maps of human chromosomes. Radiation hybrid mapping uses X-ray breakage of chromosomes to order genetic loci and to estimate distances between them. Cox and colleagues described radiation hybrid mapping and derived methods for locus ordering based on two-point statistical analysis of radiation hybrid mapping data. In this paper, I describe alternative non parametric and likelihood methods for radiation hybrid mapping that make use of information on many loci simultaneously, and efficiently include information on partially typed radiation hybrids. Locus orders are selected by minimum number of obligate chromosome breaks or maximum likelihood. I demonstrate the utility of these methods with an application to data on 14 markers and 99 hybrids for human chromosome 21. PMID- 1418924 TI - Empirical Bayes methods for testing associations with large numbers of candidate genes in the presence of environmental risk factors, with applications to HLA associations in IDDM. AB - Standard regression models for disease incidence data can be used to test for associations between a disease and measured genetic and environmental factors and their interactions. Complications arise when the gene is not observed, requiring segregation and linkage analysis approaches, or when the candidate gene(s) are found to be highly polymorphic, as in the HLA region. We propose a Bayesian approach to the latter problem, in which the log relative risks for all alleles at a given locus are taken to be independent and exchangeable, assuming there is no preferential zygotic assortment and negligible recombination. Multi-locus problems can be addressed either by adding exchangeable interaction terms or by adopting a multivariate prior for haplotype effects. Some simulations based on our current work on family studies of IDDM are discussed. PMID- 1418925 TI - Genetic epidemiology of insulin-dependent diabetes mellitus: international comparisons using molecular genetics. AB - International comparative molecular studies of insulin-dependent diabetes mellitus can be viewed from an immunogenetical and an epidemiological perspective. Each approach independently contributes to our knowledge concerning the etiology and prevention of the disease. However, the combination of these perspectives, representing an interface between molecular biology and epidemiology, will achieve more in terms of scientific advancement and public health than either perspective alone. An excellent example of the development of molecular epidemiology has been the evolution of international comparative research through the WHO Multinational Project for Childhood Diabetes. Case control molecular studies are currently being conducted to test the hypothesis that population variation in the frequency of HLA class II susceptibility alleles is the primary determinant of the global patterns of insulin-dependent diabetes mellitus incidence. Preliminary data suggest that this hypothesis is correct. Future international molecular epidemiological studies, encompassing host environment interactions, will lead to a better understanding of the relationships among specific risk factors within populations and across the world. Molecular epidemiology represents a new paradigm for studying the etiology and epidemiology of infectious and non-communicable diseases, and no doubt represents a major challenge for the 1990s. PMID- 1418926 TI - The future of multilocus linkage analysis. AB - Current limitations and needs of linkage analysis are discussed. Possible future developments in analysis methods and computer implementation are outlined. PMID- 1418927 TI - Transgenic animals in lipoprotein research. AB - Lipid metabolism is a complex system involving the interaction of several lipid transporting and -transferring serum proteins, enzymes regulating lipoprotein synthesis and modification, and lipoprotein receptors. Several epidemiological studies have demonstrated that many abnormalities in lipid metabolism are associated with coronary heart disease risk. There are at least 17 different genes that code for proteins directly involved in lipoprotein metabolism. Naturally occurring mutations in many of these genes have been described that affect either the quantity or the quality of these proteins. Such genetic alterations aid in the precise evaluation of the function of these gene products. Transgenic animal technology has made it possible to create genetic alterations and to study the consequences of overexpression of a gene and expression of a mutated protein, and also to study species-specific differences between proteins. PMID- 1418929 TI - The relation of communication and language development to mental retardation. PMID- 1418928 TI - Approaches to gene therapy of complex multigenic diseases: cancer as a model and implications for cardiovascular disease and diabetes. AB - The general concept of gene therapy is now well established and accepted by the medical, scientific and public policy communities, and is rapidly being implemented in human experimental studies. In addition to the initial models of single gene defects, target diseases have now come to include multigenic and multifactorial diseases such as human cancer, neurodegenerative diseases such as Parkinson's disease and firms of cardiovascular disease. While many conceptual and technical obstacles must still be overcome before therapy for disorders such as coronary artery disease and diabetes mellitus will easily be approached at the genetic level, the early results with several multigenic disease models gives some cause for optimism that gene therapies for even those complicated disorders will eventually become available. PMID- 1418930 TI - Stability of the intelligence quotient-language quotient relation: is discrepancy modeling based on a myth? AB - Diagnostic and service eligibility decisions are often made on the basis of the relation between assessments of cognitive ability and assessments of language ability. A discrepancy between cognitive and language performance, with cognition being higher, is thought to be a positive predictor of ability to benefit from intervention. This triage model assumes reasonable stability of cognitive and language measures over time. We evaluated the stability, over 1- and 2-year periods, of the relation between a cognitive measure and two language measures. We examined whether the cognitive-language relation for these measures changed significantly over time and whether children remained in the same service eligibility category, based on the discrepancy model, over time. Results indicated substantial changes in the cognitive-language relation over time. Children's eligibility for service, based on the discrepancy model, also fluctuated greatly over time. We conclude that a discrepancy model of triage based on broad cognitive and language measures is not an effective means of determining who should receive service. Alternative triage methods were presented. PMID- 1418931 TI - Development and training of referential communication in children with mental retardation. AB - In referential communication, the speaker must communicate to the listener about how a referent is different from other stimuli (i.e., employ the "difference rule"--Whitehurst & Sonnenschein, 1985). In Experiment 1 we compared use of the difference rule by children with and without mental retardation matched for Quick Test MA. Participants with mental retardation were less likely to employ the difference rule. Experiment 2 demonstrated that perceptual feedback training, which teaches use of the difference rule, enhances referential communication of children with mental retardation. PMID- 1418932 TI - Degree of associative relatedness and sentence processing by adolescents with and without mental retardation. AB - Previous research has suggested that individuals with mental retardation are less likely than individuals without mental retardation to access and incorporate information about the relations between words of sentences in the representations of those sentences in memory (e.g., Merrill & Bilsky, 1990; Merrill & Jackson, in press). A cued recall study and a semantic verification study were conducted to determine whether the magnitude of this group difference could be made smaller by increasing the degree to which the words in the sentences were semantically related. In both experiments, individuals with mental retardation exhibited an ability to utilize contextual information to a greater extent when the words were related. In the highly related conditions, the differences between groups was virtually eliminated. PMID- 1418933 TI - Profile of the prelinguistic intentional communicative behaviors of children with profound mental retardation. AB - The prelinguistic intentional communicative behaviors of 10 noninstitutionalized children with profound mental retardation were analyzed according to five profile parameters: communicative rate, communicative function, discourse structure, communicative means, and syllable shape. Subjects used a predominance of regulatory communicative functions, initiated discourse structure, gestural communicative means, and nontranscribable vocalizations/vocalizations without consonants. Findings were compared to previously reported data from children without mental retardation and institutionalized children with severe and profound mental retardation. PMID- 1418934 TI - Linguistic imitation in children with Down syndrome. AB - Rate of linguistic imitation by 48 children with Down syndrome was compared to that of 57 children without mental retardation. Both groups were taken from different corpora within the Child Language Data Exchange System (CHILDES, MacWhinney, 1991). All speech data were collected from spontaneous speech samples of mothers interacting with their children. Three types of imitative utterances (exact, expanded, and reduced) were coded using an automatic data analysis program called CHIP (Sokolov & MacWhinney, 1990). Multiple regression was utilized to test for group differences while controlling for variability in MLU. The results indicated that children with Down syndrome imitated slightly less, but the exact nature of this difference was related to language level and the source of the imitation. As MLU increased, the rate of imitation decreased at a much steeper rate for children without mental retardation than for children with Down syndrome. In addition, children with Down syndrome showed a different pattern of results for imitations of their mothers than for self-repeated imitations. The results suggest that children with Down syndrome develop differently with respect to linguistic imitation. PMID- 1418935 TI - Interdisciplinary strategies for treating dysphagia and eating disorders should include dentistry. PMID- 1418936 TI - A rapid in situ respiration test for measuring aerobic biodegradation rates of hydrocarbons in soil. AB - An in situ test method to measure the aerobic biodegradation rates of hydrocarbons in contaminated soil is presented. The test method provides an initial assessment of bioventing as a remediation technology for hydrocarbon contaminated soil. The in situ respiration test consists of ventilating the contaminated soil of the unsaturated zone with air and periodically monitoring the depletion of oxygen (O2) and production of carbon dioxide (CO2) over time after the air is turned off. The test is simple to implement and generally takes about four to five days to complete. The test was applied at eight hydrocarbon contaminated sites of different geological and climatic conditions. These sites were contaminated with petroleum products or petroleum fuels, except for two sites where the contaminants were primarily polycyclic aromatic hydrocarbons. Oxygen utilization rates for the eight sites ranged from 0.02 to 0.99 percent O2/hour. Estimated biodegradation rates ranged from 0.4 to 19 mg/kg of soil/day. These rates were similar to the biodegradation rates obtained from field and pilot studies using mass balance methods. Estimated biodegradation rates based on O2 utilization were generally more reliable (especially for alkaline soils) than rates based on CO2 production. CO2 produced from microbial respiration was probably converted to carbonate under alkaline conditions. PMID- 1418937 TI - The correlation of middle ear aeration with mastoid pneumatization. The mastoid as a pressure buffer. AB - Atelectatic ears, which by definition are poorly aerated, are also usually associated with poor mastoid pneumatization. On the other hand, otosclerotic patients, whose middle ears are usually exceptionally well aerated, also have excellent mastoid pneumatization. Three unusual cases are presented, in which partial atelectasis developed in stapedectomized patients. In each case the mastoid was later found to be nonpneumatized, and further analysis revealed that their stapes fixation had in effect most probably been of non-otosclerotic origin. Thus, although these three cases had at first appeared to represent exceptions to the general rule of otosclerotics having a well-aerated middle ear, in fact they support the association between atelectasis and poor pneumatization. The linkage of good middle ear aeration with large mastoid pneumatization and vice versa may suggest that the mastoid plays a role of a pressure buffer in the middle ear, which is a system of a gas pocket with fluctuating pressures. Also, otosclerosis may be considered to be an unlikely cause of conductive deafness in cases of poor pneumatization. PMID- 1418938 TI - Late effects of radiotherapy on hearing. AB - The effect of radiotherapy on hearing was studied in 30 patients who were treated by surgery and radiotherapy for a parotid neoplasm. Functions of the irradiated ear were compared with those of the non-irradiated ear in the same patient. Tympanometry showed a small but significant reduction of static compliance on the irradiated side when compared with the non-irradiated side. Audiometry showed a significant increase in hearing loss in the 1-2, 4-8 and 10-20 kHz ranges that increased with frequency. This hearing loss was mainly sensorineural in contrast to hearing loss at 250-500 Hz, where it was more of a conductive type. There appeared to be a significant dose-effect relation in sound perception at 4-8 kHz. Doses to the cochlea of less than 55 Gy seldom caused a hearing loss, in contrast to doses exceeding 65 Gy. Overall, radiotherapy was found to cause significant, mainly sensorineural hearing losses, which were partly dose-dependent. PMID- 1418939 TI - Mode of action of photodynamic therapy with sulfonated aluminum phthalocyanine in induced squamous cell carcinomas in animal models. AB - In order to investigate the mechanism of action of photodynamic therapy (PDT) with sulfonated aluminum phthalocyanine (AlSPc) in squamous cell carcinoma, animal experiments were performed in induced carcinomas of the mucosa of the hamster's cheek pouch and skin of the laboratory mouse. Histological examinations revealed signs of massive interstitial bleeding, indicating a vascular response to PDT with AlSPc. It was also possible to induce similar change adjacent to newly formed vessels at the margin of an inflammatory reaction in the cheek pouch of five hamsters in the absence of tumor cells. Implanted human squamous cell carcinoma cells in athymic nude mice showed that carcinoma cells removed immediately following PDT remained viable, while tumors left in situ became necrotic. These results suggest that the primary effect of PDT with AlSPc in vivo is not the malignant cell itself, but the vascular stroma of the tumor or in the immediate vicinity of the latter. PMID- 1418940 TI - Kinin generation following methacholine nasal airway challenge of non-allergic subjects. AB - Following nasal challenges with the muscarinic neurotransmitter methacholine in 14 patients with chronic non-allergic rhinitis, kinin generation was induced. This occurrence was inhibited by pretreatment with anticholinergic agents (ipratropium bromide) and by an overdose of neurotransmitter, indicating that a muscarinic receptor is stimulating the liberation of kinin. These observations suggest that patients with chronic non-allergic rhinitis exhibit cholinergic neurotransmitter-induced kinin generation. PMID- 1418941 TI - Changes in voice characteristics after uvulopalatopharyngoplasty. AB - Previous reports have warned that tonsillectomy or uvulopalatopharyngoplasty (UPPP) may alter patients' speech by increasing the amount of nasal resonance as well as by changing voice timbre due to enlargement of the vocal tract. However, very few objective investigations, excluding nasality problems, have been carried out. We studied eight patients who underwent surgery for UPPP and recorded pre- and postoperative speech. The speech samples were then rated by seven experienced listeners, and acoustic spectra of two long vowels,/a/ and /e/, were analyzed using a computer program (MacSpeech Lab II). The listeners were unable to make a distinction between pre- and postoperative voice samples in the recordings studied. Acoustic analysis showed that the fundamental frequency as well as the first and second formants remained essentially unchanged. Present findings show that UPPP should not have a significant effect on voice characteristics as long as excessive nasality is not produced. PMID- 1418942 TI - Maturation of binaural interaction components in auditory brainstem responses of young guinea pigs with monaural or binaural conductive hearing loss. AB - Reversible conductive hearing loss created during the first 4 weeks post partum caused marked alterations in the maturation of binaural interaction components in the auditory brainstem responses of guinea pigs. In untreated control animals all three components investigated demonstrated postnatal development in terms of latency shortening that was completed during the first 3 weeks of life. Plugging of both external ear canals caused a significant delay in the maturation of the late component DN2, where latency values of the controls were reached only 2 weeks after the end of the treatment, i.e. after 6 weeks of life. Monaural deprivation likewise led to a retarded development of peak latencies during the phase of imbalanced sensory input. After the end of the one-sided conductive hearing loss the maturation process was markedly enhanced, even resulting in latency values for DN2 and DP1 that were significantly shorter than those of the controls. This phenomenon persisted until the end of the study period and was the case for both plugged and untreated ears in this group of animals. The time course of latencies in two other groups of experimental animals which were deprived in the same way as adults suggests that the effects observed are due to a sensitive period in the maturation process of the auditory pathway. PMID- 1418943 TI - Long-term hearing results of one-stage tympanoplasty for chronic otitis media. AB - A study of 277 ears with chronic otitis media undergoing one-stage tympanoplasty has been carried out. The mean follow-up period was 6.4 years. Ears with intact ossicular chains were excluded. Ossiculoplasty was performed using autologous ossicles or cortical bone. Mean hearing gain was 10.8 dB. Closure of the postoperative air-bone gap to within 20 dB was achieved in 51% of cases. The best results were obtained in ears with intact stapes, while cholesteatomatous ears showed poorer results than other chronic ears. The present findings show that autologous ossicle and cortical bone are still suitable for ossicular reconstruction in chronic ears, especially when one-stage surgery is preferred. PMID- 1418944 TI - The anterior inferior cerebellar arterial network supplying the rat cochlea and its role in autoregulation of cochlear blood flow. AB - The sensitivity of the cochlea is dependent upon maintenance of a delicate homeostatic environment. One mechanism which participates in providing this environment is the autoregulation of cochlear blood flow. This autoregulation is ensured through the interaction of sympathetic, peptidergic and hemodynamic mechanisms. The current study demonstrates an adaptation that also participates in cochlear blood flow autoregulation. Specifically, an anterior inferior cerebellar arterial network is described and the relative contributions of each of its vessels to total cochlear blood flow is measured using laser Doppler flowmetry. The results show that each collateral vessel contributes to the blood supply of the cochlea and that reperfusion is accompanied by hyperemia. These findings suggest an adaptation that provides stable blood flow through redundancy and compensatory potential. Additionally, these observations have implications for experimental models of ischemia. PMID- 1418945 TI - Surgical lengthening of the short columella: division of the depressor septi muscles. AB - A new surgical procedure is described to correct the difficult problem of the short columella without resorting to cartilage grafts. The ready recourse to these grafts, so much in vogue at the present time in primary rhinoplasties, should be carefully and completely re-examined, since the final result very frequently yields no real benefits and may permanently deface the area from which the cartilage has been taken. The present technique combines trimming of the upper lateral nasal cartilages with approximation of the alar cartilages and excisions of the depressor septi muscles and/or contiguous orbicularis oris muscle. PMID- 1418946 TI - A histofluorescent study of sympathetic innervation of human palatine tonsils. AB - The glyoxylic catecholaminergic histofluorescence method was employed on human palatine tonsil specimens in order to study the sympathetic innervation present. One percent neutral red was used as a counterstain. Abundant sympathetic fibers were demonstrable around the blood vessels of the medulla and capsule. However, few sympathetic fibers were found around the vessels of the subepithelial connective tissue and interfollicular septa. In the areas of the follicle and extrafollicle where B and T lymphocytes were located, sympathetic fibers were not found. These findings indicate that if sympathetic innervation can affect T and B cells, it will do so indirectly. Results also show that there is a higher norepinephrine content in focally infected tonsils that is not due to hyperactivity of the sympathetic nerve, but may be due to other mechanisms. Finally surgical dissection at the capsule during tonsillectomy will reduce bleeding, perhaps because vessels there have an abundant sympathetic innervation that leads to good vessel contraction. PMID- 1418947 TI - Induction of transformation of human respiratory epithelium in vitro. Preliminary investigation. AB - Malignancy is the result of multistep transformational changes of normal somatic cells. In the case of respiratory epithelial malignancies this process lasts for several years. Many methods have been explored to mimic this process in an extracorporal model. In the present investigation we combined several of these methods. Organ cultures were prepared from tracheal specimens and were then consecutively treated with human papilloma virus, benzo(a)pyrene, methylnitronitrosoguanine and tetradecanoyl phorbol acetate. Identical numbers of organ cultures from the same specimen were maintained without exposure to carcinogens. After 6 weeks these cultures were further cultivated either in mixed cultures (MC) with autologous isotopic fibroblasts or under the kidney capsule of the nude mouse (SRC). These two methods were combined after a few months: MC cells were transplanted under the SRC or SRC transplants were explanted in cell culture. This long-term selection procedure revealed striking differences between control and treated organ cultures. Three-dimensional structures containing epithelial cells were isolated from both organ cultures but survived more than 3 months only from treated cultures. Only MC from treated organ cultures produced nodules under SRC. The incidence and morphology of the nodules in the SRC were directly related to carcinogen treatment, with more nodules with pronounced epithelial cell atypia obtained from treated organ cultures. MC and SRC showed the importance of a time factor for selecting cells with changed growth behavior- increased time increased the incidence of such cells. PMID- 1418948 TI - Clinical experience with the low-resistance Groningen button. AB - Since its introduction in 1980, the standard Groningen button prosthesis has been of proven value for post-laryngectomy voice rehabilitation. Its relatively high airflow resistance has, however, been the cause of failure in achieving good post laryngectomy tracheoesophageal shunt speech in some patients. The low-resistance Groningen button (LRGB) was therefore designed, thus reducing airflow resistance by 50% when compared to the standard device. The clinical performance of the LRGB, and the effect of prophylactic amphotericin, was assessed in 32 patients. The device lifetime, intratracheal phonatory pressures and patients' subjective acceptances of the prosthesis were recorded. Present findings showed that the majority of the patients preferred the LRGB as it required less effort to operate than the standard device. The intra-tracheal phonatory pressure was found to increase with time, but this change was prevented with the prophylactic use of amphotericin to inhibit concurrent colonization by Candida spp, which also helped to prolong the prosthesis lifetime. PMID- 1418949 TI - Hepatic regulation of renal function. AB - Despite apparently conflicting reports in the past, the bulk of evidence presently available points to a significant role for the liver in the regulation of renal function. Hepatic regulation of renal function may involve both a hepatorenal reflex and a liver-borne diuretic factor (LBDF and/or 'glomerulopressin'). The hepatorenal reflex is elicited by an increase in intrahepatic pressure, and/or certain amino acids in portal venous blood. It is transmitted by serotonin in the liver and presumably by noradrenaline in the kidney. It leads to a marked decrease in renal blood flow, glomerular filtration and urinary flow rate. The evidence for the LBDF is still circumstantial. The LBDF may be stimulated by glucagon and adenosine. It leads to a marked increase of renal blood flow, glomerular filtration rate and urinary output. Amongst the conditions presumed to be associated with altered hepatic regulation of renal function are postprandial hyperfiltration, and the deterioration of renal function which occurs in liver disease, cardiac insufficiency and cardiovascular shock. PMID- 1418950 TI - Position sense at the proximal interphalangeal joint is distorted in patients with rheumatoid arthritis of finger joints. AB - The results of this investigation demonstrate, using a position matching paradigm, that the ability of subjects to detect changes in the position of the proximal interphalangeal joint is impaired in patients with rheumatoid arthritis affecting this joint. In this group there is a systematic flexion bias in position judgements compared to an age- and sex-matched control group. This bias becomes progressively more pronounced at more extended positions. These results suggest that chronic inflammatory joint disease significantly alters proprioceptive sensations at finger joints and this may be due to the loss or distortion of afferent feedback from mechanoreceptors innervating the affected joint. PMID- 1418951 TI - A study of the expression of laminin in the spinal cord of the frog during development and regeneration. AB - In the present experiments, we have used an affinity-purified polyclonal antibody to laminin to determine the time course of expression of laminin in the central nervous system (CNS) of Rana temporaria tadpoles during normal development and during restoration of the dorsal columns of the spinal cord. Immunoblotting analysis indicated that in the peripheral nervous system (PNS) of adult frogs the antibody recognized proteins of molecular weights 350-400 and 205-220 kDa, corresponding to the A and B chains respectively of mammalian laminin. Immunohistochemistry with our antibody suggested that laminin was absent from the tadpole spinal cord, and did not appear even in the basal lamina of the blood vessels within the spinal cord until after metamorphosis. Furthermore, there was no evidence of laminin expression in the dorsal columns after hemisection of the spinal cord. However, throughout development laminin was present in basal lamina outside the CNS, in particular in the pial membranes, and in the basal lamina of blood vessels and sheath cells in the dorsal and ventral roots. Electron microscopy showed that the blood vessels of CNS capillaries had basal laminae throughout development that was morphologically indistinguishable from that seen in peripheral vessels. PMID- 1418952 TI - The role of cholecystokinin in inhibition of gastric emptying by peptone in the rat. AB - It is clear that the intestinal hormone cholecystokinin (CCK) inhibits gastric emptying, but doubts remain about the physiological significance of this action. Evaluation of the apparently conflicting data is complicated by the fact that little is known of the duration of action of CCK-releasing meals in delaying emptying. We have studied this issue by following the emptying of the second of two successive liquid test meals instilled into the stomach in conscious gastric fistula rats. Prior administration of peptone, but not saline, delayed the emptying of subsequently administered saline and delayed still further the emptying of subsequently administered peptone. The action of isotonic peptone lasted about 10 min from the initial instillation into the stomach. Radioimmunoassay of plasma CCK indicated a significant increase 5 min after intragastric peptone, and a still further rise occurred 5 min after administration of the second of two consecutive peptone meals; 21 min after the first meal, plasma CCK had returned to basal levels. Intravenous infusion of CCK in a dose that matched the inhibition of gastric emptying caused by peptone gave plasma concentrations about 35% higher than those seen 5 min after the second of two consecutive peptone meals. It is concluded that a liquid test meal of peptone delays gastric emptying in part through release of CCK and that the response lasts 10 min or less. The relatively short duration of action of endogenous CCK released by a single protein-rich meal in the rat should be kept in mind in interpreting the significance of studies on the physiology of CCK. PMID- 1418953 TI - Interdigestive gastric blood flow: the relation to motor and secretory activities in conscious dogs. AB - Blood flow in the left gastric artery was measured with an electromagnetic flowmeter in nine conscious beagle dogs. In the fasting state gastric motility and secretion exhibited periodical changes with an average cycle interval of 115.4 +/- 9.7 min. During a quiescent period, when gastric motility and secretion were minimal, the mean blood flow was stable at 33.9 +/- 3.8 ml/min. During the contracting phase each peristaltic contraction was coupled with a rapid fall and rise in blood flow (from 10.5 +/- 1.9 ml/min below to 21.2 +/- 3.8 ml/min above the precontraction levels) in 20-30 s. In addition there was a sustained elevation in blood flow (58.6 +/- 6.4 ml/min at the peak) lasting for 29.1 +/- 2.8 min. The onset of sustained blood flow elevation was preceded by that of motility in 63% of the cycles. In 23% of the cycles blood flow started to rise before the contracting phase began. Pepsin peaks coincided with blood flow peaks in two dogs and preceded the latter in the others. Feeding abolished periodic increases in motility and blood flow. It is concluded that left gastric arterial blood flow is not steady but exhibits dynamic changes in phase with periodic motor and secretory activities of the stomach in fasting conscious dogs. PMID- 1418954 TI - Effect of cortisol on blood pressure and vascular reactivity in the ovine fetus. AB - The aim of this study was to investigate the cardiovascular effects of exogenous cortisol in fetal sheep, (a) between 100 and 120 days of gestation when cortisol production is minimal and (b) after 130 days when endogenous plasma cortisol starts to rise. Chronically cannulated ovine fetuses (103-120 days, n = 9; 130 137 days, n = 7), received sequentially a 24 h infusion of vehicle (0.9% sodium chloride) and a 24 h infusion of cortisol at 100 micrograms/h. Blood pressure and heart rate changes to bolus injections each of angiotensin II and noradrenaline (0.2, 0.5, 1.0, 2.0 micrograms) were measured before and after the saline and cortisol infusions. Fetuses in each age group, served as additional controls receiving 48 h saline infusions. In both immature and mature age groups, the cortisol infusion increased basal fetal blood cortisol concentrations by 33.7 and 35.4 nmol/l respectively. In the immature group, cortisol, but not saline, caused significant 14.3 and 15.3% increases in basal systolic and diastolic pressures respectively. Basal blood pressure was higher in the mature group, but did not increase further despite the increase in cortisol levels. Furthermore, vascular responsiveness to angiotensin II but not to noradrenaline was significantly enhanced following the cortisol infusion, at both ages. Fetal heart rate did not change following the cortisol infusion. Exogenous cortisol contributes to the regulation of fetal blood pressure in the immature fetus, when other mechanisms have not developed. Cortisol might achieve this, in part, by enhancing vascular sensitivity to angiotensin II. PMID- 1418955 TI - Myoplasmic Mg2+ concentration in Xenopus muscle fibres at rest, during fatigue and during metabolic blockade. AB - Intracellular free Mg2+ concentration ([Mg2+]i) was measured in isolated single fibres of Xenopus muscle using the fluorescent Mg2+ indicator furaptra. In resting muscle the [Mg2+]i was 1.7 mM in a Mg(2+)-free Ringer solution. There was no significant change in [Mg2+]i over 2 h in Mg(2+)-free Ringer solution. Elevating extracellular [Mg2+] to 40 mM for 5 min caused a small rise (0.13 mM) in [Mg2+]i. There was no detectable rise in [Mg2+]i after 5 min in Na(+)-free Ringer solution. These results suggest that the membrane is relatively impermeable to Mg2+ and that there was no detectable Na(+)-Mg2+ exchange over 5 min. When muscle fibres were fatigued by repeated tetani continued until force declined to about 40% of control, [Mg2+]i showed characteristic changes. During the early period of fatigue when force first showed a small decline and then became almost stable, [Mg2+]i was unchanged; during the final period of fatigue when force declined more rapidly, [Mg2+]i increased by 0.8 mM. Recovery of [Mg2+]i took about 30 min. Recovery of force was complex: tetanic force first declined (post-contractile depression) and then slowly recovered to control. Since the minimum force occurred at about the time when [Mg2+]i had recovered, it seems unlikely that post-contractile depression is caused by elevated [Mg2+]i. Rigor, produced by inhibiting oxidative phosphorylation and glycolysis, was associated with a larger increase (1.6 mM) in [Mg2+]i than fatigue. The rise in [Mg2+]i during fatigue and metabolic blockade could be explained as release of Mg2+ normally bound to ATP. A model of the metabolic changes and the resulting increase in [Mg2+]i explains our results reasonably well. PMID- 1418956 TI - Electrical resistances of cultured bovine arterial endothelium in solutions of various resistivities. AB - Relationships between the electrical resistance (Rm) of cultured endothelium and the resistivity (rho) of the bathing solution have been investigated, using eight monolayers of bovine arterial endothelium. Bathing solutions of differing rho were prepared by mixing culture medium and isosmolar (290 mM) sucrose in various proportions. Relationships between 1/Rm and 1/rho were linear, as predicted, with a mean 1/Rm intercept of zero. The slopes of the relationships give a mean fractional area per unit path length (Ap/delta chi) of 12.7 cm-1 for the paracellular pathways of the cultured endothelium. This resembles previous estimates of Ap/delta chi for mammalian endothelium in arteries. The 1/Rm intercept of zero indicates that the major electrical conducting pathways of cultured arterial endothelium are paracellular. PMID- 1418957 TI - The protective effect of damaging eccentric exercise against repeated bouts of exercise in the mouse tibialis anterior muscle. AB - Using a damaging eccentric exercise regime of the mouse tibialis anterior (TA) muscle we have investigated the extent and time course of protection afforded by one bout of exercise against damage resulting from a second bout of activity. Maximal force and fibre morphology were preserved if the exercise was repeated within 21 days, but by 84 days muscles once again became susceptible to damage. Low-frequency force loss had a shorter time course of protection against repeated exercise, lasting less than 21 days. The results provide evidence for different mechanisms contributing to the development of muscle damage following eccentric exercise and provide a basis for characterizing the adaptive response of muscle to damaging exercise. PMID- 1418958 TI - Intracerebroventricular angiotensin II-induced thirst and sodium appetite in rat are blocked by the AT1 receptor antagonist, Losartan (DuP 753), but not by the AT2 antagonist, CGP 42112B. AB - In the rat, intakes of water and 1.8% NaCl induced by I.C.V. angiotensin II were inhibited by prior I.C.V. injection of the angiotensin subtype 1 receptor antagonist, Losartan, but not by the subtype 2 receptor antagonist, CGP 42112B. Drinking induced by I.C.V. carbachol was unaffected by either antagonist. PMID- 1418959 TI - An investigation into the extent to which flare in human skin crosses the mid line. AB - We investigated whether flare crossed the mid-line in various positions in humans using laser Doppler flowmetry to confirm visual observations. On the back and forehead, flare crossed the mid-line. However, on the posterior part of the neck, flare did not cross the mid-line, an observation that may be related to the elongated shape of flare in this region. PMID- 1418960 TI - Precise and efficient construction of synthetic genes. PMID- 1418961 TI - PCR primers specific for detection of a rat repetitive sequence. PMID- 1418962 TI - A fast and simple technique for sequencing plasmid DNA with Sequenase using heat denaturation. PMID- 1418963 TI - Purification of the two strands of a DNA fragment by polyethylene glycol precipitation. PMID- 1418964 TI - Purification of nucleic acids by filtration through a hydrophobic membrane. PMID- 1418965 TI - Ultrafast plasmid DNA preparation for rapid transformation. PMID- 1418966 TI - Optimized assays for quantifying transient expressions of co-transfected beta galactosidase and CAT reporter genes. PMID- 1418967 TI - Thiols interfere with chloramphenicol acetyltransferase assays. PMID- 1418968 TI - Simple modifications of a protein immunoblotting protocol to reduce nonspecific background. PMID- 1418969 TI - Rapid immunological screening for protein expression in yeast transformants. PMID- 1418970 TI - A simple method of plasmid transformation of E. coli by rapid freezing. PMID- 1418971 TI - Cloning of integration sites of retroviruses bearing drug resistance markers. PMID- 1418972 TI - Whole mount in situ detection of low abundance transcripts of the myogenic factor qmf1 and myosin heavy chain protein in quail embryos. AB - We describe a whole mount in situ hybridization procedure to detect and localize low abundance transcripts (qmf1) and myosin heavy chain proteins in quail embryos. The critical factor in transcript detection was the extent of proteinase K digestion. Optimal digestion increased probe accessibility and reduced background. The use of digoxigenin-labeled probes and immunological detection with anti-digoxigenin-alkaline phosphatase conjugated antibody allowed signal development in 6-10 h, unlike the 7 days required using 35S-labeled probes. Myosin heavy chain proteins were detected using immunofluorescence and confocal laser scanning microscopy to allow precise localization of signal within developing embryos. PMID- 1418973 TI - Single-cell cDNA-PCR: removal of contaminating genomic DNA from total RNA using immobilized DNase I. AB - A procedure utilizing immobilized DNase I that allows the efficient amplification of cDNA by PCR from a single cell in the absence of contaminating genomic DNA is described. DNase I treated, total RNA derived from single cells was reverse transcribed into cDNA followed by PCR using beta-actin and c-fos specific primers that recognize different exons of the respective genes. Amplification products corresponding to cDNA, but not to genomic sequences, were detected after treatment with immobilized DNase I in samples previously shown to be contaminated with genomic DNA. This method allows the efficient removal of DNA contaminating total RNA derived from a single cell. PMID- 1418974 TI - A simple and rapid method for screening transformant yeast colonies using PCR. AB - A simple and rapid procedure for screening transformant yeast colonies is described. In this method, a trace amount of plasmid DNA is isolated from a small amount of yeast cell mass; then, the presence of the exogenous DNA in each yeast colony is detected by PCR amplification. PMID- 1418975 TI - DNA elution and amplification by polymerase chain reaction from dried blood spots. AB - A quick, sensitive and easily automatizable method for PCR amplification of genomic DNA eluted from dried blood spots is described. DNA is eluted from a 3-mm spot routinely used for neonatal screening of inherited diseases either by boiling or by sonication. A preliminary and brief spot-autoclaving step is mandatory to ensure optimal and reproducible PCR amplifications. Only 1% of the eluted DNA is required for PCR analysis allowing the execution of multiple genetic tests on the same blood spot. The method has been successfully applied to the detection of a known phenylketonuria-causing mutation and will facilitate the analysis of the genetic repository provided by Guthrie's cards stored in neonatal screening laboratories. PMID- 1418976 TI - Periodic acid/Schiff staining of glycoproteins immobilized on a blotting matrix. AB - A simple and sensitive method for the detection of glycoproteins and glycopeptides in solution and in polyacrylamide gels is described. This method combines the well-known periodic acid/Schiff stain with protein blotting. Compared with direct staining of a polyacrylamide gel, the sensitivity is considerably increased. Using a set of glycoproteins, we have found the sensitivity to be about 4 ng carbohydrate. PMID- 1418977 TI - A visual method for rapid screening of xylose-fermenting ethanolic strains of Klebsiella pneumoniae. AB - A simple and rapid screening method for selecting hyper-ethanolic strains of Klebsiella pneumoniae is described. The method involves a novel biological screening marker, namely, the yeast Candida ethanothermophilum. The screening marker was seeded on an agar plate to the surface of which agar blocks, each containing a colony of K. pneumoniae, were subsequently fixed. This seeded plate lacked sources of carbon and energy. Ethanol formed in the agar blocks by the K. pneumoniae colonies diffused into the seeded medium and served as a carbon and energy source for the ethanotrophic yeasts. Colonies of yeasts appeared around the agar blocks in regions of ethanolic diffusion. Hyper-ethanolic strains of K. pneumoniae were thus selected on the basis of the number of colonies of the screening marker that appeared around the blocks containing the ethanolic colonies of K. pneumoniae. PMID- 1418978 TI - Production of recombinant porcine tumor necrosis factor alpha in a novel E. coli expression system. AB - DNA sequences encoding porcine tumor necrosis factor alpha (TNF alpha) were reconstructed from a genomic-derived PCR product for expression in Escherichia coli. A synthetic DNA primer containing most of exon III was fused to exon IV sequences by means of PCR. The fused product was then inserted into the novel FLAG vector by restriction and ligation. This initial recombinant construct was propagated in single-strand form through use of a helper phage and subjected to oligonucleotide-directed mutagenesis for the purpose of introducing additional coding sequences from exons II and III. The final construct encoded a fusion protein consisting of the Omp-A signal peptide, a seven-amino acid FLAG peptide and the soluble form of porcine TNF alpha. Bacteria containing this construct produced a protein which was recognized by anti-FLAG monoclonal antibody in Western blots and which was purified by anti-FLAG immunoaffinity chromatography. The purified material was cleaved with enterokinase to remove the FLAG peptide. Both the enterokinase-cleaved form and the uncleaved form were shown to have TNF activity in a WEHI cell cytotoxicity assay. PMID- 1418979 TI - A PCR-based method for manipulation of the vaccinia virus genome that eliminates the need for cloning. AB - A general method is described for altering specific genes of vaccinia virus (VV). We demonstrate and evaluate the procedure by gene inactivation, using a dominant selectable marker in conjunction with recombinant polymerase chain reaction (PCR). Primers based on the sequence of the target gene enable amplification of flanking arms and their subsequent attachment to the gpt cassette that confers resistance to mycophenolic acid. Linear PCR constructs are transfected into cells infected with wild-type vaccinia virus. Mutant viruses with gpt inserted into the target gene by homologous recombination are then selected by growth in the presence of MPA. This technique was applied to the vaccinia virus thymidine kinase gene and compared to the traditional method of constructing gpt-containing plasmids by cloning. The PCR scheme was found to be highly efficient and could theoretically be used to insert any foreign DNA element into any nonessential target gene for which partial or complete sequence information is available. The procedure can potentially be used for a wide variety of genetic modifications, including the insertion of foreign genes, with poxviruses and other DNA viruses. Genomes of microorganisms, such as bacteria and yeast that can be transformed with linear DNA, are also candidates for manipulation by this methodology. PMID- 1418980 TI - A rapid and reliable method to create tandem arrays of short DNA sequences. AB - Tandemly polymerized regulatory elements, antisense RNA segments or ribozymes are potentially useful in selective gene silencing. However, existing methods of tandemly polymerizing short DNA segments are laborious. We present a procedure that can create cloned arrays of 40-70 monomer units in two steps. We have created long arrays of regulatory elements and potential ribozyme sequences. Silencing of human immunodeficiency virus (HIV-1) activation by tandem arrays of a regulatory element in human immune system cells and in other human and monkey cells is discussed. PMID- 1418981 TI - Bacterial single-chain antibody fragments, specific for carcinoembryonic antigen. AB - We have produced single-chain antibody (scFv) fragments in bacteria specific for carcinoembryonic antigen (CEA). Polymerase chain reaction (PCR) was used for the cloning and modification of the heavy and light variable regions (VH and VL) of the mouse monoclonal antibody (MAb) CB-CEA.1. A 14-amino acid linker was used in the synthesis of the scFv gene. The VH and VL regions were amplified from cDNA by PCR using 5' end FR1 and 3' end constant region primers, and then sequenced. VH was then amplified by PCR using an exact 5' end FR1 primer, and a phosphorylated (PP) 3' end primer for J2 that also encoded the first 7 amino acids of the linker. VL was amplified with a PP 5' end primer for FR1, also encoding the remaining 7 amino acids of the linker, and a 3' end primer for J5, plus a stop codon and a BglII restriction site. The fragments were ligated and reamplified with the PP VH 5' and VL 3' end primers. The VH-linker-VL structure was blunt cloned into expression vectors bearing the tryptophan promoter and pelB or ompA signal peptide sequences. Culture supernatant, bacteria pellet and periplasm preparations were assayed in Western blot and a protein of about 27 kDa was identified with rabbit antibodies specific for the Fab of CB-CEA.1. Bacterial supernatant and periplasm preparations also inhibited the recognition of CEA by HRP-labeled CB-CEA.1 in enzyme-linked immunosorbent assay (ELISA). Periplasm preparations were purified by affinity chromatography with specific anti idiotypic MAbs. The Western blot of the eluates identified a protein of approximately 27 kDa that blocked the recognition of CEA by HRP-labeled CB-CEA.1 in ELISA. The VH-linker-VL structure was cloned into a vector bearing the lacZ promoter and the pelB signal peptide. The recombinant bacterial clones also expressed about 27 kDa scFv, specific for CEA. PMID- 1418982 TI - Cyclin B in fish oocytes: its cDNA and amino acid sequences, appearance during maturation, and induction of p34cdc2 activation. AB - Under the influence of maturation-inducing hormone (MIH) secreted from follicle cells, oocyte maturation is finally triggered by maturation-promoting factor (MPF), which consists of a homolog of the cdc2+ gene product of fission yeast (p34cdc2) and cyclin B. Two species of cyclin B clones were isolated from a cDNA library constructed from mature goldfish oocytes. Sequence comparisons revealed that these two clones are highly homologous (95%) and were found to be similar to Xenopus cyclin B1. Using monoclonal antibodies against Escherichia coli-produced goldfish cyclin B and the PSTAIR sequence of p34cdc2, we examined the levels of cyclin B and p34cdc2 proteins during goldfish oocyte maturation induced in vitro by 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one (17 alpha, 20 beta-DP), a natural MIH in fish. Protein p34cdc2 was found in immature oocyte extracts and did not remarkably change during oocyte maturation. Cyclin B was not detected in immature oocyte extracts and appeared when oocytes underwent germinal vesicle breakdown. Cyclin B that appeared during oocyte maturation was labelled with [35S]methionine, indicating its de novo synthesis. Introduction of E. coli produced cyclin B into immature oocyte extracts induced p34cdc2 (MPF) activation. Although the possibility that immature goldfish oocytes contain an insoluble cyclin B is not completely excluded, these results strongly suggest that 17 alpha, 20 beta-DP induces oocytes to synthesize cyclin B, which in turn activates preexisting p34cdc2, forming active MPF. PMID- 1418983 TI - Unexpected position-dependent expression of H-2 and beta 2-microglobulin/lacZ transgenes. AB - In order to study sequences involved in the developmentally regulated and tissue specific expression of the class I Major Histocompatibility Complex (MHC) genes, we have constructed several H-2/lacZ transgenic lines in which the 5' regulatory sequences of the H-2Kb gene are linked to the Escherichia coli beta-galactosidase (lacZ) gene. In five H-2/lacZ lines, the pattern of lacZ expression, detected histochemically varied greatly from line to line. None of the H-2/lacZ transgenes were transcribed in cells normally expressing a high level of endogenous H-2 molecules, although these H-2 regulatory sequences have been shown to be sufficient to drive tissue-specific expression of other reporter genes. Interestingly, when constructs containing 5' beta 2-microglobulin (beta 2m) regulatory sequences linked to lacZ were used to derive transgenic lines, similar results were obtained. A survey of lacZ labeling in H-2/lacZ and beta 2m/lacZ transgenic mice strongly suggests that these transgenes are very sensitive to position effect, lacZ expression being controlled by endogenous chromosomal regulatory elements specific for each insertion site. Here we describe the complex pattern of lacZ expression in the different transgenic lines during development; we discuss the unusual properties of these transgenes and underline their potential use for developmental studies and characterization of genomic sequences involved in spatiotemporal gene expression. PMID- 1418984 TI - Secretion of bovine alpha-lactalbumin into the milk of transgenic rats. AB - Bovine alpha-lactalbumin (b alpha LA) gene prepared by polymerase chain reaction was introduced into rat genomes by microinjection. Out of 17 transgenic rat lines, 11 secreted b alpha LA into their milk at concentrations higher than 0.2 micrograms/ml. Of these, three lines secreted b alpha LA at concentrations higher than those in bovine milk. The highest concentration of b alpha LA secreted into rat milk was 2,400 micrograms/ml. PMID- 1418985 TI - Purification and partial characterization of the 17 kDa sperm coating protein from boar seminal plasma. AB - Sperm coating proteins of 16, 17, and 19 kDa have been purified from boar seminal plasma. The 17 kDa protein has been identified as an antigen recognized by monoclonal antibody ACR.3 and is thus identical to low molecular mass zona pellucida binding protein from boar spermatozoa (Moos et al., 1990). The 17 and 19 kDa proteins are glycosylated and tend to form hetero-complexes. The 17 kDa ACR.3 antigen is sequentially released from the sperm cell surface during capacitation and, after induction of the acrosome reaction, the 16 kDa form was also observed. Immunocytochemical studies on boar reproductive tissues have suggested that the seminal vesicle epithelium may be the source of these proteins. PMID- 1418986 TI - F-actin in guinea pig spermatozoa: its role in calmodulin translocation during acrosome reaction. AB - The presence of actin has been determined in mammalian spermatozoa. However, its function in these cells is still almost unknown. Only in boar spermatozoa has evidence for F-actin and a possible function for it been presented. In this work, actin distribution and F-actin were determined in uncapacitated, capacitated, and acrosomal-reacted guinea pig spermatozoa, by means of monoclonal and polyclonal antibodies, using an indirect immunoperoxidase technique, and by the use of rhodamine-phalloidin. With the last probe we found filamentous actin in these cells. By both techniques, actin was detected in the acrosome and in the entire tail. In some cells with acrosomal reaction, actin was also detected in the equatorial and in the postacrosomal regions. SDS-PAGE and Western blots immunostained with monoclonal and polyclonal anti-actin antibodies confirmed the presence of actin in extracts of guinea pig spermatozoa. Actin was also detected in preparations of Percoll-purified spermatozoa. We have communicated that guinea pig spermatozoa show a change on calmodulin location during the acrosome reaction. They present it first in the equatorial region and later in the postacrosomal region. To determine if F-actin participates in this calmodulin translocation, we studied the effect of cytochalasin D. It was found that the number of cells with calmodulin in the equatorial region increased in the presence of cytochalasin D while the number of cells with calmodulin in the postacrosomal region decreased. We also found that after cytochalasin D treatment acrosome loss was increased and sperm motility was slightly inhibited. Our results suggest that actin participate in calmodulin translocation to the postacrosomal region during acrosome reaction, in maintaining the acrosome structure, and perhaps also in sperm motility. PMID- 1418987 TI - Porcine oocyte zona pellucida M(r) 55,000 glycoproteins: identification of O glycosylated domains. AB - The distribution of O-linked oligosaccharides on the M(r) 55,000 glycoproteins, ZP3 alpha and ZP3 beta, of the porcine oocyte zona pellucida was examined. Purified preparations of endo-beta-galactosidase digested ZP3 alpha and ZP3 beta were reduced and carboxamidomethylated and digested with trypsin. When the trypsin digests were mapped by HPLC, each glycoprotein yielded only one N acetylgalactosamine containing glycopeptide. Purification of the O-glycopeptides was achieved by a two-step protocol. Tryptic digests were applied to jacalin agarose and specifically-bound O-glycopeptides (alpha OGP and beta OGP) were eluted with buffer containing 50 mM alpha-methylgalactoside as the haptenic sugar. Further purification of each O-glycopeptide was accomplished by reverse phase HPLC. Purified O-glycopeptides were characterized with respect to amino acid and carbohydrate compositions and sequenced by automated Edman degradation; alpha OGP was a 41-residue glycopeptide with three O-linked sugar chains. Sequence comparisons revealed a 75% identity between alpha OGP and a corresponding segment of rabbit rec55 zona protein; beta OGP was a 25-residue glycopeptide characterized by the presence of one N-linked and five O-linked sugar chains and a trypsin-resistant internal arginine residue. Sequence alignments revealed an 80% or greater identity between beta OGP and internal peptides of mouse, hamster and human ZP3 zona proteins. These studies demonstrate that in the case of ZP3 alpha and ZP3 beta, the pig homologues of rabbit rec55 and mouse ZP3, respectively, O-linked oligosaccharides are confined within delimited domains rather than widely dispersed on the polypeptide backbone. Such clustering of O-linked oligosaccharides may represent an essential determinant of the structure and biological activity of zona proteins. PMID- 1418988 TI - Detection of chromosome 17- and X-bearing human spermatozoa using fluorescence in situ hybridization. AB - Fluorescence in situ hybridization (FISH) with DNA probes specific to chromosomes 17 and the X has been applied to human ejaculated sperm. After sperm nuclei were decondensed with EDTA and DTT, biotinylated alpha satellite DNA probes TR17 and TRX were separately used on preparations from thirteen healthy donors. After hybridization 96% of sperm were labelled with the TR17 probe and 48% of sperm were labelled with the TRX probe. Frequencies of 0.33% disomic 17 and 0.29% disomic X sperm were found. The frequencies of diploid sperm were assessed as 0.37% using the TR17 probe and 0.20% using the TRX probe which labelled only one half of the sperm; after correcting the result from the X-probe to 0.40% the two frequencies are very similar. PMID- 1418989 TI - Structural changes in sperm from the fiddler crab, Uca tangeri (Crustacea, Brachyura), during the acrosome reaction. AB - The acrosome reaction (AR) was induced in sperm from the brachyuran crustacean Uca tangeri either by mixing male and female gametes in filtered seawater or by treating the spermatozoa with the divalent cation ionophore A23187. This latter method provided a sufficient number of reacted spermatozoa to allow a detailed ultrastructural study of the AR. The process consists of two separate phases: a) initial release of the acrosomal vesicle contents, and b) further elongation of the acrosomal filament, which causes reversal of the rigid capsule limiting the acrosomal vesicle contents. The elongate acrosomal filament consists of an apical perforatorium and a basal columnar structure called here the proximal piece. The former derives from the perforatorium of the uninduced sperm stage with only small ultrastructural changes. The proximal piece forms from myelin-like membrane layers which are initially distributed all around the subacrosomal region and then accumulate in a column at the perforatorial base, thus promoting a sudden forward projection of the perforatorium. The AR in brachyurans is thought to be a passive mechanism that utilizes the negative pressure exerted on the nucleus- caused by emptying of the acrosomal vesicle--for an organized accumulation of membrane-rich material immediately behind the perforatorium, with the final result of the raising of a 3 microns long acrosomal filament. PMID- 1418990 TI - A freezing and thawing method of hamster oocytes designed for both the penetration test and chromosome assay of human spermatozoa. AB - Superovulated hamster oocytes were cryopreserved and thawed according to our carefully designed procedures. More than 90% (92 +/- 4%) of oocytes survived freezing and thawing. They were proven to be well conserved, showing excellent performance comparable to freshly ovulated oocytes in the human sperm penetration test (proportion of penetrated ova: 94.7% vs. 93.6%) and human sperm chromosome analysis (proportion of metaphasic ova: 81.8% vs. 83.6%). There was no statistically significant difference in the incidences of sperm chromosome aberrations between assays using fresh and frozen-thawed oocytes. In addition, there was no statistically significant increase of aberrations in female pronuclear (hamster) chromosomes. This freezing-thawing method was found to be reliable, yielding viable hamster oocytes of high quality. PMID- 1418991 TI - Vitrification of mouse oocytes using short cryoprotectant exposure: effects of varying exposure times on survival. AB - The effects on oocyte viability of varying the duration of exposure to cryoprotectants before rapid cooling to -196 degrees C were examined, using the vitrification protocol of Nakagata. A very short exposure (15 sec) was found to be optimal, resulting in an overall rate of development from vitrified oocytes to hatching blastocysts of 31.8%. Very high rates of survival (77-89%) of oocytes exposed to the cryoprotectant media, but without the vitrification, together with extreme variability in results between straws in the vitrified groups, suggest that losses in viability during vitrification may result from ice damage during devitrification of the medium. PMID- 1418992 TI - Behavior of sperm nuclei incorporated into parthenogenetic mouse eggs prior to the first cleavage division. AB - When artificially activated mouse eggs are inseminated in the middle of the first cell cycle, sperm nuclei remain condensed until the first mitosis. During mitosis of the first cleavage division sperm nuclei decondense, subsequently recondense and are passively displaced to the daughter blastomeres. In the 2-cell embryos sperm nuclei form interphase nuclei which are able to replicate DNA and to condense into discrete chromosomes during the following mitotic division. These observations suggest that the mitotic cytoplasm of 1-cell embryos creates similar conditions for the transformation of sperm nuclei into male pronuclei as the cytoplasm of metaphase II oocytes. PMID- 1418993 TI - A study by in situ hybridization of the stage of appearance and disappearance of the transition protein 2 and the mitochondrial capsule seleno-protein mRNAs during spermatogenesis in the mouse. AB - Transition protein 2 is a basic chromosomal protein which functions as an intermediate in the replacement of histones by protamines, and the mitochondrial capsule seleno-protein is a constituent of the outer membrane of mitochondria which functions in constructing the mitochondrial sheath surrounding the flagellum. To determine precisely the stages in spermatogenesis when these mRNAs are present, paraffin sections of sexually mature testes were hybridized to 35S- and 3H-labeled antisense RNAs and exposed to autoradiographic emulsion. The cell types hybridizing to probes in situ were determined by staining with hematoxylin and periodic acid Schiff. The in situ hybridizations reveal that the transition protein 2 mRNA is first detectable in step 7 round spermatids, persists at high levels through step 13, and is degraded before step 14. By contrast, the mitochondrial capsule seleno-protein mRNA is first detected in step 3 round spermatids and persists at high levels until step 16, the end of spermiogenesis. The mitochondrial capsule seleno-protein mRNA appears to be expressed only in haploid cells since low levels could not be detected in Northern blots of RNA from pachytene primary spermatocytes from 18 day prepubertal mice. These results demonstrate that the transition protein 2 and mitochondrial capsule seleno protein mRNAs are transcribed and degraded at different times during the haploid phase of spermatogenesis. PMID- 1418994 TI - Protein dynamics in sperm membranes: implications for sperm function during gamete interaction. AB - A number of mammalian sperm plasma membrane antigens have been implicated as playing a functional role in sperm-egg interaction, by virtue of the fact that antibodies against these antigens interfere with fertilization. Two such mouse sperm plasma membrane antigens are M42, a 200/220 kD glycoprotein doublet, and M5, a 150-160 kD glycoprotein. We show that both of these antigens are concentrated on the posterior region of caudal epididymal and capacitated mouse sperm heads and are relatively diffusible, as determined by fluorescence recovery after photobleaching measurements (D = 3-8 x 10(-9) cm2/s with approximately 23% diffusing). Crosslinking of these antigens with bivalent antibodies causes them to redistribute into the anterior region (acrosomal crescent) of the sperm head. In contrast, we describe a third antigen, P220, which is also localized to the posterior region of the sperm head on caudal epididymal sperm but which exhibits very little diffusion and does not redistribute upon crosslinking. Bivalent anti M42 blocks the ZP3-induced acrosome reaction. We have found that monovalent Fab fragments of anti-M42 do not block the ZP3-induced acrosome reaction, but that inhibition is restored by addition of a second antibody which crosslinks the Fabs. Thus, crosslinking is required for both inhibition of the acrosome reaction and redistribution. This suggests that redistribution of antigen away from the posterior region of the head may be part of the mechanism of inhibition of the ZP3-induced acrosome reaction. PMID- 1418995 TI - castor encodes a novel zinc finger protein required for the development of a subset of CNS neurons in Drosophila. AB - Using an enhancer detection screen, we have identified castor, a new gene required for embryonic CNS development in Drosophila. Embryos that lack castor expression have a diminished CNS axonal network and express engrailed aberrantly late in CNS development. castor is unique among the previously described genes involved in Drosophila neurogenesis in that its expression is restricted to a subset of delaminated CNS neuroblasts and to ventral midline glial precursor cells. The putative castor gene product contains a novel zinc-binding domain and multiple transcriptional activation domains, suggesting that it acts as a transcription factor necessary for the development of a subset of CNS neuronal precursors. PMID- 1418996 TI - Intracellular movements of fluorescently labeled synaptic vesicles in frog motor nerve terminals during nerve stimulation. AB - We stained synaptic vesicles in frog motor nerve terminals with FM1-43 and studied changes in the shape and position of vesicle clusters during nerve stimulation. Each stained vesicle cluster appeared as a fluorescent spot. During repetitive nerve stimulation the spots gradually dimmed, most without changing shape or position. Occasionally, however, a spot moved, appearing in some cases to stream toward and coalesce with a neighboring spot. This suggests the existence of translocation mechanisms that can actively move vesicles in a coordinated fashion between vesicle clusters. Within single clusters, we saw no signs of such directed vesicle movements. Fluorescent spots in terminals viewed from the side with a confocal microscope did not shrink toward the presynaptic membrane during nerve stimulation, but dimmed uniformly. This suggests that vesicles continuously mix within a cluster during destaining and provides no evidence of active vesicle translocators within single vesicle clusters for moving vesicles to the presynaptic membrane. PMID- 1418997 TI - Transgenic mice with a rhodopsin mutation (Pro23His): a mouse model of autosomal dominant retinitis pigmentosa. AB - We inserted into the germline of mice either a mutant or wild-type allele from a patient with retinitis pigmentosa and a missense mutation (P23H) in the rhodopsin gene. All three lines of transgenic mice with the mutant allele developed photoreceptor degeneration; the one with the least severe retinal photoreceptor degeneration had the lowest transgene expression, which was one-sixth the level of endogenous murine rod opsin. Of two lines of mice with the wild-type allele, one expressed approximately equal amounts of transgenic and murine opsin and maintained normal retinal function and structure. The other expressed approximately 5 times more transgenic than murine opsin and developed a retinal degeneration similar to that found in mice carrying a mutant allele, presumably due to the overexpression of this protein. Our findings help to establish the pathogenicity of mutant human P23H rod opsin and suggest that overexpression of wild-type human rod opsin leads to a remarkably similar photoreceptor degeneration. PMID- 1418998 TI - Fasciclin IV: sequence, expression, and function during growth cone guidance in the grasshopper embryo. AB - Monoclonal antibody 6F8 was used to characterize and clone fasciclin IV, a new axonal glycoprotein in the grasshopper, and to study its function during growth cone guidance. Fasciclin IV is dynamically expressed on a subset of axon pathways in the developing CNS and on circumferential bands of epithelial cells in developing limb buds. One of these bands corresponds to the location where the growth cones of the Ti1 pioneer neurons make a characteristic turn while extending toward the CNS. Embryos cultured in the 6F8 antibody or Fab exhibit aberrant formation of this axon pathway. cDNA sequence analysis suggests that fasciclin IV has a signal sequence; long extracellular, transmembrane, and short cytoplasmic domains; and shows no homology with any protein in the available data bases. Thus, fasciclin IV appears to be a novel integral membrane protein that functions in growth cone guidance. PMID- 1418999 TI - Single amino acid substitutions in EGF-like elements of Notch and Delta modify Drosophila development and affect cell adhesion in vitro. AB - Notch locus EGF-like element mutations spl, altering eye development, and AxE2, affecting wing and sensilla development, are modified by mutations at Delta. It is shown that two allele-specific suppressors of spl involve single amino acid substitutions in the 4th (Dlsup5) and 9th (Dlsup4) EGF-like elements of the Delta protein. Cultured cells producing spl or AxE2 aggregate with cells producing wild type Delta or Dlsup5 protein, and Dlsup5-producing cells adhere to cells producing wild-type Notch protein. However, spl,AxE2, and Dlsup5 are each defective in promoting these cell affinities, as none of the mutant proteins can compete with the corresponding wild-type proteins for formation of cell aggregates. Thus, widely separated EGF-like elements of Notch and Delta appear to participate in functional molecular interactions between the proteins. Dlsup5 does not improve adhesiveness of spl in vitro, so suppression in vivo may involve altered developmental signaling by spl-Dlsup5 complexes, rather than modified cell adhesion. PMID- 1419000 TI - Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs. AB - The subunit stoichiometry of the mammalian K+ channel KV1.1 (RCK1) was examined by linking together the coding sequences of 2-5 K+ channel subunits in a single open reading frame and tagging the expression of individual subunits with a mutation (Y379K or Y379R) that altered the sensitivity of the channel to block by external tetraethylammonium ion. Two lines of evidence argue that these constructs lead to K+ channel expression only through the formation of functional tetramers. First, currents expressed by tetrameric constructs containing a single mutant subunit have a sensitivity to tetraethylammonium that is well fitted by a single site binding isotherm. Second, a mutant subunit (Y379K) that expresses only as part of a heteromultimer contributes to the expression of functional channels when coexpressed with a trimeric construct but not a tetrameric construct. PMID- 1419001 TI - The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. AB - In CNS synapses, the synaptic junctional complex with associated postsynaptic density is presumed to contain proteins responsible for adhesion between pre- and postsynaptic membranes and for postsynaptic signal transduction. We have found that a prominent, brain-specific protein (PSD-95) enriched in the postsynaptic density fraction from rat brain is highly similar to the Drosophila lethal(1)discs-large-1 (dlg) tumor suppressor protein. The dlg protein is associated with septate junctions in developing flies and contains a guanylate kinase domain that is required for normal control of cell division. The sequence similarity between dlg and PSD-95 suggests that molecular mechanisms critical for growth control in developing organisms may also regulate synapse formation, stabilization, or function in the adult brain. PMID- 1419002 TI - Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice. AB - SV40 T antigen (Tag) expression directed to cerebellar Purkinje cells resulted in the generation of three transgenic mouse lines that displayed ataxia, a neurological phenotype characteristic of cerebellar dysfunction. Onset of symptoms and cerebellar pathology, characterized by specific Purkinje cell degeneration, appeared to be directly dependent upon transgene copy number. The SV5 line (containing > 30 transgene copies), exhibited embryonic transgene expression that caused selective death of immature Purkinje cells and a subsequent block in cerebellar development and ataxia at 2 weeks. The developmental effect of the disruption of Purkinje cells in SV5 mice suggests that a normal complement of these cells is required for early development of the cerebellar cortex, especially granule cell proliferation and migration from external to internal layers. Transgene expression in a second line, SV4 (10 copies), was detectable during the second postnatal week. Death of mature Purkinje cells in the SV4 line resulted in onset of ataxia at 9 weeks. Ataxia in a third line, SV6 (2 copies), was detected after 15 weeks. The distinct cerebellar phenotypes of the SV4-6 lines correlate with specific Tag-induced Purkinje cell ablation as opposed to tumorigenesis. PMID- 1419003 TI - Mechanisms underlying induction of homosynaptic long-term depression in area CA1 of the hippocampus. AB - The mechanisms responsible for long-lasting, activity-dependent decreases in synaptic efficacy are not well understood. We have examined the initial steps required for the induction of long-term depression (LTD) in CA1 pyramidal cells by repetitive low frequency (1 Hz) synaptic stimulation. This form of LTD was synapse specific, was saturable, and required activation of post-synaptic NMDA receptors. Loading CA1 cells with the Ca2+ chelator BAPTA prevented LTD, whereas lowering extracellular Ca2+ resulted in the induction of LTD by stimulation that previously elicited long-term potentiation. Following LTD, synaptic strength could be increased to its original maximal level, indicating that LTD is reversible and not due to deterioration of individual synapses. Induction of homosynaptic LTD therefore requires an NMDA receptor-dependent change in postsynaptic Ca2+ which may be distinct from that required for long-term potentiation. PMID- 1419004 TI - Responses of retinal axons in vivo and in vitro to position-encoding molecules in the embryonic superior colliculus. AB - We show that rat retinal ganglion cell axons exhibit no topographic specificity in growth along the rostral-caudal axis of the embryonic superior colliculus (SC). Position-related, morphological differences are not found between temporal and nasal axon growth cones. However, embryonic retinal axons respond in vitro to a position-dependent molecular property of SC membranes. In vivo, regional specificity in side branching is the earliest indication that axons make topographic distinctions along the rostral-caudal SC axis. Our contrasting in vivo and in vitro results indicate that molecules encoding rostral-caudal position in the SC neither guide nor restrict retinal axon growth, but may promote the development of topographic connections by controlling specificity in the extension or stabilization of branches. PMID- 1419005 TI - Was Einthoven a 21st century visionary? PMID- 1419006 TI - Effects of three anesthetic induction techniques on heart rate variability. AB - STUDY OBJECTIVE: To investigate the effects of different clinical induction techniques on heart rate variability (HRV). DESIGN: Two studies are reported. Study 1 prospectively compared the effects of two induction techniques (etomidate vs. thiopental sodium) known to have widely disparate effects on cardiovascular reflexes. Study 2 specifically investigated whether the vagotonic effects of sufentanil cause an increase in vagally mediated HRV. SETTING: Elective surgery in a university-affiliated hospital. PATIENTS: Study 1: 18 ASA physical status I patients having minor surgery; Study 2: 10 ASA physical status III and IV patients having cardiac surgery. INTERVENTIONS: In Study 1, anesthesia was induced with either etomidate 0.3 mg/kg or thiopental sodium 4 mg/kg with 60% nitrous oxide in oxygen. In Study 2, anesthesia was induced with a sufentanil infusion (total dose 2.9 +/- 0.2 micrograms/kg). MEASUREMENTS AND MAIN RESULTS: The electrocardiogram-derived heart rate signal was subjected to power spectral analysis (similar to electroencephalographic analysis) to obtain measurements of (1) absolute HRV power [units of (beats per minute)2] within defined frequency ranges (HRVLO = power between 0 and 0.125 Hz; HRVHI = power between 0.126 and 0.5 Hz; HRVTOT = HRVLO + HRVHI) and (2) normalized HRV power (the percentage of total power) within these same frequency ranges [e.g., %HRVHI = (HRVHI/HRVTOT) x 100%]. In Study 1, both techniques caused large reductions in HRVTOT. The reduction caused by the thiopental sodium technique (-89% +/- 2%) significantly exceeded that caused by the etomidate technique (-58% +/- 13%, p less than 0.02). In Study 2, sufentanil decreased absolute power measurements of vagally mediated HRV (-69 +/- 12 change in HRVHI) but increased corresponding normalized measurements of vagally mediated HRV (90% +/- 30% increase in %HRVHI). CONCLUSIONS: In Study 1, the greater reduction in HRV with the thiopental sodium technique provides evidence that the depressant effects of anesthetics on HRV are related in part to their effects on cardiovascular reflexes. However, the significant depression in HRV caused by the etomidate technique suggests that mechanisms other than baroreflex depression (e.g., impaired consciousness) also are important in these depressant effects. In Study 2, the decrease in HRVHI caused by sufentanil documents that absolute power measurements of vagally mediated HRV are not correlated with changes in parasympathetic tone during a potent opioid induction. This lack of a correlation may result from the decrease in total HRV observed with loss of consciousness. The increase in %HRVHI suggests that normalized measurements of HRV may still provide an index of changes in sympathetic parasympathetic balance, even when total HRV is decreased following anesthetic administration. PMID- 1419007 TI - Epidural opioids during laminectomy surgery for postoperative pain. AB - STUDY OBJECTIVE: To determine whether morphine applied directly to the dura during laminectomy surgery provides superior postoperative analgesia during the first 24 hours. DESIGN: Randomized, double-blind study. SETTING: A university affiliated hospital. PATIENTS: Twenty ASA physical status I and II patients ages 18 to 60 years. INTERVENTIONS: Simultaneous topical dural application and intramuscular (IM) injection of unknown solutions of saline and morphine 3 mg. MEASUREMENTS AND MAIN RESULTS: Postoperative analgesia was assessed using the visual analog scale (VAS), a modified McGill-Melzack pain questionnaire, subjective nursing evaluations, and the amount of supplemental analgesic medication used. Patients were observed for complications and side effects. Compared with the patients who received epidural saline and IM morphine, the patients who received epidural morphine and IM saline had less postoperative pain as determined by VAS scores, nursing evaluations, and amount of supplemental opioid analgesic doses (1.6 +/- 1.2 vs. 4.1 +/- 1.2 analgesic doses per patient; p less than 0.05) required in the first 24 hours. Minor side effects were similar for the two groups. No patient developed respiratory depression. CONCLUSIONS: Morphine 3 mg applied topically to the dura at the end of laminectomy surgery is a simple, safe, and effective way of providing improved postoperative analgesia. PMID- 1419008 TI - Fentanyl-induced muscle rigidity as affected by pretreatment with amantadine hydrochloride. AB - STUDY OBJECTIVE: To determine whether the degree of muscle rigidity in humans caused by the administration of high-dose fentanyl is affected by pretreatment with amantadine hydrochloride, a drug that stimulates the release of dopamine in the basal ganglia. DESIGN: Randomized, observer-blinded comparison of regimes. SETTING: Inpatient surgery at a university-affiliated teaching hospital. PATIENTS: Sixteen patients scheduled for elective surgery in whom the administration of high-dose fentanyl was felt to be appropriate. INTERVENTIONS: Eight patients in the control group were given diazepam 5 mg orally 1 hour prior to induction of anesthesia. Eight patients in an experimental group were given the same dose of diazepam and also were treated with amantadine 1 g orally in divided doses over a period of 25 hours prior to their scheduled surgery. At the time of surgery, all patients were given fentanyl 50 micrograms/kg intravenously at a rate of 1 mg/min and were clinically evaluated for the degree of muscle rigidity of the chest wall, abdomen, and extremities. MEASUREMENTS AND MAIN RESULTS: A single observer, blinded to the technique, evaluated and recorded the degree of muscle rigidity present in the chest wall, abdomen, and upper extremities immediately after administration of the fentanyl and 3 minutes later. The observer was the same individual in all instances. In no case did the muscle rigidity compromise our ability to adequately oxygenate the patient. CONCLUSIONS: Muscle rigidity associated with the administration of high-dose fentanyl is not attenuated by prior administration of amantadine in the dose range studied. PMID- 1419009 TI - The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief. AB - STUDY OBJECTIVE: To examine the efficacy of intramuscular (IM) ketorolac used in combination with intravenous (IV) patient-controlled analgesia (PCA) morphine for postoperative pain relief following intra-abdominal gynecologic surgery. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Patient care unit at a university medical center. PATIENTS: Thirty-five healthy women undergoing intra abdominal gynecologic surgery who requested postoperative PCA. INTERVENTIONS: Postoperatively, all patients received IV PCA morphine, with the PCA device programmed to deliver a maximum of 1 mg every 6 minutes (maximum of 30 mg over 4 hours). In addition, patients received one of three regimens: (1) IM saline every 6 hours; (2) IM ketorolac 30 mg while in the postanesthesia care unit (PACU), followed by 15 mg every 6 hours; or (3) IM ketorolac 60 mg while in the PACU, followed by 30 mg every 6 hours. MEASUREMENTS AND MAIN RESULTS: Patients were assessed at regular intervals. Visual analog scale (VAS) scores were used to assess analgesia and patient satisfaction with therapy. Data on morphine usage were obtained from the PCA device, and the frequency and severity of adverse effects were assessed for the presence or absence of side effects. Cumulative morphine dosages were lower (p less than 0.05) in both ketorolac groups at 12, 18, and 24 hours. VAS scores and the frequency of side effects did not differ significantly among groups. CONCLUSIONS: IM ketorolac significantly decreased PCA morphine requirements. The analgesic effects of the two drugs appear to be additive. PMID- 1419010 TI - Alkalinization of mepivacaine does not alter onset of caudal anesthesia. AB - STUDY OBJECTIVE: To determine the effect of alkalinization of mepivacaine on onset of caudal anesthesia. DESIGN: Randomized, blind study. SETTING: Colon Rectal Surgery Service of the Tertiary Center at Cleveland Clinic Foundation. PATIENTS: Young, healthy adults undergoing anal surgery. INTERVENTIONS: Addition of bicarbonate (study group) or saline (control group) to mepivacaine. MEASUREMENTS AND MAIN RESULTS: At the onset of sacral anesthesia, demographics were measured. A slightly faster onset was found in the study group (4.28 vs. 6.08 minutes), but this was not statistically significant. CONCLUSIONS: Alkalinization of mepivacaine does not significantly accelerate the onset of caudal anesthesia. PMID- 1419011 TI - Anesthesia rebreathing bags: physical characteristics and use as portable oxygen reservoirs. AB - STUDY OBJECTIVE: To examine the physical characteristics of 3-liter anesthesia rebreathing bags and assess their use for oxygen (O2) storage and delivery during transport of patients from the operating room (OR) to the recovery area. SETTING: Anesthesia laboratory and pulmonary function laboratory. INTERVENTIONS: Five anesthesia rebreathing bags were inflated in 2-liter increments with 50 liters of air and then deflated in 2-liter increments. A sixth bag was inflated twice in 1 liter increments. Five bags were inflated with 60 liters of gas and allowed to deflate through a cannula functioning as a flow restrictor. Five bags were inflated with 100 liters of gas and checked for damage. MEASUREMENTS AND MAIN RESULTS: Pressure measurements done at 2-liter increments during inflation of the bags to 50 liters and deflation showed a consistent pattern of pressure-volume relationships. Assessment of gas flow during deflation through the cannula showed flow rates ranging from 3.1 to 3.8 L/min after 5 minutes of continuous flow and from 2.8 to 3.8 L/min after 10 minutes. No weakness or damage was apparent in bags inflated with 100 liters of gas. CONCLUSIONS: It is feasible for anesthesia rebreathing bags distended with O2 to serve as lightweight, inexpensive, and easily monitored alternatives to O2 tanks for O2 delivery during transport of patients from the OR to the recovery area. PMID- 1419012 TI - Examination of the hypopharynx predicts ease of laryngoscopic visualization and subsequent intubation: a prospective study of 665 patients. AB - STUDY OBJECTIVE: To determine (a) whether the ability to visualize a patient's airway preoperatively correlates with the ability to visualize his or her larynx during laryngoscopy and (b) whether the presence of certain anatomic characteristics allows anesthetists to predict difficult laryngoscopic visualization and intubation. DESIGN: Observational. Patients were categorized into two groups: those who had one or more physical characteristics to alert an anesthetist to the possibility of difficult intubation (obesity, overbite, short neck, or decreased neck/jaw mobility) and those with none of these characteristics. SETTING: University-affiliated hospital. PATIENTS: Six hundred sixty-five patients scheduled for general anesthesia and requiring endotracheal intubation. Patients were between the ages of 18 and 88 years, with body weight ranging from 21 kg to 141 kg. INTERVENTIONS: Preoperatively, the anesthetist obtained the best view of the hypopharynx by having the patient extend the tongue and phonate. The airway was then categorized into one of three classes by the ability to see the tonsillar pillars and uvula (Class A, best view--all four tonsillar pillars and uvula seen; Class B, part of the pillars and uvula seen; Class C, worst view--pillars not seen and uvula partially or not seen). After induction, the same anesthetist graded laryngeal visibility into one of four groups depending on his ability to see the patient's epiglottis and vocal cords. MEASUREMENTS AND MAIN RESULTS: Patients with one or more clinical clues were more likely to have poor visualization of the hypopharynx and, in turn, poor laryngoscopic visualization of the glottis. Patients who had a Class A airway tended to have easy laryngoscopic visualization and were relatively easy to intubate. Conversely, patients with no clinical clues and a Class C airway had poor glottic exposure. CONCLUSIONS: Our study confirms work showing that the ability to visualize structures of the hypopharynx is a good predictor of subsequent glottic visualization during laryngoscopy and of ease of intubation. PMID- 1419013 TI - Hemodynamic and respiratory effects of transtracheal high-frequency jet ventilation during difficult intubation. AB - STUDY OBJECTIVE: To evaluate the hemodynamic and respiratory effects of percutaneous transtracheal high-frequency jet ventilation (HFJV) during difficult intubation using fiberoptic bronchoscopy under general anesthesia. DESIGN: Prospective study. SETTING: Surgical patients scheduled for general anesthesia at the Medical College of Virginia Hospital. PATIENTS: Eight patients with known difficult airways. Three patients had deformed facial structures. One patient had temporomandibular joint impairment. Four patients had tumors of the oral cavity with deformed upper airways. INTERVENTIONS: A 13-gauge cricothyroidotomy jet ventilation cannula was inserted percutaneously under local anesthesia. Anesthesia was induced with etomidate 0.2 to 0.3 mg/kg, alfentanil 15 to 20 micrograms/kg, and vecuronium 0.1 mg/kg. HFJV was started with 100% oxygen at 30 to 35 pounds per square inch of driving pressure, 100 cycles per minute, and an inspiratory/expiratory ratio of 25%. Thoracic electrical bioimpedance was used to measure cardiac index (CI) and ejection fraction (EF). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP), heart rate (HR), CI, and EF were measured before induction of anesthesia; after 1 minute of HFJV, 5 minutes of HFJV, and 10 minutes of HFJV; and during positive pressure ventilation following fiberoptic intubation. Arterial blood gas samples were obtained before induction of anesthesia and after 10 minutes of HFJV. HR decreased significantly after 5 minutes of HFJV, after 10 minutes of HFJV, and after intubation (p less than 0.05). MAP decreased significantly after 10 minutes of HFJV compared with the preinduction value (mean, 97 to 71 mmHg; p less than 0.01). Although EF increased significantly following intubation, from 46% to 59%, there were no significant changes in CI. Arterial oxygen tension increased from 85 to 240 mmHg (p less than 0.05). Arterial carbon dioxide tension also increased, from 39 to 42 mmHg (p less than 0.05). CONCLUSIONS: Transtracheal HFJV under general anesthesia with etomidate, alfentanil, and vecuronium provided satisfactory hemodynamic conditions and pulmonary gas exchange. Percutaneous transtracheal HFJV can be used safely to manage patients with a difficult airway under general anesthesia using fiberoptic bronchoscopy. PMID- 1419014 TI - Lidocaine blood levels following aerosolization and intravenous administration. AB - STUDY OBJECTIVE: To determine whether, following aerosolization of lidocaine for topical airway anesthesia, intravenous (IV) lidocaine produces toxic lidocaine blood concentrations. DESIGN: Randomized, double-blind study. SETTING: University affiliated hospital. PATIENTS: Forty healthy patients scheduled for outpatient surgery. INTERVENTIONS: The patients received in a randomized, double-blind manner aerosolized lidocaine or placebo followed 10 minutes later by IV lidocaine or placebo. MEASUREMENTS AND MAIN RESULTS: After completion of lidocaine or placebo aerosolization and 2 minutes following IV administration of either lidocaine or the placebo, venous blood samples were obtained. Lidocaine concentration was measured using a homogenous enzyme assay. The group receiving both aerosolized and IV placebo and the group receiving aerosolized lidocaine and an IV placebo had undetectable (less than 0.05 micrograms/ml) serum lidocaine levels. The groups that received either an aerosolized placebo or aerosolized lidocaine and IV lidocaine had similar serum lidocaine concentrations [3.34 +/- 0.46 vs. 3.24 +/- 0.55 micrograms/ml (mean +/- SEM); p greater than 0.05 by Mann Whitney U test]. CONCLUSION: IV lidocaine can be safely administered following aerosolization of lidocaine in spontaneously breathing patients without producing toxic blood lidocaine concentrations. PMID- 1419015 TI - Excessive atlanto-occipital flexion as a cause of complete airway obstruction following anterior cervical spine fusion. AB - This report describes complete airway obstruction following anterior cervical fusion caused by extreme, fixed flexion of the neck in a halo device. The causes and treatment of such an airway complication are reviewed. PMID- 1419016 TI - Should supraclavicular brachial plexus block be avoided in pregnancy? AB - Unilateral phrenic nerve block is common after supraclavicular brachial plexus block techniques, although it is rarely symptomatic in patients without respiratory disease. A 24-weeks-pregnant woman was scheduled for a carpal tunnel release because of intractable pain. After a perivascular subclavian brachial plexus block with 30 ml of 0.33% plain bupivacaine was performed, the patient developed a right phrenic nerve block manifested by acute dyspnea and cough. No deleterious consequences followed, but surgery was canceled. Respiratory changes produced by pregnancy might compromise ventilatory reserve. Thus, we suggest avoiding supraclavicular approaches to brachial plexus block in pregnant women, since they may be as prone to developing respiratory embarrassment, secondary to phrenic block, as patients with pulmonary pathology. PMID- 1419017 TI - Postoperative elevation of serum transaminases following isoflurane anesthesia. AB - Halogenated inhalational anesthetics have been implicated in hepatotoxicity. Halothane hepatitis results from the biotransformation of the drug to a metabolite that binds to liver proteins, which creates a hapten, which, in turn, causes an immunologic response in the liver. Case reports of hepatic injury resulting from isoflurane, which has a decreased biotransformation compared with that of halothane, have received much criticism. We describe a patient who had elevated liver enzymes and a positive trifluoroacetyl antibody titer following an anesthetic regimen that included isoflurane. PMID- 1419018 TI - A simple device for transtracheal ventilation. PMID- 1419019 TI - The human immunodeficiency virus: knowledge and precautions among anesthesiology personnel. PMID- 1419020 TI - Frequency of anesthetic cardiac arrest in infants: effect of pediatric anesthesiologists. PMID- 1419021 TI - Postintubation croup in children. PMID- 1419022 TI - Urinary drainage bag distention: an indication of bladder injury during laparoscopy. PMID- 1419023 TI - Reporting every look-alike is no longer novel: similarities between labels are a fact of life. PMID- 1419024 TI - We don't treat air embolism in plastic models. PMID- 1419025 TI - Endothelin-1 and endothelin-3 induce chemotaxis and replication of pulmonary artery fibroblasts. AB - The remodeling of pulmonary vessels that occurs in association with pulmonary hypertension involves, in part, thickening of the adventitia. The stimulus for this process is not understood. One explanation is that endothelial cells secrete a growth factor that expands the local population of fibroblasts by acting as a chemoattractant and mitogen. Endothelins are a family of potent newly discovered vasoactive peptides. One of these compounds, endothelin-1 (ET-1), is secreted by endothelial cells and is known to constrict pulmonary vessels. Another, endothelin-3 (ET-3), is not secreted by endothelial cells and is less potent as a pulmonary vasoconstrictor. We hypothesized that the endothelins may have the capacity both to constrict these vessels and to initiate fibroblast chemotaxis and replication. Here we investigated the effects of both ET-1 and ET-3 on the chemotaxis and replication of fibroblasts derived from pulmonary vessels. Cells were isolated from rat pulmonary arteries, cultured in medium and 10% newborn calf serum, and used between passages 2 and 5. Chemotaxis was assessed using a modified Boyden chamber with a polycarbonate filter (pore size, 8 microns) separating cells in the upper chambers from endothelin in the lower chambers. Replication was assessed both by direct cell counts and by a colorimetric assay based on uptake and subsequent release of methylene blue. Both ET-1 and ET-3 induced chemotaxis of pulmonary artery fibroblasts and did so in a dose-dependent fashion. The maxima for both peptides occurred at a concentration of about 10(-7) M, when chemotaxis was greatest for ET-1 (22 +/- 1.4 versus 14 +/- 1.8 cells/grid [mean +/- SEM], (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419026 TI - Modulation of ion transport in cultured rabbit tracheal epithelium by lipoxygenase metabolites. AB - Lipoxygenase metabolites influence ion movement and fluid balance in the airways. We studied the effects of nordihydroguaiaretic acid (NDGA), a general inhibitor of the lipoxygenase pathway, on Na+ and Cl- secretion in cultured tracheal epithelial cells from adult rabbits through short-circuit current (Isc) and radioactive tracer flux experiments. NDGA inhibition of leukotriene release in freshly isolated rabbit tracheal epithelial cells was assayed by a 3H peptidyl leukotriene radioimmunoassay. 3 microM NDGA resulted in a 91% reduction of leukotriene release. In unstimulated cultures, Cl- secretion (furosemide inhibited fraction of Isc) was 11.1 +/- 2.8 muamp/cm2 (n = 10) and was unchanged in the presence of NDGA (n = 10). Epinephrine-stimulated Cl- secretion increased Isc by 12.2 +/- 2 muamp/cm2 (n = 10). This stimulation was unchanged by pretreatment with NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway did not affect Cl- secretion. In unstimulated cultures, Na+ absorption (amiloride-inhibited portion of Isc) was 10.7 +/- 3.3. muamp/cm2 (n = 10) and was reduced by 79% in the presence of NDGA (n = 10), suggesting that inhibition of the lipoxygenase pathway was associated with inhibition of Na+ absorption. Radioactive tracer flux experiments supported these findings. Exogenous LTD4 (n = 7) and LTC4 (n = 7) were added to cells pretreated with NDGA, and Na+ absorption was restored to 76% and 70% of control, respectively. In addition, LTD4 (n = 4) and LTC4 (n = 4) were added to cells without prior inhibition of the lipoxygenase pathway to NDGA and resulted in an increase in Cl- secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419027 TI - Effect of ozone on platelet-activating factor production in phorbol differentiated HL60 cells, a human bronchial epithelial cell line (BEAS S6), and primary human bronchial epithelial cells. AB - Platelet-activating factor (PAF) is a phospholipid with a wide spectrum of pro inflammatory properties. In the lung, PAF induces airway hyperresponsiveness, neutrophil sequestration, and increased vascular permeability. The alveolar macrophage and the bronchial epithelium are tissues that are exposed to inhaled ozone (O3). We studied the effect of an in vitro O3 exposure on PAF production in a macrophage-like HL60 human cell line (dHL60), a human bronchial epithelial cell line (BEAS S6), and also in primary human bronchial epithelial cells. PAF was quantified by thin-layer chromatographic separation of lipid extracts from cells radiolabeled with [3H]lysoPAF and by radioimmunoassay. In vitro exposure of dHL60 cells to 0.05 to 1.0 ppm O3 for 15 to 120 min was found to significantly increase PAF levels above air control values at all exposure levels and time points (average increase of 92%). Similarly, BEAS S6 cells grown on collagen-coated filter supports and exposed to 0.05 to 1.0 ppm O3 for 60 min released an average increase in PAF of 626% above control values. Primary human bronchial epithelial cells also demonstrated significant increases in [3H]PAF release (average increase of 289% after exposure to 1.0 ppm O3 for 60 min) compared with paired air controls. These findings suggest that some of the effects of O3 inhalation may be mediated by PAF. PMID- 1419028 TI - Cloning of T lymphocytes from bronchoalveolar lavage fluid. AB - We have prepared T-cell clones from bronchoalveolar lavage fluid (BALF) from four healthy, nonsmoking persons and from four patients with allergic asthma. T cells were cloned by direct limiting dilution and with the use of a fluorescent activated cell sorter with an automated cell deposition unit. T-cell clones from the blood (PB) were prepared as well. The cloning efficiencies of T cells from BALF ranged from 3 to 40% and were lower than those obtained from PB T cells (18 to 72%). The cloning conditions generated CD4+ as well as CD8+ clones. The very late antigen-4, VLA-4, was more frequently expressed on CD4+ T-cell clones from BALF than from the blood (P < 0.05). CD8+ clones from BALF were more frequently VLA-1+ than those from blood (P < < 0.01). Mitogen- and monoclonal antibody driven proliferation of CD4+ clones showed that BALF clones were well responsive to proliferation stimuli similar to those from the blood. Analysis of interleukin 4 production by 10 BALF and 10 PB clones showed large variations between individual CD4+ clones (BALF: range, < 100 to 700 pg/ml; PB: range, < 100 to 1,100 pg/ml), indicating the generation of different types of clones, which was also clear from analysis of interferon-gamma production. The analysis of properties of BALF T-cell clones and their regulation will improve insight into immunologic reactions in the lungs. PMID- 1419029 TI - Flow cytometric analysis of lymphocyte phenotypes in bronchoalveolar lavage fluid: comparison of a two-color technique with a standard immunoperoxidase assay. AB - Characterization of lymphocytes in bronchoalveolar fluid has provided insight into the pathogenesis of many pulmonary diseases. Identification of lymphocyte phenotypes has become highly successful due to development of specific monoclonal antibodies and reliable methods for detecting labeled cells such as flow cytometry (FCM) and immunocytochemistry. FCM permits rapid screening of many cells, but this analysis may be confounded by heterogeneity in the size and granularity of the cells being evaluated. Such heterogeneity may lead to exclusion of cells of interest and inclusion of unwanted cells. Often peripheral blood leukocytes are used to define the gate for lung lymphocytes, but this gate may be inappropriate due to considerable variation in size and granularity of cells in bronchoalveolar lavage (BAL) fluid. Here we report an alternative method for generating a gate which employed fluorescence and side scatter signals to analyze lymphocyte subsets in BAL fluid by FCM. This gating technique avoids the pitfalls inherent in using the conventional lymphocyte gate to analyze lung cells. To validate this approach, we compared the results generated by this gate and those from the conventional forward/side light scatter gate to results derived from an immunocytochemical technique (ABC) that has been extensively employed in our laboratory to identify lymphocyte subsets in blood and lavage fluid. FCM tended to underestimate the proportions of T-cell subsets compared with ABC when the conventional gate was used. Counting only cells that stained with fluorescein-conjugated anti-CD45 antibody and that had side scatter properties of lymphocytes, however, resulted in excellent agreement between FCM and ABC. It appears that the CD45+/side scatter gate includes the vast majority of lymphocytes in BAL fluid while excluding most of the nonlymphoid cells that contaminate the conventional gate. It was this latter group of cells, and erythrocytes in particular, that led to the artificially low values for lymphocyte phenotypes in BAL fluid by FCM when the conventional lymphocyte gate was used. Although erythrocytes in BAL fluid may be eliminated by hypotonic lysis, this may also result in contamination of the conventional lymphocyte gate with nuclear debris and particulates from macrophages. Despite these advantages, the fluorescence/side scatter gate may not always be optimal for the evaluation of T lymphocytes if BAL fluid contains CD45+, nonlymphoid cells with low side light scatter. In these instances, additional antibodies such as anti-CD14 and anti-CD11 may be employed to determine the size of contaminant monocytic cells and neutrophils.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1419030 TI - Increased fibronectin mRNA in alveolar macrophages following in vivo hyperoxia. AB - Oxygen-mediated lung injury can stimulate a fibroproliferative response resulting in the alteration of the pulmonary extracellular matrix and subsequent scarring of parenchymal tissue. Fibronectin (FN), a component of the extracellular matrix, appears in increased quantities in fibrotic lung disease. Alveolar macrophages (AMs) are a potential source of this molecule. Using quantitative in situ hybridization, we demonstrated that AMs from rabbits acutely exposed to 100% oxygen (hyperoxia) for up to 64 h have 20-fold greater levels of FN mRNA relative to cells from control animals. When animals were allowed to recover in room air for up to 72 h after maximal oxygen exposure, AM FN mRNA abundance approached baseline levels. Furthermore, in oxygen-exposed animals, the fraction of lavaged cells expressing FN mRNA was increased 10-fold relative to controls. Although there was marked cell-to-cell variation, we conclude that the AM is a potential source of FN in the events leading to hyperoxia-induced pulmonary fibrosis. PMID- 1419032 TI - Magnetic resonance imaging of adult intra-axial brain tumors. AB - The detection and characterization of intra-axial tumors in the adult have been greatly improved with the advent of magnetic resonance (MR) imaging, particularly when combined with paramagnetic contrast enhancement. MR imaging allows tumor localization along with evaluation of edema, tumor margins, intrinsic signal intensity on T1- and T2-weighted sequences, and the presence or absence of enhancement. Consideration of these characteristics together with pertinent clinical history forms the basis of a reasonable differential diagnosis. The article summarizes the MR imaging characteristics and pathologic findings of the major intra-axial tumors of adults with emphasis on differential considerations. PMID- 1419031 TI - The application of contrast agents in the evaluation of neoplasms of the central nervous system. AB - Magnetic resonance evaluation of central nervous system neoplasms has improved tremendously since the introduction of gadolinium-based contrast agents. The optimal application of these agents in clinical imaging, however, has not been well established. The article discusses the recent application of these agents to a number of intracranial neoplasms, including metastases, gliomas, pituitary adenomas, and acoustic neurinomas/cerebellopontine angle tumors. PMID- 1419033 TI - Adult extra-axial brain tumors. AB - Magnetic resonance imaging is the preferred cross-sectional imaging study for the evaluation of nearly all extra-axial brain tumors in adults. This article outlines the neoplasms by their pathology. The discussion covers the neoplasms originating from central neuroglial cells, meninges, and cranial nerves. In addition, developmental tumors and cysts and secondary extra-axial tumors are discussed. PMID- 1419034 TI - Pediatric primary brain tumors. AB - Magnetic resonance (MR) studies of pediatric brain tumors have been reported. Instead of reviewing previous studies, this article addresses specific subjects related to pediatric brain tumors, including MR signal characteristics, fourth ventricular tumors, pineal region tumors, tumors in chronic epilepsy, tumors in early infancy, and brain tumors in phakomatoses. PMID- 1419035 TI - Uses and limitations of spoiled gradient-refocused imaging in the evaluation of suspected intracranial tumors. AB - This article describes the use of a radiofrequency-spoiled gradient-recalled (SPGR) imaging pulse sequence in the evaluation of intracranial masses. This pulse sequence provides excellent anatomic detail with T1-weighted image contrast. Rapid, sequential, single-slice (two-dimensional) images of the brain can be obtained in patients who are unable to hold still for long periods of time. In addition, volumetric (three-dimensional) image data sets can be obtained that provide extremely thin (1- to 2-mm) sections of high detail and good signal to-noise ratio for selected critical structures within the brain. Finally, because SPGR is also utilized for time-of-flight angiography, parenchymal information can be obtained simultaneously with cerebral blood vessel definition. One potential pitfall that the magnetic resonance radiologist must be aware of is the fact that, in many patients, the degree of contrast enhancement is greatly diminished on postgadolinium SPGR images compared with conventional spin-echo T1 weighted images. Comparison with a set of standard spin-echo postcontrast images or, potentially, the use of higher doses of gadolinium may solve this problem. In spite of this limitation, the selective utilization of SPGR imaging can yield additional useful information for evaluation and preoperative planning in patients with intracranial masses. PMID- 1419036 TI - Sellar and juxtasellar neoplasms. AB - Magnetic resonance imaging is the modality of choice for evaluating lesions in and around the sella turcica. The article highlights various neoplasms of the pituitary gland and the juxtasellar region. The differentiating imaging characteristics and clinical presentations of these neoplasms are discussed. Even with the best imaging techniques available, however, biopsy or excision of the lesion is still necessary to establish the histologic diagnosis. PMID- 1419037 TI - Protein targeting to and translocation across the membrane of the endoplasmic reticulum. AB - Several approaches are currently being taken to elucidate the mechanisms and the molecular components responsible for protein targeting to and translocation across the membrane of the endoplasmic reticulum. Two experimental systems dominate the field: a biochemical system derived from mammalian exocrine pancreas, and a combined genetic and biochemical system employing the yeast, Saccharomyces cerevisiae. Results obtained in each of these systems have contributed novel, mostly non-overlapping information. Recently, much effort in the field has been dedicated to identifying membrane proteins that comprise the translocon. Membrane proteins involved in translocation have been identified both in the mammalian system, using a combination of crosslinking and reconstitution approaches, and in S. cerevisiae, by selecting for mutants in the translocation pathway. None of the membrane proteins isolated, however, appears to be homologous between the two experimental systems. In the case of the signal recognition particle, the two systems have converged, which has led to a better understanding of how proteins are targeted to the endoplasmic reticulum membrane. PMID- 1419038 TI - Mechanisms that determine the transmembrane disposition of proteins. AB - The final orientation that a protein assumes in the membrane of the endoplasmic reticulum is determined by a few types of signal sequences and their respective interactions with the membrane insertion complex. Membrane insertion occurs via a series of discrete steps, some of which are regulated by GTP- and ATP-binding proteins. Analysis of the protein components in proximity to nascent secretory and membrane proteins has revealed novel proteins in the endoplasmic reticulum that may form part of the membrane insertion complex. PMID- 1419039 TI - Genetic and biochemical analysis of vesicular traffic in yeast. AB - Secretory, vacuolar and membrane protein transport in yeast occurs by processes that are highly conserved in eukaryotic cells. Recent years have seen a proliferation of approaches to the study of vesicular traffic, and in certain instances key breakthroughs have been achieved through the application of genetic and biochemical methods that are well suited to yeast as an experimental organism. The availability of the genetic approach has led to molecular insights concerning the mechanisms of vesicle biogenesis, targeting and fusion. PMID- 1419041 TI - The endoplasmic reticulum-Golgi intermediate compartment. AB - The recent identification of an endoplasmic reticulum-Golgi intermediate compartment has added to the complexity of the structural and functional organization of the early secretory pathway. Protein sorting along the endoplasmic reticulum-Golgi pathway depends on different signals and mechanisms, some of which guarantee recycling from various levels of the Golgi apparatus to biosynthetically earlier compartments. PMID- 1419040 TI - Regulation of intracellular membrane transport. AB - A number of proteins that are necessary for membrane transport have been identified using cell-free assays and yeast genetics. Although our knowledge of transport mechanisms remains limited, common themes are clearly emerging. In particular, specific GTP-binding proteins appear to be involved, not only at all steps of membrane traffic but also at more than one check-point within each step. The ordered sequence of events occurring during vesicle formation, targeting and fusion may be regulated in a stepwise manner by specific GTP-dependent switches, which act as modular elements of the transport mechanism. PMID- 1419042 TI - Regulation of vesicular and tubular membrane traffic of the Golgi complex by coat proteins. AB - Transport of cargo through and from the Golgi complex is mediated by vesicular carriers and transient tubular connections. Two classes of vesicle have been implicated in the biosynthetic or anterograde membrane traffic of this organelle. Both classes of vesicle are coated on the cytoplasmic surface with proteins, of which at least one component is related. Tubular connections also enable exchange of material between membrane-bounded compartments associated with the Golgi complex, most obviously in cells that have been treated with the drug, brefeldin A. Coat proteins appear to be involved in the regulation of these transport processes. Their putative functions include sorting of cargo, as well as regulation of budding, fusion or targeting of the membrane carriers. PMID- 1419043 TI - Biogenesis of storage granules and vesicles. AB - The production of storage granules and vesicles that undergo regulated exocytosis occurs via biosynthetic and endocytotic pathways, respectively. Prominent in the formation of secretory granules in the Golgi apparatus is selective protein aggregation, which may account for the biogenesis of multiple granules in a single cell. New cDNA transfection and immunolocalization studies have helped to further refine our understanding of the relationship between the formation of regulated secretory vesicles and the early stages of the endocytotic pathway. Recent insights into the targeting of membrane proteins to these organelles have implicated both specific sorting signals and protein-protein aggregation. PMID- 1419044 TI - W(h)ither default? Sorting and polarization in epithelial cells. AB - The discovery of basolateral sorting signals in the past year may leave the default pathway with nowhere to go. With new results suggesting that even more GTP-binding proteins and coatamers might be involved in transport and targeting, it is clear that the age of mapmaking in polarization research is nearly over. PMID- 1419045 TI - Structure and biological effects of lipid modifications on proteins. AB - Both the prevalence of lipid modifications of proteins and their importance for protein function and cellular localization have been widely observed. The advances made during the past year in defining the enzymology of lipid addition and in understanding the biological consequences of these modifications on protein function are discussed. PMID- 1419046 TI - Putting energy into mitochondrial protein import. AB - The import of proteins into mitochondria occurs in several steps. At least three of these steps require ATP and involve molecular chaperones. This energy requirement has served as a useful tool for elucidating the import pathways into the four mitochondrial compartments. PMID- 1419047 TI - Organellar proton-ATPases. AB - Proton pumps that belong to the families of F-ATPases and V-ATPases operate without the formation of a phosphorylated intermediate and contain several subunits grouped into distinct catalytic and membrane sectors. Recent studies on the structure and molecular biology of V-ATPases shed light not only on the structure-function relations between the two families, but also on their evolution in all organisms. PMID- 1419048 TI - Determinants of the calcium permeation of ligand-gated cation channels. AB - Fast synaptic transmission in the vertebrate brain is mediated by ligand-gated channel receptors. As some of these receptors have been implicated in learning and memory, it is important to understand their mechanism of action at a molecular level. Excitatory receptors are members of large gene families of related channels that are gated by acetylcholine, serotonin, and the most abundant neurotransmitter, glutamate. Within the last year, a number of important studies have focused on the ability of these channels to flux calcium ions. Calcium entry into neurons through some of these channels triggers biochemical cascades, which can lead to changes in synaptic efficacy, presumed to be a requisite for memory formation, or if it occurs in excess, to cell death. Recent studies that attempt to determine the channel structures responsible for this calcium conductance will be discussed. PMID- 1419049 TI - Sodium-calcium exchange. AB - During the past year, significant advances have been made in the investigation of molecular, kinetic and electrophysiological aspects of Na(+)-Ca2+ exchange. The cardiac and retinal exchangers have been cloned and structure-function studies have begun. PMID- 1419050 TI - Membrane transport proteins: implications of sequence comparisons. AB - Analyses of the sequences and structures of many transport proteins that differ in substrate specificity, direction of transport and mechanism of transport suggest that they form a family of related proteins. Their sequence similarities imply a common mechanism of action. This hypothesis provides an objective basis for examining their mechanisms of action and relationships to other transporters. PMID- 1419052 TI - Membranes. PMID- 1419051 TI - Sodium cotransport proteins. AB - Significant advances have been made in elucidating the structure of Na+ cotransport proteins. Some fifteen of these low-abundance proteins have been cloned, sequenced and functionally expressed. They are members of the 12 membrane spanning superfamily and they segregate into two groups, the Na+/glucose (SGLT1) and Na+/Cl-/GABA (GAT-1) families. SGLT1 transporters are expressed in bacteria and animal cells, while GAT-1 transporters are mostly expressed in the brain. None have yet been found in plants. PMID- 1419053 TI - Membrane permeability. PMID- 1419054 TI - Structure, function and evolutionary relationship of proteins containing a disintegrin domain. AB - Disintegrins are soluble integrin ligands from snake venoms that disrupt cell matrix interactions. Recently, the nuclear magnetic resonance structures of two disintegrins were determined, providing provocative molecular insight into how a disintegrin may engage an integrin. In addition, it has recently been realized that disintegrins are derived from larger multifunctional proteins, and that there is a family of membrane-anchored, disintegrin domain-containing proteins that may promote important cell-cell interactions. PMID- 1419055 TI - Inside-out integrin signalling. AB - Integrins are expressed by virtually all cells and play key roles in a range of cellular processes. Changes in the integrin surface repertoire provide a means of altering the strength and ligand preferences of cell adhesion. Recent research has examined the affinity modulation of integrins, a rapid and versatile mechanism of cell adhesion regulation. Studies with a prototype, alpha IIb beta 3, indicate that intracellular events influence the conformation and ligand binding affinity of the extracellular domain of integrins. This 'inside-out' signal transduction appears to be mediated through the integrin cytoplasmic domains. In addition, in some cases affinity modulation of integrins may be cell type specific. The clarification of the mechanisms of integrin affinity modulation should help explain rapid changes in cell adhesion that occur during cell migration, aggregation and the cell cycle. PMID- 1419056 TI - The role of proteoglycans in cell adhesion, migration and proliferation. AB - Proteoglycans comprise a part of the extracellular matrix that participates in the molecular events that regulate cell adhesion, migration and proliferation. Their structural diversity and tissue distribution suggest a functional versatility not generally encountered for other extracellular matrix components. This versatility is mainly dictated by their molecular interactions and their ability to regulate the activity of key molecules involved in several biological events. This molecular cooperativity either promotes or inhibits cell adhesion, migration and proliferation. A growing number of studies indicate that proteoglycans can play a direct role in these cellular events by functioning either as receptors or as ligands for molecules that are required for these events to occur. Such studies support a role for proteoglycans as important effectors of cellular processes that constitute the basis of development and disease. PMID- 1419058 TI - Assembly of extracellular matrix. AB - A great challenge in understanding how different extracellular matrices assemble is to sort through the vast number of possible interactions between and among matrix molecules. The most profound insights are likely to come from patients with defined defects of matrix molecules and the use of transgenic mice or other experimental technologies that mimic the complexity of the human system. PMID- 1419057 TI - Membrane proteases: roles in tissue remodeling and tumour invasion. AB - The coordinated control of extracellular matrix degradation on the cell surface involves three crucial elements: secreted proteases and their inhibitors, surface protease receptors and integral membrane proteases. The roles that each of these elements play in cell surface proteolysis are described. The localization of proteases to the cell surface, protease activation, and regulation of cell surface proteolysis by protease inhibitors are key issues for elucidating the role of membrane proteases in tissue remodeling and tumour invasion. PMID- 1419059 TI - Functional domains of cell adhesion molecules. AB - A number of molecules involved in cell adhesion (e.g. fibronectin, laminin, collagens I and IV, thrombospondin, entactin) have now been identified and the consequent roles that they play in the processes of growth, migration, differentiation and tumor spread have been described. Active sequences of the molecules have been identified using synthetic peptides derived from specific domains. Several adhesive molecules contain multiple active domains with different biological activities. PMID- 1419060 TI - Adhesion cascades: diversity through combinatorial strategies. AB - Cell adhesion occurs via a highly regulated set of sequential interactions. Prototypic components of a variety of adhesion cascades are discussed, including integrins, triggering molecules and lectin-carbohydrate interactions. Selectivity and efficiency are achieved by utilizing the right combination of multiple adhesion molecules and by their coordinated biochemical regulation. PMID- 1419061 TI - Endothelial cells: adhesion and tight junctions. AB - This article reviews recent discoveries concerning the identity of endothelial cell adhesion molecules and their participation in intercellular junction formation. Observations relating to the formation of high-resistance tight junctions between brain endothelial cells are emphasized. PMID- 1419062 TI - Molecular linkage between cadherins and actin filaments in cell-cell adherens junctions. AB - The cell-cell adherens junction is a site for cadherin-mediated cell adhesion where actin filaments are densely associated with the plasma membrane through its well-developed plasmalemmal undercoat. Recent research has focused on the molecular linkage between cadherins and actin filaments in the undercoat of adherens junctions in order to understand the functions of these undercoat constitutive proteins in the regulation and signal transduction of cadherin-based cell adhesion. PMID- 1419063 TI - Leukocyte-endothelial cell interactions. AB - The movement of leukocytes from the blood circulation into organized lymphoid tissues or sites of inflammation requires cooperative interactions between signaling and adhesion molecules. Selectins mediate the initial rolling contacts of leukocytes with the endothelium. Following leukocyte activation, integrins strengthen adhesion and then direct migration beneath the endothelium. Unique combinations of signaling and adhesion molecules may regulate the subsets of leukocytes that are recruited into specific tissues. PMID- 1419064 TI - Regulation of cartilage and bone differentiation by bone morphogenetic proteins. AB - Quantum advances have recently been made in the understanding of the regulation of cartilage and bone differentiation through the identification, purification, genetic cloning and expression of recombinant bone morphogenetic proteins. Bone morphogenetic proteins are a family of pleiotropic differentiation factors with actions on chemotaxis, mitosis, initiation and promotion of chondrogenic and osteogenic phenotypes. They bind extracellular matrix components, heparin and type IV collagen and initiate bone repair. The cascade of cartilage and bone differentiation consists of several continuous phases: initiation, promotion, maintenance and termination. PMID- 1419065 TI - Synthesis, assembly and function of plant cell wall macromolecules. AB - The plant cell wall consists of a structurally intricate network of polysaccharide and protein whose biosynthesis, assembly and functions are still poorly understood. Recent research has shown how cell wall macromolecules, and fragments thereof, appear to be involved in processes such as cell growth, cell and tissue differentiation and the control of pathogenesis. PMID- 1419066 TI - Modulators of neuronal migration and neurite growth. AB - A multitude of molecules have been identified over the past few years that promote neurite outgrowth in vitro. The concept that these molecules work mainly by providing an adhesive surface for neuronal growth cones has been challenged by evidence from recent experiments. Some of the substrate molecules have diverse actions on cell migration and neurite growth. In addition, there is now evidence that there are molecules that specifically inhibit growth cone locomotion. This has given rise to the hypothesis that growth cones integrate a variety of growth promoting and inhibitory signals and translate them into directed locomotion. PMID- 1419067 TI - Cell-to-cell contact and extracellular matrix. PMID- 1419068 TI - Fibroblast growth factor-stimulated phosphorylation of a lipocortin I-like protein is S-phase cell cycle specific in human vascular endothelial cells. AB - We examined whether the phosphorylation of a 34 kDa lipocortin I-like protein may be associated with internalization process of fibroblast growth factor (FGF) in human umbilical vein endothelial (HUVE) cells. We show that: 1) exposure of synchronized HUVE cells to basic FGF for an appreciable time lag (> or = 30 min) at 37 degrees C and subsequent phosphorylation at 37 degrees C are required to obtain an increased 32P-labelling of a 34 kDa substrate; 2) this FGF-stimulated phosphorylation occurs in S phase but not G1 phase of the growth cycle; 3) the 34 kDa substrate appears to be phosphorylated on tyrosine residues; 4) a major fraction of the 34 kDa 32P-labelled substrate is immunoprecipitated with an antibody that has been raised against human lipocortin/annexin of type I. It is suggested that internalized FGF-receptor/kinase complexes might be primarily responsible for the phosphorylation of the 34 kDa lipocortin I-related protein in S phase HUVE cells. PMID- 1419069 TI - Intermolecular cystine-bonding of murine interleukin 2 indicates that ligand dimerization is important for the formation of the high-affinity receptor complex. AB - Interleukin 2 is thought to be active as a monomeric protein. As the nonessential Cys-140 of murine interleukin 2 (mIL2) is located in the hydrophobic interface of the amphiphilic F domain it was successfully used to stabilize hydrophobic amino acid contacts between two mIL2 cores yielding biologically active cystine-bonded dimeric mIL2. (3H) thymidine incorporation assays with intermolecular cystine bonded or monomeric mIL2 revealed almost identical median effective concentrations (EC50) and high-affinity dissociation constants (Kdh), respectively. Comparative binding and internalization assays suggest that one cystine-bonded dimeric or two monomeric mIL2 molecules bind to the high-affinity receptor complex. Furthermore, DSS concentration-dependent crosslinking studies using monomeric mIL2 revealed four membrane-derived protein-complexes with apparent molecular weights of about 70 kDa, 85 kDa, 95 kDa and 100 kDa, respectively, showing that both mIL2 receptor chains may be crosslinked to a monomeric or dimeric ligand molecule, respectively. We therefore propose that dimerization of murine interleukin 2 occurring either in solution at concentrations above the low-affinity dissociation constant or at the low affinity receptor is important for regulation of high-affinity complex formation and signal transduction. PMID- 1419070 TI - High levels of biologically active vascular endothelial growth factor (VEGF) are produced by the baculovirus expression system. AB - Vascular endothelial growth factor (VEGF) is a recently discovered mitogen for endothelial cells in vitro, and a potent angiogenesis promoting factor in vivo. VEGF is secreted from producing cells as a homodimer, binds to specific receptors on the cell surface of endothelial cells, and is produced in four forms as a result of alternative splicing. We have expressed the cDNA encoding the 165 amino acid long isoform of VEGF in insect cells using the baculovirus based expression vector. We show that infected insect cells secrete large amounts of VEGF. Antibodies directed against a synthetic peptide prepared from human VEGF identify the secreted factor. The baculovirus derived VEGF expressed in insect cells (inVEGF) binds directly to the VEGF receptors inVEGF competes with pure mammalian cells derived [125I]-VEGF for binding to the VEGF receptors that are present on the cell surface of endothelial cells. Furthermore, inVEGF is biologically active and induces the proliferation of human umbilical vein derived endothelial cells. PMID- 1419071 TI - Expression and characterization of bone morphogenetic protein-2 in Chinese hamster ovary cells. AB - Bone is a dynamic tissue that responds to many factors including vitamin D, parathyroid hormone, estrogen, calcitonin, and bone morphogenetic proteins (BMPs). The ability to stimulate new bone growth would permit novel therapies for situations where bone mass has been lost due to accident or disease. Purified BMP 2, in conjunction with a suitable matrix, is sufficient to stimulate the synthesis of new bone (Wang et al., 1990). We have expressed recombinant human BMP-2 at high levels in Chinese hamster ovary cells using methotrexate-mediated gene amplification. Several forms of BMP-2 are secreted from CHO cells: (1) an amino-terminal propeptide of 40-45 kDa, (23) a mature active 30 kDa homodimer consisting of 18-22 kDa subunits, and (3) a small amount of uncleaved 60 kDa precursor protein. The mature, active protein is predominantly a 30 kDa homodimer consisting of subspecies of 18 and 22 kDa which differ by proteolytic processing at their amino termini. Mature BMP-2 and propeptide contain high mannose and complex N-linked oligosaccharides, respectively. The molar amount of secreted, processed propeptide is approximately 5-fold higher than mature BMP-2 in conditioned medium. BMP-2 associates with both the extracellular matrix and the surface of CHO cells, which may in part account for the unequal levels of extracellular propeptide and mature forms of the molecule in the conditioned medium. Recombinant BMP-2 can be expressed in sufficient quantities to assess its therapeutic potential for bone regeneration. PMID- 1419072 TI - Purification and biochemical characterisation of human and murine stem cell inhibitors (SCI). AB - We have recently characterised an inhibitor of haemopoietic stem cell proliferation (SCI/MIP-1 alpha) and report here on its purification and initial biological and biochemical characterisation. The activity can be detected by direct addition to the CFU-A stem cell assay and this simple test for inhibitory activity has greatly facilitated the purification of the molecule. The purification involves a combination of Mono Q ion exchange chromatography, heparin-sepharose affinity chromatography and Blue Sepharose affinity chromatography. The purified stem cell inhibitor is an 8 kD peptide which is identical to the previously described peptide macrophage inflammatory protein 1 alpha. The peptide has a natural tendency to form large self-aggregates and appears, in physiological buffers, to have a native molecular weight of around 90 kD. SCI is a heat stable, protease sensitive protein which is half maximally active at between 10 and 25 pM in the CFU-A assay. The self-aggregates can be disrupted by dilute solutions of acetic acid and it appears that disruption increases the specific activity of SCI preparations. We also report the characterisation of the human homologue of the stem cell inhibitor (human SCI/MIP 1 alpha) which is 74% identical to murine MIP-1 alpha and which shares all the above features of the murine inhibitor. PMID- 1419073 TI - Binding of a novel radioiodinated thromboxane A2/prostaglandin H2 antagonist to guinea pig lung membranes. AB - The utilization of a novel radioiodinated TXA2/PGH2 receptor antagonist, ISAP (7 [(1R,2S,3S,5R)-6,6-dimethyl-3(4- iodobenzenesulfonylamino)-bicyclo[3.1.1]-hept-2 yl]-5(Z)-heptenoic acid) to characterize TXA2/PGH2 receptors from guinea pig lung parenchymal membranes in radioligand binding assays is described. [125I]ISAP binding was saturable, displaceable, and dependent upon protein concentration. The time course of binding yielded k1 = 2.12 x 10(8) M-1 min-1, k1 = 4.46 x 10( 3) min-1, Kd = k-1/k1 = 17.8 pM. Equilibrium binding studies indicated a single class of high affinity binding sites with a Kd of 52.7 +/- 1.9 pM and a Bmax of 92.7 +/- 7.2 fmoles/mg protein (n = 4). Binding was inhibited by a series of structurally diverse mimetics and antagonists with the rank order of potency IBOP greater than ONO11113 = SQ26655 greater than U46619 (mimetics) and (d)-S-145 greater than ISAP greater than (1)-S-145 greater than SQ29548 greater than BM13505 = I-PTA-OH (antagonists), with entantioselectivity of binding demonstrated by (d) and (1) S-145. Binding was also inhibited by prostanoids (PGD2, PGF2 alpha, and 9 alpha, 11 beta-PGF2) thought to act at the airway TXA2/PHH2 receptor, but not by histamine or carbachol, and only weakly by LTB4 and LTD4, consistent with specific binding to the lung TXA2/PGH2 receptor. PMID- 1419075 TI - Structure elucidation of oxygenated lipids in human atherosclerotic lesions. AB - Oxidative modification of low density lipoproteins and tissue lipids has been proposed to be involved in the pathogenesis of atherosclerosis. We examined human atherosclerotic lesions of various stages from fifteen victims of acute heart failure and detected substantial amounts of oxygenated fatty acids in the tissue ester lipids. The degree of lipid oxygenation correlated with the stage of advancement of the lesion. More than 85% of the oxygenated fatty acids were localized in the cholesterol esters, whereas phospholipids contained only small amounts. Structure elucidation of the oxygenation products indicated a nonspecific product pattern of various isomers of keto- and hydroxy octadecadienoic acid. The data presented suggest an involvement of lipid peroxidation in the pathogenesis of atherosclerosis and indicate that the majority of the oxygenation products are formed via nonspecific, non-enzymatic reactions possibly initiated by the action of a 15-lipoxygenase. PMID- 1419074 TI - Aspirin abolishes the decreased low-density lipoprotein (LDL) entry into the rabbit arterial wall induced by the calcium channel blocker isradipine. AB - After deendothelialization and experimentally induced hypercholesterolemia in rabbits, an increased LDL entry into the vascular wall can be monitored using radiolabelled LDL. In male rabbits aged 6 months the abdominal aortic endothelium was removed by a Fogarty catheter. The animals fed a 1% cholesterol supplemented diet were treated either with isradipine (0.3 mg/kg/daily) (n = 36) alone or in combination with aspirin (5 mg/kg/daily) (n = 36) for four weeks. Thirty-six animals served as controls. 1, 3, 6, 12, 24 and 48 hours prior to sacrificing, 10 microCi 125I-LDL was administered intravenously to six rabbits in each group. The LDL entry was quantified in the abdominal aorta according to morphologically assessed type of surface lining. Aortic cholesterol content was assessed by Sudan III staining and quantitative determination. Endothelialized segments exhibited a significantly (p less than 0.05 - p less than 0.001) lower LDL uptake as compared to re- or deendothelialized segments. The LDL entry was significantly lower with isradipine treatment than in controls. In parallel the cholesterol content decreased and the Sudan-III-positive areas were smaller in size. This beneficial effect as well as that on aortic lipid content was abolished by a pretreatment with aspirin. While in the isradipine-treated animals PGI2 synthesis was significantly (p less than 0.01) enhanced, it was almost completely blocked by aspirin. These findings indicate that the benefit of reduced LDL entry caused by isradipine may be mediated by an increased endogenous PGI2 synthesis. PMID- 1419076 TI - Effect of prostaglandin E2 or prostaglandin synthesis inhibitors on human gonadotrophins and prolactin. AB - A role for prostaglandins (PGs) in the release of pituitary hormones in humans is controversial. The effect of PGE2 or PG synthesis inhibitors on gonadotrophin and prolactin (PRL) levels was evaluated in 50 volunteers (25 males and 25 females). Forty cases in four equal groups (Group I & II were males and group III & IV were females) received iv infusion of PGE2 in one cycle and non-steroidal anti inflammatory drugs (NSAID) [Indomethacin or Naproxen] in the subsequent cycle. Control groups A & B (5 males and 5 females) received saline infusions in one cycle and placebo capsules in the next cycle. Neither PGE2 nor any of the two NSAID altered the basal levels of FSH or LH significantly. PGE2 infusions in males depressed PRL levels significantly two hours after the onset of infusions. Indomethacin raised PRL levels while Naproxen did not. In women, a similar response was also observed but prolactin levels decreased earlier (30 min from the PGE2 infusion). These data indicate a probable role for PGE2 or other prostanoids as well in the regulation of human PRL release but not in gonadotrophin secretion. PMID- 1419077 TI - Effect of 25-hydroxycholesterol on cytotoxicity and prostacyclin production in cultured human umbilical arterial endothelial cells. AB - The effect of cholesterol or 25-hydroxycholesterol on DNA synthesis and prostacyclin synthesis by cultured human umbilical arterial endothelial cells was investigated. Cells incubated with 25-hydroxycholesterol showed an increased rate of cell death, decreased [3H]-thymidine incorporation and increased prostacyclin production as compared to either the control or the pure cholesterol group. 25 hydroxycholesterol caused a concentration- and time-dependent increase in prostacyclin synthesis. The intracellular free calcium concentration of endothelial cells incubated with 25-hydroxycholesterol was markedly increased in a time-dependent manner. Calcium uptake by endothelial cells incubated with 25 hydroxycholesterol for 24 h was markedly increased. It is suggested that 25 hydroxycholesterol may depress DNA synthesis and increase prostacyclin synthesis via an elevation in the intracellular free calcium concentration of endothelial cells. PMID- 1419078 TI - Thromboxane synthase inhibition in allergen challenged sheep lung: effect on eicosanoid synthesis. AB - We determined the effect of a novel inhibitor of thromboxane synthase, DP1904, on the baseline and allergen stimulated release of eicosanoids into the bronchoalveolar lavage fluid of sheep. DP1904 was effective in reducing the baseline and allergen stimulated production of TXB2. Inhibition of thromboxane synthase was associated with an increase in other prostaglandin endoperoxide metabolites, PGE2 and PGD2. Diversion of endoperoxide metabolism occurs in sheep lung tissue in vivo. PMID- 1419079 TI - Leukotriene formation by mouse connective tissue mast cells. AB - Stimulation of peritoneal cells from BALB/c, CBA/J or WBB6F1(-)+/+ mice with IgE/antigen caused the release of mast cell granules and leukotriene C4. No leukotriene formation was observed with peritoneal cells from mast cell-deficient WBB6F1-W/Wv mice. Mast cells (greater than 98% purity), separated on metrizamide gradients, did not synthesize detectable amounts of leukotriene C4 when challenged immediately after purification. Co-culture of the mast cells with 3T3 fibroblasts restored the capability of the mast cells to produce leukotrienes. Addition of IL-3 during culture enhanced the synthesis of this eicosanoid. The 5 lipoxygenase inhibitor A-63162 blocked the leukotriene formation. Western blot analysis confirmed the presence of 5-lipoxygenase in connective tissue mast cells. These experiments demonstrate that mouse peritoneal (connective tissue) mast cells can produce significant amounts of leukotrienes. PMID- 1419080 TI - A Calluna vulgaris extract 5-lipoxygenase inhibitor shows potent antiproliferative effects on human leukemia HL-60 cells. AB - A water-Calluna vulgaris extract (water-CVE) was found to be a relatively specific arachidonate 5-lipoxygenase inhibitor and showed potent anti proliferative effects on human leukemic HL60 cells. Water-CVE completely inhibited potato 5-lipoxygenase activity at 250 micrograms/ml, partially inhibited soybean 15-lipoxygenase at pH 7.4 and had no effect either on this 15 lipoxygenase at its optimal activity pH (pH 9) or on Lupinus albus 5-, 8-, 15 lipoxygenase. In culture, the proliferation and DNA synthesis of HL60 cells were decreased by water-CVE in a dose-dependent manner with an IC50 of 200 micrograms/ml at day 4. This effect of water-CVE is related to the starting density of HL60 cells. These results suggest that arachidonate 5-lipoxygenase metabolites and/or leukotrienes could play an essential role in cellular functions of leukemic cells and may explain the success of the use of Calluna vulgaris as tea and baths in folk medicine. PMID- 1419081 TI - Influence of HDL on the formation of 6-keto-PGF1 alpha and TXB2 in vitro: the importance of the source of HDL. AB - The influence of HDL, isolated from normolipidemic human blood and blood of normo and hyperlipidemic rabbits, on in vitro 6-keto-PGF1 alpha synthesis by rabbit aorta and on TXB2 synthesis by platelets of clotting human and rabbit blood was tested. The HDL fraction from normolipidemic subjects, when incubated with blood from normolipidemic humans or rabbits, inhibited TXB2 formation. The same fraction stimulated the formation of 6-keto-PGF1 alpha after incubation with rabbit aorta taken from normolipidemic animals. HDL taken from hyperlipidemic rabbits inhibited 6-keto-PGF1 alpha formation in rabbits and had no influence on TXB2 formation. These results support the hypothesis that not only is the absolute amount of HDL important for its influence on prostanoid formation, but also the origin and the composition of the HDL fraction. PMID- 1419082 TI - Membranes exert indirect negative control on phospholipase A2 (PLA2) in human placenta. PMID- 1419083 TI - Elevated maternal plasma immunoreactive phospholipase A2 in human preterm and term labour. AB - Peripheral plasma concentrations of immunoreactive phospholipase A2 (irPLA2) (Type II, non-pancreatic) were determined in 110 women during pregnancy. The concentration of irPLA2 did not significantly change during pregnancy (5.7 +/- 0.6 ng/ml, n = 72) until the onset of labour. When compared with non-labouring women, irPLA2 concentrations were significantly elevated in association with both preterm labour (13.3 +/- 2.4 ng/ml, n = 15, p less than 0.02) and labour at term (10.4 +/- 1.7, n = 23, p less than 0.02). These data suggest that maternal plasma irPLA2 may be reflective of the mechanism(s) underlying the labour-associated increase in human gestational tissue eicosanoid formation. PMID- 1419084 TI - [The inclusion of the family in the therapeutic process in dementia]. PMID- 1419085 TI - [Cognitive functions in multiple sclerosis]. AB - Although the presence of intellectual impairment in multiple sclerosis (MS) is known since the first studies of the disease frequently the impairment goes equally undetected for the patients, their family and the physician because the physical dysfunction is much more outstanding. In this study a population of 50 persons suffering clinically definite MS (Poser's criteria) and 50 healthy controls matched with the patients in sex, age and cultural level were submitted to a neuropsychological test battery (NPTB). The existence of a correlation between the punctuation obtained in the NPTB and factors such as the level of disability, the time of evolution, the type of MS and the work status was searched. The results show a greater difficulty in doing tasks requiring attention-concentration skills thus giving the MS patients significantly lower scores in the memory test when compared with the controls. The execution of all tests was worse in those forms of MS with the longest time of evolution, higher EDSS scores and the chronic-progressive types. In our study the loss of the working status was never due to the intellectual impairment, it was because of the physical disability. PMID- 1419086 TI - [Depression in Parkinson's disease and its relation to the cognitive and motor manifestations]. AB - Evaluation with the geriatric depression scale carried out in 30 patients with Parkinson's disease who did not present subjective complaint of loss of memory or impairment in superior mental function capable of interfering in daily routine showed a high frequency of depression of 50-70% depending on where the cut-off in the geriatric depression scale was located. Depression in these patients does not significantly relate with either cognitive impairment or the degree of motor incapacity. Neither were depression or anxiety in these patients related with demographic data such as the age of the patient, age at onset of the disease, sex, months of evolution, or education. In contrast, a positive correlation was found between depression and anxiety. PMID- 1419087 TI - [Ischemic cerebrovascular syndrome of pregnancy and the puerperium]. AB - There is little information on ischemic cerebrovascular pathology of pregnancy and puerperium. The clinical characteristics and the results of tomographic and angiographic evaluation of nine patients with ischemic cerebrovascular syndrome of pregnancy and puerperium are described. Venous thrombosis was the cause of cerebrovascular episode in 4 of the 9 patients presenting characteristic clinical manifestations and occurring particularly during puerperium. The diagnostic method of these cases was angiography since the scanner was normal in almost all the cases. Arterial pathology presented preferentially during pregnancy with no peculiar clinical characteristics being observed. In these cases the cerebral scanner was the best diagnostic technique. Follow-up suggested a better prognosis for venous pathology in terms of sequelae. PMID- 1419088 TI - [Cognitive functions in multiple sclerosis. Bibliographic review (1980-1991)]. AB - The presence of intellectual impairment in MS has been known since the first studies of Charcot and Vulpain who described the memory's weakening appearing in these patients. However, the interest for the MS' cognitive deficits has specially increased in the decade of the 80's. In this article, a bibliographical revision of the last published studies about the cognitive impairment in MS has been made paying attention to those superior functions known as more affected. The aim of this article is to known the correlation among the cognitive impairment and the MR images, level of disability, fatigue, duration and course of the disease and demographic factors. PMID- 1419089 TI - [Hemiparesis-ataxia in meningovascular syphilis]. AB - Two cases of lacunar infarction of "ataxic-hemiparesis" type secondary to luetic vasculitis are presented. The first patient presented meningovasculitis and the second progressive general paralysis. In both cases the ischemic lesion was seen by magnetic resonance and was located at a pontine level in one case and in the corona radiata in the other. Treponemal serology in plasma and CSF was positive in both cases with lymphocytic pleocytosis and high CSF protein levels being observed. Clinical and response to treatment was satisfactory except in the case of general paralysis in whom the impairments existing prior to the cerebral infarction persisted. This study complements recent communications in which neurosyphilis was attributed to the appearance of other lacunar type infarctions (pure motor hemiparesis). PMID- 1419090 TI - [Behcet's syndrome with neurological involvement: value of magnetic resonance]. AB - Behcet's syndrome is a rare inflammatory, multisystemic disease of unknown etiology and chronic relapsing course, manifested chiefly by ocular and mucocutaneous lesions. Among its neurologic complications, a cerebral vasculitis can occasionally been observed, upon which there is little information at present. A 31-year-old man presented with fever, weight loss, oral and genital ulcers, blurred vision and memory loss during the last two months. The cerebrospinal fluid contained 170 lymphocytes/microliters. Computed Tomography and cerebral angiography were normal. Magnetic resonance imaging (MRI) showed small hyperintense lesions in the corticomedullary and periventricular regions. The patient's condition improved with corticosteroids. We stress upon the importance of MRI to detect small-vessel vasculitis in Behcet's disease. PMID- 1419091 TI - [Current status of fine-needle myelography]. PMID- 1419092 TI - [Fibrodysplasia ossificans progressiva: evaluation of the signs in an imaging study]. PMID- 1419093 TI - [Amyotrophic lateral sclerosis and physical exertion]. PMID- 1419095 TI - The 1991 Elis Berven Lecture. Radiotherapy in the nineties. Increase in cure, decrease in morbidity. AB - Advance in radiotherapy can be achieved by obtaining a greater tumour control and by reducing the morbidity of treatment, both early and late. The factors influencing both means of benefiting the cancer patient are considered. PMID- 1419094 TI - [Adenosine deaminase. False negatives in tuberculous meningitis]. PMID- 1419097 TI - Clinical aspects of tumour involvement of the pulmonary vessels. AB - The involvement of the pulmonary vessels by tumour emboli may lead to a clinical picture defined as 'subacute cor pulmonale'. Information about this syndrome has been limited to case reports and a few series. A study of 214 autopsied cancer patients was undertaken to investigate the clinical signs and symptoms of tumour involvement of the pulmonary vessels (TIPV). The lungs were removed as a block and 15 sections (3 from each lobe) were analyzed. Clinical data about right ventricular failure, dyspnoea, cough, pleuritic chest pain, cyanosis, engorgement of jugular veins, peripheral oedema, haemoptysis and haemoptoic sputum were obtained from the medical records of each patient. Tumour emboli were detected in 89 cases, and no respiratory symptoms were recorded in 39. The presence of dyspnoea and cyanosis were highly significant in the group with TIVP, and right ventricular failure and peripheral oedema showed slight significant differences between the patients with and without TIPV. The classical picture of subacute cor pulmonale was observed in 13 patients and TIPV was considered to be the main cause of death in 29 cases. Our results indicate that although the development of subacute cor pulmonale was rare in patients with cancer, TIPV may be suspected when the patient presents respiratory distress and should be included in the differential diagnosis of dyspnoea in cancer patients. PMID- 1419096 TI - Diagnosis and treatment of anal carcinoma. An overview. AB - Squamous cell carcinoma of the anal canal gives early symptoms and is easy to diagnose. However, these patients often present with advanced tumours, probably because of patient's and/or doctor's delay. The diagnosis must be confirmed by a conclusive biopsy as the treatment of ano-rectal tumours is based upon correct histopathological diagnosis. Loco-regional tumour control of squamous cell carcinoma is excellent following radiotherapy or combined chemoradiotherapy as only 10-20% of the patients develop a local recurrence. The great majority of these are cured by abdominoperineal resection. However, this treatment involves considerable acute and chronic toxicity, but mortality is less than 2%. There is no general agreement about how to minimize toxicity without hazarding loco regional tumour control. One way could be to irradiate only the primary tumour site in patients with early lesions, and reserve radiotherapy of regional lymph nodes for more advanced cases. About 20% of the patients develop distant metastases, which make the disease incurable. Hence, frequent, rectal digital examination is the most important follow-up since early local recurrences can easily be cured. There is no general consensus concerning adjuvant chemotherapy, but its potential should be further explored. PMID- 1419098 TI - Primary gastric non-Hodgkin's lymphoma. A retrospective clinico-pathological study. AB - Prognostic factors and treatment results were analysed in 72 consecutive patients with primary gastric lymphoma treated between 1970 and 1985. There were 37 patients in stage IE, 17 in IIE, 3 in IIES and 15 in stage IV. Histopathological re-evaluation and classification according to the TNM system were performed. We found that disseminated disease (stage IV), serosal penetration (T3), involvement of adjacent organs (T4) and extensive abdominal lymph node involvement (N3) were poor prognostic factors. Neither histological malignancy grading, nor the appearance of lympho-epithelial lesions were significantly associated with relapse-free survival. Forty-six patients with 'limited localized' disease (stage IE, IIE, N3 excluded) received potentially curative treatment (surgery, radiotherapy, chemotherapy or combinations thereof), of whom 85% remained relapse free. Thirty-four patients did only get local treatment (surgery and/or radiotherapy) with curative potential, the relapse-free survival rate was 85%. We conclude that primary gastric lymphoma stage IE and IIE (N3 excluded) is often a truly localized disease that can be cured with local therapy. PMID- 1419099 TI - Age as a determinant of axillary node involvement in invasive breast cancer. AB - We analyzed the age at diagnosis and the tumor size as determinants of axillary node involvement in 725 consecutive patients with breast cancer. The prevalence of nodal involvement increased consistently with tumor diameter from 18.9% in tumors smaller than 10 mm to 72.9% in those measuring 40 mm, or more. The risk also varied with age, the lowest prevalence being found in the youngest and the oldest patients and the highest one in the 40-59-year age group. When analyzed as a continuous variable age was best fitted as a second order term and it was a statistically significant (p = 0.04) determinant of axillary metastases in a multivariate model where tumor diameter, histopathological classification and estrogen receptor concentration were taken into account as possible confounding variables. The findings indicate that the parallelism between the establishment of metastases in lymph nodes and at distant sites may vary with age. The prognostic value of nodal status may therefore depend on age at diagnosis. PMID- 1419100 TI - Measurement of short-term 11C-thymidine activity in human head and neck tumours using positron emission tomography (PET). AB - Tumour uptake of 11C-thymidine labeled in the methyl position was assessed after intravenous injection in 13 patients with head and neck tumours. This activity was compared to other tracers such as C15O, 13NH3 and C15O2. In every single case a 'positive' tumour image after injection of 11C-thymidine was obtained. Time activity curves showed the initial activity to be followed by a rapid decrease over the first 10-15 min with an apparent plateau thereafter. A similar level of uptake was found in normal salivary gland regions and myocardium, while higher activities were noted in liver and kidney parenchyma. It is suggested that both blood flow and cellular metabolism can influence 11C-thymidine imaging in this class of human tumours. PMID- 1419101 TI - Primary malignant lymphoma of the brain. A report of 24 cases from the Norwegian Radium Hospital. AB - Between 1975 and 1987, 24 patients with primary central nervous system lymphoma were seen and treated at the Norwegian Radium Hospital. The overall median survival was 24 months. Patients with poor performance status (WHO 3-4) had a median survival of 3 months whereas patients with good performance status (WHO 0 2) had a median survival of 40 months (p < 0.0001). Patients who were not steroid dependent after operation had a better survival than those patients who were steroid-dependent (p = 0.02). Nine patients were still living without evidence of disease at last follow-up, 18-130 months after the initial treatment. PMID- 1419102 TI - Primary non-AIDS related brain lymphoma. Patterns of failure following radiotherapy. AB - Thirteen patients with primary brain lymphoma (PBL) were treated with radiotherapy. Three patients also had ocular involvement with retinal masses at initial presentation. All but one patient received conventional whole brain irradiation and, in addition, spinal irradiation, intrathecal methotrexate or orbital irradiation were given in two, two and four patients respectively. The radiation doses for involved sites ranged from 40 to 65 Gy, and for prophylactic sites from 30 to 50 Gy. After radiotherapy, all patients had complete regression of the tumor on computed tomography. Nine patients relapsed, 5 of them with brain recurrence. Two patients had ocular recurrence exclusively as their first relapse. The remaining two relapsing patients had bone lesions. One patient died intercurrently. As a result, only three patients are alive and free of disease after 16 to 36 months and all three received some adjuvant treatment in addition to whole brain irradiation. PMID- 1419103 TI - Prognostic factors in radiation-treated esophageal carcinoma. AB - Prognostic factors in esophageal carcinoma treated with irradiation were examined. The prognosis of 111 patients without metastasis who had received more than 60 Gy was analyzed. Significant associations were found between survival rates and tumor length, stage, radioresponse of the primary tumor and the s.c. X P classification based on barium contrast radiography; superficial type (tumor limited to the surface of the esophageal wall), tumorous type (solid mass without ulceration), Ul-A type (tumor with shallow ulceration with regular margin), Ul-B type (tumor with deep ulceration or irregular ulcer margin), and funneled type (tumor invading the esophageal wall in a scirrhous pattern). In multiple regression analysis, the X-P classification had the strongest correlation with survival and the survival rates of patients with the superficial type, the tumorous type and the s.c. Ul-A type were significantly higher than those of patients with the other tumor types (p < 0.001). PMID- 1419104 TI - The effect of postoperative radiotherapy on leukocyte zinc, serum trace elements and nutritional status of breast cancer patients. AB - Mononuclear (MNC) and polymorphonuclear cell (PMNC) zinc content was determined together with serum zinc, copper, selenium and iron concentrations in 24 operable breast cancer patients during and after postoperative radiotherapy. Anthropometric and biochemical indices of nutritional status were measured as background data. The measurements were carried out in the years 1987-1988. Nine patients used unconventional multivitamin or trace element preparations. A steady but statistically insignificant decrease in PMNC zinc was seen during treatment. No changes occurred in MNC zinc. Serum copper levels increased in five patients possibly due to tamoxifen treatment, but no other alterations occurred in serum trace element levels. Appetite was well maintained and nutritional status remained unaltered. Postoperative radiotherapy for breast carcinoma had thus no effect on either trace element or nutritional status. Patient-initiated alternative treatments did not significantly affect their trace element levels. This was probably due to small supplementation doses or irregular use of the preparations. PMID- 1419105 TI - Ondansetron and tropisetron with dexamethasone in the prophylaxis of acute vomiting induced by non-cisplatin-containing chemotherapy. AB - Forty-seven patients receiving non-cisplatin-containing chemotherapy were entered in a prospective study in which the efficacy of ondansetron plus dexamethasone and tropisetron plus dexamethasone in the prophylaxis of acute vomiting was evaluated. Thirty-nine patients were evaluable for cross-over analysis. During the 24 hours following the start of chemotherapy, 97% of patients on ondansetron plus dexamethasone reported total control of vomiting compared with 82% of those on tropisetron plus dexamethasone (p = 0.026). Thus, both 5-HT3- receptor antagonists combined with dexamethasone were highly effective in controlling acute vomiting induced by non-cisplatin-containing chemotherapy. The observed difference between the treatments may be caused by different dose schedules of ondansetron and tropisetron. A double-blind design with equal number of placebo controlled administrations is needed to ascertain whether there is a significant pharmacological difference between ondansetron and tropisetron. PMID- 1419106 TI - Modification of radioresponse of sublethally irradiated mouse jejunum by misonidazole. AB - The radiation-induced changes in a critically radiosensitive tissue, jejunum of BALB/c mice and their modification by a hypoxic cell sensitizer, misonidazole (MISO), were studied. Adult mice were exposed to 1.5, 3.0 and 5.0 Gy of 60Co gamma radiation 30 min after MISO injection and quantitative studies in jejunal cross sections were carried out at different post-treatment times from 3 h to 28 d. Radiation-induced damage to the jejunal mucosa was dose-dependent and reached a maximum on day 1 post-treatment in all the groups. MISO pretreated animals did not exhibit any change in the crypt survival or crypt and villous cellularity compared to the radiation alone group. However, there was a significant suppression of mitotic activity by MISO at early intervals after irradiation. This reduction in mitosis in the drug pretreated animals appeared to affect the rate of recovery from radiation damage, which was slower and prolonged compared with that in the radiation alone group. PMID- 1419108 TI - Carcinoma of unknown primary site--a complete and sustained response with interleukin-2, alpha interferon and 5-fluorouracil/leucovorin. PMID- 1419107 TI - Neutropenic enterocolitis and intestinal perforation associated with carboplatin containing conditioning regimen for autologous bone marrow transplantation. PMID- 1419109 TI - Acute cerebrovascular accident after treatment with cisplatin. PMID- 1419110 TI - Binding of cytotoxin P4 from Naja nigricollis nigricollis to B16F10 melanoma and WEHI-3B leukemia cells. AB - Cobra venoms cause irreversible destruction of cells cultured in vitro [1,2]. The venom of Naja nigricollis nigricollis possessed the most potent cytotoxic activity towards B16F10 melanoma cells among various examined venoms [2]. The main cytotoxic factor (P4) isolated from this venom showed preferential activity on tumor cell lines and caused lysis at concentrations of 10(-7) M (0.8-1 micrograms/ml) [3]. The present study examined the binding of cytotoxin P4 to melanoma B16F10 and WEHI-3B leukemia cell lines and found that, like cytotoxicity, it depended on concentration, temperature and incubation time. Cytotoxin concentrations that elicited no apparent damage to cells during the first hour of incubation caused lysis after a longer period of incubation, suggesting that a critical number of bound molecules is required in order to cause cell death. Bivalent ions, such as Mg2+, Ca2+ or Sr2+, which decreased binding to the cells also inhibited cytotoxicity. Competition experiments as well as the displacement of 75% of the bound radiolabelled cytotoxin with 'cold' cytotoxin, suggest the presence of specific binding sites for the toxin in the examined tumor cells. The non-specific binding of the cytotoxin P4 to sea urchin ova and sperm cells without affecting their fertility, even at high concentrations of 10(-5) M, indicates that the specific binding to cells is probably a necessary condition for cell lysis. PMID- 1419111 TI - The effect of the presence of integral membrane protein (human band 3) on the membrane lytic properties of melittin in reconstituted systems. AB - Reconstitution of the anion exchange protein from human erythrocytes (band 3) into phospholipid vesicles was shown to have a protective effect on melittin lysis of the vesicles when compared to pure lipid vesicles. Low salt buffer was found to cause an inhibition of lysis in both proteoliposomes and pure lipid vesicles compared to salt buffer. High phosphate concentration did not seem to cause inhibition of lysis in the reconstituted system. However, an inhibition is observed in pure lipid vesicle control, which is contradictory to previous reports. PMID- 1419112 TI - The synthesis and function of the Escherichia coli hemolysin and related RTX exotoxins. AB - The RTX group of exotoxins represents a branch of a family of exoproteins produced by Gram-negative bacteria which share the properties of being secreted by a leader-independent pathway and a tandemly-repeated nine-amino-acid sequence that is responsible for calcium binding. The Escherichia coli hemolysin (HlyA) is the prototype for the RTX exotoxin family which includes the leukotoxins of Pasteurella haemolytica and Actinobacillus actinomycetemcomitans and hemolysins from four Gram-negative genera. A review of the genetics, synthesis, export and target cell reactivity of the E. coli hemolysin is given. An evolutionary tree of the RTX toxin family based on amino acid sequence similarity is presented. PMID- 1419113 TI - Activation of Escherichia coli prohemolysin to the membrane-targetted toxin by HlyC-directed ACP-dependent fatty acylation. AB - Hemolysin (HlyA) and related toxins of Escherichia coli and other Gram-negative pathogenic bacteria form membrane pores in cells of the host immune system, causing cell dysfunction and death. An insight into the mechanism by which HlyA is targetted to mammalian cell membranes was achieved by establishing in vitro activation of the non-toxic precursor proHlyA. By this approach we have discovered that conversion of proHlyA to the post-translational active HlyA toxin is determined by fatty acylation of proHlyA in an apparently novel process directed by the HlyC homodimer activator protein, and dependent upon the cellular acyl carrier protein (ACP). By further exploiting the in vitro activation system it is now possible to obtain direct evidence that HlyC binds to an internal recognition sequence in the proHlyA precursor, in this way providing specificity for the transfer to proHlyA of a fatty acid moiety carried by the ACP. It is possible that the fatty acid modification determines directly the binding of HlyA to mammalian membrane lipids, thus initiating the toxin interaction with the target cells. PMID- 1419114 TI - The HlyB/HlyD-dependent secretion of toxins by gram-negative bacteria. AB - Hemolysin (HlyA) and related toxins are secreted across both the cytoplasmic and outer membranes of Escherichia coli and other pathogenic Gram-negative bacteria in a remarkable process which proceeds without a periplasmic intermediate. It is directed by an uncleaved C-terminal targetting signal and the HlyD and HlyB translocator proteins, the latter of which are members of a transporter superfamily central to import and export of a wide range of substrates by prokaryotic and eukaryotic cells. Our mutational analyses of the HlyA targetting signal and definition for the first time of stages and intermediates in the HlyB/HlyD-dependent translocation allow a discussion of the hemolysin export process in the wider context of protein translocation. PMID- 1419115 TI - Oligomer formation of staphylococcal alpha-toxin analyzed by electron microscopy and image processing. AB - The 12S oligomeric form of Staphylococcus aureus alpha-toxin has been studied with electron microscopy after incubation of the toxin with membrane preparations or liposomes. The target material originated from human platelets. Different electron microscopic preparation techniques were used including negative staining, freeze-fracture and vitrification in liquid ethane. Analysis of micrographs with image processing methods revealed two groups of ring-like structures corresponding to alpha-toxin oligomers. One form measured 75 A in diameter and had a high stain density in the central protein deficient part while the other was larger with a diameter of 100 A and less stain accumulation in the center. The conditions under which the latter were formed suggest that this corresponds to an inactive loosely-bound form of the toxin. The high stain density in the smaller particle is consistent with the presence of a penetrating pore in this structure. PMID- 1419116 TI - Specific and non-specific mouse protection induced by different chemotypes of the Pseudomonas aeruginosa lipopolysaccharides. AB - Lipopolysaccharides (LPS) of Pseudomonas aeruginosa were studied by the mouse active, cross-protection test. The primary structure of O-specific polysaccharides (O-repeating units) of different chemotypes was determined and their cross-protective activity demonstrated. Low doses of LPS (0.1-1 micrograms) stimulated chemotype-specific protection against P. aeruginosa in mice. This immunity was associated with the primary structure of the LPS and it lasted for 14 days after the first or second immunization. High doses of LPS (10-100 micrograms) induced cross-protection against P. aeruginosa in mice. The cross protective capacity was caused evidently by the secondary structure or conformation of LPS molecule, i.e. by the common conformational protective determinant. This cross-protection lasted for only 5 days after the first or second immunization. PMID- 1419117 TI - Mechanism of the protective immunity against murine typhoid: persistence of Salmonella L forms in the liver after immunization with live-cell vaccines. AB - Live-cell vaccines of Salmonella typhimurium, either a sub-lethal dose of a wild type (strain LT2) or a high dose of its two-heptose Rd1 mutant (strain SL1004), induced acquired resistance to murine typhoid, which remained 180 days after immunization. Growth of S. typhimurium as a bacillary form ceased between days 30 and 60 of immunization, but L forms of this bacterium colonized the liver (the mean number of L forms in the liver: 600 L-forming units) even at 180 days post immunization. In contrast, a high inoculum of either a Ra mutant (strain TV148) of strain LT2 or S. schottmulleri 8006 sharing the same O antigenic components with those of S. typhimurium induced only a short-lived protection in proportion to the number of L forms in the liver, and the protective immunity was lost before day 180. However, there was no significant difference in the salmonella specific T-cell responses among groups of immunized mice on day 180 of immunization. A lethal infection with strain LT2 in mice which had been immunized 75 days previously with living cells of strain SL1004 resulted in a rapid clearance of the challenge inoculum, together with a rapid elevation of anti-S. typhimurium antibody responses. Thus, the present data suggest that the long lived immunity conferred upon live S. typhimurium vaccines is attributable to the colonization of this bacterium in the liver as L forms and the ability to colonize the liver as L forms is independent of the chain length of salmonella O antigens. PMID- 1419118 TI - Immunogenicity and toxicity of lipopolysaccharide from Francisella tularensis LVS. AB - Lipopolysaccharide (LPS) from the live vaccine strain of Francisella tularensis (F. tularensis LVS) was isolated and purified. The LPS did not stimulate lymphocytes from previously tularaemia-vaccinated individuals or lymphocytes from non-primed individuals. However, serum antibodies from tularaemia vaccinees reacted with the LPS whereas virtually no reactivity was found with antibodies from individuals not exposed to F. tularensis LVS. Antibodies of immunoglobulin class M displayed the antibody reactivity predominantly. The LPS failed to induce the mononuclear cell-derived cytokine interleukin-1 and only low levels of tumour necrosis factor were detected. Furthermore, no LPS endotoxin properties were found in galactosamine-treated mice or in the Limulus amoebocyte lysate assay. From these results it can be concluded that F. tularensis LVS possesses a lipopolysaccharide-like molecule, which does not exhibit properties of a classical endotoxin. PMID- 1419119 TI - Phagocytosis of polymorphonuclear leukocytes by guinea pig peritoneal macrophages: effects of serum and temperature in vitro. AB - The regulation of phagocytosis of neutrophils by peritoneal macrophages was studied in vitro. Peritoneal exudate cells (PECs) of guinea pigs were lavaged 15 h after the i.p. injection of thioglycollate medium and were cultured in chamber slides. When PECs were cultured in RPMI 1640 medium in the absence of serum, approximately 20% of the macrophages phagocytized autologous neutrophils during 48-72 h of culture. Addition of guinea pig serum to the culture (2.5-20% v/v) suppressed the extent of the phagocytosis. The suppression was induced by globulin-rich ammonium sulfate fractions of the serum. Sera from rat, mouse, hamster, horse or calf also suppressed the phagocytosis, but fetal bovine serum (FBS) supported the phagocytosis, which was inhibited by globulin-rich Cohn fractions of bovine serum. The rate of neutrophil-phagocytosing macrophages was proportional to the rate of the pyknotic change of neutrophils. At a high temperature (42 degrees C), the autophagocytosis took place at 12 h of culture when fresh, but not heat-inactivated, autologous serum was added, implying that complement components may play a role in the hyperthermia-induced phagocytosis of neutrophils by macrophages. At 42 degrees C, ingested neutrophils did not show the pyknotic changes, indicating that intact neutrophils were ingested by macrophages. PMID- 1419120 TI - Clinical experience with Tc-99m labeled (N2S2) anti-melanoma antibody fragments and single photon emission computed tomography. AB - We evaluated the imaging capability of murine Tc-99m-labeled antimelanoma Fab fragments in 12 patients with clinical stage II and III melanoma. Tc-99m-NRX118.7 antimelanoma Fab fragment, 10.0 to 27.2 mCi (370-1, 006 MBq), was injected IV 30 min after irrelevant nonspecific intact antibody and 5 min after intact specific antibody were given. In all patients, whole-body scans and spot views were obtained. Single photon emission computed tomography (SPECT) was additionally performed in eight of the patients. The procedure was well tolerated, and 31 of 38 known foci of melanoma were detected (sensitivity, 82%). SPECT aided in detecting and better localizing lesions in the head, neck, and chest. The specificity of the technique was satisfactory when interpretation was performed with a knowledge of normal sites of accretion and excretion of technetium-99m activity such as the kidneys and gut. In several instances, lesions were discovered by means of the antibody scan before detection by other methods, and in two instances, the lack of visualization on antibody scan of a palpable mass correctly indicated that no melanoma was present in the mass. Scan results in three patients led to alterations in patient care; including preventing aggressive surgical and nonsurgical treatments. Although these data are encouraging, evaluation in additional patients will be essential to determine the clinical utility of this antibody scan in the management of patients with melanoma. PMID- 1419121 TI - Using quantitative coronary arteriography to redefine SPECT sensitivity and specificity. AB - Previous studies looking at the sensitivity, specificity, and predictive accuracy of single photon emission computed tomography (SPECT) have been based upon the results obtained by visual interpretation of coronary arteriograms. Since the results of visual and quantitative determination of percent diameter stenosis have been shown to be statistically different, the results obtained from SPECT imaging when compared to quantitative methods for assessing coronary artery disease would be expected to provide a more correct assessment of sensitivity, specificity, and predictive accuracy. To determine the "true" sensitivity, specificity, and predictive accuracy of SPECT in diagnosing coronary artery disease, this study compared the results obtained in 44 SPECT images (20 thallium and 24 teboroxime) with the results obtained when quantitative coronary arteriography was used to analyze the coronary arteriograms. These 44 cases were then compared against 8 different definitions of significant coronary artery disease, varying from 30 to 80%, to yield 352 comparisons. The maximum specificity and predictive accuracy was found when 45% diameter stenosis was used to define the presence or absence of significant disease. At 45% diameter stenosis, SPECT imaging demonstrated an 86% sensitivity, 78% specificity, and 94% predictive accuracy with only 6% false positives. In 100% of the cases where 45% diameter stenosis was used to define the presence of disease and exercise failed to demonstrate ST segment changes or angina, when SPECT imaging demonstrated a perfusion defect(s), quantitative coronary arteriography agreed with SPECT imaging results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419122 TI - Multiple organ platelet sequestration, hemodynamics, and gas exchange in endotoxin shock and the effects of aspirin-terbutaline treatment. AB - We studied the effects of two different drugs on multiple organ platelet sequestration, hemodynamics, and respiratory function during endotoxin shock. Twenty-eight sheep (four groups) were anesthetized and ventilated. Group AT-E received aspirin and terbutaline 30 min before and group E-AT 30 min after Escherichia coli endotoxin. Group E also received endotoxin but no drug treatment (shock controls), and group C received neither endotoxin nor drug treatment. There was a marked platelet trapping in the lungs and in the liver immediately after administration of endotoxin in groups E and E-AT, but after 4 hr it was less pronounced in group E-AT than in the endotoxin controls (P < 0.05). In the pretreated animals (group AT-E) there was no increase in platelet sequestration until almost 2 hr after endotoxin both in the lungs and the liver, but at the end of the study (240 min) there was no difference between the pre- and posttreated groups. No significant changes occurred in the kidneys and spleen in any of the groups. In groups E and E-AT the endotoxin infusion resulted in 200% rise in pulmonary artery pressure (PAP) and a sharp decrease in mean arterial pressure (MAP; 25-30%), respiratory compliance (CT; 50%), arterial oxygen tension (PaO2; 70%) as well as in oxygen delivery index (DO2; 30-40%) within 30 min. After 4 hr the PAP had decreased significantly in group E-AT, but remained high in group E (> 100% higher than in group C). Also MAP, PaO2, DO2 and CT improved slightly in group E-AT, while they remained low in group E.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419123 TI - Sonographic evaluation of physiologic bolus volume in oral swallowing. AB - Twenty-two nondysphagic normal subjects were sonographically studied to define the average volume of a physiologic fluid bolus. Several varying volumes (5, 10, 15, and 20 ml) of water were given to assess the average size of the swallowed bolus. At the onset of oral deglutition, when placed between the dorsum of the tongue and the groove of the hard palate, the bolus has an ellipsoidal shape, thus permitting sagittal, axial, and coronal measurements. Our results indicate that swallowed bolus volume rises proportionally to water bolus given up to 15 ml and that the average size of a physiologic fluid bolus is 7 ml. PMID- 1419124 TI - Pathophysiologic considerations in carotid artery imaging: current status and physiologic background. AB - Carotid endarterectomy now has an established place in the management of selected patients with carotid artery disease. This success rests in part on the invasive and non-invasive techniques available for imaging of both the pre- and postsurgical carotid artery. While contrast angiography has retained its place as a key presurgical imaging procedure, newer methods, including Doppler ultrasound, MRI angiography, SPECT, and PET scanning are providing additional anatomic, physiologic, functional, and biochemical information. An understanding of the complementary roles of these procedures is helpful to providers working to prevent strokes of carotid origin. PMID- 1419125 TI - Impact of very low birthweight on the black-white infant mortality gap. AB - In recent years, the rate of decline for the black infant mortality risk (IMR) has been slower than that for whites. The resultant widening in the black-white infant mortality gap has been accompanied by an increased percentage of very low birthweight (VLBW) infants (227 g-1,499 g) among black live births. Restricting our analysis to non-Hispanic black and white single live births, we used the 1983 national linked birth-death file to assess the relative contribution of VLBW infants to the black-white gap in IMR. VLBW occurred among 2.3% of all black live births and among 0.8% of all white live births. Deaths among VLBW infants accounted for 62.5% of the black-white gap in IMR. Although VLBW newborns represent a fraction of all live births in the United States, they account for almost two-thirds of the black-white gap in IMR. Since preterm delivery is associated with most VLBW infant deaths, our findings indicate the crucial need to identify strategies that reduce preterm births, among blacks in particular, to reduce significantly the infant mortality gap in the United States. PMID- 1419126 TI - Relationship of maternal smoking during pregnancy to placenta previa. AB - Although maternal smoking during pregnancy is reportedly associated with placenta previa, its etiology is unknown. We examined this association by using North Carolina vital records of 1988 and 1989. Among women who smoked 0, 1-9, 10-19, and > or = 20 cigarettes per day during pregnancy, the prevalence of placenta previa at delivery was 3.8, 5.7, 6.3, and 6.7 per 1,000 singleton live births, respectively, in the entire population. However, after the potential confounders (maternal age, race, gravidity, parity, previous pregnancy terminations, previous cesarean section, and gestational age) were controlled by individual matching, the adjusted overall odds ratio (OR) was 1.29 (95% confidence interval [CI] 1.05, 1.58) with slight dose-response gradients. Our study indicates that, although maternal smoking during pregnancy might affect placenta previa, the magnitude is substantially smaller than previously reported. This association may be attributable to other factors, such as detection bias. PMID- 1419127 TI - Prevention of tuberculosis in children: missed opportunities. AB - We conducted an eight-year prospective investigation in Tennessee of all cases of tuberculosis (TB) reported statewide in children younger than 15 years of age. Of the 109 verified childhood cases reported from 1981 to 1988, at least 23 (21%) were preventable. Eleven children developed the disease while they were under surveillance but were not receiving preventive therapy, nine cases resulted from failure of health care providers to conduct timely contact interviews/investigations, and three were due to other reasons. Improved surveillance, increased use of preventive therapy, and ensured compliance will contribute significantly to the elimination of tuberculosis in children at high risk of developing the disease. PMID- 1419128 TI - Agreement between patient self-reports and medical records for Pap smear histories. AB - As part of a larger cervical cancer study, we tried to verify the Pap smear histories for 125 black women with cervical cancer. For 105 of the patients, we identified all possible providers for the five-year period before the calendar year of diagnosis. Agreement between the medical records and the patient reports was poor to fair (kappa = 0.34) for whether the patient had a Pap smear in the three-year period before diagnosis. Patients tended to report far more Pap smears than medical records confirmed. Important determinants of agreement were the number of Pap smears reported during the five-year period and the age of the patient. The older the patient and the more Pap smears reported, the larger the discrepancy between the medical record and her self-report. The medical records did not contain enough data for us to complete an investigation of the possible reasons for this disagreement. Our results suggest these implications: (1) clinicians should strongly consider performing Pap smears if they doubt a patient's screening history, and (2) Pap smear registries are required for reliable and efficient evaluations of cervical cancer control programs because neither the patient report nor medical records are adequate. PMID- 1419130 TI - Prevalence of Chlamydia trachomatis infection among women in a multiphysician primary care practice. AB - I screened 312 women, 18-45 years of age, presenting for routine gynecologic examination or prenatal care in a multiphysician primary care practice for Chlamydia trachomatis and Neisseria gonorrhoeae. I evaluated age, pregnancy, payment status, and presence of clinical cervicitis or gonorrhea as possible predictors of risk for chlamydial infection. Compared to culture, the direct immunofluorescent antibody (DFA) test used to screen for C trachomatis had a sensitivity of 70% and a specificity of 97%. By culture, the overall prevalence of chlamydial infection was 3.2% (confidence limits [CL] = 1.1-5.9) with a prevalence of 2.2% in nonpregnant women and 9.3% in pregnant women. Overall prevalence by the DFA test was 5.45%. Pregnancy status and youth were the significant predictors of risk for infection as determined by culture but not by Microtrak. Payment status, clinical cervicitis, and gonorrhea cultures were not useful predictors of increased risk. I discuss the implications of using culture, an imperfect "gold standard," for determining sensitivity, specificity, and prevalence. PMID- 1419129 TI - The use of cervical cytology to identify women at risk for chlamydial infection. AB - Testing asymptomatic women for chlamydial infection is advocated for high-risk populations, but testing criteria in low-risk settings are less clear. To determine whether findings from Papanicolaou (Pap) smears could identify women at risk for Chlamydia, we studied 512 women, 18 to 50 years of age, seeking routine gynecologic care. The prevalence of positive cultures for Chlamydia was 4.7%. Three cytologic findings were independently associated with Chlamydia on logistic regression: transformed lymphocytes, polymorphonuclear leukocytes, and squamous metaplasia. The sensitivity and the specificity of the presence of any two of these three findings were 75% and 73.6%, respectively. The prevalence of Chlamydia if two findings were present was 12.2%, nearly three times the population prevalence. Certain findings on cervical cytology may be useful as an adjunct in preventive care for chlamydial cervicitis. PMID- 1419131 TI - Trend analysis of social and economic indicators of mammography use in Hawaii. AB - We examine the relationship between ethnicity and income as determinants of mammography use over a span of four years as a means of assessing community intervention impacts. The sample consisted of 1,447 women older than 34 years, living in Hawaii, who participated in the Behavioral Risk Factor Surveillance System (BRFSS). The percentage of women in the sample reporting a screening mammogram within the past two years was 31.4% in 1987, 54.1% in 1989, and 51.6% in 1990. Women of Hawaiian ancestry had the lowest percentage of mammogram use in the past two years (38.7%), while Japanese women had the highest percentage (49.8%). Results of logistic regression analysis indicate a significant increase in mammography use from 1987 to 1989 and no difference from 1989 to 1990. Findings also showed an association between age, income, and ethnicity with use in the past two years. Greater age, higher income, and Japanese origin, compared to Hawaiian, were all independently associated with increased odds of having had a mammogram in the past two years. We discuss results in terms of program evaluation and future research implications for community health surveys. PMID- 1419132 TI - Female employee participation in a worksite mammography screening program. AB - We conducted a survey of 1,184 women 35 years of age or older who were employees of a company in Los Angeles County, California, to determine why some women participated in a worksite mammography screening program whereas others did not. Of the 111 who accepted a mammogram, 90 responded to the survey; of the 1,073 who declined mammography, 620 responded. The women were predominantly white, were well educated, and had health insurance. Of the 111 women who received mammograms, one was diagnosed with carcinoma. Seventy-three percent of the respondents to the survey 40 years of age or older who declined mammograms had already fulfilled American Cancer Society (ACS) guidelines for mammography screening at the time of the program. Women who accepted a mammogram were more likely to have had at least one previous mammogram than were women who had not met ACS guidelines yet who declined screening. We conclude that many female employees who are white, are well educated, and have health insurance may not participate in a worksite mammography screening program because they have been screened elsewhere. Companies providing worksite mammography screening should target education to women who have not met ACS guidelines, especially those who have never had a mammogram. PMID- 1419133 TI - Sensitivity and specificity of lump detection in breast models. AB - Lump detection accuracy in models provides an index of ability to detect lumps in breast tissue. Recent research suggests poor lump detection accuracy in nontrained persons. Following individualized nurse-provided instruction in breast self-examination (BSE), 113 well-educated white women exhibited 89% mean lump detection sensitivity and 81% mean specificity (sensitivity = number of lumps correctly identified divided by actual lumps; specificity = percentage of exams completed without detection of false lumps). Problems with hands were potentially linked to poor specificity. Completeness of search was significantly associated with sensitivity. Lumps most unlikely to be detected were those in the fleshy upper outer quadrant of torso models. High accuracy levels here may be attributable to timing of assessments, homogeneous sample, models used, numbers/sizes of lumps, and long search times. BSE instruction should emphasize complete search, examination of outer quadrant of breasts, and assessment of hand problems. PMID- 1419134 TI - Narrowing the gap in health status of minority populations: a community-academic medical center partnership. AB - A major challenge in the United States is to narrow the gap in the excess morbidity and mortality rates of minority populations. This article presents a synthesis of the 15-year results of a collaborative program between the Johns Hopkins Medical Institutions and an African-American community with the highest rates of premature disease and death in Maryland. The program began with an efficacious disease prevention clinical trial with patients and ended with effective population approaches. We transferred key components to community ownership and formally trained community health workers who provided health promotion counseling, monitoring, linkage, and referral services. Results indicated significant decreases in morbidity and mortality as a result of improved control of hypertension. This program has begun to decrease the health status gap in an African-American population and has demonstrated long-term sustainability. Current joint activities are directed at several major causes of excess morbidity and mortality, including smoking, obesity, hyperlipidemia, and hypertension, and at plans for programs to control diabetes, substance abuse, and breast and cervical cancer. PMID- 1419135 TI - Commentary: women, research, and the National Institutes of Health. PMID- 1419136 TI - Questions on cholesterol screening study. PMID- 1419137 TI - Questions on cholesterol screening study. PMID- 1419138 TI - Focal and diffuse benign hepatic disease: correlative imaging. AB - With the large numbers of screening CT scans and ultrasounds performed in a busy radiologic practice, it is not uncommon to discover an unexpected focal or diffuse process in the liver. When there is no history of primary malignancy, many of these lesions are benign. We discuss the variety of benign focal and diffuse diseases that can be readily imaged within the liver using ultrasound, CT, and MR. PMID- 1419139 TI - Correlative imaging of malignant liver tumors. AB - Radiologists play a vital role in the management of malignant liver disease, both by providing accurate data regarding extent and segmental localization of lesions as well as demonstrating their relationship to major vascular structures. The interrelationship between the major cross-sectional imaging modalities (ultrasound, CT, and MRI) must be understood in order to use each modality effectively and efficiently. Characteristic behavior of certain tumors (such as venous invasion by hepatomas) can help in recognition of tumor type and may have a major impact on decisions regarding resectability. Pitfalls in liver imaging (such as the presence of benign conditions that may mimic malignant lesions) must be well understood in order to avoid errors in diagnosis. Difficulties may arise in underdetection of tumors arising in chronically diseased livers and overstatement of the extent of tumors in livers with coexistent benign and malignant lesions. The appearances and behavior of primary and metastatic liver cancer is reviewed, emphasizing the features listed previously. PMID- 1419140 TI - Spectral and color Doppler sonography. AB - Color Doppler sonography has become an integral part of modern hepatic sonography. Color Doppler can enhance the conspicuity of focal lesions and bile ducts in jaundiced patients by illuminating normal vessels with flow. Spectral and color Doppler may prove useful in limiting the sonographic differential diagnosis of focal liver lesions. Color flow sonography effectively evaluates pseudoaneurysms, A-V fistulae, collaterals, and flow reversal in portal hypertension, venous clot and tumor invasion, Budd-Chiari syndrome, hereditary hemorrhagic telangiectasis, and many other hepatic vascular lesions. We have found it invaluable in evaluating cirrhotic and liver transplant patients. PMID- 1419141 TI - MR angiography of the liver. AB - Recently, several versatile techniques have been developed for performing magnetic resonance (MR) angiography in the body. Relative to MR angiography in the head and neck, these methods require more interactive involvement by a physician to derive their full benefit, but they show great promise in the clinical workup of several vascular problems relating to the liver. This article outlines practical clinical applications for MR angiography of the liver, based on the experience of the authors and others working in the field. PMID- 1419142 TI - Noninvasive liver imaging: new techniques and practical strategies. AB - The goals and expectations of liver imaging have expanded as the treatment options for a range of liver diseases have advanced. Unfortunately, no single modality can yet achieve all the goals that an ideal imaging modality should satisfy. Currently available liver imaging techniques should be considered complementary rather than competitive in their roles, and appropriate utilization of the expanding technical capabilities of cross-sectional imaging depends on many considerations, including patient factors, referring physician expectations and biases, experience and bias of the radiologist, and the availability of state of-the-art technical capabilities for each modality. This article reviews the advantages, limitations, and roles of fast CT and fast MR liver imaging techniques as well as the complimentary role of ultrasound, and the future of new imaging considerations including the role of contrast agents. PMID- 1419143 TI - Cross-sectional imaging of liver transplantation. AB - Orthotopic liver transplantation is commonly performed at many institutions around the world. The care of these critically ill patients has heavily relied upon cross-sectional imaging. CT, MRI, and ultrasound help enormously in the preoperative assessment of these patients and in the postoperative management of the various complications. This article reviews the role of these cross-sectional modalities and their respective strengths and weaknesses in the adult transplant candidate and recipient. PMID- 1419144 TI - Occurrence of the purine nucleotide cycle in rat pancreatic islets. AB - The presence of the purine nucleotide cycle is investigated in rat pancreatic islets. Adenylosuccinase, adenylate deaminase, and adenylosuccinate synthetase activities are characterized in islet homogenates. In the assay of the latter enzyme, evidence is obtained for operation of the full cycle in islet extracts. The activities of the three enzymes are not vastly different in islet and brain. These findings are discussed in the light of the role currently ascribed to the purine nucleotide cycle in producing ammonia from amino acids, in adjusting the concentration of Krebs cycle intermediates, in regulating the relative concentrations of ATP, ADP, and AMP, and in controlling the activity of phosphofructokinase. PMID- 1419145 TI - Glycoprotein metabolism in neuronal ceroid lipofuscinosis fibroblasts. AB - Human skin fibroblast lines of the infantile form of neuronal ceroid lipofuscinosis and control lines were cultured in the presence of [3H]glucosamine plus [3H]mannose and [35S]methionine. The labeled glycoconjugates were compared by quantitative polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The infantile form of the disease showed a 75% decrease of four glycoprotein components of M(r) 120-140 kDa. These components appeared to be N-linked glycoproteins as peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine amidase (PNGase F) released 86-96% of the labeled carbohydrate from the labeled protein. These results suggest that the infantile form of this disease may be characterized by abnormalities in glycoconjugate metabolism leading to reduction of specific glycoproteins. PMID- 1419146 TI - Lack of hormonal stimulation of pyridoxine metabolism in isolated rat hepatocytes. AB - Isolated hepatocytes obtained from Sprague-Dawley rats (145-175 g) were incubated for 15 min at 30 degrees C in Krebs-Henseleit bicarbonate buffer, pH 7.4, containing 0.5 mM concentration of each of the 20 natural amino acids and either 4.5 or 23 microM [U-14C]pyridoxine. Pyridoxine, pyridoxal, pyridoxal phosphate, and pyridoxic acid separated by an anion-exchange chromatographic technique were quantified using a phosphate analyzer and a liquid scintillation counter. The conversion of [U-14C]pyridoxine to its metabolites was more than doubled by increasing the amount of pyridoxine (4.5 to 23 microM) in the incubation medium. Insulin (10 mU/ml), glucagon (1 nM), or epinephrine (10 microM) did not have any significant effect on the conversion of [14C]-pyridoxine to pyridoxal, pyridoxal phosphate, or pyridoxic acid. Our earlier observations of a large decrease in serum pyridoxal phosphate in the diabetic rat cannot be explained by any direct hormonal effects on pyridoxine metabolism. PMID- 1419147 TI - Biosynthesis and characterization of (S)-and (R)-3-hydroxy-3-methylglutaryl coenzyme A. AB - (S)-3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), the physiologic substrate of HMG-CoA reductase and of HMG-CoA lyase, is available commercially only as (R,S) HMG-CoA, a mixture of diastereomers. To provide (S)-HMG-CoA for our continuing investigation of HMG-CoA reductase, we used homogeneous, overexpressed Pseudomonas mevalonii HMG-CoA reductase (EC 1.1.1.88) and an NAD(+)-regenerating system to convert (R)-mevalonate to (S)-HMG-CoA with an overall yield in excess of 50%. We also used P. mevalonii HMG-CoA lyase (EC 4.1.3.4) to prepare (R)-HMG CoA from (R,S)-HMG-CoA. Each diastereomer was then isolated by ion-exchange chromatography. Large-scale preparations provide for economical production of (S) HMG-CoA, particularly when recovered coenzyme A is recycled. (S)-HMG-CoA was evaluated as a substrate, and (R)-HMG-CoA as an inhibitor, for the P. mevalonii enzymes HMG-CoA reductase and HMG-CoA lyase, and for Syrian hamster HMG-CoA reductase (EC 1.1.1.34). For both HMG-CoA reductases, (R)-HMG-CoA inhibited competitively with respect to (S)-HMG-CoA. The ratio Ki/Km was 0.7 +/- 0.1 and 0.6 +/- 0.2 for the bacterial and hamster enzymes, respectively. By contrast, (R) HMG-CoA did not inhibit P. mevalonii HMG-CoA lyase. PMID- 1419148 TI - Statistical analysis of the effect of cadmium and zinc on hamster teratogenesis. AB - Maternal smoking is correlated with lower average birth weights and an increase in malformations in some studies. Increased maternal cadmium levels and reduction of zinc levels in certain tissues from fetuses of women who smoke suggest a biological association during pregnancy. Zinc has a protective effect on hamster teratogenesis caused by cadmium. To determine whether this protective effect is additive or synergistic (interactive), pregnant golden Syrian hamsters were injected (iv) on Day 8 of gestation with a test solution based on maternal body weight (0.5 ml per 100 g). Five doses were given: 2 mg/kg zinc chloride, 2 mg/kg cadmium chloride, 3 mg/kg cadmium chloride, 2 mg/kg zinc chloride plus 2 mg/kg cadmium chloride, and 2 mg/kg zinc chloride plus 3 mg/kg cadmium chloride. Fifty dams were randomly placed into one of the groups, for a total of 10 pregnant dams in each group. Twenty other dams were randomly placed into untreated or saline control groups. Fetuses were recovered on Day 15 and weighed, crown-rump length was measured, and fetuses were examined for viability and external malformations. Resorptions were noted. Statistical analyses included one- and two-way nested ANOVA, and logistic regression adjusted for litter effect. Zinc's protective effect on acute cadmium embryonic/fetal toxicity and teratogenicity was confirmed. The protective effect was of the same magnitude relative to the dose dependent effect of the cadmium exposure, indicating that the effect was statistically additive and not synergistic. This suggests that the effect depends on competition of the two elements at some common binding site(s). PMID- 1419149 TI - Effect of insulin on the proline transport activity in cultured fibroblasts from patients with Werner syndrome. AB - The effect of insulin on the transport of proline has been studied in cultured fibroblasts from normal individuals, non-insulin-dependent diabetic patients, and patients with Werner syndrome. In fibroblasts from normal individuals and those with diabetes mellitus, incubation with 10(-7) M insulin resulted in more than a twofold increase in the transport rate after about 14 h incubation. In contrast, fibroblasts from patients with Werner syndrome had a markedly attenuated response to insulin, suggesting a defect in insulin action on the transport of this amino acid in Werner syndrome. PMID- 1419150 TI - Aldose reductase: congenial and injurious profiles of an enigmatic enzyme. PMID- 1419151 TI - [Ossiculoplasty: implants versus ossicles]. PMID- 1419152 TI - [Paget's disease with temporal bone involvement, hypoacusis and vertigo. Apropos a case]. AB - The Paget disease is a chronic osteodystrophy of unknown etiology, very frequent in 50 years of age and above. It's an anatomo-radiologic syndrome that sometimes, is accompanied by clinical symptoms. May be monostotic or polyostotic but never generalized. Occasionally it affects the temporal bone producing deafness, tinnitus and vertigo. We report a case with important temporal bone demineralization, deafness and vertigo. PMID- 1419153 TI - [The circadian evolution of the karyometric indices of the inner hair cells. A statistical analysis]. AB - We have realized a statistic study about "Karyometric Index" in the hair cells of the Corti organ of the albino Wistar rat [correction of guinea pig] in thirty of these animals; after in vivo fixation. The Karyometric Index variations are a good indicator of the cellular basic functional activity. Therefore we tried to clarify if the their cells are or not resembling to other cellular types with the functional circadian circles as well as if they present it or not in their basic functionalism, as they are also included in the "Endocrine Difusse System" and the "Paraneuron" concepts. PMID- 1419154 TI - [The importance of laryngeal compartmentation in the limitation of tumor extension]. AB - Histologic specimens from 75 patients with squamous cell carcinoma of the larynx treated exclusively by surgery were studied with special attention paid to the growth of the tumor in relation with the different laryngeal compartments. Some aspects traditionally admitted are discussed. The result show a not very close relation between the classic anatomic descriptions and the tumoral growing. PMID- 1419155 TI - [An analysis of the DNA content in a stage-T-1 epidermoid carcinoma of the vocal cord. The methodology and results]. AB - DNA content of tumor cells determined by flow cytometry has been correlated to biologic behavior and to prognosis for many solid tumors, but insufficient data has been accumulated for squamous cell carcinoma of the larynx. In order to know the predictive value of this parameter in the prognosis of T-1 vocal cord squamous cell carcinoma, we have studied 27 patients submitted to cordectomy. The patients outcome was followed for a minimum of five years or until death, DNA content was determined by Hedley method in paraffin-embedded sections of formalin fixed blocks in an EPICS Profile flow cytometer. 24 of these tumors were diploid (89%) and 3 aneuploid (11%). We didn't find statistical correlation between ploidy and survival, local failure or someone of the pathological parameters. PMID- 1419156 TI - [Laryngomalacia: a review of 42 cases]. AB - In the period from 1981 to 1990, in the Children's Hospital from Sevilla were performed 220 direct laryngoscopies and bronchoscopies to newborns and infants that showed as a main finding: stridor voice change or aspiration syndromes. In the 30 percent the main cause was a congenital laryngeal anomalies. Laryngomalacia is the most common congenital laryngeal anomaly with 42 cases. For it frequency, the otolaryngologist should be familiar with the clinical findings, diagnosis and actual management. PMID- 1419157 TI - [Pneumocephalus as a complication of mastoid surgery]. AB - Non-traumatic otologic diseases are a rare cause of pneumocephalus. Among them, few reports have been described whereas it occurred following oto-surgery. We present a case report of pneumocephalus in a patient who presented with CSF otorrhea, headache, disorientation, after recent mastoid radical surgery. The definite diagnosis was done by CT scan imaging. We realize a review of the literature about this subject, we describe the clinical and diagnostic features, its possible physiopathology, and its surgical management. PMID- 1419158 TI - [The nasal location of calcinosis cutis. Apropos a case]. AB - The metastatic calcifications, feasible in the renal chronic insufficiency, they are conditioned by tissular deposits of calcium. The metabolic and hormonal aetiology is inevitable. The known predilection for some tissues and organs in these calcic fixations, is gets to value the endonasal and cutaneous infrequent appearance, on this case. PMID- 1419160 TI - [Supracricoid laryngectomies with cricohyoidopexy. A clinical study of 6 cases]. AB - A prospective study was carried out in 6 patients with cancer of larynx operated between 1986 and 1988. Technical aspects for supracricoid partial laryngectomy with cricohyoidopexy are described. Indications, follow-up and complications are discussed. PMID- 1419159 TI - [Rhinoscleroma. A case report with nasal and laryngeal involvement]. AB - We present a case of rhinoscleroma that were studied in a spanish patient. The location was nasal and extranasal, appearing in the larynx. The diagnosis was established by the morphological picture. A review is given of the geographical distribution of this disease and the principal diagnostic procedures are outlined with special emphasis ou the most reliable staining methods (PAS, Gram), immunofluorescence, immunoperoxydase reactions and electron microscopic study are discussed. PMID- 1419161 TI - [A severe rhinological mycosis: mucormycosis. A report of 3 cases]. AB - Mucormycosis is a fungal infection, the most frequent form begins in the nose and the paranasal sinus and can rich the brain. It is a fulminant and often fatal disease, not well known by many specialists. The authors present three cases with positive cultures, histology and postmortem studies, drawing attention to the importance of its prompt diagnosis and aggressive treatment. PMID- 1419162 TI - [2 cases of facial osteosarcoma originating in the maxilla and mandible]. AB - Two cases of facial osteosarcoma are presented. The principal aspects of each patient are related, exposing the fundamental clinical and radiographic features. The respective bibliography is revised, considering the experience of some authors. PMID- 1419163 TI - [Acute dystonia due to neuroleptics in the treatment of vertigo: apropos 2 cases]. PMID- 1419164 TI - [Incidence and causes of neonatal seizures in the last 10 years (1981-1990)]. AB - We report the incidence of neonatal seizures in the last 10 years. Between 1981 1990, 28,925 infants were born in the Japanese Red Cross Medical Center. Very low birth-weight infants (< 1,500 g) were excluded in this study. Seizures were identified in 67 infants (0.23%) during the first 7 days of life. Seizures occurred more frequently in low-birth-weight infants (1,500-2,499 g) than in normal-birth-weight infants (> 2,499 g). Fifty-one infants (0.19%) of 27,276 normal-birth-weight infants and 16 (0.97%) of 1,649 low-birth-weight infants developed seizures. The frequency of seizures was 0.25% during the first 5 years and 0.20% during the second 5 years. In low-birth-weight group, the frequency of seizures decreased form 1.49% to 0.48% during the 5-year periods, and seizures due to post asphyxial hypoxic-ischemic encephalopathy also decreased from 0.14% to 0.06%. The decreased incidence in neonatal seizures during the last 10 years was probably achieved by the progress in intervention of low-birth-weight infants in NICU and by the obstetrical prevention of intrapartum asphyxia. PMID- 1419165 TI - [Changes in CSF tryptophan metabolite levels in infantile spasms]. AB - Cerebrospinal fluid (CSF) from 6 cases of asymptomatic infantile spasms (IS) (mean age, 6.1 months) was collected before and after treatment with adrenocorticotropic hormone (ACTH). The concentration of CSF tryptophan (TRP) metabolites was analyzed using HPLC and compared to the metabolite concentration in CSF from 10 age-matched controls (mean age, 6.7 months). Levels of CSF serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (KYN) at pretreatment were significantly lower in IS patients compared to controls (p < 0.05). In contrast, the levels of CSF 3-hydroxykynurenine (3-OHKY) before ACTH treatment were significantly higher in IS patients than in controls (p < 0.05). After the treatment, significant increases in 5-HIAA and decreases in KYN and 3 OHKY levels (p < 0.05) were observed in CSF of infants whose seizures were eliminated by ACTH. These findings suggested that the presence of seizures in IS was associated with a significant decrease in serotonergic activity, or that the turnover in the direction of 3-OHKY was altered. The possibility that elimination of seizures by ACTH might be related to decreased production of kynurenine metabolites was discussed. PMID- 1419166 TI - [A study on functional plasticity of the brain in childhood. II. Speech development and intelligence after the damage of cerebral hemisphere under 1 year of age]. AB - To investigate the functional plasticity of the brain in childhood, the speech development, the intelligence test and dichotic listening test were performed on 27 patients who had suffered from hemiplegia under 1 year of age. Among 13 patients with right hemiplegia, 7 to 24 years old, 11 patients showed a left ear dominance suggesting the lateralization of language in the right hemisphere. All 14 patients with left hemiplegia, 5 to 37 years old, showed a right ear dominance suggesting the lateralization of language in the left hemisphere. All 27 patients acquired speech function enough to converse with other people during daily life. There were no differences in speech development or intelligence scores between both groups of hemiplegia. Although there was no correlation between the speech development and the age of onset of hemiplegia, there was a correlation between the speech development and the intelligence score in both groups of hemiplegia. PMID- 1419167 TI - [A clinical study on neuron-specific enolase activities in cerebrospinal fluid of neonates]. AB - Activities of neuron-specific enolase (NSE) in the cerebrospinal fluid (CSF) were measured in 104 neonates (24 cases with CNS diseases and 80 cases without CNS diseases) aged from 0 to 27 days and 50 children without CNS diseases aged 3 months to 15 years. They were determined by using the radioimmunoassay of the Eiken Kit. The enzyme activity in neonates without CNS diseases was significantly higher than that in children. No significant correlation was found between the level of NSE activity and gestational age, birth weight or the days after birth. The mean level of NSE activity in the CSF of neonates with CNS diseases was significantly higher than that of neonates without CNS diseases. Those activities gradually decreased with the clinical course. It was considered that the appropriate cut-off level of NSE activities in CSF for anticipating CNS damage and neurological sequelae was 20.0 ng/ml. PMID- 1419168 TI - [Correlation between morphological abnormalities of Chiari malformation and evoked potentials]. AB - We studied correlation between morphological abnormalities of Chiari malformation and evoked potentials (short-latency somatosensory evoked potential [SSEP] and auditory brainstem response [ABR]). On SSEP the inter-peak latency prolongation of P3-N1 was revealed in 6 out of 8 cases with Chiari malformations. The feature of positive wave between P3 and N1 was divided into 2 groups. The tendency of the positivity between P3 and N1 was more marked in cases of prolonged P3-N1 latency and correlated with the medullary kink. On ABR the prolongation of III-V inter peak latency was revealed in one side in 3 patients Chiari malformations with malformed pons and tegmentum. PMID- 1419169 TI - [Maternal hyperthermia during pregnancy in severely multi-disabled children]. AB - In a study of prenatal etiologic factors for 5,901 severely multi-disabled children (jushoji as called in Japan), 159 patients were found to have been exposed to maternal febrile illnesses in utero. Among them, 57 patients did not have any causative factors other than maternal febrile illness. In addition to severe brain dysfunction, nonspecific anomalies were found in 46.2% of 26 children exposed to maternal hyperthermia before 4 months of gestation. The recent findings of other investigators tend to support the concept of unusual hyperthermia being teratogenic in human. Our retrospective study suggested that maternal hyperthermia might induce severe brain damage of embryo, but no definite malformation complex could be determined. PMID- 1419170 TI - [The study of mismatch negativity]. AB - We studied age related correlations of mismatch negativity (MMN) auditory event related potentials (ERPs) using odd ball paradigm in 121 normal subjects (from 6 months to 43 years) and 33 mentally retarded subjects (from 2 to 18 years). The subject was instructed to read a book in order to ignore the stimulus during the experiment, or no specific task was imposed on young child. The MMN wave form was clearly obtained in normal 6 month old subjects. As the age advanced from 6 months, the latencies of MMN progressively shortened till about 7 years, when the latency reached adult level. One-third of mentally retarded patients had prolonged MMN than that normal age-matched subjects. Reliable recording of P300 requires subject's cooperation and attentiveness, which are difficult to achieve in young children or mentally retarded patients. MMN may be utilized in children to evaluate the development of the cognitive function. PMID- 1419171 TI - [Neonatal tuberous sclerosis: report of a case studied by cranial MRI]. AB - We reported longitudinal cranial MRI studies of a neonate with tuberous sclerosis who presented convulsive seizures on the first day after birth. Cortical tubers were not detected on MRI performed at the age of 1 month, but became evident at 18 months after birth. This finding might reflect the pathological difference between the amount of myelin around the cortical tuber and other white matter lesions, which increased with age. A heterotopic islet was shown as partially stratiform appearance on MRI. This result suggests that the structure of the heterotopic islet might be heterogeneous. PMID- 1419172 TI - [A case of neonatal tuberous sclerosis with large calcified lesions in the brain parenchyma]. AB - A patient was reported, who was diagnosed as having tuberous sclerosis in neonatal period. He began to have complex partial seizures at 3 weeks of age. At 27 days of age, brain CT revealed a large high density lesion from the left temporal cortex to the left posterior horn, in addition to periventricular nodules. These lesions were not enhanced after injection of contrast medium. Brain MRI demonstrated more nodular lesions, the intensity pattern of which was different form those in previously reported cases. Ictal EEG showed secondary generalization from left temporal focus, which was compatible with complex partial seizures. In English literature, neonatal cases of tuberous sclerosis with large parenchymal lesions on brain CT were reported by only a few authors, and only two cases of neonatal MRI findings were documented. The neonate with tuberous sclerosis should be carefully evaluated because of the atypical appearance of MRI in rare cases. PMID- 1419173 TI - [Benign familial neonatal convulsions in a family with one member with infantile spasms]. AB - A pedigree of benign familial neonatal convulsions (BFNC) was reported. Seven members of two generations experienced convulsions in the neonatal period and/or in early infancy. All of these members except one had a good prognosis. One member who had infantile spasms was uneventfully delivered at 37 weeks of gestation, with a birth weight of 2,562 g and, without trouble during pregnancy. At the age of 20 days, she began to have adversive seizures. Later, she developed complex partial seizures and infantile spasms at 1 month and 10 days of age. Interictal EEG showed hypsarrhythmia. Biochemical investigations and MRI of the head revealed no abnormality. Treatment with sodium valproate and carbamazepine succeeded in stopping the seizures and she had no seizures after 3 months. But her psychomotor development was moderately delayed at 8 months. No case with severe epilepsy such as infantile spasms has been reported in the previous literature on BFNC. From our experience, early treatment and careful follow-up are considered to be important for BFNC. PMID- 1419174 TI - [A case of Fahr's disease accompanied with persistent vitreous artery]. AB - Serial imaging studies in a 16-year-old female affected by Fahr's disease accompanied with persistent vitreous artery were performed. She suffered from chronic subdural hematoma, which was re-moved at the age of 5 months. Brain CT scan performed at the age of 4 revealed calcified lesions at the corticomedullary junctions in the frontal lobes of cerebrum. Yearly repeated CT scans revealed an increasing number of the calcified lesions, which were observed at the cortico medullary junction of cerebrum, globus pallidus, thalami and dentate nuclei of the cerebellum. Calcifications have not increased in the last 4 years. Laboratory examinations of serum and urine failed to prove any abnormalities. She also had bilateral persistent vitreous arteries. The combination of these rare two diseases may have occurred coincidentally, but there is a possibility that the capillary dysfunction played a role in the pathogenesis of two diseases. PMID- 1419175 TI - [The first case of infantile type neuronal ceroid-lipofuscinosis in Japan]. AB - We reported the first case of typical infantile-type neuronal ceroid lipofuscinosis (INCL) in Japan. The patient was a 1-year-old girl presenting with rapidly progressive psychomotor deterioration and blindness. Muscular hypotonia, microcephaly and myoclonic jerks became marked with the progression of her disease. Diminution in amplitude of EEG, VEP and ERG was prominent in the initial stage, but ABR was normal. MRI showed progressive brain atrophy. Electron microscopic examination of the biopsied skin revealed granular matrix, the specific inclusion bodies, in the epithelial cell of sweet glands. Many sea-blue histiocytes were demonstrated in her bone marrow samples. INCL is a common progressive encephalopathy in the Scandinavian countries, but a typical case had not yet been fully reported in Japan. This prompted us to report our case. Future reports are need for the study of INCL in Japan. PMID- 1419176 TI - [Muscle cultures and immunocytochemical study of dystrophin in patients with Duchenne muscular dystrophy and control patients]. PMID- 1419177 TI - [When is the deep tendon reflex elicited in Fisher syndrome?]. PMID- 1419178 TI - [Changes in nuclear DNA content in nasopharyngeal epithelium]. AB - The nuclear DNA content was measured by flow cytometry (FCM) in 167 specimens with normal nasopharyngeal epithelium, paracarcinoma tissue and nasopharyngeal carcinoma (NPC). Thirty eight (38%) of 101 NPC, seven (58%) of 12 recurrent and six (30%) of 20 paracarcinoma tissues were nondiploid. There was no nondiploid at all in 20 specimens of normal nasopharyngeal epithelium. Two of six patients with VCA-IGA(+) were nondiploid. Cellular proliferation index (PI) of NPC was increased significantly as compared with that of the normal epithelium (P < 0.01). However there was no marked difference in PI. between NPC and paracarcinoma tissues. The rate of cervical metastasis in nondiploid NPC was significantly higher than that in diploid NPC (P < 0.025). But there was no correlation of DNA content between the stage of the tumor and the titer of VCA IGA. These data show that FCM may prove useful in the diagnosis and predication of prognosis in NPC. PMID- 1419179 TI - [Immunohistochemical distribution and fine localization of the gamma-aminobutyric acid in the organ of Corti of normal guinea pigs]. AB - This paper presents the distribution and fine localization of the gamma aminobutyric acid (GABA) in the Corti's organ of normal guinea pigs by using immunohistochemical technique (ABC-GDN method) and immunoelectron microscopy. GABA-IR was found in axons of efferent neurons in all turns of the cochlear spiral, but no positive endings may be found in the apical. The positive immunoreactive products were seen in the efferent components, including inner spiral bundle, tunnel spiral bundle, tunnel-crossing fibers, and large nerve endings on outer hair cell bases. Some of the GABA-IR negative outer hair cells could be seen between the positive endings. One GABA-IR positive nerve fiber could form synapse with six or seven outer hair cell bases. The GABA-IR positive efferent endings, negative efferent endings and negative afferent endings could be seen on the out hair cell bases with transmission electronic microscope. The GABA-IR positive efferent endings and negative afferent endings could form the neuraxon-neurodendron synapse on the inner hair cells bases. These morphological distribution suggests that the GABA may be one of the cochlear efferent neurotransmitter or modulator. PMID- 1419180 TI - [Effects of furosemide on endocochlear potentials, auditory action potentials and summating potentials and the changes of inner ear pathology]. AB - Guinea pigs were injected with furosemide 50 mg/kg (group A) and 25mg/kg (group B). Two minutes after injection, EP of group A decreased to -13.9mv while that of group B decreased to +65 mv. Also, AP of group A disappeared, and recovered at 8.5 mins. while AP amplitude of group B decreased to 78%. The SP value of group A changed from -14.5mv to +23.4mv 1 min after injection and returned to negative polarity in 12 min. Edema of stria vascularis was observed under light microscope. Transmission electron microscope showed edema between marginal cells and intermedia cells, cytoplasm of the marginal cell protruded to the cochlear duct, and cell membrane of outer hair cell folded. The finding of this study illustrates that furosemide inhibits the transportation of the active ions of cochlear duct tissue resulting in decrease of EP and alters the function of hair cells causing the change of AP amplitude. -SP depends on the ion transportation, the polarity can be inversed while large dosage of furosemide was used. PMID- 1419181 TI - [Prevention of noise induced hearing loss in musicians of Chinese opera]. AB - The incidence of hearing impairment in musicians of Chinese opera is higher than that in popular music and rock and roll music. The sound levels of different instruments used in Chinese opera measured acoustically showed drums, gongs and cymbols to be hazardous to the ear. The conventional measures of prevention, such as ear plugs are not acceptable by the musicians because of interference to the musician's hearing ability. A rearrangement of situations of the musicians was suggested by the authors. The percussive musicians should be situated one meter lower than other musicians. Animal (guinea pigs) experiments by study of AP in EcochG and ultrastructural observations of the cochlea have confirmed that our suggestion for prevention of noise induced hearing impairment to be efficient. PMID- 1419182 TI - [Topographic mapping of the auditory evoked potentials. I. Auditory cortex response and middle latency response]. AB - Color imaging of the human auditory cortex response and middle latency response of 21 otologically normal young adults was studied. All the waveforms, latencies, amplitudes and the location of FNa, FPa, FN1, FP2 were analysed. Considerable variations about the foci location in normal adults were found in this study. PMID- 1419183 TI - [Determinations of nasal effective cross-sectional area in 1100 normal subjects]. AB - Generally speaking, the NECA represents the narrowest site of the nasal airway and mirrors the site of the nasal valve in normal subjects. So the NECA is the basic element in producing and determining the NAR. A flow-pressure technique with software was developed to measure the NECA in 1100 normal subjects. The normal values values of NECA in children and adults were established to be 0.40 +/- 0.12cm2 and 0.52 +/- 0.17cm2 respectively. There was a significant positive correlation between the age increase and NECA augmentation in children (r = 0.649, P < 0.01), and NECA grew at a rate of 0.022 cm2 per year from 5 to 16 years of age, but revealed some peculiar characters in different phases of pediatric development. From 20 years of age the change of NECA began to take a stable course, but had a trend to crawl up with ageing. There were no significant differences of NECA between the male and female in different age groups. It was also noted that there was a negative linear relationship between ipsilateral NECA and NAR, and also so between the NECA of both sides combined and total NAR. From the findings above, we propose that NECA could be a quantitative and objective parameter for assessing the nasal airway impairment. PMID- 1419184 TI - [Transnasal endoscopic surgery]. AB - We have performed operations of transnasal endoscopic surgery successfully. This study was intended to analyze and discuss the method of operation on the ostium meatus unit, the removal of polyps in sphenoethmoidal recess or superior turbinate and our viewpoint of ethmoid sinus operation. We conclude that (1) the 70 degree nasal endoscope is the main instrument in endoscopy; (2) an endoscope and a head lamp should be used alternatively in order to proceed the operation quickly and smoothly; (3) the bone wall should not be broken rashly and a good drainage should be the main purpose in ethmoid sinus operation; (4) a bipolar electrical coagulator, a laser and other techniques should be used to make operative fields clear. PMID- 1419185 TI - [Aorto-esophageal fistula caused by swallowed foreign body (report of 17 cases)]. AB - Seventeen cases of aorto-esophageal fistula (AEF) induced by foreign bodies (Fb) were reported. Ingested fish and chicken bones were the most frequent offending agents (15 cases). The objects were lodged at the level of the aortic arch. It is those arrested in this region that may penetrate the esophageal wall and cause an AEF. The average latent period between the time of swallowing the FB and the signal of hemorrhage was about 8 days. A signal of hemorrhage preceding the exsanguinating episodes had been present in 14 cases. This can be taken as the indication for urgent operation. Early diagnosis of AEF can be made by the history alone, Esophagoscopy may invite a sudden death from massive hemorrhage once an AEF is already present. In a small number of cases, an aortic false aneurysm or an esophago-bronchial fistula can produce respiratory symptoms without hematemesis, Mediastinal widening on chest X-ray films usually suggests a false aneurysm but it must be differentiated from a mediastinal abscess or a tumor mass. Of these 17 patients, 11 were treated conservatively and all died. Six patients were treated surgically with 5 deaths and one surgical survivor. This case is believed to be the third reported surgical survival. PMID- 1419187 TI - [Techniques for isolating hair cells from guinea pig cochlea]. AB - Isolated live hair cells are important models for studying the electrophysiology, pathology and pharmacology of the hair cell. Using mechanical isolation method after papain treatment 70 +/- 27 hair cells, including 0 to 4 inner hair cells, could be obtained from each cochlea of 4 guinea pigs. The criteria for a good viability of isolated cochlear hair cells were: 1. a smooth hair cell membrane; 2. hair cells not swollen; 3. the nucleus in the normal position; 4. the cytoplasm in a state of semitransparency with a halo at the periphery (birefringence) and 5. no Brownian movement of the organelles within the cytoplasm. With short-term culturing at room temperature, approximately 90% of the isolated hair cells retained a good viability at the end of two hours. Subsequently the hair cells gradually degenerated but still, at the end of five hours, about 40% of them appeared intact. The degeneration patterns have been carefully observed and described. PMID- 1419186 TI - [Scanning electron microscopic observations on the middle ear mucosa of human fetuses]. AB - The epithelial development of middle ear mucosa in nine human fetuses, ranging from the 12th week to full term, was observed by the scanning electron microscopy. The results showed that the ciliated cells were found in the tympanic cleft of the 12th week fetus. The ciliated cells were especially dense in a crescent region along the antero-inferior periphery of the inner surface of eardrum, and were distributed around the tympanic orifice predominantly, above and blow the promontory and the hypotympanum. The length of cilia and the population of the ciliated cells increased with the fetal age. At the 26th week, the ciliated cell population and the length of cilia were similar to those of the neonate. The goblet cells appeared at the 26th fetal week. The secretory phenomenon of the goblet cells was seen at the 34th fetal age. These findings indicated that the mucociliary transportation system has been developed well at the late period of fetal development. PMID- 1419188 TI - [Changes in vascular stria after blast traumatized guinea pigs by colloidal lanthanum tracing technique]. AB - The exudation of endotheliocyte in the capillary vessels of vascular stria after blast traumatized guinea pigs was studied by colloidal lanthanum tracing technique. The high density lanthanum ion shown as a line--distribution can be found in the endothelial surfaces of vascular stria by using transmission electron microscopy, but nolanthanum granulars were seen in the cytoplasm of endotheliocyte, the base membrane, and the tissular interval of vascular stria. At six hours after exposure to impulse noise, the lanthanum ion can exudate to the base membrane of capillary vessels through the closed-linkup between two endotheliocytes. On twelve hours after exposure, the exudation of the vascular endothelial cell membrane was increased and the lanthanum ion of the high electronic density was precipitated to the inside of cytoplasm. This study suggested that the impulse noise may have a obvious early effect on the exudation of vascular stria and the colloidal lanthanum tracing technique is a better method in studying the cochlear microcirculation. PMID- 1419189 TI - [Establishment of immunofluorescence for the testing serum antibodies against inner ear tissues and its clinical application]. AB - A modified Sainte-Marie technique for processing the inner ear tissues of guinea pigs was described in this paper. The inner ears were fixed over night in 95% cold ethanol, decalcified 7-10 days in 10% EDTA-Na2 at 4 degrees C, and embedded in paraffin. The deparaffinized sections were exposed 15 min in 95% ethanol precooled to 4 degrees C to fix the serum antibodies of patients and labeled antibody respectively. The sections were counterstained with Evans-blue. This method is simple, rapid, and sensitive, and antigenicity. Also, the specificity was enhanced and the preservation of fluorescence was prolonged. By means of this method, antibodies against inner ear tissue were found in the serum of 18 out of 30 patients with Meniere's disease, sudden deafness or uncertain forms of progressive sensorineural hearing loss. The results suggest that autoimmune response may play an important role in some inner ear disease. PMID- 1419190 TI - [Intraoperative monitoring auditory function during surgery of internal auditory canal and C-P angle]. AB - Intraoperative measurement of electrocochleography, auditory brainstem responses and eighth nerve action potentials are utilized to assess the functional integrity of the cochlea and cochlear nerve. All such assessments have only one purpose: for warning the surgeon the possibility of damage the auditory system or its surrounding structure. Eighteen patients with various otoneurological diseases undergoing surgery had intraoperative monitoring of such evoked electrophysiological responses. Hearing was preserved in sixteen patients. However, the CM/N1 in ECochG still keep for a few minutes even after transection of the cochlear nerve and there is another disadvantage of need for signal averaging in BAER. Recording of the response of the the auditory nerve directly from the eighth nerve provides the surgeon with immediate information when an insult has been made to the cochlear and eighth nerve. Therefore, combination of these three measurements are recommended depending on the situation. PMID- 1419191 TI - [Revision stapedectomy]. AB - Early and delayed complications in the inner or middle ear may follow stapedectomy and require revision surgery. The records of 72 patients who had undergone revision stapedectomy were analyzed to determine: 1. the causes of failure. 2. how to revise the conditions due to the failure following previous operation. 3. hearing results. These 72 revision operations consisted of 66 case of conductive deafness and 6 sensorineural loss. The commonest cause of failure was dysfunction of prosthesis (23.6 per cent), followed by otosclerotic regrowth (22.2 per cent), incus dislocation (13.9 per cent), reparative granuloma (12.5 per cent), incus necrosis (11.1 per cent), and fibrous adhesions (9.7 per cent). A review of these cases demonstrates that the results of revision stapedectomy are different from those for primary stapedectomy. The revision operations resulted in post-operative air-born gaps of 15 dB or less in 39.4 per cent of cases. Primary stapedectomy resulted in successful closure of the air-bone gap to 15 dB or less in 97.2 per cent of cases. 'Dead ears' were encountered in 9.1 per cent as against 2.1 per cent in the primary cases. Thus the surgeon should be aware of the problems and risks involved in revision stapedectomy. PMID- 1419192 TI - [The reconstruction of upper alimentary tract after resection of hypopharyngeal and cervical esophageal cancer]. AB - The most difficult problem during surgical treatment in the hypopharyngeal and cervical esophageal cancer is the reconstruction of upper alimentary tract after resection of the lesions. From April 1984 to October 1990, 52 patients of hypopharyngeal and cervical esophageal cancer were treated by surgery (39 men and 13 women). The age ranged 43-73 years. All of the cases were squamous cell carcinoma except one adenocarcinoma. The pectoralis major myocutaneous flap (PMF) was used in 32 patients, total gastric transposition (GT) in 15 patients, free jejunal interposition (FJI) in 3 patients and free forearm flap (FFF) in 2 patients. Results showed that satisfactory and lasting deglutatory function was achieved in 48 of 52 patients (92.3%). One and three-year survival rates were 86.2% and 65% respectively. These data showed that reconstructive method described above are effective and reliable. PMID- 1419193 TI - [Comparison of diagnostic value between the parameters of auditory brain stem response in 48 patients with retrocochlear lesions]. AB - This study was done for comparing the diagnosing value between some parameters of the time and frequency domain analysis of ABR in 48 patients with retro-cochlear lesions which were identified by CT and/or surgical, pathological examination. In conclusions, it revealed that the abnormalities of wave I-VIPL and delta V value could be the most sensitive and reliable index; the changes of AR spectrum and III-V/I-IIIIPL ratio could be the assist one. Combined with the ILD and difference between bilateral I-VIPL, must be useful for determining the location of retro-cochlear lesions. PMID- 1419194 TI - [Vascular relationships of the trigeminal root with trigeminal neuralgia]. AB - The vascular relationships of 79 trigeminal nerves exposed surgically for treatment of trigeminal neuralgia were studied. 87 etiologic vessels (vein in 28, artery in 59) were found and the most common arterial and venous etiologic vessel was the superior cerebellar artery (33/59) and petrous vein (16/28) respectively. The result provided some clinic data for microvascular decompression in treatment of idiopathic trigeminal neuralgia. PMID- 1419195 TI - [Traumatic orbital wall fracture]. AB - Thirteen patients with orbital wall fracture by trauma were reported. Among them, 6 cases were inferior-wall type, another 6 cases were interioinferior-wall type, and 1 case with interior-wall type. The clinical manifestation was mainly enophthalmos. All of patients were treated with plastic operation through nasal sinuses and fixed with national osseous cement. 11 cases were cured, 1 case was improved, 1 case had no change. PMID- 1419197 TI - [Advances in the research of motility of cochlear outer hair cells in vitro]. PMID- 1419196 TI - [Diagnostic value of stroboscopy in early glottic carcinoma]. AB - Stroboscopic evaluation was conducted on 34 cases with glottic T1 carcinomas, and the relationship was studied between the area, thickness and volume of the lesion and the amplitude as well as mucosal wave of vibration. In all cases the mucosal wave of the lesion (WAVL) was abolished. The amplitude of the lesion (AMPL) was decreased in 17 and abolished in another 17 cases. There were significant relationship between the area of the lesion and the mucosal wave of the entire vocal fold (WAVE), the thickness of the lesion and AMPL, and the volume of the lesion and WAVE, AMPL, and the amplitude of the entire vocal fold (AMPE). The present paper suggested that if WAVL is reserved, the lesion is not invasive carcinoma, nor is it if any one of AMPE, AMPL, WAVE or WAVL is normal (except for lesions confined to the cartigenous vocal fold). PMID- 1419198 TI - Who cares for your dementia? PMID- 1419199 TI - Zoonoses of slaughterhouse workers. PMID- 1419200 TI - Membership of the Faculty of Public Health Medicine: the new Part I examination. PMID- 1419201 TI - The measurement of patient satisfaction. AB - Many applied health service researchers launch into patient satisfaction surveys without realizing the complexity of the task. This paper identifies the difficulties involved in executing patient satisfaction surveys. The recent revival of interest in 'satisfaction' and disagreements over the meaningfulness of a unitary concept itself are outlined, and the various perspectives and definitions of the components of satisfaction are explored. The difficulties of developing a comprehensive conceptual model are considered, and the issues involved in designing patient satisfaction surveys--and the disasters that occur when these issues are ignored--are then set out. The potential cost-effectiveness of qualitative techniques is discussed, and the paper concludes by discussing how health care management systems could more effectively absorb the findings of patient satisfaction surveys. PMID- 1419202 TI - Discounting in health care decision-making: time for a change? AB - Economic appraisal is increasingly being used to inform health care decision making. To allow comparison, costs and benefits spread over time are weighted according to when they are experienced. The further in the future, the less heavily they are weighted or the more they are discounted. Traditional economic appraisal techniques are based on the view that social decisions should reflect private preferences. The practice of discounting future streams of costs and benefits is principally justified by the fact that individuals have a positive time preference, preferring consumption sooner rather than later. Discounting weights public decision-making in favour of interventions resulting in short-term benefits and against longer-term benefits. This discriminates against preventive and other public health programmes. This paper provides a critique of the foundations of discounting. It is argued that health policy should have a longer time horizon, reflecting social values rather than individual preferences. Factors which make discounting the future rational from the individual's point of view are shown to be irrelevant to a societal perspective. Although uncertainty about the effectiveness of interventions and technological change are good reasons for weighting some future benefits less highly, the routine use of a single discount rate for economic evaluations of health programmes is not justified. PMID- 1419203 TI - An evaluation of population screening for carriers of cystic fibrosis. PMID- 1419204 TI - A comparison of prospective and retrospective diary methods of assessing alcohol use among university undergraduates. AB - The objective of this study is to compare data about the quantity of alcohol consumed by university undergraduates using a prospective diary with those data collected using a retrospective diary. Five hundred and ninety-eight subjects were randomly selected and divided into two groups matched for age, sex, year of study and subject group; one group received a prospective and one a retrospective questionnaire-301 students received prospective and 297 retrospective questionnaires. Sixty-eight per cent responded to the prospective and 75 per cent to the retrospective survey. There was no significant difference in the median alcohol consumption detected for men or women in this study (p = 0.13; p = 0.47). However, the prospective diary recorded a greater proportion of heavy drinkers, this difference being significant for men and women (p less than 0.05). The quantitative results of the retrospective diary are similar to those obtained by a similar method in a previous survey. The conclusion is that a prospective diary detects a greater proportion of heavy drinkers than a retrospective diary. The prospective survey may be the most appropriate method for assessing alcohol use in certain situations. PMID- 1419205 TI - Quality of hospital service: a study comparing 'Asian' and 'non-Asian' patients in Middlesbrough. AB - To compare 'Asian' and 'non-Asian' patients' experience of and satisfaction with non-clinical aspects of their hospital care, and to evaluate the effect of subsequent provision of 'Asian' food, we undertook interview surveys of recently discharged adult patients in Middlesbrough. Fifty-two 'Asians' and 52 'non Asians' matched for sex, age, specialty of admission and hospital reported similar experiences in regard to the amount of information received, the presence of medical students during examination, and satisfaction with privacy and visiting arrangements. The main differences between the groups related to the receipt of written information in the patients' first language, 'Asian' patients' inability to communicate because of lack of English and their dissatisfaction with existing interpreting arrangements, 'Asian' women's attitudes to examination by male doctors, and provision of and satisfaction with hospital food. For example, 47 (90 per cent) 'Asians' and 14 (27 per cent) 'non-Asians' required a special diet but 19 per cent and 86 per cent, respectively, received it; and 'Asians' were less satisfied with the food overall. Despite being disadvantaged 'Asian' patients seldom complained. Following the provision of 'Asian' food, 'Asian' patients reported satisfaction levels comparable with those of 'non Asians'. Equitable health care provision for ethnic minorities requires a level of service comparable with that enjoyed by the majority community. Written information in minority languages, professional interpreters, examination of female patients by women doctors and culturally suitable food were confirmed as priority needs. Staff training and community education may ensure successful implementation of policy on health care of ethnic minorities. Finally, the quality of non-clinical care in hospital needs to be raised for all groups of patients. PMID- 1419206 TI - A geostatistical approach to the analysis of pattern in rare disease. AB - The incidences of human disease vary from place to place, and some show distinct patterns. Patterns in rare diseases, such as childhood cancer, are not readily discernible, however, and this makes it difficult to relate their distribution to factors in the environment in seeking possible causes of the disease. Provided cases are geographically indexed, data on a disease can be analysed geostatistically. Variograms can be computed to determine the strength and spatial scale of any pattern, and to summarize the variation, and then the risk of developing the disease can be estimated by kriging. This has been done for the incidence rates of childhood cancer from 1980 to 1984 in the West Midlands Health Authority Region of England. A novel modification was made to compute the variogram of the risk from that of the frequencies, taking into account the binomial nature of the data. The incidence of the disease appears patchy. The results show that this patchiness is spatially correlated and not purely random. The risk appears greatest in the rural south west of the Region and in some of the suburbs around the conurbation. This approach using geostatistics seems very promising and will be developed further as more data for this and other diseases become available. PMID- 1419207 TI - A rural advantage? Urban-rural health differences in northern England. AB - Rural health inequalities have been relatively neglected in recent years. The data assembled for a large study of health and deprivation in the Northern Region of England have been reanalysed to examine three questions. How wide are rural health inequalities compared with those in urban areas? Is health intrinsically better in rural areas, given comparable deprivation or affluence? Is the association between health and wealth weaker in rural than in urban areas? It is shown that, although health inequalities are wider in urban areas, this corresponds to wider socio-economic divisions: at equivalent levels of wealth, health measures are similar. This relationship breaks down, however, when the most remote rural areas are compared with matching localities in conurbations, for in this case rural areas have a clear advantage. We go on to show that the apparent weakness of the association between health and wealth in rural areas is largely an artefact; the association becomes stronger when the units of population (electoral wards) are enlarged to resemble more closely those in urban contexts. The comparability of rural and urban forms of deprivation is discussed in the light of these results. PMID- 1419208 TI - General practitioners, skin lesions and the new contract. AB - We reviewed all skin lesions received in our laboratory from general practitioners (GPs) during a three-month period before the introduction of the new contract for GPs and during the same period a year later. For comparison we also reviewed skin lesions received from the general and plastic surgeons. Particular attention was paid to the completeness of excision. There was a significant increase in the number of skin lesions removed in general practice after the introduction of the new contract. Both benign and malignant lesions were more likely to be incompletely excised by GPs compared with surgeons. The GPs first noted to carry out minor surgery after the new contract came into force were less likely to have completely excised lesions than their more experienced colleagues. We suggest the future monitoring of lesions removed in general practice, possibly by the formation of a joint audit group. PMID- 1419209 TI - Boneline: evaluation of an initiative to improve communication between specialists and general practitioners. AB - In response to a previous study of GPs' and consultants' satisfaction with orthopaedic outpatient referrals, orthopaedic surgeons at Doncaster Royal Infirmary made themselves available for telephone consultations with general practitioners (GPs) at advertised times. This service, called 'Boneline', was used infrequently, though the GPs who did use it found it valuable, and reported that a number of referrals had been avoided by speaking to the consultant. There was, however, no significant change in the rate at which requests for out-patient appointments were received during the six months of Boneline's operation. Opportunities for improving telephone communication between GPs and consultants are discussed. PMID- 1419210 TI - Towards the audit of geriatric day hospitals: a pilot project in west Surrey/north east Hampshire. AB - Following the recommendation of a report on the performance of two geriatric day hospitals (GDHs) in West Surrey and North East Hampshire District Health Authority in 1988, a pilot study was set up to assess the efficacy of a proposed form of audit involving multidisciplinary teams. An outcome measure which consisted of four different scales was developed and agreed upon by the multi professional team. These scales were used to work out a composite index (Patient Achievement Inventory-PAI). In addition, a new data form was designed for collection of patient data. To carry out this prospective clinical audit, targets were agreed for each patient, and progress was measured against them. Sixty-one (61) patients were studied (30 and 31 per respective hospital). Data form completion was 90 per cent and 81 per cent respectively. The PAI index proved to be reliable (kappa index of agreement = 0.72), and useful as an outcome measure. However, because the PAI index is made up of ordinal scales, it can only be used to measure change within individuals, not between them. The outcome measures, data forms and the continuous audit of these two GDHs proved to be meaningful and acceptable in practice. PMID- 1419211 TI - Quarterly communicable disease review January to March 1992. From the PHLS Communicable Disease Surveillance Centre. PMID- 1419212 TI - Study to examine the timeliness of care received by patients with open fracture of lower limb. PMID- 1419214 TI - The Health Department and research. PMID- 1419213 TI - The Health Department and research. PMID- 1419215 TI - Travel-associated hepatitis A. PMID- 1419216 TI - Low immunization uptake rates in an inner-city health district: fact or fiction? PMID- 1419217 TI - Restoration of maxillary anterior teeth using porcelain jacket crowns and porcelain veneers. AB - Combining different types of restorations when restoring maxillary anterior teeth poses a difficult esthetic problem. This article describes a method of restoring maxillary anterior teeth using a combination of porcelain jacket crowns and indirect porcelain laminate veneers. PMID- 1419218 TI - Financial considerations regarding acquisition of the Siemens Cerec computer reconstruction system. AB - There has been much interest in the in-office fabrication of ceramic posterior restorations using computer-aided design and computer-aided manufacture (CAD-CAM) units. One concern that practitioners have concerning the use of one of these systems is the initial expense of the CAD-CAM unit for the office. This article deals with the financial implications involved when considering the purchase or lease of a CEREC (CAD-CAM) unit. PMID- 1419219 TI - Changes in lip contour following treatment of maxillary protrusion with esthetic orthodontic appliances. AB - With the advent of acid etching techniques and the elimination of unesthetic band materials, direct bonding of orthodontic attachments kindled a desire for cosmetic appliances such as labial ceramic brackets and lingual orthodontics. Owing to the esthetic nature of our combination upper-lingual lower-ceramic orthodontic approach, adults who would have normally avoided orthodontic treatment are now seeking treatment. This study evaluated the cephalometric changes in the soft tissue lip profile following treatment of Class II Division 1 malocclusion with upper first bicuspid extractions with our esthetic orthodontic appliance approach. Serial lateral cephalograms (pretreatment and posttreatment) of 16 adult patients with a mean age of 22.1 +/- 3.2 years were studied. The mean upper incisor retraction, upper lip retraction, upper lip lengthening, and lower lip retraction were 5.75 +/- 1.91 mm, 2.8 +/- 1.4 mm, 1.5 +/- 0.6 mm, and 1.4 +/- 0.6 mm, respectively. All these changes were statistically significant (p < 0.01). The nasolabial angle increase of 10.8 +/- 3.0 degrees was also statistically significant (p < 0.01). The upper lip retraction to upper incisor retraction was 1:2.1, while the upper lip lengthening to upper incisor retraction was 1:3.8. The correlation coefficients (r) were 0.91 (p < 0.01) and 0.57 (p < 0.01), respectively. This study shows that significant esthetic changes in lip profile are possible with this cosmetic orthodontic appliance approach. The treatment results in this study appear comparable to those published with labial metal brackets. With very few exceptions, patients were able to adapt within 2 weeks, with almost no trauma to the tongue. PMID- 1419220 TI - Bond strength of fiber-reinforced composite resin restorations. AB - Severe tooth wear is common in older dentate individuals, with one treatment option being composite resin restorations reinforced with a suitable matrix. This study evaluated the use of high modulus polyethylene (Celanese) fibers as a reinforcing matrix for composite resin. Human mandibular incisor teeth were sectioned to simulate severe tooth wear. Sectioned surfaces were measured, the teeth paired and assigned to control or test sample groups, and further assigned to be tested with a labial or lingual shearing force. A phosphorylated dentin bonding adhesive was applied to the abraded dentin surface. Labial and lingual intra-enamel bevel preparations were cut on each specimen. A piece of Celanese fabric was bonded onto the acid-etched labial and lingual bevels of the test specimens using an enamel bonding agent. Class IV composite resin restorations were then placed onto the test and control specimens. Following water storage, the specimens were subjected to shearing forces. Bond strengths for test specimens were significantly greater (p < 0.03) than the controls. Specimens with a labially applied force also had significantly higher bond strengths (p < 0.001). SEM analysis revealed adhesive bond failures over dentin surfaces, with cohesive bond failures within the composite resin. Celanese fibers maintained the restorations on the teeth, although adhesive failures were seen between the fibers and enamel bonding agent. PMID- 1419221 TI - Conservative treatment of cervical sensitivity. PMID- 1419222 TI - Simplified occlusal anatomy for posterior composites. AB - Direct posterior composites have had problems in the past and thus have not had wide acceptance. The newest generation materials overcome many of their previous shortcomings. Finishing with proper anatomy has been difficult and time consuming. An alternative to overfilling and then grinding in the anatomy is proposed. Using a prefilled tip allows small increments of composite to be placed without flowing and sagging. Each cusp is individually shaped and initially cured for 10 seconds. Every attempt is made not to overfill the preparation to avoid unnecessary grinding. The anatomy shapes up almost automatically, similar to P.K. Thomas waxing. With only minor adjustments and polishing with a polishing paste, time spent finishing is reduced. Natural looking, functional, and beautiful occlusal anatomy is now possible with this simple technique. PMID- 1419223 TI - Pharmacokinetics of astemizole in children. AB - Astemizole is often administered to children in the treatment of rhinoconjunctivitis and urticaria with good efficacy and few side effects. Both astemizole and its major metabolite desmethylastemizole (DMA) are clinically effective without annoying side effects such as sedation. The pharmacokinetics in adults is well known. In three different studies we have investigated the pharmacokinetical properties of the drug in children. Study I (absorption): Thirty-eight children 8-16 years old (mean 12.6 years) and weighing 25-80 kg (mean 45 kg), with rhinoconjunctivitis due to birch pollinosis, were pretreated with either astemizole 5 mg daily or placebo for two weeks. Then, all children were treated with astemizole in doses increasing every week, i.e. 5, 10, 20 and 40 mg per day. There was a good correlation between the given dose per kg body weight and the plasma concentration of astemizole plus hydroxylated metabolites, indicating that astemizole is completely absorbed. Study II (time to reach steady state): A group of 21 children 7-18 years old (mean 13.9 years), plus 2 younger children, 2 and 5 years old, with allergy against birch- or grass pollen were treated with astemizole 10 mg daily for 12 weeks. Astemizole had reached steady state plasma levels when the first sample was taken after 1 week, DMA reached steady state within 4 weeks. Study III (elimination half-life [t1/2 beta]): In 10 of the children from study II, t1/2 beta for astemizole plus DMA could be calculated (two samples) and was 10.8 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419224 TI - Clinical experience with non-sedating antihistamines in paediatric allergic rhinitis. AB - This paper reviews all clinical studies involving the use of astemizole in children. The indications of seasonal allergic rhinitis, perennial rhinitis and various allergic disorders were considered in a total of 21 studies (1,008 patients). Reference compounds were placebo and other antihistamines, such as chlorpheniramine and terfenadine. Astemizole and other antihistamines were effective in the treatment of these disorders with a more favourable result for those treated with astemizole. Astemizole appeared very satisfactory as regards laboratory data and absence of side effects. PMID- 1419225 TI - Epidemiology of allergic diseases in children. AB - The one-year-prevalence rate of bronchial asthma in children varies from 1-3%, when investigated in general practice, to 5-7% in population studies. The prevalence rate is highest in young boys. Eighty percent of the asthmatic children are allergic, house-dust-mite allergy being the most common allergy. The one-year-prevalence rate of rhinitis is 5-10% in general practice, and 10-12% in population studies. Again, the prevalence rate is highest in young boys. About 90% of children with rhinitis symptoms are allergic, with pollen allergy as the most common allergy. Risk factors for developing allergic diseases are many. The predisposition is probably the most prevailing risk factor. Period of birth, sex, race, diet, the presence of other allergic diseases, tobacco smoking, pollution, and allergens in the environment, all these factors alone or in combination almost double the risk. There is no doubt that both asthma and hay-fever prevalences have steadily increased within the last 50 years. Also, admissions to hospitals for childhood asthma have continued to increase, while the mortality of asthma in children has not risen statistically. This increase is in contrast to the effective medication available for both asthma and allergic rhinitis, and to the number of preventive factors known to us today. The time has come to try to change it at all costs. The outcome of allergic rhinitis and asthma shows that only 10% are cured, 50% ameliorate, 30% remain unchanged, and 10% deteriorate. Factors determining the outcome are age, immunotherapy, sex, mother's age at childbirth, infections, other allergic diseases, and signs and symptoms of food allergy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419226 TI - [Surgical correction of double aortic arch in infants]. AB - The article generalizes the experience in the surgical correction of a rare anomaly of the aortic arch--a vascular ring in the form of a double arch of the aorta in 2 babies. In a 9-month-old baby with Fallot's tetralogy the double aortic arch was found during an operation. The child died after the operation (division of the left arch of the aorta distal to the left subclavian artery in a left descending aorta and formation of a subclavian-pulmonary anastomosis). In the other 3-month-old patient with a marked picture of tracheo-esophageal compression tracheobronchoscopy and esophagography showed a double aortic arch with predominance of the right arch, right descending aorta, and a wide patent ductus arteriosus. The operation involved division of the ductus arteriosus and the hypoplastic left aortic arch between the left common carotid and left subclavian arteries. A prolonged period of regression of the symptomatology of tracheoesophageal compression was noted in the postoperative period. Early recognition of this anomaly of the aortic arch and active surgical tactics facilitate improvement of the results. PMID- 1419227 TI - [Surgical treatment of left-atrial myxoma]. AB - The authors had 29 patients with myxomas of the left atrium under observation and treated them by operation. Three patients died after the operation. Examination of 22 patients in postoperative periods of 8 months to 15 years did not reveal recurrent tumors of the heart. The extremely rare development of tumors of the heart and the absence of specific clinical manifestations make it difficult to establish the diagnosis in time. The relatively high postoperative mortality (12%) is due, first of all, to establishment of the diagnosis during the operation as a consequence of which an emergency operation on an open heart cannot be conducted. Operative treatment is indicated for all patients with a recognized tumor of the heart. PMID- 1419228 TI - [Ventricular tachycardia: the role of adrenergic stimulation in the prognosis of fatal arrhythmia]. AB - A new method for appraising the individual efficacy of an antiarrhythmic agent is described. It is based on paired administration of isoprenaline and testing antiarrhythmics for maximum activity. The possibility of provoking ventricular tachycardia by isoprenaline made it possible to identify a contingent of patients with "catecholamine-sensitive" or "variable" tachycardia. The prognosis of "catecholamine-sensitive" ventricular tachycardia proved to be the worst in groups of patients with ischemic heart disease attended by postinfarction cardiosclerosis and in patients with arrhythmogenic dysplasia of the right ventricle. PMID- 1419229 TI - [10-year experience with correction of supraventricular tachycardia]. AB - The results of a 10-year experience in surgical treatment of supraventricular tachyarrhythmias in 258 patients are analysed. Invasive and noninvasive methods of electrophysiological studies with the predominant use of Soviet-produced apparatuses were employed in establishing the diagnosis. Surgery of arrhythmias included catheter destruction, cryosurgery on a working heart, but the prevailing methods were various types of destruction of anomalous conducting paths under conditions of extracorporeal circulation. The authors suggest a method for dosed electrocoagulation of paranodal tissues in atrioventricular nodal tachycardias. The results of the operation were positive in over 90% of cases. Three fatal outcomes in operations with extracorporeal circulation occurred during the first years of accumulation of experience in the method. It is concluded that the operation is highly effective in severe tachyarrhythmias. PMID- 1419230 TI - [Thermal condition of the myocardium in patients with ischemic heart disease during cardioplegic heart arrest]. PMID- 1419231 TI - [Additional myocardial protection by normothermic cardioplegic reperfusion]. AB - Three series of experiments were conducted on a model of an isolated working rat heart to study the efficacy of variants of cardioplegic myocardial protection in exposure to 30-minute total ischemia at 37 degrees C: (1) preischemic administration of potassium solution (K(+)-30 mM, Mg(2+)-1.6 mM, osmolarity 330 MOSM/1); ischemia, unmodified reperfusion; (2) preischemic administration of this solution, ischemia, postischemic administration of this solution for 5 minutes (normothermic cardioplegic reperfusion), putting in a working regimen; (3) the regimen of the experiments is the same as in series 2, but normothermic cardioplegic reperfusion was carried out with a modified potassium-magnesium solution (K(+)-15 mM, Mg(2+)-15 mM, osmolarity 360 MOSM/1). The values of functional restoration, rate and total discharge of the enzyme LDH into the perfusate were compared. Restoration of functional values (aortic pressure, aortic output, cardiac index) according to the experimental series: 3 greater than 2 greater than 1. LDH discharge into the perfusate: 3 less than 2 less than 1. The results of the study provide evidence that reperfusion damage may be lessened by normothermic cardioplegic reperfusion; the highest effect was produced by a solution with specially selected properties: electrolyte composition and high osmolarity. PMID- 1419232 TI - [Separation and shunting of intramyocardial segments of the coronary arteries in their proximal affection by the arteriosclerotic process]. AB - Operations for the formation of an aortocoronary shunt were performed on 395 patients in the period between October 1983 and January 1991. The anomalous position of one or more segments was found in 70 patients. The autologous vein was used as a graft in 65.7% of these patients and the internal thoracic artery in 34.3% of cases. The anterior interventricular branch (AIVB) was situated in the myocardium in 58.6% of cases and the circumflex branch (CB) in 31.4% of cases, in 8.6% of cases the segments of some arteries were situated anomalously. The AIVB was separated beginning from its segment distal in relation to its intramyocardial segment in the region of its subepicardial passage, after which an incision was made in the myocardium overlying the intramyocardial segment. The anomalously situated segments of the other coronary arteries were separated by the same techniques. In one case the AIVB was lying in the cavity, in another, it was stretched under the endocardium. After shunting these arteries were transposed to the surface of the left ventricle which allowed the ventriculotomy incision under them to be sutured. There were no complications linked with separation and shunting of intramyocardial segments of the coronary arteries. These segments of the coronary arteries have a larger lumen and are very rarely involved in an atherosclerotic process. Proceeding from the aforesaid, intramyocardial segments of coronary arteries whose proximal parts are affected by atherosclerosis must be separated and shunted. PMID- 1419233 TI - [Echocardiographic diagnosis of the origin of the aorta and pulmonary artery from the right heart ventricle]. AB - The origin of the aorta and pulmonary artery from the right ventricle is a congenital heart disease whose anatomical and echocardiographic criteria are the object of wide current discussion. The classification of the disease has been developed at the Bakulev Institute of Cardiovascular Surgery, USSR AMS. It is based on identification of the anatomical differences in the types of origin of the aorta and pulmonary artery from the right ventricle (RV OAPA). The present research was devoted to the study of the possibilities of echocardiography in the differential diagnosis of the types of the anomaly in the RV OAPA complex and the possibilities of noninvasive differential diagnosis of RV OAPA and adjacent anomalies of the conotruncus. The results of the study allow the conclusion that location of intracardiac structures with purposeful use of ultrasonic projections provides the possibility of making the differential diagnosis of the types of the anomaly in the RV OAPA complex and that the obtained echocardiographic criteria may serve for establishing the differential diagnosis of RV OAPA and other congenital anomalies of the conotruncus. PMID- 1419234 TI - [Tracheal prosthesis]. AB - A prosthesis of the authors' design with various connective elements of knitted Lavsan fabric was tested in experiments on 43 mongrel dogs. Clinical, radiological, radiospirographic, and morphological studies showed that the optimal prosthesis is that in which the connective elements are made of knitted Lavsan fabrics with an average stitch size of 20-23. Granulation tissue grows through the prosthesis which is fastened well to the connective-tissue cuff forming around it. The trachea replaced by the prosthesis ensures adequate gas exchange and lung functioning, causes no essential disorders of pulmonary volumes, ventilation and perfusion of the right and left lungs. PMID- 1419235 TI - [Mechanism of pharmacological pleurodesis with morphocycline]. PMID- 1419236 TI - [Complex evaluation of external respiratory function in patients with cancer of the lung]. AB - Principles of complex appraisal of the function of external respiration were worked out on the basis of analysis of the mechanics of respiration with the use of body plethysmography and invasive examination of pulmonary circulatory dynamics and gas transport. The suggested method allows practicable appraisal of the mechanisms of oxygen transport disorders and identification of the leading link in the development of alveolo-respiratory failure. PMID- 1419237 TI - [First results of using laser angioplasty of peripheral arteries in clinical practice]. PMID- 1419238 TI - [Place of the autologous myoneoventricle in the evolution of the methods of assisted and replacement blood circulation in critical conditions of the pumping function of the heart]. PMID- 1419239 TI - [Malignant pedicled hemangioendothelioma of the lung]. PMID- 1419241 TI - The importance of the generalist. PMID- 1419240 TI - [Triple-valve prosthesis (old problems, new prospects)]. AB - The article analyses 30 operations for prosthetics of the mitral, aortic, and tricuspid valves in patients with trivalve rheumatic heart disease. Twenty-nine patients had a marked organic tricuspid valvular disease. Various models of prostheses (ball, semispherical, biological, disk) were used for replacement of the valves. Techniques which allowed the subvalvular structures of the tricuspid valve to be preserved partly or completely were applied in 18 patients. The hospital mortality was 16.7%, long-term mortality 4%. Improvement by two functional classes and more occurred in 86% of patients. It is concluded that surgeons are no longer compelled to resort to prosthetics of the tricuspid valve, which has now become an alternative operation, particularly in the category of extremely grave patients with organic affection of 3 valves when the prognosis of the result is needed in view of the patient's severe condition. The techniques for preserving the valvular apparatus provides optimum conditions for functioning of the right ventricle in replacement of the tricuspid valve. PMID- 1419242 TI - Health promotion: time for a new philosophy? PMID- 1419243 TI - Outcome measures for primary health care: what are the research priorities? AB - A Delphi technique was used to ask general practitioners for their opinions as to which clinical problems and types of measure they thought most appropriate for the development of outcome measures for use in primary health care. The study comprised two rounds of postal questionnaires, targeted at general practitioners in academic departments throughout the United Kingdom and at trainers in the northern region, with the second questionnaire feeding back opinions from the first. Ninety eight participants suggested one or more areas in which outcome measures could be developed, giving a total of 451 suggestions. Consensus produced in the second round indicated that three clinical conditions were preferred for the development of outcome measures: asthma, diabetes and hypertension. Six categories of outcome measures were developed from the responses given in the first round--level of function, level of clinical control, incidence of complications, iatrogenic problems, patient understanding of a condition, and quality of life. Participants gave these measures different levels of importance according to the clinical problem in question. This Delphi study of doctors' opinions is a first step in the development process of appropriate, practicable measures of outcome for use in primary care and has achieved a degree of consensus among general practitioners. PMID- 1419244 TI - Problems of drug abuse, HIV and AIDS: the burden of care in one general practice. AB - Responsibility for many of the problems of intravenous drug abuse and human immunodeficiency virus (HIV) infection lies with community care agencies, such as general practitioners, community psychiatric and district nurses and drug agencies. It is in general practice that this burden is most clearly observed, given that general practitioners are in charge of the day-to-day care of patients. In an attempt to quantify this workload in an inner city practice with 11,200 patients, data were gathered from several sources relating to drug use and HIV infection. The study identified 432 patients who had consulted with problems of drug abuse and/or HIV infection over the period 1981-90. Among this group of patients 161 (37%) were HIV antibody positive. Among 191 drug abusers who were still registered with the practice in 1990 dihydrocodeine was the most commonly prescribed substitute treatment (130 patients) and only nine patients were prescribed methadone. Forty seven per cent of drug users continued to inject drugs occasionally. However, analysis of urine samples revealed that there was a shift away from injecting mainly heroin to multiple drug use, including benzodiazepines, usually originating from prescribed sources. Drug abusers who were HIV positive consulted their general practitioner significantly more often over one year than those who were not (mean 24.9 versus 15.8 consultations, P < 0.01). However, there was no significant difference between these two groups in terms of days spent in hospital. A total of 61 patients were referred to a community psychiatric nurse over an eight month period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419245 TI - Social indicators of health needs for general practice: a simpler approach. AB - The ability of different measures of socioeconomic position to predict distress in a sample of general practice attenders has been examined. Perceived distress was measured using the Nottingham health profile. The measures of socioeconomic position included: social class, Jarman scores of patients' areas of residence, whether or not patients owned their own home, whether or not patients owned a car, whether or not they had been unemployed during the previous year and whether or not they had had further education. Social class data were only available for 84% of the 1075 respondents completing the Nottingham health profile. Those respondents for whom social class data were not available were significantly more likely to score positively on the social isolation, sleep and physical mobility dimensions of the Nottingham health profile. Not owning one's own home emerged as the measure of socioeconomic status that best predicted distress. The other measures of socioeconomic status that were significantly predictive of distress were not having had further education and having been unemployed during the last year. Different measures of socioeconomic position significantly predicted positive scores on different dimension of the Nottingham health profile. Although the Jarman score significantly predicted a positive score on the sleep dimension, it did not predict distress well when compared with the direct measures of disadvantage. There are simple, more direct measures of socioeconomic position than social class that could be collected routinely by practices which would form a better basis for the evaluation of services required to target those needs created by persisting social inequalities in health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419246 TI - Evaluation of urine sampling technique: bacterial contamination of samples from women students. AB - A urine specimen is traditionally sampled using the clean-catch midstream technique, but this technique is poorly documented. The aim of this study was to evaluate the bacterial content of urine samples taken using individual steps of the clean-catch midstream technique, or combinations of steps. One hundred and ten women students provided a total of 864 early morning urine samples, using a different sampling technique each morning. Holding the labia apart during sampling more than halved the percentage of samples containing 10(5) colony forming units per ml or more, and increased the percentage of uncontaminated samples, compared with passing urine without employing any of the precautions. Cleaning the perineum or using the midstream technique resulted in percentages no different from urination without employing any precautions. It is therefore recommended that women should be instructed to carry out the simplest effective urine sampling technique: holding the labia apart. PMID- 1419247 TI - Acute herpes zoster and postherpetic neuralgia: effects of acyclovir and outcome of treatment with amitriptyline. AB - This retrospective study was designed to assess the effects of acyclovir treatment of acute herpes zoster on subsequent postherpetic neuralgia, and to examine the effects of amitriptyline in the treatment of postherpetic neuralgia. Eighty seven patients with postherpetic neuralgia of three or more months' duration were studied: 24 of them had had their herpes zoster treated with oral acyclovir. At first presentation, only 25% of the 24 patients who had had their herpes zoster treated with acyclovir selected the word group containing burning on the McGill pain questionnaire compared with 76% of the 63 patients who had not received acyclovir. A higher proportion of patients who had had acyclovir than had not selected the word group which contains the word aching (63% versus 49%). Acyclovir thus appears to change the nature of postherpetic neuralgia. Postherpetic neuralgia was treated with amitriptyline, alone or in combination with distigmine and/or sodium valproate. There was a strong correlation between pain relief and the interval between the occurrence of herpes zoster and the initiation of treatment with amitriptyline--early treatment is almost twice as likely to be successful as late. Since conventional analgesics and sympatholytic drugs are of no benefit in the treatment of established postherpetic neuralgia, the sequelae of herpes zoster must, therefore, be recognized and treated with amitriptyline as soon as possible. PMID- 1419249 TI - Intermittent self catheterization for patients with urinary incontinence or difficulty emptying the bladder. AB - Urinary incontinence, difficulty voiding and recurrent urinary tract infections are common in general practice. In patients with multiple sclerosis, spina bifida, intervertebral disc lesions, spinal injuries or tumours, the symptoms may be associated with a high residual volume of urine owing to a neuropathic bladder. Similar complaints may occur in elderly people or in women with gynaecological problems owing to atonic urinary retention. Provided that a significant residual volume of urine is found on abdominal examination, ultrasound, x-ray or catheterization, both groups of patients may be helped by intermittent self catheterization. Intermittent self catheterization is a safe and simple technique. By catheterizing themselves between four and six times daily patients can gain control over their bladders. Abandoning indwelling catheters or bulky external appliances does much for a patient's morale and self esteem. In addition, since the bladder is being drained effectively, urinary tract infections cease to be a problem and the kidneys are safeguarded. Severe disability is not a contraindication since patients in wheelchairs have mastered the technique despite paraplegia, an anaesthetic perineum, spinal deformity, intention tremor, mental handicap, old age or blindness. Patients should be referred to urologists for a trial of intermittent self catheterization. If unsuccessful or unacceptable it can be abandoned with no long term consequences. If it is effective the benefits may be considerable. PMID- 1419250 TI - Lifestyle limitation in asthma. PMID- 1419248 TI - Determinants of outcome in smoking cessation. AB - A large amount of research has been conducted into the factors which influence outcome in attempts to stop smoking. This article reviews the literature in two main areas: first, the effects of patient characteristics on outcome, and secondly, the effectiveness of various primary care interventions. The practical implications of this research for primary care interventions to help people stop smoking are explored. PMID- 1419251 TI - GPs' recognition of need in the community. PMID- 1419252 TI - Apparent hyperglycaemia in paracetamol overdose. PMID- 1419253 TI - Health advice for travellers: the GP's role. PMID- 1419254 TI - Cholesterol screening. PMID- 1419255 TI - Treatment of non-melanoma skin cancers. PMID- 1419256 TI - Flourishing or floundering in the 1990s. PMID- 1419257 TI - Interface between primary care and specialist mental health care. PMID- 1419258 TI - Provision of, and patient satisfaction with, primary care services in a relatively affluent area and a relatively deprived area of Glasgow. AB - This paper presents the results of a survey of the structure of general practice in two contrasting areas within Greater Glasgow health board: the south west area had a more deprived social profile at the 1981 census and higher than average all cause and selected major cause standardized mortality ratios than the health board as a whole while the north west area had a more affluent social profile at the 1981 census and lower than average all cause and selected major cause standardized mortality ratios. The general practice survey data gathered in 1989 were supplemented with data from a survey of residents of the localities in three age cohorts carried out in 1987-88, which provided information on use of services, as well as perceived accessibility of and satisfaction with them. Despite the more deprived social and mortality profile of the south west area, and greater use of services, few systematic differences in the structure of general practices were found in the two areas. These findings support other studies which suggest that the stereotype of poorly resourced, low quality primary care in inner city areas may apply in London, but not elsewhere. Respondents in both areas were equally satisfied with services and found them accessible. PMID- 1419259 TI - Changes resulting from increasing appointment length: practical and theoretical issues. AB - The experience of one urban teaching practice in changing its appointment length from 7.5 to 10.0 minutes is described. Observed benefits to patients attending routine surgeries included an increased consultation time (mean 8.6 minutes before, 9.1 minutes after) and reduced waiting time (mean 19.1 minutes compared with 14.6 minutes). Overall, workload was unchanged but improving the 'fit' between supply and demand was associated with loss of flexibility--a greater number of extra patients required to be seen, apparently because fewer appointments were available at the start of each day. Waiting and consultation times in teaching surgeries and trainee surgeries (booked throughout at 10.0 minute intervals) were unchanged in response to the new arrangements. The changes introduced were well received by medical and reception staff although their response was not formally measured. Planning the organization of an appointment system requires several distinct decisions to be made. The preferred or actual average length of consultations has to be decided and booking arrangements designed to enable this to take place without the doctors persistently running over time. The number of appointments per week required to meet anticipated demand has to be calculated on the basis of list size and expected annual consultation rate. However, an exact fit between supply and demand will lead to congestion of the system and it appears that flexibility in the form of an overprovision of appointments to projected demand of about 120% should be built in. Sufficient vacant slots must be provided at the start of each day to allow sufficient flexibility to avoid excessive numbers of patients having to be accommodated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419260 TI - General practice based diabetes surveillance: the views of patients. AB - Forty three patients with non-insulin dependent diabetes registered at two suburban practices were interviewed at least one year after the introduction of an organized general practice based system of diabetic surveillance and the results compared with data gathered from interviews administered before the introduction of the system. Structured data from the two interviews were compared in relation to the importance which patients attached to diabetes and its medical review, patients' preference for place of future review and the health professionals from whom they wished to receive diabetes care. Patients' ratings of the performance of health professionals on various aspects of care were compared with the ratings given before the introduction of the new service. At the follow-up interviews the reasons behind patients' responses to the structured questions were explored using a qualitative method. The introduction of a general practice based diabetes service was marked by an improvement in attendance for diabetes monitoring (56% before introduction, 98% in the year following introduction). This was associated with an increase in the importance which patients attached to diabetes and its medical review. After experience of diabetes care in general practice, patients remained enthusiastic about general practice involvement and confident in their general practitioners' knowledge about diabetes management. In spite of an improvement in the patients' ratings of hospital doctors' communication skills, they continued to rate general practitioners significantly more highly in these skills (P < 0.01) and in terms of convenience and accessibility (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419261 TI - How many people think they have hay fever, and what they do about it. AB - Little is known about the number of people who perceive themselves to be sufferers of hay fever. This study investigated how many people between the ages of 15 and 59 years perceived themselves to be hay fever sufferers and how they treated themselves. The study was carried out in a general practice in Arnold, Nottingham, using a postal questionnaire, to which the response rate was 77% from a sample size of 1062. Of the 813 respondents, 232 (29%) claimed to have had hay fever within the last two years. The prevalence of hay fever decreased significantly with age, and was associated with a history of asthma. One hundred and twenty five sufferers (54%) used over the counter treatments for their hay fever, and one third of these said that they felt drowsy after using them. These findings point to the need for general practitioners to be aware that a number of people, more than has been indicated by previous surveys, perceive themselves to be hay fever sufferers and are prepared to treat themselves using over the counter preparations. PMID- 1419263 TI - General practitioners' attendance at courses accredited for the postgraduate education allowance. AB - An analysis was undertaken in the northern half of the South Western Regional Health Authority of general practitioners' attendance at courses accredited for the postgraduate educational allowance over one year. A total of 358 courses provided 2341 hours of accredited education and produced a total general practitioner attendance of 50,389 hours. The mean attendance per principal in the area was 49.2 hours although the region may be a net importer of attenders from outside the area. Of the 50,389 total hours of attendance, 28.3% were in health promotion, 48.2% in disease management and 23.5% in service management. Course provision and attendance varied considerably over the year. September, October and November accounted for 42.7% of the total hours of attendance, compared with 6.8% in June, July and August. Courses of two to four days or of one week duration accounted for 48.3% of total attendance hours; 10.1% of total attendance hours were at commercially organized courses and 5.6% at courses organized by practices. A total of 66.1% of attendance hours were in postgraduate centres and 6.8% in the practice. Courses with more than 30 participants accounted for 15.9% of courses attended. A total of 174 general practitioners and others organized courses, 21 of them influencing 33,521 hours of general practitioner education. The study shows that in this area, there was an encouraging provision, range and uptake of continuing education courses for general practitioners. The concentration of educational activities in postgraduate centres underlines the need for increased provision for developing educational skills for clinical tutors. PMID- 1419262 TI - Prevalence of heart failure in three general practices in north west London. AB - There is little recent information on the prevalence of heart failure in the United Kingdom. Assuming that patients with heart failure would be taking diuretic drugs all such patients were identified in three general practices in north west London. The practice records of these patients were examined to determine which patients had heart failure. Of the 30,204 patients served by the practices, 117 had heart failure, a prevalence of 3.9 per 1000 patients. The mean age of these patients was 74 years. The prevalence of heart failure among patients under 65 years of age was 0.6 per 1000 patients rising to 27.7 per 1000 among those aged 65 years and over. The aetiology of heart failure was considered to be coronary heart disease for 32% of patients, valve disease for 19%, hypertension for 6%, cor pulmonale for 4% and congenital heart disease for 2%. The aetiology for the remaining 37% of patients was unknown. Most patients were referred to hospital and only 20% had been treated solely by the general practitioner. An electrocardiogram and chest radiograph had been obtained for over 80% of patients but only 28% had an echocardiogram. Heart failure occurs primarily in elderly patients, and coronary heart disease is the dominant aetiological factor. PMID- 1419265 TI - Forty years on--and back. PMID- 1419264 TI - New strategies for higher professional education. AB - Since the original recommendation in 1968 for a period of higher professional education, the development of this form of education has been slow. However, in 1990 a working party was established by the education division of the Royal College of General Practitioners to report on higher professional education. This paper describes some of the early work of the working party and its recommendations with particular emphasis on educational strategies, assessment and accreditation. A flexible, learner centred approach needs to be developed to encourage autonomy. Educational strategies are described which value previous experience and allow for a shift of responsibility for learning from the teacher to the learner. PMID- 1419266 TI - Skin lesion excision in general practice. PMID- 1419267 TI - Use of accident and emergency services. PMID- 1419268 TI - Prophylaxis against malaria. PMID- 1419269 TI - GP's attitudes towards drug users. PMID- 1419270 TI - Cost effectiveness of minor surgery in general practice. PMID- 1419271 TI - Coronary heart disease. PMID- 1419272 TI - Screening for diabetes--an alternative view. PMID- 1419273 TI - Calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the tracheal epithelium of rats: an immunohistochemical study by means of whole mount preparations. AB - The airway mucosa is known to be densely supplied with several types of peptidergic nerve fibers. The distribution of the nerve fibers in a large extent of the mucosa, however, has been difficult to visualize by observation of conventional thin sections. In the present study, whole mount preparations of the rat tracheal mucosa were designed to demonstrate calcitonin gene-related peptide (CGRP)-containing nerves which are most predominant among peptidergic nerves in the trachea. The mucosal sheet of the trachea was separated from the cartilaginous base by means of dispase, a protease, to be processed to immunohistochemistry for CGRP. In the cartilaginous portion, thick nerve bundles immunoreactive for CGRP ran transversely between the cartilage rings, sending terminal branches toward the epithelium. In the membranous portion, immunoreactive nerve bundles were thinner than those in the cartilaginous portion and ran longitudinally. A very dense nerve plexus of CGRP-immunoreactive fibers was demonstrated to extend in the basal part of the epithelium; every epithelial cell appeared to contact more than one nerve fiber. Immunohistochemistry of the whole mount preparations also clearly demonstrated the distribution and entire shape of broncho-pulmonary paraneurons scattered in the epithelium. Ultrastructurally, the CGRP-immunoreactive intraepithelial nerves were found to lack myelin and Schwann sheaths, and to run through the bases of the epithelial cells; they were most frequently surrounded by the cytoplasmic processes of the epithelial cells. The present study demonstrates that immunohistochemistry of whole mount preparations is a useful tool to morphologically analyze neuronal and paraneuronal distribution throughout the tracheal epithelium. PMID- 1419275 TI - The topographic organization of the retinal ganglion cell layer of the lizard Ctenophorus nuchalis. AB - The numbers of neurons of the ganglion cell layer (GCL) and their distribution in the retina of an Australian lizard Ctenophorus nuchalis were investigated. Retinal wholemounts and sections were prepared for light microscopic and optic nerves for electron microscopic study. Counts of cell numbers in the GCL from wholemounts varied from 200,000 to 380,000. Neurons in the GCL were non-uniformly distributed, forming a high cell density streak along the naso-temporal axis of the retina. Neurons of the GCL formed 2 to 9 layers in the visual streak and a single layer in the rest of the retina. The number of neurons of the GCL in this area was estimated at about 2,100,000. Although the visual streak represented only 16% of the total retinal surface area, it contained about 90% of all neurons of the GCL. Optic axon counts yielded 147,000 myelinated and 2,643,000 unmyelinated fibres. The estimated optic fibre number of 2,790,000 was 18.2% less than the total number of neurons counted from sections in the GCL of the same eye. The unexpected high number of neurons in the area of the visual streak indicates that cell numbers obtained only from wholemount preparations may vastly underestimate the total neuron numbers in the GCL of the lizard retina. PMID- 1419274 TI - The dependency of collagen fibrillogenesis in vitro on fibroblast culture conditions. Fibroblasts in mono- and multi-layers. AB - The extracellular matrix produced by monolayer and tridimensional cultures of fibroblasts was investigated using histochemical and ultrastructural methods. In monolayer cultures, collagen and proteoglycans produced by fibroblasts could not be organized into morphologically recognizable structures. Tridimensional fibroblast cultures produced a well organized matrix with periodic, parallel ordered collagen fibrils of 50 nm diameter, criss-crossed by alcianophylic segments 6-10 nm thick in diameter and 100-300 nm in length, parallel to each other, perpendicular to the collagen fibrils and spaced 67 nm from each other. Some alcianophylic segments lay perpendicular to the above described ones, with maximum lengths of 65-70 nm. Alcianophylic segments are the ultrastructural evidence of structural proteoglycans. These observations suggest that the culture conditions influence the collagen and proteoglycans secretion, so that the final organization of the matrix results quite different. PMID- 1419276 TI - Morphological modifications during long-term survival of Meckel's cartilage hypertrophic chondrocytes transplanted in the mouse spleen. AB - To examine the ultimate fate of hypertrophic chondrocytes, Meckel's cartilage bars from 18-day-old mouse embryos were transplanted into isogenic mouse spleen for 3, 7, 14 and 21 days and observed at the light and electron microscopic levels. The midportions of these Meckel's cartilage bars were used as explants; they were characterized by many hypertrophic chondrocytes containing euchromatic round nuclei, a large amount of glycogen particles, and some vacuoles. Grafted cartilage adapted well to the splenic tissue, showing intense metachromasia around the territorial matrix. Ultrastructural observations indicated that the number of large vacuoles and glycogen aggregates in the hypertrophic cells became markedly reduced with grafting time, whereas the Golgi apparatus and rough endoplasmic reticulum were well-developed. Needle-like crystals showing initial apatite deposition appeared in association with matrix vesicles; these proliferated as time elapsed after transplantation. On day 14 after transplantation, cells displaying such various structural features as pyknotic nuclei, large vacuoles, and cytoplasmic shrinkage were noted in addition to intact hypertrophic chondrocytes. Following resorption of the calcified cartilage by multinucleated giant cells, many osteoblasts appeared along the border of the calcified matrix. Some remaining hypertrophic cells in the calcified matrix had transformed into osteocyte-like cells. On day 21, the resorbed area of the calcified cartilage was invaded by many blood vessels. Hypertrophic chondrocytes, now exposed from cellular lacunae, and the osteocyte-like cells in the calcified matrix displayed involutional changes. The present study showed that, although the hypertrophic chondrocytes in Meckel's cartilage essentially underwent regressive changes, they retained the ability to stimulate endochondral ossification within the microenvironment of the spleen. In addition, some of these cells were transformed into osteocyte-like cells. PMID- 1419277 TI - Odontoclastic resorption at the pulpal surface of coronal dentin prior to the shedding of human deciduous teeth. AB - Histological and histochemical observations of more than 150 extracted human deciduous teeth revealed that, prior to shedding, odontoclastic resorption as a rule takes place at the pulpal surface of coronal dentin. We also found that this phenomenon occurs in all kinds of deciduous teeth. The process of this internal resorption of coronal dentin of deciduous teeth clearly showed time-related histological changes. During the time the roots were actively being resorbed, the pulpal tissue retained its normal structure. However, when root resorption neared completion, inflammatory cells started to gradually infiltrate into the pulp, and odontoblasts began to degenerate. After that, multinucleate odontoclasts appeared, and resorption proceeded from the predentin to the dentin. The odontoclastic activity was initially detected only on the pulpal surface at the bottom areas of the crown. It gradually spread towards the pulpal horn regions along the wall of the pulp chamber. However, this internal resorption of coronal dentin did not continue until the teeth were finally shed. After the elimination of resorption, the resorbed dentin surface was repaired by a cementum-like deposition or covered with fibrous connective tissue. PMID- 1419278 TI - Plasma cells in the spleen of the Aleutian skate, Bathyraja aleutica. AB - Splenic white pulp of the Aleutian skate (Bathyraja aleutica), an elasmobranch, was investigated using light and transmission electron microscopy. The major cellular constituent was plasma cells, of the typical Marshalko type, characterized by well developed rough-endoplasmic reticulum and a Golgi complex. The morphology of the rough-endoplasmic reticulum was variable, being lamellar in some cells and spherical in others. Plasma cells with distended cisternae of rough-endoplasmic reticulum and cells with Russel bodies were often observed. Only a small number of lymphocytes were encountered. These findings indicate that the splenic white pulp is the major site for immunoglobulin production in this fish, thus confirming our previous immunocytochemical observation. Globules presumably containing immunoglobulin were found consistently associated with the Golgi complex. The secretion mechanism of immunoglobulin by plasma cells is discussed in connection with the globules. PMID- 1419279 TI - Fine structure of the dorsal epithelium of the tongue of the Japanese terrapin, Clemmys japonica (Cheloia, Emydinae). AB - As reptiles are situated phylogenetically between the amphibians and the mammals, they exhibit considerable variation in the structure of their tongues. The present study, one of a series of studies on reptile tongues, aims to demonstrate the three-dimensional structure of the dorsal lingual surface of a turtle, the Japanese terrapin Clemmys japonica, and to clarify the ultrastructural features of the lingual epithelial cells. In the study lingual papillae were observed by scanning electron microscopy to be widely distributed over the dorsal surface of the tongue. Irregularly shaped (conical, columnar or angular) papillae were located in the anterior and central areas, and ridge-like ones, in the latero posterior area. Histological examination revealed that the connective tissue penetrated into the core of the papillae, and the epithelium was of a stratified squamous and/or cuboidal type. Under the transmission electron microscope, two types of cells were identified in the intermediate layer of the apical epithelium of the lingual papilla: one type was probably an immature mucous cell, whereas the other was elongated in a baso-apical direction, its cytoplasm containing fine granules. In the surface layer of the apical epithelium, typical mucous cells and cells containing numerous, fine, electron-lucent granules were recognized. Both types of cells possessed microvilli on their free-surfaces. In the lateral epithelium of the lingual papillae, the cytological features from the basal layer to the superficial intermediate layer were essentially the same as in the apical epithelium. However, in the surface layer, mucous cells were significantly larger in number than in the apical epithelium. PMID- 1419280 TI - Reticular endings of Purkinje cell axons in the rat cerebellar nuclei: scanning electron microscopic observation of the pericellular plexus of Cajal. AB - The pericellular plexus of Purkinje cell axons in the cerebellar nuclei was first recorded by Cajal (1911), using the Golgi method. The present study observed the axonal plexus in the rat by scanning electron microscopy after the plexus' detachment from the soma of target neurons by NaOH maceration. The pericellular plexus revealed numerous axons with ellipsoidal and moniliform swellings. They branched and crossed with each other to form, as a whole, a reticulum which enveloped the target neuron instead of multiple isolated boutons. Some axon terminals were separated from each other by thin glial processes, while others lacked such septa, thus being directly juxtaposed. Immunohistochemistry for spot 35 protein, a Purkinje cell-specific protein, detected similar beaded and reticular axons terminating on the neuronal somata, confirming their identification as Purkinje cells. Transmission electron microscopic observation showed that most of the axon terminals in question contained elliptical vesicles, characteristic for Purkinje cells. The vesicles were not accumulated toward small patchy areas of synaptic specialization but disseminated along the entire length of the terminal portion of axons. PMID- 1419281 TI - Microstructures of the osseous spiral laminae in the bat cochlea: a scanning electron microscopic study. AB - The architecture and surface structures of the primary and secondary osseous spiral laminae in the cochlea of the bat, an animal able to hear high frequency sounds, were examined by scanning electron microscopy to understand the micromechanical adaptations of the bony supportive elements in the inner ear to the specific hearing function. The bat used was Myotis frater kaguyae. The myotis bat cochlea was seen to consist of a hook and a spiral portion with one and three quarter turns and was characterized by: 1) a distinct ridge-like projection running spirally along the middle line on the vestibular leaf of the primary osseous spiral lamina; 2) a wide secondary osseous spiral lamina; and 3) a narrow spiral fissure between the primary and secondary osseous spiral laminae. The ridge on the primary osseous spiral lamina was 150 microns high in the hook and basal turn, then lowered toward apex, and flattened before the apical end. The surface structures appeared to provide a firm anchorage of the auditory teeth. The secondary osseous spiral lamina, which anchors the fibers of the basilar membrane, was sharply projected and measured 150 microns in width in the hook, and then narrowed gradually toward apex to disappear in the helicotrema. The spiral fissure for the basilar membrane was about 40 microns in width in the hook and about 120 microns in the apical turn. The findings suggest the presence of a narrow and rigid basilar membrane with a high amount of fibers and a strong bony support to the auditory teeth for scaffolding the tectorial membrane during intense vibration in response to high frequency sounds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419282 TI - A European initiative for prostatic cancer. PMID- 1419283 TI - Immune ageing and cancer. PMID- 1419284 TI - The darkest ages of tobacco. PMID- 1419286 TI - Variations in breast cancer management between a teaching and a non-teaching district. AB - We compared the management and outcome of 999 women with breast cancer presenting between 1982 and 1986 at two centres in a region, one in a teaching district. A comparison was also made with relevant research and The Kings Fund Consensus Statement. The centres frequently differed markedly in the investigations done, diagnostic procedures, histology reporting, axillary sampling, and in the treatment given, also differing from the Consensus with no trend towards it. Survival was better at the teaching centre, both disease-free (N.S.) and overall [odds ratio 1.46 (1.16-1.84) P = 0.0009 unadjusted]. This should be interpreted cautiously as the median follow-up time was relatively short and the study was non-randomised. We conclude that how women with breast cancer are managed is determined as much by where they are referred as by scientific evidence. This indicates the need to introduce standards and protocols into business plans, making audit and service specifications easier. PMID- 1419285 TI - 4-hydroxyandrostenedione: a new treatment for postmenopausal patients with breast cancer. AB - We have evaluated 4-hydroxyandrostenedione, a specific inhibitor of aromatase, as treatment for breast cancer in a phase I dose-ranging study and a phase II study of the best-tolerated dose. 168 postmenopausal patients with locally advanced and metastatic breast cancer were treated intramuscularly. 19% of patients attained a complete or partial response but 26% of those who completed at least 4 weeks treatment responded. Side-effects were least in the group receiving 250 mg every 2 weeks. 13% of patients experienced local discomfort due to the injection and 5% had other side-effects. Serum oestradiol fell to 42.4 and 26.5% of baseline at 7 days after the start of treatment with the 250 mg and 500 mg dose, respectively. We conclude that 4-hydroxyandrostenedione at 250 mg every 2 weeks is a safe and effective form of treatment for postmenopausal patients with metastatic breast cancer. PMID- 1419287 TI - Serum vanillylmandelic acid/homovanillic acid contributes to prognosis estimation in patients with localised but not with metastatic neuroblastoma. AB - In 211 patients with neuroblastoma, serum vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were determined and correlated to stage, histological differentiation, ferritin, neuron-specific enolase, lactate dehydrogenase (LDH) and outcome. Elevated serum VMA and/or HVA levels were found 16% less frequently than elevated urine levels. The incidence of the elevated serum levels increased with stage (stages I-III 58%, IV 78%, IVS 100%). Increased VMA/HVA ratios were not associated with a higher grade of tumour differentiation. Serum ferritin and neuron-specific enolase showed no correlation, and LDH a borderline non-random correlation with the serum catecholamine metabolites. Using age-related reference values a quotient of serum VMA/HVA (P = 0.061) < 0.7 indicated a poorer event-free survival (48 +/- 10%) than ratios > or = 0.7 (event free survival 81 +/- 6%) for children with localised neuroblastoma (P = 0.0004). No correlation with prognosis was detected for patients with stage IV and stage IVS disease. We conclude that serum VMA and HVA determinations may be useful as tumour markers for 71% of neuroblastoma patients, and aid in estimating the prognosis in children with localised disease. PMID- 1419288 TI - Treatment of poor prognosis Burkitt's lymphoma in adults with the Societe Francaise d'Oncologie Pediatrique LMB Protocol--a study of the Federation Nationale des Centres de Lutte Contre le Cancer (FNLCC). AB - 14 adult patients between 16 and 50 years old with small non-cleaved cell lymphoma (Burkitt's lymphoma) were prospectively treated from 1982 to 1990 with the LMB protocols of the Societe Francaise d'Oncologie Pediatrique (SFOP). No HIV positive patients were included. All patients had extensive disease with bad prognosis factors, i.e. 10 patients had Murphy stage III and 4 had stage IV with bone marrow involvement. The LMB protocols were characterised by high-dose fractionated cyclophosphamide, high-dose methotrexate (HD-MTX), and cytosine arabinoside. No local or central nervous system irradiation was used. Treatment duration ranged from 5 (LMB 84) to 12 (LMB 81) months. There were no therapy related deaths. All patients achieved complete remission (CR). 6 patients relapsed between 2 and 30 months following CR. 8 of the 14 patients (57%) are still alive and disease-free after treatment by LMB protocol alone. 2 patients were salvaged with bone marrow transplantation after relapse and a total of 10 out of 14 patients (71%) are disease-free at the time of this report. Our results showed the high curability of advanced Burkitt's lymphoma using a paediatric protocol, even in adult patients. The LMB protocol may be applied to adult patients but requires intensive care during the induction period. PMID- 1419289 TI - Phase II study of tauromustine in malignant glioma. AB - 46 eligible patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) and clinical and computed-tomography-confirmed relapse following primary surgery and radiotherapy received oral tauromustine 130 mg/m2 every 5 weeks. A prospective design allowed for concurrent assessment of both clinical and radiological responses and drug toxicity. 41% of patients improved clinically whilst 46% improved radiologically with 3 complete, 7 partial and 7 minimal responses (WHO criteria). Toxicity included grade III or IV gastrointestinal side effects (15%), grade III or IV leukopenia (24%) and grade III and IV thrombocytopenia (44%). In 9 clinically responding patients, haematological toxicity led to discontinuation of treatment. All patients were followed-up until death and second-line chemotherapy was not used. Median post-treatment survival was 26 weeks for patients with GBM and 57 weeks for patients with AA. Overall 2 year survival rate was 69% for AA and 23% for GBM. Tauromustine given at the time of relapse has demonstrable antitumour activity in patients not previously treated with chemotherapy. PMID- 1419290 TI - Mitozantrone and methotrexate chemotherapy with and without mitomycin C in the treatment of advanced breast cancer: a randomised clinical trial. AB - Patients with advanced breast cancer were randomised to 3M (mitozantrone 6.5 mg/m2q 21 days, methotrexate 30 mg/m2q 21 days, mitomycin C 6.5 mg/m2q 42 days) or 2M (as 3M but without mitomycin C). The objective response rates of 30% in 51 evaluable patients receiving 3M and 26% of 54 patients receiving 2M were not significantly different. 4/16 patients not responding to 2M responded to 3M on crossover. Both regimes were well tolerated but there was significantly less haematological toxicity and fewer dose reductions and delays with 2M. We conclude that patients should initially be treated with 2M and that non-responding patients should be crossed to 3M. PMID- 1419291 TI - A phase II study of 5-fluorouracil and high-dose folinic acid in combination with cyclophosphamide and mitoxantrone for advanced breast cancer. AB - 38 patients with advanced breast adenocarcinoma were treated in a phase II study with 5-fluorouracil and high-dose folinic acid combined with cyclophosphamide and mitoxantrone. 6 patients had received prior chemotherapy for advanced disease, all with an anthracycline-containing regimen. Treatment was generally well tolerated. The most common side-effect was myelosuppression, with 1 toxic death due to leukopenia-related sepsis. 1 patient developed severe congestive heart failure 12 months from the end of therapy. 36 patients were evaluable for response. The overall response rate was 55%. Median duration of response was 8 months and median survival time was 16 months. This regimen warrants further investigations. PMID- 1419292 TI - Borderline malignancy of the ovary and controlled hyperstimulation, a report of 2 cases. AB - We report 2 patients who developed a borderline malignancy of the ovary after treatment with follicular stimulants in the context of an in vitro fertilisation (IVF) programme. In both cases, conservative surgery for the borderline malignancy was sufficient treatment. Ultimately, both patients became pregnant, 1 after IVF treatment and 1 without treatment, and both delivered healthy babies. In addition to the presentation of both cases, the literature concerning the possible risks of treating patients with high dosage, exogenously administered hormones is reviewed and the possible association between exogenous hormones and the risk of developing ovarian cancer is discussed. PMID- 1419293 TI - Unexpected prolonged myelosuppression after mitomycin, mitoxantrone and methotrexate. AB - 28 patients (26 with breast cancer and 2 with colon cancer) received mitomycin, mitoxantrone and methotrexate (MMM). Half the patients had grade III-IV leukopenia and 29% had grade III-IV thrombocytopenia. The median time of recovery to WHO grade 0 was 62 and 128 days, respectively. Thrombocytopenia and leukopenia were more frequent and longer lasting after the three-drug part of the therapy, which suggests a critical role for mitomycin in this toxicity. PMID- 1419295 TI - Tumour burden as the main indicator of prognosis in Hodgkin's disease. AB - A method of estimating the total tumour burden in patients with Hodgkin's disease was devised, combining the number of involved regions with the tumour size in each region. Further, a method of estimating the total tumour cell burden was devised, combining the estimate of the total macroscopic tumour burden with an estimate of the concentration of tumour cells in the tumour tissue. The prognostic significance of the total tumour burden was examined in multivariate studies of 300 patients in pathological stages I and II treated in the Danish National Hodgkin Study and 506 patients in all stages treated at the Finsen Institute, Copenhagen, Denmark, during a 15-year period. The total tumour burden turned out to be the most important prognostic factor in Hodgkin's disease. Most of the hitherto known prognostic factors were shown to be correlated with the total tumour burden and to lack independent prognostic significance. PMID- 1419294 TI - Uroepithelial and nephrotubular toxicity in patients receiving ifosfamide/mesna: measurement of urinary N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin. AB - The effect of three ifosfamide/mesna regimens on urinary N-acetyl-beta-D glucosaminidase (NAG) activity and beta-2-microglobulin (beta 2 M) was studied. All regimens produced significant increases in these urinary proteins, indicating nephrotubular damage. In regimen A (n = 15), plasma nitrobenzylpyridine (NBP) alkylating activity area under the curve (AUC) on day 1 correlated with the percentage increase above baseline of maximum urinary NAG activity (r2 = 0.538, P = 0.0022) and maximum beta 2 M concentration (r2 = 0.413, P = 0.0097). In regimen B (n = 5), plasma NBP alkylating activity AUC correlated with the percentage increase above baseline of maximum NAG activity (r2 = 0.843, P = 0.03) and beta 2 M (r2 = 0.78, P = 0.046). In these two regimens the renal exposure to ifosfamide metabolites correlated with the increases in urinary NAG and beta 2 M. The relation of these urinary protein abnormalities to longer term effects on renal function with different ifosfamide/mesna schedules requires further study. PMID- 1419296 TI - Evaluation of a breast cancer screening programme--the DOM project. AB - In several studies it has been shown that breast cancer screening by means of mammography reduces breast cancer mortality. To ensure that when organising a service screening programme the aim is reached, it is necessary to control and monitor the process. This is possible by several methods. In this study, disease free intervals and survival rates were used as monitoring tools. The DOM project, a breast cancer screening programme for women aged 50-64 years old at intake, started at the end of 1974. All breast cancer cases diagnosed between 1973 and 1989 were followed up to 1991. It is clear that disease-free interval and survival rates are proper predictors of the effects of screening on breast cancer mortality. PMID- 1419297 TI - Constitutive tissue factor expression of human breast cancer cell line MCF-7 is modulated by growth factors. AB - Expression of tissue factor, the initiator of the extrinsic coagulation protease cascade, is a feature of certain malignant tumours. To study the modulation of tissue factor expression we incubated the breast cancer cell line MCF-7 with several growth factors. Epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha) and interleukin-1 (IL-1) rapidly increased tissue factor expression of MCF-7 cells peaking at 6-8 h after starting point of incubation, as determined by clotting test, enzyme linked immunosorbent assay and flow cytometry. The data presented support the hypothesis that modulation of constitutive tissue factor expression in tumour cells by TGF alpha and IL-1 could also occur in vivo possibly resulting from interactions of stromal and cancer cells. The meaning for tumour biology, however, remains unclear. PMID- 1419298 TI - Modulation of tumour marker CA-125 expression in cultured ovarian carcinoma cells. AB - The aim of this study was to elucidate whether proliferation of ovarian carcinoma cells may affect the biosynthesis and release of CA-125. In a cell culture model the tumour marker CA-125 expression in cytosol, surface membrane, and release into culture medium was studied in six human carcinoma cell lines. Cell cycle analysis of propidium iodide stained nuclei was performed using a fluorescent activated cell sorter. The turnover of CA-125 is very rapid, within 24 h the equivalent amount found in each cell was also released in the supernatant culture medium. A good relation between cytosolic, membrane, and released CA-125 was observed. CA-125 expression was associated predominantly with the G0/G1 phase of the cell cycle and was dependent on cell density. The results presented here demonstrate that factors associated with tumour cell proliferation could influence the CA-125 serum level in ovarian cancer patients. PMID- 1419299 TI - Biological characterisation of primary and metachronous lesions in breast cancer patients. AB - Proliferative activity, evaluated as [3H]thymidine labelling index ([3H]dT LI), and hormone receptors were determined on 97 primary breast cancers and on metachronous lesions from the same patient. Overall, the [3H]dT LI of metachronous lesions was significantly higher than that of the primary tumour (P = 0.003). Hormone receptor profiles of the two lesions were similar in about 75% of the cases; disagreements were mainly due to a disappearance of hormone receptors in metachronous lesions. In contralateral tumours, [3H]dT LI and hormone receptors were unrelated to those of the relative primary lesion. In this series of relapsing patients, [3H]dT LI was unrelated to hormone receptor status in the primary tumour, but it was higher in the metachronous lesions from patients with hormone receptor-negative primary tumours. For patients given no systemic therapy between surgery and relapse, the time to develop local-regional recurrences or contralateral tumours was inversely related to the [3H]dT LI of the metachronous lesions. PMID- 1419300 TI - The effect of a low-fat diet on hormone levels in healthy pre- and postmenopausal women: relevance for breast cancer. AB - It has been postulated that differences in the levels of circulating hormones may be the explanation for the epidemiological link between per capita dietary fat intake and the incidence of breast cancer. We have investigated this possible relationship in 19 postmenopausal, and 18 premenopausal women who completed a 4 week period on a diet aiming to reduce fat intake to around 20% of total kilocalories. 7-day dietary records revealed a significant decrease in dietary fat intake in both the pre- and postmenopausal groups (from 37.2% of calories from fat to 23.2% and from 37.9 to 24.3%, respectively). There was a minor increase in the level of sex hormone-binding globulin, and a small decrease in prolactin in the postmenopausal group, which were of borderline significance. There were no significant changes in total oestradiol (E2), or non-protein-bound (free) E2 concentrations. In the premenopausal group there were no significant changes in any of the hormone levels investigated. PMID- 1419301 TI - Patterns of childhood cancer incidence and mortality in Europe. AB - Histograms including age-standardised (0-14 years, world standard) incidence and mortality rates from selected childhood cancers are presented for 21 European cancer registration areas and 24 countries. The overall range of variation in all childhood cancer incidence rates across various cancer registration areas in Europe was around a factor 1.5, with highest rates in Spain, Italy, Sweden and France, and lowest rates in Poland, Hungary, UK, Germany and Yugoslavia. For most single cancer sites, however, the observed pattern is essentially attributable to random variation alone. A clearer pattern, however, emerged with reference to mortality. The overall range of variation, in fact, was around a factor two in both sexes, with highest rates in Bulgaria, Portugal, Hungary, Czechoslovakia and Poland, and the lowest rates in Austria, UK, Germany, The Netherlands and Finland. Trends in mortality from childhood cancers between 1950 and 1989 were also presented. Recent declines were observed for total childhood cancer mortality, leukaemias, kidney cancer (Wilms' tumours), Hodgkin's disease and other lymphomas in most European countries. These declines, however, were generally earlier and larger in northern as compared with southern and, mostly, with eastern European countries. This pattern of trends likely reflects the different adoption and impact of newer efficacious therapies of childhood cancer, and hence, confirms that there is ample scope for further reduction in childhood cancer mortality in several eastern and some southern European countries. PMID- 1419302 TI - Risk factors for kidney cancer in New South Wales--I. Cigarette smoking. AB - In a population-based case-control study of kidney cancer in New South Wales, data from structured interviews with 489 cases of renal cell cancer (RCC), 147 cases of renal pelvic cancer (CaRP) diagnosed in 1989 and 1990, and 523 controls from the electoral rolls confirmed an increased risk associated with cigarette smoking in both types of cancer. The risk among current smokers was consistently higher than among ex-smokers, and was nearly twice as great for CaRP than for RCC. Additional information provided by this study includes reduced risks following cessation of smoking within 12 years for CaRP, but only after 25 years for RCC. Starting to smoke before, rather than after, the age of 18 years is linked independently with almost twice the risk for CaRP, but does not affect the risk for RCC. No independent trend was found with number of cigarettes smoked per day. PMID- 1419303 TI - The role of local treatment in the cure of cancer. PMID- 1419304 TI - Graft vs. leukaemia reactions in chronic myeloid leukaemia. AB - A 39-year-old female relapsed 36 months after allogeneic bone marrow transplantation for chronic myeloid leukaemia. Infusion of peripheral blood leucocytes from her bone marrow donor resulted in complete remission, and she remains leukaemia-free 18 months later. This case provides direct evidence for a 'graft vs. leukaemia' (GVL) effect contributing to the eradication of leukaemia after marrow transplantation. Existing evidence for GVL and its possible mechanisms are reviewed. PMID- 1419305 TI - Classification of Hodgkin's disease: yesterday, today and tomorrow. PMID- 1419306 TI - Adjuvant tamoxifen in postmenopausal patients with breast cancer and negative axillary lymph nodes. PMID- 1419307 TI - Overcoming tumour radiation resistance resulting from acute hypoxia. PMID- 1419308 TI - Overcoming tumour radiation resistance resulting from acute hypoxia. PMID- 1419309 TI - Interleukin-2 therapy for metastatic uveal melanoma. PMID- 1419310 TI - [Primary gastric lymphomas]. AB - A series of 13 patients with primary gastric lymphoma treated between 1981 and 1990 are presented. Primary gastric lymphoma made up 4.8% of all gastric tumors treated during this period of time. Histologically, there were 3 lymphoplasmocytoid and 3 centroblastic forms (according to Kiel's classification) followed by 2 lymphocytic and 2 centrocytic-centroblastic. According to Mushoff's classification. 4 patients belonged to stage I E, 3 to II E1, 3 to II E2, 2 to III E, and one patient to stage IV E. In all cases gastrectomy was performed (9 subtotal and 4 total) although 3 out the former were palliative (23%). The operative morbidity was 30.7% and the mortality 7.7%. Seven patients received additional treatment with chemotherapy. Survival after 2 years was 70%. PMID- 1419311 TI - [The recurrence of colorectal cancer and blood transfusion]. AB - Report of a retrospective study on 303 patients operated from colorectal carcinoma to whom colonic resection was done in B and C stages of Astler-Coller's classification. The aim was to try to find a relation between blood transfusion and colorectal carcinoma recurrence. The statistical study is made with the program LOGIT, studying the surgical incision, evolutive stage and blood transfusion variables. The significant contribution of each variable in the occurrence of recurrence is studied with the Wald Test. As a result it can be deduced that the prognosis of colorectal cancer is influenced by three factors: the evolutive stage, the surgical incision (1.87 times more frequent for the abdomino-perineal) and the transfusion of more of three units of blood in the perioperative period which multiplies by 2.85 the risk of recurrence of colorectal carcinoma. In our hospital almost exclusively red cell concentrates (including red cells, white cells and minimal fraction of plasma), are transfused; possibly the white cells are responsible for the recurrence. PMID- 1419312 TI - [The prognosis of colorectal cancer with synchronous liver metastases]. AB - Between January 1985 and December 1989, 583 patients with carcinoma of the colon and rectum have been studied. In 85 with synchronous liver metastases discovered at laparotomy and followed-up, median survival time has been 5.8 months and 1 and 3 year survival 23 and 6 percent respectively. Favorable factors for survival were rectosigmoid location, single metastasis in the right hepatic lobe, normal values of alkaline phosphatase, resection of the tumor as well as stage II of Duke's classification. PMID- 1419313 TI - [A biliary fistula after T-tube removal in the transplant patient: its diagnosis by Tc-99m-HIDA]. AB - The Tc-99m HIDA scan is a valuable study after liver transplantation, associated with other image techniques. We have used this technique as a reliable and objective diagnostic method for biliary fistula after removal of the T-tube in 5 liver transplantation patients with pain after T-tube removal. All five patients who developed fistula not only were diagnosed immediately but, furthermore, the surgical technique was indicated by the gammagraphic study. After this experience, we propose to remove the T-tube during the Tc-99 HIDA scan. PMID- 1419314 TI - [Primary gallbladder carcinoma. A review of 41 cases]. AB - We present a retrospective study of primary carcinoma of the gallbladder with a total of 41 cases over a period of 11 years. In the majority of cases the clinical presentation (cholelithiasis, choledocholithiasis); there were only 7 cases of suspected diagnosis, mainly through the use of new diagnostic techniques (echography, computerized tomography). The classification used is that described by Nevin (1976) of affection of gallbladder wall and adjacent tissues. The conclusions of our study are as follows: a) primary neoplasias of the gallbladder are aggressive tumours carrying a poor prognosis aggravated usually late diagnosis due to the scarce symptomatology, b) given the high incidence of cholelithiasis, it is advisable to perform routine cholecystectomy, c) survival is related to the histological grading of the tissues. PMID- 1419315 TI - [The gastrointestinal immune system]. PMID- 1419316 TI - [Esophageal involvement in Behcet's disease]. AB - We report the case of a female patient that fulfills major criteria of Behcet's disease. Multiple esophageal aphthous ulcers seen by endoscopy responded to therapy with steroids and colchicine. PMID- 1419317 TI - [A primary gastric Burkitt's lymphoma in a child]. AB - We report a case of a primary gastric Burkitt's lymphoma in a 8-year-old child, which first symptoms were abdominal pain, dysphagia, melena and a constitutional syndrome. The differential characteristics of this case are its peculiar gastric infiltration and the existence of oesophageal extension, which is very infrequent among this kind of tumors. PMID- 1419318 TI - [An inflammatory fibroid polyp (eosinophilic granuloma) and Crohn's disease located in the ileum]. AB - Lower gastrointestinal tract bleeding as a manner of presentation of the Crohn's disease is uncommon. In most cases there is an other concomitant pathology responsible for that bleeding. We report a case of lower gastrointestinal tract bleeding to an inflammatory fibroid bowel polyp in a patient with ileal Crohn's disease. A commentary is made about the etiopathogenic factors of the both diseases. PMID- 1419319 TI - [Hepatic fascioliasis. Resistance to praziquantel treatment and the radiological findings]. AB - We report a case of hepatic fascioliasis. Fever and epigastric pain was the clinical presentation. We describe the features of the ultrasound and computed tomography examination. Symptoms were persistent after praziquantel treatment. Bithionol was effective and cured the patient. PMID- 1419320 TI - [Intracranial metastasis as the first manifestation of a silent colonic carcinoma]. PMID- 1419321 TI - [Obstructive jaundice due to peripancreatic tuberculous adenitis]. PMID- 1419322 TI - [An inflammatory pseudotumor (plasma-cell granuloma) of the greater omentum]. PMID- 1419323 TI - [Xanthoma of the colon]. PMID- 1419324 TI - [Intestinal metastasis of melanoma as the cause of anemia of uncertain origin]. PMID- 1419325 TI - [Cholecystectomy via laparoscopy: one and a half year's experience]. AB - Results of the first 175 laparoscopic cholecystectomies performed at our hospital over the last 18 months were reviewed. In 17 (9.7%) of cases, due to operatory complications, and in some cases due to instrumental deficiencies, we were obliged to perform conventional laparotomy. In 8 patients, we performed simultaneous alternative surgery during laparoscopy. Our results were satisfactory, with no important complications, no re-operations and only 6.2% of minor complications. Hospital stay was low (2.5 days), and after 10 days patients returned to normal life. PMID- 1419326 TI - [100 cases of laparoscopic cholecystectomy]. AB - The first one-hundred cases of laparoscopic cholecystectomy performed in this department are reviewed. The patients are grouped according to the classification of McSherry: type I: 5%; type II: 50%; type III; 27%; and type IV: 18%. Our technique, which is similar to the one of Troidl, except for entry of the number 4 port, is described. The results are analyzed according the classification of Troidl and 83% of the cases had no complications. There were technical incidents which had no repercussion for the patient in 7% of the cases. In 3% of the patients there were minor complications. There was no mortality. PMID- 1419327 TI - [Pancreatic function and morphology in chronic alcoholism with and without cirrhosis]. AB - We have made a prospective study in alcoholic patients, with and without hepatic cirrhosis, in order to evaluate the presence of modifications in the composition of pancreatic juice (JPP) and in the pancreatogram that allows us to diagnose the existence of chronic pancreatitis associated with alcoholic cirrhosis (CE). The patients where 23 chronic alcoholics, 13 of them with CE and the other 10 with no hepatic injury (AC). In all, an endoscopic retrograde cholangiopancreatography (CPRE) was made and after having obtained a pancreatogram a intravenous infusion of secretin and cholecystokinin was performed. The total volume, the concentrations and the out-puts of bicarbonate, amylase, lipase and total proteins were measured in the pancreatic juice collected during 12 minutes. The pancreatogram was normal in the 92.3% of CE and in all the AC. Patients with CE had similar values of all the evaluated parameters to AC patients. In conclusion, there seems to be a good correlation between the pancreatogram and the analytic study of JPP, because the JPP has no qualitative and quantitative anomalies when the Wirsung duct is normal. In our opinion the study of JPP is not useful in the diagnostic of chronic pancreatitis associated with alcoholic hepatic cirrhosis. PMID- 1419329 TI - [The diagnosis of peptic ulcer penetration into the liver by endoscopic biopsy. A report of 2 cases and a review of the literature]. AB - We report two patients and review six additional published cases with liver penetrating peptic ulcer diagnosed by the finding of hepatic tissue in endoscopic biopsies. Clinical and laboratory data were non-specific. The presence of a large (2 cm) gastric or duodenal ulcer, with malignant appearance, or a protruding mass, with secondary ulceration and located in the gastroduodenal posterior wall or in the lesser curvature of the stomach, may suggest the endoscopic diagnosis of this complication. Definitive diagnosis is established by endoscopic biopsies of the ulcer base and/or of the associated mass. PMID- 1419328 TI - [The prediction of the severity of acute pancreatitis by C-reactive protein]. AB - Reactive C Protein (RCP) has been determined in fifty-one patients with acute pancreatitis. RCP has been compared with Ranson's criteria which include several clinical and biochemical parameters. The value of 20 mg/dl is the one which discriminates serious acute pancreatitis from the mild forms in a 84.3% of patients. Sensitivity and specificity of RCP and Ranson's criteria are compared, the results obtained are similar (88.9% vs. 81.8% and 94.4% vs. 97%). In summary, the determination of RCP is very useful for its simplicity and accuracy in the prognosis of acute pancreatitis. PMID- 1419330 TI - [Biliary ascaridiasis]. AB - A case of biliary ascaridiasis is presented in which biliary obstruction and pancreatitis were diagnosed. Recovery followed surgical removal of the worms. The literature is reviewed. PMID- 1419332 TI - II reunion of the National Association for the Study of the Pancreas. Valencia, 6 7 November 1992. Papers and abstracts. PMID- 1419331 TI - [Primary leiomyosarcoma of the gallbladder]. PMID- 1419333 TI - Chronic pancreatitis: diagnosis and medical treatment. PMID- 1419334 TI - Diagnosis and endoscopic treatment of chronic pancreatitis. PMID- 1419335 TI - The pancreas in cystic fibrosis. PMID- 1419336 TI - [A history and prospect of adoptive immunotherapy against malignant glioma--past, now and future]. PMID- 1419337 TI - [The focal brain ischemia with disturbance of venous drainage]. AB - The focal brain ischemia with disturbance of cerebral venous drainage often lead to brain edema and hemorrhagic infarction and make mortality and morbidity worse. So we tried to make sure of this fact using a middle cerebral artery (MCA) occlusion model in adult cat. The MCA was exposed by the transorbital approach and temporally obstructed by Zen's clip. We divided the animals into two groups of eight cats. One group is only MCA occlusion group (sham group) and the other in MCA occlusion with disturbance of venous drainage (VRD group). We ligated bilateral external jugular vein (EJV) and internal jugular vein (IJV) and injected embolic sources from the left EJV to obstruct the venous system of cat brain. The pressure of superior sagittal sinus was increased up to 18.7 +/- 5.3 mmHg by this method. A cranial window was made above the ectosylvian gyrus, which has poor anastomosis. The reactivity of pial arteriole and regional cerebral blood flow (rCBF) were observed through the window. And histological brain examination was also performed. The result was that the reactivity of pial arterioles was severely disturbed in VRD group. The area of cerebral infarction and edema were also significantly expanded in VRD group. Considering from these facts, when the venous drainage was disturbed, cerebral perfusion pressure relatively decrease. Because of the decrease in cerebral perfusion pressure, cerebral infarction and edema probably expand to the area so called penumbra. PMID- 1419338 TI - [Hyponatremia and cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage]. AB - We studied retrospectively the relationship between hyponatremia and cerebral vasospasm in 121 consecutive patients with aneurysmal subarachnoid hemorrhage. In 19 patients sodium levels fell below 130 mEq/l on at least two consecutive days. Hyponatremia developed at average 8.9 hospital day and lasted for 4.4 days. It was mild (126 to 130 mEq/l) in 15 patients, moderate (121 to 125 mEq/l) in 3 patients, and severe (116 to 120 mEq/l) in 1 patient. Cerebral vasospasm was evaluated by angiography, symptoms and CT finding. Angiographical vasospasm was found in 57 patients, symptomatic vasospasm in 38 patients and low density area on CT in 20 patients. Angiographical vasospasm developed in 15 of the 19 patients (78.9%) with hyponatremia, symptomatic vasospasm in 16 patients (84.2%), low density area on CT in 8 patients (42.1%), the difference being significantly high. (respectively, p < 0.01, p < 0.001 and p < 0.01 by chi-square test) Polyuria of 2500 ml or more immediately before the onset of hyponatremia developed in 14 patients (87.5%). When symptomatic vasospasm and hyponatremia coincided, there were only 4 patients in which symptomatic vasospasm was preceded by hyponatremia. So, it is difficult to predict the development of vasospasm from that of hyponatremia. This study found incidence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage to be significantly higher in patients who developed hyponatremia, which raised suspicion about the presence of dehydration. Hyponatremia with central origin generally remains asymptomatic, but it is important to treat positively when the pathology of cerebral vasospasm is taken into consideration. PMID- 1419339 TI - [Perinatal neurosurgical care for one fetal hydrocephalus on twin gestation]. AB - Twin gestations are responsible for a disproportionate amount of perinatal mortality and morbidity. Such gestations may impose greater demands on maternal and child physiologic systems than singleton pregnancies. The most common antenatal complications were preterm labor. The clinical record of myelomeningocele infant presenting with overt hydrocephalus in utero at 27 weeks of twin gestation and operated miniature Ommaya's reservoir placement early after birth and intentional delayed back closure for myelomeningocele was reported. Although perinatal neurosurgical care for one fetal hydrocephalus on twin gestation is clearly advantageous, it alone is relatively ineffective in reducing the incidence of the complication, preterm labor. PMID- 1419340 TI - [Pontine infarction presenting non-paralytic pontine exotropia--evaluation of its clinical course and its MRI findings]. AB - We report two patients with brainstem infarction who presented non-paralytic pontine exotropia (NPPE) in acute phase. Case 1 was a 76-year-old woman. NPPE observed 3 hours after the onset disappeared two days later. Case 2 was a 60-year old man. Paralytic pontine exotropia was observed 4 hours after the onset of his stroke. NPPE was noted on the next day and left medial longitudinal fasciculus (MLF) syndrome was still present on the third day. Seven days later, the disturbances of ocular movement was disappeared. T2-weighted cranial MRI showed high signal intensity lesions in the paramedian portion of the mid-pontine tegmentum beneath the fourth ventricle in both cases. Although it has been thought that NPPE is a rare clinical symptom, we think that NPPE is by no means a rare symptom in the acute stage of brainstem infarction. PMID- 1419341 TI - [A case of general paresis with marked improvement of cerebral blood flow after antiluetic therapy--case report]. AB - Although the incidence of neurosyphilis has declined dramatically after the World War II because of the development of antibiotics, it is recently increasing a little bit. There has been few reports on the neuroimaging of general paresis. We studied a fresh case of general paresis by X-ray CT (XCT), MRI and PET scans, and report the changes of neuroimages before and after the therapy. A 38-year-old man was admitted with disorientation, thought disorder and personality change. He also had insomnia and megalomania. There were neither obvious neurological signs nor particular changes of the XCT scan abnormalities on admission. His clinical symptoms were gradually worsened within three months, when the XCT and MRI scans showed moderate brain atrophy especially in the frontal and temporal lobes with mild dilatation of the lateral ventricles. In the PET study, the cerebral blood flow was decreased in the entire brain, especially in the frontal lobes, although the thalamus and the basal ganglia had normal levels. By immunological procedures and the cerebrospinal fluid (CSF) studies, the diagnosis of general paresis was made. He was treated with penicillin G and other antibiotics. In one year after his first therapy, many symptoms vanished. Although the cerebral atrophy was a little advanced, the cerebral blood flow was dramatically increased. As far as we know, this is the first PET study of general paresis before and after penicillin treatments. PMID- 1419342 TI - [A case of encephalitis with MRI abnormalities localized in the bilateral amygdala and hippocampus]. AB - We report a patient with encephalitis who showed anterograde and retrograde amnesia with MRI abnormalities localized in the bilateral amygdala (AM) and hippocampus (HIPP). A 25-year-old man suddenly experienced a generalized tonic clonic seizure (GTCS). He was admitted because of increasing lethargy with two further GTCSs during the following 6 days. The patient had high fever, and neurological examination revealed somnolence, disorientation, amnesia, and nuchal stiffness. MRI revealed bilateral symmetrical abnormalities localized in the AM and HIPP, which showed low intensity on T1-weighted images and high intensity on T2-weighted images. Cerebrospinal fluid examination showed a mildly elevated cell count. We suspected herpes simplex virus type I encephalitis and began treatment with acyclovir. After the patient regained a clear consciousness, his antero- and retrograde amnesia continued for several months. The MRI abnormality became less distinct with the improvement of amnesia. We consider that the MRI abnormality was indicative of inflammation and edema, and that the lesion in the AM and HIPP had induced the amnesia. PMID- 1419343 TI - [A case of Tolosa-Hunt syndrome accompanied by facial and vestibular nerve damage]. AB - A 37-year old man, who had repeatedly suffered from transient ophthalmoplegia in his left eye at the age of 29 and 36, developed left painful ophthalmoplegia accompanied by ipsilateral facial nerve palsy in August, 1991. Neurological examination revealed involvement of the left oculomotor, trochlear, ophthalmic division of the trigeminal, abducens, facial and vestibular nerves. Gadolinium enhanced MRI which was taken at the acute phase of the illness demonstrated markedly enhanced left cavernous sinus and adjacent thickened dura mater in the middle cranial fossa. At the remission phase after starting corticosteroid therapy, these enhanced lesions were no longer observed even in enhanced MRI studies. We diagnosed him as suffering from Tolosa-Hunt syndrome presently accompanied by facial and vestibular nerve damage because of his history of illness, confined lesion in the left cavernous sinus and steroid-induced remission. We concluded that Tolosa-Hunt syndrome may be accompanied by damage of other cranial nerves in its course and that repeated gadolinium-enhanced MRIs are necessary for diagnosis and observation of the patients. PMID- 1419344 TI - ["Left unilateral agraphia with right hemiparesis" after occlusion of the left middle cerebral artery]. AB - This paper presented a case of a right-handed male who showed a right hemiplegia without aphasia and apraxia. He lost the ability to write with the left hand. A 56-year-old right-handed man, who had a daughter of left-handedness, was sent to our hospital with a homonymous hemianopsia, facial weakness, spastic hemiparesis and sensory disturbance in the right side. CT scan revealed an infarction in the territory of the left middle cerebral artery. On a month after the onset, he was alert and oriented. His speech was normal and verbal comprehension was intact. Although he neglected the right side of the page, he could read and comprehend it correctly. In contrast with his normal abilities to speak, comprehend, and read, difficulties in writing were prominent. Spontaneous writing with the left hand was extremely poor, and he even had difficulty writing his own name. His dictation was also poor, but his writing improved with copying letters. Agraphia had seen even after USN was recovered. Analysis of this case suggested the presence of the dominance for speech, comprehension, and praxis in the intact right hemisphere, and writing center in the damaged left hemisphere. PMID- 1419345 TI - [Hallucinose pedonculaire with left MLF syndrome caused by midbrain infarction--a case report]. AB - A 65-year-old male suffering from left MLF syndrome accompanied by transient hallucinose pedonculaire caused by the midbrain infarction is reported. In the first night of his admission with MLF syndrome, he complained of sleeplessness followed by transient visual hallucination. The hallucination was vivid and colored scene in which many strangers were seen around the patient, and he was well oriented without dreadfulness at that time. A small infarction in the left tegmentum was revealed by MR imaging, which was supposed to cause the hallucination. PMID- 1419346 TI - [Anti-ganglioside antibodies and motor neuropathy in relation to nerve conduction block]. PMID- 1419347 TI - [New methods of estimation of nerve conduction velocity distribution]. PMID- 1419348 TI - [Chronic inflammatory demyelinating polyneuropathy: multifocal demyelinating neuropathy]. PMID- 1419349 TI - [Kainic acid-induced generalized seizures in cats--microinjection into caudate nucleus]. AB - Electroencephalographic and behavioral changes were observed after 2 micrograms of kainic acid (KA) injection through a chronically implanted cannula into unilateral caudate nucleus (CN) of freely moving and non-anesthetized cats. The control group showed no changes on EEG or behavior during the observation period. In KA group, from 2 to 5 minutes after KA injection, the cats showed contralateral circling. On EEG, focal spikes were elicited at the injected site of the right CN. From 15 to 25 minutes after the injection, secondarily generalized seizures were observed on EEG repeatedly. However, the behavioral change was not remarkable and only the behavioral arrest was observed during the electrographic generalized seizure. From 6 to 8 hours after injection, they showed clonic seizure of the contralateral hindlimb followed by generalized tonic clonic convulsion. These seizures were frequent during 6 to 16 hours after injection. However, these seizures subsided within 48 hours after the injection and the cats became normal afterward. Histopathological examination revealed focal pyknosis and gliosis only at the injection site of caudate nucleus. The results suggested that an epileptogenic focus of the caudate nucleus demonstrated a rapid evolution from the focal seizure status to the secondarily generalized seizure status. This fact explains that the caudate nucleus may be a possible key structure as a relay nucleus for the secondary generalization of a focal seizure. PMID- 1419350 TI - [Epidemiological study of motor neuron disease in Hokkaido island--its incidence, prevalence and regional distributions--ALS Study Group]. AB - The incidence, prevalence and regional distributions of sporadic motor neuron disease (MND) from 1980 through 1989 were evaluated in collaboration with multiple neurological institutes in Hokkaido island. Patients with sporadic MND were collected from three sources: 1) neurologist practicing in Hokkaido island, 2) sending inquiries to 620 major hospitals, 3) notification file of MND provided by Japanese Ministry of Welfare and Health. Three hundred and eighty-nine patients with sporadic MND were ascertained for this study. Of 389 patients, 238 patients were men and 151 patients were women, and the ratio of men to women was 1.6:1. The mean age of onset was 58.2 +/- 10.3 years old, 57.7 +/- 10.4 for men and 58.9 +/- 10.0 for women. Their clinical presentations were 303 patients with ALS, 52 patients were PBP and 34 patients were SPMA. The crude incidence rate for both sexes combined for 1980 through 1989 was estimated as 0.69 per 100,000 person-year. The age- and sex-adjusted incidence for men was 0.86 per 100,000 person-year (95% CI, 0.75 to 0.97) and that is higher than 0.53 per 100,000 person-year (95% CI, 0.45 to 0.61) for women. The average, crude prevalence rate from 1985 through 1989 was estimated as 2.25 per 100,000 person-year. There are no overall trends of changing the pattern in incidence and prevalence of MND in Hokkaido island, however the geographic distributions of the incidence of MND according to towns and cities disclosed the presence of some relative clustering areas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419351 TI - [Ruptured aneurysm at the peripheral branch of the posterior cerebral artery with systemic lupus erythematosus]. AB - We report a 73-year-old woman with systemic lupus erythematosus (SLE) in whom intracerebral and intraventricular hemorrhage developed secondary to a ruptured aneurysm on the peripheral branch of the posterior cerebral artery. We reviewed data on 22 patients (43 aneurysms) in previous reports of ruptured cerebral aneurysms associated with SLE, including our case. Of these aneurysms, 34 (79.1%) were located on the major artery, and 9 (20.9%) were located on the peripheral small artery. Fusiform aneurysms accounted for 27.9% of the total. The prognosis was poor, and 14 patients (63.6%) died. Direct aneurysmal surgery was performed in 11 patients (50%), but 4 patients died of other diseases associated with SLE. PMID- 1419352 TI - [Studies on the erythrocyte membrane skeleton in a patient with chorea acanthocytosis--theoretical speculation on the mechanism of neurological involvement]. AB - Patients with chorea-acanthocytosis exhibit symptoms of self-biting, choreic movement, and acanthocytosis, but not dementia. The mechanism of choreic movements is still unknown. In order to clarify the etiologic mechanism underlying these movements, we evaluated the erythrocyte membrane in one patient with chorea-acanthocytosis. A 35-year-old female was admitted to Saitama Medical School Hospital because of involuntary movements. She was alert, well-oriented, and had no gross memory defects. She had slurred speech, choreic movements and lip biting. Laboratory examination showed acanthocytes in her peripheral red blood cells, normal serum lipid values, and caudate atrophy on her brain CT scan. In analyzing the acanthocytes, we initially evaluated the size of the acanthocyte population by incubating her red blood cells with plasma. The cell population approximately doubled after 2 hours incubation. Next we examined the protein composition of erythrocyte ghost by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). There was no significant difference between the patient's erythrocyte ghosts and those of a control. Then we investigated morphological changes in the patient's erythrocyte by scanning and transmission electron microscopy (SEM and TEM). SEM showed the typical acanthocyte shape. The quick-freeze, freeze-substitution method confirmed that the routine TEM section was not artifactual, and was in fact in accurate reflection of the actual features of acanthocytes. TEM of the sections prepared from erythrocyte ghosts demonstrated that spectrin tended to be accumulated in the thorn region. Furthermore, TEM of quick-freeze, deep-etched replica of the ghost revealed more clearly a spectrin network densely packed on the inner hydrophilic surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419353 TI - [Immunohistochemical and clinicoendocrinological studies of gonadotropin producing pituitary adenomas]. AB - In order to study the secretion of gonadotropins in clinically non-functioning pituitary adenomas, 83 cases were investigated by immunohistochemistry. Expression of one or more of gonadotropin subunits (alpha-subunit, follicle stimulating hormone (FSH) beta, luteinizing hormone (LH) beta) was found in 38 (45.8%) of all adenomas studied. alpha subunit and FSH beta were positive in 28 (33.7%) and 27 (32.5%) cases respectively, whereas LH beta was detected in seven (8.4%) adenomas. The presence of both alpha subunit and FSH beta was found in 17 cases, while alpha subunit was singly positive in 11 cases and FSH beta, in 10 cases. LH beta was not detected alone, but was always accompanied by alpha subunit or FSH beta. By the double staining method, alpha subunit and FSH beta were not always colocalized in the same cells. Some cells were found to contain both alpha subunit and FSH beta, but others contained either alpha subunit or FSH beta. Clinical characteristics of gonadotropin positive adenomas (38 cases) were studied in comparison with null cell adenomas (37 cases), which were negative for all anterior pituitary hormones. The former (male 27, female 11) ranged in age from 21-74 years old (mean, 46.5 yr.), and the latter (male 16, female 21) from 28-68 yr (mean, 49.5 yr.). Gonadotropin positive adenomas tended to occur in middle-aged men. All 38 adenomas were macroadenomas, and 29 patients complained of visual failure. Clinical symptoms accompanied by hypersecretion of FSH was infrequent. Hypogonadism (amenorrhea, galactorrhea, loss of libido) were observed in 8 (9.6%) cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419354 TI - Inositol phosphates and calcium signaling. PMID- 1419355 TI - Discovery of the InsP3-Ca2+ pathway. A personal reflection. PMID- 1419356 TI - Kinetics of inositol 1,4,5-trisphosphate-stimulated Ca2+ mobilization. PMID- 1419358 TI - Inositol trisphosphate and calcium oscillations. PMID- 1419357 TI - Cellular sites of IP3 action. PMID- 1419359 TI - Spatial organization of Ca2+ signalling and Ins(1,4,5)P3 action. PMID- 1419360 TI - Function and organization of the inositol 1,4,5-trisphosphate-sensitive calcium pool. PMID- 1419361 TI - The role of inositol phosphates in neuronal function. PMID- 1419362 TI - Multiple forms of phospholipase C isozymes and their activation mechanisms. PMID- 1419363 TI - The ins and outs of Ca2+ in exocrine cells. PMID- 1419364 TI - Inositol phosphates. Metabolism and site of action in neutrophil granulocytes. PMID- 1419365 TI - Pressure ulcers, Part two: Management strategies. AB - The goal of this article is to facilitate the successful resolution of pressure ulcers. The nurse practitioner (NP) is an ideal health care professional to manage pressure ulcer care. This article reviews the basic principles related to wound care. The healing trajectory is discussed to assist an NP to determine appropriate therapy. Current, research-based management strategies are provided. PMID- 1419366 TI - The role of the nurse practitioner in adult day care. AB - During the past 25 years, nurse practitioners (NPs) have become health care providers in a variety of settings. Adult day care is one of the settings in which it is increasingly clear that there is a role for the NP. Nurse practitioners have the potential to provide increased comprehensive primary health care to clients participating in these programs. PMID- 1419367 TI - Stress and tobacco addiction. AB - Primary care providers are confronted on a daily basis with persons who are addicted to tobacco. Research studies have demonstrated an association between substance use and stress and coping. This paper discusses macro- and micro-level perspectives of stress that need to be considered in the management of tobacco addition. Lazarus's stress and coping paradigm is emphasized as a useful framework for managing addicted clients. PMID- 1419368 TI - The health beliefs and practices of an Old Order Amish family. AB - In caring for people from different cultures, it is important that nurses acknowledge the health beliefs and practices of clients. The purpose of this case study was to describe the health beliefs and practices of one Old Order Amish family. The study was conducted by interviewing a Lancaster County, Pennsylvania, Old Order Amish family. The data focused on five areas of inquiry: (a) care of elderly family members, (b) health practices, (c) home births, (d) death, and (e) health insurance. This study revealed that the Old Order Amish have health beliefs and practices that are unique to their culture. PMID- 1419369 TI - A new look at pharmacologic therapy for adult asthma. AB - Antiinflammatory agents in conjunction with beta agonists in the form of inhaler cromolyn or steroids are currently the cornerstone of therapy for recurrent asthma after the patient has failed on beta agonists alone. Early treatment with antiinflammatory agents is strongly recommended, and may prevent irreversible airflow obstruction caused by chronic inflammation, reducing the mortality from this illness. PMID- 1419370 TI - Current trends in history taking and physical examination: teaching dentists physical assessment. PMID- 1419371 TI - The status of Medicare reimbursement for nurse practitioners. PMID- 1419372 TI - Directory of Academy Board of Directors. July 1992--July 1993. PMID- 1419373 TI - Provision of health care in a frontier setting: an Alaskan perspective. AB - The Community Health Aide Program is the Indian Health Service's answer to to the provision of care to 45,000 Alaska Native people living in remote areas of the state. Community health aides are local people who live and work in their villages. They offer health services from emergency to preventative care with the help of their referral physician, who may be up to 1,300 miles away. Nurse practitioners play an important role in the training and supervision of community health aides. This article gives an overview of the program, its successes and problems, with implications as a health care delivery model for care in other underserved areas of the United States. PMID- 1419374 TI - Reducing children's pain-distress associated with injections using cold: a pilot study. AB - This study used an experimental design to test the question, "Does ice reduce the pain-distress children experience with injections?" One half of the 38 preschool children had ice applied to the preimmunization site for 30 seconds. The remaining children received the injection without the extra intervention. Measures included the Global Mood Scale, pulse rate, Oucher scale, and Faces scale. The results failed to show that ice reduces children's pain-distress with injections. Reasons for the failure are discussed, with comments on the various measures and suggestions for further study in this area of child nursing care. PMID- 1419375 TI - Oral tiludronate: pharmacological properties and potential usefulness in Paget's disease of bone and osteoporosis. PMID- 1419376 TI - The number of fibroblastic colonies formed from bone marrow is decreased and the in vitro proliferation rate of trabecular bone cells increased in aged rats. AB - Four- and 21-month old female Sprague-Dawley rats were sacrificed and their tibiae and femurs isolated for histology and initiation of bone marrow and trabecular bone cultures. The bone loss observed in 21-month old rats was associated with a markedly decreased osteoblastic index. The percentages of mineralizing trabecular surfaces were only slightly decreased in aged rats, whereas the percentages of mineralizing endocortical surfaces were strikingly decreased. Diaphyseal femoral marrows from 21-month old rats were less cellular than those from four-month old rats, and developed in culture fewer fibroblast colony forming units (FCFU) and fewer adherent cells with phenotypic characteristics of osteoblast-like cells. Trabecular bone cultures from 21-month old rats produced as many cells as cultures from four-month old rats, whereas the amount of trabeculae put into culture was much less in aged rats. Moreover, the proliferation rate in secondary culture was significantly increased in 21-month old rats. Similar responses to calcitriol were observed in bone marrow and trabecular bone cells from aged and younger mature rats, while cAMP responses to PTH were decreased in cells from aged rats. Our data confirm the age-related decrease in the FCFU efficiency of the bone marrow and show a stimulated proliferation of trabecular bone cultures from 21-month old rats that could be seen either as the result of the inhibition in vivo of the response to a signal to proliferate, or as a rebound response to factors present in the serum-enriched medium and lacking in vivo. PMID- 1419377 TI - A quantitative evaluation of osteoblast-osteocyte relationships on growing endosteal surface of rabbit tibiae. AB - Scanning electron microscopy (SEM) was used to quantify the intercellular relationships between osteoblasts and osteocytes on the growing endosteal surfaces of the medullary canal of the tibia in four rabbits of different ages. The area of each osteoblast was measured on the SEM micrographs by means of an Image Analyzer. The number of osteocyte cytoplasmic processes was indirectly evaluated by counting the canalicular openings present on the same microscopic fields after the removal of the osteoblasts. The metabolic activity of the osteoblasts was indirectly evaluated from their shape, and the structure was analyzed by transmission electron microscope (TEM) in sections taken from the samples studied by SEM. In all four animals, the surface area of the osteoblasts (OA) was found to vary a great deal, whereas the density of canalicular openings was fairly uniform. Moreover, although the OA mean value increases significantly with the age of the animals, the density of canalicular openings does not; it would therefore appear that the older the animal and the more flattened the osteoblasts, the greater the number of canaliculi beneath them. Since osteoblast activity has previously been shown to be inversely proportional to the area of the protoplasm in contact with the bone surface, it appears that the less active osteoblasts should contact a greater number of osteocyte cytoplasmic processes. These findings suggest that osteocytes might play an important role in modulating osteoblast activity and in recruiting osteoblasts that differentiate into osteocytes, possibly by means of inhibitory signals transmitted via gap junctions. PMID- 1419378 TI - Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients. AB - An increasing body of experimental data suggests a role for 24,25(OH)2D3 in bone metabolism. The present study was carried out to assess a possible therapeutic role of this vitamin D metabolite in renal osteodystrophy. Twenty-two chronic dialysis patients, most of whom were previously maintained on 1 alpha (OH)D3 therapy, received additional treatment with 10 micrograms/day 24,25(OH)2D3 and were compared to 19 patients receiving 1 alpha (OH)D3 alone. Analysis of transiliac bone biopsies obtained at study entry and following 10-16 months of treatment revealed that the combined therapy produced a decrease in bone turnover. Specifically, the addition of 24,25(OH)2D3 inhibited an increase in trabecular bone volume (BV/TV) and suppressed osteoclastic parameters. Thus BV/TV increased from 26.2 +/- 8.6 to 32.1 +/- 7.5% (p < 0.01) in the 1 alpha (OH)D3 group, but it remained unchanged in the combined therapy group. In contrast, the eroded surface (ES/BS), the osteoclast surface (Oc.S/BS), and the osteoclast numbers were significantly suppressed in patients receiving both 24,25(OH)2D3 and 1 alpha (OH)D3, as compared with those receiving 1 alpha (OH)D3 alone (p < 0.01, p < 0.01, and p < 0.001, respectively). These improvements were independent of changes in 1 alpha (OH)D3 dosage. The extent of bone aluminium deposits was unrelated to the administration of 24,25(OH)2D3 or to its effect. 24,25(OH)2D3 therapy was not associated with any adverse effects. PMID- 1419379 TI - Effects of gallium nitrate on calcium transients in UMR-106 rat osteoblastic osteosarcoma cells. AB - Gallium nitrate is an effective antihypercalcemic and antiresorptive agent. Although its effects on osteoclasts are well documented, the mechanism of action of gallium nitrate on osteoblasts is still not established. To determine the effects of gallium nitrate on calcium signalling, we studied its effects on intracellular calcium concentration in UMR-106 rat osteoblastic osteosarcoma cell line. Cells were loaded with a calcium binding fluorescent dye, fluo-3. Changes in fluorescence reflected changes in cytosolic calcium. Gallium nitrate elicited a dose-dependent biphasic calcium transient with an initial decrease followed by an increase, and these changes were seen at high extracellular calcium concentration. Markedly altered signal was seen in nominal calcium-free medium, suggesting that gallium nitrate mobilized calcium only partly from intracellular stores. Gallium nitrate, at concentrations as low as 3 micrograms/ml, inhibited parathyroid hormone-stimulated calcium transients. High doses of parathyroid hormone could overcome this inhibition. This inhibitory effect appears to be selective, since gallium nitrate did not prevent calcium transients elicited by alpha-thrombin or prostaglandin F1 alpha. Failure of gallium nitrate to prevent calcium transients elicited by these agents, even after the inhibition of parathyroid hormone-induced signal, indicates that the inhibition is not a toxic effect. In conclusion, gallium nitrate has a marked effect on calcium signalling in UMR-106 cells that might be of major importance in modifying the effects of calcemic hormones or local factors on osteoblasts. PMID- 1419380 TI - Osteogenic activity of growth cartilage examined by implanting decalcified or devitalized ribs and costal cartilage zone, and living growth cartilage cells. AB - The formation of cartilage prior to bone in an endochondral bone formation process suggests that some osteogenic factors exist in the cartilage. This osteogenic activity of cartilage or cartilage cells was examined by implanting ribs and costal cartilage zone into a subcutaneous pocket of abdominal wall, or the growth cartilage (GC) cells into a peritoneal cavity. Rib segments of young (four-week-old) rabbits and rats were decalcified (DCed) in 0.6 N HCl for 24 h at 4 degrees C, or devitalized (DVed) by freezing/thawing and submerged in water for 48 h at 4 degrees C. These specimens were implanted into the subcutaneous pocket of abdominal wall of eight-week-old rabbits and rats. Both the DCed ribs and the DVed ones formed bone at costal GC zone after four to six weeks. Costal cartilage zone of young rabbits and rats was DCed or DVed as stated above, and implanted into the subcutaneous pocket of abdominal wall of eight-week-old rabbits and rats. The DVed costal cartilage zone specimens formed bone after three to four weeks, but the DCed ones did not, even after eight weeks. GC cells were dissociated enzymatically from rat costal GC zone, centrifuged to be made into pellets (5 x 10(5) cells/pellet), and implanted into the peritoneal cavity of eight-week-old syngeneic rats. After four weeks, implanted GC cells formed bone. These results suggest that there are some osteogenic factors in the GC zone produced by GC cells, whose activity is lost by decalcification, and which are different from known BMPs. PMID- 1419381 TI - Regulation of prostaglandin E2 production by vitamin D metabolites in growth zone and resting zone chondrocyte cultures is dependent on cell maturation. AB - The production of PGE2 by chondrocytes and its regulation by vitamin D metabolites was examined in this study as a function of cell maturation. Costochondral chondrocytes, derived from the resting zone and growth zone cartilage, were grown in culture to fourth passage. At confluence, they were exposed to 10(-8)-10(-11)M 1,25-(OH)2D3 or to 10(-7)-10(-10)M 24,25-(OH)2D3 for either five minutes or 3, 6, 12, or 24 hours. Indomethacin (10(-7)M) was added to one-half of the cultures to block the production of PGE2. The amount of PGE2 released into the media was determined by radioimmunoassay. Both growth zone and resting zone cells produced PGE2 in a time-dependent manner; PGE2 concentration was greater in the resting zone cell cultures. 1,25-(OH)2D3 stimulated PGE2 production by growth zone cells in a dose-dependent manner, significant at 10(-8) 10(-10)M. This effect was observed at 3 hours and remained elevated during the 24 hours of culture. 1,25-(OH)2D3 had no effect on PGE2 production by resting zone cells. However, 24,25-(OH)2D3 (10(-7)-10(-8)M) inhibited PGE2 production from 3 24 hours. No effect was noted when 24,25-(OH)2D3 was added to growth zone cells. Indomethacin reduced PGE2 production to baseline values in all groups examined. The results indicate that chondrocytes in culture produce PGE2. Production is regulated by vitamin D3 metabolites and is cell maturation-dependent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419382 TI - 'Fee crisis'. PMID- 1419383 TI - 'Transmission of HIV to dental patients: more data'. PMID- 1419384 TI - 'Selection criteria for dental radiography'. PMID- 1419385 TI - Mercury from dental amalgam. PMID- 1419386 TI - Trends in the incidence of histologically diagnosed intra-oral squamous cell carcinoma in Northern Ireland, 1975-89. AB - Studies in Britain point to a rise in the incidence of intra-oral cancer in the last 20 years, paralleling trends evident in other European countries. Cases of histologically-diagnosed primary intra-oral squamous cell carcinoma have been ascertained by reviewing the records of pathology departments in Northern Ireland. Trends in the incidence of the disease have been determined for the period 1975-89. There has been a significant increase in the incidence among men, rising from 1.78 to 3.14 per 100,000. In women over the same period the incidence rose from 0.87 to 1.19 per 100,000, but this change was not significant. These trends concur with recent findings from other countries. PMID- 1419387 TI - The influence of examination frequency and changing dentist on dental treatment provision in an Australian defence force population. AB - During the early 1980s, a number of studies into dental treatment provision in the General Dental Service were conducted in Scotland. These studies indicated that the frequency with which an individual attended the dentist for treatment, or changed their dentist, influenced the amount of dental treatment that they received. The present study was designed to test these findings in an independent population, in this case, 100 members of the Royal Australian Air Force. While the frequency of attending the dentist did not have any significant effect on restoration longevity or the number of restorations a subject received, it did influence the cost of such treatment, indicating that frequent attenders received more expensive treatments rather than more treatment. Changing dentist did not display any significant influence on any of the parameters used in the present study. PMID- 1419388 TI - Evidence of tooth extraction in a Cypriot mandible of the Hellenistic or early Roman period, c. 150 BC to 100 AD. PMID- 1419389 TI - The future of dentistry. PMID- 1419390 TI - A sore in search of a surname. PMID- 1419391 TI - [Burn injuries. Mapping of wound infection--a link in quality assurance activities]. PMID- 1419392 TI - [Life and death. How long can we live?]. PMID- 1419393 TI - [Life and death. Ethics at life's end]. PMID- 1419394 TI - [To discontinue or not to start medical treatment]. PMID- 1419395 TI - [Starting and stopping of life support care]. PMID- 1419396 TI - [Life and death. Interaction with relatives]. PMID- 1419397 TI - [Life and death. Care of the dead person]. PMID- 1419398 TI - [A safe birth]. PMID- 1419399 TI - [Diagnosis based on infant crying. Interview by Ase Dragland]. PMID- 1419400 TI - [Breast feeding before and at present]. PMID- 1419402 TI - [Practice in education. Role of the liaison nurse--research from Oppland on practice in education]. PMID- 1419401 TI - [Project nursing plan: joint documentation system for nursing personnel]. PMID- 1419403 TI - [Practice in education. Liaison nurse--a bridge builder]. PMID- 1419404 TI - [Practice in education. Students as a resource]. PMID- 1419405 TI - [Quality of life--just nurses' responsibility?]. PMID- 1419406 TI - [Rehabilitation--patients with multiple trauma]. PMID- 1419407 TI - [Priests as health care workers]. PMID- 1419408 TI - [Small hospital]. PMID- 1419409 TI - [Burn injuries. Pain management]. PMID- 1419410 TI - [In the sunset of life. Experiences put in a system]. PMID- 1419411 TI - [In the sunset of life. Senile dementia--acting out behavior]. PMID- 1419412 TI - [In the sunset of life. Restless elderly with senile dementia]. PMID- 1419413 TI - [In the sunset of life. Contact telephone for relatives]. PMID- 1419414 TI - [In the sunset of life. To be useful. Interview by Siv Barstad]. PMID- 1419415 TI - [In the sunset of life. When memory fails]. PMID- 1419417 TI - [Interaction with relatives]. PMID- 1419416 TI - [Comments on "Interaction with relatives"]. PMID- 1419418 TI - [Theme "Burn injuries"--correction and addition]. PMID- 1419419 TI - [Paradoxes in nursing]. PMID- 1419420 TI - [In the sunset of life. Loneliness and fellowship]. PMID- 1419421 TI - [Why do we have that today?]. PMID- 1419422 TI - [Primary nursing--group nursing. Are organizational models important for quality in nursing care?]. PMID- 1419423 TI - [Philosophical basis for nursing services in an acute hospital]. PMID- 1419424 TI - [Clinical continuing education--what is nurses' motivation?]. PMID- 1419425 TI - [In the sunset of life. Significance of life's history]. PMID- 1419427 TI - [Home and nursing home--filling a void. Interview by Siv Barstad]. PMID- 1419426 TI - [Home and nursing home--cold coffee and bananas]. PMID- 1419428 TI - ["Created in our image". Interview by Siv Barstad]. PMID- 1419429 TI - [Nurses with nursing assistants' salary]. PMID- 1419430 TI - [Quo vadis--home care nursing?]. PMID- 1419431 TI - [Determine rotation period self]. PMID- 1419432 TI - [Many want to leave]. PMID- 1419433 TI - Synthesis, NMR spectra and function of peptides with alpha-methylserine attached to the RGD sequence of osteopontin. AB - The three-dimensional structure of the RGD-adhesion sequence has been studied previously by means of linear and cyclic peptides. These peptides show widely differing affinities to integrins, ascribed to a strong dependence on steric factors in the receptor recognition. Insertion of alpha-methylserine next to the RGD sequence in this investigation resulted in lower affinity for both stereoisomers, and several small changes in chemical shifts and coupling constants relative to the parent serine peptide GRGDSL. PMID- 1419434 TI - Palladium-catalyzed intramolecular cyclization of vinyl and aryl triflates. Associated regioselectivity of the beta-hydride elimination step. AB - The Pd(0)-catalyzed intramolecular olefination of vinyl and aryl triflates has been studied with a view to gaining insight into the question of kinetically preferred reductive elimination when at least two options are available. In either series, a non-activated alkene participant was found to be converted most readily into the non-conjugated cyclization product. This trend is seen despite the more forcing conditions necessary to engage the less reactive aryl triflates in ring closure. On the other hand, when the pendant chain is terminated by an alpha-methyl acrylate unit, the conjugated diene is kinetically preferred. The two reactions appear to be closely balanced energetically since product distributions are not greatly disparate. Nevertheless, their complementarity could be utilized to advantage in the synthesis of polycyclic molecules possessing multiple sterogenic centers. PMID- 1419435 TI - Pyridine-substituted hydroxythiophenes. I. Preparation of o-(2-, 3- and 4 pyridyl)-3-hydroxythiophenes. AB - 2-(2-, 3- and 4-pyridyl)-3-hydroxythiophenes and 4-(2-, 3- and 4-pyridyl)- 3 hydroxythiophenes have been prepared by hydrogen peroxide oxidation of the corresponding boronic esters. In the former case the boronic esters were obtained in three steps from 2,3-dibromothiophene via the corresponding 3-bromo-2 pyridylthiophenes synthesized by Pd(0)-catalyzed coupling between 3-bromo-2 trimethylstannylthiophene and the corresponding bromopyridines. In the latter case the known isomeric pyridylthiophenes were converted into the corresponding boronic esters in three steps via tribromo- and 3-bromo-4-pyridylthiophenes successively. 4-(3- and 4-pyridyl) thiophen-2(5H)-ones were also obtained in the syntheses of 4-(3- and 4-pyridyl)-3-hydroxythiophene. They are suggested to arise from rearrangement during the halogen-metal exchange. Spectroscopic investigations by 1H NMR and IR show that these hydroxythiophene systems exist exclusively as enol forms. PMID- 1419436 TI - Biosynthetic studies of marine lipids. 40. Generation of the cyclopropane ring of sormosterol. PMID- 1419437 TI - Interleukin-6 and the metabolic response to surgery. PMID- 1419438 TI - A new look at the breath of life. PMID- 1419439 TI - Metabolic and respiratory changes after cholecystectomy performed via laparotomy or laparoscopy. AB - We have compared metabolic and respiratory changes after laparoscopic cholecystectomy (n = 15) with those after open cholecystectomy (n = 15). The durations of postoperative i.v. therapy, fasting and hospital stay were significantly shorter in the laparoscopy group. During the first and second days after operation, analgesic consumption but not pain scores (visual analogue scale) were significantly smaller after laparoscopy, while vital capacity, forced expiratory volume in 1 s, and PaO2 were significantly greater. The metabolic and acute phase responses (glucose, leucocytosis, C-reactive protein) were less after laparoscopy compared with laparotomy. Although plasma cortisol and catecholamine concentrations were not significantly different between the two groups, after surgery interleukin-6 concentrations were less in the laparoscopy group. PMID- 1419440 TI - Effect of the laryngeal mask airway on lower oesophageal sphincter pressure in patients during general anaesthesia. AB - We have studied the tone of the lower oesophageal sphincter (LOS) in 40 adults undergoing routine body surface surgery and allocated randomly to receive anaesthesia either by face mask and Guedel airway or by laryngeal mask airway. In the laryngeal mask group there was a mean (SEM) decrease in barrier pressure (LOS minus gastric pressure) of 3.6 (1.4) cm H2O, compared with a mean increase of 2.2 (1.2) cm H2O in the face mask group (P < 0.005). PMID- 1419441 TI - Anaesthesia for transthoracic endoscopic sympathectomy in the treatment of upper limb hyperhidrosis. AB - Renewed interest has been shown in transthoracic endoscopic sympathectomy (TES) for the treatment of upper limb hyperhidrosis. We review our experience and discuss the anaesthetic technique and perioperative problems encountered in 58 patients undergoing TES for hyperhidrosis. Patients were monitored for arterial pressure, heart rate, ECG, pulse oximetry (SpO2), end-tidal carbon dioxide concentration, peak inspired airway pressure and skin temperature. General anaesthesia, with a double-lumen endobronchial tube, enabled the lungs to be collapsed alternately, thereby ensuring easy and clear access to the sympathetic chain. Controlled ventilation with 100% inspired oxygen was necessary to obviate hypoxaemia. In two patients, severe hypotension and bradycardia occurred during insufflation of carbon dioxide into the chest cavity. Four patients required underwater drainage of the pleural cavity for treatment of pneumothorax or haemothorax. The success and safety of the procedure depends on a scrupulous anaesthetic technique. PMID- 1419442 TI - Perioperative continuous monitoring of ST-segment changes in patients undergoing elective caesarean section. AB - Using continuous ambulatory electrocardiography, we have investigated the incidence of ST-segment changes occurring in patients undergoing elective Caesarean section under extradural, spinal or general anaesthesia. There was no evidence of significant perioperative ST-segment changes. The findings contrast with the results of other work published recently. PMID- 1419443 TI - EEG burst suppression with propofol during cardiopulmonary bypass in children: a study of the haemodynamic, metabolic and endocrine effects. AB - We have studied the effects of propofol, given to maintain EEG suppression throughout cardiopulmonary bypass (CPB), in 20 children aged 1-15 yr, in a parallel group comparison. Anaesthesia was produced by fentanyl 50 micrograms kg 1, enflurane or halothane and midazolam 0.1 mg kg-1 at the start of CPB. After randomization, 50% of the children also received propofol during CPB. All children were cooled during CPB (25-28 degrees C) and pump flows (non-pulsatile) were 2.4 litre min-1 m-2, reducing to 1.2-1.6 litre min-1 m-2 during hypothermia. Large rates of infusion of propofol were required to maintain EEG suppression, particularly during rewarming. Compared with control, the propofol group showed significant increases in mixed venous oxygen saturation and significant reductions in systemic oxygen uptake and glucose and cortisol concentrations. There were no differences in triiodothyronine and lactate concentrations, mean arterial pressure during CPB and inotrope requirement after CPB, or in recovery times. PMID- 1419444 TI - Infusion of propofol to identify smallest effective doses for induction of anaesthesia in young and elderly patients. AB - We studied 110 patients older than 60 yr or aged 18-50 yr as separate groups in two stages to identify the smallest effective doses of propofol for induction of anaesthesia. In the elderly patients, in stage 1, at infusion rates of 25, 50 or 100 mg min-1 the mean (SD) doses administered were propofol 0.82 (0.14) mg kg-1, 1.22 (0.24) mg kg-1 and 1.65 (0.60) mg kg-1 and the induction times 140.1 (21.9) s, 103.2 (23.5) s and 69.4 (10.0) s, respectively. In stage 2, after induction with a fixed dose of 0.82 mg kg-1 as a bolus over 5 s or as an infusion at 25 mg min-1, the times for induction were 38.5 (14.0) s and 144.5 (36.6) s, respectively. In the young patients, at induction rates of 33.3, 50, 100 or 200 mg min-1, the doses administered were propofol 1.36 (0.28) mg kg-1, 1.46 (0.12) mg kg-1, 1.85 (0.43) mg kg-1 and 2.39 (0.50) mg kg-1 and the induction times 145.0 (25.4) s, 120.0 (18.4) s, 80.2 (19.2) s and 54.5 (10.4) s, respectively. In stage 2, a fixed induction dose of 1.46 mg kg-1 resulted in induction times of 35.0 (8.5) s and 134.0 (26.8) s, respectively. In stage 2 of each age group, induction was achieved with smaller doses than those recommended previously and there was no difference in the number of patients in whom induction of anaesthesia was successful or in the measured cardiorespiratory variables between the two induction regimens. This suggests the latter effects are caused by the dose administered and not the rate of administration. PMID- 1419445 TI - IV bolus administration of subconvulsive doses of lignocaine to conscious sheep: effects on circulatory function. AB - We have studied the effects of subconvulsive doses of lignocaine on circulatory function in five conscious, chronically instrumented sheep. In the absence of overt signs of central nervous system toxicity, 50-, 75- or 100-mg i.v. bolus doses of lignocaine induced reductions in myocardial contractility, as assessed by the maximum rate of increase in left ventricular pressure (LV dP/dtmax), of 17 (SD 4)%, 25 (4)% and 33 (4)%, respectively. The durations of these reductions in myocardial contractility were 2-3.5 min. There were no significant changes in cardiac output, coronary artery blood flow, mean arterial pressure, heart rate or left ventricular systolic and diastolic pressures. It is concluded that the initial toxic effects of lignocaine are on the heart rather than the central nervous system, as is generally believed. This negative inotropic effect of lignocaine in vivo may be more deleterious to myocardial function when the heart is compromised by pre-existing disease, or the co-administration of other myocardial depressive drugs. PMID- 1419446 TI - Effect of graded infusion rates of propofol on regional and global left ventricular function in the dog. AB - We have studied the effects of graded infusion rates of propofol (0.2-0.5 mg kg-1 min-1) on left ventricular global and regional function, in eight acutely instrumented dogs. Global function was assessed by measurement of aortic and left ventricular pressure, LV dP/dtmax, aortic blood acceleration and stroke volume. Regional function was assessed by measurement of systolic shortening and the end systolic pressure-length relationship. The response of the coronary circulation to short periods of occlusion was also assessed. Administration of propofol significantly reduced left ventricular preload, as indicated by reductions in end diastolic pressure and length; contractility was depressed, the depression being greater in the apex than in the base of the left ventricle. High infusion rates impaired relaxation. Regulation of coronary blood flow was not disrupted. Reductions in preload and contractility contributed to the propofol-induced hypotension. After 60 min, recovery from the greatest infusion rate was incomplete. PMID- 1419447 TI - Porcine model for studying the passage of non-depolarizing neuromuscular blockers through the blood-brain barrier. AB - A method has been developed for blood-brain barrier disruption to provide reproducible access to the cerebrospinal fluid of the cerebello-medullary cistern. The technique was used successfully to investigate transfer of pancuronium to the cerebral CSF compartment in pigs. After osmotic disruption of the blood-brain barrier, pancuronium concentrations increased significantly in the cerebrospinal fluid. PMID- 1419448 TI - One-compartment kinetics. AB - The mathematical development of the equations needed to determine the plasma concentrations of drug in a one-compartment pharmacokinetic model are developed from first principles and are illustrated (with caution) by the use of morphine given by bolus or continuous i.v. injection or by a simulated i.m. injection. The equations allow the calculation of concentrations, given a knowledge of what drug is currently present, what are the sizes of the boluses by either i.m. or i.v. injection and what is the constant infusion rate. What happens when changes occur is also illustrated. The development illustrates the principles needed to apply to more complex models. PMID- 1419449 TI - A new technique for two-hand bag valve mask ventilation. AB - A method of bag valve mask ventilation (BVM) in which the resuscitator compresses the self-inflating bag between the open palm and body was compared with both standard single resuscitator and two-resuscitator BVM ventilation. Eighteen subjects ventilated a modified recording manikin using each method in random order. The tidal volume (VT) was greater with the open palm (mean 684 (SD 182) ml) than standard single resuscitator ventilation (mean 520 (152) ml). The difference was greater in the nine subjects with small hands (mean 196 (103) ml). VT was less than with two-resuscitator ventilation (mean VT 953 (236) ml). PMID- 1419450 TI - Topical anaesthesia for extracorporeal shock wave lithotripsy. AB - We have investigated 60 patients in a prospective double-blind, placebo controlled study to assess the efficacy of EMLA (Eutectic Mixture of Local Anaesthetics) cream to provide analgesia during extracorporeal shock wave lithotripsy (ESWL) with a second generation lithotriptor. Before operation, EMLA or placebo cream was applied to the patient's back at the anticipated shock head skin interface. During the procedure increments of fentanyl 0.5 micrograms kg-1 were given i.v. on patient demand. There was no significant difference (P = 0.83) in the dose of fentanyl given to each group. We cannot recommend, therefore, the use of EMLA cream as an analgesic during ESWL with a second generation lithotriptor. PMID- 1419451 TI - Transient bradycardia associated with extradural blood patch after inadvertent dural puncture in parturients. AB - We have studied prospectively 10 ASA I or II postpartum patients after inadvertent dural puncture during labour. An extradural blood patch (autologous blood 15 ml) was performed within 18 h of delivery, with continuous EEG, upper facial EMG (Datex: Anesthesia and Brain Activity Monitor), pulse oximetry and heart rate measurement before, during and for 30 min after extradural injection. Non-invasive arterial pressure measurements (Dinamap) were recorded at 5-min intervals. After extradural blood patch, a statistically significant (Student's t test, P < 0.05) decrease in heart rate, from a mean baseline of 88.6 (SD 7.31) beat min-1 to 51.3 (7.6) beat min-1, occurred within 122.6 (16.9) s from the time of the EBP. Bradycardia was observed for a mean duration of 12.4 (1.1) s. Upper facial EMG, EEG, SpO2 and arterial pressure did not change. PMID- 1419452 TI - Effects of omeprazole, ranitidine, famotidine and placebo on gastric secretion in patients undergoing elective surgery. AB - We have compared the effects of omeprazole, ranitidine, famotidine and placebo on gastric secretion in a double-blind study in 110 patients undergoing elective surgery. Three hours before operation, the patients received, orally, omeprazole 40 mg, ranitidine 150 mg, famotidine 40 mg or placebo. Gastric volume and pH were measured immediately after induction of anaesthesia. Omeprazole, ranitidine and famotidine produced a significant increase in gastric pH and a significant decrease in gastric volume compared with placebo. When the effects of omeprazole on gastric volume were compared with those of ranitidine and famotidine, no significant difference was found, but omeprazole was significantly less effective in increasing gastric pH. The number of patients having a pH less than 2.5 and a volume greater than 0.4 ml kg-1 were: none in the ranitidine group, one (3%) in the famotidine group, four (15%) in the omeprazole group and six (23%) in the placebo group. We conclude that omeprazole 40 mg given 2-4 h before surgery does not afford adequate prophylaxis for the acid aspiration syndrome. PMID- 1419453 TI - Surgical face masks are effective in reducing bacterial contamination caused by dispersal from the upper airway. AB - We have studied the effectiveness of surgical face masks in reducing bacterial contamination of a surface, produced by dispersal of organisms from the upper airway. Twenty-five volunteers were asked to speak at blood agar plates positioned in close proximity to the mouth, initially whilst not wearing a face mask and then wearing a surgical face mask over the mouth and nose. A fresh face mask almost completely abolished bacterial contamination of agar plates 30 cm from the mouth. After 15 min there was an increase in the level of contamination which was statistically insignificant. PMID- 1419454 TI - Influence of cardiac output on the correlation between mixed venous and central venous oxygen saturation. AB - The influence of cardiac output on the correlation between central venous oxygen saturation and mixed venous oxygen saturation was assessed in 51 patients who had both a pulmonary artery catheter and separate central venous catheter in situ. Seventy-six paired samples were taken from the catheters and oxygen saturation measured immediately in a Ciba Corning 2500 Co-oximeter. Cardiac output was measured using a standard thermodilution technique. The data were separated into groups with low cardiac index (< 2.5 litre min-1 m-2; n = 20), medium cardiac index (2.5-4.0 litre min-1 m-2; n = 36) and high cardiac index (> 4.0 litre min-1 m-2; n = 20). The correlation coefficients of the three groups were: low cardiac index 0.95, medium cardiac index 0.88 and high cardiac index 0.95 (P < .001 for all three groups). All measurements were made before any x-ray and necessary repositioning of the central venous catheter. These results suggest that central venous oxygen saturation is a useful estimate of mixed venous oxygen saturation and that the influence of cardiac output on that estimate is minimal. PMID- 1419455 TI - A method to facilitate regional anaesthesia by detection of mixed nerve action potentials. AB - We have studied conduction anaesthesia of the median and ulnar nerves at the axilla using mixed nerve action potentials (MNAP) as a guide to needle position in three volunteers. The median and ulnar nerves were stimulated distally at the wrist using surface electrodes and MNAP were detected proximally in the axilla using an insulated needle electrode. The increase in amplitude of MNAP to maximum as the insulated needle electrode approached the nerve trunk was taken as an indication that the tip of the needle was in close proximity to the nerve trunk. Instillation of 1% lignocaine plain 4 ml decreased the amplitude of the MNAP with the onset of nerve block. We conclude that this method may be of potential use as an aid to peripheral regional anaesthesia by allowing accurate localization of needle position close to specific nerve trunks. PMID- 1419456 TI - Lumbovertebral syndrome after extradural blood patch. AB - We describe a patient who developed an immobilizing lumbovertebral syndrome after an extradural blood patch and who was hospitalized with a suspected extradural abscess. An infectious aetiology of the persistent backache could be excluded and the patient recovered with analgesics and physiotherapy. The probable aetiology is discussed. PMID- 1419457 TI - Accidental subdural catheterization: radiological evidence of a possible mechanism for spinal cord damage. AB - We describe the inadvertent subdural insertion of a lumbar extradural catheter in a primiparous woman in labour. A small quantity of local anaesthetic resulted in extensive motor and sensory block. Computed tomography performed after contrast injection demonstrated unequivocally that the catheter was in the subdural space. The catheter and injected fluid produced considerable displacement of the arachnoid within the thecal sac. We postulate that this could result in arterial compression or direct damage to the spinal nerve roots. Such a mechanism might explain some of the cases of permanent neurological damage associated with extradural analgesia. PMID- 1419458 TI - Life-threatening acute respiratory distress in late pregnancy. AB - Acute severe ventilatory failure from any cause is always a critical emergency. In advanced pregnancy, such an episode is particularly hazardous. The management of a pregnant patient who presented with an acute episode of respiratory distress is described. Although this was though initially to be an asthmatic attack, there was evidence of upper airway obstruction caused by an enlarged thyroid. The major complicating factors and aetiology are discussed. PMID- 1419459 TI - Midazolam and cardioversion. PMID- 1419460 TI - Delayed septicaemia after extradural steroid treatment. PMID- 1419461 TI - Steroid therapy and extradural analgesia. PMID- 1419462 TI - Insulated regional block needles. PMID- 1419463 TI - Effect of preoperative opioid administration on postoperative pain. PMID- 1419464 TI - Unnecessary preoperative investigations in children. PMID- 1419465 TI - Selective activation of extrathymic T cells in the liver by glycyrrhizin. AB - Extrathymic pathways for T cell differentiation were recently demonstrated in the liver, intestine and omentum. In this study, glycyrrhizin (GL), a plant extract was investigated as to its effect on extrathymic T cells in the liver of mice. A new method using anti-LFA-1 mAb in conjunction with anti-TCR or -CD3 mAbs to sensitively identify such extrathymic T cells is included. Single injection and repeated injections of GL increased not only the number of total hepatic MNC but also the proportion of intermediate TCR cells, which are extrathymic T cells uniquely seen in the liver. In contrast to other tested reagents (e.g., lymphotoxin and estrogen) that activated the extrathymic T cells and simultaneously induced profound thymic atrophy, GL did not affect regular T cells in the thymus. The present results suggest that the selective activation of extrathymic T cells in the liver might be intimately related to the clinical effects of GL. PMID- 1419466 TI - The potential improvement of thrombolytic therapy by targeting with bispecific monoclonal antibodies: why they are used and how they are made. AB - The generation of the proteolytic enzyme plasmin from its inactive precursor plasminogen, mediated by so called plasminogen activators, is the essential step in thrombolytic therapy. Plasmin is responsible for the degradation of the insoluble fibrin, the major component of a thrombus, to soluble fibrin degradation products. So far, the use of the more recently developed thrombolytic agents single-chain urokinase-type plasminogen activator (scu-PA) and tissue-type plasminogen activator (t-PA) were disappointing, mainly due to some of their negative properties in vivo, i.e., rapid inhibition and/or hepatic clearance. Besides some background information on the haemostatic balance; t-PA and scu-PA structure; and mechanisms of action, we here review some reported attempts to improve on these agents for thrombolytic therapy following various strategies. One of the more potential strategies, antibody-targeted thrombolytic therapy using bispecific monoclonal antibodies, is discussed somewhat more extensively, as are the several procedures that can be followed for bispecific antibody preparation. PMID- 1419467 TI - Chinese medicine, Coix seeds increase peripheral cytotoxic T and NK cells. AB - Coix seeds, a Chinese medicine have been used in Japan and reported to be effective in patients with verruca vulgaris and verrucae planae juveniles. We investigated the in vivo effects on lymphocyte subsets in seven healthy volunteers who took six tablets of Coix seeds three times a day (a typical dose) for four weeks. Leukocyte counts and the percentage of total lymphocytes did not change but the percentages of CD3+CD56+ cells and CD16+CD57- cells increased significantly. These results indicate that Coix seeds increase peripheral cytotoxic lymphocytes and may be effective to viral infection through the enhancement of cytotoxic activity. PMID- 1419468 TI - Early and late hormonal modulation of cholinergic maturation in culture of embryonic mesencephali. AB - Dissociated cells from 13- and 17-day-old embryonic rat mesencephali have grown in primary cultures in order to compare the early and late influences of different agents--insulin, dexamethasone and nerve growth factor (NGF)--on the expression of cholinergic maturation process. We have studied cholin acetyltransferase (ChAT) activity, which is regarded as a specific marker for cholinergic function of the brain, and a widely used differentiation marker, the acetyl-cholinesterase (AchE) enzyme. Biochemical maturation of increasing specific activity of ChAT in both younger and older cells was taken into consideration. During cultivation the AchE activity was slightly increased in younger cells, but a dramatic decrease could be noted in older ones. Insulin in concentration from 10 to 27 micrograms mL-1 causes a significant inhibition in ChAT activity in comparison with the enzyme activity measured in control cultures (insulin ranging from 1 to 100 ng), independently of embryos age. This polypeptide hormone is able to enhance AchE activity in the cultured cells, especially in older ones. With continuous treatment of the culture with dexamethasone, a synthetic glucocorticoid, the ChAT activity in younger cells reaches a maximum curve by day 9 (nine). At this time the AchE activity shows a slighter, no significant increase than at any other time during cultivation. In cell cultures taken from 17-day-old embryos however dexamethasone treatment evoked a significant decrease in ChAT activity with a concomitant increase of AchE activity which was compared to insulin treatment. In spite of the fact that the NGF is able to enhance the ChAT activity, no significant alteration in AchE activity can be measured in younger cell cultures. These results suggest an uneven expression of the enzymes in embryonic rat mesencephali in the presence of above agents depending on the age of cells. PMID- 1419469 TI - Administration of milk from cows immunized with intestinal bacteria protects mice from radiation-induced lethality. AB - Oral administration of "immune milk", that had been obtained from cows immunized with a variety of human gut bacteria containing E. coli, S. typhimurium, S. dysenteriae and 23 others, protected AKR/J mice from the lethal effect of radiation, when immune milk was orally given to mice at 150 g kg-1 day-1 for 7 days prior to gamma-irradiation of 8 Gy. Mean survival times were 24.8 days for the group given immune milk but only 16.8 days for the group given control milk from unimmunized cows. Enterobacteriaceae were detected in various organs such as liver, lung and kidney on day 13 after irradiation, whereas the numbers were significantly fewer in the study group as compared with the control group. And fewer number of intestinal Enterobacteriaceae were detected in the study group compared with the control group prior to irradiation. Immune milk also enhanced the mitogenic response to mesenteric lymph node cells, the redirected cytolytic activity of intestinal intraepithelial lymphocytes to P815 tumor cells with anti CD3 mAb, and in vitro killing activities of the phagocytes in mesenteric lymph nodes to E. coli as compared with control milk. These results suggest that immune milk may reduce the number of bacteria translocating from the intestinal-tract and augment the activities of the gut-associated lymphoid tissues against the invasion of intestinal bacteria, causing protection against the lethal effect of radiation. PMID- 1419470 TI - Systemic IL-1 and adjuvant treatment of an experimental tumor. I. Immune status following tumor rechallenge. AB - Local adjuvant therapy of weakly immunogenic tumors protects against primary tumor challenge. However, this form of therapy does not produce long-lasting immunity to the tumor. In this study, local adjuvant therapy combined with systemic IL-1 administration produced not only primary tumor protection, but also long lasting immunity to the tumor. IL-1 and adjuvant protected animals resisted rechallenge with tumor as much as 180 days after initial tumor administration. Resistance to tumor rechallenge was IL-1 dose dependent. IL-1 and adjuvant protected animals also exhibited delayed type hypersensitivity reactions which were tumor-specific. Splenic and lymph node cell populations from IL-1 and adjuvant protected animals mounted tumor-specific lymphoproliferative responses. No such responses were observed in animals which had been administered either IL 1 or adjuvant alone. These results demonstrate that systemic IL-1 functions to augment specific immune protection when administered in conjunction with local adjuvant, resulting in long-lasting tumor immunity. PMID- 1419471 TI - Therapeutic use of atrial natriuretic factor. PMID- 1419472 TI - Excitatory amino acid antagonists and their potential for the treatment of ischaemic brain damage in man. AB - 1. A wide range of therapeutic strategies has been explored in humans and experimental animals with the aim of improving outcome after brain ischaemia but few have shown convincing clinical benefit. 2. The massive increase in the extracellular concentration of glutamate which occurs in cerebral ischaemia is a key component in the sequence of neurochemical events which leads to neuronal death. Pharmacological blockade of the action of glutamate at the N-methyl-D aspartate (NMDA) receptor, (the glutamate receptor subtype principally involved in the neurotoxic effects of the amino acid) provides a novel therapeutic approach to cerebral ischaemia. 3. The effects of NMDA receptor antagonists in animal models of focal cerebral ischaemia are uniquely consistent, viz, a marked reduction in the amount of irreversible ischaemic damage irrespective of the species, the model of cerebral ischaemia, when the animals are sacrificed after the ischaemic episode, whether ischaemia is permanent or temporary and followed by reperfusion and which particular NMDA antagonist was employed. 4. NMDA receptor antagonists have marked effects on brain function in normal animals. The balance between these potential adverse effects and the anti-ischaemic efficacy of these drugs will ultimately determine the clinical utility of this class of drugs. 5. The data which are reviewed provide the basis for the current clinical evaluation of NMDA receptor antagonists in stroke and head trauma. PMID- 1419473 TI - Studies with low dose intravenous diacid ACE inhibitor (perindoprilat) infusions in normotensive male volunteers. AB - 1. Intravenous ACE inhibitor therapy is of increasing importance in the treatment of patients with unstable heart failure after myocardial infarction. Available pharmacokinetic and concentration effect data with this route of administration are limited. 2. The pharmacokinetics and blood pressure responses to perindoprilat were studied during prolonged low dose (1 mg) infusions in eight normotensive salt replete male volunteers. 3. Subjects received randomised, single (subject) blinded therapy with saline placebo (30 ml) over 3 h or active treatment (1 mg in 30 ml) over 1 h, 3 h or 6 h by constant rate infusion. 4. Significant falls in blood pressure greater than placebo were noted with active infusions without changes in heart rate. Mean maximal plasma perindoprilat concentrations reflected the rate of infusion (1 h, 51.5 +/- 11.4 ng ml-1; 3 h, 30.4 +/- 8.4 ng ml-1; 6 h 19.0 +/- 4.0 ng ml-1) and mean maximal plasma ACE inhibition was less with slower infusions (1 h, 95.7 +/- 0.5%; 3 h 92.3 +/- 2.7%; 6 h 87.4 +/- 5.1%, P less than 0.013). 5. Concentration-time profiles showed a sigmoid drug accumulation profile with delay in the early accumulation of drug particularly during the 3 h and 6 h infusions. The pharmacokinetic data was assessed by statistical comparison of a hierarchy of standard compartmental models and non linear saturable binding models. A non linear model incorporating elements to describe both tissue and plasma binding of the drug provided the best fit to observed data. 6. Low dose constant rate infusions are a means of optimising intravenous ACE inhibitor therapy to allow individual dose titration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419474 TI - The analgesic activity of morphine-6-glucuronide. AB - 1. The pharmacokinetics, cardio-respiratory effects and analgesic effects of intravenous morphine-6-glucuronide were studied in 20 cancer patients with pain. Four different dose levels (0.5, 1, 2, and 4 mg 70 kg-1) were studied. Plasma concentrations of morphine-6-glucuronide were measured for 12 h after dosing. Pulse rate, respiratory rate and blood pressure were monitored, and pain relief was measured using two rating scales and a visual analogue scale. 2. The mean elimination half-life (+/- s.d.) of morphine-6-glucuronide was 3.2 +/- 1.6 h. The mean AUC standardised to a dose of 1 mg 70 kg-1 was 390 +/- 263 nmol l-1 h. Mean morphine-6-glucuronide clearance was 96 +/- 38 ml min-1. There was a direct relationship between morphine-6-glucuronide plasma clearance and calculated creatinine clearance (r = 0.81, P less than 0.001). 38 +/- 22% of the dose of morphine-6-glucuronide was recovered unchanged in the urine in 24 h. No morphine or morphine-3-glucuronide was detected in the plasma or urine of any patient after morphine-6-glucuronide treatment. 3. Morphine-6-glucuronide exerted a useful analgesic effect in 17/19 assessable patients for periods ranging between 2 and 24 h. No correlation was observed between dose or plasma morphine-6 glucuronide concentrations, and duration or degree of analgesia. No clinically significant changes in cardio-respiratory parameters were observed. No patients reported sedation or euphoria. Nausea and vomiting were notably absent in all cases. 4. Morphine-6-glucuronide is an effective and well-tolerated analgesic. It is likely that the majority of the therapeutic benefit of morphine is mediated by morphine-6-glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419475 TI - Passage of S(+) and R(-) gamma-vinyl-GABA across the human isolated perfused placenta. AB - 1. The maternal to foetal transfers of S(+)- and R(-)-gamma-vinyl-GABA (VGB) across the human isolated perfused placenta were low and comparable with those of acidic alpha-amino acids. 2. The placental uptake of the active S(+)-isomer from the maternal circulation exceeded that of the R(-)-isomer and this was reflected by a corresponding difference in placental tissue concentrations. 3. During perfusion with recirculation of the foetal medium, the two enantiomers were present at a similar concentration and did not concentrate in foetal perfusate, indicating that the excess amount of S(+)-VGB cleared from the maternal circulation was not accessible to the foetal perfusate. Furthermore, stable concentrations of both isomers in the foetal perfusate suggested a lack of placental metabolism. 4. Possible explanations of these findings include the operation of a stereoselective sodium-dependent-GABA placental uptake system on the maternal side, similar to that observed in neuronal tissue, or stereoselective binding to a placental GABA transaminase. PMID- 1419476 TI - Ondansetron as an antiemetic. PMID- 1419477 TI - Avoiding nitrate tolerance. PMID- 1419479 TI - Insulin receptor gene mutation: a molecular genetical and functional analysis. PMID- 1419478 TI - Recent evidence for common signalling mechanisms among immunoreceptors that recognize foreign antigens. PMID- 1419480 TI - Alterations in G-protein expression, Gi function and stimulatory receptor mediated regulation of adipocyte adenylyl cyclase in a model of insulin-resistant diabetes with obesity. AB - The stimulatory effect of Mn2+ (1.5-fold), forskolin (1.6-fold) and low (1 microM) concentrations of GTP (1.9-fold) on the adenylyl cyclase of adipocyte membranes from obese, diabetic CBA/Ca mice was markedly enhanced compared to that seen using membranes prepared from their lean littermates. In contrast, receptor mediated stimulation, achieved with either isoprenaline or secretin was reduced and that by glucagon abolished in membranes from diabetic animals. The levels of expression of alpha-subunits of Gi-1, Gi-2 and Gi-3 were reduced to some 49, 76 and 54%, respectively, in membranes from diabetic animals compared with those from normal animals. Levels of G-protein beta-subunits and Gs alpha-subunits were similar. Receptor-mediated inhibition of adenylate activity elicited by either nicotinic acid or prostaglandin E1 (PGE1) was of a similar magnitude in membranes from normal and diabetic animals but the inhibitory action of N6-(L-2 phenylisopropyl)adenosine (PIA) was greater in membranes from diabetic animals by about 30%. Gi function was similarly evident in membranes from both lean and diabetic animals, as assessed using low concentrations of guanylyl 5' imidodiphosphate to inhibit forskolin-stimulated adenylyl cyclase activity. However, assessing Gi function using GTP showed marked dissimilarities in that the elevated GTP concentrations expected to occur physiologically were incapable of reversing the stimulation achieved at low concentrations of GTP in membranes from diabetic but not normal animals. The adipocytes of CBA/Ca mice, as do other animal models of insulin resistance, show lesions in adenylyl cyclase regulation, Gi function and G-protein expression. PMID- 1419481 TI - Involvement of pertussis toxin-sensitive and -insensitive GTP-binding proteins in luteinizing hormone exocytosis distal to second messenger generation. AB - Inhibition of luteinizing hormone (LH) exocytosis by guanosine 5'-[gamma thio]triphosphate (GTP gamma S) in permeabilized pituitary cells has indicated the involvement of one or more GTP-binding proteins in the exocytotic mechanism distal to second messenger generation. We now report that two inhibitory sites of action of GTP gamma S can be distinguished by their dependence on GTP gamma S concentration and their sensitivity to pertussis toxin. Ca(2+)-stimulated exocytosis was half-maximally inhibited by 6.8 microM GTP gamma S, a six-fold higher concentration than that required for inhibition of exocytosis stimulated by phorbol ester plus cAMP. In addition, GTP gamma S inhibition of Ca(2+) stimulated exocytosis was insensitive to pertussis toxin, in contrast to the inhibition of exocytosis stimulated by phorbol ester plus cAMP, which was abolished by pretreatment with pertussis toxin. These results indicate that at least two stimulus-specific GTP-binding proteins are involved in regulating LH exocytosis distal to second messenger generation. PMID- 1419482 TI - Protein kinase C initially inhibits the induction of meiotic cell division in Xenopus oocytes. AB - We have used one activator and two inhibitors of protein kinase C (PKC) to examine the role of this enzyme in the induction of meiotic cell division. At 1 U/ml, phosphatidylcholine-specific phospholipase C increases DAG, alters intracellular pH and inhibits the induction of meiosis by insulin or progesterone. However, when added about 1.6 h after progesterone, the enzyme speeds the induction of cell division. Microinjection of inhibitor peptide (19 36) of PKC has little effect on progesterone action but stimulates the induction of meiosis by insulin. When the inhibitor peptide is injected about 2h after insulin addition, the peptide inhibits. A second PKC inhibitor, staurosporine, decreases PKC-dependent intracellular pH and in vitro oocyte PKC activity. At similar concentrations, staurosporine stimulates insulin or progesterone action, but, when added after about 2 h, the drug inhibits induction by insulin. We conclude that PKC is initially inhibitory to the induction of meiotic cell division but then may become synergistic. PMID- 1419483 TI - Two protein kinase C activators, bryostatin-1 and phorbol-12-myristate-13 acetate, have different effects on haemopoietic cell proliferation and differentiation. AB - Primary B lymphocytes can be induced to proliferate and certain haemopoietic cell lines such as HL60 and U937 can be induced to differentiate by the addition of phorbol esters, which have been shown to activate protein kinase C. Several non phorbol esters, such as the bryostatins, have also been shown to bind to and activate protein kinase C. Although bryostatin-1 and 12-O-tetradecanoylphorbol-13 acetate (TPA) compete for and activate protein kinase C to the same degree and with similar kinetics and also induce similar levels of expression of the CD23 cell-surface antigen, bryostatin-1 is a weak mitogen for B lymphocytes and fails to induce the differentiation of both HL60 and U937 cells. Such an outcome suggests that these two activators have different binding properties for the enzyme that have a physiological consequence which may be useful for analysing the role that protein kinase C plays in both differentiation and proliferation. Analysis of competition assays between bryostatin-1 and TPA leads us to put forward a model where protein kinase C is required to be constantly reactivated and recycled during proliferation and differentiation which can be accomplished by TPA but not by bryostatin, although we cannot exclude the differential activation of some of the sub-species of the kinase by the two agonists. PMID- 1419484 TI - Microinjection of the alpha-subunit of the G protein Go2, but not Go1, reduces a voltage-sensitive calcium current. AB - Calcium currents can be modulated by receptor activation of the GTP-binding protein G(o). We have determined whether the two forms of G(o), Go1 and Go2, differentially regulate calcium current magnitude. Using identified neurons of the pond snail Helisoma, we demonstrate that a high-voltage-activated (HVA) calcium current is reduced by addition of the neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide) and that this inhibition is mediated by a pertussis toxin (PTX) sensitive G protein pathway. Using this calcium current as an assay for G protein activity, we microinjected GTP gamma S-activated alpha-subunits of G proteins into neuronal somata. We demonstrate that the calcium current is differentially regulated by the two forms of alpha o. Microinjection of alpha o2*, but not alpha o1*, reduces calcium current magnitude. PMID- 1419485 TI - Autophosphorylation of Mucor rouxii cAMP-dependent protein kinase and its role in holoenzyme activation. AB - Two phosphoproteins of 53,000 and 63,000 mol. wt detected in partially purified preparations of Mucor rouxii cAMP-dependent protein kinase submitted to phosphorylation conditions with [gamma-32P]ATP are demonstrated to be the result of the autophosphorylation of its regulatory subunit, according to the following criteria: (1) linearity of phosphate incorporation with enzyme sample; (2) independence of phosphate incorporation on temperature; (3) correlation of the phosphoproteins with enzymatic activity in a DEAE-Sepharose chromatography; (4) specific elution of the phosphorylated proteins from cAMP-agarose; (5) phosphorylation of the purified regulatory subunit. Antibodies specific against Mucor regulatory subunit detected an intact subunit of 72,000 mol. wt in crude extracts. Autophosphorylation of the fungal protein kinase A promotes activation of the holoenzyme by cAMP since: (1) under conditions of partial activation, increase of activity is observed when using the phosphoform of the enzyme; (2) release of free catalytic subunit from cAMP-agarose is enhanced when the holoenzyme is previously phosphorylated. PMID- 1419486 TI - Signalling across the endoplasmic reticulum membrane: potential mechanisms. AB - The endoplasmic reticulum (ER) is a membrane-bound organelle responsible for the synthesis, assembly and post-translational modification of proteins destined for the lysosomes, Golgi and for secretion. The processes which occur in the lumen of the ER are vital to the correct functioning of the cell, and mechanisms must exist to enable the cell to monitor events within the lumen of the ER. How the cell is able to do this is not known, but it would apparently require the passage of signals from the lumen of the ER to the cytosol, from where signals can be sent to, for example, the nucleus to effect changes in transcription. Here, it is suggested that the membrane of the ER may contain the components (i.e. receptors, kinases, etc.) required for transmembrane signalling in much the same way as the plasma membrane does. This hypothesis will be discussed in relation to known ER proteins which might act as signalling proteins. PMID- 1419487 TI - Granulocyte-macrophage colony-stimulating factor primes phospholipase D activity in human neutrophils in vitro: role of calcium, G-proteins and tyrosine kinases. AB - The addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to human peripheral blood neutrophils primes phospholipase D (PLD) to subsequent stimulation by N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA). The present investigation was directed at the elucidation of the pathway(s) involved in the regulation of the activity of PLD in untreated as well as in GM-CSF-primed neutrophils. Pretreatment with pertussis toxin (PT) totally inhibited fMLP-induced activation of PLD in control or GM-CSF treated cells. PT did not affect the activation of PLD by PMA but inhibited the priming effect of GM-CSF. Activation of PLD by fMLP was dose-dependently inhibited by erbstatin, an inhibitor of tyrosine kinases. Furthermore, pre incubation with GM-CSF accelerated the tyrosine phosphorylation response to fMLP (as analysed by protein immunoblot with antiphosphotyrosine antibodies). In PMA stimulated neutrophils, erbstatin antagonized the priming effect of GM-CSF on PLD without affecting the direct effects of the phorbol ester. Buffering cytoplasmic calcium with the chelator BAPTA inhibited fMLP-induced activation of PLD as monitored by the formation of phosphatidylethanol. The stimulation of PLD by PMA was partially attenuated in BAPTA-loaded cells while the priming effect of GM-CSF was abolished. Thus, priming of human neutrophil PLD by GM-CSF may be mediated by G-proteins, by increases in the levels of cytosolic free calcium, and by stimulation of protein kinase C and/or tyrosine kinase(s). PMID- 1419488 TI - Differential up-regulation of specific and azurophilic granule membrane markers in electropermeabilized neutrophils. AB - We have developed an alternative method to study the degranulation in electropermeabilized human neutrophils by measuring the up-regulation of the specific membrane markers CD63 (residing in the azurophilic granules of resting neutrophils) and CD67 (present in specific granules). The expression of these marker proteins was measured by the binding of specific antibodies to paraformaldehyde-fixed cells and subsequent flow cytometry. We first investigated whether the changes in CD63 and CD67 expression after stimulation of intact cells were comparable with earlier measurements of neutrophil degranulation, in which the release of soluble marker proteins was measured. These experiments indicated that this new method compares favourably with earlier studies, both with respect to kinetics and stimulus dependency. Subsequently, we applied this method (which does not include centrifugation of the cells) to study degranulation in electropermeabilized neutrophils. In permeabilized neutrophils, a clear up regulation of the specific granule marker CD67 was observed upon incubation with a free Ca2+ concentration of 1 microM, a value of the cytosolic free Ca2+ concentration occurring in formylmethionyl-leucyl-phenylalanine (FMLP)-activated neutrophils. The azurophilic granule marker CD63 required GTP-gamma-S besides 1 microM Ca2+ for a significant up-regulation. Hence, our study indicates a different requirement for intracellular signals of the two main types of granules in human neutrophils. PMID- 1419490 TI - Adenosine inhibits divalent cation influx across human neutrophil plasma membrane via surface adenosine A2 receptors. AB - Adenosine and its analogues inhibited increases in divalent cation influx stimulated by platelet-activating factor (PAF) and formyl-methionyl-leucyl phenylalanine (FMLP) in a dose-dependent fashion. This effect was antagonized by theophylline, an adenosine receptor antagonist. When extracellular adenosine was removed by adenosine deaminase, the effect of adenosine was completely abolished. Two adenosine analogues with different affinities for adenosine receptor subtypes, 5'-N-ethylcarboxamideadenosine (NECA) and L-N6-phenylisopropyladenosine (PIA), also inhibited divalent cation influx, NECA being more potent than PIA. These results suggest that adenosine and its analogues inhibit divalent cation influx across neutrophil plasma membranes via surface adenosine A2 receptors. Adenosine had little effect on the initial peaks of intracellular free calcium rises induced by chemoattractants, but it inhibited the subsequent rise in free calcium. Since calcium influx through the divalent cation channels or neutrophil plasma membranes is responsible for maintaining free calcium concentration following the initial peaks, we suggest that adenosine modulates neutrophil function by interfering with this calcium influx. PMID- 1419489 TI - Evidence on the role of three calcium pools in Ca-ionophore A23187-stimulated rat blood platelet aggregation. AB - The effect of Ca-ionophore A23187 on activation of rat blood platelets was investigated to elucidate the involvement of extracellular and intracellular Ca2+ ions. Platelet aggregation induced by 10 concentrations of the stimulus was studied in Ca-free medium as well as in the presence of EGTA and/or calcium. In Ca-free medium, A23187 induced platelet aggregation in a dose-dependent way; the mean effective concentration was 1.43 +/- 0.08 mumol/l. The stimulatory effect of ionophore was potentiated by addition of 0.01 and 0.1 mM calcium and inhibited when the calcium concentration was increased to 1 mmol/l. In the presence of EGTA, A23187-stimulated aggregation of isolated rat platelets was recorded only at a 10-times higher ionophore concentration and was then reduced to 30% in comparison with aggregation in Ca-free medium. The inhibitory effect of 1 mM EGTA was abolished by addition of 2 mM calcium. We suggest the participation of at least three calcium pools in the stimulation of rat platelets by A23187, i.e. the extracellular pool, the membrane-associated pool and the pool displacing calcium intracellularly. PMID- 1419491 TI - Modulation of human growth hormone binding to somatogenic and lactogenic receptors by monoclonal antibodies to human growth hormone. AB - The relationship between the structure of human growth hormone (hGH) and the hormone-receptor interaction was investigated by studying the effects of specific monoclonal antibodies (MAbs) to hGH on the binding of [125I]hGH to rabbit liver and mouse liver microsomes. Receptor binding assays were carried out using a constant dose (1 ng) of [125I]hGH and varying concentrations of MAbs. The assay was carried out in the presence of either excess ovine prolactin for the measurement of somatogenic (SOM) binding sites, or excess bovine growth hormone for the determination of lactogenic (LAC) binding sites. Anti-hGH MAbs were found to have a whole spectrum of effects on hGH binding, including inhibitory, non effect and enhancing activities. Enhancement of the binding of [125I]hGH to both SOM and LAC receptors was observed in liver membranes of rabbit or mouse. The observed amplified signal of [125I]hGH binding to various receptors in the presence of MAb no. 8 may be due to conformational changes which occur following MAb binding to hGH. On the other hand, most of the other MAbs caused inhibition of [125I]hGH binding. A negative correlation exists between the cross-reaction of various MAbs with the N-terminus truncated forms of hGH (Met14-hGH or Met8Leu hGH) and their respective KD/IC50 values enabled the evaluation of the crucial role of the N-terminus region in hGH binding to both LAC and SOM receptors. MAb nos 1 and 19, which are directed towards acid residues 95-134 and the C-terminus, inhibited SOM binding more potently than LAC binding. Thus, it seems that these mid-molecule and C-terminus regions are also important in hGH binding, and that they play a role in the partial overlap of SOM and LAC binding. PMID- 1419493 TI - Low molecular mass phosphoproteins from the frog rod outer segments form a complex with 48 kDa protein. AB - Upon separation of cAMP-dependent low molecular mass phosphoproteins [Components I and II; Polans et al. (1979) J. gen. Physiol. 74, 595-613] from the frog rod outer segments by gel-chromatography, isoelectric focusing, non-denaturating electrophoresis and ion-exchange chromatography, they behave like subunits of the oligomeric complex. Apparent molecular mass of the complex determined by gel chromatography is 52-57 kDa and by non-denaturating gradient electrophoresis is 62-66 kDa. The isoelectric point of the complex is 5.5. The elution profile of Components I and II upon gel-chromatography and ion-exchange chromatography coincides with that of major rod outer segment 48 kDa protein. The isoelectric point for them also coincides with the isoelectric point of 48 kDa protein. The amount of low molecular mass phosphoproteins is sealed rods is equal to one molecule per 60 rhodopsin molecules and coincides with that of a 48 kDa protein. It is suggested that in solution Components I and II form an oligomeric complex with 48 kDa protein. PMID- 1419494 TI - Systemic lupus erythematosus and Sjogren's syndrome. PMID- 1419492 TI - Immunological identification of protein kinase C-alpha and protein kinase C-delta in cultured rat mesangial cells: differential sensitivity of the two isoforms towards the protein kinase inhibitor H7. AB - Rat mesangial cells contain both calcium-dependent protein kinase C (PKC) activity, which phosphorylates histone H1 and endogenous proteins, and calcium independent, phospholipid-dependent PKC activity, which phosphorylates only endogenous proteins. The calcium-dependent PKC was identified as PKC alpha by immunoblot analysis and hydroxyapatite chromatography (HPLC). The calcium insensitive, phospholipid-dependent isoform was identified as PKC delta using similar techniques. The inhibition of these two PKC isoforms by the protein kinase inhibitor H7 [1-(iso-quinolinyl sulphonyl)-2-methyl piperazine] was examined using both histone H1 and endogenous proteins as substrates. Phosphorylations catalyzed by the calcium-dependent PKC isoform alpha were almost 90% inhibited when histone H1 was used, and only 55% when endogenous proteins were the substrate. In contrast, the phosphorylation of endogenous proteins catalysed by the calcium-insensitive, phospholipid-dependent PKC delta was not significantly affected by the inhibitor. PMID- 1419495 TI - Murine models of autoimmunity: T-cell and B-cell defects. AB - The lpr gene has been identified as a defect in the Fas gene, which encodes a lymphocyte surface protein associated with apoptosis and shares homology with the tumor necrosis factor-alpha receptor. This finding is important as it may quickly lead to identification of the gld gene product, which is thought to be a ligand for Fas. Also, it clearly identifies autoimmune disease as originating from a defect in the ability to induce cell death in lymphocytes. The major challenge in the future will be to directly demonstrate the relationship of abnormal apoptosis pathways to the development of autoimmunity and, in the case of lpr and gld mice, to lymphadenopathy, and to eventually determine if this is a fundamental defect at the root of all autoimmune diseases in both mice and humans. PMID- 1419496 TI - Murine models of autoimmune disease. AB - Animal models of autoimmunity are used to identify important immunologic factors and pathways involved in the different autoimmune diseases. Identification of the role of cytokines and development of new disease models have led to new possibilities for treatment. PMID- 1419497 TI - Autoantibodies and their idiotypes. AB - Antinuclear antibodies occur prominently in systemic lupus erythematosus and serve as markers of underlying pathogenetic disturbances. Although these antibodies display features indicative of genetic control and in vivo selection by self-antigen, other mechanisms shaping the B-cell repertoire may influence their production. Provocative new animal models provide systems for analyzing the cellular and genetic disturbances promoting these responses, as well as the role of pathogenic specificities in inducing tissue injury. PMID- 1419498 TI - The molecular genetics of systemic lupus erythematosus and Sjogren's syndrome. AB - Refinements in molecular genetic technology as well as in the organization of the major histocompatibility complex and the genes contained therein continue to lead the way to elucidation of the immunogenetics of systemic lupus erythematosus and Sjogren's syndrome. In this article, recent advances in these areas are reviewed, and major histocompatibility complex associations with systemic lupus erythematosus and Sjogren's syndrome will be explored with particular emphasis on autoantibody subsets of these diseases. Data thus far support the hypothesis that systemic lupus erythematosus and Sjogren's syndrome are clinically and serologically heterogeneous disorders of major histocompatibility complex class II allele-associated autoantibody subsets, to which other major histocompatibility complex genes (C4 null alleles) and non-major histocompatibility complex genes (such as T-cell receptor genes) may contribute in susceptibility. PMID- 1419500 TI - Antiphospholipid antibody and antiphospholipid antibody syndrome. AB - Over the past year, many reports have been published on a variety of clinical manifestations related to antiphospholipid antibodies. The low prevalence of anticardiolipin antibodies with the rare occurrence of thrombosis and a low rate of fetal loss in studies in Malaysia and China showed a potential role for local factors. A study of cross-reactive idiotype of the anticardiolipin antibody suggested that anticardiolipin antibodies are derived from a set of natural autoreactive clones. Regarding the pathogenic role of the antiphospholipid antibody, evidence has been presented that the epitopes formed between cardiolipin and beta 2 glycoprotein I are the targets of the antiphospholipid antibody. Complement activation, abnormalities of natural anticoagulants such as protein S deficiency, and genetic association with DR4, DR7, and DRw53 have also been studied. PMID- 1419499 TI - New developments in Sjogren's syndrome. AB - Sjogren's syndrome is an autoimmune exocrinopathy with characteristics of both organ-specific and generalized autoimmune disease. The main features are keratoconjunctivitis sicca and xerostomia, but patients may also show signs of extraglandular involvement. Sjogren's syndrome can occur in the absence (primary Sjogren's syndrome) or in the presence of other connective tissue disease (secondary Sjogren's syndrome). Sjogren's syndrome has often been considered a link in the spectrum between autoimmune disease and lymphoproliferative disorders. The cause of Sjogren's syndrome is still unknown, although the role of viruses in the pathogenesis is disputed. There is still no consensus about the diagnostic criteria, due to lack of specificity and sensitivity of the diagnostic procedures performed thus far. Recent studies using immunohistochemical and molecular biologic techniques highly suggest that disturbances in the target organs, such as salivary glands, are the consequence of local processes, rather than the reflection of systemic alterations. This underlines the importance of implementing these techniques for diagnostic purposes. Based on increasing understanding of the pathogenetic processes, new therapeutic possibilities will come into the picture. Over the past few years, interesting studies have contributed to our knowledge of the disease. PMID- 1419501 TI - Clinical manifestations of systemic lupus erythematosus, measures of disease activity, and long-term complications. AB - Studies of renal involvement in systemic lupus erythematosus continue to dominate the clinical literature. Reports of the prognostic significance of both clinical and histologic parameters at the time of renal biopsy are discussed. The potential impact of anticardiolipin antibodies on the development of renal insufficiency is described. The outcome of renal transplantation in patients with systemic lupus erythematosus is assessed in a study concerned with both allograft survival and recurrence of active nephritis in the transplanted kidney. The incidence and prognosis of various features of neuropsychiatric systemic lupus erythematosus are discussed, while the search for an accurate indicator of lupus involvement of the central nervous system continues. Magnetic resonance imaging and single-photon-emission computed tomography are considered. Abnormalities of pulmonary gas exchange are featured in several reports. Features of the antiphospholipid antibody syndrome are presented, stressing predisposition to thrombosis. The definition and characteristics of systemic lupus erythematosus disease flares is discussed, in relation to several recently developed disease activity indexes. The attempt to distinguish systemic lupus erythematosus activity from infection and preeclampsia is also considered. Finally, the association of systemic lupus erythematosus with the development of cancer is discussed. PMID- 1419502 TI - Prognosis of systemic lupus erythematosus and factors that affect it. AB - The prognosis of systemic lupus erythematosus has improved over the past four decades. We now have data for 15-year survival, which has also improved. Several factors may be associated with improved survival, including earlier diagnosis, better treatment, and improved medical therapy. Specific organ damage continues to be an issue, primarily with regard to kidney disease and to neurocognitive impairment and lung involvement. Infection and vascular disease emerge as important factors. With improved survival, other outcome measures, including specific organ function and health status, need to be considered. PMID- 1419503 TI - Role of drugs and environmental agents in lupus syndromes. AB - It is increasingly accepted that a broad range of drugs and environmental factors can give rise to lupus syndromes and other types of connective tissue disease syndromes. This chapter reviews the drugs and environmental agents reported during this past year. Considerable research efforts are now focused on understanding the possible mechanisms, particular specificities of the antibody responses, new patterns of antibody responses, and biochemical pathways. These potentially important contributors to the expression of disease are reviewed. PMID- 1419505 TI - Pediatric and heritable disorders. PMID- 1419504 TI - Treatment of systemic lupus erythematosus. AB - The past year continued to see both major studies and interesting case reports slowly add suggestions, if not absolute knowledge, concerning the treatment of systemic lupus erythematosus. The Lupus Nephritis Collaborative Study Group published two papers, one of which concerned the lack of efficacy of plasmapheresis in treating severe lupus nephritis. A related paper documented the utility of initial serum creatinine in predicting renal failure in patients enrolled in both arms of the plasmapheresis study. Patients in the study received high-dose oral prednisone and low-dose oral cyclophosphamide. Whether this approach is superior to pulse intravenous cyclophosphamide is yet to be determined. Two other approaches to treatment were also reported: anti-CD4, based on success in case reports, merits further study; the modified androgen, 19 nortestosterone, was unfortunately not effective. Other case reports provide additional evidence for specific treatments in certain situations, such as the use of tetracycline pleurodesis for recurrent pleural effusions. Finally, reports of new side effects for old medicines and new ones are a reminder that the treatment can be part of the problem when a lupus patient develops complications. PMID- 1419506 TI - Juvenile rheumatoid arthritis, juvenile chronic arthritis, and juvenile spondyloarthropathies. AB - Immunogenetics are supporting the marked heterogeneity of chronic arthritis in children. Thus DRw13-DRw18 and DQw6-DQw18 were associated with persistent pauciarticular disease in children with an early onset of disease. Several studies have shown DPw2 as an additional susceptibility factor in this subgroup. Standardization of diagnostic criteria for juvenile onset spondyloarthropathy and psoriatic arthritis is necessary; various studies are in progress, and although HLA-B27 provides the common marker, this may only apply to a small group of juvenile psoriatics who have spondyloarthropathy. In the management of juvenile rheumatoid arthritis, methotrexate in moderate doses has been shown to be superior to lower doses of methotrexate and placebo in controlling polyarthritis. Methotrexate may be of particular value in treating the polyarthritis that follows a pauciarticular onset. The possible value of sulfasalazine in a B27 group with persistent polyarthritis has been suggested. Highlights of corticosteroid therapy were intra-articular injections, particularly in pauciarticular disease, the suggestion that deflazacort has a calcium sparing effect, and the possible role of intravenous methylprednisone in the management of severe disease. PMID- 1419507 TI - Rheumatic diseases. PMID- 1419508 TI - Rheumatic fever and disorders of the musculoskeletal system. AB - New information provided on the pathogenesis and management of rheumatic fever is of current interest. Invasive disease by group A streptococci has been shown to be due to production of toxin A. The natural history and immunopathologic basis for chronic Lyme arthritis are reported. Attention is drawn to pyomyositis and clinical presentation of chronic fatigue syndrome in children. Patients with Sweet's syndrome often have antineutrophil cytoplasmic autoantibodies. Biopsy specimens of panniculitis should be taken to aid treatment. Long-term outcome in chronic osteomyelitis is favorable; recommendations on the rational use of imaging have been reported. PMID- 1419509 TI - Musculoskeletal signs of metabolic and systemic diseases in childhood. AB - Many metabolic and systemic disorders affect the musculoskeletal system in growing children. This review surveys some of the recent literature in several diverse areas, including new radiologic methods to determine bone mineralization and their use in children with juvenile arthritis and other systemic diseases, bone disorders in childhood, and the association of endocrinopathies and musculoskeletal symptoms. PMID- 1419510 TI - Heritable disorders of connective tissue and disability and chronic disease in childhood. AB - The heritable disorders of connective tissue encompass a broad range of diseases, many of which occur in childhood and present to the pediatric rheumatologist's attention. The underlying theme of these disorders is fragility of connective tissue components such as bone, cartilage, and blood vessels. Over the past few years, investigations of patients with the major forms of heritable disorders of connective tissue, osteogenesis imperfecta, Marfan syndrome, and Ehlers-Danlos syndrome have revealed genetic mutations of collagen genes as the cause of the diseases. Review of the newest genetic information in these three disorders is presented. The rheumatic disorders of childhood present a paradigm for the effects of chronic disease on children and families. New work, discussed in this review, continues to suggest changes in psychosocial adaptation in children with chronic rheumatic diseases and their families, but these data are conflicting. The development of arthritis impact measures may help workers in pediatric rheumatology care to have a broader and more in-depth understanding of the effect of this chronic disease on functioning, psychosocial development, and family and peer interactions. PMID- 1419511 TI - Musculoskeletal tumors in childhood. AB - As treatment strategies improve, the ability to cure children with musculoskeletal tumors is growing. The stage of a given malignancy, representing the degree of spread of the tumor to its local surroundings or distant sites, is the best predictor of long-term survival. Unfortunately, the insidious nature of the presentation of these tumors leads to their late recognition in advanced stages. This review will present scenarios suggesting the need for consideration of malignancy in the differential diagnosis of clinical problems related to the musculoskeletal system. Pitfalls in diagnosis and therapeutic approaches will also be discussed. PMID- 1419513 TI - Systemic lupus erythematosus and Sjogren's syndrome. PMID- 1419514 TI - Pediatric and heritable disorders. PMID- 1419512 TI - Pain of musculoskeletal origin in children. AB - Pain in infants and children may be manifest by deformity, altered function, or discomfort. These manifestations are highly age related. Pseudoparalysis may be the only manifestation of septic arthritis of the hip in the neonate; a limp is often the presenting complaint in Perthes' disease, and scoliosis may be the primary manifestation of a herniated disc in an adolescent. New imaging methods aid in diagnosis. Ultrasound is helpful in assessing joint effusions; bone scans localize the cause of a limp; and magnetic resonance imaging shows spinal cord and root lesions. The traditional methods of assessment have not been replaced. History and physical examination are most essential to provide a rational basis on which to select the appropriate imaging study. PMID- 1419515 TI - [Surgery of laparocele]. PMID- 1419516 TI - [Surgical treatment of post-thyroidectomy laryngeal paralysis]. AB - A not infrequent complication of thyroid surgery is laryngeal nerve palsy with transitory or permanent deficiency of cordal motility. A very frequent cause of this condition is total thyroidectomy. Peripheral mono-or bilateral palsy in these cases may either occur, in adduction or abduction, and be complete or not complete. Therefore, different strategies in order to restore respiratory and phonatory functions are required. The Authors describe the main otorhinolaryngologic procedures used for the surgical treatment of laryngeal palsy, particularly for bilateral adducted ones. Their 10-year experience is also reported. PMID- 1419517 TI - [Therapeutic trends in adrenal incidentaloma]. AB - The term incidentally discovered adrenal mass or incidentaloma includes several tumors, mainly benign, involving the adrenal space. From 1983 to 1990, at the 1st Surgical Department of the Careggi Hospital of Florence, 10 patients (8 females and 2 males), with age ranging from 31 to 66 years, were found to have an incidentaloma. The size of the mass ranged from 2 to 10 cms; the left side was interested in 2 cases and the right one in 8 cases. The first diagnostic approach was abdominal ultrasound scanning in 8 out of 10 patients, whereas computerized tomography was the first used in the remaining 2 patients. Overall, all patients underwent CT scanning, while abdominal ultrasound scanning was performed in 9, urography in 2, and MNR in 1. Fine needle aspiration was performed in one case of adrenal cyst both for diagnostic and therapeutic purposes. The Authors suggest a therapeutic-diagnostic program in which cytology, obtained through fine needle aspiration, may have a prominent role in reducing the need for surgical interventions, as it recently happened for thyroid disorders. Although technically more complex compared to thyroid fine needle aspiration, adrenal ultrasound-guided FNA may bring to a better classification of the different adrenal disorders reducing at the same time the need for surgery, which at present has a prevalent diagnostic intent. PMID- 1419518 TI - [Carcinoma of the splenic flexure]. AB - The Authors report their experience in the management of 25 cancers of the splenic flexure corresponding to 4.8% of large bowel cancers overall observed. Twelve patients underwent elective surgery consisting in a left hemicolectomy, which in 1 of the 12 cases required an associated distal splenopancreatectomy. Operative mortality was null, whereas morbidity involved 1 case of anastomotic dehiscence. Thirteen patients presenting with complete obstruction underwent emergency surgery: a two-stage resection with primary colostomy was performed in 5 cases, a sub-total colectomy with one-stage ileo-rectal anastomosis or ileo sigmoid anastomosis was performed in 8 cases. In this last group of 8 patients mortality rate was 12.5% (1 pt.) and diarrhoea was the most important sequela. On this regard the Authors point out the opportunity to perform an ileo sigmoidostomy, which reduces the incidence of such complication. PMID- 1419519 TI - [Cystic tumors of the pancreas: a case of cystadenocarcinoma of the pancreatic head]. AB - Cystic tumors of the pancreas are important, although rare, lesions representing nearly 1% of all neoplasms and 10-15% of pancreatic cysts. The Authors compare clinical data of the case observed with those reported in literature. The described case confirms the peculiar characteristics of pancreatic mucinous cystoadenomas: slow growth, not specific symptoms, poor trend to give local or distant metastases, difficult preoperative differential diagnosis and satisfying oncological resection. Taking into account these parameters and the potential malignant evolution of such tumors, the Authors underline the importance of a radical surgical therapy. PMID- 1419520 TI - [Emergency endoscopic sphincterotomy in acute lithiasic cholangitis]. AB - Emergency endoscopic sphincterotomy in acute cholangitis for bile duct stones should be the first choice treatment in patients with and without gallbladder. In fact, emergency surgery carries higher mortality and morbidity rates. Urgent biliary drainage, easily and quickly obtainable by endoscopy is the major goal. Bile duct stone clearance can be attempted subsequently, when the patient general conditions are stable. Elective open surgery can be performed thereafter, if indicated, with less risk. This experience is clearly shown by many surgical and endoscopic, mainly retrospective, studies. PMID- 1419521 TI - [New trends in the diagnosis of Crohn's disease]. AB - The Authors in reviewing the diagnostic techniques commonly used in Crohn's disease, focus their attention on Indium-111 scanning. The method seems useful, not only to point out the complications of the disease (stenosis, abscess, fistula) but especially for the follow up of patients after surgery with early diagnosis of a possible relapse. PMID- 1419522 TI - [Revascularization of distal arteries of the leg: critical considerations on more than 2000 cases reported in the literature]. AB - The Authors review the results of more than 2000 cases of lower extremity revascularization, treated from 1969 to 1991 and reported in the literature. They evaluate indications, contraindications and results at 12 and 24 months from operation performed with saphenous vein "in situ" and reversed. Finally they stress the greater reliability of by-passes performed with "in situ" saphenous vein graft. PMID- 1419523 TI - Existing and emerging foodborne diseases. AB - Foodborne diseases, i.e. illnesses due to contaminated food, are one of the most widespread problems of the contemporary world. They are toxic or infectious by nature and are caused by agents which enter the body through the ingestion of contaminated food or water. These agents can be chemical like pesticide residues and toxic metals or biological like pathogenic microorganisms. Foods contaminated by biological agents are, however, the major cause of foodborne disease. Data recorded in different countries show that the incidence of some of these diseases has increased dramatically over the past few years, but because of under reporting the data are of limited value and cannot be compared between countries. In most countries, individual cases of illness are usually not reported. A sentinel surveillance system, started as a pilot study in the Netherlands, was shown to be feasible for the registration of some foodborne infections. Based on this study, it can be estimated that each year Salmonella and Campylobacter cause respectively about 12,000 and 25,000 cases of acute enteritis per million. Case control studies clearly implicate poultry products as an important source of acute enteritis. New developments in food production and changing trends in food consumption lead to the emergence of new hazards. Additionally, because the population is aging and there has been an increase in the number of individuals with underlying diseases, the state of public health is deteriorating. Campylobacter, Salmonella enteritidis and enterohemorrhagic Escherichia coli are examples of microorganisms that have the opportunity to increase as a consequence of intensive husbandry. Listeria monocytogenes is an example of an organism that causes disease in immunosuppressed individuals. PMID- 1419524 TI - The economic impact of poultry-borne salmonellosis: how much should be spent on prophylaxis? AB - Foodborne salmonellosis constitutes a major health problem in many countries. Moreover, the costs associated with salmonellosis could be considerable. There are thus strong arguments for preventive efforts. Ambitious, often government sponsored, programmes aimed at preventing and controlling salmonellosis in for instance, poultry production represent one alternative to lower salmonellosis related illness and economic costs. On the other hand, such comprehensive programmes are rather resource-demanding. From the economic point of view the key problem is to find the optimal level for prophylactic measures. The purpose of this study is to compare two different approaches to preventing poultry-borne salmonellosis among humans. We identify and compare the economic costs of illness due to poultry-borne salmonellosis and the costs of salmonella control in England and Wales and Sweden, respectively. An alternative option is then introduced: the concept of competitive exclusion (CE). Our results show that the cost of illness constitutes the major part of the total cost in England and Wales, whereas in Sweden, the control cost amounts to 95% of the total cost. By using the CE concept, the cost of illness due to poultry-borne salmonellosis in England and Wales could be reduced by at least GB pound 12.6 million. These advantages apply to individuals, producers, and to society, and we thus conclude that the CE concept is a very cost-effective way of using scarce resources. PMID- 1419525 TI - Control of Salmonella in poultry in Great Britain. PMID- 1419526 TI - A voluntary Salmonella control programme for the broiler industry, implemented by the Danish Poultry Council. AB - In the light of data and experience gained over the last two decades, initiatives made to combat and control Salmonella in the Danish broiler industry are described and the results obtained so far are discussed. The main elements include evaluation of the establishments, procedures and processes used, including bacteriological assessment, advice and guidance, routine bacteriological monitoring, and also research. Results obtained are used in the control of breeding stock, parent stock, hatcheries, broiler farms, slaughterhouses, feedmills and transport systems. PMID- 1419527 TI - Problems of Salmonella sampling. AB - Modern husbandry practices, regional concentration of the industry, high stocking densities, uniform age-distribution of birds and continuous feeding promote the spread of poultry diseases. Moreover, the immature state of the intestinal microflora or disturbance of the developing flora by antibiotics increases susceptibility of chicks to salmonellas. If an estimate of the number of salmonella-positive birds in a flock is needed, then the required number of samples can be assessed by using the binomial distribution function. Whenever a qualitative result is sufficient, the samples can be pooled or the flock litter can be sampled using an 'overshoe method', which is a novel, low-cost and rapid technique. An optimal pooling factor can be assessed at low prevalence levels (less than 10%). Serological methods will only detect the presence of antibodies to invasive strains of Salmonella. The sampling interval depends on the strategy of the Salmonella Control Programme. Breeder flocks should be sampled more frequently than meat flocks and laying flocks. The new salmonella standard, ISO 6579-1990, is applicable in the poultry industry. When bacterial numbers are likely to be low, or the organisms in a stressed condition, a pre-enrichment step should be included. In the case of faecal samples, however, pre-enrichment should be omitted. A whole carcass rinsing and massaging method is preferred for the examination of finished carcasses. PMID- 1419528 TI - The competitive exclusion concept: development and future. AB - The origin of the competitive exclusion (CE) concept in controlling a Salmonella infantis outbreak in poultry in 1971 and the subsequent development of a commercial treatment product are described. The possible role of CE in salmonella control, current status of the concept and theories relating to the bacteria involved and mechanisms of protection are reviewed. Some observations are made on the need for methodological development and possibilities for extending the scope of CE to other pathogens and types of domestic animal. PMID- 1419529 TI - Competitive exclusion in the young bird: challenge models, administration and reciprocal protection. AB - The competitive exclusion (CE) concept has been tested against both non-invasive and invasive salmonella serotypes. Studies with different challenge models indicate that CE treatment is likely to protect the young bird against all serotypes that are capable of intestinal colonization. Spray or 'droplet' application of the CE-treatment material was compared with administration in the first drinking water. Both methods gave a similar degree of protection against Salmonella infantis. A study was made to compare protection of newly hatched chicks and turkey poults by the one commercial CE product Broilact, and two similar preparations involving intestinal microorganisms from an adult turkey. Each preparation protected both avian species when administered orally prior to challenge, but the degree of protection obtained varied with the type of preparation and its host origin. PMID- 1419530 TI - Defined cultures and prospects. AB - Resistance of young chicks to Salmonella colonization can be increased by treating them with suspensions or anaerobic cultures of gut content from healthy, adult birds. Unfortunately, such treatments have an unknown bacterial composition and are therefore not acceptable to regulatory agencies in some countries. Efforts are continuing to identify components in the gut microflora that are involved in the protective process. The ultimate aim is to identify bacteria that may be used, either alone or in mixtures (defined cultures), as a prophylactic treatment of chicks against Salmonella colonization. Although much research has been done in this area, a defined culture treatment with a potency and stability equivalent to that of undefined culture has not been developed. Since the mechanism of protection is not clear, there are no reliable criteria for selecting potentially protective strains. The most effective mixtures contain large numbers of bacterial cultures (about 50 isolates). These mixtures are comparable to undefined faecal cultures in protecting chicks against challenge levels of up to 10(4) Salmonella/chick. However, they are not protective for turkey poults. Mixtures containing lower number of strains are generally less protective. It appears that obligate and facultative anaerobes from different genera are required for protection. Mixtures containing strains from only one genus, e.g. Lactobacillus or Bifidobacterium, are generally not effective. Maintenance of intestinal isolates on laboratory media, as well as in storage at 70 degrees C, results in a progressive decrease in their protective ability. The protective ability of mixtures or individual strains can be partially restored by in vivo passage. A promising criterion for isolating and/or screening potentially protective isolates is based on the adherence of native microflora to the caecal wall of treated chicks. Despite substantial efforts and some progress in the development of defined cultures, the prospects are not very encouraging. Until the exact mechanism of protection is elucidated, the basis for selecting the required strains will be difficult to define. PMID- 1419531 TI - Competitive exclusion of campylobacters from poultry with K-bacteria and Broilact. AB - The competitive exclusion (CE) product (Broilact) which is effective against Salmonellas, was found to be inactive against campylobacters. Microecological concepts were applied in the search of a new competitive flora and two novel strains ('K-bacteria') were isolated. These strains resembled campylobacters but differed from them in morphology, enzyme profiles (API), cellular fatty acid profiles and when tested with a ribosomal RNA hybridization probe (Gene-Trak). Two-week laboratory trials on broiler chickens showed that CE treatment may protect the birds against campylobacters but revealed the need for facultatively anaerobic bacteria in establishing a protective flora. A 5-week pilot scale trial was carried out. The trial involved 1800 newly hatched chicks in 30 groups. K bacteria and Broilact, which provided the necessary facultatively anaerobic bacteria, were administered to some of the birds in the first drinking water. A seeder bird technique was used to challenge experimental and control birds with Campylobacter jejuni biotype 2 (broiler origin). Three seeder birds were placed in each group of 60 birds. Groups were sampled weekly for campylobacters and finally at the slaughterhouse. From each group, the caecal contents of two birds were examined quantitatively for campylobacters. The performance of the birds was also monitored during the trial. The results showed a 1.5 week delay in the onset of campylobacter infection in treated chicks and a consistently lower level of colonization in comparison with control birds. At slaughter, levels of carriage in caecal contents of treated birds were 1.5-2.0 log10 units lower than those of controls, despite apparent stress from harvesting and transportation. The treatment had no economically important effects on the performance of the birds during rearing. PMID- 1419532 TI - Antimicrobials and competitive exclusion. AB - The compatibility of commonly used antimicrobial feed additives with CE treatment are examined. It appears that additives permitted in the U.K. are without effect on CE, with the possible exception of avoparcin. However, a sharp difference has been found with the effect of antimicrobials on CE treatment cultures in vitro, and the in vivo effect; and it is postulated that these differences may be accounted for by the fact that the substances may not be 'caecum available' in the bird. When effects are observed in the bird they appear to be largely due to dose variation. In the case of adult birds already infected with Salmonella, the time lapse between completion of antimicrobial treatment and the administration of Broilact will be examined; as well as the selection of appropriate antimicrobial treatment in infected birds prior to the administration of replacement microflora. PMID- 1419533 TI - Long-term experience with competitive exclusion and salmonellas in Finland. AB - Poultry production is under strict official control in Finland. Fifteen years after the introduction of 'competitive exclusion' treatment the majority of growers (over 70%) use it routinely. The number of Salmonella-positive flocks is less than 5% and the incidence of Salmonella-contaminated broiler carcasses has been 5-11% in the last two years. The average number of Salmonella cells on contaminated carcasses is very low, generally less than 5 per carcass. Between 70 and 80% of human Salmonella infections are contracted abroad, mainly outside the Nordic countries. It is estimated that only 15-20% of some 1200 cases of domestic origin are caused by contaminated poultry. PMID- 1419534 TI - Experience of a 10-year use of competitive exclusion treatment as part of the Salmonella control programme in Sweden. AB - In Sweden, competitive exclusion (CE) treatment has been used since 1981 as a part of the national control programme for Salmonella. According to the programme all broiler flocks are tested for Salmonella before slaughter thus providing an evaluation of CE treatment. The CE culture used is mainly for the two consecutive flocks raised in a unit after a Salmonella-infected flock has been identified. During the period 1981-1990 Ce culture has been given to 179 flocks, involving 3.82 million chickens. Only one of the treated flocks was found to be Salmonella positive. A special study during a period when Salmonella was spread by contaminated feed demonstrated that CE treatment was effective in controlling Salmonella under field conditions. A likely contributory factor is that the hatcheries in Sweden can be claimed to be Salmonella-free. In addition, the control programme and related action, have led to a very low incidence of Salmonella in broiler chickens. A nationwide study carried out in 1990 demonstrated that less than 1% of broiler chickens was contaminated with Salmonella after slaughter. PMID- 1419535 TI - The use of an antimicrobial and competitive exclusion combination in Salmonella infected pullet flocks. AB - Replacement pullets which had been found infected with Salmonella were treated with antibiotics for 12 days, moved to a clean house by the 11th day and given 2 treatments with a competitive exclusion (CE) preparation on the 13th and 15th day. It was found necessary to supply a small amount of feed to generate a thirst in the birds and ensure efficient and rapid consumption of the CE preparation. Salmonella could not be grown from the intestines or other organs of birds after this procedure had been carried out. PMID- 1419536 TI - Use of a competitive exclusion product (Broilact) to prevent Salmonella colonization of newly hatched chicks. AB - The study described here was carried out at the request of a French company to utilize the authors' experience of 'competitive exclusion' treatment for poultry. The objective of the study was to determinate the safety and efficacy of a particular treatment product (Broilact) in protecting chicks against Salmonella infection. PMID- 1419537 TI - Prevention of colonization by Salmonella enteritidis PT4 in broiler chickens. AB - Field experiments in The Netherlands and in Scandinavian countries have shown that an undefined microflora originating from SPF adult poultry will reduce considerably the colonization of young chicks by Salmonella. A commercial product from this so-called Nurmi concept, Broilact, was studied for its effectiveness in preventing infection of broilers with Salmonella enteritidis PT4 (S.e.). Two trials were carried out, in which the birds were exposed to S.e. via 'seeder' birds placed among them. The trial period was 21 days and each week one third of the chicks was killed and their caecal contents examined for salmonellas. The results of the first trial can be summarized as follows. (1) After 2 weeks the number of 'seeder' birds carrying the Salmonella decreased sharply; (2) the proportion of infected chicks in the Broilact-treated group was lower than in the non-treated group; (3) Counts of S.e. in the non-treated group were higher than in the Broilact group. Results of the second trial were comparable, although no salmonellas could be isolated after the second week. PMID- 1419539 TI - Survey of thermotolerant Campylobacter spp. and Yersinia spp. in three surface water sources in Norway. AB - We investigated the occurrence of thermotolerant Campylobacter and Yersinia spp. in three surface water sources in Norway which represented different levels of pollution and eutrophication. Samples were collected every fortnight during a 14 month period. In addition, samples from 100 private wells were examined for campylobacters only. Campylobacter was recovered from 42 (43.8%) of the 96 samples of surface water, whereas Yersinia spp. were isolated from four (4.2%) of the samples. Campylobacter was not isolated from the well water samples. The highest isolation rate of Campylobacter was obtained from the two most polluted water sources. The proportion of positive samples was significantly higher in the autumn (71.4%) than in the spring (36.4%) or summer (22.2%). The highest overall isolation rate was obtained at water temperatures ranging from 2.1 to 8.0 degrees C, and the lowest at temperatures greater than 15 degrees C. Logistic regression analysis showed a highly significant relationship between the prevalence of Campylobacter and the number of three types of indicator bacteria: faecal coliforms, faecal streptococci and sulphite-reducing clostridia. Of the 60 Campylobacter isolates obtained, 51.7% belonged to C. jejuni biotype 1, 20.0% belonged to C. jejuni biotype 2, 21.7% to C. coli, 3.3% to C. lari and 3.3% were non-typable. All four Yersinia isolates were non-pathogenic variants. PMID- 1419540 TI - Behavior of Listeria monocytogenes during processing and storage of experimentally contaminated hot-smoked trout. AB - Hot-smoked fish like smoked trout is quite frequently contaminated with Listeria monocytogenes. In order to estimate the potential health hazard for the consumer eating such products, the behavior of L. monocytogenes was studied during processing and storage of artificially-inoculated hot-smoked trout. Four trials were performed; in trials 1 and 3 a wild-type strain was used, while in trials 2 and 4 a serological reference strain, SLCC 2755, was used. In the first two trials, raw trout was surface inoculated with L. monocytogenes, marinated, hot smoked (core temperature 65 degrees C during 20 min), and stored at 4 and 8-10 degrees C, respectively, for up to 20 days. At different times during processing and storage, samples were taken and, by means of a MPN-method, quantitatively analysed for L. monocytogenes. The initial Listeria levels in the trout were 10(6) MPN/g. Until smoking, the concentrations remained about the same. After the hot-smoking process and during storage, however, L. monocytogenes could no longer be detected. In trials 3 and 4, the trout were inoculated after hot-smoking at a final concentration of 4.5 x 10(1) MPN/g and 3.1 x 10(1) MPN/g, respectively. During storage at 4 degrees C, neither an increase nor a decrease of L. monocytogenes was observed. At 8-10 degrees C, however, a significant increase up to 10(7) MPN/g occurred. By hot-smoking, low level contaminations of raw fish with L. monocytogenes will easily be eliminated. Nevertheless, it is of great importance to prevent postprocessing contamination, because during storage at refrigeration temperatures growth of L. monocytogenes is possible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419538 TI - Evaluation of the efficacy of Broilact in preventing infection of broiler chicks with Salmonella enteritidis PT4. AB - A study was conducted to evaluate treatment of day-old broiler chicks with Broilact, a live-culture preparation, for preventing intestinal colonization by a non-host-specific Salmonella (S. enteritidis PT4, with high resistance to nalidixic acid). Newly hatched broiler chicks were sprayed with Broilact at a commercial hatchery and delivered on the same day to Huntingdon Research Centre. Control chicks from the same source (i.e. chicks not treated with Broilact) were sent separately. Chicks were maintained in floor pens in groups of 40. The challenge was introduced by means of seeder birds infected with S. enteritidis PT4 (nalr) at a nominal dose level of 10(4) CFU per bird (3 seeder birds per pen of 40 contact birds). Groups of birds were killed 7, 28 and 40 days after challenge, and in each case caecal contents were examined culturally for the test organism. A total of 18 deaths occurred including 13 untreated contact birds, 3 Broilact-treated contact birds and 2 seeder birds. These were attributed to the experimental infection. Results of the examination of caecal contents from untreated control birds indicated that the challenge organism was successfully established in contact chicks via the seeder birds. The overall results for birds treated with Broilact showed a clear protective effect, with little indication of any significant infection by the challenge organism. It was concluded therefore that under the conditions of this study, Broilact was largely effective in preventing intestinal colonization by the non-host-specific s. enteritidis PT4. PMID- 1419541 TI - Infectivity of Toxoplasma gondii in mutton following curing, smoking, freezing or microwave cooking. AB - To investigate the effects of curing with sodium chloride and sucrose, low temperature smoking, freezing at -20 degrees C, and cooking in a microwave oven, respectively, on the infectivity of Toxoplasma gondii encysted in mutton, meat from three experimentally and one naturally infected sheep was used. Samples of meat prepared accordingly as well as untreated, raw meat from each animal were assayed by mouse inoculation. Infective T. gondii was isolated from untreated samples from all animals used, but in no case from cured, smoked or frozen meat. However, in two of four steaks processed in a microwave oven, according to a standard household recipe, the parasite remained infective, possibly due to uneven heating of the meat. PMID- 1419542 TI - Glucose and sucrose fermenting capacity of homofermentative lactic acid bacteria used as starters in fermented salads. AB - Salads, i.e., vegetables and/or meat in an oil-in-water emulsion with a low pH due to the addition of acids, are popular in western countries. The shelf life of these salads is influenced mainly by storage temperature and the use of preservatives, i.e., sorbic and benzoic acid. Lactic acid fermentation could be an interesting novel approach to salad preparation. As part of an investigation on fermented salads, lactic acid bacteria from the genera Lactobacillus, Pediococcus and Streptococcus were screened for their capacity to ferment glucose and sucrose in a model system and in a standard salad. The temperature optimum of these strains was in the range of 34-48 degrees C. Most of these strains produced about equal amounts of L(+)- and D(-)-lactic acid. To determine the specific sugar fermenting capacity (mmol lactic acid produced per min per g dry weight) of non-growing cells of lactic acid bacteria, a semi-automated model system was used, based on monitoring the pH decrease in a phosphate buffer during conversion of sugars to lactic acid. The strains tested showed acid production rates on glucose varying between 0.03 and 0.39 mmol of acid produced per min per g dry weight (average 0.23). These glucose-grown cells showed varying, but lower fermentation rates on sucrose (0-0.25 mmol/min/g d.w., average 0.04) than sucrose grown cells (0-0.33 mmol/min/g d.w., average 0.19). Results obtained with the model system were in good agreement with those of fermentation tests, carried out with a standard salad. Inhibition of spoilage bacteria in the standard salad could be achieved by using starter cultures with high fermenting capacity. PMID- 1419543 TI - Simple and economical culture of Campylobacter jejuni and Campylobacter coli in CO2 in moist air. AB - Strains of Campylobacter jejuni and C. coli representing the 18 serogroups (Lior) most commonly isolated from humans in Canada were grown on solid media in an atmosphere of 10% CO2 in moist air, 99% relative humidity. When the growth of all 18 serogroups on Mueller Hinton agar in a microaerobic atmosphere (5% O2, 10% CO2 and 85% N2) was compared with the growth of all 18 serogroups on the same media in 10% CO2 in moist air, colony sizes were significantly larger (p less than 0.05) for strains grown in 10% CO2 in moist air. No significant difference in colony numbers was seen between the two atmospheres. The addition of blood to the media significantly enhanced the growth of the campylobacters in both types of atmospheres (p less than 0.05). This simple CO2 atmosphere permitted the use of a common CO2 incubator thereby reducing the cost and difficulty of culturing these organisms. PMID- 1419544 TI - Growth of fermentative and non-fermentative yeasts in natural yoghurt, stored in polystyrene cartons. AB - Permeation of oxygen through polystyrene packaging is a factor in the growth of yeasts in natural yoghurt. Diffusion of oxygen through the packaging material can permit the growth of non-fermentative yeasts in yoghurt stored at refrigeration temperatures. Yarrowia lipolytica, a non-fermentative yeasts which does not utilize lactose was isolated from yoghurt. The growth in natural yoghurt of Yarrowia lipolytica and the lactose-fermenting yeast Kluyveromyces marxianus was investigated. Both yeasts grew in yoghurt with reduced fat content. Storage of yoghurt in an anaerobic atmosphere eliminated growth of Yarrowia lipolytica but permitted fermentative growth of Kluyveromyces marxianus. PMID- 1419545 TI - An audit of trauma deaths in Newcastle upon Tyne. AB - The TRISS methodology was applied to identify unexpected trauma deaths during a one-year period. Out of a total of 104 deaths, 50 were hospital deaths (M = 0.6837). Twelve (27%) of these deaths were judged to be unexpected, ie, had a probability of survival (Ps) > or = 0.50 (Z = +4.80). Those deaths deemed to be unexpected were subject to further analysis. The implications of these findings are discussed. PMID- 1419546 TI - A survey of head injuries in a general hospital. AB - This paper reports the incidence of head injuries as patients attended a general hospital Accident & Emergency Department. The survey was carried out over a twelve-month period. The Accident & Emergency Department of Luton & Dunstable Hospital sees approximately 60,000 new patients every year. It is situated in close proximity to the M1 motorway and other major road systems. Facilities are available on site for computerised tomography from Monday to Friday between 9:00 am and 5:00 pm. At other times, if it is considered necessary after consultations with our neurosurgical colleagues, they are referred to the Royal Free Hospital, 30 miles away. PMID- 1419547 TI - Childhood chronic renal failure in Qatar. AB - Thirty children below the age of 12 with chronic renal failure (CRF) were studied. In 21 patients (70%) the renal failure was secondary to congenital or familial aetiology. Obstructive uropathy (53.3%), mostly due to posterior urethral valves (40%), comprised the majority of cases. Four cases (13.3%) were secondary to reflux nephropathy. It is concluded that the majority of cases of CRF in the state of Qatar are secondary to potentially treatable or preventable conditions. Use of antenatal ultrasonography combined with aggressive management of obstruction and urine infection may help reduce morbidity and mortality. PMID- 1419548 TI - Fluvoxamine in the treatment of depressive illness. A series of double-blind hospital based comparative studies carried out in the UK. AB - A series of double-blind hospital based studies comparing fluvoxamine with other antidepressants in depressed patients is reviewed. Overall there were no significant differences in terms of efficacy between fluvoxamine and the comparators (amitriptyline, dothiepin, lofepramine and mianserin). Fluvoxamine was shown to be associated with a low incidence of anticholinergic, cardiovascular or sedative effects. This profile of activity, together with low toxicity in overdosage, has established the place of fluvoxamine in the treatment of depressive illness. PMID- 1419549 TI - Comparative efficacy and tolerability of cephradine and cefuroxime axetil in the treatment of acute dysuria and/or frequency in general practice. AB - One hundred and thirteen patients with dysuria and/or frequency were treated randomly with either 500 mg cephradine 12-hourly or 125 mg cefuroxime axetil 12 hourly, for seven days. A total of 71 patients were found to have urinary infection: bacteriological cure rates were 97% one week post-treatment, and 96% five weeks post-treatment, for both antibiotics. On direct questioning, adverse events were reported by eight patients out of 59 taking cephradine and by three of 54 who had received cefuroxime axetil. However, only three and one respectively stopped taking the antibiotic due to the adverse event. Analysis of diary cards, completed by 109 patients, showed a significantly higher incidence of increased frequency of bowel movements in those taking cefuroxime axetil. It is concluded that both antibiotics are of equal value in the treatment of simple acute urinary infections in general practice. PMID- 1419550 TI - Doctors' knowledge of socio-legal aspects of patient care. AB - Doctors' knowledge of socio-legal aspects of patient care is poor. To quantify this a questionnaire on certain socio-legal topics was sent to 400 general practitioners and 250 hospital doctors. The responses were compared to a group of social workers. Both hospital doctors and general practitioners did badly on all topics considered. Social workers' knowledge was significantly better overall, (P < 0.01). Our results confirm the lack of knowledge amongst a broad spectrum of doctors. We suggest that this may be related to a lack of emphasis on these aspects in both undergraduate and postgraduate education. PMID- 1419551 TI - Ofloxacin versus trimethoprim and co-trimoxazole in the treatment of uncomplicated urinary tract infection in general practice. AB - A large-scale, randomised, multicentre single-blind clinical trial was conducted to assess the comparative efficacy and tolerance of ofloxacin, trimethoprim and co-trimoxazole in the treatment of uncomplicated urinary tract infection in general practice. A total of 1,069 patients from 76 centres across the UK were enrolled in the study, and randomised to one of the following treatment groups: ofloxacin (200 mg od), trimethoprim (200 mg bd) or co-trimoxazole (trimethoprim 160 mg and sulphamethoxazole 800 mg bd). Each patient received five days of medication. Clinically, ofloxacin was as effective as trimethoprim and co trimoxazole. However, the bacteriological cure rate was significantly better for ofloxacin, with eradication of the initial causative pathogen by the end of treatment in 92% of patients in the ofloxacin group, compared with 81% for trimethoprim and co-trimoxazole (P = 0.0002). There was also a lower relapse rate for ofloxacin. Ofloxacin was well tolerated: adverse events were reported by 67 (12.4%) patients in the ofloxacin group, compared with 48 (18.7%) patients in the co-trimoxazole group and 37 (13.6%) patients in the trimethoprim group. Ofloxacin can therefore be considered a suitable alternative for the treatment of uncomplicated urinary tract infection. PMID- 1419552 TI - Sleep apnoea: causes, consequences and treatment. AB - An awakening has taken place over the last 25 years to the science of sleep disorders. Foremost amongst these, both in the medical world and the public eye, has been Sleep Apnoea Syndrome (SAS). The prevalence is thought to be the order of 1-2%. Males are eight times more commonly affected than females, although after the menopause the gap narrows considerably. Sleep apnoea occurs in children, usually in relation to large tonsils and adenoids, but in adult life patients usually present between the age of 40 and 60 and the prevalence increases with age. Numerous apnoeas or hypopnoeas during the night's sleep result in disordered sleep architecture and unrefreshing sleep. This is usually accompanied by night-long snoring which may lead to marital discord and even complaints from neighbours. Symptoms on waking may be a headache and a feeling of not being refreshed by sleep. Sleepiness during the day can interfere with work and social activities and may produce risks to the patient and others if it occurs while operating dangerous machinery or driving. Over a longer time scale SAS results in intellectual and memory deterioration, a higher incidence of ischaemic heart disease, hypertension, polycythemia and pulmonary hypertension. Right heart failure is particularly likely if there is chronic airflow obstruction contributing to a low arterial oxygen level. Asystolic periods and tachyarrhythmias may occur during apnoeic periods. The increased mortality of SAS relates to coronary and cerebrovascular disease and arrhythmias. Sudden death occurs with greater frequency in patients with SAS, mainly at night. PMID- 1419553 TI - Coronary intervention: where are we now? AB - Coronary interventional techniques are used widely in the treatment of patients with coronary artery disease. With modern dilatation equipment the angiographic success rate of coronary balloon angioplasty may exceed 90%, but complications due to acute coronary occlusion may require emergency coronary artery bypass surgery (2-4%), or result in acute myocardial infarction (2-5%) or in-hospital death (0-2%). In most patient groups the long-term outcome of successful coronary angioplasty is good, but restenosis of a successfully dilated stenosis occurs in about 30% of cases, necessitating re-intervention in a significant proportion of patients. Other interventional methods of treating coronary artery stenosis, including directional and rotational coronary atherectomy, endoluminal stenting, and laser angioplasty, have been used in preliminary clinical studies. The acute results of these techniques are encouraging but the restenosis rate remains high and the long-term results are uncertain. The results of randomised clinical trials comparing coronary interventional techniques with alternative treatment methods are awaited. PMID- 1419555 TI - Conservative therapy for tennis elbow. AB - Tennis elbow is a common overuse syndrome. It is accompanied by degenerative changes in the enthesis of the extensor carpi radialis brevis muscle. It may be best diagnosed clinically by eliminating other possible causes of lateral elbow pain. Physical methods should always be selected as initial treatment. Immobilisation is the initial advice that most doctors give: ultrasound has been shown to be effective in a placebo-controlled, double-blind trial, and low energy laser has been found to reduce objective but not subjective symptoms. Other forms of physical treatment like electrotherapy, thermotherapy and massages can be tried, even though proof of their efficacy needs to be established more firmly. When physical treatments have failed, steroid injections can help. If symptoms still persist, then surgery is called for. There are still many open questions surrounding the syndrome of tennis elbow. Research into this common soft tissue disease should be intensified. PMID- 1419554 TI - Ectopic pregnancy: epidemiology, advances in diagnosis and management. PMID- 1419556 TI - Which calcium channel blocker for ischaemic heart disease? AB - Calcium channel blockers have been available since the early 1960s. Extensive research has been undertaken to evaluate their usefulness in the treatment of patients with ischaemic heart disease. We have reviewed the pharmacology of these drugs and the major clinical trials. In particular, we have examined the effect of calcium channel blockers on the progression of atheroma, and their role in the following clinical settings: following myocardial infarction, following non-Q wave myocardial infarction, and in unstable angina. PMID- 1419557 TI - The management of aortic aneurysms. PMID- 1419558 TI - Artificial ventilatory management in a severe, pregnant asthmatic--a case report. AB - A 33-year-old pregnant atopic woman, who had never suffered from asthma or atopic related disorder, was admitted on three occasions during her fifth pregnancy with severe asthma. On her last admission she required more intensive monitoring and artificial ventilation. We report this patient and discuss the pathogenesis of asthma during pregnancy. Asthma in pregnancy is not uncommon and it may take a severe course in some pregnancies. In one prospective study 42% of the patients required aggressive management, but none required artificial ventilation. However, there was no difference in the outcome of pregnancies between asthmatic and control subjects. Here we describe a patient with severe asthma who required artificial ventilation with a successful outcome. PMID- 1419559 TI - Paradoxical emboli in elderly patients. AB - We report two elderly patients who each had a patent foramen ovale (PFO) and were considered to have had paradoxical emboli. In one patient the PFO was detected by contrast two-dimensional echocardiography, whereas in the other it was demonstrated at post-mortem examination. This is an unusual but treatable condition, particularly difficult to diagnose in older people and probably occurring more frequently than is generally suspected. PMID- 1419560 TI - Spontaneous rupture of normal spleen: an enigma recalled. AB - That a normal spleen can rupture spontaneously has long been a point of debate. A definitive case is reported here in an attempt to resolve the issue in its favour. Spleen involved in tropical diseases like malaria, infectious mononucleosis and typhoid fever is prone to rupture spontaneously as well as in cases follow minor trauma. In contrast, normal spleen ruptures almost always following severe trauma, such as road accidents or fall from significant heights. Though cases of spontaneous rupture of normal spleens have appeared off and on in the past, doubt has always surrounded the very existence of such an entity. We are reporting a definitive case of spontaneous rupture of normal spleen. This is only the second case of its kind since 1958 and the first ever from the Indian subcontinent. PMID- 1419561 TI - Recurrent endometrial adenocarcinoma presenting as an umbilical metastasis (Sister Mary Joseph's nodule). AB - A case of recurrent endometrial adenocarcinoma metastatic to the umbilicus is reported. The possible modes of spread, management and prognosis of this rare manifestation of visceral malignancy are discussed. PMID- 1419562 TI - Extra cranial arteriovenous malformations presenting as pulsatile tinnitus. AB - We present two cases of extra cranial arteriovenous malformations, which presented as pulsatile tinnitus. They were originally diagnosed by clinical examination and both lesions were subsequently confirmed by angiography and their feeding vessels defined. One case was managed by surgical excision, which produced relief of symptoms. The diagnosis and management of arteriovenous malformations is discussed. PMID- 1419564 TI - Crossed ectopic pelvic kidney with duplication. PMID- 1419563 TI - Ruptured abdominal aortic aneurysm presenting with acute urinary retention. AB - Ruptured abdominal aortic aneurysm classically presents with abdominal pain radiating to the back, a pulsatile abdominal mass and circulatory collapse. However, other symptoms may be the only presenting complaint. We report the case of a patient who presented with a history of acute retention of urine relieved by catheterisation, but who then developed clinical features more typical of abdominal aortic aneurysm rupture. PMID- 1419565 TI - Incarcerated fallopian tube. PMID- 1419566 TI - Meningitis: a neurosurgical disease. PMID- 1419567 TI - Expanded programme on immunization. PMID- 1419568 TI - Fascioliasis. PMID- 1419569 TI - Cerebrospinal meningitis in the Central African Republic. PMID- 1419570 TI - Expanded programme on immunization. Poliomyelitis outbreak. PMID- 1419571 TI - Global health situation. PMID- 1419572 TI - Expanded programme on immunization. Poliomyelitis outbreak. PMID- 1419573 TI - Update: International Task Force for Disease Eradication. 1992. PMID- 1419574 TI - Haemochromatosis. PMID- 1419575 TI - Cancer prevention education in United States medical schools. Cancer Education Survey II: cancer education in United States medical schools. AB - The Cancer Education Survey collected data from 126 of 128 US Medical Schools on the current status of cancer-related educational activities for undergraduate medical students. The study was conducted by a Supervisory Committee of the American Association for Cancer Education, with funding from the American Cancer Society. The survey obtained data concerning institutional characteristics in support of undergraduate medical student cancer education, ie, administrative structures, current cancer-related curricula, sources of financial support, and anticipated changes in these characteristics. Institutions were also queried on specific topics of cancer prevention, detection, and diagnosis that might be taught as identifiable areas of instruction for medical students. Three-fourths of the institutions had a lecture on the principles of cancer screening, and, among those, nearly three-fourths classified it as a part of a required course or rotation. Detection of common cancers is taught in virtually all institutions. The least likely cancer prevention lecture topics are related to prevention and cessation of smoking, a well-verified cancer risk. Also, no consistent pattern emerges that might indicate that association with a cancer center imparts to a medical school a greater emphasis on delivery of cancer prevention topics. PMID- 1419576 TI - Changing the cancer curriculum: a curriculum committee's response to the results of the AACE Cancer Education Survey II. Cancer Education Survey II: cancer education in United States medical schools. AB - The AACE Cancer Education Survey-II offers an unusual opportunity based on data from 125 medical schools and 1,035 experienced cancer educators to effect constructive change with regard to cancer education. The changes suggested include more coordination; integration; and a shift of emphasis to include more on topics of prevention, early diagnosis, tumor biology, rehabilitation, palliative care, and psychosocial issues. Ample opportunities, especially in the ambulatory care arena, exist at most medical schools, and there is a great deal of interest in improving the situation. This article reviews the factors contributing to resistance to change, the data on adult learning, and the major movements and dilemmas facing medical education today. It also discusses some of the external forces like the Liaison Committee on Medical Education (LCME) and foundation support, which are being harnessed to effect change. Given these barriers, forces, and opportunities, the article ends with a possible action plan for an individual, an institution, and national bodies interested in cancer education. The knowledge, skills, values, and attitudes must be defined, taught effectively, and evaluated. It is an opportune time, armed with this useful data, to bring about change in how cancer subjects are taught. The ultimate goal is more knowledgeable and effective practitioners and scientists who can decrease the morbidity and mortality from cancer. PMID- 1419578 TI - A multidisciplinary educational program to promote head and neck cancer screening. AB - An educational program to promote screening through primary health care for the squamous cell cancers of the buccal cavity, pharynx, and larynx as developed and implemented, and its impact on screening was documented. Providers of care for high-risk patients at seven inner-city health care sites in Boston were identified and targeted for training. Of the 327 providers who were targeted for training from December 1986 through June 1989, 261 (80%) attended educational sessions. Screening exams were documented on an average of 14.7 patients per targeted provider through December 1989. The educational program was associated with a large increase in documented screening for these cancers, compared with baseline rates. Several adaptations in the program were required, including a demonstration of efficient screening to address the concerns of these providers about time constraints. Variations in the quantity and quality of documented screening among health care sites were noted. PMID- 1419577 TI - A meal conference format to teach ambulatory nutrition concepts. AB - Third-year medical students participated in a program using a meal conference approach to teach ambulatory nutrition concepts called "Building Better Health Through Nutrition." The series of three interactive presentations was given during the required family medicine clerkship. A pretest and posttest were used to measure acquisition of nutrition knowledge. There was a statistically significant (P less than 0.05) average increase in posttest compared to pretest scores. Seventy percent of students rated the meal conference approach as "effective" or "very effective" and 76% stated that the series expanded their knowledge of nutrition's role in clinical medicine. We conclude that the meal conference format is an effective way to teach nutrition during the clinical years in medical school. PMID- 1419579 TI - Physician/patient communication: a model considering the interaction of physicians' therapeutic strategy and patients' coping style. AB - During the last decade, several studies have demonstrated the importance of information-seeking versus information-avoiding coping styles of cancer patients receiving educational information from their physician. During the same period of time other studies have demonstrated important differences in the communicative style of oncologists providing educational information to their patients. However, the implications of the interaction of these two areas of research have not been systematically considered. We present here a hypothetical model concerning the implications of physicians with different communicative styles interacting with patients with different coping styles. PMID- 1419580 TI - Teachers' attitudes to cancer education: a discussion in the light of a recent English survey. AB - Various attempts have been made at encouraging cancer education in British schools, and while some have had limited success, there is still a reluctance amongst teachers to adopt this subject in the classroom. The study discussed in this paper was an attempt to ascertain the current status of cancer education in English secondary education. Over 1,200 English secondary (11-16 years olds) schools took part and the data were collected between February and June 1990. Although there is evidence to suggest an element of self-selection, results from this sample indicate a growing commitment and enthusiasm for cancer education, in comparison to previous, similar studies. Over half the teachers had taught about cancer and 68.8% rated it an important health education topic. However, cancer did rate lowest out of a variety of health issues. Several reasons for this are discussed and all appear to relate to teachers' negative attitudes toward cancer, apparently based on preconception and misinformation. These must be overcome if cancer education is to achieve its true potential in English schools. PMID- 1419581 TI - Survey design and observations relating to cancer education funding. Cancer Education Survey II: cancer education in United States medical schools (conducted by The American Association for Cancer Education with the support of the American Cancer Society). AB - A survey has been conducted of cancer education programs for medical students in United States medical schools by the American Association for Cancer Education with grant support from the Department of Detection and Treatment of the American Cancer Society (formerly the Professional Education Department). Two questionnaires were used, an Educational Resources Questionnaire (ERQ), which 126 of the 128 medical schools completed and returned, and a Faculty and Curriculum Questionnaire (FCQ), which was completed and returned by 1,035 faculty members who had been named as active in undergraduate medical student cancer education by respondents in each school who had been designated by the Dean's Office to complete the ERQ. Overall conclusions included: (1) increased coordination of cancer education activities is a major need in many schools; (2) there is widespread interest in the further development of cancer education objectives; (3) development of a national cancer education curriculum is needed; (4) there is interest in the development of improved instructional materials and methods; (5) development of evaluation methods is needed for cancer education programs; and (6) an ongoing funding process is needed to provide support for interdepartmental coordination of cancer education activities. Cancer prevention and detection topics were ranked above cancer treatment in plans for future curriculum emphasis. More detailed conclusions and recommendations are provided in this publication and three subsequent articles in this issue of the Journal of Cancer Education. PMID- 1419583 TI - "It is still a privilege to be ..." an oncologist. PMID- 1419582 TI - Instructional methods and the use of teaching resources in cancer education curricula. Cancer Education Survey II: cancer education in United States medical schools. AB - The findings on cancer teaching methodology presented in this abstract come from an American Association for Cancer Education (AACE)/American Cancer Society sponsored survey of American allopathic medical schools in 1989 and 1990 to determine how and how well cancer is presented in the medical school curriculum. Responses were received from 126 institutional and approximately 1,000 faculty respondents. Approximately one-third (368) of faculty respondents indicated the use of specific learning objectives; utilization does vary across disciplines. The lecture remains the dominant form of instructional method. Computers were reported as an instructional modality by only 16% of the faculty respondents. Prepared audiovisual instructional materials appeared to be widely utilized. Use varied from 86% for 35mm slides to 11% for video discs. Faculty favored the development of new teaching materials for ten topic areas ranging from approximately 40% for early detection and prevention to a low of approximately 25% for rehabilitation and continuing care. The survey identified an underutilization of existing outpatient facilities and tumor registries for cancer teaching purposes. The findings give rise to questions concerning the appropriateness of the match between specific instructional goals and the teaching methods employed. Eight recommendations designed to strengthen cancer training are made. PMID- 1419584 TI - New standards for commercial support of CME: where are we headed? PMID- 1419585 TI - Clinical research--a commentary. PMID- 1419586 TI - Enhancing the level of nutrition education at Tufts University's Medical and Dental Schools. AB - The current medical and dental curricula at Tufts were evaluated to ascertain the breadth and depth of their nutrition programs. The program, which both schools plan to initiate, to enhance the level of nutrition education involves (1) development of nutrition units for the first and second year, (2) expansion of required nutrition courses in the second year, (3) diet lunches in the third year introducing the role of nutrition in the clinical setting, and (4) nutrition rounds in the fourth year. A combined medical-dental seminar will be presented each year. At the end of the five-year funding period, it is anticipated that a manual will be available to all medical and dental schools that includes (1) nutrition units, (2) methods of dietary assessment in medical-dental practices, (3) nutrition interaction for the prevention of chronic disease in medical-dental practices, and (4) nutrition support for chronic disease and cancer, and case studies on nutrition and disease. The success of this program will be evaluated on the basis of goals and a national nutritional literacy exam. PMID- 1419587 TI - Dental student education in oncology: design and assessment of an undergraduate course. AB - Five-year survival rates of oral cancer patients remain poor. To better prepare undergraduate dental students to recognize this problem and contribute to solutions, a 24-hour lecture course in oral oncology was instituted. A pre-course quiz, daily quizzes, a midterm and a final examination were administered to assess student knowledge. The course covered all aspects of oral cancer from epidemiology and etiology, through diagnosis, treatment, and rehabilitation. Student oncology knowledge was assessed by analyzing the test results of two consecutive third-year dental classes. Overall, students adequately meet the course objectives, but assessment of specific topics reveal some deficits in particular areas. Evaluation of student knowledge provides valuable information to instructors for improving course content and student achievement. PMID- 1419588 TI - Defining and accomplishing clinically related objectives in an eight-hour oncology course for first-year medical students. AB - Designing a clinically relevant cancer curriculum for freshmen attending medical schools with a traditional curriculum poses the following challenges: (1) there is limited curriculum time; (2) the subject matter is complex. The authors defined some of the responsibilities of the general physician in regard to cancer and six related objectives that first-year students could accomplish in an eight hour multidisciplinary oncology course. A case-based, modified essay examination required students to demonstrate that they could begin to integrate principles of prevention, screening, diagnosis and staging, and treatment modalities. Ninety percent of the students accomplished the objectives. However, in working up the cancer case, 70% of the students did not mention the physical examination and 53% forgot multidisciplinary consultation. In a curriculum with limited objectives, first-year students can begin to deal efficiently with the complexities of cancer. Evaluation data revealed those objectives and related physician responsibilities requiring reinforcement in subsequent training. PMID- 1419589 TI - The effect of breast clinic participation on the education of third-year medical students. AB - Traditional methods of teaching concepts of breast disease to medical students have included didactic lectures, patient interviews and examinations in the hospital, and patient-directed rounds with housestaff and attendings. From 1980 to 1987, third-year students at the University of South Carolina School of Medicine participated in these educational experiences and were tested at the conclusion of the eight-week surgical core rotation, utilizing written and oral examinations. Beginning in July 1987, students began participating in a defined weekly Diagnostic Breast Clinic which included in-depth instruction in patient examination techniques, mammographic interpretation, and treatment planning. Results of oral and written examinations, specifically regarding knowledge of breast cancer, were compared between the early and later periods. Significantly improved performance was noted in students exposed to a defined breast clinic experience and strongly supports the integration of specific cancer clinic experiences in undergraduate medical education. PMID- 1419590 TI - Cigarette smoking among young physicians and their approach to the smoking problem of their patients. AB - We have undertaken a survey of 100 interns and 100 residents at University of Ankara Medical School to find out their smoking rates as well as their view of the smoking problem in Turkey and their approach to the patient who smokes. The smoking rate of interns and residents were comparable to those of the 146 nonmedical university students surveyed at the same time (31% and 37% versus 38%). Our results indicate that smoking residents have less confidence in their efficacy to influence the patients to quit smoking when compared to nonsmokers (34.2% versus 14.5%; p < 0.05). Likewise, they have a higher, though not significant, tendency not to counsel their patients than those who are not smoking. Therefore we conclude that a successful smoking cessation program in Turkey requires encouragement of the medical students and residents to quit smoking and better training of them with regard to smoking intervention methods in order to increase their confidence of efficacy. PMID- 1419591 TI - Quality of life and patients with cancer: a comparative study of patient versus physician perceptions and its implications for cancer education. AB - A group of 300 matched pairs of adult patients with cancer (PWC) and their physicians were interviewed concerning the effects of disease and treatment on the patients' quality of life (QL). Patients were asked to rate specific QL factors that concerned them personally, while physicians were asked to evaluate the QL concerns of a hypothetical patient population exhibiting characteristics and diagnoses similar to those of their matched patients. The results indicated that physicians failed to recognize age as a factor having a direct impact upon the QL of their patients. Specifically, physicians estimated that elderly PWC, rather than young PWC, experienced more problems in four out of five QL categories, while in actuality younger patients reported more difficulties in all five categories when compared to their older counterparts. These data suggest that physicians should become more sensitive to the individualized, personal nature of their patients' QL and the factors that may shape or modify it. Implications for cancer education suggest a focus upon determining specific PWC needs as opposed to teaching general QL problems. Students should also be taught not to assume that all PWC experience the same QL concerns; rather, students should be taught to develop a specific history seeking to determine these needs. Finally, educators and students should recognize that young PWC apparently have more difficulty with their disease and its therapy than older PWC. PMID- 1419592 TI - The use of illustrations and narrative text style to improve readability of a health education brochure. AB - Research suggests that much of the available health education literature requires a level of reading ability that makes it inaccessible to a large proportion of the population in greatest need of health information. The present study tested the value of illustrations and a narrative text style as means of improving the readability of a brochure designed to provide information on cervical cancer and condyloma. Two versions of the brochure were designed, one that had only text presented as simple sentences in bullet-type format (SMOG reading level score of 7.7), and a second version that had somewhat more difficult text formatted in a narrative style (SMOG grade level score of 8.4) together with drawings designed to complement the text. A randomized study design was used to test for comprehension, perceived ease of understanding, and overall rating of the two brochures. Women selected from one private and three public health primary-care clinics were randomly assigned to read one of the two brochures. The brochure with illustrations and narrative text was given a significantly higher overall rating than the one with bullet-type text and no illustrations, while no difference was found in perceived ease of reading. Among poor readers, comprehension was significantly greater for women who read the brochure with illustrations and narrative text, with no difference in comprehension of the two brochures for better readers. The results suggest that the use of aids such as illustrations and text style can make health education literature more accessible to high-risk populations, while remaining interesting enough to appeal to individuals at all levels of reading ability. PMID- 1419593 TI - Understanding cultural differences through family assessment. AB - While much has been documented with regard to the role of the family in managing the stress of a diagnosis of cancer, there has been a paucity of attention devoted to cultural differences, which are vital factors in the family's unique ability to cope. Health care professionals in large urban settings are often required to assess families that are unfamiliar to them. This paper focuses on the need to educate health care professionals in order that they can more clearly conceptualize the structure, function, and health-related needs of families from differing cultural backgrounds. Nine interviews with Greek, Chinese, and Italian immigrant families were analyzed retrospectively with regard to family perceptions of hospitalization and experiences surrounding coping and problem solving with respect to a diagnosis of cancer. Findings revealed that fear and loneliness were predominant emotions at the onset of hospitalization. Coping strategies and the management of stress frequency differed from the suggestions of health personnel. This paper concludes that the content of health education curricula needs to be broadened to include attention to cultural considerations. PMID- 1419594 TI - An instrument for measuring cancer patients' preferences for support groups. AB - The purpose of this study was to develop a valid and reliable instrument to assess cancer patients' preferences for all types of social support and organizational features of cancer support groups. The content of the instrument was the result of a detailed analysis of four resources: (1) literature relating to cancer support group interventions, (2) program materials from existing groups, (3) interviews with individuals who developed or directed groups, and (4) interviews with patients who have participated in cancer support groups. A jury of six experts was used to establish content validity of the instrument. The reliability of the instrument was examined by measuring a sample of 258 cancer patients. The reliability coefficients of the instrument were all above .80, except for two types of social support (instrumental and informational educational), which were .72 and .78, respectively. It was concluded that the instrument produces valid and reliable measurements of cancer patients' preferences for cancer support groups. PMID- 1419595 TI - Improving communications in clinical oncology: the EuroCODE project. The EuroCODE Steering Committee. PMID- 1419596 TI - Change in the oestrogen receptor status of breast cancer with age--comparison of two types of assay. AB - The oestrogen receptor (ER) is considered to be an essential component of the mechanism of response of a breast tumour to endocrine therapy, but ER measurements have proved to have only modest predictive value. In the present study, we have examined ER status by both immunocytochemical assay (ER-ICA) on a fine needle aspirate and by radioligand-binding assay (DCC) on an excised portion of tumour. There was a correlation between the ER level detected by the two assays (Spearman's r = 0.77 for DCC versus ER-ICA staining intensity, r = 0.70 for DCC versus ER-ICA percentage of cells stained, P < 0.0001, n = 137 in each case). Each assay showed an increasing proportion of ER+ve results with increasing patient age. In the case of ER+ve tissues only, while ER concentration by DCC assay increased steadily with age (r = 0.39, P < 0.0001, n = 108), the ER ICA assay revealed that, staining intensity increased with age (r = 0.26, P = 0.001, n = 149) but the percentage of cells stained did not (r = 0.08, P = NS, n = 149). It is concluded that increasing endocrine responsiveness with advancing age could reflect the increasing proportion of ER+ve tumours with increased levels of ER per cell (as indicated by staining intensity) rather than increasing proportion of ER+ve cells. PMID- 1419598 TI - Influence of tumour physico-chemical conditions on interleukin-2-stimulated lymphocyte proliferation. AB - The proliferative response of murine lymphocytes to interleukin-2 (IL-2) was examined under physico-chemical conditions present in solid tumours, namely low oxygen and glucose concentrations and acidic pH. Lymphocytes were cultured for four days in 30 U ml-1 IL-2 to simulate serum IL-2 concentrations attainable with high-dose systemic IL-2 therapy. Lymphocyte proliferation was significantly (P < 0.05) reduced by low oxygen concentrations (both anoxia [0% O2] and hypoxia [10%, low glucose (6 mg dl-1), or acidic pH (6.7 or 6.4). Moderate glucose concentration (32 mg dl-1), or neutral pH (7.0) did not impair proliferation. This study indicates that impairment of lymphocyte proliferation by tumour physico-chemical conditions may be a factor in the relatively poor success rate of IL-2/LAK cell immunotherapy. PMID- 1419597 TI - Active melanogenesis in non-S phase melanocytes in B16 melanomas in vivo investigated by double-tracer microautoradiography with 18F-fluorodopa and 3H thymidine. AB - 3,4-Dihydroxy-2-[18F]fluoro-L-phenylalanine (2-[18F]FDOPA) and [6-3H]thymidine ([3H]Thd) were simultaneously injected into mice transplanted with B16 melanomas of FM3A mammary carcinoma. Melanogenesis was differentiated from DNA synthesis in the mitotic cell cycle by monitoring grain distribution with double-tracer microautoradiography. The percentages of pigmented cells were inversely proportional to those of [3H]Thd-labelled cells, indicating that the greater the number of melanocytes, the smaller was the number of proliferating cells. The number of grains produced by 2-[18F]FDOPA in the [3H]Thd-unlabelled melanocytes was significantly higher (P < 0.001) than the numbers in the [3H]Thd-labelled melanocytes and in nonmelanocytes. The [3H]Thd-unlabelled non-melanocytes and FM3A cells showed the lowest accumulation of 2-[18F]DOPA, which may have resulted from the basic amino acid demand by malignant neoplasms via amino acid transport. The [3H]Thd-labelled cells, regardless of whether they were pigmented or not, had slightly more grains with 2-[18F]FDOPA than the [3H]Thd-unlabelled non melanocytes (P < 0.05), which may have resulted from the enhanced amino acid requirement for proliferation. Melanogenesis appeared to be activated only in the non-S phase of the mitotic cycle in melanocytes. PMID- 1419599 TI - Malignant progression of a mouse fibrosarcoma by host cells reactive to a foreign body (gelatin sponge). AB - The QR regressor tumour (QR-32), a fibrosarcoma which is unable to grow progressively in normal syngeneic C57BL/6 mice, was able to grow progressively in 13 out of 22 mice (59%) when it was subcutaneously coimplanted with gelatin sponge. We established four culture tumour lines from the resultant tumours (QRsP tumour lines). These QRsP tumour lines were able to grow progressively in mice even in the absence of gelatin sponge. The ability of QRsP tumour cells to colonise the lungs after intravenous injection and to produce high amounts of prostaglandin E2 (PGE2) during in vitro cell culture was much greater than that of parent QR-32 cells. These biological characteristics of QR-32 cells and QRsP tumour cells were found to be stable for at least 6 months when they were maintained in culture. We also observed that QR-32 cells were able to grow progressively in five out of 12 (42%) mice after coimplantation with plastic non adherent peritoneal cells obtained from mice which had been intraperitoneally implanted with gelatin sponge. These host cells reactive to gelatin sponge increased the production of high amounts of PGE2 by QR-32 cells during 48 h coculture. Preliminary in vitro studies implicated the involvement of hydrogen peroxide and hydroxyl radical as some of the factors necessary to induce QR-32 cells to produce high amounts of PGE2 and to accelerate tumour progression. PMID- 1419601 TI - p53 expression in Reed-Sternberg cells of Hodgkin's disease. AB - Mutation of the p53 protein may represent the commonest genetic event in human malignancy. Abnormal p53 expression has been reported in a variety of carcinomas, sarcomas and lymphoid neoplasms; however there is little information in relation to Hodgkin's disease. The expression of the nuclear phosphoprotein was investigated in paraffin-embedded biopsies from fifty patients with Hodgkin's disease using a polyclonal antibody, CM-1 and in snap-frozen material with monoclonal antibodies, PAb 1801 and PAb 240. Specifically, immunoreactivity was localised to the Reed-Sternberg cells or mononuclear variants in both nodular sclerosing (86% cases) and mixed cellularity (57% cases) subtypes of Hodgkin's disease. However, no positive staining was found in our cases of nodular lymphocyte predominant type Hodgkin's disease. Serial biopsies following recurrence of disease demonstrated consistent results. It is suggested that overexpression of p53, probably mutant, may have a role in the tumorigenesis of Hodgkin's disease. PMID- 1419600 TI - Modulation of the proliferative response of breast cancer cells to growth factors by oestrogen. AB - A number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol. MCF-7 cells were treated with growth factors in the presence and absence of oestradiol. Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and basic fibroblast growth factor (bFGF). Platelet derived growth factor (PDGF) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-beta slightly reduced the stimulation by oestradiol. In the absence of oestradiol, there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive. In the presence of oestradiol, the effects of bFGF and TGF-alpha were additive whereas bFGF acted as an IGF-I antagonist. Overall, bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin. The effects of oestradiol on the sensitivity of cells to the proliferative effects of bFGF did not appear to result from regulation of bFGF receptor expression. PMID- 1419602 TI - Induction of HSP70 is associated with vincristine resistance in heat-shocked 9L rat brain tumour cells. AB - The most prominent cellular changes in heat-shock response are induction of HSPs synthesis and reorganisation of cytoskeleton. Vincristine was used as a tool to evaluate the integrity of microtubules in 9L rat brain tumour cells recovering from heat-shock treatment. Cells treated at 45 degrees C for 15 min and recovered under normal growing condition became resistant to vincristine-inflicted cytotoxicity and microtubule destruction. Among all HSPs, the level of HSP70 and the degree of vincristine resistance are best correlated. HSP70 and tubulin were found to be associated with each other as they were co-immunoprecipitated by either anti-HSP70 or anti-beta-tubulin monoclonal antibody. The current studies establish for the first time that HSP70 can complex with tubulin in cells and this association may stabilise the organisation of microtubules thus protect the heat-treated cells from vincristine damage. These findings are noteworthy in combining hyperthermia and chemotherapy in the management of malignant diseases. PMID- 1419603 TI - Growth, morphology and chemosensitivity studies on postconfluent cells cultured in 'V'-bottomed microtiter plates. AB - This study assessed the growth pattern, cellular organisation and chemosensitivity of established human tumour cell lines growing as postconfluent cultures in 'V'-bottomed, 96-well microtiter plates. Cross-sections of the colon (HT29, SW620, SW1116), ovarian (A2780) and head and neck (UM-SCC-22B) carcinoma microcultures allowed in situ evaluation of the cellular organisation in the wells. After 5 days of growth, every cell line had reached confluence, but each of them displayed a specific pattern of cell stacking which ranged from two to ten layers. Postconfluent HT29 cells displayed morphologic features suggestive of some degree of enterocytic differentiation. Growth and cytotoxicity could be studied reliably and reproducibly in this system with the sulforhodamine B protein assay. Against HT29 postconfluent cultures, the EC50's (drug concentrations producing absorbance readings 50% lower than those of non-treated wells) of 5-fluorouracil and of the ether lipid, hexadecylphosphocholine, were 1 mM and 50 microM respectively. The possibility to perform chemosensitivity tests using semiautomated microtiter plate technology supports further evaluation of this system as an alternative antitumour drug testing model. PMID- 1419604 TI - No effect of dose, hepatic function, or nutritional status on 5-FU clearance following continuous (5-day), 5-FU infusion. AB - One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5 day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875.5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5 FU Cl, ml min-1 m-2 = 791-7769, mean 2820.7). Log 5-FU Cl was not modified by 5 FU dose (r = -0.1034, P = 0.124, n = 222). Poor linear correlations between log 5 FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST:0.0526, 0.4365; Log ALT: -0.1167, 0.0842; Log A1K. Phos.:0.154, 0.0214; Log GGT: 0.0652, 0.3436; Log LDH: -0.0984, 0.1563; Log bilirubin: 0.1278, 0.0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0.0110, 0.8714; prealbumin: -0.1067, 0.1129; transferrin: 0.0439, 0.5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition. PMID- 1419605 TI - Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. AB - A cohort of 11,580 residents of a retirement community initially free from cancer were followed from 1981 to 1989. A total of 1,335 incident cancer cases were diagnosed during the period. Relative risks of cancer were calculated for baseline consumption of vegetables, fruits, beta-carotene, dietary vitamin C, and vitamin supplements. After adjustment for age and smoking, no evidence of a protective effect was found for any of the dietary variables in men. However, an inverse association was observed between vitamin C supplement use and bladder cancer risk. In women, reduced cancer risks of all sites combined and of the colon were noted for combined intake of all vegetables and fruits, fruit intake alone, and dietary vitamin C. Supplemental use of vitamins A and C showed a protective effect on colon cancer risk in women. There was some suggestion that beta-carotene intake and supplemental use of vitamin A, C, and E were associated with reduced risk of lung cancer in women, but none of these results were statistically significant. These inverse associations observed in women seem to warrant further investigation, although there was inconsistency in results between the sexes. PMID- 1419606 TI - Contribution of 3H-thymidine labelling index and flow cytometric S-phase in predicting survival of patients with non-Hodgkin's lymphoma. AB - The 3H-thymidine labelling index (3H-dT LI) of cell suspensions from fresh material and the flow cytometric S-phase (FCM-S) of nuclei recovered from paraffin blocks were determined on the same pathologic lymph node specimen for 190 non-Hodgkin's lymphomas (NHLs). FCM-S was defined by a planimetric method and by an optimization procedure. Poor correlation coefficients were observed among the three cell kinetic variables. All three cell kinetic variables were significant indicators of 8-year survival and median survival time. The life regression procedure evidenced a significant relative contribution of 3H-dT LI and FCM-S, thus suggesting a different biologic meaning of the two cell kinetic variables. This finding was further supported by evidence that simultaneous use of 3H-dT LI and FCM-S can identify groups of patients with different survival better than when either modality is used alone. Multivariate analysis indicated that the risk groups as defined by cell kinetic variables are predictors of survival even in the presence of established factors such as histology and stage. PMID- 1419607 TI - Sarcomas in north west England: III. Survival. AB - Survival data on a population-based series of bone, soft tissue and visceral sarcomas diagnosed in the North West of England between 1982-84 and subjected to histopathological peer review are presented. Five-year crude survival for all cases was 34%. Survival in males and females did not differ significantly (P = 0.6, 5-year survival 32% vs 36%) but was markedly worse for patients diagnosed over the median age of 60 years, even when allowance was made for underlying mortality (P = 0.03, 34% vs 44%). Five-year survival rates for the major site groups were: bone 44%; soft tissues of head, neck and trunk 36%; soft tissues of extremities 35%; female genital tract 35%; retroperitoneum 15%; gastro-intestinal tract 13%. Analysis by the major histological types revealed the following survival rates: leiomyosarcoma--female genital tract 25%, gastro-intestinal tract 14%, non-visceral soft tissue 21%; malignant fibrous histiocytoma of soft tissue 29%; liposarcoma 52%; osteosarcoma of bone 46%; and chondrosarcoma of bone 50%. PMID- 1419608 TI - The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer. AB - The influence of the prototype aromatase inhibitor Aminoglutethimide (AG) and its analogue Rogletimide (RG) on peripheral aromatisation were investigated in 13 postmenopausal women with advanced breast cancer. Seven patients received AG 1,000 mg daily plus Hydrocortisone (HC) cover and six received RG as dose escalation of 200 mg bd, 400 mg bd and 800 mg bd. In vivo aromatase inhibition was investigated using the double bolus injection technique with [4-14C] oestrone ([4-14C]E1) and [6,7-3H] androstenedione ([6,7-3H]4A) followed by a 96 h urine collection. The labelled urinary oestrogens were separated and purified by chromatography and HPLC. Plasma oestradiol (E2) was also measured. AG mean aromatase inhibition was 90.6% +/- 1.8 s.e.m. and E2 suppression 75.7% +/- 7.3 s.e.m. RG mean aromatase inhibition was 50.6% +/- 9.8 s.e.m. at 200 mg bd, 63.5% +/- 5.7 s.e.m. at 400 mg bd and 73.8% +/- 5.8 s.e.m. at 800 mg bd. E2 suppression was 30.7% +/- 9.5 s.e.m., 40.2% +/- 10.3 s.e.m. and 57.6% +/- 9.2 s.e.m. respectively. These results confirm the efficacy of AG as an aromatase inhibitor. RG produced dose dependent E2 suppression and aromatase inhibition, but even at the maximum tolerated dose of 800 mg bd had sub-optimal aromatase inhibition and oestradiol suppression compared with AG. PMID- 1419609 TI - Lobular panniculitis after subcutaneous administration of interleukin-2 (IL-2), and its exacerbation during intravenous therapy with IL-2. AB - Interleukin-2 (IL-2) is now registered for the treatment of renal cell carcinoma in a number of European countries. The subcutaneous (sc) route of administration is being used increasingly because of its better toxicity profile compared with higher dose intravenous (iv) protocols. We report here a patient who developed a lobular panniculitis at the site of sc IL-2 injection which prevents continuation of sc therapy. Subsequent administration of the same IL-2 dose by iv injection caused recurrence of the problem again necessitating discontinuation of IL-2 treatment. PMID- 1419610 TI - Lung cancer and passive smoking: reconciling the biochemical and epidemiological approaches. AB - The accurate determination of exposure to environmental tobacco smoke is notoriously difficult. There have been to date two approaches to determining this exposure in the study of association of passive smoking and lung cancer: the biochemical approach, using cotinine in the main as a marker, and the epidemiological approach. Typically results of the former have yielded much lower relative risk than the latter, and have tended to be ignored in favour of the latter, although there has been considerable debate as to the logical basis for this. We settle this question by showing that, using the epidemiologically based meta-analysis technique of Wald et al. (1986), and misclassification models in the EPA Draft Review (1990), one arrives using all current studies at a result which is virtually identical with the biochemically-based conclusions of Darby and Pike (1988) or Repace and Lowry (1990). The conduct of this meta-analysis itself raises a number of important methodological questions, including the validity of inclusion of studies, the use of estimates adjusted for covariates, and the statistical significance of estimates based on meta-analysis of the epidemiological data. The best estimate of relative risk from spousal smoking is shown to be approximately 1.05-1.10, based on either of these approaches; but it is suggested that considerable extra work is needed to establish whether this is significantly raised. PMID- 1419611 TI - Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients. AB - Tumours from 336 breast cancer patients under the age of 50 were analysed for hormone receptor content and by DNA flow cytometry. Sixty-six percent of the tumours were positive for estrogen receptors (ER), 60% were progesterone receptor (PR) positive and 42% showed DNA diploid profiles. DNA hypodiploid tumours were relatively frequent (7%), especially in patients aged 40 years or less (11%). S phase fraction (SPF), with a mean of 10%, correlated significantly with receptor status, DNA ploidy, lymph node status, tumour size and age. With a median follow up period of 34 months, the distant recurrence-free interval was independently predicted by lymph node status, tumour size, SPF and PR content. Amongst the 212 patients who had not received adjuvant systemic treatment, receptor status was, in addition to lymph node status and SPF, independently related to distant recurrence rate. A high SPF identified a subgroup with high recurrence rate, comprising approximately one third of the node-negative patients. Similarly, the one third of node-positive patients who had PR-positive tumours with a low S phase fraction formed a subgroup with low recurrence rate. We conclude that hormone receptor assays and DNA flow cytometry should be useful tools in the management of breast cancer patients less than 50 years of age. PMID- 1419612 TI - Interleukin-4 receptor and epidermal growth factor receptor expression in colorectal cancer. AB - Interleukin-4 receptor (IL-4R) and Epidermal Growth Factor receptor (EGFR) were assessed as factors associated with adenoma-carcinoma progression in colorectal cancer and tumour invasion. A monoclonal antibody (MR6) was applied to detect IL 4R in: metaplastic polyps (five cases), adenomas (15 cases), and carcinomas (44 adenocarcinomas and one squamous cell). Positive labelling was obtained in all polyps, adenomas and in 40/45 carcinomas. Normal colonic mucosa of these patients, as well as macrophages and lymphocytes infiltrating the tumour stroma, were also positively labelled with MR6. Four out of five poorly differentiated adenocarcinomas did not show IL-4 receptor expression. No significant correlation was found with tumour size, lymph node stage and IL-4 receptor expression. On the above specimens a parallel detection of epidermal growth factor receptors (EGFR) by a monoclonal antibody (EGFR 1) was carried out. Expression of EGFR was found in 14/20 polyps and in 22/45 carcinomas. All but one of the EGFR positive malignant tumours showed coexpression of IL-4 receptor. Lymph node involvement by tumour cells was detected in 25 out of 45 patients. Eighteen of these 25 cases were positive with EGFR1. PMID- 1419613 TI - Single agent high-dose cisplatin (200 mg m-2) treatment in ovarian carcinoma. AB - Twenty patients with epithelial ovarian carcinoma were treated with high-dose cisplatin 200mg m-2. Patients were to receive three cycles at 21 day intervals. Treatment was stopped if severe myelosuppression or any neurotoxicity occurred. Overall, eight (40%) of patients responded with a complete response in five (25%). Four of 16 (25%) previously treated patients responded. The median duration of response was 44 weeks (range 6-130). In patients previously treated there was a significant association (P < 0.002) between response and a remission free interval of 52 weeks or more from primary chemotherapy. Toxicity was assessable in 18 patients. Alopecia and nausea/vomiting were common. Myelosuppression was recorded in nine patients delaying planned administration in eight of 35 cycles. Five patients developed anaemia and six thrombocytopenia. Neurotoxicity affected seven patients and varying degrees of tinnitus six patients. Neurotoxicity and myelosuppression were indications for cessation of treatment in 8 patients receiving less than three cycles. Analysis revealed no significant association between toxicity and prior cisplatin exposure, age or the amount of high-dose cisplatin administered. This series reveals that it is possible to achieve good response rates using high-dose cisplatin without encountering debilitating neurotoxicity. PMID- 1419614 TI - Trends in endometrial cancer incidence and survival in the Swiss Canton of Vaud. PMID- 1419615 TI - Flavone acetic acid (FAA) with recombinant interleukin-2 (TIL-2) in advanced malignant melanoma. II: Induction of nitric oxide production. AB - Plasma samples were collected from 20 patients undergoing phase I clinical trial with flavone-8-acetic acid (FAA; 4.8 g m-2 per dose) in combination with recombinant human interleukin-2 (rhIL-2; 6-18 i.u. m-2 per day) for the treatment of metastatic melanoma. Samples were analysed for nitrate content as an indication of the oxidation of L-arginine to nitric oxide. Pretreatment plasma nitrate levels (53 +/- 4 microM) were significantly above those of healthy volunteers (19 +/- 4 microM). The maximum plasma nitrate concentration obtained after treatment, 190 +/- 29 microM (range 49 to 655 microM), was comparable to that of mice treated with FAA. Most of the increases occurred 3-5 days after initiation of a 5 day infusion of rhIL-2, but three of the increases occurred within 2 days of a 1 h infusion of FAA alone. The maximum plasma nitrate concentrations of the three patients which underwent remission (two complete, one partial) following treatment (368 +/- 143 microM) were significantly higher (P < 0.05) than those of patients with progressive disease. Hypotension was the major dose-limiting side effect, and there was no relationship between the degree of hypotension and the rise in plasma nitrate. The results provide evidence that treatment of patients with FAA and rhIL-2 induce the synthesis of nitric oxide, a physiological mediator and potential cytotoxic agent. PMID- 1419616 TI - Haemostatic changes and thromboembolic risk during tamoxifen therapy in normal women. AB - Tamoxifen has been implicated as a risk factor for venous thrombosis in advanced breast cancer although the evidence for increased arterial or venous thrombosis with tamoxifen in early breast cancer is less clear. The effect of tamoxifen on haemostasis, and thereby possible thromboembolic risk, was investigated in normal women enrolled in a placebo controlled trial of tamoxifen as a chemopreventative agent for breast cancer. There was an initial reduction in fibrinogen levels in all women on tamoxifen over the first year of follow-up and a marginal reduction in antithrombin III and Protein S in postmenopausal women at 6 months. There were no changes in cross linked fibrinogen degradation products or Protein C for pre or post-menopausal women. There was no increase in the incidence of thromboembolic events on tamoxifen. This study demonstrates that tamoxifen has only marginal effects on factors involved in haemostasis reported to affect the incidence of arterial or venous thromboembolic disease. The follow-up time is relatively short (maximum 36 months) and careful long term follow-up is necessary to detect clinically significant morbidity. PMID- 1419617 TI - The adenoma-carcinoma sequence in the colorectum--early appearance of a hierarchy of small intestinal mucin antigen (SIMA) epitopes and correlation with malignant potential. AB - The colorectal adenoma-carcinoma sequence was examined in relation to the ectopic expression of the oncofoetal Small Intestinal Mucin Antigen (SIMA), to the development of morphologic changes in the adenoma and perineoplastic mucosa and to indices of malignant potential. Four anti-SIMA MAbs, which define a novel hierarchy of SIMA epitopes in the normal small intestine and adjacent to colorectal cancers, were used in a retrospective immunohistochemical study of Familial Adenomatous Polyposis (FAP, n = 183) and non-familial (n = 44) adenomas. Inappropriate expression of SIMA epitopes was first detected in mucosa adjacent to minute microadenomas larger than three glands, and with increase in size, in increasing amounts within adenomas themselves, but not with microadenomas smaller than three glands or regions of flat mucosa free of adenomas. SIMA epitope expressed in mucosa adjacent to adenomas preceded changes in perineoplastic morphology, which progressed with adenoma growth to resemble transitional mucosa (TM) adjacent to cancers. Thus, the onset of both SIMA expression and morphological changes in TM were consistent with reactive rather than pre existing field change phenomena. The previously reported hierarchy of four SIMA epitopes (5C5, 3D4, 4D3, 6C5) was also consistently observed in the adenoma carcinoma sequence, and applied to (i) the order of epitope detection, (ii) the number of positive adenomas and (iii) extent of staining; (iv) the height in the crypt and (v) distance from the adenoma to which epitopes were expressed in perineoplastic mucosa. These observations are consistent with a progression of changes in mucin composition with adenoma development. The percentage of positive adenomas and reactivity scores for each anti-SIMA MAb correlated with increasing adenoma size, degree of dysplasia and growth pattern. SIMA expression appears to predate the earliest reported oncogene and tumour suppressor gene changes, was persistent and increased throughout adenoma development. SIMA epitopes are thus markers of very early neoplastic change, whose expression correlates with malignant potential and may contribute to the accumulation of changes necessary for tumourigenesis. PMID- 1419618 TI - Increased p53 protein content of colorectal tumours correlates with poor survival. AB - Allelic losses on the short arm of chromosome 17 occur frequently in colorectal cancers. Despite the existence of other common molecular events such as loss of the long arms of chromosomes 18 and 5, it has been demonstrated that the former has the greatest prognostic significance. Of the various genes mapping to the commonly deleted sequence, the best candidate as a 'target' seems to be the p53 antioncogene. We applied our methods of detection of the p53 protein in a series of 78 colorectal cancers stored in a tumour bank from 1985 to 1989, for which the median follow-up was 42 months. Nuclear-attached p53 was quantified by flow cytometry and soluble p53 was assayed by ELISA. Both assays used a monoclonal antibody considered to be specific for a conformational epitope present only on the mutated protein. Fifty of the 78 tumours (64%) were found to present significant levels of p53 attached to the nucleus. A further two tumours contained high levels of p53 only in their soluble fraction. Thus, 52 out of 78 cancers (67%) were considered to be positive for p53. The p53 content correlated with 17p loss (P < 0.002), hyperdiploid DNA content (P < 0.001) and tumour site (P < 0.03), but not Dukes' stage (P = 0.15). p53 negative cases had a better overall survival than p53 positive ones (P < 0.03). When the 14 stage D tumours were excluded from the analysis, p53 was no longer significantly predictive of survival (P < 0.07), but remained predictive of recurrence (P < 0.02) and metastasis (P < 0.03). Multivariate analysis was not performed because of the small number of cases. Overall, disease-free and metastasis-free survival were compared to the positivity obtained either with pAb 421 and/or 1801 or pAb 240 since all three were used in the flow cytometric analysis, defining subsets of 421-, 1801+ and 421-, 1801-, 240+. The presence of nuclear protein presenting the mutation-specific epitope, recognised by pAb 240, was found to be the most discriminant. It must be noted that univariate survival analysis demonstrated that more than 80% of patients with p53-negative tumours were alive at 3 years vs less than 50% in the p53-positive group. A large prospective study should be conducted to define the exact prognostic significance of the p53 content of colorectal carcinomas. PMID- 1419619 TI - Clinical pharmacokinetics of epirubicin: the importance of liver biochemistry tests. AB - The influence of liver biochemistry tests on epirubicin pharmacokinetics has been investigated in 52 women with advanced breast cancer, 27 of whom had radiologically proven liver metastases. Patients received epirubicin 12.5-120 mg m-2 given as an i.v. bolus. Epirubicin levels were measured by HPLC following the first cycle of treatment. Epirubicin elimination, expressed as clearance (dose/AUC), in the 22 patients with normal AST and bilirubin was compared with that of 30 patients with a raised AST +/- raised bilirubin. Epirubicin clearance was significantly reduced in the patients with a raised AST, whether their serum bilirubin was normal (22 patients) or elevated (eight patients). In the 30 patients with a raised AST +/- raised bilirubin, epirubicin clearance correlated strongly with the level of AST (r = -0.72) but not with serum bilirubin, alkaline phosphatase, albumin or creatinine. Using a multiple regression analysis, AST was the only one of these biochemical variables predictive of epirubicin clearance (r2 = 0.47, P = 0.0006). We conclude that a raised serum AST is a more sensitive and reliable measure of abnormal epirubicin pharmacokinetics than increased bilirubin. These findings have implications for anthracycline treatment in patients with abnormal liver biochemistry. PMID- 1419620 TI - Prognostic factors in breast cancer. PMID- 1419621 TI - Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH 130). AB - The metabolism of cholesterol has been investigated in tumour cells, ascitic fluid and blood serum during the growth of an ascites hepatoma (Yoshida AH-130) in the rat. High rates of cholesterol synthesis and elevated free and esterified cholesterol content were observed in tumour cells. During tumour growth, the host animals progressively developed marked changes in the level and distribution of serum cholesterol consisting in an increase of total cholesterol and of a marked reduction of HDL cholesterol (HDL2 subfraction in particular). In agreement with previous observations, these findings indicate that a consistent pattern of altered cholesterol homeostasis develops in relation to normal or neoplastic tissue growth. High synthetic rates and intracellular accumulation of cholesterol are observed in the proliferating cells. Moreover, blood serum cholesterol decreases in the HDL fraction while it increases in LDLs, suggesting that during proliferative processes cholesterol fluxes between tissues and serum lipoproteins are markedly perturbed. PMID- 1419622 TI - Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay. AB - A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5 FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response). PMID- 1419623 TI - Treatment with a non-steroidal anti-inflammatory agent delays the growth of spontaneous pulmonary metastases of a mammary adenocarcinoma of non-detected immunogenicity. AB - Previous reports showed that treatment with non-steroidal anti-inflammatory agents (NSAIA) can alter the growth profile of a variety of tumours. In this study, the effect of NSAIA treatment on the growth of the primary tumour and the appearance of spontaneous pulmonary metastases, was investigated. A mammary adenocarcinoma of non-detected immunogenicity, C7HI, was grafted subcutaneously in the lateral flank of Balb/c mice. Oral treatment with approximately 1 mg kg-1 day-1 piroxicam delayed both tumour growth and the growth of pulmonary metastases. Survival of mice bearing the primary tumour was significantly lengthened by anti-inflammatory treatment. Similarly, in separate experiments, after surgical removal of the primary tumour by day 34 after grafting, the group of mice treated orally with piroxicam also exhibited a higher survival rate than the control group. Upon surgical removal of the primary tumour 34 days after grafting, piroxicam treatment significantly decreased both the number and size of pulmonary metastases. The results of this study lends support to the hypothesis that inhibition or modulation of inflammation may delay tumour organisation and growth. It is suggested that piroxicam treatment may be an appropriate adjunct therapy to delay the appearance of pulmonary metastases and to increase life expectancy in a host whose primary tumour has to be surgically removed. PMID- 1419624 TI - The detection of specific gene rearrangements in non-Hodgkin's lymphoma using the polymerase chain reaction. AB - Characteristic gene rearrangements are present in most non-Hodgkin's lymphomas (NHL). These are usually detected by Southern blotting techniques. In this study, the ability of the polymerase chain reaction (PCR) to detect the t(14;18) chromosomal translocation and immunoglobulin heavy chain (IgH) gene rearrangement was evaluated. DNA from 14 follicular and 42 diffuse B-cell lymphomas was examined using oligonucleotide primers specific for opposing sides of the IgH gene rearrangement on chromosome 14 (towards conserved VH and JH sequences) and opposing sides of the t(14;18) chromosomal translocation (towards the major breakpoint region of the bcl-2 gene on chromosome 18 and conserved JH sequence on chromosome 14). The t(14;18) translocation was detected in 57% of follicular lymphomas and 21% of diffuse B-cell lymphomas. Clonal IgH gene rearrangements using PCR were detected in 50% follicular and 52% of the diffuse lymphomas. Either or both of these rearrangements were detected in 93% follicular and in 59% of diffuse lymphomas. PCR is a rapid and easy technique that can detect the abnormal rearrangement of the bcl-2 gene and clonal IgH rearrangement, indicating the presence of lymphoma. This may be of benefit in monitoring response to therapy and in predicting prognosis in this disease. PMID- 1419625 TI - Potent antitumour activity of (-)-(R)-2-aminomethylpyrrolidine (1,1 cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) against advanced L1210 leukaemia in mice. AB - The time dependency of the antitumour activity of (-)-(R)-2 aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R) was examined in mice inoculated i.p. with 10(5) mouse L1210 leukaemia cells. The increase in life span was greater in mice treated with 72 mg kg-1 DWA2114R on the 6th day following tumour inoculation than in mice treated at earlier times. Such superior effects against advanced L1210 were also seen with cis-diammine (1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) but not seen with the parent compound, cis-diamminedichloroplatinum(II) (CDDP) or other antitumour agents devoid of platinum. After the injection of DWA2114R on day 6, most of the ascites tumour cells accumulated in the S and G2/M phases of the cell cycle and the total cell number markedly decreased from 10(8) to less than 10(6). On the other hand, only a temporary G1 arrest and a less than 50% reduction of the cell number were induced after a similar treatment on day 3. Interestingly, the superiority of DWA2114R for advanced L1210 was lost in athymic nude mice and mice depleted of T cells by anti-thymocyte antisera. In addition, mice cured of advanced L1210 specifically rejected re-inoculated L1210 cells. These results indicate that the superior antitumour activity against advanced L1210 is unique to DWA2114R among the agents tested (except for CBDCA) and is caused by both an increased drug susceptibility of tumour cells and a drug-induced antitumour effect mediated by T cells of the host mice. PMID- 1419626 TI - O6-alkylguanine-DNA-alkyltransferase activity and nitrosourea sensitivity in human cancer cell lines. AB - The DNA repair enzyme, O6-alkylguanine-DNA-alkyltransferase (ATase), is thought to be the principal mechanism controlling resistance to nitrosoureas and related alkylating agents. We compared the sensitivities of five human testis and five bladder tumour cell lines to two nitrosoureas (N-nitroso-N-methylurea (MNU) and mitozolomide) with cellular levels of ATase. Enzyme levels ranged from 3 to 206 fmol mg-1 protein (0.1 x 10(4) to 5.1 x 10(4) molecules/cell) in the testis lines and from 11 to 603 fmol mg-1 (0.4 x 10(4) to 9.1 x 10(4) molecules/cell) in the bladder lines. Based on IC50s in an MTT assay, the testis tumour cell lines were, on average, four times more sensitive to MNU and six times more sensitive to mitozolomide than the bladder cell lines. The cytotoxicities of MNU and mitozolomide were closely related (R = 0.9). In the testis cell lines ATase activity (molecules/cell) was related to IC50s for mitozolomide (R = 0.97) but not MNU (R = 0.78). In the bladder cell lines and overall, ATase activity correlated with cellular sensitivity to neither agent. Relatively high levels of resistance occurred in cells expressing low levels of ATase, and amongst cell lines expressing high levels of ATase, large differences in IC50s were observed. These results support the suggestion that resistance to nitrosoureas can be mediated by mechanisms other than ATase and that at relatively high levels of expression, ATase does not confer resistance in proportion to its activity. PMID- 1419627 TI - The prognosis of primary and metastasising melanoma. An evaluation of the TNM classification in 2,495 patients. AB - The prognostic value of the TNM classifications of the UICC dated 1978 and 1987, was investigated in a population of 2,495 patients who were followed up over the long term. In the case of primary melanoma, Breslow's tumour thickness proved to be the most powerful predictor of patient survival in multivariate analysis, while the significance of Clark's level ranged after that of both localisation of the primary tumour and the sex of the patient. The continuous proportional relationship between tumour thickness and risk of death makes it possible to regrade thickness groups. Grading cutoffs at 1, 2 and 4 millimetres, with no account being taken of depth of invasion, proved to be particularly favourable for a classification in accordance with prognostic criteria. In advanced stages of the disease, the outcome of locoregional and distant metastasis is significantly different; and furthermore in the case of locoregional metastasis, in-transit and satellite metastases exert a significantly better prognosis than regional lymph node involvement. Isolated juxtaregional lymph node metastases occurred primarily or during the course of the observation period in only 19 patients of our group, and, in comparison with visceral metastases, proved to have only an insignificantly better prognosis. For this reason, it would appear meaningful to assign them to a common stage. On the basis of these results, proposals are made for modifications of the TNM classification. PMID- 1419628 TI - Anticipatory nausea and emesis, and psychological morbidity: assessment of prevalence among out-patients on mild to moderate chemotherapy regimens. AB - The prevalence of nausea and emesis among a series of out-patients (n = 95) receiving mainly mild-to moderately-emetic cytotoxics, was assessed, along with levels of psychological morbidity. Particular focus was given to the rates of psychologically-based (anticipatory) nausea and emesis. Results indicated that 23% of patients experienced anticipatory nausea and the majority reported that this occurred before at least half of the previous treatment cycles. Both emetic challenge of chemotherapy regimen and younger age were linked to this anticipatory effect. The data clearly indicated that nausea and emesis, both post treatment and in anticipation of treatment, carried a psychological cost with anxiety being highest in those experiencing anticipatory nausea and/or emesis. The role of anxiety in the aetiology of psychologically-based nausea and emesis was not evaluated and it is considered that a prospective study is needed to clarify the exact contribution of psychological factors in the incidence of both post-treatment and anticipatory side-effects. PMID- 1419629 TI - The expression of 5T4 antigen in colorectal and gastric carcinoma. AB - The expression of 5T4, an oncotrophoblast cell surface antigen was examined in 72 colorectal and 27 gastric carcinomas, with immunoperoxidase technique, on frozen sections. Highly significant association was found between 5T4 expression in the malignant cells and metastatic spread. The results suggest that the appearance of 5T4 molecules in cancer cells reflects a change which may contribute to the development of metastatic potential. PMID- 1419630 TI - The influence of the host on the course of gastric carcinoma. AB - Immunoglobulins (Ig) and some complement components (C) were quantified in sera from patients with gastric carcinoma before surgery and at regular intervals during a 5-year follow-up. The preoperative concentrations of C1-INH and C4 were higher (P < 0.0005 and P < 0.005) and IgG lower (P < 0.0005) in 50 patients with recurrence than in 46 5-year survivors. The prognostic significant of C1-INH was superior to that of the extent of disease (F-values 37.1 and 26.1). The preoperative immune data classified 76% of the patients correctly as to recurrence and no recurrence. Also, the preoperative C1-INH concentration had a highly significant effect on time to recurrence of cancer (P = 0.0007), adjusting for age and disease extent. After surgery the mean IgG concentrations were within normal range and without difference between the two groups. On the other hand, the concentrations of C1-INH and C4 in the individual patients in both groups remained the same from before to after surgery and throughout the observation period (P = 0.34). Apparently, the serum levels of C1-INH and C4 do not reflect the bearing of cancer. We therefore suggest that these variables represent an independent immune state that is appropriate to the host. A comparison of our variables with those of healthy individuals seems to support this idea. This immune state has a significant influence on whether a resected gastric cancer will recur, and also on how soon recurrence may be manifest. PMID- 1419631 TI - CA-125 is not a useful marker in metastatic breast cancer. PMID- 1419632 TI - Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. AB - In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation. PMID- 1419634 TI - Cancer mortality in African and Caribbean migrants to England and Wales. AB - Cancer mortality during 1970-85 of immigrants from East and West Africa and the Caribbean to England and Wales is described. Overall cancer mortality was raised in West African males (RR 1.38, 95% CI 1.25-1.54), and non-significantly raised in West African females (RR 1.14, 0.96-1.37) compared to mortality in the England and Wales-born population. Much of the increased risk was due to very high rates of liver cancer in males (RR 31.6, 23.8-41.9), but rates were also raised for a wide range of other cancers in each sex. Only lung and brain cancer had significantly decreased mortality. In East Africans, overall cancer mortality was low in males (RR 0.63, 0.56-0.70), and in females (RR 0.80, 0.72-0.89). Mortality was significantly low for cancers of the stomach, pancreas and testis, and Hodgkin's disease in males, for cervical cancer in females, and for lung cancer and melanoma in both sexes. Cancer sites with significantly raised mortality included oropharyngeal cancer, leukaemia, and multiple myeloma in both sexes. In Caribbean immigrants overall cancer rates were significantly low in males (RR 0.71, 0.68-0.74) and in females (RR 0.76, 0.73-0.80). Mortality was significantly low for many cancers including colorectal, lung, testis and brain cancers. Mortality was significantly raised only for cancer of the prostate in males, of the placenta in females, and of the liver, non-Hodgkin's lymphoma and multiple myeloma in both sexes. Overall, mortality was high from prostatic cancer and liver cancer, and was low from brain cancer, in predominantly ethnic African immigrant groups. Both East and West African immigrants had raised rates of leukaemia. All of the migrant groups had high rates of multiple myeloma and low rates of testicular, ovarian and lung cancer. Genetic and environmental factors that may contribute to these patterns are discussed. PMID- 1419633 TI - Increased expression and mutation of p53 in choroidal melanoma. AB - Using CM-1 antibody directed against the human p53 protein, high levels of mutant p53 protein expression were found in 12 out of 18 malignant choroidal melanomas. In contrast, we failed to observe elevated p53 expression, indicating the absence of p53 mutation in seven choroidal naevi, a potentially premalignant condition that can progress to form malignant melanoma. For two choroidal melanomas, we demonstrated that high levels of p53 protein were accompanied by exon 7 mutations. The mutations were found at codon 238, TGT-->TTT and codon 253, ACC- >AGC. These observations suggest that acquisition of abnormalities of the p53 gene may be an important step in the development of malignant melanoma. PMID- 1419636 TI - Breast self examination and survival from breast cancer. AB - The survival of 616 women aged 15-59 with breast cancer, 226 of whom had been taught and practised breast self examination (BSE) prior to diagnosis and 390 of whom had not, is reported. Six year survival rates were 73.1% in the BSE taught group and 66.1% in other women (P = 0.07). PMID- 1419635 TI - The epidemiology of AIDS-associated non-Hodgkin's lymphoma in the World Health Organization European Region. AB - This paper describes the epidemiology of AIDS-associated non-Hodgkin's lymphoma (NHL) in the World Health Organization (WHO) European Region. Data, collected by the WHO Collaborating Centre on AIDS in Paris, France, were derived from the national AIDS surveillance systems of 21 countries. Among 53,042 cases reported as of the end of June 1991, 1,617 (3.0%) had NHL as the presenting clinical manifestation of AIDS. The proportion of cases presenting with NHL ranged from 1.1% in children infected perinatally to 3.9% among haemophiliacs. In comparison with intravenous drug users (IVDUs) (2.6% of whom had NHL), a moderate excess was found among homosexual or bisexual men (odds ratio - OR -:1.2, 95% confidence interval - CI -:1.0-1.3). Over time, the proportion of NHL was constant, but whereas among homosexual or bisexual men the frequency of NHL as AIDS-indicator disease significantly increased (9.7% per year), among IVDUs a significant downward trend emerged (17.1% per year). In respect to age, two peaks of NHL were seen at the age groups 10-19 (3.8%) and 50-59 (4.3%). The proportion of AIDS associated NHL significantly increased with increasing age among homosexual and bisexual men and heterosexuals whereas it decreased among IVDUs. All these differences, however, have to be interpreted cautiously on account of the limitations of the reporting systems. PMID- 1419637 TI - The influence of carbogen breathing on tumour tissue oxygenation in man evaluated by computerised p02 histography. AB - Tumour tissue oxygenation has been measured in man during carbogen breathing (95% O2, 5% CO2) using a commercially available polarographic electrode system (Eppendorf p02 histograph). At least 200 tumour measurements in each of 17 patients with accessible tumours were taken before, and subsequently continuously after the commencement of carbogen breathing for periods of 10 to 30 min. In 12 out of 17 patients studied there was a significant increase in median tumour p02 during the first 10 min of carbogen breathing (range 9 to 1800%). There was an initial rapid increase in tumour p02 which was maintained until 8 to 12 min, but then decreased throughout the subsequent treatment period. Although there was a reduction in the proportion of point measurements < or = 10 mmHg in 11 out of 13 patients, during carbogen breathing, measured points of < or = 2.5 mmHg were only eliminated in three out of 11 tumours. The time course has implications for the planning of clinical trials utilising radiotherapy with carbogen breathing. PMID- 1419638 TI - Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer. AB - DNA Ploidy and S phase fraction (SPF) were measured in Stage I and II breast cancers from patients with at least 8 years of follow-up, to assess the prognostic significance of these data. Disaggregated sections of formalin-fixed, paraffin-embedded tumour were analysed by flow cytometry. SPF was calculated using a rectangular model of S phase, after subtraction of background debris using an exponential model. 64% of tumours were DNA aneuploid. The median SPF was 4.5% for DNA diploid, and 10.9% for DNA aneuploid tumours. There were small reductions in survival at 10 years for DNA aneuploid tumours, and for tumours with above median SPF, but these were not statistically significant. The relative hazard for DNA aneuploid tumours was 1.20 (95% CI 0.81-1.76), and for high SPF was 1.31 (95% CI 0.87-1.98). Neither factor was statistically correlated with survival in multivariate analysis. Technical and theoretical factors limit the accuracy and reproducibility of flow cytometric data, and may explain the lack of prognostic information given. PMID- 1419639 TI - Glutathione S-transferase activity and isoenzyme composition in benign ovarian tumours, untreated malignant ovarian tumours, and malignant ovarian tumours after platinum/cyclophosphamide chemotherapy. AB - Glutathione S-transferase (GST) isoenzyme composition, isoenzyme quantities and enzymatic activity were investigated in benign (n = 4) ovarian tumours and malignant ovarian tumours, before (n = 20) and after (n = 16) chemotherapy. Enzymatic activity of GST in cytosols was measured by determining 1-chloro-2,4 dinitrobenzene conjugation with glutathione, cytosolic GST subunits were determined by wide pore reversed phase HPLC, using a S-hexylglutathione-agarose affinity column, and isoelectric focussing. Both GST activity and GST pi amount were not related to histopathologic type, differentiation grade, or tumour volume index in untreated malignant tumours. GST isoenzyme patterns were identical in benign tumours and malignant tumours before and after platinum/cyclophosphamide chemotherapy, while GST pi was the predominant transferase. Mean GST activity and GST pi amount were decreased (P < 0.05) in malignant ovarian tumours after platinum/cyclophosphamide chemotherapy compared to untreated ovarian malignant tumours. No relation was found in untreated ovarian tumours between GST pi amount and response to platinum/cyclophosphamide chemotherapy. Thus, within the limitations of the current study no arguments were found for a role of GST in in vivo drug resistance of malignant ovarian tumours to platinum/cyclophosphamide chemotherapy. PMID- 1419640 TI - Glutathione S-transferase activity and isoenzyme distribution in ovarian tumour biopsies taken before or after cytotoxic chemotherapy. AB - A study involving the measurement of glutathione S-transferase activities and isoenzyme distributions in human ovarian tumours has been carried out. These tumours have been obtained either at initial debulking surgery, prior to cytotoxic chemotherapy, or at second look laparotomy following chemotherapy. The response rates of these two groups to chemotherapy differ markedly, with patients who have relapsed following initial chemotherapy showing a reduction in response rates to subsequent chemotherapy. Analysis of these data show no statistically significant differences between the glutathione S-transferase activity or isoenzyme distribution in these two groups of patients. Significant differences were observed in the glutathione-S-transferase activities (GST) between tumours and normal ovaries. GST activities in pre-chemotherapy tumours (n = 33, P = 0.01) and post-chemotherapy tumours (n = 20, P = 0.001) where significantly higher than the GST activity in normal ovaries (n = 15). One feature was the expression of the basic isoenzyme which is expressed more in normal ovaries than in tumours. No differences in these parameters were observed in normal peritoneal tissue taken from patients before or after chemotherapy. These data do not support the hypothesis that changes in glutathione S-transferase enzyme activity or isoenzyme expression are major determinants of response to chemotherapy in ovarian tumours. PMID- 1419641 TI - The selection of cases for randomised trials: a registry survey of concurrent trial and non-trial patients. The British Stomach Cancer Group. AB - A randomised trial of adjuvant chemotherapy vs placebo in operable stomach cancer recruited 249 patients from the West Midlands Region between 1976-1980. A Cancer Registry survey identified a further 1261 suitable concurrent cases. Trial patients were compared with the 960 non-trial cases from participating Districts. Only 493 (51%) non-trial cases passed all of the prospective trial selection criteria for entry. Stage and fitness caused the majority of exclusions and were also highly prognostic. A univariate analysis comparing eligible patients with the trial showed the two groups to be balanced for the significant independent prognostic factors of the trial. However, differences in patient age and the surgery performed indicate that recruitment may have been influenced by unknown selection factors. This survey highlights the difficulty of retrospective selection and confirms the need for randomised controls. Data available from specialist Registries may be used to help develop new protocols and to verify and extend trial results. PMID- 1419642 TI - Competing risks determining event-free survival in early breast cancer. AB - To evaluate the natural history of a disease and the effects of therapeutic interventions, it is important to determine which are the causes of treatment failure and to assess the extent to which each cause contributes to the total failure rate. The paper presents a new biostatistical technique to decompose the total event-free survival of a diseased population into cause-specific failure rates. The technique was based on a competing risk approach thereby avoiding biases related to assumptions of independence between different types of event. Such assumptions are inherent in the conventional Kaplan-Meier or actuarial methods. The competing risk method was used to analyse the pattern of failure among 2,850 pre- and postmenopausal patients with early-stage breast cancer and the results were compared to those obtained using conventional methods. The following events were analysed: loco-regional recurrence, distant metastasis, contralateral breast cancer, other new primary malignancies, and intercurrent deaths. The rate of new primary malignancies was found to be significantly higher in post- than in premenopausal patients (6% vs 3% at 10 years). In low-risk, node negative postmenopausal patients the incidence of recurrences from breast cancer were found to be no greater than other types of events. This observation highlights the significance of the effect of different adjuvant therapies not only on the disease itself but also on the risk of second primary malignancies and other intercurrent diseases. In general, it was found that the conventional statistical methods tended to overestimate the event-specific rates. In conclusion, the method based on competing risks permits an unbiased analysis of all types of events determining the total event-free survival. It is thus useful for the description of the natural history of breast cancer as well as other diseases. PMID- 1419643 TI - Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II. AB - Many colorectal liver metastases are hypovascular, and their low level of perfusion is associated with limited drug uptake and poor response rates with regional chemotherapy. We have previously shown that hepatic arterial vasoconstrictors may increase drug delivery to liver tumours, but the underlying haemodynamic changes have not been defined. Using intraoperative laser Doppler flowmetry (LDF) we have assessed the effect of intraarterial angiotensin II (AI) on tumour blood flow in ten patients with colorectal liver metastases. Measurements were performed during placement of infusion catheters for regional chemotherapy. Blood flow was recorded continuously with a Periflux PF3 perfusion monitor via a probe held on the tumour surface, following hepatic arterial infusion of 15 micrograms AII over 90 s. Six patients with isolated small metastases (< 5 cm in diameter) showed increases in flow, which reached a peak at 170-240 s from the start of AII infusion, and which were closely correlated with the corresponding increase in arterial pressure (r = 0.92, P = 0.009). Of the four patients with large confluent tumour deposits, two showed smaller transient increases in flow over the first 60 s of AII infusion and two had no measurable flow response. Increased blood flow following AII infusion may increase the exposure of tumour to therapeutic agents. This study suggests that both tumour size and the effect upon systemic arterial pressure may be important determinants of the blood flow response to AII. LDF may provide useful information about the potential of AII and other vasoconstrictors to enhance targeting precision. PMID- 1419644 TI - Prognostic variables for the selection of patients with operable soft tissue sarcomas to be considered in adjuvant chemotherapy trials. AB - From 1975 to 1988, 144 patients naive of treatment, with non-metastatic soft tissue sarcoma were treated at Fondation Bergonie by surgery, followed by radiotherapy and without chemotherapy. An analysis of prognostic variables was done on this population to determine patients for whom an adjuvant chemotherapy would be relevant. Prognostic variables in overall survival (OS), metastasis-free survival (MFS), disease-free and local free recurrence survivals were analysed by univariate and multivariate analysis. In multivariate analysis using Cox's model, only tumour depth and tumour grade were significant with the MFS end point, while tumour depth, tumour grade and tumour site were significant when considering OS. A predictive stratification for patients is proposed: a favourable prognostic group with grade 1 tumour or superficial, grade 2 tumour (5-year OS: 97.8%; 5 year MFS: 100%); an intermediate prognostic group with deep, grade 2 tumour or superficial, grade 3 tumour (5-year OS: 58.8%; 5-year MFS: 48.1%); and finally a poor prognostic group with deep, grade 3 tumour (5-year OS: 31.7%; 5-year MFS: 34.1%). Patients in the intermediate and poor prognostic groups who present a high metastatic risk are to be considered for adjuvant chemotherapy trials. PMID- 1419645 TI - Value of epidermal growth factor receptor status compared with growth fraction and other factors for prognosis in early breast cancer. AB - The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein whose expression is important in the regulation of breast cancer cell growth. The relationship between EGFR status (determined by an immunocytochemical assay) and various prognostic factors was investigated in 164 primary breast cancers. Overall 56% of tumours were EGFR-positive and the expression of EGFR was unrelated to axillary node status, tumour size and histological grade; and it was poorly associated with the tumour proliferative activity measured by Ki-67 immuno cytochemistry. The relapse-free survival (RFS) probability at 3-years was significantly worse for patients with EGFR positive tumours (P = 0.003) and for those whose Ki-67 score was > 7.5% (P = 0.0027), as well as in patients with axillary node involvement (P = 0.01) and with poorly differentiated tumours (P = 0.04). Immunocytochemical determination of EGFR and cell kinetics gave superimposable prognostic information for predicting RFS with odds ratios of 3.51, when evaluated singly. In our series of patients EGFR, Ki-67 and node status retain their prognostic value concerning RFS in multivariate analysis. The 3-year probability of overall survival (OS) was significantly better in node negative patients (P = 0.04) and was similar in EGFR-positive and negative patients. In conclusion, EGFR status appears to be a significant and independent indicator of recurrence in human breast cancer and the concomitant measurement of the tumour proliferative activity seems to improve the selection of patients with different risks of recurrence. PMID- 1419646 TI - Comparison of plasma prolactin and CEA in monitoring patients with adenocarcinoma of colon and rectum. AB - Plasma prolactin (PRL) and carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 74 patients with adenocarcinoma of colon and rectum. The markers were correlated with disease stage, histological grade and progression/remission of disease. The circulating preoperative median PRL and CEA levels were significantly higher in colorectal cancer patients than in their respective controls. PRL was elevated in all Dukes stages and in all histological grades of the tumour whereas the rise in CEA was more pronounced in Dukes D. Out of 74 patients, 29% (21/74) developed recurrent disease and 31% (23/74) responded to the treatment. With regard to monitoring recurrence(s), the predictive value of PRL was 94% which was significantly greater than that of CEA which was only 62%. In patients who developed liver metastases PRL remained elevated whereas CEA showed more than 100-fold increase. Therefore, we feel that CEA is a better marker for monitoring patients who developed liver metastases. From our results, we suggest that PRL can be used as a better overall marker for detecting recurrence(s) in patients with colorectal adenocarcinoma. PMID- 1419648 TI - Sialyl Tn as a prognostic marker in epithelial ovarian cancer. PMID- 1419649 TI - Draft guidance on children affected or infected by HIV. PMID- 1419647 TI - Immunological effects of alternative weekly interferon-alpha-2b and low dose interleukin-2 in patients with cancer. PMID- 1419650 TI - Secure units: behind the headlines. PMID- 1419651 TI - Nightingale's notes on nursing. PMID- 1419652 TI - The management of fractures of the hip. AB - Proximal femoral fractures are a common reason for admission to orthopaedic units, and one which may become even more regular as the population ages. Despite this, newcomers to the orthopaedic arena, such as nursing students, may be confused when faced by different hip fractures and the treatments which may be offered. This article seeks to clarify some of these points by outlining the anatomy of the proximal femoral region, various common fractures, the treatments available to the surgeon and aspects of nursing care associated with the pre and post operative phases of the patient's care. PMID- 1419653 TI - Teaching sociology: sharing learning. AB - The ideas in this article arose from discussions between two nurse educators brought together from different professional backgrounds to teach on a new Project 2000 course. It is a frank and honest account of a partnership involving two teachers--a nurse and a sociologist. It is also an illustration of theory-in use; of an attempt in the workplace to move away from the split between theories in sociology, nursing and education and their practical application. The authors discuss how they worked in partnership--planning, delivering and evaluating their contribution to the course's 18 month long common foundation programme. PMID- 1419654 TI - Nursing's brain drain. PMID- 1419655 TI - Cardiology: improving nurses' resuscitation skills. AB - Nurses have a crucial role to play in determining whether victims of cardiac arrest survive, but skills vary and, perhaps because of the onerous responsibility placed upon them, some nurses feel less than confident in using their abilities to the full. The author describes a resuscitation training course for staff in one hospital, designed to bolster confidence and to ensure all nurses are equally competent in giving assistance when cardiac arrest occurs. PMID- 1419656 TI - Education: perceptions of supernumerary status. AB - This, the first of three related articles, explores the attitudes of students, preceptors and lecturers to supernumerary status. While the contractual aspect of supernumerary status is understood by the three groups, there is confusion about the educational aspect. Next week, the reality of supernumerary status from the experience of students will be examined, while the final article will look at the role of students, preceptors, sisters/charge nurses and lecturers in the implementation of supernumerary status. PMID- 1419657 TI - Diffusing the fear of cancer. PMID- 1419658 TI - The Nat Health files. Whistle while you're sacked. PMID- 1419659 TI - Lateral nursing. Nursing's family feuding. PMID- 1419660 TI - Complementary therapy. Appropriate therapies for nurses to practise. PMID- 1419661 TI - Complementary therapy, therapeutic touch--research and reality. PMID- 1419662 TI - Complementary therapy. Research methods in complementary therapies. PMID- 1419663 TI - In-flight nursing: flying to the rescue. PMID- 1419665 TI - Championing the disadvantaged. Interview by Jean Gray. PMID- 1419664 TI - Europe: evolution in nursing. PMID- 1419666 TI - Care of people with diabetes in hospital. AB - Although most hospitals have protocols for the care of people with diabetes who are admitted as a result of their condition or other illness, deficiencies in the care offered are still regularly reported. This article explores reasons why the care of people with diabetes in hospital seems to be unsatisfactory, and proposes some solutions to the problems. PMID- 1419667 TI - An independent stoma care service. AB - This article describes the establishment of an independent stoma care service, and the problems the author encountered. Set up just over four years ago, it is one of the few independent stoma care services in the UK. It currently caters exclusively for patients in private hospitals in London and the South-East of England, and the author also holds a clinic in Harley Street. Over 300 patients benefit from the service. PMID- 1419669 TI - Education. The reality of supernumerary status. AB - This is the second of three related articles looking at the reality of supernumerary status for undergraduate nursing students in Northern Ireland. The first (1) explored students, preceptors and lecturers' perceptions of the term 'supernumerary'. Next week, the role of students, charge nurses and preceptors will be examined in relation to its implementation. This article portrays the reality of supernumerary status from the students' perspective, using diaries and a questionnaire. PMID- 1419670 TI - Health discrimination against gays. PMID- 1419668 TI - A milieu approach to dementia day care. AB - Applying the principles of therapeutic milieu, in which individual needs can be recognised within those of a group, can help people with dementia to realise their potential. The implementation of a system of care based on such an approach in a day unit is described, focusing on the need to acknowledge the essential worth of attenders and providing adequate support for staff. PMID- 1419671 TI - The Clay column. PMID- 1419672 TI - Hospital security: NHS ignores rape alarms. PMID- 1419673 TI - Employment: why on earth am I nursing? PMID- 1419674 TI - The Sister Susie column. Dog day surgery visits. PMID- 1419675 TI - Professional conduct: the UKCC Code deciphered. PMID- 1419676 TI - Lateral nursing. Consumption imperils nurses. PMID- 1419677 TI - School nursing: a slice of history. PMID- 1419678 TI - Health of the nation: the missing links. PMID- 1419679 TI - Europe: a return to criminalisation. PMID- 1419680 TI - Ensuring compliance in enteral feeding. AB - Enteral feeding provides a lifeline for some patients, but is not without its own hazards and risks. The complications include blocking of tubes and gastrointestinal intolerance, and may inhibit and delay the patient's recovery from illness. This article discusses the difficulties, and offers some potential solutions to them. PMID- 1419681 TI - Mental health: use and abuse of control and restraint. AB - The recent report of the inquiry into complaints at Ashworth Hospital (1) recommended that control and restraint techniques, used to contain violent conduct, should be used as a last resort, 'and should be subject to careful scrutiny to determine system failures'. This article, which points out that nurses in many areas are victims of increased levels of violence, defines control and restraint techniques, who should use them and in which situations their use may be sanctioned. The author concludes that although preservation of the patient's rights and dignity is paramount, nurses who have undergone control and restraint training are more confident practitioners when they are confronted with violent situations. In a second article next month, Tarbuck will look at issues of ethics and the human rights of patients. PMID- 1419682 TI - Paying health care assistants in the NHS. PMID- 1419683 TI - Current initiatives in open learning. AB - This article considers the needs for open learning in pre- and post-registration nurse, midwife and health visitor education. Examples of institutions using open learning are provided and the English National Board's current initiatives in relation to open learning packages are detailed. The Board's future initiatives demonstrating its commitment to the support of open learning are also described. PMID- 1419685 TI - Student overload is threatening nurses responsible for supervising placements. PMID- 1419684 TI - Education: implementation of supernumerary status. AB - This series of three articles began with a discussion of perceptions of supernumerary status and was followed by an examination of the reality of the term as seen through the eyes of students, teaching and ward staff. The series concludes this week with an exploration of the context in which supernumerary status can best be implemented. PMID- 1419686 TI - A day in the life. Could my big end have gone? PMID- 1419687 TI - Lateral nursing: the academic paper chase. PMID- 1419688 TI - Equal opportunities: chipping away at change. PMID- 1419689 TI - Living will allows choice for people with HIV/AIDS. PMID- 1419690 TI - AIDS focus. Educating for health. PMID- 1419692 TI - AIDS focus. HIV roundup. PMID- 1419691 TI - AIDS focus. Developing a vaccine for HIV. PMID- 1419693 TI - 'No' to blanket HIV pregnancy testing. PMID- 1419694 TI - Understanding quality (continuing education credit). PMID- 1419695 TI - Asthma explained (continuing education credit). PMID- 1419696 TI - Introducing EuroQuan. PMID- 1419697 TI - EuroQuan. Nursing standards in Europe. PMID- 1419699 TI - Primary nursing: making time for patients. PMID- 1419698 TI - EuroQuan. European quality. PMID- 1419700 TI - Off the boil on the health service. PMID- 1419701 TI - Patient autonomy: willing decisions. PMID- 1419703 TI - Whistleblowing: discipline! PMID- 1419702 TI - Relief work: don't forget Somalia. Interview by Charlotte Alderman. PMID- 1419705 TI - Clinical practice and management. PMID- 1419704 TI - Living aids: wheelchair evaluation and prescription. AB - This article reviews the assessment procedure for patients who require a wheelchair. The author, a medical specialist in prosthetics and orthotics, describes the important physical and social factors which must be considered, and defines what equipment is available from the National Health Service and elsewhere. PMID- 1419706 TI - Off-the-shelf audit: is it feasible? AB - Increasing interest in audit in the health service has focused attention on the tools and methods used to achieve it. These can be extremely expensive, so a tendency to opt for off-the-shelf packages has developed. This article reviews how one such instrument, The Central Nottinghamshire Psychiatric Nursing Audit, has been used in two settings over the past three years, with particular emphasis on its cost-effectiveness. PMID- 1419707 TI - The named nurse in perspective. AB - This is the first of three articles that concentrate on the implications of the named nurse initiative for nursing practice. The way the initiative has been put into practice in Sheffield Health Authority will be described next week, followed by Steve Wright's analysis of the value of wearing name badges. To set the scene, Royal College of Nursing General Secretary Christine Hancock takes a wider look at the concept of the named nurse and relates it to systems of organising nursing that are in general use. PMID- 1419708 TI - The standard guide to writing for publication. PMID- 1419709 TI - The cynical nurse specialist. PMID- 1419710 TI - Women's network: women at work. PMID- 1419711 TI - Student voice: witness to inhuman practices. PMID- 1419712 TI - A tremendous opportunity to influence services. PMID- 1419713 TI - Occupational risk of HIV-associated TB. PMID- 1419714 TI - Radical approach to HIV vaccine. PMID- 1419715 TI - Community care: the forgotten carers. PMID- 1419716 TI - Bosnia: victims of the violence. PMID- 1419717 TI - The new language of caring. PMID- 1419718 TI - Patrolling occupational health. Interview by Charlotte Alderman. PMID- 1419719 TI - A new development in radiology: TIPS. AB - Interventional radiology has had a significant impact on patient care over the past 20 years, with the development of low-risk procedures. Nurses specialising in this field must maintain their knowledge of innovations to ensure that the nursing care of such patients remains appropriate. This article describes the indications for and procedural technique of transjugular intrahepatic portosystemic shunting (TIPS), a new initiative in interventional radiology. Although there are risks and side-effects, initial evidence of the method's efficacy suggests it has great potential in reducing morbidity and length of hospital stay. PMID- 1419720 TI - The role of the support worker. AB - The major contribution which nurses make to patient care could be enhanced still further if nurses' professional skills were used to the full. Advances in medical technology, faster patient throughput, increasing numbers of very elderly people and higher consumer expectations have changed and extended the demands on nurses and nursing. PMID- 1419721 TI - Giving and taking constructive criticism. PMID- 1419722 TI - Patient's charter: the implementation of named nursing. PMID- 1419724 TI - Management: everybody's enemy. PMID- 1419723 TI - No nursery rhyme or reason: working parents. PMID- 1419725 TI - A day in the life. Never mind the width. PMID- 1419726 TI - The Nat Health files. The latest pet therapy. PMID- 1419727 TI - Getting the nursed degree. PMID- 1419728 TI - District nursing: another lonely death. PMID- 1419730 TI - [Children live dangerously--accident prevention a responsibility of the pediatric nurse?]. PMID- 1419731 TI - [Pension reform in force--evaluation of the new pension legislation]. PMID- 1419729 TI - [Our children's hospital aught to be more thoughtful of children]. PMID- 1419732 TI - [Informative visits to England]. PMID- 1419733 TI - [Acute appendicitis--guidelines for preoperative and postoperative care]. PMID- 1419734 TI - [Special nursing tasks in pediatric psychosomatics]. PMID- 1419735 TI - [Rudolf Degkwitz (1889-1973)]. PMID- 1419736 TI - [Meaningful environment-friendly disinfection and hygienic measures in pediatrics]. PMID- 1419737 TI - [20 years of the new building of the pediatric hospital in Gorlitz]. PMID- 1419739 TI - [Mucoviscidosis]. PMID- 1419738 TI - [Is Pediatric Nursing disappearing?]. PMID- 1419740 TI - [Pre- and postoperative care of male newborns and infants with urethral obstructions]. PMID- 1419741 TI - [The technique of endotracheal suction]. PMID- 1419742 TI - [Nurse counselor in neonatology]. PMID- 1419743 TI - [Meaningful environment-friendly disinfection and hygienic measures in pediatrics. 3]. PMID- 1419744 TI - [Poisonous and less poisonous plants. 4]. PMID- 1419746 TI - [Caries prevention. Position of the nutrition commission of the Austrian Society for Pediatric and Adolescent Medicine]. PMID- 1419745 TI - [Lues Connata--clinical aspects, diagnosis and therapy]. PMID- 1419747 TI - [Satisfaction and dissatisfaction--triggering factors in nursing performance]. PMID- 1419748 TI - [Tubingen sibling day care--day care for healthy children]. PMID- 1419749 TI - Distribution of interleukin 1 receptor antagonist protein (IRAP), interleukin 1 receptor, and interleukin 1 alpha in normal and psoriatic skin. Decreased expression of IRAP in psoriatic lesional epidermis. AB - The distribution of interleukin 1 alpha (IL-1 alpha), type 1 interleukin 1 receptor (IL-1R), and the interleukin 1 receptor antagonist protein (IRAP), was investigated in biopsies of normal skin, and in uninvolved and lesional skin of patients with psoriasis, using specific monoclonal antibodies. We report the novel finding that IRAP is distributed throughout the living layers of the epidermis in normal skin, and is also associated with sebaceous glands and eccrine sweat glands. Our finding that the inhibitor protein IRAP is present in areas where the pro-inflammatory cytokine IL-1 alpha is distributed provides strong evidence in favour of a cytokine regulatory system in normal skin. We further document for the first time that IL-1R in normal skin is localized to the living layers of the epidermis, sebaceous and eccrine glands, as well as to a prominent network of dermal dendritic cells, and upper dermal blood vessels. There was a consistent reduction in the level of IRAP expression in lesional compared with uninvolved skin in biopsies from six out of seven psoriasis patients. Decreased IRAP expression in lesions of psoriasis indicates that alterations in the level of this inhibitor protein may be important in the pathogenesis of inflammatory skin conditions. PMID- 1419751 TI - Epidermolysis bullosa in Northern Ireland. AB - Cases of epidermolysis bullosa (EB) diagnosed in Northern Ireland during a 23 year period (1962-84) were identified from dermatology clinic files, paediatric hospital notes and cases known by general practitioners. A total of 48 confirmed new cases of EB were diagnosed during the screening period. This involved 31 families, with identification of 36 further cases. The distribution of incident EB subtypes was: simplex 31 (65%), junctional 1 (2%), dystrophic 12 (25%) and acquisita 4 (8%). The incidence rate of new cases of EB diagnosed per year is 1.4/million and prevalence of all forms estimated at 32/million. The prevalence of simplex, junctional and dystrophic forms is 28, 0.7 and 3/million, respectively. PMID- 1419750 TI - Intracellular expression of type VII collagen during wound healing in severe recessive dystrophic epidermolysis bullosa and normal human skin. AB - The ability of keratinocytes to synthesize basement membrane components in vivo during wound healing in normal human skin and in severe recessive dystrophic epidermolysis bullosa (RDEB) was investigated. Indirect immunofluorescence using anti-type VII collagen (VIIc, recognizing the globular non-helical component of the molecule), anti-type IV collagen, anti-laminin and bullous pemphigoid antisera, was performed on biopsies of intact skin and of healing skin taken between 7 and 14 days after dermatome injury (upper to mid-dermal wounding) in eight patients with severe RDEB and in seven normal subjects. Baseline anti-type VIIc immunofluorescence showed completely absent staining of the epidermis, dermis and dermo-epidermal junction in severe RDEB samples, and bright linear dermo-epidermal junction fluorescence in normal human skin. In 5/5 normal human skin samples taken 9-12 days post-wounding, some type VIIc expression was noted within basal cells as well as in a continuous or interrupted linear distribution at the basement membrane zone. In all the severe RDEB biopsies sampled between days 10 and 13 (5/5), anti-VIIc fluorescence was also seen with varying intensity within basal and lowermost suprabasal cells, and in one day 14 sample at the dermo-epidermal junction. Low levels of intracellular type IVc were seen in both groups, but only in those samples taken 7-9 days after injury; later biopsies showed only continuous dermo-epidermal junction staining. Linear basement membrane zone labelling with laminin and bullous pemphigoid antisera was seen in all samples in both sets of subjects, even at day 7, but there was no detectable intracellular antisera staining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419752 TI - Exposure to house dust mites in homes of people with atopic dermatitis. AB - The median relative density of house dust mite populations was determined in mattresses in the homes of 23 people with atopic dermatitis (AD) who were mite sensitive. It was significantly higher (total mites [dead and live] 174/0.1 g of dust: live mites 45.5/0.1 g) than in those of 23 healthy non-atopics (total mites 52/0.1 g; live mites 7.5/0.1 g; P < 0.05, < 0.01, respectively; Mann-Whitney U test). There was no significant difference between mite population densities in mattresses in damp homes (n = 27; total mites 188/0.1 g; live mites 36/0.1 g) and those in homes with no damp (n = 19; total mites 116/0.1 g; live mites 26/0.1 g). These data demonstrate a clear association between AD and exposure to large numbers of mites, independent of the presence of domestic damp. People with AD were exposed to densities of > 500 mites/0.1 g of mattress dust five times more frequently than non-atopics, corresponding to a relative risk of 25.0, but were exposed to densities of < or = 50 mites/0.1 g five times less frequently. The overall relative risk for AD, with a cutoff of 50 mites (total)/0.1 g, was 8.1. There was an obvious positive correlation between magnitude of exposure and frequency of disease. It is hypothesized that the association between high densities of mites and AD is related to differences in lipid composition of the shed squames on which the mites feed: those of people with AD may be of greater nutritional value than those of non-atopics, thus enhancing mite population growth. PMID- 1419753 TI - Adhesion molecules and related proteins in Darier's disease and Hailey-Hailey disease. AB - We have used antibodies to plakoglobin and E-cadherin: the lectins, peanut agglutinin (PNA) and soybean agglutinin (SBA); and sera from patients with the autoimmune diseases pemphigus vulgaris (PV) or pemphigus foliaceus (PF), in an immunohistological study of Darier's disease and Hailey-Hailey disease. There was normal expression of plakoglobin, E-cadherin, lectins and pemphigus antigens at the periphery of keratinocytes in uninvolved skin. Clumps of plakoglobin were detected within acantholytic cells in Hailey-Hailey disease, whereas expression was diffuse in acantholytic cells in Darier's disease. This difference may reflect differences in the pathogenesis of acantholysis. E-cadherin expression was weak or absent at the periphery of some acantholytic cells; lectin binding was sometimes reduced around acantholytic cells, and pemphigus antibodies did not bind to the acantholytic cells involved skin in either disease. Internalization, conformational changes or proteolysis may alter the expression of extracellular epitopes by acantholytic cells. PMID- 1419754 TI - Increased sensory neuropeptides in nodular prurigo: a quantitative immunohistochemical analysis. AB - Seven patients with nodular prurigo, five patients with lichenified eczema and seven control volunteers were studied immunohistochemically using antisera to the pan-neuronal marker protein gene product 9.5 (PGP), and the neuropeptides calcitonin gene-related peptide (CGRP), substance P (SP), tyrosine hydroxylase (TH), vasoactive intestinal polypeptide (VIP) and the C-flanking region of neuropeptide Y (C-PON). PGP-, CGRP- and SP-immunoreactivities were also evaluated using image analysis quantification, and the data compared by statistical analysis. No significant changes were noted in the lichenified skin of patients with chronic eczema, compared with the control groups. In contrast, a significant increase in PGP immunoreactive nerve fibers was seen in lesional skin of all nodular prurigo cases studied, when compared with non-lesional skin from the same patient or from control subjects (P < 0.001). In one case massive neural hyperplasia was also identified. Staining for CGRP and SP showed a large increase of immunoreactive nerves in lesional skin of nodular prurigo patients, which closely paralleled that of PGP. Staining with VIP, C-PON and TH was similar in both lesional and non-lesional skin. These results indicate that neural changes in nodular prurigo are associated with an increase of sensory neuropeptides, which could be related to the intense pruritus which accompanies nodular prurigo. The absence of significant changes in lichenified skin suggests that the increase in CGRP- and SP-immunoreactive nerve fibres is a characteristic feature of nodular prurigo and may be important in its pathogenesis. PMID- 1419755 TI - A quantitative immunohistochemical study of the expression of integrins by nerves in psoriatic and normal skin. AB - Qualitative and quantitative assessment of integrin expression by dermal nerves was made by an avidin-biotin immunoperoxidase method on snap-frozen biopsies from affected psoriatic skin, and skin from normal control subjects with no history of skin disease. Nerves expressed alpha 1, alpha 2, alpha 3, alpha 6, beta 1 and beta 4 integrin subunits, and perineural sheaths in the mid-dermis also expressed these subunits, with the exception of alpha 2. There were more upper dermal nerve segments expressing alpha 1 integrin compared with other integrins both in controls and in psoriatic skin. The greater number of nerves expressing alpha 1 integrin compared with other integrins may be due to anatomical or functional differences between groups of nerves. There were significantly more nerves expressing alpha 1, alpha 2, alpha 3, alpha 6 and beta 4 integrins in psoriatic skin compared with control skin. This generalized increase may indicate a secondary trophic effect on all nerves rather than a specific increase in one type of nerve. However, the expression of alpha 2 integrin may be significant in the pathogenesis of the psoriatic plaque, in that it was barely detectable in the normal site-matched biopsies, but much greater in psoriatic plaques. The study of the expression of adhesion molecules by neurones in psoriasis offers a new avenue for investigation of the role of neuronal hypertrophy in the initiation and maintenance of psoriatic plaques. PMID- 1419756 TI - Peripheral anchorage of dermal equivalents. AB - Human fibroblasts can induce collagen gel contraction with different kinetics depending on the number of cells and on the collagen concentration within this lattice, which has been considered as a dermal equivalent. Skin equivalent is a combined culture of dermo-epidermal layers which may be of therapeutic value in the treatment of burn patients. However, the current production of the dermal equivalent component gives results that present many drawbacks for their eventual clinical use as a first step in obtaining a skin equivalent. These include: (i) final surfaces which are very small; less than 20% of the initial size (ii) excessive thickness which may hamper successful graft take (iii) fibroblasts that do not have an arrangement comparable with normal dermal tissue. We propose, as a solution to these problems, the utilization of a 5-mm-wide fibre-glass filter ring peripherally attached to the surface of the Petri dishes to prevent inordinate contraction while the fibroblasts reorganize the collagen gel. Using this technique the initial surface was preserved and the dermal equivalent contracted only in thickness. Histological analysis of these anchored equivalents confirmed an alignment of fibroblasts and collagen fibres resembling normal dermal tissue. We consider this method useful in the development of dermo epidermal sheets for clinical purposes. PMID- 1419758 TI - Sensitivity of different areas of the flexor aspect of the human forearm to corticosteroid-induced skin blanching. AB - The intensity of corticosteroid-induced blanching has been found to vary at different areas of the flexor aspect of the human forearm. A retrospective analysis of 38,880 observations of skin blanching in 56 volunteers was conducted to assess the sensitivity of forearm skin to betamethasone 17-valerate. The mid forearm appears to be more sensitive to the blanching response than do the areas close to the wrist or elbow. These results indicate that each preparation under evaluation should be applied to several sites along the forearm when using the human skin blanching assay in order to obtain an accurate comparative assessment of corticosteroid release from topical delivery vehicles. PMID- 1419759 TI - Bone changes and their significance in children with ichthyosis on long-term etretinate therapy. AB - Anxiety about the use of etretinate in children has been provoked by several reports describing skeletal abnormalities during long-term therapy. However, we have observed no evidence of skeletal toxicity in 42 children treated over an 11 year period. Radiological screening before and during treatment has failed to reveal abnormalities that would influence our decision to commence or to continue etretinate administration. We recommend that children who are to be treated with etretinate should have a baseline selective skeletal survey, with follow-up radiology restricted to those with pretreatment radiological abnormalities and those who develop musculo-skeletal symptoms. In addition we advise that dosage should not exceed 1 mg/kg/day. If these guidelines are followed, we believe that long-term therapy with etretinate can be given to children, with an acceptable margin of safety. PMID- 1419757 TI - Isolation and characterization of a lower molecular weight protein doublet of horny cell outer leaflet: a possible novel epidermal differentiation marker. AB - The water-soluble fraction of stratum corneum contains numerous unidentifiable proteins and polypeptides when examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Intensely stained polypeptide bands of low molecular weights (LMW) [8 and 10 kDa] are also present, and the abundance and invariable presence of this LMW protein doublet in the soluble proteins of stratum corneum prompted us to isolate and characterize them. Extracts of stratum corneum, using 8 M urea, 0.05 M Tris, pH 9.0, 0.025 M 2-mercaptoethanol, were dialysed against water. Water-insoluble proteins were removed by repeated dialysis and centrifugation. From the remaining soluble proteins, a LMW protein doublet was isolated by Sephadex G50 column chromatography and reversed-phase high-performance liquid chromatography (HPLC). The amino acid compositions of the 8 and 10 kDa proteins were similar to, but different from, those of known structural proteins in the stratum corneum. Rabbit antibody was raised against the 10-kDa protein band and cross-reacted with the 8-kDa protein band by Western immunoblot technique. The antibody recognized only this protein doublet amongst the proteins extracted from cultured keratinocytes. The 8- and 10-kDa proteins therefore appear to be closely related to, but different from, known structural proteins or degradation products. Immunofluorescence and immunoelectron microscopy demonstrated that this protein doublet was located in the cytoplasm of the cells of the malpighian layer, and in the outer layer of the marginal band of the horny layer. Its distribution was shown to be limited to stratified squamous epithelia by organ specificity studies. These results suggest that this protein doublet appears to be a novel soluble protein and a new epidermal differentiation marker of stratified epithelium. PMID- 1419760 TI - Bath-water compared with oral delivery of 8-methoxypsoralen PUVA therapy for chronic plaque psoriasis. AB - Forty-four patients with chronic plaque psoriasis were randomly allocated to treatment with bath-water-delivered 8-methoxypsoralen (bath 8-MOP) or oral 8 methoxypsoralen (oral 8-MOP) PUVA therapy. There was a significant reduction in extent of the lesions and psoriasis area and severity index (PASI) after 20 treatments with each modality. There was a fourfold reduction in cumulative ultraviolet A (UVA) dose in the bath group. Side-effects of erythema and nausea were less with bath therapy. PMID- 1419761 TI - An investigation of the pharmacokinetics of topical terbinafine (Lamisil) 1% cream. AB - Twenty human volunteers were entered into a study to investigate the pharmacokinetics of terbinafine 1% cream. Subjects were randomized to receive terbinafine 1% cream applied to the back on 1 day, or on 3, 5 or 7 consecutive days. Up to five sequential skin surface biopsies were taken at a site on the upper back at various time-points both during treatment, and following cessation of treatment. Terbinafine levels in these biopsies were analysed using HPLC. The study showed that increasing the number of applications from one to seven did not significantly increase the peak concentration (Cmax) in the stratum corneum. It did, however, increase the total amount of terbinafine found in the stratum corneum, resulting in terbinafine being detected for longer periods after cessation of therapy. Treatment for 7 days resulted in terbinafine still being detectable 7 days after cessation of therapy, when the terbinafine concentration was significantly higher than the known cidal concentrations for the common causative organisms of superficial dermatomycoses. This study indicates a significant potential for short-duration treatment with terbinafine (Lamisil) 1% cream in superficial dermatomycoses. PMID- 1419762 TI - Phenytoin-induced pseudolymphoma. A report of a case and review of the literature. AB - We report a patient with phenytoin-induced pseudolymphoma mimicking cutaneous T cell lymphoma (CTCL). Despite withdrawal of phenytoin, there was persistence of the cutaneous eruption and lymphadenopathy. Southern blot analysis of immunoglobulin and T-cell receptor genes was therefore used to assess whether there was a clonal lymphoid expansion. However, no rearrangement of the beta T cell receptor gene or immunoglobulin heavy-chain gene was detected in tissue DNA from skin and lymph nodes. One year later the patient became asymptomatic, although he is still at risk of developing a true malignant lymphoma in the future, a condition known as pseudo-pseudolymphoma. It is suggested that genotypic studies may help in the initial diagnosis and the subsequent management of such patients. PMID- 1419763 TI - Centrifugal lipodystrophy of the face mimicking progressive lipodystrophy. AB - We report a Japanese boy with centrifugal lipodystrophy. The initial lesion developed on the forehead as an area of erythema which showed centrifugal spread and central fading to leave a residual depression. Three years later, similar erythematous lesions appeared on the cheeks, and he developed a cadaverous appearance. A central depression on the upper trunk was surrounded by an erythematous border and there was right cervical lymphadenopathy. Histological examination revealed inflammatory changes in the subcutaneous fat. Although this patient showed the characteristics of both centrifugal and progressive lipodystrophy (partial lipodystrophy), we consider that he has centrifugal lipodystrophy of the face because of the overall features of the lesions. PMID- 1419764 TI - Elephantiasis nostras verrucosa: beneficial effect of oral etretinate therapy. AB - Elephantiasis nostras verrucosa is characterized by chronic secondary, non filarial lymphoedema due to recurrent lymphangitis, dermal fibrosis, and epidermal changes consisting of hyperkeratotic, verrucous and papillomatous lesions. Histologically, there is pseudoepitheliomatous hyperplasia. Therapeutic efforts should aim to reduce lymph stasis, which will also lead to improvement of the cutaneous changes. In this study, rapid disappearance of the hyperkeratotic and verrucous lesions, remarkable flattening of the papillomatous nodules and improvement of lymphoedema occurred in three obese patients treated with etretinate in an initial dose of 0.6-0.75 mg/kg/day for 4-6 weeks. Monitoring of plasma concentrations of etretinate, acitretin and 13-cis-acitretin by HPLC revealed sufficient short-time absorption (4 h) and bioavailability of the drug (30 days; two out of three patients). Long-term maintenance therapy in one patient produced a remarkable improvement in the lymphoedema; another patient relapsed after discontinuation of the etretinate and responded again after this was reintroduced. In the third patient treatment was withdrawn because of an increase in triglycerides, but improvement persisted 6 months later. The clinical side-effects of oral retinoid therapy were moderate and well tolerated. PMID- 1419765 TI - British Society for Investigative Dermatology. Annual meeting. Sheffield, 24-25 September 1992. Abstracts. PMID- 1419766 TI - A case of malignant haemangioendothelioma showing response to interleukin 2 therapy. PMID- 1419767 TI - Subacute cutaneous lupus erythematosus-like gyrate erythema and hypertrichosis lanuginosa acquisita associated with uterine adenocarcinoma. PMID- 1419768 TI - Unusual pattern of phototoxic burning following trimethylpsoralen (TMP) bath photochemotherapy (PUVA) PMID- 1419769 TI - Lesional blistering following narrow-band (TL-01) UVB phototherapy for psoriasis: a report of four cases. PMID- 1419770 TI - Discoid lupus erythematosus-like lesions in carriers of X-linked chronic granulomatous disease. PMID- 1419771 TI - Median nail dystrophy associated with isotretinoin therapy. PMID- 1419772 TI - Extracorporeal photochemotherapy in the treatment of severe psoriatic arthropathy. PMID- 1419773 TI - Malignant melanoma occurring as a second cancer following primary germ cell tumour in males: report of three cases. PMID- 1419774 TI - Comparative teratogenicity of nine retinoids in the rat. AB - he comparative teratogenicity of nine retinoids in Wistar rats was investigated. The compounds studied and dose levels tested (mg/kg) were: all-trans-retinoic acid (TRA), 6.25, 12.5, 25, 50, 100; etretinate (ETR), 25, 50; acitretin (ACIT), 25, 50; 13-cis-retinoic acid (13CRA), 100, 200; and five retinamides, each at 300 and 600 mg/kg, N-(4-hydroxyphenyl)-retinamide (4HPR); N-tetrazol-5-ylretinamide (TZR); N-butylretinamide (NBR); N-ethylretinamide (NER); 13-cis-N-ethylretinamide (13CNER). Retinoids were administered by oral intubation on days 10 and 11 post coitum (p.c.). Dams were killed on day 22 p.c. and examinations carried out to assess teratogenic potential. TRA, ETR, ACIT, 13CRA and 4HPR increased the incidence of resorptions. The incidence of abnormal fetuses, irrespective of the specific abnormalities induced, was markedly increased (50-100%) by TRA, ETR, ACIT, 13CRA and 4HPR, whereas TZR and NBR caused moderate increases (20-50%), and NER and 13CNER induced mild increases (10-20%). The incidences of CNS, craniofacial and urinogenital defects were generally high with TRA, ETR, ACIT and 13CRA. Cardiac vessel defects were markedly increased by 4HPR. Using a number of criteria, a generalized ranking order of the toxicity of the compounds was drawn up: TRA > ETR > ACIT > 13CRA > 4HPR > TZR identical to NBR > NER identical to 13CNER. The ranked order of relative in-vivo teratogenicity for the nine retinoids is compared with a previously reported in-vitro assessment of the compounds using a rat whole embryo culture technique. PMID- 1419776 TI - Binding of asparaginase to mouse monocytes. AB - We have demonstrated that biotinylated asparaginase binds to mouse monocytes. Also, asparaginase bound to peritoneal exudate, resident, splenic, bone marrow and pulmonary macrophages, but not to neutrophils or lymphocytes. Labelled asparaginase binding to peritoneal exudate macrophages was inhibited by 20-fold excess of unlabelled asparaginase. The binding of asparaginase to monocytes from mice injected with lactic dehydrogenase virus (LDV) or carrageenan was decreased. This decreased binding following treatment with LDV or carrageenan was reversed when mice were treated with diethylstilboestrol. In-vivo asparaginase clearance in mice infected with LDV was impaired as compared with that in uninfected mice. Neither strain nor age differences affected the binding to monocytes. The results suggest that the ability of asparaginase to bind to monocytes in vitro may reflect clearance function in vivo. PMID- 1419775 TI - Measurements of blood flow and histometry of the cellular infiltrate in tuberculin skin test responses of the typical Koch type and the non-turgid variant form (Listeria-type) in pulmonary tuberculosis patients and apparently healthy controls. AB - The typical turgid Koch type and the non-turgid variant form (Listeria-type) of the tuberculin skin test responses were studied in 76 newly diagnosed pulmonary tuberculosis patients and 29 apparently healthy factory worker controls from Surabaya in Indonesia; in general, the patients had more intense responses than the controls. The blood flow velocity (RBCflux) at the centre of the reaction was similar in all groups, but central relative slowing (a presumed forme fruste of severe ischaemia) was much more common in the Koch-type reactions in tuberculosis patients. In both groups of subjects, the overall density of cellular infiltrate (and the major populations of inflammatory cells) was greater in the typical Koch type reactions than in the non-turgid variant reactions. Thus the Koch-type reactions were indubitably more intense in inflammatory terms than the non-turgid variant form, but the results of this study do not exclude the possibility that there were underlying qualitative differences in pathogenesis between reactions of the two types as well as the obvious difference in severity. PMID- 1419777 TI - Lactic dehydrogenase virus infection prevents development of anti-nuclear antibody in (NZB x NZW)F1 mice; role of prostaglandin E2 and macrophage Ia antigen expression. AB - Persistent lactic dehydrogenase virus (LDV) infection prevents the development of antinuclear antibody (ANA) in (NZB x NZW)F1 mice. To assess the suppressive mechanisms, we focused on the role of the E series of prostaglandin(PGE), since previously we have shown enhanced production of PGE by macrophages from chronically LDV-infected mice. Treatment with PGE2 suppressed ANA titres more markedly in non-infected mice than in LDV-infected mice. Indomethacin enhanced ANA titres more markedly in LDV-infected mice than in non-infected mice. The number of Ia antigen positive(Ia+) macrophages was less in LDV-infected mice than in uninfected mice. The number of Ia+ macrophages was decreased in non-infected mice by PGE2 treatment and increased in LDV-infected mice by indomethacin treatment. These results suggest that the low ANA production in LDV-infected (NZB x NZW)F1 mice may be related to the decreased number of Ia+ macrophages and that one of the factors responsible for suppression of Ia+ macrophages may be the enhanced PGE2 production in the LDV-infected mice. PMID- 1419779 TI - Detection of leptospiral antigen (L. interrogans serovar copenhageni serogroup Icterohaemorrhagiae) by immunoelectron microscopy in the liver and kidney of experimentally infected guinea-pigs. AB - Guinea-pigs were experimentally infected with L. interrogans serovar copenhageni serogroup Icterohaemorrhagiae and their liver and kidney were studied by immunoelectron microscopy using the post embedding indirect immunogold labelling technique. Primary antibody was a purified rabbit anti-serum produced against the same leptospiral strain used in the inoculum. Gold-labelled leptospiral antigen (LAg) was found close to cell membranes of hepatocytes, kidney tubular cells and endothelial cells of the interstitial capillaries of the kidney. Afterwards it was internalized by hepatic and tubular cells, and eventually found in lysosomes. Phagolysosomes of Kupffer cells were also found to contain remnants of degraded leptospires and gold-labelled LAg. Gold-labelled intact leptospires were detected at the enlarged intercellular spaces between hepatocytes at the areas of hepatic cell plate disarray, showing the potential for leptospiral migration during the septicaemic phase of the disease potentially contributing to the pathogenesis of the lesions. The affinity of leptospiral antigenic material for cell membranes suggests an initial interaction with cell surface proteins followed by its internalization and cell damage. The nature of antigenic material detected, however, remains undefined; it may be a toxin, an enzyme or any other factor/s involved in leptospiral virulence. PMID- 1419778 TI - The development of an in-vitro perfusion system for studies on cultured cells. AB - The design and use of a perfusion system, using a modified flow chamber for studies on cultured animal cells, is described. Rat thoracic aorta smooth muscle cells were isolated by an explant method and grown on Thermanox coverslips. These were introduced into the flow chamber. A flow rate of 25ml/min and a shear stress of 14.6 dynes/cm2 (12 dyne = 10 microN) (both within physiological limits) were maintained. Cells remained attached to the coverslips after 8h of perfusion with culture medium. The effect of exposing rat smooth muscle cells to the cardiovascular toxin, allylamine, is also described. The components of the system are routinely available, simple to clean, easy to assemble and sterilize. The incorporation of an in-line sensor that monitors pH, PO2, PCO2 and temperature ensures that the perfusion conditions remain within physiological limits. Automation means that minimal supervision is required. This system provides a potential mechanism in which cultured vascular cells may be perfused under controlled haemodynamic conditions, and their response to a cytotoxin may be evaluated. PMID- 1419780 TI - Protoporphyrin overload in unrestrained rats: biochemical and histopathologic characterization of a new model of protoporphyric hepatopathy. AB - We determined the feasibility of producing protoporphyric hepatopathy in unrestrained rats by infusing protoporphyrin into their portal circulation via chronic indwelling catheters. Sprague-Dawley rats, 200-300 g, received single (8.5-27.8 mumol) or multiple (64.1-208.7 mumol) infusions of protoporphyrin over 3-240 h. Single protoporphyrin infusions increased the hepatic protoporphyrin concentration from < 1 nmol/g up to 1368 nmol/g; multiple infusions up to 3908 nmol/g. The maximal non-hepatic tissue concentrations averaged 243 nmol/g in the spleen. Hepatocanalicular and ductular birefringent pigmented deposits were found in all livers, generally proportional to the protoporphyrin load. Aggregates of crystalline protoporphyrin were detected in biliary ductules, canaliculi, hepatocytes, Kupffer cells and fat-storage cells by electron microscopy. Laboratory abnormalities included elevations of the transaminases, LDH, GGTP and bilirubin and a modest fall in the haematocrit suggesting a mixture of red blood cell and hepatic injury. Thus, protoporphyric hepatopathy was produced by infusions of protoporphyrin into the portal circulation. This model may aid in understanding the pathogenesis and pathophysiology of liver disease in protoporphyria. PMID- 1419781 TI - The immunocytochemical localization of tumour necrosis factor and leukotriene in the rat liver after treatment with lipopolysaccharide. AB - After administration of bacterial lipopolysaccharide, there is an increase in the number of leucocytes which adhere to the endothelial cell surface of the hepatic vessels and pass through the endothelial layer by comparison with controls. There is also marked endothelial cell damage including intracytoplasmic oedema, increased numbers of autophagic vacuoles and dilatation of the intercellular junction in LPS-treated samples. The presence of immunocytochemical products of leukotriene (LTR) and tumour necrosis factor (TNF) was examined using in both LPS treated and control samples. Immunoreactions of LTR which were seen in specific granules of neutrophils and monocytes attached to the endothelial cell surface may indicate the onset of endothelial cell damage. Positive immunoreactions of TNF on the endothelial cell surface, seen only in LPS-treated samples, indicate that TNF may enhance the passage of blood cells through the endothelia and also increase the endocytotic activity of the liver parenchymal cells, as revealed by the present marker experiment using horseradish peroxidase. Positive reactions of TNF in lysosomes of the endothelial cells suggest that they are able to produce TNF and transport it to the cell surface. PMID- 1419782 TI - The pathology of rat lung isografts following 48 or 72-hour cold storage and subsequent reperfusion in vivo for up to 1 month. AB - Using a left lung orthotopic isograft model in adult male AS strain rats, the pathology of lungs which were stored for 48 or 72 hours using a simple organ flush technique followed by low temperature (0 degrees C) immersion has been investigated. Lungs were examined after cold storage alone and after storage followed by either brief (up to 1 hour) or extended (30 days) reperfusion with blood in vivo. Grafts were flushed with either isotonic saline (NaCl) or hypertonic citrate solution (HCA) alone, or with HCA containing either verapamil (a Ca(2+)-channel blocker) or prostacyclin (PGI2 which has both anti-platelet and vasodilator actions). Controls included fresh non-flushed lungs and fresh HCA flushed lungs which were transplanted immediately after harvest. After prolonged (48 or 72-hour) cold ischaemia alone the only clear change in lung morphology was of nuclear swelling. Early reperfusion changes included: (i) oedema (interstitial and alveolar); (ii) vascular congestion; and (iii) intra-alveolar haemorrhage. Features (i) and (ii) were diffuse whilst haemorrhage was patchy. Lungs which remained in vivo for up to 30 days showed focal scarring and chronic inflammation with numerous macrophages containing haemosiderin; the extent of the changes observed in individual grafts tended to mirror the gross macroscopic outcome. Attempts to improve the cold ischaemic tolerance with added agents (verapamil and prostacyclin PGI2) failed to produce a clear advantage. PMID- 1419783 TI - Australian beta zero-thalassaemia: a high haemoglobin A2 beta zero-thalassaemia due to a 12 kb deletion commencing 5' to the beta-globin gene. AB - A large novel deletional beta zero-thalassaemia mutation associated with unusually high levels of haemoglobin A2 in heterozygotes is described in an Australian family. The deletion was characterized by restriction enzyme analysis followed by PCR amplification and sequencing of the breakpoint region. Australian beta zero-thalassaemia extends from 835 basepairs (bp) 5' to the cap site of the beta-globin gene downstream for 12.023 kb. This deletion, similar to previously described deletional beta zero-thalassaemias associated with high Hb A2, removes sequences 5' to the beta-globin gene promoter and emphasizes the functional importance of the 5' beta-globin region in eliciting the unusually high Hb A2 phenotype. PMID- 1419784 TI - Improved post-transfusion quality of density separated AS-3 red cells after extended storage. AB - A centrifugal method of red cell density separation was utilized for unit processing in these studies to determine the quality of the lighter fraction (neocytes) after storage for up to 42 d and to evaluate whether the heavier fraction (gerocytes) deteriorated more rapidly than neocytes during storage. Each unit was passed through a Leukotrap filter to remove white cells prior to density separation. Red cell recovery and survival were evaluated using double label technetium-99m with either chromium-51 or nonradioisotopic chromium which permitted concurrent paired analysis. In vivo neocyte red cell recovery, as tested on the same 11 donors on days 1, 7 and 42 of storage, was effectively unchanged. Recovery and survival half-life (that is, the number of days after transfusion at which half of the cells infused remain in the circulation) of 42 d stored gerocytes were significantly lower than similarly stored neocytes (75.5 +/ 7.2% and 20.1 +/- 6.5 d for gerocytes versus 84.4 +/- 4.9% and 39.0 +/- 9.0 d for neocytes). One-day stored neocytes showed a 16.5% increase in red cell availability over the combined average for 42 d stored neocytes and gerocytes. Statistically, while there were significantly higher ATP, 2,3-DPG, and lactate levels pre-storage by paired t-test for neocytes compared to gerocytes, by day 42 there were no significant differences detected between the two red cell fractions by any of the in vitro variables measured. These studies suggest that this simple separation technique for leucocyte-poor red cell units provides a neocyte population with improved viability and the potential for increased transfusion intervals in chronically transfused patients. PMID- 1419785 TI - Band 3-Memphis is associated with a lower transport rate of phosphoenolpyruvate. AB - Band 3-Memphis is the most common variant of erythrocyte band 3 protein, in which a single amino acid substitution (Lys56-->Glu) in a cytoplasmic domain of band 3 has been found. We showed here that the prevalence of the variant was particularly higher in the Japanese population than that in other populations. The calculated gene frequency of the variant in Japanese was 0.156, which was about 4 times higher than that in Caucasian. Although it has been generally accepted that the cytoplasmic domain of band 3 bears no relation to anion transport activity, we found that the transport rate of phosphoenolpyruvate in erythrocytes of homozygotes was decreased to about 80% of that in control cells, and that of heterozygotes was at an intermediate level. The evidence indicates that some structural changes in the cytoplasmic domain of band 3 may have influence on the conformation of anion transport system. PMID- 1419786 TI - Identification of autoantigens in autoimmune haemolytic anaemia by a non radioisotope immunoprecipitation method. AB - In human autoimmune anaemia (AIHA), warm autoantibodies frequently appear to have serological specificity for the Rh complex, but to date, immunochemical techniques have failed to demonstrate that the antibodies react with Rh associated polypeptides. We describe the immunoprecipitation of red blood cell (RBC) autoantigens, using biotin labelling and a luminescent detection method. In three cases of warm AIHA, a band of 32 kD and a diffuse zone of 38-51 kD or 40-51 kD were specifically precipitated by eluted RBC autoantibody. This pattern corresponds closely with that precipitated by two Rh-specific monoclonal antibodies, BRIC 207 and AB5. Antibody from the three eluates also showed serological specificity for the Rh complex in a haemagglutination assay against a panel of RBC with a range of Rh phenotypes, including rare -D-/-D- and Rh null cells. Eluted autoantibody from another warm AIHA patient immunoprecipitated a peptide of 67 kD that did not correspond in apparent molecular mass either with Rh-associated bands, or with major RBC membrane proteins or sialoglycoproteins (SGP). The haemagglutination assay showed that this eluate contained both Rh specific and Rh-unrelated antibody. Warm autoantibody eluted from the RBC of a clinically normal, but direct antiglobulin test positive, blood donor was serologically unreactive with the Rh complex, and immunoprecipitated unknown peptides of 26, 29, 35, 48 and 51 kD, together with a band of 90 kD that comigrated with SGP alpha 2 (glycophorin A). In six further warm AIHA cases, no antigens were precipitated by autoantibody-containing RBC eluates. Overall, the results demonstrate that autoantibodies bind to Rh polypeptides in some, but not all, patients with warm AIHA, suggesting that the aetiology of the disease may vary. PMID- 1419787 TI - Effect of orally active hydroxypyridinone iron chelators on human lymphocyte function. AB - Several iron chelators, 3-hydroxypyridin-4-ones (CP) and desferrioxamine (DF) were compared for their effect on DNA synthesis, cell viability and expression of cell proliferation markers. Short-term (4 h) exposure of human peripheral blood mononuclear cells to CP or DF inhibited the proliferative response of cells to concanavalin A (Con A). Inhibition by CP and DF showed a dose-dependent effect with CP compounds more active than DF. Increased inhibitory activity of CP over DF was partly due to the lipophilic properties of CP. Pre-saturation of CP and DF with exogenous ferric ion either diminished or prevented the inhibitory effect. At high chelator concentrations or prolonged (72 h) exposure of the cells to chelators, inhibition occurred but poor cell viability was observed. In contrast to their inhibition of DNA synthesis, these iron chelators showed little effect on protein synthesis and the expression of transferrin receptors and interleukin 2 (IL-2) receptors. These findings suggest that both DF and CP compounds exert their effect by chelation of ferric ion with subsequent inhibition of DNA synthesis. PMID- 1419788 TI - Hereditary stomatocytosis: phenotypical expression of sodium transport and band 7 peptides in 44 cases. AB - The clinical heterogeneity and the role of red cell membrane protein band 7 in membrane transport were studied in 44 patients with hereditary stomatocytosis with normal red cell membrane lipids. These patients were arbitrarily categorized into three phenotypes, based on the extent of sodium influx: hereditary stomatocytosis Type I: with markedly increased Na influx (8.90 +/- 3.39 mmol/lRBC/h); Type II: with moderately increased Na influx (2.10 +/- 0.79) and Type III with normal Na influx (1.31 +/- 0.13). The three groups of patients were compared with normal controls (1.29 +/- 0.14). The extent of anaemia and jaundice was almost identical in the three groups in the presence of nearly the same degree of stomatocytosis (I: 54.8 +/- 10.7%, II: 38.8 +/- 12.8, and III: 40.2 +/- 10.8). Approximately one third of the cases (14/44) with hereditary stomatocytosis showed no overt haemolysis even with marked stomatocytosis. Cell hydration was abnormal in Type I (MCV 119.6 +/- 8.5 fl, MCHC 29.3 +/- 1.8%) but normal in Types II and III (MCV 98.2 +/- 11.7, 94.1 +/- 8.5; MCHC 34.4 +/- 2.1, 34.5 +/- 2.2). These results indicate that there was no correlation between the extent of Na influx and either the degree of stomatocytosis or the extent of overt haemolysis. The role of band 7 in membrane transport was also studied. Three components (30 kD, 28 kD and 26 kD polypeptides) of band 7 were analysed by SDS-PAGE and NEPHGE/SDS-PAGE, and the content of these polypeptides were expressed as the ratio to band 5. The 30 kDa polypeptide in the three groups was nearly identical to that in normal controls (12.3 +/- 4.0), except for non haemolysing patients in Type II. The 28 kD peptide was also decreased in five out of nine cases of Type II (25.7 +/- 5.6) as compared with normal controls (32.9 +/ 3.6) and cases of Type I (35.8 +/- 2.8) and Type III (32.7 +/- 2.9). No deficiency of this peptide was noted in Type I patients. No correlation was observed between the content of the 28 kD polypeptide and Na influx (r = 0.416), but the 26 kD polypeptide tended to be elevated in cases with overt haemolysis. These results suggest that band 7 may not be essentially involved in the formation of stomatocytic changes, although the presence of subtle defects in band 7 structure and function may not be ruled out. The present findings provide an important starting point to initiate further extensive investigations. PMID- 1419789 TI - Mitogenic role for extracellular calmodulin-like activity in normal human umbilical vein endothelial cells. AB - Normal human umbilical vein endothelial cells cultured on gelatin-coated plastic dishes were found to produce a protein in their media which had calmodulin-like immunoreactivity and biological activity. Further identification of the protein was achieved by examining the incorporation of 14C leucine into protein found in the conditioned medium. Cells produced 14C labelled protein in their medium which specifically bound to an affinity column for calmodulin. This latter material stimulated calmodulin dependent phosphodiesterase activity in vitro and this stimulation was inhibited by the addition of the calmodulin antagonist W7. The presence of calmodulin-like activity and immunoreactivity in the media varied as the cells grew from low to high density, a peak of extracellular calmodulin-like activity preceding an increase in cell number. Extracellular calmodulin-like activity did not correlate with the presence of lactate dehydrogenase in the medium. The addition of pure pig brain calmodulin affected the rate of cell proliferation; significant proliferation to pure calmodulin was only seen in cells at low density, at higher density calmodulin either had no effect or inhibited proliferation. Inhibition of extracellular calmodulin activity by a calmodulin antagonist immobilized on agarose beads, or by an antibody to calmodulin significantly decreased proliferation in all dividing cultures. Taken together this data suggests that, in vitro, calmodulin, or a very closely related protein, influences endothelial cell proliferation through an autocrine mechanism. PMID- 1419790 TI - Neutrophil-releasing activity of recombinant human granulocyte-macrophage colony stimulating factor in myelokathexis. PMID- 1419791 TI - Efficacy of high-dose intravenous gammaglobulin in the management of acquired von Willebrand's disease during orthopaedic surgery. PMID- 1419792 TI - A patient with marked leucocytosis, t(8;21), absent Philadelphia chromosome, but rearranged BCR gene. PMID- 1419793 TI - Antiplatelet antibodies in idiopathic thrombocytopenic purpura. PMID- 1419794 TI - Intensive induction chemotherapy in elderly patients. The BGMT Group. PMID- 1419795 TI - Function of acid-treated platelets for transfusion. PMID- 1419796 TI - Exercise-induced variations of lymphocytosis in the lymphoproliferative disease of large granular lymphocytes. PMID- 1419797 TI - CNS-directed therapy in childhood acute lymphoblastic leukaemia. PMID- 1419798 TI - Quantitation of granulocyte antibodies in sera and determination of their binding sites. AB - An enzyme immunoassay using eluates was developed for the quantitation of granulocyte antibodies in sera. Incubation of donor granulocytes with sera containing granulocyte alloantibodies (NA1, NA2, NB1, 5b, HLA) or autoantibodies resulted in a significantly higher amount of immunoglobulin G (IgG) per cell than did incubation with control sera. Ultracentrifugation of the sera prior to testing reduced unspecific binding of IgG to granulocytes. In eight of 10 assessed sera from patients with Felty's syndrome eluted IgG decreased from elevated to normal levels. Ultracentrifugation further allowed determination of the binding sites of granulocyte-reactive alloantibodies. Using sera containing NA1- and NA2-specific alloantibodies 173,000-188,000 binding sites on homozygous and 84,000-110,000 on heterozygous cells were determined. A similar number was found using a Fc gamma receptor III (FcRIII)-specific monoclonal antibody. Granulocytes from patients with paroxysmal nocturnal haemoglobinuria showed greatly reduced binding sites for NA-specific alloantibodies. The binding sites for the human alloantibody NB1 ranged from 36,000 to 318,000 and for the 5b alloantibody from 44,000 to 65,000. Mean values of 139,000 binding sites for HLA antigens and 27,000 binding sites for the FcRII were determined using monoclonal antibodies. PMID- 1419799 TI - Establishment of a novel granulocytic sarcoma cell line which can adhere to dermal fibroblasts from a patient with granulocytic sarcoma in dermal tissues and myelofibrosis. AB - A novel human myeloid cell line, designated HSM-1, has been established from the pleural effusion of a patient with granulocytic sarcoma (GS) who had been followed as having primary myelofibrosis for 10 years. When he was diagnosed as having granulocytic sarcoma in dermal tissues, no evidence of malignant transformation into leukaemia was found in both the peripheral blood and bone marrow. The established cell line was positive for myeloperoxidase, Sudan black B, Naphthol AS-D chloroacetate esterase. Surface marker analysis revealed that HSM-1 expressed CD4, CD13, CD11a, CD11b, Leu8, CD49b, CD49d, CD49e, CD29 and HLA DR. To clarify why the unusual myeloid tumours developed in non-haematopoietic tissues, we examined the capability of HSM-1 to bind to skin fibroblast layers. The HSM-1 cells were found to bind to both bone marrow stromal layers and skin fibroblast layers. Among the other myeloid cell lines tested, none was found to bind to skin fibroblast layers. These findings suggest that the GS cell line may be derived from a haematopoietic precursor cell which can bind to skin fibroblasts and is localized in non-haematopoietic tissues resulting in the formation of extramedullary myeloid metaplasia. HSM-1 is a useful tool for analysing the characteristics of granulocytic sarcoma and homing receptors for haematopoietic stem cells. PMID- 1419801 TI - Comparison of plasma cell infiltration in bone marrow biopsies and aspirates in patients with multiple myeloma. AB - In 54 patients with multiple myeloma plasma cell infiltration was compared in bone marrow biopsies and aspirates. In 48% of cases plasma cell infiltration was comparable, in 48% infiltration in the aspirate was lower than in the biopsy. In only two cases more plasma cells were found in the aspirate. Eleven patients (20%) had less than 20% plasma cells in the aspirate and more than 50% in the biopsy. Underestimation of plasma cell load especially seems to occur in patients with a focal growth pattern of multiple myeloma or when strong fibrosis is present. 69% of patients with stage III, according to Durie & Salmon (1975), and 76% of patients with a high beta 2-microglobulin had more than 50% plasma cells in the biopsy, indicating that these parameters, which are based on tumour load, are influenced by other factors as well. The bone marrow biopsy is of superior value for direct estimation of the tumour load in multiple myeloma compared to bone marrow aspirates. A prospective study is needed to determine its prognostic significance. PMID- 1419800 TI - Monitoring of multiple myeloma and bone marrow fibrosis with aminoterminal propeptide of type III collagen (PIIINP). AB - Bone marrow fibrosis is known in myelomatosis and depends on the extent of plasma cell infiltration. The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) has previously been reported to reflect fibrogenesis in the marrow in myelofibrosis. Here we followed 15 consecutive patients with newly diagnosed multiple myeloma with repeated PIIINP measurements during treatment with intermittent courses of melphalan and prednisolone. PIIINP was found to change with clinical behaviour of the disease, nonresponders and patients with recurrent disease having elevated values and the values in responders decreasing to the normal level or remaining there. Collagen fibres in plasma cell infiltrates of biopsies from bone marrow or skeletal tumours of these patients stained heavily with antibodies against PIIINP. Our results suggest that PIIINP works as a noninvasive indicator of bone marrow fibrogenesis. In multiple myeloma PIIINP is a sensitive, but not specific marker of disease course. PMID- 1419802 TI - Variable expression of features of normal and neoplastic stem cells in patients with thrombocytosis. AB - Essential thrombocytosis (ET) is currently diagnosed by histopathologic assessment of the marrow after exclusion of a secondary cause or another myeloproliferative disorder. To evaluate the potential of more direct diagnostic methods, we compared the frequency and association of several abnormal features characteristic of neoplastic precursors in 32 patients presenting with platelet counts > 500 x 10(9)/l. Assays for erythropoietin (Ep)-independent erythroid progenitors were performed on all patients, determination of the cycling status of circulating progenitors on 27, and assessment of granulocyte clonality on 15. In most, but not all, patients deregulated progenitor turnover. Ep-independent progenitors and clonal granulocytes were concordant findings. The presence of polyclonal granulocytes and lack of evidence of abnormalities in Ep-dependence or progenitor cycling were also concordant findings in most, but not all patients. Thus, normal (i.e. polyclonal) granulocytes may be produced in occasional patients in spite of the presence of a neoplastic clone. Interestingly, one third of patients thought to have ET on the basis of blood and marrow histopathology showed no abnormalities previously associated with neoplastic progenitors. These findings suggest variability in dominance of the neoplastic clone in some ET patients and the potential utility of a multifaceted laboratory approach to investigate the underlying pathology in patients with thrombocytosis. PMID- 1419803 TI - Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden. AB - Type IIB of von Willebrand's disease (vWD) is a variant in which the structurally abnormal von Willebrand factor (vWF) shows an increased affinity for the platelet vWF receptor, glycoprotein Ib (GPIb). This may sometimes give rise to platelet aggregation and thrombocytopenia in vivo. In 20 patients from nine unrelated families with type IIB vWD from Denmark, Germany and Sweden we studied the molecular defect by amplification and direct sequencing of parts of exon 28 which encode for the vWF domain that interacts with platelet GPIb. Three different point mutations were identified one of which has not previously been reported. Fifteen patients from five families were heterozygous for the Arg543-->Trp substitution. The mutation had occurred independently in all five families and in two of them represented a de novo mutation. In one of these families the father, though asymptomatic and with normal laboratory test results, carried the mutation in heterozygous form. In three families, four affected members were found to be heterozygous for the Arg543-->Cys substitution. The mutations were of different origin at least in two of the families. The third substitution, Val551-->Leu, which has not previously been described, was found in one patient and was due to a de novo mutation. In most of the patients spontaneous thrombocytopenia had been recorded on at least one occasion. Five of the patients with the Arg543-->Trp substitution and the one with the Val555-->Leu substitution had all had bleeding associated with thrombocytopenia in the neonatal period of early infancy. PMID- 1419804 TI - Defects in type IIA von Willebrand disease: a cysteine 509 to arginine substitution in the mature von Willebrand factor disrupts a disulphide loop involved in the interaction with platelet glycoprotein Ib-IX. AB - Type IIA von Willebrand disease (vWD) is characterized by the loss of high and intermediate weight multimers of von Willebrand factor (vWF) from plasma. The 3' end of exon 28 in the vWF gene from four type IIA vWD patients was amplified by the polymerase chain reaction, cloned and sequenced. Sequencing identified two potential missense mutations resulting in the amino acid substitutions Arg 834- >Gln and Glu 875-->Lys in the mature vWF subunit within an area of vWF where mutations in type IIA vWD have been reported. Neither of these amino acid substitutions was found in over 100 normal alleles tested by allele specific oligonucleotide hybridization. A polymorphism (Val 802-->Leu) was identified in another patient. Other areas of exon 28 were analysed by denaturing gradient gel electrophoresis (DGGE) and DNA from one patient demonstrated an irregular DGGE pattern on the 5' end of the exon. Sequencing demonstrated an amino acid substitution of an arginine for cysteine at position 509 adjacent to an area of vWF where defects associated with type IIB vWD have been found. This substitution was not found in 100 normal chromosomes tested by restriction enzyme digestion. The Cys 509-->Arg substitution eliminates an intramolecular disulphide bridge formed by Cys 509 and Cys 695 which is important to maintain the configuration of vWF functional domains that interact with platelet glycoprotein Ib-IX. PMID- 1419805 TI - von Willebrand disease family studies: comparison of three methods of analysis of the von Willebrand factor gene polymorphism related to a variable number tandem repeat sequence in intron 40. AB - A region with a variable number of tandem ATCT repeats (VNTR) has previously been localized within intron 40 of the von Willebrand factor (vWF) gene. In the present report we describe the use of this polymorphism as a genetic marker to study the inheritance pattern in five families affected with various types of von Willebrand disease (vWD): types I, IIA, IIB, IIC and the newly characterized variant with totally defective FVIII binding. Three means of investigation previously reported, all using polymerase chain reaction (PCR) amplification of this vWF gene region, were compared in terms of informativeness. The two direct single-step procedures analysing only partial sequences of the VNTR region turned out to be less informative (three studies informative out of five) than the third method characterizing the variability of the whole VNTR sequence. This latter approach, based on the analysis of the Alu I restriction pattern of the VNTR region, was informative in all the families investigated, therefore avoiding the need to combine it with other genetic marker studies for efficient gene tracking. In conclusion, this two-step (PCR and digestion) method is the most informative for the characterization of the inheritance of the different subtypes of vWD and for the prenatal diagnosis of its severe forms. PMID- 1419806 TI - Interaction of porcine von Willebrand factor with the platelet glycoproteins Ib and IIb/IIIa complex. AB - Porcine von Willebrand factor (PvWF) induces platelet aggregation which is thought to be responsible for the thrombocytopenia that occurs in haemophilic patients treated with commercial preparations of porcine factor VIII. This study demonstrates that such aggregation can be completely inhibited by a monoclonal antibody against human platelet glycoprotein GPIb and partially inhibited by an antibody directed against platelet GPIIb/IIIa. The interaction of PvWF with GPIb is also demonstrated by the inhibitory effect of purified glycocalycin on aggregation. The binding site of PvWF to GPIb is very close to that of human vWF, since a recombinant peptide blocks the binding of both molecules to GPIb. When platelets are incubated with PvWF, the GPIIb/IIIa receptor is activated and binds fibrinogen. PvWF also binds to GPIIb/IIIa when platelets are stimulated with thrombin, suggesting that the molecule has the same RGD sequence as other adhesive proteins (human vWF, fibrinogen, fibronectin and vitronectin). These findings identify the dual mechanisms responsible for in vivo platelet aggregation induced by PvWF, i.e. binding to GPIb and activation of the GPIIb/IIIa receptor. PMID- 1419807 TI - Patterns of development of tachyphylaxis in patients with haemophilia and von Willebrand disease after repeated doses of desmopressin (DDAVP). AB - When patients with mild haemophilia or von Willebrand disease (vWD) are repeatedly treated with desmopressin (DDAVP) at relatively short time intervals, some of them may become less responsive or unresponsive. The development of tachyphylaxis would limit the usefulness of DDAVP in clinical management of these patients. On the other hand, tachyphylaxis is not consistent, and its patterns of development are unknown. The aim of this study was to evaluate in controlled conditions the occurrence of tachyphylaxis by giving intravenous DDAVP (0.3 microgram/kg) on four consecutive days to a selected group of patients with mild haemophilia A (n = 22) and type I vWD (n = 15). After each dose, we measured parameters known to change after DDAVP, i.e. factor VIII coagulant activity, bleeding time, von Willebrand factor antigen, ristocetin cofactor and tissue-type plasminogen activator antigen. We found that on average the responses obtained after the second dose of DDAVP were approximately 30% less than those obtained after the first, but were not further reduced after the third and fourth dose. At all time intervals after DDAVP, patients with vWD responded relatively better than patients with haemophilia, and there were fewer vWD patients who responded poorly or became unresponsive. In vWD patients there were no significant changes in the bleeding time responses and in blood pressure and heart rate. The clinical implications of these findings are that repeated doses of DDAVP can be given efficaciously to many patients (particularly to those with vWD), even though responses lower than those seen after the first dose should be expected. PMID- 1419808 TI - Enhancement of human T cell responses to allogeneic stimuli by factor VIII concentrates. AB - The effect of factor VIII concentrate, from commercial and National Health Services manufacturers, on in vitro lymphocyte proliferative response to allogeneic stimulator cells was investigated. Factor VIII preparations 'purified' by ion exchange or by monoclonal antibody affinity had no effect in this assay but lymphocyte proliferation in response to allogeneic cells was markedly and consistently enhanced by some intermediate purity factor VIII concentrates and, to a lesser extent, by a factor IX preparation. These preparations did not stimulate lymphocyte proliferation in the absence of other mitogens. The co mitogenic factor(s) present in intermediate purity factor VIII was not identified. However, enhanced proliferation was not due to factor VIII itself, nor to albumin or fibronectin. The clinical relevance of the immunomodulatory activity of intermediate purity factor VIII concentrates in vitro is discussed. PMID- 1419809 TI - The production of human monoclonal antiplatelet auto-antibodies derived from human lymphocytes of normal origin: reactivity to DNA, anionic phospholipids and platelet proteins. AB - Human hybridoma monoclonal antiplatelet antibodies were produced using tonsillar lymphocytes from a nonthrombocytopenic male fused to the lymphoblastoid cell line GM 4672. Twenty of 472 (4%) IgM producing hybridomas had antiplatelet reactivity as detected by ELISA. Thirteen of these antiplatelet antibody producing hybridomas with clonality ensured by limiting dilution were tested for antigenic specificity. Two different and mutually exclusive groups of antiplatelet antibodies were identified. The first group of antiplatelet antibodies (four clones) showed reactivity that was limited to DNA and anionic phospholipids. Antibodies from the second group (seven clones) showed reactivity by immunoblotting to a variety of platelet proteins including platelet glycoprotein IIb. These antibodies did not bind DNA nor anionic phospholipids. These studies indicate that lymphocytes of normal human origin have the genetic potential to produce antiplatelet autoantibodies. These antiplatelet antibodies segregate on the basis of their target antigens into two major groups, which mimic the target antigens held responsible for antiplatelet autoantibodies in disease. These include glycoproteins (typical of chronic idiopathic thrombocytopenic purpura) and DNA and/or anionic phospholipids (typical of the lupus anticoagulant syndrome). PMID- 1419810 TI - Interleukin-2 induces activation of coagulation and fibrinolysis: resemblance to the changes seen during experimental endotoxaemia. AB - The administration of Interleukin-2 (IL-2) causes the release or generation of other cytokines such as tumour necrosis factor (TNF) which, by disturbing the anticoagulant properties of the endothelium, may induce a procoagulant state in patients receiving this drug. We therefore evaluated the effects of IL-2 on coagulation and fibrinolysis in 14 patients receiving 12 or 18 x 10(6) IU/m2/d of IL-2 given as a 15 min infusion for 5 d. Blood samples were drawn at short intervals after the first IL-2 infusion. The parameters were analysed by way of analysis for repeated measures (F tests rather than t tests). During the first day, thrombin-antithrombin (TAT) complexes started to increase 2 h after the IL-2 infusion, reaching peak levels at 4 h (n = 14; 11.2 +/- 6.4 micrograms/l v 49.8 +/- 49.2 micrograms/l, P < 0.01). Plasma alpha 2 antiplasmin (PAP) complexes showed a similar pattern rising from a mean baseline value of 17.5 +/- 7.6 nmol/l to 66.8 +/- 47.7 nmol at 4 h (P < 0.01). In four patients the peak of PAP preceeded that of TAT. Tissue plasminogen activator (tPA) rose from a mean baseline value of 4.9 +/- 3.7 micrograms/l to 26.3 +/- 13.5 micrograms/l at 4 h (P < 0.01). Plasminogen-activator-inhibitor-1 (PAI-1) levels increased from 59 +/ 35 micrograms/l to 113 +/- 39 micrograms/l at 6 h (P < 0.01). tPA PAI-1 complexes increased from 0.15 +/- 0.07 to 0.69 +/- 0.21 nmol/l at 6 h (P < 0.01). Our study indicates that IL-2 activates the coagulation and fibrinolytic systems in vivo. The changes resemble the perturbations observed after endotoxin/TNF administration. These abnormalities may play a role in the side-effects induced by IL-2 therapy. PMID- 1419811 TI - Immunophenotyping of fetal haemopoietic cells permissive for human parvovirus B19 replication in vitro. AB - Human parvovirus B19 is known to inhibit erythroid colony formation in vitro, but the precise stage of differentiation at which erythroid precursors become capable of supporting viral replication has not been accurately determined. In order to address this issue, haemopoietic cells derived from first trimester fetal liver were cultured in medium containing B19 antigen-positive serum. Infected cells were phenotyped by combining immunohistology for cell-type specific antigens with non-isotopic in situ hybridization for B19 nucleic acid. Strong nuclear hybridization signal was detected as early as 8 h after infection in erythroid precursors labelling with antibodies to glycophorin A, glycophorin C, CD43, CD36 and HLA-ABC (pronormoblast or normoblast phenotype). Giant erythroid precursors labelling with the same five antibodies were a pathognomonic feature of infected cultures, but contained relatively little B19 nucleic acid. Hybridization signal was not detected in progenitor cells of more primitive erythroid phenotype or in nuclei of cells of other lineages, though B19 DNA was occasionally localized within the cytoplasm of macrophages. Double-labelling with antibody Ki-67 confirmed that proliferating cells were targets for B19 infection. Co-detection of cell-type specific antigens and viral nucleic acid is a powerful tool for investigating host cell specificity, and suggests that proliferating late erythroid precursors are the only haemopoietic cells fully permissive for B19 infection. PMID- 1419812 TI - Treatment of advanced stage T cell lymphoblastic lymphoma: results of the United Kingdom Children's Cancer Study Group (UKCCSG) protocol 8503. AB - Ninety-five unselected patients with stage III and IV T cell lymphoblastic lymphoma were treated according to the United Kingdom Children's Cancer Study Group protocol 8503. This was a continuous, intensive leukaemia type regimen including cranial irradiation (18 Gy in 10 fractions) and continuing chemotherapy for 2 years identical to the concurrent Medical Research Council ALL protocol. Four-year event-free survival was 65% (95% CI 50-80%) with no significant difference between stage III and stage IV cases. 4.2% of patients died of infection or non-tumour related events. Following relapse salvage was unlikely without high dose chemotherapy and bone marrow rescue. These results show an improvement over previous U.K. studies but we need to continue to search for subsets of patients with resistant disease for whom even more intensive therapy possibly combined with bone marrow rescue is required. PMID- 1419813 TI - Recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma: a British National Lymphoma Investigation double-blind, placebo-controlled trial. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is active in enhancing the production of mature myeloid cells in vitro and several phase I/II clinical trials have suggested that its administration may accelerate neutrophil recovery after autologous bone marrow transplantation (ABMT). We have conducted a multicentre randomized double-blind placebo controlled trial in patients with poor prognosis malignant lymphoma receiving an identical high-dose combination chemotherapy regimen with ABMT. 61 patients were entered and 29 in each arm of the trial were evaluated. Treatment with GM-CSF did not affect the period of severe neutropenia (absolute neutrophil count (ANC) of < 0.1 x 10(9)/l) but accelerated recovery to an ANC of 0.5 x 10(9)/l (median 14 d v 20 d in controls, P = 0.001). There was no significant difference in platelet recovery between the groups (GM-CSF group platelet dependent for 25 d v control 19 d, P = NS). The number of positive blood cultures was similar in both groups (GM-CSF 14 v placebo 13) and there were no differences in days of fever > 37.5 degrees C (median 8 v 6) or days on parenteral antibiotics (11 v 10). Patients receiving GM-CSF had a median period of hospitalization following BMT of 24 d (control 25). No significant major toxicity attributable to GM-CSF administration was detected. We have confirmed in a randomized trial that GM-CSF accelerates neutrophil but not platelet recovery following ABMT. We were unable to demonstrate any accompanying changes in clinical outcome and believe that further trials are necessary to assess the clinical value of GM-CSF in BMT. PMID- 1419814 TI - Lymphoid lineage-associated features in acute myeloid leukaemia: phenotypic and genotypic correlations. AB - This study is intended to establish biological correlation between the expression of lymphoid associated features in acute myeloid leukaemia (AML). In 62 AML patients, predominantly enrolled on Eastern Cooperative Oncology Group (ECOG) treatment protocols, in whom immunoglobulin (Ig) as well as T-cell receptor beta chain (TCR-beta) gene rearrangement analyses had been performed, morphology, cytochemistry, antigen profile and karyotype were reviewed retrospectively. Nuclear reactivity with anti-TdT antibody was demonstrated in 34 patients (55%) and confirmed by ribonuclease protection assay in all patients tested. Five TdT protein negative patients were TdT-transcript positive. Lymphoid antigens (lyA) were detected in 24 of 51 cases tested (47%) with B-cell antigens (CD19, CD10) being restricted to TdT+ AML (P = 0.03). Only two patients had Ig heavy, none had Ig light chain or TCR-beta gene rearrangements. Although both patients with rearranged Ig loci were TdT+, either by protein or RNA analysis, the low incidence of such rearrangement within the TdT+ AML group (6%) argues against a significant association between the presence of TdT and crosslineage Ig gene rearrangements in AML. While FAB-diagnoses did not differ between TdT+ and TdT- or lyA+ and lyA- AML, particular immunophenotypic features correlated with TdT positively, e.g. the presence of early antigens, CD34 and HLA-DR, and the absence of the more mature myelo-monocytic antigens, CDw65 and CD14. Certain cytogenetic abnormalities were associated with TdT+ AML such as inv(16) (p13q22) or t(16;16) (p12;q22) (five patients; P = 0.03) and t(8;21) (q22;q22) (three patients). A greater number of TdT- than TdT+ AML patients had only normal karyotypes (P = 0.06). Neither immunophenotypic nor karyotypic correlations could be established for lyA+ AML. PMID- 1419815 TI - Re-emergence in remission of primary clone in acute myelogenous leukaemias with multiple chromosomal aberrations at diagnosis. AB - We describe the clinical, haematological and cytogenetic features of three patients who had acute myelogenous leukaemia (AML) with complex bone marrow karyotypes when first cytogenetically examined. Induction chemotherapy led to remission from the acute leukaemia. However, neither clinically nor morphologically did this remission mean a return to normal haematopoiesis. The two patients who displayed myelodysplastic features before and when AML was diagnosed, again developed myelodysplasia, and the third patient, who had a long history of polycythaemia vera, returned to this myeloproliferative condition. Nor was cytogenetic normalization achieved; instead, abnormal cell clones were found in which all but one of the karyotypic aberrations present at acute leukaemia diagnosis had disappeared. The solitary anomalies that were detected in these reemerging clones must correspond to the primary cytogenetic aberrations of the patients pre-leukaemic diseases. They were del(5) (q11q33) and del(17) (p11) in the two myelodysplastic cases, and der(18)t(9;18) (p11;p11) in the patient with long-standing polycythaemia vera. The other, secondary, aberrations were probably the leukaemogenic changes, and with the eradication or reduction of the subclones containing them, the leukaemic phenotype disappeared. The three cases add cytogenetic evidence to the growing understanding that the remission obtained in some AMLs is actually a return to a preleukaemic, myeloproliferative or myelodysplastic, syndrome. PMID- 1419816 TI - The selective use of AMSA following high-dose cytarabine in patients with acute myeloid leukaemia in relapse: a Leukemia Intergroup study. AB - This clinical trial was designed to evaluate the role of high-dose cytarabine (ara-C) in the treatment of adults with acute myeloid leukaemia (AML) in first relapse. We also tested the hypothesis that the selective use of AMSA (100 mg/m2/d on days 7, 8 and 9) would increase the complete remission (CR) rate when leukaemia cells remained in the bone marrow immediately following 6 d of Ara-C (2 3 g/m2/12 h) alone. Of 155 patients evaluable for response, 115 (74%) experienced marked cytoreduction by day 6 and received no further induction chemotherapy; 53 (45%) of these patients achieved CR after one course and 45 (38%) had resistant disease. The 36 patients (23%) with inadequate cytoreduction after the 6 d of ara C alone were randomly assigned either to no further chemotherapy (21 patients) or to 3 d of AMSA (15 patients). The CR rates after one course were 14% and 53%, respectively (P = 0.01), and the fractions with resistant disease were 76% and 40%, respectively. The fractional reduction of leukaemia cells in the day 6 bone marrow aspirate specimen (P < 0.0001) and the reduction in the leukaemia cell mass measured in the day 6 marrow biopsy (P = 0.001) were the strongest predictors for achieving CR versus having residual disease in univariate analyses. The median duration of remission was 5 months, but seven patients (10%) remain in CR after 30-92 + months. Among the 140 patients who received only the 6 d of ara-C, the pretreatment albumin (P = 0.002) and lactate dehydrogenase (P = 0.01) levels were the strongest predictors of response in univariate analyses, but only the albumin remained significant (P = 0.01) in a stepwise logistic regression analysis. Those patients with albumin > 4.0 mg/dl and LDH < 125% of normal had a 71% CR rate, and only 16% had resistant disease. Thus, pretreatment characteristics and rapid cytoreductin in the day 6 bone marrow sample identified a favourable subset of patients with AML in first relapse, some of whom responded quite well to 6 d of ara-C alone and have had long disease-free remissions. PMID- 1419817 TI - Primary myelodysplastic syndrome in children: the clinical experience in 33 cases. AB - We describe the clinicomorphological features in 33 cases of primary myelodysplastic syndrome classified according to the FAB classification which presented to a single centre over a 12 year period. Presenting features were typically related to pancytopenia although hepatosplenomegaly and granulocytic sarcomas were far more prevalent than in the adult population. Morphological assessment of the peripheral blood and the bone marrow showed seven patients had refractory anaemia (RA), 13 patients had RA with excess of blasts (RAEB), nine patients had RAEB in transformation (RAEB-t) and four patients had chronic myelomonocytic leukaemia (CMML). The overall mean survival was short (9.9 months) in all the subgroups and the leukaemic transformation rate was high. None of the patients scored 0-1 according to the Bournemouth Scoring System; four patients scored 2 whereas 29 patients scored 3 to 4. We conclude that unlike adults, the myelodysplastic syndromes in children run an aggressive clinical course, irrespective of the FAB subtype, and the pathogenesis of these diseases in paediatric practice warrants scientific scrutiny. Intensive chemotherapy such as the one used in de novo-AML lead to complete remission in some children and these early results suggest that this should be the treatment of choice in paediatric MDS. PMID- 1419818 TI - Low-dose etoposide: a potential therapy for myelodysplastic syndromes. AB - Four patients with refractory anaemia with excess blasts in transformation (RAEB t) and seven patients with acute leukaemia (AL) transformed from myelodysplastic syndromes (MDS) were treated with etoposide (50 mg, 2 h infusion, two to seven times per week) for at least 4 weeks. Of 10 assessable patients, three RAEB-t patients achieved partial response and one AL patient achieved complete remission. Three of the four responders were resistant to prior repeated low-dose cytarabine therapy. The responders did not require transfusions for 2-9 months while continuing on etoposide therapy. The side-effects were mild and well tolerated. Three possible mechanisms, i.e. a cytotoxic effect, differentiation induction of malignant cells, and prolongation of blood cell survival by destroying the reticuloendothelial system, may explain the effects of etoposide. We conclude that low-dose etoposide is a potential therapy for MDS and atypical leukaemia. PMID- 1419819 TI - Age-related incidence and other epidemiological aspects of myelodysplastic syndromes. AB - Although most haematologists perceive a rising prevalence and incidence of myelodysplastic syndromes (MDS), reliable epidemiological data on these disorders are largely lacking. The bone marrow register of the University of Dusseldorf allowed us to assess among other epidemiological features the incidence of MDS, which was compared to that of acute myeloid leukaemia (AML). Among a total of 18,416 different patients registered between 1975 and 1990, 584 cases of MDS (3.2%) and 506 cases of AML (2.8%) were identified. Over the study period, the percentage of newly diagnosed MDS rose from 1.3% to 4.5%, while there was no upward trend for AML. Among all patients undergoing bone marrow biopsy, the proportion of those over 60 years of age increased from 41.9% in 1975 to 54.1% in 1990. We found a strong correlation between the proportion of elderly patients and the relative frequency of MDS diagnoses. Thirty-one patients (5.3%) were classified as a secondary MDS because of previous treatment with cytotoxic chemotherapy and/or irradiation for a variety of malignancies. Twelve patients were identified in whom occupational exposure to organic solvents could not be ruled out. For calculating age-specific incidence rates, the analysis was confined to the town district of Dusseldorf (575,000 inhabitants), because exact demographical data were available for this population. In the last quinquennium of the study period (1986-90), myelodysplastic syndromes were more frequent than AML in the age group 50-70 years (4.9 v 1.8/100,000/year). In patients over 70, the incidence of MDS was more than 3 times that of AML (22.8 v 6.7/100,000). In this group, men had a higher incidence of MDS (33.9/100,000) than women (18/100,000). Crude annual incidence (all age groups) was also higher for MDS (4.1/100,000) than for AML (2.1/100,000) in recent years. We conclude that MDS are relatively common haematological neoplasias. The rising incidence in recent years is probably not due to changes in aetiological factors, but may reflect increased awareness on the part of physicians and extended use of diagnostic procedures in elderly patients. PMID- 1419820 TI - Cellular and humoral immune responses in haemophiliacs after vaccination against tick-borne encephalitis. AB - The primary immune response to a viral antigen (tick-borne encephalitis, TBE) has been determined in haemophiliacs. Twelve HIV-negative and four clinically asymptomatic, HIV-positive haemophiliacs as well as 16 age-matched healthy controls were included in the study. Antibody responses after TBE vaccination were comparable in HIV-negative haemophiliacs and controls; however, antibody titres in HIV-infected haemophiliacs were significantly lower after completion of the three-dose vaccination schedule (geometric mean reciprocal antibody titres (SEM): controls, 193 (1.37), HIV-positive haemophiliacs, 13 (2.18), P < 0.005). TBE vaccination failed to induce a T cell proliferative response in the HIV positive haemophiliacs. While in HIV-negative patients the antigen-specific lymphoproliferative responses after primary and one booster vaccination were comparable to those of the controls, cellular responses were decreased in HIV negative haemophiliacs following a second booster immunization 19 months after primary immunization (3H-thymidine incorporation, delta dpm, mean +/- SEM: controls, 34662 +/- 7129, HIV-negative haemophiliacs, 14339 +/- 7420, P < 0.005). As the protective mechanisms for TBE infection are not yet completely understood, further work will be necessary to determine whether the decreased capacity to mount a sufficient long-term cellular memory response in HIV-negative haemophiliacs might be important for the protective effect of TBE vaccination in this population. PMID- 1419821 TI - Treatment of haemophilic flexion deformities using the Flowtron intermittent compression system. AB - We have studied prospectively the use of the Flowtron intermittent compression system for the home treatment of fixed flexion deformities of elbows and knees, resulting from chronic haemophilic arthropathy. A total of 16 elbows (six unilateral and five bilateral), and 10 knees (six unilateral and two bilateral) in 11 patients were studied. Treatment caused a decrease in flexion contracture of the elbows from 41 +/- 3 degrees to 28 +/- 3 degrees (P < 0.001), an improvement of 32%. The knees showed a decrease in flexion contracture from 31 +/ 3 degrees to 20 +/- 2 degrees (P < 0.0001), an improvement of 35%. Prophylactic factor replacement was not used during the study and there were no bleeds attributable to the treatment. We conclude that the use of the Flowtron in home treatment of fixed flexion deformities in haemophiliac patients is safe, effective and cheap. PMID- 1419822 TI - Sustained correction of the bleeding time in an afibrinogenaemic patient after infusion of fresh frozen plasma. AB - We have evaluated the duration of the effect of replacement therapy with two different doses of fibrinogen on the prolonged bleeding time of an afibrinogenaemic patient and the relationship between changes in bleeding time and plasma and platelet fibrinogen concentrations. The infusion of 40 mg/kg fibrinogen, as fresh frozen plasma (FFP), corrected the prolonged bleeding time of the patient from longer that 30 min to 8 min. The bleeding time was still normal 9 d after infusion, at a time when the plasma and platelet fibrinogen levels were low (0.13 g/l and 27 micrograms/10(9) platelets; normal ranges 1.6 4.0 and 60-190). Two months later, the infusion of a smaller dose of fibrinogen (4 mg/kg) also corrected the bleeding time, which remained normal until the second day after infusion, despite the fact that plasma and platelet fibrinogen were very low (0.02 g/l and 3.4 micrograms/10(9) platelets). The bleeding time returned to the prolonged baseline values only by day 6 post-infusion, when plasma and platelet fibrinogen levels were 4 x 10(-4) g/l and 1.4 micrograms/10(9) platelets. Therefore, sustained correction of the prolonged bleeding time may be obtained in afibrinogenaemic patients with a single infusion of fibrinogen at lower doses than usually recommended. PMID- 1419823 TI - A reversed activity staining procedure for detection of an acquired antibody against factor XIII in a girl with factor XIII deficiency. AB - A new method for detection of inhibitors against factor XIII is described. Agarose gel electrophoresis with normal platelet poor plasma as a factor XIII source included in the gel was combined with reversed activity staining. The procedure was applied to a 10-year-old girl with factor XIII deficiency where substitution therapy had failed. Plasma samples from the patient inhibited the factor XIII catalysed incorporation of the fluorescent monodansylthiacadaverine into casein at a position corresponding to the migration of gamma-globulins. Treatment with Sepharose-bound protein A effectively adsorbed the factor XIII antibody in the patient's plasma. PMID- 1419824 TI - The 32.6 kb Indian delta beta-thalassaemia deletion ends in a 3.4 kb L1 element downstream of the beta-globin gene. AB - The Indian delta beta-thalassaemia, with elevated fetal gamma globin gene expression, was previously found to have a large deletion beginning 1 kb 3' of the (A) gamma globin gene at GenBank HUMHBB coordinate 42151, and extending into a new L1 sequence. We have now determined the 3' breakpoint of this deletion, and in doing so we have extended the known beta-globin gene cluster DNA sequence from its end at 73326 to projected GenBank coordinate 79016. These data show that the deletion is 32.6 kb long, terminating 11 kb 3' of the beta-globin gene. This 3' breakpoint is at 74772, within a 3.4 kb partial L1 repeat at 74263-77665; the Black ((A) gamma delta beta)(0)-thalassaemia also terminates in this L1, at 76508. In addition, two Alu sequences were found, at 73692-73816 and 78171-78441. Among the protein-binding DNA sequence motifs 3' to the Indian delta beta thalassaemia breakpoint, at 76581/76607 there is a TGATAA/ACACCC pair that binds the erythroid-specific GATA-1 and ubiquitous CACCC-box binding proteins. We hypothesize that elevated fetal haemoglobin may be due to an enhancer or enhancers 3' to the deletion breakpoints and may involve the TGATAA/ACACCC pair. PMID- 1419825 TI - Serum non-transferrin-bound iron in beta-thalassaemia major patients treated with desferrioxamine and L1. AB - Non-transferrin-bound iron (NTBI) in plasma is toxic due to its ability to participate in free radical formation with resultant peroxidation and damage to cell membranes and other biomolecules. NTBI concentration was determined in serum in 12 normal volunteers and in 52 patients with beta-thalassaemia major by a modification of the method described by Singh et al (1990). There was no detectable NTBI in normal individuals. In the patients NTBI values ranged from 1.5 to 9.0 mumol/l (mean +/- SD: 3.6 +/- 2.3). The patients' serum ferritin concentrations ranged from 207 to 11,400 micrograms/l (2674 +/- 2538), total serum iron from 20 to 61 mumol/l (39.5 +/- 9.6) and transferrin saturation from 44 to 110% (84.5 +/- 13.8). The NTBI correlated significantly with serum ferritin (r = 0.467, P < 0.001), total serum iron (r = 0.608, P < 0.001) and transferrin saturation (r = 0.481, P < 0.005). When patients were grouped according to their compliance with desferrioxamine (DFX) therapy, the good compliers had significantly lower NTBI concentrations compared to the poor compliers (poor: 5.4 +/- 1.8 mumol/l v good: 2.7 +/- 1.7 mumol/l, P < 0.001). There was also a significant difference between the level of NTBI and whether or not the patients had complications of iron overload (5.2 +/- 1.7 mumol/l v 2.9 +/- 1.6 mumol/l, P < 0.001). During this study 10 patients were entered into a trial of the oral iron chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1). Their NTBI values were observed during the first 6 months of the trial and showed a significant fall (paired t-test: P = 0.007). These results suggest that the level of NTBI may prove helpful in assessing the efficiency of chelation in patients with transfusion dependent anaemia and help to predict organ damage. PMID- 1419826 TI - Transfer of specific immunity from donor to recipient of an allogeneic bone marrow graft: evidence for donor origin of the antibody producing cells. AB - A rapid recovery of specific humoral immunity in the recipient of an allogeneic bone marrow transplantation (BMT) can be observed after immunization of the donor before graft sampling. This has been attributed to transfer of specific immunity from donor to recipient. However, to maintain the concept of transfer the origin of the antibody producing cells in the recipient after BMT must be demonstrated. To this end, donor-recipient pairs with differences in Gm-allotypes were selected and immunized before BMT with the neo-antigen Helix pomatia haemocyanin (HPH) according to three immunization protocols. Additionally, the recipients were immunized at day 42 after BMT. Serum samples were weekly obtained from the recipients in the first 100 d after BMT. The origin of HPH-specific antibody producing cells was assessed by two approaches: (1) determination of the Gm allotypes of anti-HPH antibodies within a distinct IgG subclass, (2) analysis of anti-HPH antibody spectrotypes by isoelectric focusing combined with immunoblotting. The results obtained with these two approaches show concordance in most instances and led to the conclusion that the antibody producing cells are of donor origin. PMID- 1419827 TI - Regulation of iron absorption in iron loaded subjects with end stage renal disease: effects of treatment with recombinant human erythropoietin and reduction of iron stores. AB - The effects on iron absorption of variation in erythroid activity, haemoglobin and iron stores were studied in six anaemic dialysis-dependent subjects in whom iron stores were increased from previous red cell transfusions. Gastrointestinal mucosal uptake and whole body retention of oral iron were measured at the beginning of the study, after starting treatment with recombinant erythropoietin (but before significant increase in haemoglobin), after partial correction of anaemia, after further reduction of iron stores by repeated phlebotomy, and when erythropoiesis decreased from the discontinuation of treatment with erythropoietin. Between successive measurements, valid comparisons were made in five subjects. Correction of anaemia decreased whole body retention of iron through decreased mucosal uptake (P = 0.032). Further reduction in iron stores through repeated phlebotomy whilst the increase in haemoglobin was maintained by treatment with erythropoietin, tended to increase whole body retention of iron through an increase in mucosal transfer (P = 0.010). With initial enhancement of erythropoiesis in anaemic iron-loaded subjects there was no change in any measured component of iron absorption. However, after correction of anaemia and reduction of iron stores, a decrease in erythropoiesis was associated with decreased whole body iron retention in all subjects through decreased mucosal transfer (P = 0.028). The data suggest that anaemia upregulates mucosal iron uptake, and that erythroid activity upregulates mucosal transfer but that this latter effect may be counter-balanced by iron overload which downregulates mucosal transfer. PMID- 1419828 TI - Transferrin uptake by bone marrow macrophages is independent of the degree of iron saturation. AB - The uptake of transferrin by macrophages was studied in relation to the degree of iron saturation. Rat bone marrow derived macrophages were incubated with transferrin labelled with 59Fe and 3H. At 37 degrees C the amount of 59Fe incorporated by macrophages was dependent on the time of incubation. 3H labelled transferrin was found degraded in the supernatants of the cell culture (material not precipitated by trichloroacetic acid) in a time dependent fashion. Taking into account the specific activity of 59Fe-3H labelled transferrin, we found that 95% of the transferrin uptake was degraded. This suggests that most of the uptake of transferrin was not mediated by a receptor-dependent mechanism, but by a phase fluid endocytosis. 3H-labelled apotransferrin appears in the supernatant of the cell culture at the same rate as 59Fe-3H labelled diferric transferrin, showing an identical uptake for the two types of transferrin. Uptake of apo- or diferric transferrin by macrophages was identical in relation to time of incubation and the amount of transferrin used. These studies suggest that most of the transferrin uptake by bone marrow macrophages (non-activated or non-elicited cells) is mediated by a non-receptor mechanism that is independent of the degree of transferrin saturation. PMID- 1419830 TI - Towards a new predictor of AIDS progression through the quantitation of HIV-1 DNA copies by PCR in HIV-infected individuals. AB - The proviral copy (PVC) number in peripheral blood mononuclear cells (PBMCs) of human immunodeficiency virus (HIV)-infected individuals was measured by a quantitative polymerase chain reaction (PCR) assay to determine over time the relation between the viral load and the evolution towards the disease in HIV infected people: 67 anti-HIV-1 positive individuals (60 stage II/III, 7 stage IV) were studied. The mean PVC number per 1.5 x 10(5) PBMCs in stage II/III individuals (14.4 +/- 14.2) and in stage IV individuals (32.2 +/- 22.9) was significantly different (P < 0.02). PVC number was inversely correlated to the CD4 lymphocyte count (P < 0.01). In the logistic regression, the PVC number was a better marker of evolution towards the disease than the CD4 lymphocyte count. The mean proportion of HIV-infected PBMCs in stage IV individuals and in stage II/III individuals was 1/4606 and 1/10714, respectively. PMID- 1419829 TI - Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion dependent thalassaemia: Indian trial. AB - From August 1989 to May 1991, 52 patients with transfusion dependent thalassaemia major received L1 (1,2-dimethyl-3- hydroxypyrid-4-one), the oral iron chelator, for a period of 3-21 months (mean +/- SD: 14.2 +/- 6.8). Mean (+/- SD) urinary iron excretion varied from 6.2 +/- 4.6 mg/d on 25 mg/kg/d of L1 to 42.3 +/- 37.1 mg/d on 100 mg/kg/d of L1. Mean (+/- SD) drop in S ferritin was 1465 +/- 990 micrograms/l after 5.0 +/- 0.8 months to 3641.2 +/- 2299.3 micrograms/l after 20.1 +/- 0.9 months of therapy. There was no evidence of neutropenia, thrombocytopenia, ear or eye toxicity. L1-related arthralgia, which was reversible on dose reduction or stoppage, was seen in 20 patients (38.5%), while minor gastrointestinal (GI) tract symptoms occurred in seven (3.5%) cases. We conclude that although L1 is an effective iron chelator, further studies are required to understand the mechanism of L1 related arthralgia and also to find a safer but effective dose on which incidence of L1 related arthralgia is minimal. PMID- 1419831 TI - Therapy with recombinant interferon alpha-2c during unexpected pregnancy in a patient with chronic myeloid leukaemia. PMID- 1419832 TI - Translocation (3;21) (q26.2;q22.1) found in a patient with myelodysplastic syndrome and long-term exposure to organic solvents. PMID- 1419833 TI - Transient plasmacytosis with acute infection in myeloma. PMID- 1419834 TI - Myelodysplastic syndrome associated with increased bone marrow fibrosis and translocation (5;12)(q33;p12.3). PMID- 1419835 TI - Spontaneous regression of Ki-1 positive T-cell non-Hodgkin's lymphoma in a patient with HIV infection. PMID- 1419836 TI - Splenectomy and chronic ITP in children. PMID- 1419837 TI - Childhood meningiomas. Experience in the modern imaging era. AB - Twenty children with meningiomas (ages 18 months to 17 years) received initial therapy at the Children's Hospital of Philadelphia between January 1975 and June 1991, accounting for 2% of children with primary brain tumors seen during that time interval. All were verified histopathologically, and none had had prior irradiation. Fifteen were male and 5 female. Fifteen tumors were intracranial, all located supratentorially. Two of these also had a component within the optic canal. One tumor was entirely within the orbit. Four meningiomas arose within the spinal canal. Associated conditions were neurofibromatosis (NF) type I (1 patient), NF type II (2 patients), and a facial alveolar rhabdomyosarcoma (1 patient). A gross total resection as documented by postoperative scan and operative note was accomplished in 12 patients. Four of these relapsed, at a mean of 3.5 years from initial surgery. In 4 patients a near-total resection (> 90%) was performed. Of these, 2 progressed at 9 months and 1.5 years. One of these died of complications associated with reoperation. In 4 patients a partial resection (50-90%) was performed. Two of these progressed at 4 months and 1 year, and the other 2 have been followed for less than 2 years. Five patients received radiation therapy (RT). One patient received RT as adjunctive therapy after primary surgery because of papillary histology. The other 4 had RT following reoperation for recurrence at a mean of 1.5 years from diagnosis (range, 7 months to 2 years). These 4 patients remain alive and with stable disease at a mean of 6 years from diagnosis (range 2-8.8 years).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419838 TI - Specialization is inevitable. PMID- 1419839 TI - Craniovertebral abnormalities in Down's syndrome. AB - The ligamentous laxity associated with atlantoaxial subluxation has been assumed as a normal occurrence in 15-20% of Down's syndrome patients. The occipitoatlantoaxial instability that accompanies this entity has been poorly recognized. The medical records and radiographic findings of 18 symptomatic patients with Down's syndrome and cervicomedullary compromise were reviewed (1979 1991). All patients were evaluated prospectively under protocol for abnormalities of the cranial vertebral junction. There were 11 males and 7 females (age 3-42). 'Fixed' atlantoaxial luxation was seen in 8 (5 developed precipitous onset of cervical medullary compression). Occipitoatlantoaxial instability was present in 9 and associated rotary luxation in 9. The average predental space was 8 mm in the neutral position in 18 individuals. Two adolescents had previously undergone atlantoaxial dorsal fusion with subsequent progressive basilar invagination due to unrecognized occipitoatlantal instability. An os odontoideum was seen in 3 patients. Irreducible invagination in 2 was treated with anterior decompression followed by dorsal occipital cervical fixation. The occipital cervical fixation was utilized in 10 individuals. Atlantoaxial dorsal fusion was made in 7 and 2 patients with acute rotary luxation of C1 and C2 were treated with immobilization. Halo immobilization in two individuals following a dorsal occipital cervical fixation produced an anterior fusion at the cranial vertebral complex indicating active vertebral ligamentous pathology. The review focuses on increased incidence of occiput cervical instability in the spectrum of craniovertebral junction abnormalities associated with Down's syndrome. A large percentage has an odontoid ossicle probably as a result of repeated minor trauma. The results of surgical stabilization have been shown to be excellent. PMID- 1419841 TI - Complications with selective posterior rhizotomy. AB - Since 1986 250 patients have undergone selective posterior rhizotomy for spastic cerebral palsy at New York University Medical Center. Severe, perioperative complications were experienced by 15% of these patients and consisted of bronchospasm, aspiration pneumonia, urinary retention, ileus, sensory loss. Additionally, most of our patients had severe pain immediately after the surgery and nearly half had dysesthesias for up to 3 weeks. Long-term complications such as decreasing range of muscle movement and hip dislocation are now becoming apparent. This patient population must be viewed as having special risks attendant with surgery and particularly with selective posterior rhizotomy. PMID- 1419840 TI - Selective functional posterior rhizotomy for treatment of spastic cerebral palsy in children. Review of 50 consecutive cases. AB - Fifty consecutive children are described with spastic cerebral palsy treated with selective functional lumbar and sacral rhizotomy and followed for a minimum of 6 months. In all patients, spasticity improved postoperatively, but this was not necessarily accompanied by a functional improvement. Eighteen children who could not walk preoperatively were able to do so after rhizotomy. All 17 children who could walk preoperatively could do so following surgery, and in 15, gait was improved. Complications included transient urinary dysfunction in 4 children and sensory loss in 1. The operative procedure evolved with time: the technique of replacement laminotomy was refined; the electrophysiologic basis for selection of nerve rootlets changed after studies of nonspastic controls; smaller percentages of the L3 and L4 roots were sectioned in an attempt to prevent postoperative weakness of quadriceps, and there was a trend in the most recent patients to cut a smaller portion of all the posterior roots. PMID- 1419842 TI - Fluid, blood, and blood product management in the craniofacial patient. AB - This report is a retrospective review of the perioperative management of 56 children who underwent craniofacial surgical procedures. The use of a combination of 5% dextrose in normal saline or 5% dextrose in Ringer's lactate and normal saline resulted in postoperative sodium values in a normal range. In patients receiving a combination of 5% dextrose and electrolyte No. 48 and normal saline, the mean postoperative sodium level was 130 mEq/l with 9 of 18 patients below 130 mEq/l. Two patients in the series suffered clinical seizures on postoperative day 1 as a result of serum sodium levels of 122 and 121 mEq/l, respectively. We recommend that only solutions with a sodium content between 77 and 154 mEq/l be used routinely in the perioperative management of craniofacial patients. PMID- 1419843 TI - Neuroimaging for investigation of seizures in children. AB - In patients with structural abnormalities of the brain with poor seizure control by medication, epilepsy surgery becomes a very important tool for seizure control. Numerous radiological imaging studies are being used for studying the abnormality in order to aid in the planning of surgery. Included in the radiological imaging modalities are CT, MR, and Xenon CT, SPECT and PET. In future, perfusion and diffusion MR as well as MEG mapping will become part of the investigative tool. The following paper is a summary and discussion of the usefulness of different modalities in different disease entities with a proposal for the method of investigation. PMID- 1419844 TI - Magnetic resonance imaging of pediatric posterior fossa tumors. AB - MR detected abnormality in all 115 pediatric patients who subsequently had pathologically proven posterior fossa tumors. In 114, the initial magnetic resonance (MR) diagnosis was that of brain tumor. In 1, with less than 1-cm2 area of gadolinium enhancement, the significance of the initial finding was uncertain. Common posterior fossa tumor subgroups (brainstem gliomas, cerebellar astrocytomas, primitive neuroectodermal tumors, and ependymomas) have relatively consistent presentations on imaging studies. However, less common tumors mimic the MR appearance of more common ones, while common tumors may also have atypical appearances. PMID- 1419845 TI - Applications of neuroimaging in hydrocephalus. AB - Hydrocephalus is a common problem in pediatric neurological and neurosurgical practices. In this manuscript, the common imaging appearances of hydrocephalus are discussed in relation to the underlying causes of the hydrocephalus. Moreover, specific findings seen on magnetic resonance imaging (MR) examinations are discussed and contrasted with those on computed x-ray tomography (CT) and ultrasound. Finally the imaging findings associated with treatment of hydrocephalus are discussed. In particular, analysis of shunt function, the diagnosis of shunt failure, and the complications of shunting are stressed. PMID- 1419847 TI - Neuroradiology of intracranial infection. AB - The ability to detect and differentiate intracranial infection has markedly improved, first with the introduction of computed tomography and, more recently, with magnetic resonance. Enhanced magnetic resonance imaging is the procedure of choice in the evaluation of nearly all intracranial infections. The sensitivity of MR to foci of increased water content, seen in most parenchymal infections, the lack of bone artifact, and the multiplanar capability of MR have led to this preeminence. Computed tomography remains useful primarily in those infections associated with intracranial calcification, such as TORCH syndrome. This article summarizes the most recent CT and MR findings of infection involving the meninges and brain parenchyma. PMID- 1419846 TI - Intraoperative uses of ultrasound in the pediatric neurosurgical patient. AB - Ultrasound imaging has become a common method for intraoperative evaluation of the central nervous system. Real-time monitoring aids in guidance for aspiration of fluid collections and placement of catheters as well as the localization and evaluation of masses, and confirmation of their complete removal. Color Doppler is useful in the evaluation of blood flow in arteriovenous malformations, aneurysms, and neoplasms. Consultation among the ultrasound staff, neuroradiologists, and neurosurgeons before the operative procedure maximizes the usefulness of ultrasound, thus aiding in the success of surgery. PMID- 1419848 TI - Characterization of genes expressed in mesophyll protoplasts of Nicotiana sylvestris before the re-initiation of the DNA replicational activity. AB - To decipher the early events preceding the re-entry of somatic cells into the cell cycle, we constructed a cDNA library from 6-h-old protoplasts of Nicotiana sylvestris. We characterized three mRNAs, via their cDNAs, that accumulate at very high levels 6 h after the beginning of the culture. Two of them could be identified by comparison of the deduced amino acid sequence to databanks. 6P10 is a novel type I trypsin inhibitor, which has the peculiarity of being devoid of the pro-sequence peptide described to be essential for transport to the vacuole. 6P73 is a novel, moderately anionic peroxidase. 6P50 belongs to a gene family not yet identified. These genes are highly expressed in protoplasts at the beginning of the culture and moderately in roots, but are neither expressed in response to chemical treatment, heat shock, pathogen attacks nor during tumor induction. These findings suggest that the activation of these genes corresponds not only to a specific adaptation of protoplasts to the new environment but also, since their level of expression decreases at the onset of division, to a sequence of events connected with the establishment of the new program of gene expression of the dividing cell. PMID- 1419849 TI - Suramin changes the fate of Spemann's organizer and prevents neural induction in Xenopus laevis. AB - Suramin, a polyanionic compound, which has previously shown to dissociate platelet derived growth factor (PDGF) from its receptor, prevents the differentiation of neural (brain) structures of recombinants of dorsal blastopore lip (Spemann's organizer) and competent neuroectoderm. Furthermore, the suramin treatment changes the prospective differentiation pattern of isolated blastopore lip. While untreated dorsal blastopore lip will differentiate into dorsal mesodermal structures (notochord and somites), suramin treated dorsal blastopore lip will form ventral mesoderm structures, especially heart structures. The results are discussed in the context of the current opinion about the mode of action of different growth factor superfamilies. PMID- 1419850 TI - Hairless, a Drosophila gene involved in neural development, encodes a novel, serine rich protein. AB - Hairless is a dominant loss of function mutation in Drosophila affecting the formation of adult sensory organs. In the mutants, neuronal precursor cells do not differentiate, suggesting that Hairless might be involved in specifying or realizing neuronal fate in the fly, similar to the 'pro-neural' genes of the achaete-scute complex. As highlighted by the manifold phenotypic interactions of Hairless with most of the neurogenic loci, the gene might play an important role in nervous system development. Therefore, we initiated a molecular analysis of the Hairless locus in order to elucidate the function of its gene product and gain insight into the biochemical nature of the observed genetic interactions in which it participates. Here, we report the molecular cloning of the Hairless locus, confirmed by breakpoint and transformation analysis. Unexpectedly, Hairless activity peaks during embryogenesis, where transcripts accumulate primarily in endo- and mesodermal cell layers, and is lowest during larval stages, the lethal phase of Hairless mutants. The putative Hairless protein deduced from DNA sequencing is extremely basic and highly enriched in serine residues. Hairless appears to encode a novel protein without compelling homology to other known proteins which function in specifying peripheral nervous system development in Drosophila. PMID- 1419851 TI - Transforming growth factor-beta 1 in heart development. AB - Defined biochemical stimuli regulating neonatal ventricular myocyte (cardiomyocyte) development have not been established. Since cardiomyocytes stop proliferating during the first 3-5 days of age in the rodent, locally generated 'anti-proliferative' and/or differentiation signals can be hypothesized. The transforming growth factor-beta (TGF-beta) family of peptides are multifunctional regulators of proliferation and differentiation of many different cell types. We have determined in neonatal and maturing rat hearts that TGF-beta 1 gene expression occurs in pups of both normotensive (Wistar Kyoto, WKY) and hypertrophy-prone rats (spontaneously hypertensive, SHR). TGF-beta 1 transcript levels were readily apparent in total ventricular RNA from SHR pups within 1 day of age and elevated in 3-7 day old WKY and SHR hearts when cardiomyocyte proliferation indices are diminished. TGF-beta 1 transcript levels remain at a 'relatively' high level throughout maturation and into adulthood in both strains. Further, TGF-beta 1 transcripts were localized to cardiomyocytes of neonatal rat ventricular tissue sections by in situ hybridization. Immunoreactive TGF-beta was co-localized to the intracellular compartment of neonatal cardiomyocytes at the light and electron microscopic level. In vitro analysis using primary cultures of fetal and neonatal cardiomyocytes indicated that TGF-beta s inhibit mitogen stimulated DNA synthesis and thymidine incorporation. From these data, we propose that locally generated TGF-beta s may act as autocrine and/or paracrine regulators of cardiomyocyte proliferation and differentiation as intrinsic components of a multifaceted biochemical regulatory process governing heart development. PMID- 1419852 TI - Intracellular signalling pathways involved in mesoderm induction by FGF. AB - We have examined the possible role of two signal transducing mechanisms, tyrosine phosphorylation and activation of protein kinase C (PKC), during fibroblast growth factor (FGF)-induced mesoderm induction in Xenopus. Tyrosine phosphorylation was examined through the use of a monoclonal anti-phosphotyrosine antibody. This antibody was shown to recognize the FGF receptor crosslinked to radioiodinated FGF. We also studied the response of Xenopus ectodermal explants to sodium orthovanadate, a compound that has been shown to elevate intracellular phosphotyrosine levels. Thirty percent of explants cultured in 100 microM vanadate were induced. In addition, vanadate synergized with FGF to give inductions that were more dorsal in nature than either vanadate or FGF alone. The role of PKC was evaluated by measuring PKC activity during mesoderm induction by FGF and by examining the effect of the phorbol ester 12-O-tetradecanoylphorbol 13 acetate (TPA) on explants. TPA did not induce mesoderm, however, activation of PKC was detected in FGF-treated explants. Therefore, activation of the PKC pathway alone is not sufficient for mesoderm induction. Simultaneous treatment with TPA and FGF resulted in a significant inhibition of mesoderm induction by FGF, suggesting that activation of PKC could be part of a negative feedback mechanism. In contrast, TPA had no effect on induction by activin A. PMID- 1419853 TI - Certified sick leave as a non-specific morbidity indicator: a case-referent study among nurses. AB - A case-referent study assessed the association between medically certified sick leave from work and some occupational characteristics--namely, two work load indices (nurse patient ratio and patients' average duration of stay) and hospital and care unit. Study participants were nurses from seven general hospitals in Quebec City who had been employed for at least six months at the time of study. Cases (n = 184) experienced at least one episode of medically certified sick leave for a diagnosis "most likely to be related to work load" between 1 January 1984 and 31 May 1987. Referents (n = 1165) were chosen from subjects who had no such leave, whatever the medical reason, and were matched to cases by the incidence density sampling method. Occupational data were collected from employment records and administrative files. Analysis was by multiple logistic regression. Significant associations were found between sick leave and nurse patient ratio among head nurses, patient's duration of stay, and one hospital. Sick leave was more frequent among full time permanent nurses and among those on night and evening schedules. These associations were independent of age, duration of service in this hospital or in the actual job assignment, and care unit. This study supports the relevance of using sick leave as a non-specific indicator of health out-comes. PMID- 1419854 TI - Subclinical impairment of colour vision among workers exposed to styrene. AB - The effects of exposure to styrene were studied among 60 men aged 20 to 56 (mean 29.5) employed in shipbuilding. Exposure was due to the handling of glass reinforced polyester materials. The study was cross sectional and the workers were compared with a control group matched for age, social and occupational state, and ethnic origin. During the study, the mean atmospheric exposure to styrene was 24.3 ppm. Mean urinary elimination was 230 mg/g creatinine for mandelic acid and 57.4 mg/g creatinine for phenylglyoxylic acid. The Farnsworth 100 hue test showed no significant differences between the exposed and control groups for error scores. A significant difference was found, however, for the number of subjects with errors axis in the red-green, or blue-yellow ranges, or both, which was larger among the exposed workers (32/60 v 20/60 for the controls (p < 0.05)). Psychometric tests were also conducted, using the World Health Organisation (WHO) neurobehavioural core test battery. Of the seven tests it included, anomalies were only found for the aiming test. These results suggest that exposure to moderate styrene concentrations of the order of 25 ppm can lead to impairment of colour vision. PMID- 1419855 TI - Musculoskeletal symptoms and type A behaviour in blue collar workers. AB - OBJECTIVE: Type A behaviour pattern, characterised by excessive competitiveness, impatience, hostility and time urgency, has been previously investigated as a risk factor for coronary heart disease. There are few studies concerning musculoskeletal symptoms and type A behaviour. Could there be a higher frequency of musculoskeletal symptoms with a more pronounced type A behaviour? DESIGN: A cross sectional retrospective study. Standardised nordic questionnaires were used for the analysis of musculoskeletal symptoms and the Bortner questionnaire and its subscales (1) speed and (2) hard driving and competitiveness were used to assess type A behaviour. SETTING: Factory based (a manufacturing industry where they make ventilating shafts). SUBJECTS: 58 blue collar workers (51 men and seven women). Mean age was 36.9 years. Mean employment time was seven years. MAIN OUTCOME MEASURE: Blue collar workers with musculoskeletal symptoms had a more pronounced type A behaviour than those without symptoms. RESULTS: For shoulder symptoms during the past 12 months blue collar workers had a more pronounced type A behaviour (p < 0.001). For symptoms during the past seven days the results were significant for the neck (p < 0.01), the shoulder (p < 0.01), and also for lower back pain (p < 0.05). There were no differences in age, psychosocial factors, or psychosomatic symptoms. According to the Bortner subscales, the speed subscale seems to be more important than the hard driving and competitiveness subscales. CONCLUSIONS: Blue collar workers with a more pronounced type A behaviour seem to have a higher incidence of musculoskeletal symptoms. PMID- 1419856 TI - Objective testing for vasospasm in the hand-arm vibration syndrome. AB - Since vibration white finger (VWF) became a prescribed industrial disease in 1985, objective testing for the diagnosis and grading of the severity of the condition has become desirable. Measurements have been made of finger blood flow and finger systolic pressure before and after cold challenge in 22 healthy control subjects and 34 men presenting for medical examination in connection with compensation claims for VWF. This type of testing has previously produced one false negative result in 35 patients with an established clinical diagnosis of Raynaud's syndrome and no false positives in 40 control subjects. Finger blood flow was not significantly different in the claimants and controls in either warm or cool environments at local finger temperatures from 32 degrees C down to 20 degrees C. Finger systolic pressure in the claimants was not significantly different from that in the controls when the fingers were warm at 32 degrees C. After five minutes middle phalangeal cooling to 15 or 10 degrees C, finger systolic pressure was 0 mm Hg in 22 of the claimants indicating that vasospasm had occurred. No vasospasm occurred in the remaining 12 claimants or in any of the 22 control subjects. By clinical assessment alone, 26 of the 34 claimants had been thought to have VWF and 21 (81%) of these exhibited vasospasm in the laboratory. Of the eight considered not to have VWF, only one exhibited vasospasm in the laboratory. PMID- 1419857 TI - Fatal accidents among Icelandic seamen: 1966-86. AB - OBJECTIVE: To investigate whether fatal accidents, including drownings, have decreased among Icelandic fishermen and seamen. DESIGN: Historical prospective study. The study population was record linked with the National Register and the Register of Deceased to get information on water transport accidents (ICD-7, E850 E858) during the period 1966-86. The number of persons in each calendar year and the number of days at sea registered at the pension fund were both used as denominator to find annual mortalities. SETTING: Iceland. SUBJECTS: 27,884 seamen who were members of the Seamen's Pension Fund. The cohort included both fishermen and seamen from the merchant fleet. MAIN OUTCOME MEASURES: Changes in mortality from all accidents and drownings from 1966-86. RESULTS: The mortality for all fatal accidents was 89.4 per 10(5) person-years and did not change appreciably during the study period. The mortality for drowning was unchanged at 73.2 per 10(5) person-years. The greatest number of drownings were among those 20-24 years of age but the mortality for drowning was highest among those 45-54 years of age. CONCLUSION: Mortality because of fatal accidents and drownings among these seamen was high and did not conclusively decrease during the study period. Further preventive measures are needed. PMID- 1419858 TI - Concentrations of individual serum or plasma bile acids in workers exposed to chlorinated aliphatic hydrocarbons. AB - Individual serum or plasma bile acid concentrations were measured by high performance liquid chromatography in two groups of workers with differing exposures: to hexachlorobutadiene (HCBD) and a mixture of other chlorinated solvents (SOLVENT) in study A; and trichloroethylene (TCE) in study B. Exposures to HCBD and TCE were associated with highly significant increases in a number of individual and summed bile acid measures, with a dose effect relation shown for HCBD. Exposure to SOLVENT was associated with significant decreases in three bile acid measures but this may have been due to misclassification of exposure. No association was found between any of the exposures and any of the standard tests of liver function. This preliminary study suggests that some chlorinated hydrocarbons are associated with raised bile acid concentrations in the blood of exposed workers. It may be that the changes in such concentrations reflect early and small disturbances of liver function. The significance and mechanism of the changes are yet to be determined. PMID- 1419859 TI - Dose related acute irritant symptom responses to occupational exposure to sodium borate dusts. AB - A repeated measurement design was employed in the study of acute symptoms of eye and respiratory tract irritation resulting from occupational exposure to sodium borate dusts. The symptom assessment of the 79 exposed and 27 unexposed subjects comprised interviews before the shift began and then at regular hourly intervals for the next six hours of the shift, four days in a row. Exposures were monitored concurrently with a personal real time aerosol monitor. Two different exposure profiles, a daily average and short term (15 minute) average, were used in the analysis. Exposure-response relations were evaluated by linking incidence rates for each symptom with categories of exposure. Acute incidence rates for nasal, eye, and throat irritation, and coughing and breathlessness were found to be associated with increased exposure levels of both exposure indices. Steeper exposure-response slopes were seen when short term exposure concentrations were used. Results from multivariate logistic regression analysis suggest that current smokers tended to be less sensitive to the exposure to airborne sodium borate dust. There was no indication that anhydrous sodium borate was more potent than the other sodium borates in this work environment. PMID- 1419860 TI - Pulmonary effects of exposure to fine fibreglass: irregular opacities and small airways obstruction. AB - OBJECTIVE: Man made mineral fibres imitate asbestos and produce tumours of the pleura in animals. To answer the question, Does prolonged exposure to fibreglass adversely affect pulmonary function or produce radiographic abnormalities in human subjects? we studied workers in a midwestern appliance plant where refrigerator doors and previously entire cabinets were insulated with fibreglass sheeting and loose rotary spun fibreglass. METHODS: Spirometry and lung volumes were measured, respiratory and occupational questionnaires were administered, and chest x-ray films were read for pneumoconiosis using International Labour Office (ILO) 1980 criteria in 284 workers with exposure of 20 years or more. RESULTS: Expiratory flows were reduced including FEV1 (mean 90.3% of predicted (pr), FEF25 75 (85.5% pr), and FEF75-85 (76.2% pr). Forced vital capacity was significantly reduced (92.8% pr) and total lung capacity was significantly increased (109.2% pr). In white male smokers, a group large enough for comparisons, parameters of pulmonary function were reduced further in the presence of irregular opacities. Forty three workers (15.1%) had evidence of pneumoconiosis on chest radiographs: 26 of these (9.1%), had no known exposure to asbestos and 17 (6.0%) had some exposure. The best judgement was that in 36 (13.0%), pulmonary opacities or pleural abnormalities were due to fibreglass. CONCLUSION: Commercial rotary spun fibreglass used for insulating appliances appears to produce human disease that is similar to asbestosis. PMID- 1419861 TI - Lung cancer and occupation: results of a multicentre case-control study. AB - The objective of the current study was to estimate the risk of lung cancer attributable to occupational factors and not due to tobacco. At 24 hospitals in nine metropolitan areas in the United States, 1793 male lung cancer cases were matched for race, age, hospital, year of interview, and cigarette smoking (never smoker, ex-smoker, smoker (1-19 and > or = 20 cigarettes per day)) to two types of controls (cancer and non-cancer hospital patients). Information on usual occupation, exposure to specific potential carcinogens, and cigarette smoking was obtained by interview. Risk of lung cancer was increased significantly for electricians; sheetmetal workers and tinsmiths; bookbinders and related printing trade workers; cranemen, derrickmen, and hoistmen; moulders, heat treaters, annealers and other heated metal workers; and construction labourers. All of these occupations are potentially exposed to known carcinogens. Odds ratios (ORs) were increased for exposure to coal dust (adjusted OR = 1.5; 95% confidence interval (95% CI) 1.1-2.1). After stratification, this association was statistically significant only after 10 or more years of exposure. Lung cancer was also related to exposure to asbestos (adjusted OR = 1.8; 95% CI 1.5-2.2). The ORs increased with increasing duration of exposure to asbestos for all smoking categories except for current smokers of 1-19 cigarettes per day. The statistical power to detect ORs among occupations that were previously reported to be at increased risk of lung cancer but that failed to show an OR of at least 1.5 in the current study was small. The cumulative population attributable risk (PAR) of lung cancer due to occupation was 9.2%. It is concluded that occupational factors play an important part in the development of lung cancer independently of cigarette smoking. Because occupations at high risk of lung cancer were under represented, the cumulative PAR of the present study is likely to be an underestimate of the true contribution of occupation to risk of lung cancer. PMID- 1419863 TI - Survival of asbestos insulation workers with mesothelioma. AB - Malignant mesothelioma is a lethal disease. It is rare in the general population; however, workers exposed to asbestos suffer significant burdens of the neoplasm. The survival time of 457 consecutive fatal cases of pleural and peritoneal mesothelioma that occurred among 17,800 asbestos insulation workers observed prospectively from 1 January 1967 to 1 January 1987 was studied. Mean survival time from initial presentation of the disease to death was 11.4 months for the pleural mesothelioma patients compared with 7.4 months for the peritoneal group. This difference was statistically significant. Mean survival time from diagnosis to death was shorter for both groups of patients: 8.4 months for pleural mesothelioma v 5.8 months for the peritoneal cases. In conclusion, survival time in mesothelioma patients is short; most die within a year from the onset of the initial symptoms. No effective therapy is yet available. PMID- 1419862 TI - Malignant melanoma of the skin among workers in a telecommunications industry: mortality study 1976-83. AB - An incidence study of malignant melanoma of the skin (MMS), conducted previously among the workers of four plants of a large telecommunications industry located in Montreal, Canada, showed a standardised incidence ratio of 2.7 (95% confidence interval (95% CI) 1.3-5.02) for the years 1976 to 1983. To describe more precisely the magnitude of the problem a mortality study was started among the same population (n = 9590) for the same period (1976-83). At the end of 1983, 9180 workers were alive, 261 were dead, and 149 (1.5%) were not traced. Standardised mortality ratios (SMRs) for all causes of death were surprisingly low for men (SMR = 0.57; 95% CI 0.50-0.64) and women (SMR = 0.56; 95% CI 0.37 0.82). The SMRs for major causes of death were also less than expected. These results may be explained by a pronounced selection bias (healthy worker effect) and by the short duration of follow up (eight years). For MMS, two deaths occurred among men (SMR = 2.00; 95% CI 0.24-7.22) and one among women (SMR = 4.81; 95% CI 0.12-26.78). A third man who died of MMS was miscoded as having a primary pulmonary melanoma. Including this case increased the SMR for MMS to 3.00 (95% CI 0.62-8.77; p = 0.08). Polyvinyl chloride and polychlorinated biphenyls were used in the plants and some of the workers did soldering. A planned case control study will investigate other possible exposures at work. PMID- 1419864 TI - Follow up study of renal tubular dysfunction and mortality in residents of an area polluted with cadmium. AB - A retrospective cohort study was conducted to investigate the association between cadmium induced renal tubular dysfunction and mortality. A total of 230 subjects aged 40 or older and living in a cadmium polluted area in Kosaka Town, Akita Prefecture, Japan, were studied at least once between 1975 and 1977 and again in 1990. Urinary beta 2-microglobulin and total amino nitrogen concentrations were significantly related to mortality from all causes in women. The finding supports the idea that cadmium induced kidney damage is a factor associated with mortality in a general population exposed to environmental cadmium. PMID- 1419865 TI - Chronic glomerulonephritis and exposure to solvents: a case-referent study. AB - To evaluate the risk of chronic glomerulonephritis in subjects exposed to solvent vapours, a case-referent study was carried out. The case group, including 60 patients (44 men and 16 women) with non-systemic chronic glomerulonephritis, established by biopsy, was compared with 120 control subjects (60 patients with traumatic fractures and 60 patients affected by nephrolithiasis) matched by sex and age. Information on occupational and non-occupational exposure to solvent was obtained by questionnaire. The exposure scores drawn from questionnaires were significantly higher in the case group than in the referent groups for both total and occupational solvent exposure. No significant differences in non-occupational exposure were found. The odds ratio of chronic glomerulonephritis for occupationally exposed (score > 0) was 3.9 (95% confidence interval (95% CI) 1.64 8.33). When IgA nephropathy patients (n = 27) were separately evaluated, an increased risk was found for both total and occupational exposure. Using a logistic regression model, a dose-response effect for occupational exposure was seen. The results support the hypothesis that chronic glomerulonephritis may be related to environmental factors such as exposure to hydrocarbons. PMID- 1419866 TI - Lipid oxidation and atherosclerosis: a possible vindication of fresh eggs and milk. PMID- 1419867 TI - Baroreflex responses to the stress of severe hemorrhage in the rat. AB - In two groups of anesthetized (sodium pentobarbital), mature Sprague-Dawley rats, 1) aged 2 years and weighing 300-400 grams, 2) aged 6 months weighing 200-300 grams, baroreflex-induced circulatory responses to pressor (graded doses phenylephrine) and depressor (graded doses nitroglycerine) agents were compared to those occurring during progressive hemorrhage in the same animals. Graded withdrawals of blood from the femoral artery elicited progressive hypotension accompanied by bradycardia rather than expected tachycardia. Graded doses of phenylephrine (2.5 ug to 40 ug bolus, via femoral vein) regularly induced elevations in arterial blood pressure with associated reflex bradycardia. Similarly graded doses of nitroglycerine induced a marked decline in arterial blood pressure, without expected tachycardia. As hypotension became more severe (during hemorrhage), atrioventricular conduction slowed and A-V block developed, resulting in statistically greater slowing in ventricular than in atrial excitation and contractile cycles. Heart failure during hemorrhage in the rat is characterized sequentially by severe bradycardia, depressed atrial contractile force, impaired conduction and A-V block, terminating in ventricular, atrial, and finally, in pacemaker failure. Baroreceptor reflexes were blunted or even absent in both young and old animals during induced hypotension. PMID- 1419869 TI - Heart rate reactivity in attention deficit disorder subgroups. AB - Beat-to-beat heart rate (HR) was analyzed for 9 contiguous seconds in a warned reaction time (RT) paradigm. Imperative stimuli were tones of three intensity levels (55, 78, and 100 db); a visual warning signal occurred 5 sec before tone onset. Baseline and reward conditions were run. Normal controls were contrasted with three Attention Deficit Disorder (ADD) subgroups: ADD-only, ADD with hyperactivity (ADDH), ADD with hyperactivity and aggression (ADDHA). The ADD subgroups were predicted to show less deceleration in HR because of their problem sustaining readiness to respond. Significant sex x group differences in HR levels and change scores were found. Overall, girls had higher HR levels than boys and the ADD-only group (boys and girls) had lower HRs than the other ADD groups. But, the ADD-only boys had more marked deceleration to the warning signal and acceleration to the tones than the other ADD boys, whereas the ADD-only girls were no more reactive than the ADDH and ADDHA girls. Control girls had the highest HR levels and were the most reactive to stimuli. Control boys and ADD only boys had similar HR levels and reaction patterns. ADD-only girls appear to be underaroused, whereas ADD-only boys do not. Results suggest that cardiac measures can provide external validation of disruptive and nondisruptive ADD subtypes. PMID- 1419870 TI - Predictors of myocardial infarction over a span of 30 years in Roseto, Pennsylvania. AB - Predictors of myocardial infarction with or without survival were sought in a 30 year study of Roseto, Pennsylvania, a nearly exclusively Italian community of approximately 1,600, compared to the immediately adjacent town of Bangor with a population of approximately 5,000. At the start of the study the death rate from myocardial infarction among men in Roseto was less than half that in Bangor despite an equal prevalence of the usual risk factors, mainly smoking and diet. The communities were followed prospectively for 30 years during a striking social change in Roseto toward less family and community cohesion and more commitment to individual goals and adherence to materialistic values. During this period the prevalence of and mortality from myocardial infarction increased sharply to equal the situation in Bangor. The predictive values of measurements made of Rosetans during individual examinations in 1962-63 were tested against the outcome in 1990. Those who experienced fatal myocardial infarction and those who had a well documented infarction and survived were matched with and compared to controls. Although subjects with cholesterol concentration above 200 were twice as likely to experience myocardial infarction as those with concentrations below 200, less than 20% of those whose cholesterol concentration was above 200 experienced any evidence of myocardial infarction over the nearly 30-year period. Moreover, there were no significant differences between the coronary patients, with or without survival, and their sex, age, and cholesterol matched controls; nor were smoking, evidence of hypertension, diabetes, or obesity predictive of significant differences between the two groups. These data lead to the inference that while those with the conventional risk factors are more likely to develop myocardial infarction than are those without the risk factors, an even larger proportion of the population may have the risk factors and not succumb to myocardial infarction over a period of nearly three decades. PMID- 1419868 TI - The putative role of free radicals in the loss of neuronal functioning in senescence. AB - One of the hallmarks of the aging process is a loss of sensitivity in central neuronal receptors to agonist stimulation. This appears to be especially true in central (hippocampal, striatal) muscarinic cholinergic systems and in the striatal dopamine systems. For these two systems, any decline in their sensitivity can be of extreme importance in determining the behavioral capabilities of the organism. Decrements in the striatal dopamine system may be reflected as motor behavioral deficits, while the central cholinergic systems play a major role in the processing of memory through the activation of muscarinic receptors (mAChR). Declines in the function of these receptors appear to be at least partially responsible for the marked deterioration of cognitive function in normal aging and, more notably, in Alzheimer's disease (AD). Previous work has indicated only minimal success in improving performance in tasks that assess memory in senescent animals or humans with pharmacological agents which enhance cholinergic functioning. The present review describes research that indicates that two of the factors involved in this decline in receptor sensitivity include: (a) decreased receptor concentrations and (b) age-related decrements in signal transduction pathways. Studies are reviewed that indicate that the oxidative neural damage that occurs via kainic acid or ionizing radiation parallel those seen in aging. It is suggested that the common mechanism that may exist among all of the age-, disease-, excitatory amino acid- or radiation-induced deficits in neuronal transmission may involve free-radical mediated alterations in membrane integrity through lipid peroxidation. PMID- 1419871 TI - Ivan Pavlov on communist dogmatism and the autonomy of science in the Soviet Union in the early 1920s. 1923. AB - On 25 September, 1923, two days before his 74th birthday, Ivan Petrovich Pavlov stood before a class of medical students assembled in the auditorium of his Alma Mater, the Military Medical Academy in Leningrad. Pavlov, the recipient of the Nobel prize in medicine in 1904 for his work in physiology, was about to address his first class of the new academic year, and, as was his custom, he had prepared his first lecture on a general theme. This was an especially significant address, however, for in it Pavlov reviewed the impressions he had gathered during his travels in Western Europe and the United States in the summer of 1923, and he criticised the prevailing ideology of Soviet communism by attacking the ideas of Nikolai Ivanovich Bukharin, then the leading expositor of Bolshevik Marxism. An English translation of the lecture is printed below. PMID- 1419872 TI - Detection of alpha S1-casein in vomit from bottle-fed babies by enzyme-linked immunosorbent assay. AB - This study describes a sensitive enzyme-linked immunosorbent assay (ELISA) using rabbit anti-bovine alpha S1-casein antibody for the detection of commercial milk and milk-containing vomit. The antibody does not react with other human body fluids such as breast milk. The stability of alpha S1-casein antigenic activity was examined after storage at different temperatures and enzyme digestion. There was no decrease after storage for one year at room temperature but 40% of the activity was lost after 6 months at 37 degrees C. Enzyme digestion (6 hours, 37 degrees C) resulted in 65 approximately 70% loss of activity but the antibody reacted with the peptide fragments of alpha S1-casein. Vomit samples from 3 normal infants were tested by ELISA, and alpha S1-casein could be detected in 1 cm2 stain. PMID- 1419873 TI - Fatal poisonings in Jutland (Denmark) during the 1980s. AB - During the period 1980 through 1989 a total of 1029 cases of fatal poisoning (638 men and 391 women) were examined at the Department of Forensic Medicine, Aarhus University, Denmark. In 68% of the cases death had been caused by drugs, whereas acute alcohol poisoning and carbon monoxide accounted for 15% and 14% of the cases, respectively. Alcohol was detected in more than half of the 1029 fatal poisoning cases, and in 42% of all cases the blood alcohol concentration was above 0.8 g/kg. In 57% of the cases death was categorized as accidental, only in 31% of the cases as suicide. Accidental deaths were especially predominant amongst drug and/or alcohol abusers. Propoxyphene was the drug found to have caused most fatal poisonings during the decade (30% of the drug-related deaths). Most of the propoxyphene-related deaths occurred during the early and mid eighties. Barbiturate poisonings were quite frequent during the first half of the eighties. However, the number of deaths caused by barbiturates decreased significantly after 1986, when most barbiturates were withdrawn from the market. The number of deaths caused by narcotics and analgesics increased during the survey period, while no specific tendency was observed concerning antidepressants. PMID- 1419874 TI - Application of DNA techniques for identification using human dental pulp as a source of DNA. AB - Dental pulp tissue could be obtained in most cases from materials obtained under experimental conditions and from forensic casework (air accidents, burned and putrefied bodies). Teeth extracted during dental treatment (n = 30) were stored for 6 weeks and 4 years at room temperature. In addition teeth (n = 10) extracted from jaw fragments that had been stored for 15 years at room temperature, and teeth extracted post mortem from actual identification cases (n = 8) were investigated. Following extraction from dental pulp tissue the DNA concentration was measured by fluorometry. The amount of DNA obtained from the dental pulp tissue of a single tooth varied from 6 micrograms to 50 micrograms DNA. In most cases high molecular weight DNA was still present although the major portion consisted of degraded DNA. Genomic dot blot hybridization for sex determination using the biotinylated repetitive DNA probe pHY 2.1 was performed and sex was correctly classified in all cases using 50-100 ng target DNA. PCR typing of the HLA-DQ alpha and ApoB 3' VNTR systems from dental pulp tissue DNA was in agreement with the results obtained from blood, bloodstains, or lung tissue. In addition, Southern blot analysis of selected samples using the single locus VNTR probe pYNH24 was successfully performed. In all cases the DNA recovered from dental pulp was unsuitable for multilocus probe analysis. PMID- 1419875 TI - Measurement of digitalis-glycoside levels in ocular tissues: a way to improve postmortem diagnosis of lethal digitalis-glycoside poisoning? I. Digoxin. AB - Prompted by animal studies reporting the accumulation of digitalis-glycosides in ocular tissues, we investigated whether measurement of digoxin levels in human ocular tissues can improve the postmortem diagnosis of lethal digoxin intoxication. Digoxin was measured in the vitreous humor and choroid-retina of patients who had received in-patient treatment with digoxin prior to death (therapeutic group) and in a single case of suicidal intoxication. The results were compared with the digoxin levels in the femoral vein blood, myocardium, kidney and liver, and evaluated in light of the medical history of each patient. In the therapeutic group the mean digoxin level was higher in the choroid-retina than in other tissues and body fluids. The range of variation in levels in the choroid-retina following therapeutic doses was comparable to that in the other tissues. An extremely high level of digoxin was present in the choroid-retina in the case of suicidal intoxication. In all cases, levels in the vitreous humor were very low compared to those in the choroid-retina. Hence, it is unlikely that significant distortion of choroid-retinal levels occurs due to postmortem diffusion of digoxin into the vitreous body. Our results indicate that measurement of digoxin levels in the choroid-retina can aid the postmortem diagnosis of lethal digoxin intoxication. PMID- 1419877 TI - Frequency of HLA DQA1 alleles in an Italian population. AB - A sample of 103 Italians was tested for HLA-DQA1 polymorphism using the polymerase chain reaction (PCR) and dot blot hybridization. Results were in Hardy Weinberg equilibrium. The power of discrimination was 0.91 and the rate of exclusion 56.7. The frequencies of the DQA1*0201 and DQA1*0301 alleles were found to be significantly different from other Caucasian populations. PMID- 1419876 TI - Measurement of digitalis-glycoside levels in ocular tissues: a way to improve postmortem diagnosis of lethal digitalis-glycoside poisoning? II. Digitoxin. AB - Postmortem digitoxin levels in the choroid-retina and vitreous humor of patients who had undergone digitoxin therapy (therapeutic group) and in one case of suicidal digitoxin poisoning were measured and compared with levels in femoral vein blood, myocardium, kidney and liver. The results were interpreted in light of the medical history of each patient. The digitoxin level in the choroid-retina of the single case of suicidal poisoning was far higher than the choroid-retinal levels in the therapeutic group. In the latter, variation in choroid-retinal levels was comparable to that in the other tissues. In cases where the choroid retina of the right and left eyes were examined, digitoxin levels in both eyes were essentially equal. There was no indication of significant changes in choroid retinal levels due to postmortem diffusion of digitoxin into the vitreous body. Based on these results, determination of digitoxin levels in the choroid-retina could contribute to improving postmortem diagnosis of lethal digitoxin poisoning. PMID- 1419878 TI - Time-dependent pericellular expression of collagen type IV, laminin, and heparan sulfate proteoglycan in myofibroblasts. AB - Human skin wounds (n = 62) with a wound age between 5 h and 6 weeks were investigated. The appearance of cell-associated pericellular basement membrane components collagen type IV, laminin and heparan sulfate proteoglycan (HSPG) in myofibroblasts was evaluated by immunohistochemistry. Laminin and HSPG were first detectable around myofibroblasts approximately 1.5 days after wounding. Collagen type IV did not appear before the 4th day after wound infliction. In wounds more than 7 days old, 94% of the cases showed fibroblastic cells positively staining for laminin, 70% of the wounds contained fibroblastic cells positive for HSPG and in 63% a positive reaction for collagen type IV was obtained around these cells. The numbers of the cases as well as of the cells positively stained for laminin exceeded the corresponding values for HSPG and especially for collagen type IV. The pericellular appearance of laminin or HSPG around myofibroblasts, therefore, indicates a wound age of at least approximately 1.5 days. The pericellular localization of collagen type IV indicates a survival time of approximately 4 days or more. Since these proteins are still detectable in the pericellular region of myofibroblasts in skin wounds with advanced wound age (6 weeks) further information for the time-estimation of older human skin lesions cannot be obtained. A semiquantitative analysis revealed no significant correlation between the number of positively stained cells and the wound age, rendering this parameter unsuitable for a practicable time-estimation of human wounds. PMID- 1419879 TI - A unique case of naturally occurring mummification of human brain tissue. AB - When skulls and bones were exhumed from a mass grave in Bulgaria and subjected to medicolegal examination they were found to originate from 39 humans aged 36-60 years old who had been buried approximately 45-50 years ago. Solid structures which strongly resembled shrunken human brain tissue were found inside 2 intact skulls. Among other bones 5 similar structures were found one of which was an almost entirely preserved human brain, and the others were fragments from different regions of the human brain. Samples of these structures were immersed in 15% aqueous glycerol solution to soften and were examined by light and electron microscopy. Samples of this material and of fresh human brain were subjected to elementary atomic spectral analysis. These complex studies indicated the samples to be naturally mummified human brain tissue and that this process had occurred due to specific conditions within the cranial cavities after burial. PMID- 1419880 TI - Lactate dehydrogenase isoenzyme patterns in vaginal injury of a 4-year-old girl. AB - Lactate dehydrogenase isoenzyme patterns indicative of vaginal injury were identified in extracts of a bloodstain on a pair of knickers belonging to a 4 year-old girl. No evidence of semen or saliva was detected in the stain. The result corroborated the clinical findings and provided strong evidence of child sexual abuse. PMID- 1419881 TI - A common origin for dental porcelain derived from an accused's hand and the decreased victim of an assault. AB - A small, solid fragment removed from a wound on a hand of a murder suspect was submitted to electron microprobe analysis and found to have the properties of dental porcelain. A sample of porcelain removed from the dental bridge of the deceased had an essentially similar elemental profile. This investigation assisted the Court by providing valuable objective evidence of a physical contact between the accused and the victim. PMID- 1419882 TI - Optimized amplification of the polymorphic system COL2A1. AB - The influence of various amplification parameters on the demonstration of COL2A1 patterns was examined in serial experiments. The combination of 6 optimized parameters (concentration of primers, nucleotides, Taq polymerase, K+, Mg2+, number of cycles) led to an approximately tenfold increase in sensitivity and a decrease in allelic drop-out. In unequal mixtures of DNA from 2 individuals the weakest component was detectable in dilutions down to 1:20. In a small population sample (n = 120) 10 alleles could be demonstrated. PMID- 1419884 TI - Estrogen receptor and C19-5-ene-steroid concentrations in the nuclear fraction from human breast carcinoma tissue. AB - The adrenal-derived estrogen 5-androstene-3 beta,17 beta-diol (ADIOL) is estrogenic at the concentrations found in the blood of Western women. We have now measured the concentrations of both ADIOL and the estrogen receptor (ER) in the nuclear fraction (800 g pellet) of 89 primary human mammary tumors. No difference was found in nuclear ADIOL concentrations in tumors from 45 pre- and 44 postmenopausal women. Significantly higher nuclear ADIOL concentrations were found in 49 ER negative tumors compared to 40 ER positive tumors (P < 0.005). A similar relationship applied in the postmenopausal group (P = 0.01) and the premenopausal group, but in this latter instance failed to reach significance (P = 0.1). In ER positive tumors there was no correlation between ADIOL and ER nuclear levels. ADIOL was present in the total particulate fraction (100,000 g pellet) at twice the concentration found in the nuclear 800 g pellet and again no difference was found in its concentration in tumors from 20 pre- compared to 34 postmenopausal women. Dehydroepiandrosterone was also measured in the 800 g fraction of 45 tumors and its concentration, which was some 10-fold higher than ADIOL and significantly correlated with that steroid, was again independent of menopausal status. The higher concentration of C19-5-ene-steroids in ER negative cellular fractions could be due to differences in their metabolism; ER negative tumors either lack, or possess very low levels of, hydroxysteroid sulfotransferase which catalyzes formation of sulfate esters of C19-5-ene steroids previously observed to be major metabolites produced by ER positive cells. Higher concentrations of free steroids in ER negative cells would then be available for combination with membranes and non-specific binding sites throughout the cell. PMID- 1419883 TI - Hormone stimulated steroid biosynthesis in granulosa cells studied with a fluorogenic probe for cytochrome P-450SCC. AB - The regulation of steroidogenesis by luteinizing hormone (LH) was studied in granulosa cells during follicular development using a fluorescent reporter assay based on the metabolism of a fluorescent probe specific for cytochrome P-450SCC (cholesterol side-chain cleavage enzyme). Intact granulosa cells or mitochondria were obtained from the first (F1) second (F2) and third (F3) largest preovulatory follicles of the hen ovary and incubated with the fluorogenic substrate. Metabolism of this substrate by cytochrome P-450SCC generates the highly fluorescent resorufin anion (the fluorescent reporter). In both mitochondria and intact granulosa cells, incubated with the fluorescent substrate, an increase in resorufin fluorescence was observed and the increase was greater in samples derived from F1 than in samples from F2 or F3. In cells, LH added simultaneously with the P-450SCC substrate significantly increased resorufin fluorescence above control values in a time- and dose-dependent manner up to 2-3 h after the incubation was initiated. Forskolin and 8-bromo-cAMP also stimulated metabolism of the P-450SCC substrate significantly by 15 min. When granulosa cells were preincubated with LH before exposure to the P-450SCC substrate resorufin fluorescence was significantly attenuated compared to controls (not exposed to LH in the preincubation period). The decrease in resorufin fluorescence observed when cells were pretreated with LH, may be due to the release of cholesterol from endogenous pools and its competition with the exogenous fluorogenic for the substrate P-450SCC enzyme. In granulosa cells that were preloaded with the P 450SCC substrate, the stimulatory effect of LH treatment remained constant from 30 min to 2 h after hormone addition. The results show that this fluorescent probe can be used in a rapid assay for the continuous measurement of the acute effects of hormone agonists on cholesterol conversion to pregnenolone in steroidogenic cells. PMID- 1419885 TI - Interaction of DP-TAT-59, an active metabolite of new triphenylethylene derivative (TAT-59), with estrogen receptors. AB - DP-TAT-59, (Z)-2-(4-(1-(4-hydroxyphenyl)-2-(4-isopropylphenyl)-1-butenyl) phenoxy)-N, N-dimethylethylamine, has been reported to inhibit estrogen stimulated growth of MCF-7 cells as well as rat uterus at lower concentrations than the hydroxymetabolite of tamoxifen (4-OH-TAM). In the present study, the growth of mouse Leydig cell tumor, B-1F cells were also more effectively inhibited by DP-TAT-59 than 4-OH-TAM. Additionally, the expression of estrogen responsive element ligated CAT gene transfected into B-1F cells was also suppressed by DP-TAT-59. Thus, the interaction of DP-TAT-59 with estrogen receptor (ER) was characterized and compared with that of 4-OH-TAM using immature rat and bovine uteri. The dissociation constant of DP-TAT-59 to ER of immature rat uterus was 0.24 nM and was similar to that of 4-OH-TAM (Kd = 0.20 nM) and estradiol (Kd = 0.29 nM). Using sucrose density gradients, the sedimentation constant of DP-TAT-59 with bovine uterus was 4.9S, which was similar to that of estradiol (5.1S) and 4-OH-TAM (5.3S). However, the elution profile of the DP-TAT 59-ER complex from a DEAE-Sephadex column was different for both estradiol-and 4 OH-TAM-ER complexes. These results suggest that ER forms different complexes with DP-TAT-59 than estradiol or 4-OH-TAM, while the ER binding affinity of these compounds are similar to each other. PMID- 1419886 TI - Immunochemical specificity of placental NADPH cytochrome c (P-450) reductase in neoplastic and non-neoplastic human tissue. AB - NADPH cytochrome c (P-450) reductase was purified from human placental microsomes using a combination of affinity and gel filtration chromatography. Affinity chromatography using agarose-hexane-adenosine 2'5 diphosphate resulted in two protein bands being detected by SDS-PAGE of approximate MwS 68 and 75 kDa. Fractions containing the two proteins were pooled, and then resolved using Sephacryl S-200. Both of the purified proteins displayed enzyme activity, measured by their ability to reduce cytochrome c. The 75 kDa protein obtained was used to immunize three female New Zealand white rabbits. The IgG fraction was partly purified from rabbit sera which suppressed placental microsomal NADPH cytochrome c reductase activity by > 80% using 33% ammonium sulphate. The procured antibody suppressed androstenedione aromatase activity in microsomal preparations of human placental and breast adipose tissue, and NADPH cytochrome c reductase activity in prostate (benign and malignant), MDA-MB-231 breast cancer cells, breast adipose, Hep G2 hepatoma cells and placental microsomal preparations. The extent of NADPH cytochrome c reductase inhibition varied in the order of malignant prostate < benign prostate < MDA < breast adipose < Hep G2 < placenta. The results suggest that human placental NADPH cytochrome c (P-450) reductase shares common antigenic epitopes pertinent to its capability of reducing cytochrome c in all of the above-mentioned tissues. In attempting to associate possible changes in NADPH cytochrome c reductase activity imposed by neoplasia to the obtained immunochemical cross reactivity and enzyme activity results, it was noted that microsomes obtained from MDA cells exhibited enzyme activity significantly less than that of breast adipose microsomes (1.6 and 8.1 nmol/min/mg protein, respectively) and by comparison showed 6% less homology towards the placental antibody. The results obtained for benign and malignant prostate showed no significant difference between the neoplastic states as adjudged by enzyme activity and immunochemical assays. PMID- 1419887 TI - Biotin-hydrazide derivatives for the development of steroid enzyme-linked immunoassays. AB - We are describing the synthesis and use of biotinamidocaproyl-derivatives of 18 oxocortisol-3-carboxymethoxylamine for the development of enzyme labels using the avidin-peroxidase system for the design of enzyme-linked immunoassays (ELISA). An ELISA for 18-oxocortisol and -hydroxycorticosterone was devised which showed improved sensitivity and specificity in comparison to an RIA using a tritiated tracer. The system is easy to prepare and offers the possibility to design immunoassays when no tritiated tracer is available. PMID- 1419888 TI - The interrelationships between nonapeptide and steroid hormones secretion by bovine granulosa cells in vitro. AB - The effects of adding oxytocin (OT) and arginine-vasopressin (AVP) on progesterone and estradiol-17 beta secretion by bovine granulosa cells in culture were studied. The influence of these steroids on OT and AVP release was also evaluated. OT (1, 10, 100 or 1000 mIU/ml) stimulates both progesterone and estradiol output. Small doses (10 pM/ml) of exogenous progesterone or estradiol stimulated a surge in OT, while the intermediate doses (100 or 1000 pM/ml) had no influence, and large doses (10,000 pM/ml) inhibited OT secretion by granulosa cells. Thus, a potential regulatory loop between OT and steroid hormone release by granulosa cells was demonstrated. Stimulation of a surge in steroids by OT, activation of OT release by small doses of steroids and inhibition of OT secretion by excess steroids may suggest the existence of a feedback mechanism regulating these hormones production. Addition of AVP (1, 10, 100 or 1000 pM/ml) inhibited progesterone and stimulated a surge in estradiol, while steroid hormones did not induce AVP release. These data suggest the regulation of ovarian steroidogenesis by AVP, feedback influences are less likely. PMID- 1419889 TI - Bioconversion of steroids by Cochliobolus lunatus--II. 11 beta-hydroxylation of 17 alpha, 21-dihydroxypregna-1,4-diene-3,20-dione 17-acetate in dependence of the inducer structure. AB - The 11 beta-hydroxylase of the filamentous fungus Cochliobolus lunatus m 118 was induced with the substrate 17 alpha, 21-dihydroxypregna-1,4-diene-3,20-dione 17 acetate (11 beta-deoxyprednisolone 17-acetate) itself, substrate analogues, different pregnane compounds, sterols, intermediates of microbial sterol side chain degradation or bile acids, together with 24 different steroids in a standardized test system. The resulting 11 beta-hydroxylation rate, leading to prednisolone 17-acetate and prednisolone, respectively, was determined and compared with the hydroxylation rate of non-induced cultures. The transformation yield strongly depended on the inducer structure. The microbial sterol side-chain degradation intermediates (20S)-20-hydroxymethylpregn-4-en-3-one and the corresponding pregna-1,4-diene compound caused the highest induction effects (induction factors 5.1 and 4.9, respectively). The metabolism of (20S)-20 hydroxymethylpregna-1,4-dien-3-one during the cultivation was elucidated. The induction effect decreased with the rising oxidation of the inducer. The significant increase of the 11 beta-hydroxylation rate of 1-dehydro-pregnane substrates by specific induction allows alternative pathways to glucocorticoid partial syntheses. PMID- 1419890 TI - GC-MS studies of 16-androstenes and other C19 steroids in human semen. AB - Human semen was examined for the presence of 16-androstenols, 16-androstenones and androgens. Extracts were analysed by gas chromatography-mass spectrometry after derivatization of steroids under study. In a qualitative study, 5 alpha androst-16-en-3 alpha- and 3 beta-ols, 5,16-androstadien-3 beta-ol and 5 alpha androstan-3 beta-ol were detected in a semen pool A. Hydroxyl groups were converted to tert-butyldimethylsilyl ethers, the ions selected for monitoring being [M-57]+, consistent with loss of the tert-butyl group. For a more detailed quantitative study, a second semen pool B was used. In this case, all hydroxyl groups were converted to trimethylsilyl ethers, while oxo groups were not derivatized. As with semen pool A, separation of steroids was achieved using capillary gas chromatography with appropriate temperature programming. Quantification was carried out by mass spectrometry using selected ion monitoring of two significant ions and appropriate internal standards. The following steroids were identified at the concentrations indicated: 5 alpha-androst-16-en-3 alpha- and 3 beta-ols and 5,16-androstadien-3 beta-ol (concentration range, 0.5 0.7 ng/ml). 5 alpha-Androst-16-en-3-one and 4,16-androstadien-3-one were also present at levels of 0.7-0.9 ng/ml. Two androgens, testosterone and 5 alpha dihydrotestosterone were found at concentrations of 0.5 and 0.3 ng/ml, respectively. These data, showing the presence of 16-androstenes and androgens in human semen, appear to be consistent with testicular formation of these steroids. The possible significance of the odorous 16-androstenes is discussed. PMID- 1419892 TI - Regulation by dexamethasone of the 3 beta-hydroxysteroid dehydrogenase activity in adult rat Leydig cells. AB - The effect of long-term in vitro treatment with dexamethasone, insulin and/or LH on the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity and the testosterone level was examined in cultures of Leydig cells from adult rats. A rapid and simple method for measuring the 3 beta-HSD activity has been developed, in which the NADH, generated by 3 beta-HSD, reduced nitroblue tetrazolium to a product with absorption maximum at 560 nm. Km for the reaction was 8.1 microM and Vmax was 12.7 nmol/min x mg protein. Addition of 0.1 or 1 microM dexamethasone for 44 h decreased the 3 beta-HSD activity to 83% and the basal testosterone level to 64% of control value after 22 and 44 h of culture. Addition of 1 nM insulin inhibited the 3 beta-HSD activity to 90% after 44 h of culture, whereas the testosterone level was increased after 3 h. Addition of 0.1 ng/ml LH did not affect the 3 beta-HSD activity in Leydig cells from adult rats. Concomitant treatment of the cells with dexamethasone and insulin inhibited the 3 beta-HSD activity to 74%, indicating an additive effect, whereas no additive effect on the testosterone level was observed. The results demonstrate that the 3 beta-HSD activity can be measured in a rapid and reliable way by measuring the reduction of nitroblue tetrazolium. Furthermore, the results suggest that dexamethasone acts on 3 beta-HSD through a mechanism different from that of insulin, as an additive effect was observed. PMID- 1419891 TI - Soy of dietary source plays a preventive role against the pathogenesis of prostatitis in rats. AB - This study examined the effects of diet on the development of prostatitis in male rats. Adult male rats were placed on either of two specially formulated diets which differed from one another by the presence or absence of soy as the protein source. A third group of rats (control) was fed standard laboratory rat chow which also includes soy as a source of protein. After 11 weeks, it was found that rats maintained on soy-free diet developed prostatitis mainly in the lateral lobe of the prostate. Increased severity and incidence of prostatitis in rats maintained on the soy-free diet coincided with a significant decrease in urinary excretion of various phytoestrogens. There was no evidence of prostatitis in rats maintained on soy-containing diets. Urinary excretion of phytoestrogens in rats maintained on soy-containing diet was also not different from controls. These results suggest that soy as a dietary source plays a protective role against the development of prostatitis in rats, and indicate that the ventral, lateral and dorsal lobes of the rat prostate have different sensitivities to alterations in dietary factors. PMID- 1419893 TI - Determination of urinary cortisol with three commercial immunoassays. AB - Urinary cortisol determination was performed with three commercially available immunoassays: one enzyme-immunoassay (Cortisol Biotrol) (EIA) and two radioimmunoassays: Quanticoat Cortisol (Kallestad Diagnostics) (KD-RIA) and GammaCoat Cortisol (Clinical Assays) (CA-RIA). Four procedures were carried out. Procedure I (methylene chloride extraction) was applied to EIA and CA-RIA and procedure II (ethyl acetate extraction) to KD-RIA. Procedure III combining procedure I and column chromatography on Sephadex LH 20 in methylene chloride was applied to the three kits. Procedure IV consisting of carbon tetrachloride preextraction and extraction with cyclohexane-ethyl acetate (50:50, v/v) was applied to CA-RIA. The results obtained were compared with those of the reference technique, "on-line" HPLC with u.v. detection. Two groups of results were arbitrarily considered, those below (n = 28) and those above (n = 6) 270 nmol/l. In the first group, the results were markedly overestimated when the procedure was limited to solvent extraction. Conversely, the third procedure proved the efficiency of the chromatographic step since specificity was greatly improved in the three cases, the levels obtained with either kits being similar to those of the reference technique. The second group of results (above 270 nmol/l) yielded by the three kits were not always higher than those of HPLC when the procedure was limited to solvent extraction. When column chromatography was included in the procedure, the results were comparable to those of HPLC in three cases and lower in the three others. Since, the latter samples were collected after cortisol administration, and overestimated cortisol values obtained by HPLC might be due to the interference of some cortisol metabolites. PMID- 1419894 TI - Effect of serum and serum lipoproteins on testosterone production by adult rat Leydig cells in vitro. AB - The effect of serum factors other than luteinizing hormone on Leydig cell testosterone secretion was examined using an in vitro bioassay system based on the stimulation of purified adult rat Leydig cells during a 20 h incubation in the presence of a maximal dose of human chorionic gonadotrophin (hCG). Charcoal extracted serum and testicular interstitial fluid (IF) from normal adult male rats were separated into lipoprotein and lipoprotein-deficient fractions by density ultracentrifugation. Stimulatory bioactivity was found in the lipoprotein fraction of both serum and IF, although the levels of lipoprotein and corresponding bioactivity recovered from IF were significantly lower (25%) than those of serum. There was no difference between the effects of serum lipoproteins on Leydig cell testosterone production stimulated by either hCG or dibutyryl cAMP. In time-course studies, the serum lipoprotein fraction had no effect on hCG stimulated testosterone production in vitro at 3.0 or 6.0 h, but partially prevented the normal decline in hCG-stimulated testosterone production after 6.0 h. In contrast, unfractionated serum was stimulatory at all time-points. In the absence of hCG, the lipoprotein fraction was stimulatory at both 6.0 and 20 h, although not at 3.0 h. The lipoprotein-deficient protein fraction of serum had no effect on hCG-stimulated testosterone production alone, but significantly enhanced the bioactivity of the lipoprotein fraction, and caused a dose-dependent stimulation of testosterone production in the presence of a constant concentration of serum lipoproteins. Both a stimulatory peak of activity (apparent MW 40-80 kDa), and a large MW (> 100 kDa) inhibitor of testosterone production were identified in serum after fractionation by gel filtration (Sephadex G-100). The data indicate that (i) the stimulatory effect of serum on short-term hCG-stimulated Leydig cell testosterone production in vitro is predominantly due to the serum lipoprotein fraction, possibly by providing additional precursors for testosterone synthesis, (ii) the biological activity of the lipoproteins is influenced by both stimulatory and inhibitory serum proteins in addition to luteinizing hormone, and (iii) that serum lipoproteins may be involved in supporting Leydig cell steroidogenesis in vivo. PMID- 1419895 TI - Participation of a cytochrome P450 enzyme from the 2C subfamily in progesterone 21-hydroxylation in sheep liver. AB - Progesterone 21-hydroxylation in hepatic microsomes from adult male sheep is a quantitatively important metabolic pathway (0.27 +/- 0.08 nmol deoxycorticosterone formed/min/mg protein; representing 13-25% of total progesterone conversion). This study was undertaken to determine whether the ovine hepatic progesterone 21-hydroxylase may be another member of the P450 2C subfamily, normally associated with progesterone 21-hydroxylation in rodent liver. An IgG preparation raised in rabbits against purified rat liver microsomal cytochrome P450 2C6 was found to recognize a single antigen (MW 52 kDa) in sheep liver microsomes. This protein was present in sheep liver (apparent concentration 16 +/- 4 ng/micrograms microsomal protein) representing approx. 28% of the corresponding content of P450 2C6 in untreated rat liver. Preincubation of the anti-P450 2C6 IgG with hepatic microsomes was found to decrease the rate of progesterone 21-hydroxylation to 50-80% of uninhibited control. Taken together, from these findings it is apparent that a P450 enzyme, most likely from the 2C subfamily, catalyses deoxycorticosterone formation from progesterone in sheep liver and that this is a quantitatively important pathway of progesterone hydroxylation in these fractions. PMID- 1419897 TI - Differential regulation of transforming growth factor alpha autoinduction in a nontransformed and transformed epithelial cell. AB - Addition of transforming growth factor alpha (TGF-alpha) to cultured human keratinocytes results in enhanced expression of TGF-alpha mRNA. This phenomenon of TGF-alpha autoinduction is also observed in a TGF-alpha responsive colon cancer cell line, LIM 1215. In the present study, regulation of TGF-alpha autoinduction is examined in these two cell types. In human keratinocytes, but not in LIM 1215 cells, the increase in steady-state TGF-alpha mRNA following administration of TGF-alpha is due to stabilization of the 4.8-kilobase TGF-alpha transcript, as determined by actinomycin D decay curves. Nuclear run-on experiments confirmed transcriptional control in LIM 1215 cells. Basal and TGF alpha-stimulated TGF-alpha expression is mediated, at least in part, through a protein kinase C-dependent pathway in both cell types, as determined by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), which attenuates TGF-alpha mRNA accumulation. In the keratinocytes, but not in the LIM 1215 cells, basal TGF-alpha expression is mediated through an epidermal growth factor receptor-dependent pathway, as determined by antibody blockade of the epidermal growth factor receptor. Thus, differential regulation of TGF-alpha autoinduction exists in these nontransformed and transformed epithelial cell types. PMID- 1419896 TI - Protein product of a human intronless calmodulin-like gene shows tissue-specific expression and reduced abundance in transformed cells. AB - The recently identified NB-1 mRNA is transcribed from a single intronless gene, previously thought to be an unexpressed calmodulin pseudogene. Although expression levels of the three known human calmodulin genes fluctuate only slightly in all cell types and tissues examined, NB-1 expression is limited to certain cells of pseudostratified and stratified epithelial tissues. Like calmodulin, the protein encoded by NB-1 is heat stable and binds to phenyl Sepharose in a calcium-dependent manner. Despite the shared identity of 85% of their 148 amino acids, however, calmodulin and NB-1 protein are easily distinguished electrophoretically and immunologically. Polyclonal antibodies prepared against recombinant NB-1 protein recognize a protein with an apparent molecular weight of 16,000 which is abundant in cultured normal human mammary epithelial cells, but which is absent or barely detectable in fibroblasts or tumor cell lines. The immunohistochemical distribution of NB-1 protein in histologically normal tissues suggests that expression of the gene is regulated during epithelial differentiation. The majority of a small number of malignant tissues examined had lowered or undetectable NB-1 protein expression relative to normal tissues. Given its restricted distribution, the NB-1 protein may be involved in the initiation or maintenance of certain differentiated functions. Its absence may be due to or necessary for the manifestation of the transformed phenotype in certain cell types. PMID- 1419898 TI - Tissue-specific expression of two isoforms of chicken fibroblast growth factor receptor, bek and Cek3. AB - Chicken bek and Cek3 are isoforms of the fibroblast growth factor receptor which consist of primary structures that are identical except for a variation within the last of three immunoglobulin-like repeats in the ligand-binding domain. Northern blot analysis using isoform-specific probes revealed that the bek mRNA is expressed exclusively in lung, whereas the Cek3 mRNA is expressed prominently in brain and weakly in lung. We further localized these transcripts in brain and lung by in situ hybridization histochemistry. In lung, the expression of the bek and Cek3 transcripts was distinguished in the smooth muscle of the parabronchus and in the arterial adventitia. On the other hand, in brain, the Cek3 transcript was detected in three areas: the corpus medullare of the metencephalon (cerebellum), the archiastriatum of the telencephalon, and the ependymal cells of the ventriculare of the mesencephalon. Two putative exons corresponding to isoform-specific sequences, respectively, were found to be closely located on the chicken genome. These results indicate that bek/Cek3 isoforms are derived from the same premessenger and that their expression is regulated in a tissue- or even area-specific manner. Moreover, another potential isoform produced by a new splice site within the Cek3-specific exon has been isolated. PMID- 1419899 TI - Protein tyrosine phosphatase activation during nerve growth factor-induced neuronal differentiation of PC12 cells. AB - We have studied the role of protein tyrosine phosphatases (PTPases) during neuronal differentiation of PC12 cells. Nerve growth factor (NGF), a well characterized differentiating agent for these cells, led to a decrease in DNA synthesis within 24 h. This was accompanied by a 2- to 3-fold increase in the activity of PTPases, measured as the dephosphorylation of polyacidic or polybasic substrates phosphorylated on tyrosine. PTPase activation was independent of cell density and proportional to NGF concentration, with a half-maximal effect occurring at 0.35 nM. High-performance liquid chromatography size exclusion chromatography revealed that PTPases with molecular masses of 550, 300, and 60 kilodaltons were activated in response to NGF. Additional studies showed that the presence of NGF made PC12 cells refractory to the mitogenic effect of epidermal growth factor. Our data indicate that NGF-induced neuronal differentiation and growth arrest in PC12 cells are associated with activation of several PTPases. We speculate that PTPase activation in response to NGF may inhibit the mitogenic actions of other growth factors. PMID- 1419900 TI - Interferon-inducible gene expression in HL-60 cells: effects of the state of differentiation. AB - The promyelocytic leukemia line HL-60 can be terminally differentiated in vitro to either monocyte/macrophages or granulocytes. We used this cell line to test whether the state of differentiation of a cell changes its response to interferon (IFN). The characteristics of expression of several IFN-alpha- and IFN-gamma inducible genes in undifferentiated and differentiated HL-60 cells were examined. p67, an IFN-gamma-inducible protein, was induced similarly in three cell types, whereas another IFN-gamma-inducible protein, p56, was induced strongly only in undifferentiated cells. In contrast, two isozymes of 2,5(A)-synthetase were induced better in differentiated cells in response to either IFN. Several IFN alpha-inducible mRNAs, e.g., 561, 6-16, 1-8, and 2A, were induced much more strongly in granulocytes than in macrophages or in undifferentiated cells. Electrophoretic mobility shift assays using the IFN-stimulated response element of gene 561 and nuclear extracts of IFN-alpha-treated cells revealed the appearance of one complex and the disappearance of another one, concomitant with differentiation of the cells to granulocytes. These observations suggest that expression of IFN-inducible genes in HL-60 cells is regulated by trans-acting factors whose activity changes with the state of differentiation of the cells. Our study may have implications in the optimal clinical use of IFNs. Inducing cellular differentiation may augment the efficacy of IFNs as antitumor agents. PMID- 1419901 TI - Changes in p34cdc2 kinase activity and cyclin A during induced differentiation of murine erythroleukemia cells. AB - Hexamethylene bisacetamide (HMBA)-induced murine erythroleukemia (MELC) differentiation is characterized by a prolongation of the initial G1 which follows passage through S phase in the presence of inducer. Commitment to terminal cell division is first detected in a portion of the cell population during this prolonged G1. HMBA-induced commitment is stochastic. This study has examined changes in two known cell cycle regulators, p34cdc2 and cyclin A, in cycle-synchronized MELC in the absence and presence of HMBA. Histone H1 kinase activity of p34cdc2, and the levels of CDC2Mm mRNA, 1.8-kilobase mRNA of cyclin A, and cyclin A protein changed during cell cycle progression in MELC, and all of them were suppressed during G1. The suppression of the H1 kinase activity and cyclin A expression continued through the prolonged G1 in MELC cultured with HMBA, whereas p34cdc2 protein level did not vary through the cell cycle in MELC cultured without or with inducer. Phosphorylation of p34cdc2 in uninduced MELC gradually increased as cells progressed from G1 to S. In induced MELC, an increase in phosphorylation of p34cdc2 occurred during the prolonged G1, and prior to the exit of the bulk of the cells from G1 to S. These results suggest that in HMBA-induced MELC, p34cdc2 phosphorylation per se is not a limiting factor in determining G1 to S progression. The persistent suppression of cyclin A expression and histone H1 kinase activity may play a role in HMBA-induced commitment to terminal differentiation. PMID- 1419902 TI - Isolation and characterization of complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc. AB - The N-myc oncogene has been implicated in the pathogenesis of a number of human tumors, including childhood neuroblastoma and adult small cell lung cancer. We have isolated and characterized complementary DNA clones derived from a transcription unit, N-cym, located on the opposite DNA strand to N-myc, with extensive overlap existing between the 5' ends of the two transcription units. The N-cym gene, which can encode a 109-amino acid protein, is expressed during fetal development, as well as in tumor cell lines containing amplified N-myc loci, where it is expressed at very high levels. Although other examples of overlapping, opposite-strand eukaryotic genes exist, N-myc and N-cym are unique in that they appear to be coregulated in tumor cell lines under basal growth conditions and in response to the differentiating agent retinoic acid. This coregulation suggests that their protein products may be functionally interrelated during normal development and oncogenesis. PMID- 1419903 TI - Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. AB - The present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells. The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression. This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h. Similar effects were obtained for the c-fos gene. Run on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure. c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid-induced c-jun transcription. The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid-induced cells. In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts. Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism. Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419904 TI - Expression and phosphorylation of the retinoblastoma protein during induced differentiation of murine erythroleukemia cells. AB - Phosphorylation and dephosphorylation of the retinoblastoma protein, pRB, play a role in the control of cell cycle progression and expression of differentiation in eukaryotic cells. The regulation of pRB level and phosphorylation state was investigated during the induction of differentiation of murine erythroleukemia cells (MELC) by the chemical agent hexamethylene bisacetamide (HMBA). In MELC, there is a critical time in G1 or early S phase when HMBA must be present in order to induce differentiation. This is followed by prolongation of the subsequent G1 phase, resumption of progression through the cell cycle for several generations, and then cell cycle arrest in G1-G0. Associated with HMBA-induced prolongation of G1, there is an increase in the amount of the underphosphorylated form of pRB. A variant cell line (DS19/VCR-C) with accelerated kinetics of HMBA mediated differentiation shows a more marked increase in underphosphorylated pRB. In culture with HMBA, as MELC resume progression through the cell cycle, pRB is present in the phosphorylated form. The total amount of pRB increases approximately 3-fold over the succeeding cell divisions prior to terminal arrest in G1. This increase in pRB is inhibited by dexamethasone, which also blocks HMBA induced MELC differentiation. During this period, RB mRNA also increases approximately 3- to 5-fold, which reflects an increase in the rate of transcription, with no change in mRNA stability. The state of phosphorylation and amount of pRB appear to be involved in the control of HMBA-induced terminal cell division of MELC. PMID- 1419905 TI - Activation of NF-kappa B by interleukin 2 in human blood monocytes. AB - We report here that interleukin 2 (IL-2) acts on human blood monocytes by enhancing binding activity of the transcription factor NF-kappa B to its consensus sequence in the 5' regulatory enhancer region of the IL-2 receptor alpha chain (p55). Similarly, IL-2 activates NF-kappa B in the human monocytic cell line U 937, but not in resting human T-cells. This effect is detectable within 15 min and peaks 1 h after exposure to IL-2. Enhanced NF-kappa B binding activity is followed by functional activation in that inducibility of the IL-2 receptor alpha chain is mediated by enhanced NF-kappa B binding and that a heterologous promoter containing the NF-kappa B consensus sequence (-291 to -245) of the IL-2 receptor alpha chain gene is activated. In addition, IL-2 is capable of increasing transcript levels of the p50 gene coding for the p50 subunit of the NF-kappa B transcription factor, whereas mRNA levels of the p65 NF-kappa B gene remained unchanged. PMID- 1419906 TI - Stable induction of c-jun mRNA expression in normal human keratinocytes by agents that induce predifferentiation growth arrest. AB - A variety of agents can induce predifferentiation growth arrest (PGA) in human keratinocytes; these include transforming growth factor beta 1 (TGF-beta 1) and razoxane. We evaluated the ability of these and other agents to induce the expression of a variety of transcription factor genes including c-fos, c-myc, junB, and c-jun. The results show that both TGF-beta 1 and razoxane induce maximal c-jun mRNA expression 4 days after initiation of treatment concurrent with the development of PGA. In contrast, no detectable induction of c-fos, c myc, or junB was observed. Keratinocytes maintained in the presence of TGF-beta 1 for an additional 3 days continued to show high levels of c-jun mRNA, indicating stable induction. Razoxane treatment also induces PGA and high c-jun mRNA levels for 4 days, but thereafter a decay of c-jun expression occurs. Run-off transcription experiments comparing rapidly growing cells with cells treated with TGF-beta 1 for 4 days demonstrated a significant increase in transcriptional activity of the c-jun gene. This result indicates that the increase in c-jun gene expression is due in part to a change in transcriptional regulation of c-jun. The stable induction of c-jun mRNA in keratinocytes at the PGA state is unique because the induction of this gene is usually transient. The finding that c-fos is not coinduced suggests that c-Jun homodimers or other AP-1 heterodimers may be formed at the PGA state to facilitate the stable induction of c-jun mRNA. This experimental system should therefore serve as a model system to study the molecular mechanisms for the stable control of c-jun gene expression and the control of AP-1-dependent gene expression during the process of keratinocyte differentiation. PMID- 1419907 TI - Identification of an immediate early gene, pghs-B, whose protein product has prostaglandin synthase/cyclooxygenase activity. AB - We have characterized a growth factor-inducible gene, pghs-B, isolated by differential screening of a lambda complementary DNA library from RNA of serum stimulated NIH 3T3 cells which encodes a 604-amino acid protein presenting high similarity with prostaglandin G/H synthase (PGHS). Induction of both pghs-B mRNA and protein is rapid and remains at high levels for several hours. The increase in pghs-B mRNA is mainly due to transcriptional activation of the gene. PGHS-B has been expressed in the baculovirus system and has been demonstrated to be involved in prostaglandin synthesis and to be inhibited by indomethacin, demonstrating that PGHS-B is indeed an enzyme related to PGHS. The pghs-B gene maps to the [1G-1H2] region of the murine genome. PMID- 1419908 TI - Protein prenylation: key to ras function and cancer intervention? PMID- 1419909 TI - Functional analyses of albumin expression in a series of hepatocyte cell lines and in primary hepatocytes. AB - A series of simian virus 40-immortalized hepatocyte cell lines which are heterogeneous with regard to expression of albumin protein and RNA were characterized for their ability to transcribe the albumin gene. Nascent chain extension assay showed that albumin RNA levels in these cells were determined predominantly at the transcription level. The albumin promoter and enhancer sequences were fused to the bacterial chloramphenicol acetyltransferase gene; the ability of the resulting expression constructs to drive chloramphenicol acetyltransferase expression after transfection into these hepatocyte cell lines was measured. The activity of the albumin promoter and enhancer constructs in primary hepatocytes was also measured. The albumin promoter was expressed differentially in these cells; however, no correlation was found between the transcriptional efficiency of the transfected albumin promoter and endogenous albumin transcription. The albumin enhancer was functional in some but not all albumin-positive cells. The minimal albumin enhancer was mapped to a 330-base pair fragment extending from -9.94 kilobases (kb) to -10.27 kb; three elements within this fragment recently shown to be necessary for enhancer function in a murine hepatocyte cell line were also essential for albumin enhancer function in the rat hepatocyte cell line CWSV1. A transcriptional silencer was identified which could suppress the expression of the homologous albumin promoter and the heterologous herpes simplex virus thymidine kinase promoter. Preliminary analysis localized the albumin silencer between -11 and -12 kb. Our results suggest that multiple regulatory sequences may act cooperatively to determine efficient tissue specific expression of the albumin gene. PMID- 1419910 TI - A common set of nuclear factors bind to promoter elements regulated by the retinoblastoma protein. AB - A 30-base pair element within the c-fos promoter, termed the RCE (retinoblastoma control element), has previously been shown to be the target of transcriptional regulation by the product of the retinoblastoma (Rb) gene. We have identified three nuclear proteins [retinoblastoma control proteins (RCPs)] that complex with this promoter element in vitro. The Rb gene does not appear to encode the RCPs as the expression of Rb in vivo does not correlate with RCE-RCP complex formation in vitro. A single binding site for the RCPs within the c-fos RCE was identified, and the nucleotides required for protein-DNA complex formation were defined. Similar sequences are found in the promoters of two additional genes that are regulated by Rb (c-myc and TGF-beta 1), and binding assays demonstrate that the RCPs also interact with these elements. Linkage of the c-fos RCE to the herpes simplex virus thymidine kinase promoter led to a 4-fold stimulation of expression in transient transfection assays. Mutations within the RCP binding site that abrogate stable interaction of the RCPs with the RCE in vitro block RCE transcriptional activity in vivo. Our results suggest a role for the RCPs in RCE dependent transcription and the regulation of transcription by the Rb protein. PMID- 1419911 TI - Persistent expression of the tumor suppressor gene DCC is essential for neuronal differentiation. AB - Cell differentiation is associated either with a complete loss of proliferative potential or with a change in growth requirements. Neoplastic transformation may result from the activation of oncogenes that support growth or from inactivation or loss of tumor suppressor genes, which are thought to regulate differentiation. To examine the relationship between tumor suppressor genes and cell differentiation, we chose the gene "deleted in colorectal cancer" (DCC) and studied its role in a pheochromocytoma cell line, PC-12, using antisense RNA as well as antisense oligonucleotides to DCC. When exposed to nerve growth factor for several days, PC-12 cells develop long dendrites. This morphological change follows the transient expression of immediate early genes and is associated with an up-regulation of DCC. Interestingly, if the up-regulation of DCC was counteracted using an antisense RNA technique, the morphological changes were prevented, but the other parameters of the nerve growth factor response were unaffected. Moreover, when DCC expression was inhibited by antisense oligonucleotides to DCC in nerve growth factor-differentiated cells, the neuron like phenotype was reversed. Our results demonstrate that the gene DCC is involved in a distal segment of neural differentiation and provide the first direct evidence that a tumor suppressor gene plays a role in cell differentiation. PMID- 1419912 TI - Neuronal differentiation triggered by blocking cell proliferation. AB - Treatment of the neuroblastoma cell line SHSY5Y with nerve growth factor (NGF) resulted in limited neurite extension, but proliferation continued. However, SHSY5Y cells treated with NGF and a pulse of the DNA polymerase alpha and delta inhibitor aphidicolin showed dramatic neuronal differentiation. Few differentiated cells were observed immediately following the NGF-aphidicolin treatment; however, continued treatment of the cells with NGF in the ensuing week resulted in extension of long neurites (> 400 microns). Neurite extension was not observed for cells treated with aphidicolin alone. Hence, aphidicolin and NGF act synergistically to induce differentiation of SHSY5Y cells. If maintained in NGF, the differentiated cells were stable for at least 1 month and displayed many neuronal characteristics. They were mitotically inactive, and, in contrast to control or NGF-treated cells, the differentiated cells required NGF for survival. The cells expressed multiple microtubule-associated proteins (MAP), including MAP 1A, MAP 1B, and tau. There was expression of synaptic vesicle antigens synaptophysin and SV2, but not synapsin Ia/b or synapsin IIa/b. Both hydroxyurea and thymidine, which inhibit synthesis of nucleotides, act synergistically with NGF to induce differentiation of SHSY5Y cells. Since aphidicolin, hydroxyurea, and thymidine are chemically unrelated, we conclude that these drugs enhance NGF induced differentiation by blocking cell proliferation and not through an unrelated side effect. The model suggested by these studies is that differentiation is triggered by two simultaneous signals: NGF and cessation of cell proliferation. PMID- 1419913 TI - Down-regulation of cell cycle control genes by ionizing radiation. AB - The cellular responses to ionizing radiation include growth arrest, DNA repair, and lethality. However, little is known about the signaling events responsible for these responses. The present studies have examined the effects of ionizing radiation on the expression of genes involved in cell cycle control. The results demonstrate that the treatment of asynchronous cells with 20 Gy ionizing radiation is associated with transient down-regulation of the cdc2, cyclin A, cyclin B, and cdc25 genes. This effect was associated with transient induction of the c-jun gene. RNA stability studies demonstrate that the down-regulation of gene expression following ionizing radiation exposure is at least in part due to a decrease in transcript half-life. Other studies were performed with elutriated cells enriched for populations in G1 and S phases. Treatment of G1 enriched cell populations with 10 Gy resulted in a selective decrease in cyclin B mRNA levels, whereas this effect on cyclin B expression was less pronounced at 5 Gy and undetectable at 1 Gy. Similar results were obtained with S phase enriched cells. Taken together with clonogenic survival studies, these findings indicate that down-regulation of cell cycle control gene expression is associated with lethality, whereas lower doses of ionizing radiation have little, if any, effect on the expression of these genes. The findings also suggest that DNA damage may activate signaling events which regulate expression of cell cycle control genes. PMID- 1419914 TI - Expression of the growth factor-inducible immediate early gene cyr61 correlates with chondrogenesis during mouse embryonic development. AB - cyr61 is a growth factor-inducible immediate early gene initially identified in serum-stimulated mouse fibroblasts. It encodes a member of an emerging family of cysteine-rich secreted proteins that includes a connective tissue growth factor. We show here that cyr61 is expressed in the developing mouse embryo and extraembryonic tissues. In the placenta, cyr61 is expressed in regions of trophoblastic origin, including the ectoplacental cone and the trophoblastic giant cells. In the midgestation embryo, cyr61 is expressed in the smooth muscle vessel walls of the arterial circulatory system. Most notably, expression is found in developing cartilaginous elements, including the limbs, ribs, and prevertebrae. In addition, regions of the chondrocranium and craniofacial elements, such as Meckel's cartilage, also express cyr61. Thus, cyr61 transcript is found in mesenchymal cells of both mesodermal and ectodermal origin during their differentiation into chondrocytes. The temporal and spatial regulation of cyr61 expression and the biochemical features of its encoded protein suggest that cyr61 may be important for the normal growth, differentiation, or morphogenesis of the cartilaginous skeleton of the embryo. PMID- 1419915 TI - Medical technologies in developing countries: a pilot programme for the setting up of a regional centre for maintenance of medical equipment in Ethiopia. AB - In the last years a new approach to cooperation programmes with developing countries has been followed. It critically considers cooperation as donation and makes a big contribution to cooperation for the development of developing countries. For such reasons some topics such as 'education' and the 'management of the health services and technologies' have become more important than in the past. The authors report, first on some general aspects of the cooperation programmes in this field and, secondly, on some experiences relating to a cooperation programme for the management of medical technologies in Ethiopia. PMID- 1419916 TI - A non-linear method for estimating the alpha generators from an EEG over the scalp. AB - A method is developed to estimate the frequency feature of alpha generators from EEG signals of different derivation. This method is based on principal component analysis and a constrained non-linear optimization technique. Results of the method gives a variation range of the power spectrum. Experimental results for estimating the generator spectra of the brain alpha activity in anterior and posterior regions over the scalp are shown. Finally, the noise problem with this method is also discussed. PMID- 1419917 TI - A new ensemble averaging technique in impedance cardiography for estimation of stroke volume during treadmill exercise. AB - In this study, a new ensemble average technique is developed to measure cardiac output during treadmill exercise. Each dz/dt peak is used as a starting point for ensemble averaging, instead of the conventionally used R point of the ECG, in order to prevent the peak dz/dt waveform (C point) from smoothing, which results in increased dz/dtmax. The R-Z interval from the R point of the ECG to the peak dz/dt varies for each heart beat especially during strenuous exercise. Signal-to noise ratios of five subjects obtained with the new technique are 0-32.6% higher than those obtained with the conventional technique at rest and during four levels of treadmill exercise. Power spectral densities of the averaged dz/dt waveforms by the peak dz/dt and R point references are also analyzed. Stroke volumes of the five subjects averaged by the peak dz/dt are 0-23.5% higher than those obtained by the R point at rest and during four levels of exercise. PMID- 1419918 TI - Research on the main elements influencing blood pressure measurement by pulse wave velocity. AB - There have been considerable errors in non-invasive continuous beat-by-beat blood pressure (BP) measurement using the pulse wave velocity (PWV). To solve the problem, an in vivo study using 10 dogs was performed. The PWV-BP correlation under intact neuro-humoral factors was compared with that under the factors to be partly eliminated and the PWV-BP regularities were investigated using 10-beat average data. It was confirmed that the vasomotion and the viscoelasticity of vascular smooth muscles are the main elements influencing PWV-BP correlation through changing the elasticity of the arterial wall, and result in a 'shift' and 'zigzag swings' in the PWV-BP relationship so as to lower the PWV-BP correlation. By choosing large arteries and modifying the PWV algorithm, linear correlation coefficients of 0.97 +/- 0.027 and standard errors of the BP estimate of 5.29 +/- 2.84 mm Hg were obtained. The study suggests that the error could be further reduced by simultaneously measuring some related parameters. PMID- 1419919 TI - An isolation power supply by phototransmission. AB - An isolation power supply by phototransmission was proposed, and the conversion efficiency and the electric characteristics of a prototype of the power supply unit were estimated. Infrared light emitting diodes (LEDs) and single-silicon crystal solar cells were used as light sources and photovoltaic cells, respectively. A maximum conversion efficiency of 3.9% was achieved. The constant output voltage feedback system, which detects the change of the output voltage of the solar cells and controls the driving current of the LEDs, operates this power supply at maximum conversion efficiency independent of loads. The liquid-cooling structure of the power supply unit can keep the conversion efficiency nearly constant independent of the input power. The fabricated power supply has little capacitive leakage current and negligibly small internal noise. PMID- 1419920 TI - Spectral 'noise' and ultrasonic tissue characterization. AB - The spectral fluctuations of each realization of echo signals are usually regarded as a noise to be rejected. However, a significant amount of texture information is hidden within such 'noise'. In fact, it allows us to distinguish three classes of breast tissue, chosen for their distinctive histology. PMID- 1419921 TI - An 8086-based Holter arrhythmia monitor. AB - Holter monitoring is a technique which involves the use of a specialized recorder to record and analyze the ECG of an ambulatory subject for a duration up to 24 h. It is used for persons who have generally normal ECG, but who experience heart disorders under some particular stress conditions. This paper describes the design of an 8086-based Holter monitor using state-of-the-art technology. The old concept of analog signal processing and cassette recording has been replaced by digital signal processing and solid state memories. The main features of the new monitor, as compared with conventional ones, is its intelligence to detect and record arrhythmias which are of clinical importance. Emphasis was placed on miniaturization and minimization of the power consumption while designing the monitor. PMID- 1419922 TI - Effects of battered women's early responses on later abuse patterns. AB - Abused women (N = 234) were interviewed using a structured questionnaire to determine whether violence increases during the course of an abusive relationship. Comparisons were made between women with short-term violence and long-term abusive relationships to assess whether strategies used by victims during early incidents affected the duration of the violence. Women out of the relationship were also contrasted with women still in the relationship. The data supported the picture of increasing abuse for 18 months with a relatively stable rate from then on. The number of forms of abuse and the severity of them tended to quickly increase over early events. Women with short-term violence were more likely to make plans following early incidents, typically involving changing the marital situation. Whether experiencing short-term or long-term abuse, battered women perceived their own sanctions on the abusers as responsible for the cessation of the violence. Continued investigation is necessary to replicate these findings and to identify strategies for reducing violence while women are in the relationship. PMID- 1419924 TI - Perceived credibility of children's sexual abuse allegations: effects of gender and sexual attitudes. AB - We investigated whether sex role stereotyping, adversarial sexual beliefs, acceptance of interpersonal violence, sex of the subject, characteristics of the child (age, sex), and characteristics of the alleged perpetrator (stranger, father) affect judgments of the credibility of children's reports that they have been sexually abused. Two hundred and fifty-five college students in a 3 x 2 x 2 factorial arrangement were given the Burt (1980) scales and asked to read a short vignette in which a child alleged that he/she was sexually abused and the accused male denied the abuse. Although the vast majority of subjects indicated that they believed the child was telling the truth, females rated the child's credibility significantly higher than males F(1, 253) = 6.29, p = .01226. No other significant relationships were found. The results imply that the vast majority of individuals in a college sample tended to believe children's sexual abuse allegations and that this credibility assessment is not influenced by characteristics of the child or perpetrator examined in this study. Implications of the truncated range of the dependent variable and of the Burt scales are discussed. PMID- 1419923 TI - An evaluation of a secondary school primary prevention program on violence in intimate relationships. AB - A large-scale primary prevention program for wife assault and dating violence was evaluated, employing a measure of attitudes, by means of the London Family Court Clinic Questionnaire on Violence in Relationships. The target audience comprised all students in four high schools. A brief intervention, including a large group presentation on wife assault and dating violence, followed by classroom discussion facilitated by community professionals was instituted. Attitudes, knowledge and behavioral intentions were assessed prior to intervention, immediately afterward, and at five to six weeks postintervention, in a stratified classroom level random sample of the participants. Significant positive attitude, knowledge, and behavioral intention changes were found at posttest, and the majority of these were maintained at delayed follow-up. Striking sex differences were found, with females consistently showing better attitudes than males. A 'backlash' effect was noted among a small number of males after the intervention. It was hypothesized that this group may already be involved in abusive behavior and require secondary, rather than primary, prevention. Students reported a high level of awareness of and experience with violence in their own and their friends' dating and family relationships, and overwhelmingly endorsed primary prevention of relationship violence in the schools. PMID- 1419925 TI - The impact of professional football games upon violent assaults on women. AB - The relationship between the timing and outcomes of the Washington Redskins' football games and the frequency of admissions to hospital emergency rooms in northern Virginia is investigated. An OLS time series analysis is conducted, controlling for days of the week, months, years and special holidays for 1988 1989. The results indicate that the frequency of admissions of women victims of gun shots, stabbings, assaults, falls, lacerations and being struck by objects increases when the team wins. We hypothesize that many of these injuries are the result of battering and that having a favorite team win may act as a trigger for assault in some males. We suggest that viewing the successful use of violet acts may give the identifying fan a sense of license to dominate his surroundings. PMID- 1419926 TI - The moderating impact of social support following childhood sexual abuse. AB - The role of social support in moderating the impact of childhood sexual abuse on adult psychological adjustment was examined. Subjects included 475 women, age 18 45, some of whom were currently receiving treatment, others who were not. Women in the treatment group were receiving therapy for either alcoholism, for being battered, or for mental health problems. The comparison group was drawn from two sources: a random household sample and a sample of women attending drinking driver classes. Among both groups, women who had been sexually abused exhibited more psychological symptoms and lower self-esteem compared to those who were not abused. Latency of disclosure of childhood sexual abuse had no impact on long term consequences of the abuse for either the treatment or the comparison group. However, among women in the comparison group, those who experienced supportive reactions following disclosure of sexual abuse had fewer psychological symptoms and somewhat higher self-esteem relative to those who did not receive support. Social support had no apparent effect on the long-term adjustment of women in the treatment group. Possible explanations for this pattern and directions for future research are discussed. PMID- 1419928 TI - Brightness versus apparent contrast. 1: Incremental and decremental disks with varying diameter. AB - This study describes the matching of the brightness and of the apparent contrast of foveal disks, presented as an increment or decrement with varying diameter against a 300 cd.m-2 background. If the brightness in the centre of the disks is matched with a constant reference brightness, the well-known spatial Broca-Sulzer phenomenon is obtained. This effect is not found if the apparent contrast of the disks is matched instead. All matching results and detection thresholds indicate that luminance increments and decrements are processed asymmetrically by the visual system: for decrements the threshold curve and curves of isobrightness as well as apparent iso-contrast are all shifted towards larger disk radii relative to those for increments. Two nonlinear single-channel models are tested against the data. PMID- 1419927 TI - Conventional and delinquent activities: implications for the prevention of violent victimization among adolescents. AB - While age is one of the most important correlates of an individual's risk of violent victimization, research regarding the victimization of adolescents is relatively meager. Using two well-known national data sources and an analytical framework guided by lifestyle/routine activities theories, we describe the relationships between activity involvement and the risk of assault and robbery victimization among adolescents in the United States. Several findings relevant to victimization prevention emerge. First, we find that certain adolescent activities are related to risk of violence. Youth who engage in delinquent activities experience the highest risk of assault and robbery victimization. Second, we find very few conventional activities which protect adolescents from victimization net of background factors (e.g., gender, race, family structure) or offending levels. We discuss the implications of these findings for programs directed at reducing violent victimization among adolescents and for lifestyle/routine activities theories of victimization. PMID- 1419929 TI - Measurement of the 2D affine Lie group parameters for visual motion analysis. AB - A class of linear operators is presented for estimating the local components of 2D translation, dilatation, rotation, and the shear/deformations which span the six degrees of freedom of motion of arbitrarily textured surfaces. This results in a model of visual motion analysis which proposes that the local transformations in the image are analysed by decomposing them into the six one parameter subgroups of the 2D affine group. Each of the required invariant integral operators are easily specified by the characters of these six subgroups. The 2D affine group, however, does not have a simple structure. It is a Lie group which possesses a semi-direct product manifold, and classical harmonic analysis cannot proceed unless some mechanism is prescribed to isolate the 2D 'general linear' transformations from the 2D translations. It must also do so using measures which receive only local support from the image, since the global affine group model is only valid tangentially. A form of 'active perception' is thereby implicated; it is proposed that spatial indexing and 2D tracking is needed in order to form reliable estimates of 3D motion parameters using local operators in a data-driven fashion. PMID- 1419930 TI - Visual search for oriented lines: the role of angular relations between targets and distractors. AB - Subjects can perform parallel visual search for an item of unique orientation when it is presented on a background texture composed of lines of two other orientations. A number of cues can be used to speed this search. It helps if the target has a unique categorical status (e.g., it is the only 'steep' item) (Wolfe et al., J. Exp. Psychol. Hum. Percept. Perf. 18, 34-49 1992). It helps if the two background orientations are symmetrical about a vertical axis (Wolfe and Friedman Hill, Psychol. Sci. 3, 194-198, 1992). The experiments presented here show that it helps if the angles formed by the target with one of the distractor types are smaller than the angles formed by the two distractor orientations. These results illustrate that stimulus similarity is a complex concept even for a simple feature like orientation. PMID- 1419931 TI - Phase shifts and the square-wave illusion. AB - When observers view a vertical triangle-wave luminance profile, they often report a square-wave illusion with a depth component, resembling a corrugated surface. Alternate bars seem to be in front of or behind adjacent bars and the surface appears to be illuminated from the right or left. These perspectives alternate with continuous viewing. One explanation for this illusion stems from the notion of instability among phase-selective mechanisms. Two experiments (1 and 3) were designed to determine whether systematic phase shifts introduced between the fundamental and the odd harmonics of the waveform would lead to a systematic bias of the illusion. The results indicated that a significant bias occurred when a phase shift as small as 9 deg was introduced, and that the bias from the phase shifts was more powerful than previous reports of drift-induced bias. There was a highly significant effect of direction of phase shift and the corresponding perceived direction of illumination. Another experiment (2) was designed to determine if illusional cues within the phase-shifted profiles aided phase discrimination. The results indicated that experienced subjects, presumably using cues within the profiles, discriminated between the stimuli significantly better than did naive subjects. These data support the role of phase in the square-wave illusion, but they also raise questions about the role of contrast changes in local regions of the stimulus. PMID- 1419932 TI - Abstract processes in texture discrimination. AB - In this study some experiments on texture segmentation are reported using the local Gabor power spectrum. The techniques applied are: (1) supervised pixel classification; (2) boundary detection by spectral dissimilarity estimation; (3) region-based segmentation based on Gaussian spectral estimation; and (4) the same as (3) but based on central moments of the local spectrum. It is shown that very acceptable-to-excellent results can be obtained. It is argued, however, that the shortcomings of region-based and boundary-based approaches require that both processes should act in parallel, not only in digital image processing but also in the modelling of visual perception. PMID- 1419934 TI - Symptomatology and the prediction of social skills acquisition in schizophrenia. AB - The relationship between patient symptomatology and the acquisition of social skills during an inpatient social skills training program, and the maintenance of skills at a one-month followup, were examined in a sample of recently hospitalized schizophrenic and schizoaffective disorder patients. Subtypes of patients with enduring Thought Disorder (vs. no enduring Thought Disorder) or enduring Anergia (vs. no enduring Anergia) on the BPRS during the treatment period were compared in their response to the social skills training intervention. Patients with enduring Thought Disorder acquired skills at the same rate as patients without Thought Disorder, but were unable to retain their skills at followup, in contrast to their counterparts. Enduring Anergia was not related to either the acquisition or maintenance of social skills. The results were unaffected when memory was statistically controlled. The findings suggest that patient symptomatology may be an important factor mediating the efficacy of social skills training interventions. PMID- 1419933 TI - Normal eye tracking is associated with abnormal morphology of medial temporal lobe structures in schizophrenia. AB - Eye tracking and brain morphology assessed by magnetic resonance imaging were examined in 48 patients in their first episode of schizophrenia and in 15 normal controls. Schizophrenic patients showed higher rates of eye tracking dysfunction and more abnormal brain morphology involving the lateral ventricles, medial temporal lobe (MTL) structures and the frontal-parietal cortex than controls. Enlargement of the lateral ventricles and global rating of abnormal brain morphology were significantly more prevalent in male schizophrenics than female schizophrenics. These findings indicate that abnormalities in a variety of brain regions are present in some schizophrenics during the period shortly after the first hospitalization and could not be a function of treatment or chronic illness. We found no relation between abnormal eye tracking and any single feature of abnormal brain morphology. However, normal eye tracking was significantly associated with MTL abnormalities in schizophrenics, reflecting an inverse association between quality of eye tracking and degree of abnormality in MTL structures. These results suggest that abnormal eye tracking is not mediated by the same processes that lead to structural brain anomalies in schizophrenia. PMID- 1419935 TI - Left-handed first-episode, neuroleptic-naive schizophrenic patients have a higher prevalence of autoantibodies. AB - Using standard immunological techniques, sera from first-episode, neuroleptic naive schizophrenic patients (n = 51) and age, race and sex matched healthy controls (n = 51) were screened for seven common autoantibodies. Significantly more left-handed (67%) than right-handed (23%) schizophrenic patients had autoantibodies (p = 0.011). Left-handed schizophrenic patients were six times more likely than right-handed patients or controls and four times more likely than left-handed controls to test positive for autoantibodies (p = 0.012). These data suggest that disease and sinistrality contribute to the excess of autoantibodies in schizophrenia. PMID- 1419936 TI - The Patient Rejection Scale in an Israeli sample: correlations with relapse and physician's assessment. AB - The Patient Rejection Scale (PRS), which was developed to assess the feelings of rejection that relatives experience toward mental patients, was administered to a sample of 50 family members living with schizophrenic outpatients in Jerusalem, Israel. PRS response distribution was similar to that reported for a New York City sample. Total rejection scores were significantly correlated with a number of demographic variables and with the treating physician's assessment of the degree of rejection, hostility and criticism of the respective family members. Physician's rating of emotional over-involvement did not correlate with PRS scores. Both PRS and treating physician's ratings correlated significantly with course of illness parameters. The findings and their implications are discussed in the context of expressed emotion (EE) research. PMID- 1419937 TI - Estimating daily urine volume in chronic psychosis. PMID- 1419938 TI - Biography of Louis Gaston Labat, M.D. PMID- 1419939 TI - 1992 Labat Lecture. Toward the mathematization of spinal anesthesia. PMID- 1419940 TI - Perioperative analgesia with subarachnoid sufentanil administration. AB - BACKGROUND AND OBJECTIVES: Thirty-seven ASA Physical Status I parturients undergoing elective cesarean delivery were evaluated to determine the effects of subarachnoid sufentanil administration. METHODS: This study was carried out in a randomized, double-blind fashion. All patients received 1.4 ml 0.75% bupivacaine with 8.25% dextrose following 10 micrograms, 15 micrograms, or 20 micrograms sufentanil, or 1 ml of normal saline containing no sufentanil. Onset and duration of sensory and motor anesthesia, duration of complete analgesia, duration of effective analgesia, and intraoperative parenteral opioid requirements were evaluated. Incidence of side effects such as respiratory depression, pruritus, nausea, and vomiting were evaluated. RESULTS: Duration of complete analgesia and duration of effective analgesia were prolonged significantly in all patient groups receiving sufentanil as compared to control groups receiving no narcotic. Pruritus was significantly increased in patient groups receiving subarachnoid sufentanil. Respiratory depression was not observed in any patient studied. One- and five-minute Apgar scores; umbilical, venous, and arterial blood gas results; and Early Neonatal Neurobehavioral Scale results were all within normal limits and were not significantly different among the groups. PMID- 1419941 TI - Efficacy of subarachnoid morphine in a community hospital. AB - BACKGROUND AND OBJECTIVE: Two hundred seventy-five patients who underwent major surgery and received subarachnoid morphine for postoperative pain relief were prospectively studied to establish the benefits of its routine use in a community hospital. RESULTS: Seventy-nine percent of all patients had a satisfactory analgesic-free interval of 18 hours, and postoperative analgesics were unnecessary for the first 24 hours in 56% of all patients. Pruritus developed in 26% of all patients, 16% experienced nausea, vomiting, or both, and 4% experienced urinary retention. There were no cases of respiratory depression. Ninety-two percent of all patients were managed on the medical/surgical floors without incident, and 90% of the patients were satisfied with their results. CONCLUSION: It was shown that, when there are properly trained floor nurses, subarachnoid morphine (0.1-0.4 mg) can be an effective, safe, and simple method for postoperative pain control in a community hospital. PMID- 1419942 TI - Comparison of Sprotte and Quincke needles with respect to post dural puncture headache and backache. AB - OBJECTIVE: The objective of this study was to compare 24-gauge Sprotte and 25 gauge Quincke needles with respect to post dural puncture headache and backache. METHODS: Three hundred ASA Physical Status I or II patients scheduled for minor orthopedic or urologic operations under spinal anesthesia were chosen for this randomized, prospective study at a university hospital and a city hospital. Anesthetic technique, intravenous fluids, and postoperative pain therapy were standardized. Patients were randomly divided into three equal groups. Spinal anesthesia was performed with either a 24-gauge Sprotte needle or a 25-gauge Quincke needle with the cutting bevel parallel or perpendicular to the dural fibers. RESULTS: Anesthesia could not be performed in three cases with the Sprotte needle and in one case with the Quincke needle. The most common complications were post dural puncture backache (18.0%), post dural puncture headache (8.2%), and non-postural headache (6.7%). No major complications occurred. The Quincke needle with bevel perpendicular to the dural fibers caused a 17.9% incidence of post dural puncture headache. The Quincke with bevel parallel to the dural fibers and the Sprotte needles caused similar post dural puncture headache rates (4.5% and 2.4%, respectively). Other factors associated with post dural puncture headache were young age, early ambulation, and sedation during spinal anesthesia. There were no significant differences between needles in the incidence of post dural puncture backache. CONCLUSION: Our data indicate that Quincke needles should not be used with the needle bevel inserted perpendicular to the dural fibers. The Sprotte needle does not solve the problem of post dural puncture headache and backache. PMID- 1419943 TI - Technical and light microscopic comparison of four different small-diameter catheters used for continuous spinal anesthesia. AB - BACKGROUND AND OBJECTIVES: Recently several manufacturers developed ultra-thin catheters for continuous spinal anesthesia. Their use may be associated with technical problems. METHODS: Four spinal catheters [Preferred Medical 28-gauge and 32-gauge (polyurethane), Kendall CoSpan 28-gauge (nylon), and Microspinal 32 gauge (polyimide)] were compared in 41 patients who underwent knee or hip operations. Difficulties in using the catheters were recorded, and after their removal, the catheters were examined by light microscopy. RESULTS: The insertion of the 28-gauge catheters was always successful. However, five of 11 of the 32 gauge polyurethane and one of ten of the 32-gauge polyimide catheters could not be inserted. Plain 0.5% bupivacaine (2-6.5 ml) was administered, and the median pinprick analgesia level varied between T4 (28-gauge nylon) and T7 (other groups). During removal, one of ten of the 28-gauge nylon, four of ten of the 28 gauge polyurethane, and all six 32-gauge polyurethane catheters stretched. Two of six of the 32-gauge polyurethane catheters broke, but no fragment remained in any patient. Microscopic examination revealed deposits of fibrinous material on the tips of all polyurethane and polyimide catheters and on one nylon catheter. One polyimide catheter ruptured 15 cm from the tip. No signs of tearing or lost pieces of catheter material were observed by light microscopy. CONCLUSION: The use of the 32-gauge polyurethane catheter was associated with problems that limit its clinical usefulness. Nylon and polyimide catheters with stainless steel stylets were more resistant to stretching. The nylon catheter was most resistant to adhesion of fibrinous material. PMID- 1419944 TI - Continuous pump pressures cannot be used to identify catheter tip migration into the subarachnoid space. AB - BACKGROUND AND OBJECTIVES: Migration of an epidural catheter into the subarachnoid space is a potentially lethal complication of continuous epidural anesthesia. We evaluated the use of pump pressure measurement during infusion in detecting such an occurrence. METHODS: Pump pressures at two flow rates (P1 and P10) and epidural space pressure (P0) were measured hourly in eight consecutive ASA Physical Status I parturients receiving continuous epidural anesthesia and compared to those of a patient whose catheter migrated into the subarachnoid space. In addition, total resistance to infusion (Rtot) was calculated as the slope of the least squares regression line linking pressure and flow. Epidural resistance (Repi) was computed as the difference between total resistance and catheter resistance; Repi = Rtot - Rcath. RESULTS: In epidural catheters, average P0 and P10 were 13 +/- 4 mmHg and 23 +/- 4 mm Hg, respectively, and did not change over time. Rtot and Repi averaged 960 +/- 180 RU and 980 +/- 120 RU, respectively. Pump pressures in the subarachnoid catheter were 10 mmHg for P0 and 20 mmHg for P10, while Rtot was 1000 RU. CONCLUSIONS: We conclude that epidural and subarachnoid space resistance is essentially zero and the pump pressure in the system is used to overcome the catheter resistance. Both spaces offer the same total resistance to infusion and, therefore, pump pressure will not change when a catheter migrates into the subarachnoid space. PMID- 1419945 TI - Brachial plexus block with the nerve stimulator: motor response characteristics at three sites. AB - BACKGROUND AND OBJECTIVES: Differences in motor response patterns, minimum electrical currents, and success rates using a nerve stimulator for brachial plexus block were determined for the interscalene, supraclavicular, and axillary approaches. METHODS: Supervised, resident physicians performed 106 brachial plexus blocks. For each block, the minimum stimulating current, the strongest joint motion at the minimum current immediately before local anesthetic injection, presence or absence of other joint motion, and anesthetic success or failure were recorded. RESULTS: In the interscalene group (n = 43), strongest joint motions clustered at the shoulder (40%) and elbow (54%). In the supraclavicular group (n = 29), strongest joint motions distributed bimodally at the elbow (62%) and fingers (31%). In the axillary group (n = 34), strongest joint motions clustered at the wrist (35%) and fingers (61%). Overall, concurrent, weaker joint motion was observed in 26% (p not significant). Overall, the minimum current producing visually observable or palpable upper extremity motor responses was 0.69 +/- 0.02 mA (mean +/- SEM, range 0.2-1.5). No significant differences were found for minimum currents by site of approach, presence or absence of weaker joint motion, or success or failure of anesthesia. The overall success rate was 89%, with the rate being 91% for interscalene, 97% for supraclavicular, and 79% for axillary approaches (p not significant). Within the axillary group, elbow flexion as the strongest joint motion was a significant predictors of failure compared with other responses (p < 0.05). CONCLUSIONS: Localization of the brachial plexus with the nerve stimulator is equally effective at the interscalene, supraclavicular, and axillary sites. Current values in the range reported have no predictive value for success. Advantages of the nerve stimulator for brachial plexus block include an objective endpoint and continuous feedback. PMID- 1419946 TI - Selective block of nerves in the axillary approach to the brachial plexus. AB - BACKGROUND AND OBJECTIVE: Optimal surgical conditions for flexor tendon tenolysis in the hand were achieved by ulnar, radial, and musculocutaneous nerve block at the axilla combined with median nerve block at the wrist. RESULT: Because the median nerve function proximal to the wrist was preserved, the patient was able to flex the finger intraoperatively. CONCLUSION: Palpation of nerves together with a nerve stimulator were used to localize the nerves accurately. PMID- 1419948 TI - Is peribulbar block safer than retrobulbar? PMID- 1419947 TI - Headache from intracranial air after a lumbar epidural injection: subarachnoid or subdural? AB - BACKGROUND AND METHODS: There is a growing awareness of the possibility of headache resulting from intracranial air secondary to identification of the epidural space by loss of resistance using air (LOR-A). Most reported cases have been attributed to subarachnoid air passage. A case is described of sudden headache following LOR-A. RESULTS: Various features of the case suggest that the passage of air to the head was subdural rather than subarachnoid. CONCLUSIONS: Recovery was uneventful. PMID- 1419949 TI - An argument against the use of the nerve stimulator for peripheral nerve blocks. PMID- 1419950 TI - Quaternary structure and assembly process of the T cell receptor. AB - The human immune system contains T and B lymphocytes which respond in an antigen specific manner to foreign antigens. These foreign antigens are recognized by multimeric receptors expressed on the cell surface of T and B lymphocytes. The subunits that make up the T and B cell receptor complexes have been identified, but their stoichiometries and positions in the complex remain to be resolved. Elucidation of the quaternary structures is necessary to understand the molecular basis of signal transduction events which follow antigen recognition and will contribute to the design of drugs that can modulate T and B cell responses. Here, I will discuss recent insights into the quaternary structures of the TCR and BCR and the striking similarities between the two, both in the structures of the subunits and in the overall quaternary structures. In addition, the intracellular assembly processes of these receptor complexes will be discussed, as well as the recent realization that these processes appear to be mediated by house-keeping proteins that transiently bind to partial TCR and BCR complexes. Similar to the role of BiP which mediates assembly processes of B cell immunoglobulins, a recently identified intracellular protein of 90 kD, called IP90, appears to play a role in TCR and BCR assembly processes. Analyses of the IP90 protein might contribute not only insight into the folding and assembly processes in lymphocytes, but also into those of newly synthesized proteins in many different cell types. PMID- 1419952 TI - Recent trends in research on differentiation of hematopoietic cells and lymphokines (hemopoietins). AB - A recent trend in hematological research fields has been to isolate and characterize hematopoietic stem cells/progenitors and their growth factors (hemopoietins) to gain a much better understanding of the nature of the stem cell and the mechanisms regulating its development. It is generally accepted that all the various types of blood cells develop from a single progenitor called a hematopoietic stem cell. Quantitative studies of the function of hemopoietic stem cells began two decades ago with the development of a spleen colony assay, and then, clonal cell culture techniques for committed progenitors were developed with several models for hematopoietic differentiation being proposed. Within the last few years, some hormones have been discovered that are known as hematopoietic growth hormones or hemopoietins, each of which is of protein nature and causes specific classes of blood cells to be made and primed. These hormones also enhance the function of the mature cells, the genes of which have recently been cloned. On the other hand, long-term bone marrow culture has recently permitted detailed investigations of the relationship between hematopoietic cells and the microenvironment in which they are found, e.g. stromal cells, in vitro, relating to the regulation of cell proliferation and differentiation. Further, in hematological fields, other bioactive factors including differentiation-inducing compounds, e. g. bioactive glycosphingolipids, and leukocyte-endothelial cell recognition molecules (adhesion receptors) have been discovered, the molecular mechanism(s) of which have yet to be elucidated. This communication focuses on recent advances in research on soluble hemopoietins and other bioactive factors relating to differentiation-induction and to cell-to-cell recognition. PMID- 1419951 TI - Hodgkin's disease derived cell lines: a review. AB - A number of so-called "HD cell lines" have been established over the last 10-15 years (Table 1). Or those 15 cell lines we studied, only the cell lines CO, DEV, HD-70, HDLM, KM-H2, L-428, L-540 and SUP-HD1 can be regarded to represent true HD cell lines. According to the immunostaining results and molecular genetic data, these 8 cell lines can be assigned either to the T-cell lineage (CO, HDLM, L-540) or B-cell lineage (DEV, HD-70, KM-H2, SUP-HD1). With the data currently available, the cell lineage origin of L-428 cannot be unequivocally determined, but appears to be lymphoid. All but one of these eight HD cell lines have been established from patients with the nodular sclerosis subtype. Therefore, the conclusions drawn from the in vitro studies are limited to this histological subtype of HD. It is conceivable that culture conditions select for a particular type of cell that will survive. The state of differentiation of these HD cell lines remains unclear due to the incomplete expression of T- or B-cell antigens. The in vitro cells and the in vivo H-RS cells share, however, the expression of the unique activation markers CD15, CD25, CD30, CD71 and HLA-DR. Recently published data indicate that the HD cell lines express and produce a large number of cytokines. Multiple non-random chromosomal abnormalities and the expression of various proto-oncogenes are also new and exciting findings and certainly deserve further study. In summary, although the cultured cells are not unequivocally proven to be the direct progeny of in vivo H-RS cells, several continuous HD cell lines have been established that display a variety of phenotypical features identical or similar to those of their presumed in vivo counterparts. Surface marker, molecular genetic and other features suggest a T- or B-cell derivation. An extrapolation of these conclusions would point to a lymphoid origin of H-RS cells. Whether H-RS cells can originate from other cell types such as monocytes/macrophages or reticulum cells, cannot be answered with the currently available HD cell lines. PMID- 1419953 TI - Human T lymphotropic virus type-I (HTLV-I) immortalizes human T cells in vitro- its implication in the pathogenesis of adult T cell leukemia (ATL). AB - HTLV-I is the first human retrovirus that was isolated from a patient with T-cell malignancy in 1980 in the United States. HTLV-I is detected in most patients with adult T cell leukemia (ATL) and healthy carriers, who are frequently found in the southwestern parts of Kyushu and Shikoku Districts. HTLV-I-infected cells express IL-2 receptors, and HTLV-I-infected T cell lines can be established from most of ATL patients in culture in the presence of IL-2. Furthermore, these IL-2 dependent T cell lines often begin to proliferate in the absence of IL-2 and to not respond to IL-2, despite IL-2 receptors on their cell surface, thus mimicking ATL cells in vivo. These findings suggest that HTLV-I is an etiological agent of ATL. In this mini-review, the T cell immortalizing activity of HTLV-I in vitro, with special reference to the evolution of ATL cells based on our results, is described. PMID- 1419954 TI - [Key points and problems concerning chemosensitivity tests, with special reference to MTT assay]. AB - Recently, the semiautomated tetrazolium-based MTT colorimetric assay have been used to measure chemosensitivity. We also have been used this assay for 4 ovarian clear cell carcinoma cell lines to investigate the chemosensitivity of this tumor. In this study, several problems have been faced to be solved. In this paper, we pointed out these problems and indicated solutions. PMID- 1419955 TI - The expression of the mouse VpreB/lambda 5 locus in transformed cell lines and tumors of the B lineage differentiation pathway. AB - The expression of RNA transcripts from two pre B lymphocyte related genes, VpreB and lambda 5, has been studied in a series of transformed cell lines which appear frozen at different states of B lineage differentiation, from early progenitors to surface Ig positive B cells. In the HAFTL-1 cell line, which arose from fetal liver by transformation with a retrovirus containing the Hras oncogene, Northern analysis of poly A+ mRNA as well as in situ hybridization of RNA in single cells revealed that lambda 5 and VpreB are already expressed at the progenitor stage and increase in expression as the progenitors differentiate to precursor (preB) cells, or are turned off as the progenitors differentiate to myeloid cells. Continued rearrangements of Ig genes in pre B cell lines leading to Ig expression on the surface of NFS-5 pre B cells do not influence the continued expression of VpreB and lambda 5. Surface Ig-positive B lineage cell lines also express the pre B-related genes. Both Ly1+ as well as Ly1- pre B cells are VpreB- and lambda 5 positive. Lipopolysaccharide (LPS) stimulation of 70Z/3 pre B cells does not turn off lambda 5 expression. It therefore appears that, at least in transformed cell lines, the expression of VpreB and lambda 5 is not directly regulated by the expression of microH, kappa L, or lambda L chains, LPS reactivity, or the Ly1 surface antigen. Fusion of plasmacytoma cells with normal pre B cells to generate pre B hybridomas leads to down-regulation of VpreB/lambda 5 expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419956 TI - T cell receptor alpha-chain pairing determines the specificity of residue 262 within the Kb-restricted, ovalbumin257-264 determinant. AB - Ovalbumin-specific, Kb-restricted T cells recognize the minimal fully active synthetic peptide ovalbumin (OVA)257-264. This sequence coincides with the eight residue, allele-specific peptide binding motif previously predicted from direct sequencing of naturally occurring Kb-associated peptides (Falk, K., Rotzscke, O., Stevanovic, S., Jung, G., and Rammensee, H.-G., Nature 351:290, 1990). T cell recognition of a panel of analogs with single residue substitutions between the two putative Kb anchor residues at OVA261 and OVA264 suggested that at least one residue, Glu at position 262, is involved in TCR interaction. OVA-specific cytotoxic T lymphocytes (CTL) derived from TCR beta-chain transgenic mice, where the beta-chain originates from an OVA-specific, Kb-restricted CTL B3, showed that differences in TCR alpha-chain pairing determined the specificity for OVA residue 262. These data support the notion that residue 262 of the OVA T cell determinant, corresponding to position 6 within the Kb-binding motif, represents a contact site for TCR. This residue interacts directly with the TCR alpha-chain or with a site on the TCR beta-chain whose conformation is affected by TCR alpha chain pairing. PMID- 1419958 TI - Conformational changes in mouse MHC class II proteins at acidic pH. AB - MHC class II molecules bind peptide antigens and present them to T cells. Recent evidence suggests that peptide--MHC class II interaction is regulated by pH. Both peptide binding to and dissociation from MHC class II molecules is enhanced at acidic pH. In this report we use circular dichroism to investigate the possibility that the modulation of peptide association with MHC class II molecules at acidic pH is associated with changes in MHC class II structure. Our results show that a change in the structure of the MHC class II protein A(d) occurs between pH 4 and 5, close to the pH optimum for peptide binding. More drastic changes in A(d) structure occur at lower pH levels, where peptide dissociation is enhanced. The structural changes at pH 4-5 are fully reversible upon neutralization, while changes at pH 3 are not. The pH stability of purified E(d) molecules is somewhat different, with changes observed only at pH less than 4. This may reflect a differential occupancy of the purified molecules with endogenous peptides. PMID- 1419957 TI - Properties of B cell stage specific and ubiquitous nuclear factors binding to immunoglobulin heavy chain gene switch regions. AB - The Ig heavy chain (IgH) constant region (CH) class switch is manifested by DNA deletions which exchange the C mu gene of a functional VDJ-CH rearrangement for a C gamma, C epsilon or C alpha gene. Repetitive sequences (S regions) 5' of each CH gene mediate CH gene switch recombination by an illegitimate mechanism. S mu can be subdivided into S mu 5' (non-repetitive) and S mu 3' (repetitive) components with recombination occurring in either part. Here, we describe the properties of ubiquitous and B cell stage specific S mu binding factors NFS mu-U1 and NFS mu-B1 respectively. U1 only bound to S mu 5' sequences, and B1 to S mu 5', S mu 3' sequences and to other S regions with varying affinities. DMS and OP Cu footprinting revealed the sequence AAAAAGCATGGCTGA in the U1 site while the B1 S mu 5' site overlapped the 3' end of the U1 binding site and also contained additional 3' flanking S mu repeat motifs (GAGCTGAGATGGGTGGGCT). Binding site competition assays reveal that NFS mu-B1 is either very related or identical to S alpha BP (described by Waters et al., Mol. Cell Biol. 9:5594, 1989) and BSAP (identified by Barberis et al., Genes Devl. 4:849, 1990) which were shown to bind to two sequences upstream of the S alpha repeats and within the promoters of sea urchin histone genes respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419959 TI - T cell receptor usage by HLA-DQw8-specific T cell clones. AB - To investigate whether T cells recognizing the same HLA molecule may demonstrate homology in parts of their TCR, five different HLA-DQw8-specific T lymphocyte clones (TLC) were studied. The TCR alpha and -beta genes of four alloreactive, HLA-DQw8-specific and one antigen-specific TLC were sequenced. All TLC used different V alpha and V beta genes. However, four of the TLC shared a certain CDR1 beta motif and all five used either J beta 2.3 or -2.5. In addition, two used the same J alpha. The results indicate a possible preferential usage of certain TCR structures by T cells specific for DQw8. PMID- 1419961 TI - N.m.r. study of interaction between sugar and peptide moieties in mucin-type model glycopeptides. AB - In order to investigate the structural properties of the sugar and peptide linkage region in glycoprotein, some glycopeptides were synthesized as a model for AFGP (antifreeze glycoprotein), which is one of the mucin-type glycoproteins. The results from n.m.r. measurements in DMSO and aqueous conditions revealed that the glycopeptides form an intramolecular hydrogen bond between the amide proton of N-acetylgalactosamine (GalNAc) and the carbonyl oxygen of threonine (Thr) to which the GalNAc is covalently linked. This intramolecular hydrogen bond may play an important role in determining the orientation of the sugar moiety relative to the protein backbone. The roles for the activity of the proline (Pro) residue in AFGP were also discussed. PMID- 1419960 TI - Characterization of Fc epsilon RI gamma in human natural killer cells. AB - We report the characterization of the Fc epsilon RI gamma chain which associates with the transmembrane form of CD16 to form the low affinity receptor for IgG (Fc gamma RIII) expressed on human natural killer (NK) cells. cDNA cloning and sequence analysis of Fc epsilon RI gamma from a polyclonal CD3-CD16+ NK line established that this molecule is identical to Fc epsilon RI gamma previously identified in human basophils as part of a high affinity receptor for IgE. Polymerase chain reaction analysis of Fc epsilon RI gamma gene expression in a series of CD3+CD16- and CD3-CD16+ NK clones reveals that Fc epsilon RI gamma is not directly linked to NK activity since clones of the CD3+CD16- phenotype lack Fc epsilon RI gamma RNA but nevertheless mediate cytotoxicity. Taken together, these results demonstrate that the Fc epsilon RI gamma molecule is expressed in various types within the hematopoietic system as part of multimeric surface receptors involved in different biological functions. PMID- 1419962 TI - Construction of nucleosome cores from defined DNA sequences of prokaryotic origin. AB - A procedure for the de novo construction of nucleosome core particles from defined DNA sequences of prokaryotic origin is described. Efficient de novo reconstitution without added carrier DNA is demonstrated. DNase I and exonuclease III analysis of a nucleosome core prepared from a 154 base pair fragment extending from base 853 to base 1006 of pBR322 indicates a non-random positioning of the histone core along the DNA. As bacteria have no histones, their DNA cannot be expected to have a histone core positioning signal encoded in it, the efficient formation of a uniquely positioned core particle is not self evident. The possibility that a phosphate end group positions DNA fragments on the histone is considered. The de novo reconstitution of carrier-less defined nucleosome core particles should facilitate the physicochemical study of nucleosomes on the fine structural level. PMID- 1419963 TI - Glass transition of gluten. 1: Gluten and gluten-sugar mixtures. AB - The glass transition in hydrated wheat gluten has been studied using dynamic mechanical thermal analysis, differential scanning calorimetry, pulsed nuclear magnetic resonance and a three point bend test. The results for gluten alone are in good agreement with results obtained by other workers for gluten and glutenin. In contrast to their effect on the Tg of amylopectin, a gluten:sugar ratio of 10:1 (where the sugar is amorphous fructose, sucrose or glucose) has little effect on the glass transition temperature, as a function of water content. A sample containing gluten and fructose in the ratio 2:1 showed plasticization due to the sugar. PMID- 1419964 TI - Glass transition of gluten. 2: The effect of lipids and emulsifiers. AB - The effects of lipids and emulsifiers on the glass transition temperature (Tg) of gluten have been studied as a function of water content, using differential scanning calorimetry, dynamic mechanical thermal analysis, a three point bend test and pulsed nuclear magnetic resonance. Lipids and emulsifiers were found to have little or no effect on Tg, with the exception of the lower molecular weight caproic and hydroxycaproic acids, which had a plasticizing effect. In the case of hydroxycaproic acid this was found to be in accordance with the Couchman-Karasz equation. The magnitude of the drop in modulus at Tg was increased in the presence of these additives at low water contents. The effect of lipids and emulsifiers on the Tg of gluten and their compatibility with gluten appears to depend both on their hydrophobicity and on their molecular weight. PMID- 1419965 TI - Behaviour of mouse macrophage cell line and mouse fibroblast on copolymers containing cellulose triacetate. AB - Copolymers containing cellulose triacetate were prepared under various conditions. A bacteriological plastic dish was coated with the copolymer (HCTA MDI copolymer) composed of hydrolysed cellulose triacetate (HCTA) and diphenylmethane diisocyanate (MDI). The deacetylated copolymer (DA-copolymer) was prepared by the deacetylation of HCTA-MDI copolymer. The behaviour of animal cells such as a mouse macrophage cell line (A640-BB-2 cells) and a mouse fibroblast (3T6 cells) on prepared dishes was investigated morphologically. A640 BB-2 cells showed good adhesion and smooth spreading, and 3T6 cells also showed good adhesion and sufficient cell growth on the dish coated with HCTA-MDI copolymer. These results suggest that these copolymers are useful for biomedical materials. PMID- 1419966 TI - Binding study of metal ions to S100 protein: 43Ca, 25Mg, 67Zn and 39K n.m.r. AB - The interactions of the S100 protein (S100) with metal cations such as Ca2+, Mg2+, Zn2+ and K+ were studied by the metal n.m.r. spectroscopy. The line widths of 43Ca, 25Mg, 67Zn and 39K n.m.r. markedly increased by adding all S100s. A broad 43Ca n.m.r. band of Ca(2+)-S100a solution was not affected by Zn2+ and K+, while it was greatly decreased by adding Mg2+. The 43Ca n.m.r. spectra of Ca(2+) S100a0 and -S100b solutions consisted of two slow-exchangeable signals which corresponded to Ca2+ bound to two environmentally different sites of the S100a0. These two 43Ca n.m.r. signals were not affected by Zn2+ and K+. The line width of broad 25Mg n.m.r. band of the Mg(2+)-S100 solution greatly decreased by adding Ca2+, while it did not change by adding Zn2+ and K+. Further, the addition of Ca2+, Mg2+ and K+ did not affect the line width of the 67Zn n.m.r. of the Zn(2+) S100 solutions. These findings suggest that: (1) Mg2+ binds to all S100s, and at least one of the Mg2+ binding sites of S100 molecule is the same as the Ca2+ binding site; (2) Zn2+ binds to S100s, although the binding site(s) is/are different from Ca(2+)- or Mg(2+)-binding site(s), and the environment of Zn2+ nuclei will not change even though Ca2+ binds to S100s. PMID- 1419967 TI - Gelation of globular proteins: effect of pH and ionic strength on the critical concentration for gel formation. A simple model and its application to beta lactoglobulin heat-induced gelation. AB - The influence of pH (2-9) and ionic strength (0-0.14 M NaCl) on the sol-gel transition of beta-lactoglobulin was investigated in order to determine the critical gel concentration (C0). The concentration necessary to form a gel near the isoelectric pH remains approximately constant (approximately 1% w/v) independently of the ionic strength. At other pH values, the higher the ionic strength is, the lower the protein concentration must be to form a gel. A theoretical model to relate the effect of the intensity and the range of electrostatic interactions on the critical concentration (C0) is proposed and fits reasonably with the experimental results. PMID- 1419968 TI - Control of collagen fibril diameters in tissues. AB - It is proposed that radial growth of collagen fibrils, which takes place in all connective tissues to varying extents, according to the tensile stresses exerted on them, proceeds mainly by aggregation of protofibrils (approximately 10 nm) and existing fibrils. In young tissues, fibrils are prevented from making frequent intimate contacts which would lead to aggregation by abundant interfibrillar proteoglycan, that keeps the fibrils apart. Collagen fibrils are probably unable to fuse except when the molecules within them are packed in the same sense, i.e. fusing fibrils are parallel. The roughly equal numbers of parallel and antiparallel fibrils seen in several tissues must limit radial fibril growth in older tissues, where proteoglycan is usually less abundant. Possible origins of the balance of fibril polarities, which must be conserved after fibril nucleation on cell or non-cell templates, are analysed. The two controlling factors, ambient proteoglycan and fibril polarity, working against the tendency of fibrils to fuse, account for many features of the observed distributions of collagen fibril diameters in diverse tissues and at different ages. PMID- 1419969 TI - Study on the prevention of surface-induced platelet activation by albumin coating. AB - To understand how albumin on the surface inhibits surface-induced platelet activation, we adsorbed albumin on dimethyldichlorosilane-coated glass (DDS glass) and modified the adsorbed albumin by three different methods. The adsorbed albumin was crosslinked with glutaraldehyde, dried and rehydrated, or digested with trypsin. Surface albumin concentration did not change by crosslinking; however, it decreased by about 15% by a simple dry-and-rehydration process. Trypsin digestion reduced the surface albumin concentration by 50%. Platelets were found to adhere and activate on albumin coated DDS-glass, if the adsorbed albumin was modified. The extent of platelet activation was quantified with two numeric parameters, the spread area and circularity. Fibrinogen adsorption to the dried or digested albumin layer resulted in enhancement of platelet activation, while adsorption of more albumin inhibited platelet activation. The results suggest that albumin can inhibit platelet activation as long as it covers the surface completely and remains flexible on the surface. This study indicates that steric repulsion is one of the mechanisms of surface passivation by albumin. PMID- 1419970 TI - Influence of a preadsorbed terpolymer on human platelet accumulation, fibrinogen adsorption, and ex vivo blood activation in hemodialysis hollow fibers. AB - Results are presented on kinetics of platelet accumulation in charged polyacrylonitrile (AN69) hollow fibers by continuous data recording under flow conditions (wall shear rate 108-1050 s-1), using suspensions of washed 111In labeled human platelets in Tyrode's-albumin buffer, containing washed red blood cells (0-40%). Preadsorption of a terpolymer of acrylonitrile, poly(ethyleneoxide) methacrylate and trimethylaminoethyl chloride methacrylate leads to very efficient passivation with respect to platelet accumulation and fibrinogen adsorption. In human ex vivo tests, evaluation of complement peptide C3a, platelet beta-thromboglobulin, leucocyte-polymorphonuclear neutrophile elastase and fibrinopeptide A shows no detectable activation. Furthermore, preadsorption appears to result in simultaneous improvement in hemocompatibility of the blood lines leading to and from the dialysis module. This single pretreatment of dialysis membranes should allow injection of lower doses of anticoagulant to patients submitted to hemodialysis. PMID- 1419971 TI - Growth of uropathogenic Escherichia coli strains at solid surfaces. AB - The adhesion and growth of two catheter-associated (O2K2 and O83K?) and two non catheter-associated (O111K58 and O157K-) uropathogenic Escherichia coli strains on glass, poly(methyl methacrylate) (PMMA), a negatively charged copolymer of MMA and methacrylic acid (MAA) and a positively charged copolymer of MMA and trimethylaminoethyl methacrylate chloride (TMAEMA-Cl) were studied. The solid surfaces were placed in a parallel plate perfusion system. After preadhesion of the bacteria onto the surfaces, growth was initiated by perfusing the system with MacConkey broth. Growth was measured by counting adherent bacteria as a function of time. Bacterial strains were characterized by means of water contact angle, microbial adhesion to hydrocarbon (MATH), anion exchange resin retention (ARR) and zeta potential measurements. Solid surfaces were characterized by means of water contact angle and zeta potential measurements. The catheter-associated strains had significantly higher water contact angles, zeta potentials and ARR values than the non catheter-associated strains. Non catheter-associated strains did not grow at the surfaces used. Catheter-associated strains did not grow at the positively charged surface but exhibited growth at the other surfaces. Strains grew more rapidly at surfaces with a relatively high negative zeta potential and a low water contact angle than at surfaces with a relatively low negative zeta potential and a high water contact angle. The growth of strain O2K2 on glass was significantly reduced when urine instead of MacConkey broth was used as perfusion medium. PMID- 1419972 TI - A new apheresis system using a copolymer (polyvinyl alcohol triethylene glycol diacrylate) for removal of LDL from dog whole blood. AB - Studies were undertaken to determine the effectiveness of a copolymer composed of PVA-TEGDA (Poly Vinyl Alcohol TriEthylene Glycol) as a plasma-cholesterol lowering procedure. For a comparative study, five dogs underwent plasmapheresis including the transfusion bag containing gel in the plasma line, while three control dogs underwent the same plasmapheresis without gel. Numerous biological determinations were performed firstly in whole blood circulation before and after treatment over 10 days, and secondly in plasma before and after LDL binding on the gel. In the whole blood circulation, the average significant depletion of cholesterol levels was 31-51% for treated, 0-16% for control dogs and the average significant depletion of LDL cholesterol was 26-75% for treated and 0-3% for control dogs. Gel was therefore able to bind 121-217 mg of total cholesterol and 34-70 mg of LDL cholesterol per gram of gel. Lipid and lipoprotein levels rebounded 3-4 days after treatment. Adverse effects were not observed during all plasmapheresis. No significant differences between control plasmapheresis and gel plasmapheresis were obtained for blood cell counts while lengthened coagulation times were observed during 24 h. Complement was not significantly activated by the copolymer as shown by a same decreased activity in the blood stream of all dogs: in fact, CH 50 depletion in the gel incubated plasma was due to a protein adsorption on the hydrogel. This new approach for LDL apheresis appears to be a promising new technique. PMID- 1419973 TI - The effect of an intramedullary self-reinforced poly-L-lactide (SR-PLLA) implant on growing bone with special reference to fixation properties. An experimental study on growing rabbits. AB - Polylactic acid (PLA) is a synthetic biodegradable material. The self-reinforced implants made of poly-L-lactic acid (SR-PLLA) were manufactured of biodegradable polymeric matrix reinforced with fibres of the same material. The purpose of this study was to find out the effect of an intramedullary SR-PLLA implant on growing bone and its applicability to the fixation of a femoral shaft osteotomy in a growing rabbit. In seven rabbits 6 weeks of age a SR-PLLA implant 2.0 mm in diameter and 50 mm in length was introduced into the intramedullary cavity of the right femur. A proximal femoral shaft osteotomy of the right femur was made in another ten 6-weeks-old rabbits. After accurate reduction, fixation of the osteotomy was achieved with an intramedullary 2.0 mm by 50 mm SR-PLLA-rod. The follow-up times were 6 and 28 weeks. An intramedullary SR-PLLA-rod neither caused any disturbance of the bone growth nor abnormalities of the peripheral blood cell counts. Solid union of the osteotomy was seen in six weeks after fixation with SR PLLA implant. PMID- 1419974 TI - A new hydrophilic polymer for biomaterial coatings with low protein adsorption. AB - BIOPOL polyurethane polymers, an extension of the HYPOL Polymer series of foamable hydrophilic polymers, have been developed which exhibit improved performance for selected biomedical applications. Members of the BIOPOL polyurethane polymer series, with molecular weights in the range of 7000 to 30,000, are larger molecules than HYPOL polymers (MW less than 3000) and produce hydrogels, rather than foams, when mixed with water. The prototype material in this series, BIOPOL XP-5, is a liquid prepolymer which chain extends in water and forms a hydrogel which can contain greater than 85% water. The time required for polymerization with water was dependent on the prepolymer: water ratio. This prepolymer was coated onto silica and medical grade tubing and then cured in place with water to form a stable coating which was resistant to non-specific protein binding. In addition, soluble, isocyanate-free forms of the prepolymer were tested for toxicity and shown to produce no adverse effects when injected intravenously into mice or when applied to a chicken chorioallantoic membrane. BIOPOL polymers can be useful in applications where protein adsorption is an undesirable event. PMID- 1419976 TI - In vitro cytotoxicity of melanized poly(2-hydroxyethyl methacrylate) hydrogels, a novel class of ocular biomaterials. AB - Due to their ability to absorb ultraviolet and visible radiation, we have proposed the melanized poly(2-hydroxyethyl methacrylate) hydrogels as biomaterials suitable for the manufacture of soft artificial intraocular lenses. Their biocompatibility has not been evaluated so far. In this study, poly(2 hydroxyethyl methacrylate) containing various amounts of adrenochrome-melanin were synthesized and the cytotoxicity of their aqueous extracts was assessed by using four in vitro testing techniques (trypan blue dye exclusion, inhibition of DNA synthesis, lactate dehydrogenase release, and inhibition of cell growth). Assays were based on incubation with human choroidal fibroblasts. By the first three techniques, no cytotoxicity was found in the extracts. The inhibition of cell growth test showed a slight cellular protein loss, however only in the extracts of polymers with high melanin content. The results suggest that the release of potentially toxic agents from melanized hydrogels into an aqueous medium is not significant. However, when an assay in collagen gel was carried out in the presence of specimens of melanized hydrogels, a toxic reaction was clearly revealed. This can be caused by a delayed release of toxic molecules from melanin, or by some other mechanism. The use of melanin-containing polymers as implant materials becomes questionable and further research is necessary. PMID- 1419975 TI - Surface characterization of 2-hydroxyethyl methacrylate/styrene copolymers by angle-dependent X-ray photoelectron spectroscopy and static secondary ion mass spectrometry. AB - The surface composition and structure of three structurally distinct amphiphilic copolymers of 2-hydroxyethyl methacrylate (HEMA) and styrene have been examined with angle-dependent X-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectrometry (SIMS). The phase-separated block copolymer made by anionic living polymerization, HSH-A50, showed significant surface enrichment of styrene. The outermost 2-3 A appeared to be approximately 100% styrene, with the styrene concentration decreasing to its bulk value at a depth of approximately 50 A from the surface. However, HEMA was detected in the outer 20 A of this copolymer. The presence of HEMA in the surface region implies this copolymer may undergo significant restructuring when hydrated in a hydrophilic environment (as opposed to the hydrophobic environment in which the sample was prepared and analyzed). The phase-separated block copolymer made by telechelic coupling of free radical polymerized functionalized oligomers, HSH-B60, showed only slight styrene enrichment at the surface. Both HEMA and styrene were detected at all sampling depths, including the outermost surface layer, consistent with the presence of discrete HEMA and styrene domains at the copolymer surface. Since both components are already present at the surface under hydrophobic conditions, the degree of restructuring this copolymer may undergo upon hydration should be minor. The random HEMA--styrene copolymer made by conventional free radical initiation techniques, HS-RAN50, had a surface composition that was similar to the bulk composition and independent of depth, as expected for a homogeneously mixed copolymer film. PMID- 1419977 TI - Control of adhesion and detachment of parenchymal liver cells using lactose carrying polystyrene as substratum. AB - Adhesion of hepatocytes on culture dishes whose surface was coated with a lactose carrying styrene homopolymer (PVLA) was investigated. Hepatocytes maintained their round shape on PVLA substratum, which is in contrast to the usual spread shape characteristic of those cultured on collagen and fibronectin substrata. Calcium ion was indispensable for hepatocyte adhesion in PVLA substratum, and hence the hepatocytes on PVLA were easily detached when the culture was treated with ethylenediamine tetraacetic acid (EDTA). The recovered hepatocytes readheres to PVLA. The adhesion of hepatocytes to PVLA was not inhibited by cytochalasin B but by colchicine. Hepatocytes recognize the galactose moieties on the surface of asialoglycoproteins and removes these proteins from the blood stream by receptor mediated endocytosis. The mechanism of adhesion of hepatocytes on PVLA substratum which contains a high density of galactose residues was distinct from the attachment on collagen and fibronectin substrata, and showed great similarity to the receptor and ligand interactions which occurs in the clearance of asialoglycoproteins by hepatocytes. PMID- 1419978 TI - Cytocompatibility study of NHLBI primary reference materials using human endothelial cells. AB - Four different materials, low density polyethylene (LDPE), polydimethylsiloxane (PDMS), polyvinylcholoride (PVC) and cellulose, were selected by the Devices and Technology Branch of the National Heart Lung and Blood Institute (NHLBI) as primary reference materials for blood contacting. Among the wide variety of tests proposed to assess hemocompatibility of short-term blood contacting catheters, it was desirable to rule out whether these materials could release toxics for vascular cells of the physiological environment. Thus, the cytocompatibility of these materials have been checked towards human umbilical vein endothelial cells: the method used avoids direct contact between cells and materials but evaluates the effect of possible toxic substances leached from materials. These substances were obtained under defined conditions according to a standard. The results show that the extracts of cellulose and LDPE provoke an important cytotoxic effect on the endothelial cell cultures, while the extracts of PDMS and PVC allow the obtention of endothelial cell lining of the reference surface, with a correct global metabolic activity and the intracellular presence of von Willebrand factor. PMID- 1419979 TI - Some methods for evaluating clinical itch and their application for studying pathophysiological mechanisms. AB - Research on itch has been hampered by difficulties in measuring the itch sensation. A microcomputer-based system, where the patients themselves record their symptoms on portable data loggers can be used for quantitative measurements of clinical itch and for the detection of antipruritic effects of drugs. By using this system we have found that itch in atopic dermatitis is not inhibited by antihistamines but by cyclosporin A, a drug inhibiting cytokine production. Thus histamine is not a major pruritogen in atopic dermatitis. A hypothesis is proposed that cytokines are involved in itch in atopic dermatitis. PMID- 1419980 TI - Localization of fibronectin in the initial lymphatics and blood vessels of normal human skin: an immunoelectron microscopic investigation. AB - The initial lymphatics of the human skin do not possess a basal lamina, but a subendothelial fibrous network, of which we do not know the biochemical and immunohistological composition. We investigated the wall of blood vessels and initial lymphatics in normal human skin for the presence of fibronectin by immunoelectron microscopy. We found discontinuous linear subendothelial diaminobenzidine (DAB) reaction products in both blood vessels and lymphatics. In addition fibronectin could be found at the anchoring fibrils of the initial lymphatics. PMID- 1419981 TI - Immunohistological analysis of P53 expression in human skin tumors. AB - The p53 expression in various skin tumors was immunohistologically evaluated using two mouse monoclonal anti-p53 antibodies, PAb421 and PAb1801. The p53 expression was not detected in the normal epidermal cells. Nuclear staining suggested that the p53 expression was observed in 10 of 26 squamous cell carcinomas (SCCs) from 24 patients, in one undifferentiated carcinoma, one proliferating trichilemmal cyst, one malignant proliferating trichilemmal tumor and in one metastatic carcinoma of breast cancer. None off four cases of Bowen's disease (SCC in situ) showed nuclear staining. In the SCCs, five of 20 primary lesions, three of four recurrent lesions and both of two metastatic lesions had positive nuclei. There was one case of SCC in which a primary lesion was negative but a recurrent lesion was positive. Thus, p53 expression was more frequently observed in SCCs at more clinically advanced stages. This may suggest that p53 has some relevance to progression of SCC. Nuclear staining was not detected in any of the following cases: two cases of seborrheic keratosis, one eccrine poroma, one keratoacanthoma, 11 basal cell epitheliomas, two mammary Paget's disease, three genital Paget's disease, one sebaceous carcinoma, four malignant melanomas, six lymphomas, two leukemia cutis and two angiosarcomas. PMID- 1419983 TI - Association of ras p21 with differentiation of epidermal keratinocytes in proliferating skin diseases. AB - We examined the localization of DNA replicating cells and ras oncogene product p21 positive cells in proliferating skin diseases, such as psoriasis vulgaris, lichen planus, verruca vulgaris, verruca plana juvenilis and seborrheic keratosis. ras p21-positive cells were found rather in the differentiated layers than in the proliferating layers of the epidermis. We indicate that the expression of ras p21 can be associated with the differentiation of epidermal keratinocytes not only in tumor tissues but also in inflammatory skin disease. PMID- 1419982 TI - Differences in HTLV-I integration patterns between skin lesions and peripheral blood lymphocytes of HTLV-I seropositive patients with cutaneous lymphoproliferative disorders. AB - We examined HTLV-I integration patterns in nine cases of HTLV-I-seropositive patients with cutaneous lymphoproliferative disorders. The Southern blot on EcoRI digests of DNA revealed a discrete band of HTLV-I provirus (monoclonal integration) in either skin lesions or peripheral blood lymphocytes (PBL). Four cases showed the monoclonal integration of HTLV-I provirus only in skin lesions: one case showed only in PBL and two cases showed in both skin and PBL. The Southern blot on PstI digests of DNA revealed a 2.4 Kb band of the internal construct of HTLV-I provirus (polyclonal integration) in the PBL of EcoRI negative samples. The difference in HTLV-I integration patterns between skin lesions and PBL in these cases suggests that the monoclonal outgrowth of HTLV-I infected cells in the skin is causatively associated with the pathogenesis of cutaneous ATL. PMID- 1419984 TI - Role of fibronectin in the adherence of Staphylococcus aureus to dermal tissues. AB - Staphylococcus aureus has a fibronectin receptor on its surface. Fibronectin seems to play a role in the initiation and modification of infection with S. aureus. We studied the role of fibronectin in the binding of S. aureus (clinical isolates) to dermal tissues in mice, and the relationship between the fibronectin binding ability of S. aureus and clinical features of S. aureus skin infections. Mice were inoculated with S. aureus incubated with gold-particles bound fibronectin and skin specimens were taken for electron microscopic examination. The number of gold particles surrounding the S. aureus cells decreased with time, with none detected 4 h after inoculation. At both 5 min and 1 h after inoculation, gold particles were only found on the free surface of S. aureus cells and not in the interface between S. aureus cells and fibroblasts. Fibronectin-bound gold particles were bound more extensively to S. aureus strains isolated from furunculosis or furuncle than to those from bullous impetigo. These results suggest that the matrix fibronectin on the surface of the fibroblasts of mice contributes to the adherence of S. aureus to the fibroblasts, and that the number of fibronectin binding sites on S. aureus cells is related to the degree of local invasiveness. PMID- 1419985 TI - Decompensation in proteinase-inhibitor system and application of proteinase inhibitors in pemphigus and pemphigoid. AB - The goal of this study was to determine levels of serine proteinases and their inhibitors in serum and blister fluid of patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP) in the course of treatment with prednisolone and proteinase inhibitors such as Contrycal and epsilon-aminocaproic acid. Assessment of the total proteolytic activity of serine proteinases (TPASP) and total antitryptic activity (TATA) is sera and blister fluids from 53 PV and 38 BP patients showed abnormalities in the proteinase and proteinase inhibitor levels in the acute stage of these bullous dermatoses. In PV, the level of TRASP was raised to 495 +/- 73 mU/ml (control 246 +/- 48 mU/ml; P < 0.001) in serum and to 849 +/- 96 mU/ml (control 189 +/- 34 mU/ml; P < 0.001) in blister fluid. In BP, the level of TRASP was raised to 472 +/- 101 mU/ml (P < 0.001) and 796 +/- 103 mU/ml (P < 0.001) in serum and blister fluid, respectively. In both dermatoses, the increase in serine proteinase activity developed against the background of decreased or unchanged antiproteolytic activity. TATA levels dropped to 16 +/- 5 inhibitory units (iU)/ml (control 26 +/- 5 iU/ml; P < 0.001) in PV serum and to 6 +/- 1 iU/ml (control 20 +/- 2 iU/ml: P < 0.001) in PV blister fluid. In BP, serum TATA levels were within normal values, whereas blister fluid TATA levels were significantly decreased (14 +/- 3 iU/ml; P < 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1419986 TI - Sebaceous gland activity and urinary androgen levels in children. AB - Sebum and 24-h urine samples were collected from 17 children, aged 10-17 years. Wax ester (WE) secretion rates were measured as the index for sebaceous gland activity. The fatty acid methyl esters were analyzed by capillary gas chromatography. Urinary testosterone as well as 17-ketosteroids (androsterone, dehydroepiandrosterone (DHEA), and etiocholanolone) were separated from the urine samples and analyzed by gas chromatography. WE secretion rates increased with age and there were correlated changes in the monounsaturated fatty acids of WEs. Straight chain types such as 14:1 and 16:1 tended to increase, while 18:1 tended to decrease. There was a negative correlation between iso even fatty acids and WE secretion rates. However the other chain types such as straight odd, iso odd and anteiso odd showed no statistically significant change in relation to WE secretion rates. WE secretion rates were correlated positively with testosterone levels in both sexes, with DHEA in males, and with etiocholanolone in females. The results suggest that sebaceous gland activity is stimulated by adrenocortical androgens in prepuberty, in addition to the strong effect of testosterone during puberty. PMID- 1419987 TI - Intrauterine rhythm and blues? PMID- 1419988 TI - Antibiotic prophylaxis and caesarean section. PMID- 1419989 TI - Antenatal cardiotocogram quality and interpretation using computers. AB - OBJECTIVE: To test the application in practice of computerized fetal heart rate (FHR) analysis in pregnancy. DESIGN: Randomized distribution of subjects with computerized analysis automatically revealed or concealed. SETTING: A district general hospital and a teaching hospital outside London. SUBJECTS: 2869 pregnant women studied within a year. OUTCOME MEASURES: Quality and duration of the cardiotocogram; quantitative measurement of FHR variation; number of stillbirths. RESULTS: With interactive advice to the operator, records were of improved quality (up to 28% without signal loss) with potentially much reduced recording time. The short-term FHR variation measured in the last records before intervention is reported for the first time. CONCLUSION: The benefits of using the computers include improvement in record quality and saving of time. In addition, where interpretation depended on estimation of FHR variation there was prima facie evidence of observer misinterpretation; visual analysis was unreliable. A larger trial is now required with more rigorous constraints on intervention. PMID- 1419990 TI - Previous miscarriage and stillbirth as risk factors for other unfavourable outcomes in the next pregnancy. AB - OBJECTIVE: To look for associations between previous fetal loss and fetal malformation or low birthweight in a subsequent pregnancy. DESIGN: A case-control study with place of birth, time and sex matched controls. SETTING: 72 South American maternity hospitals. SUBJECTS: 18,534 malformed, 1150 non-malformed babies of low birthweight and 16,394 controls. All babies were from mothers with at least one previous pregnancy. MAIN OUTCOME MEASURES: Frequency of stillbirths and miscarriages in the previous pregnancy and outcome of the index pregnancy. RESULTS: Multiple malformation, Down's syndrome, anencephaly, spina bifida, pes equinovarus, congenital dislocation of the hip and low birthweight are associated with previous fetal loss. CONCLUSION: A miscarriage or a stillbirth in a previous pregnancy should be taken into account when the risk of malformations or low birthweight in a subsequent pregnancy is assessed. PMID- 1419991 TI - Lack of relation between fetal blood gases and fetal blood flow velocity waveform indices found in rhesus isoimmunised pregnancies. AB - OBJECTIVE: To investigate the relation between umbilical vein blood gas components and the vascular resistance in four fetal arteries in Rh-immunised pregnancies. DESIGN: A prospective observational study over a 4-month period. SETTING: King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. SUBJECTS: Fifteen Rh-isoimmunised pregnant women. INTERVENTIONS: Pulsed Doppler examinations of the umbilical artery, fetal internal carotid artery, thoracic aorta and abdominal aorta before transabdominal fetal blood sampling from the umbilical vein on 38 occasions. MAIN OUTCOME MEASURES: Doppler flow velocity pulsatility index (PI), systolic/diastolic ratio (A/B) and resistance index (RI) in the four fetal arteries investigated were related to the umbilical vein blood gases and acid-base status (PO2, PCO2, O2-content, CO2-content, HCO3, base excess and lactate concentration). RESULTS: There were no correlations between the Doppler indices in any of the vessels studied and the blood gases components in the umbilical vein. The ratios between the corresponding Doppler indices in the different vessels were also independent of the blood gases and acid-base status and there were no significant differences in the Doppler indices in the same vessel between fetuses with blood gas values over the 75th centile and those with values below the 25th centile. CONCLUSION: This study does not support a reduction in peripheral vascular resistance in the fetal cerebrum in relation to fetal hypoxia in Rh-immunized pregnancies. PMID- 1419992 TI - A comparison between computerised (mean range) and clinical visual cardiotocographic assessment. AB - OBJECTIVE: To compare computer cardiotocographic (CTG) analysis with clinical visual analysis. DESIGN: A retrospective blind comparison of the two techniques of CTG assessment. SETTING: Fetal Assessment Unit, King's College Hospital, London. SUBJECTS: One hundred CTG traces of women referred to the unit were studied; the traces were taken after 32 weeks' gestation, within 10 days of delivery and where outcome was known. INTERVENTIONS: The CTG traces were assessed both by the computer (System 8000 computerised CTG analyser, Oxford Sonicaid Ltd) and visually, by one of us. MAIN OUTCOME: Computer mean range from 0 to 80 in ms clinical visual CTG score from 0 to 80 (arbitrary units). A score < 20 is ominous; suspicious when between 20 and 30; and normal when > 30. RESULTS: There was close correlation between the computer mean range and clinical visual assessment (r = 0.78, n = 100, P = 0.001). However, there were 13 occasions where the computer classified the trace as abnormal when clinical visual assessment was normal, indicating computer false positives. All these pregnancies had normal outcomes. There were no traces where computer analysis was normal and clinical visual assessment abnormal. CONCLUSIONS: Computerised CTG analysis gives an objective assessment which agrees closely with experienced visual assessment. It also provides a number which can be used to assess the value of fetal heart rate analysis. PMID- 1419993 TI - The risk of acute myocardial infarction after oestrogen and oestrogen-progestogen replacement. AB - OBJECTIVE: To determine the relative risk of developing a first acute myocardial infarction after treatment with oestrogens alone or oestrogen-progestogen combinations. DESIGN: Prospective cohort study utilizing a prescription-based and record linkage system for a follow-up period from 1977 to 1983. Average individual observation time was 5.8 years. SETTING: The entire female population of the Uppsala Health Care Region (1.4 million inhabitants), one-sixth of the total Swedish population. SUBJECTS: 23,174 women aged 35 years and older, identified from pharmacy records as having been prescribed non-contraceptive oestrogens during 1977-1980. OUTCOMES: Admissions to hospitals for first acute myocardial infarctions. RESULTS: Overall, 227 cases of a first acute myocardial infarction were observed as against 281:1 expected, RR = 0.81 (95% confidence limits 0.71 to 0.92). Women who were younger than 60 years at entry into the study and prescribed oestradiol compounds (1-2 mg) or conjugated oestrogens (0.625-1.25 mg) showed a significant 30% reduction of the relative risk (RR = 0.69, 0.54 to 0.86). Those prescribed a combined oestradiol-levonorgestrel brand also demonstrated a significantly lowered relative risk (RR = 0.53, 0.30 to 0.87). The risk estimates were near unity during the first year of follow-up but decreased during subsequent years. Exposure to the weak oestrogen oestriol did not alter the risk. CONCLUSION: Hormonal replacement therapy with oestrogens alone, and maybe also when cyclically combined with progestogens, can reduce the risk of acute myocardial infarction. PMID- 1419994 TI - Outpatient falloposcopy: intra-luminal imaging of the fallopian tube by trans uterine fibre-optic endoscopy as an outpatient procedure. AB - OBJECTIVE: To develop trans-uterine falloposcopy using the linear eversion technique in outpatients. DESIGN: A prospective, descriptive study of the introduction and application of this new technique. SETTING: A tertiary referral University Research Clinic independent of operating theatres and inpatient admission. SUBJECTS: Twenty-one infertile women with previous evidence of fallopian tube disease. MAIN OUTCOME MEASURES: Rate of successful tubal cannulation and procedure completion, tubal section visualized, condition of the tubal epithelium, subsequent treatment plan. RESULTS: A bilateral examination was attempted in 19/21 patients and completed in 18. Two early falloposcopies with inadequate analgesia were aborted due to pain after only one tube had been examined without an attempt to identify or cannulate the contralateral tubal ostium. In one patient, neither ostium was identified or cannulated. After ostial localization, 37/37 tubes were cannulated. If the ostium was not localized but 'blind' cannulation attempted, 1/3 were cannulated successfully. Epithelium characteristic of the ampulla was seen in 31/38 (82%) tubes, and of the proximal tube only in 3/38 (8%). Successful bilateral assessment noted complete bilateral proximal obstruction in 2/18 patients, non-obstructive bilateral endotubal damage in 7/18, unilateral damage in 3/18 and bilateral healthy tubes in 6/18. Unilateral examination in two patients found minimal evidence of damage in one and severe intra-tubal adhesions in the other. After falloposcopy, 11/21 patients elected for IVF, 9/21 tubal surgery and 1/21 for IVF whilst awaiting surgery. CONCLUSION: Falloposcopy is a technique which can be performed in an outpatient clinic. It is well tolerated, and high rates of luminal cannulation and visualization are possible. Atraumatic access to the tube and visualization of its lumen offer exciting opportunities for diagnosis and treatment of tubal conditions. PMID- 1419995 TI - Intergenerational studies of human birthweight from the 1958 birth cohort. II. Do parents who were twins have babies as heavy as those born to singletons? AB - OBJECTIVE: To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants. DESIGN AND SUBJECTS: The association between the birthweight of singleton parents and their offspring and that between twin parents and their offspring was compared using data from the 23-year-old sample of the 1958 British national birth cohort. The numbers available for full comparison were 1027 female and 611 male singleton cohort members, and 26 female and 17 male twin cohort members and their first singleton livebirths. RESULTS: Of the mothers who had been twins, half had been of low birthweight, and overall their mean weight was 700 g less than that of their singleton counterparts. Nevertheless, the mean birthweight of babies of twin mothers was 133 g, and of twin fathers 94 g, greater than of babies of corresponding singletons. For female, but not male, parents this difference persisted after adjustment for confounding variables. CONCLUSIONS: We suggest two possible reasons for the difference between the weight of babies of twin and singleton mothers. Firstly, the growth of twins becomes retarded late in pregnancy, possibly after a period critical in determining long-term reproductive effects. Secondly, the twin survivors were of higher birthweight than the original twin cohort, whilst the singleton survivors were more representative of all singleton births, thus introducing a possible bias. PMID- 1419996 TI - A prospective study comparing the outcome of oocytes retrieved in the aspirate with those retrieved in the flush during transvaginal ultrasound directed oocyte recovery for in-vitro fertilization. AB - OBJECTIVE: To study prospectively the fate of oocytes collected from the follicular aspirate and subsequent flushes during transvaginal ultrasound directed oocyte recovery for in-vitro fertilization (IVF). SETTING: A tertiary referral assisted conception centre. SUBJECTS: 100 consecutive patients undergoing 100 cycles of IVF. Four patients were withdrawn because their embryos were electively cryopreserved. Therefore 96 cycles were studied. MAIN OUTCOME MEASURES: The oocyte recovery rate, viability, fertilization and cleavage rates and outcome of embryos generated from oocytes that were obtained from either the initial aspirate (A1), dead space in the collecting system (A2) or the first two 2 ml flushes (F1 and F2) were compared. RESULTS: The overall oocyte recovery rate was 87.8%. Of the 1046 oocytes collected, 40.3% were from A1, 41.3% from A2, 13.7% from F1 and 4.7% from F2. There were comparable numbers of viable and fertilized oocytes and cleaved, transferred and frozen embryos in tubes A1 and A2 but all these parameters were significantly lower in tubes F1 and F2 (P < 0.0001). All these parameters were also significantly higher in F1 compared with F2 (P < 0.001), except for the number of embryos frozen, in which there was no difference. The overall pregnancy rate per cycle was 28.1% and the pregnancy rate per embryo transfer was 31.0%. There were no pregnancies in any of the cycles in which embryos originating from F2 were transferred, nor were there pregnancies in cycles in which only embryos from F1 were transferred. CONCLUSION: Follicular aspiration together with one 2 ml flush maximises the recovery of oocytes that will result in pregnancies. PMID- 1419997 TI - Maternal and fetal atrial natriuretic peptide levels at delivery from normal and growth retarded pregnancies. AB - OBJECTIVE: To determine whether circulating fetal levels of the vasodilator atrial natriuretic peptide (ANP) are reduced in pregnancies complicated by intrauterine growth retardation (IUGR). DESIGN: Prospective observational study. SETTING: University teaching hospital and research laboratory. SUBJECTS: 25 normal singleton pregnancies delivered at term by spontaneous vertex delivery (n = 16) or by elective caesarean section (n = 9), and a series of 14 singleton pregnancies complicated by IUGR. INTERVENTION: Measurement of ANP by radio immunoassay in maternal venous, umbilical artery, and umbilical vein plasma from a series of normal, and IUGR pregnancies. MAIN OUTCOME MEASURES: Comparison of plasma ANP levels between the three groups; relation between fetal ANP, PO2 and pH. RESULTS: Mode of delivery did not influence either maternal, umbilical artery or umbilical vein plasma ANP levels in normal term singleton pregnancies. Umbilical vein ANP levels were significantly higher in the IUGR group when compared with normal pregnancies at term (mean 66 95%, CI 36-122 vs mean 37, 95% CI 29-47 pg/ml, P = 0.03) and were inversely related to umbilical artery pH (R2 = 65%; P = 0.003). CONCLUSIONS: These data suggest that umbilical vein ANP levels are elevated in pregnancies complicated by IUGR, and rise appropriately in response to the stress of acidosis. In the absence of any receptor or second messenger defect within feto-placental vascular smooth muscle, these data suggest that ANP is not directly implicated in the vascular pathophysiology of IUGR. PMID- 1419998 TI - Raynaud's phenomenon and peripheral gangrene complicating scleroderma in pregnancy--diagnosis and management. PMID- 1419999 TI - Magnetic resonance imaging pelvimetry: a useful adjunct in the management of the obese patient. PMID- 1420000 TI - Recurrent idiopathic non-immunologic hydrops fetalis: a report of two families, with three and two affected siblings. PMID- 1420001 TI - Unreactive fetal heart rate pattern and atrial flutter. PMID- 1420002 TI - Determination of twin zygosity by DNA hybridisation to wild type bacteriophage M13. PMID- 1420003 TI - Measurement of amniotic fluid volume in early labour is a useful admission test. PMID- 1420004 TI - Can out-of-hours work by junior doctors in obstetrics be reduced? and role of senior house officer in the labour ward. PMID- 1420005 TI - Role of prostaglandins in the management of prelabour rupture of membranes at term. PMID- 1420006 TI - WHO appropriate technology for birth revisited. PMID- 1420007 TI - A case-control study of unexplained antepartum stillbirths. AB - OBJECTIVE: To ascertain factors that will identify women who are at increased risk of unexplained antepartum stillbirth. DESIGN: Matched case-control study. The cases and controls were initially analysed as a whole group and again after dichotomizing into those of low birthweight (< 2500 g) and those of normal birthweight (> or = 2500 g). SETTING: Western Australia 1980-1983. SUBJECTS: Unexplained antepartum stillbirths of > or = 1000 g birthweight (cases) and liveborn infants individually matched for year of birth, plurality, sex and birthweight of infant and race of mother (controls). RESULTS: The case pregnancies had more polyhydramnios (OR 10.83, 95% CI 2.41-48.69) and cord problems (OR 6.57 95% CI 1.36-31.75) than the controls but, paradoxically, other obstetric and medical complications were less common in the cases. The association with polyhydramnios persisted when the analysis was confined to those with low birthweight. With normal birthweight fetal distress was more frequent in the cases (OR 3.65 95% CI 1.36-9.80) but there were few other differences. CONCLUSIONS: The clinical and diagnostic systems currently in use are unable to identify many fetuses at risk of death. Decreases in the rate of unexplained antepartum stillbirths await the discovery of new preventable causes, or of innovations in clinical or laboratory aspects of obstetric care. PMID- 1420008 TI - A case-control study of intrapartum stillbirths. AB - OBJECTIVE: To determine antenatal and intrapartum risk factors for intrapartum stillbirths in a total population. DESIGN: Matched case-control study. SETTING: Western Australia 1980-1983. SUBJECTS: Intrapartum stillbirths of > or = 1000 g birthweight (cases) and liveborn infants (controls) individually matched for year of birth, plurality, sex and birthweight of infant and race of mother. RESULTS: Intrapartum stillbirths were more likely than controls to have had placental abruption (OR = 9.55, CI = 2.09-43.69), fetal distress (OR = 4.64, CI = 1.92 11.19), cord prolapse (OR = 10.00, CI = 1.17-85.60) and unhealthy placentas (OR = 2.26, CI = 1.13-4.52), and more likely to have been born by vaginal breech manoeuvre (OR = 3.51, CI = 1.40-8.80) and emergency caesarean section (OR = 2.15, CI = 1.13-4.10); mothers of intrapartum stillbirths were less likely to have had no labour (OR = 0.14, CI = 0.04-0.55) and to have been delivered normally (OR = 0.20, CI = 0.10-0.40). Mothers of cases born by emergency caesarean section had longer labours than mothers of controls born by this method. All intrapartum stillbirths with breech presentation were born by vaginal breech manoeuvre compared with only 53% of the controls; the remainder of the controls were born by caesarean section. CONCLUSIONS: Results indicate that little could have been done early in pregnancy to prevent the intrapartum stillbirths as no antenatal risk factors predicted these deaths. Most of the risk factors identified related to labour and delivery problems. Considering cases born by emergency caesarean section, delivery of the mother earlier in labour may have prevented some of the deaths. PMID- 1420009 TI - Risks of anal incontinence from subsequent vaginal delivery after a complete obstetric anal sphincter tear. AB - OBJECTIVE: To assess the influence of various risk factors on long term anal incontinence in women with a complete obstetric tear of the anal sphincter. DESIGN: Postal questionnaire. SETTING: Department of Gynecology and Obstetrics, Aarhus University Hospital, Denmark. SUBJECTS: 152 women with complete obstetric tear of the anal sphincter. MAIN OUTCOME MEASURES: Occurrence and duration of anal incontinence in relation to any delivery. RESULTS: 56 of 121 respondents had experienced a subsequent vaginal delivery; 23 (41%) of these had had transient anorectal incontinence directly after the complete tear and four (7%) had permanent anorectal incontinence. In the 23 women with transient anorectal incontinence directly after the complete tear, 9 (39%; 95% CI 19%-59%) developed anorectal incontinence after the next delivery, and this was permanent in four (17.4%; 95% CI 2%-33%). In the 29 women without anorectal incontinence after complete tear, two had transient incontinence of flatus but for less than 14 days after the next delivery. CONCLUSIONS: Transient anal incontinence after a complete tear is a predictor of anal incontinence after subsequent vaginal delivery. The major long term problem in our study of premenopausal women was incontinence of flatus. This possibility should be discussed with the women when a further pregnancy is planned. PMID- 1420011 TI - Determinants of pregnancy heartburn. AB - OBJECTIVE: To study the prevalence and severity of reflux symptoms in pregnancy. DESIGN: Self-administered questionnaire detailing age, race, gestational age, parity, weight, height, symptoms and severity of gastro-oesophageal reflux. SETTING: An antenatal clinic in a teaching hospital. SUBJECTS: 607 consecutive women at various stages of pregnancy were recruited during attendance at antenatal clinic. RESULTS: The prevalence of heartburn increased with gestational age (22% in the first, 39% in the second, and 72% in the third trimester; P < 0.0001), as did severity of heartburn (P < 0.0001). Pharyngeal regurgitation as a symptom showed little increase during advancing pregnancy. Symptoms of heartburn rapidly increased towards the end of the second trimester. The decrease in heartburn traditionally expected during the last three weeks of pregnancy (fetal head descent) was not observed. Logistic regression analysis showed increased risk of suffering heartburn with increasing gestational age (P < 0.0001), pre pregnancy heartburn (P < 0.0001), parity (P < 0.0001) and inversely with maternal age (P < 0.05) but not with body mass index before pregnancy, race, or weight gain in pregnancy. CONCLUSION: Heartburn, but less so pharyngeal regurgitation, increases in prevalence and severity with gestational age and parity. We speculate that hormone-related impairment of distal oesophageal clearance mechanisms may have a crucial bearing on whether heartburn develops in those individuals at greatest risk. PMID- 1420012 TI - Do fetal pulse oximetry readings at delivery correlate with cord blood oxygenation and acidaemia? AB - OBJECTIVE: To assess the accuracy of a pulse oximeter in the fetus. DESIGN: A prospective descriptive study, comparing oxygenation and acidaemia of cord blood with oxygen saturation in the arteries of the fetal scalp measured by a pulse oximeter just before delivery. The data were collected using an experimental pulse oximeter and a sensor specifically adapted to cope with the problems of fetal pulse oximetry. SETTING: The labour ward in a teaching hospital. SUBJECTS: Thirty seven Caucasian fetuses presenting by the vertex in normal uncomplicated labour. MAIN OUTCOME MEASURE: Fetal pulse oximetry reading shortly before birth, umbilical cord oxygenation and pH, and Apgar scores. RESULTS: Data of sufficient quality were obtained from 28 fetuses. There was a highly significant correlation between pulse oximetry reading and umbilical vein oxygen saturation r = 0.59, P = < 0.001). There was also a significant correlation between the pulse oximeter reading and cord blood pH (vein: r = 0.57, P = 0.002, artery: r = 0.63, P = 0.001). Apgar scores were not related to the oximetry results. CONCLUSION: Pulse oximetry readings reflect fetal oxygenation at birth. PMID- 1420010 TI - A comparative study of the use of epoprostenol and dihydralazine in severe hypertension in pregnancy. AB - OBJECTIVE: To compare the antihypertensive effects of epoprostenol sodium (prostacyclin) with that of dihydralazine in acute hypertensive crises of pregnancy. DESIGN: A prospective randomized study. A minimum of 20 patients per group was considered statistically acceptable (alpha = 0.05, power = 0.9). SETTING: A large urban tertiary hospital. SUBJECTS: Forty-seven pregnant patients with diastolic blood pressures of > 100 mmHg were studied. INTERVENTION: Lowering of high blood pressure with either dihydralazine (n = 25), the standard drug for this purpose, or epoprostenol (n = 22). MAIN OUTCOME MEASURE: A significant drop in high blood pressure was regarded as a fall of 15 mmHg diastolic and 30 mmHg systolic blood pressure. RESULTS: There were no statistically significant differences in the antihypertensive effects between the two treatment groups. Epoprostenol infusion caused less tachycardia; the mean pulse rate changed from 81.77 beats/min, before treatment to 88.36 at stabilization, compared with a change from 80.96 beats/min to 102.68 in the group treated with dihydralazine (P = 0.0024). CONCLUSION: The place of epoprostenol in pregnancy might be in patients with severe hypertension and tachycardia and in those requiring acute control of severe hypertension on the operating table before general anaesthesia. PMID- 1420013 TI - The role of abnormal fetal heart rate in scheduling chorionic villus sampling. AB - OBJECTIVE: To assess the value of fetal heart rate (FHR) measurements in predicting spontaneous fetal loss in pregnancies scheduled for chorionic villus sampling (CVS). DESIGN: A prospective descriptive study. SETTING: Two hospital departments of obstetrics and gynaecology in Israel. SUBJECTS: 114 women between 9 and 11 weeks gestation scheduled for chorionic villus sampling (CVS). INTERVENTIONS: Fetal heart rate was measured by transvaginal Doppler ultrasound and compared with a monogram established from 75 fetuses. Whenever a normal FHR was recorded, CVS was performed immediately. RESULTS: 106 women had a normal FHR and underwent CVS; two of these pregnancies ended in miscarriage. In five pregnancies no fetal heart beats could be identified and fetal death was diagnosed. In three pregnancies an abnormal FHR was recorded and CVS was postponed; all three pregnancies ended in miscarriage within 2 weeks. CONCLUSION: Determination of FHR correlated with crown-rump length could be useful in predicting spontaneous miscarriage before performing any invasive procedure late in the first trimester. PMID- 1420014 TI - Fetal heart rate in early pregnancy and chromosomal disorders. AB - OBJECTIVE: To investigate normal fetal heart rate in early pregnancy and assess the hypothesis that abnormal fetal heart rate is associated with fetal chromosomal abnormalities. DESIGN: Prospective descriptive cross-sectional study. SETTING: Antenatal clinic associated to the University Clinic of Obstetrics, University Hospital Groningen, The Netherlands. SUBJECTS: 424 pregnant women who attended for prenatal counselling. INTERVENTIONS: Measurements of fetal heart rate from 6-16 weeks gestation, cross-sectional study. MAIN OUTCOME MEASURES: Fetal heart rate expressed as beats/min. RESULTS: Karyotyping showed a normal chromosomal pattern in 414 fetuses. The median fetal heart rate increased from 138 beats/min at 6 weeks to 177 beats/min at 9 weeks, thereafter, fetal heart rate gradually decreased to 150 beats/min at 16 weeks. Karyotyping showed 10 abnormalities: five trisomies 21, three trisomies 18, and two mosaic patterns in chorionic villi. Fetal heart rate of the trisomic fetuses was distributed around the median with that of all Down's syndrome fetuses within the normal range. In one fetus with trisomy 18, the heart rate exceeded the 90th centile, in another it fell under the 10th centile. The two fetuses with a mosaic pattern in chorionic villi had heart rates outside the normal range. CONCLUSION: Fetal heart rate in chromosomally abnormal fetuses in early pregnancy do not appear to be consistently different from that in normal fetuses. The use of a single measurement of fetal heart rate is not valuable for screening purposes. Chromosomal mosaicism in chorionic villi may be associated with abnormal fetal heart rate. PMID- 1420015 TI - The prognosis of adenosquamous carcinomas of the uterine cervix. AB - OBJECTIVES: Firstly, to identify a cohort of women with invasive adenosquamous carcinomas of the uterine cervix, including mucin-producing squamous cell carcinomas. Secondly, to compare the biological characteristics and behaviour of a cohort of adenosquamous carcinomas with a cohort of non-mucin-producing squamous cell carcinomas. DESIGN: Histological review, retrospective survival analysis. SETTING: Regional multidisciplinary gynaecological oncology service. SUBJECTS: 161 cases of stage 1B and above invasive cervical carcinoma presenting between 1 January 1980 and 31 July 1987. Thirty nine women with adenosquamous carcinomas were compared with 103 women with non-mucin-producing squamous cell tumours. RESULTS: Inclusion of routine stains for mucin in the assessment of histological material resulted in the reclassification of 38 (24%) of the cases, including the identification of 31 mucin-producing squamous cell carcinomas. The survival with adenosquamous tumours was significantly worse than with squamous cell cancers (P = 0.006), 5-year survival rates being 52% and 75% respectively. Multivariate analysis showed that this effect was explained by differences in clinical stage, pelvic lymph node metastasis and vascular invasion by tumour. CONCLUSIONS: The application of routine mucin stains to cervical tumours identifies a group of previously unrecognized adenosquamous cancers. Tumours so identified are likely to pursue a more aggressive clinical course associated with a poorer survival when compared to non-mucin-producing squamous carcinomas. PMID- 1420016 TI - Increase in bone mass after one year of percutaneous oestradiol and testosterone implants in post-menopausal women who have previously received long-term oral oestrogens. AB - OBJECTIVE: To determine the effect on the bone density of the skeleton after changing from oral oestrogen to subcutaneous oestradiol and testosterone replacement. DESIGN: Prospective non-randomized single centre study. SUBJECTS: Twenty women who were receiving long-term oral oestrogen replacement. Ten changed to oestradiol and testosterone implants; the remaining ten continued with oral oestrogens. MAIN OUTCOME MEASURES: Bone density was measured using dual photon absorptiometry at the lumbar spine and neck of femur at the start of the study and after one year. RESULTS: The bone density increased significantly by 5.7% at the spine and by 5.2% at the neck of femur in those women who changed to implant therapy but remained unchanged in those women who continued with oral therapy. CONCLUSION: Subcutaneous oestradiol and testosterone implants will result in an increase in bone mass even after many years of oral oestrogen replacement therapy. PMID- 1420018 TI - Distribution of renin-containing cells in the developing human kidney: an immunocytochemical study. AB - OBJECTIVE: To characterize the pattern of renin containing cells (RCC) within the human kidney between 20 weeks of gestation and 6 months of postnatal life. DESIGN: Descriptive study using paraffin-embedded blocks of kidney stored following postmortem examination. METHODS: Sections of kidney were stained immunocytochemically using an antibody to human renin; the proportion of RCC within each of three zones (superficial, middle and deep) of the cortex, and their anatomical relation to individual glomeruli were determined. The cases were divided into five groups for analysis to gestational or postnatal age. RESULTS: Fetal RCC were usually at the vascular pole of the most mature glomeruli within the deeper areas of the cortex and were occasionally located within glomeruli. This distribution persisted until birth, even when the kidney was histologically mature. By contrast there were fewer RCC in neonatal and infant kidneys and, as in adult kidneys, these were located predominantly in the superficial cortex. CONCLUSION: The change in RCC distribution around the time of normal birth may relate to the transition to independent renal function. The location and density of RCC during fetal life may influence renal perfusion and amniotic fluid production. PMID- 1420019 TI - The use of a tissue expansion technique in the reconstruction of the female genitalia in bladder exstrophy. PMID- 1420017 TI - Plasma endothelin, atrial natriuretic peptide (ANP) and uterine and umbilical artery flow velocity waveforms in hypertensive pregnancies. AB - OBJECTIVE: To investigate the relation between concentrations of endothelin and atrial natriuretic peptide (ANP) in maternal plasma and vasospasm in the uterine and umbilical arteries as detected by duplex pulsed colour Doppler ultrasonography in hypertensive pregnancies. DESIGN: An observational study. SUBJECTS: 32 women admitted consecutively to hospital with pregnancy induced hypertension (seven without proteinuria and 25 with proteinuria) and 78 healthy pregnant women examined at 28-40 weeks gestation. MAIN OUTCOME MEASURES: Systolic/diastolic (S/D) ratio in flow velocity waveforms (FVWs) and plasma concentrations of endothelin and ANP in the 32 women with pregnancy induced hypertension; plasma concentrations of endothelin and ANP in 78 healthy pregnant women (controls). RESULTS: Pathological FVWs suggesting vasospasm in the uterine or umbilical artery, or both arteries, were found in 12 women with hypertension. Plasma ANP was significantly higher (P = 0.03) in the women with hypertension and pathological FVWs (median 23.0, range 10.1-52.8 pmol/l) than in those with hypertension and normal FVWs, (median 13.8, range 5.3-42.3 pmol/l) but corresponding plasma endothelin levels did not show any significant difference (median 1.63, range 0.51-3.33 pmol/l and median 1.38, range 0.51-3.51 pmol/l, respectively). CONCLUSION: Local release of endothelin from the vascular endothelium is thought to cause vasospasm in pregnancy induced hypertension but this does not seem to increase the concentration of endothelin in the maternal peripheral plasma, probably because of its rapid disappearance from the blood circulation. As ANP dilates the blood vessels, the increase of its release in hypertensive pregnancies may be a compensatory mechanism against vasospasm. PMID- 1420020 TI - Endometrial decidual changes in a postmenopausal woman treated with tamoxifen and megestrol acetate. PMID- 1420021 TI - Renal cell carcinoma: an unusual cause of second trimester hypertension. PMID- 1420022 TI - Randomized placebo controlled trial to assess the role of intracervical lignocaine in outpatient hysteroscopy. PMID- 1420023 TI - Breech delivery and epidural analgesia. PMID- 1420024 TI - Breech delivery and epidural analgesia. PMID- 1420025 TI - ST-waveform analysis of the fetal electrocardiogram could reduce fetal blood sampling. PMID- 1420026 TI - Intra-operative blood loss during elective lower segment caesarean section. PMID- 1420027 TI - [Infection status of the sea eel (Astroconger myriaster) purchased from the Noryangjin fish market with anisakid larvae]. AB - Although the sea eel (Astroconger myriaster) is suspected as one of the most important fish host for human anisakiasis in Korea, no report has been made on the infection status of the sea eel with anisakid larvae. In the present study, 26 sea eels (Astroconger myriaster) were purchased from the Noryangjin fish market in Seoul, and anisakid larvae were collected from their viscera, muscle, head and skin. The collected larvae were classified by their morphological types. A total of 1,351 anisakid larvae were collected from 15 of 26 fish examined. Among them, 1,269 were recovered from the viscera, 66 from the muscle, and 16 from the head and skin. Morphologically, most of the anisakids were classified into 6 known larval types, Anisakis type I (564 larvae) of Berland (1961), Contracaecum type A (409) and type D (5) of Koyama et al. (1969), Contracaecum type C' (83) and type D' (117) of Chai et al. (1986), and Contracaecum type V (1) of Yamaguti (1935). Remaining 172 specimens were new in the available literature, hence, designated as Contracaecum type A' (new type). The present results revealed that the sea eels caught in the Korean waters are heavily infected with anisakid larvae, not only in their viscera but also in the muscle, and Anisakis type I was the most common among the 7 larval types. PMID- 1420028 TI - [Enterobius gregorii Hugot, 1983 recovered from school children in Kangwon-Do, Korea]. AB - Hugot (1983), Hugot and Tourte-Schaefer (1985) reported that nematodes of the genus Enterobius causing human enterobiasis might be classified into two different species on the basis of the size and shape of spicule in male worms. E. gregorii Hugot, 1983 has significantly shorter spicules in males than those in E. vermicularis. A total of 194 male Enterobius were collected from 17 schoolchildren by anthelmintics at Wonju, Kangwon-do. The sizes of spicules and morphologies were comparatively observed. Two different types of spicules in male Enterobius were also observed in Korea. Out of 112 male worms observed, the percentages of E. gregorii (short-spicule type) and E. vermicularis (long-spicule type) were 23.2% and 76.8%, respectively. PMID- 1420029 TI - Egg production of Clonorchis sinensis in different strains of inbred mice. AB - In order to compare the intraspecific variation in host-parasite relationship of Clonorchis sinensis, six strains of inbred mice, ICR, DDY, GPC, BALB/c, nude and DS, were infected orally with 20 metacercariae of C. sinensis. The biologic incubation period of C. sinensis was the shortest in DDY mice, 21.2 days in average, followed by GPC 21.4, BALB/c and DS 23.2, ICR and nude 23.4 days, respectively. The fertile period of the fluke was also the longest in the DDY strain, 164 days on average, followed by GPC 132, BALB/c 97, nude 37, DS 32 and ICR 28 days. The egg-laying capacity of the fluke in DDY and GPC was relatively high and stable compared with the other four strains of mice. It was found that there are intraspecific variations in biologic incubation period, fertile period, and fecundity of C. sinensis. The DDY mouse is likely to be the most suitable experimental animal among the six strains of the mice tested. PMID- 1420030 TI - Platelet kinetics and other hematological profiles in experimental Plasmodium falciparum infection: a comparative study between Saimiri and Aotus monkeys. AB - Levels of platelets and other hematological values were monitored in 21 Saimiri and 12 Aotus monkeys over a period of three weeks post-infection with monkey adapted Indochina CDC-1 strain of Plasmodium falciparum. In both Saimiri sciureus boliviensis and Aotus nancymai karyotype-1 monkeys the severest thrombocytopenia was observed at 14 days post-infection coinciding with peak parasitemia, neutropenia, lymphocytosis, and anemia associated with severe hemoglobinemia and elevated fibrinogen degeneration products(FDP's). MCH and MCV profiles in Aotus monkeys decreased with ascending parasitemia. In contrast, these parameters in Saimiri were characterized by a significant compensatory increase correlating with parasitemia. In general, thrombocytopenia was one of the earliest clinical manifestations of the infection with the platelets returning to normal levels shortly after peak parasitemia at 14 days. Platelet kinetics had a strong correlation with hematologic and parasitologic values in the Aotus model. No consistent associations were observed between platelet kinetics and other parameters in the Saimiri model. These data indicate that the Aotus model for malaria is more predictable than the Saimiri. Further, platelet turnover rates and recovery provide a useful prognostic parameter during malaria infection. The results are discussed in relation to the value of the two species of monkeys as models for the pathogenesis of human malaria. PMID- 1420031 TI - Karyotypes of Pneumocystis carinii from Korean rats. AB - Molecular karyotyping was applied to Pneumocystis carinii(Pc) from two strains of experimental rats, Sprague Dawley(SD) and Fisher(F), in Korea. Field inversion gel electrophoresis and contour clamped homogeneous electric field electrophoresis resolved 15 chromosomal bands from the Pc. The size of the bands was estimated 270kb to 684kb from SD rats, and 273kb to 713 kb from F rats. The bands of 283 kb from SD rats and of 273 kb from F rats stained more brightly suggesting duplicated bands. Total number of chromosomes was at least 16, and total genomic size was estimated 7 x 10(6) bp. All of the bands from F rats hybridized to the probe of repeated DNA sequences of Pc and the band of 448 kb size was proved to contain rDNA sequences, but Pc. chromosome bands from SD rats showed no reactions to the probes. The 2 different karyotypes of P. carinii from 2 strains of rats were maintained consistently for 2 years. PMID- 1420032 TI - Isolation and partial characterization of cysteine proteinase from sparganum. AB - A proteolytic enzyme was purified from the tissue extract of spargana (plerocercoids of Spirometra erinacei) by DEAE-Trisacryl M ion exchange chromatography and thiopropyl-sepharose affinity chromatography resulted in a 21 fold purification. The proteinase activity was assayed with a synthetic fluorescent substrate, carbobenzoxy-phenylalanyl-7-amino-4-trifluoromethyl coumarin. SDS-polyacrylamide gel electrophoresis of the purified materials revealed a single 28,000 dalton band. Inhibitor profiles of the band indicated that it belonged to cysteine endopeptidases. It exhibited identical pH curves with optimum at pH 5.5, and 50% activity from pH 4.7 to 8. It could completely degrade collagen chains to three identical products. It also showed some activity on hemoglobin. Furthermore, the band on immunoblots was reactive to the sera of sparganosis patients. These results suggest that the proteolytic enzyme belongs to cysteine proteinase which plays a role in the tissue penetration. Also it may be used as the antigen for diagnosis of active sparganosis. PMID- 1420033 TI - Immunogenicity and protective efficacy of solubilized merozoite-enriched Theileria sergenti immunogens. II: Protection against natural exposure under field conditions. AB - A Theileria sergenti soluble merozoite preparation containing the 29, 34, 35 and 105 KD as the immunodominant polypeptides, was evaluated for efficacy, safety and protectivity in Holstein calves against virulent field tick challenge. The soluble antigens (100 mg/dose) were fortified with either complete or incomplete Freund's adjuvant. Twenty naive calves, aged one month, were subcutaneously inoculated with the preparation and a booster dose was administered 4 weeks later. Twenty additional calves served as controls. Five weeks after the booster dose, vaccinates and uninoculated controls were moved to a pasture, a heavily tick infested area in Cheju-do, Korea. The vaccinates showed negligible change in hematocrit and total RBC count whereas control animals showed significant (p < 0.05) hematological changes and associated anemia. Only 30% of vaccinates required chemotherapy after the experiment was terminated. All control animals required chemotherapy and 25% received blood transfusion. The highest percent parasitized erythrocytes in vaccinated cattle was 0.4% as compared with 3.6% among controls during the month of July. A significant difference (p < 0.05) was observed in the rate of body weight increase. Significant differences were also noted in serum albumin, aspartate aminotransferase, total protein and bilirubin. Significantly more vaccinated cattle maintained normal ranges of hematological and biochemical values as compared with the control group. It is suggested that soluble merozoite T. sergenti antigens may be potential vaccine candidates for developing a genetic vaccine in Korea. PMID- 1420034 TI - Immunoelectrophoretic analysis of major component proteins in cystic fluid of Taenia solium metacestodes. AB - When cystic fluid of Taenia solium metacestodes (CF) was filtrated through Sephacryl S-300 Superfine, major proteins were in fractions III and IV. Major protein in fraction III was Band C protein of 150 kDa and that in fraction IV was Band N protein (Choi et al., 1990). When CF was electrophoresed in 0.9% agarose gel and reacted with anti-CF rabbit serum (RACF), two main bands, a long outer and a short inner band, were precipitated, together with 8 minor bands. RACF reacted with fraction III forming the long outer band whereas RACF formed the short inner band with fraction IV in immunoelectrophoresis (IEP). The long outer precipitin band of CF fraction III was similar to antigen B in hydatid fluid (HF) of Oriol et al. (1971), while the short inner band of CF fraction IV was similar to HF antigen 5 of Capron et al. (1967). When HF was reacted with RACF, the short inner band was immunoprecipitated without forming the long outer band. Common antigenicity between CF and HF seemed to exist in fraction IV rather than in fraction III of CF. Patient sera of neurocysticercosis reacted more frequently with fraction III than with fraction IV. PMID- 1420035 TI - Component proteins and protease activities in excretory-secretory product of sparganum. AB - Spirometra mansoni plerocercoid (sparganum) was incubated in saline at 4 degrees C or 37 degrees C up to 100 hours. Protein contents in the excretory-secretory product (ESP) were rather constant (mean 7.7 mg of protein/gram of sparganum) in the preparations. Reducing SDS-PAGE of ESP showed similar protein subunit compositions with those in crude extract. Antigenic 36 and 31 kDa proteins were major bands in ESP. ESP exhibited specific activities of protease (2.9-5.3 units/mg) at pH 6.0 and pH 7.5. Presence of protease activity in ESP may be a supporting evidence that hitherto known cysteine protease of sparganum is possibly secreted. PMID- 1420036 TI - [A case of strongyloidiasis accompanied by duodenal ulcer]. AB - A 58-year-old chronic alcoholism patient, who complained of epigastric discomfort, nausea, and frequent loose stool was diagnosed as strongyloidiasis accompanied by duodenal ulcer. The symptoms first appeared two years ago and aggravated during the recent 3 months, and he lost 4 kg of his body weight. Stool examination revealed rhabditoid nematode larvae, which were confirmed as those of Strongyloides stercoralis after cultivation of them to filariform larvae. At duodenoscopy, duodenal ulcer was found. The patient was treated with albendazole (200 mg, bid, for 14 days) for strongyloidiasis and with colloidal bismuth sulfate (240 mg, bid, for 6 weeks) for duodenal ulcer. After the medication, the symptoms of loose stool and epigastric discomfort were much improved and he was discharged with no clinical problems. This is an interesting case which suggests that S. stercoralis infection could be related with ulceration of the duodenal mucosa. PMID- 1420037 TI - The red eye of renal failure: a crystal induced inflammation? AB - Of 57 patients with chronic renal failure and calcification of the anterior membranes of the eye eight developed inflammatory reactions, clinically indistinguishable from pingueculitis. In three patients an acute inflammatory reaction of the episcleral tissue and the conjunctiva over it developed which we considered to represent the red eye of renal failure. In these patients massive shedding of calcium phosphate salts was clinically evident. Histopathologically in all these patients calcific deposits were observed. Although sporadically polymorphonuclear leucocytes were present in the inflamed tissues we could not demonstrate crystal phagocytosis. We believe that in the red eyes in renal failure and, more specifically, in the red eyes of renal failure a crystal induced inflammatory mechanism is not operative. PMID- 1420039 TI - Radial keratotomy: a review of 300 cases. AB - Three hundred consecutive cases of radial keratotomy performed between 1985 and 1990 were reviewed. There were no sight threatening complications of surgery and no patient lost one or more lines of corrected Snellen acuity. Overall 78.7% saw 6/12 or better unaided postoperatively and 51.7% saw 6/6 or better. Refraction showed 61.3% to be within 1 dioptre of emmetropia and 86.7% were within 2 dioptres. Further analysis demonstrated that results of unaided acuity and proximity to emmetropia were much better for low (< -2.87 D) and moderate (-3.0 to -5.87 D) than for high (> -6.0 D) myopes. PMID- 1420038 TI - Herpetic keratitis in Tanzania: association with malaria. AB - Of 103 patients who presented to a rural clinic in Africa with corneal ulceration, 62 (60.2%) had corneal ulcers which on clinical diagnosis were attributable to herpes simplex virus. There was a strong association between herpetic ulceration and a history of recent malaria; 37 of 62 (59.7%) herpetic ulcers occurred in the 3 month period from April to June which corresponds to the end of the peak season for malaria compared with 14 of 41 (34%) of the non herpetic ulcers. Fifty per cent of herpetic ulcers had a geographic morphology, 27.4% were dendritic, and 22.6% presumed herpetic ulcers were stromal: 38.7% of herpetic ulcers occurred in children under 5 years of age. Bilateral herpetic ulcers occurred in 16.1% of patients but were more common in children under 2 years of age. Geographic and stromal ulcers tended to heal more slowly than dendritic ulcers (mean time to healing 12.6, 12.2, and 6.6 days respectively), and were more likely to result in severe corneal scarring (45%, 29%, and 0% respectively). Herpes simplex keratitis is a major cause of corneal scarring in Africa. It is often seen in children, may be bilateral, commonly is geographic in morphology, and has a strong association with malaria infection. Because it is not easily preventable, more effort must be made to ensure early diagnosis and prompt, effective treatment in order to prevent severe scarring and visual loss. PMID- 1420040 TI - Life expectancy in keratoconus. AB - It is observed that few patients over the age of 60 regularly attend the keratoconus clinic at Moorfields Eye Hospital. The hypothesis that patients with keratoconus have a shorter life expectancy owing to underlying connective tissue related disease was tested. From patient records a sample of 337 keratoconus patients aged at least 40 years by 1991 were identified, of which 279 were living, 13 were deceased, and 45 were untraceable. The mortality rate for keratoconus patients was compared with that of the general population using actuarial English life tables. Results show no significant difference between the general population mortality rate and that of the keratoconus sample even with adjustment for social class. Possible explanations for the non-attendance of older patients are discussed. PMID- 1420042 TI - Intravenous sedation for ocular surgery under local anaesthesia. AB - Anterior segment ophthalmic surgery is commonly performed under local anaesthesia. In order to improve patient comfort, a variety of sedation techniques has been employed in the past. The object of this study was, firstly, to determine whether continuous intravenous sedation during surgery offered any advantages in patients premedicated with temazepam and metoclopramide, and, secondly, to compare midazolam to propofol for this purpose. Forty nine patients were randomly allocated to receive no intravenous sedation (n = 15), continuous propofol infusion (n = 17), or continuous intravenous midazolam infusion (n = 17) after peribulbar anaesthesia. Each technique provided cardiovascular and respiratory stability and allowed early recovery with minimal postoperative sequelae. Unexpected ocular field movement occurred more commonly in the patients receiving intravenous sedation, although statistical significance was not shown (p = 0.06). Significantly more patients in the intravenous sedation groups reported amnesia (p = 0.03). Patient acceptability was good irrespective of the technique used. This study suggests that continuous sedation using propofol or midazolam is not beneficial and should be avoided in ophthalmic patients who have received a simple premedication. PMID- 1420041 TI - Foveal photopigment kinetics--abnormality: an early sign in myotonic dystrophy? AB - Twelve subjects with minimal expression of the myotonic dystrophy (MyD) gene were investigated by retinal densitometry, a technique which has been used to study the properties of photopigments in the living eye and to detect photoreceptor abnormalities. Other investigations included slit-lamp examination, funduscopy, raleigh matches with the anomaloscope, tonometry, and neurological examination, including electroretinography (ERG) and pattern visual evoked potentials recording. Foveal densitometry demonstrated reduced values of the macular photopigment density difference with normal photopigment kinetics in early phases of the disease, even in asymptomatic individuals. The densitometric values correlated with decreased amplitudes of the photopic ERG a-wave. These findings may be explained by loss or dysfunction of the outer segments of foveal receptors. It is yet unknown whether or not these changes are secondary to other observed neuroretinal abnormalities in MyD. The most likely explanation might be an abnormality of the Na, Ca:K exchanger at the level of the outer segments of the photoreceptors whether or not in combination with a dysfunction of voltage generation systems, involving both photoreceptors and retinal pigment epithelium. PMID- 1420043 TI - Type IV collagen and laminin in Bruch's membrane and basal linear deposit in the human macula. AB - Tissue obtained from the macula in 10 human eyes (53-77 years) was used for an investigation into the extracellular matrices of the retinal pigment epithelium (RPE), Bruch's membrane, and the choriocapillaris. The ultrastructural distribution of type IV collagen and laminin was documented using immunogold labelling. Labelling for type IV collagen was strongly positive in all the specimens in the basement membranes of the choriocapillaris but not that of the RPE where labelling was either weak or absent. Laminin was localised to deposits of granular material in Bruch's membrane but was absent from the basement membrane of the RPE and the choriocapillaris. Basal linear deposit, observed in three cases, demonstrated labelling for laminin but not for type IV collagen. The series was too small for correlation of these morphological changes with age. PMID- 1420044 TI - Induced chorioretinal venous anastomosis in experimental retinal branch vein occlusion. AB - Iatrogenic retinal vein to choroidal vein anastomoses were created using laser photocoagulation in six of seven dog eyes in which a partial branch retinal vein occlusion had previously been created photochemically. A similar attempt to create an anastomosis was made in six control eyes in which no branch vein occlusion was present. In the eyes in which a branch retinal vein had been created, a venous chorioretinal anastomosis appeared to be present by 3 to 6 weeks. In three control eyes similar venous anastomosis was created; however this took 6 to 8 weeks to develop and was of much smaller calibre than the one that developed in the presence of a partial branch retinal vein occlusion. No adverse complications were noted in the period of the study (3 months). This study demonstrates that chorioretinal venous anastomoses can be created and may be of use in the treatment of partial retinal vein occlusions that show signs of progression. PMID- 1420045 TI - AgNOR counts in conjunctival malignant melanoma lack prognostic value. AB - Using a silver staining technique, argyrophilic nucleolar organiser region associated proteins (AgNORs) have been studied in routinely processed paraffin sections of 46 invasive malignant melanomas (MM) of the conjunctiva. The aim of this retrospective study was to assess the value of the AgNOR method as a prognostic indicator for this neoplasm. The 46 cases were divided into two groups: (A) 14 cases of MM that metastasised and caused death of the patient within 5 years of (histological) diagnosis, and (B) 32 cases of MM that did not metastasise and in which patients survived beyond 5 years. The mean of the AgNOR counts per nucleus was 7.03 (95% CI: 5.81-8.24) in group A, and 7.15 (95% CI: 6.53-7.77) in group B. A comparison using a multifactor analysis of variance (ANOVA) model, which corrected for possible confounding effect of tumour thickness, site, and cell type showed no significant difference in AgNOR counts between groups A and B (p = 0.8). Analysis by the Cox proportional hazards regression model showed that survival was not influenced significantly by the mean AgNOR number (hazard ratio: 0.92). Whereas the AgNOR technique may be used to distinguish benign from malignant melanocytic lesions of the conjunctiva, we conclude it has no value in predicting the outcome for patients with conjunctival MM. PMID- 1420046 TI - Laser trabeculoplasty. AB - Using the now well established technique ALT is a safe and effective means of lowering IOP in eyes with POAG, pigmentary glaucoma, and exfoliative glaucoma though the effect diminishes with time. Pressure reduction with ALT is seldom greater than 30% and eyes with an IOP of more than 28 mm Hg are unlikely to be controlled for any length of time without additional treatment. ALT is probably most suitable either for older patients whose glaucoma is not well controlled on medical treatment, or for patients with newly diagnosed open angle glaucoma, but without advanced field loss, as a primary treatment or in combination with a non miotic topical medication. In many it will defer surgery, in some indefinitely. PMID- 1420049 TI - Acyclovir in herpes zoster ophthalmicus. PMID- 1420048 TI - Vanishing retinal arterial aneurysms: a case report. AB - An 18-year-old woman with retinal vasculitis developed multiple retinal arterial aneurysms over a period of 3 years. Subsequently she developed macular oedema, peripheral neovascularisation, and vitreous haemorrhage and was treated with systemic steroids, laser photocoagulation, and vitreoretinal surgery. No systemic cause for vasculitis was found. Serial fluorescein angiography demonstrated gradual resolution of the arterial aneurysms over the subsequent 7 years. PMID- 1420047 TI - Bilateral multiple cavernous haemangiomas of the orbit. AB - Orbital cavernous haemangioma, a common orbital tumour, is usually single and unilateral. We report the first case of histologically confirmed bilateral multiple cavernous haemangiomas of the orbit. PMID- 1420050 TI - Sir William Bowman. PMID- 1420051 TI - Heavy liquids for postoperative tamponade. PMID- 1420052 TI - The electro-oculogram in central retinal vein occlusion. AB - As part of a prospective masked study, the electro-oculogram (EOG) was recorded from 28 patients within 48 days of developing central retinal vein occlusion (CRVO). The EOG light peak/dark trough ratio (Lp/Dt) x 100 was significantly lower in the affected than in the unaffected eyes of patients (p < 0.001), and abnormally low in absolute terms in 20 patients (71%). All unaffected fellow eyes had a normal EOG ratio. The mean Lp amplitude of affected eyes was significantly smaller than that of unaffected eyes (p < 0.001), whereas the differences in mean Dt amplitudes between affected and unaffected eyes were not statistically significant. The Lp amplitude in the affected eye was 48% or less of that in the unaffected eye in the eight patients (29%) who developed rubeosis iridis during the 9 month follow-up, and in six others. No patient whose Lp amplitude in the affected eye was greater than 48% of that in the unaffected eye, developed rubeosis. It is concluded that the Lp amplitude is abnormal in patients with acute CRVO. The degree of this abnormality bears a relation to the development of rubeosis, which might prove a useful indicator of whether to institute or withhold panretinal photocoagulation. PMID- 1420053 TI - Controlled study of ocular morbidity in school children born preterm. AB - Two hundred children who were of very low birth weight (VLBW) (1500 g or less) and 193 controls who were of normal birth weight (NBW) were examined at approximately 9 years of age. Binocular visual acuity of 6/6 or better was noted in 178 (89.5%) VLBW children and 189 (97.9%) NBW children. Visual morbidity was significantly higher among VLBW children. Strabismus was present in 38 (19%), cicatricial retinopathy of prematurity in 13 (6.5%), and optic atrophy in six (3%) children in this group. Children who were VLBW were also more myopic than the NBW controls. Optic atrophy was frequently associated with cerebral dysfunction. Regular assessments to identify ocular abnormalities in children who were VLBW are recommended. PMID- 1420054 TI - Vitreon, a short-term vitreoretinal tamponade. AB - This investigation of the liquid perfluorocarbon, perfluorophenanthrene (Vitreon), establishes its safety and efficacy as a short-term vitreoretinal tamponade. We utilised Vitreon as an intraoperative tool and postoperative vitreoretinal tamponade in 16 patients. Proliferative vitreoretinopathy (PVR) (six), giant retinal tear (four), rhegmatogenous retinal detachment (three), retinal detachment with keratoprosthesis (two), and submacular and vitreous haemorrhage (one) were successfully repaired. Vitreon was left in the eye and removed 5 days to 4 weeks postoperatively. Complications encountered included proliferative PVR (five), limited peripheral retinal detachment (three), macular pucker (two) cataract (three), hypotony (two), excessive fibrin reaction (one), and elevated intraocular pressure (one). At the latest evaluation, all retinas are attached with a follow-up of 1.25 to 12 months (mean 6.8 months). PMID- 1420056 TI - Cautery for lower lid entropion. AB - A prospective study was undertaken to evaluate a simple cautery technique for the correction of involutional lower lid entropion in 50 patients. After a 12 month follow-up period all patients were free of entropion. Only one patient needed to have the procedure repeated because of recurrence. The technique was found to be simple, effective, safe, and required very little time and skill. PMID- 1420055 TI - Ocular circulatory changes following scleral buckling procedures. AB - The effect of segmental scleral buckling (SB) on ocular circulation was evaluated by measurements of the ocular pulse amplitude (PA) and the ophthalmic artery pressure (OAP). In this study the OAP was defined as the intraocular pressure (IOP) at which the PA disappeared during increasing IOP. Twenty four patients with unilateral rhegmatogenous retinal detachment who underwent SB of varying extent were studied; the unoperated fellow eyes served as controls. Both the OAP and the ophthalmic perfusion pressures (OAP minus IOP) decreased significantly (p < 0.01) as the area of SB treatment increased. Follow-up measurements showed that the OAP was relatively lower up to 3 months postoperatively than after 3 months, and then remained stable. Our results indicated that SB affects the ocular pulse measurements and may decrease ocular blood flow because of decreased ophthalmic perfusion pressure, probably due to increased choroidal vascular resistance, and that the greater the extent of the SB treatment, the greater the possibility of decreased ocular blood flow. PMID- 1420058 TI - Tono-Pen tonometry in normal and in post-keratoplasty eyes. AB - Oculab Tono-Pen tonometry was compared with Goldmann applanation tonometry in 82 eyes of 82 patients with normal corneas and in 54 eyes of 54 patients who had undergone penetrating keratoplasty and whose corneas did not preclude the use of Goldmann tonometer. We found that the intraocular pressure (IOP) in 48% of the eyes with normal corneas and in 57% after keratoplasty has different measurements with Goldmann and Tono-Pen pressures of 3 mm Hg or more. Despite the correlation between the Goldmann tonometer and the Tono-Pen in the group of eyes with normal corneas (r = 0.83) as well as in the group of eyes after keratoplasty (r = 0.79) the Tono-Pen tended to significantly overestimate the Goldmann tonometer reading (p < 0.0001). The mean difference between the two instruments was highest across the lower IOP range (< 9 mm Hg) in the group of eyes after keratoplasty. Because the mean absolute values of the paired differences between Goldmann and Tono-Pen measurements varied significantly across all IOP intervals it was not possible to establish a correction factor which could be used when comparing the two measurements. Based on this study the Tono-Pen consistently overestimated the actual IOP in an unpredictable manner. Where possible Goldmann measurements of the IOP are still to be preferred. PMID- 1420057 TI - Prevention of acute postoperative pressure rises in glaucoma patients undergoing cataract extraction with posterior chamber lens implant. AB - Acute elevations in intraocular pressure (IOP) commonly follow extracapsular cataract extraction and lens implant in glaucoma patients. Thirty six patients with glaucoma undergoing cataract extraction and posterior chamber lens implantation received one of three treatments. Group 1: 500 mg of Diamox Sustets (acetazolamide) 1 hour preoperatively (10 patients); Group 2: peroperative intracameral Miochol (acetylcholine) (11 patients); Group 3: the above treatments combined (15 patients). IOPs were measured at 3, 6, 9, and 24 hours postoperatively. The average of the maximum pressure rises above the preoperative level over the 24 hour period was greatest for the group receiving acetazolamide only at 8.9 mm Hg; for the acetylcholine group the average maximum rise was 6.3 mm Hg; while the combined treatment group showed a decrease of 0.7 mm Hg. IOP rises of > 6 mm Hg were seen in 7% of patients (one of 15) in the combined treatment group, 45% (five of 11) of the acetylcholine group, and 70% (seven of 10) of the acetazolamide group. IOP rises of > 10 mm Hg were seen in 7% of the combined treatment group, in 18% of the acetylcholine only group, and in 50% of the acetazolamide only group. A pressure rise > 20 mm Hg was seen in one patient receiving acetazolamide only and one patient receiving acetylcholine only. The difference between the acetylcholine group and the combined group for rises > 6 mm Hg was significant using the chi 2 test while the acetazolamide group showed a significant difference for rises > 6 and 10 mm Hg compared with the combined group. All acute pressure rises were recorded before or at 9 hours following operation except in the combined treatment patient where the rise occurred at 24 hours. To prevent the acute IOP rises seen following cataract surgery with lens implant in glaucoma patients we recommend combined ocular hypotensive therapy. PMID- 1420059 TI - Visual evoked potentials after retrobulbar or periocular anaesthesia. AB - The effect of the local anaesthetic agent, etidocaine, on the optic nerve function was examined at regional ophthalmic anaesthesia. Visual evoked potential (VEP) was recorded before and 15 minutes after injection of the anaesthetic agent in 19 patients scheduled for elective cataract surgery (seven retrobulbar and 12 periocular). Both the anaesthetised--that is, the eye to be operated on--and the fellow eye were examined. In the retrobulbar group, two patients displayed non recordable VEPs while one had virtually non-detectable waves following the anaesthesia. In two retrobulbarly anaesthetised eyes, later peaks were unidentifiable while two other eyes had decreased amplitudes. In the periocular group, in nine patients, there was no clearcut effect on VEP resulting from the anaesthetic. In three patients of this group mild changes in the anaesthetised eyes were found. The differences in the effect of retrobulbarly or periocularly injected anaesthetics on VEP are probably due to the different concentration of the anaesthetic agent around the optic nerve. PMID- 1420061 TI - Proliferative retinal diseases: myofibroblasts cause chronic vitreoretinal traction. AB - Myofibroblasts are contractile cells having features intermediate between those of the fibroblast and smooth muscle. Myofibroblasts in preretinal membranes may cause retinal traction in proliferative retinal diseases. In this study, we demonstrate the presence of a chronically contractile subpopulation of myofibroblasts in pre-retinal membranes. Apha smooth muscle actin or desmin, both markers of the myogenically differentiated and chronically contractile subpopulation could be detected in a large majority of the examined membranes. Our findings may serve to explain the cellular basis of vitreoretinal traction in proliferative vitreoretinopathy and proliferative diabetic retinopathy. PMID- 1420060 TI - Immunopathological findings in conjunctival cells using immunofluorescence staining of impression cytology specimens. AB - The conventional technique of impression cytology provides a non-invasive method for the evaluation of conjunctival epithelium alterations. Using indirect immunofluorescence procedures two inflammatory markers, class II MHC antigens HLA DR and the receptor to IgE (CD23), were sought in impression cytology specimens obtained from 80 patients. In normal subjects conjunctival epithelial cells did not show any reactivity. Only scattered dendritic cells were found to express class II antigens but not the receptor to IgE. In contrast patients with chronic conjunctivitis of various aetiologies, mainly infectious or allergic, had 40-100% of brightly positive conjunctival cells for one or both antigens. In these cases epithelial cells and goblet cells reacted similarly. Twenty four eyes in 12 patients with idiopathic dry eye syndrome disclosed results similar to those from normal conjunctival specimens. However 18 other specimens from patients suffering from idiopathic tear deficiency but undergoing multiple substitutive treatments for dry eye had moderate to strong positivity for HLA DR and/or the receptor to IgE (20-100% of cells). As these results were independent of the degree of squamous metaplasia the expression of these membrane markers may reflect local inflammation in addition to tear deficiency, possibly due to sensitisation to the eye drops used. These immunocytological techniques thus provide useful methods of investigating conjunctival inflammation and allergy. They may constitute valuable aid in the diagnosis and appropriate treatment of ocular surface disorders. PMID- 1420062 TI - Experimental autoimmune uveoretinitis in the RCS rat: the influence of photoreceptor degeneration on disease expression. AB - S-antigen induced experimental autoimmune uveoretinitis (EAU) was produced in the Royal College of Surgeons (RCS) strain of rat which develops a photoreceptor dystrophy within 2 weeks of birth. Animals were sensitised at 60, 90, and 105 days of age: all animals developed disease, but onset was significantly delayed in older (105 day) animals compared with those aged 60 days at sensitisation (p 0.003). Disease was characterised by the early development of complete serous retinal detachment which resolved in a few days: the prevalence of retinal detachment was increased to 80% in dystrophic animals compared with 10% in the congenic, non-dystrophic controls (p < 0.001). Anterior uveitis was seen in 17/30 control strain eyes, but in none of 30 dystrophic eyes (p < 0.001). Genetically determined photoreceptor and retinal pigment epithelium dysfunction in the RCS rat, which may involve the local accumulation of altered S-antigen, predisposes the dystrophic strain to display an acute retinal detachment in the early stages of EAU. This phenomenon illustrates how biochemical dysfunction of a target organ may influence susceptibility, form, and severity of an experimental autoimmune disease. PMID- 1420063 TI - Adjustable sutures in squint surgery. PMID- 1420064 TI - Congenital adenoma of the iris and ciliary body: light and electron microscopic observations. AB - A 23-year-old man had a lesion in the right inferior iris which appeared to have enlarged since it was first seen when the patient was aged 5 years. The lesion was excised by a partial iridocyclectomy. Histopathologically the neoplasm was composed of both pigmented and non-pigmented cells. Pseudoacini, containing acid mucopolysaccharides, were present throughout the tumour matrix. Electron microscopically the non-pigmented cells were found to possess a convoluted plasmalemma, abundant rough endoplasmic reticulum, and numerous desmosomes and gap junctions. The pigmented cells contained large, round, mature melanosomes, occasional premelanosomes, and desmosomes, which resembled the posterior pigment epithelium of the iris. The intercellular matrix contained fine collagen fibrils resembling vitreous. We believe that this neoplasm represents a congenital adenoma of the ciliary body and iris. PMID- 1420065 TI - Ciliary block (malignant) glaucoma after cataract extraction with lens implant treated with YAG laser capsulotomy and anterior hyaloidotomy. AB - An 84-year-old woman developed high intraocular pressure with a shallow anterior chamber 2 months after an extracapsular cataract extraction with posterior chamber lens implant. The condition did not respond to peripheral iridectomy and removal of the implant but was treated successfully with YAG laser capsulotomy and anterior hyaloidotomy. PMID- 1420066 TI - Late onset Leber's optic neuropathy: a case confused with ischaemic optic neuropathy. AB - A case is reported of a 63-year-old man with progressive central visual loss in one eye followed 11 months later by involvement of the fellow eye. A diagnosis of chronic ischaemic optic neuropathy was considered. However, despite a negative family history, the absence of electrocardiographic abnormalities, and minimal fundus changes a diagnosis of Leber's optic neuropathy was made on the basis of magnetic resonance imaging findings and the mitochondrial DNA mutation at base pair 11778. PMID- 1420067 TI - Concurrent uveoretinitis and pineocytoma in a child suggests a causal relationship. AB - Uveoretinitis was observed in a 9-year-old girl 6 months prior to the clinical appearance of a pineal tumour. Surgical removal was not successful but biopsy revealed a parenchymal neoplasm with differentiated pinealocytes and absent mitotic activity. Some of the tumour cells contained S-antigen, rhodopsin, and serotonin. Systemic glucocorticoid therapy followed by radiation therapy caused considerable reduction in size of the tumour and a complete normalisation of all eye symptoms. This report demonstrates for the first time that a pineocytoma can occur together with uveoretinitis in humans. The latter resembles the experimentally induced autoimmune uveoretinitis described in animals. It is speculated that the retinitis might reflect an autoimmune response to S-antigen present in some tumour cells of the pineocytoma. PMID- 1420069 TI - Plasma concentrations of fat-soluble vitamins A and E in neonates with myelomeningocele. AB - A group of newborn infants with myelomeningocele was compared with a group of neonates suffering from gastrointestinal malformations and a group of healthy children less than one year of age. The parameters studied were prealbumin, retinol-binding protein and the fat-soluble vitamins A and E. There were no significant differences between the groups in the plasma levels of the proteins or vitamin E. Vitamin A levels in newborn infants with myelomeningocele were found to be significantly lower compared to both the other groups. PMID- 1420070 TI - Long-term results after partial and unilateral nephrectomy in childhood. AB - In a clinical follow-up, 47 patients after unilateral or partial nephrectomy were examined. The average age at operation was 5.8 years (range 3 days-17.1 years), the average follow-up period after surgery was 11.9 years (range 8.2-18.3 years). Main indications for surgery were hydronephrosis (n = 27), other congenital malformations (n = 6) and neoplasia (n = 9). In one patient, we found hypertension, two patients presented with moderately diminished creatinine clearance, two further patients suffered from unilateral hydronephrosis after partial nephrectomy. We found by ultrasonography marked compensatory hypertrophy in cases of solitary kidneys (225.6 +/- 49.3%) as well as contralateral kidneys after partial nephrectomy (158.7 +/- 55.6%). PMID- 1420068 TI - Severe lower tracheal stenosis in infancy. AB - 16 infants with severe distal tracheal stenosis (TS) seen from 1978-1988 are reviewed. Diagnosis was established by endoscopy and confirmed by radiographic methods, including magnetic resonance imaging (MRI) in three cases. Types of TS ranged from segmental stenosis to complex lesions involving the carina and bronchi. Associated vascular anomalies were found in nine patients (56%). All patients needed long-term intubation or a tracheostomy (seven cases) for stenting of the airway. Patients with congenital TS (CTS) were treated by tracheal resection (two survivors), dilatation (one survivor, two non-survivors), or observation (two non-survivors). Patients with pulmonary artery sling (PAS) were treated by division of the vascular sling (three survivors, one non-survivor), or combined vascular and tracheal surgery (one non-survivor). One patient with dilated pulmonary arteries compressing both main bronchi died in spite of oxygen therapy. Two cases of compression by an anomalous aorta were managed with dilatation (one survivor, one non-survivor). One patient with a severe stricture after a tracheal resection was successfully treated by dilatation. The overall mortality was 50%. We conclude that 1. endoscopic examination of the tracheobronchial tree and thorough evaluation of associated anomalies is mandatory in symptomatic patients; 2. if indicated surgical correction is the treatment of choice for tracheal stenosis; 3. dilatation and stenting of the stenosis are invaluable tools in the management of these infants. PMID- 1420072 TI - 20 years of functional reconstructive surgery in bladder exstrophy--balance 10 years after a preliminary report. AB - This is an update of a consecutive series of 19 patients with bladder exstrophy presented as a preliminary report 10 years ago with a follow-up of 6 years. The average time of follow-up now is 14 years. In difference to the former report several additional procedures have been performed in most patients. 3 early "good" patients stay "good and continent". Only 3 out of 5 patients categorized as "fair" are now "good and continent" and only one without further intervention. 3 out of 6 patients who were classified as "poor" are now diverted. The overall rate of secondary diversions is 40% including 2 patients with ureterosigmoidostomies. All patients have normal renal function and normal blood pressures. These results show that an early "good" result generally remains "good" but additional surgery may be warranted. The initially "fair" results usually necessitate a secondary procedure, e.g. augmentation cystoplasty or/and bladder neck tightening to show an improvement. Patients with early "poor" results unfortunately remain "poor" and have a great chance to get diverted. PMID- 1420071 TI - Predictability of duration and severity of congenital hydronephrosis as a cause of smooth muscle deterioration in pyelo-ureteral junction obstruction. AB - Between 1989 and 1990, 31 new unilateral PUJO, prenatally diagnosed (16th-37th week of gestational age), underwent pyeloplasty between 19 and 105 days of age. The correlation between severity (V) (volume of hydronephrotic kidney) and duration (dT) of congenital hydronephrosis from its first detection in utero to surgery and histological findings were prospectively evaluated in this series. A dT longer than 70 days and a V larger than 50 ml., were considered as predictable for hypotrophy with fibrosis of the upper urinary tract smooth musculature. In conclusion, time seems to play an important role in the increase of the volume of the obstructed urinary tract to the extent of a large-scale hydronephrosis. PMID- 1420073 TI - Hyperplastic callus formation in osteogenesis imperfecta. AB - Osteogenesis imperfecta, an inherited disorder of connective tissues, affects roughly (OI) 4000 people in Germany (11). The main clinical symptoms are fragile bones, progressing skeletal deformities, generalized osteoporosis and short stature. Incidentally, the clinical manifestations can range from perinatal lethal forms to phenotypical normal adults. In many instances the underlying causes of the disease are mutations in gene coding for collagen I, the predominant protein in most connective tissues. Fracture healing is usually not impaired, although in a unique group of OI-patients, a tumor-like hyperplastic callus occurs with excessive deposition of extracellular matrix constituents. Biochemical analysis of the callus is reminiscent of bone from early stages of human development and normal fracture healing (e.g. collagen type composition, degree of posttranslational modification). This underlines that, besides collagen mutations, the regulation of collagen synthesis and their posttranslational processing might be disturbed in patients with hyperplastic callus formation. PMID- 1420074 TI - Does fibrin glue cause foreign body reactions? AB - The study was performed in 20 Wistar rats. Approximately 4 mm perforations were created in the left colon of ten rats to which fibrin glue was applied (Group D). The control group had the same injury without any therapeutic or surgical measures (Group K). Of the 20 rats in both groups none died during the postoperative period. All animals sacrificed on the 11th postoperative day. All ten rats of Group D displayed inflammatory foreign body reactions. The control group showed no such reaction. PMID- 1420075 TI - Manometric evaluation of children with chronic constipation using a suction stimulating electrode. AB - Thirteen children with chronic constipation (8 males and 5 females, aged 1 month to 9 years) were evaluated manometrically. A suction-stimulating electrode was used to induce the rectoanal reflex electrically so as to examine the threshold voltage and latency of this reflex. The rectoanal reflex was induced in all patients by balloon dilatation of the rectum. However, electrical stimulation of the rectal mucosa triggered a reflex in only nine of them and the threshold voltage and latency was 22.2 +/- 3.6 volts (mean +/- SD, n = 9) and 2.04 +/- 0.38 seconds (n = 9), respectively. Hence, it is suggested that a suction-stimulating electrode is a useful supportive tool in manometric anorectal studies, and that disturbances in the rectal nervous system might be one of the causative factors in chronic constipation in childhood. PMID- 1420076 TI - Rupture of the duodenum with avulsion of the papilla of Vater due to blunt trauma in a child, and review of the literature. AB - Duodenal rupture with avulsion of the papilla of Vater is an uncommon injury due to blunt abdominal trauma in children. This report describes a 9-year-old boy who sustained this injury and was treated successfully two days delayed by a Roux-en Y choledocho-pancreaticojejunostomy and temporary implantation of a zipper for abdominal wall closure. The rarity of this complex injury and its initial presentation as a posttraumatic pancreatitis warrant its description. A review of the literature, modes of diagnosis and surgical technique for repair are described. PMID- 1420077 TI - Acute acalculous cholecystitis caused by Salmonella typhi in a 6-year-old child. AB - A rare case of acute acalculous cholecystitis caused by Salmonella typhi in a 6 year-old child is presented. The clinical signs were fulminant, with diffuse peritonitis being suspected. Cholecystostomy and i.v. ceftriaxone proved efficacious and the girl was discharged in less than two weeks. The appropriate literature is reviewed. PMID- 1420078 TI - Penile dorsal angulation in a child without epispadias. AB - This is a report on a 5-year-old boy with dorsal penile angulation without epispadias. The surgical correction is described. PMID- 1420079 TI - Polyorchidism: a case report and review of the literature. AB - We report on a case of polyorchidism associated with left-sided inguinal hernia and hydrocele. Biopsies of both testes revealed normal histological pattern. After the hernia repair and hydrocelectomy both testes were left at their original places in the scrotum and fixed. Polyorchidism and its management are discussed briefly. PMID- 1420081 TI - Reconstruction of the perineal body after recurrence of a recto-perineal fistula in an intermediate type of anorectal malformation in a young woman. AB - The appearance of a recto-perineal fistula post-operatively in an intermediate type of anorectal malformation is rare. It always gives rise to incontinence. However, the closure of this fistula is particularly difficult since recurrence is frequent. The following case report concerns a patient who after several unsuccessful attempts to close the fistula, had a local rotation flap which permitted good healing and a beneficial effect on continence thanks to a good reconstruction of the perineal body. PMID- 1420080 TI - Thermography in a child with varicocele. AB - A 12-year-old boy with a left-sided varicocele (Grade 3) was assessed preoperatively and followed postoperatively by computer-assisted infrared thermography. The temperature of the left scrotum was 35.4 degrees C before surgery which was 4 degrees C higher than that of the right scrotum. After ligation of the left internal spermatic vein and removal of the varicocele, scrotal thermograms 39 days and 12 months after operation were normal. Therefore, it seems that thermography is very valuable in the evaluation of testicular function in children with varicocele, in whom semen analysis is impossible. PMID- 1420082 TI - Further characterization of the acetyl LDL (scavenger) receptor expressed by rabbit smooth muscle cells and fibroblasts. AB - We have previously demonstrated that the acetyl low density lipoprotein (LDL), or scavenger, receptor is expressed by rabbit smooth muscle cells (SMCs) and fibroblasts. Moreover, receptor activity in rabbit fibroblasts was regulated over a wide range by preincubating the cells with secretion products from human platelets or with phorbol esters. The current studies were undertaken to examine the regulation of receptor expression in rabbit SMCs, to characterize further the receptor expressed by rabbit SMCs and fibroblasts, and to determine whether incubating these cells with chemically modified lipoproteins would lead to foam cell formation. Receptor activity was increased fivefold in rabbit SMCs by preincubation with platelet secretion products and nine- to 20-fold by preincubation with phorbol esters or mezerein, a non-phorbol activator of protein kinase C. The phorbol ester-induced increase in receptor activity was due to an increased mass of scavenger receptor as determined by both ligand blots and immunoblots of membrane proteins from these cells. The immunoblotting studies suggest that the SMC scavenger receptor activity is due to type I or type II scavenger receptors. The scavenger receptor expressed by phorbol ester-treated rabbit SMCs and fibroblasts bound chemically modified LDL with an order-of magnitude higher affinity (Kd 5.1 x 10(-10) M) than did the scavenger receptor expressed by mouse peritoneal macrophages (Kd 4.1 x 10(-9) M), whereas rabbit macrophages bound chemically modified LDL with intermediate affinity (Kd 1.0 x 10(-9) M). Both the phorbol ester-stimulated rabbit fibroblasts and SMCs expressed 10-30% as many receptors per cell as did mouse peritoneal macrophages. Consistent with the difference in the number of receptors, uptake of the chemically modified LDL at 37 degrees C by SMCs led to approximately 25% as much lysosomal degradation and stimulation of cholesterol esterification as in mouse peritoneal macrophages. Incubation of phorbol ester-treated rabbit fibroblasts or SMCs with chemically modified LDL (50 micrograms/ml) for 24 or 48 hours, respectively, resulted in a threefold increase in total cholesterol and a 15-fold increase in cholesteryl ester within the cells. These studies suggest that the scavenger receptor-mediated uptake of modified lipoproteins may contribute to the formation of SMC foam cells in atherosclerotic lesions. PMID- 1420083 TI - Experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. Localization, compensatory enlargement, and the sparing effect of lowered heart rate. AB - We have characterized plaque localization, the extent of compensatory artery enlargement, and the effect of heart rate in experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. We altered heart rate by sino atrial node ablation (SNA) and then fed the animals an atherogenic diet for 6 months. Heart rate was measured at four time points by 24-hour telemetry. Of nine animals with SNA, heart rate was reduced significantly in six (from 148 +/- 11 to 103 +/- 20 beats/min, p < 0.001) and was unchanged in three. Sham-operated monkeys had no significant change in heart rate. On the basis of comparison with the preoperative mean for all 17 animals (136 +/- 22 beats/min), animals were separated into a low-heart-rate (LHR) group (111 +/- 16 beats/min, n = 12) and a high-heart-rate (HHR) group (150 +/- 16 beats/min, n = 5). Blood pressure, serum cholesterol level, and body weight did not differ for the two groups. As in the human, plaques formed predominantly in the proximal portion of the internal carotid artery at the lateral wall opposite the flow divider. Plaque cross sectional area increased progressively from the relatively uninvolved, adjacent common carotid artery to the mid-sinus region of the internal carotid artery and decreased from the mid-sinus region to the internal carotid artery beyond the sinus. Plaque distribution was the same for the LHR and HHR groups, but lesion area and percent stenosis were greater for the HHR group than for the LHR animals (2.01 +/- 1.19 compared with 0.76 +/- 0.42 mm2 for lesion area [p < 0.02] and 30.7 +/- 4.4% compared with 15.2 +/- 7.3% for stenosis [p < 0.002]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420084 TI - Vascular endothelium responds to fluid shear stress gradients. AB - In vitro investigations of the responses of vascular endothelium to fluid shear stress have typically been conducted under conditions where the time-mean shear stress is uniform. In contrast, the in vitro experiments reported here have re created the large gradients in surface fluid shear stress found near arterial branches in vivo; specifically, we have produced a disturbed-flow region that includes both flow separation and reattachment. Near reattachment regions, shear stress is small but its gradient is large. Cells migrate away from this region, predominantly in the downstream direction. Those that remain divide at a rate that is high compared with that of cells subjected to uniform shear. We speculate that large shear stress gradients can induce morphological and functional changes in the endothelium in regions of disturbed flow in vivo and thus may contribute to the formation of atherosclerotic lesions. PMID- 1420085 TI - Monoclonal antibodies against LDL further enhance macrophage uptake of LDL aggregates. AB - Self-aggregates of low density lipoprotein (LDL) are taken up and degraded more rapidly by macrophages than is native LDL. That enhanced uptake is attributable in part to phagocytosis via the LDL receptor pathway. However, arterial macrophages appear to express little LDL receptor activity. The present studies demonstrate an alternative mechanism by which LDL aggregates could contribute to foam cell formation. This could occur by the formation of large immune complexes that are taken up by macrophages via the Fc receptor. When immune complexes were formed with native, soluble LDL and MB47, a monoclonal antibody specific to the apoprotein B domain recognized by the LDL receptor, the subsequent uptake and degradation of the LDL by macrophages were inhibited 50-80% compared with native LDL alone. In contrast, when aggregated LDL was bound to MB47 at a similar molar ratio, the subsequent degradation of the insoluble immune complexes was two- to fivefold greater than that of aggregated LDL alone. The enhanced uptake was abolished when Fab or F(ab')2 fragments of MB47 were substituted for the intact antibody, indicating that the increased uptake was via the Fc receptor pathway. Furthermore, the uptake of the immune complexes of aggregated LDL was reduced by competition for the Fc receptor with heat-aggregated immunoglobulin. There was also an increase in the rate of cellular cholesterol esterification and an increase in macrophage cholesteryl ester mass. Since aggregates of LDL as well as autoantibodies against modified LDL have been demonstrated in atherosclerotic lesions, it is possible that immune complexes of aggregates of modified LDL may be generated in the intima.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420086 TI - Time course and cellular characteristics of the iliac artery response to acute balloon injury. An angiographic, morphometric, and immunocytochemical analysis in the cholesterol-fed New Zealand white rabbit. AB - Evaluation of the response of the arterial vessel wall to acute arterial injury in experimental models has taken on substantial importance because of an increasing interest in angioplasty treatment of human atherosclerotic lesions. In this study, the response of normal arterial vessels to acute balloon injury was studied in 45 iliac artery segments from 24 New Zealand White rabbits fed a 2% cholesterol diet. At specified time points between 1 and 41 days after the initial balloon pullback injury, the iliac arteries were analyzed by angiographic, morphometric, and immunocytochemical techniques. Angiographic measurements indicated progressive compromise of the iliac artery lumen with increasing duration of time from injury. Morphometric measurements showed that intimal area increased from 0.004 +/- 0.01 mm2 3 days after injury to 1.15 +/- 0.30 mm2 34-41 days after injury. Cell line-specific immunocytochemical analysis identified the macrophage as a prominent component of the earliest intimal cellular infiltrate. Smooth muscle cells appeared within the intima 7-9 days after injury. As the intima increased in area, macrophages predominated along the internal elastic lamina aspect of the intimal lesion while smooth muscle cells occupied the portion of the intima adjacent to the lumen. In summary, retrograde balloon pullback injury followed by cholesterol feeding results in progressive arterial luminal narrowing due to a progressively enlarging intimal cellular infiltrate. The temporal and spatial contributions of smooth muscle cell and macrophage components of the developing intimal cellular infiltrate have been characterized. PMID- 1420087 TI - Hepatic ACAT activity in African green monkeys is highly correlated to plasma LDL cholesteryl ester enrichment and coronary artery atherosclerosis. AB - Previous studies and this study of African green monkeys show a strong positive correlation between plasma low density lipoprotein (LDL) size and the extent of coronary artery atherosclerosis (CAA). Increased LDL size was principally due to the accumulation of cholesteryl oleate molecules within the particle core, suggesting that many of these cholesteryl esters were of tissue origin, i.e., from the acyl-coenzyme A:cholesterol acyltransferase (ACAT) reaction instead of the lecithin:cholesterol acyl-transferase (LCAT) reaction. The current study was conducted to test the hypothesis that ACAT in the liver is the source of the increased numbers of cholesteryl oleate molecules in plasma LDL particles that appear to increase the atherogenic potential of LDL. Monkeys were fed diets rich in fat (lard, safflower oil, or fish oil) and cholesterol for 3-6 years before liver perfusion, ACAT assay, and evaluation of CAA. Hepatic ACAT activity was positively correlated with hepatic cholesteryl ester secretion (r = 0.61, p < 0.001), plasma LDL cholesteryl ester content (r = 0.60, p < 0.0001), and the extent of CAA (r = 0.62, p < 0.0001). The number of cholesteryl oleate molecules within LDL increased proportionally with LDL size in each of the diet groups. Hepatic cholesteryl oleate concentration was correlated with the accumulation of cholesteryl oleate in liver perfusate (r = 0.72, p < 0.01) and with plasma LDL cholesterol oleate content (r = 0.73, p < 0.0001). Our interpretation is that these data, obtained in a relevant primate model of CAA, suggest that hepatic ACAT increases the atherogenicity of LDL by augmenting both the secretion by the liver and accumulation in plasma LDL of cholesteryl oleate. PMID- 1420088 TI - Change in LDL particle size is associated with change in plasma triglyceride concentration. AB - Low density lipoprotein (LDL) particle size is inversely associated with plasma triglyceride concentration in cross-sectional analyses. In the present study, changes in the LDL particle size of 227 participants of the Framingham Offspring Study were analyzed longitudinally by nondenaturing gradient gel electrophoresis at two examinations that were separated by 3-4 years. All subjects had triglyceride concentrations < 400 mg/dl at both exams. Using laser scanning densitometry to assess mean LDL particle size, 56% of samples displayed a change in size: 41% had a one-band size change, 13% had a two-band change, and 2% had a three-band change. These changes in size corresponded to a 15% change in pattern type, based on pattern A and B terminology. There was a significant inverse association between change in LDL size and change in triglyceride (p < 0.0001) and glucose (p < 0.004) concentrations, body weight (p < 0.02), and age (p < 0.03). There was also a significant positive association with change in high density lipoprotein (HDL) cholesterol concentration (p < 0.0001). Change in LDL cholesterol concentration, as calculated by use of the Friedewald formula, however, showed no significant association with change in LDL size (p < 0.9). There was also no significant association with change in smoking or blood pressure, but there was a nonsignificant inverse trend associated with alcohol intake (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420089 TI - Cholesterol efflux is defective in macrophages from atherosclerosis-susceptible White Carneau pigeons relative to resistant show racer pigeons. AB - White Carneau (WC) pigeons are susceptible to the development of aortic atherosclerosis, whereas Show Racer (SR) pigeons are resistant, even though there are no differences in the known risk factors, including plasma cholesterol levels, lipoproteins, blood pressure, etc. Although this suggests that the difference in atherosclerosis susceptibility between WC and SR pigeons may be mediated at the level of the arterial wall, we have yet to identify a mechanism that can account for this difference. In pigeons as in other species (including humans), macrophages play a major role in the pathogenesis of atherosclerosis. Pigeon macrophages have multiple mechanisms for the uptake of lipoproteins and the accumulation of cholesteryl esters. To date, however, no differences in lipoprotein uptake between macrophages of WC and SR pigeons have been identified that could explain the difference in atherosclerosis susceptibility. In the present study we explored the alternative hypothesis that there are differences in the rate of cholesteryl ester clearance from peritoneal macrophages isolated from the two breeds of pigeons. Cholesterol efflux studies were conducted with elicited pigeon peritoneal macrophages that were loaded with cholesteryl ester either in vitro by incubation with rabbit beta-very low density lipoprotein or in vivo by isolation of macrophages from birds fed a cholesterol-containing diet. Using these techniques we were able to load WC and SR macrophages consistently with cholesteryl esters to levels typical of arterial foam cells (150-1,150 micrograms/mg cell protein). Under these cholesterol loading conditions there was no net efflux of cholesterol from either WC or SR macrophages when incubated for up to 24 hours in the presence of pigeon or human high density lipoprotein (HDL), fetal bovine serum, or lipoprotein-deficient serum. Under the same conditions, efflux of cholesterol from mouse peritoneal macrophages was stimulated by human and pigeon HDL. Despite the inability of HDL, lipoprotein-deficient serum, or fetal bovine serum to promote net cholesterol efflux, apoprotein (apo) HDL/phosphatidylcholine (PC) vesicles stimulated cholesteryl ester clearance from both WC and SR pigeon macrophages but at a significantly slower rate from WC pigeon macrophages. When incubated in the presence of excess apoHDL/PC (400 micrograms/ml), the rate of depletion of cellular cholesteryl esters was log linear for at least 48 hours. WC macrophages cleared an average of only 9% of their cholesteryl esters in 24 hours when incubated with excess apoHDL/PC, whereas SR macrophages reduced their cholesteryl ester content by an average of 42%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1420090 TI - Long-term nicotine exposure increases aortic endothelial cell death and enhances transendothelial macromolecular transport in rats. AB - Repeated endothelial cell injury has been suggested as an initiating factor in atherogenesis. Dying or dead endothelial cells have been shown to make significant contributions to the local enhancement of transendothelial macromolecular transport. Since cigarette smoking is one of the major risk factors for atherosclerosis, we examined the hypothesis that smoking accelerates atherogenesis by increasing the frequency of endothelial cell death and hence transendothelial macromolecular transport. Sixteen male Sprague-Dawley rats were given nicotine at a weight-adjusted dose of 5 mg/kg body wt per day in their drinking water over a period of 6 weeks. A group of 16 age-matched male Sprague Dawley rats not exposed to nicotine and maintained over the same time period served as the control group. In en face preparations of thoracic aorta, immunoglobulin G-containing dying or dead endothelial cells were identified by the indirect immunoperoxidase method, and endothelial leakage to Evans blue albumin (EBA) complexes (5 minutes after intravenous injection) was visualized by fluorescence microscopy. The results showed that in nicotine-treated rats, 51% of dead endothelial cells were associated with EBA leakage, which was responsible for 57% of total EBA leaky foci. Both the frequency of endothelial cell death (0.94 +/- 0.11% versus 0.40 +/- 0.04%, p < 0.0001 by two-tailed, unpaired Student's t test) and the number density of EBA leaky foci (6.45 +/- 1.23/mm2 versus 3.30 +/- 0.49/mm2, p < 0.05 by two-tailed, unpaired t test) were significantly greater in nicotine-treated rats than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420092 TI - Mast cell-mediated inhibition of reverse cholesterol transport. AB - Net cholesterol efflux from cholesterol-loaded macrophages, i.e., foam cells, was induced by incubating the foam cells with high density lipoprotein3 (HDL3). However, when the incubation system included rat serosal mast cells stimulated to trigger exocytosis of their cytoplasmic secretory granules, the ability of HDL3 to induce cholesterol efflux was largely lost. This loss was found to be due to the proteolytic action of chymase, the neutral protease of the granules, which degraded the apolipoproteins of HDL3, so rendering them unable to mediate cholesterol efflux from the foam cells. The observation defines a novel cell dependent mechanism that blocks the initial steps of reverse cholesterol transport and suggests a role for mast cell chymase in cellular accumulation of cholesterol, an early stage in atherogenesis. PMID- 1420091 TI - Effect of endothelial integrity, transmural pressure, and time on the intimal medial uptake of serum 125I-albumin and 125I-LDL in an in vitro porcine arterial organ-support system. AB - This report describes a new in vitro, metabolically supported, Sinclair Research Farm minipig aortic preparation in which the intimal-medial uptakes (M, mg.cm-2 of intimal surface) of porcine 125I-albumin and normocholesterolemic (nonoxidized) porcine 125I-low density lipoprotein (LDL) from a stirred, autogenous serum (containing a 125I-protein concentration of c0, mg.cm-3 at 37 degrees C and pH 7.4) were studied as functions of transmural pressure (0 < or = P < or = 150 mm Hg), time (30 < or = t < or = 120 minutes), and endothelial integrity. The following new observations were made: 1) The normalized transendothelial uptakes (M/c0, cm) of both albumin and LDL across normal intact aortic endothelial surfaces were insensitive to P. This indicated that these macromolecular solutes were not readily convected across the normal aortic endothelial surface despite increasing P. 2) However, the associated transendothelial M/c0 versus t relations for the normal intact surfaces were shown to increase monotonically with t in a manner consistent with a simple diffusive transport across a large surface barrier into the subjacent media, either with (Cases 2A and 2B) or without (Case 1) an associated transmural water convection. 3) The shapes of these temporal M/c0 curves of albumin and LDL were virtually the same; however, the magnitude of the albumin M/c0 curve was about sevenfold greater than that of LDL. 4) The M/c0 across the injured endothelial surface (Case 2C) not only increased monotonically with t but also increased significantly with P, indicating that in the absence of a normal endothelial surface, a very large convective component was added to the transport processes across the exposed aortic endothelial basement membrane and internal elastica. We conclude that: 1) the normal porcine aortic endothelial surface can provide a virtually complete barrier to the transendothelial convective transport of both albumin and LDL, 2) the diffusive barrier of the normal endothelial surface to LDL was sevenfold greater than that to albumin, 3) loss of the endothelial cell layer was associated with a threefold increase in the (P = 0) diffusive intimal medial uptake of serum albumin in contrast to an eightfold increase in the pressurized (P = 150 mm Hg) combined diffusive-convective intimal-medial albumin uptake in the same vessel. PMID- 1420093 TI - Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. AB - The status of fasting triglycerides as a risk factor for coronary artery disease (CAD) has been considered weak because in multivariate analyses, triglycerides tend to be eliminated by high density lipoprotein (HDL) cholesterol. To further evaluate the role of triglycerides in CAD, we employed postprandial lipemia as a more informative means of characterizing triglyceride metabolism. In 61 male subjects with severe CAD and 40 control subjects without CAD as verified by angiography, we measured cholesterol; triglycerides; HDL cholesterol; HDL2 cholesterol; and apolipoproteins A-I, A-II, and B in fasting plasma and triglycerides before and 2, 4, 6, and 8 hours after a standardized test meal. Both the maximal triglyceride increase and the magnitude of postprandial lipemia (area under the triglyceride curve over 8 hours after the meal) were higher in cases than in control subjects. Single postprandial triglyceride levels 6 and 8 hours after the meal were highly discriminatory (p < 0.001), and by logistic regression analysis displayed an accuracy of 68% in predicting the presence or absence of CAD. In this respect, accuracy was higher than that of HDL2 cholesterol (64%) and equal to that of apolipoprotein B (68%), the most discriminatory fasting parameter. Multivariate logistic-regression analysis was performed to reduce the number of risk factors to those that were statistically independent. This statistical procedure selected postprandial but not fasting triglycerides into the most accurate multivariate model, which also contained the accepted risk factors HDL2 cholesterol, apolipoprotein B, and age. This model classified 82% of subjects correctly. We conclude that triglycerides are independent predictors of CAD in multivariate analyses including HDL cholesterol, provided that a challenge test of triglyceride metabolism such as postprandial lipemia is used. The study suggests that the metabolism of triglycerides is a critical determinant of cholesterol metabolic routing. The findings support the concept that the negative association between HDL cholesterol levels and CAD actually originates in part from a positive relation between CAD and plasma triglycerides, as ascertained in the postprandial state. PMID- 1420094 TI - Serum Lp(a) as a discriminant marker of early atherosclerotic plaque at three extracoronary sites in hypercholesterolemic men. The PCVMETRA Group. AB - To investigate the role of lipoprotein (a) (Lp[a]) as an atherogenic condition related to hypercholesterolemia, we studied the serum concentration of Lp(a) as measured by immunonephelometry in relation to the presence of asymptomatic echographic plaques in the peripheral arteries of 103 untreated hypercholesterolemic, normotensive, middle-aged men. Plaque was found at carotid, aortic, and femoral sites in 36%, 51%, and 53% of subjects, respectively. The Lp(a) level was higher in the group with carotid plaques than in the group without (0.29 +/- 0.20 versus 0.17 +/- 0.14 g/l, p < 0.01), not significantly higher in the group with aortics plaque than in the group without (0.24 +/- 0.19 versus 0.19 +/- 0.16 g/l), and not different between groups with and without femoral plaques (0.21 +/- 0.18 versus 0.22 +/- 0.17 g/l). A logistic regression analysis confirmed that Lp(a) was associated with carotid plaques (p = 0.004), independent of other risk factors. However, in patients with low density lipoprotein cholesterol values above the group median value (4.7 mmol/l), Lp(a) was associated not only with carotid plaques (p < 0.01) but also with aortic plaques (p < 0.05), as well as with the number of diseased sites (p = 0.02). In contrast, in patients with low density lipoprotein cholesterol levels below or equal to 4.7 mmol/l, Lp(a) only remained associated with carotid plaques (p < 0.05). Thus, in symptom-free, hypercholesterolemic men, early atherosclerosis was influenced by serum Lp(a), particularly in the carotid arteries, as well as by the presence of a higher level of low density lipoprotein cholesterol. PMID- 1420096 TI - Etoposide treatment suppresses atherosclerotic plaque development in cholesterol fed rabbits. AB - To study the mechanisms by which monocytes/macrophages and smooth muscle cells contribute to atherosclerotic lesions, we studied atherosclerotic plaque formation in cholesterol-fed rabbits treated with etoposide, a drug that has been shown to have several effects that could interfere with the proposed interactions between these two cell types (M.W. Aarnoudes et al, Virchows Arch B 1984;47:211 216 and M. Rozencweig et al, Cancer 1977;40:334-342). Our results show that long term etoposide treatment of New Zealand White rabbits maintained on a high cholesterol diet decreases the extent of fatty streak formation in the aortic intima. Moreover, the plaques formed in the presence of etoposide are thinner and at least focally have less fibrous tissue and fewer smooth muscle cell-derived foam cells than do plaques in control rabbits. These effects are independent of the extent of the diet-induced hyperlipemia or an effect of etoposide on blood cell count and may be related to the inhibition of intimal cell proliferation by etoposide. PMID- 1420095 TI - LDL binding sites on platelets differ from the "classical" receptor of nucleated cells. AB - Washed human platelets bound radioiodinated low density lipoprotein (125I-LDL) to a class of saturable binding sites; they numbered 1,348 +/- 126 per platelet, and the dissociation constant (KD) was 50.7 +/- 9 nM. 125I-LDL binding to platelets was reversible, and apparent equilibrium was attained within 25 minutes at 22 degrees C and was characterized by forward and reverse rate constants of 1.47 x 10(4) x sec-1 x M-1 and 8 x 10(-4) x sec-1 x M-1, respectively. Such binding was largely unaltered by temperature, divalent ions, and chelating agents. In addition, neither did receptor regulation (up or down) occur when platelets were loaded with cholesterol, nor did prostaglandin E1 (PGE1) increase the binding of 125I-LDL to platelets. On the other hand, the specificity of LDL binding was not typical of the LDL receptor of nucleated cells. Lipoproteins competed for the occupancy of LDL binding sites in platelets with the following order of potency: very low density >> intermediate density > high density subfraction 2. High density lipoprotein subfraction 3, heparin, and PGE1 had no effect on this binding. 125I-LDL binding to lymphocytes and fibroblasts and proteolytic degradation of 125I-LDL by lymphocytes was inhibited by the monoclonal antibody IgG-C7 directed against the LDL receptor to 88%, 85%, and 85% (p < 0.001), respectively. However, with this monoclonal antibody, a blocking effect on neither 125I-LDL binding to platelets nor on LDL-enhanced platelet aggregation induced by ADP and collagen was found. Moreover, we confirmed the existence of LDL binding in platelets from patients with familial hypercholesterolemia. Our results indicate that human platelets bind LDL by saturable sites, which clearly differ from the "classical" LDL receptor in their binding properties, absence of receptor regulation, presence in platelets of familial hypercholesterolemia patients, and the lack of a blocking effect of IgG-C7 on LDL binding and LDL biological activity. PMID- 1420098 TI - A longitudinal study of the effects on the oral mucosa of treatment for acute childhood leukaemia. AB - A longitudinal study was undertaken of the effect of therapy on the oral mucosa of 12 children with acute leukaemia. The major oral problem was ulceration, which was associated with neutrophil counts of less than 1.0 x 10(9)/l. Candida carriage rates were consistently high in patients with or without oral candidosis. Salivary flow was not significantly different between leukaemic children and the control group. PMID- 1420097 TI - Dentigerous cysts involving permanent incisors: four case reports. AB - Four cases of dentigerous cysts involving permanent incisors are reported. In each case the primary predecessor had been traumatized, was discoloured and suspected of being non-vital. Epithelial proliferation of the follicular tissues induced by chronic periapical inflammation of the predecessors is suggested as the most likely pathogenesis of cystic transformation in these cases. Regular radiographic review of discoloured primary incisors is recommended. PMID- 1420100 TI - Dental caries in 12-year-old children in Salford, UK: changes over 28 years. AB - A sample of 111 12-year-old children in Salford, UK was examined in 1988, and the findings compared with those of a survey carried out in 1960 of 12-year-old children in the same city. Between 1960 and 1988, the mean DMFT of the boys fell from 6.04 to 2.34 and that of the girls from 6.54 to 3.40. All types of teeth were affected by caries in 1960 but in 1988 none of the canines and mandibular lateral incisors were affected. In 1960 the permanent first molars contributed 57% of the boys' and 54% of the girls' total DMFT while in 1988 they contributed 87% of the boys' and 73% of the girls' DMFT. Jackson's Treatment Index showed that the dental services were making a greater impact in 1988; for the boys it rose from 29.5 to 63.2 and for the girls from 27.8 to 62.3. PMID- 1420099 TI - Dental health and salivary Streptococcus mutans levels in a group of children with heart defects. AB - One-hundred children aged 2-16 years who were attending the Outpatients Department of the Yorkshire Regional Cardiac Centre were examined for dental caries, gingivitis, plaque and calculus. A control group of 100 children was also examined. A saliva sample was taken from each child in the study group to assess the level of Streptococcus mutans colonization. Comparing study and control groups, dental caries experience (dmft) was significantly higher only in the primary teeth of 5-9-year-old children in the study group, and there were no significant differences in gingivitis, plaque or calculus. The S. mutans count was found to be positively correlated to the number of decayed teeth in the study group. PMID- 1420101 TI - Flow rate and chemistry of parotid saliva related to dental caries and gingivitis in patients with thalassaemia major. AB - Twenty-one child patients with thalassaemic major (TM) and 83 healthy control children were examined for dental caries and gingivitis. Stimulated parotid gland secretions were collected from each child. Parotid saliva flow rate was measured and the saliva samples were tested for calcium, phosphorus, potassium, sodium, urea, lysozyme and immunoglobulin levels (IgA, IgG, IgM). The results showed that dental caries experience was significantly higher in the TM group. Parotid saliva flow rates in TM patients were not significantly different from those in the healthy controls. However, the median saliva concentrations of phosphorus and IgA were significantly lower in the patients than in the controls. The concentration of lysozyme was also lower in the TM group, but the difference was not statistically significant. The findings could provide an explanation for the higher dental caries experience and gingivitis observed in the TM group. PMID- 1420102 TI - Dental management of a child with EEC syndrome. AB - The EEC syndrome is a condition characterized by ectrodactyly, ectodermal dysplasia and clefting of the lip and/or palate. Here we report a case of a boy with the EEC syndrome. The clinical and radiologic aspects of this condition, as well as the dental treatment, are reviewed. PMID- 1420103 TI - [Significance of the so-called symptomless periods of disease]. AB - Considerable change has occurred to nosology due to the advent of electron microscopy and its use in investigations of pathological processes. These investigations have shown that morphological alterations under the impact of pathogenic factors may persist for extended periods of time without any clinical manifestation due to soon effectiveness of mechanisms of compensation in the form of regeneration and hyperplasia of cells and intracellular ultrastructures (intracellular regeneration). Clinical symptoms will not grow manifest until regeneration and hyperplasia are not capable any more of compensation for tissue lesions that have resulted from dystrophy and necrosis. This is likely to offer an explanation for delay of treatment, when a patient will not see a physician until the disease has become incurable. It is the established purpose of early diagnosis to detect structural alterations in organs during the asymptomatic preclinical period, that is before the disease has reached an advanced stage. The idea of "primary existent functional and secondarily added morphological alterations" is just as erroneous as that of the existence of "purely functional diseases". Such outdated concepts used to be based on underestimation of compensatory reactions of the organism and the enormous role played by them in the development and outcome of pathological processes. PMID- 1420104 TI - [Pathology of the placenta. XI. Feto-fetal transfusion syndrome]. AB - An account is given in this part of the series of placental alterations in the foeto-foetal transfusion syndrome of monochorial twin pregnancies. Arteriovenous or less often arterio-arterial anastomoses between the two parts of the placenta were found to be conditions for such foeto-foetal transfusion. Blood is discharged on the foetal side from one twin to the other, with one of the twins being adversely affected in growth and general development (donor), which may be as bad as acardia in case of very early onset of transfusion. The other twin (recipient) will undergo better development but will as well be impaired by cardiac hypertrophy and other organic lesions due to excessive inflow of blood. The placenta of the donor--quite often meeting intra-uterine death--usually is smaller than that of the recipient. It is severely anaemic and, additionally, may be of inadequate maturity. The placenta of the recipient may exhibit strongly pronounced hyperaemia, up to A and B angiomatosis. The author describes two of his own cases, with reference being made to morphological findings. PMID- 1420105 TI - [Pathomorphology of experimental Candida mycosis]. AB - An account is given in this paper of evaluated results obtained from over 30 years of research on the pathogenesis and morphology of experimental candidiasis. No success has so far been recorded from efforts to set up a fully valid animal experimental model of all forms of candidiasis in man. Models so far can be successfully constructed only for certain links in the process of infection. Particular importance, in this context, should be attributed to effects on the organism which would cause improvement or reduction of specific and unspecific resistance. Critical analysis of results obtained from differently conceptualized experiments has contributed to comprehensive understanding of the morphogenesis of opportunistic candida infections in man. Models established in the wake of animal experiments have provided a basis for formulation of principles of a combined candidiasis therapy, using both antibiotics and immunomodulators. PMID- 1420107 TI - Comparative lectinhistochemical studies on paraffin- and glycol methacrylate embedded CNS tissue specimens from AIDS autopsies. Mistletoe lectin I (ML I) as cell-marker. AB - Brain tissue and spinal cord tissue from 12 patients who had died of AIDS was fixed in neutral formalin; then after the embedment of some of it in paraffin and some of it in glycol methacrylate, it was analyzed lectinhistochemically with mistletoe lectin I (ML I). Mistletoe lectin (ML I) is a reliable marker for microglia cells and macrophages and for special cell forms (polynuclear giant cells, so-called pericytes) belonging to this cell system. In both the embedding procedures used, the representation of the cells is very clear and subtly differentiated so that the preparations are very well suited to the study of AIDS associated tissue damage in the CNS. Whereas the immunological macrophage markers (CD 68 markers) KPI, PG-M1 produce good results on paraffin-embedded material but are completely useless on material embedded in glycol methacrylate, the cells of the monocyte-macrophage system can be represented very well and reliably after being embedded in glycol methacrylate with mistletoe lectin I (ML I). PMID- 1420106 TI - Analysis of expression of erythropoietin-binding sites in human lung carcinoma by the biotinylated ligand. AB - Recombinant glycosylated erythropoietin (EPO) was biotinylated with biotin aminocaproyl hydrazide via periodate-treated sialic acid moieties and applied to sections of 64 tumors of the lower respiratory tract, comprising 19 primary adenocarcinomas, 19 epidermoid carcinomas, 13 large cell anaplastic carcinomas, 11 small cell lung carcinomas, 11 intrapulmonary metastases, 1 mesothelioma and 1 lymphocytic interstitial pneumonia. The formalin-fixed, paraffin-embedded specimens were incubated with labelled EPO at room temperature and a concentration of 10 micrograms/ml for 60 min. The expression of the EPO-binding sites was visualized by the ABC technique. All of the analyzed large cell anaplastic carcinomas and the majority of the epidermoid carcinoma (89%), adenocarcinoma (79%), and metastases (82%) displayed binding capacities for EPO. Five out of the eleven small cell lung carcinomas, the analyzed mesothelioma and lymphocytic interstitial pneumonia revealed definite staining, too. Binding sites could, in addition, be seen in air dried, non-fixed, acetone-fixed, and ether ethanol-fixed cytological specimens. The data indicate that the expression of binding sites with specificity for EPO can be frequently seen in human bronchial malignancies. PMID- 1420108 TI - [Ultrastructure of amitosis and mitosis of the liver]. AB - Thousands of liver cells of several ultrastructural investigation programs of our laboratory have been evaluated in respect to amitosis and mitosis. Multiplication of hepatocytes by amitosis and mitosis often leads to bi-, tri- and multinucleated cells. No striking ultrastructural changes have been observed in the hepatocytes of human and animal livers. There are no indications of enhanced autophagocytosis or other signs of dedifferentiation. However, non-hepatocytes suffer ultrastructural changes during mitosis: endothelial cells reduce their organelles in number, round up their shape and form microvilli reaching between the microvilli of hepatocytic sinusoidal membrane. Mitotic Kupffer cells contain only small phagosomes and are separated from hepatocytes by endothelial cell processes. PMID- 1420109 TI - Congenital malformations of the respiratory tract. AB - Malformations of the respiratory tract were found in 21 out of 205 foetuses (10%) in whom various congenital malformations had been prenatally detected by ultrasonography and amniocentesis. Pulmonary hypoplasia was the most common of all pulmonary malformations and was established in 17 cases (81%). Lung alobulation was established in two cases (9.5%), and pulmonary cysts were recorded in another two cases in post-mortem examinations. Correlations established between ultrasonographic and pathomorphological findings were not satisfactory as only 29% of all ultrasonographic diagnosis were complete and correct. Hence, much closer cooperation between the pathologist and clinician is essential to all investigations of congenital malformations, in particular to those of complex nature. PMID- 1420110 TI - [Syncytial variant of the nodular sclerosing type of Hodgkin's disease in cervical lymph nodes with simultaneous sarcoidosis-like granulomatosis in the intrathoracic lymph nodes and liver]. AB - A woman aged 31 years had been afflicted with mediastinal lymph node enlargement and hepatopathy for two years. Epithelioid-cell granulomatosis was diagnosed at another institute on the basis of biopsies taken from the liver and thoracic lymph nodes, resulting in the differential diagnosis of sarcoidosis or tuberculosis. Another biopsy was taken from enlarged cervical lymph nodes, after tuberculostatic therapy had remained unsuccessful and had not prevented deterioration of the patient's condition. We diagnosed from that biopsy the syncytial variant of nodular sclerosis of Hodgkin's disease. Immunohistochemically, the tumour cells exhibited positive reactions to antigens CD 15 and CD 30, whereas no evidence was provided to the presence of cytokeratins, lysozyme and S-100 protein. In grading, we associated our case with subtype 2 of nodular sclerosis and clinical stage II. Combined radiotherapy and chemotherapy resulted in complete remission of the tumour disease. Presence of granulomatosis similar to sarcoidosis was confirmed by follow-up examination of the liver and lymph node biopsies which originally had been histopathologically examined at another institute. The question is discussed whether or not this granulomatous reaction reflected an increased immunological defence reaction of the organism to Hodgkin's disease and thus offered an explanation for the unexpected favourable course of the patient's disease. PMID- 1420111 TI - [Aggressive angiomyxoma of the vulva and perineum]. AB - Reported in this paper are two cases of aggressive perineovulvar angiomyxoma. Soft, painless tumours with gelatinous cut surface were detected in either patient, two women aged 32 and 46 years. Histological findings included fibromyxoid stroma with spindle-shaped and stellate cells as well as vascularization in striking abundance. Most of the vessels were thin-walled. There was no plexiform arborization. Strongly atypical nuclei or mitoses or necrotic foci were not recordable. The tumour exhibited infiltrative growth. Tumour cells could be immunohistochemically associated with antibodies against vimentin, whereas negative responses were recorded from antibodies against S-100 protein, factor-VIII-associated protein and pancytokeratin. Aggressive angiomyxoma is a biologically benign neoplasia prone to recurrence and typically localized in soft tissue of the pelvic region. Metastases so far have never been found. Wide local excision has proved to be the optional therapeutic approach. PMID- 1420113 TI - Twelve HLA-DR6-related DRB1 alleles and associated DR, DQ haplotypes in traditional Australians and other populations of Asia-Oceania. AB - The relative distributions of 12 HLA-DR6-related HLA-DRB1 alleles in indigenous populations of Australia, Melanesia, Polynesia, Micronesia, and northern and southern China have been determined by analysis of nucleotide sequence polymorphisms in 364 examples of HLA-DR6 positive chromosomes. Oligonucleotide hybridizations of polymerase chain reaction products of HLA-DQA1, DQB1, DRB1 and DRB3 genes generated 24 HLA-DR6-related haplotypes. The study aimed to determine the regional distribution of DR,DQ haplotypes associated with three novel HLA-DR6 alleles, namely DRB1*1408, 1409, and 1410, known to occur in Australian Aborigines, to gain further insights into the molecular phylogeny of these alleles. DRB1*1408 was the most common HLA-DR6 subtype in Oceania, although it was not detected in Chinese. In Australian Aborigines and Papua New Guinean highlanders, DRB1*1408 was associated with DRB3*0202, while in Polynesians and Micronesians it was associated with DRB3*0101. The different haplotype arrangements, together with the near absence of DRB1*1408 in coastal Melanesians, suggest the possibility that two independent mutations have generated DRB1*1408 in Australia and Oceania. DRB1*1409 and 1410 alleles were confined to Australian Aborigines, while DRB1*1407 was found exclusively in Melanesians; DRB1*1401 was the only HLA-DR6 allele represented in all study populations. The population specific HLA-DR6 alleles and haplotypes have important implications for unrelated bone-marrow donor registries in Australia and Oceania. PMID- 1420112 TI - [Primary intracranial plasma cell granuloma. Report of two cases]. AB - Investigation of biopsies of a suprasellar tumour in a man, 33 years of age, and a supratentorial tumour in a woman, 18 years of age, resulted in histological diagnosis of intracranial plasma cell granuloma, a rare condition. Polyclonality of the plasma cells involved in the process could be verified by immunohistochemical investigation. Chordoma was clinically assumed in the first case and meningioma in the second. Biological behaviour and dubious prognosis are discussed, with reference being made to relevant literature. PMID- 1420114 TI - Diversity in DNA rearrangements and in RNA expressions of immunoglobulin gene on common variable immunodeficiency. AB - Six heterogeneous common variable immunodeficiency (CVID) patients were analysed for germ-line DNA, DNA rearrangements, and RNA expressions of immunoglobulin (Ig) gene by Southern or northern blotting using appropriate probes. We detected no polymorphism in neutrophil DNA hybridized to a C mu and a C gamma probe. In three patients, both serum Ig and Ig-bearing cells were scarcely detected, and by northern hybridization methods, neither mu mRNA, gamma mRNA, alpha mRNA nor kappa mRNA was detected. However, one Epstein-Barr virus-transformed B lymphoblastoid cell line (LCL) of these three patients was different from the germ line in the region of JH, C gamma, and C kappa, and expressed mu mRNA at a higher level. The B cell defects of these three patients lay on the B cell maturation stage similar to X-linked agammaglobulinaemia (XLA). In two others among the six CVID patients, serum IgM and IgM-bearing cells were detected to a certain degree, and by northern hybridization, mu mRNA was detected at a lower level, but neither mu mRNA, alpha mRNA, nor kappa mRNA was detected. One LCL of these two patients could express mu mRNA at the normal level. In the last patient, the serum IgM was normal, serum IgG and IgA were somewhat low, Ig-bearing cells were normal, mu mRNA and kappa mRNA were detected at the normal level, and gamma mRNA and alpha mRNA were detected at a lower level. The defect of this patient affected the class switch stage. These results showed that primary B cell defects in CVID occurred at several B cell differentiation stages which could be classified by expression of the Ig gene, and at the degree of clonal diversity in the B cell repertoire. Furthermore, this study provides support for the idea that the CVID defect is related to a more generalized cellular function, such as regulating the proliferation and/or clonal expansion of cells of the B lymphoid lineage. PMID- 1420115 TI - Nucleotide sequencing of HLA-DQ gene second exons in Chinese homozygous cells. AB - Six HLA class I and class II-homozygous Chinese cell lines with unique HLA-Dw types were studied. Since the majority of HLA class II nucleotide sequence polymorphism is localized within the second exons of the genes, we used the polymerase chain reaction (PCR) to amplify these regions in HLA-DQA and DQB genes and subsequently determined the nucleotide sequences. No unique DQA1 or DQB1 alleles were found. However, a new haplotype of DQA1*0601-DQB1*0301-DRB1*1202 was found in two cells; and DQA1*03011 was found in association with DR9 in another two cells. This indicates that new DR-DQ associations may explain the observed new HLA-Dw types. The DQB2 sequences were identical in all six cells and were identical to a sequence previously reported in a DR6 haplotype. The DQA2 sequences from two clones obtained from two cells differed from each other and from previously reported sequences. The results show that the DQA1 and DQB1 alleles in the Chinese individuals studied are as previously reported in Caucasian populations and as such may be typed by restriction fragment-length polymorphism (RFLP) or PCR-sequence-specific oligonucleotide typing (PCR-SSO) or PCR-RFLP using conventional probe or restriction enzyme sets. PMID- 1420116 TI - Serological and molecular analysis of HLA in Israeli primary sclerosing cholangitis patients. AB - HLA class I and class II were investigated in 15 Israeli primary sclerosing cholangitis patients and compared to healthy controls. None of the well established serological specificities were found to be associated with the disease. HLA-DR52 is serologically defined, but its subtypes DR52a, DR52b, and DR52c cannot be precisely defined by serological means. Therefore, we have used HLA-DNA typing in order to assign the DR52 splits in PSC patients. Genomic DNA was amplified by PCR, dot-blotted and hybridized with sequence specific oligonucleotide probes defining the known HLA-DR52 associated alleles. Only 4 out of the 15 PSC patients tested were found to express DRB3*0101 the allele that encodes DR52a. Of the remaining 11 patients, 9 expressed DRB3*0202 haplotypes, with 2 patients expressing both DRB3*0101 and DRB3*0202, and the remaining 2 patients expressed no DRB3 allele. Our data indicate that there is no apparent association between PSC and the HLA antigens and alleles studied including the alleles of the DRB3 locus in the Israeli population. Thus HLA pheno/genotyping of PSC patients in the Israelis will not be useful for early and/or differential diagnosis of this disease. PMID- 1420118 TI - Frequency of HLA-DPB1 alleles in multiple sclerosis patients from Northern Ireland. AB - Using sequence-specific oligonucleotide probes, no altered distribution in the frequency of HLA-DPB1 alleles was found in multiple sclerosis patients from Northern Ireland. Although present in the controls, linkage disequilibrium between HLA-DPB1*0101 and HLA-DR17 was not found in multiple sclerosis patients. PMID- 1420117 TI - A likelihood approach to HLA serology. AB - A likelihood approach to HLA serology has been developed in which the aim is not to define a recognition set for a serum but to describe the serum's ability to react with each and every antigen in the test cells, this ability being quantified in terms of the probability of a positive reaction. For a given set of probabilities, one for each antigen, it is possible to derive the probability of the observed set of reactions (the likelihood of the set of probabilities). The maximum possible value of the likelihood for any possible combination of the probability set can then be sought, but this requires a maximization of likelihood with respect to 60-100 independent parameters. Theoretical considerations of the shape of the likelihood surface prove that, in this particular case, this is a feasible proposition. This approach allows the recognition of three groups of antigens: those for which there is considerable evidence of a specificity, those for which there is either no specificity or a very weak specificity, and those for which there is insufficient evidence on which to base a conclusion. The existence of a specificity can be tested using a log likelihood ratio as a statistic, but the usual assumption of a chi 2 distribution of this statistic cannot automatically be made in this situation. Therefore, the distribution is estimated by simulation. A serologist using this approach would receive considerably more information as to the serum's reaction patterns and valid statistics for the existence, or not, of a specificity. PMID- 1420119 TI - Nomenclature for factors of the HLA system, 1991. PMID- 1420121 TI - [Publicity and truth in medicine]. PMID- 1420123 TI - The pathogenic classification of glaucomas. AB - On the basis of a pathogenic definition, our classification distinguished for each of the first intersections a main--mostly determinant mechanism and a secondary mechanism, mostly modulating the damages: hydrodynamic alteration and tissue resistance alteration--for the second intersection, outflow block and hypersecretion--for the third. Reflecting the state of present knowledge, from the corresponding forms of the disease, only outflow block glaucoma is completely analysed, the exogenous, trabecular, pretrabecular and mixed glaucomas being described. In order to permit the correct framing of all pretrabecular block glaucomas, the posterior push forms (retrovitreal or parietal) were introduced besides the anterior already described forms (pupillary or angular). As for low tissue resistance glaucomas, genetic, cardiovascular, metabolic, haematologic and ocular influences are mentioned. This classification avoids the theoretical inadvertencies of previous classifications offering the synthetic frame of a coherent system, open to any new developments, all inclusive, terminologically clear and with direct therapeutic references. PMID- 1420120 TI - Typing for class I HLA polymorphism: past, present, and future. PMID- 1420122 TI - [The role of accommodation in functional strabismus]. AB - The accommodative reflex unleash is produced by many stimuli, of which the most important are the lack of clarity of the retinal image and the convergence. The ciliary muscles, although innervated by vegetative fibres, behave like striated fibres. It is also discussed the role of accommodation in the appearance of functional strabismus. PMID- 1420124 TI - [The geographic environment--a risk factor in eyelid tumors?]. AB - The paper shows the role of the geographical environment in the incidence of various ophthalmological diseases and tries to make connections between different factors of pollution and the appearance of cancer, using epidemiological data. In Bihor district, the analysis of ocular tumors during a 25 years period shows 34 cases of malignant melanoma, 6 cases of glioma, 14 epibulbar malignant tumors opposing to 487 palpebral tumors, 3 tumors of the lacrimal sac and 8 cases of trichoepithelioma. Histopathologically, 173 of them were spinal cell epithelioma, 210 were basal cell epithelioma, 48 were sudoriferous, 40 were non-differentiated and 16 16 were mixed forms. The authors propose the district distributed study of the morbidity of various ocular diseases, which lead to the achievement of an ophthalmo-geography. PMID- 1420125 TI - [Pseudodominance in congenital glaucoma]. AB - By studying the genealogical tree of a 3.5-years-old child, on a three generations, we obtained values which have shown that the transmission in congenital glaucoma is sometimes of pseudo-dominant type. The obtained values are in accordance with the values in the medical literature. the percentage of the subjects affected by glaucoma being 66% and the maximum penetrance of the pathological gene. Our observations try to clear up the pseudo-dominant aspect in early congenital glaucoma. PMID- 1420126 TI - [Corneal rodent ulcer]. AB - It is presented the observation of a 67-years-old female patient with relapsed ulcus rodens at the right eye. Are also discussed the etiopathogenic mechanisms of the affection and the actual treatment principles, based on the mechanism of self immunity which stays at the basis of the disease's pathogeny. PMID- 1420127 TI - [Goldenhar's oculoauricular dysplasia, limbic dermoid and conjunctival dermolipoma]. AB - The paper presents two clinical observations on Goldenhar's syndrome which puts in associations multi-lesions of the first branchial arc. The first observation presents a dermoid of the limb, the second associates a conjunctival dermolipoma at one eye with dermoid of the limb at the other eye. Morphologically, these tumoral formations constitute dysgenetic heterotopias which present at the surface a weak keratinized epidermal, under which it may be identified a dense conjunctival tissue which contains pilosebaceous and sudoripous glands and also a well-represented adipose tissues at the dermolipoma level. PMID- 1420129 TI - Exuberant epibulbar tumor penetrating into the orbit in xeroderma pigmentosum. AB - The clinical and histopathological findings are described in a 10-year-old girl with xeroderma pigmentosum and multiple ophthalmic complications, including the eyelids, conjunctiva, orbit, cornea and iris; some of these complications took an unusual form. Histological examination following right orbital exenteration revealed an epibulbar squamous cell carcinoma penetrating the orbit and building a noose all around the ocular globe with subsequent strangulation. Moreover, a palpebral squamous cell carcinoma developed-independently from the right lower lid and, unconnected with the epibulbar tumor, penetrated to the orbit. PMID- 1420128 TI - [The elementary visual and psychovisual manifestations in cerebral circulatory insufficiency]. AB - A correlation between cerebral vascular topography and visual ways topography was made. The carotid vascularization intricates with the vertebral basilar vascularization, because the pre-geniculate and post-geniculate optical ways have mainly a carotid irrigation, while the diencephalic intermedial nervous centers and the final cortical nervous centers have mainly a vertebral basilar vascularization. It is shown that there are some individual arterial anatomical variations, two of which having a remarkable importance. The former refers to the carotid origin of the posterior cerebral arteria, which makes that the totality of visual ways being irrigated by carotid circulatory system. The latter refers to the Willis atypical polygons, which determine important atipies in the topographical distribution of the chiasma's arteries and optical bandelets. By visual field's modifications are sampled the different types of cerebral circulatory insufficiency. PMID- 1420130 TI - [Echography in ophthalmology]. AB - Echography represents an extremely valuable method in exploration of the eye for knowledge of some ocular parameters or detect and localize intraocular pathological process when the classical ophthalmological investigations are insufficient because of the affected transparent mediums. It is also used in the orbit pathology which is inaccessible to direct examination. This work contains the echographic exploration of the most common oculo-orbital diseases reached by ultrasonography (echography). The direct access of the ophthalmologist to the echograph enables the correlation between the anamnestic and clinical datum with those obtained by echographic explorations, meaning a more precise diagnosis. PMID- 1420131 TI - [Mesodermal dysgenesis of the anterior segment]. AB - A patient is 18 years old; he presents Peters' anomaly, microcornea, the persisting of papillar membrana, congenital specifying lens for both eyes and atypical iridic coloboma for the right eye. The eye sight is diminished under the limit of practice usefulness for both eyes. The disease is thought to be a mesodermal dysgenesis of the anterior segment having some persisting fetal structures. The absence of such lesions within the same family pleads for the action of a teratogen factor that have belated action during the 4th-5th month of pregnancy. PMID- 1420132 TI - [Sympathetic ophthalmia after a cataract operation]. AB - Sympathetic ophthalmia remains a dreadful complication of ocular traumas, accidentally but also surgically occurred; it may induced by certain ocular components, which are strongly antigenic, such as the uveal material or the recently discovered retinal material, represented by the interphotoreceptor binding protein and the S-antigen. The occurrence of the disease seems to be favoured by the transferring of the antigenic material through the conjunctival lymphatic mesh opened by the trauma. The paper presents a female patient with sympathetic ophthalmia occurred after cataract surgery. PMID- 1420134 TI - [Brachymorphy and cataract]. AB - A 43-years-old male patient presents pathological cataract at both eyes. The thorough somatic examination shows little size, with adiposity, short members with brachydactyly. It is discussed the presence of the pathological cataract as part of a mesodermal dysgenetic syndrome with brachymorphy and brachydactyly, different from the Weill-Marchesani syndrome. PMID- 1420135 TI - [Heredity in myopia]. PMID- 1420133 TI - [Congenital cataract associated with mental retardation and epilepsy]. AB - The paper presents the observations on a female patient with congenital cataract, oligophrenia, unsteady gait, low muscular strength, diminished osteotendinous reflexes. The patient has an under normally developed intellect, dysarthria, epileptic crises. Her speaking practice is bad, she also has tropical disturbances, genu valgum, shortening of the fingers of the right hand, kyphoscoliosis. The clinical signs integrate the observations with the Marinescu Sjogren syndrome. The case is interesting because of the association of the epilepsy with this syndrome. PMID- 1420136 TI - Aldose reductase: model for a new paradigm of enzymic perfection in detoxification catalysts. PMID- 1420137 TI - Site-directed mutations that alter the inhibitory activity of the tissue inhibitor of metalloproteinases-1: importance of the N-terminal region between cysteine 3 and cysteine 13. AB - The tissue inhibitor of metalloproteinases-1 (TIMP-1) was subjected to single site mutations within the N-terminal three loops using an oligonucleotide directed polymerase chain reaction method. All the histidines, and a number of other residues conserved between TIMP-1 and TIMP-2, were individually modified and the mutant TIMPs expressed in mammalian cells. Purified mutant TIMPs were shown to be correctly folded by measuring the effect of guanidine hydrochloride on intrinsic fluorescence. Kinetic analyses of mutants using a quenched fluorescent peptide substrate and the metalloproteinase PUMP indicated that mutation of His7 and Gln9 caused an increase in the apparent dissociation constant, largely due to an increase in the rate of dissociation of complexes. The data indicate that the anchored sequence between Cys 3 and Cys 13 is a key region for interaction of TIMP-1 with metalloproteinases. PMID- 1420138 TI - Proteolysis of an active site peptide of lactate dehydrogenase by human immunodeficiency virus type 1 protease. AB - The muscle and heart lactate dehydrogenase (LDHs) of rabbit and pig are specifically cleaved at a single position by HIV-1 protease, resulting in the conversion of 36-kDa subunits of the oligomeric enzymes into 21- and 15-kDa protein bands as analyzed by SDS-PAGE. While the proteolysis was observed at neutral pH, it became more pronounced at pH 6.0 and 5.0. The time courses of the cleavage of the 36-kDa subunits were commensurate with the time-dependent loss of both quaternary structure and enzymatic activity. These results demonstrated that deoligomerization of rabbit muscle LDH at acidic pH rendered its subunits more susceptible to proteolysis, suggesting that a partially denatured form of the enzyme was the actual substrate. Proteolytic cleavage of the rabbit muscle enzyme occurred at a decapeptide sequence, His-Gly-Trp-Ile-Leu*Gly-Glu-His-Gly-Asp (scissile bond denoted throughout by an asterisk), which constitutes a "strand loop" element in the muscle and heart LDH structures and contains the active site histidyl residue His-193. The kinetic parameters Km, Vmax/KmEt, and Vmax/Et for rabbit muscle LDH and the synthetic decapeptide Ac-His-Gly-Trp-Ile-Leu*Gly-Glu His-Gly-Asp-NH2 were nearly identical, suggesting that the decapeptide within the protein substrate is conformationally mobile, as would be expected for the peptide substrate in solution. Insertion of part of this decapeptide sequence into bacterial galactokinase likewise rendered this protein susceptible to proteolysis by HIV-1 protease, and site-directed mutagenesis of this peptide in galactokinase revealed that the Glu residue at the P2' was important to binding to HIV-1 protease. Crystallographic analysis of HIV-1 protease complexed with a tight-binding peptide analogue inhibitor derived from this decapeptide sequence revealed that the "strand-loop" structure of the protein substrate must adopt a beta-sheet structure upon binding to the protease. The Glu residue in the P2' position of the inhibitor likely forms hydrogen-bonding interactions with both the alpha-amide and gamma-carboxylic groups of Asp-30 in the substrate binding site. PMID- 1420139 TI - The three-dimensional structure of a glutathione S-transferase from the mu gene class. Structural analysis of the binary complex of isoenzyme 3-3 and glutathione at 2.2-A resolution. AB - The crystal structure of a mu class glutathione S-transferase (EC 2.5.1.18) from rat liver (isoenzyme 3-3) in complex with the physiological substrate glutathione (GSH) has been solved at 2.2-A resolution by multiple isomorphous replacement methods. The enzyme crystallized in the monoclinic space group C2 with unit cell dimensions of a = 87.98 A, b = 69.41 A, c = 81.34 A, and beta = 106.07 degrees. Oligonucleotide-directed site-specific mutagenesis played an important role in the solution of the structure in that the cysteine mutants C86S, C114S, and C173S were used to help locate the positions of mercuric ion sites in nonisomorphous derivatives with ethylmercuric phosphate and to align the sequence with the model derived from MIR phases. A complete model for the protein was not obtained until part of the solvent structure was interpreted. The dimer in the asymmetric unit refined to a crystallographic R = 0.171 for 19,298 data and I > or = 1.5 sigma (I). The final model consists of 4150 atoms, including all non-hydrogen atoms of 434 amino acid residues, two GSH molecules, and oxygen atoms of 474 water molecules. The dimeric enzyme is globular in shape with dimensions of 53 x 62 x 56 A. Crystal contacts are primarily responsible for conformational differences between the two subunits which are related by a noncrystallographic 2-fold axis. The structure of the type 3 subunit can be divided into two domains separated by a short linker, a smaller alpha/beta domain (domain I, residues 1-82), and a larger alpha domain (domain II, residues 90-217). Domain I contains four beta strands which form a central mixed beta-sheet and three alpha-helices which are arranged in a beta alpha beta alpha beta beta alpha motif. Domain II is composed of five alpha-helices. Domain I can be considered the glutathione binding domain, while domain II seems to be primarily responsible for xenobiotic substrate binding. The active site is located in a deep (19-A) cavity which is composed of three relatively mobile structural elements: the long loop (residues 33-42) of domain I, the alpha 4/alpha 5 helix-turn-helix segment, and the C-terminal tail. GSH is bound at the active site in an extended conformation at one end of the beta-sheet of domain I with its backbone facing the cavity and the sulfur pointing toward the subunit to which it is bound.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1420140 TI - Modular mutagenesis of exons 1, 2, and 8 of a glutathione S-transferase from the mu class. Mechanistic and structural consequences for chimeras of isoenzyme 3-3. AB - Exons 1 and 2 and exon 8 of the mu class GSH transferases from rat encode sequence-variable regions 1 and 4 of mu class isoenzymes, respectively. These two of four variable regions are located at the N- and C-termini of this isoenzyme class and impinge on the active site. In order to assess the influence of these variable regions on the catalytic diversity of the class mu isoenzymes, seven chimeric isoenzymes were constructed by transplantation of the variable regions of the sequence of the type 4 subunit into the corresponding regions of the type 3 subunit. The chimeric isoenzymes exhibit unique catalytic properties. Replacement of all, or part, of variable region 4 of the type 3 subunit with that of the type 4 subunit results in chimeric catalysts with higher turnover numbers in nucleophilic aromatic substitution reactions. Analysis of the crystal structure of isoenzyme 3-3 [Ji, X., Zhang, P., Armstrong, R. N., & Gilliland, G. L. (1992) Biochemistry (preceding paper in this issue)] suggests that interaction of the flexible C-terminal tail with the N-terminal domain helps limit the rate of product release from the active site of isoenzyme 3-3 in this type of reaction. Substitution of all, or part, of the sequence-variable region 1 of subunit 3 with that of subunit 4 results in chimeric isoenzymes that mimic the high stereoselectivity but not the catalytic efficiency of isoenzyme 4-4 toward alpha,beta-unsaturated ketones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420141 TI - Complete sequential 1H and 15N nuclear magnetic resonance assignments and solution secondary structure of the blue copper protein azurin from Pseudomonas aeruginosa. AB - Complete sequential 1H and 15N resonance assignments for the reduced Cu(I) form of the blue copper protein azurin (M(r) 14,000, 128 residues) from Pseudomonas aeruginosa have been obtained at pH 5.5 and 40 degrees C by using homo- and heteronuclear two-dimensional (2D) and three-dimensional (3D) nuclear magnetic resonance spectroscopic experiments. Combined analysis of a 3D homonuclear 1H Hartmann-Hahn nuclear Overhauser (3D 1H HOHAHA-NOESY) spectrum and a 3D heteronuclear 1H nuclear Overhauser 1H[15N] single-quantum coherence (3D 1H[15N] NOESY-HSQC) spectrum proved especially useful. The latter spectrum was recorded without irradiation of the water signal and provided for differential main chain amide (NH) exchange rates. NMR data were used to determine the secondary structure of azurin in solution. Comparison with the secondary structure of azurin obtained from X-ray analysis shows a virtually complete resemblance; the two beta-sheets and a 3(10)-alpha-3(10) helix are preserved at 40 degrees C, and most loops contain well-defined turns. Special findings are the unexpectedly slow exchange of the Asn-47 and Phe-114 NH's and the observation of His-46 and His-117 N epsilon 2H resonances. The implications of these observations for the assignment of azurin resonance Raman spectra, the rigidity of the blue copper site, and the electron transfer mechanism of azurin are discussed. PMID- 1420142 TI - NMR studies of the conformational change in human N-p21ras produced by replacement of bound GDP with the GTP analog GTP gamma S. AB - 1H-Detected 15N-edited NMR in solution was used to study the conformational differences between the GDP- and GTP gamma S-bound forms of human N-p21ras. The amide protons of 15N-labeled glycine and isoleucine were observed. Resonances were assigned to residues of particular interest, glycines-60 and -75 and isoleucines-21 and -36, by incorporating various 13C-labeled amino acids in addition to [15N]glycine and [15N]iosleucine and by replacing Mg2+ by Co2+. When GTP gamma S replaced GDP in the active site of p21ras, only 5 of the 14 glycine amide resonances show major shifts, indicating that the conformational effects are fairly localized. Responsive glycines-10, -12, -13, and -15 are in the active site. Gly-75, located at the far end of a conformationally-active loop and helix, also responds to substitution of GTP gamma S for GDP, while Gly-77 does not, supporting a role for Gly-75 as a swivel point for the conformational change. The amide proton resonances of isoleucines-36 and -21 and a third unidentified isoleucine also undergo major shifts upon replacement of GDP by GTP gamma S. Thus, the effector-binding loop containing Ile-36 is confirmed to be involved in the conformational change, and the alpha-helix containing Ile-21 is also shown to be affected. PMID- 1420143 TI - Compact denatured state of a staphylococcal nuclease mutant by guanidinium as determined by resonance energy transfer. AB - The protein from a mutant clone of staphylococcal nuclease with a cysteine substituting for a lysine at position 78 was prepared and labeled with a cysteine specific fluorescent probe 5-[[2-[(iodoacetyl)-amino]ethyl]amino]naphthalene-1 sulfonic acid (IAEDANS). Time-resolved nonradiative energy-transfer studies were done using the single tryptophan at position 140 as the energy donor and the IAEDANS as the receptor. Changes in distance and distance distributions were observed as a function of increasing guanidinium (GuHCl) concentration (0-2 M) and in the presence or absence of Ca2+ and inhibitor 2'-deoxythymidine 3',5' diphosphate (pdTp). In the native state, both the ternary complex and the noncomplexed protein are best fit with one population having an average donor acceptor distance of approximately 23 A and an "apparent" full width at half maximum (fwhm) of distance distribution of approximately 18 A. Besides the contribution of linker arm of the acceptor, it appears that there are some conformational heterogeneties either due to the disordering of the tryptophan region or due to the whole protein in the native state. During GuHCl unfolding, the average distance remains relatively constant up to GuHCl concentrations where both the ternary complex and the ligand-free protein are denatured (1-1.3 M). The compact denatured states persist up to 2 M GuHCl. At 2 M GuHCl, the heterogeneity of the denatured state in the ternary complex is much larger than that of the ligand-free nuclease. The results show that the denatured states of staphylococcal nuclease mutant K78C by GuHCl are compact and these compact denatured states are likely due to residual structures or incompletely disrupted hydrophobic cores under these conditions. PMID- 1420144 TI - Extracting information on folding from the amino acid sequence: accurate predictions for protein regions with preferred conformation in the absence of tertiary interactions. AB - A recently developed procedure to predict backbone structure from the amino acid sequence [Rooman, M., Kocher, J. P., & Wodak, S. (1991) J. Mol. Biol, 221, 961 979] is fine tuned to identify protein segments, of length 5-15 residues, that adopt well-defined conformations in the absence of tertiary interactions. These segments are obtained by requiring that their predicted lowest energy structures have a sizable energy gap relative to other computed conformations. Applying this procedure to 69 proteins of known structure, we find that regions with largest energy gaps--those having highly preferred conformations--are also the most accurately predicted ones. On the basis of previous findings that such regions correlate well with sites that become structured early during folding, our approach provides the means of identifying such sites in proteins without prior knowledge of the tertiary structure. Furthermore, when predictions are performed so as to ignore the influence of residues flanking each segment along the sequence, a situation akin to excising the considered peptide from the rest of the chain, they offer the possibility of identifying protein segments liable to adopt well-defined conformations on their own. The described approach should have useful applications in experimental and theoretical investigations of protein folding and stability, and aid in designing peptide drugs and vaccines. PMID- 1420145 TI - Relationships between secondary structure fractions for globular proteins. Neural network analyses of crystallographic data sets. AB - The relationship between the fractions of protein secondary structural components as determined from X-ray crystallographic data by the procedures of Kabsch and Sander (KS) and of Levitt and Greer (LG) is analyzed by neural network analysis of these two tabulations of literature data. A linear relationship between the KS and LG reductions of X-ray data to secondary structure descriptors is demonstrated by a regression analysis of the relationships between these sets of structural parameters. Back-propagation neural network analysis was then used to derive equations for determination of the most probable fractions of beta-sheet, bend, turn, and "other" conformations given the fraction of alpha-helix in a globular protein. The deviation of the X-ray values for beta-sheet from that determined with these equations was shown to have a variance that exponentially decreased with increasing fraction of alpha-helix. A second neural network analysis showed that knowledge of both the alpha-helical and beta-sheet fractions in a protein significantly reduces the uncertainty in prediction of the other components of the secondary structure. These analyses provide insight into the nature of the data sets derived from crystal structures. Since these complications of crystal structure data are commonly used as reference information for quantitative evaluation of spectra (for example, FTIR, Raman, and electronic or vibrational circular dichroism) in terms of secondary structure, such internal correlations in the reference sets may have significant effects on the stability of spectroscopic analyses derived from them. PMID- 1420148 TI - Covalent adducts between tRNA (m5U54)-methyltransferase and RNA substrates. AB - The interaction of tRNA (m5U54)-methyltransferase (RUMT) with in vitro synthesized unmodified tRNA and a 17-base oligoribonucleotide analog of the T-arm of tRNA in the absence of AdoMet has been investigated. Binary complexes are formed which are isolable on nitrocellulose filters and are composed of noncovalent and covalent complexes in nearly equal amounts. The covalent RUMT-RNA complexes are stable to SDS-PAGE and migrate slower than free enzyme or RNA. Kinetic and thermodynamic constants involved in formation and disruption of noncovalent and covalent binary complexes have been determined and interpreted in the context of steady-state kinetic parameters of the enzyme-catalyzed methylation and 5-H exchange of substrate. The results show that the isolable covalent complex is kinetically incompetent as an intermediate for methylation. Isotope trapping experiments show that when AdoMet is added to preformed binary complex, all bound tRNA is converted to methylated product; thus, the covalent complexes are chemically competent to form products. We have concluded that, after a reversible binary complex is formed, the catalytic thiol adds to the 6 carbon of the U54 of tRNA. The initial adduct leaves the reaction pathway to protonation at carbon 5; the latter can deprotonate and re-enter the pathway to form methylated product. It is speculated that covalent binary RUMT-RNA adducts may serve as depots of enzyme-tRNA complexes primed for methylation, or in unknown roles with RNAs other than tRNA. PMID- 1420146 TI - Vibrational circular dichroism studies of the A-to-B conformational transition in DNA. AB - The vibrational circular dichroism (VCD) spectra of several natural DNAs as well as tRNA, poly(dG-dC).poly(dG-dC), and poly(dA-dT).poly(dA-dT) are reported for the base deformation modes in the IR region from 1700 to 1550 cm-1 for the polymers in D2O as well as in high alcohol dehydrating conditions. Spectra of both the B- and A-forms were identified. The A-form DNA VCD, not previously reported, has characteristics that can be found in the VCD spectra of RNAs as would be expected from the similarity of their structures. The VCD is sequence dependent. Under the dehydrating conditions studied, poly(dA-dT)poly(dA dT),poly(dA).poly(dT), and a high-A-T fraction natural DNA had a different bandshape from the other DNAs, which was similar to that of poly(rA).poly(rU). Poly(dG-dC).poly-(dG-dC) did not form an A-form in high-alcohol conditions but instead had a VCD spectrum much like that of its high-salt-induced Z-form. Qualitative differences seen experimentally between A- and B-form DNA VCD were suggested by the differences in the coupled oscillator VCD calculated for the two forms. PMID- 1420147 TI - Mammalian DNA polymerase beta: characterization of a 16-kDa transdomain fragment containing the nucleic acid-binding activities of the native enzyme. AB - The 39-kDa DNA polymerase beta (beta-Pol) molecule can be readily converted into two constituent domains by mild proteolysis; these domains are represented in an 8-kDa N-terminal fragment and a 31-kDa C-terminal fragment [Kumar et al. (1990a) J. Biol. Chem. 265, 2124-2131]. Intact beta-Pol is a sequence-nonspecific nucleic acid-interactive protein that binds both double-stranded (ds) and single-stranded (ss) polynucleotides. These two activities appear to be contributed by separate portions of the enzyme, since the 31-kDa domain binds ds DNA but not ss DNA, and conversely, the 8-kDa domain binds ss DNA but not ds DNA [Casas-Finet et al. (1991) J. Biol. Chem. 266, 19618-19625]. Truncation of the 31-kDa domain at the N terminus with chymotrypsin, to produce a 27-kDa fragment (residues 140-334), eliminated all DNA-binding activity. This suggested that the ds DNA-binding capacity of the 31-kDa domain may be carried in the N-terminal segment of the 31 kDa domain. We used CNBr to prepare a 16-kDa fragment (residues 18-154) that spans the ss DNA-binding region of the 8-kDa domain along with the N-terminal portion of the 31-kDa domain. The purified 16-kDa fragment was found to have both ss and ds polynucleotide-binding capacity. Thermodynamic binding properties for these activities are similar to those of the intact enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420150 TI - Functional compensation of a recognition-defective transfer RNA by a distal base pair substitution. AB - A single G3:U70 base pair in the acceptor helix is the major determinant of alanine acceptance in alanine transfer RNAs. Transfer of this base pair into other transfer RNAs confers alanine acceptance. A G3:C70 substitution eliminates alanine acceptance in vivo and in vitro. In this work, a population of mutagenized G3:C70 alanine tRNA amber suppressors was subjected to a selection for mutations that compensate for the inactivating G3:C70 substitution. No compensatory mutations located in the acceptor helix were obtained. Instead, a U27:U43 substitution that replaced the wild-type C27:G43 in the anticodon stem created a U27:U43/G3:C70 mutant alanine tRNA that inserts alanine at amber codons in vivo. The U27:U43 substitution is at a location where previous footprinting work established an RNA-protein contact. Thus, this mutation may act by functionally coupling a distal part of the tRNA structure to the active site. PMID- 1420149 TI - Subunit complementation of thymidylate synthase. AB - Each of the two active sites of thymidylate synthase contains amino acid residues contributed by the other subunit. For example, Arg-178 of one monomer binds the phosphate group of the substrate dUMP in the active site of the other monomer [Hardy et al. (1987) Science 235, 448-455]. Inactive mutants of such residues should combine with subunits of other inactive mutants to form heterodimeric hybrids with one functional active site. In vivo and in vitro approaches were used to test this hypothesis. In vivo complementation was accomplished by cotransforming plasmid mixtures encoding pools of inactive Arg-178 mutants and pools of inactive Cys-198 mutants into a host strain deficient in thymidylate synthase. Individual inactive mutants of Arg-178 were also cotransformed with the C198A mutant. Subunit complementation was detected by selection or screening for transformants which grew in the absence of thymidine, and hence produced active enzyme. Many mutants at each position representing a wide variety of size and charge supported subunit complementation. In vitro complementation was accomplished by reversible dissociation and unfolding of mixtures of purified individual inactive Arg-178 and Cys-198 mutant proteins. With the R178F + C198A heterodimer, the Km values for dUMP and CH2H4folate were similar to those of the wild-type enzyme. By titrating C198A with R178F under unfolding-refolding conditions, we were able to calculate the kcat value for the active heterodimer. The catalytic efficiency of the single wild-type active site of the C198A + R178F heterodimer approaches that of the wild-type enzyme. PMID- 1420151 TI - Roles of Cys148 and Asp179 in catalysis by deoxycytidylate hydroxymethylase from bacteriophage T4 examined by site-directed mutagenesis. AB - The proposed roles of Cys148 and Asp179 in deoxycytidylate (dCMP) hydroxymethylase (CH) have been tested using site-directed mutagenesis. CH catalyzes the formation of 5-(hydroxymethyl)-dCMP, essential for DNA synthesis in phage T4, from dCMP and methylenetetrahydrofolate. CH resembles thymidylate synthase (TS), an enzyme of known three-dimensional structure, in both amino acid sequence and the reaction catalyzed. Conversion of Cys148 to Asp, Gly, or Ser decreases CH activity at least 10(5)-fold, consistent with a nucleophilic role for Cys148 (analogous to the catalytic Cys residue in TS). In crystalline TS, hydrogen bonds connect O4 and N3 of the substrate dUMP to the side-chain amide of an Asn; the corresponding residue in CH is Asp179. Conversion of Asp179 to Asn reduces the value of kcat/KM for dCMP by (1.5 x 10(4))-fold and increases the value of kcat/KM for dUMP by 60-fold; as a result, CH(D179N) has a slight preference for dUMP. Wild-type CH and CH(D179N) are covalently inactivated by 5 fluoro-dUMP, a mechanism-based inactivator of TS. Asp179 is proposed to stabilize covalent catalytic intermediates, by protonating N3 of the pyrimidine-CH adduct. PMID- 1420152 TI - Left-sided substrate binding of lysozyme: evidence for the involvement of asparagine-46 in the initial binding of substrate to chicken lysozyme. AB - The "right-sided" and "left-sided" substrate binding modes at the lower saccharide binding subsites (D-F sites) of chicken lysozyme were investigated by utilizing mutant lysozymes secreted from yeast. We constructed the following mutant lysozymes; "left-sided" substitution of Asn46 to Asp, deletion of Thr47, and insertion of Gly between Thr47 and Asp48 and "right-sided" substitution of Asn37 to Gly. Analyses of their activities and substrate binding abilities showed that Asn46 and Thr47 are involved in the initial enzyme-substrate complex and Asn37 is involved in the transition state. These results support an earlier proposal that interactions between substrate and residues at the left side of lysozyme stabilize a catalytically inactive enzyme-substrate complex, while interactions between substrate and residues at the right side stabilize the catalytically active complex [Pincus, M. R., & Scheraga, H. A. (1979) Macromolecules 12, 633-644]. These results are also consistent with the proposed kinetic mechanism for lysozyme reaction that the rearrangement of an initial enzyme-substrate complex (beta-complex) to another complex (gamma-complex) is required for catalytic hydrolysis [Banerjee S. K., Holler, E., Hess, G. P., & Rupley, J. A. (1975) J. Biol. Chem. 250, 4355-4367]. PMID- 1420153 TI - Insulin differentially regulates protein phosphotyrosine phosphatase activity in rat hepatoma cells. AB - We have studied the effect of insulin stimulation on phosphotyrosine phosphatase (PTPase) activity in the well-differentiated rat hepatoma cell line Fao. PTPase activity was measured using a 32P-labeled peptide corresponding to the major site of insulin receptor autophosphorylation. Of the PTPase activity in Fao cells, 14% was in the cytosolic fraction, whereas 86% was in the particulate fraction; this latter fraction also had a 4-fold higher specific activity. Purification of the particulate fraction by lectin chromatography resulted in a 50% increase in specific activity, although this glycoprotein-rich fraction contained only 1.5% of the total activity. Both the cytosolic and particulate PTPase fractions were active toward the tyrosyl-phosphorylated insulin receptor in vitro. The activity of the particulate fraction but not the cytosolic fraction was inhibited by addition of a micromolar concentration of a phosphorylated peptide corresponding to residues 1142-1153 of the human insulin receptor sequence. By contrast, addition of the nonphosphorylated peptide even at millimolar concentration was without effect. Both PTPase fractions were inhibited by Zn+ at similar concentrations, whereas the cytosolic PTPase activity was 10-fold more sensitive to vanadate inhibition. Treatment of cells with 100 nM insulin increased PTPase activity in the particulate fraction by 40% and decreased activity in the cytosolic fraction by 35%. These effects occurred within 15 min and were half maximal at 3-4 nM insulin. When assessed as total activity, the magnitude of the changes in PTPase activity in the particulate and cytosolic fractions could not be explained on the basis of a translocation of PTPases between the two pools.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420154 TI - Biochemical characterization and electron-transfer reactions of sym1, a Rhodobacter capsulatus reaction center symmetry mutant which affects the initial electron donor. AB - A 51 bp section of the Rhodobacter capsulatus photosynthetic reaction center M subunit gene (nucleotides M562-M612 of the pufM structural sequence) encoding amino acids M187-M203 was replaced by the homologous region of the L subunit gene. This resulted in the symmetrization of much of the amino acid environment of the reaction center initial electron donor, P. This is the first in a series of large-scale symmetry mutations and is referred to as sym1. The sym1 mutant was able to grow photosynthetically, indicating that reaction center function was largely intact. Isolated reaction centers showed an approximately 10-nm blue shift in the QY band of P. The standard free energy change between P* and P+BphA- determined from analysis of the long-lived fluorescence from quinone-reduced reaction centers decreased from about -120 meV in the wild-type to about -75 meV in the sym1 mutant. A 65-70% quantum yield of electron transfer from P* to P+QA- was observed, most of the yield loss occurring between P* and P+BphA-. The decay of the stimulated emission from P* was about 3-fold slower in this mutant than in the wild-type. Time-resolved spectral analysis of the charge-separated intermediates formed in sym1 reaction centers indicated that the major product was P+BphA-. A model-dependent analysis of the observed rates and electron transfer yields gave the following microscopic rate constants for sym1 reaction centers (wild-type values under the same conditions are given in parentheses): [formula: see text] Analysis of the sym1 mutant, mutants near P made by other groups, and interspecies variation of amino acids in the vicinity of P suggests that the protein asymmetry in the environment of the initial electron donor is important for optimizing the rate and yield of electron transfer, but is not strictly required for overall reaction center function. PMID- 1420155 TI - The low-spin heme site of cytochrome o from Escherichia coli is promiscuous with respect to heme type. AB - Cytochrome o of Escherichia coli is able to incorporate two different structures of heme, either heme B (protoheme) or heme O, in its low-spin heme site. In contrast, the heme of the binuclear O2 reduction site is invariably heme O. Heme O is a newly discovered heme that is related to heme A, but with the formyl group of the latter replaced by methyl. Enzyme isolated from wild type E. coli has predominantly heme B in the low-spin site, whereas enzyme isolated from various overexpressing strains contains both types of enzyme in different proportions. In some strains, 70% of the enzyme has heme O in the low-spin site. Despite this variation in the structure of one of the prosthetic groups, the enzymatic activity and polypeptide composition of the enzyme remain virtually constant. EPR and activity data both indicate that heme B and heme O occupy the same low-spin heme site in the enzyme. With heme O in this site, the alpha-absorption band is narrower and further to the blue, and the Em,7 is lower, than when there is heme B in the site. In contrast to previous proposals, we show here that the enzyme does not exhibit significant spectral interactions between the hemes. The structural heterogeneity of the low-spin heme accounts for the variation in the optical spectra and redox properties of the enzyme as isolated from different strains of E. coli. PMID- 1420158 TI - Interaction of annexin VI with membranes: highly restricted dissipation of clustered phospholipids in membranes containing phosphatidylethanolamine. AB - Association of annexin VI with membranes induced extensive clustering of acidic phospholipids as detected by self-quenching of fluorescent-labeled acidic phospholipids [Bazzi, M.D., & Nelsestuen, G.L. (1991) Biochemistry 30, 7961]. The present study examined the rates of protein-induced clustering of acidic phospholipids in membranes containing 10-15% fluorescent-labeled phosphatidic acid dispersed in phosphatidylcholine (PC) or phosphatidylethanolamine (PE). Both membranes supported similar levels of protein-induced fluorescence quenching. With membranes containing PC, protein-membrane association and fluorescence quenching were rapid, and were virtually complete within seconds after the reagents were mixed. Membranes containing PE exhibited rapid protein-membrane association, but showed a fluorescence quenching that was several orders of magnitude slower than membranes containing PC. Calcium chelation resulted in rapid dissociation of protein-membrane complexes. Subsequent recovery of the fluorescence signal of both membranes was virtually complete, but the rate of fluorescence recovery was very different. The recovery was rapid in membranes containing PC, while PE-containing membranes showed slow recovery that approached the rate at which the fluorescent-labeled phosphatidic acid exchanged between vesicles. Thus, the presence of PE appeared to severely restrict dissipation of clustered phospholipids in membranes. Membranes containing PE, N-methyl-PE, N,N dimethyl-PE, and PC showed successive increases in the rates of fluorescence quenching and recovery, suggesting that hydrogen bonding between head groups was the basis for this property. If the restricted dissipation of phosphatidic acid in PE membranes is a general property, the relative mobility of membrane components and even diffusion on interior cell membranes may be greatly influenced by this phenomenon. PMID- 1420156 TI - Determination of recognition nucleotides for Escherichia coli phenylalanyl-tRNA synthetase. AB - The nucleotides in Escherichia coli tRNA(Phe) required for recognition by its cognate synthetase have been determined in vitro by measuring the kinetic parameters for aminoacylation using mutant tRNA(Phe) transcripts with purified E. coli tRNA(Phe) synthetase. The substitution of 11 nucleotides in E. coli tRNA(Phe) is shown to decrease the kcat/KM by as much as 1000-fold relative to the wild type. The most important recognition elements are the three anticodon nucleotides G34, A35, and A36. The recognition set also includes nucleotides in the variable pocket (U20 and U59), the acceptor end (A73), and the tRNA central core (G10, C25, A26, G44, and U45). Many of the recognition nucleotides are also among the residues comprising the identity set determined in vivo using an amber suppressor tRNA(Phe) [McClain, W. H., & Foss, K. (1988) J. Mol. Biol. 202, 697 709]. As could be anticipated from the very different methods used, some nucleotides in the identity set determined by the suppressor method were not among the recognition nucleotides and vice versa. The E. coli tRNA(Phe) recognition data can also be compared to the recognition sets for yeast and human tRNA(Phe) determined previously. The results indicate that the mechanism by which phenylalanyl-tRNA synthetases recognize their substrates seems to have diverged somewhat among different species. For example, nucleotide 20 in the D-loop, the anticodon nucleotides and the discriminator base 73 are important for the recognition by all three enzymes. However, recognition of the tRNA central core nucleotides is unique to E. coli FRS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420157 TI - Structure determination of the cyclohexene ring of retinal in bacteriorhodopsin by solid-state deuterium NMR. AB - The orientation and conformation of retinal within bacteriorhodopsin of the purple membrane of Halobacterium halobium was established by solid-state deuterium NMR spectroscopy, through the determination of individual chemical bond vectors. The chromophore ([2,4,4,16,16,17,17,17,18,18-2H11]retinal) was specifically deuterium-labeled on the cyclohexene ring and incorporated into the protein. A uniaxially oriented sample of purple membrane patches was prepared and measured at a series of inclinations relative to the spectrometer field. 31P NMR was used to characterize the mosaic spread of the oriented sample, and computer simulations were applied in the analysis of the 2H NMR and 31P NMR spectral line shapes. From the deuterium quadrupole splittings, the specific orientations of the three labeled methyl groups on the cyclohexene ring could be calculated. The two adjacent methyl groups (on C1) of the retinal were found to lie approximately horizontal in the membrane and make respective angles of 94 degrees +/- 2 degrees and 75 degrees +/- 2 degrees with the membrane normal. The third group (on C5) points toward the cytoplasmic side with an angle of 46 degrees +/- 3 degrees. These intramolecular constraints indicate that the cyclohexene ring lies approximately perpendicular to the membrane surface and that it has a (6S)-trans conformation. From the estimated angle of the tilt of the chomophore long axis, it is concluded that the polyene chain is slightly curved downward to the extracellular side of the membrane. PMID- 1420159 TI - Mammalian facilitative glucose transporters: evidence for similar substrate recognition sites in functionally monomeric proteins. AB - Four facilitative glucose transporters isoforms, GLUT1/erythrocyte, GLUT2/liver, GLUT3/brain, and GLUT4/muscle-fat, as well as chimeric transporter proteins were expressed in Xenopus oocytes, and their properties were studied. The relative Km's of the transporters for 2-deoxyglucose were GLUT3 (Km = 1.8 mM) > GLUT4 (Km = 4.6 mM) > GLUT1 (Km = 6.9 mM) > GLUT2 (Km = 17.1 mM). In a similar fashion, the uptake of 2-deoxyglucose by GLUT1-, GLUT2-, and GLUT3-expressing oocytes was inhibited by a series of unlabeled hexoses and pentoses and by cytochalasin B in a similar hierarchical order. To determine if the functional unit of the glucose transporter was a monomer or higher-order multimer, the high-affinity transporter GLUT3 was coexpressed with either the low-affinity GLUT2 or a GLUT3 mutant which contained a transport inactivating Trp410-->Leu substitution. In oocytes expressing both GLUT2 and GLUT3, the transport activity associated with each transporter isoform could be distinguished kinetically. Similarly, there was no alteration in the kinetic parameters of GLUT3, or the ability of glucose or cytochalasin B to inhibit 2-deoxyglucose uptake, when coexpressed with up to a 3 fold greater amount of functionally inactive mutant of GLUT3. These studies suggest that the family of glucose transporters have similar binding sites which may be in the form of a functional monomeric unit when expressed in Xenopus oocytes. PMID- 1420160 TI - Calmodulin-specific monoclonal antibodies inhibit DNA replication in mammalian cells. AB - The involvement of calmodulin in the proliferation of Chinese hamster embryo fibroblast cells has been studied with a specific monoclonal antibody to calmodulin. We observed that calmodulin levels increase 2-fold in the late G1 period in these cells, and this coincides with the increase in DNA polymerase alpha activity as the cells progress synchronously from a quiescent state in the G1 to the S phase. However, there is a concurrent 10-fold enhancement of thymidine kinase activity, which is tightly coupled to the entry of cells into the S phase. Incubation of permeabilized S-phase cells with calmodulin-specific murine monoclonal antibody resulted in a dose-dependent inhibition of DNA replication. This inhibitory effect of anti-calmodulin antibodies on DNA replication is completely reversed by the addition of exogenously purified calmodulin. These observations provide evidence for the involvement of calmodulin in DNA replication and, therefore, in cell proliferation during the S phase. PMID- 1420161 TI - Loop mobility in a four-helix-bundle protein: 15N NMR relaxation measurements on human interleukin-4. AB - 15N NOE, T1, and T2 measurements have been carried out on uniformly 15N-labeled human interleukin-4. Analysis of the results in terms of order parameters (S2) shows that although the helical core of this four-helix-bundle protein exists as a well-defined structure with limited conformational flexibility (S2 congruent to 0.9), other regions of the molecule experience substantial fluctuations in the conformation of the main chain (S2 = 0.3-0.8). These regions include both the N- and C-termini and two of the loops joining the helices. The majority of these internal motions are fast compared with the overall rotational correlation time (tau R = 7.6 ns at 35 degrees C) and are localized in regions that are relatively ill-defined in the NMR structures previously determined for this protein [Smith, L. J., Redfield, C., Boyd, J., Lawrence, G. M. P., Edwards, R. G., Smith, R. A. G., & Dobson, C. M. (1992) J. Mol. Biol. 224, 899-904]. Other motions are on a slower time scale and appear to be associated with two of the three disulfide bonds and the beta-sheet region in the protein. The dynamic properties of interleukin-4 in solution have been compared with features of the X-ray structures of other four-helix-bundle proteins. The results suggest that the dynamic properties observed here may be general for this class of proteins and may be significant for the interpretation of both their structural and functional properties. PMID- 1420162 TI - Spectroscopic studies of arsenic(III) binding to Escherichia coli RI methyltransferase and to two mutants, C223S and W183F. AB - The interactions of an arsenic (III) reagent, (CH3)2AsSCH2CONH2, with two Escherichia coli RI methyltransferase mutants, W183F and C223S, have been studied by phosphorescence, optically detected magnetic resonance, and fluorescence spectroscopy. The phosphorescence spectrum of the W183F mutant containing only one tryptophan at position 225 reveals a single 0,0-band that is red-shifted by 9.8 nm upon binding of As(III). Fluorescence titration of W183F with (CH3)2AsSCH2CONH2 produces a large tryptophan fluorescence quenching. Analysis of the quenching data points to a single high-affinity As(III) binding site that is associated with the fluorescence quenching. Triplet-state kinetic measurements performed on the perturbed tryptophan show large reductions in the lifetimes of the triplet sublevels, especially that of the T chi sublevel. As(III) binding to the enzyme at a site very close to the Trp225 residue induces an external heavy atom effect, showing that the perturber atom is in van der Waals contact with the indole chromophore. In the case of the C223S mutant, a single tryptophan 0,0-band also is observed in the phosphorescence spectrum, but no change occurs upon addition of the As(III) reagent. Fluorescence titration of C223S with As(III) shows essentially no quenching of tryptophan fluorescence, in contrast with W183F. These results, along with previous triplet-state and biochemical studies on the wild-type enzyme [Tsao, D. H.H., & Maki, A. H. (1991) Biochemistry 30, 4565-4572], show that As(III) binds with high affinity to the Cys223 residue and that the Trp225 side chain is located close enough to that of Cys223 to produce a heavy-atom perturbation when As(III) is bound. PMID- 1420163 TI - Resonance Raman studies of the protocatechuate 3,4-dioxygenase from Brevibacterium fuscum. AB - Resonance Raman studies of the protocatechuate 3,4-dioxygenase (PCD) from Brevibacterium fuscum have been carried out to take advantage of the high iron site homogeneity of this enzyme. Native uncomplexed PCD exhibits individual resonance-enhanced nu CO and delta CH vibrations for the two tyrosinates coordinated to the active site iron center, which can be assigned to a particular residue by their excitation profiles. Of the two nu CO features observed at 1254 and 1266 cm-1, only the latter is upshifted (to 1272 cm-1) when H2O is replaced by D2O. Similarly the 1254-cm-1 feature is unaffected, while the 1266-cm-1 feature is shifted to approximately 1290 cm-1 when inhibitors such as phenolates or terephthalate bind to the active site. These observed shifts can be rationalized by the presence of hydrogen-bonding interactions with solvent in the active site cavity, which are modulated by D2O and eliminated upon inhibitor binding. Examination of the PCD crystal structure suggests that the axial tyrosine can be hydrogen bonded in the uncomplexed enzyme to water molecules present in the substrate binding pocket. The equatorial tyrosine may also be hydrogen bonded but to solvent molecules which are trapped in a pocket inaccessible to bulk solvent. These studies allow for the first time the association of particular Raman spectroscopic features, i.e., the nu CO's at 1254 and 1266 cm-1, with the equatorial and axial tyrosine residues in the PCD active site, respectively; they lay the groundwork for further Raman studies on catalytically important species to determine the roles these tyrosine residues may play in the PCD reaction cycle. PMID- 1420164 TI - 1.67-A X-ray structure of the B2 immunoglobulin-binding domain of streptococcal protein G and comparison to the NMR structure of the B1 domain. AB - The structure of the B2 immunoglobulin-binding domain of streptococcal protein G has been determined at 1.67-A resolution using a combination of single isomorphous replacement (SIR) phasing and manual fitting of the coordinates of the NMR structure of B1 domain of streptococcal protein G [Gronenborn, A. M., et al. (1991) Science 253, 657-661]. The final R value was 0.191 for data between 8.0 and 1.67 A. The structure described here has 13 residues preceding the 57 residue Ig-binding domain and 13 additional residues following it, for a total of 83 residues. The 57-residue binding domain is well-determined in the structure, having an average B factor of 18.0. Only residues 8-77 could be located in the electron density maps, with the ends of the structure fading into disorder. Like the B1 domain, the B2 domain consists of four beta-strands and a single helix lying diagonally across the beta-sheet, with a -1, +3 chi, -1 topology. This small structure is extensively hydrogen-bonded and has a relatively large hydrophobic core. These structural observations may account for the exceptional stability of protein G. A comparison of the B2 domain X-ray structure and the B1 domain NMR structure showed minor differences in the turn between strands and two and a slight displacement of the helix relative to the sheet. Hydrogen bonds between crystallographically related molecules account for most of these differences. PMID- 1420166 TI - Effects of the steroid antagonist RU486 on dimerization of the human progesterone receptor. AB - We previously reported, using a coimmunoprecipitation assay, that the B form (PR B) of the human progesterone receptor from T47D human breast cancer cells dimerizes in solution with the A receptor (PR-A) and that the extent of dimerization correlates with receptor binding activity for specific DNA sequences [DeMarzo, A.M., Beck, C.A., Onate, S.A., & Edwards, D.P. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 72-76]. This suggested that solution dimerization is an intermediate step in the receptor activation process. The present study has tested the effects of the progesterone antagonist RU486 on solution dimerization of progesterone receptors (PR). As determined by the coimmunoprecipitation assay, RU486 binding did not impair dimerization of receptors; rather, the antagonist promoted more efficient solution dimerization than the progestin agonist R5020. This enhanced receptor dimerization correlated with a higher DNA binding activity for transformed receptors bound with RU486. RU486 has been shown previously to produce two other alterations in the human PR when compared with R5020. PR-RU486 complexes in solution exhibit a faster sedimentation rate (6 S) on salt containing sucrose density gradients than PR-R5020 complexes (4 S), and PR-DNA complexes have a faster electrophoretic mobility on gel-shift assays in the presence of RU486. We presently show that the 6 S PR-RU486 complex is a receptor monomer, not a dimer. The increased sedimentation rate and increased mobility on gel-shift assays promoted by RU486 were also observed with recombinant PR-A and PR-B separately expressed in insect cells from baculovirus vectors. These results suggest that RU486 induces a distinct conformational change both in PR monomers in solution and in dimers bound to DNA. We also examined whether conformational changes in PR induced by RU486 would prevent a PR polypeptide bound to RU486 from heterodimerization with another PR polypeptide bound to R5020. To evaluate this, PR-A and PR-B that were separately bound to R5020 or RU486 in whole cells were mixed in vitro. PR-A-RU486 was capable of dimerization with PR-B-R5020, and this was demonstrated for heterodimers both formed in solution and bound to specific DNA. The capability to form heterodimers in vitro raises the possibility that the antagonist action of RU486 in vivo could in part be imposed in a dominant negative fashion through heterodimerization between one receptor subunit bound to an agonist and another bound to RU486. PMID- 1420165 TI - Molecular cloning of porcine alveolar macrophage-derived neutrophil chemotactic factors I and II; identification of porcine IL-8 and another intercrine-alpha protein. AB - Alveolar macrophages (AM) mediate lung inflammation by producing lipid and peptide molecules that attract neutrophils (PMN) to the lung. Recently we described two porcine proteins called alveolar macrophage-derived chemotactic factors, AMCF-I and -II, that are potent, efficacious, and specific PMN chemoattractants both in vitro and in vivo. We report here the cloning of the full-length cDNAs which code for each protein. Porcine AM were stimulated for 4 h in vitro with Escherichia coli endotoxin (LPS), and a cDNA library was created from poly(A)(+)-selected mRNA. Specific oligonucleotide probes for AMCF-I and AMCF-II were amplified from the porcine AM cDNA library by the polymerase chain reaction using degenerate oligonucleotide primer pairs derived from the N terminal amino acid sequences of the proteins. These probes were used to isolate 2 full-length cDNAs of 1466 (AMCF-I) and 1515 (AMCF-II) base pairs. Both cDNAs code for proteins with four cysteine residues containing the C-X-C sequence characteristic of the intercrine-alpha family of neutrophil chemoattractants. AMCF-I shares 74% identity with human IL-8 and 84% identity with rabbit IL-8, and likely represents the porcine homologue of IL-8. By contrast, AMCF-II has no obvious human homologue. AMCF-II shares 53% identity with human neutrophil activating peptide 2. Its shared identity with the GRO-related proteins is as high as 61% (rat CINC/GRO), and its shared identity with the 78 amino acid epithelial cell-derived neutrophil activator (ENA-78) is 67%. AMCF-II may represent a new member of the intercrine-alpha family of neutrophil chemoattractants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420168 TI - Unusual DNA conformation at low pH revealed by NMR: parallel-stranded DNA duplex with homo base pairs. AB - We have investigated the conformational potentials of several DNA oligonucleotides containing sequences related to 5'-CGA in neutral pH and low pH (< 5.0) conditions. One-dimensional proton NMR spectra show that d(CGATCG), d(TCGATCGA), and d(CGATCGATCG) exhibit new sets of resonances at low pH (approximately 3.8-4.4), when compared to those from the neutral pH samples. The low pH form and the neutral pH form are in slow equilibrium. Analyses of the data suggest that these sequences under low pH conditions adopt structures distinct from B-DNA. Two-dimensional nuclear Overhauser effect spectroscopy (2D NOESY) data from the DNA hexamer d(CGATCG) of the neutral and low pH samples were used to analyze their respective structures in solution. An iterative NOE spectral driven refinement procedure, SPEDREF [Robinson, H., & Wang, A. H.-J. (1992) Biochemistry 31, 3524-3533], was used to show that the neutral pH structure is close to canonical B-DNA. In contrast, analysis of the low pH form using the 2D NOESY data suggests that its structure is consistent with a right-handed parallel stranded (PS) double helix with symmetrical non-Watson-Crick (C+:C, G:G, A:A, T:T) homo base pairs. Supporting evidence for the PS helix includes the asymmetric inversion-recovery relaxation times associated with the two ends of the helix. The structure is favored by the 5'-CGA sequence in which the cytosines provide the C+:C pairing for the nucleation step and the GpA step is significantly stabilized by the interstrand G-A stacking interactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420167 TI - Passage of RNA polymerase from open complex to elongation mode at the Escherichia coli lacUV5 promoter: nucleolytic hypersensitivity as a probe for complex conformational changes. AB - In transcriptionally active complexes between RNA polymerase and promoters, the center of the melted region is hyperreactive to the nucleolytic activity of the cuprous complex of 1,10-phenanthroline (OP-Cu). In the first part of this work, using synthetic oligonucleotides and exploiting gel retardation assays, I demonstrate that DNA unpairing is not the only determinant of this hyperreactivity. Polymerase binding is directly implicated, presumably participating in the stabilization of an intermediate required for the cutting. In the second part of the work, I show that, from fine analysis of the nucleolytic pattern of lacUV5 promoter DNA towards OP-Cu and Phe OP-Cu, it is possible to locate polymerase and to characterize its contacts at any time during the early stages of transcription. This analysis provides a description of the passage from the "open complex" to the elongation mode in terms of, first, release of the upstream contacts, and second, loss of sigma subunit. Occupancy of the overlapping promoter, P2, has a positive effect on the escape of polymerase from abortive cycling. The involvement of sigma and beta subunits in the reactivity pattern is discussed with respect to previous cross-linking studies. PMID- 1420169 TI - Enzymatic properties of the RecA803 protein, a partial suppressor of recF mutations. AB - The RecA803 protein suppresses the recombinational repair defect of recF mutations and displays enhanced joint molecule formation in vitro (Madiraju et al., 1988). To understand the physical basis for these phenomena, the biochemical properties of RecA803 protein were compared with those of the wild-type protein. The RecA803 protein shows greater DNA-dependent ATPase activity than the wild type protein with either M13 single-stranded (ss) DNA, which contains secondary structure, or double-stranded DNA. This increased activity reflects an enhanced ability of the mutant protein to form active complexes with these DNA molecules rather than an enhanced catalytic turnover activity, because identical kcat values for ATP hydrolysis are obtained when DNA substrates lacking secondary structure are examined. In addition, the ssDNA-dependent ATPase activity of RecA803 protein displays greater resistance to inhibition by SSB (single-stranded DNA binding) protein. These properties of the RecA803 protein are not due to either an increased binding affinity for ssDNA or an increased kinetic lifetime of RecA803 protein-ssDNA complexes, demonstrating that altered protein-DNA stability is not the basis for the enhanced properties of RecA803 protein. However, the nucleation-limited rate of association with ssDNA is more rapid for the RecA803 protein than for wild-type RecA protein. Consequently, we suggest that altered protein-protein interactions may account for the differences between these two proteins. The implications of these results with regard to the partial suppression of recF mutations by recA803 are discussed (Madiraju et al., 1988). PMID- 1420170 TI - Labeling of two different regions of the nucleotide binding site of the uncoupling protein from brown adipose tissue mitochondria with two ATP analogs. AB - The nucleotide binding site of the uncoupling protein (UCP) from brown adipose tissue was mapped by photoaffinity labeling with 2-azidoadenosine 5'-triphosphate (2-azido-ATP) and by affinity labeling with 3'-O-(5-fluoro-2,4 dinitrophenyl)adenosine 5'-triphosphate (FDNP-ATP). Both analogs bind with high affinity and specificity to the UCP in intact mitochondria, as well as to the isolated solubilized protein. Reversible binding at 4 degrees C in the dark is competitively blocked by GTP. Like the natural ligands ATP and GTP, both analogs are capable of inhibiting the H+/OH- conductance of the UCP as measured in proteoliposomes with reconstituted UCP. 2-azido-ATP was incorporated into UCP in mitochondria in the presence of carboxyatractylate, while FDNP-ATP was inserted into isolated UCP by prolonged incubation at room temperature under pH variation. Both reactions can be blocked by GTP. The incorporation of 2-azido-ATP could be localized between residues 258 and 283 by cleavage with CNBr. Solid-phase sequencing of the homoserine-linked radioactive peptide indicated that the 2 azido-ATP was linked to threonine-263. The incorporation of FDNP-ATP could be assigned by cleavage with CNBr and alternatively with trypsin at a locus of covalent attachment between residues 238 and 255. On the basis of published data that no tyrosine participates in nucleotide binding of the UCP, the probable residue reacting with FDNP-ATP is cysteine-253.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420171 TI - Modification of cytochrome P450 1A2 enzymes by the mechanism-based inactivator 2 ethynylnaphthalene and the photoaffinity label 4-azidobiphenyl. AB - 2-Ethynylnaphthalene (2EN) had previously been demonstrated to be a mechanism based inactivator of rat cytochrome P450 (P450) 1A2 [Hammons, G.J., Alworth, W.L., Hopkins, N.E., Guengerich, F. P., & Kadlubar, F. F. (1989) Chem. Res. Toxicol. 2, 367-374]. In this work 2EN was also demonstrated to be a useful inactivator of rabbit P450 1A2 (k(inactivation) 0.094 min-1, K(i) 11 microM) but it did not inactivate human P450 1A2, although the sequences of the three proteins are approximately 80% identical. Rat and rabbit P450 1A2 were modified by incubation with NADPH-P450 reductase, NADPH, and [3H]2EN to levels of 0.35 and 0.47 nmol of adduct (nmol of P450)-1, respectively. In each case only a single tryptic peptide was labeled; recovery of labeled peptides was low under the acidic HPLC conditions. The rabbit P450 1A2 peptide FQELMAAVGR (positions 175 184) and the rat P450 1A2 peptide L(S)QQYGDVLQIR (positions 67-78) were identified. 4-Azidobiphenyl (4-N3BP) was developed as a photoaffinity label for P 450 1A2 proteins because of its similarity to 4-aminobiphenyl, a known substrate for the enzymes. 4-N3BP was shown to be photolyzed with 350-nm light and radioactive label could be incorporated into rat P450 1A2. Labeling of the protein was found to be saturable with increasing concentrations of 4-N3BP and up to 0.59 nmol of label could be incorporated (nmol P450 1A2)-1. The substrate 4 aminobiphenyl and the competitive inhibitor 7,8-benzoflavone blocked photolabeling of P450 1A2 with 4-N3BP, and 4-N3BP inhibited N-hydroxylation of 4 aminobiphenyl by P450 1A2 in the usual enzyme assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420174 TI - Molecular thermodynamic model to predict the alpha-helical secondary structure of polypeptide chains in solution. AB - The native state of a protein molecule in aqueous solutions represents one of the lowest states of Gibbs energy [Anfinsen, C.B. (1973) Science 181, 223-230]. Much progress has been made about the rules of protein folding [King, J. (1989) Chem. Eng. News 67, 32-54] and the dominant forces in protein folding [Dill, K.A. (1990) Biochemistry 29, 7133-7155]. However, the quantitative contributions of different Gibbs energy terms to protein stability remains a controversial issue [Moult, J., & Unger, R. (1991) Biochemistry 30, 3816-3824]. A molecular thermodynamic model has been proposed for the Gibbs energy of folding a residue in aqueous homopolypeptides from a random-coiled state to either the alpha-helix state or the beta-sheet state [Chen, C.-C., Zhu, Y., King, J.A., & Evans, L.B. (1992) Biopolymers 32, 1375-1392]. In this work, we present a generalization of the molecular thermodynamic model for the Gibbs energy of folding natural and synthetic heteropolypeptides from random-coiled conformations into alpha-helical conformations. The generalized model incorporates the intrinsic folding potential due to residue-solvent interactions, the cooperative folding effect due to residue-residue interactions, and the location and length of alpha-helices. The utility of the model was demonstrated by examining the stability of alpha-helical conformations of a number of natural polypeptides including C-peptide (residues 1 13) and S-peptide (residues 1-20) of RNase A (bovine pancreatic ribonuclease A), the P alpha fragment in BPTI (bovine pancreatic trypsin inhibitor), and synthetic polypeptides (the copolymers of different amino acid residues) including alanine based peptides (16 or 17 residues long) in water. The computed Gibbs energies correspond well with the experimental data on helicity. The results also accounted for the effects of amino acid substitution and temperature on the stability of alpha-helical conformations of the test polypeptides. PMID- 1420172 TI - Phospholipase A2 engineering. The structural and functional roles of aromaticity and hydrophobicity in the conserved phenylalanine-22 and phenylalanine-106 aromatic sandwich. AB - The highly conserved phenylalanine-22 and phenylalanine-106, arranged as an aromatic sandwich, form part of an invariant hydrophobic wall that shields the active site of bovine pancreatic phospholipase A2 (PLA2) from bulk solvent [Dijkstra, B. W., Drenth, J., & Kalk, K. H. (1981) Nature 289, 604-606]. The residues have also been suggested to interact with the sn-2 acyl chain of bound phospholipid substrate [White, S. P., Scott, D. L., Otwinowski, Z., Gelb, M. H., & Sigler, P. B. (1990) Science 250, 1560-1563]. We now report the importance of these two residues in the structure and function of PLA2 in terms of aromaticity (changing to Ile) and hydrophobic (changing to Ala) and hydrophilic (changing to Tyr) character of these residues. The structural properties of the mutants were analyzed by proton NMR and by guanidine hydrochloride-induced denaturation. The functional properties were determined by measuring kinetic parameters toward various substrates in the forms of monomers, micelles, and vesicles, and by measuring equilibrium dissociation constants at the interface. The results show that (i) The conformational stability of each mutant was as good as that of wild type PLA2; none of the mutants was significantly perturbed structurally as judged from detailed 1H NMR analysis. These results suggest that neither the Phe-22/Phe 106 face-to-face pair nor the Phe-22/Tyr-111 edge-to-face pair plays a significant structural role. (ii) Mutations to Ile at either position 22 or position 106 resulted in only minor perturbations in activity. This suggests that the aromaticity is not important to the function of these two residues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420173 TI - Role of disulfide exchange in alpha 1-protease inhibitor. AB - The major endogenous inhibitor of neutrophil elastase in the plasma, alpha 1 protease inhibitor (alpha 1-PI), has a single cysteine residue which has been shown to form mixed disulfides with a number of thiols in vitro. Under normal physiological conditions, the plasma concentrations of reduced and oxidized thiols are such that a major fraction of alpha 1-PI in the circulation in vivo is in the form of mixed disulfides [Laurell, C.-B. (1979) in The Chemistry and Physiology of Human Plasma Proteins (Bing, D. H., Ed.) pp 329-341, Pergamon, New York]. We show here that the mixed disulfide between glutathione or cysteine and alpha 1-PI (alpha 1-PI-SSG or alpha 1-PI-SScys) has an intrinsic fluorescence which distinguishes it from the reduced form of alpha 1-PI. By employing the fluorescence difference, we have measured the ratio of alpha 1-PI-SH to mixed disulfide alpha 1-PI in redox buffers of different ratios of reduced to oxidized glutathione (GSH to GSSG) or reduced to oxidized cysteine (cys to cysSScys) and have calculated an equilibrium constant and redox potential of 0.74 +/- 0.08 and 8 +/- 2 mV, respectively, for the alpha 1-PI-SH/alpha 1-PI-SSG couple and of 0.32 +/- 0.02 and 29 +/- 2 mV, respectively, for the alpha 1-PI-SH/alpha 1-PI-SScys couple. We are unable to detect any change in Trp fluorescence in the complex of alpha 1-PI and elastase when the preformed complex is added to the same GSH/GSSG or cys/cysSScys redox buffers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420175 TI - Spontaneous transfer of ganglioside GM1 from its micelles to lipid vesicles of differing size. AB - The spontaneous incorporation of II3-N-acetylneuraminosylgangliotetraosylceramide (GM1) from its micelles into phospholipid bilayer vesicles has been investigated to determine whether curvature-induced changes in membrane lipid packing influence ganglioside uptake. Use of conventional liquid chromatography in conjunction with technically-improved molecular sieve gels permits ganglioside micelles to be separated from phospholipid vesicles of different average size including vesicles with diameters smaller than 40 nm and, thus, allows detailed study of native ganglioside GM1 incorporation into model membranes under conditions where complicating processes like fusion are readily detected if present. At 45 degrees C, the spontaneous transfer rate of GM1 from its micelles to small unilamellar vesicles (SUVs) comprised of 1-palmitoyl-2-oleoyl-sn-glycero 3-phosphocholine (POPC) is at least 3-fold faster than that to similar composition large unilamellar vesicles (LUVs) prepared by octyl glucoside dialysis. Careful analysis of ganglioside GM1 distribution among vesicle populations of differing average size reveals that GM1 preferentially incorporates into the smaller vesicles of certain populations. This behavior is observed in SUVs as well as in LUV-SUV mixtures and actually serves as a sensitive indicator for the presence of trace quantities of SUVs in various LUV preparations. Analysis of the results shows that both differences in the diffusional collision frequency between GM1 monomers and either SUVs or LUVs and curvature-induced changes in the interfacial lipid packing in either SUVs or LUVs can dramatically influence spontaneous ganglioside uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420176 TI - Standard thermodynamic formation properties for the adenosine 5'-triphosphate series. AB - The criterion for chemical equilibrium at specified temperature, pressure, pH, concentration of free magnesium ion, and ionic strength is the transformed Gibbs energy, which can be calculated from the Gibbs energy. The apparent equilibrium constant (written in terms of the total concentrations of reactants like adenosine 5'-triphosphate, rather than in terms of species) yields the standard transformed Gibbs energy of reaction, and the effect of temperature on the apparent equilibrium constant at specified pressure, pH, concentration of free magnesium ion, and ionic strength yields the standard transformed enthalpy of reaction. From the apparent equilibrium constants and standard transformed enthalpies of reaction that have been measured in the adenosine 5'-triphosphate series and the dissociation constants of the weak acids and magnesium complexes involved, it is possible to calculate standard Gibbs energies of formation and standard enthalpies of formation of the species involved at zero ionic strength. This requires the convention that the standard Gibbs energy of formation and standard enthalpy of formation for adenosine in dilute aqueous solutions be set equal to zero. On the basis of this convention, standard transformed Gibbs energies of formation and standard transformed enthalpies of formation of adenosine 5'-trisphosphate, adenosine 5'-diphosphate, adenosine 5'-monophosphate, and adenosine at 298.15 K, 1 bar, pH = 7, a concentration of free magnesium ions of 10(-3) M, and an ionic strength of 0.25 M have been calculated. PMID- 1420177 TI - Analysis by mutagenesis of the ATP binding site of the gamma subunit of skeletal muscle phosphorylase kinase expressed using a baculovirus system. AB - Active gamma subunit of skeletal muscle phosphorylase kinase has been obtained by expression of the rat soleus cDNA in a baculovirus system. The protein exhibited the expected pH 6.8/8.2 activity ratio of 0.6, and its activity was insensitive to Ca2+ addition, indicating that it was free gamma subunit and not a gamma subunit-calmodulin complex. It was stimulated approximately 2-fold by Ca(2+) calmodulin addition, demonstrating that it had retained high-affinity calmodulin binding. By site-directed mutagenesis, we have examined the role of six of the amino acids that constitute the consensus ATP binding site of the protein kinase, which in the gamma subunit is represented by the sequence 26Gly.Arg.Gly.Val.Ser.Ser.Val.Val33. Changes were evaluated by the kinetic determination of the dissociation constants of gamma-ATP, gamma-ADP, gamma AMP.PCP, and gamma-phosphorylase and the maximum catalytic activity. The mutants Ser26-gamma, Ser29-gamma, Phe30-gamma, and Gly31-gamma each exhibited an essentially identical dissociation constant for gamma subunit phosphorylase, indicating that these mutations had not caused a global alteration in the protein structure but were limited to changes in the nucleotide binding site domain. Substitution of either Val33 (by Gly) or Gly28 (by Ser), two of the most conserved residues in all protein kinases, resulted in enzyme with marginally detectable activity. In noted contrast, the Ser26 mutant, which substituted the first glycine of the consensus glycine trio motif, and which is also very highly conserved, retained at least 25% of the enzymatic activity. The Gly31 substitution, which restored a glycine to a position characteristic for most protein kinases, had little overall effect upon the maximum rate of catalysis. Restoration of Ser30 to the more typical phenylalanine, which is present in most protein kinases, had minimal effect on catalysis. These data provide the first direct evaluation of the roles that different residues play within this consensus glycine trio/valine motif of the protein kinases, which up to now have only been surmised to be of importance because of their conservation. Two unexpected findings are that for one residue that is very conserved (Gly26) there is some flexibility of substitution not apparent from the evolutionary conservation and that a second quite conserved residue in protein kinases (equivalent to Gly at position 31) does not produce a protein optimized for nucleotide binding. PMID- 1420178 TI - Structure and novel exons of the human tau gene. AB - The microtubule-binding protein tau is important in establishing and maintaining neuronal morphology and is a major component of the neurofibrillary tangles (NFTs) characteristic of Alzheimer's brain. The neuron-specific tau transcript undergoes complex alternative splicing. The human tau gene has been cloned and mapped. The restriction analysis and partial sequencing of the gene shows that it contains (1) four alternatively spliced exons previously described in rodent and bovine but not in human tau cDNAs and (2) two CpG islands, one associated with the promoter region, the other with exon 9. Examination of human tau mRNA indicates that the human cerebrocortical splicing pattern differs from that previously reported for the murine and bovine tau mRNAs, despite conserved exon organization in all three genes. PMID- 1420179 TI - Effects of magnesium ion on the interaction of atrial muscarinic acetylcholine receptors and GTP-binding regulatory proteins. AB - Muscarinic acetylcholine receptors (mAChR) purified from porcine atrium were reconstituted into lipid vesicles with GTP-binding regulatory proteins (G proteins, Gi, Go, or Gn) purified from porcine cerebrum. Apparent affinities of the reconstituted mAChR and G proteins for carbachol and GDP, respectively, were estimated from the effects of these ligands on the binding of [3H]-L quinuclidinyl benzilate ([3H]QNB) to mAChR and [35S]guanosine 5'-O-(3 thiotriphosphate) ([35S]GTP gamma S) to G proteins in the presence of different concentrations of MgCl2. A total of 30-35% of reconstituted mAChRs exhibited low affinity for carbamylcholine, irrespective of the presence or absence of guanine nucleotides, and the remainder of the mAChRs showed high affinities for carbamylcholine in the absence of GTP or GDP and a low affinity in their presence. The affinity for carbamylcholine in the absence of guanine nucleotides, but not in their presence, increased with increases in MgCl2 concentration. Apparent Kd's for carbamylcholine were estimated to be approximately 100 microM in the presence of guanine nucleotides, 1.5 microM in the absence of guanine nucleotide and Mg2+ (< 0.1 microM), and 0.1 microM in the absence of guanine nucleotide and the presence of MgCl2 (10 mM). These results indicate that mAChRs may assume at least three different conformations that are characterized by different affinities for agonists. Furthermore, the data suggest that MgCl2 is not necessary for the formation of the mAChR-G protein complex, but can induce a conformational change in the complex. On the other hand, the presence of MgCl2 was necessary for carbamylcholine to influence the binding of guanine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420180 TI - Laminins and other strange proteins. AB - Laminins are large multidomain proteins of the extracellular matrix (ECM) with important functions in the development and maintenance of cellular organization and supramolecular structure, in particular in basement membranes. Each molecule is composed of three polypeptide chains, A (300-400 kDa) and B1 and B2 (180-200 kDa), which together form the characteristic cross-shaped laminin structure with three short arms and one long arm. Many different domains have been identified in laminin by sequence analysis, structural investigations, and functional studies. Each short arm is formed by homologous N-terminal portions of one of the three chains. Structurally, each short arm contains two or three globular domains which are connected by rows of manyfold-repeated Cys-rich "EGF-like" domains. In all three chains this region is followed by a long heptad repeat region similar to those found in many alpha-helical coiled-coil proteins. These parts of the three laminin chains constitute a triple-stranded coiled-coil domain, which forms the extended rodlike structure of the long arm. This is the only domain in the protein which is made up of more than one chain and consequently serves the function of chain assembly. The two B chains are terminated by the coiled-coil domain, but the A chain contains an additional C-terminal segment which accounts for five globular domains located at the tip of the long arm. Several important functions of laminin have been assigned to individual domains in either the short arms or terminal regions of the long arm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420181 TI - Crystallographic evidence of a large ligand-induced hinge-twist motion between the two domains of the maltodextrin binding protein involved in active transport and chemotaxis. AB - The periplasmic maltodextrin binding protein of Escherichia coli serves as an initial receptor for the active transport of and chemotaxis toward maltooligosaccharides. The three-dimensional structure of the binding protein complexed with maltose has been previously reported [Spurlino, J. C., Lu, G.-Y., & Quiocho, F. A. (1991) J. Biol. Chem. 266, 5202-5219]. Here we report the structure of the unliganded form of the binding protein refined to 1.8-A resolution. This structure, combined with that for the liganded form, provides the first crystallographic evidence that a major ligand-induced conformational change occurs in a periplasmic binding protein. The unliganded structure shows a rigid-body "hinge-bending" between the two globular domains by approximately 35 degrees, relative to the maltose-bound structure, opening the sugar binding site groove located between the two domains. In addition, there is an 8 degrees twist of one domain relative to the other domain. The conformational changes observed between this structure and the maltose-bound structure are consistent with current models of maltose/maltodextrin transport and maltose chemotaxis and solidify a mechanism for receptor differentiation between the ligand-free and ligand-bound forms in signal transduction. PMID- 1420182 TI - Structure of d(T)n.d(A)n.d(T)n: the DNA triple helix has B-form geometry with C2' endo sugar pucker. AB - The polynucleotide helix d(T)n.d(A)n.d(T)n is the only deoxypolynucleotide triple helix for which a structure has been published, and it is generally assumed as the structural basis for studies of DNA triplexes. The helix has been assigned to an A-form conformation with C3'-endo sugar pucker by Arnott and Selsing [1974; cf. Arnott et al. (1976)]. We show here by infrared spectroscopy in D2O solution that the helix is instead B-form and that the sugar pucker is in the C2'-endo region. Distamycin A, which binds only to B-form and not to A-form helices, binds to the triple helix without displacement of the third strand, as demonstrated by CD spectroscopy and gel electrophoresis. Molecular modeling shows that a stereochemically satisfactory structure can be build using C2'-endo sugars and a displacement of the Watson-Crick base-pair center from the helix axis of 2.5 A. Helical constraints of rise per residue (h = 3.26 A) and residues per turn (n = 12) were taken from fiber diffraction experiments of Arnott and Selsing (1974). The conformational torsion angles are in the standard B-form range, and there are no short contacts. In contrast, we were unable to construct a stereochemically allowed model with A-form geometry and C3'-endo sugars. Arnott et al. (1976) observed that their model had short contacts (e.g., 2.3 A between the phosphate dependent oxygen on the A strand and O2 in the Hoogsteen-paired thymine strand) which are generally known to be outside the allowed range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420183 TI - Isotope-edited nuclear magnetic resonance study of Fv fragment of anti-dansyl mouse monoclonal antibody: recognition of the dansyl hapten. AB - An isotope-edited proton nuclear magnetic resonance study is reported of Fv, which is the smallest antigen recognition unit composed of VH and VL domains. Fv has been obtained by clostripain digestion of a short-chain anti-dansyl mouse IgG2a monoclonal antibody [Igarashi, T., Sato, M., Katsube, Y., Takio, K., Tanaka, T., Nakanishi, M., & Arata, Y. (1990) Biochemistry 29, 5727-5733]. A variety of stable-isotope-labeled anti-dansyl Fv analogues have been prepared. The aromatic proton resonances for all Tyr residues of the Fv fragment have been assigned in the absence and presence of epsilon-dansyl-L-lysine by means of isotope-edited homonuclear and heteronuclear two-dimensional NMR experiments. On the basis of the established assignments, it has been concluded that the dansyl ring is bound through Tyr-96H and Tyr-104H to both ends of H3, the third hypervariable region of the heavy chain. We also suggest that the antigen binding results in the formation of a hydrophobic core comprising the dansyl ring and the aromatic rings of Tyr-96H and Tyr-104H. PMID- 1420184 TI - A beta-turn is present in the 392-411 segment of the human fibrinogen gamma chain. Effects of structural changes in this segment on affinity to antibody 4A5. AB - The interaction between fibrinogen gamma-peptide 392-411, LTIGEGQQHHLGGAKQAGDV, and monoclonal antibody 4A5, an antibody with a high affinity for both for the peptide and native fibrinogen, is being studied as a model for peptide-antibody interaction. Two-dimensional NMR studies of the free peptide at pH 5.2 indicated the presence of a significant population, about 60%, of type II beta-turn, spanning residues Gln407-Asp410. At pH 2.7, little, if any, turn structure is present. The D-Ala409 analog, which, for steric reasons, would be expected to preserve the beta-turn, and the L-Ala409 analog, which would not be expected to have this conformational feature, were synthesized, and NMR studies confirmed the respective structural predictions. The affinity of the D-Ala analog for antibody 4A5 is even greater than that displayed by native gamma 392-411, while the affinity of the L-Ala analog is less than one-tenth that of the native peptide. Both conformational and steric effects involving residues 407-410 may be important in recognition by antibody 4A5. Since gamma 392-411 includes a platelet receptor binding locus of fibrinogen, and this and related peptides are inhibitors of platelet aggregation, the D-Ala409 and L-Ala409 analogs were tested for platelet binding. Neither of the analogs displays any measurable platelet binding, indicating that the recognition requirements for the platelet receptor differ considerably from those for antibody 4A5. PMID- 1420185 TI - A differential scanning calorimetric study of the thermal unfolding of mutant forms of phage T4 lysozyme. AB - In continuation of our earlier work on the effects of amino acid replacements on the thermodynamics of the thermal unfolding of T4 lysozyme [Kitamura, S., & Sturtevant, J. M. (1989) Biochemistry 28, 3788-3792; Connelly, P., Ghosaini, L., Hu, C.-Q., Kitamura, S., Tanaka, A., & Sturtevant, J. M. (1991) Biochemistry 30, 1887-1891; Hu, C.-Q., Kitamura, S., Tanaka, A., & Sturtevant, J. M. (1992) Biochemistry 31, 1643-1647], we report here a study by differential scanning calorimetry of the effects of five replacements at Ile3. Four of these replacements, those with Glu, Phe, Pro, and Thr, caused apparent destabilizations, while the replacement by Leu led to a small apparent stabilization. The largest observed destabilization (Ile3Pro) amounted to -3.0 kcal mol-1 in free energy at pH 2.00 and 38.8 degrees C (the denaturational temperature of the wild-type protein at this pH), and the largest stabilization amounted to +1.2 kcal mol-1 at pH 3.00 and 53.6 degrees C. PMID- 1420188 TI - 1-N-glycyl beta-oligosaccharide derivatives as stable intermediates for the formation of glycoconjugate probes. AB - Incubation of reducing sugars in ammonium bicarbonate was found to be a simple procedure for the formation of beta-D-glycosylamines of purified complex oligosaccharides in 70-80% yield. These provide valuable intermediates for the synthesis of a wide range of oligosaccharide probes and derivatives by acylation of the 1-amino function. The 1-amino function showed different rates of reactivity with different reagents. In general, interactions with large ring systems such as the fluorophores dansyl chloride and carboxyfluorescein gave 10 20% yields of products, which consisted of mixtures of both anomeric forms, whereas smaller acylating reagents gave near-quantitative yields of the desired beta-D-derivatives. Steric effects may explain differences in reactivity. N Chloroacetamido derivatives could be obtained in high yield with retention of the beta-anomeric configuration. Subsequent ammonolysis of the chloroacetamido function afforded the corresponding N-glycyl beta-derivatives. The linker thereby introduced retains the amino function, possesses the useful properties of fixed anomeric configuration, improved stability, and uniform reactivity with a variety of reagents, and is structurally analogous to an asparagine side chain. The potential therefore exists for the generation of oligosaccharide derivatives tailored for different applications. PMID- 1420187 TI - Fibril formation by primate, rodent, and Dutch-hemorrhagic analogues of Alzheimer amyloid beta-protein. AB - Deposition of extraneuronal fibrils that assemble from the 39-43 residue beta/A4 amyloid protein is one of the earliest histopathological features of Alzheimer's disease. We have used negative-stain electron microscopy, Fourier-transform infrared (FT-IR) spectroscopy, and fiber X-ray diffraction to examine the structure and properties of synthetic peptides corresponding to residues 1-40 of the beta/A4 protein of primate [Pm(1-40); human and monkey], rodent [Ro(1-40); with Arg5-->Gly, Tyr10-->Phe, and His13-->Arg], and hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) [Du(1-40); with Glu22- >Gln]. As controls, we examined a reverse primate sequence [Pm*(40-1)] and an extensively substituted primate peptide [C(1-40); with Glu3-->Arg, Arg5-->Glu, Asp7-->Val, His13-->Lys, Lys16-->His, Val18-->Asp, Phe19-->Ser, Phe20-->Tyr, Ser26-->Pro, Ala30-->Val, Ile31-->Ala, Met35-->norLeu, Gly38-->Ile, Val39-->Ala, and Val40-->Gly]. The assembly of these peptides was studied to understand the relationship between species-dependent amyloid formation and beta/A4 sequence and the effect of a naturally occurring point mutation of fibrillogenesis. The three N-terminal amino acid differences between Pm(1-40) and Ro(1-40) had virtually no effect on the morphology or organization of the fibrils formed by these peptides, indicating that the lack of amyloid deposits in rodent brain is not due directly to specific changes in its beta/A4 sequence. beta-Sheet and fibril formation, judged by FT-IR, was maximal within the pH range 5-8 for Pm(1-40), pH 5-10.5 for Du(1-40), and pH 2.5-8 for Ro(1-40).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420189 TI - Synthesis of 1-N-glycyl beta-oligosaccharide derivatives. Reactivity of Lens culinaris lectin with a fluorescent labeled streptavidin pseudoglycoprotein and immobilized neoglycolipid. AB - The lectin from Lens culinaris (lentil) has a binding specificity for glycopeptides bearing 6-O-linked fucose on the reducing terminus on complex-type N-linked oligosaccharides. Lentil lectin therefore provides an excellent example of a carbohydrate binding protein in which high-affinity interactions are dependent on the integrity of the oligosaccharide core structure. We report here the synthesis of the 1-N-glycyl beta-derivative of Gal beta 4GlcNAc beta 2Man alpha 6(Gal beta 4GlcNAc beta 2Man alpha 3)Man beta 4GlcNAc beta 4(Fuc alpha 6) GlcNAc (Gal-2F) and its subsequent biotinylation and palmitoylation. The biotin derivative when bound to a streptavidin-fluorescein isothiocyanate (FITC) conjugate was able to bind to both concanavalin A (ConA) and lentil lectin affinity columns. In contrast, synthesis of the biotin derivative of the glycamine derivative of Gal-2F and subsequent binding to streptavidin-FITC afforded reactivity to a ConA affinity column but not to a lentil lectin affinity column. Lentil lectin also bound to plastic microtiter plates containing the adsorbed palmitoyl-1-N-glycyl beta-derivative. No binding occurred when the homologous glycamine neoglycolipid was used. These results suggest the 1-N-glycyl beta-derivative of oligosaccharides may have general utility as an intermediate in the synthesis of novel glycoconjugate probes. PMID- 1420186 TI - Picosecond phase grating spectroscopy of hemoglobin and myoglobin: energetics and dynamics of global protein motion. AB - Phase grating spectroscopy has been used to follow the optically triggered tertiary structural changes of carboxymyoglobin (MbCO) and carboxyhemoglobin (HbCO). Probe wavelength and temperature dependencies have shown that the grating signal arises from nonthermal density changes induced by the protein structural changes. The material displaced through the protein structural changes leads to the excitation of coherent acoustic modes of the surrounding water. The coupling of the structural changes to the fluid hydrodynamics demonstrates that a global change in the protein structure is occurring in less than 30 ps. The global relaxation is on the same time scale as the local changes in structure in the vicinity of the heme pocket. The observed dynamics for global relaxation and correspondence between the local and global structural changes provides evidence for the involvement of collective modes in the propagation of the initial tertiary conformational changes. The energetics can also be derived from the acoustic signal. For MbCO, the photodissociation process is endothermic by 21 +/- 2 kcal/mol, which corresponds closely to the expected Fe-CO bond enthalpy. In contrast, HbCO dissipates approximately 10 kcal/mol more energy relative to myoglobin during its initial tertiary structural relaxation. The difference in energetics indicates that significantly more energy is stored in the hemoglobin structure and is believed to be related to the quaternary structure of hemoglobin not present in the monomeric form of myoglobin. These findings provide new insight into the biomechanics of conformational changes in proteins and lend support to theoretical models invoking stored strain energy as the driving force for large amplitude correlated motions. PMID- 1420190 TI - Complete structure of the adhesin receptor polysaccharide of Streptococcus oralis ATCC 55229 (Streptococcus sanguis H1). AB - This report describes the determination of the complete primary structure of the adhesin receptor polysaccharide of Streptococcus oralis ATCC 55229 (previously characterized as Streptococcus sanguis H1), a Gram-positive bacteria implicated in dental plaque formation. The polysaccharide was isolated from S. oralis ATCC 55229 cells after deproteination, enzymatic hydrolysis, and ion exchange chromatography. It was shown to consist of rhamnose, galactose, glucose, glycerol, and phosphate, in molar ratios of 2:3:1:1:1. Sequence and linkage assignments of the glycosyl residues were obtained by methylation analysis followed by gas-liquid chromatography and electron-impact mass spectrometry. 31P NMR spectroscopy revealed that phosphate was present in a diester, connecting glycerol to one of the galactosyl residues. High-performance liquid chromatography of a partial acid hydrolysate of the polysaccharide confirmed this finding by showing galactose 6-phosphate and glycerol 1-phosphate. The structural determination was completed by the combination of two-dimensional homonuclear Hartmann-Hahn and NOE experiments and heteronuclear [1H,13C] and [1H,31P] multiple-quantum coherence experiments. Thus, the adhesin receptor polysaccharide of S. oralis ATCC 55229 was found to be a polymer composed of hexasaccharide repeating units that contain glycerol linked through a phosphodiester to C6 of the alpha-galactopyranosyl residue and are joined end-to-end through galactofuranosyl-beta(1-->3)-rhamnopyranosyl linkages: [formula: see text] This structure is novel among bacterial cell surface polysaccharides in general and specifically among those implicated in dental plaque formation. PMID- 1420191 TI - Cloning, sequencing, and expression in Escherichia coli of the Clostridium tetanomorphum gene encoding beta-methylaspartase and characterization of the recombinant protein. AB - The gene encoding methylaspartase (EC 4.3.1.2) from Clostridium tetranomorphum has been cloned, sequenced, and expressed in Escherichia coli. The open reading frame (ORF) codes for a polypeptide of 413 amino acid residues (M(r) 45,539) of which seven are cysteine residues. The size of the ORF indicates that methylaspartase is a homodimer rather than an (AB)2 tetramer. The deduced primary structure of the protein shows no homology to enzymes that catalyze similar reactions or, indeed, any convincing homology with any other characterized protein. The recombinant protein is identical to the enzyme isolated directly from C. tetanomorphum as determined by several criteria. The enzyme is obtained in a highly active form (approximately 70% of the activity of the natural enzyme) and migrates as a single band (M(r) 49,000) in SDS-polyacrylamide gels. The kinetic parameters for the deamination of (2S,3S)-3-methylaspartic acid by the natural and recombinant proteins are very similar, and the proteins display identical potassium ion-dependent primary deuterium isotope effects for V and V/K when (2S,3S)-3-methylaspartic acid is employed as the substrate. In accord with the activity of the natural enzyme, the recombinant protein is able to catalyze the slow formation of (2S,3R)-3-methylaspartic acid, the L-erythro-epimer of the natural substrate, from mesaconic acid and ammonia. Earlier work in which the cysteine residues in the protein were labeled with N-ethylmaleimide had indicated that there were eight cysteine residues per protein monomer. One cysteine residue was protected by substrate. Here evidence is forwarded to suggest that the residue that was protected by the substrate is not a cysteine residue but the translation product of a serine codon. Kinetic data indicate that this serine residue may be modified in the active enzyme. The implications of these findings on the mechanism of catalysis are discussed within the context of a few emerging mode of action for methylaspartate ammonia-lyase. PMID- 1420192 TI - Mechanistic studies on the human matrix metalloproteinase stromelysin. AB - To probe the mechanism of stromelysin (SLN)-catalyzed peptide hydrolysis, we determined the pH dependence of kc/Km and solvent deuterium isotope effects on kc and kc/Km. pH dependencies of kc/Km were determined for the SLN-catalyzed hydrolysis of three peptides: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Nle-NH2,Arg Pro-Ala-Pro-Gln-Gln- Phe-Phe - Gly-Leu-NleNH2, and N-acetyl-Arg-Pro-Ala-Pro-Gln Gln-Phe-Phe-Gly-Leu-Nle-NH2 (cleavage at Gln-Phe bond). The pH dependencies are all bell-shaped with shoulders that extend from pH 7.5 to 8.5. The existence of a shoulder indicates that the reaction mechanism involves at least two routes to products. These curves are governed by three proton ionizations with pKa values of 5.4, 6.1, and 9.5. The solvent isotope effect measurements provided the following values: D(kc/Km) = 0.80 +/- 0.05 and D(kc) = 1.58 +/- 0.05. That D(kc/Km) and D(kc) are different suggests that the rate-limiting transition states for the processes governed by kc/Km and kc cannot be the same. We use these results, together with analogy to thermolysin catalysis, to develop a mechanism for SLN catalysis. PMID- 1420193 TI - Haloperoxidase activity of Phanerochaete chrysosporium lignin peroxidases H2 and H8. AB - Monochlorodimedone (MCD), commonly used as a halogen acceptor for haloperoxidase assays, was oxidized by hydrogen peroxide in the presence of lignin peroxidase isoenzymes H2 and H8. When oxidized, it produced a weak absorption band with an intensity that varied with pH. This absorbance was used as a simple method for the product analysis because it disappeared when MCD was brominated or chlorinated. We assessed the activity of the lignin peroxidases for oxidation of bromide by measuring the bromination of MCD, the formation of tribromide, the bromide-mediated oxidation of glutathione, and the bromide-mediated catalase-like activity. We analyzed the reaction products of MCD and the halide-mediated oxidation of glutathione when bromide was replaced by chloride. These enzymes demonstrated no significant activity for oxidation of chloride. Unlike other peroxidases, the lignin peroxidases exhibited similar pH-activity curves for the iodide and bromide oxidations. The optimum pH for activity was about 2.5. Surprisingly, this pH dependence of lignin peroxidase activity for the halides was nearly the same in the reactions with hydrogen donors, such as hydroquinone and guaiacol. The results suggested that protonation of the enzymes with pKa approximately 3.2 is necessary for the catalytic function of lignin peroxidases, irrespective of whether the substrates are electron or hydrogen donors. These unique reaction profiles of lignin peroxidases are compared to those of other peroxidases, such as lactoperoxidase, bromoperoxidase, chloroperoxidase, and horseradish peroxidase. Isozyme H2 was more active than isozyme H8, but isozyme H8 was more stable at very acidic pH. PMID- 1420194 TI - Cleavage of the Lys196-Ser197 bond of prolyl oligopeptidase: enhanced catalytic activity for one of the two active enzyme forms. AB - Prolyl oligopeptidase, a representative of a new family of serine proteases, is remarkably sensitive to ionic strength and has two catalytically active forms, which interconvert with changing pH [Polgar, L. (1991) Eur. J. Biochem. 197, 441 447]. To reveal whether conformational changes are associated with these effects, prolyl oligopeptidase was digested with trypsin. SDS gel electrophoresis studies demonstrated that tryptic digestion of the 75-kDa native protein generated two fragments, one having a molecular mass of 51 kDa and the other of 26 kDa. The digestion was markedly dependent on the ionic strength. Specifically, the digestion proceeded more rapidly in 0.05 M Hepes buffer than in 0.05 M Hepes buffer containing 0.5 M NaCl. Moreover, the nicked enzyme formed at low ionic strength was not stable but degraded and inactivated during an extended incubation. The digestion experiments suggested that alteration in the ionic strength elicits conformational changes in native prolyl oligopeptidase, and this may account for the enhanced catalytic activity observed at higher ionic strength. The two fragments of the nicked prolyl oligopeptidase did not separate during size-exclusion chromatography under nondenaturing conditions on a Superose 12 column and eluted in place of the native enzyme, indicating that they were strongly associated. The reactive serine residues of the nicked enzyme was labeled with tritiated diisopropyl phosphofluoridate, and the fragments were separated by size-exclusion chromatography in urea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420197 TI - Enhanced stability of histone octamers from plant nucleosomes: role of H2A and H2B histones. AB - Gel filtration and sedimentation studies have previously established that the vertebrate animal core histone octamer is in equilibrium with an (H3-H4)2 tetramer and an H2A-H2B dimer [Eickbush, T. H., & Moudrianakis, E. N. (1978) Biochemistry 17, 4955-4964; Godfrey, J. E., Eickbush, T. H., & Moudrianakis, E. N. (1980) Biochemistry 19, 1339-1346]. We have investigated the core histone octamer of wheat (Triticum aestivum L.) and have found it to be much more stable than its vertebrate animal counterpart. When vertebrate animal histone octamers are subjected to gel filtration in 2 M NaCl, a trailing peak of H2A-H2B dimer can be clearly resolved from the main octamer peak. When the plant octamer is subjected to the identical procedure, there is no trailing peak of H2A-H2B dimer, but rather a single peak containing the octamer. A sampling across the octamer peak from leading to trailing edge shows no change in the ratio of H2A-H2B to (H3 H4)2. Surprisingly, the plant octamer shows the same stability at 0.6 M NaCl, a salt concentration in which the vertebrate animal octamer dissociates into dimers and tetramers. Equilibrium sedimentation data indicate that the assembly potential of the wheat histones in 2 M NaCl is very high at all protein concentrations above 0.1 mg mL-1. In order to disrupt the forces stabilizing the plant histone octamer at high histone concentrations, the concentration of NaCl must be lowered to approximately 0.3 M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420196 TI - DNA recognition and binding by the Euplotes telomere protein. AB - The 51-kDa telomere protein from Euplotes crassus binds to the extreme terminus of macronuclear telomeres, generating a very salt-stable telomeric DNA-protein complex. The protein recognizes both the sequence and the structure of the telomeric DNA. To explore how the telomere protein recognizes and binds telomeric DNA, we have examined the DNA-binding specificity of the purified protein using oligonucleotides that mimic natural and mutant versions of Euplotes telomeres. The protein binds very specifically to the 3' terminus of single-stranded oligonucleotides with the sequence (T4G4) > or = 3 T4G2; even slight modifications to this sequence reduce binding dramatically. The protein does not bind oligonucleotides corresponding to the complementary C4A4 strand of the telomere or to double-stranded C4A4.T4G4-containing sequences. Digestion of the telomere protein with trypsin generates an N-terminal protease-resistant fragment of approximately 35 kDa. This 35-kDa peptide appears to comprise the DNA-binding domain of the telomere protein as it retains most of the DNA-binding characteristics of the native 51-kDa protein. For example, the 35-kDa peptide remains bound to telomeric DNA in 2 M KCl. Additionally, the peptide binds well to single-stranded oligonucleotides that have the same sequence as the T4G4 strand of native telomeres but binds very poorly to mutant telomeric DNA sequences and double-stranded telomeric DNA. Removal of the C-terminal 15 kDa from the telomere protein does diminish the ability of the protein to bind only to the terminus of a telomeric DNA molecule. PMID- 1420195 TI - Characterization of dipyridophenazine complexes of ruthenium(II): the light switch effect as a function of nucleic acid sequence and conformation. AB - Spectroscopic parameters for two novel ruthenium complexes on binding to nucleic acids of varying sequences and conformations have been determined. These complexes, Ru(bpy)2dppz2+ and Ru(phen)2dppz2+ (bpy = 2,2'-bipyridine; phen = 1,10 phenanthroline; dppz = dipyrido[3,2:a-2',3':c]-phenazine) serve as "molecular light switches" for DNA, displaying no photoluminescence in aqueous solution but luminescing intensely in the presence of DNA. The luminescent enhancement observed upon binding is attributed to the sensitivity of the excited state to quenching by water; in DNA, the metal complex, upon intercalation into the helix, is protected from the aqueous solvent, thereby preserving the luminescence. Correlations between the extent of protection (depending upon the DNA conformation) and the luminescence parameters are observed. Indeed, the strongest luminescent enhancement is observed for intercalation into DNA conformations which afford the greatest amount of overlap with access from the major groove, such as in triple helices. Differences are observed in the luminescent parameters between the two complexes which also correlate with the level of water protection. In the presence of nucleic acids, both complexes exhibit biexponential decays in emission. Quenching studies are consistent with two intercalative binding modes for the dppz ligand from the major groove: one in which the metal-phenazine axis lies along the DNA dyad axis and another where the metal-phenazine axis lies almost perpendicular to the DNA dyad axis. Ru(bpy)2dppz2+ and Ru(phen)2dppz2+ are shown here to be unique reporters of nucleic acid structures and may become valuable in the design of new diagnostics for DNA. PMID- 1420200 TI - Analysis of human red cell spectrin tetramer (head-to-head) assembly using complementary univalent peptides. AB - The mass-driven assembly of spectrin dimers to form tetramers involves two equal head-to-head alpha-beta associations and requires at least 30 degrees C for interconversion to occur readily. In this paper, the properties of tetramer formation were investigated using two complementary univalent peptides (the alpha I domain and beta monomers). Since the alpha I domain lacks an essential nucleation site required for side-to-side (lateral) heterodimer assembly [Speicher et al. (1992) J. Biol. Chem. 267, 14775-14782], these two peptides can only assemble head-to-head at a single site. This head-to-head assembly readily occurs at lower temperatures, indicating the temperature barrier for dimer tetramer interconversion is caused by a conformational constraint of the dimer. This constraint, a closed hairpin loop, is released when the laterally associated partner is removed. The univalent alpha I-beta binding affinity at 37 degrees C (Ka = 1.4 x 10(5) M-1) is similar to the dimer-tetramer association constant at the same temperature. As the temperature is decreased from 37 to 0 degrees C, the alpha I-beta binding affinity increases about 32-fold. In contrast with head-to head associations involving dimers, the second-order rate constants of two complementary univalent peptides (i.e., alpha I and beta) are dramatically higher, and the estimated activation energy (about 50 kJ mol-1) is about 5-fold lower. An open dimer conformation is an obligatory high-energy intermediate required for dimer-tetramer interconversion, and opening the dimer hairpin loop contributes about 190 kJ mol-1 to the activation energy for tetramer association.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420198 TI - Probing the primary donor environment in the histidineM200-->leucine and histidineL173-->leucine heterodimer mutants of Rhodobacter capsulatus by light induced Fourier transform infrared difference spectroscopy. AB - Light-induced P+QB-/PQB FTIR difference spectra of reaction centers (RCs) have been obtained from chromatophores lacking light-harvesting B800-850 antenna for Rhodobacter capsulatus wild type (WT) and for the two mutants HisM200-->Leu and HisL173-->Leu. The primary donor (P) in both mutants consists of a bacteriochlorophyll-bacteriopheophytin heterodimer. The most prominent difference between the WT and the mutant spectra is in the 1600-1200-cm-1 region. The WT spectrum displays large positive bands at approximately 1290, 1500-1430, and 1580 1530 cm-1. These three bands are either small or altogether absent in the heterodimer spectra. In addition, both heterodimer spectra compare well with the electrochemically generated BChla+/BChla spectrum [Mantele, W.G., Wollenweber, A. M., Nabedryk, E., & Breton, J. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 8468 8472]. These observations indicate that the positive charge is localized on the monomeric BChl in the heterodimers. The overall shape of the ester and keto C = O signals in the BChla+/BChla spectrum is maintained in the in situ spectra although significant differences are observed in the frequency, width, and splitting of the bands. The shape of the signal at 1757/1744 cm-1 in HisL173- >Leu is comparable to the 1751/1737-cm-1 signal of BChla+/BChla in tetrahydrofuran, indicating a free 10a ester C = O of PM in HisL173-->Leu. The reduced amplitude of the negative 1740-cm-1 feature in both HisM200-->Leu and WT spectra suggests a hydrogen-bonded 10a ester C = O for PL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420199 TI - Role of the carboxy terminus of polypeptide D1 in the assembly of a functional water-oxidizing manganese cluster in photosystem II of the cyanobacterium Synechocystis sp. PCC 6803: assembly requires a free carboxyl group at C-terminal position 344. AB - The D1 polypeptide of the photosystem II (PSII) reaction center is synthesized as a precursor polypeptide which is posttranslationally processed at the carboxy terminus. It has been shown in spinach that such processing removes nine amino acids, leaving Ala344 as the C-terminal residue [Takahashi, M., Shiraishi, T., & Asada, K. (1988) FEBS Lett. 240, 6-8; Takahashi, Y., Nakane, H., Kojima, H., & Satoh, K. (1990) Plant Cell Physiol. 31, 273-280]. We show here that processing on the carboxy side of Ala344 also occurs in the cyanobacterium Synechocystis 6803, resulting in the removal of 16 amino acids. By constructing a deletion strain of Synechocystis 6803 that lacks the three copies of the psbA gene encoding D1, we have developed a system for generating psbA mutants. Using this system, we have constructed mutants of Synechocystis 6803 that are modified in the region of the C-terminus of the D1 polypeptide. Characterization of these mutants has revealed that (1) processing of the D1 polypeptide is blocked when the residue after the cleavage site is changed from serine to proline (mutant Ser345Pro) with the result that the manganese cluster is unable to assemble correctly; (2) the C-terminal extension of 16 amino acid residues can be deleted with little consequence either for insertion of D1 into the thylakoid membrane or for assembly of D1 into a fully active PSII complex; (3) removal of only one more residue (mutant Ala344stop) results in a loss of assembly of the manganese cluster; and (4) the ability of detergent-solubilized PSII core complexes (lacking the manganese cluster) to bind and oxidize exogenous Mn2+ by the secondary donor, Z+, is largely unaffected in the processing mutants (the Ser345Pro mutant of Synechocystis 6803 and the LF-1 mutant of Scenedesmus obliquus) and the truncation mutant Ala344stop. Our results are consistent with a role for processing in regulating the assembly of the photosynthetic manganese cluster and a role for the free carboxy terminus of the mature D1 polypeptide in the ligation of one or more manganese ions of the cluster. PMID- 1420201 TI - Amphiphilic forms of butyrylcholinesterase in mucosal cells of rat intestine. AB - The properties of a cholinesterase from mucosal cells of rat intestine have been characterized. The enzyme was identified as butyrylcholinesterase because it was more sensitive to iso-OMPA (IC50 = 1.0 x 10(-6) M) than to BW284C51 (IC50 = 5.5 x 10(-5) M) and was not inhibited by substrate excess. It displayed a higher affinity for acetylthiocholine than for butyrylthiocholine. A major molecular form was observed sedimenting at 5.9 S. Two other minor molecular forms were identified as a hydrophilic tetramer (G4, sedimenting at 10.5 S) and a monomer (G1, sedimenting at 4.3 S). The 5.9 S component was referred to as "G" form (G for globular) and not "G2" as usual dimers for the following reasons: (i) the G form was unaffected by the reducing agents, beta-mercaptoethanol and dithiothreitol, which converted disulfide-linked dimers of acetylcholinesterase into monomers, (ii) the G form was shifted from 5.9 to 3.4 S when the sucrose gradient contained Triton X-100. This value of 3.4 S (in Triton X-100) appeared too low for a typical G2 form. The shift in the S value was partly reversible: the 3.4 S form resedimented at 5.2 S in the absence of detergent. The behavior of the G form in sucrose gradients indicated that it was amphiphilic. This was confirmed in nondenaturing electrophoreses and also by quantitative binding of the G form to octyl-Sepharose. The hydrophobic domain of the G form was not a glycolipid, as shown by its insensitivity to Bacillus thuringiensis phosphatidylinositol-specific phospholipase C and its nonaggregating properties in the absence of nondenaturing detergent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420202 TI - Effects of adenyl nucleotides and carbachol on cooperative interactions among G proteins. AB - Muscarinic agonists and adenyl nucleotides are noncompetitive modulators of sites labeled by [35S]GTP gamma S in washed cardiac membranes from Syrian golden hamsters. Specific binding of the radioligand and its inhibition by either GTP gamma S or GDP reveals three states of affinity for guanyl nucleotides. In the absence of adenyl nucleotide, carbachol promotes an apparent interconversion of sites from higher to lower affinity for GDP; the effect recalls that of guanyl nucleotides on the binding of agonists to muscarinic receptors. In the presence of 0.1 mM ATP gamma S, the binding of [35S]GTP gamma S is increased at concentrations up to about 50 nM and decreased at higher concentrations. At a radioligand concentration of 160 pM, binding exhibits a bell-shaped dependence on the concentration of both ATP gamma S and AMP-PNP; with ADP and ATP, there is a second increase in bound [35S]GTP gamma S at the highest concentrations of adenyl nucleotide. ATP gamma S and AMP-PNP also modulate the effect of GDP, which itself emerges as a cooperative process: that is, binding of the radioligand in the presence of AMP-PNP exhibits a bell-shaped dependence on the concentration of GDP; moreover, the GDP-dependent increase in bound [35S]GTP gamma S is enhanced by carbachol. The interactions among GDP, GTP gamma S, and carbachol can be rationalized quantitatively in terms of a cooperative model involving two sites tentatively identified as G proteins. Both GTP gamma S and GDP exhibit negative homotropic cooperativity; carbachol enhances the homotropic cooperativity of GDP and induces or enhances positive heterotropic cooperativity between GDP and [35S]GTP gamma S. An analogous mechanism may underlie the guanyl nucleotide dependent binding of agonists to muscarinic receptors. The data suggest that the binding properties of G proteins and their associated receptors reflect cooperative effects within heterooligomeric arrays; agonist-induced changes in cooperativity may facilitate the exchange of GTP for bound GDP and thereby constitute the mechanism of G protein activation in vivo. PMID- 1420203 TI - Molecular cloning and characterization of rKlk10, a cDNA encoding T-kininogenase from rat submandibular gland and kidney. AB - We have cloned and determined the nucleotide sequence of a novel kallikrein-like mRNA, designated rKlk10*, from rat submandibular gland and kidney with the aid of the polymerase chain reaction (PCR). This cDNA contains 737 base pairs comprising the sequence encoding a mature protein of 235 amino acid residues, partial zymogen peptide, and 3' noncoding sequence. Sequence comparisons showed that rKlk10 mRNA shares 87 and 88% sequence identity with rat tissue kallikrein at nucleic acid and amino acid levels, respectively. It encodes a 26,428-Da acidic protein whose derived amino acid sequence matches completely with the partial amino acid sequence of a kallikrein-like enzyme designated as T-kininogenase, K10 protein, or antigen-gamma purified from rat submandibular gland [Xiong et al. (1990) J. Biol. Chem. 265, 2822-2827; Gutman et al. (1991) Eur. J. Biochem. 784, 1-5; Berg et al. (1991) Biochem. J. 280, 19-25]. The protein encoded by rKlk10 retains the key amino acid residues determining kallikrein cleavage specificity. Northern blot analysis with an rKlk10-specific oligonucleotide probe showed that its mRNA level in the submandibular gland is decreased dramatically by administration of the beta agonist isoproterenol. Tissue-specific expression of rKlk10 was analyzed by Northern blotting and Southern blotting of PCR-amplified cDNA, which showed that rKlk10 is expressed at high levels in the submandibular gland and low levels in the kidney but not in seven other tissues including prostate, liver, heart, adrenal gland, testes, pituitary, and pancreas. rKlk10 cDNAs cloned from the kidney and submandibular gland show sequence identity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420204 TI - Antibody and peptide probes of interactions between the SH1-SH2 region of myosin subfragment 1 and actin's N-terminus. AB - The negatively charged residues in the N-terminus of actin and the 697-707 region on myosin subfragment 1 (S-1), containing the reactive cysteines SH1 and SH2, are known to be important for actin-activated myosin ATPase activity. The relationship between these two sites was first examined by monitoring the rates of SH1 and SH2 modification with N-ethylmaleimide in the presence of actin and, secondly, by testing for direct binding of SH1 peptides to the N-terminal segment on actin. While actin alone protected SH1 from N-ethylmaleimide modification, this effect was abolished by an antibody against the seven N-terminal amino acids on actin, F(ab)(1-7), and was greatly reduced when the charge of acidic residues at actin's N-terminus was altered by carbodiimide coupling of ethylenediamine. Neither F(ab)(1-7) nor ethylenediamine treatment reversed the effect of F-actin on SH2 reactivity in SH1-modified S-1. These results show a communication between the SH1 region on S-1 and actin's N-terminus in the acto-S-1 complex. To test whether such a communication involves the binding of the SH1 site on S-1 to the N terminal segment of actin, the SH1 peptide IRICRKG-NH2(4+) was used. Cosedimentation experiments revealed the binding of three to six peptides per actin monomer. Peptide binding to actin was affected slightly, if at all, by F(ab)(1-7). The antibody also did not change the polymerization of G-actin by the peptides. The peptides caused a small reduction in the binding of S-1 to actin and did not change the binding of F(ab)(1-7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420205 TI - Alzheimer's disease and control brain contain soluble derivatives of the amyloid protein precursor that end within the beta amyloid protein region. AB - The 39-43 amino acid beta amyloid protein (A beta) that deposits as amyloid in the brains of patients with Alzheimer's disease (AD) is encoded as an internal sequence within a larger membrane-associated protein known as the amyloid protein precursor (APP). In cultured cells, the APP is normally cleaved within the A beta to generate a large secreted derivative and a small membrane-associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire A beta. Our study was designed to determine whether the soluble APP derivatives in human brain end within the A beta as described in cell culture or whether AD brain produces potentially amyloidogenic soluble derivatives that contain the entire A beta. We find that both AD and control brain contain nonamyloidogenic soluble derivatives that end at position 15 of the A beta. We have been unable to detect any soluble derivatives that contain the entire A beta in either the AD or control brain. PMID- 1420207 TI - Psychosocial measures in adolescent health: reflections on the impact of one's publication on subsequent published research. PMID- 1420206 TI - Self-assessment of testicular size. PMID- 1420208 TI - Partner and grandmother contact in black and white teen parent families. AB - Contact of teen mothers with grandmothers and partners was studied as a predictor of maternal and middle childhood developmental outcomes. Mothers were interviewed yearly beginning in 1979 until 1986. Each child was given a developmental assessment in 1986. Black teens lived longer with their parents after the child's birth and white teens married earlier and had more disruptions in their relationships. Grandmother assistance with childcare was positively associated with the mother's ability to pursue her education. The findings suggested, however, that child developmental problems may occur when mothers routinely rely upon grandmother assistance into middle childhood, particularly for white families. In general, a male partner who had regular contact with the mother's child, more stimulation and support in the home environment, and higher educational level of the mother were associated with better child developmental outcomes. PMID- 1420210 TI - Maternal weight status and term birth weight in first and second adolescent pregnancies. AB - The relationship of maternal weight status to birth weight was evaluated retrospectively for the first and second pregnancies of 72 younger (age 12-15 years at first conception) and 80 older (age 16-19 years at first conception) low income adolescents (76% black, 24% white). Mean birth weight increased during the second pregnancies of both groups (277 g and 132 g, respectively). Multiple regression analysis (controlling for potentially confounding variables) indicated a positive relationship between second and third trimester rate of maternal weight gain (kg/week) and birth weight for younger adolescents during their second pregnancy (p = 0.014), and for older adolescents during their first pregnancy (p = 0.047). Mean birth weight increased with each increase in maternal weight-for-height (W/H) category near term from the lowest (< 100% of standard) to the highest (> or = 140% of standard), for both age groups during both pregnancies. Multiple regression analysis indicated that among older adolescents birth weight increased 4.2 +/- 2.0 g (X +/- SE) for each 1% increase in maternal W/H near term in their first pregnancy (p = 0.038) and 7.1 +/- 1.8 g for each 1% increase in maternal W/H near term in their second pregnancy (p = 0.0003). Among younger adolescents these relationships, while in the same direction, were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420211 TI - Beliefs and behavioral intentions regarding human immunodeficiency virus testing among New York City runaways. AB - From 1988 to 1991, 139 runaways aged 11-19 years in the New York City area (n = 70 males, 69 females) were recruited from four shelters. Each runaway participated in a semistructured interview assessing beliefs and behavioral intentions regarding human immunodeficiency virus (HIV) testing. When asked how they would respond to being seropositive for HIV, 29% of runaways reported that they would engage in self-destructive acts and/or harm others (e.g., suicide, unprotected sex), 80% anticipated extreme distress, 47% expected difficulty securing housing and food, and 61% believed that friends were likely to avoid them. When presented with specific alternatives, fewer runaways anticipated self destructive acts. Drug use, rather than sexual behaviors, would lead runaways to get tested for HIV. These results suggest that health-care providers must anticipate emotional distress and potential self-destructive behavior following receipt of documentation of HIV positive serostatus among runaways. Furthermore, prior to testing, youths' access to food, shelter, medical care, and social support must be secured. PMID- 1420209 TI - Young motherhood and infant hospitalization during the first year of life. AB - We studied the relationship of young maternal age with infant hospitalization using data from the National Longitudinal Survey of Youth for 3,130 infants born between 1979 and 1983 to mothers aged 14-25 years. Data on the mothers were first collected in 1979 and yearly thereafter. Data on their children were collected starting in 1982. Logistic regressions of infant hospitalization rates were estimated for first and second and higher births. The odds of infant hospitalization during the first year of life increased with decreasing maternal age, even with adjustment for sociodemographic characteristics, preventive health care practices, and newborn health status, factors hypothesized to explain the maternal age effect. The maternal age relationship with hospitalization differed by birth order; among second and higher births, the odds of hospitalization was increased only for infants of mothers aged 20-22 years. Male infants, infants with a first well-baby visit after the first month of life, with birth weights between 1501 and 2500 g, and with nursery stays longer than 1 week also had increased odds of hospitalization. Ethnicity, grandmother's education, poverty status, mother's school enrollment, and family composition were not related to the odds of hospitalization, nor was smoking during pregnancy when adjustment was made for birth weight and length of nursery stay. PMID- 1420212 TI - An evaluation of a school-based AIDS/HIV education program for high school students. AB - The effect of a 1-hr school-based AIDS/HIV education program on the knowledge and attitudes of high school students was evaluated with a modified version of the Centers for Disease Control Health Risk Survey. One urban and one suburban school each were randomly assigned to an educational intervention (n = 535) or a control group (n = 659). All students received a posttest 2 weeks after the intervention. Knowledge was based on responses to 12 true-false questions (pretest alpha = .76, posttest alpha = 0.81). Principal components analysis was used to develop three attitude scales and risk-taking behavior was assessed by self-report. Data were analyzed with Kruskall-Wallis analysis of variance (ANOVA) and multivariate ANOVA. The groups did not differ in knowledge level at pretest. At posttest the education group had significantly (p < or = 0.006) higher knowledge even after controlling for the effects of previous AIDS education (p < or = 0.019), gender (p < or = 0.007), and Hispanic ethnicity (p < or = 0.048). After the education program, students were less worried about exposure to the AIDS virus, but were more worried (p < or = 0.048) about AIDS acquisition during their adult life. Although single school-based AIDS/HIV education programs may increase knowledge, more extensive education may be needed to change the behavior and attitudes of older high school students. PMID- 1420214 TI - Prepubertal initiation of sexual experiences and older first partner predict promiscuous sexual behavior of delinquent adolescent males--unrecognized child abuse? AB - Sexual experiences of 1580 delinquent adolescent males ages 9-19 years admitted to a juvenile detention center from January 1985 to July 1990 were determined through a structured health history interview. A total of 89.6% admitted to prior sexual activity; 26.8% claimed sexual experience by age 11 years. Only 3.2% reported sexual abuse or incest. Of 334 sexually active adolescents who revealed both age of their first partner and their age of first intercourse, 42% had their first experience with a female 2 or more years older. Males who had their first sexual experience before age 11 years or with a female 2 or more years older, reported significantly larger numbers of sexual partners in their lifetime and during the year preceding their incarceration. Girls with similar first sexual experiences in terms of age of initiation and age difference from partner are considered to be abused. Practitioners who work with children and adolescents need to recognize the possibility of sexual activity among pre-adolescent males and to be aware of its implications. PMID- 1420215 TI - Leisure-time physical activity and aerobic fitness in African-American young adults. AB - This cross-sectional study identified the leisure-time physical activity (LTPA) and aerobic fitness levels of 189 African-American young adult college freshmen. LTPA was measured with the Lipid Research Clinics (LRC), Godin Leisure-Time Exercise, and the College Alumnus physical activity questionnaires. The Physical Activity Index (PAI), an index of walking, stair climbing, and recreational sports participation, was obtained from the College Alumnus questionnaire. Aerobic fitness was measured indirectly with the Cooper 12-Minute Walking/Running Test. More women (82%) than men (53%) were classified as inactive (strenuous exercise or labor < 3 days/week and much less active than peers) or low active (strenuous exercise or labor < 3 days/week and as active or more active than peers) on the LRC Questionnaire. The PAI scores were moderately low in men (1,521 +/- 1,634 kcal.week-1) and very low in women (706 +/- 868 kcal.week-1). The majority of men (71%) and women (82%) were classified as 'very poor' in aerobic fitness levels. Body mass index (BMI), a measure of body fatness, was classified as 'overweight' or 'obese' for 39% of men and 37% of women (BMI = 25.9 +/- 5.7 kg/m2), reflecting inactive LTPA habits. These findings are consistent with studies showing low LTPA in middle-age African-American adults. School and community-level interventions are recommended to increase LTPA and aerobic fitness in adolescent and young adult African-Americans. PMID- 1420216 TI - Use of nonmedical treatment by cystic fibrosis patients. AB - To determine frequency, perceived effectiveness, and cost of religious, physical, and other nonmedical practices, we interviewed all (n = 402; 100% participation) of our cystic fibrosis patients/families [age, 0-45 (median, 18) years]. At least one type of nonmedical therapy was used by/on 264 (66%), two-thirds of which was religious. Most respondents perceived benefit (e.g., group prayer, 95%; religious articles, 81%; chiropractic, 69%). Only 17 (4.2%) invested over $200 lifetime (minimal compared with medical costs). These treatments, apparently used by most patients/families, rarely interfered with medical care. Physician openness and empathy toward patients' beliefs might enhance rapport and facilitate discussion of possible helpful or adverse effects of nonmedical treatment. PMID- 1420217 TI - Physician attitudes toward confidentiality of treatment for adolescents: findings from the Upper Midwest Regional Physicians Survey. AB - The provision of confidential medical services to adolescents is an enduring health policy issue in the United States, and the focus of policy statements by several professional medical organizations. Physician attitudes toward confidential service provision to teenagers were examined in the Upper Midwest Regional Physician Survey, a representative sample of community-based pediatricians and family physicians. Overall, three-quarters of participants favored confidential service provision for youths. Multivariate analysis revealed that the most salient reasons for favoring confidentiality were perception of unique needs among adolescents, year of licensure, high self-assessed competency in addressing sexual concerns of adolescence, adequacy of training in interpersonal and sexual issues, frequency of addressing interpersonal issues, and lower self-assessed adequacy of training in traditional medical problems of youths. Implications for state and federal legislation are discussed. PMID- 1420213 TI - Gender differences in knowledge, intentions, and behaviors concerning pregnancy and sexually transmitted disease prevention among adolescents. AB - Gender differences in knowledge, intentions, and behaviors regarding preventing pregnancies and sexually transmitted diseases were studied. Data for the study were collected from 1,033 students in 13 California high schools. Females in this sample were more likely than males to have discussed sexuality topics with parents, to have engaged in sexual intercourse more frequently, to have experienced a pregnancy scare, to have used oral contraceptives during their last sexual encounter, to perceive that a larger proportion of their peers were engaging in sex and using birth control, to obtain birth control from health facilities, and to report intentions to abstain or use protection in hypothetical situations placing them at risk for unprotected sex. In contrast, males reported that they were more likely to have always used birth control, to have used birth control during their first sexual encounter, and to have used a condom during their last sexual encounter. Furthermore, males were more likely to obtain birth control from a store or a friend. Finally, males knew more about using condoms correctly and their role in preventing sexually transmitted diseases. The efficacy of interventions designed to reduce unintended pregnancy and sexually transmitted diseases among adolescents may be increased by addressing these gender differences. Understanding gender differences may also facilitate an increased role for males in the overall prevention scheme. Further research is clearly needed to increase knowledge about these gender differences. PMID- 1420219 TI - Fatal water intoxication in a young patient with anorexia nervosa. PMID- 1420218 TI - Sexual intercourse, contraception, and risk-taking behavior among unselected French adolescents aged 11-20 years. AB - An epidemiological study was carried out among 4,255 adolescents, aged 11-19 years, randomly selected from secondary schools in a northern urban area of France. The questionnaire concerned sexual activity, contraception, health status, licit and illicit drug consumption, and other risk-taking behavior. A total of 31% of the adolescents had had sexual relations (43% of the boys, 20% of the girls). Sexual activity increased with age. A large majority (70%) of the sexually active adolescents used some form of contraception. The study confirms the relationship between smoking, drinking, illicit drug consumption, and sexual activity, but shows that contraceptive behavior is not related to problem behavior. PMID- 1420220 TI - Oral contraceptives and venous thromboses in adolescents undergoing elective surgery: a case report, and review of the literature. AB - Oral contraceptive (OC) use is a risk factor for the development of deep venous thromboses (DVT) in adolescents, particularly for those patients undergoing surgery. Adolescents have received little attention in the literature on this subject. We describe a 17-year-old female who developed a DVT while receiving OCs at the time of elective surgery. We recommend that adolescent females undergoing elective surgery discontinue OCs at least 1 month before and after the surgery and attendant immobilization. PMID- 1420221 TI - Fiber transformation and fiber replacement in chronically stimulated muscle. AB - Chronic low-frequency stimulation (CLFS) of fast-twitch muscles induces fast-to slow fiber-type transitions that differ in their extent in rat and rabbit. Fast twitch muscle of the normal rat responds to CLFS with sequential transitions in myosin heavy chain (HC) expression in the order HCIIb --> HCIId --> HCIIa. However, in rabbit muscle the changes proceed beyond the state of HCIIa and include, as a final step, the expression of the slow myosin HCI. The time course for the transitions in myosin HC expression at both the messenger ribonucleic acid and protein levels suggests that fiber-type conversions occur asynchronously in a sequential manner. Thus type IIB fibers convert first to type IID fibers; these fibers then transform into type IIA fibers, which in rabbit muscle ultimately change into type I fibers. This sequence and the related changes in myosin isoforms point to different thresholds of the genes encoding the various fast and slow myosin HC isoforms. Although transformation of existing fast fibers into slower fibers is the major process that underlies the stimulation-induced fast-to-slow conversion, fiber replacement may also contribute. In rabbit muscle CLFS may cause metabolic exhaustion and subsequent deterioration in a fraction of the fast-twitch glycolytic fibers. For the most part these are replaced by satellite cell-derived, newly formed slow-twitch fibers. PMID- 1420222 TI - Blood flow to the latissimus dorsi muscle pouch during chronic counterpulsation stimulation. AB - The cyclic contraction of a skeletal muscle ventricle (SMV) stimulated in counterpulsation results in phasic perfusion of the muscle. Perfusion will occur primarily during cardiac systole when the muscle is relaxed. However, the resting preload of the SMV will be systolic arterial pressure, which will impede blood flow to the relaxed muscle. To determine the effect of chronic counterpulsation stimulation on the blood flow to an SMV and identify stimulation regimens that prevent the risk of chronic ischemia, SMVs were created in four mongrel dogs by implementing an implantable mock circulation device. The SMV was stimulated in counterpulsation for 4 weeks after a 2-week vascular delay period and 2 weeks of low-frequency muscle conditioning. During biweekly studies, the muscle was stimulated in four modes against preloads varying from 20 to 120 mm Hg. Resting blood flow decreased significantly at preloads greater than 60 mm Hg. Normalized blood flow increased between 10% and 30% during stimulation; greater increases corresponded to more demanding stimulation modes. The elevated blood flow during stimulation, however, decreased with increasing preload. Stroke work increased with increasing preload until preload exceeded 100 mm Hg. The decreased blood flow and increased stroke work occurring at higher preloads indicate that the supply/demand ratio becomes compromised with increasing preload. A hyperemic response occurred during the resting beats after a stimulated beat, increasing the volume blood flow by as much as 80%. This response occurred regardless of preload or stimulation rate. If the SMV relaxed before the onset of systole, a hyperemic response occurred within the stimulated beat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420223 TI - Significance of the biopsy site of the latissimus dorsi muscle for fiber typing. AB - The use of the latissimus dorsi muscle for cardiomyoplasty requires accurate assessment of the outcome of methods used to convert fast fibers to slow fibers. A knowledge of the normal distribution pattern of slow fibers within the latissimus dorsi is necessary for this endeavor. Fresh latissimus dorsi and teres major muscle tissues from seven pigs, one rabbit, two sheep, one monkey, and four dogs were studied with myosin adenosine triphosphatase staining. Fiber counts were made visually. With the exception of the rabbit, the distribution patterns were similar for all species: (1) intersegmentally--the number of slow fibers decreased steadily from the teres major to the anterior edge of the lateral segment; (2) intrasegmentally--slow fibers were more frequent in the deep layer than the superficial layer; and (3) intrasegmentally--the slow fibers tended to cluster in rosette formations around the neurovascular bundles. These patterns of distribution indicate the need for careful location of biopsies to ensure valid comparison of the amount of slow fibers in tissue before and after treatment. PMID- 1420224 TI - Voltage-dependent performance of skeletal muscle pouches: implications for cardiomyoplasty. AB - Cardiomyoplasty, a new therapy for heart failure, uses autologous skeletal muscle to mechanically assist the heart. The success of dynamic cardiomyoplasty is critically dependent on the contraction strength of the assisting skeletal muscle. Unlike cardiac muscle, skeletal muscle contracts in a graded response to electrical stimulation. However, in current cardiomyoplasty practice, no systematic technique exists to set the stimulating voltage effecting skeletal muscle contraction. The stimulating voltage is simply set to some multiple of the "threshold" voltage. Furthermore, researchers do not consider the role of stimulating voltage when they determine the amount of assistance afforded during cardiomyoplasty. To more accurately assess the value of this heuristic voltage setting technique, we investigated the role of stimulating voltage on the strength of contraction of the latissimus dorsi muscle. Six New Zealand white rabbits had isovolumic hydraulic pouches constructed from the latissimus dorsi muscle. The muscles were wrapped around a compliant balloon in which isovolumic pressure development was measured during tetany-inducing burst (pulse-train) stimulation. The tetanic plateau of the pouch pressure record was used to measure the effects of stimulating voltage on skeletal muscle contraction. Results indicated that (1) increasing stimulating voltage from two to four times the "threshold" voltage increased normalized pouch pressure from 0.38 +/- 0.21 to 0.78 +/- 0.12 (mean +/- SD) (p < 0.05); (2) the threshold-normalized voltage necessary to cause maximal muscle contraction varied widely (5.7 +/- 2.0, mean +/ SD; range, 3.1 to 9.3); and (3) the current achieving maximal pressure development varied from 5.6 to 31.4 mA (19.9 +/- 10.4 mA).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420225 TI - Evaluation of cardiomyoplasty and skeletal muscle ventricle procedures in a clinically realistic animal model. AB - Cardiomyoplasty and skeletal muscle ventricle procedures have shown increasing promise in the treatment of cardiomyopathy with associated chronic congestive heart failure. More than 100 patients have now received such procedures worldwide. The clinical results to date have been mostly anecdotal with subjective improvement but without firm objective data to collaborate the subjective impression. A clinically realistic animal model would have tremendous advantages to help elucidate the mechanisms by which cardiomyoplasty or skeletal muscle ventricles improve the sense of well-being of patients who have congestive heart failure. Several possible animal models exist, including pharmacologically induced congestive heart failure models and postischemic injury cardiomyopathy models. The most intriguing, however, is a spontaneously occurring cardiomyopathy in large dogs. This idiopathic cardiomyopathy that appears mainly in large-breed dogs (Great Danes, Dobermans, and Saint Bernards) has a rapidly progressive course; it has a 6-month mortality rate of 75% and a 12-month mortality rate of 95% to 100%. The most efficacious use of such an experimental model would include the evaluation of cardiomyoplasty and skeletal muscle ventricle procedures in a multidimensional fashion. Experimental endpoints should include mortality, exercise tolerance, systolic and diastolic ventricular function, and arrhythmia occurrence. Sophisticated techniques now exist for the evaluation of systolic and diastolic ventricular function. Such evaluation may well provide additional insight into how such experimental procedures benefit those with congestive heart failure. PMID- 1420226 TI - Skeletal muscle ventricles in circulation long-term: one hundred ninety-one to eight hundred thirty-six days. AB - It has been shown previously that skeletal muscle ventricles fashioned from canine latissimus dorsi muscle can function as effective blood pumps. We describe four dogs that have been reported on before but have now had skeletal muscle ventricles functioning as effective aortic diastolic counterpulsators for 191 to 836 days. One dog remains well with a skeletal muscle ventricle that has been pumping in circulation for 194 days; there has been no evidence of thrombus in the skeletal muscle ventricle cavity or thromboembolism. None of the three dogs that died had evidence of peripheral embolization, although two of those dogs had thrombus within the cavity of the skeletal muscle ventricle. This study proves that skeletal muscle ventricles can function long-term in the circulation and maintain diastolic pressure augmentation beyond 2 years. To the best of our knowledge, the dog whose skeletal muscle ventricle pumped in circulation for 836 days represents the longest living laboratory animal or human with a functioning heart assist device. PMID- 1420227 TI - A new skeletal muscle linear-pull energy convertor as a power source for prosthetic circulatory support devices [corrected]. AB - Previous studies show that stimulated skeletal muscle wrapped around the heart or a blood pumping pouch can provide partial circulatory assistance. However, skeletal muscle is accustomed to pulling in direct tension, and power obtained from using the muscle in wraparound configurations is very inefficient. Therefore we have developed a new skeletal muscle-powered, linear-pull energy convertor for powering a wide range of implanted devices, including circulatory support blood pumps such as counterpulsation devices or complete prosthetic ventricles. This energy convertor system is powered by a skeletal muscle such as the latissimus dorsi, which is stimulated with a pulse generator. With the muscle left intact and in situ as much as possible, its insertion at the humerus is removed and reattached to a small-cylinder hydraulic energy convertor that is firmly attached to the ribs. Mechanical force in direct tension from the muscle is converted to high-pressure, low displacement; hydraulic energy (at approximately 200 psi). The output of this hydraulic energy convertor is connected by a small-diameter tube to a hydraulic actuator to drive the pusher plate of an implantable ventricular assist device located in the thoracic cavity or abdomen or another suitable blood pump. Preliminary in vitro tests from an engineering model of the Thoratec muscle powered ventricular assist device show flow outputs of 5.2 L/min at a mean arterial pressure of 99 mm Hg. The muscle-powered ventricular assist device is a specific application designed to provide completely implantable circulatory support as an alternative to heart transplantation. It will enable patients to experience a quality of life free from batteries and the electrical power conditioning hardware required with electromechanical systems. PMID- 1420228 TI - Successful lung transplantation for posttraumatic adult respiratory distress syndrome after extracorporeal membrane oxygenation support. AB - A severe adult respiratory distress syndrome after bilateral lung contusion was successfully treated by extracorporeal membrane oxygenation and subsequent double lung transplantation in a 19-year-old man. The patient is fully rehabilitated 1 year after transplantation. PMID- 1420230 TI - Comment concerning humoral rejection. PMID- 1420229 TI - When is lung transplantation appropriate? PMID- 1420231 TI - Early infections and bronchiolitis obliterans-organizing pneumonia in single lung transplant recipients. PMID- 1420232 TI - Infections in heart transplant recipients: the experience of the Italian heart transplantation program. Italian Study Group on Infections in Heart Transplantation. AB - Infectious complications are an important cause of morbidity and mortality in heart transplantation. In this report we describe their incidence in the Italian Heart Transplantation Program and their relationship to induction immunosuppressive protocols used. A total of 662 heart transplantations in 651 patients had been performed by March 1, 1990, in 10 Italian centers, with a follow-up of 12,022 patient-months. Actuarial survival at 54 months was 80%. There were 115 deaths, 28 as a result of infection (24%); 30 were perioperative. Mortality from infection was 15% in the first 30 postoperative days and 35% thereafter. During follow-up, 256 life-threatening infectious episodes occurred in 180 patients, for a mean of 1.42 infections/patient. Of these episodes, 28 (10.9%) were lethal. The rate at 54 months, excluding perioperative deaths, was 0.021 episodes/patient-month, with a mean of 0.39 infections/patient in the 651 patient series. At 6 months, 72% of patients were free from infection. This value did not change significantly during subsequent follow-up. Bacterial infections were most frequent (49.2%); fungal (10.5%) and protozoan (5.9%) infections had the worst outcome (lethality 26% and 20%, respectively). A primary cytomegalovirus infection was observed in 23 cases (12 mismatches). Lung involvement (99 episodes) and bacterial sepsis (47 episodes) were most common. Eighty episodes of infection (31.2%) were preceded by a supplementary treatment for rejection with steroid pulses (69%), prednisone boost (20%), or cytolytic therapy (11%). Treatment had preceded the infection by less than 15 days in 55% of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420233 TI - Echocardiographic evaluation of left ventricular wall motion before and after heart transplantation. AB - Forty transplanted hearts were retrospectively investigated before, immediately after, and 15 +/- 12 months after heart transplantation by two-dimensional echocardiography for the presence and course of left ventricular myocardial wall motion abnormalities. Fourteen heart donors who were brain dead because of subarachnoid hemorrhage formed group 1 (mean age, 35 years); 21 heart donors who were brain dead because of head injury formed group 2 (mean age, 29 years), and five heart donors who were brain dead because of head injury with an additional chest trauma formed group 3 (mean age, 28 years). Myocardial wall motion was examined in six different myocardial segments (inferior, septal, anterior, posterior, posterolateral, apical) and was quantitatively assessed by a modified score index system (score index 0 = normal wall motion; score index 1 = diffuse hypokinesia). Overall, 27 of the 40 heart donors showed mild to severe (9 of the 40) wall motion abnormalities, which improved shortly after heart transplantation (score index: 0.36 vs 0.18, p < 0.01), and remained improved 15 months after heart transplantation (score index: 0.15). Among the different study groups, a significant improvement occurred in the myocardial wall motion score index on a short-term and long-term basis in all the groups, except for group 2, regarding the long-term follow-up. This study concluded that brain-dead, potential heart donors often reveal mild-to-severe left ventricular wall motion abnormalities, which are readily detected and semiquantitated by two-dimensional echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420234 TI - Differences in left ventricular filling patterns in heart and heart-lung transplant recipients as assessed by Doppler echocardiography of transmitral flow. AB - The conventional surgical technique of orthotopic heart transplantation involves reconstruction of atria from donor and recipient components. The mechanical function of the atria is thus likely to be altered either by this anatomic disruption or by the autonomic denervation, which also occurs as a result of transplantation. We investigated 18 subjects with Doppler echocardiography of transmitral flow, to assess the contributions of passive and active filling of the left ventricle in six normal subjects, six heart transplant recipients, and six heart-lung transplant recipients. The ratio of passive transmitral flow to active flow was significantly higher in isolated heart transplant recipients than in normal subjects (p < 0.001), suggesting a reduced active, late diastolic component to left ventricular filling. This was not due to denervation, because the ratio in heart-lung recipients was lower than that in normal subjects (p < 0.01). These data suggest that anatomic rather than neural dysfunction is responsible for a major change in transmitral flow characteristics after isolated heart transplantation; whether the resulting change in pattern of left ventricular filling is clinically important deserves further investigation. PMID- 1420235 TI - Global and regional left ventricular function in heart transplant patients: an angiographic follow-up study. AB - We studied the global and regional left ventricular function, its determinants and its modification with time, in orthotopic heart transplant recipients. We reviewed the left ventricular cineangiography performed 1 (50 patients), 2 (33 patients), 3 (18 patients), and 4 (seven patients) years after operation. Regional wall motion was quantitatively evaluated by the area method. All patients had angiographically normal coronary arteries and no evidence of acute rejection at the time of the study. One year after heart transplantation, cardiac index and left ventricular ejection fraction were mildly but significantly lower than normal. Cardiac index was more than 2.5 L/min/m2 in all but one patient, and ejection fraction was more than 50% in all patients. Only previous acute cardiac rejection necessitating therapy and arterial hypertension showed some influence on the left ventricular function. Two years after operation, the left ventricular end-diastolic volume was increased, and left ventricular mass-volume ratio decreased compared with year 1. Three years after operation, an increase of left ventricular end-diastolic pressure and of left ventricular ejection fraction was also evident. Four years after operation, the heart rate was higher, compared with previous years. Even if the changes in the parameters of left ventricular function were significant, they were small in terms of absolute value. Regional hypokinesia was detected 1 year after heart transplantation in eight patients, involving one segment in six patients and two segments in two patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420236 TI - Quantitative analysis of nitroglycerin-induced coronary artery vasodilation in transplanted hearts. AB - Quantitative serial coronary angiograms performed annually over a 3-year period after transplantation in 26 orthotopic heart transplant recipients showed persistently normal nitroglycerin-induced vasodilation. The vasodilator response to nitroglycerin did not predict development of graft arteriopathy; the presence of graft arteriopathy did not prevent a substantial vasodilator response to nitroglycerin. PMID- 1420237 TI - Impact of proximal or midvessel discrete coronary artery stenoses on survival after heart transplantation. AB - To assess survival after the development of transplant coronary artery disease, annual angiography reports from 353 heart transplant recipients were reviewed. Fifty-four patients who survived beyond 1 year and in whom moderate-to-severe proximal or midvessel coronary artery disease developed were identified. Moderate to-severe proximal or midvessel coronary disease was defined for this study as a 40% or more stenosis in 1 or more primary or secondary epicardial arteries. Actuarial survival (Kaplan-Meier) from the time of disease detection in those 54 patients was 67% at 1 year, 44% at 2 years, and 17% at 5 years. Actuarial survival was reduced proportionate to disease severity. Survival for single vessel disease (> or = 40% stenosis) was 64% at 1 year, 36% at 2 years, and 22% at 5 years. Survival was significantly worse with triple-vessel disease (13% at 2 years; p = 0.01) and intermediate for double-vessel disease (41% at 2 years; p = 0.01). Of 19 patients who underwent retransplantation for coronary artery disease, 13 patients (68%) died at a mean of 24 +/- 20 months (range, 1 to 59), and of 15 patients from whom postmortem or angiographic data were available, 11 patients (73%) showed recurrence of significant coronary artery disease in the new graft. Identification of moderate or severe proximal or midvessel coronary disease at angiography predicts an overall mortality rate of more than 50% at 2 years. The poor survival rate in those who underwent retransplantation (around 50% at 4 years) and the high rate of redevelopment of coronary disease suggest that retransplantation should be reserved for selected candidates with angiographically severe disease, if used at all. PMID- 1420238 TI - Total lymphoid irradiation in the treatment of early or recurrent heart rejection. AB - Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered before organ transplantation. Anecdotal reports in clinical transplantation have suggested efficacy of TLI in the treatment of recurrent rejection after heart transplantation. To further assess the safety and efficacy of TLI, 19 patients were entered into a protocol of TLI for the treatment of recurrent or early severe rejection despite conventional therapy. Rejection rate decreased from 1.3 episodes/month before TLI to 0.53 during TLI and 0.07 after TLI (p < 0.0001). Infections increased during TLI (possibly related to recent augmented immunosuppression before TLI), but all infections were successfully treated. One death occurred after TLI from acute allograft rejection. White blood cell (WBC) and platelet counts were depressed during and after (3 months) TLI. Frequent adjustments of dosing interval and, occasionally of the dosage were required to control WBC and platelet counts. Five patients experienced transient WBC of less than 1000/ml. More rejection episodes (and thus greater overall immunosuppression) before TLI and a lower tolerated dose of azathioprine before TLI predicted (by multivariate analysis) a lower WBC during TLI. CONCLUSIONS: (1) TLI is an effective adjunct for the intermediate control of early or recurring acute allograft rejection. (2) Close surveillance of WBC and platelets with appropriate adjustment of TLI dose and interval is necessary during TLI therapy. (3) The long-term benefits, possible late deleterious effects, and potential role of TLI as induction therapy remain to be elucidated. PMID- 1420239 TI - Reevaluation of steroid tapering after steroid pulse therapy for heart rejection. AB - A retrospective analysis was conducted to determine the efficacy and complications resulting from steroid pulse therapy, with or without a steroid taper, in 93 episodes of heart transplant rejection that occurred in 72 patients (58 men, 14 women; mean age, 47.6 years). Each rejection episode was classified according to severity (Texas Heart Institute endomyocardial biopsy scale) and the treatment. Group 1 included 25 episodes of grade 7, 8, 9, or 10 rejection (International Society for Heart Transplantation [ISHT] grade IIIB or IV) that were treated with high-dose methylprednisolone (2.5 to 3.0 gm) and a steroid taper of 1.75 gm over 30 days. Group 2 included 16 episodes of rejection, with the severity of rejection and methylprednisolone pulse therapy being similar to that in group 1, but without a steroid taper. The results of treatment in group 1 were compared with those in group 2. Group 3 included 12 episodes of grade 5, 6, or 7 rejection (ISHT grade IIIA or IIIB) that were treated with moderate-dose methylprednisolone (1.0 to 2.0 gm) and a steroid taper, as described. Group 4 included 40 episodes of rejection, with the severity of rejection and methylprednisolone therapy being similar to that of group 3, but without a steroid taper. The results of treatment in group 3 were compared with those in group 4. No statistically significant differences were found among the groups regarding subsequent episodes of rejection or infection within 3 months of treatment. No statistically significant difference was noted among the groups in the number of rejection episodes requiring additional therapy to control the rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420240 TI - Stability of long-term renal function in heart transplant patients treated with induction therapy and low-dose cyclosporine. AB - Long-term renal function was evaluated in heart transplant recipients who were treated with antilymphocyte globulin induction therapy and low-dose cyclosporine therapy. Although an initial 16% drop in the glomerular filtration rate occurred, long-term follow-up revealed stability of renal function. Four-year patient survival was 77.6%. Use of induction therapy with low-dose cyclosporine may preserve renal function without compromising long-term patient survival. PMID- 1420241 TI - Heart transplantation in patients over 54 years of age with triple-drug therapy immunosuppression. AB - Between April 1, 1986, and December 31, 1989, 206 patients received orthotopic heart transplants with triple-drug therapy immunosuppression (cyclosporine, azathioprine, prednisone). Forty-six patients were aged 55 years or more at the time of transplantation and 160 patients were less than 55 years of age; these two groups were compared. Selection criteria and treatment regimen were the same in both groups. In our experience, although both groups had good postoperative survival, older patients had higher mortality rates early after transplantation, particularly from rejection and infection. Patients over 55 years of age had similar nonfatal rejection rates and were no more likely to have infectious episodes than younger patients. As demand for heart transplantation increases and waiting lists lengthen, the age of potential recipients should be an important factor in deciding how to allocate scarce donated organs, although age should not be exclusive. PMID- 1420242 TI - Neurologic complications of heart transplantation in children. AB - Neurologic complications can add significant morbidity to otherwise successful orthotopic heart transplantations in children. Complications have been reported to occur in up to 50% of children undergoing heart transplantation. The purpose of this study was to identify the prevalence and outcome of neurologic complications of heart transplantation in children. We reviewed all children who received orthotopic heart transplantation at Texas Children's Hospital from November 1984 to November 1990. Twenty-two patients (ages, 3 weeks to 17 years; mean, 8.5 years) underwent heart transplantation using cardiopulmonary bypass with moderate hypothermia. For analysis, we compared results during the first 3 years of our experience, 1984 through 1987 (group 1), to 1987 through 1990 (group 2). Survival was 45% (5 of 11 patients) for group 1 and 73% (8 of 11 patients) for group 2. A neurologic complication was defined as a change in the neurologic examination and/or status. Neurologic complications included seizures (6 of 22 patients), strokes (3 of 22 patients), unresponsiveness (3 of 22 patients), and change in mental status (2 of 22 patients). Early (within 2 weeks after operation) neurologic complications occurred in 45% (10 of 22 patients), were persistent (sequelae lasting more than 4 months) in 27% (6 of 22 patients), and resulted in death in 9% (2 of 22 patients). Late (after 2 weeks after operation) neurologic complications occurred in 23% (5 of 22 patients), were persistent in 9% (2 of 22 patients), and have occurred in only two survivors. Neurologic factors were not responsible for the cause of death in group 2. No neurologic complications (early or late) were seen in 1 of 11 patients in group 1 as compared with 7 of 11 patients in group 2 (p < 0.015). Serious neurologic morbidity decreased between the two groups after preoperative cyclosporine was avoided and postoperative hypertension was controlled. All survivors are functioning at age-appropriate levels. Although neurologic complications may be frequent, long-term neurologic disability in survivors is rare. PMID- 1420243 TI - Long-term results in diabetic patients undergoing heart transplantation. AB - We conducted a retrospective study of 305 nondiabetic patients and 37 diabetic patients who underwent heart transplantation from July 1982 to May 1990. Actuarial survival was similar for both groups of patients at 1 year (76.4% versus 81.3%) and at 2 years (69.6% versus 73.0%). Because we were interested in long-term results, we further analyzed only those patients surviving more than 1 year after transplantation (214 nondiabetic patients and 29 diabetic patients). Mean follow-up for the nondiabetic patients was 31.8 +/- 16.2 months and for the diabetic patients, 32.9 +/- 4.1 months. The respective mean age in each group was 50.4 +/- 10.3 years and 51.6 +/- 9.1 years. No difference was observed between the nondiabetic patients and diabetic patients regarding the rejection rate per patient-month (0.040 +/- 0.041 versus 0.045 +/- 0.051 episodes per patient month), the infection rate per patient-month (0.056 +/- 0.081 versus 0.081 +/- 0.102 episodes per patient-month), or renal function as evidenced by mean creatinine levels at 1, 2, and 3 years. Twelve patients were insulin-dependent before transplantation; and 1 year after transplantation, they required an insulin dose 2.12 times greater than the dose before operation. Coronary artery disease developed in 32.8% of the nondiabetic patients, compared with 31.0% of the diabetic patients by the fourth year of follow-up. Despite the need for increased insulin doses, the diabetic patients had similar long-term survival to that of the nondiabetic patients, without an increased risk of rejection, infection, renal dysfunction, or coronary artery disease. Our experience supports the feasibility of heart transplantation in selected diabetic recipients. PMID- 1420244 TI - Cyclosporine A and prednisone-associated osteoporosis in heart transplant recipients. AB - Immunosuppressive therapy with cyclosporine A or prednisone produces bone loss in some animal models. Although we have clinically observed osteoporotic fractures in our heart recipients, the effects of cyclosporine and prednisone on bone density in transplant populations has not been fully elucidated. This study was undertaken to examine indexes of mineral metabolism and bone mineral density (BMD) in heart transplant recipients referred for evaluation of possible bone disease. Twenty of 93 patients who underwent heart transplantation at our institution were evaluated for osteoporosis. Sixteen of these patients (eight men; eight women) were included in this cross-sectional study (two patients were excluded because of hyperparathyroidism, and two patients were excluded because severe fractures prevented BMD from being measured). The mean age of the heart transplant recipients was 52.4 +/- 2.2 years, and the study was conducted a mean of 33.4 +/- 4.6 (men) and 19.0 +/- 7.0 (women) months after heart transplantation. Forty-four percent of these heart transplant recipients were seen clinically with fractures. Biochemical tests of skeletal homeostasis and BMD measurements with dual energy x-ray absorptiometry were performed. In male and female patients, the indexes of mineral metabolism showed (mean +/- sem) osteocalcin levels of 9.60 +/- 2.3 micrograms/L and 9.46 +/- 1.9 micrograms/L (normal: men, 6.39 +/- 0.69 micrograms/L; women, 5.87 +/- 0.71 micrograms/L) and intact parathyroid hormone levels of 48.8 +/- 10.3 ng/L and 63.4 +/- 10.7 ng/L (normal: men, 26.8 +/- 3.3 ng/L; women, 30.7 +/- 2.1 ng/L), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420245 TI - Prevention of loss of vertebral bone density in heart transplant patients. AB - Seventy-six patients (63 men, 13 women) have been followed up by vertebral bone density (VBD) studies from 3 to 36 months. VBD was measured by single-energy computerized tomographic scan. Before transplantation, VBD was found to be lower than in age-matched controls (less than 40 years of age [group 1], 96% of controls: 40 through 49 years of age [group 2], 77%; 50 to 60 years of age [group 3], 87%; more than 60 years of age [group 4], 76%). After transplantation, despite oral calcium supplements, VBD fell further in all but two patients (97%), which was almost certainly related to maintenance steroid and cyclosporine therapy, and was most marked in the older groups (group 2, 67% compared with age matched controls at 6 months; group 3, 60%; group 4, 50%). Intensive therapy with synthetic salmon calcitonin (in 29 of 76 patients [38%]), testosterone (in 33 of 63 men [52%]), or estrogen (in 12 of 13 women [92%]) limited, but did not totally prevent, further loss in VBD; in patients who had shown an approximate 45% loss of VBD from pretransplantation levels, further loss was reduced to between 4% and 10%. Five patients increased bone density after calcitonin therapy. Despite significantly reduced VBD in several older patients, minor vertebral bone compression developed in only one patient. We recommend that all patients undergoing heart transplantation, particularly those over the age of 50 years, should be followed by VBD studies, and therapy should be administered to prevent VBD loss. PMID- 1420246 TI - Cardiac xenografting in the pig-to-rhesus monkey model: manipulation of antiendothelial antibody prolongs survival. AB - Transplantation of immediately vascularized grafts across species barriers in which preformed cytotoxic antibodies exist, otherwise known as discordant combinations, has uniformly resulted in hyperacute rejection. We studied how well plasma exchange and perfusion through organs removes preformed immunoglobulin M cytotoxic antibodies and prolongs survival of a porcine heart heterotopically transplanted into a rhesus monkey. With the use of plasma exchange or absorption of antibodies by porcine kidney perfusion with or without immunosuppression, graft survival was prolonged, although antibody-mediated rejection ultimately occurred. In one case in which plasma exchange, kidney perfusion, and immunosuppression were combined, a functioning pig heart survived in a rhesus monkey for 8 days without evidence of rejection. The animal was killed on day 8 according to protocol because of a wound dehiscence. With this animal we were able to demonstrate that circulating antibodies against graft endothelium had bound to the graft endothelium without inducing rejection, a process referred to as accommodation. In this case, despite the presence of antiendothelial antibodies, complement did not appear to be activated, and fibrin thrombi did not form. Although we have achieved this rejection-free survival only in one animal, this case suggests that it may be possible to maintain xenotransplants in discordant species without rejection if preformed antibodies are appropriately lowered or altered during the initial period of graft implantation. PMID- 1420247 TI - The effects of interferon-alpha/beta in a model of rat heart transplantation. AB - Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone. PMID- 1420248 TI - TPEN, a transition metal chelator, improves myocardial protection during prolonged ischemia. AB - In view of the hypothesis that free radicals induced damage during ischemia and reperfusion is mediated by transition metals, we investigated the effect of the potent metal chelator TPEN (N,N,N'N'-tetrakis(-)[2-pyridylmethyl] ethylenediamine) on cardiac function after prolonged myocardial ischemia. Isolated working rat hearts were subjected to 12 hours of cold ischemic arrest followed by reperfusion for 1 hour. The study was carried out on five groups (nine hearts in each): (1) St. Thomas' Hospital cardioplegic solution; (2) St. Thomas' Hospital cardioplegic solution with 7.5 mumol/L TPEN; (3) protection conditions as in group 2, but with TPEN administration during preischemic and reperfusion periods; (4) University of Wisconsin solution; and (5) the same conditions as in group 4 with TPEN administration during the preischemic and reperfusion periods. Significant enhancement of hemodynamic recovery was observed in the presence of TPEN throughout the experiment. The recovery of cardiac output was 24% +/- 4% in group 3, as compared to 12% +/- 4% in group 1 (p < 0.01). The postischemic left ventricular pressure recovery was 57% +/- 4% in group 3, as compared to 18% +/- 7% in group 1 (p < 0.005). The hearts in group 5 recovered, reaching 29% +/- 2% of the preischemic cardiac output and at 65% +/- 2% of the left ventricular pressure recovery (p < 0.05 versus group 3). Lactate dehydrogenase was released throughout the reperfusion. TPEN addition to groups 2 and 3 did not significantly reduce lactate dehydrogenase release; however, TPEN in University of Wisconsin solution and throughout the experiment significantly decreased lactate dehydrogenase release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420249 TI - Donor heart preservation survey. AB - A questionnaire requesting information on donor heart preservation technique and outcomes during the first 6 months of 1990 was circulated to heart transplantation centers worldwide. Seventy-nine usable replies representing 1371 clinical transplant operations were received. Twenty-seven percent of the respondents reported using some form of donor pretreatment. Most (90%) used single flush cardioplegic induction with the use of eight different types of cardioplegic solutions, only 5% of which were oxygenated. Six different types of storage media were used, and the coolant was melting ice in 66% of the centers. Storage temperatures between 0 degrees C and 7 degrees C were reported, with 78% of the respondents using 4 degrees C storage. Fifty-five percent of the centers used some form of reperfusion modification. No statistically significant associations were noted between outcome and technique, apart from the use of storage medium in which the use of cardioplegic solution conferred a 2.5 times increase in deaths compared with cold saline. The results of this questionnaire provide evidence for the diversity of techniques currently used for donor heart preservation, reflecting the lack of any one optimal method. PMID- 1420250 TI - Histologic changes in donor bronchi may explain the reduced mucosal blood flow seen during acute lung allograft rejection. AB - We assessed the histologic changes in donor and recipient bronchi from 15 dogs that had received a lung transplant and related these changes to the severity of acute rejection seen in the parenchyma of these same lungs. Minimal rejection was associated with no abnormal change in either the donor or the recipient bronchi. In mild lung rejection, mononuclear cell cuffings were seen around bronchial arteries in donor bronchial adventitia, although few mononuclear cell infiltrates were seen in the submucosa. Moderate lung rejection was associated with more prominent mononuclear cell cuffings in the donor bronchial adventitia and mucosal infiltrates of mononuclear cells in the membranous portion. In cases of severe lung rejection, the mononuclear cell infiltrates were also apparent in the cartilaginous portion of the donor bronchial mucosa. Moreover, submucosal edema and detachment of bronchial epithelium were seen. These histologic changes were not observed in the recipient bronchi during acute rejection, nor were they seen in the donor and the recipient bronchi during lung infection without rejection. They might, therefore, reflect acute rejection in the donor bronchus. These results might provide the histologic support for our previous observation of decreased bronchial mucosal blood flow measured by the laser Doppler flowmeter in relation with the extent of acute lung rejection. PMID- 1420251 TI - Different patterns of cell volume regulation in hyposmotic media between attached and suspended HeLa cells. AB - Both attached and suspended HeLa cells swelled in a medium of a hypotonic osmolality of 235 mosmol/kg H2O. When the osmolality was further decreased to 166 mosmol/kg H2O, attached cells instantly swelled and then rapidly lost water and K+, followed by slow gains of them. Suspended cells instantly swelled and then K+ loss and regulatory volume decrease (RVD) occurred. Neither 0.1 mM ouabain nor 10 mM TEA changed the water loss of attached cells, whereas ouabain inhibited RVD of suspended cells. Quinine (1 mM) inhibited water losses from both cells and comparison of the losses implies stronger activation of K+ channel in attached cells than in suspended cells. Omission of medium Ca2+ or addition of 10 mM BaCl2 inhibited RVD in part. These results suggest that hyposmotic stress induces net water loss from attached cells, associated with K+ release through the Ca(2+) dependent K+ channel. Suspended cells osmotically swell, followed by RVD with K+ and Na+ releases through the K+ channel and Na(+)-pump, respectively. The different patterns of volume changes may relate to the difference of activity or time of activation of the K+ channel between both cells. PMID- 1420252 TI - Permeability of lipid bilayers to amino acids and phosphate. AB - Permeability coefficients for amino acid classes, including neutral, polar, hydrophobic, and charged species, were measured and compared with values for other ionic solutes such as phosphate. The rates of efflux of glycine, lysine, phenylalanine, serine and tryptophan were determined after they were passively entrapped in large unilamellar vesicles (LUVs) composed of egg phosphatidylcholine (EPC) or dimyristoylphosphatidylcholine (DMPC). The following permeability coefficients were obtained for: glycine, 5.7 x 10(-12) cm s-1 (EPC), 2.0 x 10(-11) cm s-1 (DMPC); serine, 5.5 x 10(-12) cm s-1 (EPC), 1.6 x 10(-11) cm s-1 (DMPC); lysine, 5.1 x 10(-12) cm s-1 (EPC), 1.9 x 10(-11) cm s-1 (DMPC); tryptophan, 4.1 x 10(-10) cm s-1 (EPC); and phenylalanine, 2.5 x 10(-10) cm s-1 (EPC). Decreasing lipid chain length increased permeability slightly, while variations in pH had only minor effects on the permeability coefficients of the amino acids tested. Phosphate permeability was in the range of 10(-12)-10(-13) cm s-1 depending on the pH of the medium. The values for the polar and charged amino acids were surprisingly similar to those previously measured for monovalent cations such as sodium and potassium, which are in the range of 10(-12)-10(-13) cm s-1, depending on conditions and the lipid species used. This observation suggests that the permeation rates for the neutral, polar and charged amino acids are controlled by bilayer fluctuations and transient defects, rather than partition coefficients and Born energy barriers. The results are relevant to the permeation of certain peptides into lipid bilayers during protein translocation and membrane biogenesis. PMID- 1420254 TI - Exchange efflux of [3H]palmitate from human red cell ghosts to bovine serum albumin in buffer. Effects of medium volume and concentration of bovine serum albumin. AB - [3H]Palmitate, PA, exchange efflux kinetics is recorded from human erythrocyte ghosts to buffer with bovine serum albumin, BSA, at 0 degrees C. The effects have been investigated of three medium/ghost volume ratios: 36, 80 and 500, of six BSA concentrations, [BSA]: 0.01, 0.02, 0.05, 0.2, 1 and 2% (1.5, 3.0, 7.5, 30, 150 and 300 microM) and of various v, molar ratios of palmitate to BSA, between 0.15 and 0.94. Data are analyzed in terms of a virtually closed three-compartment model. In theory, the tracer efflux is biexponential and the rate coefficients differ at least 20 fold [1]. The efflux rate at 2% BSA is monoexponential beyond our resolution time of about 1 s, but nearly biexponential at or below 0.2% BSA with a well-defined smallest-rate coefficient beta. beta depends strongly on [BSA] but is remarkably v independent. The medium/ghost volume ratio has no effect on beta when [BSA] > or = 0.2%, although beta measured at 2% BSA is almost 2-fold higher than at 0.2%. This suggests the presence of an unstirred layer, USL. According to our model, the observations are understood quantitatively on basis of our previously published dissociation rate constants of the PA-BSA complex, as well as PA equilibrium bindings to ghost membranes (Bojesen, I.N. and Bojesen, E. (1991) Biochim. Biophys. Acta 1069, 297-307). Essentially, beta is theoretically a function of two terms, one comprising the membrane transport parameters and the other the medium-dependent variables. Most important is the clearance with respect to monomer concentration adjacent to the membrane. The clearance is calculated on basis of quasi-stationary diffusion in USL. The data are compatible with a planar USL of 6 microns depth and with the same area as a ghost but not with a spherical USL. PMID- 1420253 TI - Localization of the binding domain of the inhibitory ligand forskolin in the glucose transporter GLUT-4 by photolabeling, proteolytic cleavage and a site specific antiserum. AB - The binding domain of forskolin in the adipocyte/muscle-type glucose transporter (GLUT-4) was localized with the aid of the photoreactive derivative, [125I]IAPS forskolin (3-[125I]iodo-4-azidophenethylamido-7-O-succinyldeacetyl-forskolin). Plasma membranes from insulin-treated rat adipocytes containing predominantly the GLUT-4 isoform were irradiated with UV light in the presence of [125I]IAPS forskolin. The covalently labeled glucose transporters were isolated by immunoprecipitation with specific antiserum and partially digested with trypsin and elastase. The fragments were separated by gel electrophoresis, transferred on to nitrocellulose membranes, and identified by direct autoradiography and by immunoassay with antiserum against a peptide sequence corresponding to the C terminus of GLUT-4. Digestion with a high-purity grade trypsin generated two photolabeled fragments with apparent molecular weights of 21 and 16 kDa. Since the antiserum detected two fragments with identical electrophoretic mobility, both labeled fragments appeared to contain the intact C-terminus of GLUT-4. In contrast, digestion with elastase generated only one photolabeled fragment with intact C-terminus at 21 kDa, and a smaller unlabeled fragment with intact C terminus at 15 kDa. A less pure trypsin preparation generated two labeled (21 and 17 kDa) and one unlabeled (15 kDa) fragment with intact C-terminus. These data suggest that the site of covalent binding of IAPS-forskolin in the GLUT-4 is located within a region of 1-6 kDa defined by the difference between the unlabeled C-terminal fragment (15 kDa) and the labeled fragments (21, 17 and 16 kDa). Based on a tentative allocation of the fragments to the sequence of the GLUT-4, it is suggested that the covalent binding site of IAPS-forskolin is located between the membrane spanning helices 7-9, possibly in the proximity of helix 9. PMID- 1420255 TI - Alteration of the passive electrical properties of lymphocyte membranes induced by GM1 and GM3 glycolipids. AB - The electrical conductivity of normal human lymphocyte suspensions has been measured in the frequency range from 10 kHz to 100 MHz, where a well-pronounced conductivity dispersion occurs, caused by the surface polarization at the interface between the cell membrane and the extracellular solution. We have investigated the alteration of the passive electrical properties of the cytoplasmatic cell membrane induced by two different gangliosides (GM1 and GM3) inserted, at various concentrations, into the outer leaflet of membrane double layer. The alterations observed in the dielectric parameters (the membrane conductivity and the membrane permittivity) derived on the basis of a 'double shell' model, result in an overall increase of the ion permeation across the membrane and an enhanced polarizability of its hydrophilic region for both gangliosides investigated. The relevance of these alterations is discussed. PMID- 1420256 TI - A new diffusion chamber system for the determination of drug permeability coefficients across the human intestinal epithelium that are independent of the unstirred water layer. AB - A new method for determining permeability coefficients, that are independent of the unstirred water layer (UWL), has been developed. The method was used to determine the cellular permeability coefficient of the rapidly absorbed drug testosterone in monolayers of the human intestinal epithelial cell line, Caco-2. Using a new diffusion cell with an effective stirring system based on a gas lift, the cellular permeability coefficient for testosterone was (1.98 +/- 0.13).10(-4) cm/s which is 3.5-times higher than the permeability coefficient obtained in the unstirred system. The thickness of the UWL obtained with the well stirred diffusion cell was 52 +/- 4 microns. This value is much lower than those previously reported in various well stirred in vitro models. The calculated cellular permeability of testosterone was 13-23-times lower than that for an UWL of the same thickness as the epithelial cell (17-30 microns). We conclude that the permeability of the epithelial monolayer must be included in calculations of the thickness of the UWL. PMID- 1420257 TI - Influence of staphylococcal delta-toxin on the phosphatidylcholine headgroup as observed using 2H-NMR. AB - The interaction of the 8-toxin peptide isolated from Staphylococcus aureus with the headgroup region of lipid bilayer membranes composed of 1-palmitoyl-2-oleoyl sn-glycero-3-phosphocholine (POPC) was investigated using deuterium (2H) and phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy. At relatively low peptide/lipid ratios (P/L < 0.10), all 2H- and 31P-NMR spectral lineshapes at 25 degrees C were indicative of a single population of liquid-crystalline lipids in a bilayer arrangement. At these P/L ratios, delta-toxin had only marginal effects on the size of the quadrupole splitting measured from POPC labelled at either the alpha-methylene (POPC-alpha-d2) or the beta-methylene segment (POPC-beta-d2) of the choline headgroup and, similarly small effects on the magnitude of the chemical shift anisotropy (CSA) of the 31P-NMR spectrum. With increasing amounts of delta-toxin (0.10 < P/L < 0.15) the size of the 2H quadrupole splitting from POPC-alpha-d2, as well as the magnitude of the 31P-CSA, decreased progressively and rapidly. The quadrupole splitting from POPC-beta-d2, however, remained relatively unaffected. At yet higher levels of delta-toxin (P/L > 0.15), all 2H- and 31P-NMR spectra indicated the presence of multiple lipid populations experiencing varying degrees of increased conformational disordering. The spectral lineshapes of these apparently nonbilayer spectral components reverted to bilayer-type lineshapes upon lowering the measuring temperature to 5 degrees C. At the utmost highest level of delta-toxin measured here (P/L = 0.20), all 2H- and 31P-NMR spectra consisted of a single, broad, apparently nonbilayer-type component, indicative of hindered but virtual isotropic motional averaging of the POPC headgroups. In this case no reversion to bilayer-type spectra could be obtained by decreasing the temperature. We could obtain no evidence that the conformation of the choline headgroup of POPC was responding to any specific influence of delta-toxin on bilayer surface electrostatics. PMID- 1420258 TI - Expression of GLUT-2 cDNA in human B lymphocytes: analysis of glucose transport using flow cytometry. AB - The molecular characterization of transport proteins is often limited by transient functional expression or the need for a simple method to select functional cDNA clones. We used a mammalian expression system to obtain long-term expression of GLUT-2, an isoform of glucose permease. Rat GLUT-2 cDNA was ligated into an EBV vector (pLPP) and transfected into B lymphocytes which lack GLUT-2. Northern and Western analyses confirmed expression of GLUT-2 protein in membranes of transfected cells. Two functional assays using flow cytometry were developed to distinguish GLUT-2 transfectants from control/pLPP transfectants. Uptake of NBD-glucosamine, a fluorescent analogue of glucose, was increased in GLUT-2 transfectants. In addition, when exposed to hypertonic glucose medium, GLUT-2 transfectants and control/pLPP transfectants exhibited a difference in forward angle light scatter (FALS), an index of cell volume, indicating a difference in glucose permeability. Independent measurements of glucose uptake (isotopic) and cell volume (video microscopy) confirmed the flow cytometry observations. This expression system used in combination with flow cytometry is useful for studying the functional properties of glucose and other solute transporters. PMID- 1420259 TI - Effect of cationic cholesterol derivatives on gene transfer and protein kinase C activity. AB - Four different cationic derivatives of cholesterol were synthesized which contain either a tertiary or a quaternary amino head group, with and without a succinyl spacer-arm. Their ability to inhibit protein kinase C (PKC) activity was measured in a detergent mixed micellar solution. Derivatives containing a quaternary amino head group were effective inhibitors (Ki approx. 12 and 59 microM) of PKC and derivatives containing a tertiary amino head group were approx. 4-20-fold less inhibitory. Liposomes containing an equimolar mixture of dioleoylphosphatidylethanolamine (DOPE) and a cationic cholesterol derivative were tested for the DNA-mediated transfection activity in mouse L929 cells. Highest activity was found with the derivative with low PKC inhibitory activity and with a succinyl spacer-arm. The transfection activity of this tertiary amine derivative, N,N-dimethylethylenediaminyl succinyl cholesterol was dependent on DOPE as a helper lipid; liposomes containing dioleoylphosphatidylcholine and this derivative had little activity. The transfection protocol of this new cationic liposome reagent was optimized with respect to the ratio of liposome/DNA, dose of the complex and time of incubation with cells. Several adherent cell lines could be efficiently transfected with this liposome reagent without any apparent cytotoxicity. However, the transfection activity was strongly inhibited by the presence of serum components. PMID- 1420260 TI - Retinal and retinol promote membrane fusion. AB - Disk membranes from the bovine retinal rod outer segments (ROS) were found to fuse with vesicles made of lipids extracted from unbleached ROS disk membranes, using a lipid mixing assay for membrane fusion (relief of self-quenching of R18, octadecylrhodamine B chloride). If the retinal chromophore of rhodopsin was reductively linked to opsin before lipid extraction, the vesicles made of the extracted lipids were not suitable targets for fusion of the disk membranes. The addition of retinal and retinol to these vesicles restored their ability to fuse. Therefore, the presence of all-trans retinal was implicated in promoting membrane fusion in this system. To test this possibility, the ability of retinal and retinol to influence the phase behavior and the fusion capability of large unilamellar vesicles (LUV) of N-methyl dioleoylphosphatidylethanolamine (N-methyl DOPE) was examined. Both retinal and retinol stimulated the fusion of vesicles of N-methyl-DOPE (contents mixing with ANTS, 1-aminonaphthalene-3,6,8-trisulfonic acid; DPX, p-xylylene bis(pyridinium bromide)). Both compounds reduced the onset temperature for isotropic resonances in the 31P-NMR spectra of N-methyl-DOPE dispersions and the onset temperature, TH, for formation of hexagonal II phase. These results were consistent with previous studies in which the onset temperature for the 31P-NMR isotropic resonances were correlated with stimulation of membrane fusion. These data suggested that both retinal and retinol may stimulate membrane fusion by destabilizing the bilayers of membranes. PMID- 1420261 TI - The mechanism of the solute-induced chain interdigitation in phosphatidylcholine vesicles and characterization of the isothermal phase transitions by means of dynamic light scattering. AB - A new method is introduced for the detection of chain interdigitation in phospholipid bilayers. The same method is used to measure the hydrocarbon tilt in the dipalmitoylphosphatidylcholine membranes as a function of the bulk concentration of the interdigitation-inducing solutes, such as ethanol. The hydrocarbon tilt in the phosphatidylcholine bilayers is demonstrated to be limited to angles below approx. 51 degrees. The need for higher tilt values leads to bilayer interdigitation. Solute-induced chain interdigitation is shown to be a cooperative process provoked by the excessively large lateral repulsion in the interfacial region and the concomitant excessive chain tilt. Ethanol-induced phosphatidylcholine interdigitation, for example, proceeds via interdigitated domains formation and finally gives rise to the bilayers with fully intercalated chains tilted by at least 30 degrees (and sometimes as much as 50 degrees) with respect to the membrane normal. PMID- 1420262 TI - Cocaine induces intracellular free Mg deficits, ischemia and stroke as observed by in-vivo 31P-NMR of the brain. AB - 31P-NMR spectroscopic studies were performed in vivo on brains of rats administered cocaine. Cocaine.HCl (1-5 mg/kg) administered systemically to lightly anesthetized rats resulted in significant and progressive deficits in whole brain intracellular free Mg ([Mg2+]i). Intracellular pH (pHi) also fell in a progressive manner but only after a significant fall in brain [Mg2+]i was noted. Both [Mg2+]i and pHi returned to normal in most rats. Brains of rats that exhibited stroke-like events, however, demonstrated continued intracellular acidosis associated with progressive loss of phosphocreatine and elevation of Pi up until death. These observations are consistent with the tenet that injection of cocaine can result in severe cerebral vasospasm, ischemia and rupture of cerebral blood vessels as a consequence of depletion of brain [Mg2+]i. PMID- 1420263 TI - Comparative analysis of latrotoxin channels of different conductance in planar lipid bilayers. Evidence for cluster organization. AB - It has been established that channels induced by Latrodectus tredicimguttatus alpha-toxin (LT) in lipid bilayers have a cluster organisation. So far as: (i) the LT-channels had practically identical sizes of its water pores (r = 9.4 +/- 0.6 A) independently on the lipid composition of planar bilayer lipid membrane (BLM) although their conductances might differ from each other more than 10 times (100 mM KCl (pH 7.5)). (ii) affinity of permeable ions to channels had a small variation with distinct group of BLM, although LT-channels conductances varied from 112 +/- 8 pS till 1110 +/- 40 pS for phosphatidylcholine-BLM and from 75 +/- 6 pS till 170 +/- 14 pS for phosphatidylserine-BLM. (iii) Ca/K selectivity was greater in negatively charged membranes but did not also depend on the channel amplitude for the same BLM. Cation-anionic selectivity was identical for all studied channels. PMID- 1420264 TI - Sequence analysis of the catalytic subunit of H(+)-ATPase from porcine renal brush-border membranes. AB - The catalytic subunit of the H(+)-ATPase from brush-border membranes of porcine renal proximal tubules was labeled with the hydrophobic SH-group reagent 10-N (bromoacetyl)amino-1-decyl-beta-glucopyranoside (BADG) which irreversibly inhibits proton pump activity in the absence but not in the presence of ATP. The labeled protein was purified and digested with proteinases. After isolation and sequencing of proteolytic peptides two BADG-labeled cysteines were identified. The amino acid sequences of the obtained proteolytic peptides were homologous to the catalytic subunit of V-ATPases. From mRNA of porcine kidney cortex a catalytic H(+)-ATPase subunit was cloned. 181 of the 183 amino acids which overlap in the sequence derived from the cDNA and the proteolytic peptides were identical, and the two deviations are due to single base exchanges. A comparison of the amino acid sequence derived from the cloned cDNA with sequences of catalytic H(+)-ATPase subunits communicated by other laboratories revealed 98%, 96% and 94% identity with sequences from bovine adrenal medulla, from bovine kidney medulla and from clathrin-coated vesicles of bovine brain. Between 64% and 69% identity was obtained with sequences from fungi and plants. The data show that the catalytic subunit of V-ATPases is highly conserved during evolution. They indicate organ and species specificity in mammalians. PMID- 1420265 TI - Carrier-mediated transport system for choline and its related quaternary ammonium compounds on rat intestinal brush-border membrane. AB - The characteristics of the intestinal transport system for choline were investigated using isolated brush-border membrane vesicles from rat small intestine. In spite of the diminutive lipid solubility, the uptake of choline by membrane vesicles reflected smooth permeation into intravesicular space rather than the binding to the membrane surface. Physiological conditions, present in the intact intestine, such as an inward-directed Na+ or H+ gradient and inside negative membrane potentials, didn't directly involve in choline transport across the brush-border membrane. Moreover, an outward-directed H+ gradient had no significant effect on the time course of choline transport. However, in the absence of a driving-force, the initial uptake of choline exhibited a saturable manner. A kinetic analysis of the initial uptake rate gave an apparent Km of 159 microM. Furthermore, unlabeled choline caused both cis-inhibition and trans stimulation for labeled choline transport, suggesting the existence of a carrier mediated transport system for choline, classified as so-called 'facilitated diffusion'. Since tetramethylammonium, acetylcholine, and N1-methylnicotinamide caused both cis-inhibition and trans-stimulation, they appear to be accepted as the substrate of choline carrier. On the other hand, quaternary ammonium compounds (QACs) such as those which possessed hydrophobic parts in their molecules exhibited only cis-inhibition. They also inhibited Na(+)-dependent D glucose transport, indicating that they influenced various carrier-mediated transport systems non-specifically due to interaction with the membrane. These findings strongly suggest that the choline transport system on the brush-border membrane of rat intestine recognizes only small molecular QACs as its substrate. PMID- 1420266 TI - Monolayer study of plastoquinones, alpha-tocopherol quinone, their hydroquinone forms and their interaction with monogalactosyldiacylglycerol. Charge-transfer complexes in a mixed monolayer. AB - The surface pressure-area isotherms of pure plastoquinone-9 (PQ-9), plastoquinone 3 (PQ-3), alpha-tocopherol quinone (alpha-TQ), their reduced (hydroquinone) forms and mixtures of these molecules with monogalactosyldiacylglycerol (MGDG) have been studied by a monolayer technique. The collapse pressures of all hydroquinones (QH2) were higher than those of the corresponding quinones (Q), the difference being highest between PQ-9 and PQH2-9. The limiting molecular areas of hydroquinones were higher than those of the corresponding quinones except for alpha-TQH2. All Q-QH2 mixtures showed miscibility throughout the whole range of the components' ratios. There was no deviation from the additivity rule observed for any of the Q-QH2 mixture, as well as for the mixtures of MGDG with PQ-3, PQH2 9, alpha-TQ and alpha-TQH2. On the other hand, PQ-9/MGDG and PQH2-3/MGDG mixtures showed positive and negative deviations, respectively. All the isotherms of Q MGDG and QH2-MGDG mixtures showed a kink point above the collapse pressure of the Q or QH2 examined, indicating that with the increase in surface pressure, Q or QH2 were gradually squeezed out from the monolayer. The percent content of Q and QH2 in the monolayer as a function of surface pressure was also calculated. The hydroquinones were more difficult to remove from monolayers than the corresponding quinones, and among the investigated quinones, PQ-9 was most easily and alpha-TQ most difficulty squeezed out. The surface pressure-area isotherms of the three-component mixtures of PQ-9/PQH2-9/MGDG showed a shift to lower molecular areas in comparison with the corresponding two-component mixtures, especially at higher surface pressures. This indicates that the presence of PQ-9 lowered the PQH2-9 content in the monolayer, especially at higher pressures, which was explained by charge-transfer complex formation upon interaction of PQ-9 with PQH2-9. The comparison of surface potential-area isotherms of PQ-9/PQH2 9/MGDG mixtures with those of the corresponding binary mixtures also suggest charge-transfer interaction between PQ-9 and PQH2-9. The orientation and localization of the investigated quinones and quinols in the thylakoid membrane and significance of charge-transfer interactions in functioning of PQ-9 has been discussed. PMID- 1420267 TI - A volume-sensitive chloride conductance revealed in cultured human keratinocytes by 36Cl- efflux and whole-cell patch clamp recording. AB - The Cl- transport mechanism responsible for the stimulation of 36Cl- efflux after exposure to hypotonic medium (210 mosmol/kg) was investigated in human keratinocytes. The involvement of the anion exchanger and of the Cl-/cation cotransporters was ruled out by the finding that replacement of extracellular Cl- by the poorly permeant anion gluconate, and the addition of bumetanide and furosemide, inhibitors of the Na+/K+/Cl- and K+/Cl- cotransporters, respectively, failed to significantly reduce the activation of Cl- efflux by hypotonic medium. 'Whole cell' configuration of the patch clamp technique directly revealed the presence of a macroscopic Cl- current, which was evoked by incubation with hypotonic medium and was reversed by elevation of the extracellular osmolality. Volume-sensitive current showed outward rectification of the current-voltage relationship and time-dependent inactivation at depolarizing voltages. This current was Cl- selective, because the zero-current reversal potential approached the Cl- equilibrium potential, when extracellular Cl- was replaced by gluconate. 0.1 mM 1,9-dideoxyforskolin significantly reduced either 36Cl- efflux and the Cl- current, suggesting that the Cl- efflux and the macroscopic current activated after exposure to hypotonic medium are mediated by the same pathway. Electronic cell sizing showed that in keratinocytes hypotonic swelling was not followed by a significant regulatory volume decrease response. PMID- 1420268 TI - Atrial natriuretic peptide degradation by CPA47 cells: evidence for a divalent cation-independent cell-surface proteolytic activity. AB - Atrial natriuretic peptide (ANP) is rapidly cleared and degraded in vivo. Nonguanylate-cyclase receptors (C-ANPR) and a metalloproteinase, neutral endopeptidase (EC 3.4.24.11) (NEP 24.11), are thought to be responsible for its metabolism. We investigated the mechanisms of ANP degradation by an endothelial derived cell line, CPA47. CPA47 cells degraded 88% of 125I-ANP after 1 h at 37 degrees C as determined by HPLC. Medium preconditioned by these cells degraded 41% of the 125I-ANP, and this activity was inhibited by a divalent cation chelator, EDTA. Furthermore, a cell-surface proteolytic activity degraded 125I ANP in the presence of EDTA when receptor-mediated endocytosis was inhibited either by low temperature (4 degrees C) or by hyperosmolarity at 37 degrees C. The metalloproteinase, NEP 24.11, is unlikely to be the cell-surface peptidase because 125I-ANP is degraded by CPA47 cells at 4 degrees C in the presence of 5 mM EDTA. These data indicate that CPA47 cells can degrade ANP by a novel divalent cation-independent cell-surface proteolytic activity. PMID- 1420269 TI - Phase behaviour and molecular species composition of oat root plasma membrane lipids. Influence of induced dehydration tolerance. AB - Tolerance to dehydration induced by repeated water-deficit stress is well correlated to changes in the lipid composition of oat root cell plasma membranes. The molecular species of the two dominant phospholipids phosphatidylcholine and phosphatidylethanolamine were determined. The four major species were 16:0/18:2, 16:0/18:3, 18:2/18:2 and 18:2/18:3. In contrast to the large changes in plasma membrane lipid composition in other respects, induced tolerance resulted in very weak alterations concerning the phospholipid molecular species pattern. Only minor alterations, appearing as a decrease in the 18:3-containing lipids, occurred. Total lipids of microsomes and isolated plasma membranes of root cells were analysed by X-ray crystallography at different degrees of hydration. The lipid phase behaviour at different degrees of hydration was further confirmed by polarization microscopy. In the presence of excess water all membrane lipids adopted a reversed micellar configuration. The plasma membrane lipids from root cells with induced dehydration tolerance formed upon dehydration two coexisting lamellar structures. The importance of the phase behaviour at different degrees of hydration for the membrane properties and the relation to membrane composition is discussed. PMID- 1420270 TI - A new system for bilayer lipid membrane capacitance measurements: method, apparatus and applications. AB - A new method and a new apparatus for capacitance measurements on bilayer lipid membranes are described. The membrane is charged and discharged with a constant current during the measurement. The charge-discharge cycle duration, which is proportional to the membrane capacitance, is measured. The measured time period is converted into a binary number by digital systems and then this number is either further converted into a constant capacity-proportional voltage or read out by the computer. The apparatus makes it possible to measure the capacitances of voltage-polarized membranes. Application of the apparatus to capacitance measurements of bilayer lipid membranes during their potential on the capacitance is presented. The capacitances of membranes stimulated by rectangular voltage pulses and of those stimulated by a linearly varying potential were reported. PMID- 1420271 TI - Single Ca(2+)-activated K+ channels in human erythrocytes: Ca2+ dependence of opening frequency but not of open lifetimes. AB - Using the patch-clamp technique single-channel properties of Ca(2+)-activated K+ (CaK) channels were investigated in inside-out membrane patches of human erythrocytes. In a physiological K+ gradient (5 mM K+ externally: 150 mM K+ internally) the single CaK channel conductance is 15 pS in the membrane potential range of -40 to +40 mV. The channel open probability, opening frequency and open and closed time distributions are voltage-independent. The open probability and the opening frequency of the CaK channel depend on [Ca2+]i and increase between 0.5 and 60 microM Ca2+ from approx. 10% to 90% of the maximum value obtained at 115 microM. The relation between open probability and [Ca2+]i can be described by a sigmoid concentration-effect curve with an EC50 of 4.7 microM and a slope factor of 1. Independent of [Ca2+]i open time distributions yield two time constants of 5.3 and 22 ms. The relative amplitudes of the fast and slow components of the open time histogram as well as the maximum open probability and the maximum opening frequency of CaK channels vary considerably. In addition, CaK channels in multiple channel patches are highly interdependent. It is concluded that the Ca(2+)-dependence of CaK channels in human erythrocytes is due to the modulation of opening frequency by internal Ca2+. The results are consistent with a classical receptor-agonist model in which ligand interaction kinetics are much faster than channel gating. PMID- 1420272 TI - Properties and the primary structure of a new halorhodopsin from halobacterial strain mex. AB - A new halorhodopsin-like pigment from the new halobacterial strain mex (Otomo, J., Tomoika, H. and Sasabe, H. (1992) J. Gen. Microbiol. 138, 1027-1037) was partially purified, and its amino acid sequence from helices A to G was determined using PCR technique. Two arginine residues in the A-B interhelix loop segment, a series of six amino acid residues (EMPAGH) in the B-C interhelix segment and most of the residues near the Schiff base of the retinal were found to be conserved in three halorhodopsins (halobium, pharaonis and mex). This result strongly suggests that these residues are essential for anion pumping function in halorhodopsin. The light-induced ion-pump measurements have shown that the selectivity of anion transport between chloride and nitrate in mex halorhodopsin is lower than that of halobium halorhodopsin, but higher than that of pharaonis halorhodopsin. The number of amino acid residues in the B-C interhelix loop segments is different in each halorhodopsin, and it correlates with their anion (chloride and nitrate) selectivity. These results suggest that the length of the B-C segment affects the selectivity of anion transport in halorhodopsin. PMID- 1420273 TI - Distinct metal ion binding sites on Ca(2+)-activated K+ channels in inside-out patches of human erythrocytes. AB - Effects of Cd2+, Co2+, Pb2+, Fe2+ and Mg2+ (1-100 microM) on single-channel properties of the intermediate conductance Ca(2+)-activated K+ (CaK) channels were investigated in inside-out patches of human erythrocytes in a physiological K+ gradient. Cd2+, Co2+ and Pb2+, but not Fe2+ and Mg2+, were able to induce CaK channel openings. The potency of the metals to open CaK channels in human erythrocytes follows the sequence Pb2+, Cd2+ > Ca2+ > or = Co2+ >> Mg2+, Fe2+. At higher concentrations Pb2+, Cd2+ and Co2+ block the CaK channel by reducing the opening frequency and the single-channel current amplitude. The potency of the metals to reduce CaK channel opening frequency follows the sequence Pb2+ > Cd2+, Co2+ >> Ca2+, which differs from the potency sequence Cd2+ > Pb2+, Co2+ >> Ca2+ to reduce the unitary single-channel current amplitude. Fe2+ reduced the channel opening frequency and enhanced the two open times of CaK channels activated by Ca2+, whereas up to 100 microM Mg2+ had no effect on any of the measured single channel parameters. It is concluded that the activation of CaK channels of human erythrocytes by various metal ions occurs through an interaction with the same regulatory site at which Ca2+ activates these channels. The different potency orders for the activating and blocking effects suggest the presence of at least one activation and two blocking sites. A modulatory binding site for Fe2+ exists as well. In addition, the CaK channels in human erythrocytes are distinct from other subtypes of Ca(2+)-activated K+ channels in their sensitivity to the metal ions. PMID- 1420274 TI - The structural and functional organization of the baseplate distal part of T4 bacteriophage. AB - The structural organization of the baseplate distal part of bacteriophage T4 has been studied. The investigations resulted in revealing the functional role of gene products '11' and '12' in the course of baseplate reorganization and DNA injection. A new model of 'arrangement' of gp12 in the intact particle is suggested. A functional interrelationship between long fibers of the phage and the protein complex of baseplate distal part has been established. PMID- 1420275 TI - Chemical assessment of phospholipid and phosphoenergetic metabolites in regenerating rat liver measured by in vivo and in vitro 31P-NMR. AB - For the assessment of 31P-NMR spectroscopic data, phospholipid precursors (phosphorylethanolamine (PE) and phosphocholine) and catabolites (glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC)), as well as adenosine phosphates were chemically determined in regenerating rat liver. The data were compared with those obtained by in vivo and in vitro 31P-NMR spectroscopies. Chemical assay revealed a significant increase of PE and a decrease of GPE, GPC and ATP in hepatectomy group compared to sham operation group. The values obtained by in vitro NMR were in good agreements with those of chemical assay, but significant differences between the two groups were observed only in PE and inorganic phosphate (Pi). Noticeable increase in PME was not detected by in vivo 31P-NMR spectroscopy, although the increase of PE was about 2.5-times that of the control and its constitution ratio to the whole phosphomonoester (PME) was less than 15%. On the other hand, in vivo NMR showed a large phosphodiester (PDE) peak occupying approx. 40% of the total phosphorus signal, while the contribution of its constituents, GPE and GPC was about 5% found by both chemical assay and in vitro NMR. The PDE peak in in vivo NMR seemed to reflect the membrane phospholipid itself rather than its catabolites. A slight decrease of phosphoenergetic level in regenerating rat-liver was commonly suggested by all three analytical methods. PMID- 1420276 TI - Long-lived fluorescence lifetime from tyrosine in a peptide derived from S-100b. AB - It was shown in an earlier report (Turner et al., 1989, Biochem. Cell Biol. 67; 179-186) that the anomalous steady-state fluorescence emission spectra observed for the protein S-100b in aqueous solution at pH 7.5 contains a long-lived fluorescence decay component. In this study, a peptide consisting of residues 11 to 27 of the beta-subunit, was investigated. 11Ile-Asp-Val-Phe-His15-Gln-Tyr-Ser Gly-Arg20-Glu-Gly- Asp-Lys-His25-Lys-Leu27 Fluorescence lifetimes were measured at the emission maximum and in the red edge of the spectrum. At wavelengths greater than 320 nm, the data was best fit with three exponentials. The third exponential gave lifetimes of 13.1 ns and 15.9 ns when the peptide was dissolved in the solvents propane-2-ol and propane-1,2-diol, respectively (lambda EX = 275 nm, lambda EM = 350 nm). These fluorescence lifetimes are similar to that observed for a decay component of native S-100b in the red edge of the emission, suggesting that the 1 degrees and 2 degrees features of a heptadecapeptide from S 100b protein has enough structural information when dissolved in solvents of intermediate polarity provide appropriate conditions for long-lived fluorescence from a tyrosine/tyrosinate species to occur. PMID- 1420277 TI - Purification, characterization and partial amino acid sequences of a xylanase produced by Penicillium chrysogenum. AB - An extracellular xylanase (1,4-beta-D-xylan xylanohydrolase, EC 3.2.1.8, endo 1,4 beta-xylanase) was found to be the major protein in the culture filtrate of Penicillium chrysogenum when grown on 1% xylan. In contrast to other microorganism no xylanase multiplicity was found in P. chrysogenum under the conditions used. This enzyme was purified to homogeneity by high performance anion-exchange and size-exclusion chromatography. It had an M(r) of 35,000 as estimated by SDS-PAGE and was shown to be active as a monomer. No glycosylation of the protein could be detected neither by a sensitive glycostain nor by enzymatic deglycosylation studies. The enzyme hydrolyzed oat spelt and birchwood xylan randomly, yielding xylose and xylobiose as major end products. It had no cellulase, CMCase, beta-xylosidase or arabinogalactanase activity but acted on p nitrophenylcellobioside. The pH and temperature optima for its activity were pH 6.0 and 40 degrees C, respectively. Eight peptides obtained after endoproteinase LysC digestion of xylanase have been sequenced, six of them showed considerable amino acid similarity to glucanases and high M(r)/acidic xylanases from different bacteria, yeasts and fungi. PMID- 1420278 TI - Unequivocal evidence in support of the nonenzymatic redox coupling between glutathione/glutathione disulfide and ascorbic acid/dehydroascorbic acid. AB - Experiments were performed to evaluate the nonenzymatic reaction between glutathione (GSH) and dehydroascorbic acid (DHA). Though both ascorbic acid and glutathione disulfide (GSSG) are formed from this reaction, previous work has focused almost exclusively on measurements of ascorbic acid. In contrast, there is very little information about the formation of GSSG under the same conditions as those used to produce ascorbic acid. The emphasis on ascorbic acid stems from the fact that a spectrophotometric technique is available for its measurement, whereas 1H-NMR or an amino acid analyzer has been used to measure GSSG. The present experiments use a simple, rapid method for accurately and precisely measuring the concentrations of GSSG in a solution. The spectrophotometric (340 nm) procedure uses NADPH and glutathione reductase; analysis time is very short, many replicate samples can be tested and as little as 0.05-0.1 mM GSSG can be detected. Using this method, it is shown that there is an equimolar production of GSSG and ascorbic acid from GSH and DHA and that the decrease in GSH is stoichiometrically related to the increase in the concentration of GSSG. The present findings provide additional insight into the interaction between the GSH/GSSG redox couple and the ascorbic acid/DHA redox couple. PMID- 1420279 TI - Characterisation of chondroitin/dermatan sulphate proteoglycans synthesised by rat mammary myoepithelial and fibroblastic cell lines. AB - Chondroitin sulphate proteoglycans were isolated from the culture medium of rat mammary gland fibroblast (Rama 27) and myoepithelial (Rama 401) cell lines which had been labelled with [35S]sulphate. Chromatography on Sepharose CL-4B indicated that the Rama 401 proteoglycan was larger than the Rama 27 proteoglycan (Kav values 0.47 and 0.56, respectively). Treatment of the proteoglycans with alkaline NaBH4 yielded chondroitin sulphate chains with average M(r) values of 37,000 (Rama 401) and 21,000 (Rama 27). Structural analysis of the glycosaminoglycan chains indicated that both were co-polymers of chondroitin and dermatan sulphate although there were differences in the amounts and distribution of the disaccharide repeating units. The M(r) values of the core proteins, determined by immunoblotting, were about 43,000 and 46,000 (Rama 27) and 44,500 (Rama 401). Using an antibody to chondroitin sulphate proteoglycan in immunofluorescence experiments, the proteoglycan was demonstrated on the surface of both cell lines. Rama 27 cells additionally possessed an extensive fibrous extracellular matrix which also stained with the antibody. Staining of sections of lactating mammary gland suggested that the proteoglycan was present in the basement membrane as well as the stromal connective tissue. The presence of chondroitin sulphate proteoglycan in the basement membrane was confirmed by ultrastructural immunolocalisation. PMID- 1420281 TI - Purification and characterization of zeta-crystallin/quinone reductase from guinea pig liver. AB - zeta-Crystallin, a major lens protein of certain mammalian species, has recently been characterized as a novel and active NADPH:quinone oxidoreductase. Here we report the purification of this protein from guinea pig liver by utilizing sequentially: ammonium sulphate precipitation, Blue Sepharose affinity, cation exchange and hydrophobic chromatography steps. This four-step isolation procedure yielded 118-fold purification and a specific activity of 6 U/mg protein when assayed in the presence of 9,10-phenanthrenequinone. Kinetic, immunological and physical properties of this protein have been found to be identical with those of guinea pig lens zeta-crystallin. Western blot analysis using antibodies raised against zeta-crystallin peptides demonstrated the presence of substantial amounts of this protein in human liver homogenates. PMID- 1420280 TI - Immunochemical characterization and toxicological significance of P-450HFLb purified from human fetal livers. AB - Immunochemical properties of P-450HFLb purified from human fetal livers were investigated. P-450HFLb cross-reacted with antibodies to rat P-4501A1 but not with antibodies to CYP2A6, CYP2C9, CYP3A7 (P-450HFLa) and rat CYP2B1. In addition, P-450HFLb also cross-reacted with both monospecific antibodies to rat CYP1A1 and CYP1A2. However, P-450HFLb was shown to be an immunochemically distinct form of cytochrome P-450 from P-450PA (human CYP1A2). Immunoblot analysis of human fetal livers with the antibodies to P-450HFLb showed that P 450HFLb was expressed in all fetal livers studied although there appeared to be individual differences in the amounts of P-450HFLb expressed in fetal livers. The formation of mutagens from IQ (but not from AFB1) in fetal liver homogenates was inhibited by the antibodies to P-450HFLb in a dose dependent manner. These results suggest that P-450HFLb may be a form of human cytochrome P-450 classified into CYP1 gene family, and that the cytochrome P-450 is, in part, responsible for the mutagenic activation of IQ in human fetal livers as well as CYP3A7 (P 450HFLa). PMID- 1420282 TI - The role of serum and serum components in the merocyanine 540-sensitized photoinactivation of K562 leukemia cells. AB - Serum is known to inhibit the merocyanine 540 (MC540)-sensitized photoinactivation of cells and enveloped viruses in a concentration-dependent manner. In diagnostic applications of MC540, a moderate amount of serum or serum albumin is frequently added to the staining solution because it enhances the contrast between intensely staining cells (e.g., electrically excitable cells or leukemia cells) and cells with a lower affinity for the dye (e.g., nonexcitable cells, red cells, normal leukocytes). In this communication we report on a quantitative analysis of the interactions of MC540 with serum and serum components. Human serum inhibited the MC540-sensitized photoinactivation of K562 leukemia cells most effectively, followed in order of decreasing potency by calf, newborn calf, horse, and fetal bovine serum. The photoprotective capacity of these five sera was directly proportional to their albumin content. Gel filtration experiments and differential spectroscopy showed that MC540 bound to serum albumin and lipoproteins. Both delipidated and lipidated albumin were capable of binding MC540. However, lipidated albumin had a considerably higher binding capacity and affinity for dye molecules. PMID- 1420283 TI - Measurement of the formation of betaine aldehyde and betaine in rat liver mitochondria by a high pressure liquid chromatography-radioenzymatic assay. AB - A new assay procedure for measurement of rat liver mitochondrial choline dehydrogenase was developed. Oxidation of [methyl-14C]choline to [methyl 14C]betaine aldehyde and [methyl-14C]betaine was measured after isolating these compounds using HPLC. We observed that NAD+ was required for conversion of betaine aldehyde to betaine in rat liver mitochondria. In the absence of this cofactor, oxidation of choline led to the accumulation of betaine aldehyde. The apparent Km of the mitochondrial choline dehydrogenase for choline was 0.14-0.27 mM, which is significantly lower than previously reported. A partially purified preparation of choline dehydrogenase catalyzed betaine aldehyde formation only in the presence of exogenous electron acceptors (e.g., phenazine methosulfate). This preparation failed to catalyze the formation of betaine even in the presence of NAD+, indicating that betaine aldehyde dehydrogenase may be a separate enzyme from choline dehydrogenase. PMID- 1420284 TI - Mammalian lipoxygenases: molecular structures and functions. PMID- 1420285 TI - Hypertriglyceridemia is exacerbated by slow lipolysis of triacylglycerol-rich lipoproteins in fed but not fasted streptozotocin diabetic rats. AB - Hydrolysis by endothelial lipases of triacylglycerol-rich lipoproteins of diabetic origin were compared to lipoproteins of non-diabetic origin. The plasma lipoprotein fraction of density < 1.006 g/ml, including chylomicrons and VLDL, were incubated in vitro with post-heparin plasma (PHP) lipases. The lipoproteins of diabetic origin were hydrolysed at a significantly slower rate than lipoproteins from normal rats by the lipoprotein lipase component of PHP. However, if rats were fasted for 16 h prior to lipoprotein recovery, no differences in rates of VLDL hydrolysis were observed. Slower hydrolysis of lipoproteins of diabetic origin reflected a decrease in the apolipoprotein CII/CIII ratio and other changes in the apolipoprotein profile. To assess whether diabetic rats were less able to clear triacylglycerol independent of changes in the nature of the lipoproteins, we monitored the clearance of chylomicron-like lipid emulsions in hepatectomized rats. In vivo, emulsion triacylglycerol hydrolysis was not slowed due to diabetes. However, control and diabetic rats, which had been fasted for 16 h, cleared triacylglycerol at about twice the rate of fed rats. Triacylglycerol secretion rates in diabetic and control rats were similar, whether fed or fasted. We conclude that in streptozocin diabetic rats, hypertriglyceridemia was not due to overproduction of chylomicron- or VLDL triacylglycerol, nor to decreased endothelial lipase activities. Rather, in fed diabetic rats, the triacylglycerol-rich lipoproteins are poorer substrates for lipoprotein lipase. This may lead to slower formation of remnants which would exacerbate slow remnant removal. VLDL of diabetic origin were hydrolysed as efficiently as VLDL from control donors, suggesting that in the fed state the lipolytic defect may be specific for chylomicrons. PMID- 1420287 TI - Modified apolipoprotein pattern after irradiation of human high-density lipoproteins by ultraviolet B. AB - The ultraviolet B-induced destruction of tryptophan residues and lipid peroxidation of high-density lipoproteins is accompanied by the immediate and marked structural modification of the apolipoproteins, as revealed by SDS polyacrylamide gel electrophoresis and immunoblot with specific monoclonal antibodies. Formation of several polymers of apolipoprotein A-I, apolipoprotein A II or both apolipoproteins occurred, although apolipoprotein A-II did not contain any Trp residue. These results suggest that initial photochemical damage can be transferred via intramacromolecular processes to other sites within the same apolipoprotein and by intermacromolecular reactions from apolipoprotein A-I to other apolipoproteins. In both cases, lipid peroxidation enhances the propagation of the initial photochemical damage. The physiological significance of this work is discussed with respect to the low-light doses required for the alterations of the high-density lipoproteins. PMID- 1420286 TI - Oxidized HDL are much less cytotoxic to lymphoblastoid cells than oxidized LDL. AB - The possible effect of oxidized HDL was investigated on lymphoblastoid cells, in comparison to the cytotoxic effect of oxidized LDL. Oxidation of HDL was promoted by UV-C irradiation, or by copper ion (5 microM) or the combination of the two treatments. HDL extensively treated by UV-C for 20 h did not exhibit any cytotoxic effect on cultured lymphoblastoid cells even at a concentration of 500 micrograms apolipoprotein A-I/ml. In contrast to UV-treated (2 h) LDL, which were highly cytotoxic (already at a concentration of 100 micrograms apolipoprotein B/ml), HDL treated by copper or copper + UV were oxidized, as shown by TBARS formation and PUFA content decrease, but were slightly cytotoxic. PMID- 1420288 TI - Opposite regulation of hepatic lipase and lecithin: cholesterol acyltransferase by glucocorticoids in rats. AB - Rats were treated with hydrocortisone, dexamethasone or triamcinolone for 4 days. The effect of treatment on hepatic lipase and lecithin:cholesterol acyltransferase (LCAT) mRNA levels and catalytic activities was determined. Hepatic lipase mRNA was not affected by hydrocortisone, but was decreased after dexamethasone (-28%) and triamcinolone (-54%). Hepatic lipase activity followed the same pattern, it was not affected by hydrocortisone and lowered by dexamethasone (-38%) and triamcinolone (-70%). The LCAT mRNA level in the liver was also not affected by hydrocortisone, but increased upon treatment with dexamethasone (+22%) and triamcinolone (+72%). Plasma LCAT, determined with an excess exogenous substrate (designated LCAT-II), tended to decrease after hydrocortisone treatment (-11%) and was higher after dexamethasone (+21%) and triamcinolone (+22%). The plasma cholesterol esterification rate (designated LCAT I), determined by incubation of the plasma at 37 degrees C, followed the same pattern. The activity ratio of hepatic lipase/LCAT-II decreased from 1 in the controls to 0.51 after dexamethasone and 0.25 in the triamcinolone-treated animals. The plasma HDL cholesterol concentration in the different groups changed oppositely to the hepatic lipase/LCAT activity ratio. It is concluded that HDL cholesterol is raised by synthetic glucocorticoids due, among other factors, to a lowered hepatic lipase and an increased plasma LCAT activity. The influence of glucocorticoids on these enzymes is, at least partly, explained by the effects on the hepatic mRNA contents. PMID- 1420290 TI - Effects of 2-tetradecylglycidic acid on rat platelet energy metabolism and aggregation. AB - We investigated the role of energy supplied by long-chain fatty acid oxidation in rat platelet function. Inhibition of the mitochondrial uptake of long-chain fatty acids was achieved by treating rats with 2-tetradecylglycidic acid (TDGA), a potent inhibitor of the overt form of carnitine palmitoyltransferase (CPT-I). The maximum aggregation rate (MAR), CPT-I activity, lactate production, oxygen consumption and adenine nucleotide content of isolated rat platelets were then studied in vitro. 4 h after the in vivo administration of TDGA, the CPT-I activity in saponin-permeabilized platelets was nearly completely inhibited along with a significant reduction in the MAR induced by ADP, thrombin and ionophore A23187. The ATP level, adenylate energy charge (ATP + 1/2 ADP)/(ATP + ADP + AMP) and ATP/ADP ratio in the platelet cytoplasmic pool were also reduced. Platelets from TDGA-treated rats showed lower oxygen consumption rates in both the basal respiratory and oxygen burst states. These results indicate that mitochondrial long-chain fatty acid oxidation coupled to oxidative phosphorylation is an important energy source in rat platelets and is probably involved in the maintenance of platelet function. Enhanced in vitro lactate production in platelets from TDGA-treated rats may have resulted from a compensatory increase in glycolysis which only partly compensated for impaired long-chain fatty acid oxidation. PMID- 1420289 TI - Effect of interleukin-1 alpha on lipoprotein lipids in cynomolgus monkeys: comparison to tumor necrosis factor. AB - Acute inflammation is associated with changes in lipoprotein metabolism. Cytokines are thought to mediate the metabolic effects of the inflammatory process. This study was undertaken to compare the effects of interleukin-1 alpha (IL-1 alpha) to tumor necrosis factor (TNF) on lipoprotein metabolism in non human primates. Recombinant human IL-1 alpha (100 micrograms/kg), TNF alpha (20 micrograms/kg) and lipopolysaccharide (20 micrograms/kg) were injected into cynomolgus monkeys. Lipoprotein concentrations, plasma activities of post-heparin lipase (PHLA) and lecithin:cholesterol acyltransferase (LCAT) were measured prior to and 24 and 48 h after, injection. All three injections caused afebrile response in the animals. Interleukin-1 alpha had no effect on plasma lipoprotein concentrations, composition of lipoproteins or enzyme activity. In contrast, injection of TNF caused significant changes in lipoprotein concentrations. There was a 38% increase in plasma triacylglycerol and 30% decrease in plasma cholesterol at 48 h after injection. Concentrations of apolipoproteins A-I and B were decreased 20% and 44%, respectively, at 48 h. Compositional analyses of lipoprotein particles after TNF injection showed that both the LDL and HDL particles had decreased content of cholesterol ester and increased triacylglycerol after injection, and plasma activities of PHLA and LCAT were decreased. These changes were qualitatively similar to those seen after LPS injection. These data suggest that, unlike TNF, IL-1 alpha is not an important mediator of the inflammatory process on lipoprotein metabolism in cynomolgus monkeys. PMID- 1420291 TI - Lipid composition, phospholipid profile and fatty acid of rat caecal mucosa. AB - In this study, we examined the lipid composition of rat caecal mucosa, including the fatty acid composition of major phospholipid classes. Phospholipids accounted for 90% of the total lipid, with cholesterol, triacylglycerols, diacylglycerols, fatty acids and cholesterol ester making up the remainder. Therefore, a phospholipid to neutral lipid ration of 9:1 was found. Phosphatidylethanolamine was the predominant phospholipid, with phosphatidylcholine as the second most abundant phospholipid. Cardiolipin, phosphatidylserine, phosphatidylinositol and lysophosphatidylcholine were present in lesser amounts. Sphingomyelin and lysophosphatidylethanolamine were only detected in trace amounts. The major fatty acids present in both the lipid and all phospholipid fractions were palmitate, stearate, oleate, linoleate and arachidonate. Other fatty acids of chain length greater than C20 were only detected in phospholipid fraction and accounted for < 5% of the total fatty acids in this fraction. However, 11.10% of 22:6 (n-3) and 7.17% of 24:0 were detected in phosphatidylserine and lysophosphatidylcholine, respectively. The results are discussed in terms of their possible physiological significance. PMID- 1420293 TI - Inhibition by serum components of oxidation and collagen-binding of low-density lipoprotein. AB - Low-density lipoprotein (LDL) is oxidized by cellular and noncellular mechanisms, both leading to an increased binding to collagen. We have investigated the effect of serum on lipid peroxidation, apoprotein oxidation and the binding of oxidized apoprotein to collagen. During noncellular oxidation, lipoprotein-deficient serum strongly inhibited all three processes. The serum fraction of M(r) > 100,000 was equally inhibitory; this effect was not due to alpha 1 or gamma globulins, alpha 2 macroglobulins, haptoglobins or ceruloplasmin. The serum fraction of M(r) 30,000-100,000 stimulated the binding of oxidized apoprotein but the albumin in this fraction inhibited lipid peroxidation and apoprotein oxidation. Serum ultrafiltrate (M(r) < 1000) inhibited lipid and protein oxidation, and binding; the inhibitory effect was abolished by deionization which removed histidine. The effects of lipoprotein-deficient serum and its fractions on cellular oxidation were similar but weaker than those on noncellular oxidation, HDL inhibited noncellular oxidation as well as binding of oxidized apoprotein. VLDL also inhibited oxidation; this could not be accounted for by its content of apo B. If present in vivo, these inhibitory effects would completely suppress both cellular and noncellular oxidation of LDL and its subsequent binding to collagen. PMID- 1420292 TI - Hypoxia increases stimulus-induced PAF production and release from human umbilical vein endothelial cells. AB - Hypoxia alters endothelial cell function and metabolism. Since PAF is synthesized by endothelial cells and capable of modulating endothelial cell responses, we investigated the effect of hypoxia on synthesis and release of PAF from endothelial cells. We found: (1) Approx. 90% of the radylPAF derivative in stimulated endothelial cells is acylPAF. (2) Acute hypoxic (15 min-1 h) priming increased ionophore- and thrombin-induced radylPAF accumulation. (3) Long-term hypoxic exposure increased radylPAF accumulation at 24 and 48 h in the presence of ionophore. (4) Bioactive PAF was released into media and hypoxia and ionophore synergistically increased PAF release. (5) Hypoxia and ionophore stimulation increased phospholipase A2 activity and decreased acetylhydrolase activity in endothelial cells. We conclude that hypoxia and ionophore increase PAF synthesis and release from endothelial cells. PMID- 1420294 TI - Isolation and properties of gamma-tocopherol methyltransferase in Euglena gracilis. AB - Gamma-Tocopherol methyltransferase (EC2.1.1.-), which catalyzes the conversion of gamma-tocopherol into alpha-tocopherol, was present in a cell homogenate of Euglena gracilis. The enzyme was loosely bonded to the outer membrane of chloroplasts and solubilized from chloroplast membranes by a detergent, followed by partial purification in a three-step procedure. The methyltransferase showed a pH optimum of 7.5 and a temperature optimum of 35 degrees C and had an M(r) of 150,000. The activity was about 1.4-fold higher with gamma-tocopherol than with beta-tocopherol as substrate. The enzyme was specific for S-adenosylmethionine as a methyl donor, with a Km value of 50 microM. The addition of homogentisate, L tyrosine and L-phenylalanine into a suspension of Euglena cells increased the relative pool sizes of alpha- and gamma-tocopherol, but not those of beta- and delta-tocopherol. The contents of alpha- and gamma-tocopherol in a chloroplast fraction of Euglena were always higher than those of any other fraction after any period of incubation with homogentisate. Based on the results of the present experiments, we propose a biosynthetic pathway of alpha-tocopherol in Euglena gracilis. PMID- 1420295 TI - Black lipid membranes of tetraether lipids from Thermoplasma acidophilum. AB - Black lipid membranes were formed of tetraether lipids from Thermoplasma acidophilum and compared to the bilayer forming lipids diphytanoylphosphatidylcholine and diphythanylglucosylglycerol. Bilayer-forming lipids varied in thickness of black lipid membranes due to the organic solvent used. Measurements of the specific membrane capacitance (Cm = 0.744 microF/cm2) showed that the membrane-spanning tetraether lipids from Thermoplasma acidophilum form a monolayer of a constant thickness of 2.5-3.0 nm no matter from which solvent. This finding corresponds to the results of Gliozzi et al. for the lipids of another archaebacterium, Sulfolobus solfataricus. Black lipid membranes were formed at room temperature with a torus from bilayer-forming lipids, however, the torus could also be formed by the tetraether-lipid itself at room temperature and at defined concentration. In these stable black lipid membranes, conductance was measured in the presence of valinomycin, nonactin, and gramicidin. At 10(-7) M concentration, valinomycin mediated higher conductance in membranes from tetraether lipids (200-1200 microS/cm2) than from bilayer-forming lipids (125-480 microS/cm2). Nonactin, at 10(-6) M concentration, mediated a 6-fold higher conductance in a tetraether lipid membrane than in a bilayer, whereas conductance, in the presence of 5 x 10(-11) M gramicidin could reach higher values in bilayers than in tetraether lipid monolayers of comparable thickness. Monensin did not increase the conductance of black lipid membranes from tetraether lipids under all conditions applied in our experiments. Poly(L-lysine) destroyed black lipid membranes. Lipopolysaccharides from Thermoplasma acidophilum were not able to form stable black lipid membranes by themselves. The lipopolysaccharide complexes from Thermoplasma acidophilum and from Escherichia coli decreased the valinomycin-mediated conductance of monolayer and bilayer membranes. This influence was stronger than that of the polysaccharide dextran. PMID- 1420296 TI - Phospholipid modifications during conversion of hepatic myofibroblasts into lipocytes (Ito-cells). AB - Connective tissue cells of liver parenchyma (perisinusoidal myofibroblasts) can be induced to express the lipocyte (Ito cell) phenotype. We have studied phospholipid synthesis and phosphate incorporation during this in vitro conversion, induced by insulin and/or indomethacin, in the established murine cell line GRX. Phospholipid synthesis, measured by [14C]acetate incorporation, was increased after a full induction of the lipocyte phenotype. The 32Pi incorporation into phospholipids was increased from the beginning of induction. Phosphatidic acid and phosphatidylinositol synthesis were increased early in the induction, whilst the increase of major constitutive phospholipids was significant only after the full lipocyte phenotype induction. The presence of unsaturated fatty acids in phospholipids was increased in lipocytes. Linoleic acid was present only in diacylglycerols and in phosphatidylinositol. Since we have shown previously that linoleic acid was not present in triacylglycerols, this result indicates the importance of future studies on activation of phosphatidylinositol cycles in induction of lipocyte phenotype in liver connective tissue cells. PMID- 1420297 TI - Interaction between high-density lipoprotein subpopulations in apo B-free and abetalipoproteinemic plasma. AB - Two populations of high-density lipoprotein (HDL) particles exist in human plasma. Both contain apolipoprotein (apo) A-I, but only one contains apo A-II: Lp(AI w AII) and Lp(AI w/o AII). To study the extent of interaction between these particles, apo B-free plasma prepared by the selective removal of apo B containing lipoproteins (LpB) from the plasma of three normolipidemic (NL) subjects and whole plasma from two patients with abetalipoproteinemia (ABL) were incubated at 37 degrees C for 24 h. Apo B-free plasma samples were used to avoid lipid-exchange between HDL and LpB. Lp(AI w AII) and Lp(AI w/o AII) were isolated from each apo B-free plasma sample before and after incubation and their protein and lipid contents quantified. Before incubation, ABL plasma had reduced levels of Lp(AI w AII) and Lp(AI w/o AII), (40% and 70% of normals, respectively). Compared to the HDL of apo B-free NL plasma, ABL HDL had higher relative contents of free cholesterol, phospholipid and total lipid, and contained more particles with apparent hydrated Stokes diameter in the 9.2-17.0 nm region. These differences were particularly pronounced in particles without apo A-II. Despite their differences, the total cholesterol contents of Lp(AI w AII) increased, while that of Lp(AI w/o AII) decreased in all five plasma samples and the amount of apo A-I in Lp(AI w AII) increased by 6-8 mg/dl in four during the incubation. These compositional changes were accompanied by a relative reduction of particles in the 7.0-8.2 nm Stokes diameter size region and an increase of particles in the 9.2-11.2 nm region. These data are consistent with intravascular modulation between HDL particles with and without apo A-II. The observed increase in apo A II-associated cholesterol and apo A-I, could involve either the transfer of cholesterol and apo A-I from particles without apo A-II to those with A-II, or the transfer of apo A-II from Lp(AI w AII) to Lp(AI w/o AII). The exact mechanism and direction of the transfer remain to be determined. PMID- 1420298 TI - The phosphonic acid analog of phosphatidylglycerol phosphate: influence on Escherichia coli growth and physiology. AB - At 20 microM, rac-3,4-dihydroxybutyl-1-phosphonate (DBP) has only a slight bacteriostatic effect on Escherichia coli. However, cells lose viability when the medium also contains either 20 mM magnesium or calcium ions. Magnesium ions stimulate the incorporation of DBP into (1,2-diacyl)-sn-glycerol-D-4' phosphoryloxy-3'-hydroxybutyl-1'-pho sphonate, the phosphonate analog of phosphatidylglycerol phosphate. Much higher DBP concentrations are needed to block the growth of a pgsA3 mutant than to block the growth of an isogenic wild type strain. The DBP-treated pgsA mutant also has a much higher survival rate when stored in the cold than does the DBP-treated wild-type strain. Furthermore, the pgsA3 mutant grows normally in the presence of DBP and magnesium ions. Treatment with DBP and magnesium ions does not appear to disrupt the cell's inner or outer membranes. However, it does block macromolecular and phosphoglyceride synthesis. A combination of 20 microM rac-DBP and 0.5 mM spermidine or 0.125 mM spermine is bacteriostatic. These studies indicate that the PGP analog contributes to DBP's bacteriostatic effect when the growth medium contains low concentrations of magnesium or calcium ions and is responsible for its bactericidal effect when the medium contains high concentrations of these ions. PMID- 1420300 TI - Essential fatty acid metabolism in cultured human airway epithelial cells. AB - To characterize essential fatty acid metabolism of human airway epithelium, we examined the capacity of epithelial cells to incorporate and desaturate/elongate 18:2(n - 6) and the turnover of phospholipid fatty acyl chains in these cells. Epithelial cells were cultured for 5-7 days and incubated with [1-14C]18:2(n - 6) (1 microCi, 100 nmol). The essential fatty acid profile of the cells was readily modified by 18:2(n - 6) supplementation to culture medium. After 4 h incubation, 32 +/- 5.6 nmol of [1-14C]18:2(n - 6) was incorporated into phospholipids (65 +/- 9.5%, of which 74% was incorporated into phosphatidylcholine (PC)) and neutral lipid (31 +/- 10%) per mg protein of cultured cells. 30 +/- 8% of [1-14C]18:2(n - 6) incorporated, was converted to homologous trienes, tetraenes and pentaenes, the major products being 20:3(n - 6) and 20:4(n - 6). The conversion of 18:2(n - 6) was time-dependent and donor age-related. A higher proportion of 20:3(n - 6) and 20:4(n - 6) was incorporated into phosphatidylinositol (PI) and phosphatidylethanolamine (PE). About 10-15% of total products formed from 18:2(n 6) was released from membrane to culture medium. Both 20:4(n - 6) and 20:5(n - 3) inhibited 18:2(n - 6) incorporation and desaturation. Rate of incorporation of 18:2(n - 6) was more than either 18:1(n - 9) or 16:0. With pulse-chase studies, the half-life of 18:2(n - 6) in PC, PI and PE was estimated to be 5.5, 6.0 and 7.3 h, respectively. These data indicate active metabolism of essential fatty acids in human airway epithelial cells. This metabolism may play a key role in the regulation of membrane properties and function in these cells. PMID- 1420299 TI - LCAT activation properties of apo A-I CNBr fragments and conversion of discoidal complexes into spherical particles. AB - We studied the substrate properties of the phospholipid-cholesterol apolipoprotein complexes generated with apo A-I, apo A-I-CNBr fragments, apo A-II and apo A-IV for cholesterol esterification by the enzyme lecithin-cholesterol acyltransferase (LCAT). The kinetic parameters determined with the different complexes as substrates, showed that the complexes containing apo A-I and apo A IV were about 40-times more efficient than those generated with the apo A-I fragments. In this system, the substrates containing apo A-II had the lowest efficiency. In spite of the differences in the kinetic parameters observed with the various apolipoprotein-lipid complexes, the cholesterol inserted in the complexes was esterified for more than 90% after 24 h in all systems studied. Based upon the results of the kinetic experiments, we followed the transformation of the discoidal complexes into spherical particles, due to the formation of a cholesteryl esters core, in the presence of low-density lipoproteins as an external source of cholesterol. We observed the formation of spherical particles by electron microscopy, after incubation of the discoidal complexes with LCAT for 24 h. The average percentage of cholesteryl esters in the converted particles was around 60% of the total cholesterol, varying between 40% for the apo A-I-CNBr-1 DPPC-cholesterol complex and up to 86% for the apo A-I-DPPC-cholesterol complex. The secondary structure of protein in the complexes was not significantly modified. However, the phospholipid phase transition disappeared, together with the parallel orientation of the phospholipid acyl chains with the helical segments of the apolipoproteins, as the phospholipids are organized in a monolayer at the surface of the spheres. PMID- 1420301 TI - Low temperature-induced fatty acid desaturation in Brassica napus: thermal deactivation and reactivation of the process. AB - When Brassica napus plants are grown at low temperatures (e.g., 5 degrees C) the rate of desaturation in leaves of newly formed fatty acids in both chloroplastic (MGDG) and cytosolic (PC) diacylglycerols is higher or more rapid than in plants grown at higher temperatures (e.g., 30 degrees C). This low temperature-induced increase in the rate of desaturation is lost within hours if plants are transferred to higher temperatures. However, if plants are then returned to low temperatures they regain the ability to rapidly desaturate fatty acids. This process is restored relatively slowly (over days) in contrast to the more rapid loss at high temperatures. This has important physiological consequences on the level of unsaturated fatty acids in plant membranes and the process of temperature control of the fatty acid composition of membrane lipids. PMID- 1420302 TI - Action of lysosomal phospholipase A1 on bis(monoacylglycerol)phosphate. AB - Bis(monoacylglycerol)phosphate (BMP) in macrophages is known to rapidly turn over its acyl moiety(s) located at primary positions of the glycerols, yet the glycerols and phosphate remain stable within the BMP molecule. Here we examine whether the phospholipase A1 isolated from rat-liver lysosomes is capable of deacylating BMP. By comparison with the precursor of BMP, phosphatidylglycerol, BMP is a very poor substrate for the phospholipase A1. We conclude, therefore, that a direct deacylation of the acyl groups at the primary alcohol level of the glycerol probably does not occur, but postulate that transacylations may occur to account for the removal of the acyl moiety. PMID- 1420304 TI - Nitrogen chemical structure in DNA and related molecules by X-ray absorption spectroscopy. AB - The electronic environment of nitrogen in nucleic acid bases, nucleotides, polynucleotides and DNA has been studied, for the first time using X-Ray Absorption Near-Edge Spectroscopy (XANES). Generally, the spectra of these complex molecules consist of low energy bands corresponding to 1s-->pi* transitions and high energy bands corresponding to 1s-->sigma* transition, as illustrated using several nitrogen model compounds. The 1s-->pi* transitions show particular sensitivity to the chemical environment of the nitrogen. Oxygen substitution on ring carbon atoms generally results in a significant blue shift of the lowest 1s-->pi* bands while halogen substitution results in a small blue shift. These observations illustrate the significance of the disturbance of the aromatic ring system produced by exocyclic carbonyl groups. Direct substitution on the nitrogen frequently results in significant spectral perturbations. Differences between the spectra of the polynucleotides and the sums of spectra of the individual nucleotides point to the effects of hydrogen-bonding in complementary double-helix structures. The XANES spectrum of a DNA sample with a known ratio of the polynucleotides is equivalent to the weighted sum of the spectra of individual polynucleotides, indicating that the difference in base stacking interactions produces negligible spectral effects. The variability of nitrogen K-edge spectra in these samples and in protein may be useful for chemically specific imaging using X-ray microscopes. PMID- 1420303 TI - Identification of a developmentally regulated gene in the mouse central nervous system which encodes a novel proline rich protein. AB - A full length cDNA whose corresponding mRNA is down-regulated during the mouse embryonic brain development was isolated. The cDNA contains a single long open reading frame which could encode a protein with relative molecular mass of 41 kDa. The predicted gene product contains long stretches of prolines towards the NH2-terminus, followed by a leucine/proline rich region. The cDNA probe detected a number of mRNA species in Northern blot analysis. The reverse transcriptase polymerase chain reaction analysis of mRNA from adult mouse tissues indicated that heart and testis expressed this gene (named NDPP-1) at relatively high levels, while lower levels of mRNA were detected in a number of other tissues. Expression of NDPP-1 was also detected in embryonic carcinoma and pheochromocytoma cell lines, but not in fibroblasts. The cDNA hybridized to genomic DNA from several vertebrates species in Southern blot analysis indicating interspecies conservation of this gene. The interesting pattern of expression of the NDPP-1 gene during mouse brain development and the structure of its putative protein product indicate that this gene may play an important biological role in the development of mouse central nervous system. PMID- 1420305 TI - Expression of heme oxygenase and its RNA in mouse liver after injection of heme and splenectomy. AB - Heme is known to activate the HO (heme oxygenase) gene in cultured cells, but little is known about the effect of heme on the HO gene in intact organisms. The expressions of HO and its RNA in mouse liver were measured using mouse HO cDNA and HO antibody after injection of heme or splenectomy. The antibody was prepared against a beta-galactosidase-HO hybrid protein made in Escherichia coli. The HO mRNA level increased to a maximum 15 h after heme injection. In contrast, expression of HO was maximal about 45 h after heme injection. Essentially the same results were obtained in mice after splenectomy. These results suggest that the HO gene in mouse liver was activated by the injection of heme and splenectomy. PMID- 1420306 TI - Structural organization of a nuclear gene for the alpha-subunit of the bovine mitochondrial ATP synthase complex. AB - The structural organization of an expressed bovine gene (ATPA1) that encodes an isoform of the alpha-subunit of the mitochondrial F0F1 ATP synthase was determined. The gene extends over 10 kilobase-pairs and is divided into 12 exons. The first exon encodes the 5' untranslated region and approximately one-half of the presequence that targets this protein to the mitochondrion. The remainder of the presequence, together with three amino acids of the mature protein, are encoded by exon 2. Primer extension and nuclease protection analyses revealed multiple sites of transcription initiation. The 5' flanking region of the ATPA1 gene can drive the transcription of a reporter gene in an orientation-dependent manner. This promoter region contains several sequence elements which might play an important role in regulating the expression of this gene, including possible TATA and CCAAT boxes, putative Sp1-binding sites, and sequences resembling AP-1, AP-2, AP-4 and cAMP-responsive elements. The ATPA1 gene also contains sequences homologous to several motifs that are shared among some nuclear genes encoding mitochondrial proteins. These include Mt1, Mt3, Mt4, a respiratory enhancer, and NRF-2 sites. Tissue-specific differences in the ATPA1 mRNA levels were observed with high levels found in skeletal muscle and heart, and lower levels in other tissues. PMID- 1420307 TI - In vitro expression and secretion of functional mammalian intrinsic factor using recombinant baculovirus. AB - Intrinsic factor was produced at levels of 1-2 mg per 1 (0.25 micrograms per 10(6) cells) by growth of recombinant baculovirus-infected Sf9 cells in spinner culture. The recombinant IF showed a binding affinity for cobalamin (2.6.10(-10) M) and for the intrinsic factor-cobalamin receptor (3.5.10(-10) M) nearly identical with native IF. Purification of the recombinant intrinsic factor could be accomplished by affinity chromatography, but final purification by gel chromatography (FPLC) was necessary to separate intrinsic factor from a 62 kDa protein secreted from uninfected Sf9 cells. This protein binds selectively to the cobalamin-Sepharose column, but demonstrates no cobalamin binding activity after elution. Microgram quantities of radiolabelled protein could be produced for metabolic and autoradiographic studies. The stability of intrinsic factor to pancreatic proteinases was nearly identical with human gastric intrinsic factor, both native and recombinant as produced in mammalian cells. Glycosylation of the intrinsic factor was demonstrated by lectin binding to the recombinant protein separated on SDS-PAGE, and by a shift in apparent molecular mass from 47 kDa to 43 kDa following treatment of Sf9 cells with tunicamycin. Most of the recombinant IF was produced by Sf9 cells in the first 48 h post infection. PMID- 1420308 TI - Binding of GDP to a ribosomal protein after elongation factor-2 dependent GTP hydrolysis. AB - Incubation of 80S ribosomes with a substoichiometric amount of [alpha-32P]GTP and with eEF-2 resulted in the specific labeling of one ribosomal protein which migrated very close to the position of the acidic phosphoprotein P2 from the 60S subunit in two-dimensional isofocusing-SDS gel electrophoresis. Localization of protein P2 in this electrophoretic system was ascertained by correlation with its position in the standard two-dimensional acidic-SDS gel electrophoresis after its specific phosphorylation by casein kinase II. Labeling of the ribosomal protein was dependent on the presence of eEF-2, and could be attributed to [alpha-32P]GDP binding from the results of chase experiments and HPLC identification, this binding being very likely responsible for the slight shift in the electrophoretical position of the protein. Incubation of ribosomes with tRNA(Phe) in the absence of mRNA induced the release of the bound GDP. PMID- 1420309 TI - Regulation of translation and proteolysis during the development of embryonic dorso-ventral polarity in Drosophila. Homology of easter proteinase with Limulus proclotting enzyme and translational activation of Toll receptor synthesis. AB - The generation of dorso-ventral polarity during Drosophila embryogenesis is regulated by the action of 12 maternally expressed gene products, the dorsal group. These products act together to form a dorso-ventral nuclear gradient of the transcription factor dorsal. At least three of the dorsal group genes (snake, easter and gastrulation defective) encode secreted serine proteinases which probably function during early development in the perivitelline compartment of the embryo. Here, we report that the easter proteinase is homologous in its light chain sequence to the haemocyte proclotting enzyme (PCE) of the Japanese horseshoe crab Tachypleus tridentatus. PCE is the terminal member of a proteolytic cascade activated in response to microbial polysaccharides and acts to cleave coagulogen, an invertebrate equivalent of fibrinogen. On the basis of this homology we are able to predict with confidence the overall primary structure of the easter proteinase, its mode of activation and its substrate specificity. The result also suggests that easter functions zygotically in haemocytes in a Drosophila defence response analogous to that found in Tachypleus. We also show here that the Toll receptor protein is absent in early cleavage embryos but accumulates rapidly at the syncitial blastoderm stage, the developmental stage at which its function is required. This finding suggests that translation of Toll mRNA is regulated in response to fertilisation and egg deposition. These two observations are consistent with a model of dorso-ventral pattern formation in which a proteolytic cascade is activated uniformly in the perivitelline compartment of the embryo and causes the release of ventrally localised ligands of the Toll receptor. A possible alternative model in which a proteolytic cascade is activated in response to a ventrally restricted signal is also discussed. PMID- 1420311 TI - Unusual sequences of two old, inactive human Alu repeats. AB - Two human Alu repeats terminating in an oligo(T) run rather than the usual A-rich 3' tail were isolated by library screening. Base sequence comparisons reveal that these unusual Alus are also exceptionally divergent from other Alu family members implying that they are evolutionarily old. Unlike other members of the family, they are not transcribed in vitro by RNA polymerase III (Pol III) suggesting a partial explanation for how Alu source genes might become inactive with age. PMID- 1420310 TI - Isolation of cDNA clone encoding rat senescence marker protein-30 (SMP30) and its tissue distribution. AB - We have isolated and characterized two cDNA clones encoding senescence marker protein-30 (SMP30), the amounts of which are known to decrease androgen independently with aging in the livers of rats. Of these cDNA clones, one consisted of 1588 bp nucleotides and the other of 1195 bp nucleotides generated by alternative polyadenylation. These two cDNA clones shared the same open reading frame, but the larger species had 393 bp nucleotides of 3' untranslated region in addition to the first polyadenylation site of smaller species. Northern hybridization analysis showed that two species of mRNA (1.7 kb and 1.4 kb) located in the liver and kidney were consistent with these short and long forms of cDNA. The open reading frame, 897 bp could encode 299 amino acids. The estimated molecular weight and pI of the deduced polypeptide were 33,387 and 5.1, respectively. Furthermore, immunohistochemical analysis confirmed that SMP30 was preferentially localized in the hepatocytes and renal proximal tubular epithelium. Genomic Southern hybridization analysis demonstrated that SMP30 was widely conserved among higher animals. A computer-assisted homology analysis of nucleic acid and protein databases revealed no remarkable homology with other known proteins. Therefore, SMP30 seems to be a novel protein. In addition, the existence of putative A-U rich mRNA degradation signals and protein degradation signals (PEST sequence) in the structure of SMP30 may suggest important regulatory function of this unique protein manifested by changes in its concentrations. PMID- 1420312 TI - Improved plasmids containing the Escherichia coli dam gene under the control of the tac promoter. AB - We report the construction of a series of plasmids containing the dam gene under the control of the tac promoter. Cells containing these plasmids produce about 8 to 10-fold more Dam methyltransferase (Mtase) than the previously used plasmid pTP166 and avoid the use of a high temperature step necessary for the expression of Dam Mtase in the plasmid pDOX1 and thus allow its use for the study of thermosensitive mutants. PMID- 1420313 TI - Primary structure of rat renal dipeptidase and expression of its mRNA in rat tissues and COS-1 cells. AB - Three cDNA clones of rat renal dipeptidase (rrDP) were isolated from rat renal and pulmonary cDNA libraries using a DNA fragment of human renal DP cDNA clone, MDP4, as a probe. The complete amino acid sequence deduced from the cDNA contains 410 amino acid residues, beginning with a signal peptide of 16 amino acid residues. RNA blot hybridization analysis showed that 1.6 and 2.2 kb mRNAs were expressed in lung and kidney, however, only 1.6 kb mRNA was detected in small intestine. COS-1 cells transfected with the cDNA expressed enzymatically active rrDP. PMID- 1420314 TI - The complete cDNA sequence for dihydrolipoyl transacylase (E2) of human branched chain alpha-keto acid dehydrogenase complex. AB - We have determined the complete nucleotide sequence for the cDNA encoding human dihydrolipoyl transacylase (E2) using the rapid amplification of cDNA ends (RACE) procedure. The full-length E2 cDNA is 3535 nucleotides in length. The coding region spans 1446 bp and the 3'-noncoding region spans 2074 bp. The latter contains three Alu repetitive sequences and two transcription termination sites. PMID- 1420315 TI - Nucleotide sequence and tissue distribution of mouse transforming growth factor alpha. AB - Transforming growth factor-alpha (TGF alpha) is secreted into the medium of the Moloney murine sarcoma virus-transformed 3T3 cell line, 3B11-1C. Using reverse transcription-polymerase chain reaction (RT-PCR), we have amplified, cloned and sequenced a cDNA fragment from this cell line which encodes the full protein coding region of the mouse TGF alpha precursor. The deduced amino acid sequence (159 residues) differs from that of human TGF alpha at 13 sites and from that of rat at 3 sites. In the mouse, TGF alpha transcripts were detected in a variety of normal adult tissues including two previously unreported sites: the preputial glands and the bladder. PMID- 1420316 TI - Sequencing of the primary adhesion domain of bovine von Willebrand factor. AB - A cDNA library, constructed from bovine heart endothelial cell poly(A)+ RNA, was screened using a BstXI fragment of human von Willebrand and factor (vWF) cDNA as a probe. This probe codes for the major adhesion domain of vWF that includes the GPIb, collagen and heparin binding domains. Of the ten positive clones obtained, a clone that spanned the region of interest was sequenced by the dideoxynucleotide method yielding a sequence of 1550 bp. This region of the bovine cDNA codes for amino acids corresponding to #262 to #777 in human vWF and encompasses the entire pro adhesion domain. Both the nucleotide sequence and the deduced amino acid sequence are 82% homologous to those of human vWF. Cysteine residues #471, 474, 509 and 695, which form intrachain bonds in human vWF, are also present in the bovine vWF sequence. PMID- 1420317 TI - A new cDNA sequence for the murine interleukin-2 gene. AB - We have amplified by PCR and sequenced the first exon of the interleukin 2 gene from the RF/J mouse strain DNA. When we compared the RF/J first exon sequence with the one reported previously, we found several differences. These differences are also reflected in the deduced amino acid sequence and they have been localized in the first 23 amino acids of the mature polypeptide. The finding of this new IL-2 sequence shows that there is more than one allele for the mouse IL 2 molecule and raises the possibility of functional differences between alleles. PMID- 1420318 TI - Cloning and 5'-flanking sequence of a rat cholesterol 7 alpha-hydroxylase gene. AB - A cholesterol 7 alpha-hydroxylase gene containing 8 kb of the 5'-flanking region and 5 kb of the transcription region which covers exons 1 to 5 was isolated from a rat genomic library. The 2015 bp nucleotide sequence 5'-upstream from the start codon was determined. This promotor region contains many liver-enriched or specific elements (TGT3, HNF/LF-B1), putative hormone responsive elements (TRE, GRE, RRE or RARE) and ubiquitous transcription factor binding sites (NF-1, OCT 1). In addition, 21 CA repeats which have potential to form the Z-DNA structure were found in this region. These putative regulatory elements and repetitive motifs may play roles in the regulation of cholesterol 7 alpha-hydroxylase gene in the liver. The sequence identity of the rat gene to the human gene in this region is low. Only liver-enriched elements are conserved in the cholesterol 7 alpha-hydroxylase genes. PMID- 1420319 TI - Secretagogue-induced proteolysis of lung spectrin in alveolar epithelial type II cells. AB - Incubation of isolated rat alveolar epithelial type II cells with secretagogues (calcium ionophore, ATP or terbutaline) resulted in rapid proteolysis of lung spectrin and appearance of multiple proteolytic products which showed immunoreactivity with an antibody against human erythrocyte spectrin. These proteolytic products were similar to those generated from erythrocyte spectrin or cultured lung tumor cells (A549 cells) incubated with purified calpain. Furthermore, incubation of alveolar type II cells with a calpain-specific inhibitor modulated the secretagogue-induced proteolysis of lung spectrin. Thus, stimulation of secretion appeared to activate endogenous calpain in type II cells, suggesting that calpain-mediated proteolysis of a submembranous cytoskeletal protein could play an important role in the secretory process. PMID- 1420320 TI - Cultured chick-embryo heart cells respond differently to ouabain as measured by the increase in their intracellular Na+ concentration. AB - Using digital imaging microscopy with the sodium-sensitive fluorescent indicator sodium-binding benzofuran isophtalate (SBFI), we examined the cytosolic free sodium ion concentration ([Na+]i) in single chick-embryo heart cells. The distribution of the [Na+]i was homogeneous within one cell, but we found a wide cell to cell variation in the range of 3 to 18 mM [Na+]i. In contrast to former experiments showing a heterogeneity of chick-embryo heart cells with respect to their [Ca2+]i (Ahlemeyer et al. (1992) Eur. J. Biochem. 205, 269-275), we could not distinguish cell populations with different [Na+]i. We found a lognormal distribution of the resting [Na+]i with a median value of 8.8 mM with a standard deviation of 4.5 mM (n = 90). After the addition of varying concentrations of ouabain, we found a biphasic dose-response curve as measured by the increase in [Na+]i. Ouabain showed its half-maximal effect on the [Na+]i between 10(-9) M and 10(-8) M and at 4.3.10(-6) M under steady-state conditions. The finding of a heterogeneity of chick-embryo heart cells with respect to their ouabain-induced increase in [Na+]i is consistent with our previous observations of cells differing in their [Ca2+]i and in the sensitivity of their sodium pumps to cardiac glycosides. PMID- 1420321 TI - Transferrin and iron distribution in subcellular fractions of K562 cells in the early stages of transferrin endocytosis. AB - Iron distribution in subcellular fractions was investigated at different times after a single cohort of 59Fe-125 I-labeled transferrin (Tf) endocytosis in K562 cells. Cell homogenates prepared by hypotonic lysis and deoxyribonuclease (DNAase) treatment were fractionated on Percoll density gradients. Iron containing components in the postmitochondrial supernatant were further fractionated according to their molecular weight using gel chromatography and membrane filtration. In the initial phases of endocytosis, both iron and Tf were found in the light vesicular fraction. After 3 min the labels diverged, with iron appearing in the postmitochondrial supernatant and Tf in the heavy fraction containing mitochondria, lysosomes and nuclei. Iron released from Tf-containing vesicles appeared both in low- and high-molecular-weight fractions in the postmitochondrial supernatant. After 5 min of endocytosis 59Fe activity in the low-molecular-weight fraction remained constant and 59Fe accumulated in a high molecular-weight fraction susceptible to desferrioxamine chelation. After 10 min, 59Fe radioactivity in this fraction decreased and a majority of cytosolic 59Fe was found in ferritin. These results do not support the concept of the cytosolic low-molecular-weight iron pool as a kinetic intermediate between transferrin and ferritin iron in K562 cells. PMID- 1420322 TI - Iron(III)-binding polypeptide in human cord and adult serum: isolation, purification and partial characterization. AB - A low-molecular-weight, non-transferrin-bound, Fe(III)-binding polypeptide has been isolated and purified from normal human cord and adult sera by gel filtration and high-performance liquid chromatography. The polypeptide was traced isotopically with 59Fe(III)-chloride and high voltage paper electrophoresis. This Fe(III)-binding polypeptide has been partially characterized, and found to be biochemically distinct from other known Fe(III)-binding proteins, such as transferrin, lactoferrin and ferritin. Furthermore, the electrophoretic mobility and amino-acid composition distinguish the polypeptide from other physiological iron chelators such as a previously described Fe(III)-citrate complex. The polypeptide is highly hydrophilic, rich in lysine residues and phosphorylated. The observed positive charge of the polypeptide is suggested to originate from these lysine residues. The molecular mass of this polypeptide is estimated to be approx. 2500 Da, which is in close agreement with previous reports and is consistent with amino-acid analysis data. Cord serum levels of the polypeptide were significantly higher than adult serum levels. The degree of Fe(III) specificity and the function of the Fe(III)-polypeptide have not been ascertained at the present time. It is possible that the polypeptide may compete for Fe(III) with transferrin and is involved in the mobilization and transportation of iron by some as yet unknown mechanism. PMID- 1420323 TI - Poly(ADP-ribosyl)ation of chromatin in an in-vitro poly(ADP-ribose)-turnover system. AB - This paper describes the effect of an in-vitro poly(ADP-ribose) turnover system on the poly(ADP-ribosyl)ation of chromatin. Both poly(ADP-ribose)polymerase and poly(ADP-ribose)glycohydrolase were highly purified and used in 4 different turnover systems: non-turnover, slow, medium and fast turnover. These turnover systems were designed to reflect possible turnover conditions in intact cells. The major protein acceptors for poly(ADP-ribose) are histones and the polymerase itself, a process referred to as automodification. The level of poly(ADP-ribose) modification of polymerase, histone H1 and core histones has been measured. The size of the polymer for each of the 3 groups of acceptor proteins has been determined by gel electrophoresis. After many turnover cycles at medium and fast turnover, the histones (H1 and core) become the main poly(ADP-ribose) acceptor proteins. The rate at which steady-state polymer levels are reached and the total accumulation of polymer in a given turnover system are both inversely proportional to the amount of glycohydrolase present. Furthermore, increasing amounts of glycohydrolase in the turnover systems reduces average polymer size. The polymer synthesized in the medium and fast turnover systems is degraded by glycohydrolase in a biphasic fashion and in these systems the half-life of polymer agreed with results found in intact cells. Our results show that the relative levels of polymerase and glycohydrolase activities can regulate the proportional poly(ADP-ribose) distribution on chromatin-associated acceptor proteins during steady-state turnover conditions. The patterns of modification of polymerase and histones under turnover conditions agree with in vivo observations. PMID- 1420324 TI - Insulin effect on isolated rat hepatocytes: diacylglycerol-phosphatidic acid interrelationship. AB - It is widely accepted that insulin action does not involve inositol phospholipid hydrolysis through the stimulation of a phosphatidylinositol-specific phospholipase C (PI-PLC). This consideration prompted us to investigate the insulin effect on the mechanism leading to the accumulation of diacylglycerol (DAG) and phosphatidic acid (PA) in rat hepatocytes. Basically, insulin induces: (i) a significant increase of both [3H]glycerol and fatty acid labelling of DAG; (ii) a significant increase of PA labelling preceding DAG labelling and paralleled by a decrease of phosphatidylcholine (PC) labelling. These observations, which suggest an insulin-dependent involvement of a phospholipase D, are strengthened by the increase of PC-derived phosphatidylethanol in presence of ethanol. Finally, the observation that the PA levels do not return to basal suggests that other mechanisms different from PC hydrolysis, such as the stimulation of direct synthesis of PA, may be activated. PMID- 1420325 TI - The mitochondrial carnitine carrier: characterization of SH-groups relevant for its transport function. AB - The transport function of the purified and reconstituted carnitine carrier from rat liver mitochondria was correlated to modification of its SH-groups by various reagents. The exchange activity and the unidirectional transport, both catalyzed by the carnitine carrier, were effectively inhibited by N-ethylmaleimide and submicromolar concentrations of mercurial reagents, e.g., mersalyl and p (chloromercuri)benzenesulfonate. When 1 microM HgCl2 or higher concentrations of the above mentioned mercurials were added, another transport mode of the carrier was induced. After this treatment, the reconstituted carnitine carrier catalyzed unidirectional substrate-efflux and -influx with significantly reduced substrate specificity. Control experiments in liposomes without carrier or with inactivated carrier protein proved the dependence of this transport activity on the presence of active carnitine carrier. The mercurial-induced uniport correlated with inhibition of the 'physiological' functions of the carrier, i.e., exchange and substrate specific unidirectional transport. The effect of consecutive additions of various reagents including N-ethylmaleimide, mercurials, Cu(2+)-phenanthroline and diamide on the transport function revealed the presence of at least two different classes of SH-groups. N-Ethylmaleimide blocked the carrier activity by binding to SH-groups of one of these classes. At least one of these SH-groups could be oxidized by the reagents forming S-S bridges. Besides binding to the class of SH-groups to which N-ethylmaleimide binds, mercurials also reacted with SH-groups of the other class. Modification of the latter led to the induction of the efflux-type of carrier activity characterized by loss of substrate specificity. PMID- 1420326 TI - Protein sequence determination by ESI-MS and LSI-MS tandem mass spectrometry: parvalbumin primary structures from cat, gerbil and monkey skeletal muscle. PMID- 1420327 TI - Disulfide-linked S100 beta dimers and signal transduction. AB - S100 beta is a calcium-binding protein with neurotrophic and mitogenic activities, both of which may be mediated by the protein's ability to stimulate an increase in intracellular free calcium ([Ca2+]i). These extracellular trophic activities of S100 beta require a disulfide-linked, dimeric form of the protein. In this chapter, we present a minireview on the current state of knowledge concerning extracellular functions of S100 beta, with emphasis on the potential relevance of these activities to neuropathological disorders. We also report a simplified procedure for preparation of pharmacological amounts of biologically active S100 beta dimers, based on the finding that formation of disulfide-linked S100 beta dimers can be stimulated by the presence of calcium or lipid. PMID- 1420328 TI - Ca(2+)-calmodulin regulated effectors of microtubule stability in neuronal tissues. AB - In general, microtubules are labile structures which depolymerize at low temperature and are sensitive to Ca2+. However, in brain tissue, axonal microtubules are disassembly-resistant and can exist without attachment to a microtubule organizing center. Stable microtubules cannot be purified by usual recycling procedures and this has made the elucidation of the molecular mechanisms involved in their stabilization difficult. This paper summarizes previous work in our laboratories, aimed at the identification of brain microtubule stabilizing proteins. We present assay methods which allow the detection of microtubule stability effectors in complex extracts and in chromatographic column fractions. Applied to brain crude extracts, they result in the isolation of Ca(2+)-calmodulin binding and Ca(2+)-calmodulin regulated proteins. One, called STOP, appears to account for microtubule stabilization in neurons. A second protein with similar activity is myelin basic protein. Non neuronal tissues also contain Ca(2+)-calmodulin-regulated effectors which appear to differ in structure from their neuronal counterparts. Thus, in all tissues examined, microtubule stability seems to be accounted for by unique Ca(2+) calmodulin regulated proteins, showing tissue specificity. PMID- 1420329 TI - A growth-dependent post-translational modification of annexin VI. AB - Annexin VI (p68, 67-kDa calelectrin) is a member of a family of Ca2+/phospholipid binding proteins, that includes p35 (annexin I) and p36 (annexin II), the major cellular substrates for phosphorylation by the epidermal growth factor receptor and pp60v-src tyrosine kinase activities, respectively. We report here that like annexins I and II, annexin VI is phosphorylated in vivo, but that in contrast, annexin VI phosphorylation is associated with cell growth. In both Swiss 3T3 fibroblasts and human T-lymphoblasts the pattern of phosphorylation followed an almost identical profile. In particular, annexin VI was not phosphorylated in quiescent cells, but was phosphorylated on serine and to a lesser extent threonine, several hours following cell stimulation. Furthermore, annexin VI also incorporated phosphate in a growth-dependent manner, in a form other than a phosphoamino-acid. The phosphate was visualised following acid hydrolysis of immunoprecipitated annexin VI, as part of a complex having high mobility on 2-D thin-layer electrophoresis. The identity of this complex is not known. The results suggest that a post-translational modification other than direct protein phosphorylation may influence the activity of annexin VI and provide evidence linking cell growth with regulation of annexin VI function. PMID- 1420330 TI - The alpha-helical content of calmodulin is increased by solution conditions favouring protein crystallisation. AB - The conformation of porcine-brain calmodulin in solution has been examined by far UV circular dichroism in the presence of 2-methyl 2,4-pentanediol, and polyethylene glycol which are used to promote the crystallisation of calmodulin. These organic compounds increase the alpha-helical content of Ca4-calmodulin to a significant degree and to a level similar to the alpha-helical content deduced from the crystal structure. These results support the view that in aqueous solution at pH 5-7, the conformation of Ca4-calmodulin is significantly different from the crystal structure and probably lacks at least a portion of the central helix. In the process of crystallisation, Ca4-calmodulin apparently adopts additional alpha-helical structure, probably due to the composition of the solution from which crystals are grown. PMID- 1420331 TI - Interaction of calmodulin with phospholamban and caldesmon: comparative studies by 1H-NMR spectroscopy. AB - In order to identify comparative aspects of the interaction of calmodulin with its target proteins, proton magnetic-resonance studies of complex formation between calmodulin and defined segments of phospholamban and caldesmon have been undertaken. Residues 3-15 in the cytoplasmic region of phospholamban, an integral membrane protein of cardiac sarcoplasmic reticulum believed to regulate the calcium pumping ATPase, are shown to contribute to interaction with calmodulin. Using wheat germ calmodulin specifically modified with a spin-label to provide the spectral means for spatial localisation, these residues of phospholamban were correlated with binding in the vicinity of the probe attached to Cys-27 in the N terminal domain of calmodulin. This interaction, relevant to the mechanism of calmodulin-dependent phosphorylation of phospholamban that relieves its inhibitory influence on the calcium pump, provides a useful model system for comparative study of the properties of calmodulin-binding domains. We contrast here a calmodulin-binding segment in the C-terminal region of caldesmon localised by 1H-NMR study of the interface(s) between the two proteins. These observations are discussed in the context of other calmodulin-binding sequences. PMID- 1420332 TI - Interaction of troponin I and troponin C: use of the two-dimensional transferred nuclear Overhauser effect to determine the structure of a Gly-110 inhibitory troponin I peptide analog when bound to cardiac troponin C. AB - The structure of a peptide analog of the inhibitory region of cardiac troponin-I (N-acetyl-G110-TnI(104-115) amide) when bound to cardiac troponin-C has been determined by 2-dimensional 1H-NMR techniques. The bound structure determined for this peptide is similar to that determined previously for the skeletal peptide (which has a proline at position 110) bound to skeletal troponin-C (Campbell and Sykes (1991) J. Mol. Biol. 222, 405-421). This structure shows a helical like peptide backbone 'bent' around P109-G110 to bring the hydrophobic residues F106, L111 and V114 closer together. The other 'side' of this structure is surrounded by the basic residues extending outwards towards the protein or solution. While the bound structures of the cardiac and skeletal peptides are shown to be quite similar, the cardiac peptide appears more flexible near the central glycine residue. PMID- 1420333 TI - Sequence comparison among muscle-specific calpain, p94, and calpain subunits. AB - While conventional calpains, m- and mu-calpains named according to their calcium dependence, are expressed in almost every tissues, mRNA of newly identified p94, which has a significant sequence similarity to the conventional calpain large subunits, is abundantly expressed only in skeletal muscle. In addition to this specific expression, p94 is distinct from conventional calpains in that it contains three unique regions showing no similarity to conventional calpain subunits. When rat and human p94 are compared, overall sequence similarity is 94.0%, which is close to those for m- and mu-calpain large subunits; 93.1% and 95.4% between human and rabbit, respectively, suggesting the evolutionary importance of p94. These calpain large subunit proteins, p94, m- and mu-types, can be considered to constitute a super family, whose p94, m- and mu-types represent the three major types. Sequences of the calpain large-subunit family members, including the recently reported Schistosoma calpain, are compared. Their evolutionary correlation and function are discussed on the basis of the results thus far obtained. PMID- 1420334 TI - S-100 protein binds to annexin II and p11, the heavy and light chains of calpactin I. AB - S-100 protein, a dimeric, Ca(2+)-binding protein of the EF-hand type, interacts with annexin II (p36, the heavy chain of the cytoskeletal protein complex, calpactin I), with p11 (the light and regulatory chain of calpactin I) and with the hetero-tetramer annexin II2-p11(2) (calpactin I) in a Ca(2+)-regulated way, but not with annexins I, V and VI. The interaction of S-100 protein with the above proteins was investigated by fluorescence spectroscopy using acrylodan-S 100 protein and acrylodan-annexin II and by cross-linking experiments using the bifunctional cross-linker disuccinimidyl suberate (DSS). S-100 protein binds with the highest affinity to annexin II (Kd approx. 0.4 microM) and with the lowest affinity to calpactin I (Kd approx. 10 microM), with a constant stoichiometry of about 2 mol of protein/S-100 dimer. Thus, S-100 protein could substitute for p11 in regulating the activities of annexin II in cells which do not express p11 and/or act synergistically with p11 in cells expressing both p11 and S-100. The binding of S-100 protein to p11 could reflect the natural tendency of S-100 subunits and p11 to dimerize. Chimeric p11-S-100 alpha and p11-S-100-beta proteins could therefore form in a Ca(2+)-regulated way. The interaction of S-100 protein with calpactin I appears of doubtful physiological importance, because of the low binding affinity, of the small extent of fluorescence changes induced by calpactin I in acrylodan-S-100 protein and of lack of DSS-induced complex formation between the two protein species. PMID- 1420335 TI - Novel isoforms of CaBP 33/37 (annexin V) from mammalian brain: structural and phosphorylation differences that suggest distinct biological roles. AB - Two calcium-dependent phospholipid- and membrane-binding proteins have been purified from bovine brain. These are termed CaBP33 and CaBP37. Complete sequence analysis has revealed that these two proteins are isoforms of annexin V. Despite an apparent difference of 4 kDa between the two proteins on SDS-PAGE, only two amino-acid substitutions were found. These are, in CaBP33, Ser-36 and Lys-125 and in CaBP37, Thr-36 and Glu-125. This corresponds to a mass difference of 15 Da. This was confirmed by electrospray mass spectrometric analysis. Both isoforms can be phosphorylated substoichiometrically in vitro by protein kinase C at residue Thr-22. PMID- 1420336 TI - The heterodimer calmodulin: myosin light-chain kinase as a prototype vertebrate calcium signal transduction complex. AB - The heterodimer complex of calmodulin (CaM) and the protein kinase catalytic subunit of myosin light chain kinase from vertebrate smooth muscle and non-muscle tissues (sm/nmMLCK) is one of the most extensively characterized CaM-regulated enzyme complexes and it has an established in vivo role in the transduction of calcium signals into biological responses. We have used a combination of approaches to the study of CaM and sm/nmMLCK in order to derive initial insight into the key features of each protein and of the CaM-MLCK heterodimeric complex that are involved in protein-protein and calcium-protein recognition and regulation of enzyme activity. On-going studies are described here that include site-specific mutagenesis, fluorescence spectroscopy, enzymology and peptide analog analysis. These and previous results indicate that: (1), both electrostatic and hydrophobic features are important in the functionally correct interactions between CaM and MLCK; (2), even the interactions between CaM and peptide analogs of the CaM binding site of MLCK are heterogeneous and non-trivial in nature; (3), amino-acid residues that have been conserved in CaM across millions of years of evolution and that are conserved in CaMs with quantitative MLCK activator activity can be mutated without any detectable effect on activity and (4), structures different from the prototypical EF-hand domain of CaM can have similar calcium-binding activity in the presence of a CaM binding structure. PMID- 1420337 TI - Calretinin in rat ovary: an in situ hybridization and immunohistochemical study. AB - Calretinin is a cytosolic calcium-binding protein of the calmodulin superfamily, with high homology with calbindin D28k. The only cells in which calretinin has been described so far are neurons, in the central nervous system and in retina. In the present work, we describe the expression of the calretinin gene in the interstitial cells of rat ovary. Immunohistochemistry, using a calretinin specific antibody, allowed to detect the protein from 19 days after birth. Western blot from ovary homogenates confirmed the labelling of a 29 kDa band, the size of calretinin. In situ hybridization confirmed immunochemical data; calretinin transcripts were clearly shown in the same cell population. This represents the first description of calretinin outside the nervous system. Its function in ovary remains to be determined. PMID- 1420338 TI - Oxylipin pathway to jasmonates: biochemistry and biological significance. PMID- 1420339 TI - Effects of mevinolin treatment on tissue dolichol and ubiquinone levels in the rat. AB - Rats were treated with mevinolin by intraperitoneal injection (15 days) or dietary administration (30 days). The cholesterol, dolichol, dolichyl phosphate and ubiquinone contents of the liver, brain, heart, muscle and blood were then investigated. The cholesterol contents of these organs did not change significantly, with the exception of muscle. Intraperitoneal administration of the drug increases the amount of dolichol in liver, muscle and blood and decreases the dolichyl-P amount in muscle. The same treatment increases the level of ubiquinone in muscle and blood and decreases this value in liver and heart. Oral administration decreases dolichol, dolichyl-P and ubiquinone levels in heart and muscle, while in liver the dolichol level is elevated and ubiquinone level lowered. In brain the amount of dolichyl-P is increased. Intraperitoneal injection of mevinolin also modifies the liver dolichol and dolichyl-P isoprenoid pattern, with an increase in shorter chain polyisoprenes. The levels of dolichol and ubiquinone in the blood do not follow the changes observed in other tissues. Incorporation of [3H]acetate into cholesterol by liver slices prepared from mevinolin-treated rats exhibited an increase, whereas in brain no change was seen. Labeling of dolichol and ubiquinone was increased in both liver and brain, but incorporation into dolichyl phosphate remained relatively stable. The results indicate that mevinolin affects not only HMG-CoA reductase but, to some extent, also affects certain of the peripheral enzymes, resulting in considerable effects on the various mevalonate pathway lipids. PMID- 1420340 TI - Studies on the chemical structure of neutral glycosphingolipids in eggs of the sea hare, Aplysia juliana. AB - Six neutral glycosphingolipids (GL-1-GL-6) were obtained from eggs of the sea hare (Aplysia juliana) and were characterized by FABMS, 1H-NMR, partial acid hydrolysis, methylation studies and GC analysis of the component sugars, fatty acids and long-chain bases. The following structures were determined to be Glc beta 1-1Cer (89%) and Gal beta 1-1Cer (11%) for GL-1, Glc beta 1-1Cer (47%) and Gal beta 1-1Cer (53%) for GL-2 having hydroxy fatty acids in the ceramide moiety, Gal beta 1-4Glc beta 1-1Cer for GL-3, Fuc alpha 1-2Gal beta 1-4Glc beta 1-1Cer for GL-4, Gal alpha 1-2Gal beta 1-4Glc beta 1-1Cer for GL-5 and GalNAc alpha 1 3(Gal alpha 1-2)Gal beta 1-4Glc beta 1-1Cer for GL-6. The fatty acid composition of each glycosphingolipid, except for GL-2, which contained 2-hydroxypalmitic acid, consisted of mostly saturated C16-C20 acids, especially palmitic acid and stearic acid. The long-chain bases of all glycosphingolipids consisted mainly of branched nonadeca-4-sphingenine and octadeca-4-sphingenine. GL-6, which was one of the major glycosphingolipids, may be a precursor of a series of phosphonoglycosphingolipids which have been isolated from the skin of A. kurodai. PMID- 1420342 TI - Homology-derived three-dimensional structure prediction of Candida cylindracea lipase. AB - We propose a structural model of Candida cylindracea lipase (CCL) based on the reported X-ray structure of the highly homologous Geotrichum candidum lipase (GCL). The network of interactions around the active site, the salt and disulfide bridge pattern is conserved in the proposed structure. Functional, structural and evolutionary aspects of the peculiar usage of CTG codons by C. cylindracea ATCC 14830 are discussed. PMID- 1420341 TI - Differential effect of subspecies of lipoprotein containing apolipoprotein A-I on cholesterol efflux from cholesterol-loaded macrophages: functional correlation with lecithin: cholesterol acyltransferase. AB - Two species of lipoprotein containing apoA-I, one containing only apoA-I (LpA-I), and the other containing apoA-I and apoA-II (LpA-I/A-II), were tested for their effects on macrophage foam cells. Rat macrophages were converted to foam cells by incubation with radiolabeled acetylated LDL. Incubation with LpA-I or LpA-I/A-II decreased the cellular cholesteryl esters (CE) mass. However, the free cholesterol (FC) mass was only reduced by LpA-I. All the radioactivity excreted into the medium was associated with LpA-I or LpA-I/A-II; 39% of the excreted radioactivity was esterified in LpA-I and 10% in LpA-I/A-II. Upon complete inactivation of lecithin: cholesterol acyltransferase (LCAT) activity with dithiobisnitrobenzoic acid, the cholesterol reducing capacity of LpA-I was weakened significantly. However, the CE mass reducing capacity of LpA-I/A-II was not affected. When LpA-I and LpA-I/A-II were combined, the cholesterol reducing capacity of the mixture was similar to that of LpA-I alone. However, LpA-I re isolated from the medium showed a lower esterification rate than did the re isolated LpA-I/A-II, thereby indicating that the cholesterol esterified in LpA-I was transferred to LpA-I/A-II. These results suggest that (i) the function of LpA I is closely linked to the LCAT activity while that of LpA-I/A-II is not, and (ii) LpA-I in concert with LpA-I/A-II induces a series of extracellular events; LCAT-mediated esterification of excreted FC by LpA-I and a subsequent CE transfer to LpA-I/A-II. These mechanisms might be important for net cholesterol efflux from macrophage foam cells in physiological states. PMID- 1420343 TI - Enhancement of platelet functions by low density lipoproteins. AB - Platelet suspensions, that secreted about 50% of their dense granule contents upon stimulation with alpha-thrombin, showed a dose-dependent increase in secretion after 30 min preincubation with 0.5-3.0 g low density lipoprotein (LDL) protein/1. A 1-5 min preincubation had no effect. The enhancement by LDL only occurred at about 20% secretion or more, indicating that a minimal degree of activation was required for LDL to become effective. Lysine-modified LDL was equally effective as native LDL. The effect of LDL on secretion was accompanied by enhanced thromboxane B2 formation caused by stimulation of the liberation of arachidonate from phosphatidylcholine and/or phosphatidylinositol. However, when thromboxane formation was inhibited or the prostaglandin H2-thromboxane A2 receptor was blocked, LDL remained a potent stimulator of the secretion response. Thus, LDL enhances platelet secretion by a thromboxane A2-dependent and a thromboxane A2-independent mechanism via an effect that is independent of specific binding sites on the platelet. PMID- 1420344 TI - Activation of phospholipases in platelets by polyclonal antibodies against a surface membrane protein. AB - In a previous paper we demonstrated using immunochemical techniques that propolypeptide of von Willebrand factor was present on the surface of resting platelets. In the present paper we show that polyclonal antibodies against propolypeptide of von Willebrand factor induce activation of phospholipase(s) in platelets and lead to platelet aggregation. The antibody-stimulation of platelets induced the synthesis of thromboxane A2 (TXA2). Furthermore, the aggregation was inhibited by aspirin and an antagonist of TXA2. Aspirin inhibited not only the aggregation but also the activation of arachidonic acid liberation from phospholipids, but the effect of aspirin on arachidonic acid liberation was cancelled by the combined effect of the antibodies and a TXA2 mimetic agonist, which itself did not activate arachidonic acid liberation. The antibody-induced activation of arachidonic acid liberation and the aggregation were blocked by cytochalasin B. All these results obtained with antibodies were quite similar to the results obtained with collagen. PMID- 1420345 TI - Changes of membrane phospholipid composition of human erythrocytes in hyperlipidemias. I. Increased phosphatidylcholine and reduced sphingomyelin in patients with elevated levels of triacylglycerol-rich lipoproteins. AB - The composition of red blood cell membrane and plasma phospholipids has been analyzed in patients with hyperlipidemias. In red cells of patients with elevated levels of triacylglycerol-rich lipoproteins, phosphatidylcholine (PC) was raised and sphingomyelin (SM) reduced, resulting in a 20% increase of the membrane PC/SM ratio. In plasma phospholipids of these patients PC and SM levels were also higher and lower, respectively and the plasma PC/SM ratio was elevated by more than 50%. Close positive correlations between plasma and membrane phospholipids were obtained for PC, SM and the PC/SM ratio in normolipidemic and hyperlipidemic donors. Plasmalogen phosphatidylethanolamine (PE), a supposed endogenous protector against lipid oxidation, was reduced by about 20% in red cell membrane lipids in hyperlipidemic patients. Also plasmalogen-PE in plasma tended to be reduced in hyperlipidemic donors. Plasma HDL levels were positively related to the content of plasmalogen PE in the red cell membrane. In conclusion, there are closely related increases in PC/SM ratios in plasma and the red cell membrane in patients with elevated levels of triacylglycerol-rich lipoproteins. It is speculated that decreases in red cell membrane plasmalogen-PE in hyperlipidemic patients could be related to impaired antioxidant protection, possibly as a consequence of reductions in plasma HDL levels. PMID- 1420346 TI - Changes of membrane phospholipid composition of human erythrocytes in hyperlipidemias. II. Increases in distinct molecular species of phosphatidylethanolamine and phosphatidylcholine containing arachidonic acid. AB - The molecular species composition of red blood cell diacyl-phosphatidylcholine (PC), diacyl-phosphatidylethanolamine (PE) and alkenylacyl-PE (plasmalogen PE) has been analyzed in normolipidemic and hyperlipidemic donors. In all three phospholipid subclasses the percentages of the species 16:0/20:4 were increased in hyperlipidemic patients. In diacyl-PE, 18:1/20:4 was also elevated. No changes were observed in the other quantitatively important molecular species containing arachidonic acid at sn-2, namely 18:0/20:4. The rise in 16:0/20:4 in diacyl-PC and diacyl-PE of hyperlipidemic donors was accompanied by a fall in molecular species with linoleic acid (18:2) at sn-2 (in particular 18:1/18:2). In alkenylacyl-PE the elevation of 16:0/20:4 was compensated by a decrease in species with docosatetraenoic acid (22:4) at sn-2 in particular by a fall in 16:0/22:4. Among all donors, the percentages of 16:0/20:4 in diacyl-PC and PE were positively associated with plasma total cholesterol levels. The changes in molecular species composition of PC and PE in hyperlipidemia are expected to alter the function of erythrocyte membrane transport proteins and--if present also in other cell types--to affect eicosanoid metabolism. PMID- 1420347 TI - Synthesis, characterization and some properties of dideoxynucleoside analogs of cytidine diphosphate diacylglycerol. AB - Phospholipid conjugates of antiretroviral nucleoside analogs have been proposed to have several advantageous features when compared to the parent drugs (Hostetler, K.Y. et al. (1990) J. Biol. Chem. 265, 6112-6117). Here we report on the synthesis of one such type of lipid conjugates, i.e., nucleosides diphosphate diacylglycerols. The syntheses of 3'-azido-3'-deoxythymidine diphosphate diacylglycerol, 3'-deoxythymidine diphosphate diacylglycerol and 2',3' dideoxycytidine diphosphate diacylglycerol (with different acyl chains) were performed starting from phosphatidic acid and the antiviral nucleoside. A high performance liquid chromatography procedure for a single step purification of the compounds is presented. The compounds were characterized biochemically, using rat liver enzymes and chemically by phosphorus, fatty acid, ultraviolet, IR and 1H NMR analyses. Preliminary data on the behaviour in aqueous solution of some of the compounds are presented. PMID- 1420348 TI - A new glycolipid from Mycobacterium avium--Mycobacterium intracellulare complex. AB - From a nonpolar lipid fraction of Mycobacterium avium--Mycobacterium intracellulare complex cell mass, a new glycolipid was obtained, which was shown to be 5-mycoloyl-beta-arabinofuranosyl-(1-->2)-5-mycoloyl-alpha-ar abinofuranosyl (1-->1')-glycerol. When examined by TLC, all the 12 strains of this species tested, including clinical isolates, were found to contain this glycolipid. But the glycolipid was not detected in Mycobacterium bovis BCG or Mycobacterium tubrculosis H37Rv. PMID- 1420349 TI - Identification and characterization of apolipoprotein(AII-E2-AII) complex in human plasma lipoprotein. AB - A new apolipoprotein complex designated as the apo(AII-E2-AII) complex was identified in the lipoprotein fractions of human plasma with apoE phenotypes containing apoE2 (E4/E2, E3/E2, and E2/E2). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by an immunoblotting assay using anti apoE or anti-apoAII antibodies, established that the apo(AII-E2-AII) complex, with a molecular weight of 58,000, was identical to the complex consisting of apoE and apoAII, and that it also dissociated following reduction with beta mercaptoethanol. This new complex was also demonstrated to be distinct from the apo(E-AII) complex and apoE monomer by isoelectric focusing, in the samples that were not treated with beta-mercaptoethanol. In apoE phenotype E3/E2, the apo(AII E2-AII) complex was primarily included in the high-density lipoprotein (HDL, 1.063 < d < 1.21 g/ml) fraction, but was also observed in a small quantity in the very-low-density lipoprotein (VLDL, d < 1.006 g/ml) fraction. For further characterization, the apo(AII-E2-AII) complex was isolated by preparative SDS PAGE, and no contamination of apo(E-AII) complex and apoE monomer was detected by immunoblotting assay using an anti-apoE antibody. It was confirmed by an enzyme linked immunosorbent assay (ELISA) system that a molecular ratio between apoAII monomer and apoE in the isolated apo(AII-E2-AII) complex was approx. 2, when the apo(E-AII) complex was used as a standard with the ratio of 1:1. It indicates that the apo(AII-E2-AII) complex is formed from two molecules of apoAII monomer and one molecule of apoE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420350 TI - Protein transfer between A-I-containing lipoprotein subpopulations: evidence of non-transferable A-I in particles with A-II. AB - Transfer of apolipoproteins (apo) between the two subpopulations of apo A-I containing lipoproteins in human plasma: those with A-II [Lp(AI w AII)] and those without [Lp(AI w/o AII)], were studied by observing the transfer of 125I-apo from a radiolabeled subpopulation to an unlabeled subpopulation in vitro. When Lp(AI w AII) was directly radioiodinated, 50.3 +/- 7.4 and 19.5 +/- 7.7% (n = 6) of the total radioactivity was associated with A-I and A-II, respectively. In radioiodinated Lp(AI w/o AII), 71.5 +/- 6.8% (n = 6) of the total radioactivity was A-I-associated. Time-course studies showed that, while some radiolabeled proteins transferred from one population of HDL particles to another within minutes, at least several hours were necessary for transfer to approach equilibrium. Incubation of the subpopulations at equal A-I mass resulted in the transfer of 51.8 +/- 5.0% (n = 4) of total radioactivity from [125I]Lp(AI w/o AII) to Lp(AI w AII) at 37 degrees C in 24 h. The specific activity (S.A.) of A-I in the two subpopulations after incubation was nearly identical. Under similar incubation conditions, only 13.4 +/- 4.6% (n = 4) of total radioactivity was transferred from [125I]Lp(AI w AII) to Lp(AI w/o AII). The S.A. of A-I after incubation was 2-fold higher in particles with A-II than in particles without A II. These phenomena were also observed with iodinated high-density lipoproteins (HDL) isolated by ultracentrifugation and subsequently subfractionated by immunoaffinity chromatography. However, when Lp(AI w AII) radiolabeled by in vitro exchange with free [125I]A-I was incubated with unlabeled Lp(AI w/o AII), the S.A. of A-I in particles with and without A-II differed by only 18% after incubation. These data are consistent with the following: (1) in both populations of HDL particles, some radiolabeled proteins transferred rapidly (minutes or less), while others transferred slowly (hours); (2) when Lp(AI w AII) and Lp(AI w/o AII) were directly iodinated, all labeled A-I in particles without A-II were transferable, but some labeled AI in particles with A-II were not; (3) when Lp(AI w AII) were labeled by in vitro exchange with [125I]A-I, considerably more labeled A-I were transferable. These observations suggest the presence of non transferable A-I in Lp(AI w AII). PMID- 1420351 TI - Mevinolin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, suppresses enterocyte esterification of exogenous but not endogenous cholesterol. AB - Mevinolin (lovastatin), a competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase, directly inhibited acyl-CoA cholesteryl acyltransferase in rabbit intestinal microsomes at a dose of 20 micrograms/ml or more. Lineweaver-Burk analysis showed a competitive type of inhibition with respect to oleoyl-CoA. In cultured intestinal Caco-2 cells, mevinolin reduced [14C]oleate incorporation into cholesteryl-esters by 86% of controls at doses as low as 0.1 micrograms/ml. However, in cells whose activity of acyl-CoA cholesteryl acyltransferase was stimulated 7-fold by 10 mM mevalonolactone, a significant inhibitory effect on cholesteryl-ester formation could not be detected, even at 40 micrograms/ml of mevinolin. In contrast, cells supplied with liposomal cholesterol or cholesterol derived from low-density lipoproteins showed a marked reduction of cholesteryl ester formation in the presence of 10 or 0.1 micrograms/ml of mevinolin, respectively. It is concluded that the observed suppressive effects of mevinolin on cholesterol esterification in cultured Caco-2 cells are indirect and possibly caused by changes in the acyl-CoA cholesteryl acyltransferase substrate pool or intracellular cholesterol transport. PMID- 1420352 TI - Regulation of intestinal apo A-IV mRNA abundance in rat pups during fasting and refeeding. AB - The amount of intestinal apolipoprotein (apo) A-IV mRNA was examined in rat pups during fasting and refeeding. When 14-day old pups were fasted for 15 h, apo A-IV mRNA levels in the whole intestine decreased to 20% of the prefasting level. Refeeding casein and lactose, and the artificial milk composed of Intralipid, casein and lactose, caused an elevation of the apo A-IV mRNA after 3 h, without accompanying an elevation of serum triacylglycerols and apo A-IV (fat-independent elevation of apo A-IV mRNA). Refeeding Intralipid alone simultaneously elevated the apo A-IV mRNA, and serum triacylglycerols and apo A-IV after 3 h (fat dependent elevation of apo A-IV mRNA). Administration of physiological saline during fasting partly suppressed the reduction of the apo A-IV mRNA (40% of the prefasting level), and the dietary fat-independent elevation of the message disappeared. Refeeding dam's milk to the pups, fasted without water administration, increased the apo A-IV mRNA after 3 and 15 h, although the elevation of serum triacylglycerols and apo A-IV occurred only after 15 h. Refeeding the milk increased the apo A-IV mRNA after 3 h and 15 h. Refeeding dam's milk to the pups fasted with saline administration accelerated the fat dependent elevation of the apo A-IV mRNA. Simultaneously refeeding Intralipid and Pluronic L-81, an inhibitor of lymphatic fat transport, delayed the elevation of the apo A-IV mRNA and serum triacylglycerols and apo A-IV. Transcription rates of the apo A-IV mRNA, determined by nuclear run/on assay, were similar before and after fasting and refeeding Intralipid. During fasting, administration of puromycin, as compared with actinomycin D, enhanced the disappearance rate of the apo A-IV message. Intestinal mRNA for apo B, but not for apo A-I and beta-actin, similarly changed to the apo A-IV message. Thus, it can be concluded that: (1) dietary fat-dependent and -independent factors are involved in the elevation of the intestinal apo A-IV message; (2) the elevation of the message is not mediated by lipid uptake in the enterocytes but rather stimulated by the events leading to secretion of chylomicrons; and, (3) dietary fat-dependent elevation of the message appears to be due to the stabilization of the message. PMID- 1420353 TI - Characterization of recombinant human and rat pancreatic phospholipases A2 secreted from Saccharomyces cerevisiae: difference in proteolytic processing. AB - An expression plasmid for human pancreatic phospholipase A2 in Saccharomyces cerevisiae was constructed by insertion of cDNA encoding its preprophospholipase A2 into a yeast expression vector pAM82. The resulting product secreted in the yeast culture medium was mainly prophospholipase A2, which was the same as the natural proenzyme in all aspects examined, including the higher order structure. However, when the rat preprophospholipase A2 cDNA was manipulated in the same manner, the active phospholipase A2 of the intact mature form was secreted with the proenzyme being hardly detected in the medium. This unexpected favorable result would occur due to cleavage of rat phospholipase A2 pro-peptide by a trypsin-like proteinase in S. cerevisiae. Based on this finding, we constructed a plasmid carrying the sequence coding for the prepro-peptide of rat pancreatic phospholipase A2 behind the PHO5 promoter in the pAM82 vector, which leads to the secretion of heterologous proteins as their mature form. The use of this plasmid led to secretion of biologically active human pancreatic secretory trypsin inhibitor and a glutamic acid-specific endopeptidase from Staphylococcus aureus ATCC 12600, which are eukaryote and prokaryote proteins, respectively, in the culture medium of S. cerevisiae. PMID- 1420354 TI - Molecular cloning and sequence analysis of guinea-pig NADPH-cytochrome P-450 oxidoreductase [corrected]. AB - A cDNA clone coding for cytochrome P-450 oxidoreductase was isolated from a guinea-pig liver cDNA library. The cDNA, MSr2, contained a complete coding region of 678 amino acids. The amino acid sequence of the guinea-pig cytochrome P-450 oxidoreductase showed approx. 90% identities with those of rat, human, rabbit, pig enzymes indicating conservation of primary structure of the enzyme during evolutionary divergence of species. The high conservation of acidic residues of the enzyme sustained the importance of them to maintain its function [corrected]. PMID- 1420355 TI - Nucleotide sequence of hamster spermidine/spermine-N1-acetyltransferase cDNA. AB - The nucleotide sequence of a cDNA encoding hamster spermidine/spermine-N1 acetyltransferase, a key enzyme in polyamine degradation and excretion, has been determined. The cDNA consists of a 1016 base pair insert including 120 nucleotides of the 5' untranslated region and the complete 3' untranslated region. The deduced amino acid sequence is very similar to the human spermidine/spermine-N1-acetyltransferase with only 8 differences in 171 amino acids and the corresponding nucleotide sequence shows 91% identity. The 5' untranslated regions are even more closely related with 97% identity suggesting that this region may play a role in the regulation of acetyltransferase activity. Translation of the acetyltransferase mRNA in a reticulocyte lysate was not altered by the addition of N1,N12-bis(ethyl)spermine. PMID- 1420356 TI - Nucleotide sequence of the 5' end including the initiation codon of cDNA for the E1 alpha subunit of the human branched chain alpha-ketoacid dehydrogenase complex. AB - The 5' end including the start AUG codon has been defined for the human E1 alpha subunit of the branched chain alpha-ketoacid dehydrogenase complex by rapid amplification of cDNA ends. Considering conservative substitutions the amino acid sequence in the mitochondrial targeting sequence for the human clone is 73% identical to this sequence in rat and 84% identical to the bovine sequence. This peptide also shows similarity to the targeting sequence for the human beta subunit but not with targeting sequence for the other subunits of the complex. PMID- 1420357 TI - Somatic hypermutagenesis in immunoglobulin genes. II. Influence of neighbouring base sequences on mutagenesis. AB - A new approach for the analysis of hotspots of mutations is described. It is based on the classification of hotspot site sequences. Using this approach, the consensuses RGYW and TAA of hotspot sites were revealed in the V gene. Correlation between somatic mutations and these consensuses is investigated by the statistical weight method in 323 somatic substitutions in 14 V genes. Assuming the absence of any correlation, the probability of observing such data in the sample would be very low (0.0003). These results support the idea that emergence of somatic mutation is significantly influenced by neighbouring base sequences. This idea was also supported by the analysis of 296 somatic mutations in flanking sequences of V genes. It is supposed that this influence is an important feature of somatic hypermutagenesis. PMID- 1420358 TI - Cloning and characterization of the secY gene from the cyanobacterium Synechococcus PCC7942. AB - The secY gene product is an essential component of the Escherichia coli cytoplasmic membrane, which mediates the protein translocation across the membrane. We found a gene homologous to secY in the genome of the cyanobacterium Synechococcus PCC7942. The deduced amino acid sequence, 439 amino acids long, shows 43% homology with that of the E. coli secY. The hydrophobic profile suggests that the Synechococcus SecY protein is an integral membrane protein containing ten membrane-spanning segments, which are closely related to the E. coli counterpart. The SecY protein may participate in the protein translocation across the cytoplasmic or thylakoid membrane in Synechococcus PCC7942. PMID- 1420359 TI - Cloning and nucleotide sequence of the cDNA encoding human erythrocyte-specific AMP deaminase. AB - The nucleotide sequence of cDNA encoding human erythrocyte AMP deaminase has been determined by screening of human spleen cDNA library and by utilizing polymerase chain reaction (PCR) techniques. The 3.7 kb cDNA contains an open reading frame of 2301 bp which encodes 767 amino acids chain resulting in 89 kDa protein. The polyadenylation consensus signal (5'-AATAAA) located at 1212 bp 3' downstream from the stop codon. The homologies to human and rat muscle-specific AMP deaminases showed 64.1% and 65.2% identities, respectively, at the nucleotide level in the area of open reading frame, and 60.2% and 59.8% similarities at the deduced amino acid level. PMID- 1420360 TI - rel, NFKB, and the Brachyury T gene. AB - Comparing the sequences of the murine Brachyury T gene protein with the NKFB, rel and dorsal protein family reveals weak sequence similarities, including a DNA binding/dimerization motif. These similarities may reflect homologies between these proteins or may only be of phylogenetic relevance. PMID- 1420361 TI - Gender related differences in the expression and characteristics of glutathione S transferases of human colon. AB - In the present study, the expression of glutathione S-transferase (GST) isozymes was compared in human male and female colon tissues. GST isozymes were purified and quantified in five male and five female colon tissue samples. Noticeable differences were observed in the isoelectric focusing profiles (IEF) of the GSTs, from male and female colon tissues. Both male and female colon tissues had three common GST peaks with pI values of 9.2, 6.7 and 4.8. An additional GST peak with a pI value of 6.2 found in all females was not found in males. Based on kinetic, immunological and structural properties, these isozymes were classified into alpha (pI 9.2), mu (pI 6.7 and 6.2) and pi (pI 4.8) classes. Activity of the alpha-class GST in male colon was approx. 2-fold higher than the corresponding isozyme in female colon. The pi-class GST 4.8 was the most predominant GST in both the sexes and its activity with CDNB as substrate was more abundant (about 1.6-fold) in female colon as compared to that in male colon. Significant differences were seen in substrate specificities between male and female colon GST 4.8. Sex related differences were also observed in the inhibition kinetics of GST pi from male and female colon in the presence of hematin. In addition, GST pi isolated from female colon was more thermostable as compared to the corresponding male isozyme. The thermostability of purified GST pi isozyme from males or females was not affected by incubation of the enzyme with either estrogen, testosterone or progesterone. PMID- 1420362 TI - Stress factors affecting expression of O6-methylguanine-DNA methyltransferase mRNA in rat hepatoma cells. AB - O6-Methylguanine-DNA methyltransferase (MGMT) is decisively involved in protecting mammalian cells against genotoxic effects of alkylating carcinogens. We analysed regulation of MGMT expression after exposing rat hepatoma H4IIE cells to various 'stress' factors. Treatments that damage DNA such as alkylation, hydrogen peroxide, ultraviolet or X-ray exposure, as well as restriction enzymes introduced into cells by electroporation or arrest of replication by hydroxyurea significantly induced MGMT mRNA (2.5 to 5-fold). Slight induction (up to 2.5 fold) was observed after heat shock or cadmium/zinc treatment. No or only a very weak induction (less than 1.5-fold) was observed after treatment with 6 thioguanine, 5-azacytidine, transfection of methylated DNA, depletion of MGMT by feeding with O6-methylguanine or O6-benzylguanine, serum starvation and feeding of starved cells, cAMP, TPA and dexamethasone treatment. Inhibitors of protein kinases, H8 and H9, induced MGMT mRNA. On the other hand, an inhibitor of phosphatases (sodium vanadate) prevented induction of MGMT by N-methyl-N'-nitro-N nitrosoguanidine. The data indicate that DNA breaks are an ultimate signal for MGMT mRNA induction and that protein phosphorylation is involved in regulating MGMT expression. PMID- 1420363 TI - Involvement of AP1 and PEA3 binding sites in the regulation of murine tissue inhibitor of metalloproteinases-1 (TIMP-1) transcription. AB - Transcription of tissue inhibitor of metalloproteinases-1 (TIMP-1), a secreted protein that regulates the activities of the metalloproteinases, collagenase and stromelysin, is activated by serum growth factors. Transient transfection experiments have revealed several regions of cis-acting regulatory sequences involved in the response of the murine TIMP-1 gene to serum. One area is in the vicinity of the promoter, consisting of a non-consensus binding site (5'-TGAGTAA 3' at -59/-53) for transcription factor AP1 and an adjacent 24 bp region of dyad symmetry that contains a PEA3-binding site. A second is an upstream region (-1020 to -780) that acts as an enhancer when linked to a heterologous promoter, and contains a consensus AP1 binding site (at -803/ -797). Gel retardation assays revealed differences between nuclear factors in mouse C3H10T1/2 cells that bound to the TIMP(-59/ -53)AP1 site and a consensus collagenase TRE (TPA-response element). The TIMP(-59/ -53)AP1 site is a promiscuous motif that binds c-Fos/c Jun AP1 translated in vitro and is an effective competitor for binding of nuclear AP1 factors to the consensus TRE, but in addition it binds factors that do not associate with the consensus TRE. The TIMP(-59/ -53)AP1 motif and the dyad symmetry region stimulated expression from a thymidine kinase promoter in an additive fashion, and competition experiments showed that excess copies of these factor binding sites reduced expression from a reporter plasmid driven by the TIMP-1 promoter. Our data show that binding sites for AP1 and PEA3 transcription factors are involved in the regulation of TIMP-1 transcription, which suggests that the coordinated induction of TIMP-1, collagenase and stromelysin may be achieved through the actions of a shared set of nuclear transcription factors. However, the properties of the TIMP-1(-59/ -53)AP1 motif likely reflect an additional type of transcriptional regulation restricted to TIMP-1. PMID- 1420364 TI - Interaction of human and Escherichia coli tRNA(Phe) with human 80S ribosomes in the presence of oligo- and polyuridylate templates. AB - Human placenta and Escherichia coli Phe-tRNA(Phe) and N-AcPhe-tRNA(Phe) binding to human placenta 80S ribosomes was studied at 13 mM Mg2+ and 20 degrees C in the presence of poly(U), (pU)6 or without a template. Binding properties of both tRNA species were studied. Poly(U)-programmed 80S ribosomes were able to bind charged tRNA at A and P sites simultaneously under saturating conditions resulting in effective dipeptide formation in the case of Phe-tRNA(Phe). Affinities of both forms of tRNA(Phe) to the P site were similar (about 1 x 10(7) M-1) and exceeded those to the A site. Affinity of the deacylated tRNA(Phe) to the P site was much higher (association constant > 10(10) M-1). Binding at the E site (introduced into the 80S ribosome by its 60S subunit) was specific for deacylated tRNA(Phe). The association constant of this tRNA to the E site when A and P sites were preoccupied with N-AcPhe-tRNA(Phe) was estimated as (1.7 +/- 0.1) x 10(6) M-1. In the presence of (pU)6, charged tRNA(Phe) bound loosely at the A and P sites, and the transpeptidation level exceeded the binding level due to the exchange with free tRNA from solution. Affinities of aminoacyl-tRNA to the A and P sites in the presence of (pU)6 seem to be the same and much lower than those in the case of poly(U). Without a messenger, binding of the charged tRNA(Phe) to 80S ribosomes was undetectable, although an effective transpeptidation was observed suggesting a very labile binding of the tRNA simultaneously at the A and P sites. PMID- 1420365 TI - The unique structure of the Paramecium caudatum hemoglobin gene: the presence of one intron in the middle of the coding region. AB - The gene encoding hemoglobin (Hb) in the ciliated protist, Paramecium caudatum, has been cloned and sequenced. A single Hb locus was detected on an isolated genomic fragment with a size of approx. 15 kbp. This gene contained 443 bp. The 5' transcriptional regulatory region contained TATA box- and CAAT box-like sequences which resemble the structure of the promoter region in higher eukaryotic genes. The amino acid sequence deduced from the gene agreed precisely with that of the major Hb component. It was an unusual structure, much smaller than Hbs from many other organisms. Furthermore, all of the untranslated regions in this gene were also small. Particularly, one intervening sequence (intron) being only 23 bp was shorter than any other introns reported for eukaryotic genes encoding protein. The position of the intron in the P. caudatum Hb gene corresponded closely to that of the second intron which had been reported only for plant Hb genes. Possible routes for the evolution of Hb genes were discussed. PMID- 1420366 TI - Cloning of the cDNA for U1 small nuclear ribonucleoprotein particle 70K protein from Arabidopsis thaliana. AB - We cloned and sequenced a plant cDNA that encodes U1 small nuclear ribonucleoprotein (snRNP) 70K protein. The plant U1 snRNP 70K protein cDNA is not full length and lacks the coding region for 68 amino acids in the amino-terminal region as compared to human U1 snRNP 70K protein. Comparison of the deduced amino acid sequence of the plant U1 snRNP 70K protein with the amino acid sequence of animal and yeast U1 snRNP 70K protein showed a high degree of homology. The plant U1 snRNP 70K protein is more closely related to the human counter part than to the yeast 70K protein. The carboxy-terminal half is less well conserved but, like the vertebrate 70K proteins, is rich in charged amino acids. Northern analysis with the RNA isolated from different parts of the plant indicates that the snRNP 70K gene is expressed in all of the parts tested. Southern blotting of genomic DNA using the cDNA indicates that the U1 snRNP 70K protein is coded by a single gene. PMID- 1420367 TI - Cloning of the C alpha catalytic subunit of the bovine cAMP-dependent protein kinase. AB - The bovine C alpha type catalytic subunit of the cAMP-dependent protein kinase was cloned. A partial cDNA was isolated from a bovine heart cDNA library. This clone contained 120 bp of the coding sequence and the entire 3' untranslated region of 1431 bp. The complete coding region was cloned by PCR amplification from total bovine heart and skeletal muscle RNA. The sequence of the 3' oligonucleotide was taken from the partial cDNA clone whereas the 5' oligonucleotide was chosen by comparison of sequences of published C alpha subunits from other species. In the deduced amino acid sequence there is one deviation from the published bovine C alpha protein sequence, aspartic acid 286 is exchanged by an asparagine. The C alpha mRNA was found to be expressed differentially in various bovine tissues. PMID- 1420368 TI - The two splice variants of collagen XII share a common 5' end. AB - The short splice variant of collagen XII is composed of 1960 amino acid residues. This polypeptide contains the same signal peptide and the same carboxy-terminus as the long splice variant, but lacks an internal fragment of 1164 amino acid residues. Thus, the two variants of collagen XII are not created by the use of two different transcription initiation sites as generally assumed, but result from the inclusion or skipping of several exons located within the collagen XII gene. PMID- 1420370 TI - Linkage position determination in a novel set of permethylated neutral trisaccharides by collisional-induced dissociation and tandem mass spectrometry. AB - A set of neutral permethylated trisaccharides identical in the non-reducing (A--- B) disaccharide and linkage isomeric in the reducing terminal (B----C) disaccharide has been synthesized. Collision-activated tandem mass spectrometry was used for analysis of the B----C linkage position. The trisaccharides, gal(beta 1----4)glc(beta 1----X)glc, where X = 3, 4 and 6, were synthesized and examined using fast atom bombardment collision-induced dissociation tandem mass spectrometry. Results were rationalized using molecular modeling. We have previously reported results for determination of the A----B linkage position with isomeric sets of synthetic trisaccharides containing internal amino sugars. The neutral trisaccharides were synthesized to isolate electronic effects of the amino group. An approach of relating daughter ion to parent ion ratios and collision energy offset was used to generate slopes that predict linkage position in glc beta 1----X glc reducing end glycoside form of terminal trisaccharides. PMID- 1420369 TI - Nucleotide sequence of rat erythropoietin. AB - The cDNA for the rat erythropoietin (EPO) has been cloned and sequenced. The deduced amino acid sequence consists of 166 amino acid residues, which has a 79% and 95% homology with human and mouse EPOs, respectively. Many short stretches, highly conserved in primate and rodent EPOs, are found in the 3'-noncoding region when insertions and deletions are taken into consideration. PMID- 1420371 TI - Measurement of muscle protein fractional synthetic rate by capillary gas chromatography/combustion isotope ratio mass spectrometry. AB - The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12C. The purpose of this study was to compare muscle (13C)leucine enrichment measured with the conventional preparative GC/ninhydrin IRMS approach to a new, continuous-flow technique using capillary GC/combustion IRMS. Quadriceps muscles were removed from four Sprague-Dawley rats after each was infused at a different rate with (1-13C)leucine for 6-8 h. Muscle leucine enrichment (at. % excess) measured by both methods differed by less than 4%, except at low (13C)leucine enrichments (less than 0.03 at. % excess). In addition, capillary GC/combustion IRMS was used to assess muscle (13C)leucine enrichment and fractional muscle protein synthesis rate in ten normal young men and women infused with (1,2-13C2)leucine for 12-14 h. This approach reduced the variability of the isotope abundance measure and gave estimates of muscle protein synthesis rate (0.050 +/- 0.011% h-1 (mean +/- SEM); range = 0.023-0.147% h-1) that agree with published values determined using the standard analytical approach. The measurement of (13C)leucine enrichment from skeletal muscle protein by capillary GC/combustion IRMS provides a simple, acceptable and practical alternative to preparative GC/ninhydrin IRMS. PMID- 1420372 TI - Liquid chromatographic/atmospheric pressure chemical ionization mass spectrometric analysis of synthetic elastase inhibitor peptide. AB - A liquid chromatographic/atmospheric pressure chemical ionization mass spectrometric method for the determination of tert-butyloxycarbonyl-Tyr-Leu-Val CH2Cl (Boc-YLV-CH2Cl) was investigated. Boc-YLV-CH2Cl was eluted from a Cosmosil 5C8 column in a solvent system of 0.1% acetic acid-methanol (30: 70, v/v). The positive ion spectrum of Boc-YLV-CH2Cl showed a quasi-molecular ion at m/z 526 with fragment ions which provided structural information. Boc-YLV-CH2Cl was purified from blood and tissue samples with Sep-Pak C18 cartridges. The analysis in biological samples was performed by focusing the characteristic ion at m/z 526. The calibration graphs were linear over the concentration range studied (injected amounts of 9.5-190 pmol). The method was applied to the determination of Boc-YLV-CH2Cl in biological samples. PMID- 1420373 TI - Mass spectrometric quantification of cysteine-containing leukotrienes in rat bile using 13C-labeled internal standards. AB - Leukotriene C4 and N-acetyl leukotriene E4 were determined in rat bile using a procedure based on high-performance liquid chromatographic fractionation, hydrogenation to 5-hydroxyeicosanoic acid, and gas chromatographic/mass spectrometric selected ion monitoring analysis of the pentafluorobenzyl ester, trimethylsilyl ether derivatives. 13C4-Labeled analogs of the leukotrienes were synthesized and used as internal standards. The concentrations of both leukotrienes in rat bile were markedly elevated after administration of endotoxin to anesthetized animals; N-acetyl leukotriene E4 was the more abundant product. The presence of leukotriene C4 in rat bile after endotoxin challenge was confirmed by fast atom bombardment/tandem mass spectrometry with precursor ion scanning. Quantitative determination of leukotriene C4 using the tandem mass spectrometric procedure was consistent with the gas chromatographic/mass spectrometric data but the latter procedure gave a substantially lower detection limit. PMID- 1420374 TI - Design and optimization of a micropump-based electrospray device for preparation of nitrocellulose substrates for plasma desorption time-of-flight mass spectrometry. AB - Details of a nitrocellulose (NC) substrate preparation technique in 252Cf plasma desorption time-of-flight mass spectrometry were investigated using an electrospray device, in which a micropump was employed for solution delivery. The molecular ion yields for three standard proteins (porcine insulin, chicken-egg lysozyme and chymotrypsinogen A) were studied as a function of the electrosprayed NC layer thickness, spray rate, NC solution concentration and some other parameters. Optimal parameters of the NC substrate preparation procedure were determined, which include deposition of a layer of 250-750 micrograms cm-2 at up to 15 microliters min-1 spray rate and up to 15 micrograms microliters-1 solution concentration. PMID- 1420375 TI - Determination of L-654,066, a new 5 alpha-reductase inhibitor in plasma by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry. AB - L-654,066 is a new 5 alpha-reductase inhibitor. A sensitive and specific assay based on combined liquid chromatography/mass spectrometry has been developed for the determination of this drug candidate in plasma. The analyte was isolated from plasma by solid-phase extraction on a C-18 cartridge. A related substance, L 683,838, was used as the internal standard. Extracts were chromatographed on a 5 cm C18 reverse-phase high-performance liquid chromatography column interfaced via the heated nebulizer probe to a corona discharge chemical ionization source. The mass spectrometer was operated in the positive ion tandem mode. The method has sufficient sensitivity, precision, accuracy and selectivity for the analysis of clinical samples containing L-654,066 at concentrations in the range 0.5-20 ng ml 1. The chromatographic run time is less than 2 min. PMID- 1420376 TI - Simultaneous determination of tenidap and its stable isotope analog in serum by high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry. AB - A specific high-performance liquid chromatographic/atmospheric pressure chemical ionization tandem mass spectrometric assay for the quantitative determination of tenidap and its D3 analog in human serum is described. The assay exhibited a linear dynamic range of 0.1-25 micrograms ml-1. Its precision for the two analytes over the range was 17% or better. The assay validity and its utility to investigate changes in tenidap bioequivalence and pharmacokinetics are presented. PMID- 1420377 TI - Water as a useful calibrant for thermospray mass spectrometry. AB - The present report demonstrates that thermospray liquid chromotography/mass spectrometry (LC/MS) calibration can be easily achieved by the observation of water cluster ions in filament-on or discharge ionization modes. Cluster ions of sizes ranging from 1 to 44 water molecules are readily observed and thus are useful over the mass range from 17 to 792 Da. PMID- 1420378 TI - Hybrid tandem mass spectrometers in biological research. PMID- 1420379 TI - Optimization of short-column gas chromatography/electron ionization mass spectrometry conditions for the determination of underivatized anabolic steroids. AB - A gas chromatographic/mass spectrometric method based on the use of short capillary gas chromatograph columns (3-5 m) and electron ionization mass spectrometry has been optimized and evaluated for the determination of underivatized anabolic steroids. The short-column gas chromatographic/mass spectrometric method was shown to result in short analysis times and to require minimal sample preparation, but suffered from some loss in sensitivity and chromatographic resolution compared with conventional gas chromatographic/mass spectrometric techniques for derivatized steroids. Therefore, short-column gas chromatographic conditions were optimized to maximize the sample transfer efficiency (sensitivity) from the gas chromatograph into the ion source of the mass spectrometer, while maintaining chromatographic integrity and minimizing thermal decomposition. Mass spectrometric conditions were optimized to maximize ionization efficiency with respect to the intensity of the molecular ion and degree of fragmentation such that positive identification of each steroid could be made based on the resulting mass spectra. Under optimized conditions, we have shown that underivatized anabolic steroids spiked into urine samples can be determined at low-nanogram levels using short-column chromatography/full-scan electron ionization mass spectrometry. PMID- 1420380 TI - Utility of liquid chromatography/fast atom bombardment mass spectrometry and liquid chromatography/thermospray mass spectrometry for structure identification of metabolites of a fluorinated herbicide. AB - This study demonstrates a useful application of on-line microbore high performance liquid chromatography (HPLC) fast atom bombardment (FAB) and thermospray (TSP) mass spectrometry techniques for identification of metabolites from the in vitro metabolism of an experimental Monsanto herbicide: 2-chloro-N (ethoxymethyl-N-[2-methyl-6- (trifluoromethyl)phenyl]acetamide, 'chloroacetanilide'. The microbore HPLC FAB technique on a high-resolution sector mass spectrometer accelerated identification of polar metabolites from the in vitro metabolism study of the herbicide. It provided good chromatographic resolution and excellent FAB sensitivity with strong protonated molecular ions. Scanning high-resolution LC/FAB mass spectrometry also provided molecular formulae for structural elucidation of unknown metabolites. Sample purification and concentration were minimized. Identification of less polar metabolites was carried out using LC/TSP mass spectrometry with a quadrupole mass spectrometer. LC/TSP mass spectrometry provided useful structural information for both polar and less polar metabolites because their spectra showed more fragmentation than FAB spectra. Glutathione conjugation was the major reaction observed during in vitro incubation of the herbicide. Oxidation of the chloroacetanilide by rat liver enzymes was also a significant metabolic reaction. Seven metabolites were identified, of which four were glutathione conjugates. PMID- 1420381 TI - Fast atom bombardment and tandem mass spectrometry at high and low collision energy for the sequence analysis of low to middle-mass peptides. PMID- 1420382 TI - Electron impact and fast atom bombardment mass spectrometric analysis of the food borne carcinogens 2-amino-3-methylimidazo [4,5-f] quinoline, 2-amino-3,8 dimethylimidazo [4,5-f] quinoxaline and their metabolites. AB - Electron impact (EI) and fast atom bombardment (FAB) mass spectrometry were used to characterize the heterocyclic aromatic amines, 2-amino-3-methylimidazo[4,5 f]quinoline and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and their metabolites. The carcinogenic N2-hydroxy metabolites and several non-conjugated detoxification products were analysed directly by EI mass spectrometry, while several polar sulphate and beta-glucuronic acid conjugates were analysed by FAB mass spectrometry. Analysis of beta-glucuronic acid conjugates was also achieved by EI mass spectrometry following silylation. PMID- 1420383 TI - [Radioimmunoscintigraphy: fundamentals (1)]. AB - Radioimmunoscintigraphy (scintigraphy of benign and malignant diseases with radioactively labelled monoclonal antibodies) is being performed via clinically controlled studies in Germany since 1985. In this review the immunological fundamentals and diagnostic possibilities of this new diagnostic approach are given described. PMID- 1420385 TI - [A debatable issue: indications for the selection and use of absorber materials]. AB - In response to the present occasion, the areas of application of different radiation-absorbent test device materials used in practice are presented in an overview. The test methods recommended for acceptance and constancy testing, the absorbers suitable for this as well as the dependence of a few test parameters relevant to image quality and their tolerances regarding the absorber material are described. The test results are verified and it is shown that in the use of technical test devices, unusually high dose tolerances or high densities of the test device exposures, for example, are by all means in agreement with good technically induced medical imaging quality. PMID- 1420386 TI - [Magnetic resonance angiography: physical principles and clinical applications]. AB - Within the last four years magnetic resonance angiography (MRA) developed very rapidly towards a well accepted screening technique for vascular examinations as a fast add on to conventional MR. This review describes the basic physical principles as well as the different methods like time-of-flight and phase sensitive MRA for visualization of blood vessels. Different applications of 3D, 2D sequential and 3D multi-volume MRA are shown from various regions of the head and body. A short outlook to quantitative flow measurements is given in the last chapter including some interesting applications of these techniques which show the still expanding potential of magnetic resonance. PMID- 1420384 TI - [Radioimmunoscintigraphy of colorectal tumors: state of the art (2)]. AB - Radioimmunoscintigraphy (RIS) of colorectal carcinomas is under investigation in controlled clinical studies in Germany since 1985. With the availability of 99mTc labelled monoclonal antibodies against the carcinoembryonic antigen (CEA), there is an increasing acceptance of this new technique; nevertheless, the merits of RIS in comparison to established methods of staging and restaging of patients with colorectal carcinomas as computed tomography, endoscopy and sonography are still under discussion. In this review the current "State of the Art" of radioimmunoscintigraphy of colorectal carcinomas is given in respect of whether there is additional information which can be gained only by Ris but not by the established diagnostic procedure. PMID- 1420388 TI - [The importance of CT for the diagnosis of adrenal gland tumors: myelolipoma]. AB - Myelolipoma is a rare benign tumour of the adrenal cortex. 20% of the patients have intratumoral, mostly tiny foci of calcifications. In most cases CT, as the gold standard for imaging the adrenal gland, is able to diagnose the myelolipoma. MR yields no additional information. Even large tumours with or without calcifications can remain without surgical intervention if there is a regular follow-up. The indications for surgical management are reduced by the characteristic appearance of this tumour on CT scan. PMID- 1420387 TI - ["Pseudo-dissection" in an abdominal aortic aneurysm]. AB - Sonography of 52 patients with aneurysms of the abdominal aorta revealed in 7 cases hypoechoic crescent-like zone between parietal thrombus and the aortic wall which simulated aortic dissection. Duplex-sonography was performed in all cases and no flow could be detected in this area. In two patients intraoperatively several milliliters of a serous fluid could be aspirated from this zone which confirmed the suggestion of seroma within the parietal thrombus. This observation may be found rather frequently and should not be a reason for immediate surgery. PMID- 1420389 TI - [Complications in the kidney pelvis and the ureter following kidney transplantation]. AB - Development of complications of the pelvis and the ureter, especially obstruction and necrosis with an urinary fistula was seen in 35 of 751 patients after kidney transplantation (4.6%). In this study they occurred significantly often in patients with multiple renal arteries of the donor kidney, for example pole arteries. An arterial angiography of the aorta abdominalis in living donors before transplantation is not be neglected. The diagnosis of urological complications includes sonography, in cases of ureteral obstruction percutaneous antegrade urography, and in a given case computed tomography. PMID- 1420390 TI - [Bladder tumors--Magnevist-assisted magnetic resonance tomography]. AB - Magnetic resonance imaging (MRI, Magnetom 0.5 Tesla) using a high-resolution surface coil was performed on 10 healthy volunteers, 16 patients with bladder tumours, 2 patients with cystitis and 15 patients with bladder tumours and cystitis. Lesion delineation versus urine, bladder wall and surrounding organs was evaluated in plain and contrast-enhanced (IV Magnevist, 0.1 mmol/kg) T1 weighted, plain proton-density and T2-weighted spin-echo images. Surface-coil MRI proved very sensitive since all lesions were found in plain scans. Cystitis and 27 of 31 tumours exhibited contrast enhancement, however, differentiation of tumours and cystic lesions was not improved. Plain T2 and contrast-enhanced T1 weighted images demonstrated bladder wall disruption and perivesical tumour spread with equal sensitivity. Post-contrast images permitted unequivocal visualisation of perivesical tumour spread in surrounding peritoneal fat. The authors conclude that T2-weighted imaging may be restricted to non-enhancing bladder tumours thus significantly reducing imaging time. PMID- 1420391 TI - [The clinical relevance of sonography in intensive care units]. AB - 336 sonographic examinations were performed with a portable ultrasound scanner on 217 patients in intensive-care units. In 302/336 (90%) cases, the region of clinical interest could be demonstrated completely or mostly by ultrasound. The clinical question could be answered by ultrasound in 270/310 (87%) cases partially. In 17/210 (5%) cases the clinical question could not be answered by ultrasound, in 26/336 (8%) cases there was no clinical question at all. 211/336 (63%) sonographic examinations were retrospectively classified as clinically relevant. A large part of clinically relevant examinations was found at the sonographic evaluation of the liver (100%), of the pericardium (96%), of the kidneys (89%), of the blood vessels (80%), of the gallbladder (78%), of the pleural space (76%) and on sonographic evaluation of patients with blunt abdominal trauma (91%). A relatively small part of clinically relevant examinations was found at sonographic evaluation of circumscribed or free intraabdominal fluid (59% resp. 57%), of cholestasis (53%) and of suspected neoplasm (11%). Sonographic examinations of the pancreas (40%) or the spleen (33%) and examinations without any clinical question (50%) also showed little clinical relevance. PMID- 1420392 TI - [Bladder outflow obstruction due to a small, median prostatic cyst--diagnosis and interventional radiology treatment]. AB - We describe a rare case of a bladder outlet obstruction due to a midline prostatic cyst. In the following clinical appearance, diagnostic imaging and therapy by CT-guided punction are reported. Differential diagnosis and therapy are discussed. PMID- 1420393 TI - [Detection of a pheochromocytoma in the urinary bladder wall]. AB - We present the case of a 23-year old female patient with clinical signs and biochemical results of a pheochromocytoma. Abdominal ultrasound gave no hints on localisation. Angiography demonstrated a richly vasculated tumour in the region of the superior urinary bladder. Computed tomography (CT) was able to localise the tumour but could not differentiate the tumour origin in bladder or uterus. The selective venous catheter blood sampling confirmed the localisation of the norepinephrine producing pheochromocytoma in the inferior pelvic region. Intraoperative diagnosis turned out to be an extra-adrenal pheochromocytoma of unknown tumour status in the dorsal bladder wall. PMID- 1420394 TI - A national survey of physicians' and nurses' attitudes toward endoscope cleaning and the potential for cross-infection. AB - To elicit information on endoscope cleaning practices and the perceived risk of cross-infection, questionnaires were mailed to 500 physicians and 1,000 gastroenterology nurses and associates in November and December 1991. The survey results indicated that while the majority (83% of nurse/associates and 82% of physicians) expressed satisfaction with current cleaning methods, levels of confidence in endoscope reprocessing varied in several key areas. Concern about the potential for device-borne human immunodeficiency virus transmission was expressed by 82% of nurses and 87% of physicians, while 75% of nurses and 53% of physicians feared being liable should cross-infection occur. While most respondents (86% of physicians and 30% of nurses) were unaware of cross-infection incidents, 6% of nurses reported outbreaks in their institutions. According to survey responses, the risk of cross-infection may be attributable to variable cleaning practices--failure to clean scopes before placing them in disinfectant, abbreviated overall cleaning times, and inconsistent disinfectant immersion times -that may be compounded by unreliable automatic disinfectors. At least once a year endoscopes were blocked by debris according to 74% of nurses and 72% of physicians. Reactions to glutaraldehyde had been experienced by 87% of nurses and 65% of physicians. Gastroenterology professionals may be unaware of the actual incidence of cross-infection, but recognize its potential. Lapses in cleaning practices and the difficulty in monitoring postendoscopy nosocomial infections add to their uncertainty. PMID- 1420395 TI - Celiac disease--a patient's perspective. PMID- 1420397 TI - Endoscopic retrograde hemorrhoidal sclerotherapy. AB - This article describes an endoscopic retrograde hemorrhoidal sclerotherapy technique that is well tolerated and associated with high patient satisfaction, low complication rates, and satisfactory long-term results. This therapy is best used when colonoscopy is performed, and the need for treatment of hemorrhoidal disease is identified prior to the procedure. Since conventional sclerotherapy equipment is used, the demands on the endoscopy staff and finances are lessened. This article also discusses the implications for nursing care and patient teaching associated with this procedure. PMID- 1420396 TI - Primary biliary cirrhosis: current diagnosis and treatment. AB - Primary biliary cirrhosis is a progressive noninflammatory destruction of the interlobular bile ducts within the liver, leading to cholestasis and eventual cirrhosis. Ninety percent of affected patients are women. Most patients are initially without symptoms or have mild symptoms such as fatigue or pruritus. A minority of patients have the classical triad of jaundice, pruritus, and xanthelasmas. Almost all patients will have positive anti-mitochondrial antibody test results and an elevation of the serum alkaline phosphatase level. Primary biliary cirrhosis is thought to be an autoimmune disorder with additional liver injury being mediated by the subsequent cholestasis and accumulation of toxic bile acids. New treatment modalities include colchicine, ursodeoxycholic acid, and methotrexate. All patients, including those with only minor symptoms, have increased mortality compared with age-matched controls, thereby emphasizing the need for early diagnosis. PMID- 1420398 TI - Droperidol (Inapsine). AB - Droperidol may be used to bring about conscious sedation in therapeutic and diagnostic endoscopy. Droperidol is a neuroleptic tranquilizer that produces marked tranquilization and sedation. Droperidol may be used to allay apprehension and provide a state of mental detachment while maintaining reflex alterness necessary in endoscopic interventions. Adverse reactions to droperidol are generally self-limiting or readily managed with hydration to correct hypotension. PMID- 1420399 TI - Quality review in the endoscopy setting. PMID- 1420400 TI - Going home with a percutaneous endoscopic gastrostomy: a reference for patients and care givers. PMID- 1420401 TI - Growth hormone treatment for the elderly? PMID- 1420402 TI - Age-related modifications in neural cardiovascular control. AB - Integrated cardiovascular responses to a range of different stimuli, as well as the overall, spontaneously occurring variability in blood pressure and heart rate, undergo complex changes with aging. A general trend is that homeostatic control mechanisms lose part of their ability to modulate heart rate and to buffer the concomitant blood pressure variations; the two phenomena are possibly linked by a cause-effect relationship. A detailed analysis of the age-related changes in the major reflex systems reveals a clear-cut impairment in arterial baroreceptor control of the heart rate, but much less pronounced changes in its control of blood pressure, on the other hand, both the hemodynamic and humoral components of the cardiopulmonary reflex appear to be markedly attenuated. The experimental evidence of the mechanisms underlying these changes is still largely incomplete, and it appears that the gaps will have to be filled by a systematic, detailed analysis, i.e., that no generalizations or extrapolations will be possible. Indeed, the data available so far indicate that the age-related alterations are highly non-uniform, some functions undergoing a definite impairment but others being much better preserved and some being even enhanced; thus aging is by no means associated with a generalized decline in cardiovascular functions and should instead be viewed as a complex, highly selective process. These peculiar biological features of the aging phenomena merit further investigation in both the cardiovascular and the other organ systems, in order to verify the possibility that currently unrecognized homeostatic potentials in the elderly subject may be exploited to advance his/her clinical management in health and disease. PMID- 1420403 TI - Stress, glucocorticoids, and aging. AB - Attention has long been focused on the relationship between stress and aging, both under the guise of stress as an accelerator of normal aging and of aging as a time of impaired ability to cope with stress. This review examines the considerable amount of evidence in support of these views. We address these ideas with respect to glucocorticoids, the adrenal steroid hormones secreted during stress. In particular, we concentrate on three model systems: 1) programmed senescence in marsupial mice and semelparous fish as mediated by glucocorticoid excess; 2) glucocorticoid hypersecretion in rats and its role in damaging the aging brain; and 3) potential human and primate adrenocortical dysfunction during aging. We discuss physical and cognitive consequences of adrenocortical dysfunction in these systems, and how they may relate to human aging. PMID- 1420405 TI - Changes in posture and balance with age. AB - Changes in posture with age are of concern because of their association with impaired mobility and the possibility of falls. In this study alignment of the joint centers and balance of body segments were measured in 41 women, aged 65 and older, and correlated with weight, age, change in height, and activity. Balance was assessed by calculating the whole-body center of gravity, and the partial centers of gravity above the knee and hip. Compared to a younger reference population, the older subjects had greater kyphosis, a more posterior hip position, and leaned forward more from the hips (more anterior center of gravity above the hips). Among the 41 elderly subjects, larger kyphoses correlated with greater decrease in height. Elderly subjects who were inactive tended to learn more, but forward lean was not correlated to other variables. These findings suggest two separate sets of changes: an osteoporosis-related stooping, and also a forward lean that may relate to muscular weakness or to fear of instability. Posture among the elderly was quite varied and did not follow any one pattern of change. PMID- 1420404 TI - Age-related changes in tissue contents of immunoreactive calcitonin gene-related peptide. AB - Age-related changes in calcitonin gene-related peptide (CGRP) content were found in a number of rat tissues, and most can be explained by the physiological and pathological changes associated with advancing age. In some specific areas of the brain, and some cardiovascular tissues such as atria and arteries, the CGRP content declined with age (p < 0.01), while the contents were increased in the thyroid gland, plasma and in veins (p < 0.01). In the substantia nigra and striatum, the immunoreactive-CGRP (i-CGRP) levels found in older rats were about 50% of those found in adolescent rats (p < 0.01). The i-CGRP levels found in the penis, bladder, kidney, testis and adrenal gland gradually increased up to maturity, and then rapidly declined in the aging rats. However, in the lungs and sensory ganglia (dorsal root and trigeminal), the highest content of i-CGRP was found in immature 3-week-old rats, and then declined with age. Changes of i-CGRP observed with age may support multiple physiological roles for CGRP at various stages of development. The changes described here, particularly in the lungs, substantia nigra, striatum and the cardiovascular system, should help in further understanding the physiological and pathophysiological role of CGRP in health and in age-related disorders. PMID- 1420406 TI - Norepinephrine sensitivity of the endocrine pancreas in aging F344 rats. AB - The effect of norepinephrine (NE) infusion on glucose-stimulated insulin secretion was evaluated in whole perfused pancreases isolated from 6-, 12-, and 26-month-old male Fischer 344 (F344) rats. Glucose-stimulated insulin secretion was significantly inhibited by NE in all age groups. There was no significant effect of aging on the sensitivity or magnitude of inhibition at any of the concentrations of NE. In contrast, vascular pressure attained during NE infusion was significantly less in the 26-month-old rats compared to 6- and 12-month-old animals. These results suggest that the adrenoceptor neuroeffector mechanism of the smooth muscle declines at a faster age-related rate than does the beta-cell's adrenoceptor mechanism. PMID- 1420407 TI - Effect of cholinergic tone on growth hormone-releasing hormone-induced secretion of growth hormone in normal aging. AB - Aging is associated with an impairment in the GH response to GHRH and to several other stimuli of GH secretion. We evaluated the effect of pyridostigmine (PD) or placebo pretreatment (Protocol A: placebo or 120 mg PD orally at 8 a.m.; Protocol B: placebo or 60 mg PD twice orally at 9 p.m. and 7 a.m.) on GH responsiveness to GHRH (1 micrograms/kg BW bolus i.v. at 9 a.m.) in 15 normal elderly males (65-92 years) and in 14 normal young adults (20-37 years). GH response to GHRH was significantly reduced in elderly subjects compared to young adults (p < 0.05). PD (Protocol A) increased GH release in both elderly and young subjects. In elderly men, PD enhanced GH response to GHRH. The phenomenon was more evident when PD was administered according to Protocol B (p < 0.01). The area under the curve of GH was significantly greater after PD plus GHRH than it was after placebo plus GHRH (p < 0.01). In young adults, PD induced an increase in GH responsiveness to GHRH when administered according to Protocol A (p < 0.05) but not Protocol B. Both GH peak and AUC of GH after PD plus GHRH (Protocols A and B) in elderly subjects were not significantly different from the same parameters found in young subjects after placebo plus GHRH. Our data confirm that pituitary somatotrophin responsiveness to GHRH in man changes with aging. PD restores GH responsiveness to GHRH in elderly subjects. The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420408 TI - Clinical trials in cognitive impairment in the elderly. AB - The pharmacological treatment of dementia is particularly difficult because of the uncertainty of the diagnosis and of the underlying pathogenetic processes, and because of the variable severity of the syndrome. This paper suggests several lines for future therapeutic trials in dementia. These include the need to work with homogenous populations and to take into account the natural history of the disease, the pharmacologic characteristics of the drugs, and the particular ethical considerations pertaining to demented patients. We review the diagnostic criteria for dementia, Alzheimer's disease (AD) and vascular dementia. We discuss the different types of therapeutic trial design, the problem of the duration of the protocol, the tools to evaluate the cognitive effects and the activities of daily living, and the use of a Clinical Global Impression of Change (CGIC). The results of some therapeutic trials in AD and vascular dementia are given as examples. PMID- 1420409 TI - Conference on the physiologic basis of frailty. April 28, 1992, Baltimore, Maryland, U.S.A. Introduction. PMID- 1420410 TI - The role of DNA damage and its repair in the aging process. PMID- 1420411 TI - Relationship between the immune system and frailty: pathogenesis of immune deficiency in HIV infection and aging. PMID- 1420413 TI - Metabolic deterioration with advancing age: the role of physical activity. PMID- 1420412 TI - Growth hormone, IGF-I, gonadal steroids, and aging. PMID- 1420415 TI - Decline in neuromuscular function as an index of frailty: insights from studies in aging rodents. PMID- 1420414 TI - Malnutrition and chronic inflammation: causes or effects of frailty? PMID- 1420416 TI - [Unevenness of distribution of historical events throughout an 11-year solar cycle]. AB - Tchizhevsky hypothesis (1922) of historical process heliotaraxia (helios--sun, taracsio--perturb) was empirically tested. Samples of near 13 and 4.6 thousand events mentioned in Chronology sections of two largest Soviet historical handbooks were analyzed. Events were classified into 4 groups on the basis of "strength" and "social contradictions meaning" of their names, called tolerance and polarity: tolerant--intolerant (e.f. riot--roform) and polar--neutral (e.f. civil war-external war). It was found that frequency and polarity of historical events increased in maximum of sunspot cycle and in the next year as compared with minimum and the year before minimum. The probability of revolution (the most polar and intolerant name of historical event) is the highest in maximum and the lowest in the year before minimum. Intolerance of polar events increased and neutral events decreased in maximum. All these relations were highly significant (P < 0.001). It was concluded that heliotaraxic phenomena exist and are basically associated with year of sunspot maximum. PMID- 1420417 TI - [Sensitivity of biological objects to the effects of the geomagnetic field]. AB - It is shown on the basis of calculations of energy sublevels of the hyperfine structure that the effect of the geomagnetic field upon the impurity atoms in the volume of living cells should be considered in relation to the value of geomagnetic field induction pulses delta B. When delta B > or = 10 pT and the dielectric constant epsilon > or = 10, magnetodipole transitions between sublevels of the hyperfine structure within one term are possible in impurity atoms in their 2P-state. During magnetic storms with delta B > or = 100 nT magnetodipole or magnetoquadrupole forced transitions from 2P1/2 and 2P3/2 states to 2S1/2 metastable state are possible in the resonant zones formed by intersection of hyperfine energy sublevels of the corresponding excited levels. PMID- 1420418 TI - [Biological detector of weak cosmic fields]. AB - Possibility of use of biological object as a detector of faint cosmophysical fields is discussed. The signals of free induction and electric echo caused by a short-term effect of light with an intensity of approximately 0.2 mWt/sm2 on biological systems were observed. The experiments with Blatella germanica, Muska domestica were performed in vivo and with red and green seaweeds and yeast cells in vitro. The signals were detected by means of the dielectric permeability measurement in a dynamic regime. Main features of the observed responses are described and assumption on mechanisms of their origin are given. An example of registration of the Lunar eclipse on a detector with in active element of Blatella germanica is given. PMID- 1420419 TI - [Effect of fluctuations of solar activity of biological systems]. PMID- 1420420 TI - [The effect of weak variable extremely low frequency magnetic fields on the infra day rhythm of the rat sympathoadrenal system]. AB - It was found in open test that changing magnetic fields with 8 Hz frequency and 5 mcTl induction in daily 3 hours exposition on rats with a middle level of the mobile activity move the phase of diuresis daily rhythms and epinephrine and norepinephrine yield as well. In rats with desinchronosis provoked by hypokinesia the changing magnetic fields restore the synchronism of the studied processes. PMID- 1420421 TI - [Temporal analysis of calls of the psychiatric emergency medical aid team]. AB - 6075 calls for the psychiatric emergency ambulance unit were reviewed. An analysis of the hourly and 24-hour number of calls showed the existence of 24 hour, lunar and seasonal rhythms in the frequency of calls. The correlation between clinical symptoms and the number of calls points to aggravations of diseases. The accumulated data indicate that there is a connection between the dynamics of the psychopathological processes and ecological factors which are determined by periodic fluctuation of gravitation fields. PMID- 1420423 TI - [Cosmophysical correlations in live and non-live nature as a manifestation of weak interactions]. AB - Determination of weak effects is proposed, their relationship with cosmophysical correlations is advanced. The experimental results are presented on the intensification coefficient of weak effects (10(4)) for polarized electromagnetic radiation. The magnetoresonance mechanism of weak effects is suggested. The experimental evidence in favor of this mechanism and its application to the problems of cosmophysical correlations are given. PMID- 1420422 TI - [The synchronizing effect of infralow frequency magnetic fields on biological systems]. AB - Time-organization of lipid peroxidation and thiol groups exchange was examined. It was shown that one-divisible 3-hours effect of the extremely low magnetic fields depending on the frequency ensured formation of definite rhythm of the investigated processes. The obtained results are considered as an evidence of frequency-dependent adoption of the magnetic fields by the living systems according to the mechanism of forced synchronization of elementary cyclic processes underlain by integral oscillations. PMID- 1420424 TI - [Effect of an infralow frequency magnetic field on nerve cell rhythm and their resistance to hypoxia]. AB - The direct effect of infralow-frequency (0.05, 0.1, 0.25 Hz, 100 nT) magnetic fields (MF) was demonstrated on the brain cellular--tissue model--surviving slices of mouse cerebellum. MF influence is a trigger for the nervous cells. MF-5 Hz revealed two-phases response: inhibition and excitation of the impulse activity of neurons. Besides that we recorded convulsive effect of MF. The experiments with simultaneous exposure of hypoxia and MF revealed a prohypoxia effect of MF, when the oxygen concentration was very low and also after reoxygenation. The surviving slices may be used as a model for studying the fine mechanisms of influence of different intensity MF on the nervous cells. PMID- 1420425 TI - [Cosmophysical fluctuations and development of the human embryo]. AB - An analysis of the dependence of embryonic pathology development on heliocosmic factors is conducted and regular changes of the appearance of different kinds of pathology depending on heliocosmic situations in different months of the year are shown. Periods of conception of increasing amount of children with different disturbances of development coincide with values of the Wolf's number and sun radiation stream density of certain ranges in comparison with the mean values, the same indexes are in conformity with the periods of conception of children having haemolytic disease and diabetic foetopathy. PMID- 1420426 TI - [Geocosmic factors in adaptation of intracellular energetics in diseases of pregnant and confined women and children]. PMID- 1420427 TI - [Correlation of the probability of occurrence of breast neoplasms with solar activity]. AB - A contingent with high incidence of precancerous breast diseases (1080 persons) was studied to assess the relationship between solar activity and 1) alterations in the relationship between women with early menarche and women with middle and late menarche (high and low risk of breast cancer respectively) and 2) incidence of benign breast diseases. It was established that population content alterations were wave-like and had statistically significant periods 3,5; 7 and 12 years, and correlate with Wolf number changes. Incidence of benign breast diseases in the group aged 20-50 years also changed periodically (T = 11 years) depending on the birth-year and correlated conversely with Wolf numbers at the birth-years. Incidence of benign breast diseases changes periodically in the population of women with early menarche with the period of 3.6 years, and in those with middle and late menarche--with the periods of 10.5, 3.2 and 4 years. There is a statistically significant correlation between the incidence of benign breast diseases and Wolf numbers in population of women with middle and late menarche. PMID- 1420428 TI - [Connection between the sector structural of the interplanetary magnetic field and hematologic indicators in normal and neoplastic processes]. AB - Interplanetary magnetic field (IMF) sector polarity was compared to hematologic indexes of normal mice and mice after single injection of carcinogen 1,2 Dimethylhydrazine. It has been established that the hemoglobin level and the number of leucocytes in the standard blood volume depend on IMF sector polarity: both indexes are higher at +IMF, than at -IMF. Mice injected with carcinogen have mainly higher hemoglobin level at +IMF and mainly lower one at -IMF than the control mice. PMID- 1420429 TI - [Modulation of energy metabolism of lymphocytes in children by natural physical factors]. AB - The aim of this work is exploration of natural physical factors influencing change of age-dependent energy exchange parameters (e.g. activity of SDG) in healthy and premature children. 35 healthy and 35 premature children were investigated over 11 years from early antenatal and postnatal period. Cytochemical investigations were carried out 1-2 time a year until 6 years of age. Solar activity, geomagnetic excitability, air temperature and atmospheric pressure and its diurnal variation on index represented environmental factors. It is suggested that quiet magnetic field might be a predictor of higher level of SDG activity and vice versa. Higher activity of magnetic field leads to displacement of maximum-age of SDG activity to an earlier age. Lymphocytes react to magnetic storm in a phasic manner. Other physical environmental factors might have reciprocal effect so that some of them could negate the effect of others. If intrauterine development took place in a year of higher solar activity, early development results. However, later development is characterized by lower level of SDG activity. On premature children, as well as in healthy subjects, the more influencing factors on energetic age-dependent parameters are geomagnetic field and variation of atmospheric SDG activity in healthy children is within normal range (and has a training effect), while in premature children depression of hydrogenase in the end stage. PMID- 1420430 TI - [The possible effect of parameters of the gravitational field on indicators of functional asymmetry of the brain]. AB - Correlation of the brain functional asymmetry (BFA) in 2400 humans born in 1930 1984 and numbers of the joining of planets, moon and the Sun was investigated in corresponding years of conception and birth. A significant correlation with BFA was found in men, while there was no such correlation in women. PMID- 1420431 TI - [Deviation from a Poisson distribution in a series of identical tests of E. coli cultures as a result of the effect of correlating factors of exo- and endogenous natures]. AB - Vital cells number (VCN) in the sampling of E. coli populations was experimentally measured and distribution histograms were obtained. In most cases distributions show considerable deviation from Poisson model. VCN distribution histograms are polymodal, dispersion/arithmetical mean ratio may essentially differ from 1. The more essential differences from Poisson distribution were observed for populations with the higher cell concentration. Computer simulation of the VCN histograms indicated that additional parameters (such as those describing cellular interaction of different nature and/or other factors that influence random behaviour of cells) should be introduced into Poisson model to explain observed variations in VCN distribution histograms. PMID- 1420432 TI - [Reaction of rats with various constitutional features to the effect of weak variable magnetic fields of extremely low frequency]. AB - The influence of 8 Hz frequency and 5 mcTl induction changing magnetic fields on the functional state of blood neutrophils, sympathoadrenal system and brain integrative activity in rats with low, middle and high level of mobility was investigated in open test. It was found out that changing magnetic fields provoke the stress-reaction development in rats with low mobile activity. The adaptation which develops in rats with high and middle mobile activity comes later by 5-7 days in high mobility rats. PMID- 1420433 TI - [Processing biorhythmic data modified by a cosinor analysis method]. AB - Modified Cosinor-Analyses method used in processing of biorhythmological data is considered. Advantages of modified method and its practical results are shown. Assumption of oscillations with the periods of 4-6 hours in humans daily physiological activity is confirmed. PMID- 1420434 TI - [Natural and technogenic electromagnetic background and its effect on the environment]. AB - Causes of the initiation of natural and technogenic electromagnetic background, its effect on the man and environment are considered. Ideas are discussed of eliminating negative consequences of the effects of electromagnetic waves of different range on the man. PMID- 1420436 TI - A non-nucleotide-based linking method for the preparation of psoralen-derivatized methylphosphonate oligonucleotides. AB - A method is reported for conjugating an analog of 4'-(aminomethyl)-4,5',8- trimethylpsoralen to methylphophonate oligonucleotides. This method enables the psoralen moiety to be coupled to the phosphonate backbone between any two desired bases in a sequence. When hybridized to a target mRNA, the psoralen moiety can be directed toward a uridine base and, in turn, can undergo a photo-addition reaction with the target under UV irradiation at 365 nm. Several different non nucleotide-based amino-linker reagents have been prepared for incorporation into methylphosphonate oligonucleotides by standard phosphonamidite chemistry. In addition, an N-hydroxysuccinimide activated ester analog of 4'-[(3 carboxypropionamido)methyl]-4,5',8- trimethylpsoralen has been synthesized for conjugation to the amino-linker moieties. Using this approach, we have prepared a number of psoralen-methylphosphonate-oligonucleotide conjugates which are complementary to the chimeric bcr/abl mRNA associated with chronic myelogenous leukemia. Solution hybridization studies with a 440-base subfragment of the bcr/abl RNA have shown that the psoralen moiety does not adversely affect duplex stability. Polyacrylamide gel electrophoresis analyses have demonstrated that the psoralen-oligonucleotide conjugates undergo photo-addition to the RNA in a sequence-specific manner. Optimal photo-addition occurs when the psoralen moiety is inserted adjacent to one or more adenine residues in the oligonucleotide sequence, particularly between adenine and thymine (5'-3'). This internal labeling approach greatly increases the number of potential target sites available for photo-cross-linking experiments. PMID- 1420435 TI - Conjugates of anticancer agents and polymers: advantages of macromolecular therapeutics in vivo. PMID- 1420437 TI - Preparation and characterization of recombinant proricin containing an alternative protease-sensitive linker sequence. AB - The aim of this study was to determine the feasibility of utilizing a factor Xa specific cleavage site within a recombinant protein containing the ricin A chain (RTA) sequence. Release of RTA is believed to be an essential step during the intracellular phase of ricin intoxication. Failure to incorporate such cleavage sites in fusions containing RTA results in a loss of toxin action (O'Hare, M., et al. (1990) FEBS Lett. 273,200. Kim, J., and Weaver, R.F. (1988) Gene 68,315). In this report we describe the introduction of a factor Xa-specific site in the linker of proricin, which we use here as a model substrate. Upon purification of the recombinant mutant proricin after expression in Xenopus oocytes, we demonstrate that the protease does have access to the engineered recognition sequence (albeit at low efficiency) and that the presence of the latter does not interfere with disulfide bond formation or the lectin activity of the ricin B chain moiety. Upon cleavage and reduction, the RTA polypeptide displays ribosome inactivating ability, indicating that the presence of the modified linker at its C-terminus does not interfere with its catalytic activity. The general applicability of using such a cleavage site in recombinant fusions with RTA is discussed. PMID- 1420438 TI - A novel method for the incorporation of glycoprotein-derived oligosaccharides into neoglycopeptides. AB - We describe a new method for the transfer of carbohydrate moieties to polypeptides in which complex carbohydrate, in the form of glycosyl amino acid, is removed from an available glycoprotein, derivatized, and reacted with a polypeptide via an iodoacetylated alpha-amino group. A family of oligomannose chains, N-linked to the side chain of Asn, was obtained from ovalbumin by pronase digestion and purified as previously described. A reactive sulfhydryl group was specifically placed on these molecules by reaction of 2-iminothiolane with the Asn alpha-amino group. Separately, the alpha-amino group of the peptide GGYR was specifically iodoacetylated by reaction with iodoacetic anhydride at pH 6. Reaction of the thiol-containing carbohydrate with iodoacetylated peptide at pH 8 gave in high yield the corresponding oligomannosyl-peptides, whose structures were confirmed by mass spectrometry. A peptide inhibitor of HIV protease was also oligomannosylated by this procedure. The principle advantage of this method is the efficiency of the reaction even when performed with stoichiometric amounts of the two molecules at low concentration. It should be feasible to extend this chemistry to larger polypeptides. PMID- 1420440 TI - Synthesis and high stability of complementary complexes of N-(2 hydroxyethyl)phenazinium derivatives of oligonucleotides. AB - Two simple methods for the synthesis of oligonucleotides bearing a N-(2 hydroxyethyl)phenazinium (Phn) residue at the 5'- and/or 3'-terminal phosphate groups are proposed. By forming complexes between a dodecanucleotide d(pApApCpCpTpGpTpTpTpGpGpC), a heptanucleotide d(pCpCpApApApCpA), and Phn derivatives of the latter, it is shown that the introduction of a dye at the end of an oligonucleotide chain strongly stabilizes its complementary complexes. The Tmax and the thermodynamic parameters (delta H, delta S, delta G) of complex formation were determined. According to these data, coupling of a dye with the 5' terminal phosphate group is the most advantageous: delta G(37 degrees C) is increased by 3.59 +/- 0.04 kcal/mol compared to 2.06 +/- 0.04 kcal/mol for 3'-Phn derivatives. The elongation of the linker, which connects the dye to the oligonucleotide, from a dimethylene up to a heptamethylene usually leads to destabilization of the oligonucleotide complex. The complementary complex formed by the 3',5'-di-Phn derivative of the heptanucleotide was found to be the most stable among all duplexes investigated. Relative to the unmodified complex the increase in free energy was 4.96 +/- 0.04 kcal/mol. The association constant of this modified complex at 37 degrees C is 9.5 x 10(6) M-1, whereas the analogous value for the unmodified complex is only 3 x 10(3) M-1. PMID- 1420439 TI - A new method to specifically label thiophosphorylatable proteins with extrinsic probes. Labeling of serine-19 of the regulatory light chain of smooth muscle myosin. AB - We present a new method to specifically and stably label proteins by attaching extrinsic probes to amino acids that are thiophosphorylated by protein kinases and ATP gamma S. The method was demonstrated for labeling of a thiophosphorylatable serine of the isolated regulatory light chain of smooth muscle myosin. We stoichiometrically blocked the single thiol (Cys-108) either by forming a reversible intermolecular disulfide bond or by reacting with iodoacetic acid. The protein was stoichiometrically thiophosphorylated at Ser-19 by myosin light chain kinase and ATP gamma S. The nucleophilic sulfur of the protein phosphorothioate was coupled at pH 7.9 and 25 degrees C to the fluorescent haloacetate [3H]-5-[[2-[(iodoacetyl)-amino]ethyl]amino]naphthalene-1- sulfonic acid ([3H]IAEDANS) by displacement of the iodide. Typical labeling efficiencies were 70-100%. The labeling was specific for the thiophosphorylated Ser-19, as determined from the sequences of two labeled peptides isolated from a tryptic digest of the labeled protein. [3H]IAEDANS attached to the thiophosphorylated Ser 19 was stable at pH 3-10 at 25 degrees C, and to boiling in high concentrations of reductant. The labeled light chains were efficiently exchanged for unlabeled regulatory light chains of the whole myosin molecule. The resulting labeled myosin had normal ATPase activities in the absence of actin, indicating that the modification of Ser-19 and the exchange of the labeled light chain into myosin did not significantly disrupt the protein. The labeled myosin partially retained the elevated actin-activated Mg(2+)-ATPase activity which is characteristic of thiophosphorylated myosin. This indicates that labeling of the thiophosphate group with [3H]IAEDANS did not completely disrupt the functional properties of the thiophosphorylated protein in the presence of actin. PMID- 1420441 TI - A convenient and flexible approach for introducing linkers on bifunctional chelating agents. AB - The synthesis of a protected bifunctional analog of ethylenediaminetetraacetic acid (EDTA) is described. The molecule contains an aminobenzyl moiety that allows the easy attachment of the chelating agent to a wide variety of groups. Examples of reaction with the C-termini of two peptides are given. In the following paper, the two peptides are used to study the enzymatic cleavage of metal chelates from a monoclonal antibody. PMID- 1420443 TI - Preparation of 5- and 6-(aminomethyl)fluorescein. AB - 5(6)-Carboxyfluorescein is protected as the diacetate then reduced to 5(6) (hydroxymethyl)fluorescein diacetate. The separated isomers are subjected to a Mitsunobu reaction with dibenzyl imidodicarbonate, yielding diprotected 5- and 6 (aminomethyl)fluorescein diacetate. Methanolysis of the acetates followed by deprotection with HBr/acetic acid gives 5- and 6-(aminomethyl)fluorescein hydrobromide. PMID- 1420442 TI - Influence of a peptide linker on biodistribution and metabolism of antibody conjugated benzyl-EDTA. Comparison of enzymatic digestion in vitro and in vivo. AB - Insight into the metabolism of radiolabeled antibodies is important for the design of better radioimaging and therapy agents. To test the effect of linkers that can be cleaved in vivo, we introduced Ala-Leu-Ala-Leu between the antibody Lym-1 and an 111In-labeled benzyl-EDTA. For comparison, we studied a conjugate without the linker. Digestion of the two conjugates in vitro showed that the one with Ala-Leu-Ala-Leu was cleaved rapidly by the liver protease cathepsin B1 (T1/2 approximately 6 h). After 100 h of digestion, reversed-phase HPLC product analysis of the Ala-Leu-Ala-Leu conjugate showed that 48% of the total radioactivity had the same retention time as (p-aminobenzyl)-EDTA(In), and 37% of the total radioactivity had the same retention time as [p-(Ala-Leu-amido)benzyl] EDTA(In). After 97 h of digestion, the conjugate without the linker had 79% of the radioactivity activity still attached to the protein. We also tested the two conjugates in mice. Ala-Leu-Ala-Leu had only a moderate effect on the whole body and liver clearance in vivo. The excretion of the radioactivity was about 6% per day with the linker and about 3% per day without the linker. HPLC analysis of the urine of a single mouse showed products similar to the in vitro study; 54% of the excreted radioactivity had the same retention time as (p-aminobenzyl)-EDTA(In), while 10% had the retention time of [p-(Ala-Leu-amido)benzyl]-EDTA(In). PMID- 1420444 TI - Genetic lesions in preleukemia. AB - Preleukemia is thought to be a clonal disorder of hemopoietic stem cells. The conversion of a normal cell into a preleukemic and ultimately leukemic state is a multistep process requiring the accumulation of a number of genetic lesions. The myelodysplastic syndromes have become a paradigm for human preleukemia, where nonrandom chromosomal abnormalities, including complete or partial deletions of chromosomes five and seven, trisomy eight and Y chromosome loss suggest specific changes. Of particular significance are 5q deletions, as many genes important in hemopoiesis are located in this region, including the proto-oncogene FMS, which encodes the receptor for the macrophage colony-stimulating factor, CSF-1. Genetic damage such as point mutations in the RAS and FMS genes has been detected in preleukemia patients. The RAS gene family (N, K and H) encodes membrane-bound G proteins, which, like other proto-oncogenes, are components of the intracellular signal transduction pathways controlling mitogenesis and differentiation. The characterization of such lesions may ultimately identify those patients at greatest risk of leukemic transformation. PMID- 1420446 TI - The June RAC meeting. PMID- 1420445 TI - The ras/cholesterol connection: implications for ras oncogenicity. AB - The frequent detection of mutated ras genes in a variety of cancers (reviewed in Bos, 1988, 1989; Der, 1988) suggests that ras makes a significant contribution to human malignancies (reviewed in Barbacid, 1987; Lacal and Tronick, 1988; Der, 1989). While the role of ras in malignancy is unclear, it is well-established that the association of ras protein with the inner surface of the plasma membrane is critical for triggering ras oncogenicity. The trafficking of ras proteins to the plasma membrane requires a series of three closely linked posttranslational modifications (farnesylation, proteolysis, and carboxymethylation) that are signaled by the consensus C-terminal CAAX motif present on all ras proteins (reviewed in Rine and Kim, 1990; Gibbs, 1991; Der and Cox, 1991). THe recent discovery that an essential intermediate in cholesterol biosynthesis, the isoprenoid farnesol, is attached covalently to ras proteins has stimulated considerable interest and has identified important new directions for studies of ras function. First, understanding the role of farnesol-linked interactions with the plasma membrane may identify the biochemical basis for the oncogenic actions of ras proteins. Second, the enzymes that catalyze the processing steps that trigger membrane association of ras proteins are promising targets for pharmacologic intervention in ras-associated disease. In this review, we summarize our current knowledge of the role of posttranslational processing in ras-membrane interaction and transforming activity. We also provide an update of recent studies addressing the role of isoprenoid modification in the function of ras and of other isoprenoid-modified proteins (reviewed in James and Olson, 1990; Glomset et al., 1990; Maltese, 1990). While this role is likely to be specific for each protein, ras proteins can provide an excellent prototype for understanding the role of isoprenoid modification in protein function. PMID- 1420447 TI - A model for predicting the risk of cancer consequent to retroviral gene therapy. AB - Theoretical estimates of the risk of cancer resulting from accidental insertion of retroviral gene therapy vectors into oncogenically vulnerable genomic sites may prove an important supplement to experimentally derived data in estimating risk/benefit ratios for future gene therapy trials. We have approached risk assessment by considering either a single vector insertion event or a single natural mutation to be potentially oncogenic, should either occur in a cell that would otherwise end with one less than the total number of mutations required for frank neoplasia. Estimates of the relative probabilities of these two phenomena yield a relative risk assessment, which in conjunction with epidemiologic data on natural cancer frequencies can be converted into an assessment of absolute risk. This approach yields an estimated range of relative risk over 10 years of about 1.00000026 to 25 for cells bearing single copies of inserted vectors; the upper limit is higher for multiple copies. These estimates, if accurate, imply that small experimental human or animal gene therapy cohorts will rarely, if ever, manifest vector-related cancers and that more precise future risk assessments will require additional data on natural and vector-induced mutation rates. PMID- 1420448 TI - Transplantation of genetically modified autologous hepatocytes into nonhuman primates: feasibility and short-term toxicity. AB - Ex vivo gene therapy directed to the liver is being developed for the treatment of inherited metabolic diseases. Transplantation of hepatocytes that have been transduced with a low-density lipoprotein (LDL) receptor gene is a potential form of therapy for familial hypercholesterolemia (FH). We have demonstrated efficacy of ex vivo gene therapy for familial hypercholesterolemia in a rabbit animal model of this disease. In preparation for human trials, we describe in this report experiments in baboons for documentation of the feasibility and safety of autologous hepatocyte transplantation. Three baboons underwent a partial hepatectomy and their hepatocytes were isolated, cultured, and transduced with a retrovirus containing the human LDL receptor gene. The hepatocytes were harvested and infused into an indwelling catheter that had been placed into the inferior mesenteric vein at the time of liver resection. The baboons tolerated the procedures well and are being maintained and clinically evaluated for an indefinite time period. Follow-up evaluations have ranged from 3 to 8 months. Clinical evaluations have been unremarkable and blood chemistry and hematology determinations have stayed within normal limits. PMID- 1420449 TI - Public acceptance of human gene therapy and perceptions of human genetic manipulation. AB - Clinical trials of gene therapy are underway in different countries, and further countries can be expected to use gene therapy soon. Little remains known, however, about public perceptions of gene therapy. Nationwide mail response opinion surveys were conducted in Japan in August-October, 1991. A total of 54% of the public, 65% of the high school biology teachers, and 54% of the scientists who responded said that they would be willing to use gene therapy, and 66%, 73%, and 62%, respectively, said that they would be willing to use gene therapy on their children. There appears to be growing acceptance of gene therapy in Japan, although about one-quarter of the population are against it. The underlying reasoning behind the acceptability of human genetic manipulation and perceived benefits and risks are presented, and these were found to be generally similar to reasoning expressed in a similar survey conducted in New Zealand in May, 1990. Public perceptions are also compared to those in Europe and the United States. People perceive both benefits and risks from genetic manipulation. There appears to be more teaching of ethical, social, and environmental issues associated with genetic engineering in senior high school biology classes in New Zealand than in Japan. In Japan and New Zealand, about 90% of the public would support including discussion of social issues associated with science and technology in the curriculum. PMID- 1420450 TI - Report of the Committee on the Ethics of Gene Therapy. PMID- 1420451 TI - Genetics, Religion and Ethics Project. The Institute of Religion and Baylor College of Medicine, The Texas Medical Center, Houston, Texas, June 1, 1992. PMID- 1420452 TI - Treatment of patients with advanced cancer using tumor infiltrating lymphocytes transduced with the gene of resistance to neomycin. PMID- 1420453 TI - Clinical protocol of human gene transfer for hemophilia B. PMID- 1420454 TI - Treatment of patients with severe combined immunodeficiency due to adenosine deaminase (ADA) deficiency by autologous transplantation of genetically modified bone marrow cells. PMID- 1420455 TI - Immobilized proteins as chromatographic supports for chiral resolution. AB - This review examines the role of protein-bonded chiral stationary phases (CSPs) in enantiomeric separation and investigates the performance characteristics and desired properties of protein CSPs for separation and large-scale operation. The review also discusses the ability of protein-based CSPs to examine the stereochemistry of drug metabolism processes. PMID- 1420456 TI - The S-oxidative degradation of a novel corticosteroid tipredane (INN). Part I: Preliminary investigations into the hydrogen peroxide S-oxidation of tipredane. AB - The C-17 dithioketal moiety of the corticosteroid tipredane (INN, I) has been shown to undergo peroxide oxidation yielding an array of sulphoxide epimers. All epimers have been isolated and characterized by spectroscopic techniques. Oxidation of the C-17 beta methylthio-substituent appeared to occur exclusively giving a 4:1 ratio of the S:R configuration at the sulphoxide moiety. Both methylthiosulphoxide epimers (V) have been shown to be susceptible to thermolysis yielding the monoethylthio- derivative (VI) via elimination of methylsulphenic acid. As expected from stereochemical considerations at the C-17 position the S epimer has been found to be more susceptible than its corresponding R epimer towards thermolysis. The monomethylthiosulphoxide epimers (III) were produced in a 1:1 ratio, indicating that they were formed from the oxidation of the corresponding monomethylthio- derivative (VII). This probably arose from the elimination of ethylsulphenic acid from the alpha-ethylthiosulphoxide (VIII). PMID- 1420457 TI - Determination of gold-based antiarthritis drugs and their metabolites in urine by reversed-phase ion-pair chromatography with ICP-MS detection. AB - A sensitive method for the determination of gold-based drugs auranofin, myochrysine, and their metabolites has been developed. These gold-containing compounds were separated by reversed-phase ion-pair chromatography with tetrabutylammonium chloride as the ion-pairing agent. Gold-specific on-line detection utilized inductively coupled plasma mass spectrometry (ICP-MS). The separation conditions of pH, methanol content, concentration of the ion-pairing agent and ionic strength have been investigated. The detection limit for auranofin, the last peak in the chromatogram, was 0.3 ng. These methods were applied to the analysis of gold-containing species in urine from arthritis patients on auranofin, myochrysine or solganol therapy. The recovery of the total gold-containing species from urine was greater than 90%. Dicyanogold(I) anion, [Au(CN)2]-, was detected in the urine of several patients. PMID- 1420458 TI - Direct injection analysis of carbamazepine and its active 10,11-epoxide metabolite in plasma by use of a semipermeable surface (SPS) silica column in LC. AB - A semipermeable surface (SPS) silica column was applied for the simultaneous determination of carbamazepine (CBZ) and its active 10,11-epoxide metabolite (EPO) in plasma following direct injection in LC. The SPS packing material consists of an ODS ligand as the hydrophobic inner phase and a polyoxyethylene network as the hydrophilic outer phase. When a 5-microliters portion of intact plasma was injected onto the column using a mobile phase of phosphate buffer (pH 7.1, ionic strength 0.1)-acetonitrile (4:1, v/v), the plasma proteins were size excluded, whereas the drug and its metabolite were retained and separated both from each other and from other commonly co-administered drugs such as phenobarbital (PB) and phenytoin (DPH). The calibration graphs (peak area vs concentration) of CBZ, EPO and PB were linear over the therapeutic range of plasma concentration (r greater than 0.998) with good relative standard deviations (RSD less than 3.98%, n = 5). The recoveries from plasma were almost complete (greater than 96.6%). The analysis time was 17 min. The method as developed was applied in studies on the time course of plasma concentrations of unchanged CBZ and EPO after i.v. administration of CBZ to the rat. PMID- 1420459 TI - Analysis of [14C]-saterinone and its metabolites in dog plasma, urine and bile by high-performance liquid chromatography with radioactivity and fluorescence detection and by mass spectrometry. AB - An HPLC method was developed for the direct on-line radioactivity determination of [14C]-saterinone and its metabolites in biological canine fluids after intravenous and intraduodenal administration. After direct injection of 200 microliters of sample, the metabolites were separated on a semi-preparative reverse-phase column. The metabolites were identified by HPLC reference standards, enzymatic hydrolysis and mass spectrometry. Besides a small amount of unchanged saterinone, six metabolites could be detected, both in bile and urine. The main fraction (about 80-90% of the sum of detected metabolites) contained the phase II metabolites of saterinone, the sulphate and glucuronide. Ring hydroxylated saterinone and three metabolites that were not identified made up about 1-4% each. In plasma, only the major compounds could be detected because of the lower absolute concentrations. The metabolic pathway of saterinone in dogs was elucidated and compared with other species. Results from previous studies concerning a first-pass metabolism could be confirmed. PMID- 1420460 TI - Synthesis and spectroscopic studies of norethylmorphine. PMID- 1420461 TI - Analysis and pharmacokinetics of a new prodrug N-l-leucyldoxorubicin and its metabolites in plasma using HPLC with fluorescence detection. PMID- 1420462 TI - Rapid determination of conditional partition constants in an FIA system. AB - This paper presents a simple and rapid method for the screening of substances for their conditional partition constants in the chloroform-water system. Samples are injected in either aqueous or organic solution into the corresponding phase. After equilibration in segmented flow the amount of sample remaining is measured photometrically. Performing the measurements at a series of phase volume ratios enables calculation of conditional partition constants knowing neither the amount injected nor the absorptivity of the substance under study. The time needed for a determination is about 15 min per substance, in many cases even shorter and the sample consumption is, in most cases, less than 1 mg. These characteristics make the method suitable for screening purposes. A series of compounds has been examined with this method, and acceptable results for the conditional partition constants were obtained in the range 0.2 less than D' less than 100 (-0.7 less than log D' less than 2.0). PMID- 1420463 TI - Determination of thevetin B in serum by fluorescence polarization immunoassay. AB - Thevetin B, a cardiac glycoside of Thevetia neriifolia Juss. seeds, was determined in serum by fluorescence polarization immunoassay. Anti-digitoxin antibody was used, thevetin B genin being structurally identical to digitoxigenin. Cross-reactivity of 94% was found by this method, for concentrations from 5 to 80 ng ml-1. PMID- 1420464 TI - Colorimetric and titrimetric assay of isoniazid. AB - Two methods are proposed for the determination of isoniazid in pure form or in tablets. In the first method chlorpromazine hydrochloride, when treated with 2 iodoxybenzoic acid as an oxidant in 50% w/v o-phosphoric acid solution, is oxidized to chlorpromazine free radical which absorbs at 530 nm. The red free radical is readily reduced quantitatively by isoniazid to the colourless chloropromazine. The addition of isoniazid to a red solution of chlorpromazine free radical results in a decrease in absorbance in direct proportion to the quantity of isoniazid. This forms the basis for the quantitative determination of micro-quantities of isoniazid (3-18 micrograms ml-1). The second method involves the titrimetric determination of isoniazid using N-bromophthalimide as a titrant. The end-point is determined either directly using methyl red or amaranth as indicator, or by a back titration method in which a known excess of N bromophthalimide solution is added to isoniazid solution and then the residual unreacted reagent is determined iodometrically. The results by the proposed procedures were in good agreement with those obtained by the official methods. PMID- 1420465 TI - Determination of 9-hydroxyellipticine by redox colorimetry. AB - The chemical reactions involved in the decomposition of 9-hydroxyellipticine (9 OH-E), an anticancer agent, in polar solvents is explained. The reactions, which involve the formation of 9-oxo-ellipticine and the addition of a nucleophilic acid on the C10 site of the heterocyclic system, have been used to measure 9-OH-E quantitatively by colorimetry in solution and by reflection on paper surfaces. A method for the stabilization of 9-OH-E in polar solvents is proposed. PMID- 1420466 TI - The identification of related substances in 9 alpha-fluoroprednisolone-21 acetate by means of high-performance liquid chromatography with diode array detector and mass spectrometry. AB - A method for the analysis and identification of the principal related substances in 9 alpha-fluoroprednisolone acetate is described. This compound has been chosen as a model for the investigation of related substances which can be originated in the general procedure for introducing a fluorine substituent at position 9 of a corticosteroid molecule. HPLC procedures, both in reversed and in normal phase were used; a rapid scanning UV detector which allows direct spectrophotometric data to be obtained on chromatographic peaks, proved to be a tool of great importance. Thus, after reversed-phase chromatographic separation and observation of the UV spectra and their respective second derivatives, it was possible to characterize some of the principal effective and potential related substances such as 9 alpha-fluorohydrocortisone acetate, 9 alpha-bromoprednisolone acetate, 9 beta, 11 beta-epoxyprednisolone acetate and 9(11)-dehydroprednisolone acetate, emerging as chromatographic peaks. Identification of 9 alpha-bromoprednisolone acetate and of 9 alpha-fluorohydrocortisone acetate which proved to be the most significant impurities, was confirmed by means of an exhaustive study of the mass spectra of these substances conveniently isolated by normal-phase HPLC. The chromatographic, spectrophotometric and mass-spectrometric characteristics of the studied compounds are reported. PMID- 1420467 TI - Liquid chromatographic resolution of the isomers of tipredane and phenylthioproline using urea-solubilized beta-cyclodextrin in the mobile phase. AB - Two LC assays were developed using urea-solubilized beta-cyclodextrin (beta-CD) as a mobile phase additive in combination with reversed-phase columns. A methylsilane column gave optimal resolution of the steroid tipredane from its epimer. An investigation of the effects of beta-CD concentration, column temperature, column type, and addition of ethanol on the chromatographic separation is detailed. The enantiomer and diastereoisomers of L-cis phenylthioproline were best resolved by urea-solubilized beta-cyclodextrin and a trimethylsilane column. The elution order of L-cis-phenylthioproline relative to its stereoisomers was reversed after adding ethanol to the beta-CD containing mobile phase or by changing from a beta-CD to an acetylated beta-CD column. The resolution factors for these separations obtained using the beta-CD mobile phase were larger than those obtained using beta-CD columns. Mobile phases containing up to 0.15 M beta-CD and 8 M urea were investigated. The separation of these isomers are dramatically affected by column polarity. PMID- 1420468 TI - Thermal decomposition of reduced glutathione in solution for organ preservation. PMID- 1420469 TI - Isolation and characterization of the S-glucuronide of 4-nitrothiophenol formed by microsomal glucuronyl transferase. PMID- 1420470 TI - Analysis of 3- and 4-monopivaloylepinephrine, degradation products in dipivefrin hydrochloride drug substance and ophthalmic formulations. PMID- 1420471 TI - A competitive enzyme immunoassay for the direct determination of mometasone furoate (SCH 32088) in human plasma. AB - Mometasone furoate (SCH 32088) is a synthetic corticosteroid which has a topical anti-inflammatory activity with a minimal potential for suppressing hypothalamic pituitary-adrenocortical (HPA) axis. A sensitive competitive enzyme immunoassay (EIA) for measuring SCH 32088 in unextracted human plasma has been developed. The 3-(O-carboxymethyl)oxime (CMO) of SCH 32088 was synthesized and conjugated with bovine thyroglobulin, and the product was used for the production of antibodies in rabbits. SCH 32088-3-CMO was also conjugated with horseradish peroxidase, which was used as the tracer. The EIA thus developed can detect 1 pg SCH 32088 per assay or 25 pg per ml of human plasma. It can reliably quantitate SCH 32088 in human plasma from 50 pg ml-1 to 2.5 ng ml-1 with good linearity, accuracy and precision. The assay can be extended to measure SCH 32088 in plasma of laboratory animals. The availability of this sensitive assay makes it possible to evaluate the pharmacokinetics and toxicokinetics of SCH 32088 in laboratory animals and man. PMID- 1420472 TI - Use of derivatization reactions with adsorptive stripping voltammetry for determining fotemustine in biological samples. AB - A method is described for determining the new fotemustine antineoplastic in human serum. The method is based on the derivatization of the original molecule by means of diazotization and coupling reactions. The derivatization product is determined by means of adsorptive stripping voltammetry. The calibration graphs were linear over the range 6 x 10(-9)-8 x 10(-7) and 6 x 10(-10)-8 x 10(-8) M, according to whether the coupling reagent was 1-naphthylamine or 1-naphthol, respectively. At the same time, the detection limits are 4.1 x 10(-9) and 1.4 x 10(-10) M, respectively. The method was applied to determine this antineoplastic in human serum, after a liquid-liquid extraction process, from which recovery factors of 95.6% has been obtained. PMID- 1420473 TI - Fundamental studies in reversed-phase liquid-solid extraction of basic drugs; III: Sample matrix effects. AB - Using a set of 13 basic solutes (including a quarternary ammonium compound) with controlled pKa, log P and plasma protein binding, the factors which influence the extraction of these compounds from plasma by reversed-phase liquid-solid extraction have been studied. Direct analysis of plasma, avoiding deproteination, etc., is possible providing the sample is applied to the cartridge under the appropriate conditions. These conditions are dictated by the degree of plasma protein binding and are controlled and predicted from the lipophilicity of the compound. Plasma samples containing lipophilic compounds (log D(pH 7.4) > 2.03) require acidification and samples containing more polar compounds (log D(pH 7.4) < 0.9) should be applied untreated. Failure to use the appropriate conditions can result in significant losses from the cartridge on application or washing. In the intermediate lipophilicity range the optimal application conditions cannot be predicted. The effect of various aqueous-organic wash solvents have been investigated, and it was found that the cationic but not the proteinaceous components of plasma also affect the extraction process. This phenomenon which is probably due to an attenuation of the secondary cation exchange mechanism, results in more facile elution than when compounds are applied in water. PMID- 1420474 TI - Relationships between the chromatographic retention data and the effects of nucleoside derivatives in highly metastatic 3LL cells. AB - The effect of 21 nucleoside derivatives on the [3H]-thymidine cellular uptake and on the incorporation into DNA of highly metastatic 3LL (Lewis lung carcinoma) cells has been measured. Hydrophobic and hydrophilic molecular parameters (the adsorption capacity, specific adsorption surface, lipophilicity and specific hydrophobic surface area) have been determined by using thin-layer chromatography. Stepwise linear regression analysis and principal component analysis have been applied in order to reveal the relationships between the molecular parameters and the effect of the nucleoside derivatives on highly metastatic 3LL cells. The first principal component obtained from the measured activity data could be attributed to the change of [3H]-thymidine cellular uptake caused by the nucleoside, while the second principal component could be regarded as the measure of the effect on the DNA incorporation of [3H]-thymidine. The effect of the nucleosides on the [3H]-thymidine uptake could be explained by the specific hydrophobic and adsorption surface area of the nucleoside, on the other hand the effect on the DNA incorporation could be described by the adsorption characteristics (specific hydrophilic surface area and adsorption capacity) of the derivatives. PMID- 1420475 TI - The enantiomeric resolution of ciprofibrate and related compounds by HPLC using chiral stationary phases. AB - The attempted chromatographic resolution of the drug ciprofibrate and a range of related compounds, containing the chiral moiety 2,2-dichlorocyclopropylbenzene, using five different chiral stationary phases is described. Aqueous mobile phases were used throughout and the successful separation of nine out of 12 pairs of enantiomers was achieved. Structures remote from the chiral centre were seen to affect chiral recognition. PMID- 1420476 TI - Ion-pair high-performance liquid chromatographic determination of morphine and pseudomorphine in injections. AB - A stability-indicating HPLC procedure has been developed for the determination of morphine and its degradation product pseudomorphine in injection solutions. The reversed-phase chromatographic procedure uses an octadecyl-bonded column with a mobile phase of acetonitrile and aqueous buffer containing an ion-pair reagent. Chromatographic conditions are identified that enable the complete separation of morphine and pseudomorphine without peak deformation or splitting. The only sample preparation required is a simple dilution. The method is found to be precise and linear. The devised method has been applied to the determination of the content of morphine and pseudomorphine in injection solutions stored under normal conditions and after exposure to daylight or heating at 60 degrees C. PMID- 1420477 TI - Determination of glutathione isopropyl ester in rat, dog and human blood by high performance liquid chromatography with fluorescence detection. AB - A HPLC method is developed for the determination of glutathione isopropyl ester, a drug for the treatment of cerebral vascular disease, in rat, dog and human blood. The blood is deproteinized with sulphosalicylic acid and the clear supernatant treated with a thiol-specific fluorogenic reagent, ammonium 7 fluorobenzo-2-oxa-1,3-diazole-4-sulphonate (SBD-F) in borate buffer pH 7.5 at 30 degrees C. The derivatization of glutathione isopropyl ester with SBD-F is markedly enhanced by the addition of dimethyl sulphoxide, and is complete in 30 min. The fluorescent derivatives of glutathione isopropyl ester and the internal standard, glutathione ethyl ester are separated from those of endogenous thiols such as cysteine and glutathione on a reversed-phase column. The method is simple and selective with a detection limit of 0.05 micrograms ml-1. Blood concentrations of glutathione isopropyl ester in rats, dogs and humans after intravenous administration are determined using the method. PMID- 1420478 TI - Spectrophotometric determination of famotidine in pharmaceutical preparations. PMID- 1420479 TI - Determination of cephradine and L-arginine in injections by second derivative ultraviolet spectrophotometry. PMID- 1420480 TI - Determination of quinine in some pharmaceutical preparations using a ring-coated piezoelectric sensor. PMID- 1420481 TI - A study of the photodegradation of benzydamine in pharmaceutical formulations using HPLC with diode array detection. PMID- 1420482 TI - A liquid chromatographic method for the determination of hydrochlorothiazide in human plasma. PMID- 1420483 TI - [A methodology for clinical trials in parenteral nutrition]. AB - Recent and progressive knowledge on parenteral nutrition has not been accompanied by due attention to the methodology for clinical testing in this therapeutical field. Although many different laws, guidelines or norms do exist which can be applied to any clinical test, in the case of parenteral nutrition several characteristic aspects arise that should be taken into account in the design of clinical tests. This review places special emphasis on the definition of clinical testing, the role of the researcher and the ethical, methodological and design related requirements to be considered when preparing a protocol for study. Not only is the importance of the selection and the size of the sample mentioned, but also the different variables normally used in parenteral nutrition. The correct follow-up, measurement, evaluation and statistical analysis of these variables makes it possible to reach valid conclusions, and provide the basic information for later study. The application of ethical norms and the control of adverse conditions guarantees the correct undertaking of this type of clinical research. PMID- 1420484 TI - [The methodology of quality control in parenteral nutrition. II. The application of the program to a therapeutic plan]. AB - Patients subjected to parenteral nutrition (PN) must be treated based on a therapeutical plan which has been adapted to their nutritional and clinical needs within a normalizing framework. Furthermore, for this therapeutical plan to be effective and safe, not only must it be suitable for the patient, but also "exact" with regard to daily routines. The quality control programme designed was applied retrospectively to 148 patients. Evaluation was made based on the following indicators: a) delay in initiating parenteral nutrition, b) average intake of macronutrients, c) administration of micronutrients, d) duration of the PN, e) temporary interruptions of the PN, f) errors in medication and g) return of nutrient units. The compliance percentage obtained was 100, 100, 28.7, 89.5, 63.2 100 and 100 respectively. The results obtained have made it possible to understand the quality profile of the therapeutical plan applied to patients on PN. It is also a useful method for the continued improvement of this therapy. PMID- 1420485 TI - [The Iberian pig: an animal with fat with a high content of monounsaturated fatty acids]. AB - We have analyzed the fatty acid composition of subcutaneous fat in the Iberian pork feed with acorns using gas chromatography. We have found a 59.1% content in oleic acid (18:1) and 62% of total monounsaturated fatty acids. This figures statistically does differs from the data about fat composition in pig taken from others food composition sources. We conclude that Iberian pork feed with acorns have a very high content in monounsaturated fatty acids and can no be considered as harmful as other animals fats. PMID- 1420486 TI - [Changes in the biochemical parameters during parenteral nutrition. The experience in Hospital de Bellvitge]. AB - The purpose of this study is to evaluate the modifications in biochemical parameters before and after the initiation of nutritional therapy, and to observe whether there is a relationship between the patient's development (exitus or improvement) and the presence of sepsis. The study was performed on 578 adults treated in our hospital from January 1988 to October 1989. The parameters analyzed were the following: glucose, triglycerides, total proteins, albumin, cholesterol, alkaline phosphatase, GOT, GPT, bilirubin, GGT, urea, urates, creatinine and electrolytes. The average initial values of each parameter were compared against those obtained after interrupting the PN by means of the Student t test. The results showed that within the parameters indicating the hepatic function, GGT and alkaline phosphatase were those that showed the most significant differences after ceasing the PN. Furthermore, the parameters indicating hepatic function and the electrolytes showed greater variations, regardless of the clinical evolution of the patient (improvement or exitus). The remainder of the parameters showed significant variations based on the clinical evolution. PMID- 1420487 TI - [Enteral nutrition in burn patients]. AB - Nutritional support plays an important role in the treatment of patients with burns. Due to the severe hypercatabolism that develops in these patients, oral support is insufficient in most cases, and this makes it essential to initiate artificial nutritional support (either enteral or parenteral). Enteral nutrition is more physiological than parenteral, and data exist which show that in patients with burns, enteral nutrition exercises a protective effect on the intestine and may even reduce the hypermetabolic response in these patients. The purpose of the study was to evaluate the effectiveness and tolerance of enteral nutritional support with a hypercaloric, hyperproteic diet with a high content of branched amino acids in the nutritional support of patients suffering from burns. MATERIAL: The study included 12 patients (8 males and 4 females), admitted to the Burns Unit. Average age was 35 +/- 17 years (range: 21-85 years). The percentage of body surface affected by the burns was 10% in two cases, between 10-30% in three cases, between 30-50% in five cases and over 50% in two cases. Initiation of the enteral nutrition was between twenty-four hours and seven days after the burn. The patients were kept in the unit until they were discharged, and the average time spent in the unit was 31.5 days (range: 17-63 days). Total energetic requirements were calculated based on Harris-Benedict, with a variable aggression factor depending on the body surface burned, which varied from 2,000 and 4,000 cal day. Nitrogenous balance was determined on a daily basis, and plasmatic levels of total proteins, albumin and prealbumin on a weekly basis. RESULTS: There was a significant difference between the prealbumin values at the initiation and finalization of the enteral nutrition (9.6 +/- 2.24 mg/dl compared with 19.75 +/- 5.48 mg/dl; p < 0.001). The nitrogenous balance improved, changing from -5.4 in the second week to positive values by the fourth and fifth weeks of treatment. Tolerance to the enteral diet was very good, and only mild complications such as diarrhoea developed in two patients. CONCLUSIONS: Enteral nutrition is a suitable nutritional support method for patients with burns, which maintains the nitrogenous balance positive and improves the visceral protein parameters in these patients at an early stage, with very few complications. PMID- 1420488 TI - [Percutaneous and surgical gastrostomies: our clinical experience in enteral nutrition]. AB - Percutaneous gastrostomy (PG) was performed on 18 patients and 11 patients were subjected to surgical gastrostomy (SG) in the HCU of Zaragoza from October 1990 to November 1991. Involvement of the high digestive tract was the most common finding: 11 patients had CA of the oesophagus and stomach, 2 suffered from extrinsic pressure of the oesophagus due to metastatic adenopathy of a lung and breast tumour and 9 patients had CA of the larynx with total dysphagia. Another less common indication in our series, although still of great importance, was a severe involvement of the CMS, which made oral nutrition impossible due to functional dysphagia. Due to the long-term nature of this pathology, feeding by nasogastric tube was not considered. This was the case of 4 patients. The duration of enteral nutritional in the patients' home was 112.8 +/- 61 days with PG and 37 +/- 26 days with SG (p: 0.007). The incidence of complications was 33% in PG and 73% in SG, and for both techniques, the most common complication was blockage of the tube. Percutaneous gastrostomy is a simple technique, with no surgical risks involved, but with the benefits of traditional surgical techniques which, despite the small number of cases recorded, has very few complications both with regard to placing and afterwards, and also enables the patient to receive nutrients earlier than would be the case with traditional surgical techniques during prolonged periods at the patient's home. PMID- 1420489 TI - Small solute clearances and clinical outcomes in CAPD. AB - The strong correlation of weekly clearances of urea and creatinine with PCR suggests that minimum targets of 50 L/week/1.73 m2 body surface area of creatinine clearance and a weekly kt/v urea of 1.7 are reasonable if protein intakes in excess of 0.8 g/kg normalized body weight are to be achieved in most CAPD patients. It would seem reasonable that this increases the chances for better nutrition. It would also seem reasonable that this should eventually improve long-term outcomes and survival in large population studies where the impact of dialysis dose could emerge as significant, even with the presence of all the other variables that are known to affect commonly monitored outcome parameters. These recommended targets are well below those achieved by hemodialysis; higher targets could possibly achieve even better long-term results, but this is unknown. PMID- 1420490 TI - Lubrication of the peritoneum. PMID- 1420491 TI - Erythropoietin and peritoneal dialysis: the efficacy of intraperitoneal dosing. PMID- 1420492 TI - Is total creatinine clearance a good predictor of clinical outcomes in continuous ambulatory peritoneal dialysis? AB - The measurement of the adequacy of dialysis in continuous ambulatory peritoneal dialysis (CAPD) is controversial. The use of weekly total creatinine clearance (TCC) has been recommended, but not validated. We analyzed data from our recent urea kinetics in a CAPD study to investigate TCC and its relationship to patient outcomes. TCC was measured over 24 hours by adding residual renal and peritoneal creatinine clearance, correcting for 1.73 m2 surface area and converting to a weekly value. Seventy-six patients had 218 measurements, on starting CAPD and then at 6-month intervals, with mean follow-up of 20 months (range 1-57 months). The mean TCC was 73.62 +/- 32.11 L/week. Due mainly to the loss of residual renal function, the TCC decreased with time (r = -0.40, p < 0.0001), from 88.65 L/week initially to 66.11 at one year, 59.84 at two years, and 50.47 at three years. Dialysate-to-plasma creatinine concentration ratios (D/P Cr) increased with time (r = 0.28, p < 0.0001) from 0.62 initially to 0.66 at one year and 0.73 at two years. The TCC correlated significantly with serum levels of creatinine (r = 0.46, p < 0.0001), urea (r = -0.21, p < 0.001), potassium (r = 0.14, p < 0.05), phosphate (r = 0.25, p < 0.001), and hemoglobin (r = 0.16, p < 0.01), but not with serum albumin or with clinical outcomes including technique failure, hospital days, transfusions, peritonitis rate, nerve conduction velocity, or subjective indices of well-being, except for a weak correlation with the fatigue index (r = 0.19, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420493 TI - Intraperitoneal administration of phosphatidylcholine improves ultrafiltration in continuous ambulatory peritoneal dialysis patients. AB - Reports in the literature have linked a low phosphatidylcholine content in continuous ambulatory peritoneal dialysis (CAPD) effluent to ultrafiltration loss. Clinical evidence suggests that adding phosphatidylcholine to the dialysis solution enhances ultrafiltration. A clinical study has been designed to clarify the effect of phosphatidylcholine on ultrafiltration in CAPD patients with normal ultrafiltration. A weekly measurement of the peritoneal equilibration test was conducted per patient in the hospital. A comparison between the control dialysis solution (three-week period) and the phosphatidylcholine premixed solution (three week period) was performed on a total of 12 patients. This study shows that a phosphatidylcholine premixed dialysis solution significantly enhances ultrafiltration. Since ultrafiltration per osmotic driving force (mL/g glucose) is enhanced, the patient's glucose load per day is reduced to achieve equal ultrafiltration. In the presence of phosphatidylcholine, peritoneal permeability remained unchanged, as indicated by membrane transport characteristics. No side effects were observed. PMID- 1420494 TI - Dialysis at home in the west of Scotland: a comparison of hemodialysis and continuous ambulatory peritoneal dialysis in age- and sex-matched controls. AB - OBJECTIVE: To audit the outcome of patients treated at home by hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective comparison of nondiabetic hemodialysis patients with age- and sex-matched nondiabetic patients treated by CAPD. SETTING: Renal Units, Stobhill General Hospital and Western Infirmary, Glasgow, providing the home dialysis service for the West of Scotland. PATIENTS: Between 1982 and 1988, 139 hemodialysis patients starting treatment at home, compared with 139 matched patients starting CAPD over the same time period. MAIN OUTCOME MEASURES: Patient characteristics and cardiovascular risk factors at the start of home treatment. Patient and technique survival with both forms of dialysis. RESULTS: Patients selected for home hemodialysis were less likely to be smokers (p < 0.02) and to have electrocardiographic evidence of ischemia or left ventricular hypertrophy (p < 0.05) than patients treated by CAPD. Patient survival and technique survival (excluding death and renal transplantation) at 3 years were 93.8% versus 86.2% (p < 0.05) and 94.2% versus 80.8% (p < 0.04) for hemodialysis and CAPD, respectively. Cardiovascular events were responsible for the majority of deaths in both groups, but there was a greater proportion of deaths from other causes in patients treated by CAPD. There was no significant difference in the transplantation rate between the two treatment groups. CONCLUSIONS: Home dialysis is an effective method of renal replacement treatment for patients with end-stage renal disease. The results of hemodialysis are superior to CAPD, but this may be partly due to selection bias. PMID- 1420495 TI - The pharmacokinetics of intraperitoneal erythropoietin administered undiluted or diluted in dialysate. AB - OBJECTIVE: To compare the bioavailability of intraperitoneal erythropoietin (EPO) administered undiluted versus diluted in 2 L of dialysis fluid. DESIGN: Group 1 patients received one dose of EPO, 400 U/kg BW given with vehicle only. This dwelled for 8 hours after which 2 L of dialysate were infused. Group 2 patients received the same dose of EPO diluted in 2 L of dialysate which dwelled for 8 hours. Both groups resumed their CAPD regimen after the first 8 hours. Blood levels of EPO were measured for 24 hours in both groups. SETTING: The Home Peritoneal Dialysis Unit, Toronto Hospital, Western Division. PATIENTS: The participants were on CAPD for at least three months, free of peritonitis, and had no abnormalities of peritoneal transport. Three patients took part in both arms of the study, and there were 6 patients altogether in each group. RESULTS: When EPO was administered undiluted, there was a greater than ninefold increase in bioavailability of the hormone as measured by the area under the curve (AUC), compared to when the same dose was diluted in 2 L of dialysis fluid. CONCLUSIONS: The previous studies that reported low bioavailability of intraperitoneal EPO used the hormone diluted in dialysate. The current findings suggest that if EPO is given in the dry peritoneal cavity, the bioavailability is greatly improved and may be clinically effective. Intraperitoneal instillation may prove to be an alternative route for EPO in the peritoneal dialysis patient unable or unwilling to receive subcutaneous injections. We are currently studying the effectiveness of undiluted intraperitoneal EPO in CAPD patients. PMID- 1420496 TI - Effect of erythropoietin in continuous ambulatory peritoneal dialysis patients: comparison between intravenous and intraperitoneal administration. AB - The administration of recombinant human erythropoietin (rHuEPO) in CAPD patients is usually done subcutaneously. Only a few authors have reported on its intraperitoneal (IP) administration. We compared the effect of IP administration of rHuEPO in CAPD patients to that of intravenous (IV) administration. Ten anemic CAPD patients injected rHuEPO into their dialysis bag once a day, 3 times a week, for 18 weeks. The initial dose was 12,000 U. The dwell time of the exchanges with rHuEPO was about 6 hours. Nine other anemic CAPD patients were treated with IV rHuEPO once a week for 18 weeks. The initial dose was 6000 U. In the IP group the hematocrit rose from 24.04 +/- 2.7% to 33.3 +/- 3.8% (mean +/- SD). In the IV group 2 patients were excluded from the efficiency evaluation. In 7 of the 9 patients in the IV group, the hematocrit rose from 23.27 +/- 2.6% to 32 +/- 5.5% (mean +/- SD). The intraperitoneal administration of rHuEPO in CAPD patients is sufficient in improving anemia, although it requires a much larger dosage to yield the same level of improvement as the one obtained with the intravenous administration. However, in patients on continuous cycling peritoneal dialysis or IP dialysis, a smaller dosage during the prolonged dwell time may be effective. PMID- 1420497 TI - Intraperitoneal administration of recombinant human erythropoietin. AB - OBJECTIVE: To determine the efficacy and safety of intraperitoneal administration of recombinant human erythropoietin (rHuEPO) in continuous ambulatory peritoneal dialysis (CAPD) patients compared to subcutaneous rHuEPO. DESIGN: Prospective analysis of an open, nonrandomized investigation. SETTING: Outpatient CAPD clinics in two university hospitals. PATIENTS: Nine adult CAPD patients receiving rHuEPO intraperitoneally and 8 patients receiving rHuEPO subcutaneously. INTERVENTION: One hundred units of rHuEPO per kilogram of body weight were administered three times a week for 8 weeks or until the target hematocrit of 35% was reached. Thereafter, dosages of rHuEPO were adjusted for response. Intraperitoneal rHuEPO was administered in 1 L of dialysis solution during the night. MEASUREMENTS: Efficacy was assessed by measuring the increase in hemoglobin. Tolerance was assessed by monitoring side effects. RESULTS: In the first 8 weeks of treatment hemoglobin concentration increased from 64.5 +/- 12.9 g/L to 98.3 +/- 16.1 g/L (p < 0.0005) in the intraperitoneally treated group. In the subcutaneously treated group hemoglobin increased significantly faster (p < 0.05) from 72.5 +/- 4.8 g/L to 119.2 +/- 11.3 g/L (p < 0.0005) in the same period. Antihypertensive medication had to be increased or instituted in most of the patients in both groups. The incidence of peritonitis in the intraperitoneally treated group was not increased when compared to the pretreatment incidence. CONCLUSIONS: Subcutaneously administered rHuEPO is superior to intraperitoneally administered rHuEPO with regard to the required dosages. However, the results of this study show that intraperitoneal administration of rHuEPO might be a convenient and safe alternative when subcutaneous administration is undesirable. PMID- 1420498 TI - Six-year experience with swan neck catheters. AB - From the beginning of our continuous ambulatory peritoneal dialysis (CAPD) program in January 1977 until June 1985, we used Tenckhoff and Toronto Western Hospital catheters. Throughout these years catheter survival probabilities of about 30% at three years persisted unchanged and were similar to survival probabilities reported by the National CAPD Registry special survey for these catheters. The first improvement in catheter results regarding leaks was noted after the adoption of lateral catheter insertion. Malfunction was less using swan neck prototypes from August 1985 to April 1986. The latter catheters were made of 80 degrees arc angle tubing between 8.5 cm spaced cuffs and were inserted in a reversed U-shape tunnel with the incision at the top of the tunnel. The use of these catheters was abandoned because of high cuff extrusion and exit infection rates. The next generation of swan neck catheters, the swan neck Missouri 2 and 3 catheters with straight intraperitoneal segments, improved the results dramatically. These catheters were made of 180 degrees arc angle tubing between 5 or 3 cm spaced cuffs. The estimated survival probability of 61% at three years more than doubled compared to previously used catheters. Recently we modified the intraperitoneal segment of the catheters, replacing the straight segment with a coiled one. These modified catheters, the swan neck Missouri coiled catheters, have been used exclusively since February 1990. In addition to an acceptable survival probability of 88% at one year, there are two major advantages of these catheters, the same as for other coiled catheters: elimination of infusion pain due to a jet effect and pain related to straight catheter tip pressure on the peritoneum experienced by some patients. PMID- 1420499 TI - A 45-year-old black female on peritoneal dialysis with chronic abdominal pain. PMID- 1420500 TI - Bowel perforation in CAPD patients. PMID- 1420501 TI - CAPD after aortic graft surgery. PMID- 1420502 TI - Does posture modify solute transport in CAPD? PMID- 1420503 TI - Literature. October-December 1992. PMID- 1420504 TI - The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study. AB - One hundred and forty one patients were treated in a combined Eastern Cooperative Oncology Group and Southwest Oncology Group phase-III study evaluating low-dose cytarabine (LDAC) versus supportive therapy for the treatment of myelodysplastic syndrome (MDS). Patients were randomized to either cytarabine 10 mg/m2 subcutaneously BID or supportive therapy. Central pathology review was required. All patients were classified according to the FAB criteria for MDS. The overall concordance rate for the MDS subtype was 52%, and 25 patients were pathology exclusions, including 20 with AML. The overall response rate to a single cycle of LDAC was 32%, with 11% complete and 21% partial responses. The median duration of response was 5.9 months, with a range of 1.4-33.5 months. Responses were seen in all subtypes. Infections were more common in the LDAC arm. There was no difference in the time to progression or the overall survival for patients treated with LDAC or supportive therapy. The incidence of leukemic transformation was similar in both arms at 15%, but it differed according to the MDS subtype. Patients receiving LDAC had a decreased transfusion requirement after 3 months. There was a significant correlation between the degree of cytoreduction after receiving a single cycle of LDAC and survival. This survival difference was most marked in patients with the RAEB and RAEB-T subtypes. Although LDAC produced responses in all subtypes of the MDS, there was no effect on overall survival or transformation to AML. However, selected patients benefited from a single cycle of LDAC with durable responses. A cytoreductive effect appears to be required for a durable response. Future studies should include pathology review and must address the clinical and biological heterogeneity of MDS. PMID- 1420505 TI - A major concanavalin-A-binding cell surface protein from normal and leukemic granulocytes: isolation and characterization. AB - This paper reports the isolation and biochemical characterization of a major concanavalin A (Con A)-binding cell surface protein (protein 2, M(r) 75-85 kD) from normal and chronic myeloid leukemic (CML) granulocytes. Our studies show that protein 2 has two differentially glycosylated forms, protein 2a (M(r) 75-85 kD), which does not bind the lectin RCA, and protein 2b (M(r) 80-90 kD), which does. Both molecules show identical retention times on reverse-phase HPLC, irrespective of the cell source. By the procedure used the amount of 2a obtained is about 2.4 times more than that of 2b in normal cells and about 2.6 times more in CML cells. Furthermore, both are approximately 2.4-fold more in CML granulocytes. A polyclonal antibody to protein 2a also immunostains protein 2b. The antibody to protein 2a does not prevent Con A binding but inhibits its internalization. Similarity of the molecules from both the cell types and their increased amounts in CML granulocytes suggest that factors/components other than its structure and amount are responsible for the known defective internalization of Con A by CML granulocytes. PMID- 1420506 TI - Flow-cytometric enumeration of reticulocytes with the new fluorochrome 1,3' diethyl-4,2'-quinolylthiacyanine (correction of 1',3'-diethyl-4,2' quinolylthiacyanine) AB - Several flow-cytometric methods for reticulocyte enumeration in whole blood have been developed, with different degrees of practical use. Recently, a new fluorochrome, 1,3'-diethyl-4,2'-quinolylthiacyanine (corrected) (DEQTC) was proposed in a brief report, as an alternative to thiazole orange for reticulocyte counting. We have evaluated the usefulness of this fluorescent stain by assessing the optimal conditions for the flow-cytometric analysis, and by comparing in double-blind assays the quantitative results of this technique with those obtained by manual counting with brilliant cresyl blue. Our results show that flow cytometry with DEQTC is highly correlated to the manual method (r = 0.95 0.99), supporting the interest of this particular stain and of flow cytometry for routine laboratory work in hematology. PMID- 1420507 TI - Rapid molecular characterization of mutations leading to unstable hemoglobin beta chain variants. AB - Characterization of unstable hemoglobins by protein analysis is often difficult. However, it is facilitated by DNA analysis, especially in the case of hyperunstable beta-chain variants, which produce a beta-thalassemia phenotype. We have applied an efficient strategy to the detection of such variants at the DNA level, based on computer-designed denaturing gradient gel electrophoresis (DGGE) of amplified DNA fragments. This approach makes it possible to detect any anomaly in the beta-globin gene. We describe the use of the DGGE method for rapid characterization of beta-chain variants and report a new missense mutation in the beta-globin gene third exon, beta 127 CAG-CGG/Gln-Arg, which is responsible for the synthesis of a highly unstable hemoglobin. PMID- 1420508 TI - Mediastinal extramedullary hematopoiesis as first manifestation of hereditary spherocytosis. PMID- 1420509 TI - Use of intravenous immunoglobulins (IVIg) to treat a child with pancytopenia and hypoplastic marrow. PMID- 1420510 TI - Converging toward a "unified field theory" of epidemiology. PMID- 1420511 TI - Medicare studies of vertebral fractures. PMID- 1420512 TI - A definition of bias founded on the concept of the study base. AB - We propose a definition of bias founded on the concept of the study base. The definition is unrelated to the study design, thereby permitting a clear comparison of validity among different study types. Also, it facilitates assessment of bias because it allows bias to be subdivided under mutually exclusive categories. In relation to the study base, the epidemiologic study can be viewed as involving three distinct steps. First, the person-time (study base) is specified for the study. Second, the investigators collect data on disease events and person-time among the exposed and unexposed from the study base. Third, they calculate an estimate of the effect of the exposure using the data. Categories pertaining to each of these three steps will create mutually exclusive categories of bias. We suggest the following terminology: the first step generates confounding, the second results in misclassification and misrepresentation, and the third produces analysis deviation. The total bias is the sum of the confounding, misclassification, misrepresentation, and analysis deviation. We illustrate our proposed epidemiologic theory with examples from various biological settings. PMID- 1420513 TI - Renal cell cancer among paperboard printing workers. AB - A physician's alert prompted us to investigate workers' cancer risk at a paperboard printing manufacturer. We conducted a retrospective cohort mortality study of all 2,050 persons who had worked at the facility for more than 1 day, calculated standardized incidence ratios (SIRs) for bladder and renal cell cancer, and conducted a nested case-control study for renal cell cancer. Standardized mortality ratios (SMRs) from all causes [SMR = 1.0, 95% confidence interval (CI) = 0.9-1.2] and all cancers (SMR = 0.6, 95% CI = 0.3-1.0) were not greater than expected. One bladder cancer and one renal cell cancer were included in the mortality analysis. Six incident renal cell cancers were observed, however, compared with less than two renal cell cancers expected (SIR = 3.7, 95% CI = 1.4-8.1). Based on a nested case-control analysis, the risk of renal cell cancer was associated with overall length of employment but was not limited to any single department or work process. Although pigments containing congeners of dichlorobenzidine and o-toluidine had been used at the plant, environmental sampling could not confirm any current exposure. Several limitations and a potential selection bias limit the inferences that can be drawn. PMID- 1420514 TI - Evaluation of three nutritional assessment methods in a group of women. AB - We conducted a reproducibility study of four 24-hour dietary recalls (N = 224) and four biochemical assessments of nutritional status (N = 265) in a group of women in Alabama. For 24-hour recalls, the variance component ratios were all greater than 1, and the intraclass correlation coefficients ranged from 0.16 to 0.27 for macronutrients, and from 0.09 to 0.37 for vitamins and minerals. The intraclass correlation coefficients for biochemical assessments ranged between 0.39 and 0.74 with corresponding variance component ratios of 1 or below for most nutrients. The correlation coefficients between the food frequency questionnaire on the usual dietary intake during the year preceding the beginning of study and the mean values of four 24-hour dietary recalls administered at the initial visit and again after 2, 4, and 6 months ranged from 0.3 to 0.4 for most nutrients. We found plasma beta-carotene levels to be moderately correlated with dietary vitamin A (r = 0.20) and beta-carotene (r = 0.22). PMID- 1420515 TI - Assessing consumption of high-fat foods: the effect of grouping foods into single questions. AB - Questionnaires on the frequency of consumption of foods are commonly used to measure dietary intake in epidemiologic research. To reduce the burden on respondents, questionnaires are often shortened by combining inquiries on similar foods into a single question. The effect of this practice on the reporting of dietary intake has never been investigated, however. To address this issue, we used two food frequency questionnaires in a telephone survey designed to rank adult residents of Alabama by their intake of dietary fat. One questionnaire included 29 questions about separate high-fat foods, whereas the other grouped these same foods into 14 questions. Compared with the 443 respondents interviewed using the 29-item separated-foods questionnaire, the 465 respondents responding to the 14-item grouped-foods questionnaire reported lower average intakes of the foods. In addition, a substantially higher percentage of respondents to the grouped-foods questionnaire reported never consuming the foods. PMID- 1420516 TI - Passive smoking in Germany and Poland: comparison of exposure levels, sources of exposure, validity, and perception. AB - Nonsmoking females age 35-65 years from Bremen, Germany (91 women), and Opole, Poland (98 women), were interviewed about their recent passive smoking exposure. We obtained urine samples at the time of interview and determined the concentration of cotinine as an indicator of tobacco smoke exposure. In Poland and in Germany, the vast majority of nonsmoking women are involuntarily exposed to environmental tobacco smoke (ETS). Polish women had slightly higher exposure levels than German women, with overall means of 9.93 and 8.65 ng cotinine/mg creatinine, respectively. Smoking by the husband was the major source of exposure in both study groups. In the Polish group, the work place was also an important source of ETS exposure. The validity of self-reported passive smoking exposure was found to be generally good; it was somewhat better in the German study group. A negative attitude toward tobacco smoke was slightly stronger among the German women. The percentage of women misreporting their active smoking status was low. PMID- 1420517 TI - Hospitalization with vertebral fracture among the aged: a national population based study, 1986-1989. AB - Whereas fractures related to osteoporosis have become a pressing public health concern, relatively few epidemiologic studies have focused on vertebral fractures. To shed further light on the occurrence of this injury, we collected data from the Health Care Financing Administration on 151,986 discharges listing a diagnosis of vertebral fracture over a 4-year period. After adjusting for age, white women experienced the highest rates of discharge, at 17.1 per 10,000 per year, followed by white men (9.9 per 10,000), black women (3.7 per 10,000), and black men (2.5 per 10,000). Among white women, discharge rates rose exponentially from 5.3 discharges per 10,000 population at age 65 to nearly 47.8 per 10,000 at age 90. White men, black women, and black men experienced less dramatic age related increases in discharge rates. The similarity of these patterns to discharge rates for hip fracture suggests that the race-sex differences in vertebral fracture discharge rates may be due to differences in the incidence of vertebral fracture. PMID- 1420518 TI - A case-control study of smoking and gallbladder disease: importance of examining time relations. AB - We report a case-control study of gallbladder disease and cigarette smoking. Subjects were 252 incident cases and 233 age-sex-residence-matched community controls. Three quarters of the subjects were women. The age-matched risk of gallbladder disease was increased in current smokers vs never-smokers [odds ratio (OR) = 1.6 and 1.3 in women and men, respectively] and in past smokers (OR = 1.5 for each sex). In light of earlier research, showing that, in women, certain risk factors for gallbladder disease may act maximally soon after first exposure, we examined time relations. In women, multivariable analysis showed that the risk increase was especially high in current-smoking women less than 35 years of age [OR = 3.5, 95% confidence interval (CI) = 1.2-9.8] and in women who had been smoking for 1-8 years (OR = 2.8, 95% CI = 1.1-7.1). These results indicate that, in women, the smoking-related risk of gallbladder disease is greatest soon after first exposure--as has also been reported for oral contraceptive use. The findings highlight the potential for mis-estimating risk in case-control studies when late-occurring cases have a different relation to the exposure factor than do the early-occurring cases within the original, albeit undocumented, exposure cohort. PMID- 1420519 TI - Mammary gland mass and breast cancer risk. AB - Evidence indicates that early life events and conditions, possibly extending to the intrauterine stages of life, and including energy restriction in early life, affect the risk of breast cancer. The mechanism of this effect is likely to be through a reduction in mammary gland mass and, inferentially, the total number of ductal stem cells. The evidence derives from epidemiologic and animal studies. It can explain certain epidemiologic findings that cannot be accounted for by more established breast cancer risk factors, including the more frequent occurrence of breast cancer in the left breast and the higher incidence of this disease among caucasian women than among Asian women in Asia. PMID- 1420521 TI - Reliability of sexual behavior data among high school students in Rome. AB - We compared findings on sexual behavior from a self-administered questionnaire and a face-to-face interview, separated by 2-4 weeks, directed at 383 Italian secondary school students. The correlation coefficients or kappa values for reported prevalence of coital experience, age at first intercourse, and age of first partner were all greater than 0.7. The interview underreported coitus and overreported condom use, when administered before the questionnaire. The students thought that 18.4% of their classmates had ever had coitus, compared with 23.5% on self-report. We conclude that despite an overall high reproducibility of sexual behavior measures, distortions due to perceptions of social desirability might occur. PMID- 1420520 TI - Lactation history and bone mineral density among perimenopausal women. AB - To examine the relation between lactation and bone mineral density, we conducted a cross-sectional study among white, nonsmoking, perimenopausal women age 40-54. Three hundred fifty-two women completed a questionnaire covering medical and reproductive histories, physical activity, and diet. We measured the bone density of lumbar vertebrae 2-4 with dual photon absorptiometry, and the midradius and distal radius with single photon absorptiometry. Women with a history of lactation had 41 mg per cm2 higher lumbar bone mineral density than women with no lactation (95% confidence interval = 8-74 mg per cm2), controlling for parity, body mass, physical activity, and menopausal status. We found no important increase at mid- or distal radius. PMID- 1420522 TI - The reliability of self-reported alcohol consumption in the remote past. AB - We examined the reliability of self-reported alcohol consumption in past age periods of women's lives. As part of a case-control study of breast cancer conducted in Massachusetts and Wisconsin in 1988-1991, the same questionnaire was administered for a second time to 211 controls (mean age = 54 years) after an interval of 6-12 months. The Spearman correlation coefficients between the average number of grams of alcohol consumed daily reported in the two interviews, by age period of consumption, were: 16-19 years, r = 0.81; 20-29 years, r = 0.84; 30-39 years, r = 0.75; and for recent consumption, r = 0.77. Self-reported alcohol consumption throughout adult life was reported with precision sufficient to make the ranking of subjects' intake consistent between interviews. PMID- 1420523 TI - Fletcher's paradox. PMID- 1420524 TI - The paradigms of wound care. PMID- 1420525 TI - Wound care: everybody's doing it, but is that enough? PMID- 1420526 TI - Done at last! PMID- 1420527 TI - A research-based risk assessment tool as the cornerstone of a pressure ulcer prevention program. AB - By highlighting theories of knowledge utilization, we consider some of the factors and issues in planning research utilization projects. By our use of a research utilization model in developing a research-based pressure ulcer prevention program, we help to bridge the gap between research and practice. PMID- 1420528 TI - Clinical trial of the Braden Scale on an acute care medical unit. AB - Pressure ulcers in hospitalized patients represent a significant challenge to the health professionals who care for these patients. This challenge extends to the health care system as a whole because of the staggering costs associated with pressure ulcer resolution. Although the relative benefits of various treatment methods have long been debated, intervention before ulcer formation clearly stands as the most efficacious approach to this problem. The Braden Scale for Predicting Pressure Sore Risk, a recently developed paper tool, was evaluated in our acute care medical unit for its ability to predict pressure ulcer occurrence. The sensitivity of the Braden Scale in this evaluation was much lower than that reported in other published studies. The Braden Scale was less effective than the nurse judgment prediction method, the current prevailing prediction method at this institution. The gravity of these results, however, is unclear because of the questionable incidence of ulcers in this study, which may be artificially high due to permissive criteria used in the identification of stage 1 ulcers. We determined that the lack of unequivocally defined criteria for the identification of stage 1 ulcers may contribute to variance between studies. We also found that intervention measures were used only 27% of the time after the identification of patients at risk. PMID- 1420529 TI - Fibronectin in acute and chronic wounds. AB - Fibronectin, a fibrillar glycoprotein, is the major adhesive protein deposited at the wound interface during acute wound healing. Its abilities to interact with both cells and matrix are responsible for its description and characterization as a multifunctional adhesive glycoprotein. Fibronectin functions to promote cell adhesion, cell shape and spreading, organization of the cytoskeleton, hemostasis and thrombosis, cell migration, and phagocytosis. Both in vitro and in vivo studies indicate that fibronectin interacts with cells important to wound healing, including platelets, neutrophils, monocytes, fibroblasts, endothelial cells, and epidermal cells. It promotes adhesion between cells and between cell and matrix, cell spreading, migration, chemotaxis, phagocytosis, and matrix and basement membrane organization. Fibronectin is consequently active during each stage of wound healing. Its importance in acute wound healing is now widely recognized. More recently, investigators have begun to study fibronectin's role in chronic wounds. This article briefly reviews fibronectin, outlines its role in wound healing, and discusses current research on fibronectin in chronic wounds. PMID- 1420530 TI - Air support therapy: ethical considerations. AB - Pressure ulcers are a major health problem for the elderly population in the United States. Billion of health care dollars are spent for hospitalization, air support therapy, wound care products, and nursing care. In addition, the cost in human suffering is priceless. Many patients with pressure ulcers have several chronic diseases that make wound healing difficult. Nurses must begin to examine the ethical principles that guide their care of these patients. This article focuses on some ethical issues related to the care of patients with pressure ulcers and the difficulties encountered with pressure ulcer care. Careful analysis of the goals of pressure ulcer treatment may help nurses develop ethical guidelines to direct them in the care of these patients. PMID- 1420531 TI - Options in practice: transverse loop colostomy in midline incision. Descending loop colostomy over a Hollister bridge. PMID- 1420533 TI - Ostomy care. PMID- 1420532 TI - Pressure ulcers in adults: prediction and prevention. Agency for Health Care Policy and Research. PMID- 1420534 TI - More on bowel and bladder management in a child. PMID- 1420535 TI - Oxybutynin dosage questioned. PMID- 1420536 TI - Trends in Indian adolescent drug and alcohol use. AB - Trends in overall drug use among Indian and non-Indian youth have followed similar patterns, increasing from 1975 to the early 1980s and, for the most-used drugs, declining since then. At every point in time more reservation Indian youth are involved with drugs than are non-Indian youth. Rates for cocaine and hallucinogen use by Indian youth increase until 1990. The decline in overall drug use has occurred because a considerable number of moderate users have shifted to non-use. There has been no decrease in the proportion of high-risk users; since 1980, it has stayed between 17% and 20%. Societal changes and prevention programs are reaching casual drug users but not those susceptible to heavy drug involvement. PMID- 1420537 TI - Comparison of drug use rates for reservation Indian, non-reservation Indian and Anglo youth. AB - Rates of drug use and involvement were compared for three groups: Indian youth living on reservations, Indian youth living off reservations and Anglo youth. A consistent pattern emerged, showing the lowest rates of use among Anglo youth, higher rates among non-reservation Indian youth, and the highest rates among Indian youth on reservations. Rates of tobacco use, both smoked and smokeless, and marijuana use are especially high for Indian youth. Indian youth also show a pattern of earlier initiation to drug use. Gender differences reveal slightly higher rates of use for males, although the differences are not great enough to suggest that prevention efforts for males should have a higher priority. PMID- 1420538 TI - The consequences of drug and alcohol use for Indian youth. AB - Indian youth have higher rates of using alcohol and drugs in ways that increase their risk--getting very drunk, drinking while driving, and using drugs and alcohol together. The highest rate is found among reservation youth, a lower rate among non-reservation Indians, and the lowest rate among non-Indian youth. Frequency of self-reported consequences from alcohol and drug use follow the same order, with 15% of reservation seniors involved in an alcohol-related accident. The most frequent consequences involve relationship problems. Drug injection is rare in all groups. PMID- 1420540 TI - Drug use of friends: a comparison of reservation and non-reservation Indian youth. AB - There is not much drug use at school, but reservation youth are most likely, non reservation Indian youth next most likely, and non-Indian youth least likely to have used drugs at school. Alcohol and drugs are used most frequently at weekend parties and at night with friends. Reservation youth are twice as likely as the others to have used alcohol while driving around and three times more likely to have used drugs while driving around. Drugs are used with friends. Heavy drug users are more likely to have friends who use drugs and friends who encourage drug use and are less likely to have friends who would try to stop them from using drugs. PMID- 1420539 TI - Attitudes about drugs and the drug use of Indian youth. AB - Alcohol, marijuana, and inhalants are the easiest drugs to obtain, but all drugs are available to some students. Younger students felt that inhalants were easier to get than marijuana. Availability does not have a major effect on use; if there is motivation to use, drugs are available. Perceived harm is linked to use, and 8th-grade reservation youth show the lowest belief that drugs are harmful; only 51% believe that using marijuana regularly will lead to "a lot" of harm. In general, non-Indian youth show higher rates of perceived harm, congruent with their lower rates of drug use. PMID- 1420541 TI - Characteristics of Indian youth and drug use. AB - The overall high rates of drug use found among Indian youth may be accounted for in part by lack of educational and employment opportunity and other endemic problems of Indian reservations. Individual drug involvement is most highly related to membership in drug-using peer clusters; but because of physical isolation, links between drug use and close friends are weaker for Indian youth, and family influence is felt more strongly. Anxiety, depression, and low self esteem are not related to drug involvement, but angry youth are more likely to have drug-involved peers. Risk factors for Indian youth are low family caring, age first drunk, poor school adjustment, weak family sanctions against drugs, positive attitudes toward alcohol use, risk of school dropout, father not at home, and poor religious identification. PMID- 1420542 TI - An annotated bibliography of papers on drug abuse among Indian youth by staff of the Tri-Ethnic Center for Prevention Research. PMID- 1420543 TI - Beyond boundaries: cross-cultural care. PMID- 1420544 TI - Managing the distressed newborn. PMID- 1420546 TI - Eating your way to a healthy lifestyle. PMID- 1420545 TI - Eating your life away. PMID- 1420547 TI - Dying at home. PMID- 1420548 TI - Deal the public in. PMID- 1420549 TI - Enzyme histochemistry of the olfactory and vomeronasal sensory epithelia in the golden hamster. AB - Histochemical activities of several enzymes were investigated in the olfactory epithelium (OE) and vomeronasal organ (VNO) of the golden hamster. Activities of adenosine triphosphatase, lactate dehydrogenase and succinate dehydrogenase were intense in the OE, and the sensory (VSE) and respiratory epithelium (VRE) of the VNO. The activity of acid phosphatase was intense in both the OE and the VSE, while that of non-specific esterase was intense in the VSE alone. The activity of alkaline phosphatase was detectable only in the VRE. Activities of monoamine oxidase and acetylcholine esterase were negative in all of the OE, VSE and VRE. These similarities and differences in the histochemical distribution of enzymes between OE and VSE may reflect the common olfactory function and/or functional specialization in these epithelia. On the other hand, the VRE was considerably different from the OE and VSE in the enzymatic distribution. This may reflect the non-olfactory function of this epithelium. PMID- 1420550 TI - Effects of pulsing electromagnetic fields on the ligament healing in rabbits. AB - Effects of pulsing electromagnetic fields (PEMFs) on ligament healing were investigated using 80 rabbits. All animals received square resection (4 mm x 4 mm) of both patellar ligaments in full thickness at their center. They were divided into 4 groups of 20 rabbits each and stimulated with different electromagnetic intensity of 0 (control), 2, 10, and 50 gauss (G) for 6 hr daily. Pulse frequency and pulse width were 10 Hz and 25 microseconds, respectively. After PEMFs stimulations for 1, 2, 3 and 4 weeks, 5 animals of each group were euthanized and the regenerated tissue at the defective portion was investigated histologically and biomechanically. Histologically, the tissue stimulated by PEMFs showed an earlier increase in capillaries and fibroblasts and more matured, prominent longitudinal orientation of collagen fibers than those of control groups. Among the rabbits stimulated electromagnetically, those stimulated at 50 G revealed the earliest ligament healing. Tensile strength of regenerated ligament tissues of any PEMFs groups increased significantly at 1 and 2 weeks after operation, however, at 3 and 4 weeks after operation, there were no significant differences between groups. Among these values, those of 50 G group were the highest consistently during most of the experimental period. From the above results, PEMFs enhanced the earlier stage of ligament healings and 50 G gauss seemed to be the most effective among the 3 field intensities used. This promoting effect may potentiate the earlier recovery of the function after the ligament injury. PMID- 1420551 TI - Production and some properties of cytotoxins produced by Campylobacter species isolated from proliferative enteropathy in swine. AB - Cytotoxin production by Campylobacter species isolated from proliferative enteropathy in swine was examined. Twenty-one of 29 strains of C. hyointestinalis, 10 of 27 strains of C. mucosalis and 10 of 10 strains of C. coli were cytotoxin positive. By the gel filtration chromatography of C. hyointestinalis culture filtrate, cytotoxin activities were observed in two peaks (fraction I and fraction II). Most of the cytotoxic activities lay in fraction I, which is heat-labile, trypsin-sensitive and the molecular weight was estimated at 40,000. On the other hand, fraction II cytotoxin was heat-stable, trypsin insusceptible and molecular weight was approximately 1,000. PMID- 1420552 TI - Histochemical studies on the dependence of secretory function of the major vestibular gland (Bartholin's gland) on ovarian steroid hormones in the cat. AB - The dependency of the secretory function of the feline major vestibular gland (Bartholin's gland) on the ovarian steroid hormones was studied histochemically. After estrogen (estradiol-17 beta or diethylstilbestrol), progesterone or a combination of these was administered to cats which were previously ovariohysterectomized, the major vestibular glands were removed, embedded in paraffin, sectioned, and stained by alcian blue, periodic acid-Schiff or peroxidase-labeled lectin (peanut agglutinin and wheat germ agglutinin). The vividly positive reactions to the stainings applied were observed in the secretory epithelial cells of the major vestibular glands in the estrogen treated animals. The dependency of the secretory function of the major vestibular glands on the estrogen was demonstrated in this study. PMID- 1420553 TI - Evaluation of the anaerobic method for the analysis of fecal microflora of beagle dogs. AB - The plate-in-bottle method of Mitsuoka et al. (1969) for the counting of fecal bacteria in beagle dogs was superior to an anaerobic jar method. Comparisons of three nonselective media, such as medium 10 supplemented with 10% cecal extract of dogs (designated as M10C), M10 with 10% fecal extract of dogs (M10F), and M10, by the plate-in-bottle method indicated that the visible bacterial counts for M10C were higher than those for M10 and M10F. The high percentage (18.4%) of numbers of the extremely oxygen-sensitive anaerobes to the fecal total counts by using the plate-in-bottle method with M10C was also observed. PMID- 1420554 TI - In vitro study on the increase of trypsin resistance in the rat testicular sperm head. AB - The alteration of trypsin resistance in rat sperm head was investigated after the sperm were incubated in the culture media (199-Earele, 1% BSA) containing the inhibitors of protein synthesis. The head of non-incubated testicular sperm was easily digested by trypsin (1 mg/ml) while the head of the incubated sperm showed resistance to trypsin digestion after 3 hr-incubation. Trypsin resistance in epididymal sperm head did not change after the sperm was incubated. Neither cycloheximide (100 micrograms/ml) nor chloramphenicol (100 micrograms/ml) affected the trypsin resistance in the testicular sperm head. PMID- 1420555 TI - Activities of certain cytoplasmic enzymes in bovine T lymphoma. AB - Activities of certain cytoplasmic enzymes were measured in bovine T lymphoma (BTL PC3 cells). The activities of hexokinase, pyruvate kinase and glucose-6-phosphate dehydrogenase in PC3 cells were elevated as much as 2 or 3-fold of those in bovine thymocyte. The high activities of these enzymes derived from activation of glucose metabolism may reflect the high growth potential of PC3 cells. PMID- 1420556 TI - Effect of cobra venom factor on experimental infection of mice against Clostridium chauvoei. AB - The effect of cobra venom factor (CoVF) treatment was examined to clarify the mechanism of resistance of mice to Clostridium chauvoei infection. In CoVF treated mice inoculated with spores of C. chauvoei, no death occurred and the organisms in the infected muscle progressively decreased, similar to that of non treated control mice. These results indicated that C3 did not play a significant role in the resistance of mice against C. chauvoei infection. PMID- 1420557 TI - Surgery of hepatic cysts in a cat. AB - A 2-year-old female Japanese domestic cat weighing 3.6 kg was presented due to marked abdominal distention and was diagnosed as hepatic cyst. The bile acid concentration of the hepatic cyst was as low as the serum bile acid concentration. The membrane of the cysts was excised from the edge of the compressed hepatic tissue and no other surgical manipulation was performed. This surgical procedure is simple and quick compared to hepatic lobectomy, however, it is necessary to evaluate the fluid of the cyst before performing this procedure. PMID- 1420558 TI - Enhanced resistance to bacterial infections in mice by oral administration of an active egg white product. AB - We found that the oral administration of active egg white product (AEWP) enhances host resistance to infections. The prophylactic administration of AEWP enhanced nonspecific resistance in mice to systemic infection with E. coli. Moreover, the therapeutic administration of AEWP was effective against S. aureus infection in mice. PMID- 1420559 TI - Comparison of the inhibitory effect of sulfamonomethoxine and other sulfonamides on capsule formation of Bordetella bronchiseptica. AB - The inhibitory effect of sulfamonomethoxine and other sulfonamides on the capsule formation of sulfonamide-resistant Bordetella bronchiseptica was investigated. All the sulfonamides having MeO(-OCH3) groups inhibited the capsule formation of B. bronchiseptica. Strong inhibition was obtained with sulfamonomethoxine. Inhibition was not seen with sulfonamides having no MeO groups. PMID- 1420560 TI - Visual evoked potentials in guinea pigs with brain lesion. AB - Visual evoked potentials (VEPs) were recorded in 10 adult male guinea pigs with brain lesion. Lesions were produced in 5 animals by superficial suction of the occipital lobe. The other 5 animals were orally administered with hexachlorophene (about 35 mg/kg/day) for 28 days. In the VEP following the ablation of the occipital lobe, the peaks P10, N20, P55, N75, N140 and P200 disappeared in many cases. The amplitude of the peak N40 decreased to approximately one half its control VEP. In the VEP obtained from the animals administered with hexachlorophene, the peak latencies of N20, P30, P55, N75 and P100 were slightly prolonged after the 7th day following the first administration. On the other hand, there was no change in the latency of N40 during the whole period of administration. The peak-to-peak amplitude showed some variability in different peaks. Histologically, diffuse status spongiosis were found in the white matter of the cerebrum, cerebellum, and brain stem. As described above, the ablation of the occipital lobe caused markedly depressed VEPs, however, the responses to the photic stimulation persisted after the injury. On the other hand, the VEPs of animals administered with hexachlorophene showed a high probability of peak appearance, and a decrease in amplitude was not marked. PMID- 1420561 TI - Comparison of antimicrobial resistant Escherichia coli in wild and captive Japanese serows. AB - The fecal Escherichia coli isolated from wild Japanese serows living in mountainous areas away from humans and those from captive serows kept in human areas were examined for antimicrobial resistance and the possession of transferable R plasmids. Of 874 E. coli strains isolated from 283 wild serows in 1980-1981, only 11 (1.3%) were resistant to at least one of 6 antimicrobial drugs; ampicillin, streptomycin, tetracycline, chloramphenicol, kanamycin and sulfadimethoxin. Seven (2.5%) individuals were found to carry resistant E. coli. To heighten the isolation frequency of drug-resistant strains, fecal samples of 244 wild serows in 1983-1984 were cultured directly onto drug-supplemented media. Only 12 (4.9%) serows were shown to have drug-resistant E. coli. No transferable R plasmid was detected among a total of 87 resistant strains from wild serows. In contrast, all 33 captive serows except one which was kept only one day after capture, showed resistant E. coli and 20 (60.6%) serows were excreting R plasmid carrying E. coli. Of 161 drug-resistant strains from captive serows, 50 (31.1%) were found to carry R plasmids. Wild serows seemed to readily change to harbor resistant E. coli almost as soon they were reared in human areas without direct exposure to drugs. These results lead to the conclusion that drug-resistant E. coli can probably be used as microbial indicator for natural environmental pollution. PMID- 1420562 TI - Anatomically corrected malposition (ACM) with subpulmonary infundibulum in a calf: clinico-morphologic case report. AB - A Japanese black calf with cyanosis, tachycardia, tachypnea and systolic murmur died of hypoxemia and cardiac insufficiency on the 38th day after birth. We could not establish the diagnosis during it's life. However, anatomically corrected malposition (ACM) with ventricular septal defect was confirmed at autopsy. There was situs solitus of the viscera and atria with atrio-ventricular discordance and ventriculo-arterial concordance. The ventricles demonstrated l-loop, i.e. on the right-sided ventricle there was a markedly enlarged morphologic left ventricle, and on the left-sided ventricle there was a hypoplastic morphologic right ventricle with a stenotic tricuspid valve and Ebstein-like deformity. The right posterior aorta originated from the left ventricle. The pulmonary artery arose from the left-sided right ventricle via infundibulum. There was a fibrous continuity between the aortic and mitral valve. We considered that this is the first reported case of bovine ACM. PMID- 1420563 TI - The role of 36 megadalton plasmid of Salmonella enteritidis for the pathogenesis in mice. AB - The pathogenesis associated with the 36 Megadalton (Md) plasmid of Salmonella choleraesuis subsp. choleraesuis serovar Enteritidis (S. Enteritidis) was assessed by using the plasmid-containing strain AL1190, plasmid-cured strain AL1192, and plasmid-reintroduced strain AL1193. After oral inoculation of strain AL1190 or AL1192 to C57BL/6 mice, mesenteric lymph nodes, spleens, and livers were examined for the numbers of viable bacteria and for the histopathological changes. The numbers of bacteria were greater and histopathological changes were severer in these organs of mice inoculated with strain AL1190, than in those with strain AL1192. Strains AL1190, AL1192, and AL1193 showed the equivalent survival rate to sera of guinea pig, calf, and pig, and grew equally well under the iron limiting conditions. These results suggested that the 36 Md plasmid of S. Enteritidis contribute to the spread of the infection beyond small intestines to mesenteric lymph nodes, spleens, and livers, but not to serum resistance or acquisition of iron. PMID- 1420564 TI - Chemotactic activity of hemocytes derived from a brackish-water clam, Corbicula japonica, to Vibrio parahaemolyticus and Escherichia coli strains. AB - Hemocytes from adult and juvenile specimens of a brackish-water clam, Corbicula japonica, were attracted chemotactically to live cells of Vibrio parahaemolyticus and Escherichia coli strains in a balanced salt solution, which was enhanced significantly in the presence of respective C. japonica plasma. Chemotactic attractions of adult's and juvenile's hemocytes were seen also in artificial seawater at a similar level to those in the balanced salt solution. Chemotactic attractions of juvenile's hemocytes to these strains were lower in level than those of adult's hemocytes. C. japonica plasma seems to facilitate for C. japonica hemocytes to recognize these organisms. PMID- 1420565 TI - Immunohistochemical findings of juxtaglomerular cells on acute phase in two kidney Goldblatt hypertensive rats and spontaneously hypertensive rats. AB - Juxtaglomerular (JG) cells on the acute phase in two-kidney Goldblatt hypertensive (2KGH) rats and spontaneously hypertensive rats (SHR) were examined immunohistochemically. JG cells in 2KGH rats and SHR were positively stained with anti-renin serum and anti-angiotensin II (A II) serum. In 2KGH rats, the number of renin and AII immunoreactive JG cells in the clipped kidneys increased throughout the observation period. The number of renin and AII immunoreactive JG cells in the unclipped kidneys was almost the same as that in control rats, although immunoreactivity of these cells was weak and they were small in size. These changes in the unclipped kidneys became obvious with the time course after operation. We did not see any changes in these cells in SHR. In 2KGH rats treated with captopril, the number of renin immunoreactive JG cells in the clipped kidneys increased, whereas that of AII immunoreactive JG cells in the bilateral kidney decreased. When captopril was administered to SHR, the number of renin immunoreactive JG cells in the bilateral kidney increased, whereas that of AII immunoreactive JG cells in the bilateral kidney decreased. These results suggested that the JG cell in the bilateral kidney was closely related to the development of hypertension in 2KGH rats, but not in SHR. The increase of renin immunoreactive JG cells in 2KGH rats and SHR treated with captopril was probably due to the removal of negative feedback inhibition of AII on JG cells. PMID- 1420566 TI - Monoclonal antibodies to feline lymphocyte membranes recognize the leukocyte common antigen (CD45R). AB - By immunization of BALB/c mice with a feline T lymphoblastoid cell line, MYA-1 cells, two types of lymphocyte-specific monoclonal antibodies (mAbs) were obtained. The 220/205/190 kd protein defined by 2F11 mAb is highly expressed on the surface of MYA-1 cells and another feline T lymphoma cell line, FL74 cells. The protein is also expressed on normal feline thymocytes, splenocytes and feline peripheral blood mononuclear cells (PBMCs). Another mAb, 17B10, caused similar results as those of 2F11 except for its low reactivity with FL74 cells. The second type of mAb, 15B3, defined the 220 kd protein. The reactivities of this mAb with MYA-1 cells, FL74 cells, PBMCs and feline splenocytes were lower than the former two mAbs, and did not react to feline thymocytes. On the other hand, 17B10 and 15B3 defined partial populations of MYA-1 and FL74 cells recognized by 2F11. The cells defined by the 2F11 and 17B10 are all leukocytes in spleen and lymph node. In contrast, 15B3 defined most of the cells in B cell area and partially in T cell area. These results suggested that 2F11 and 17B10 recognized the specific antigen of 220/205/190 kd of the leukocyte-common antigen (L-CA) family, CD45R, with different epitopes, and that 15B3 defined the distinct antigen of 220 kd on CD45R. PMID- 1420567 TI - Clinicopathology of meningoventriculitis due to Streptococcus bovis infection in neonatal calves. AB - Three neonatal calves ranging in age from 4 to 14 days were examined pathologically and bacteriologically. The calves showed depression, anorexia, pyrexia, and difficulty or inability to stand followed by cloudiness of the ocular aqueous humor or cornea. Autopsy revealed congestion, petechiae, and cloudy areas in the meninges. Histologically, the central nervous system (CNS) lesions were prominent and limited to the meninges where fibrinous exudate and infiltrations of neutrophils, macrophages, and lymphocytes were present. There were mild or slight degrees of choroid plexitis and ependymitis. Endophthalmitis was seen as a concurrent lesion in all cases. Fibrinous or fibrinopurulent changes were found in the peritoneum and epicardium as well as in several other organs. Numerous Gram-positive cocci were detected in affected areas of the whole body. Bacteriologically, Streptococcus bovis was isolated from all examined materials consisting of the brain, cerebrospinal fluid, ocular aqueous humor, and several other organs. These results suggest that the lesions were associated with infection of the organism and that the present cases were in the process of septicemia. PMID- 1420568 TI - Non-specific natural cytotoxic factor released from bovine peripheral blood lymphocytes. AB - Natural cytotoxicity against bovine leukemia cells (PC-3 cells) was found in bovine peripheral blood lymphocytes (PBL), and in non-adherent cells but not in adherent cells to nylon-wool column. Natural cytotoxic cells (NCC), which have natural cytotoxic activity, are found in T cell-rich fraction. When NCC were cocultured with PC-3 cells, natural cytotoxic factor (NCF) was released rapidly from NCC, and dose-response curve for NCF was almost linear induction. Cytotoxicity against PC-3 cells by NCC or NCF was increased with an increment of incubation period. Cytotoxicity against K562 cells, CL-1 cells, M1 cells or EL-4 cells by NCF was almost the same level as that against PC-3 cells, but that against those cell lines by NCC was not found. NCF activity in culture fluid from NCC cocultured with K562 cells or CL-1 cells was lower than that from NCC cocultured with PC-3 cells. PMID- 1420569 TI - Immunocytochemical and morphometric studies on the effects of dehydration on vasopressin-secreting cells in the hypothalamus of the Mongolian gerbils. AB - Effects of dehydration on vasopressin-secreting cells (VP cells) of the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) in the Mongolian gerbils were studied immunocytochemically and morphometrically. The plasma osmolality was measured at the time of sacrifice of individual animals and the body weight was measured every day during dehydration. The plasma osmolality increased significantly on day 3 of dehydration, followed by a gradual increase to reach nearly its equibilium state on day 10. The body weight decreased rapidly until day 10, followed by a gradual decrease thereafter. The area of VP cells increased significantly in both the SON and PVN on day 1 of dehydration, the level being nearly the same until days 3 to 5 and going up on day 7 to reach the plateau after day 15. These findings seem to reflect a compensation mechanism between the volume of body fluid and the plasma osmolality and to reflect responses of VP cells to the osmotic stimuli. Electron microscopic observation revealed that, at the beginning and late stages of dehydration, the increase in the area of VP cells was in parallel with the expansion of the Golgi area and with the distension of cisternae of the rough endoplasmic reticulum. PMID- 1420570 TI - Experimental Tonsillophilus suis granuloma in rats and guinea pigs. AB - Rats and guinea pigs were experimentally infected by intradermal and intraperitoneal inoculation of T. suis. These animals were observed for pathologic changes at various stages. Macroscopic observation disclosed visible grayish white soft nodules at the injection site in those inoculated intradermally and many grayish white nodules in the peritoneum of those inoculated intraperitoneally. Histopathological examination revealed the presence of characteristic microbial elements in the centre of the lesions. Various stages of the lesions were recognized; the early stage being abscess, the advanced stage being pus-forming granuloma and the final stage being residual granuloma. The microbial elements were composed of spores, thalli and multilocular tubers. Clubs were formed around microbial elements in rats inoculated intradermally and in guinea pigs inoculated intraperitoneally. The characteristic T. suis lesions in pigs were reproduced by experimental infection of this organisms in rats and guinea pigs, and thus the pathogenicity of T. suis was confirmed. PMID- 1420571 TI - Relationship between pulmonary arterial pressure and pulmonary thromboembolism associated with dead worms in canine heartworm disease. AB - To examine effects of thromboemboli due to dead worms on pulmonary arterial pressure (PAP), 20 to 50 dead heartworms were inserted into the pulmonary arteries of 4 heartworm uninfected dogs (uninfected group) and 11 dogs infected with heartworms (infected group). In the uninfected group, the mean PAP rose 1 week after worm insertion (10.9 to 166. mmHg), but it recovered by the 4th week. Clinical signs, hemodynamics and blood gas findings also deteriorated at the 1st week, but recovered at the 4th week. Angiographic and pathological findings indicated that blood flow recovered through the spaces between thromboemboli and vessel walls at the 4th week. The infected dogs were divided into three groups. In the infected-I group (5 dogs), the intimal lesions of the pulmonary arteries were slight, and clinical and laboratory findings showed changes similar to those of the uninfected group. In the infected-II group (4 dogs), the pulmonary arterial lesions were severe and the mean PAP was higher (25.7 mmHg) than in the uninfected group before worm insertion. An increase in PAP (34.1 mmHg) and worsening of clinical and laboratory findings were noticed till the 4th week. Thromboemboli adhered extensively to the vessel walls. Two dogs in the infected III group died of severe dyspnea on the 9th and 10th day, and the mean PAP rose remarkably at the 1st week (from 19.4 to 28.2 mmHg). Severe pulmonary parenchymal lesions with edema or perforation were observed. From the above results, it was clarified that effects of dead worms on PAP and clinical signs depended on the severity of pulmonary arterial lesions before worm insertion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420572 TI - The complete amino acid sequence of the Clostridium botulinum type D neurotoxin, deduced by nucleotide sequence analysis of the encoding phage d-16 phi genome. AB - The complete nucleotide sequence of Clostridium botulinum type D strain CB16 neurotoxin was determined and the deduced amino acid sequence is reported here for the first time. The structure and function of botulinum type D neurotoxin is discussed from a molecular biological viewpoint. DNA was extracted from toxin converting phage d-16 phi of C. botulinum type D strain CB16, and a fragment (about 10 kbp) coding for the neurotoxin was cloned into Escherichia coli using lambda gt11. A 21-mer oligonucleotide which corresponds to Phe7 to Val13 of the partial amino acid sequence near the N-terminus of the type D neurotoxin was synthesized and used as a probe to identify the gene encoding type D neurotoxin. The nucleotide sequence contained a single open reading frame coding for 1,275 amino acids (molecular weight of 146,785) and the deduced amino acid sequence corresponded exactly to the partial amino acid sequences determined by direct microsequencing of the neurotoxin fragments. In the dichain molecule of the neurotoxin, Thr2 and Asn443 formed the N-termini of the light chain (M.W. 50,410) and heavy chain (M.W. 96,394) respectively, and these two chains were linked with a disulfide bond between Cys437 on the light chain and Cys450 on the heavy chain. The nucleotide sequence of the D-CB16 neurotoxin differed from that previously reported for type D neurotoxin by three nucleotides. PMID- 1420573 TI - Overshoot and high equilibrium in body temperature responses of rats to ambient heat: relation to thermoregulatory ability and improvement in estimation of survival time in a hot environment. AB - Physiological significance of body temperature responses to ambient heat (BTRAH) with high overshoot or a high equilibrium phase was studied in relation to thermoregulatory ability. Subsequently, an attempt was made to predict survival time (ST) by measuring the period required to attain a colonic temperature (Tco) of 42.0 degrees C (t42.0), whereas ST hitherto having been calculated on the basis of a period until Tco attains 42.5 degrees C (t42.5). Tco of rat was monitored continuously with a Cu-Co thermocouple during exposure to an ambient temperature (Ta) of 42.5 degrees C. The lower the overshoot temperature (Tos) or the equilibrium temperature (Teq), the longer the rats survived in a hot environment. The present findings further suggest that these two types of BTRAH are immature variations of the typical triphasic BTRAH which is characteristic of heat resistant individuals. A new regression line of ST (Y) as a function of the t42.0 (X) was obtained for most rats as follows: Y = 0.963X + 43.85 (male); and Y = 0.973X + 39.10 (female). This equation enabled to calculate ST without thermal death. However, the former approach based on t42.5 must be applied yet in small number of rats which showed the irregular BTRAHs with Tos or Teq higher than 42.0 degrees C. Delayed influence on survival and fecundity at a Ta of 24 degrees C were not found during one year following this hyperthermia up to 42.5 degrees C. PMID- 1420574 TI - Theoretical epidemiology on bovine ephemeral fever outbreaks in Tanegashima Island, Kagoshima Prefecture of Japan in 1988. AB - From the end of September to November 1988, a compact scale of bovine ephemeral fever (BEF) outbreaks occurred suddenly in Tanegashima island of Kagoshima Prefecture, southern part of Kyusyu island of Japan. The BEF outbreak pattern showed epidemical characteristics as follows; (1) outbreak spread from few foci to zone during one month, and (2) the disease might be transmitted in farms with a fixed probability of adequate contact. By using the above aspects, we attempted to analyze the disease theoretically with the application of Poisson distribution and Reed-Frost model. The BEF incidence in farms was in well accord with the Poisson distribution. As the very rare event occurred in unit time or in unit area in this epidemic, the cattle population at risk were equivalently susceptible to BEF virus in this island, due to the influence of no vaccination to BEF control before the first outbreak. Similarly, the epidemic curve of the Reed-Frost model was proved to fit well the incidence observed in a farm, and the probability of adequate contact was induced as p = 0.226. If the cattle population is less than 5 in this farm, the outbreak would not occur in the first instance. PMID- 1420575 TI - Detection and characterization of Theileria sergenti proteinases. AB - The lysate of Theileria sergenti piroplasms was tested for proteinases using sodium dodecyl sulfate-polyacrylamide gel electrophoresis in which substrate was included in gel matrix. Six proteinases of molecular weight 330, 125, 98, 94, 67 and 58 kilodalton (kDa) were detected. From the results of the Triton X-114 phase partition, 330, 125 and 58 kDa proteinases were partitioned into aqueous phase, which indicated that they were not associated with parasite membranes. All these three enzymes were classified into metalloproteinase family because of their sensitivities to metal-ion chelating compounds, ethylenediaminetetraacetic acid (EDTA) and 1,10-phenanthroline. On the other hand, 98 and 94 kDa proteinases were membrane-associated metalloproteinases which were preferentially inhibited by 1,10-phenanthroline. Another metalloproteinase of 67 kDa which was inhibited by EDTA and 1,10-phenanthroline was not associated with parasite membranes. Proteinases of 98 and 94 kDa degraded heat-denatured hemoglobin. PMID- 1420576 TI - Pregnancy and lactation affect the microvasculature of the mammary gland in mice. AB - Microvascular changes in the mammary gland in mice during pregnancy and lactation were investigated by scanning electron microscopy (SEM) with a corrosion cast method, transmission electron microscopy (TEM) and morphometry. By SEM, duct associated capillary plexuses were sparsely distributed to branch into adipocytes during virgin period. With advance in pregnancy, both branches from the capillary plexuses and branches from the vessels surrounding adipocytes extended further to form capillary networks. The basket-like architecture was completed by day 18 of pregnancy. These findings may indicate that angiogenesis occurs frequently during this period. During lactation, the basket-like architecture still remained and the capillaries surrounding alveoli meandered. After weaning, the regression of microvasculature followed the degeneration of alveoli. By TEM and morphometry, the density of pinocytotic vesicles (PVs) (number of PVs per microns 2 of endothelium cytoplasm) increased twofold from day 18 of pregnancy to day 5 of lactation, furthermore increased threefold from days 10 to 20 of lactation, and subsequently decreased after weaning. Marginal folds and microvillous processes gradually increased in length with advance in pregnancy, reached the maximum from days 5 to 15 of lactation, and thereafter decreased. In addition, the capillaries with thinner walls were in close contact with alveoli during the late stage of pregnancy and during lactation. Furthermore, the alveolar epithelial cells had well-developed basal infoldings during lactation. These findings suggest that the capillaries play an important role in transporting materials necessary for milk production. PMID- 1420577 TI - Changes in blastogenic responses of lymphocytes and delayed type hypersensitivity responses after vaccination in dogs. AB - To clarify the immunologic effects of vaccination in dogs, we monitored total leukocyte and lymphocyte counts, humoral antibody responses, blastogenic responses of lymphocyte, and delayed type hypersensitivity (DTH) responses after vaccination. Mixed vaccines were administered on day 0 except for canine parvovirus (CPV) vaccine which was readministered on day 21. The puppy and adult dogs had a significant decrease in leukocyte and lymphocyte counts on day 7. The puppies showed a significant increase in the blastogenesis of lymphocytes after each vaccination, whereas the adult dogs had no significant changes. However, the adult dogs were divided into two groups, high responders and low responders in blastogenesis of lymphocytes. The dogs with higher or lower response in SI values on day 0 tended to show decrease or increase after the first vaccination, respectively. Since almost all dogs developed high titers of humoral antibody, it is considered that vaccination acts in an immunomodulative fashion. DTH responses to phytohemagglutinin (PHA) and CPV vaccine monitored at 0, 3, and 8 weeks after the first vaccination produced strong reactions, in particular those to CPV vaccine rose significantly after vaccination and maintained the higher responses for at least 2 months. These results suggest that DTH responses to PHA and CPV vaccine are helpful to monitoring non-specific and specific immune functions in vivo, therefore, DTH could be used as simple and rapid immunologic tests in canine practice. PMID- 1420578 TI - Detection of uremic peaks in dogs by anion exchange high performance liquid chromatography. AB - Sera of dogs with gentamicin-induced uremia were analyzed by high performance liquid chromatography system with strongly basic macroreticular anion exchange resin. Satisfactory separation of peaks was achieved with good reproducibility after deproteinization of sera with trichloroacetic acid at a final concentration of 3%, confirming that the system was suitable for qualitative analysis of uremic serum. The chromatograms showed that the number of peaks and the peak area had relation to concentrations of serum urea nitrogen or creatinine and severity of uremia. Four peaks were selected as suspected canine uremic peaks with high correlation to serum creatinine concentrations which were hardly influenced by extrarenal factors. The results suggested that these four fractions might contain uremic toxins. PMID- 1420579 TI - Field trials on a live bovine respiratory syncytial virus vaccine in calves. AB - Field trials were carried out in calves using a live bovine respiratory syncytial (BRS) virus vaccine prepared from the attenuated BRS virus, strain rs-52. Two hundred seventy-five and 353 calves were vaccinated intranasally and intramuscularly, respectively. No undesirable postvaccinal reactions were observed in the vaccinated calves. Of the serum neutralizing (SN) antibody negative calves 89.7% (26/29) and 92.8% (90/97) developed SN antibody 1 month after intranasal and intramuscular vaccination, respectively. Most of the calves having SN antibody titers of 1:1 or 1:2 at the time of vaccination showed a significant increase in SN antibody titer. About 70% and 90% of the calves vaccinated intranasally and intramuscularly, respectively, maintained SN antibody for 6 months after vaccination. In a field trial, a natural BRS virus infection occurred about 5 months after the start of the trial. Ten of the 16 unvaccinated control calves showed respiratory symptoms due to BRS virus infection. On the contrary, all of the 68 vaccinated calves exhibited no symptoms at all, indicating efficacy of the vaccine. PMID- 1420580 TI - Glomerulopathy with IgA deposition in the dog. AB - In 100 dogs autopsied, glomerular IgA deposition was examined by the immunofluorescence technique and the histopathological features of glomeruli with IgA deposition were examined by light and electron microscopy. The incidence of the IgA deposition was age-related but there were no sex and breed predisposition. Deposition of IgA was observed mainly in mesangial areas in approximately a half (47%) of dogs examined. IgG, IgM and C3 often co-deposited. Histopathology of the glomeruli with IgA deposition indicated increase of mesangial cells, crescent formation, hemispherical deposits in paramesangial areas and glomerular sclerosis. Ultrastructurally electron dense substances positive for IgA deposited in mesangial and paramesangial areas. The examination to know the relation between the severity of IgA deposition and the number of mesangial cells or percent of the cells to total glomerular cells indicated that mesangial cells increased at the early stage of the disease and subsequently epithelial and endothelial cells proliferated as the increasing amount of IgA. Dogs suffering from enteritis or liver diseases showed high incidence of glomerular IgA deposition. PMID- 1420581 TI - Conglutinin, mannan-binding protein, and serum amyloid P component concentrations in sera from cows: changes associated with mastitis. AB - To study the roles of conglutinin (Kg), mannan-binding protein (MBP), and serum amyloid P component (SAP) in the protection of cattle against infections, the concentrations of these proteins in the sera from cows with mastitis were determined by sandwich enzyme-linked immunosorbent assays. The Kg and MBP concentrations in the sera from cows with mastitis were much lower than those from uninfected (or clinically healthy) ones, and increased after recovery. No significant difference in the SAP concentrations was found between healthy and infected cows. With the sera from cows experimentally infected with bovine leukemia virus, the Kg concentrations were also lower than those from uninfected ones, whereas the MBP concentrations were not. From these findings, the Kg concentration is suggested to be serologically a possible indicator for clinical diagnosis of treatment for mastitis although both Kg and MBP concentrations were found to decrease in cows with mastitis and to increase after recovery. PMID- 1420583 TI - Vagal afferent activities and respiratory reflexes during drug-induced bronchoconstriction in the guinea pig. AB - Vagal afferent activities and respiratory reflexes during drug-induced bronchoconstriction were studied in 31 anesthetized, spontaneously breathing or artificially ventilated guinea pigs. Histamine (5, 10, 20 micrograms/kg), ACh (10, 20, 40 micrograms/kg) and endothelin-1 (2 micrograms/kg) were intravenously injected to the animals in order to induce the bronchoconstriction. In spontaneously breathing and vagi intact animals, a considerable respiratory change characterized by rapid-shallow breathing was elicited by histamine. Such respiratory change was abolished by bilateral vagotomy, indicating that the vagal pathway fairly participated in the respiratory change during bronchoconstriction. Indeed, recordings of electrical activities of single vagal afferent nerve fibers from pulmonary stretch and irritant receptors elucidated that the bronchoconstriction by the three drugs markedly influenced these receptor activities. The response of stretch receptors to bronchoconstriction was grouped into four types: two of those types showed a marked increase in their activities and the other two a decrease or no change. Such uneven response was assumed to be derived from heterogenous contraction and aeration among the intrapulmonary small airway. On the other hand, irritant receptors were invariably stimulated by increased transmural pressure during bronchoconstriction. Administration of isoproterenol (20 micrograms/kg) which inhibited the smooth muscle contraction abolished stimulatory effect of the drugs to irritant receptors, suggesting that the effect was due to indirect action through the muscle contraction rather than their direct action to the nerve endings. PMID- 1420582 TI - Impaired baroreflex control of arterial pressure in WHHL rabbits. AB - The present study was designed to investigate baroreflex control capacity of arterial pressure (AP) in the conscious Watanabe heritable hyperlipidemic (WHHL) rabbit. The control capacity of the baroreflex system was assessed with overall open-loop gain (G). Seven WHHL and 14 normal Japanese white rabbits were chronically implanted two catheters in the aortic arch through the left subclavian and common carotid arteries. A small amount of blood (2 ml/kg, body weight) was rapidly extracted into a syringe via the left common carotid artery in the conscious state. Mean arterial pressure (MAP) was monitored with a catheter-transducer system through the left subclavian artery. The MAP responses to the rapid hemorrhage were averaged 8 times by a computer. G was calculated as G = delta API/delta APS-1, where delta API was an immediate MAP fall after the hemorrhage and delta APS was a steady-state error 1-2 min after the hemorrhage. The values of G in the conscious normal and WHHL rabbits were 7.35 +/- 0.24 and 1.91 +/- 0.29 (mean +/- SE, p < 0.01), respectively. To investigate effects of pentobarbital anesthesia on baroreflex system, the hemorrhage experiment was repeated several times under pentobarbital anesthesia (20 mg/kg, i.v.). The values of G in the anesthetized normal and WHHL rabbits were 6.69 +/- 0.23 and 1.68 +/- 0.34 (mean +/- SE, p < 0.01), respectively. G in the normal and WHHL rabbits did not show any significant change in the presence and absence of pentobarbital anesthesia (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420584 TI - Are there M cells in the cecal tonsil of chickens? AB - A unique morphological cell type, "microfold or membranous (M) cell-like cell", was detected electron-microscopically in the cecal tonsil epithelium of the chicken. M cell-like cells possessed a few short microvilli of irregular arrangement and a large number of lymphocytes and macrophages wedged into their basal surfaces. Triticum vulgaris was found to bind to M cell-like cells. With horseradish peroxidase (HRP) treatment, M cell-like cells showed an active HRP uptake just as did the neighbouring usual absorptive epithelial cells. No uptake of colloidal carbon particles from the intestinal lumen was recognized in any part of the intestinal epithelium. These results suggest that M cell-like cells of the chicken possess some M cell-characteristic morphological and histochemical features, but that their active uptake of foreign materials is not so developed as in mammalian M cells. PMID- 1420585 TI - [Acyl and plasmalogen analogs of platelet activating factor--new lipid cellular bioregulators]. AB - Recent data concerning two structural platelet-activating factor (PAF) analogs-1 O-acyl-2-acetyl-sn-glycero-3-phosphocholine (acyl-PAF) and 1-O-alk-1'-enyl-2 acetyl-sn-glycero-3-phosphocholine (vinyl-PAF) identified in some cells and tissues are reviewed. Isolation, identification, biosynthesis, and metabolism of acyl-PAF and vinyl-PAF are considered. The activity of acyl-PAF and vinyl-PAF towards platelets, leukocytes, isolated myocardium, and ileum as well as its in vivo activity are discussed. The influence of acyl-PAF and vinyl-PAF on PAF platelet interaction, Ca2+ mobilization, and platelet adenylate cyclase activity is considered. It is concluded that similar to PAF, acyl-PAF and vinyl-PAF should be regarded as a family of PAF lipid bioregulators. PMID- 1420586 TI - [Detection of apoprotein A-1 immunoreactivity in chromatin of rat hepatocytes]. AB - The binding of 125I-labeled lipoproteins to subcellular structures of rat hepatocytes was studied. The protein component of HDL, LDL, and VLDL was found in large and small membranes, nuclei, mitochondria, lysosomes, microsomes, and cell cytosol. The presence in liver nuclear chromatin of proteins immunochemically related to apoA-1 was demonstrated by solid phase immunoenzymatic analysis, dot immunoanalysis, and immunoelectroblotting. The apoprotein A-1 immunoreactivity was detected in transcriptionally inactive total chromatin, transcriptionally active chromatin, and nuclear matrix. The specific apoA-1 immunoreactivity of transcriptionally active chromatin and nuclear matrix was two times as low as that of total and transcriptionally inactive chromatin. Immunoelectroblotting revealed two proteins possessing an apoA-1 immunoreactivity (M(r) 28 and 14 kDa). The 28 kDa protein was found in transcriptionally active chromatin and nuclear matrix, while the 14 kDa one--only in transcriptionally inactive chromatin. the roles of apoproteins in lipid transport to nuclei and the maintenance of chromatin in a transcriptionally active state are discussed. PMID- 1420587 TI - [Two types of prolactin-binding sites on membranes of cow milk fat globules]. AB - Prolactin (PRL) binding to specific receptors of cow milk fat globular membranes (MFGM) has been studied. The data obtained point to the existence of two PRL binding sites on cow MFGM. The parameters of PRL binding to lactogenic receptors have been estimated for a two-binding-site model. PMID- 1420588 TI - [Substrate specificity of phosphoribosyl-aminoimidazole-succinocarboxamide synthetase (SAICAR-synthetase) from Saccharomyces cerevisiae yeast]. AB - The substrate specificity of phosphoribosyl-aminoimidazole-succinocarboxamide synthetase (SAICAR-synthetase, EC 6.3.2.6) of the yeast Saccharomyces cerevisiae towards a set of carboxyaminoimidazole ribotide (CAIR) analogs with modifications in the imidazole ring, ribose and phosphate moieties, as well as aspartic acid analogs has been studied. It was found, in particular, that: i) the presence of double charged phosphate group, 2'- and 3'-hydroxyl groups in the ribose fragment and of an amino group in the imidazole ring of the CAIR molecule is not the absolute requirement for the enzymatic reaction; ii) 3'-carboxy-1.2.4-triazole analog of CAIR is a competitive inhibitor of the enzyme; iii) 2'-deoxy-CAIR is a substrate for both yeast SAICAR-synthetase and its avian liver and human erythrocyte counterparts. A new method designed to determine the SAICAR synthetase activity with the help of bifunctional enzymes possessing, in addition to the SAICAR-synthetase activity, also a phosphoribosyl-aminoimidazole carboxylase activity, is proposed; this method is based on the use of 2'-deoxy CAIR. Some aspartic acid analogs (L-malic acid, beta-threo-oxy-, and beta-threo fluoro-aspartic acids and alanosine) are substrates for yeast SAICAR-synthetase. The possible involvement of malate as an alternative substrate for the SAICAR synthetase reaction in vivo is discussed. The results of a comparative analysis of already established primary structures of yeast, bacterial, human, and chicken SAICAR-synthetases are presented. PMID- 1420589 TI - [Effect of mevinolin and glycyrrhizinic acid on cholesterol and bile acid metabolism in cultured rabbit hepatocytes]. AB - A comparison of effects of two hypocholesterolemic drugs--mevinolin and glycyrrhizinic acid, on cholesterol and bile acid metabolism in cultured rabbit hepatocytes has been carried out. The following parameters have been determined: i) cholesterol synthesis from [2-14C]acetate; ii) bile acid production from newly synthesized and [4-14C]-labeled HDL2 cholesterol, and, iii) total cholesterol efflux into the incubation medium Mevinolin (0.5 microgram/ml) inhibited [2-14C] acetate incorporation into cholesterol by more than 90%. Conversely, glycyrrhizinic acid did not influence cholesterol synthesis even when used at high (100 micrograms/ml) concentrations but stimulated the conversion of endogenous (by 37%) and exogenous (by 18%) cholesterol into bile acids and increased, in addition, the proportion of bile acids in the total sterol pool released from hepatocytes into the incubation medium. At the same time, mevinolin used at 0.5 microgram/ml decreased the bile acid production by endogenous (by 27%) and exogenous (by 40%) cholesterol. The data obtained suggest that glycyrrhizinic acid exerts hypocholesterolemic action by stimulation of cholesterol conversion into bile acids without any effect on cholesterol synthesis. As for mevinolin, it has a cholesterol-suppressing effect via a mechanism of cholesterol synthesis inhibition only. PMID- 1420590 TI - [Comparative study of the features of protein composition of human aorta tunica media]. AB - A preliminary two-dimensional map of human aorta tunica media proteins comprising 280 polypeptide fractions has been constructed. Individual protein fractions were characterized in terms of molecular masses and relative electrophoretic mobility; the resulting values were stored in the "protein" data base. Using co electrophoresis, the positions of certain tunica media proteins (light chains, myosin, tropomyosin, actin, albumin) was determined. The two-dimensional map was used to compare tunica media proteins with their human cardiac muscle counterparts. PMID- 1420591 TI - [Activation of Na/H exchange by thrombin in peritoneal mast cells]. AB - Using the fluorescent probe, BCECF, the changes in intracellular pH (pHi) in rat peritoneal mast cells were studied. alpha-Thrombin (0.1 nM) induced biphasic changes in pHi which consisted in a temporary decrease in pH with its subsequent steady increase due to the Na/H exchange activation which was inhibited by EIPA and controlled by extracellular Na+. The biphasic changes in pHi induced by DIP alpha-thrombin (0.1 pM-1 nM), a catalytically inactive form with an intact recognition site, were similar to those of alpha-thrombin, whereas beta/gamma thrombin (10-1000 pM), a catalytically active form characterized by structural disturbances in the recognition site, was able to induce only the initial phase of acidification. The thrombin recognition site modulators, alpha 1-thymosin and heparin, blocked the ability of the enzyme to induce the alkalinization of pHi. Nigericin stimulated the Na/H-exchange in mast cells. The rate of the Na/H exchange activation determined with nigericin, decreased with an increase in the alpha-thrombin dose from 0.1 pM up to 10 nM. Activation of protein kinase C (PKC) in mast cells by PMA used at 1 nM and 10 nM led to the alkalinization of the cytoplasm as a result of the Na/H-exchange activation blocked by EIPA. The PKC inhibitor, H-7, suppressed the pHi increase induced by both PMA and alpha thrombin. The alpha-thrombin-induced acidification of the cytoplasm was completely blocked by SITS in Ca(2+)-free media, whereas in media with Ca2+ SITS inhibited the pHi decline. Acidification of the cytoplasm by thrombin seems to be due to both Ca2+ influx and activation of Cl- fluxes. It is concluded that the observed activation of the Na/H-exchange by thrombin is induced by a cascade of intracellular reactions involving PKC. PMID- 1420592 TI - [Hydrolysis of prolactin by a serine proteinase from mammary gland secretory cell mitochondria]. AB - Mitochondrial proteinase isolated from secretory cells of the mammary gland of lactating rats able to hydrolyze 125I-labeled and native prolactin (PRL) has been studied. The enzyme represents a serine proteinase and is localized in the inner mitochondrial membrane. The molecular mass of the enzyme is 17-18 kDa, pH optimum is at 8.0-9.0. Partial purification of the enzyme has been carried out. The Km constant for 125I-PRL is equal to 10(-6) M, that for 2% hemoglobin is 1.2 x 10( 4) M. Analysis of products of rat and ovine PRL hydrolysis by proteinase using high performance liquid chromatography and PAAG electrophoresis revealed the formation of large-size fragments of the hormone. A possible role of proteinase in the mechanism of PRL action on mammary gland tissues is discussed. PMID- 1420593 TI - Morphometric analysis of sciatic nerve and its main branches in the rabbit. AB - In the rabbit the myelinated fibres with the largest diameter originating from the sciatic nerve distribute mainly into the peroneal nerve, even though there is no difference in the density of myelinated fibres of the representative unit between the sciatic nerve and its branches. The distribution of the myelinated fibre diameters is unimodal in the sciatic nerve, but bimodal both in the peroneal and tibial nerves. The quotient axon diameter/fiber diameter (g ratio) shows a different trend between the sciatic nerve and the branches originating from it. Except for the peroneal nerve, the increase of the axon calibre corresponds to the reduction of the relative myelin sheath thickness and therefore to the reduction of internodal distance. The results show that the sciatic nerve and its terminal branches in the rabbit have morphometrical characteristics that are peculiar and differ from those of the other rodents. PMID- 1420594 TI - The oxytocin positive elements in the hypothalamic magnocellular nuclei of rats treated with histamine. AB - The oxytocin positive elements of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, were instigated in 160 male rats through immunohistochemical, morphometric and statistical methods. The rats subdivided into five groups: 20 control rats; 20 rats treated with physiological saline intraperitoneal via (ip); 20 rats treated with physiological saline intracerebroventricular via (icv); 20 histamine (HA) treated rats, ip; and 20 HA treated rats, icv. Some labeled nerve cells appear, mainly, in the lateral part of the SON and the PVN of the control animals. These neurons have central nucleus and oxytocin positive cytoplasmic granulations. After the treatment with physiological saline, ip or icv, no alterations were observed. In HA treated rats, icv, numerous neurons and pathways were observed strongly labeled. Large droplets appear in the SON and in the PVN of these animals. In HA treated rats, ip, the oxytocin positive material is similar to that observed in the control rats. The morphometric and statistical studies confirm these findings. The results are discussed in this paper. PMID- 1420595 TI - Influence of chick or quail embryonic testes on the reproductive system of the quail embryo. AB - The reproductive system of female quail embryo undergoes masculinization under the influence of chick and quail embryonic testis grafted into an extraembryonic coelom. Mullerian ducts undergo regression. The left gonad transforms into an ovotestis and the right gonad either does not develop or transforms into a small testis. Testicular chick or quail graft does not affect the development of the cortical ovarian-like region in the left testis of male hosts. In some quail testicular grafts developing in female quail hosts cortical region is retained longer than normally. PMID- 1420596 TI - Characterization of the nuclear receptors of triiodothyronine (T3) by immunocytochemistry under electron microscopy. AB - By immunocytochemical methods, using colloidal gold particles coupled to antibodies, it is possible to label the occupied nuclear T3 receptors and observe them by electron microscopy. We carried out some experiments to validate these methods by testing the absence of non-specific binding of the antibodies to subcellular structures different from the T3 receptors. So, we have verified that the number of occupied T3 receptors in tissues from normal rats is lower in kidney cells than in heart and liver ones, a finding which is an agreement with data reported by others. The occupation of the receptors increases after T3 administration and decreases by triiodothyroacetic acid (Triac) administration to the rats, due to the displacement of T3 from the receptors with the latter. Our results are similar to those of the other authors using radioactive tracers. Non specific binding was not detected. The occupied T3 receptors labelled with colloidal gold particles are located most commonly in the hetero/euchromatin interface. From our results we conclude that the colloidal gold particles observed by electron microscopy specifically label occupied T3 receptors, and the determination of the thyroid status at cellular level can be achieved using electron microscopy after labelling the receptors by immunocytochemistry with colloidal gold particles coupled to antibodies. PMID- 1420597 TI - Selective species specificity of tumor necrosis factor for toxicity in the mouse. AB - The selective cytotoxic activity of tumor necrosis factor (TNF) on many transformed human or murine cell lines is (almost) not species-specific. There are, however, a limited number of biological assay systems such as gene induction in murine thymoma cells and the murine thymocyte proliferation assay, in which recombinant murine (rm) TNF, but not recombinant human (rh) TNF is active. We have now investigated the possible species specificity of the lethality-inducing properties of TNF in the mouse. When administered alone, only rmTNF, but not rhTNF caused lethality. This difference was not due to a different endotoxin contamination or to a different pharmacokinetic behavior. When a sensitizing agent, galactosamine, was added, the species specificity was abolished. We have shown previously that similar conclusions could be drawn for at least some of the antitumor mechanisms of TNF. We conclude that to mimic the two major phenomena caused by endotoxin administration, viz. lethality and antitumor effect, two distinct signals are needed. In mice, rmTNF can provide both, while rhTNF needs another agent (a sensitizer) to cause systemic toxicity. The results are discussed with respect to recent findings showing that, in the mouse, rhTNF can only bind to the TNF-R55 receptor type, while rmTNF can bind both to the TNF-R55 and TNF-R75 receptor types. PMID- 1420598 TI - Glycosylation of the interleukin-1 receptor type I is required for optimal binding of interleukin-1. AB - The two types of cell surface receptors for interleukin-1 (IL-1) are glycoproteins that contain N-glycosidic chains on their extracellular portions. To determine the role of glycosylation of the IL-1 receptor type I (IL-1RtI) in the binding and function of IL-1, we used four plant lectins and glycosidase treatment on two different T-cell lines (EL4-6.1 and D10S) and expressing high number of binding sites for IL-1. The lectins wheat germ agglutinin, phytohemagglutinin, and concanavalin A inhibited in a dose-response manner the IL 1-induced proliferation of D10S cells. Binding of IL-1 was blocked and radioactive IL-1 was displaced from these cells by these lectins. Specific sugars (GlcNAc, NeuAc, Gal-GlcNAc-Man, Man, or alpha-MeMan) did not themselves affect IL 1 binding but reversed the blocking effects of the lectins. The two cell lines differed in their responses to the lectin-mediated inhibition of IL-1 binding. Digestion by N-glycosidase significantly decreased the capacity of cells to bind IL-1, and reduced by approximately 20,000 D the M(r) of the IL-1RtI. Neuraminidase and O-glycanase treatment did not alter the binding of IL-1 to D10S or EL4-6.1 cells. This study demonstrates that glycosylation of the extracellular domain of the IL-1RtI is due to N-linked carbohydrates, that the degree of glycosylation can vary in cells of different lineage, and that this N-linked glycosylation appears to be essential for optimal binding and activity of IL-1 to its type I receptor. PMID- 1420599 TI - Tumor recognition and lytic competence of IL-2-activated lymphocytes: regulation of both antibody-independent and -dependent cellular cytotoxicity via P75 IL-2 receptor. AB - Fc receptor-positive lymphocytes (FcR+) contain lymphokine-activated killer cell (LAK) precursors that in response to IL-2 develop potent antitumor cytotoxicity. These FcR+ cells are also capable of antibody-dependent cytotoxicity (ADCC), which can be detected using fresh human peripheral blood lymphocytes (PBL) directed to murine targets, however, PBL-mediated ADCC to human tumors usually is very low, requiring a stimulation of the PBL, which also can be accomplished with IL-2. Using human melanoma tumor target cells, with and without the 14G2a monoclonal antibody, we examined in parallel the role of p75 IL-2 receptor for regulation of the induction of both LAK and ADCC forms of antitumor cytotoxicity. Enrichment of FcR+ cells from fresh peripheral blood by elutriation and flow cytometry, followed by varying periods of IL-2 culture, revealed a differential kinetics of activation. ADCC was detectable after PBL exposure to IL-2 for as short as the 4 h cytotoxicity assay, while LAK activation required more than 24 h of exposure. Elimination of the FcR+ cells by magnetic bead depletion from large granular lymphocyte populations (LGL) resulted in a loss of both LAK and ADCC. Addition of antibody known to block the binding of IL-2 to the p75 molecule of the IL-2 receptor complex (Mik-beta 1) to activation cultures at zero time resulted in abrogation of both cytotoxicities. These results suggest that differentiation and maturation of the ADCC effectors occurs in response to IL-2 via the p75 molecule, as also does LAK activation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420601 TI - Comparative tissue distribution of 125I- and U-14C-labeled recombinant human interleukin-2 in the rat. AB - The distribution of recombinant human interleukin-2 (rhIL-2) after intravenous administration of 125I- or U-14C-labeled rhIL-2 is reported in the major organs of the rat. Five minutes after the administration of U-14C-labeled rhIL-2, the radioactivity had been rapidly cleared from the plasma, while 38% of the dose was found in the kidneys, confirming that the major site of clearance for rhIL-2 is the kidney. After 1 h, a large fraction of the radioactivity had disappeared from the kidney and was found in the carcass. When the same experiments were carried out with 125I-labeled rhIL-2, comparable distribution results were obtained: Preferential accumulation of 125I radioactivity (37.4%) was found in the kidney at 5 min after iv administration of 125I-labeled rhIL-2. One hour after dosing 125I label was predominantly present in the carcass (46%) and skin (15%). Similar percentages of the dose of 125I or 14C radioactivity were present in other organs or tissues. The present study indicates a similar distribution of the radiolabel in selected tissue and organs regardless of whether 14C or 125I was employed. PMID- 1420600 TI - The immunomodulatory role of IFN-alpha or maltose-stabilized IFN-alpha on T-cell activation. AB - The effects of human interferon-alpha (IFN-alpha) or maltose-stabilized IFN-alpha (MS-IFN-alpha) on IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells, a human leukemic T cell line, were studied. MS-IFN-alpha is an IFN-alpha containing powder in which maltose was used as an excipient, and has been shown to have a positive effect on human immunodeficiency virus (HIV)-infected patients. In this study, MS-IFN-alpha powder was dissolved in a culture medium and used for the experiments. IL-2 production by PHA- or anti-CD3 mAb-stimulated MOLT 16 cells was augmented by coculturing with IFN-alpha or MS-IFN-alpha. The augmentation of IL-2 production by IFN-alpha or MS-IFN-alpha was completely abrogated by rabbit anti-IFN-alpha antibody. We have previously shown that IL-2 production by PHA-stimulated MOLT 16 cells is augmented by coculturing with IL-1. Furthermore, IL-2 production by PHA-stimulated MOLT 16 cells was also augmented by human TNF-alpha in a dose-dependent manner. The TNF-alpha-induced augmentation was completely abrogated by rabbit anti-TNF-alpha antibody. Interestingly, both IFN-alpha and MS-IFN-alpha synergized with rIL-1 alpha or TNF-alpha resulting in IL-2 production being augmented far more effectively than either cytokine alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420602 TI - Modulation of the posthemorrhage bacterial polysaccharide antigen-specific antibody response by interleukins 2 and 4. AB - Abnormalities in immune response play a major role in the increased susceptibility to infection after hemorrhage and trauma. Several studies have shown decreased release in vitro of interleukin-2 (IL-2) following blood loss. To better define in vivo the interactions between T and B cells, as well as the effects of treatment with the T cell-derived cytokines IL-2 and IL-4, mice were injected with concanavalin A at predetermined times posthemorrhage, and the percentages and numbers of splenic plasma cells producing antibody to the bacterial polysaccharide antigen levan (from Aerobacter levanicum) were determined. Decreased numbers and percentages of levan specific splenic plasma cells were found in animals treated with concanavalin A both immediately and 2 to 4 days after hemorrhage. Treatment in vivo with recombinant IL-2, but not IL-4 or anti-IL-2 receptor antibodies, following blood loss was able to increase the numbers of levan specific plasma cells to levels as high or higher than those found in normal, unhemorrhaged animals, but was unable to affect the decreased percentage of levan specific splenic plasma cells. These results suggest that the use in vivo of IL-2 may restore bacterial antigen specific antibody responses to normal levels after blood loss. PMID- 1420604 TI - Business forms: interviewing potential plaintiff-clients. PMID- 1420605 TI - Communicate what you intend for effective image building. PMID- 1420603 TI - Accounting systems for small businesses. PMID- 1420606 TI - Toxic torts: superfund--key factor in hazardous waste issue. PMID- 1420607 TI - Hedonic damages. PMID- 1420608 TI - Ontogeny of intestinal lipid and lipoprotein synthesis. AB - Despite increasing evidence that the fetal intestine produces apoproteins, there is limited knowledge about its ability to absorb fat. The present study focused on the intracellular processing of lipid formation and transport by lipoproteins in the developing fetus. Explants of fetal jejunum (14-20 weeks) were maintained in serum-free organ culture for 42 h with [14C]-oleate. Esterified lipids extracted from the tissue showed an abundance of phospholipids (PL; 54-77%), while those harvested from the medium displayed a predominance for triglycerides (TG; 68-73%). Only a minor percentage of radioactivity was recovered in cholesterol ester (CE) from the tissue (1.8-2.5%) or medium (1.3-2.5%). Separation of PL by thin-layer chromatography revealed a prevalence of phosphatidylcholine followed by phosphatidylethanolamine. Over the fetal period studied a trend towards increase was noted in TG, CE and most of the PL classes but not phosphatidylcholine. In parallel, we observed a progressive increase in these lipoprotein fractions produced by the fetal intestine during development, i.e., chylomicrons, very low-density lipoproteins and high-density lipoproteins. Our data stress not only the ability of the fetal intestine to absorb fat, but also the ontogenetic changes of lipid and lipoprotein synthesis. PMID- 1420609 TI - Measurement of total bodywater volume with deuterated water in newborn infants. AB - D2O and H2(18)O are often used as tracers for the determination of total body water (TBW). For newborn infants, the commonly used noninvasive method has not been validated. In this study TBW was calculated from D2O concentrations in blood and compared with TBW calculated from D2O concentrations in urine. TBW calculated from all urine portions voided at least 6 h after D2O administration on average was 1.0% lower. TBW calculated from only three urine portions voided 6, 12, and 24 h after D2O administration was 0.6% (mean) lower compared to TBW calculated from D2O concentrations in blood. This study indicates that the noninvasive method to measure TBW can be considered a reliable method when used in newborn infants. PMID- 1420610 TI - GTP-dependent protein(Gs) activity in preterm infants. AB - In a previous study, we showed a renal resistance to PTH in preterm infants during their 1st week of life. We proposed it could explain early neonatal hypocalcemia. Such renal resistance is well known in type 1 pseudohypoparathyroid patients and is explained by a defect of stimulatory GTP-dependent protein (Gs). To determine if functional immaturity in the Gs protein could be involved in PTH resistance, we studied 27 newborn babies: 7 full-term and 20 preterm babies. Biological activity of the Gs unit was determined on days 1, 3 and 10 after delivery by bioassay. No correlation was found between the Gs unit activity and either gestation or birth weight at these dates. Eight infants had hypocalcemia and their Gs unit activity did not differ from those with normocalcemia. Furthermore, we showed that the Gs unit is active from 29 weeks of gestation. We conclude that the Gs protein appears not to be involved in the pathophysiology of early renal resistance to PTH and therefore in early neonatal hypocalcemia. PMID- 1420611 TI - Ovine maternal and fetal glomerular atrial natriuretic factor receptors: response to dehydration. AB - In pregnancy, dehydration produces marked effects on maternal and fetal body water homeostasis including an increase in fetal urinary sodium concentration and excretion. To examine the role of fetal plasma atrial natriuretic factor (ANF) and glomerular ANF receptors in dehydration-induced natriuresis, we compared plasma ANF levels and glomerular ANF binding characteristics in dehydrated and control maternal and fetal sheep. Mean (+/- SEM) maternal and fetal plasma ANF levels in control animals (n = 9) at 132-136 days gestation were 37 +/- 3 pg/ml and 138 +/- 20 pg/ml, respectively. Although mean ANF receptor maximum binding capacities (Bmax) were significantly higher in maternal than in fetal glomeruli (83 +/- 11 vs 34 +/- 12 fmol/mg protein, respectively), the dissociation constants (Kd) for ANF binding were not different (2.7 +/- 0.6 and 3.7 +/- 1.7 x 10(-10) M, respectively). In an additional 9 animals studied after 63 +/- 4 h of water deprivation, maternal plasma ANF levels were significantly lower than in the control group (14 +/- 4 vs. 37 +/- 3 pg/ml), maternal glomerular ANF receptor Bmax values were significantly higher (732 +/- 203 vs. 83 +/- 11 fmol/mg protein), and Kd values were six-fold higher (17.0 +/- 7.1 vs. 2.7 +/- 0.6 x 10( 10) M), although this difference was only marginally significant (p = 0.06). In contrast to the adult, there was a small, nonsignificant decrease in plasma ANF levels and no difference in Bmax or Kd values between the dehydrated and euhydrated fetal animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420612 TI - Effect of hypoxia on renal prostaglandin E2 production in human and rat neonates. AB - Effect of hypoxia on renal prostaglandin E2 (PGE2) production was shown in asphyxic newborn infants and experimental hypoxic rats. In asphyxic infants, at postnatal day 1, the urinary excretion of PGE2 in severe asphyxia (1.00 +/- 0.19 pg/kg/min, n = 10) was lower than that of the mild asphyxia (2.15 +/- 0.18 pg/kg/min, n = 10) or normal newborn infants (2.65 +/- 0.25 pg/kg/min, n = 8) (p less than 0.01). The urinary excretion of PGE2 was inversely correlated with the urinary N-acetyl-beta-D-glucosaminidase (r = -0.84, p less than 0.01). The urine volume in mild asphyxia (0.04 +/- 0.005 ml/kg/min) was higher in comparison to normal newborn infants (0.026 +/- 0.002 ml/kg/min) (p less than 0.01), but had no correlation with the urinary excretion of PGE2. In experimental hypoxic rats, the renal PGE2 concentration increased from 0.19 +/- 0.02 ng/mg protein to the maximum level of 0.59 +/- 0.03 ng/mg protein at 10 min of hypoxia. The renal PGE2 concentration then decreased to the minimum level (0.105 +/- 0.02 ng/mg protein) at 24 h after 20 min hypoxia. The renal ATP rapidly decreased during 20 min hypoxia, and gradually increased to 55.1 +/- 6.2 nmol/mg protein at 24 h after 20 min hypoxia, which recovered only about 60% of the control level. It seems likely that renal PGE2 does not play a major role in diuresis in mild birth asphyxia and that severe birth asphyxia suppresses the renal PGE2 production in early neonatal period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420613 TI - Effect of dexamethasone on antioxidant enzymes in fetal rat lungs and kidneys. AB - To determine if an enhancement in the fetal antioxidant enzyme (AOE) system by maternal dexamethasone (DEX) is specific to organ and dose, the lung and kidney of pups, whose mother received DEX (0.2 or 2 mg/kg) twice, were obtained on days 19 and 20 of gestation. Low-dose DEX increased the four AOE in the day-19 lung, but not in day-20 lung. High-dose DEX decreased the copper-zinc superoxide dismutase (SOD) and glutathione peroxidase in the lungs. Thus, the DEX-induced maturation of lung AOE is dependent on dose and timing. DEX enhanced the four AOE in the day-19 kidney at both doses. In the day-20 kidney, DEX enhanced the manganese SOD at the low dose and also catalase at the high dose, suggesting that DEX accelerates the maturation of kidney AOE as well. PMID- 1420614 TI - Intestinal development and fatty acid binding protein activity of newborn pigs fed colostrum or milk. AB - Newborn pigs (n = 20) were gavage-fed sow's colostrum, defatted colostrum, milk, defatted milk or a 5% lactose solution over 24 h in order to evaluate effects on growth and functional differentiation of small intestine. Colostrum-fed pigs had greater (p less than 0.01) mucosal mass in the proximal half of the small intestine than did the milk- or lactose-fed groups. Total fatty acid binding protein (FABP) activity and FABP activity per mg DNA in proximal intestines of colostrum-fed pigs exceeded that for the lactose group. FABP activities (per g mucosa or mg soluble protein) were greater (p less than 0.01) in the proximal segments of small intestines of pigs fed whole versus the corresponding defatted secretion. These results indicate that the feeding of colostrum specifically augments perinatal intestinal growth and differentiation as manifested by increased cellular hypertrophy and FABP activity. Milk lipid and unidentified factor(s) enriched in colostrum are inducers of intestinal FABP activity. PMID- 1420615 TI - Hemodynamic effects of continuous negative extrathoracic pressure and continuous positive airway pressure in piglets with normal lungs. AB - The hemodynamic effects produced by continuous positive airway pressure (CPAP) and continuous negative extrathoracic pressure (CNEP) of 4 and 8 cm H2O were compared in 8 normal, spontaneously breathing piglets. Arterial blood gases and hemodynamic measurements were obtained before and during CPAP and CNEP of 4 and 8 cm H2O. CPAP 8 cm H2O and CNEP 8 cm H2O produced significant increases (p less than 0.01) in PaO2 from baselines 76 +/- 3 to 85 +/- 3 and 77 +/- 4 to 85 +/- 3 mm Hg, respectively. No significant changes occurred in PaCO2 or cardiac index, except during CPAP 8 cm H2O [38 +/- 1 to 44 +/- 2 mm Hg (p less than 0.05) and 376 +/- 30 to 330 +/- 30 ml/kg/min (p less than 0.05), respectively]. During CPAP of 4 cm H2O, significant increases occurred in mean right atrial pressure (Pra) (2.1 +/- 0.3 to 3.3 +/- 0.4 mm Hg; p less than 0.01), left ventricular end diastolic pressure (LVEDP) (2.8 +/- 0.4 to 3.7 +/- 0.3 mm Hg; p less than 0.01), and mean pulmonary artery pressure (Ppa) (12.9 +/- 0.8 to 15.1 +/- 0.8 mm Hg; p less than 0.01). CPAP of 8 cm H2O produced marked increases in Pra (2.1 +/- 0.2 to 4.9 +/- 0.7 mm Hg; p less than 0.01), LVEDP (2.7 +/- 0.5 to 4.5 +/- 0.4 mm Hg; p less than 0.01) and Ppa (12.8 +/- 0.8 to 17.7 +/- 0.6 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420616 TI - Urinary and plasma epidermal growth factor levels are decreased in neonates with intrauterine growth retardation and in their mothers. AB - Epidermal growth factor (EGF) concentrations in urine and plasma samples collected from pregnant women and neonates were measured by RIA. The EGF concentration of the first voided urine was higher in appropriate-for-date (AFD) neonates (33.9 +/- 23.0 ng/mg creatinine) than in those with intrauterine growth retardation (IUGR; 23.5 +/- 7.7 ng/mg creatinine, p less than 0.05) and heavy-for date (19.8 +/- 5.2 ng/mg creatinine, p less than 0.05) neonates. The urinary EGF concentration of pregnant women showed no marked changes throughout pregnancy. Urinary EGF concentrations of women with AFD fetuses (45.9 +/- 31.2 ng/mg creatinine) did not differ significantly from those of women with diabetes (39.9 +/- 26.8 ng/mg creatinine) or women with multiple fetuses (44.6 +/- 30.6 ng/mg creatinine). However, women with IUGR fetuses showed lower urinary EGF concentrations (13.8 +/- 7.4 ng/mg creatinine, p less than 0.05) than women with AFD fetuses. Maternal and fetal platelet-poor plasma EGF concentrations at delivery were lower in the IUGR group (mother: 2.62 +/- 0.38 ng/ml, fetus: 2.16 +/- 0.07 ng/ml, respectively, p less than 0.05 and p less than 0.005) than in the AFD group (mother: 3.34 +/- 0.64 ng/ml, fetus: 3.24 +/- 0.93 ng/ml). In the IUGR group, the EGF concentration in fetal blood was always lower than that in maternal blood (p less than 0.05), although the AFD groups showed no such difference. These data suggest that EGF levels are closely related to fetal growth. PMID- 1420617 TI - Developmental changes of glutamate dehydrogenase activity in rat liver mitochondria and its enhancement by branched-chain amino acids. AB - The developmental changes of glutamate dehydrogenase activity in the fetal and neonatal rat liver were investigated, as well as the effects of branched-chain amino acids on this enzyme. Hepatic glutamate dehydrogenase activity showed a marked increase at the end of the fetal period and peaked on the 5th day of neonate at approximately 3 times higher than the adult level. Glutamate dehydrogenase was activated by leucine, isoleucine, and valine in this order when they were added to isolated intact liver mitochondria in vitro. The enhancement of enzyme activity was more marked in fetal rats than in adults. In contrast, when branched-chain amino acids were added after disrupting the mitochondrial membrane by sonication, only leucine slightly activated glutamate dehydrogenase, while isoleucine and valine slightly inhibited its activity. Our findings suggest that glutamate may be actively synthesized in the developing rat liver mitochondria and then transaminated to other nonessential amino acids for protein synthesis, and that increased intramitochondrial branched-chain amino acid concentrations may enhance glutamate dehydrogenase activity. This anabolic metabolism will contribute to the fetal growth and development. PMID- 1420618 TI - Urodilatin and atrial natriuretic peptide are present in the urine of healthy neonates and young infants. AB - Urine sampling has been proposed as noninvasive monitoring of plasma atrial natriuretic peptide (ANP) in neonates, assuming urine contains only filtered plasma ANP. Recently, urodilatin, another natriuretic peptide, which is cross reactive to ANP in the ANP radioimmunoassay (ANP-RIA), has been isolated from the urine of adults. We studied the urine of healthy term neonates and young infants for the presence of urodilatin. In all urine samples, we found three peaks of ANP RIA-reactive material: the first one in the position of urodilatin, the second one coeluting with synthetic ANP and a third late eluting peak, possibly containing degradation products. The physiological significance of these findings remains to be investigated. PMID- 1420619 TI - Some animal models for the study of perinatal asphyxia. AB - Much of our current understanding concerning the pathophysiology of perinatal brain disorders has evolved from animal studies over the past three decades. Fetal and neonatal nonhuman primate, pregnant sheep, lamb, puppy, piglet and immature rodents, all have been important animal models for perinatal brain research. Although no model can be considered 'perfect' in reflecting the variety and complexity of human brain pathology, the investigator must assess the merits and limitations of each model within the framework of the research questions being asked. A variety of experimental designs have been used over the years and variations of particular interest are the animal age, the method of producing brain insult and the procedures used for evaluating outcomes. Most models relating to the study of intracranial hemorrhage, cerebral blood flow and cerebral energy metabolism have generally been acute preparations. Some important long-term survival models have also been developed in recent years for the study of hypoxic-ischemic encephalopathy. The latter include the nonhuman primate, piglet, sheep and immature rat models. In this article, I have reviewed some important animal models used in perinatal brain research with emphasis on those relating to perinatal asphyxia and intracranial hemorrhage. PMID- 1420620 TI - Effect of glucose on perinatal hypoxic-ischemic brain damage. AB - Investigations suggest that hyperglycemia superimposed on hypoxia-ischemia or cerebral ischemia accentuates brain damage in adult experimental animals and humans. Such does not appear to be the case in immature animals. The present review discusses fundamental differences in immature and adult brain metabolism which account for the age-specific paradox. Based on currently available data, it is recommended that glucose supplementation not be curtailed during labor and delivery of asphyxiated human infants; on the contrary, glucose therapy might substantially reduce hypoxic-ischemic brain damage. PMID- 1420621 TI - Brain injury in the premature infant--current concepts of pathogenesis and prevention. AB - Brain injury in the premature infant and, particularly, the prevention of that injury is an enormous problem. With modern neonatal intensive care, approximately 85% of very low birth weight infants survive, and of these survivals, approximately 5-15% exhibit major spastic motor deficit, grouped under the rubric, 'cerebral palsy', and an additional 25-50% exhibit less prominent developmental disabilities, particularly school failure. PMID- 1420622 TI - Ischaemia of the preterm brain. AB - Much has been learned about the diagnosis and prognosis of periventricalar leucomalacia during the past 10 years. The understanding of its causation, however, has not advanced much. Still, the candidate for the principal role is focal ischaemia in the particularly vulnerable regions of the brain. It has been difficult to provide direct supportive evidence for this hypothesis. It has not been possible to define a threshold for (global) cerebral blood flow (CBF) under which brain damage or electrical dysfunction occurs. Three hypothetical explanations for the lack of clear relation between global CBF and electrical brain activity of the preterm infant must be examined more closely: (1) the very low levels of CBF are adequate, (2) global CBF does not reflect the perfusion of the white matter, or (3) acute white-matter ischaemia does not result in cerebro electrical dysfunction. In view of the practical importance, more research is indicated. PMID- 1420623 TI - Perinatal pharmacology and cerebral blood flow. AB - Many of the drugs used in neonatal intensive care units might impede cerebral blood flow, thereby increasing the risk of intraventricular hemorrhage and periventricular leukomalacia. Our studies focussed on sick preterm neonates who were treated with the following drugs: caffeine (20 mg/kg i.v., as caffeine citrate); phenobarbital (loading dose: 20 mg/kg); indomethacin (0.2 mg/kg/dose, every 12 h three doses), and synthetic surfactant (Exosurf; 50 mg/kg = 5 ml/kg intratracheally). All of the drugs studied, except indomethacin, had no adverse effect on cerebral hemodynamics. PMID- 1420625 TI - Cerebral function in the growth-retarded fetus and neonate. AB - Intrauterine growth retardation is associated with increased risks for permanent neurological disabilities. A series of studies was undertaken to elucidate whether fetal growth retardation causes a primary perturbation of brain function and development and whether an increased vulnerability for periods of oxygen lack exists. In two groups of neonates who were small for gestational age (SGA) evoked potentials were investigated. A high frequency of abnormal recordings were obtained in SGA babies. SGA babies had significantly longer latency periods for the primary evoked potentials than appropriately grown controls. In guinea pigs and rats growth retardation was induced by reducing the placental blood flow during late gestation. Growth retarded guinea pups demonstrated a considerable reduction of the ability to retain normal somatosensory evoked response during hypoxia compared to appropriately grown littermates. Growth retarded rat fetuses exhibited marked changes of the monoamine metabolism in the brain inasmuch as basal levels of serotonin and its main metabolite were low while an inappropriate acceleration of the serotonin synthesis rate took place during hypoxia. The tissue concentrations of aspartate were also significantly lower in growth retarded fetuses than normally grown littermates. Finally, lipid peroxidation was assessed. During adequate oxygenation no difference was observed when lipid peroxidation was assessed. During adequate oxygenation no difference was observed when lipid peroxidation in brain tissue of growth retarded and appropriately grown fetuses was compared but during mild-moderate hypoxia lipid peroxidation was significantly more intense in the growth retarded group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420624 TI - Intrauterine blood flow and postnatal neurological development in growth-retarded fetuses. AB - Intrauterine growth retardation (IUGR) is associated with abnormal neuro developmental outcome. Aortic blood flow velocity waveforms have been shown to predict fetal distress in IUGR. Fetal aortic blood flow velocity waveforms were correlated to neuro-developmental performance at 7 years of age. Results suggest that abnormal fetal aortic blood flow velocity waveforms are associated with neuro-developmental impairment. PMID- 1420626 TI - Doppler ultrasound and the neonatal cerebral circulation: methodology and pitfalls. AB - Doppler ultrasound is a popular technique for investigating the haemodynamics of the neonatal cerebral circulation. Different types of instrumentation are available of which a duplex scanner is a suitable choice for spot measurements, whilst a simple continuous wave directional Doppler may be better for long-term monitoring purposes. Doppler signals may be obtained from many arterial and venous sites within the neonatal brain, but most measurements are made from the anterior or middle cerebral arteries. It is usual to process the Doppler signal to obtain an envelope waveform which may represent either mean velocity or maximum velocity, although the latter has some distinct advantages. The zero crossing detector used for early studies is unsuitable for use with Doppler signals. Changes in the shape of the velocity waveform may be quantified using different methods, of which the so-called resistance index is the most popular. It is also possible to make absolute velocity measurements, although these cannot be converted to flow because it is not possible to measure the diameter of neonatal cerebral vessels. There is considerable controversy as to whether the diameter of the vessels at the sites of ultrasound insonation can be affected by factors such as blood pressure and arterial gases, but it is unlikely that any such changes could invalidate the basic findings of Doppler studies. With care and attention to detail, Doppler ultrasound provides a valuable window on the neonatal cerebral circulation. PMID- 1420627 TI - Hemodynamic foundation of umbilical arterial Doppler waveform analysis. AB - This paper reviews various in vitro and in vivo studies which have been conducted to investigate the influence of central and peripheral circulatory factors on the Doppler indices. These studies indicate that the Doppler indices are affected by both central and peripheral hemodynamics. Of the central factors, the heart rate influences the indices predominantly through the variations during the diastolic phase of the cardiac cycle. This was confirmatory of the clinical findings. Of the other central factors, cardiac contractility may not affect the rising slope of the Doppler waveform. Regarding the peripheral hemodynamics, both in vitro and in vivo studies confirm that the indices reflect the changes in the peripheral resistance; however, opposition to flow in a pulsatile flow can be adequately described only by impedance. Initial in vivo and in vitro studies demonstrate that the indices correlate well with the impedance parameters. However, this is true only when the central circulation remains stable. PMID- 1420628 TI - Near infrared spectroscopy. Investigation and assessment of perinatal brain injury. AB - Near-infrared spectroscopy is a new technique for noninvasive monitoring of tissue oxygenation and haemodynamics. Quantitative measurements can be made of oxyhaemoglobin, deoxyhaemoglobin, oxidized cytochrome and various haemodynamic indices. This technique is likely to prove increasingly valuable for: cot-side monitoring brain oxygenation and haemodynamics in babies; investigating the mechanisms of damage to the brain; according the results of treatment; and assigning long-term prognosis. PMID- 1420629 TI - The dexamethasone suppression test in children and adolescents: a review and a controlled study. AB - Dexamethasone Suppression Test (DST) studies conducted in children and adolescents are reviewed, together with factors hypothesized to explain discrepancies in rates of DST nonsuppression across studies. These factors are then examined in a controlled study of 27 adolescents with major depressive disorder (MDD) and 34 normal controls (NC). Subjects were given 1 mg of dexamethasone at 11:00 PM, and the following day serum samples for cortisol were collected each hr from 8 AM to 11 PM through an indwelling catheter. There were no significant differences found between the MDD and NC subjects on any postdexamethasone cortisol measure. Further, cortisol suppressors and nonsuppressors were not distinguished by any of the hypothesized factors identified from the review, including inpatient status, presence of suicidality, endogenous features, psychotic symptoms, or prior history of MDD. Questions about the appropriateness of the 1 mg dose of dexamethasone (currently the standard dose used with adolescents) are raised, together with a discussion of the effects of stress on DST findings. PMID- 1420630 TI - Changes in middle cerebral artery velocity after marijuana. AB - Velocity of blood flow in the middle cerebral artery was measured with transcranial Doppler flowmeter before, during, and 1 hr after smoking a marijuana cigarette and a placebo cigarette during two separate visits to the laboratory. Ten healthy, right-handed male volunteers with a history of marijuana smoking took part in the study. The participants were drug-free for a minimum of 3 mo before the project. During the experiment, blood pressure, pulse rate, and end tidal levels of carbon dioxide were continually monitored. Marijuana smoking was associated with a significant increase in middle cerebral artery velocity. Although marijuana smoking was associated with increased pulse rate, the changes in blood velocity and pulse rate followed different time courses. Marijuana smoking was not associated with significant changes in blood pressure or end tidal carbon dioxide. PMID- 1420631 TI - The morphology of lipopigment in rat Purkinje neurons after chronic acetyl-L carnitine administration: a reduction in aging-related changes. AB - The aging-related accumulation of neuronal lipopigment is considered to be cellular debris from processes of renewal of cellular constituents, but it can also reflect cell damage and certain diseases. Acetyl-L-carnitine (AC) has been reported to reduce some morphological and behavioral associations of brain aging and the present study investigated the effects of 37 weeks of AC administration on lipopigment in rat Purkinje neurons. Lipopigment was identified by fluorescence microscopy and the area enclosed by an outline of each discrete region of lipopigment was measured. Acetyl-L-carnitine was associated with a significant (p = 0.05) reduction in the number of discrete lipopigment regions and there was a significant (p = 0.001) association of AC administration with numbers of lipopigment regions in various size categories. As AC administration was associated with a reduction in some of the aging-related morphological changes in lipopigment, this compound is a candidate for evaluation as a long term prophylactic agent for the adverse effects of cerebral aging. PMID- 1420632 TI - Laterality of motor activity during normal and disturbed sleep. PMID- 1420633 TI - Neuroendocrine dysfunction in Alzheimer's disease: results following TRH stimulation. PMID- 1420634 TI - Left ventricular enlargement associated with diagnostic outcome of schizophreniform disorder. PMID- 1420635 TI - The effect of a mental challenge test of plasma norepinephrine and cortisol in bulimia nervosa and in controls. PMID- 1420636 TI - Hallucination, dopamine and hypnotizability. PMID- 1420637 TI - Exercise and antidepressant serum levels. PMID- 1420638 TI - Herpes simplex mimicking functional psychosis. PMID- 1420639 TI - Neurodevelopmental model of schizophrenia. PMID- 1420640 TI - Schizophrenia research: the problem of controls. PMID- 1420641 TI - An olfactory-limbic model of multiple chemical sensitivity syndrome: possible relationships to kindling and affective spectrum disorders. AB - This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders. PMID- 1420642 TI - Platelet and whole blood serotonin content in depressed inpatients: correlations with acute and life-time psychopathology. AB - Platelet or whole blood serotonin content did not differ significantly in patients with major depression compared to healthy controls, but within the patient group, platelet serotonin levels correlated negatively with severity of depression (r = -0.49, p = 0.007). Levels were 39% lower in patients who had made a suicide attempt compared to nonattempter patients (47.2 +/- 27.3 versus 77.6 +/ 41.7 ng/10(8) platelets, p = 0.04). Conversely, comorbid borderline personality disorder (85.3 +/- 41.5 ng/10(8) platelets) was associated with 31% greater platelet serotonin content than nonborderline patients (58.9 +/- 31.1 ng/10(8) platelets) and 27% greater than healthy controls (62.4 +/- 19.8 ng/10(8) platelets). A pronounced seasonal variation in whole blood and platelet serotonin content was found in both patients and controls, largely due to lower levels in summer. Excluding cases tested in the summer abolished the statistically significant differences in patients with and without comorbid borderline personality disorder (BPD). Nevertheless, BPD attempters had lower serotonin levels than BPD nonattempters but higher serotonin levels than non-BPD attempters. Current hostility and a life-time history of aggression were positively correlated with platelet serotonin content (r = 0.44, p = 0.04 and r = 0.41, p = 0.06). This study provides evidence for an association between lower platelet serotonin content and depression and suicidal behavior, and association of higher platelet serotonin content and comorbid borderline personality disorder and behavior traits such as aggressivity. PMID- 1420643 TI - Clozapine in the treatment of dysphoric mania. AB - Seven patients with bipolar disorder, characterized by dysphoric mania with psychotic features and chronic disability, refractory to standard treatments and anticonvulsants, all showed marked symptomatic and functional improvement when given the atypical antipsychotic clozapine. During follow-up over 3-5 years, most of the patients sustained substantial gains in psychosocial function; and of the six patients remaining on clozapine, no further hospitalizations were needed. This remarkable improvement in a severely ill group of patients suggests that clozapine may have utility in the treatment of bipolar disorder as well as schizophrenia. PMID- 1420644 TI - Exercise tolerance in panic disorder patients. AB - Sixteen panic patients and fifteen normal controls performed submaximal exercise testing on a bicycle ergometer. Only one patient subject panicked. Biochemical, physiological, and psychological data showed similar exercise tolerance in both patients and controls. Exercise-induced distress and lactate increment do not appear to cause panic attacks. PMID- 1420645 TI - Alteration by a plasma factor of platelet aggregation and 5HT uptake in depression. PMID- 1420646 TI - The contribution of constructional accuracy and organizational strategy to nonverbal recall in schizophrenia and chronic alcoholism. AB - The Rey-Osterrieth complex figure was used to assess the separate influences of the constructional accuracy and the organizational strategy employed while copying the figure on the later, incidental recall of the figure. We tested a model, which hypothesized that subjects who copied the main framework of the figure holistically would be more likely to achieve good copy accuracy scores and to reproduce the figure more accurately at recall than subjects who used a piecemeal approach during copy. Subjects included 68 detoxified, chronic alcoholics (ALC), 28 patients with schizophrenia (SZ), and 69 normal control subjects (NCS). The results showed that the ALC and the SZ groups, on average, had lower accuracy and strategy scores at copy than did the NCS group, and furthermore, that the combined contributions of copy accuracy and copy strategy accounted for group differences at recall. A path analysis revealed that, for all three groups, copy strategy had a significant direct effect on copy accuracy. Moreover, copy accuracy and copy strategy made independent contributions to recall accuracy within the ALC and NCS groups; by contrast, within the SZ group, copy strategy made an independent contribution to recall performance but copy accuracy did not. These results suggest that (1) organizational strategy can influence constructional accuracy at both copy and recall; (2) copy accuracy and strategy have the potential to influence recall independently; and (3) the recall deficit in ALC could be attributed to abnormalities in both accuracy and strategy at copy, whereas in SZ it could be attributed only to strategy abnormalities. The deficits observed on the complex figure test in the ALC and SZ were primarily nonmnemonic and were related to ability in figure construction and organizational strategy. PMID- 1420648 TI - Effect of 12-hour infusion of naloxone on mood and cognition in normal male volunteers. AB - The effects of a 12-hour naloxone infusion on mood, cognition, and plasma cortisol levels were evaluated in eight normal subjects. The dosage used was a 10 mg dose plus 7 mg/hr (total = 94 mg). Naloxone induced a significant rise in serum cortisol and also induced cognitive impairment, as shown by increased choice reaction time, reduced ability to recall the order of letters and numbers, and reduced accuracy of spatial orientation. The rise in cortisol induced by naloxone was significantly correlated with the rise in the Profile of Mood Scale (POMS) score, indicative of dysphoria. Finally, performance on the spatial orientation task was highly negatively correlated with the peak POMS score after naloxone. From these data and previous studies it is concluded that opioid receptors of low sensitivity to naloxone may mediate a common mechanism regulating the pituitary-adrenal axis' mood, and cognitive function during stress. Personality traits may account for the large individual variability reported in previous studies. PMID- 1420647 TI - Sympathoadrenomedullary activity in the neuroleptic malignant syndrome. AB - Many clinical features of the neuroleptic malignant syndrome suggest that sympathetic nervous system hyperactivity is involved in the pathophysiology of this disorder. Only a few studies have examined levels of catecholamines or their metabolites in patients with NMS; results so far have been inconclusive. In the present study urinary catecholamine metabolites obtained during the course of NMS were studied with respect to frequently reported signs and symptoms of NMS. The principal findings are that (1) elevated urinary catecholamines and metabolites are a frequent but inconstant feature of NMS; (2) it is likely that sympathetic nervous system hyperactivity contributes to the picture of fulminant NMS; and (3) the role of the adrenal medulla in producing excess catecholamines during NMS is uncertain. PMID- 1420649 TI - Low plasma gamma-aminobutyric acid levels in male patients with depression. AB - Plasma levels of gamma-aminobutyric acid (GABA) were significantly lower in males with primary unipolar major depressive disorder than in healthy controls. Although the difference in means between control and symptomatic depressed patient groups was small, the distribution of plasma GABA in the depressed patients was markedly different from controls. Forty percent of depressed patients had plasma GABA levels below those of controls. Plasma GABA levels correlated positively with duration of illness, and negatively with age at onset of the mood disorder and the total Endogenomorphic Symptom Score on the Hamilton Rating Scale. Plasma GABA levels may be a biochemical marker of vulnerability to depression, as opposed to a consequence of the illness. A low GABA condition in depression fits and complements the prevailing biogenic amine hypotheses of depression. PMID- 1420650 TI - Asterixis induced by carbamazepine therapy. AB - There are very few reports about asterixis as a side effect of treatment with psychopharmacologic agents. In this report we present four patients treated with a combination of different psychotropic drugs, in whom asterixis was triggered either by adding carbamazepine (CBZ) to a treatment regimen, or by increasing its dosage. Neither dosage nor serum levels of CBZ were in a higher range. We consider asterixis to be an easily overlooked sign of neurotoxicity, which may occur even at low or moderate dosage levels, if certain drugs as lithium or clozapine are used in combination with CBZ. PMID- 1420651 TI - Carbamazepine addition in tricyclic antidepressant-resistant unipolar depression. PMID- 1420652 TI - Season-of-birth effect reveals the existence of etiologically different groups of schizophrenia. PMID- 1420653 TI - Lipids in psychological research: the last decade. AB - We review the recent literature examining lipid changes during stressful experiences, and the psychological and constitutional differences that influence lipid levels at rest and that may modulate lipid response to stress. Mild forms of chronic or episodic stress are apparently not associated with alterations in lipids and lipoproteins, but severe forms of real or perceived stress do appear to alter lipid levels. Acute laboratory stress is frequently associated with short-term alterations in lipids and lipoproteins, but the significance of these changes is unclear. Several individual characteristics, such as heightened neuroendocrine or autonomic reactivity to stressors, Type A component behavior, and other aspects of personality, appear to be associated with an atherogenic lipid profile. Stress may influence lipid concentrations and metabolism through a variety of physiological and behavioral mechanisms, but none have been clearly elucidated. Future research should concentrate on understanding these mechanisms. PMID- 1420654 TI - Serum lipids, neuroendocrine and cardiovascular responses to stress in healthy Type A men. AB - This study examined the relationship between serum lipid activity in healthy Type A men and cardiovascular and neuroendocrine responses to a behavioral stressor, mental arithmetic. Assessment of blood lipids included measures of total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), and serum triglycerides. Cardiovascular (blood pressure and heart rate) and neuroendocrine (epinephrine, norepinephrine and cortisol) responses were recorded before (rest), during (stress) and after (recovery) the mental arithmetic test. Diastolic blood pressure, mean arterial pressure and, to a lesser extent, systolic blood pressure levels at rest, during stress, and at recovery correlated positively with TC levels. In addition, both diastolic and mean arterial pressure were positively correlated with the ratio of TC to HDLC and with triglycerides during stress and recovery. Heart rate did not correlate with any lipid measure. Cardiovascular stress-reactivity calculated as change from rest to stress did not correlate significantly with any lipid measure. Plasma norepinephrine during stress correlated positively with triglycerides; a similar trend was observed for the TC/HDLC ratio. Plasma cortisol at rest and during stress correlated positively with the TC/HDLC ratio and serum triglycerides, and negatively with HDLC. Plasma norepinephrine reactivity calculated as change from rest to stress correlated negatively with HDLC and positively with triglycerides. In addition, cortisol reactivity was positively correlated with triglycerides. It is suggested that the mechanisms mediating Type A behavior and coronary heart disease may include increased cardiovascular and neuroendocrine responses as well as unfavorable lipid profiles. PMID- 1420655 TI - Time effects on event-related brain potentials and vigilance performance. AB - A review of the literature showed that in vigilance or oddball tasks, changes over time in event-related potentials (ERPs) and performance measures often seem to be unrelated, but a number of studies had some shortcomings. In the present study a visual vigilance experiment was carried out, in which single-trial ERPs and performance data of 40 males were obtained. A relationship between time trends in behavioral and ERP measures was found: an early P3 amplitude and response latency (RT) showed an inversely varying relation over time. Analysis of covariance showed that the two linear trends tap the same aspect of processing: both trends became insignificant when adjusted for common variance. A negative correlation between mean values of P3 amplitude and RT rather than for change scores has been observed in previous studies, but has been ignored in the literature. However, correlations with RT have also been reported for other ERP deflections. Although there were several correlations between mean scores, most time-induced changes in ERP parameters appeared to be unrelated to worsening performance, for which several explanations are advanced. The ERP results do not support the hypothesis that a decrement in performance is caused by increasing difficulty discriminating targets from nontargets. A gradual decline in effort or resources allocated to the task might be an alternative explanation of performance deterioration. However, an effort-hypothesis cannot easily be tested. Effort is often invoked post hoc, and has previously been associated with many ERP components. The relationship between ERPs and the signal detection measures "sensitivity" d' and "response bias" beta is discussed. PMID- 1420656 TI - [A prospective study on temporary and permanent sensation disorders after oral surgical measures in the lateral mandibular area]. AB - Postoperative disturbances of sensory nerve function after dentoalveolar surgery imply forensic problems. Also the indication of microsurgical reconstruction will be discussed in these cases as well. Both questions can only be seen on the background of data material concerning those nerve complications. Therefore a clinical prospective study on functional disturbances of the inferior alveolar as well as the lingual nerve after dentoalveolar surgery in 1.107 cases was undertaken. Concerning the inferior alveolar nerve 2.2% of temporary functional disturbances were assessed while 1.4% of temporary functional disturbances for lingual nerve were found. Complete restoration of sensory function was found three months postoperatively in 20% of these cases and six months postoperatively in the remaining patients. PMID- 1420657 TI - [Initial clinical experiences with the photodynamic therapy (PDT) of oral cavity carcinomas]. AB - Photodynamic therapy (PDT) is based on the selective accumulation of photosensitizing agents in tumor tissues. Activation of the photosensitizer with ligh of suitable wavelength leads to tumor destruction preserving healthy tissues. 13 carcinomas stage T1 and T2 of the oral cavity in men were treated. Necroses of a depth from 1.5 to 6 mm occurred regularly. Therefore photodynamic therapy seems to be suitable to treat small, superficial cancers of the oral cavity, especially, if the tumors are multilocated. PMID- 1420658 TI - [The use of the T-Scan system in occlusal diagnosis]. AB - The present study examines the T-Scan reproduction system used in occlusal diagnosis. The system represents a major technical innovation in functional diagnostics. Nevertheless, various aspects of it still require improvement. Amplifying or confirming the results of previous studies, the following observations are intended to indicate how the system might be improved, and how it can be reliably used at present: The reproduction afforded by the sensor as situated in the mouth is insufficient. Exact reproduction of the topography of the occlusal contacts is not possible. Reproducibility of the temporal sequence of the contacts is slight. The registering of dental functional movements can give rise to errors of interpretation. Threshold values for the registration of contact points in the system's pressure mode are uneven. The relative reproduction of different impressions is unreliable. Since in the system's pressure-mode early contacts cannot be distinguished from strong physiological contacts, in clinical practice the former must first be identified using the time mode. PMID- 1420659 TI - [The effect of the interocclusal space on temporomandibular recordings. A study with the use of the Stereognathograph PC]. AB - 1536 recordings of the condylar movement of 32 patients were made by means of the Stereognathograph PC. The test persons performed mediotrusive and protrusive movements. These movements were recorded with tooth contact and with increased interocclusal space, with and without the clinician's supportive guidance. The objective of the study was to analyse the effects of increased interocclusal space on the recording of the condylar path. Statistical evaluation showed that neither procedure has any real advantage over the other. Both, the occlusal tray as well as the paraocclusal tray may, depending on clinical situation of the ligaments, lead to erroneous recordings. The reproducibility of the recording of the condylar path is only slightly decreased by increased interocclusal space. Considering, however, the amount of work involved in each procedure, the occlusally fixated tray should probably be given preference, when there is no intention of recording occlusal guided movements. PMID- 1420660 TI - [Mandibular positions in complete dentures according to the calotte principle]. AB - A total of 37 patients was provided with complete dentures according to the calotte system. Two groups were formed with regard to the arrangement of the anterior teeth. After a mean period of wear amounting to 13 months different positions of the mandible were recorded in 21 patients under the guidance of a central bearing point and in occlusion. Patients with an arrangement of the anterior teeth free of interferences in excursive movements exhibited a significantly lower distance habitual occlusion/retruded position than subjects with an overlap limiting sagittal freedom. Therefore, an arrangement of the anterior teeth integrated into the calotte complex respectively free of interferences in eccentric positions is to be preferred. PMID- 1420661 TI - [Microbiological studies of self-disinfecting alginate impression materials]. AB - Using microbiologically experimental methods and observations corresponding to praxis the efficiency of the addition of antiseptics to alginate is evaluated. The addition of chlorhexidine to the alginate leads to a considerable reduction of the amounts of germs, but an one hundred percent disinfection of the alginates is not always performed. An influence of the alginate materials and the water quality on the antimicrobial efficacy of chlorhexidine has been proved. The always occurring contamination of the impression tray rules out a complete stopping of infection between the patient and the laboratory staff. PMID- 1420662 TI - [A clinico-histological study for the diagnosis and classification of spontaneous periodontal diseases in the dog]. AB - Using standardized investigation methods periodontal parameters were proved for diagnostic application of spontaneous periodontal diseases in dogs. The diseases are classified in gingivitis simplex, g. granulomatosa, g. ulcerosa, g. hyperplastica, g. desquamativa, juvenile periodontitis, rapidly progressive p. and chronic p. This proposal can be used for further investigations in experimental dentistry and for therapeutic purposes in veterinary dentistry. PMID- 1420663 TI - Tuberculin positivity among the homeless. PMID- 1420664 TI - Enhancing violence prevention in at-risk youth. PMID- 1420665 TI - Fitting the care to the patient. PMID- 1420666 TI - African-American women and abortion: a neglected history. AB - The history of African-American women's efforts to control their fertility is largely unknown. From slavery to the present, the growth rate of the African American population has been cut in half. Demographers and historians frequently attribute this change to external factors such as poverty, disease, and coerced birth control, rather than the deliberate agency of African-American women. This essay assembles a brief historical record of the ways African-American women have sought to control their fertility through the use of abortion and birth control. It also examines the activism of African-American women in the establishment of family planning clinics and in defense of abortion rights. PMID- 1420667 TI - Correlates of health insurance coverage: evidence from the Midwest. AB - The Midwest is often overlooked in national studies of health insurance status. We analyzed the economic and social characteristics of uninsured and underinsured individuals and households in a Midwestern state using both bivariate and multivariate techniques. As in much of the country, economic factors, particularly income and employment, were most significant in accounting for insurance coverage. Unexpectedly, rural and urban residents were equally likely to lack insurance. Results indicate that in rural areas, underinsurance may be a greater problem than uninsurance, and that income-based health insurance is more effective than employer-provided plans in reaching all Americans. PMID- 1420668 TI - The relationship between primary care and life chances. AB - Many researchers criticize clinical medicine for its failure to improve mortality rates. But in their critiques, few distinguish primary care from expensive, high technology specialized care. This research is concerned with the empirical relationship between the availability of health services resources (i.e., primary care, specialty care, hospital beds) and certain "life chances," as measured by overall and disease-specific mortality rates, and life expectancy. The model shows a significant direct association between primary care and favorable mortality outcomes, though the same does not hold true for variables such as hospital beds or physician specialists. There should be greater emphasis on prevention-oriented primary care as a mechanism for health improvement and cost control. PMID- 1420669 TI - Antibiotic-associated diarrhea. AB - Diarrhea is clearly one of the most common side effects encountered with antimicrobial treatment. Virtually all drugs with an antibacterial spectrum of activity have been implicated, although there are definite differences in associated incidence rates that appear to depend on spectrum of activity and pharmacokinetic properties. Most cases of antibiotic-associated diarrhea can be classified in two categories: cases in which Clostridium difficile is implicated and cases in which no putative agent or recognized pathophysiological mechanism is clearly established. This review is intended to provide management guidelines for patients with diarrhea that occurs in association with antibacterial agents. PMID- 1420670 TI - Neurobrucellosis: clinical and therapeutic features. AB - Eighteen patients with neurobrucellosis are described. Eleven patients had meningitis alone or with papilledema, optic neuropathy, or radiculopathy. Four patients had meningovascular complications manifested by stroke or intracerebral hemorrhage from a presumed mycotic aneurysm. Two patients had parenchymatous dysfunction, including a child who had a cerebellar syndrome without evidence of direct infection of the central nervous system. One patient presented with polyradiculopathy. Twelve of 16 patients had pleocytosis; none had cell counts greater than 419 x 10(6)/L. Most patients had hypoglycorrhachia and elevated levels of protein in the cerebrospinal fluid (CSF). Results of an agglutination test for Brucella in serum were positive for all patients. Six of 16 patients had positive blood cultures, and four of 14 had positive CSF cultures. Antimicrobial treatment included concurrent administration of two or more of the following drugs: streptomycin, tetracycline (or doxycycline), rifampin, and trimethoprim sulfamethoxazole. Eleven patients fully recovered. Five patients were left with residual neurological deficits. Four of these patients suffered permanent hearing loss, one of whom also had significant loss of vision in one eye. One elderly senile patient with meningovascular brucellosis remained in a vegetative state despite receiving antimicrobial therapy for 6 months. One patient died due to rupture of a mycotic aneurysm within 7 days of initiation of therapy. One other patient was treated after sustaining an intracerebral hemorrhage, but this patient's condition was diagnosed only after discharge. PMID- 1420671 TI - Atypical papulovesicular rash due to infection with Rickettsia conorii. AB - We present an unusual case of Rickettsia conorii infection that was associated with cutaneous papulovesicular lesions on a patient who had returned from the bushveld of South Africa. The lesions were diffusely scattered across the trunk, extremities, and both palms. Several recent reports have documented similar papulovesicular or pustulovesicular rashes that occurred on travelers returning from southern Africa. These rashes resemble the lesions of rickettsialpox. Evidence suggests that these atypical exanthems may be due to variant strains of R. conorii or to an unusual host response to infection with this organism; thus, infection with R. conorii should be included in the list of diseases that cause poxlike lesions. PMID- 1420672 TI - Rhinoceros' rhinorrhea: cause of an outbreak of infection due to airborne Mycobacterium bovis in zookeepers. AB - Seven of 24 zookeepers exposed to a Southern white rhinoceros infected with Mycobacterium bovis were presumably infected via aerosols generated in the cleaning of the barn for the rhinoceros. All demonstrated conversion by the intermediate-strength purified-protein-derivative skin test, but none had clinical illness. In certain occupational settings like zoos and abattoirs, exposure to M. bovis may be an occupational hazard, and routine periodic tuberculin screening should be performed. PMID- 1420673 TI - Comparison of mycobacterial lymphadenitis among persons infected with human immunodeficiency virus and seronegative controls. AB - Lymphadenitis is a common extrapulmonary manifestation of mycobacterial disease in persons with human immunodeficiency virus (HIV) infection. We compared the clinical, mycobacterial, and diagnostic characteristics of mycobacterial adenitis in 11 HIV-seropositive and 29 HIV-seronegative patients. Ninety-three percent of the HIV-seronegative patients and 54% of the HIV-seropositive patients were foreign-born. In contrast to the HIV-seronegative patients, seropositive patients were more likely to be febrile and have negative purified protein derivative skin tests and abnormal chest roentgenograms. Sputum samples were rarely diagnostic in either group. Mycobacterium tuberculosis was the most commonly isolated organism in both groups, although United States-born patients with HIV infection were more likely to be infected with nontuberculous mycobacteria. In contrast to results for seronegative patients, fine-needle aspiration was usually diagnostic in the HIV-seropositive population, especially in those at risk for M. tuberculosis infection. Similarly, the rate at which smears were positive for acid-fast bacilli was significantly higher in the HIV-seropositive group, a circumstance suggesting a higher burden of organisms in this population. Finally, although preceding opportunistic infections were uncommon in the HIV-seropositive group, both tuberculous and nontuberculous adenitis were associated with advanced immunosuppression. PMID- 1420674 TI - Antibiotic susceptibility profiles of 941 gram-negative bacteria isolated from septicemic patients throughout Canada. The Canadian Study Group. AB - The choice of antimicrobial therapy for the treatment of bacteremia is often empirical and based on the knowledge of antibiotic susceptibility profiles of the most common bacteria causing such infections. It therefore is crucial to survey the susceptibility of bacteria causing sepsis. This study examines the susceptibility profiles of 941 gram-negative bacteria, isolated from septic patients in 10 Canadian hospitals, to 28 antimicrobial agents. Among the isolates, 30 different species were represented; Escherichia coli dominated, representing 52.5% of isolates. More than 50% of all bacteria were resistant to ampicillin. Only 67% of the E. coli isolates were susceptible to ampicillin, while 30% of all strains were resistant to ticarcillin. Of the cephalosporins, ceftazidime and cefoperazone/sulbactam were the agents to which isolates were the most susceptible (90%). Only 51% of the E. coli strains were susceptible to cephalothin, while 91% were still susceptible to cefazolin. A total of 93% and 98% of the strains were susceptible to aztreonam and imipenem, respectively. Aminoglycosides were highly active against most isolates, in general in the following order: netilmicin greater than tobramycin greater than gentamicin greater than amikacin. Tobramycin was the most active against Pseudomonas aeruginosa. Nearly all isolates were susceptible to the quinolones. Tolerance (MBC/MIC ratio, greater than or equal to 32) was rarely observed. This survey of the susceptibility of gram-negative bacteria causing sepsis provides valuable information for implementing the chemotherapy for gram-negative septicemia and demonstrates that several older and newer agents, alone or in combination, can be used as adequate initial therapy for gram-negative sepsis in Canada. PMID- 1420675 TI - Epidemiology of blastomycosis in a region of high endemicity in north central Wisconsin. AB - The clinical and epidemiologic features of 73 patients with laboratory-confirmed blastomycosis who were identified over an 11-year period in North Central Wisconsin are presented. Pulmonary disease was the sole manifestation in 77% of patients. More than one-half of all patients had symptoms that included fever, cough, weight loss, night sweats, and pleuritic chest pain. Virtually all were previously healthy, and most did not have an outdoor occupation. However, 82% of these patients lived or had visited within 500 m of rivers or associated waterways. The majority experienced the onset of symptoms between December and April. The estimated mean annual incidence rate of infection for Vilas County was 40.4 cases per 100,000 persons, and that for the largest city in the county was 101.3 cases per 100,000 persons. Several areas with an exceptionally high incidence of the infection were observed. We suggest that, in regions where blastomycosis is hyperendemic, clinical disease is most often pulmonary and occurs in immunocompetent individuals and that residence near an ecological focus may be a greater risk factor for acquisition of blastomycosis than is occupation. PMID- 1420676 TI - Acute pubic osteomyelitis in athletes. AB - Three cases of pubic osteomyelitis in athletes are reported. The clinical presentation in each case was acute groin, hip, or perineal pain; fever; chills; inability to bear weight; and pubic symphysis tenderness. Since radiographic changes in the pubic bone can be delayed, a high index of suspicion is required by the clinician. Although Staphylococcus aureus is the dominant pathogen in pubic osteomyelitis, it is recommended that the diagnosis be established by culture of blood or pubic bone aspirate so that specific therapy can be instituted quickly. PMID- 1420677 TI - Phaeohyphomycosis due to Exophiala species: clinical spectrum of disease in humans. AB - Phaeohyphomycosis caused by Exophiala species is an unusual infection, but it has been reported with increasing frequency as immunosuppressive therapy has become more widespread and laboratory methods for diagnosis have improved. To our knowledge, the first case of subcutaneous phaeohyphomycosis due to Exophiala jeanselmei in a cardiac transplant patient is presented, and previously reported cases of exophiala infection are reviewed. This patient was successfully managed with surgical excision of the lesion and combination therapy with amphotericin B and 5-fluorocytosine. PMID- 1420678 TI - Unusual manifestations of Yersinia enterocolitica infections diagnosed using novel methods. AB - We report the cases of two patients who had infections due to Yersinia enterocolitica. The first patient exhibited chronic recurrent fever, hepatic and splenic granulomas, and bone marrow abnormalities, and the second patient presented with enterocolitis with leukocytoclastic vasculitis of the skin. Cultures and agglutination titers were negative. Indirect immunofluorescence techniques with use of serotype-specific antisera and antisera to Yersinia outer membrane proteins (Yops) were applied to biopsy specimens, and immunoblotting techniques for determining class-specific circulating antibodies to Yops were used for demonstrating these unusual manifestations of Y. enterocolitica infections. PMID- 1420679 TI - Concepts on the use of liposomal antimicrobial agents: applications for aminoglycosides. AB - Liposomes are microscopic lipid vesicles consisting of one or more concentric phospholipid bilayers enclosing discrete aqueous spaces. Liposomes provide an apparently nontoxic biological delivery system for hydrophobic and hydrophilic drugs. With few exceptions liposomal antimicrobial drugs are administered intravenously, although other routes have been investigated. Intravenously administered, conventionally prepared vesicles are rapidly cleared from the blood principally by phagocytic cells of the mononuclear phagocyte system (MPS), in particular by macrophages located in the liver (Kupffer's cells) and spleen. The expectation that liposomes would provide a new form of drug carrier capable of diverse physiological selectivity has not been realized. The low endocytotic capacity of many cell types and the inability of liposomes to transverse continuous vascular endothelia have prevented the active targeting of non-MPS tissues with liposomes. Despite their well-documented toxicity and the development of new antimicrobial classes, aminoglycosides continue to have an important antimicrobial role. The encapsulation of aminoglycosides into liposomes may reduce the toxicity associated with the multiple daily administration often required for patients with normal renal function. In addition, the encapsulation of aminoglycosides alters their pharmacokinetics, increases t1/2 and area under the curve, decreases Vd and Cpmax, and causes a shift in drug accumulation from the kidney to other organs, thus potentially reducing nephrotoxicity. Studies demonstrate improved outcome for intracellular infections treated with liposomal aminoglycosides vs. free aminoglycosides. Unresolved questions include what role liposomal aminoglycosides have in the treatment of extracellular infection and whether their sustained release action will promote resistance. PMID- 1420680 TI - Pyomyositis in North America: case reports and review. AB - We report two cases and review the characteristics of pyomyositis. The courses of patients who presented with pyomyositis at the Maricopa Medical Center (Phoenix) are detailed. Ninety-eight reported cases over the last 20 years in North America, found through a MEDLINE search, are summarized. Infection with the human immunodeficiency virus (HIV) may predispose the patient to pyomyositis. The onset is usually insidious with progression to large purulent collections and significant morbidity. The diagnosis is frequently suggested by findings of imaging studies. Staphylococcus aureus is responsible for most cases in tropical areas but is less frequently associated with cases in North America. Since infection with HIV predisposes patients to bacterial infections, pyomyositis will occur more frequently in this patient population. Increased awareness of the disease will improve management. Following aspiration or surgical drainage, therapy with broad-spectrum empirical antibiotics may be considered initially in the treatment of pyomyositis. PMID- 1420681 TI - Maternal-fetal transmission of human immunodeficiency virus: a review of possible routes and cellular mechanisms of infection. AB - The prevalence of human immunodeficiency virus (HIV) infections among children is increasing in a manner that closely follows the spread of the disease among women. Despite the fact that in utero transmission via the placenta is though to play a major role in the spread of HIV to the pediatric population, little is known about the timing, route(s), and cellular mechanisms by which maternal-fetal transmission occurs. This review attempts to use a developmental and cellular approach to assess the available clinical and laboratory data pertaining to maternal-fetal HIV transmission. While much of this review focuses on the role of the placenta, particularly the placental trophoblast, on the transmission of HIV, potential routes of infection during early development are also discussed. Clinical studies indicate that the placental trophoblast can be infected with HIV but have shed no light on how the virus gains entry to this tissue. While some laboratory studies confirm that trophoblast cells and placental macrophages can be infected with HIV in vitro, many studies are difficult to interpret because of inadequate characterization of the placental cells used. The role of CD4 in the infection of trophoblast remains controversial and clearly warrants a systematic examination. It is also apparent that viral tropism has not received enough attention and more studies using different strains of HIV are required. Thus, several basic questions remain to be answered before strategies to prevent maternal-fetal transmission of HIV can be developed. PMID- 1420682 TI - Tuberculosis of the breast as a presenting manifestation of AIDS. AB - Tuberculous infections of the breast are considered rare in the developed world. We describe a case of mammary tuberculosis in a woman who was not initially known to be seropositive for the human immunodeficiency virus (HIV) and who was thought to have a pyogenic breast abscess. This uncommon presentation of extrapulmonary tuberculosis as an AIDS-defining condition highlights the necessity for performing mycobacterial smears and cultures in such cases when patients are at risk for HIV infection. PMID- 1420683 TI - Central venous catheter sepsis caused by unusual Gordona (Rhodococcus species: identification with a digoxigenin-labeled rDNA probe. AB - We describe central line sepsis caused by Gordona (Rhodococcus) species in two patients, which complicated receipt of long-term total parenteral nutrition at home. Species identification was attempted by conventional biochemical analysis and analysis of polymorphisms in the ribosomal RNA genes with use of a digoxigenin-labeled rDNA probe. Using these techniques, we identified our first patient's isolate as Gordona terrae. The isolate from our second patient was biochemically atypical and could not be reliably matched to any of the recognized Gordona (Rhodococcus) species. To our knowledge, these patients are the first to have been reported with systemic infection caused by Gordona (Rhodococcus) species. The first patient's infection resolved after 6 weeks of intravenous therapy with vancomycin with the catheter left in situ; however, infection in the second patient required catheter removal for cure. These cases show that immunocompetent patients receiving long-term parenteral nutrition may develop central line infections with these unusual species of microorganisms. PMID- 1420684 TI - Isolated pulmonary aspergillar infection in cardiac transplant recipients: case report and review. AB - The optimal type and duration of antifungal therapy for localized aspergillosis in cardiac transplant recipients is unclear. We report the case of a patient who had persistent invasive pulmonary aspergillosis despite prolonged treatment with amphotericin B. A combined approach using antifungal therapy and surgery appears effective for localized pulmonary disease. Aspergillar infection in solid organ transplant recipients is reviewed. PMID- 1420685 TI - Biliary concentrations of fluconazole in a patient with candidal cholecystitis: case report. AB - A patient with acute cholecystitis due to Candida albicans and Candida parapsilosis was treated with a percutaneous cholecystostomy and daily intravenous fluconazole. Fluconazole levels in serum and bile were measured by gas chromatography. Fluconazole levels in the bile were equal to those in the blood for the first 8 hours after a dose and were slightly higher than serum levels after that. Bile levels after an oral dose of fluconazole were 15% higher than levels achieved after intravenous administration of the drug. The infection was cured after 2 weeks of treatment. This experience suggests that sufficient fluconazole is excreted in the bile to be effective for treatment of biliary infections due to susceptible yeasts. PMID- 1420686 TI - Meningitis due to Prototheca wickerhamii in a patient with AIDS. AB - The first documented case of algal meningitis due to Prototheca wickerhamii is reported in a patient with AIDS. The initial CSF culture yielded only Cryptococcus neoformans. P. wickerhamii was isolated on four subsequent lumbar punctures. The patient died, and at autopsy the alga was isolated from leptomeninges over the brain and about the spinal cord. Histologic sections from numerous locations of the brain revealed masses of cryptococci and prototheca. PMID- 1420687 TI - An unusual case of false-positive serology for the human immunodeficiency virus: report from the heterosexual HIV transmission study. AB - A man was found to have a repeatedly positive enzyme immunoassay (EIA) that was confirmed by a western blot with six positive bands. He was told that he was seropositive for the human immunodeficiency virus (HIV), but subsequent EIAs were negative and western blots were either negative or indeterminant. All other HIV related studies were unrevealing, and no explanation for the false-positive result was found. We have not absolutely eliminated the possibility of mislabeled specimens, but we believe this to be unlikely. The possibility, albeit infrequent, of concomitant false-positive EIAs and western blots should be kept in mind when formulating public policy with regard to HIV testing. PMID- 1420688 TI - Lymphocutaneous Nocardia brasiliensis infection acquired from a cat scratch: case report and review. AB - Nocardia brasiliensis is a bacterium that is most commonly found in the soil. Traumatic inoculation of N. brasiliensis into the skin is the most typical mode of acquisition of infection due to this organism. To the best of my knowledge, I report the first case of lymphocutaneous N. brasiliensis disease from a penetrating cat scratch of the skin, thereby establishing cats as vehicles for the transmission of this infection. Treatment with penicillin produced a rapid resolution of all signs and symptoms of infection. The efficacy of penicillin against the N. brasiliensis isolate recovered from this patient was highly unusual. In general, penicillin has limited therapeutic value since these organisms elaborate beta-lactamase. Sulfonamides remain the drugs of choice for the treatment of these infections. These soil-borne organisms are most likely carried on the claws of cats and may establish infection after percutaneous inoculation. A high index of suspicion for N. brasiliensis soft-tissue infection is required since a delayed or missed diagnosis may be associated with progressive local disease and/or widespread disseminated infection. PMID- 1420689 TI - Adenovirus pneumonia with severe sequelae in an immunocompetent adult. AB - Notable complications from adenovirus pneumonia in healthy adults are rare. We report a well-documented case of adenovirus type 3 infection in a previously well adult woman that resulted in severe pulmonary complications as well as self limited ocular, hepatic, and gastrointestinal abnormalities. PMID- 1420690 TI - Management of chronic urethral symptoms in men. AB - We describe 20 men who were referred because of chronic urogenital symptoms. They had been previously seen by zero to six physicians (mean, 1.8 physicians) and had been treated with zero to five courses of antimicrobial agents (mean, 2.4 courses) without relief of their symptoms. Results of physical examinations of all patients were normal. An extensive evaluation failed to reveal any objective evidence of urethral inflammation. Cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, and Trichomonas vaginalis were uniformly negative. No additional antimicrobial agents were prescribed. Data from follow-up questionnaires filled out by 10 of these men 5-28 months later (mean, 11.8 months) disclosed the disappearance of symptoms in three and the reduction of symptoms in four. Chronic urethral symptoms may occur in the absence of objective evidence of inflammation and infection with known urethral pathogens. Observation without antimicrobial therapy is the treatment of choice for such patients. PMID- 1420691 TI - Hepatobiliary infections caused by Haemophilus species. AB - Haemophilus species are rarely associated with hepatobiliary infections. We report a case of hepatic abscess caused by Haemophilus paraphrophilus and review the English-language literature for reports of infections of the liver and biliary system caused by Haemophilus species. Most patients identified had predisposing conditions. The pathogenesis of hepatobiliary infections due to Haemophilus species may involve ascending spread from the gastrointestinal tract or hematogenous seeding following oropharyngeal colonization. PMID- 1420692 TI - A two-year prospective, nationwide study to determine the epidemiology and impact of invasive childhood Haemophilus influenzae type b infection in Israel. The Israeli Pediatric Bacteremia and Meningitis Group. AB - Accurate data on invasive Haemophilus influenzae type b (Hib) disease from countries other than the United States and western Europe are limited, and none are available from the Middle East. We report the results of a nationwide prospective epidemiological study in Israel whose purpose was to provide a background for decisions regarding the need for Hib conjugate vaccinations. During the 2 study years, 344 patients less than 13 years of age with a positive blood or CSF culture for Hib were seen in 25 medical centers in which pediatric patients were hospitalized. The overall incidence of Hib disease was 34 per 100,000 persons less than 5 years old, an incidence in the range of those reported for western Europe. Twenty-two percent of patients were less than or equal to 6 months old, 69% were less than or equal to 12 months, 87% were less than or equal to 18 months, and 93% were less than or equal to 24 months. Thus, our findings represent a unique epidemiological pattern: the age distribution of our patients resembles that of immunologically compromised populations or of persons living in less-industrialized areas, but the incidence of disease is similar to that found in western Europe. In view of these data, the Israeli Ministry of Health decided to license conjugate vaccines for immunization of infants beginning at 2 months of age. PMID- 1420693 TI - AIDS enteropathy. AB - Chronic diarrhea is one of the hallmarks of advanced human immunodeficiency virus (HIV) disease. The symptoms of this complication are troublesome, have a significant impact on the patient's quality of life, and in severe cases can lead to extreme abnormalities in fluids and electrolytes and can even cause death. The workup for AIDS-associated diarrhea is often frustrating and frequently unrewarding. However, during the last 10 years, much has been learned about the causes of diarrhea; while treatment is still often ineffective, some advances have been made. Dr. John G. Bartlett and his colleagues in the Department of Medicine at Johns Hopkins University School of Medicine have been responsible for many of these advances. In this AIDS Commentary, these experts discuss recent advances that have enhanced our understanding of chronic diarrhea in HIV-infected persons and offer their recommendations for the most efficient and effective approach to managing these patients. PMID- 1420694 TI - Aspergillosis of the CNS presenting as aseptic meningitis. PMID- 1420695 TI - Vibrio parahaemolyticus septicemia in a patient with neutropenic leukemia. PMID- 1420696 TI - Immunity to measles and rubella in women infected with human immunodeficiency virus. PMID- 1420697 TI - Bite wounds and infection. PMID- 1420698 TI - Severe soft-tissue infection caused by Eikenella corrodens. PMID- 1420699 TI - Sporothrix schenckii meningitis in a patient with AIDS. PMID- 1420700 TI - Toxocaral visceral larva migrans after ingestion of raw lamb liver. PMID- 1420701 TI - Streptococcus zooepidemicus septic arthritis: case report and review of group C streptococcal arthritis. PMID- 1420702 TI - Penicillin-resistant pneumococcal vertebral osteomyelitis. PMID- 1420703 TI - Good response to antibiotic treatment of lung infection due to Rhodococcus equi in a patient infected with human immunodeficiency virus. PMID- 1420704 TI - Acinetobacter species: which do we mean? PMID- 1420705 TI - Aortic valve endocarditis due to Escherichia coli. PMID- 1420706 TI - Life-threatening Pseudomonas aeruginosa infections in patients with infection due to human immunodeficiency virus. PMID- 1420707 TI - Bacteremia due to vancomycin-resistant Enterococcus faecium of Van B phenotype during prophylaxis with vancomycin. PMID- 1420708 TI - Fatal intrauterine infection associated with Mycoplasma hominis. PMID- 1420709 TI - Evaluation of soft tissue response to a poly(urethane urea). AB - Variations in the performance of vascular prostheses constructed of polyurethanes, and some evidence which suggested that these variations could be due not to the properties of the polymer itself, but to differences in the cellular response to the various microstructures of porous polyurethanes require investigation. Experiments were performed to evaluate quantitatively the extent of the cell behaviour adjacent to a series of polyurethane samples. It was shown that, with Biomer, a polyurethane urea, the profile of cell behaviour as a function of distance from the implant surface and of time following implantation, the response of cells in general and macrophages in particular, varied considerably with different internal microstructure. This supports the suggestion that the cellular response to different structures and susceptibility to degradation are related. PMID- 1420710 TI - Seeding of enzymatically derived and subcultivated canine endothelial cells on fibrous polyurethane vascular prostheses. AB - Fibrous polyurethane (FPU) prostheses with or without fibronectin coating and gelatin impregnation and FPU prostheses with or without fibronectin coating were seeded with 4.8 x 10(5) subcultivated dog endothelial cells per cm2 prosthesis. Expanded polytetrafluoroethylene (ePTFE) prostheses with and without fibronectin coating served as controls. The numbers of cells retained on uncoated polyurethane prostheses were minimal but increased with fibronectin coating and/or gelatin impregnation. Adhering cells were predominantly round in shape and few cells were seen stretched over the prosthetic fibres. Optimum numbers of cells were found in prostheses impregnated with gelatin and coated with fibronectin, where almost all the cells were stretched forming a confluent monolayer. In ePTFE prostheses only minimal numbers of cells were retained but in the fibronectin-coated prostheses a high cell count was noted. Gelatin impregnated and fibronectin-coated FPU prostheses, as well as ePTFE prostheses coated with fibronectin, were additionally perfused in vitro after seeding under nearly physiological conditions for 1 h. Cells in the FPU prostheses were still present after perfusion, whereas all the cells in the ePTFE prostheses were lost from the inner surface. It is concluded that FPU prostheses impregnated with gelatin and coated with fibronectin are a suitable substrate for subcultivated endothelial cells to be seeded on. The cells remained at the surface even after 1 h in vitro perfusion with tissue culture medium under nearly physiological conditions. Further research including in vivo implantations is indicated. PMID- 1420711 TI - Microradiographic and histochemical evaluation of mineralization inhibition at the bone-alumina interface. AB - Microradiographic and histochemical tests were used to examine the behaviour of the bone tissue close to the alumina coating in cementless hip prostheses which were radiologically stable and explanted because of pain. The presence was detected of a decalcification stripe of the bone tissue with a thickness of about 300 microns, parallel to the prosthesis profile and in appearance not influenced by the roughness of the surface. This phenomenon was attributed to the presence of aluminium ions similarly to what happens in osteomalacic osteodystrophy in nephropathic dialysed patients. It was concluded that the phenomenon must be carefully considered because, in the long term, it could cause failure in the alumina coating. PMID- 1420712 TI - Surface characterization of microtextured silicone. AB - A set of microtextured silicone surfaces was manufactured using the technique of photolithography. The textures consist of a uniform array that imparts anisotropy to the surfaces. Processing the material required multiple steps which may have altered the surface characteristics. This project aimed to determine if a surface texture on implant grade silicone would affect the material characteristics. ESCA and contact angle studies revealed no measurable alteration of the surface chemistry or surface energy due to the texturing procedure or the presence of the texture. Both analytical techniques confirmed the material was silicone. The actual dimensions of the surface textures, size, spacing, depth and orientation of the textures were found to be close to the design values, using SEM and quantitative two- and three-dimensional profilometry. Standard 2D profilometry was not sufficient to characterize the surfaces, as a direct result of the uniformity of the arrays. A method of characterizing regular surface periodic structures is presented. PMID- 1420713 TI - Prevention of protein adsorption and platelet adhesion on surfaces by PEO/PPO/PEO triblock copolymers. AB - Fibrinogen adsorption and platelet adhesion on to dimethyldichlorosilane-treated glass and low-density polyethylene were examined. The surfaces were treated with poly(ethylene glycol) and poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymers (Pluronics). Poly(ethylene glycol) could not prevent platelet adhesion and activation, even when the bulk concentration for adsorption was increased to 10 mg/ml. Pluronics containing 30 propylene oxide residues could not prevent platelet adhesion and activation, although the number of ethylene oxide residues varied up to 76. However, Pluronics containing 56 propylene oxide residues inhibited platelet adhesion and activation, even though the number of ethylene oxide residues was as small as 19. Fibrinogen adsorption on the Pluronic-coated surfaces was reduced by more than 95% compared to the adsorption on control surfaces. The ability of Pluronics to prevent platelet adhesion and activation was mainly dependent on the number of propylene oxide residues, rather than the number of ethylene oxide residues. The large number of propylene oxide residues was expected to result in tight interaction with hydrophobic dimethyldichlorosilane-treated glass and low-density polyethylene surfaces and thus the tight anchoring of Pluronics to the surfaces. The presence of 19 ethylene oxide residues in the hydrophilic poly(ethylene oxide) chains was sufficient to repel fibrinogen and platelets by the mechanism of steric repulsion. PMID- 1420714 TI - Humoral responses to type I collagen after surgical curettage procedures employing bovine collagen implants. AB - Freeze-dried bovine type I collagen was implanted into periodontally diseased sites of 11 patients in an effort to repair the affected site. Peripheral blood samples taken at 0, 6 and 12 wk were assayed for antibody to human and bovine collagen using an enzyme-linked immunosorbent assay and compared with samples from 9 control subjects. Antibody levels to both human and bovine collagen, which were present at significantly higher levels in the patients at 0 wk than in the control subjects (P less than 0.01 for human and bovine), were significantly lower at 6 wk than at zero time (P less than 0.05 and P less than 0.01 for human and bovine collagens, respectively). At 12 wk post-implantation, the antibody level to human collagen still remained significantly lower (P less than 0.05) than zero time levels but not in respect of the antibody to bovine collagen. PMID- 1420715 TI - In vitro resistance of artificial connective tissues to human bile and pancreatic juice. AB - The resistance of connective tissue generated from elastin, placenta extracts and human collagen was tested by in vitro incubation with bile and pancreatic juice to investigate the potential use in human digestive surgery. The resistance, determined by macroscopical and microscopical examinations, has been directly compared to those of bovine collagen matrices (Spongel, Pangen, Helistat, Translagen). Only the compact and cross-linked human collagen patch resisted both bile and pancreatic juice. All other biomaterials tested dissolved either in bile or in pancreatic juice. The in vivo behaviour of this new human collagen matrix and its involvement in gastrointestinal wound healing must now be investigated. PMID- 1420716 TI - Immobilization of alpha-amylase into photographic gelatin by chemical cross linking. AB - alpha-Amylase was immobilized into photographic gelatin by chemical cross-linking with chromium (III) acetate and chromium (III) sulphate. Cellulose triacetate film strips, enabled simple handling when coated with an alpha-amylase-gelatin mixture, accomplishing a high degree of durability during consecutive immersions into reaction media. The optimum conditions for pH, substrate concentration, temperature, incubation time and storing conditions of free and immobilized alpha amylase were determined. The effect of use number on activity and the effect of resting on reuse number were also determined. Photographic gelatin was found to be a very efficient natural polymer, due to its extraordinary diffusion characteristics for immobilization as a carrier. PMID- 1420717 TI - Principle and investigation of the bioadhesion mechanism of solid dosage forms. AB - The development of bioadhesive tablets requires a good knowledge of their adhesion mechanism and the possibility of using an accurate in vitro evaluation technique. The bioadhesion mechanism is not basically different from the general adhesion mechanism, but it is necessary to take into account the biological nature of at least one of the two substrates involved in the process. The hydrated joint created at the molecular interface, resulting from the inter penetration of the polymeric chains of the mucin and the bioadhesive product, is especially interesting, because its viscoelastic properties make it a damping device for the stresses transmitted to the bioadhesive surface. PMID- 1420718 TI - Characterization of surgical suture materials using dynamic mechanical analysis. AB - Dynamic mechanical analysis (DMA) has been used to characterize the viscoelastic properties of four suture materials, Prolene, Maxon, Vicryl and silk. The technique identified the main transitions for the sutures and frequency multiplexing was used to define the variation of modulus with time. The monofilament Prolene has a beta transition and the monofilament Maxon has an alpha transition close to room temperature, indicating that both materials exhibit a change in stiffness with time. The alpha transitions (Tgs) of silk and Vicryl occur at temperatures significantly above room temperature and frequency multiplexing data indicate that both materials exhibit stable moduli with respect to time at room temperature. Determination of the viscoelastic behaviour through DMS appears to be very useful in predicting the performance of suture materials. PMID- 1420719 TI - Bone cell interactions with a granular glass-ionomer bone substitute material: in vivo and in vitro culture models. AB - The interface between bone and a synthetic bone substitute constructed from glass ionomer cement (ionomeric microimplant) was studied in diffusion chambers implanted in a primate baboon model (Papio ursinus) and in in vitro primary bone organ cultures derived from neonate rat calvaria. In both models osteoblast-like cells colonized the surface of the implant producing a collagenous extracellular matrix. An electron-dense bonding zone similar to that reported for hydroxyapatite and titanium was seen in both models but was a more constant feature of the tissue/implant interface in calvarial culture. PMID- 1420720 TI - Further observations on high impact strength denture-base materials. AB - Previous studies have shown that high impact strength can be conferred on denture base poly(methyl methacrylate) polymers by modification with acrylic-terminated butadiene-styrene block copolymers, and that the acrylic end-group was necessary for effective reinforcement. It is now shown that, by solvent extraction studies, grafting of the copolymer occurs both with acrylic-terminated and non-terminated block copolymers. It is therefore concluded that the mode of grafting is different, and some possible mechanisms are discussed. PMID- 1420721 TI - Soft tissue reaction to de novo plaque formation on implants and teeth. An experimental study in the dog. AB - The aim of the present investigation was to assess the effect of de novo plaque formation on the gingiva and masticatory mucosa around teeth and implants. The study was performed in 5 beagle dogs which at the initiation of the experiment were 15 months old. During a preparatory period, the mandibular right premolars were extracted, 3 fixtures installed, abutment connection performed and a 4-month period of plaque control completed. A clinical examination was performed and biopsies of the second mandibular premolar (P2) and the contralateral implant site (2P) were sampled. The dogs were allowed to form plaque during a period of 3 weeks. The clinical examination was repeated and biopsies harvested from the 2 remaining implants and the contralateral tooth sites. The tissue samples were prepared for histometric and morphometric analysis. Both the masticatory mucosa at implants and the gingiva responded to de novo plaque formation with the development of an inflammatory lesion. The size as well as the composition of the lesions in the 2 tissues had many features in common. It was concluded that the mucosa around implants and the gingiva around teeth had a similar potential to respond to early plaque formation. PMID- 1420722 TI - Functional adaptation to full-arch fixed prosthesis supported by osseointegrated implants in the edentulous mandible. AB - The objective of the present study was to assess possible adaptive functional changes in the masticatory system after insertion of fixed prostheses supported by osseointegrated implants in the edentulous mandible. Registrations of mandibular movement characteristics and maximal biteforce were performed at insertion and after 1 week, 3 months and 1 year after connection. The duration of the opening and closing phase decreased and maximal biteforce increased significantly (p < or = 0.05-0.001) from connection of the prostheses to the annual check-up. However, the process of functional adaptation implied 2 identified stages. An immediate phase that occurred within the 1st week, probably due to altered impact from mechano-sensitive receptors and a later more time dependent phase, based on learning and new cortical engrams. Accordingly, the process of adaptation will continue over a long period of time. PMID- 1420723 TI - Quantitative digital subtraction radiography for the assessment of peri-implant bone change. AB - The purpose of this study was to develop a digital subtraction technique to assess peri-implant bone change. The method uses subtraction radiography to enhance visualization of the area of change that has occurred between radiographic examinations, and superimposes the area of change on the original radiographs. Furthermore, a reference wedge allows calculation of the mass of the lesion. The method was validated using 21 small bony chips placed on 3 different skulls prior to the first radiograph. The chips were removed, a second radiograph taken, and the images subtracted. A morphologic method was used to isolate the lesion and the change in bone mass calculated. Overall, there was excellent correlation between the calculated lesion mass (mg) and actual lesion mass (r2 > 0.90). The utility of the method was demonstrated using a case that experienced implant failure. These data indicate that quantitative digital subtraction radiography may be of value in measuring peri-implant bone change in root form implants. PMID- 1420724 TI - A semi-automated computer-assisted method for measuring bone loss adjacent to dental implants. AB - The purpose of this study was to develop a repeatable method for measurement of bone support around root form and blade implants suitable for use in high-quality but unstandardized radiographs. 10 phantoms were fabricated to simulate progressive osseous defects around implants. Radiographs were taken in triplicate and digitized. Specialized software was written which placed a grid of known dimensions over the implant so that the top and the bottom of the grid were at the neck and the base of the implant, respectively. The investigators selected the edge of the bone at each point where the grid intersected the implant and the software automatically detected the implant edge. The software also outlined and displayed the defect on the computer monitor. Measurements were performed 5 times and the standard deviation was taken as a measure of the repeatability of the method. Repeatability for blades and root forms was 0.19 +/- 0.07 mm and 0.08 +/- 0.03 mm, respectively. There was no significant difference in the ability to measure bone loss in the blade versus the root form (p = 0.17, NS). These results indicate that this semi-automated computer-assisted method for measuring bone loss around implants is repeatable and may be of value for clinical trials using either root form or blade implants. PMID- 1420725 TI - A comparative study of the clinical efficacy of Screw Vent implants versus Branemark fixtures, installed in a periodontal clinic. AB - The clinical success of 85 Screw Vent and 107 Branemark implants, consecutively installed in a private periodontal clinic under the same conditions and by the same operator, is compared. Mobile implants were removed and considered as failures. Intra-oral radiographs were assessed for the presence of peri-implant radiolucencies and for analysis of bone loss after functional loading. 85 Screw Vent implants were installed in 31 patients. Of 23 implants installed in 9 mandibles, none failed after 16.8 (range 12-25) months of function. Of 62 Screw Vent implants installed in 23 maxillae, 6 failed at abutment connection, 1 failed after 2 months and 2 after 13 months of function. The absolute failure rate after 13.2 (range 6-24) months was 9/62. Mean loss of bone was 1.47 mm (-1.0- +4) after 12 months of functional loading. 107 Branemark fixtures were installed in 25 patients. Of 51 fixtures inserted in 12 mandibles, none failed; of 56 fixtures installed in 13 maxillae 1 failed before and 2 failed during abutment connection. The absolute failure is 3/56. All remaining fixtures were immobile after loading. 13 fixtures were more than 6 months in function. Only short-term comparison between both systems is possible because the observation time is longer for the Screw Vent implants. In the 1st year, only 1 implant system was available to the periodontist. Short-term comparison reveals 11.3% versus 5.3% of cumulative failure after 6 months for the Screw Vent and Branemark implants, respectively. The results indicate that clinical efficacy is as effectively obtained with Screw Vent as with Branemark implants in the mandible. The outcome of treatment with Screw Vent implants in the maxilla seems less predictable. PMID- 1420726 TI - Treatment of an early implant failure according to the principles of guided tissue regeneration (GTR). AB - The present case report demonstrates the application of guided tissue regeneration (GTR) in combination with antimicrobial therapy for the treatment of an early implant failure. This treatment approach both prevented further loss of bone as well as led to the regeneration of lost bone. By means of color-converted digital subtraction images, remodelling of the tissues adjacent to the defect was documented as early as one month postsurgically. The images demonstrated "bone fill" in the apical portion of the defect and resorptive changes at the bone crest. This case report demonstrates that combined regenerative and antimicrobial therapy may be a successful treatment approach restoring osseointegration of dental implants following loss of bone due to infection. Continuously increasing bone-fill inside the defect was documented when comparing the radiograph obtained immediately before the GTR procedure and at months 1, 2, 4, 5 and 6 of the healing period, respectively. Clinical measurement obtained at the time of the surgery and at the time of the membrane removal confirmed the radiographic evidence of bone-fill by demonstrating new tissue resistant to probing in close contact to the implant surface at the site of the previous defect. Antimicrobial therapy included an antibiotic regimen during the 1st month of healing as well as topical rinses with an antiseptic (chlorhexidine) over the entire healing period of 6 months. As a result of this treatment approach, the implant was saved and could be used as an abutment for a bridge reconstruction. PMID- 1420727 TI - Experimental breakdown of peri-implant and periodontal tissues. A study in the beagle dog. AB - The objective of the present experiment was to study lesions in the peri-implant and periodontal tissues resulting from ligature placement and subgingival plaque formation. The experiment was performed in 5 beagle dogs which at the start of the study were about 15 months old. They were given a diet which allowed gross plaque formation. The mandibular right premolars were extracted, 3 fixtures (a.m. Branemark) installed and abutment connection performed. Towards the end of a 6 month plaque control period, a clinical and radiographic examination was performed. Ligatures were placed in a subgingival position at 2 of the implants and the contralateral premolars. Plaque was allowed to accumulate. After 6 weeks, the ligatures were removed. 1 month later, the clinical and radiographical examination was repeated and samples from the subgingival microbiota obtained. Biopsies from the teeth and implant sites were harvested and processed for histometric and morphometric analyses. The results from the clinical and histological examinations revealed that: (i) clinical and radiographic signs of tissue destruction were more pronounced at implants than at teeth; (ii) the size of the soft tissue lesion was larger at implants than at teeth; (iii) the lesion at implants but not at teeth extended into the bone marrow. PMID- 1420728 TI - Programmed cell death: concept, mechanism and control. AB - Programmed cell death or apoptosis occurs under physiological conditions as a result of physiological effectors. It is a relatively slower process and requires active participation of the cell in the suicidal mechanism. Apoptosis is controlled by precise intrinsic genetic programme and may be induced by almost all those stimuli causing necrosis. The role played by the intensity in determining the death process and the underlying mechanism is imperfectly understood. Morphologically apoptotic cells appear as small condensed body. The chromatin is dense and fragmented, packed into compact membrane-bound bodies together with randomly distributed cell organelles. The plasma membrane loses its characteristic architecture and shows extensive blebbing. It buds off projections so that the whole cell may split into several membrane-bound apoptotic bodies. Significant chemical changes take place in the plasma membrane. This helps in recognition of the apoptotic bodies by phagocytes. At this moment it is unclear if all cells can undergo apoptosis or it is a characteristic of only some tissues which are predisposed to apoptotic death being directly under the control of hormones or growth factors. Experimental studies aimed at comparison of induction of apoptosis in cells of different origin are warranted to elucidate this point. Biochemically a pre-commitment step for induction of death programmation through macromolecular synthesis is essential for most systems. The double-stranded linker DNA between nucleosomes is cleaved at regular inter-nucleosomal sites through the action of a Ca2+, Mg(2+)-sensitive neutral endonuclease. Zinc is a potent inhibitor of the enzyme. Calcium probably plays a key controlling role in activation of the enzyme since prevention of Ca2+ increase prevents endonuclease activation. It is becoming evident that signal transduction through appropriate receptors control the Ca2+ flux in the cells. Most apoptotic cells require synthesis of RNA and proteins. Delay or abrogation of apoptosis by inhibition of macromolecular synthesis is well known. The dying cells show high mRNA levels for several enzymes. Several degradative enzymes become active. Regulatory proteins maintain control over the apoptotic cascade. At the molecular level, search has been initiated for the mammalian equivalents of the cell death (ced) gene. Activation of several specific genes is indicated. Specific expression of cell death-associated gene products (e.g. TRPM-2/SGP-2) has been reported in several unrelated apoptotic cell systems. Sequential induction of c-fos, c-myc and 70 kDa heat shock protein is reported. Studies demonstrate that certain genes must remain in a transcriptionally active demethylated state during programmed cell death. Recent evidences clearly indicate that apoptosis may be positively or negatively modulated by certain genes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1420729 TI - Cell adhesion molecules: a unifying approach to topographic biology. AB - Cell adhesion molecules are pivotal to the development and maintenance of tissue structure in metazoan organisms. In mammals, several families of proteins are involved in cell-cell and cell-matrix adhesion. The cadherins are homophilic, primary CAMs, involved in the establishment of boundaries between cell collectives early in embryogenesis. The Ig gene superfamily have diversified widely, with homophilic and heterophilic CAMs and antigen recognition molecules amongst the members. The Integrin family play an important role in binding to extracellular matrix, as well as counter-receptors on the surface of other cells. The Selectin family and HCAM are carbohydrate-binding proteins, and play a prominent role in the circulation of lymphocytes and neoplastic cells. CAMs are fundamental to development of tissue structure in metazoan organisms. Cellular differentiation dictates adherence to a specific microenvironment, through the pattern of surface CAM expression. Conversely, CAM binding can affect gene expression within the cell itself. Cell differentiation and cell adhesion are interdependent processes. In the adult, CAM are crucial to tissue maintenance. Cells frequently change their adhesive properties in response to physiological or pathological processes. The integrity of the vascular system is maintained by circulating platelets which are capable of rapid upregulation of cell adhesion and profound changes in metabolism, on contact with subendothelial matrix. Both endothelial cells and neutrophils undergo changes in CAM expression in response to inflammatory mediators, permitting rapid and appropriate recruitment of phagocytes to damaged tissue. Tissue repair is dependent on phenotypic changes in normally static cells, allowing increased motility and replication. The immune system requires constitutive cells to undergo multiple complex adhesion and detachment events over short periods of time, and is capable of discriminating normal self from aberrant-self or non-self, through antigen specific recognition and adhesion molecules. The pathophysiology of processes such as infection and neoplasia are profoundly affected by cellular CAM expression. CAMs and related molecules are fundamental to the development, maintenance and surveillance of tissue structure. PMID- 1420730 TI - Endothelium-dependent responses of cerebral arterioles to adenosine 5' diphosphate. AB - The goal of this study was to determine the role of endothelium-derived relaxing factor (EDRF) in dilatation of cerebral arterioles in response to adenosine 5' diphosphate (ADP). Using intravital microscopy, we measured the diameters of pial arterioles in vivo in rats during superfusion with ADP, acetylcholine and nitroglycerin before and during topical application of inhibitors of nitric oxide synthesis (NG-monomethyl-L-arginine; L-NMMA and NW-nitro-L-arginine; L-NNA). Prior to suffusion with L-NMMA and L-NNA, ADP (10 and 100 microM), acetylcholine (0.1 and 1.0 microM), and nitroglycerin (1.0 and 10 microM) produced dose-related increases in the diameter of pial arterioles. Following application of L-NMMA (1.0 and 10 microM) and L-NNA (0.1 and 1.0 microM), dilatation of cerebral arterioles in response to ADP was significantly inhibited. In addition, L-NMMA and L-NNA significantly inhibited dilatation of cerebral arterioles in response to acetylcholine, but did not alter vasodilatation in response to nitroglycerin. Thus, our findings suggest that ADP dilates cerebral arterioles via the production of nitric oxide, or a nitric-oxide-containing compound. PMID- 1420731 TI - Endothelium function is protected by albumin and flow-induced constriction is independent of endothelium and tone in isolated rabbit femoral artery. AB - To investigate the preservation of endothelial function, we perfused two segments of one rabbit femoral artery (n = 8) in a pressure myograph in parallel, both with Tyrode, but one with 0.6% albumin added. The change in the outer diameter of the vessels [preconstricted with norepinephrine (NE) to 70%] in response to acetylcholine as an indicator of the endothelial function, was repeatedly measured over 5 h after the equilibration. The difference between the acetylcholine responses of the two vessel segments was significant (p < 0.05) after a perfusion period of 4 h. We also investigated whether flow-induced constriction is dependent on (1) the presence of endothelium and (2) the level of preconstriction. We therefore perfused segments of rabbit femoral arteries (n = 5) with Tyrode with 0.6% albumin. If acetylcholine-induced dilatation was present, a flow-diameter relation was determined at two constriction levels: about 60% (high) and 90% (low) of the passive outer diameter. Both determinations were repeated after mechanical endothelium removal (checked functionally and histologically). A similar decrease in diameter (about 7%) with an increase in flow ranging from 0 to 1,330 microliters/min was found in all conditions. We conclude that the addition of (0.6%) albumin protects endothelial function in the rabbit femoral artery when perfused in the low-flow range for a period longer than 4 h. We also found that flow-dependent constriction is neither influenced by the presence of the endothelium nor by the level of tone induced with NE. PMID- 1420732 TI - Synthesis of TGF-beta 1 by vascular endothelial cells is correlated with cell spreading. AB - Cultured vascular endothelial cells (ECs) secrete transforming growth factor beta (TGF-beta) which stimulates intimal smooth muscle cells to synthesize increased amounts of lipoprotein-binding proteoglycans. We report here that the amount of TGF-beta 1 synthesized by ECs is correlated with EC density and cell spreading. ECs cultured at low density synthesized and secreted 2- to 3-fold more TGF-beta, measured by the Mink lung cell assay, than intermediate and high density cultures, and this increase in secreted protein was matched by a corresponding increase in mRNA for TGF-beta 1 measured by Northern hybridization using a [32P] labeled cDNA probe for TGF-beta 1. TGF-beta 1 mRNA was detected in individual cells by in situ hybridization with the cDNA probe labeled with [35S] and with a [35S]-labeled 30-mer antisense oligonucleotide. In situ mRNA levels did not relate to cell density per se but to cell area. The larger the area of substratum covered, the more mRNA per cell, irrespective of cell density. For cell areas in the range 500-1,200 microns 2, a doubling of cell area resulted in an approximately 3-fold increase in mRNA. Cells cultured at low density had a larger mean cell area than cells cultured at higher densities, and this increased area was sufficient to account for the increased TGF-beta 1 mRNA levels found for the low density cultures by Northern hybridization. Despite variations in cell area, cell volumes did not change significantly with cell density.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420733 TI - Review article: metabolic consequences of long-term inhibition of acid secretion by omeprazole. AB - Metabolic sequelae of profound and long-lasting inhibition of gastric acid secretion by omeprazole have largely been neglected. Data from long-term studies suggest that vitamin B12 stores decrease slightly over several years, although this was not clinically relevant within the first 4 years of therapy. Additionally, it cannot be completely ruled out that patients with an increased iron demand may develop iron deficiency, but data available at present do not provide any evidence that iron malabsorption is to be expected under normal conditions. Protein homeostasis and calcium metabolism seem to be unaffected by long-term omeprazole therapy. Based upon present experience, serum cobalamin concentration should be monitored in patients undergoing omeprazole therapy for several years. PMID- 1420734 TI - Effect of potassium chloride on gastric acid secretion and gastrin release in humans. AB - The effect of potassium chloride on gastric acid secretion and gastrin release was studied in 6 healthy human beings. On 3 separate days and in random order, subjects received an intragastric infusion of 0.5 L of a glucose-saline solution to which had been added 40 mmol KCl, 40 mmol NaCl, or no additional salts. All test solutions stimulated acid secretion and gastrin release to a similar degree. While potassium ions play a critical role in acid secretion by parietal cells (via the H+, K(+)-ATPase), KCl administered into the gastric lumen at a concentration of 80 mmol/L has no effect on acid secretion in man. PMID- 1420735 TI - Experience with 'triple' anti-Helicobacter pylori eradication therapy: side effects and the importance of testing the pre-treatment bacterial isolate for metronidazole resistance. AB - At the 1990 World Congresses of Gastroenterology, the Working Party on Helicobacter pylori (H. pylori) recommended that, in suitable patients, the bacterium should be eradicated using a therapeutic regimen comprising a bismuth salt, tetracycline and metronidazole for two weeks. We have treated 40 patients infected with H. pylori with 'triple' therapy consisting of 120 mg tripotassium dicitrato bismuthate q.d.s., 500 mg tetracycline q.d.s. and 400 mg metronidazole t.d.s. for two weeks. The success rate, in terms of bacterial eradication, was 19/21 (90.5%) in patients with metronidazole-sensitive organisms, compared with only 6/19 (31.6%) in patients whose H. pylori were resistant to metronidazole (P less than 0.01). Side effects, particularly diarrhoea and vomiting/nausea, were common: 23/40 patients reported such symptoms during the 14-day course of therapy. Fifteen of these 23 patients completed the entire 14-day course, although suffering from significant side effects, while the remaining eight patients had to discontinue the treatment because side effects became intolerable. If a form of triple therapy is going to be widely used to eradicate H. pylori infection, the regimen will have to be simpler, shorter, produce fewer side effects and be more effective in patients with metronidazole-resistant bacteria. PMID- 1420736 TI - Co-administration of misoprostol or ranitidine with indomethacin: effects on pharmacokinetics, abdominal symptoms and bowel habit. AB - This three-way randomized crossover study in 18 healthy male volunteers compared the pharmacokinetics of 50 mg indomethacin b.d. during concomitant twice daily dosing with 400 micrograms misoprostol, 150 mg ranitidine or placebo. Plasma indomethacin concentrations were determined by HPLC assay of samples collected over 12 h after the first dose, and over 14 h after the last dose on Day 8 of each dosing period. A daily diary of bowel habits, and the occurrence and severity of abdominal symptoms, was kept by each subject throughout the study. Statistical comparisons were made by analysis of variance. In the presence of misoprostol there was a 13% decrease in the area under the plasma concentration time curve of indomethacin over one dosing interval on Day 1 (P less than 0.01), and at steady state there was a 24% decrease in the maximum plasma concentration (P less than 0.02). The pharmacokinetics of indomethacin were not affected by co administration of ranitidine. Accumulation of indomethacin after repeated oral dosing was not significantly altered by the co-administration of either misoprostol or ranitidine. The frequency and severity of abdominal symptoms was significantly increased (P less than 0.01) during misoprostol dosing, compared with either ranitidine or placebo plus indomethacin. When the dosing phase (Days 1-8) was compared with the washout phase (Days 9-15) in each period, misoprostol, but not ranitidine or placebo, plus indomethacin resulted in an increase (P less than 0.001) in abdominal symptom severity, frequency of bowel motions and a decrease in faecal consistency. PMID- 1420737 TI - An artificial stomach-duodenum model for the in-vitro evaluation of antacids. AB - To improve the dynamic in-vitro evaluation of the effects of antacids, we have developed the 'artificial stomach' model by adding a 'duodenal reservoir' to receive the gastric emptying flux and simulated bicarbonate secretion, thus constituting an 'artificial stomach-duodenum' model. With this model we measured antacid-induced resistance to gastric acidification, and simultaneously evaluated the effect of antacid activity on the duodenal milieu. The model also permitted evaluation of the antacid effects of proteins (as natural antacids), and of drugs containing aluminium phosphate, alone or combined with magnesium oxide, or aluminium and magnesium hydroxides. At the gastric site, these drugs, as well as the proteins (that is, meat extract), induced a strong resistance to acidification due to the gastric emptying flux and to antacid composition. At the duodenal site, the decrease of the acid load penetrating into the duodenum varied, depending on the efficacy of gastric antacid activity. Duodenal pH was related to the equilibrium between bicarbonate secretion and the emptying of acid load. Proteins and aluminium phosphate induced the same duodenal pH as in the control tests without antacids, but magnesium-containing antacids increased it, thus decreasing bicarbonate consumption. The antacid mechanisms within the stomach, and the fate of antacids in the duodenal milieu, might explain the variation in duodenal pH in response to antacid administration. PMID- 1420738 TI - Oral pharmacokinetics of cyclosporin in patients with primary biliary cirrhosis and patients with skin diseases. AB - The pharmacokinetics of cyclosporin after oral administration were studied in seven patients with non-end stage primary biliary cirrhosis (PBC) without previous cyclosporin treatment (Group I), a control group of nine patients with skin diseases (mainly psoriasis; Group II) and six patients with PBC after prolonged cyclosporin treatment (Group III). Whole blood concentrations of cyclosporin were measured using a non-specific (N) radioimmunoassay (RIA) and--in a majority of the cases--also by a RIA specific (S) for the parent drug. No difference in cyclosporin absorption was observed between patients with PBC and those with a skin disease. The mean values for the area under the blood concentration-time curve for the first 6 h after the test dose (AUC0-6) and the maximal blood concentrations (Cmax) were significantly higher for Group I compared with Group II patients (P = 0.007 and 0.03, respectively), but the time to maximal blood concentrations (tc,max) did not differ. There was a trend toward higher mean AUC0-6 (P = 0.08) and Cmax (P = 0.08) values for Group III compared with Group I patients. Tc,max values were not influenced by prolonged cyclosporin treatment. The ratio of cyclosporin whole blood concentrations measured by the non-specific and specific RIA's (N/S ratio) increased with time without obvious differences between the three groups. These data suggest that cyclosporin absorption and its biotransformation in the liver are not impaired in patients with non-end stage PBC and that neither is affected by prolonged treatment. PMID- 1420739 TI - Omeprazole versus famotidine in the short-term treatment of duodenal ulcer disease. AB - The efficacy and safety of omeprazole, in 241 patients with active recurrent duodenal ulcer from 21 Italian centres, was studied in a multicentre double-blind randomized trial comparing 20 mg omeprazole o.m. or 40 mg famotidine nocte with endoscopic examination, symptom recording, laboratory screening and gastrin assay. In a per protocol analysis, the duodenal ulcer healing rates for omeprazole and famotidine, documented by endoscopy, were 62% (68/109) and 33% (39/117) after 2 weeks of treatment (P less than 0.001), 92% (96/104) and 80% (86/108) cumulative after 4 weeks (P less than 0.05), and 99% (102/103) and 92% (96/104) after 6 weeks (P less than 0.05), respectively. The results of this trial demonstrate that 20 mg omeprazole o.m. is superior to 40 mg famotidine nocte in duodenal ulcer healing. PMID- 1420740 TI - Influence of the timing of administration of 300 mg ranitidine on 24-hour gastric pH in patients acute duodenal ulcer. AB - The 24-hour intragastric pH of 12 patients with an acute duodenal ulcer was recorded with the aim of comparing the effects of two different times of administration of 300 mg ranitidine: post evening meal, or bedtime. This double blind crossover trial involved 3 centres. Twenty-four-hour gastric pH was measured under standard conditions (meals, time schedule) at the middle of each 14-day treatment period. The analysis was performed on the percentage of times spent at pH levels below 1.5, 2, 3 and 4 for different periods and for the total 24 hours. During the whole day and night combined, as well as during the afternoon (12.00 hours-19.00 hours), there was no difference between the 2 regimens regardless of the pH profile studied. During the morning (07.30 hours 12.00 hours), the time spent below pH 1.5 and 2 was less when the drug was taken at bedtime (P less than 0.05). In contrast, during the whole night (19.00 hours 07.30 hours) the percentage of time spent below pH 1.5, 2 and 3 was significantly less when the drug was taken at post evening meal (P less than 0.05). These results show that in patients with acute duodenal ulcer, 300 mg ranitidine administered at the end of the evening meal provides better control of nocturnal acidity than administration at bedtime and hence is suggested for optimization of therapeutic efficacy. PMID- 1420741 TI - Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin. AB - Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated. PMID- 1420742 TI - Short report: cefprozil for the eradication of Helicobacter pylori infection. AB - Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0 to 15%. We evaluated cefprozil (250 mg q.d.s. for 14 days) in 12 H. pylori-infected subjects. The 13C-urea breath test was used to evaluate effectiveness of therapy. Eradication was defined as a negative urea breath test 4 to 6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 4 of 12 (33%) by a negative urea breath test two days after start of treatment. H. pylori infection was not eradicated in any subject (0%). Adverse events were intermittent and mild. Cefprozil does not appear to offer promise as monotherapy for the eradication of H. pylori. PMID- 1420743 TI - Short report: comparison of the effects of sublingual nifedipine and isosorbide dinitrate on oesophageal emptying in patients with Chagasic achalasia. AB - The effects of sublingual nifedipine and isosorbide dinitrate on oesophageal emptying were compared in 11 patients with Chagasic achalasia. The oesophageal emptying of a radiolabelled test meal was assessed three times in each patient by a scintigraphic technique. No treatment preceded one of the studies (basal study). Nifedipine (20 mg) by the sublingual route 30 min before the meal, preceded one study. Isosorbide dinitrate, 5 mg by the sublingual route 5 min before the meal, preceded the third study. The order of the studies was allocated randomly for each patient. Oesophageal retention at the completion of the meal was significantly less (P less than 0.01) after isosorbide dinitrate (median: 54%, range: 5-87%) than after sublingual nifedipine (median: 78%, range: 7-99%) or after the control study (median: 83%, range: 5-100%). This difference persisted up to 20 min after the meal. Values measured in the control study and after sublingual nifedipine were not different (P greater than 0.10). These results show that isosorbide dinitrate, but not sublingual nifedipine, enhances oesophageal emptying in Chagasic achalasia. PMID- 1420744 TI - Short report: comparison of two orally administered bowel preparations for colonoscopy--polyethylene glycol and sodium picosulphate. AB - Fifty-nine consecutive patients admitted for colonoscopy were randomized to receive polyethylene glycol or sodium picosulphate. Patients expressed their opinion in a questionnaire and the endoscopists, blinded to the preparation, assessed the cleanliness of different segments of the colon. There was no statistically significant difference in the taste-acceptability of the preparations, frequency of nausea, abdominal pain, peri-anal soreness or sleep disturbance between the two groups. Polyethylene glycol caused vomiting in 13% of patients while this was absent in those who received sodium picosulphate (P less than 0.05). The average number of stools passed was 12.4 in the polyethylene glycol and 8.6 in the sodium picosulphate groups; mean difference 3.8 (95% C.I. 0.7-6.9) with P less than 0.02. The overall cleanliness of the colon was better in the polyethylene glycol group (P = 0.002) as judged by the blinded colonoscopist. There was less delay (P = 0.06) and more completed colonoscopies (P = 0.01) in this group. Polyethylene glycol was a better preparation in all segments of the colon except the rectum. We conclude that polyethylene glycol is the choice of the colonoscopist and should be given to all patients; sodium picosulphate would be a good alternative if patients are intolerant. If a limited colonoscopy or flexible sigmoidoscopy is intended, sodium picosulphate may be preferred because of its acceptable efficacy and slightly advantageous side effect profile. PMID- 1420745 TI - Review article: the pathophysiology and pharmacological treatment of portal hypertension. AB - The pathogenesis of portal hypertension remains poorly understood. Similarly, pharmacological manipulation for the prevention and treatment of variceal haemorrhage has not fulfilled the promise of the 1980s. This article reviews current concepts in the pathophysiology of portal hypertension and considers pharmacotherapy for the treatment of variceal bleeding. PMID- 1420746 TI - Review article: the treatment of alcoholic liver disease. AB - Over the past 20 years we have moved from a situation in which we had no therapy for alcoholic liver disease, through a period when any therapy we had was purely empirical, to an era where we have specific therapies for different aspects of this disease based upon sound pathogenic principles. In this short review, an attempt has been made to summarize these advances in the understanding of the pathogenesis of alcoholic liver disease. In particular, they explain why patients with severe acute alcoholic hepatitis continue to deteriorate in hospital despite withdrawal from alcohol, why they respond to corticosteroids, why only a small percentage of patients develop cirrhosis, and why propylthiouracil may offer protection. PMID- 1420747 TI - Comparison between a standard pancreatic supplement and a high enzyme preparation in cystic fibrosis. AB - This study compared the relative effectiveness of a standard pancreatic enzyme supplement ('Creon', Duphar) and a new preparation ('Pancrease HL', Cilag) containing about 3 times the lipase and more than 5 times the protease activity. Capsule dosage was adjusted to a ratio of approximately 3:1. Fat balances showed that absorption of fat did not change significantly on conversion to the new high lipase product, and the coefficient of absorption of total energy was similarly maintained. The coefficient of protein absorption was significantly enhanced with the high enzyme preparation (P less than 0.01), which may explain the reported subjective improvement in stool odour. No adverse effects were recorded. Patient acceptability of the new compound was high; the great reduction in the number of capsules required at each meal was cited by all patients as the reason for their preference. PMID- 1420748 TI - Omeprazole in the long-term treatment of severe gastro-oesophageal reflux disease in patients with systemic sclerosis. AB - Twenty-five patients with systemic sclerosis and severe gastro-oesophageal reflux disease were treated with 20-80 mg omeprazole daily for up to 5 years. Efficacy of treatment was assessed by symptom score, by endoscopic and histopathological surveillance of the oesophageal and gastric mucosa, and by laboratory screening including serum gastrin concentration. Statistically significant relief of symptoms and healing of oesophagitis confirmed the efficacy of this treatment. However, complete healing of oesophagitis was not achieved in half of the patients due to residual gastro-oesophageal acid reflux. Repeated adjustments of the maintenance dose of omeprazole may be needed for this group of patients. From the safety point-of-view, nothing was observed to discourage the long-term use of omeprazole in this group of patients. PMID- 1420749 TI - A comparison of gastro-oesophageal reflux in volunteers assessed by ambulatory pH and gamma monitoring after treatment with either Liquid Gaviscon or Algicon Suspension. AB - This study was designed to compare the effectiveness of single doses of either Liquid Gaviscon or Algicon Suspension in the suppression of food and acid reflux into the oesophagus after a test meal in volunteers. After the pH electrode and gamma detector were positioned 5 cm above the cardia, the volunteers received a refluxogenic radiolabelled meal. The subjects then remained untreated, or thirty minutes later they were given a dose of unlabelled Algicon Suspension, or Liquid Gaviscon and a recording was made for a minimum of 3 hours. Allocation to the treatment group was randomized with the cross-overs performed 1 week apart. Liquid Gaviscon suppressed gastro-oesophageal reflux of both food and acid whereas only an insignificant reduction in reflux was seen after Algicon Suspension. The oesophageal pH remained below 4 for 3.21 +/- 0.92% (S.E.M.) of the recording period in the control study, 0.88 +/- 0.33 after Gaviscon and 2.91 +/- 0.68 after Algicon. The reflux of food was reduced from 17,070 x 10(3) +/- 4713 x 10(3) counts in the control study to 224 x 10(3) +/- 93 x 10(3) counts after the Gaviscon and 16,080 x 10(3) +/- 7131 x 10(3) counts after Algicon. The suppression of reflux by Liquid Gaviscon was significantly better than that produced by Algicon Suspension. PMID- 1420750 TI - Oral or intravenous erythromycin has no effect on human distal colonic motility. AB - Erythromycin is a prokinetic agent for the lower oesophageal sphincter, the stomach, the gallbladder and the small bowel, acting directly on motilin receptors. Its effect on pressure activity of the human colon has not been investigated. Eight healthy volunteers were studied on 2 occasions and given intravenous or oral erythromycin, or placebo in a single-blind, randomized crossover study. Sigmoid pressure activity was measured using a 4-lumen water perfused system placed sigmoidoscopically at 50, 45, 30 and 15 cm from the anal verge. The pressures were analysed for activity index (mmHg.min) for the 35 cm colonic study segment using dedicated software. No significant difference was found in the activity index following oral erythromycin (500 mg) or placebo, or following intravenous erythromycin 1.8 mg/kg or placebo. A further 8 subjects were studied in a single-blind crossover study to determine the effect of oral erythromycin (500 mg) b.d. on colonic transit, measured with radio-opaque markers and a single abdominal X-ray. Mean or segmental colonic transit times were not statistically significantly different (Student's paired t-test) in the subjects on placebo or erythromycin. This lack of effect of erythromycin on the distal large intestine may indicate the absence of receptors for motilin in that part of the gut. PMID- 1420751 TI - Ranitidine for erosive oesophagitis: a double-blind, placebo-controlled study. Glaxo Erosive Esophagitis Study Group. AB - A multicentre, randomized, double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of ranitidine 150 mg and 300 mg in 342 patients with erosive oesophagitis. Treatment was given four times daily, and continued for 12 weeks or until healing (that is, normal or only erythematous mucosa). Erosive oesophagitis healing rates, as determined by endoscopy, were significantly greater in ranitidine-treated patients by 4 weeks compared with those of placebo-treated patients. By 12 weeks, erosive oesophagitis healing rates were 83 and 81% for ranitidine-treated patients (150 and 300 mg, respectively) and 58% for placebo-treated patients (P less than or equal to 0.001, ranitidine vs. placebo). Symptomatic relief was achieved within 24 hours after starting either dosage of ranitidine. Heartburn frequency (P less than 0.001) and severity (P less than 0.001), as well as antacid consumed per week (P less than 0.001), were reduced in both ranitidine groups in comparison with placebo. Healing rates and symptom relief were similar in the two ranitidine groups. Both dosages of ranitidine were well tolerated. Ranitidine (150 mg) given four times daily appears to be as effective as 300 mg ranitidine given four times daily in patients with moderate to severe oesophageal erosions. PMID- 1420752 TI - The effect of combined therapy with ranitidine and pirenzepine in the treatment of reflux oesophagitis. AB - The combination of a histamine H2-receptor antagonist and a muscarinic receptor antagonist has been reported to result in greater suppression of intragastric acidity than either agent alone. The present randomized, double-blind, multicentre trial compared the effects of the oral combination of 150 mg ranitidine b.d. plus 50 mg pirenzepine b.d. with 150 mg ranitidine b.d. plus placebo pirenzepine b.d. in the treatment of patients with reflux oesophagitis. All 157 patients had symptoms of gastro-oesophageal reflux with endoscopically confirmed oesophageal erosions (Savary and Miller grades I-III). After four weeks of treatment, healing rates were 32/75 (43%) in the combined treatment group and 34/76 (45%) in the group receiving ranitidine alone. After eight weeks, the cumulative healing rates had increased to 48/72 (67%) and 51/75 (68%), respectively. More patients receiving ranitidine plus pirenzepine had complete relief of day- and night-time heartburn after four weeks compared with those receiving ranitidine alone (day: 59% vs. 38%, P = 0.02; night: 69% vs. 52%, P = 0.04). After eight weeks, symptom relief was comparable in both groups. Clinical adverse effects were reported by nine patients receiving ranitidine and by 19 patients receiving the combination. It is concluded that combining ranitidine with pirenzepine does not aid the healing of reflux oesophagitis but does improve symptom relief at four weeks. PMID- 1420753 TI - Nine years of maintenance treatment with ranitidine for patients with duodenal ulcer disease. AB - Four hundred and sixty-four patients with duodenal ulcer disease received continuous maintenance treatment with ranitidine for up to 9 years. Treatment failure was defined as either the first symptomatic recurrence of ulcer or the first ulcer recurrence accompanied by haemorrhage. Life tables were constructed using the Kaplan-Meier product-limit method; comparisons of survival curves were performed using the log-rank test; and multivariate analysis was carried out using the Cox proportional hazards model. Results. The proportion of patients remaining free from symptomatic recurrence of ulcer during maintenance treatment with either 150 mg/day or 300 mg/day ranitidine was: 95% at 1 year; 88% at 3 years; 86% at 5 years; and 81% at 7 and 9 years (95% C.I. 76-86%). Young age and the absence of exposure to non-steroidal anti-inflammatory drugs (NSAIDs) at the time of diagnosis of ulcer were shown to increase the likelihood of developing ulcer recurrence. The rate of ulcer recurrence after 9 years of maintenance treatment (17%) was significantly less than that after 5 years without active anti-ulcer therapy (80%), P = 0.0001. The proportion of patients who remained free from ulcer haemorrhage during maintenance treatment was: 99.1% at 1 year and 98.1% at 5 and 9 years (95% C.I. 96.7-99.6%). The risk of haemorrhage was significantly greater in patients who were not receiving active treatment (12.4% at 5 years) than in patients receiving maintenance treatment (less than 2% at 9 years), P = 0.0001 (log-rank test). Patients who had originally presented with haemorrhage had an increased risk of further ulcer bleeding compared with patients who presented with pain (P = 0.0013). A significantly greater proportion of patients with NSAID-associated duodenal ulcers remained free from ulcer recurrence during maintenance treatment compared with patients suffering from 'idiopathic' ulcers (P = 0.0238), although there was no difference between the two groups in respect of haemorrhage during maintenance treatment. Conclusions. (a) Continuous maintenance treatment with ranitidine for up to nine years successfully prevents ulcer recurrence in more than 80% of patients with duodenal ulcer disease. (b) Young age increases the risk of ulcer recurrence during maintenance treatment with ranitidine. Ulcers associated with NSAID-intake at the time of diagnosis have a lesser risk of recurrence during maintenance treatment. (c) The risk of haemorrhage in patients with ulcer disease receiving maintenance treatment with ranitidine for nine years was less than 2% compared with greater than 12% in untreated patients observed for 5 years.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1420754 TI - Short report: comparison of two doses of balsalazide in maintaining ulcerative colitis in remission over 12 months. AB - In a four-centre prospective double-blind trial, 108 patients with ulcerative colitis in remission were randomized to receive balsalazide in doses of 3 g or 6 g/day for 12 months. The patients were assessed at 3-monthly intervals clinically, sigmoidoscopically and with routine haematology and biochemistry. Remission rates of 77% (3 g/day) and 68% (6 g/day) at 12 months were not significantly different. Intolerance reactions leading to withdrawal from the study occurred in only 9 patients (8%), all occurring in the first 7 weeks of the study. Balsalazide is therefore both highly effective in maintaining remission in ulcerative colitis and well tolerated in both conventional and high dosage (the latter equivalent to 5.5 g/day of sulphasalazine). In this study no distinct advantage in maintenance of remission has been found for the higher dose of balsalazide. PMID- 1420755 TI - Gastrointestinal side-effects of NSAIDS. PMID- 1420756 TI - [Perspectives of immunosuppressive treatment for the prevention of diabetes mellitus type I]. PMID- 1420757 TI - [Infectious endocarditis in parenteral drug addicts: study of 57 cases]. AB - We present 57 cases of infectious endocarditis (IE) in 51 parenterally drug addicts (PDA) admitted at the Internal Medicine Service of the Hospital Clinico of Valencia between January ist, 1988 and January 15th, 1992. The disease affected young patients, 84% of them being HIV-1+ and 86% presenting CD4+ lymphocytes lower than 200 cells/mm3. Fever was the most constant symptom, with radiological disorders and presence of vegetations by echocardiogram in 65% and 53% of episodes, respectively, and affectation of the tricuspid valve in 59% of patients. The diagnosis of endocarditis was definitive in 51% of cases, possible in 15% and probable in 22%, being cardiac failure the most severe complication, present in 23% of episodes. The detection of significant valve regurgitation in patients with IE and without developing cardiac failure is not predictive of future complications, nor its absence identifies patients with a favourable prognosis. Staphylococcus aureus was the most frequently isolated germ (48%), being methicillin-resistant in 15% of cases and with a slower response to the treatment with vancomycin than the methicillin-sensitive. Five patients died, all of them with CD4+ lower than 50 cells/mm3, which may have a predictive value in the follow-up of these patients. PMID- 1420758 TI - [Epidemiology of obesity among the adult population of Catalonia]. AB - Several epidemiological studies have shown that obesity is related to the mortality from cardiovascular disease. In this study, the epidemiology of obesity and the correlation between body mass index and other cardiovascular risk factors was studied in a representative sample of the adult population of Catalonia. It was obtained a random sample (n = 704) of the adult population of Catalonia aged 15 or more years. Height and weight were measured and body mass index (BMI) was calculated (height in Kg/weight2 in m2). Obesity was defined as a BMI greater than 30, and overweight as a BMI from 25 to 30. In the first 314 participants, it was determined the concentration of total cholesterol, cholesterol-HDL and triglyceride, and it was measured the blood pressure. The correlation between BMI and other cardiovascular risk factors was analysed. The study was carried out in 1989. The mean of BMI increased with age in both sexes. BMI was significantly higher in men (26 kg/m2) than women (25 kg/m2). The prevalence of obesity was of 12% in both men and women, and the prevalence of overweight was of 48.5% in men and 38% in women. The prevalence of arterial hypertension, hypercholesterolemia and diabetes was greater individuals with obesity, with differences statistically significant for hypertension (odds ratio of 3.26). The multiple logistic regression analysis showed that the association between obesity and hypertension was not statistically significant (OR adj. = 2.09), when the effect of the other risk factors, the age and sex were controlled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420759 TI - [Comparative study of von Willebrand factor in patients with temporal arteritis]. AB - Giant cell arteritis, temporal arteritis (TA), is a vasculitis which affects large and medium-sized vessels. The von Willebrand factor (vWF) is synthesized by endothelial cells and megakaryocytes. Increased amounts of vWF are released into plasma in response to an endothelial damage. vWF levels were studied by Electro Immunodiffusion in 16 patients with TA (8 of them with a positive biopsy) and their values were compared with 5 patients with Polymyalgia Rheumatica (PMR) and 32 controls. We found higher amount of vWF in global TA, biopsy-positive TA, biopsy-negative TA, and PMR than in controls. There were no relationship between vWF amounts in plasma and clinical findings nor the laboratory parameters. We feel that although in our study vWF might be of some help as an alternative to the biopsy in those patients with high suspicion of TA, the results of other authors raise doubt about the usefulness of the determination of vWF in TA. PMID- 1420760 TI - [Dual photon absorptiometry in algodystrophy]. AB - Biphotonic absorptiometry has begun to demonstrate its usefulness in the field of osteoporosis. In algodystrophy, the radiology and the degree of isotopic fixation suggest a bone disorder, although both techniques are unable to objectively quantify it. Biphotonic absorption is an scanning technique which allows the quantification of bone demineralization in the segment affected by algodystrophy and its evolutive follow-up. PMID- 1420761 TI - [Hepatic cirrhosis and alpha 1-antitrypsin deficit: a family study]. AB - Hepatic cirrhosis secondary to deficit of alpha-1 antitrypsin is an entity rarely observed among the adult population. We describe the clinical and histological characteristics of a patient with PiZZ phenotype, affected by an hepatic cirrhosis of this etiology, as well as the analytical and phenotypical study of his close relatives, all of which presented a type-Z mutation. PMID- 1420762 TI - [Bardet-Biedl syndrome: subclinical renal disorders in 2 siblings]. AB - Two siblings with Bardet-Biedl's syndrome are studied, in whom renal structural and functional disorders were observed, with reduction in the ability to concentrate urine in both cases and decrease of creatinine clearance in the second case. The study of the hypophyseal function was normal. PMID- 1420763 TI - [Fahr's disease and hypocalcemic syndromes. Presentation of a clinical case]. AB - A clinical case of a man with calcification of basal ganglions (CBG) is presented. The first manifestations of this syndrome were loss of consciousness and convulsions. The potential causes of his hypocalcemia, Fahr's syndrome, myocardiopathy of hypoparathyroidism and hypocalcemia are reviewed and a study oriented to autoimmune polyendocrinopathy is performed. PMID- 1420764 TI - [Hepatic hemangiomas and rheumatoid arthritis in patients treated with azathioprine]. AB - Two clinical cases of patients with rheumatoid arthritis (RA) and poor response to conventional treatment are described. Patients received immunosuppressor treatment with azathioprine (AZA) and developed hepatic hemangiomas without detectable hepatic pathology previous to the treatment with AZA. The hepatic iatrogenesis of AZA is discussed, as well as the etiopathogenic hypothesis regarding hepatic hemangioma. PMID- 1420765 TI - [Clinical syndromes in HIV infection (part 2)]. AB - The spectrum of clinical manifestations associated to HIV infection is very broad. In addition to processes that may be attributed to the virus itself, multiple opportunistic infections can develop while the immunodeficiency develops. Any organ or system of the organism may be affected by these processes. The main clinical syndromes in AIDS and the differential diagnosis of their potential etiologies are reviewed. PMID- 1420766 TI - [Clinical and diagnostic characteristics of Aeromonas strains]. AB - We studied the taxonomic, clinic, microbiological diagnostic and therapeutic characteristics of Aeromonas strains. Eleven geno-species have been isolated in human. They can be enterotoxigenic or enteroinvasive. These bacteria can be easily confused with other Gram negative bacilli (the Aeromonas are oxidase positive). They produce diarrhea but can only colonizer. In others localizations they are always diagnostic. Their detection in stools can be realized with the blood agar plus ampicillin or cefsulodin-novobiocin-irgasan agar. The treatment of extraintestinal infection is similar to the Gram negative infections. The Aeromonas are resistant to erythromycin, streptomycin and first generation cephalosporin. The beta-lactamic antimicrobials aren't the election treatment because the are positive beta lactamase. The diarrhea in children and immunocompromised or chronic patients will be treated with cotrimoxazole or fluorquinole. PMID- 1420767 TI - [Screening in primary health care. Presentation of a case of familial hemochromatosis]. PMID- 1420768 TI - [Late hydrothorax due to parenteral nutrition]. PMID- 1420769 TI - [Cyclosporine-verapamil interaction]. PMID- 1420770 TI - [Cutaneous metastasis of pulmonary epidermoid carcinoma]. PMID- 1420771 TI - [Physical exercise in family and community medicine]. PMID- 1420772 TI - [The introduction of a new specialty program]. PMID- 1420773 TI - [Maternal attitude to breast feeding and difficulties in the immediate puerperium]. AB - OBJECTIVE: To investigate the attitudes of women who have just given birth towards breast feeding according to their social class and level of education, as well as the problems arising during their stay in hospital, and the possible repercussions the latter might have. DESIGN: Transversal descriptive study, based on random sampling. SITE. The Maternity Unit of the "Marques de Valdecilla" University Hospital, Santander. PARTICIPANTS: 100 mothers of newborn babies chosen at random amongst those who had given birth vaginally to normal babies after a nine months pregnancy. RESULTS: The results from the questionnaire show that: 35% derived their information on breast feeding from magazines, 25% from the psychoprophylactic obstetrician (PPO), 28% had no information. 60% of the sample took the decision to breast-feed before pregnancy, 21% during the pregnancy, and 6% after the birth. 78% of the children were fully documented at the hospital on: first time at the breast, frequency of feeds, glucose solution supplement. 60% of the mothers evidenced problems with their breasts. On leaving hospital, 83% were breast feeding. CONCLUSIONS: To continue promoting breast feeding and helping mothers not to have so many problems at the beginning, we should use primary health attention, PPO courses and prenatal education as platforms for action, emphasising the importance of preventive care of the breast and breast-feeding technique. Hospitals should incorporate the international recommendations on initial lactation, with subsequent reinforcement during home visits and health centre appointments. PMID- 1420774 TI - [Major and minor changes in the electrocardiogram of the hypertensive patient]. AB - OBJECTIVE: To determine the prevalence and characteristics of electrocardiograph deviation in such hypertensive patients. DESIGN: Retrospective descriptive study of a representative sample of patients with high blood pressure. SITE. Primary attention centre. PATIENTS: The sample consists of 352 patients, systematically random selected from a pool of 1780 patients suffering from hypertension, aged over 14 years, attending the centre (119 males (34%) and 233 females (66%). Average age 59.4 +/- 13.5 years). MAIN MEASUREMENTS AND RESULTS: The first ECG reading after diagnosis of hypertension was analysed and codified according to the pooling project criteria. 38.9% present electrocardiograph deviations, the most frequent being minor wave 1 (12%), significant breaking up of the ST (9%) and left ventricular hypertrophy (5.1%), the latter more frequent in women (p = 0.03). Age, systolic arterial blood pressure and the time the condition had been in existence, certain associated chronic diseases, and use of pharmaceutical drugs acting cardiovascularly, are positively related to the deviation in ECG (p < 0.05). CONCLUSIONS: The value of ECG in the treatment of high blood pressure sufferers is indicated. PMID- 1420776 TI - [The appropriateness of emergency referrals sent from primary care to a general hospital]. AB - OBJECTIVE: Study of the degree of completeness of slips sent to forward patients from primary medical care to emergency units of the corresponding general hospital. DESIGN: This is a statistical descriptive and inferential study. SITE. The study was carried out in the general hospital allocated to Zaragoza Health Area III. PATIENTS: Included in the study are all patients sent by primary medical care for evaluation by the urgency unit in the internal medicine section. MAIN MEASUREMENTS AND RESULTS: 415 urgent treatment slips were analysed, evaluating the completion rate and the degree of correctness in relation to their source as either rural or urban. With regards the degree of completion (clinical history, antecedents, examination) and correct functioning at the visit to family doctor stage, there are highly significant differences between those sent from all other such centres (p less than 0.01). Only in the case of 8 slips were physical examinations completed for the presenting ailment: 7 came from urban health centres and 1 from rural health centres. Diagnostic impressions and observations were absent from 62.2% of the slips. CONCLUSIONS: While overall there is no difference between those sent from rural and urban centres, there were differences when those sent from urban health centres were compared with those sent by all other health centres. PMID- 1420775 TI - [Mental disorders and the utilization of the general medicine consultation]. AB - OBJECTIVE: To study the quantitative relationship that exists between mental problems and use of the general medical practitioner, and the association between such problems, increased use of the medical services, and morbidity and socio demographic variables. DESIGN: Observational cross-section study. SITE. A primary care team's general medical consultations. PATIENTS: Patients aged over 15, attending the consultations. A sample of 310 patients was selected using systematic sampling. INTERVENTIONS: The Mental Health GHQ, 28 items questionnaire was administered to the patients, to detect the existence of significant mental health disorders. MEASUREMENT AND MAIN RESULTS: Amongst older patients there is a greater incidence of mental illness, statistically significant at p less than 0.01. Also significant at p < 0.01 were the greater number of visits to the doctor amongst patients previously diagnosed as having mental disorders, amongst the elderly, those patients included in health programmes and those who showed greater take-up of supplementary explorations and interim consultations. CONCLUSIONS: The results demonstrate an association between mental illness and greater number of visits to the general practitioner, leading to the hypothesis that a considerable number of such visits could be attributed to mental illness. There is no doubt that it is important to integrate the mental health services into primary care practice. PMID- 1420777 TI - [The approach to the etiological diagnosis of hyperlipemias in primary care]. AB - OBJECTIVE: To perform etiological diagnosis of hyperlipidemia (HL) brought to light in family medical (general practice) consultations. DESIGN: Retrospective descriptive study. SITE. A basic health zone (ZBS). PATIENTS: 231 patients diagnosed as having HL by their doctors. MAIN MEASUREMENTS AND RESULTS: Lipidic levels (average figures): total cholesterol (CT): 280; C-LDL: 201; C-HDL: 49 and triglycerides (TGL): 198. Distribution by phenotypes: IIa: 178 patients, IIb: 42, IV:5, with 6 doubtful cases. Distribution according to etiological diagnosis: 79% primary HL (83% polygenic and 17% family) 15% secondary HL, with 6% having both types in association. CONCLUSIONS: Diagnosis of HL in the visits to the family doctor reveals probability-predictable patterns based, above all, on the the overall assessment made by the doctor of his/her patient. The survey and the family study are very limited in our circles. The predominating type of HL is primary polygenic where prescribing of special diets will be sufficient in most cases. PMID- 1420778 TI - [Hyperuricemia and gout]. PMID- 1420779 TI - [The classification, diagnosis and control of asthma]. PMID- 1420780 TI - [The family and advanced cancer]. PMID- 1420781 TI - [A method of identifying problems and of detecting diagnostic deficiencies by using the primary care center information system]. PMID- 1420782 TI - [The knowledge and consumption of drugs by 7th-grade schoolchildren of]. PMID- 1420783 TI - [The prioritization of health problems by the community: a very educational experience]. PMID- 1420784 TI - [Acute hepatitis: an adverse reaction to fenofibrate treatment]. PMID- 1420785 TI - [A case of taeniasis in primary care]. PMID- 1420786 TI - [A descriptive study of hypercholesterolemia in a population assigned to a family physician]. PMID- 1420787 TI - [Family medicine in the new Europe]. PMID- 1420788 TI - [Primary care reform and consumer satisfaction]. PMID- 1420789 TI - [Follow-up of the quality of drug prescriptions: the Primary Care Center of Badia City (1986-1990)]. AB - OBJECTIVE: To determine the variation in the quality of prescription of medicines in Primary Attention Centre in two different periods, 1986 and 1990. DESIGN: Longitudinal, retrospective study with direct intervention. SITE. Primary Attention Centre, Ciudad Badia. PARTICIPANTS: 1986: 9 general practitioners in medicine (GPs) and 7 pediatricians. 1990: 9 Gps, 7 pediatricians, and 7 residential doctors (MFC based) who were not included in the earlier evaluation. INTERVENTION: Once the 1986 prescriptions had been analysed qualitatively, the results were made available to and discussed with the doctors who made out the prescriptions (passive feedback). As ongoing intervention the periodic clinical sessions should be considered. MAIN MEASUREMENTS AND RESULTS: Increase in the substances included in Index/Guide: MG 6.5% and P 13% (p < 0.00001). Increase in the number of substances with an active principle and in the combinations accepted: MG 2.3% and P 9% (p < 0.00001). Increase in the percentage of specialties with high V1: MG 1% (p = 0.12) and P 10% (p < 0.00001). CONCLUSIONS: There has been an increase in the quality of medical prescriptions according to the indicators analysed. There are other external factors that effect prescriptions that are difficult to measure. This type of study allows one to pinpoint the excessive or wrong use of intrinsically not very valuable sub-groups of therapeutic substances, and will serve as a base for indication-prescription studies. PMID- 1420790 TI - [Effect of post-natal visit on the involvement in the activities of the mother child program]. AB - OBJECTIVES: Ascertain what effect post-natal visits have on recruiting involvement in the mother and child programme of activities. Identify the profile of mothers and children with little involvement in these activities. Ascertain how suitable the register is. DESIGN: Study of cohorts of previous years. The term exposed cohort refers to mothers who received the postnatal visit in 1989, and non-exposed cohort to those who did not receive one. SITE. Health Centres in Almanjayar and Cartuja. Primary Attention. Evaluation of the services offered. PATIENTS OR OTHER PARTICIPANTS: The sample consisted of the 166 women whose pregnancy we monitored from the Centre, and who gave birth between January and December 1989. MAIN MEASUREMENTS AND RESULTS: The most indicative results show that the group that received the post-natal visit tended to attend the healthy child clinic, family planning and metabolism testing services, with greater frequency, and to breast feed longer. The differences are only significant (p = 0.004) in the case of family planning. CONCLUSIONS: We positively evaluate the post-natal visit because of its contribution to the early detection of the problems of mother and child, and to recruitment into Family Planning. And because the examining risk has meant that factors associated with reduced coverage by the services (ethnicity, educational level, mother's age) did not act as such in our study. PMID- 1420791 TI - [Effect of the physician's and the patient's sex on the clinical interview]. AB - OBJECTIVE: To analyse differences attributable to the sex of the doctor and of the patient in the activities and content of the clinic appointment in Primary Attention. DESIGN: Analysis of interaction, in terms of activities and content, in 157 clinic appointments. SITE. General medical consultations in four Primary Attention Public Health Centres. PATIENTS: Those who used the health services on the day of the study. INTERVENTION: Tape recording of the appointments. MAIN MEASUREMENTS AND RESULTS: The interviews were recorded. There were shown to be differences according to the sex of the doctor and of the patient in terms of the development and content of the interviews. The style of the woman doctor involved longer interviews with greater social content; in general sameness of sex (doctor and patient) led to greater mutual complementation in the interviews. CONCLUSIONS: It has been shown that there are differences in the activities and content of the clinic appointments in Primary Attention which depend on the sex of the patient and doctor. PMID- 1420793 TI - [Spontaneous hematoma of the rectal muscles as a cause of abdominal pain with palpable mass]. AB - OBJECTIVE: To carry out a review of hematoma in the abdominal wall: etiology, triggering factors, diagnosis and treatment. To consider differential diagnosis with other causes of acute abdominal pain with palpable mass. DESIGN: Based on two clinical observations. SITE. Iscar Health Centre, Valladolid. PATIENTS: Two patients who presented themselves at Casualty complaining of acute abdominal pain and with palpable abdominal mass (lump). MAIN MEASUREMENTS AND RESULTS: The anamnesis and physical exploration provided the tentative diagnosis, and they were sent to the Hospital centre in question. The analyses, X-rays and abdominal scans were not conclusive and an abdominal laparotomy was carried out which confirmed the diagnosis. CONCLUSIONS: Spontaneous haematoma in the abdominal wall is a cause of acute abdominal pain which is encountered most frequently in women receiving anticoagulant treatment or in situations that increase abdominal muscular tension (coughing, pregnancy, constipation, previous laparotomies and intraabdominal injections). Confirmation of initial diagnosis is obtained, normally, using sonic scanners, or abdominal TAC, but on occasions findings are not conclusive, and are submitted to abdominal laparotomy. The treatment is conservative except with hemodynamic complications. PMID- 1420792 TI - [Evaluation of the quality of prenatal care in primary care]. AB - OBJECTIVE: Determine the quality of prenatal assistance by means of an audit. DESIGN: This is a retrospective and longitudinal observational study. SITE. At the Primary Attention level, at the "La Chana" Health Centre, Granada. PATIENTS: 514 mothers-to-be. MAIN MEASUREMENTS AND RESULTS: The completion rate of the programme was studied via twelve indicators. Gynecological examination during the first visit (37.74%), serology of infections and toxoplasma (32%) and AgHBs (14.28%) were the indicators least carried out. Gestatory age (98.84%) probable date of the birth (98.45%) and arterial blood pressure (96.7%) were those most frequently carried out. CONCLUSIONS: Motivation exists in the Primary Attention team to record complete medical histories. Need to: unify therapeutic diagnostic criteria, increase coordination between the different levels of attention, and carry out audits more often, to evaluate the quality of attention given objectively. PMID- 1420794 TI - [Report on continuing care in 1990 at the Health Center I of Ciudad Real]. AB - OBJECTIVE: To determine what justification there is for Continuous Attention (CA). Secondly the ranking of processes, derivations and effect of the time of year. DESIGN: Descriptive longitudinal and retrospective study. Observational, non-controlled and without random distribution (all cases) and non-blind. SITE. Primary Attention (PA). PATIENTS: All people who attended the Health Centre (HC) from 3-5 pm, in 1990. INTERVENTION: None that would affect the results. MAIN MEASUREMENTS AND RESULTS: Most of those attending did so for IRA's, contusions, wounds, sprains and abdominalgias (table 1). 6.6% were derived, mainly digestive and traumatological processes (table 2). CONCLUSIONS: Compared with similar studies, the demand generated by our population is optimal both in numbers and in justification. Among the, subjectively-speaking non-justified visits the reasons were to avoid ordinary doctors appointments, to get second opinions, to obtain prescriptions, complementary analyses and hospitalisation, and obtain results more quickly, under the emergency service. A significant number of children are attended by general practitioners (GPs), and this induces private consultation. Derived cases are 6.6%, less than the standard 15%. One third of these cases are not hospitalised, especially in months when hospital demand is at its maximum. The lack of coordination between our service and the hospital casualty service is obvious, leading to amongst other things, the "rebound" effect on the user. Closeness between the two services means that an estimated 15% go directly to hospital, a fact which could diminish comparability between this and other studies, although in treating the whole series, the reliability of this study is improved. PMID- 1420796 TI - [Treatment of bronchial asthma]. PMID- 1420795 TI - [Preliminary study of smoking cessation at 6 months following medical counseling, pamphlet, and follow-up]. AB - OBJECTIVES: Preliminary study to evaluate the results of a programme to help smokers. DESIGN: Study involving direct intervention, with control group, and with random distribution in experiment group and control group. SITE. The study was carried out in the patients' visits of the five doctors at Primary Attention on the afternoon shift, "V Centennary" Health Centre, San Sebastian de los Reyes, Madrid. PATIENTS: 102 smokers aged from 21 to 67 years who attended the appointments for any reason were selected. INTERVENTION: The participants in the experiment group (n = 48) were given a structured talk which lasted ten minutes and were supplied with a "Guide to Giving up Smoking". The control group (n = 50) were advised to give up the habit. We checked consumption by telephoning subjects, after 30 days, 90 and 180. MAIN MEASUREMENTS AND RESULTS: After 30 days 12 individuals (25%) from the experiment group had given up smoking, and 4 (8%) from the control group. After 90 days 12 subjects from the former group did not smoke (25%) compared with 3 (6%) from the latter. After 6 months 10 out of the former group did not smoke (20.8%) and 5 individuals from the latter (10%) (not significant). CONCLUSIONS: Subjects were positively receptive to the medical advice received from their doctors. The level of non-smoking observed after 6 months is clinically significant, although the difference between the two groups is not statistically significant, possibly as a result of the small size of the sample. PMID- 1420797 TI - [Treatment of sexually transmitted diseases]. PMID- 1420798 TI - [Usefulness of spirometry in asymptomatic young smokers]. PMID- 1420799 TI - [Role of nursing in chronic prescription]. PMID- 1420800 TI - [Chronic prescription]. PMID- 1420801 TI - Thyroid autoimmunity. PMID- 1420802 TI - Preferential use of T-cell receptor V genes in human autoimmune thyroid disease. AB - We review here our analyses of hTcR V gene activity within the thyroid glands of patients with autoimmune thyroid disease. Our data, based on thyroid aspiration specimens, indicate that early in the onset of Graves' disease there is a marked restriction in both hTcR V alpha and V beta gene families utilized by intrathyroidal T-cells. Later, however, and as seen in surgical thyroid specimens from patients with long term disease, there appears to be a loss of V beta restriction for unclear reasons. In contrast, patients with Hashimoto's thyroiditis are usually diagnosed later in the natural history of the disease and appear to show much less hTcR V gene family restriction. The mechanisms driving the use of few and many hTcR V genes within the thyroid gland are likely to be complex and may reveal important insights into disease pathogenesis. PMID- 1420803 TI - Cytokines and immune regulation in thyroid autoimmunity. AB - We studied the role of cytokines and immune regulation in thyroid tissue from patients with Graves' disease. Immunohistochemistry showed that the thyroid glands are characterized by an aberrant expression of HLA class II antigens on thyrocytes, generation of new blood vessels and infiltration of mononuclear cells. We demonstrated that CD4+ memory cells were more frequent in thyroid glands from Graves' patients than were CD4+ naive cells. The intrathyroidal T cells demonstrated an enhanced expression of the adhesion molecules LFA-1, CD2, VLA-4 and VLA-5, and vascular endothelial cells of capillaries and thyrocytes in thyroid glands reacted with anti-ICAM-1 monoclonal antibody. The adhesion molecules and HLA antigens on both vascular endothelial cells and thyrocytes were regulated by inflammatory cytokines. These results suggest that circulating lymphocytes migrate into thyroid tissues and that memory T cells are retained in the thyroid tissues by cellular interactions with thyrocytes or with extracellular matrix. PMID- 1420804 TI - A perspective on human autoimmune thyroid disease: is there an abnormality of the target cell which predisposes to the disorder? AB - It has been suggested recently that autoimmunity could be regarded as a physiological response of the normal immune system to autoantigens caught up in an inflammatory response to viral or bacterial antigen expressed in the target tissue. Other theories to explain autoimmunity include molecular mimicry whereby a viral or microbial hapten similar to an autoantigen initiates the production of autoantibodies that cross react with an autoantigen, with a subsequent immune response reacting with autologous cell structures which are homologous with the particular microorganism. There has also been a suggestion that there may be a genetic abnormality of the target cell which is necessary for the initiation of autoimmune thyroid disease. The present review examines these proposals and provides evidence against an antigen-driven origin for autoimmune thyroid disease (AITD). Currently, there is no valid evidence for viral involvement, and likewise the evidence for molecular mimicry as an initiating factor does not hold up to scrutiny. While a genetic abnormality of the thyrocyte may be important in certain animal models of AITD, in the human there is no evidence for such an abnormality. Evidence that AITD is derived from a disturbance of immunoregulatory mechanisms has been documented elsewhere and would appear to be the most appropriate explanation for these disorders. The immunoregulatory disturbance itself may be related to an abnormality of the mechanism of specific antigen (i.e. normal autoantigen) presentation to appropriately induce T lymphocytes and that theory will require further illumination. PMID- 1420805 TI - Intrathyroidal activated (Ia+) T-lymphocyte CD+ subsets and B cells in Graves' hyperthyroidism respond rapidly to propylthiouracil therapy: demonstration using fine needle aspirates and two-colour laser flow cytometry. AB - Using a rapid (whole blood lysis) single laser microfluorocytometric technique that permitted the simultaneous analysis of two monoclonal antibody surface markers tagged with different fluorescent dyes, the intrathyroidal (IT) and peripheral blood (PB) activated [Ia+ = DR+] T-lymphocyte CD3+ subsets and [F(ab')2+] B cells were studied in hyperthyroid patients with Graves' disease (GD) before and after 1-4 months of propylthiouracil (PTU) therapy. IT lymphocytes were obtained by serial fine needle aspiration. In untreated patients a marked quantitative (approximately < 10 fold) increase in activated (Ia+ CD3+) T-lymphocytes as well as CD4+ and CD8+ subsets, for IT compared to PB sites, was found. The percentages of Ia+ CD4+ and Ia+ CD8+ within Ia+ CD3+ were not significantly different between the two sources of T cells. F(ab')2+. B cells were significantly increased (approximately 2-3 fold) in IT compared to PB. In hyperthyroid GD patients, PTU therapy induced rapid and specific changes within the Ia+ CD3+ subsets, namely a reduction in the Ia+ CD4+ subset and an increase in the Ia+ CD8+ subset, resulting in a marked decrease in the Ia+ CD4+/Ia+ CD8+ ratio. These changes occurred in association with a reduction in serum T4 and T3 concentration. No significant changes could be detected within the total (predominantly non-activated) CD3+, CD4+ or CD8+ lymphocyte subsets within PB and only a small decrease in the CD4+/CD8+ ratio was demonstrated in IT, following PTU treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420806 TI - Analysis of human TSH receptor gene and RNA transcripts in patients with thyroid disorders. AB - Human TSH receptor (hTSH-R) gene and RNA transcripts were analyzed by Southern and Northern blots in patients with various thyroid disorders, and in tissue cell lines. A 1.4 Kb cDNA encoding the extracellular human TSH-R domain was used as a probe. Southern analysis revealed two constant bands of 11.0 and 5.0 Kb (hTSH-R) in the thyroid and human white cell samples studied, regardless of the disease process. Northern analysis showed a predominant band at about 4.4 Kb in the thyroid tissues but not in non-thyroid tissue or cell lines tested. There were no gene rearrangements or abnormal transcripts in Graves' disease or multinodular goiter samples. In contrast, the labelled cDNA TSH-R probe did not bind to RNA isolated from 1 of 2 papillary cancer samples. A portion of the unique area of the h-TSH receptor (approximately nucleotides 1100-1230) was directly sequenced in thyroid glands from patients with Graves' disease, multinodular goiter, and differentiated thyroid cancer. No mutations or polymorphisms were identified in these samples, as compared to normal thyroid or control placenta, although further definition of sequence variation in other areas of the TSH receptor, as well as in more samples, needs to be performed. The present study indicates the normal patterns of DNA and RNA hybridization in a variety of thyroid tissues and disease states, and demonstrates that pathologic thyroid samples, with the possible exception of thyroid cancer, were not associated with specific nucleotide abnormalities in the unique area of the TSH receptor that was studied. PMID- 1420807 TI - The role of iodine in thyroid autoimmunity: from chickens to humans: a review. AB - Evidence has been presented to support the idea that iodine plays an important role in autoimmune thyroiditis. Excessive amounts induce thyroiditis in genetically susceptible animal strains, while intrathyroidal depletion of iodine prevents disease in strains susceptible to severe thyroiditis. While the mechanisms by which iodine promotes thyroiditis is unknown, several hypotheses have been proposed. (1) T and/or B cells may react specifically to iodinated portions of thyroglobulin (Tg) so that severe iodine depletion renders Tg non immunogenic. (2) A defect in the iodine processing machinery in thyroid epithelial cells of a susceptible person or animal may, in the presence of iodine, result in elevated levels of oxygen or iodine radicals, which could damage membrane lipids or proteins. (3) Defective iodine processing may result in the iodination of lipid or proteins (other than Tg) which could act either as immunogens or polyclonal activators. PMID- 1420808 TI - The role of T lymphocytes in thyroid-associated ophthalmopathy. PMID- 1420809 TI - Role of connective tissue autoimmunity in Graves' ophthalmopathy. AB - Histologic similarities exist between the tissues involved in the extrathyroidal manifestations of Graves' disease, namely ophthalmopathy and pretibial dermopathy. Both conditions are characterized by an accumulation of glycosaminoglycans (GAGs) and an infiltration of lymphocytes. We have shown that interleukin-1 and transforming growth factor-beta, cytokines released by the local inflammatory cell infiltrate, are capable of stimulating GAG synthesis by retroocular and pretibial fibroblasts. Additionally, affected retroocular and pretibial fibroblasts demonstrate an enhanced induction of HLA-DR in response to interferon-gamma treatment and both cell types express the 72 kDa heat shock protein in vivo and in vitro. Retroocular and pretibial fibroblasts from patients with Graves' ophthalmopathy and pretibial dermopathy thus seem to possess unique immunological features that may render them more susceptible to the autoimmune process in Graves' disease. Chronic stimulation of fibroblasts by cytokines released in the local inflammatory milieu may result in excessive GAG production. The accumulation of these hydrophilic mucopolysaccharides, with its associated edema, leads to the clinical manifestations of Graves' ophthalmopathy and pretibial dermopathy. PMID- 1420810 TI - Glycosaminoglycans in thyroid-associated ophthalmopathy. AB - Glycosaminoglycan (GAG) accumulation in the retrobulbar space of patients with thyroid-associated ophthalmopathy (TAO) has been documented in a number of immunohistochemical studies. In order to gain further insight into possible immunopathogenic mechanisms, the influence of humoral immunity on retrobulbar fibroblasts (RF) as GAG producing cells as well as on GAGs themselves was investigated. The effect of lymphocytes on hyaluronic acid (HA) synthesis of RF as well as in turn the influence of RF on lymphocytes were evaluated. In search of methods which would facilitate management of patients with TAO and allow assessment of disease activity, GAGs were determined in both urine and plasma. Immunoglobulin G (IgG) of patients with TAO were found to markedly stimulate the 3H-GAG secretion of RF. Patients with TAO exhibited significantly greater antibody values directed against HA than controls. Preliminary results concerning the influence of lymphocytes on RF indicate a tendency for patients' lymphocytes to increase the synthesis of HA. Furthermore, these lymphocytes in turn were stimulated more by irradiated autologous RF than by irradiated heterologous RF. Urine and plasma GAG determination proved to be suitable for the routine assessment of disease activity and outcome of therapy. In conclusion, GAGs seem to play an important role in the pathogenesis of the disease and their measurement may provide aid to the endocrinological evaluation of patients with TAO. PMID- 1420811 TI - Nature and significance of orbital autoantigens and their corresponding autoantibodies in thyroid-associated ophthalmopathy. AB - There is now considerable evidence that the pathogenesis of thyroid-associated ophthalmopathy is closely linked to the presence of a shared autoantigen(s) in the thyroid and the eye muscle, against which cytotoxic mechanisms are directed. Although the orbital connective tissue is certainly involved in the orbital inflammatory process, a 64 kDa membrane protein expressed by both the eye muscle and the thyroid and recognized consistently by antibodies in the sera of TAO patients, seems to be the most likely target candidate. While its presence in non ocular skeletal muscle is not as well established, more recent data tend to suggest the existence of a 64 kDa molecule in the three tissues. The availability of a cDNA encoding a 572 amino acid protein corresponding to a MW of 63-64 kDa, which may be the same molecule, will allow us to determine more clearly the structural characteristics of the different molecules proposed as targets. The role of the corresponding autoantibodies in the pathogenesis of the eye disease is far less well defined. Whether they play a role in the induction of the ophthalmopathy or only represent helpful markers remains to be clarified. PMID- 1420812 TI - A novel congenital haemostatic defect: combined factor VII and factor XI deficiency. AB - Isolated deficiencies of factors VII and XI are both rare. Not surprisingly, therefore, combined factor VII and XI deficiency has not been reported previously. We report here a kindred with a combined heterozygous deficiency for both factors VII and XI. The proposita is a 28-year-old woman who had both a prolonged prothrombin time (PT) and a prolonged activated partial prothrombin time (APTT) associated with a mild bleeding tendency. Coagulation studies were performed on the six available members of this kindred. The PT and APTT were normal or mildly abnormal in five of these individuals. Factor VII coagulant activity (VII:C) varied from 0.33 to 0.77 units/ml in affected subjects. In contrast, the concentration of factor VII-related antigen for the six individuals ranged from 0.68 to 2.10 units/ml. Comparable factor VII:C levels were obtained when each subject's plasma was tested with either a rabbit or a human thromboplastin reagent. Factor XI coagulant activity was less than 0.5 units/ml in three of the six subjects and normal (approximately 1.0 units/ml) in the other three. The concentrations of thrombin-antithrombin-III and prothrombin fragment 1.2 were within normal limits for all individuals. In addition to being associated with heterozygous factor XI deficiency, the abnormal factor VII molecule in the plasma of affected individuals in this kindred appears to represent a newly described mutation. This is suggested by the pattern of reactivity with thromboplastin from different species, the normal tissue factor binding and the bleeding tendency in heterozygous individuals in this kindred. PMID- 1420813 TI - Human fibrinogen heterogeneity: the COOH-terminal residues of defective A alpha chains of fibrinogen II. AB - Fibrinogen fraction I (340 kDa) and fraction II (305 kDa) were isolated by glycine precipitation. The subunit chains of the two fractions were separated, after reduction, by reverse-phase high performance liquid chromatography. The amino acid compositions of the B beta and tau chains of fibrinogen II were identical with those of fibrinogen I. In contrast, the A alpha chains of fibrinogen II were composed of two populations, one comprising homogeneous, intact A alpha chains and the other consisting of heterogeneous, deficient A alpha chains (A alpha' chains) of lengths varying according to the sizes of their COOH-terminal defects. The molar ratio of the A alpha to the A alpha' chains in fibrinogen II was 1.16:1. The amino acid composition and sequence analyses of the TPCK-trypsin peptides derived from the A alpha' chains revealed that the COOH terminal residues of the A alpha' chains were mainly Asn-269, Gly-297 and Pro 309. These results indicate that the fibrinogen II molecule is asymmetrical and can be represented by the formula (A alpha) (A alpha')(B beta)2(tau)2 and that fibrinogen II cannot be a plasmin degradation product of fibrinogen I. PMID- 1420814 TI - Behaviour of tissue plasminogen activator, plasminogen activator inhibitor 1 and their complex in various disease states. AB - Plasma levels of tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen and t-PA/PAI-1 complex were measured in plasmas from 18 healthy subjects and 75 patients with various diseases (28 patients with haematological malignancies, 20 with thrombotic diseases, five with infectious diseases, four with liver diseases, ten with bleeding disorders and eight miscellaneous conditions). In addition, we studied ten patients with bleeding disorders after DDAVP infusion and 18 healthy subjects after venous occlusion. Plasma levels of t-PA antigen, PAI-1 antigen and t-PA/PAI-1 complex were increased in the patients compared with the healthy subjects. t-PA/PAI-1 complex levels correlated well with t-PA antigen levels and molar concentrations of t-PA antigen were similar to those of the t-PA/PAI-1 complex. Venous occlusion induced an increase in both t-PA antigen and PAI-1 antigen and the molar concentration of the t-PA/PAI-1 complex was equivalent to that of t-PA antigen. Following DDAVP infusion, the levels of t-PA antigen and t-PA/PAI-1 complex increased but PAI-1 antigen levels decreased, and the increase of t-PA antigen was greater than that of t-PA/PAI-1 complex. These findings indicate that PAI-1 antigen exceeds t-PA antigen in healthy subjects and in patients with various diseases. We conclude that part of the t-PA/PAI-1 complex is rapidly cleared from the circulation and that free t-PA increases after DDAVP infusion. PMID- 1420815 TI - Membrane fluidity and platelet aggregation: dibucaine permits ristocetin-induced platelet aggregation with low-molecular-weight von Willebrand multimers. AB - The effects of brief incubation of platelets with dibucaine were studied. Membrane fluidity was increased after incubation with 1 mM dibucaine for 1 min as determined by fluorescence polarization. Platelet aggregation was increased when ristocetin was employed as modulator and normal plasma used as a source of von Willebrand factor (vWF). In contrast, aggregation was decreased with botrocetin. After cryoprecipitation the supernatant, which contained predominantly low molecular-weight vWF multimers, was effective with ristocetin only after prior incubation of the platelets with dibucaine. This indicates that low-molecular weight vWF multimers can also support ristocetin-induced aggregation when the membrane fluidity is increased. This idea was supported by the use of plasma from a patient with von Willebrand disease type IIa. Being a multimeric protein, von Willebrand factor contains multiple binding sites for glycoprotein Ib (GP Ib). GP Ib-dependent aggregation by agents that do not contain multiple binding sites, i.e. wheat germ agglutinin or polyclonal antibodies to GP Ib, was decreased after brief incubation with dibucaine. These observations are discussed in relation to the hypothesis that the increased membrane fluidity allows an increased number of GP Ib molecules to bind to each vWF multimer. PMID- 1420816 TI - Antiphospholipid antibodies and thrombosis in systemic lupus erythematosus: comparison of three lupus anticoagulant assays and anticardiolipin ELISA in 188 patients. AB - The presence of antiphospholipid antibodies (aPL) in 188 unselected patients with systemic lupus erythematosus was studied using the recalcification time, kaolin clotting time (KCT), dilute Russell's viper venom time (dRVVT) and anticardiolipin ELISA (aCL) to identify patients with a high or low risk of thrombosis among patients with aPL. aPL were detected by at least one method in 104 (55%) of the patients. Despite heterogeneity, lupus anticoagulant (LA) methods correlated reasonably well with each other (r = 0.736-0.968), but poorly with aCL (r = 0.241-0.549). Positivity in LA assays and immunoglobulin G (IgG) aCL were associated with patients who experienced thrombosis (P less than 0.001 for all assays). Patients with both LA and aCL had experienced thrombosis more often than those having only one (odds = 6.3, P less than 0.001). When patients with aPL were ranked by relative strength of the finding and divided into tertiles, a history of thrombosis was associated with membership in the strongest tertile of at least one assay (odds = 4.2, P = 0.002). LA and aCL had similar sensitivities for thrombosis (61% and 63%, respectively), but LA was more specific than aCL (79% vs 53%). The best combination of two assays was KCT with dRVVT (61% sensitivity, 87% specificity). Maximal sensitivity (71%) for thrombosis could be achieved by adding IgG-aCL to these two assays, but specificity was lower (73%). In conclusion, a high thrombotic risk among patients with aPL was indicated by the simultaneous presence of both LA and aCL, strongly positive aPL, and, among aCL, IgG-class antibodies. PMID- 1420817 TI - Molecular study of von Willebrand disease: identification of potential mutations in patients with type IIA and type IIB. AB - The defective von Willebrand Factor (vWF) in type IIA von Willebrand disease (vWD) has decreased binding affinity for platelet membrane glycoprotein Ib (GPIb) while in type IIB vWD, the abnormal vWF has increased affinity for this receptor. Segments of exon 28 of the vWF gene were amplified by the polymerase chain reaction and sequenced in two patients with type IIA and two patients with type IIB vWD. One type IIB patient showed an arginine to tryptophan substitution at amino acid residue 543 in the mature vWF and the other patient had a valine to methionine change at residue 553. Including these two new cases, substitutions at residues 543 and 553 now account for more than half of the documented mutations in patients with type IIB vWD. One patient with type IIA vWD showed an isoleucine to threonine change at amino acid 865. This substitution has been reported in another patient with type IIA vWD. The other patient showed a novel proline to serine change at residue 885. The C to T nucleotide transition which causes the amino acid change was not found in over 100 normal chromosomes tested by allele specific oligonucleotide hybridization and was linked to type IIA vWD in the family. This potential mutation is more carboxyterminal in the vWF subunit than other reported mutations in type IIA vWD. It is apparent that mutations associated with type IIA vWD are not as tightly grouped as defects in type IIB vWD, supporting the evidence that the type IIA vWD phenotype is generated by diverse mechanisms. PMID- 1420818 TI - Quantitative assay of the carbohydrate in urokinase-type plasminogen activator by lectin-enzyme immunoassay. AB - We developed an enzyme immunoassay (EIA) for the measurement of Asn302-linked carbohydrate in urokinase-type plasminogen activator (u-PA) using peroxidase (HRP)-labelled lectins. u-PA antigen in the sample was immunologically bound to microtitre plate wells by anti-u-PA IgG and the binding of HRP-labelled lectins [Con A (Concanavalin A), WGA (wheat germ agglutinin), PNA (peanut agglutinin), CSA (Scotch broom), GS-I (Groffonia simplicifollia) and SBA (soybean agglutinin)] to the carbohydrate of u-PA was measured. The lectin-EIA was dose-dependent in the range 6-6000 IU/ml of u-PA using Con A and WGA. The assay did not detect the carbohydrate of bovine albumin, ovalbumin, human albumin, plasminogen, tau globulin and fibrinogen. The binding of HRP-labelled Con A and WGA to the carbohydrate of u-PA was specifically inhibited by alpha-methylmannose and N acetylglucosamine respectively. Endo F treatment of the carbohydrate of u-PA decreased the binding of Con A and WGA. The carbohydrate of u-PA obtained from chest fluid, ascites and U937 cell culture medium reacted with Con A and WGA by this assay forming a band in the 55 kDa region. These results suggest that the lectin-EIA method is suitable for the assay of the carbohydrate in the B-chain of u-PA. PMID- 1420819 TI - The present status of tissue factor pathway inhibitor. AB - Tissue factor pathway inhibitor (TFPI) is the factor Xa-dependent inhibitor of the factor VIIa/tissue factor complex. The plasma concentration of this 276 amino acid, 40 kDa glycoprotein is normally about 100 ng/ml. There are three intravascular pools of TFPI: 50-90% is on the endothelium, 10-50% is in plasma and less than 2.5% is in platelets. The TFPI in plasma is mainly associated with lipoproteins-only about 5% is free TFPI. The lipoprotein-associated TFPI seems to be of less anticoagulant effect than the free TFPI. Both unfractionated heparin, low-molecular-weight heparins and pentosan polysulphate induce release of TFPI after intravenous injection, whereas dermatan sulphate does not. The interactions with TFPI account for a considerable amount of the anticoagulant effect of heparin. Studies have shown increased TFPI levels in plasma from patients with advanced malignancy and in subjects with fatal DIC or septicaemia. The reason for this is unknown. For measuring the anticoagulant activity of TFPI in plasma, end point or antigen assays may be less useful than the clotting assay with dilute tissue factor. Animal studies indicate that the main physiological role of TFPI is the inhibition of small amounts of tissue factor. TFPI is probably essential for a normal haemostatic balance. PMID- 1420820 TI - Venous thromboembolism and cancer. AB - The literature was reviewed in an attempt to determine whether patients with cancer have an increased risk of venous thromboembolism, i.e. deep vein thrombosis and pulmonary embolism. From case reports it was apparent that various thromboembolic or thrombophlebitic manifestations may be found in a small number of patients, although it is possible that not all cases belong to the same clinical or pathogenetic entity. In clinical series it was found that the risk of postoperative venous thromboembolism was increased in cancer patients, but the possibility that this was due to associated risk factors, rather than to the mere presence of a tumour, could not be excluded. Little is known about patients not undergoing surgery. Retrospective postmortem studies have found more thrombi in patients with malignancy, but a prospective study failed to demonstrate an association between malignancy and pulmonary embolism. It is possible that different types of cancer show various degrees of association with venous thromboembolism. We conclude that further studies should be performed to provide a firm clinical and pathoanatomical basis for investigations into the pathogenesis of venous thromboembolism. PMID- 1420821 TI - Haemostatic effects in vivo after snakebite by the red-necked keelback (Rhabdophis subminiatus). AB - We describe a patient who developed a severe coagulopathy after being bitten by a red-necked keelback snake (Rhabdophis subminiatus), a species which is generally considered non-venomous. The patient's blood was incoagulable due to complete depletion of fibrinogen. Comprehensive coagulation studies were performed to identify the mechanism(s) by which the snake toxin caused the coagulopathy. It was found to contain a potent prothrombin activator, probably an activator of protein C and possibly also a factor X activating enzyme. The fibrinolysis was secondary to intravascular fibrin formation; there were no indications for a direct fibrinogenolytic activity in the snake toxin. Remarkably, there was virtually no consumption of antithrombin III, despite extensive thrombin formation; this feature appears to be not uncommon after snake bites, but is still unexplained. PMID- 1420822 TI - Dental surgery in patients with severe factor XI deficiency without plasma replacement. AB - Bleeding following dental extraction is frequently the first manifestation of severe factor XI deficiency. Safe oral surgery has previously been performed in such patients by using plasma replacement therapy with or without concomitant administration of antifibrinolytic agents. The aim of this study was to determine whether such patients can undergo safe dental extractions using only an antifibrinolytic agent. The study group consisted of 19 patients with severe factor XI deficiency (factor XI:C level less than 14 U/dl) who had previously bled following dental extractions (14 patients) or other trauma (five patients). Tranexamic acid, 1 g q.i.d., was given from 12 h before surgery, until 7 days afterwards. No excessive bleeding was observed following dental extractions. One patient had slight oozing after 3 days which ceased spontaneously. Thus, plasma replacement no longer appears necessary for patients with severe factor XI deficiency requiring dental extractions. PMID- 1420823 TI - Prothrombin fragment F1 + 2 and thrombin-antithrombin III complex are useful markers of the hypercoagulable state in atrial fibrillation. AB - It is well known that atrial fibrillation (AF) is one of the most important diseases that predispose patients to thrombosis. We have attempted to identify patients with AF in the hypercoagulable state by measuring molecular markers such as thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (PTF) and determining the effect of antithrombotic therapy on these markers; 83 patients with AF were studied. Increased levels of plasma TAT and PTF were more frequently observed in patients with AF and associated mitral stenosis than in patients with AF alone. In cases of AF without mitral stenosis, plasma levels of TAT and PTF were significantly lower in those patients receiving antithrombotic agents (aspirin or warfarin) than in those receiving no antithrombotic agents. Furthermore, plasma levels of PTF were significantly lower in patients given warfarin than in those receiving aspirin. These results suggest that (1) patients with AF and mitral stenosis who are not given warfarin are in an extremely hypercoagulable state and (2) some patients with AF without mitral stenosis who are not given antithrombotic agents are also moderately hypercoagulable. In vivo activation of blood coagulation was more effectively controlled in patients receiving warfarin than in those taking aspirin. PMID- 1420824 TI - Thrombolysis using consecutive high dose bolus and infusion of alteplase in a patient with acute massive pulmonary embolism. AB - We describe the successful use of a novel dosage regimen of alteplase in a 77 year-old man with massive acute pulmonary embolism in the presence of a relative contraindication (recent cranial surgery). An intravenous alteplase bolus of 50 mg was administered, followed 40 min later by a 50 mg infusion over 2 h. Pulmonary arteriography showed a considerable increase in intraluminal filling of thrombotically occluded vessels as a result of alteplase administration, and was accompanied by marked clinical improvement. Peak alteplase plasma concentration after the bolus was 5.5 micrograms/ml, and the steady state concentration during infusion was 0.52 micrograms/ml. Detailed monitoring of haemostasis parameters showed elevated endogenous fibrinolytic activity at baseline, very high levels of fibrin degradation products during treatment resulting from lysis of an extensive thrombus mass, moderate fibrinogenolysis compared to fibrinolysis, long plasma half-lives of fibrin(ogen) degradation products (9.2-11.0 h), and increased thrombin generation. There were no bleeding side-effects. The regimen combines the advantages of rapid onset (bolus) and maintained potency (infusion) of thrombolytic effect in pulmonary embolism. PMID- 1420825 TI - A comparison of the plasminogen activator activity units of urinary-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA). AB - The earliest tissue plasminogen activator (t-PA) preparations prepared from melanoma cells were expressed in urinary-type plasminogen activator (u-PA) units of activity using the u-PA International Standard (66/46). This report describes a comparison between u-PA and t-PA units by various types of fibrin plate procedure using both human and bovine fibrin. Within the biometric limits of this procedure it was found that the potency ratio of u-PA/t-PA was 3.5 (human fibrin), 5.29 (enriched bovine fibrin) and 4.6 (crude bovine fibrin). Specific activity figures of approximately 100,000 IU/mg for pure t-PA using the urokinase standard (66/46) would convert to approximately 350,000-530,000 IU/mg using the International Standards for t-PA (83/517 and 87/670). This latter figure is compatible with the reported specific activity for purified preparations of recombinant t-PA. PMID- 1420826 TI - Intra-cardial thrombosis with systemic and pulmonary embolism as main symptoms in a patient with protein S deficiency. AB - This report describes the unusual occurrence of both left and right atrial thrombosis with peripheral arterial and pulmonary embolism, respectively, as presenting symptoms of congenital protein S deficiency in a 31-year-old man. The coagulation study performed in the coumarin-treated propositus indicated a heterozygous protein S state. The finding of reduced free protein S antigen and protein S activity levels with normal total protein S and C4B-bp levels in five other family members (father, sister, and three relatives on the paternal side) confirmed the inherited nature of the defect. Since there is an increased frequency of arterial thrombosis in patients suffering from protein S deficiency, any case of idiopathic intra-cardial thrombosis requires careful haemostatic screening. In addition, the possibility of intra-cardial thrombosis should be considered in any thromboembolic event seen in inherited protein S deficiency. PMID- 1420827 TI - Use of thermal imaging to monitor crural thrombolysis. AB - Intra-arterial thrombolysis is increasingly being used as the treatment of choice in selected cases of critical limb ischaemia. At present angiography is the established method of monitoring the progress of thrombolysis. We report a case in which thermal imaging was used in conjunction with angiography to monitor the effects of thrombolysis. PMID- 1420828 TI - Evidence of discrepant commercial ISI assignment. PMID- 1420829 TI - Circadian rhythm of plasma beta-thromboglobulin in healthy human subjects. PMID- 1420830 TI - [Suitability of capacitive sensors for measuring relative humidity in anesthetic gas systems]. AB - A capacitive sensor was tested for its suitability for measuring relative humidity in an anaesthetic gas circuit. The valvo sensor PH1 was tested using various different anaesthetic gas mixtures. Measuring accuracy was influenced neither by such volatile anaesthetics as isoflurane and halothane, nor by oxygen or nitrous oxide. The response time of the sensor depends on its position within the gas, and in the most favourable case is about 3 minutes. The sensor is readily incorporated within an existing gas circuit. The linearity of the characteristic curve must be corrected by external electronic compensation to avoid measuring problems in the lower humidity range. PMID- 1420831 TI - [Automatic tracking system for laser surgery of the human cornea]. AB - An automatic, closed loop, real-time tracking device is described. The purpose of this device is, despite movements of the eye, to keep the laser beam correctly on target while performing corneal surgery. This type of laser surgery, is employed specifically to ablate some of the cornea to correct myopia, hyperopia and astigmatism. PMID- 1420832 TI - [Morphological and numerical studies of the stress compatibility of patella implants]. AB - Failure of total knee arthroplasty is relatively often caused by problems of the patellofemoral replacement. The purpose of this study was to analyze the distribution of stresses within an anatomical patella and the changes in stress distribution after patellar resurfacing with a Miller-Galante I patellar implant using two- and three dimensional finite element models (FEM). To assess validity, FEM results were compared with morphological findings from contact radiographs and densitographs. Internal orientation of bone trabeculae is in good agreement with the orientation of theoretically calculated principal stresses. Almost unchanged principal tensile stresses after implantation, together with the lack of extreme stress peaks within the cancellous bone ensure stress compatibility of the implant. In the case of a firmly seated implant with good bone ingrowth, increased von Mises stresses are found near the fixation peg/plate junction. Their relevance for improved bone ingrowth near this part of the interface is emphasized. At the same time, material failure at the peg/plate junction can be better understood. An analysis of the early postoperative period assuming nonlinear interface conditions failed to demonstrate an uniform distribution of normal and tangential interface forces. PMID- 1420833 TI - Linear regression analysis based on Buckley-James estimating equation. AB - In this note we consider the problem of drawing inference about the regression parameters in a linear model with survival data. A simple procedure based on the Buckley-James (1979, Biometrika 66, 429-436) estimating equation is proposed and illustrated with an example. PMID- 1420834 TI - Blocked arteries and multivariate regression. AB - Ultrasound blood flow waveforms may be used in the diagnosis of arterial occlusive disease in human legs. We develop a statistical model to predict disease severity, conditional on the ultrasound data and some training data. It belongs to the class of models known as seemingly unrelated regressions, for which the Bayesian predictive density function cannot be evaluated analytically. Allowing for missing components of response vectors in the training data, we describe a first-order approximation to the predictive density, based on a Bayes estimate of the precision matrix. This approximation is then used to generate cross-validated predictions of disease severity in a set of 31 patients. We conclude with a discussion of the results. PMID- 1420835 TI - Testing the effect of treatment in experiments with correlated binary outcomes. AB - This paper considers the problem of testing for treatment effect in a randomized experiment with correlated binary outcomes, representing success or failure for different "parts" of a randomized unit. Attention is restricted to tests that are based on a summary score for each individual randomized, and thus are valid regardless of the precise nature of the correlation among parts. The focus is on the efficiency of such tests under various correlation structures, with special emphasis on the case in which the correlation among parts within an individual differs across treatment groups. A class of summary score statistics is defined, and optimal testing is discussed for some simple situations. Three potential general-purpose tests also are described: (1) the ratio estimate test discussed by Henderson et al. (1988, Controlled Clinical Trials 9, 189-205); (2) a modified ratio estimate test with adjusted weighting based on the within-individual correlation between parts; (3) a test defined by applying the Mantel-Haenszel procedure to the proportion of individuals with at least one failure, stratifying by the number of parts. For these general-purpose tests, numerical calculations of asymptotic efficiency are presented under a wide range of designs and correlation structures. On the basis of these results, some practical recommendations for choosing a test are made. PMID- 1420836 TI - Multivariate methods for clustered binary data with multiple subclasses, with application to binary longitudinal data. AB - Clustered binary data occur frequently in biostatistical work. Several approaches have been proposed for the analysis of clustered binary data. In Rosner (1984, Biometrics 40, 1025-1035), a polychotomous logistic regression model was proposed that is a generalization of the beta-binomial distribution and allows for unit- and subunit-specific covariates, while controlling for clustering effects. One assumption of this model is that all pairs of subunits within a cluster are equally correlated. This is appropriate for ophthalmologic work where clusters are generally of size 2, but may be inappropriate for larger cluster sizes. A beta-binomial mixture model is introduced to allow for multiple subclasses within a cluster and to estimate odds ratios relating outcomes for pairs of subunits within a subclass as well as in different subclasses. To include covariates, an extension of the polychotomous logistic regression model is proposed, which allows one to estimate effects of unit-, class-, and subunit-specific covariates, while controlling for clustering using the beta-binomial mixture model. This model is applied to the analysis of respiratory symptom data in children collected over a 14-year period in East Boston, Massachusetts, in relation to maternal and child smoking, where the unit is the child and symptom history is divided into early-adolescent and late-adolescent symptom experience. PMID- 1420837 TI - A parametric family of correlation structures for the analysis of longitudinal data. AB - In epidemiological settings, we are often faced with numerous short time series, and a parsimonious parametrization of the correlation structure is desired in order to optimize the efficiency of the estimation procedure. We propose a damped exponential correlation structure for modeling multivariate Gaussian outcomes. The correlation between two observations separated by s units of time is modeled as gamma s theta, where gamma is the correlation between elements separated by one s-unit, and theta is a damping parameter. For (theta = 0), (theta = 1), and theta----infinity), the correlation structures of compound symmetry, first-order autoregressive, and first-order moving average processes are obtained. Although the AR(2) dependency structure, and the combination of random effects and AR(1) errors are not special cases of the proposed parametric family, these structures can be well approximated within the family for short time series. Maximum likelihood methods for parameter estimation and interpretations of intermediate models (0 less than theta less than 1) are discussed in the context of modeling pulmonary function in an adult population in The Netherlands and T-cell subsets in homosexual men infected with human immunodeficiency virus Type I. PMID- 1420838 TI - Modelling balanced longitudinal data: maximum likelihood estimation and analysis of variance. AB - For linear models, assuming a within-experimental-units covariance structure that incorporates errors of measurement, serial correlation, and variation between units, results on explicit estimation of regression parameters are used to simplify maximum likelihood estimation of covariance parameters. The use of an analysis of variance table as a simpler alternative to likelihood inference is illustrated with two examples. PMID- 1420839 TI - Exchangeability in multivariate Markov chain models. AB - Time-homogeneous Markov chain models with state space [0, 1]k are useful in analysis of binary follow-up data on k individuals that interact. The number of parameters increases exponentially with k so more restrictive models are imperative for statistical inference. The hypothesis that the matrix of transition probabilities is invariant under permutation of individuals is discussed. It is shown that if individuals are exchangeable, then the process counting the number of individuals occupying a given state is a Markov chain. This reduction of data is sufficient if either at most a single individual may change state between two consecutive time points or if a state is absorbing. Similar results are obtained for exchangeability within two subgroups. Inference in the multivariate process reduces to a univariate problem if individuals are independent given the group's previous response. It is shown how conditional independence could be tested assuming exchangeability. The different hypotheses re examined in an analysis of the occurrence of bacteria in milk samples of Danish dairy cattle. PMID- 1420840 TI - Sequential monitoring for comparison of changes in a response variable in clinical studies. AB - The spending function approach proposed by Lan and DeMets (1983, Biometrika 70, 659-663) for sequential monitoring of clinical trials is applied to situations where comparison of changes in a continuous response variable between two groups is the primary concern. Death, loss to follow-up, and missed visits could cause follow-up measurements to be right-censored or missing for some participants. Furthermore, the probability of being censored may be dependent on the parameter value of the response variable (informative censoring). We propose to compare treatment effects by comparing areas under the expected response change curves between the two groups. When the response curves are linear as a function of time in both groups, this comparison is equivalent to comparing the rates of change in the response variable. Covariances of the sequential test statistics are derived. Conditions for having independent increments are presented. For studies designed to evaluate long-term treatment effects, spending functions obtained by shifting the usual spending functions (Kim and DeMets, 1987, Biometrika 74, 149-154) to the right and then rescaling to the remaining interval are also proposed. Such a shifted spending function is applied to the monitoring plan for the Lung Health Study (Anthonisen, 1989, American Review of Respiratory Diseases 140, 871-872). PMID- 1420841 TI - Use of external rates in nested case-control studies with application to the international radiation study of cervical cancer patients. AB - A method is proposed for analysis of nested case-control studies that combines the matched comparison of covariate values between cases and controls and a comparison of the observed numbers of cases in the nesting cohort with expected numbers based on external rates and average relative risks estimated from the controls. The former comparison is based on the conditional likelihood for matched case-control studies and the latter on the unconditional likelihood for Poisson regression. It is shown that the two likelihoods are orthogonal and that their product is an estimator of the full survival likelihood that would have been obtained on the total cohort, had complete covariate data been available. Parameter estimation and significance tests follow in the usual way by maximizing this product likelihood. The method is illustrated using data on leukemia following irradiation for cervical cancer. In this study, the original cohort study showed a clear excess of leukemia in the first 15 years after exposure, but it was not feasible to obtain dose estimates on the entire cohort. However, the subsequent nested case-control study failed to demonstrate significant differences between alternative dose-response relations and effects of time related modifiers. The combined analysis allows much clearer discrimination between alternative dose-time-response models. PMID- 1420842 TI - Semiparametric estimation of random effects using the Cox model based on the EM algorithm. AB - Consider a survival experiment where individuals within a certain subset of the population share a common, unobservable, random frailty. Such a frailty could be an unobservable genetic or early environmental effect if individuals were in sibling groups or an environmental effect if individuals were grouped by households. Suppose that if the frailty, omega, is known, the Cox proportional hazards model for the observable covariates is valid with the consequence of the random effect being a multiplicative factor on the hazard rate. Assuming tht the random frailties follow a gamma distribution, estimates of the fixed and random effects are obtained by using an EM algorithm based on a profile likelihood construction. The method developed is applied to the Framingham Heart Study to examine the risks of smoking and cholesterol levels, adjusting for potential random effects. PMID- 1420843 TI - A statistical distribution with an unbounded hazard function and its application to a theory from demography. AB - We introduce a statistical distribution with hazard function mu(t) proportional to (psi-t)beta-1 for 0 less than or equal to t less than psi and shape parameter beta satisfying 0 less than beta less than 1. This hazard function is suggested by a theory of aging in demography. We discuss properties of this distribution and maximum likelihood estimates of its parameters. Mixture distributions are considered to account for pooling across dissimilar populations. This model is compared with the Gompertz and generalized Pareto distributions and used to estimate a finite limit on human lifespan based on the survival of a group of female centenarians. PMID- 1420844 TI - Proportional hazards model with covariates subject to measurement error. AB - When covariates of a proportional hazards model are subject to measurement error, the maximum likelihood estimates of regression coefficients based on the partial likelihood are asymptotically biased. Prentice (1982, Biometrika 69, 331-342) presents an example of such bias and suggests a modified partial likelihood. This paper applies the corrected score function method (Nakamura, 1990, Biometrika 77, 127-137) to the proportional hazards model when measurement errors are additive and normally distributed. The result allows a simple correction to the ordinary partial likelihood that yields asymptotically unbiased estimates; the validity of the correction is confirmed via a limited simulation study. PMID- 1420845 TI - Estimating the probability of toxicity at the recommended dose following a phase I clinical trial in cancer. AB - The problem of point and interval estimation following a Phase I trial, carried out according to the scheme outlined by O'Quigley, Pepe, and Fisher (1990, Biometrics 46, 33-48), is investigated. A reparametrization of the model suggested in this earlier work can be seen to be advantageous in some circumstances. Maximum likelihood estimators, Bayesian estimators, and one-step estimators are considered. The continual reassessment method imposes restrictions on the sample space such that it is not possible for confidence intervals to achieve exact coverage properties, however large a sample is taken. Nonetheless, our simulations, based on a small finite sample of 20, not atypical in studies of this type, indicate that the calculated intervals are useful in most practical cases and achieve coverage very close to nominal levels in a very wide range of situations. The relative merits of the different estimators and their associated confidence intervals, viewed from a frequentist perspective, are discussed. PMID- 1420846 TI - The efficiency of a weighed log-rank test under a percent error misspecification model for the log hazard ratio. AB - For comparison of two survival distributions, it is natural to use a weighted log rank test with weight function given by the log hazard ratio function that is anticipated a priori. This paper investigates the efficiency of this test when the a priori estimate of the log hazard ratio is subject to a specified percentage error. The test is shown to be the maximum efficiency robust test over the class of alternatives in question and a simple expression for the maximum efficiency is established. PMID- 1420847 TI - Starting D-optimal designs for batch kinetics studies of enzyme-catalyzed reactions in the presence of enzyme deactivation. AB - This paper describes a strategy for the starting experimental design of experiments required by general research in the field of biochemical kinetics. The type of experiments that qualify for this analysis involve batch reactions catalyzed by soluble enzymes where the activity of the enzyme decays with time. Assuming that the catalytic action of the enzyme obeys a Michaelis-Menten rate expression and that the deactivation of the enzyme follows a first-order decay, the present analysis employs the dimensionless, integrated form of the overall rate expression to obtain a criterion (based on the maximization of the determinant of the derivative matrix) that relates the a priori estimates of the parameters with the times at which samples should be withdrawn from the reacting mixture. The analysis indicates that the initial concentration of substrate should be as large as possible, and that the samples should be taken at times corresponding to substrate concentrations of approximately 2/3, 1/4, and I/epsilon of the initial concentration (where epsilon should be as large as possible). PMID- 1420848 TI - Marginal models for correlated binary responses with multiple classes and multiple levels of nesting. AB - A model for correlated binary data is presented. Marginal probabilities and odds ratios are allowed to have general regression structures that include multiple classes and multiple levels of nesting. Estimation is done through the generalized estimating equations approach of Liang and Zeger (1986, Biometrika 73, 13-22). They are contrasted with conditional models and recommendations for choosing between the two are given. Examples from genetic epidemiology are presented. PMID- 1420849 TI - Maximum likelihood estimation for interval-censored data using a Weibull-based accelerated failure time model. AB - The accelerated failure time regression model is most commonly used with right censored survival data. This report studies the use of a Weibull-based accelerated failure time regression model when left- and interval-censored data are also observed. Two alternative methods of analysis are considered. First, the maximum likelihood estimates (MLEs) for the observed censoring pattern are computed. These are compared with estimates where midpoints are substituted for left- and interval-censored data (midpoint estimator, or MDE). Simulation studies indicate that for relatively large samples there are many instances when the MLE is superior to the MDE. For samples where the hazard rate is flat or nearly so, or where the percentage of interval-censored data is small, the MDE is adequate. An example using Framingham Heart Study data is discussed. PMID- 1420850 TI - On estimating standardized risk differences from odds ratios. AB - An estimator proposed by Greenland and Holland (1991, Biometrics 47, 319-322) for a standardized risk difference parameter is shown to be a maximum likelihood estimator if the consistent estimator of the common odds ratio is appropriately chosen. The statistical problem under consideration is reparameterized. Likelihood equations are derived. PMID- 1420851 TI - On informative and random dropouts in longitudinal studies. PMID- 1420853 TI - A theory of site distribution of melanomas: Queensland, Australia. AB - Although sun exposure is believed to be associated causally with cutaneous melanoma, the high incidence on less sun-exposed areas such as the back, as well as on chronically exposed sites such as the face, suggests that the association with sunlight is less straightforward than for other skin cancers. To explain this enigmatic site distribution, a theory of site-dependent susceptibility of melanocytes to malignant transformation is proposed. As possible evidence, all melanomas diagnosed in the state of Queensland, Australia, over a one-year period were surveyed for histologic evidence of benign melanocytic nevus cells adjacent to the melanoma, and analyzed according to anatomic distribution. Results showed a regional variation in the proportion of melanomas with adjacent nevi not explicable by regional variation in nevus density, which suggests that there is a varying susceptibility of nevi to malignant change. Given that nevus cells are equivalent to melanocytes, this finding would support the hypothesis that melanocytes at-large have a differential response to the mitogenic stimulus of sunlight according to anatomic site. PMID- 1420852 TI - Carotenoids, retinol, and vitamin E and risk of proliferative benign breast disease and breast cancer. AB - We investigated the relationship between serum levels of retinol, beta-carotene, alpha-carotene, lycopene, alpha-tocopherol, and gamma-tocopherol as well as intakes of retinol, carotene, and vitamin E and the risks of breast cancer and proliferative benign breast disease (BBD) in a case-control study of postmenopausal women in the Boston, MA (United States) area. Serum nutrient data were available for 377 women with newly diagnosed stage I or II breast cancer and 173 women with proliferative BBD. Controls were 403 women who were evaluated at the same institutions but did not require a breast biopsy or whose biopsy revealed nonproliferative BBD. We observed no significant associations between serum levels of these micronutrients and risk of proliferative BBD or breast cancer. The risk of breast cancer was decreased among women in the highest quintile of intake of vitamin E from food sources only (odds ratio [OR] for the highest quintile = 0.4, 95 percent confidence interval [CI] = 0.2-0.9; P, trend across quintiles = 0.02) but less so for total vitamin E intake including supplements (OR = 0.7, CI = 0.4-1.3; P, trend = 0.07). PMID- 1420854 TI - Atypical hyperplasia and breast cancer risk: a critique. AB - The purpose of this paper is to examine critically the evidence that atypical hyperplasia (AH) is a risk factor for breast cancer. First, we appraised studies that have examined the association between AH and breast cancer risk for their adherence to widely accepted standards for the conduct of research. Second, we examined the available evidence to determine the plausibility of an association between AH and breast cancer risk using the guidelines proposed by Bradford Hill. A total of 18 studies (11 cohort studies, two case-control studies, and five cross-sectional studies) were found that were published in the English language from January 1960 to March 1992 that examined the association of AH as a distinct entity and breast cancer risk. A systematic approach was adopted to examine the collected studies for their adherence to methodologic standards, which showed wide variation among studies. A meta-analysis was carried out, based on a total sample size of 182,980 women. Of 16 studies that gave point estimates of risk, 14 exceeded unity and 12 were significantly different from unity. The pooled estimate from all studies of the association between AH and breast cancer, gave an overall odds ratio (OR) of 3.67 (95 percent confidence interval = 3.16-4.26). The test of the hypothesis of homogeneous association was rejected (chi 2 = 151.6, df = 14, P < 0.0001), indicating significant variability among the ORs of individual studies. The conclusions from the application of the Bradford Hill criteria indicated strongly that AH is a risk factor for breast cancer. PMID- 1420855 TI - Childhood cancer among Swedish twins. AB - The risk of childhood cancer was evaluated among 35,582 twins born in Sweden between 1952 and 1967. Cancers were identified through linkage with national cancer and mortality registries. Overall, 59 childhood cancers and 41 deaths from cancer occurred before the age of 16. For both sexes combined, the cancer incidence was similar to that in the general population of primarily single-born children (number observed/number expected [O/E] = 1.0, 95 percent confidence interval [CI] = 0.7-1.2). For males under age five, cancer incidence was reduced significantly (O/E = 0.3, CI = 0.1-0.7). There was a substantial increase in all cause mortality among twins (O/E = 3.7), attributable to a high mortality during the first year of life. Excluding this first year, the O/E for death (all causes) was 1.1 (CI = 1.0-1.3). For cancer mortality of both sexes, the O/E was 0.9 (CI = 0.6-1.2), with no significant reduction of risk in any sex-age group. We conclude that with the possible exception of males aged 0-4 years, the childhood cancer risk of twins appears similar to that of singletons. PMID- 1420856 TI - Urban-rural differences in the management of breast cancer. AB - We conducted a population-based study with medical-record review of breast cancer patients as part of a larger study of an oncology outreach program to improve cancer management for rural patients within their community hospital. This analysis compares the breast cancer care received by the rural population before the oncology outreach program with that of the contiguous urban population. All 1986-87 cases in selected Illinois (United States) counties were identified using the Illinois State Cancer Registry. Data were obtained by hospital record audit and physician survey. Case follow-back was 98 percent complete. Rural cases were evaluated separately when they were diagnosed in an urban facility. State-of-the art management was defined by the 1986-87 Physician Data Query and included diagnostic evaluation, prognostic evaluation, and stage-specific treatment. A summary variable incorporated whether or not the most appropriate management was offered. Compared with urban cases, rural cases diagnosed in rural hospitals were less likely to have staged tumors and more likely to have node dissections. Rural cases traveling to urban centers were less likely to have limited surgery, hormone therapy, and a biopsy as a first-step surgical procedure, and more likely to have node dissection. PMID- 1420857 TI - Accuracy of death certificates: a population-based, complete-coverage, one-year autopsy study in East Germany. AB - The Goerlitz Autopsy Study is a population-based autopsy study, conducted in 1987 in the municipality of Goerlitz, population 78,484, in former East Germany. It is unique in that 1,023 (96.5 percent) of the 1,060 subjects who died in the municipality over a period of one year were investigated by full autopsy. An underlying cause was assigned to every death, using the procedures recommended by the International Classification of Diseases, Injuries and Causes of Death, ninth revision, German edition. Assignment of cause of death was done independently by the attending clinician and the pathology team who performed the autopsy. The data were analyzed through cross-classification of deaths by death certificate diagnosis and autopsy-based diagnosis. Sensitivity and positive predictive values were calculated for the death certificate diagnoses, assuming that the autopsy findings represent the correct reference set. Overall, 47 percent of diagnoses on death certificates differed from those based on autopsy and, for 30 percent of the subjects, the difference crossed a major disease category. The proportion of disagreement was higher for deaths occurring in nursing homes and among the very old, but was unrelated to gender. In the death certificates, diseases of the circulatory system and endocrine and metabolic disorders were over-represented, whereas infectious diseases, neoplasms, and respiratory, digestive, and genitourinary diseases were under-represented. Neoplasms in the death certificates are characterized by relatively high sensitivity and predictive values, even though these were still unsatisfactory, given the chronicity of the clinical course and the opportunities available for correct diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420858 TI - Oral contraceptive use and risk of cutaneous malignant melanoma. AB - The relation between cutaneous malignant melanoma (MM) and the use of oral contraceptives (OC) was investigated in a case-control study carried out from 1979 to 1991 among patients in hospitals and clinics in the Philadelphia (PA) and New York City (NY) metropolitan areas (United States). Cases were 615 women under age 70 who recently had been diagnosed with invasive melanoma; controls were 2,107 women of the same ages who had been treated for other conditions unrelated either to OC use or to skin diseases. The cases were categorized as severe or nonsevere based on the depth of invasion of the tumor or the presence or absence of metastases. Among the severe cases, OC use was not associated with MM: the relative risk (RR) estimate for ever-use was 1.1 (95 percent confidence interval [CI] = 0.8-1.5) and the estimate for 10 or more years of use was 1.1 (CI = 0.6 2.1). Nor was risk associated with recent use, long latency, or young age at first use. Among the nonsevere cases, ever-use of oral contraceptives was associated positively with MM (RR = 1.5, CI = 1.1-2.4) but there was no trend with increased duration of use. The findings provide evidence against the hypothesis that OC use increases the risk of malignant melanoma. The elevated estimates among the nonsevere cases most likely reflect selection bias rather than a causal relation. PMID- 1420860 TI - Childhood leukemia and neonatal exposure to lighting in nurseries. PMID- 1420859 TI - Occupational risk factors for multiple myeloma among Danish men. AB - A large population-based case-control study evaluated occupational exposures in 1,098 Danish males diagnosed with multiple myeloma from 1970 to 1984 and in 4,169 age- and gender-matched controls alive at the time of case-diagnosis. Industrial histories were obtained from the Supplementary Pension Fund which, since 1964, has recorded employments of adult Danes; occupation came from subjects' most recent tax records. Four industrial hygienists created a job-exposure matrix for 47 substances based on 15,000 unique industry/occupation combinations in subjects' histories. Risk of myeloma was significantly elevated among road and railroad workers, precision metalworkers, and workers in the transportation and communication industries. Risk increased significantly with duration of employment in: production of synthetic yarns, plastic packaging, and miscellaneous chemical compounds; fabricating structural metal and stationary tanks; body factories; electrical plants; and retail sale of paint and wallpaper. Risks of myeloma were elevated, though statistically nonsignificantly, in all categories of exposure to gasoline and engine exhausts. Risks rose with likelihood and duration of exposure to phthalates, and were statistically significant and nearly fivefold with probable exposure to vinyl chloride for five or more years. After adjusting for multiple exposures and disregarding exposures within 10 years of diagnosis (or selection as a control), probable exposure to vinyl chloride was associated with increased risk of myeloma, which rose to fivefold with longer exposure. Associations with gasoline, engine exhausts, and phthalates persisted, but were inconsistent with duration and probability of exposure. Previously reported associations with agriculture were not confirmed by these data. PMID- 1420861 TI - Computer modeling of fibrin polymerization kinetics correlated with electron microscope and turbidity observations: clot structure and assembly are kinetically controlled. AB - Although much is known about fibrin polymerization, because it is complex, the effects of various modifications are not intuitively obvious and many experimental observations remain unexplained. A kinetic model presented here that is based on information about mechanisms of assembly accounts for most experimental observations and allows hypotheses about the effects of various factors to be tested. Differential equations describing the kinetics of polymerization were written and then solved numerically. The results have been related to turbidity profiles and electron microscope observations. The concentrations of intermediates in fibrin polymerization, and fiber diameters, fiber and protofibril lengths have been calculated from these models. The simplest model considered has three steps; fibrinopeptide A cleavage, protofibril formation, and lateral aggregation of protofibrils to form fibers. The average number of protofibrils per fiber, which is directly related to turbidity, can be calculated and plotted as a function of time. The lag period observed in turbidity profiles cannot be accurately simulated by such a model, but can be simulated by modifying the model such that oligomers must reach a minimum length before they aggregate. Many observations, reported here and elsewhere, can be accounted for by this model; the basic model may be modified to account for other experimental observations. Modeling predicts effects of changes in the rate of fibrinopeptide cleavage consistent with electron microscope and turbidity observations. Changes only in the rate constants for initiation of fiber growth or for addition of protofibrils to fibers are sufficient to account for a wide variety of other observations, e.g., the effects of ionic strength or fibrinopeptide B removal or thrombospondin. The effects of lateral aggregation of fibers has also been modeled: such behavior has been observed in turbidity curves and electron micrographs of clots formed in the presence of platelet factor 4. Thus, many aspects of clot structure and factors that influence structure are directly related to the rates of these steps of polymerization, even though these effects are often not obvious. Thus, to a large extent, clot structure is kinetically determined. PMID- 1420862 TI - Brain stimulation using electromagnetic sources: theoretical aspects. AB - We prove that, at the frequencies generally proposed for extracranial stimulation of the brain, it is not possible, using any superposition of external current sources, to produce a three-dimensional local maximum of the electric field strength inside the brain. The maximum always occurs on a boundary where the conductivity jumps in value. Nevertheless, it may be possible to achieve greater two-dimensional focusing and shaping of the electric field than is currently available. Towards this goal we have used the reciprocity theorem to present a uniform treatment of the electric field inside a conducting medium produced by a variety of sources: an external magnetic dipole (current loop), an external electric dipole (linear antenna), and surface and depth electrodes. This formulation makes use of the lead fields from magneto- and electroencephalography. For the special case of a system with spherically symmetric conductivity, we derive a simple analytic formula for the electric field due to an external magnetic dipole. This formula is independent of the conductivity profile and therefore embraces spherical models with any number of shells. This explains the "insensitivity" to the skull's conductivity that has been described in numerical studies. We also present analytic formulas for the electric field due to an electric dipole, and also surface and depth electrodes, for the case of a sphere of constant conductivity. PMID- 1420863 TI - Gating of mammalian cardiac gap junction channels by transjunctional voltage. AB - Numerous two-cell voltage-clamp studies have concluded that the electrical conductance of mammalian cardiac gap junctions is not modulated by the transjunctional voltage (Vj) profile, although gap junction channels between low conductance pairs of neonatal rat ventricular myocytes are reported to exhibit Vj dependent behavior. In this study, the dependence of macroscopic gap junctional conductance (gj) on transjunctional voltage was quantitatively examined in paired 3-d neonatal hamster ventricular myocytes using the double whole-cell patch-clamp technique. Immunolocalization with a site-specific antiserum directed against amino acids 252-271 of rat connexin43, a 43-kD gap junction protein as predicted from its cDNA sequence, specifically stained zones of contact between cultured myocytes. Instantaneous current-voltage (Ij-Vj) relationships of neonatal hamster myocyte pairs were linear over the entire voltage range examined (0 less than or equal to Vj less than or equal to +/- 100 mV). However, the steady-state Ij-Vj relationship was nonlinear for Vj greater than +/- 50 mV. Both inactivation and recovery processes followed single exponential time courses (tau inactivation = 100-1,000 ms, tau recovery approximately equal to 300 ms). However, Ij recovered rapidly upon polarity reversal. The normalized steady-state junctional conductance-voltage relationship (Gss-Vj) was a bell-shaped curve that could be adequately described by a two-state Boltzmann equation with a minimum Gj of 0.32 0.34, a half-inactivation voltage of -69 and +61 mV and an effective valence of 2.4-2.8. Recordings of gap junction channel currents (ij) yielded linear ij-Vj relationships with slope conductances of approximately 20-30 and 45-50 pS. A kinetic model, based on the Boltzmann relationship and the polarity reversal data, suggests that the opening (alpha) and closing (beta) rate constants have nearly identical voltage sensitivities with a Vo of +/- 62 mV. The data presented in this study are not consistent with the contingent gating scheme (for two identical gates in series) proposed for other more Vj-dependent gap junctions and alternatively suggest that each gate responds to the applied Vj independently of the state (open or closed) of the other gate. PMID- 1420864 TI - A quasi-elastic light scattering study of smooth muscle myosin in the presence of ATP. AB - We have investigated the hydrodynamic properties of turkey gizzard smooth muscle myosin in solution using quasi-elastic light scattering (QELS). The effects of ionic strength (0.05-0.5 M KCl) and light chain phosphorylation on the conformational transition of myosin were examined in the presence of ATP at 20 degrees C. Cumulant analysis and light scattering models were used to describe the myosin system in solution. A nonlinear least squares fitting procedure was used to determine the model that best fits the data. The conformational transition of the myosin monomer from a folded form to an extended form was clearly demonstrated in a salt concentration range of 0.15-0.3 M KCl. Light chain phosphorylation regulates the transition and promotes unfolding of the myosin. These results agree with the findings obtained using sedimentation velocity and electron microscopy (Onishi and Wakabayashi, 1982; Trybus et al., 1982; Trybus and Lowey, 1984). In addition, we present evidence for polymeric myosin coexisting with the two monomeric myosin species over a salt concentration range from 0.05 to 0.5 M KCl. The size of the polymeric myosin varied with salt concentration. This observation supports the hypothesis that, in solution, a dynamic equilibrium exists between the two conformations of myosin monomer and filaments. PMID- 1420865 TI - Chain-length dependence of lipid bilayer properties near the liquid crystal to gel phase transition. AB - The temperature dependence of the mean orientational order parameter in the vicinity of the liquid crystal to gel phase transition is obtained from the first moment M1 of deuterium nuclear magnetic resonance spectra for bilayers of chain perdeuterated phosphatidylcholines with acyl chains of 12, 14, 16, and 18 carbons. The data clearly show an increasing temperature dependence of the orientational order parameter in the vicinity of the transition, with the effect becoming more pronounced with decreasing chain length. Assuming a linear relationship between the mean orientational order parameter and the extension of the acyl chain, estimates of the change in area of the membrane at the transition are shown to be consistent with those obtained from other measurements. It is shown that the transition may be modeled in terms of a Landau expansion of the free energy involving a small number of phenomenological parameters. From this it is shown that the behavior of these systems in the temperature range of interest is, in large part, controlled by the close proximity of a spinodal to the transition temperature. PMID- 1420866 TI - Resonance Raman spectroscopic and kinetic consequences of a nitrogen ... sulphur enzyme-substrate contact in a series of dithioacylpapains. AB - The resonance Raman (RR) spectroscopic, conformational, and kinetic properties of six dithioacylpapain intermediates have been examined. Five of the intermediates are of the form N-(methyloxycarbonyl)-X-glycine-C(= S)S-papain, where X is L phenyl-alanine, D-phenylalanine, glycine, L-phenylglycine, or D-phenylglycine. The sixth intermediate is N-phenylacetyl-glycine-C(= S)S-papain. Throughout the series there is an approximately 50-fold variation in kcat, the rate constant for deacylation, and a 1750-fold variation in kcat/KM. Existing RR spectra structure correlations allow us to define the torsional angles in the NH-CH2-C(= S)-S-CH2 CH fragment of the functioning intermediates. The values of these angles for each bound substrate appear to be very similar, with the substrates assuming a B-type conformer such that the nitrogen atom of the P1 glycine residue is cis to the thiol sulphur atom of cysteine-25. For each intermediate, the C(= S)S-CH2CH torsional angle is approximately -90 degrees, whereas for the SCH2-CH torisonal angle the cysteine-25 thiol sulphur (S) and cysteine-25 C alpha hydrogen (H) atoms are approximately trans. The three acyl-enzymes with the lowest catalytic rate constants, viz. N-(methyloxycarbonyl)-glycine-glycine-, N (methyloxycarbonyl)-L-phenylglycine-glycine-, or N-(phenylacetyl)-glycine dithioacylpapains, have atypical RR spectra in that they show a feature of medium intensity in the 1,085-cm-1 region. This band is sensitive to NH to ND exchange of the P1 glycine residues' (-NH-) function and, thus, the corresponding mode involves an excursion of the NH hydrogen. It is hypothesized that the high intensity is due to a particularly strong interaction between the P1 glycine nitrogen atom and the thiol sulphur of cysteine-25, which also has the effect of retarding deacylation, because the nitrogen . . . sulphur contact has to be broken in the rate-determining step. PMID- 1420867 TI - Pulmonary surfactant protein SP-C causes packing rearrangements of dipalmitoylphosphatidylcholine in spread monolayers. AB - The hydrophobic pulmonary surfactant protein SP-C has been isolated from porcine lung surfactant, and it has been incorporated into monolayers of dipalmitoylphosphatidylcholine (DPPC). The monolayers, which contained 1 mol% of a fluorescently-labeled phosphatidylcholine, were observed under various states of compression in an epifluorescence surface balance. SP-C altered the packing arrangements of DPPC in the monolayer, causing the production of many more, smaller condensed lipid domains in its presence than in its absence. PMID- 1420868 TI - Monomer diffusion and polymer alignment in domains of sickle hemoglobin. AB - We have used polarized absorbance to observe the process of monomer accretion and polymer alignment which occurs in domains of sickle hemoglobin that are formed and maintained by laser photolysis. These diffusion and alignment processes have been studied as a function of initial concentration and temperature (initial and final), as well as beam size and domain number. Monomers are found to diffuse into growing polymer domains with a rate that is essentially temperature and concentration independent, but which depends on the size of the final domain boundaries, and the number of domains within a boundary. The final concentrations achieved are very close to those found in packed centrifugation experiments (50 55 g/dl) and are approximately independent of starting temperature and concentration. The influx of monomers is accompanied by polymer alignment, and the amount aligned is proportional to the amount diffused throughout the process. We propose that polymer alignment controls the influx of added monomers into the growing domain. PMID- 1420869 TI - Binding kinetics of an anti-dinitrophenyl monoclonal Fab on supported phospholipid monolayers measured by total internal reflection with fluorescence photobleaching recovery. AB - Fluorescence photobleaching recovery with total internal reflection illumination (TIR-FPR) has been used to measure the dissociation kinetics of a fluorescein labeled anti-dinitrophenyl monoclonal Fab specifically bound to supported monolayers composed of a mixture of dipalmitoylphosphatidylcholine and dinitrophenyl-conjugated dipalmitoylphosphatidylethanolamine. The fluorescence recovery curves were not monoexponential; when analyzed as a sum of two exponentials, the rates and fractional recoveries were approximately 1 s-1 (approximately 50%) and approximately 0.1 s-1 (approximately 30%). The data did not change as a function of the Fab solution concentration, indicating that the fluorescence recovery curves were not influenced by the rate of diffusion in bulk solution. Also, the recovery curves were independent of the size of the illuminated area, indicating that surface diffusion did not significantly contribute to the rate and shape of the fluorescence recovery. The measured off rates and apparent association constant (1.6 x 10(5) M-1) were analyzed with the theoretical formalism for a proposed mechanism that accounts for the nonmonoexponential kinetics. PMID- 1420870 TI - A membrane model for cytosolic calcium oscillations. A study using Xenopus oocytes. AB - Cytosolic calcium oscillations occur in a wide variety of cells and are involved in different cellular functions. We describe these calcium oscillations by a mathematical model based on the putative electrophysiological properties of the endoplasmic reticulum (ER) membrane. The salient features of our membrane model are calcium-dependent calcium channels and calcium pumps in the ER membrane, constant entry of calcium into the cytosol, calcium dependent removal from the cytosol, and buffering by cytoplasmic calcium binding proteins. Numerical integration of the model allows us to study the fluctuations in the cytosolic calcium concentration, the ER membrane potential, and the concentration of free calcium binding sites on a calcium binding protein. The model demonstrates the physiological features necessary for calcium oscillations and suggests that the level of calcium flux into the cytosol controls the frequency and amplitude of oscillations. The model also suggests that the level of buffering affects the frequency and amplitude of the oscillations. The model is supported by experiments indirectly measuring cytosolic calcium by calcium-induced chloride currents in Xenopus oocytes as well as cytosolic calcium oscillations observed in other preparations. PMID- 1420871 TI - Simulations of the temperature dependence of energy transfer in the PSI core antenna. AB - In order to understand the organization of the PSI core antenna and to interpret results obtained from studies of the temperature and wavelength dependence of energy transfer and trapping in the PSI particles, we have constructed a model for PSI in which spectral heterogeneity is considered via a self-consistent approach based on Forster transport. The temperature dependence of the absorption and emission spectra of the individual Chl molecules in the protein matrix is calculated based on a model Hamiltonian which includes a phonon contribution. Time and wavelength resolved kinetics of PSI at different temperatures are investigated by means of two-dimensional lattice models. We conclude that wavelength-dependent fluorescence decay kinetics result only when two or more bottlenecks exist in the energy transfer and trapping process. A single trap or several pseudo-traps with spectrally identical environments do not lead to wavelength dependent decays. Simple funnel arrangements of the spectral types can be ruled out. At least one pigment with energy lower than the photochemical trap located close to the reaction center is required to produce the trends of the fluorescence lifetimes observed experimentally. The remainder of the core antenna is consistent with a random arrangement of spectral types. PMID- 1420872 TI - Study of mechanisms of electric field-induced DNA transfection. III. Electric parameters and other conditions for effective transfection. AB - Electric parameters, osmolality, temperature, and pH of the suspending medium and the growth phase of cells, etc., are known to influence the efficiency of the pulsed electric field (PEF)-induced DNA transfection of cells. PEF-induced transfection of Escherichia coli JM105 by plasmid DNA PUC18, PUC19, PBR322, and PMSG has been used as a model system to establish quantitative relationships between these parameters and transfection efficiency. The main findings are summarized for experiments using unipolar square wave PEF. (a) For a given field strength (up to 6 kV/cm), the transfection efficiency (TE) was linearly dependent on the pulse width (up to 1 ms). (b) When field strength is fixed, Log [TE] correlated with the number of pulses applied. Similarly, when field duration was fixed, Log [TE] correlated with the number of pulses. (c) In the absence of MgCl2, TE showed a maximal value at 50 mM sucrose and was reduced by several fold at lower and higher sucrose concentrations. Cell survival was nearly constant in the range 1-300 mM sucrose. (d) E. coli in the early and mid-exponential growth phases was more susceptible to PEF for DNA transfection than it was in the stationary phase. (e) For a given set of electric parameters, TE was the highest at neutral pH and was greatly reduced at acidic and alkaline pH. (f) Increasing the temperature from 0 to 37 degrees C resulted in the reduction of TE by three orders of magnitude. This could reflect a rapid shrinking of pores at higher temperatures. (g) TE was inversely proportional to the square of the size of the plasmid DNA. By adjusting the above parameters to optimize transfection, a TE of 1010 1microg-1 DNA (PUC18) has been recorded. Further improvement in percent cell transfection may be expected by a more exhaustive search of conditions than the present study has done. PMID- 1420873 TI - Folding kinetics of designer proteins. Application of the diffusion-collision model to a de novo designed four-helix bundle. AB - A folding algorithm is described, based on the diffusion-collision model, combining static and dynamic calculational methods. The algorithm is applied to predict the basic structure and schematic folding pathways of an artificial four helix bundle. PMID- 1420874 TI - Effect of small release on force during sarcomere-isometric tetani in frog muscle fibers. AB - We investigated the effect of small shortening imposed on frog muscle fibers during sarcomere-isometric tetani. Sarcomere length was initially kept constant, then slightly shortened (1%-5% of initial length) and clamped again for the remainder of the tetanus. Force level after the shortening was higher than the force level preceding the release. The size of the increase was larger than that predicted by the descending limb of the linear force-length relation. The difference between measured and predicted force levels increased with sarcomere length. At a sarcomere length of 3.2 microns, the force level after the shortening was higher by 50% than the force level expected from the linear descending limb. Dispersion of sarcomere-length within the sampled region was measured by two independent methods: striation imaging and analysis of the intensity profile of the first diffraction order. Sarcomere-length inhomogeneity in the sampled region was too small (standard deviation from the average sarcomere-length was +/- 0.03 microns) to account for the size of the increase in force. We studied the dependence of increase in tetanic force level after small sarcomere-length release on the size, velocity and timing of the release, as well as on initial sarcomere-length. Release size was the major determinant of the amount of increase in force. Release of 20 nm per half sarcomere was sufficient to produce an almost full force increase. Larger releases increased the force only moderately. Over the range studied, release velocity and timing had little or no effect. PMID- 1420875 TI - Transport methods for probing the barrier domain of lipid bilayer membranes. AB - Two experimental techniques have been utilized to explore the barrier properties of lecithin/decane bilayer membranes with the aim of determining the contributions of various domains within the bilayer to the overall barrier. The thickness of lecithin/decane bilayers was systematically varied by modulating the chemical potential of decane in the annulus surrounding the bilayer using different mole fractions of squalene in decane. The dependence of permeability of a model permeant (acetamide) on the thickness of the solvent-filled region of the bilayer was assessed in these bilayers to determine the contribution of this region to the overall barrier. The flux of acetamide was found to vary linearly with bilayer area with Pm = (2.9 +/- 0.3) x 10(-4) cm s-1, after correcting for diffusion through unstirred water layers. The ratio between the overall membrane permeability coefficient and that calculated for diffusion through the hydrocarbon core in membranes having maximum thickness was 0.24, suggesting that the solvent domain contributes only slightly to the overall barrier properties. Consistent with these results, the permeability of acetamide was found to be independent of bilayer thickness. The relative contributions of the bilayer interface and ordered hydrocarbon regions to the transport barrier may be evaluated qualitatively by exploring the effective chemical nature of the barrier microenvironment. This may be probed by comparing functional group contributions to transport with those obtained for partitioning between water and various model bulk solvents ranging in polarity or hydrogen-bonding potential. A novel approach is described for obtaining group contributions to transport using ionizable permeants and pH adjustment. Using this approach, bilayer permeability coefficients of p-toluic acid and p-hydroxymethyl benzoic acid were determined to be 1.1 +/- 0.2 cm s-1 and (1.6 +/- 0.4) x 10(-3) cm s-1, respectively. From these values, the -OH group contribution to bilayer transport [delta(delta G0-OH)] was found to be 3.9 kcal/mol. This result suggests that the barrier region of the bilayer does not resemble the hydrogen-bonding environment found in octanol, but is somewhat less selective (more polar) than a hydrocarbon solvent. PMID- 1420876 TI - Indo-1 binding to protein in permeabilized ventricular myocytes alters its spectral and Ca binding properties. AB - We have examined the binding of the fluorescent Ca indicator indo-1 to cellular protein in permeabilized ventricular myocytes and also to soluble and particulate myocyte protein. Using either a filtration technique or equilibrium dialysis, and conditions similar to those in a cardiac myocyte patch clamped with 100 microM indo-1 in the patch pipette, we found that 72% of the total indo-1 was bound to myocyte protein at a protein concentration of 100 mg/ml. This corresponds to a binding of 3.8 +/- 0.5 nmol indo-1/mg protein. Separation of the myocyte protein into a soluble and a particulate fraction showed that 63% of the bound indo-1 was bound to soluble protein, corresponding to a binding of 3.22 +/- 0.99 nmol/mg, whereas 37% of the bound indo-1 was bound to particulate protein (0.85 +/- 0.14 nmol/mg) at a low [Ca] (pCa approximately 9). Binding of indo-1 in permeabilized myocytes was approximately 60% higher at a saturating Ca concentration (pCa = 3), than under Ca free conditions (1 mM EGTA). Simultaneous measurements of free [Ca] with a Ca selective electrode and indo-1 fluorescence showed that, the dissociation constant (Kd) for Ca was increased 4-5 fold in the presence of permeabilized myocytes as compared to the value obtained in vitro. In agreement with the binding experiments we estimate that the true Kd and the apparent Kd (using ratiometric measurements) for Ca binding to indo-1 are increased approximately four fold, at a myocyte protein concentration of 100 mg/ml. PMID- 1420877 TI - Implications of epidermal growth factor (EGF) induced egf receptor aggregation. AB - To investigate the role of receptor aggregation in EGF binding, we construct a mathematical model describing receptor dimerization (and higher levels of aggregation) that permits an analysis of the influence of receptor aggregation on ligand binding. We answer two questions: (a) Can Scatchard plots of EGF binding data be analyzed productively in terms of two noninteracting receptor populations with different affinities if EGF induced receptor aggregation occurs? No. If two affinities characterize aggregated and monomeric EGF receptors, we show that the Scatchard plot should have curvature characteristic of positively cooperative binding, the opposite of that observed. Thus, the interpretation that the high affinity population represents aggregated receptors and the low affinity population nonaggregated receptors is wrong. If the two populations are interpreted without reference to receptor aggregation, an important determinant of Scatchard plot shape is ignored. (b) Can a model for EGF receptor aggregation and EGF binding be consistent with the "negative curvature" (i.e., curvature characteristic of negatively cooperative binding) observed in most Scatchard plots of EGF binding data? Yes. In addition, the restrictions on the model parameters required to obtain negatively curved Scatchard plots provide new information about binding and aggregation. In particular, EGF binding to aggregated receptors must be negatively cooperative, i.e., binding to a receptor in a dimer (or higher oligomer) having one receptor already bound occurs with lower affinity than the initial binding event. A third question we consider is whether the model we present can be used to detect the presence of mechanisms other than receptor aggregation that are contributing to Scatchard plot curvature. For the membrane and cell binding data we analyzed, the best least squares fits of the model to each of the four data sets deviate systematically from the data, indicating that additional factors are also important in shaping the binding curves. Because we have controlled experimentally for many sources of receptor heterogeneity, we have limited the potential explanations for residual Scatchard plot curvature. PMID- 1420878 TI - Atomic force microscopy of three-dimensional membrane protein crystals. Ca-ATPase of sarcoplasmic reticulum. AB - We have observed three-dimensional crystals of the calcium pump from sarcoplasmic reticulum by atomic force microscopy (AFM). From AFM images of dried crystals, both on graphite and mica, we measured steps in the crystal thickness, corresponding to the unit cell spacing normal to the substrate. It is known from transmission electron microscopy that crystal periodicity in the plane of the substrate is destroyed by drying, and it was therefore not surprising that we were unable to observe this periodicity by AFM. Thus, we were motivated to use the AFM on hydrated crystals. In this case, crystal adsorption appeared to be a limiting factor, and our studies indicate that adsorption is controlled by the composition of the medium and by the physical-chemical properties of the substrate. We used scanning electron microscopy to determine the conditions yielding the highest adsorption of crystals, and, under these conditions, we have obtained AFM images of hydrated crystals with a resolution similar to that observed with dried samples (i.e., relatively poor). In the same preparations, we have observed lipid bilayers with a significantly better resolution, indicating that the poor quality of crystal images was not due to instrumental limitations. Rather, we attribute poor images to the intrinsic flexibility of these multilamellar crystals, which apparently allow movement of one layer relative to another in response to shear forces from the AFM tip. We therefore suggest some general guidelines for future studies of membrane proteins with AFM. PMID- 1420879 TI - Nonmonotonic alterations in the fluorescence anisotropy of polar head group labeled fluorophores during the lamellar to hexagonal phase transition of phospholipids. AB - The temperature dependence of the fluorescence anisotropy of polar head group labeled fluorophores (i.e., N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)dipalmitoyl-L- alpha-phosphatidylethanolamine or N-(lissamine rhodamine B sulfonyl)dipalmitoyl-L alpha-phosphatidylethanol- amine) incorporated into multiple phosphatidylethanolamine molecular species was parabolic, possessing minima (dr/dT = 0) that precisely correlated with the respective lamellar (L alpha) to hexagonal (HII) phase transition temperature of each species. The parabolic alterations in the thermotropic behavior of these fluorophores were due to increased motional constraints in the polar head group region during heating (dr/dT greater than 0), because significant alterations in the fluorescence lifetimes of these probes during the phase transition did not occur. The sensitivity inherent in identification of peak minima was exploited to determine the lamellar to hexagonal phase transition temperatures of several homogeneous molecular species of plasmenylethanolamine (e.g., the transition temperature of 1 O-(Z)-hexadec-1'-enyl-2-octadec-9'- enoyl-sn-glycero-3-phosphoethanolamine was 28 degrees C). Experiments using ethanolamine glycerophospholipids containing either an ester or a vinyl ether linkage at the sn-1 position demonstrated that introduction of the vinyl ether constituent increased the propensity of these species to assume the hexagonal phase. Collectively, these results identify and substantiate a new technique for the characterization of the lamellar to hexagonal phase transition in phospholipids that requires only small amounts of phospholipids present in dilute membrane suspensions. PMID- 1420880 TI - Optical and physical properties of wet-spun films of Na-hyaluronate. Evidence of a phase transition. AB - The refractive indices, water content, and volume of wet-spun films of Na hyaluronate have been measured as a function of relative humidity (rh). These data are used with the Lorentz-Lorenz formula to determine the optical polarizabilities of Na-hyaluronate parallel and perpendicular to the helical axis. The analysis reveals a drop in the optical polarizabilities of approximately 20% between 80 and 88% rh, indicating a phase transition. PMID- 1420881 TI - Formation of a new stable phase of phosphatidylglycerols. AB - Dilauroyl and dimyristoylphosphatidylglycerol (DMPG) form a more stable gel state when aqueous suspensions are incubated several days at low temperature (0-2 degrees C), pH 7.4 with 0.15 M NaCl. This gel state is characterized by a higher transition temperature and a higher transition enthalpy. The geometry of this gel state is distinguishable from the metastable gel state that forms rapidly upon hydration on the basis of its x-ray diffraction pattern. Infrared spectra in the CH2 scissoring region indicate that the stable gel phase of DMPG is also characterized by reduced reorientational fluctuations of acyl chains and increased interchain interactions. Analysis of vibrational bands due to ester carbonyl groups of DMPG suggests that the transition to a new gel phase is initiated by changes in the interfacial and/or headgroup region of the bilayer, most likely via formation of interlipid hydrogen bonds. The melting of the stable gel phase of DMPG is accompanied by a gross morphological change resulting in vesiculation. PMID- 1420882 TI - Techniques for obtaining analytical solutions to the multicylinder somatic shunt cable model for passive neurones. AB - The somatic shunt cable model for neurones is extended to the case in which several equivalent cylinders, not necessarily of the same electrotonic length, emanate from the cell soma. The cable equation is assumed to hold in each cylinder and is solved with sealed end conditions and a lumped soma boundary condition at a common origin. A Green's function (G) is defined, corresponding to the voltage response to an instantaneous current pulse at an arbitrary point along one of the cylinders. An eigenfunction expansion for G is obtained where the coefficients are determined using the calculus of residues and compared with an alternative method of derivation using a modified orthogonality condition. This expansion converges quickly for large time, but, for small time, a more convenient alternative expansion is obtained by Laplace transforms. The voltage response to arbitrary currents injected at arbitrary sites in the dendritic tree (including the soma) may then be expressed as a convolution integral involving G. Illustrative examples are presented for a point charge input. PMID- 1420883 TI - Long tail kinetics in biophysics? AB - Long tail kinetics describe a variety of data from complex, disordered materials that cannot be described by conventional kinetics. It is suggested that the kinetics of diffusive motion in complex biological media, such as cytoplasm or biomembranes, might also have long tails. The effects of long tail kinetics are investigated for two standard biophysical measurements, fluorescence recovery after photobleaching (FRAP), and dynamic light scattering (DLS). It is shown that long tail kinetic data would yield significantly distorted and misleading results when analyzed assuming conventional kinetics. PMID- 1420884 TI - Analysis of electric field stimulation of single cardiac muscle cells. AB - Electrical stimulation of cardiac cells by imposed extracellular electric fields results in a transmembrane potential which is highly nonuniform, with one end of the cell depolarized and the other end hyperpolarized along the field direction. To date, the implications of the close proximity of oppositely polarized membranes on excitability have not been explored. In this work we compare the biophysical basis for field stimulation of cells at rest with that for intracellular current injection, using three Luo-Rudy type membrane patches coupled together as a lumped model to represent the cell membrane. Our model shows that cell excitation is a function of the temporal and spatial distribution of ionic currents and transmembrane potential. The extracellular and intracellular forms of stimulation were compared in greater detail for monophasic and symmetric biphasic rectangular pulses, with duration ranging from 0.5 to 10 ms. Strength-duration curves derived for field stimulation show that over a wide range of pulse durations, biphasic waveforms can recruit and activate membrane patches about as effectively as can monophasic waveforms having the same total pulse duration. We find that excitation with biphasic stimulation results from a synergistic, temporal summation of inward currents through the sodium channel in membrane patches at opposite ends of the cell. Furthermore, with both waveform types, a net inward current through the inwardly rectifying potassium channel contributes to initial membrane depolarization. In contrast, models of stimulation by intracellular current injection do not account for the nonuniformity of transmembrane potential and produce substantially different (even contradictory) results for the case of stimulation from rest. PMID- 1420886 TI - Virtual intermediates in photosynthetic electron transfer. AB - We explore the possibility of virtual transfer in the primary charge separation of photosynthetic bacteria within the context of several types of experimental data. We show that the peak that might be expected in the virtual rate as electric fields vary the intermediate state energy is severely broadened by coupling to high-frequency modes. The Stark absorption kinetics data are thus consistent with virtual transfer in the primary charge separation. High-frequency coupling also makes the temperature dependence weak over a wide range of parameters. We demonstrate that Stark fluorescence anisotropy data, usually taken as evidence of virtual transfer, can in fact be consistent with two-step transfer. We suggest a two-pulse excitation experiment to quantify the contributions from two-step and virtual transfer. We show that virtual absorption into a charge transfer state can make a substantial contribution to the Stark absorption spectrum in a way that is not related to any derivative of the absorption spectrum. PMID- 1420885 TI - Evidence for structurally different attached states of myosin cross-bridges on actin during contraction of fish muscle. AB - Using data from fast time-resolved x-ray diffraction experiments on the synchrotrons at Daresbury and (Deutsches Elektronen Synchrotron [DESY]), it is shown that during contraction of fish muscle there are at least two distinct configurations of myosin cross-bridges on actin, that they appear to have different tension producing properties and that they probably differ in the axial tilt of the cross-bridges on actin. Evidence is presented for newly observed myosin-based layer lines in patterns from active fish muscle, together with intensity changes of the actin layer lines. On the equator, the 110 reflection changes much faster (time for 50% change t1/2 = 21 +/- 4 ms after activation) than the 100 reflection (t1/2 = 35 +/- 8 ms) and tension (t1/2 = 41 +/- 3 ms) during the rising phase of tetanic contractions. These and higher order reflections have been used to show the time course of mass attachment at actin during this rising phase. Mass arrival (t1/2 = 25 ms) precedes tension by approximately 15 ms. Analysis has been carried out to evaluate the effects of changes in sarcomere length during the tetanus. It is shown that any such effects are very small. Difference "equatorial" electron density maps between active muscle at a time when mass arrival at actin is just complete, but the tension is still rising, and at a later time well into the tension plateau, show that the structural difference between the lower and higher force states corresponds to mass movement consistent with axial swinging of heads from a nonstereospecific actin attached state (low force) to a more stereospecific (high force) state. PMID- 1420887 TI - Formation of a square-planar Co(I) B12 intermediate. Implications for enzyme catalysis. AB - X-ray edge and extended x-ray absorption fine structure (EXAFS) techniques provide powerful tools for analysis of local molecular structure of complexes in solution. We present EXAFS results for Co(I) B12 that demonstrate a four coordinate (distorted) square-planar configuration. Comparison of EXAFS solutions for Co(I) and Co(II) B12 (collected previously; Sagi et al. 1990. J. Am. Chem. Soc. 112:8639-8644) suggest that modulation of the Co-N bond to the axial 5,6 dimethylbenzimidazole (DMB), in the absence of changes in Co-N (equatorial) bond distances, may be a key mechanism in promoting homolytic versus heterolytic cleavage. As Co-C bond homolysis occurs, the Co-N (DMB) bond becomes stronger. However, for heterolytic cleavage to occur, earlier electrochemical studies (D. Lexa and J. M. Saveant. 1976. J. Am. Chem. Soc. 98:2652-2658) and recent studies of methylcobalamin-dependent Clostridium thermoaceticum (Ragsdale et al. 1987. J. Biol. Chem. 262:14289-14297) suggest that removal of the DMB ligand (before Co-C bond cleavage) favors formation of the four-coordinate square-planar Co(I) species while inhibiting formation of the five-coordinate Co(II) B12 complex. This paper presents the first direct evidence that formation of the Co(I) B12 intermediate must involve breaking of the Co-N (DMB) bond. PMID- 1420888 TI - Influence of the membrane surface on glycolipid conformation and dynamics. An interpretation of NMR results using conformational energy calculations. AB - Glycolipids constitute an important class of biomolecules that are involved in biomolecular recognition. The importance of carbohydrate head group conformation in such processes is well recognized. Glycolipids typically occur as minor components of the complex heterogeneous matrix of a biological membrane. As a result, the membrane surface may not only influence head group conformation but also serves as a spatial frame in which the glycolipid is oriented and recognized. In this study, conformational energy calculations have been used to assess the conformational space available to the glucose head group of 1,2-di-O tetradecyl-3-O-(beta-D-glucopyranosyl)-sn-glycerol (beta-DTGL) in a liquid crystalline membrane matrix. 2H NMR quadrupolar splittings are calculated and compared with those observed experimentally. This study demonstrates the importance of including surface interactions when considering the conformational space accessible to cell surface carbohydrates. The empirical approach taken here provides considerable insight at the molecular level, and offers the possibility of exploring even more complex systems. PMID- 1420889 TI - Direct correlation of structure changes and thermal events in hydrated lipid established by simultaneous calorimetry and time-resolved x-ray diffraction. AB - In many lipid systems, polymorphic and mesomorphic behavior depends on sample thermal history. To establish unequivocally the structural origin of endothermic and exothermic events in such systems, we have performed simultaneous calorimetry and time-resolved x-ray diffraction (SCALTRD). To this end, aluminum calorimetry crucibles were used to contain the hydrated lipid sample, and the calorimeter was mounted with the base of the crucible oriented perpendicular to a synchrotron derived focused monochromatic x-ray beam for SCALTRD data collection. Measurements were made with hydrated monoelaidin and 1,2-dielaidoyl-sn-glycero-3 phosphoethanolamine (DEPE) contained in hermetically sealed crucibles. Time resolved x-ray diffraction (TRXRD) data were collected using an x-ray image intensifier/video system and a streak camera containing an x-ray sensitive image plate and/or film. SCALTRD analysis of the lamellar gel to lamellar liquid crystalline phase transition in hydrated monoelaidin gives identical progress curves by calorimetry and TRXRD at a scan rate of 1 degree C/min. At faster rates, calorimetry shows a broader phase transition that starts at a lower and ends at a higher temperature than is observed by TRXRD. The disparity arises in part because the x-ray beam used in TRXRD interrogates only a small portion of the sample, whereas the calorimeter responds to the entire sample volume. Because data collection times are relatively long, radiation damage is an important potential problem for SCALTRD measurements. Such an effect was observed with DEPE/water in that TRXRD shows the lamellar gel to lamellar liquid crystalline phase transition occurring at a lower temperature than observed by calorimetry. We speculate that the sample accumulates impurities locally as a result of radiation damage that has the effect of lowering the phase transition temperature at the site of interrogation by the x-ray beam. This "methods-in-combination" SCALTRD approach facilitates the direct correlation of structure rearrangements and thermal events in the same sample under identical conditions of thermal history. The information content of the data so derived far surpasses that available from either method used in isolation. PMID- 1420890 TI - Intermediates and kinetics of membrane fusion. AB - Recently, it has become clear that the influenza virus fusion protein, hemagglutinin (HA), produces membrane destabilization and fusion by a multistep process, which involves the aggregation of the HAs to form a fusion site. While the details of this process are under debate, it is important to recognize that proposing any sequence of "microscopic" fusion intermediates encumbers general "macroscopic" kinetic consequences, i.e., with respect to membrane mixing rates. Using a kinetic scheme which incorporates the essential elements of several recently proposed models, some of these measurable properties have been elucidated. First, a rigorous mathematical relationship between fusion intermediates and the fusion event itself is defined. Second, it is shown that what is measured as the macroscopic "fusion rate constant" is a simple function of all of the rate constants governing the transitions between intermediates, whether or not one of the microscopic steps is rate limiting. Third, while this kinetic scheme predicts a delay (or lag) time for fusion, as has been observed, it will be very difficult to extract reliable microscopic information from these data. Furthermore, it is predicted that the delay time can depend upon HA surface density even when the HA aggregation step is very rapid compared with fusion, i.e., the delay time need not be due to HA aggregation. Fourth, the inactivation process observed for influenza virions at low pH can be described within this kinetic scheme simply, yet rigorously, via the loss of the fusion intermediates. Fifth, predicted Arrhenius plots of fusion rates can be linear for this multistep scheme, even though there is no single rate-determining step and even when a branched step is introduced, i.e., where one pathway predominates at low temperature and the other pathway predominates at high temperature. Furthermore, the apparent activation energies obtained from these plots bear little or no quantitative resemblance to the microscopic activation energies used to simulate the data. Overall, these results clearly show that the intermediates of protein mediated fusion can be studied only by using assays sensitive to the formation of each proposed intermediate. PMID- 1420891 TI - Myosin light chain 2 modulates calcium-sensitive cross-bridge transitions in vertebrate skeletal muscle. AB - We investigated the mechanism of the Ca2+ sensitivity of cross-bridge transitions that limit the rate of force development in vertebrate skeletal muscle. The rate of force development increases with Ca2+ concentration in the physiological range. We show here that at low concentrations of Ca2+ the rate of force development increases after partial extraction of the 20-kD light chain 2 subunit of myosin, whereas reconstitution with light chain 2 fully restores native sensitivity to Ca2+ in skinned single skeletal fibers. Furthermore, elevated free Mg2+ concentration reduces Ca2+ sensitivity, an effect that is reversed by extraction of the light chain but not by disruption of thin-filament activation by partial removal of troponin C, the Ca2+ binding protein of the thin filament. Our findings indicate that the Ca2+ sensitivity of the rate of force development in vertebrate skeletal muscle is mediated in part by the light chain 2 subunit of the myosin cross-bridge. PMID- 1420892 TI - Melittin-induced changes in lipid multilayers. A solid-state NMR study. AB - Solid-state 1H, 13C, 14N, and 31P NMR spectroscopy was used to study the effects of the bee venom peptide, melittin, on aligned multilayers of dimyristoyl-, dilauryl- and ditetradecyl-phosphatidylcholines above the gel to liquid crystalline transition temperature, Tc. Both 31P spectra from the lipid headgroups and 1H resonances from the lipid acyl chain methylene groups indicate that the peptide does not affect the mosaic spread of the lipid molecules at lipid:peptide molar ratios of 10:1, or higher. None of the samples prepared above Tc showed any evidence of the formation of hexagonal or isotropic phases. Melittin-induced changes in the chemical shift anisotropy of the headgroup phosphate and the lipid carbonyl groups, and in the choline 14N quadrupole splittings, show that the peptide has effects on the headgroup order and on the molecular organization in the sections of the acyl chains nearest to the bilayer surface. The spin-lattice relaxation time for the lipid acyl chain methylene protons was found to increase and the rotating-frame longitudinal relaxation time to markedly decrease with the addition of melittin, suggesting that motions on the nanosecond time scale are restricted, whereas the slower, collective motions are enhanced in the presence of the peptide. PMID- 1420893 TI - Protein dynamics. Vibrational coupling, spectral broadening mechanisms, and anharmonicity effects in carbonmonoxy heme proteins studied by the temperature dependence of the Soret band lineshape. AB - In this work we study the temperature dependence of the Soret band lineshape of the carbonmonoxy derivatives of sperm whale myoglobin, human hemoglobin, and its isolated alpha and beta subunits. To fit the observed spectral profile we use an analytic expression derived for a system whereby a single electronic transition is coupled to Franck-Condon active vibrational modes, within the adiabatic and harmonic approximation. The vibronic structure of the spectra arises from the coupling with high frequency modes; these modes contribute to the total line shape through a series of Lorentzians with peak positions at vibrational overtones and half width related to the time constant of the population decay of the excited electronic state (homogeneous broadening); moreover, the coupling with low frequency modes broadens each Lorentzian to a Voigtian. Inhomogeneous broadening is modeled as a gaussian distribution of the 0-0 transition frequencies and is therefore added as a constant term to the previous gaussian width. This spectral deconvolution enables us to investigate the different contributions to line broadening and the parameters that characterize the vibrational coupling, as well as their dependence upon protein and solvent composition. The investigation is carried out as a function of temperature in the range 20-300 K; relevant information is obtained by comparing experimental results with theoretical predictions. This work supports a description of the investigated proteins as heterogeneous systems, whose heterogeneity depends on the particular protein and on the composition of the external matrix. The delocalized pi electron cloud of the porphyrin ring is coupled not only to the high frequency vibrational modes of the active site but also to a "bath" of lower frequency modes that involve the entire protein; moreover at suitable temperatures (approximately 200 K), anharmonic motions, which are an obvious prerequisite for the jumping among different conformational substates, become evident. PMID- 1420894 TI - Spatial variations in membrane properties in the intact rat lens. AB - We have used linear frequency domain techniques to measure impedance at various locations and depths in the intact rat lens. The data are used to obtain best-fit solutions to a new electrical model based on lens structure, allowing us to estimate localized conductances of surface cell membranes (Gs), fiber cell membranes (gm), and gap junctions (Gj) as functions of position. We find that gm is small and fairly uniform throughout the lens (2.02 +/- 0.58 microS/cm2); for the anterior surface-epithelial cells Gs = 1.26 +/- 0.19 mS/cm2; for the posterior surface differentiating fiber cells Gs = 0.46 +/- 0.04 mS/cm2. Thus, Gs varies about the equator in a stepwise fashion. Gj between fiber cells at locations interior to 80% of the radius is fairly uniform (0.75 S/cm2); but in the outer 20% Gj varies smoothly and symmetrically from both poles (0.66 S/cm2) to equator (5.95 S/cm2). This pattern of variation in Gj is similar to the pattern of inward and outward currents reported by Robinson and Patterson (1983. Curr. Eye Res. 2:843-847). We therefore suggest that the nonuniform distribution of functional gap junctions, not the surface cell conductance or Na/K pumps, may be responsible for directing these current flows. Gap junctional uncoupling during exposure to elevated calcium and acidification was also examined. High calcium (20 mM, with the calcium ionophore A23187) produced modest (twofold) irreversible uncoupling along with large, irreversible decreases in membrane potential. We did not pursue this further. Acidification with 20 and 100% CO2 bubbled Tyrode's produced 5- and 15-fold reversible uncoupling, respectively, only in the outer 20% of the lens radius. The remaining inner 80% of the lens gap junctions seemed resistant to the acidification and did not uncouple. PMID- 1420895 TI - 1H nuclear magnetic resonance investigation of cobalt(II) substituted carbonic anhydrase. AB - The structure of ClO4 and NO3 adducts of cobalt(II) substituted bovine carbonic anhydrase have been investigated through 1D NOE and 2D 1H nuclear magnetic resonance (NMR) spectroscopy. For the first time two-dimensional NMR techniques are applied to paramagnetic metalloproteins other than iron-containing proteins. Several active site signals have been assigned to specific protons on the grounds of their scalar and dipolar connectivities and T1 values. The experimental dipolar shifts for the protons belonging to noncoordinated residues have allowed the identification of a plausible orientation of the magnetic susceptibility tensor around the cobalt ion as well as of the magnitude and the anisotropy of the principal susceptibility values. In turn, a few more signals have been tentatively assigned on the grounds of their predicted dipolar shifts. The two inhibitor derivatives have a very similar orientation but a different magnitude of the chi tensor, and the protein structure around the active site is highly maintained. The results encourage a more extensive use of the two-dimensional techniques for obtaining selective structural information on the active site of metalloenzymes. With this information at hand, comparisons within homologous series of adducts with various inhibitors and/or mutants of the same enzyme of known structure should be possible using limited sets of NMR data. PMID- 1420896 TI - Hydrogen peroxide plays a key role in the oxidation reaction of myoglobin by molecular oxygen. A computer simulation. AB - The stability properties of the iron(II)-dioxygen bond in myoglobin and hemoglobin are of particular importance, because both proteins are oxidized easily to the ferric met-form, which cannot be oxygenated and is therefore physiologically inactive. In this paper, we have formulated all the possible pathways leading to the oxidation of myoglobin to metmyoglobin with each required rate constant in 0.1 M buffer (pH 7.0) at 25 degrees C, and have set up six rate equations for the elementary processes going on in a simultaneous way. By using the Runge-Kutta method to solve these differential equations, the concentration progress curves were then displayed for all the reactive species involved. In this complex reaction, the primary event was the autoxidation of MbO2 to metMb with generation of the superoxide anion, this anion being converted immediately and almost completely into H2O2 by the spontaneous dismutation. Under air saturated conditions (PO2 = 150 Torr), the H2O2 produced was decomposed mostly by the metMb resulting from the autoxidation of MbO2. At lower pressures of O2, however, H2O2 can act as the most potent oxidant of the deoxyMb, which increases with decreasing O2 pressures, so that there appeared a well defined maximum rate in the formation of metMb at approximately 5 Torr of oxygen. Such examinations with the aid of a computer provide us, for the first time, with a full picture of the oxidation reaction of myoglobin as a function of oxygen pressures. These results also seem to be of primary importance from a point of view of clinical biochemistry of the oxygen supply, as well as of pathophysiology of ischemia, in red muscles such as cardiac and skeletal muscle tissues. PMID- 1420897 TI - Dimerization kinetics of the IgE-class antibodies by divalent haptens. I. The Fab hapten interactions. AB - The binding of divalent haptens to IgE-class antibodies leads predominantly to their oligomerization into open and closed dimers. Kinetics of the open dimer formation was investigated by fluorescence titrations of Fab fragments of monoclonal DNP-specific IgE antibodies with divalent haptens having different spacer length (gamma = 14-130 A). Binding was monitored by quenching of intrinsic tryptophan emission of the Fab. Addition of divalent haptens with short spacers (gamma = 14-21 A) to the Fabs at rates larger than a distinct threshold value caused a significant decrease of Fab-binding site occupation in the initial phase of the titration. This finding was interpreted to reflect a nonequilibrium state of hapten-Fab-binding. Such nonequilibrium titrations were analyzed by inserting a kinetic model into a theory of antibody aggregation as presented by Dembo and Golstein (Histamine release due to bivalent penicilloyl haptens. 1978. J. Immunol. 121, 345). Fitting of this model to the fluorescence titrations yielded dissociation rate constants of 7.8 x 10(-3) s-1 and 6 x 10(-3) s-1 for the Fab dimers formed by the flexible divalent haptens N alpha, N epsilon di(dinitrophenyl)-L-lysine (gamma = 16 A) and bis(N beta-2,4-dinitrophenyl alanyl)-meso-diamino-succinate (gamma = 21 A). Making the simplifying assumption that a single step binding equilibrium prevails, the corresponding dimer formation rate constants were calculated to be 1.9 x 10(5) M-1 s-1 and 1.1 x 10(4) M-1 s-1, respectively. In contrast, all haptens with spacers longer than 40 A (i.e., bis(N alpha-2,4-dinitrophenyl-tri-D-alanyl)-1,7-diamino-heptane, and di(N epsilon-2,4-dinitrophenyl)-6-aminohexanoate-aspartyl-(prolyl)n-L-l ysyl (n = 24, 27, 33) exhibit a relative fast dimerization rate of the Fab fragments (greater than 7 x 10(6) M-1 s-1). These observations were interpreted as being caused by orientational constraints set by the limited solid angle of the reaction between the macromolecular reactants. Thus, ligands having better access to the binding site would react faster. PMID- 1420898 TI - Dimerization kinetics of the IgE-class antibodies by divalent haptens. II. The interactions between intact IgE and haptens. AB - Interactions between a monoclonal, DNP-specific IgE molecules (hybridoma A2) and divalent DNP-haptens in solution cause aggregation of the former predominantly into closed rings of two IgE and two divalent haptens (Schweitzer-Stenner, R., A. Licht, I. Luscher, and I. Pecht. 1987. Biochemistry. 26:3602-3612). The time course of this process was now investigated by titrating the A2-IgE with divalent DNP-haptens having long and rigid oligoproline spacers (di(N epsilon-2,4 dinitrophenyl)-6-amino-hexanoate-aspartyl-(prolyl)n-L-ly- syl; n = 24, 27, 33). Binding was expressed in quenching of the IgE intrinsic tryptophan emission. As shown in the preceding paper, hapten addition to the IgE-A2 at rates faster than a distinct threshold value led to nonequilibrium titrations (NETs) from which kinetic processes slower than 2 s-1 can be resolved. Analysis of these titrations shows that the dimeric rings open at rates of approximately 10(-2) s-1, independent of the divalent hapten's spacer length. The ring closure rate, however, decreases with spacer length. The latter observation was qualitatively rationalized in terms of the diffusion process of a Gaussian chain which relates the ring closure rate constant to the expectation value for the distance between the free ends of the respective open chain. PMID- 1420899 TI - Magnetic and electric characteristics of the electric fish Gymnotus carapo. AB - The fresh water fish Gymnotus carapo produces a continuous series of weak pulsed electric fields in its surroundings and senses disturbances of this field as part of its sensory system. The electric and magnetic properties of the electric organ of this fish were studied. Magnetic fields close to the fish on the order of nT are produced by currents on the order of 10(-4) A in the electric organ of the fish. The electromotive force, the internal resistance, the current, and the electric power of the equivalent circuit were determined noninvasively. PMID- 1420900 TI - Protein dynamics and 1/f noise. AB - It has long been recognized that protein dynamical processes occur over a wide temporal range. However, the functionality of this spectrum of events remains unclear. In this work, a generalized noise function analysis is applied to a collection of diverse protein dynamical systems. It is shown that a power law model with an oscillatory component can adequately describe the time course of a variety of processes. These results suggest that under the appropriate conditions, proteins are in a metastable state. A microscopic, chemical kinetic model based on a Poisson distribution of activation energies is presented. From this model specific functional forms for the parameters of the generalized noise model can be derived. Additionally, a model is presented to described kinetic hole burning effects observed at low temperatures. Scaling laws are derived for these models that provide a connection with the generalized noise analysis. PMID- 1420901 TI - Oxygenation-deoxygenation cycle of erythrocytes modulates submicron cell membrane fluctuations. AB - Low frequency submicron fluctuations of the cell membrane were recently shown to be characteristic for different cell types, nevertheless their physiological role is yet unknown. Point dark-field microscopy based recordings of these local displacements of cell membrane in human erythrocytes, subjected to cyclic oxygenation and deoxygenation, reveals a reversible decrease of displacement amplitudes from 290 +/- 49 to 160 +/- 32 nm, respectively. A higher rate of RBC adhesion to a glass substratum is observed upon deoxygenation, probably due to a low level of fluctuation amplitudes. The variation in the amplitude of these displacements were reconstituted in open RBC ghosts by perfusing them with composite solutions of 2,3 diphosphoglycerate, Mg+2, and MgATP, which mimic the intracellular metabolite concentrations in oxygenated and deoxygenated erythrocytes. The mere change in intracellular Mg+2 during oxygenation deoxygenation cycle is sufficient to explain these findings. The results imply that the magnitude of fluctuations amplitude is directly connected with cell deformability. This study suggests that the physiological cycle of oxygenation deoxygenation provides a dynamic control of the bending deformability and adhesiveness characteristics of the RBC via a Mg+2-dependent reversible assembly of membrane-skeleton proteins. The existing coupling between oxygenation deoxygenation of the RBC and its mechanical properties is expected to play a key role in blood microcirculation and may constitute an example of a general situation for other circulating blood cells, where the metabolic control of cytoskeleton dynamics may modulate their dynamic mechanical properties. PMID- 1420902 TI - Modulation of lateral transport of membrane components by spatial variations in diffusivity and solubility. AB - The effect of spatially varying diffusivity and solubility on the efficiency of intramembrane transport is investigated by obtaining solutions to the generalized lateral diffusion equation in which both the diffusion coefficient, D(r), and the partition coefficient, K(r), are functions of position. The mean-time-to-capture by a sink, tc, of particles diffusing in a plane is obtained analytically for the case of a sink surrounded by gradients in D(r) and K(r) with radially symmetrical geometry. It is shown that for particles originating at random locations, tc is shortened dramatically, if in an annular region around the sink, D and K are significantly greater than in the remainder of the plane. Similarly, a viscous boundary layer surrounding a sink is demonstrated to represent a significant barrier for diffusing particles. To investigate more complex geometries, a finite difference numerical integration method is used and is shown to provide comparable results for tc with modest computational power. The same method is used to calculate the tc for particles originating at a source that is joined to the sink by a channel. The increase in the rate with which particles travel from a source to a sink when they are joined by a high diffusivity and/or solubility channel is illustrated by several numerical examples and by graphical representations that show the equilibrium particle density (and hence the effective particle flow) in the presence of different sink, source, and channel combinations. These results are discussed in terms of fluidity domains and other membrane heterogeneities. PMID- 1420903 TI - Kinetic analysis of the activation of transducin by photoexcited rhodopsin. Influence of the lateral diffusion of transducin and competition of guanosine diphosphate and guanosine triphosphate for the nucleotide site. AB - The activation of transducin (T) by photoexcited rhodopsin (R*) is kinetically dissected within the framework of Michaelis-Menten enzymology, taking transducin as substrate of the enzyme R*. The light scattering "release" signal (Vuong, T.M., M. Chabre, and L. Stryer, 1984, Nature (Lond.). 311:659-661) was used to monitor the kinetics of transducin activation at 20 degrees C. In addition, the influence of nonuniform distributions of R* on these activation kinetics is also explored. Sinusoidal patterns of R* were created with interference fringes from two crossed laser beams. Two characteristic times were extracted from the Michaelis-Menten analysis: t(form), the diffusion-related time needed to form the enzyme-substrate R*-transducin is 0.25 +/- 0.1 ms, and T(cat), the time taken by R* to perform the chemistry of catalysis on transducin is 1.2 +/- 0.2 ms, in the absence of added guanosine diphosphate (GDP) and at saturating levels of guanosine triphosphate (GTP). With t(form) being but 20% of the total activation time t(form) + t(cat), transducin activation by R* is not limited by lateral diffusion. This is further borne out by the observation that uniform and sinusoidal patterns of R* elicited release signals of indistinguishable kinetics. When (GDP) = (GTP) = 500 microM, t(cat) is lengthened twofold. As the in vivo GDP and GTP levels are comparable, the exchange of nucleotides may well be the rate limiting process. PMID- 1420904 TI - Direct observation of defect structure in protein crystals by atomic force and transmission electron microscopy. AB - We have examined the structure of S-layers isolated from Sulfolobus acidocaldarius using atomic force microscopy (AFM) and transmission electron microscopy (TEM). From the AFM images, we were able to directly observe individual dimers of the crystal, defects in the crystal structure, and twin boundaries. We have identified two types of boundaries, one defined by a mirror plane and the other by a glide plane. This work shows that twin boundaries are highly structured regions that are directly related to the organization of units within each crystal domain. Projection maps from TEM images have shown that there are significant differences in the final average maps has allowed us to relate high magnification views obtained by AFM to the relatively high resolution information obtained by electron microscopy and image processing. PMID- 1420905 TI - Rates of energy transfer between tryptophans and hemes in hemoglobin, assuming that the heme is a planar oscillator. AB - Using the Forster equations we have estimated the rate of energy transfer from tryptophans to hemes in hemoglobin. Assuming an isotropic distribution of the transition moments of the heme in the plane of the porphyrin, we computed the orientation factors and the consequent transfer rates from the crystallographic coordinates of human oxy- and deoxy-hemoglobin. It appears that the orientation factors do not play a limiting role in regulating the energy transfer and that the rates are controlled almost exclusively by the intrasubunit separations between tryptophans and hemes. In intact hemoglobin tetramers the intrasubunit separations are such as to reduce lifetimes to 5 and 15 ps/ns of tryptophan lifetime. Lifetimes of several hundred picoseconds would be allowed by the intersubunit separations, but intersubunits transfer becomes important only when one heme per tetramer is absent or does not accept transfer. If more than one heme per tetramer is absent lifetimes of more than 1 ns would appear. PMID- 1420906 TI - Quaternary structure and geminate recombination in hemoglobin: flow-flash studies on alpha 2CO beta 2 and alpha 2 beta 2CO. AB - The kinetics of geminate recombination for the diliganded species alpha 2CO beta 2 and alpha 2 beta 2CO of human hemoglobin were studied using flash photolysis. The unstable diliganded species were generated just before photolysis by chemical reduction in a continuous flow reactor from the more stable valency hybrids alpha 2CO beta 2+ and alpha 2+ beta 2CO, which could be prepared by high pressure liquid chromatography. Before the flash photolysis studies, the hybrids had been characterized by double-mixing stopped-flow kinetics experiments. At pH 6.0 in the presence of inositol hexaphosphate (IHP) both of the diliganded species show second order kinetics for overall addition of a third CO that is clearly characteristic of the T state (l' = 1-2 x 10(5) M-1 s-1), whereas at higher pH and in the absence of IHP they show combination rates characteristic of an R state. The kinetics of geminate recombination following photolysis of a bound CO, however, showed little dependence on pH and IHP concentration. This surprising observation is explained on the basis that the kinetics of geminate recombination of CO primarily depends on the tertiary structure of the ligand binding site, which apparently does not differ much between the R state and the liganded T state formed on adding IHP in this system. Since this explanation requires distinguishing different tertiary structures within a particular quaternary structure, it amounts to a contradiction to the two-state allosteric model. PMID- 1420907 TI - Vibrationally enhanced tunneling as a mechanism for enzymatic hydrogen transfer. AB - We present a theory of enzymatic hydrogen transfer in which hydrogen tunneling is mediated by thermal fluctuations of the enzyme's active site. These fluctuations greatly increase the tunneling rate by shortening the distance the hydrogen must tunnel. The average tunneling distance is shown to decrease when heavier isotopes are substituted for the hydrogen or when the temperature is increased, leading to kinetic isotope effects (KIEs)--defined as the factor by which the reaction slows down when isotopically substituted substrates are used--that need be no larger than KIEs for nontunneling mechanisms. Within this theory we derive a simple KIE expression for vibrationally enhanced ground state tunneling that is able to fit the data for the bovine serum amine oxidase (BSAO) system, correctly predicting the large temperature dependence of the KIEs. Because the KIEs in this theory can resemble those for nontunneling dynamics, distinguishing the two possibilities requires careful measurements over a range of temperatures, as has been done for BSAO. PMID- 1420908 TI - How do selectins mediate leukocyte rolling in venules? AB - At the onset of inflammation, 20-80% of all leukocytes passing postcapillary venules roll along the endothelium. Recent blocking experiments with antibodies and soluble adhesion receptor molecules, as well as in vitro reconstitution experiments, suggest that leukocyte rolling is mediated by adhesion molecules that belong to the selectin family. What differentiates a selectin counterreceptor interaction that leads to leukocyte rolling from others that mediate firm adhesion after static incubation but no adhesion when incubated under flow conditions? Here, we explore this question by introducing a quantitative biophysical model that is compatible with the laws of mechanics as applied to rolling leukocytes and the present biochemical and biophysical data on selectin mediated interactions. Our computational experiments point to an adhesion mechanism in which the rate of bond formation is high and the detachment rate low, except at the rear of the contact area where the stretched bonds detach at a high uniform rate. The bond length and bond flexibility play a critical role in enhancing leukocyte rolling at a wide range of fluid shear rates. PMID- 1420909 TI - Computer detection of the rapid diffusion of fluorescent membrane fusion markers in images observed with video microscopy. AB - We have developed an algorithm for automated detection of the dynamic pattern characterizing flashes of fluorescence in video images of membrane fusion. The algorithm detects the spatially localized, transient increases and decreases in brightness that result from the dequenching of fluorescent dye in phospholipid vesicles or lipid-enveloped virions fusing with a planar membrane. The flash is identified in video images by its nonzero time derivative and the symmetry of its spatial profile. Differentiation is implemented by forward and backward subtractions of video frames. The algorithm groups spatially connected pixels brighter than a user-specified threshold into distinct objects in forward- and backward-differentiated images. Objects are classified as either flashes or noise particles by comparing the symmetries of matched forward and backward difference profiles and then by tracking each profile in successive difference images. The number of flashes identified depends on the brightness threshold, the size of the convolution kernel used to filter the image, and the time difference between the subtracted video frames. When these parameters are changed so that the algorithm identifies an increasing percentage of the flashes recognized by eye, an increasing number of noise objects are mistakenly identified as flashes. These mistaken flashes can be eliminated by a human observer. The algorithm considerably shortens the time needed to analyze video data. Tested extensively with phospholipid vesicle and virion fusion with planar membranes, our implementation of the algorithm accurately determined the rate of fusion of influenza virions labeled with the lipophilic dye octadecylrhodamine (R18). PMID- 1420911 TI - Investigation of the structural determinants of the intrinsic fluorescence emission of the trp repressor using single tryptophan mutants. AB - The fluorescence decay properties of wild-type trp repressor (TR) have been characterized by carrying out a multi-emission wavelength study of the frequency response profiles. The decay is best analyzed in terms of a single exponential decay near 0.5 ns and a distribution of lifetimes centered near 3-4 ns. By comparing the recovered decay associated spectra and lifetime values with the structure of the repressor, tentative assignments of the two decay components recovered from the analysis to the two tryptophan residues, W19 and W99, of the protein have been made. These assignments consist of linking the short, red emitting component to emission from W99 and most of the longer bluer emitting lifetime distribution to emission from W19. Next, single tryptophan mutants of the repressor in which one of each of the tryptophan residues was substituted by phenylalanine were used to confirm the preliminary assignments, inasmuch as the 0.5-ns component is clearly due to emission from tryptophan 99, and much of the decay responsible for the recovered distribution emanates from tryptophan 19. The data demonstrate, however, that the decay of the wild-type protein is not completely resolvable due both to the large number of components in the wild-type emission (at least five) as well as to the fact that three of the five lifetime components are very close in value. The fluorescence decay of the wild-type decay is well described as a combination of the components found in each of the mutants. However, whereas the linear combination analysis of the 15 data sets (5 from the wild-type and each mutant) yields a good fit for the components recovered previously for the two mutants, the amplitudes of these components in the wild-type are not recovered in the expected ratios. Because of the dominance of the blue shifted emission in the wild-type protein, it is most likely that subtle structural differences in the wild-type as compared with the mutants, rather than energy transfer from tryptophan 19 to 99, are responsible for this failure of the linear combination hypothesis. PMID- 1420910 TI - Cooperativity of thiol-modified myosin filaments. ATPase and motility assays of myosin function. AB - The effects of chemical modifications of myosin's reactive cysteines on actomyosin adenosine triphosphatase (ATPase) activities and sliding velocities in the in vitro motility assays were examined in this work. The three types of modifications studied were 4-[N-[(iodoacetoxy)ethyl]-N-methylamino]-7-nitrobenz-2 oxa-1,3- diazole labeling of SH2 (based on Ajtai and Burghart. 1989. Biochemistry. 28:2204-2210.), phenylmaleimide labeling of SH1, and phenylmaleimide labeling of myosin in myofibrils under rigor conditions. Each type of modified myosin inhibited the sliding of actin in motility assays. The sliding velocities of actin over copolymers of modified and unmodified myosins in the motility assay were slowest with rigor-modified myosin and most rapid with SH2-labeled myosin. The actin-activated ATPase activities of similarly copolymerized myosins were lowest with SH2-labeled myosin and highest with rigor modified myosin. The actin-activated ATPase activities of myosin subfragment-1 obtained from these modified myosins decreased in the same linear manner with the fraction of modified heads. These results are interpreted using a model in which the sliding of actin filaments over myosin filaments decreases the probability of myosin activation by actin. The sliding velocity of actin over monomeric rigor modified myosin exceeded that over the filamentous form, which suggests for this myosin that filament structure is important for the inhibition of actin sliding in motility assays. The fact that all cysteine modifications examined inhibited the actomyosin ATPase activities and sliding velocities of actin over myosin poses questions concerning the information about the activated crossbridge obtained from probes attached to SH1 or SH2 on myosin. PMID- 1420912 TI - Lipid bilayer surface association of lung surfactant protein SP-B, amphipathic segment detected by flow immunofluorescence. AB - Lung surfactant protein, SP-B, and synthetic amphipathic peptides derived from SP B were studied in model lung surfactant lipid bilayers by immunofluorescent labeling. Liposomes were formed by hydrating a lipid film on the glass viewing port of a temperature controlled flow chamber. Membrane associated peptides were detected by epifluorescence optical microscopy of the binding of anti-peptide polyclonal monospecific antibodies and FITC-conjugated secondary antibodies added to buffer contained in the flow chamber. Liposomes were bound by antibody to residues 1-25 of SP-B if formed from lipid films containing the 1-25 peptide, (SP B(1-25)), or if SP-B(1-25) was added to already formed liposomes in buffer solution. The distribution of antigen-antibody complex was temperature dependent with aggregation occurring at greater than or equal to 30 degrees C. Surface association was not detected in liposomes formed from lipid films containing the 49-66 peptides (SP-B(49-66)), using an antibody to the 49-66 peptide, or to a synthetic version of the SP-B protein, (SP-B(1-78)), using both antibodies to the 49-66 peptide and the 1-25 peptide. The detection of SP-B(1-78) with antibody to the 49-66 sequence was only possible after reducing SP-B(1-78) with dithiothreitol, suggesting that the COOH-terminus of the full monomer protein is accessible to the bulk aqueous environment unlike the COOH-terminal peptide. The size, number of layers, and fluidity of the liposomes were not altered by protein or peptides, although they were affected by lipid composition and temperature. PMID- 1420913 TI - Influence of sickle hemoglobin polymerization and membrane properties on deformability of sickle erythrocytes in the microcirculation. AB - The rheological properties of normal erythrocytes appear to be largely determined by those of the red cell membrane. In sickle cell disease, the intracellular polymerization of sickle hemoglobin upon deoxygenation leads to a marked increase in intracellular viscosity and elastic stiffness as well as having indirect effects on the cell membrane. To estimate the components of abnormal cell rheology due to the polymerization process and that due to the membrane abnormalities, we have developed a simple mathematical model of whole cell deformability in narrow vessels. This model uses hydrodynamic lubrication theory to describe the pulsatile flow in the gap between a cell and the vessel wall. The interior of the cell is modeled as a Voigt viscoelastic solid with parameters for the viscous and elastic moduli, while the membrane is assigned an elastic shear modulus. In response to an oscillatory fluid shear stress, the cell--modeled as a cylinder of constant volume and surface area--undergoes a conical deformation which may be calculated. We use published values of normal and sickle cell membrane elastic modulus and of sickle hemoglobin viscous and elastic moduli as a function of oxygen saturation, to estimate normalized tip displacement, d/ho, and relative hydrodynamic resistance, Rr, as a function of polymer fraction of hemoglobin for sickle erythrocytes. These results show the transition from membrane to internal polymer dominance of deformability as oxygen saturation is lowered. More detailed experimental data, including those at other oscillatory frequencies and for cells with higher concentrations of hemoglobin S, are needed to apply fully this approach to understanding the deformability of sickle erythrocytes in the microcirculation. The model should be useful for reconciling the vast and disparate sets of data available on the abnormal properties of sickle cell hemoglobin and sickle erythrocyte membranes, the two main factors that lead to pathology in patients with this disease. PMID- 1420914 TI - Conformation and elasticity of the isolated red blood cell membrane skeleton. AB - We studied the structure and elasticity of membrane skeletons from human red blood cells (RBCs) during and after extraction of RBC ghosts with nonionic detergent. Optical tweezers were used to suspend individual cells inside a flow chamber, away from all surfaces; this procedure allowed complete exchange of medium while the low-contrast protein network of the skeleton was observed by high resolution, video-enhanced differential interference-contrast (DIC) microscopy. Immediately following extraction in a 5 mM salt buffer, skeletons assumed expanded, nearly spherical shapes that were uncorrelated with the shapes of their parent RBCs. Judging by the extent of thermal undulations and by their deformability in small flow fields, the bending rigidity of skeletons was markedly lower than that of either RBCs or ghosts. No further changes were apparent in skeletons maintained in this buffer for up to 40 min at low temperatures (T less than 10 degrees C), but skeletons shrank when the ionic strength of the buffer was increased. When the salt concentration was raised to 1.5 M, shrinkage remained reversible for approximately 1 min but thereafter became irreversible. When maintained in 1.5 M salt buffer for longer periods, skeletons continued to shrink, lost flexibility, and assumed irregular shapes: this rigidification was irreversible. At this stage, skeletons closely resembled those isolated in standard bulk preparations. We propose that the transformation to the rigid, irreversibly shrunken state is a consequence of spectrin dimer dimer reconnections and that these structural rearrangements are thermally activated. We also measured the salt-dependent size of fresh and bulk extracted skeletons. Our measurements suggest that, in situ, the spectrin tethers are flexible, with a persistence length of approximately 10 nm at 150 mM salt. PMID- 1420915 TI - Time-resolved x-ray diffraction study of the troponin-associated reflexions from the frog muscle. AB - The vertebrate skeletal muscle gives rise to a series of x-ray reflexions indexed as orders (n) of 77 nm, the even orders being meridional whereas the odd orders being near-meridional. The diffraction intensities associated with these reflexions originate from the axial period of 39 nm attributable to the repeat of troponin-tropomyosin on the thin filament. In the present study, the x-ray intensities of the furthest inner reflexions, A2 (n = 2) reflexion at an axial spacing of 1/39 nm-1 and A4 (n = 4) reflexion at 1/19 nm, of this series were measured with a time resolved manner. Upon activation of the frog striated muscle, the two reflexions underwent biphasic time courses of the intensity changes. With A2 reflexion, a rapid intensity increase by 16%, being completed by the time when tension rises to 5%, was followed by a slow intensity decrease down to 50%, which was associated with the tension rise. In both phases, lateral widths remained unchanged. A4 reflexion also behaves in the same way, although the first phase (the intensity increase) was not clear due to unsatisfactory statistics. We interpret phase one as being caused by conformational change of the troponin-tropomyosin complex upon binding of Ca2+ to troponin, whereas phase two being due to direct contribution of the mass of the myosin heads bound to the thin filament, although possible contribution of conformational changes of the regulatory proteins to phase two is not excluded. The results indicated that the calcium activation of the thin filament leads the onset of the actomyosin interaction. PMID- 1420916 TI - Quenching of fluorescein-conjugated lipids by antibodies. Quantitative recognition and binding of lipid-bound haptens in biomembrane models, formation of two-dimensional protein domains and molecular dynamics simulations. AB - Three model biomembrane systems, monolayers, micelles, and vesicles, have been used to study the influence of chemical and physical variables of hapten presentation at membrane interfaces on antibody binding. Hapten recognition and binding were monitored for the anti-fluorescein monoclonal antibody 4-4-20 generated against the hapten, fluorescein, in these membrane models as a function of fluorescein-conjugated lipid architecture. Specific recognition and binding in this system are conveniently monitored by quenching of fluorescein emission upon penetration of fluorescein into the antibody's active site. Lipid structure was shown to play a large role in affecting antibody quenching. Interestingly, the observed degrees of quenching were nearly independent of the lipid membrane model studied, but directly correlated with the chemical structure of the lipids. In all cases, the antibody recognized and quenched most efficiently a lipid based on dioctadecylamine where fluorescein is attached to the headgroup via a long, flexible hydrophilic spacer. Dipalmitoyl phosphatidylethanolamine containing a fluorescein headgroup demonstrated only partial binding/quenching. Egg phosphatidylethanolamine with a fluorescein headgroup showed no susceptibility to antibody recognition, binding, or quenching. Formation of two-dimensional protein domains upon antibody binding to the fluorescein-lipids in monolayers is also presented. Chemical and physical requirements for these antibody-hapten complexes at membrane surfaces have been discussed in terms of molecular dynamics simulations based on recent crystallographic models for this antibody-hapten complex (Herron et al., 1989. Proteins Struct. Funct. Genet. 5:271-280). PMID- 1420917 TI - Conformational dynamics and intersubunit energy transfer in wild-type and mutant lipoamide dehydrogenase from Azotobacter vinelandii. A multidimensional time resolved polarized fluorescence study. AB - Time-resolved fluorescence and fluorescence anisotropy data surfaces of flavin adenine dinucleotide bound to lipoamide dehydrogenase from Azotobacter vinelandii in 80% glycerol have been obtained by variation of excitation energy and temperature between 203 and 303 K. The fluorescence kinetics of a deletion mutant lacking 14 COOH-terminal amino acids were compared with the wild-type enzyme to study a possible interaction of the COOH-terminal tail with the active site of the enzyme. The flavin adenine dinucleotide fluorescence in both proteins exhibits a bimodal lifetime distribution as recovered by the maximum entropy method of data analysis. The difference in standard enthalpy and entropy of associated conformational substates was retrieved from the fractional contributions of the two lifetime classes. Activation energies of thermal quenching were obtained that confirm that the isoalloxazines in the deletion mutant are solvent accessible in contrast to the wild-type enzyme. Red-edge spectroscopy in conjunction with variation of temperature provides the necessary experimental axes to interpret the fluorescence depolarization in terms of intersubunit energy transfer rather than reorientational dynamics of the flavins. The results can be explained by a compartmental model that describes the anisotropy decay of a binary, inhomogeneously broadened, homoenergy transfer system. By using this model in a global analysis of the fluorescence anisotropy decay surface, the distance between and relative orientation of the two isoalloxazine rings are elucidated. For the wild-type enzyme, this geometrical information is in agreement with crystallographic data of the A. vinelandii enzyme, whereas the mutual orientation of the subunits in the deletion mutant is slightly altered. In addition, the ambiguity in the direction of the emission transition moment in the isoalloxazine ring is solved. The anisotropy decay parameters also provide information on electronic and dipolar relaxational properties of the flavin active site. The local environment of the prosthetic groups in the deletion mutant of the A. vinelandii enzyme is highly inhomogeneous, and a transition from slow to rapid dipolar relaxation is observed over the measured temperature range. In the highly homogeneous active site of the wild-type enzyme, dipolar relaxation is slowed down beyond the time scale of fluorescence emission at any temperature studied. Our results are in favor of a COOH-terminal polypeptide interacting with the active site, thereby shielding the isoalloxazines from the solvent. This biological system forms a very appropriate tool to test the validity of photophysical models describing homoenergy transfer. PMID- 1420918 TI - Simplified method for setting the phase angle used in capacitance measurements in studies of exocytosis. AB - Phase detectors (lock-in amplifiers) have been used in conjunction with patch clamp apparatus to follow the time course of exo- and endocytotic processes. A critical step is accurate setting of the phase to separate signals due to conductance changes from those due to capacitance changes. It has been the practice to obtain this setting empirically. Analysis of the admittance, and its derivatives, of a model equivalent circuit used commonly in this field shows that the desired phase setting is just twice the phase shift of the current relative to the stimulus voltage, which is easily, accurately and quickly determined. This fact permits rapid and accurate setting of the desire phase angle for those cells to which the equivalent circuit is suitable. PMID- 1420919 TI - Penetration of macromolecules into contracted blood clot. AB - The effectiveness of thrombolytic therapy is determined by accessibility of thrombus compartments to plasminogen activators and, therefore, depends on permeability of thrombus to blood born macromolecules. Accumulation of 125I labeled proteins with molecular massess ranging from 150 to 450 kD into partly contracted blood clot or plasma clot was consistent with diffusion coefficients 3.2 x 10(-11) and 2.7 x 10(-11) m2 s-1, respectively. So far as the model conditions imitated those for venous thrombi, these data indicate that such thrombi are porous enough for immunoconjugates of relatively big size. PMID- 1420920 TI - Studies on the structure of actin gels using time correlation spectroscopy of fluorescent beads. AB - Fluorescence correlation spectroscopy (FCS) has been used to measure the diffusion of fluorescently labeled beads in solutions of polymerized actin or buffer. The results, obtained at actin concentrations of 1 mg/ml, show that small beads (0.09 micron in diameter) diffuse nearly as rapidly in the actin gel as in buffer, whereas the largest beads tested (0.5 micron in diameter) are immobilized. Measured autocorrelation times for motions of beads with intermediate sizes show that the diffusion is retarded (relative to buffer) and that the time behavior cannot be represented as a single diffusive process. In addition to the retarded diffusion observed over distances > 1 micron, 0.23 micron beads also show a faster motion over smaller distances. Based on the measured rate of this faster motion, we estimate that the beads may be constrained within a cage approximately 0.67 micron on a side, equal to a filament length of approximately 250 subunits. Fluorescence correlation spectroscopy measurements made in the same small spot (radius of 1.4 microns) of the gel vary over time. From the variations of both the autocorrelation functions and the mean fluorescence, we conclude that, corresponding to a spatial scale of 1.4 microns, the actin gel is a dynamic structure with slow rearrangement of the gel occurring over periods of 20-50 s at 21-22 degrees C. This rearrangement may result from local reorganization of the actin matrix. Data for the retardation of beads by the actin gel are consistent with a detailed theory of the diffusion of particles through solutions of rigid rods that have longitudinal diffusion coefficients much less than that of the particles (Ogston, A. G., B. N. Preston, and J. D. Wells. 1973. Proc. R. Soc. Lond. A. 333:297-316). PMID- 1420921 TI - Effects of the anesthetic dibucaine on the kinetics of the gel-liquid crystalline transition of dipalmitoylphosphatidylcholine multilamellar vesicles. AB - The effects of the anesthetic dibucaine on the relaxation kinetics of the gel liquid crystalline transition of dipalmitoylphosphatidylcholine (DC16PC) multilamellar vesicles have been investigated using volume-perturbation calorimetry. The temperature and pressure responses to a periodic volume perturbation were measured in real time. Data collected in the time domain were subsequently converted into and analyzed in the frequency domain using Fourier series representations of the perturbation and response functions. The Laplace transform of the classical Kolmogorov-Avrami kinetic relation was employed to describe the relaxation dynamics in the frequency domain. The relaxation time of anesthetic-lipid mixtures, as a function of the fractional degree of melting, appears to be qualitatively similar to that of pure lipid systems, with a pronounced maximum, tau max, observed at a temperature corresponding to greater than 75% melting. The tau max decreases by a factor of approximately 2 as the nominal anesthetic/lipid mole ratio increases from 0 to 0.013 and exhibits no further change as the nominal anesthetic/lipid mole ratio is increased. However, the fractional dimensionality of the relaxation process decreases monotonically from slightly less than two to approximately one as the anesthetic/lipid mole ratio increases from 0 to 0.027. At higher ratios, the dimensionality appears to be less than one. These results are interpreted in terms of the classical kinetic theory and related to those obtained from Monte Carlo simulations. Specifically, low concentrations of dibucaine appear to reduce the average cluster size and cause the fluctuating lipid clusters to become more ramified. At the highest concentration of dibucaine, where n < 1, the system must be kinetically heterogeneous. PMID- 1420922 TI - Study of mechanisms of electric field-induced DNA transfection. IV. Effects of DNA topology on cell uptake and transfection efficiency. AB - Electric parameters and solvent conditions are known to influence the efficiency of DNA transfection of cells by a pulsed electric field (PEF). A previous study (Neumann, E., M. Schaefer-Ridder, Y. Wang, and P. H. Hofschneider. 1982. EMBO (Eur. Mol. Biol. Organ.) J. 1:841-845) has indicated that DNA topology is also an important determinant. We report an investigation of the PEF induced uptake, stability, and expression of three different topological isomers, circular supercoiled (scDNA), circular relaxed (crDNA), and linearized (lnDNA) forms of the plasmid pBR322, by Escherichia coli strain JM105. Monomeric pBR322 prepared by the electroelution from an agarose gel was in the supercoiled form. Treatment of the scDNA with wheat germ topoisomerase I removed the superhelicity and the DNA assumed the relaxed circular form. Treatment of scDNA by a restriction endonuclease, EcoRI or Hind III, linearized the DNA. The MgCl2-dependent bindings of all three forms of DNA to the cell surface were indistinguishable. So was the PEF induced cell uptake. In contrast, the transfection efficiency (TE) for the scDNA and the crDNA were high (approximately 2 x 10(8) micrograms-1 DNA at neutral pH), whereas that for the lnDNA was approximately five orders of magnitude lower (less than 1 x 10(3) micrograms-1 DNA). Analysis by agarose gel electrophoresis indicated that the PEF loaded ln DNA was degraded by the host cell within 3 h. However, the loaded scDNA and the crDNA were stable and expressed in the cytoplasm. We conclude that first, the PEF induced DNA entry into E. coli did not depend on the topology of the DNA. As cellular uptake of DNA also correlated with the surface binding, these data support electrophoresis of surface bound DNA as the dominating mechanism for the DNA entry. Second, the variations of TE for different topological forms of DNA reflected their relative stability in the host cells. Third, since the loaded DNA could be either rapidly degraded by the host enzyme or expressed, they were unlikely coated with a layer of protective lipid membrane. Thus, PEF induced cellular uptake of DNA is unlikely by the endocytotic mechanisms as was reported previously for the liposomes (Chernomordik, L. V., A. V. Sokolov, and V. G. Budker. 1990.Biochim. Biophys. Acta. 1024:179-183). PMID- 1420923 TI - Shaking stack model of ion conduction through the Ca(2+)-activated K+ channel. AB - Motivated by the results of Neyton and Miller (1988. J. Gen. Physiol. 92:549 586), suggesting that the Ca(2+)-activated K+ channel has four high affinity ion binding sites, we propose a physically attractive variant of the single-vacancy conduction mechanism for this channel. Simple analytical expressions for conductance, current, flux ratio exponent, and reversal potential under bi-ionic conditions are found. A set of conductance data are analyzed to determine a realistic range of parameter values. Using these, we find qualitative agreement with a variety of experimental results previously reported in the literature. The exquisite selectivity of the Ca(2+)-activated K+ channel may be explained as a consequence of the concerted motion of the "stack" in the proposed mechanism. PMID- 1420924 TI - Acyl chain conformational ordering in 1,2 dipalmitoylphosphatidylethanolamine. Integration of FT-IR and 2H NMR results. AB - The extent of trans-gauche isomerization at the 4 and 4' positions of the acyl chains of fully hydrated 4,4,4',4'-d4 1,2-dipalmitoylphosphatidylethanolamine (4 d4 DPPE) bilayers was quantitatively evaluated from the infrared (IR) intensity of the CD2 rocking modes. About 20% gauche conformers were observed at 72 degrees C (above Tm), while at 23 degrees C, well below Tm, about 4% were noted. The order parameter SC-D was determined from 2H nuclear magnetic resonance (NMR) quadrupolar splittings. SC-D is the product of a segmental order parameter (S gamma), which depends on conformational order, and a chain order parameter (S alpha) which depends on slower motions such as chain wobble. The IR-determined percentage of gauche forms was converted into a segmental order parameter and factored out of the measured value for SC-D to yield an estimate of S alpha = 0.59 for L alpha phase DPPE. A comparison with S alpha for 1,2 dipalmitoylphosphatidylcholine (DPPC) suggests that increased wobble is responsible for enhanced motional averaging of the quadrupolar splittings in the latter at a similar reduced temperature. The extent of conformational disordering [at the 4(4') position] is essentially unchanged between the two molecules. The current study demonstrates the advantage of integrating quantitative IR with 2H NMR data, for elucidation of the contributions of the individual motions that average the NMR quadrupolar splittings. PMID- 1420926 TI - Adenine nucleotide translocase greatly increases the partition of trinitrophenyl ATP into reduced Triton X-100 micelles. AB - The presence of adenine nucleotide translocase (ANT) was found to greatly enhance the partitioning of the ATP analog 2',3'-O-(2,4,6-trinitrophenyl)-adenosine 5' triphosphate (TNP-ATP) into reduced Triton X-100 micelles. The protein's effect was studied through the quenching of fluorescence of purified ANT, irreversibly inhibited by carboxyatractyloside (CAT), solubilized in reduced Triton X-100 micelles. The dependence of quenching of the protein's time-resolved tryptophan fluorescence on TNP-ATP concentration was measured and found to follow a Stern Volmer mechanism. However, the calculated quenching constant was too large to be accounted for by the aqueous TNP-ATP concentration. Experiments were therefore conducted to determine the partitioning of the quencher between the three phases present: aqueous, protein-free micelle, and protein micelle; a system also described by the equation of Omann, G. M., and M. Glaser (1985. Biophys. J. 47:623-627.). By measuring the dependence of the apparent quenching rate constant on the protein concentration and protein/micelle ratios, this equation was used to calculate both the quencher partition coefficient into protein-free micelles (Pm) and into protein-micelles (Ppm), as well as the bimolecular quenching rate constant (kpm) in protein micelles. From the quenching experiments, kpm = 5.0 x 10(8)M-1s-1,Pm = 290 and pyrene quenching experiment to be 325, and by a rapid filtration experiment to be 450. Clearly, the presence of the integral membrane protein ANT-CAT in reduced Triton X-100 micelles greatly increases the partition of TNP-ATP into the micelle. ANT alters the properties and thus, the structure of the detergent micelle, which has direct implications for the use of detergent micelles as a model system for membrane proteins and may indicate that analogous effects occur in the mitochondrial membrane. PMID- 1420925 TI - A mosaic multiple-binding model for the binding of caldesmon and myosin subfragment-1 to actin. AB - Binding of caldesmon to actin causes a decrease in the quantity of bound myosin and results in a reduction in the rate of actin-activated adenosine triphosphate hydrolysis. It is generally assumed that the binding of caldesmon and myosin to actin is a pure competitive interaction. However, recent binding studies of enzyme digested caldesmon subfragments directed at mapping the actin binding site of caldesmon have shown that a small 8-kD fragment around the COOH-terminal can compete directly with the myosin subfragment 1 (S-1) binding to actin; at least one other fragment that binds to actin does not inhibit the actin-activated adenosine triphosphate activity of myosin. That is, only a part of the caldesmon sequence may be responsible for directly blocking the binding of S-1 to actin. This prompts us to question the actual mode of binding of intact caldesmon and myosin S-1 to actin: whether the entire intact caldesmon molecule is competing with S-1 binding (pure competitive model) or just a small part of it (mosaic multiple-binding model). To answer this question, we measured the amount of myosin S-1 and caldesmon bound per actin monomer as a function of the total concentration of S-1 added to the system at constant concentrations of actin and caldesmon. A formalism for calculating the titration data based on the pure competitive model and a mosaic multiple-binding model was then developed. When compared with theoretical calculations, it is found that the binding of caldesmon and S-1 to actin cannot be pure competitive if no cooperativity exists between S 1 and caldesmon. In contrast, the mosaic multiple-binding model can fit the binding data rather well regardless of the existence of cooperativity between S-1 and caldesmon. PMID- 1420928 TI - Confinement as a determinant of macromolecular structure and reactivity. AB - The confinement of macromolecules within enclosures or "pores" of comparable dimensions results in significant size- and shape-dependent alterations of macromolecular chemical potential and reactivity. Calculations of the magnitude of this effect for model particles of different shapes in model enclosures of different shapes were carried out using hard particle partition theory developed by Giddings et al. (J. Phys. Chem. 1968. 72:4397-4408). Results obtained indicate that the equilibrium constants of reactions, such as isomerization, self association, and site binding, that result in significant change in macromolecular size, shape, and/or mobility may be altered within pores by as much as several orders of magnitude relative to the value in the unbounded or bulk phase. Confinement also produces a substantial size-dependent outward force on the walls of an enclosure. These results are likely to be important within the fluid phase of biological media, such as the cytoplasm of eukaryotic cells, containing significant volume fractions of large fibrous structures (e.g., the cytomatrix). PMID- 1420927 TI - Cholesterol in model membranes. A molecular dynamics simulation. AB - Molecular dynamics simulations of a model membrane with inserted cholesterol molecules have been performed to study the perturbing influence of cholesterol. In the fluid phase of a lipid bilayer at 13 mol% concentration of cholesterol, local ordering of the hydrocarbon chains is induced. This perturbation decays with the distance from the cholesterol, and the effect extends 1.25 nm. It can be monitored in several ways, e.g., by an order parameter corresponding to deuterium nuclear magnetic resonance quadrupolar splittings, by the fraction of gauche bonds, or by the local bilayer thickness. At constant surface density, the local ordering is accompanied by disordering of the bulk phase, and, consequently, the net ordering effect is small. After compressing the system laterally in accordance with experimentally known surface areas, the bulk order parameters agree with those of a pure system, and the average order parameters are in accordance with experimental data. The necessity for this lateral compression is supported by calculated lateral pressures. At lower cholesterol concentration (3%), no direct perturbing effect is observed. A smaller lateral pressure than in a pure system indicates that the system with cholesterol is expected to have a smaller surface area, which would result in an increase of the order parameters, thus accounting for the experimental observations. The lack of spatial variation is, however, puzzling and may indicate a cooperative ordering effect. PMID- 1420929 TI - Interfacial models of nerve fiber cytoskeleton. AB - A new approach, basing on a resemblance between cytoskeleton structures associated with plasma membranes and interfacial layers of coexisting phases, is proposed. In particular, a lattice model, similar to those of the theory of surface properties of pure liquids and nonelectrolyte solutions (Ono, S., and S. Kondo. 1960. Handbuch der Physik.), has been developed to describe nerve fiber cytoskeleton. The preliminary consideration of the model shows the existence of submembrane cytoskeleton having increased peripheral densities of microtubules (compared with the bulk density) which is in qualitative agreement with the data in literature. Some additional possibilities of the approach proposed are briefly discussed. PMID- 1420930 TI - The exocytotic fusion pore modeled as a lipidic pore. AB - Freeze-fracture electron micrographs from degranulating cells show that the lumen of the secretory granule is connected to the extracellular compartment via large (20 to 150 nm diameter) aqueous pores. These exocytotic fusion pores appear to be made up of a highly curved bilayer that spans the plasma and granule membranes. Conductance measurements, using the patch-clamp technique, have been used to study the fusion pore from the instant it conducts ions. These measurements reveal the presence of early fusion pores that are much smaller than those observed in electron micrographs. Early fusion pores open abruptly, fluctuate, and then either expand irreversibly or close. The molecular structure of these early fusion pores is unknown. In the simplest extremes, these early fusion pores could be either ion channel like protein pores or lipidic pores. Here, we explored the latter possibility, namely that of the early exocytotic fusion pore modeled as a lipid-lined pore whose free energy was composed of curvature elastic energy and work done by tension. Like early exocytotic fusion pores, we found that these lipidic pores could open abruptly, fluctuate, and expand irreversibly. Closure of these lipidic pores could be caused by slight changes in lipid composition. Conductance distributions for stable lipidic pores matched those of exocytotic fusion pores. These findings demonstrate that lipidic pores can exhibit the properties of exocytotic fusion pores, thus providing an alternate framework with which to understand and interpret exocytotic fusion pore data. PMID- 1420932 TI - Measuring the microelastic properties of biological material. AB - We have used the atomic force microscope (AFM) to measure the local rigidity modulus at points on the surface of a section of hydrated cow tibia. These data are obtained either from contrast changes that occur as the contact force is altered, or from force versus distance curves obtained at fixed points. These two methods yield the same values for rigidity modulus (at a given point). At low resolution, the elastic morphology and topography mirror the features seen in optical and electron micrographs. At high resolution we see dramatic variations in elastic properties across distances as small as 50 nm. PMID- 1420931 TI - Evaluation of cellular mechanisms for modulation of calcium transients using a mathematical model of fura-2 Ca2+ imaging in Aplysia sensory neurons. AB - A theoretical model of [Ca++]i diffusion, buffering, and extrusion was developed for Aplysia sensory neurons, and integrated with the measured optical transfer function of our fura-2 microscopic recording system, in order to fully simulate fura-2 video or photomultiplier tube measurements of [Ca++]i. This allowed an analysis of the spatial and temporal distortions introduced during each step of fura-2 measurements of [Ca++]i in cells. In addition, the model was used to evaluate the plausibility of several possible mechanisms for modulating [Ca++]i transients evoked by action potentials. The results of the model support prior experimental work (Blumenfeld, Spira, Kandel, and Siegelbaum, 1990. Neuron. 5: 487-499), suggesting that 5-HT and FMRFamide modulate action potential-induced [Ca++]i transients in Aplysia sensory neurons through changes in Ca++ influx, and not through changes in [Ca++]i homeostasis or release from internal stores. PMID- 1420933 TI - Fatty-acid chain tilt angles and directions in dipalmitoyl phosphatidylcholine bilayers. AB - X-ray diffraction has been applied to determine the various tilt angles and directions (if any) which can be assumed by oriented gel phase multilayers of dipalmitoyl phosphatidylcholine (DPPC) as a function of hydration. We report for the first time that oriented DPPC multilayers with a repeat spacing (d-spacing) of 55.2A at 25 degrees C and 0% relative humidity (RH) have hydrocarbon chains tilted at an angle theta of 21.5 degrees with respect to the bilayer normal. In addition, the chains are tilted along one of the bisectors (omega = 0 degrees) of the hexagonal lattice (8 wide-angle maxima, 2 unique), a phase not previously reported in DPPC studies. At 100% RH, the chain tilt angle and d-spacing increased to approximately 29.0 degrees and 58.9A, respectively. Since at 100% RH only 4 wide-angle maxima are observed, we analyze the data on the assumption that the hydrocarbon chains may rotate independently of the hexagonal lattice (omega = 0-30 degrees), at a fixed chain tilt angle theta (Stamatoff, J.B., et al. 1979. Biophys. J. 25:253-262). The largest observed angle phi made by the wide-angle maxima with the equator is 29.5 degrees corresponding to a theta of approximately 32.6 degrees (omega avg. = 24 degrees) and the sample having a d-spacing of 64.0 A (excess water condition). Finally, theta remains relatively constant (approximately 21.5 degrees) up to a RH of approximately 45% and a d-spacing of 57.8A, after which, with increases in RH, theta increases to a maximum of 32.6 degrees. PMID- 1420934 TI - E/M dips. Evidence for lipids regularly distributed into hexagonal super-lattices in pyrene-PC/DMPC binary mixtures at specific concentrations. AB - We have examined the effect of 1-palmitoyl-2-(10-pyrenyl)decanoyl-sn-glycerol-3 phosphatidylcholine (Pyr-PC) concentration on the ratio of excimer fluorescence to monomer fluorescence (E/M) in L-alpha-dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles at 30 degrees C, with special attention focussed on the smoothness of the curve. We observed a series of dips, in addition to kinks, in the plot of E/M versus the mole fraction of Pyr-PC (XPyrPC). The observation of dips is a new finding, perhaps unique for Pyr-PC in DMPC since only kinks were observed for Pyr-PC in L-alpha-dipalmitoylphosphatidylcholine (DPPC) and in egg yolk phosphatidylcholine (egg-PC) (Somerharju et al., 1985. Biochemistry. 24: 2773-2781). The dips/kinks observed here are distributed according to a well defined pattern reflecting a lateral order in the membrane, and distributed symmetrically with respect to 50 mol% Pyr-PC. Some of the dips appear at specific concentrations (YPyrPC) according to the hexagonal super-lattice model proposed by Virtanen et al. (1988. J. Mol. Electr. 4: 233-236). However, the observations of dips at XPyrPC > 66.7 mol% and the kink at 33.3 mol% cannot be interpreted by the model of Virtanen et al. (1988). These surprising results can be understood by virtue of an extended hexagonal super-lattice model, in which we have proposed that if the pyrene-containing acyl chains are regularly distributed as a hexagonal super-lattice in the DMPC matrix at a specific concentration YPyrPC, then the acyl chains of DMPC can form a regularly distributed hexagonal super lattice in the membrane at a critical concentration (1-YPyrPC). The excellent agreement between the calculated and the observed dip/kink positions, except for the dip at 74 mol% and the kink at 40 mol%, provides most compelling evidence that lipids are regularly distributed into hexagonal super-lattices in Pyr PC/DMPC mixtures at specific concentrations. The physical nature of the dips not only gives us a better understanding of lipid lateral organization in membranes but also will lead to new theoretical considerations and experimental designs for exploring the relationship between lipid regular distribution and membrane functions. PMID- 1420935 TI - Rotational diffusion and intermolecular collisions of a spin labeled alpha helical peptide determined by electron spin echo spectroscopy. AB - Short peptides that are composed mainly of alanine have recently been shown to form alpha-helices in aqueous solution at low temperature (Marqusee, S., and R. L. Baldwin. 1987. Proc. Natl. Acad. Sci. 84:8898-8902; Marqusee, S., V. H. Robbins, and R. L. Baldwin. 1989. Proc. Natl. Acad. Sci. USA. 86:5286-5290). These peptides are excellent models for probing structure and dynamics in isolated helical domains. In previous work we have designed and synthesized spin labeled analogs of these helix-forming peptides and we have shown that these analogs retain the folding characteristics of the parent peptide (Todd, A. P., and G. L. Millhauser. 1991. Biochemistry. 30:5515-5523). Using conventional continuous wave electron spin resonance (CW ESR) we have further shown that local motion is more pronounced near the helix amino terminus than in the central region as the peptide is thermally unfolded (Miick, S. M., A. P. Todd, and G. L. Millhauser. 1991. Biochemistry. 30:9498-9503). In this present work we use electron spin echo (ESE) spectroscopy to further refine our understanding of the solution dynamics of the 3K-8 peptide, which is a 16-mer with a nitroxide spin label attached at position 8. We find that the spin echo decays are well described by a single exponential function and that the determined correlation times are close to those previously derived from CW experiments. Variable concentration ESE experiments have directly revealed Heisenberg spin exchange (HSE) interactions and we find that the interpeptide collision rate is near to that expected for a free species in solution. This provides strong evidence that the helical conformation of these peptides is not stabilized by intermolecular interactions. PMID- 1420936 TI - Molecular origin of the internal dipole potential in lipid bilayers: calculation of the electrostatic potential. AB - The finite difference linearized Poisson-Boltzmann equation was solved for a segment of bilayer for two lipids (phosphatidylcholine dihydrate and phosphatidylethanolamine-acetic acid) in order to obtain the transbilayer electrostatic potential. Atomic coordinates derived from the crystal structures of these lipids were used, and partial changes were assigned to all atoms in the polar parts of the molecules. These calculations confirmed that a dipole potential exists in the uncharged hydrophobic interior of a bilayer. The phosphocholine and phosphoethanolamine groups make negative contributions to the internal potential, and the glycerol acyl esters make positive contributions, but the sum of these terms is negative. The water of hydration in phosphatidylcholine, and the acetic acid which is present in the phosphatidylethanolamine crystal structure, make positive contributions to the internal potential. It is concluded that the water of hydration in fully hydrated lipid bilayers is mainly responsible for the experimentally inferred positive sign of the internal potential. PMID- 1420938 TI - A theoretical model of LDL-receptor trapping on a spherical cell. AB - The kinetics of the trapping of LDL-receptor complexes by coated pits on the surface of fibroblasts is examined in this paper. We have recently developed a mathematical formalism to extend Keizer's non-linear, non-equilibrium fluctuation dissipation theory to the kinetics of chemical systems constrained to a spherical surface. Keizer's theory is ideally suited to the study of open biological systems. In the past it has been used to investigate endocytosis on fibroblasts. However, these applications have modeled the cell membrane with an infinite plane. As such, the finite size of the cellular membrane, as well as its precise symmetry, could not be incorporated into the previous studies. Thus in this paper we use our recently developed methodology to reexamine the trapping step in endocytosis on spherical cells. For cell surface processes, the theoretical consideration of a spherical symmetry or an infinite plane, in model calculations, will depend on the experimental or in vivo conditions of the processes of interest. For a spherical symmetry, we find that the finite size of the cell surface does not significantly affect the rate of the trapping step given the empirically determined values for the relevant parametes on fibroblasts. This result supports the approximation used in the previous investigation. However, this and other analyses indicate that the finitie size of the biological surface probably is an important parameter for processes which occur on smaller biological surfaces such as those found on organelles. PMID- 1420937 TI - Time-resolved tryptophan emission study of cardiac troponin I. AB - We have carried out a time-resolved fluorescence study of the single tryptophanyl residue (Trp-192) of bovine cardiac Tnl (CTnl). With excitation at 300 nm, the intensity decay was resolved into three components by a nonlinear least-squares analysis with lifetimes of 0.60, 2.22, and 4.75 ns. The corresponding fractional amplitudes were 0.27, 0.50, and 0.23, respectively. These decay parameters were not sensitive to complexation of CTnl with cardiac troponin C (CTnC), and magnesium and calcium had no significant effect on the decay parameters. After incubation with 3':5'-cyclic AMP-dependent protein kinase, the intensity decay of CTnl required a fourth exponential term for satisfactory fitting with lifetimes of 0.11, 0.81, 1.95, and 6.63 ns and fractional amplitudes of 0.06, 0.37, 0.27, and 0.29, respectively. When bound to CTnC, the intensity decay of phosphorylated CTnl (p-CTnl) also required four exponential terms for satisfactory fitting, but the longest lifetime increased by a factor of 1.7. The decay parameters obtained from the complex formed between p-CTnl and CTnC were not sensitive to either magnesium or calcium. The anisotropy decay was resolved into two components with rotational correlation times of 0.90 and 23.48 ns. Phosphorylation resulted in a decrease of the long correlation time to 14.61 ns. The anisotropy values recovered at zero time suggest that the side chain of the Trp-192 had considerable subnanosecond motional freedom not resolved in these experiments. Within the CTnl.CTnC complex, the unresolved fast motions appeared sensitive to calcium binding to the calcium-specific site of CTnC. The observed emission heterogeneity is discussed in terms of possible excited-state interactions in conjunction with the predicted secondary structure of CTnl. The loss of molecular asymmetry of cardiac troponin I induced by phosphorylation as demonstrated in this work may be related to the known physiological effect of beta-agonists on cardiac contractility. PMID- 1420939 TI - Dynamics of benzo[a]pyrene diol epoxide adducts in poly(dG-dC).(dG-dC) studied by synchrotron excited fluorescence polarization anisotropy decay. AB - Time-resolved fluorescence studies have been performed on (+)-anti-7,8 dihydrodiol-9,10-epoxybenzo[a]pyrene adducts in double-stranded poly(dG-dC).(dG dC). Part of the adduct population gives rise to excimer fluorescence. The heterogeneous fluorescence emission decay curves at 22 degrees C could be resolved into three components with lifetimes: 0.4 ns, 3 ns and 24 ns for the total fluorescence (monomer and excimer emission), and 0.5 ns, 5 ns and 24 ns, respectively, for excimer emission alone. The relative amplitudes for the longer lifetimes were larger for the pure excimer population than for the mixed population. The fluorescence polarization anisotropy decay curves were resolved into two components of rotational correlation times: 0.4 ns and 25 ns for the total fluorescence and 0.3 ns and 33 ns for the excimer fluorescence. We interpret the two rotational correlation times to correspond to local motion of the adduct and segmental motion of the polynucleotide, respectively. PMID- 1420940 TI - The vibrational normal modes of beta-barrels in an IgG antibody molecule. AB - Based on the quasi-continuity model, and using the method of group theory, we studied the normal vibrations of the VL- and the CHL-beta-barrels in an IgG molecule. We put emphasis on the Raman- and the infrared-active normal modes. The Raman modes we obtained include both the breathing motion mode (or the dominant low-frequency mode) which corresponds to the maximum peak in the Raman spectrum, and the normal modes that correspond to the lower peaks. Our calculated vibration frequencies are found to be in good agreement with the experimental results observed by Painter et al. (Biopolymers 20 (1981) 243). The method and work presented in this paper may improve Chou's quasi-continuity theory in calculating the vibrational modes of a beta-barrel protein. PMID- 1420941 TI - On the base sequences of the promoters in transcription initiation. AB - The base sequence of a specific DNA region identified as the promoter is investigated by means of the quantity S(r) corresponding to "superdelocalizability" of oxygen ion of each phosphate for the ten DNA dimer units ([XY/Y'X']2-) and ([XY/Y'X']2- + H+)-complexes. A mechanism is proposed of how RNA polymerase can recognize its transcription site (phosphate), and is applied to the Escherichia coli promoters, lacUV5, recAp, rrnEpl, and rrnEp2. The result explains fairly well the character of the promoters experimentally found. PMID- 1420942 TI - Thermal stability of proteins in intermolecular complexes. AB - A general phenomenological model is proposed for the estimation of the influence of the formation of complexes with ligands on thermal stability of proteins. In this model the reversible processes of unfolding-refolding and of association dissociation of protein-ligand complexes and of the irreversible chemical degradation of the unfolded protein were analyzed jointly. By using certain approximations, the analytical expressions for both the thermodynamic and kinetic stabilization are obtained. Two thermodynamic and four kinetic regimes of stabilization and destabilization can exist in such system. Each thermodynamic regime appears to be compatible with three different kinetic regimes. The effect of the formation of complexes on thermodynamic and kinetic stability of the protein is determined by the degrees of binding of the ligand to the folded and unfolded protein species and by the rates of irreversible degradation of free protein and protein in complex. PMID- 1420943 TI - Comments on the entropies of genetic codes of DNA and proteins. PMID- 1420944 TI - Generalization of the Spiegler-Kedem-Katchalsky frictional model equations of the transmembrane transport for multicomponent non-electrolyte solutions. AB - The Spiegler-Kedem-Katchalsky frictional model equations of the transmembrane transport for systems containing n-component, non-ionic solutions is presented. The frictional interpretation of the phenomenological coefficients of membrane and the expressions connecting the practical coefficients (Lp, sigma i, omega ij) with frictional coefficients (fij) are presented. PMID- 1420945 TI - Enhanced biopotency of synthetic C3a analogues by membrane binding. A fluorescence anisotropy decay study. AB - The biological activity of oligopeptide analogues of C3a is markedly increased by N-terminal attachment of a hydrophobic group as, for instance, 9 fluorenylmethoxycarbonyl (Fmoc), either direct or via a flexible 6-aminohexanoyl (Ahx) spacer. This study presents evidence from fluorescence anisotropy decay measurements that the hydrophobic appendix mediates non-specific binding of the synthetic peptide analogues to phospholipid vesicles. According to quantitative considerations no alternative or additional rate-enhancing mechanisms other than surface diffusion are required to account for the gain in biopotency. PMID- 1420946 TI - Time-resolved intrinsic fluorescence of Enzyme I. The monomer/dimer transition. AB - Enzyme I of the bacterial phosphotransferase system can exist in a monomer/dimer equilibrium which may have functional significance. Each monomer contains two tryptophan residues. It is demonstrated that the decay of both the monomer and the dimer can be described by a biexponential. The decay times depend on the temperature and at 6 degrees C the decay times are tau 1 = 0.4 ns and tau 2 = 3.2 ns for the monomer and tau 3 = 3.2 ns and tau 4 = 7.2 ns for the dimer form of the enzyme. The changes in the fluorescence decay parameters can be utilized to measure the equilibrium constant for the monomer/dimer transition. PMID- 1420947 TI - The self-association of human spectrin at high concentration. AB - The self-association of purified human spectrin has been studied at sedimentation equilibrium over a wide range of concentration (0-20 g/L) at 30 degrees C and pH 7.5. Coincidence of apparent weight average molecular weight and omega (r) plots as a function of total spectrin concentration indicated that equilibrium was attained and that no significant concentration of solute was incapable of participating in the self-association reaction. Under these conditions, no significant dissociation of the heterodimer to component polypeptide chains could be detected. The behavior of spectrin between 0 and 20 g/L can be described reasonably well by a cooperative isodesmic model, in which the protomer for association is the alpha beta heterodimer. With this model, the equilibrium constant for the heterodimer-tetramer step, K24, is 2 x 10(6) M-1, and K(iso), the equilibrium constant describing all other steps, is approximately 0.2 x 10(6) M-1. The returned value of the second virial coefficient for this model, 1.0 x 10(-7) L mol g-2, is consistent with the lower limit of values calculated for the heterodimer from the charge and Stokes radius of spectrin. On the other hand, the attenuated indefinite association model fails to describe the self-association of spectrin adequately over the range 0-20 g/L. Systematic decreases in the estimates of the second virial coefficient and the equilibrium constants for association beyond the tetramer suggest that the assumption of a single value of the second virial coefficient may not be appropriate for spectrin, and that non ideality would best be taken into account by consideration of the detailed solution composition. PMID- 1420948 TI - Effects of lipid structure on energy transfer from carbazolyl to anthryl groups in a lipid bilayer. AB - Two types of chromophoric amphiphiles were synthesized: one of them possesses a molecular structure of N,N-dialkyl aromatic amino acid (5X18 type, where X is A or Cz), and the other alpha,gamma-dialkylglutamate connected to aromatic amino acid (mXG12 type, where m is an integer). 5-N-Ethylcarbazolyl and 9-anthryl groups were chosen as the chromophore, and introduced to each amino acid derivative. All the amphiphiles formed assembly showing gel-liquid crystalline phase transition. The phase-transition temperature of the assembly composed of mXG12-type amphiphile was higher than that of 5X18-type amphiphile. Absorption and CD spectra of 6-(trimethylammonium)hexanoyl-L-3-(5-N-ethylcarbazolyl) alanine N,N-dioctadecylamide bromide (5Cz18) in the assembly indicated the absence of strong ground-state interactions between the carbazolyl groups, while those of 6 (trimethylammonium)hexanoyl-L-3-(5-N-ethylcarbazolyl)alanyl-L-gl utamic acid alpha,gamma-didodecyl ester (5CzG12) or 11-(trimethylammonium)undecanoyl-L-3-(5-N ethylcarbazolyl)al anyl-L-glutamic acid alpha,gamma-didodecyl ester (10CzG12) indicated the ground-state interactions based on dimer or higher aggregates. Fluorescence spectra of 5Cz18 showed very weak excimer emission, while excimer and/or excited dimer or higher aggregates were observed in the assembly of 5CzG12 or 10CzG12. Similar results were obtained for amphiphiles (mAG12) with anthryl and hydroxyethyldimethylammonium groups in places respectively of carbazolyl and trimethylammonium groups of 5CzG12 and 10CzG12. Taking these results together into consideration, the molecular packing of mXG12 in the assembly should be tighter than that of 5X18. In the binary assembly of 6 (trimethylammonium)hexanoyl-L-3-(9-anthryl) alanine N,N-dioctadecylamide bromide (5A18)/5Cz18 (1/99 mol/mol), about 60% of photoenergy absorbed by the carbazolyl groups was transferred to the anthryl groups, indicating an efficient energy migration along the two-dimensional array of carbazolyl chromophores of 5Cz18. On the other hand, in the mCzG12/mAG12 binary assembly, the energy-transfer efficiency was much lower due to the formation of dimer or the higher aggregates acting as energy-dissipating sites. PMID- 1420949 TI - Reduced lysozyme in solution and its interaction with non-ionic surfactants. AB - Reduced lysozyme at pH 2.5 bound poly(oxyethylene) alkylethers in two steps and the maximum bound amount Qmax of the surfactant reached as large as 0.5-0.7 mole per mole amino acid residue in the cooperative binding step. Binding isotherms were well superimposed when surfactant concentrations were normalized by respective values of the critical micelle concentration, cmc. In terms of the onset concentrations of the cooperative binding C*, hydrophobicity of reduced lysozyme was quantitatively defined as RT In (cmc/C*) which amounted to 670 J per mole surfactant and was unique to the protein irrespective of the kind of surfactant. Qmax could be used as another measure of the hydrophobicity of the protein. The binding isotherms were evaluated by two methods: equilibrium dialysis and surface tension. Their results were consistent with each other and rather complementary. Reduced lysozymes were molecularly dispersed at pH below 2.5 in 0.01 M NaCl but aggregation took place as pH increased. The aggregates could not be dissociated on dilution nor by the addition of nonionic surfactants but by lowering pH. The irreversible nature of the aggregation was reasonably interpreted with a model based on the 'entangled' arrangement of the beta-sheets, which could account for the irreversible aggregation of unfolded proteins in general. PMID- 1420950 TI - Chlorpromazine induced aggregation of normal human hemoglobin. Electron microscopic evidence. AB - Normal human hemoglobin exceeding a certain minimum concentration (called critical aggregation concentration) undergoes aggregation in presence of the psychotherapeutic drug chlorpromazine (CPZ). The critical aggregation concentration decreases with the increase of CPZ concentration. Electron micrographs of CPZ-treated hemoglobin clearly indicate that the aggregates of hemoglobin are in filamentous form of average width 75 +/- 8 A. A possible mechanism for such aggregation has been discussed. PMID- 1420952 TI - Nodules resembling arachnoid villi in pulmonary venules in plexogenic pulmonary arteriopathy. AB - We have found nodules histologically resembling arachnoid villi adjacent to pulmonary venules in a woman of 30 years with primary pulmonary hypertension. Such lesions have been reported previously in cases of mitral stenosis and pulmonary thromboembolism and we believe them to absorb excess water from the interstitial tissues of the alveolar walls, thus protecting the lung from the development of edema. In this way they seem to have a similar function to that of cerebral arachnoid villi and granulations which transport cerebrospinal fluid into the dural sinuses. PMID- 1420951 TI - Protective effect of selenium in cardiac ischemia and reperfusion. AB - The purpose of the present investigation was to establish whether pretreatment with selenium enhances the stores of selenium-dependent glutathione peroxidase in the tissues and to verify if and to what extent alterations of mechanical and biochemical cardiac properties induced by ischemia in the myocardium may be thus prevented. Ten rats had sodium selenite (6 micrograms/day) added to their drinking water for 4 weeks, while 10 control rats received no treatment. At the end of 4 weeks, the hearts were perfused by the Langendorff technique with oxygenated Krebs-Henseleit solution at a rate of 10 ml/min for 30 minutes at 37 degrees C. Ischemia was then induced by reducing the perfusion to 1 ml/min for 60 minutes; reperfusion followed at the control rate for a further 30 minutes. Isometrically developed pressure and its maximum first derivative at different ventricular volumes was measured before and after the ischemic period. Lactate and creatine kinase activity were measured in the effluent throughout. Tissue concentrations of adenine nucleotides and creatine phosphate and lutathione peroxidase activity were estimated after reperfusion. The rats treated with selenium showed a wide-spread increase in the activity of Se-dependent glutathione peroxidase in all tissues. There was an improved recovery of ventricular contraction during reperfusion and an increased myocardial content of adenine nucleotides and creatine phosphate. During reperfusion, the loss of creatine kinase into the perfusate was less in the treated animals, and there was a similar trend for the production of lactate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420953 TI - The effects of halothane, enflurane and isoflurane on the isolated rat heart recovering from cardioplegic arrest. AB - The direct cardiac effects of volatile anesthetics following cardioplegic ischemia were investigated in isolated, paced rat hearts. In one series of experiments, the hearts were perfused with oxygenated Krebs Henseleit solution for a 15-minute stabilization period and then the effect of the volatile anesthetic was tested. In another series of experiments, after the stabilization period, the hearts were subjected to cardioplegic (KCl 20mEq/L) ischemia at 30 degrees C for 30 minutes and then the effect of the volatile anesthetic was tested. Halothane, enflurane or isoflurane was introduced to the Krebs Henseleit solution at 0.7 and 1.4 minimal alveolar concentration. All the volatile anesthetics decreased myocardial contractility in a dose dependent manner both before and after cardioplegic arrest. Halothane decreased coronary flow, while isoflurane and enflurane increased coronary flow in both the cardioplegic and non cardioplegic hearts. The influence of the anesthetics was transient and ceased once they were withdrawn. Ischemic cardioplegia did not affect the response to volatile anesthetics. PMID- 1420954 TI - The effects of L-arginine mono(2-mercaptoethanesulfonate) on the ischemic and reperfused heart. AB - We evaluated the effectiveness of L-arginine mono(2-mercaptoethanesulfonate) (argimesna) to limit the extent of myocardial damage resulting from 60 minutes of severe ischemia followed by 30 minutes of reperfusion in the Langendorff-perfused rabbit heart. Argimesna is a sulfhydryl group containing molecule which has no effect on glutathione status or on the total thiol pool. The effects of 10(-6) M argimesna were compared with those of 10(-6) M L-arginine and of 10(-6) M sodium salt of 2-mercaptoethanesulfonate (mesna). Pretreatment of the hearts with 10(-6) M argimesna resulted in marked myocardial protection, measured in terms of improved recovery of developed pressure (p less than 0.01), reduced release of creatine kinase (p less than 0.01), maintenance of mitochondrial function and increased stores of ATP on reperfusion (p less than 0.01). On reperfusion less oxidative stress developed, as indicated by less accumulation of oxidized glutathione (p less than 0.01). These effects were specific for argimesna; no significant protection could be found for mesna and L-arginine. The beneficial effects of argimesna could not be explained by hemodynamic differences or effects on anaerobic metabolism. Neither is it likely that argimesna acts as a free radical scavenger at the concentrations employed. The protection may be achieved by maintenance of -SH groups during ischemia and reperfusion. PMID- 1420955 TI - Cardiac ATP breakdown and mechanical function during recurrent periods of anoxia. AB - The effect of repeated short anoxic or ischemic periods on ATP breakdown and cardiac function remains controversial. To analyze this issue further and to study the regulation of adenine nucleotide breakdown during recurrent cardiac anoxia, we compared two different protocols of intermittent anoxia. Four rat hearts, perfused according to Langendorff, were exposed to 12 periods of anoxia, each lasting 1 minute, with reoxygenation periods of 3 minutes (protocol A). A second group of 8 hearts were made anoxic for 6 periods of anoxia, each lasting 1 minute, followed by 6 periods of anoxia, each lasting 2 minutes, with the same reoxygenation periods (protocol B). Adenosine production was studied with high performance liquid chromatography, ventricular contraction was monitored using a force transducer. During anoxia a substantial vasodilation and immediate fall in strength of ventricular contraction occurred. They were most pronounced during the first anoxic period and during the change from 1 to 2 minute periods of anoxia. Adenosine production was about 1 nmol/min during the first 1-minute anoxic period, decreasing during the following 1-minute anoxic periods. During the first 2-minute anoxic period, a new and much higher adenosine peak was observed (6 nmol/min), decreasing during the following 2-minute anoxic periods. Total purine release followed a pattern similar to that of adenosine. The concentration of ATP at the end of protocol B was 18.5 mumol/g dry tissue, which is significantly lower than that in protocol A (21.6 mumol/g). The results show that ATP breakdown during intermittent anoxia gradually decreases, notwithstanding the presence of substantial amounts of ATP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420956 TI - Effect of magnesium on myocardial damage induced by epinephrine. Ultrastructural and cytochemical study. AB - Magnesium ion is involved in energy metabolism, transport of ions and control of intracellular Ca2+. Catecholamines, intensify cellular Mg2+ depletion and the detrimental effects of catecholamine excess and Mg2+ deficiency are mutually enhancing in the myocardium. To investigate whether Mg2+ supplementation protects the myocardium against damage induced by catecholamines, we examined the ultrastructure and the ultracytochemical localization of Ca2+ in the myocardium of rabbits infused with epinephrine (1 microgram/kg/min intravenously for 2 hours), in rabbits infused simultaneously with epinephrine and MgSO4 (50 mg/kg, intravenously) and in saline-infused controls. Qualitative evaluation showed that Mg2+ supplementation attenuated the mitochondrial alterations induced by epinephrine and decreased intracellular and endothelial swelling. Ultracytochemistry with oxalate-pyroantimonate showed a shift in the localization of Ca2+ from the vicinity of the sarcolemma in the controls into the mitochondria in epinephrine-treated hearts. Mg2+ supplementation had no effect on the changes in Ca2+ localization induced by epinephrine or on the intensity of the cytochemical reaction. In conclusion, Mg2+ supplementation reduces the ultrastructural features of myocardial damage induced by epinephrine without an effect upon changes in intracellular distribution of Ca2+ induced by epinephrine, as shown cytochemically. PMID- 1420957 TI - Design of peptides: synthesis, crystal structure, molecular conformation, and conformational calculations of N-Boc-L-Phe-Dehydro-Ala-OCH3. AB - It is noteworthy that the dehydro-Ala residue adopts an extended conformation that is different than those observed in dehydro-Phe, dehydro-Leu, and dehydro Abu. The peptide N-Boc-L-Phe-dehydro-Ala-OCH3 (C18H24N2O5) was synthesized by the usual workup procedure and finally by converting N-Boc-L-Phe-L-Ser-OCH3 to N-Boc L-Phe-dehydro-Ala- OCH3. It was crystallized from its solution in a methanol water mixture at room temperature. The crystals belong to the monoclonic space group P2(1), with a = 9.577(1) A, b = 5.195(3) A, c = 19.563(3) A, beta = 94.67(5) degrees, V = 970.1(6) A3, Z = 2, dm = 1.201(5) Mg m-3, dc = 1.197(5) Mg m-3. The structure was determined using direct method procedures. It was refined by a full-matrix least-squares procedure to an R value of 0.048 for 1370 observed reflections. The C2 alpha-C2 beta distance is 1.327(8) A, while the bond angles N2-C2 alpha-C2' and C1'-N2-C2 alpha are 109.8(5) degrees and 127.8(5) degrees, respectively. The backbone adopts a nonspecific conformation with dehydro-Ala in a fully extended conformation with the following torsion angles: theta 1 = 175.2(4) degrees, omega 0 = 170.2(4) degrees, phi 1 = 135.8(5) degrees, psi 1 = 22.6(6) degrees, omega 1 = 168.5(5) degrees, phi 2 = -170.3(5) degrees, psi 2T = 178.6(5) degrees, theta T = 178.4(7) degrees. The rigid planar and trans conformation of dehydro-Ala forces Phe to adopt a strained conformation. The Boc group has a trans-trans conformation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420958 TI - Combined use of homo- and heteronuclear coupling constants as restraints in molecular dynamics simulations. AB - A penalty function for scalar coupling constants has been applied in molecular dynamics simulations as an experimental constraint. The function is based on the difference between the coupling constant calculated from the dihedral angle and the experimentally measured coupling constant. The method is illustrated on a model cyclic pentapeptide for which 3JHN-H alpha and 3JHN-C beta, both about the phi backbone dihedral angle, have been measured. The function is efficient in producing structures consistent with the scalar couplings, but removed from the conformation observed in solution. This arises from the lack of J restraints for the psi dihedral angle. Simulations with both nuclear Overhauser effect (NOE) and J-coupling restraints illustrates small but significant differences from simulations using only NOEs. PMID- 1420959 TI - Molecular dynamics conformational search of six cyclic peptides used in the template assembled synthetic protein approach for protein de novo design. AB - Six cyclic peptides, designed to act as topological templates in the TASP (template assembled synthetic protein) approach in protein de novo design, were investigated employing a 100-ps, 900-K molecular dynamics conformational search. The peptides are composed of two Lys-X-Lys (X = Gly, Ala) tripeptides connected at its N- and C-terminal end by a Pro-Gly motif and a cystine bridge (I), two Pro Gly units (II), naphthalene derivatives (III), and tetrahydronaphthalene derivatives of different stereochemistry (IV-VI). The molecular dynamics conformational search established that template I had beta-sheet like geometry. Templates II-VI showed different preferential geometries, among them, e.g., distinct preferences for type V turns in Pro-Gly containing peptides and close spatial arrangement of hydrophobic naphthalene moieties. The orientation of the lysine side chains within preferential geometries of the individual templates is analyzed and a tentative evaluation for their potential to stabilize TASP molecules of 4-helix bundle topology is given. PMID- 1420960 TI - The spectroscopic properties of the lipodepsipeptide, syringomycin E. AB - The spectroscopic properties of syringomycin E, an antibiotic lipodepsinonapeptide associated with pathological states in plants, have been investigated by uv absorbance and CD spectroscopies, and by the synthesis of relevant model compounds. Initial studies [E. Vaillo, A. Ballio, P. L. Luisi, and R. M. Thomas (1990) in Peptides 1990, Giralt, E. & Andreu, D., Eds., Escom Scientific, Leiden, Netherlands] suggested that a significant contribution to the spectra was due to the presence of a zdehydroaminobutyric acid residue in the amino acid sequence. The model peptides N-Boc-L-Phe-delta zAbu-OMe and its analogue, N-Boc-L-Phe-L-Thr-OMe, lacking the unsaturated bond, were synthesized using standard solution chemistry, and a detailed investigation was made in which the spectra of the models and that of syringotoxin (an antibiotic closely related to syringomycin E but without a Phe residue) were compared with those of syringomycin E under a variety of solvent conditions. The uv absorbance spectra of both N-Boc-L-Phe-delta zAbu-OMe and syringomycin E clearly showed the presence of the unsaturated residue while the CD spectra were complex, environmentally sensitive, and contained contributions from both the delta zAbu and Phe residues. In the course of these studies extinction coefficients were obtained for syringomycin E and its dipeptide model. The origins of the uv and CD spectra are discussed in detail, and a comparison is made with the spectra of other, similar lipopeptide antibiotics. Finally, a structural model for syringomycin is proposed in which the changes induced in the spectrum by alterations in the solvent environment are accommodated. PMID- 1420961 TI - Variable ranges of interactions in polypeptide conformations with a method to complement molecular modeling. AB - Formulations of conformational weights for helix-coil transitions can be extended to substantially more complex situations than are usually pursued. General rules for matrix multiplication that depend parametrically on the interaction ranges and numbers of rotamers of residues are presented. The orders of the matrices of statistical weights can be increased with chain length, so that an individual matrix element can represent any specified single conformation, as needed. By the appropriate choice of interaction ranges and numbers of available conformers, approximations can be introduced in which: (1) an average of the conformations of any chain segment is obtained, (2) specific residue-residue interactions are excluded, or (3) the conformation of a part of the chain is restricted or fixed. The method is appropriate for treating specific interactions in peptides and could be used together with available experimental information to develop models of conformational transitions. As such, the methods represent a class of calculations aimed at more rigorous calculations built around known features of a molecule. The aim is to facilitate calculations that bridge the gap between nonquantitative molecular model building and more rigorous but less directed molecular mechanics calculations. The method can directly include any desired longer range of interactions, if the interaction range is not too long to make impossible the manipulation of the requisite matrices. An outline is presented of an application to treat salt bridges in the C peptide of ribonuclease A. PMID- 1420963 TI - Stacking interactions of ApA analogues with modified backbones. AB - CD spectra have been measured as a function of temperature for a number of ApA analogues with modified backbones. Oligonucleotides with these modified backbones are being used as antisense agents having potential as viral therapeutics. Results of these studies show that when a carbonyl is substituted for the phosphate to produce an uncharged backbone, the analogues that have either sugar or morpholino substitution do not stack. In contrast, when a morpholino group is substituted for the sugar and the phosphate is modified so as to be uncharged, there is strong base stacking. Stacking interactions in the phosphorus-linked morpholino analogues are at least as strong as those found in d(ApA). The stacking interactions in ApA are weak by comparison. Singular value decomposition demonstrates that the stacking is two state, and Taylor series decomposition yields a coefficient that measures base stacking interactions. The van't Hoff equation is applied to the base stacking coefficient from the Taylor series fitting to give thermodynamic parameters. PMID- 1420964 TI - Excluded volume effects on the partition of single- and double-stranded oligodeoxynucleotides between two liquid phases. AB - The distribution coefficients of single- and double-stranded oligodeoxynucleotides in a PEG 8000/phosphate two-phase system are a function of their chain length. Values of the distribution coefficients are in general agreement with a simple extension of a model for excluded volume effects (the "available volume model") which was applied previously to the distribution of proteins in this system. The current results therefore provide a second set of examples for molecules of very different geometry where the distribution added molecules is controlled by excluded volume interactions between those molecules and the PEG 8000 of the two-phase system. PMID- 1420962 TI - Interpretation of 25Mg spin relaxation in Mg-DNA solutions: temperature variation and chemical exchange effects. AB - The temperature dependencies of line shapes and spin-lattice relaxation times T1 have been measured for 25Mg in dilute solutions of Na-DNA/NaCl containing varying amounts of added magnesium(II) ions. The 25Mg spectrum is clearly non-Lorentzian, due to the presence of motions modulating the quadrupolar interaction that are slow compared to the inverse of the Larmor frequency. The weakly temperature dependent line shapes and relaxation rates appear to be influenced by the relatively slow exchange of the Mg2+ ions between the DNA surface and the aqueous bulk phase. The observed temperature dependencies depend on the ratio of total magnesium to DNA phosphate, Mg/P. The line shape as well as the temperature dependence of the line width at half height can be qualitatively reproduced with a two-site discrete exchange model for the quadrupolar relaxation of a spin 5/2 nucleus in isotropic solution. The calculations give a value of the lifetime for magnesium bound to DNA of 4 ms at room temperature. Previously reported temperature-dependent 43Ca relaxation measurements in DNA solution can be reproduced under the assumption of a mean lifetime of bound calcium that is not larger than 2 ms but not smaller than 50 microseconds at room temperature. The temperature variation of T1 for 25Mg has been calculated, giving some qualitative agreement with the data. The correlation time for bound 25Mg has been found to be about 40 ns at room temperature. PMID- 1420965 TI - A molecular thermodynamic approach to predict the secondary structure of homopolypeptides in aqueous systems. AB - Under physiological conditions, many polypeptide chains spontaneously fold into discrete and tightly packed three-dimensional structures. The folded polypeptide chain conformation is believed to represent a minimum Gibbs energy of the system, governed by the weak interactions that operate between the amino acid residues and between the residues and the solvent. A semiempirical molecular thermodynamic model is proposed to represent the Gibbs energy of folding of aqueous homopolypeptide systems. The model takes into consideration both the entropy contribution and the enthalpy contribution of folding homopolypeptide chains in aqueous solutions. The entropy contribution is derived from the Flory-Huggins expression for the entropy of mixing. It accounts for the entropy loss in folding a random-coiled polypeptide chain into a specific polypeptide conformation. The enthalpy contribution is derived from a molecular segment-based Non-Random Two Liquid (NRTL) local composition model [H. Renon and J. M. Prausnitz (1968) AIChE J., Vol. 14, pp. 135-142; C.-C. Chen and L. B. Evans (1986) AIChE J., Vol. 32, pp. 444-454], which takes into consideration of the residue-residue, residue solvent, and solvent-solvent binary physical interactions along with the local compositions of amino acid residues in aqueous homopolypeptides. The UNIFAC group contribution method [A. Fredenslund, R. L. Jones, and J. M. Prausnitz (1975) AIChE J., 21, 1086-1099; A. Fredenslund, J. Gmehling, and P. Rasmussen (1977) Vapor-Liquid Equilibrium Using UNIFAC, Elsevier Scientific Publishing Company, Amsterdam], developed originally to estimate the excess Gibbs energy of solutions of small molecules, was used to estimate the NRTL binary interaction parameters. The model yields a hydrophobicity scale for the 20 amino acid side chains, which compares favorably with established scales [Y. Nozaki and C. Tanford (1971) Journal of Biological Chemistry, Vol. 46, pp. 2211-2217; E. B. Leodidis and T. A. Hatton (1990) Journal of Physical Chemistry, Vol. 94, pp. 6411-6420]. In addition, the model generates qualitatively correct thermodynamic constants and it accurately predicts thermodynamically favorable folding of a number of aqueous homopolypeptides from random-coiled states into alpha-helices. The model further facilitates estimation of the Zimm-Bragg helix growth parameter s and the nucleation parameter sigma for amino acid residues [B. H. Zimm and J. K. Bragg (1959) Journal of Chemical Physics, Vol. 31, pp. 526-535]. The calculated values of the two parameters fall into the ranges suggested by Zimm and Bragg. PMID- 1420966 TI - Analyzing the normal mode dynamics of macromolecules by the component synthesis method. AB - This paper presents a general method for studying the harmonic dynamics of large biomolecules and molecular complexes. The performance and accuracy of the method applied to a number of molecules are also reported. The basic approach of the method is to divide a macromolecule into a number of smaller components. The local normal modes of the components are first calculated by treating individual components and the interactions between nearest neighboring components. The physical displacements of all atoms are then represented in the local normal mode space, in which a selected range of high-frequency local modes is neglected. The equation of motion of the molecule in the local normal mode space will then have a smaller dimension, and consequently the normal modes of the whole structure, particularly for large molecules, can be solved much more easily. The normal modes of two polypeptides--(Ala)6 and (Ala)12--and a double-helical DNA- d(ATATA).d(TATAT)--are analyzed with this method. Reductions on the dimensions of harmonic dynamic equations for these molecules have been made, with the fraction of the deleted high-frequency modes ranging from 1/2 to 5/6. The calculated low frequency normal modes are found to be very accurate as compared to the exact solutions by standard procedure. The major advantage of the present approach on macromolecule harmonic dynamics is that the reduction on the dimensionality of the eigenvalue problems can be varied according to the size of molecules, so the method can be easily applied to large macromolecules with controlled accuracy. PMID- 1420967 TI - Resolution of the electronic absorption spectra of the adenine and thymine residues in poly(dA).poly(dT). PMID- 1420968 TI - Terbium(III)-induced fluorescence of four-stranded G4-DNA. PMID- 1420969 TI - Discontinuous volume transitions in ionic gels and their possible involvement in the nerve excitation process. AB - Discontinuous volume changes in polymer gels carrying negatively ionized groups were studied by varying the molarities of univalent and bivalent cations in the bathing solution. These studies offer a sound basis for elucidating the origin of rapid swelling and heat production in nerve fibers associated with the process of excitation. PMID- 1420970 TI - Vibrational studies of the disulfide group in proteins. VI. General correlations of SS and CS stretch frequencies with disulfide bridge geometry. AB - Normal mode calculations have been done on a range of disulfide bridge conformations in order to determine how the SS stretch and CS stretch frequencies depend on structure. In addition to varying the C alpha C beta SS and NC alpha C beta S dihedral angles, we have varied the phi, psi of the adjoining peptide groups since we have shown that these also influence the above frequencies. In order to obtain structural information from the observed frequencies, we have done a study of the conformational states found in 92 disulfide bridges in 25 known protein structures. This permits making a statistically based correlation between CS stretch frequencies and the possible contributing conformers. PMID- 1420971 TI - A molecular dynamics study of conformational changes and hydration of left-handed d(CGCGCGCGCGCG)2 in a nonsalt solution. AB - Twelve dinucleotides (one complete turn) of left-handed, flexible, double-helix poly(dG-dC) Z-DNA have been simulated in aqueous solution with K+ counterions for 70 ps. Most of the d(GpC) phosphates have rotated in accordance with a ZI----ZII transition. The ZII conformation was probably partly stabilized by counterions, which coordinate one of the anionic oxygens and the guanine-N7 of the next (5'--- 3' direction) base. The presence of base-coordinating ions close to the helical axis rotated and pulled about half of the d(CpG) phosphates further into the groove. These ions also gave rise to rather large deviations from the crystal structure (ZI) with their tendency of pulling the bases closer toward the helical axis. A flipping of the orientation about the glycosyl bond from the +sc to the sc region was observed for one guanosine, also leading to deviations from the crystal structure. Many bridges containing one or two water molecules were found, with a dominance for the latter. They essentially formed a network of intra- and interstrand bridges between anionic and esterified phosphate oxygens. A "spine" of water molecules could be distinguished as a dark zig-zag pattern in the water density map. The lifetime of a bridge containing one water was about twice as long as that of a two-water bridge and it lasted 5-15 times longer than a hydrogen bond in water. The lifetimes were also calculated for a selection of bridge types, in order of decreasing stability: O1P/O2P ... W ... O'4 much greater than O1P/O2P ... W ... guanine-N2 greater than O1P/O2P ... W ... O1P/O2P. The reorientational motion of water molecules in the first hydration shell around selected groups was slowed down considerably compared to bulk water and the decreasing order of correlation times was guanine-N2 greater than O'4 greater than O'3/O'5 greater than O1P/O2P. PMID- 1420972 TI - The use of UV-visible spectroscopy for the determination of hydrophobic interactions between neuropeptides and membrane model systems. AB - Ultraviolet-visible spectroscopy has been used as a rapid method to evaluate the hydrophobic interactions between a series of cationic and zwitterionic neuropeptides and dipeptides with the hydrophobic core of two membrane model systems; sodium dodecyl sulfate and lysophosphatidylcholine micelles. If a hydrophobic interaction occurs, a 1-nm bathochromic shift is observed in the uv visible spectrum of the aromatic side chains when going from aqueous solution to a micellar solution. The aromatic residues of substance P, bradykinin, and Des Arg9 bradykinin all exhibited the 1-nm bathochromic shift in the presence of sodium dodecyl sulfate while those of Met-enkephalin did not. The opposite effects were observed in the presence of lysophosphatidylcholine micelles. PMID- 1420973 TI - DNA flexibility as a function of allomorphic conformation and of base sequence. AB - Systematic theoretical modeling of symmetric DNA oligomers, carried out earlier for the B conformation, is now extended to A-DNA. In contrast to the previous results, it is found that A-DNA shows no multiplicity of low-energy substate conformations. The possibilities of the Jumna algorithm are subsequently applied to studying deformations of the oligomers. Controlled winding and stretching deformations are used to study how the two allomorphs and different base sequences absorb such external stress. The results help explain the internal mechanics of the DNA double helix and the extent to which fine structure influences this behavior. The results point to some differences between the A and B double helices, but also to many similarities. Sequence effects on flexibility are relatively limited compared to their impact on optimal energy conformations. It is also shown that the conformational substates detected for B-DNA oligomers are preserved under deformation, but have little influence on its energetics. PMID- 1420974 TI - Salt-dependent stability of poly(dG).poly(dC) with potential of mean force Coulomb interactions. PMID- 1420975 TI - Electrostatic forces in two lysozymes: calculations and measurements of histidine pKa values. AB - In order to examine the electrostatic forces in globular proteins, pKa values and their ionic strength dependence of His residues of hen egg white lysozyme (HEWL) and human lysozyme (HUML) were measured, and they were compared with those calculated numerically. pKa values of His residues in HEWL, HUML, and short oligopeptides were determined from chemical shift changes of His side chains by 1H-nmr measurements. The associated changes in pKa values in HEWL and HUML were calculated by solving the Poisson-Boltzmann equations numerically for macroscopic dielectric models. The calculated pKa changes and their ionic strength dependence agreed fairly well with the observed ones. The contribution from each residue of each alpha-helix dipole to the pKa values and their ionic strength dependence was analyzed using Green's reciprocity theorem. The results indicate that (1) the pKa of His residues are largely affected by surrounding ionized and polar groups; (2) the ionic strength dependence of the pKa values is determined by the overall charge distributions and their accessibilities to solvent; and (3) alpha-helix dipoles make a significant contribution to the pKa, when the His residue is close to the helix terminus and not fully exposed to the solvent. PMID- 1420976 TI - Elongational flow studies on DNA in aqueous solution and stress-induced scission of the double helix. AB - Elongational flow techniques are used to investigate the birefringent response and flow-induced molecular scission of monodisperse phage-DNA samples in aqueous solution. A 4-roll mill apparatus was used to characterize the solutions at low stain rates, epsilon less than or equal to 300 s-1, and the opposed jets apparatus used to study fracture of the DNA molecules at strain rates up to 15 x 10(3) s-1. The molecular weight values were measured before and after fracture in elongational flow using the high-resolution technique of pulsed field gel electrophoresis (PFGE). The birefringent response incorporates both rigid and flexible components. The birefringence is nonlocalized and rises gradually to a plateau value, similar to rigid-rod behavior. In addition a certain minimum value in the strain rate is necessary, an onset value epsilon 0, before the signal appears, indicating a flexible component. This behavior is consistent with a hinged-rod model and is similar to that observed for the protein collagen molecule at elevated temperature. We propose that this type of behavior is likely for multistrand rope-like macromolecules where localized separation or partial untwisting of the intertwined chains occurs, creating temporary hinges, in accordance with biochemical evidence for sequence-specific sites of flexibility. Results are presented on the entanglement effects at high concentrations. We have calculated rotational diffusion rates as a function of concentration and molecular weight. Using PFGE to measure the molecular weight profiles, our fracture studies at high strain rates demonstrate chain halving and quartering in accordance with the predictions of the thermally activated barrier to scission theory for single-chain polymers. PMID- 1420977 TI - Origins and consequences of ligand-induced multiphasic thermal protein denaturation. AB - The presence of subsaturating levels of a high-affinity ligand has been demonstrated both by experiment and calculation to have far-reaching consequences on thermally induced protein denaturation due to the coupling between the protein denaturation and ligand-binding equilibria. Under such circumstances, a protein may undergo biphasic denaturation even though in the absence of ligand it exhibits a thermogram comprised of a single essentially symmetric endotherm. Up to now, the presence of just 2 maxima in the thermogram has been presented merely as an experimental observation or as the result of equilibrium computations. Here we develop a thermodynamic description of the linkage between these equilibria in which the number of cusps present in the thermogram correlates with the number of resolved steps in the plot of saturation level of remaining native protein vs temperature (i.e., the thermal binding curve). During thermally induced denaturation, the concentration of native protein decreases; thus, the native protein in effect is titrated with ligand at constant total ligand concentration. The free ligand concentration The free ligand concentration increases substantially through the release of bound ligand by unfolding protein thereby increasing the saturation level of the remaining native protein. The form of this thermal binding curve is a function of the number of ligand-binding sites on the protein, the magnitudes of the association constants, and the total ligand and total protein concentrations. As a result, the model predicts multiphasic denaturation of a single cooperative unit when the thermal binding curve consists of discrete multiple steps. The presence of only 2 maxima (i.e., a single cusp) in a thermogram for a protein with multiple sites on the native species derives from the form of the thermal binding curve, which in this case is a single-step sigmoidal plot, and not from the predominant denaturation of unliganded and fully liganded native species. In addition, it is shown that, in general, the contributions from the denaturation of individual native protein species are decidedly non-two-state in character; thus, simple deconvolution should not be carried out. The effects of nonzero values of delta Cp and d delta Cp/dT for denaturation and of changes in enthalpy and in heat capacity for ligand binding, as well as the interaction of ligand with the denatured protein, are explored also. PMID- 1420978 TI - Thermodynamic substantiation of water-bridged collagen structure. AB - A solution of the problem of topology of a hydrogen bond net in a triple helix of collagen is suggested on the basis of an analysis of thermodynamic data on denaturation of phylogenetically different collagen [T. V. Burjanadze (1982), Vol. 21, pp. 1489-1501; T. V. Burjanadze, E. I. Tiktopulo, and P. L. Privalov (1987), Dokl. Akad. Nauk. USSR, Vol. 293, pp. 720-724] as well as on the earlier evaluation of the energy of the OH group of the 4-hydroxyproline bond [A. R. Ward and P. Mason (1973), Journal of Molecular Biology, Vol. 29, pp. 431-435]. It is shown that only the water-bridged collagen structure [G. N. Ramachandran and R. Chandrasekharan (1968), Biopolymers, Vol. 6, pp. 1649-1661; G. N. Ramachandran, M. Bansal, and R. S. Bhatnagar (1973), Biochimica Biophysica Acta, Vol. 322, pp. 166-171; M. Bansal, C. Ramakrishnan, and G. N. Ramachandran (1975), Proceedings of the Indian Academy of Sciences, Vol. 82, pp. 152-164] can explain both the change of thermostability upon proline hydroxylation [J. Rosenbloom, M. Harsch, and S. Jimenez (1973), Archives of Biochemistry and Biophysics, Vol. 158, pp. 478 484] and its phylogenetic change [T. V. Burjanadze (1982)]. PMID- 1420979 TI - Presence of a thermostable domain in the helical part of the type I collagen molecule and its role in the mechanism of triple helix folding. AB - A study has been done of the effect of neutral salts (NaCl and CaCl2) on the mechanism of type I collagen triple helix folding and unfolding in concentrated acetic acid solutions (2-8.8 M). It is shown that in these conditions, thermoabsorption and secondary structure change in heated solutions proceed in two consecutive stages. Salts exert a different destabilizing effect on different sites of the macromolecule, promoting the detection of a thermostable domain. The presence of a thermostable domain permits one to carry out reversible denaturation of collagen and to study the mechanism of the triple helix folding. Proceeding from the mechanism of the triple helix folding, an assumption has been made on the localization of the thermostable domain and its biological role. PMID- 1420980 TI - Synthesis of new hydrophilic microspheres: optimized carriers for microparticle enhanced nephelometric immunoassays. AB - To optimize antigen-antibody reactions, we have synthesized chemically well defined hydrophilic microspheres. Proteins or haptens were covalently linked to these carriers. When the microsphere conjugates were agglutinated by the corresponding antiserum, the size of the complex artificially increased during the immunological reaction. After optimizing various parameters such as the hydrophilic character, repulsion charges, and amount of antigen coupled to the microspheres, we developed a rapid and sensitive immunoassay based on laser light scattering by the complexes. PMID- 1420981 TI - Conformational studies of anionic melittin analogues: effect of peptide concentration, pH, ionic strength, and temperature--models for protein folding and halophilic proteins. AB - Melittin (MLT), a 26-residue cationic (net charge +5 at pH 7.2) peptide from bee venom, is well known to be a monomeric, approximately random coil; but when its charges are reduced by titration, by acetylation (net charge +2) or succinylation (net charge -2), or by screening by salt, it goes over to tetrameric alpha-helix. The conversion is promoted by raising the peptide concentration. The tetramer is held together by hydrophobic forces. We have changed the net charge to -6 by acylation with acetylcitric anhydride (a new acylating agent); this anionic derivative forms tetrameric helix at neutral pH, without salt, and at relatively low concentration, conditions under which the cationic MLT does not become helical. Thus, a high net charge is not sufficient to prevent association and helix formation. We have synthesized an anionic melittin analogue of MLT (E-MLT; net charge -4) in which all five lysine and arginine residues are replaced with glutamate, and acetyl and succinyl derivatives of E-MLT (net charges -5 and -6). All three of these are resistant to helix formation. They require much higher NaCl or NaClO4 concentration for helix formation than does MLT. Even CaCl2, MgCl2, and spermine.4HCl are less effective in helicizing E-MLT than MLT. MLT, at pH 7.2, shows increasing helix as the peptide concentration increases (8-120 microM), but E-MLT and its acyl derivatives do not. MLT and acylated MLTs in the helical tetramer show both cold- and heat-induced unfolding, with maximum stability near room temperature. At high temperature, a significant amount of residual structure remains. Heating (to 100 degrees C) monomeric MLT (i.e., MLT at low concentration) or E-MLT results in a monotonic increase in negative ellipticity. In 1.0 M NaCl, E-MLT (at sufficiently high concentration) also shows cold and hot unfolding. The results are discussed in respect to charge-charge and charge-dipole interactions, and hydrophobic effects. E-MLT is also discussed in relation to proteins of halophilic bacteria, which have higher proportions of anionic residues than do corresponding proteins of nonhalophiles. PMID- 1420982 TI - Conformational and ion binding properties of a cyclic octapeptide, cyclo (Ala-Leu Pro-Gly)2. AB - The conformation and ion-binding characteristics of a cyclic octapeptide, cyclo (Ala-Leu-Pro-Gly)2, in a liphophilic solvent, acetonitrile, have been studied using CD and nmr spectroscopy. The peptide binds preferentially to divalent cations such as calcium, magnesium, and barium. The conformations of the free cyclic peptide and its calcium complex are very similar with well-defined beta- and gamma-turns. The cyclic peptide readily forms equimolar and possibly 2:1 (peptide:cation) complexes with divalent cations. PMID- 1420983 TI - The electrostatic potential for the phosphodiester group determined from X-ray diffraction. AB - The charge density distribution in the crystal structure of ammonium dimethylphosphate at 123 K has been determined from x-ray diffraction data (MoK alpha) using 8437 reflections with sin theta/lambda less than 1.33 A-1 [NH4+.(CH3)2PO4-, M(r) = 143.08, monoclinic, P2(1)/c, a = 10.007(1), b = 6.926(1), c = 9.599(2) A, beta = 105.40(1) degrees, V = 641.4(3) A3, Z = 4, F000 = 304, Dx = 1.4815 g.cm-3, mu = 3.726 cm-1]. Least-squares structure refinement assuming Stewart's rigid pseudoatom model (variables including Slater-type radial exponents and electron populations for multipole terms extending to octapoles for C, N, O, and P, and dipoles for H) gave R(F2) = 0.039 for all reflections. The dimethylphosphate anion is in the gauche-gauche conformation and has approximate twofold symmetry. One phosphoryl O atom forms three hydrogen bonds and the other forms one. Neither of the ester O atoms is hydrogen bonded. For the dimethylphosphate anion isolated from the crystal structure, a map of the electrostatic potential obtained using the pseudoatom charge parameters shows that the phosphoryl O atoms are considerably more electronegative than the ester O atoms. The electrostatic potential distribution obtained in this way has been fitted by least squares to a system of atom-centered point charges. The potential calculated from these point charges agrees with the experimental result. It also agrees reasonably well with potentials obtained from three other systems of point charges that are widely used as part of the semiempirical force field for molecular mechanics and molecular dynamics calculations involving nucleic acids. PMID- 1420984 TI - Conformation of diastereomeric peptide sequences: structural analysis of Z-D-Val Ac6c-Gly-L-Phe-OMe. AB - We have recently undertaken a systematic structural analysis of fully protected tetrapeptides containing at the N- and C-terminus either homo- or heterochiral amino acids, spaced by an achiral dipeptide segment. The interest for this class of peptides derives from the observation that, on reverse-phase (HPLC), the homo- and heterochiral sequences have a markedly different retention times. The diastereomeric sequences, namely Z-(L/D)-Val-X-Y-L-Phe-OMe (X = Sar, Gly, Ac3c, Aib, Ac5c, Ac6c, Deg, Dpg, Dbu, Dip, Dph; Y = Sar, Gly, Ac3c, Aib, Ac5c, Ac6c) show different overall hydrophobicity attributed to a different three-dimensional structure that also depends on the X-Y segment. Therefore, following preliminary studies in solution, we report here the detailed x-ray analysis of the tetrapeptide Z-D-Val-Ac6c-Gly-L-Phe-OMe in order to understand the structural features governing the overall hydrophobicity of linear fully protected tetrapeptides. PMID- 1420985 TI - Conformations in solution of angiotensin II, and its 1-7 and 1-6 fragments. AB - High-resolution proton spectra at 620 MHz of human angiotensin II (1-8), angiotensin II (1-7), and angiotensin II (1-6) have been obtained in aqueous solution at acidic pH, and in dimethylsulfoxide solution. Complete chemical shift assignments for all three angiotensin peptides were made based on two-dimensional (2D) correlated spectroscopy and 2D-CA-MELSPIN spectra. Based on the measured values of 3JHNCH, the pattern of observed transverse Overhauser effects, and side chain coupling constants, it is concluded that all three analogues exist in H2O or DMSO-d6 as a mixture of conformers that is largely extended, with negligible content of folded structures, such as beta-turns, gamma-turns, or helix content. The results fit well with those of Nikiforovich et al. PMID- 1420986 TI - Alpha-elastin coacervate as a protein liquid membrane: effect of pH on transmembrane potential responses. AB - A protein liquid membrane composed of coacervated alpha-elastin, a chemical fragmentation product of the biological elastic fiber protein, functioned as an amphoteric liquid ion-exchange membrane. Ionic permselectivities of the alpha elastin coacervate membrane to a series of metal chlorides were investigated for the concentration-cell systems by the ordinary electrochemical measurements. Effects of pH on the transmembrane potential responses for NaCl, CaCl2, and MgCl2 systems were examined. Only in the Ca(2+)-containing system did potential responses stay at constant levels against the pH changes, whereas in the other systems, increasing pH caused potential changes, indicating an improvement of cationic permselectivity across the alpha-elastin coacervate membrane. It was suggested that the characteristic Ca2+ transport mechanisms across the alpha elastin coacervate membrane are related in some way to the polypeptide backbone interactions specific and selective to Ca2+ ions. PMID- 1420988 TI - The CD of ligand-DNA systems. 2. Poly(dA-dT) B-DNA. AB - A systematic theoretical study of the CD of [poly(dA-dT)]2 and its complexes with achiral small molecules is presented. The CD spectra of [poly(dA-dT)]2 and of poly(dA):poly(dT) are calculated for various DNA structures using the matrix method. The calculated and experimental spectra agree reasonably well for [poly(dA-dT)]2 but less well for poly(dA):poly(dT). The calculated CD spectrum of [poly(dA-dT)]2 fails to reproduce the wavelength region of 205-245 nm of the experimental spectrum. This discrepancy can be explained by a magnetic dipole allowed transition contributing significantly to the CD spectrum in this region. The induced CD of a transition moment of a molecule bound to [poly(dA-dT)]2 is also calculated. As was the case for [poly(dG-dC)]2, the induced CD of a groove bound molecule is one order of magnitude stronger than that of an intercalated molecule. The calculations also show considerable differences between pyrimidine purine sites and purine-pyrimidine sites. Both signs and magnitudes of the CD induced into ligands bound in the minor groove agree with experimental observations. PMID- 1420987 TI - The contribution of residue ion pairs to the helical stability of a model peptide. AB - Comparative CD measurements were made on the model helical peptides acetylYEAAAKEAXAKEAAAKAamide and acetylYEAAAEKAXAKEAAAKAamide in which X represents a nonaromatic nonionic residue. The former peptide contains three potential i, i + 4 complementary ion pairs at neutral pH, while the latter peptide contains one potential complementary and two potential antagonistic i, i + 4 ion pairs. The effect of pH and ionic strength on the mean residue ellipticity of these peptides was measured at 222 nm and 0 degrees C. These measurements were analyzed assuming a common two-state helix/coil transition and only i, i, + 4 ion-pair interactions. The analyses suggest that the central ion pairs do modulate helical content while the peripheral ion pairs do not, presumably due to the location of the peripheral ion pairs in the frayed ends of the helix. The complementary central ion pair stabilizes the helix by about 0.4 kcal/mole and the antagonistic central ion pair destabilizes the helix by about 0.2 kcal/mole. PMID- 1420989 TI - Shape distributions of protein topography. AB - A method is presented for measuring protein surface shape. It is an improvement of an earlier method that intersects a sphere with the solvent-excluded volume of a protein molecule. The new method, called a shape distribution, produces a more sophisticated description of the region of the sphere inside the protein than is provided by simply measuring the region's area or solid angle. This method is applied to the prediction of molecular complexes in three systems: the hemoglobin nonallosteric interface, trypsin and trypsin inhibitor, and heme and apomyoglobin. It does not uniquely predict the correct structure, even though the individual structures are taken from the experimentally determined complex structure. However, it does provide a list of several hundred predicted complexes, one of which is correct, and from which the correct complex might be extracted by a subsequent chemical filter. PMID- 1420990 TI - IR (vibrational) CD of peptide beta-turns: a theoretical and experimental study of cyclo-(-Gly-Pro-Gly-D-Ala-Pro-). AB - IR vibrational CD (VCD) has been observed for the cyclic pentapeptide cyclo-(-Gly Pro-Gly-D-Ala-Pro-) in solution in CDBr3. The observed VCD spectra do not resemble the VCD features of any of the previously reported peptide secondary structures, such as alpha-helical, "random coil," or sheet structures, and might be due to the beta-turn contained in this molecule. To shed light onto the origin of the observed spectra, VCD intensity calculations, based on the solution and solid-state structures of cyclo-(-Gly-Pro-Gly-D-Ala-Pro-), have been carried out. In addition, calculated VCD data for pure beta-turns are discussed. PMID- 1420991 TI - Hydrophobicity scale for proteins based on inverse temperature transitions. AB - In general, proteins fold with hydrophobic residues buried, away from water. Reversible protein folding due to hydrophobic interactions results from inverse temperature transitions where folding occurs on raising the temperature. Because homoiothermic animals constitute an infinite heat reservoir, it is the transition temperature, Tt, not the endothermic heat of the transition, that determines the hydrophobically folded state of polypeptides at body temperature. Reported here is a new hydrophobicity scale based on the values of Tt for each amino acid residue as a guest in a natural repeating peptide sequence, the high polymers of which exhibit reversible inverse temperature transitions. Significantly, a number of ways have been demonstrated for changing Tt such that reversibly lowering Tt from above to below physiological temperature becomes a means of isothermally and reversibly driving hydrophobic folding. Accordingly, controlling Tt becomes a mechanism whereby proteins can be induced to carry out isothermal free energy transduction. PMID- 1420992 TI - Hydrophobicity of amino acid residues: differential scanning calorimetry and synthesis of the aromatic analogues of the polypentapeptide of elastin. AB - Relative hydrophobicities of aromatic amino acid residues are investigated by using differential scanning calorimetry (DSC) on 10 synthetic copolypentapeptides of poly(VPGVG) of elastin. Utilizing the hydrophobic-driven process of the inverse temperature transition exhibited by these polypentapeptides in aqueous solution, the relative hydrophobicities of Phe, Trp, and Tyr residues are determined by the critical temperature and heat of the transition. The DSC data for the aromatic residue containing copolypentapeptide aqueous solution indicate that tryptophan is the most hydrophobic amino acid residue, phenylalanine the third most hydrophobic on basis of transition temperature and the second on basis of transition heat. For tyrosine, significant differences are observed between the phenolic and the phenoxide anionic states. At pH 7, where tyrosine is protonated, it is found to be the second most hydrophobic amino acid residue on the basis of the transition temperature, whereas on the basis of the heat of transition, it is less hydrophobic than both tryptophan and phenylalanine. Changing the pH from pH 7 to pH 12, for example, for poly[0.8(VPGVG), 0.2(VPGYG)] in aqueous solution shifts the transition temperature from 7 to 49 degrees C with a dramatically reduced heat. On the basis of both the transition temperature scale and the heat of transition, the hydroxylated tyrosine appears less hydrophobic than glycine. PMID- 1420993 TI - Comparative aspects of host-parasite and host-tumor relationships. PMID- 1420994 TI - Tumor necrosis factor-alpha gene expression in the tissues of normal mice. AB - Although TNF-alpha is traditionally associated with macrophage activation during neoplasia and acute inflammation, recent Northern blot hybridization studies indicate that gene expression occurs in the absence of pathology. In order to identify the cellular sources of endogenous message and protein, normal mouse tissues were tested for TNF-alpha mRNA using in situ hybridization and for the corresponding protein by immunocytochemistry. Unexpectedly, specific TNF-alpha message was readily detected in hepatocytes, kidney tubule epithelial cells, various populations of spleen cells and neurons. TNF-alpha protein was present in the same liver and kidney cells as those that contained TNF-alpha mRNA, was low in spleen cells, and was absent in neurons. These results suggest that cells other than macrophages are the major sources of TNF-alpha gene products in normal tissues, indicate that regulation is accomplished by more than one mechanism, and are consistent with the postulate that products of this gene contribute to normal physiological processes. PMID- 1420995 TI - Binding of neutrophil attractant/activation protein-1 (interleukin 8) to resident dermal cells. AB - Putative tissue receptors for leukocyte attractants, including neutrophil attractant/activation protein-1 (interleukin 8, NAP-1/IL-8), have been implicated in the regulation of neutrophil emigration into the tissues. An in-situ binding assay and an ex-vivo autoradiographic approach were used to investigate the binding of radiolabeled NAP-1/IL-8 to human and animal skin. These methods revealed the presence of saturable NAP-1/IL-8-binding sites on the endothelial cells of venules and veins but not arteries or capillaries of the dermis. In addition, the binding of NAP-1/IL-8 to dermal macrophages and perivascular mast cells was observed. We suggest that the NAP-1/IL-8-binding sites described here could be involved in the regulation of NAP-1/IL-8-induced neutrophil emigration. PMID- 1420996 TI - Pharmacokinetics, safety and immunomodulatory effects of human recombinant interleukin-1 receptor antagonist in healthy humans. AB - A phase I study of human recombinant interleukin-1 receptor antagonist (IL-1ra) was conducted in healthy males between the ages of 18 and 30. Twenty-five volunteers received a single, 3 h continuous intravenous infusion of doses ranging between 1 mg/kg and 10 mg/kg IL-1ra. At 3 h into the infusion, plasma IL 1ra levels were 3.1 micrograms/ml and 29 micrograms/ml for the 1 mg/kg and 10 mg/kg doses, respectively. Post-infusion plasma IL-1ra levels declined rapidly, exhibiting an initial half-life of 21 min and a terminal half-life of 108 min. Clinical, hematological, biochemical, endocrinological and immunomodulatory effects were monitored over 72 h and compared to those of four subjects receiving a 3 h infusion of saline. There were no clinically significant differences between the drug and saline groups in symptoms, physical examinations, complete blood counts, mononuclear cell phenotypes, blood chemistry profiles, serum iron and serum cortisol levels. Peripheral blood mononuclear cells (PBMC) obtained after completion of the IL-1ra infusion synthesized significantly less interleukin 6 ex vivo than PBMC from saline-injected controls. These data suggest that transient blockade of interleukin 1 receptors is safe and does not significantly affect homeostasis. PMID- 1420997 TI - Induction of inflammatory cytokine release from cultured human monocytes by C reactive protein. AB - The human acute phase protein, C-reactive protein (CRP), is capable of specifically binding to and modulating the function of mononuclear phagocytes. To investigate whether CRP can also affect the capacity of these cells to produce inflammatory cytokines, enzyme immunoassays and Western blot techniques were used to quantitate interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) produced by freshly-isolated normal human monocytes. CRP induced the rapid release of each cytokine, with significantly elevated levels in culture supernatants at 4 hours and maximal levels of TNF alpha at 8 hours, and of IL-1 beta and IL-6 at 16 hours of culture. The effects of CRP were dose-dependent; greater than 10-fold increases of each cytokine were observed following culture with greater than or equal to 50 micrograms/ml CRP, concentrations which are often found in the presence of moderate to severe inflammation or tissue injury. The induction of cytokine release by CRP was unaffected by inclusion of 25 micrograms/ml polymyxin-B in culture media, but was completely abrogated by prior boiling of the CRP, a procedure which had no effect on induction of monocyte cytokine release by lipopolysaccharide. The dose dependent induction of inflammatory cytokines by CRP provides further support for the hypothesis that interaction with mononuclear phagocytes constitutes an important biological role for this acute phase protein. PMID- 1420998 TI - Interleukin 4 inhibits IL-2-induced proliferation of a human T-leukemia cell line without interfering with p56-LCK kinase activation. AB - Recently we described the establishment in culture and the immunophenotypic and functional characteristics of a human T-leukemia line TALL-103/2 derived from the T-cell receptor (TCR)-gamma/delta subset of T-lymphocytes. TALL-103/2 cells are absolutely dependent on interleukin 2 (IL-2) for their growth and survival in culture and thus provide a model cell line for studies of IL-2 signal transduction in a TCR-gamma/delta T-cell. In this report, we focus on the regulation of SRC-family protein tyrosine kinases (PTKs) by IL-2. TALL-103/2 cells were found to contain p56-LCK, p59-FYN, p62-YES and p53/56-LYN. Stimulation of growth factor-deprived TALL-103/2 cells with IL-2, however, induced increases in the relative activity only of the p56-LCK kinase. This IL-2-mediated increase in LCK kinase activity was manifested both by increased kinase autophosphorylation and by increased phosphorylation of the exogenous substrate enolase during in vitro kinase assays. Furthermore, immunoblot assays determined that the levels of p56-LCK protein were unaltered by IL-2-treatment, indicating that the measured elevations in LCK kinase activity reflected an increase in the specific activity of this PTK. In TALL-103/2 cells, IL-2 stimulated concentration dependent increases in p56-LCK activity that displayed rapid and transient kinetics: detectable increases occurred within 1 minute after IL-2 stimulation, peaked at 10 minutes, and declined to baseline levels by 30 minutes. Treatment of TALL-103/2 cells with IL-4 abrogated IL-2-initiated proliferation, but did not inhibit IL-2-mediated activation of p56-LCK.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1420999 TI - Regulation of synovial cell growth: basic fibroblast growth factor synergizes with interleukin 1 beta stimulating phospholipase A2 enzyme activity, phospholipase A2 activating protein production and release of prostaglandin E2 by rheumatoid arthritis synovial cells in culture. AB - Cytokines have been implicated in the regulation of eicosanoid synthesis and synovial cell proliferation. To further define these mechanisms, we have compared the effects of basic fibroblast growth factor and platelet-derived growth factor on cell growth, prostaglandin E2 (PGE2) production and phospholipase A2 enzyme activity in long-term cultures of synovial cells from rheumatoid arthritis (RA) patients capable of proliferating in serum-free medium. Compared with serum-free medium alone, RA synovial cell growth was significantly enhanced by adding either basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF) to the culture medium. Growing RA synovial cells for 14 days in serum-free medium plus bFGF caused them to spontaneously release significant amounts of PGE2, an effect not seen if cells were grown in serum-free medium alone, or serum-free medium plus PDGF. Enhanced release of PGE2 occurred when arachidonic acid was added to bFGF but not PDGF-treated RA synovial cells, suggesting that bFGF increased cyclooxygenase enzyme activity in these cells. Moreover, phospholipase A2 (PLA2) enzyme activity was found to be significantly greater in RA synovial cells grown for 14 days in serum-free medium containing bFGF alone, or bFGF plus interleukin 1 beta (IL-1 beta) compared with cells grown in either serum-free medium alone, or serum-free medium plus PDGF. Similarly, bFGF plus IL-1 beta stimulated release of PLA2 activating protein, a novel mammalian phospholipase stimulator found in high concentrations in RA synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421000 TI - Presence of interleukin 10 (IL-10) in the ascites of patients with ovarian and other intra-abdominal cancers. AB - Typically, ovarian cancer remains restricted to the peritoneal cavity. Because of this unique localization, the study of ovarian cancer is particularly suitable for immune analysis and for the development of immunotherapy. Here we report that peritoneal fluid from patients with ovarian or other intra-abdominal cancers contained significantly elevated levels of interleukin 10 (IL-10) (542 +/- 77 pg/ml, N = 35), compared with peritoneal fluid from patients with benign gynecological conditions (34.2 +/- 7.5 pg/ml, N = 63) (P < 0.001). Peritoneal fluid IL-10 levels did not correlate with histology, tumor stage, grade, or prognosis. IL-10 levels were also elevated in the serum of patients with intra abdominal cancer (1353 +/- 906, N = 8). Established ovarian cancer cell lines (N = 5) did not produce any detectable IL-10. Investigation of the cell surface phenotype of the cells in the peritoneal cavity indicated the presence of significant amounts of activated immune cells. The presence of cytokines such as IL-10 in the peritoneal cavity of ovarian cancer bearing patients could be important in the growth and development of cancer, more specifically, in relation to host immune responsiveness. PMID- 1421001 TI - The autocrine role of tumor necrosis factor in the proliferation and functional differentiation of human lymphokine-activated T killer cells (T-LAK) in vitro. AB - The autocrine role of tumor necrosis factor alpha (TNF) in the proliferation and functional differentiation of human lymphokine-activated T-killer cells (T-LAK) in vitro was investigated. Human peripheral blood lymphocytes initially stimulated with IL-2 and phytohemagglutinin-P (PHA) for 48 h will proliferate for long periods in vitro in the presence of IL-2. These T-LAK cells have been shown to be 95% CD3 positive. Employing ELISA techniques, greater than 500 pg/ml of TNF was found to be released in the supernatants of these cells during the first 5 days of culture. However, the levels dropped to 100-200 pg/ml by days 7-10. T-LAK cells grown from days 7 to 10 in the presence of IL-2 and rabbit anti-TNF were significantly growth inhibited (up to 23%). The cytolytic activity of T-LAK cells grown from days 0 to 7 in the presence of anti-TNF was also decreased (up to 75%). Phenotypic analysis of these anti-TNF treated T-LAK cells revealed a decrease in CD8 expression (up to 12%) and increase in CD4 expression (up to 27%) when compared with control cells. The data suggest that TNF has a regulatory role in the growth and functional differentiation of these human T-LAK cells. PMID- 1421002 TI - In-vitro stimulation of TNF-alpha from human whole blood by cell-free supernatants of gram-positive bacteria. AB - Gram-positive bacteria are being recognized increasingly as the cause of shock like syndromes, clinically indistinguishable from those seen in association with Gram-negative endotoxic shock. Much clinical and experimental data link tumour necrosis factor-alpha (TNF-alpha) with the pathogenesis of endotoxic shock, and a number of studies of individual Gram-positive species have also implicated TNF alpha. We report here the first systematic study of the ability of cell-free supernatants of common Gram-positive bacteria to induce TNF-alpha from human peripheral blood monocytes in vitro. Almost all the 63 strains were able to induce TNF-alpha, although the levels were substantially lower than those obtained from supernatants of Gram-negative bacteria, used as controls. Streptococcus pneumoniae, S. pyogenes, viridans streptococci and coagulase negative staphylococci were consistently more active than group B and D streptococci. TNF-alpha induction did not correlate with conventional markers of pathogenicity; amongst strains of Staphylococcus aureus, commensal and blood culture isolates did not induce significantly different amounts of TNF. We conclude that cell-free supernatants of most Gram-positive bacteria are capable of inducing TNF-alpha from human peripheral blood monocytes in vitro, but the significance of this finding remains to be determined. PMID- 1421003 TI - Welcan units. PMID- 1421004 TI - Cytological evaluation of the effect of Tamoxifen in premenopausal and post menopausal women with primary breast cancer by analysis of the karyopyknotic indices of vaginal smears. AB - The influence of Tamoxifen on the vaginal epithelium of 33 premenopausal and 99 post-menopausal women with primary advanced breast cancer was investigated. The karyopyknotic index (KPI) values were assessed before starting therapy and at monthly intervals during therapy with Tamoxifen. A decrease in the KPI in menstruating women and a slight but definite increase in KPI values in post menopausal women were observed. PMID- 1421005 TI - Well differentiated follicular neoplasms of the thyroid: reproducibility and validity of a 'decision tree' classification based on nucleolar and karyometric features. AB - This study was conducted on fine-needle aspirates of well differentiated follicular neoplasms of the thyroid. A 'decision tree' classification based on the percentage of nucleolated nuclei, percentage of nuclei with two or more nucleoli and mean major nuclear diameter was adopted. We observed that the reproducibility and the validity of the follicular adenoma vs follicular carcinoma discrimination are greater than in the subjective evaluation. Moreover, similar classification results were obtained when measurements were performed either with a fully automated image analysis system or with semiautomatic or manual instrumentation. As for reproducibility of the inter-instrument comparisons, the k statistic values ranged from 0.85 to 1.00 (mean value 0.90, that is, an 'almost perfect' degree of agreement); in the subjective evaluations, the inter-observer comparisons showed values ranging from 0.20 to 0.56 (mean value 0.37, that is, 'fair'). In the decision tree classification, feature value thresholds were selected in order to have specificity of 100% and the predictive value of a positive result (carcinoma) of 100%; accuracy was 87% (range 86-89%), sensitivity 74% (71-79%), the predictive value of a negative result (adenoma) 79% (78-82%). In the subjective evaluation the values were as follows: accuracy 67% (64-71%), sensitivity 57% (50-64%), specificity 77% (71-79%), predictive value of a negative result (adenoma) 64% (61-69%), predictive value of a positive result (carcinoma) 71% (67-75%). The conclusion is that, by using a routine microscope equipped with a micrometer, the preoperative diagnosis of follicular carcinoma from smears can be formulated with a high degree of certainty. PMID- 1421006 TI - Nucleolar organizer regions in pituitary gland adenomas. AB - Nucleolar organizer regions are DNA segments concerned with the synthesis of ribosomal RNA (rRNA). Some specific proteins related to NORs can be demonstrated by a silver technique and are then referred to as Ag-NORs. The mean number of Ag NORs per cell has been used as a marker of cell proliferation in recent years and there is some evidence to suggest that Ag-NOR counts can be used to differentiate between normal and neoplastic cells. Paraffin block sections of 42 pituitary gland adenomas and 24 normal adult pituitary glands have been examined using the Ag-NOR staining technique. Touch imprints of nine adenomas and 12 normal adult pituitary glands were also examined using the same Ag-NOR staining technique. Using light microscopy at x2000 magnification, the Ag-NORs were located as black dots in the cell nuclei and the mean number of Ag-NORs per cell was determined. No significant difference was observed between blocked sections and imprints of adenomas or between imprints and paraffin sections of normal glands. However, a significant difference was observed between the mean number of Ag-NORs in pituitary gland adenomas and normal glands in paraffin block sections and touch preparations (P less than 0.001). The modified Ag-NOR technique can be a useful aid in the differential diagnosis between normal pituitary gland tissue and pituitary adenomas, especially during surgical operations. PMID- 1421007 TI - Leiomyosarcoma of the breast; cytological and histological features, with a review of the literature. AB - This report describes the cytological and histological features of a leiomyosarcoma of the breast. The differential diagnosis of this rare tumour is discussed. Eleven well documented cases of leiomyosarcoma of the breast have been reported previously and details of these are included in this review. PMID- 1421008 TI - Cytological appearances of a solitary squamous cell papilloma with associated mucous gland adenoma in the lung. AB - Solitary papillomas of the lung are rare. They are usually squamous but mixed squamous cell papilloma and mucous gland adenoma can occur. We report for the first time the cytological findings of a fine needle aspirate from a mixed squamous cell papilloma and mucous gland adenoma from the lung periphery. PMID- 1421009 TI - Peripheral low-grade mucoepidermoid carcinoma of the lung--needle aspiration cytodiagnosis and histology. AB - Mucoepidermoid carcinoma of the lung is a rare tumour, and is not usually considered in the differential diagnosis of a peripheral lung mass. The cytological and histological features of an intimate admixture of polygonal intermediate cells, well differentiated mucinous and squamous cells, as illustrated in this case report, serve to differentiate a well differentiated mucoepidermoid carcinoma from adenosquamous carcinoma, low grade adenocarcinoma, bronchioloalveolar carcinoma, and benign reactive changes. PMID- 1421010 TI - Comparison of granulocyte-macrophage colony stimulating factor and interleukin-1 production from human peripheral blood mononuclear cells as measured by specific radioimmunoassays. AB - Attention has focused on cytokine networks in which gene and protein expression of some cytokines is under the influence of other cytokines. In the present studies, we addressed the relationship between the synthesis of granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-1 (IL-1) in human peripheral blood mononuclear cells (PBMC) stimulated with mitogens. Since bioassays for cytokines are sensitive to more than one of these factors, it was necessary to measure the amounts of IL-1 and GM-CSF independent of bioassays. A specific and sensitive (40 pg/ml) radioimmunoassay (RIA) was developed for human GM-CSF. The sensitivity of the RIA was greater when lysine residues were iodinated with Bolton-Hunter reagent than tyrosine residues using chloramine T. After stimulating PBMC with concanavalin A (Con A), the biological activity of GM CSF was determined in bone marrow cultures and compared to immunoreactive GM-CSF; GM-CSF levels detected by bioassays and RIAs were highly correlated in two separate sets of experiments (r2 = 0.95 and 0.43). Incubation with Con A for 48 h induced more GM-CSF than stimulation by phytohemagglutinin (PHA) despite the fact that PHA stimulates large amounts of IL-1 alpha; indomethacin had no effect on Con A stimulated synthesis of GM-CSF or IL-1 alpha. In two separate studies, PBMC from 14 donors and a second group of 12 donors were incubated with Con A for 48 h and the total amount of immunoreactive IL-1 alpha and GM-CSF was determined in the same cell cultures. There was no correlation of the amount of either cytokines in these cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421011 TI - Activation of the systemic production of tumor necrosis factor after exposure to acute stress. AB - Tumor necrosis factor (TNF), which was originally identified as a tumoricidal factor, is now regarded as one of the main regulators of inflammation and various immune systems. Thus it has been considered to be mobilized in case of emergency. However, we assume that TNF and the cytokine network driven by the monokine also function under normal condition for homeostasis of the animal body which is exposed to various kinds of physiological stress. To test this possibility, we exposed C3H/He mice for up to 3 days to five types of acute stress: food deprivation, drinking water deprivation, sleep deprivation, swimming, and physical restraint. After release from the stress, the level of priming for systemic production of TNF was examined using OK-432 (a streptococcal preparation) as a trigger. Priming of TNF production was not observed immediately after 2-day exposure to most of the stressors. Sleep deprivation alone tended to induce a primed state especially when the stress period was lengthened to 3 days. On the other hand, by keeping mice in a normal condition for a 2-day restorative interval after 2-day exposure to the stressors, systemic production of TNF was consistently primed for all the stress examined. The time course of the priming effect was examined in detail for water-deprivation stress. The effect was detected as early as 3 hours after release from stress, was sustained for 2 days, and returned to the basal level by 4 days after the release. Based on these results, we discussed the role of the TNF-driven cytokine circuit in adaptation to stress. PMID- 1421012 TI - Interleukin-2 and blood brain barrier in cats: pharmacokinetics and tolerance following intrathecal and intravenous administration. AB - Single bolus doses of glycosylated human interleukin-2 (n IL-2) in the range of 2.8 x 10(3) to 2.0 x 10(6) IU/kg were administered to anesthesized cats via the cephalic vein (n = 10) or using suboccipital puncture (n = 8). CSF (cerebrospinal fluid) and blood samples were collected by repeated puncture. The n IL-2 concentration in four cats was determined on the basis of its biologic activity using 3H-thymidine incorporation into human ConA-blasts and by radioimmunoassay. In additional experiments radioactivity was determined in cerebrospinal fluid and serum after intravenous and intrathecal (i.th.) application of 5.8 x 10(3) - 3.2 x 10(3) IU/kg of 14C-acetyl-n IL-2 in regular time intervals. CSF and serum concentration time-profiles show a biexponential decline in the plasma elimination phase with half-lives of 4 min (alpha-phase) and 90 min (beta-phase) after intravenous and 20-120 min (alpha-phase) and 2-16 hours (beta-phase) after intrathecal application. There is a trend towards longer terminal elimination half-lives with increasing doses. Interleukin-2 is able to penetrate the blood brain barrier from the circulation into the cerebrospinal fluid and vice versa. Due to a slow rate of penetration and rapid elimination from blood only traces of n IL-2 (2-8 IU/ml) are detected in CSF after i.v. injection of 2 x 10(6) IU/kg, whereas concentrations between 400 and 1600 IU/ml are maintained in CSF for several hours following i.th. administration of 2-10 x 10(5) IU/kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421013 TI - The roles of IL-4, TGF-beta and LPS in IgA switching. AB - CH12.LX B cells have been used as a lymphoma model of MHC restricted, antigen dependent B cell differentiation. These B cells express surface IgM and secrete IgM. Most recently we have demonstrated that CH12.LX is a model of cytokine driven IgA differentiation. Recently, transforming growth factor beta (TGF-beta) has been shown to be a probable switch factor for IgA in LPS-stimulated mouse lymphocytes, therefore we chose CH12.LX B cells to study the effect of IL-4, TGF beta and LPS in IgA isotype switching. Adding TGF-beta to the monoclonal cell line CH12.LX results in induction of mIgA expression but no enhancement of IgA secretion similar to the effect of IL-4. The addition of LPS serves as a non specific stimulus to enhance the secretion of the expressed immunoglobulin, but has no IgA specific activity of its own. IL-4 and TGF-beta together are synergistic for mIgA expression. Pretreatment studies show that TGF-beta added after IL-4 is the same as TGF-beta alone whereas the converse is the same as adding both cytokines together. TGF-beta acts by increasing the steady state levels of alpha message, whereas northern analysis indicates that IL-4 does not induce alpha message the way TGF-beta does. These data confirm that TGF-beta by itself is an isotype switch factor for IgA. In addition, IL-4 and TGF-beta cause mIgA expression through different mechanisms. CH12.LX B cells serve as a valuable model to study the role of multiple signals required for mIgA expression and IgA secretion. PMID- 1421014 TI - Inhibition of morphine dependence by a lipopolysaccharide from Pantoea agglomerans. AB - A lipopolysaccharide from Pantoea agglomerans (LPSp) was purified and examined for relief of morphine dependence by observing its inhibition of the jumping of mice on naloxone-precipitate withdrawal. Administration of LPSp either intravenously or intradermally showed marked inhibition of the jumping. Beta endorphin in mouse serum and brain tissue were recognized to be in synchrony with the time course of the relief. Administration of TNF-alpha gave similar effect, suggesting that LPSp induces a cytokine cascade to produce endogenous TNF followed by ACTH/beta-LPH gene products and beta-endorphin. The effect of LPSp was better than that of LPS from E. coli or Bordetella pertussis, and thus is considered to be applicable for clinical use. PMID- 1421015 TI - Interleukin-1 and tumour necrosis factor production by human monocytoid cells: study on a single cell level. AB - Human IL-1 beta and TNF alpha production by normal and transformed monocytoid cells was studied using biological assays, cytokine specific ELISA and by immunocytochemical methods on a single cell level. Quiescent human blood monocytes and cultured in vitro transformed human monocytoid cell lines U-937, THP-1 and HL-60 did not contain IL-1 beta and TNF alpha in their cytoplasm. IL-1 beta synthesis and secretion was induced by LPS stimulation in nearly 90% monocytes, 15-20% U-937, 3-5% THP-1 and in no HL-60 cells. Normal human blood monocytes had a more rapid kinetics of IL-1 beta synthesis. IL-1 beta positive cells stained with antibodies to human IL-1 beta appeared at 1-2 hours after LPS application, while in monocytic cell lines only after 4-6 hours. Using immunoperoxidase staining of U-937 cells pulse labelled with 3H-thymidine, it was shown that proliferating cells did not synthetize IL-1 beta. Instead of IL-1 beta, TNF alpha could be induced by LPS in U-937 cells only after preliminary differentiation with PMA. Recombinant IL-1 beta induced a very low level of TNF alpha production in PMA-treated cells. Similarly recombinant TNF alpha alone induced IL-1 beta synthesis only in a few U-937 cells. PMID- 1421017 TI - Gender inequalities in care-giving in Canada. AB - In Canada today, as in the past, men and women devote different amounts of time and effort to providing health care to their family and in the broader community. This paper examines "the social distinction between masculinity and femininity" in care-giving. Issues of gender inequality in care-giving have the potential to affect the formal health care system as the burden of caring will increase over the next few decades with the aging of society. This increase in need for care is occurring at a time when primary care providers--women--have additional demand on their time. Canadian society has been facing a series of social, demographic and economic shifts such as a higher divorce rate, two-income families, women's increasing professional commitments and first pregnancies at later ages, these factors may not affect women's willingness to care for others. However women may need support to provide the care. Assuming present trends, increasing need for families to care for elderly relatives may be inevitable. Perhaps society will recognize this need and provide support to those providing informal care. This could take the form of allowing individuals more time to provide care through child care leave, leave to care for parents and job-sharing. Support to those providing informal care might also be facilitated through community support services such as respite care, household maintenance, psychological support to care-givers, support groups, informal networks within a community and consideration of unconventional support methods. PMID- 1421016 TI - A statistical chronicle of tuberculosis in Canada: Part I. From the era of sanatorium treatment to the present. AB - This report marks over 50 years of publication by Statistics Canada of annual reports on tuberculosis statistics. These years have witnessed what has been described as a conquest of tuberculosis in Canada. To quote George Jasper Wherrett in The Miracle of the Empty Beds: One hundred years ago the word consumption (as tuberculosis was then called) struck horror in human hearts. Today, in the western world, it barely evokes any emotion save a too easy surprise that it still exists. This statistical chronicle of tuberculosis in Canada is divided into two parts. Part I: From the Era of Sanatorium Treatment to the Present pulls together data from yellowed-with-age reports on tuberculosis and vital statistics, historical accounts and modern computer files, to document the changes in tuberculosis incidence and mortality over past decades to the present. Part II: Risk Today and Control takes a closer look at those most vulnerable to contracting tuberculosis. It also looks at the future, the need for maintaining and, indeed, strengthening vigilance, and the work yet to be done to eradicate tuberculosis in Canada. The fight against tuberculosis is far from over. PMID- 1421018 TI - Mortality differentials between three populations--residents of Scandinavia, Scandinavian immigrants to Canada and Canadian-born residents of Canada, 1979 1985. AB - The study compares the mortality of Canadian residents born in Canada and Scandinavia (Finland, Sweden, Norway, Denmark) to the mortality of the four Scandinavian countries. The study focuses on the mortality experience of anyone who was 35-74 years old during the period 1979-85. Swedish and Norwegian populations both in Scandinavia as well as immigrants to Canada had relatively low mortality from all causes of death. On the other hand, populations in Finland and Denmark had comparatively higher mortality from certain causes of death. Finnish excess mortality from cardiovascular diseases and from external causes of death was present in Finnish living in Scandinavia as well as in Finnish immigrants to Canada. This contrasted with the excess mortality from non cardiovascular disease in the population of Denmark which was not reflected in the mortality of Danish immigrants to Canada. Finally, the cardiovascular mortality of all Scandinavian-born immigrants to Canada was found to be lower than in their respective countries of origin. The article includes a discussion of possible explanations for these results. PMID- 1421019 TI - 1992 Canadian Cancer Statistics. AB - In Canada, it is estimated that in 1992 115,000 new cases of cancer will be diagnosed. This total excludes 47,200 estimated new cases of non-melanoma skin cancer. The number of new cases is increasing by about 3,000 per year due partly to the aging population, improved registration, earlier detection of cancer and real increases in the incidence of some types of cancer. It is estimated that there will be 58,300 cancer deaths in 1992. By 1992, prostate cancer will have overtaken lung cancer as the leading cancer among men in the four western provinces while lung cancer is expected to exceed breast cancer as the leading cause of cancer deaths among women in some provinces, notably British Columbia. In British Columbia, the relative survival rates for most cancers improved between the periods 1970 to 1974 and 1980 to 1984. However, stomach, lung and pancreatic cancers, which have low survival rates, showed little improvement. This article is based on 1992 estimates of cancer incidence and mortality, cancer trends in Canada and relative cancer survival rates in British Columbia, found in Canadian Cancer Statistics 1992. This publication was prepared at Statistics Canada through a collaborative effort involving the Canadian Cancer Society, Health and Welfare Canada and the provincial/territorial cancer registries. PMID- 1421020 TI - Health care and health status. A Canada--United States statistical comparison. PMID- 1421021 TI - Highlights. Causes of death 1990. PMID- 1421022 TI - Historical publication highlights: selected birth and fertility statistics, Canada, 1921-1990. PMID- 1421023 TI - Hospital morbidity, 1989-90. PMID- 1421024 TI - List of residential care facilities, 1991. PMID- 1421025 TI - Mental disorders, 1989-90. PMID- 1421026 TI - Nursing in Canada. PMID- 1421027 TI - Surgical procedures, 1989-90. PMID- 1421028 TI - Therapeutic abortions, Canada and the provinces, 1990. PMID- 1421029 TI - Is the AIDS virus responsible for the disease? PMID- 1421030 TI - Retrospective study correlating clinical infectious history and peripheral blood T-cell subpopulations in cancer, GvH and HIV+ patients. AB - The CD4+ CD8- inducer helper cell and the CD4- CD8+ cytotoxic/suppressor cell absolute numbers were measured in the peripheral blood of patients with various pathological conditions: with leukemia-lymphomas or solid tumors, patients with bone marrow grafts suffering from GvH, HIV-1 asymptomatic carriers, ARC and AIDS patients. The study was carried out during observation periods when they were not suffering from opportunistic infections and were untreated. In all the groups a decrease of the CD4+ CD8- cell absolute number was observed. In the leukemia lymphoma and solid tumor bearing patients the CD4- CD8+ absolute value was lower than normal, while in the GvH- and HIV-infected patients, it was significantly higher. The clinical follow-up of each group indicates that GvH, ARC and AIDS patients developed infection in 40-68% of the cases, ie the only groups at risk of infection are those in which the CD4- CD8+ absolute values are high: we suggest that the balance CD4+ versus CD8+ should be considered rather the absolute CD4+ when discussing appropriate use of immuno-regulators. PMID- 1421031 TI - Analysis of purine nucleotides in lymphocytes from healthy subjects and AIDS patients. AB - The most important purine nucleotides (NAD, AMP, IMP, GMP, XMP, ADP, ATP, GDP, GTP) were analyzed by HPLC in the lymphocytes of healthy subjects and HIV-1 seropositive patients at different stages of the disease (ARC-AIDS). Several differences, which focus attention on the behaviour of purine nucleotide metabolism in the lymphocytes of these patients, were observed. PMID- 1421032 TI - The role of drugs in the origin of AIDS. AB - It is proposed that the new American and European AIDS epidemics are caused by recreational and anti-HIV drugs rather than by human immunodeficiency virus (HIV). Chronologically, the AIDS epidemic in the 1980s followed a massive escalation in the consumption of recreational drugs that started in the 1960s and 70s. Epidemiologically, both epidemics derive about 80% of their victims from the same groups of 20-44 year-olds, of which 90% are males. In America 32% of these are intravenous drug users and their children, about 60% are male homosexuals who are long-term users of oral aphrodisiac drugs and an unknown percentage are prescribed the cytotoxic DNA chain terminator AZT, as inhibitor of HIV. Direct evidence indicates that these drugs are necessary for HIV-positives and sufficient for HIV-negatives to develop AIDS diseases. The drug-AIDS hypothesis predicts correctly that: (i) AIDS is new in the US, because the drug epidemic is new, while the HIV epidemic is old--fixed at a constant 1 million Americans since 1985; (ii) despite an increase in venereal diseases, AIDS remains restricted to long-term drug users and small groups with clinical deficiencies; (iii) over 72% of AIDS occurs in 20-44 year-old males, because they make up over 80% of hard psychoactive drug use; (iv) distinct AIDS diseases correlate with the use of distinct drugs, eg Kaposi's sarcoma with nitrite inhalants, tuberculosis with intravenous drugs, and leukopenia, anemia, and nausea with AZT; (v) AIDS diseases are only acquired after long-term drug consumption, rather than after single contacts as the virus-hypothesis predicts. The drug hypothesis can be tested epidemiologically and experimentally in animals. It predicts that most AIDS can be prevented by stopping the consumption of drugs, and provides a rational basis for therapy. PMID- 1421033 TI - Serum bone alkaline phosphatase and CA 549 in breast cancer with bone metastases. AB - A monoclonal radioimmunometric assay for bone alkaline phosphatase (BAP) developed by Hybritech, USA, with an upper limit of normal of 40 U/l, was examined in 125 patients with breast cancer. Eleven patients who remained tumour free for 5-6 years had small intra-individual variations of BAP. The median value in 33 patients with multiple bone metastases of 60 U/l was elevated when compared with that in 40 patients with no evidence of metastases (22 U/l) and 34 U/l in 16 with limited bone disease (1-2 hot spots). By contrast, only 2 out of 25 patients with extensive local recurrence, lung, or hepatic metastases, without bone involvement showed an increase of BAP (< 200 U/l). The BAP levels were compared to total alkaline phosphatase (TAP), the breast cancer marker CA 549 (HybriBREScan). Longitudinal studies of 15 patients with bony metastases showed that TAP and BAP were well correlated only when the TAP was elevated; CA 549 and BAP could vary independently. The main use of BAP in patients with bone metastases appears to be an aid to the monitoring of treatment; however, it is not significantly raised in limited bone metastases. PMID- 1421034 TI - Serum erythropoietin levels in hemodialysed patients after administration of recombinant human erythropoietin. AB - In anemic patients on regular hemodialysis (HD), correction of anemia with recombinant human erythropoietin (rHuEpo) administered intravenously (iv) or subcutaneously (sc) was followed over a 2-month period. Monitoring serum Epo post dose concentrations after the first iv rHuEpo injection and following another regular injection after 2 months of therapy with rHuEpo iv in 9 patients showed that the Epo elimination half-life was reduced from 7.48 h to 4.68 h. In the same patients the initially low percentage of erythroblasts and mature erythroid progenitors increased during 2 months of rHuEpo therapy. Because Epo molecules bound to Epo receptors are internalized in target cells we suggest that the expansion of the Epo responsive cell pool could explain the shorted Epo elimination time after 2 months of rHuEpo treatment. By monitoring serum Epo concentration following sc rHuEpo injection in 7 HD patients it was found that the modest increase in serum Epo levels (30-60 mU/ml) was sufficient to correct anemia. PMID- 1421035 TI - Levels and variability of purine nucleotides in normal human lymphocytes. AB - Anion-exchange, high performance liquid chromatography was used to determine purine nucleotides in lymphocytes of healthy males and females of various ages. We observed a considerable dispersion of values which were unrelated to age or sex, possibly linked to various states of activation of circulating lymphocytes and to other unknown factors. PMID- 1421036 TI - TSH binding site structures in human eye muscle fractions identified by using covalent-crosslinking. AB - 125I-labelled human TSH was crosslinked to the human thyroid and extraocular eye muscle membrane and cytosol fractions (which were obtained by centrifugation). Studying crosslinking of 125I-labelled TSH to the thyroid fractions, TSH binding sites' structures were demonstrated on the eye muscle membranes and in the cytosol fractions. The binding of 125I-labelled TSH was inhibited by the addition of 120 mIU/mL of unlabelled TSH (and not with 12 mIU/mL) which confirmed the presence of TSH binding sites structures (MW about 66,000 Da) on the eye muscle membrane and in its cytosol. Adding purified IgG fractions from the sera from controls and Graves' disease (with high titer of antibodies against TSH receptor) to the thyroid and eye muscle membranes and cytosol fractions, the binding of 125I-labelled human TSH was inhibited by molecular weight of about 66,000 Da in the cytosol fractions. The affinity constant of the binding sites in the human eye muscle cytosol and the number of TSH receptors were found to be 146 x 10(9) M 1 and 9.8 x 10(10) molecules/mg/mL by Scatchard analysis, respectively. PMID- 1421037 TI - Transplantation, immunity, tolerance and grafts. Dempster, Hasek "et les autres". PMID- 1421038 TI - Current problems in organ transplantation. AB - Organ transplantation has evolved over the past 30 years, although 'new' and 'old' problems remain unsolved, which from a personal point of view, might be summarized as: i) the transfusion effect; ii) HLA matching and pre-graft sensitization of the potential recipient; iii) immunosuppressive drugs; iv) the pathogenesis of chronic rejection; v) infections; vi) de novo cancers. The aim is to attain a state of specific immunological tolerance without the use of immunosuppressive drugs. PMID- 1421039 TI - Current status of allogeneic bone marrow transplantation. AB - Use of allogeneic bone marrow transplants continues to increase. During the 36 year period between 1955 and 1990, more than 33,000 patients received allogeneic bone marrow transplants; more than 45% of these were performed during the 3 years 1988-1990. Transplants are effective therapy for leukemia and other hematologic diseases. It is widely considered that transplants are the treatment of choice for aplastic anemia and chronic myelogenous leukemia, those who fail conventional therapy for acute leukemia and a variety of genetic, metabolic and immune deficiency disorders. Successful application of bone marrow transplantation is limited by complications such as graft failure, graft versus host disease GVHD and interstitial pneumonia and, until recently, the requirement for an HLA identical sibling donor. In the past few years, an increasing number of transplants were performed using unrelated or HLA-partially matched related donors with some success. Development of post-transplant complications can often be predicted by risk factor assessment. In this report, current data from the IBMTR are summarized and several risk factors affecting outcome identified. PMID- 1421040 TI - Pancreas and islet transplantation in man. AB - The results of pancreas transplantation have greatly improved, the overall patient and graft 1-year survival rates now being 89 and 62%, respectively. A technically successful graft ensures a near-normal glucose metabolism in most cases, and improves the patient's quality of life. However, pancreas transplantation is not a life-saving procedure and because of the necessary permanent immunosuppression it is usually performed in patients in whom a kidney transplant is needed or has been previously established. In such patients the other diabetic chronic complications are often advanced and limit the potential benefit of pancreas transplantation, but it seems premature to extend the indications to early stage diabetes. Islet transplantation has many potential advantages, mainly the possibilities of immune alteration and immune protection of the transplant that could allow transplantation to be performed without immunosuppression and the use of xenogenic tissue. Major limiting factors are the high numbers of islets necessary to ensure insulin independence and the low yield of islet isolation from adult pancreas. Encouraging, albeit preliminary results have been recently reported in man. PMID- 1421041 TI - Liver transplantation: the challenges of the 1990s. AB - An enormous increase in liver transplantation has been observed over the last decade since it now represents a suitable therapeutic option for patients with end-stage liver disease. The overall one-year survival rate is about 75% for adults and 85% for children, when fulminant hepatic failure and malignancies are excluded. Such improvements in both survival and quality of life are due to many concurrent factors: better timing and selection; development of the UW solution for liver preservation; improvement in operative management including surgical technique, veno-venous bypass and cell-saver; progress in intensive care management of immunosuppressed patients. Nevertheless, the increasing demand for livers is now confronting the transplant teams with organ shortage, for which the introduction of graft reduction, hepatic biparition and living-related donation will contribute to alleviate the scarcity of donors. As a consequence of the increasing number of long-term survivors, greater efforts are now being directed towards the long-term outcome after liver transplantation: disease recurrence, the need for permanent immunosuppression and the quality of rehabilitation will become the challenges of the 1990s before reaching the next step towards multiple organ transplantation. PMID- 1421042 TI - Allogenic recognition in 1992. AB - Many new data have been obtained in the last 4 years concerning the structure and functions of major histocompatibility complex (MHC) molecules. Structural data are summarized and the functions of MHC molecules in the presentation of peptides to T cells are described. The high selectivity of peptides binding to MHC molecules is discussed. The negative and positive selection of T cells in the thymus is described and the notion of repertoire introduced. The consequences of these new data on the understanding of H2 restriction and alloreactivity are described. The four potential types of alloreactivity are defined: i) house keeping gene (HKG) peptides bound to allogenic MHC molecules; ii) allogenic peptides (derived from allogenic MHC molecules) bound to allogenic MHC molecules; iii) empty allogenic MHC molecules; iv) allogenic peptides bound to autologous MHC molecules. In fact, the allogenic response is mostly directed toward HKG peptides bound to the allogenic MHC molecules of the graft cells (type 1). The potential role of type four alloreactivity in rejection is discussed. PMID- 1421043 TI - Endoscopic ultrasonography in colorectal diseases. AB - Since new flexible high-frequency ultrasound endoscopes are now available, the use of this technique in colorectal disease has been determined. Its role in the preoperative staging of rectal cancer, and in follow-up after surgery has been established, but its use in cases of anal cancer and in non-neoplastic rectal diseases still has to be demonstrated more precisely. PMID- 1421044 TI - Surgical endoscopy in thoracic surgery. AB - From November 1990 to April 1992, 32 patients were operated on by video thoracoscopic surgery (VTS). Included were 22 males and 10 females, mean age 47.6 years. VTS has been used therapeutically on 25 occasions: 20 spontaneous pneumothoraxes; two recurrent pleuritis; two cysts; one mediastinal; one pulmonary; and one thoracic sympathectomy. VTS was also used diagnostically seven times: five lung biopsies and two mediastinal lymph node biopsies. It was necessary to perform a mini-thoracotomy in one patient and proceed to immediate thoracotomy in three patients. There were no deaths in this series, the morbidity was two patients with collapsed lungs, one of which required drainage. VTS must be performed under standard thoracic surgical conditions: selective intubation, and fully equipped to make an immediate thoracotomy. The advantages of VTS are aesthetic and functional, the post-operative pain is reduced in intensity and duration. At present, VTS is indicated for the treatment of spontaneous pneumothorax, the assessment and biopsy of mediastinal lymph node and the excision of some lung lesions. Improvements in the apparatus should lead to a broadening of these indications in the future. PMID- 1421045 TI - Non-surgical management of bile duct stones. AB - Endoscopic sphincterotomy with stone extraction is the non-surgical method of choice for treatment of choledocholithiasis in patients unfit for surgery or with previous cholecystectomy. Its success rate is 85-90%. Many adjunctive methods have been developed to increase the clearance rate after initial failure and are reviewed in this paper. Collaboration among the surgeon, endoscopist and radiologist offers the patient a high opportunity for successful clearance of common bile duct (CBD) stones with the least morbidity and mortality. The application of endoscopic sphincterotomy combined with laparoscopic cholecystectomy to younger patients is now debated. PMID- 1421046 TI - Immunogenicity of combined anti-HIV and anti-suppressive vaccine preparations. AB - HIV-1 antigens generate in man both a humoral and cellular immune reaction. However, in ARC/AIDS patients, the cellular response is inhibited by HIV-1 which induces an antiproliferative (suppressive) effect on activated T cells. To overcome this inhibition and up-regulate the cellular response, we designed a new vaccine strategy directed both against HIV-1 and immunosuppression and we used an immunizing preparation composed of HIV-1 antigens combined with immunoregulatory peptides prepared in a biologically inactivated but immunogenic form. In mice, this preparation induced anti-HIV-1 antibodies and a cell-mediated cytotoxicity directed against H2 restricted cells carrying HIV-1 antigens. PMID- 1421047 TI - Effect of pinaverium bromide on jejunal motility and colonic transit time in healthy humans. AB - Pinaverium bromide is a specific calcium channel blocker used in the treatment of irritable bowel syndrome (IBS) for its spasmolytic activity. The aim of the present study was to evaluate the effect of orally administered pinaverium bromide on jejunal motility and total and segmental colonic transit time in control subjects. Gastrointestinal studies were performed in 10 healthy volunteers (30 +/- 3 years), before and after a treatment phase of 14 days (150 mg/d). Jejunal motility was measured by prolonged manometry (14 h) and colonic transit time by a multiple ingestion, single marker technique. No significant modification of phase III of the migrating motor complexes was demonstrated. On the contrary, a significant (p < 0.01) but weak decrease of the frequency of contraction was found. Unlike previous studies, no decrease of total or segmental colonic transit time was demonstrated. PMID- 1421048 TI - Minocycline and benign intracranial hypertension. AB - A case is reported of a 16-year-old girl who developed benign intracranial hypertension, with severe bilateral papilledema after minocycline therapy. A lumboperitoneal bypass was carried out in view of the ophthalmologic signs and the pressure of cerebrospinal fluid. PMID- 1421049 TI - Displacement of rifampicin bound to serum proteins by addition of levamisole. AB - We have studied, by ultrafiltration, the interactions between rifampicin (15 and 30 microM) and levamisole (7 microM) since both drugs may be associated for the treatment of brucellosis. We can observe a statistically significant increase in the free plasmatic fraction of rifampicin at the studied concentration of levamisole, which indicated that levamisole reduced rifampicin bound to proteins (290 and 250%, respectively). PMID- 1421050 TI - Comparative bioavailability and steady state fluctuations of Tegretol commercial and carbamazepine OROS tablets in adult and pediatric epileptic patients. AB - The comparative bioavailability and steady state fluctuations resulting from the administration of Tegretol 200 mg commercial tablets and carbamazepine OROS controlled delivery tablets were investigated in 22 adult and 12 pediatric epileptic patients. Tegretol commercial tablets were dosed according to previously established clinical regimens of 400 to 2000 mg daily doses divided into four equal or unequal intervals. Carbamazepine OROS was dosed every 12 h at the same corresponding daily dose. Comparisons of the pharmacokinetic parameters AUC, Cmax, Cmin, and tmax at steady state for the two dosage forms demonstrated definitively the bioequivalence of carbamazepine OROS with Tegretol commercial tablet over a 24-h treatment interval. PMID- 1421051 TI - Applicability of teicoplanin dosage adjustment guidelines for renally impaired patients over the range of 3 to 30 mg kg-1. AB - The pharmacokinetics of teicoplanin were investigated in 13 subjects with various degrees of renal impairment using a randomized two-period crossover design; 11 subjects completed both periods. Doses of 3 and 30 mg kg-1 were administered as single dose, 60-min constant rate intravenous infusions. Blood samples were obtained over 28 days and urine was collected over 48 h. Serum and urine were analyzed using a microbiological assay. As previously observed in studies conducted in renally impaired subjects, teicoplanin total and renal clearance significantly decreased with decreasing creatinine clearance (p < 0.0001). However, for these parameters, no differences between doses were observed. Dosage adjustment guidelines for renally impaired patients are usually developed using the ratio of total clearance in renally impaired patients to the total clearance in patients with normal renal function. Since no dose-related differences existed in the relationship between teicoplanin total clearance and creatinine clearance, initial dosage adjustment guidelines for renally impaired patients developed at 3 or 30 mg kg-1 are applicable over the range of 3 to 30 mg kg-1. PMID- 1421052 TI - Disposition kinetics of 7,12-dimethylbenz(a)anthracene in rats. AB - One of the most potent carcinogens is 7,12-dimethylbenz(a)anthracene (7,12-DMBA), which is used routinely to conduct studies to evaluate carcinogen inhibitors. Its pharmacokinetics have not been reported in the literature. In view of its significant effects on drug metabolizing enzymes and clearance mechanisms, it is important to know its disposition characteristics. In this study, we monitored the disposition characteristics of 7,12-DMBA in rats as a function of dose range commonly used in carcinogenesis studies. A mean residence time of 40-55 min was observed; the total body clearance ranged from 8-13 l kg-1. No effect of dose was observed on the pharmacokinetic parameters. This suggests that the dose-dependent effects of 7,12-DMBA carcinogenesis are related to its transient disposition characteristics. PMID- 1421054 TI - Inappropriate inclusion of non-quantifiable plasma concentrations in the estimation of extent of absorption. PMID- 1421053 TI - Input rate-dependent stereoselective pharmacokinetics: enantiomeric oral bioavailability and blood concentration ratios after constant oral input. AB - A pharmacokinetic model and relevant equations were used to simulate the blood concentration ratio (Cratio) and oral bioavailability ratio (Fratio) of the two enantiomers of model racemic drugs after different oral input rates. The simulations were carried out for six metabolically eliminated racemic drugs with regard to differences between the two enantiomers in their metabolic maximum velocity (Vmax) and/or Michaelis-Menten constant (Km). Both Cratio and Fratio values were dependent on the oral input rate of the drugs, with the maximum sensitivity observed for input rates close to the Vmax of the enantiomers. However, at input rates substantially lower or higher than Vmax, the dependence of ratios to input rate was minimal. The profile of dependence of Cratio and Fratio on the input rate differed for the various modeled drugs and, in one case, input rate alteration lead to a reversal in the stereoselectivity of the ratios. Relevance of these findings with regard to alterations in the dose and/or formulation of racemic drugs is discussed. PMID- 1421055 TI - Neutrophil function in whole blood and after purification: changes in receptor expression, oxidase activity and responsiveness to cytokines. AB - Neutrophil function and plasma membrane receptor expression was measured in cell suspensions isolated by two separate procedures and in unfractionated whole blood. When cells were prepared by a combined dextran/ficoll procedure, their ability to generate reactive oxidants in response to fMet-Leu-Phe was greater than in corresponding cells isolated by a one-step procedure on Mono-Poly Resolving Medium (M-PRM). Cells prepared by both methods could be primed in vitro by rGM-CSF, but the priming ratio was greater in cells prepared by the latter method. The ability of neutrophils in whole blood to generate reactive oxidants in response to fMet-Leu-Phe was extremely low, but this was increased by more than 10 fold if the blood was pre-incubated with rGM-CSF. Similarly, expression of CD 11b and CD 16 was very low (or undetectable) in neutrophils in whole blood, but this was rapidly increased upon priming. Activation by PMA resulted in a down regulation of CD 16 expression as the receptor was shed from the cell surface. Neutrophils isolated by either the dextran/ficoll or the M-PRM method showed increased expression of receptors compared with those in whole blood, although this expression was lower in cells isolated by the latter method. These data indicate that the isolation procedures used to obtain purified neutrophils prime both receptor expression and oxidase function, although these effects are minimalised in isolation procedures using M-PRM. Furthermore, as CD 16 expression on neutrophils in whole blood is rapidly up-regulated during priming, it seems likely that, as for complement receptors, rapidly-mobilisable intracellular stores of this receptor exist. PMID- 1421057 TI - Evaluation of in vivo insulin action and glucose metabolism in milk-fed rats. AB - Milk diet has long been recommended in the management of gastrointestinal pathologies. Since milk feeding represents a high fat-low carbohydrate diet and it is acknowledged that insulin resistance is one of the consequences of high fat feeding, it is important to know whether or not chronic milk feeding leads to an impairment of the insulin-mediated glucose metabolism. To examine this question, adult female rats were given raw cow's milk (50% of total calories as lipids) for 18 days. They were compared to rats raised in parallel and fed the standard laboratory diet (15% of total calories as lipids). At the end of the 18 day period, body weight, daily caloric intake, basal plasma glucose and insulin levels in the milk-fed rats were similar to those in the control rats. In vivo insulin action was assessed with the euglycemichyperinsulinemic clamp technique in anesthetized animals. These studies were coupled with the 2-deoxyglucose technique allowing a measurement of glucose utilization by individual tissues. In the milk fed rats: 1) the basal rate of endogenous glucose production was significantly (p < 0.01) reduced (by 20%); 2) their hepatic glucose production was however normally suppressed by hyperinsulinemia; 3) their basal glucose utilization rate was significantly (p < 0.01) reduced (by 20%); 4) their glucose utilization rate by the whole-body mass or by individual tissues was normally increased by hyperinsulinemia. These results indicate that insulin action in adult rats is not grossly altered after chronic milk-feeding, at least under the present experimental conditions. PMID- 1421056 TI - Amino acid uptake regulation by cell growth in cultured hepatocytes isolated from fetal and adult rats. AB - Amino acid uptake mediated by system A was studied in cultured fetal and adult hepatocytes, subjected to growth stimulation by EGF and insulin, or to growth inhibition by high cell density. The mitogenic stimulation induced a strong transport increase only in fetal cells, while the cell density-dependent growth inhibition, probably mediated by molecules present on adult hepatocyte membranes, provoked the decrease of amino acid uptake only in the adult cells. The results indicate that the different modulation of amino acid transport by cell growth is dependent on the age and the differentiation stage of hepatocytes. PMID- 1421058 TI - In vitro secretion of transforming growth factor alpha (TGF-alpha): a comparison of the A431 cell line with three human oesophageal squamous cell carcinoma lines. AB - Transforming growth factor alpha (TGF-alpha) is a single chain polypeptide which exists in a variety of forms differing in molecular weight. These forms are variously present in normal and neoplastic cells. Of particular interest are TGF alpha's well-known mitogenic properties. The transition from a normal to a neoplastic cellular state results from signalling defects that may depend upon, inter alia, abnormal levels of expression and secretion of TGF-alpha. It is known that the secretion of TGF-alpha may be enhanced appreciably by agents such as phorbol 12-myristate 13-acetate (PMA), serum factors and epidermal growth factor (EGF). Here, we compare the efficacy of these three agents in the elevation of TGF-alpha secretion in the well studied A431 cell line with their previously undocumented efficacy in certain interesting, but little known, human oesophageal squamous cell carcinoma (SCC) lines. PMID- 1421059 TI - A domain of the alpha-subunit of rabbit phosphorylase kinase shows homologies with regions of rabbit alpha-tropomyosin, human EGF receptor, and the alpha chain of bovine S-100 protein. AB - Sequence comparison of the alpha-subunit of phosphorylase kinase with alpha tropomyosin revealed 32% identity, and 49% similarity, between the region of alpha-tropomyosin coded by exon 5 and a 39 amino acid segment of the kinase subunit. A subsequence of the alpha-subunit segment and a sequence overlapping the same alpha-subunit region are homologous with: (a) a region of the cytoplasmic domain of EGF receptor (50% identity) and (b) a Ca(2+)-binding domain of the alpha chain of S-100 protein (50% identity) respectively. Statistical analysis shows that these homologies are significant. The biological implication of the above similarities is discussed. PMID- 1421060 TI - Developmental regulation of potassium channels and the impact on neuronal differentiation. PMID- 1421061 TI - Axon terminal hyperexcitability seen in epileptogenesis in vitro. PMID- 1421062 TI - Glucose/insulin/potassium therapy: a reevaluation of myocardial benefits during cardiopulmonary bypass. PMID- 1421064 TI - Dobutamine increases heart rate more than epinephrine in patients recovering from aortocoronary bypass surgery. AB - To determine whether epinephrine might prove to be a cost-effective substitute for dobutamine, two 8-minute infusions of either epinephrine (10 and 30 ng/kg/min, n = 28) or dobutamine (2.5 and 5 micrograms/kg/min, n = 24) were administered to 52 patients recovering in the intensive care unit (ICU) after aortocoronary bypass (CABG) surgery. At the higher dose, both drugs significantly (P < .05) increased cardiac index (CI), epinephrine from 2.8 +/- 0.1 at baseline to 3.3 +/- 0.1 L/min/m2, and dobutamine from 3.2 +/- 0.1 at baseline to 4.1 +/- 0.2 L/min/m2. Epinephrine increased CI significantly less than dobutamine. Both drugs significantly increased stroke volume index (SVI), epinephrine from 32 +/- 1 at baseline to 36 +/- 1 mL/beat/m2, and dobutamine from 36 +/- 1 at baseline to 40 +/- 2 mL/beat/m2. At the higher dose, the effects of the two drugs on SVI were indistinguishable. On the other hand, while the higher dose of both drugs significantly increased heart rate (HR), epinephrine from 88 +/- 2 at baseline to 90 +/- 2 beats/min and dobutamine from 89 +/- 2 at baseline to 105 +/- 3 beats/min, the increase following the higher dose of dobutamine was significantly greater than that seen after epinephrine. Effects of the two drugs on mean arterial pressure, central venous pressure, pulmonary artery occlusion pressure, systemic vascular resistance, pulmonary vascular resistance, and left-ventricular stroke work did not significantly differ. Similar results were obtained in the subset of patients with baseline CI less than 3 L/min/m2 who more closely resembled patients who might acutely require inotropic drug administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421063 TI - Is calcium or ephedrine superior to placebo for emergence from cardiopulmonary bypass? AB - To determine whether ephedrine or CaCl2 improves hemodynamics in cardiac surgery patients emerging from cardiopulmonary bypass, three sequential doses of either CaCl2 (200 mg/dose; n = 12), ephedrine (5 mg/dose; n = 12), or placebo (n = 12) were administered in a prospective, randomized, double-blind fashion. Thermodilution volumetric catheters were used to calculate right ventricular (RV) volumes and ejection fraction. The first dose of ephedrine improved RV stroke volume from 57 +/- 3 to 63 +/- 4 mL/beat (P < 0.05) and ejection fraction from 44 +/- 2% to 49 +/- 2% (P < 0.05). Subsequent doses maintained this improvement but without further change. In contrast, placebo and CaCl2 had minimal effects on RV end-systolic volume, stroke volume, and ejection fraction. After the third injection of ephedrine, mean arterial pressure had significantly increased from 78 +/- 2 to 93 +/- 4 mmHg (P < 0.05) in contrast to insignificant increments with placebo and CaCl2. Serum ionized calcium increased by 6% to 8% after each CaCl2 bolus but remained stable in the ephedrine and placebo groups. CaCl2 failed to improve RV performance in mildly hypocalcemic patients during separation from cardiopulmonary bypass. In patients with normal preoperative ventricular function, ephedrine more effectively improved RV performance and arterial blood pressure than placebo or CaCl2, and is a suitable short-acting drug to assist separation from cardiopulmonary bypass. PMID- 1421065 TI - Amrinone and dobutamine as primary treatment of low cardiac output syndrome following coronary artery surgery: a comparison of their effects on hemodynamics and outcome. AB - This study was undertaken in order to compare the effectiveness of amrinone and dobutamine as primary treatment of a low cardiac output (CO) after coronary artery bypass graft (CABG) surgery. Thirty patients with preoperative left ventricular dysfunction participated in this open-label randomized study. Patients were included if they failed to separate from cardiopulmonary bypass (CPB) without inotropic support or if they had a cardiac index (CI) less than 2.4 L/min/m2 after CPB regardless of the blood pressure, in the presence of adequate filling pressures. The treatment objectives were to separate from CPB and achieve a CI > or = 2.4 L/min/m2 and a mean arterial pressure > or = 70 mmHg. Patients treated with amrinone received 0.75 mg/kg followed by 10 micrograms/kg/min; when the objectives were not achieved within five minutes, another 0.75 mg/kg was given. Patients treated with dobutamine received an initial infusion of 5 micrograms/kg/min increased stepwise to 15 micrograms/kg/min if necessary. Eleven of 15 amrinone versus 6 of 15 dobutamine patients achieved the predefined treatment objectives with the test drug alone (P = NS). Comparisons of hemodynamics in patients treated solely with amrinone (n = 7) or dobutamine (n = 6) after CPB showed no significant differences between the treatment groups. The incidence of myocardial ischemia as detected by Holter monitor was 36% with amrinone and 33% with dobutamine. Two patients suffered ventricular fibrillation and two had significant supraventricular tachyarrhythmias (heart rate > 130/min) during treatment with dobutamine alone, whereas no significant arrhythmias occurred in the amrinone group (P = NS). Six dobutamine patients (40%) had postoperative myocardial infarction (MI) as opposed to none among the amrinone patients (P = 0.017). These results indicate that amrinone compares favorably with dobutamine as a primary treatment of low CO after CABG. Further study in a larger number of patients will be required in order to determine if the lower incidence of MI in the amrinone group was due to the treatment drug. PMID- 1421066 TI - Intravenous milrinone following cardiac surgery: I. Effects of bolus infusion followed by variable dose maintenance infusion. The European Milrinone Multicentre Trial Group. AB - The hemodynamic and adverse effects of intravenous milrinone were studied in 99 adult patients (66 men) following elective myocardial revascularization, mitral and/or aortic valve surgery. All patients had a low cardiac output (cardiac index [CI] mean 1.93, range, 1.11 to 2.5 L/min/m2) despite adequate cardiac filling pressure (mean pulmonary capillary wedge pressure [PCWP] 11.5 mmHg, range, 8 to 20 mmHg). Following a period of baseline stability (mean 17.8 minutes, range, 10 to 50 minutes), patients received a bolus infusion of 50 micrograms/kg over 10 minutes. A continuous maintenance infusion of 0.375 (low), 0.5 (mid) or 0.75 (high) micrograms/kg/min was administered for a minimum of 12 hours. Patients were allocated to each dosage group sequentially, not randomly. Hemodynamic measurements were made before the start of milrinone and 15 minutes after the bolus infusion. Further measurements were made at 30, 45, and 60 minutes, and at 3, 6, and 12 hours after the start of treatment. Measurements were also made at 2 and 4 hours after treatment was stopped. The bolus infusion caused significant increases in CI, heart rate (HR), and stroke index (SI), (P < 0.001), and significant falls in PCWP, right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), mean arterial pressure (MAP), and systemic vascular resistance (SVR) (P < 0.001). These effects were maintained to a significant degree by each of the three maintenance infusion regimens, although the pulmonary vasodilator effects appeared less predictable and more dose dependent. Eighteen patients (19%) had arrhythmias; 16 of these were judged not to be serious events. Two were deemed serious; these were both episodes of fast atrial fibrillation (AF).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421067 TI - Intravenous milrinone following cardiac surgery: II. Influence of baseline hemodynamics and patient factors on therapeutic response. The European Milrinone Multicentre Trial Group. AB - Further analysis of the data from 99 adult patients who received an intravenous infusion of milrinone following elective cardiac surgery was done. All patients received a bolus infusion of 50 micrograms/kg over 10 minutes, followed by a maintenance infusion of either 0.375, 0.5 or 0.75 microgram/kg/min for a period of 12 hours. Hemodynamic measurements were made after the bolus infusion (15 minutes), and then after 30, 45, and 60 minutes at 3, 6, and 12 hours, and 4 hours after treatment was stopped. The following was found: (1) pretreatment cardiac index (CI) affected the response to treatment. Patients with a low CI (1.59 L/min/m2) had a 54% increase after the bolus infusion compared to a 27% increase in patients with a higher pretreatment value (2.2 L/min/m2) (P < 0.05); (2) patients with a high resting level of pulmonary vascular resistance (PVR > 200 dynes.sec.cm-5) had a greater response to treatment (26% fall in PVR) than the remainder (9% fall in PVR) after 60 minutes; (3) patients with a low pretreatment mean arterial pressure (MAP) (n = 17, MAP 64 mmMg, range, 52 to 70) showed no fall in MAP following treatment, but showed a significant increase in CI (+55%). A good therapeutic response was found that was similar in patients undergoing valve replacement surgery or coronary artery bypass graft surgery, and in patients in sinus rhythm or atrial fibrillation before treatment. It is concluded that the therapeutic response to intravenous milrinone following cardiac surgery is partially determined by pretreatment hemodynamics. PMID- 1421068 TI - Left ventricular filling as assessed by pulsed Doppler echocardiography after coronary artery bypass grafting. AB - Diastolic filling of the left ventricle, as assessed by transesophageal pulsed Doppler echocardiography during and in the early phase following coronary artery bypass grafting, was investigated in nine patients without valvular disease or left ventricular hypertrophy. The ratio between the maximal heights of the early diastolic flow-velocity peak and the late (atrial) diastolic flow-velocity peak, the E:A ratio, and also the deceleration time of the early peak were calculated as indices of left ventricular filling. The E:A ratio decreased from 1.01 +/- 0.06 after induction of anesthesia to 0.46 +/- 0.06 on arrival in the intensive care unit (ICU). The E:A ratio then increased and reached 0.87 +/- 0.08 after 6 hours in the ICU. This increase in E:A ratio in the ICU was due to an increasing peak velocity of the E wave. The deceleration time decreased after surgery and increased from 111 +/- 25 to 145 +/- 12 milliseconds in the ICU. Pulsed Doppler indices of diastolic filling are known to be altered by changes in hemodynamic parameters, to be load-dependent, and to vary with heart rate. In the ICU, pulmonary capillary wedge pressure remained unchanged, heart rate decreased by approximately 12%, and systemic vascular resistance decreased by approximately 40%. The changes in hemodynamic parameters could have affected the E:A ratio, but it is unlikely that they could explain the marked increase in the E:A ratio that occurred in the ICU. The results, therefore, imply the presence of impaired diastolic filling immediately after cardiopulmonary bypass with gradual, but not complete, recovery during the first 6 hours in the ICU. PMID- 1421069 TI - Left ventricular regional function and relaxation: effects of inotropic stimulation. AB - The effects of increasing doses of two inotropes, isoproterenol and calcium chloride (CaCl2), on left ventricular regional myocardial function and isovolumic relaxation were studied in six anesthetized sheep. After baseline data, CaCl2 was given as intravenous boluses to yield doses of 10 mg/kg, 20 mg/kg, 40 mg/kg, 80 mg/kg, and 160 mg/kg. After a second series of baseline data were obtained, constant infusions of isoproterenol were begun with doses of 0.025 micrograms/kg/min, 0.05 micrograms/kg/min, 0.1 micrograms/kg/min, 0.2 micrograms/kg/min, and 0.4 micrograms/kg/min. During each stage of the protocol with both inotropes, data were recorded during acute constriction of the descending thoracic aorta. Left ventricular relaxation was assessed by analysis of peak negative left ventricular (LV) dP/dt and the time constant of isovolumic left ventricular relaxation (Trelax). Regional myocardial function showed little change in either apical or basal segments until high doses of the inotropes. Peak negative LV dP/dt significantly changed from baseline (775 +/- 60 mmHg/s) with 0.2 micrograms/kg/min (1780 +/- 400 mmHg/s, P < 0.05 v baseline) and 0.4 micrograms/kg/min (2,220 +/- 380 mmHg/s, P < 0.05 v baseline) of isoproterenol, and was unchanged by CaCl2. Trelax was significantly decreased by all doses of isoproterenol, whereas only one dose of CaCl2 decreased Trelax. Trelax was increased with afterloading and this effect was altered by isoproterenol. It is concluded that isoproterenol hastens, whereas CaCl2 does not alter, left ventricular relaxation. This may reflect beta-adrenergic modulation of calcium fluxes during isovolumic relaxation. PMID- 1421070 TI - Effect of prostaglandin E1 on myocardial contractility in dogs anesthetized with halothane: load-independent and noninvasive assessment using transesophageal echocardiography. AB - The presence of an inotropic action of prostaglandin E1 (PGE1) in vivo is controversial, and there are conflicting results obtained by various indices of myocardial contractility. In this study, a direct effect of PGE1 on contractility was investigated in dogs by use of a load-independent contractile index: left ventricular end-systolic wall stress (LVESWS) versus the velocity of circumferential fiber shortening with rate-corrected (Vcfc) relationship using transesophageal echocardiography (TEE). Hemodynamics, arterial blood gas, and TEE data were obtained before PGE1 infusion (control), and with a 10%, 20%, and 30% decrease in mean arterial pressure (MAP) following intravenous PGE1 administration. PGE1 infusion rates were 0.19 +/- 0.03 at 10%, 0.82 +/- 0.17 at 20%, and 2.32 +/- 0.36 micrograms/kg/min at a 30% decrease in MAP. Pulmonary capillary wedge pressure, systemic vascular resistance index, and left ventricular stroke work index significantly decreased, and heart rate, cardiac index, and stroke volume index were not significantly altered. Analysis of the TEE data showed LVESWS (index of afterload) significantly decreased from 92.0 +/- 11.2 g/cm2 to 72.7 +/- 7.8 at 10%, 59.3 +/- 7.8 at 20%, and 44.6 +/- 6.2 at a 30% decrease in MAP, and Vcfc significantly increased from 0.595 +/- 0.065 circ/sec of control value to 0.670 +/- 0.056 at 10%, 0.824 +/- 0.049 at 20%, and 0.939 +/- 0.070 at a 30% decrease in MAP. In the LVESWS versus Vcfc relationship, no significant difference could be detected between the control state and the 10%, 20%, and 30% decrease in MAP, and no inotropic effect was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421072 TI - Massive hyperkalemia during combined heart-lung transplantation: inadvertent contamination with modified Euro-Collins solution. PMID- 1421071 TI - Canine end-systolic pressure-length relationships: depressed by diltiazem, invalidated by ischemia. AB - This study was designed to determine whether the end-systolic pressure-length relationship (ESPLR) reflects changes in regional contractility during the imposition of graded ischemia, and whether it is modified by diltiazem during propofol anesthesia. Seven beagles were anesthetized and instrumented to measure left ventricular pressure and subendocardial segment lengths (sonomicrometry) in the region of the left anterior descending (LAD) and circumflex (LC) arteries. Afterload was increased by the tightening of a snare around the descending thoracic aorta. Pressure-length loops were constructed and the slope of the ESPLR and the x-axis intercept, Lo, were calculated. Graded ischemia of the apical myocardium only was accomplished by the tightening of a micrometer-controlled snare around the LAD to produce Critical Constriction (CC), Ischemia 1 and 2 (I1, I2), and Total Occlusion (TO). In the basal LC region, LAD ischemia had no effect on either the ESPLR slope or Lo. In contrast, the ESPLR slope in the LAD area was decreased by ischemia at I1 (-40%), increased at TO (+69%), and unchanged at CC and I2, and was reduced by diltiazem at CC and I2 (-31% and -36%, respectively). The LAD ESPLR Lo was increased by ischemia by 64% and 61% at I2, and 91% and 122% at TO, before and after diltiazem, respectively. In the LC region, diltiazem decreased systolic shortening and the ESPLR slope. These results indicate that diltiazem has negative inotropic properties in both ischemic and nonischemic areas. Also, Lo is not a constant and must always be redetermined for every intervention. In the absence of ischemia, the ESPLR may be a reliable measure of myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421073 TI - Use of somatostatin analog in the treatment of hypotension during bowel surgery. PMID- 1421074 TI - Severe bronchospasm following cardiopulmonary bypass in an asthmatic. PMID- 1421075 TI - Myocardial infarction during coronary artery bypass surgery. PMID- 1421076 TI - Pro: a cardiac anesthesia team should be responsible for providing emergency cardiac surgical care. PMID- 1421077 TI - Con: cardiac anesthesia and elitism: where does SIGMA end and ROA begin? PMID- 1421078 TI - Avoiding intra-arterial placement of the introducer sheath. PMID- 1421079 TI - Continuous, noninvasive blood pressure monitoring in the heart room. PMID- 1421080 TI - A simple "remote control" for an ultrasound imaging system. PMID- 1421081 TI - Suicide by interruption of immunosuppressive therapy. PMID- 1421082 TI - Brainstem Fos expression following acute unilateral labyrinthectomy in the rat. AB - Detection of Fos protein expression with a polyclonal antibody was used to identify brainstem neurons responding to acute (24 h) effects of a unilateral sodium arsanilate chemical labyrinthectomy in Long-Evans rats. Asymmetrical expression was apparent in the medial and inferior vestibular nuclei, the prepositus hypoglossi, the dorsolateral central gray, and the inferior olivary beta subnucleus. These data suggest different distributions of neural activation compared with previous electrophysiological and 2-deoxyglucose results. In addition, there was some Fos expression bilaterally in the olivary dorsomedial cell column, interstitial nucleus of Cajal and the Darkschewitsch nucleus. These results support the concept of multiple systems participating in vestibular compensation and further define some specific nuclei involved in the acute stage. PMID- 1421083 TI - Apomorphine disrupts odour-induced patterns of glomerular activation in the olfactory bulb. AB - The olfactory bulb of adult male rats stimulated with propionic acid vapours displays a characteristic focus of high metabolic activity in the dorso-medial glomeruli, as revealed by the 2-deoxyglucose (2DG) method. Injection of the dopaminergic agonist apomorphine (1.5 mg kg-1) prior to odour stimulation completely abolishes this selective pattern of glomerular activation, while the metabolic activity of other bulbar areas is not significantly altered. This effect is abolished by a previous injection of the dopamine antagonist haloperidol (0.1 mg kg-1). These observations emphasize the probable involvement of dopamine and dopamine receptors in the bulbar processing of olfactory information. PMID- 1421084 TI - Quantitative autoradiographic mapping of a novel serotonin receptor-5-HT1S. AB - The spinal cord distribution of a recently identified, high affinity 3H-5-HT binding site, the 5-HT1S receptor was studied employing quantitative autoradiography with microdensitometry. The laminar distribution and density of other high affinity 3H-5-HT binding sites present in rat spinal cord, 5-HT1A, 5 HT1B and 5-HT1C, was also determined. The greatest density of 5-HT1S receptors was found in the superficial dorsal horn laminae, the autonomic nuclei around the central canal and the ventral motor nuclei. Smaller, variable densities of 5-HT1S receptors were observed in other spinal cord regions. A similar spatial pattern of receptor density was observed for 5-HT1A, 5-HT1B and 5-HT1C receptors. The distribution of 5-HT1S receptors suggests functional modulation of somatosensory input to spinal cord as well as control of visceral and somatomotor activity. PMID- 1421086 TI - Fos and jun in rat central amygdaloid nucleus and paraventricular nucleus after stress. AB - The present paper describes the effect of capsaicin-induced stressful stimulus on the expression of immediate early genes (IEGs) c-fos, c-jun, junB and junD in the hypothalamic paraventricular nucleus (PVN) and the central amygdaloid nucleus (ACe) using in situ hybridization. Stress caused an intense expression of c-fos, c-jun and junB especially in the PVN and ACe and also a clear induction of junD was observed in the PVN. This suggests that the PVN and the ACe are two major targets of stress in the brain. The intense expression of the IEGs in the ACe and PVN suggests that stress may affect neurotransmitter gene expression through Fos and Jun proteins in both these nuclei. PMID- 1421085 TI - Nitric oxide mediates Fos expression in the spinal cord induced by mechanical noxious stimulation. AB - Immunocytochemical localization of Fos protein was used to analyze the involvement of nitric oxide (NO) in the expression of Fos in the spinal cord, induced by mechanical noxious stimulation (NS). Mechanical NS was applied to the left hindpaw 30 minutes after intrathecal administration of the NO synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) and the resulting Fos expression in the spinal cord dorsal horn was compared with that obtained in rats exposed only to the mechanical NS. Pretreatment with L-NAME but not its stereoisomer N omega-nitro-D-arginine methyl ester (D-NAME), produced a dose dependent suppression of Fos expression induced by mechanical noxious stimulation. These results indicate that NO modulates the expression of Fos in the dorsal horn induced by mechanical noxious stimulation and further support the hypothesis that NO is involved in nociceptive events occurring in the spinal cord in response to a peripheral noxious stimulus. PMID- 1421087 TI - Decortication and striatal mRNA: increases of mRNA for fibronectin, but not of NCAM or alpha-1 tubulin. AB - Ipsilateral frontal cortex lesions damaged the corticostriatal input. Northern hybridization analysis showed increases in fibronectin (FN) mRNA, but not changes in mRNA for neural cell adhesion molecule (NCAM), neuro-filament-68 (NF-68) or alpha-tubulin (alpha-1T) 72 h post-lesion. In situ hybridization resolved a different spatial-temporal distribution. The superficial cell layer beneath the wound cavity showed transient elevations of FN mRNA that peaked at 72 h post lesion. However, in the ipsilateral striatum, FN mRNA was maximal at later times than in the wound cavity, at 240 h post-lesion. Changes in NCAM and alpha-tubulin mRNAs in response to decortication occur only around the wound cavity but not in the deafferentated striatum. The different time courses of mRNA revealed by Northern blot analysis and in situ hybridization are most probably due to contamination of the ipsilateral striatum at dissection with superficial tissue adjacent to the wound cavity. These results suggest that cellular responses to ipsilateral decortication consist of two phases: (i) a wound healing process; and (ii) striatal responses to deafferentation. PMID- 1421088 TI - Different distributions of dystrophin and related proteins at nerve-muscle junctions. AB - The distributions of dystrophin, 'dystrophin-related protein' (DRP) and beta spectrin were compared with that of acetylcholine receptors (AChRs) at rat nerve muscle junctions (NMJs) using immunofluorescence techniques. In sections, monoclonal antibodies (MAbs) to dystrophin and beta-spectrin labelled the entire sarcolemma but were concentrated at the NMJs while those to DRP labelled only NMJs. In permeabilized muscle fibres, DRP was precisely co-localized with the AChRs, whereas the zone of high density labelling of dystrophin and beta-spectrin extended 0.3-0.4 microns beyond the AChRs. Within the NMJ, the labelling of DRP appeared as a series of interconnecting lines similar to that of AChRs. However, labelling of dystrophin and beta-spectrin was consistently more punctate. These data suggest DRP is more closely associated with AChRs than are dystrophin or beta-spectrin. PMID- 1421089 TI - Oncostatin M regulates VIP expression in a human neuroblastoma cell line. AB - Oncostatin-M (OM), a recently described glycoprotein cytokine, is structurally and functionally related to cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) and ciliary neurotrophic factor (CNTF). To determine whether OM, like CDF/LIF and CNTF, possesses trophic or differentiative functions for neurons we examined the effects of recombinant human OM on ciliary neuron survival and neurotransmitter expression in sympathetic neurons. Like CDF/LIF, but in contrast to CNTF, OM had no effect on ciliary neuronal survival at any concentration tested. OM produced small but reproducible increases in choline acetyl transferase (ChAT) activity and vasoactive intestinal peptide (VIP) levels in rat sympathetic neuron cultures, but this effect was significantly less than that of CNTF or CDF/LIF. To determine if human OM would elicit a more robust response from human cells, we utilized a human neuroblastoma cell line, NBFL, that responds to CNTF and CDF/LIF by altering vasoactive intestinal peptide (VIP) levels. OM specifically elevated VIP and c-fos mRNA levels in NBFL cells and was as potent as CDF/LIF in this assay. Our data provides evidence that OM acts on neurons and identifies a neural cell line responsive to OM, CNTF, CDF/LIF. PMID- 1421090 TI - Wisteria floribunda agglutinin-labelled nets surround parvalbumin-containing neurons. AB - Net-like structures surrounding several types of neurones contain glycoconjugates which are detectable by lectins specific for N-acetylgalactosamine. Wisteria floribunda agglutinin (WFA) was introduced as a further marker for the visualization of such perineuronal nets, which were also revealed in regions of the rat brain where these structures could not be clearly demonstrated using other lectins. The WFA-labelled perineuronal nets resembled in detail those which could be visualized using Vicia villosa agglutinin, colloidal iron or hyaluronectin as markers. Furthermore, WFA-stained perineuronal net components appeared to be similar to proteoglycan-immunoreactive structures. Dual-peroxidase experiments and fluorescence double labelling demonstrated that WFA-binding structures frequently ensheath GABAergic neurons containing the calcium-binding protein parvalbumin in the areas investigated. PMID- 1421091 TI - Bicommissural neurones in the cerebral cortex of developing hamsters. AB - The trajectory, developmental time course, and origin of callosal fibres that recross through the anterior commissure were studied in developing hamsters, using carbocyanines in fixed brains on different ages. The bicommissural fibres were found in hamsters from E15 through P7, but disappeared after P7. By double labelling it was found that the neurones of origin of these bicommissural fibres were located in the lateral cortex within the region where the callosal zone of origin overlaps that of the anterior commissure. From these experiments, it was concluded that the axons of a group of cells in the lateral cortex of developing rodents are branched and grow transiently through both the callosum and the anterior commissure. PMID- 1421092 TI - Developmental changes of EAA metabotropic receptor activity in rat cerebellum. AB - The potency but not the efficacy of t-ACPD stimulation of phosphatydil inositide hydrolysis changes in developing rat cerebellum. This suggests that the excitatory amino-acid-stimulated metabotropic receptors and/or their coupling are ontogenically regulated. In this, cerebellum differs from other CNS regions where only efficacy changes were described. Differently from hippocampus, the t-ACPD effect, at all ages, is independent of the activation of the NMDA receptor. PMID- 1421093 TI - A transient immunoglobulin-like reactivity in the developing cerebral cortex of rodents. AB - Species-specific antisera against rat or mouse immunoglobulins, such as the commercial ones currently used as secondary antibodies in immunohistochemistry, revealed an intense, developmentally regulated immunostaining of the cerebral cortex in the homospecific rodent species. The immunostaining showed evident anatomical restrictions, favouring the subplate in prenatal animals. In Western blots, the antisera recognized the protein moiety of a 93 kDa glycoprotein. Both tissue and Western blot immunostaining were completely prevented by preadsorption of the antisera with the corresponding homospecific immunoglobulin. The present results show that a novel molecule, related to immunoglobulins, is transiently expressed in the developing cerebral cortex of rodents, and stress the need for exquisite controls in immunohistochemical studies. PMID- 1421094 TI - Neurotrophin-induced trk receptor phosphorylation and cholinergic neuron response in primary cultures of embryonic rat brain neurons. AB - Tyrosine phosphorylation of trk type neurotrophin receptors in primary cultures of embryonic rat brain cells was studied by immunoprecipitation and immunoblotting. In cultures containing basal forebrain cholinergic neurons, but not in cultures of cerebral cortex, nerve growth factor (NGF) treatment for 4 min induced tyrosine phosphorylation of trk family proteins. Stimulation with brain derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3), resulted in a very robust phosphorylation signal in basal forebrain and cortical cultures, suggesting actions of these neurotrophins not only on cholinergic cells but probably on most embryonic brain neurons. Trk tyrosine phosphorylation was completely abolished by 5 microM K-252b. Inhibition was rapid, being evident by 30 s following addition of the drug. Corresponding stimulatory and inhibitory effects were seen for phospholipase-C gamma 1 (PLC gamma 1) and extracellular signal-regulated kinase 1 (Erk1), two enzymes involved in second messenger mechanisms. Our findings indicate involvement of trk receptor activation in the NGF response of basal forebrain cholinergic cells and provide evidence for widespread presence of BDNF and NT-3 responsive neurons in the embryonic brain. PMID- 1421095 TI - Muscarinic M3 receptors inhibit a leak conductance in rat corticocallosal neurons. AB - Acetylcholine, acting on muscarinic receptors, has a powerful modulatory effect on neurons in the cerebral cortex. Recent evidence that cortical tissue contains at least four different muscarinic receptor subtypes having different pharmacological properties indicates the value of new investigations of the receptor subtypes that mediate electrophysiological responses. Here we studied the ionic nature and pharmacology of the depolarizing response to acetylcholine in identified corticocallosal neurons in primary culture. This response is the result of a non-rectifying 'leak' K+ conductance which is reduced in the presence of acetylcholine. The relative sensitivity of this conductance change to the antagonists pirenzepine and 4-DAMP suggests that it is mediated by the M3 subtype of muscarinic receptor. PMID- 1421096 TI - Mannitol does not affect energy metabolism in forebrain ischemia. AB - Mannitol has a beneficial effect on ischemic injury following a short-duration forebrain ischemic insult in rats. Using the same animal model, we attempted to show that this effect of mannitol could be traced (via an improvement in cerebral blood flow) to a tempering of the collapse in the high-energy phosphates that occurs during the insult. A 10 min ischemic insult was induced by bilateral carotid artery occlusion followed by a reduction of the blood pressure to 50 mmHg through removal of blood via a tail catheter. 31P NMR spectroscopy was used to monitor the energy state and the pH prior to, during, and after the insult. The studies show that mannitol administered in doses of 0.25 g kg-1 or 1.0 g kg-1 prior to the insult has no significant effect on the high-energy phosphate levels or on the cerebral pH during ischemia, or on their post-ischemia recovery. PMID- 1421097 TI - Increased monoamine turnover in the subfornical organ area following body fluid depletion. AB - To clarify whether monoaminergic inputs to the subfornical organ (SFO) area participate in fluid regulatory systems, we examined the effects of body fluid depletion on monoamine turnover in the region of the SFO using microdialysis techniques in rats. An iso-osmotic reduction of fluid volume following subcutaneous treatment with polyethylene glycol (PEG) significantly increased dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the SFO area. 5-hydroxytryptamine (5-HT) in the SFO area could be detected after the PEG treatment, while 5-HT was undetectable before the treatment. The data imply that both dopaminergic and serotonergic systems in the SFO area may be involved in controlling body fluid balance. PMID- 1421099 TI - Ganglioside derivative LIGA20 reduces NMDA neurotoxicity in neonatal rat brain. AB - The semisynthetic ganglioside derivative LIGA20 (II3Neu5-AcGgOse4-2-d-erythro-1,3 dihydroxy-2-dichloro-ac eta mide-4-trans-octadacene) was found to be about ten times more potent than the natural ganglioside GM1 in protecting neurones in culture against glutamate toxicity. Here we show that, in vivo, LIGA20 attenuated toxicity of the glutamate receptor agonist N-methyl-D-aspartate (NMDA). In seven day-old rats NMDA was injected intracerebroventricularly, while LIGA20 or GM1 were administered subcutaneously. The loss in brain weight, five days following treatment, was used to estimate NMDA toxicity. Significant protection was observed with 2.5 mg kg-1 of LIGA20, while at least ten times this dose was needed for GM1, thus suggesting the superior in vivo pharmacological action of LIGA20. PMID- 1421098 TI - Requirement for macrophages in neuronal injury induced by HIV envelope protein gp120. AB - HIV-1-related neuronal injury may involve a complex web of viral proteins and cytokines, but neurons themselves are not infected. The HIV envelope protein gp120 has been shown to engender an early increase in neuronal free calcium followed by delayed excitotoxic-like damage, which is prevented by N-methyl-D aspartate (NMDA) antagonists. In the present study, we found that the injurious effects of gp120 on retinal ganglion cell neurons require the presence of macrophages in mixed neuronal glial cultures of postnatal retina. Within 24 hours of incubation, 20 pM gp120 injured nearly 40% of retinal ganglion cells in cultures containing macrophages and other glial cells, whereas no deleterious effects of gp120 were noted on retinal ganglion cells in cultures depleted of macrophages. Thus, the toxic effect of gp120 on neurons appears to be an indirect one, mediated by activation of macrophages and perhaps other glial cells. PMID- 1421100 TI - Dose-response of rt-PA and its combination with aspirin in a rat embolic stroke model. AB - The efficacy and safety of thrombolysis with different dose regimens of recombinant tissue plasminogen activator (rt-PA) and its combination with aspirin was tested in an embolic stroke model. In rats the carotid territory was embolized with a single clot formed in a polyethylene tube and washed with saline. Fifteen minutes after embolization 10 animals were treated with rt-PA 10 mg kg-1; 11 with 15 mg kg-1; 12 with 20 mg kg-1 and 9 with 10 mg kg-1 + 20 mg kg 1 aspirin and 34 animals with saline. Rt-PA 10 mg kg-1 reduced median infarct volume (in percent of the ipsilateral hemisphere volume) from 19.5 to 4.8; rt-PA 15 mg kg-1 to 2.0; rt-PA 20 mg kg-1 to 0.0, while rt-PA 10 mg kg-1 + aspirin resulted in a median infarct volume of 9.5%. Thrombolytic therapy significantly and dose dependently (p = 0.001) reduced the infarct volume, improved the presacrifice clinical score and increased (p = 0.02) angiographically verified reperfusion. There was no additional benefit of coadministration of aspirin. PMID- 1421101 TI - Evidence for an endogenous cholecystokininergic balance in social memory. AB - The cholecystokinin (CCK) peptide family is involved in a variety of physiological processes, including neurotransmission in the brain. Pharmacological responses to CCK are mediated through at least two receptor subtypes termed CCK-A and CCK-B. Studies with CCK agonists suggest a possible role for CCK in cognition. Using selective antagonists and a behavioural recognition test based on the olfactory discriminative capacities of rats, we found that endogenous CCK acting at CCK-A and CCK-B receptors modulates olfactory recognition positively and negatively, respectively. CCK-B receptor antagonists therefore have facilitatory potentialities on memory processes. PMID- 1421102 TI - Possible inspiratory off-switch neurones in the ventrolateral medulla of the cat. AB - The location and axonal projection of a type of respiratory neurones (termed bIE neurones), which show burst firing at the time of phase transition from inspiration to expiration, were studied in Nembutal-anaesthetized, paralysed and artificially ventilated cats. The bIE neurones showed maximum firing at the sharp decline of inspiratory activity. All of the bIE neurones tested projected to medullary respiration-related areas of the ventral respiratory group (VRG), the dorsal respiratory group (DRG), and the Botzinger complex (BOT). The bIE neurones were distributed in the dorso-medial border of the main assembly of respiratory neurones of the VRG and BOT. The possibility that these bIE neurones participate in inspiratory termination is discussed. PMID- 1421103 TI - Sulpiride anxiogenic-like effect inhibition by a D1 dopamine receptor antagonist. AB - The increased latency to explore a white compartment from a black one into which a mouse has been introduced, appears to be correlated with its anxiety level. In this test, the D2 specific dopamine receptor antagonist (+/-) sulpiride dose dependently (5-40) mg kg-1 i.p.) increased this latency. This effect was suppressed by the D1 specific dopamine receptor antagonist SCH 23390 (25 micrograms kg-1 s.c.) which intrinsically displayed an apparent anxiolytic effect. PMID- 1421105 TI - Slow and medium afterhyperpolarizations in maturing rat hippocampal CA1 neurones. AB - The postnatal evolution of the signals underlying the afterhyperpolarization (slow-AHP and medium-AHP) was studied in rat CA1 hippocampal neurones (P10-16, P17-23 and P greater than 26) using in vitro slices. Noradrenaline (NA) and signal subtraction were used to decompose the AHP (m-AHP and s-AHP). The amplitude of the s-AHP was found significant between P10-16 and P17-23 cells; the m-AHP showed no significant change. The time to peak of the s-AHP of the P greater than 26 cells was found to be significantly different from the remaining groups; the m-AHP showed no significant change. The changes in waveform and amplitude of the AHP at this stage were found to be mainly due to the modifications of the slow-AHP. PMID- 1421104 TI - Apamin blocks the slow AHP in lamprey and delays termination of locomotor bursts. AB - The effects of apamin on the slow afterhyperpolarization (sAHP) in spinal neurones and on the frequency of rhythmic bursting during fictive locomotion were investigated in the lamprey spinal cord in vitro. Apamin, which is a selective blocker of a small conductance KCa channel responsible for the sAHP in many types of neurones, was also found to reduce the sAHP in lamprey neurones. The summation of the sAHP is considered to be an important burst terminating factor in the spinal locomotor network and thereby to regulate the frequency of fictive locomotion. In support of this view, apamin was found to reduce the frequency of rhythmic bursting during fictive locomotion induced by kainate and NMDA. Serotonin, which has previously been shown to reduce the sAHP and slow the rate of rhythmic bursting, may therefore act, at least in part, on apamin-sensitive KCa channels. PMID- 1421106 TI - Elevated gene expression in the red nucleus after spinal cord compression injury. AB - Since the mechanism of injury in the majority of human traumatic spinal cord injuries involves rapid cord compression due to bone displacement or fracture dislocation, we have used a compression injury model to examine the response of adult rat rubrospinal neurons to traumatic spinal cord injury. We have applied in situ hybridization techniques to examine levels of mRNA for cytoskeletal and growth-associated proteins. We report a population of magnocellular red nucleus neurons with elevated levels of T alpha 1 tubulin and GAP-43 up to four weeks post-lesion. In control animals, both probes had very low hybridization signals indistinguishable from background. These and other findings suggest that kinetic compression injuries of the adult spinal cord can result in regeneration associated gene expression in intrinsic CNS neurons. PMID- 1421107 TI - Potentiation of GABA-mediated currents by cAMP-dependent protein kinase. AB - Recent reports described a down-regulation of gamma-aminobutyric acid (GABA) receptor function in several types of central neurones by cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA). Surprisingly, we found that in cerebellar Purkinje cells (PCs) the membrane permeable-compound 8-bromo-cAMP (500 microM) induced a long-lasting potentiation of both, whole-cell current responses to bath-applied GABA and amplitudes of miniature inhibitory synaptic currents (mIPSCs). When dialyzing the PCs with the specific protein kinase inhibitor peptide (PKIP, 400 micrograms ml-1), the same manipulation failed to induce a potentiation. These results strongly suggest that, in contrast to its action in other types of neurones, activation of PKA up-regulates the GABAA receptor function in cerebellar PCs. PMID- 1421108 TI - Inhibition of nitric oxide synthesis impairs two different forms of learning. AB - Nitric oxide (NO), an intercellular messenger in the central nervous system of vertebrates, plays an important role in the establishment of synaptic plasticity. In order to investigate the role of NO and synaptic plasticity in learning, we injected rats and rabbits with the NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) prior to training on two tests of learning. Rats treated with L NAME were impaired in learning a spatial learning task, while rabbits given the NO synthase inhibitor demonstrated learning deficits in the conditioned eyeblink response. The results support the hypothesis that NO plays a critical role in acquisition of two different forms of learning. PMID- 1421109 TI - Specific hypothalamic neuropeptide Y variation with diet parameters in rats with food choice. AB - Neuropeptide Y (NPY) preferentially stimulates carbohydrate intake rather than fat intake but there is no information on the effects of food choice on the concentration of NPY in the brain. We measured brain NPY concentrations in male adult rats that had to choose between a high fat and a high carbohydrate diet or were fed a control diet for 2 weeks. In rats with food choice, energy intake increased (+17%). NPY levels increased in the parvocellular part (PVNp) of the PVN and decreased in the lateral hypothalamus and were significantly correlated with the carbohydrate-to-fat energy ratio but not with total energy intake. This suggests that hypothalamic NPY might be involved in food choice and that PVNp is important in the regulation of feeding behaviour by NPY. PMID- 1421110 TI - Gene expression in the geniculate induced by a nonphotic circadian phase shifting stimulus. AB - We examined the effect of a nonphotic stimulus (running in a novel wheel) on the induction of Fos-related proteins in the two well-established neural components of the circadian clock: the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) of the lateral geniculate complex. There was no induction of Fos immunoreactivity (IR) in the SCN, but the IGL showed distinct Fos IR in animals whose running levels were associated with maximal rhythm shifts. Induction of Fos immunoreactivity was greatest at circadian phases when wheel running induces phase shifts. This temporal and spatial specificity of Fos induction is evidence that the intergeniculate leaflet mediates nonphotic signals to the circadian clock. PMID- 1421111 TI - Evoked oscillatory cortical responses are dynamically coupled to peripheral stimuli. AB - We report that the response of neurons in rat somatosensory cortex to tactile stimulation consists of two components, a short-latency response and an oscillatory response, observable as up to 8 peaks in the post-stimulus-time histogram with interpeak intervals in the order of 100 ms (10 Hz). While the first component is always stimulus locked, the second component is strictly stimulus-locked only when elicited from the resting state: once started, the oscillations are only weakly affected by further stimulation. This implies generally that the question of stimulus locking of oscillatory response components is not a yes/no question. Instead, the concept of dynamic coupling is shown to adequately capture the different limit cases. We present a simple dynamic model that exemplifies this point. PMID- 1421112 TI - Perceptual correlates of massive cortical reorganization. AB - Following long-term deafferentation of one upper limb in adult primates, the cortical areas corresponding to that limb become responsive to stimuli applied to the face. To explore this phenomenon, we studied some patients after upper limb amputation. In patient VQ, stimuli applied to the lower face or 7 cm above the stump evoked precisely localized referred sensations in individual digits which were often modality specific. Similarly, in another patient, WK several complete somatotopic representations of the phantom limb were found, on the face, chest and axilla, indicating the emergence of such maps in regions remote from the stump. These effects may be a direct perceptual correlate of the physiological observations of Merzenick et al (1984), Wall (1977) and Pons et al (1991). PMID- 1421113 TI - The differential effects of lateral midbrain lesions on the two phases of formalin pain. AB - Lesions were placed in the lateral midbrain (LM) to determine the effects of disruption of paleo- and neospinothalamic systems, at the level of the midbrain, on the biphasic tonic pain response induced by formalin. During the first phase of formalin pain, subjects with LM lesions exhibited significantly less pain responding than did unoperated controls or subjects with lesions at another site, the habenula. During the second phase, there were no significant differences in pain responding among the three groups. The results suggest that the two phases are mediated by different neural substrates and specifically that Phase 2 appears to involve either neural substrates caudal to our LM lesions or sites rostral to the lesions but accessible via a more medial path. PMID- 1421114 TI - Atropine and naloxone sensitive stimulation produced analgesia from pretectal nucleus in rat. AB - Mild and brief electrical stimulation of sites in the pretectal nucleus (PTN) of rats evoked potent analgesia of long duration, without significant aversions and was unassociated with motor deficit. The present study has analysed effects of opioidergic and cholinergic neurotransmitter antagonists administered intracerebroventricularly (i.c.v.) on this analgesia. Pretreatment either with naloxone or atropine sulphate both in doses of 30 and 50 micrograms each, respectively i.c.v., 10 min prior to subsequent pretectal stimulation, significantly attenuated the increase in tailflick latency. The antagonism of pretectal stimulation produced analgesia (PSPA) by naloxone and atropine, raises the possibility of involvement of both endogenous opioids and cholinergic mechanisms in pretectal analgesia. PMID- 1421115 TI - Behavioral correlates of action potentials recorded chronically inside the Cone Electrode. AB - Long-term recording of stable action potentials with a new electrode configuration has been achieved for up to 15 months in monkeys. Action potentials are separated from the continuous multi-unit recordings made between two wires inside a glass open ended cone implanted in the motor cortex. Neural tissue is induced to grow into the glass cone by autologous sciatic nerve placed inside prior to implantation. Data presented here show that behavioral correlates of neural activity are related to flexion and extension movements of the contralateral hand and digits. These data suggest that this electrode can be used in both basic and applied studies. PMID- 1421116 TI - Evaluations of ventral pallidal dopamine receptor activation in behaving rats. AB - Recent evidence justifies the inclusion of the ventral pallidum/substantia innominata (VP) into the category of dopaminoceptive brain regions. Since the VP is known to mediate both cognitive and motoric processes, the present study employed intracerebral microinjections of dopamine directly into the VP of rats to determine if the catecholamine influences these processes. Dopamine concentrations of up to 10 micrograms were ineffectual in altering performance parameters in a working memory task. However, concentrations as low as 0.01 micrograms increased locomotion in an open field. The magnitude of this response was related to the dopamine dose injected and the effect was attenuated by systemic pretreatment with the dopaminergic antagonist, flupentixol. These studies suggest that dopamine neurotransmission at the level of the VP may be important in the locomotor functions attributed to ascending dopamine systems. PMID- 1421117 TI - SKPYMRFamide, a novel FMRFamide-related peptide in the snail Lymnaea stagnalis. AB - In Lymnaea stagnalis, three members of the FMRFamide peptide family have been chemically identified in the central nervous system, and other members of the family are predicted by cDNA studies. The present study demonstrates the occurrence of even more FMRFamide-related peptides in this species by identifying a novel member of this family. The peptide was purified from brain extracts by three different HPLC steps. Its amino acid sequence has been determined as Ser Lys-Pro-Tyr-Met-Arg-Phe-amide (SKPYMRFamide). PMID- 1421118 TI - Fibronectin staining detects micro-organisms in aged and Alzheimer's disease brain. AB - Filamentous, fibronectin-immunopositive structures, previously described in Alzheimer's disease and control brains were negative for neuronal, glial, and macrophage markers. The present study sought to determine the nature of these entities and to further characterize their morphology, immunoreactivity and distribution between neuropathologies. Ultrastructural analysis shows these formations to be filamentous micro-organisms, which may belong to the actinomycetes. Immunohistochemistry for the cell-stress protein ubiquitin is consistently positive in these organisms. They are also present in Down's syndrome, dementia pugilistica, amyotrophic lateral sclerosis with dementia, and Parkinson's disease. The pattern of tissue distribution implies a pre-mortem invasion of the brain, and, as the micro-organism is present at a four to five fold higher frequency in Alzheimer's disease, it may act pathogenically in this dementing illness. PMID- 1421119 TI - Expression of neuronal markers in the so-called ENU-induced schwannomas. AB - The present data show that the so-called ENU-induced malignant schwannomas express neuronal markers. This finding supports the hypothesis that a population of tumor cells in these neoplasms are neuroblastic in nature, and suggests the classification of ENU-induced schwannomas as primitive neuroectodermal tumors. PMID- 1421120 TI - Drug interactions represented by high resolution computer graphics. AB - The amount of backward walking induced in mice by co-administration of clenbuterol, a beta-adrenoceptor agonist and putative antidepressant, and the benzodiazepine chlordiazepoxide was plotted as a three-dimensional surface, using modified Uniras software. The surface was compared with the theoretical surface to be expected if the interactions between the two drugs were merely additive. The difference between the theoretical and the obtained surfaces was plotted and a functional representation of statistical variability was 'draped' over the difference model. The computer methods can be applied to small amounts of irregularly distributed data, and results are apparent from simple inspection, e.g. the highest peak of backward walking is also the most reliable statistically. The technique is useful for both laboratory and clinical studies. PMID- 1421121 TI - Effects of a metabotropic glutamate agonist, trans-ACPD, on cortical epileptiform activity. AB - The effect of the metabotropic glutamate receptor agonist trans-1-amino 1,3,cyclopentanedicarboxylic acid (trans-ACPD) on epileptiform activity induced in rat neocortical slices by exposure to Mg(2+)-free medium was examined. Trans ACPD dose dependently (10-200 microM) decreased the frequency of spontaneous epileptiform events whilst increasing both the duration of afterpotentials and the number of afterbursts associated with single events. This effect on afterpotentials and afterbursting was particularly pronounced in 14-17 day-old rats and was blocked by the sigma ligand ditolyguanidine (DTG) 10 microM. The putative metabotropic glutamate receptor antagonist L-AP3 did not antagonise the actions of trans-ACPD. The results suggest a role for metabotropic glutamate receptors in epilepsy, possibly in the transition from interictal to ictal activity. PMID- 1421122 TI - 5-HT response of rat hippocampal pyramidal cell bodies. AB - Serotonin (5-HT) responses of pyramidal neurones freshly dissociated from rat ventral hippocampal CA1 region were investigated by using nystatin-perforated whole-cell recording. These dissociated neurones lack most of the dendrites and axons. Application of nanomolar concentrations of 5-HT induced outward current with an increase of membrane conductance at a holding potential (VH) of -40 mV. The current was mimicked by alpha-methyl-5-HT (5-HT2 receptor family agonist), but not by 8-OH-DPAT (5-HT1 receptor family agonist). Ketanserin (5-HT2 receptor family antagonist) and spiperone (5-HT1A and 5-HT2 receptor family antagonist) blocked the current in a concentration dependent manner. These results suggests that 5-HT-induced outward current is mediated by the activation of 5-HT2 receptor family in the cell bodies of hippocampal pyramidal neurones. PMID- 1421123 TI - The effects of orally active enkephalinase inhibitors on morphine withdrawal syndrome. AB - Considerable evidence has accumulated to suggest that intracerebroventricular administration of enkephalinase inhibitors, which do not penetrate the blood brain barrier, significantly attenuates opioid withdrawal syndrome. Therefore, the aim of this study was to examine the effect of intraperitoneal (i.p.) administration of orally active enkephalinase inhibitors, acetorphan (2.5-20 mg kg-1) and SCH 34826 (15-120 mg kg-1). These drugs significantly decreased the severity of the naloxone precipitated withdrawal syndrome in morphine dependent rats and mice. It therefore appears that these orally active enkephalinase inhibitors are promising tools in studying modulation of opioid dependence phenomena. PMID- 1421124 TI - Effect of nitecapone and clorgyline, given intracerebro-ventricularly on L-dopa metabolism in the rat brain. AB - A new COMT inhibitor, nitecapone (OR-462) or clorgyline, a MAO-A inhibitor, was infused into the 3rd brain ventricle (i.c.v.) of conscious male rats. None of the enzyme inhibitors given alone alter hypothalamic or striatal levels of L-dopa, dopamine or their metabolites. Most of the rats were pretreated with levodopa/carbidopa (LD/CD, 15/30 mg kg-1 intraperitoneally). Now, the action of nitecapone is localized in the hypothalamus since homovanillic acid (HVA) is decreased there, not in the striatum. The levels of 3-O-methyldopa (3-OMD) are not changed in either brain region, suggesting a lack of the peripheral leakage of nitecapone. Clorgyline (3 and 10 micrograms rat-1) elevates hypothalamic and dopamine levels. Nitecapone and clorgyline decrease prolactin (PRL) levels below those reduced by LD/CD treatment. PMID- 1421125 TI - Philanthotoxin-343 blocks long-term potentiation in rat hippocampus. AB - The effects of extracellularly-applied synthetic philanthotoxin-343 (PhTX-343) on transmission and long-term potentiation (LTP) at Schaffer-collateral/commissural CA1 synapses were investigated. PhTX-343 was ineffective in antagonizing CA1 field-EPSPs mediated by AMPA/kainate receptors. However, when a micromolar concentration of the toxin was present during tetanization, the induction of LTP was suppressed. In contrast, when PhTX-343 was applied either immediately after or long after tetanization no effect on LTP could be found. It appears that the synaptic, non-NMDA receptors of the CA1-region are insensitive to PhTX-343. Suppression of LTP induction could result from antagonism of postsynaptic NMDA receptors, but the results do not rule out other possibilities such as presynaptic block. PMID- 1421127 TI - Reduction of A1 adenosine receptors in cortex, hippocampus and cerebellum in ageing mouse brain. AB - Age related changes in A1 adenosine receptor binding were investigated in mouse brain using the selective agonist, [3H]-cyclohexyladenosine ([3H]CHA). In the cortex, hippocampus and cerebellum of aged mice (28 months old), a significant decrease of about 44%, 50% and 12%, respectively, in [3H]CHA binding compared to young animals (3 months old) was observed. According to the Scatchard analysis of the binding data in the cortex, this decrease was due to a receptor density reduction and not to a Kd change. Since the weight and protein content of each tissue tested did not differ significantly between the old and the young animals, our findings may be partly explained by specific reductions of A1 receptors rather than a general cell degeneration in old age. PMID- 1421126 TI - beta-Amyloid increased neuronal susceptibility to injury by glucose deprivation. PMID- 1421128 TI - Early functional glutamate receptors in acutely dissociated embryonic raphe cells. AB - We report for the first time, modulation of cytosolic calcium in response to glutamate and specific glutamate receptor agonists in early embryonic rat brain cells (raphe cells taken at gestation days 13 or 14). Metabotropic as well as ionotropic agonists were effective. Cells responding to kainic acid were particularly prominent in caudal raphe. We used very short post-plating delays (2 to 6 h); it may therefore be assumed that functional receptors already exist in the intact embryonic brain by gestation day 13. Since many developmental processes are influenced by cytosolic calcium modulation, glutamate receptors may play a key role in brain development, well before the extensively studied postnatal peak in receptor density. PMID- 1421129 TI - A novel method to analyse response patterns of taste neurons by artificial neural networks. AB - Despite several notions on the gustatory code proposed over three decades, investigators have not yet reached a consensus. This paper describes a new approach to analyse gustatory neural activities. Three-layer neural networks were trained by the back-propagation learning algorithm, to classify the neural response patterns to four basic taste qualities. The discrimination by the trained networks on taste qualities in the response patterns of rat chorda tympani fibres (CT) and cortical taste neurons (CN) was consistent both with the correlation analysis and with behavioural experiments. By examining the connection weights of each neuron, some input neurons representing CN were 'pruned' without deteriorating the ability of the network to discriminate taste. This characteristic of the network is contrary to a previous hypothesis, that taste neurons are of equal importance in the neural coding. PMID- 1421130 TI - Immunolocalization of two cytochrome P450 isozymes in rat nasal chemosensory tissue. AB - The NMa and NMb isoforms of cytochrome P450 enzymes are expressed in three nasal chemosensory organs: the olfactory, septal and vomeronasal mucosae. The NMa isoform is widely distributed throughout the nasal mucosa whereas the NMb isoform is present primarily in the chemosensory mucosae. The localization of cytochromes P450 demonstrates that sustentacular cells in the olfactory and septal epithelia, the mucus of the vomeronasal organ and the acinar cells of glands in the lamina propria of all three chemosensory systems engage in xenobiotic metabolism and participate in odorant/pheromone clearance, a perireceptor process associated with chemosensory transduction. PMID- 1421131 TI - Neutrophil-activating peptide-1/interleukin-8 mRNA is localized in rat hypothalamus and hippocampus. AB - Neutrophil-activating peptide-1/interleukin-8 (NAP-1/IL-8) is a cytokine synthesized by various cell types. In the immune system NAP-1/IL-8 is part of an immune cascade initiated by IL-1 production. NAP-1/IL-8 affects hypothalamic function and its production is suppressed by steroids. Therefore, it might be expected that NAP-1/IL-8 would be produced in brain areas involved in the control of the hypothalamic-pituitary-adrenocortical axis (HPA). NAP-1/IL-8 mRNA was localized by in situ hybridization in the paraventricular nucleus of the hypothalamus and hippocampus. Those areas also express the genes encoding interleukin-1-alpha (IL-1 alpha), IL-1 beta, IL-1 receptors, and IL-1 receptor antagonist (IL-1ra). This suggests that an immune cascade, which is well characterized in the immune system, may exist in brain, in areas of relevance to the regulation of stress-related neuroendocrine function. PMID- 1421132 TI - Treatment with excitatory amino acids or high K+ and NMDA receptors in cerebellar granule cells. AB - N-methyl-D-aspartate (NMDA) receptor activity was examined, in terms of 45Ca2+ influx, during the development of cerebellar granule cells grown under 'non trophic' [10 mM potassium (K10)] or 'trophic' conditions [25 mM potassium (K25), NMDA and kainate (KA)]. NMDA receptor activity increased sharply between 2 and 4 days in vitro (DIV) irrespective of growth conditions which upon further cultivation exerted a powerful influence, the NMDA response increasing progressively in K25 and NMDA grown cells, while remaining at a constant level in KA treated cells. In contrast, in K10 grown cells the NMDA response declined by 7 DIV to about 20% of the estimates in K25 at 9 DIV. Trophic conditions are, therefore, essential for the proper functional expression of NMDA receptors. PMID- 1421133 TI - Preparation for reaching: a PET study of the participating structures in the human brain. AB - The regional cerebral blood flow (rCBF) was measured as an indicator of regional metabolic activity with positron emission tomography (PET) in eight subjects who, after seeing a screen with seven targets prepared themselves with their eyes closed to reach these targets. The preparation phase was associated with increases of rCBF in the prefrontal cortex, several remote visual association areas in the parietal lobe, the supramarginal gyrus, the ventrolateral thalamus and the cerebellar vermis. During the course of learning the activations in the parietal visual areas, the supramarginal gyrus and the prefrontal cortex prevailed as a sign of the visual spatial information; its transformation being kept in working memory. The other activations vanished. No activations were seen in the motor cortices, indicating that reaching is a task which does not require substantial preparatory activity of motor cortices prior to the go signal. PMID- 1421134 TI - Atypical pyramidal cells in epileptic human cortex: CFLS and 3-D reconstructions. AB - Epileptic temporal cortices, removed from 3 patients with intractable partial epilepsy (IPE) during neurosurgery, were studied. Pyramidal neurons (40-50 per slice) in laminae III, V and white matter, were injected with lucifer yellow. Samples were examined in a confocal laser scanning microscope (Biorad 600) and individual cells scanned at 0.1-1 microns incremental levels. 2-D maximal linear projection was used for overview. Frames (50-60) of scanned neurons were transformed into 3-D volumes, using VoxelView software on a Silicone Graphics workstation and rotated. All samples contained neurons with duplicated apical dendrites, additional basal dendrites or were misplaced in a horizontal position in the white matter. The relation between these preliminary observations and the disease is discussed. PMID- 1421135 TI - beta-Amyloid induces neuritic dystrophy in vitro: similarities with Alzheimer pathology. AB - beta-Amyloid protein, the major component of neuritic plaques found in Alzheimer's disease, has been implicated as a potential contributor to the disease's progressive neuropathology. We report that within a two day exposure to aggregates of synthetic beta-amyloid peptide, the neurites of cultured rat hippocampal neurons adopt a dystrophic appearance. Observed morphological changes in the neurites include beading, fragmentation, terminal swelling and tortuous growth patterns. The degenerative changes are similar to those observed in neurites associated with neuritic plaques, suggesting that beta-amyloid may induce the neuritic abnormalities of Alzheimer neuropathology. PMID- 1421136 TI - Differential effects of deprenyl and MPTP on catecholamines and activity in BALB/c mice. AB - The present study examined the effects of deprenyl (1.5 mg kg-1) and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg kg-1) on dopamine (DA), norepinephrine (NE) and motor activity in BALB/c mice. Results indicate that pre treatment with deprenyl injections protected against MPTP's toxicity on DA, NE and motor function. However, if deprenyl was given 3 or 7 days after the MPTP injection (for 3 days in succession), it could not reverse MPTP's toxicity. However, if deprenyl was given for an extended period of 7 days, it reversed MPTP's toxicity on NE, but not on DA and behaviour. If deprenyl was given soon after MPTP each day for 10 days, it protected against MPTP's toxicity on DA and NE, but not on locomotor activity. These results suggest that only prior and repeated deprenyl injection has a satisfactory protective effect against MPTP's neurotoxicity. PMID- 1421138 TI - Specific in vitro synaptogenesis between identified Lymnaea and Helisoma neurons. AB - We tested the ability of identified neurons from two different families of pulmonate molluscs to form specific connections in vitro. The presynaptic neuron chosen for this study was the giant dopamine cell of Lymnaea stagnalis and Helisoma trivolvis which is known to synapse upon specific visceral and parietal ganglion neurons in both species. Here we show that the giant dopamine cells can reform specific connections in vitro on follower neurons from both species. Thus the mechanisms that determine synapse specificity are conserved between two different families of molluscs. PMID- 1421137 TI - Morphine differentially affects domoic acid and kainic acid toxicity in vivo. AB - The effect of systemic injections of morphine on behavioural toxicity and hippocampal (CA3 region) damage produced by both domoic and kainic acids was investigated in mice. Low doses of morphine (2.0 and 4.0 mg kg-1), but not higher doses, significantly antagonized the toxic response to a previously determined TD50 of domoic acid. By contrast, low doses of morphine had either minimal or no effect on the response to an equitoxic dose of kainic acid (TD50), but higher doses (6.0 and 8.0 mg kg-1) resulted in significant potentiation of kainate toxicity. These results provide the first evidence of a pharmacological dissociation between the mechanisms of domoic acid and kainic acid toxicity in vivo, suggesting that these two toxins produce behavioural and hippocampal toxicity via overlapping but non-identical mechanisms. PMID- 1421139 TI - Circadian rhythms of vasopressin content in the suprachiasmatic nucleus of the rat. AB - The suprachiasmatic nucleus (SCN) of the anterior hypothalamus contains a circadian pacemaker in mammals. We determined the circadian profiles of arginine vasopressin (AVP), a major peptide in the dorsomedial SCN, in rats under light dark (LD), constant dark (DD) and constant light (LL) conditions. Under LD conditions, AVP levels in the SCN showed circadian rhythmicity with a peak at early light phase and a broad trough during the dark phase. This rhythm in the AVP contents was maintained even after 14 days of free-running under DD conditions and 3 days under LL conditions. These circadian patterns of AVP are similar to those of somatostatin, another peptide in the dorsomedial SCN. This indicates a common mode of regulation for peptides in this subfield of the SCN. PMID- 1421140 TI - D600, a Ca2+ antagonist, prevents stimulation of nerve regeneration by magnetic fields. AB - We have found that regeneration of the rat sciatic nerve is stimulated if the rats are exposed to a 50 Hz sinusoidal magnetic field. In this study we investigated the effect of a Ca2+ antagonist, methoxyverapamil (D600) on this response. D600 was administered to the regenerating segment of the nerve via implanted osmotic minipumps. Magnetic field exposure increased regeneration distances in vehicle perfused nerves. This enhancement was blocked by perfusion with D600 at a concentration which alone failed to affect outgrowth of nerve fibres, lending support to the idea that Ca2+ fluxes could be involved in mediating the biological actions of magnetic fields. PMID- 1421141 TI - Site of initiation of replication of the ribosomal genes of pea (Pisum sativum) detected by two-dimensional gel electrophoresis. AB - The time course of replication of the 9 kb ribosomal DNA repeats of synchronized root cells of pea was followed by two-dimensional gel electrophoresis. The temporal order of appearance of single-stranded replication intermediates shows that replication begins within the subrepeats located in the intergenic spacer region about 1.5 kb downstream from the 3' end of the 25S gene. Hybridization to specific probes indicated that this location is identical to that established earlier by a different method. PMID- 1421142 TI - Biological activities of human interferon and 2'-5' oligoadenylates in plants. AB - Exogenous human interferon 2 (IFN) and 2'-5' oligoadenylates (2-5A) have been shown to cause at least a dual physiological effect in tobacco and wheat: (i) increased cytokinin activity and (ii) induced synthesis of numerous proteins, among which members of two groups of stress proteins have been identified, namely pathogenesis-related (PR) and heat shock (HS) proteins. These effects were observed only by low concentrations of these substances: IFN at 0.1-1 u/ml and 2 5A at 1-10 nM. PMID- 1421143 TI - The wheat mitochondrial genome contains an ORF showing sequence homology to the gene encoding the subunit 6 of the NADH-ubiquinone oxidoreductase. AB - A region of the mitochondrial (mt) DNA of wheat was studied because of its homology with other plant mtDNAs. Sequence analysis revealed an open reading frame encoding a polypeptide of 247 amino acids. Comparison of the sequence of the putative polypeptide with the protein sequence data of the Swiss-Prot library reveals homology with subunit 6 of the NADH-ubiquinone complex of mitochondria from Marchantia polymorpha, Podospora anserina, Chlamydomonas reinhardtii and of chloroplasts from M. polymorpha and Oryza sativa. No similarity was detected when compared with the subunit 6 of animal mitochondria, probably due to the rapid evolution of the sequence. A single 1.2 kb transcript appears in northern RNA blots. We found 15 edited sites of which only 13 give amino acid changes. This is the first report of a mt nad6 gene in higher plants. PMID- 1421144 TI - The organization of the prosystemin gene. AB - The organization of the gene encoding tomato prosystemin, a 200 amino acid protein precursor of the 18 amino acid polypeptide inducer of proteinase inhibitor synthesis in tomato and potato plants, is reported. The prosystemin sequence reveals that the gene, which is composed of five homologous pairs of exons plus a non-homologous exon at the C-terminus containing the systemin sequence, has evolved by several gene duplication-elongation events from a much smaller ancestral gene. The nucleotide and amino acid sequence homologies among the exons suggest that a small ancestral gene was duplicated to form at least two tandem repeats, followed by subsequent duplication-elongation events that resulted in five tandemly repeated nucleotide sequences and three duplicated amino acid sequence elements. Since the systemin nucleotide or amino acid sequence was not duplicated, it was either not part of the gene duplication elongation events or its coding region evolved separately and may even have been added to the tandemly repeated part of the gene at a later time. PMID- 1421145 TI - Salt stress alters A/T-rich DNA-binding factor interactions within the phosphoenolpyruvate carboxylase promoter from Mesembryanthemum crystallinum. AB - The common ice plant, Mesembryanthemum crystallinum, shifts from C3 to crassulacean acid metabolism (CAM) photosynthesis in response to osmotic stress. The expression of a number of genes encoding enzymes involved in the CAM pathway increases as a result of increased transcription rates. To begin to investigate the mechanisms responsible for the transcriptional activation, we have characterized the 5' control region of a specific isoform of phosphoenolpyruvate carboxylase gene (Ppc1) that plays a key role in CAM. We have determined the nucleotide sequence of the 5' flanking region of this gene. Ppc1 contains a long 5'-leader sequence with the transcriptional start site located 332/333 nucleotides 5' of the translational initiation codon. Multiple DNA interactions with nuclear factors are detectable within the 5'-flanking region of Ppc1. We have used copper orthophenanthroline footprinting to demonstrate that one particularly abundant factor (designated PCAT-1) binds the Ppc1 promoter at two distinct A/T-rich sites located -128 to -158 and -187 to -205 bp upstream of the transcriptional start site. These binding sites share a loose consensus motif having the sequence AARTAAC(T/A)A(G/T)TTTY. Gel retardation competition experiments with oligonucleotides containing these A/T-rich binding sites suggest that both sites bind the same factor, but with different affinities. Fractionation of crude nuclear extracts by heparin-agarose chromatography indicates that PCAT-1 is more prevalent in extracts prepared from salt-stressed leaf tissue. Additional binding activities that interact with the PCAT-1 binding sites have been detected that either increase or decrease in abundance or binding affinity in response to salt stress. PMID- 1421146 TI - Identification and characterization of a full-length cDNA encoding for an auxin induced 1-aminocyclopropane-1-carboxylate synthase from etiolated mung bean hypocotyl segments and expression of its mRNA in response to indole-3-acetic acid. AB - 1-Aminocyclopropane-1-carboxylate (ACC) synthase (EC 4.4.1.14) is the key regulatory enzyme in the ethylene biosynthetic pathway. The identification and characterization of a full-length cDNA (pAIM-1) 1941 bp in length for indole-3 acetic acid (IAA)-induced ACC synthase is described in this paper. The pAIM-1 clone has an 87 bp leader and a 402 bp trailing sequence. The open reading frame is 1452 bp long encoding for a 54.6 kDa polypeptide (484 amino acids) which has a calculated isoelectric point of 6.0. In vitro transcription and translation experiments support the calculated molecular weight and show that the enzyme does not undergo processing. Eleven of the twelve amino acid residues which are conserved in aminotransferases are found in pAIM-1. The sequence for pMAC-1 which is one of the 5 genes we have identified in mung bean is contained in pAIM-1. pAIM-1 shares between 52 to 65% homology with previously reported sequences for ACC synthase at the protein level. There is little detectable pAIM-1 message found in untreated mung bean tissues; however, expression is apparent within 30 min following the addition of 10 microM IAA reaching a peak after approximately 5 h with a slight decrease in message after 12 h. These changes in message correlate with changes in ACC levels found in these tissues following treatment with 10 microM IAA. PMID- 1421147 TI - Alfalfa root nodule phosphoenolpyruvate carboxylase: characterization of the cDNA and expression in effective and plant-controlled ineffective nodules. AB - Phosphoenolpyruvate carboxylase (PEPC) plays a key role in N2 fixation and ammonia assimilation in legume root nodules. The enzyme can comprise up to 2% of the soluble protein in root nodules. We report here the isolation and characterization of a cDNA encoding the nodule-enhanced form of PEPC. Initially, a 2945 bp partial-length cDNA was selected by screening an effective alfalfa nodule cDNA library with antibodies prepared against root nodule PEPC. The nucleotide sequence encoding the N-terminal region of the protein was obtained by primer-extension cDNA synthesis and PCR amplification. The complete amino acid sequence of alfalfa PEPC was deduced from these cDNA sequences and shown to bear striking similarity to other plant PEPCs. Southern blots of alfalfa genomic DNA indicate that nodule PEPC is a member of a small gene family. During the development of effective root nodules, nodule PEPC activity increases to a level that is 10- to 15-fold greater than that in root and leaf tissue. This increase appears to be the result of increases in amount of enzyme protein and PEPC mRNA. Ineffective nodules have substantially less PEPC mRNA, enzyme protein and activity than do effective nodules. Maximum expression of root nodule PEPC appears to be related to two signals. The first signal is associated with nodule initiation while the second signal is associated with nodule effectiveness. Regulation of root nodule PEPC activity may also involve post-translational processes affecting enzyme activity and/or degradation. PMID- 1421148 TI - A major barley allergen associated with baker's asthma disease is a glycosylated monomeric inhibitor of insect alpha-amylase: cDNA cloning and chromosomal location of the gene. AB - A 14.5 kDa barley endosperm protein that is a major allergen in baker's asthma disease, as previously shown by both in vitro (IgE binding) and in vivo tests, has been identified as a glycosylated monomeric member of the multigene family of inhibitors of alpha-amylase/trypsin from cereals. A cDNA encoding this allergen (renamed BMAI-1) has been isolated and characterized. The deduced sequence for the mature protein, which is 132 residues long, is identical in its N-terminal end to the 20 amino acid partial sequence previously determined from the purified allergen, and fully confirms that it is a member of the multigene family of cereal inhibitors. Southern-blot analysis of wheat/barley addition lines using the insert in the BMAI-1 cDNA clone as a probe, has led to the location of the allergen gene (Iam1) in barley chromosome 2, while another related member of this protein family, the barley dimeric alpha-amylase inhibitor BDAI-1 gene (Iad1) has been located in chromosome 6. Iam1 is the first member of this inhibitor family in cereals to be assigned to chromosome group 2, thus extending the dispersion of genes in the family to five out of the seven homology groups of chromosomes in wheat and barley (chromosomes 2, 3, 4, 6 and 7). PMID- 1421149 TI - Purification and characterization of seven chloroplast ribosomal proteins: evidence that organelle ribosomal protein genes are functional and that NH2 terminal processing occurs via multiple pathways in chloroplasts. AB - Putative genes for 21 ribosomal proteins (RPs) have been identified in the chloroplast DNA of four plants by nucleotide sequencing and homology comparison but few of the gene products have been characterized. Here we report the purification and N-terminal sequencing of seven proteins from the spinach chloroplast ribosome. The data show them to be the homologues of Escherichia coli RPs L20, L32, L33, L36, S12, S16 and S19, and thus support the view that their genes identified in the chloroplast DNA represent functional genes. The initiating methionine residue was not detected in the mature protein in most cases but it was present in S16, indicating that only the formyl group is removed in this case. This result and the previously reported finding of N-methyl alanine at the N-terminus of chloroplast L2 indicate the existence of multiple N-terminal processing pathways in the chloroplast. PMID- 1421150 TI - The cruciferin gene family in radish. AB - In order to analyse the cruciferin gene family in radish a cDNA library was screened either with heterologous rapeseed probes or by differential screening and sequencing. We could identify six partial cDNA clones belonging to two different groups of cruciferin genes which do not cross-hybridize, and probably three distinct subfamilies. One of these classes corresponds to the previously described cruciferin from rapeseed and Arabidopsis. A gene corresponding to the second group, as well as its border sequences, was isolated from a radish genomic library and analysed in more detail. The cruciferin gene (cruRS) contains three introns and encodes a 479 amino acid protein. The transcription initiation site was determined. The expression of the different group of genes was studied by northern blot analysis: genes of both classes are expressed simultaneously and roughly at the same level between 25 and 35 days after flowering. Cruciferin gene copy number was estimated by Southern blot analysis. There appear to be seven or eight genes in one class and three in the other, located at different loci. PMID- 1421152 TI - Isolation and characterization of a tobacco gene with homology to pectate lyase which is specifically expressed during microsporogenesis. AB - A genomic clone has been isolated which contains an open reading frame of 1191 bp interrupted by two small introns. The ORF has been sequenced and the transcriptional start determined. The predicted amino acid sequence shows homology to the deduced amino acid sequences of two pollen-specific pectate lyase genes identified in tomato. The genomic clone was isolated using a partial cDNA clone, TP10, which had been isolated from a Nicotiana tabacum pollen cDNA library by means of differential screening. TP10 has been fully sequenced and contains an open reading frame of 792 bp which shows 96% homology to the ORF in the genomic clone. The transcript corresponding to TP10 is maximally expressed late in pollen development, and has not been detected in vegetative tissues. PMID- 1421151 TI - Cloning and sequencing of the petBD operon from the cyanobacterium Synechococcus sp. PCC 7002. AB - The genes encoding the photosynthetic cytochrome b6 (petB) and subunit 4 (petD) have been cloned and sequenced from the unicellular, photoheterotrophic, transformable cyanobacterium Synechococcus sp. PCC 7002, formerly designated Agmenellum quadruplicatum. The gene arrangement was found to be similar to that reported in the cyanobacterium Nostoc PCC 7906. The DNA and derived protein sequences were compared to chloroplast and the other cyanobacterial sequences. By pulsed-field electrophoresis, the petBD operon and the petCA operon, encoding the Rieske iron-sulfur protein and cytochrome f, were found to be located on separate, unlinked, Not I-digested DNA fragments. The petBD operon was found on the third largest Not I fragment (NC-325) while the petCA operon was found on the second largest Not I fragment (NB-370). These results suggest the two operons are not in proximity. The 1.35 kb transcript was shown to be light-regulated. Transcripts from cells grown under constant illumination showed a decrease in petB transcript levels to undetectable levels within 2 h after the cells were placed in the dark. Upon reillumination, transcript levels rose to three-fold over that seen initially under constant illumination. PMID- 1421153 TI - A DNA library from an individual Beta patellaris chromosome conferring nematode resistance obtained by microdissection of meiotic metaphase chromosomes. AB - We have used a standard protocol established for human chromosomes to create a chromosome-specific plasmid library from a Beta patellaris chromosome conferring nematode resistance. A monosomic addition line was chosen carrying 18 sugar-beet (Beta vulgaris L.) and one wild-beet (B. patellaris) chromosome. The wild-beet chromosome can readily be identified as a univalent during metaphase I of meiosis. Highly synchronized meiotic material was used to excise the univalents from four pollen mother cells. The chromatin was lysed in a 1 nl collection drop, the DNA purified and restricted with Rsa I, ligated into a vector containing universal sequencing primers, and amplified by the polymerase chain reaction. The amplified DNA was inserted into a standard plasmid vector and cloned. Approximately 23,000 recombinant plasmids were obtained of which 15,800 could be utilized. Their insert sizes ranged from 80 to 700 bp with an average of 130 bp. 61 clones were tested in more detail by genomic Southern hybridization with sugar beet and wild-beet DNA. Of these 32 plasmids (52%) contained single-copy inserts, 11 (18%) were specific for wild-beet DNA indicating that the DNA cloned originates in the univalent chromosome. The application of this technique for establishing high-density RFLP maps for discrete regions of plant genomes is discussed. PMID- 1421154 TI - Differential accumulation of mRNAs encoding extracellular and intracellular PR proteins in tomato induced by virulent and avirulent races of Cladosporium fulvum. AB - Tomato leaves infected by the fungal pathogen Cladosporium fulvum contain several types of intracellular and extracellular pathogenesis-related (PR) proteins. Previously, we reported the purification and serological characterization of five extracellular PR proteins: P2, P4, P6, a chitinase and a beta-1,3-glucanase [22, 23]. Here we describe the purification of a basic intracellular 33 kDa beta-1,3 glucanase and the isolation and characterization of cDNA clones encoding the two extracellular P14 isomers P4 and P6, the extracellular acidic beta-1,3-glucanase and a basic 35 kDa beta-1,3-glucanase, different from the purified 33 kDa protein. Southern blot analysis demonstrated that tomato PR proteins are not encoded by large gene families, as is the case in tobacco. The number of genes corresponding to each protein was estimated to vary between one and three. A northern blot analysis indicated that the mRNAs for the extracellular PR proteins (P4, P6 and acidic beta-1,3-glucanase) accumulate to similar levels in compatible and incompatible tomato-C. fulvum interactions, although the maximum level of expression is reached much faster in the incompatible interaction. On the other hand, the mRNA for the basic 35 kDa beta-1,3-glucanase is induced rapidly to high levels in both interactions, but declines in time to background levels only in the incompatible interaction. The relevance of this difference in relation to plant defence is discussed. PMID- 1421155 TI - Regulation of the maize HRGP gene expression by ethylene and wounding. mRNA accumulation and qualitative expression analysis of the promoter by microprojectile bombardment. AB - The expression of the maize gene coding for a hydroxyproline-rich glycoprotein (HRGP) has been studied by measuring the mRNA accumulation after wounding or ethylene treatment. RNA blot and in situ hybridization techniques have been used. The temporal and tissue-specific expression has been observed: the cells related to the vascular system show the more intense HRGP mRNA accumulation. Transcriptional constructions of the maize HRGP promoter have been tested on different maize tissues by microbombarding. A 582 bp promoter is able to direct the expression of the gus gene on calli and young leaves. Constructions having shorter promoter sequences lose this ability. The 582 bp construction retains the general specificity of expression observed for the HRGP gene. PMID- 1421156 TI - Import and processing of the precursor of the delta subunit of tobacco chloroplast ATP synthase. AB - A cDNA clone encoding the complete precursor of the delta subunit of chloroplast ATP synthase has been isolated from a tobacco (Nicotiana tabacum) leaf cDNA library in lambda gt11. The 880 bp insert encodes a polypeptide of 248 amino acid residues, of which 61 residues constitute an N-terminal presequence and 187 residues make up the mature delta subunit. Transcription and translation of the cDNA in vitro produced a protein of 29 kDa which was imported by isolated pea chloroplasts and processed to the mature 20 kDa subunit. The delta subunit precursor was processed to the mature size by a processing peptidase present in pea stromal extracts. Hybridisation of the cDNA to Southern blots of tobacco genomic DNA suggests the presence of two genes in the haploid genome. PMID- 1421157 TI - Expression of desiccation-related proteins from the resurrection plant Craterostigma plantagineum in transgenic tobacco. AB - Three cDNAs encoding desiccation-induced proteins from the resurrection plant Craterostigma plantagineum were each ligated to a triplicated CaMV 35S promoter and a nopaline synthase 3'-flanking region in an Agrobacterium vector and introduced into tobacco. Transgenic plants expressed the encoded Craterostigma proteins at high levels. This did not lead to changes in the phenotype, in the growth habit or in basic photosynthetic parameters. In tobacco, one protein was targeted to the chloroplast stroma which is its normal location in Craterostigma. These desiccation-related proteins are not sufficient per se to increase drought tolerance as measured by ion-leakage tests. PMID- 1421158 TI - Characterization of a Brassica napus gene encoding a cruciferin subunit: estimation of sizes of cruciferin gene families. AB - A gene encoding a subunit of the 12S storage globulin, cruciferin, in Brassica napus (oilseed rape) has been isolated and characterized. The gene consists of about 2200 bp including three short intervening sequences. Primer extension analysis showed that the major transcription start site is located 30 bp 5' of the predicted ATG start codon. This gene belongs to one of three different major families encoding cruciferin subunits. By use of gene-family-specific probes and Southern blotting analysis the number of genes of the three different cruciferin subtypes in B. napus was estimated. PMID- 1421159 TI - Nucleotide sequence of a metallothionein gene of the thermophilic cyanobacterium Synechococcus vulcanus. PMID- 1421160 TI - Import of the precursor of the chloroplast Rieske iron-sulphur protein by pea chloroplasts. AB - cDNA clones encoding the precursor of the Rieske FeS protein of the chloroplast thylakoid membrane have been isolated from a pea leaf cDNA library in lambda gt 11, following screening with antibodies to purified pea chloroplast Rieske FeS protein. The longest cDNA insert of 880 bp encodes a polypeptide of 230 amino acid residues, of which 50 residues constitute an N-terminal cleavable presequence and 180 residues make up the mature protein. Transcription and translation of the cDNA in vitro produced a polypeptide of 26 kDa which was efficiently imported by isolated pea chloroplasts and processed to the mature 20 kDa protein. Southern hybridisation to pea genomic DNA indicated the presence of a single gene encoding the Rieske FeS protein in the haploid genome. PMID- 1421161 TI - Ras in signal transduction. AB - Ras protein is a GTP-binding protein, and acts as a signal transducer in fibroblast, lymphoid, myeloid, and neuronal cells. In all cases, tyrosine kinases, intrinsic to or associated with receptors, seem to play an important role for the activation of Ras in response to extracellular stimulations. A GDP/GTP exchange regulator and a GTPase stimulatory protein are thought to mediate signals from the kinases. The active Ras.GTP can cause different phenotypes, that is, proliferation, transformation, activation, or differentiation, depending on cell types, although it is not yet clear what is the primary target of the active Ras-GTP or how the various phenotypes are determined downstream of Ras protein. PMID- 1421162 TI - Prenoids and palmitate: lipids that control the biological activity of Ras proteins. AB - Ras proteins can be modified by two types of lipids--an isoprenoid and the fatty acid palmitate. These lipids help the otherwise cytoplasmic Ras protein to interact with the plasma membrane of a cell. The biological consequences of this association between Ras and membranes are dramatic, and can alter a cell's behavior from normal growth into malignancy. The scope and limits of our knowledge of the steps, structures and enzymes involved in this molecular transformation from soluble inactivity to membrane-bound potency are offered below. The prospects of regulating Ras function by controlling its intracellular location provides a tantalizing opportunity to translate research into a novel therapeutic reality. PMID- 1421163 TI - Three-dimensional structure of p21H-ras and its implications. AB - The three-dimensional structure of the H-ras oncogene product p21 has been determined in both its active, GTP-bound and its inactive, GDP-bound forms. This has supplied a wealth of information on the mode of binding of guanine nucleotides, on the mechanism of the GTPase reaction and on the conformational change of the protein which accompanies GTP hydrolysis. The structural analysis has also given clues to the interaction of p21 with the regulatory proteins GAP (GTPase Activating Protein) and nucleotide exchange factor. The three-dimensional structures of oncogenic mutants of p21 have also been determined and can nicely explain different biochemical and biological behaviour of these mutant proteins. PMID- 1421164 TI - GTPase activating proteins. AB - Since Ras proteins negotiate many signalling pathways leading to cell growth or differentiation, the regulation of Ras activity is vital to cellular health. Ras activity, which derives from a collaboration between Ras and GTP, is terminated by the GTPase activating protein (GAP)-catalyzed hydrolysis of the GTP. Hence, a simple regulatory scheme emerges: extracellular signals control Ras activity via membrane receptors and GAPs. However, the signalling scenario is probably not so simple. In looking for factors which interpret Ras activity, researchers have been led to the same factors which also regulate Ras activity, namely the GAPs. Therefore, it may be that Ras proteins are actually regulators of GAPs. PMID- 1421165 TI - Genetic analysis of ras homologs in yeasts. AB - Ras proteins with extensive structural homology to mammalian p21ras have been studied in the two yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. Comparative analysis of these two yeasts has revealed significant differences in the biochemical and physiological functions that are controlled by this subgroup of eukaryotic GTP-binding regulatory proteins. Despite such divergence of cellular functions, proteins and mechanisms involved in the regulation and modification of Ras proteins are highly conserved in yeasts and other eukaryotes. Genetic analysis of the function of yeast proteins that regulate or modify Ras proteins has provided important information about Ras proteins in general. PMID- 1421166 TI - Ras proteins in developmental pattern formation in Caenorhabditis elegans and Drosophila. AB - Recent studies of genetically isolated mutants in Caenorhabditis elegans and Drosophila have revealed ras functions in developmental pattern formation. The ras proteins act as genetic switches to determine cell fates between two alternative choices during C elegans vulval development (vulval versus hypodermal cells) and during Drosophila eye development (R7 versus cone cell). In both cases, ras proteins act downstream of a receptor tyrosine kinase in a signal transduction pathway that mediates cell-cell interactions. These genetic systems may allow the further elucidation of ras-mediated developmental regulatory pathways. PMID- 1421167 TI - ras activation in experimental carcinogenesis. AB - We review experimental models of carcinogenesis in which the role of ras activation has been most thoroughly studied: skin, thymus, mammary gland and liver. Qualitative changes (point mutations), as well as quantitative changes (over-expression, increased gene dosage) contribute to the transforming phenotype induced by ras genes. The activation of the three different ras family members is associated with particular tumor types, carcinogenic agents, and carcinogenic stages, suggesting the ras proteins may be involved in different biological functions. Depending on the system, ras activation has been shown to be an early and/or a late event in the multi-step process of carcinogenesis. These data underscore the possible relationship between ras activation and cell type specificity, proliferation, differentiation or cell-cell interaction. PMID- 1421168 TI - ras and human tumors. AB - Mutational activation of ras oncogenes is frequently encountered in human tumors. For unexplained reasons, K-ras mutations are predominantly found in pancreatic cancer, colorectal cancer and adeno-carcinoma of the lung, N-ras is predominantly found in a subset of acute leukemias and in myelodysplastic syndromes, while H ras mutations are rare. In most tumors, ras mutations are not clearly associated with specific clinical or biological features, but in lung cancer, childhood lymphoblastic leukemia and possibly in myelodysplastic syndromes ras mutations may predict a poor prognosis. Accumulating evidence suggests that exposure to chemical carcinogens is responsible for many ras mutations in humans. PMID- 1421169 TI - Regulation of DNA replication by the nuclear envelope. AB - Recent evidence suggests that the nuclear envelope is directly involved in regulating DNA replication. It does this in at least three ways. First, replication is dependent on assembly of an intact nuclear envelope capable of nuclear transport. Second, the nuclear membrane defines the nucleus as the fundamental unit of replication and determines the timing of initiation. Third, the nuclear membrane is essential for coupling DNA replication to the cell cycle. Thus, regulated DNA replication in eukaryotic cells depends on a structurally intact and functional nuclear envelope. PMID- 1421170 TI - Assembly and cell cycle dynamics of the nuclear lamina. AB - The nuclear lamina is a karyoskeletal structure composed of intermediate filament type proteins. It underlies the inner nuclear membrane and confers mechanical stability to the nuclear envelope. In addition, it interacts with chromatin and may thereby participate in determining the three-dimensional organization of the interphase nucleus. During mitosis, the nuclear lamina is transiently disassembled, most probably through hyperphosphorylation of lamin proteins by the protein kinase p34cdc2, a key regulator of the eukaryotic cell cycle. Mitotic disassembly of the lamina is necessary but not sufficient for nuclear envelope breakdown. Electron microscopic analyses have begun to provide insights into the principles that govern lamina assembly in vitro, and sequence motifs required for targeting newly synthesized lamins to the nuclear envelope have been identified. Of particular interest, lamins were shown to undergo a type of hydrophobic modification known as isoprenylation. Finally, recent studies addressing the nature of lamin-chromatin interactions may provide the basis for elucidating the role of lamins in organizing the distribution of interphase chromatin. PMID- 1421171 TI - An extended view of nuclear lamin structure, function, and dynamics. AB - Molecularly-based studies of nuclear lamins have progressed at a rapid rate in the last decade. However, we still have no answer to the most important question: what are the functions of lamins? In this review we describe recent experiments which challenge traditional views of lamin function and structure. These surprising results indicate that much lamin functionality remains to be discovered, and that more global approaches to lamin structure and function are especially appropriate at this time. PMID- 1421172 TI - Nuclear pore structure and function. AB - Nuclear pores are huge macromolecular assemblies, approximately 120 nm in diameter, that perforate the nuclear membrane and mediate nucleocytoplasmic transport. Nuclear pores are constructed from a cylindrical spoke-plug complex sandwiched between nucleoplasmic and cytoplasmic rings. The spoke-plug complex has pronounced 8-fold rotational symmetry, which is also present in the rings. Nucleocytoplasmic transport is an energy-requiring process that takes place through the centre of the pores and can accommodate particles up to about 25 nm diameter. Translocation is preceded by a separate binding step which does not require energy. Several nuclear pore proteins have been isolated and characterized. Many of these proteins contain O-linked N-acetyl glucosamine residues and may have similar modular domain structures. PMID- 1421173 TI - A high frequency of N-RAS oncogene mutations in multiple myeloma. AB - Mutation of the RAS oncogene was studied in ten patients with multiple myeloma, and the DNA from nude mouse tumors formed by cells obtained from tumorigenecity assays (in vivo selection assays) in these patients was analyzed by PCR and oligonucleotide hybridization. Mutations of the N-RAS oncogene were identified in two of three patients investigated by in vivo selection assay and in five of ten patients investigated by PCR analysis of DNA from myeloma cells. In the two former patients, mutation of the N-RAS oncogene was observed at the 61st codon. Of the five N-RAS mutant-positive patients investigated by the PCR analysis, one had a mutation at codon 12, two had mutations at codon 13, and two had mutations at codon 61. None of the patients had mutations of the K-RAS oncogene. These results suggest that the frequency of RAS gene mutation in multiple myeloma is higher than in other lymphoid malignancies such as acute lymphocytic leukemia, chronic lymphocytic leukemia, and malignant lymphoma. As the mutation was observed only at the N-RAS oncogene level, it is speculated that N-RAS oncogene activation might play an important role in the progression of multiple myeloma. PMID- 1421174 TI - Gene analyses of abnormal fibrinogens with a mutation in the gamma chain. AB - In four abnormal fibrinogens with a point mutation in the gamma chain, all characterized by impaired fibrin polymerization, we identified single base exchanges in the respective mutant gamma chain genes by polymerase chain reaction followed by DNA sequence analysis. These base exchanges accounted for the amino acid substitutions previously reported from our laboratory. They were exchanges of C to T (CGC for gamma Arg-275 to TGC for Cys) in fibrinogen Osaka II, T to G (AAT for gamma Asn-308 to AAG for Lys) in fibrinogen Kyoto I, T to C (ATG for gamma Met-310 to ACG for Thr) in fibrinogen Asahi, and G to T (GAT for gamma Asp 330 to TAT for Tyr) in fibrinogen Kyoto III. These base exchanges were found to reside in exon VIII of the gamma chain gene. Since many abnormal molecules are associated with polymerization defects, unless associated with the impaired release of fibrinopeptides A and/or B, exon VIII of the gamma chain gene may deserve careful study to define the structural alterations. PMID- 1421175 TI - Altered expression of protein kinase C in adult T-cell leukemia cells. AB - Protein kinase C (PKC) has been shown to be involved in the mitogenic response and in oncogenic cell transformation in many experimental models. We analyzed the expression of PKC in both highly purified leukemic T cells freshly isolated from adult T-cell leukemia (ATL) patients and control T lymphocytes obtained from healthy volunteers. PKC activity was decreased in the ATL cells as compared with the control T cells. Cytosolic PKC activity in the ATL cells was remarkably decreased, whereas particulate membrane PKC activity was similar to the control level. The percentage of PKC activity in the particulate fraction was 34% in the ATL cells and 19% in the control cells. Regarding the altered subcellular localization of PKC activity, phorbol ester-induced translocation of cytosolic PKC was inhibited in some ATL cases. Similarly to the decrease in PKC activity, there was a decrease in the expression of the major PKC isozymes II(beta) and III(alpha) in ATL cells. These results suggest impaired regulation of PKC expression in ATL as well as in many experimental cancers. PMID- 1421176 TI - Hirudin and sulotroban improve coronary blood flow after reperfusion induced by the novel recombinant plasminogen activator BM 06.022 in a canine model of coronary artery thrombosis. AB - Thrombus formation in anesthetized, open-chest dogs was induced by electrical injury to the intimal surface of the left circumflex coronary artery. One-hour postocclusion, administration of vehicle to heparinized dogs (n = 12) did not induce reperfusion despite concomitant treatment with acetylsalicylic acid (ASA), sulotroban, or saline. Intravenous bolus injection of 140 kU/kg (= 0.24 mg/kg) of the unglycosylated t-PA variant BM 06.022 induced reperfusion in 4 out of 6 dogs, followed by flow deterioration. Pretreatment with i.v. ASA did not improve coronary blood flow (CBF). Conjunctive treatment with the thromboxane A2-receptor antagonist, sulotroban, (10 mg/kg i.v. bolus, followed by 10 mg/kg/h) or with recombinant hirudin, a specific thrombin inhibitor, (1 mg/kg/h) 30 min prior to i.v. injection of BM 06.022, prolonged (p < 0.01) the cumulative patency time (sum of time-intervals in which the coronary artery was patent) to 147.4 +/- 9.2 min in 4 out of 6 reperfused dogs and 129.9 +/- 12.3 min in 7 out of 8 dogs, respectively, compared to the saline plus BM 06.022 treatment (47.5 +/- 13.1 min) in 4 out of 6 dogs. The terminal CBF was higher (p < 0.01) after sulotroban plus BM 06.022 (7.0 +/- 1.7 ml/min) and hirudin plus BM 06.022 (6.3 +/- 1.5 ml/min) than after saline plus BM 06.022 (0.8 ml/min). These findings demonstrate that drugs with antithromboxane or antithrombin activity may improve CBF after reperfusion. PMID- 1421177 TI - Rapid prenatal diagnosis of Hb Bart's hydrops fetalis in southeast Asia area by polymerase chain reaction. AB - We used the polymerase chain reaction (PCR) to amplify the breakpoint area of alpha-thalassemia-1 of Southeast Asia type and several parts of the alpha-globin gene cluster to make a differential diagnosis between alpha-thalassemia-1 and Hb Bart's hydrops fetalis. The procedure involved three primers to detect the homozygote of alpha-thalassemia-1, then amplifies the other alpha-globin gene cluster with three other pairs of primers to double check the results. The PCR products were checked again by allele specific probes. Twenty-two cases were diagnosed prenatally, two were normal, 17 were alpha-thalassemia-1, and three Hb Bart's hydrops fetalis. All cases were confirmed either by Southern blot hybridization or follow-up by sonography or after delivery. No false positive or false negative results were obtained by our strigent procedure. We conclude it to be a rapid, accurate and economic method. PMID- 1421179 TI - Effects of cobalamin, cobalamin analogues and cobalamin binding proteins on P388D1 mouse leukemic cells in culture. AB - Cobalamin-deficient P388D1 mouse leukemic cells were created by propagation in a cyanocobalamin-free medium in which the original fetal bovine serum was replaced by bovine serum albumin. These cobalamin-deficient cells gradually ceased to multiply when the medium contained 5-methyltetrahydrofolate. The growth of cells that had been cultured with this coenzyme was recovered following the addition of cyanocobalamin (CNCbl), at concentrations above 37 pM. In contrast to the effect of CNCbl, cobinamide, and cobalamin analogues prepared from hydroxy cobalamin by reaction with ascorbic acid, did not have a growth-inducing effect on these cells, nor did these analogues inhibit CNCbl-dependent growth. Transcobalamin II cobalamin complex had a remarkably stimulating effect on cell growth. The growth inducing effect became apparent with a cobalamin concentration of only 0.37 pM. This was about 1/100th the level of free cobalamin required for cell growth. However, no growth-inducing effect was seen at an R protein-bound cobalamin concentration of 37 pM, indicating that once cobalamin has been bound to R protein, it loses its growth-promoting effect on these cells in culture. PMID- 1421178 TI - Circulating transferrin receptor in acute leukemias. AB - Serum transferrin receptor (s-TR) levels in acute leukemia patients were measured by a recently developed sandwich radioimmunoassay. The mean s-TR level for normal subjects (n = 205) was 246 +/- 79 (mean +/- 1 SD) ng/ml. The values for patients with untreated acute myelocytic leukemia (AML, n = 18) and untreated acute lymphocytic leukemia (ALL, n = 14) were 398 +/- 175 ng/ml and 479 +/- 176 ng/ml, respectively, both of which were significantly higher than those for the normal subjects (AML, p < 0.02; ALL, p < 0.05). When complete remission was achieved with initial remission induction therapy, s-TR decreased to 262 +/- 47 ng/ml (n = 22, 12 AML and 10 ALL), returning to normal levels. There was a good correlation between s-TR levels and the number of leukemic cells in peripheral blood (r = 0.743, n = 32, p < 0.01). In two patients with AML, serial changes of s-TR values and numbers of blast cells in the peripheral blood and bone marrow occurred in a parallel manner. If, therefore, this assay for s-TR can be made more sensitive, it may become useful for assessing acute leukemia activity and for monitoring the effects of therapy. PMID- 1421180 TI - Primary extramedullary plasmacytoma of the small intestine. AB - We report a case of primary extramedullary plasmacytoma (PEMP), IgA kappa type, with a long clinical history, in a 64-year-old Japanese woman. In this case, PEMP occurred primarily in the jejunum and then recurred in several organs, specifically the spleen and stomach, and in the subcutaneous tissue, over a period of about 16 years. However, examination of bone marrow aspirates on several occasions continued to show no plasmacytoma involvement. The patient is still living. Immunohistochemical examinations revealed monoclonal IgA kappa immunoglobulin in the cytoplasm of infiltrating plasma cells in all surgical specimens examined. Immunoelectrophoresis revealed serum M-component only when the patient had a splenic tumor. Soon after splenectomy, the serum M-component disappeared. PEMP of the small intestine is rare. PMID- 1421181 TI - Monitoring hemangioblastoma tumor burden using plasma erythropoietin levels. AB - We report a 39-year-old female patient with a hepatic hemangioblastoma, polycythemia and elevated plasma erythropoietin (Epo) levels. Following orthotopic liver transplantation (OLTx), her plasma Epo levels and hematocrit normalized but began to rise several months later. This rise correlated with the appearance of multiple lung metastases. The tumor was implicated as the source of excess Epo production using Northern analysis of a resected metastatic lung nodule. Based on our results, the measurement of plasma Epo levels in patients with Epo secreting tumors could be of general utility in assessing tumor burden. PMID- 1421182 TI - [Transthoracic lung biopsy. A useful but unused method?]. PMID- 1421183 TI - [The determination of myocardial mass by cardiac magnetic resonance tomography. The effect of section alignment and section distance]. AB - The effect of section alignment and distance in volumetric determination of myocardial mass by means of cardiac magnetic resonance imaging (MRI) was studied in 19 isolated pig hearts. Double angulated views taken through the short axis of the heart with a slice thickness of 10 mm and slices at a distance of 0 mm, 1 mm, 3 mm and 5 mm produced accurate left ventricular measurements with cardiac MRI. Measurements in the long axis of the heart resulted in a marked underestimation of myocardial mass; depending on slice intervals, there was an error between 13% and 20%. In vivo measurements in 35 subjects confirmed the effect of section alignment. Measurements in the long axis of the heart produced results of 139.9 +/- 31.7 g, significantly less than measurements in the short axis of the heart of 157.8 +/- 32.3 g. PMID- 1421184 TI - [Measurement error estimation in MR tomographic volumetry of the left ventricle with the multisection technic]. AB - A multi-slice technique for MRT measurements of the left ventricular volume is much faster than the use of single-slice methods and is therefore better tolerated, leaving time for additional measurements. The end-diastolic left ventricular volume can be reliably measured by this method (123.3 +/- 13.5 ml vs. 124.1 +/- ml). The end-systolic volume is consistently overestimated by 23.7 +/- 18.3% compared with the reference value obtained by single slice measurements (47.9 +/- 8.9 ml vs 39.1 +/- 7.9 ml). Correspondingly, stroke volume and ejection fraction is underestimated on average by 10.6 +/- 9.7% and 10.6 +/- 7.6% respectively). PMID- 1421186 TI - [In-vivo 31P-NMR-spectroscopy in patients with dilated cardiomyopathy]. AB - In vivo 31P-NMR spectra of heart muscle were obtained in 7 patients with dilating cardiomyopathies and in 10 normal subjects, using an ISIS technique with a 1.5 Tesla body scanner (Philips Gyroscan S15) and the results of the two groups were compared. These results were easily reproduced. In patients with cardiomyopathy there was a significant (p < 0.05) reduction of the PCr/ATP ratio as an expression of abnormal energy metabolism. Two patients with mild clinical symptoms and only slightly reduced functional measurements showed no significant changes in the 31P-NMR spectrum. The patients with the largest reduction of the PCr/ATP index also showed the most marked changes in functional measurements. The PCr/ATP ratio (as also suggested by animal experiments) appears to be a suitable non-invasive indicator for the diagnosis and staging of myocardial changes in dilating cardiomyopathies. PMID- 1421185 TI - [The direct measurement of the spin-grid-relaxation times of phosphorus metabolites in the human myocardium]. AB - The T1 relaxation times of the phosphorus metabolites in human heart muscle measurable by 31P-MR spectra were determined in 12 individuals using a 1.5 Tesla system. Several spectra were recorded consecutively with a pulse repetition time of 1.6 s to 24 s. The T1 times of creatine phosphate (CP), of gamma-, alpha-, beta-adenosintriphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG) together with anorganic phosphate) and phosphodiester (PDE) showed mean measurements of 6.1 +/- 0.5, 5.4 +/- 0.5, 5.0 +/- 0.5, 5.8 +/- 1.0, 7.6 +/- 1.0, and 5.0 +/- 1.0 s (M +/- SE). The accuracy of the ISIS technique was tested with a special phantom. T1 times were also measured in standard solutions (20 mM CP, 10 mM ATP); CP was 8.7 +/- 0.2 s and gamma-ATP was 9.9 +/- 0.7 s. Corrections for partially saturated 31P-MR spectra--at least for CP/ATP ratios--are relatively small. PMID- 1421187 TI - [MR tomographic volumetry of the subarachnoid space in HIV-associated brain atrophy]. AB - The CSF volume of 45 patients with HIV infection was measured at various clinical stages and the results compared with 24 normals. 60% of all patients showed increased CSF spaces as an indication of cerebral atrophy. Serial measurements were particularly valuable during the early stages of atrophy since there is marked variation in the normal CSF volume. Conventional measurements, with the exception of the width of the third ventricle, were much less sensitive than these quantitative measurements. Classification of HIV infection according to the clinical stage was useful since CSF volume and volume increase correlated with the stage of HIV infection. PMID- 1421188 TI - [Magnetic resonance tomography in the follow-up after the embolization of arteriovenous malformations of the central nervous system]. AB - Interventional embolisation is an accepted treatment for intracranial or spinal arteriovenous malformations. Since multiple embolizations are often required, noninvasive repeatable follow-up studies are desirable. The aim of this study is to demonstrate the usefulness of T2-weighted images, MR angiography, and gadolinium-DTPA first-pass studies for post-embolisation follow-up studies. Five patients with arteriovenous malformations, four cerebral and one spinal, were studied prospectively before and repeatedly after single or multiple embolizations. A total of 26 MRI studies (1.5 T Magnetom, Siemens AG) were performed. The combination of T2-weighted images, MR angiography, and gadolinium DTPA first-pass studies nicely demonstrated the arteriovenous malformations and the effect of embolisation which ranged from negligible to almost complete. While contrast-enhanced T1-weighted images and contrast-enhanced MR-angiography seemed to be of little more value than unenhanced studies, gadolinium-DTPA first-pass studies appeared to be more sensitive than T2-weighted images or MR-angiography because of their high intrinsic sensitivity to regional blood flow and volume. In the spine, T2-weighted images and MR-angiography were too insensitive to detect arteriovenous malformations, whereas gadolinium-DTPA first-pass studies sensitively detected the malformation and the changes after embolizations. PMID- 1421189 TI - [A prospective study to determine the recanalization time with a guide wire/recanalization catheter system in arterial occlusions]. AB - The success rate and time taken for recanalization was determined in a prospective study of 82 consecutive unselected patients (53 men, 29 women; mean age 65.7 +/- 13, from 28 to 88 years). There were 106 complete occlusions of infrarenal arteries and a hydrophilic guide wire with a special 5-F recanalization catheter was used. Mean occlusion length was 12.97 +/- 10 cm (from 1 cm-45 cm). 79.3% of occlusions were in the femoro-popliteal territory, 6.6% were iliac and 14.1% tibial. 101 of the 106 occlusions were recanalized (95.3%). Mean recanalization time was 120.8 +/- 228.1 s (from 1 s-1440 s), mean recanalization velocity was 0.11 cm/s. The majority of obstructions could be recanalized in less than one minute. The five occlusions which could not be recanalized were distal lesions in the superficial femoral artery and which were longer than 10 cm; two were calcified. There were no complications resulting from the recanalization apart from three perforations which were clinically not apparent. Consequent angioplasty proved successful in 78.1% of these patients. PMID- 1421190 TI - [Long-term observation after percutaneous transluminal angioplasty in the pelvic and leg areas]. AB - In this study 163 patients had long term follow ups after PTA; the value of a test which had previously hardly been used, the "Cox proportional hazards model", for prognostic purposes is stressed. In this test account is taken of the severity of the stenosis before PTA, the extent of re-stenosis following PTA and the distance of the occlusion from the aorta and these are related to the likelihood of success. The use of the Cox proportional hazards model with an accurate description of the clinical material and the use of the Kaplan-Meier method is recommended in order to obtain comparable figures for the results obtained in various centres. In this study patency after six months was 77%, after a year 67%, after three years 46% and after five years 37%. PMID- 1421191 TI - [The catheter embolization of acute hematuria after percutaneous nephrostomy and nephrolitholapaxy]. AB - Angiography was performed on 6 patients with acute haematuria following percutaneous nephrostomy and nephrolitholapaxy; in 3, vessel damage with leak of contrast into the nephrostomy canal or renal parenchyma was demonstrated and in 3 there were one or more pseudoaneurysms with or without arteriovenous fistula. All patients were successfully treated by catheter embolisation. Various catheter techniques (monaxial, coaxial) and embolic materials (Spongostan, Ivalon, coils) were used. The use of a Tracker-18 catheter with micro coils is the method of choice and permits superselective embolisation of bleeding from small peripheral branches with maximal preservation of the renal parenchyma. PMID- 1421192 TI - [The imaging diagnosis of acute renal transplant obstruction with special reference to antegrade pyelography]. AB - 30 patients with an acute build-up of renal transplant were examined comparatively via antegrade pyelography (AP), computed tomography (CT) and sonography (SONO). In the proof of obstructions and compressions of the ureter of renal transplant, antegrade pyelography was superior to sonography and computed tomography. Perirenal collections of fluids were recognised correctly via sonography by 73% (11/15) and computed tomography by 87% (13/15). The computer tomogram is superior in the differentiation of perirenal collection of fluids. In establishing proof of the cause of an acute build-up of renal transplant it was evident that computed tomography with a sensitivity of 64% and a specificity of 94% was slightly superior. PMID- 1421193 TI - [Renal osteodystrophy: the spectrum of the x-ray symptoms in modern forms of kidney transplantation and long-term dialysis therapy]. AB - Plain film radiography and microradioscopy represent standard imaging for diagnosis and grading of renal osteodystrophy. The aim of this retrospective study was to evaluate the effects of modern therapeutic regimens on skeletal abnormalities as diagnosed radiographically. 198 patients were investigated. X ray findings of 38 patients from 1981-1983 (16-66 years, 40.1 +/- 13.4; 23 male, 15 female) were compared with those of 160 patients from 1991 (20-71 years, 48.4 +/- 12.5; 98 male, 62 female). We found significant differences in respect of the spectrum and the degree of skeletal abnormalities. The prevalence of phalangeal resorptions lowered from 87 to 50%, the prevalence of soft tissue calcification from 68 to 57%. Therefore, renal osteodystrophy is not as extensive as it was ten years ago, but it still continues to be an unavoidable complication of renal insufficiency. PMID- 1421194 TI - [The imaging diagnosis of sclerosing peritonitis (SP) following continuous ambulatory peritoneal dialysis (CAPD)]. AB - Sclerosing peritonitis is a serious complication of CAPD characterised by thickened peritoneal membranes which lead to decreased ultrafiltration and intestinal obstruction. The roentgenographic signs of SP were analysed in 11 patients who underwent plain x-ray of the abdomen, follow-through examinations of the small bowel, ultrasonography and computed tomography. Results were correlated with the histological degree of SP. Besides the non-specific findings of intestinal obstruction, patients with histologically marked SP had loculated fluid collections, thickening of the bowel wall and/or peritoneum, peritoneal calcifications and thickened peritoneal membranes. Due to the fact that postoperative complications often occur in patients with SP, detection of the radiological signs should lead to cautious surgical interventions and changeover to haemodialysis. PMID- 1421195 TI - [The preoperative marking of nonpalpable breast lesions: the technic and results]. AB - 189 non-palpable breast lesions in 182 patients were localized using conventional mammographic apparatus, a wire grid compression plate and a cannula with a hooked mandrin. The technique of the examination for defining the lesion in three planes and fixation of the lesion with the wire is described. In 173 instances (91.5%), the lesion was found at the first biopsy and subsequent biopsies were necessary on only 24 occasions. One lesion (0.5%) was missed completely. 47 carcinomas were found (24.9%) and the incidence of malignancy increased from 14.3% to 33.3% during the series. The mean ratio defining the size of the biopsy and the size of the lesion was 3.3 and indicates good preservation of breast tissue. Radiographs of the specimen taken with compression showed 186 lesions (98.4%). The method, which is comfortable for the patient, provides satisfactory detection and localization of the lesions; results are similar to those of stereotactic methods but this method is quicker and much less expensive. PMID- 1421196 TI - [Pseudothrombosis of the vena cava superior and other flow artifacts in high resolution rapid computed tomography of the thorax]. PMID- 1421197 TI - [Sonography and computed tomography in intraperitoneally retained abdominal drapes]. PMID- 1421198 TI - [The nuclear magnetic tomographic imaging of a fistula between the right coronary artery and the left atrium]. PMID- 1421199 TI - [The absent cervical pedicle syndrome. A rare anomaly of the cervical spine]. PMID- 1421200 TI - [An advanced stage of a bilharziasis infection in CT diagnosis]. PMID- 1421201 TI - [Re: the article by G. Barzen et al.: The value of radioimmunoscintigraphy..., Forstchr. Rontgenstr. 156 (1992) 3-10]. PMID- 1421202 TI - Changes in the blood-brain transfer of L-phenylalanine elicited by arginine vasopressin. AB - Arginine vasopressin (AVP) coinjected into the carotid artery in physiological concentrations (0.1 nmol/l) with L-[3H]phenylalanine changed the kinetic parameters of blood-brain barrier (BBB) transport of this neutral amino acid. The half-saturation constant (Km) and the maximum velocity of transport (Vmax) were estimated in nine brain regions of male Wistar rats anaesthetized with ether. In the cerebral hemisphere Km decreased significantly from 0.107 to 0.061 mmol/l and Vmax from 37.6 to 27.4 mmol/min/g. Comparing the kinetic constants for the phenylalanine transfer of corresponding regions of control animals and those coinjected with the amino acid and AVP, 8 out of 9 (Km) and 7 out of 9 (Vmax) regions were found significantly lowered. The findings support the hypothesis that AVP binding to the endothelial cell layer of the brain capillaries induces alterations of the transfer of at least the large neutral amino acids (LNAAs) from blood to brain. The kinetic parameters estimated for L-phenylalanine favour the assumption that in vivo AVP induces a preferred transport of this amino acid across the BBB compared to L-leucine. PMID- 1421203 TI - Effect of mesulergine on prolactin secretion and dopamine D2 receptors-adaptive changes in diethylstilbestrol-induced hyperplasia of the rat anterior pituitary. AB - Mesulergine (N,N-dimethylsulphamide-N'-1,6-dimethyl-ergoline-8 alpha-yl) is an active semisynthetic ergot derivative with lower antiprolactin potency compared with bromocriptine or pergolide. Since no data are yet available on the effects of mesulergine on pituitary dopamine receptors, the present study has been designated to elucidate the influence of this drug on prolactin secretion in vivo and in vitro and 3H-spiperone binding by the anterior pituitary gland in female Wistar rats with experimentally induced hyperprolactinemia. Three weeks after bilateral ovariectomy and subcutaneous implantation of silastic tubes, containing 10 mg of diethylstilbestrol, a dramatic rise in serum prolactin levels was observed (1.67 +/- 0.23 vs. 80.82 +/- 3.80 ng/ml; P less than 0.001). Mesulergine attenuated the stimulatory effect of diethylstilbestrol on serum prolactin level in a time- and dose-dependent fashion. At concentration range between 10(-5) and 10(-7) M it also inhibited prolactin secretion from cultured rat pituitary cells to the medium during 180 min incubation in a dose-dependent manner. Scatchard analyses performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture, prepared from the pituitaries from rats treated for four weeks with diethylstilbestrol, showed that chronic mesulergine treatment (in dose of 3.0 mg/kg injected s.c. for 10 days) induced a significant decrease in the number of dopamine D2-binding sites (Bmax 28.00 +/- 4.20 vs. 42.80 +/- 4.76 fmol/10(6) cells; P less than 0.01) without any changes in D2-receptor affinity. Our results suggested that antiprolactin activity of mesulergine in vivo and in vitro is probably associated with agonistic effect of this drug on D2 dopamine receptors. PMID- 1421204 TI - Low concentrations of oxytocin suppress lordosis when infused into the lateral ventricle of female rats. AB - The first experiment was undertaken to compare the effects on lordosis of the infusion of oxytocin into the lateral versus the third ventricle. Female rats fitted with bilateral cannulae aimed at these ventricles were primed with 5 micrograms estradiol benzoate and 150 micrograms progesterone and received an infusion of 0.34 ng oxytocin into either the left lateral or the third ventricle. The infusion of 0.34 ng oxytocin into the left lateral ventricle inhibited lordosis behavior, while the same dose infused into the third ventricles of the same animals did not. Since a facilitation of lordosis in response to the infusion of oxytocin into the lateral ventricle has been reported in other studies, it seemed possible that the inhibition and facilitation could be produced by different doses of oxytocin. In the second experiment this hypothesis was tested in another set of female rats fitted with unilateral cannulae aimed at the left lateral ventricle, primed with 5 micrograms estradiol benzoate and 150 micrograms progesterone and infused with different doses of oxytocin. In these animals the inhibition occurred with 0.34 ng but not with 3.4 ng or 34 ng of oxytocin. No facilitation was observed at any of these doses. PMID- 1421205 TI - Effects of dexamethasone on TRH and TRH precursor peptide (Lys-Arg-Gln-His-Pro Gly-Arg-Arg) levels in various rat organs. AB - The effect of an acute dexamethasone administration on thyrotropin-releasing hormone (TRH) and TRH precursor peptide (Lys-Arg-Gln-His-Pro-Gly-Arg-Arg) (p-8) levels in various rat organs has been studied. Rats were injected i.p. with 25 micrograms of dexamethasone/100 g body weight (group A), 500 micrograms of dexamethasone/100 g body weight (group B) or saline (group C). The rats were serially decapitated after the injection. TRH and p-8 levels in the hypothalamus, cerebrum, cerebellum and brain stem, stomach and eye and plasma TRH and thyrotropin (TSH) levels were measured by individual radioimmunoassays. P-8 levels in the hypothalamus decreased significantly in both group A and B at 1-4 hours after the injection, and then returned to pretreated levels at 24 hours after the injection. TRH levels in the hypothalamus increased significantly in both group A and group B at 1-4 hours after dexamethasone injection. No changes in p-8 and TRH levels were observed in other organs. In group A, plasma TRH levels tended to decrease at 1-2 hours, then to increase at 3 hours. In group B, plasma TRH levels decreased 1-4 hours after the dexamethasone injection, then increased at 24 hours. The plasma TSH levels decreased significantly at 1-4 hours in group A and group B, returned to pretreatment levels at 24 hours in group A, and increased significantly in group B at 24 hours after dexamethasone injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421206 TI - The role of some circumventricular organs in hormone action and secretion. PMID- 1421207 TI - Single point estimation of glucocorticoid receptors in lymphocytes of normal subjects and of children under long term glucocorticoid treatment. AB - A single point assay of glucocorticoid receptors (GR) in human lymphocytes based on the measurement of specific dexamethasone binding has been developed and compared with a common multi-point Scatchard analysis. The assay conditions concentration of the ligand 20 nmol/l, incubation time 2 h and the cell count 2-6 mil. cells/tube in the assay volume 0.25 ml were found to be optimal. An attempt was also undertaken to use a cell harvester for the separation of cells from unbound ligand. Though specifically bound dexamethasone measured by whole-cell assay and that using cell harvester correlated well, almost by one order lower values obtained with the latter method render it non-applicable for receptor quantitation. The results from 9 healthy volunteers (average GR concentration 7131 +/- 1256 sites/cell) correlated excellently with those obtained by the Scatchard analysis. The single point assay has been also applied for determination of GH in 10 children treated with large doses of prednisone. The average values from healthy volunteers did not differ significantly from those found in these children, though much broader range was found in patients. PMID- 1421208 TI - Androgen hydroxysteroid dehydrogenases under the influence of pyridoxine derivatives. AB - The metabolism of testosterone in the rat ventral prostate, anterior pituitary, basal hypothalamus and amygdala was studied in vitro under the influence of vitamin B6 compounds. The influence of these compounds on the activity of 5 alpha reductase (5 alpha-R), 3 alpha- and 17 beta-hydroxysteroid dehydrogenase (3 alpha HSD, 17 beta-HSD) was determined for all the examined tissues. Pyridoxine hydrochloride significantly increased the activity of 5 alpha-R, 3 alpha- and 17 beta-HSD, but pyridoxal hydrochloride had an inhibitory influence on 5 alpha-R and showed no effect on 3 alpha-HSD activity at the prostate level. Male rat anterior pituitary, basal hypothalamus or amygdala incubated with pyridoxal phosphate and pyridoxal hydrochloride showed modified enzymatic activities. Pyridoxal hydrochloride showed an inhibitory effect on 5 alpha-R in the rat pituitary and basal hypothalamus as well as in the rat prostate. PMID- 1421210 TI - [Changes in impulse activity of neurons of the CA3 area of the hippocampus under the effects of neuromodulator neurotropin]. AB - Neurotropin (Nippon Zoki Co, Ltd) effects on firing patterns of the CA 3 hippocampus neurons in rabbits under a 24-h food deprivation was studied. Neuronal firing was recorded in a state of hunger (40 neurons) and under neurotropin (27 neurons) injected through a catheter implanted into the lateral brain ventricles. Initially, in 20% of neurons histograms had a bimodal interspike interval distribution: 1.5-25 ms and 100-400 ms. Neurotropin (50 microliters) increased the baseline spike rate regularity of hippocampus neurons. Histograms had a monomodal interspike interval distribution. Neurotropin (70 microliters) inhibited firing patterns and histograms, had trimodal interspike interval distribution: 1.5-5 ms; 250-400 ms and 1000 ms. Thus, these data suggested the involvement of neuro-immuno-modulator mechanisms in organization of firing patterns in rabbits. PMID- 1421209 TI - Inhibition of human serum oxytocinase (cystine aminopeptidase, E. C. 3.4.11.3) by GnRH peptides. AB - The hydrolysis of H-Cys(Bzl)-NH-Meq by human serum oxytocinase (E.C. 3.4.11.3) was inhibited non-competitively by various pyroglutamyl peptides. The most effective were the chicken GnRH II (Ki = 6 x 10(-6) mol l-1) and salmon GnRH (Ki = 12 x 10(-6) mol l-1), while the inhibitory potency of human GnRH was substantially lower (Ki = 60.0 x 10(-6) mol l-1). Variations in inhibitory potency of individual peptides reflected mostly the differences in N-terminal and C-terminal parts of the molecules. PMID- 1421211 TI - [Diurnal dynamics of red blood indicators after carotid glomectomy in rats]. AB - After bilateral carotid glomectomy the rat resistance to acute hypoxia reduces and phenomena of anemia arise. There appear correlations between resistance to hypoxia and red cell count, hemoglobin and hematocrit. The diurnal fluctuation of rat resistance to acute hypoxia after the glomectomy does not change while hemodynamics undergo marked changes. PMID- 1421212 TI - [Features of changes in bioelectric reactions of the cerebral cortex in rats with deafferentation pain syndrome]. AB - In rats with pain syndrome after sciatic nerve section the authors studied spontaneous and evoked bioelectric activity in sensomotor cerebral cortex of both hemispheres. Electrocorticogram showed the presence of hyper-synchronic discharges and paroxysmal peak-wave (700-800 mV) activity in contralateral hemisphere. While stimulating the injured limb the threshold of evoked potentials (EP) was observed to decrease, its amplitude to increase and focus maximum EP activity to extend. PMID- 1421213 TI - [Effects of neurotropin on seizure activity in picrotoxin kindling]. AB - It is shown that both intracerebral and intraperitoneal neurotropin administration resulted in a decrease of seizure susceptibility of preliminary picrotoxin--kindled rats. On the other hand, neurotropin did not change the course of kindling development. Under conditions of acute picrotoxin--induced seizures it was observed that preliminary cycloheximide (protein-synthesis blocker) administration abolished anticonvulsant properties of neurotropin. It is concluded that anticonvulsant effects of neurotropin are realized via modulation of endogenous peptides synthesis and, in particular, cerulein. PMID- 1421214 TI - [Relations between disorders of the intestinal-hepatic basin hemodynamics and absorption function in hemorrhage]. AB - Chronic dog experiments showed that blood loss of 30 ml/kg or an intravenous injection of 1 microgram/kg norepinephrine did not markedly change small intestinal absorption. Blood supply to the liver was maintained at the expense of restricted portal circulation. Adaptation in blood loss seems to support arterial blood supply to the liver and absorbing epithelium of the small intestine to warrant their resistance to circulatory hypoxia and to promote their functional activity. PMID- 1421215 TI - [Changes in EEG and higher nervous activity of rats during cerebral anti-ischemic protection by acelysin]. AB - The water-soluble aspirin (acelysin) has been used as an anti-ischaemic protector when injected in the dose of 150 mg/kg 30 min before ischaemia. The EEG has been registered during the whole period of experiment and the total EEG power index has been calculated. The higher nervous activity has been evaluated during analysis of rat's abilities for elaboration of conditional reflex of an active escape reaction in Y-labyrinth. The results have demonstrated the complete rehabilitation and restoration of brain functional activity 8 days after endurance of brain ischaemia under protection of acelisin. PMID- 1421216 TI - [Use-dependent inhibition of C-axon multimodal units of cat skin by lidocaine and N-propyl-ajmaline]. AB - Subcutaneous application of local anesthetic drug lidocaine and cardiac antiarrhythmic n-propyl-ajmaline produced the reversible use-dependent inhibition of feline polymodal mechano-heat C-fiber cutaneous sensory units (CMH-units) excited by moderate noxious mechanical stimulus. The discharge rate as well as the number of evoked spikes of polymodal sensory units treated with the drugs decreased below the values observed under noxious chemical excitation of CMH units. The repeated mechano-stimulation with 5 to 30 sec interval between stimuli produced complete though a reversible block of the treated units. Quaternary amine n-propyl-ajmaline induced use-dependent inhibition of CMH-units in lower concentrations than tertiary amine lidocaine. The use-dependent inhibition of CMH units is discussed in connection with nociception and local analgesia. PMID- 1421217 TI - [Parameters of systemic hemodynamics in conscious rats with acute streptozotocin diabetes]. AB - The effect of acute streptozotocin-induced diabetes mellitus on the systemic hemodynamic parameters was studied in conscious rats by thermodilution technique. Male Wistar rats were made diabetic with a single intravenous injection of streptozotocin (STZ, 50 mg/kg). The most important finding of this work was the elucidation of the systemic vasodilation and increased cardiac index one day after STZ injection. Such alteration in hemodynamic parameters could result in the increased blood flow and capillary hypertension in some vascular beds and, therefore, be considered as a pathogenic factor in the development of diabetic microangiopathy. PMID- 1421219 TI - [Participation of tyrosine residues of myoglobin in the disproportionateness reaction of heme iron (II) and (IV)]. AB - By means of the comparison of the constant oxidation reactions of both the myoglobin modified by N-acetylimidazole and the intact myoglobin in the presence of H2O2 or ferrylmyoglobin we characterized the role of the tyrosine residues (Tyr) of myoglobin in the synproportionation reaction between heme iron (II) of one molecule and heme iron (IV)--of another. It was demonstrated that Tyr derivatization resulted in the decrease of the velocity of redox interaction between deoxymyoglobin (II) and ferrylmyoglobin (IV) and led to the decrease of the efficiency of oxymyoglobin deoxygenation. The effects were shown to be independent on Tyr quantity in myoglobin molecule and to have the same character for both the sperm-whale myoglobin and the horse myoglobin. PMID- 1421218 TI - [Effects of ubiquinone-9 on lipids of nuclei and chromatin of the rat liver under continuous irradiation]. AB - The influence of continuous gamma irradiation on the lipids of nuclei and chromatin of rat liver at a dose-rate of 0,129 Gy/day for 155 days (a total dose of 20 Gy) and by feeding of ubiquinone-9 has been studied. The amount of phosphatidylcholine with phosphatidylserine and phosphatidyl-ethanolamine in liver nuclei of irradiated rats was found to increase. Ubiquinone-9 had a normalizing effect. A decrease of cardiolipin was observed in the liver chromatin of irradiated rats. The amount of free fatty acids had a tendency to decrease in homogenate, nuclei and liver chromatin of irradiated rats. Ubiquinone was found to increase the amount of free fatty acids up to the control level. The amount of cholesterol in nuclei was increased after irradiation and that in chromatin tended to rise. Ubiquinone-9 significantly decreased the amount of cholesterol in nuclei and chromatin of irradiated rats. PMID- 1421220 TI - [Mechanisms of opioid peptide participation in the regulation of carbohydrate metabolism]. PMID- 1421221 TI - [Periodicity of changes in the concentration of cholesterol and blood serum proteins in dynamics of hypercholesterolemia]. AB - During 30-week hypercholesterolemia in rabbits and guinea pigs the differences in cholesterol dynamics manifested themselves in quantitative variations of blood serum proteins. Five weeks after the beginning of the experiment a sharp increase of cholesterol level corresponded to the equally sharp decrease of the quantity of blood serum total and cation proteins. The variation of protein and cholesterol concentrations in guinea pigs during 17 weeks is similar to the development of early stages of cholesterolemia (4 weeks) in rabbits. It can be supposed that there is a connection between metabolic systems involved in the transformation of blood serum cholesterol and blood serum. PMID- 1421222 TI - [Changes in the organization of the intermediate filament system of human fibroblasts in lysosomal storage diseases and their modeling]. AB - The organization of the system of the vimentin intermediate filaments (IFs) in human fibroblasts in lysosomal storage diseases (Fabry's disease, mannosidosis) and their modelling has been studied in vitro. It was shown that during accumulation of nonhydrolyzable compounds, hypertrophy of the lysosomal compartment is accompanied by formation of ring-shaped bundles IFs, surrounding apparently these increased organelles. The changed organization of IFs is characteristic of polarised pathological cells in monolayer, and after repassage it is retained only at the spreading state; on transition from the discoid to extended cellular form there occurred the centrifugal shift of ring-shaped structures of IFs to active cell border and gradual restoration of radial fibrillar state of IFs. It is suggested that on intralysosomal storage of unsplit compounds reorganization of the vimentin-type IFs in ring-shaped structure is necessary for optimal distribution and stabilization into the cytoplasm of large amounts of increased lysosomes with exo- and endogenous contents. In condition of free spreading (i. e. with diminished cell density) the restoration of normal fibrillar IF organization may be due to the loss of considerable number of hypertrophied lysosomes; the involvement of lysosomal membrane in formation of active cellular border is not to be ruled out. PMID- 1421223 TI - [A comparison of 3 methods of lipoprotein (a) isolation from human plasma]. AB - Three methods for purification of lipoprotein (a) [Lp(a)] from human plasma were compared. Method I: two-stage ultracentrifugation with subsequent gel-filtration of Lp(a) containing fractions (1.063-1.090 g/ml) on Sepharose CL-4B. Method II: ultracentrifugation followed by affinity chromatography of plasma fraction (1.063 g/ml) on anti-apoB sorbent. Method III: affinity chromatography of the whole plasma on anti-apo(a) sorbent. The Lp(a) yield of these methods is 35, 54 and 41%, respectively. The method III is preferable of these three because it permitted high purification of a large amount of Lp(a) by single-step chromatography. PMID- 1421224 TI - [Increase of seizure threshold and resistance to stress in rats after immunization against fragment of diazepam-binding inhibitor]. AB - White rats were immunized against fragment of diazepam-binding inhibitor octadecaneuropeptide (ODN) with conjugate ODN bovine serum albumin. This rats have reduced reactions of fear and anxiety in stress model of "open field" and in conflict Vogel test; their pain sensitivity ("tail flick" test) was lowered. The number and intensity of generalized seizure reactions after injection of pentylenetetrazole were decreased. The results show that active immunization to endogenous ODN has stress--protective and anti-seizure effects. PMID- 1421226 TI - [Toxic effects of heavy metal salts on intact and irradiated cultured mammalian cells]. AB - The toxicity of solutions of K2Cr2O7 and NiSO4.8H2O for cultivated Chinese hamster fibroblasts and murine lymphoma Sp-2 cells was determined using three criteria of damage: cell death (dyeing with trypan blue), inhibition of cell proliferation and their colony-forming activity. It was shown that both salts have equal toxicity in (10(-3)-10(-2)) M interval for both culture investigated relative to inhibition of cell proliferation. The threshold of toxicity of K2Cr2O7 relative to reproductive cell death (10(-4) M is smaller than to the inhibition of cell proliferation. The nontoxic concentration of K2Cr2O7 enhanced the radiation-induced reproductive death of fibroblast culture at doses 2 and 4 Gy. PMID- 1421225 TI - [Elimination of the atherogenic effect of beta blocker propranolol by papaverine]. AB - Recently, the ability of beta-blockers to stimulate proliferative activity and induce lipid accumulation in cultured human aortic intimal cells has been demonstrated. Moreover, the addition of calcium antagonists completely blocked the increase in proliferative activity and abolished cholesterol accumulation caused by propranolol. In this study blood serum of rabbits treated with 20 mg of propranolol induced 2-fold cholesterol accumulation in mouse peritoneal macrophages. Papaverin did not influence this effect. In case of simultaneous administration of propranolol and papaverin rabbit serum did not exhibit the ability to accumulate intracellular lipids. Propranolol substantially stimulated the formation of myointimal thickening and neutral lipid accumulation in denuded rabbit aorta. Papaverin completely blocked the propranolol-produced atherogenic changes. The data suggest that in vitro and in vivo atherogenic effects of beta blockers may be prevented by papaverin. PMID- 1421227 TI - [Disorders of bone marrow hematopoiesis long time after the action of cytostatic preparations]. AB - We studied the condition of CBA mice bone marrow hemopoiesis and functional activity of adherent cells 6 months after a single treatment with vinblastine (VB), doxorubicin (DR) and cyclophosphamide (CP) in LD10 dose (6, 22 and 250 mg/kg, respectively). There was a long-term disorganization of bone marrow cell composition. The damage may be attributed to exhaustion of the pools of stem cells and changes in function of the cells formed by hemopoiesis induction microenvironment. PMID- 1421228 TI - [Antipyrine metabolism and rat liver ultrastructure in single and combined action of trichlorodiphenyl and dioctyl phthalate]. AB - As shown by animal experiments, low-dose trichlorodophenyl and dioctyl phthalate induce microsomal cytochrome P-450-dependent enzymes and ultrastructural changes in hepatocytes. This evidences hepatotoxicity of the compounds. PMID- 1421229 TI - [Febrifugal activity of acupuncture and its strengthening by the effects of anaprilin]. AB - The power and duration of antipyretic actions of acupuncture under single or repeated stimulation of Shaoshang (Lu-11) and Shangyang (LI-1) acupoints were studied in rabbits. Under conditions of preliminary i. v. injection of propranolol (1-2 mg/kg), strengthening of acupuncture antipyretic activity was revealed. This effect suggests participation of norepinephrine system in mechanism of febrifugal action of acupuncture. PMID- 1421230 TI - [An experimental study of anti-amnestic activity of piracetam in orchidectomized rats]. AB - The decrease of learning ability by 50% as assessed by passive avoidance test and the increase 28% of microviscosity of synaptosomal membranes from brain cortex were observed in rats in a month after orchidectomy as compared with that of intact or sham--operated animals. The treatment of orchidectomized rats with piracetam either by single application or in the course of 10 days applications in the daily dose of 250 mg/kg intraperitoneally failed to improve learning ability of animals in passive avoidance test and to produce a normalizing effect on the structure of membrane lipid matrix. The testosterone content in blood of orchidectomized rats was 10 times lower as compared with control and was not affected by treatment with piracetam. PMID- 1421231 TI - [Effects of nitroglycerin on intracellular concentration of calcium in human blood platelets]. AB - It is shown that nitroglycerin has a calcium-blocking property in human platelets both at basal and ADP-induced calcium level, determined by fluorescence techniques (Fura-2). The study demonstrated a dose-dependent inhibitory effect of nitroglycerin on calcium rise, induced by ADP. 30-min preincubation with 60 microM nitroglycerin increased IC50 from 44 (without preincubation) to 320 microM, indicating the development of nitrate tolerance. It was suggested, that human platelet may be used as an experimental model of nitrate tolerance. PMID- 1421232 TI - [Characteristics of immunomodulating effect of histamine in inbred strain mice]. AB - The activity of 5'-nucleotidase of peritoneal exudate in subcutaneous injection of histamine in a dose of 1.0-100 microliters was studied in mice of different lines (CBA, C57, B1/6, Balb/c, NFS/n, NFR/n). There were interline differences in the influence of histamine on this metabolic index. PMID- 1421233 TI - [Sensitivity to mouse toxin and level of macrophage 5-nucleotidase activity]. AB - It is shown that immunomodulator of bacterial origin salmozan causes alternations of sensitivity to mouse toxin in mice CBA. A correlation exists between the sensitivity to mouse toxin and the level of 5-nucleotidase of peritoneal exudate macrophages. PMID- 1421234 TI - [Characteristics of lymphoid subpopulations of peripheral blood of patients with shigellosis]. AB - This work presents some investigation results of lymphoid subpopulation functional activity: Tg+1, Tg-1, Theophylline-resistant and Theophylline sensitive lymphocytes and O-1 isolated from the peripheral blood of patients with bacterial dysentery (BD) in local xenogenic GVHD. It has been established that Tg+1 and Tg-1 have stimulating effect on local xenogenic GVHD, but O-1 are inert though the quantity of Fcg+--receptor carrying lymphocytes among O-1 in BD and nonspecific ulcerative colitis is increased compared with donors. Theophylline resistant and Theophylline-sensitive lymphocytes demonstrated inhibiting effect on GVHD formation which was evident in the latter case. PMID- 1421235 TI - [Immunomorphological studies of the antigen associated with squamous cell cancer of the human cervix uteri]. AB - The existence of the antigen associated with human cervical squamous cell cancer in normal and pathologically changed cervical epithelium was studied. Immunocytochemical and immunohistochemical methods were used. It is shown that the levels of the antigen increase significantly as the severity of dysplastic changes in epithelial stratum grows and tumor invasive growth begins. The data obtained indicate that the above tumor-associated marker can be useful in the follow-up for prognosticating a course of cervical cancer and dysplasia. PMID- 1421236 TI - [Seasonal characteristics of the circadian rhythm of peripheral blood leukocyte content in Wistar rats]. AB - In Wistar rats, the seasonal variability of acrophase position, mesor value and circadian rhythm amplitudes of total leukocyte count, as well as of percentage and absolute lymphocyte count was revealed. The leukocyte count and absolute lymphocyte content were found highest in spring, while eosinophils--in autumn, neutrophils and monocytes--in winter. PMID- 1421237 TI - [Seasonal changes in amine-containing structures of the thymus during the 1st hour of antigen effects]. AB - Using luminescent-histochemical and microspectrofluorimetric techniques, the combination of early visual and quantitative changes of catecholamine and serotonin content in biogenic amine-containing thymus structures during the first hour contact of the body with the T-dependent antigen (sheep red blood cells) has been studied. The experiments were made on 60 male rats of Wistar-2 line, white laboratory rats in spring and autumn. The degree and direction of the changes were found to depend on the baseline neuromediator levels. PMID- 1421238 TI - [Cytoarchitectonics of pulpy cords in regional lymph nodes in rats with chronic carbophos poisoning]. PMID- 1421239 TI - [Effects of nerve growth factor on the development of the dendritic system of cholinergic neurons in dissociated culture of the rat septum]. AB - Neurons dissociated from septal area of fetal (E18-19) rat brain were grown 14 days in culture. Cholinergic neurons were identified by cytochemical demonstration of acetyl cholinesterase. It was shown that the nerve growth factor added to the culture medium (50 u/ml) has increased the size of cell body of AchE positive neurons, mean total length and arborization of dendrites and also the dendritic tree area. PMID- 1421241 TI - [Phosphate metabolism in the mineral matrix of intact bones and after single and multiple fractures]. AB - The level of mineral matrix phosphates in unbroken bones was investigated in rats with isolated and multiple fractures. It was found out that in bones lying close to the broken one the phosphates exchange shifts were similar to the changes happening in the region of the trauma. On the resorption stage the phosphates level in the nearby intact tissue decreases, during the bone callus formation it increases, and in the process of remodelling decreases again. The authors suggest that this zone should be identified under the term "trauma field". PMID- 1421240 TI - [Histological manifestations of the sparing effect of cooling in heat dissection of the cerebral cortex and liver]. AB - A new method of heat dissection of tissues combined with application of cooling was studied experimentally in white rats. Histologic changes of tissues of the cerebrum cortex and the liver wounds were investigated. It was found out that automatic selection of temperature regimen in combination of heat and cold ensured stable effect which was well balanced from the point of view of its depth and prevented overheating of tissues surrounding a wound channel. In comparison with cut wounds the above mentioned method allowed to gain better safety of cells. PMID- 1421242 TI - [Morphofunctional analysis of zinc-accumulating capacity of digestive system organs]. AB - The distribution of zinc and related changes have been studied in zinc--loaded chick pancreas, ileum and liver at the ultrastructural level by sulphide--silver method. White Leghorn chicks fed a high zinc diets (50, 500, 1000, 2000 and 4000 mgZn/kg diet) for 6 weeks, were killed at intervals; portions of their organs were fixed for light and electron microscopy; other samples were analyzed for zinc by AA spectrophotometry. A drastic increase of zinc level in chick pancreas fed 2000 mg Zn/kg diet (as ZnCl2) was associated with acinar cell degeneration. Apoptosis was the predominant form of acinar cell deletion. This study provides support for a previously proposed theory that cell injury stimulates passive zinc accumulation. PMID- 1421243 TI - [Structural-metabolic changes in the ventricular myocardium in massive experimental pulmonary embolism]. AB - A comparative study of hemodynamic and structural-metabolic changes in myocardium of right (RV) and left (LV) ventricles by compensative massive pulmonary embolism (MPE) and decompensated MPE was made in 29 mongrel dogs. By decompensated MPE the histoenzymological and ultrastructural methods reveal changes in RV which are not adequate to its high hemodynamic load: the catabolic enzymes activity decreases, the numeral density of mitochondrial profiles decreases too, the fraction of damaged mitochondria increases. By decompensated MPE the myocardial metabolism shifts from catabolic to biosynthetic processes, the activity of NADP.H-D and G-6 PDG increase in both ventricles. PMID- 1421244 TI - [Wound epithelialization in rats depending on the quantity and orientation of microautotransplants]. AB - Patches of autoskin (0.5 x 1.0 mm) were grafted on a full-thickness rat back skin wound (5.4 cm2). As a result of "island" epithelialization from microautotransplants (MATR), the skin defect underwent repair. It is shown that the advance of the wound re-epithelialization did not depend on MATR number and their orientation in relation to the wound surface. The use of MATR allows to restore the skin defect with the plastic coefficient 1:100. This reduces the deficiency of donor skin at extensive burns. PMID- 1421245 TI - [Evoked potentials and electric resistance of the cerebral cortex under the effects of strychnine and atropine]. AB - The effect of strychnine and atropine on the amplitude of the evoked potentials (EP) of the cerebral cortex was studied. It was shown, that both drugs increased amplitude of the EP. When we used strychnine, increased amplitude of the EP determined modification of the electrical resistance and current sources of the electrical field of the EP. Atropine did not change electrical resistance and in this case only electrical current sources determined modification of the EP. PMID- 1421247 TI - [Changes in the bioelectrical activity of the brain cortex in rats with infraorbital nerve compression]. AB - Bioelectrical activity of the somatosensory cortex was studied in the Wistar rats with chronic (1.5-2 months) compression of the infraorbital nerve produced by two partial ligations. In 20% of rats spike-slow wave complex and slow waves were observed. Electrostimulation of the skin on the injured nerve side resulted in a considerable increase in the amplitude of early components of the contralaterally evoked potentials in comparison with the non-injured side stimulation in 75% of rats. A decrease in the evoked potential thresholds on the injured nerve stimulation was shown in both hemispheres. In most of the animals a hypersynchronous late component of the evoked potential was observed. PMID- 1421246 TI - [Relationship between functional activity of the adrenal glands and gonads in monkeys during puberty]. AB - Testicular and adrenal cortex endocrine functions were simultaneously tested in pubertal baboons (papio hamadryas) during one year. Concentrations of androgens (testosterone, 5 alpha-dihydrotestosterone, dehydroepiandrosterone), corticosteroids (cortisol, progesterone, 17-hydroxyprogesterone, 17 hydroxypregnenolone) and aldosterone were determined in blood of the experimental monkeys by radioimmunoassay. It was shown that with increasing androgen (testosterone and dihydrotestosterone) levels in blood of the pubertal monkeys there was a significant decrease of corticosteroid concentration which was most pronounced in the monkeys with maximum increase of testosterone level. Described hormonal changes did not influence aldosterone concentration. PMID- 1421248 TI - [Mechanism of the antiarrhythmic effect of laser irradiation]. AB - Acute experiments were performed to study the role of afferent impulses from the heart receptors which pass by different vagal fibers during intraatrial laser irradiation. Double laser irradiation of the right atrium seemed more effective than a single one as to decreasing ventricular arrhythmias during cardiac ischemia. It is shown that the antiarrhythmic effect of intraatrial laser irradiation may be due to the change of the afferent information passing by myelinated vagal fibers. PMID- 1421249 TI - [Interatrial differences of myocardial reactivity and its changes in adaptation of rats to physical exercise]. AB - The myocardial reactivity to main regulatory influences (changes of stimulation rate, superfusion of acetylcholine, adrenaline, noradrenaline) was to be higher in right than in left rat atrium. The training-induced increase of some interatrial differences in myocardial reactivity suggests their essential physiological significance. PMID- 1421250 TI - [Effects of taurine and dipeptide Tyr-Tyr on ventricular defibrillation]. AB - Results of the study of taurine and dipeptide Tyr-Tyr effect on the threshold values of functional lesions of the myocardium and heart defibrillation are reported. The experiments were carried out on 27 narcotized mongrel dogs weighing 12-30 kg. Defibrillation was performed using Lifepak-7 defibrillator (USA). Lesion threshold (LT), defibrillation threshold (DT) and electrotherapeutic index (ETI) as a LT:DT ratio were determined. In 14 experiments (control group) these parameters were evaluated during 3 h. In group 1 (6 experiments) taurine (100 mg/kg) was infused intravenously by the end of the 1st hour, in group 2--Tyr-Tyr (25 mg/kg). It was shown that infusion of taurine did not have a noticeable effect of the LT, DT and ETI values. Infusion of Tyr-Tyr resulted in an increase in LT and DT. The possibility to use dipeptide Tyr-Tyr in the complex of measures aimed at ceasing ventricular fibrillation is discussed. PMID- 1421251 TI - [Role of the vagus nerve in mechanisms of the modulation of afferent duodenal effects]. AB - The electrostimulation of vagal nerves, the effect of naloxone and atropine on duodenal afferentation by registering evoked potential (EP) at cortex on direct electrostimulation of duodenum have been studied in acute experiments on cats. It has been established that the stimulation of afferent portion of vagal nerves causes the effect of deprivation of EP, whereas the stimulation with certain intensity of efferent portion of vagal nerves intensifies the duodenal afferentation. The effect of afferentation easeness (relief) has been blocked by the application of naloxone 10-20 microgram on duodenal bulbus, but not on it's i. v. injection and without effect on local application of atropine. It is concluded that the role of vagal nerves on the modulation of duodenal nociception is due to the activation of opiate terminals of the efferent vagal nerve portions. PMID- 1421252 TI - [Functional state of the endogenous opioid peptide system in traumatic shock in rats]. AB - The experiments have been performed on 120 Wistar rats and 546 CBWH mice. Met enkephalin (ME) and beta-endorphin (BE) levels were determined to increase in blood and mid-brain 3 hours later after soft tissue compression of pelvic extremities. 48 hours later after six-hour compression BE and ME level in blood was increased, BE concentration in blood was also increased, and enkephalins' content in brain and blood was decreased as against the control. Opioid peptides influence on the host compression period has been studied. D-agonists were established to decrease, but mu-agonists were established to increase mice survival in shock. Opioid peptides' significance in traumatic shock pathogenesis is being discussed. PMID- 1421253 TI - [Study of axodendritic synapses of the hippocampal CA3 field in experimental uremia and administration of exogenous parathyroid hormone]. AB - The effect of parathyroid hormone intraperitoneal injection at different stages of experimental uremia induced by subtotal nephrectomy on ultrastructural morphofunctional characteristics of hippocampus Ca3 field axospinal synapses was studied. A conclusion is made that the decrease of synaptic activity in the hippocampus field due to redistribution of calcium ions between spine cytoplasm and spine apparatus may take place after PTH injection and during uremia development. PMID- 1421254 TI - [Effects of calcium antagonist finoptin on superoxide dismutase activity and conditioned reflex memory in adrenergic cardiac necroso-genic stress in rats]. PMID- 1421255 TI - [Effects of prolonged hyperbarism on lipid peroxidation and structural-functional state of erythrocytes]. AB - Prolonged helium-oxygen hyperbaric (pressure 3,6 MPa) increased diene conjugate and Schiff's base level in plasma and erythrocyte membranes of mice. In those conditions SOD and glucose 6-phosphate dehydrogenase activities were inhibited in erythrocytes. Lipid bilayer microviscosity and cholesterol content of erythrocyte membranes were increased. PMID- 1421256 TI - [Antiatherogenic action of corn oil in experimental atherosclerosis]. AB - Therapeutic effect of corn oil was studied in rabbits with alimentary atherosclerosis. Corn oil was administered (2 ml/kg, 30 days) after the completion of cholesterol diet unlike studies, where they were administered simultaneously. Total cholesterol, apoB-lipoprotein cholesterol and triglycerides decreased more intensively in rabbits fed by corn oil than in control group. No changes in high-density lipoprotein cholesterol were observed. The most pronounced effect was noted in aorta morphological analysis: an aorta damage degree was 4.8% as compared with 52.9% in the control group. The results show that available plant oils with omega-6 polyunsaturated fatty acids (PUFA), in particular corn oil, may as well as omega-3 PUFA be used as the base for antiatherogenic preparations. PMID- 1421257 TI - [Antiradical activity of complex copper compounds (II) on coumarin ligand base]. AB - The antioxidant capacity of copper chelates with coumarins has been studied by the method of iron-induced chemiluminescence. All substrates studied were potent antioxidants, comparable to butylated hydroxytoluene. The mechanism of the antioxidant action of these copper-coumarin chelates was similar to that of Cu-Mn superoxide dismutase, with a coumarin part of the complex being involved as a free radicals trap. PMID- 1421258 TI - [Content of cholesterol extracted from human skin surface--a possible discriminant of atherosclerosis?]. AB - Basing on the data of Bouissou et al. on an increase of cholesterol content in the skin biopsies in atherosclerosis patients, the cholesterol amount was evaluated after superficial atraumatic rapid treatment of patients palm skin. The optimization of the extraction conditions was performed: the surface skin cholesterol value was constant for individual subjects (variability factor 5%). The range of this value was 1.5-6 Mg/cm2 and it was higher for atherosclerotic patients. No correlations with any conventional plasma lipoprotein parameters were observed. At the same time positive correlation (r = 0.54. p < 0.01) was observed with dyslipoprotein coefficient--(Ch+TG/alpha-Ch). Possible diagnostic significance of this skin cholesterol parameter is discussed. PMID- 1421259 TI - [Relaxant effects of oligopeptides isolated from the tracheal mucosa and pulmonary parenchyma on the smooth muscle of isolated rat trachea]. AB - Relaxant effect of oligopeptides extracted from tracheal mucosa (PTM), lung parenchyma (PLP), aortal wall (PAW) and thymic gland (PTG) was investigated using acetylcholine-induced constriction of tracheal strips. Time of 50 percent relaxation of constricted strips treated with saline, atropine or peptides was measured. Both PTM and PLP in concentrations 10(-6)-10(-3) g/ml accelerated relaxation in dose-dependent manner, however this effect was less prominent compared with atropine. Relaxant effect of PTM was found using different parts of trachea (cervical of thoracal), indicating independence of PTM action of intramural ganglia which are present only in the thoracal part. PAW and PTG did not show any significant effect on relaxation time. These results suggest the presence of oligopeptides, capable to relax airways smooth muscle, in tracheal mucosa and lung parenchyma. PMID- 1421260 TI - [Increased lipid peroxidation in the rat hypothalamus after short-term emotional stress]. AB - Concentrations of TBA-reactive substances (TBARS) were measured spectrophotometrically in homogenates of small samples of the brain (hypothalamus, parieto-occipital, sensori-motor and limbic cortex), heart, liver and adrenals of male August and Wistar rats; the former strain is more susceptible to emotional stress than the latter one. Forced isolation of the rats in the restraining plastic cages for 1 h increased the TBARS concentrations in the hypothalamus and liver in August rats only. TBARS accumulation in some tissues correlated with such indices of emotional stress as the changes in relative weight of thymus and adrenals. As regards the brain regions, after 1 hour emotional stress the TBARS levels were no longer different because of an increment in hypothalamic TBARS concentration. However, in control conditions the hypothalamus had significantly lower TBARS levels than any other brain structure both in Wistar and August rats. PMID- 1421261 TI - [Role of leukocyte adhesion in filterability of blood cell suspensions]. AB - We investigated blood cells suspension filterability of 16 donors. The filtration was performed trough 5 microns-pore nuclear filters at constant perfusion pressure 10(5) din/cm2. We estimated also the adherence of leukocytes and platelets on nylon. The adherence of platelets and mononuclear leukocytes reduced the level of the suspension filterability only by 21% (p > 0.05). The presence of nonadhesive polynuclear leukocytes in the suspensions did not change practically their filterability. The addition in the suspensions of adhesive polynuclear leukocytes reduced suspension filterability dramatically. PMID- 1421262 TI - [Effects of peginol C-2000 on respiration and oxidative phosphorylation in liver mitochondria of rats poisoned with butylcaptax]. AB - The data on the effect of synthetic antioxidant Paginol C-2000 on respiration and oxidative phosphorylation in liver mitochondria of rats primed with butylcaptax are given. It is shown that intoxication of organism with butylcaptax in the dose of 1/10 LD50 during 5 days resulted in suppression of respiration and oxidative phosphorylation in rat liver mitochondria. It is found, that administration of Raginol C-2000 into organisms of primed animals leads to the reduction of succinate pathway of oxidation, that, in its turn, results in the normalization of functioning level of ATP-synthesizing system of mitochondria. PMID- 1421263 TI - [DNA-protein interactions in CpG islands and DNAse I sensitive chromatin]. AB - DNA-protein interactions were studied in the chromatin preparations obtained according to different procedures by means of nucleoprotein-celite chromatography. Three discrete fractions dissociating in 1M, 2M and 3M NaCl were observed in all preparations. The 1M fraction prevails in DNaseI-sensitive chromatin and the 2M fraction--in the resistant. Chromatin solubilized by MspI restrictase (the active chromatin) contains the 1M and 3M fractions, one solubilized by AluI (inactive)--the 2M fraction. Distribution of the fractions is different in proliferating and quiescent cells. PMID- 1421264 TI - [Post-intoxication hypothermia and processes of free radical lipid peroxidation in the rat brain and heart in organophosphorus cholinesterase inhibitor poisoning]. AB - The activity of lipid peroxidation (LP) of the brain and myocardium as well as the intensity of the body hypothermia during 30 days after a single introduction of poisons at a dose < D50 were studied on the models of induced toxicosis in rats due to two organophosphorus compounds (malathion and armin). It has been established that the maximums of diene conjugates and Schiff's bases accumulation in the rat organs poisoned with malathion and the intensity of hypothermic response on days 14 and 21 after intoxication coincided. The similar elevated lipid peroxidation was associated with esophageal hypothermia on day 14 after armin administration. Therefore, because of hypothermia, the influence of organophosphorus compounds on lipids of the rat brain and heart in the post intoxication period may include the free radical ways of their peroxidation. PMID- 1421265 TI - [Lipid peroxidation in the aorta of normotensive and spontaneously hypertensive rats with diabetes mellitus]. AB - We have studied the effects of streptozotocin-induced (STI) diabetes on the lipid peroxidation in the aorta from normotensive (NTR) and spontaneously hypertensive (SHR) rats. In the control SHR quantity of malonyldialdehyde (MDA), conjugated dienes (CD) and arterial pressure where higher than in NTR analogous group. It has been shown that Diabetes in NTR results in significantly increased arterial pressure and quantity of MDA and CD. Under certain conditions in SHR arterial pressure and the other factors remain almost unchanged. It is likely that completely different changes in intensity of lipid peroxidation may evidence breaking adaptation mechanism in diabetic SHR. PMID- 1421266 TI - [Effects of arginine on properties of the erythrocyte membrane in hypoxia]. AB - The antioxidant effect of arginine evident from stabilization of membrane structure and properties and activation of oxygen-toxicity-protecting enzymes was demonstrated in hypoxia. The intraperitoneal injection of L-arginine-HCl in a dose of 120 mg per 100 g body mass prevented the increase of microviscosity, membrane permeability and lipid peroxidation products level in hypoxia. At the same time the activity of the antioxidant enzymes--superoxide dismutase and catalase--was increased in red blood cells by 64 and 46%, respectively. PMID- 1421267 TI - [Activity of cytochromes P-450p and P-450h in liver microsomes and blood corticosteroid levels in experimental animals under the action of physical factors]. AB - In experiments on male Wistar rats it has been found that physical factors applied in medicine (laser radiation of low intensity with wave length 0.89 microns, microwaves of centimeter range of 2450 MHz, and ultrasound of low intensity 880 KHz) changed catalytic activity of liver microsomal and rostenedione 16 alpha- and 6 beta-hydroxylating cytochromes P-450h and P-450p and blood corticosteroids level. Activities of these two steroid-metabolizing cytochromes decreased under ultrasonic skin application on liver region and increased under microwave and laser action. Contents of physiologically inactive form of corticosterone were not changed by the physical factors action while level of active hormone was increased under ultrasonic and microwave action. These findings suggest association of the activity of liver steroid-metabolizing cytochromes P-450 and level of physiologically active form of corticosterone in blood under physical factors skin application on liver region. PMID- 1421268 TI - [Lipid peroxidation changes in the brain in fetal alcohol syndrome]. AB - The study was performed upon three groups of 12-week-old male rats. The first group of rats received ethanol/9 g/kg/day as 6% aqueous solution/during pregnancy and lactation, the second group received ethanol only during lactation and the third group, controls, received equicaloric sucrose solution. The concentrations of LPO products were determined in the homogenates of tissue from frontal cortex, striatum, hypothalamus, hippocamp and cerebellum. The concentration of fluorescent products in the brain structures of rats treated perinatally with ethanol was several-fold increased as compared with controls. The levels of diene conjugates were increased in most brain structures of rats with FAS. It should be pointed out that there was the same degree of increase of the levels of both fluorescent products and diene conjugates in two groups of rats with FAS. Having in mind that in the rat the increased growth of the brain occurs during the first 10 postnatal days, it might be assumed that this period is favorable for LPO. PMID- 1421269 TI - [Anticalcium activity of several antidepressive agents]. AB - In experiments in white mice and rats the antidepressants pyrazidol (pirlindole), moclobemide and especially tetrindole possess anticalcium activity in tests of calcium chloride-induced lethality in mice and arrhythmia in rats. Tetrindole is as active as verapamil. Imipramine, azaphen and incazane were not active in these experiments. In vitro on isolated intestinal segments of guinea-pigs tetrindole exerts anticalcium action, but in less degree than verapamil. In all probability the anticalcium activity of tetrindole may play some role in the mechanism of action of this compound on the central nervous system. PMID- 1421270 TI - [Antioxidant effects of antihypoxic drugs in cerebral ischemia]. AB - Cerebral ischemia in rats (both carotid arteries occlusion) during 30 min, 3 hours and recirculation (1 hour) after ischemia (30 min) stimulated diene conjugates and fluorescent products accumulation in brain tissue. Intraperitoneal injection of sodium hydroxybutyrate (100 mg/kg), bemitil (50 mg/kg), ethomersol (50 mg/kg) reduced brain lipid peroxidation and did not yield in this respect to emoxypin (5 mg/kg). In contrast to emoxypin, sodium hydroxybutyrate, bemitil and ethomersol had no antiradical activity. PMID- 1421271 TI - [Participation of protein synthesis in brain cell structures in the action of antifeins on long-term memory]. AB - Incorporation of 3H-leucine into proteins of rat brain cell structures during application of antifeins (compounds of alternative action on memory processes) has been studied. No correlation was observed between changes in protein synthesis in nuclei, mitochondria, components of endoplasmic reticulum and memory effects of ethyl-, allyl- and propylnorantifeins. Only M1 and M2-demethylated structural analogs of ethylnorantifeins (exerting the most effective action on RNA synthesis and retention of conditional reflexes) enhanced the synaptosomal protein synthesis. PMID- 1421272 TI - [Analysis of the role of calcium in analgesic action of non-narcotic analgesics and calcium channel blockers]. AB - In the mice hot-plate test we have compared analgesic effect of calcium channel blockers and new non-narcotic analgesic antiinflammatory agent PV-107: verapamil > fenigidin > PV-107. Simultaneously we have shown strong correlation (r - 0.82) between analgesic effect and 45Ca2+ efflux of cardiac membrane in depolarizing media in vitro. PMID- 1421273 TI - [Mechanism of prolonged hypocoagulation appearing after intratracheal administration of heparin]. AB - The comparative study of intratracheal and intravenous effect of administration of heparin on blood clotting and mast cell population condition was carried out in experiments. Unlike intravenous bolus injection of heparin, which induced fast short-time inactivation of all enzyme clotting factors, a single intratracheal injection inactivated "internal" rout of thrombin production. It was shown, that long-term hypocoagulability effect and inhibition of factors of blood coagulation after intratracheal administration of heparin correlated with accumulation of heparin in mast cell. PMID- 1421274 TI - [Detection of opioids in an extract of oak silkworm cocoons]. PMID- 1421275 TI - [Role of T-lymphocytes in the mechanisms of hemopoiesis-inducing microenvironment activation in inflammation]. AB - On the model of acute infectious peritonitis in mice, the inflammation was shown to accompany pronounced activation of bone marrow haemopoiesis. The increased number of committed precursor cells of erythro- and granulomonocytopoiesis, morphologically differentiated elements and enhancing colony-stimulating and erythropoietic activities of GIM cells origin were shown as well. Thy 1.2+ cells, migrating to bone marrow, were shown to play an important role in hemopoiesis stimulation inflammation. These stimulate the processes of myeloid precursor proliferation directly (by means of lymphokines) and in cooperation with monocytes-macrophages of GIM. PMID- 1421276 TI - [Characteristics of the mitogenic activity of purified thymocyte growth factor]. AB - Being purified by gel filtration and reverse phase HPLC the thymocyte growth factor from the supernatant of the cell line of intrathymic precursors of T lymphocytes can stimulate the growth of splenocytes and thymocytes nonactivated by mitogen. Addition of suboptimal doses of mitogen or phorbol myristate acetate does not enhance the cell response to the thymocyte growth factor. The thymocyte growth factor in capable of stimulating the growth of thymocytes synergistically with interleukin-2, but the direct action of the thymocyte growth factor is not mediated by the production and reception of interleukin-2 and interleukin-4. PMID- 1421277 TI - [A simple method of continuous passage of human tumors in immunocompetent mice]. AB - A simple procedure is described for the continuous passage of a human tumor in immunocompetent mice. The BRO human melanoma was transplanted consecutively 25 times by implanting tumor tissue under the sub--renal capsule of mice which had been immunosuppressed by a single dose of whole--body irradiation or by cytosine arabinoside followed by irradiation. The tumor grew continuously for 14 days, and cytological examination showed that the growth consisted almost entirely of tumor cells. PMID- 1421278 TI - [Immunomodulating activity of exogenous ceruloplasmin in experimental tumor growth]. AB - Immunomodulating properties of ceruloplasmin were determined in vivo on healthy mice line C57BL/6 and mice with Lewis carcinoma. It was established, that ceruloplasmin at the concentration of 1-40 mg/kg stimulated both T- and B- systems of immunity and prevented immunodepression activity of tumor growth. PMID- 1421279 TI - [Inhibition of phospholipid reacylation in oxidative damage of tumor cells]. AB - In this study we examined the effect of oxidative stress on phospholipid reacylation and [1-14C]arachidonic acid uptake by murine mastocytoma P815 cells. Tert-butyl hydroperoxide inhibited arachidonic acid uptake by P815 cells and incorporation of fatty acid into main cellular phospholipids. Specific activity of control phosphatidylcholine was about 15-fold higher than that of phosphatidylcholine from tert-butyl hydroperoxide-treated cells. For phosphatidylethanolamine and phosphatidylinositol this inhibition was about 7 fold and 12-fold, respectively. Thus, oxidative stress causes the drastic changes in the process of phospholipid repair, which may significantly disorder membrane stability. PMID- 1421280 TI - [Effects of human defensin HNP-1 on the production of tumor necrosis factor-alpha by human blood monocytes in vitro]. AB - The influence of human defensin HNP-1 on the synthesis of tumor necrosis factor alpha (TNF-alpha) by human blood monocytes was studied. It was shown that TNF alpha production by human monocytes activated by SAC or PMA was augmented in the presence of HNP-1 concentrations of 10(-8)-10(-9) M. HNP-1 alone induced no synthesis of TNF-alpha. High concentration of HNP-1 (10(-4) M) was cytotoxic for human monocytes. PMID- 1421281 TI - [Electrophoretic analysis of 53K protein presence in leukocytes of the newborn]. PMID- 1421282 TI - [Thiol-induced fragmentation of chromosomal DNA]. AB - Supramolecular complexes of DNA (SC DNA) were isolated from loach sperm, loach erythrocytes and hen erythrocytes by the phenol method. By the use of UV sedimentation on neutral 5-20% sucrose gradient, we studied the effect of 2 mercaptoethanol (ME), dithiothreitol (DTT) and NaBH4 on SC DNA at different pH and long-time incubation (5 and 10 days). It appeared that ME treatment at pH 4.4 fragmented SC DNA of three objects into subunits of size 5 x 10(5)D. Incubation with DTT at pH 8 in the presence of EDTA resulted in subunits of size 1-2 x 10(7)D. However, NaBH4 at pH 8 failed to induce fragmentation of SC DNA. It is shown that ME-induced at pH 4.4 fragmentation is accompanied by a decrease in hyperchromatic effect of subunits, indicating the presence of "sticky" ends. Thus, ME-induced fragmentation of SC DNA results from a "clayting" double-strand break, involving, on an average, 180 bp. PMID- 1421283 TI - [Delayed hypersensitivity to house dust-storage mites Thyrophagus putrescentiae in experimental allergic dermatoses]. AB - House dust mites and storage mites proved to be one of the main allergens causing hypersensitivity in atopic dermatitis in allergic patients. The authors reproduced experimental allergic dermatosis on the model of delayed type hypersensitivity in guinea pigs, caused by sensitization to the allergen from the mite's bodies Tyrophagus putrescentiae--species having wide distribution in the country. The results characteristic for T-cell type hypersensitivity have been obtained: delayed positive skin tests after 24 hours, typical histomorphological picture (strong allergic alteration, epidermis desquamation, vasculitis, dermis T cell infiltration and spongiosis--Waksman's syndrome). It is concluded that side by side with humoral IgE-mediated reaction there is strong delayed T-cell hypersensitivity to the storage mites Tyrophagus putrescentiae. PMID- 1421284 TI - [Testing of promising dressing materials in cultures of fibroblasts and keratinocytes of human skin]. AB - Cell cultures of epidermal keratinocytes and dermal fibroblasts were used to test collagen dressings in vitro. It was shown that effects of the dressings on skin major cell types might be differentially evaluated. PMID- 1421285 TI - [Clinico-experimental study of histoenzymological changes in the ventricular myocardium in pulmonary embolism]. AB - The SDH and LDH activity in ventricular myocardium was studied in early autopsies of 16 patients, which died from acute pulmonary thromboembolism, and also in 17 dogs with experimental pulmonary embolism. In general the data of histoenzymological study of experimental and sectional material were identical. We revealed some factors, which correlated with low activity of catabolic enzymes in ventricular myocardium of the patients with pulmonary embolism: small volume of embolic occlusion (the thromboembolism of lobar and segmental pulmonary arteries); the presence of prior chronic cardiopulmonary disease; the advanced age and the female sex. Preexisting cardiopulmonary disease, as well as age and sex changes of myocardial metabolism, may assist the development of heart failure by relatively small volume of embolic obstruction. PMID- 1421286 TI - [Development of interfollicular epidermis on the surface of collagen framework of the dermis in experimental animals]. AB - The fate of interfollicular epidermis keratinocytes which filled the hair follicles bursas of collagen dermis framework was investigated in the autotransplantation experiment. Collagen dermis framework was prepared from the skin flap. Interfollicular epidermis was detached with the help of suction method and transferred to the collagen dermis framework surface which was placed previously on the full thickness skin defect surface. It was established that in this environment keratinocytes not only developed, but some of them migrated into the hair follicle bursas cavities. It resulted in the follicular-like structures formation, cell elements of which differentiated in the manner characteristic of interfollicular epidermis. However, in spite of the fact that the epidermal cells partially retained their proliferating ability, ingrowing would completely disappear by the 15th to 20th day after the transplantation. PMID- 1421287 TI - [Effects of antibodies to lysosomal enzymes on the course of experimental burn shock]. AB - On the model of burn shock in rats, the influence of antibodies to lysosomal enzymes has been studied in respect to the cathepsin D activity, oxygen regimen, acid-base equilibrium in blood, and animal survival. It has been shown that the antibodies inactivate the cathepsin D activity which is increased in burn shock. Because of the decreased cardiodepressant action of the lysosomal enzymes, the blood circulation improves, the manifestations of hypoxia and metabolic acidosis are attenuated. The results obtained confirm an important role of the lysosomal in the pathogenesis of bur, shock and permit one to consider its therapy using antibodies to the lysosomal enzymes to be promising. PMID- 1421288 TI - [Flavobion and thioctacid lessen irradiation-induced latent injury of the liver]. AB - The effect of hepatoprotective drugs (flavobion and thioctacid) and a single whole-body irradiation (5.7 Gy of gamma radiation) on the regeneration of rat liver was examined. Liver regeneration was estimated on the basis of chosen morphological parameters on hour 30 after partial hepatectomy. Radiation-induced latent injury to intact rat liver 30 min before partial hepatectomy manifested in remaining regenerating liver by slowing-down of the increase in liver weight, cellularity and inhibition of the mitotic activity and in more frequent chromosome aberrations. Both hepatoprotective agents, especially thioctacid, used i.p. 60 min before irradiation, i.e. 90 min before partial hepatectomy, alleviate the manifestations of latent injury in this low proliferating organ as indicated by an increase in cellularity and mitotic index as compared with unprotected animals. Furthermore, the preparations tested decreased the frequency of radiation-induced chromosome aberrations. PMID- 1421289 TI - [Ultrastructural changes in interneuron connections in intramural ganglia of the small intestine in suckling rabbits with experimental cholera]. AB - Data, received in investigation of the small intestine intramural ganglia of 34 suckling rabbits show, that development of experimental cholera induce in the neurons reactive shifts, changed by dystrophic alterations. Prevaluation of cholinergic influences in autonomic ganglia in small intestine promotes enterocytes hypersecretion and accelerating of motor activity. PMID- 1421290 TI - [Functional morphology of resistant pulmonary vessels and capillaries in individual and species adaptation to high altitude]. AB - Morphological and structural rearrangement of resistant pulmonary vessels and alveolar capillaries was assessed in lowland animals (rabbits) during high altitude adaptation, in aboriginal high-altitude species (yaks, mountain goats) and on native highlanders. Structural adaptive developments in pulmonary vessels and capillaries of high-altitude animals contribute to maximal facilitation of gas diffusion. Similar adaptive changes in pulmonary resistant vessels and capillaries of laboratory animals and in native highlanders are associated with pathological alterations manifest in the elevation of pulmonary vascular resistance, right ventricular hypertrophy, increases in the thickness of the basal membrane of the air-blood barrier. In all the subjects studied the process of high-altitude adaptation is associated with hypertrophy of pulmonary endothelium. The intensification of pulmonary endothelium. The intensification of pulmonary endothelium metabolic activity may be directed at regulation of vascular tone. PMID- 1421291 TI - [Changes in adhesive interactions of keratinocytes during regeneration of the rat skin]. AB - The values of adhesion between keratinocytes as dermo-epidermal junction in the skin decreased after UV-irradiation, heating to 60 degrees C or sodium dodecyl sulfate action. The results suggest the existence of nonspecific adaptive reactions of keratinocytes adhesive interactions in response to different irritative stimulants. PMID- 1421292 TI - [Reparative changes in the sensorimotor cortex of the offspring in moderate prenatal alcoholism]. AB - Sensorimotor cortex of 21-, 30-, 60-day-old offspring given prenatally moderate alcohol (2 g/kg) manifested signs of compensatory type: double nerve and glial cells, open capillaries, nearby nerve and glial cell bodies with basal membrane of capillaries. Intracellular reparative processes in dystrophic neurons were observed: nuclear activation, hyperplasia of cytoplasmic organelles, hypertrophy of some of them. Reparative processes are more distinct in 30-day-old rat offspring In 60-day-old offspring a polymorphic pattern of cortical synapses ultrastructure was found. However, dystrophic changes of neurons and interneuronal connections still remain. PMID- 1421293 TI - [A new method of assessing anxiety-phobic states in rats]. AB - A new multiparameter method for evaluating anxiety-phobic states in rats is elaborated. The method is based on the ranged scale consisting of parameters which characterize the species-specific rat response to the series of ethologically adequate test-stimuli inducing manifestation of the anxiety-phobic states. The method makes it possible to evaluate individual anxiety-phobic level in rats, to form experimental groups with rats of known individual anxiety-phobic level, to conduct repeated observations in the same animals. The method is easy to perform in laboratory and makes it possible to get the results quickly. PMID- 1421294 TI - [Opposite effects on antioxidant enzymes of adaptation to continuous and intermittent hypoxia]. AB - Adaptation to continuous hypoxia under mid-mountain conditions (altitude 2100 m) decreases the content of lipid peroxidation products and the activity of superoxide dismutase and catalase in rat heart, liver, and brain, with a concomitant decline in the resistance to reperfusion arrhythmias. On the contrary, adaptation to intermittent hypoxia in the altitude chamber increases the activity of the antioxidant enzymes in the same organs, while the content of peroxidation products remains normal; at the same time, the heart becomes more resistant to reperfusion arrhythmias. The mechanism is discussed that ensures enhanced antioxidant protection in adaptation to intermittent hypoxia. PMID- 1421295 TI - [Effectiveness of artificial ventilation in oil microembolism followed by pulmonary edema]. AB - In experiments on sodium pentobarbital (40 mg/kg, i.p.) anesthetized mongrel cats of either sex weighting from 2.0 to 4.0 kg, it was found, that in conditions of oil pulmonary microembolization, followed by pulmonary edema, the most suitable is rapid and shallow pattern of ventilation, ensuring optimal ventilation/perfusion interrelation. The oil microembolization was introduced with intravenous administration (1 mg per kg of body weight during 2 min) of olive oil. It is necessary to provide flexible regimens of artificial ventilation and conformity of respiratory pattern and body's demands can be controlled according to pHa and PaO2. It is desirable that pH and pO2 can be evaluated continuously. PMID- 1421296 TI - [Dynamics of coronary circulation in rats]. AB - The blood flow velocities in left anterior descending coronary artery and ascending aorta have been measured in anesthetized rats by high frequency Doppler technique. The measurement of coronary blood flow velocity by miniature ultrasonic probe (2.0 x 1.5 mm) was performed through myocardial surface. Two different forms of coronary blood flow curves were recorded. These forms of the curves depend on the value of the coronary blood flow velocity and are connected with the ascending aorta blood flow velocity. The dynamics of the coronary blood flow reactions under coronary artery occlusion and asphyxia in the rat is similar to the one in the cat and the dog, but less expressive. In experiments with vasodilators the direct dependence between linear and volume coronary artery velocities under the measurement through myocardial surface was found. PMID- 1421297 TI - [Functional state of the hematopoietic system in different stages of CCL4-induced liver fibrosis in mice]. AB - The state of hemopoietic system at different stages of CCL4-induced liver fibrosis in mice and its reaction to stimuli was examined. At early stages of liver fibrosis (2 weeks of CCL4-administration) we observed a disinhibition of granulo-monocytopoiesis. This is manifested in an increase of the number of immature granulocytes, monocytes/macrophages and CFU-GM in the bone marrow. After 24 h of zymosan injection in this stage an increase of both bone marrow CFU-GM and CFU-E, and the rate of serum colony stimulating activity (CSA) occurred. On the contrary, in advanced liver fibrosis (16 weeks of CCL4 administration), the rate of both granulo-monocytopoiesis and erythropoiesis were decreased as compared with the preceding stage of the process and the response to zymosan became perverted: the number of CFU-GM was paradoxically decreased, while the number of CFU-E remained practically unchanged. The rate of serum CSA increased very poorly too. Thus, in advanced liver fibrosis the hemopoietic system is functionally defective and this factor may be important in development of fibrotic process in the liver. PMID- 1421298 TI - [An experimental model of apneusis and periodic respiration]. AB - In experiments on sodium pentobarbital (40 mg/kg, i. p.) anesthetized mongrel cats of either sex weighting from 2.0 to 4.0 kg, it was stated, that sodium or lithium hydroxybutyrate (HOB) (200 mg/kg, i. v.) effectively slowed down breathing with inspiratory holdings. Thus 3-5 minutes after HOB administration, eupneic pattern of respiration was changed firstly to inspiratory apneustic one (100% of cats), and then to periodic one (80% of cats). This pattern persisted for 60-90 minutes, and after that the respiratory pattern usually changed its direction to the opposite one. In these conditions alterations of arterial blood composition (pH, pO2, pCO2, SO2) and hemodynamic variables (heart rate, arterial pressure) can not be considered as the cause of apneustic pattern of respiration. It is suggested, that HOB can be used for simulating such terminal respiratory patterns as apneustic and periodic ones. PMID- 1421299 TI - [Aldosterone and electrolyte content in blood and myocardium of rats after single physical load in acute alcoholic intoxication]. AB - It is shown that acute alcoholic intoxication causes essential changes of aldosterone content and balance of electrolytes in blood plasma of Wistar rat males. The SPL test revealed the inadequate reaction in the mineral-corticoid function of the adrenal glands in the rats with acute alcoholic intoxication. The method of the free choice of the load by the experimental rats is the most optimal way to assess. The rats with acute alcoholic intoxication displayed smaller tolerance to physical load. PMID- 1421300 TI - [Organization of reflex sympathetic influence on rate and force of cardiac contraction]. AB - In acute experiments on 21 cats it was proved that the change of afferent impulse on vagus nerves by means of either freeze-block or electrostimulation of their central ends results in differential reflex influences on rhythm and force of the cardiac contractions caused by sympathetic nervous system. The cut of the lower cardiac nerves may cause 'break-up' of the observed reflex, removing or inverting its ino- or chronotropy component. The given phenomenon was revealed in the experiments with high arterial pressure and with absence of tonic chronotropy influences of the left lower cardiac nerve. PMID- 1421301 TI - [Effects of inflammation on adhesive interactions of keratinocytes]. AB - The reversible prolonged increase of intercellular adhesion in the epidermis along the margins of the wound as well as in the scar epidermis during the full thickness skin wound healing was found. This effect must have adaptive significance. PMID- 1421302 TI - [Quantitative characteristics of interactions of blood lipoproteins and steroid hormones]. AB - Human and serum lipoproteins interaction with steroid hormones (corticosterone and hydrocortisone) were studied. Methods of fluorescence quenching titration and equilibrium dialysis were used for quantitative evaluation of VLDL, LDL and HDL glucocorticoids binding ability. Association constants were found to be 0.6-2.0 x 10 M for corticosterone and 4.0-8.0 x 10 M for hydrocortisone. The number of binding sites ranged from 3 to 300 for different classes of lipoproteins. Our data suggest high specificity of serum lipoproteins binding with corticosterone and hydrocortisone. PMID- 1421303 TI - [Nuclear magnetic relaxation in biochemical analysis of plasma and blood serum]. PMID- 1421304 TI - [Antioxidant activity of high density lipoproteins in vivo]. AB - The paper deals with antioxidant effect of high density lipoproteins (HDL) in vivo. The effect of intravenous injection of large-dose HDL3 (200 mg protein), isolated from human plasma to rabbits with experimental hypercholesterolemia, on the content of primary products of lipid peroxidation in rabbit blood, the correlation between HDL cholesterol level and the content of lipid peroxide products in blood plasma of healthy persons and patients with IHD were studied. Intravenous injection of HDL3 to rabbits with experimental hypercholesterolemia has been shown to lead in 6 hr to a 24-hr significant (p < 0.01) decrease of conjugated dienes and trienes. The existence of negative correlation between HDL cholesterol level and the content of conjugated dienes in blood plasma of healthy persons (N = 47) and patients with IHD (n = 64) is revealed. Basing on the data obtained conclusion of universal character of protective antiatherogenic effect of HDL is drawn. PMID- 1421305 TI - [Activation of free radicals reaction and changes in the state of antioxidant protection in blood in toxic experimental influenza infection]. AB - The paper presents an experimental model of toxic influenza infection. The toxic form of influenza was shown to result in the activation of free radical processes accompanied by the accumulation of both lipid peroxidation products and methemoglobin and the decrease of alpha-tocopherol in erythrocytes, by the accumulation of NO. and nitrizyl complexes of heme iron in the blood. The activation of free radical processes was followed by the stimulation of antioxidant system in the blood. Thus, there was an increase of both superoxide dismutase activity in erythrocytes and ceruloplasmin content in the blood. The data obtained support the important role of the active products of free radical processes in the development of toxicosis under acute virus infections. PMID- 1421306 TI - [Microsomal hydroxylating system of the mouse liver in toxic forms of influenza infection]. AB - The paper presents the experimental model of toxic influenza infection induced by A/Victory/35/72 (H3N2) strain adapted to CBA mice. The virus toxicosis was shown by means of ESR technique to be accompanied by a decrease of both the content of the active form of cytochrome P-450 and the activity of p-nitroanisole o demethylase. In microsomes there was activation of lipid peroxidation (LP) and an increase of microviscosity of lipid matrix. LP activation in microsomes was not accompanied by the change of alpha-tocopherol content. PMID- 1421307 TI - [Effects of cerebrocrast on local cerebral circulation and EEG in cats with cerebral hemorrhage]. AB - In experiments on awake cats before and after intracerebral hemorrhage influence of cerebrocrast and nimodipine intravenous infusion (1 microgram/kg-1/min-1 during 60 min) on cerebral blood flow (CBF) in the cortex, thalamus and reticular formation and power of (alpha + beta)-, theta-, and delta-waves was investigated. During cerebrocrast infusion increasing CBF and improving bioelectrical activity were demonstrated. PMID- 1421308 TI - [Dynamics of calmodulin in cerebral structures under the action of modulated UHF electromagnetic fields]. AB - The influence of modulated UHF-electromagnetic fields (low intensity) on calmodulin levels in several brain structures was studied. It was shown that UHF electromagnetic fields influence calmodulin levels in the hypothalamus and sensorimotor cortex. Its effect depends on modulation regimes. PMID- 1421309 TI - [Activation of ATP-sensitive K+-channels of cardiomyocytes by endogenous cardiopeptides]. AB - The "patch-clamp" method was applied to rat ventricular cardiomyocytes to study the effect of endogenous cardiopeptides (a component of a cardiologic medicine "cardialin") on single K(+)-channel currents. It was noted that ATP-sensitive K(+)-channel activity increased only in the presence of 10(-8)-10(-6) mg.ml-1 peptide solution in the patch-clamp micropipette. To check up the suggestion that G-protein takes part in a direct reaction of K(+)-channel by external ligand we studied the effect of GTP-gamma-S (0.1 mM) in the presence of Mg2+ (1 mM) on the K(+)-channel in "run-down" state in the "inside-out" configuration. It was demonstrated experimentally that reactivation of the ATP-sensitive K(+)-channel develops in the presence of GTP-analogue. PMID- 1421310 TI - [Prolonged action of tuftsin in penicillin epilepsy]. AB - The free behaviour experiments on rats showed during the first day the tuftsin induced (0.3 mg/kg i. p.) increment of epileptic discharge in all the structures simultaneously. Open field behaviour depended on the sequence of penicillin and tuftsin injections. The rats with tuftsin used after the epileptiformic activity has been developed showed the behaviour analogical to the penicillin-injected animals. The preventive injections of tuftsin resulted in restoration of all behavioural indications by the third day. The optimal corrective effect has been obtained with tuftsin used preventively. PMID- 1421311 TI - [Mechanisms of hepatoprotective action of new nicotinic acid derivatives in experimental CCL4-induced liver injury]. AB - New biologically active compounds (BAC) created on the basis of nicotinic acid possess hepatoprotective action. The preparations were introduced preventively in doses of 10 mg/kg during 14 days. Litonit and nicogamol increased survival of experimental animals by 36.8% and nicotinic acid by 26.8%. ALT, AST, GGT activity in the blood serum was reduced. The activity of the main antioxidant enzymes (SOD and catalase) grew in the rat liver tissue in parallel with inhibition of DK and MDA activity. Morphological picture of the rat liver, most evident after application of litonit improved. Hepatoprotective action of these BAC are attributed to their membrano stabilizing effects. PMID- 1421312 TI - [Non-quantal secretion of a mediator as factor determining consequences of acetylcholinesterase inhibition]. AB - The mechanism of shortening MEPC decay phase after initial prolongation due to acetylcholinesterase inhibition by armine and neostigmine was studied by use of two-electrode voltage-clamp at the mice diaphragm Factors which switch off non quantal secretion of acetylcholine from the nerve (acute denervation in vitro, ouabain, high concentration of magnesium ions) only slightly reduced the prolongation of MEPC caused by AChE inhibition. So, postsynaptic potentiation of MEPC by nonquantal ACh is not significant immediately after AChE inhibition. At the same time these factors abolished the process of shortening MEPC decay phase. It is concluded, that desensitization of the postsynaptic membrane induced by nonquantal ACh is the main mechanism of the MEPC shortening and that this mechanism can compensate insufficient AChE activity. PMID- 1421313 TI - [Development and use of a method of determination of specific immunoglobulin G based on immunoenzyme analysis in the diagnosis of pulmonary aspergillosis]. AB - Enzyme-linked immunoassay (ELISA) was employed for determination of specific immunoglobulin G to Aspergillus fumigatus (A.f.). Culture filtrate of A.f. was used as antigen. Optimal conditions of ELISA were found. Serum of 138 asthmatic patients with total IgE level more than 500 PRU/ml were analysed for determining the limits of IgG to A.f. concentrations. PMID- 1421314 TI - [Effects of alpha-interferon on the level of adenosine metabolism enzymes and bactericidal activity of macrophages in staphylococcal infection]. AB - In staphylococcal infection the changes in functional ability of macrophages occur: their oxygen-depending bactericidity and adenosine-desaminase activity are depressed 5-nucleotidase ability increases. Introduction of homologous alpha-IFN in the dose of 1 x 10(3) u/mouse leads to enhancing macrophage bactericidity of the animals infected, inhibits their 5-nucleotidase activity and enhances adenosine desaminase one. Influence of alpha-IFN on the activity of adenosine metabolism enzymes in macrophages can be considered one of the most important mechanisms of its modulating effect in bacterial infections. PMID- 1421315 TI - [Effects of modulators and cytostatics on catabolism of I-125 desoxyuridine in tumors (express-method of antineoplastic modulator screening)]. AB - El-4 and P-815 murine tumor cells labelled by 125I-deoxyuridine or 51Cr were administered in 7-day subcutaneous syngeneic tumors or subcutaneously. At the same time different groups of mice were treated by LPS plus MDP, beta-C7H15-MDP, dexal-MDP, polyacrylamide-MDP-phosphatidylethanolamine, adriblastin or cyclophosphamide. It was shown that cytostatics and immunomodulators significantly delayed catabolism and withdrawing of 125I-deoxyuridine (that has not been incorporated in DNA) from tumor cells. This delay was correlated with the inhibition of tumor nodes growth rate. It is concluded that influence of cytostatics and immunomodulators on catabolism and withdrawing rate of 125I deoxyuridine from tumor cells relates to their cytostatic effect and may be used at the earliest screening step of immunomodulator analysis. PMID- 1421316 TI - [Radiation protective properties of a synthetic antagonist of glucocorticoids RU 38486]. AB - Radioprotective properties of synthetic antiglucocorticoid RU 38,486 were investigated. It was demonstrated that this antagonist of glucocorticoids possesses radioprotective effect in vitro and in vivo systems. Radioprotective properties at molecular level exhibited in inhibition of postirradiation endonuclease activation and in prevention of internucleosome chromatin degradation. Involvement of cytosol glucocorticoid receptors in initiation of radiation-induced programmed cell death is discussed. PMID- 1421317 TI - [Effects of atrial natriuretic peptide AP II on the morphofunctional state of the adrenal cortex of white rats]. AB - The effect of atrial natriuretic peptides synthetic analog AP II on adrenal zona glomerulosa and zona fasciculata physiological regeneration have been studied on male rats. The 3H-thymidine incorporation into DNA in adrenal cortical cells was evaluated in 4 and 24 h after intraperitoneal injection of 10 or 100 mcg/kg AP II. Besides, we have investigated the influence of AP II on adrenal cortical cells karyometric parameter in 4 and 24 h and aldosterone plasma concentration in 1 h after injection. 10 mcg/kg AP II increased the fraction of labelled nuclei in zona glomerulosa and decreased the aldosterone plasma level. No significant changes were seen in zona fasciculata cells proliferation. 100 mcg/kg AP II inhibited the DNA synthesis process in adrenal zona fasciculata, but had no significant influence on zona glomerulosa physiological regeneration and aldosterone plasma concentration. No nuclear morphometric parameter changes were observed in adrenal glomerulosa and fasciculata cells of AP II--treated animals. PMID- 1421318 TI - [Seasonal and circadian fluctuations in blood biochemical indicators in mice in natural conditions and exposed to constant light]. AB - The fluctuations of activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and those of the levels of protein, glucose, cholesterol, bilirubin, creatinine, blood urea nitrogen, K+, Cl-, Na+ in blood plasma of mice in natural conditions (NC) and exposed to constant light (CL) were studied in different seasons of the year (in January, April, July, October) on days 18, 24, 6 (at 12 o'clock). Most indices both in NC and CL animals had seasonal rhythm similar for each of them. This proves a primary effect of environmental geoclimatic factors of formation of circadian periodicals as compared to desynchronization in constant light revealed by Kosinor analysis in winter (acrophase from 14.16 till 16.32 o'clock) and autumn (acrophase from 23.03 til 4.40 o'clock). During the same seasons one can observe the maximum desynchronization influences of constant light, which leads to abrupt falling (to the 10-fold and more) of the fluctuations amplitude and in some cases to stabilization of circadian rhythm. PMID- 1421319 TI - [Contribution of genetic constitution to the formation of circadian rhythm of several hemodynamic parameters]. PMID- 1421320 TI - [Neural regulatory effects on the contractility of heart ventricles]. AB - As a result of acute experiments on cats we revealed the approaches to choosing the best indices of the contractility of the left and the right cardiac ventricles in the concrete conditions of the experiment on the basis of the original criterion of optimality. For revealing neural inotropy influences we suggest the index based on the combined changes of optimum indices. A new approach to revealing reflex influences on contractility in the conditions of intact blood circulation is worked out, which is based on the comparison of these influences with the control changes of haemodynamic parameters. PMID- 1421321 TI - [Morphological aspects of broad-plasma lymphocyte migration through ependymal cell of mammalian vascular plexus]. AB - A morphological study of the cerebral vascular plexus was performed to find out the ways of blood cell migration from the vascular lumen into the liquor and in the opposite direction, as well as through ependymocytes. The material of the study consisted of cattle (cows and goats) with the body weight of 500 kg and 30 40 kg, respectively. From each animal species 16 animals were used in the study. Investigational methods included light and electron microscopy. Sequential stages of broad-plasma lymphocyte migration from the vascular lumen through endotheliocytes, capillary basal layer, connective tissue stroma, basal membrane of ependymocytes, as well as through proper ependymocytes have been revealed. The authors refer the phenomenon of broad-plasma lymphocyte migration to the phenomenon of emperipolesis. PMID- 1421322 TI - [Modular structure of the rat hypothalamus]. PMID- 1421323 TI - [Morphofunctional aspects of genetic analysis of osteogenesis imperfecta in cultured skin fibroblasts]. AB - Osteogenesis imperfecta (OI) is a disease with biochemical evidence of abnormality in collagen biosynthesis. We report here that expression of the OI phenotype extends to the level of dermal fibroblast morphology in vitro. Growth characteristics and morphology of control (n = 3) and 01 cell strains (n = 10) were compared. Our results show that (1) OI fibroblasts take longer time (16 days) than that with control cells (13 days) to reach stationary phase; (2) OI fibroblasts achieve a lower cell density (1.0 +/- 0.09) at stationary phase compared to control cells (1.47 +/- 0.1); p < 0.01; (3) cell shape (expressed as the width/length ratio) was also abnormal in OI cells: they have significantly increased ratios (p < 0.05) compared to control. These changes were associated with an increased level of fibronectin concentration and engorged cytoplasmic vesicles in dermal fibroblasts in vitro. We have reason to suspect that dysmorphology of fibroblasts may be related to aberrant collagen metabolism that leads to inadequacy of extracellular substratum, that in its turn hinders normal adhesion of cells as well as their spreading, morphology and fibronectin concentration. PMID- 1421324 TI - [Effects of different regimens of hyperbaric oxygenation on transcriptional activity and morphology of frontal cortex neurons in occlusion of the common carotid artery in rats]. AB - The effect of different regimens of hyperbaric oxygenation (HBO) on cortical pyramids morphology and transcription were studied under occlusion of common arteria carotis. The effect of early (3 hours after occlusion) and late (14 hours after occlusion) use of 1.2 and 2.0 ata of HBO was estimated. The rats were killed 15 minutes or 24 hours after HBO session. The effect of early use of HBO was normalizing, stabilizing and independent on the dose. Protecting effect of the late HBO on morphology and transcription activity of nuclear chromatin of pyramids was higher in the 1.2 ata regimen. In case of late HBO both pressures produced depressing effect on the nucleoplasmic chromatin, transcription. PMID- 1421325 TI - [A method of multivariate analysis of data in the study of the effects of space flight factors on the rat brain neuron structure]. AB - The usage of some methods of multivariate analysis for neuro-morphological studies is discussed. The alterations of dendritic trees of pyramidal neurons of layer III of visual cortex of the rat exposed to the influence of space flight aboard biosputnik "Cosmos-1887" were studied and the results are described to illustrate the methods power. o-technique of factor analysis was shown to be suitable for processing of the data obtained from an experiment with complex environmental conditions. PMID- 1421326 TI - [Is transferrin a neurotrophic factor controlling myosin composition of the skeletal muscle?]. AB - After transferrin injection to the slow m. soleus of guinea pig no immunohistochemical changes in myosin composition with monoclonal antibodies (AB) against fast myosin heavy chain (HCf) have been found. All muscles fibers in intact and experimental animals were identified as slow ones (type I of muscle fibers). After colchicine treatment of nerve trunk innervating slow muscle, some muscle fibers reacting with monoclonal AB against myosin HCf have been found. However, after colchicine treatment of nerve trunk and transferrin injection also some muscle fibers in slow muscle reacting with monoclonal AB against myosin HCf have been found. In appears that transferrin probably can not be the factor of neurotrophic control for myosin composition in skeletal muscle. PMID- 1421327 TI - [Activity of smooth muscle cells in experimental ileus under the effects of ultraviolet laser irradiation]. PMID- 1421329 TI - Looking through the crystal. PMID- 1421328 TI - [Effects of minced muscle tissue implantation and subsequent laser therapy on regeneration of skeletal muscles in guinea pigs]. AB - It is known that regenerative capacity of skeletal muscles in guinea pigs is less than in rats. The guinea pig muscle regenerates are characterized by smaller muscle fibers and greater amounts of interstitial connective tissue. The present experiments were designed to stimulate the regenerative capacity of muscle tissue in adult guinea pigs, using tissue and laser therapy. It was shown that the minced muscle tissue implantation to the site of injury in m. gastrocnemius increased the quantity of regenerating muscle tissue. When the same operation was combined with following laser therapy the increase of muscle tissue was observed as well but not by far. At the same time laser therapy promoted noticeable acceleration of fibrin resorption, wound healing and regenerative modifications in implanted muscle fragments. Thus, the present methods stimulated relatively law regenerative capacity of guinea pig muscle tissue and promoted more qualitative recovery of injured area. PMID- 1421330 TI - Health promotion in the British workplace: a suitable case for treatment? AB - Over the years, the British workplace has provided a fertile bed for the growth of health-related surveillance, research and intervention. A brief review of the literature on this topic, highlights the plethora of different groups involved, and their differing agenda in relation to the health of the workforce. Key participants, including the workforce, have different perceptions of, and commitment to, the promotion of health. Health promotion should be concerned with reducing inequalities in health experience and opportunity but, because the large majority of British workplaces have no access to appropriate occupational health services, most health promotion activity is concentrated in large profit-making concerns with suitable existing facilities. In this article, the background to health-related initiatives in the British workplace is given, and the various contributions to workplace health promoting activities are noted. Their potential for mis-use is discussed and the need for a more comprehensive and integrated approach to primary care, including health promotion, is suggested. In the present economic climate in Britain there is a need to create a comprehensive database of all health promotion activities so that, with collaboration, integration and coordination of all initiatives, regardless of venue, we can put our present meagre resources to best use. PMID- 1421331 TI - Tuberculosis screening in health service employees: who needs chest X-rays? AB - There is uncertainty in the NHS about which individuals should be offered pre employment screening by chest X-ray and whether this procedure is of value in the detection of tuberculosis. To provide evidence for practice, pre-employment chest X-ray and tuberculin skin test status were examined retrospectively for employees of a health district. Cases were those with an abnormal chest X-ray; referents were a sample of the remainder with a normal chest X-ray. The majority of the population had positive tuberculin skin tests and there was no difference between cases (58 positive out of 68) and referents (170 positive out of 212). Most of the X-ray abnormalities were trivial; four findings were thought significant, but would have caused no problems if undetected and none of these findings was related to tuberculosis. We conclude that in new employees in Hampstead health district, X-ray abnormalities are rare and not predicted by testing tuberculin skin reactivity; neither procedure is justified routinely as a means of screening for tuberculosis. The situation in districts with a high incidence of tuberculosis needs to be investigated. PMID- 1421332 TI - Investigation into the environmental factors associated with the incidence of skin disease following an outbreak of Miliaria rubra at a coal mine. AB - A retrospective study was undertaken to examine by interactive linear modeling a possible association between environmental conditions and the incidence of skin conditions (excluding athletes foot) in a coal mine following an increase in skin rashes, mainly 'prickly heat' (Miliaria rubra). An increase in the incidence was found with increasing surface temperature and underground air velocity; a decreased incidence with increased underground air quantity (air volume per unit time); whilst the relationship with underground temperature was found to be quadratic with incidence decreasing until 27 degrees C wet bulb (although this is not necessarily the optimum temperature for other purposes) and then increasing. The association between skin incidence and environmental factors was strongest (in terms of variance explained) when the incidence was associated with the environmental conditions of 4 to 8 weeks previously. The constant nature of relative humidity over the period prevented an examination of its relationship with rash incidence. Possible strategies for reducing the incidence of 'prickly heat' are discussed. PMID- 1421333 TI - Relationship between occupational health care and absenteeism. AB - A connection is generally assumed between occupational health care (in Dutch 'bedrijfsgezondheidszorg', or BGZ) and a reduction in absenteeism. In the Dutch literature various authors and researchers make great claims for the effect of occupational health care in reducing absenteeism. As yet, however, they have not concerned themselves very much with providing proof for the validity of their position. They speculate as to the positive influence of occupational health care on the health and welfare of employees and assume a direct connection between it and the reduction of absenteeism, but they do not have at their disposal empirical research results to support their speculations. So far as we know solid research of an experimental or quasi-experimental design into the relationship between occupational health care and absenteeism has never been carried out. Recently, however, an experiment with occupational health care for teaching personnel (in Dutch: Experiment met BGZ voor Onderwijspersoneel, or EBO) did take place, providing the opportunity to determine the influence of occupational health care on absenteeism in a quasi-experimental setting. Unfortunately, the results of the experiment indicate that the relationship between occupational health care and absenteeism is more complex than is generally assumed. In the course of the experiment, and in particular during the final year, the level of absence in the experimental group rose considerably, while in the control group it fell slightly. That rise was mainly due to the increase in the number of persons who were sick for a long period of time (at least 6 months). PMID- 1421334 TI - Effects of a change in shift work on health. AB - Aspects of health were studied in a sample of factory workers who changed their pattern of working from 'fortnight about' to three advancing shifts. Within the same factory and doing similar work there was a comparison group who were working permanent days only. The change in shifts was associated with more difficulty with sleep, more indigestion, higher alcohol consumption, reduced alertness and a worse social life. There was more minor psychiatric disturbance in those who worked three shifts than in those who worked days only. PMID- 1421335 TI - Impact of the new European legislation regarding vocational driving on London Transport Medical Service: the doctor's role. AB - The outcome of the first 1000 medical examinations undertaken by London Transport Medical Service (LTMS) to comply with the regulations for non-passenger carrying public carriage vehicle licence holders was analysed to assess where the primary role of the examining doctor affected the final outcome. It was found that the primary involvement of the doctor possibly altered the outcome in only two cases. In 49 cases, the medical practitioner had an interpretative role in the final assessment, or in the pursuit of further information, such as clarification of past history from other sources. In these cases, actual contact with the applicant did not affect the final outcome. PMID- 1421336 TI - Does diving damage your brain? PMID- 1421337 TI - Acoustic trauma in a telephone operator. AB - This case report describes an incident where a telephone operator suffered acoustic trauma from a subscriber blowing a whistle down a telephone mouthpiece, the sound being transmitted into the ear of the operator. Evidence of hearing loss persisted for several months before complete recovery was achieved. Comparison is made with hearing loss associated with the use of cordless telephones. PMID- 1421338 TI - Pre-employment colour vision testing. PMID- 1421339 TI - Pre-employment colour vision testing. PMID- 1421340 TI - Accidents in the workplace. PMID- 1421341 TI - Disaster and the occupational physician. PMID- 1421342 TI - Lung health: a global struggle. PMID- 1421343 TI - Skin testing with recombinant Mycobacterium intracellulare antigens. AB - The immunoreactivity of four recombinant Mycobacterium intracellulare beta galactosidase fusion proteins, which correspond to 22, 40, 43 and 85 kDa M. intracellulare antigens, was assessed. Lymphoproliferative assays demonstrated that Escherichia coli lysates containing each of the fusion proteins stimulated T cells in vitro. Purified preparations of three of these recombinant M. intracellulare antigens (22, 43 and 85 kDa) also induced delayed-type hypersensitivity (DTH) reactions in sensitized guinea pigs. However, the skin test responses evoked by each of these antigens was not species-specific. Given these results, the potential utility as skin test reagents of the purified antigens or peptides derived from these proteins is discussed. PMID- 1421344 TI - In vitro activity of meropenem and imipenem against mycobacteria: development of a daily antibiotic dosing schedule. AB - The activity of two carbapenem antibiotics, meropenem and imipenem, against Mycobacterium species was assessed by means of the Bactec 460 radiometric apparatus. This system allowed a result to be read in 4-10 days. The instability of imipenem, particularly, in the test system necessitated the development of a regimen of daily addition of antibiotic to permit a more accurate assessment of antibiotic activity to be made. When antibiotic-containing media are incubated for long periods, as is the case when determining antimycobacterial activity, the stability of test antibiotics is an important factor that must be considered. PMID- 1421345 TI - The humoral immune response after BCG vaccination: an immunoblotting study using two purified antigens. AB - The specific IgG response induced by BCG vaccination was investigated in 27 adults using two purified BCG antigens in a dot immunoblotting assay. The reflectance values increased significantly after vaccination when P64 but not when P32 was used as the antigen. The values measured after vaccination were compared with those obtained when testing sera from patients with tuberculosis. We observed that the level of anti-P64 IgG reached after BCG immunization was high enough to preclude a serological differential diagnosis with tuberculosis. PMID- 1421346 TI - Occurrence of mycobacteria in biofilm samples. AB - The occurrence of mycobacteria was studied in 50 biofilm samples from water treatment plants, domestic water supply systems and aquaria. Mycobacteria were found in 90% of the samples and their densities usually ranged between 10(3) and 10(4) cfu/cm2 (maximum density 5.6 x 10(6) cfu/cm2). Organic substances such as plastics and rubber were usually colonized by larger numbers of mycobacteria than inorganic substances such as copper and glass. The highest mycobacterial densities were found on plastic surfaces which were continuously perfused with water at temperatures between 22 and 30 degrees C. The species identified include Mycobacterium chelonae, M. flavescens, M. fortuitum, M. gordonae, M. kansasii, and M. terrae/nonchromogenicum. The occurrence in microcolonies indicate that biofilms may be an important replication site of aquatic mycobacteria. PMID- 1421348 TI - The impact of changing BCG coverage on tuberculosis incidence in Swedish-born children between 1969 and 1989. AB - In April 1975, the mass vaccination of newborns against tuberculosis was replaced by selective vaccination of groups at risk. BCG coverage fell from more than 95% before 1974 to 1.8% between 1975 and 1982 and thereafter reached an average of 13.7% up to 1989. The cumulative incidence of tuberculosis before 5 years of age was estimated among children born in Sweden during periods of high, low and moderate increasing BCG coverage. The incidence figures per 100,000 children was 0.8, 3.9 and 2.9, respectively, for children born to Swedish parents and 2.6, 39.4 and 13.2, respectively, for those born to foreign parents. The observed incidence of tuberculosis among non-BCG vaccinated children born to Swedish parents was within the expected limits given by a prognostic model based on the natural change of the risk of infection. The effectiveness of the selective BCG vaccination programme, which was intensified after 1981 for the second generation of immigrants, was estimated to 0.82 (95% confidence interval 0.38, 0.95) assuming that there was no change of the risk of infection for children born to foreign parents over the period studied. From April 1975 to December 1989, tuberculosis was notified in 85 children born in Sweden during the same period, 7 of them were BCG vaccinated and 78 non-vaccinated, 45 were symptomatic, 3 of them with disseminated tuberculosis. PMID- 1421347 TI - Proposal of an improved score method for the diagnosis of pulmonary tuberculosis in childhood in developing countries. AB - 210 children aged less than 5 years, referred to the Arua Regional TB Centre (Uganda) for suspected pulmonary tuberculosis (PTB), were examined by anamnesis, clinical examination, Mantoux test, gastric washing, chest X-ray. The response to treatment criterion was applied to the patients treated. According to the score method suggested by Ghidey and Habte, 31 children were diagnosed as PTB patients. 30 of the 31 children with PTB tested positive for alcohol acid-fast bacilli (AAFB) in the aspirated juice. The Mantoux test and X-rays gave a minor contribution to diagnosis. The clinical results are commented. A statistical analysis was carried out to evaluate the role of gastric washing in the diagnosis of PTB in children under 5 years of age (sensitivity, 96.8%; specificity, 92.2%; positive predictive value, 68.2%; negative predictive value, 99.4%). The response to treatment was also evaluated. A modified enlarged score method (based on gastric washing and including response to treatment) is proposed to be applied in developing countries where chest X-ray and other facilities are often lacking. PMID- 1421349 TI - Tuberculosis control programme in Beijing. AB - Since 1978 a new tuberculosis control programme based on modern concepts has been started in Beijing. The main goals of the programme were: (1) To prioritize the control of sources of infection; (2) to instigate fully supervised treatment (FST) for new smear-positive patients; (3) to extend services to the rural areas. A four-level network of tuberculosis control services has been organized both in urban and rural areas. Tuberculosis control has been integrated into rural primary health care. Coverage of FST among new smear-positive cases increased to 93% in 1990. A standard regimen, 1HS/11H2S2 has been used for initial treatment. A reserve regimen of RFP and EMB was added to those who failed to convert in 6 months. Since 1988 a 6-month intermittent short-course regimen has been introduced as standard regimen. Case-finding has been intensified since 1980 through symptomatics. Control of chronic excreters was achieved through FST of new smear-positive cases and fully supervised retreatment of old chronic cases. The new tuberculosis control programme has proved highly successful in controlling sources of infection. The prevalence of smear-positive pulmonary tuberculosis in Beijing during the national surveys in 1979, 1984-1985 and 1990 was 127, 56 and 16 per 100,000 respectively. The average annual reduction rate was 17%. This successful experiment has been recognized as a model for the whole country. PMID- 1421350 TI - Early diagnosis of tuberculosis by fibreoptic bronchoscopy. AB - We carried out a retrospective study of the methods used to achieve an early diagnosis of 67 patients with pulmonary tuberculosis treated at our institute between 1984 and 1989. Sputum bacteriology was positive in 56 of the 67 patients, 22 were positive on microscopical examination of smears and on culture and 34 on culture alone. The 11 patients with negative sputum bacteriology were all diagnosed by fibreoptic bronchoscopy. In addition, 21 of the 34 smear negative/culture-positive patients were examined by fibreoptic bronchoscopy and the initial diagnosis was made in 7 of these. Thus the initial diagnosis was made by sputum bacteriology in 49 cases and by fibreoptic bronchoscopy in 18 cases. The median number of days between obtaining a specimen and starting therapy was 7 days for sputum microscopy, 41 days for sputum culture, 7 days for microscopic examination of bronchoscopy specimens, 51 days for culture of the same and 19 days for biopsy. Fibreoptic bronchoscopy is therefore useful for the diagnosis of cases of tuberculosis in which tubercle bacilli are not detected in sputum and, in some instances, for an earlier diagnosis of smear-negative/culture-positive patients. PMID- 1421351 TI - Defaults, defaulter action and retrieval of patients during studies on tuberculous meningitis in children. AB - Chemotherapy studies were undertaken on 180 children, aged between 1 and 12 years, with tuberculous meningitis. They received therapy for 12 months. As approximately one-half of the patients came from outside Madras city, retrieval action was not possible in all cases of default. Despite this, a high rate of compliance and punctuality was achieved as a result of initial and periodic motivation. This report highlights the role and importance of motivation in the prevention of default and the retrieval of defaulters during the treatment of children with tuberculous meningitis. PMID- 1421352 TI - An unusual presentation of oesophageal tuberculosis. AB - Oesophageal tuberculosis secondary to tuberculous mediastinal lymphadenopathy is a very unusual presentation of adult tuberculosis. We report a young patient who presented with anorexia and weight loss. The chest radiograph and CT scan revealed mediastinal lymphadenopathy causing extrinsic oesophageal compression on the barium swallow. This was confirmed by upper gastrointestinal endoscopy. Four weeks later, because of spontaneous partial relief in dysphagia, upper gastrointestinal endoscopy was repeated and revealed an ulcerated lesion with nodular margins at the mid-oesophagus. Biopsy from the ulcer margin revealed non caseating granulomas. The patient had complete relief of dysphagia and other symptoms within 3 weeks of start of antituberculosis therapy. PMID- 1421353 TI - The medical treatment of a tuberculous tracheo-oesophageal fistula. AB - Tracheo-oesophageal (TE) fistulas caused by Mycobacterium tuberculosis are rare and usually require both surgical treatment and medical treatment with antituberculosis drugs. A patient with a tuberculous TE fistula and mediastinal lymphadenitis was successfully treated by medical management alone. PMID- 1421354 TI - Clinical evaluation of 99mTc-MIBI myocardial tomography for detecting coronary artery disease. AB - To evaluate the clinical efficacy of 99mTc-MIBI myocardial tomography for detecting coronary artery disease, 34 consecutive patients who underwent both 99mTc-MIBI study and coronary arteriography were included in the present study. Ten without and 24 with significant coronary artery disease were documented by coronary arteriography. The overall sensitivity and specificity of 99mTc-MIBI study for detecting coronary artery disease were 91.8% (22/24) and 80.0% (8/10), respectively. In subset studies, 16 of 17 (94.1%) patients with previous myocardial infarction and 6 of 7 (85.7%) patients with significant CAD but without MI were identified as abnormal. Reversible perfusion abnormalities were shown in 4 of 5 patients undergoing both exercise and rest studies. Rest perfusion abnormalities were shown in 2 patients with unstable angina pectoris who underwent only rest study. In conclusion, 99mTc-MIBI myocardial tomography provides a reliable method for detecting coronary artery disease. Rest study has high sensitivity for identifying patients with MI, and exercise/rest study can identify patients with significant CAD but without MI. PMID- 1421355 TI - Growth inhibition and differentiation of promyelocytic cells (HL-60) induced by BC-4, an active principle from Boswellia carterii Birdw. AB - The induction of cell differentiation and growth inhibition of HL-60 cells by Bc 4, an active principle from Boswellia carterii, was studied in vitro and in vivo. The proliferation of HL-60 cells was found to be inhibited by Bc-4 at a concentration of 5-10 micrograms/ml. Under the action of Bc-4, the acid phosphatase and NBT reduction activities in HL-60 cells were increased, and phagocytosis of cells was also induced. All these activities were concentration dependent. The HL-60 cells were induced by Bc-4 to differentiate into more mature cells morphologically. The in vivo growth of HL-60 cells in mouse subrenal capsules (SRC) and in diffusion chambers inoculated into mice was inhibited by Bc 4 at a dose of 50 mg/kg. The morphology of HL-60 cells treated by Bc-4 in diffusion chambers exhibited characteristics of mature granulocytic cells. PMID- 1421356 TI - The use of an external tibial fixator in the treatment of genu varum. AB - This paper reports 72 cases of genu varum treated by a U-shaped osteotomy of the tibia and an oblique osteotomy of the fibula in combination with immobilization effected by a specially designed external tibial fixator. Owing to this modified approach, the patients were able to stand up and move about much earlier than usual. Our trial yielded 80.7% excellent, 16.6% good and 2.7% fair results. The treatment course was shortened to two thirds of the time required when using previously described techniques. PMID- 1421357 TI - The application of Dick instrumentation in spine surgery. AB - From June, 1989 to March, 1991, 24 cases with various spinal disorders were treated in our department using the Dick technique. The results were as follows: In the fresh fracture group (7 cases), all the spine fractures were reduced anatomically: the 2 cases without neurological defects returned to work 3 months after operation; the 3 cases with incomplete paraplegia had rapid neurological recovery; and the 2 cases with complete paraplegia showed no recovery after operation. In the late fracture group (10 cases), traumatic kyphotic curves were partially reduced and back pain was decreased markedly in all: Muscle power was increased significantly in 3 cases; spasticity was remarkably improved in 2 cases; 3 cases obtained complete cure of incontinence; and 4 cases had no significant improvement. In 3 cases with ankylosing spondylitis, the initial average kyphotic curve was 73.3 degrees, while the postoperative average curve was 28.3 degrees. The result of treatment of spinal stenosis due to degenerative spondylolisthesis (1 case) was good; slipping vertebrae were stabilized and fused with the Dick system after thorough decompression. In 1 tumor and 2 Tb-spine cases, the patients recovered and were ambulatory soon after operation. PMID- 1421358 TI - The quantitative alteration of 5s rRNA during the development of mammalian erythroid cells and its effect on DNA synthesis in SP2/0 mouse myeloma cells. AB - Mouse myeloma cells (SP2/0) were incubated with 125I-5s rRNA from rabbit reticulocytes and processed for autoradiography. The results indicated that 5s rRNA could pass into the nuclei of mouse myeloma cells. In a separate experiment, SP2/0 were incubated with cold 5s rRNA, then with 3H-TdR and processed for autoradiography. It was found that in the mouse myeloma cells, DNA synthesis and cell division were obviously suppressed. In another series of experiments, rRNA was extracted from rabbit bone marrow, reticulocytes and erythroid cells and from rat embryonic liver and erythroid cells. The rRNA was analyzed by agarose electrophoresis. It was found that the amount of 5s rRNA in various stages of erythroid development changed along with the denucleating process. Thus it seems likely that 5s rRNA from mammalian erythroid cells could play a role in reversing the malignant phenotype of tumor cells and denucleation of mammalian erythroid cells through inhibiting DNA synthesis. PMID- 1421359 TI - Molecular cytogenetic study of short arm aberrations in human D, G group chromosomes. AB - Six cases of Dp+/Gp+, 10 cases of D/G translocation, 1 case of supernumerary marker chromosome, and 1 case of Yqs were studied using molecular and cytogenetic techniques. The Ag-NOR frequencies of the Dp+ and Gp+ groups were found to be higher than those of normal controls, while their satellite association frequencies were lower. Autoradiographic silver grains were not significantly distributed along the p+ part of the marker chromosome as revealed by chromosomal in situ hybridization using an rRNA probe. This result differs from our previous report. It is suggested that there might be different mechanisms for the formation of p+ on acrocentric chromosomes. D/G translocation cases were found to have lost their NOR. A study of supernumerary marker chromosomes and Yqs cases suggested that the marker chromosome and Yqs exerted no phenotypic effect. The mechanism of their formation is discussed. PMID- 1421360 TI - The relationship between the changes in plasma atrial natriuretic peptide and renin angiotensin contents and hemodynamics in pulmonary hypertensive rats. AB - Pulmonary artery pressure (PAP) increased significantly in rats after hypobaric hypoxic exposure for 15 days (CH15) (P less than 0.001) and was maintained at the same level after prolonged hypoxic exposure for 40 days (CH40). There were no significant changes in carotid systolic and diastolic blood pressure in CH15 and CH40 rats. The contractility of the right and left ventricles of CH15 and CH40 rats showed no difference as compared with the control group. Plasma atrial natriuretic peptide (ANP) content in CH40 rats was obviously increased (P less than 0.001), while angiotensin II (AII) dropped markedly (P less than 0.05). Plasma renin activity was increased in both hypoxic groups (P less than 0.05 respectively). These results indicate that during chronic hypoxia, plasma ANP and the renin-angiotensin system (RAS) play an important role in the modulation of pulmonary as well as systemic hemodynamics. They may work cooperatively to limit the development of pulmonary hypertension and to maintain systemic blood pressure within the normal range. PMID- 1421361 TI - STD epidemiologic analysis at national surveillance spots in the period 1987 1990. AB - This article summarizes surveillance data of STDs at 16 urban monitoring centers in 1987-1990. During the four year period, 125,493 STD cases were reported. The average annual incidence was 77.80/100,000. Because the rate of increase in females (65.85% per year) was greater than that in males (36.81% per year), the male-to-female ratio fell from 2.39:1 (1987) to 1.34:1 (1990). The number of STD cases reported from all centers tended to increase, and the overall rate of increase was 46.61% per year. The major disease was gonorrhea, with a constituent ratio of 59.22% (1990). However, condyloma acuminatum and nongonococcal urethritis had greater rates of increase (105.03% and 85.14% per year, respectively). The 20-39 year age group accounted for 82.10% of total cases, for STD patients were mostly in the sexually active population. The STD incidence among self-employed businessmen (1206.06/100,000, in 1990) was highest among professional populations. According to analysis of different regions, STD incidence was highest in the southern cities (203.00/100,000, 1990). The greatest rate of increase of STDs was in Yangtze River Valley cities, where the average annual rate of increase was 71.41%. PMID- 1421362 TI - Breast volume measurement in 125 young Chinese women. AB - The authors carried out research on breast volume and body surface anatomy of 125 unmarried young women. As a result, an average breast volume for young Chinese women was obtained (325.36 +/- 12.66 ml), and a table together with several linear equations for calculating breast volume were derived. These will provide plastic surgeons with useful tools for designing mammaplasty procedures. PMID- 1421363 TI - A comparative study of the outcome of renal transplantation in peritoneal dialysis and hemodialysis patients. AB - Fifty-four cases of renal transplantation performed in peritoneal dialysis (PD) patients were compared with 48 cases in hemodialysis (HD) patients. Three immunosuppressive treatments were used: prednisolone, azathioprine and cyclosporine. Methylprednisolone was used to treat rejection, and polyclonal Atgem or monoclonal OKT3 antibodies were used if there was no response. There was no difference in sex, age, donor source, immunosuppressive regime, duration of dialysis before transplantation, or duration of follow-up between the two groups. Following transplantation, there was no significant difference in patient mortality and survival or graft survival between the groups. The incidences of infections were also similar in the two groups. PD is commonly used in developing countries as an alternative to hemodialysis for the treatment of chronic renal failure. This study has shown that renal transplantation can be successfully performed in patients treated by this method. PMID- 1421364 TI - Comparative study of 99mTc-HM-PAO SPECT brain imaging, EEG and CT scanning in epileptic patients during the interictal period. AB - Forty patients with epilepsy in the interictal period were studied with 99mTc (HM PAO) SPECT brain imaging, EEG and CT scanning. Four cases of generalized epilepsy had normal findings on EEG, SPECT imaging and CT scanning. Two cases of childhood benign partial seizures had abnormal EEG, but the SPECT brain imagings were normal. Regional hypoperfusions of various extents were found in 20 of the 34 patients with complex partial seizures. Among the 34 patients, 17 had abnormal EEG and 8 had abnormal CT scans. A good topographic concordance between regional HM-PAO hypofixation and EEG foci was found (39.1%). Localization of the lesion by SPECT imaging and CT scan was coincident in 5 cases (27.8%). The correlation between these three examination methods is discussed. PMID- 1421365 TI - Studies on intrahepatic cholelithiasis in west China. AB - Intrahepatic cholelithiasis is widespread in Asia and brings much suffering to the Chinese people. This paper presents a brief sketch of our clinical observations, research and some related views. PMID- 1421366 TI - Skin test inhibition by astemizole. AB - For the purpose of evaluating the therapeutic effect of antihistamines, we have set up an assay method called the "Skin Test Inhibition Index" (STII). Twenty subjects with hay fever were given astemizole (10 mg/d) for 7 days. Skin titration tests were carried out before and after treatment. Significant inhibition of the skin test reaction by astemizole was demonstrated (STII = 91). Another group of 6 hay fever patients was given astemizole (10 mg/d) for 10 days, and STII was determined on days 5 and 10 and on days 7, 14 and 21 after treatment. STII were calculated as 12, 108, 90, 10 and 7, respectively. These results demonstrate that astemizole is a long-acting antihistamine. PMID- 1421367 TI - Hepatocyte growth factor is a synergistic factor for the growth of hematopoietic progenitor cells. AB - Bone marrow (BM) stromal cells, which include macrophages, fibroblasts, endothelial cells, and adipocytes, have been shown to produce several factors that modulate the growth of BM progenitors. Hepatocyte growth factor (HGF) is a fibroblast-derived factor and has recently been shown to be a ligand for the c met proto-oncogene, a member of the receptor class of tyrosine kinases. c-met messenger RNA (mRNA) is predominantly expressed in epithelial cells, but has been detected in several murine hematopoietic progenitor cell lines, suggesting that HGF and met might function during hematopoiesis. Here, BM cells were found to express both met mRNA and protein. Moreover, HGF was shown to synergize with interleukin-3 and granulocyte-macrophage colony-stimulating factor to stimulate colony formation of hematopoietic progenitor cells in vitro. These results show that, in addition to its activity on epithelial cells, HGF is a new member of the functionally related group of factors that modulate hematopoiesis. PMID- 1421368 TI - Recombinant human tissue plasminogen activator for the treatment of established severe venocclusive disease of the liver after bone marrow transplantation. AB - Seven patients were treated with recombinant human tissue plasminogen activator (tPA) for severe hepatic venocclusive disease (VOD) that developed after bone marrow transplantation for hematologic malignancy. Recombinant human tPA (10 mg/d x 2 days) and heparin (1,000 U bolus followed by continuous intravenous infusion of 150 U/kg/d x 10 days) were begun a median of 9 days (range, 4 to 18 days) posttransplant. The median total serum bilirubin and percent weight gain from baseline were 19.4 mg/dL (range, 14.6 to 34.9 mg/dL) and 9.1% (range, 1% to 18.5%), respectively, at the start of tPA administration. Five patients responded to therapy with prompt reduction in total serum bilirubin within 96 hours of starting tPA. Three patients are alive 178 to 379 days posttransplant without evidence of VOD. No patient had significant hemorrhagic complications with tPA. We conclude that recombinant human tPA can be administered to patients with severe VOD at the dosage described. Whereas preliminary data suggests that recombinant human tPA can alter the natural history of severe VOD, further study is necessary to determine its efficacy. PMID- 1421369 TI - Clinical and cytogenetic responses to granulocyte-macrophage colony-stimulating factor in therapy-related myelodysplasia. AB - We treated 10 patients with a therapy-related myelodysplastic syndrome with escalating doses of granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) in a phase II trial and used sequential cytogenetic analyses to determine whether there was stimulation of nonclonal hematopoiesis. The GM-CSF was administered by continuous intravenous infusion over 2 hours daily for 14 days, followed by a 14-day rest period. The initial starting dose was 60 micrograms/m2/d. The GM-CSF dose was escalated within individual patients to 125 micrograms/m2, 250 micrograms/m2, and then 500 micrograms/m2/d until the peripheral blood neutrophil count at least doubled and exceeded 1,000/microL. GM CSF treatment then continued in monthly maintenance cycles. During 57 treatment courses, the neutrophil count increased in 52 but only doubled and exceeded 1,000/microL in 21. Mild eosinophilia was stimulated in five patients, but only two had greater than 1,000 eosinophils/microL. In only three patients was any stimulation of platelet or red blood cell production observed, and thus, little change in transfusion requirements occurred. The bone marrow karyotypes from individual patients either remained completely abnormal or became increasingly abnormal over the course of treatment. We found no evidence that GM-CSF preferentially stimulated normal marrow stem cells to proliferate or had the ability to eradicate the cytogenetically abnormal clone by inducing terminal differentiation. Although the effect on granulopoiesis was transient and dependent on continued GM-CSF treatment, the increase in the neutrophil count was clinically important in some patients, allowing more effective control of ongoing infections. PMID- 1421370 TI - Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group. AB - In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM 81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL-BFM-86 (minimal follow-up, 25 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM 81, the CNS was the most frequent site of failure. In ALL-BFM-83, there were no isolated CNS relapses, but more bone marrow (BM) relapses occurred. In ALL-BFM-86, localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients. PMID- 1421371 TI - Differential effects of sequential, simultaneous, and single agent interleukin-3 and granulocyte-macrophage colony-stimulating factor on megakaryocyte maturation and platelet response in primates. AB - Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) following interleukin-3 (IL-3) priming has been shown to increase thrombopoiesis. To elucidate the comparative abilities of IL-3 and GM-CSF in influencing megakaryocyte development in vivo, serial bone marrow analyses were performed on rhesus monkeys treated with 5 micrograms/kg/d of IL-3 and 5 micrograms/kg/d of GM CSF sequentially for 4 days each, simultaneously for 8 days, and as single agents for 8 days. Platelet counts maximally increased to a mean of 7.5 x 10(5)/microL (n = 3) on days 11 through 12 in monkeys treated with sequential IL-3/GM-CSF. In contrast, neither IL-3 alone nor simultaneously administered IL-3/GM-CSF elicited increases in thrombopoiesis between days 3 and 15. GM-CSF elicited a variable platelet response. Megakaryocyte ploidy distributions were significantly (P < .001) shifted between days 7 and 10 in monkeys treated sequentially and between days 3 and 15 in monkeys treated with combined IL-3/GM-CSF and with GM-CSF alone but not in monkeys treated with IL-3 alone. The changes in mean DNA content and megakaryocyte size, as determined by digital image analysis, were larger in monkeys treated with sequential IL-3/GM-CSF and with GM-CSF alone than in simultaneously treated monkeys. In addition, sequentially but not simultaneously treated monkeys showed increased numbers of megakaryocytes on bone marrow biopsy. We conclude that administration of IL-3 followed by GM-CSF treatment increases thrombopoiesis by sequentially increasing megakaryocyte numbers and maturation and that these effects are diminished by simultaneous administration of the two cytokines. PMID- 1421373 TI - Roles of erythropoietin, insulin-like growth factor 1, and unidentified serum factors in promoting maturation of purified murine erythroid colony-forming units. AB - We have used 75% to 90% pure murine erythroid colony-forming units (CFU-E) to delineate the processes and factors underlying their maturation. These CFU-E form 32 cell colonies and are drawn from what we term generation I of a six-generation long maturation sequence (Landschulz et al, Blood 79:2749, 1992). Applying assays of 59Fe-heme biosynthesis and colony numbers as measures of maturation and analyses of DNA degradation as an index of programmed cell death, we find that (1) erythropoietin (Epo) enhances maturation throughout most of its course; (2) Epo first seems able to forestall DNA degradation when CFU-E reach generation II; (3) the processes that Epo elicits thereafter start to persist when Epo is withdrawn; (4) insulin-like growth factor I (IGF-I) also forestalls DNA breakdown, but later loses effectiveness; (5) IGF-I adds little to maturation when Epo levels are high, but when Epo levels are low, enhances it substantially; and (6) for maturation to be entirely optimal, an unidentified serum factor(s) is probably required when Epo levels are high and is certainly needed when Epo levels are like those in normal animals. Quantitatively, about 40% of optimal in vitro erythropoiesis at normal Epo levels depends on Epo alone, another 30% or less on the addition of IGF-I, and the remaining 30% or more on the addition of unidentified serum factor(s). Applied together, these three or more factors lead to two-thirds of the maximum maturation realized with saturating Epo levels. Because we also find that heme accumulated in CFU-E culture can closely approach levels in red blood cells, we suppose that our conclusions apply as well to CFU-E maturation in vivo. PMID- 1421372 TI - Bryostatin 1 modulates the proliferation and lineage commitment of human myeloid progenitor cells exposed to recombinant interleukin-3 and recombinant granulocyte macrophage colony-stimulating factor. AB - The activity of protein kinase C (PK-C) has been implicated in the regulation of the growth and differentiation of both normal and neoplastic hematopoietic cells. We have examined the effects of the PK-C-activating agents phorbol 12,13 dibutyrate (PDBu), mezerein, and bryostatin 1 on the proliferation and lineage commitment of CD34+ human myeloid progenitor cells stimulated by recombinant interleukin-3 (rIL-3) and/or recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF). Although each of the PK-C activators administered alone induced no colony formation, coadministration of these agents with plateau concentrations of each cytokine (eg, 50 ng/mL) increased the number of day 14 granulocyte-macrophage colony-forming units by 100% to 150%. The number of pure and mixed neutrophil and macrophage colonies was substantially enhanced in the presence of PK-C activators, whereas the percentage and, in most cases, the absolute number of eosinophilic colonies was significantly reduced. The inhibition of eosinophilic colony formation was not overcome by the addition of rIL-5. Although addition of bryostatin 1 24 hours before rIL-3 abrogated the increase in total colony formation observed with simultaneous administration of factors, the inhibition of eosinophilic colonies and the increase in neutrophil/macrophage colonies persisted under these conditions. The addition of bryostatin 1 for up to 144 hours after rIL-3 continued to potentiate total colony formation, whereas the inhibition of eosinophilic commitment was lost after 120 hours. Together, these results suggest that pharmacologic interventions at the level of PK-C may regulate both the proliferation as well as the lineage commitment of human hematopoietic progenitors exposed to rGM-CSF and rIL-3. PMID- 1421374 TI - Release of interleukin-1 and interleukin-6 from human monocytes by antithymocyte globulin: requirement for de novo synthesis. AB - Antithymocyte globulin (ATG) is an effective treatment in patients with severe aplastic anemia (SAA). Its mechanism of action remains unclear, although it has been assumed to be immunosuppressive. However, ATG has also been shown by several laboratories to be immunostimulatory. Recently, interleukin-1 (IL-1) production has been found to be decreased in lipopolysaccharide-stimulated peripheral blood monocytes obtained from SAA patients. We have investigated the ability of ATG to function as an immunostimulatory agent via the production of IL-1 and IL-6 by normal human monocytes in vitro. Supernatants from ATG-stimulated monocytes were assayed for biologically active and immunoreactive IL-1 and IL-6. We have found that ATG, via its F(ab')2 fragment is a powerful inducer of IL-1 and IL-6 production. Furthermore, ATG induction of both cytokines from normal monocytes required de novo synthesis, as determined by 35S-methionine incorporation. Because these two cytokines synergize with other cytokines at both the stem cell and progenitor levels, these stimulatory properties of ATG may be relevant to the treatment of SAA. This would favor the hypothesis of a bimodal mechanism for ATG as an inducer of hematopoietic growth factors and as an immunosuppressive agent. PMID- 1421375 TI - Involvement of nuclear factor-kappa B in induction of the interleukin-6 gene by leukemia inhibitory factor. AB - Recent studies have indicated that the leukemia inhibitory factor (LIF) induces secretion of interleukin-6 (IL-6) in myeloid cells. We here show that synthesis of IL-6 by human mononuclear phagocytes exposed to recombinant human (rh) LIF is preceded by an increase of IL-6 transcript levels as a result of transcriptional activation of the IL-6 gene. Analysis of deleted fragments of the IL-6 promoter indicated that transcriptional activation of the IL-6 promoter was associated with enhanced binding activity of the transcription factor nuclear factor (NF) kappa B. Binding of activation protein (AP)-1 and NF-IL-6, also known to transcriptionally activate the IL-6 promoter, was not inducible by LIF. Furthermore, introduction of the NF-kappa B sequence into a heterologous promoter construct, but not of AP-1- and NF-IL-6-binding sequences, conferred inducibility by LIF to this promoter. Deletion of the NF-kappa B binding site in the IL-6 promoter was associated with loss of inducibility by LIF, lending further support for the notion that the NF-kappa B binding site is crucial for LIF-mediated induction of the IL-6 promoter. Taken together, our results show that rhLIF induces IL-6 gene expression in mononuclear phagocytes through transcriptional gene activation involving NF-kappa B. PMID- 1421376 TI - Isolation of a cDNA clone encoding a zinc finger protein highly expressed in T leukemia lines. AB - A cDNA clone encoding a novel zinc finger protein expressed in lymphoid cells has been isolated. This protein contains 5 repeats of the C2H2 motif previously described in the Drosophila gap gene, Kruppel, which is involved in embryo segmentation. Northern blot analysis showed that the messenger RNA (mRNA) encoding this protein is expressed at high levels in a variety of T-leukemia cell lines, at lower levels in some B cells, but is not observed in nonlymphoid cells. Within the T lineage, the mRNA is found at high levels in both alpha beta and gamma delta T cells. These data suggest that this cDNA, designated Hkr-T1, represents a gene that may contribute to the determination of the differentiation and the specificity within lymphoid cells. PMID- 1421377 TI - Alteration of the proliferative rate of acute myelogenous leukemia cells in vivo in patients. AB - Ten patients with active acute myelogenous leukemia (AML) received either 13 cis retinoic acid (RA) + alpha interferon (IFN) or recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) for 3 days. Cell cycle measurements were performed before and at the conclusion of administration of the bioactive agent(s). The proliferative rate of the leukemia cells in vivo decreased in four of five patients receiving RA+IFN whereas in one patient proliferation accelerated. The proliferative rate of AML cells accelerated in three of the five patients who received rhGM-CSF and slowed in two patients. These data show that while the proliferative rate of AML cells can be altered in vivo, the effect produced by bioactive agents may be the opposite of the desired effect. Furthermore, the studies described here demonstrate the usefulness of marrow biopsies for measuring the percent S-phase cells and the importance of measuring the duration of S phase so that the effects of bioactive agents on the cell cycle time of the leukemia cells can be determined. PMID- 1421379 TI - Compound heterozygosity in a complete erythrocyte bisphosphoglycerate mutase deficiency. AB - Erythrocyte bisphosphoglycerate mutase (BPGM) deficiency is a rare disease associated with a decrease in 2,3-diphosphoglycerate concentration. A complete BPGM deficiency was described in 1978 by Rosa et al (J Clin Invest 62:907, 1978) and was shown to be associated with 30% to 50% of an inactive enzyme detectable by specific antibodies and resulting from an 89 Arg-->Cys substitution. The propositus' three sisters exhibited the same phenotype, while his two children had an intermediate phenotype. Samples from the family were examined using polymerase chain reaction and allele-specific oligonucleotide hybridization and sequencing techniques. Amplification of erythrocyte total RNA from the propositus' sister around the 89 mutation indicated the presence of two forms of messenger RNAs, a major form with the 89 Arg-->Cys mutation and a minor form with a normal sequence. Sequence studies of the propositus' DNA samples indicated heterozygosity at locus 89 and another heterozygosity with the deletion of nucleotide C 205 or C 206. Therefore, the total BPGM deficiency results from a genetic compound with one allele coding for an inactive enzyme (mutation BPGM Creteil I) and the other bearing a frameshift mutation (mutation BPGM Creteil II). Examination of the propositus' two children indicated that they both inherited the BPGM Creteil I mutation. PMID- 1421378 TI - Hexamethylene bisacetamide in myelodysplastic syndrome and acute myelogenous leukemia: a phase II clinical trial with a differentiation-inducing agent. AB - Hexamethylene bisacetamide (HMBA) is a potent inducer of differentiation of a number of transformed cell lines in vitro. We report results of a phase II clinical trial in 41 patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) to whom HMBA was administered by continuous infusion for 10 days and repeated after an interval of 18 to 75 days. HMBA induced a complete remission (CR) in three patients and a partial remission (PR) in six patients. The median duration of CR was 6.8 months (range 1.3 to 16 months) and 3.7 months for PR (range 1 to 7 months). No significant difference was observed between responders and nonresponders with respect to the mean HMBA plasma levels, which were 0.86 +/- 0.04 mmol/L and 0.87 +/- 0.12 mmol/L, respectively. In certain patients morphologic and chromosome analyses provided evidence that HMBA induced differentiation of transformed hematopoietic precursors. The most prominent toxicity was thrombocytopenia, generally reversible on cessation of administration of HMBA. PMID- 1421380 TI - Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation. AB - The influence of intestinal bacterial decontamination on the occurrence of grades II to IV acute graft-versus-host disease (GVHD) was retrospectively analyzed in 194 predominantly adult patients treated by genotypically identical sibling marrow transplantation under conditions of strict protective isolation and intestinal antimicrobial decontamination. Forty-five patients (23%) developed acute GVHD and univariate analysis identified four features that significantly increased the risk for this reaction: chronic myeloid leukemia as the underlying disease, as compared with all other disease categories (P < .0001); female marrow donors for male recipients, as compared with other gender combinations (P < .005); ineffective, as compared with sustained growth suppression of intestinal anaerobic bacteria (P < .006); and methotrexate as the sole immunoprophylactic compound, as compared with cyclosporine containing regimens (P < .05). Using the duration of anaerobic growth suppression as a time-dependent explanatory variable, proportional hazards regression analysis confirmed these features as independent predictors for acute GVHD with relative risk estimates of 1.9 (95% confidence interval [CI], 1.3 to 2.7) for the immunoprophylactic regimen (P < .0004), of 1.8 (95% CI, 1.3 to 2.5) for the underlying disease (P < .0005), of 1.7 (95% CI, 1.2 to 2.5) for anaerobic decontamination (P < .002), and of 1.3 (95% CI, 1.1 to 1.6) for the donor/recipient gender combination (P < .008), respectively. Best subset selection modeling also identified the quality of anaerobic decontamination as the third most important predictor for acute GVHD, when all four significant features were included. Estimates of acute GVHD stratified by the quality of anaerobic bacterial growth suppression showed a strong influence of anaerobic decontamination in patients burdened by at least one of the other unfavorable factors (P < .009). In conclusion, this study provides strong evidence that sustained growth suppression of intestinal anaerobic bacteria after clinical sibling marrow transplantation can independently modulate the occurrence of grades II to IV acute GVHD, which is in concordance with previous results from animal transplantation models. Antimicrobial chemotherapy specifically targeted to the intestinal anaerobic bacterial microflora may be complementarily useful in preventing acute GVHD and should be investigated in a prospective trial. PMID- 1421381 TI - Impaired erythropoietin response to anemia after bone marrow transplantation. AB - Delayed erythroid recovery is common after bone marrow transplantation (BMT), with some patients continuing to require red blood cell (RBC) transfusion support for as long as 1 year. While the etiology is multifactorial, inadequate stimulation of erythroid progenitors by the erythroid growth factor, erythropoietin, may play a role. In this study, the erythropoietin response to anemia of 70 consecutive patients undergoing BMT at the Johns Hopkins Oncology Center was compared with the erythropoietin response in uncomplicated iron deficiency anemia. Erythropoietin levels were elevated for the degree of anemia early after BMT; however, at the time of marrow recovery, erythropoietin levels were significantly suppressed in both allogeneic and autologous BMT patients compared with the iron-deficient patients. Patients with acute graft-versus-host disease (GVHD) had a more marked suppression of the erythropoietin response to anemia. In the patients who remained anemic for extended periods of time (up to 12 months after BMT), an inadequate erythropoietin response to anemia persisted. Delayed erythroid recovery after BMT is associated with inadequate erythropoietin levels. Therefore, recombinant human erythropoietin may be useful in the treatment of the anemia associated with both autologous and allogeneic BMT. PMID- 1421382 TI - Pentoxifylline did not prevent transplant-related toxicity in 31 consecutive allogeneic bone marrow transplant recipients. PMID- 1421383 TI - Quinine-associated immune thrombopenia, neutropenia, and renal failure in a patient with Klinefelter's syndrome. PMID- 1421384 TI - Adaptor for Jamshidi needles to enhance penetration of hard bone. PMID- 1421385 TI - Polymerase chain reaction monitoring shows a high efficacy of clinical immunomagnetic purging in patients with centroblastic-centrocytic non-Hodgkin's lymphoma. PMID- 1421386 TI - Problems with the international normalized ratio. PMID- 1421387 TI - Molecular basis of inherited human antithrombin deficiency. AB - Figures 1 and 4 summarize the various AT mutations that have been described. The molecular elucidation, over the past decade, of the various AT deficiency types has provided important new insights into functional-structural relationships of AT. This knowledge, together with data provided by monoclonal antibodies and x ray crystallographic studies of related molecules, has provided important new insights as to how the AT molecule functions in vivo. Finally, such knowledge might, in the foreseeable future, lead to the production of AT molecules that are specifically genetically engineered to be of use in a variety of clinical situations. PMID- 1421388 TI - Breakpoints at 11q23 in infant leukemias with the t(11;19)(q23;p13) are clustered. AB - We have analyzed a series of nine infant leukemias that carry a t(11;19)(q23;p13). They had the morphologic features of acute lymphoblastic leukemia (ALL) and expressed markers typical of B-cell progenitor ALL or pre-B ALL; one coexpressed myeloid markers in addition to lymphoid markers (biphenotypic). Two probes (P/S4 and 98.40) subcloned from a yeast artificial chromosome (YAC) known to span the breakpoint in the t(4;11) were used to investigate DNA isolated from the leukemic cells of these patients. A total of approximately 15 kb of genomic DNA in the vicinity of the probes was examined by conventional Southern blot analysis using a series of restriction enzymes. In eight of the nine cases, the breakpoint could be mapped to an approximately 10-kb BamHI fragment disclosed by hybridization to the P/S4 probe. PMID- 1421389 TI - All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases. AB - We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course ("4 + 7" course), then three "2 + 5" DNR + Ara C courses and maintenance chemotheapy. However, the "4 + 7" course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the "4 + 7" course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the "4 + 7" course. Four patients did not receive this course but received the subsequent "2 + 5" courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1421390 TI - A controlled trial of recombinant human granulocyte-macrophage colony-stimulating factor after total body irradiation, high-dose chemotherapy, and autologous bone marrow transplantation for acute lymphoblastic leukemia or malignant lymphoma. AB - Infections during granulocytopenia are major complications of autologous bone marrow transplantation (ABMT). Since recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) has proved to accelerate bone marrow recovery after cytostatic chemotherapy, we studied its effects on hematopoietic regeneration and on infectious complications after total body irradiation (TBI) and high-dose chemotherapy followed by ABMT. Eighty-one patients with acute lymphoblastic leukemia (ALL) in complete remission (CR) or with non-Hodgkin's lymphoma (NHL) in CR or partial remission were randomized in a double-blind, placebo-controlled trial. They received either rhuGM-CSF 250 micrograms/m2 (Escherichia coli-derived) daily by continuous infusion after ABMT, or placebo. Treatment was continued until the neutrophil counts reached greater than 500/microL for 1 week. The maximum treatment duration was 30 days. Thirty-nine patients in the rhuGM-CSF group and 40 patients in the placebo group were evaluable. The median time needed to reach a neutrophil count of 500/microL was 15 days with rhuGM-CSF and 28 days with placebo (P = .0001). Bacterial infections occurred in 14 (35.9%) of the patients with rhuGM-CSF and in 25 (62.5%) of the patients given the placebo (P = .024). Nine of the 14 bacterial infections in the rhuGM-CSF group and 20 of the 25 infections in the placebo group were diagnosed within the first 10 days after ABMT. Capillary leakage and a reversible fluid retention were seen in five of the rhuGM-CSF-treated patients. Patients treated with rhuGM-CSF had lower serum protein and albumin levels than patients in the placebo group. There was no statistically relevant difference in overall survival between the two groups (P = .47). Relapse occurred in 14 (34%) patients with rhuGM-CSF and in 18 (45%) patients with placebo. We conclude that continuous infusion of rhuGM-CSF after ABMT accelerates the regeneration of granulocytes and reduces the number of bacterial infections. PMID- 1421391 TI - Changes in T-helper cell function in human immunodeficiency virus-infected children during didanosine therapy as a measure of antiretroviral activity. AB - Didanosine has shown activity against the human immunodeficiency virus (HIV) in both children and adults. We prospectively assessed T-helper cell (Th) function as determined by in vitro interleukin-2 (IL-2) production in response to a panel of T-cell stimuli in 22 HIV-infected children before and during didanosine therapy and we correlated the incidence of opportunistic and recurrent bacterial infections with changes in p24 antigen and CD4 counts. Didanosine (270, 360, or 540 mg/m2/d) was administered orally for periods ranging from 8 to 40 weeks (mean, 24 weeks). Five of six asymptomatic patients (Centers for Disease Control P-1) compared with 6 of 16 symptomatic (P-2) patients exhibited improved Th function (greater than threefold increase in IL-2 production to at least 2 of the 4 stimuli) during therapy. Of 12 patients without infections during therapy, 9 (75%) showed improvement in Th function, compared with only 2 of 10 patients with infections (P = .03). Notably, the incidence of infections was not correlated with improvements in CD4 count or decreases in p24 antigen. Improvement in Th function during didanosine therapy is correlated with decreased incidence of infections. Assessment of Th function may provide an additional measurement of immunologic response to antiretroviral therapy. PMID- 1421392 TI - Monoclonal antibody against the common beta subunit (beta c) of the human interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor receptors shows upregulation of beta c by IL-1 and tumor necrosis factor-alpha. AB - High-affinity receptors for human granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 are composed of two distinct subunits, alpha and beta. Each receptor has its own ligand-specific alpha subunit, and the three receptors share the common beta subunit, beta c. Using a transfectant of NIH3T3 cells expressing the high-affinity human GM-CSF receptor, monoclonal antibodies (MoAbs) against beta c were generated. These MoAbs specifically bound to cells bearing beta c and immunoprecipitated the beta c protein of 120 Kd. Using these MoAbs, expression of beta c was examined. It is known that IL-1 augments the proliferative response of a human factor-dependent hematopoietic cell line TF-1 to either GM-CSF, IL-3, or IL-5, and that it upregulates the high-affinity receptors for GM-CSF, IL-3, and IL-5. Antibody binding and immunoprecipitation demonstrated that IL-1 increased cell surface expression of beta c. This enhancement by IL-1 was accompanied by an increased level of beta c mRNA. In addition, we found that tumor necrosis factor-alpha (TNF alpha) also increased the expression of beta c, although it did not augment the proliferative response of TF-1 to GM-CSF, IL-3, and IL-5. PMID- 1421393 TI - Role of monocytes in the expansion of human activated natural killer cells. AB - We have studied the mechanisms underlying expansion of recombinant interleukin-2 (rIL-2)-stimulated natural killer (NK) cells in vitro. A population of NK cells expressing the CD56+/CD3-phenotype (98.9% +/- 0.42%) was obtained from normal human peripheral blood mononuclear cells (PBMNC) by fluorescence-activated cell sorting (FACS). Culture of NK cells in media containing rIL-2 (1,000 U/mL) for 18 days resulted in a population of activated NK cells (ANK) with significantly enhanced cytotoxicity, but only 2.6 +/- 0.56-fold expansion of cell number compared with the starting NK population. Culture of starting NK populations and autologous PBMNC in a Transwell system (Costar, Cambridge, MA), providing separation of the two cell populations by a 0.4-microns pore membrane, resulted in a dose-dependent increase in fold expansion of ANK (expansion = 19.9 +/- 4.0 fold; P < .001; n = 22) significantly greater than that observed when NK were cultured alone. Further experiments using the Transwell system showed that the stimulatory effect of autologous PBMNC on ANK progenitor proliferation resides in the CD14+ monocyte fraction (maximal expansion = 14.5 +/- 1.5-fold; n = 17) and not in the CD5+ T-lymphocyte or CD19+ B-lymphocyte fractions. Direct coculture of purified NK and autologous monocytes in the same compartment, thus permitting cell-cell contact, resulted in significantly greater expansion of the ANK population (30.6 +/- 4.7-fold expansion, P < .001; n = 10) than that observed when NK and monocytes were separated by the Transwell membrane. Finally, depletion of PBMNC of cells bearing CD5 and CD8 by panning on antibody-coated plastic flasks resulted in a starting cell population enriched for NK progenitors and for monocytes. Cultures of this resultant population for 18 days in the presence of rIL-2 yielded an ANK population similar to that obtained when CD56+/CD3- cells obtained by FACS were cocultured with autologous monocytes. These results suggest that proliferation of ANK requires autologous monocytes and is in part mediated by humoral factors, but is enhanced when NK and monocytes are in direct cell-cell contact. Depletion of cells bearing CD5 and CD8 from PBMNC is a single efficient method for obtaining a starting population capable of producing large numbers of ANK in culture that may lead to new therapeutic uses for the ANK population. PMID- 1421394 TI - Calpain activity in patients with thrombotic thrombocytopenic purpura is associated with platelet microparticles. AB - Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and disseminated platelet thrombi throughout the microvasculature. Studies by our group have demonstrated calcium-dependent proteolytic activity (calpain) that is no longer detectable in the serum of patients with acute TTP after their recovery. The purpose of this study was to investigate if the protease activity of TTP was detectable in plasma and, therefore, not an in vitro phenomenon secondary to the formation of serum. Additionally, we looked for evidence of membrane association of the active protease in the patients' samples, which would explain the persistence of its activity in the presence of plasma inhibitors. Acute TTP samples, both serum and plasma, were collected from 10 patients with TTP. Calpain was measured using bioassays for enzyme activity and also by detection of the protein using immunoblotting with an anticalpain monoclonal antibody (MoAb). In all instances, calpain could be detected both functionally and antigenically in the acute TTP sera and plasma. No calpain activity could be detected in any of the controls, although antigenic calpain was detectable in one sample from a patient who had undergone cardiopulmonary bypass surgery. To investigate whether the calpain was associated with microparticles in the plasma, the TTP plasma samples were ultrafiltered and ultracentrifuged. Activity was not lost by passage across a 0.2-micron filter but was detectable only in the pellet following ultracentrifugation. Membrane association of the calpain in the microparticles also was demonstrated using solubilization with Triton X-100. Immunoprecipitation studies demonstrated that the calpain activity could be removed by MoAbs against platelet membrane glycoproteins (IX and IIb/IIa) but not by a MoAb against red blood cell membrane glycophorin. These studies indicate that active calpain is associated with platelet microparticles in plasma from patients with TTP. PMID- 1421395 TI - Characterization of platelet-releasable forms of beta-amyloid precursor proteins: the effect of thrombin. AB - Activated platelets release a potent inhibitor of factor XIa previously identified as a Kunitz proteinase inhibitor domain-containing form of the beta amyloid precursor proteins (beta APP). Two carboxy-terminal truncated forms of the beta APP, beta APP-751 and beta APP-770, are shown to be the predominant isoforms secreted by platelets. The release of beta APP from platelets is responsible for the higher concentration of beta APP in serum compared with plasma, and thrombin dose-response data show that release of beta APP is most consistent with alpha granule localization within the platelet. Thrombin induces a limited and specific proteolysis of platelet-secreted beta APP, resulting in loss of a carboxy-terminal fragment. This phenomena is dependent on both thrombin concentration and duration of incubation and is inhibited by the thrombin specific inhibitor hirudin, characteristics that can be duplicated in a mixture of purified recombinant beta APP-751 and thrombin. A similar effect of thrombin on full-length transmembrane forms of beta APP would result in a membrane-bound remnant containing the intact beta-amyloid protein. PMID- 1421396 TI - Response of human platelets to activating monoclonal antibodies: importance of Fc gamma RII (CD32) phenotype and level of expression. AB - Certain monoclonal antibodies (MoAbs) specific for platelet membrane glycoproteins are known to be capable of activating platelets, and it is generally thought that platelets from normal subjects are equally susceptible to stimulation by such MoAbs. We found that platelets from 20 normal donors varied significantly in their sensitivity to three IgG1 murine MoAbs specific for membrane glycoproteins CD9, GPIV (CD36), and the GPIIb/IIIa complex (CD41), respectively. The response of platelets to these MoAbs was blocked by prior addition of MoAb IV.3 specific for the Fc gamma RII receptor, indicating that activation was Fc receptor mediated. Platelets that responded poorly to these MoAbs failed to bind the MoAb 41H.16, specific for the "responder" form of Fc gamma RII, but platelets that responded well reacted with this MoAb. The average number of Fc gamma RII receptors on platelets from "responders" and "non responders" was approximately the same. However, the number of Fc gamma RII receptors expressed influenced sensitivity of a subgroup of "responder" platelets to the anti-CD41 MoAb. These platelets were judged on the basis of MoAb binding studies to be heterozygous for the two alleles of Fc gamma RIIA. In contrast to their varying sensitivity to IgG1 MoAbs, members of the platelet panel responded equally well to 50H.19, an IgG2a MoAb specific for CD9, and these responses could not be blocked by MoAb IV.3 in the presence of plasma. This appears to be because of dual actions of 50H.19 on platelets: one FcR-dependent and the other complement-dependent. Our findings confirm previous reports that certain IgG1 MoAbs activate platelets through binding of their Fc domains to Fc gamma RII receptors and demonstrate that this response is influenced both by Fc gamma RII phenotype and (in the case of the anti-CD41 MoAb) by the number of Fc gamma RII receptors expressed. The failure of nonresponding platelets to bind detectable amounts of MoAb 41H.16, which is thought to recognize all Fc gamma RII receptors except for one allele of the Fc gamma RIIA gene, is consistent with the possibility that Fc gamma RIIA gene products, but not Fc gamma RIIB or Fc gamma RIIC gene products, are expressed on platelets. PMID- 1421397 TI - Presence of active and latent type 1 plasminogen activator inhibitor associated with porcine platelets. AB - Data from a number of laboratories indicate that human platelets contain type I plasminogen activator inhibitor (PAI-1) primarily in a latent form; however, one report (Biochemistry 28:5773, 1989) indicated that it is predominantly the active form of PAI-1 that is present in and can be purified from an ammonium sulfate precipitate of porcine platelets. To clarify this situation, we investigated and compared the status of PAI-1 in porcine and human platelets. Immunologic analysis of the ability of PAI-1 to form complexes with immobilized t-PA indicated that porcine and human platelets contained 3.7 +/- 0.4 and 1.7 +/- 0.3 U of PAI activity per 10(8) platelets (n = 6; +/- SD), respectively; sodium dodecyl sulfate (SDS)-activation of the lysates increased PAI-1 activity to 10.8 +/- 3.0 and 3.8 +/- 0.5 U per 10(8) platelets. Platelet lysates were also treated with an excess of soluble t-PA, which formed complexes with active PAI-1, whereas the latent form was detected by SDS-polyacrylamide gel electrophoresis and reverse fibrin autography. Furthermore, immobilized t-PA was able to deplete active PAI-1 from the platelet extracts, and the latent form remaining in the absorbed extract could be quantitated by activation with 4 mol/L guanidine. To investigate the differences between our observations and the published data, porcine platelets were extracted, and PAI-1 was partially purified as described in the literature. For quantitative analysis, porcine platelet PAI-1 was also purified to homogeneity using standard chromatographic procedures optimized in our laboratory for endothelial PAI-1, and the purified protein was used to develop an enzyme linked immunoabsorbent assay for porcine PAI-1 antigen. Our results indicate that: (1) latent PAI-1 in concentrated ammonium sulfate precipitates of porcine platelet lysates cannot be detected unless the precipitates are diluted before treatment with denaturants; and (2) active and latent porcine platelet PAI-1 can be separated by gel filtration over molecular sieving columns. In summary, this report documents that PAI-1 in porcine platelets is present in both an active and a latent form. PMID- 1421398 TI - Prothrombin Himi: a compound heterozygote for two dysfunctional prothrombin molecules (Met-337-->Thr and Arg-388-->His). AB - A congenitally dysfunctional form of prothrombin, Prothrombin Himi, shows reduced fibrinogen clotting activity, although it retains full hydrolytic activity toward synthetic substrates. To elucidate the structural abnormality of the variant prothrombin, we first performed genetic analysis of dysprothrombin. Polymerase chain reaction amplification of the exons 8 through 14 of the proband and her family members' prothrombin genes, which code the thrombin moiety, followed by single-strand conformation polymorphism analysis, identified two variant conformers in exon 10 specific to this family. One variant allele detected in the father was inherited by the proband and one of her sisters, and the other detected in the mother was also inherited by them. This result indicates that the proband has two different base pair changes in the gene. Sequencing showed two novel point mutations in the proband's gene. One is a T to C transition at position 8751, resulting in the substitution of threonine for methionine at codon 337 (Thrombin Himi I). The other is a G to A transition at 8904, resulting in the substitution of histidine for arginine at codon 388 (Thrombin Himi II). By sequencing analysis of her parents, it was determined that Thrombin Himi I was inherited from the father and Thrombin Himi II from the mother. These results confirm that Prothrombin Himi is compound heterozygous for two dysfunctional prothrombin molecules. PMID- 1421399 TI - Importance of platelets in experimental venous thrombosis in the rat. AB - Venous thrombosis was induced by ligature of the inferior vena cava in rats whose blood was made hypercoagulable by intravenous (IV) administration of tissue thromboplastin. From a dose-response showing that the administration of increasing doses of tissue thromboplastin resulted in a subsequent progressive increase of thrombus weight, two concentrations of tissue thromboplastin were chosen: a high dose (550 microL/kg, IV) where thrombus formation was optimal and a concentration (7 microL/kg, IV) where tissue thromboplastin-hypercoagulability was intermediate. In both experimental conditions, leukopenia provoked by a myelotoxic drug did not influence the development of venous thrombosis. However, after thrombocytopenia induced by an antiplatelet antiserum, a dramatic decrease in thrombus formation was observed in animals that had been pre-challenged with the lower dose of tissue thromboplastin, whereas decrease in platelet count did not affect venous thrombosis under high thrombogenic challenge. When administered orally 2 hours before thrombosis induction, the ticlopidine analogue clopidogrel showed dose-dependent inhibition of thrombus formation in animals that were pre challenged with a low dose of tissue thromboplastin (ED50 = 7.9 +/- 1.5 mg/kg, orally) but remained ineffective against high tissue thromboplastin-induced venous thrombosis. We further determined the effect of heparin and hirudin, and showed that both of these drugs exhibited a more potent antithrombotic activity after injection of the lower dose of tissue thromboplastin than after injection of a high dose of tissue thromboplastin. Therefore, using our model of stasis and hypercoagulability, platelet activation played a major role in the development of venous thrombosis when the thrombogenitic stimulus was mild. PMID- 1421401 TI - Characterization of adhesion molecules on human myeloma cell lines. AB - In multiple myeloma, malignant plasma cells are localized in marrow and rarely circulate in peripheral blood. To investigate the role of adhesion proteins in this process, we determined the expression and function of adhesion molecules on cell lines derived from patients with myeloma. The U266, ARH-77, IM-9, and HS Sultan cell lines strongly expressed beta 1 and alpha 4 integrins (89% to 98% positive), confirming that VLA-4 is the principal integrin on these cell lines. The U266 and IM-9 cell lines also expressed alpha 3 integrin on 15% to 20% cells. In contrast, all lines lacked cell surface alpha 2, alpha 5, and alpha 6 integrin expression (< 5% positive). These cell lines adhered to fibronectin (20% to 40% specific binding), without significant binding to either collagen or laminin. Adhesion of these cell lines to fibronectin was partially blocked with either anti-beta 1 integrin monoclonal antibody (MoAb) (75% inhibition), anti-alpha 4 integrin MoAb (75% inhibition), or RGD peptide (50% inhibition), but was unaffected by anti-alpha v beta 3 or anti-alpha IIb beta 3 MoAbs. Moreover, the combination of anti-beta 1 plus RGD peptide or anti-alpha 4 plus RGD peptide inhibited binding to fibronectin by 80% and 95%, respectively. Finally, pretreatment and coculture of the IM-9 cell line with interleukin-6 (IL-6) resulted in a 52% decrease in specific binding to fibronectin (30% +/- 6% to 15% +/- 6%; P = .001), associated with a decrease in the number of cells expressing VLA-4 and a decrease in intensity of VLA-4 expression. These data suggest that myeloma cells adhere to fibronectin through VLA-4 as well as through RGD dependent mechanisms, and that this binding can be downregulated by IL-6. Future studies of binding of both myeloma cell lines and freshly isolated tumor cells to extracellular matrix proteins and to marrow stroma may enhance our understanding of localization and trafficking of cells within the bone marrow microenvironment. PMID- 1421400 TI - Variable region gene analysis of an isotype-switched (IgA) variant of chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia of B-cell origin (B-CLL) is generally thought to arise by neoplastic transformation of B lymphocytes, which express CD5 and have features of an early stage of B-cell differentiation. To study isotype-switched B CLL as a potentially more differentiated variant, we performed genetic and functional immunoglobulin (Ig) gene analysis in two cases of CD5+ B-CLL in which the peripheral blood mononuclear cells (PBMC) secreted predominantly IgA (CLL 249) or IgG (CLL-412) when stimulated with pokeweed mitogen in vitro. By cDNA sequencing and by studies of CLL-heterohybridomas, CLL-249 expresses the heavy chain constant region C alpha as anticipated, while CLL-412 expresses C mu, not C gamma. In CLL-249, the expressed VH gene is 98% homologous to VH26, a germline VH3 gene that occurs frequently in the fetal repertoire, and which has been associated with anti-DNA specificity. The VL gene of CLL-249 is a lambda VL gene for which the germline sequence is not known. In CLL-412, the VH gene is 100% homologous to the VH1 gene of a published anti-DNA antibody (21/28), and is probably a germline gene sequence; the VL gene is 100% homologous to 15AVKI, also a germline gene. The supernatant antibody of the CLL-412 heterohybridoma is an IgM-kappa, which reacts with ssDNA and cardiolipin. The CLL-249 heterohybridoma secreted IgA-lambda, which bound none of the antigens tested, a finding that may be related to amino acid differences from the probable germline V genes. The demonstration of an in vivo isotype-switched variant, such as CLL-249, suggests that B-CLL may be a heterogeneous group of clonal disorders, of which less common variants may have features of more differentiated B-cell stages, such as isotype switching. PMID- 1421402 TI - A new in situ hybridization technique for spliced RNA species documents the bone marrow origin of pulmonary macrophages in chronic myelogenous leukemia. AB - Tissue macrophages derive from monocytes of bone marrow origin. Because monocytes from patients with chronic myelogenous leukemia (CML) contain the Philadelphia chromosome (Ph), it seemed probable that tissue macrophages in CML would originate from the malignant clone. Using powerful molecular techniques, we studied pulmonary alveolar macrophages (PAM) from two patients with CML. PAM from Patient 1, a patient in chronic phase studied before bone marrow transplantation (BMT), contained the Ph by Southern blot analysis. Patient 2, an accelerated phase patient, was studied after post-BMT relapse. PAM from this patient not only contained the Ph, but also expressed the BCR/ABL message documented by a new splice junction in situ hybridization technique. This new technique allows detection of BCR/ABL mRNA and determination of splice useage in individual cells. These data confirm the continued replenishing of PAM from peripheral blood monocytes in non-BMT settings and represent the first direct evidence that tissue macrophages are derived from the malignant clone in patients with CML. PMID- 1421403 TI - Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation. AB - To investigate whether somatic hypermutation occurs in multiple myeloma (MM) Ig VH region genes, we have cloned and sequenced the expressed VH genes from five cases of MM. The sequences were obtained after polymerase chain reaction (PCR) on total RNA isolated from the bone marrow, using 5' VH family-specific leader and 3' C gamma- or C alpha-specific primers. MM-specific CDR3 oligonucleotides were produced to isolate VH genes expressed by the malignant plasma cells. In all five cases, the productive Ig gene used the VH3 family. Extensive sequence analysis of multiple independent M13 clones showed no intraclonal variation with no evidence for ongoing somatic hypermutation in MM VH region genes. We were able to identify possible germline counterparts of the expressed VH genes in two cases. Comparison of these genes shows that the MM VH region genes have somatic mutations characteristic for an antigen-driven process. In the other three cases, no close homology could be found with published VH3 sequences. These findings implicate that, in MM, clonal proliferation takes place in a cell type that has already passed through the phase of somatic hypermutation. PMID- 1421404 TI - Cell cycle kinetics in malignant lymphoma studied with in vivo iododeoxyuridine administration, nuclear Ki-67 staining, and flow cytometry. AB - Cell cycle kinetics of malignant lymphoma were investigated using in vivo labeling with iododeoxyuridine (IdUrd) and subsequent flow cytometry (FCM) of IdUrd/DNA and Ki-67/DNA. This approach provides an extensive cell kinetic profile from only one single tumor biopsy, including data upon the percentage of S-phase cells, the IdUrd labeling index (LI), Ki-67-derived growth fraction, duration of the S-phase, duration of the G1-phase, potential doubling time, cell production rate, and total cell cycle time. Tissue samples from 33 patients were studied: non-Hodgkin's lymphoma (NHL; n = 22), Hodgkin's disease (HD; n = 7), and reactive hyperplasia (n = 4). In NHL, the percentage of S-phase cells, LI, growth fraction, duration of the S-phase, and cell production rate were significantly correlated with the histologic malignancy grade according to the Working Formulation (P < or = .02). Data found in HD were not essentially different from those in low-grade NHL and reactive hyperplasia. Remarkably, the duration of the S-phase, the duration of the G1-phase, and the total cell cycle time appeared to be rather independent of histologic malignancy grade within the NHL category. A significant correlation was observed between the IdUrd LI and the percentage of S phase cells, the growth fraction, the potential doubling time, and the cell production rate (P < .001), but not with the duration of the separate cell cycle phases (P > .05). Our data show (1) that it is feasible to obtain detailed information on the in vivo growth characteristics of malignant lymphoma; and (2) that the transition time through the different cell cycle phases widely varies, even within distinct histologic subgroups. PMID- 1421406 TI - Human common acute lymphoblastic leukemia-derived cell lines are competent to recombine their T-cell receptor delta/alpha regions along a hierarchically ordered pathway. AB - Rearrangements of the T-cell receptor (TCR) delta locus are observed in the majority of human B-cell precursor acute lymphoblastic leukemias (ALL) with a striking predominance of V delta 2(D)D delta 3 recombinations in common ALL (cALL) patients. Recently, we and others showed that almost 20% of cALL cases are characterized by further recombination of V delta 2(D)D delta 3 segments to J alpha elements, thereby deleting the TCR delta locus in analogy to the delta Rec/psi J alpha pathway in differentiating alpha/beta-positive T cells. We report here that two human cALL-derived cell lines, REH and Nalm-6, are competent to recombine the TCR delta/alpha locus under standard tissue culture conditions. Analysis of different REH subclones obtained by limiting dilution of the initial culture showed a biased recombination of V delta 2D delta 3 to distinct J alpha elements. During prolonged tissue culture, a subclone acquired growth advantage and displaced parental cells as well as other subclones. Frequently, the DJ junctions of REH subclones contained extended stretches of palindromic sequences derived from modified D delta 3 coding elements. The other cell line, Nalm-6, started the TCR delta/alpha recombination with an unusual signal joint of a cryptic recombinase signal sequence (RSS) upstream of D delta 3 to the 3' RSS of D delta 3. The RSS dimer was subsequently rearranged in all investigated subclones to an identical J alpha element. Both cell lines might become valuable tools to unravel the complex regulation of TCR delta/alpha recombination pathways in malignant and normal lymphopoiesis. PMID- 1421405 TI - Recombinant toxins containing the variable domains of the anti-Tac monoclonal antibody to the interleukin-2 receptor kill malignant cells from patients with chronic lymphocytic leukemia. AB - We have previously shown that the variable domains of the monoclonal antibody anti-Tac [anti-Tac(Fv)] can be fused to derivatives of Pseudomonas exotoxin (PE) or diphtheria toxin (DT) to produce recombinant immunotoxins that kill interleukin-2 (IL-2) receptor-bearing cells. We now report that two of these single-chain recombinant immunotoxins, anti-Tac(Fv)-PE40KDEL and DT388-anti Tac(Fv), are cytotoxic toward peripheral blood mononuclear cells (PBMCs) from patients with chronic lymphocytic leukemia (CLL). In anti-Tac(Fv)-PE40KDEL, anti Tac(Fv) is genetically fused to the amino terminus of PE40KDEL, a recombinant form of PE which contains amino acids 253-608 of PE and the -KDEL mutation at the carboxyl terminus. In DT388-anti-Tac(Fv), anti-Tac(Fv) is fused to the carboxyl terminus of the first 388 amino acids of DT. PBMCs from 14 patients were incubated with the recombinant toxins for 60 hours, and [3H]-leucine incorporation was measured. Anti-Tac(Fv)-PE40KDEL was cytotoxic to 7 of the 14 patient samples, with half-maximal inhibition of protein synthesis (IC50) achieved at 1.2 to 9 ng/mL (1.8 to 13 x 10(-11) mol/L). DT388-anti-Tac(Fv) was cytotoxic to 11 of the 14 samples, with IC50s ranging from less than 1 to 250 ng/mL. DT388-IL-2, in which the first 388 amino acids of DT are attached to IL-2, was marginally cytotoxic toward only 4 of 13 CLL samples tested with IC50s ranging from 100 to 550 ng/mL. Trypan blue staining of cells from several patients indicated that inhibition of protein synthesis correlated with cell death. Binding assays using [3H]-anti-Tac indicated that the CLL cells from nine of the patients contained between 400 and 2,500 sites per cell. Cells from another patient, which were resistant to both anti-Tac(Fv)-PE40KDEL and DT388 anti-Tac(Fv), had less than 100 sites per cell. We conclude that anti-Tac(Fv) PE40KDEL and DT388-anti-Tac(Fv) can kill CLL cells which have low numbers of IL-2 receptors, and should be investigated further for therapy of this disease. PMID- 1421408 TI - Exaggerated cation leak from oxygenated sickle red blood cells during deformation: evidence for a unique leak pathway. AB - An abnormal susceptibility of the sickle red blood cell (RBC) membrane to deformation could compromise its permeability barrier function and contribute to the exuberant cation leakiness occurring during the sickling phenomenon. We examined this hypothesis by subjecting RBCs at ambient oxygen tension to elliptical deformation, applying shear stress in a viscous medium under physiologic conditions. Compared with normal and high-reticulocyte control RBCs, sickle RBCs manifest an exaggerated K leak response to deformation. This leak is fully reversible, is both Cl and Ca independent, and at pHe 7.4 is fully balanced so that Kefflux equals Nainflux. This abnormal susceptibility is also evident in that the K leak in response to deformation occurs at an applied shear stress of only 141 dyne/cm2 for sickle RBCs, as compared to 204 dyne/cm2 for normal RBCs. Fresh sickle RBC membranes contain elevated amounts of lipid hydroperoxide, the presence of which is believed to provide the biochemical basis for enhanced deformation susceptibility. When examined at pHe 6.8, oxygenated sickle RBCs acquire an additional, unbalanced (Kefflux > Nainflux) component to the K leak increment specifically ascribable to deformation. Studies with inhibitors suggest that this additional component is not caused by a known leak pathway (eg, either K:Cl cotransport or the Gardos channel). This abnormal susceptibility of the sickle membrane to development of cation leakiness during deformation probably contributes to the exuberant cation leak taking place during RBC sickling. PMID- 1421407 TI - Characterization of the murine macrophage mannose receptor: demonstration that the downregulation of receptor expression mediated by interferon-gamma occurs at the level of transcription. AB - The macrophage mannose receptor (MMR) is a 175-Kd cell-surface transmembrane glycoprotein that is expressed on tissue macrophages where it functions both to mediate the uptake of mannose-rich glycoproteins and as a phagocytic receptor for bacteria, yeasts, and other pathogenic microorganisms. In this report we describe the cloning of the full-length cDNA of the mouse macrophage mannose receptor and we investigate the level at which interferon gamma (IFN-gamma) downregulates mannose receptor expression. The latter is a marker of the functional state of the cell as high levels are expressed on resident and inflammatory macrophages, whereas cells activated by treatment with IFN-gamma have decreased-to-absent cell surface mannose receptor expression. The murine MMR cDNA contains an open reading frame that predicts a protein of 1,456 amino acids. Transient expression of the protein in heterologous cells shows that this cDNA encodes a functional mannose receptor. The deduced amino acid sequence of this protein has an overall 82% homology with the human mannose receptor and as such, the ectodomain contains an N-terminus that is cysteine-rich followed by a fibronectin type II domain and eight carbohydrate recognition domains (CRDs). The ectodomain is linked to a hydrophobic transmembrane region and a 46-amino acid cytoplasmic tail. All of the eight CRDs are particularly well conserved, especially CRD4, which shows 92% homology with the equivalent region of the human protein. Steady-state levels of murine MMR mRNA were measured in the macrophage cell line J774E, which is known to express the protein at the cell surface. These levels were decreased by a 4- to 8-hour incubation with IFN-gamma, but were almost abolished by overnight treatment with this cytokine. Nuclear run-on experiments showed that IFN-gamma inhibits MMR gene transcription. Therefore, the regulation of mannose receptor expression by IFN-gamma provides a novel system in which to study the mechanisms by which this cytokine represses gene expression. PMID- 1421409 TI - Molecular analysis of human glycophorin MiIX gene shows a silent segment transfer and untemplated mutation resulting from gene conversion via sequence repeats. AB - The human glycophorin (HGp) loci that define the red blood cell surface antigens of the MNSs blood group system exhibit considerable allelic variation. Previous studies have identified gene conversion events involving HGpA(alpha) and HGpB(delta) that produced delta-alpha-delta hybrid genes which differ in the location of breakpoints. This report presents the molecular analysis of HGpMilX, the first example of a reverse alpha-delta-alpha hybrid gene that specifies a newly described phenotype of the Miltenberger complex. A novel restriction fragment unique to the HGpMilX gene was detected by Southern blot hybridization. The structure of the genomic region encoding the entire extracellular domain of the MilX protein was determined. Nucleotide sequencing of amplified genomic DNA showed that a silent segment of the HGpB(delta) gene had been transposed to replace the internal part of exon III in the HGpA(alpha) gene, thereby resulting in the formation of the MilX allele with an alpha-delta-alpha configuration. The proximal alpha-delta breakpoint was found to be flanked by a direct repeat of the acceptor splice site, whereas the distal delta-alpha breakpoint was localized to a palindromic region. This DNA rearrangement, with a minimal transfer of 16 templated nucleotides and a single mutation of untemplated adenyl nucleotide, not only created two intraexon hybrid junctions but transactivated the expression of a new stretch of amino acid residues in the MilX protein. Such a segment replacement may have occurred through the directional transfer from one duplex to the other via the mechanism of gene conversion. The occurrence of HGpMilX as another hybrid derived from parts of parent genes underlines the role of the recombinational "hotspot" in the generation of allelic diversity in the glycophorin family. PMID- 1421410 TI - O-linked oligosaccharides of glycophorins A and B in erythrocytes of two individuals with the Tn polyagglutinability syndrome. AB - Tn polyagglutinability syndrome is an acquired condition where erythrocytes express Tn neo-antigen and become susceptible to hemagglutination by the naturally occurring anti-Tn present in normal sera. Early studies had indicated that O-linked N-acetyl galactosamine was the sole serologic Tn determinant, but more recently O-linked NeuNAc alpha 2, 6GalNAc also has been implicated as a Tn antigen (sialosyl-Tn). However, none of these studies were performed on purified glycoproteins. In this report we examine oligosaccharides of glycophorins A and B purified from Tn erythrocytes of two affected individuals to establish how N- and O-linked saccharides differ from normal. Analysis of carbohydrate composition and treatment with N-glycanase showed that the Asn-linked unit of glycophorin A was not affected. O-linked oligosaccharides were obtained by beta-elimination in the presence of tritiated sodium borohydride. The reduced radiolabeled products were fractionated by Bio-Gel P-2 chromatography, and their structures were investigated by comparison with standards, by monosaccharide quantification, and by neuraminidases of known specificities. The results show that Tn glycophorins from both donors contain intact and truncated forms of trisaccharide and tetrasaccharide NeuNAc alpha 2,3Gal beta 1,3GalNAc and NeuNAc alpha 2,3Gal beta 1,3- (NeuNAc alpha 2,6)GalNAc usually present in glycophorins A and B. The truncated forms include the protein O-linked monosaccharide, GalNAc and disaccharide, NeuNAc alpha 2,6GalNAc (major isomer). The presence of intact glycans in the total population of Tn erythrocytes was confirmed by their susceptibility to T activation after treatment with neuraminidase. The proportion of the four species was not identical in glycophorins of these two donors but, in both, the truncated units predominated and the amount of the disaccharide was approximately one half of that of the monosaccharide. The data are consistent with alterations in UDPGal:GalNAc beta 1,3galactosyl transferase that may have multiple molecular origins and with induction of a specific GalNAc protein alpha 2,6 sialosyl transferase in Tn hematopoietic precursor cells. The molecular basis for these alterations awaits further study. PMID- 1421412 TI - Enhancement of T-cell-depleted bone marrow allografts in the absence of graft versus-host disease is mediated by CD8+ CD4- and not by CD8- CD4+ thymocytes. AB - Transplantation of T-cell-depleted C57BL/6-Nu/Nu ("nude") bone marrow (BM) into C3H/HeJ recipients, conditioned with 8 Gy total body irradiation plus chemotherapy with the myeloablative drug dimethyl myleran, resulted in poor hematopoietic reconstitution 14 days posttransplant, compared with transplantation with T-cell-depleted BM from normal C57BL/6 donors. Hematopoietic reconstitution of "nude" BM could be improved by the addition of (C57BL/6xC3H/HeJ)F1 thymocytes void of graft-versus-host activity. Enhancement of BM allografting by thymocytes is sensitive to low radiation doses (> or = 5.0 Gy) and can be achieved by transplanting the BM 24 hours before the administration of thymocytes. Fractionation of F1 thymocytes by differential agglutination with peanut agglutinin (PNA) and by fluorescence activated cell sorting showed that this hematopoietic enhancing activity is enriched in the unagglutinated (PNA-) thymocyte fraction and is mediated by PNA- CD8+ and not by PNA- CD4+ thymocytes. PMID- 1421411 TI - Silent human immunodeficiency virus type 1 infection: a rare occurrence in a high risk heterosexual population. AB - A group of 58 heterosexual female partners (FP) of human immunodeficiency virus type 1 (HIV-1)-seropositive hemophiliacs was studied by conventional diagnostic methods such as enzyme-linked immunosorbent assay (ELISA) and Western blot analysis to examine whether any had acquired HIV-1 infection through sexual transmission. A subset of 29 FP were asked to answer a detailed questionnaire concerning their health, use of "safer sex" techniques, and other risk factors for HIV-1 infection. They also had additional blood drawn for CD4 cell analysis, viral cultures, nef, gag, and env immunoblots, and polymerase chain reaction (PCR) analysis to assess the occurrence of "silent" HIV-1 infection in a high risk seronegative population. Among the 58 FP, three were found to be HIV-1 seropositive on first testing, with no new seroconversions occurring with subsequent testing in the remaining 55. Two seropositive FP had the additional testing and were found to have positive viral cultures, as well as positive PCR results. All of the seronegative FP (n = 24) who had additional testing were negative in viral culture, had negative immunoblots, and had no HIV-1 nucleic acid sequences detected by PCR. Thus, in this population, silent HIV-1 infection appears to be a rare occurrence and antibody testing seems to correlate with the more sensitive techniques of PCR and viral cultures. PMID- 1421413 TI - Use of recombinant human granulocyte-macrophage colony-stimulating factor in patients with lymphoid malignancies transplanted with unpurged or adjusted-dose mafosfamide-purged autologous marrow. AB - The neutropenia-related morbidity and mortality occurring after autologous bone marrow transplantation (ABMT) is increased by marrow purging procedures. While phase I through III clinical trials showed the enhancing activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil recovery after ABMT with unpurged marrow, controversial results have been reported when purged marrow was used. Therefore, it was the aim of the present study to evaluate the efficacy of rhGM-CSF administration in a group of patients (n = 15) with lymphoid malignancies transplanted in complete remission with mafosfamide-purged (n = 10) or unpurged (n = 5) marrow. Mafosfamide concentrations used for marrow purging were evaluated on an individual basis by means of a recently described technique that destroys the granulocyte-macrophage (granulocyte-macrophage colony-forming units [CFU-GM]) compartment, but spares 50% of the more primitive stroma adherent colony-forming cells (CFU-Blast). rhGM CSF (10 micrograms/kg/d) was started within 24 hours of ABMT and administered in a 4-hour infusion daily until the absolute neutrophil count (ANC) reached 500 x 10(6)/L and then for 7 more days. Patients receiving mafosfamide-purged or unpurged marrow failed to show any difference in terms of median number of days required to achieve an ANC > or = 500 x 10(6) (13 v 14.0, P > .4) cells/L. As compared with retrospective controls, granulocytic recovery was reduced by a median time of 11 (P < or = .0005) and 5 (P < or = .0005) days for patients grafted with purged and unpurged marrow, respectively. The number of CFU-GM (mean +/- SD) infused per kilogram of body weight was significantly lower in patients who received purged autografts as compared with those receiving unpurged autografts (0.85 +/- 0.79 x 10(4) v 15.7 +/- 9.2 x 10(4), P < or = .0005). The dose of CFU-GM progenitors infused per kilogram of body weight did not correlate (r = .031, P > .05) with the time required to reach an ANC > or = 500 x 10(6) cells/L. The number of CFU-Blast (mean +/- SD) infused per kilogram of body weight was not significantly different between patients who received purged or unpurged autografts (5.05 +/- 2.51 x 10(3)/kg v 6.18 +/- 2.66 x 10(3)/kg, P < or = .375). A statistically significant correlation (r = -.658, P < or = .05) was observed between the number of CFU-Blast infused and the number of days required to reach an ANC > or = 500 x 10(6) cells/L.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1421414 TI - Analysis of T-cell receptor variability in transplanted patients with acute graft versus-host disease. AB - T lymphocytes play a pivotal role in graft-versus-host disease (GVHD) and largely contribute to the graft-versus-leukemia (GVL) effect. Most mature T lymphocytes specifically recognize antigens through the alpha/beta T-cell receptor (TCR). Each alpha/beta TCR chain includes a constant region and a variable region, the latter being encoded by V-J alpha or V-D-J beta rearranged gene segments. To better characterize T cells involved in GVHD, V alpha and V beta gene segment usage was analyzed, after cDNA amplification, in peripheral blood mononuclear cells (PBMC) and skin samples from three patients with grade II cutaneous GVHD. At time of GVHD diagnosis (days 11, 22, and 25), when first signs of engraftment were detectable, virtually all V alpha and V beta subfamilies were represented in PBMC RNAs of the three recipients. These results suggest that diversified TCR gene segment expression is observed early after allogenic bone marrow transplantation (alloBMT). Lymphocytes infiltrating GVHD skin also expressed a large series of V alpha and V beta subfamily specificities. However, analysis of the V alpha and V beta amplified products showed substantial differences between PBMC and the skin lymphocyte RNAs. These observations indicate that a large variety of T lymphocytes are present at the disease site, while some of them may be specifically amplified or decreased in response to minor histocompatibility antigens (miHA). Further characterization of the latter T-cell subpopulations should lead to a better understanding of human in vivo responses directed at miHA. PMID- 1421415 TI - Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation. AB - Busulfan (BU) is a widely used myeloablative and antineoplastic agent in clinical bone marrow transplantation (BMT). The lower incidence of BU-associated toxicities and lower therapeutic effectiveness in young children given BU doses based on body weight (ie, 16 mg/kg) is associated with altered pharmacokinetics of BU; the area under the curve (AUC) of BU concentration versus time is significantly less in these patients than those observed in older children and adults. To optimize BU dosage in young BMT recipients, we developed a dosage regimen based on body surface area (BSA) and determined BU pharmacokinetics and BU-associated toxicities. Seven children (median age, 3.9 years, range, 1.1 to 5.7) undergoing allogeneic or autologous BMT for leukemia received 40 mg/m2/dose BU every 6 hours for 16 doses; BU concentrations were measured in the plasma, and AUCs were determined for each patient after the first and 13th doses. Expressed as a function of body weight, the median BU dosage was 26.4 mg/kg (range, 24.3 to 28.2), a 60% increase over the BU dosage based on body weight. Four patients developed mucositis, and one of them also developed nonfatal hepatic veno occlusive disease (VOD). No patients receiving 40 mg/m2 BU developed neurotoxicity (eg, seizures) or interstitial pneumonitis. Prompt and sustained engraftment was observed in the allogeneic BMT recipients, and late graft failure was not seen. The mean BU AUCs were 1,105 mumol/L.min (range, 790 to 2,080) after the first dose and 1,022 mumol/L.min (range, 632 to 1,860) after the 13th dose of BU, comparable to the AUCs in adults given 16 mg/kg of BU. These studies suggest that, in young children, BSA-based dosing of BU (40 mg/m2) provides drug exposures (AUCs) closer to adult values with acceptable toxicities and may improve therapeutic effects. PMID- 1421416 TI - Eosinophils or large granular lymphocytes. PMID- 1421417 TI - Hematocrit and iron absorption. PMID- 1421418 TI - Serum levels of beta 2 microglobulin and interleukin-6 to differentiate monoclonal gammopathy of undetermined significance. PMID- 1421419 TI - Interference of the IGF system as a strategy to inhibit breast cancer growth. AB - Experimental evidence suggests that human breast cancer cells can be regulated by the IGF-I and IGF-II present in the tumor stromal elements and/or by the endogenous tumor cell IGF-II in a paracrine or autocrine fashion. Thus, blockade of the receptor signalling pathway could lead to diminished tumor growth. Blockade of the type I IGF receptor by a monoclonal antibody (alpha IR3) has been used as a strategy to demonstrate the importance of the IGF pathway. Although alpha IR3 could not block serum-free growth of breast cancer cell lines, it could inhibit anchorage independent growth in most cell lines in the presence of serum. In vivo, alpha IR3 administered at the time of tumor cell inoculation could inhibit MDA-MB-231 tumor formation in athymic mice; however, inhibition of established tumors was not seen. Moreover, alpha IR3 could not inhibit tumor formation of the MCF-7 cell line in vivo. These results suggest that blockade of the type I IGF receptor can inhibit the growth of some breast cancer cells both in vitro and in vivo. Future anti-growth factor strategies include the combination of anti-IGF receptor antibodies with IGF neutralizing modalities, the dual blockade of growth factor receptors (epidermal growth factor receptor and type I IGF receptor), and combinations of steroid hormone antagonists and anti growth factor treatments to maximize tumor inhibition. PMID- 1421421 TI - Can the insulin-like growth factors regulate breast cancer growth? AB - Many laboratories have demonstrated that polypeptide growth factors stimulate human cancer cell growth in experimental systems. Despite this observation, a central question remains: can inhibition of peptide growth factor action inhibit tumor growth in humans? To answer this question, several other concerns must first be addressed. Which growth factors are critical for tumor growth? What are the specific cellular effectors for each growth factor? Can feasible therapies be designed to interrupt growth factor pathways? This issue of Breast Cancer Research and Treatment explores the relevance of the insulin-like growth factors to breast cancer cell growth. PMID- 1421420 TI - Insulin-like growth factor expression in breast cancer epithelium and stroma. AB - The insulin-like growth factors (IGFs) are mitogens for many cancer cell types. In breast cancer cells, IGF-I and IGF-II have both been shown to stimulate cell proliferation. However, IGF-I mRNA has not been found in human breast cancer cell lines, making it unlikely that IGF-I is commonly expressed as an autocrine growth factor for breast cancer cells. Nevertheless, IGF-I mRNA can be detected in breast cancer tissue samples, and in situ hybridization studies have shown that the message originates from the stromal cells adjacent to normal lobules. IGF-II, on the other hand, has been detected in some breast cancer cell lines. In the estrogen receptor positive cell line T47-D, IGF-II mRNA was induced by estradiol. Furthermore, transfection of an IGF-II expression vector into a previously estrogen-dependent cell line resulted in hormone independent growth. Thus, IGF-II can be expressed as an autocrine growth factor in some breast cancers and its expression may, in part, result in hormone independence. Finally, stromal cells obtained from breast tissues showed that IGF-I was commonly expressed in fibroblasts derived from non-malignant biopsy specimens, while IGF-II mRNA was detected in fibroblasts adjacent to malignant tissue. These studies suggest that IGF-II expression may be important in both autocrine and paracrine regulation of breast cancer cell growth. PMID- 1421422 TI - Expression of IGF-I and IGF-II mRNA in breast tissue. AB - Expression of IGF-I and IGF-II was studied in human breast cancer tissues by in situ hybridization. IGF-I mRNA was detected only in stromal cells adjacent to normal breast epithelial cells. Stromal cells associated with the tumor cells did not contain IGF-I, nor did malignant or benign breast epithelial cells. In contrast, IGF-II mRNA was found in both the malignant epithelial cells and their adjacent stromal cells. These data imply that stromal cells associated with breast epithelium may switch expression from IGF-I to IGF-II during breast cancer evolution. This appearance of IGF-II expression may identify cancer-associated stromal cells that have a fetal phenotype. PMID- 1421423 TI - IGF-I and IGF-II expression in human breast cancer xenografts: relationship to hormone independence. AB - Although the growth of some estrogen receptor (ER) positive breast cancers can initially be hormonally manipulated, all will eventually escape hormonal control. It is possible that the expression of polypeptide growth factors is initially under the control of steroid hormones, while the hormone unresponsive state is characterized by constitutive expression of growth factors. We studied the relationship between hormone responsiveness and IGF expression in xenograft models. The ER+ T61 xenograft was established from a primary breast cancer and has been continually passaged in athymic mice. ER+ MCF-7 cells and ER-MDA-MB-231 cells were grown in tissue culture and then inoculated into athymic mice. ER+ xenograft growth was regulated by estrogen, but with opposite results--T61 xenografts are inhibited by estrogen, while MCF-7 xenografts require estrogen for tumor formation. All xenografts expressed type I and II IGF receptors. Although T61 xenografts also express an alternatively spliced IGF-I mRNA, its expression was not regulated by estrogen. Both xenografts expressed IGF-II in a hormonally regulated manner--T61 levels were depressed by estrogen, while MCF-7 levels were increased. Thus, in these model systems, xenograft regulation of tumor growth is accompanied by parallel changes in IGF-II expression. In the estrogen independent MDA-MB-231 cells, IGF-II was constitutively expressed. These data show that IGF II expression correlates with estrogen treatment, suggesting that autocrine expression of IGF-II may mediate estrogen-regulated cell growth. PMID- 1421424 TI - Interactions of pro-cathepsin D and IGF-II on the mannose-6-phosphate/IGF-II receptor. AB - The mannose-6-phosphate (Man-6P)/IGF-II receptor is a multifunctional receptor which binds with a high affinity on distinct sites two strikingly different classes of ligands: IGF-II, and Man-6P bearing molecules such as lysosomal enzymes or other biologically relevant ligands (TGF beta precursor, EGF receptor, proliferin...). Binding of each ligand on its cognate site is severely decreased in the presence of the other type of ligand, thus revealing that the two distinct sites are strongly interacting (steric hindrance, conformational change). Any imbalance in ligands and receptor concentration in various pathological situations (transformation, tumor, altered hormonal levels...) is thus likely to perturb their associated biological functions in the targeting and routing of lysosomal enzymes or Man-6P ligands or in the autocrine/paracrine IGF-II--induced cellular responses. PMID- 1421425 TI - Type 1 IGF receptor in human breast diseases. AB - The first step of the action of IGF1 and IGF2 (IGFs) is their binding to membrane receptors. IGF binding sites have been characterized by competitive binding and cross-linking techniques in human breast cancer cell lines as well as in human breast cancers and in human benign breast diseases. IGF2 is a good competitor of 125I-IGF1 binding to IGF1-R; insulin competes but with a potency 1/100 lower than the IGF1 potency. Chemical cross-linking experiments revealed that the apparent molecular weight of the IGF1-binding sites is 130,000. Alpha IR-3, a murine monoclonal antibody against the IGF1-R, blocks IGF1-binding to this receptor. This antibody inhibits the IGF1-stimulated growth of breast cancer cells. Therefore, the IGF1 specific binding sites correspond to the previously described type 1 IGF receptors (IGF1-R) in normal tissues. Cross-linking experiments with labeled IGF2 resulted in a major band of apparent Mr 260,000-270,000 that was inhibited by unlabeled IGF2 but not by insulin, and corresponds to the type 2 IGF receptor; a second band of apparent Mr 130,000 was inhibited by excess IGFs and insulin (Type I receptor). The alpha-IR3 inhibition of the IGF2 mitogenic activity suggest that IGF1-R partially mediates the growth effect of IGF2 in these cells. We and others have demonstrated that most breast cancer cell lines contain IGF1-R.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421428 TI - A phase II study of sulofenur (LY186641) in gastric cancer. AB - Sulofenur is a novel diarylsulfonylurea with proven anti-tumor activity in murine tumor models. In this phase II study in patients with advanced gastric or gastroesophageal adenocarcinoma, 17 patients were treated with sulofenur orally at 700 mg/m2 for 14 days every 3 weeks. No tumor responses were seen. The main toxicities were anemia, methemoglobinemia and abnormalities in liver function tests. These toxicities precluded dose escalation. However, plasma levels of sulofenur, and its hydroxy and keto metabolites were probably insufficient to exert anti-tumor effect in comparison with data from murine studies. Further structure-activity studies are warranted. PMID- 1421427 TI - Tamoxifen reduces serum insulin-like growth factor I (IGF-I). AB - Antiestrogens are widely used in the management of hormonally responsive breast cancer in both adjuvant and palliative settings, and are currently being evaluated as chemopreventive agents. The classical mechanism of action of these drugs involves inhibition of estrogen-stimulated neoplastic cell proliferation by blockade of estrogen receptors present on breast cancer cells. This paper reviews recent clinical and laboratory data that suggest that the commonly used antiestrogen tamoxifen also acts to reduce serum IGF-I levels. Estrogens appear to play a permissive role in growth hormone (GH) release by the pituitary gland and GH is known to stimulate IGF-I expression by hepatocytes. It is therefore possible that blockade of estrogen receptors in the hypothalamic-pituitary axis by tamoxifen interferes with GH release, leading to reduced hepatic IGF-I expression. In view of results suggesting that IGF-I is a more potent mitogen than estradiol for breast cancer cells and data demonstrating a positive correlation between estrogen receptor level and IGF-I receptor level of breast cancer cells, the IGF-I lowering effect of tamoxifen may contribute to the cytostatic activity of the drug. The interrelationships between steroid hormone physiology and IGF-I physiology may have relevance to a variety of commonly used treatments for hormonally responsive cancers. PMID- 1421426 TI - Progestin regulation of insulin and insulin-like growth factor I receptors in cultured human breast cancer cells. AB - Recent studies indicate that the insulin receptor (IR) content is higher in breast cancer cells than in normal mammary epithelial cells. This observation has been made both in tissue specimens from patients with breast cancer, and in various human cultured breast cancer cell lines. Investigations have now been undertaken to understand the role of progestins in the regulation of the IR and the closely related insulin like growth factors-I receptor (IGF-I-R). Pretreatment of T-47D cultured human breast cancer cell lines with progestins induced a time and dose dependent increase in IR content. This increase was due primarily to an effect of progestins to increase IR mRNA levels. Other steroid hormones including glucocortocoids, estrogen, and testosterone were without effect. In contrast to their up-regulation of the IR, progestins down-regulated the IGF-I-R at the level of mRNA. An analysis of the processes involved revealed that progestins increased the biosynthesis of a ligand for IGF-I receptor, IGF II. IGF-II in turn down-regulated the IGF-I-R. Thus these studies indicate that progestins have important effects on both the IR and the IGF-I-R. The effects of progestins on these and other growth factor receptors, therefore, may have an important role in the biology of breast cancers. PMID- 1421429 TI - Hydroxyurea modulates 5-fluorouracil antineoplastic activity in advanced head and neck carcinoma pretreated with chemotherapy. AB - After informed consent 21 patients with advanced head and neck cancer resistant to folinic acid/5-fluorouracil (FA/5FU + cisplatin) were treated with weekly FA/5FU plus low dose hydroxyurea (HU) to evaluate if HU could further modulate 5FU antineoplastic activity. Five patients achieved a partial response (23.8%) which was short-lived (mean duration 6.5 months). Three patients (14%) had stable disease and 13 (62%) progressed. Among responders, four patients had epidermoidal carcinoma and one had clear cell carcinoma. Treatment was well tolerated and 5FU related toxicity was not apparently worsened by the addition of HU. The most frequent toxicities were nausea/vomiting (81%), diarrhea (52%) and leukopenia (57%). Grade 3 nausea/vomiting and leukopenia were recorded in only 19 and 9% of cases, respectively. One patient had grade 1 cutaneous toxicity and a second patient showed a hand-foot syndrome. These results suggest that HU may further positively modulate 5FU antineoplastic activity. PMID- 1421431 TI - Late doxorubicin cardiotoxicity. AB - The occurrence of late congestive heart failure (CHF) as the first clinical manifestation of doxorubicin-induced cardiac toxicity is unusual in children and very rare in adults. However, subclinical cardiac dysfunction is commonly detected in children years after treatment with doxorubicin containing regimens. We report a 58 year old woman who developed stage IV CHF 7 years after completion of doxorubicin treatment for carcinoma of the ovary. Occult cardiac dysfunction was first demonstrated by radionuclide angiography 6 years prior to the occurrence of the clinical manifestations. This unique course of the disease and the management of the CHF are discussed. PMID- 1421430 TI - Potential antineoplastic activity of keto-C-glycosides--a new family of cytostatic agents. AB - We have examined the biological activity of keto-C-glycosides (KCGs), a new family of drugs displaying antiproliferative and cytotoxic properties on tumor cells. KCG1, the most powerful drug tested on epithelial derived neoplastic cells, was 25-125 times more cytostatic on epithelial cells than on lymphoma. By contrast, KCG10 proved to be more cytostatic on lymphoma than on epithelial cells. Correlations were found between the cytostaticity of KCGs and their lipophilicity, and are discussed within the framework of the structure-activity and the structure-selectivity relationships. PMID- 1421432 TI - Cortical blindness--a catastrophic side effect of vincristine. AB - The term 'cortical blindness' indicates loss of sight due to bilateral lesions of the occipital lobes. It is a rare, but severe, side effect of chemotherapeutic agents. Cortical blindness was diagnosed in a 67 year old woman with leiomyosarcoma of the large bowel, treated by vincristine-containing chemotherapy. Cortical blindness without focal neurological signs and with two repeated normal brain computed tomography scans, in which there was no structural damage to the occipital lobes, suggests a metabolic or toxic reaction as a cause in our patients. The temporal relationship between vincristine treatment and cortical blindness implicates vincristine as the possible causative agent for this catastrophic phenomenon. PMID- 1421433 TI - Cisplatin-related Lhermitte's sign. AB - The sensation of a sudden electrical impulse travelling along the spine to the legs and feet on flexion of the neck has been known as Lhermitte's sign. Lhermitte's sign, as part of cisplatin-related neurotoxicity, was observed in four patients, with ovarian or lung cancer, simultaneously with peripheral neuropathy, after a dose of 375-700 mg/m2. The dose intensity (DI) of cisplatin in our patients ranged from 12.5 to 26.9 mg/m2/week. No direct relationship was found between DI and the timing of Lhermitte's sign. Other relevant causes for this sign were ruled out. The mechanism responsible for the development of Lhermitte's sign is unclear. Interruption of treatment with cisplatin may not prevent the appearance of Lhermitte's sign. In most of the reported cases in the literature this sign developed after the end of cisplatin courses. PMID- 1421434 TI - Hydroxyurea-induced cell death in human T lymphoma cells as related to imbalance in DNA/protein cycle and deoxyribonucleotide pools and DNA strand breaks. AB - The aim of this study was to elucidate the mechanism(s) behind the cellular toxicity of therapeutic concentrations of hydroxyurea (HU). Treatment of human T lymphoma cells (CCRF-CEM) with 60-100 microM of HU for 24 h decreased the growth rate by 90% due to accumulation of cells in early S phase. It induced a marked imbalance in both the DNA/protein cycle (as measured by two-parameter flow cytometry) and the deoxyribonucleotide (dNTP) pools. HU treatment did not enhance the frequency of DNA single-strand breaks (SSBs), as measured by the alkaline unwinding technique. Cell viability was unaffected. However, removal of HU led to 10-15% cell loss during the following 12 h period in parallel with increasing SSBs, and a rapid progression of cells through S and G2 stages. The unbalanced DNA to protein content per cell and the dNTP pools were normalized 6-12 and 24 h after removal of HU, respectively. These results show that marked changes in the DNA to protein ratio and dNTP pools alone are not directly lethal, but when combined with a high replicative DNA synthesis rate, as found after removal of HU, apparently lead to elevated cell death. PMID- 1421435 TI - A comparative study of the antitumor activities of 5'-deoxy-5-fluorouridine and its prodrug trimethoxybenzoyl-5'-deoxy-5-fluorocytidine (Ro09-1390) on human digestive organ cancer xenograft lines transplanted into nude mice. AB - 5'-Deoxy-5-fluorouridine (5'-DFUR) is one of the oral fluoropyrimidines widely used in the treatment of gastric, colorectal and breast cancers in Japan. 5'-DFUR is converted to 5-fluorouracil by pyrimidine nucleoside phosphorylase in the tumor. 5'-DFUR has toxic effects on the intestine and may cause severe diarrhea. Trimethoxybenzoyl-5'deoxy-5-fluorocytidine (Ro09-1390) is a prodrug of 5'-DFUR, which was developed to reduce the intestinal toxicity of 5'-DFUR. The present study was designed to assess the antitumor activity and spectrum of Ro09-1390, and to compare its efficacy with that of 5'-DFUR. Six digestive organ cancer xenograft lines (two gastric, one esophageal, one colorectal, one gall bladder and one bile duct cancers) were s.c. transplanted into nude mice. The agents were orally administered daily for 14 days at doses of 0.08-0.64 mmol/kg (1-8 times the maximal clinical dose of 5'-DFUR). Both 5'-DFUR and Ro09-1390 significantly inhibited the growth of two gastric cancer lines, and the IC50's for Ro09-1390 in both lines were lower than the respective values for 5'-DFUR. The esophageal, colorectal, gall bladder and bile duct cancer lines, however, were resistant to both agents. 5'-DFUR at 0.64 mmol/kg significantly inhibited the growth of these cancers, but with high mortality, and most mice receiving this dose died within 14 days after the start of therapy, suffering from severe diarrhea and body weight loss. Ro09-1390 at the same dose resulted in low mortality, but evidenced similarly low antitumor activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421436 TI - Expression of resistance to etoposide and vincristine in vitro and in vivo after X-irradiation of ovarian tumor cells. AB - Two human ovarian carcinoma cell lines (JA-T/P and SK-OV-3/P) were exposed to 10 fractions of 5 Gy X-irradiation in vitro. Surviving populations generated sublines designated DXR-10 which expressed significant resistance to etoposide (VP-16) and vincristine (VCR), but not to adriamycin (ADR) or acute X irradiation, as judged by clonogenic assays. JA-T/P and JA-T/DXR-10 tumor cells were xenografted into nude mice and treated with a single dose of VCR (1.8 mg/kg), VP-16 (24.5 mg/kg) or ADR (10.0 mg/kg) and 48 h later the surviving clonogenic cells in each tumor were quantitated. Significantly fewer colonies grew from the JA-T/P xenografts treated with either VCR or VP-16, as opposed to the JA-T/DXR-10 tumors, whilst comparable colony numbers were recorded after ADR treatment. These data suggest that the resistant phenotype following exposure to fractionated X-irradiation in vitro is also expressed in vivo. PMID- 1421437 TI - Influence of O6-methylguanine on DNA damage and cytotoxicity of temozolomide in L1210 mouse leukemia sensitive and resistant to chloroethylnitrosoureas. AB - Temozolomide is a new anticancer agent which in the early clinical investigation has shown promising antitumor activity. It decomposes spontaneously to the active metabolite of DTIC (MTIC). Temozolomide is more cytotoxic against L1210 than against a subline L1210/BCNU, resistant to chloroethylnitrosoureas. Using [methyl 3H] temozolomide we found that after 1 h exposure the amount of O6-methylguanine (O6mGua) was twice as high in L1210 than in L1210/BCNU whereas the amount of N7 mGua was approximately the same in the two cell lines. O6-alkylguanine DNA alkyltransferase (AT) levels were higher in L1210/BCNU than in L1210, supporting the view that the resistance to methyltriazenes is probably related to the efficient repair of O6mGua in L1210/BCNU. Exposure of L1210/BCNU cells to 0.4 mM O6mGua for 24 h resulted in a depletion of AT and in a higher temozolomide induced cytotoxicity. In the sensitive cell line L1210, temozolomide activity was not potentiated by O6mGua pretreatment. Moreover, in L1210/BCNU, O6mGua increased DNA single-strand breaks caused by temozolomide, suggesting that O6-guanine alkylation induces an excision repair mechanism in cells depleted in AT. PMID- 1421439 TI - SDZ PSC 833 and SDZ 280-446 are the most active of various resistance-modifying agents in restoring rhodamine-123 retention within multidrug resistant P388 cells. AB - Multidrug resistance (MDR) of tumor cells may result from overexpression of P glycoprotein (Pgp) but may be down-modulated by resistance-modifying agents (RMAs). The cyclosporin SDZ PSC 833 and the cyclopeptolide SDZ 280-446 were found to be the strongest RMAs known to date for restoring the sensitivity of MDR cells to anticancer drugs, as well as for restoring their retention of daunomycin, a fluorescent anthracycline. Using rhodamine-123 (Rhod-123), another fluorescent probe of Pgp function which also differentiates sensitive and MDR cells, several RMAs were compared for their capacity to inhibit Pgp function. At variance with the data obtained with the daunomycin probe, a series of RMAs did not detectably restore Rhod-123 retention by the MDR cells. With the remaining RMAs, achieving the same levels of Rhod-123 retention required 3 times lower RMA concentrations when the RMA was added to the MDR cells for both the initial uptake and the efflux of Rhod-123 rather than for its uptake only. Nevertheless, the data emphasized the large superiority of SDZ PSC 833 and SDZ 280-446 over all other RMAs. PMID- 1421438 TI - Interferon modulation of 5-fluorouracil: use in neoadjuvant therapy inhibits experimental liver metastases in nude mice. AB - Experimental liver metastasis was studied in 4-5 week old athymic nude mice that were injected intrasplenically with a human colorectal tumor cell line (LoVo). A treatment schedule combining 5-fluorouracil and interferon (IFN) was previously shown to inhibit liver metastases. When this treatment was delayed until after splenectomy at 1, 2 and 3 weeks after tumor cell injections, liver metastases were not inhibited. However, when IFN was given during the interval between tumor cell injections and splenectomy (as neoadjuvant therapy), liver metastases were inhibited in the 2 and 3 week groups, but not in the 1 week group. PMID- 1421440 TI - Cyclophosphamide-induced suppressor cells in nude mice. AB - Lymphocytes regenerated after treatment with a high dose of cyclophosphamide (CY) were characterized in nude mice. Ten days after a single injection of 200 mg/kg CY into nude mice, regenerated spleen cells suppressed in vitro primary and second antibody production against sheep red blood cells. The CY-treated spleen cells exhibited normal natural killer (NK) activity, very low B and T cell content, but increases in cell surface charge [electrophoretic mobility (EPM)] and histamine receptors. The suppressor cells could not be removed by treatment with anti-Thy-1 plus complement (C), or treatment with antiasialo GM1 (aGM1) plus C, which abrogated NK activity. It was concluded that CY-treated spleen cells, which exhibited high EPM and histamine receptors, comprise the natural suppressor cells which are Ig-, Thy-1- and aGM-1. PMID- 1421441 TI - A diapause associated protein of the pink bollworm Pectinophora gossypiella Saunders. AB - A diapause associated protein was electrophoretically isolated from the hemolymph of diapausing last instar larvae of the pink bollworm Pectinophora gossypiella. This protein (M(r) approximately 490,000, glycolipoprotein) was given the name Pectinophora diapause protein (PDP). It is composed of one subunit (M(r) 103,000). The concentration of PDP increased dramatically in the hemolymph of diapausing larvae from 17.4% in prediapause (PD) phase to 29.2% in early diapause (ED) phase reaching a level of 38.6% in larval hemolymph of middiapause (MD) phase. The concentrations of total proteins in the hemolymph of active feeding (A), PD, ED, and MD larvae were 69.8, 106,6, 113.3, and 118 mg/ml, respectively, while those in the fat body of the same larvae were 7.1, 7.4, 8.8, and 4.5 mg/g, respectively. In Pectinophora a drop in the concentration of fat body proteins coincided with a corresponding increase in hemolymph proteins, which suggests an active release of protein from the fat body into the hemolymph during the development of diapause. A partial amino acid sequence of pectinophorin showed the first 15 amino acids starting from the amino terminus of the peptide chain: N ALA-LYS-THR-ILEU-VAL-GLU-ASN-MET-PRO-PRO-THR-PRO-LEU-ASN-ALA-C. PMID- 1421442 TI - Development of specific RIA and ELISA to study trypsin modulating oostatic factor in mosquitoes. AB - Trypsin modulating oostatic factor (TMOF), a decapeptide (H-YDPAPPPPPP-OH) that signals the termination of trypsinlike enzyme biosynthesis in the mosquito midgut, was covalently bound to Keyhole Limpet Hemocyanin using N hydroxysuccinimide and dicyclohexylcarbodiimide. Polyclonal antibodies raised in rabbits against this conjugate were used to develop specific RIA and enzyme linked immunosorbent assay (ELISA) to detect the peptide hormone in female Aedes aegypti. TMOF and its analogs TMOF(B) (H-DYPAPPPPPP-OH), P4 (H-YDPAPPPP-OH), P1 (H-YDPAP-OH), and poly-L-proline were tested with the antiserum. The antiserum fully recognized TMOF and partially recognized P4. Using both RIA and ELISA, we report that the amount of TMOF in the mosquito ovary is 100 +/- 20 ng (S.E.) and 96 +/- 1.4 ng (S.E.), respectively, for each assay. Minute quantities of TMOF a thousandfold lower than in the ovary were found in the mosquito brain, indicating that the hormone is probably not neural but ovarian in origin. PMID- 1421443 TI - Oral toxicity to flesh flies of a neurotoxic polypeptide. AB - An insect selective neurotoxic polypeptide from venom of the scorpion Androctonus australis (AaIT, M(r) 8,000) was shown to cross the midgut of the flesh fly Sarcophaga falculata, using assays of oral toxicity, column chromatography, and microscopic autoradiography of the native and radioiodinated toxin. AaIT induced paralysis of flies within 1-2 h after oral administration, with a lethal dose (LD50) of 10 micrograms/100 mg of body weight. Oral toxicity was about 0.14% of toxicity by injection. Hemolymph collection 70-85 min after feeding flies with [125I]AaIT showed that 5% of ingested radioactivity appeared in hemolymph. Most of this represented degradation products, but included about 0.3% of the chromatographically intact toxin. In contrast, hemolymph of identically treated lepidopterous larvae (Manduca, Helioverpa [= Heliothis]) contained degradation products but no intact toxin. [125I]AaIT was shown to cross the midgut of Sarcophaga through a morphologically distinct segment of the midgut previously shown to be permeable to a cytotoxic, positively charged polypeptide of similar molecular weight. These results suggest that Sarcophaga midgut contains a morphologically and functionally distinct segment that transports small peptides, and that employment of neurotoxic polypeptides for insect control may be feasible. Activity might be greatly improved through modification and metabolic stabilization of active peptides. PMID- 1421444 TI - Anthropometric assessment of the nutritional status of patients with liver cirrhosis in an Italian population. AB - A poor nutritional status has repeatedly been described in advanced liver cirrhosis, but the exact prevalence of the defect and its relation to the aetiology and severity of liver disease in the Italian population are only partly known. Anthropometric measurements were carried out in 200 patients with cirrhosis (135 M, 65 F). Liver disease was related to alcohol abuse in 77 cases, but most patients had stopped alcohol for at least 6 months before study. In comparison to a normal elderly Italian and to an age-matched North-American population, 5 to 45% of male patients with cirrhosis and 10 to 30% of females had signs of malnutrition, the proportion being variable according to the test used. Male patients showed a remarkable reduction in muscle mass (30-45% of patients, mainly in the presence of moderate-to-severe or severe liver failure), whereas female patients showed a more remarkable reduction of fat stores (15-30% of cases), with advancing liver failure, and a less severe reduction in muscle mass. No direct effect of alcohol was demonstrated in this selected population. PMID- 1421445 TI - Clinicopathological assessment of gastric biopsy samples of patients with Helicobacter pylori infection--metronidazole resistance and compliance problems in the United Arab Emirates. AB - The significance of Helicobacter pylori (HP) infection was assessed prospectively in forty-two patients with dyspepsia using histological, bacteriological and biopsy urease techniques. Thirty-eight patients (90.5%) were positive for HP infection and were treated with bismuth subcitrate (De Nol), tinidazole and doxycycline. HP was present in the antrum, corpus, fundus, duodenum and gastric juice in 36, 26, 23, 2 and 2 patients respectively (p < 0.01, X2 test). Histological assessment yielded more positive identifications of HP than the urease test (36 vs 28 positive cases, p < 0.01, McNemar's X2 test), while histology and bacteriology were virtually identical (38 vs 37 of 41 pairs, p > 0.5, X2 test). There was a good correlation between bacterial and polymorphonuclear leucocyte (PMNL) counts per high power field (r = 0.8; p < 0.001; n = 34 pairs). There was resistance to metronidazole in 10 out of 16 isolates, but no resistance was recorded against tetracycline (p < 0.001, X2 test). Among the sixteen patients who attended follow-up endoscopy, there was clinical improvement and no evidence of HP in 5 individuals (31.25%). One patient had amelioration of his symptoms, 5 experienced no change and in 5 their symptoms became worse. Metronidazole resistance may be one of the important factors in the United Arab Emirates and elsewhere. PMID- 1421447 TI - Extrahepatic abdominal hydatidosis: surgical features of 11 cases. AB - We have described 11 cases of rare abdominal localization of hydatosis in the kidney, spleen and serous tissues. The clinical and surgical features have also been discussed. PMID- 1421446 TI - Interdigestive antro-duodenal motor disorders in functional dyspepsia. Associated chronic gastritis correlates with a further motor impairment. AB - The interdigestive antro-duodenal motor activity was studied in 12 dyspeptic patients without gastritis (group A), 12 dyspeptic patients with chronic superficial antral gastritis (group B) and 8 healthy controls (group C) by manometric recording of phases of the interdigestive motility cycle (IDMC) prolonged over 240 minutes. A significantly lower incidence of migrating motor complexes (MMCs) starting from the antrum was observed in dyspeptic patients with gastritis vs dyspeptic patients without gastritis (p = 0.02) and in these latter vs controls (p < 0.01). Likewise, the overall number of MMCs was smaller in patients with gastritis vs controls (p = 0.02). Symptomatic evaluation was performed in the two groups of dyspeptic patients, without detecting any differences in frequency and severity of individual and overall complaints. Our results confirm the role of interdigestive antral motor abnormalities in the genesis of dyspeptic syndrome and suggest that the presence of associated chronic superficial gastritis may correlate with a further motor impairment. PMID- 1421448 TI - The menstrual cycle has no effect on gastrointestinal transit time. Evaluation by means of the lactulose H2 breath test. AB - Gastrointestinal transit time was studied by means of the H2 breath test (after administration of 20 g of lactulose) in 20 healthy women with regular menstrual cycles. The mean transit time measured in the follicular phase of the cycle (M +/ SE = 71.25 +/- 6.69 min) did not differ statistically from that measured in the luteal phase (66.75 +/- 5.49 min). Data were statistically analyzed using Student's t test for paired data and the Wilcoxon Test for non-parametric data. Our results show that, in physiological conditions, female sex hormones do not affect mouth-to-caecum transit time. The H2 breath test is easy to perform and well tolerated; it thus proves particularly suitable for use in women of child bearing age. PMID- 1421449 TI - Antigliadin antibody classes in chronic liver disease. AB - Antigliadin antibody (AGA) subtypes (IgG and IgA class) were tested in sera from 67 patients with chronic liver disease of different aetiology (29 with primary biliary cirrhosis (PBC), 31 with chronic non-A non-B hepatitis, and 7 with autoimmune chronic active hepatitis (CAH) compared with 23 subjects with inflammatory bowel disease (IBD). Nineteen patients with coeliac disease served as positive controls. IgA-AGA alone were found in 3.4% of patients with primary biliary cirrhosis and in 3.2% of non-A, non-B CAH. IgG-AGA alone were found in 1.3% of patients with IBD, in 6.8% of primary biliary cirrhosis and in 14.2% of autoimmune CAH. IgA-AGA and IgG-AGA together were found in 6.8% of PBC and in 1 patient with autoimmune CAH. Jejunal biopsy, performed in 7 out of the 2 patients with both IgA and IgG-AGA, showed the characteristic features of coeliac disease in one subject with autoimmune CAH. The same patient had the highest titre of AGA. In conclusion, these results indicate that AGA (either IgG and IgA) can be present at low titre in chronic liver disease and their presence may be secondary to the liver damage per se. High titres of AGA in chronic liver disease may suggest a real association with coeliac disease. PMID- 1421450 TI - Abdominal attack of hereditary angioedema associated with marked leucocytosis. A case report. AB - Hereditary angioedema (HAE) attacks are not usually associated with an increase of peripheral blood leucocytes. In a 25-year-old woman suffering from HAE a marked leucocytosis (31,000/mm3) with polynucleosis was observed during a severe attack of the disease. Awareness of the underlying disease, physical examination and the results of instrumental investigations allowed for appropriate treatment avoiding invasive procedures. A leucocytosis of the severity observed in our patient suggests that the abdominal attack of HAE can involve the peritoneum as well as the intestinal mucosa. Thus, in a patient with an attack of abdominal pain the presence of leucocytosis does not exclude the diagnosis of HAE. PMID- 1421451 TI - Computed tomography in the identification of gallstones likely to respond to UDCA. AB - An unusual case of a patient with two biliary stones of different densities that responded differently to oral litholytic treatment with ursodeoxycholic acid (UDCA) is reported. The findings confirm, in an unusual experimental model, that CT is useful in the selection of those stones which have a high probability of dissolution under treatment with oral bile acids. PMID- 1421452 TI - Chronic bleeding caused by small bowel angiodysplasia: a problem of recognition and diagnosis. AB - Angiodysplasia of the gastrointestinal tract is a disorder consisting of ectasia of submucosal and mucosal vessels, which causes acute and chronic bleeding. We describe the case of a 58-year-old man with a history of recurrent lower intestinal bleeding and severe anemia. Endoscopy and X-ray examination of the gastrointestinal tract failed to show the source of bleeding. Selective angiography of the superior and inferior mesenteric arteries revealed a vascular ectasia. The patient underwent ileo-cecal resection with remarkable improvement after surgery. PMID- 1421453 TI - Enema reduction of childhood intussusception under ultrasound guidance. PMID- 1421454 TI - Iatrogenic haemobilia and ultrasonography: one more case. PMID- 1421455 TI - Factors that determine the cost and performance of early identification protocols. AB - In this paper, a simple model is used to examine the relation between important factors, such as prevalence of hearing loss, and protocol performance and cost. Protocol hit rate is determined primarily by the hit rate of the screening protocol and follow-up percentage, the percentage of infants who return for diagnostic testing. Many factors influence protocol cost. Not only does absolute cost change as certain model parameters are varied, but the relative cost of different protocols can change as well. The false alarm rate of the screening protocol and the follow-up percentage have the greatest impact on protocol cost. PMID- 1421456 TI - Predictability and reliability of hearing aid benefit measured using the PHAB. AB - This investigation explored the extent to which self-assessed hearing aid benefit measured by the Profile of Hearing Aid Benefit (PHAB) could be predicted from adaptation to hearing loss and/or from communication difficulties reported without amplification. Adaptation to hearing loss was measured using 13 scales of the Communication Profile for the Hearing Impaired (CPHI). These were combined to produce three composite CPHI scores. Results from 58 experienced hearing aid wearers indicated that benefit was significantly related to magnitude of unaided difficulties for all seven PHAB subscales. In addition, one of the three composite CPHI scores contributed to benefit prediction for the two sound perception subscales of the PHAB. Test-retest reliability of PHAB subscale scores was evaluated for 28 subjects using correlations and difference distributions. Reliability was found to be consistent with previous studies but modest. Critical differences were large compared with the anticipated size of benefit differences due to, for example, different hearing aid prescriptions. It is concluded that the PHAB is best suited for group research: when used for individual subjects, the PHAB may not be sensitive enough to detect important differences between hearing aid conditions. PMID- 1421457 TI - Effects of interaural speech-recognition differences on binaural advantage for speech in noise. AB - The relationship between interaural differences in speech-recognition performance and binaural advantage for speech in noise was studied. Subjects were five hearing-impaired listeners with symmetrical pure-tone air-conduction audiograms and significant interaural differences in speech recognition. All subjects repeated nonsense syllables in the presence of competing noise in monaural and binaural conditions. Binaural advantage was calculated as the difference in signal-to-noise ratio that afforded 50 percent correct performance between the monaural and binaural conditions. The results were diverse. Although the majority of the subjects retained some degree of binaural advantage, a conclusive relationship between interaural differences in speech recognition and binaural advantage could not be established. The implications for binaural hearing aid fittings are discussed. PMID- 1421458 TI - Acoustic-immittance screening for detection of middle-ear effusion in children. AB - The purpose of this investigation was to evaluate the sensitivity and specificity of the following acoustic-immittance protocols and their constituent measures for detection of middle-ear effusion in children: (a) tympanometric width; (b) absent ipsilateral acoustic reflex; (c) ASHA guidelines; (d) tympanometric peak pressure; and (e) static-acoustic middle-ear admittance. The middle-ear sample was composed of 82 ears of 54 subjects ranging in age from 3 to 11 years. The control (normal-hearing, normal middle-ear) sample was composed of 53 ears of 53 subjects ranging in age from 3 to 10 years. Each subject was given a complete otolaryngologic evaluation (including pneumotoscopy and/or microtoscopy) and audiologic (including acoustic-immittance) evaluation. In the group of middle ears with normal-hearing sensitivity, the sensitivity and specificity of the ASHA guidelines were 63 percent and 79 percent, respectively. An acoustic-immittance screening protocol, based on all of the individual acoustic-immittance measures, and characterized by high sensitivity and specificity, is proposed. PMID- 1421459 TI - Effects of notch noise bandwidth on the auditory brainstem response to clicks. AB - The effects of notch width of notch masking noise on the auditory brainstem response (ABR) were investigated with ten normal-hearing subjects. Wave V latencies and amplitudes were measured to a click in quiet and in the presence of noise with notches centered around 1000 Hz and 4000 Hz. Notch width was either 0.5, 1.0, 1.5, 2.0, or 2.5 octaves. A 95 dB SPL broadband noise was necessary to mask a 65 dB nHL click at an effective level of 73 dB nHL. All ten subjects at both 1000 Hz and 4000 Hz yielded identifiable responses for the click in quiet and for the 2.5 octave and 2.0 octave conditions, and eight or nine subjects responded to the 1.5 octave notch noise. In contrast, no responses were observed to the 0.5 octave condition, and only three or four subjects responded to the 1.0 octave notch noise. These findings suggest that when ABRs are obtained to 65 dB nHL clicks in notch noise, the notch width should exceed 1.0 octave. Moreover, because of the relatively low amplitudes elicited with the 1.5 octave bandwidth, it appears preferable to select notches that are 2.0 to 2.5 octaves wide. Considering the wide bandwidth required, the high noise levels necessary to mask clicks, high ABR thresholds, and the difficulty setting the signal-to-noise ratio, it appears that tonepips are more promising than clicks in notch noise for assessing frequency specific ABRs. PMID- 1421460 TI - Adaptation of the auditory brainstem response: effects of click intensity, polarity, and position. AB - The aim of this research was to study the effects of several stimulus parameters on adaptation characteristics of the auditory brainstem response (ABR). Recordings were obtained from normal hearing adults to separate trains of 5 rarefaction and 5 condensation clicks with interclick intervals of 10 msec and intertrain intervals of 500 msec at three intensities. Absolute latencies for waves I, III, and V were essentially unchanged by polarity; latency shifts, however, were induced by parametric manipulations of click intensity, polarity, and position in the train. Furthermore, variations in ABR wave morphology appeared with changes in intensity and polarity. Adaptation, as measured by amplitude, was considerable; the measures of adaptation, however, were not related in a simple manner to the latency shifts. The findings indicate that adaptation of the ABR is a consequence of an interplay of central and peripheral processes to click polarity, sequence, and intensity. Finally, the results provide evidence that when fast stimulus presentation rates are used to estimate thresholds rapidly, one must be aware that certain stimulus parameters can alter the ABR waveforms. PMID- 1421461 TI - Otoacoustic emissions, audiometric sensitivity loss, and speech understanding: a case study. AB - The clinical measurement of otoacoustic emissions can assist in differentiating between peripheral and central explanations for deficits in speech understanding. We present audiometric and distortion-product emission data in a case with sensorineural hearing loss and a deficit in speech understanding. The presence of evoked emissions argues against attributing the speech audiometric loss to cochlear defect. PMID- 1421462 TI - High-frequency thresholds: sound suite versus hospital room. AB - Benefits of high-frequency audiometry in monitoring hearing sensitivity of patients administered ototoxic medications are well established. Thresholds obtained within a sound suite have been proven reliable. It may, however, often be necessary for the audiologist to evaluate the patient at bedside. The primary purpose of this study was to determine if significant differences are present between high-frequency thresholds measured in a sound suite versus thresholds measured in a hospital room. In addition, the test-retest reliability of high frequency thresholds was determined when measured in a hospital room. For 25 normal hearing subjects, results revealed that significant differences were not observed between thresholds measured in a sound suite versus those measured in a typical hospital room. In addition, differences between the initial and repeated thresholds obtained in the hospital room were not significant, and the differences were, for the most part, within +/- 10 dB at all test frequencies. PMID- 1421463 TI - Implications of audiologic success? PMID- 1421464 TI - Effects of interstimulus interval on slow phase velocity to ipsilateral warm air caloric stimulation in normal subjects. AB - This study investigated the effects of interstimulus interval on slow phase velocity (SPV) to ipsilateral warm air caloric stimulation in normal subjects. Results suggest that about 3 minutes should intervene between the offset of one irrigation and the onset of the second irrigation. This finding supports the hypothesis that carryover effects are likely only when nystagmus from the preceding irrigation overlaps the subsequent irrigation. If correct, clinicians do not have to wait a fixed time period between stimuli, but can initiate caloric stimulation as soon as nystagmus has ceased from the preceding irrigation. This recommendation compensates for individual and procedural differences. Test-retest reliability also was investigated. Findings suggest that when immediate test retest differences exceed approximately 6 degrees/second (95% confidence interval), the examiner should administer additional trials until stability is ascertained. Moreover, unusual or significant findings should be verified with repeat testing. PMID- 1421465 TI - SPIN test performance of elderly hearing-impaired listeners. AB - Normative information is available on the expected performance of hearing impaired individuals on the revised version of the Speech Perception in Noise (SPIN) test. This normative sample includes individuals with sensorineural hearing loss drawn from an age range of 19 to 69 years, with 79 percent of the sample being less than 65 years of age. In the present study, SPIN scores were obtained from both ears of 98 elderly, hearing-impaired listeners (age range: 60 to 78 years). When the percent-correct scores on the High-Predictability (PH) items and on the Low-Predictability (PL) items are viewed as two separate measures, mean performance of the current "elderly-only" sample is similar to the performance of the original normative sample. However, for a certain percentage (18%) of the aged ears, the contextual cues provided in the PH sentences were not used as effectively as expected based on the normative guidelines. PMID- 1421466 TI - Responses of elderly hearing aid users on the hearing aid performance inventory. AB - The responses of hearing aid users aged 65 to 80 years to a 64-item measure of perceived benefit afforded by hearing aids were collected in order to develop normative data concerning the perceived benefit afforded specifically to elderly patients. Across most of the listening situations evaluated, the elderly respondents reported less perceived benefit than the generally younger listeners from the original normative study for this measure. For the current respondents, perceived hearing aid benefit was not related to variables such as average hearing loss, hearing aid style, or length of hearing aid use, but was related to hours per week of hearing aid use. A shortened version of this questionnaire is proposed, which uses just those questions most likely to be answered by elderly respondents. PMID- 1421467 TI - Comparison of Etymotic insert and TDH supra-aural earphones in auditory brainstem response measurement. AB - There are few systematic comparisons of Etymotic ER-3A insert earphones versus supra-aural earphones in auditory brainstem response (ABR) measurement. We compared ER-3A insert earphones and two types of supra-aural earphones (TDH-39P and TDH-49P) in a group of normal hearing adults. Acoustic analyses revealed spectral and temporal differences among earphones. Behavioral and ABR thresholds to click stimuli were slightly elevated with the ER-3A compared to the TDH earphones. The ER-3A earphones produced a latency delay, relative to the TDH earphones, that varied from about 0.8 to 1.0 msec, and increased at lower stimulus intensity levels. In addition, ABR wave I amplitude was significantly reduced with the ER-3A earphone. Based on these data, we recommend collection of normative data with the ER-3A earphones prior to their use in ABR measurement. PMID- 1421468 TI - Effects of cochlear hearing loss on the ABR latencies to clicks and 1000 Hz tone pips. AB - High-frequency hearing losses can substantially confound the interpretation of click-evoked auditory brainstem responses (ABRs). One method proposed to circumvent the problem is to use frequency-specific tone pips to stimulate equivalent areas on the basilar membrane in normal and pathologic groups, or in both ears of asymmetrically impaired patients. This retrospective study investigated the ABRs to clicks and 1000-Hz tone pips from 90 asymmetrically impaired subjects with cochlear pathology. The 4000 Hz threshold significantly affected the wave V latencies from both clicks and tone pips for the most severely impaired subjects. The wave V latencies were highly correlated between ears for both stimuli, but the correlation was higher with the 1000-Hz tone pips. It was concluded that the use of 1000-Hz tone pips can supplement the interpretation of click-evoked ABRs, particularly in patients whose 2000- and/or 4000-Hz thresholds are worse than 75 dB HL. PMID- 1421469 TI - Evaluation of prescriptive fitting. AB - The purpose of this study was to determine the minimum tolerance needed when choosing a manufacturer who custom-built analog circuitry for all-in-the-ear hearing aids to match a popular prescriptive amplification formula. Given the tolerance, a second purpose was to evaluate fitting success by calculating the differences in prescribed versus preferred gain and pre- versus postfitting perceived benefits. Eight elderly adults with mild to moderate sensorineural hearing losses participated. Real ear measurements were obtained via a probe-tube microphone system. Even when providing for the optimal scenario of custom building the circuitry, the inherent limitations of analog technology allowed no better than a +/- 12 dB electroacoustic match to prescribed gain. Although the minimum tolerance found was less than previous studies, it was still considered excessive given the differences in prescribed gain among formulae. Regardless of the large tolerance and a preference for less gain than prescribed, the subjects reported substantial benefit with the fitting approach. PMID- 1421470 TI - Evaluation of the efficacy of a multimemory hearing aid. AB - Although multimemory hearing aids have theoretical advantages over conventional "single memory" hearing aids, research and clinical data are not available to support their efficacy. The present study reports on the usefulness of a commercially available multimemory hearing aid in daily listening situations. Nineteen elderly hearing-aid wearers were fitted with the Quattro Q8 hearing aid. A modified Simplex procedure was used to select the electroacoustic characteristics for each memory. Subjects wore the device home and reported their satisfaction with each memory on the hearing aid in different listening situations. Their impressions on the whole hearing aid and on the remote feature were also sampled. Although a majority of subjects showed preference for multimemory design, such observations may not be readily evident until after extended use of the device. Inconvenience and cost of the device may prohibit some hearing-impaired listeners from using the device. PMID- 1421471 TI - Auditory brainstem response to tone bursts in quiet, notch noise, highpass noise, and broadband noise. AB - This study investigated the effects of tone bursts (1000 Hz, 2000 Hz, and 4000 Hz) in quiet, notch noise, highpass noise, and broadband noise on the identifiability, latency, and amplitude of the auditory brainstem response (wave V). Normal listeners were presented with 40 dB and 80 dB nHL tone bursts having rise-plateau-fall times of 1 msec. Wave V was observed in all subjects at 40 dB and 80 dB nHL for the quiet and noise conditions. The latency findings suggest that responses elicited by the 80 dB nHL tone bursts in quiet were, in part, mediated by regions on the basilar membrane that did not correspond to the center frequency of the tone burst. To increase frequency-specificity, high-level tone bursts (e.g., 80 dB nHL) should be mixed with notch, highpass, or broadband noise. The use of noise conditions for low intensity levels (e.g., 40 dB nHL) does not appear necessary for isolating the response because both the notch and the highpass conditions yielded latencies similar to the quiet condition. Although similar wave V amplitudes were found at all frequencies, amplitudes were smaller for the broadband noise than for the quiet, notch, and highpass conditions. Thus, the latter conditions seem preferred. PMID- 1421472 TI - Asymmetries in topographic brain maps of auditory evoked potentials in the elderly. AB - We compared topographic brain maps of the middle response (MR) and late response (LR) auditory evoked potentials in two groups of elderly males. Subjects were categorized on the basis of the performance of the poorer hearing ear on the Synthetic Sentence Identification (SSI) test. Evoked potentials, obtained in response to 1000-Hz tone pips and tone bursts, were recorded under three conditions of sound stimulation:binaural (BIN), left ear only (LE), and right ear only (RE). Comparisons of the topographic brain maps generated by the two groups revealed significant asymmetry in the MR of the experimental group. LE stimulation produced a larger response over the right hemisphere, and RE stimulation produced a larger response over the left hemisphere. This asymmetry was not observed in the experimental group with binaural stimulation, or in the control group in any of the three stimulation conditions. An analogous asymmetry was not recognized in the LR in either group for any of the three sound conditions. Results are interpreted in relation to the recently proposed model of multiple middle latency generators. PMID- 1421473 TI - The statistical analysis of circadian phase and amplitude in constant-routine core-temperature data. AB - Accurate estimation of the phases and amplitude of the endogenous circadian pacemaker from constant-routine core-temperature series is crucial for making inferences about the properties of the human biological clock from data collected under this protocol. This paper presents a set of statistical methods based on a harmonic-regression-plus-correlated-noise model for estimating the phases and the amplitude of the endogenous circadian pacemaker from constant-routine core temperature data. The methods include a Bayesian Monte Carlo procedure for computing the uncertainty in these circadian functions. We illustrate the techniques with a detailed study of a single subject's core-temperature series and describe their relationship to other statistical methods for circadian data analysis. In our laboratory, these methods have been successfully used to analyze more than 300 constant routines and provide a highly reliable means of extracting phase and amplitude information from core-temperature data. PMID- 1421474 TI - Ontogeny of the circadian system controlling release of sperm from the insect testis. AB - In the gypsy moth, the release of sperm bundles from the testis into the vas deferens is rhythmic and is controlled by a circadian pacemaker located in the reproductive system. However, in males kept since pupation in constant darkness (DD) and temperature, the release of sperm was arrhythmic. The release of sperm became rhythmic when males were transferred from a light-dark cycle (LD 16:8) to DD 6-7 days after pupation. To further investigate the development of the circadian system during the pupal stage, we exposed DD pupae to a single 8-hr pulse of light or 8-hr pulse of a 4 degrees C temperature increase on different days after pupation. The pattern of sperm release was determined 5-6 days after the pulse. Males that were exposed to light or temperature pulses 5 days after pupation subsequently showed nonrhythmic sperm release. However, about half of the pupae that received the pulse on day 6 and most of the pupae that received it on day 7 subsequently showed synchronized sperm release. These results suggested that the clock underlying rhythmic release of sperm becomes operational at approximately 6 days after pupation--that is, 2 days prior to initiation of rhythmic sperm release from the testis. PMID- 1421476 TI - Phase resetting of the Neurospora crassa circadian oscillator: effects of inositol depletion on sensitivity to light. AB - The input pathway between the blue-light photoreceptor and the circadian oscillator of Neurospora crassa has not yet been identified. To test the hypothesis that an inositol phospholipid signaling system might be involved in blue-light signal transduction, phase resetting by light was assayed in the inositol-requiring inl strain under conditions of inositol depletion. Phase resetting curves and dose-response curves indicated that cultures maintained on low inositol (25 microM) were several orders of magnitude more sensitive to light than those maintained on high inositol (250 microM). This difference in light sensitivity was a property of inositol auxotrophy and was not seen in the wild type or in an inositol-independent inl+ revertant. Phase resetting by temperature was not affected by inositol depletion, indicating that the effect on light resetting is specific to the light input pathway and is not the result of a change in the amplitude of the oscillator itself. The results indicate an indirect role for inositol metabolites in the light input pathway--one that is not likely to involve direct participation of an inositol phospholipid signal transduction mechanism. PMID- 1421475 TI - Properties of mutual coupling between the two circadian pacemakers in the eyes of the mollusc Bulla gouldiana. AB - We examined, in vitro, the effects of changing the free-running period (tau) of one oscillator on the phase relationship between the circadian rhythms of impulse activity in the optic nerves that are driven by the bilaterally paired ocular pacemakers in Bulla gouldiana. One eye of the coupled pair was treated either with lithium artificial seawater (to lengthen tau) or with low-chloride artificial seawater (to shorten tau). The results suggested that the coupling is relatively weak, since the majority (9 to 16) of eyes were unable to maintain a stable phase relationship when tau differences between the eyes were only about 1 hr. When stable phase differences were achieved, the tau of the coupled system was intermediate between the tau's of the individual oscillators, and the eye with the shorter intrinsic tau would invariably phase-lead the pair. Interestingly, in a few instances, pairs of eyes that had desynchronized by 9.5 10.5 hr resynchronized within a single cycle via a massive phase advance in the rhythm from the phase-lagging eye. The result suggests the existence of a novel phase-shifting mechanism that is part of the mutual coupling pathway. We found evidence that connection of the eye with the cerebral ganglion increases the tau of the ocular pacemaker, suggesting that efferent signals from the central nervous system influence tau. These signals may also modulate the phase-shifting response. PMID- 1421477 TI - Technical comment: ten-minute delay on dataquest actograms. PMID- 1421478 TI - Responses of female New World screwworm flies, Cochliomyia hominivorax, to coloured targets in the laboratory. AB - The responses of unmated female New World screwworm flies, Cochliomyia hominivorax Coquerel, to visual targets were studied in a wind-tunnel. Both activity and frequency of contacts with targets increased greatly when the screwworm attractant mixture swormlure-4 was added to the airstream. Target orientated responses depended on target colour, with red and black targets being preferred over blue, white and yellow ones; this preference was much greater in the presence of odour than in its absence. No preference was detected for different shapes and orientations of red targets, all of equivalent surface area. Omitting different components from swormlure-4 generally resulted in a large reduction in activation and target contacts. Attempts to substitute 1-octen-3-ol for the butanol fraction were unsuccessful, but skatole may substitute to some extent for indole; the two isomers of butanol normally present in swormlure-4 may substitute partly or completely for each other. This type of measurement forms a suitable bioassay in the development of attractive targets for monitoring and control of wild adult screwworm populations. PMID- 1421479 TI - A generalized approach to detection of organophosphate resistance in mosquitoes. AB - Insecticide bioassays and biochemical microtitre assays were compared for detection of resistance to the organophosphate insecticides malathion and fenitrothion, using inbred laboratory strains of malaria vectors Anopheles albimanus Wiedemann, An.arabiensis Patton and An.stephensi Liston. With susceptible mosquitoes, the LT100 values determined from bioassays corresponded closely with times taken to abolish the activity of acetylcholinesterase activity in biochemical assays: approximately 2 h for malathion and 3 h for fenitrothion. Resistant strains of all three anophelines showed longer survival correlated with prolonged acetylcholinesterase activity. An.albimanus strains with insensitive acetylcholinesterase survived bioassays with discriminating doses of 1 h exposure to 5% malathion or 1% fenitrothion and were judged as resistant. It is concluded that enzyme-specific microassays provide a reliable means of detecting resistant individuals, with practical advantages over bioassays which do not reveal the resistance mechanism and require large numbers of healthy mosquitoes. PMID- 1421480 TI - Studies on vectors of Trypanosoma cruzi in Trinidad, West Indies. AB - Studies on vectors of Trypanosoma cruzi Chagas were conducted during 1982-85 as part of an investigation on the epidemiological status of American Trypanosomiasis in Trinidad, West Indies. A total of 148 reduviid bugs were collected from caves, armadillo nests and at light traps, comprising four sylvatic species and totalling 120 Panstrongylus geniculatus (Latreille), two P. rufotuberculatus (Champion), twelve Rhodnius pictipes Stal and fourteen Eratyrus mucronatus Stal. A significantly higher level of infection with T. cruzi was recorded for P. geniculatus (42.5%) compared to R. pictipes (8.3%). The other two bug species were not found to be infected. P. geniculatus seems to be the most important vector in the sylvatic cycle of transmission of T. cruzi in Trinidad. PMID- 1421481 TI - Effect of puparia incubation temperature: increased infection rates of Trypanosoma congolense in Glossina morsitans centralis, G. fuscipes fuscipes and G. brevipalpis. AB - Puparia of Glossina morsitans centralis (Machado), G.fuscipes fuscipes (Newstead) and G.brevipalpis (Newstead) were incubated at 25 +/- 1 degrees C, 28 +/- 1:25 +/ 1 degrees C, day:night or 29 +/- 1 degrees C throughout the puparial period, and maintained at 70-80% relative humidity. Puparial mortality was higher at 29 than at 25 degrees C (optimum temperature) in all three species, particularly in G.f.fuscipes and G.brevipalpis. Adults of G.m.centralis from puparia incubated at 29 degrees C, and those of this subspecies, G.f.fuscipes and G.brevipalpis from puparia incubated at 28:25 degrees C, day:night or 25 degrees C throughout, were infected as tenerals (27 h old) by feeding them at the same time on goats infected with Trypanosoma congolense (Broden) IL 1180 after the parasites were detected in the wet blood film. Infection rates on day 25 post-infected feed were higher in G.m.centralis from puparia incubated at 29 degrees C and in adults of the three different tsetse species from puparia incubated at 28:25 degrees C, day:night, than in those from puparia incubated at 25 degrees C. However, in G.f.fuscipes the labral and hypopharyngeal infection rates were not significantly different from those of the tsetse produced by puparia kept at 25 degrees C. PMID- 1421482 TI - Chemical control of Ornithonyssus sylviarum on caged layer hens. AB - Manual application of aqueous solutions of malathion, carbaryl and permethrin controlled northern fowl mite, Ornithonyssus sylviarum Canestrini and Fanzago, on caged layer hens for at least 118 days. Azamethiphos sprayed manually provided acceptable control for a shorter period. Machine application, particularly of azamethiphos, but also malathion, provided lesser control. The addition of surfactant increased the wetting ability of the sprays but interfered with the efficacy of azamethiphos. PMID- 1421484 TI - Cytotaxonomic confirmation of two forms of Simulium sirbanum in the eastern part of the Onchocerciasis Control Programme in West Africa. AB - An earlier report (Cheke et al., 1987) of morphological differences between populations of Simulium sirbanum Vajime & Dunbar in West Africa was confirmed cytotaxonomically. Populations with adult males having Type III scutal patterns were associated with male larvae heterozygous for the inversion IS-3, whereas adult males with Type IV scutal patterns were associated with larvae homozygous for IS-3. The taxonomic implications are briefly discussed but the evidence is considered to be inappropriate for resurrecting S. sudanense Vajime & Dunbar. Aspects of the biology of the two forms and their importance in onchocerciasis transmission are discussed. PMID- 1421483 TI - Anopheles nili as the main vector of human malaria in villages of southern Cameroon. AB - In villages near Sanaga river, in the forest zone of south Cameroon, Anopheles nili Theobald is the main species of mosquito regularly found biting man inside houses. Its densities are related to the flow level of the river. It is also the main malaria vector in terms of intensity and seasonal duration of transmission. The yearly malaria inoculation rate due to An. nili alone is 104 infective bites/man, varying between 3 infective bites/man in October and 20 in March. Anopheles gambiae Giles is a less important vector in the area but reached its peak in the dry season, when the Sanaga river is at its lowest level. These observations underline the influence of local ecology on malaria transmission and the need for entomological studies in each situation. PMID- 1421485 TI - Distribution and seasonality of Culex (Melanoconion) caudelli, a vector of arboviruses in Trinidad. AB - Seasonal and spatial distributions of the arbovirus vector mosquito Culex (Melanoconion) caudelli Dyar and Knab (Diptera: Culicidae) in the Aripo Wallerfield forest, Trinidad, were studied by collecting mosquitoes attracted to mouse-baited traps in forest, ecotone and savannah, one day per week throughout the year, 98% of the Cx caudelli mosquitoes were collected during the wet season, with a significant positive correlation between rainfall and mosquito catch. The reverse occurred during the dry season. Cx caudelli displayed a preference for the ecotone where 67% were collected, while 32% and 1% were collected in the forest and savannah respectively. PMID- 1421486 TI - Evidence for activation of endogenous opioid systems in mice following short exposure to stable flies. AB - Biting flies influence both physiology and behaviour of domestic and wild animals. This study demonstrates that brief (30 min) exposure of male and female mice to stable flies leads to significant increases in nociceptive responses, indicative of the induction of analgesia. The biting fly-induced analgesia was mediated by endogenous opioid systems as it was blocked by the prototypic opiate antagonist naloxone. Exposure for 30 min to the bedding of biting fly-exposed mice also induced significant opioid mediated analgesic responses in mice. Exposure to either house flies or the bedding of house fly-exposed mice had no significant effects on nociception. These results indicate that brief exposure to either stable flies, or to olfactory cues associated with mice exposed to stable flies, activates endogenous opioid systems leading to the induction of analgesia and likely other opioid mediated behavioural and physiological stress responses. These results suggest the involvement of endogenous opioid systems in the mediation of the behavioural and physiological consequences of biting fly exposure in domestic and wild animals. PMID- 1421487 TI - Borrelia burgdorferi infection in Ixodes ricinus from habitats in Denmark. AB - A total of 2647 ticks of the genus Ixodes was sampled by flagging the vegetation in thirty-one sites in eastern Jutland, Denmark. All ticks were identified as Ixodes ricinus Linnaeus. A total of 317 ticks (202 nymphs and 115 adults) from three different sites were examined for the spirochaete Borrelia burgdorferi Johnson et al. by indirect fluorescent antibody staining; the frequency of infection varied from 7% to 22%. It is concluded that I. ricinus, known to be the most common tick in Denmark, is the vector largely responsible for the transmission of B. burgdorferi in this country. PMID- 1421488 TI - Colonization of the mouse cadaver by flies in southern England. PMID- 1421489 TI - Lack of outer caudal setae as a constant feature of Phlebotomus tobbi larvae. PMID- 1421490 TI - Field and laboratory evidence for multiple bloodfeeding by Lutzomyia longipalpis (Diptera: Psychodidae). PMID- 1421491 TI - An analysis of supernumerary or B-chromosomes of wild and laboratory strains of Glossina morsitans morsitans. PMID- 1421492 TI - Blowfly species composition in sheep myiasis in Britain. PMID- 1421493 TI - Metabolic heat generation in dipteran larval aggregations: a consideration for forensic entomology. PMID- 1421494 TI - Population dynamics and control of Triatoma infestans. AB - Analysis of field populations of Triatoma infestans (Hemiptera: Reduviidae), after a 3-year study, shows that population growth rate is affected by both density-dependent and density-independent mortality. Although an equilibrium exists, apparently as a consequence of a density dependent-mechanism, population density fluctuates throughout the year because of the effect of monthly mean minimum temperature as a density-independent source of mortality. Simulation studies based on Moran curves shows that high population densities have an approximately constant extinction probability (around 0.20), independently of the season the population starts growing. However, at very low population densities, the extinction probability depends strongly on the season when the population begins to grow. Very low density populations beginning in winter or autumn have the highest extinction probability. The outcome of the simulation studies coincides with results observed in field populations affected by insecticide application at different seasons. PMID- 1421495 TI - Responses of female New World screwworm flies, Cochliomyia hominivorax, to swormlure-4 in the laboratory. AB - The behaviour of 4-day-old virgin female New World screwworm flies Cochliomyia hominivorax Coquerel was investigated in a wind tunnel using video. Addition of the screwworm attractant swormlure-4 to the airstream resulted in an increase in the number of take-offs and in the duration of flight. In the presence of swormlure-4 the flight speed decreased and the rate of turning increased. Take off was significantly orientated upwind during the period when swormlure-4 was added to the airstream, and significantly orientated downwind in the period after the addition of swormlure-4. The possible means by which this species finds a point source of odour in the field are discussed and compared with the mechanisms used by other flies. PMID- 1421496 TI - Snail predation by larvae of Sepedon scapularis Adams (Diptera: Sciomyzidae), a potential biocontrol agent of snail intermediate hosts of schistosomiasis in South Africa. AB - Malacophagous larvae of the fly Sepedon scapularis Adams were shown experimentally to be effective predators of three species of aquatic pulmonate snails tested as prey: Bulinus africanus (Krauss) an important intermediate host of Schistosoma haematobium (Bilharz), Bulinus tropicus (Krauss) and the invasive species Physa acuta Draparnaud. Survival of S. scapularis larvae from instar to instar was negatively affected by the size of prey snails, since larvae tended to be asphyxiated by the mucous secretions of the snails, or by the larval hydrofuge hairs becoming entangled in snail faeces. In experiments to test the choice of S.scapularis larvae for different species and sizes of snails, B.africanus was significantly disfavoured compared with the other two snail species. Small snails (< 3 mm) were more frequently killed by all three larval instars of S.scapularis. First instars killed few, if any, large snails (> 7 mm), whereas second and third instars preyed effectively on all sizes of snails. Third instars killed significantly more snails than younger instars. For larvae offered only one species of snail as prey, the mean total number of snails killed per larva during its entire development was 49 B.africanus, 45 B.tropicus or 34 P.acuta. It is concluded that S.scapularis is potentially useful as a biological control agent for use against indigenous Bulinus and exotic Physa snails. PMID- 1421497 TI - Patterns of sandfly distribution in tropical forest: a causal hypothesis. AB - 1. In tropical rain forest, phlebotomine sandflies (Diptera: Psychodidae), such as Lutzomyia vespertilionis and L.ylephiletor, have an aggregated distribution on their tree buttress diurnal resting sites, as studied during 1987-88 at Finca la Selva in the Caribbean lowlands of Costa Rica. 2. Experimental transfer of flies to trees not used as resting sites indicated that many apparently suitable sites remain unoccupied. 3. Observations of sandflies on the buttresses revealed that males and females are juxtaposed more frequently than expected by chance alone. Courtship behaviour by three of the four species of sandfly studied was observed on the buttresses. 4. It is suggested that the use of buttresses as swarming sites for mating behaviour is more likely to account for the observed distribution patterns of sandflies than their use of buttresses simply as diurnal resting sites. PMID- 1421498 TI - Host preferences of the phlebotomine sandfly Lutzomyia longipalpis in Amazonian Brazil. AB - Experiments were undertaken to determine the relative attractiveness of humans, dogs and chickens to Lutzomyia longipalpis, the principal vector of Leishmania chagasi causing American visceral leishmaniasis. Field experiments in two villages on Marajo Island, Para State, Brazil, showed that one boy attracted significantly more flies than one dog or chicken, and slightly fewer flies than a group of six chickens. Experiments with laboratory-bred female flies showed that a significantly greater number of flies engorged on a single human than on either a single dog or chicken, and man-biting catches demonstrated the willingness of flies to bite in the field. It appears that Lu.longipalpis has catholic feeding habits, the attractiveness of different hosts being largely a function of their relative sizes. These results are discussed with reference to the epidemiology of visceral leishmaniasis in Brazil. PMID- 1421499 TI - Ootaxonomy and eggshell ultrastructure of Phlebotomus sandflies. AB - The eggshell structure of four sandfly species: Phlebotomus perniciosus Newstead, P.perfiliewi Parrot, P.papatasi Scopoli and P.duboscqi Neveu-Lemaire, was examined by scanning and transmission electron microscopy (SEM and TEM). At the TEM level, the eggshell appears to have a homogeneous vitelline envelope and a thick chorion. At SEM level, the eggshell of all species is characterized by the outer chorion forming a series of fifteen to twenty longitudinal sinuous ridges, cross-linked in places to form a pattern of polygons, each line of the chorion consisting of columns arranged in a palisade. The aeropyle region of the egg is described for the first time in phlebotomine sandflies. Specific characters of the eggshell topography are described for distinguishing between these and other species of Phlebotomus. PMID- 1421500 TI - Crossing type variability associated with cytoplasmic incompatibility in Australian populations of the mosquito Culex quinquefasciatus Say. AB - An analysis of cytoplasmic crossing type variation in Australian populations of Culex quinquefasciatus, a member of the Culex pipiens complex of mosquitoes, revealed high levels of variability causing partial incompatibility between natural populations. Segregating crossing types were commonly found together within sampled sites. No correlation was evident between similarity of crossing type and environmental parameters of the sites, nor distance between sites. The nature of the observed variation did not support the hypothesis of paternally expressed nuclear 'restorer' genes. Such high levels of crossing type variation would be likely to impede attempts to control populations of the Culex pipiens complex using cytoplasmic incompatibility. PMID- 1421501 TI - Carbohydrate-binding specificities of anti-erythrocyte lectins (haemagglutinins) in Anopheles gambiae gut extracts and haemolymph. AB - Lectins that agglutinate red blood cells (RBC) were demonstrated in Anopheles gambiae mosquito haemolymph and gut extracts. No apparent differences in haemagglutinin titres were detected between male and female mosquitoes and overall agglutinin levels were not increased following a bloodmeal. Titres were highest in the haemolymph and midgut extracts versus human AB, horse, chicken and goat RBCs and in hindgut against human AB, chicken and sheep; foregut extract gave relatively low titres. Adsorption of haemolymph and gut extracts with selected RBCs coupled with carbohydrate inhibition and the use of enzyme-treated RBCs revealed the presence of multiple (hetero-) agglutinins. An.gambiae lectins were specific for (1-1)-, (1-4)- or (1-6)-linked glucose based disaccharides, glucose and its (1-2) or (1-3) linkages with fructose and, to a lesser extent, aminated or N-acetylated glucose, or galactose and its deoxy derivatives. This study presents the first report of the occurrence of heterogenous anti-RBC agglutinins in haemolymph and gut extracts of the mosquito An.gambiae, together with the sugar-binding specificities of these lectins. PMID- 1421502 TI - A comparison of African buffalo, N'Dama and Boran cattle as reservoirs of Trypanosoma congolense for different Glossina species. AB - Teneral Glossina morsitans centralis Machado were fed on the flanks of the African buffalo (Syncerus caffer Sparrman), N'Dama (Bos taurus L.) or Boran (Bos indicus L.) cattle infected with Trypanosoma congolense Broden. The infected tsetse were maintained on rabbits and on day 30 after the infected feed, the surviving tsetse were dissected to determine the infection rates. The mean infection rates (% +/- SE) in the midgut of tsetse fed on buffalo, N'Damas and Borans were 23.5 +/- 3.3, 31.6 +/- 2.7 and 33.7 +/- 4.6, respectively. The differences were not significant. However, the mean mature infection rate in tsetse fed on the buffalo (13.2 +/- 2.1%) was significantly lower compared to the rates in tsetse fed on the N'Dama (20.4 +/- 1.4) or the Boran cattle (21.4 +/- 1.1). When groups of teneral G.m.centralis, G.pallidipes Austen, G.p.gambiensis Vanderplank, G.f.fuscipes Newstead, G.brevipalpis Newstead and G.longipennis Corti were fed simultaneously on either an infected buffalo, an N'Dama or a Boran steer, the mature infection rates ranged from 0 to 16.1%. Irrespective of the host species used, the T.congolense infection rate was highest in G.m.centralis, lowest in the palpalis and fusca group tsetse, with G.pallidipes being intermediate. Nevertheless, the trypanoresistant African buffalo and N'Dama may serve as reservoirs of T.congolense as can trypanosusceptible Boran cattle. PMID- 1421503 TI - Modelling the effect of feeding-related mortality on the feeding strategy of tsetse (Diptera: Glossinidae). AB - Free-living haematophagous insects risk death through host grooming responses or through increased susceptibility to predation whenever they take a bloodmeal. In this paper we investigate the effects of these risks on the feeding strategy of tsetse. A model is presented that allows for death of tsetse by starvation if they do not succeed in feeding within a fixed time (set at 6 days in the first instance) and for mortality specifically associated with feeding. In addition there is background mortality that applies to all flies at all times. The model is used to compute the individual life-time fertility (number of female puparia per female) as a function of the probability of obtaining a meal (indicated by field data to be very high, usually > 0.85 per day) and the day on which flies start to search for a meal. We suggest that the feeding strategy that would be selected for is that which allows the maximum reproductive output. The model shows that this strategy involves making no attempts to feed for 3-4 days after the previous meal and then attempting to feed with the greatest possible probability until a meal is obtained. The predicted feeding interval, obtained independently of any trapping data, agrees closely with all previous estimates from field studies using a variety of methods. Preliminary results from a laboratory experiment reveal an increased risk of predation of recently fed as compared with hungry tsetse. The lower the actual feeding mortality the more frequently will flies be able to feed should conditions so demand. It is adaptive, however, for tsetse to delay attempting to feed for as long as they can, which is made possible by the near certainty of locating and feeding on a host within 1 day, using their sophisticated sensory systems. PMID- 1421504 TI - Effects of hydroprene on development and reproduction in the Oriental cockroach, Blatta orientalis. AB - Nymphs of the Oriental cockroach Blatta orientalis were exposed during the penultimate and final instars to vinyl tiles treated with the juvenile hormone analogue hydroprene. Adults moulting from these nymphs exhibited deformities such as twisted wings in both sexes and modified genitalia in females. Females with deformities were unable to produce viable oothecae. B.orientalis confined on tiles treated with hydroprene at rates of 25-100 mg/m2 did not reproduce. The treatment rate of 10 mg/m2 reduced fecundity and caused 47-57% of resultant adults to have deformities, but some adults reproduced successfully and population growth was not suppressed. PMID- 1421505 TI - Acquired immunity to larvae of Amblyomma marmoreum and A.hebraeum by tortoises, guinea-pigs and guinea-fowl. AB - A study of acquired resistance in guinea-pigs, guinea-fowl and tortoises to larvae of the ticks Amblyomma hebraeum Koch and A.marmoreum Koch (Acari: Ixodidae) showed that repeated infestations of the laboratory host resulted in a 29.3-49.4% reduction respectively in weight of engorged larvae. No resistance was induced in guinea-fowl, the natural host for larvae of both species. A small decline in the mean weight of engorged larvae was observed for both species of ticks after three successive infestations on tortoises. The reduction in weight was more pronounced in A.hebraeum (14.5%) which does not naturally feed on tortoises than for A.marmoreum (8.4%), a common tick on this host. The occurrence of acquired resistance in natural tick host relationships as opposed to unnatural tick host relationships is discussed. PMID- 1421506 TI - Phoretic and parasitic mites infesting the New World screwworm fly, Cochliomyia hominivorax, following sterile insect releases in Libya. AB - During the screwworm eradication programme in Libya in 1991, trapped specimens of Cochliomyia hominivorax (Coquerel) were found infested with phoretic mites, Macrocheles muscaedomesticae (Scopoli), or parasitic mites, Trichotromidium muscarum (Riley). The possible sources of infestation and potential effects of mites on screwworm flies are discussed. PMID- 1421507 TI - Circadian variation in venom yield by the scorpion Heterometrus indus (De Geer). PMID- 1421508 TI - Effects of flavonoids released naturally from bean (Phaseolus vulgaris) on nodD regulated gene transcription in Rhizobium leguminosarum bv. phaseoli. AB - Nine flavonoid aglycones released from black bean (Phaseolus vulgaris 'PI165426CS') seeds and roots induced nodC::lacZ transcription in Rhizobium leguminosarum bv. phaseoli strains containing extra cloned copies of the regulatory genes nodD1, nodD2, or nodD3 from that biovar. Individual flavonoids generally induced highest levels of nodC::lacZ transcription (Imax) with extra copies of nodD2, and the concentration required for half-maximum induction (I50) was lowest with extra copies of nodD1 genes. One apparently unique feature of R. l. bv. phaseoli is that naturally released flavonoids with very diverse structures induce nod genes. For all three nodD genes, two compounds exuded from roots, genistein and naringenin, produced much higher levels of nodC::lacZ transcription than other flavonoids, but this fact was not explained by increased transcription of the nodD genes themselves. The remaining seven flavonoid aglycones showed reproducibly different capacities to induce nodC::lacZ transcription, but all were considerably less powerful inducers than genistein and naringenin in strains with extra copies of each of the nodD genes. Tests with glycosides of the nod-gene inducers showed that glycosides, which are normally released by bean, had lower I50 values than the corresponding aglycones with all nodD genes. Additive interactions observed between the strong nod-gene inducer genistein and the weak inducer eriodictyol remain to be explained at the molecular level. PMID- 1421509 TI - An Xanthomonas citri pathogenicity gene, pthA, pleiotropically encodes gratuitous avirulence on nonhosts. AB - The pathogenicity gene, pthA, of Xanthomonas citri is required to elicit symptoms of Asiatic citrus canker disease; introduction of pthA into Xanthomonas strains that are mildly pathogenic or opportunistic on citrus confers the ability to induce cankers on citrus (S. Swarup, R. De Feyter, R. H. Brlansky, and D. W. Gabriel, Phytopathology 81:802-809, 1991). The structure and the function of pthA in other xanthomonads and in X. citri were further investigated. When pthA was introduced into strains of X. phaseoli and X. campestris pv. malvacearum (neither pathogenic to citrus), the transconjugants remained nonpathogenic to citrus and elicited a hypersensitive response (HR) on their respective hosts, bean and cotton. In X. c. pv. malvacearum, pthA conferred cultivar-specific avirulence. Structurally, pthA is highly similar to avrBs3 and avrBsP from X. c. pv. vesicatoria and to avrB4, avrb6, avrb7, avrBIn, avrB101, and avrB102 from X. c. pv. malvacearum. Surprisingly, marker-exchanged pthA::Tn5-gusA mutant B21.2 of X. citri specifically lost the ability to induce the nonhost HR on bean, but retained the ability to induce the nonhost HR on cotton. The loss of the ability of B21.2 to elicit an HR on bean was restored by introduction of cloned pthA, indicating that the genetics of the nonhost HR may be the same as that found in homologous interactions involving specific avr genes. In contrast with expectations of homologous HR reactions, however, elimination of pthA function (resulting in loss of HR) did not result in water-soaking or even moderate levels of growth in planta of X. citri on bean; the nonhost HR, therefore, may not be responsible for the "resistance" of bean to X. citri and may not limit the host range of X. citri on bean. The pleiotropic avirulence function of pthA and the heterologous HR of bean to X. citri are both evidently gratuitous. PMID- 1421510 TI - Broad host range and promoter selection vectors for bacteria that interact with plants. AB - A plasmid vector, pGV910, and a derived cosmid, pRG930, have been constructed. Both contain the ColE1 and pVS1 origins of replication and are stably maintained in Escherichia coli, Agrobacterium tumefaciens, and Azorhizobium caulinodans ORS571. They are compatible with commonly used IncP cloning vectors, although pVS1 was classified as an IncP plasmid, unable to replicate in E. coli (Y. Itoh, J.M. Watson, D. Haas, and T. Leisinger, Plasmid 11:206-220, 1984). Promoter selection vectors were derived from both of these plasmids by using a promoterless beta-glucuronidase and/or beta-galactosidase gene. These vectors facilitate the study of gene expression in bacteria under particular environmental conditions. This is illustrated by the expression of the gusA gene under the control of a nod promoter in A. caulinodans nodulating stem-located infection sites on Sesbania rostrata. PMID- 1421511 TI - Isolation and gene disruption of the Tox5 gene encoding trichodiene synthase in Gibberella pulicaris. AB - The trichodiene synthase gene (Tox5) was isolated from Gibberella pulicaris, and its nucleotide sequence was determined. Tox5 was disrupted through transformation with a plasmid carrying a doubly truncated copy of the coding region and a selectable marker for resistance to hygromycin B (Hygr). Analysis of 82 transformants for their ability to produce the trichothecene, 4,15 diacetoxyscirpenol (DAS), resulted in the identification of five DAS- strains. Southern hybridization analysis of DAS- Hygr transformants indicated that the plasmid integrated at the Tox5 locus. The disrupted Tox5 gene was shown to be mitotically stable. Analysis of nine tetrads revealed either the cosegregation of the disrupter plasmid and the DAS- phenotype or the loss of the disrupter plasmid. These results demonstrate the feasibility of using gene disruption in G. pulicaris and suggest a general method for obtaining Tox5- mutants in other trichothecene-producing fungi. PMID- 1421512 TI - Structural and functional analysis of two different nodD genes in Bradyrhizobium japonicum USDA110. AB - Bradyrhizobium japonicum has two closely linked homologs of the nodulation regulatory gene, nodD; these homologs are located upstream of and in divergent orientation to the nodYABCSUIJ gene cluster. We report here the nucleotide sequence and mutational analyses of both nodD copies. The predicted NodD1 and NodD2 proteins shared 62% identical amino acid residues at corresponding positions and exhibited different degrees of homology with NodD proteins of other Bradyrhizobium, Azorhizobium, and Rhizobium strains. Induction of the nodYABCSUIJ operon, as measured by expression of a translational nodC'-'lacZ fusion, required the nodD1 gene, but not nodD2. A B. japonicum mutant deleted for both nodD copies (strain delta 1267) still showed residual nodulation activity; however, nodulation of soybean was significantly delayed, and nodulation of mung bean and siratro resulted in strongly reduced nodule numbers. Fully efficient nodulation of mung bean and siratro by strain delta 1267 was restored by genetic complementation with the nodD1 gene, but not with nodD2. We conclude from these data that nodD1 is the critical gene that contributes to maximal nodulation efficiency, whereas the nodD2 gene does not play any obvious role in nodulation of the host plants tested. PMID- 1421513 TI - Changes in the activity and the polypeptide composition of the oxygen-evolving complex in photosystem II of tobacco leaves infected with cucumber mosaic virus strain Y. AB - The amount of 22- and 23-kDa polypeptides in a 23-kDa protein family, which plays a regulatory role in photosynthetic oxygen evolution, decreased significantly during the progress of appearance of chlorotic spots in cucumber mosaic virus strain Y (CMV[Y])-inoculated tobacco (Nicotiana tabacum 'Ky57') leaves (Plant Mol. Biol. 16:689-698, 1991). The present study was conducted to determine if the amount of other polypeptides of the oxygen-evolving complex and the oxygen evolving activity also decreased in CMV(Y)-inoculated tobacco leaves. The amount of a 33-kDa polypeptide, which is essential to oxygen evolution, did not decrease in CMV(Y)-inoculated leaves showing early symptoms, although the amount of 22- and 23-kDa polypeptides began to decrease. However, comparative analysis of electron transport in thylakoid membranes indicated that the oxygen-evolving activity in CMV(Y)-inoculated tobacco leaves was only partly reduced, compared with the activity in CMV(O)-inoculated tobacco leaves which did not show clear symptoms. Partial inhibition of the oxygen-evolving activity, by a differential decrease in the amount of polypeptides of the oxygen-evolving complex, seems to be associated with the primary molecular process of symptom expression in CMV(Y) inoculated tobacco leaves. PMID- 1421514 TI - 252Cf plasma-desorption mass spectrometry of lipid A from Enterobacter agglomerans. AB - Endotoxins from gram-negative bacteria are believed to be causative agents of byssinosis, an occupational pulmonary disease associated with exposure to cotton dust in textile mills. Lipid A preparations from Enterobacter agglomerans, a gram negative bacterium commonly found in cotton and cotton dust, have been analyzed using plasma-desorption mass spectrometry. Results indicate the existence of at least two lipid A types which differ only by the presence of an additional oxygen atom whose position has been localized to the acyloxyacyl ester-linked side-chain of the distal portion of the molecule. The lower molecular weight compound of the two structures has the same molecular weight and presumably the same empirical formula as a well-characterized lipid A from Salmonella minnesota. The mass spectra of lipid A compounds obtained from S. minnesota and E. agglomerans show strong similarities. Palmitoyl, hydroxymyristoyl, myristoyl, and lauroyl side chains which are known to be present in the former are inferred from spectral evidence to be present in the latter. PMID- 1421515 TI - Mass spectrometry of DNA mixtures by laser ablation from frozen aqueous solution. AB - We report time-of-flight mass spectra of test mixtures of six single-stranded DNA segments. The segments range in size from 8 to 60 nucleotides (molecular weight range 2413 to 18,602 Da). The best mass spectra were obtained by pulsed laser ablation of thin frozen films of an aqueous solution of the mixture from an oxidized copper substrate. These mass spectra are dominated by the molecular-ion peak for each DNA segment, and show little evidence of fragmentation, peak broadening or cluster formation. In contrast, mass spectra obtained using UV laser ablation from an anthranilic acid matrix yield broad peaks with evidence of fragmentation, and DNA segments longer than 26 nucleotides are difficult to detect. PMID- 1421516 TI - Determination of 15N enrichment of taurine in cat urine by high resolution fast atom bombardment mass spectrometry. AB - A method is described for measuring the stable isotopic enrichment of taurine in cat urine samples by high resolution fast-atom bombardment mass spectrometry, after 15N labelled taurine was given to cats for the purpose of investigating taurine metabolism. The 15N enrichment of taurine was measured after hydrolysis and purification of taurine by anion/cation exchange chromatography. The isotopic ratio of taurine was determined by measuring the [M+H]+ ion peaks in the spectra of the unlabelled and labelled compounds under multiple ion scan conditions. The overall standard deviation of the measurement is better than 4%. This method requires no derivation and uses only 500 microL of urine samples. PMID- 1421517 TI - Expression of cell adhesion molecules during initiation and cessation of neural crest cell migration. AB - Because of their distribution and known ability to promote neuronal adhesion, it has been proposed that N-CAM and N-cadherin are involved in the formation of the nervous system. Here, we examine the expression of these molecules during the initiation and cessation of trunk neural crest cell migration during the formation of the peripheral nervous system. Whereas other neural tube cells express N-cadherin, the dorsal neural tube containing neural crest precursors has little or no N-cadherin immunoreactivity. In contrast, N-CAM is expressed in the dorsal neural tube and on early migrating neural crest cells, from which it gradually disappears during migration. Both N-CAM and N-cadherin are absent from neural crest cells at advanced stages of migration. As neural crest cells cease migration and condense to form dorsal root and sympathetic ganglia, N-cadherin but not N-CAM is observed on the forming ganglia, identified by neurofilament expression and the aggregation of HNK-1 reactive cells. The results demonstrate that the absence of N-cadherin correlates with the onset of neural crest migration and its reappearance correlates with cessation of migration and precedes gangliogenesis. PMID- 1421518 TI - Molecular analyses of carbonic anhydrase-II expression and regulation in the developing chicken lens. AB - The expression of carbonic anhydrase-II (CA-II) in the developing chicken lens was examined and compared with that in the retina of the chicken embryo. CA-II expression was measured by immunohistochemistry and radioimmunoassay during development, and CA-II mRNA was quantified by Northern blot and densitometric scanning and localized by in situ hybridization. A functional promoter of the chicken CA-II gene was identified by transfection of primary embryonic chicken lens epithelial cells and analyzed in deletion mutants. The results establish that CA-II makes up about 0.1% of the total soluble protein of the embryonic chicken lens, an amount insufficient to make it a candidate for an enzyme crystallin in this species. Lens fiber differentiation coincided with a loss of CA-II mRNA and protein; by contrast, CA-II persisted in the epithelial cells of the embryonic and mature lens. This and previous studies showed that CA-II amounts to as much as 3% of the protein of the embryonic chicken retina and follows a different developmental time course of expression; like the lens, CA-II decreases until day 10 in the embryonic retina, but, unlike the lens, it increases thereafter and plateaus at hatching. Progressive deletions of the 5' flanking regions (from position -1314 to +32) of the CA-II gene fused to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene resulted in a gradual loss of promoter activity, consistent with an additive effect of putative cis-regulatory elements found in many crystallin genes. These experiments provide the foundation for a molecular analysis of the developmental and differential regulation of the CA-II gene in lens and retina. PMID- 1421519 TI - Association interneurons of embryonic rat spinal cord transiently express the cell surface glycoprotein SNAP/TAG-1. AB - SNAP/TAG-1 is a 135 kDa glycoprotein of the immunoglobulin superfamily that is transiently expressed upon the surfaces of developing axons. In the embryonic rodent spinal cord, this molecule is expressed by motor neurons, dorsal root ganglion cells, and commissural neurons (Yamamoto et al.: J. Neurosci. 6:3576 3594, 1986; Dodd et al.: Neuron 1:105-116, 1988). The commissural cells are a subset of early-forming dorsal horn interneurons whose axons follow a circumferential course in the embryonic spinal cord. The axons of commissural neurons cross the developing ventral commissure to terminate on contralateral synaptic targets, whereas those of the other subset of circumferential cells, the association interneurons, remain on the same side of the spinal cord to form ipsilateral, terminal synaptic fields. The difference between the axonal trajectories of these two subsets of nerve cells raised the question of whether or not association interneurons would also express the SNAP/TAG-1 epitope and, if so, how would this expression be related to that of the commissural cells. Immunocytochemistry for SNAP/TAG-1 and choline acetyltransferase (ChAT) was used to answer these questions. The results indicated that association interneurons expressed SNAP/TAG-1 epitopes and that this expression began later and lasted longer than that of the commissural neurons. Other new findings of this study included the identification of a lateral subgroup of commissural fibers that expressed SNAP/TAG-1 later than their more medially located counterparts, and these lateral fibers were more pronounced in the thoracic spinal cord than at cervical levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421520 TI - Distinct regions of human fibronectin are essential for fibril assembly in an in vivo developing system. AB - In early vertebrate development, the proper assembly of fibronectin into fibrils is crucial for embryonic cells to adhere and to migrate on the extracellular matrix. The molecular mechanisms by which such a process occurs in vivo are poorly understood. In the amphibian embryo Pleurodeles waltl fibronectin fibrils appear first at the blastula stage. They form a fibrillar matrix on the basal surface of animal cells facing the blastocoel. Using competition and perturbation experiments with purified proteolytic fragments and domain-specific monoclonal antibodies, we demonstrate that at least three fibronectin sites are essential for assembly of fibronectin fibrils in the blastula of Pleurodeles waltl. Two sites, the RGDS sequence and the synergistic domain in the 10th type III repeat, are both involved in receptor recognition. A third site that spans the 9th type I and 1st type III homology sequences is also likely to participate in fibronectin fibronectin interactions. PMID- 1421521 TI - A cyclical, developmentally-regulated death phenomenon in a colonial urochordate. AB - Botryllus schlosseri is a colonial ascidian whose asexually derived, clonally modular systems of zooids exhibit developmental synchrony. The blastogenic cycle culminates in a phase of programmed cell and zooid death called takeover, in which all functional zooids die over a 30 hr period, and are replaced by a new generation of individuals. Because of the weekly recurrence and magnitude of visceral death in this model organism, we have begun to characterize the mechanisms that govern takeover. Here we describe a monoclonal antibody (B3F12.9) that recognizes a novel 57 Kd polypeptide (under reducing conditions) localized to the perivisceral extracellular matrix (PVEM) of buds and zooids, as well as blood cells of Botryllus by immunofluorescence and immunogold labeling of tissue sections. During their active feeding phase, zooids exhibited a uniform labeling pattern of PVEM along their anteroposterior (A-P) axis. At the onset of takeover (T = 3 hr), B3F12.9 immunostaining became diffuse or absent at the anterior end, which paralleled the axis of contraction of the dying zooid, whereas the posterior end retained its labeling integrity. During mid (T = 15 hr) to late (T = 28 hr) takeover, issue damage was extensive, large blood macrophages and other B3F12.9 immunoreactive blood cells invaded the peribranchial cavity, whereas PVEM labeling gradually disappeared along the entire A-P axis. These findings indicate that takeover is a dynamic process in which extracellular matrix breakdown proceeds in a polarized fashion, beginning at the anterior end of each zooid and gradually propagating toward the posterior end. PMID- 1421522 TI - Localization of type II collagen, long form alpha 1(IX) collagen, and short form alpha 1(IX) collagen transcripts in the developing chick notochord and axial skeleton. AB - In this study we compare, by in situ hybridization, the spatial and temporal expression patterns of transcripts of avian type II collagen and the long and short forms of the (alpha 1) chain of type IX collagen during the development of the notochord and axial skeleton. We observed type II collagen and short form type IX collagen transcripts in the developing (stage 25-28) nonchondrogenic notochord. Conversely, long form type IX transcripts were not detectable in the notochord or perinotochordal sheath. Interestingly, all three transcripts colocalized in the developing chondrogenic vertebrae of the axial skeleton as well as in the chondrocranium and Meckel's cartilage. The expression of the short form of type IX collagen in these regions was more restricted than that of the long form. This report provides additional support for a complex regulatory pathway of cartilage marker gene expression in chondrogenic vs. nonchondrogenic tissues during avian embryogenesis. PMID- 1421523 TI - Cardiac expression of polysialylated NCAM in the chicken embryo: correlation with the ventricular conduction system. AB - The neural cell adhesion molecule (NCAM) and its polysialic acid moeity (PSA) affect cellular interactions during the development of the nervous system and skeletal muscle. NCAM has also been identified in the embryonic heart of various species including humans. However, knowledge regarding the role of NCAM and its function-modulating PSA in cardiogenesis is limited. The distribution of NCAM and its PSA in the ventricular myocardium of chicken embryos was determined by indirect immunofluorescence staining. The NCAM polypeptide was found throughout the cardiac myocardium. In contrast PSA was located in discrete regions in stage 20 to 44 embryos (during and after septation). Myocardium at the subendocardial regions of the atrioventricular canal and ventricular trabeculae were PSA positive by stage 20. At later stages, transverse sections of the postseptation heart just below the level of the atrioventricular interface revealed a PSA positive bundle of myocardium in the septum. This bundle was continuous with two branches at a more apical level which in turn were continuous with the PSA positive subendocardial myocardium lining the left and right ventricles. This pattern of PSA in the myocardium was similar to that of the ventricular conduction system configuration defined in the adult heart. Electron micrographs of the subendocardium of the ventricular septum revealed PSA positivity on myofibril-containing cells with the ultrastructural location of Purkinje fibers. At later stages (35-44) a subset of cells within PSA-positive regions was stained by an antibody against an isoform of the myosin heavy chain found in adult Purkinje fibers. These cells and surrounding tissue lacked PSA in the adult heart. Thus polysialylated NCAM may be modulating cell-cell interactions during the development of the ventricular conduction system. PMID- 1421524 TI - Colonization of the developing pancreas by neural precursors from the bowel. AB - Neurons in ganglia of the myenteric plexus of the duodenum and stomach have recently been demonstrated to innervate pancreatic ganglia and transsynaptically to excite acinar and islet cells. The hypothesis that crest-derived cells first colonize the foregut and secondarily enter the pancreas by way of the pancreatic buds was tested. Studies were done with fetal rats (days E11-E15). Pancreatic rudiments and foregut were explanted separately and in co-culture. The development of neurons in the explants, identified by demonstrating the immunoreactivities of neurofilaments and growth-associated protein-43 (GAP-43), provided an indirect assay for the presence of neural precursors in the tissue at the time of explantation. Cells of putative neural crest origin were visualized immunocytochemically using the monoclonal antibody, NC-1. Additional markers included the immunoreactivities of dopamine-beta-hydroxylase (DBH), which is expressed by vagal crest-derived cells that colonize the bowel, neuropeptides (substance P and neuropeptide Y [NPY]) found in mature pancreatic neurons, and serotonin (5-HT), which is located in the cell bodies of enteric but not pancreatic neurons. Neurons were detected in cultures of foregut, but not pancreas, when these tissues were explanted by themselves at days E11 and E12. At E11 neural precursors did not leave explants of bowel or migrate into co-cultured pancreatic rudiments. When the foregut was explanted at E12, however, neural precursors migrated away from the bowel, giving rise both to distant ganglia and to neurons within co-cultured pancreatic rudiments. Intrapancreatic ganglia developed in the co-cultures even when the pancreatic attachment to the bowel was severed. Neurons appeared in pancreatic rudiments explanted by themselves on day E13. Neurons developing in pancreatic explants expressed the immunoreactivities of DBH, substance P, and NPY, but not 5-HT. These observations support the idea that pancreatic ganglia develop from crest-derived cells that first colonize the fetal rat foregut and there acquire the ability to colonize the pancreas. A later migration into the pancreatic rudiments of a subset of the original emigres or their progeny between days E12 and E13 gives rise to a network of pancreatic ganglia that can be regarded as an extension of the enteric nervous system. PMID- 1421525 TI - Adenosine levels in the postimplantation mouse uterus: quantitation by HPLC fluorometric detection and spatiotemporal regulation by 5'-nucleotidase and adenosine deaminase. AB - Extracellular adenosine has the potential to influence many aspects of target cell metabolism. The present study has determined the endogenous levels of adenosine in the pregnant mouse uterus and developing embryo-decidual unit with respect to the expression of two key enzymes of adenosine metabolism, 5' nucleotidase (5'-NT; EC 3.1.3.5) and adenosine deaminase (ADA; EC 3.5.4.4). To measure adenosine levels, nucleoside extracts were etheno-derivatized and quantitated by high-performance liquid chromatography-fluorescence detection (0.03 pmol/mg protein sensitivity). Adenosine levels were determined to be 0.18 nmol/mg protein in the nonpregnant uterus; however, two statistically significant changes were identified in the pregnant uterus: (1) a periimplantation surge between day 3 (0.24 nmol/mg protein) and day 5 (0.59 nmol/mg protein) of gestation (plug day 0; implantation day 4); and (2) an early postimplantation decline between day 6 (0.54 nmol/mg protein) and day 7 (0.10 nmol/mg protein). The periimplantation adenosine surge coincided with uterine expression of 5'-NT, an enzyme which catalyzes the irreversible dephosphorylation of 5'-AMP to adenosine. 5'-NT expression was shown by Northern blot analysis to peak in the embryo-decidual unit on day 5 of gestation and then to decline through day 9; transcripts remained elevated in the placenta between day 9 and day 13 (the latest day examined in this study). By use of specific enzyme histochemistry, most 5'-NT activity was localized to the primary decidual zone on day 5. This expression subsequently declined during regression of the primary decidua; however, 5'-NT appeared on giant trophoblast (days 7-13) and the metrial gland (days 11-13). Other purine catabolic enzymes degrading AMP (adenylate deaminase) or generating adenosine (S-adenosylhomocysteine hydrolase) were not detected in the embryo-decidual unit suggesting that the net flux of utero-placental AMP catabolism proceeds with adenosine as an intermediate, this being the major pathway of adenosine formation. The sharp drop in adenosine levels between day 6 and day 7 coincided with a rise in the activity and mRNA expression of ADA, an enzyme which catalyzes the irreversible deamination of adenosine to inosine. ADA was previously localized to the secondary decidual zone (days 6-11), secondary giant cells (days 7-13), and spongiotrophoblasts (days 8-13) in the mouse (Knudsen et al., 1991). Results of developmental Northern blot analysis demonstrated a direct correlation of relative 5'-NT/ADA mRNA band intensity to adenosine content between day 4 and day 9 of gestation, suggesting that the local availability of adenosine in the antimesometrium is dependent upon the distribution of these enzymatic activities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1421526 TI - Coincident loss of mitochondria and nuclei during lens fiber cell differentiation. AB - During normal differentiation, lens fiber cells lose their nuclei, mitochondria, and other membrane-bound organelles. In the present study, a slice preparation of the embryonic chicken lens was used with laser scanning confocal microscopy to study the spatial and temporal patterns of organelle breakdown during embryonic development. At all stages examined, mitochondria in lens epithelial cells were present in perinuclear clusters. In contrast, early in development, lens fiber cells contained extremely elongated mitochondria (> 100 microns) that were distributed throughout the cytoplasm and oriented along the long axis of the cells. By the 8th day of embryonic development (E8), the mitochondria in the central fiber cells began to fragment. At the same time, the nuclei in these cells became smaller and more spherical. By E10, mitochondrial staining in the central fibers became punctate. Electron microscopy of this region revealed swollen mitochondria with disrupted cristae. By E12, cells in the central region of the lens lacked mitochondria and nuclei. The loss of nuclei and mitochondria from a given cell was coincident and abrupt (2-4 hr), occurring in a previously unsuspected domain situated about 300 microns from the anterior surface of the lens. A cytoskeletal component, actin, persisted in the central cells indicating that organelle degradation represents a selective process and not simply the global degradation of supramolecular structures. Throughout embryonic development, the organelle-free region grew at approximately the same rate as the lens and, by the time of hatching, had expanded to match the diameter of the pupil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421527 TI - Expression of NCAM isoforms during skeletal myogenesis in the mouse embryo. AB - We have examined the developmental patterns of neural cell adhesion molecule (NCAM) gene expression in embryonic mouse skeletal muscle cells by in situ hybridization. Moreover, by utilising exon-specific cRNA probes, we have examined tissue specific splicing of the NCAM gene. We show that there is a distinct sequence of NCAM isoform expression during skeletal muscle development. Since NCAMs are also expressed in other cell types, particularly neurons, NCAM mRNAs have been colocalised with acetylcholine receptor alpha (AChR alpha) gene transcripts to identify muscle-specific expression. NCAM is first detected in somites as they first form, prior to their differentiation into muscle and nonmuscle compartments. Myotomes, the first skeletal muscle masses to form in the embryo, express mRNAs for the transmembrane 180 and 140 kDa isoforms of NCAM. Both of these transcripts are also detected in the neural tube, and their spatial pattern of expression changes with development. Transcripts containing the muscle specific domain (MSD) of the NCAM gene are not detected prior to 11 days postcoitum (p.c.), at a time when rostral somites already contain well-developed myotomes. As the level of MSD mRNAs increases at 12 days p.c., the 140 and 180 kDa transcript levels decrease in skeletal muscle masses. The level of all NCAM isoform transcripts declines between 13 and 15 days p.c. in muscle. However, the 180 and 140 kDa NCAM isoforms are expressed at a high level in neural tissue and in other locations in the developing embryo such as in smooth muscle, around vibrissae follicles, and in the perichondrial zone of digits. PMID- 1421528 TI - High-intensity nociceptive stimuli minimize behavioral effects induced by restraining stress during the tail-flick test. AB - Analgesia following exposure to various stressors is a well-documented phenomenon. Restraint of an animal during the tail-flick test (TFT) represents a potent stressor that can induce both altered baseline latencies and enhanced response to opioids. The present study shows that the use of higher stimulus intensities during TFT minimizes the stress influences produced by restraint on the animal's response rendering the test more sensitive to the pharmacological action of analgesic drugs. PMID- 1421529 TI - Cell-growth quantitation methods for the evaluation of antiestrogens in human breast cancer cells in culture. AB - The antiproliferative activity of the antiestrogen, tamoxifen, on the growth of MCF-7 human breast cancer cells was evaluated using the hemocytometric trypan blue exclusion method, [3H]-thymidine incorporation, and a total protein determination. Tamoxifen was evaluated over a concentration range from 10(-9) to 10(-6) M. The hemocytometric trypan blue exclusion method and [3H]-thymidine incorporation were sensitive enough to demonstrate the inhibitory influence of tamoxifen on the proliferation of MCF-7 cells at a concentration as low as 10(-9) M. A very good correlation of these two methods was observed in the submicromolar concentration range of tamoxifen. The total protein determination method was only sensitive enough to detect the antiproliferative influence of tamoxifen at concentrations above 10(-6) M. In conclusion, the [3H]-thymidine incorporation method was found to be effective and much less time consuming than the hemocytometric trypan blue exclusion method for evaluating the antiproliferative effects of antiestrogens in cultured MCF-7 cells. However, when evaluating antiestrogens, which are cell-cycle specific, the results of the [3H]-thymidine incorporation method should be interpreted with caution. PMID- 1421530 TI - Quantitative autoradiography of 3H-paroxetine binding sites in rat brain. AB - The use of 3H-paroxetine as a ligand for quantitative autoradiography of serotonin (5-HT) transport sites was optimized, and the distribution of 3H paroxetine binding sites in rat brain was studied. Under the conditions described, 3H-paroxetine binding in forebrain sections was of high affinity and saturable, with a Kd of 0.18 +/- 0.02 nM (mean +/- SEM) and Bmax of 268 +/- 12 fmol/mg of protein (n = 3). Nonspecific binding was 10.7% +/- 1.0 of the total binding (n = 8). The distribution of 3H-paroxetine binding sites closely matched the regional distribution of 5-HT nerve terminals and cell bodies. The highest concentrations of 3H-paroxetine binding sites were found in the dorsal raphe nucleus (563 +/- 55 fmol/mg tissue, n = 4), and high densities of binding were also found in the locus coeruleus, medial forebrain bundle, substantia nigra, several limbic structures (amygdala, hippocampus, hypothalamus, olfactory tubercle, septum, and thalamus), and components of the visual relay system (superior colliculus and the lateral geniculate body). Although lesioning of 5-HT neurons with p-chloroamphetamine (PCA) drastically eliminated 3H-paroxetine binding in most regions of the rat brain, significant binding remained in the raphe nuclei and medial forebrain bundle suggesting that 3H-paroxetine binding in these regions was to presynaptic sites on cell bodies or axons relatively resistant to PCA. PMID- 1421531 TI - Three-dimensional electrocardiography in the rat. AB - Three-dimensional electrocardiography with computerized analysis provides a means to rapidly collect and quantitatively analyze electrocardiographic data from rats. Electrical activity at each point in time can be expressed quantitatively as a vector with magnitude and direction. Rats are fitted with plate and needle electrodes in three mutually perpendicular axes: X (right to left), Y (rostral to caudal), and Z (ventral to dorsal). Electrocardiographic signals are recorded on paper and also collected at 1000/sec using an IBM-compatible computer equipped with a fast A/D convertor. Signals are analyzed using an interactive program written in Turbo PASCAL which transforms data into an array consisting of vector magnitude and direction at each time point. The data are further used to produce both a tabular report and graphic output. This method retains simplicity while extending the accuracy of electrocardiographic (ECG) measurement. It literally adds another dimension of information to the three-lead ECG most commonly measured in rats. PMID- 1421532 TI - Venous thrombosis produced in the vena cava of rabbits by vascular damage and stasis. AB - The main objective of these experiments was to develop and characterize a new experimental model of venous thrombosis, and determine whether a combination of vascular wall damage (crushing with hemostat clamps) and prolonged stasis produced more reproducible clots than prolonged stasis per se. Rabbits were laparotomized, and a segment of the vena cava was dissected free and looped with two silk ligatures, 2.5 cm apart. The proximal tie was ligated 5 min after release of the clamps; the distal tie applied shortly thereafter, trapping a volume of blood in the isolated segment. At 2 hr after ligation, the isolated venous sac was excised and examined for the presence of a clot. Large, well formed clots, which could be readily transferred and weighed, were invariably observed in the "clamp" and "no clamp" groups, the latter being a sham control. Mean clot weights did not differ in the two groups (23.1 +/- 1.6 versus 30.8 +/- 5.4 mg dry weight, clamped versus no clamp, respectively, p greater than 0.05). However, the precision of the method was improved significantly (p less than 0.005) by clamping as determined by homogeneity of variance testing. Time-course studies showed that a considerable lag period (about 60 min) preceded development of a detectable clot, and that the thrombus evolved rapidly during the interval of 60-90 min postligation. The location of the small clots at 60 min in clamped segments, as well as the failure of prolonged (120 min) stasis without caval isolation to cause substantial thrombi, strongly suggests that clot formation attributed to "stasis per se" is in fact due to focal vascular lesions created at the tie-down points. The present study is also the first report of blockade of localized venous thrombosis by recombinant tissue factor pathway inhibitor (rTFPI). When given as an i.v. bolus 20 min prior to ligation, rTFPI at 400 and 800 micrograms/kg completely blocked formation of the thrombus or greatly reduced its size in five of the six animals tested. PMID- 1421533 TI - A computerized method for measurement and analysis of blood pressure in small animals. AB - A method is described for computerized measurement of blood pressure (BP) in small animals. As described, the system measures BP in up to four experimental animals at one time by sequential sampling but can be expanded to take data from up to 10. It requires an Apple II computer, and is run from a Grass pen-recording system. Pulse rate and systolic and diastolic BP are measured, and these variables are used to calculate mean arterial pressure (MAP) and the time integral of MAP minute by minute. The data are displayed in real time and stored hourly on floppy disc for further analysis. PMID- 1421534 TI - Gastric mucosal damage due to aspirin and copper aspirinate assessed by gastric mucosal potential difference changes. AB - When the gastric mucosa is damaged by antiinflammatory agents, such as aspirin, gastric mucosal potential difference (GPD) decreases and may or may not return to predamage values after the agent is removed. The magnitude and time course of the gastric potential difference changes have been suggested as a measure of mucosal damage. Male Sprague-Dawley rats were fasted, anesthetized, and surgically prepared for measurement of GPD by placement of electrodes in the gastric lumen and spleen. Test mixtures of aspirin, copper aspirinate, copper sulfate, or mixtures of aspirin and copper sulfate were administered by gavage, and subsequent changes in GPD were recorded. The area between the extrapolated control (baseline) GPD and the damage GPD was determined. The product of this area and the maximum change in GPD, the Reizindex (RI), was calculated. Values for all copper (II)-containing systems, including those with no aspirin, were significantly greater than aspirin alone. It was concluded that factors other than mucosal damage may contribute to a reduction in GPD and, therefore, an increase in Reizindex. PMID- 1421535 TI - Consensus on laparoscopic surgery. PMID- 1421536 TI - Laparoscopic hernioplasty update. AB - The Toy-Smoot laparoscopic hernioplasty has been performed on 75 patients with a total of 83 hernioplasties over the past 20 months. Sixty-nine patients were male and six were female. The age range was 20 to 75 years with an average age of 51.5 years. Twelve of the patients had bilateral hernias repaired: 55 direct hernias, 16 indirect hernias, and 5 pantaloon hernias. Eleven of the repairs were for recurrent hernias. The procedure was performed under general anesthesia. The abdomen was insufflated with carbon dioxide, establishing the pneumoperitoneum. Three 11 mm trocars were inserted, the first via the umbilicus, into which the 0 degrees endoscope was inserted. Two additional trocars were inserted at the level of the umbilicus at the anterior axillary lines. The hernia sacs were left in situ. The medial umbilical ligament was dissected medially, so as to identify directly the pubic tubercle and the Cooper's ligament. An expanded PTFE soft tissue patch, 1 mm thick and 7.5 x 10 cm in size, was attached to the Nanticoke Endo-patch spreader and introduced via the contralateral trocar and positioned over the hernia defect. The Endopath EMS stapler was then used to secure the PTFE patch over the hernia defect. This required secure anatomical fixation to the transversalis fascia anteriorly and laterally, the pubic tubercle, and the posterior rectus sheath, medially, Cooper's ligament, posteromedially, and the endoabdominal fascia, posterolaterally. There were a total of seven different complications, one major, which was a bladder injury that required an open repair of the bladder and then an open, conventional hernioplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421537 TI - A novel endoscopic transgastric fundoplication procedure for gastroesophageal reflux: an initial animal evaluation. AB - Complications of gastroesophageal reflux are common in adults and children. A variety of surgical procedures have been successfully used to treat this condition. All current techniques require open surgery and are associated with significant morbidity and mortality, particularly in the high risk, neurologically damaged child. The authors have developed a novel method of creating a gastric fundoplication using an endoscopic transgastric approach in pigs. The procedure involves the creation of an esophageal intussusception into the stomach under direct vision with an endoscope. The gastric fundus is then plicated around the esophagus using a custom stapling device. The transgastric approach allows creation of a fundoplication, is easily performed, is potentially effective at preventing gastroesophageal reflux, and has the obvious advantages of minimally invasive surgery over open techniques of fundoplication. PMID- 1421538 TI - Why catheterize the bladder for laparoscopic cholecystectomy? AB - Bladder catheterization is widely employed for laparoscopic cholecystectomy. Fifty consecutive laparoscopic cholecystectomies were performed without bladder catheterization. Patients were asked to void shortly before induction of anesthesia to ensure that the bladder was empty. Postoperative bladder catheterization for urinary retention was required in 3 of the 50 patients. Routine bladder catheterization for laparoscopic cholecystectomy is unnecessary, and its elimination will reduce costs, urethral trauma, and nosocomial urinary tract infections. PMID- 1421539 TI - Extraperitoneal endoscopic pelvic lymph node dissection vs. laparoscopic lymph node dissection in the staging of prostatic and bladder carcinoma. AB - Eighteen patients undergoing laparoscopic pelvic lymphadenectomy were compared with eighteen patients undergoing lymph node dissection performed via a totally extraperitoneal approach called extraperitoneal endoscopic pelvic lymph node dissection. Operative time, nodal yield, and hospital stays were essentially the same in both groups. However, the laparoscopic approach had a greater incidence of morbidity, leading the authors to adopt a totally extra-peritoneal endoscopic approach to pelvic lymph node dissection. Advantages of using an extraperitoneal approach are presented. PMID- 1421540 TI - Three-dimensional transrectal ultrasound: preliminary patient evaluation. AB - Transrectal ultrasound is uniquely useful in diagnosing and localizing the extent of lower colon and rectal disease. This paper reports the preliminary evaluation of three-dimensional intraluminal ultrasound imaging of normal and diseased rectal segments. The three-dimensional reconstructions were produced using a computerized PC based image analysis system which aligns ultrasound images to produce the three-dimensional images. A unique perspective for displaying both normal and pathologic anatomy is achieved using this new technology and the method has promising diagnostic and therapeutic potentials. PMID- 1421541 TI - Hernioscopy: laparoscopy via an inguinal hernia sac. AB - The use of laparoscopy in general surgery has expanded to aid in the diagnosis of various intraabdominal conditions. A new application of the laparoscope is described to explore the abdominal cavity for potential gangrenous bowel after reduction of an incarcerated inguinal hernia. Hernioscopy allows for a good view of the entire abdomen including inspection of the colon for serosal changes of carcinoma. Exploration via this technique is accomplished without additional skin incisions or fascial disruptions and with no increased morbidity, when performed during the inguinal herniorrhaphy. PMID- 1421542 TI - Aortic laceration: a rare complication of laparoscopy. AB - Aortic laceration during laparoscopic procedures is a rare but well-known complication with a high mortality rate. Thus far, few cases which were recognized and treated successfully have been reported in the literature; the exact incidence is not known. Such a complication occurred after an elective laparoscopic sterilization in a 35-year-old woman. The situation was recognized early and successfully treated. The common complications of laparoscopy are usually of a minor nature but a few are life threatening. This case illustrates the need for emphasis on the prevention of complications and the appropriate course of action in the event of their occurrence. PMID- 1421543 TI - Laparoscopy in the diagnosis and treatment of acute small bowel obstruction. AB - The surgical correction of acute small bowel obstruction is conventionally performed through a vertical laparotomy incision. The increasing use of the laparoscope for elective general surgery has led to an increase in its use for the diagnosis and treatment of acute abdominal conditions. The authors report five cases of acute small bowel obstruction treated with the aid of the laparoscope. All five patients were able to leave the hospital in the early postoperative period and remain symptom free. Laparoscopy is a useful technique in the management of selected cases of small bowel obstruction. PMID- 1421544 TI - Laparoscopic cholangiography: a new method and device. AB - Laparoscopic cholangiography is invaluable in the detection of bile duct stones, visualization of ductal anomalies and discovery and prevention of iatrogenic injuries to the bile ducts. The use of this procedure is, however, limited by the technical difficulties of cystic duct cannulation. A method of laparoscopic cholangiography that avoids cystic duct cannulation is described. It consists of a Kumar I Cholangiography Clamp that is applied across the gallbladder just above the Hartmann's pouch and divides the gallbladder into a medial and lateral compartment. A Kumar Cholangio Catheter is then introduced through the side channel of the clamp, puncturing the medial compartment (i.e. the Hartmann's pouch) with a short #22 gauge needle for aspiration, followed by dye injection. Cholangiography was obtained with remarkable ease in 49 of the first 50 cases (98%) without complication. PMID- 1421545 TI - Percutaneous endoscopic implantation of Automatic Implantable Cardioverter/Defibrillator (AICD): an animal study of a new nonthoracotomy technique. AB - The Automatic Implantable Cardioverter/Defibrillator (AICD) prevents death due to malignant ventricular arrhythmias but requires thoracotomy for the implantation of the preferred two-patch lead system. The purpose of this study was to develop and test a new percutaneous endoscopic method of the AICD lead implantation without the need for open chest surgery. A high resolution video endoscopy system and currently available endoscopic instrumentation were used to develop pleural pericardial dissection technique in 7 pigs and to endoscopically implant custom made AICD patches in 20 pigs. An examining 10 mm rigid endoscope inserted in the 6th intercostal space in the anterior axillary line provided direct visual control for endoscopic dissection of the parietal pleura from the pericardium, delivery, and implantation of the AICD patches. This was successfully carried out through two trocars (10 and 11 mm) inserted into the pleural-pericardial space via the subxyphoid approach in 18 of 20 pigs. Effective patch positioning was confirmed by attaining a defibrillation threshold of 20J or less in 13 pigs. Of those, three required lead polarity reversal, and three others required lead repositioning to lower defibrillation thresholds to 20J or less. In three pigs, defibrillation thresholds of 30J or higher were required. Defibrillation was unsuccessful in two pigs due to patch malfunction. The authors conclude that percutaneous endoscopy is a feasible method of AICD lead implantation. PMID- 1421546 TI - Laparoscopic pericardial window. AB - The patient with a malignant pericardial effusion can be extremely difficult to treat and provide optimal palliation. The performance of transabdominal laparoscopic pericardial window may prove to be a significant advance in the management of these individuals. No previously reported description of this procedure has been found in the world literature as far back as 1966. A presentation of the case, description of the surgical procedure, and discussion of the therapeutic implications are provided. PMID- 1421547 TI - The need for improving laparoscopic suturing and knot-tying. PMID- 1421548 TI - A technique for extracorporeal suturing. AB - Advances in laparoscopic surgical procedures will be facilitated by the ability to perform suturing efficiently and effectively. A simple technique of extracorporeal suturing is described, which permits rapid and reliable knot placement for a wide variety of laparoscopic procedures. PMID- 1421549 TI - A technique of laparoscopic knot tying. PMID- 1421550 TI - Ultrastructural histopathology of human olfactory dysfunction. AB - This paper presents electron-microscopic observations on biopsies of the olfactory mucosae of several classes of patients with smell disorders: 1) patients with loss of smell function following head injury (post-traumatic anosmics or hyposmics); 2) patients with loss of smell function following severe head colds and/or sinus infections (post-viral olfactory dysfunction, or PVOD); and 3) patients that have lacked smell function since birth (congenital anosmics). Of these, the traumatic anosmics' olfactory epithelia were quite disorganized; the orderly arrangement of supporting cells, ciliated olfactory receptor neurons, microvillar cells, and basal cells was disrupted. Although many somata of ciliated olfactory receptors were present, few of their dendrites reached the epithelial surface. The few olfactory vesicles present usually lacked olfactory cilia. The post-viral anosmics, too, had a greatly reduced number of intact ciliated olfactory receptor neurons, and most of those present were aciliate. The post-viral hyposmics had a larger population of intact, ciliated olfactory receptor cells. In the seven cases of congenital anosmia studied, no biopsies of olfactory epithelium were obtained, indicating the olfactory epithelium is either absent--or greatly reduced in area--in these individuals. PMID- 1421551 TI - Fine structural aspects of secretion and extrinsic innervation in the olfactory mucosa. AB - The mucus at the surface of the olfactory mucosa constitutes the milieu in which perireceptor events associated with olfactory transduction occur. In this review, the ultrastructure of olfactory mucus and of the secretory cells that synthesize and secrete olfactory mucus in the vertebrate olfactory mucosa is described. Bowman's glands are present in the olfactory mucosa of all vertebrates except fish. They consist of acini, which may contain mucous or serous cells or both, and ducts that traverse the olfactory epithelium to deliver secretions to the epithelial surface. Sustentacular cells are present in the olfactory epithelium of all vertebrates. In fish, amphibia, reptiles, and birds, they are secretory; in mammals, they generally are considered to be "non-secretory," although they may participate in the regulation of the mucous composition through micropinocytotic secretion and uptake. Goblet cells occur in the olfactory epithelium of fish and secrete a mucous product. Secretion from Bowman's glands and vasomotor activity in the olfactory mucosa are regulated by neural elements extrinsic to the primary olfactory neurons. Nerve fibers described in early anatomical studies and characterized by immunohistochemical studies contain a variety of neuroactive peptides and have several targets within the olfactory mucosa. Ultrastructural studies of nerve terminals in the olfactory mucosa have demonstrated the presence of adrenergic, cholinergic and peptidergic input to glands, blood vessels, and melanocytes in the lamina propria and of peptidergic terminals in the olfactory epithelium. The neural origins of the extrinsic nerve fibers and terminals are the trigeminal, terminal, and autonomic systems. PMID- 1421552 TI - Endocytic pathways in the olfactory and vomeronasal epithelia of the mouse: ultrastructure and uptake of tracers. AB - Mammalian olfactory neurons possess a well-developed system of endocytic vesicles, endosomes, and lysosomes in their dendrites and perikarya. Vomeronasal neurons are similar and also contain much perikaryal agranular endoplasmic reticulum (AER). Olfactory supporting cells contain endocytic vesicles and endosomes associated closely with abundant fenestrated AER, and vesicles and numerous large dense vacuoles are present basally. Vomeronasal supporting cells have little AER, and few dense vacuoles occur in their bases. In olfactory neurons, ultrastructural tracers (0.08% horseradish peroxidase, thorium dioxide, ferritin) are endocytosed by olfactory receptor endings and transported to the cell body, where their movement is halted in lysosomes. Higher concentrations (1%) of horseradish peroxidase penetrate olfactory receptor plasma membranes and intercellular junctions. In olfactory supporting cells, endocytosed tracers pass through endosomes to accumulate in dense basal vacuoles. These observations indicate that olfactory sensory membranes are rapidly cycled and that endocytosed materials are trapped within the epithelium. It is proposed that in the olfactory epithelium, endocytosis presents redundant odorants to the enzymes of the supporting cell AER to prevent their accumulation, whereas in the vomeronasal epithelium the receptor cells carry out this activity. PMID- 1421553 TI - Ultrastructural studies of microtubules and microtubule organizing centers of the vertebrate olfactory neuron. AB - The olfactory neuron is specialized along its length into highly determined morphological regions. These regions include the dendritic cilia, dendritic vesicle, dendritic shaft proper, perikaryon, axon, zone of transition where the axon widens as it approaches its termination, and the axon terminal. Except for the zone of transition and the terminal, characteristic populations of microtubules occur in these compartments. In the olfactory vesicle, three discrete microtubule organizing centers (MTOCs) nucleate microtubules: the basal body, the lateral foot associated with the body, and dense masses of nearby material. Little is known about MTOCs elsewhere in the neuron, although the polarity of the axonal microtubules indicate that they originate at or near the perikaryon. An attempt is made to summarize what is known of the origin, structure, distribution, and function of microtubules in vertebrate olfactory neurons, which are useful model systems in which to study microtubules. Information about olfactory neuron microtubules may be applicable to neurons in general (e.g., the discovery that axons contain microtubules of uniform polarity was first made in the olfactory neuron) or to microtubules in other eukaryotic cells. PMID- 1421554 TI - Growth of olfactory epithelial tissue in vitro: lectin staining of axons. AB - In vitro methods have been used to study several aspects of development of olfactory epithelium. In this paper, the value of growing olfactory tissue in explant cultures is reviewed and some experiments are reported on the identification of lectin receptors on olfactory axons by the use of lectin-gold complexes. Both concanavalin A-gold (con A-gold) and wheat germ agglutinin-gold consistently decorated olfactory axons in explant cultures. Con A-gold also bound to the tips of growth cone filopodia, suggesting the glycoconjugate molecules containing alpha-methyl-pyranoside are important in adherence of growth cones to their substrate. The wide range in density of lectin-gold particles suggested that axons, and the sensory cells from which they arise, are not a uniform population, i.e., they have different molecular fingerprints. This was supported by the observation that soybean agglutinin-gold stained some axons very well, but others remained unstained. Peanut agglutinin did not bind to any axons. PMID- 1421555 TI - Lectins bind differentially to cilia and microvilli of major and minor cell populations in olfactory and nasal respiratory epithelia. AB - Binding of colloidal gold-conjugated lectins was studied in cilia and microvilli of rat olfactory and respiratory epithelia. This was done in sections of rapidly frozen, freeze-substituted specimens embedded in Lowicryl K11M or, for wheat germ agglutinin (WGA) alone, in deep-etched replicas. Olfactory dendritic endings and cilia labeled with WGA and faintly with soybean agglutinin (SBA); olfactory supporting cell microvilli bound only Dolichos biflorus agglutinin (DBA). Microvilli of an infrequent cell bound peanut agglutinin (PNA), SBA, and WGA. These microvilli labeled more strongly with the last two lectins than the olfactory cilia. Respiratory cilia bound WGA and, somewhat more weakly, PNA; microvilli of ciliated respiratory cells bound all four lectins. Visualization of specific labeling improved after preincubation of sections with neuraminidase, except for DBA where lectin binding was abolished. PNA labeling was seen only after neuraminidase preincubation. The densities of membrane surface particles that labeled with WGA corresponded with those of fracture plane particles in a quantitative freeze-fracture, deep-etch analysis. Therefore, a considerable fraction of the WGA-bound particles could reflect transmembrane proteins in olfactory dendritic endings and cilia and in respiratory cilia. The possible nature of these particles is discussed. PMID- 1421556 TI - Depo provera treatment for sex offending behavior: an evaluation of outcome. AB - Forty men, ages 16 to 78 years, with sex-offending behavior, were treated with combined medroxyprogesterone acetate (MPA), group therapy, and individual psychotherapy. Twenty-three are pedophiles; seven, rapists; and 10, exhibitionists. Five had sex-offending behavior that began after head trauma. The duration of MPA therapy, usual intramuscular dose 400 mg/wk, ranged from six months to 12 years, usually more than two years. These men were compared with a control group of 21 men who refused MPA therapy. They had similar types of sex offending behavior and were treated with psychotherapy alone with follow-up for a period that ranged from two to 12 years. MPA-related side effects included excessive weight gain, malaise, migraine headaches, severe leg cramps, elevation of blood pressure, gastrointestinal complaints, gallbladder stones, and diabetes mellitus. Of the 40 individuals who took MPA, 10 are still on therapy. Eighteen percent reoffended while receiving MPA therapy; 35 percent reoffended after stopping MPA. In contrast, 58 percent of the control patients, who refused and never received MPA, reoffended. Patients defined as regressed were much more likely to reoffend off therapy than the patients defined as fixated. Other risk factors for reoffense include elevated baseline testosterone, previous head injury, never forming a marriage relationship, and alcohol and drug abuse. In spite of significant medical side effects, maintenance MPA offers benefit for the compulsive sex offender by reducing the reoffense rate. PMID- 1421557 TI - Incompetence, treatment refusal, and hospitalization. AB - Psychiatrists have proposed broadened commitment statues based on need for care and treatment, and under which judges have no role in deciding cases of treatment refusal. The mental health bar has consistently opposed these proposals on constitutional and common law grounds. The authors propose new commitment criteria based on incompetency to decide about hospitalization, and inability to live safely in freedom. The proposed standards would meet the Constitutional requirements, and would permit hospitalization and/or treatment for many persons who are in need but who now go without. The authors recognize that new commitment law without adequate clinical resources will not greatly improve patient care. PMID- 1421558 TI - Treatment boundary violations: clinical, ethical, and legal considerations. AB - The observance of treatment boundaries maintains the integrity of the therapist patient relationship. It is the therapist's professional duty to establish appropriate treatment boundaries. Basic boundary guidelines are reviewed. The principles underlying these boundary guidelines are explored. A clinical vignette describing the sexual exploitation of a patient by her therapist dramatically illustrates progressive boundary violations. Boundary violations involving money are particularly common. Double agent roles also are likely to lead to the establishment of dissonant treatment boundaries with patients. The clinical, ethical, and legal issues surrounding the maintenance of treatment boundaries are discussed. PMID- 1421559 TI - Approaches to forensic assessment of false claims of sexual misconduct by therapists. AB - The author offers systematic approaches to evaluation of claims of therapist patient sexual misconduct, together with their rationales. False accusations should be considered in all such cases in order to maintain the balanced forensic perspective and to probe for malingering, as in all evaluations. Practical techniques are offered and the underlying reasoning described. PMID- 1421560 TI - The impact of clozapine on 25 forensic patients. PMID- 1421561 TI - Collision between law and ethics: consent for treatment with adolescents. AB - The dilemmas between legal obligations and ethical responsibilities can often create problems in clinical work. The treatment of minors, and particularly adolescents, can present special issues to the clinician that are becoming increasingly frequent and difficult. The issue of informed consent for treatment of adolescents raises serious questions for the clinical practitioner who is faced with both legal and ethical dilemmas in making decisions about treatment. There are an increasing number of cases where adolescents may seek treatment yet are in circumstances that preclude parental consent. This paper uses case material to illustrate some of the legal, ethical, and treatment considerations in the situation of adolescent treatment where parental consent is problematic. PMID- 1421562 TI - The occupational hazards of jury duty. AB - Jurors on criminal trials carry a considerable burden of responsibility. They determine the defendant's fate. Additionally, during trials they can be exposed to stressful, frightening, and sordid aspects of life. The stressfulness varies depending upon the nature of the trial, its length, the nature of the testimony and evidence, the jurors' interpersonal relationships, the difficulty establishing guilt or innocence, the public's attitude, etc. These experiences can create psychological and/or physical discomfort that can be transient and mildly or moderately intense, or more serious and constitute illness. The authors have studied juries of four criminal trials--two murder cases, one child abuse case, and one obscenity case. Forty jurors were interviewed. Twenty-seven had one or more discomforting physical and/or physiological symptoms. These involved gastrointestinal distress (10 jurors); generalized nervousness (4 jurors); heart palpitation (6 jurors); headaches (4 jurors); sexual inhibitions (4 jurors); depression (4 jurors); anorexia (4 jurors); faintness (2 jurors); and numbness, lump in throat, chest pain, hives, and flu (1 juror each). Seven of the jurors became clearly ill. Illnesses included: peptic ulcer reactivation and hives, phobic reaction, anxiety state and increased alcohol use, hypertensive episode and visual scotomata, sexual inhibition, chills, fever, and depression, and post traumatic stress disorder. PMID- 1421563 TI - The Tarasoff raid: a new extension of the duty to protect. AB - The authors discuss the general outlines of the Tarasoff duty of psychotherapists to protect potential victims of their violent patients. They describe the flexible range of clinical responses that therapists have utilized, as well as their professional concerns about preserving patient confidentiality (or at least strictly circumscribing the scope of disclosure when confidentiality must be breached). A recent case is reported that illustrates a striking new extension of Tarasoff, involving a police search and seizure of a psychotherapist's confidential treatment records and tapes, in response to a third-party complaint that the records contained evidence of his patients' violent acts and propensities. The implications of this case are that the therapist's discretion in the assessment of his duty to protect, the selection of a proper course of action, and the implementation of specific responses may be taken out of his hands, for all intents and purposes, and expropriated by law and order officials. Moreover, regardless of whatever clinical approach he adopts and whether or not he issues a warning, his attempts to preserve patient confidentiality are bound to prove unsuccessful in any future legal proceedings. Patient communications are likely to lose their confidential status on the grounds that they caused or triggered the Tarasoff warning (or that they should have triggered it). If the patient directed serious threats against the therapist himself, the court may find that, as a consequence, a "genuine therapeutic relationship" ceased to exist and thereafter all patient disclosures were no longer confidential on that basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421564 TI - Peer review of psychiatric expert testimony. American Psychiatric Association's Council on Psychiatry and Law. PMID- 1421566 TI - Endoplasmic reticulum: a dynamic patchwork of specialized subregions. PMID- 1421567 TI - Activation of a muscle-specific actin gene promoter in serum-stimulated fibroblasts. AB - Treatment of AKR-2B mouse fibroblasts with serum growth factors or inhibitors of protein synthesis, such as cycloheximide, results in a stimulation of cytoskeletal beta-actin transcription but has no effect on transcription of muscle-specific isotypes, such as the vascular smooth muscle (VSM) alpha-actin gene. Deletion mapping and site-specific mutagenesis studies demonstrated that a single "CArG" element of the general form CC(A/T)6GG was necessary and possibly sufficient to impart serum and cycloheximide-inducibility to the beta-actin promoter. Although the VSM alpha-actin promoter exhibits at least three similar sequence elements, it remained refractory to serum and cycloheximide induction. However, deletion of a 33 base pair sequence between -191 and -224 relative to the transcription start site resulted in the transcriptional activation of this muscle-specific promoter in rapidly growing or serum-stimulated fibroblasts. Although the activity of this truncated promoter was potentiated by cycloheximide in a manner indistinguishable from that of the beta-actin promoter, this was dependent on a more complex array of interacting elements. These included at least one CArG box and a putative upstream activating element closely associated with the -191 to -224 inhibitory sequences. These results demonstrate that the expression of a muscle-specific actin gene in fibroblasts is suppressed by a cis acting negative control element and that in the absence of this element, the promoter is responsive to growth factor-induced signal transduction pathways. PMID- 1421568 TI - Ability of adenovirus 5 E1A proteins to suppress differentiation of BC3H1 myoblasts correlates with their binding to a 300 kDa cellular protein. AB - We have used deletion mutants to define the regions in Ad5 E1A proteins necessary to suppress differentiation of mouse BC3H1 myoblasts. We examined the differentiation of cells infected at a low multiplicity with viruses containing the E1A deletions and constructed so as to produce only the smaller of the two major E1A proteins. Only four of the mutant viruses containing deletions within the N-terminal 69 residues failed to suppress differentiation as judged by changes in morphology and in levels of muscle-specific alpha-actin mRNA and creatine kinase activity. The results were confirmed by analyses of lines of cells stably transfected with representative E1A mutants. The mouse cellular proteins to which mutant E1A proteins bound were identified by immunoprecipitating E1A proteins specifically from infected BC3H1 cells and by analyzing the precipitates on denaturing gels. Bands of proteins of 300, 130, 107, 105 (the retinoblastoma product), and 60 kDa (cyclin A) were distinguished. Failure to suppress differentiation correlated with loss of binding to the 300 kDa protein but not to any of the others. The regions of E1A defined in this way have been shown to be required for several other activities, including enhancer repression and transformation. One function of the 300-kDa protein appears to be to facilitate the action of transcriptional enhancers of differentiation-specific genes. PMID- 1421565 TI - The extracellular regulation of growth factor action. PMID- 1421569 TI - Inhibition of c-Jun DNA binding by mitogen-activated protein kinase. AB - Here we demonstrate that partially purified Xenopus p42 mitogen-activated protein (MAP) kinase phosphorylates bacterially expressed human c-Jun at a single site, serine 243. Several lines of evidence argue that this phosphorylation is due to p42 MAP kinase itself rather than some contaminating species. Phosphorylation of serine 243 markedly decreases the binding of c-Jun to oligonucleotides containing the 12-O-tetradecanoylphorbol-13-acetate response element. These findings suggest that MAP kinase may play a role in the down-regulation of c-Jun or in the cycle of transcriptional initiation and elongation. PMID- 1421570 TI - Induction of NF-kappa B-like activity by platelet-derived growth factor in mouse fibroblasts. AB - Nuclear factor kappa B (NF-kappa B) modulates the expression of numerous genes via interaction with a specific DNA sequence termed the kappa B site. Its activity is modulated by a cytosolic inhibitor protein termed I kappa B, and its activation occurs in response to a variety of agents in a variety of cell types, most notably B and T lymphocytes. Data presented here show that an activity (designated complex I) that binds specifically to the kappa B site is induced in density-arrested Balb/c-3T3 mouse fibroblasts by platelet-derived growth factor (PDGF), a potent mitogen for these cells. Increased levels of complex I, as evaluated by electrophoretic mobility shift assays of nuclear extracts, were observed in cells treated for 1-4 h (but not 15 min) with the BB isoform of PDGF. 12-O-tetradecanoylphorbol 13-acetate (TPA) and the AA isoform of PDGF also stimulated this response and both isoforms, but not TPA, were effective in cells depleted of protein kinase C. Complex I most likely is authentic NF-kappa B, a p50-p65 heterodimer, or a closely related factor because it exhibited properties characteristic of those previously described for NF-kappa B including inducibility by deoxycholate and cycloheximide and sensitivity to I kappa B. A second kappa B binding activity (complex II), which apparently contained p50 homodimers, displayed limited induction by PDGF, whereas a third complex (complex III) migrated faster than but behaved similarly to complex I. These studies suggest that NF-kappa B or an NF-kappa B-like factor may participate in the expression of PDGF-inducible genes. PMID- 1421571 TI - Modulation of the dynamic instability of tubulin assembly by the microtubule associated protein tau. AB - Microtubule-associated proteins (MAP), such as tau, modulate the extent and rate of microtubule assembly and play an essential role in morphogenetic processes, such as axonal growth. We have examined the mechanism by which tau affects microtubule polymerization by examining the kinetics of microtubule assembly and disassembly through direct observation of microtubules using dark-field microscopy. Tau increases the rate of polymerization, decreases the rate of transit into the shrinking phase (catastrophe), and inhibits the rate of depolymerization. Tau strongly suppresses the catastrophe rate, and its ability to do so is independent of its ability to increase the elongation rate. Thus, tau generates a partially stable but still dynamic state in microtubules. This state is perturbed by phosphorylation by MAP2 kinase, which affects all three activities by lowering the affinity of tau for the microtubule lattice. PMID- 1421572 TI - Role of GTP hydrolysis in microtubule dynamics: information from a slowly hydrolyzable analogue, GMPCPP. AB - The role of GTP hydrolysis in microtubule dynamics has been reinvestigated using an analogue of GTP, guanylyl-(alpha, beta)-methylene-diphosphonate (GMPCPP). This analogue binds to the tubulin exchangeable nucleotide binding site (E-site) with an affinity four to eightfold lower than GTP and promotes the polymerization of normal microtubules. The polymerization rate of microtubules with GMPCPP-tubulin is very similar to that of GTP-tubulin. However, in contrast to microtubules polymerized with GTP, GMPCPP-microtubules do not depolymerize rapidly after isothermal dilution. The depolymerization rate of GMPCPP-microtubules is 0.1 s-1 compared with 500 s-1 for GDP-microtubules. GMPCPP also completely suppresses dynamic instability. Contrary to previous work, we find that the beta--gamma bond of GMPCPP is hydrolyzed extremely slowly after incorporation into the microtubule lattice, with a rate constant of 4 x 10(-7) s-1. Because GMPCPP hydrolysis is negligible over the course of a polymerization experiment, it can be used to test the role of hydrolysis in microtubule dynamics. Our results provide strong new evidence for the idea that GTP hydrolysis by tubulin is not required for normal polymerization but is essential for depolymerization and thus for dynamic instability. Because GMPCPP strongly promotes spontaneous nucleation of microtubules, we propose that GTP hydrolysis by tubulin also plays the important biological role of inhibiting spontaneous microtubule nucleation. PMID- 1421573 TI - Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces. AB - Osteopontin, a glycoprotein with a glycine-arginine-glycine-aspartate-serine (GRGDS) cell-binding domain, has been described in bone and is also known to be expressed in other organs, particularly kidney. The goal of the present work was to define the distribution of osteopontin synthesis and deposition in a wide variety of normal adult human tissues using a multifaceted approach that included immunohistochemistry, in situ hybridization, and Northern analysis. Immunohistochemical studies have revealed the unexpected finding that osteopontin is deposited as a prominent layer at the luminal surfaces of specific populations of epithelial cells of the gastrointestinal tract, gall bladder, pancreas, urinary and reproductive tracts, lung, breast, salivary glands, and sweat glands. Northern analyses identified gallbladder as a major site of osteopontin gene transcription comparable in magnitude with that of kidney, and immunoblotting identified osteopontin in bile. In situ hybridization localized osteopontin gene transcripts predominantly to the epithelium of a variety of organs as well as to ganglion cells of bowel wall. Osteopontin of epithelial cell origin, like bone derived osteopontin, promoted GRGDS-dependent cell spreading in attachment assays. We postulate that osteopontin secreted by epithelium binds integrins on luminal surfaces. Collectively, these findings suggest an important role for osteopontin on many luminal epithelial surfaces communicating with the external environment. PMID- 1421574 TI - Interaction of dynamin with microtubules: its structure and GTPase activity investigated by using highly purified dynamin. AB - We purified a large amount of dynamin with high enzymatical activity from rat brain tissue by a new procedure. Dynamin 0.48 mg was obtained from 20 g of rat brain. The purity of dynamin was almost 98%. Dynamin plays a role of GTPase rather than ATPase. In the absence of microtubules, Michaelis constant (Km) and maximum velocity (Vmax) for dynamin GTPase were 370 microM and 0.25 min-1, respectively, and in their presence, both were significantly accelerated up to 25 microM and 5.5 min-1. On the other hand, the ATPase activity was very low in the absence of microtubules, and even in their presence, Km and Vmax for dynamin ATPase were 0.2 mM and 0.91 min-1. Despite slow GTPase turnover rate in the absence of microtubules, binding of GTP and its nonhydrolizing analogues was very fast, indicating that GTP binding step is not rate limiting. Dynamin did not cause a one-directional consistent microtubule sliding movement just like kinesin or dynein in the presence of 2 mM ATP or 2 mM GTP. We observed the molecular structure of dynamin with low-angle rotary shadowing technique and revealed that the dynamin molecule is globular in shape. Gel filtration assay revealed that these globules were the oligomers of 100-kDa dynamin polypeptide. Dynamin bound to microtubules with a 1:1 approximately 1.2 molar ratio in the absence of GTP. Quick-freeze deep-etch electron microscopy of the dynamin-microtubule complex showed that dynamin decorates the surface of microtubules helically, like a screw bolt, very orderly and tightly with 11.4 +/- 0.9 (SD)nm period. Contrary to the previous report, microtubules make bundles by the attachment of the dynamin helixes around each adjacent microtubule, and no cross-bridge formation was observed. PMID- 1421575 TI - Specification of sites for polarized growth in Saccharomyces cerevisiae and the influence of external factors on site selection. AB - Many eucaryotic cell types exhibit polarized cell growth and polarized cell division at nonrandom sites. The sites of polarized growth were investigated in G1 arrested haploid Saccharomyces cerevisiae cells. When yeast cells are arrested during G1 either by treatment with alpha-factor or by shifting temperature sensitive cdc28-1 cells to the restrictive temperature, the cells form a projection. Staining with Calcofluor reveals that in both cases the projection usually forms at axial sites (i.e., next to the previous bud scar); these are the same sites where bud formation is expected to occur. These results indicate that sites of polarized growth are specified before the end of G1. Sites of polarized growth can be influenced by external conditions. Cells grown to stationary phase and diluted into fresh medium preferentially select sites for polarized growth opposite the previous bud scar (i.e., distal sites). Incubation of cells in a mating mixture results in projection formation at nonaxial sites: presumably cells form projections toward their mating partner. These observations have important implications in understanding three aspects of cell polarity in yeast: 1) how yeast cell shape is influenced by growth conditions 2) how sites of polarized growth are chosen, and 3) the pathway by which polarity is affected and redirected during the mating process. PMID- 1421576 TI - Myosin II phosphorylation and the dynamics of stress fibers in serum-deprived and stimulated fibroblasts. AB - The actin-based cytomatrix generates stress fibers containing a host of proteins including actin and myosin II and whose dynamics are easily observable in living cells. We developed a dual-radioisotope-based assay of myosin II phosphorylation and applied it to serum-deprived fibroblasts treated with agents that modified the dynamic distribution of stress fibers and/or altered the phosphorylation state of myosin II. Serum-stimulation induced an immediate and sustained increase in the level of myosin II heavy chain (MHC) and 20-kDa light chain (LC20) phosphorylation over the same time course that it caused stress fiber contraction. Cytochalasin D, shown to cause stress fiber fragmentation and contraction, had little effect on myosin II phosphorylation. Okadaic acid, a protein phosphatase inhibitor, induced a delayed but massive cell shortening preceded by a large increase in MHC and LC20 phosphorylation. Staurosporine, a kinase inhibitor known to effect dissolution but not contraction of stress fibers, immediately caused an increase in MHC and LC20 phosphorylation followed within minutes by the dephosphorylation of LC20 to a level below that of untreated cells. We therefore propose that the contractility of the actin-based cytomatrix is regulated by both modulating the activity of molecular motors such as myosin II and by altering the gel structure in such a manner as to either resist or yield to the tension applied by the motors. PMID- 1421578 TI - Biology education is the scientific future. PMID- 1421577 TI - Phosphorylation of p90 and p52 in response to phorbol-esters in Swiss/3T3 cells overexpressing protein kinase C-alpha. AB - Cell lines stably overexpressing protein kinase C (PKC)-alpha were previously described by us. These cell lines were generated by the introduction of the full length cDNA coding for PKC-alpha into Swiss/3T3 cells. Here we show that activation of PKC-alpha by phorbol-esters induced in these cells specific phosphorylation of two cellular proteins p90 and p52. Phosphorylation of p80 (MARCKS protein), previously identified as a substrate for PKC, was also enhanced. Phosphorylated p90 and p52 proteins were associated with particulate membrane-enriched fractions and were extractable with the use of nonionic detergents. Time course analysis of phorbol-ester induced phosphorylation of p90 and p52 revealed maximal stimulation of phosphorylation after 15-30 min. Phosphamino acid analysis showed that phosphorylation of p90 and p52 occurred mainly on serine residues. Phosphorylation of p52 was also on threonine residues. Whereas, phorbol ester activation induced phosphorylation of both p90 and p52, the mitogens platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) enhanced phosphorylation of p90, but not p52. Thus, our studies showed the involvement of PKC-alpha in the regulation of p90 and p52 phosphorylation and provided direct evidence for the role of PKC-alpha in cellular signaling by PDGF and FGF. Moreover, the fact that phosphorylation of p52 was specific to phorbol ester activation may suggest its involvement in tumor promotion. Characterization of p90 and p52 will enable us to reveal the phosphorylation cascade activated downstream to PKC-alpha and to determine their role in mitogenic signaling and tumor promotion. PMID- 1421579 TI - Chromosome loss, hyperrecombination, and cell cycle arrest in a yeast mcm1 mutant. AB - The original mcm1-1 mutant was identified by its inability to propagate minichromosomes in an ARS-specific manner, suggesting that it is defective in the initiation of DNA synthesis at ARSs. This mutant is also defective in expression of alpha-mating-type-specific genes. Further genetic and biochemical studies confirmed that Mcm1 is a transcription factor that mediates the transcriptional regulation of a number of genes, including genes outside of the mating type complement, by interacting with different cofactors. Although MCM1 is an essential gene, none of the previously characterized mcm1 mutants exhibits significant growth defects. To assess which of the many roles of Mcm1 is essential for growth, we constructed and characterized a temperature-sensitive conditional mutant of mcm1, mcm1-110L. This mutant exhibits a temperature dependent cell-cycle arrest, with a large, elongated bud and a single, undivided nucleus that has a DNA content of close to 2n. In addition, it shows elevated levels of chromosome loss and recombination. In spite of the severity of the mcm1 110L mutation, this mutant still retains an ARS-specific pattern of minichromosome instability. All of these phenotypes are precisely those exhibited by mutants in three MCM genes, MCM2, MCM3, and MCM5/CDC46, that have been shown to play interacting roles in the early steps of DNA replication. PMID- 1421580 TI - Signal transduction by the platelet integrin alpha IIb beta 3: induction of calcium oscillations required for protein-tyrosine phosphorylation and ligand induced spreading of stably transfected cells. AB - We demonstrate an example of signal transduction by an integrin and have begun to define the pathway through which this signaling is achieved. We constructed a stably transfected derivative of 293 cells (ATCC 1573) that expresses the platelet integrin GPIIbIIIa (alpha IIb beta 3). This cell line, clone B, adheres to and spreads on fibrinogen, a ligand for alpha IIb beta 3, while the parent cell line does not. Stimulation of these cells either by adhesion to fibrinogen or with antiserum directed against alpha IIb beta 3 results in induction of calcium oscillations, followed by tyrosine phosphorylation of at least one protein of molecular weight approximately 125 kDa. We establish that this phosphorylation, as well as the morphological rearrangements, requires the mobilization of calcium. PMID- 1421581 TI - Red storm rising. PMID- 1421582 TI - RTH Laennec: a life immersed in tuberculosis. PMID- 1421583 TI - John Keats: poet, surgeon and consumptive. PMID- 1421584 TI - First do no harm. PMID- 1421585 TI - Epidemiology of tuberculosis in Rhode Island. AB - The increase in the reported cases of tuberculosis in Rhode Island from 1985 to 1991 has been striking. This rise has occurred at a faster rate than that for the United States overall. Although the HIV epidemic is largely to blame for the resurgence of tuberculosis nationwide, its impact on tuberculosis locally has been muted. The rise in reported cases in Rhode Island is attributable mainly to increased cases among minority groups, particularly Southeast Asians. Blacks and Hispanics are likewise at an increased risk for developing active disease. Especially alarming is the dramatic rise in the number of tuberculosis cases reported in children in Rhode Island, a reflection of active disease transmission in the community. The Rhode Island Tuberculosis Control Program, already functioning at full capacity, must find ways of curbing the growing tuberculosis problem. PMID- 1421586 TI - An update on tuberculosis in children: the Rhode Island experience. PMID- 1421587 TI - Drug-resistant tuberculosis. PMID- 1421588 TI - The essentials of a tuberculosis elimination program. PMID- 1421589 TI - Screening for tuberculosis: everything you already knew, probably forgot and meant to look up. PMID- 1421590 TI - The diagnosis and treatment of active tuberculosis. PMID- 1421591 TI - Tuberculosis and the health department: the present and the future in Rhode Island. PMID- 1421592 TI - Tuberculosis in Rhode Island. PMID- 1421593 TI - Hepatic, splanchnic and systemic haemodynamic abnormalities in portal hypertension. AB - Portal hypertension is characterized by a pathological increase in portal venous pressure that leads to the formation of portosystemic collaterals that divert portal blood to the systemic circulation, bypassing the liver. Increased vascular resistance to portal blood flow is the initiating factor in portal hypertension. Increased resistance along the hepatic and portocollateral circulation is in part modifiable by pharmacological agents. An additional factor is splanchnic vasodilatation with increased portal blood inflow, which contributes to the maintenance and aggravation of the portal hypertension. Endogenous vasodilators are thought to be responsible for the splanchnic hyperaemia of portal hypertension. Vasodilatation is also prominent in the stomach and lungs, and plays an important role in the pathophysiology of portal hypertensive gastropathy and of the hepatopulmonary syndrome. The systemic circulation is markedly hyperkinetic, with reduced arterial pressure and peripheral resistance and increased cardiac output. The plasma volume is expanded due to renal sodium retention. The expanded plasma volume enables the increase in cardiac output, and represents another mechanism contributing to the increase in portal pressure. PMID- 1421594 TI - Natural history and prognosis of variceal bleeding. PMID- 1421595 TI - Emergency and elective endoscopic therapy for variceal haemorrhage. PMID- 1421596 TI - Portal hypertensive gastropathy. AB - There is now substantial clinical evidence to suggest that portal hypertensive gastropathy is an important source of gastrointestinal bleeding in patients with portal hypertension. Although a relatively uncommon presenting feature in such patients, it appears to become progressively more frequent and important the longer such patients with bleeding oesophageal varices survive after treatment by endoscopic sclerotherapy. It is now being increasingly recognized as the most important cause of haemorrhage after oesophageal varices in such patients. The endoscopic and histological characteristics of the condition are now well established but from a clinical point of view it is important to distinguish it from a number of other disorders. The pathogenesis of portal hypertensive gastropathy is poorly understood; venous congestion secondary to portal hypertension undoubtedly plays an important role but this is not thought to account entirely for the condition since abnormalities in the arterial blood supply are also observed. Many abnormalities in gastric mucosal function have been reported but it is unclear whether these are secondary disturbances or whether they play an important primary role in the development of the condition. Animal studies to date have not been helpful due to the lack of a satisfactory experimental model. Portocaval shunt surgery cures portal hypertensive gastropathy but propranolol has been shown to be highly effective in controlling haemorrhage from this condition and should now be considered the treatment of choice. The mechanism of action is unclear, and it remains to be shown whether other beta-blockers, or indeed any other drugs, are useful in treating this disorder. PMID- 1421597 TI - The role of portosystemic shunting in the management of portal hypertension. AB - In this chapter, we have tried to indicate the role of the portosystemic shunt in the treatment of portal hypertension. The conclusions are evident: in the last 10 years it has lost its role as leader in the treatment of portal hypertension. However, some firm statements can be made. The selective shunt is an operation that provides both good variceal decompression and satisfactory maintenance of liver function. Its results in great part depend on the skill of the surgeon. Only a patient with good liver function (Child's classes A and B) is a candidate for shunt surgery, with, very occasionally, a patient with severe disease (class C). In an emergency, the operation is used only after failure of sclerotherapy, but it must be used at the right time before the patient's condition has deteriorated. In the prevention of variceal rebleeding, the selective shunt or sclerotherapy can be routine measures. The choice between the two treatments depends on the patient's willingness and the ability of the institution to perform both procedures successfully. If sclerotherapy is chosen, the institution must be able to rapidly rescue a sclerotherapy failure by shunt surgery. Liver transplantation is probably the treatment of the future, but it is at present impossible to suggest that the procedure is feasible for all patients with variceal bleeding and severe liver disease. PMID- 1421598 TI - Liver transplantation in the management of bleeding oesophageal varices. PMID- 1421599 TI - Management of gastric varices. AB - Gastric varices (GV) are a common (20%) accompaniment of portal hypertension; they are more often seen in those patients who bleed than in those who do not (27% versus 4%, p < 0.01). They can develop in both segmental and generalized portal hypertension. Depending on their location and relation with oesophageal varices, GVs can be classified as gastrooesophageal varices (GOV) and isolated gastric varices (IGV); each of these can be further subdivided as follows: GOV1 (extension of oesophageal varices along lesser curve) and GOV2 (extension of oesophageal varices towards fundus); and IGV1 (varices in the fundus) and IGV2 (isolated varices anywhere in the stomach). The common presentation of GVs is variceal bleeding and encephalopathy. In comparison with oesophageal varices, GVs bleed significantly less often (64% versus 25%, p < 0.01) but more severely (2.9 +/- 0.3 versus 4.8 +/- 0.6 transfusion units, p < 0.01). Patients with GOV2 and IGV1 bleed more often than patients with other types of GVs. Sclerotherapy for oesophageal varices can significantly influence the natural history of GVs. GOV1, or lesser curve varices, disappear in the majority of cases (59%) after obliteration of oesophageal varices. In those with persisting GOV1, the incidence of bleeding and mortality is high and these patients require gastric variceal sclerotherapy (GVS). During oesophageal variceal sclerotherapy, bleeding can occasionally be induced from GVs. After obliteration of oesophageal varices, recurrence as GVs (secondary GVs) can occur in about 9% of patients. Emergency GVS is quite effective in controlling acute bleeding from GVs, more so than balloon tamponade. Potent sclerosants like tetradecyl sulphate and alcohol and a glue, bucrylate, have been quite effective. Elective GVS can achieve obliteration of GVs in nearly 70% of patients. Rebleeding and ulceration are common complications of GVS; probably related to incomplete obliteration and mucosal injury respectively. Splenectomy is quite effective in treating GVs due to segmental protal hypertension. For GV bleeding due to generalized portal hypertension, a shunt operation is often effective. TIPS procedure appear to be a very promising therapy for GV bleeding. Liver transplantation may be a superior alternative to sclerotherapy and shunt surgery for gastric varices. PMID- 1421600 TI - Transection and devascularization procedures for bleeding from oesophagogastric varices. AB - Transection and devascularization procedures (Sugiura procedure and transabdominal transection of oesophagus and devascularization) had been the most popular modality of treatment for oesophagogastric varices until the 1970s but the trends of treatment for varices have changed drastically during the last decade. This is partly due to the recent development of endoscopic sclerotherapy and partly due to the patient's increasing demand for less invasive treatment. Recently most patients with oesophagogastric varices are treated initially by endoscopic sclerotherapy and surgical treatment is only called for after sclerotherapy has failed. PMID- 1421601 TI - Pathophysiology and treatment of ascites and the hepatorenal syndrome. AB - Ascites indicates the accumulation of fluid in the peritoneal cavity, due to a wide range of causes. These causes can be classified according to the presence of portal hypertension, severe blood dyscrasia and peritoneal disease. Cirrhosis is the most frequent cause of ascites. The occurrence of ascites in cirrhosis is due to portal hypertension, which is responsible for the increase in hydrostatic pressure at the sinusoidal level and the alterations of splanchnic and systemic haemodynamics. These latter include increased splanchnic inflow, reduced systemic resistance and increased plasma volume and cardiac output. Portal hypertension also plays a major role in determining sodium retention, which occurs in the setting of increased RAA system and SNS activity. The mechanisms by which portal hypertension leads to the activation of antinatriuretic factors and sodium retention are not completely understood; three main hypotheses have been proposed to explain this relationship, namely the underfilling, the overflow and the peripheral arterial vasodilatation theories. In patients with cirrhosis and ascites, there is an overall activation of the renal prostaglandin system, which probably acts to maintain renal haemodynamics and GFR by counteracting the vasoconstricting effects of AII and noradrenaline on renal circulation. In advanced stages, ascites may become refractory to medical treatment and renal function shows a progressive impairment and eventually acute renal failure, the so-called HRS, due to a marked vasoconstriction of the renal arteries and the opening of the intrarenal-arteriovenous (A-V) shunts. In this condition, the reduced renal synthesis of vasodilating prostaglandins is probably of pathogenic importance. Treatment of ascites is usually based on bed rest, low-sodium diet and administration of aldosterone antagonists and loop diuretics. A sequential treatment of ascites based on the progressive addition of more potent drugs is the best way to relieve ascites while avoiding potentially dangerous side effects. Patients who fail to respond to the above manoeuvres are said to have refractory ascites. Current treatment of this latter condition is mainly based on therapeutic paracentesis and the application of the LeVeen shunt, but long-term results are unsatisfactory. PMID- 1421602 TI - Animal implantation results with the Utah-100 total artificial heart. AB - The Utah-100 total artificial heart was designed to have increased reliability over the Jarvik-7 total artificial heart, achieve better fit, and minimize device associated thrombus formation, without decreasing the function. The Utah-100 heart was tested in 28 calves and 3 sheep. The smallest animal at the time of implantation weighted 54 kg. Mean survival duration was 78 days (range, 1-331 days), with 14 animals surviving longer than 60 days. Multiple organ function was maintained satisfactorily with the Utah-100 artificial heart, and mean plasma free hemoglobin values in the calves that survived longer than 100 days were less than 10 mg/dl. Hemorrhage was the main cause of death in animals dying within 30 days after implantation (5/13, 38%); infection was another primary cause of death or termination (4/31, 13%). Deaths due to mechanical failure occurred from valve or diaphragm failure in two cases, yielding a 91% reliability at a 90% confidence level for 60 days' support. No animal died because of driver or other technical failure. Utah-100 hearts showed superior antithrombogenicity in the connector and valve-related areas when compared with the results of the Jarvik-7 heart, which was also fabricated and implanted in our laboratory (p less than 0.01). With these test results, the authors anticipate that the Utah-100 heart will be a safe and effective device for interim use as a bridge to heart transplantation. PMID- 1421603 TI - Vascular access surgery for maintenance hemodialysis. Variables in hospital stay. AB - Access surgery in support of maintenance hemodialysis is a major factor contributing to prolonged hospitalization in the hemodialysis patient population. In surveying 140 consecutive patients admitted for access surgery, average length of stay was 14 days, independent of race or underlying cause of renal disease. Extended length of stay was most commonly encountered in older patients admitted for thrombosed fistulae or grafts. Postoperative fever, the need for repeated femoral catheterization, delay in access revision or placement due to infection, and the need for adequate social service support resulted in prolonged hospitalization. Understanding and preventing factors that prolong hospitalization may allow the minimization of length of stay in the future and improve quality of life for the end-stage renal disease patient, while also decreasing the cost of care. PMID- 1421604 TI - Sterilization of a small caliber vascular graft with a polyexpoxy compound. AB - Sterilization of tissue based medical devices via cold sterilization processes has been limited to formaldehyde, glutaraldehyde, and mixtures of the same with alcohols and surfactants. The authors report the sterilization of a small caliber vascular graft with a combination of diglycidyl ether and ethanol. The sterilant contains 1-4% diglycidyl ether and 10-20% ethanol as an aqueous solution. Sterilization is achieved after exposure of the graft to the sterilant solution for a period of 7 days at an elevated temperature (30 degrees - 40 degrees C). The biologic indicator selected for efficacy studies was Bacillus subtilis niger ATCC 9372 (endospores). The grafts were inoculated with a concentrated endospore suspension and immersed in the sterilant solution for increasing time periods. After extensive rinsing over membrane filters to remove any residual sterilant, the grafts and filters were cultured in tryptic soy broth. D10 values were calculated using a fraction-negative, most probable number technique. Additionally, many representative bacteria and fungi were tested and found to be susceptible to the new sterilant developed. The diglycidyl ether/alcohol sterilant developed was found to be efficacious for sterilization of the tissue based vascular grafts tested. PMID- 1421605 TI - Intravascular oxygenation for advanced respiratory failure. AB - Severe acute respiratory failure of varying etiology may require the temporary use of artificial gas exchange devices. So far, extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal have been used successfully for this purpose. A totally implantable intravascular oxygenator (IVOX) recently became available. The authors have used IVOX in three patients who presented with severe respiratory failure secondary to pneumonia (n = 2) and post-traumatic adult respiratory distress syndrome (n = 1). At the time of implantation, all patients had hypoxemia (PaO2 less than 60) despite a 100% inspired oxygen concentration and forced mechanical ventilation. The duration of IVOX therapy ranged from 12 to 71 hr. All patients initially showed improvement in arterial oxygenation, allowing for moderate reduction of ventilator therapy after several hours. In one patient the pulmonary status deteriorated further, and she died from multiple organ failure despite IVOX therapy. One patient could be stabilized but died from other causes. The third patient is a long-term survivor 18 months after IVOX therapy. Gas transfer capabilities of IVOX are limited when compared to extracorporeal membrane oxygenation, and this may restrict its clinical applicability in cases of severe adult respiratory distress syndrome. However, IVOX may be used successfully in selected patients with less severe respiratory failure. PMID- 1421606 TI - In vitro and in vivo evaluation of microencapsulated porcine islets. AB - To provide a plentiful supply of pancreatic islets for future clinical transplants into diabetic patients, the authors have developed a simple and consistent method of isolation of porcine islets. Both in vitro and in vivo studies demonstrated that the islets were viable and functional. Xenotransplants of 1.5 x 10(3) - 2.5 x 10(3) of microencapsulated porcine islets into diabetic mice resulted in restoration of normoglycemia in 13 of 18 experimental animals for up to 10 months. A xenograft of 50 x 10(3) microencapsulated porcine islets into a spontaneously diabetic monkey normalized hyperglycemia for more than 150 days. This experiment indicated that the transplantation of encapsulated porcine islets has great potential as a clinical treatment in diabetes mellitus. PMID- 1421607 TI - Hybrid artificial cells: microencapsulation of living cells. AB - In 1965, the use of artificial cells for the microencapsulation of living cells was demonstrated. At that time, this technique was also proposed for use in immunoisolation of endocrine cells, islets, and hepatocytes as hybrid artificial organs. Progress in the biotechnology of cell culture in the last 10 years has allowed this approach to be extensively investigated by an increasing number of centers. The author's recent studies concentrated on microencapsulation of hepatocytes as a model system. Such cells were implanted to increase the survival of galactosamine induced fulminant hepatic failure rats, or to decrease the high bilirubin levels in Gunn rats and xenografts of microencapsulated rat hepatocytes into mice provided immunoisolation. Furthermore, hepatocyte secreted hepatic stimulating factors (mw 110,000 D) accumulating in the microcapsules helps to increase the viability of the hepatocytes. In addition to these studies, a novel, two step cell encapsulation method was developed to improve immunoisolation and biocompatibility. Microencapsulation of microorganisms was also carried out using a model microorganism to convert serum cholesterol to carbon dioxide. PMID- 1421608 TI - The high probability of a near term "cure" for type I diabetes. PMID- 1421609 TI - Cardiac pathology following resuscitative circulatory support. Direct mechanical ventricular actuation versus cardiopulmonary bypass. AB - Cardiopulmonary bypass (CPB) is currently advocated for treating refractory cardiac arrest. Direct Mechanical Ventricular Actuation (DMVA) is an alternative method that does not contact the blood and has other unique advantages for providing resuscitative circulatory support, including rapid application and relative technical simplicity. The purpose of this study was to assess pathologic changes in the heart following resuscitation with either CPB or DMVA. Dogs (n = 22) received 1 hr of CPB (n = 11) or DMVA (n = 11) following a 12.5 min cardiac arrest. All deaths [4/11 (CPB) vs. 2/11 (DMVA), p = 0.31] occurred during the initial 24 postoperative hours. At 7 days, survivors had magnetic resonance imaging to determine cardiac ejection fraction [46% (CPB) vs. 51% (DMVA), p = 0.39], as well as the presence of cardiac wall motion abnormalities [50% (CPB) vs. 33% (DMVA), p = 0.57] and gross cardiac lesions [17% (CPB) vs. 17% (DMVA)]. The survivor's hearts were then extirpated, fixed, and examined for gross lesions [2/7 (CPB) vs. 0/9 (DMVA), p = 0.17]. Transmural sections of the anterior and posterior papillary muscles were histologically evaluated. The severity and extent of epicardial fibrosis and focal myocyte necrosis did not differ between groups. These data demonstrate that DMVA does not cause more myocardial trauma than CPB when used to provide resuscitative circulatory support. Therefore, the unique attributes of DMVA may improve resuscitation outcome in patients who suffer refractory cardiac arrest, without additional risk of cardiac injury. PMID- 1421610 TI - A cerebrospinal fluid glucose biosensor for diabetes mellitus. AB - A cerebrospinal fluid (CSF) glucose biosensor is introduced. The biosensor is a polarimeter that measures the rotation of plane polarized light proportional to glucose concentration. Preliminary in vitro studies revealed a linear response with good sensitivity over a range of glucose solutions (0-400 mg/dl). Anesthetized, adult dogs underwent intravenous glucose loading, and these preliminary in vivo studies resulted in good correlation (r = 0.98) between CSF polarimeter readings and CSF glucose by laboratory assay. This in vivo correlation suggests that both mutarotation of glucose anomer and changes from other optically active substances present in CSF are either negligible or constant over the range of glucose concentrations studied. The CSF polarimeter showed a significant rise soon after the intravenous loading of glucose (1-30 min) but a longer lag time (45-60 min) between the peak blood glucose and peak CSF polarimeter reading. This preliminary work extends, to the CSF, the concept of measuring optical rotation. PMID- 1421611 TI - Quantitation of comparative thrombogenicity of dog, pig, and human platelets in a hemodialyzer. AB - Comparative platelet thrombogenicity was quantified with In111 labeled platelets. The platelets collected from the blood of Beagle dogs, Yorkshire pigs, and human volunteers were labeled with detergent free In111 tropolone, and sham hemodialysis (SHD) was performed with a hollow fiber dialyzer in a flow loop at 37 degrees C, with flow rates of 7, 150, and 270 ml/min. After SHD, hemodialyzer radioactivity was measured with an ionization chamber, gamma counter, and it was imaged with a gamma camera. The mean values of hemodialyzer-adherent platelet radioactivity were calculated. Canine platelets are more thrombogenic than porcine and human platelets. Quantitation of comparative thrombogenicity with In111 platelets may provide an estimation of prosthesis induced thrombogenicity of human platelets from animal studies. PMID- 1421612 TI - Fundamental rhythm of sympathetic nerve discharges in animals with total artificial hearts. AB - To evaluate the effect of total artificial heart replacement on the autonomic nervous system, sympathetic neurograms were analyzed by power spectrum and coherence function. Two pneumatically driven, sac type ventricular assist devices were implanted as biventricular bypasses (BVB) in adult, mongrel dogs. After initiation of BVB pumping, the natural heart was electrically fibrillated to form a BVB TAH model. Renal sympathetic nerve activity (RSNA) was recorded using a bipolar electrode attached to the left renal sympathetic nerve. RSNA was amplified and integrated by use of an R-C integrator. Power spectra of the RSNA and values of squared coherence between the arterial pressure wave form and the RSNA were calculated by computer. In animals with total artificial hearts (TAHs), coherence at the cardiac rhythm frequency was decreased, and coherence at the TAH pumping rhythm frequency was increased. These results indicate that the arterial pulse wave observed in TAH animals contributed to the sympathetic neurogram. PMID- 1421613 TI - Frequency, therapy, and prevention of infections associated with large bore catheters. AB - Since the introduction of large bore catheters for acute hemodialysis 30 years ago, many problems with handling, material, and contamination of these catheters existed. Nevertheless, the catheterization of the inferior and superior vena cavae with a large bore catheter has proved to be suitable as a rapid connection process for hemodialysis, hemofiltration, hemoperfusion, plasmapheresis, plasmaperfusion, etc. In a retrospective study with 2,626 large bore catheters in 1,627 patients, the frequency of infections, thrombosis, bleeding, and other side effects was investigated. All complications and side effects are presented dependent upon vascular access route. In total, the complication rate was 44.2% higher in subclavian puncture than in internal jugular puncture at 23.9%. The highest complication rates in both vascular access routes were infections or septicemia; infections were observed in 22.8% of subclavian catheters versus 9.5% of internal jugular catheters. Three different catheter materials (Teflon, polyurethane, and polypropylene) were investigated with scanning electron microscopy after removal. The advantages and disadvantages of the different materials are presented. PMID- 1421614 TI - Photodynamic therapy and neoplastic disease. AB - The selective photosensitization of neoplastic lesions is a new modality for eradication of early tumors and palliation of more advanced disease. There is a substantial amount of information relating to modes of photodamage, and the clinical role of this form of therapy is becoming clarified. New sensitizers are being developed with a view toward an enhanced photodynamic effect, utilization of simpler light sources, and elimination of concurrent skin photosensitization. The mechanism whereby efficacious photosensitizers localize in neoplastic, as compared with normal, adjacent tissue remains to be determined, although theories have been proposed. The photosensitizing agent used in most clinical protocols in Photofrin. This product is a complex mixture of porphyrin monomers, dimers, and higher oligomers, and interpretation of biologic and photophysical data is often difficult, although this is not universally appreciated. PMID- 1421615 TI - Pharmacodynamic and pharmacokinetic aspects of iodo-doxorubicin. AB - Iodo-doxorubicin (I-DOX) is a new doxorubicin (DOX) analog presently in phase II clinical trials in Europe. This drug is similar to DOX in its metabolism but differs in its pharmacokinetics. We describe correlations between pharmacokinetic parameters and toxicity. There is a linear relationship between the dose in mg/m2 and the nadirs of the reduction in white blood cells (WBC), neutrophils (PMN), platelets (PLT), and hemoglobin (HB). Furthermore, a linear correlation exists between the dose in mg/m2 and the area under the curve (AUC) of I-DOX. The relationship between the AUC of I-DOX and the reduction of PMNs plotted on a logarithmic scale shows a sigmoidal curve, whereas no such correlation was found between I-doxorubicinol, the major cytostatic metabolite, and the reduction in PNMs. The variation in the AUC for I-DOX correlated with the relative amount of metabolism of I-DOX. A correlation existed between the relative amount of metabolism of I-DOX and the reduction in PNMs. These results may have an impact on the evaluation of I-DOX in phase II trials, since a sound understanding of the pharmacokinetic/pharmacodynamic relationships can yield important information for minimizing unacceptable toxicity during phase II, as well as phase III, trials. PMID- 1421616 TI - Relationship between the clinical aggressiveness of large cell immunoblastic lymphomas and expression of 92 kDa gelatinase (type IV collagenase) and tissue inhibitor of metalloproteinases-1 (TIMP-1) RNAs. AB - Aberrant expression of secreted proteinases and their specific inhibitors is believed to represent an important factor in the pathogenesis of invasion and metastases of malignant neoplasms. Our previous data indicated a link between elevated expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) and the clinical aggressiveness of malignant non-Hodgkin's lymphomas. Further studies are presented on eighteen cases of high grade, large cell immunoblastic lymphoma in which expression at the RNA level of TIMP-1 and the metalloproteinase, 92 kDa gelatinase, were analyzed. Factors that may influence production of 92 kDa gelatinase, such as necrosis, vascularity, proliferative activity, and extranodal extension, as well as clinical parameters, such as age and sex, stage, location, and survival were assessed. Statistical analysis showed that, although clinical stage was the most important predictor of survival, after controlling for age at diagnosis, levels of 92 kDa gelatinase transcripts added to the ability to predict survival. PMID- 1421617 TI - O6-alkylguanine DNA-alkyltransferase is not a major determinant of sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea in four medulloblastoma cell lines. AB - The protein O6-alkylguanine-DNA alkyltransferase (O6-AGT) has been implicated as a major determinant of resistance of diverse tumors to chloroethylnitrosoureas. To evaluate the contribution of O6-AGT to resistance of medulloblastomas to chloroethylnitrosoureas, we assessed the role of O6-AGT in determining (BCNU). Sensitivity to BCNU cytotoxicity, measured as dose dependent survival of soft agar colony forming ability, varied among the lines. Two lines (UW443 and UW228 3) displayed linear survival curves and comparable BCNU sensitivity (D37 ca. 140 microM). The other lines (UW228-2 and UW228-1) had biphasic survival curves indicating that each line was composed of two sub-populations that differed in BCNU sensitivity. The D37 for these sub-populations ranged from 51 microM to 253 microM. The O6-AGT activities of the cell lines, however, did not reflect their varied susceptibilities to BCNU as evidenced by a 9-fold difference in O6-AGT activity between UW443 and UW228-3. Moreover, elimination of O6-AGT activity by the inhibitor O6-benzylguanine did not appreciably increase sensitivity to BCNU compared with the response of other human tumor cells [Dolan et al. Cancer Res. 51:3367-3372, 1991]. Our results demonstrate that O6-AGT is not a major determinant of BCNU sensitivity in the four medulloblastoma lines. PMID- 1421619 TI - Reference listings in cancer research. PMID- 1421618 TI - Catalysis and ligand binding by thymidylate synthase immobilized on thiopropyl sepharose 6B. AB - Lactobacillus casei thymidylate synthase, which employs the thiol of cysteine-198 as a covalent catalyst, was reversibly coupled to thiopropyl-Sepharose 6B through the catalytic sulfhydryl group of one of its two subunits, yielding an immobilized heterodimeric form of the enzyme possessing one free active site and one covalently modified active site. Enzyme inactivated by treatment with N ethylmaleimide, which selectively modifies the active site cysteines but not the remaining cysteines (cys-244), failed to react with the resin. Modified assay procedures were developed and utilized to characterize the activity and ligand binding properties of this unique enzymic species. The immobilized enzyme was found to catalyze thymidylate formation at its free active site but exhibited lowered specific activity (13-fold) and kcat (16-fold) values and an increased Km for dUMP (4-fold) when compared to the native, soluble enzyme. Immobilized enzyme also formed a covalent inhibitory ternary complex with 5-fluoro-2'-deoxyuridylate and 5,10-methylenetetrahydrofolate with a stoichiometry of 0.32 (mol FdUMP: mol enzyme), about half the predicted value of 0.6-0.7. The results of this initial study suggest that the active sites of the native enzyme dimer are asymmetrical in nature, and that the chemical status of the catalytic sulfhydryl groups may play a key role in directing communication between the subunits. PMID- 1421620 TI - Carpal tunnel syndrome and systemic sclerosis. AB - Carpal tunnel syndrome (CTS) was observed in 4 cases of a consecutive series of 16 patients admitted for the initial diagnosis or follow-up of systemic scleroderma from 1986 to 1990. We also observed one case of ulnar nerve compression. Neurological involvement was confirmed by electromyogram, and motor and sensory nerve conduction studies. The neurological signs appeared at the beginning of the disease in two cases and preceded the discovery of scleroderma in two. CTS is not rare in scleroderma and must be carefully sought, both clinically and electrophysiologically. Patients with 'idiopathic' CTS might need clinical follow-up for early diagnosis of scleroderma. PMID- 1421621 TI - The pustule in palmoplantar psoriasis: transformed vesicle or mature microabscess? A three-dimensional study. AB - Psoriasis on the palms and soles is characterized by pustules, vesicles and hyperkeratotic plaques. Several studies have postulated that the pustules and vesicles are round or egg-shaped. This three-dimensional study reveals that neither pustules nor vesicles have a regular spherical morphology. The vesicles are located in the upper and middle layers of the epidermis and may exhibit dumb bell- or banana-shaped lumina. The pustules consist of different compartments combining characteristics of a dyshidrotic vesicle with those of a microabscess of Munro. PMID- 1421622 TI - Nonclonal lymphocytic proliferation in cutaneous lymphoid hyperplasia: a flow cytometric and morphological analysis. AB - Cutaneous lymphoid hyperplasia, follicular B cell pseudolymphoma or lymphadenosis benigna cutis and lymphocytic infiltration of Jessner-Kanof are a group of benign lymphoid hyperplastic disorders which usually involve the skin of the face or head and neck. These lesions may be difficult to differentiate from malignant lymphocytic lymphomas both morphologically and clinically. To evaluate whether quantitative flow-cytometric analysis and DNA ploidy determination of the lymphoid cells in the lesions would provide additional and more precise diagnostic parameters, we have correlatively analyzed a case by morphological, flow-cytometric and immunohistochemical methods. The two latter methods both revealed that the lesions harbored nonclonal heterogeneous subpopulations of lymphoid cells, but 62% of the cells analyzed were of B cell lineage progenies. No pre-B cells, immature B or T determinants were detected. Ploidy analysis of the isolated lymphocytes disclosed predominantly diploid (2 N) cells with about 1% 4 N and a few (less than 5%) hyperdiploid (2.2 N) cells. Cell cycle analysis showed that 97.2% of the cells were in G0-G1 phase. Phenotyping and DNA ploidy study of the lymphocytes of the lesion may provide quantitative diagnostic parameters to distinguish this benign lesion from true lymphocytic lymphoma involvement of skin. The eventual biological behavior of the minor hyperdiploid subpopulation of lymphoid cells found in this lesion is currently uncertain, however. PMID- 1421623 TI - Wet working conditions increase brittleness of nails, but do not cause it. AB - The incidence of brittle nails is higher in women than in men. Repeatedly a suspected cause for the higher incidence of brittle nails in women is the frequent exposure to water. This study was aimed at clarifying whether wet working conditions increase the incidence of brittle nails in women and men in a similar degree. We determined the incidence of brittle nails in 511 persons in professions that involve frequent hand contact with water. The data were compared to those of a large, non-selected control group. 50% of the female probands showed the sign of brittle nails (control group: 30.4%, p less than 0.05). Only 13.5% of the male test persons of this study had brittle nails; the difference to the control group (13.2%) was not significant. It is discussed that in women the bridges between nail corneocytes are possibly weaker than in males as a constitutional characteristic. Accordingly, frequent alternating periods of hydration and drying increase the incidence of brittle nails particularly in women. PMID- 1421624 TI - Vitiligo is associated with a significant increase in HLA-A30, Cw6 and DQw3 and a decrease in C4AQ0 in northern Italian patients. AB - HLA polymorphisms of class I (HLA-A, B, C) of class II (HLA-DR, DQ) and of class III (C4A, C4B, BF) were investigated in 93 Northern Italian patients affected with vitiligo and in 388 controls. Vitiligo patients had significant increases in HLA-A30 (corrected p, pc = 0.0144), Cw6 (pc = 0.0189), DQw3 (pc less than 0.0003) and a significant decrease in C4AQ0 (pc = 0.003). Nonfamilial vitiligo is marked by increases in HLA-A30 and DQw3. Extensive vitiligo is marked by increases in HLA-A30 and Cw6. These findings suggest that immunogenetic mechanisms may be responsible for vitiligo and that unique HLA phenotypes may influence the expression of vitiligo in this population. PMID- 1421625 TI - Quinolones as an alternative treatment of chlamydial, mycoplasma and gonococcal urogenital infections. AB - We report the results of several trials aimed at evaluating the quinolones in urogenital infections. In Chlamydia trachomatis infections, ofloxacin (200 mg b.i.d. for 10 days) gave a cure rate of 98% (n = 66), and fleroxacin (400 mg s.i.d. for 7 days) provided a cure rate of 89% (n = 19). A double-blind study comparing fleroxacin (600 mg s.i.d.) to doxycycline (100 mg b.i.d.) for 7 days showed similar high cure rates for both regimens (100%; n = 23). In Mycoplasma hominis infections, ofloxacin (200 mg b.i.d. for 10 days) yielded a cure rate of 86% (n = 50) for M. hominis and 55% (n = 43) for Ureaplasma urealyticum. Gonococcal infections (n = 122) were all cured by a single dose of 200 mg ofloxacin. Both ofloxacin and fleroxacin were well tolerated and may be recommended for patients with chlamydial or uncomplicated gonococcal infections, although 600 mg fleroxacin showed a higher incidence of adverse events compared to doxycycline. PMID- 1421627 TI - Leukoderma in association with giant congenital nevi: report of two cases. AB - Two patients are presented in whom giant congenital nevi were associated with hypopigmentation. One patient has had no associated melanoma. The second patient developed hypopigmentation years before a melanoma was excised, and increased hypopigmentation was noted years later without evidence of melanoma recurrence. While the mechanism for the development of the hypopigmentation noted in these two patients in uncertain, an immunologically mediated systemic process may be responsible. PMID- 1421626 TI - Acral persistent papular mucinosis and IgA monoclonal gammopathy: report of a case. AB - The case of a 60-year-old man with acral persistent papular mucinosis (APPM), thought to represent a new distinctive form of dermal mucinosis not associated with systemic diseases, is reported. The patient had a 4-year history of multiple small papular lesions on the distal forearms, wrists and back of the hands. Histologically, mucin deposits in the upper and mid dermis sparing a superficial subepidermal grenz zone were observed. In contrast to previously described cases, a monoclonal IgA of kappa light chain isotype was detected. Our findings challenge the view that absence of paraproteinemia is a peculiar characteristic of APPM and raise once more the question of its relationship to the discrete papular form of lichen myxedematosus. PMID- 1421628 TI - Anti-lamin-B autoantibodies in a patient with cold urticaria. AB - Anti-lamin-B autoantibodies at a significant level had been found on two occasions in the serum of a 56-year-old woman who was suffering from an apparently idiopathic chronic cold urticaria. Anti-lamin autoantibodies can be detected in various autoimmune disorders including hepatitis, vasculitis and peripheral blood cytopenia. In our patient, there was no other clinical or biological abnormality. A chance association cannot be ruled out. PMID- 1421629 TI - Malignant melanoma in a Hispanic male with nevus of Ota. AB - Nevus of Ota is uncommon in the non-Oriental population. We report a case of malignant melanoma with metastasis to the genitourinary tract in a Hispanic male with nevus of Ota. Thirty-six prior cases of nevus of Ota with malignant melanoma reported in the English language are reviewed. Sixty-eight percent were women; 76% were Caucasians. Metastatic disease was reported in 16%. Three patients had liver metastases. Our case was the first involving the genitourinary tract. All but one patient with metastatic disease died within 1 month of presentation. Despite the increased frequency of nevus of Ota in the Japanese, only 4 cases of malignant melanoma have been reported. Nevus of Ota would appear to be a risk factor for developing malignant melanoma in the Caucasian population. PMID- 1421630 TI - Tripe palms: a significant cutaneous sign of internal malignancy. AB - Tripe palms is a paraneoplastic keratotic skin sign of great predictive value. It is characterized clinically by a curious rugose thickening of the palms with an accentuation of the normal dermatoglyphic ridges and sulci. Histological examination reveals an undulant epidermis with hyperkeratosis, acanthosis and papillomatosis. More than 80 cases have been reported in the literature; 90% of them were associated with an internal malignancy, mostly a carcinoma of the lung or stomach. We herein report a 66-year-old Chinese man with adenocarcinoma of the lung who presented typical tripe palms. Recognition of this distinctive pattern should prompt a meticulous search for an underlying malignancy, particularly lung or gastric carcinoma. PMID- 1421631 TI - Hair follicle nevus. AB - We present a case of hair follicle nevus, a rare hamartoma composed of vellus hair follicles. Hair follicle nevus should be differentiated from accessory auricle, trichofolliculoma and hair nevus. PMID- 1421632 TI - Annular psoriasiform eruption with lymphocytic infiltration of the epidermis: a variant of acute psoriasis? AB - Disseminated annular psoriasiform lesions developed over a period of 2 months in a 48-year-old man with no preceding psoriatic history of drug intake, being accompanied by general dullness and arthralgia. Etretinate was effective for both skin eruption and arthralgia; only the latter recurred on its cessation 5 months later. However, histologic features examined by serial sections totally lacked those of pustular psoriasis; there were no neutrophils in the epidermis where massive T lymphocyte infiltration existed instead, in a fashion similar to that of early psoriatic lesions. We differentiated this peculiar annular psoriasiform eruption from the annular erythematous lesions noted in pityriasis rosea, erythema annulare centrifugum, subacute cutaneous lupus erythematosus, annular erythema associated with Sjogren's syndrome and erythema chronicum migrans. It is our speculation that this dermatosis represents a variant of acute psoriasis, rather than annular pustular psoriasis. The histopathologic and immunohistologic findings suggest ongoing cellular immune responses in these lesions where some unknown inhibitory mechanisms might be operative against further production of neutrophil chemotactic factors that usually takes place in psoriatic lesions. PMID- 1421633 TI - Chilblain lupus erythematosus and lupus pernio--the same entity? PMID- 1421634 TI - Acral persistent papular mucinosis and lichen myxedematosus. PMID- 1421635 TI - Psoriatic alopecia: acute and chronic hair loss in 47 patients with scalp psoriasis. AB - Symptomatic hair loss and alopecia were seen in psoriatic lesions of the scalp in 47 patients. Remarkably, in 66% of the cases it was an inaugural manifestation, and in 36% the scalp was exclusively involved. Therefore 34% of the patients presented with a primary manifestation of isolated scalp psoriasis. Hair loss varied in intensity from protracted to moderate and massive (36% in tufts). It presented as acute (51%), chronic (36%) or chronic recurrent (13%). Thirteen patients (28%) became aware of the hair loss with the beginning of therapy. The alopecia was found to be circumscribed in 75% of the cases and diffuse in 25%. In 2 cases psoriatic alopecia also manifested itself at sites other than the scalp. The telogen count was found to be increased up to 25-86% in the florid stage. Examinations under the light microscope showed a patchy perifollicular lymphohistiocytic infiltrate in the upper and middle dermis with adnexotropia in several cases. This infiltrate can alter the follicle epithelium and may lead to a granulomatous foreign-body reaction with destruction of the hair follicle. After topical antipsoriatic treatment, most of the reexamined patients showed complete hair regrowth, while 5 developed a residual scarring. Therefore, in the patient with circumscribed or diffuse symptomatic alopecia, with or without scarring, psoriatic alopecia should be considered. PMID- 1421637 TI - Relation between urinary albumin excretion and skin involvement in patients with psoriasis. AB - The increase in urinary albumin excretion rate (AER), a hallmark of both diabetic nephropathy and hypertension, has also been described in patients affected with diffuse psoriasis. The aim of this study was to investigate whether such an increase is independent of the coexistence of diabetes or hypertension and whether it may be related to the extension and severity of skin lesions. Median AER, determined by radioimmunoassay, was significantly higher in a group of 32 normotensive nondiabetic psoriatic patients than in 36 age- and sex-matched controls (9.6 vs. 5.3 micrograms/min; p = 0.0006). AER was related with grading of skin involvement (r = 0.65; p = 0.001); patients with the most widespread skin lesions (psoriasis area and severity index: PASI greater than 11) were characterized by a significantly raised median AER (14.9 micrograms/min) compared with those with PASI scores between 4 and 11 (9.8 micrograms/min) or less (5.6 micrograms/min) and controls (F = 10.58; p = 0.0001), independent of other covariates such as age, sex and blood pressure (p = 0.001). This latter finding was confirmed by the prevalence of microalbuminuria (AER greater than 10 micrograms/min) which was present in 2 out of 8 patients with PASI less than 4, 0 out of 12 patients with PASI ranging between 4 and 11 and in 5 out of 12 psoriatics with PASI greater than 11 (p = 0.038 by two-tailed Fisher's exact test). PMID- 1421636 TI - Correlation of eosinophils, eosinophil cationic protein and soluble interleukin-2 receptor with the clinical activity of atopic dermatitis. AB - To evaluate the correlation with the clinical activity of atopic dermatitis (AD) we investigated prospectively cellular and serological parameters such as eosinophils, eosinophil cationic protein (ECP), soluble IL-2 receptor (sIL-2R), soluble CD23 (sCD23) and lactate dehydrogenase (LDH) in peripheral blood of 37 AD patients on admission to and discharge from the Department of Dermatology at the University Hospital in Zurich. On admission the actual clinical skin condition as measured by the skin intensity score (SIS) was significantly correlated with eosinophils (p less than 0.005), ECP (p less than 0.05) and sIL-2R (p less than 0.001). During the observation period a significant improvement in the clinical status as measured by the SIS was observed in all AD patients (p less than 0.001). A significant decrease in sIL-2R (p less than 0.005), which was most pronounced in the group of AD patients receiving systemic steroids, together with a decrease in eosinophils and ECP but not in sCD23 and LDH could be demonstrated between admission and discharge. In addition, a slight but significant increase in peripheral blood lymphocytes (p less than 0.005) and monocytes (p less than 0.01) was noted. Comparing the 'extrinsic' (n = 32) and the 'intrinsic' (n = 5) types of AD no significant differences with regard to the above mentioned parameters were found. Our data indicate that cellular and serological parameters such as eosinophils, ECP and sIL-2R reflect the clinical activity of AD and may therefore give further insights into the pathogenesis of this disease. PMID- 1421638 TI - Plasma lipid changes in psoriatic children. AB - Plasma lipid, lipoprotein and apoprotein concentrations were determined in psoriatic children and in healthy controls. The plasma total cholesterol (TC) was higher than in controls (p = 0.03). The higher cholesterol levels were explained by an almost significant increase in cholesterol associated with high-density lipoproteins and by the tendency towards higher values of cholesterol associated with low-density lipoproteins and very-low-density lipoproteins. No significant changes of plasma triglycerides were observed. Levels of apoproteins (apo) AI and apo B were not significantly different in psoriatic children; however, the levels of apo B were correlated differently with plasma TC in psoriatic children, and the ratio TC/apo B was significantly increased in patients with respect to the controls, suggesting some differences of plasma lipoprotein lipid/apoprotein relationship in psoriasis. PMID- 1421639 TI - Prediction of glomerular filtration rate using aminoglycoside clearance in critically ill medical patients. AB - OBJECTIVE: The aim of this preliminary investigation was to evaluate the use of aminoglycoside serum concentrations as a surrogate measure of the glomerular filtration rate (GFR) in comparison with other measured and empiric methods against inulin, the criterion standard measure of GFR. DESIGN: A consecutive sample of all eligible patients. SETTING: An eight-bed medical intensive care unit in a university-affiliated tertiary-care teaching hospital. PATIENTS: Ten critically ill medical patients receiving gentamicin or tobramycin for presumed or documented gram-negative bacillary infection were enrolled in the study. The patients were mechanically ventilated and had underlying organ system dysfunction. All ten patients completed the study. INTERVENTION: Patients underwent renal functional assessment by measured inulin (Cl(in)) and 24-hour urinary creatinine clearance (Clcr). Aminoglycoside serum concentrations were used to estimate GFR and were compared with the two measured methods and a creatinine clearance calculated with the Cockcroft-Gault method (ClCG). All evaluations were performed the same day. RESULTS: Cl(in) averaged 51.6 +/- 35.0 mL/min and serum creatinine ranged from 0.3 to 5.4 mg/dL (26.5 to 477.3 mumol/L). Steady-state peak and trough aminoglycoside concentrations were 6.1 +/- 1.4 and 1.3 +/- 0.9 micrograms/mL, respectively. There were no statistically significant differences between the various methods, although the aminoglycoside-calculated GFR (Cl(amg)) 95 percent confidence intervals were smaller than Clcr and ClCG compared with Cl(in). Mean absolute errors were smaller with Cl(amg) than with Clcr and ClCG. Regression results indicated that only Cl(amg) and ClCG demonstrated agreement with Cl(in) (lines not different from y = x). However, the Cl(amg) showed closer agreement, with a mean square error almost half that of ClCG (9.6 vs. 18.1). CONCLUSIONS: Cl(amg) can be used routinely as an estimate of GFR in critically ill patients, with less error than empiric methods. PMID- 1421641 TI - Evaluation of glipizide and glyburide in a health maintenance organization. AB - OBJECTIVE: To determine if there was a difference in the long-term glycemic control, average daily dose, and cost of therapy in patients with noninsulin dependent diabetes mellitus (NIDDM) treated with glyburide and glipizide in a health maintenance organization (HMO). DESIGN: Retrospective evaluation of medical and pharmacy records. SETTING: Multispecialty group practice HMO. PATIENTS: 140 NIDDM patients being treated with either glyburide (n = 70) or glipizide (n = 70) were randomly selected from the populations of patients receiving either drug using computerized pharmacy records. MAIN OUTCOME MEASURE: Mean daily doses and blood glucose measurements (fasting blood glucose, random blood glucose, hemoglobin A1C) were stratified in 3-month periods from the time the drug therapy was started or the patient first presented to the clinic for a total of 18 months. Long-term glycemic control was defined as fasting blood glucose less than 8.33 mmol/L (150 mg/dL). RESULTS: The groups were comparable with regard to age (53.4 y glyburide, 56.7 y glipizide), gender (43 M:27 F glyburide, 47 M:23 F glipizide), race (38 W/16 B/16 H glyburide, 45 W/16 B/9 H glipizide), concurrent medical conditions, adverse effects, and compliance. Long term glycemic control was similar in both groups. Although the number of subjects who were controlled (by definition) tended to be greater in the glyburide group, no clinical or statistical difference was found. There was no statistical difference in mean daily dose between the ethnic groups, but the small numbers preclude further analysis. The glipizide group had a larger percentage increase in dose within the first year than did the glyburide group; however, the percentage increase from the 3-month dose was similar after 18 months (22.7 percent glyburide, 27.5 percent glipizide.) Average daily cost of therapy, based on mean daily dose, was slightly lower for glyburide-treated patients. CONCLUSIONS: If glycemic control is similar with glyburide and glipizide, as seen in this study, economic considerations regarding choice of therapy and formulary inclusion may be appropriate. PMID- 1421640 TI - Heparin and infusion phlebitis: a prospective study. AB - OBJECTIVE: To determine whether heparin sodium, when added to fluids infused through a peripheral catheter, reduces some local catheter-related problems (i.e., phlebitis, catheter obstruction, and extravasation of fluid) and extends the catheter's useful life. DESIGN: Prospective, double-blind, placebo controlled. SETTING: Internal medicine ward of a general hospital with 400 beds. PATIENTS: Eighty-one consecutive acute collaborating patients who had a venous catheter in the forearm, inserted by nurses with more than one year of professional experience. INTERVENTION: Heparin sodium 1000 units/mL or NaCl 0.9% was added to compatible infusion fluids just before they were given to the patients. The final concentration of heparin was 1 unit/mL. MEASUREMENTS: Length of time until catheters were removed and reasons for their removal. RESULTS: The heparin group had a lower rate of local catheter-related problems than the placebo group (34.3 vs. 61.5 percent, respectively, p less than 0.05; 95 percent confidence interval for the difference 4.3 to 50.1 percent). The catheter's mean life in the heparin group was longer than that of placebo group (98.9 +/- 55.2 vs. 66.2 +/- 47.2 h, respectively, p less than 0.05; 95 percent confidence interval for the difference 9.15 to 56.25 h). This effect was mainly attributable to prevention of noninflammatory catheter-related problems (e.g., obstruction, extravasation) and to a delay in the appearance of phlebitis. CONCLUSIONS: Heparin sodium, when added to infusion fluids to a final concentration of 1 unit/mL, diminishes local intravenous catheter-related problems and extends the catheter's life. PMID- 1421642 TI - Compatibility of ceftazidime and aminophylline admixtures for different methods of intravenous infusion. AB - OBJECTIVE: Aminophylline and ceftazidime are sometimes used concurrently in patients with respiratory disorders. Parenteral aminophylline usually is administered as a constant infusion, and ceftazidime is given intermittently or less commonly as a constant infusion. We evaluated the stability and compatibility of the two drugs when aminophylline is given as a constant intravenous infusion and ceftazidime is administered simultaneously either through a y-site (piggyback method) or as a continuous infusion (constant infusion method). DESIGN: The chemical stability of intravenous aminophylline and ceftazidime in dextrose 5% and NaCl 0.9% for both methods was studied. Three different formulations of ceftazidime from the same manufacturer were studied (minibag using reconstituted ceftazidime, premixed minibag, and ceftazidime arginine). For the piggyback and constant infusion methods, samples were collected at 0, 1, and 2 hours; and 0, 6, and 24 hours, respectively. All experiments were conducted in triplicate. Samples were analyzed in duplicate by a stability-indicating HPLC assay method. OUTCOME MEASURE: Ceftazidime and aminophylline were considered stable if concentrations remained above 90 percent of the original concentrations over the time periods studied. RESULTS: Ceftazidime was determined to be compatible with aminophylline in the piggyback method. In contrast, when aminophylline and ceftazidime were admixed in the same intravenous container (constant infusion method), the two drugs were not stable. CONCLUSIONS: These data indicate that aminophylline and ceftazidime admixtures are incompatible when prepared in the same intravenous container, which may occur if both are given as a constant infusion. The two drugs are compatible when the ceftazidime is piggybacked into a primary intravenous set in which aminophylline is administered as a constant infusion. PMID- 1421643 TI - Two cases of suspected immunologic-based hypersensitivity reactions to etoposide therapy. AB - OBJECTIVE: To report two cases of suspected immunologic-based hypersensitivity reactions to etoposide therapy. DATA SYNTHESIS: Two cases are presented that differ from the majority of reported hypersensitivity reactions to etoposide. One patient, who tolerated etoposide during his first three-day chemotherapeutic dosage regimen, developed a hypersensitivity reaction to etoposide upon re exposure to the drug during the first day of a subsequent three-day cycle. Another patient experienced a hypotensive episode on the first day of an initial three-day regimen, which did not recur on the two subsequent days of the cycle. However, when the patient was re-exposed to etoposide four weeks later, he experienced a severe reaction within minutes of drug infusion. Both patients were premedicated with corticosteroids and neither reported prior drug allergies. CONCLUSIONS: Based upon these cases and other literature reports, we believe these reactions primarily represent a type II or immunologic-based hypersensitivity reaction to etoposide. PMID- 1421644 TI - Cephalexin-induced Stevens-Johnson syndrome. AB - OBJECTIVE: To report a case of cephalexin-induced Stevens-Johnson syndrome (SJS), a devastating adverse drug reaction that involves the entire skin surface and mucosal areas of the body. DATA SOURCES: MEDLINE search (key terms cephalosporins, Stevens-Johnson syndrome, erythema multiforme, and systemic lupus erythematosus) and references identified from bibliographies of pertinent articles. DATA SYNTHESIS: Clinical presentation and manifestations of SJS include the skin, eyes, gastrointestinal tract, and pulmonary system. Infectious complications are the leading cause of mortality. Early intervention is important to prevent progression of SJS. The case described is consistent with the features of this syndrome. The patient presented with fever, arthralgias, and malaise. Skin lesions included a diffuse violet macular rash with erythema and multiple bullous lesions on her neck and abdomen. The skin biopsy was consistent with SJS. Multiple mucocutaneous ulcers were found in her mouth, but no evidence of lower gastrointestinal tract involvement was documented. She remained relatively free of pulmonary complaints except for the presenting bronchitis. CONCLUSIONS: Cephalexin should be added to the list of agents to consider as iatrogenic causes of SJS. PMID- 1421645 TI - Acute renal failure in an elderly woman following intramuscular ketorolac administration. AB - OBJECTIVE: To report a case of ketorolac tromethamine-induced acute renal failure and to discuss the risk factors that make patients more susceptible to the renal effects of nonsteroidal antiinflammatory drugs (NSAIDs). DATA SOURCES: Case reports and review articles identified by MEDLINE. Indexing terms included ketorolac, renal failure, and NSAIDs. DATA EXTRACTION: Data were abstracted from pertinent published English-language sources and were reviewed by all authors. DATA SYNTHESIS: Ketorolac is an intramuscularly administered NSAID with many of the same adverse effects associated with other oral NSAIDs. Although reversible depression of renal function has been associated with several NSAIDs, to date there have been no published reports of acute renal failure secondary to ketorolac administration. A 71-year-old woman received three doses of ketorolac to control the pain associated with pelvic and T11-T12 compression fractures. Over the next two days, the patient developed signs and symptoms of acute renal failure, including significant increases in blood urea nitrogen, serum creatinine, and peripheral edema. These signs and symptoms resolved over the next three to four days. Certain risk factors, several of which were present in this woman, make individual patients more susceptible to the renal affects of NSAIDs. These risk factors include advanced age, cirrhosis, volume depletion, congestive heart failure, gastrointestinal bleeding, and preexisting mild renal dysfunction. CONCLUSIONS: Caution should be taken when initiating ketorolac or any NSAID therapy with specific attention to risk factors that predispose a patient to renal dysfunction. PMID- 1421646 TI - Anaphylactoid reaction following ketorolac tromethamine administration. AB - OBJECTIVE: To report a case of an anaphylactoid reaction to injectable ketorolac tromethamine in a patient with no prior history of allergies or risk factors associated with nonsteroidal anti-inflammatory drug-induced hypersensitivity reactions. CASE SUMMARY: A 37-year-old man without a significant medical history presented to an emergency department with vague, dull, left-sided chest pain. Myocardial infarction was ruled out based on an unremarkable electrocardiogram, chest X-ray, and laboratory data that were within normal limits. Sublingual nitroglycerin 0.4 mg, magnesium/aluminum hydroxide gel 30 mL, and intravenous ranitidine 50 mg were administered without resolution of symptoms. Ketorolac tromethamine 60 mg was administered intramuscularly with resolution of symptoms. The patient was discharged; however, within 30 minutes, he returned to the emergency department with facial swelling, shortness of breath, and chest tightness. Multiple doses of aerosolized albuterol and intravenous methylprednisolone and diphenhydramine were administered, resulting in a slight improvement of symptoms. The patient was admitted for a complete cardiac evaluation that proved negative. The allergic symptoms resolved and the patient was discharged without medication after a three-day hospitalization. DISCUSSION: Ketorolac tromethamine is the first injectable nonsteroidal antiinflammatory drug approved for short-term pain management. A review of the literature revealed no similar cases of anaphylactoid reaction. CONCLUSIONS: Healthcare professionals must be aware of the potential risks of anaphylactoid reactions, especially in light of the increased use of injectable ketorolac in the ambulatory setting and availability of the oral formulation. PMID- 1421647 TI - Methemoglobinemia in a patient undergoing gastrointestinal endoscopy. AB - OBJECTIVE: To report a case of methemoglobinemia induced by benzocaine in a patient undergoing gastrointestinal endoscopy. CASE SUMMARY: Before undergoing an upper gastrointestinal endoscopy, a 15-year-old girl received 20% benzocaine as a spray, to locally anesthetize the pharyngeal mucosa. Thirty minutes after the endoscopy, the patient suddenly became cyanotic, short of breath, and comatose. She was intubated and transferred to the intensive care unit. Her blood methemoglobin concentration was 54 percent. The patient was treated with intravenous methylene blue. Four hours later she was extubated. She was alert, awake, and asymptomatic. DISCUSSION: This is the fourth reported case of methemoglobinemia induced by benzocaine spray in patients undergoing gastrointestinal endoscopy. Pathways for the formation of methemoglobin in the body are reviewed. Intravenous methylene blue is the drug of choice for this condition, and produces rapid and dramatic reversal of methemoglobinemia. CONCLUSIONS: It is common to use benzocaine spray prior to upper gastrointestinal endoscopy. Benzocaine rarely induces methemoglobinemia in these patients. Prompt diagnosis and treatment with intravenous methylene blue is warranted in such cases. PMID- 1421648 TI - Cloxacillin-induced acute tubulo interstitial nephritis. AB - OBJECTIVE: To report a case of possible cloxacillin-induced acute tubulo interstitial nephritis (AIN). CASE SUMMARY: A 15-year-old male patient presented with hypertension, edema, lumbar pain, sterile pyuria, eosinophiluria (ten percent), and severe renal dysfunction three months after the ingestion of cloxacillin. A renal biopsy revealed diffuse edema and inflammatory infiltrate of the interstitium (five percent eosinophils). He received four sessions of peritoneal dialysis with dramatic improvement in urinary output and renal function. His biochemical parameters returned to normal values 21 days after admission, without the use of glucocorticosteroids. DISCUSSION: Published case reports on AIN induced by penicillin and related drugs are reviewed and compared. The role of interstitial edema in acute renal failure associated with drug induced AIN is mentioned. CONCLUSIONS: AIN is a rare but significant complication of therapy with penicillin and related drugs. The clinical picture is similar for all of these drugs, but skin rash and fever are absent in AIN induced by cloxacillin and cloxacillin-related drugs. Dialysis improved the patient's urinary output and renal function. Beta-lactam antibiotics should be avoided in patients with cloxacillin-induced AIN. PMID- 1421649 TI - Chlorpropamide-induced hyponatremia in the veteran population. AB - OBJECTIVE: To determine the incidence and possible risk factors associated with chlorpropamide (CPA)-induced hyponatremia in the veteran population. DESIGN: Retrospective cohort study. SETTING: Federal tertiary care medical center. PATIENTS: Veterans receiving CPA from our facility with at least one serum sodium concentration below 135 mmol/L within the past year were eligible. A randomly selected control group consisting of patients taking CPA with normal sodium concentrations was also chosen. One hundred forty-five of 799 patients who had received CPA were included in the study. RESULTS: The average daily dose of CPA was 425 +/- 207 mg (+/- SD). The incidence of hyponatremia associated with CPA was 7.1 percent (57/799 patients). The majority of patients were mildly hyponatremic (48/57 patients, 84 percent) with serum sodium concentrations between 130 and 134 mmol/L. The incidence of CPA-induced syndrome of inappropriate antidiuretic hormone was 2.1 percent. Concurrent angiotensin converting enzyme (ACE) inhibitor use was identified as a risk factor; thiazide diuretic use was not. CONCLUSIONS: The incidence of hyponatremia related to CPA use in elderly veterans is consistent with other reports in the literature. ACE inhibitors may be a predisposing factor for CPA-induced hyponatremia. PMID- 1421650 TI - Use of metered-dose inhalers in mechanically ventilated patients. PMID- 1421651 TI - Buspirone in obsessive-compulsive disorder. PMID- 1421652 TI - Danazol in hereditary angioedema. PMID- 1421653 TI - Pamidronate. AB - OBJECTIVE: The primary objective of this article is to introduce readers to the use of a new agent, pamidronate. The article discusses its use in hypercalcemia of malignancy (HCM), osteolytic lesions, and Paget's disease. Pharmacokinetic data and clinical trials are reviewed, as well as adverse effects and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify English-language studies involving pamidronate for the period from 1970 to 1992. STUDY SELECTION: As comparative trials were few in number, trials using pamidronate as a single agent were also reviewed. DATA EXTRACTION: Sparse pharmacokinetic data were obtained from clinical trials. All clinical trials available at the time of publication that met the following criteria were reviewed: (1) allowed for adequate rehydration prior to drug therapy; (2) reported standardized and corrected serum calcium concentrations; (3) separated data obtained from patients who received pamidronate alone from those who received pamidronate and concurrent chemotherapy. RESULTS: Pamidronate has a pharmacologic profile similar to that of etidronate, but pamidronate is more potent and has a longer duration of effect. It has been investigated primarily in the treatment of HCM as well as in the treatment of osteolytic bone metastases and Paget's disease. In hypercalcemia of malignancy it appears to be as effective as established agents with the advantage that a single dose of pamidronate 90 mg iv provides a durable response. In Paget's disease chronic oral administration has also been shown to be effective in relieving bone pain. Adverse reactions with intravenous administration are transient and self-limiting and usually occur with the first dose. The most common adverse effect is a transient and self-limiting fever. Chronic oral administration of doses greater than 600 mg/d is associated with gastrointestinal toxicities. CONCLUSIONS: Although more well-designed clinical trials comparing pamidronate with standard therapies and other available agents are necessary, initial results indicate that pamidronate is an effective and promising alternative for use in the treatment of HCM. PMID- 1421654 TI - Adjuvant intravesical therapy for superficial bladder cancer. AB - OBJECTIVE: To review the results of clinical trials and adverse drug effects of thiotepa, BCG vaccine, mitomycin, and doxorubicin, which are used as adjuvant intravesical therapy for superficial bladder cancer. DATA SOURCE: Information was retrieved from a MEDLINE search, of the English-language literature. Indexing terms included adjuvant pharmaceutics, bladder neoplasms, thiotepa, mitomycin, BCG vaccine, and doxorubicin. DATA EXTRACTION: Data from several human and in vitro studies were assessed and evaluated, according to the strength of comparative data and therapeutic response. STUDY SELECTION: Emphasis was placed on clinical trials that assessed and evaluated dosage, therapeutic regimens, and therapeutic response of adjuvant intravesical therapy for superficial bladder cancer. DATA SYNTHESIS: Adjuvant intravesical therapy and long-term prophylaxis are effective for superficial bladder cancer. Studies have shown that doxorubicin, thiotepa, BCG, and mitomycin, when used as adjuvant therapy, provide better protection than transurethral resection alone against tumor recurrence and prolong the time to when cystectomy is required. CONCLUSIONS: Several randomized clinical trials suggest that BCG is superior to thiotepa, doxorubicin, and mitomycin in preventing bladder tumor recurrence and tumor progression. Local cystitis is an adverse effect produced by all four agents; however, BCG vaccine has been reported to cause a higher incidence of adverse reactions (e.g., dysuria, hematuria). BCG may also cause an influenza-like syndrome, arthralgias, and fever, but most of these reactions have resulted in few severe adverse effects when the drug is given in the relatively modest recommended doses. PMID- 1421655 TI - Lactulose in the management of constipation: a current review. AB - OBJECTIVE: To review the current published clinical studies evaluating the clinical efficacy and safety of lactulose compared with other laxatives or placebo. Adverse effects associated with lactulose are also reported. DATA SOURCES: Information was retrieved by searching the MEDLINE and EMBASE databases for clinical trials, abstracts, conference proceedings, and review articles dealing with lactulose. STUDY SELECTION: Emphasis was placed on clinical trials where lactulose was compared with other laxatives or placebo in patient populations where the diagnosis of constipation was reasonably established. DATA EXTRACTION: The methodology and results from clinical studies were evaluated. Assessment of the studies was made based on diagnosis of constipation, prior management of patients, follow-up of patients, dosage, and adverse effects. DATA SYNTHESIS: Clinical trials in geriatric patients, terminally ill patients, children, and normal and constipated subjects were reviewed. In most instances, lactulose was compared with a placebo, without incorporating the current education on dietary techniques for improving defecation. CONCLUSIONS: Generally, clinical trials have demonstrated a beneficial response compared with placebo, although sometimes that response has been only marginally better, from a clinical point of view. PMID- 1421656 TI - Impact of therapeutic drug monitoring of intravenous theophylline regimens on serum theophylline concentrations in the medical intensive care unit. AB - OBJECTIVE: The primary objective of this study was to determine if a clinical pharmacist ensuring appropriate use and performing careful pharmacokinetic analysis of serum theophylline concentrations (STCs) can result in optimal theophylline regimens for patients in a medical intensive care unit (ICU). DESIGN: In phase 1 of the study, housestaff physicians determined the theophylline dosing regimen. A clinical pharmacist prospectively followed these initial patients, but did not intervene. Patients in phase 2 received intravenous theophylline, with all dosing regimens being based on prospective therapeutic drug monitoring (TDM) by a clinical pharmacist. PARTICIPANTS: The first phase enrolled 11 consecutive patients admitted into the medical ICU and requiring intravenous theophylline. This was followed by a second phase of 14 medical ICU patients whose intravenous theophylline regimen was determined by a clinical pharmacist performing pharmacokinetic analysis. MAIN OUTCOME MEASURES: Questions were organized into the following sections: (1) number of STC blood samples drawn, (2) number of emergency STCs performed, (3) number of concentrations per infusion-rate changes, (4) number of STC results in the pharmacist-generated regimens that were within the physicians' predetermined acceptable range. RESULTS: In phase 1, 27 theophylline rate changes occurred, with a mean +/- SD of 1.01 +/- 0.3 STCs per day. In phase 2, 44 theophylline infusion rates were changed, with a mean +/- SD of 0.62 +/- 0.3 STCs per day. The TDM group had a significant reduction (p less than 0.001) in inappropriate concentrations (15 vs. 40 percent) as set by predetermined criteria, and fewer emergency theophylline concentration requests (2 vs. 14). Serum theophylline concentrations ordered by the physician were achieved in 85 percent of the pharmacist-generated regimens. CONCLUSIONS: Pharmacokinetic analysis when performing TDM in the determination of intravenous theophylline regimens can result in optimal therapy for patients, while significantly reducing the number of STCs required. PMID- 1421657 TI - Antibiotic use in urban whites and blacks: the Minnesota Heart Survey. AB - OBJECTIVE: To assess racial differences in the use of antibiotics, including penicillins, erythromycins, tetracyclines, sulfas, and cephalosporins. DESIGN: Population-based surveys, conducted from 1985 to 1987. SETTING: The seven-county metropolitan area of Minneapolis-St. Paul, MN. PARTICIPANTS: 3127 whites (response rate 68 percent) and 1047 blacks (response rate 65 percent), aged 35-74 years. RESULTS: White women (26 percent of 1625) were more likely to report having taken an antibiotic in the past year than were white men (18 percent of 1502), black women (18 percent of 590), or black men (15 percent of 457). Reported antibiotic usage decreased with increasing age. Black men were more likely than white men to report the use of tetracyclines or sulfas; otherwise, white men reported higher usage prevalences. White women reported higher usage prevalences of all drug classes than black women. CONCLUSIONS: Significant independent predictors of antibiotic use were younger age, white race, and female gender. Potential explanations for these differences include differences in patient access, physician-prescribing behaviors, or both. PMID- 1421658 TI - Professional self-image among Israeli pharmacists: sectoral differences. AB - OBJECTIVE: To examine sectoral differences in the professional activities and self-images of Israeli pharmacists. DESIGN, SETTING, AND PARTICIPANTS: Pharmacists from private, community, and hospital sectors (n = 145) completed a survey that assessed the rewards accrued from their professional activities as pharmacists and evaluated their professional and sectoral self-image. RESULTS: Few intersectoral differences were found among Israeli pharmacists. Most agreed that the main rewards in the public sector are secure employment, intellectual challenge, and responsibility. In the private sector, the rewards are high income, responsibility, and opportunity to counsel. The majority of pharmacists in all sectors are satisfied with their profession, and 90.7 percent would choose it again. Nevertheless, they ranked pharmacy eighth among nine professions chosen for comparison, which shows quite a low professional image. The private and hospital pharmacists attributed a higher social status to their own sectors than to the community sector. CONCLUSIONS: The inferior professional self-image held by pharmacists, despite the rewards of the profession, should be examined in greater detail. PMID- 1421659 TI - Potential fluoxetine-selegiline interaction. PMID- 1421660 TI - Possible theophylline-minocycline interaction. PMID- 1421661 TI - Initiating clinical pharmacokinetics in China. PMID- 1421662 TI - Therapeutic monitoring of theophylline--a real need! PMID- 1421663 TI - Comment: patterns of isotretinoin prescribing. PMID- 1421664 TI - Comment: lovastatin-induced rhabdomyolysis in the absence of concomitant drugs. PMID- 1421665 TI - Aerosolized pentamidine and Pneumocystis carinii pneumonia: patient compliance and outcomes. AB - OBJECTIVE: The study objectives were to compare compliance between every-two-week and every-four-week aerosolized pentamidine regimens, and to determine if patients who were more compliant with the use of aerosolized pentamidine were at decreased risk for developing Pneumocystis carinii pneumonia (PCP). DESIGN: Nonrandomized observational study of patients receiving aerosolized pentamidine for PCP prophylaxis using the hospital pharmacy computer system to document aerosolized pentamidine use and compliance, and the Patient Administration Division's computer to document cases of PCP. SETTING: Tertiary care, US Army medical center. PATIENTS: All patients who were prescribed aerosolized pentamidine (60 mg every two weeks, 300 mg every four weeks, or both) over a 3.5 year period. MAIN OUTCOME MEASURES: Mean percent compliance was determined and compared between every-two-week and every-four-week regimens. The relationship between compliance and cases of PCP as determined using nonparametric statistics. RESULTS: Patients (n = 146) who were prescribed aerosolized pentamidine 60 mg every two weeks were more compliant (p = 0.006) than those prescribed 300 mg every four weeks. In addition, those patients who initially received the 60-mg regimen and were switched to the 300-mg regimen were more compliant when taking the 60-mg dose (p = 0.027). There was no association between compliance with either regimen and cases of PCP. Compliance generally was poor with both regimens. CONCLUSIONS: Patients on every-two-week regimens of aerosolized pentamidine were more compliant than those on every-four-week regimens. However, regardless of compliance, some patients failed aerosolized pentamidine over the 3.5-year period. Other agents that lend themselves to compliance may be more appropriate for PCP prophylaxis than aerosolized pentamidine. PMID- 1421666 TI - Setting confidence intervals for drug concentrations from pharmacokinetic parameters. AB - OBJECTIVE: To describe and illustrate a convenient method of forecasting drug concentrations with confidence intervals (CIs) using the means and standard deviations of relevant pharmacokinetic parameters (e.g., clearance and volume of distribution). DESIGN: Using summary statistics from previously published reports, a Monte Carlo technique employing a SAS random number generator creates an arbitrarily large "sample" of each pharmacokinetic parameter. A related "sample" of drug concentrations is provided by inserting the parameters into the appropriate model. A point estimate of the mean drug concentration with a CI is calculated using standard statistical methods. Both the one- and two-compartment body models are illustrated using previous investigations of gentamicin and lidocaine, respectively. RESULTS: One-compartment simulations describe CIs for gentamicin concentrations that vary widely depending on the source of the clearance and volume of distribution parameters. Lidocaine CIs using a two compartment analysis indicate a range of concentrations quite different from the expected mean. CONCLUSIONS: CIs provide a perspective of drug therapy that is considerably more informative than a simple point estimate of the mean concentration. PMID- 1421667 TI - Lack of in vitro inactivation of tobramycin by imipenem/cilastatin. AB - OBJECTIVE: Inactivation of aminoglycosides by beta-lactam antimicrobials both in vitro and in vivo has been documented. Such an interaction has not previously been documented between carbapenems and aminoglycosides. Examination of serum concentrations of tobramycin in a patient receiving both agents suggested that this interaction might exist. The purpose of this study was to look at this question in an in vitro model. METHODS: Low concentrations of tobramycin (10 micrograms/mL) were incubated with imipenem/cilastatin (concentrations of 10, 20, and 40 micrograms/mL) in human serum at 37 degrees C. Aliquots of these solutions were withdrawn at 0, 6, 24, 72, and 120 hours and assayed for tobramycin concentrations using a fluorescence polarization immunoassay. Aliquots of tobramycin 10 micrograms/mL and carbenicillin 200 micrograms/mL were analyzed in the same manner, as a positive control. High concentrations of tobramycin (800 micrograms/mL) and imipenem (5000 micrograms/mL)/cilastatin were incubated together at 21 degrees C and sampled at 0, 6, 24, and 72 hours for tobramycin concentrations. RESULTS: The degradation rates for low-concentration tobramycin and the various concentrations of imipenem/cilastatin were not statistically different from those of the controlled incubations. In contrast, carbenicillin significantly enhanced the degradation rate of tobramycin at this concentration (half-life 72 hours and a 34 percent loss at 24 hours, p = 0.0028). Higher in vitro concentrations of imipenem (5000 micrograms/mL)/cilastatin and tobramycin (800 micrograms/mL) resulted in significant, but moderate degradation over controlled incubations (half-life 80 hours and 10 percent loss at 12 hours, p = 0.0031). CONCLUSIONS: These results suggest that inactivation of tobramycin is not a problem at common clinically achievable imipenem serum concentrations in patients. PMID- 1421668 TI - Chemical compatibility of regional anesthetic drug combinations. AB - OBJECTIVE: To define the physical and chemical compatibilities of several classes of drugs that may be used in combination for peridural anesthesia. DESIGN: Morphine, fentanyl, bupivacaine, lidocaine, tetracaine, ketamine, and clonidine were admixed for one hour in five groups of three-drug combinations, plus one group of all seven drugs. The combinations were inspected macroscopically and microscopically to determine physical compatibility. The admixtures were evaluated by gas chromatography/mass spectroscopy (GC/MS) and compared with known standards to determine chemical compatibility. RESULTS: The admixtures showed no physical incompatibility on microscopic or macroscopic evaluation. Chemical compatibility of all mixtures was confirmed by GC/MS. Ion chromatograms of the drugs in admixtures were identical to previously established standards. CONCLUSIONS: The agents evaluated demonstrated physical and chemical compatibility under conditions that would be observed during the administration of peridural anesthesia. Combinations of these drugs therefore could be safely admixed for use in anesthesia. PMID- 1421669 TI - Hypersensitivity and anaphylactoid reactions to ciprofloxacin. AB - OBJECTIVE: To report three cases of life-threatening hypersensitivity reactions to the oral administration of ciprofloxacin. CASE SUMMARY: Life-threatening hypersensitivity reactions to oral ciprofloxacin, characterized by diffuse, erythematous, nonpruritic, blanching rash, with fever and hypotension, occurred in two HIV-infected patients. One of these reactions was considered anaphylactoid. A similar hypersensitivity reaction was documented in a non-HIV infected patient. DISCUSSION: Premarketing clinical trials described no reports of life-threatening anaphylactoid hypersensitivity reactions to ciprofloxacin. However, postmarketing surveillance studies have documented their occurrence. Seven cases of anaphylactoid reaction to ciprofloxacin have now been documented in HIV-infected patients. CONCLUSIONS: As with trimethoprim/sulfamethoxazole, HIV infected people treated with ciprofloxacin may be at special risk for hypersensitivity reactions. PMID- 1421670 TI - Enhanced anticoagulant effect of coumarin derivatives induced by doxycycline coadministration. AB - OBJECTIVE: To report two cases of enhanced oral anticoagulant effect induced by doxycycline coadministration. DESIGN: Case report. SETTING: University teaching hospital. PATIENTS: Two patients on chronic oral anticoagulation therapy who presented with severe bleeding and marked impairment in blood coagulation tests shortly after the initiation of doxycycline therapy. DISCUSSION: The literature concerning the possible effects of tetracyclines on hemostasis with or without antecedent anticoagulation therapy is reviewed and the speculated mechanisms for such an interaction are discussed. CONCLUSIONS: The administration of tetracyclines such as doxycycline to patients on chronic oral anticoagulation therapy may be associated with a marked enhancement in anticoagulant effect. In such patients the prothrombin ratio should be closely monitored and the anticoagulant dosage adjusted accordingly. PMID- 1421671 TI - Nonthrombocytopenic purpura associated sequentially with nifedipine and diltiazem. AB - OBJECTIVE: To report the case of a patient who developed nonthrombocytopenic purpura sequentially following the administration of nifedipine and diltiazem. DATA SOURCES: Case reports, MEDLINE review of pertinent literature, and review of relevant studies. DATA EXTRACTION: Data were extracted from direct patient observation and review of laboratory studies and published reports. DATA SYNTHESIS: Nonthrombocytopenic purpura secondary to cutaneous vasculitis is a known, although rare, adverse effect of nifedipine. It has not been reported in association with diltiazem. We report the case of a 75-year-old woman in whom a purpuric rash demonstrated by biopsy to be attributable to cutaneous vasculitis developed in the course of nifedipine therapy. The rash disappeared after discontinuation of the drug; however, it recurred when diltiazem therapy was initiated. CONCLUSIONS: Nonthrombocytopenic purpura may be associated with diltiazem as well as with nifedipine. When this adverse effect occurs following administration of a calcium-channel blocker, caution is advised in using other agents of the same class. PMID- 1421672 TI - Case report of a syncopal episode associated with fluoxetine. AB - OBJECTIVE: To report a syncopal episode associated with fluoxetine in a young, relatively healthy man. DESIGN: Single case report. SETTING: 585-bed private hospital. PATIENT: A 30-year-old man with hypertension, esophageal ulcers, and syncope of recent onset. RESULTS: Fluoxetine was started six weeks prior to the syncopal episode in this patient, and is the medication most temporally associated with the event. Because the patient had a normal neurologic examination and electroencephalogram, but an abnormal electrocardiogram on admission and one month after discharge, the syncopal episode was most likely caused by cardiovascular effects of fluoxetine. CONCLUSIONS: Fluoxetine has been reported to cause cardiac conduction abnormalities in otherwise normal individuals. Bradycardia secondary to a direct effect of fluoxetine, or to a drug interaction among fluoxetine, ranitidine, and enalapril is the most likely explanation for this patient's syncopal episode. PMID- 1421673 TI - Profuse diarrhea after misoprostol use in a patient with a history of Crohn's disease. AB - OBJECTIVE: To report a case of profuse diarrhea after misoprostol use in a patient with a history of Crohn's disease and to discuss the role of eicosanoids in Crohn's disease. DATA SOURCES: Patient medical records, case reports, review articles identified by MEDLINE, and personal communication with the physician, patient, and manufacturer. DATA EXTRACTION: From interviews, the manufacturer, and pertinent published sources by one author and reviewed by the others. DATA SYNTHESIS: A 55-year-old woman presented to clinic complaining of multiple joint pains. Her medical history was significant for peptic ulcer disease, hypertension, and Crohn's disease in remission since May 1989. Her joint pains were treated with ibuprofen 600 mg po qid and misoprostol 200 micrograms po qid (after meals and at bedtime). Following the administration of three doses of ibuprofen and misoprostol, the patient experienced abdominal cramps, pain, and voluminous, watery diarrhea for two days. Upon discontinuation of the ibuprofen and misoprostol, all of her gastrointestinal symptoms resolved within 12 hours. Rechallenge with ibuprofen alone failed to produce a recurrence of symptoms. Enhanced synthesis of intestinal eicosanoids has been demonstrated in Crohn's disease. Misoprostol, a synthetic analog of one of the eicosanoids, could induce a flare-up of Crohn's disease as suggested in this patient. CONCLUSIONS: Misoprostol should be used with caution in patients with known inflammatory bowel disease. PMID- 1421674 TI - Oral contraceptive use in osteoporosis. PMID- 1421675 TI - Erythromycin in gastrointestinal motility disturbances. PMID- 1421676 TI - Isoproterenol in the diagnosis of vasodepressor syncope. PMID- 1421677 TI - Clarithromycin: review of a new macrolide antibiotic with improved microbiologic spectrum and favorable pharmacokinetic and adverse effect profiles. AB - OBJECTIVE: To compare the new macrolide antibiotic clarithromycin with erythromycin in terms of in vitro activity, pharmacokinetics, pharmacodynamics, clinical efficacy, and toxicity. DATA IDENTIFICATION: An English-language literature search employing MEDLINE (1987-91), Index Medicus (1987-91), Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy (1990), Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (1991), and bibliographic reviews of related textbooks and review articles. STUDY SELECTION: Eighty-five articles were selected. Clinical trials with clarithromycin have been limited, and emphasis was placed on trials reported in the Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy and Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. DATA EXTRACTION: Articles were assessed for study quality and specific information addressing the stated purpose. In articles reporting the results of clinical trials, emphasis was placed on comparative efficacy and toxicity. RESULTS OF DATA ANALYSIS: A review of 24 human trials suggests that clarithromycin is equally effective as erythromycin, penicillin VK, ampicillin, or amoxicillin for treatment of a variety of upper and lower respiratory tract or skin infections. Clarithromycin also appears to be better tolerated than these agents, with a lower incidence of gastrointestinal adverse effects. Limited clinical studies in patients with Mycobacterium leprae or Mycobacterium avium-intracellulare complex (MAI) suggest that clarithromycin may prove to be efficacious and well tolerated in the treatment of these infections. CONCLUSIONS: Clarithromycin is as effective in vivo as erythromycin, with less gastrointestinal irritation. Additionally, clarithromycin appears to expand the traditional spectrum of macrolide antibiotics, with promising activity against M. leprae and MAI. PMID- 1421678 TI - The triglyceride connection in atherosclerosis. AB - OBJECTIVE: To examine the proposed mechanism of triglyceride-induced atherogenesis, to address the controversy surrounding serum triglycerides as a coronary heart disease (CHD) risk factor, and to recommend an appropriate therapeutic approach to hypertriglyceridemia. DATA SOURCES: Studies, review articles, and editorials published since 1976. A MEDLINE search of English language literature was conducted using the terms triglyceride and hypertriglyceridemia. STUDY SELECTION: Studies, review articles, and editorials were selected for detailed review if they addressed the pathogenesis of triglyceride-induced atherosclerosis, the controversy associated with elevated serum triglyceride as a CHD risk factor, and hypertriglyceridemia treatment options. DATA EXTRACTION: Data were reviewed that described the atherogenicity of chylomicron and very low-density lipoprotein (VLDL) remnants, the inverse relationship that exists between high-density lipoprotein (HDL) and serum triglyceride, the hypertriglyceridemia treatment controversy, and the treatment options of diet, exercise, weight control, alcohol restriction, and medication. DATA SYNTHESIS: Hypertriglyceridemia is a well-known risk factor for pancreatitis. However, its role in atherogenesis is less well defined. Several proposed connections appear to exist between hypertriglyceridemia and atherosclerosis, including the inverse correlation between triglycerides and HDL, the presumed atherogenicity of triglyceride-rich lipoprotein remnant particles, the potential resultant increase in the serum concentration and atherogenicity of low-density lipoprotein (LDL), and the proposed interaction between serum triglyceride and the fibrinolytic/coagulation system. Clinical trials addressing this issue offer mixed results that are subject to interpretation. Diet, exercise, weight control, alcohol restriction, and certain lipid-lowering medications are effective at reducing serum triglyceride. CONCLUSIONS: Hypertriglyceridemia is a theoretical risk factor for CHD because of the increased production of atherogenic chylomicron and VLDL remnants, the inverse relationship present between serum triglyceride and HDL, the possible resultant increase in LDL attributable to remnant-reduced hepatic LDL-receptors as well as the formation of more dense and, therefore, more atherogenic LDL, and to the interaction between serum triglyceride and the fibrinolytic/coagulation system. However, most clinical trials that have found hypertriglyceridemia to be a risk factor for CHD do not include other CHD risk factors in their analyses. Therapeutic intervention to lower serum triglyceride with diet, exercise, and/or drugs is definitely recommended in the treatment and/or prevention of pancreatitis; however, the role of triglyceride-lowering to reduce CHD risk remains controversial. PMID- 1421679 TI - Implications of the study population in the early evaluation of anticholinesterase inhibitors for Alzheimer's disease. AB - OBJECTIVE: Velnacrine testing for tolerance and safety in both normal elderly subjects and patients with Alzheimer's disease (AD) is reviewed to illustrate the importance of Phase I trials in the target group as more predictive of safety and tolerance for subsequent multicenter trials than those conducted in healthy elderly subjects. DESIGN: Both a single-dose and a randomized, double-blind, placebo-controlled, ascending, multiple-dose study were performed with healthy, elderly men. In the multiple-dose study, the subjects were randomized to four groups of 14, with 10 subjects receiving velnacrine and 4 receiving placebo. The doses were velnacrine 25 (group 1), 50 (group 2), and 100 mg (group 3), respectively, administered twice daily; group 4 received 100 mg three times daily for 28 days. Blood and urine were collected serially for the pharmacokinetic assessment. With AD patients, 24 subjects were randomly assigned to receive either placebo or velnacrine for 10 days in a double-blind, sequential escalation study in a hospital setting. There were three groups of 8 subjects. Six patients in each group received velnacrine and 2 placebo. The three groups received respective dosages of 450, 300, and 225 mg/d three times daily. Adverse events were closely monitored and recorded. PATIENTS/PARTICIPANTS: The multiple-dose test in healthy elderly men included 56 men, aged 60-74 years. Rigorous screening for any potential complications that could affect absorption, distribution, metabolism, or excretion preceded patient entry in the AD patient study. Patients with a history of major psychiatric, neurologic, and cardiovascular disorders were excluded. The patients ranged in age from 56 to 89 years, and were equally distributed between gender. INTERVENTION: Velnacrine was administered in various doses. MAIN OUTCOME MEASURES: We emphasize the extreme adverse effects encountered in the AD patient group compared with the healthy group. Plasma concentrations of velnacrine over time in both groups are given, as well as the drug's half-life and excretion rates. RESULTS: The tolerable dosage predicted by studies performed in healthy elderly subjects was 300 mg/d. This dosage was not tolerable among the AD patients. A dosage as high as 450 mg/d resulted in a tonic seizure in one patient. The predicted dosage of 300 mg/d produced an adverse effect profile in AD patients that included dizziness, nausea and/or vomiting, headaches, and severe diarrhea. AD patients tolerated a dosage of 225 mg/d. CONCLUSIONS: A velnacrine dosage of 300 mg/d that was tolerated in healthy elderly subjects was not tolerated by AD patients. PMID- 1421680 TI - Adjuvant corticosteroid therapy for Pneumocystis carinii pneumonia in AIDS patients. AB - OBJECTIVE: To review published abstracts, case reports, and journal articles and evaluate data examining the use of systemic corticosteroids as adjuvant treatment for Pneumocystis carinii pneumonia (PCP) in patients with AIDS. DATA SOURCES: Computerized online databases, peer-reviewed journals from January 1986 through September 1991, and personal communication with a National Institutes of Health correspondent. STUDY SELECTION: The authors identified 13 reports pertinent to this review. By author consensus, five studies were selected for analysis based on sample size, controlled study design, and clinical outcome measures. Recommendations of an expert panel from the National Institutes of Health and the University of California also are discussed. DATA EXTRACTION: Data are presented based on the methodologic strength of the studies reviewed. Studies are assessed on sample size, inclusion criteria, comparative cohort populations, specific patient outcome measures, and statistical analysis. DATA SYNTHESIS: Results of the study analysis support the use of systemic corticosteroids as early adjunctive therapy for AIDS patients with moderate-to-severe PCP who have an initial arterial oxygen partial pressure of less than 70 mm Hg or an alveolar arterial gradient greater than 35 mm Hg on room air. Improved outcomes included decreased mortality, respiratory failure, and deterioration of oxygenation. Data evaluated have shown that adjuvant corticosteroid therapy is most effective when initiated within 72 hours of beginning specific antipneumocystis therapy. A small, but sometimes significant, increased rate of infection in steroid-treated patients was noted. CONCLUSIONS: Based on the literature reviewed, early systemic adjuvant corticosteroid therapy can benefit patients with moderate-to-severe AIDS related PCP. The steroid regimen used in the largest controlled trial and recommended by the expert panel is prednisone 40 mg bid (days 1-5), then 40 mg/d (days 6-10), then 20 mg/d (days 1-21). PMID- 1421681 TI - Serum albumin concentrations: who needs them? AB - OBJECTIVE: To examine the multiple factors that influence serum albumin concentrations and to discuss settings in which the monitoring of such concentrations provides clinically useful information. DATA SOURCES: Original investigations, review articles, books, and abstracts published in English. STUDY SELECTION: Studies pertaining to factors affecting serum albumin concentration were chosen based on general applicability. Recommendations related to the appropriate monitoring of albumin concentrations were based on studies performed in the clinical setting with direct applicability to patient care. DATA EXTRACTION: Data on factors affecting serum albumin concentration were extracted from studies that resulted in similar conclusions regardless of assay technique. Appropriate indications for albumin monitoring were derived from studies demonstrating direct clinical relevance. DATA SYNTHESIS: A number of factors may influence serum albumin concentration and ultimately affect interpretation of the concentration. Serum albumin concentrations generally are useful in the institutional setting shortly after admission or preoperatively to determine patient prognosis. Albumin concentrations have limited merit for predicting the free fractions of various hormones, electrolytes, and drugs. When used as an indicator of nutritional support, albumin concentrations are most helpful when measured over longer periods in relatively stable patients. CONCLUSIONS: Serum albumin determinations should be limited to those situations in which the concentrations are likely to provide clinically useful information. Such situations are limited. PMID- 1421682 TI - Home total parenteral nutrition in a "no-bowel" patient in Spain. AB - OBJECTIVE: To report a case of a patient with no functional bowel who was receiving home total parenteral nutrition in a country that has had a few professional experiences in this area of therapy. CASE SUMMARY: A woman with a history of scattered colonic polyposis developed a mesenteric tumor that caused intestinal obstruction. Tumor withdrawal required the excision of 1.5 m of jejunum-ileum. Postoperative complications required further surgical intervention and subtotal intestinal resection. Duodenocolic anastomosis was not possible and a high output and permanent fistula remained. DISCUSSION: The complications of home parenteral nutrition addressed in the literature are reviewed. The problems encountered in our patient have been resolved. CONCLUSIONS: After three years of postoperative survival, we believe the quality of life of our patient has increased and the parenteral nutrition team members are much better prepared to manage patients with similar problems. PMID- 1421683 TI - Sulfur compounds in therapy: radiation-protective agents, amphetamines, and mucopolysaccharide sulfation. AB - OBJECTIVE: Sulfur-containing compounds have been used in the search for whole body radiation-protective compounds, in the design of amphetamine derivatives that retain appetite-suppressive effects but lack most behavioral effects characteristic of amphetamines, and in the search for the cause of kidney stone formation in recurrently stoneforming patients. METHODS: Organic synthetic procedures were used to prepare radiation-protective compounds having a variety of sulfur-containing functional groups, and to prepare amphetamine derivatives having electron-attracting sulfur functions. In the case of the kidney stone causation research, isolation of urinary mucopolysaccharides (MPS) from recurrently stoneforming patients was carried out and the extent of sulfation of the MPS was determined by electrophoresis. RESULTS: Whole-body radiation protective agents with a high degree of protection against lethal doses of gamma radiation in mice were found in a series of quinolinium and pyridinium bis(methylthio) and methylthio amino derivatives. Mechanism studies showed that the copper complexes of these agents mimicked the beneficial action of superoxide dismutase. Electron-attracting sulfur-containing functions on amphetamine nitrogen, as well as 4'-amino nitrogen provided amphetamine derivatives with good appetite-suppressant effects and few or no adverse behavioral effects. Higher than normal levels of sulfation of the urinary MPS of stone formers suggested a cause for recurrent kidney stone formation. A sulfation inhibitor was found to prevent recurrence of stone formation and inhibit growth of existing stones. CONCLUSIONS: The inclusion of various sulfur-containing functions in organic molecules yielded compounds having whole-body radiation protection from lethal doses of gamma-radiation in animals. The presence of electron-attracting sulfur functions in amphetamine gave derivatives that retained appetite-suppressant effects and eliminated most adverse behavioral effects. A therapy for recurrent urolithiasis resulted from inhibition of MPS sulfation, after the finding that stoneforming patients had abnormally high levels of MPS sulfation. PMID- 1421684 TI - Appropriateness of mandatory patient counseling. PMID- 1421685 TI - Critical analysis of the content and enforcement of mandatory consultation and patient profile laws. AB - OBJECTIVE: This study evaluates the experience of 12 states that mandate that pharmacists provide consult services to patients and maintain drug profiles. DATA SOURCES: An analysis of each state's statutes and regulations was complemented by telephone interviews of state licensing board staff. RESULTS: Nine states specify the information to be provided during consultations, but only one (Florida) requires a comprehensive list of drug information, including adverse drug reactions, drug-drug interactions, directions for use, and necessary warnings. Eleven of the 12 states also require pharmacists to maintain patient drug profiles, but only 6 states specify the type of information to be included in profiles. State efforts to inform consumers about the pharmacist consultation requirement are limited, with only 7 states undertaking minimal promotional programs. The fact that no states reported any consumer consultation complaints or disciplinary actions against pharmacists for failure to consult illustrates the limited nature of mandatory consultation statues and regulations. CONCLUSIONS: The wide variety of requirements demonstrates that these laws do not represent a uniform standard of practice. The lack of documented evidence regarding implementation invites questions regarding their usefulness and reinforces the need for enhanced monitoring activities. PMID- 1421686 TI - Unresponsiveness to human recombinant erythropoietin in an epileptic dialysis patient secondary to valproic acid toxicity. PMID- 1421687 TI - Treatment of viral hemorrhagic fevers with ribavirin. PMID- 1421688 TI - Comment: cecal vitamin bezoar formation inducing abdominal discomfort. PMID- 1421689 TI - Comment: ketorolac formulary restriction and usage evaluation. PMID- 1421690 TI - [Molecular bases of tumor cell invasiveness]. PMID- 1421691 TI - [Review of results and clinical analysis of conservative partial surgery associated with postoperative radiotherapy in operable breast cancers stages I amd II]. AB - Over the last 25 years, conservative forms of treatment have been used for the locoregional treatment of early breast cancer, stages I and II (< 3 cm in diameter). At present, the same carcinological results are obtained with conservative surgery and radiation therapy as with radical surgery, and the aesthetic and functional results have improved. Several parameters should be taken into account, ie tumour volume, breast volume, multifocal nature and histologic type. A number of questions still remain unanswered namely: what is the most appropriate conservative surgery (quadrantectomy, tumourectomy or local excision)? What is the most appropriate total irradiation dose (50 Gy over 5 weeks: or 45 Gy over 4.5 weeks)? What is the value of radiation boost in patients with negative resection margins? What is the value of radiation boost in patients with a high local risk of recurrence? What is the most appropriate radiation technique for boost in the primary tumour bed (electrons or iridium implants)? Does the external irradiation of regional lymph nodes improve survival rate? Is it possible to extend conservative treatment to a 4-cm diameter tumour? What is the impact of adjuvant systemic chemotherapy and/or hormonotherapy on the risk of isolated breast cancer recurrence? PMID- 1421692 TI - E-cadherin expression: a counterbalance for cancer cell invasion. AB - Invasion, eventually leading to metastasis, is presented as the result of a balance between the activation of 2 sets of genes, coined i+ (invasion promotor) and i- (invasion suppressor) genes. Experiments in vitro have indicated that the homotypic homophilic epithelial cell--cell adhesion molecule E-cadherin (L-CAM; uvomorulin; cell CAM 120/80; Arc-1; rrl antigen) is an i- gene product. In several cell families, manipulation of E-cadherin at the level of the protein by antibody-mediated inactivation, at the level of the mRNA by antisense DNA transfection, and at the level of the genome by sense DNA transfection respectively resulted in induction and suppression of invasiveness. Nude mouse tumors from non-invasive homogeneously E-cadherin-positive cell populations were found to be invasive and metastatic. These tumors expressed E-cadherin in a heterogeneous manner, the undifferentiated cells being negative; but tumor derived cells in culture were again E-cadherin-positive, indicating downregulation of this protein by host factors. Several types of human cancers showed a similar heterogeneity suggesting a relationship between downregulation of E-cadherin and invasion. Our current research focus is on the factors responsible for E-cadherin downregulation in experimental and human cancers. PMID- 1421693 TI - [Regulation by protein kinase C of TGF-beta 1 expression in cultured cells of breast adenocarcinoma]. AB - In human breast carcinoma MCF-7 cells, phorbol diesters inhibit proliferation and induce cell maturation. We investigated the involvement of TGF-beta 1 in the PCK mediated inhibition of breast cancer cell proliferation. Using an RNase protection assay, we showed that TPA induced a dose-dependent increase in levels of TGF-beta 1 mRNA that paralleled the inhibitory effect on MCF-7 proliferation. Similar results were obtained with another TPA-sensitive breast cancer cell line (BT-20). TPA did not increase TGF-beta 1 mRNA levels in the MCF-7:RPh-4 and T47D cell lines, which are both insensitive to the growth inhibitory effects of phorbol esters. In addition, the increase in TGF-beta 1 mRNA level was not observed after treatment of the MCF-7 cell with other inducers of cell differentiation such as forskolin, DMF, HMBA and sodium butyrate. The induction of TGF-beta 1 mRNA by TPA along with its inhibitory effect on cell proliferation suggests that TGF-beta 1 mediates, at least in part, the inhibitory effect of PKC activation. PMID- 1421694 TI - [5-FU cardiotoxicity in adjuvant chemotherapy for colonic cancer letter)]. PMID- 1421695 TI - [What can be learned from cancers occurring after therapeutic radiation? Proceedings of a meeting of the French Society of Radioprotection. Paris, 27 March 1992]. PMID- 1421696 TI - [What can be learned from cancers occurring after therapeutic radiation? Introduction]. PMID- 1421697 TI - [Radiation-induced skin cancers and leukemia. Historical data]. PMID- 1421698 TI - [Thyroid tumors after radiotherapy]. PMID- 1421699 TI - [Cancers after radiotherapy in children]. PMID- 1421700 TI - [Secondary neoplasms after allograft of bone marrow. Role of irradiation]. PMID- 1421701 TI - [Secondary solid tumors after Hodgkin's disease radiotherapy; experience at the Gustave Roussy Institute]. PMID- 1421702 TI - [Second cancers after treatment of Hodgkin's disease: experience at the International Database on Hodgkin's disease (IDHD)]. PMID- 1421703 TI - [Second tumor after bone marrow graft. Analysis of 265 total body irradiation in children from January 1980 to December 1990 at the Leon-Berard Center]. PMID- 1421704 TI - [Genetic predispositions of second cancers]. PMID- 1421705 TI - [Apoptosis or programmed cell death: concepts, mechanisms and contribution in oncology]. AB - Programmed cell death, or apoptosis, corresponds to a sequence of intracellular events that lead to cell death. It has been shown that apoptosis is necessary in some physiological conditions such as embryogenesis, homeostasis of the immune system, erythropoiesis, etc. Some xenobiotics can induce apoptosis at lower doses and necrosis at higher doses. When a cell dies, it is either by apoptosis or by necrosis, and there are many differences between these two deaths. Apoptosis begins by a pre-commitment phase, which is reversible; during this phase the cell has a high level of second messengers. The commitment phase then follows and is irreversible, even when the xenobiotic that triggered the induction is removed. Most often, apoptotic cell death requires synthesis of macromolecules, the inhibition of their synthesis can prevent it. The cell undergoes important morphological changes during apoptosis, its volume decreases when its density increases. Then chromatin becomes granular, intensively osmiophilic, it condenses along the nuclear membrane. Later, chromatin disintegrates into small granules which will be phagocytized. One of the most important characteristics of the programmed cell death is the activation of an endonuclease, that gives rise to DNA fragments of 180-200 base pairs or multiples of these numbers; then after electrophoresis, the DNA gives the appearance of a ladder. Apoptotic cells can be characterized after classic staining, and flow cytometry; they can be separated from other cells by centrifugation on a gradient of density. It has been hypothesized that cell transformation could be due to a sudden resistance to apoptosis. However, the most interesting aspect in oncology recently demonstrated is that well-known anticancer drugs are able to induce apoptosis. One can hope that the discovery of new targets for anticancer drugs could lead to discovering new drugs that could be more active. PMID- 1421706 TI - [Growth factors and intestinal cancers]. AB - This review focuses on the growth factors (primarily IGFs, TGF-alpha and TGB beta) that control both proliferation and differentiation of the normal intestinal epithelial cells and their involvement in intestinal tumorigenesis. Integrity of the digestive tissue is dependent on continuous coordination between cell growth and maturation along the crypt- villus axis. Beyond an intricate network of various regulatory molecules, such a regulation is essentially in close connection with the opposite biological effects delivered on a same target cell by TGF-alpha and TGF-beta. Growth factors act via regulatory autocrine/paracrine loops that are physiological means to deliver biological signals throughout the normal gut tissue. During tumorigenesis, cell progressively lose their sensitivity towards such extracellular regulatory loops. TGF-alpha insensitivity is linked to constitutive activation of intracellular pathways that induce uncontrolled cell growth. The incapacity to respond to TGF beta that is due to an alteration of its intracellular pathway does not allow the negative regulation of cell proliferation or the induction of cell differentiation. Concurrently, the disappearance of an IGF-II extracellular autocrine loop appears to be correlated with cells maintained in an undifferentiated state. These alterations lead to a break between the metabolic pathways involved in the delicate control of the proliferation/differentiation balance. This leads to an unscheduled increase of positive proliferative signals which are responsible for an uncoordinated epithelial cell growth that favour tumor cell clone outgrowth. From these experimental data, essentially obtained in vitro, we propose a tentative colorectal tumorigenesis model that links both growth factor pathways and genetic (oncogenes and tumor suppressor genes) alterations. However, such a model only represents a part of the multiple cell and molecular interactions that are set in action in vivo. It remains to decipher their consistency in order to improve new therapeutic strategies. PMID- 1421707 TI - [Mammary microcalcifications: is there a consensus on interpretation and management?]. AB - Twenty two view mammograms without magnification, with microcalcifications corresponding to non palpable breast lesions, were submitted to 23 experienced observers, either gynaecologists or radiologists. These mammograms consisted of 10 malignant lesions and 10 benign lesions; all of them underwent surgical procedures. The microcalcifications were graded and categorized into one of the four groups: malignant; suspect; slightly suspect; benign. One of the four options was proposed: biopsy; mammogram within 3 months; mammogram within 6 months; mammogram within a year. Twelve observers out of 23 have referred to a classification. The mammograms were assessed according to a consensus. The validity of that diagnostic test was studied in various clinical situations and the lack of homogeneity of the responses was quantified. In the trade-off situation between sensitivity and specificity (suspect or malignant considered as positive), sensitivity is 50% and specificity is 70%. Moreover, the responses are not homogeneous at all and this lack of homogeneity is found to be statistically significant, greater than by chance alone. The diagnosis of cancer is more frequently put forward by the radiologists. This study explains the low predictive value of non palpable microcalcifications undergoing surgical procedures: from 11.5 to 44% in the literature. Similarly, there is no agreement on the frequency of the follow-up for these microcalcifications when they do not lead to surgical procedures. PMID- 1421708 TI - [Meta-analysis of adjuvant medical treatment in breast cancers. Ten year results]. AB - The ten-year results of the meta-analysis of the adjuvant systemic treatment of early breast cancer are summarized. The five-year results are confirmed and a few new informations arise: tamoxifen is more efficient when given more than two years; the results of chemotherapy are significant in post-menopausal patients less than 70 years old. PMID- 1421709 TI - [Puncture of bone lesions under tomodensitometric control]. AB - Sixty CT-guided fine needle biopsies were performed on 59 patients. Of the 40 lesions in patients with a previous history of cancer, malignancy was confirmed by cytological examination in 27 cases and benignity in three cases. Of the 20 lesions in patients with no previous history of cancer, malignancy was confirmed in nine cases (45%) and benignity in five cases (25%). This precise and safe procedure shows 78% overall accuracy in this series. PMID- 1421710 TI - A phase II trial of early intensive chemotherapy with autologous bone marrow transplantation in the treatment of poor prognosis non seminomatous germ cell tumors. AB - Twenty-eight patients with poor prognosis, advanced metastatic non seminomatous germ cell tumors (NSGCT) were treated with early high dose chemotherapy and autologous bone marrow transplantation (ABMT) rescue. The primary tumor was testicular in 19 patients and extragonadal in nine patients. For 19 patients with a testicular primary, the median probability of complete remission (CR) was 0.05 according to our prognostic mathematical model based on pretreatment levels of serum HCG and AFP. The same prognostic model was used for extragonadal primaries. Treatment consisted of two cycles of a modified double dose of cisplatin, vinblastine, bleomycin, VP-16 regimen (mPVeBV) followed by a high dose cisplatin etoposide-cyclophosphamide regimen (PEC) followed by ABMT. Of the 28 patients, 17 (61%) achieved CR, one of which was surgical CR (sCR), five died of rapidly progressive disease early during the first cycle of mPVeBV, two had treatment related deaths, three did not respond and one patient refused treatment. Of the 17 patients initially in CR, three relapsed after 4, 4 and 7 months respectively and have subsequently died. Two other patients died while still in CR: one committed suicide and one died of an infectious complication due to transfusion related AIDS. Twelve patients are alive in CR after a median follow-up of 66 months (range 7-72 months). The non parametric 3-year survival rate is 40%. To demonstrate the effect of intensive chemotherapy with ABMT, a randomized multicenter French study was set up to evaluate the PVeBV regimen with or without high dose treatment and ABMT in poor risk NSGCT patients. PMID- 1421711 TI - Histocompatibility antigens associated with Behcet's disease in northern Han Chinese. AB - Among Han nationality Chinese and living in the northern area of the Yellow River, 120 patients suffering from Behcet's disease and 100 unrelated healthy individuals were typed for histocompatibility antigens (HLA)-A, -B, -C, and -DR and -DQ antigens. HLA-DR and DQ typing was performed on B-lymphocyte separated with Lympho-B-Kwik. The HLA-antisera were provided by 11th IHWC. Bf alleles and C4 allotypes were determined by immunofixation agarose-gel electrophoresis. HLA B51 was found in 67/120 (55.83%) patients and in 12/100 (12%) controls, the Chi square and relative risk values were 45.54 and 9.27, respectively (p < 0.0005). C4AQ0 frequency was significantly increased in the patient group. In the complete form group HLA-B51 was observed more frequently (62.79%). No significant differences of other HLA antigens, frequencies, Bf or B4 alleles were found between the groups. PMID- 1421712 TI - Type 1 (insulin-dependent) diabetes mellitus with coexisting autoimmune thyroid disease in Japan. AB - Type 1 diabetes mellitus is known to be a heterogenous disease which is frequently complicated with other autoimmune thyroid diseases (AITD). The present study was designed to investigate the clinical characteristics and HLA antigens in Japanese Type 1 diabetic patients with AITD. Subjects were 25 Type 1 diabetic patients with AITD (13 Graves' disease and 12 Hashimoto's thyroiditis) and 32 Type 1 diabetic patients without AITD. Compared with Type 1 diabetic patients without AITD, age at onset of diabetes was later and positive ICA persisted much longer in the diabetic patients with AITD. Compared with normal controls, DR9 was increased in the patients with AITD, while DR4 was increased in those without AITD. Type 1 diabetic patients with AITD were characterized by the late onset of diabetes, persistent ICA and increased association with DR9. These results suggest that immunological and genetic heterogeneity may exist within Japanese Type 1 diabetic patients. PMID- 1421713 TI - Central motor conductivity in aged people. AB - The conductivity of motor neurons in 26 aged females (mean age 79 years) was analyzed by the conventional conduction method and by pulsed magnetic stimulation and compared with that in 14 younger controls. In aged people, slow motor conduction velocities were found in peripheral nerves. Central motor conduction time (CMCT) in relaxed muscle was shorter in the aged people, although CMCT was normal in mildly contracted muscle. These findings coincide with the results studied in Parkinson's disease, although these subjects were not diagnosed as having Parkinson's disease. Aged people generally have an anteflexed posture, slow movements, and poor postural reflexes, and have been reported to have a decrease in the dopamine level which is relatively earlier than that of other transmitters in the basal ganglia. This may account for the present finding that aged people have neurophysiological abnormalities in CNS which are similar to those in Parkinson's disease. PMID- 1421714 TI - Unoperated thoracic aortic aneurysms: survival rates of the patients and determinants of prognosis. AB - The purpose of this study was to evaluate the long-term prognosis of unoperated thoracic aortic aneurysms, and to detect the risk factors which determine the prognosis of unoperated patients. The subjects were 52 unoperated patients with 58 thoracic aortic aneurysms (22 of the ascending aorta, 36 of the descending aorta or the aortic arch) and 38 with abdominal aortic aneurysms. The survival rates of the patients with ascending aortic aneurysms at 3 years and 5 years and those of the patients with descending aortic aneurysms at 5 years were significantly higher than those of the patients with abdominal aortic aneurysms. The risk factors for rupture of thoracic aortic aneurysms were the large size of aneurysms and non-management by the cardiologist and the risk factors for death unrelated to the aneurysms were patient age, male gender and non-management by the cardiologist. PMID- 1421715 TI - Phonoechocardiographic identification of chordal snap in hypertrophic cardiomyopathy. AB - In three patients with hypertrophic cardiomyopathy, a late systolic click following mid systolic murmur was recognized. M-mode and two-dimensional echocardiography showed the presence of systolic anterior motion of the chordae tendineae in all cases. Phonoechocardiographic studies showed that the time of the click always coincided with the endpoint of mild anterior motion of the chordae tendineae. The click was considered to be a chordal snap. PMID- 1421716 TI - Endobronchial involvement with Waldenstrom's macroglobulinemia. AB - Although many cases of Waldenstrom's macroglobulinemia (WMG) with pulmonary involvement have been reported, endobronchial involvement has not been described. We report an unusual case of WMG wherein endobronchial invasion of tumor cells narrowed the airways and caused coughing and wheezing. PMID- 1421718 TI - Anaplastic thyroid carcinoma with prominent cardiac metastasis, accompanied by a marked leukocytosis with a neutrophilia and high GM-CSF level in serum. AB - Cardiac metastasis of thyroid carcinoma is extremely rare. We treated a case of anaplastic thyroid carcinoma with prominent cardiac metastasis. The 61-year-old male was admitted because of high fever. Investigations revealed a cardiac mass and anaplastic thyroid carcinoma. Resection of the cardiac mass revealed that it was metastasis from the thyroid carcinoma. After 4 months, he died in spite of intensive therapy. Marked leukocytosis was observed during the clinical course, and a concomitant increase of granulocyte macrophage-colony stimulating factor (GM-CSF) level was demonstrated in the sera. It was suggested that the high GM CSF level in serum contributed to leukocytosis. PMID- 1421717 TI - Pentasomy X mosaic in two adult sisters with diabetes mellitus. AB - Pentasomy X mosaic in two adult sisters with non-insulin dependent diabetes mellitus is described. The younger sister had schizophrenia, and both were mentally retarded, but no apparent somatic abnormalities were found. Chromosome analyses revealed karyotype 45,X/46,XX/47,XXX/48,XXXX/49,XXXXX mosaic with a low frequency of aneuploidy on cultured peripheral lymphocytes and 46,XX on cultured skin fibroblasts in both sisters. The low frequency of X chromosome aberration may be responsible for the lack of somatic abnormalities and the long life in both sisters. The association of pentasomy X mosaicism and diabetes mellitus however appears to be coincidental. PMID- 1421719 TI - Partial anomalous pulmonary venous return showing anomalous venous return to the azygos vein. AB - Partial anomalous pulmonary venous return (PAPVR) is a congenital heart disease with a reported incidence of autopsied case. The location of the anomalous pulmonary venous return is usually the right atrium, superior vena cava (SVC), and sometimes the brachiocephalic vein, inferior vena cava (IVC) or coronary venous sinus. Recently we experienced a rare case of PAPVR showing anomalous right total pulmonary venous return to the azygos vein. Furthermore, downward translocation of the right upper lobe bronchus was evident. This rare case is reported along with a review of the related literature. PMID- 1421720 TI - Thyroid papillary adenocarcinoma in a woman with Peutz-Jeghers syndrome. AB - We present a rare case of Peutz-Jeghers(P-J) syndrome in a 29-year-old woman who developed adenocarcinoma of the thyroid and polyps in the gastrointestinal tract. Polyps removed from the stomach, colon and ileum showed features typical of hamartomas. Histological examination indicated that the tumor resected from the right lobe of the thyroid was a papillary adenocarcinoma. This appears to be the first precise report of a P-J syndrome associated with thyroid carcinoma. This case adds an example of predisposition of P-J syndrome to extra-intestinal malignancy and indicates the importance of long-term observation of malignancy. PMID- 1421721 TI - Bartter's syndrome with gouty arthritis. AB - A 45-year-old woman with Bartter's syndrome complicated with gouty arthritis is reported. Bartter's syndrome was diagnosed from hypokalemia, metabolic alkalosis, high plasma renin activity, normal blood pressure and attenuated pressor response to exogenous angiotensin II infusion. Serum uric acid was 11.8 mg/dl, the renal clearance of uric acid was low (3.0 ml/min) and fractional excretion of uric acid (FEUA) was 7.0%, being the lower limit of the normal range. Fractional excretion of phosphate was low (5.3%) and fractional free water clearance per fractional distal sodium delivery was 0.51. The mechanism of hyperuricemia in this case is discussed. PMID- 1421722 TI - Multiple liver abscesses secondary to Yersinia enterocolitica. AB - A 37-year-old male, a poorly-controlled insulin-dependent diabetic patient, was admitted to our hospital with complaints of high fever and confusion. Laboratory data showed hyperglycemia, positive inflammatory reaction and liver dysfunction. Blood culture demonstrated Yersinia enterocolitica. Liver CT scan showed multiple low density areas. These data were consistent with a diagnosis of liver abscess secondary to Yersinia enterocolitica. He died of disseminated intravascular coagulation; subsequent autopsy confirmed the clinical diagnosis. Liver abscess secondary to Yersinia enterocolitica with septicemia is rare, but has been reported in compromised hosts. In the mechanism of this disease, the alimentary tract has been suggested to be the port of entry in most cases. PMID- 1421723 TI - Wegener's granulomatosis in a patient with a rheumatoid arthritis. AB - A 38-year-old woman with rheumatoid arthritis who developed Wegener's granulomatosis is described. Wegener's granulomatosis appeared with saddle nose, perforation in her nasal septum, and granuloma in the nasal cavity. Laboratory evaluation showed a positive rheumatoid factor and circulating immune complex. Radiographic examination revealed ankylotic changes in both wrist and elbow joints. Bilateral anosmia and other disease manifestations completely responded to treatment with oral cyclophosphamide and prednisolone. PMID- 1421724 TI - Immunological studies on opportunistic infection and the development of adult T cell leukemia. AB - Three patients with opportunistic infection preceding adult T-cell leukemia (ATL) are presented: a 66-year-old woman with cryptococcosis and Pneumocystis carinii pneumonia, a 46-year-old man with Pneumocystis carinii pneumonia, and a 55-year old woman with cryptococcosis. Although, at the first examination, the first two had smoldering type ATL and the third case was an HTLV-I carrier, all three developed overt ATL 14-16 months after the onset of opportunistic infection. It is considered that there is immune suppression already present in HTLV-I carriers and in patients with smoldering ATL, and opportunistic infection is predictive of the development of ATL. PMID- 1421725 TI - Post-splenectomy meningitis in patients with lymphoid malignancy. AB - This report describes pneumococcal meningitis in two splenectomized patients with lymphoid malignancy. Early diagnosis and emergency treatment of pneumococcal infection in splenectomized patients is proven to be of significant value. Prophylactic antibiotics targeted against pneumococcus should be considered for the clinical management of such conditions in splenectomized patients, particularly during cytotoxic chemotherapy. PMID- 1421726 TI - Idiopathic acute eosinophilic pneumonia. AB - A previously healthy young man presented with acute respiratory distress, high fever and bilateral ground-glass appearance on chest radiograph. Bronchoalveolar lavage analysis demonstrated significant eosinophilia (72%) with no evidence of infection. The transbronchial lung biopsy showed that the walls of bronchioli and alveolar septa were markedly infiltrated with eosinophils. The patient rapidly improved with corticosteroid therapy. This case exemplifies the recently described idiopathic acute eosinophilic pneumonia. Similar cases published in the Japanese literature were reviewed and discussed. PMID- 1421727 TI - Persistent hemichorea associated with thyrotoxicosis. AB - We describe a case with unilateral chorea associated with thyrotoxicosis. A 23 year-old female with no family history of neurological diseases acutely developed choreic movements of the left extremities during gross thyrotoxicosis. CT scan and MRI study demonstrated no abnormality. Single-photon emission CT with technetium Tc 99m-labeled hexamethylpropyleneamine oxime revealed normal cerebral perfusion. Although the choreic movements were partially improved by dopamine antagonist, they persisted for two months until successful treatment of the thyrotoxicosis finally abolished these movements. Increased sensitivity of dopamine receptors may be responsible for persistent choreic movements in thyrotoxicosis. PMID- 1421728 TI - Granulomatous hypophysitis with meningitis and hypopituitarism. AB - We report an unusual case of granulomatous hypophysitis in which visual impairment, meningitis and hypopituitarism in a 76-year-old female were associated with radiological evidence of a pituitary mass. The sellar lesion was indistinguishable from pituitary tumor on neuroimaging studies, but the recovery of visual acuity and visual field abnormalities together with the improvement of pituitary function after steroid administration indicated that the mass lesion was due to an inflammatory disease of the pituitary gland. The pituitary tissue obtained by transsphenoidal hypophysectomy revealed granulomatous inflammatory cell infiltration with epithelioid cells and scattered multinucleated giant cells. Although a causal relationship with meningitis was not ascertained, possible exposure of the CSF space to the autoimmune inflammatory process of the pituitary gland was likely in view of the positive pituitary antibody reaction and radiological evidence of suprasellar extension. This entity should be considered when evaluating patients with a pituitary mass, hypopituitarism and meningitis. PMID- 1421729 TI - Thoracic extramedullary hematopoiesis associated with hereditary spherocytosis. AB - A 54-year-old man was diagnosed with hereditary spherocytosis. An X-ray of the chest disclosed bilateral round masses in the upper and lower posterior mediastinum. CT showed homogeneous round masses of soft tissue density in the posterior mediastinum. A needle biopsy of the mass showed hyperplastic erythroid bone marrow. Fatty metamorphosis of the masses was observed in CT 2 years after splenectomy but showed no change in size. PMID- 1421730 TI - Bronchopulmonary disease in ulcerative colitis. AB - Two cases of ulcerative colitis are described: a 33-year-old woman who developed widespread bronchiectasis 7 months after undergoing colectomy, and a 72-year-old man whose colonic disease began coincidentally with the appearance of diffuse interstitial pulmonary infiltrates. In both cases, clinical correlation and common patterns of response of lung and bowel diseases suggested that the co existence of these two pathologies might not be merely a casual relation. PMID- 1421731 TI - Clinical practice guideline: acute pain management. PMID- 1421732 TI - Detoxification of nonopiate drugs in the chronic pain setting and clonidine opiate detoxification. AB - Although the pain physician is most familiar with the treatment of the opiate withdrawal syndrome, other drugs are abused by the chronic pain patient. The pain physician should then be familiar with the withdrawal syndromes associated with other drug groups. The withdrawal syndromes associated with hypnosedatives, psychotomimetics, nicotine, stimulants, ergot alkaloids, beta adrenergic blocking agents, antidepressants, muscle relaxants, and alpha-adrenergic agonists are described. Drug detoxification protocols for these drugs are reviewed. Additionally, the rationale for clonidine opiate detoxification is discussed, and current clonidine detoxification protocols are reviewed. PMID- 1421733 TI - Chronic-pain medications: equivalence levels and method of quantifying usage. AB - Medication use is an important consideration in chronic-pain rehabilitation programs (CPRPs). However, it is difficult to quantify this aspect of chronic pain treatment, because patients often take multiple medications that can differ by pharmacological class as well as dosage level. The Medication Quantification Scale (MQS) provides a method for quantifying medication use in patients with chronic, nonmalignant pain. Scores are calculated for each medication based on weights assigned by medication class and dosage level, and these scores are summed to provide a quantitative index of total medication usage suitable for statistical analysis. The method for calculating MQS scores is illustrated, and research data on MQS reliability and validity are presented. Interrater reliability was rho = 0.985 (p less than 0.0001) for 30 MQS scores calculated by two clinicians. MQS scores for 88 patients correlated well with the clinical judgment of 12 health care professionals (mean rho = 0.755, p less than 0.0001). The MQS scores for 60 chronic-pain patients (30 treated in a CPRP and 30 untreated) were obtained at two time points: evaluation and 1-year follow-up. A two (groups) by two (time points) analysis of variance yielded a significant group-by-time interaction (F = 8.82, p less than 0.0043). Treated patients decreased their medication intake significantly (p less than 0.0001), whereas untreated patients did not (p greater than 0.57). The MQS offers a reliable and valid method for quantifying medication usage in chronic-pain patients. PMID- 1421734 TI - Patient controlled analgesia: the relation of psychological factors to pain and analgesic use in adolescents with postoperative pain. AB - OBJECTIVE: To examine the relationship of psychological variables to pain and patient-controlled analgesia (PCA) use in adolescents undergoing orthopedic surgeries. DESIGN: Cohort. PATIENTS: Fifty adolescents and their parents. MAIN OUTCOME MEASURES: Visual analogue scales of pain, the McGill Pain Questionnaire, and questionnaires that assessed overall psychological distress, anxiety, and family environment. RESULTS: Correlations of the psychological variables with measures of pain and PCA use showed that high levels of anxiety and distress in adolescents were related to higher postoperative pain. Adolescents from controlling and conflicted families also had higher pain ratings and made more frequent PCA demands during the lockout interval when drug was unavailable. Parent anxiety and distress were also related to adolescent pain and PCA use. CONCLUSIONS: The psychological status of adolescents and their parents can significantly influence postoperative pain and PCA use. PMID- 1421735 TI - MMPI scale 3 as a predictor of back injury report: what does it tell us? AB - Items and selected subscales of Scale 3 (Hysteria) of the MMPI were examined to pinpoint personality or emotional factors predictive of back injury reports in an industrial setting. Data were derived from a previous prospective-design study of back pain in volunteer hourly wage employees of an aircraft manufacturing company. After physical examination and completion of questionnaires pertaining to demographic, psychosocial (including the MMPI), and workplace factors, workers were followed for an average of 3 years. Those who subsequently reported back injury were compared with those who did not. In that study three variables predicted report of back injury, one of which was Scale 3 of the MMPI. Individual items, Ornduff et al. subscales of Psychological Denial and Body Concern, and the five Harris-Lingoes (1955) subscales of Scale 3 were analyzed. Three Harris Lingoes subscales showed significant relationships to the criterion. Hy-3: Lassitude/Malaise; Hy-1: Denial of Social Anxiety; and, marginally, Hy-2: Need for Affection, significantly contributed to prediction effectiveness. Results and implications for the understanding of factors predicting back injury reports and for the medical evaluation of pain and the concept of pain are discussed. PMID- 1421736 TI - An 18-month follow-up of a secondary prevention program for back pain: help and hindrance factors related to outcome maintenance. AB - Thirty-six subjects participated in an 18-month follow-up of a secondary prevention program for back pain of recent onset. The follow-up assessment included most of the same instruments used in the original study. In addition, interviews were conducted to ascertain help and hindrance factors for maintaining improvements during the follow-up period. Results showed that subjects had significantly less pain, used fewer medications, and were more active at 18-month follow-up than at baseline. All subjects had returned to work, and one third had no pain-related work absences during the follow-up. A cost-benefit analysis indicated substantial economic savings when follow-up sick-listing data were compared with estimates based on an increasing trend for pain-related absenteeism found during the baseline period. Hindrance factors reported by subjects were related to personal time-management and workplace factors, especially psychosocial aspects of the work environment. It was concluded that the secondary prevention program was effective and that future maintenance programs should focus more on personal time-management and workplace factors. PMID- 1421737 TI - Persistent low-back pain is real. However, diagnostic spinal injections are not helpful in its evaluation. AB - We endeavored to assess the short-term effects of intrathecal fentanyl and lidocaine in chronic-pain patients by ascertaining whether the opioid fentanyl, by virtue of its lack of sensory and motor paralysis, conferred any diagnostic advantages over lidocaine, a local anesthetic whose effects include sensory and motor paralysis. Neuraxial administration of fentanyl has been touted as an improved diagnostic tool to distinguish between peripheral and central pain, because the absence of sensory and motor effects may avert the patient's presumption of the onset of analgesia based on these cues. Twenty-two patients with persistent low-back pain, whose investigations had determined that they were not surgical candidates, were studied using a counter-balanced, placebo controlled, and double-blinded crossover design. Each patient received three separate lumbar intrathecal injections of equal volume (1.4 ml): cerebrospinal fluid, fentanyl 25 micrograms, and lidocaine 70 mg. Pain and symptom assessments were performed preinjection (baseline), and at regular intervals up to and including 4 h postinjection. Pain was evaluated by verbal patient response using a numerical pain-rating system of 0 to 10. Duration of analgesia, sensation of warmth, and adverse effects were noted. Statistical analyses were performed using nonparametric tests. Subjects' average age was 56 years, with a median low-back pain duration of 16 years. There were no significant differences in the baseline median-pain scores among injection types. The baseline and best cerebrospinal fluid-pain scores were significantly different, suggesting a placebo effect. The best pain scores for fentanyl and lidocaine were superior to their own baseline levels and to the best cerebrospinal fluid scores.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421738 TI - Chronic back pain: view from a psychiatrist's office. AB - Twenty-six adult outpatients suffering from chronic back pain were observed in a clinical study. Treatment was multifaceted. A psychiatrist with a subspecialty in pain management served as the coordinator of all treatments used. Treatment included biofeedback, physical therapy, behavioral-management program and pain measurement scales, psychotherapy with pain counseling, and medication. Patients were seen weekly for 4 months and observed for 1 year thereafter. Results of the study bore out the necessity of a coordinated multifaceted approach to treatment of chronic pain. Strong emotional overlay was seen in all patients. Stress, depression, and secondary gain are symptoms that were addressed along with the physical symptomatology. Patients improved significantly. The psychiatric component serving as the anchor for treatment was viewed as a key to success. The emotional component present in chronic pain must not be overlooked, because it plays a vital role in successful treatment. PMID- 1421739 TI - Voices from the past: ancient views of pain in childhood. AB - Our understanding of pain in childhood has made many important advances in the past 15-20 years. Examination of the views of ancient writers, who were concerned about pain and disease in childhood, reveals similar concerns that have dominated the discussions of clinicians and researchers in the twentieth century. The most recent pediatric pain research confirms the position of many writers in previous centuries who believed children and infants are sensitive to pain. Although childhood historians have assumed that pain in children was largely ignored in previous centuries, examination of ancient medical writings reveals ongoing debates about the sources of pain in childhood, symptoms of pain and its treatment. This paper contrasts historical perspectives with the views of twentieth century writers. PMID- 1421740 TI - A case of opiate-insensitive pain: malignant treatment of benign pain. AB - OBJECTIVE: We report the case of a woman with presumed cancer pain treated with escalating doses of opiates despite no evident improvement in her pain and several deleterious side effects. PATIENT: A 62-year-old woman with cervical myelopathy and a diagnosis of a spinal cord tumor was referred to the University of Washington Medical Center complaining of chest tightness, multiple joint pains, nausea, constipation, seizures and a deteriorating memory. At the time of admission she was confined to her bed with a full-time attendant and was receiving 240 milligrams of intravenous morphine per hour for her pain. INTERVENTION: Diagnostic studies failed to find any evidence of neoplasm and revealed only an old hemorrhage within the cervical spinal cord. A program of increasing physical and occupational therapy and decreasing opiate intake was initiated. RESULTS: Within a month the patient's pain complaints decreased, as did the rest of her presenting complaints. Her activities of daily living greatly increased making attendant care no longer necessary. CONCLUSIONS: This case report illustrates some of the hazards of opioid therapy in the management of patients with chronic pain. Our patient's opiate therapy was expensive, gave her undesirable side effects, and did not reduce her pain complaints or improve her function. In the treatment of chronic pain, of noncancerous or cancerous origin, a) systemic opioids may not be effective in reducing pain complaints in every patient, b) treatment efficacy evaluation should always include functional endpoints, and c) nonefficacious treatments should not be continued indefinitely. PMID- 1421741 TI - RSD score: criteria for the diagnosis of reflex sympathetic dystrophy and causalgia. AB - No standardized criteria for the diagnosis of reflex sympathetic dystrophy (RSD) are in common use. An RSD score scoring system of diagnostic criteria is proposed. Diagnosis of reflex sympathetic dystrophy by RSD score correlated well with clinical diagnosis in a group of 25 patients who had treatment for chronic upper extremity pain. Standardization of diagnostic criteria with the RSD score should enhance comparison of the outcomes of studies concerning the treatment of RSD. PMID- 1421742 TI - Interscalene blocks for chronic upper extremity pain. AB - A study of 25 patients was carried out to determine the efficacy of interscalene block (ISB) for the treatment of chronic upper extremity pain. An RSD score was used to categorize these patients. Seventeen of the 25 patients had less pain after ISB, and 14 also had increased range of motion of the affected limb. Patients with reflex sympathetic dystrophy (RSD)/causalgia, as well as other chronic pain conditions, improved. ISB was compared with stellate ganglion block (SGB) in patients undergoing both treatments. ISB seemed to be at least as effective as SGB for treatment of RSD/causalgia and may have some advantages over SGB. The role of somatic and sympathetic blockade is discussed. PMID- 1421743 TI - Reflex sympathetic dystrophy of the stump in below-knee amputees. AB - OBJECTIVE: To document the occurrence of reflex sympathetic dystrophy of the stump in two patients with below-knee amputation. DESIGN: A retrospective survey emphasising two clinical case reports. SETTING: Department of orthopaedic rehabilitation at a teaching rehabilitation hospital. PATIENTS: Lower limb amputees (n = 164) were accepted for prosthetic rehabilitation. Twenty-one amputees were regarded as rehabilitation failures; in two below-knee amputees intractable pain was the major problem. RESULTS: Clinical manifestations, radiological, and scintigraphic findings in the two amputees with intractable pain met the criteria for diagnosis of reflex sympathetic dystrophy. CONCLUSIONS: Reflex sympathetic dystrophy of the stump should be suspected in below-knee amputees whenever severe pain persists over a period of 3 to 4 months following amputation. PMID- 1421744 TI - Physical illness and the family emotional system: psoriasis as a model. AB - Most physical illnesses are characterized by significant variability in age of onset and severity of clinical course. Although many diseases may occur in the context of a strong family history for the disease, they may also occur when there is no such history. Psoriasis has been chosen as a model for demonstrating that variability in age of onset, clinical course, and family history for a given disease may be explained, in part, by factors related to the family emotional system, a concept described by family systems theory (Bowen theory). Links between the clinical manifestations of psoriasis and the family emotional system have important treatment implications. PMID- 1421745 TI - Coping with inner feelings and stress: heavy alcohol use in the context of alexithymia. AB - The authors conducted a population study to assess the relationship between heavy alcohol consumption and alexithymia, defined as difficulty in identifying and expressing feelings. The study sample consisted of 2,297 middle-aged men from eastern Finland. The proportion of men who reported either frequent intoxication or unpleasant aftereffects of heavy drinking increased linearly with alexithymia. Alexithymia and the heavy acute intake of different sorts of alcoholic drinks were also consistently associated. Long-term heavy use, taking into account both the dose and frequency, was also linearly related to the alexithymia measure. In multivariate models to assess whether high alcohol consumption in alexithymic individuals might relate to stress, the authors found nothing to support the stress-dampening hypothesis. PMID- 1421746 TI - Psychosocial antecedents of athletic injury: the effects of life stress and social support on female collegiate gymnasts. AB - The article presents information from two studies of a research program investigating psychosocial antecedents of athletic injury. Study 1 describes the development of the Life Events Survey for Collegiate Athletes (LESCA). The LESCA demonstrated good content validity and provided a stable measure of life stress. The LESCA's validity and the moderating effects of social support were explored in the second study. The LESCA provided a construct-valid measure of life stress and was a better predictor of athletic injury than the Social and Athletic Readjustment Rating Scale. Social support moderated the stress-injury relationship in such a way that LESCA negative life stress accounted for 11% to 22% of injury variances in low-support conditions; LESCA positive life stress accounted for 14% to 20% of injury variances in high-support conditions. Mechanisms underlying the stress-injury relationship and directions for future research are discussed with respect to the model outlined by M. B. Andersen and J. M. Williams in 1988. PMID- 1421747 TI - Emerging products for glycosylation analysis. PMID- 1421748 TI - Mammalian glycosyltransferases: genomic organization and protein structure. AB - In recent years, several glycosyltransferase genes and cDNAs have been cloned and characterized. Although the glycosyltransferases seem to share the same general architecture, there is only little sequence similarity between the various enzymes. Moreover, a comparison of the organization of the genes shows that there is no common pattern of intron-exon structure. In addition, there seems to be little or no correlation between glycosyltransferase exons and protein domains. Taken together, these observations suggest that many of the glycosyltransferase genes evolved independently. So far, only two glycosyltransferase gene families have been described. These families may have evolved by exon-shuffling, or by gene duplication and subsequent divergence. For specific glycosyltransferases, mechanisms such as alternative splicing and alternative promoter usage play a role in the production of multiple protein isoforms from a single gene. These isoenzymes may differ in their enzymatic properties or cellular localization. PMID- 1421749 TI - Photoaffinity labelling of glycosyltransferases. AB - The photoaffinity analogues 5-azido-UDP-glucose and 5-azido-UDP-glucuronic acid have proven to be valuable biochemical tools in the studies of nucleoside diphosphate sugar-utilizing enzymes, especially membrane-associated glycosyltransferases. A summary of the past and current uses of these analogues is presented, as well as photoaffinity data for the enzyme UDP-glucose: dolichylphosphate glucosyltransferase (Glc-P-Dol synthase). This enzyme has served as a model membrane-associated glycosyltransferase for demonstrating the uses of 5-azido-UDP-glucose. The advantages of using photoaffinity analogues for the purification and characterization of glycosyltransferases are presented, as well as an outline of the general procedures which can be used in conjunction with these analogues. PMID- 1421750 TI - Identification and synthesis of a novel 15 kDa beta-galactoside-binding lectin in human leukocytes. AB - Knowledge of the identity, synthesis and secretion of beta-galactoside-binding lectins by leukocytes is of importance because lactosaminoglycans present at the leukocyte cell surface may be physiologically significant lectin receptors that could mediate autocrine or paracrine functions and/or cell adhesion. This paper presents data that show that a previously identified 15.5-16.5 kDa lactose binding protein synthesized in vitro by human peripheral leukocytes is actually comprised of three different polypeptides. One of these is related to a novel 15 kDa lectin isolated from human spleen and which is synthesized by B lymphoblastoid cells. Spleen contains at least six lactose-binding polypeptides for which the carbohydrate-binding activity is independent of the presence of divalent cations and mercaptoethanol. The splenic 15 kDa polypeptide does not appear to be immunologically related to previously characterized beta-galactoside binding lectins. It is separable from galaptin, another galactoside-binding lectin (subunit mol. wt 14.5 kDa) by chromatography on DEAE-Sephacel. Western blot analyses and immunoprecipitation/fluorography experiments with metabolically labelled cells showed the presence of the 15 kDa lectin in peripheral leukocytes and in Epstein-Barr virus-immortalized B lymphoblastoid cells. The 15 kDa lectin yielded polypeptide fragments of approximately 6.2 and approximately 8.6 kDa after cyanogen bromide (CNBr) degradation. These fragments were partially sequenced and 12 residues/fragment were identified. A similarity search of the SWISS PROT protein data base did not reveal a relationship of the 15 kDa polypeptide to known lectins, including galaptin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421751 TI - Reducing the overlap problem in the proton NMR spectra of oligosaccharides by application of pseudo-four-dimensional homonuclear HOHAHA-HOHAHA-COSY. AB - A new homonuclear NMR experiment is described for the assignment of the proton NMR spectra of oligosaccharides, namely HOHAHA-HOHAHA-COSY (where HOHAHA is homonuclear Hartmann-Hahn spectroscopy and COSY is correlated spectroscopy). While this technique may formally be thought of as a four-dimensional NMR experiment, by use of selective pulses it is demonstrated that the analogous pseudo-four-dimensional experiment is a valuable improvement over conventional three-dimensional HOHAHA-COSY, in that the degree of resonance overlap is markedly reduced by the dispersion of resonances into a fourth effective dimension. The technique is demonstrated by application to the biantennary nonasaccharide Gal beta 1-4-GlcNAc beta 1-2Man alpha 1-6(Gal beta 1-4GlcNAc beta 1-2Man alpha 1-3)Man-beta 1-4GlcNAc beta 1-4GlcNAc. PMID- 1421752 TI - Carbohydrate structure of Marburg virus glycoprotein. AB - Marburg virus was propagated in E6 cells, a cloned cell line of Vero cells, in the presence of [6-3H]glucosamine. Radiolabelled viral glycoprotein was digested with trypsin, and oligosaccharides were liberated by sequential treatment with endo-beta-N-acetylglucosaminidase H, peptide-N4-(N-acetyl-beta glucosaminyl)asparagine amidase F and O-glycosidase, by beta-elimination, and by alkaline hydrolysis. After fractionation by HPLC and gel filtration, glycans were characterized chromatographically, by digestion with exoglycosidases and, in part, by methylation analysis and liquid secondary ion mass spectrometry. The oligosaccharide structures thus established include oligomannosidic and hybrid type N-glycans, as well as neutral fucosylated bi-, tri- and tetraantennary species, most of which carry an additional bisecting N-acetylglucosamine. In addition, high amounts of neutral mucin-type O-glycans with type-1 and type-2 core structures were detected. None of the glycans present in this viral glycoprotein carried sialic acid residues. PMID- 1421753 TI - The tertiary structure of endo-beta-1,4-glucanase B (CenB), a multidomain cellulase from the bacterium Cellulomonas fimi. AB - Endo-beta-1,4-glucanase B (CenB) is a large (110 kDa) extracellular enzyme from the cellulolytic bacterium Cellulomonas fimi. CenB contains five domains, including a typical C.fimi cellulose-binding domain, separated by distinctive linker polypeptides (Meinke et al., 1991b). X-ray scattering analyses show that CenB has a highly elongated shape resembling beads on a string. The sizes of the polypeptides produced by treatment of CenB with proteases, together with their N terminal amino acid sequences, show that at least two of the four linkers connecting the five domains of CenB are more sensitive to proteolysis than the domains themselves. It is concluded that the beads represent the domains of CenB, the string represents the linkers. PMID- 1421754 TI - A human lysosomal alpha(1----6)-mannosidase active on the branched trimannosyl core of complex glycans. AB - Normal human fibroblasts and fibroblasts from a patient with alpha-mannosidosis were grown in the presence or absence of 100 microM swainsonine for 7 days. Accumulated oligosaccharides were isolated and analysed by high performance liquid chromatography (HPLC) and methylation analysis. Man alpha 1----3Man beta 1 ---4GlcNAc and Man alpha 1----2Man alpha 1----3-Man beta 1----4GlcNAc (where Man is D-mannose and GlcNAc is N-acetyl-D-glucosamine) comprised greater than 80% of the total oligosaccharides in untreated mannosidosis cells. However, Man alpha 1- --6[Man alpha 1----3]Man beta 1----4GlcNAc was the major Man3GlcNAc isomer present after 7 days of swainsonine treatment. No mannose-containing oligosaccharides were detected in control fibroblasts in the absence of swainsonine but, in its presence, oligosaccharides containing 2-9 mannose residues accumulated. Man alpha 1----6[Man alpha 1----3]-Man alpha 1----6[Man alpha 1----3]Man beta 1----4GlcNAc and Man alpha 1----6-[Man alpha 1----3]Man beta 1----4GlcNAc were the major components (67%). Surprisingly, Man alpha 1--- 3Man beta 1----4GlcNAc was only observed in swainsonine-treated control cells during the recovery period after removal of swainsonine. These studies suggest the presence of a second lysosomal alpha-mannosidase activity which is unaffected in genetic alpha-mannosidosis, but is inhibited by swainsonine. This enzyme would cleave the alpha(1----6)-linked mannose residue from branched Man3GlcNAc to form Man alpha 1----3Man beta 1----4GlcNAc. To confirm this hypothesis, fractions from alpha-mannosidosis and control fibroblasts that bound to concanavalin A (ConA) Sepharose and were eluted with 0.5 M alpha-methyl mannoside were incubated at pH 4.0 with Man alpha 1----6[Man alpha 1----3]Man beta 1----4-GlcNAc. As anticipated, Man alpha 1----3Man beta 1----4GlcNAc was the sole product using enzyme from mannosidosis fibroblasts, while the major product from control fibroblasts was Man alpha 1----6Man beta 1----4GlcNAc. This confirmed the presence of a swainsonine-inhibitable alpha(1----6)-mannosidase activity unaffected by the disease. The differing substrate specificities of the alpha(1-- -6)-mannosidase and the major lysosomal alpha-mannosidase indicate that the alpha(1----6)-mannosidase plays an important role in the generation of the oligosaccharides accumulated in alpha-mannosidosis patients. PMID- 1421755 TI - Developmental sialic acid modifications in rat organs. AB - The changes in expression of sialic acids in Sprague-Dawley rats in the prenatal and early postnatal time period have been examined in multiple organs, both visceral and non-visceral. In all organs examined, there is a dramatic increase in both N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) shortly after birth. The bulk of the sialic acid is present in the ganglioside fraction in all tissues examined. As total amounts of sialic acid present in gangliosides decrease, the proportion present in the low molecular weight cytosolic fraction increases. A curious observation is that Neu5Ac hydroxylase activity is present at the time of the increase in sialic acid, but its activity does not correlate with Neu5Gc expression after the early postnatal period. This implies that Neu5Gc expression has another level of regulation besides CMP-Neu5Ac hydroxylase activity. PMID- 1421756 TI - Presence of O-linked oligosaccharide on a threonine residue in the human transferrin receptor. AB - We have previously demonstrated that the human transferrin receptor (TfR) of approximately 90 kDa contains Ser/Thr-linked (O-linked) oligosaccharides. In the present study, we report our identification of the site of attachment of the O linked oligosaccharides in the receptor. A 70 kDa fragment from the external domain of the TfR was generated by trypsin treatment of the [3H]glucosamine labelled receptor purified from human K562 cells. The beta-elimination of the intact TfR, but not the 70 kDa fragment, released Gal-[3H]Gal-NAcitol, indicating that the 70 kDa fragment lacks O-linked oligosaccharides. In the remaining 20 kDa fragment there are three potential sites (Thr96, Thr104 and Ser106) for O glycosylation in the extracellular domain. To identify which of these residues are O-glycosylated, both the [3H]Thr- and [3H]Ser-labelled TfR were directly treated with mild base to effect beta-elimination, and the radiolabelled amino acids and their derivatives were analysed. Approximately 2% of the total radiolabelled Thr, but no radiolabelled Ser, was converted to expected beta elimination products by this treatment. These and other results demonstrate that only one O-linked oligosaccharide is present in the TfR and that it occurs on either Thr96 or Thr104. From human serum we purified the cleaved, soluble form of the TfR (s-TfR), which contains Thr104, but lacks Thr96. The s-TfR was sensitive to O-glycanase and bound to Jacalin lectin, indicating that the s-TfR contains an O-linked oligosaccharide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421757 TI - Identification of the O-linked glycosylation site of the human transferrin receptor. AB - The human transferrin receptor is a glycoprotein containing three N-linked and one O-linked glycosylation sites. Tryptic digestion of the receptor, followed by chromatography on BioGel P-2 and reverse-phase HPLC, yields a glycopeptide (amino acids 101-120) containing the O-linked site. Amino acid sequence analysis reveals that the site of O-glycosylation is Thr-104. Mass spectral analysis is consistent with the presence of a Gal-GalNAc core with predominantly two sialic acid residues. PMID- 1421758 TI - Topology of ER processing alpha-mannosidase of Saccharomyces cerevisiae. AB - The yeast specific alpha-mannosidase which converts Man9GlcNAc to a single isomer of Man8GlcNAc is involved in N-linked oligosaccharide processing in the endoplasmic reticulum (ER). Sequence analysis of the structural gene for this enzyme suggested that it is a type II transmembrane protein (Camirand et al., 1991). To firmly establish its membrane topology, the gene was transcribed in vitro and translation was performed in a reticulocyte lysate with and without dog pancreas microsomal membranes. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of [35S]methionine-labelled products showed that the largest band formed corresponded in size to the 63 kDa peptide expected from the alpha-mannosidase gene product. It was transformed into a 4 kDa larger endoglycosidase H-sensitive band in the presence of microsomal membranes. This glycosylated translation product was completely protected from proteinase K digestion in the absence of detergent. These results demonstrate that the yeast ER alpha-mannosidase is a type II membrane protein, like Golgi enzymes involved in N-linked glycosylation. PMID- 1421759 TI - Cloning and expression of the murine gene and chromosomal location of the human gene encoding N-acetylglucosaminyltransferase I. AB - A mouse cDNA clone previously isolated from an F9 teratocarcinoma cell library and shown to confer N-acetylglucosaminyltransferase I (GlcNAc-TI) activity on Lec1 Chinese hamster ovary (CHO) cell transfectants [Kumar, R., Yang,J., Larsen,R.D. and Stanley,P. (1990) Proc. Natl. Acad Sci. USA, 87, 9948-9952] has been sequenced. The nucleotide and deduced amino acid sequences are highly homologous to previously described human and rabbit GlcNAc-TI cDNAs. A 1250 bp portion of the mouse cDNA encoding all but the first 34 amino acids of the deduced protein sequence was inducibly expressed in Escherichia coli and gave rise to a prominent fusion protein of mol. wt approximately 45 kDa whose presence correlated with high levels of GlcNAc-TI activity in cell lysates. Probes generated from the cDNA were used to show that the GlcNAc-TI gene is present in a single copy in mammals and that a homologous gene was not detectable (under low stringency hybridization conditions) in DNA from yeast, sea urchin, Drosophila or Chaenorhaditis elegans. Genomic DNA clones that hybridized to probes generated from the GlcNAc-TI cDNA were isolated from a mouse liver library. Restriction analyses, Southern hybridization and DNA sequence analyses of subcloned genomic DNA fragments and a polymerase chain reaction (PCR) product provided evidence that the coding and 3' untranslated regions of the cDNA reside in a single exon. However, the mouse GlcNAc-TI gene (Mgat-1) includes at least one additional exon 5' of the coding region. Southern analyses of DNA from mouse-human somatic cell hybrids and in situ hybridization were used to locate the human GlcNAc-TI gene (MGAT-1) between positions q31.2 and q31.3 on chromosome 5, a region of chromosome 5 that is syntenic with a region of mouse chromosome 11. Northern analyses of adult mouse tissues revealed two GlcNAc-TI gene transcripts that are differentially expressed in different tissues. PMID- 1421760 TI - Fingerprinting genomes by use of PCR with primers that encode protein motifs or contain sequences that regulate gene expression. AB - PCR primers of arbitrary nucleotide sequence have identified DNA polymorphisms useful for genetic mapping in a large variety of organisms. Although technically very powerful, the use of arbitrary primers for genome mapping has the disadvantage of characterizing DNA sequences of unknown function. Thus, there is no reason to anticipate that DNA fragments amplified by use of arbitrary primers will be enriched for either transcribed or promoter sequences that may be conserved in evolution. For these reasons, we modified the arbitrarily primed PCR method by using oligonucleotide primers derived from conserved promoter elements and protein motifs. Twenty-nine of these primers were tested individually and in pairwise combinations for their ability to amplify genomic DNA from a variety of species including various inbred strains of laboratory mice and Mus spretus. Using recombinant inbred strains of mice, we determined the chromosomal location of 27 polymorphic fragments in the mouse genome. The results demonstrated that motif sequence-tagged PCR products are reliable markers for mapping the mouse genome and that motif primers can also be used for genomic fingerprinting of many divergent species. PMID- 1421761 TI - Modulation of polymorphic loci detection with synthetic tandem repeat variants. AB - The modifications of hybridization patterns were studied when Southern blots, carrying stallions DNA samples, were probed with eight synthetic tandem repeats (STRs), related by sequence variations in the basic unit. Because STRs preferentially crosshybridize with genomic VNTRs, they usually give patterns looking more like DNA fingerprints, but we found that even small modifications in the STR monomer could cause major changes in the hybridization profiles and could induce a shift of fingerprint pattern towards the detection of only one or two loci. This enables the use of STRs as direct genetic markers for linkage analysis, without cloning of the corresponding DNA fragment. Moreover, the set of STR variants can suggest consensus sequences allowing some prediction of the banding pattern. PMID- 1421762 TI - A mouse genomic library in the bacteriophage P1 cloning system: organization and characterization. AB - Using the bacteriophage P1 cloning system, we have constructed a two to three times coverage, high-molecular-weight (HMW) genomic library from mouse C127 fibroblast cells. The library consists of about 127,500 clones with an average insert size of about 70 kb that are organized into 300 primary pools containing approximately 425 clones per pool. For screening purposes the primary pools are combined into secondary pools (approximately 4250 clones each) and tertiary pools (approximately 21,250 clones each). Screening is performed by the polymerase chain reaction (PCR) with DNA isolated from the secondary and tertiary pools. We have screened the library for 13 different mouse sequences and have detected 11. Clones generated from two of the eleven positive screens were isolated from the library (those containing the c-fos and G alpha i2 genes) and were further characterized. Direct double-stranded sequencing of DNA from P1 clones with primers bordering the insert provided sequence information from each end of the cloned DNA. PMID- 1421763 TI - RASA contains a polymorphic microsatellite and maps to bovine syntenic group U22 on chromosome 7q2.4-qter. AB - The bovine gene for the p21ras protein activator (RASA) includes in its 5' untranslated region a (TG)n repeat. Analysis of this (TG)n repeat by PCR amplification of genomic DNA revealed a four-allele polymorphism. A cDNA probe was used to assign RASA to the region 2.4-qter of bovine Chromosome (Chr) 7 by in situ hybridization. PCR analysis of a panel of somatic hybrid lines allowed the assignment of RASA to the unassigned syntenic group 22 (U22) and thus localizes U22 on Chr 7. PMID- 1421764 TI - Polymorphic microsatellite loci of the rat (Rattus norvegicus). AB - The EMBL and GenBank DNA databases were searched for microsatellite sequences of the rat containing dinucleotide repeats of (CA)n and (GA)n. Among those obtained, 23 sequences were analyzed by polymerase chain reaction to examine the size variation of the amplified fragment in inbred rat strains. All of the 23 microsatellite sequences varied in size among the strains tested. The 23 microsatellite loci in a pair of substrains separated from the same progenitor strain were then analyzed. Fragments identical in size were observed in all loci of the two substrains, indicating the stability of the microsatellite over a large number of generations. The microsatellite loci, therefore, should be useful markers for linkage analyses in the rat. PMID- 1421765 TI - Deletion mapping of the mouse ornithine decarboxylase-related locus Odc-rs8 within Igh-V. AB - The Odc-rs8 locus belongs to a family of mouse DNA sequences related to the gene encoding ornithine decarboxylase (ODC). Odc-rs8 was mapped by recombinant inbred (RI) strain analysis to the region of Chromosome (Chr) 12 occupied by the variable region genes of the immunoglobulin heavy chain (Igh) complex. In the present study, alleles at Odc-rs8 were shown to cosegregate with those for Igh variable region (Igh-V or VH) genes among 37 inbred mouse strains that had been characterized previously for their haplotypes at Igh. For a more precise definition of the location of Odc-rs8 relative to Igh-V, DNAs from 17 Abelson murine leukemia virus (A-MuLV)-transformed pre-B cell lines cultured from mice heterozygous at Igh and Odc-rs8 were analyzed for the presence of DNA restriction fragments (RFs) derived from each parental Odc-rs8 allele. These cell lines, each of which has rearranged one or both Igh genes, previously were employed in mapping members of nine VH gene families by deletion analysis (Brodeur et al. 1988). Comparing the deletion profiles of the cell lines for Odc-rs8 with those for the VH gene families has located Odc-rs8b within the VHJ558/VH3609 gene cluster and Odc-rs8c either within or upstream of the 5'-most 9% of VHJ558, identifying Odc-rs8 as a potentially useful marker for the 5' end of the Igh complex. PMID- 1421766 TI - Syntenic mapping and chromosomal localization of bovine alpha and beta interferon genes. AB - The previous assignment of bovine alpha-(IFNA) and beta-(IFNB) interferon gene families to syntenic group U18 was confirmed with additional cDNA probes and a bovine-rodent hybrid somatic cell panel representing all 29 bovine autosomal syntenic groups. Fluorescent in situ hybridization (FISH) localized these genes to bovine Chromosome (Chr) 8 band 15 and demonstrates that with biotinylated plasmids, as few as five tandemly arrayed sequences can be detected by conventional fluorescent microscopy. This technique can be applied to physical mapping of other multicopy genes in domestic animals. PMID- 1421767 TI - Functional analysis of a t complex responder locus transgene in mice. AB - Transmission ratio distortion (TRD) of mouse t haplotypes occurs through the interaction of multiple distorter loci with the t complex responder (Tcr) locus. Males heterozygous for a t haplotype will transmit the t-bearing chromosome to nearly all of their offspring. This process is mediated by the production of functionally inequivalent gametes: wild-type meiotic partners of t spermatozoa are rendered functionally inactive. The Tcr locus, which is required for TRD to occur, is thought to somehow protect its host spermatid from the sperm inactivating effects of linked distorter genes (Lyon 1984). In previous work, Tcr was mapped to a small genetic interval in t haplotypes, and a candidate gene from this region was isolated (Tcp-10bt). In this work, we further localize Tcr to a 40-kb region that contains the 21-kb Tcp-10bt gene. A cloned genomic copy of Tcp 10bt was used to generate transgenic mice. The transgene was bred into a variety of genetic backgrounds to test for non-Mendelian segregation. Abberrant segregation was observed in some mice carrying either a complete t haplotype or a combination of certain partial t haplotypes. These observations, coupled with those of Snyder and colleagues (in this issue), provide genetic and functional evidence that the Tcp-10bt gene is Tcr. However, other genotypes that were predicted to produce distortion did not. The unexpected data from a variety of crosses in this work and those of our colleagues suggest that elements to the TRD system and the Tcr locus remain to be identified. PMID- 1421769 TI - Linkage analysis of the Gi alpha 2 gene on mouse chromosome 9. PMID- 1421770 TI - Four-state models and regulation of contraction of smooth muscle. I. Physical considerations, stability, and solutions. AB - Cyclic four-state models are frequently used in biology to represent a variety of molecular behaviors. A common experimental strategy to test such models is to follow the behavior of the real system after some of the rate constants are changed in a stepwise manner. We analyze the mathematical behavior of a simple example of such a model applicable to the regulation of contraction of smooth muscle, but our results apply in general to any linear, cyclic four-state model. We discuss detailed balance and requirements for linearity. We find that the only way to have sustained oscillations is for the rate constants of the model to be themselves oscillatory. We state conditions for decaying oscillations and find that in models that do not follow strictly first-order kinetics and do not satisfy detailed balance, these conditions can hold. We show analytically that the response of any state to step changes in the rate constants is the sum of three weighted exponentials plus a constant term, the steady-state value. We provide explicit expressions for the time dependence of all state variables. We discuss a simple way to use these results to obtain numerical solutions in cases where the rate constants change in an arbitrary way. PMID- 1421768 TI - Distortion of transmission ratio by a candidate t complex responder locus transgene. AB - The mouse t complex responder locus (Tcr) is centrally involved in the phenomenon of male-specific transmission ratio distortion (TRD) through its action in haploid germ cells. Previously, we identified a candidate gene, Tcp-10b, whose t allele generates alternatively spliced transcripts. The full-length Tcp-10bt transcript is present in pre- and postmeiotic germ cells and encodes a product that is virtually identical with that encoded by the wild-type allele. The alternatively spliced t-specific transcript is observed in post-meiotic haploid spermatids and would encode an altered polypeptide that could convey the Tcrt phenotype. To assess their function, we have introduced constructs representing each Tcp-10bt transcript into transgenic mice. Breeding experiments demonstrate that these two constructs alter the transmission ratios of t haplotypes from male mice, but in opposite directions. The results provide support for the hypothesis that Tcp-10bt is a component of the Tcr locus. PMID- 1421771 TI - An analysis of life history evolution in terms of the density-dependent Lefkovitch matrix model. AB - The evolution of demographic characteristics is considered in terms of the density-dependent Lefkovitch matrix model, which describes a species' population dynamics with a stage-specific pattern of reproduction and mortality. We obtain the invadability condition of a mutant-type into the wild-type population at the equilibrium state. The condition depends on the left and right eigenvectors at the equilibrium state. The condition depends on the left and right eigenvectors at the equilibrium state and the difference, between wild-type and mutant-type populations, of the values of elements in the Lefkovitch matrix at the equilibrium state. It is also shown that if elements of the density-dependent Lefkovitch matrix are decreasing functions of population density, then the equilibrium population density increases in the process of natural selection; that is, K-selection acts even on the stage-structured population. The evolution of life history in perennial plants is discussed through two models as an application of the above results. The evolution of perennial plants with no vegetative reproduction is analyzed in the first example. It is shown that whether monocarpic perennials (which reproduce once and die) or polycarpic perennial plants (which reproduce more than once) are favored depends on the cost of a produced seed. The second example concerns perennial plants that reproduce vegetatively. It is shown that whether monocarpic or polycarpic perennial plants are favored depends on the cost of a seed and that where vegetative reproduction is common, polycarpic perennials with no seed reproduction are favored. PMID- 1421772 TI - The possible effects of aggregation on the quantitative interpretation of flow patterns in ecological networks. PMID- 1421773 TI - Nature is not uniform. PMID- 1421774 TI - Four-state models and regulation of contraction of smooth muscle. II. Properties of the solutions and identification. AB - We analyze the behavior and the identification problem of cyclic four-state models. We find that for any state, or a weighted combination of two states, there can be at most one maximum, or one minimum, and two inflection points. We obtain necessary conditions for overshoot and undershoot and give examples. We describe procedures to estimate all the rate constants and discuss certain experimental aspects of the identification problem. Finally, we give an example of identification by obtaining the 10 model parameters from experimental data on skinned fibers from smooth muscle. These results, in conjunction with the results of the previous paper, can help in testing four-state models of regulation of contraction of smooth muscle and of a variety of other physiological and biochemical phenomena. PMID- 1421775 TI - Improving Tikhonov regularization with linearly constrained optimization: application to the inverse epicardial potential solution. AB - Two methods to improve on the accuracy of the Tikhonov regularization technique commonly used for the stable recovery of solutions to ill-posed problems are presented. These methods do not require a priori knowledge of the properties of the solution or of the error. Rather they exploit the observed properties of overregularized and underregularized Tikhonov solutions so as to impose linear constraints on the sought-after solution. The two methods were applied to the inverse problem of electrocardiography using a spherical heart-torso model and simulated inner-sphere (epicardial) and outer-sphere (body) potential distributions. It is shown that if the overregularized and underregularized Tikhonov solutions are chosen properly, the two methods yield epicardial solutions that are not only more accurate than the optimal Tikhonov solution but also provide other qualitative information, such as correct position of the extrema, not obtainable using ordinary Tikhonov regularization. A heuristic method to select the overregularized and underregularized solutions is discussed. PMID- 1421776 TI - Structured modeling of fish physiology. AB - The use of models in simulation and state estimation has proved useful in diverse applications, especially in industrial process control. The project presented here looked into the modeling of fish physiology for applications in fish physiology research and aquaculture. The models deal with gastric evacuation, metabolism, kidneys, gills, the cardiovascular system, and feeding behavior and are based on data from the literature. Model responses are mostly in accord with real responses in principle, but, as with most models of complex biological systems, the numerical accuracy is low in several cases. However, these structured models enable researchers to test hypotheses by altering the submodels and parameters. PMID- 1421777 TI - Branched-chain amino acids and respiration. AB - A series of investigations suggest a specific role for BCAA in the regulation of respiration. In vitro incubation studies have shown that BCAAs improve the recovery of muscle force after fatigue. Further investigations revealed that leucine plays a key role in this action and acts in a manner not dependent on its use as an energy substrate. In humans, solutions enriched with BCAA have decreased PCO2 and stimulated the ventilatory response to hypercapnia, thereby corresponding to an enhanced ventilatory sensitivity with the administration of BCAA. The mechanisms for these actions are unknown. The most viable hypothesis is based on the ability of BCAA to decrease the synthesis of serotonin due to altered transport of AAs, including tryptophan, to the brain. Clinical studies have suggested a potency of BCAA in the treatment of respiratory dysfunction of preterm infants, as well as of patients with sleep apnea related to various disease states. The clinical applications of BCAA-enriched mixtures in respiratory diseases are still experimental, and many controversies exist concerning the validity of BCAA in clinical practice. Most TPN regimens contain BCAA approximating the average intake of BCAA in the Western diet. The question therefore remains whether additional BCAA supplementation is useful to achieve the suggested metabolic and pharmacological effects. Meticulous future studies are needed to establish the therapeutic value of BCAA in the treatment of various respiratory functions. PMID- 1421778 TI - Management of diabetic patients requiring nutritional support. AB - A retrospective analysis was performed on 70 patients with diabetes mellitus who required nutritional support over the 10-yr period 1979-1989. Information was available for 65 patients, of whom 55 had non-insulin-dependent diabetes mellitus (NIDDM). Enteral nutrition (EN, 750-2200 kcal/day) was given to 40 NIDDM patients (group A) and 6 insulin-dependent diabetic (IDDM) patients (group B), and parenteral nutrition (PN, 1600-2400 kcal/day) was given to 18 NIDDM patients (group C) and 4 IDDM patients (group D). Three NIDDM patients required both types of feeding. Preadmission diabetes treatment remained the same during feeding for 31% of the total group (38% of group A, 33% of group B, 23% of group C, and 0% of group D). The NIDDM patients in group C who received insulin during PN required a high daily dose of approximately 100 U. The IDDM patients on PN required an increase of 225% from their preadmission daily dose. The likelihood of a patient requiring a major change from preadmission diabetes therapy depended mainly on the severity of the underlying illness and on the type of feeding (greater with PN) but not on preadmission therapy, age of patient, or type of EN (cyclic vs. continuous). Hypoglycemic episodes were uncommon in all groups. There were no significant differences between the prefeeding and feeding blood glucose levels and HbA1c results. PMID- 1421779 TI - Performance of normal-weight and underweight men with marginal changes in energy intake. AB - This study compares the continuous response of six underweight (UW) (body mass index [BMI] < 18 kg/m2) and six normal-weight (NW) (20 < BMI < 25) men of similar age to a modest but sustained level of underfeeding and overfeeding. Habitual energy intake over 4 wk, body composition, and basal metabolic rate (BMR) were measured under metabolic-ward conditions. NW subjects were heavier by 9 kg and had 5% more body fat than UW subjects. The average BMR of UW subjects was 7.5% lower than NW subjects in absolute terms and also per kilogram fat-free mass per day but was higher by 8% when expressed per kilogram body weight per day. Three NW and three UW subjects were given a diet with 10% less energy than their habitual intake for 4 wk. They were brought back to the normal level of feeding for another 4 wk. Finally, they were overfed by 10% for 4 wk. This sequence was reversed in the remaining six subjects. Changes in body weight, BMR, and energy balance were assessed. UW subjects showed a quick and vigorous reduction in BMR (13.4%) during the 1st wk of underfeeding compared with NW subjects (8.1%). In the later weeks, the reduction was 8% in UW and 7% in NW subjects. Furthermore, UW subjects showed a tendency to resist a decrease in body weight (mean loss 180 g), unlike NW subjects (mean loss 730 g). With overfeeding, the mean increase in BMR for UW was higher (7.4%) than for NW (5.3%) subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421780 TI - Dietary fat level as determinant of protein-sparing actions of structured triglycerides. AB - This study assessed the effects of total parenteral nutrition (TPN) containing long-chain triglycerides (LCTs), an equimolar physical mixture of LCT and medium chain triglycerides (MCTs), and a structured triglyceride synthesized from equimolar amounts of MCT and LCT on energy and protein metabolism after thermal injury (25% body surface area full-thickness scald burn). Male Sprague-Dawley rats (245-271 g) received isovolemic diets intravenously that supplied 250 kcal.kg-1.day-1, 2 g amino acid nitrogen.kg-1.day-1, and 50% of nonprotein calories as lipid and 50% as dextrose for 3 days. Whole-body and tissue leucine kinetics were estimated by a 4-h continuous infusion of L-[1-14C]leucine on day 3. Nitrogen balance, plasma albumin, plasma glucose, energy expenditure, and whole-body and liver and rectus muscle protein kinetic parameters were determined. No significant differences were noted in any of the parameters measured. This study suggests that the unique protein-sparing actions usually associated with structured triglyceride administration are not seen when they are provided as 50% of nonprotein calories. In addition, the ratio of MCT to LCT in the starting mixture from which the structured triglycerides are synthesized may be an important determinant of the protein-sparing actions attributed to these lipids. PMID- 1421781 TI - Factorial experiment to determine influence of fish protein and fish oil on serum and liver lipids in rabbits. AB - Rabbits were fed purified diets consisting of casein (CA), fish protein (FP), and soy protein (SP) combined with MaxEpa oil (ME) or corn oil (CN) to determine the effects of dietary protein and lipid sources on serum total, lipoprotein, and hepatic lipid levels. Dietary proteins and lipids exerted significant (p < 0.05) separate effects on serum total cholesterol (TC) (p < 0.005), very-low-density lipoprotein cholesterol (VLDL-C) (p < 0.001), and high-density lipoprotein cholesterol (HDL-C) (p < 0.001), whereas only dietary proteins significantly affected low-density lipoprotein cholesterol (LDL-C) (p < 0.001) and the LDL C/HDL-C ratio (p < 0.05). Hence, FP induced serum TC (233 mg/dl), VLDL-C (22 mg/dl), and LDL-C (151 mg/dl) intermediary to hypercholesterolemic CA (TC, 319 mg/dl; VLDL-C, 57 mg/dl; LDL-C, 204 mg/dl) and cholesterol-lowering SP (TC, 129 mg/dl; VLDL-C 19 mg/dl; LDL-C, 84 mg/dl). The twofold rise in HDL-C on feeding FP (35 mg/dl), compared with CA (20 mg/dl) and SP (16 mg/dl), resulted in a drop in LDL-C/HDL-C to a level similar to that of SP groups. The cholesterol-lowering action of ME (188 mg/dl), in contrast to CN (266 mg/dl), was reflected mainly in VLDL (ME, 15 mg/dl; CN, 50 mg/dl) but also in HDL (ME, 16 mg/dl; CN, 31 mg/dl) fractions. Compared with CN, the significant (p < 0.05) ME-induced rise in serum and VLDL triglycerides was accompanied by a significant (p < 0.001) drop in lipoprotein lipase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421783 TI - New horizons in nutritional biochemistry and metabolism. PMID- 1421782 TI - Total parenteral nutrition: iatrogenic immunosuppression. AB - It may be necessary for future formulations of TPN to encompass functions other than mere provisions of nutrients. Although current solutions of TPN are well tolerated in most patients for short periods and remain an important adjunct to modern surgical therapy, these solutions have significant room for improvement. Designing the ideal artificial gut for the highly stressed patient may include reproduction of the neurological, endocrine, and immune responses that occur after the oral presentation of foodstuffs. PMID- 1421784 TI - Energy expenditure in cancer patients. PMID- 1421786 TI - The evolving story of lipids as a calorie source. PMID- 1421785 TI - Nutritional and developmental variations of intestinal glycosylation. PMID- 1421787 TI - L-arginine, nitric oxide and collagen vascular diseases: a potential relationship? PMID- 1421788 TI - The therapeutic use of L-arginine to increase nitric oxide production. PMID- 1421789 TI - The histogram and boxplot: a picture is worth a thousand words. PMID- 1421790 TI - On the cause and prevention of Kak'ke. 1885. PMID- 1421792 TI - The growing problem of osteoporosis. PMID- 1421791 TI - John M. Kinney Award. Reflections on a long term interest in energy metabolism and injury. PMID- 1421793 TI - Differences in fracture pattern between an urban and a rural population: a comparative population-based study in southern Sweden. AB - Differences in the incidence of hip fractures have been reported between urban and rural areas. In this population-based study the characteristics of fracture patterns between the city of Malmo and the nearby rural district of Sjobo were compared. A total of 782 individuals in Malmo and 486 in Sjobo were invited to participate. Fracture history for all invited was registered. The odds ratio for fracture was higher in Malmo, particularly for women over 70. More than half of the urban women aged 70 had a history of a fracture. A fourfold increase in fracture prevalence between the ages of 60 and 70 was observed in women in Malmo, whereas the prevalence doubled in Sjobo. The differences in fracture patterns between these two urban and rural communities may be explained by different lifestyles. PMID- 1421794 TI - Comparison and investigation of bone mineral density in opposing femora by dual energy X-ray absorptiometry. AB - A dual-energy X-ray absorptiometry (DXA) machine was used to measure the bone mineral density (BMD) of both femora in 760 female volunteers. Each volunteer completed a questionnaire and exclusion criteria were applied such that only 480 of these were considered normal subjects. The remaining 280 women failed to comply with the criteria and were considered 'abnormal'; their BMD results were analysed separately. Two abnormal subgroups, one with previous long bone fractures and one with radiologically diagnosed osteopenia, were studied. BMD values for femoral neck, Ward's triangle and trochanter were compared between the two femora in all the above groups. No dominance relationship was found when comparing left to right femur, averaged over any population studied, but large differences were found between the femora in individual volunteers. There was a high correlation between BMD in opposing femora of 0.91, 0.91 and 0.84 for the femoral neck, Ward's triangle and trochanter respectively. However, in normal subjects the percentage variation in these regions ranged up to 34%, 64% and 80% respectively at the different femoral sites. In addition, the normal population was divided into two subgroups, one in which the density difference between the femora was large, and the other in which the difference was statistically insignificant. The analytical and anatomical variations between these two groups were investigated. Only part of the difference appeared to be due to analytical problems and it seems that there is a genuine difference in femoral density. Poor correlation for femoral neck percentage density difference was found with average BMD, age, height and weight in the normal population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421795 TI - Epidemiology of hip fractures in The Netherlands: women compared with men. AB - In this retrospective study the epidemiology of hip fractures in The Netherlands was evaluated. The number of hip fractures over the period 1972-1987 was collected from the Dutch Centre for Health Care Information (Stichting Informatiecentrum voor de Gezondheidszorg, SIG). The demographic data were collected from the Dutch Centre for Statistics (Centraal bureau voor de Statistiek, CBS). The age-adjusted incidence of hip fractures for both women and men 50 years of age and over, increased linearly over the period 1972-1987. There was also a linear rise in the age-adjusted incidence of hip fractures in women and men 65 years of age and over, but the rise in incidence was equal in both sexes. After the age of 50 years women and men showed an equal proportional increase in the age-specific incidence of hip fractures by 5-year age groups. This proportional increase was independent of the calendar year studied during the period 1972-1987. The increase over time in the age-adjusted incidence of hip fractures in inhabitants 50 years of age and over is the result of changes that act well before the age of 50 years, because the proportional increase in the age specific incidence of these fractures after the age of 50 years did not change over the period studied. The cohort analysis showed that the age-specific incidence of hip fractures in more recently born birth cohorts is higher than that in birth cohorts born long ago. This observation agrees with the other observations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421796 TI - Hip fractures in the elderly: a world-wide projection. AB - Hip fractures are recognized to be a major public health problem in many Western nations, most notably those in North America, Europe and Oceania. Incidence rates for hip fracture in other parts of the world are generally lower than those reported for these predominantly Caucasian populations, and this has led to the belief that osteoporosis represents less of a problem to the nations of Asia, South American and Africa. Demographic changes in the next 60 years, however, will lead to huge increases in the elderly populations of those countries. We have applied available incidence rates for hip fracture from various parts of the world to projected populations in 1990, 2025 and 2050 in order to estimate the numbers of hip fractures which might occur in each of the major continental regions. The projections indicate that the number of hip fractures occurring in the world each year will rise from 1.66 million in 1990 to 6.26 million by 2050. While Europe and North America account for about half of all hip fractures among elderly people today, this proportion will fall to around one quarter in 2050, by which time steep increases will be observed throughout Asia and Latin America. The results suggest that osteoporosis will truly become a global problem over the next half century, and that preventive strategies will be required in parts of the world where they are not currently felt to be necessary. PMID- 1421797 TI - Fracture risk as determined by prospective and retrospective study designs. AB - Both retrospectively and prospectively designed studies consistently show low bone mass and/or bone mineral content (BMC) to be risk factor for low-trauma fractures in postmenopausal women. Along with the reports of such studies there has been concern expressed that BMC measurements overlap between fracture groups, i.e., some women with high BMC develop fractures and some women with low BMC do not. In these commonly used epidemiologic study designs, BMC does not discriminate between those who have and have not experienced the untoward event at some level of the exposure factor. The ability to discriminate is more properly determined by the sensitivity and specificity of the measured value. To contrast the concepts of risk and sensitivity, a nested case-control study was conducted within a 24-year cohort study of women at risk for osteoporosis. We found that for each 1.0 decrement of BMC z-scores, the adjusted relative risk for the prospective study design was 1.67, while the odds ratio obtained from the most recent BMC z-score measurements was 1.87. A receiver operating characteristic (ROC) curve, calculated from the nested case-control study data, showed that BMC z-scores, measured after low-trauma fracture, have both low sensitivity and low specificity to detect existing fracture status. PMID- 1421798 TI - The apparent incidence of hip fracture in Europe: a study of national register sources. AB - The objective of this study was to examine the apparent incidence of hip fracture from discharge rates in European countries. A request was sent to the Ministries of Health in all European countries, asking for the number of hip fracture patients by age and sex, between the years 1983 and 1985. Seventeen countries responded. As expected, hip fracture was most frequently found amongst the elderly, particularly women. The incidence of hip fracture rose exponentially with age in both sexes. It was higher in women than men and there was a three fold range between countries in the female to male sex ratio. There was an eleven fold range in apparent incidence amongst women and a seven-fold range amongst men between the various countries. The highest incidence was found in the northern part of Europe and the lowest in the Mediterranean area. There was a significant positive correlation between the age-standardized incidence rates reported in men from each country and that in women. There was a larger difference in incidence between countries than between sexes, which suggests important genetic or environmental factors in the causation of hip fracture. The extent to which this reflects imperfect capture of data is uncertain but will be important to determine in order to identify reasons for differences and to enable confident projections of the future magnitude of this disorder. PMID- 1421799 TI - Corticosteroid-induced osteoporosis: effects of a treatment with slow-release sodium fluoride. PMID- 1421800 TI - The myth of coupling reagents. AB - Coupling reagents have been proposed for peptide synthesis ever since the introduction of the method because of the convenience of the procedure, which consists of peptide bond formation by addition of a specific condensing agent to the mixture of carboxyl and amine components. However, truly efficient and yet innocuous coupling reagents are hard to find. Most coupling reagents give rise to unwanted reactions, which can be traced to certain characteristic structural features in their molecules. Such features are illustrated with the intermediates generated by dicyclohexylcarbodiimide and N-ethyl-5-phenyl-isoxazolium-3' sulfonate (Woodward's reagent K). Some side reactions can be avoided if peptide bond formation is carried out in two separate steps: activation of the carboxyl group of the carboxyl component in the form of an active ester, followed by the catalyzed aminolysis of the active ester. PMID- 1421801 TI - Synthesis and disulfide structure determination of agelenin: identification of the carboxy-terminus as an amide form. AB - Agelenin, a blocker of the presynaptic calcium channel, is a 35-amino acid peptide having six cysteinyl residues recently isolated from the venom of the spider Agelena opulenta. However, it has not been confirmed whether the carboxy terminus of this peptide is a free acid or amide. To elucidate this, we synthesized both peptides by a solid phase procedure, and compared their elution profiles with that of the natural product on RP-HPLC. The retention time on HPLC as well as the biological activity of the synthetic peptide-amide was found to be identical with those of natural agelenin, confirming that the carboxy-terminus of agelenin is amidated. The disulfide structure of agelenin was also determined to be linked between 3-19, 10-24 and 18-34, by comparing the tryptic peptide linked by two disulfide bonds with those synthesized by the selective formation of disulfide bonds. PMID- 1421802 TI - Incomplete TFA deprotection of N-terminal trityl-asparagine residue in fmoc solid phase peptide chemistry. AB - We demonstrate that TFA deprotection of trityl-protected N-terminal asparagine is incomplete under normal conditions, resulting in low yields or impure products. This phenomenon does not occur if the asparagine is internal, nor for trityl protected N-terminal glutamine. Studies on the deprotection of H Asn(Trt)OH show that the incomplete deprotection is due to the extremely slow removal of a trityl group close to an amino group. The use of the new methyl-trityl protecting group overcomes this problem resulting in rapid and complete deprotection. PMID- 1421803 TI - Bioactive conformation of Arg-Gly-Asp by x-ray data analyses and molecular mechanics. AB - Analysis of well resolved x-ray crystal structure data of proteins (Brookhaven protein data bank) has been combined with molecular mechanics methods using MM2, to determine possible bioactive conformations for the sequence Arg-Gly-Asp, which is believed to be involved in interactions of adhesive proteins with the glycoprotein complexes on activated platelets. In spite of the very flexible nature of this tripeptide fragment, only three general classes of structures were obtained. In one of them, the guanidinium and carboxylate moieties are in hydrogen-bonding proximity, while in the other they are separated by distances of greater than 8 A. Recent literature on the binding affinity of some rigid platelet-aggregation inhibitors seems to support the latter class of structures to correspond to the bioactive conformation. PMID- 1421804 TI - Mercury in a commercial preparation of rat amylin. AB - The biological activity of amylin is reported to vary widely depending on the source and purity of the material. Three commercial samples of rat amylin were compared for structural differences. The samples were nearly identical using most of the available analytical measures--amino acid analysis, HPLC retention, even Edman sequencing data. When the samples were compared by ion spray ionization mass spectrometry, the molecular mass of one sample was 200 daltons higher than anticipated. Careful analysis of the sample, including atomic emission spectrometry, revealed that a mercury atom was associated with the polypeptide. The mercury presumably resulted from a deprotection step in the synthesis, involving the removal of an acetamidomethyl group from cysteine. PMID- 1421805 TI - Identification of a subunit contact site of the alpha-subunit of follitropin. AB - Using synthetic peptides, we previously identified portions of the lutropin alpha subunit that are in contact with the beta-subunit. In order to elucidate structure/function differences of the glycoprotein hormones, a similar study was conducted for follitropin. Peptides corresponding to the follitropin alpha subunit were synthesized using standard solid-phase procedures. Purified peptides were incubated in the presence of alpha- and beta-subunits of follitropin, and subunit recombination was monitored using gel permeation chromatography and reverse-phase high-pressure liquid chromatography. Peptide alpha 33-58, corresponding to a highly conserved portion of alpha-subunit, completely inhibited subunit recombination for 24 h, and allowed only partial (61%-71%) recombination after 48 h. Peptide alpha 51-65 or alpha 61-78 inhibited subunit recombination partially at 24 h, but almost full (greater than 80%) recombination was observed by 48 h. Peptides corresponding to the rest of the alpha-subunit, alpha 1-15, alpha 11-27, alpha 22-39, and alpha 73-92, did not inhibit recombination of the alpha- and beta-subunits. The data suggest that alpha subunits have similar residues in contact with regions of the beta-subunits of both lutropin and follitropin, specifically involving residues from continuous regions of the alpha-subunit (residues 45-75). The data suggest that this region contains multiple sites of contact with the beta-subunit. PMID- 1421806 TI - Automated peptide-resin deprotection/cleavage by a robotic workstation. AB - A robotic workstation has been constructed that automates the deprotection of peptides with trifluoroacetic acid-labile side-chain protecting groups and cleavage from acid-labile resins. The workstation was constructed around a Zymark robot arm and is integrated with a peptide synthesis workstation. Peptide resin samples are deprotected and cleaved with a trifluoroacetic acid/scavenger cocktail that accommodates all common protecting groups used with Fmoc chemistry. Aqueous-ether continuous extraction is used to remove the scavengers and reaction by-products. The apparatus cleaves a 50-500-mg sample of peptide resin every 2 hours and provides the peptides as an aqueous solution in 10% HOAc. Crude peptides obtained with this apparatus are free from residual scavengers and range in yield from 50%-80%. This method is applicable to all but the most hydrophobic peptides and minimizes human contact with the noxious cleavage reagents. PMID- 1421807 TI - Semisynthesis of human growth hormone-releasing factors by alpha-amidating enzyme catalyzed oxidation of glycine-extended precursors. AB - Recombinant alpha-amidating enzyme was used in the semisynthesis (1-5 mg scale) of human growth hormone-releasing factor, GRF(1-44)-NH2, by in vitro enzymatic oxidation of the glycine-extended precursor, GRF(1-44)-Gly-OH, prepared by solid phase synthesis. The equipotent analog, GRF(1-29)-NH2, and the superactive analog, [Ala15]-GRF(1-29)-NH2, were also prepared by this route and were fully characterized. Isolated yields of about 75% were obtained, and the products each possessed full potency in an in vitro rat pituitary bioassay and full receptor binding affinity. Methods to monitor the amidation of polypeptide substrates and analyze the final products are described, including the use of capillary zone electrophoresis. A transient alpha-hydroxyglycine intermediate, [Ala15]-GRF(1-29) Gly(alpha-OH)-OH, was isolated and characterized. Kinetic studies with this intermediate demonstrate that the rat alpha-amidating enzyme from recombinant mouse C127 cells possesses both the monooxygenase and lyase activities needed to catalyze both steps of the amidation process. PMID- 1421808 TI - Potent agonists of growth hormone-releasing hormone. II. AB - Analogs of the 29-amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) or Lys-NH2 in position 29 have been synthesized by the solid phase method, purified, and tested in vitro. Except for one peptide, all analogs contained desaminotyrosine (Dat) in position 1. All contained Nle27 in order to avoid oxidation of Met27. Some peptides contained one or more additional L- or D amino acid substitutions in positions 2, 12, 15, 21, 27 and/or 28. Analogs [Dat1, Ala15, Nle27, Asn28]GH-RH(1-28)Agm (II, [Asn28]-Mz-2-51); [Dat1, Ala15, D-Lys21, Nle27, Asn28]GH-RH(1-28)Agm (III, MZ-3-125); and [Dat1, D-Asn8, Ala15, D-Lys21, Nl27, Asn28]GH-RH(1-28)Agm(IV, MZ-3-129) were 5.7, 2.8, and 3.9 times more potent in vitro, respectively, than GH-RH(1-29)NH2. However, if we compare the potencies of peptides II and III (analogs of the bovine sequence) with those of the analogs of human GH-RH (XII and XIII) [Dat1, Ala15, Nle27]GH-RH(1-28)Agm; [Dat1, Ala15, D Lys21, Nle27]GH-RH(1-28)Agm, respectively, the GH-releasing potency was decreased by 50% and 33%, respectively, by the incorporation of Asn28. Our studies indicate that Lys-NH2 at the C-terminus of GH-RH(1-29) and/or beta-Ala, GABA (gamma aminobutyric acid), and Phe in position 15 are disadvantageous, but potent GH-RH analogs can result from the combination of agmatine in position 29 with other substitutions. PMID- 1421810 TI - Alkylation of tryptophan during deprotection of Tmob-protected carboxamide side chains. AB - Alkylation of tryptophan occurred during the synthesis of a 19-amino acid peptide of the following sequence: Tyr Ala Ala Gln Asn Arg Arg Gly Leu Asp Leu Leu Phe Trp Glu Gln Gly Gly Leu. Alkylation was found to occur during cleavage of the peptide from the solid support under acidic conditions in the presence of Tmob, which is used for protecting glutamine and asparagine. Presence of alkylated tryptophan was confirmed by mass spectrometry, HPLC and amino acid sequence analyses. PMID- 1421809 TI - Synthetic vaccines and HIV-1 hypervariability: a "mixotope" approach. AB - The hypervariability of the gp120 envelope protein principal neutralizing domain, the V3 loop, represents a major problem in the design of vaccines against HIV-1. We have designed a mixed V3 loop peptide, termed "mixotope," obtained in a unique synthesis, and containing around 7.5 x 10(5) different sequences of 22 to 25 residues, organized around the conserved GPGR tetrapeptide. Free or coupled to a carrier protein, the "mixotope" induced in rabbits broadly specific antibodies, which recognized different individual V3 loop sequences, and the native gp120 protein. The "mixotope" approach may allow researchers to focus vaccine strategy against hypervariable functional epitopes of various pathogens. PMID- 1421812 TI - Canine ovulation timing. AB - The key endocrinologic event in the estrous cycle is the luteinizing hormone (LH) peak, which triggers ovulation and thus determines the fertile period. Although LH is impractical to measure directly, a coincidental rise in progesterone also occurs. The recent advent of in-house canine-specific progesterone assays allows accurate identification of the fertile period of the bitch. PMID- 1421811 TI - 4-Methyltrityl (Mtt): a new protecting group for the side chain protection of Asn and Gln in solid-phase peptide synthesis. AB - The trityl group was recently introduced for the protection of the side chain carboxamide function of asparagine and glutamine. The 4-methyltrityl (Mtt) group, a structural modification of trityl, is presented here and allows more rapid cleavage from the protected peptides. Procedures for the introduction of the group and comparative cleavage reactions are also presented. PMID- 1421813 TI - An update of artificial insemination with fresh, chilled, and frozen semen. AB - Two major limitations have been identified in semen extender technology in the dog; the longevity of canine sperm cells is greatly decreased by cooling or freezing, and the anatomy of the canine cervix acts as a barrier to intrauterine deposition of semen via a vaginal insemination. Currently, the ability to predict ovulation time indirectly by measuring serum progesterone levels has increased the success rate using both chilled and frozen canine semen. The American Kennel Club now routinely registers litters produced with both of these methods, and will allow foreign semen from recognized kennel clubs to be imported for domestic use. PMID- 1421814 TI - The use of reproductive hormones in canine reproduction. AB - Naturally produced and synthetically prepared reproductive hormones are frequently employed as pharmaceuticals in canine reproduction. Specific indications for the use of these preparations are few; too often hormonal therapies are used incorrectly and at times deleteriously. Appropriate uses of reproductive hormones are based on known physiological mechanisms in order to improve reproductive efficiency or to treat specific disorders. PMID- 1421815 TI - The role of the veterinarian in genetic counseling. AB - When the veterinarian encounters a disorder with an unknown etiology, the following criteria can identify the potential contribution of the animals genome to the problem: 1. The disorder occurs with higher frequency in a group of related animals than in the general population. 2. A defect involves the same anatomic site in a group of related animals. 3. The disease has a consistent age of onset and clinical course. 4. The disease increases in frequency with inbreeding. 5. The disorder is consistently associated with a specific chromosomal anomaly. 6. The disorder can be traced to an abnormality in a single specific protein molecule. Veterinarians must access the information that knowledgeable breeders gather and channel that information constructively into diagnostic tests, test breedings, and data banks to work toward a common goal- discovery of the genetic basis of disease and development of appropriate breeding programs to minimize or eliminate debilitating genetic problems in dogs. PMID- 1421816 TI - Breeding kennel management. AB - Veterinarians and dog breeders should work together to establish protocols for health care and breeding management that are based on sound scientific principles as well as practical systems. These protocols should involve bitches, stud dogs, and puppies. Tantamount importance must be placed on record keeping so that problems may be identified and solved before they are irreversible. PMID- 1421817 TI - The role of ultrasound in canine reproduction. AB - This article describes the role of ultrasound in the diagnosis of canine pregnancy. Advantages and disadvantages are discussed, and ultrasound is compared with traditional imaging methods. PMID- 1421818 TI - Pregnancy diagnosis by biochemical assay. AB - If pregnancy diagnosis by biochemical assay is to become practical, new marker characterization will be required. Pregnancy marker development is reviewed in dogs and other species, as are molecular biology techniques that have the potential to reveal previously inaccessible targets in the dog. PMID- 1421819 TI - Infertility in the male dog. AB - The diagnosis and characterization of infertility in the male dog depends largely on the initial history and semen evaluation and on following the course of infertility over time. The diagnostic testing described here is helpful for guiding therapy, but the prognosis in serious cases of infertility is usually poor. Cases of subfertility that are not progressive have a better prognosis with optimal breeding management. Finally, the clinician should remember that some insults to the testes are reversible with time so it is important not to administer therapy that will interfere with the dog's ability to recover. Client education is an important part of the management of male dog infertility because it is not uncommon for various drugs to be administered by the breeder, or at the breeder's request, without a sufficient diagnostic work-up. In addition, errors of breeding management may play a role in male dog infertility or limit the success of treatment. PMID- 1421820 TI - Feeding to optimize canine reproductive efficiency. AB - The relationship between nutrition and reproduction is a topic of importance to veterinarians and breeders. Nutrient deficiencies, excesses, and imbalances all are capable of altering reproductive performance. Healthy adult dogs should be fed a diet high in digestibility, low in residue, and high in nutrient bioavailability. Rarely is nutritional intervention necessary during the first half of gestation. During the last half of gestation, switching to a growth/lactation diet and increasing intake by 1.2 to 1.4 x maintenance is indicated. Depending on breed and pup numbers, at peak lactation, feed intake may need to be increased by 2 to 4 x maintenance. The feeding goals of lactation are to minimize loss of bitch body condition score and optimize milk production and pup growth. After weaning, the female who is in poor body condition should remain on a diet rich in protein, fat, and trace nutrients until she is physically/nutritionally repleted. PMID- 1421821 TI - International Symposium on Recombinant Factor VIII (rFVIII) PMID- 1421822 TI - Expression and structure-function properties of recombinant factor VIII. PMID- 1421823 TI - The manufacturing process of recombinant factor VIII, recombinate. AB - In summary, this brief report documents the cell culture and rAHF purification systems used to produce rFVIII and has focused on the unique characteristics of the cell line, the production process, and purification system used. This review emphasizes the general philosophy used throughout the research and development of this innovative and complex therapeutic agent, in order to provide a safe and efficacious rAHF in the management of individuals with hemophilia A. This review provides a brief description of the in-process system and controls that have been incorporated to meet the high standards and safety objective. PMID- 1421825 TI - The manufacturing of the recombinant factor VIII, Kogenate. PMID- 1421824 TI - Current status of clinical studies of recombinant factor VIII (recombinate) in patients with hemophilia A. Recombinate Study Group. PMID- 1421826 TI - Clinical trials of the recombinant factor VIII product, Kogenate. PMID- 1421827 TI - Legal implications of the introduction of recombinant factor VIII. PMID- 1421828 TI - Primary and secondary ethical issues arising from the introduction of recombinant factor VIII: "primum non nocere," but what next? PMID- 1421829 TI - Psychosocial issues surrounding the general or restricted use of recombinant factor VIII: hemophilia clinic perspective. PMID- 1421830 TI - The past and the future: recombinant factor VIII and the consumer. PMID- 1421831 TI - The management of hemophilia patients with inhibitors. PMID- 1421832 TI - [Options for continued development of medical care]. AB - The German health care system is currently faced with challenges that stem from the changing demographic structure of the population as well as from the increasing implementation of costly technological advances in diagnosis and treatment in the presence of inadequate preventive and rehabilitative structures. Ever-rising expectations and demands on the part of German citizens and the increasing number of doctors are threatening to overburden the increasingly limited financial resources of the health care system. The pressure for allocatory measures has led to intense competition amongst the various specialties and sectors of the health care system. In this paper the author describes the current developments with regard to the evolution of the health care system in the near future. He predicts an increasing demand for long-term care facilities especially for the elderly, for more easily accessible rehabilitative services as well as a continuing increasing demand for high-tech services. The pressure of these qualitative as well as quantitative demands in the face of intersectoral competition and limited financial resources will necessarily lead to a restructuring of the professional as well as non professional system with new forms of organization for in-patient as well as out patient services that will address these issues. PMID- 1421833 TI - [Health promotion and wellness programs in private corporate organizations. Problems of trans-national and trans-cultural transferability]. AB - Health promotion and wellness programmes in corporate organisations are subjects of considerable interest to both the providers (companies) and the consumers (employees). Economic considerations constitute a significant factor in businesses' interest in adopting health promotion programmes and in the wellness communities attempts to sell such programming to business. Substantial elements of both the business and wellness communities believe that health promotion programmes are financially profitable in addition to, and as a result of, improving employee's health. A fact which has not yet attracted significant research activities is a comparative analysis of corporate health promotion and wellness programmes in different societies with different cultural backgrounds, corporate cultures and external environments. Especially the emerging of a "New Europe" after the full realisation of the Common Market (EC) after 1992 and the tremendous economic possibilities after substantial political changes in the political structure of the eastern part of Europe (on its way to capitalism) might make it worth to look into corporate wellness programs of European organisations and to discuss pros and cons after comparing them with the ones of their American counterparts. Most important facts in which US organisations differ from most European corporations are not only the internal corporate culture but also the external environment, such as direct government interventions and political pressure from the consumer interest groups (strong unions). In many European countries the government imposes a very tight regulatory and legal framework and dictates the way corporate organisations have to share the burden of health related costs and have to provide occupational, wellness or preventive programmes for their employees.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421834 TI - [The tracer concept of quality assurance in the hospital--a critical evaluation]. AB - The "tracer concept", on which the introduction of quality assurance measures in Germany according to section 137 GRG is based, are critically confronted with the general test philosophy. It is shown that this tracer methodology does not come up to expectations and should be abandoned. Development and introduction of indicators are recommended that would be more appropriate to attain the target of quality assurance: quality improvement. PMID- 1421835 TI - [Organization of social medicine counseling according to section 275 Abs. 4 SGB V exemplified by the Mecklenburg-Vorpommern medical service]. AB - In accordance with social legislation (statute-book of social law, SGB V, section 275, 4) compulsory sickness insurance is obliged to consult the Medical Advisory Service especially in case of general problems of medical supply and advice for patients, quality monitoring, negotiation strategies with all partners of the medical supply system, and for creating joint panels of physicians and sick insurance bodies, particularly examination committees. Exemplarily possibilities of management of these problems are described for the Medical Advisory Service of Mecklenburg-Vorpommern. This example may demonstrate in what way the Medical Advisory Service can bring its own sociomedical competence into play appropriate to regional needs as a service enterprise of the compulsory sickness insurance. PMID- 1421836 TI - [Regional survey of the vaccination rate of 5th grade students exemplified by a rural district in Bavaria]. AB - It was the purpose of this investigation to get a survey of the vaccination rate of eleven-to-twelve-year old pupils in a rural district of Bavaria. We could get the facts by checking the international certificates of vaccination during the medical examination of children in the fifth class of primary schools. The results show that the vaccination rate against polio and tetanus was sufficient, incomplete against diphtheria and insufficient against German measles, mumps and measles. Due to the good cooperation with the primary schools we could get the facts by studying thoroughly 75% of the pupil's certificates of vaccination. A regional survey is a good and inexpensive way of obtaining information on the vaccination rate and it is the last opportunity to achieve a systematic survey of the vaccination rate of children of a certain age. The sero-conversion rate cannot be judged by such a regional survey of the vaccination rate. PMID- 1421837 TI - [The physician's role in relation to the guardianship law]. AB - Legislation concerning guardianship and tutelage of the mentally and/or physically handicapped had so far been governed by the antiquated concept of mental diseases. The revised law (literally: "Care" law) took shape mainly on the lines of the development that followed the great "Psychiatry Inquiry Project" conducted in Germany a few years back. All decisions to be made on the grounds of the new law should always place the well-being of the mentally diseased and handicapped patients first. In this connection medical expertise is one of the most important decision aids for the judge who is called upon to decide on tutelage and guardianship. Hence, demands to be made on the quality of expertises are correspondingly high. PMID- 1421838 TI - Evaluation of solid sorbents for the recovery of polyether toxins (brevetoxins) in seawater. PMID- 1421839 TI - Modification of the method 1 AOAC (CB-method) for the detection of aflatoxins. PMID- 1421840 TI - Modified continuous flow respirometer to measure the effect of tannery effluents on the respiration of earthworms. PMID- 1421841 TI - Monitoring of mutagens in river and marine sediments by Salmonella/microsome assay combined with blue cotton method. PMID- 1421842 TI - Stable blood cell counts after one-week storage at room temperature. PMID- 1421843 TI - Daily intake of metals by females in Osaka, Japan. PMID- 1421844 TI - Formation of cyclohexyl-PCBs upon UV irradiation of PCBs in cyclohexane. PMID- 1421845 TI - Esterase activities during chick embryonic development and its relationship with the metabolism of 2,4-dichlorophenoxyacetic acid butyl ester. PMID- 1421846 TI - Delta-ALAD activity variations in red blood cells in response to lead accumulation in rock doves (Columba livia). PMID- 1421847 TI - Enhanced production of micronuclei by hexavalent chromium in cultured CHO cells. PMID- 1421849 TI - Polycyclic aromatic hydrocarbons in surface waters of Alessandria District, south eastern Piedmont (Italy). PMID- 1421848 TI - Inhibition of implantation caused by methylmercury and mercuric chloride in mouse embryos in vivo. PMID- 1421850 TI - Malathion induced changes in the optomotor behavior of an Indian carp, Labeo rohita. PMID- 1421851 TI - Biotransformation of the flame retardant MC-984 by goldfish, Carassius auratus. PMID- 1421852 TI - Growth pattern changes of Chlorella vulgaris and Anabaena doliolum due to toxicity of dimethoate and endosulfan. PMID- 1421853 TI - Toxicity of kelthane to eyestalk ablated and eyestalk extract injected penaeid prawn, Metapenaeus monoceros (Fabricius). PMID- 1421854 TI - Effects of chromium, copper, nickel, and zinc on survival and feeding of the cladoceran Moina macrocopa. PMID- 1421855 TI - Cadmium induced potassium efflux from Scenedesmus quadricauda. PMID- 1421856 TI - Toxicity of methylmercury to Daphnia pulex. PMID- 1421857 TI - Effect of manganese and iron at a neutral and acidic pH on the hematology of the banded tilapia (Tilapia sparrmanii). PMID- 1421858 TI - Bioaccumulation of yttrium in Pseudomonas fluorescens. PMID- 1421859 TI - Concentrations of aluminum in gut tissue of crayfish (Procambarus clarkii), purged in sodium chloride. PMID- 1421861 TI - Usefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer. AB - In order to decrease the perioperative complications by preoperative cisplatin chemotherapy, the preoperative single administration of cisplatin (30 mg/m2) was performed weekly from one to six times in 36 consecutive patients with esophageal cancer classified as higher than Stage II. The survival curve of 17 patients in Stage III was significantly better (P < 0.05) than that of patients who had been treated without preoperative cisplatin treatment. In 3 of the 12 patients who had locally invasive cancer, either the main tumors or the metastatic lymph nodes, which had invaded the trachea or the left main bronchus, sufficiently receded, so that a curative esophagectomy became possible; 2 of them have survived over 33 months while 1 died of pneumonia 33 months after surgery. The number of perioperative complications was minimal, and thus, we consider that the postoperative use of cisplatin and fluorouracil is indicated in patients in whom a histological response is noted in the resected specimens. PMID- 1421860 TI - Metastatic mode and DNA ploidy in gastric carcinoma. AB - We studied the amounts of nuclear DNA in gastric cancer metastases histologically and cytochemically by flow cytometry, which was performed retrospectively on paraffin-embedded specimens from 95 patients. At surgery, all cases of aneuploid cancer were positive for lymph node metastases. Liver metastases were frequently seen in aneuploid cancer (63%, P < 0.01), while lung metastases were the most common in diploid cancer (50%, P < 0.05). The incidence of peritoneal metastasis was high in undifferentiated diploid cancer (72%, P < 0.01). Local lymph node recurrence after surgery was more common in aneuploid than in diploid cancer (P < 0.01). The incidence of bone and distant lymph node metastasis was found to be strongly dependent on tissue differentiation. The DNA ploidy pattern is thus considered to be closely linked to lymph node, liver, and lung metastases in gastric cancer. PMID- 1421862 TI - Independent clinical and flow cytometric prognostic factors for the survival of patients with stage I gastric cancer. AB - Paraffin-embedded tumor samples from 151 patients with stage I gastric cancer were analyzed by DNA flow cytometry, and 80 patients received an infusion of bromodeoxyuridine (BrdU) to determine S-phase fraction. S-phase fractions of tumors were measured by the immunohistochemical method using anti-BrdU monoclonal antibody. Of the 151 patients, 81 (54%), and 70 (46%) showed diploid and aneuploid patterns. There was no significant association between DNA ploidy and wall invasion, histologic type, or lymphatic invasion. Aneuploid tumors were associated with positive-vessel invasion. When the DNA ploidy and clinicopathological parameters were simultaneously entered into the Cox regression model, DNA ploidy and wall invasion emerged as independent prognostic parameters. Aneuploid tumors had significantly higher values of BrdU labeling indices than diploid ones. These results indicate that the determination of DNA ploidy patterns may be an important prognostic factor in patients with stage I gastric cancer, and may be useful in deciding the therapeutic schedule of patients with gastric cancer. PMID- 1421863 TI - The prognosis of patients with gastric cancer possessing sex hormone receptors. AB - Estrogen receptors (ER) and progesterone receptors (PgR) were immunohistologically investigated in 107 patients with gastric cancer who underwent curative resection. Both ER and PgR were detected only in the cancer cell nucleus. The ER positive rate was 27.7% for males and 31.0% for females, while the PgR positive rate was 9.2% for males and 11.9% for females. Clinicopathologically, the ER positive rate was slightly higher in young females and in cases of poorly differentiated gastric cancer. When cumulative survival rates were analyzed in relation to the presence or absence of receptors, the 10 year cumulative survival rate after surgery was significantly lower in the ER positive cases, being 15.7% cent, than in the ER negative cases, being 62.7%, and also significantly lower in the PgR positive cases, being 18.2%, than in the PgR negative cases, being 48.3%. The coexistence of ER and PgR in gastric cancer tissues suggests that the ER is physiologically active, or that ER positive gastric cancer is hormone-dependent. The poor prognosis of patients with receptor positive gastric cancer suggests that gastric cancer with these receptors is highly malignant. PMID- 1421864 TI - Complete correction of the tetralogy of Fallot in adults using separated extracorporeal circulation to block intrathoracic collateral circulation and improve perfusion of the renal vasculature. AB - During the last 10 years, complete correction of the tetralogy of Fallot (TOF) has been performed on 28 adult patients using the "separated extracorporeal circulation" (separated ECC) technique developed by us. In addition to the usual ascending aortic and dual right arterial cannulations for ECC, the separated ECC also involved femoral arterial cannulation and the insertion of a catheter with two balloons via the other femoral artery. Flow via the ascending aorta and femoral artery were maintained separately during ECC. The urine output during separated ECC was significantly better than that during ordinary ECC (P < 0.01) and the operative field for intracardiac correction was clearer as a result of blocking the collateral circulation. Thus we believe separated ECC to be a superior method for total correction of TOF in adults, which may enhance the operative outcome. PMID- 1421865 TI - An experience of cell sorting using samples isolated from paraffin-embedded tissue of neuroblastoma. AB - Flow cytometric DNA content analyses were performed on samples from 72 patients with neuroblastoma. Nuclear suspensions obtained from paraffin-embedded samples were prepared using the method described by Schutte et al. Determination of DNA ploidy was possible in 62 out of 72 patients. DNA diploidy was detected in 23 (37.1%) and DNA aneuploidy was found in 39 (62.9%) of these 62 patients. Cell sorting was performed on two peak areas of the DNA histogram of samples with aneuploidy. The sorted cells of the first peak area were composed of small round cells and were considered to be normal lymphocytes. The sorted cells of the second peak area were composed of relatively large cells with obvious nucleoli and were considered to be neuroblastoma cells. Thus, two cell components could be distinguished by cell sorting. It is concluded that cell sorting may be of benefit in giving detailed information about DNA histograms, even in samples obtained from paraffin-embedded tissue. PMID- 1421866 TI - Microscopic and immunohistological studies on intimal hyperplasia of the arterially implanted autovein graft and its anastomosis in dogs. AB - The fate of intimal hyperplasia of arterially implanted autovein bypass grafts and their distal end-to-side anastomoses in dogs was studied microscopically and immunohistologically. The bypass grafting was done under conditions of abnormal blood flow and high peripheral resistance. Intimal hyperplasia of the graft first became evident 7 days after implantation and the thickness increased to about 500 microns 3 months or more after the implantation. The intimal hyperplasia was related to an active proliferation of smooth muscle cells which proved positive for alpha-smooth muscle actin staining. Moreover, it was more dominant at the toe and heel of the anastomosis and moderately apparent on the floor of the host artery. The constituent elements of the hyperplastic intima at the anastomosis were fibroblast-like cells and extracellular collagen fibers which were negative for alpha smooth muscle actin staining. This study revealed that the features of intimal hyperplasia at the distal anastomosis in autovein bypass grafting differed from those of the implanted autovein graft itself; the former being related to excessive proliferation of fibroblasts and collagen fibers while the latter displayed an active proliferation of smooth muscle cells. PMID- 1421867 TI - Undifferentiated (embryonal) sarcoma of the liver: report of three cases. AB - Undifferentiated (embryonal) sarcoma is a rare malignant tumor of the liver. It typically presents in late childhood and its prognosis is poor. We experienced three cases of such a tumor during the period of 1976-1989; two of these patients are still alive without disease. Each case was independently treated with a combination of surgery and pre- and/or postoperative chemotherapy, which was found to be effective. In one surviving patient, cyclophosphamide and vincristine were found to be effective, while in the other a combination of cisplatin, Adriamycin (ADM), vincristine and cyclophosphamide was observed to induce a rapid reduction in the size of the recurrent tumor. Thus, an adequate combination of surgery and chemotherapy may improve the prognosis of this tumor. PMID- 1421868 TI - Macronodular adrenal hyperplasia causing Cushing's syndrome: report of two cases and an overview. AB - Of the various entities producing adrenal hyperfunction, nodular adrenal hyperplasia is rarely described, however, recent reports have established it as a distinct cause of Cushing's syndrome. Although the etiology of this disease remains uncertain, two distinct forms are recognised, namely: macronodular hyperplasia and micronodular dysplasia. Establishing the diagnosis preoperatively is difficult but essential to ensure the correct treatment is performed. Two cases of macronodular hyperplasia are reported herein followed by a review of the available literature on this subject. PMID- 1421869 TI - Stercoraceous perforation of the sigmoid colon: report of two cases. AB - Stercoraceous perforation of the sigmoid colon has rarely been reported in the literature. This lesion is assumed to be produced by the pressure from a hard scybalum resulting in a perforated ulcer with necrotic edges. Two cases of stercoraceous perforation of the sigmoid colon are presented in this paper. It is difficult to diagnose this lesion preoperatively, although ultrasonograms proved useful in showing the colon perforation. This lesion should always be suspected when a patient who has had chronic constipation presents with sudden severe abdominal pain. It is possible that this lesion is becoming more common as the mean age of the population increases and we stress the importance of immediate surgery and intensive care for improving the prognosis. PMID- 1421870 TI - Portal vein thrombosis after splenectomy successfully treated by an enormous dosage of fibrinolytic agent in a short period: report of two cases. AB - Portal vein thrombosis (PVT) after splenectomy in a patient with portal hypertension occurs with unusually high frequency. Recently, two patients with PVT following splenectomy were treated by fibrinolytic therapy with an enormous dosage of urokinase (UK) in a short period. PVT was quickly dissolved without side effects and the patients are now doing well without any recurrence of PVT. Therefore, when there is no evidence of bowel infarction, fibrinolytic therapy with an enormous dosage of UK over a short period is deemed to be both effective and essential as a conservative therapy for PVT. PMID- 1421873 TI - Holiday mindfulness. PMID- 1421871 TI - Intussusception of an appendiceal mucocele: report of a case. AB - A 66 year old Japanese female was admitted to our department for the examination and treatment of a mass in the cecum. She had experienced no symptoms or signs other than a positive test result for fecal occult blood. The mass in the cecum was confirmed by barium enema, colonofiberscopy and CT scanning. The presumptive diagnosis was a submucosal tumor of the cecum, however, a laparotomy subsequently revealed intussusception of an appendiceal mass. An ileocaecal resection with an ileocolic anastomosis was therefore performed and the mass was histologically diagnosed as a mucocele of the appendix. This patient is only the 24th case of intussusception of a mucocele of the appendix to be reported in Japan. A review of the available literature on this condition follows the case report. PMID- 1421872 TI - Interferon alpha-2a shows antitumor activity in combination with 5-fluorouracil against human colon carcinoma xenografts: a study in reference to thymidylate synthetase activity inhibition. AB - To clarify the mode of antitumor activity shown by a combination of recombinant human interferon alpha-2a (IFN) and 5-fluorouracil (5-FU), experimental therapy was performed on human colon carcinoma (Co-4) xenografts serially transplanted into nude mice, using IFN and 5-FU, either alone or in combination. IFN alone showed dose-dependent antitumor activity and 5-FU also revealed a moderate antitumor effect. Although IFN, given as 600,000 units/mouse daily sc x 14, and 5 FU, given as 60 mg/kg q4d x 3 ip, showed additive antitumor activity against Co 4, the thymidylate synthetase (TS) inhibition rate was unchanged in the tumors treated with the IFN/5-FU combination in comparison with those treated with 5-FU alone. This suggests that the antitumor activity of IFN and 5-FU in combination does not involve augmentation of the TS inhibition by 5-FU. PMID- 1421874 TI - Role of pulmonary vascular pressure in the first breath: engineering reassessment of Jaykka's experimental findings. PMID- 1421875 TI - Methods of resuscitation in low-Apgar-score newborn infants--a national survey. AB - The incidence, treatment and immediate course in infants with postnatal apnoea were studied. Information on all infants born in Sweden in 1985 with a low Apgar score (3 or less at 1 min or 6 or less at 5 min) was collected from the midwife and from the baby's chart. Of the 97,648 live births, 1633 (1.7%) had a low Apgar score. The risk increased with decreasing birthweight and with severe malformations. Before delivery, 19% of the low-Apgar-score infants were not expected to require resuscitation. Eighty percent of the ventilated infants were satisfactorily ventilated by bag and mask; the remainder were intubated. Of the ventilated infants, 78% developed spontaneous breathing within 10 min after birth and 89% within 20 min. Routine intubation or administration of buffer in cases of postnatal asphyxia had no influence on the time to onset of regular spontaneous breathing. PMID- 1421876 TI - The effect of early and late cord-clamping on blood viscosity and other hemorheological parameters in full-term neonates. AB - This study was done to compare postnatal alterations in blood viscosity (capillary viscometer) and its determinants: hematocrit, plasma viscosity (capillary viscometer), red cell aggregation (Myrenne aggregometer) and red cell deformability (rheoscope) in the first five days of postnatal life in full-term neonates with early (< 10 s) and late (3 min) cord-clamping. The fetal blood volume of the placenta ("residual placental blood volume") decreased from 52 +/- 8 ml/kg of neonatal body weight after early cord-clamping to 15 +/- 4 ml/kg after later cord-clamping. Neonatal blood volume, calculated as the difference between an assumed total feto-placental blood volume of 115 ml/kg and the measured fetal blood volume of the placenta, was 50% higher in the late cord-clamped infants than in the early cord-clamped infants. Both groups showed similar viscosity, hematocrit and other rheological parameters in cord blood. In the infants with early cord-clamping, the hematocrit decreased from 0.48 +/- 0.04 l/l at birth to 0.43 +/- 0.6 l/l after 24 h (p < 0.05). Whole blood viscosity did not change significantly with age. After late cord-clamping, the hematocrit rose from 0.50 +/- 0.04% at birth to 0.63 +/- 0.05 l/l at 2 h of age (p < 0.005) and dropped to 0.59 +/- 0.5 l/l (p < 0.05) at 24 h. Blood viscosity increased by 40% (p < 0.001) within the first 2 h, but did not change significantly during the following five days. In both groups, plasma viscosity and red cell aggregation increased significantly (p < 0.05) on day 5 due to significant increases in total plasma protein and fibrinogen concentrations (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421877 TI - Randomized controlled trial of dexamethasone treatment in very-low-birth-weight infants with ventilator-dependent chronic lung disease. AB - This randomized controlled trial was designed to answer the question: does administration of dexamethasone to neonates with bronchopulmonary dysplasia decrease the need for assisted ventilation? Twenty-five infants with a birth weight < 1501 g, requiring mechanical ventilation and FiO2 of > or = 0.30 at 21 35 days of age, were randomized to treatment with iv dexamethasone or to sham injections for 12 days. The primary outcome criterion was extubation within seven days after study entry. Treatment (n = 12) and control (n = 13) groups were well matched at entry. Dexamethasone facilitated weaning from assisted ventilation (p = 0.0154). There was no increased incidence of infection. Dexamethasone treatment resulted in a significant increase in glucosuria (p = 0.0002) and in systolic blood pressure (p = 0.0034). There was a significant decrease in heart rate (p = 0.0001) and a significant weight loss (p = 0.0002) following dexamethasone treatment. Dexamethasone treatment facilitated weaning from assisted ventilation but several systemic effects were noted that deserve further evaluation before dexamethasone becomes routine treatment. PMID- 1421878 TI - Total leukocyte and neutrophil count changes associated with antenatal betamethasone administration in premature infants. AB - The white blood cell counts of 84 premature infants were included in a retrospective study of 45 infants treated antenatally with betamethasone and 39 non-treated infants. A significant increase in neutrophil and immature neutrophil forms was found in the treated group when the drug was administered to the mother close to delivery. This effect lasted for three days. Afterwards, although the counts were not significantly high compared to the control group, their physiological decrease was delayed. This study indicates that the known stimulating effect of steroids on total leukocyte and neutrophil counts in adult humans and fetal lambs, also occurs in premature infants. This fact supports recent reports which propose the antenatal maternal administration of betamethasone as a cause of leukemoid reaction or leukocytosis after birth. PMID- 1421879 TI - Insensible water loss from the skin during phototherapy in term and preterm infants. AB - The rate of evaporation from the skin was measured before and during phototherapy in 10 full-term and seven preterm infants (gestational age 29-33 weeks). The method for measurement of rate of evaporation was non-invasive and was based on determination of the water vapour pressure gradient close to the skin surface. All infants were studied naked in an incubator with an ambient relative humidity of 50% and with a controlled environment with respect to temperature and air velocity. In the term infants the mean rate of evaporation, measured from an interscapular skin area, was 3.1 g/m2h both before and after 30 min of phototherapy. In the preterm infants the corresponding value was 9.8 g/m2h before and 9.7 g/m2h after 120 min of phototherapy. Thus, in thermally stable infants, non-ionizing radiation from phototherapy equipment does not increase water loss from the skin. PMID- 1421880 TI - Respiratory water loss and oxygen consumption in newborn infants during phototherapy. AB - Respiratory water loss was measured together with oxygen consumption (VO2) and carbon dioxide production (VCO2) in 11 full-term and eight preterm infants (mean gestational age 34 weeks, range 31-36 weeks) before and during 1 h of phototherapy. The method for determination of respiratory water loss, VO2 and VCO2 was based on an open flow-through system with a mass spectrometer for measurement of gas concentrations. All infants were studied naked in an incubator with an ambient relative humidity of 50% and with a controlled environment with respect to temperature and air velocity. The infants were calm during the measurements. Before phototherapy, in term infants respiratory water loss was 4.4 (SD 0.7) mg/kg min and VO2 5.9 (0.9) ml/kg min and in preterm infants respiratory water loss was 4.7 (0.8) mg/kg min and VO2 6.1 (0.8) ml/kg min. No significant difference was found between values obtained during or after 1 h of phototherapy and those obtained before. PMID- 1421881 TI - Lipoproteins in preterm and small-for-gestational-age infants during the first week of life. AB - Plasma lipoprotein levels and composition have been determined in preterm and small-for-gestational-age (SGA) infants, and compared to full-term infants, during the first week of life. Significantly lower levels of HDL and higher levels of VLDL were found in both preterm and SGA infants in comparison to full term healthy infants. These results suggest a low capacity to metabolize VLDL. Preterm infants showed a behaviour similar to full-term infants with regard to the changes in lipoprotein composition. Small-for-gestational-age infants showed a higher lipoprotein lipid content than preterm infants. A low ratio of cholesteryl ester to free cholesterol (CE/FC) was found in both preterm and SGA infants suggesting a reduced lecithin: cholesterol acyl transferase (LCAT) activity. In preterm infants we observed no changes in the CE/FC ratio during the first week of life, whereas in SGA infants this ratio increased after birth. PMID- 1421882 TI - Essential fatty acids in human colostrum. AB - We analyzed the colostrum of 11 mothers, consuming a normal hospital diet, for total fat content and various fatty acids. Three of the mothers had given birth four weeks prematurely. Total fat content of the colostrum ranged from 2.16 to 3.65 g/100 ml. The major fatty acids were palmitic acid (16:0) and oleic acid (18:1) (24.3 and 39.7% (w/w), respectively). The dominating polyunsaturated fatty acid was linoleic acid (18:2n-6) (11.5% of the total fatty acids). Linolenic acid (18:3n-3) and docosahexaenoic acid (22:6n-3) accounted for 0.7 and 0.6%, respectively, of the sum of total fatty acids. The ratio of polyunsaturated to saturated fatty acids was 0.42, ranging from 0.28 to 0.5, and the ratio of n-6/n 3 fatty acids was 6:1. Linoleic acid and linolenic acid were positively correlated with each other (p < 0.02), whereas palmitic acid was negatively correlated with oleic acid (p < 0.05). We conclude that the average human colostrum contains the recommended level and balance of the essential fatty acids required by the newborn baby. PMID- 1421883 TI - Transient colonization of the gut of newborn infants by orally administered bifidobacteria and lactobacilli. AB - We investigated if orally administered bifidobacteria and/or lactobacilli could be cultured from faeces of infants after antibiotic treatment, when these bacterial species are usually absent. Lyophilized Bifidobacterium longum, strain BB-536, B. breve, strain BB-576, or Lactobacillus acidophilus, strain LAC-343, were used. Doses of 3 x 10(9) cells of one strain, or a mixture of all three strains 3 x 10(9) cells each were fed three times daily at mealtimes to 11 infants aged 0-8 weeks. Treatment was started the first day after antibiotic treatment and was continued for 5 days. The bacterial species were isolated in 9 of 11, 7 of 10 and 2 of 9 specimens obtained on the last day of bifidobacteria or lactobacilli administration, 5 and 15 days thereafter, respectively. No side effects were noted. PMID- 1421884 TI - Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture. AB - We observed 12 very preterm infants (10 males) with a peculiar respiratory syndrome characterized by early onset soon after birth and by a biphasic course. The severe first phase was characterized by a clinical pattern mimicking the idiopathic respiratory distress syndrome of prematurity. Gradually, respiratory symptoms decreased and assisted ventilation with oxygen therapy was reduced. In the second phase, a significant worsening of respiratory signs and the appearance of apneic spells were observed. Chest X-ray showed hypoexpansion of the lungs and the prevalence of a fine reticular pattern. Chlamydia trachomatis was identified in this second phase in conjunctival and pharyngeal swabs and/or on tracheal aspirates. Our data suggest that in the very preterm infants, chlamydial infection shows different clinical and laboratory features if compared with Chlamydia trachomatis pneumonia of infants born at term. PMID- 1421885 TI - Transfer of specific IgG and IgG subclasses to herpes simplex virus across the blood-brain barrier and placenta in preterm and term newborns. AB - The kinetics of virus-specific IgG subclasses (IgG 1-4) among newborns and their mothers has not yet been determined. In this report, we examined anti-herpes simplex virus IgG activities (HSV-IgG) and its subclasses in CSF and serum of premature or term newborns without HSV infection and in the serum of their mothers using ELISA. We found that CSF/serum ratios of HSV-IgG and IgG subclasses (IgG 1-4) in newborns with a gestational age less than 38 weeks were higher than those of term newborns. These findings indicate that the blood-brain barrier against HSV-IgG and IgG subclasses is insufficient in newborns. Furthermore, we found that HSV-IgG subclasses, which were transferred across the placenta and later transferred across the blood-brain barrier had a tendency to be proportional to each of the maternal HSV-IgG subclasses. PMID- 1421886 TI - Neurological adaptation of infants delivered by emergency or elective cesarean section. AB - The effects of intrapartal asphyxia on neonatal neurological condition have been studied in 17 full-term infants delivered by emergency cesarean section and in 30 full-term infants delivered by elective cesarean section used as controls. A neurological examination consisting of 31 items was performed on days 1, 2 and 5 after birth. A tonus score, an excitability score as well as the number of optimal responses were calculated. A follow-up examination was done at six months of age with a standardized neurological and developmental examination. The results showed that infants born after emergency cesarean section were significantly more hypotone the first two days after delivery than the infants in the elective cesarean section group. In regard to individual neurological items, significant differences were found between the emergency and elective cesarean section in reaction to sound, rooting, patellar, Moro and stepping reflexes with weaker reactions in the elective cesarean section group. Growth, psychomotor development and neurological status at six months did not differ significantly between the groups. Our findings indicate that full-term infants born after emergency cesarean section due to mild intrapartal asphyxia have a delayed neurological adaptation as expressed by poor muscular tonus during their first days of life compared with infants born after elective cesarean section. PMID- 1421887 TI - Hyperbilirubinemia, hypocarbia and periventricular leukomalacia in preterm infants: relationship to cerebral palsy. AB - This study comprised 103 preterm infants with a gestational age less than 33 weeks who were born in Tampere University Hospital and who were followed up to two years of age. Sixty-four perinatal variables were compared to ultrasound findings in the neonatal period and neurologic handicap at the age of two years. Duration of hypocarbia (PCO2 < or = 30 mmHg) during the first 72 h and hyperbilirubinemia (the mean level of serum total bilirubin) at three days of age were independently and significantly related to periventricular leukomalacia, but not directly to cerebral palsy. The only perinatal variables related independently and significantly to cerebral palsy at two years of age were periventricular leukomalacia and ventriculomegaly. According to these results, periventricular leukomalacia was the main predictor of cerebral palsy in preterm infants. In addition to hypocarbia, hyperbilirubinemia may also be involved in the pathogenesis of extensive (severe cystic) periventricular leukomalacia. PMID- 1421888 TI - Comparison between tape-recorded and amplitude-integrated EEG monitoring in sick newborn infants. AB - In 15 ill newborn infants a comparison between long-term multichannel and single channel recordings of simultaneously tape-recorded (Medilog system) and amplitude integrated EEG (Cerebral Function Monitor) was made. There was good agreement between the main type of background activity diagnosed with the tape-recorded and the amplitude-integrated EEG for all recordings. Two infants had repetitive subclinical and subtle seizure activity, lasting for several hours, which was detected by both techniques. Short, single seizures were diagnosed in the recordings of nine infants. When a single electrographic seizure appeared in an otherwise stable recording, it was identified by both the tape-recorded and the amplitude-integrated EEG. Very short (5-30 s) seizure patterns, which were diagnosed with the tape-recorded EEG, were not identified in the cerebral function monitor recordings. In the single-channel recordings of both the EEG and the cerebral function monitor there were, on some occasions, difficulties in distinguishing single seizures from interference due to external artefacts. In the multichannel recordings the diagnosis of seizure patterns was facilitated by comparison with the other channels. Both the Medilog EEG and the cerebral function monitor are feasible techniques for following cerebral electrical activity in sick neonates, although neither technique is specifically constructed for this purpose. For clinical use in the neonatal intensive care unit the advantage with the cerebral function monitor is the immediately available recording. The tape-recorded EEG offers possibilities of more channels and a higher reliability when diagnosing short subclinical seizures, however, only after offline analysis. PMID- 1421889 TI - Sister chromatid exchanges in peripheral lymphocytes in newborns treated with phototherapy and vitamin E. AB - A study was undertaken to determine whether blue fluorescent light might affect the sister chromatid exchange (SCE) frequency of peripheral lymphocytes in icteric newborns undergoing continuous phototherapy treatment (72 h). Also, the potential preventive effect of vitamin E on SCE frequency was studied in a subgroup of 11 preterm and 9 fullterm newborns after daily administration of vitamin E (46.44 mumol/kg/d, im). The results revealed that only the preterm icteric newborns showed an increase in mean SCE frequency of peripheral lymphocytes after phototherapy (9%, p = 0.02), but in no case did the highest SCEs/cell ratio exceed the normal values. No correlation was found between the average SCE rate and birth weight, gestational age or bilirubin levels. Also, no difference in SCEs was observed between newborns treated or untreated with vitamin E. PMID- 1421890 TI - Iron status in low-birth-weight infants, small and appropriate for gestational age. A follow-up study. AB - Iron nutrition was measured in 84 low-birth-weight infants. At birth, they were assigned to three groups: preterm infants appropriate for gestational age (n = 29); preterm infants small for gestational age (n = 17); and full-term infants small for gestational age (n = 38). A sub-sample of infants was supplemented with iron 3 mg/kg from two to four months of age. At birth, preterm appropriate-for gestational-age infants had a lower hemoglobin concentration than full-term small for-gestational-age infants (p < 0.01) and a higher serum ferritin than preterm small-for-gestational-age infants (p < 0.05). In the non-supplemented group, full term small-for-gestational-age infants had significantly higher hemoglobin concentrations at four months of age. At this age, iron-supplemented preterm infants appropriate or small for gestational age had significantly higher hemoglobin levels than non-supplemented subjects, while iron supplementation did not have an effect on final hemoglobin concentration in full-term small-for gestational-age infants. We conclude that preterm infants, irrespective of their adequacy for gestational age, show evidence of iron deficiency before four months of age. Full-term infants do not develop iron deficiency up to this age. PMID- 1421891 TI - Relationship between neonatal behavior and subsequent temperament. AB - The validity of the neonatal behavioral assessment scale in predicting later infant temperament is of theoretical and clinical importance. The scale was administered to 47 full-term healthy neonates. Of these, 40 were followed and the infant characteristics questionnaire was given at four months of age. Significant correlations were revealed between the neonatal assessment items from the clusters of orientation and motor maturity and the temperament factors "fussy difficult" and "unpredictable". Items from the cluster of autonomic stability correlated with the temperament factor "unadaptable." These correlations possibly indicate that perceived temperament does reflect intrinsic infant qualities. PMID- 1421892 TI - Persistence of respiratory symptoms into the second year of life: predictive factors in infants born preterm. AB - Preterm infants frequently suffer from recurrent respiratory symptoms in the first year of life. Our aims were to assess if such respiratory morbidity persisted beyond the first year and to define the predictive factors. One hundred and seventeen infants (median gestational age 29 weeks) were followed prospectively for two years. Thirty-eight infants had symptoms only in the first year (group A) and in a further 20 infants, symptoms were present in both years (group B). Comparison of these two groups revealed no significant difference in birth weight or gestational age, but the duration of ventilation and increased inspired oxygen concentration were significantly longer in group B. Significantly more infants in group B had had an air leak in the neonatal period, and airways resistance at six months of age was also significantly higher in group B. We conclude that infants with severe neonatal respiratory distress are likely to have persisting respiratory morbidity and that respiratory function measurements at six months of age provide the most accurate predictor of chronic respiratory symptoms. PMID- 1421893 TI - Gestational age correction for height in preterm children to seven years of age. AB - Correction for gestational age continues to make a difference to the height SD score (SDS) to the age of seven years in very preterm babies. The height SDS for children born at 28 weeks' gestation increased by 0.25 SDS when postconceptual age was used instead of real age. Extrapolating from these results, the effect of correction would be an increase of approximately 0.32 SDS for a seven-year-old of 24 weeks' gestation. Unsatisfactory growth may be masked by a steady or increasing real age SDS in a few children. The risks of stopping using postconceptual age at two or three years include both false confidence in genuine cases of growth retardation and misinterpretation of a decrease in height SDS as evidence of growth retardation. As the number of very preterm babies who survive increases so does the importance of these observations. PMID- 1421894 TI - High noise levels in infant incubators can be reduced. PMID- 1421895 TI - CSF ascorbic acid and lactate levels after neonatal asphyxia: preliminary results. PMID- 1421896 TI - Early hyponatraemia and neonatal drug withdrawal. PMID- 1421897 TI - Neonatal pericarditis as a presenting manifestation of chronic granulomatous disease. PMID- 1421898 TI - Hydrops fetalis associated with Ureaplasma urealyticum. AB - A hydroptic newborn was born at 32 weeks' gestation and at the age of 14 h died of post-asphyxial syndrome. Immunologic causes of hydrops fetalis were excluded, as were anomalies and chromosomal aberrations. Ureaplasma urealyticum was isolated in bronchial secretions, lung tissue and brain tissue of the newborn. Our findings suggest that U. urealyticum infection should be considered in the differential diagnosis of hydrops fetalis. PMID- 1421899 TI - A case of familial nesidioblastosis: prenatal diagnosis of foetal hyperinsulinism. AB - Persistent neonatal hyperinsulinaemic hypoglycaemia due to nesidioblastosis is a rare condition probably transmitted by an autosomal recessive inheritance. Recurrent hypoglycaemic episodes become evident after birth and cause severe neurological damage without intensive treatment. The intrauterine detection of hypoglycaemia and hyperinsulinism in newborns subsequently diagnosed as affected by nesidioblastosis has not yet been reported. We describe a case of familial nesidioblastosis in which an intrauterine diagnosis could be suggested by high levels of insulin and C-peptide and low values of glucose in the amniotic fluid. PMID- 1421900 TI - Neonatal Salmonella panama infection with meningitis. AB - Three full-term neonates contracted a hospital infection with Salmonella panama derived from the mother of one. Two had bacteraemia and meningitis; one developed a brain abscess and the other recurrent meningitis at two months. The third neonate had gastroenteritis only. Six months later they had developed normally and two were still excreting salmonellae in the stools. PMID- 1421901 TI - Vitamin K prophylaxis and vitamin K deficiency bleeding (VKDB) in early infancy. AB - The efficacy of vitamin K prophylaxis (1 mg im or sc, or 1-2 mg orally both given as a single dose at birth) in the prevention of vitamin K deficiency bleeding in early infancy was estimated in Germany during a 15-month period between 1988 and 1989. Cases were identified by a survey of all paediatric hospitals and population denominators by a survey of all obstetric hospitals. Response rates were 85% and 68%, respectively. Thirteen cases of vitamin K deficiency bleeding in early infancy with confirmed prophylactic states were confirmed, seven of whom had intracranial haemorrhage. The estimated efficacy of single parenteral administration of vitamin K versus no prophylaxis was 96.7% (95% confidence interval: 74-99.6%) and for single oral administration versus no prophylaxis 80.4% (9.1-95.6%). Single parenteral vitamin K prophylaxis gave substantial protection against vitamin K deficiency bleeding in early infancy. Single oral prophylaxis appeared to be less effective, although the difference was not significant, as indicated by the wide overlap of the respective 95% confidence intervals. PMID- 1421902 TI - Vitamin K status in cystic fibrosis. AB - Appearance of PIVKA-II (protein induced by vitamin K absence-II) in serum is a biochemical sign of insufficient vitamin K-dependent carboxylation of prothrombin. Plasma concentrations of PIVKA-II and vitamin K1 were determined in 24 children with cystic fibrosis. Eight were supplemented with vitamin K1. The purpose of the study was to determine the occurrence of vitamin K deficiency in cystic fibrosis and to evaluate the effect of vitamin K supplementation. PIVKA-II was detectable in only one unsupplemented child. In this patient, the concentration of vitamin K1 was below the limit of detection of 60 ng/l. Vitamin K1 levels in the other unsupplemented children were normal (mean 476 ng/l = 1 mmol/l). The supplemented patients showed extremely high levels of vitamin K1 (mean 22445 ng/l = 50 nmol/l). In conclusion, vitamin K deficiency occurs infrequently in cystic fibrosis. Checking the coagulation system is advised, but routine vitamin K supplementation is not recommended. If additional vitamin K is needed, the starting dose should not exceed 1 mg daily. PMID- 1421903 TI - Neonatal polycythemia in appropriately grown infants of hypertensive mothers. AB - Neonatal polycythemia is a frequent finding after pregnancies complicated by diabetes and by maternal hypertension with intrauterine growth retardation (IUGR). It is still unclear if the association of polycythemia with hypertension is the result of IUGR or of hypertension per se. To establish the incidence of neonatal polycythemia in populations at risk, we analyzed the results of hematocrit values obtained from 1592 neonates born consecutively at the Hospital de Clinicas, Buenos Aires. Capillary hematocrit values were obtained by heel stick before 6 h of age. When the values were 65% or greater, new samples were obtained from an antecubital vein. The risk of polycythemia in appropriately grown infants of hypertensive mothers was 12.6-fold greater than the risk in the general population. These data show that maternal hypertension poses a significant risk for polycythemia, regardless of fetal growth. We suggest that, to prevent possible sequela, hematocrit is measured routinely in all infants of hypertensive mothers for prompt diagnosis and treatment. PMID- 1421905 TI - Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus. AB - The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated. PMID- 1421904 TI - Exogenous porcine surfactant (Curosurf) is inactivated by monoclonal antibody to the surfactant-associated hydrophobic protein SP-B. AB - A monoclonal antibody to the surfactant-associated hydrophobic protein SP-B was added at various concentrations to a standard preparation of porcine surfactant (Curosurf 10 mg/ml), and surface properties were evaluated with pulsating bubble. Retarded adsorption of surfactant was observed at antibody concentrations > or = 0.5 mg/ml and significantly increased values for minimum surface tension were observed at antibody concentrations > or = 1 mg/ml. In vivo effects of the antibody were tested in immature newborn rabbits ventilated with a standardized sequence of insufflation pressures. Animals receiving 0.1 ml surfactant (80 mg/ml) mixed with antibody at concentrations > or = 4 mg/ml had low tidal volumes, poor lung stability in pressure-volume recordings, poor alveolar expansion in histological sections and widespread epithelial necrosis in peripheral airways. Admixtures of IgG had no such effects. We conclude that this monoclonal antibody inactivates exogenous porcine surfactant, probably by preventing fast adsorption of surfactant lipids to the alveolar air-liquid interfaces. PMID- 1421906 TI - Circulating levels of endothelin and atrial natriuretic factor during postnatal life. AB - We determined plasma endothelin-1-like immunoreactivity and atrial natriuretic factor concentrations in preterm and full-term newborn infants during the first month of life. Plasma endothelin-1-like immunoreactivity levels were far greater than those of maternal blood in the newborn infants. The highest plasma endothelin-1-like immunoreactivity levels were observed on the first day of life (8.7 +/- 3.7 pmol/l) and gradually decreased with age. There was no significant difference in plasma endothelin-1-like immunoreactivity levels between preterm and full-term infants. A good correlation was observed between plasma endothelin 1-like immunoreactivity levels and atrial natriuretic factor concentrations (p < 0.01). These results suggest that circulating endothelin may regulate the cardiovascular system in the newborn period. PMID- 1421907 TI - Rapid decrease in tuberculin skin test reactivity at preschool age after newborn vaccination. AB - A study of tuberculin sensitivity was performed in 353 children aged 4-6 years, all vaccinated at birth with British BCG vaccine. Significant waning of tuberculin reactions with increasing age was found (p < 0.05). In the age group < 4.5 years, the mean tuberculin reaction was 6.6 mm, in the age group 4.5-5.5 years 5.2 mm and in the age group of > 5.5 years 3.5 mm. The number of children with positive reactions (> or = 5 mm) was 165 (40%) and those with strong reactions (> or = 10 mm) 49 (14%). None of the latter children had active tuberculosis during a follow-up period of 12 months. Eighty-three (24%) of the children had no reaction. The children who had been revaccinated with the MPR vaccine against measles, rubella and parotitis (n = 31) had significantly larger tuberculin reactions than the non-revaccinated children. Atopic dermatitis or infections during the preceding six months did not have any significant influence on reaction sizes. Our results demonstrate that the variation in size of tuberculin reactions after BCG vaccination at birth is large. We conclude that tuberculin sensitivity wanes rapidly by the age of 4.0-6.3 years. PMID- 1421908 TI - Treatment of hypercholesterolemia in children and adolescents. AB - In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421909 TI - Growth and nutrition in 10 girls with Rett syndrome. AB - Cross-sectional and retrospective data on growth and anthropometric outcome, feeding problems and dietary intake are presented for 10 girls between three and 16 years of age with Rett syndrome. All girls had birth weight and length within the normal range for gestational age and development was considered normal until six to 24 months of age. The girls presented a fall off in linear growth during the first two years of life and at the time of study, all but one had height and/or weight for height below the 2.5th percentile of healthy children. The girls had good appetite but could not eat by themselves and oral-motor dysfunctions were common. The mean energy intake was 66.9% of the US recommendations according to age and 107.8% of the recommendations according to body weight. The intakes of thiamin, vitamin D, calcium and iron were considered low. None was anaemic. Different nutritional intervention strategies should be investigated to reduce and, if possible, prevent malnutrition and wasting in girls with Rett syndrome. PMID- 1421910 TI - Does growth hormone treatment of patients with Turner's syndrome cause an abnormal body shape? AB - The effect of human growth hormone on the body shape of 51 patients with Turner's syndrome (aged 6-19 years) was evaluated. Biosynthetic growth hormone was given in a dose of 24 IU/m2 body surface/week for two years. Karyotype analysis on peripheral blood was performed. Patients older than 12 years also received 0.1 microgram ethinyl oestradiol/kg body weight/day orally. Body shape was characterized by studying pairs of measurements expressed as SD scores (z scores). As reference data, our own locally obtained data from normal children were used. After two years of growth hormone therapy, height, sitting height, bi acromial and bi-iliac diameter increased from -3.7, -2.9, -1.7 and -1.2 to -1.3, 2.5, -0.6 and +0.5 z scores, respectively. The shape of the patients, expressed as height/bi-iliac diameter and also as sitting height/bi-iliac diameter became more abnormal. As no difference could be noted between the prepubertal and pubertal groups or between the XO and mosaic groups, it is suggested that growth hormone treatment causes a relatively wide pelvis in patients with Turner's syndrome. PMID- 1421912 TI - Selective growth hormone deficiency of hypothalamic origin following severe head injury. PMID- 1421911 TI - Single daily doses of trimethoprim/sulphadiazine for three or 10 days in urinary tract infections. AB - We conducted a prospective randomized study to evaluate the efficacy of a single daily dose of 4 mg/kg of trimethoprim coupled with 17.5 mg/kg of sulphadiazine for three (group 1) or 10 days (group 2) in the treatment of uncomplicated urinary tract infections in children. Forty patients (nine boys and 31 girls) aged 2.5-18 years, presenting with a urinary tract infection were allocated to one of the two groups. Patients were seen three, 10, and > or = 38 days after the initiation of treatment. Control urine cultures were negative in all patients at days 3 and 10. Two patients in group 1 and one patient in group 2 suffered a relapse within a month. Single doses of trimethoprim/sulphadiazine for three or 10 days are effective in the treatment of uncomplicated urinary tract infections in children. PMID- 1421913 TI - Zinc, copper and iron in serum and hair of newborns and their correlation with clinical data. PMID- 1421914 TI - Echo-Doppler abnormalities in mucopolysaccharide storage diseases. PMID- 1421915 TI - Acute renal failure in a neonate due to pelviureteric candidal bezoars successfully treated with long-term systemic fluconazole. AB - Systemic candidiasis with renal involvement is a rare but well-recognized complication during intensive care treatment in very-low-birth-weight infants. We report a term neonate who developed anuria associated with bilateral bezoar formation in the renal pelvis and candidemia. The treatment consisted of placement of a nephrostomy tube in the left kidney, short-term irrigation with amphotericin B and iv, and later, oral administration of fluconazole. PMID- 1421916 TI - Intracardiac rhabdomyomas in neonates: report of three cases. AB - Three cases of intracardiac rhabdomyomas in neonates are presented. All were diagnosed by ultrasound, one prenatally and two directly after birth. Two of the patients were operated on during the neonatal period. The operations were carried out on the ultrasound findings alone. One patient was considered inoperable and died at three weeks of age. The two surviving patients have no cardiac symptoms and involution of the tumors has taken place. Two of the three patients have shown signs of tuberous sclerosis. PMID- 1421917 TI - Anesthesia-induced rhabdomyolysis in infants with unsuspected Duchenne dystrophy. AB - Anesthesia-induced rhabdomyolysis in infancy may represent an unsuspected Duchenne dystrophy. In order to establish the diagnosis of this genetic disease more definitively, a dystrophin test is a requisite following the conventional creatine kinase test and light and electron microscopies of the muscle biopsy. PMID- 1421918 TI - Noma neonatorum: an unusual case of noma involving a full-term neonate. AB - Noma neonatorum is a gangrenous process that occurs in the oral, nasal or anal area and occasionally the eyelids and scrotum of the newborn. The disease is caused by Pseudomonas aeruginosa and usually affects premature ill babies during the first few weeks of life. A full-term neonate with nasal and scrotal noma is uncommon and is therefore reported. PMID- 1421919 TI - Shoshin beriberi in an infant of a thiamine-deficient mother. AB - The classical form of thiamine deficiency in children is comprised of peripheral neuropathy, encephalopathy and high-output cardiac failure, predominantly right sided. "Shoshin beriberi" cardiac failure has a different presentation, with vasoconstriction, hypotension and severe metabolic acidosis. A three-month breast fed infant developed these features (biochemical tests confirmed the diagnosis). His mother, although non-symptomatic, had biochemical evidence of thiamine deficiency. PMID- 1421920 TI - Miliary tuberculosis with acute respiratory failure and histiocytic hemophagocytosis. Successful treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213. AB - A 14-year-old girl with high fever, dyspnea and bilateral miliary nodules on chest X-ray, developed a rapidly progressive respiratory failure associated with histiocytic hemophagocytosis. Histologic examination of bone marrow biopsy revealed tuberculous granulomas with caseating necrosis. We report a pediatric case in which treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213 was successful. PMID- 1421921 TI - Late hemorrhagic disease of newborn: a case with increased vitamin K requirement. PMID- 1421922 TI - Erythema multiforme as a single manifestation of cow's milk intolerance. PMID- 1421923 TI - Role of cereal-based oral rehydration therapy in persistent diarrhoea in children. AB - A total of 2000 children aged under five and 12,500 diarrhoea episodes were studied prospectively for assessing the efficacies of R-ORS and G-ORS and for comparing them with that of a comparison area using drugs for treatment. Efficacy was evaluated in terms of ORS use rate, consumption of ORS per episode, duration of diarrhoea and rate of recovery. The data were analysed to compare the rate of persistent diarrhoea in the three areas. Mean ORS consumption was 946 +/- 576 and 1236 +/- 766 ml per episode of watery diarrhoea in the R-ORS and G-ORS areas respectively. The mean durations of watery diarrhoea were 3.3 +/- 2.1, 5.4 +/- 3.5 and 8.8 +/- 5.5 days in the R-ORS, G-ORS and comparison area, respectively. The median durations for dysentery were 7, 9 and 12 days in the three areas respectively. The incidences of persistent diarrhoea following water diarrhoea were 0.4, 3 and 12% in the R-ORS, G-ORS and comparison area respectively, and, following dysenteric episodes, 8, 18 and 40%. The results of the study suggest that R-ORS can hasten recovery from both watery diarrhoea and dysenteries, thus reducing the incidence of persistent diarrhoea. PMID- 1421924 TI - Is small bowel bacterial overgrowth of pathogenic significance in persistent diarrhea? AB - Bacterial overgrowth in the upper small intestine is postulated to cause persistent diarrhea. We compared the fecal and upper intestinal flora in 82 patients with persistent diarrhea aged < or = 36 months and weight-for-length < or = 90% of National Center for Health Statistics standards (NCHS) and 39 non diarrheal children with age < or = 36 months, nutritionally matched with the patients and residing in the same environment. In the age groups < or = 12 months and > 12 months the duodenal fluid bacterial counts > or = 10(5)/ml were found with similar frequency in patients and controls for aerobic (p = 0.33; p = 0.1) and anaerobic (p = 1.0; p = 1.0) bacteria. However, the duodenal isolation rates of any aerobic bacteria (p < 0.05) without regard to counts and Enterobacteriaceae (p = 0.06) were higher in patients than in controls. Colonization with Enterobacteriaceae was directly correlated with increased stool weight over a 7-day observation period (p < 0.05; p < 0.01). One or more pathogens were isolated in the feces of 58% of the patients and 43.8% of the controls. Enteroadherent E. coli of the localized [EAEC-L] (p < 0.01) and aggregative [EAggEC] (p = 0.22) phenotypes were isolated more commonly from the feces of patients. The duodenal fluid detection rates for Klebsiella were significantly greater (p < 0.01) in patients, while Giardia lamblia was detected more commonly in the duodenal fluid of controls (p < 0.01). The presence of specific pathogens in the feces did not seem to be related to the extent of small bowel colonization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421925 TI - The role of the duodenal microflora as a determinant of persistent diarrhoea. AB - It has been suggested that proliferation of enterobacteriaceae and/or anaerobes in the duodenum of some children with acute diarrhoea determines whether the episode becomes persistent. A review of published studies and the comparison of cultures of duodenal aspirates from Peruvian children with acute and persistent diarrhoea and diarrhoea-free children did not support this hypothesis. Although many children had enterobacteriaceae and/or anaerobes cultured there was no correlation with clinical and nutritional outcome. Age, nutritional status, the environment and the aetiology of the episode were determinants of the duodenal microflora independent of diarrhoea. Culture of the duodenal aspirates did not increase the yield of enteropathogens which were isolated more frequently from stools than from the duodenum. Despite the presence of a single strain or serotype of enterobacteriaceae suggesting that these bacteria were colonizing the duodenum, we were unable to demonstrate any adherence mechanisms in the majority of them. Two of ten bacteria with no other evidence of virulence caused diarrhoea in the RITARD rabbit model. PMID- 1421926 TI - Persistent diarrhea as a cause of childhood mortality in rural Bangladesh. AB - To determine the importance of persistent diarrhea in childhood mortality a multiple-step verbal autopsy method was used to study 1934 deaths in Matlab, Bangladesh. We found that most of the deaths from acute watery diarrhea occurred in infancy, whereas the peak of non-watery diarrhea deaths was in children over 12 months of age. Children suffering from persistent diarrhea and malnutrition were at highest risk of dying during their third year of life. Children with infectious diseases have a two to four times higher risk of dying if they are malnourished, and for diarrhea the risk is 17 times as high. Forty-nine percent of the diarrheal deaths were in children with malnutrition associated with persistent diarrhea. These results imply that fluid and dietary management are key aspects in the treatment of diarrhea, particularly for those episodes which persist. We conclude that attempts to reduce diarrhoeal deaths with vertical ORT programmes will not have major impact unless other interventions are directed to the persistent diarrhoea-malnutrition complex. PMID- 1421927 TI - Clinical aspects of acute vs persistent diarrhea in Ho Chi Minh City, Vietnam. AB - A retrospective clinical study of acute and persistent diarrhea in children younger than three years of age was conducted for 12 months (October 1989 to September 1990) in a Pediatric Hospital in Ho Chi Minh City, South Vietnam. Most of the 3833 episodes of diarrhea identified were of short duration, with 77.7% lasting only 1-7 days. Only 5.3% of episodes lasted more than 14 days. Episodes of longer duration were associated with young age (0-5 months). Bloody stool was present in more than 40% of persistent episodes. Severe malnutrition was associated with persistent episodes that lasted 14-21 days (33%) or more than 22 days (59%). It is important that all patients with diarrhea have appropriate dietary management in addition to fluid therapy, and that future analysis examines etiologic factors to determine the optimal treatment of bloody diarrhea. PMID- 1421928 TI - Persistent diarrhea in Vietnamese children: a preliminary report. AB - The clinical and laboratory features of persistent diarrhea were investigated in 83 children under three years of age who were treated in the Gastroenterology Division of the Institute for the Protection of Children's Health, Hanoi from August 1988 to August 1989. The number of cases of diarrhea was highest in the children aged 4-5 months. The mean age of the children studied was 6.6 +/- 3.4 months. The ratio of males to females was 2.6 and mean age of first episode of diarrhea was 4.3 +/- 3.4 months; persistent diarrhea was more common in children under six months of age than in older children. Persistent diarrhea occurred in the first diarrheal episode in 66.5% of cases. Recent nonenteric infections were found in 30% of the study group. Of the 83 children studied, 36% had stool specimens positive for enteric pathogens; 24% had enterotoxigenic Escherichia coli isolated, 8% had enteropathogenic E. coli, 5% rotavirus, 6% Candida, and 4% Giardia lamblia. The duration of diarrhea was longer in children who received antibiotics than in those who did not (p < 0.01). PMID- 1421929 TI - Determinants of dietary intake during childhood diarrhea and implications for appropriate nutritional therapy. AB - Diarrheal diseases have a well recognized negative effect on children's growth, probably due in part to reduced dietary intake during illness. Previous studies have shown that the effects of diarrhea on dietary intake are greater among hospitalized children than among those observed in their homes. Breast milk intake does not change during diarrhea, however, so breast-fed children are less likely to reduce their total energy and nutrient intakes. Recent analyses of clinical studies found that acidosis and dehydration were most closely associated with reduced dietary intake of hospitalized patients. The implications of these and other studies for the dietary management of patients during and after diarrhea are discussed. PMID- 1421930 TI - Lactose feeding during persistent diarrhoea. AB - Lactose intolerance is a recognized complication of some episodes of diarrhoea. Whereas it is of clinical importance in relatively few children with acute diarrhoea it seems to be a more common problem in children presenting with persistent diarrhoea, especially in malnourished children with severe diarrhoea. We describe a recent study which also demonstrated adverse clinical and nutritional consequences in the majority of children with mild but persistent diarrhoea consuming 6 g lactose/kg body weight/d. It is desirable to identify these children who need to reduce their lactose intake in order to limit unnecessary dietary changes which are expensive to implement and/or nutritionally disadvantageous. Admission clinical characteristics were analyzed for their ability to predict clinical outcome in a group of 33 children with persistent diarrhoea taking a lactose-containing diet. The results of tests of stool reducing substances and a lactose breath hydrogen test (LHBT) were analyzed in the same group whose clinical management had been independent of the test results. Eighty-nine percent of children who deteriorated had one of the following characteristics: age < 12 months, weight-for-height less than -2 SD below NCHS norms or fever > 37 degrees C. Children who unequivocally improved while continuing to take lactose could not be selected without the risk of including children who deteriorated. Neither tests of stool reducing substances nor the LBHT improved the predictive value of simple clinical parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421931 TI - Persistent diarrhoea: factors affecting absorption and clinical prognosis during management with a rice-based diet. AB - Twenty-six persistent diarrhoea patients aged 4 to 18 months were treated with a diet prepared with rice powder, soya oil, glucose, egg white and water. Absorption of macronutrients was estimated in a 72 h balance study and clinical response was examined during one week of dietary treatment. Nutrient absorption was compared with that of 25 healthy age-matched controls treated with the same diet. Twenty-one patients (81%) recovered from diarrhoea within seven days. Absorption of nutrients was significantly reduced among the persistent diarrhoea patients. More malnourished patients had a significantly reduced absorption of nutrients except carbohydrate and an increased severity and longer duration of diarrhoea. Total gut transit time had significant association with nutrient absorption in the persistent diarrhoea patients. The period of recovery negatively correlated with coefficient of absorption and positively with initial stool weight. Failure to recover was associated with severity of diarrhoea and systemic infection. The study indicates that nutrient absorption is significantly reduced in patients with persistent diarrhoea and nutritional status, and that initial purging rate and intestinal hurry are significantly related to the prognosis and nutrient absorption. PMID- 1421932 TI - Nutritional management of persistent diarrhea: factors predicting clinical outcome. AB - In a prospective study we randomized 102 male children (age 6-36 months) with persistent diarrhea to receive a traditional rice-lentil (Khitchri) diet and yogurt (K-Y) or a soy formula (alone for seven days and then in combination with K-Y for seven days). Of 73 children satisfying the study criteria, 66 were successfully treated and there were 7 treatment failures. There was poor concordance between parental accounts of severity of diarrhea or vomiting and that observed after admission. Significant risk factors associated with treatment failure included younger age (p < 0.005) and vomiting at presentation (p < 0.02). The greatest number of risk factors associated with delayed recovery (> 10 days) were identified during an initial evaluation period (the first 8 h after admission). These included greater severity of watery diarrhoea (p < 0.01) and increased ORS intake (p < 0.02). Our data suggest that an initial evaluation period, including objective observations, may identify children with persistent diarrhea who are at greatest need of hospitalization. PMID- 1421933 TI - Oral gentamicin is not effective treatment for persistent diarrhea. AB - We conducted a randomized, double-blind, placebo controlled clinical trial of oral gentamicin (10 milligrams/kilogram body weight/day for five days) in treatment of unselected cases of persistent diarrhea (duration 14-18 days at initiation of treatment) among 3-36-month-old children in a rural Guatemalan community. Following random assignment of each child to a treatment group, the appropriate dose of gentamicin or placebo was administered to the child three times daily by a study nurse; this nurse also identified the presence or absence of diarrhea on each day of treatment and for the next two days. Cure was defined as cessation of diarrhea during the five-day treatment period, sustained through at least the two days after completion of treatment. Among 92 evaluable cases who entered the clinical trial, there was essentially no difference in cure rate between gentamicin and placebo treatment groups (42% versus 43%). Enteroadherent strains of Escherichia coli were identified in 46% of children tested in this trial; no significant difference existed between treatment groups in frequency of isolation of this or any other enteropathogen. Among 40 children having successful duodenal cultures immediately prior to beginning treatment, > or = 10(4) aerobic organisms per milliliter of fluid were identified in 12 (30%); treatment groups did not differ substantially with respect to proportion of children identified with this level of duodenal microbial colonization. Failure of gentamicin treatment did not appear to be explained by emergence of resistance, although a small number of resistant enteropathogens were identified near the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1421934 TI - Epidemiological and clinical characteristics of acute and persistent diarrhoea in rural Bangladeshi children. AB - A community-based longitudinal study of acute and persistent diarrhoea in 705 children less than five years old was carried out for a year in a rural area of Bangladesh. Diarrhoea morbidity data were collected from each study child every fourth day by home visit. Clinical features of diarrhoeal episodes and diarrhoeal management information were documented. The overall diarrhoeal incidence rate in the study children was 4.6 episodes per child per year. The incidence of persistent diarrhoea was 34/100 child-years. Persistent diarrhoea was positively associated with young age and more severe illness, characterized by the presence of clinical dehydration or blood in the stool in the first week. Use of ORT in the first week was positively associated and use of an antibiotic was negatively associated with the occurrence of persistent diarrhoea. Reduced breast-feeding and consumption of cow's milk at some time during the episode were also positively associated with persistence. This would suggest that appropriate fluid and dietary management for all episodes should be the goal. Children with more severe initial illness characterized by the presence of blood in the stool or clinical dehydration should have more careful follow-up to identify persistent episodes and adverse nutritional effects. Breastfeeding should be continued during acute diarrhoea, but the role of ORT, antibiotics and cow's milk deserves further investigation. PMID- 1421935 TI - Epidemiology of persistent diarrhea among Guatemalan rural children. AB - A prospective, longitudinal two-year study to determine the epidemiology of persistent (> or = 14 days' duration) diarrhea in rural children of Guatemala was undertaken. Three-hundred and twenty-one children aged 0-35 months were kept under surveillance by twice-a-week home visits. The overall incidence of diarrhea was 0.147 per child-week; the incidence of persistent diarrhea was 0.014 per child-week. The peak of persistent diarrhea was observed in infants below six months of age, with a continuous decline thereafter. This trend in incidence of persistent diarrhea was associated with a higher proportion (16%) of illnesses persisting for more than 13 days in children younger than six months of age as compared to children 30-35 months old (4%). Males had more diarrhea (0.156 per child-week) than females (0.139 per child week). Among children above 18 months of age, the proportion of episodes that lasted for more than 13 days was lower in females than in males. PMID- 1421936 TI - Epidemiology of persistent diarrhea and etiologic agents in Mirzapur, Bangladesh. AB - To determine the epidemiology and etiologic agents of persistent diarrhea we carried out an intensive diarrhea surveillance on children less than six years old in rural Bangladesh. From March 1987 to February 1989 we examined 363 children through diarrhea recall interviews and analyzed stool samples of all diarrhea cases for potential pathogens. Results showed that children had an average of two episodes per year and the incidence rate of diarrheal episodes defined as acute (< 14 d) and persistent (> or = 14 d) varied similarly with age. The peak incidence (episodes/child/year) of acute diarrhea (2.8) and persistent diarrhea (0.8) occurred in the 6-11 months age group. The data showed that an episode tended to be prolonged if the stool was loose/mucoid or bloody at onset. Aggregative adherent Escherichia coli was found significantly more often at onset in persistent than in acute episodes, whereas Shigella, Aeromonas, Giardia and toxigenic E. coli were isolated with less frequency in persistent than acute episodes. This suggests that other factors might be more important in the development of persistent diarrhea than specific pathogens. PMID- 1421937 TI - Mortality associated with acute watery diarrhea, dysentery and persistent diarrhea in rural north India. AB - Mortality associated with diarrhea was investigated in a longitudinally followed cohort of children under six years of age in rural North India. During the follow up, 1663 episodes of diarrhea and 23 diarrhea related deaths were recorded in 1467 children followed up for 20 months. The case fatality rate was 0.56% for acute watery diarrhea, 4.27% for dysentery and 11.94% for non-dysenteric persistent diarrhea. Most of the episodes lasted less than a week; 5.2% became persistent (duration > 14 days). The case fatality rate was similar in episodes of one and two weeks' duration (0.64% and 0.8%) and increased to 13.95% for persistent episodes. Of the total 86 persistent episodes, 22.1% were dysenteric; the case fatality rate for such dysenteric persistent episodes was 21.1% and for watery persistent diarrhea 11.4%. Diarrheal attack rates were similar among different nutritional groups, but diarrheal case fatality rates progressively increased with increasing severity of malnutrition, these were 24 times higher in children with severe malnutrition (7.48%) compared to those normally nourished (0.31%). With availability and use of oral rehydration therapy, dysentery and persistent diarrhea emerge as major causes of diarrhea related mortality, with underlying malnutrition as a key associated factor. PMID- 1421939 TI - Persistent diarrhea in northeast Brazil: etiologies and interactions with malnutrition. AB - With the improved control of acute diarrheal illness mortality with oral rehydration therapy, persistent diarrhea is now emerging as a major cause of childhood mortality in tropical developing areas like the impoverished populations in Brazil's Northeast. "Graveyard surveillance" in the rural community of Guaiuba in northeastern Brazil revealed fully half of the 70% diarrhea mortality was due to persistent diarrheal illnesses. Furthermore, 11% of 14 or more diarrheal illnesses per child per year in an urban slum in Fortaleza persisted beyond 14 days, a definition that clearly identified the high risk children for heavy diarrhea burdens. Not only did heavy diarrhea burdens ablate the key "catch-up" growth seen in severely malnourished children and in children following previous diarrheal illnesses, but malnutrition significantly predisposed children to a greater incidence and duration of diarrhea as well as a greater incidence of persistent diarrhea. Etiologic studies of 37 children presenting with persistent diarrhea to Hospital das Clinicas in Fortaleza revealed that Cryptosporidium (in 13%) and enteroadherent E. coli (36% with aggregative, 29% with diffuse and 13% with localized adherence to HEp-2 cells) were the predominant potential pathogens found in the stool or upper small bowel. These findings suggest that persistent diarrhea is emerging as an important health problem in Brazil's Northeast, that it identifies a high risk child for heavy diarrhea burdens, that important interactions occur with malnutrition and that Cryptosporidium and enteroadherent E. coli warrant further study as potential etiologies of this major cause of morbidity and mortality. PMID- 1421938 TI - Etiologic agents in acute vs persistent diarrhea in children under three years of age in peri-urban Lima, Peru. AB - In a longitudinal study of acute and persistent diarrhea in 677 children less than three years old in a peri-urban community of Lima, Peru, during 27 months of surveillance, stools were cultured at the beginning of each diarrheal episode and on each subsequent week of illness. Analyzing stool cultures only from children who had not received antibiotic treatment in the 48 h prior to the culture, no association was found between any enteropathogen and persistent diarrhea. We did not find any increase in mixed infections in persistent diarrhea episodes as compared with acute diarrhea, controlling for age, season and anthropometric status. The isolation rate for any given enteropathogen was similar during the first, second, third or later week of illness, but when the presence of a specific enteropathogen was sought in sequential stools within a single episode, no evidence of persistent infection was found. This study shows that in developing countries with a high incidence of diarrheal diseases frequent re infections with enteropathogens prevalent in the population are one reason for prolonged illnesses. Host factors that increase susceptibility to infection or decrease recovery from illness may also play a role. Further studies of these factors, such as micronutrient deficiencies, are needed to identify a public health intervention to control persistent diarrhea, a condition associated with mortality in many developing countries. PMID- 1421940 TI - Persistent diarrhea associated with AIDS. AB - Chronic diarrhea and wasting are very common manifestations of AIDS in adults in developing countries. Etiologic studies show that protozoa (including Cryptosporidium parvum, Isospora belli, and Enterocytozoon bieniusi) and Mycobacterium avium-intracellulara are the most frequently identified pathogens. Limited data in children suggest that common enteric pathogens are equally as likely in HIV+ and HIV- babies. Preliminary analysis of an ongoing longitudinal study of 469 babies born to mothers with known HIV serostatus in Kinshasa, Zaire, reveals progression of acute to persistent diarrhea is six times greater in HIV+ compared to HIV- babies, and 3.5 times greater in HIV- babies born of HIV+ mothers in comparison to HIV- babies with HIV- mothers. HIV+ babies were also at greater risk than HIV- babies to have recurrent episodes of diarrhea (RR = 2.3). Fifty percent of the deaths were due to acute or persistent diarrhea, and were strongly associated with HIV infection. Efforts to improve child survival in AIDS infected populations will need to address HIV infections in both mothers and infants. PMID- 1421941 TI - Household behaviors in the management of diarrhea and their relevance for persistent diarrhea. AB - There has been a great deal of research in recent years on household behaviors related to diarrhea management. Most of the available data on household diarrhea management, however, pertains to acute diarrheal episodes. There is a dearth of knowledge concerning household and caretaker behaviors when the diarrhea is of longer duration. This paper briefly reviews some of what has been learned about household behaviors in the management of acute diarrhea and discusses its relevance for persistent diarrhea. Based upon what has been learned from anthropological studies of acute diarrhea and the little that is known about caretaker behavior during persistent diarrhea, a hypothetical model of the interactions among household behavior and characteristics of diarrheal episodes is presented. The model argues that maternal (or caretaker) concern increases with diarrheal duration, and that changes in behavior, both adaptive and maladaptive, are more likely to occur during an episode of persistent diarrhea, compared to acute. In some cases, these actions may directly influence the outcome of the episode. There is a need to better understand household case management behaviors through the continuum of diarrheal duration and the effect of these behavioral factors on episode outcome. This information is necessary in order to communicate effective messages to caretakers about what they should know and what they should do when persistent diarrhea occurs. PMID- 1421942 TI - The child's disease (Doenca de crianca): popular paradigm of persistent diarrhea? AB - According to popular report, the folk illness, Doenca de crianca (The Child's Disease) is the leading cause of infant and childhood death in Northeast Brazil; most health professionals, however, are unaware it exists. Doenca de crianca is described based on ethnographic interviews with 50 traditional healers and 50 bereaved mothers whose children have died from the condition. Doenca de crianca is a sociocultural label developed by the popular medical system and applied to the end stages of severe childhood infectious diseases and malnutrition against a background of grinding poverty. Doenca de crianca is discussed as an analog to persistent diarrhea. Practical treatment and management implications of this relationship are presented. Doenca de crianca, most importantly, offers a new, holistic paradigm for the future study of persistent diarrhea. PMID- 1421943 TI - Association of indicators of hygiene behavior with persistent diarrhea of young children. AB - We examined the association between water and hygiene-related behaviors and persistent diarrhea (duration > or = 14 days) among children under age three years in an indigenous rural Guatemalan community. Behavior indicators were specific aspects of the appearance of the mother, study child, other children and household that could be observed using a spot observation technique. Thirty-four percent of children had one or more episodes of persistent diarrhea during the year of study. Bivariate analyses found that a higher proportion of observations in which the anti-hygienic condition was observed was significantly associated with persistent diarrhea for 11 of 26 behavior indicators; these 11 indicators were also strongly correlated with each other. In individual logistic regression models, which included overall rate of diarrhea and other child characteristics associated with persistent diarrhea, six behavior indicators maintained significant association with persistent diarrhea: presence of toy on the ground, presence of baby bottle on the ground, the hands of the mother being dirty, presence of a fecally soiled diaper on the ground in the household compound, presence of feces in the yard, and the study child wearing a fecally soiled diaper. Three additional indicators closely approached significant association with persistent diarrhea. Excluding the three soiled diaper indicators, which might be the result rather than the cause of diarrhea, we found the six other behavior indicators to demonstrate a significant dose-response effect in increasing risk of persistent diarrhea. These findings suggest that behaviors which promote increased exposure of young children to enteric pathogens increase risk of persistent diarrhea. PMID- 1421945 TI - Small intestinal mucosal histology in the syndrome of persistent diarrhoea and malnutrition: a review. AB - Prolonged injury to the small intestinal mucosa is probably the final common pathway by which a variety of noxious influences--nutritional, infective and possibly allergic--perpetuate the syndrome of persistent diarrhoea in children in developing countries. Animal studies have helped to separate the individual effects of malnutrition and diarrhoea on the gut in a way that is not possible in the clinical situation. Early studies in children provided somewhat subjective or semi-quantitative data on intestinal morphology. More recently, the application of computer-assisted quantitative morphological techniques to intestinal mucosae from children with persistent diarrhoea have revealed a spectrum of changes consistent with a cell-mediated immune form of damage. The nature of the antigens that provoke these responses remains to be elucidated. Several reports indicate that in children with persistent diarrhoea clinical severity and prognosis do not necessarily correlate with the degree of small intestinal mucosal damage. Nutritional rehabilitation can be shown to produce a demonstrable improvement in small intestinal crypt cell proliferative activity in children with persistent diarrhoea. It is not yet known for how long nutritional rehabilitation should be continued to ensure complete recovery of the intestinal damage following persistent diarrhoea. PMID- 1421944 TI - Deaths due to dysentery, acute and persistent diarrhoea among Brazilian infants. AB - In a population-based study, all infant deaths occurring in a one-year period in the metropolitan areas of Porto Alegre and Pelotas, in southern Brazil, were studied. There were 227 infants who presented diarrhoea during the fatal illness, and in 75% of these diarrhoea was considered to be the underlying cause of death. Acute diarrhoea (< 14 days' duration) accounted for 28% of the deaths, persistent diarrhoea for 62% and dysentery for a further 10%. Approximately one-half of the children with persistent diarrhoea were admitted to a hospital in the first two weeks of the episode. Hospital-acquired infections were likely to have contributed to one- to two-thirds of deaths due to dysentery and persistent diarrhoea. A comparison with neighbourhood controls showed that breast milk provided substantial protection against deaths due to either acute or persistent diarrhoea. PMID- 1421946 TI - Dietary protein sensitivity: is it an important risk factor for persistent diarrhea? AB - Although the causes of persistent diarrhea are largely unknown, dietary protein sensitivity has been identified as one possible mechanism. Since nutritional therapy appears to be an essential component of treatment for persistent diarrhea, a clearer understanding of the importance of dietary protein allergy is needed to provide optimal dietary recommendations. This paper reviews the current concepts of the pathophysiology, clinical features and criteria for diagnosis of dietary protein sensitivity. Evaluation of the results of several clinical studies indicates that dietary protein sensitivity does occur especially in young infants fed cows' milk but that it is an uncommon event, especially in older infants and children. PMID- 1421947 TI - Zinc and diarrhea. AB - Malnutrition is a major factor in the etiology, management and prognosis of persistent diarrhea in young children. Apart from inadequate energy intake, deficiencies of several specific nutrients have been implicated. Zinc is a micronutrient that appears to be of special interest, at least in some communities. Zinc deficiency has been documented in otherwise normal children. The risk of deficiency, however, is enhanced by diarrhea which is associated with variable but sometimes gross increases in zinc losses in the feces. These losses could contribute to a vicious circle, as there is now evidence that mild as well as severe zinc deficiency states can contribute to the duration and severity of diarrheal disease. During rehabilitation, impaired zinc nutriture could be responsible for slow growth, especially if the rehabilitation diet is high in phytate, a recognized inhibitor of zinc absorption. Research should be directed to a better understanding of zinc metabolism and homeostasis during diarrhea disease, to the consequences of zinc deficiency and to the benefits to be derived from zinc supplementation programs. PMID- 1421948 TI - Effect of milk-containing diets on the severity and duration of childhood diarrhea. AB - Individual components of milk from humans and other mammalian species may influence the severity, duration, and nutritional outcome of childhood diarrhea in different ways. Nonetheless, empirical data from clinical trials can be used to assess children's responses to specific milk-containing diets. Factors modifying the response to milk include its source, amount, frequency of feeding, type of processing, and accompanying foods, as well as the type and severity of enteric infection and specific characteristics of the host. Whereas breast-fed infants have less severe diarrhea when breast milk is continued rather than interrupted, infants and children fed with non-human milks tend to have more severe illness than those receiving milk-free or lactose-limited formulas or milk cereal mixtures. Fermentation of milk may reduce the severity of lactose malabsorption, but additional information regarding the efficacy of yogurt in acute, childhood diarrhea is still needed. PMID- 1421949 TI - Type of milk feeding during acute diarrhoea and the risk of persistent diarrhoea: a case control study. AB - The role of feeding breast milk, unmodified bovine milk or adapted infant formula during acute diarrhoea in protecting against or causing persistence of the episodes was investigated in a population-based case control study in an urban area of north India. After adjustment for confounding variables, exclusive breast feeding was associated with an odds ratio of 0.06 (95% CI 0.002-2.1), a 16.5 times lower odds in favour of developing persistence of an episode. Infants fed unmodified bovine milk in addition to breast milk had an odds of 2.5 times (95% CI 1.0-9.9) in favour of developing persistence of acute diarrhoea (p = 0.04). In infants receiving unmodified bovine milk and no breast milk, this odds ratio was 11.1 (95% CI 1.0-228.8) (p = 0.05). This study indicates that promoting exclusive breastfeeding may reduce the persistence of diarrhoea over and above its effect in decreasing the incidence of acute diarrhoea. In urban areas of the developing countries where working mothers often use milk supplementation beyond the age of three months, our findings suggest that use of adapted spray dried formula may be safer than unmodified bovine milk with respect to the risk of developing persistent diarrhoea. PMID- 1421950 TI - Feeding during acute diarrhea as a risk factor for persistent diarrhea. AB - Dietary intake during diarrhea in children less than three years of age was estimated from information recorded on illustrated dietary forms used by children's caretakers during the first week of illness in a prospective community based study of diarrheal diseases in Lima, Peru. The frequency of consumption and the amount consumed of food groups and selected commonly consumed foods were analyzed by the final duration of the diarrheal episode. Cereals were less frequently consumed during the acute phase of diarrheal episodes that ultimately became persistent (> 14 days' duration), apparently shortening the duration of the episode by one day (median duration of four days in children not consuming vs three days in children consuming cereals during diarrhea, p < 0.02 Kaplan-Meier log-rank test). Only roots and tubers (mainly potatoes) were consumed in greater quantity during episodes that became persistent. There was no evidence that consumption of breast milk or non-maternal milk was associated with an alteration in diarrheal duration. This study provides further evidence of the beneficial effects of continuing feeding during diarrhea using foods available at the home level, especially cereals, which are commonly used in the diet of young children. PMID- 1421951 TI - Management of extremely low-birth-weight infants. AB - Better health care of women during pregnancy and delivery, improvement in neonatal intensive therapy and technology have led to a decrease in neonatal mortality and morbidity and to lower limits of birth weight and gestational age for survival. This paper refers to the management protocol used in the Department of Perinatal Pathology of the Provincial Maternity Hospital of Milan for extremely low-birth-weight (ELBW) infants (birth weight < 1000 g). In this hospital, all newborn infants presenting evidence of life, irrespective of birth weight and gestational age, are resuscitated and transferred to the Neonatal Intensive Care Unit (NICU) for clinical management. After the introduction of this protocol the mortality rate of ELBW infants dropped from 71.4% in 1977-78 to 48% in 1987-88. In a group of 72 ELBW infants with a mean birth weight of 850 g and a mean gestational age of 27 weeks, 80% presented a normal outcome, 12% presented a mild neurological impairment and 8% were affected by severe cerebral palsy at the age of two years. The intact survival of a newborn infant of 450 g at birth is also reported. PMID- 1421952 TI - Hospital care techniques resulting in intact survival of a 380-g infant. AB - Intact survival of infants delivered before completion of the 26th week of gestation or weighing less than 500 g is a well known phenomenon. We recently cared for an infant whose birth weight was 380 g, making her one of the smallest survivors in the United States. Her hospitalization (including expenses), the techniques of our minimal intervention protocol and her 20-month (corrected) follow-up are presented together with a discussion of the moral, economic and social implications involved in the care of such an infant. PMID- 1421953 TI - Intact survival of a 280-g infant: an extreme case of growth retardation with normal cognitive development at two years of age. AB - The care of infants born weighing less then 500 g is not only controversial but is also associated with medical uncertainties. We report the management of a growth retarded infant who weighed 280 g at birth after 26.9 weeks' gestation. The child not only survived but appears developmentally normal at two years of age. Although the infant is the smallest survivor reported, the case demonstrates the importance of gestational assessment in deciding delivery room management. PMID- 1421954 TI - The care of fetal babies: survival of a 390-g infant. AB - Infants with birth weight 750 g or less usually have a poor survival rate, and those who live have poor neurologic and intellectual outcome. With significant advances in perinatal care and meticulous neonatal support, the survival of these babies has improved in recent years and the long-term outcome can be as good as that of larger low-birth-weight infants. It is likely that the reported increase in survival of ELBW infants reflects a changing obstetrical approach to the extremely premature fetus along with an increased attitude among pediatricians and neonatologists to treating such babies. This posture is motivated and supported by a number of factors, including regional systems of perinatal care that encourage early maternal transport to tertiary centers, an increasing ability of neonatal intensive care technology to achieve survival, and more optimistic long-term neurodevelopmental outcome reports. Our experience is encouraging in this regard. This presentation reports the survival of an ELBW infant delivered in Switzerland before the completion of the 26th week of gestation and weighing 390 g at birth. PMID- 1421956 TI - Window of vulnerability of vaccinia virus-infected cells to natural killer (NK) cell-mediated cytolysis correlates with enhanced NK cell triggering and is concomitant with a decrease in H-2 class I antigen expression. AB - A time course study was performed in order to determine if vaccinia virus (VV) infected targets were more susceptible to murine natural killer (NK) cell mediated lysis during a discrete period of time postinfection. Activated NK cells were used in short-term (e.g. 4 h) assays in order to avoid a further in vitro activation of the NK cells by interferon (IFN) and to test the innate susceptibility of target cells to lysis. The sensitivity of VV-infected L929 cells to lysis by NK cells increased as the infection progressed, reached a peak at approximately 24 h postinfection, and subsequently declined to levels lower than that of uninfected cells. This window of vulnerability was not due to an increase in the number of effector/target cell conjugates, which continually decreased as the VV infection progressed. Triggering of NK cells was measured by the influx of 45Ca2+. Target cells treated with IFN induced less 45Ca2+ uptake, whereas cycloheximide treatment of targets caused a greater influx of 45Ca2+ into the effector cells. When L929 cells were infected with VV for various time intervals and used in the triggering assays, an enhanced triggering of the effectors corresponding to the time of enhanced susceptibility of the target cells to lysis was detected. Quantitative decreases in H-2Kk and Dk class I antigens were observed following VV infection of target cells as measured by FACS analysis using alloantibodies. Qualitative changes in H-2 class I antigens were also observed, as detected by a loss in VV-infected target cell susceptibility to lysis by allospecific cytotoxic T lymphocytes (CTL) at a time when they were highly sensitive to killing by NK cells and VV-specific CTL. These results show that virus-infected targets may become innately more sensitive to lysis by NK cells at discrete time points after infection and that the susceptibility to lysis correlates with enhanced triggering of NK cells and reduced H-2 class I antigen expression. PMID- 1421957 TI - Nursing is not just the tasks nurses do. PMID- 1421955 TI - Tissue distribution of adoptively transferred adherent LAK cells: role of the route of administration. AB - The ability of LAK and adherent LAK (A-LAK) cells to migrate to and localize into tumors might be a limiting factor for the efficacy of adoptive immunotherapy. Employing different routes of inoculation of A-LAK cells labeled with 125IUdR, we have investigated how murine A-LAK cells circulate in the bloodstream and localize into various tissues. After intravenous injection, most of the A-LAK cells migrated to the lungs with less than 15% redistributing to other organs. Following left ventricular inoculation, after which the injected cells do not have to pass the lung capillaries before reaching other organs, higher numbers of A-LAK cells were found in liver, carcass, kidney and gut compared to intravenous injection. However, most of the A-LAK cells were cleared from these organs within 24 h, and surprisingly at this time the overall survival of the injected A-LAK cells was not more than 10-20% regardless of the route of injection. We found that a substantial accumulation of A-LAK cells in the liver could be achieved only when the cells were injected directly into the portal vein. Following this route of administration, more than 40% of the injected A-LAK cells were still in the liver at 24 h, whereas only 3-5% had redistributed to other organs. Our data suggest that A-LAK cells circulate inefficiently and survive poorly following systemic administration. However, enhanced accumulation of these cells in a particular organ might be achieved by direct administration of the A-LAK cells into the vessels feeding the organ. PMID- 1421958 TI - The most important needs of parents of critically ill children: parents' perceptions. AB - Research studies have identified the needs of relatives when they have had an adult family member in the intensive care unit. However little similar work has been done within the paediatric setting. Therefore the aim of this study was to examine what parents considered to be their most important needs, when they have a child ill in the intensive care environment (PICU). A questionnaire was designed, and was distributed to parents of 30 children admitted into a PICU. The questionnaire identified needs items which may be important to parents of sick children. The parents were required to indicate how important each need was to them during the time of the child's stay in the PICU. Results obtained indicate that parents have a strong need for information and relief of anxieties that they may have about their child's condition. A conclusion reached in this study is that if the critical care staff can go some way to assess and meet the needs of parents of critically ill children, then these parents may be more able to become effective partners in care, which may have therapeutic effects upon the child's health recovery. PMID- 1421959 TI - The nurse's role in organ donation from a brainstem dead patient: management of the family. AB - This paper suggests ways in which the nurse in charge of a brainstem dead patient can help in the management of the patient's family so that they can more easily and effectively come to terms with his or her death and consider the possibility of organ donation. Many nurses, in spite of their basic training, are unprepared to assume such a role successfully, and three areas are preliminarily identified for closer study, i.e. 1) the preparation of the family for brainstem death, 2) the approach to the family for possible organ donation, and 3) the care of the family throughout the process of organ donation. Certain recommendations are suggested which might help to promote the necessary caring approach to the problem. Review of literature on the nurse's role in such a situation shows how important that role is thought to be. Guidelines are tentatively laid down for explaining brainstem death and preparing the family for it; and the importance of their acceptance of the finality of death is stressed, so that they can begin the essential grieving process. Emphasis is also laid on the need for the nurse to adopt a sensitive, caring and supportive attitude which will help the family in their bereavement and encourage them to accept the possibility of organ donation. In conclusion, it is recommended that nurses be provided with more detailed advice and guidance on managing the family in the many aspects of such a situation. PMID- 1421960 TI - The applicability of a new sedation scale for intensive care. AB - Experience of the sedation scale, which was in use for the assessment of ventilated patients, in an intensive care unit revealed a number of deficiencies. Discussion suggested that an ideal scale should be more straightforward and easily understood by all levels of staff. It should also relate closely to the behaviour of the ventilated patient, and allow an optimal level of sedation; where the patient receives the minimum level of medication to allow pain and stress-free ventilation. A scale was devised with explanations of each level, and was incorporated in a revised sedation policy. In practice this was found to be an improvement over the scale that had been used previously. PMID- 1421961 TI - Pain following coronary artery bypass grafting: an exploration of contributing factors. AB - Patients suffer pain and discomfort in ICU following coronary artery bypass grafting (CABG). While the surgical procedure causes pain, it is the psychological state of the individual which influences his perception of the pain. For the patient undergoing cardiac surgery, several stressors may influence his psychological state, including coronary heart disease (CHD) itself, impending surgery and the intensive care unit (ICU) environment. The types of pain caused by the surgical procedure are discussed. Each of these aspects are brought together in an attempt to gain a better understanding of the patient's perspective of cardiac surgery, and any pain experienced as a result. Given the major influence of the patient's mind in pain perception, there is a need for nurses to consider alternative methods of pain relief in addition to drug therapy. PMID- 1421962 TI - Inotropes--an overview. AB - It is essential that nurses understand the drugs they are using, and the measurements they are monitoring. Inotropes are powerful drugs with immediate action. The aim of this article is to give an overview of the inotropes used commonly in intensive care environments, plus some of those currently undergoing investigation. PMID- 1421963 TI - Retention of advanced cardiopulmonary resuscitation knowledge by intensive care trained nurses. AB - The teaching and reinforcing of advanced cardiopulmonary resuscitation (ACPR) is an important part of the role of an intensive care nurse manager. This study highlights the need for a structured training programme, as well as regular updates in ACPR. Current research shows poor retention of CPR skills amongst nursing staff. A small study was undertaken amongst intensive care trained nurses at The Middlesex Hospital intensive care unit (ICU). 18 nurses took part in the study, and were each interviewed with regard to their knowledge of ACPR in December 1990. The period of time since last trained in ACPR ranged from 2 months 4 years. Those who had been recently updated in ACPR (up to 4 months prior to interview) scored higher than those who were updated more than 2 years ago. The results showed that most nurses interviewed were only able to answer correctly half the questions asked. These results indicate that the nurses in the study generally demonstrated a severe lack of knowledge of ACPR. This indicates the need for a structured training package in ACPR, followed by frequent reinforcement of ACPR knowledge and skills for nurses practising in an ICU environment. PMID- 1421964 TI - A literature review of recent advances in enteral feeding and the increased understanding of the gut. AB - This literature review focuses on recent advances in enteral feeding and increased understanding of the role of the gut. The gut is beginning to be seen as a reservoir for bacteria and a source which contributes to multi-organ failure (MOF) due to translocation of bacteria, in addition to its usual functions. Enteral feeding as discussed in this article is a method of feeding which frequently involves nurses at the bedside, yet so many seem unfamiliar with recent research on the topic. A simple change to intermittent enteral feeding could be more beneficial for patients than continuous feeding. Indeed, continuous feeding may even be harmful, and as Florence Nightingale stated in her book Notes on Hospitals in 1858, hospitals should do no harm to patients. PMID- 1421966 TI - Mutagenic activity of copper(II) chromate and dichromate complexes with polypyridines. AB - Copper(II) chromate and dichromate complexes with 2,2'-bipyridyl and 1,10 phenathroline were tested for their mutagenic activity in the standard Ames test. All of six tested complexes exhibited markedly lower mutagenic activity than the reference compounds--potassium dichromate and sodium chromate. The blockage of Cr(VI) reduction capability in the presence of the complex Cu2+ ion and the competition between copper and chromium ions in the interaction with cellular components are discussed in the light of the results of our previous chemical study. PMID- 1421967 TI - Modulation of chromium(VI) toxicity by organic and inorganic sulfur species in yeasts from industrial wastes. AB - Two chromium(VI) resistant yeast strains (Candida sp. and Rhodosporidium sp.) were isolated from industrial wastes. Four different yeasts, three from the Industrial Yeast Collection and one of pharmaceutical origin, were also studied in relation to chromate toxicity and its alleviation by sulfur species. The growth of yeasts from industrial wastes was inhibited by 50% by high concentrations of Cr(VI): Candida sp. by 4 mM Cr(VI) and Rhodosporidium sp. by 10 mM Cr(VI) in Sabouraud Broth medium. The other Cr(VI)-sensitive yeasts were inhibited by 0.1 mM Cr(VI). The general mechanism of chromium resistance in Candida sp. and Rhodosporidium sp. was due to reduced uptake of chromium, but not to biological reduction from Cr(VI) to Cr(III). In Cr(VI)-sensitive yeasts, chromium was accumulated as much as 10-fold, as in Saccharomyces cerevisiae. Cr(VI) toxicity in Candida sp. was modulated from Cr(VI)-resistance to Cr(VI) hypersensitivity depending on the addition of methionine, cysteine, sulfate and djenkolic acid. If Candida sp. was grown in the presence of S-amino acids, especially methionine, it was more resistant than if the sulfur source was sulfate. When sulfate transport was enhanced by addition of djenkolic acid, Candida sp. became hypersensitive. Rhosporidium sp. was always resistant to Cr(VI) because sulfate transport was inefficient and it assimilated sulfur as S amino acids. Cr(VI)-sensitive yeasts required larger amounts of S-amino acids, especially methionine, to tolerate Cr(VI) toxicity. Cysteine was toxic for C.famata 6016 above 50 microM. PMID- 1421965 TI - An iron-sulfur cluster plays a novel regulatory role in the iron-responsive element binding protein. AB - Post-transcriptional regulation of genes important in iron metabolism, ferritin and the transferrin receptor (TfR), is achieved through regulated binding of a cytosolic protein, the iron-responsive element binding protein (IRE-BP), to RNA stem-loop motifs known as iron-responsive elements (IREs). Binding of the IRE-BP represses ferritin translation and represses degradation of the TfR mRNA. The IRE BP senses iron levels and accordingly modifies binding to IREs through a novel sensing mechanism. An iron-sulfur cluster of the IRE-BP reversibly binds iron; when cytosolic iron levels are depleted, the cluster becomes depleted of iron and the IRE-BP acquires the capacity to bind IREs. When cytosolic iron levels are replete, the IRE-BP loses RNA binding capacity, but acquires enzymatic activity as a functional aconitase. RNA binding and aconitase activity are mutually exclusive activities of the IRE-BP, and the state of the iron-sulfur cluster determines how the IRE-BP will function. PMID- 1421969 TI - [Exploration on English translation of basic theoretical term of traditional Chinese medicine]. PMID- 1421968 TI - Analogous copper(I) coordination in metallothionein from yeast and the separate domains of the mammalian protein. AB - The three-dimensional structures of both vertebrate Cu12-metallothionein (class 1) and yeast Cu8-thionein (class 2) are still unknown. The different copper:protein stoichiometry compared with that of the (ZnCd)7-metallothioneins was expected to alter the metal-thiolate cluster structure considerably. In order to avoid possible domain interactions in the hepatic rat metallothionein, separate chemically synthesized alpha- and beta-domains were used rather than the apoprotein. Apo yeast thionein, and the alpha- and beta-domains of rat liver metallothionein-2 were reconstituted by Cu(I) titration. Reconstitution steps were monitored using spectroscopic methods including luminescence emission and circular dichroism. Upon UV irradiation a linear increase in intensity of the orange-red luminescence was observed near 600 nm up to 6 Cu eq using either compound regardless of the different cysteine sulfer content (yeast thionein 12S, alpha-domain 11S, beta-domain 9S). The characteristic dichroic properties of the yeast copper-protein between 240 and 400 nm were in good agreement with those of the respective class 1 metallothionein domains. All observed Cotton bands were of similar shape and appeared in the same wavelength regions. However, the molar ellipticities were less pronounced in the alpha- and beta-fragments employed. There appears to be a striking similarity between the oligonuclear Cu(I) binding centers in all metallothionein species. PMID- 1421970 TI - [Clinical study of yi shen ning for treatment of kidney-yang deficiency after hormone withdrawal of primary nephrotic syndrome--clinical analysis of 100 cases]. AB - This paper reports that Yi Shen Ning (YSN) which acts as warming and tonifying Kidney-Yang was administrated on 100 cases of primary nephrotic syndrome (PNS) while adrenocortical hormone (ACTH) was diminished to half dosage. The results showed that to apply the integrated TCM and WM according to the different stage of PNS was quite effective to treat deficient syndrome of Kidney-Yang appeared after withdrawal of ACTH. This recipe not only could improve the symptoms, but also pick plasma cortisol up earlier than expected, which was inhibited by exogenous hormone. The total remission rate of YSN group was 68.75%, higher than that of ACTH group (P < 0.05), especially for the cases dependent on exogenous hormone, the re-acquired remission rate reached to 58.3%. PMID- 1421972 TI - [Effect of Cordyceps sinesis on T-lymphocyte subsets in chronic renal failure]. AB - Synchronous measurements of renal function and T-cell subsets were taken in 51 cases of chronic renal failure (CRF) patients. Cordyceps sinesis 3-5 g/d was given to 28 out of these 51 patients, which was considered as follow-up group. The results were stated as follows: (1) Obvious decrease of OKT3, OKT4, OKT4/OKT8 was found in CRF (P < 0.01). (2) OKT4 and OKT4/OKT8 were proportional to plasma albumin and Hb levels (P < 0.05). (3) After administration of Cordyceps sinesis, improvement of renal function and OKT4, OKT4/OKT8 were confirmed. This study indicated that cellular immune function was decreased in CRF. Administration of Cordyceps sinesis might improve their renal function and as the same time enhance the cellular immune function in CRF. PMID- 1421971 TI - [Preliminary experimental and clinical study of the treatment of chronic renal insufficiency by granule of yi-qi bu-shen]. AB - The effects of the granule of Yi-Qi Bu-Shen on the chronic renal insufficiency (CRI) was studied. 30 cases of CRI patients using the granule was compared with other 23 CRI patients by using Aldehyde-coating Oxidated Starch in same conditions. The effective rate of these 2 groups were 53, 3% and 42.9% respectively (P > 0.05). According to laboratory observation, the granule had the ability to reduce BUN, Scr, Ch, TG and increase Ccr, Hb. The granule also could relieve symptom of Kidney-deficiency. Animal experimental research suggested the granule had the function of reducing BUN, Scr and could improve pathological changes in rat kidneys. The conclusion were that the granule was effective on treating CRI and could postpone the progress of CRI. PMID- 1421973 TI - [Long-term effect of Schonlein-Henoch nephritis with nephritic-nephrotic syndrome in children by traditional Chinese medicine and Western medicine]. AB - 21 cases are fully agreed with the diagnosis standard of Schonlein-Henoch nephritis. Biopsy on the kidney of 5 cases with resistant duration was made and all were diagnosed as mesenteric hyperplastic glomerular nephritis, among them, one with segmental sclerosis, one with segmental sclerosis and crescents in some glomerulus. 13 cases were treated with prednisone, cyclophosphamide and Traditional Chinese herbs. 8 cases with wilfordine adding and/or traditional Chinese herbs. The results showed that 15 of 21 cases were cured, one case perfect remission, 4 cases part remission. All of the cases were followed-up from 2 years and 10 months to 12 years and 4 months, average 7.34 years. The late results: Group A, 16 cases with symptom, physical exam, urine routine normal. Group B, 4 cases with microscopic hematuria and/or "a little-(+)" urinary protein. Group C, one case with "+2" urinary protein and/or hypertension, urinary creatinine clearance rate normal. Of 5 cases, whose biopsies of kidney were made, one with glomerular segmental sclerosis belonged to Group B. 13 of 21 cases had recurrence for 1-6 times, which was closed related with up respiratory tract infection. PMID- 1421974 TI - [Treatment of purpuric nephritis in children with Tripterygium wilfordii and radix Salviae miltiorrhizae]. AB - This paper dealt with the data of Tripterygium wilfordii polyoglucoside (1 mg/kg.d) combined with Radix Salvaie multiorrhizae (6-15 g/d) for treating purpuric nephritis (group-A), compared with the control group of using Tripterygium wilfordii polyoglucoside treatment only (group-B). The average time of edema-disappearing and blood pressure-resuming to normal range were 8.72 +/- 3.07 and 7.44 +/- 5.17 days in group-A, which were much better than those in group-B (P < 0.05). The average time of blood urine-disappearing in group-A and group-B were 36.37 +/- 11.50 and 47.73 +/- 14.03 days respectively. The average time on C3 in the urine resumed to normal in groups A and B were 40.33 +/- 4.51 and 50.00 +/- 5.30 days respectively (P < 0.01). The time of microcirculation of nail fold returned to normal after treatment in group-A and group-B were 39.00 +/ 11.03 and 66.00 +/- 9.01 days respectively (P < 0.001). These results indicated that the effect of group-A was much better than that of group-B. PMID- 1421975 TI - [Salvia miltiorrhizae in the treatment of the viral myocarditis]. AB - In Order to evaluate the effect of Salvia miltiorrhizae (SM) on the acute viral myocarditis (AVM), 60 children with AVM were studied. The patients were divided in random into two groups, group 1 treated with vit. C, ATP, CoA (n = 30), group II with SM plus vit. C, ATP, CoA (n = 30). The levels of plasma lipid peroxide (LPO), erythrocyte membrane microviscosity (EMMV), LDH, CPK, GOT and ECG in each patient were determined before and after one course of treatments respectively. The results revealed that before treatment the levels of plasma LPO and EMMV in both groups increased significantly compared with those of normal controls (n = 30, P < 0.01) respectively. There was a close correlation between LPO and EMMV (r = 0.6774, P < 0.01) and a close correlation between LPO and LDH (r = 0.5703, P < 0.01). After one course, the levels of plasma LPO and EMMV in both groups decreased significantly (compared with those before treatment, P < 0.01, respectively). But the LPO level and EMMV in group I were much higher than those in normal controls yet (P < 0.05, respectively). And LDH, GOT and ECG in nearly half of the patients in group I did not recover after one course while most patients in group II recovered. The results suggested that free radical plays an important role in the pathogenesis of AVM. SM as a good antioxidant, could protect myocardium from repairing membrane damage and clearing away free radical. This provided a new approach to treatment of viral myocarditis. PMID- 1421976 TI - [Reduction of genotoxic damage in oral mucosa with myasthenia gravis by traditional Chinese medicine]. AB - Micronucleated exfoliated cell (MEC) of oral mucosa of 40 patients with myasthenia gravis (MG) and 54 normal controls were observed by means of micronucleus test. The frequency of MEC of two groups were 9.56/1000 and 2.55/1000 respectively, and their difference was remarkably significant (P < 0.001). 22 cases were treated by TCM Qiang Ji Jian Li Capsule. The frequency of MEC after treatment fell from 14.38/1000 to 6.00/1000. The difference was significant (P < 0.002). The frequency of Spleen-asthenia group higher than that of non-Spleen-asthenia (P < 0.05). The results revealed that. The patients with MG had genotoxic damage. (2) The constitution with the Spleen-asthenia and the genotoxic damage was related. (3) Qiang Ji Jian Li Capsule of invigorating the Spleen and benefiting Qi could reduce the genotoxic damage. PMID- 1421977 TI - [Couch-netting operation for dislocation of adult lens]. AB - Clinical data of 12 adult cases of dislocation of lens treated with couching netting operating were analysed, including cases of traumatic cataracts with complications of glaucoma and cataract couching surgical complication of phacolysis. The result was rather satisfactory. Eye sight was corrected, most of the corrective vision was over 0.5 level, intraocular pressure was controlled and no serious complication was found. According to the authors experience, couching netting was recommended as a simple and effective method for treating dislocation of adult lens. PMID- 1421979 TI - [Experimental study of preventing liver cirrhosis by using four kinds of Chinese herbs]. AB - 55 rats were divided into six groups; (1) normal control, (2) cirrhosis control, (3-6) Chinese herbs groups, 2-6 groups were liver cirrhosis model caused by combined factor dominated by CCl4, and 3-6 groups were given Chinese herbs simultaneously until the end of sixth week. Radix Salviae miltlorrhizae (RSM) were used in group 3, Flos Carthami (FC) in group 4, Radix Angelicae sinensis (RAS) in group 5, Semen persicae (SP) in group 6. THE RESULTS: in group 2, 7 out of 9 rats developed into cirrhosis, the degree of fibrosis was 2.55+ and collagen protein content was 35.3 mg/g.liver, SGPT 387u. In group 3(RSM), no cirrhosis was found, the degree of the fibrosis was 0.43+ (compared with group 2, P < 0.01, collagen protein content was 16.7 mg/g.liver (P < 0.01), SGPT 132u (P < 0.01). In group 4(FC), 8 out of 9 rats did not develop into cirrhosis, collagen content 21.1 mg/g.liver, compared with group 2, P < 0.05. In the group of 5 and 6, some rats were developed into cirrhosis. The result showed that RSM and FC possessed an inhibitory effect on fibrogenesis. The effect of RSM was remarkable. It could prevent experimental cirrhosis. The effect of RAS and SP were uncertain. This experiment predicted that RAM would become the promising drug to restrain chronic hepatic disease from developing into cirrhosis clinically. PMID- 1421978 TI - [Effect of radix Salviae miltiorrhizae on calcium, zinc, copper content in serum, callus and bony tissue in early stage of healing process in rat closed tibial fracture]. AB - Changes of calcium, zinc, copper contents in serum, callus and bony tissue in the early stage of the healing process of rat closed tibial fracture, also the changes of them with radix Salviae miltiorrhizae (RSM) treatment were studied. It was found that calcium, zinc contents and Zn/Cu ratio increased significantly and the rise of serum copper content was inhibited by the administration of RSM after fracture. Zn/Cu ratio in fracture callus was correlated to the calcium content in fracture callus. These findings suggested that the effect of the promotion of RSM on fracture healing was related to the increased zinc content in serum, also related to the acceleration of mobilization of zinc in fractured bone, and to the acceleration of fracture callus formation and mineralization process by the increased zinc and Zn/Cu ratio in the callus of the fracture. PMID- 1421980 TI - [Experimental study of anisodamine on therapeutic effect of pulmonary edema in rats]. AB - The pulmonary edema (PE) induced by adrenaline (AD) is similar to neurogenic pulmonary edema. Anisodamine (654-2) showed an apparent therapeutic effect on it. The pulmonary wedge arterial pressure (PAWP), carotid arterial pressure (CAP) and blood gases were measured. It was found that in PE group, PAWP was increased to four-fold compared with those from before AD administration (from 0.98 +/- 0.24 to 4.04 +/- 0.53 kPa, mean +/- SD) rapidly. CAP was increased to one fold. The changes of PaO2,O2Sat and PaCO2 showed progressive hypoxia. The PaO2(kPa) was 11.0 +/- 1.3, 6.1 +/- 1.7, 4.4 +/- 1.9 and 3.8 +/- 1.9, PaCO2(kPa) was 4.1 +/- 2.1, 5.4 +/- 0.8, 9.7 +/- 2.9 and 10.3 +/- 3.4, O2 Sat(%) was 95.6 +/- 16.0, 69.2 +/- 15.1, 48.9 +/- 22.0, and 33.7 +/- 25.9 in order before AD injection, 1, 5 min after AD injection and before death respectively. Blood pH value also decreased in apparent way. All of animal died within 15 min. While in 654-2 therapeutic group, the significant increased PAWP and CAP were decreased gradually to normal within 30 min. The abnormal blood gases and pH were approached to repair within 20 min. All of animals survived. PMID- 1421981 TI - [In-depth research of the basic theory for the development of traditional Chinese medicine]. PMID- 1421982 TI - [Immunopharmacology of Angelica sinensis]. PMID- 1421983 TI - Limits to the criminal law in healthcare. PMID- 1421984 TI - Using humour as therapy in clinical practice. PMID- 1421985 TI - Suction therapy in the critically ill patient. AB - Caring for patients with inefficient airway function who need suctioning requires a great deal of nursing skill. This article outlines the methods of suction therapy currently available, the role of research in improving clinical practice and the way in which new technology may be used to benefit both patient and nurse. PMID- 1421986 TI - Minitracheostomy: the benefits for patient care. AB - Sputum retention is a potential complication following thoracic surgery. This article describes minitracheostomy, a technique that is commonly used in thoracic units to clear secretions, examines its advantages and disadvantages and recommends its more widespread use in district general hospitals. PMID- 1421987 TI - Caring for patients with enterocutaneous fistulae. AB - Fistulae are distressing for both patients and staff. The management of fistulae presents a challenge to the nurse in terms of providing care for the psychological and physiological needs of the patient. This article describes the causes of fistulae and examines the nursing priorities and how to achieve them. PMID- 1421988 TI - Caring for a homosexual man undergoing a colostomy formation. PMID- 1421989 TI - Implications of the theory/practice gap for Project 2000 students. AB - Nursing has frequently attempted to address the gap between theory and practice. This article explores their relationship and the implications of any theory/practice gap for emergent Project 2000 students. PMID- 1421990 TI - First aid: no longer an ephemeral feminine fashion. PMID- 1421991 TI - Rights to healthcare and the role of the nurse practitioner. AB - With the recent developments in healthcare now coming into effect, it is necessary to consider rights to healthcare, the balance of supply and demand and the role of the nurse practitioner as patient advocate. PMID- 1421992 TI - Career development in intensive care: 2. AB - In part 1 of this article, intensive care nursing and the career opportunities that are available were discussed. Part 2 will examine postregistration intensive care training and career progressions from grade D level to senior/specialist posts. PMID- 1421993 TI - Consumer satisfaction surveys in mental health. AB - Treating clients of mental health services as consumers is a relatively new concept in Britain. This article seeks to explain the development of consumer satisfaction surveys, reviews the literature, and identifies ways in which the approach can be used to improve services. PMID- 1421994 TI - Edema pattern of bones. Diagnosis and differential diagnosis in patients with knee pain. PMID- 1421995 TI - The evolution of post-traumatic osteoarthritis: its relationship to occult post traumatic subcortical fractures identified on MRI. PMID- 1421996 TI - MRI of the shoulder. AB - MR imaging of the shoulder has become an important imaging modality for that joint. Excellent soft tissue contrast and multiplanar acquisition provide optimal assessment of muscle, tendons, hyaline and fibrous cartilage, joint capsules, fat, bursae and bone marrow. The most common indications for shoulder MRI are suspected rotator cuff tear, shoulder instability, osteonecrosis, neoplasm and infection. In this article we describe MR technique, special anatomy of the shoulder, and diagnostic MR criteria of common pathologic conditions. PMID- 1421997 TI - [MRT of epiphyseolysis capitis femoris]. AB - MR imaging provides exact measurement of the epiphyseal angle by drawing a ventral tangent to the femoral neck in parasagittal images along the femoral neck. The average MR imaging angle was 49.7 degrees in SCFE. Important information is provided about the activity of the slipping process (reattachment) and the contralateral epiphysis. PMID- 1421998 TI - The lumbar spine: postoperative magnetic resonance imaging. AB - Persistent low back pain after surgery can be a severe diagnostic and therapeutic problem. By using MRI many causes of this failed back surgery syndrome (FBSS) can be disclosed. MRI is superior to other imaging modalities in this concern. In this article we describe the MR technique, normal and abnormal findings of the postoperative lumbar spine, such as persistent or recurrent disc herniation, epidural scar, spinal stenosis, pseudomeningocele, arachnoiditis, pseudarthrosis, hematoma, and infection. PMID- 1422000 TI - [MRT in osteomyelitis: detection of bone sequestration with Gd-DTPA]. AB - In 4/12 patients with subacute or chronic osteomyelitis MRI was able to detect bone sequestrae by use of gadolinium DTPA. This method is of great advantage in cases of infections not originating from osteosynthetic material. In patients in whom osteosynthetic material was removed completely, invisible metallic residuals may lead to signal deterioration. PMID- 1421999 TI - MRI of spondylitis. AB - MRI of proven spondylitis was performed in 39 patients. Acute spondylitis appeared hypointense on T1-weighted and hyperintense on T2-weighted images. Following intravenous administration of Gd-DTPA, enhancement of the marrow and disc was seen. With progressive healing an increasing signal was seen on T1 weighted images. This was caused by the presence of focal fat marrow representing the first sign of therapy response. As healing progressed, the T1-signal increased due to fatty marrow, while the T2-signal decreased as well as the enhancement following Gd-DTPA administration. Therefore, MR imaging can be recommended as the method of choice for early diagnosis of spondylitis and assessment of therapy response. PMID- 1422001 TI - MRI and MRS of the skeletal muscle. AB - Magnetic resonance imaging and spectroscopy were performed in several types of muscular disorders. In acute stages, 31P spectra showed remarkable changes compared with normals, and T2-weighted MR images were most sensitive in delineating the pathology. Fatty degeneration of muscle in chronic diseases yielded high contrast in T1-weighted MRI and could be quantified by 1H-MRS including the chemically selective determination of proton T1 values. In order to evaluate true abundance rations of phosphorus metabolites, 31P relaxation times T1 of muscle were measured by localized inversion recovery. PMID- 1422002 TI - [Digital documentation of image and findings]. PMID- 1422003 TI - DNA sequencing with chain-terminating inhibitors. 1977. PMID- 1422004 TI - Immunological screening method to detect specific translation products. 1978. PMID- 1422005 TI - Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. 1975. PMID- 1422006 TI - Detection of specific sequences among DNA fragments separated by gel electrophoresis. 1975. PMID- 1422007 TI - Use of synthetic oligonucleotides as hybridization probes: isolation of cloned cDNA sequences for human beta 2-microglobulin. 1981. PMID- 1422008 TI - Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. 1979. PMID- 1422009 TI - Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. 1977. PMID- 1422010 TI - Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. 1986. PMID- 1422011 TI - Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. 1987. PMID- 1422012 TI - A colony bank containing synthetic Col El hybrid plasmids representative of the entire E. coli genome. 1976. PMID- 1422013 TI - Construction of biologically functional bacterial plasmids in vitro. 1973. PMID- 1422014 TI - Cosmids: a type of plasmid gene-cloning vector that is packageable in vitro in bacteriophage lamda heads. 1978. PMID- 1422015 TI - Calcium-dependent bacteriophage DNA infection. 1970. PMID- 1422016 TI - A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. 1982. PMID- 1422017 TI - High-efficiency cloning of full-length cDNA. 1982. PMID- 1422018 TI - Construction of coliphage lambda charon vectors with BamH1 cloning sites. 1980. PMID- 1422019 TI - Insertion of a rabbit beta-globin gene sequence into an E. coli plasmid. 1975. PMID- 1422020 TI - Rat insulin genes: construction of plasmids containing the coding sequences. 1977. PMID- 1422021 TI - The use of RNAs complementary to specific mRNAs to regulate the expression of individual bacterial genes. 1984. PMID- 1422022 TI - A technique for expressing eukaryotic genes in bacteria. 1980. PMID- 1422024 TI - A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. 1983. PMID- 1422023 TI - Simple RNA enzymes with new and highly specific endoribonuclease activities. 1988. PMID- 1422025 TI - A further study of the T4 ligase-catalyzed joining of DNA at base-paired ends. 1972. PMID- 1422026 TI - A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes. 1985. PMID- 1422027 TI - Characterization of the human factor VIII gene. 1984. PMID- 1422028 TI - Human growth hormone: complementary DNA cloning and expression in bacteria. 1979. PMID- 1422029 TI - Synthesis in E. coli of a polypeptide with human leukocyte interferon activity. 1980. PMID- 1422030 TI - Structure and expression of a cloned cDNA for human interleukin-2. 1983. PMID- 1422031 TI - Molecular cloning of a cDNA encoding human antihaemophilic factor. 1984. PMID- 1422032 TI - A bacterial clone synthesizing proinsulin. 1978. PMID- 1422033 TI - Secretion of foreign proteins from Saccharomyces cerevisiae directed by alpha factor gene fusions. 1984. PMID- 1422035 TI - Transformation of yeast. 1978. PMID- 1422034 TI - Phenotypic expression in E. coli of a DNA sequence coding for mouse dihydrofolate reductase. 1978. PMID- 1422036 TI - Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host. 1984. PMID- 1422037 TI - Secretion of Escherichia coli beta-lactamase from Bacillus subtilis by the aid of alpha-amylase signal sequence. 1982. PMID- 1422038 TI - Isolation and purification of protein granules from Escherichia coli cells overproducing bovine growth hormone. 1985. PMID- 1422039 TI - Functional genetic expression of eukaryotic DNA in Escherichia coli. 1976. PMID- 1422040 TI - Bacteria mature preproinsulin to proinsulin. 1980. PMID- 1422041 TI - A chimaeric antibiotic resistance gene as a selectable marker for plant cell transformation. 1983. PMID- 1422042 TI - Propagation of foreign DNA in plants using cauliflower mosaic virus as vector. 1981. PMID- 1422043 TI - The Agrobacterium tumefaciens Ti plasmid as a host vector system for introducing foreign DNA in plant cells. 1980. PMID- 1422044 TI - Expression of chimaeric genes transferred into plant cells using a Ti-plasmid derived vector. 1983. PMID- 1422045 TI - Expression of Ti plasmid genes in monocotyledonous plants infected with Agrobacterium tumefaciens. 1984. PMID- 1422046 TI - High-velocity microprojectiles for delivering nucleic acids into living cells. 1987. PMID- 1422047 TI - Direct gene transfer to plants. 1984. PMID- 1422048 TI - Selective multiplication of dihydrofolate reductase genes in methotrexate resistant variants of cultured murine cells. 1978. PMID- 1422049 TI - Production of human tissue plasminogen activator in transgenic mouse milk. 1987. PMID- 1422050 TI - Dramatic growth of mice that develop from eggs microinjected with metallothionein growth hormone fusion genes. 1982. PMID- 1422051 TI - Production of human beta interferon in insect cells infected with a baculovirus expression vector. 1983. PMID- 1422052 TI - Transformation of mammalian cells with genes from prokaryotes and eukaryotes. 1979. PMID- 1422053 TI - Dystrophin: the protein product of the Duchene muscular dystrophy locus. 1987. PMID- 1422054 TI - Hypervariable 'minisatellite' regions in human DNA. 1985. PMID- 1422055 TI - Prenatal diagnosis of alpha-thalassemia clinical application of molecular hybridization. 1976. PMID- 1422056 TI - Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. 1985. PMID- 1422057 TI - Evolution of sickle variant gene. 1979. PMID- 1422058 TI - Synthesis of hepatitis B surface and core antigens in E. coli. 1981. PMID- 1422060 TI - Vaccinia virus: a selectable eukaryotic cloning and expression vector. 1982. PMID- 1422059 TI - Influenza antigenic determinants are expressed from haemagglutinin genes cloned in Escherichia coli. 1980. PMID- 1422061 TI - Human hepatitis B vaccine from recombinant yeast. 1984. PMID- 1422062 TI - Construction of poxviruses as cloning vectors: insertion of the thymidine kinase gene from herpes simplex virus into the DNA of infectious vaccinia virus. 1982. PMID- 1422063 TI - Protection from rabies by a vaccinia virus recombinant containing the rabies virus glycoprotein gene. 1984. PMID- 1422064 TI - Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. 1989. PMID- 1422065 TI - Continuous cultures of fused cells secreting antibody of predefined specificity. 1975. PMID- 1422066 TI - Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. 1989. PMID- 1422067 TI - Microorganisms having multiple compatible degradative energy-generating plasmids and preparation thereof. 1980. PMID- 1422068 TI - Process for producing biologically functional molecular chimeras. 1979. PMID- 1422069 TI - Transgenic non-human mammals. 1984. PMID- 1422070 TI - The intervening sequence RNA of Tetrahymena is an enzyme. 1986. PMID- 1422071 TI - DNA sequencing with Thermus acquaticus DNA polymerase and direct sequencing of polymerase chain reaction-amplified DNA. 1988. PMID- 1422072 TI - Site-specific mutagenesis using synthetic oligodeoxyribonucleotide primers: I. Optimum conditions and minimum oligodeoxyribonucleotide length. 1979. PMID- 1422073 TI - Synthesis of deoxyoligonucleotides on a polymer support. 1981. PMID- 1422074 TI - A new method for sequencing DNA. 1977. PMID- 1422075 TI - Atrial natriuretic peptide (ANP), aldosterone, angiotensin II and renin in the 'low T3 syndrome' in organ donors. AB - The present prospective study was conducted in order to investigate the effect of an acute decrease in serum T3 levels on ANP, aldosterone, angiotensin II, renin and ADH. All patients showed a pathologic TRH stimulation test prior to organ harvesting. Our patients developed secondary T3 hypothyroidism of different severity dependent on intensive care unit (ICU) stay. T3 values in group 1 (ICU stay > or = 77 h) were smaller than 70 ng/dl, those of group 2 (ICU stay < or = 53 h) were greater than 70 ng/dl. In both groups a severe elevation of plasma renin activity was measured, with almost high-normal values for ANP in group 1 and slightly elevated values in group 2 [not significant (n.s.)]. Results demonstrate that, contrary to patients who are not critically ill, brain-dead patients develop a dissociation of the renin-angiotensin-aldosterone mechanism. No statistical significant difference was found between the groups in serum levels of ADH and aldosterone. This endocrine dissociation, however, seems to have no clinical significance with regard to organ function after transplantation in kidney recipients. PMID- 1422076 TI - Application of an automated plasma filtration device and a blood monitoring system for LDL apheresis. AB - This study describes the adaptation of a filtration separation device (AK 10 from Gambro, Munchen, FRG) and a blood monitor system (BTS 100 from Diamed, Koln, FRG) to the automated adsorption/desorption device for LDL apheresis. Plasma separation by filtration was performed by a hollow-fiber filter (OP5, Asahi Corp., Japan). In order to evaluate the quality of the plasma obtained by filtration, the platelet contamination, the activity of factors V and VIII and the concentration of the immunoglobulins IgG and IgM were determined. The following results were found: Platelet contamination of the plasma was 2,740/microliters. As compared to the patient's pretreatment values, activity of factor V was 94%, activity of factor VIII was 104%, concentration of IgG was 96%, concentration of IgM was 94%. Ten LDL aphereses were evaluated: red cell counts, platelet counts, hemoglobin concentration and hematocrit were not changed significantly. Thus, this new combination system represents an improved alternative to previously performed centrifugation methods. PMID- 1422077 TI - Bedside monitoring of anti-coagulation under LDL apheresis by means of aPTT testing with a coagulation monitor. AB - Optimally adjusted anticoagulation under LDL apheresis is essential for successful treatment: Excessive anticoagulation exposes the outpatient to the risk of uncontrolled hemorrhage, insufficient anticoagulation may shorten the duration of utilization of the immune-adsorption columns. A new device (coagulation monitor 512, Ciba Corning) allows individual adaptation of dosage and timing of heparin application by modifying the standard schedule (5,000 IU intravenously before treatment, 2,000 IU/h continuously). APTT was measured before and after application of heparin and then at 30-min intervals both by the coagulation monitor and by conventional laboratory methods; the respective heparin concentration was determined in addition. The correlation coefficient between the heparin concentration and both the monitor-derived and the laboratory derived aPTT was 0.811 and 0.590, respectively. An explanation for this finding might be that the monitor avoids the influences induced by subsequent collection and testing of samples associated with laboratory procedures. PMID- 1422078 TI - [LDL cholesterol apheresis by adsorption to dextran sulfate]. AB - Extracorporeal LDL cholesterol elimination may be the sole successful treatment in familial hypercholesterolemia. By treatment of 41 plasma both total cholesterol and LDL cholesterol were lowered by 69 +/- 1% and 78 +/- 1%, respectively. HDL cholesterol was decreased by 24 +/- 3%. This could be explained both by hemodilution (hematocrit was decreased by 9.3 +/- 2.8%) and unspecific adsorption of various plasma proteins (-15.3 +/- 3.7 g/l, i.e. -22 +/- 4%). Protein electrophoresis showed different affinities of the protein fractions. These data suggest that LDL apheresis by dextran sulfate is an effective method for the elimination of LDL cholesterol. However, other proteins besides apolipoprotein B are adsorbed to dextran sulfate. PMID- 1422079 TI - Platelet loss during plasma exchange is unaffected by in-line filters. AB - 15 patients underwent plasma exchange using a standard 170-microns in-line filter with or without an additional 40-microns microaggregate filter in the return circuit. The mean platelet count fall immediately after plasma exchange in 15 patients was (54 +/- 6) x 10(9)/l and 48 h later was (23 +/- 8) x 10(9)/l representing a mean total platelet loss immediately after plasma exchange of (253 +/- 31) x 10(9) with no difference in the 40-microns filtered procedures. The mean platelet loss in the discarded plasma was (60 +/- 8) x 10(9), and a mean of 52 x 10(9) platelets were recovered from machine harness washings. The platelet loss in the removed plasma and in the harness therefore accounted for only 42-44% of the total loss of platelets. The inclusion of 40-microns microaggregate filters did not reduce platelet loss, and it is therefore unlikely that the thrombocytopenia is induced by reinfused microaggregates. It is likely that platelets are activated in the machine and sequestered in the spleen. PMID- 1422080 TI - The role of lipoproteins in the inactivation of endotoxin by serum. AB - The lipopolysaccharide (LPS)-induced release of cytokines from human monocytes can be prevented by previous interaction of serum with LPS. This inactivation is a function of lipoproteins. Here we show that LPS can be inactivated by low density lipoproteins (LDL) as well as by high-density lipoproteins (HDL). The effects of heparin and EDTA on LPS inactivation by serum are also described. PMID- 1422081 TI - Screening of blood donors and recipients for Borrelia burgdorferi antibodies: no evidence of B. burgdorferi infection transmitted by transfusion. AB - In the study presented here, the prevalence of antibodies against Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, was determined in a group of blood donors from the Wurzburg area (Southern Germany). 13 of 472 donors (2.7%) tested were positive by immunoblotting (IB). These 13 donors were examined in more detail by physical examination, anamnesis and determination of inflammation parameters of the blood. All persons were asymptomatic for Lyme borreliosis. One of 5 who remembered a tick bite actually had suffered from an erythema chronicum migrans 5 years ago. Another one had been affected by fever, headaches and pain in the limbs, arthralgia and motoric disorder in both hands 6 months before examination. Analysis of the blood did not provide any evidence of an acute infection. Moreover, each of the 472 serum samples was analyzed by a hemagglutination test (HAT). 26 (5.5%) showed a positive test result. In order to investigate whether a seroconversion of the recipients by transfusion of B. burgdorferi antibody-positive blood had taken place, 9 recipients of blood products originating from the 13 IB-positive donors were serologically reexamined. All samples taken proved to be antibody-negative. Consequently, the transfusion did not produce any seroconversion in the patients thus treated. PMID- 1422082 TI - [New possibilities in diagnosis of hemolytic diseases in newborns]. AB - The diagnosis and management of the hemolytic disease of the newborn (HDN) rely on measurement of maternal anti-D, amniotic fluid analysis, and fetal blood sampling by cordocentesis. However, amniocentesis and cordocentesis have substantial risks of fetomaternal hemorrhage and subsequent increase in maternal anti-D potency. In addition to quantitation, the functional activity of maternal anti-D has been determined by measuring the interaction of red blood cells sensitized by maternal serum in monocyte-monolayer assays. We assessed the functional activity of anti-D by titration of the sensitized red blood cells using selected sera with rheumatoid factor (RF) as human anti-IgG. First experiments using monoclonal anti-D showed a good correlation between erythrophagocytosis and RF titers. The bilirubin/protein ratio in amniotic fluid may be of great value in predicting the severity of HDN, as shown in 94 cases with severe and 39 cases with moderate disease. Amniotic fluid analysis is complicated by the presence of hemoglobin; we developed a computer program to solve this problem. To improve the serological diagnosis of ABO incompatibility, we measured IgG-anti-A,B in 1,392 maternal and newborn sera applying a sensitive gel test with Coombs serum. Furthermore, we determined the hemolytic activity of anti-A,B by microscopic observation of the morphological changes of red blood cells. PMID- 1422083 TI - Analysis of oligonucleotide binding, internalization, and intracellular trafficking utilizing a novel radiolabeled crosslinker. AB - Although antisense oligonucleotides have been widely used to inhibit gene expression, their mechanism of entry into cells and their site of action are still in some doubt. In this report, we describe a novel technique for kinetically analyzing oligonucleotide association with living cells as well as intracellular compartmentalization. The technique utilizes a photoactivatable, radiolabeled crosslinker, the Denny-Jaffe reagent. Oligonucleotides containing pendant amine groups were conjugated to this reagent, added to HL60 cells in culture, and photocrosslinked to associated proteins, which were analyzed electrophoretically. We find that several proteins are labeled, predominantly a 75 kD one that appears to be membrane-associated. Our results suggest that the majority of intracellular oligonucleotide is associated in vesicles with the same protein to which it bound on the cell surface, but only a small percentage of non protein-bound cytosolic oligonucleotide can be detected. Additionally, oligonucleotides are readily accumulated by nuclei, and by treating whole nuclei, a unique set of nuclear binding proteins is detected. PMID- 1422084 TI - Oligodeoxyribonucleotide phosphorothioate fluxes and localization in hematopoietic cells. AB - An antisense oligonucleotide phosphorothioate, previously shown to inhibit HIV-1 viral expression in chronically infected H9 cells, was fluorescently labeled to study oligonucleotide fluxes and localization within living cells. Observations based on flow cytometry and fluorescence microscopy show the following: within around 0.5-2 h, an apparent steady-state distribution of the oligonucleotide is achieved in which the intracellular oligonucleotide concentration is less than that present in the external medium; following oligonucleotide uptake and resuspension of the cells in oligonucleotide-free medium, an oligonucleotide efflux, with a time constant similar to that for uptake, is observed (although a significant fraction of the phosphorothioate remains within the cell); cellular uptake as a function of the external oligonucleotide concentration is nonlinear, being more efficient at lower concentrations (less than 2 microM); and a predominant oligonucleotide localization within the cell nucleus and perinuclear organelles is observed. PMID- 1422085 TI - Reversal of the malignant phenotype by an anti-ras ribozyme. AB - In this study a ribozyme (catalytic RNA) was designed to site specifically cleave the mRNA of the activated H-ras gene expressed in human bladder carcinoma EJ cells. The optimal conditions for catalytic cleavage by the ribozyme were demonstrated in vitro. A synthetic DNA encoding the ribozyme was cloned into a mammalian expression vector (pH beta APr-1) and transfected into EJ cells. The expressed ribozyme significantly altered the morphology and suppressed the growth of EJ cells in vitro. These cell lines were examined for their malignant potential in athymic (nude) mice by an orthotopic (transurethral) implantation model, which recapitulates the invasive potential of various bladder carcinomas. EJ tumors expressing the H-ras ribozyme were characterized by a marked reduction in tumor take and invasion compared to those formed by control EJ cells. These differences resulted in almost a twofold increase in survival of mice implanted with ribozyme-containing EJ cells. These results further elucidate the role of ras genes in tumorigenicity and invasion, as well as introduce ribozymes as a new class of anticancer agents. PMID- 1422086 TI - Lipofectin enhances cellular uptake of antisense DNA while inhibiting tumor cell growth. AB - A natural DNA oligomer (15-mer) was synthesized with a sequence complementary to the translation initiation codon region of the human TGF-alpha mRNA and mixed with Lipofectin to form unilamellar complexes. It was found that tumor cell growth was inhibited when HCT116 cells were treated with Lipofectin-DNA oligomer complexes or with Lipofectin alone. Uptake of 32P-labeled 15-mers into colon tumor cells was compared in the presence and absence of Lipofectin. The amount of labeled oligomer found in cells that received optimal ratios of Lipofectin to DNA was 4- to 10-fold higher than the amount found in cells that received 32P-labeled DNA alone. Although Lipofectin-antisense DNA oligomer treatment of HCT116 cells caused a dose-dependent inhibition of cell growth, there was a subsequent rise in target mRNA product. Because the mechanism of growth inhibition could not involve an inhibition of TGF-alpha expression, it was concluded that Lipofectin probably exerts a nonspecific, detergent-like effect upon the cell membrane, producing an enhancement of TGF-alpha processing and release. PMID- 1422087 TI - An indexed bibliography of antisense literature, 1991. PMID- 1422088 TI - Internal representations of movement in the cerebral cortex as revealed by the analysis of reaching. AB - Reaching movements have the well-defined goal of bringing the hand to the location of an object of interest. For neuroscientists a basic problem to be solved is how the nervous system transforms the visual information concerning the location of the object in space into a pattern of muscle activity necessary to bring the hand to it. According to Descartes, spirits passing from the eyes impinge on the pineal gland, causing it to lean in one direction or another; this leaning of the gland pulls on filaments (nerves) attached to the muscles. Modern treatments, instead, tend to decompose this process into sequences of transformations between informational representations. Such transformations lead from a description of the target in visual coordinates to an expression of the movement in muscle space by way of various internal representations. The organization of such internal representations has implications for the types of transformations actually performed in the brain. Recent psychophysical, neurophysiological, and computational approaches to study the cortical representations of reaching movements are yielding complementary data on this issue. PMID- 1422089 TI - Selective output-discriminative signals in the motor cortex of waking monkeys. AB - Monkeys and humans have similar capacities to discriminate between the frequencies of mechanical sinusoids delivered to the glabrous skin of their hands. Combined psychophysical-electrophysiological experiments in monkeys discriminating in the range of flutter provided evidence that this capacity depends upon differences in the cycle lengths in the sets of periodically entrained activity, evoked by the stimuli discriminated, in neurons of areas 3b and 1 of the (sensory) hemisphere opposite the stimulated hand. Identical experiments have now been made, in similarly trained and discriminating monkeys, in the motor cortex (area 4) of the hemisphere opposite the arm projecting selectively to one of two targets, to indicate discrimination (five hemispheres, 1137 neurons studied). We observed a selective signal of the upcoming correct discrimination in about 25% of the neurons of area 4 active in the task. The neuronal discharge occurs selectively for stimuli either lower or higher in frequency than that of the base stimulus, and commonly begins within 200-300 msec after onset of the comparison stimulus. These neuronal discharges are aperiodic, with no sign of the stimulus frequencies. EMG recording during performance of the discrimination showed that the muscles of the arm opposite the side of recording were silent during the period of stimulus presentations. Recordings during trials in which the animal made errors showed most commonly that the output of the discrimination operation was itself in error, followed by an appropriate arm projection to the wrong target. We interpret the selective response during the comparison stimulus to be a postdiscrimination signal projected transcallosally from the sensory hemisphere to the motor area of the hemisphere controlling the responding arm. We obtained no evidence that the discrimination operation is localized to any particular area, and we surmise it to occur in the dynamic activity within the distributed system linking the sensory cortex of one hemisphere and the motor cortex of the other. One-third of the neurons of the motor cortex responded to indentation of the skin of the ipsilateral hand, at trial onset. These responses varied from those closely linked to that sensory stimulus to those linked to the upcoming movement of the contralateral hand. These onset responses did not occur when similar sequences of mechanical stimuli were delivered to alert but idling monkeys. PMID- 1422090 TI - Reentry and the problem of integrating multiple cortical areas: simulation of dynamic integration in the visual system. AB - Studies of the cerebral cortex, particularly those of the visual system, demonstrate the existence of multiple, anatomically segregated and functionally specialized cortical areas. There is no evidence that these areas, which are linked by a network of reciprocal connections, are coordinated by a higher-order center. The visual image that we perceive, however, seems to be unified and coherent. In this article, we address the problem of integration posed by these observations. In an extension of our previous work, we develop a dynamic model of reentry. Reentry is a process of parallel and recursive signaling along ordered anatomical connections that achieves integration by giving rise to constructive and correlative properties within and among maps. We present and test a computer model simulating nine functionally segregated visual areas organized into three streams for form, color, and motion. The model receives visual input consisting of camera images of objects of different shapes and colors. We show the specialized response properties of the areas in the three streams. A computational strategy involving a phase variable is introduced to represent explicitly the dynamics of short-term temporal correlations among thousands of units distributed across different areas. We then illustrate constructive and correlative consequences of reentry within a system of reciprocal intra- and interareal connections by two examples taken from psychophysics: generation of form from motion and motion capture. The model solves the so-called "binding problem" through short-term correlations, which serve to link similar object features within a simulated cortical area and to bind multiple attributes of one or more objects across several areas, including a nontopographic one. Integration emerges from cooperative effects within and among the specialized areas. These effects lead to a simple output, a simulated foveation response, that is used as a basis for conditioning. Reward is mediated by the activation of a saliency system that is modeled on diffuse projection systems in the brain. As a result, the visual cortical model carries out foveation responses to input stimuli that require the dynamic conjunction and discrimination of form, color, and location for successful performance. PMID- 1422091 TI - Emergence of connectivity in the embryonic rat parietal cortex. AB - In order to understand how cortical circuitry is put together, we examined the emergence of corticofugal projection cells and the arrival of subcortical afferents in the presumptive parietal cortex of the embryonic rat cerebrum. Afferent and efferent projections were selectively labeled by applications of the lipophilic tracers DiI and DiA in aldehyde-fixed brains of 12-18-d-old rat embryos (E12-E18; gestation: 21 d). On E12 and E13, the neocortical anlage consists of a ventricular zone and a preplate, with no extracortical connections. By E14, just prior to the appearance of the cortical plate, polymorphic cells located in the ventrolateral preplate of the telencephalic vesicle send out the first group of corticofugal axons toward the ganglionic eminence. Shortly thereafter, the cortical plate emerges as a dense band of radially oriented cells that also contribute to the corticofugal projection. By E15, axons of the early cortical projection cells cascade through the striatal primordium, the future site of the internal capsule. At the time of cortical plate formation and initial corticofugal axon outgrowth, ascending corticopetal axon systems have not yet arrived in the neocortex. Double-labeling experiments in which one dye is placed in the neocortex and the other in the ipsilateral dorsal thalamus reveal that cortical efferents encounter the first ascending wave of thalamofugal axons at the level of the striatum. Collectively, these two axonal systems bridge the necortex and the diencephalon. Upon their arrival in the neocortex on E16, thalamic axons follow a ventrolateral to dorsomedial course within the intermediate zone. Thalamic axons are the first subcortical afferent system to arrive in the neocortex. Other ascending afferent systems arising from the midbrain tegmentum enter the neocortex after E17. Comparison of thalamocortical and tegmentocortical projections in two halves of the same brain and across various embryonic ages clearly reveals that the two projection systems differ in their trajectories as well as in their time of arrival. Present observations challenge the view that the precocious arrival of subcortical axons provides the impetus for cortical maturation, and suggest that cortical plate differentiation and the initial organization of corticofugal projection patterns occur independent of ascending pathways. PMID- 1422092 TI - Varieties of functional deficits in prosopagnosia. AB - Prosopagnosia is a neurologically based deficit characterized by the inability to recognize faces of known individuals in the absence of severe intellectual, perceptual, and memory impairments. The nature of the underlying disturbance was investigated in three patients in an attempt to identify the structural and functional levels at which the processing of faces breaks down, the relation between prosopagnosia and associated deficits, and the specificity of the prosopagnosic disturbance. The breakdown of face processing resulted from unilateral damage in different cerebral structures of the right hemisphere in the three patients, and it involved different functional levels of face processing, but all three patients displayed perceptual impairments of unequal severity. In one patient (R.M.), the deficit encompassed all perceptual operations on faces, including matching identical views of the same faces, but it did not extend to all categories of objects characterized by a close similarity among their instances; the second patient (P.M.) exhibited a less severe perceptual impairment but was unable to derive the configurational properties from a facial representation and to extract its physiognomic invariants; the third patient (P.C.) had not lost the capacity to differentiate faces on the basis of their configurations but could not associate a facial representation with its pertinent memories. Associated deficits were present in each patient but differed depending on the anatomofunctional locus of the breakdown, although all patients were impaired at recognizing noncanonical views of objects that they readily recognized when shown from a conventional viewpoint. However, performance dissociation within patients and double dissociation between patients suggest that these associated deficits are not necessary concomitants of prosopagnosia. PMID- 1422093 TI - Implicit access to knowledge derived from unrecognized faces in prosopagnosia. AB - Prosopagnosia is an acquired neurological impairment characterized by an inability to experience a feeling of familiarity at the view of faces of known individuals and to identify these individuals. The inability of prosopagnosic patients to recognize faces does not entail that perceived faces go unprocessed in their brains, and there are indications that cognitive operations are still performed whereby a perceived face reactivates pertinent memories, but either these operations cannot be completed or their outcome fails to reach consciousness. A series of experiments were conducted on three severe prosopagnosic patients in an attempt to understand better this phenomenon known as covert face recognition, the conditions for its occurrence, and its functional locus. The capacity of the patients implicitly to access pertinent knowledge related to overtly unrecognized faces was inversely related to the severity of their perceptual deficit, suggesting that some preserved ability to extract the physiognomic invariants of a face is a necessary condition for the occurrence of the phenomenon. However, the results indicated that covert recognition does not take place at a perceptual or structural level although it is initiated at such a level, that it may have more than one underlying mechanism, and that it is achieved through the reactivation of specific information related to the individual's identity. Under special conditions that restricted the relevant knowledge that needed to be activated, transient overt recognition of faces was experienced by one of the prosopagnosic patients. PMID- 1422095 TI - Multiplicity of inputs in the afferent path to cat auditory cortex neurons revealed by tone-on-tone masking. AB - This report presents preliminary evidence on the effect of continuous tonal maskers on the responses of single primary auditory cortical neurons in anesthetized cats to tonal signals across their effective frequency ranges 10 dB above characteristic frequency threshold. Tonal maskers had three kinds of effects. In many cells, the masker produced a generalized suppression of responses to tones across the response area. In some neurons, typically those with monotonic intensity profiles, tonal maskers on one side of the response area produced a selective suppression of responses to tone signals on the same side as the masker. This differential sensitivity to the masker is evidence of independent inputs to those neurons on the high- and low-frequency sides of their excitatory response areas. Finally, in non-monotonic neurons, tonal maskers at the high-frequency edge of the excitatory response area produced enhanced responses to tonal signals on the same side of the response area as the masker. We interpret this as a release from the effect of an inhibitory input located at the high-frequency edge of the response area. PMID- 1422094 TI - In vivo myeloarchitectonic analysis of human striate and extrastriate cortex using magnetic resonance imaging. AB - A primary goal of investigations into the organization of human cerebral cortex is to determine the functional specificity of architectonic regions. This includes the correlation of neurobehavioral deficits with neuropathological data for clinical diagnosis and treatment, and the identification of active brain regions using functional neural imaging techniques, such as positron emission tomography, electroencephalographic and magnetoencephalographic (EEG and MEG) source localization algorithms, and direct cortical stimulation. Currently, the architectonic classification of a cortical region identified by these methods is inferred from the comparison of its cerebral topographic position to cytoarchitectonic brain atlases. However, substantial intersubject variability in the position of cytoarchitectonic regions with respect to cerebral topographic landmarks may lead to errors in this procedure. An alternative method is presented here, which uses magnetic resonance (MR) imaging to identify myeloarchitectonic regions of isocortex directly by estimating the relative concentration of myelin within cortical laminae. This high-resolution MR protocol is used to identify striate cortex (Brodmann's area 17) and extrastriate cortex in vivo. Correspondence of MR signal intensity with myeloarchitectonic data from a postmortem brain confirms this identification. As MR imaging technology improves, this noninvasive method has the potential to identify and discriminate among at least 50 cortical regions in the living human brain. PMID- 1422096 TI - Increased gut parasympathetic activity and chronic diarrhoea in a patient with the acquired immunodeficiency syndrome. AB - A 25-year-old homosexual man with a 2-year history of watery diarrhoea and a 20 kg weight loss is described. He had been diagnosed HIV-1 antibody positive 6 years previously. Investigations excluded opportunist pathogens and other known causes of diarrhoea. A range of anti-diarrhoeal medication had been unsuccessful. Plasma levels of gastrointestinal and pancreatic peptides were normal and treatment with the somatostatin analogue, octreotide, which inhibits release of pancreatic/gut peptides, did not provide any benefit. Cardiovascular autonomic function tests revealed blunted pressor responses but no other abnormalities. Gastric emptying studies with a technetium labelled meal indicated rapid gastric emptying time. This was slowed by the anticholinergic drug, atropine. This suggested increased parasympathetic activity to the gut. He was, therefore, treated with the anti-cholinergic agent, propantheline bromide, which reduced the frequency and volume of stools. He put on weight and has remained well since. This case highlights the diagnostic challenge in HIV-associated chronic diarrhoea, the case for investigations of autonomic function, and the need for a therapeutic trial of anticholinergic drugs, when other measures have failed. PMID- 1422097 TI - Effects of plasmapheresis on short-term variability of blood pressure in healthy donors. AB - The acute effect of mild central hypovolaemia induced by plasmapheresis on the short-term variability of blood pressure and heart rate was evaluated in ten healthy donors. Indirect finger blood pressure was measured by a non-invasive device (Finapres). Analogue-to-digital conversion of the blood pressure was used to determine systolic, diastolic and mean blood pressure and heart rate every second. The equidistant sampling allowed a direct spectral analysis using a fast Fourier transform algorithm. Blood pressure and heart rate were maintained while an increased overall variability of blood pressure was observed after plasmapheresis. The increased total area under the curve of the systolic and diastolic blood pressure spectra was documented with the selective analysis of the three main components of the spectra: the increase in the oscillations of blood pressure following plasmapheresis predominated in the 66-129 mHz region, corresponding to Mayer waves. The spectral profile of HR was unaffected by plasmapheresis. The significant increase in the 10-s period oscillations of blood pressure after the mild central hypovolaemia could result from the unloading of cardiopulmonary (and arterial) baroreceptors which in turn could buffer the arterial pressure through sympathetic activation, detected on the systolic and diastolic pressure spectra in the low-frequency range. PMID- 1422098 TI - Elevation of plasma atrial natriuretic peptide occurs during adrenaline infusion in hypertensive but not normotensive subjects. AB - The levels of plasma atrial natriuretic peptide in response to graded adrenaline infusion were determined in six patients with essential hypertension and six healthy normotensive subjects (controls). Basal plasma adrenaline concentration was similar in both groups and rose progressively and to a similar level during adrenaline infusion. Plasma noradrenaline rose in both groups and to the same extent during the 26 and 39 ng/kg/min adrenaline infusion rates. Basal plasma atrial natriuretic peptide levels were higher in the hypertensives than in the controls. Graded adrenaline infusion had no effect on atrial natriuretic peptide levels in the controls but significantly raised atrial natriuretic peptide levels in the hypertensives. Systolic blood pressure rose progressively during adrenaline infusion at a lower infusion rate in the hypertensives than in the controls. Similarly, while heart rate rose during adrenaline infusion in both groups, there was a greater rise in the hypertensives. The increased cardiovascular responsiveness to adrenaline infusion in patients with essential hypertension may explain why plasma atrial natriuretic peptide levels rose only in this group and not the normotensive subjects. PMID- 1422100 TI - Time-frequency dynamics in neurally mediated syncope. AB - In this study, the responses during syncope were determined by noninvasive beat to-beat analysis during passive orthostasis. Twenty patients with recurrent unexplained syncope (13 men and seven women) and ten healthy aged-matched control subjects were studied during 80 degrees head-up tilt for 25 min. Time-frequency mapping of R-R intervals, systolic and diastolic pressures and respiration was used to determine the responses to tilt. The spectral estimation was based on a modified Wigner distribution and the frequency content was evaluated on a beat-to beat basis. Ten patients developed syncope (tilt-positive group) during tilt, while the remaining ten were asymptomatic (tilt-negative group). Control subjects reacted to tilt by the immediate shortening of R-R intervals to a plateau with an accompanying moderate increase in diastolic pressure. In the tilt-negative group the responses to tilt were similar, but of greater amplitude. In contrast, in the tilt-positive group, R-R intervals gradually and continuously decreased with tilt while systolic and diastolic pressures increased until shortly before syncope, when an abrupt fall in blood pressure followed by R-R intervals lengthening occurred. Furthermore, the R-R intervals fluctuations at both respiratory and nonrespiratory frequencies were the highest at rest as well as during tilt in the tilt-positive group. Nonrespiratory fluctuations in blood pressure increased more during tilt in both tilt-positive and negative groups compared to the control group. The nonrespiratory fluctuations in R-R intervals and blood pressure reached a maximum at syncope, simultaneously with hypotension and bradycardia. Time-frequency mapping has demonstrated that an elevated parasympathetic tone at rest which persists during orthostasis identifies patients prone to vasodepressor syncope. The counteracting sympathetic activation is not sustained and results in hypotension followed by cardioinhibition and loss of consciousness. PMID- 1422099 TI - Autonomic responses to carbohydrate ingestion and head-up tilt in elderly subjects with orthostatic hypotension. AB - To investigate the role of glucose and insulin in the development of hypotension following glucose ingestion in elderly subjects with orthostatic hypotension, the autonomic responses to glucose and xylose ingestion were studied in five elderly subjects with age related orthostatic hypotension (without autonomic failure), five elderly control subjects and three elderly subjects with evidence of autonomic failure. Heart rate, blood pressure, plasma noradrenaline and plasma arginine vasopressin responses to glucose ingestion and to xylose ingestion were investigated. All subjects were supine for 90 min following ingestion of each carbohydrate and were then tilted 45 degrees head-up for 10 min. Blood pressure was maintained in elderly control subjects following ingestion of both carbohydrates and during tilting. The elderly group with orthostatic hypotension, while supine had a fall in systolic blood pressure 60-90 min following both glucose and xylose ingestion. Diastolic blood pressure was lowered 60-90 min after glucose but not xylose. During tilting, blood pressure fell by similar levels following both carbohydrate ingestions; plasma noradrenaline levels after 2 min and plasma arginine vasopressin levels after 10 min tilting were significantly less following glucose ingestion compared to xylose ingestion. The autonomic failure group while supine had a fall in systolic blood pressure 60-90 min following both glucose and xylose ingestion. Diastolic blood pressure was lowered 60-90 min after glucose but not xylose. During tilting, blood pressure fell by similar levels following both carbohydrate ingestion. Plasma noradrenaline and arginine vasopressin levels were unchanged after ingestion of either carbohydrate, and during tilting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422101 TI - Portable infrared pupillometry using Pupilscan: relation to somatic and autonomic nerve function in diabetes mellitus. AB - The relationship between dynamic pupillary function and peripheral nerve function was studied in 85 randomly-selected diabetic patients and 67 age-matched normals using a portable infrared pupillometer (Pupilscan Version 5). Seven measurements were chosen to represent different components of the pupillary constriction redilatation curve after a standardized light stimulus. Constriction latency was significantly prolonged in diabetic patients (p = 0.05), as was time to 63% redilatation (p = 0.001). Thermal thresholds at the feet weakly correlated with relative reflex amplitude (warm: r = -0.22, p = 0.05; cool: r = -0.23, p = 0.05), but vibration perception thresholds were more strongly associated with constriction and redilatation velocity (r = -0.42, p = 0.001; r = -0.28, p = 0.03). Among the cardiovascular autonomic function tests, only respiratory R-R variation correlated with constriction velocity (r = 0.47, p < 0.001), and Valsalva ratio with redilatation velocity (r = 0.25, p = 0.04), but postural systolic blood pressure change was also correlated with reflex amplitude and latency time (r = -0.42, p < 0.001; r = 0.41, p = 0.001). There were no significant associations with three measures of sweating function in the feet. Pupil measurements were abnormal in 4-11% of diabetic patients, while other neurological tests were abnormal in 8-35%, consistent with the length-dependence of diabetic neuropathy. Median coefficients of variation were 2.0-7.2% in diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422102 TI - Suprasensitivity to calcitonin gene-related peptide but not vasoactive intestinal peptide in women with chronic pelvic pain. AB - Chronic pelvic pain in women is associated with radiological evidence of pelvic venous dilatation and reduced flow, termed 'pelvic congestion'. The aim of this study was to elucidate a possible role in this condition for vasoactive intestinal peptide and calcitonin gene-related peptide, both localized in perivascular nerves in the ovaries and uterus. Healthy volunteers and women with chronic pelvic pain and venous congestion received intravenous infusions of vasoactive intestinal peptide (n = 15), calcitonin gene-related peptide (n = 15) or a bland infusate (n = 7). Changes in the uterovaginal and skin blood flow were assessed by continuous measurement of vaginal, axillary, cheek and hand temperature. During calcitonin gene-related peptide infusion median hand temperature changes were +0.97 degrees C in women with pelvic pain and -0.03 degrees C in healthy volunteers (p < 0.05). There were no differences between groups in hand and cheek temperature responses to vasoactive intestinal peptide infusion. Vasoactive intestinal peptide and calcitonin gene-related peptide appeared to dilate the uterovaginal vasculature in healthy subjects but not in those with pelvic pain. Vasoactive intestinal peptide and calcitonin gene-related peptide did not provoke pain in healthy subjects but in those with pelvic pain, symptoms were significantly exacerbated during calcitonin gene-related peptide infusion but not by vasoactive intestinal peptide. Changes in plasma follicle stimulating hormone, luteinizing hormone and oestradiol during either infusion were not significant. These findings indicate greater sensitivity to calcitonin gene-related peptide in women with pelvic pain and suggest a possible underlying neurovascular disorder. PMID- 1422103 TI - Endoscopic transthoracic sympathectomy for idiopathic upper limb hyperhidrosis. AB - A 5-year experience of 51 endoscopic transthoracic dorsal sympathectomies for idiopathic palmar hyperhidrosis in 26 patients is presented. Fifty-two percent complained of excessive sweating over their hands, 28% of axillary sweating and 20% over both areas, with a mean duration of 10 years. The second, third and fourth thoracic ganglia and their interconnecting fibres on the affected side were ablated using diathermy cautery. Over a mean follow up time of 26 months, this procedure was successful in curing or improving intractable sweating in 92%. However, axillary sweating was less well controlled than in the palms with 20% of patients describing residual wetness in the axilla. Compensatory sweating (75%) and gustatory sweating (48%) were the commonest side effects; despite this, most patients were satisfied with the functional and cosmetic outcome. Other complications included a temporary Horner's syndrome in one patient, a pneumothorax in the immediate post-operative period in another and a unilateral non-infective reactionary pleural effusion in a third. Two patients developed recurrence of palmar hyperhidrosis within 6 months of surgery. One has been successfully treated by re-operation on the affected side. All patients complained of mild to moderate interscapular chest pain which was easily controlled by non-steroidal anti-inflammatory agents, and resolved within 7-10 days post-operatively. The technique of endoscope transthoracic sympathectomy is effective, relatively simple to perform and usually requires only an overnight stay. It is recommended as the surgical treatment of choice for upper limb hyperhidrosis unresponsive to conservative measures. PMID- 1422104 TI - Temazepam misuse in a group of injecting drug users. AB - It is well recognized that many injecting drug users are poly-drug users. The intravenous use of Temazepam has become popular recently. In response to the ease of misuse, the pharmaceutical industry produced a formulation that would be as 'resistant' as possible to injecting. The preparation is a gel-filled formulation, one proprietary name being Temazepam Gelthix. General Practitioners have been encouraged to prescribe gel-filled capsules to potential drug misusers in order to reduce the harm Temazepam can cause by its misuse. This study of 23 Temazepam injectors shows that the group still find the gel-filled preparation readily injectable. It appears to be more problematic in causing medical complications including superficial thrombophlebitis, abscesses and deep venous thrombosis. Temazepam misuse can cause drug users to become more chaotic. The study group recognize this and suggest there should be stricter control on the supply of Temazepam to drug dependents. General Practitioners, who are the main source of Temazepam prescribing, require additional training in prescribing to drug users. PMID- 1422105 TI - The prices of alcoholic beverages in the Nordic countries. AB - Apart from Denmark, all the Nordic countries have state-owned monopolies which handle all of the off-premise retail sales of wine and spirits. In some of the countries, the state monopoly also distributes strong and medium-strong beer. This paper discusses how the prices of beer, wine and spirits are set in the Nordic countries and compares the setting of prices in each. The paper shows that there are great differences both between the prices of alcoholic beverages in the Nordic countries and between the price-fixing mechanisms. The main part of the price differential is due to differences in taxation, but substantial discrepancies still exist when we look at prices exclusive of alcohol taxes. The reason for this is to be found in differences in profits and in the efficiency of producing and distributing alcoholic beverages. According to our data, it seems that some of the state monopolies are more effective than firms in the Danish market. PMID- 1422106 TI - Legislating responsible alcohol service: an inside view of the new Liquor Licence Act of Ontario. AB - The Ontario Government has recently passed a new Liquor Licence Act, based on the recommendations of a special advisory committee. This paper describes how the advisory committee framed the issues and arrived at a lengthy document detailing 73 recommendations on issues such as licence classification, the control of special permit functions, days and hours of operation, legal drinking age, alcohol advertising, the civil liabilities of alcohol providers and server training. The key actors and considerations are discussed, as well as the subsequent Cabinet action on the report and the implementation process currently underway. The paper concludes with an assessment from both an administrative and a public health perspective, with particular attention to the limited role which research played in these policy decisions. PMID- 1422107 TI - The difference context makes: Americans' views on abstinence and impairment. AB - While it is acknowledged that social norms play a role in determining acceptable drinking levels, there has been little research on the factors that determine approved or prohibited consumption levels in particular social contexts. This paper investigates the factors that influence the choice of abstention or impairment (as compared to 'social drinking') through an analysis of the 1984 survey of American drinking patterns using logistic regression, a method that allows the separate identification of social and demographic factors that encourage abstention or impairment. Results show that although the effects of drinking status variables (such as lifelong abstainer) are contextually neutral, most social and demographic characteristics have differential effects depending on the specific context and the choice of abstention or impairment. PMID- 1422108 TI - Tobacco smoking in Moscow school students. AB - A cross-sectional study on tobacco smoking prevalence and related socio psychological parameters in Moscow school students aged 10-17 was performed. Data from an anonymous self-report (n = 4802) on smoking prevalence was confirmed by special technique--expert assessment. Widespread smoking was found: among male 5th graders (the youngest group) 14.4% are smokers (those who smoked at least 1 cigarette over the past 3 months); among male 10th graders (oldest group) 53.2% smoke; among females these figures were 0.8% for the youngest students and 28.2% for the oldest ones. A significant difference in awareness of smoking health hazards and attitudes towards the habit was shown among school students with various smoking statuses. Complaints about cough and shortness of breath after light physical stress were significantly more prevalent in regular smokers as compared to non-smokers. The possible causal role of some psychological factors in early formation of smoking habit is discussed. PMID- 1422109 TI - Alcohol placebos: you can only fool some of the people all of the time. AB - Some data from three studies of the acute psychological effects of alcohol are presented. After blind administration subjects could often tell that they had consumed alcohol, presumably because of its physiological effects. About 50% of subjects who received placebo alcohol felt slightly drunk and guessed that they had received alcohol. But, subjects who had actually received alcohol rated themselves as more drunk and were much more likely to guess that they had received alcohol. Subjects could also approximately estimate how much alcohol they had drunk. These findings suggest that the effects of unblinding should be considered when alcohol is administered in placebo designs. True blind placebo administration may only be possible when achieved BAL is < 40 mg/100 ml. PMID- 1422110 TI - The prevalence of illicit drug use in six metropolitan areas in the United States: results from the 1991 National Household Survey on Drug Abuse. AB - National levels and trends of illicit drug use in the general population are well documented. However, little is known about how this phenomenon is distributed among various subnational areas such as state, metropolitan area, and other local areas. The sample design from the National Household Survey on Drug Abuse (NHSDA) was recently expanded such that estimates from several large metropolitan areas could be produced with reasonable precision. The prevalence of illicit drug use is examined in six large metropolitan areas of the United States. These findings indicate that, in some cases, drug use varies considerably by metropolitan area. PMID- 1422111 TI - Opiate treatment for drug users: an incomplete picture. (Reply to letter appearing in the BJA (1991) 86, pp. 1355-1356) PMID- 1422112 TI - Alcohol placebos: you can only fool some of the people some of the time. PMID- 1422114 TI - Reconstituting animals from immortal precursors. AB - Several recent experiments have shown that immortal neural and muscle cells retain the specific temporal and spatial properties of their precursor cells in the animal. In addition, the immortal cells retain the ability to differentiate in vitro and, after transplantation, in vivo. The results of these experiments suggest that the use of precursor cell lines may lead to powerful approaches for understanding the mechanisms that generate the ordered distribution of cell types in mammals. PMID- 1422113 TI - Schwann cells: early lineage, regulation of proliferation and control of myelin formation. AB - This article reviews selected topics of particular relevance for understanding the process of Schwann cell development. It will discuss early commitment to the Schwann cell lineage and Schwann cell precursors, regulation of Schwann cell proliferation, and regulation of myelin formation. PMID- 1422115 TI - Cell adhesion molecules, second messengers and axonal growth. AB - Recent studies on NCAM-related molecules suggest that individual cell adhesion molecules might function to both promote axonal growth during development and maintain synaptic structure in the adult. Evidence that differential alternative splicing contributes to this apparent bifunctionality of cell adhesion molecules is discussed. PMID- 1422116 TI - Neuronal polarity. AB - The axonal and somatodendritic domains of neurons differ in their cytoskeletal and membrane composition, complement of organelles, and capacity for macromolecular synthesis. Recently there has been progress in elucidating the cellular mechanisms that underlie the establishment and maintenance of neuronal polarity, including microtubule organization and the sorting, transport, and anchoring of membrane proteins. PMID- 1422118 TI - Neuronal cytoskeleton and growth. AB - The involvement of the cytoskeleton in the expression of neuronal morphology is most obvious in its support of neurite extension and the motile activity of growth cones. Techniques permitting direct observation of the dynamics of proteins in living cells, along with attempts to assay protein function in vivo, are testing existing models for cytoskeletal function in neurons, as well as generating more detailed models at the molecular level. PMID- 1422117 TI - Membrane trafficking in neurons. AB - Neurons possess an unusually extensive Golgi apparatus and exhibit a variety of active endocytic-like processes. The Golgi apparatus and the endocytic phenomena both contribute, probably in multiple overlapping ways, to the genesis and fate of the membrane systems in axons and terminals. PMID- 1422119 TI - Phototransduction in Drosophila: a paradigm for the genetic dissection of sensory transduction cascades. AB - A combination of molecular, genetic and physiological studies is providing fundamental insight into the function and regulation of the phototransduction cascade. The availability of Drosophila mutants with defects in visual physiology allows for an in vivo dissection of this complex sensory signal transduction process. PMID- 1422120 TI - Natural and experimental prion diseases of humans and animals. AB - Prions cause transmissible and genetic neurodegenerative diseases. Infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrPSc), which is encoded by a chromosomal gene. Although the PrP gene is single copy, transgenic mice with both alleles of the PrP gene ablated develop normally. A post-translational process, as yet unidentified, converts the cellular prion protein (PrPC) into PrPSc. Scrapie incubation times, neuropathology and prion synthesis in transgenic mice are controlled by the PrP gene. Mutations in this gene are genetically linked to the development of neurodegeneration. Transgenic mice expressing mutant PrP spontaneously develop neurological dysfunction and spongiform neuropathology. Future investigations of prion diseases using molecular biological and genetic approaches promise to yield much new information about these once enigmatic disorders. PMID- 1422121 TI - Amyloidogenesis in Alzheimer's disease: basic biology and animal models. AB - A principal neuropathological hallmark of Alzheimer's disease is deposition of beta-amyloid, composed primarily of a 4 kD peptide, A beta. This peptide is derived from larger amyloid precursor proteins. The mechanisms that are responsible for A beta formation in vivo are unknown. Recently, transgenic strategies have been employed to test several hypothetical mechanisms in order to reproduce Alzheimer's disease-specific pathology in rodents. PMID- 1422122 TI - The disordered neuronal cytoskeleton in Alzheimer's disease. AB - Evidence continues to accrue in support of the notion that normal adult human tau is converted into the protein subunits of Alzheimer's disease paired helical filaments as a result of the abnormal phosphorylation of tau at aberrant sites. Although the biological consequences of the generation of these abnormal tau derivatives in neurons remain uncertain, it is plausible that this process could destabilize microtubules and have a deleterious effect on the function and survival of neurons. Recent studies that probe the mechanisms whereby normal tau, a component of the neuronal cytoskeleton, undergoes profound alterations to become paired helical filaments in the Alzheimer's diseased brain are discussed. PMID- 1422123 TI - Role of excitotoxicity in human neurological disease. AB - An increasing body of evidence has implicated excitoxicity as a mechanism of neuronal death in both acute and chronic neurological diseases. A major recent advance has been the successful cloning and expression of the non-NMDA, NMDA, and metabotropic glutamate receptors. The cellular mechanisms responsible for cell death following activation of these receptors are still being clarified. A recent advance in conceptualizing excitotoxicity is the notion that a slow excitotoxic process may occur as a consequence of either a receptor abnormality or an impairment of energy metabolism. It is possible that such a mechanism may occur in neurodegenerative illnesses. Recent therapeutic studies have focused on glycine site antagonists and on the efficacy of non-NMDA antagonists in ischemia. PMID- 1422124 TI - Cytokines in neural regeneration. AB - Growth factors with already established multiple effects on non-neural cells continue to be of considerable interest to researchers with regard to the nervous system, where regulation of cell maintenance and plasticity in relation to lesion and regeneration is part of their functional repertoire. Fibroblast growth factors, interleukins, and type beta transforming growth factors are prominent representatives of such proteins. Ciliary neurotrophic factor is another multifunctional neurokine. The proposed role of this molecule as a 'lesion factor', however, is still not firmly settled. PMID- 1422125 TI - Macrophages and nerve regeneration. AB - Macrophages are not only phagocytic cells but also secrete a plethora of growth factors that are potentially important for regeneration. This review will examine the emerging evidence of a likely contribution by macrophages to axonal regeneration. PMID- 1422126 TI - Dopaminergic transplants in experimental parkinsonism: cellular mechanisms of graft-induced functional recovery. AB - The ability of intrastriatal grafts of fetal mesencephalic dopamine neurons to ameliorate the symptoms of experimental and clinical parkinsonism has raised the question of the mechanisms underlying the transplant-induced functional effects. Recent studies have taken advantage of quantitative cytochemical and in situ hybridization techniques to study functional graft-host interactions at the cellular level in the rat Parkinson model. The results provide evidence that behaviorally functional grafts restore dopaminergic neurotransmission and normalize dopamine receptor function in the denervated striatum, and that these effects are likely to depend on both synaptic and extrasynaptic mechanisms. PMID- 1422128 TI - Disease, transplantation and regeneration. PMID- 1422127 TI - Neuronal and glial cell biology. PMID- 1422129 TI - Ganglioside GM1 and sphingolipid breakdown products in cellular proliferation and signal transduction pathways. PMID- 1422130 TI - Synthesis of O-glycopyranosyl-N-hydroxysuccinimides of glucose and lactose and their opening by nucleophiles into prespacer glycosides. AB - O-Glycopyranosyl-N-hydroxysuccinimides of glucose and lactose have been synthesized. Peracetylated sugars, acetobromo sugars and benzoylated thioethyl glycosides have been used as precursors. With boron trifluoride etherate in dichloromethane, peracetylated sugars gave predominantly the beta anomer. Trimethylsilyl trifluoromethanesulfonate in nitromethane, however, gave predominantly the alpha anomer. Treatment of the acetylated O-glucopyranosyl-N hydroxysuccinimide with various nucleophiles (methoxide, hydroxide and pentylamine) gave the corresponding deacetylated N (succinyl)glucopyranosylhydroxylamines in almost quantitative yield. These derivatives are suitable for the formation of glycoconjugates or attachment of carbohydrates to solid phases using the opened succinimide as linking arm. PMID- 1422131 TI - Determination of sequence and linkage of tissue oligosaccharides in caprine beta mannosidosis by fast atom bombardment, collisionally activated dissociation tandem mass spectrometry. AB - Fast atom bombardment, collisionally activated dissociation tandem mass spectrometry (FAB-CAD-MS/MS), combined with p-aminobenzoic acid ethyl ester (ABEE) derivatization, were used to confirm the sequence and linkage pattern of subnanomolar amounts of the previously characterized three major thyroid gland oligosaccharides accumulated in caprine beta-mannosidosis. Positive ion FAB-CAD MS/MS of both the [M + H]+ and [M + Na]+ ions from the ABEE derivatized oligosaccharides produced product ions derived from cleavage of the glycosidic bonds which allowed the sequences to be determined. Several fragments resulting from cleavages across the sugar ring permitted the assignment, in some cases, of the linkage positions between the sugar residues. The natriated molecule yielded several fragments of this type which were not observed when the protonated molecule was selected as the precursor ion. Use of these techniques gave the complete sequence and linkage characterization of the disaccharide and complete sequence and partial linkage information for the two higher oligosaccharides. PMID- 1422132 TI - Fine sugar specificity of the Butea frondosa seed lectin. AB - Various monosaccharides and oligosaccharides were used to define the specificity of the Butea frondosa lectin using the hapten inhibition technique of human erythrocyte agglutination. Although B. frondosa lectin exhibited higher affinity for N-acetylgalactosamine, lactose and N-acetyllactosamine appeared to be relatively good inhibitors of haemagglutination. The behaviour of N acetyllactosamine-type oligosaccharides and glycopeptides on a column of B. frondosa lectin immobilized on Sepharose 4B showed that the sugar-binding specificity of the lectin is directed towards unmasked N-acetyllactosamine sequences. Substitution of these N-acetyllactosamine sequences by sialic acid residues completely abolished the affinity of the lectin for the saccharides. The presence of one or several alpha Fuc(1-3)GlcNAc groups completely inhibited the interaction between the glycopeptides and the lectin. Substitution of the core beta-mannose residue by an additional bisecting beta(1-4)GlcNAc residue decreases the affinity of the lectin for these structures as compared with the unsubstituted ones. PMID- 1422133 TI - Application of chemically desialylated and degalactosylated human glycophorin for induction and characterization of anti-Tn monoclonal antibodies. AB - Human erythrocyte glycophorin was desialylated by mild acid hydrolysis and degalactosylated by Smith degradation. Two monoclonal antibodies (Tn5 and Tn56) obtained by immunization of mice with this 'artificial' Tn antigen were characterized and compared in some experiments with two antibodies (BRIC111 and LM225) obtained in other laboratories by immunization with Tn erythrocytes. The specific binding of the antibodies to glycophorins desialylated and degalactosylated on the nitrocellulose blot and to asialo-agalactoglycophorin coated ELISA plates, and reactions with authentic Tn antigen served for identification of their anti-Tn specificity. The antibodies were further characterized in inhibition assay with various glycoproteins. The antibody Tn5 (similar to BRIC111) was shown to be specific for human erythrocyte Tn antigen, whereas Tn56 reacted strongly with different glycoproteins carrying O-linked GalNAc alpha- residues, and was strongly bound to the murine adenocarcinoma cell line Ta3-Ha. The antibodies Tn5, Tn56 and BRIC111 were similarly inhibited by ovine submaxillary mucin (OSM) and asialoOSM, but the antibody LM225 showed a distinct preference in reaction with OSM (sialosyl-Tn antigen). The results show that Tn antigen, obtained by chemical modifications of human glycophorin, enables the preparation and characterization of anti-Tn monoclonal antibodies, without using rare Tn erythrocytes. PMID- 1422134 TI - Inositol acylation of glycosylphosphatidylinositol membrane anchors: what it is, and why it may be important. PMID- 1422135 TI - Use of resorufin-labelled N-glycopeptide in a high-performance liquid chromatography assay to monitor endoglycosidase activities during cultivation of Flavobacterium meningosepticum. AB - Peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine amidase F (PNGase F) and endo beta-N-acetyl glucosaminidase F (Endo F) activities were monitored during cultivation of Flavobacterium meningosepticum using a new fluorescence-HPLC procedure based on a commercially available substrate. The PNGase F activity reached a maximum level at the end of the log phase and remained constant during the stationary phase, while Endo F continuously increased until late stationary phase. PNGase F obtained at the end of the log phase was less contaminated by other proteins compared with late stationary phase. PMID- 1422136 TI - Glycopeptidolipids--a new class of artificial antigens with carbohydrate determinants. Synthesis of artificial antigen with type-specific oligosaccharide hapten from Neisseria meningitidis group B. AB - Synthetic lipopeptide N-palmitoyltyrosyl-seryl-seryl-asparaginyl-alanine, an analogue of B-mitogenic tripalmitoyl-pentapeptide from Escherichia coli lipoprotein, was coupled with an oligosaccharide hapten from Neisseria meningitidis lipooligosaccharide to give a glycopeptidolipid conjugate--the artificial antigen of a new type processing the type-specific microbial determinant. PMID- 1422137 TI - Ion-spray mass spectrometric analysis of glycosaminoglycan oligosaccharides. AB - Oligosaccharides from hyaluronic acid and chondroitin 6-sulfate were prepared by digestion with testicular hyaluronidase and separated according to their degree of polymerization by gel-permeation chromatography. These materials were successively analyzed by negative-mode ion-spray mass spectrometry with an atmospheric-pressure ion source. An ion-spray interface was used to produce ions via the ion evaporation process, producing mass spectra containing a series of molecular species carrying multiple charges. Using two adjacent multiply charged molecular ions, the exact molecular weights up to the tetradecasaccharide were calculated with a precision of +/- 1 dalton. This type of mass spectrometry was also demonstrated to be feasible for the analysis of mixtures of oligosaccharides, including tetra-, hexa-, octa- and decasaccharides, from hyaluronic acid or chondroitin 6-sulfate without separation. Ion-spray mass spectrometry was thus shown to be applicable to the structural analysis of oligosaccharides from glycosaminoglycans. PMID- 1422138 TI - Control of glycoprotein synthesis: substrate specificity of rat liver UDP GlcNAc:Man alpha 3R beta 2-N-acetylglucosaminyltransferase I using synthetic substrate analogues. AB - UDP-GlcNAc: Man alpha 3R beta 2-N-acetylglucosaminyltransferase I (GlcNAc-T I; EC 2.4.1.101) is the key enzyme in the synthesis of complex and hybrid N-glycans. Rat liver GlcNAc-T I has been purified more than 25,000-fold (M(r) 42,000). The Vmax for the pure enzyme with [Man alpha 6(Man alpha 3)Man alpha 6](Man alpha 3)Man beta 4GlcNAc beta 4GlcNAc beta-Asn as substrate was 4.6 mumol min-1 mg-1. Structural analysis of the enzyme product by proton nuclear magnetic resonance spectroscopy proved that the enzyme adds an N-acetylglucosamine (GlcNAc) residue in beta 1-2 linkage to the Man alpha 3Man beta-terminus of the substrate. Several derivatives of Man alpha 6(Man alpha 3)Man beta-R, a substrate for the enzyme, were synthesized and tested as substrates and inhibitors. An unsubstituted equatorial 4-hydroxyl and an axial 2-hydroxyl on the beta-linked mannose of Man alpha 6(Man alpha 3)Man beta-R are essential for GlcNAc-T I activity. Elimination of the 4-hydroxyl of the alpha 3-linked mannose (Man) of the substrate increases the KM 20-fold. Modifications on the alpha 6-linked mannose or on the core structure affect mainly the KM and to a lesser degree the Vmax, e.g., substitutions of the Man alpha 6 residue at the 2-position by GlcNAc or at the 3- and 6-positions by mannose lower the KM, whereas various other substitutions at the 3-position increase the KM slightly. Man alpha 6(Man alpha 3)4-O-methyl-Man beta 4GlcNAc was found to be a weak inhibitor of GlcNAc-T I. PMID- 1422139 TI - Peptide-N4-(N-acetylglucosaminyl)asparagine amidase (PNGase) activity could explain the occurrence of extracellular xylomannosides in a plant cell suspension. AB - We have previously isolated mannoside and xylomannoside oligosaccharides with one or two terminal reducing N-acetylglucosamine residues from the extracellular medium of white campion (Silene alba) suspension culture. We have now demonstrated the presence of peptide-N4-(N-acetylglucosaminyl)asparagine amidase (PNGase) activity in cell extracts as well in the culture medium that could explain the production of those compounds. An additional xylomannoside, (GlcNAc)Man3(Xyl)GlcNAc(Fuc)GlcNAc, was characterized, and 1H- and 13C-NMR assignments for the oligosaccharide Man3(Xyl)GlcNAc(Fuc)GlcNAc were obtained using homonuclear and heteronuclear spectroscopy (COSY). PMID- 1422140 TI - Surface glycoprotein of human natural killer cells recognized by wheat germ agglutinin. AB - We analyzed surface glycoproteins of human natural killer (NK) cells by utilizing lectins. Among the lectins tested, wheat germ agglutinin (WGA) was found to bind preferentially to CD16(Leu11)-positive lymphocytes as determined by two-colour flow cytometry. Analysis of glycoproteins in the lysate prepared from NK cells with sodium dodecyl sulfate (SDS) gel electrophoresis followed by Western blotting and 125I labeled WGA staining revealed that a glycoprotein with an M(r) of 65 kDa was strongly bound to the lectin, but no corresponding glycoprotein was detected in the lysate of T lymphocytes. This glycoprotein (GP65) gave several spots in the pI range 4.1-4.6 on 2-dimensional gel electrophoresis. Sialidase treatment of GP65 resulted in a single spot on the 2-dimensional gel, suggesting that GP65 is heterogeneous in the degree of sialylation. GP65 was shown to be exposed on the cell surface, since it was radiolabeled with 125I by the lactoperoxidase-catalyzed method. We next isolated GP65 from human peripheral blood lymphocytes by a combination of chromatography on a cation-exchange column and a WGA-agarose column and preparative SDS gel electrophoresis. It is suggested that GP65 is a novel surface glycoprotein on human NK cells. PMID- 1422141 TI - Specificity of Amaranthus leucocarpus lectin. AB - We have demonstrated that Amaranthus leucocarpus lectin hemagglutinating activity was powerfully inhibited by the T-antigen, containing Gal(beta 1-3)GalNAc(alpha 1 3)Ser/Thr, and the Tn-antigen, which contains GalNAc(alpha 1-3)Ser/Thr. This suggests that the acetamido group at C-2 and the axial -OH at C-4 of the N-acetyl D-galactopyranosylamine ring are important for lectin binding. The hemagglutination assays also established that desialylated and Pronase-treated human type O erythrocytes with an M phenotype were better recognized than erythrocytes from all other blood groups. The recognition was dependent on pH and ionic strength. PMID- 1422142 TI - Comparison of the carbohydrate moieties of recombinant soluble Fc epsilon receptor (sFc epsilon RII/sCD23) expressed in Saccharomyces cerevisiae and Chinese hamster ovary cells. Different O-glycosylation sites are used by yeast and mammalian cells. AB - Recombinant human soluble low affinity receptor for the Fc portion of IgE (sFc epsilon RII/sCD23) was produced in Saccharomyces cerevisiae or Chinese hamster ovary cells and subjected to carbohydrate analysis. Applied methods included analytical SDS-PAGE, reversed phase HPLC, methylation analysis and sequential degradation with exoglycosidases. The results revealed that sFc epsilon RII derived from Chinese hamster ovary cells is glycosylated exclusively at Ser-147, containing mainly the trisaccharide Sia(alpha 2-3)Gal(beta 1-3)GalNAc, whereas the yeast derived glycoprotein was glycosylated at Ser-167 and contained only alpha-mannosyl residues. It is shown here for the first time that different amino acids of a given protein can be O-glycosylated when expressed in yeast or Chinese hamster ovary cells. PMID- 1422143 TI - Comparison of the NMR solution structure with the X-ray crystal structure of the activation domain from procarboxypeptidase B. AB - The NMR solution structure of the activation domain isolated from porcine procarboxypeptidase B is compared with the X-ray crystal structure of the corresponding segment in the intact proenzyme. For the region of the polypeptide chain that has a well-defined three-dimensional structure in solution, i.e., the backbone atoms of residues 11-76 and 25 amino acid side chains in this segment that form a hydrophobic core in the activation domain, the root-mean-square distance between the two structures is 1.1.A. There are no significant differences in average atom positions between the two structures, but only the NMR structure shows increased structural disorder in three outlying loops located along the same edge of the activation domain. These regions of increased structural disorder in the free domain coincide only partially with the interface to the enzyme domain in the proenzyme. PMID- 1422144 TI - Improved resolution in three-dimensional constant-time triple resonance NMR spectroscopy of proteins. AB - Two new protocols for the three-dimensional, triple resonance, constant-time HCA(CO)N NMR experiment are presented that significantly increase the experimental resolution attainable in the C alpha frequency dimension. Experimental verification of the new experiments is provided by spectra of the IIA domain of glucose permease from Bacillus subtilis. PMID- 1422145 TI - Sampling and efficiency of metric matrix distance geometry: a novel partial metrization algorithm. PMID- 1422146 TI - Toxin III of the scorpion Androctonus australis Hector: proton nuclear magnetic resonance assignments and secondary structure. AB - 1H NMR has been applied to a 3.5 mM, pH 5.4, solution of toxin III (64 amino acids) from venom of the scorpion Androctonus australis Hector. The resonance assignment strategy began by applying a generalized main-chain directed method for rapid identification and resonance assignments of secondary structures. The remaining resonances were assigned by the sequential method. Major structural features include a helix of 2 1/2 turns (residues 20-28) which is linked by two disulfide bridges to the central strand of a triple-stranded anti-parallel beta sheet. Turns were identified at residues 15-17, 47-49 and also at residues 51-53. Numerous NOEs have been observed between hydrophobic residues which suggest the presence of a hydrophobic core; these include Leu37, Leu23, Val47, Tyr14, Trp45 and Tyr5. The Trp45 and Tyr5 rings lie orthogonal to one another. No crystal structure has been solved for this AaH III toxin. Comparisons are made with other members of the scorpion toxin family. PMID- 1422147 TI - A 1H-15N NMR study of human c-Ha-ras protein: biosynthetic incorporation of 15N labeled amino acids. AB - A 1H-15N NMR study was performed on the GDP-bound form of a truncated human c-Ha ras oncogene product (171 amino acid residues). Resonance cross peaks of the backbone amide 1H-15N nuclei of a uniformly 15N-labeled protein were observed with heteronuclear single-quantum coherence spectroscopy (HSQC). In order to resolve overlapping cross peaks, selective 15N-labeling of one or two types of amino acid residues (Ala, Arg, Asx, Glx, Gly, His, Ile, Leu, Lys, Met, Phe, Ser, Thr, Tyr and/or Val) was carried out using appropriate E. coli mutant strains. By this procedure, all the backbone 1H-15N cross peaks were classified into amino acid types. PMID- 1422148 TI - The solution conformation of sialyl-alpha (2----6)-lactose studied by modern NMR techniques and Monte Carlo simulations. AB - We present a comprehensive strategy for detailed characterization of the solution conformations of oligosaccharides by NMR spectroscopy and force-field calculations. Our experimental strategy generates a number of interglycosidic spatial constraints that is sufficiently large to allow us to determine glycosidic linkage conformations with a precision heretofore unachievable. In addition to the commonly used [1H,1H] NOE contacts between aliphatic protons, our constraints are: (a) homonuclear NOEs of hydroxyl protons in H2O to other protons in the oligosaccharide, (b) heteronuclear [1H,13C] NOEs, (c) isotope effects of O1H/O2H hydroxyl groups on 13C chemical shifts, and (d) long-range heteronuclear scalar couplings across glycosidic bonds. We have used this approach to study the trisaccharide sialyl-alpha (2----6)-lactose in aqueous solution. The experimentally determined geometrical constraints were compared to results obtained from force-field calculations based on Metropolis Monte Carlo simulations. The molecule was found to exist in 2 families of conformers. The preferred conformations of the alpha (2----6)-linkage of the trisaccharide are best described by an equilibrium of 2 conformers with phi angles at -60 degrees or 180 degrees and of the 3 staggered rotamers of the omega angle with a predominant gt conformer. Three intramolecular hydrogen bonds, involving the hydroxyl protons on C8 and C7 of the sialic acid residue and on C3 of the reducing-end glucose residue, contribute significantly to the conformational stability of the trisaccharide in aqueous solution. PMID- 1422149 TI - Multidimensional 1H and 15N NMR investigation of glutamine-binding protein of Escherichia coli. AB - Specific and uniform 15N labelings along with site-directed mutagenesis of glutamine-binding protein have been utilized to obtain assignments of the His156, Trp32 and Trp220 residues. These assignments have been made not only to further study the importance of these 3 amino acid residues in protein-ligand and protein protein interactions associated with the active transport of L-glutamine across the cytoplasmic membrane of Escherichia coli, but also to serve as the starting points in the sequence-specific backbone assignment. The assignment of H epsilon 2 of His156 refines the earlier model where this particular proton forms an intermolecular hydrogen bond to the delta-carbonyl of L-glutamine, while assignments of both Trp32 and Trp220 show the variation in local structures which ensure the specificity in ligand binding and protein-protein interaction. Using 3D NOESY-HMQC NMR, amide connectivities can be traced along 8-9 amino acid residues at a time. This paper illustrates the usefulness of combining 15N isotopic labeling and multinuclear, multidimensional NMR techniques for a structural investigation of a protein with a molecular weight of 25,000. PMID- 1422150 TI - Sequence-specific resonance assignment and secondary structure of (1-71) bacterioopsin. AB - The conformation of chymotryptic fragment C2 of bacteriohodopsin (residues 1-71) was studied by 2D 1H NMR. The fragment was solubilized in a mixture of chloroform/methanol (1:1), 0.1 M LiClO4. Most of the resonances in 1H NMR spectra of fragment C2 were assigned using phase-sensitive DQF-COSY, TOCSY, and NOESY techniques. To simplify the assignment procedure for overlapping regions of NMR spectra, an analog of fragment C2 with leucines deuterated in beta-positions was used. Deuterium exchange rates for amide protons were measured in a series of TOCSY spectra. Two right-handed alpha-helical regions Pro8-Lys30 and Lys41-Leu62 were identified on the basis of NOE connectivities and deuterium exchange rates. The N-terminal part of the fragment (Ala2-Gly6) adopts the helical conformation stabilized by 3 hydrogen bonds. PMID- 1422151 TI - The effect of selective deuteration on magnetization transfer in larger proteins. AB - The effects of selective deuteration on calculated NOESY intensities have been analyzed for the structure of the E. coli trp aporepressor, a 25 kDa protein. It is shown that selectively deuterated trp aporepressor proteins display larger calculated NOESY intensities than those for the same interproton distances in the natural abundance protein. The relatively larger magnetization transfer is demonstrated by a comparison of the NOE build-up curves for specific proton pairs, and for the calculated NOE intensities of short-range NOEs to backbone amide protons. This increase in intensity is especially pronounced for the NHi NHi+1 cross peaks in the alpha-helical regions, and particularly for amide protons of two sequential deuterated residues. The effect is shown to be further intensified for longer mixing times. It is also shown that in all cases, each amide proton exhibits stronger NOEs to its own side chain, with an enhanced effect for deuterated derivatives. This theoretical analysis demonstrates that an evaluation of the relative NOE intensities for different selectively deuterated analogs may be an important tool in assigning NMR spectra of large proteins. These results also serve as a guide for the interpretation of NOEs in terms of distances for structure calculations based on data using selectively deuterated proteins. PMID- 1422152 TI - A refocused and optimized HNCA: increased sensitivity and resolution in large macromolecules. AB - A 3D optimized, refocused HNCA experiment is described. It is demonstrated to yield a dramatic increase in sensitivity when applied to [13C, 15N]-labeled human carbonic anhydrase II, a 29-kDa protein. The reasons for the gain in sensitivity are discussed, and 3 distinct areas for further development are indicated. PMID- 1422153 TI - A new 3D HN(CA)HA experiment for obtaining fingerprint HN-Halpha peaks in 15N- and 13C-labeled proteins. AB - A new 3D 1H-15N-13C triple resonance experiment is presented that provides in phase absorptive cross peaks between amide protons and alpha-protons of the same and the sequentially preceding residue. The experiment yields similar connectivities as those described previously by Montelione and Wagner (1990a) (J. Magn. Reson., 87, 183-188) and Kay et al. (1991) (J. Magn. Reson., 91, 84-92). However, the pulse sequence was designed to minimize the time that transverse coherence of the 13Calpha nucleus is present, since this nucleus has the shortest transverse relaxation time of all the nuclei involved in these experiments. This is achieved by using a coherence transfer pathway from 1HN to 15N, 13Calpha, 1Halpha and back to the 1HN. In the sequence described, transverse 13Calpha coherence is present only for a length of ca. 1/1J(Calpha-Halpha). This reduces loss of signal due to transverse relaxation. We tested the technique on uniformly 15N- and 13C-enriched T4 lysozyme. PMID- 1422154 TI - Solution conformation of human big endothelin-1. AB - The solution conformation of human big endothelin-1, a 38-residue peptide which serves as the putative precursor to the potent vasoconstrictor endothelin-1 has been examined by 1H NMR. NOEs were utilized as distance restraints in the distance geometry program DSPACE to generate initial structures. Further refinement of these structures was accomplished through molecular mechanics/molecular dynamics in an iterative process involving the incorporation of stereospecific assignments of prochiral centers and the use of back calculation of NOESY spectra. A family of structures consisting of a type II beta turn for residues 5-8 and an alpha-helix extending from residues 9-16 constitute a well-defined region, as reflected by the atomic root-mean-square (RMS) difference of 1.56 A about the mean coordinate positions of the backbone atoms (N, C, C alpha and O). This core region (residues 1-15) is very similar to the core residues of endothelin-1 (Donlan, M. et al. (1991) J. Cell. Biochemistry, S15G, 85). While the evidence from NOESY and coupling constant data suggests that the C-terminal region, residues 17-34, is not a mixture of randomly distributed chain conformations, it is also not consistent with a single chain conformation. Under the conditions studied, residues 17-38 in human big endothelin-1 in water at pH 3.0 between 20-30 degrees C appear to be represented by a series of conformers in dynamic equilibrium. PMID- 1422155 TI - 1H and 15N resonance assignments and secondary structure of the human thioredoxin C62A, C69A, C73A mutant. AB - The complete assignment of 1H and 15N backbone resonances and near-complete 1H side-chain resonance assignments have been obtained for the reduced form of a mutant of human thioredoxin (105 residues) in which the three non-active site cysteines have been substituted by alanines: C62A, C69A, C73A. The assignments were made primarily on the basis of three-dimensional 15N-separated nuclear Overhauser and Hartmann-Hahn spectroscopy, in conjunction with two-dimensional homonuclear and heteronuclear correlation experiments. Based on comparisons of short-range and interstrand nuclear Overhauser effects, patterns of amide exchange, and chemical-shift differences, the structure appears essentially unchanged from that of the previously determined solution structure of the native protein [Forman-Kay, J.D. et al. (1991) Biochemistry, 30, 2685-2698]. An assay for thioredoxin shows that the C62A, C69A, C73A mutant retains activity. The assignment of the spectrum for this mutant of human thioredoxin constitutes the basis for future studies aimed at comparing the details of the active-site conformation in the reduced and oxidized forms of the protein. PMID- 1422156 TI - Simulation of NOESY spectra of DNA segments: a new scaling procedure for iterative comparison of calculated and experimental NOE intensities. AB - A new algorithm for simulation of two-dimensional NOESY spectra of DNA segments has been developed. For any given structure, NOE intensities are calculated using the relaxation matrix approach and a new realistic procedure is suggested for 1:1 comparison of calculated and experimental intensities. The procedure involves a novel method for scaling of calculated NOE intensities to represent volumes of digitised cross peaks in NOESY spectra. A data base of fine structures of all the relevant cross peaks with Lorentzian line shapes and in-phase components, is generated in a digitised manner by two-dimensional Fourier transformation of simulated time domain data, assuming a total intensity of 1.0 for each of the cross peaks. With this procedure, it is shown that the integrated volumes of these digitised cross peaks above any given threshold scale exactly as the total intensity of the respective peaks. This procedure eliminates the repetitive generation of digitised cross peaks by two-dimensional Fourier transformation during the iterative process of structure alteration and NOE intensity calculation and thus enhances the speed of DNA structure optimization. Illustrative fits of experimental and calculated spectra obtained using the new procedure are shown. PMID- 1422157 TI - Quantitative comparison of experimental and simulated NOE intensities: correlation with accuracy of oligonucleotide structure determination. AB - The relation between the match of experimental and simulated NOE intensities with the accuracy of structure determination of oligonucleotides has been investigated. A hypothetical experimental spectrum of the oligonucleotide d(CCAACGTTGG) from its known X-ray crystallographic structure (Prive, G.G. et al. (1991) J. Mol. Biol., 217, 177-199) has been generated with simplifying assumptions of single correlation time, leakage rate etc., and this spectrum has been simulated imposing various constraints in a manner as one would do in a real case. The hypothetical spectrum represents the case of an infinitely good experimental spectrum and therefore the study of quality of fit against quality of structure represents the limiting case of real situations. It has been shown that even with a limited number of NOEs, it is possible to approach the correct structure of the molecule by demanding a highly accurate fit between experimental and simulated NOE intensities. Distance geometry calculations have been used to probe the extent of structural degeneracies in the NOE intensity matching exercise. PMID- 1422158 TI - Quantitative measurement of small through-hydrogen-bond and 'through-space' 1H 113Cd and 1H-199Hg J couplings in metal-substituted rubredoxin from Pyrococcus furiosus. AB - A method is described for measurement of small unresolvable heteronuclear J couplings. The method is based on quantitative analysis of a phase-purged heteronuclear spin-echo difference spectrum, and is demonstrated for measuring 1H 113Cd and 1H-199Hg J couplings in metal-substituted rubredoxin (M(r) approximately 5.4 kDa) from Pyrococcus furiosus. Couplings from cadmium to backbone amide protons that are hydrogen bonded to the Cys-S atoms directly bonded to Cd vary from smaller than 0.3 to 1.8 Hz; a 'through-space' coupling between Cd and the protons of an alanine methyl group was measured to be 0.3 Hz. Couplings to 199Hg are significantly larger and fall in the 0.4-4 Hz range. PMID- 1422159 TI - Activity patterns in elementary and high school students exposed to oxidant pollution. AB - We investigated activity patterns of 17 elementary school students aged 10-12, and 19 high school students aged 13-17, in suburban Los Angeles during the oxidant pollution season. Individuals' relationships between ventilation rate (VR) and heart rate (HR) were "calibrated" in supervised outdoor walking/jogging. Log VR was consistently proportional to HR; although "calibrations" were limited by a restricted range of exercise, and possibly by artifact due to mouthpiece breathing, which may cause overestimation of VR at rest. Each subject then recorded activities in diaries, and recorded HR once per minute by wearing Heart Watches, over 3 days (Saturday-Monday). For each activity the subject estimated a breathing rate--slow (like slow walking), medium (like fast walking), or fast (like running). VR ranges for each breathing rate and activity type were estimated from HR recordings. High-school students' diaries showed their aggregate distribution of waking hours as 68% slow inside, 8% slow outside, 10% medium inside, 9% medium outside, 1.5% fast inside, 1.5% fast outside. Elementary students' distribution was 47% slow inside, 15% slow outside, 20% medium inside, 12% medium outside, 2.5% fast inside, 3.5% fast outside. Sleep occupied 38% of high-school students' and 40% of elementary students' time; HR were generally lower in sleep than in slow waking activity. High school students' mean VR estimates were 13 L/min for slow breathing, 18 for medium, and 23 for fast; elementary students' were 14 slow, 18 medium, and 19 fast. VR distributions were approximately lognormal. Maximum estimated VR were approximately 70 L/min in elementary and approximately 100 L/min in high school students. Compared to adults studied similarly, students reported more medium or fast breathing, and had equal or higher VR estimates during slow and medium breathing despite their smaller size. These results suggest that, relative to body size, young people inhale larger doses of outdoor air pollutants than adults. PMID- 1422160 TI - Measurement of personal exposure to NO2 in Sweden--evaluation of a passive sampler. AB - A passive (filter badge) sampler for personal NO2 exposure measurements was tested in a laboratory setting (exposure chamber), and in the field--outdoors, during periods of high relative humidity (mean 85%) and low temperature (-5 to +10 degrees C), and indoors, in an ice-hockey arena--using chemiluminescence as a reference method. Parallel measurements of NO2 in the exposure chamber (concentration range 100-825 micrograms NO2/m3) for 15, 30, and 60 min sampling periods, showed good agreement between methods. The concentrations obtained with passive samplers were 78 to 122% (mean 94%, SD +/- 11, N = 39) of those obtained with chemiluminescence, using a sampling rate (K'OG) of 0.14 cm/sec. The detection limits were 320, 160, and 80 micrograms NO2/m3 for 15, 30, and 60 minutes of sampling, respectively. Outdoors (concentration range 15-102 micrograms NO2/m3, concentrations obtained with passive samplers were consistently lower than concentrations obtained with chemiluminescence (mean 79%, SD +/- 9.3%, range 61-95%, N = 25), using the K'OG of 0.14 of cm/sec (Passive samplerNO2 = 0.67ChemilumNO2 + 4.5). A better agreement between concentrations obtained with passive samplers and chemiluminescence was achieved with a K'OG of 0.11 cm/sec (mean 100%, SD +/- 12%, range 78-121%, Passive samplerNO2 = 0.84 ChemilumNO2 + 6.4). Indoors (concentration range 210-3895 micrograms NO2/m3), concentrations obtained with passive samplers were 70 to 113% (mean 90%, SD +/- 16%) of the concentrations obtained with chemiluminescence (Passive samplerNO2 = 1.00ChemilumNO2 - 93) using a K'OG of 0.10 cm/sec. Duplicate samples collected indoors N = 18) and outdoors (N = 31) showed a variability (coefficient of variation, or CV) of less than 6%. It was concluded that the passive sampler is useful for measuring personal daily exposure as well as peak exposure. It is necessary to determine sampling rates for various environmental conditions. PMID- 1422161 TI - Assessment of exposure to radon decay products in realistic living conditions. AB - The development of an automated system for activity-weighted size distribution measurements now permits more complete exposure and dose assessment for indoor radon decay products. Exposures characterized by the semi-continuous measurement of activity-weighted size distributions of radon decay products were obtained over four test periods in three normally occupied houses, two of which were occupied by cigarette smokers. These measured activity size distributions were used to calculate exposure-dose conversion coefficients and the annual effective doses. These doses were found to be approximately two-fold higher than the values derived conventionally from the measured radon concentration, on the assumption that indoor exposure to 20 Bq m-3 radon gas concentration corresponds to an annual effective dose 1 mSv y-1. The degree to which aerosol-measurement-based dose estimates were higher than radon-gas-based estimates was found to be influenced if the study house occupant was a cigarette smoker. Reassessment of the measured PAEC-weighted radon progeny particle size distribution in terms of the classical "unattached" and "attached" modes yielded lower estimates of the exposure-effective dose conversion coefficient that were similar to the reference values derived from a recent study by the National Research Council. Thus, by not resolving the measured radon progeny PAEC that is associated with particles intermediate in size between the two classical radon progeny modes, the estimated annual effective doses were also found to be similar to the values derived conventionally from the measured radon gas concentration. It is concluded that the observed presence of 4 to 13% of the radon progeny PAEC in the size-range 1.5 to 15 nm diameter is a dosimetrically significant factor that appears to be commonplace in various home environments. PMID- 1422162 TI - Human exposure to pollutants in Poland. AB - Serious environmental problems caused by decades of mismanagement of Poland's natural resources have been brought to light in recent years. All environmental media--air, water, food, and soil--have been burdened with toxic chemicals. Some environmental problems are so severe that the sources of pollution and the mitigation techniques needed are obvious, requiring no further research, but rather common sense, monies, and determination to implement the necessary controls and mitigation procedures. This paper will not address these obvious cases. Rather it will address that spectrum of environmental problems which requires a better understanding of public health risk in order to develop effective risk management strategies. Because these problems are numerous and monies limited, policy makers will need to set priorities both for research projects and control options. Using environmental concentration data presently available from Poland (especially for air), the paper will estimate human exposures, will point out research and monitoring needs, and hopefully, will lend credence to the concept that environmental policies and risk reduction strategies will be most effective if the Total Human Exposure Concept is used as the guiding scientific principle in risk assessment and management programs. PMID- 1422163 TI - Elimination kinetics of volatile organics in humans using breath measurements. AB - During the past decade significant strides have been made toward understanding the sources and factors which lead to volatile organic chemical (VOC) exposure in the general population. Less is known, however, about the impact of low-level environmental exposure on human health. Investigations are underway in a number of laboratories in an effort to determine the uptake, distribution, metabolism, and elimination kinetics for VOCs in humans. We examined the elimination kinetics for the third phase for ten VOCs--1,1,-trichloroethane, trichloroethylene, tetrachloroethylene, benzene, toluene, m,p-xylenes, o-xylene, ethylbenzene, p dichlorobenzene, and limonene--in human subjects. Subjects were exposed to a variety of common consumer products and breath samples were collected post exposure while the subjects spent up to 10 hr in a clean air environment. VOCs from breath samples were collected into canisters or onto Tenax GC cartridges and analyzed by gas chromatography-mass spectrometry. Exponential modeling of the decay data was performed to obtain kinetic parameters. The half-lives for trichloroethylene and 1,1,1-trichloroethane were approximately 5 to 8 hr for the four subjects. In general, the magnitude and range of variability was larger for toluene, limonene, and p-dichlorobenzene than for the other VOCs; the elimination rate spanning a few hours to a day or two. Thus, VOCs exhibit relatively short residence times in the body relative to other halo-carbons, such as polychlorinated biphenyls and dioxins. PMID- 1422164 TI - Airborne asbestos levels in buildings: maintenance worker and occupant exposures. AB - A substantial number of air samples have been collected during the past few years to measure airborne asbestos levels in buildings with asbestos-containing materials (ACM). These samples fall into two categories: (i) samples collected to measure the exposure of workers while they were engaged in routine maintenance and repair activities; and (ii) samples collected during normal building activity to measure prevalent levels in buildings. The measurements derived from these samples have been compiled and summarized to provide estimates of the airborne asbestos exposure of workers engaged in routine maintenance and repair work and by other building occupants. These data indicate that maintenance and repair workers in buildings with ACM, after accounting for the frequency and duration of these types of activities, have annual exposure levels ranging from a median value of 0.002 fibers per cubic centimeter (f/cc) per year to 0.02 f/cc per year at the 90th percentile. Building occupants not involved in maintenance and repair work experience average exposure levels ranging from 0.00003 f/cc to 0.0005 f/cc. PMID- 1422165 TI - "Secondary" and drug-induced mood, anxiety, psychotic, catatonic, and personality disorders: a review of the literature. PMID- 1422166 TI - Anticonvulsants in the treatment of bipolar disorder. AB - In the last decade, a proliferation of research has emerged concerning the use of somatic treatments with anticonvulsant properties, e.g., carbamazepine, valproate, clonazepam, oxcarbazepine, and electroconvulsive therapy (ECT), for patients with bipolar disorder. A sufficient number of controlled studies have been conducted to allow critical review of the evidence supporting the efficacy of these treatments for acute bipolar manic and depressive episodes, as well as for the prevention of subsequent episodes. Further research is needed to establish the prophylactic efficacy of anticonvulsants as maintenance therapies and, perhaps most importantly, to provide clinical and biological predictors of response. PMID- 1422167 TI - Regional cerebral glucose metabolism and attention in adults with a history of childhood autism. AB - Sixteen high-functioning adults with a history of childhood autism and 26 normal control subjects underwent [18F]fluoro-2-deoxyglucose positron-emission tomography to assess regional cerebral glucose metabolic rate (GMR). Autistic patients had a left > right anterior rectal gyrus asymmetry, as opposed to the normal right > left asymmetry in that region. Patients also showed low GMR in the left posterior putamen and high GMR in the right posterior calcarine cortex. Brain regions with GMR > 3 SD from the normal mean were more prevalent in patients than in control subjects. This variable pattern of abnormal activity is consistent with heterogeneous neurophysiological etiology; group differences in striatum and cortex may represent a final common pathway. PMID- 1422168 TI - Neurologic outcome of patients with dorsolateral prefrontal leukotomy. AB - Few controlled studies of neurologic function in frontal leukotomy patients have been done. The authors compared neurologic examinations of patients who had bilateral leukotomies with those of psychiatric control subjects matched for age, diagnosis, and duration of illness. Cranial nerve dysfunction, abnormal involuntary movements, and primitive reflexes were common. No significant differences between the two patient groups were found. The leukotomized patients were less irritable than control subjects and had statistically higher seizure and death rates. Neurologic abnormalities are, thus, common in elderly chronic psychiatric patients. Surprisingly, patients with bilateral prefrontal leukotomy do not differ from well-matched psychiatric controls on most clinical tests of neurologic function. PMID- 1422169 TI - Visual perceptual dysfunction in patients with schizophrenic and affective disorders versus control subjects. AB - Visual perception was evaluated with standard tests for 26 hospitalized patients with schizophrenia, 23 hospitalized patients with affective disorders, and 60 control subjects. Both patient groups differed significantly from the control group on low amplitude of accommodation, esophoria or exophoria, vergence duction suppression, and convergence and divergence recovery ductions. Only the affective group showed significantly reduced fusion at near distance, and only the schizophrenic group differed significantly from control subjects on disorganized left apex formation. These findings appear to confirm the presence of visual perceptual disorders that can cause disability in psychiatric patients, with important research and rehabilitation implications. PMID- 1422170 TI - Neuropsychological discriminators of long-term inpatient or outpatient status in chronic schizophrenia. AB - This study investigates specific neuropsychological functions discriminating schizophrenic patients with hospitalization beyond 18 months from patients residing in the community without rehospitalization beyond 3 years. Twenty-six Research Diagnostic Criteria-diagnosed chronic schizophrenic outpatients and 26 inpatients matched for sex, ethnicity, socioeconomic status, and chronicity completed a comprehensive neuropsychological battery and responded to an inventory of psychopathology. Discriminant function analyses showed that measures of motor coordination, preservation, memory, and attention discriminated between patient groups. Bilateral simultaneous fine motor coordination was the most potent discriminator between patient groups, independent of psychopathology. Implications for treatment and research on course and outcome in schizophrenia are discussed. PMID- 1422172 TI - Pathological lying associated with thalamic dysfunction demonstrated by [99mTc]HMPAO SPECT. AB - The authors report a case in which pathological lying is associated with right hemithalamic dysfunction as shown by [99mTc]HMPAO SPECT brain scanning. This association has not been demonstrated previously and is noteworthy because it supports the hypothesized roles of the thalamus and associated brain regions in the modulation of behavior and cognition. PMID- 1422171 TI - Bipolar disorder in idiopathic dystonia: clinical features and possible neurobiology. AB - The authors report 5 patients with bipolar disorders in the context of primary idiopathic dystonia. Four patients had DSM-III-R bipolar disorder, mixed, and one had cyclothymic disorder as diagnosed using the Structured Clinical Interview for DSM-III-R (SCID). All cases of bipolar disorder manifested rapid cycling. Three patients with bipolar disorder experienced onset of this illness soon after the onset of cervicocranial dystonia (5 neck dystonia, 4 craniofacial, 2 brachial, 1 vocal cord, 1 thoracic). These cases apparently represent a first report of bipolar disorders in dystonia. Clinical management, relevant literature, and putative neurobiology are reviewed. PMID- 1422173 TI - Neurologic signs in patients with paranoid and nonparanoid schizophrenia. AB - Previous research found that both persons with schizophrenia and their unaffected relatives had significantly more neurologic signs than normal controls. As hypothesized, in this study neurologic signs were significantly greater in patients with nonparanoid than paranoid schizophrenia; the difference was greatest for "hard" signs. PMID- 1422174 TI - Dissociation of neurocognitive deficits in a monozygotic twin pair concordant for schizophrenia. AB - Cognitive impairment varies markedly among schizophrenic individuals, although the reason for this is unknown. A monozygotic twin pair concordant for schizophrenia was evaluated using electrophysiological and neurobehavioral measures. Each twin showed a distinctive pattern of deficits; furthermore, clinical course and electrophysiological activity were not consonant with social and neurobehavioral functioning. Results suggest complex interrelationships between neurocognitive functioning and clinical presentation in schizophrenia. PMID- 1422175 TI - Prolonged postictal encephalopathy in two patients with clozapine-induced seizures. AB - Two patients with prolonged postictal encephalopathy lasting 63 and 72 hours, respectively, following seizures with clozapine are reported. Clozapine alters the EEG in a majority of patients treated, with seizure frequency as high as 5 10% in doses above 600 mg/d. Prolonged postictal encephalopathy following a clozapine-induced seizure has not been previously reported but may be an important side effect of this medication. Pharmacologic and clinical issues are discussed. PMID- 1422177 TI - Anticoagulant therapy for dementia: informed consent. PMID- 1422176 TI - Skeptics and enthusiasts in neuropsychiatry. PMID- 1422178 TI - The effect of adding Br or Zn supplements to the dialysate on the concentrations of Br and Zn in the blood of hemodialysed patients. AB - The effect of adding Br or Zn supplementation to the dialysate on the concentrations of Br and Zn in the blood of hemodialysed patients, is investigated. Patients with end-stage renal failure on hemodialysis show an abnormal trace element pattern. Our patients showed lowered serum Br and Zn concentrations. Four patients were subjected to dialysates with varying Br content. The impact on their serum and packed cells concentrations was evaluated. The supplementation resulted in an increase in the concentrations in serum and in packed cells. The Br concentration in serum and packed cells closely followed the dialysate content. In order to restore the Zn concentration to the normal level a ZnCl2 solution was added to the dialysate of 4 other patients. Zn accumulated in the patient as a consequence of its diffusion against the concentration gradient. PMID- 1422179 TI - Cadmium uptake by brush border membrane vesicles from the rabbit renal external cortex. AB - Brush border membrane vesicles (BBMV) isolated from the rabbit renal external cortex were used to investigate inorganic cadmium (Cd) uptake. BBMV were incubated during 1 to 60 min in a buffered solution containing 10 to 200 mumol/L Cd (CdCl2), and uptake was determined using a rapid filtration technique. Cd uptake by BBMV was time-and concentration-dependent. At the lowest concentration (10 mumol/L), Cd uptake was nearly complete (70% of the plateau value, which was obtained after 10 min) within 1 min. At the highest concentration (200 mumol/L), the percentage of Cd uptake during the first minute was smaller (50%) and a slower component of uptake appeared. From additional experiments where Cd-loaded BBMV were submitted to an osmotic shock or to variations of extravesicular osmolality, it was concluded that the uptake of Cd by BBMV resulted essentially from membrane binding and not from intravesicular accumulation. The change in pH from 7.4 to 5.8 under iso- or hypotonic conditions removed about 40% of Cd bound to the BBMV, indicating that Cd binding to the membrane is pH sensitive. Thus, binding to the brush border membrane constitutes an initial step for inorganic Cd entry into renal epithelial cells. PMID- 1422180 TI - Zinc in lymphocytes--the assessment of zinc status in patients with Crohn's disease. AB - A group of 26 Crohn's disease patients was compared to a healthy control group with regard to their zinc status in plasma, urine, hair, and lymphocytes. A method for lymphocyte preparation, which was in part newly designed, was used; it proved to be very effective as to recovery and purity of the harvested cell fraction. Results of the study suggest that an accurate estimation of zinc status can be more reliably obtained by determination of lymphocyte zinc--provided the cell preparation described is used--than by using any other of the examined body compartments. PMID- 1422181 TI - Historical perspective on the identification of type I iodothyronine deiodinase as the second mammalian selenoenzyme. PMID- 1422182 TI - Health evaluation of an aerosol formed in the fumes from mild steel welding electrodes. AB - Welding is one of the processes which cause multivarious problems to health. It requires considerable attention because of its severe hazards. During welding very harmful fumes and heat are emitted which have adverse effects on the health of the welder and people working in his vicinity. In the present work microfibre glass filter paper (GF/A) was found to be the preferable media for sampling of the fumes from mild steel electric welding electrodes for the evaluation of the trace elemental composition of the fumes. Using neutron activation analysis considerable amounts of the most harmful elements such as Ba, Co, Cr, Sb, Rb, Sc, As and Fe were observed. PMID- 1422183 TI - Trace elements in hydatid disease. AB - The serum and cyst fluid levels of selenium, zinc and copper were investigated both in patients and sheep with hydatid cysts. Results were compared with those of healthy subjects in both species. The serum values of Se, Zn and Cu in healthy subjects were 60.24 +/- 1.96 micrograms/L, 0.59 +/- 0.07 mg/L, and 1.01 +/- 0.08 mg/L, respectively. The corresponding serum values of the three trace elements in patients with hydatidosis were 41.30 +/- 1.94 micrograms/L, 1.27 +/- 0.08 mg/L, and 0.89 +/- 0.09 mg/L. These results show a decrease in Se and Zn, and a rise in Cu in sera of patients with hydatid disease. Similar results were obtained in infested sheep as related to the healthy control animals. Our results on the three trace elements were found to correlate well with the incidence of cirrhosis, malignant and infectious diseases and arthritis. Se was not detectable in cyst fluid, while Cu and Zn levels were found significantly lower than serum levels. Cu and Zn levels in cyst fluid showed no difference in both species. Variations in serum Cu, Zn and Se levels were insignificant with regard to the genus of the host and the fertile capacity of the hydatid cyst. PMID- 1422184 TI - Problems associated with the use of exclusion-diffusion chromatography for identification of zinc ligands in human milk. AB - The effect of operating conditions used in gel filtration, i.e. the type of gel and elution buffer, on the qualitative and quantitative distribution of zinc in human milk was studied. The gels used were Sephadex G10 and G15, Biogel P2 and Trisacryl GF05. The three elution buffers used were 0.05 M Tris-HCl, pH = 7.4, 0.05 M Tris-acetate, pH = 7.4 and 0.1 M ammonium acetate, pH = 6.5. Ultrafiltration was used as an additional technique for the verification of a number of the results obtained. Zinc ligands in human milk are, possibly, serum albumin and citric acid. The results showed a gel effect, which was greater on the identification and quantitation of the low molecular-weight ligand (the percentage of zinc associated with citric acid was lower with Biogel P2). The elution buffer had a considerable effect, particularly when quantifying the protein-bound fraction. The percentage of zinc coeluted with proteins decreased when the elution buffer contained acetate ions. The combination of Sephadex G15 and 0.05 M Tris-HCl, pH = 7.4 was found to be the best compromise. Zinc distribution with this system was 35-44% of zinc coeluted with proteins and 18 22% with citric acid. PMID- 1422186 TI - Inhibitory effects of isolated inositol phosphates on zinc absorption in humans. AB - Inositol hexa phosphate (phytic acid) forms poorly soluble complexes with zinc, resulting in reduced absorption. During food preparation and processing phytate is partly hydrolyzed to lower inositol phosphates which have other binding properties. Zinc absorption in humans was measured in 18 women (22-37 a) by use of extrinsic labelling of meals with 65Zn and measurement of whole body retention. Inositol phosphates--400 mumol of the hexa phosphate form (IP-6), 200 and 400 mumol of the penta phosphate form (IP-5) and 400 mumol of the tetra phosphate form (IP-4)--were added to white bread and served with 200 mL of milk. The zinc content of the meal was 22 mumol. The absorption of zinc (65Zn) from white bread with no detectable phytate content was 43.3 +/- 17.9% (mean +/- SD) and from the breads with added 400 mumol of IP-6: 14.3 +/- 3.2%; 200 mumol of IP 5: 27.1 +/- 5.3%; 400 mumol of IP-5: 18.1 +/- 4.2%; and 400 mumol of IP-4: 41.5 +/- 11.3%. The results indicate that IP-6 and IP-5 have zinc-absorption depressing properties, while IP-4 added in isolated form is relatively inert as regards zinc absorption. However, a comparison with earlier obtained results from zinc absorption studies indicate that results obtained with isolated inositol phosphates can not directly be extrapolated to the phytate contents of foods. PMID- 1422185 TI - Concentration changes of electrolytes in serum of chronic chagasic myocardiopathic patients. Sodium, potassium, chloride, calcium, inorganic phosphorus and magnesium. AB - Sodium, potassium, chloride, calcium, inorganic phosphorus (Pi) and magnesium contents in the serum of 75 myocardiopathic chagasic patients together with that in 29 healthy controls were determined. Blood samples were taken by catheterization from the superior cava vein (SCV), coronary sinus (CS), pulmonary artery (PA) and a peripheral artery, usually the femoral (FA). The results show that the average serum sodium, potassium, chloride, calcium and PI were invariably different in most samples, except the levels of potassium in SCV and Pi levels in FA. The serum concentration of magnesium was significantly different only in the blood of CS. In general one can observe that in the chagasic patients the serum sodium, chloride and calcium tend to diminish while serum potassium, Pi and magnesium tend to increase, especially in CS blood. The coronary gradient indicates that sodium, chloride and calcium tend to deposit in heart tissues, whereas the other elements (potassium, magnesium and Pi) tend to be released from this tissue. The systemic and peripheric gradients suggest that the chemical elements under study tend either to deposit in/or be released from different tissues depending on the course of development of the chagasic myocardiopathy. PMID- 1422187 TI - Monocyte mediated cytotoxic activity against melanoma. AB - The appearance of macrophages in human tumours, the so called tumour-infiltrating or tumour-associated macrophages (TIM or TAM) has suggested a role for these cells in host defence mechanisms against cancer. In this review we discuss monocyte-mediated cytotoxic activity against melanoma, as reported by a number of different authors. Although most studies described in this review have used melanoma cell lines as targets for monocyte/macrophage cytotoxicity, it would be incomplete if cytotoxicity against other target cells such as K562 or WEHI-164 is not discussed. At least two distinct mechanisms of killing by monocytes/macrophages can be distinguished; direct recognition and cytotoxicity by the effector cells and antibody-mediated lysis of the tumour cells (antibody dependent cellular cytotoxicity, ADCC). Both types of cytotoxicity will be discussed. PMID- 1422188 TI - Glutathione content of human malignant melanoma cell lines: correlation of flow cytometric and biochemical assays, and application to human tumour aspirates. AB - We measured the glutathione content of a panel of human malignant melanoma cell lines by flow cytometry after staining with mercury orange, using visible light (488 nm) excitation, and compared the values obtained with those measured biochemically using a modified Tietze assay. Glutathione levels were depleted by culturing cells with various concentrations of buthionine sulphoximine to provide a suitable spread of glutathione concentrations. The two assays showed good correlation (r = 0.93). We found a number of technical factors to be critically important. In particular, the conditions of staining, cell number, and method of mixing media, cells and stain were responsible for wide variations in fluorescence intensity. We applied the flow cytometric technique to cell suspensions obtained by fine needle aspiration biopsy of human malignant melanoma deposits, and observed a proportion of cells with high glutathione levels in many samples. The results confirm the feasibility of measuring glutathione content by visible light flow cytometry, and raise the possibility of monitoring glutathione content as an indicator of drug resistance in clinical therapy of human malignant melanoma. PMID- 1422189 TI - A possible role for cysteine proteinase and its inhibitors in motility of malignant melanoma and other tumour cells. AB - The metastasis of malignant tumour cells depends on their rapid replication, and their ability to adhere to the matrix of a biological barrier such as basement membrane, to degrade the matrix, and to migrate through this more permeable barrier. Secreted enzymes, including the cysteine proteinases cathepsins B and L, are known to degrade basement membrane components. Using a barrier-free substratum we studied the possible role of cysteine proteinases in influencing the motility per se of metastatic cells. We found that stefins, the natural inhibitors of cysteine proteinases, markedly decreased the stimulated motility of both human melanoma cells and W256 carcinosarcoma cells at low concentrations (0.5 microM). A stefin also inhibited melanoma cell adherence, but to a lesser extent than motility. Additionally, synthetic inhibitors (E-64, diazomethyl ketones) of cysteine proteinases were found to depress stimulated motility of W256 cells. These results suggest that cysteine proteinases and their inhibitors may have a direct role in the development of a migratory response per se in tumour cells. PMID- 1422190 TI - Inactive cathepsin B-like enzyme in human melanoma culture medium. AB - An inactive cathepsin B-like enzyme with a molecular mass of 40 kD was found in a human melanoma culture medium. The inactive form of this enzyme was converted into an active form with a molecular mass of 28 kD by pepsin treatment. This activated cathepsin B-like enzyme had almost the same characteristics regarding molecular size, substrate specificity, dependence on chemical reagents, and Km values as intracellular cathepsin B. Sodium dodecylsulphate polyacrylamide gel electrophoresis followed by electroblotting with an antiserum against cathepsin B yielded inactive cathepsin B-like enzyme fractions which showed two immunoreactive bands with molecular masses of 40 and 28 kD, respectively. On the other hand, alkali treatment of the inactive cathepsin B-like enzyme fractions released a cysteine proteinase inhibitor with a molecular mass of 12 kD. These data suggest that these inactive cathepsin B-like enzymes in melanoma culture medium are present not only in the precursor form, but that they are also present as enzyme-inhibitor complexes, both of which can be activated enzymatically in vitro. PMID- 1422191 TI - Isomers of a marine diterpene distinguish sublines of human melanoma cells on the basis of apoptosis, cell cycle arrest and differentiation markers. AB - The action of the marine furanoditerpenes, spongiatriol (SP) and episopongiatriol (ESP), were compared in two sublines of human melanoma cells (MM96E and MM96L) derived from the same metastatic lesion. MM96E had higher tyrosinase activity and lower expression of alkaline phosphatase but was otherwise indistinguishable from MM96L. SP and ESP treatment of both cell lines for 72 h at cytostatic doses inhibited B8G3 expression and tyrosinase activity but had little effect on the expression of tyrosinase antigen. MM96L cells were affected more than MM96E. SP and ESP induced apoptosis in both cell lines, ESP causing dendritic morphology in a proportion of MM96L cells. SP induced a marked G2/M arrest in MM96E cells. SP and ESP together define subtle qualitative and quantitative differences in human melanoma phenoypes, possibly based on expression of a repertoire of neurotransmitter receptors. PMID- 1422192 TI - Regional distribution of common and dysplastic naevi in relation to melanoma site and sun exposure. A case-control study. AB - The frequency of melanoma (CMM), and of common and dysplastic naevi (CN and DN) in areas of skin chronically, intermittently and rarely exposed to UV light was investigated in 121 melanoma patients (30-50 years) and 310 controls. Both cases and controls had significantly more CN in intermittently exposed areas than in areas chronically or rarely exposed. The ratio of observed to expected number of CMM was also highest in intermittently exposed skin (1.3 compared to 0.8 in chronically exposed and 0.5 in rarely exposed areas). Thus, intermittent UV exposure seems to have the most potent 'naevogenic' as well as carcinogenic effect on melanocytes. Nineteen per cent of controls and 56% of cases had naevi fulfilling the clinical criteria for DN. The distribution pattern of DN was clearly different from that of CN and does not accord with the idea that UV light is a major aetiological factor for DN. The probability of CMM significantly increased with the degree of relative clustering of CN (p less than 0.05) and of DN (p less than 0.01). This co-variation of naevi and CMM over the body surface might be the result of the local insults to the melanocyte system caused by UV light and/or to the fact that naevi are precursor lesions of CMM. PMID- 1422193 TI - The usefulness of single and combined clinical characteristics for the diagnosis of dysplastic naevi. AB - A total of 761 melanocytic lesions were studied to elucidate the usefulness of clinical features for the diagnosis of dysplastic naevi. Characteristics associated with high (irregular border, irregular pigmentation), intermediate (black coloured areas, largest diameter greater than 0.5 cm, change of size, change of colour) and low diagnostic efficiency could be defined. Combinations of criteria had high sensitivities: at least one of the following four criteria was positive in 96% of the dysplastic naevi and in all melanomas with less pronounced clinical characteristics: irregular border, irregular pigmentation, greatest diameter greater than 0.5 cm, black coloured areas. A lesion is therefore unlikely to be a dysplastic naevus or a melanoma if all these criteria are absent. When change of size and change of colour were analysed in addition to the features mentioned above a sensitivity of 0.96 was found for at least two of these six criteria. At least three of these six criteria were observed in all melanomas with less pronounced clinical characteristics. However, a rather low specificity (0.19 for at least one of four positive criteria, 0.20 for at least two of six positive criteria) indicated that dysplastic and non-dysplastic naevi cannot be clinically differentiated with acceptable certainty. With less stringent histological criteria approximately twice as high specificities were found. Specificities were about twice as high in a subgroup of patients with at least one proven dysplastic naevus besides the lesion under diagnostic consideration. This facilitates the identification of individuals at risk of developing a melanoma. PMID- 1422194 TI - Outpatient surgical treatment of cutaneous melanoma. AB - From January 1988 to December 1989, 920 patients with pigmented cutaneous lesions, clinically diagnosed as suspected or certain cutaneous melanoma (CM), underwent excision under local anaesthesia as outpatients. Histological examination confirmed CM in 135 patients. Patients in this group whose initial excision was for biopsy purposes only (extending 1-2 mm beyond the lesion margin) underwent a subsequent radical excision (extending greater than or equal to 10 mm from the neoplastic margin). The second resection was carried out within 10 to 15 days of the first, on an outpatient basis if the thickness of the CM was less than or equal to 2 mm, and in hospital if it was greater than 2 mm. The clinical diagnosis proved correct in 88 cases (65%) where exeresis was the definitive surgical treatment. Outpatient surgery seems to be the best method for easing a workload dominated by the need to examine a growing number of pigmented skin lesions, without altering the prognosis for CM. PMID- 1422195 TI - Uptake of [131I]thiouracil in tumours of patients with disseminated malignant melanoma. A pilot study. AB - Previous studies on mice carrying melanoma have shown that 5-iodo-2-thiouracil (ITU) is accumulated in the tumours due to its specific incorporation into melanin during its synthesis. ITU is also selectively localized in murine melanoma metastases and in cultured human melanoma cells. Progressive formation of melanin is, however, a prerequisite for the incorporation. Four patients with disseminated melanoma were injected intravenously with 39-62 MBq [131I]TU. Blood and urine samples were gradually collected, and 3-7 days postinjection tumours were biopsied and examined by impulse counting. The patients were scanned with a gamma camera over the total body daily for 3-4 days. The radioactivity was rapidly excreted. Poor melanin pigmentation of the tumours and low proliferation rate (possibly induced by chemotherapy) decreased the uptake of radioactivity by the tumors, and no imaging was possible. One of the patients, however, had clearly progressive disease with darkly pigmented metastases which contained considerably higher levels of radioactivity than the surrounding skin. Calculations indicated that a doubling of the radioiodine dose would probably make visualization of the tumours possible. PMID- 1422196 TI - Thermal neutron capture therapy of malignant melanoma using 10B-monoclonal antibodies: in vitro and in vivo analysis. AB - We have established methods of targeting a sufficient number of 10B atoms on human melanoma cells to allow selective destruction of the cancer cells by thermal neutron irradiation. Thermal neutron capture therapy (NCT)1-3 requires the presence of at least 10(9) 10B atoms on each target cell for specific killing of that cell without injuring normal tissues. In order to accumulate an adequate number of 10B atoms on target cells, we first created an effective compound containing 12 atoms of 10B per molecule (10B12-chlorpromazine) and 10B-dopa analogue (10B1-paraboronophenylalanine). In the present study, about three molecules of our newly synthesized 10B12-compound were conjugated to an avidin molecule. The resulting 10B38.5-avidin compound can be specifically directed to human melanoma cells by biotinated monoclonal antibodies (MAbs) specific for the cells. We were able to accumulate 2.6 x 10(8) 10B atoms on a melanoma cell using this method. Cultured human melanoma cells treated with 10B-avidin-biotin-MAb (10B-AB-MAb) were selectively damaged by thermal neutron irradiation in vitro. This is the first study to indicate that thermal neutrons selectively damage target cells boronated by MAbs. PMID- 1422197 TI - Multipoint linkage mapping of the Emery-Dreifuss muscular dystrophy gene. AB - The clinical features to establish the diagnosis of X-linked Emery-Dreifuss muscular dystrophy (EMD) were recently redefined at the European EMD workshop in Baarn 1991. These criteria were used to select families from the literature and two new families for linkage analysis with the DNA markers F9, DX52, DXS15, F8C and DXS115. Recombinations are observed with the DNA markers F9, DXS52 and DXS15. No recombinations were found with F8C and DXS115. Multipoint linkage analysis indicates with a maximum location score of 73.9 that the EMD locus maps very close to F8C. PMID- 1422198 TI - A deletion including the brain promoter of the Duchenne muscular dystrophy gene is not associated with mental retardation. AB - A total of 161 unrelated Duchenne (DMD) and Becker muscular dystrophy (BMD) patients were screened for deletions in the brain promoter region of the dystrophin gene. Southern blot analysis using a probe for the brain promoter detected a deletion in this region in only one of the DMD families, in a patient with normal intelligence. This deletion also included the promoter of the muscle type dystrophin and the exons encoding the actin-binding and part of the spectrin like domains. Our data suggest that deletions in the brain promoter region are rare in DMD and are compatible with normal intelligence. PMID- 1422199 TI - Early onset autosomal dominant progressive muscular dystrophy presenting in childhood as a Becker phenotype--the importance of dystrophin and molecular genetic analysis. AB - We present two cases of autosomal dominant limb girdle muscular dystrophy in a father and son. Both presented in childhood with a classical Becker muscular dystrophy phenotype. The father had initially been informed that he would not have affected children. After the diagnosis of muscular dystrophy in the son, immunoblot analysis was performed on muscle and revealed normal dystrophin. The polymerase chain reaction did not show any deletions in the dystrophin gene, and the father's dystrophin gene was not passed to his son. These cases demonstrate that autosomal dominant muscular dystrophy may present in childhood, and that dystrophin and molecular genetic analyses should be performed when considering the diagnosis of childhood muscular dystrophy, even in the presence of a classical phenotype. PMID- 1422200 TI - Melas: an original case and clinical criteria for diagnosis. AB - We describe the full history and postmortem findings in one of the first identified cases of mitochondrial encephalomyopathy with stroke-like episodes (MELAS). To clarify diagnostic criteria, we analyzed 69 reported cases. The syndrome should be suspected by the following three invariant criteria: (1) stroke-like episode before age 40 yr; (2) encephalopathy characterized by seizures, dementia, or both; and (3) lactic acidosis, ragged-red fibers (RRF), or both. The diagnosis may be considered secure if there are also at least two of the following: normal early development, recurrent headache, or recurrent vomiting. There are incomplete syndromes in relatives of patients with the full syndrome and incomplete syndromes might also be encountered in sporadic cases. Some MELAS patients have features of the Kearns-Sayre syndrome (KSS) or myoclonic epilepsy with ragged-red fibers (MERRF), but none had the full KSS syndrome. In partial or confusing cases, analysis of mitochondrial DNA (mtDNA) may point to the correct diagnosis; however, not all patients with clinical MELAS have had the typical mtDNA point mutation and some patients with the mutation have clinical syndromes other than MELAS. PMID- 1422201 TI - Gene therapy: present situation and future prospects. AB - In this review, some of the most characteristic experimental approaches have been surveyed, using in vitro cultivated cell systems or animal models to achieve therapeutical gene treatment of severe monogenic diseases. Great advances have been made in the utilization of viral-mediated gene transfer as well as by direct DNA injection techniques to permit either stable insertion of a "correcting" gene into the chromosomes of a cell or a tissue or its penetration and activity as an episome. In most instances, long-term expression of the newly introduced genetic information could be obtained and certain genetic defects could be compensated for or corrected in cultivated cells or in vivo. Recent approvals on certain protocols concerning somatic gene therapy in humans indicate that the medical world is quite conscious of the importance of this new strategy. Certain ethical considerations are listed and discussed. PMID- 1422202 TI - Genetic counselling. PMID- 1422203 TI - Molecular forms of acetylcholinesterase in dystrophic (mdx) mouse tissues. AB - We analyzed the activity of acetylcholinesterase (AChE) and its molecular forms in the tissues of normal and dystrophic (mdx) mice, at different developmental stages. We studied the brain, the heart and the serum, in addition to four predominantly fast-twitch muscles (tibialis, plantaris, gastrocnemius and extensor digitorum longus (EDL)) and the slow-twitch, soleus muscle. We found no difference between mdx and control mice in the AChE activity of the brain and the heart. The skeletal muscles affected by the disease undergo active degeneration counterbalanced by regeneration between 3 and 14 weeks after birth. The distribution of AChE patches associated with neuromuscular junctions was abnormally scattered in mdx muscles, and in some cases (tibialis and soleus), the number of endplates was more than twice that of normal muscles. There were only minor differences in the concentration and pattern of AChE molecular forms during the acute phase of muscle degeneration and regeneration. After this period, however, we observed a marked deficit in the membrane-bound G4 molecular form of AChE in adult mdx tibialis, gastrocnemius and EDL but not in the plantaris or in the soleus, as compared with their normal counterparts. Whereas the amount of AChE markedly decreased in the serum of normal mice during the first weeks of life, it remained essentially unchanged in the serum of mdx mice. It is likely that this excess of AChE activity in serum originates from the muscles. A deficit in muscle G4 was also reported in other forms of muscular dystrophy in the mouse and chicken. Since it is not correlated to the acute phase of the disease in mdx and also occurs in genetically different dystrophies, it probably represents a secondary effect of the dystrophy. PMID- 1422204 TI - Dystrophin at the plasma membrane of human muscle fibers shows a costameric localization. AB - We studied the distribution of dystrophin at the sarcolemma of normal human muscle fibers using high resolution immunofluorescence and confocal laser scanning optical microscopy (CLSOM). We found that the dystrophin lattice is organized at the muscle plasma membrane in an array of thick bands interconnected by a finer network. The bands encircle the muscle fiber perpendicular to the long axis of the fiber and they matched the sites of attachment of the sarcomeres to the plasma membrane. Dystrophin co-localized with vinculin, and dystrophin and vinculin co-localized with alpha-actinin at the region of the I-band. Dystrophin may be one of the proteins involved in the linkage of the sarcomeres to the extracellular matrix. PMID- 1422205 TI - Purification of annexin I and annexin II from human placental membranes by high performance liquid chromatography. AB - Annexin I and annexin II were extracted from human placental membranes with ethylene glycol bis(beta-amino-ethyl ether)-N,N'-tetraacetic acid (EGTA) and purified by high-performance liquid chromatography by measuring their ability to inhibit phospholipase A2 activity in vitro. Neither protein was capable of binding to a DEAE-5PW HPLC column at neutral pH; however, they were resolved through binding to a Mono S column and passage through size-exclusion HPLC columns. Annexin I and its covalently linked dimer (36 and 66 kDa, respectively, by sodium dodecyl sulfate (SDS)-gel electrophoresis) reacted in one-dimensional immunoblots with monoclonal antibodies to annexin I and calpactin II, and with monoclonal and polyclonal antibodies to lipocortin I, confirming that annexin I, calpactin II, and lipocortin I are the same or closely related proteins. Milligram amounts of monomeric annexin I containing negligible amounts of the cross-linked dimeric annexin I were selectively isolated from placental membranes by using buffers containing the sulfhydryl reagent iodoacetic acid. Milligram amounts of cross-linked annexin I were selectively isolated when placental membranes were initially treated with buffers that did not contain iodoacetic acid and then extracted with Triton X-100, suggesting that sulfhydryl-dependent transglutaminase activity contributes to the selective isolation of this protein. A third phospholipase A2-inhibitory protein (35 kDa by SDS-gel electrophoresis) that reacted in immunoblots with monoclonal antibodies to calpactin I and annexin II, indicating their similar identity, was isolated. The procedure employed allows the rapid purification of annexins I and II in milligram amounts from placental membranes within 2 days. PMID- 1422206 TI - Purification of recombinant human secretory phospholipase A2 (group II) produced in long-term immobilized cell culture. AB - Recombinant human secretory phospholipase A2 (Group II) was expressed in long term culture of immobilized Chinese hamster ovary cells utilizing a continuous perfusion airlift bioreactor. The bioreactor was continuously perfused with cell culture medium supplemented with 5% fetal calf serum at an average flow rate of 5 liters/day for 30 days. Recombinant phospholipase A2, at concentrations ranging from 100 to 500 micrograms/liter, was purified to apparent homogeneity by an efficient two-step procedure involving a silica-based cation-exchange resin and hydrophobic interaction chromatography (greater than 65% recovery of phospholipase A2). The purified recombinant protein has an apparent molecular weight of 16 kDa, identical to that of purified human placental or synovial fluid phospholipase A2, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Application of the purified protein onto several different gel filtration columns resulted in elution of the protein at molecular weights corresponding to 3.1-4.7 kDa, suggesting an interaction of the protein with the column resins. However, analytical ultracentrifugation experiments revealed that the protein behaves as a monomer (13.8-14.2 kDa) over a protein concentration range of approximately 10 micrograms/ml to 5 mg/ml. With autoclaved Escherichia coli membranes as substrate, the recombinant protein has catalytic properties (pH optimum, effects of bovine serum albumin, sodium chloride concentration, and requirement for calcium) similar to those of the protein purified from human placenta. PMID- 1422207 TI - Rice cystatin: bacterial expression, purification, cysteine proteinase inhibitory activity, and insect growth suppressing activity of a truncated form of the protein. AB - A cDNA clone that encodes oryzacystatin, a cysteine protease inhibitor from rice, was isolated and expressed in Escherichia coli BL-21 (DE3) using an expression plasmid under the control of a T7 RNA polymerase promoter. The construct pT7OC 9b encoded a fusion protein containing 11 amino acid residues of the NH2 terminus of the bacterial protein phi 10 and 79 residues of oryzacystatin lacking 23 NH2 terminal residues of the wild-type protein. Recombinant oryzacystatin (ROC) constituted approximately 10% of the total bacterial protein mass and was purified in a single step by anion-exchange chromatography. The inhibitory activity of ROC toward papain (Ki = 3 x 10(-8) M) was comparable with that of the naturally occurring protein isolated from rice. Caseinolytic activity in midgut homogenates from seven species of stored product insects was inhibited from 18 to 85% by ROC, whereas the same activity was inhibited from 14 to 69% by the serine proteinase inhibitor phenylmethylsulfonyl fluoride. Midguts of stored product insects apparently contain both cysteine proteinases and serine proteinases, but the relative amounts vary with the species. When fed to the red flour beetle, Tribolium castaneum, 10 wt% ROC in the diet suppressed growth approximately 35% relative to that of the control group of insects. PMID- 1422208 TI - A new series of trpE vectors that enable high expression of nonfusion proteins in bacteria. AB - Expression of recombinant proteins in bacteria has facilitated the characterization of many gene products. However, the biochemical characterization of recombinant proteins is limited since the bacterially expressed proteins are often synthesized as fusion polypeptides. The presence of bacterial sequences in fusion proteins further limits the use of these proteins for generating antibodies since the bacterial sequences are also antigenic. We describe two new bacterial expression vectors based on the pATH series of plasmids. These vectors were made by precisely deleting all of the trpE coding sequences found in pATH. The new vectors have enabled us to express eukaryotic genes as nonfusion polypeptides. These altered plasmids can be used to insert any DNA sequence of interest through a multiple cloning site located just 3' of an ATG start codon. Protein expression is still under the control of the trp operon and is carried out at great efficiency when the bacteria are tryptophan deprived. Studies presented here test the expression system with neurofilament subunits, NF-L and NF-H. Large amounts of recombinant nonfusion proteins were produced. Also, a time course of induction shows that the production of the nonfusion proteins was under the control of the trp operon which is readily inducible after tryptophan starvation and addition of indoleacrylic acid. These vectors may be useful for the overexpression of many proteins in a form closely approximating their native state. PMID- 1422209 TI - Overproduction and purification of Bacillus subtilis DNA polymerase III. AB - The objectives of this work were to engineer the cloned polC gene encoding Bacillus subtilis DNA polymerase III for controlled overexpression in Escherichia coli and to devise a facile purification scheme permitting the large-scale production of pure recombinant polymerase. The translational signals of polC were restructured by expression cassette PCR (MacFerrin et al., 1990, Proc. Natl. Acad. Sci. USA 87, 1937-1941), and the modified gene was inserted into the expression plasmid, pKC30 (Rosenberg et al., 1983, in "Methods in Enzymology," Vol. 101, pp. 123-138, Academic Press, San Diego), under the strict control of the coliphage lambda pL promoter and its repressor, cI. When the system was derepressed at 32 degrees C, soluble DNA polymerase III accumulated at levels approximating 2% of total cellular protein. The recombinant protein was purified to greater than 99% purity by utilizing a tandem combination of Cibacron blue agarose, phenyl-Sepharose, and MonoQ FPLC chromatography. The properties of the purified recombinant protein were indistinguishable from those of native B. subtilis DNA polymerase III. PMID- 1422211 TI - The adenovirus E1A 243R protein purified from Escherichia coli under nondenaturing conditions is found in association with dnaK. AB - The adenovirus E1A 243R protein immortalizes primary cells in culture and induces part of the phenotypes required for transformation. It has also been shown to interact with a number of cellular polypeptides, including the product of the retinoblastoma gene. To understand more fully the molecular activities of the E1A 243R protein in association with these proteins as well as its role in the processes of cellular growth, we have developed a method for rapidly purifying this protein from genetically engineered Escherichia coli under nondenaturing conditions. The plasmid-encoded E1A protein, when expressed in a protease deficient mutant, is found to have the same length and amino acid sequence as that which is produced in a mammalian cell. The procedure for purifying the E1A 243R protein from bacteria relies primarily upon immunoaffinity chromatography and the use of a peptide comprising the epitope recognized by an E1A-specific antibody. Elution of the E1A protein under this condition allows for gentle isolation and a purity that ranges from 90 to 96%. However, without the addition of micromolar amounts of ATP prior to its elution from the antibody column, the E1A protein is found in association with an E. coli protein of 70 kDa. Immunoblot analysis with a specific antibody showed that this bacterial protein was the heat shock protein dnaK, which is known to have extensive homology with the hsp-hsc70 family of proteins in mammalian cells. Recognition of E1A by the dnaK protein may very well reflect a situation that also occurs between the mammalian heat shock proteins and the E1A 243R protein after adenovirus infection. PMID- 1422210 TI - Purification of the medium-chain/long-chain (COT/CPT) carnitine acyltransferase of rat liver microsomes. AB - A procedure for the purification of the rat liver microsomal carnitine octanoyltransferase (COT) that catalyzes the reversible formation of medium-chain and long-chain acylcarnitines from acyl-coenzyme A is described. The K0.5 for L carnitine is 0.6 mM and the K0.5 for both decanoyl-CoA and palmitoyl-CoA is 0.6 microM. The Vmax with decanoyl-CoA is approximately fourfold greater than the Vmax with palmitoyl-CoA. The enzyme is monomeric, sodium dodecyl sulfate polyacrylamide gel electrophoresis gives a molecular weight of 50,100, and molecular sieving gives a molecular weight of 54,300. Purified COT does not cross react with either antimitochondrial carnitine palmitoyltransferase or antiperoxisomal COT antibodies. It also does not form a covalent adduct when incubated with etomoxiryl-CoA. Microsomal COT is a different protein than either mitochondrial carnitine palmitoyltransferase or peroxisomal COT. PMID- 1422212 TI - Resolution of brewer's yeast pyruvate decarboxylase into multiple isoforms with similar subunit structure and activity using high-performance liquid chromatography. AB - A method for the purification of brewer's yeast pyruvate decarboxylase (EC 4.1.1.1) that resolves the enzyme into multiple active isoforms was developed. Seven activity fractions are resolved by DEAE HPLC chromatography. Among these fractions, three distinct subunit composition isoforms are apparent by sodium dodecyl sulfate-polyacrylamide gel electrophoresis: alpha 4, a homotetrameric holoenzyme consisting of the lower mass subunit; alpha 2 beta 2, a heterotetrameric holoenzyme consisting of lower and higher mass subunits; and beta 4, a homotetrameric holoenzyme consisting of the higher mass subunit. Beta 4 is a heretofore unreported form which may represent the unproteolyzed form of the enzyme. The Km and Vmax for the alpha 4 and beta 4 isoforms are identical within the limits of experimental error, as is their behavior vis-a-vis the allosteric regulator pyruvamide. All active isoforms exist as tetramers according to gel filtration analysis under native conditions. The purification has been successfully applied to pyruvate decarboxylase isolated from two different species of yeast and therefore is likely to be of general utility for purification of this enzyme from other yeast sources. Conditions under which all three isoforms demonstrate exceptional stability, making them amenable to prolonged physicochemical studies at 4 degrees C and even at room temperature are reported. PMID- 1422213 TI - A modified vector for the controlled high-level overproduction of staphylococcal protein A fusion proteins in the periplasm of Escherichia coli. AB - A vector encoding the Staphylococcal protein A was modified by cloning the spa gene, including its signal peptide-encoding sequence, downstream of the translation initiation sites of the phage lambda cro gene and under the control of the temperature-inducible phage lambda pR promoter. The expression from this construct was studied using the Escherichia coli phoA gene as a reporter gene after fusion to the spa gene. Determination of alkaline phosphatase activity, 1 h after temperature induction of expression at 42 degrees C, revealed an 800-fold increase over host strain background level. The presence of the alternating selectable markers on the described vector, pHEMa153, which are essential for efficient oligonucleotide-directed construction of mutations by the gapped duplex DNA method, allows the construction of recombinant and mutated forms of Staphylococcal protein A fusion proteins and efficient expression of spa gene fusions without changing the vector system. PMID- 1422214 TI - Purification of pancreatic cholesterol esterase expressed in recombinant baculovirus-infected Sf9 cells. AB - A cDNA clone encoding the entire coding sequence of rat pancreatic cholesterol esterase (bile salt-stimulated lipase) was subcloned into the Baculovirus transfer vector pVL1392 and used to co-transfect Spodoptera frugiperda (Sf9) insect cells with wild-type Autographa californica nuclear polyhedrosis virus (AcNPV) DNA. Two recombinant proteins (M(r) 74 kDa and 64 kDa) reactive with anti cholesterol esterase IgG were produced and secreted by the infected Sf9 cells in large quantities in a time-dependent manner. The 74-kDa protein was detectable in the cultured medium at the second day post-infection and increased progressively, reaching a level of 50 micrograms/ml of culture medium after 8 days. Amino terminal sequencing of this recombinant protein showed that the signal peptide of cholesterol esterase was correctly cleaved, resulting in the production of mature protein. The 64-kDa recombinant protein was not detected in the medium until Day 5 post-infection and accumulated to a level of 25 micrograms/ml at Day 8. Both the 74- and the 64-kDa cholesterol esterases were biologically active and hydrolyzed the artificial substrate p-nitrophenyl butyrate. Results of this study demonstrated that Baculovirus-infected Sf9 cells can be used for high-level expression of pancreatic cholesterol esterase. The recombinant enzyme will be useful for further characterization of this protein. PMID- 1422215 TI - A large-scale preparative electrophoretic method for the purification of pyridine nucleotide-linked dehydrogenases. AB - A large-scale preparative polyacrylamide gel electrophoresis (PAGE) method that uses a 1.5- or a 2.0-cm-thick slab gel has been developed for the purification of NAD-dependent dehydrogenases. With the 2.0-cm-thick gel, a maximum volume (up to about 160 ml) of enzyme sample was applied to a gel plate, resulting in the application of a large amount of protein and enzyme. After the electrophoretic run, the enzyme band on the gel was detected by activity staining and recovered from the gel by extraction with a fairly loose-fitting glass-Teflon homogenizer. NAD-dependent alanine dehydrogenase, leucine dehydrogenase, and glycerol dehydrogenase were purified in high yields (more than 80%) by the preparative PAGE method. The method can be carried out using a simple slab gel apparatus, which is modified from the conventional analytical apparatus for the purpose of preparative PAGE under conditions used for routine analytical runs. Thus, the method may be suitable for use in purifying NAD(P)-dependent dehydrogenases and many other enzymes after conventional chromatography such as dye-ligand affinity chromatography or ion-exchange chromatography. PMID- 1422216 TI - Purification of an active monomeric recombinant HIV-1 trans-activator. AB - A method for the purification of a truncated, biologically active human immunodeficiency virus type 1 (HIV-1) trans-activator (rTAT) from recombinant Escherichia coli is reported here. The purification steps utilized include mild extraction (French press), concentration by ammonium sulfate precipitation, chromatography in 8 M urea on an S-Sepharose fast-protein liquid chromatography column, and finally, resolution by C-4 reverse-phase high-performance liquid chromatography. After the final step, the rTAT is dried and stored under salt free conditions. Amino acid compositional analysis and N-terminal sequence analysis confirm that the purified protein is rTAT. Unlike other methods reported for purification of recombinant HIV-1 trans-activator, our protocol uses urea instead of guanidine HCl. The rTAT is fully soluble in buffered solutions at concentrations exceeding 10 mg/ml, migrates as a single 14 kDa species on both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) and two dimensional PAGE gels with a pI of 9.3 +/- 0.3. Additionally, the rTAT migrates as a monomer on size-exclusion chromatography columns under native conditions. Finally, purified rTAT exhibits trans-activator activity when introduced into appropriate reporter cells. Since rTAT is monomeric when tested by gel filtration, and yet exhibits biological activity, we conclude that the method of purification we have utilized is distinct from all other methods reported to date. PMID- 1422217 TI - High-level production of human alpha- and beta-globins in insect cells. AB - High-level production of human alpha- and beta-globins in cultured Spodoptera frugiperda (Sf-9) cells infected with recombinant baculoviruses is described. The expressed globins are produced to 70-140 mg protein/liter of cell culture or 5 10% of the total cellular protein. Two recombinant baculoviruses for alpha globin, H alpha and H beta alpha, differ in their construction in that the 5' untranslated region of the beta-globin gene is inserted 5' to the alpha-globin mRNA coding region in H beta alpha. This insertion results in a 40% increase in yield of alpha-globin over that of H alpha. Consistent with previous observations of the processing of recombinant proteins in Sf-9 cells, both alpha- and beta globins expressed in Sf-9 cells are correctly processed to remove the initiating methionine from the amino termini of the globins. Sequencing of the expressed globins in Sf-9 cells confirms their identity with globins purified from human normal adult hemoglobin. PMID- 1422218 TI - Expression and purification of the alpha and beta subunits of Drosophila casein kinase II using a baculovirus vector. AB - Two recombinant baculoviruses that express the alpha and beta subunits of Drosophila melanogaster casein kinase II, respectively, have been constructed. The expressed proteins are similar to the authentic Drosophila subunits in size and are recognized by antisera raised against the Drosophila holoenzyme. Extracts derived from cells infected with the alpha subunit-expressing virus display elevated casein kinase II activity in vitro. This activity is markedly enhanced in extracts of cells infected with both viruses, or when alpha and beta subunit containing extracts are mixed in vitro following lysis. Recombinant holoenzyme and the alpha subunit were purified to near homogeneity using phosphocellulose column chromatography. The specific activity of the purified recombinant holoenzyme was very similar to that of the native enzyme, and was fivefold higher than that of the purified free alpha subunit. The Stokes radius of the recombinant holoenzyme was estimated to be 50 A, a value similar to that reported for the native enzyme, whereas the alpha subunit demonstrated a Stokes radius of 26.5 A. Studies using sucrose density gradient centrifugation showed that, under conditions of high ionic strength, the quaternary structure of the purified holoenzyme was tetrameric (like the native enzyme), whereas the structure of the alpha subunit was monomeric. At lower ionic strength the recombinant holoenzyme had a significantly higher sedimentation coefficient, characteristic of the formation of filaments found for the native enzyme. Interestingly, the purified catalytic subunit also displayed a higher S value under conditions of low ionic strength, revealing the formation of alpha subunit aggregates. PMID- 1422219 TI - Partial amino acid sequence of potato solanidine UDP-glucose glucosyltransferase purified by new anion-exchange and size exclusion media. AB - Solanidine UDP-glucose glucosyltransferase (SGT) is involved in the biosynthesis of steroidal glycoalkaloids in potatoes. This enzyme is present at an extremely low level, is inherently unstable, and copurifies with the major storage protein patatin during isolation. We describe an improved method for isolating SGT from greening potato peel using two new chromatographic supports, Macro-Prep 50 Q anion-exchange and Superdex 75HR size exclusion media, under medium-pressure conditions at room temperature. The enzyme preparation was further resolved by SDS-PAGE and the proteins transferred to PVDF membrane (Immobilon-P). Two protein bands corresponding to active forms of SGT (36 and 37 kDa) were excised and cleaved with cyanogen bromide in trifluoroacetic acid. The resultant peptide mixtures were then separated by Tricine-SDS-PAGE and transferred to a PVDF membrane (Pro-Blott). The two major peptide bands observed in both digests (17 and 19 kDa) were sequenced. Identical N-terminal sequences were obtained from the 19-kDa peptides from both digests. PMID- 1422220 TI - Purification and biochemical characterization of recombinant rat liver phenylalanine hydroxylase produced in Escherichia coli. AB - Phenylalanine hydroxylase, important in phenylalanine metabolism in mammals, is regulated through short-term (activation) and long-term (induction) mechanisms. To help elucidate the structure-function relationships involved in the activation of this enzyme, we have isolated and characterized full-length cDNA clones to rat phenylalanine hydroxylase. Recombinant rat phenylalanine hydroxylase was placed into an expression vector in Escherichia coli. The enzyme has been purified to homogeneity and its physical and catalytic properties have been characterized. The molecular weight and the fluorescence emission spectrum of the recombinant enzyme were identical to those of the native enzyme. The recombinant enzyme could be activated by incubation with phenylalanine or lysolecithin or by phosphorylation, as is the rat liver enzyme. The extent of activation is the same as that for the native enzyme in each case except for phenylalanine, which activates the recombinant enzyme only 5- to 10-fold rather than the 15- to 30 fold activation observed with the native enzyme. The kinetic constants determined for the recombinant enzyme are also essentially the same as those reported for the native enzyme. We conclude that this enzyme is essentially identical to the native enzyme and should be very useful in the future study of this important hydroxylase. PMID- 1422221 TI - Immobilized metal ion affinity chromatography. AB - The introduction of immobilized metal ion affinity chromatography, directed toward specific protein side chains, has opened a new dimension in protein purification. This review covers the principles and practice of IMAC that can be performed under very mild, nondenaturing conditions. IMAC is particularly suitable for preparative group fractionation of complex extracts and biofluids, but can also be used in high-performance mode: "HP-IMAC." Single-step purifications of 1000-fold or more may allow isolation of a particular protein from crude extracts on a milligram or gram scale. With respect to separation efficiency, IMAC compares well with biospecific affinity chromatography, and the immobilized metal ion ligand complexes are more likely to withstand wear and tear than are antibodies or enzymes. The enormous potential of IMAC and related metal affinity techniques is only in the initial stages of being explored and exploited. Synthesis of IMA adsorbents, and various modes of performing IMAC are discussed and exemplified with selected applications. Advantages and disadvantages are listed. Effective means of counteracting the few undesirable effects that can occur are suggested. PMID- 1422222 TI - Purification of an active species of recombinant kappa-bungarotoxin. AB - The expression of kappa-bungarotoxin in Escherichia coli from a synthetic gene results in the production of multiple species of polypeptide. These include not only biologically active kappa-bungarotoxin but also a variety of inactive species, which include inactive monomers as well as disulfide-linked polymeric species. Identification of these species and their separation from the biologically active recombinant toxin is necessary for the use of the toxin in physiological and biochemical studies. This has been accomplished by a combination of ion-exchange and reverse-phase chromatography which results in a homogeneous toxin preparation. The active material produced is sufficient for many types of biological studies and for mutagenesis experiments directed at determining the structure function relationships of toxin interactions with the neuronal nicotinic acetylcholine receptor. In addition, the kappa-bungarotoxin produced in this manner has the distinct advantage over venom-purified kappa bungarotoxin of not being contaminated with other venom components which could potentially affect experimental observations. PMID- 1422223 TI - High-level expression and production of recombinant human interleukin-6 analogs. AB - We have constructed and analyzed different mutant forms of interleukin-6 (IL-6) expressed in Escherichia coli that can be divided into two groups. The first group contains four full-length IL-6 molecules that differ in the presence of cysteine residues involved in disulfide bridges. The second group contains 22 N terminal amino acid deletions in addition to the differences in the cysteine residues. The different IL-6 muteins were extracted and their expression levels and solubility were compared. We found that the production levels of IL-6 can be dramatically improved by deleting the first 22 N-terminal amino acids of the molecule. We have also found that the production of IL-6 containing the four cysteine residues is lower than the production of the mutant molecules that lack one or both pairs of cysteines. The yield of soluble and properly refolded IL-6 was the highest when the disulfide bond between the cysteines at positions 74 and 84 was present in the mutein form, which also lacked the 22 N-terminal amino acids. PMID- 1422224 TI - Expression and purification of the cytoplasmic tail of an endocytic receptor by fusion to a carbohydrate-recognition domain. AB - Gene fusion has been used to produce the cytoplasmic domain of an endocytic receptor. DNA sequences coding for the 52 COOH-terminal amino acids of the mannose receptor from human macrophages, including the 41-amino acid cytoplasmic tail, were fused to the codons specifying the carbohydrate-recognition domain (CRD) of rat mannose-binding protein. The fusion protein was expressed in Escherichia coli and purified in one step on mannose-Sepharose, making use of the carbohydrate-binding activity of the CRD. The tail peptide was released from the fusion protein using endoproteinase Arg-C. This method provides an alternative to chemical synthesis for the production of midlength peptides. PMID- 1422225 TI - Production, purification, and characterization of human recombinant IL-8 from the eucaryotic vector expression system baculovirus. AB - The cDNA for the human chemotactic interleukin, IL-8, was subcloned from a bacterial source into the eucaryotic vector expression system baculovirus. Recombinant human IL-8 (rhIL-8) was synthesized and secreted from Sf9 cells derived from Spodoptera frugiperda following infection of a recombinant virus harboring the full-length IL-8 structural gene. Infected Sf9 cells produced rhIL 8 in a range from 0.5 to 2.0 mg of rhIL-8/liter of postinfection cell culture media. The recombinant interleukin was purified (greater than 600-fold) to homogeneity using preparative HPLC. rhIL-8 retained all of the physical, immunological, and biochemical properties observed for the natural product, monocyte-derived IL-8. rhIL-8 was assessed for biological efficacy by three criteria: (a) ability to induce chemotaxis in human neutrophils, (b) ability to induce oxygen burst metabolism, and (c) ability to be recognized by purified rabbit antibody generated against monocyte-derived IL-8. Antibody generated against monocyte-derived IL-8 recognized rhIL-8 isolated during all stages of the purification protocol. rhIL-8 was strongly chemotactic for human neutrophils and exhibited a chemotactic index comparable to that reported for other strong chemotactic peptides. rhIL-8 was identified following sodium dodecyl sulfate polyacrylamide gel electrophoresis as a single silver-stained band having an estimated molecular weight of 9.2 kDa and displayed amino acid residue molar abundance homology predicted for the mature form of the interleukin. Baculovirus vector expression coupled to preparative HPLC proved to be a very efficient method for large-scale recombinant interleukin production. PMID- 1422226 TI - Expression and purification of recombinant and native calreticulin. AB - Calreticulin is a 60-kDa Ca(2+)-binding protein of the endo(sarco)plasmic reticulum membranes of a variety of cellular systems. The protein binds approximately 25 mol of Ca2+ with low affinity and approximately 1 mol of Ca2+ with high affinity and is believed to be a site for Ca2+ binding/storage in the lumen of the endo(sarco)plasmic reticulum. In the present study, we describe purification procedures for the isolation of recombinant and native calreticulin. Recombinant calreticulin was expressed in Escherichia coli, using the glutathione S-transferase fusion protein system, and was purified to homogeneity on glutathione-Sepharose followed by Mono Q FPLC chromatography. A selective ammonium sulfate precipitation method was developed for the purification of native calreticulin. The protein was purified from ammonium sulfate precipitates by diethylaminoethyl-Sephadex and hydroxylapatite chromatography procedures, which eliminates the need to prepare membrane fractions. The purification procedures reported here for recombinant and native calreticulin yield homogeneous preparations of the proteins, as judged by the HPLC reverse-phase chromatography and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Purified native and recombinant calreticulin were identified by their NH2 terminal amino acid sequences, by their Ca2+ binding properties, and by their reactivity with anticalreticulin antibodies. PMID- 1422227 TI - Construction of a high-copy "ATG vector" for expression in Escherichia coli. AB - We report the construction of an inducible, high-copy plasmid for the expression of foreign proteins in Escherichia coli. This plasmid, pPB1, combines the trc promoter, beta-galactosidase translation start site, and polylinker of pKK233-2 with the origin of replication region of pUC19. Replacement of the origin of replication of pKK233-2 results in a threefold increase in plasmid copy number of pPB1 compared with pKK233-2. Subclones of the cDNA for rabbit muscle fructose-1,6 bisphosphate aldolase (E.C. 4.1.2.13) in the two expression plasmids exhibit a comparable difference in copy number. An increase in protein expression measured by SDS-PAGE and aldolase specific activities reflects the increased copy number. Specific activities of aldolases in bacterial extracts differ approximately sixfold between the two expression plasmids in E. coli JM83. Aldolase A can compose up to 40% of the total protein in E. coli JM83 when expressed in pPB1, from which more than 100 mg of purified enzyme can be obtained per liter culture. PMID- 1422228 TI - Overexpression and purification of the separate tryptophan synthase alpha and beta subunits from Salmonella typhimurium. AB - To obtain high levels of expression of the free alpha and beta subunits of tryptophan synthase from Salmonella typhimurium, we have used two plasmids (pStrpA and pStrpB) that carry the genes encoding the alpha and beta subunits, respectively. The expression of each plasmid in Escherichia coli CB149 results in overproduction of each subunit. We also report new and efficient methods for purifying the individual alpha and beta subunits. Microcrystals of the beta subunit are obtained by addition of polyethylene glycol 8000 and spermine to crude bacterial extracts. This crystallization procedure is similar to methods used previously to grow crystals of the S. typhimurium tryptophan synthase alpha 2 beta 2 complex for X-ray crystallography and to purify this complex by crystallization from bacterial extracts. The results suggest that purification by crystallization may be useful for other overexpressed enzymes and multienzymes complexes. Purification of the alpha subunit utilizes ammonium sulfate fractionation, chromatography on diethylaminoethyl-Sephacel, and high-performance liquid chromatography on a Mono Q column. The purified alpha and beta subunits are more than 95% pure by the criterion of sodium dodecyl sulfate gel electrophoresis. The procedures developed can be applied to the expression and purification of mutant forms of the separate alpha and beta subunits. The purified alpha and beta subunits provide useful materials for studies of subunit association and for investigations of other properties of the separate subunits. PMID- 1422229 TI - Thyrotropin modulation of epidermal growth factor (EGF) binding to receptors on cultured thyroid cells. AB - Previous studies had shown that epidermal growth factor (EGF) will stimulate growth of cultured thyroid cells in vitro, and TSH will stimulate total assayable EGF receptor in cultured porcine thyroid cells. In this study, we report the effect of TSH on EGF binding to human thyroid cells. Addition of bTSH (1 mU/mL) in binding buffer during receptor assay stimulated specific EGF binding to cells, with an increase of 44% observed over the control after 1 h incubation at 37 degrees C. Affinity crosslinking of the [125I]EGF-receptor complex showed a single labeled band with molecular size of 170 kD. No additional band was detected in the presence of TSH. Preincubation of cells with chloroquine, which inhibits lysosomal degradative enzyme activity, caused a continuous accumulation of bound EGF over a 4 h study period at 37 degrees C, and TSH stimulated an increase in internalized EGF. In the presence of chloroquine, total specific bound EGF was linearly correlated to incubation time up to 4 h and can be expressed as Bound = slope*time+intercept (time0) Addition of TSH during the binding assay significantly increased the value of the slope when compared to control (p < 0.002). The rate at which prebound [125I]EGF was released into medium was not affected by the presence of TSH, indicating that TSH-enhanced binding may not be attributed to a reduction in EGF degradation. Coincubation of thyroid cells with EGF at 0 and 1 ng/mL and increasing concentrations of TSH (0 10 mU/mL) indicated that EGF stimulated thymidine incorporation, although TSH failed to synergistically enhance EGF-stimulated cell growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422230 TI - Peroxidase and coupling activities of thyroid peroxidase in benign and malignant thyroid tumor tissues. AB - The coupling activity of thyroid peroxidase (TPO) in thyroid glands from patients with benign adenoma, papillary carcinoma, and diffuse goiter (Graves' disease) was measured for the first time, in addition to the peroxidase activity of these tissues. The peroxidase activity of TPO in the mitochondria-microsomes fraction was measured with guaiacol or iodide as the second substrate. In the case of papillary carcinoma, the mean protein-based specific activity obtained by the guaiacol assay was about 1/7 of that of diffuse goiter. The iodide oxidation activity of carcinoma was very low, about 1/25 [corrected] of that in diffuse goiter and 1/70 of that in adenoma. The peroxidase activity in adenoma was almost similar in the guaiacol oxidation assay and approximately one half in the iodide oxidation assay as compared with that in diffuse goiter. There was a close correlation between the guaiacol and iodide oxidation assays in individual patients with adenoma and diffuse goiter, but not in patients with papillary carcinoma. The coupling activity of TPO was measured with thyroglobulin purified from pooled toxic diffuse goiters and chemically iodinated to contain little additional T3 and T4. The specific coupling activity of TPO in mitochondria microsomes from carcinoma was significantly lower (about 1/5) than that of diffuse goiter, and the activity in adenoma was not significantly different (about 1/2) from that of diffuse goiter. The data of coupling activities has a close correlation with that of peroxidase activities in individual patients with adenoma but not in patients with carcinoma. Based on these findings, the qualitative abnormality of TPO and its relation to the cold 123I scintigram in thyroid tumors are discussed. PMID- 1422232 TI - Relapse of Graves' disease following development of a pheochromocytoma. AB - Catecholamines stimulate thyroid hormone synthesis as well as release of thyroid hormone and cause immunologic disturbances that possibly contribute to the manifestations of Graves' disease. This has led to repeated speculations about the possible role of catecholamines in the initiation and maintenance of hyperthyroidism. We describe a patient with Graves' disease who was treated with antithyroid drugs for 2 years. After withdrawal of antithyroid drugs, the patient was in remission for 5 years. After the antithyroid drug treatment and the long remission, the probability of relapse of Graves' disease was very low. Nonetheless, a relapse did occur. Two years after subtotal thyroid resection, further investigation because of persistent hypertension revealed a pheochromocytoma. Retrospective anamnestic data suggest that this pheochromocytoma had been present 2 years before the patient's relapse of Graves' disease. This sequence of diseases has not been described previously. The low probability for a Graves' disease relapse in this patient and the association of this patient's relapse with the manifestation of a pheochromocytoma suggest a possible etiologic role of excess catecholamine production in the relapse of Graves' disease. PMID- 1422231 TI - Significance of antibodies reactive with a 64 kDa eye muscle membrane antigen in patients with thyroid autoimmunity. AB - SDS-polyacrylamide gel electrophoresis and Western blotting for antibodies reactive with a 64 kDa protein in pig eye muscle membrane was carried out in patients with lid lag and retraction, but no other signs of ophthalmopathy, associated with thyroid disease or nonimmunologic goiter and in patients with Graves' hyperthyroidism without ophthalmopathy who were studied prospectively to determine the relationship of eye muscle antibodies to clinical features of the ophthalmopathy as they appeared in this group of predisposed patients. Seventy one percent of euthyroid patients with lid lag and retraction but no established ophthalmopathy had detectable serum antibodies to a 64 kDa eye muscle membrane protein. Much smaller proportions had antibodies to proteins of other MW. In normal subjects with previously detectable antibodies to a 64 kDa protein, serum titers, determined by carrying out immunoblotting at serum dilutions of 1:25 1:6400, were low (< or = 1:100) in all cases tested. On the other hand, titers were higher (1:200-1:6400) in 16 of 22 patients with established ophthalmopathy and in 5 of 7 patients with lid lag and retraction tested. Titers tended to be lower in patients with ophthalmopathy of > or = 3 years duration than in those of < or = 1 year duration. Antibody titers were low (1:25) in 6 of 7 patients with Graves' hyperthyroidism without evident eye disease tested. Antibodies to a 64 kDa eye muscle membrane protein were predictive of the development of ophthalmopathy in patients with Graves' hyperthyroidism studied prospectively for periods of 8-42 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422234 TI - Diagnosis and management of Graves' disease in pregnancy. AB - Most of the hyperthyroidism seen in association with pregnancy is Graves' disease. The best treatment is prevention. For most patients there is an opportunity to treat the hyperthyroidism decisively with radioiodine or surgery before the patient becomes pregnant. Pregnancy complicated by hyperthyroidism is often a consequence of the conscious decision to treat hyperthyroidism in women in the childbearing years with antithyroid drugs. Propylthiouracil (PTU) is the preferred treatment for hyperthyroidism in pregnancy, but it does cross the placenta and can induce fetal goiter, with mental and physical retardation. Hence, the lowest possible PTU dose should be used. One should aim for high normal or slightly elevated thyroid function in the mother. Patients should be followed at 3-week intervals if progress is satisfactory, more often otherwise. Thyroid function should be monitored by the free T4 assay. PTU dosage should be reduced progressively in anticipation of the customary steady amelioration in the hyperthyroidism that occurs in later stages of pregnancy. Since pregnant hyperthyroid patients are sometimes irresponsible and continue PTU without supervision, PTU prescriptions should be limited to the amount required for the time until the next scheduled visit. For about one third of patients, PTU can be discontinued in the second half of the pregnancy. After the pregnancy is terminated, persistent or recurrent hyperthyroidism should be treated definitively to prevent another episode of pregnancy complicated by hyperthyroidism. PMID- 1422233 TI - Fetal thyroid function. AB - Cordocentesis has permitted the study of fetal thyroid function in utero. In normal fetuses, fetal TSH, TBG, and thyroid hormone concentrations increase progressively throughout intrauterine life. Fetal TSH concentrations are always high compared to nonpregnant adult values. TBG concentrations reach adult levels at term. TT4 and FT4 concentrations reach adult levels at approximately 36 weeks gestation, but TT3 and FT3 are always below adult concentrations. There are no significant associations between fetal and maternal concentrations of TSH, TBG, or thyroid hormones. The maternal administration of TRH from at least 25 weeks gestation stimulates the fetal pituitary gland to produce TSH. The response is rapid, unrelated to gestational age, and much greater than that of the mother. These findings suggest that in intrauterine life there is independent and autonomous maturation of the pituitary, thyroid, and liver. The fetal pituitary is able to respond to the maternal administration of TRH and appears to be more sensitive than in the adult. In small-for-gestational-age fetuses, the concentrations of TSH are higher and the concentrations of TT4 and FT4 are lower than in appropriately grown fetuses. The degrees of elevation of TSH and fall in thyroid hormones are significantly related to the degree of fetal hypoxemia and acidemia, respectively. Although the low concentrations of thyroid hormones may have some beneficial effects by reducing oxygen requirements, they may adversely affect brain development. PMID- 1422235 TI - The fetus in maternal hyperthyroidism. AB - A recent article in the New England Journal of Medicine reported the successful diagnosis and treatment of fetal goitrous hypothyroidism in a mother with Graves' disease. The fetus is being recognized as an important patient in its own right in terms of thyroid disease. The fetal thyroid system develops independently of the normal maternal thyroid axis. Presence of feedback suppression of TSH by T4 has been demonstrated in a 35-week fetus. Information learned from congenital hypothyroidism suggests that lack of fetal thyroid hormones may have a negative impact on the developing fetal brain with lack of normal myelination. It is uncertain at what gestational age the fetus and the developing central nervous system become adversely affected by thyroid hormone deficiency. Since congenital hypothyroidism is sporadic and since there is no current method for easily screening all pregnancies for hypothyroidism, the thrust in fetal diagnosis and therapy has been in those pregnancies suspected of having a hypothyroid fetus when a fetal goiter is detected by ultrasonography or in a hyperthyroid mother who may be on antithyroid therapy. Intraamniotic injections of L-thyroxine have proven successful for fetal therapy. Amniotic fluid TSH may prove useful in the diagnosis and treatment of a hypothyroid fetus. Previous studies have suggested that the period of thyroxine dependency of the fetal central nervous system is limited predominantly to the last 4-8 weeks of gestation. Fetal hyperthyroidism due to transplacental transmission of thyroid-stimulating immunoglobulins may occur in a mother with a history of hyperthyroidism due to Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422236 TI - Immunosuppressive treatment of Graves' ophthalmopathy. AB - Glucocorticoids and retrobulbar irradiation are the most employed immunosuppressive treatment modalities in Graves' ophthalmopathy. The response rate is approximately 60%. Efficacy is good for improvement of appearance and visual acuity, moderate for correction of extraocular muscle dysfunction, and poor for reduction of proptosis. Immunosuppression seldom cures the eye disease. Its main advantage is to stabilize the eye disease by inactivating the inflammation of orbital tissues, thereby permitting corrective eye surgery to be performed at an earlier time. Future developments in immunosuppression aim at reduction of side effects and enhancement of efficacy. Alternative treatment schedules (e.g., methylprednisolone pulses, intravenous immunoglobulin) may have equal efficacy but less side effects than classic high-dose oral steroids. Efficacy can be improved by restriction of immunosuppression to patients with active eye disease who are more likely to respond. Disease activity might well be the main determinant of therapeutic outcome of immunosuppression in Graves' ophthalmopathy. PMID- 1422237 TI - Classification of eye changes of Graves' disease. PMID- 1422238 TI - Variations in thyroid hormone transport proteins and their clinical implications. AB - Variations in major thyroid hormone transport proteins may be inherited or acquired and may be associated with changes in serum concentration of the proteins or their affinity for thyroid hormones. These variations most frequently involve thyroxine-binding globulin (TBG), but changes in transthyretin and albumin are also observed. The consequent alteration of thyroid hormone-binding capacity in serum is associated with variations in total thyroid hormone concentration. Increased serum total thyroid hormone levels are found in subjects with TBG excess, familial dysalbuminemic hyperthyroxinemia, and transthyretin associated hyperthyroxinemia. Conversely, diminished serum thyroid hormone values are observed in subjects with TBG deficiency, and decreased concentration or affinity of transthyretin and albumin is not associated with variations in serum concentrations of thyroid hormones. The transport protein-associated variations in serum total thyroid hormone concentrations do not reflect a change in thyroid status. Euthyroidism can be easily established in subjects with transport protein abnormalities by the normal free thyroid hormone and TSH concentrations. It is, however, crucial to select methods for free thyroid hormone measurement that are not affected by abnormalities of transport proteins. Some assays, such as the analog method, often provide artifactual and misleading results, which may lead to inappropriate and even detrimental treatments. The evolutionary advantage of TBG (and albumin) in terms of thyroid homeostasis still remains to be elucidated. PMID- 1422239 TI - Thyroid hormone suppressive therapy of sporadic nontoxic goiter. AB - Thyroid hormone has been used to reduce the size of sporadic nontoxic goiter since 1894. Noncontrolled clinical studies suggest that about two thirds of goiters respond to therapy, and a recent randomized clinical trial confirms the efficacy of suppressive therapy for sporadic nontoxic goiter. Efficacy is at least partly correlated with suppression of pituitary TSH production, response is usually evident by 3 months, relapse occurs when therapy is withdrawn, and nodular goiters may be less responsive than diffuse goiters. Some, but not all, series suggest that postoperative use of thyroid hormone suppressive therapy prevents recurrence of benign goiter. Three recent randomized trials suggest that thyroid hormone administered for 6 months to 3 years does not reduce the size of solitary thyroid nodules. About one third of nodules regressed in both treatment and placebo groups. Long-term studies are needed to define the effects of thyroid hormone suppressive therapy on the growth of goitrous lesions based on their underlying pathophysiology. PMID- 1422240 TI - Prenatal diagnosis and caring. AB - Although the science of prenatal diagnosis is rapidly expanding, the art of caring for these patients is poorly understood and taught. Prenatal diagnosis programs must acknowledge the psychosocial consequences of electing to undergo prenatal testing, receiving either normal or abnormal test results, and choosing to continue or terminate a pregnancy with an identified fetal defect. There are suggestions from the literature of interventions to assist families under these circumstances (Table 3). Prospective studies of patient adaptation are needed; however, on the basis of the retrospective studies and common sense, a reasonable plan for patient support and care can be established. Prenatal diagnosis programs must demand not only excellent medical knowledge and technical expertise but also compassionate and continued care for the patient, her partner, and family. PMID- 1422241 TI - Women's health care: rights and responsibilities. AB - We recently participated in efforts to implement community-based women's health programs in regions of the world that are undergoing broad reforms as one form of government is replaced by another. In the course of these activities, we have had reason to review the rich and voluminous literature on the pivotal contributions by patients, providers, and society that result in optimal health for women. This article reflects our perspective of that literature and a framework to achieve that goal. PMID- 1422242 TI - Specialists and generalists in obstetrics and gynecology: conflicts of interest in referral and an ethical alternative. AB - Referral patterns of physicians have a direct impact upon the care of patients, particularly in obstetrics and gynecology. The choice of referral is influenced by the history of specialization, physician altruism, and intricate patterns of financial conflicts of interest. The conflicts of interest are further obscured by the lack of clear definition of roles and responsibilities for generalist, specialist, and subspecialist. Alternate patterns for referral based on financial incentives or directed referral care plans are reviewed to examine the potential conflicts of interest. An ethics-based format for referral is outlined to address these conflicts of interest. PMID- 1422243 TI - Maternal mortality and morbidity in the developing world: personal reflections and a profession's commitment. PMID- 1422244 TI - The effects of woman abuse on health care utilization and health status: a literature review. AB - Estimates of the physical abuse of women by husbands or boyfriends in the United States range from 85 per 1000 couples to 113 per 1000 couples per year. Victims of abuse are much more likely than nonvictims to have poor health, chronic pain problems, depression, suicide attempts, addictions, and problem pregnancies. Abused women use a disproportionate amount of health care services, including emergency room visits, primary care, and community mental health center visits. Despite its high prevalence and the disproportionate use of health care services it causes, woman abuse is rarely recognized by health care providers. Even when the abuse is recognized, health care professionals often provide inappropriate or even harmful treatment. Because many abused women pass through the health care system, it is important that providers learn how to identify those who are abused, treat all the effects of the abuse, and make appropriate referrals. PMID- 1422245 TI - Premenstrual syndrome. PMID- 1422247 TI - Mammography lexicon. PMID- 1422246 TI - Disabled women. PMID- 1422249 TI - The case of Thomas Crane: recommendations in Ombudman's report. PMID- 1422250 TI - Elder abuse? Nurse abuse? Whose problem is this anyway? PMID- 1422251 TI - The rate of tonsillectomies in Saskatchewan. PMID- 1422252 TI - Living wills: a role in health care today? PMID- 1422253 TI - Ethical perspectives on client care. PMID- 1422254 TI - AIDS: essentials of AZT for nurses. PMID- 1422255 TI - Registered nurses: dispelling the myths. PMID- 1422256 TI - Regulation of interleukin 4 production and of interleukin 4-producing cells. AB - Interleukin 4 (IL-4) is a cytokine with a broad range of functions on immune cells including the stimulation of IgE synthesis by B cells. IL-4 is synthesized by freshly isolated T cells following appropriate stimulation with either lectins or antibodies against selected surface antigens. IL-4 production has also been observed by freshly isolated FceR+ non-T, non-B cells. With T cell clones, IL-4 is produced by clones of the Th2 and Th0, but not of the Th1 type. The molecular basis for restricted cytokine production by such clones as well as the signals responsible for differentiation into either phenotype are only at the beginning to be understood. PMID- 1422257 TI - Human TH1 and TH2 subsets: regulation of differentiation and role in protection and immunopathology. AB - A large body of evidence has accumulated suggesting the existence of human TH1 and TH2 subsets, reminiscent of those described for mouse T cells. Human TH1 cells develop in response to intracellular bacteria and viruses, do not provide help for IgE synthesis and are cytolytic. Human TH2 cells develop in response to allergens and helminth components, provide help for IgM, IgG, IgA, and IgE synthesis and lack cytolytic potential. The cytokine profile of 'natural' immunity (high IFN-gamma and no IL-4 production) evoked by intracellular bacteria and viruses that activate both macrophages and NK cells, probably determines the phenotype of the subsequent specific TH1 response. Absence or low concentration of IFN-gamma and early production of IL-4 by non-T cells or by T cells themselves, that occur in response to allergens and helminth components, probably favor the development of TH2 cells. TH1 and TH2 cells play different roles not only in protection against exogenous offending agents, but also in immunopathology. TH1 cells are involved in contact dermatitis, organ-specific autoimmunity and allograft rejection. TH2 cells are responsible for the initiation of the allergic cascade. PMID- 1422259 TI - Effect of antigens from Nippostrongylus brasiliensis and cytokines on the ongoing IgE synthesis in vitro. AB - The modulation of an ongoing IgE-mediated immune response induced by the infection of mice with the nematode Nippostrongylus brasiliensis (N.b.) was investigated in vitro. In previous experiments antigens derived from the homogenate of adult worms (WH) and third stage larvae (LH) were characterized by immunoblotting. Our results demonstrate that only antigens of the WH were recognized by IgE antibodies. The effect of worm antigens and cytokines (IL-2, IL 4, IL-5, IFN gamma) on the IgE and IgG synthesis in different culture systems was studied. The IgG synthesis of B cells was stimulated by WH or WH/cytokines. The IgE production of B cells was enhanced only by WH/cytokines or when T cells were present. Individual antigen fractions (WH 5, 8, 9, 10, 13) increased the IgE production, which was enhanced in the presence of IL-4 2- to 3.5-fold) but had no significant effects on the IgG production. PMID- 1422258 TI - Inflammatory cytokines and enzymes in synovial fluid of patients with rheumatoid arthritis and other arthritides. AB - Cytokines and lysosomal enzymes, which are produced by inflammatory cells, play a role in inflammation. We have found that synovial fluid (SF) in rheumatoid and septic arthritis contained a large number of white blood cells (WBCs) and high levels of cytokines and enzymes, while in contrast the SF of osteoarthritis and traumatic arthritis did not contain significant amounts. Measurements of WBCs, cytokines and enzymes in SF are useful for evaluating clinical disease activity. Assays for WBCs and enzymes are simple and rapid when compared to those for cytokines. PMID- 1422260 TI - Immunochemical properties of anti-DNA antibodies in the sera of patients with Escherichia coli bacteremia. AB - To assess the role of infection in anti-DNA antibody production, the DNA-binding activity of sera from patients with Escherichia coli bacteremia was analyzed. Among 8 patients with bacteremia documented by blood culture, 5 demonstrated increased levels of antibodies to single-stranded DNA from E. coli as measured by enzyme-linked immunosorbent assay. Sera from these patients also reacted with single-stranded DNA from other bacterial and mammalian species as well as certain synthetic polynucleotides including poly-dT and poly-dC. The isotype distribution of these antibodies and their avidity as assessed by competition enzyme-linked immunosorbent assay resembled, moreover, responses of patients with systemic lupus erythematosus. These results suggest that, during the course of infection with E. coli, some patients may produce antibodies with immunochemical properties similar to those arising in systemic lupus erythematosus. PMID- 1422261 TI - Characteristics of long-term human thyroid peroxidase autoantibody secretion in scid mice transplanted with lymphocytes from patients with autoimmune thyroiditis. AB - We have explored scid mice as an in vivo model to study lymphocyte function and autoantibody production in patients with autoimmune thyroiditis and thyroid peroxidase (hTPO) autoantibodies. Patient's peripheral blood mononuclear cells (PBMC) were transplanted into scid mice via intraperitoneal injections and human immunoglobulin G (hIgG) and thyroid autoantibody levels in the murine sera were monitored for a minimum of 3 months after transplantation. Human IgG reached maximum serum levels of > 3,000 micrograms/ml (mean +/- SEM = 1,199 +/- 354 micrograms/ml) after an average of 6.5 weeks. In reconstituted mice (hereafter named At-Scid-hu) substantial titers of anti-hTPO of up to 0.51 (ELISA index, normal range < 0.02) were observed over a period of 1-2 months, followed by a gradual decline. Immunization of AT-Scid-hu mice with immunogenic, recombinant human hTPO (rec-hTPO) failed to enhance hTPO-Ab levels. Furthermore, there was no correlation between the magnitude of human IgG in the murine serum and concomitant levels of anti-hTPO. Murine thyroid function was unaffected by the transplantation of PBMC, as evidenced by normal serum thyroxine (T4) levels, and lack of specific pathologic changes in the thyroid. These data indicate, for the first time, the potential for longer-term human thyroid autoantibody secretion in the scid mouse reconstitution model allowing for further investigation of the regulatory factors inpinging on the human B cells surviving in the murine environment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422262 TI - Expression and thrombin cleavage of Poa p IX recombinant allergens fused to glutathione S-transferase. AB - The high-level expression and purification of Poa p IX recombinant grass pollen allergens were examined utilizing a modified pGEX plasmid, designated as pGEX 2T 1. This vector permits frame-1 ligation of lambda gt11 cDNA inserts and cleavage of the recombinant allergenic protein from the fusion partner glutathione S transferase. The expression of the fusion proteins in water-soluble form varied among the transformants of the same bacterial strain and also between different host strains. Purification of the fusion proteins by affinity chromatography employing glutathione agarose gel revealed that proteases in the bacterial lysate bound to the gel and were co-eluted with the fusion proteins. These proteases, which specifically degraded the recombinant proteins to varying degrees, were inhibited by both of the inhibitors, phenylmethylsulfonyl fluoride and aprotinin. Cleavage by thrombin of the fusion proteins indicated that the structure of the individual protein affected the thrombin accessibility to the cleavage site. Increased concentration of thrombin partly compensated this effect, but resulted in a broader specificity of the enzyme. By contrast, cleavage of the fusion protein when it was still attached to the glutathione gel was convenient and led to purification of the product devoid of proteolytic activity. Since almost all the recombinant allergens have been cloned in lambda gt11 vector, the pGEX 2T-1 vector reported herein will facilitate the synthesis, purification of the corresponding allergenic proteins or their peptides in soluble and biologically active forms. PMID- 1422263 TI - Pharmacological modulation of the late eosinophilia induced by antigen in actively sensitized rats. AB - The intrathoracic injection of ovalbumin (12 micrograms/cavity) into actively sensitized rats led to a long-lasting eosinophil recruitment, which appeared 24 h after stimulation. In this study, pharmacological antagonists were used in order to evaluate the potential involvement of arachidonic acid metabolites and PAF acether in the pleural eosinophil accumulation by antigen. Administration of the cyclooxygenase inhibitor indomethacin (2 mg/kg, i.p.), 1 h before the antigen challenge, failed to modify the 24-hour eosinophilia. In contrast, the dual cyclooxygenase and lipoxygenase inhibitor BW 755C and the more selective inhibitor BW A4C (5 and 10 micrograms/cavity, i.t.), injected 1 h before the antigen, were effective. Similarly, the PAF-acether antagonists BN 52021 and WEB 2086 (20 mg/kg, i.p.) abrogated the eosinophil accumulation, which was also sensitive to the topical treatment with the glucocorticoid dexamethasone (5 and 10 micrograms/cavity). Our findings suggest that the antigen-induced eosinophil mobilization is dependent on lipoxygenase derivatives and PAF-acether, but not on prostaglandins. PMID- 1422264 TI - Expression of birch pollen-specific IgE-binding activity in seeds and other plant parts of birch trees (Betula verrucosa Ehrh.). AB - Dot immunoblotting of crude extracts of various aerial parts of birch trees, using patient serum rich in birch pollen IgE, showed IgE-binding activity in leaves, buds, twigs, seeds, bark, and old male catkins. Seed extracts analysed by SDS-PAGE, electroblotting to nitrocellulose and immune detection using isotope conjugated anti-IgE verified the presence in seeds of an IgE-binding protein of an approximate molecular weight of 12 kD, distinct from the major allergen (molecular weight 17 kD) of Betula verrucosa pollen. The allergen of birch seeds was readily leachable from the seeds. Many of the birch plant part extracts were active in RAST inhibition using birch pollen RAST discs, but showed low potency relative to the allergenicity of birch pollen allergens. PMID- 1422265 TI - Differentiation of coeliac disease and other malabsorption diseases using specific serum antigliadin IgG subclass profiles and IgA1 levels. AB - The differential diagnostic potential of serum gliadin-specific IgG subclass antibodies was assessed by comparing the antigliadin IgG1, 2, 3, 4 profile at different stages of coeliac disease with that of gastro-intestinal infection and also conditions associated with increased intestinal permeability. The IgG subclass profile of untreated coeliac disease was found to be the same as in healthy controls (IgG1 approximately IgG2 > IgG3 > IgG4), with only the magnitude of the individual subclass responses being increased in coeliac patients. Coeliac adults and children on gluten-free diets had different antigliadin IgG subclass profiles with IgG2 being elevated. Increased intestinal permeability or recent gastro-intestinal infection did not alter the antigliadin subclass profile from that observed in healthy individuals. Assessment of the diagnostic potential of antigliadin IgA1 and IgG1-4 measurements in screening for coeliac disease demonstrated that measurement of subclasses of gliadin-specific IgA and IgG was less sensitive and specific compared with the combined use of total antigliadin IgA and IgG. Therefore it is suggested that IgG subclasses should not be used for routine screening for coeliac disease. PMID- 1422266 TI - SO2-induced enhancement of inhalative allergic sensitization: inhibition by anti inflammatory treatment. AB - Epidemiological studies have shown a relationship between air pollution and allergic airway disease. In a previous study we have found that exposure to SO2 enhances allergic sensitization to inhaled ovalbumin (OA) in the guinea pig. We have now investigated the influence of pre-treatment with anti-inflammatory drugs on SO2-induced enhancement of allergic sensitization in this model. Four groups of 6 guinea pigs each were exposed to 5 ppm SO2 on 5 consecutive days over 8 h per day with intermittent inhalation of OA, while the air-control group was exposed to clean air and OA. During the period of SO2 exposure and sensitization three experimental groups were treated with indomethacin (group I), methylprednisolone (group M) and nebulized nedocromil sodium (group N), while the control group remained untreated. Guinea pigs were investigated for sensitization to OA by specific bronchial provocation tests using body plethysmographic measurement of compressed air (CA) and by measurement of specific antibody response in serum. While in the SO2-exposed control group 5 of 6 animals reacted to specific bronchial provocation testing (CA median 0.15 ml, range 0-0.175 ml), only 1 animal was sensitized in group M (CA 0 ml, 0-0.125, p < 0.05), whereas no bronchial reactions were seen in groups I and N (CA 0 ml, 0-0.05, p < 0.025). Specific IgG antibody titres increased in the control group (median 43 EU-->85 EU), but not in the treatment groups (medians group I 35 EU-->35 EU, group M 30- >35 EU, group N 64-->50 EU).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422267 TI - Mast-cell-derived mediators induce epidermal cell proliferation: clue for lichenified skin lesion formation in atopic dermatitis. AB - Mast-cell-derived mediators showed mitogenic activities on mouse-transformed epidermal cell line Pam 212 cells. These activities were eluted into the low molecular-weight fractions below a molecular weight of 10 kD on a high performance liquid chromatography TSK 2000G column, and were partially abrogated by antihistamines or anticytokine antibodies, including anti-IL1 alpha, -IL1 beta or IL6 antibodies. Pretreatment of mast cell lines with sodium butyrate enhanced the production of these factors. Calcium ionophore or Concanavalin A (ConA) stimulated mast cells to generate factor production. These results suggest that mast-cell-derived mediators might play some role in epidermal hyperplasia seen in lichenified lesions in atopic dermatitis. PMID- 1422268 TI - Heparin-containing mast cells in the jejunal mucosa of normal and parasitized Mongolian gerbils, Meriones unguiculatus. AB - Histochemical stainability of mast cells in the small intestine of Mongolian gerbils, Meriones unguiculatus, was examined before and after infection with Nippostrongylus brasiliensis, a well-known intestinal helminth inducing intestinal mastocytosis in rats and mice. Mast cells seen in the small intestine of Mongolian gerbils were exclusively formalin-resistant and were strongly stained by berberine sulfate, regardless of whether the animals were normal or infected with N. brasiliensis. Furthermore, they were, either normal or induced by infection, only seen in the lamina propria and submucosa but never seen in the jejunal epithelium. Such histochemical properties and distribution of intestinal mast cells of Mongolian gerbils were different from previously known characteristics of mast cells in the small intestine of rats and other animal species. PMID- 1422269 TI - [Quantitative and qualitative anomalies of sperm in African individuals infected with HIV]. AB - Semen from 16 HIV1-infected african individuals (12 at stage II/CDC; 4 with pre AIDS) has been analyzed both quantitatively (volume; number of spermatozoa) and qualitatively (motility). 12 healthy HIV1-seronegative individuals were recruited as controls. The HIV1-infected patients showed generally abnormalities of the semen: oligospermia (7 cases), azoospermia (3 cases), or asthenospermia (10 cases). These abnormalities were more marked in patients at advanced stages of the HIV infection. In comparison with the control group, the HIV1-infected individuals had more frequently a past history of sexually transmitted diseases. These abnormalities in the composition of the semen in HIV1-infected african individuals could affect the fertility of these men; that could indirectly restrict the risk of congenitally HIV contaminated child. PMID- 1422270 TI - [Cutaneous ulcer from Mycobacterium ulcerans. Apropos of 1 case in French Guiana]. AB - Skin ulcer due to Mycobacterium ulcerans is presented. The patient come from East of French Guyana. Growth of this mycobacteria is obtained with diphasic Lowenstein medium at 30 degrees C. Diagnostic of M. ulcerans results from mycolic acids study. PMID- 1422271 TI - [Where is the diagnosis of anthrax?]. AB - The large use of antibiotics entailed a dizzy fall of the bacteriological positivity in diagnosis of acute anthrax, from 98-100% to 25% in average. Common serological methods are of low sensitivity and not so confluent. The more sophisticated methods (ELISA, EITB) are of a much better sensitivity but their employment in field epidemiological investigations is difficult and does not be suitable for a retrospective diagnosis. These inconveniences can be successfully surmounted by use of the anthraxin skin test. This test allows to diagnose acute anthrax in 98-100% of cases, and retrospectively (from 45 days to 30 years after recovery) in an average of 86.2% of cases. This skin test is simple for use, and does not requires a special medical competence. PMID- 1422272 TI - [Stability and chemosensitivity of Plasmodium falciparum to chloroquine in 1990 and 1991 in Ankazobe, a village in high plateau Madagascar]. AB - The in vivo and in vitro response of Plasmodium falciparum to chloroquine was conducted in Ankazobe, a village located in the high plateau area. These studies confirmed the low level of chloroquine-resistance. The in vivo data indicate the absence of increase resistance during the 2 years study. Chloroquine is still the drug of choice for the treatment of malaria attack in this area. PMID- 1422273 TI - [Rapid diagnosis of malaria. The microwave furnace]. AB - Thick blood is a well known method for malaria diagnosis, very faithful and sensitive, but it could not be used in emergency because it had to dry for many hours. Micro-wave over allows a quick drying (two minutes). Do it can now be used in emergency. PMID- 1422274 TI - [Acanthamoeba keratitis. Morphologic and isoenzymatic study of a strain isolated from a medically treated case]. AB - We report here the third case of Acanthamoeba keratitis discovered in France in a 30 year-old man wearing soft contact lenses. Amoebas of Acanthamoeba genus could be isolated twice from his corneal ulcer with simple ocular swabs. Owing to medical treatment alone, a successful healing of his eye was obtained. The isolated strain was studied morphologically and biochemically: the cysts observed microscopically after silver stain possessed less than six arms surrounded by a non reticulated ectocyst and belonged to group II defined by Pussard and Pons. But the isoenzymatic study of the ocular strain by isofocusing did not allow us to identify it with any one of the 18 reference strains used, although these represent 14 different described species. PMID- 1422275 TI - [Complement to the epidemiologic study of the focus of Schistosoma mansoni bilharziasis in Kara (northern Togo)]. AB - The present study on the focus of schistosomiasis mansoni of Kara (Northern Togo) complements a report already published in the Bulletin de la Societe de Pathologie Exotique in 1988 (9). The following results were obtained through different experiments carried out with snails collected in Kara. According to the season, 3 to 15% of the Biomphalaria pfeifferi studied, were infected. The maximal release of cercariae was observed between 11 am and 1 pm. The survival of cercariae and their ability to infect mice were not superior to 16 hours. Data obtained with the chaetotaxy of miracidia of the Kara strain were compatible with those obtained with african strains by other authors. Moreover, B. pfeifferi from Kara was more susceptible to the Kara strain of Schistosoma mansoni than B. pfeifferi collected in the south of Togo or than B. glabrata from the new world. On the contrary, B. pfeifferi from Kara was susceptible to a strain of S. mansoni from Brazil and was able to produce infectious cercariae. In addition, the search for an animal reservoir was carried out; 3 of the 112 (2.7%) wild rodents captured around the river Kara, were infected. This relatively low number of infected rodents was compatible with the usual findings in Africa where the animal reservoir is considered from human origin and has no importance in the transmission of S. mansoni as it could have in South America and West Indies. PMID- 1422276 TI - [Measure and analysis of urinary bilharziasis incidence levels in the village of Douloumi (Cameroon)]. AB - A study on urinary schistosomiasis was carried out in the village of Douloumi to evaluate the changes in transmission over a one year period. It showed a stable prevalence rate between 1987 and 1988. However close scrutiny of the different population groups showed this apparent stability was the result of several trends: 1) a high incidence among the resident cohort with increase of prevalence among the younger age groups; 2) a high prevalence among individuals emigrating and 3) a low prevalence among immigrants. Incidence is considered as a better tool to evaluate the recent transmission of schistosomiasis, however incidence evaluation depends on the sensitivity of the case ascertainment method. In this study, a comparison of prevalences among a resident cohort was a good substitute to incidence. PMID- 1422277 TI - [Alveolar echinococcosis in China: current data]. AB - Very few information about alveolar echinococcosis in China is available outside the country. The aim of the authors is to give some precisions about the human cases and the infection in the natural animal hosts. It occurs in 3 distinct foci which comprise poor and remote rural areas. Approximately, 420 cases of human disease have been detected, and the most intense focus is Ningxia province in central China. In all areas, the adult tapeworm is frequently found in V. vulpes, V. corsac, and in the domestic dog. The intermediate hosts differ from an area to the others. Their infection rate is high in the central and the northern foci. More researches are needed for improving our knowledge about the epidemiology of the disease. But the actual major requirement is to apply control measures as health education and medical information. PMID- 1422278 TI - [Ivermectin and pregnancy in mass treatment in Mali]. AB - During july 1989, we have done a retrospective study, in Koba's valley in a savanna onchocerciasis area of Mali, after a mass treatment in rural community with ivermectin. 435 women aged from 15 to 45 years, among 461 with can be submitted to ivermectin risk during their pregnancy period, was seen and overhauled. In 1987, the frequency of women who received ivermectin during their pregnancy period (treated by error), was 17.7%, and 17.3% in 1988. We have seen any difference, between exposed and not exposed women to this error ivermectin treatment, comparing their in utero-mortality, new born mortality an the level of malformations. In spite of careful clinical monitoring in the field, the risk to give ivermectin to pregnancy women in rural community, is very high during mass treatment. Because traditionally (taboos), pregnancy is a forbidden subject. Sociological and anthropological studies, pregnancy field laboratory test and health education, are needed in african rural community before mass treatment with ivermectin. PMID- 1422279 TI - [Therapeutic attitudes and malaria in Sanaga Basin (Cameroon)]. AB - In order to evaluate malaria problems such as they are perceived by Sanaga Basin populations in Cameroon, authors appealed to a cluster sample survey on a population sample obtained from a 2 degree population poll in four representative sites. Malaria so defined represents the outstanding endemia by which the most usual therapeutic recourse makes self-medication interfere particularly by amino 4-quinolines. It is convenient to verify the quality of treatment so administered to adapt possibly training objectives of the interested population. In the present context of the chemoresistance extension of plasmodial strains to usual antimalarials, setting up a surveillance system of efficiency is necessary. PMID- 1422280 TI - [The supernatural, health and community action in Black Africa]. AB - Based on the experience of community participation for tsetse control in the Congo, the author attempts to enlarge the reflexion on general health problems in Black Africa. He desires to draw the attention of the readers unfamiliar with anthropology, 1) to the current existence and social importance in the African communities of a particular approach, grounded on belief in the supernatural, radically different from Western thinking, 2) the intrinsic ambiguousness and richness of these ways of thinking, 3) to its great influence in community participation in sanitation programs. The ethical problems involved in the intervention of mediators using traditional or confessional ways of thinking are raised and included in a psychosocial problematic. PMID- 1422281 TI - Iron disorders can mimic anything, so always test for them. AB - Routinely measuring iron status is necessary because not only are about 6% of Americans in significant negative iron balance, but about 1% have iron overload. Serum ferritin is in equilibrium with body iron stores, and is the only blood test that measures them. Barring inflammation, each one ng (0.0179 pmol) ferritin/ml of serum indicates approximately 10 mg (0.179 mmol) of body iron stores. Very early Stage I positive balance is best recognized by measuring saturation of iron binding capacity. Conversely, serum ferritin best recognizes early (Stage I and II) negative balance. Deviations from normal are: 1. Both stages of iron depletion (i.e. low stores, no dysfunction). Negative iron balance Stage I is reduced iron absorption producing moderately depleted iron stores. Stage II is severely depleted stores, without dysfunction. These stages include over half of all cases of negative iron balance. Treated with iron, they never progress to dysfunction, i.e. to disease. 2. Both stages of iron deficiency. Deficiency is inadequate iron for normal function, i.e. dysfunction, disease. Negative balance Stage III is dysfunction without anemia; Stage IV is with anemia. 3. Positive iron balance: Stage I is a multi-year period without dysfunction. Supplements of iron and/or vitamin C promote progression to dysfunction (disease). Iron removal prevents progression. Stage II is iron overload disease, encompassing years of insidiously progressive damage to tissues and organs from iron overload. Iron removal arrests progression. PMID- 1422282 TI - Detection and measurement of cytokines. AB - Accurate and sensitive methods for the measurement and detection of cytokines are an obvious pre-requisite for the study of cytokine biology, biochemistry and the possible involvement of these molecules in pathology. In this review, the various methods available for cytokine measurement and detection (bioassays, immunoassays and other procedures) are described and compared. A critical appraisal of the potential advantages and limitations of the techniques is included. PMID- 1422283 TI - Autocrine growth factors and leukaemic haemopoiesis. AB - Studies on the structure of haemopoiesis in acute myeloblastic leukaemia (AML) has shown the presence of a small population of malignant cells with extensive proliferative and self-renewal properties which are features of stem cells. The requirements of these cells for proliferation have been studied both in clonogenic assays in semi-solid media and in liquid suspension culture. These have demonstrated that AML clonogenic cells from the majority of patients, can be stimulated to proliferate by colony-stimulating factors (GM-CSF, G-CSF and IL-3) as well as other cytokines including interleukin-1 and interleukin-6, all of which are known to stimulate normal haemopoietic progenitors. Unlike normal haemopoietic cells, leukaemic blasts from many patients with AML express transcripts for haemopoietic growth factors including GM-CSF, G-CSF and IL-1 but not IL-3, and secrete growth factor protein. When leukaemic cells are cultured at sufficiently high density to permit cell-cell interactions, autonomous growth of clonogenic cells can be seen. Autonomous growth is related to the autocrine secretion of haemopoietic growth factors including GM-CSF, G-CSF and IL-6. The degree of autonomous colony growth is variable but approximately 70% of AML samples exhibit either partial or totally autonomous growth; the remaining cells being absolutely dependent on exogenous CSF or fail to grow in the culture systems employed. Similar patterns of growth have been found in murine haemopoietic cells lines which have been transformed as the result of the retroviral insertion of genes for GM-CSF or IL-3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422284 TI - Monoclonal antibody (MoAb) therapy in non-Hodgkin's lymphomas. AB - The advance of monoclonal antibody (MoAb) technology in recent years provides a further treatment modality for cancer therapy. In this review, we discussed the various strategies available for MoAb therapy. We also addressed the problems encountered so far in early clinical trials and suggested possible solutions. We finally reviewed some of the interesting clinical studies conducted so far on the use of MoAbs in patients with non-Hodgkin's lymphomas. PMID- 1422285 TI - Mechanisms of action of, and modes of resistance to, alkylating agents used in the treatment of haematological malignancies. AB - Although the alkylating agents were amongst the first non-hormonal compounds to be shown to be active against malignant cells they still rank as some of the most valuable cytotoxic drugs available for the treatment of patients with leukaemia and lymphoma. Melphalan, chlorambucil, busulfan, cyclophosphamide, ifosfamide and the nitrosoureas are all members of this class of drug, which are believed to exert their cytotoxic effects through the covalent linkage of alkyl groups to DNA. In the first report describing the use of alkylating agents in clinical practice the problem of drug resistance was recognised. In spite of this there is still comparatively little known about the mechanisms underlying the development of resistance as it occurs in patients. Studies using animal models and cell lines have suggested that both cellular and extracellular factors may be involved, but the precise relevance of these to the clinical setting is unclear. A greater understanding of the mode of action and mechanisms of resistance to alkylating agents should enable the development of modulators capable of the restoration of sensitivity to resistant cells, and the more effective use of these well established drugs. PMID- 1422286 TI - The practical management of haemophilia. AB - Haemophilia is a rare and complex disorder and its successful management will depend upon the establishment of a network of 'comprehensive care' including the services of haematologists, orthopaedic surgeons, rheumatologists, dental surgeons, physiotherapists, specialised nurses and counsellors. One of the major lessons to be learned from the HIV epidemic in haemophilia is that it is critical to strive to obtain the safest and purest forms of blood products for these patients. The advent of clinically available recombinant factor VIII is expected soon; in the meantime there is a move towards treating all patients with high purity products. PMID- 1422287 TI - Transligamentary anesthesia: a review. AB - Intraligamentary anesthesia or, as we prefer to call it, transligamentary anesthesia (TLA) is one of the more recent developments in the field of pain blockage in dentistry. This review article organizes the vast amount of information, both current as well as past, found in the dental literature. After a general historical introduction, indications for TLA use are explained. This is followed by a technical examination of the anesthesia, including the various syringes in use, the preferred injection technique, and the types and volume of anesthesia solutions used. Other aspects of TLA, including the rate of success, onset time, duration, and animal/laboratory studies, are then examined. The various advantages and disadvantages of TLA are discussed along with adverse reactions, limitations, and patient acceptance. The article closes with a look at the diagnostic possibilities of the injection as well as a call for future research on this important development. PMID- 1422288 TI - Effects of epinephrine and norepinephrine contained in 2% lidocaine on hemodynamics of the carotid and cerebral circulation in older and younger adults. AB - The effects of vasoconstrictor-containing local anesthetics on the carotid and cerebral circulation were investigated using an ultrasonic quantitative blood flow measurement system. Nineteen healthy adult volunteers were divided into two groups according to age. The local anesthetics used were 2% lidocaine containing 1:80,000 epinephrine and 2% lidocaine containing 1:25,000 norepinephrine. One (1.8 mL) or two (3.6 mL) cartridges of each anesthetic were injected into unilateral or bilateral maxillary gingivae. Epinephrine-containing lidocaine had little effect on carotid and cerebral hemodynamics. Norepinephrine-containing lidocaine increased arterial blood pressure, decreased heart rate, and decreased carotid arterial blood flow and velocity, which caused increased cerebrovascular resistance and decreased cerebrovascular capacitance. The results suggest that norepinephrine may induce vasoconstriction of the cerebral blood vessels in both young and old adults in a dose-dependent manner. These changes appear to be greater in older people. PMID- 1422289 TI - Anesthesia for temporomandibular arthroplasty in a quadriplegic patient: a case report. AB - A 41-year-old male quadriplegic patient with bilateral TMJ ankylosis was admitted for surgery under general anesthesia. Preoperative tests showed abnormal lung function and a low total serum calcium level. Premedication consisted of diazepam 10 mg orally and glycopyrrolate 0.2 mg intramuscularly 90 minutes before the start of the operation. Because of an inability to open the mouth more than 0.5 cm, a nasal fiberoptic endoscopic intubation was done under sedation and local anesthesia. For maintenance of anesthesia the patient received nitrous oxide 50% in oxygen, halothane, and alfentanil. No muscle relaxant was administered. The 2 hour operation was completed uneventfully and the patient needed no ventilatory support afterward. Major anesthetic problems of spinal injury patients can be compared to those with cervical cord transection. The stage that the condition has reached determines the dominant anesthetic problems. The chronic stage (greater than 3 months postinjury, as in this patient) is usually characterized by sympathetic overactivity. Anesthetic problems during this stage may include risk of hyperkalemia from succinylcholine, cardiovascular instability and autonomic hyperreflexia, impaired thermoregulation, anemia, chronic infections, risk of hypercalcemia, and alveolar hypoventilation. None of these problems was encountered in this patient. A surprising finding was that the low serum calcium concentration did not influence the anesthetic outcome. PMID- 1422290 TI - Experience with triazolam in preschool children. AB - Triazolam (0.125 to 0.25 mg) was administered preoperatively to 17 unmanageable children aged 22 to 65 months. The children were monitored visually and by pulse oximeter. No child experienced any airway obstruction and none had oxygen saturation below 90%. Older children had lower SaO2 values than younger children. There was no relationship between the mg/kg dose and SaO2 values. PMID- 1422292 TI - Emergency treatment in Australia. AB - This short communication describes the key points of the emergency medical treatment situation for dentists in Australia. Dental school training and postgraduate educational opportunities in emergency medicine, emergency equipment and drugs found in a typical dental office, and use of the EMS by dentists are covered. PMID- 1422291 TI - Effects of different lidocaine sprays for topical anesthesia on cardiovascular parameters and oxygen saturation. AB - The effects of three lidocaine-containing solutions with and without frigen (freon-113) as a propellant on cardiovascular parameters and oxygen saturation, after different waiting periods and with different dosages applied, were investigated in 130 outpatients undergoing dental treatment in the maxilla under local anesthesia. They were divided randomly into five groups: (A) Xylocaine spray with frigen, two applications (20 mg lidocaine); (B) Xylestesin spray with frigen, two applications (14 mg lidocaine); (C) Xylestesin spray with frigen, three applications (21 mg lidocaine); (D) Xylestesin pump spray without frigen, two applications (14 mg lidocaine); and (E) no topical anesthesia. They were further divided into 12 subgroups to evaluate the influence of waiting periods between the application of the local anesthetic and the injection (1, 2, or 3 minutes). Without topical anesthesia and after the 1-minute waiting period, cardiovascular parameters increased immediately after the injection; after 2- and 3-minute waiting periods the increases were far less pronounced. The mean oxygen saturations did not change during the observed period. The higher lidocaine dosage administered (21 mg) did not intensify the positive impact on the cardiovascular parameters compared to the lower dosage (14 mg). The new pump spray without frigen proved to be as effective as the traditional, ecologically harmful aerosol sprays. PMID- 1422293 TI - Physical evaluation of the patient. AB - The physical evaluation of the patient before and during anesthesia and sedation is assuming an ever greater importance with the advent of sophisticated and reliable monitoring devices. This paper reviews the possible methods of evaluation and describes the types of mechanical monitors most suited to the dental office. PMID- 1422294 TI - IFDAS Research Council Report 1988-91: Midazolam. PMID- 1422295 TI - Isolation of human tumor cells that produce cementum proteins in culture. AB - We have cultured cells from explants of a human cementum tumor. The cells obtained were multipolar, they formed network-like structures and they were alkaline-phosphatase positive. Immunostaining and Western blots using specific antibodies revealed that these cells produced bone sialoprotein and collagen types I and V, and they also mineralized in vitro. Conditioned medium was mitogenic to fibroblasts and mitogens present were separated by heparin-affinity chromatography. Based on affinity to heparin and antibody-inhibition studies, the heparin fractions were shown to contain cementum-derived growth factor, platelet derived growth factor and fibroblast growth factors. The cementum tumor cells, but not gingival fibroblasts, were stained positively by an antibody to cementum derived attachment protein. The attachment protein was separated by immunoaffinity chromatography, and Western blots revealed that the preparation contained 56-kDa and 43-kDa proteins as major bands. Cells pulse-labeled with radioactive amino acids contained a 43-kDa protein as the major component; however, this protein was absent after a cold chase in the presence of cycloheximide, but 56-kDa, 39-kDa and 26-kDa species became prominent. These data indicated that the 56-kDa cementum attachment protein is derived from a 43-kDa precursor. Our data show that the cells cultured from the cementum tumor represent cementum cells capable of synthesizing and secreting cementum proteins in culture. PMID- 1422296 TI - Chromogranin-A secretion from individual parathyroid cells: effects of 1,25-(OH)2 vitamin D3 and calcium. AB - Chromogranin-A (CgA) is a 50-kDa protein located in and secreted by most endocrine and neuroendocrine cells along with native hormone. In the parathyroid gland, CgA is cosecreted with parathyroid hormone (PTH). Although these peptides are secreted together, recent evidence has suggested that they are processed differently in response to stimuli, such as 1,25-(OH)2 vitamin D3 and calcium. We have validated a reverse hemolytic plaque assay for studying CgA release from parathyroid cells. This assay allows for the detection of quantitative changes in hormone secretion from individual parathyroid cells. Bovine parathyroid cells were mixed with protein-A-linked ovine erythrocytes (oRBC) and plated in a monolayer in the presence of CgA antiserum. After incubation, complement was added to the cells to induce cell lysis. Lysis of oRBC around a parathyroid cell indicated the release of CgA from a cell. Results showed that plaque formation was dependent on assay reagents and that serial dilution of the antibody reduced plaque formation. CgA secretion was inhibited by increasing concentrations of calcium and stimulated by increasing concentrations of 1,25-(OH)2vitamin D3. PMID- 1422297 TI - Effects on cultured neonatal mouse calvaria of 1 alpha,25-dihydroxyvitamin D3, 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 and 26,26,26,27,27,27 hexafluoro-1 alpha,23S,25-trihydroxyvitamin D3. AB - The potency of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 (26,27 F6-1,25(OH)2D3) to enhance bone calcium (Ca) mobilization in vitro was higher than that of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). In a 48-h organ culture system using fetal rat limb bones, effects of 26,27-F6-1,25(OH)2D3 on bone resorption were similar to those of 1,25(OH)2D3. Thus, we attempted to clarify whether or not the potency of 26,27-F6-1,25(OH)2D3 in bone resorption in vitro would be higher than that of 1,25(OH)2D3. Calvarial bones from neonatal mice were used as explants and the culture period was extended to 144 from 48 h. In cultures of 0 to 48 h, both drugs increased the release of prelabeled 45Ca from cultured calvariae, in a dose-dependent manner. In cultures of 48 to 144 h, 26,27-F6-1,25(OH)2D3 was much more effective than 1,25(OH)2D3 regarding indices of bone resorption. 26,26,26,27,27,27-F6-1 alpha,23S,25-trihydroxyvitamin D3 (26,27-F6-1,23,25(OH)3D3), a main metabolite of 26,27-F6-1,25(OH)2D3 in rats, stimulated 45Ca release equipotently to 1,25(OH)2D3. In mouse bone marrow cells cultured for 7 days, the potency of 26,27-F6-1,25(OH)2D3 on osteoclast formation was much higher than 1,25(OH)2D3. These results suggest that the higher potency of 26,27-F6-1,25(OH)2D3 in bone resorption may be due at least in part to both the higher potency of 26,27-F6-1,25(OH)2D3 in osteoclast formation and the larger retention of 26,27-F6-1,23,25(OH)3D3 in calvariae. PMID- 1422298 TI - Preferential osteopenia in women with osteoporotic fractures. AB - One-hundred thirty-six women with spontaneous vertebral crush fractures had bone density measurements by photon absorptiometry. Their absolute and relative extent of osteopenia were expressed as Z scores with respect to values from normal white women. Absolute Z scores were used to express the mean bone mass of women with crush fractures vis-a-vis normal women at peak bone mass; relative Z scores were used to express the same means vis-a-vis age-matched controls. The skeletal sites measured included the distal radius, lumbar spine, and three sites on the femur (neck, Ward's triangle, and trochanter). The absolute deficit for the five sites ranged from -1.66 to -2.60. The relative deficit was close to 1 SD for all sites. A discriminant analysis revealed that the spine and femur were predictive for vertebral crush fractures but the radius was not. Comparison with a previously reported hip-fracture population (n = 31) showed that the low bone density of the spine separated the two fracture groups best. We propose the following: (a) vertebral-fracture patients have extensive generalized osteoporosis including the hip with a preferential deficit in the spine and (b) hip-fracture patients have generalized osteoporosis with preferential osteopenia of the hip and do not have a greater mineral deficit in the spine or radius than age-matched normal women. It may be that if a single site is to be selected for screening for spine and hip fractures, the greatest value would be in measurement of the femur, although ideally the skeletal site of interest would be measured. Prospective studies are needed to confirm the utility of measurements at the spine and hip in prediction of future fractures. PMID- 1422301 TI - Selected bibliography. PMID- 1422299 TI - Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients. AB - We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling. PMID- 1422302 TI - Trans-differentiation of hypertrophic chondrocytes into cells capable of producing a mineralized bone matrix. AB - Trans-differentiation of hypertrophic chondrocytes into bone-forming cells was observed when femurs from 14-day-old chick embryos were cut through the region of hypertrophic cartilage and the separated pieces were cultured for 2-18 days. Inside many chondrocytic lacunae a new matrix was present which had the staining characteristics of bone matrix including birefringence and the capacity to mineralize. The cells within the lacunae had the characteristics of osteoblasts, such as alkaline phosphatase activity and positive immunocytochemical staining for osteocalcin, osteonectin, osteopontin and type I collagen. Chondrocyte necrosis and empty lacunae were only observed immediately at the cut edge, and in that region no bone-forming cells were present inside the lacunae. Where bone matrix was present, the lacunae had remained intact, the cells were viable and no evidence of cell migration was observed. This suggested that the bone-forming cells had originated from the hypertrophic chondrocytes. The temporal sequence of events was followed closely. Two days following the cut only a few chondrocytes showed a positive reaction for osteocalcin, osteonectin, osteopontin and the type I collagen. At that time no such reaction product was observed in the chondrocytes of uncut femurs. Many hypertrophic chondrocytes divided, as shown by tritiated thymidine incorporation. The rate of cell division increased between 2 6 days, when several smaller basophilic cells were present inside the lacuna instead of the single hypertrophic chondrocyte. These cells expressed alkaline phosphatase activity, were positive for fibronectin, the above non-collagenous bone proteins and type I collagen. The bone matrix that was observed after 6-18 days was initially confined to the inside of the chondrocytic lacunae, but later spread beyond the lacunar confines. The bone proteins were still associated with the bone-forming cells, but fibronectin was absent when matrix formation was evident. Mineralization of the intra-lacunar osteoid took place after 12-18 days. It is speculated that the trans-differentiation was initiated by disruptions of the normal cell-cell associations. PMID- 1422300 TI - Comparison of single-photon and dual-energy x-ray absorptiometry of the radius. AB - We compared dual-energy x-ray absorptiometry (DXA) for measurement of the radius with the conventional single-photon absorptiometry (SPA) method. To evaluate reproducibility, 34 healthy male and female subjects were measured twice each by both methods. While the instruments measured bone mineral content (BMC) similarly, projected area was consistently lower by SPA and therefore bone mineral density (BMD) was higher by an average of 10%. We report similar coefficients of variation for the two methods, which are 0.8% (SPA) and 0.7% (DXA) for BMC (P = 0.71) and 0.8% (SPA) and 1.4% (DXA) for BMD (P = 0.02). We also evaluated the relationship between the methods with data from 196 clinic patients who were measured once each on both instruments. The BMD measurements from the two instruments were highly correlated (r = 0.97) in these patients, which permits the conversion of databases from SPA to DXA-equivalents. We conclude that DXA can replace SPA for radial bone densitometry. PMID- 1422303 TI - The anabolic action of 17 beta-estradiol (E2) on rat trabecular bone is suppressed by (3-amino-1-hydroxypropylidene)-1-bisphosphonate (AHPrBP). AB - We have previously found that high doses of 17 beta-estradiol (E2), similar to those seen in late pregnancy, stimulate bone formation in adult rats. In this communication we tested the effects of a combination of E2 and (3-amino-1 hydroxypropylidene)-1,1-bisphosphonate (AHPrBP) on bone formation and bone volume in rat bone. E2 (4 mg/kg/day subcutaneously for 17 days) stimulated the bone formation rate to 6 times that of control rats. This was reduced by a single administration of AHPrBP (0.3 mg/kg subcutaneously) to 3 times control levels, and by similar daily injections of AHPrBP to levels not significantly different from those of untreated rats. Suppression of bone formation was effected predominantly through a reduction in the percentage of double-labelled surfaces, consistent with reduced osteoblast recruitment. We found only relatively minor effects of AHPrBP on the mineral apposition rate, suggesting that AHPrBP affected osteoblast function less than osteoblast recruitment. Suppression of histodynamic parameters of bone formation by AHPrBP was associated with suppression of the increase in bone volume otherwise induced by E2. The suppression by AHPrBP of the effect of E2 on bone formation contrasted with its lack of effect on other target tissues for E2, since AHPrBP did not affect the E2-induced changes in longitudinal bone growth or uterine weight. These results suggest that AHPrBP inhibits the anabolic effect of estrogen on rat trabecular bone. PMID- 1422304 TI - Calcium ion transport kinetics during dentinogenesis: effects of disrupting odontoblast cellular transport systems. AB - Due to strongly discrepant results in the literature, controversy exists about the timing of the transport of Ca2+ ions to the mineralization front during dentinogenesis and the role of the odontoblasts in this transport. The present study gives evidence, by means of autoradiography as well as by a radiochemical technique, that the transport time for Ca2+ ions into the dentin mineral phase is about 10-15 min in the rat incisor. The results also show that technical factors, such as mode of tracer injection and the use of perfusion fixation, may influence the results more or less strongly. Finally, by disturbing odontoblast microtubules, involved in intracellular transport processes, and by blocking odontoblast calcium uptake channels by nifedipine and neomycin, the Ca2+ ion transport into dentin mineral was found to be strongly impaired. This may be taken as an indication that transcellular calcium transport mechanisms have a role during dentinogenesis. PMID- 1422305 TI - Prostaglandin E2 prevents ovariectomy-induced cancellous bone loss in rats. AB - The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent ovariectomy-induced cancellous bone loss. Thirty-five 3-month-old female Sprague-Dawley rats were divided into two groups. The rats in the first group were ovariectomized (OVX) while the others received sham operation (sham-OVX). The OVX group was further divided into three treatment groups. The daily doses for the three groups were 0, 1 and 6 mg PGE2/kg for 90 days. Bone histomorphometric analyses were performed on double-fluorescent-labeled undecalcified proximal tibial metaphysis (PTM). We confirmed that OVX induces massive cancellous bone loss (-80%) and a higher bone turnover (+143%). The new findings from the present study demonstrate that bone loss due to ovarian hormone deficiency can be prevented by a low-dose (1 mg) daily administration of PGE2. Furthermore, a higher-dose (6 mg) daily administration of PGE2 not only prevents bone loss but also adds extra bone to the proximal tibial metaphyses. PGE2 at the 1-mg dose level significantly increased trabecular bone area, trabecular width, trabecular node density, density of node to node, ratio of node to free end, and thus significantly decreased trabecular separation from OVX controls. At this dose level, these same parameters did not differ significantly from sham-OVX controls. However, at the 6-mg dose level PGE2, there were significant increases in trabecular bone area, trabecular width, trabecular node density, density of node to node, and ratio of node to free end, while there was significant decrease in trabecular separation from both OVX and sham-operated controls. The changes in indices of trabecular bone microanatomical structure indicated that PGE2 prevented bone loss as well as the disconnection of existing trabeculae. In summary, PGE2 administration to OVX rats decreased bone turnover and increased bone formation parameters resulting in a positive bone balance that prevented bone loss (in both lower and higher doses) and added extra bone to metaphyses of OVX rats (in higher dose). These findings support the strategy of the use of bone stimulation agents in the prevention of estrogen depletion bone loss (postmenopausal osteoporosis). PMID- 1422306 TI - Differential chemotactic responses of different populations of fetal rat calvaria cells to platelet-derived growth factor and transforming growth factor beta. AB - We tested the chemotactic response to platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF beta) of cells released enzymatically from fetal rat calvaria (RC). Both factors were chemotactic for RC cells, but the magnitude of the chemotactic response differed markedly between different populations and varied with time in culture of the cell populations. Cells released earlier from the calvaria showed a greater response than osteoblast enriched populations released later. The optimal concentration of PDGF was the same for both alkaline phosphatase (AP)-positive and AP-negative cells within the populations. However AP-positive cells showed two peaks of response to TGF beta; one peak coincided with the TGF beta concentration also maximally affecting AP negative cells, while the other occurred at a concentration 50-100 times higher. The results indicate that PDGF and TGF beta are chemotactic for both AP-positive and AP-negative cells in populations of cells derived from fetal calvariae, that chemotactic response declined with longer periods of time in culture, and that AP positive osteoblast-like cells respond to a concentration of TGF beta that does not affect the AP-negative cells in the population. PMID- 1422307 TI - The dose-dependency of alcohol-induced hypoparathyroidism, hypercalciuria, and hypermagnesuria. AB - Ingestion of alcohol evokes hypoparathyroidism, hypercalciuria, and hypermagnesuria. The dose-dependency of these changes has not been assessed before. We measured the serum concentrations of intact parathyroid hormone (PTH), and serum and urine calcium and magnesium in six normal men before and at intervals up to 6 h after the ingestion of fruit juice (control) and 0.5, 1.0 and 1.3 g of alcohol per kg of body weight. As compared with the control experiment the maximum reductions in the mean PTH concentration were 31% (P = 0.19), 31% (P = 0.20) and 45% (P = 0.01) with the three alcohol doses, respectively. After stopping drinking, the urinary excretion of calcium was 85%, 142% and 207% higher during the three alcohol experiments than during the control session (P < 0.05, < 0.01 and < 0.01, respectively), also urinary magnesium increased up to threefold. We conclude that in nonalcoholic subjects acute alcohol intake induces hypoparathyroidism, hypercalciuria, and hypermagnesuria, the latter two being dose-dependent. The direct renal effects of alcohol are the major mechanisms for hypercalciuria and hypermagnesuria, but hypoparathyroidism contributes to hypercalciuria at high levels of alcohol intoxication. PMID- 1422308 TI - Bone mineral density during puberty in western Canadian children. AB - To assess the influence of puberty and its associated changes in body weight and height on bone mineral density (BMD), lumbar spine (L2-L4) and femoral neck BMD were measured in 74 healthy, active children (9-16 years) using dual-photon absorptiometry. Competitive swimmers were recruited to minimize the potential effect variability in mechanical loading regime may have on bone density of the lumbar spine. Tanner staging was used to assess stage of puberty. Current dietary calcium intake was assessed by analysis of 6-day dietary records. Significant differences in spinal and femoral neck BMD occurred between early (Tanner 1 and 2) and late stages of puberty (Tanner 4 and 5), P < 0.05. A significant correlation was found between bone density and dietary calcium intake. However stepwise regression analyses demonstrated stage of puberty or body weight were the only factors which significantly affected spinal BMD, accounting for 77% and 68% of the variability respectively; while at the femoral neck, body weight accounted for 52% of the variability. These results demonstrate that when potential interacting factors are controlled for through regression analyses, differences in BMD occur mainly as a function of puberty and the associated gains in body weight. PMID- 1422309 TI - Acronyms in bone densitometry. PMID- 1422310 TI - Hormone responses of in vitro bone nodule cells: studies on changes of intracellular calcium and membrane potential in response to parathyroid hormone and calcitonin. AB - We used two techniques to study the responses of individual in vitro bone nodule cells to parathyroid hormone (PTH) and calcitonin (CT). These techniques are laser scanning confocal imaging with a fluorescent indicator to measure intracellular free [Ca2+], and microelectrode impalement to measure the electrical potential difference across the cell membrane. We applied these measurement techniques to cells in the top cellular layer of nodules that form in vitro in cultures of cells obtained from fetal rat calvaria. Our measurements showed a transient increase in intracellular free [Ca2+] following application of PTH or CT. The duration of the increase in fluorescent intensity following PTH application varied from about 100 to more than 300 s, and the duration following CT application was from 30 to 80 s. In some measurements we applied both hormones in sequence, and observed that some cells showed an intracellular [Ca2+] response to both hormones, while other cells apparently responded to only one or the other of the hormones, or to neither. We also observed membrane potential changes in response to PTH and to CT. The membrane potential response to CT was quite small. The time courses of these membrane potential changes consisted of a depolarizing phase lasting about 100 s (with both hormones) followed by a hyperpolarizing phase (with PTH). Control measurements using only the vehicle solutions were carried out with both techniques, producing negligible responses. PMID- 1422311 TI - The effect of rat parathyroid hormone (1-34) infusion on urinary 3 hydroxypyridinium cross-link excretion in the rat. AB - The utility of measurement of the urinary excretion of the 3-hydroxypyridinium cross-links, pyridinoline (Pyr) and deoxypyridinoline (Dpyr) as indices of bone resorption in rats was investigated. Total Pyr and Dpyr excretion were measured in young rats treated by s.c. infusion with rat parathyroid hormone (1-34) (PTH) at 22-30 micrograms/kg/day or with diluent (controls) for 14 days. During infusion, average urinary excretion of both cross-links was significantly higher in PTH rats (Pyr: 11.77 +/- 0.44 nmol/day), Dpyr: 15.81 +/- 0.95 nmol/day) than in controls (Pyr: 10.17 +/- 0.35 nmol/day, Dpyr: 12.03 +/- 0.67 nmol/day). These results were consistent with the magnitude of the expected increase in bone resorption rate with this dose of PTH. The method appears to provide a sensitive measure of bone resorption for in vivo bone studies in rats. PMID- 1422312 TI - Decreased heterotopic osteogenesis in vitamin-D-deficient, but normocalcemic guinea pigs. AB - The effect of vitamin D deficiency unhampered by hypocalcemia on de novo bone formation was studied in guinea pigs. Heterotopic induction of osteogenesis was evaluated 4 weeks after intramuscular transplantation of allogenic urinary bladder transitional epithelium from vitamin-D-repleted (+D) donors into +D and D recipients. In -D recipients the frequency of osteogenesis and the amount of induced bone were significantly diminished; induced bone was less mature, scantly cellular woven bone poorly repopulated with bone marrow. No effect of vitamin D deficiency on orthotopic bone growth and on mineralization of orthotopic and heterotopically induced bone was observed. It is proposed that in addition to inducing factors (BMPs, growth factors) which may be responsible for transformation of mesenchymal cells to osteoprogenitor cells, normal concentrations of 1,25-(OH)2D3 may be required for proliferation and further differentiation of these cells into osteoblasts and for expression of genes engaged in extracellular matrix formation and maturation. PMID- 1422313 TI - Familial idiopathic hyperphosphatasia (FIH): response to long-term treatment with pamidronate (APD). AB - A 5-year-old child suffering from familial idiopathic hyperphosphatasia (FIH) was treated by: (1) intravenous infusion of pamidronate (APD) (3 h) (0.75 mg/kg/day) for 5 days; and (2) oral administration of APD (8 mg/kg/day) for 1 year, in association with calcium (1 g/day) as calcium gluconate. A decrease of both serum calcium and phosphate, and a slight PTH increase were observed immediately after the IV treatment; serum alkaline phosphatase did not change, but a marked and rapid decline in the hydroxyprolinuria was observed: basal 659 +/- 207 during IV treatment 169 +/- 59 (mean +/- SD mg/24 h, P < 0.005). At the end of one year of oral APD treatment clinical and radiological findings showed a remarkable improvement. Serum calcium, phosphate and PTH returned to the initial values. Plasma alkaline phosphatase levels showed a 70% decrease: basal 1370 IU/l, 1 year 410 IU/l whereas the hydroxyprolinuria values were similar to those determined at the end of the intravenous treatment (212 +/- 13 mg/24 h), but still significantly lower than the basal levels (P < 0.01). No side-effects were observed. APD appears to be a promising treatment for patients with FIH. PMID- 1422314 TI - Osteoporosis and calcification of the aorta. AB - In an age-stratified random sample of 200 Rochester, Minnesota women, the prevalence of aortic calcification rose with aging, as did the prevalence of vertebral fractures, while bone mass fell. The statistically significant positive association of aortic calcification with vertebral fractures and the negative associations with bone mass at six skeletal sites were mainly accounted for by age. After age-adjustment, the only association remaining was a negative one between calcified aortic plaques and bone mineral density (BMD) of the lumbar spine (P < 0.05). Aortic calcification was not associated with any measures of calcium metabolism, after adjusting for age, except for a slight negative association between linear aortic calcifications and 25(OH) vitamin D levels (P < 0.05). BMD values of the lumbar spine were somewhat greater than predicted for age in women with severe aortic calcification, but similar findings were seen at other skeletal sites and none of the differences was statistically significant. While overestimation of bone mass was generally minimal, severe aortic calcification may distort lumbar spine assessments in a minority of postmenopausal women. PMID- 1422315 TI - Selected bibliography. PMID- 1422316 TI - Cytological and ultrastructural investigation on osteoblastic and preosteoclastic cells grown in vitro in the presence of ipriflavone: preliminary results. AB - The effects of ipriflavone on bone cells were studied in vitro on pre osteoclastic (FLG 29.1) and osteoblast-like (Saos-2) cells grown for 48 h either separately or in co-cultures, with or without the addition of PTH. Histological, ultrastructural and histochemical (TRAP-activity demonstration) methods were used. The main results show that ipriflavone reduces replication of FLG 29.1 cells and inhibits TRAP production by these cells both in controls and in co cultures treated with PTH. Moreover, it has a moderate stimulatory effect on proliferation of osteoblast-like cells and reduces the PTH-induced degenerative changes of Saos-2 cells. These results suggest that the inhibitory effect of ipriflavone on FLG 29.1 cells might be indirect and might be mediated by the osteoblast-like cells. PMID- 1422317 TI - Effects of ipriflavone on bone remodeling in primary hyperparathyroidism. AB - The aim of this study was to evaluate the effects of ipriflavone treatment on bone remodeling in primary hyperparathyroidism. Nine patients, 6 females and 3 males (mean +/- SD age 56 +/- 12.5 years) were treated with 1200 mg/day of ipriflavone by oral administration divided in 3 daily doses. All patients were treated for 21 days; in 5 patients treatment was prolonged to 42 days. In all patients the main serum and urinary parameters of bone remodeling were evaluated. The results suggest that ipriflavone affects bone remodeling by inhibiting bone resorption without affecting bone formation. Ipriflavone is, therefore, indicated in the treatment of metabolic bone diseases characterized by a high bone turnover. PMID- 1422318 TI - Flavonoids: biochemical effects and therapeutic applications. PMID- 1422319 TI - Short-term treatment of Paget's disease of bone with ipriflavone. AB - Ipriflavone (IP), an isoflavone derivative, seems to prevent the loss of bone mass through the inhibition of bone resorption, mainly inhibiting the recruitment of osteoclasts. We investigated whether a brief course of treatment with IP can reduce biochemical parameters of accelerated bone turnover and bone pain in patients with active Paget's disease of bone. Sixteen patients (9 males and 7 females) with active Paget's disease were randomly allocated to two different crossed-over dose regimens of treatment with IP (600 mg/day vs. 1200 mg/day). Each treatment course lasted 30 days and the wash-out period between the two sequences was 15 days. Serum alkaline phosphatase (Al.Ph.) and urinary hydroxyproline/creatinine excretion (HOP/Cr) were reduced after each sequence. At the end of the 600/1200 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 32% and 25.6% respectively. At the end of the 1200/600 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 33% (P < 0.01) and 24.1% (P < 0.05) respectively. Furthermore, a significant decrease in bone pain was observed during the 1200/600 mg/day sequence (P < 0.01). Both treatment schedules were well tolerated and the patients' compliance resulted excellent. Our results indicate that short-term treatment with IP can reduce biochemical parameters of disease activity and bone pain in patients with active Paget's disease of bone. PMID- 1422320 TI - Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis. AB - Recently it has been demonstrated that ipriflavone (IP), an isoflavone derivative, is able to increase bone mass in patients with established postmenopausal osteoporosis (PMO). Here we present a preliminary report of a 2 year multicenter, double-blind, placebo-controlled clinical study performed in order to evaluate the efficacy and tolerability of IP in PMO. A large number of patients with PMO, referred to 12 Italian centers, was randomly divided into 2 groups and treated with oral IP (600 mg/day) or placebo (Pl). All patients received an oral Ca supplement (1 g/day). One hundred and twenty six patients completed 1 year of the study. Bone mineral density (BMD) of the distal radius, measured by DPA, serum osteocalcin (BGP), and urinary hydroxyproline excretion (HOP/Cr), were measured before and after 12 months. After 12 months, a significant increase in BMD was observed in the IP-treated group (P < 0.05). IP determined a reduction of HOP/Cr, while in Pl-treated patients a significant increase of this index, as well as of BGP, was observed. After 12 months the difference between the two groups resulted significant (P < 0.05) for BGP. The drug was well tolerated and the patients' compliance to the oral treatment resulted excellent. The results of this study indicate that IP is able to increase bone mass in patients with PMO. PMID- 1422321 TI - Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium. AB - Estrogen replacement therapy can counteract all postmenopausal symptoms. While low estrogen doses (0.15-0.30 mg of conjugated estrogens/day) can counteract neurovegetative and psychological symptoms, higher estrogen doses (at least 0.625 mg of conjugated estrogens/day) are required to prevent bone mineral loss in postmenopausal women. However, if contra-indications to high estrogen doses exist, drugs other than estrogens can represent a suitable treatment for postmenopausal osteoporosis both alone or in combination with low estrogen doses. Experimental and clinical data have shown that ipriflavone is effective in the treatment of established postmenopausal osteoporosis. With the purpose of evaluating whether ipriflavone is able to enhance estrogen activity on bone metabolism, 133 postmenopausal women were randomly submitted to the treatment with: (1) placebo; (2) 0.15 mg/day of conjugated estrogens; (3) 0.30 mg/day of conjugated estrogens; (4) 0.15 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone; (5) 0.30 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone. One g/day of calcium supplementation was given to all women. In all subjects bone mineral density was measured before and after 6 and 12 months of treatment at the distal radius by dual-photon absorptiometry. A moderate decrease of bone mineral density was evidenced in women submitted to placebo or to estrogen therapy alone. By contrast, an increase of BMD was measured after 12 months of treatment in the women treated with 0.15 (not significant) or 0.30 mg/day (P < 0.01) of conjugated estrogens associated with ipriflavone. Both dosages of conjugated estrogens were able to induce a significant reduction of neurovegetative symptoms. The increase of bone density obtained with the combination of conjugated estrogens with ipriflavone demonstrates that this combination improves the effects of low estrogen doses on bone mass representing a satisfactory approach in the prevention and treatment of all symptoms related to the climacteric syndrome. PMID- 1422322 TI - Effect of ipriflavone on bone mass in elderly osteoporotic women. AB - A study in elderly osteoporotic women was performed to assess the effect of one year treatment with ipriflavone (IP) on bone mass and bone biomarkers. Twenty eight women aged over 65, with diagnosis of osteoporosis and X-ray evidence of at least one vertebral fracture, were treated with IP tablets (600 mg/day) or placebo (PL), according to a randomized, double-blind, parallel-group design. One g/day calcium supplementation was given to all patients. After 12 months a significant increase (+6%, P < 0.05) of bone mineral density (BMD) at the distal radius (DPA) was obtained in the IP-group. Serum osteocalcin (BGP) and urinary HO proline/creatinine (HOP/Cr) values were reduced in the same group. BMD values did not change (-0.3%) in the placebo group. One woman of the PL-group was withdrawn from treatment because of worsening of pain, due to new vertebral crushes. Side effects (mainly gastrointestinal) arose in 8 IP- and in 5 PL-treated women. The compliance to the oral administration was good. PMID- 1422323 TI - Rabies in Europe. PMID- 1422324 TI - On site medical services at major incidents. PMID- 1422325 TI - Radioiodine for hyperthyroidism. PMID- 1422326 TI - Euthanasia: time for a royal commission. PMID- 1422328 TI - Severity of imported falciparum malaria: effect of taking antimalarial prophylaxis. AB - OBJECTIVE: To investigate the effects of antimalarial chemoprophylaxis and other variables on the severity of falciparum malaria. DESIGN: Review of consecutive malaria cases between 1987 and 1991. SETTING: The Hospital for Tropical Diseases, London. SUBJECTS: 250 consecutive cases of mild and 51 consecutive cases of severe falciparum malaria. RESULTS: Prophylaxis was taken in 52.4% (131/250) of the cases of mild malaria and 21.6% (11/51) of cases of severe malaria. Severe malaria was more common in white patients than in those of African origin and was also seen more commonly in people returning from central, southern, and east Africa than in those returning from west Africa. Patients with severe malaria presented sooner than patients with mild malaria. CONCLUSIONS: Prior chemoprophylaxis led to a reduction in the severity of falciparum malaria. Ethnic origin, time to presentation, and sex were also associated with the severity of malaria. PMID- 1422327 TI - Preliminary analysis of the care of injured patients in 33 British hospitals: first report of the United Kingdom major trauma outcome study. AB - OBJECTIVE: To measure the effectiveness of management of major trauma in the United Kingdom. DESIGN: Review of the care of all seriously injured patients seen over two years. SETTING: 33 hospitals which receive patients who have sustained major trauma. SUBJECTS: 14,648 injured patients admitted for more than three days, transferred or admitted into an intensive care bed, or dying from their injuries. MAIN OUTCOME MEASURE: Death or survival in hospital within three months of the injury. RESULTS: 21% of seriously injured patients (1299) took longer than one hour to reach hospital. Time before arrival at hospital was not related to severity of injury. A senior house officer was in charge of initial hospital resuscitation in 57% (826/1445) of patients with an injury severity score > or = 16. More senior staff were commonly responsible for definitive operations, but only 46% (165/355) of patients judged to require early operation arrived in theatre within two hours. Mortality for 6111 patients sustaining blunt trauma and treated in the 14 busiest hospitals was significantly higher (actual 408, predicted 295.6, p < 0.001) than in a comparable North American dataset. Large differences in the 14 hospitals assessed could not be explained by variations in case load or facilities. In contrast, the outcome of the 4.1% (597) of patients with penetrating injuries was better than that of a comparable group in the United States. Analysis of the 415 penetrating injuries with complete data showed that 15 patients died (19.3 predicted; p = 0.04). CONCLUSIONS: The initial management of major trauma in the United Kingdom remains unsatisfactory. There are delays in providing experienced staff and timely operations. Mortality varies inexplicably between hospitals and, for blunt trauma, is generally higher than in the United States. PMID- 1422329 TI - Cost of urology: financial audit in a clinical department. AB - OBJECTIVES: To cost a clinical unit over one month in 1991, to cost treatment of individual patients from audit data, and to compare this costing method with the hospital charging system. DESIGN: A financial breakdown was obtained for one month's work. Ward stay, operating time, investigations, and outpatient visits were costed and a formula (episode = days on ward+hours of operating+investigations+outpatient visits) was used to cost patient episodes from audit data. SETTING: The adult urology unit in a teaching hospital. MAIN OUTCOME MEASURES: Costs for each part of patients' treatment. RESULTS: Total cost was 147,796 pounds for 159 admissions, 738 inpatient days, 131 operations in 29 operating lists, and 615 outpatient visits. An uncomplicated transurethral prostatectomy cost 1140 pounds but complications increased this to 1500 pounds in another patient. The costs of diagnostic cystoscopy were 130 pounds in outpatients, 240 pounds in day surgery, and 430 pounds in inpatients. Hospital charges do not reflect the individual costs of treatment, charges being greater than costs for some patients and lower than costs for others. CONCLUSIONS: Clinicians can produce a financial analysis of their work and cost their patients' treatment. Audit is strongly advocated as a resource planning tool. PMID- 1422331 TI - Arrangements for on scene medical care at major incidents. PMID- 1422330 TI - Outcome of breech delivery at term. AB - OBJECTIVE: To compare neonatal mortality and morbidity in term infants presenting by the breech and delivered vaginally or by caesarean section. DESIGN: Population based comparison of outcomes. Data derived from the St Mary's maternity information system. SETTING: North West Thames Regional Health Authority, 1988 90. SUBJECTS: 3447 singleton fetuses presenting by the breech at term. MAIN OUTCOME MEASURES: Intrapartum and neonatal mortality, low Apgar scores, intubation at birth, and admission to special care baby units. RESULTS: After the exclusion of babies with congenital anomalies the incidence of intrapartum and neonatal death associated with vaginal birth was 8/961 (0.83%) compared with 1/2486 (0.03%) in babies born by caesarean section (relative risk 20, 95% confidence interval 2.5 to 163). The numbers of low Apgar scores and neonatal intubation were doubled in babies born vaginally or by emergency caesarean section compared with those delivered by elective operation. CONCLUSIONS: The good neonatal outcome associated with elective caesarean delivery of the term breech fetus may influence the decision of women and their obstetricians about mode of delivery. PMID- 1422332 TI - Conversation with New York's health commissioner. Interview by Fred B. Charatan. PMID- 1422333 TI - Pyruvate kinase deficiency. Association with G6PD deficiency. PMID- 1422334 TI - Psychosis with disulfiram prescribed under probation order. PMID- 1422335 TI - ABC of colorectal diseases. Colorectal disorders in elderly people. PMID- 1422336 TI - Antenatal screening for Down's syndrome. PMID- 1422337 TI - Antenatal screening for Down's syndrome. PMID- 1422338 TI - Antenatal screening for Down's syndrome. PMID- 1422339 TI - Antenatal screening for Down's syndrome. PMID- 1422340 TI - Antenatal screening for Down's syndrome. PMID- 1422341 TI - Antenatal screening for Down's syndrome. PMID- 1422342 TI - Antenatal screening for Down's syndrome. PMID- 1422343 TI - Antenatal screening for Down's syndrome. PMID- 1422344 TI - Antenatal screening for Down's syndrome. PMID- 1422346 TI - Heterosexual AIDs epidemic. PMID- 1422345 TI - Assisted conception on NHS. PMID- 1422347 TI - Low serum cholesterol and violent death. PMID- 1422348 TI - Low serum cholesterol and violent death. PMID- 1422349 TI - Site of injection for vaccination. PMID- 1422350 TI - Early treatment of meningococcal disease. PMID- 1422351 TI - Early treatment of meningococcal disease. PMID- 1422352 TI - Removal of central venous catheter and venous air embolism. PMID- 1422353 TI - Guidance on guidelines. PMID- 1422354 TI - Getting to grips with Archie Cochrane's agenda. PMID- 1422356 TI - Towards a separate adolescent medicine. PMID- 1422355 TI - Breast feeding and HIV infection. PMID- 1422357 TI - Delayed puberty. PMID- 1422358 TI - Can secular trends in child growth be estimated from a single cross sectional survey? AB - OBJECTIVE: To formulate and evaluate a new method to measure secular trends in child growth based on the cross sectional collection of heights of children and young adults. DESIGN: Trends in child growth obtained from comparison of two national surveys made with an interval of 15 years were compared with estimates obtained from comparison of height deficits of children and young adults in the more recent survey. SETTING: Brazil. SUBJECTS: Random sample of children (6 and 7 years old) and young adults (21 and 22 years old) living in Brazil in 1974 and 1989 (a total of 23,271 subjects in 1974 and 5479 in 1989). MAIN OUTCOME MEASURES: Increments in average heights of 6 and 7 year old children in a 15 year period. RESULTS: Mean height of 6 year old children increased 4.0 cm (boys) and 3.3 cm (girls) from 1974 to 1989. Similar results were obtained by subtracting, in the 1989 survey, mean height deficits found at ages 21 and 6 (3.8 cm for males and 3.5 cm for females). Positive changes in the mean height of 7 year old children could also be predicted by subtracting, in the 1989 survey, height deficits found at ages 7 and 22. CONCLUSIONS: Findings of this study support the hypothesis that secular trends in child growth can be estimated by comparing height deficits observed in children and young adults. PMID- 1422359 TI - Effect of maintenance chemotherapy in childhood on numbers of melanocytic naevi. AB - OBJECTIVE: (a) To determine whether children given chemotherapy for haematological malignancy have significantly more melanocytic naevi than age matched children in the local population; (b) to establish whether any observed variation in naevus counts from normal is seen at the start of maintenance chemotherapy. DESIGN: Follow up of 29 consecutive children starting maintenance chemotherapy, with parental interview and count of all melanocytic naevi > or = 2 mm on the child's skin. Assessment repeated three years later after completion of maintenance chemotherapy. Other dermatological problems identified at either visit were also recorded. SETTING: Royal Hospital for Sick Children, Glasgow. RESULTS: At the start of maintenance chemotherapy all children had total body counts of melanocytic naevi within the normal range established for age matched children in the local population. Three years later total body naevus counts were significantly increased, the median increase being 66 naevi per child (95% confidence interval 57 to 94). The only other problem noted in these children was relatively poor regrowth of scalp hair. CONCLUSION: Children on maintenance chemotherapy for haematological malignancies develop an excessive number of melanocytic naevi. Excessive numbers of melanocytic naevi are the most important risk factor for melanoma in the general population. These children should have periodic skin examinations at their follow up visits, and both child and parent should be educated about clinical features of early melanoma. PMID- 1422360 TI - Female streetworking prostitution and HIV infection in Glasgow. AB - OBJECTIVES: To identify the extent of HIV infection and injecting drug use among female streetworking prostitutes in Glasgow; to estimate the size of the female streetworking prostitute population in the city; and to estimate the number of HIV positive women working as prostitutes on the streets in Glasgow. DESIGN: Observation and interviewing of female prostitutes over seven months in red light district; analysis of saliva samples for presence of antibodies to HIV; capture recapture approach to estimating the size of the female streetworking prostitute population. SETTING: Glasgow. SUBJECTS: 206 female streetworking prostitutes. MAIN OUTCOME MEASURES: Number of women with antibodies to HIV, self reported use of injecting drugs, history of contact with 206 women. RESULTS: Saliva samples were requested from 197 women; 159 (81%) provided samples. Four (2.5%, 95% confidence interval 0.7%-6.3%) of the samples were positive for HIV, all of which had been provided by women who injected drugs. Of the 206 streetworking women contacted 147 (71%) were injecting drug users. About 1150 women are estimated to work on the streets in Glasgow over a 12 month period. CONCLUSIONS: HIV is not as widespread among female prostitutes as many reports in the tabloid press suggest. A greater proportion of female streetworking prostitutes in Glasgow are injecting drugs than has been reported for other British cities. PMID- 1422361 TI - Referral patterns and diagnoses in women attending a urodynamic unit. PMID- 1422362 TI - Diarrhoea during treatment with clozapine: association with lymphocyte count. PMID- 1422364 TI - US health care. I: The access problem. PMID- 1422365 TI - How to implement a no smoking policy. PMID- 1422363 TI - Surgical correction of nearsightedness. PMID- 1422366 TI - Unexplained death in fit young people. PMID- 1422367 TI - Unexplained death in fit young people. PMID- 1422368 TI - Unexplained death in fit young people. PMID- 1422369 TI - Unexplained death in fit young people. PMID- 1422371 TI - Smoking accepted on death certificates. PMID- 1422370 TI - Emergency feeding programmes. PMID- 1422372 TI - Smoking accepted on death certificates. PMID- 1422373 TI - Smoking accepted on death certificates. PMID- 1422374 TI - Predicting preterm delivery. PMID- 1422375 TI - Bovine insulin. PMID- 1422376 TI - Practising intubation on cadavers. PMID- 1422377 TI - Practising intubation on cadavers. PMID- 1422378 TI - Drug resistant tuberculosis. PMID- 1422379 TI - Drug management of ulcerative colitis. PMID- 1422380 TI - Selective serotonin reuptake inhibitors. PMID- 1422381 TI - Predicting mortality from cervical cancer. PMID- 1422382 TI - Predicting mortality from cervical cancer. PMID- 1422383 TI - Quality of life of cancer patients. PMID- 1422384 TI - Oesophageal achalasia mistaken for anorexia nervosa. PMID- 1422385 TI - Delays in thrombolysis. PMID- 1422387 TI - AIDS: guidelines for barbers. PMID- 1422386 TI - False positive salivary HIV test. PMID- 1422388 TI - Reaccrediting general practice. PMID- 1422389 TI - The Health of the Nation. PMID- 1422390 TI - Helmets for pedal cyclists. PMID- 1422391 TI - Transferring myoblasts in Duchenne dystrophy. PMID- 1422392 TI - Where are the guidelines for treating hypertension in elderly patients? PMID- 1422393 TI - Thrombolytic treatment for elderly patients. PMID- 1422395 TI - Learning from "the South". PMID- 1422394 TI - Treating psoriasis with calcipotriol. PMID- 1422396 TI - Magic leaves Bush's AIDS commission. PMID- 1422397 TI - Risk of prostate, ovarian, and endometrial cancer among relatives of women with breast cancer. AB - OBJECTIVE: To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. DESIGN: Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. SETTING: Iceland. SUBJECTS: The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. MAIN OUTCOME MEASURES: Risk of prostate, ovarian, and endometrial cancer among blood relatives of women with breast cancer compared with risk in spouses. RESULTS: The risk of prostate cancer was significantly raised for all relatives (1.5), first degree relatives (1.4), and second degree relatives (1.3) of women with breast cancer. Risk of ovarian cancer was raised for all relatives (1.9) and first degree relatives (1.9) and risk of endometrial cancer was raised for all relatives only (1.9). The risk of prostate cancer was raised if the proband with breast cancer had a first degree relative with prostate cancer. CONCLUSIONS: Coaggregation exists between breast cancer and cancers of the prostate, ovaries, and endometrium. This risk relation is probably based on genes which act by increasing the risk for cancer at these sites. Environmental factors that are common among relatives may also play a part. Continued research is required into pathophysiological mechanisms that could explain these observations. PMID- 1422398 TI - Cost implications of the British Pacing and Electrophysiology Group's recommendations for pacing. AB - OBJECTIVE: To compare present pacing practice with the recommendations recently published by the British Pacing and Electrophysiology Group and to assess the increase in annual budget required to implement these recommendations in a regional cardiothoracic unit. DESIGN: Retrospective analysis of pacemaker implantation for 1991 with calculation of the costs required to implement the group's recommendations based on average 1991 costs of the types of pacing generators and electrode leads used. SETTING: Regional cardiothoracic unit for South West Thames Health Authority. PATIENTS: 433 consecutive patients receiving permanent pacemaker generators: 76 (18%) with sinus node disease; 270 (62%) with atrioventricular block; 25 (6%) with both sinus node disease and atrioventricular block; 59 (14%) with chronic atrial fibrillation and atrioventricular block; and 3 (1%) with carotid sinus or malignant vasovagal syndromes. RESULTS: Only 102 (24%) patients received pacemaker generators recommended by the British Pacing and Electrophysiology Group; however, 355 (82%) patients were older than 65 years, and 264 (61%) were aged 75 or over. The cost of hardware for pacing was 462,885 pounds. Using generators as recommended would have cost 810,525 pounds for "optimal" systems (an increase of 75%) and 710,750 pounds for "alternative" systems (an increase of 54%). These increases would have been considerably reduced by limiting the use of sophisticated pacing to younger patients (aged under 75). Further savings could be made by using the least expensive pacing models available. CONCLUSIONS: Implementing these recommendations should reduce morbidity related to bradyarrhythmia but will lead to major increases in pacing costs. Age and patients' expected activity may be used to select simple pacing systems and thus to contain cost. More research is needed to determine which patient groups will benefit most from complex pacing systems. PMID- 1422399 TI - The role of non-steroidal anti-inflammatory drugs in acute liver injury. AB - OBJECTIVE: To investigate the association between use of non-steroidal anti inflammatory drugs and serious, acute non-infectious liver injury. DESIGN: Retrospective cohort study, cross over design. SETTING: Health records from provincial database in Saskatchewan, Canada, 1982-6. SUBJECTS: 228,392 adults who contributed 645,456 person years. All were either using or had used non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Number and type of prescriptions for non-steroidal anti-inflammatory drugs. Admission to hospital for newly diagnosed acute liver injury. RESULTS: There were 34 admissions to hospital; 16 among subjects currently using non-steroidal anti-inflammatory drugs and 18 among subjects who were not. The incidence rate among current users was 9 per 100,000 person years (95% confidence interval 6 to 15 per 100,000 person years). Subjects currently using non-steroidal anti-inflammatory drugs had twice the risk of newly diagnosed liver injury as those not currently taking these drugs (rate ratio 2.3; 95% confidence interval 1.1 to 4.9) and an excess risk of 5 per 100,000 person years. The age and sex adjusted risk ratio was 1.7 (0.8 to 3.7). The strength of the association increased when only cases with no concomitant use of other hepatotoxic drugs were considered (4.0; 0.9 to 19.0). The rate ratio for people having received one to nine prescriptions was constant. There was no increased risk with long duration of treatment (1.0; 0.3 to 3.5). CONCLUSIONS: There is a small excess risk of serious, acute non-infectious liver injury associated with the use of non-steroidal anti-inflammatory drugs. PMID- 1422400 TI - Generalised pustular psoriasis: response to topical calcipotriol. PMID- 1422401 TI - Angio-edema and urticaria associated with omeprazole. PMID- 1422402 TI - Beware of ciprofloxacin in acute otitis media. PMID- 1422403 TI - Intracoronary papaverine and complete atrioventricular block. PMID- 1422404 TI - Severe hypertension and bronchospasm during disulfiram-ethanol test reaction. PMID- 1422405 TI - Lifestyle advice in general practice: rates recalled by patients. AB - OBJECTIVE: To document how often patients with varying cardiovascular risk levels reported receiving lifestyle advice from general practice. DESIGN: Cross sectional descriptive survey by postal questionnaire. SETTING: 5 general practices in Bedfordshire. SUBJECTS: 4941 people aged 35-64 years who had consulted a general practitioner at least once during the 12 months before completing the questionnaire and who subsequently attended for a health check as part of the OXCHECK trial. MAIN OUTCOME MEASURES: Report of having received advice from a general practitioner or practice nurse about smoking, alcohol consumption, exercise, or diet during the 12 months before completing the questionnaire. Cardiovascular risk assessed by a nurse during structured health check. RESULTS: The overall reported rate of advice was 27% for smoking, 4.5% for exercise, 12% for diet, and 3% for alcohol consumption. Those with unhealthy behaviour profile or at increased cardiovascular risk received more advice--for example, 47% of smokers with a history of cardiovascular disease received advice on smoking. Among those at increased risk, men were more likely than women to receive advice about exercise (11% v 4%, p = 0.04) and alcohol consumption (10% v 4%, p = 0.007), while women received more advice about weight (17% v 23%, p < 0.001). The rate of receiving advice was unaffected by age, marital status, or social class. CONCLUSION: The low rate of lifestyle advice reported by patients implies that more preventive advice could be provided in primary care. PMID- 1422406 TI - US health care. II: The cost problem. PMID- 1422407 TI - Do cycle helmets prevent serious head injury? Cycling without helmets. PMID- 1422408 TI - The argument for helmets. PMID- 1422409 TI - Osteogenesis imperfecta and congenital dislocation of the hip. PMID- 1422410 TI - Osteogenesis imperfecta and congenital dislocation of the hip. PMID- 1422411 TI - Diagnosing congenital dislocation of the hip. PMID- 1422412 TI - Diagnosing congenital dislocation of the hip. PMID- 1422413 TI - Managing the persistent vegetative state. PMID- 1422414 TI - Specialist training and the EC. PMID- 1422415 TI - Specialist training and the EC. PMID- 1422416 TI - Specialist training and the EC. PMID- 1422417 TI - Specialist training and the EC. PMID- 1422418 TI - Asthma and open cast mining. PMID- 1422419 TI - Asthma and open cast mining. PMID- 1422420 TI - Asthma deaths in New Zealand. PMID- 1422421 TI - Asthma deaths in New Zealand. PMID- 1422422 TI - Coloured inhalers. PMID- 1422423 TI - Vitamin K and childhood cancer. PMID- 1422424 TI - Day surgery for cataracts. PMID- 1422425 TI - Exercising for health. PMID- 1422426 TI - Wernicke's encephalopathy and hyperemesis gravidarum. PMID- 1422427 TI - Day surgery for cataracts. PMID- 1422428 TI - Screening, ethics, and the law. PMID- 1422429 TI - Setting up a practice newsletter. PMID- 1422430 TI - Applying for disability living allowance. PMID- 1422431 TI - Developing a district diabetes register. PMID- 1422432 TI - Tobacco advertising. PMID- 1422433 TI - In memoriam of Gavriil A. Ilizarov. PMID- 1422434 TI - Intermetatarsal synostosis after treatment with Ilizarov apparatus: a case report. AB - A transmetatarsal pin was used as part of an Ilizarov apparatus to correct equinovarus deformity of a foot in a 7-year-old patient. The pin created synostosis between the metatarsal bones. The synostosis led to persistent flattening of the transverse arch of the foot, producing a painful gait. To avoid this problem, we recommend that the metatarsal wire be placed only through the first and fifth metatarsals rather than through the neighboring metatarsals. PMID- 1422436 TI - Noninvasive vascular monitoring during limb lengthening. AB - Transcutaneous wires and pins in wire-tension Ilizarov external fixators provide frame stability, transfix and transport bone segments, produce distraction, and stimulate transosseous osteogenesis. Vascular compromise by the transfixing pins and wires is nevertheless an ongoing possibility. Based on earlier studies of a two-phase method of measuring vascular blood blow, noninvasive vascular monitoring was performed on three patients undergoing Ilizarov method limb lengthening. PMID- 1422435 TI - Humeral lengthening and bone transport using the Ilizarov technique. AB - The authors present their results of Ilizarov treatment of eight humeral length deficits and bone defects in seven consecutive patients treated at the Hospital for Joint Diseases. The mean humeral lengthening achieved was 9.8 cm. The lengthening goal was completely achieved in six cases, while two cases achieved over 80% of the desired length. No permanent neurovascular or infectious complication occurred. The authors suggest that the Ilizarov technique is a viable method in treating severe humeral length deficits or bone defects. PMID- 1422437 TI - Pin care using the Ilizarov apparatus: recommended treatment plan in Kurgan, Russia. AB - Differences in the care of the pins used in association with the Ilizarov apparatus and technique are found in various countries and institutions. During a recent visit to the Ilizarov Institute in Russia, the methods of caring for the Ilizarov pins were extensively investigated and documented. The U.S. infection rate at pin sites has been reported to be nearly 10%. No specific infection rate has been reported from Russia. What constitutes an infection at the Ilizarov Center in Kurgan was investigated, as were methods of treatment. Our conclusion is that pin care in Russia is conducted under a more vigorous and stringent regimen, but less often, than in the United States. Soviet record keeping is different, and therefore the infection rates cannot be compared. In Kurgan, specific diligence is exercised in addressing the problems at each pin site. Treatment is directed toward alleviating these problems. PMID- 1422438 TI - Rigidity of half-pins for the Ilizarov external fixator. AB - The success of the Ilizarov technique is due to the combination of the biomechanics of its external fixator and the biology of distraction osteogenesis. The stability and stiffness of the conventional Ilizarov fixator is attributed to its use of a K-wire cross structure. The disadvantages of this structure include pain, and possible neurologic and vascular injuries when the wires are introduced into crucial neurovascular areas, as well as increased frame complexity and construction. Reducing the number of wires decreases these problems, but also decreases the stiffness of the system. Hybrid (wire and half-pins) Ilizarov fixators and half-pin fixators are also being used in an attempt to alleviate these problems. Half-pins have been described by Fleming et al. and Green as causing minimal transfixation of the surrounding soft tissues and capable of and being inserted into anatomically safe areas. The stiffnesses of the hybrid systems have not been measured. This study reports on the stiffness of different wire and half-pin systems that were biomechanically tested in axial loading, anterior-posterior bending, medial-lateral bending, and torsional loading. The results demonstrated that the conventional Ilizarov fixator with wires possesses a high axial stiffness, whereas the fixator with half-pins possesses higher stiffness under bending and torsional loads. To obtain adequate stability, the use of hybrid Ilizarov frames with one wire and two or more half-pins (5 or 6 mm in diameter), or larger half-pin frames (5 or 6 mm) with three pins is recommended. PMID- 1422439 TI - The theoretical application of inclined hinges with the Ilizarov external fixator for simultaneous angulation and rotation correction. AB - The mathematical concepts of single-cut osteotomies for simultaneous correction of angulation and rotation have been adapted and simplified for gradual distraction-osteogenic correction with the Ilizarov external fixator. Validation studies were performed analytically, using a solid modeling analysis, and experimentally with an Ilizarov external fixator mounted on a wood dowel. The resultant equations have been simplified and are easy to use. Starting from the hinge which would correct the angulation, the axis must be reoriented in the horizontal plane by half the rotation deformity (R/2) and given an inclination slope equal to the rotation divided by the angulation (R/A). PMID- 1422440 TI - Control of interfragmentary micromotion in Ilizarov distractional osteogenesis. AB - Growth of the regenerate is affected by various factors during the course of Ilizarov distractional osteogenesis. One of the chief biomechanical factors that influences the quality and rate of bone formation is fixator stiffness. A four ring Ilizarov apparatus was configured around a synthetic tibia. In a series of trials involving a uniform axial load, different transfixing wire tensions, and the separation of paired proximal and distal rings, fragment displacement was measured. Preliminary results suggest that the effect produced by the distraction of ring pairs on interfragmentary micromotion is as significant as pretensioning of the wires. PMID- 1422441 TI - 3rd annual meeting of the Association for the Study and Application of the Methods of Ilizarov. Charleston, South Carolina, October 4, 1991. Abstracts. PMID- 1422442 TI - Pelvic support femoral reconstruction using the method of Ilizarov: a case report. AB - A 15-year-old boy presented with a fixed, irreducible congenital dislocation of the hip associated with other multiple lower extremity growth disturbances secondary to neonatal multifocal osteomyelitis. The affected hip had very limited abduction, and the patient had a very severe Trendelenburg gait secondary to the dislocation. The hip was reconstructed according to the Ilizarov method, by a combination of maximum proximal femoral adduction osteotomy in the subtrochanteric region and distal femoral corticotomy, to permit the gradual realignment of the knee into the new weight-bearing axis produced by the proximal osteotomy. Total fixation time for the femoral reconstruction was two months. Five months after removal of the apparatus, the patient was returned to full function with a remarkably improved gait. PMID- 1422443 TI - [The effect of digoxin on the cerebral blood flow in rabbits]. AB - Hydrogen clearance was used in chronic experiments on 10 unrestrained rabbits to study the influence of digoxin (0.1 mg/kg, i. v.) on the time course of changes in the local brain circulation in the sensorimotor, temporal and optic cortex. It has been revealed that digoxin is capable of exerting varying influence on circulation in the above-mentioned regions. Potential mechanisms of the data obtained are under discussion. PMID- 1422444 TI - [The effect of the antioxidant ionol as a liposome component on the function of the isolated and ischemic heart]. AB - The anti-ischemic and toxic effects of different doses of the antioxidant ionol (butyl hydroxytoluene, BHT) introduced into the Krebs-Henseleit medium composed of monolayer liposomes of egg phospholipids before or 30 minutes after total ischemia of the heart were studied on a model of perfusion of isolated Wistar rat heart by the method of Langendorff-Fallen. It has been demonstrated that ionol, after its addition to the perfusate in the preischemic period, exerts an anti ischemic effect in concentrations of 10(-6), 3 x 10(-6) and 10(-5) M; in the postischemic period, in concentrations of 3 x 10(-6) and 10(-5); the protective effect of ionol in the postischemic period is less pronounced. In higher doses (3 x 10(-5) and 10(-4) M) ionol produces a toxic action which is more remarkable and is less reversible in respect to the ischemized than to the nonischemized heart, and is realized rather through the dysfunction of heart muscle relaxation. The conclusion is drawn that there is a possibility of using ionol in doses of 10(-6) to 10(-5) M as a constituent of liposomes for addition to perfusion, conservant and cardioplegic solutions as an anti-ischemic remedy. PMID- 1422445 TI - [Calcium and calcium-channel blockers in the healing of an experimental myocardial infarct]. AB - It has been shown in experiments on 36 dogs with experimental myocardial infarction (MI) that the effect of calcium and blockers of calcium channels largely depends on the initial condition of reactivity and is realized via changes in lipid peroxidation (LPO). In MI, calcium enhances necrotic processes whereby aggravating disorders in its healing in case of high reactivity and returns them to normal, thus contributing to optimization of its healing in animals with low reactivity. Calcium channels blockers attenuate necrotic processes associated with MI and lead to its better healing in the presence of high reactivity and aggravate disorders in its healing in animals with low reactivity. Consideration of the body reactivity, the differentiated use of calcium drugs and calcium channels blockers should be regarded as an effective approach to optimization of the healing of complicated forms of MI. PMID- 1422446 TI - [The effect of the surface-active substance proxanol on the ischemic myocardium]. AB - The anti-ischemic effect of a 4% proxanol solution (intravenous injection in a dose of 10 ml/kg 60 min after occlusion) was compared with that of a salt solution in experimental acute ischemia of dog myocardium, induced by partial occlusion of the anterior descending branch of the left coronary artery. Overall estimation of the effect of SAS infusion has demonstrated that this drug has a beneficial effect on hemorheology (decreases blood viscosity and vascular resistance, increases coronary blood flow), stabilizes oxygen supply of the myocardium and lowers the extent of its ischemia-induced damage (eliminates ST segment depression). However, the cardiodepressive action of proxanol does not allow for compensation of the ischemia-induced decrease in myocardial contractility and pump function of the heart. PMID- 1422447 TI - [The correlation of the catecholamine and electrolyte balance in vascular tissue in acute toxic hepatitis and its pharmacotherapy]. PMID- 1422448 TI - [The interaction of the Ca2(+)-channel blocker verapamil with cardiac glycosides in the rat kidney]. AB - Strophanthine (0.1 mg/kg, i. v.) and digoxin (0.1 mg/kg, i. v.) increase blood supply of the cortex and medullary layer of the kidneys of anesthetized rats and significantly raise excretion of water and sodium by the kidneys. Verapamil, a blocker of Ca(2+)-channels (0.25 mg/kg, i. v.) attenuates the increment of the blood flow in the internal zone of the cortex and external zone of the medullary layer but does not prevent the rise of diuresis and excretion of sodium with urine under the action of the above-indicated drugs. The conclusion is drawn that realization of the vasodilatory effect of cardiac glycosides in the kidneys is partially connected with a lowering of the content of Ca2+ in myofibrils whereas formation of their tubular effect does not depend on the changes in Ca2+ concentration in nephron cells. PMID- 1422449 TI - [The effect of a new drug form for the intravenous administration of vitamin K1 on the blood coagulation system]. AB - In rabbits with experimental hypocoagulation induced by phenylin, the use of a new dosage form of vitamin K1 for intravenous injections in does of 1 and 5 mg/kg led, in contrast to vicasol in a dose of 0.4 mg/kg, to an increase of the prothrombin index after 2 hours and to its complete normalization after 4 hours. Intravenous injection of vitamin K1 into intact animals did not entail any changes in the activated partial thromboplastin time, thrombin and prothrombin time, in the content of fibrinogen and products of its biotransformation, antithrombin III activity, and fibrinolytic activity or in the count of platelets and their aggregation capacity. PMID- 1422450 TI - [The effect of dibunol on lipid peroxidation and the alpha-tocopherol level in the lungs of rats with acute blood loss]. AB - Experiments on linear male rats were made to study the pathophysiological mechanism of the synthetic antioxidant dibunol on the levels of primary and end products of lipid peroxidation (LPO) and of alpha-tocopherol (TP) in the lungs in acute hemorrhage. Dibunol in a dose of 120 mg/kg injected 5 min after the hemorrhage inhibited LPO to the level in intact animals and raised the content of TP to the level seen in operated animals without any hemorrhage. The conclusion is drawn about a possibility of using dibunol for correction of disturbed pulmonary metabolism in urgent conditions associated with blood loss. PMID- 1422451 TI - [The effect of solubilized alpha-tocopherol acetate on resistance to experimental physical loading]. AB - A single intravenous injection of solubilized alpha-tocopherol acetate to Wistar male rats in doses of 25, 50 and 100 mg/kg noticeably increased the animals' working capacity. The stimulation effect appeared 18 hours after the injection and was observable for two weeks. Utilization of glucose reserves in bioenergy supply of muscle activity has been shown. The maintenance of the action for such a long time may be accounted for by high metabolic stability of solubilized alpha tocopherol acetate. PMID- 1422452 TI - [The antioxidant activity of bis-quaternary ammonium compounds of the methylene series]. AB - Experiments on albino rats were made to reveal antioxidant activity of bisquaternary ammonium compounds of the methylene series (ethonium, thionium and dodeconium). It is determined by the enhancement of superoxide anion radicals neutralization and splitting of lipoperoxides. PMID- 1422453 TI - [The mechanism of action of dimephosphon]. AB - It has been established in experiments on rats that the 7-day administration of dimephosphon per os increases blood levels of total mercapto groups and glutathione, changing the correlation of its forms in favour of the oxidized ones. This course of dimephosphon administration reduces blood concentration of lipid peroxidation products. The significance of these mechanisms in realization of the pharmacological effects of dimephosphon is under discussion. PMID- 1422454 TI - [The comparative action of isoniazid, rifampicin and ethambutol on liver function]. AB - It has been established in experiments on white rats that antituberculous drugs (isoniazid, rifampicin, ethambutol) given in toxic doses affect the liver, its membranes and organelles, inhibit bile production and bioenergy. This is supported by activation of aspartate and alanine aminotransferases, (ALT and AST), alkaline phosphatase in blood serum and acid phosphatase in the liver, by a decrease of the activity of Na(+)-, K(+)-ATPase, succinate dehydrogenase and cytochromoxidase in the liver, lowering of the rate of bile secretion, excretion of bile acids, bilirubin and cholesterol with bile. Provided the drugs are administered in combination, the hepatotoxicity rises, particularly in combination of isoniazid with rifampicin, and especially as isoniazid is combined with rifampicin and ethambutol. PMID- 1422455 TI - [The effect of ketoconazole on the cholesterol content of the blood serum lipoproteins and bile in experimental hypercholesterolemia]. AB - Inclusion of ketonazole (in a daily dose of 400 mg/kg for 8 days) into the diet of intact and cholesterol-fed (5% dietary cholesterol) rats produced a respective 20- and 30-percent lowering of cholesterol content in blood serum. In all the animals, the hypocholesterolemic effect of ketoconazole was realized via a decrease of the concentration of very low and low density lipoproteins. Ketoconazole also gave rise to a reduction of the concentration of cholesterol and bile acids in bile of the intact rats and of cholesterol in bile of the cholesterol-fed animals. PMID- 1422456 TI - [The cytogenetic effects of antitumor preparations with different mechanisms of action]. AB - The cytogenetic effects of antitumor drugs with different action mechanism on the genetic structure of bone marrow hemopoietic cells were studied in experiments on CBA mice. It has been shown that single injections of doxorubicin (6 mg/kg), vinblastin (2.2 mg/kg), cyclophosphamide (250 mg/kg) and continuous administration of doxorubicin (0.95 mg/kg), vinblastin (0.24 mg/kg), cyclophosphamide (27 mg/kg) in 1/10 LD50 x 10 induce the formation of bone marrow cells with cytogenetic damage and peripheral red blood cells with micronuclei. The cytogenetic damage of hemopoietic tissue may be detectable 1-3 months after cytostatic influence. PMID- 1422457 TI - [The pharmacokinetics and pharmacodynamics of pentoxifylline (trental) in the third pregnancy trimester]. AB - As a result of studies into the pharmacokinetics of pentoxyfillin, no significant differences were established in the magnitudes of its non-model parameters in normal pregnancy and chronic placental insufficiency. However, there were differences in the metabolite formation rate in the groups under study. Distinctions were detected in the antiaggregation effect of pentoxyfillin. They consisted in a slower recovery of platelet aggregation parameters to the initial values in the first group examined. There was no good agreement between the concentrations of pentoxyfillin, its major pharmacologically active metabolite in blood plasma of pregnant women and the antiaggregation effect, which reaffirms the indirect action of this drug on platelets. PMID- 1422458 TI - [The role of endogenous K+ in realizing the protective action of M-cholinolytics in chlorophos poisoning]. AB - The protective effect of M-cholinolytics during the poisoning of mice with chlorophos or exogenous acetylcholine is characterized by certain specific features. An attempt to reproduce the cholinolytic effect during poisoning by organophosphorus compounds was successful in case where the intoxication by a direct cholinomimetic was carried out in the presence of KCl solution or where the animals' poisoning was preceded by administration of voltage-dependent K+ channel blockers. The conclusion is made that the increased concentration of extracellular K+ occurring as the result of poisoning with organophosphorus compounds may play a role in the mechanism of the protective action of M cholinolytics in chlorophos poisoning. PMID- 1422459 TI - [The correction of disorders in the pharmacodynamics of drugs metabolized in the liver in the postnatal ontogeny of rats with acute hepatitis]. AB - It has been established in experiments on 30 day albino rats that in acute hepatitis, the pharmacodynamics of the test drugs hexenal, amidopyrine and ethylmorphine metabolized in the liver is considerably potentiated. In contrast to silibor, phytin and zixorine, experimental therapy with benzonal brings about a complete recovery of the pharmacodynamics of the drugs under study. It is believed that benzonal holds promise in pediatrics as a remedy that restores the detoxifying potency of the liver. PMID- 1422460 TI - [The effect of antioxidants on the fast burst of Fe2(+)-induced chemiluminescence]. AB - A new micromethod for measuring the intensity of free radical oxidation reactions, based on an analysis of "fast flash" of iron-induced chemiluminescence parameters has been designed. The optimal concentration parameters of the reaction system have been determined. The effects of the antioxidants mexidol, probucol sodium dibunat and fenoxan have been examined in vitro. PMID- 1422461 TI - [An electromyographic method for determining the antihypoxic activity of preparations]. AB - To measure drug antihypoxic activity, an electromyographic method was worked out. The main idea of the method is to estimate the influence of these substances on the amplitude of slow electric waves of smooth muscles on an isolated strip of rat small intestine in situ. This parameter whose value directly depends on tissue pO2 was recorded under the conditions of artificial ischemia of the intestinal strip. Circulatory hypoxia was simulated by the clamping of mesentery vessels, and the time was determined, during which the amplitude of slow electric waves reduced to 1/3 of the initial value in control animals and rats treated beforehand with the drugs under study. Antihypoxic activity of the drugs was calculated as difference in these time intervals between experiment and control, given in per cent. PMID- 1422462 TI - [The pharmacological effect of nonsteroid anti-inflammatory agents and their interaction with blood plasma proteins]. PMID- 1422463 TI - [The chronopharmacotherapy of diseases]. PMID- 1422464 TI - [An assessment of the individual sensitivity of Wistar rats to the development of morphine dependence]. AB - A search was made for behavioral and physiological indicators which could serve predictors of the individual sensitivity of Wistar rats to the development of physical morphine dependence. Animals with high sensitivity to the development of dependence initially demonstrated intensive ambulation and low motor rearing in the "open field" and had low nociception. Stable animals exhibited high ambulation and motor rearing with insignificant grooming activity as compared to other rats. It has been revealed that rats sensitive to the development of dependence demonstrate higher anxiety in the Vogel test as compared to the stable ones. The findings obtained allowed one to derive a number of equations to predict Wistar rats' individual sensitivity to the development of physical morphine dependence. PMID- 1422465 TI - Multiple cytogenetic aberrations in squamous cell carcinomas of the head and neck. AB - Chromosomal abnormalities in short term cultures have been investigated in 10 squamous cell carcinomas of the head and neck. Of these tumours, three demonstrated clonal chromosomal abnormalities, two showed random abnormalities and 5 patients' tumours had normal karyotypes. The 5 patients with aberrant karyotypes were all from previously treated tumours, of these, 4 patients had received radiotherapy and 1 surgery. On analysis of the three clonal tumours, two were found to be polyclonal, each with five separate clones. 116 breakpoints were demonstrated from the clonal data of these tumours, and all of the chromosomes were involved, apart from number 18. In this study we found three or more breakpoints at sites 1p36, 9q32 and 11q23. 1 of the patients investigated showed a clonal abnormality involving a breakpoint at the 11q13 site, with a further 2 patients having breakpoints at 1p22--sites previously reported to have marked clustering of cytogenetic abnormalities in oral cancer patients. Only further studies will demonstrate whether the breakpoints found are of clinical significance. PMID- 1422466 TI - Referral patterns of patients with oral squamous cell carcinoma, Australia. AB - Early diagnosis is an important factor affecting the prognosis of patients with oral cancer. Delays in diagnosis have been variously reported as being linked to the patient, the clinician or both. The purpose of this study was to investigate the referral patterns of patients with oral cancer by medical and dental practitioners, in order to assess the delays in diagnosis and to establish the reasons for these delays. 51 consecutive patients diagnosed with oral mucous membrane squamous cell carcinoma were retrospectively reviewed. In this study it was found that over one-third of the patients (38%) delayed seeking professional advice for more than 3 months after first being aware of the lesion. Initial delays in diagnosis of oral cancer was identified in one-third of the cases (17 patients), with antimicrobial medications prescribed and denture adjustments constituting the most frequently administered inappropriate therapy. General medical practitioners were more likely to encounter and refer patients with more advanced (T4) primary oral cancers than their dental colleagues. The findings of this study raise the concern that lack of patient awareness and inappropriate clinical management prevails in a community that should be better informed. PMID- 1422467 TI - Nass use, cigarette smoking, alcohol consumption and risk of oral and oesophageal precancer. AB - In a cross sectional study, conducted in Uzbekistan, an area with a high incidence of oral and oesophageal cancer, 1569 men were interviewed regarding use of nass quid, cigarette smoking and alcohol drinking. All subjects in the study had an oral examination, and oesophagoscopy was performed in 1344 men. Nass use and cigarette smoking emerged as independent risk factors for oral leukoplakia. The prevalence odds ratio (OR) for life-time nass intake equivalent rose from 1.0 in never-users to 5.17 [95% confidence interval (CI), 3.10-8.61] in the highest category; for total pack-years of cigarettes smoked the risk rose from 1.0 in never-smokers to 10.03 (95% CI, 4.9-20.6) in the highest category. There was a significant trend in risk (P < 0.001), for both factors. In the group with oral leukoplakia, the effect of nass use and cigarette smoking appeared to be additive. Cigarette smoking was also found to be an independent risk factor for oesophageal lesions and was significantly associated with chronic oesophagitis. The risk of chronic oesophagitis in the group with the highest pack-years of cigarettes smoked was approximately double that among non-smokers [Odds ratio (OR) = 2.47; 95% CI 1.34-4.56]. There was a weak association between nass use and oesophageal pathology: the highest life-time intake equivalent was associated with an OR of 1.56 (95% CI 1.09-2.23). Alcohol intake was not found to be independently associated with the presence of oral and oesophageal precancerous lesions. PMID- 1422468 TI - Delay in diagnosis of oral squamous cell carcinoma; a report from The Netherlands. AB - The referral pattern, patients' and doctors' delay of a limited number of 50 patients suffering from oral squamous cell carcinoma have been investigated. The majority of the patients consulted the family doctor as the first source of help. The mean patients' and doctors' delay was 103 and 22 days, respectively the median being 35 and 11 days, respectively. The gender, dental status, site and tumour size did not show a significant correlation with the delay. Measures directed to the early detection of oral cancer should place special emphasis on the patients' delay. PMID- 1422469 TI - Hodgkin's disease involving the gingiva in AIDS. AB - Non-Hodgkin lymphomas are a recognised complication of AIDS and may involve the oral cavity. However, no case of Hodgkin's disease affecting the oral cavity in AIDS appears to have been recorded. We report a male homosexual with AIDS and Hodgkin's lymphoma, who presented with gingival involvement. PMID- 1422470 TI - Relationship of chemotherapy-induced mucositis and myelosuppression in hamsters. PMID- 1422471 TI - Screening for oral cancer and precancer. PMID- 1422472 TI - Viruses and oral squamous carcinoma. PMID- 1422473 TI - Recent papers related to oral oncology. PMID- 1422474 TI - Smoking, alcohol, dentition and diet in the epidemiology of oral cancer. AB - This matched case-control study was conducted in Western New York. The smoking, alcohol consumption, dental hygiene and diet of 290 cases were compared with those of 290 sex-, age-, and neighbourhood-matched controls. The results confirm earlier findings that cigarette smoking and alcohol consumption impart substantial risk of oral cancer. The results also confirm that poor oral hygiene increases the risk of oral cancer, although this effect is much smaller than those of cigarette smoking and alcohol consumption. The results suggest that, of macronutrients, intake of fat is more likely than those of protein or carbohydrate to be related to risk. Of micronutrients, calcium, sodium, riboflavin and retinol are associated with risk, while thiamin, niacin, and dietary fibre are associated with decreased risk. Although patterns of dietary effects are discernable, these effects are in general much weaker than are those of smoking and alcohol consumption. PMID- 1422475 TI - Hepatic veno-occlusive disease--liver toxicity syndrome after bone marrow transplantation. AB - Hepatic veno-occlusive disease (VOD) is the most common life threatening complication of preparative-regimen-related toxicity for bone marrow transplantation (BMT). The frequency of VOD varies greatly, from 1-2% in centers performing pediatric BMT for thalassemia to over 50% in some centers doing BMT for hematologic malignancy. The term liver toxicity syndrome is a clinicopathologic definition which encompasses the range of histopathology within the hepatic venules and surrounding sinusoids and hepatocytes. These histologic abnormalities are statistically associated with a clinical syndrome of jaundice, ascites, and painful hepatomegaly developing early post-transplant. Newer modalities which may aid accuracy are transvenous liver biopsy along with determination of the gradient between the wedged and free hepatic venous pressures, and measurement of blood coagulatory components, particularly protein C levels. Analyses of clinical risk factors for VOD are confounded by lack of a clear hierarchy of risk when comparing heterogeneous patient populations, the methods of patient selection and choice of controls, and whether analysis is univariate or multivariate. Prospective multivariate analyses indicate that the risk of developing liver toxicity is independently correlated with intensity of conditioning therapy, pre-transplant viral hepatitis, use of antimicrobial therapy with acyclovir, amphotericin, or vancomycin (reflecting fever), and mismatched or unrelated allogeneic marrow grafts. These analyses plus morphologic and biochemical data support the hypothesis that VOD is caused by cytoreductive injury to hepatocytes and endothelium in zone three of the liver acinus, and in turn strongly influenced by factors which induce the release of tumor necrosis factor-alpha (TNF-alpha) leading to enhancement or activation of coagulation with obstruction of hepatic sinusoids and venules. Pharmacokinetic measurements of busulfan as a conditioning agent demonstrate a correlation between high steady state busulfan levels and liver toxicity and suggest that safer and/or more efficacious plasma busulfan concentrations can be obtained by making individual dose adjustments and by changing the schedule of administration. Conservative therapy of severe VOD, including the use of peritoneal-pleural shunts for relief of ascites, is unsatisfactory. Results from prophylactic studies aimed at preventing VOD by heparin or prostaglandin E1 indicate considerable differences with toxicity and efficacy. Use of the TNF-alpha blocker, pentoxifylline, has also shown promise in lessening VOD. A statistical model which predicts patients likely to have an unfavorable outcome from VOD has been used to select premorbid patients for promising new therapeutic modalities, such as recombinant tissue plasminogen activator. PMID- 1422476 TI - Antimitochondrial antibodies in patients with chronic graft-versus-host disease. AB - Chronic graft-versus-host disease (cGVHD) and primary biliary cirrhosis (PBC) have many clinical and laboratory features in common. These include scleroderma or lupus erythematosus-like skin lesions, a Sjogren-like sicca syndrome, cholestatic liver disease and a variety of serological autoimmune phenomena. Furthermore, liver histology in both diseases is characterized by lymphocytic infiltration of the portal fields and destruction of small bile ducts. We investigated whether there were also parallels between both diseases in incidence and characteristics of antimitochondrial (AMA) and other autoantibodies. Sera from patients with cGVHD (n = 11, group 1) were examined by immunofluorescence (IFL) and immunoblot (IBL), and the results were compared with sera from patients without cGVHD (n = 21, group 2) and after autologous BMT (n = 16, group 3). In group 1 AMA was detected by IFL in one and by IBL in nine of 11 (81%) patients. Group 2 and 3 patients were AMA-negative by IFL and AMA positive by IBL in statistically lower incidence of 19% and 6% (p less than 0.001), respectively. cGVHD-associated AMA recognized a spectrum of mitochondrial proteins, the most frequent being molecules of 63/60 kD and 22 kD. Follow-up studies showed a temporal correlation between the emergence of AMA and the clinical occurrence of cGVHD. We conclude that patients with cGVHD have a high incidence of AMA similar to patients with PBC, but the reaction pattern of AMA differs between the diseases. The presence of AMA in cGVHD further emphasizes the concept that both diseases may have a related pathogenetic background. PMID- 1422477 TI - Fractionated TBI and methotrexate-cyclosporin do not seem to increase relapses in BMT for first chronic phase CML patients: results of a single centre study. AB - Fractionated total body irradiation (FTBI) and methotrexate-cyclosporin A(MTX CSA) have been found useful in reducing interstitial pneumonia (IP) and acute graft-versus-host-disease (GVHD) in bone marrow transplantation patients, but an increase in relapse rate has been observed by some authors when these strategies are used. To evaluate this relapse risk, we performed a retrospective analysis in 24 consecutive first chronic phase chronic myeloid leukemia patients who received an HLA-identical non-T cell-depleted graft in a single institution. All were conditioned with cyclophosphamide plus FTBI (12 Gy in six fractions delivered twice daily for 3 days) (CY-FTBI) and received MTX-CSA as GVHD prophylaxis. Serial hematologic and cytogenetic bone marrow analysis were performed at least three times (days +30, +100, +360) and at variable intervals thereafter in long term survivors. Actuarial probabilities of developing IP and acute GVHD greater than or equal to II were respectively 5.9% and 44.2%, with a GVHD-associated mortality of 33%. Four-year actuarial relapse and disease-free survival rates were 7.7% and 48.2% respectively. No exclusively cytogenetic relapses were observed. Our results suggest that CY-FTBI and MTX-CSA are not associated with an increase in relapse rate in 1CP-CML patients. PMID- 1422478 TI - TCR gamma/delta positive lymphocytes after allogeneic bone marrow transplantation. AB - Peripheral gamma/delta+ T cells were studied in patients following allogeneic bone marrow transplantation (BMT) by indirect immunofluorescence utilizing two monoclonal antibodies (G1 and A13) able to recognize the two major subpopulations (V delta 2+ and V delta 1+, respectively) of these cells. We found that the relative percentage of 'total' (gamma/delta+ T lymphocytes) (V delta 2 + V delta 1 positive cells), and particularly of G1+ (V delta 2+) cells, in CD3+ lymphocytes was higher in transplanted patients, and especially in those presenting with acute graft-versus-host disease (aGVHD), than in normal controls. This finding was confirmed by the analysis of the V delta 2+/V delta 1+ cell ratio which was again significantly higher in patients with aGVHD as compared to controls. Similarly, the absolute number of 'total' gamma/delta+ and V delta 2+ cells was also significantly increased in patients with aGVHD. TCR gamma/delta+ T cells increased as a function of time after BMT reaching a plateau value at about day 60 post-BMT. When patients were stratified for the presence or absence of aGVHD this correlation was maintained only for patients with aGVHD. Finally, most V delta 2+ cells expressed surface T cell activation markers such as CD25 (IL-2 receptor) and DR (MHC class II) antigens. Our results suggest a possible involvement of gamma/delta+ T cells and particularly of V delta 2+ cells in the clinical and immunological events (aGVHD) occurring after allogeneic BMT. PMID- 1422479 TI - Host origin of bone marrow fibroblasts following allogeneic bone marrow transplantation for chronic myeloid leukemia. AB - We investigated the origin of the fibroblastic compartment of stromal hematopoietic microenvironment in eight chronic myeloid leukemia (CML) patients following allogeneic BMT. At the time of the study, all eight CML patients showed complete and long-lasting (14-87 months) engraftment of donor hematopoiesis and absence of clonal Ph-positive hematopoiesis. The study was carried out using in vitro amplification of informative DNA sequences: a Y chromosome specific DNA fragment in three patients who received a sex-mismatched allograft, and locus D1S80, a variable number of tandem repeats polymorphism, in five patients who received a sex-matched allograft. In all cases bone marrow fibroblasts were of recipient origin. These data indicate that with current BMT procedures the stromal compartment of hematopoiesis is not transplantable in humans. PMID- 1422480 TI - Predictive value of flow cytometric analyses of blast cells in assessing the phenotype of the leukemia colony-forming cell (L-CFC) population in acute myeloid leukemia. AB - Acute myeloid leukemia (AML) blast cells (BC) express antigens that are commonly found on their normal counterparts. The leukemia colony-forming cell (L-CFC) subpopulation, identified by its ability to form leukemia colonies in vitro, is thought to be the stem cell population that produces BC. To ascertain the association between myeloid antigens on the BC and the L-CFC from the same patient, we compared the expression of CD14, CD15, CD33, p124 and HLA class I from 17 cases of AML. These particular myeloid antigens were studied because they are suitable targets in purging bone marrow for autotransplantation. We found no significant difference in the expression of CD14, CD15, CD33, and HLA class I on the BC and L-CFC from the same patient, although we observed considerable heterogeneity among different AML cases. Analysis of the progenitor cell antigen p124 revealed significant within-patient differences on the BC and L-CFC (p = 0.007), with a greater tendency for expression on the L-CFC. This heterogeneity may be due to differences in maturation stage of the L-CFC and BC. This information is important when L-CFC phenotype is used to determine the appropriate selection of antibodies for purging of residual disease in the context of auto-transplantation. PMID- 1422481 TI - Pneumocystis carinii pneumonitis following bone marrow transplantation. AB - Pneumocystis carinii pneumonitis (PCP) can occur in immunocompromised hosts, especially AIDS and cancer patients. Although recent research has focused on PCP in AIDS patients, few studies have described the clinical presentation of PCP in recipients of bone marrow transplantation (BMT). Between 1976 and 1991, of 1454 BMT patients at the University of Minnesota, PCP was documented in only 19. Eighteen of these had not been receiving PCP prophylaxis. Patients presented with a brief period (2-10 days) of symptoms including dyspnea, cough, and fever in greater than 75% of patients, but had only scant abnormal physical findings. Chest X-rays showed bilateral infiltrates in 58% of all patients, though 15% had no or minimal X-ray findings. Bronchoscopic alveolar lavage confirmed the diagnosis most often, but 13% of lavages were negative and required biopsy for the diagnosis. High dose trimethoprim-sulfamethoxazole was the initial treatment for 84% of the patients though 25% of these patients were later switched to pentamidine due to poor response or hypersensitivity reactions. Despite prompt diagnosis and therapy, overall survival was poor, with only 37% of patients surviving pneumonitis. Patients developing PCP less than 6 months post-BMT had greater mortality (89%) versus only 40% in later onset PCP (p less than 0.0001). Despite this better survival in the late-onset PCP cohort, the development of pneumonitis in these patients underscores the necessity for continued PCP prophylaxis beyond 1 year in some patients. Ongoing immunocompromise and need for prophylaxis should be appreciated in patients with graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422482 TI - Bone marrow transplants using volunteer donors--recommendations and requirements for a standardized practice throughout the world. The Executive Committee of the World Marrow Donor Association. AB - The World Marrow Donor Association, originally designated the Collaborative Marrow Donor Program, was established in 1988 to address problems and to establish guidelines in relation to 'international' bone marrow transplants- transplants in which the donor is in one country and the patient in another country. This paper sets out recommendations and requirements governing clinical indications, ethical considerations, selection and counselling of donors, collection and transportation of marrow and financial and insurance related issues. PMID- 1422483 TI - Molecular remission occurring after donor leukocyte infusions for the treatment of relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. AB - Donor leukocyte infusions were administered to a patient who had relapsed with chronic myelogenous leukemia after having failed two successive HLA-matched allogeneic bone marrow transplants. Serial cytogenetic, restriction fragment length polymorphism, and polymerase chain reaction studies of the patient's marrow and blood after receiving donor leukocyte infusions revealed disappearance of the leukemic clone and the establishment of complete donor chimerism. An antileukemic response in this patient occurred initially in the absence of clinically evident graft-versus-host disease (GVHD), but complete eradication of the leukemic clone did not occur until after the onset of GVHD. The patient is now 48 weeks post infusion and remains in complete remission. This case demonstrates that leukocyte infusions are an effective form of adoptive immunotherapy which can result in a sustained molecular remission. PMID- 1422484 TI - Bronchiolitis obliterans organizing pneumonia as a complication of allogeneic bone marrow transplantation. AB - We report a patient who underwent two allogeneic bone marrow transplants for chronic myelogenous leukemia, initially in 1984 and again after relapse in 1990, who developed an identical pulmonary syndrome at a similar interval following each transplant. The patient presented with a non-productive cough, bilateral inspiratory crackles, and multiple patchy infiltrates on chest X-ray. Pulmonary function testing revealed a restrictive abnormality but no obstructive defects. The appearance of this pulmonary disorder after each transplant coincided with the development of chronic graft-versus-host disease. In both instances, this pulmonary syndrome completely reversed with corticosteroid therapy. The patient's chest computed tomographic scan and lung biopsy specimens were consistent with the diagnosis of bronchiolitis obliterans with organizing pneumonia (BOOP). While bronchiolitis obliterans has been reported following allogeneic transplant, BOOP has not previously been reported in this setting. PMID- 1422486 TI - On difficulties of interpreting cyclosporine blood levels. PMID- 1422485 TI - Complete recovery of sperm production following bone marrow transplantation for leukemia. PMID- 1422487 TI - Comparative cost of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukaemia in first remission. AB - We compared the direct costs of allogeneic bone marrow transplantation (Allo BMT), autologous bone marrow transplantation (Auto-BMT) and chemotherapy (Chemo) in 40 adult patients under the age of 55 years with acute myeloid leukaemia (AML) in first complete remission (CR). Fourteen patients were treated with Allo-BMT, 11 with Auto-BMT and 15 with Chemo. These patients, who were part of two cooperative consecutive trials enrolling a total of 196 patients (BGM 84 and BGMT 87 studies), were those who were treated in the CHR Bordeaux and achieved CR after induction chemotherapy. Cost accounting extended over a maximum period of 5 years. The average cost of the procedure for a mean follow-up of 2 years and excluding the cost of treatment after relapse which eventually occurred was significantly higher for the Allo-BMT group (FF 392,724) and the Auto-BMT group (FF 393,461) than for the group that received Chemo (FF 128,947) (p < 0.00001). The average cost for the treatment of relapse was estimated at FF 266,436, irrespective of the previous treatment. The total cost, including the estimated cost of relapse according to its probability of occurring calculated from the original population, was significantly higher for the Allo-BMT group (FF 424,696; p < 0.01) and the Auto-BMT group (FF 505,364; p < 0.0001) than for the Chemo group (FF 304,846).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422488 TI - Clinical characteristics of chronic cutaneous graft-versus-host disease in Japanese leukemia patients after bone marrow transplantation: low incidence and mild manifestations of skin lesions. AB - We investigated the incidence of chronic graft-versus-host disease (GVHD) and skin and oral lesions in chronic GVHD in 90 Japanese leukemia patients surviving over 100 days after bone marrow transplantation (BMT) from HLA-compatible siblings. The clinical characteristics of chronic cutaneous GVHD occurring in eight of these patients are summarized. There were some differences from previous reports in the USA and Europe. The incidence (8/29: 28%) of skin lesions in chronic GVHD was low in contrast to the previously reported high incidence (79 90%). Cutaneous manifestations in six out of eight patients with chronic GVHD tended to be mild, and lichen-planus-like eruptions in the skin and scleroderma like lesions, which are well known as representative cutaneous manifestations of chronic GVHD, were rare. Furthermore, our statistical analysis indicated that there was no relationship between pretransplant total body irradiation and GVHD prophylaxis or acute GVHD and the onset of chronic cutaneous GVHD. The present study suggests that the differences from previous reports in the USA and Europe concerning chronic cutaneous GVHD may be attributable to differing genetic backgrounds in Japanese and western populations. PMID- 1422489 TI - Urate metabolism during bone marrow transplantation. AB - We studied urate metabolism in 36 patients undergoing both allogeneic and autologous bone marrow transplantation (BMT) without allopurinol. Most patients had low tumour burdens. Three different preparative regimens were used; busulphan/cyclophosphamide (BUCY); BCNU, etoposide, ara-C and melphalan (BEAM) and cyclophosphamide/total body irradiation (CY/TBI). Urate excretion rose during each of the regimens but the pattern of excretion varied with each regimen. Urate excretion remained elevated 72 h after completion of BEAM and BUCY, possibly reflecting the prolonged action of some of the agents used, e.g. melphalan, busulphan and etoposide. Urinary urate concentrations were unchanged compared with pre-chemotherapy levels reflecting the adequacy of the hydration protocol. No significant rise in creatinine was seen and no cases of tumour lysis syndrome occurred. Serum uric acid levels were a poor reflection of urate production, falling in most patients, and are an unreliable end-point for decisions regarding prophylaxis. BMT can be safely undertaken in patients with low tumour loads without allopurinol if an adequate urine volume is maintained. In this series, high levels of urate excretion often persisted for 72 h after the completion of conditioning and adequate hydration should be ensured during this period. PMID- 1422490 TI - Clonal imbalances of serum immunoglobulins after allogeneic bone marrow transplantation: an analysis by high-resolution two-dimensional gel electrophoresis. AB - The clonality pattern of immunoglobulins (Igs) produced after allogeneic bone marrow transplantation (BMT) was studied by high-resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of serum samples and purified Igs. With this technique, the light (L) chain of a monoclonal Ig usually appears as a single spot. Thus, the degree of clonal diversity of the functional B cells can be appreciated by the electrophoretic pattern of the serum L chains. Furthermore, 2D-PAGE allows a semi-quantitative determination of prominent Ig clones according to the size of L chain spots. We found that serum electrophoretograms of 8/19 patients after BMT (5-9 months) revealed L chain patterns which were similar to those of normal polyclonal Igs, that is, less than five distinguishable small spots among a cloud-like indiscrete L chain spots region ('polyclonal' pattern). A spectrum of clonal abnormalities was observed on the electrophoretograms of 11/19 patients: in five patients, multiple small L chain spots (corresponding to Ig concentrations between 0.2 and 2 g/l) were detected ('oligoclonal' pattern), whereas in six others, 'typical' monoclonal Igs (Ig concentrations > 2 g/l) were observed with (3/19 patients) or without (3/19 patients) multiple small clonal components. Sequential analysis of serum obtained from patients at different times after BMT revealed that imbalanced clonal reconstitution was transient and evolved towards apparently normal polyclonal Ig production. Our observations show that the development of clonal 'gammopathies' after BMT is a frequent, but not obligatory phenomenon. It may reflect a transient restriction of the B cell repertoire either through a limited outgrowth of precursor cells or through selective antigenic pressures. PMID- 1422491 TI - High-dose methylprednisolone therapy for acute graft-versus-host disease associated with matched unrelated donor bone marrow transplantation. AB - Acute graft-versus-host disease (aGVHD) is a major barrier to successful bone marrow transplantation (BMT) with matched unrelated donors. Eight of eight recipients of matched unrelated donor BMT developed aGVHD. We used a regimen of high-dose methylprednisolone (5 mg/kg/day for 4 days with responders continuing on treatment, and dose escalation to 10 mg/kg/day for non-responders) as initial therapy of aGVHD. One patient died on the second day of steroid administration. Each of the seven remaining patients responded to methylprednisolone, five at the 5 mg/kg/day dose and two at the 10 mg/kg/day dose. Three of five patients developed flare of aGVHD during reduction of the corticosteroid dosage and died with aGVHD and infection. Two patients have undergone reduction of methylprednisolone at a modified rate without a flare. Infectious complications during methylprednisolone treatment were very common and contributed to the death of the three patients with flare of aGVHD. Four patients in whom aGVHD was in remission survived serious systemic infections. High-dose methylprednisolone is effective initial therapy for aGVHD associated with matched unrelated BMT, but is associated with a high risk of serious infections. PMID- 1422492 TI - Evaluation of pulmonary complications after bone marrow transplantation: the role of pretransplant pulmonary function tests. AB - To determine whether an association exists between abnormal pulmonary function tests (PFT) before bone marrow transplantation (BMT) and the rate of pulmonary complications after BMT, we retrospectively reviewed all transplants performed in our center between March 1984 and December 1990. A total of 163 patients, 15 years of age and older, with a hematologic malignancy or a solid tumor were treated with intensive therapy and autologous (118) or allogeneic (55) BMT. Sixty patients (37%) developed a pulmonary complication which contributed to patient death in 29 transplants (18%). Patients with pulmonary metastases, prior thoracotomy, or prior radiation to the chest had a higher frequency of abnormal PFT. By univariate analysis, patients with abnormal FVC, FEV1, or TLC before BMT had a significantly increased rate of pulmonary complications (p < 0.005). By multivariate analysis, the rate of pulmonary complications was significantly associated (p = 0.004) with abnormal FEV1 only: in the first 2 months after transplantation the rate was 65% in patients with FEV1 < 70% in contrast to 34% in patients with FEV1 > or = 70% (risk ratio = 1.9). There was no association, however, between abnormal pretransplant PFT and fatal pulmonary complications. We conclude that patients with pretransplant ventilatory defects have a higher risk of pulmonary complications after BMT, but the incidence of fatal complications was not significantly increased, although we cannot exclude a diminished study power due to the sample size. We believe that patients with abnormal PFT should not be excluded from transplantation if the anticipated anti-tumor effect is estimated to be substantial, but additional preventive measures may be necessary. PMID- 1422493 TI - Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients. AB - Ursodiol is a hydrophilic, non-hepatotoxic bile salt indicated for the medical treatment of cholesterol gallstones. This pilot study explored the use of prophylactic ursodiol in an attempt to decrease the incidence and severity of veno-occlusive disease (VOD) of the liver following allogeneic bone marrow transplantation (BMT). Between February 1991 and January 1992, 22 consecutive patients undergoing BMT for hematologic malignancies received the BU(4)/CY(2) preparative regimen and CSA/MTX for GVHD prophylaxis. Ursodiol, 600-900 mg daily by mouth was begun at least 1 day prior to beginning the preparative regimen. Results for this pilot group were compared to a control group of 28 consecutive patients transplanted between June 1989 and January 1991 with the same regimen without ursodiol. There were no significant differences in disease or clinical status between the groups pretransplant. However, mean baseline AST levels were significantly higher in the ursodiol group, 28.0 U/l vs 18.1 U/l in the control group (p = 0.001). The median maximum bilirubin observed post-transplant was 2.35 mg/dl (range 0.9-45) in the ursodiol group, and 5.05 mg/dl (range 0.7-29.4) in controls. The incidence of VOD was 2/22 (9.1%) in the ursodiol group and 18/28 (64.3%) in controls (p = 0.0001). Death due to VOD occurred in 1/22 patients (4.5%) in the ursodiol group and in 6/28 (21.4%) controls (p = 0.12). Our data suggest that ursodiol may decrease the incidence of VOD in allogeneic BMT patients. PMID- 1422494 TI - Congenital sideroblastic anemia successfully treated by allogeneic bone marrow transplantation. AB - Allogeneic bone marrow transplantation (BMT) was carried out on a 34-month-old boy with congenital sideroblastic anemia. The patient had been red blood cell transfusion dependent since the age of 7 weeks. He did not respond to therapy with pyridoxine and developed secondary progressive hemosiderosis. The preparatory regimen consisted of busulfan (3.5 mg/kg for 4 days) and cyclophosphamide (50 mg/kg for 4 days). Full engraftment of donor bone marrow was achieved and effective hemopoiesis is still maintained 3 years after BMT. PMID- 1422495 TI - Bullous pemphigoid associated with acute graft-versus-host disease after allogeneic bone marrow transplantation. AB - A 47-year-old patient was treated with allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukaemia in blast crisis. Three months after the procedure he developed bullous pemphigoid (BP) and symptoms suggestive of BP oesophageal involvement, associated with skin and liver acute graft-versus-host disease. The occurrence of BP is exceptional after BMT. PMID- 1422496 TI - Successful T cell-depleted allogeneic bone marrow transplantation in a child with recurrent multiple extramedullary plasmacytomas. AB - Multiple plasmacytomas with IgA paraproteinemia, a low grade lymphoid neoplasm of differentiated B cells rarely seen in the young, were encountered in a 10-year old child. T cell-depleted allogeneic bone marrow transplantation (BMT) was performed because of progressive disease despite chemotherapy. Donor T cells were infused after transplantation in gradually increasing numbers to achieve a graft versus-tumor effect. Complete eradication of all tumor masses was achieved following BMT with normalization of serum immunoglobulin levels. The patient remains in complete remission 4 years after BMT. Allogeneic BMT should be considered early in the course of low-grade lymphoid malignancy in the younger age group. PMID- 1422497 TI - Encephalopathy and seizures induced by intravesical alum irrigations. AB - Hemorrhagic cystitis is a significant toxic effect of cyclophosphamide therapy. Continuous bladder irrigation of a 1% alum solution is a simple and generally safe method of chemical cautery to treat the bleeding urothelium. We report four cases of encephalopathy coincident with elevated aluminum levels as well as one patient who developed seizures while receiving continuous bladder irrigations with alum. All patients had significant renal insufficiency. We recommend the cautious use of alum irrigation in patients with renal impairment and monitoring of serum aluminum levels to prevent excessive accumulation and toxicity. PMID- 1422498 TI - Relapse of acute leukemia presenting as acute cholecystitis following bone marrow transplantation. AB - Though included in the differential diagnosis of jaundice and abdominal pain, acute acalculous cholecystitis is an uncommon hepatobiliary complication of bone marrow transplantation. Leukemic infiltration of the gallbladder presenting as acute cholecystitis is rare. We describe two cases of acute cholecystitis following marrow transplantation that represented an unexpected relapse with leukemic infiltration of the gallbladder wall. PMID- 1422499 TI - Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression. AB - Two patients with hematologic relapse of chronic myelogenous leukemia (CML) following allogeneic BMT were treated by abrupt discontinuation of cyclosporine. Both patients rapidly attained complete hematologic and cytogenetic remission and remain free of disease with long follow-up. In the first patient, disappearance of CML was associated with the development of graft-versus-host disease (GVHD). In the second patient GVHD did not develop until after clearing of disease had been documented by cytogenetic analysis. Laboratory studies in the second patient disclosed the presence of lytic activity against both K562 and autologous CML cells that enhanced with IL2. Correlation with serial immunophenotyping data from this patient suggests that the effector for this graft-versus-leukemia (GVL) reaction could have been a T lymphocyte. Abrupt discontinuation of post transplant immunosuppression with cyclosporine may represent a therapeutic approach to CML which has recurred following BMT. Moreover, investigation of this clinical phenomenon in subsequent cases may permit direct study of the cellular mechanisms involved in the GVL effect. PMID- 1422500 TI - Development of hyperthyroidism in donor and recipient after allogeneic bone marrow transplantation. PMID- 1422501 TI - Syndrome--a changing concept. AB - Syndrome is one of the oldest terms in the medical vocabulary. Traditionally, the term has been used mainly as a designation for complex medical entities, such as multiple abnormalities, that are characterized by clusters of concurring symptoms, usually three or more. During the mid-twentieth century, the meaning and the use of the term were altered. First to take place was an attempt to eliminate physicians' names from syndrome nomenclature, resulting in a significant increase in the use of descriptive designations in proportion to eponyms. But the trend was counterbalanced by the creation of new classes of eponyms. Eponymous syndrome nomenclature now includes the names of literary characters, patients' surnames, subjects of famous paintings, famous persons, geographic locations, institutions, biblical figures, and mythological characters. This was followed by a relaxation in the scope of the definition of syndrome, wherein the term could also be used as a modifier indicating a special (sometimes unspecified) complexity of an already named pathological condition. Eventually syndrome changed from its original use as an exclusively medical term and came to mean anything unusual, abnormal, bizarre, or humorous, whether medical, social, behavioral, or cultural. This unrestrained use of the term is the principal cause of an enormous volume of the sometimes irrelevant syndrome literature cluttering databases in the MEDLARS system and of the deterioration of "SYNDROME" as a specific MeSH term and a useful search parameter. PMID- 1422502 TI - The characteristics of medical retraction notices. AB - During the past twenty years, more than ninety retraction notices have been published in biomedical journals. These retractions constitute a unique body of literature that biomedical researchers, bibliographers, and librarians must monitor to reduce scientific use of retracted, invalid papers. An analysis of medical retraction notices shows that very few are prominent in style, format, or placement, in spite of authoritative publication standards formulated by the International Council of Medical Journal Editors. Although researchers are ultimately responsible for the validity of the information they cite in their own publications, biomedical librarians are in a unique position to educate their patrons regarding retracted papers. PMID- 1422503 TI - Using BITNET to access the National Library of Medicine databases. AB - An ongoing developmental project is described that uses the National Library of Medicine (NLM) GRATEFUL MED software on the BITNET network to access the NLM databases. The objective of the project is to improve biomedical communication capabilities to support health professionals in countries where international telecommunication services are limited. After a successful demonstration of the concept, the system was assembled and tested by the University of Chile and NLM. The full impact of this project will be measured at a later time. This paper describes the concept and testing of the system in Latin American countries. PMID- 1422504 TI - Research in health sciences library and information science: a quantitative analysis. AB - A content analysis of research articles published between 1966 and 1990 in the Bulletin of the Medical Library Association was undertaken. Four specific questions were addressed: What subjects are of interest to health sciences librarians? Who is conducting this research? How do health sciences librarians conduct their research? Do health sciences librarians obtain funding for their research activities? Bibliometric characteristics of the research articles are described and compared to characteristics of research in library and information science as a whole in terms of subject and methodology. General findings were that most research in health sciences librarianship is conducted by librarians affiliated with academic health sciences libraries (51.8%); most deals with an applied (45.7%) or a theoretical (29.2%) topic; survey (41.0%) or observational (20.7%) research methodologies are used; descriptive quantitative analytical techniques are used (83.5%); and over 25% of research is funded. The average number of authors was 1.85, average article length was 7.25 pages, and average number of citations per article was 9.23. These findings are consistent with those reported in the general library and information science literature for the most part, although specific differences do exist in methodological and analytical areas. PMID- 1422505 TI - Total quality management (TQM) in a hospital library: identifying service benchmarks. AB - Hospitals are turning to total quality management (TQM) to lower costs of providing care. A hospital library in a TQM environment needs to embrace corporate goals while maintaining its accountability as a contributor to quality patient care. Alliant Health System (AHS) Library at Norton Hospital and Kosair Children's Hospital in Louisville, Kentucky, conducted a study to establish TQM benchmarks and to examine the significance of its role in clinical care. Using a methodology designed to allow both library user and nonuser to respond, 2,091 surveys were distributed to physicians and nursing and allied health personnel. Areas surveyed included frequency of library use, impact of information received on clinical judgments, cognitive value of the information, and satisfaction with library products and services. Results confirm that the library has a substantial clinical role. Eighty-eight percent of reporting physicians agreed that information from the library contributed to higher quality care. Nursing and allied health were less convinced of the importance of the library's clinical role. Sixty-nine percent of nursing personnel and 58% of allied health personnel agreed that the library contributed to higher quality care. Nursing and allied health personnel also used the library less frequently than physicians. With these results as benchmarks, improving the clinical role of the library will take commitment to the TQM process and a willingness to change. PMID- 1422506 TI - Factors influencing research productivity among health sciences librarians. AB - Secondary analysis was performed of data collected in 1989 from a random sample of members of the Medical Library Association. Results show that about half the sample had at least one publication; academic health sciences librarians were much more likely than hospital librarians to have published. Almost half the sample had taken formal courses in research, but only a small percentage had taken continuing education (CE) courses in research. Institutional support services for research were most available in academic settings. The combination of institutional support, CE training, and research courses explained 31.1% of the variation in research productivity among academic librarians; these factors were less important in hospitals and other institutional settings. The authors suggest that health sciences librarians working outside academia should seek support for research from sources outside the employing institution. PMID- 1422507 TI - The landmark citation method: analysis of a citation pattern as a collection assessment method. AB - The landmark citation method is a new collection assessment method based on the citation record of a single landmark article. This citation record is developed by identifying sources which cite the landmark article. A bibliography, extracted from the citation record, is then used to complete an assessment of the collection. This method was developed and used to assess the biotechnology collection of the National Library of Medicine. The information gained from this study, in addition to demonstrating the technique, also provided insight into the evolution of the biotechnology literature. PMID- 1422508 TI - Computer database searching and professional malpractice: who cares? PMID- 1422510 TI - Physician retraining, lifelong learning, and the library. PMID- 1422509 TI - The Beijing Medical Library. PMID- 1422511 TI - Dial-in access to CD-ROM databases: beyond the local area network. AB - Although it has meant additional work, CDLink has enhanced the productivity and effectiveness of the library's public services program. CDLink enables the library to offer dial-in access to databases, either in CD-ROM or other MS-DOS formats. The VAX MS-DOS connection is a cost-effective way to combine the benefits of remote access and multiple simultaneous use. From the user's perspective, CDLink provides free, twenty-four-hour remote access to databases in a friendly, menu-driven environment. For the library staff, the CDLink service represents the achievement of a long-awaited goal. PMID- 1422512 TI - A decade of AIDS literature. AB - From 1983 through mid-1991, more than 200,000 MEDLINE entries were AIDS-related. Close to 60% of the journals indexed in MEDLINE published at least one article on AIDS during the past ten years. As reflected by a subset of 29,077 MEDLINE records, the literature of AIDS has grown to encompass 29 languages and 65 countries. A bibliometric study of the medical literature helps to demonstrate the progression of AIDS as a world health problem and the concomitant expansion of the research effort underway to control it. PMID- 1422513 TI - The nature of PDQ. PMID- 1422514 TI - In support of research. PMID- 1422515 TI - Salaries and professional authority. PMID- 1422516 TI - [Academic elegy of Professor Jean-Jules Pasteels, titulary member]. PMID- 1422517 TI - [Academic elegy for Professor Carl Stainier; titular member and former president]. PMID- 1422518 TI - [Control of renal tubular regeneration]. AB - Tubular necrosis induced by various drugs (aminoglycosides, platinum-based anticancer agents) elicits a process of renal tissue repair which involves an increase of cell turnover. The proliferative response remains commensurate with the degree of tubular injury and occurs primarily in the area of tubular epithelium which has suffered injury. After acute renal necrosis, tubular regeneration is associated with a transient dedifferentiation of epithelial cells. This tissue reaction is controlled and leads in most cases to a complete reepithelialization of injured tubules and consequently to a full restoration of normal kidney functions. Recent experimental evidences suggest that EGF (Epidermal growth factor) plays a prominent role in the control of this repair process. By immunocytochemical and biochemical methods we have observed in regenerating kidneys a diminution of the membrane-bound precursor of EGF (prepro EGF) in distal tubules. Concomitantly, by electron microscopy, EGF immunoreactivity is detected on basolateral membranes of proximal tubules. These experimental data suggest that EGF precursor might be converted into a low molecular weight diffusible factor. The latter is able to interact with the receptors localized on the basolateral membranes of proximal tubules and to induce the tissue repair process. PMID- 1422519 TI - [Postoperative irradiation in pulmonary cancer?]. AB - Postoperative radiation remains a controversial issue in the management of lung cancer. Despite a better local control, a major concern is always the possible late lung effects induced by high doses of radiation required to achieve this benefit. In our works, we have been able to show that with an adequate technique and the use of CT-scan for treatment planning, such high doses can safely be delivered. Furthermore, several prognostic factors were identified including the degree of mediastinal lymph node involvement. PMID- 1422520 TI - The perversion of mothering: Munchausen syndrome by proxy. AB - Munchausen syndrome by proxy, in which a seemingly caring and concerned mother is simultaneously harming her child, can best be understood in terms of the mother's need for a relationship with a physician that is rooted in a profound sense of early abandonment. This understanding broadens the definition of perversions. The infant in this sadomasochistic interaction is dehumanized and is used as a fetishistic object to control the relationship. The author's literature review and case report provide the basis for his exploration of the historical, cultural, and psychological factors that both contribute to the development of the syndrome and conspire to deny its reality. PMID- 1422521 TI - Perceptions of family functioning and the occurrence of childhood sexual abuse. AB - The wide variety of sequelae attributed to childhood sexual abuse has led some authors to posit that it is the complex interaction between the object-relational developmental world of the child and the event and nature of the abuse that determines the enduring effects of the abusive experience. The authors addressed this hypothesis by examining the correlation between the occurrence of childhood sexual abuse and subjects' perceptions of the nature of their childhood family. Results revealed significant differences in the subjects' recollections of family functioning based on abuse status. Abused subjects recalled families that were isolative, rigidly ruled in an authoritarian style, and unable to foster the development of autonomy in family members. The authors discuss the study results in light of the interactions between memories of the childhood family and the experience of sexual abuse. PMID- 1422522 TI - Toward an experiential psychoanalytic approach to the Rorschach. AB - With a conceptual approach to the Rorschach, there is a strong tie between this test and a theory of personality that lies outside the test itself. Shifts in that personality theory can provide new concepts and formulations for understanding Rorschach data. Such shifts can also promote new and different ways of conceptualizing and using the test. The author contends that changes in psychoanalytic theory are currently facilitating a more experiential view of the Rorschach. He reviews the relationship between personality theory and Rorschach testing, discusses changes in psychoanalytic theory that are leading to a more experiential Rorschach psychology, and describes the meaning of an experiential approach to the Rorschach. PMID- 1422523 TI - Specialized extended hospital treatment for borderline patients. AB - The intensive psychoanalytically oriented hospital treatment described by the authors was developed specifically for borderline patients. This unique treatment, an integrated multimodal approach, is based on the theory that the disturbed behaviors and relationships of borderline patients are manifestations of intrapsychic impairment. The authors use a detailed case report to illustrate how the theory is transformed into technical precepts and applied to all aspects of the treatment. PMID- 1422524 TI - Distinguishing features of pseudocomplex partial seizures. AB - The authors identify common features in the clinical presentations of three patients whose pseudoseizures mimicked complex partial seizures. All three had suffered the recent traumatic loss of a significant love object, and all manifested unconscious feelings of guilt and the use of defense mechanisms of denial, dissociation, introjection, identification, and symbolization. The authors explore the diagnostic, treatment, and etiological implications of these findings. PMID- 1422525 TI - A psychodynamic approach to the master treatment plan. AB - Formulating master treatment plans for the hospital treatment of psychiatric patients is especially challenging to psychodynamically oriented clinicians unaccustomed to reducing complex intrapsychic and interpersonal phenomena to specific observable behaviors. In collaboration with a wide cross section of hospital staff members, the authors developed a conceptual framework for treatment plans compatible with psychodynamic thinking. They describe the treatment evaluation research from which the format of the treatment plan evolved, as well as the guide they developed to facilitate its implementation . PMID- 1422526 TI - The influence of religion on sexuality: implications for sex therapy. AB - Religious beliefs are among the many factors that determine whether sexually dysfunctional persons will seek out a sex therapist. These beliefs may also generate resistance to therapy or influence patients to drop out of treatment before it is complete. Therapists who are sensitive to patients' religious beliefs enhance the likelihood of a successful treatment process. The authors present six case examples from their practice in which religious beliefs played an important role. They urge sex therapists to become more aware of the religious dynamic and to help address the paucity of clinical case material in the literature. PMID- 1422527 TI - The grafting of plastic surgery. PMID- 1422528 TI - Is audit all hype? PMID- 1422529 TI - Software packages for audit. PMID- 1422530 TI - Radiological assessment of varicose veins. AB - Most patients with straightforward varicose veins only require a careful clinical examination combined with Doppler ultrasound scanning. When varicose veins are secondary to past deep venous thrombosis, recur after treatment or are associated with congenital anomalies, radiology is useful for diagnosis and management. PMID- 1422531 TI - Psychotherapy of schizophrenia. AB - Recent developments in the psychotherapy of schizophrenia have integrated educational methods, skills training, family-based stress management and specific cognitive-behavioural strategies with optimal pharmacotherapy. These approaches have demonstrated considerable promise in alleviating the impairments, disabilities and handicaps associated with schizophrenia. PMID- 1422532 TI - Clinical applications of flow cytometry. AB - Flow cytometers allow the rapid, sensitive and quantitative measurement of cells, cell surface markers and cell nuclear components for research and clinical laboratory use. They are producing new insights in many branches of clinical science. PMID- 1422533 TI - Breast cancer screening. PMID- 1422534 TI - Towards good audit. AB - All doctors are enjoined to audit, yet there is concern that many audits do not improve patient care. Despite the profusion of audit methods, good audits have many features in common. This paper identifies these essential features, facilitating the appraisal of proposed or completed studies. PMID- 1422535 TI - Cyclical Cushing's syndrome. PMID- 1422536 TI - Guide to postgraduate exams: Royal College exams. AB - Postgraduate exams are important milestones (or barriers) in specialist careers. However, there are several peculiar features in the Royal Colleges' exams, and considerable differences between them. This is the first of three articles aimed at helping candidates make appropriate preparations. PMID- 1422537 TI - Experts differ over diagnostic criteria for Munchausen syndrome by proxy. PMID- 1422538 TI - Optimistic response to NCEPOD--with provisos. PMID- 1422539 TI - Who benefits from lipid-screening programmes? PMID- 1422540 TI - Women in medicine. PMID- 1422541 TI - Application of urodynamics to incontinence. PMID- 1422542 TI - Cardiac rehabilitation: does it do any good? PMID- 1422543 TI - Sarcoidosis. AB - Sarcoidosis is a multisystem disorder of unknown cause characterized by non caseating granuloma formation and evidence of enhanced cellular immune response at the site of involvement. Although the majority of patients have a self limiting illness, a significant proportion develop severe chronic disability. PMID- 1422544 TI - Exercise: the best therapy for intermittent claudication? AB - The prophylactic value of physical activity for arteriosclerotic diseases is generally accepted. Regular exercise is also the most effective therapy for intermittent claudication although drug treatment is more popular in general practice. Recent findings show that exercise and drug treatments complement each other. PMID- 1422545 TI - Surgical treatment of urinary stress incontinence. AB - This article reviews traditional vaginal and suprapubic procedures as well as more recent advances such as urethral bulking agents and artificial sphincters. It illustrates how the chosen operation must be tailored to the individual patient and how the surgeon treating urinary incontinence requires a variety of procedures in his repertoire. PMID- 1422546 TI - Transport of the critically ill child. AB - The principles of stabilization before, and monitoring during, transportation are well established in adult intensive care practice but less so in paediatrics. The speed with which critically ill children deteriorate and the aggressiveness of treatment needed are often underestimated. A dedicated, fully funded and staffed transport service for each paediatric referral centre in the UK is urgently required. PMID- 1422547 TI - Causes and management of dysphasia. AB - Dysphasia comprises a wide-ranging complex of linguistic impairments. Comprehensive and individual description of the verbal and non-verbal aspects is required for the tailoring of an approach to therapy and management. PMID- 1422548 TI - Problem-based learning. AB - Problem-based learning is now a well-established approach to the design and implementation of undergraduate, postgraduate and continuing medical education. This article describes how it functions and examines how it contributes to more enjoyable and effective professional development. PMID- 1422550 TI - NHS to avoid the Oregon trail. PMID- 1422549 TI - Anaesthesia for the obstetric trainee. AB - The practice of obstetric anaesthesia and analgesia ranges from the sublime to the ridiculous. Try to contrast the satisfaction of having produced an effective epidural block with the agonizing personal loneliness of failing to intubate at emergency caesarean section, and you may begin to understand our position: we either love it or loathe it. PMID- 1422551 TI - Can adenosine help dispel misconceptions? PMID- 1422552 TI - Indications for hyperbaric oxygen therapy. PMID- 1422554 TI - Teaching the public cardiopulmonary resuscitation. PMID- 1422553 TI - Rest or exercise in inflammatory arthritis? PMID- 1422555 TI - Vitamins and mental health. PMID- 1422556 TI - Screening for early ovarian cancer. AB - Transvaginal ultrasound scanning with colour Doppler imaging can be used to detect early ovarian cancer. About one in three women with a family history of the disease and a positive screening result (i.e. a persistent intraovarian mass with a characteristic blood supply) will have histological signs of primary cancer. A randomized controlled clinical trial should be undertaken to assess whether screening and immediate treatment of women from the general population will improve survival rates from the disease. PMID- 1422558 TI - Sex therapy: the successes, the failures, the future. AB - Sexual dissatisfaction or dysfunction occurs in one fifth to one third of the adult population. Although great advances have been made in the pharmacological treatment of impotence, psychological and relationship therapy remain the mainstay of the treatment of sexual problems within relationships. PMID- 1422557 TI - Laparoscopic cholecystectomy. AB - The technique of laparoscopic cholecystectomy is probably the most significant major surgical advance of the last decade. It allows shorter hospitalization, rapid recovery and early return to work. Significant financial savings may be achieved over current conventional treatment. In this article the procedure is reviewed and its advantages and drawbacks are discussed. PMID- 1422560 TI - Bronchiolitis obliterans organizing pneumonia. AB - Bronchiolitis obliterans organizing pneumonia (BOOP) is a rare cause of pulmonary infiltration and breathlessness which is usually associated with systemic and constitutional ill health. Its aetiology is unclear. The importance of its recognition lies in the characteristic response of the condition to treatment with high-dose corticosteroids. PMID- 1422559 TI - Cyclosporin-induced nephrotoxicity and hypertension. AB - The use of cyclosporin in therapeutics is increasing. Unfortunately, cyclosporin has important detrimental effects on kidney function and blood pressure. Based on the pathogenesis of these side effects, different drug groups have been studied, but with variable success. PMID- 1422561 TI - Infections and intravascular devices. AB - Complications associated with intravascular devices include infections mainly caused by Staphylococcus epidermis and S. aureus. The reported incidence of these infections varies. Several factors influence the propensity for catheter infections. We recommend strategies for the prevention and treatment of catheter related sepsis. PMID- 1422562 TI - Antiphospholipid syndrome in pregnancy. PMID- 1422563 TI - Blunkett's tack hits a rich seam. PMID- 1422564 TI - Paraphrenia diagnosis. PMID- 1422565 TI - Testicular tumour. PMID- 1422566 TI - Cholesterol testing. PMID- 1422567 TI - Alteration of the L-type calcium current in guinea-pig single ventricular myocytes by heptaminol hydrochloride. AB - 1. The effects of heptaminol on calcium current amplitude and characteristics were studied in single ventricular myocytes of guinea-pig by use of the whole cell configuration of the patch clamp technique. 2. A concentration-dependent decrease in ICa amplitude was observed. At heptaminol concentration as low as 10( 6) M, this effect was observed in only two cells (n = 6). At 10(-5) M the reduction of ICa was of 30 +/- 15% (n = 11). 3. The current recovery from inactivation at -40 mV holding potential (HP) seemed less sensitive to perfusion with heptaminol (greater than 10(-6) M). However, at -80 mV HP the overshoot of the recovery curve was decreased by heptaminol. 4. Both at -40 mV and -80 mV HP, heptaminol (10(-5) M) significantly increased the steady state inactivation of ICa. 5. As previously proposed by others to explain the effects of membrane active substances, the effects of heptaminol may result from alterations in cell membrane properties and possibly from an increase in intracellular free calcium ion concentration. PMID- 1422568 TI - Characterization of 8-OH-DPAT-induced hypothermia in mice as a 5-HT1A autoreceptor response and its evaluation as a model to selectively identify antidepressants. AB - 1. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) dose-dependently induced hypothermia in mice. 2. The 5-HT1A receptor partial agonists, buspirone, gepirone and ipsapirone, also dose-dependently induced hypothermia. 3. The 8-OH-DPAT temperature response was antagonized by the 5-HT1 receptor antagonists quipazine (2 mg kg-1, i.p.), (+/-)-propranolol (10 mg kg-1, i.p.). (+/-)-pindolol (5 mg kg 1, i.p.), spiroxatrine (0.5 mg kg-1, i.p.) and metitepine (0.05 mg kg-1, i.p.), but not by 5-HT2 (ketanserin) or 5-HT3 (MDL 72222, GR 38032F) receptor antagonists. 4. The response was also antagonized by the dopamine D2 receptor antagonists, haloperidol and BRL 34778. No other catecholamine or muscarinic receptors were involved in mediating the response. 5. Destruction of 5 hydroxytryptamine (5-HT)-containing neurones with the neurotoxin, 5,7 dihydroxytryptamine (75 micrograms, i.c.v.), abolished the response to 8-OH-DPAT indicating that the 5-HT1A receptors involved were located on 5-HT neurones. 6. Chronic antidepressant treatment down-regulated this 8-OH-DPAT response. In addition, chronic administration of anxiolytics and neuroleptics was also effective in this respect. Down-regulation was also observed following repeated administration of 8-OH-DPAT (0.5 mg kg-1, s.c.), (+/-)-pindolol (10 mg kg-1, i.p.) and ketanserin (0.5 mg kg-1, i.p.). 7. In conclusion, these data confirm that 8-OH-DPAT-induced hypothermia is mediated by 5-HT1A autoreceptors. They also indicate that the response involves D2 receptors.The present study also shows that a wide range of antidepressant drugs down-regulate this response although this property is not restricted to antidepressant treatments. Therefore, care should be exercised when interpreting data from this paradigm. PMID- 1422569 TI - Effects of cromakalim on the membrane potassium permeability of frog skeletal muscle in vitro. AB - 1. The effects of the potassium channel opener, cromakalim, and its active enantiomer, lemakalim, have been investigated in frog skeletal muscle. 2. Cromakalim (30-300 microM) increased 86Rb efflux from muscles loaded with the isotope, hyperpolarized the fibres and reduced membrane resistance. 3. These effects were inhibited by the sulphonylureas, glibenclamide and tolbutamide. The IC50 for glibenclamide inhibition of 86Rb efflux was ca. 8 nM. 4. Phentolamine (300 microM) (which blocks responses to cromakalim in smooth muscle and inhibits ATP-sensitive K+ channels in pancreatic beta-cells) had no effect on the reduction in membrane resistance caused by 100 microM lemakalim. 5. Diazoxide (600 microM) had no effect on 86Rb efflux. 6. The similarities of the K+ channel activated by cromakalim in frog skeletal muscle to the channel acted on in smooth muscle and to the ATP-sensitive K+ channel of beta-cells are discussed. PMID- 1422570 TI - Pharmacokinetic-EEG effect relationship of midazolam in aging BN/BiRij rats. AB - 1. The purpose of the present investigations was to determine the influence of increasing age on the pharmacokinetics and pharmacodynamics of midazolam in male BN/BiRij rats as an animal model of aging. 2. Midazolam was administered intravenously at a dose of 2.5 mg kg-1 and its pharmacokinetics were determined on the basis of plasma concentrations as measured by high performance liquid chromatography (h.p.l.c.). Pharmacodynamics were studied using the midazolam induced changes in the electro-encephalogram (EEG) as a measure of the pharmacological effect. Results were evaluated on the basis of simultaneous pharmacokinetic-pharmacodynamic modelling. In an attempt to differentiate between the effects of aging and of concurrent disease, an extensive clinical biochemical/pathological examination was conducted in individual rats by an independent pathologist. 3. The pharmacokinetics of midazolam were best characterized on the basis of a two exponential model. In the 4-month-old rats the values of the clearance, volume of distribution and elimination half-life were 104 +/- 13 ml min-1 kg-1 (mean +/- s.e. mean), 3.4 +/- 0.7 l kg-1 and 30 +/- 3 min, respectively. With increasing age, no changes in the pharmacokinetics of midazolam were observed. 4. The pharmacodynamics of midazolam were determined on the basis of the sigmoidal Emax model. In the 4-month-old rats the values of the parameters relative maximum effect, midazolam concentration at half maximum effect and Hill factor were 106 +/- 10%, 50 +/- 6 micrograms l-1 and 1.6 +/- 0.3, respectively. In the group as a whole no significant changes in the pharmacodynamic parameters of midazolam were observed.4. The pharmacodynamics of midazolam were determined on the basis of the sigmoidal Emax model. In the 4 month-old rats the values of the parameters relative maximum effect, midazolam concentration at half maximum effect and Hill factor were 106 +/- 10%, 50 +/-6 lg 1' and 1.6 +/- 0.3, respectively. In the group as a whole no significant changes in the pharmacodynamic parameters of midazolam were observed. However, when diseased animals were excluded from the evaluation, a tendency towards a decrease in the midazolam concentration at half maximum effect to 25 +/- 14 pg 1-1 was observed in the 36-month-old rats.5. These findings suggest, that increasing age is associated with a tendency towards an increased brain sensitivity to midazolam, which is reflected in a parallel shift of the concentration vs. EEG effect relationship towards lower concentrations. However, it appears that factors other than age also contribute to interindividual variability in pharmacodynamics, considering the substantial interindividual variability within certain age groups. PMID- 1422571 TI - Effects of inhibition of the L-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro. AB - 1. The present study was performed to investigate how blockade of the L arginine/nitric oxide (NO) pathway influences the function of the lower urinary tract in vivo, as studied by cystometry in conscious rats and in vitro, in isolated muscle preparations from the rat detrusor and urethra. 2. L-NG-nitro arginine methyl ester (L-NAME), 10 and 20 mg kg-1, administered intra-arterially, decreased micturition volume and bladder capacity, and increased spontaneous bladder contractions. D-NAME (20 mg kg-1) had no effect. No changes in the urodynamic parameters were recorded if L-NAME (20 mg kg-1) was administered in combination with L-arginine (200 mg kg-1). 3. Cystometries performed after intra arterial administration of sodium nitroprusside (SNP) (3 mg kg-1) and 3 morpholino-sydnonimin hydrochloride (SIN-1, 2 mg kg-1) showed a decrease in bladder capacity, micturition volume and threshold pressure. SIN-1, but not SNP, induced spontaneous bladder contractions. 4. Isolated precontracted urethral preparations responded to electrical stimulation with a frequency-dependent tetrodotoxin-sensitive relaxation. L-NAME (10(-4) M), but not D-NAME, reduced the maximal relaxation to 31 +/- 8% (n = 8) of the response prior to drug administration. The inhibition induced by L-NAME was completely reversed by L arginine (10(-3) M). SNP (10(-8)-10(-4) M), SIN-1 (10(-6)-3 x 10(-4) M) and NO (10(-5)-10(-3) M; present in acidified solution of NaNO2), caused relaxation (93 100%) of urethral preparations. L-NAME did not affect these relaxations.5. Detrusor strips contracted by carbachol or K' showed contractions in response to electrical stimulation, even when pretreated with a,p-methylene ATP and/or atropine. Small relaxations (14-41%) of detrusor strips were evoked by SNP (10-6 10-4M), SIN-1 (10-5-3 x 10-4M) and NO (10-5-10-3M). Electrically (20 Hz) induced contractions of the detrusor muscle were unaffected by addition of L-NAME (10 6_10-4 M) or L-arginine (10-3 M).6. The present results suggest that the L arginine/NO pathway is of functional importance for the bladder outlet region, but that its role in the detrusor is questionable. They also suggest that the site of action of L-NAME for inducing bladder hyperactivity in the rat is the outlet region rather than the detrusor muscle. PMID- 1422572 TI - Effect of nucleotides on the cytosolic free calcium activity and inositol phosphate formation in human glomerular epithelial cells. AB - 1. Glomerular epithelial cells (GEC) were cultured from human kidneys and immunologically characterized. 2. The effect of extracellular nucleotides on the cytosolic free calcium activity [Ca2+]i was investigated with the fura-2 microfluorescence method. Extracellular UTP, UDP, UMP, ATP, adenosine 5'-O-(3 thio)-trisphosphate (ATP-gamma-S), inosine-triphosphate (ITP), guanyltriphosphate (GTP), 2-methylthio-ATP, AMP, alpha,beta-methylene-ATP and adenosine led to a rapid, transient, concentration-dependent increase of [Ca2+]i, followed by a plateau above the baseline level. 3. In a calcium-free extracellular solution, the rapid increase of [Ca2+]i was still present, whereas the plateau level was abolished. 4. ATP and UTP (ED50 both: 10(-5) M) stimulated inositol trisphosphate (InsP3) formation in GEC. 5. The order of potency for the purine nucleotides in stimulating InsP3 formation was ATP = ATP-gamma-S greater than ADP greater than 2 methylthio-ATP greater than AMP = a,beta methylene-ATP = adenosine. 6. The increase of InsP3 induced by ATP (10(-5) M) could be inhibited by the P2 receptor blocker suramin (greater than 10(-4) M). Reactive blue 2 exhibited a weak stimulating effect on the InsP3 formation and only a weak inhibitory effect at a concentration of 10(-3) M was observed. 7. Protein kinase C activation by preincubation of GEC with phorbol 12-myristate 13-acetate (PMA, 100 ng ml-1, 15 min) abolished the effect of ATP (10(-5) M) on InsP3 formation. Downregulation of protein kinase C by long term incubation (18 h) with PMA had no significant effect on the phosphoinositol turnover induced by ATP.8. The results indicate that an increase of [Ca2+]i and inositol phosphate breakdown can be mediated via activation of a P2 receptor in human GEC. PMID- 1422573 TI - Elevation of cytosolic calcium by cholinoceptor agonists in SH-SY5Y human neuroblastoma cells: estimation of the contribution of voltage-dependent currents. AB - 1. Muscarinic but not nicotinic receptor stimulation in SH-SY5Y human neuroblastoma cells induces a concentration-dependent increase in [3H]-inositol phosphate formation and a biphasic increase in [Ca2+]i. The latter involves release from both an intracellular store and Ca2+ entry across the plasma membrane. Here we examine the possibility that this agonist-stimulated Ca2+ entry occurs indirectly, as a consequence of depolarization. 2. Electrophysiological characterization, by whole cell patch-clamp techniques revealed that SH-SY5Y cells possess a tetrodotoxin-sensitive inward sodium current, a dihydropyridine insensitive calcium current and an outward potassium current which was blocked by tetraethylammonium, 4-aminopyridine and intracellular caesium ions. The outward potassium current showed voltage-dependent activation and inactivation, similar to that seen for A-currents. 3. Application of nicotinic agonists evoked an inward current in cells voltage-clamped at negative holding potentials, but this current rectified, resulting in little or no outward current flow at positive potentials. The mean amplitude at a holding potential of -60 mV was -1.14 nA. Extrapolation of the current-voltage relation gave a reversal potential of +8 mV, indicative of a non-specific cationic permeability. 4. Application of muscarinic agonists had no detectable effect in most of the cells tested. However, in one third of cells studied, a small slowly activating inward current was observed. The mean amplitude of this current at a holding potential of -60 mV was -8.3 pA.5. This study confirms that SH-SY5Y cells possess voltage-dependent sodium, potassium and calcium currents. In addition, these cells are strongly depolarized by nicotinic agonists, which produce little change in [Ca2t]1. On the other hand, muscarinic agonists produce profound changes in [Ca2+1J with only a small inward current (depolarization). The contrasting effects of these two cholinoceptor agonists strongly implies that the Ca2+ entry after muscarinic receptor activation is not primarily due to activation of voltage-dependent calcium channels. PMID- 1422574 TI - In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non pregnant human myometrium. AB - 1. Prostaglandin F (PGF), PGD, PGI and thromboxane A2 (TXA2) receptors have been pharmacologically characterized on the non-pregnant human myometrium in vitro in accordance with the receptor classification proposed by Coleman et al. (1984). The tools for the classification include both natural prostanoids, synthetic, selective analogues and antagonists where available. 2. The potent excitatory actions of the natural FP-receptor prostanoid, PGF2 alpha, and the synthetic analogue, fluprostenol, indicate the presence of FP-receptors mediating contraction on the human myometrium. 3. PGD2 produced a biphasic response consisting of excitation followed by relaxation of spontaneous activity of the myometrium. The selective DP-receptor agonists, BW245C, produced purely inhibitory responses illustrating the presence of inhibitory DP-receptors in this tissue. The inhibitory responses of both PGD2 and BW245C were antagonized by the competitive DP-receptor antagonist, BWA 868C, providing conclusive evidence for the existence of DP-receptors. 4. PGI2 produced a biphasic response similar to PGD2. Iloprost, the EP1/IP-receptor agonist also produced a biphasic response, whilst the IP-receptor selective agonist, cicaprost, caused inhibition only, suggesting that inhibitory IP-receptors exist in the non-pregnant human myometrium. 5. The TXA2-mimetic, U46619, produced marked stimulation of the non pregnant human myometrium and was approximately equipotent to PGF2 alpha and fluprostenol in this effect. The actions of U46619 were competitively antagonized by the TP-receptor antagonist GR32191 showing that excitatory TP-receptors exist in this tissue.6. All prostanoids tested, both natural and synthetic, had activity on the non-pregnant human myometrium in vitro, supporting the existence of a heterogeneous population of prostanoid receptors in this tissue. If the results from the present study are combined with those previously reported for EP receptor agonists (Senior et al., 1991), it may be concluded that excitation may occur through FP-, TP-, EP3- and few EP,-receptors, whereas inhibition may occur through DP-, IP- and EP2-receptors. PMID- 1422575 TI - Evidence that 5-HT2 receptor activation decreases noradrenaline release in rat hippocampus in vivo. AB - 1. Recent electrophysiological studies have shown that 5-HT2/5-HT1C receptor agonists inhibit the electrical activity of noradrenergic neurones in the rat locus coeruleus. Here we examine the effect of various agonists and antagonists of 5-HT2/5-HT1C receptors on noradrenaline release in hippocampus of anaesthetized rats using microdialysis. 2. Subcutaneous administration of the 5 HT2/5-HT1C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI: 0.2 and 0.5 mg kg-1), caused a marked decrease (50% of pre-drug levels 60 min after injection) of noradrenaline in hippocampal dialysates which was long lasting (greater than 120 min). Noradrenaline output also decreased in response to administration of the structural analogue of DOI, 1-(2,5-dimethoxy-4 bromophenyl)-2-aminopropane (DOB: 1 mg kg-1, s.c.). 3. The effect of DOI on noradrenaline output was prevented by pretreatment with the 5-HT2/5-HT1C receptor antagonist, ritanserin (0.4 mg kg-1, s.c.). Spiperone (0.2 and 1 mg kg-1, s.c.), a 5-HT2/dopamine D2 receptor antagonist which has low affinity for 5-HT1C receptors, also antagonized the effect of DOI (0.5 mg kg-1, s.c.). Sulpiride (50 mg kg-1, s.c.), a dopamine D2 receptor antagonist did not alter the response to DOI (0.5 mg kg-1, s.c.). 4. Both the non-selective 5-HT receptor agonist, quipazine (1 mg kg-1, s.c.), and the 5-HT-releasing agent, p-chloroamphetamine (2 mg kg-1, s.c.), decreased noradrenaline release in hippocampus and these effects were antagonized by pretreatment with ritanserin (0.4 mg kg-1, s.c.).5. Our data suggest that in vivo, noradrenaline release in hippocampus is inhibited by 5-HT2 receptor activation. This effect is probably associated with a decrease in noradrenergic neuronal activity. PMID- 1422576 TI - Endogenous noradrenaline release from guinea-pig isolated trachea is inhibited by activation of M2 receptors. AB - Overflow of endogenous noradrenaline (NA) from guinea-pig isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses). The muscarinic receptor agonist oxotremorine inhibited the evoked overflow of NA in a concentration-dependent manner (EC50 84 nM). Methoctramine, pirenzepine and p fluoro-hexahydrosiladiphenidol (each 1 microM) shifted the concentration-response curves of oxotremorine to the right with apparent pA2 values of 7.60, 6.74 and 6.18, respectively. It is concluded that sympathetic nerve terminals in the guinea-pig trachea are endowed with inhibitory muscarinic M2 receptors. PMID- 1422577 TI - Nucleotide-dependent activation of KATP channels by diazoxide in CRI-G1 insulin secreting cells. AB - 1. Patch-clamp recording techniques were used, to examine the effects of diazoxide on KATP currents in CRI-G1 insulin-secreting cells in the presence of non-hydrolysable nucleotides. 2. In the presence of non- or slowly-hydrolyzed ATP analogues, bathing the intracellular aspect of cell-free membrane patches diazoxide inhibited KATP channel activity. 3. Under whole-cell recording conditions, with various non-hydrolysable nucleotides present intracellularly (after dialysis), diazoxide induced KATP current activation. The largest activation occurred with Mg-adenylyl-(beta, gamma-methylene) diphosphate (Mg-AMP PCP) present in the dialysing solution. This activation was diazoxide- and nucleotide-concentration-dependent. 4. In the absence of Mg2+, or in the presence of manganese (Mn2+) ions intracellularly, diazoxide did not induce KATP current activation, regardless of the species of nucleotide present in the pipette. 5. Intracellularly applied trypsin prevented the activation of KATP currents by diazoxide in the presence of Mg-AMP-PCP, an effect reversed by co-application of intracellular polymethylsulphonyl fluoride with the trypsin. 6. The application, by dialysis, of a CRI-G1 cell lysate, with negligible Mg-ATP, resulted in a substantial activation of the KATP current by diazoxide. 7. It is concluded that diazoxide can activate KATP channel currents by two separate pathways, one requiring a phosphorylation process, the other the presence of an intracellular protein coupled with a Mg-purine nucleotide. PMID- 1422578 TI - Evidence for a 5-HT1-like receptor mediating the amplifying action of 5-HT in the rabbit ear artery. AB - 1. The nature of the 5-hydroxytryptamine (5-HT) receptors which amplify the vasoconstrictor effect of methoxamine was examined in the rabbit isolated perfused ear artery with intact endothelium. Indices of amplification were leftward shifts of methoxamine dose-response (DR) curves produced by 5-HT (0.3 microM) (Method I), and the appearance of vasoconstrictor responses to 5-HT receptor agonists when methoxamine was present in a near-threshold concentration (Method II). 2. The amplifying effect of 5-HT (Method I) was unaffected by prazosin (0.08 microM), was partly depressed by 5-HT2-receptor antagonists in high concentrations (ketanserin 0.5 microM, LY53857, 1.0 microM), and was abolished by a non-selective antagonist of 5-HT1 and 5-HT2 receptors (methiothepin, 0.01 microM). 3. Amplifying potencies of agonists assessed by both Methods I and II were in the order 5-carbox-amidotryptamine (5-CT) greater than 5 HT greater than alpha-methyl 5-HT. The potency of sumatriptan (assessed by Method II only) was intermediate between those of 5-HT and alpha-methyl 5-HT. 4. Ketanserin and LY53857 inhibited the amplifying action of 5-CT to about the same extent as that of 5-HT. 5. The amplifying potencies of the agonists are in marked contrast to the reported contractile potencies in the rabbit aorta where the receptor is 5-HT2, but are almost identical with reported contractile potencies in the dog saphenous vein where the receptor is 5-HT1-like. 6. It is concluded that a 5-HT,-like receptor mediates the amplifying interaction between 5-HT and methoxamine in the rabbit ear artery which can be weakly blocked by ketanserin and LY53857.7. Since 5-CT was equipotent when applied separately to the intimal and adventitial surfaces of the artery, it is suggested that the 5-HT,-like receptors are distributed uniformly across the artery wall. PMID- 1422579 TI - Differential effects of endothelin-1 on the vasorelaxant properties of benzopyran and non-benzopyran potassium channel openers. AB - 1. The effects of endothelin-1 (ET-1) on the vasorelaxant properties of structurally different potassium channel openers (PCOs), BRL-38227, Ro 31-6930, SDZ PCO 400, EMD-52692, RP-49356 and pinacidil, were studied. 2. All PCOs evoked concentration-related relaxations of ET-1 (10 nM) or KCl (20 mM) contracted rat isolated aortic rings denuded of endothelium. BRL-38227, EMD 52692, SDZ PCO 400 and Ro 31-6930 were 11-42 times less potent in relaxing contractions to ET-1 than KCl. In contrast, this differential potency was not observed with RP-49356 or pinacidil. 3. BRL-38227 (0.06-3.0 microM), RP-49356 (0.3-3.0 microM) and pinacidil (0.3-3.0 microM) displaced KCl concentration-response curves to the right of controls, without modifying the maximum response. A subcontractile concentration of ET-1 (0.1 nM) prevented the inhibitory effects of low concentrations of BRL-38227 (0.06-0.1 microM) on KCl responses, but failed to modify those to RP-49356, pinacidil or high concentrations of BRL-38227 (0.3-3.0 microM). The inhibitory effects of BRL-38227 (0.1 microM) were also not changed by ET-3 (1.0 nM) or angiotensin II (0.1 nM). 4. In anaesthetized spontaneously hypertensive rats (SHR), cumulative bolus intravenous administrations of BRL 38227 (1-1000 micrograms kg-1, i.v.), Ro 31-6930 (1-1000 micrograms kg-1, i.v.), RP-49356 (10-1000 micrograms kg-1, i.v.) or nitrendipine (0.1-30 micrograms kg-1, i.v.) produced dose-dependent falls in diastolic blood pressure (DBP).ET-1 (i.v.) evoked a transient fall in DBP (1 pg kg- = 58 + 1 mmHg) which returnedto pre administration levels within 4 min.5. Pretreatment of anaesthetized SHR with ET-l (1 pg kg-', i.v.) significantly increased the ED,5 (dose to evoke a 15% fall in DBP) values for BRL-38227 and Ro 31-6930. However, ET-l failed to modify the ED,5 values for RP-49356 or nitrendipine. The ED50 values for all of the vasodilators studied were not modified by ET-1.6. Infusion of BRL-38227 (2 pgkg-'min-', i.v.) or RP-49356 (4 pgkg-'min', i.v.) to anaesthetized SHR evoked dose-related falls in DBP, with a corresponding increase in descending aortic blood flow (DABF) and a decrease in total lower body vascular resistance (TLBVR). Pretreatment with ET 1 (1 ptg kg-', i.v.) significantly attenuated the decreases in DBP and TLBVR observed with low doses of BRL-38227, but not RP-49356 or high doses of BRL 38227. In contrast, ET-3 (3 pig kg-, i.v.) failed to modify the effects of BRL 38227 on DBP or TLBVR.7. In conscious SHR, the fall in DBP to BRL-38227 (30 pgkg ', p.o.) was significantly reduced following ET-1 (1 pig kg-', i.a.) treatment. ET-1 (1 pg kg-', i.a.) pretreatment, however, failed to modify the decrease in DBP induced by an equieffective oral dose of RP-49356 (1001pgkg-1).8. In conclusion, ET-1 selectively attenuated the vasorelaxant effects of the potassium channel opener,BRL-38227 and other substituted benzopyrans. The results are compatible with the hypothesis that benzopyran PCOs and ET-1 have affinity for a site that does not recognise RP-49356 or pinacidil. Thus,ET-l can differentiate between structurally unrelated potassium channel openers. The cardiovascular effects of some, but not all, PCOs might be radically modified in the clinical setting by elevated endogenous levels of ET-1 associated with certain diseased states. PMID- 1422580 TI - Diazoxide-sensitivity of the adenosine 5'-triphosphate-dependent K+ channel in mouse pancreatic beta-cells. AB - 1. In mouse pancreatic beta-cells the regulation of the diazoxide-sensitivity of the adenosine 5'-triphosphate-dependent K+ channel (K-ATP-channel) was examined by use of the patch-clamp technique. 2. In intact beta-cells incubated at 37 degrees C in the presence of 3 mM D-glucose, diazoxide did not affect the single channel conductance but stimulated channel-opening activity. Diazoxide produced half-maximal effects at 82 microM and 13 fold activation at maximally effective concentrations (300-400 microM). The response to diazoxide (300 microM) was not completely suppressed by saturating tolbutamide concentrations (1 or 5 mM). 3. Inside-out patch-clamp experiments were carried out using an experimental protocol favouring phosphorylation of membrane proteins. Under these conditions diazoxide was ineffective in the absence of any nucleotides, weakly effective in the presence of MgATP (26 or 87 microM) and strongly effective in the presence of the Mg complexes of adenosine 5'-diphosphate, 2'-deoxyadenosine 5'-diphosphate or guanosine 5'-diphosphate (MgADP, MgdADP or MgGDP). 4. In inside-out patches exposed to nucleotide-free solutions, saturating concentrations of tolbutamide did not cause complete block of K-ATP-channels. When the channels were activated by MgdADP (48 microM), tolbutamide was even less effective. Sensitization of MgdADP-induced channel activation by diazoxide further weakened the effects of tolbutamide. 5. Diazoxide (50 or 300 microM) prevented the complete channel block induced by saturating tolbutamide concentrations in the presence of Mg2+ and ADP (1 mM). 6. In the presence of Mg2", the K-ATP-channel-blocking potency of cytosolic ATP decreased in the order inside-out> outside-out> whole-cell configuration of the patch-clamp technique.7. It is concluded that the K-ATP channel is controlled via four separate binding sites for inhibitory nucleotides (e.g. free ATP and ADP), stimulatory nucleotides (MgADP, MgdADP, MgGDP), sulphonylureas and diazoxide. Strong inhibition of the channel openings by sulphonylureas results from occupation of both sites for nucleotides. Diazoxide is only effective when the site for stimulatory nucleotides is occupied. PMID- 1422582 TI - Effects of lignocaine and quinidine on the persistent sodium current in rat ventricular myocytes. AB - 1. The effects of the Class 1 antiarrhythmic agents lignocaine and quinidine on action potentials, and on sodium currents and potassium currents activated by depolarization, were examined in rat isolated ventricular myocytes by the whole cell, tight seal recording technique. 2. Tetrodotoxin and lignocaine shortened, whereas quinidine prolonged, the duration of the plateau phase of action potentials. 3. At low concentrations, lignocaine and quinidine blocked a persistent sodium current that was resistant to inactivation but they had only a small effect on the transient sodium current. At higher concentrations, they also blocked the transient sodium current. 4. Quinidine, but not tetrodotoxin or lignocaine, depressed potassium currents activated by depolarization and this could account for the prolongation of the plateau phase caused by quinidine. 5. It is suggested that block of the persistent sodium current may be responsible, at least in part, for the antiarrhythmic action of lignocaine and quinidine. PMID- 1422581 TI - Inhibition by adrenergic neurone blocking agents of the relaxation induced by BRL 38227 in vascular, intestinal and uterine smooth muscle. AB - 1. The adrenergic neurone blocking agents, guanethidine and bretylium, have been tested for inhibitory activity against the actions of some relaxant drugs (BRL 38227, noradrenaline, sodium nitroprusside, theophylline) in vascular, intestinal and uterine smooth muscle. 2. In guinea-pig isolated taenia caeci pre-contracted with KCl (25 mM), BRL 38227 (0.1-10 microM) and noradrenaline (10 nM-100 microM) each caused concentration-dependent relaxation. Guanethidine and bretylium (50 microM) each antagonized the relaxation to BRL 38227 but not that to noradrenaline. At high concentration (500 microM), the adrenergic neurone blocking agents antagonized the action of BRL 38227 and, to some extent, that of noradrenaline. 3. In rat isolated aorta pre-contracted with noradrenaline (300 nM), BRL 38227 (0.0125-3.2 microM) and sodium nitroprusside (0.3-100 nM) each produced concentration-dependent smooth muscle relaxation. Guanethidine and bretylium (5-500 microM) each antagonized the action of BRL 38227 without antagonizing that of sodium nitroprusside. 4. Rats were pretreated with 17-beta oestradiol benzoate. Tension waves were then induced from segments of isolated, oestrogen-dominated uterus by transmural electrical stimulation or by oxytocin (0.2 nM). These tension waves were inhibited by BRL 38227 (0.025-3.2 microM) or theophylline (0.05-0.8 mM) in a concentration-dependent manner. Guanethidine (50 microM) antagonized the action of BRL 38227 in both the electrically- and oxytocin-driven tissues. In the electrically-driven tissues, guanethidine (50 microM) did not antagonize the inhibition to theophylline. 5. In KCl (25 mM) treated guinea-pig taenia caeci, guanethidine (50 microM) inhibited the efflux of 86Rb+ evoked by BRL 38227 (10 microM) but not that evoked by noradrenaline (10 microM). In contrast, apamin(100 nM) reduced the efflux of 86Rb+ which was promoted by noradrenaline, but did not affect efflux induced by BRL 38227.6. It is concluded that the adrenergic neurone blocking agents, guanethidine and bretylium (each at 50 microM), selectively inhibit the relaxant action of BRL 38227 in vascular, intestinal and uterine smooth muscle. If this inhibition reflects direct blockade of the K+-channel (KKCO) which is opened by BRL 38227, then the adrenergic neurone blocking agents act as inhibitors selective for KKCO as opposed to the small, apamin-sensitive (SKCa) and large (BKca) conductance, Ca2"-dependent K+-channels. PMID- 1422583 TI - A perfusion system for the long term study of macrophage activation. AB - 1. A closed system was developed for perfusing J774 macrophages in columns. The cells were perfused for up to 100 h, at which time they were still viable. 2. Stimulation with increasing concentrations (0.01-10 micrograms ml-1) of bacterial lipopolysaccharide (LPS) caused the cells to produce increasing amounts of nitrite in the perfusion medium. This production was time-dependent, reaching a plateau by 48-50 h. 3. The nitrite accumulation caused by 0.1 microgram ml-1 of LPS was augmented by priming the cells for 2 h with increasing amounts of interferon-gamma. The nitrite accumulation also reached a plateau under these conditions. 4. N-iminoethyl-L-ornithine (L-NIO, 30 microM) completely inhibited the accumulation of nitrite whereas dexamethasone (0.3 microM) caused 60-70% inhibition. 5. Perfusion of the cells without L-arginine prevented the nitrite accumulation. Replacement of this amino acid after 20 or 50 h of perfusion led to a rapid generation of nitrite, the levels of which continued to increase for the duration of the experiment. 6. Thus, the perfusion system can be used to study the kinetics of the activation of the NO synthase and most likely other parameters in J774 cells and probably other cells in culture. An observation already of interest is that the 'disappearance' of the NO synthase after its activation can be prevented or reduced by removal of L-arginine from the medium. PMID- 1422585 TI - Capsazepine reversal of the antinociceptive action of capsaicin in vivo. AB - 1. This study was designed to investigate the antinociceptive activity of capsaicin in acute and persistent nocifensor behavioural models and to determine whether this was mediated via a specific receptor interaction, by use of the antagonist, capsazepine. 2. Capsaicin administered systemically in low doses produced antinociception in the knee joint hyperalgesia, rat paw pressure, rat and mouse tail flick and mouse hot plate nocifensor models with similar efficacy in all tests. 3. The novel competitive capsaicin antagonist, capsazepine, prevented the capsaicin-induced antinociception when administered systemically in the range 50-100 mumol kg-1. 4. Capsazepine administered by itself had no antinociceptive actions. 5. These data describe a joint hyperalgesic model in the rat which does not rely on extreme nocifensor behavioural endpoints and it is suggested this is a useful model for investigating mechanisms in persistent pain. 6. This is the first demonstration of antagonism by capsazepine of the behavioural antinociceptive properties of capsaicin and provides further evidence that capsaicin acts to reduce nociceptive thresholds via a specific receptor. PMID- 1422584 TI - Rabbit isolated renal artery contractions by some tryptamine derivatives, including 2-methyl-5-HT, are mediated by a 5-HT1-like receptor. AB - 1. Despite the fact that 5-hydroxytryptamine (5-HT)-induced contractions of the rabbit isolated renal artery are mediated by a receptor belonging to the heterogeneous 5-HT1-like category, we observed that the so-called selective 5-HT3 receptor agonist, 2-methyl-5-HT, caused a concentration-dependent contraction of this vessel. This study was therefore undertaken to analyze the effects of 2 methyl-5-HT in the renal artery segments, either quiescent or precontracted with U46619 (10(-7) M). alpha-Methyl-5-HT and 5-methoxytryptamine, which have high affinities for 5-HT2 and 5-HT4 receptors, respectively, were used for comparison. 2. In the precontracted vessel segments, the maximum contractile responses obtained with 2-methyl-5-HT, alpha-methyl-5-HT, 5-methoxytryptamine and 5-HT were similar to those in the quiescent segments. However the pD2 values were higher in the precontracted segments, making them about 4-100 fold more sensitive. 3. Neither MDL 72222 (10(-6) M) nor tropisetron (3 x 10(-6) M) suppressed renal artery contractions elicited by 5-HT, 2-methyl-5-HT, alpha-methyl-5-HT or 5 methoxytryptamine, thus ruling out the involvement of 5-HT3 as well as 5-HT4 receptors. 4. On the other hand, both methiothepin (10(-8) and 10(-7) M) and ketanserin (10(-7) and 10(-6) M) caused a rightward shift of agonist concentration-effect curves.The two antagonists had similar pA2 values against the different agonists tested on either quiescent or precontracted vessels, but ketanserin (apparent pA2: 6.6 to 7.0) was between 20-100 fold less potent than methiothepin (apparent pA2: 8.4 to 8.8).5. The results of this functional study permit us to conclude that the contractile effects of 2-methyl-5-HT as well as ct methyl-5-HT and 5-methoxytryptamine on the rabbit isolated renal artery are mediated by a 5-HT1-like receptor. Since, in addition, the reported ligand binding affinity of 2-methyl-5-HT at 5-HT3 receptors is similar to both the ligand binding affinity and the functional pD2 at 5-HTI sites, this compound cannot be regarded as a selective 5-HT3 receptor agonist. Similarly, a-methyl-5 HT and 5-methoxytryptamine have only a limited selectivity for 5-HT2 and 5-HT4 receptors, respectively. PMID- 1422586 TI - Activation of P1- and P2Y-purinoceptors by ADP-ribose in the guinea-pig taenia coli, but not of P2X-purinoceptors in the vas deferens. AB - 1. The activity of adenosine 5'-diphosphoribose (ADP-ribose), a ribosylated purine nucleotide, was investigated on the carbachol-contracted taenia coli, a tissue possessing P1- (A2) and P2Y-purinoceptors and on the guinea-pig vas deferens which possesses P2X-purinoceptors. 2. In the vas deferens, where ATP (1 microM-1 mM) produced concentration-dependent contractions, ADP-ribose was without effect at concentrations up to 1 mM. 3. In the taenia coli, ADP-ribose (0.1 microM-1 mM) produced concentration-dependent relaxations with a potency similar to that of adenosine, but less than that of ATP. The pD2 values for ADP ribose, adenosine and ATP were 4.5 +/- 0.07 (27), 4.4 +/- 0.10 (9) and 5.5 +/- 0.14 (21), respectively. The time-course of the relaxations elicited by ADP ribose was found to be significantly longer than that for ATP and significantly shorter than that for adenosine. 4. The P1-purinoceptor antagonist, 8 phenyltheophylline (5 microM), produced parallel rightward shifts in the concentration-response curves of the relaxations of the taenia coli elicited by ADP-ribose and adenosine but not ATP. 5. Dipyridamole (0.3 microM), a purine nucleoside uptake inhibitor, potentiated the responses to adenosine and ADP ribose in the taenia coli. These potentiations were sensitive to 8 phenyltheophylline (5 microM). 6. Reactive blue 2, a P2Y-purinoceptor antagonist, antagonized the inhibitory responses of ADP-ribose and ATP in the taenia coli, without significantly altering the inhibitory responses of either adenosine or noradrenaline.7. In the presence of the potassium channel blocker, apamin (0.3 microM), the inhibitory responses of ADP-ribose were severely attenuated, and the inhibitory responses of ATP in the taenia coli were converted to transient contractions. Further addition of 8-PT blocked the residual responses of ADPribose.8. The P2-purinoceptor antagonist, suramin (500 microM), antagonized responses to ATP and ADP-ribose,but not adenosine. Further addition of 8-PT antagonized the residual responses to ADP-ribose, but not to ATP.9. It is concluded that ADP-ribose has a mixed pharmacological profile, evoking both PI (A2)-purinoceptor-mediated responses and P2Y-purinoceptor-mediated responses, while being inert at P2Xpurinoceptors.It is suggested that ADP-ribose may provide a useful starting point for the generation of structural analogues which have specific activity at the P2Y-purinoceptor. PMID- 1422587 TI - Calmodulin antagonists inhibit endothelium-dependent hyperpolarization in the canine coronary artery. AB - 1. The effects of the calmodulin antagonists, calmidazolium and fendiline were investigated on endothelium-dependent hyperpolarization in the canine coronary artery. The membrane potential of vascular smooth muscle cells was measured with the microelectrode technique. 2. Smooth muscle cells of the canine coronary artery had a resting membrane potential of -50 mV. Bradykinin and the Ca(2+) ionophore, A23187, induced concentration- and endothelium-dependent hyperpolarization. The hyperpolarization induced by a supramaximal concentration of bradykinin (10(-6) M) reached approximately 20 mV. 3. Calmidazolium (10(-5) M) and fendiline (10(-4) M) inhibited hyperpolarization induced by bradykinin and A23187. By contrast, calmidazolium did not affect the hyperpolarization induced by lemakalim, an opener of ATP-sensitive K(+)-channels. 4. These observations suggest that calmodulin is involved in the generation of endothelium-dependent membrane hyperpolarization of vascular smooth muscle. PMID- 1422588 TI - Endothelium-dependent relaxation and noradrenaline sensitivity in mesenteric resistance arteries of streptozotocin-induced diabetic rats. AB - 1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries of control and streptozotocin induced diabetic rats. 2. The diabetic rats demonstrated enhanced vascular sensitivity to noradrenaline compared with age-matched controls (pEC50 5.99 +/- 0.06 for diabetic rats, n = 25, versus 5.82 +/- 0.03 for controls, n = 45, P < 0.05). 3. Significant impairment of acetylcholine-induced relaxation was observed in arteries from the diabetic animals compared with controls (pEC50 6.81 +/- 0.17 for diabetic rats, n = 21, versus 7.54 +/- 0.17 for controls, n = 45, P < 0.001). 4. The difference between acetylcholine-induced relaxation in diabetic and control arteries remained in the presence of 10 microM indomethacin (pEC50 6.41 +/- 0.11 for diabetic rats, n = 16, versus 7.59 +/- 0.08 for controls, n = 20, P < 0.001). 5. The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L NMMA, 1 mM) produced profound inhibition of acetylcholine-induced relaxation in diabetic arteries but partial inhibition in controls. The incomplete inhibition of acetylcholine-induced relaxation by L-NMMA in the control arteries was the result of ineffective inhibition of nitric oxide synthase since an alternative inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM), led to similar inhibition to that seen in the diabetic arteries with L-NMMA. The endothelium derived relaxing factor (EDRF)-mediated component of acetylcholine-induced relaxation determined by use of the nitric oxide synthase inhibitors was, therefore, apparently reduced in diabetic rats compared with control animals.6. In further experiments L-NAME was found to enhance the response to noradrenaline in control rats but not in diabetic animals, suggesting that the abnormal response to noradrenaline in the diabetic animals was also due to reduced EDRF release.7. Nitroprusside-induced relaxation (endothelium-independent) was similar in arteries from control anddiabetic rats (pEC5o 7.61 +/- 0.13 for diabetic arteries, n = 18, versus 7.68 +/- 0.15 in the controls, n = 20, P not significant).8. These results suggest that endothelial function is abnormal in mesenteric resistance arteries of streptozotocin-induced diabetic rats and that this is predominantly due to reduced EDRF release. PMID- 1422589 TI - Reduced relaxant potency of nitroprusside on pulmonary artery preparations taken from rats during the development of hypoxic pulmonary hypertension. AB - 1. Relaxant responses to nitroprusside were examined on U46619-contracted pulmonary artery ring preparations from rats exposed to hypoxia, in chambers containing 10% oxygen, for 1, 3, or 14 days, or for 14 days followed by 12 days in room air. Control rats were housed in room air. 2. After 3 days of hypoxia (but not 1 day), rats had elevated pulmonary artery pressure, right ventricular hypertrophy and polycythemia. After 14 days of hypoxia there was, in addition, hypertrophy of the pulmonary artery. In rats returned to room air for 12 days after 14 days of hypoxia, there was still some right ventricular and vascular hypertrophy but no increase in pulmonary artery pressure or polycythemia. 3. The potency (neg log EC50) of nitroprusside on pulmonary arteries taken from rats after 3 or 14 days of hypoxia was significantly less than on preparations from control rats (3 and 11 fold, respectively). This was not seen after 1 day of hypoxia or after 14 days of hypoxia followed by 12 days in room air. Removal of the endothelium from the preparations had no effect on the potency of nitroprusside in control or hypoxic rats (14 days). 4. In preparations from hypoxic, but not control, rats (14 days), the maximum response to nitroprusside was > 100% (177% reversal of the U46619 contraction) in the absence, but not in the presence, of the endothelium, indicating that pulmonary arteries from hypoxic rats had inherent tone which could be counteracted by a relaxing factor from the endothelium. 5. Exposure of rats to hypoxia (14 days) did not affect the potency of nitroprusside on aorta or trachea.6. It is concluded that exposure of rats to hypoxia results in reversible desensitization of the vascular smooth muscle of pulmonary artery to nitroprusside. The time course of this desensitization suggests that it is probably associated with the elevated pulmonary artery pressure or maintained hypoxaemia rather than with the vascular hypertrophy.7. It is postulated that the increase in pulmonary artery pressure and/or the maintained hypoxaemia may cause chronic release of nitric oxide from the pulmonary vascular endothelium or smooth muscle resulting in desensitization of soluble guanylate cyclase to the action of nitroprusside. PMID- 1422590 TI - Effect of the thromboxane A2-mimetic U46619 on 5-HT1-like and 5-HT2 receptor mediated contraction of the rabbit isolated femoral artery. AB - 1. The influence of the thromboxane A2-mimetic U46619 (11 alpha, 9 alpha epoxymethano PGH2) on 5-hydroxy-tryptamine (5-HT)-induced contractions of the rabbit isolated femoral artery has been examined. 2. In the absence of U46619, 5 HT responses were mediated predominantly by 5-HT2-receptors as judged by potent, surmountable antagonism by the selective 5-HT2 receptor antagonists, spiperone and ketanserin. Both antagonists unmasked a population of 5-HT1-like receptors which accounted for approximately 10-15% of the 5-HT maximum response. 3. In the presence of U46619 (3-10 nM), 5-HT-induced contractions were largely resistant to blockade by 5-HT2 receptor antagonists since 5-HT1-like receptor-mediated contraction now accounted for approximately 60% of the 5-HT maximum response. 4. These results show that activation of thromboxane A2 receptors in a tissue possessing both 5-HT2 and 5-HT1-like receptors can convert 5-HT-induced contraction from one mediated predominantly by 5-HT2 receptors to one which is mediated predominantly by 5-HT1-like receptors. PMID- 1422591 TI - Short-term desensitization of the histamine H1 receptor in human HeLa cells: involvement of protein kinase C dependent and independent pathways. AB - 1. In this study we have investigated the effects of short-term exposure of cells to histamine on the subsequent H1 receptor responsiveness in HeLa cells, using Ca2+ fluorescence microscopy and video digital imaging. 2. In HeLa cells, histamine (100 microM) induces an immediate H1 receptor-mediated biphasic elevation of the intracellular Ca2+ concentration ([Ca2+]i) (basal [Ca2+]i: 81 +/ 30 nM, histamine-induced Ca2+ response: first phase: 1135 +/- 79 nM; second phase: 601 +/- 52 nM, n = 11). 3. The histamine H1 receptors on HeLa cells are readily susceptible to desensitization since repetitive exposure of the same group of cells to histamine (100 microM) markedly affected the release and influx component of the induced Ca2+ response (second application of histamine: first phase: 590 +/- 92 nM, second phase: 279 +/- 47 nM; third application of histamine: first phase: 454 +/- 127 nM, second phase: 240 +/- 45 nM, n = 6). Video digital imaging revealed an increase in the lag time between stimulation and monitoring of the Ca2+ response and a reduced increase in [Ca2+]i after desensitization with histamine. 4. Neither the release component of the ATP response (50 microM) nor the caffeine (3 mM)-induced Ca2+ release were found to be affected by desensitization with 100 microM histamine. However, the second phase of the ATP response was significantly reduced after desensitization with histamine (control cells: 516 +/- 33 nM; desensitized cells: 331 +/- 96 nM, n = 4, P < 0.05).5. Activation of protein kinase C (PKC) by phorbol-12-myristate-1 3 acetate was found to inhibit the histamine as well as ATP-induced Ca2" response in a dose-dependent manner.6. In PKC downregulated cells the second phase of the histamine-induced Ca2+ response was significantly elevated, indicating the involvement of PKC in the negative feedback on the Ca2+ influx(control cells: second phase: 601 +/- 52 nM (n = 11); PKC downregulated cells: second phase:890 +/- 90nM, n = I0, P<0.05).7. Homologous desensitization of H, receptor responsiveness was still observed in PKC downregulated cells, implying the rapid activation of a regulatory mechanism other than PKC.8. Based on our experimental data we suggest that short-term desensitization of the histamine H,receptor evolves from two different processes: a selective reduction of the histamine induced Ca2+ release, mediated by a PKC-independent pathway, and a non-selective inhibition of the receptormediated Ca2+ influx activated by a PKC-dependent pathway. PMID- 1422592 TI - The effect of SK&F 95654, a novel phosphodiesterase inhibitor, on cardiovascular, respiratory and platelet function. AB - 1. SK&F 95654 inhibited the guanosine 3':5'-cyclic monophosphate (cyclic GMP) inhibited phosphodiesterase (cGI-PDE) with an IC50 value of 0.7 microM. The IC50 values were greater than 100 microM for the other four phosphodiesterase isoenzymes tested. The R-enantiomer of SK&F 95654 (IC50 = 0.35 microM) was a more potent inhibitor of cGI-PDE than was the S-enantiomer (IC50 = 5.3 microM). 2. In the guinea-pig working heart, SK&F 95654 produced a positive inotropic response without altering heart rate. 3. Oral administration of SK&F 95654 to conscious dogs caused dose-dependent increases in left ventricular dp/dtmax in the range 10 50 micrograms kg-1. These positive inotropic responses were maintained for 3 h without simultaneous changes in heart rate or blood pressure. The peak effects on left ventricular dp/dtmax were similar for orally and intravenously administered compound, indicating good oral bioavailability. 4. SK&F 95654 caused a potent inhibition of U46619-induced aggregation in both a human washed platelet suspension (WPS) (IC50 = 70 nM) and in human platelet-rich plasma (PRP) (IC50 = 60 nM), indicating that the compound shows negligible plasma binding. 5. The R enantiomer of SK&F 95654 was twenty fold more potent as an inhibitor of platelet aggregation than was the S-enantiomer. The similarity of this ratio to that obtained on the cGI-PDE suggests that SK&F 95654 inhibits platelet aggregation via its effects on cGI-PDE. This was also indicated by studies which showed that SK&F 95654 increased adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels and activated cyclic AMP-dependent protein kinase in human platelets. 6. Collagen induced aggregation of rat PRP was also inhibited by SK&F 95654 (ICso = 65 nM). The effects of SK&F 95654, administered intravenously, on ex vivo platelet aggregation were studied in the conscious rat. At 1 mg kg-', SK&F 95654 inhibited aggregation for at least 4 h post dose and was more potent than the two other cGI PDE inhibitors studied (siguazodan and SK&F 94120).7. In contrast to its potent effects on heart and platelets, SK&F 95654 caused only a modest relaxation of histamine- or U46619-induced bronchoconstriction in the anaesthetized, ventilated guinea-pig.8. Taken together, these results indicate that SK&F 95654 may be a suitable agent for the treatment of congestive heart failure. PMID- 1422593 TI - NG-hydroxy-L-arginine prevents the haemodynamic effects of nitric oxide synthesis inhibition in the anaesthetized rat. AB - 1. We have investigated the effects of L-hydroxy-L-arginine (L-HOArg), an intermediate in the biosynthesis of nitric oxide (NO) from L-arginine (L-Arg), on the haemodynamic effects (systemic blood pressure and renal blood flow) of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the anaesthetized rat. 2. L-Arg or L-HOArg (3 mg kg-1 min-1), but not D-arginine (D Arg) or NG-hydroxy-D-arginine (D-HOArg), elicited a slight but significant increase in total renal blood flow (RBF) of 11 +/- 2% and 11 +/- 1%. Since mean arterial blood pressure (MAP) did not change this dose of L-Arg or L-HOArg resulted in a reduced renal vascular resistance (RVR) of the same magnitude. 3. Bolus injections of L-NAME, at 0.3 or 1 mg kg-1 i.v., produced a significant fall in RBF of 11 +/- 2% and 32 +/- 5% and an increase in MAP of 7 +/- 3 mmHg and 22 +/- 5 mmHg, respectively. Consequently, RVR was elevated by 21 +/- 5% and 52 +/- 10%. 4. L-Arg or L-HOArg (3 mg kg-1 min-1) reduced the L-NAME-induced (0.3 or 1 mg kg-1) falls in RBF and increases in RVR by more than 65%. Neither D-Arg nor D HOArg (3 mg kg-1 min-1) had any significant effect on the changes in RBF or RVR induced by L-NAME. 5. L-Arg or L-HOArg (3 mg kg-' min-') attenuated the pressor effect of L-NAME (3 mg kg-') by 73% and 64%, respectively, while neither the D isomer of arginine nor hydroxyarginine had any effect.6. These results demonstrate that L-HOArg antagonizes the haemodynamic effects of NO-biosynthesis inhibition in vivo, thus supporting the hypothesis that L-HOArg is an intermediate in the formation of NO from L-Arg. PMID- 1422594 TI - Cytosolic calcium increase in coronary endothelial cells after H2O2 exposure and the inhibitory effect of U78517F. AB - 1. Cytosolic calcium concentrations ([Ca2+]i) were determined with fura-2 on both resting (unstimulated) and A23187-stimulated coronary endothelial cells following injury by hydrogen peroxide (H2O2). 2. Treatment of cells with H2O2 (10(-4) M) caused an increase in the resting [Ca2+]i, which reached a maximum of five fold after 3 h. 3. The increase in resting [Ca2+]i was significantly attenuated by treatment with U78517F, a potent inhibitor of lipid peroxidation, at a concentration of 10(-6) M or greater. Catalase (50 u ml-1) also markedly inhibited the H2O2-induced rise in [Ca2+]i. Pretreatment with verapamil (10(-5) M), nifedipine (10(-6) M) or diltiazem (10(-5) M) had no effect on the increase in [Ca2+]i following addition of H2O2. 4. A23187 produced a transient increase in [Ca2+]i followed by a sustained plateau. The initial peak and plateau phase responses to A23187 were augmented by H2O2. This augmentation of [Ca2+]i was suppressed by U78517F or catalase but not by Ca-entry blockers. 5. Thus, it is likely that lipid peroxidation plays a critical role in the sustained increase in [Ca2+]i that occurs following treatment with H2O2 and that this continues in the presence of agonists which stimulate the endothelium. Voltage-gated Ca2+ channels do not seem to be involved in the genesis of cellular damage associated with sustained large increases in [Ca2+]i. PMID- 1422595 TI - L-689,660, a novel cholinomimetic with functional selectivity for M1 and M3 muscarinic receptors. AB - 1. L-689,660, 1-azabicyclo[2.2.2]octane, 3-(6-chloropyrazinyl)maleate, a novel cholinomimetic, demonstrated high affinity binding (pKD (apparent) 7.42) at rat cerebral cortex muscarinic receptors. L-689,660 had a low ratio (34) of pKD (apparent) values for the displacement of binding of the antagonist ([3H]-N methylscopolamine ([3H]-NMS) compared with the displacement of the agonist [3H] oxotremorine-M ([3H]-Oxo-M), in rat cerebral cortex. Low NMS/Oxo-M ratios have been shown previously to be a characteristic of compounds that are low efficacy partial agonists with respect to stimulation of phosphatidyl inositol turnover in the cerebral cortex. 2. L-689,660 showed no muscarinic receptor subtype selectivity in radioligand binding assays but showed functional selectivity in pharmacological assays. At M1 muscarinic receptors in the rat superior cervical ganglion, L-689,660 was a potent (pEC50 7.3 +/- 0.2) full agonist in comparison with (+/-)-muscarine. At M3 receptors in the guinea-pig ileum myenteric plexus longitudinal muscle or in trachea, L-689,660 was again a potent agonist (pEC50 7.5 +/- 0.2 and 7.7 +/- 0.3 respectively) but had a lower maximum response than carbachol. In contrast L-689,660 was an antagonist at M2 receptors in guinea-pig atria (pA2 7.2 (95% confidence limits 7, 7.4)) and at muscarinic autoreceptors in rat hippocampal slices. 3. The putative M1-selective muscarinic agonist, AF102B (cis-2-methylspiro-(1,3-oxathiolane 5,3')-quinuclidine hydrochloride) was found to have a profile similar to L-689,660 but had up to 100 times less affinity in binding and functional assays.RS-86 (2-ethyl-8-methyl-2,8-diazospiro[4,5]decan 1,3-dionehydrochloride) also had lower affinity than L-689,660, and had no binding selectivity for muscarinic receptor subtypes. RS-86 had a higher NMS/Oxo M ratio than L-689,660 and was a full agonist at MI,M2 and M3 receptors in the functional pharmacological assays.4. The functional selectivity of L-689,660 in muscarinic pharmacological assays is consistent with the effects of a low efficacy partial agonist in tissues with different effective receptor reserves. PMID- 1422596 TI - Effects of long-term oral administration of amiodarone on the electromechanical performance of rabbit ventricular muscle. AB - 1. The effects of long-term administration of oral amiodarone on transmembrane action potential and contraction of ventricular muscle were investigated in rabbits. 2. ECGs of rabbits that received oral amiodarone 50 mg or 100 mg kg-1 daily for 4 weeks, showed a significant prolongation of RR, QT and corrected QT (QTc) intervals, whereas PQ and QRS were unaffected. Serum and myocardial tissue amiodarone concentrations were 0.14-0.18 micrograms ml-1 and 1.47-3.63 micrograms g-1 wet wt. respectively. 3. Right ventricular papillary muscles isolated from treated rabbits were characterized by a moderate prolongation of action potential duration (APD) compared with controls. A slight decrease of the maximum upstroke velocity (Vmax) was also observed at the higher dose. The APD prolongation by chronic amiodarone, unlike acute effects of sotalol, E-4031, Cs+ and 4 aminopyridine, did not show marked reverse use-dependence. 4. APD and Vmax restitution following slow basic stimuli (0.03 Hz) were unaffected by chronic treatment with amiodarone. 5. Acute application of amiodarone (10 microM) caused a significant decrease in APD and developed tension, as well as a marked use dependent Vmax inhibition with fast recovery kinetics. 6. These findings suggest that a major and consistent electro-physiological effect of chronic amiodarone is repolarization delay (Class-III action) showing minimal frequency-dependence. However, when amiodarone above a certain concentration is present in the extracellular space, a fast kinetic Class-I action would be added as an acute effect. PMID- 1422597 TI - Electrophysiological effects of CRE-1087 in guinea-pig ventricular muscles. AB - 1. The electrophysiological effects of CRE-1087, a new antiarrhythmic drug, were studied in guinea-pig papillary muscles. 2. CRE-1087 (10(-7) M-10(-4) M) produced a concentration-dependent decrease in the action potential amplitude and Vmax of the upstroke without altering the action potential duration or the resting membrane potential. 3. At 5 x 10(-6) M, CRE-1087 produced a 5.0 +/- 1.0% tonic Vmax block and this value was not modified at the different rates of stimulation tested. In the presence of CRE-1087, trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in Vmax (frequency-dependent Vmax block) which augmented at higher rates of stimulation. At 2 Hz the onset kinetics of the frequency-dependent Vmax block was fitted by a monoexponential function being the K value 0.099 +/- 0.012 AP-1. The time constant for the recovery of Vmax from the frequency-dependent block was prolonged to 18.3 +/- 1.5 s. 4. CRE-1087 (5 x 10( 6) M) did not shift the membrane responsiveness curve. 5. CRE-1087 had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 mM KCl, which suggested that CRE-1087 did not exhibit class IV (Ca antagonist) antiarrhythmic actions. 6. The slow onset and the slow offset kinetics of frequency-dependent Vmax block during repetitive activity suggested that in guinea-pig ventricular muscle fibres CRE-1087 exhibited class Ic antiarrhythmic actions. PMID- 1422598 TI - Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin. AB - 1. Capsazepine is a synthetic analogue of the sensory neurone excitotoxin, capsaicin. The present study shows the capsazepine acts as a competitive antagonist of capsaicin. 2. Capsazepine (10 microM) reversibly reduced or abolished the current response to capsaicin (500 nM) of voltage-clamped dorsal root ganglion (DRG) neurones from rats. In contrast, the responses to 50 microM gamma-aminobutyric acid (GABA) and 5 microM adenosine 5'-triphosphate (ATP) were unaffected. 3. The effects of capsazepine were examined quantitatively with radioactive ion flux experiments. Capsazepine inhibited the capsaicin (500 nM) induced 45Ca2+ uptake in cultures of rat DRG neurones with an IC50 of 420 +/- 46 nM (mean +/- s.e.mean, n = 6). The 45Ca2+ uptake evoked by resiniferatoxin (RTX), a potent capsaicin-like agonist was also inhibited. (Log concentration)-effect curves for RTX (0.3 nM-1 microM) were shifted in a competitive manner by capsazepine. The Schild plot of the data had a slope of 1.08 +/- 0.15 (s.e.) and gave an apparent Kd estimate for capsazepine of 220 nM (95% confidence limits, 57 400 nM). 4. Capsazepine also inhibited the capsaicin- and RTX-evoked efflux of 86Rb+ from cultured DRG neurones. The inhibition appeared to be competitive and Schild plots yielded apparent Kd estimates of 148 nM (95% confidence limits, 30 332 nM) with capsaicin as the agonist and 107 nM (95% confidence limits, 49-162 nM) with RTX as agonist. 5. A similar competitive inhibition by capsazepine was seen for capsaicin-induced [14C]-guanidinium efflux from segments of adult rat vagus nerves (apparent Kd = 690 nM; 95% confidence limits, 63 nM-1.45 microM). No significant difference was noted in the apparent Kd estimates for capsazepine in assays on cultured DRG neurones and vagus nerve as shown by the overlap in the 95% confidence limits.6. Capsazepine, at concentrations up to 1O microM, had no significant effects on the efflux of 86Rb+ from cultured DRG neurones evoked either by depolarization with high (50 mM) K' solutions or by acidification of the external medium to pH 5.0-5.6. Similarly capsazepine had no significant effect on he depolarization (50 mM KCl)-induced efflux of [14C]-guanidinium from vagus nerve preparations.7. Ruthenium Red was also tested for antagonism against capsaicin evoked ['4C]-guanidinium release from vague nerves and capsaicin induced 45Ca2" uptake in cultures of DRG neurones. In contrast to capsazepine the inhibition by Ruthenium Red (10-500nM in DRG and 0.5-10microM in vagus nerve experiments) was not consistent with a competitive antagonism, but rather suggested a more complex,non-competitive inhibition. PMID- 1422599 TI - Inhibition by phosphoramidon of the regional haemodynamic effects of proendothelin-2 and -3 in conscious rats. AB - 1. Regional haemodynamic studies were carried out in conscious, Long Evans rats, chronically-instrumented with pulsed Doppler flow probes and intravascular catheters. 2. In the first experiment, proendothelin-2 and -3 (0.1 and 1.0 nmol kg-1, i.v. boluses) were found to cause dose-dependent pressor, bradycardic, and renal and, particularly, mesenteric vasoconstrictor effects. The hindquarters showed an initial vasodilatation (which was not dose-dependent) followed by a vasoconstriction (which was dose-related). The pressor and renal and mesenteric vasoconstrictor effects of proendothelin-3 were greater than those of proendothelin-2. 3. In the second experiment, it was demonstrated that phosphoramidon (10 mumol kg-1, i.v. bolus) abolished the pressor, bradycardiac, and hindquarters vasoconstrictor effects of proendothelin-2 (1.0 nmol kg-1), and inhibited significantly the renal and mesenteric vasoconstrictor actions of this peptide. Phosphoramidon had similar effects on the responses to proendothelin-3 (1.0 nmol kg-1), although a slight pressor effect of this peptide remained in the presence of phosphoramidon. 4. In the third experiment, it was found that phosphoramidon had no significant effect on the pressor or vasoconstrictor responses to endothelin-2 or -3 (0.1 nmol kg-1). 5. Collectively, the results indicate that the haemodynamic effects of proendothelin-2 and -3 in vivo in conscious rats are probably due to their conversion to endothelin-2 and -3, respectively, by an enzyme(s) that is inhibited by phosphoramidon. There appears to be no obvious difference between proendothelin-2, proendothelin-3 and proendothelin-1 in this respect. PMID- 1422600 TI - 5-Hydroxytryptamine (5-HT) mediates potent relaxation in the sheep isolated pulmonary vein via activation of 5-HT4 receptors. AB - 1. We investigated the potent 5-hydroxytryptamine (5-HT)-mediated vasorelaxation of the sheep pulmonary vein. Here we present evidence that this response is due to activation of 5-HT4 receptors. 2. 5-HT (1-1000 nM) caused concentration dependent, maintained relaxations (pEC50 = 8.4 +/- 0.1) of isolated rings of sheep pulmonary vein pre-contracted with endothelin-1 (3 nM). 3. The relaxation response to 5-HT was unaffected by either removal of the endothelium or by inhibition of NO-synthase by NG-nitro-L-arginine (100 microM). 4. Ketanserin, methiothepin, methysergide and MDL 72222 at concentrations that selectively block 5-HT2, 5-HT1-like and 5-HT3 receptors respectively, had no effect on the concentration-relaxation curve to 5-HT. 5. ICS 205-930 (1-10 microM) competitively antagonized the concentration-relaxation curve to 5-HT with a pA2 of approximately 6.7. 6. Increasing the concentration of ICS 205-930 from 10 to 30 microM did not cause a further rightward shift of the 5-HT concentration relaxation curve. The pEC50 of 6.50 for 5-HT in the presence of ICS 205-930 (30 microM) was taken as an estimate of the affinity of 5-HT for 5-HT1-like receptors since methiothepin (10 nM) unmasked further competitive inhibition of 5-HT in the presence of this concentration of ICS 205-930. 7. Other 5-HT agonists including 5 carboxamidotryptamine (5-CT), alpha-methyl-5-HT and BIMU 8 (but not 2-methyl-5 HT) also relaxed the pulmonary vein.The response to 5-CT was inhibited by methiothepin (10 nM) and methysergide (100 nM) but unaffected by ICS 205-930 (30 microM), whilst that toa-methyl-5-HT and BIMU 8 was unaffected by methiothepin (10 nM) but blocked by ICS 205-930(estimated pKB values of 6.4 and 6.9 respectively). Relaxation curves to both 5-HT and BIMU 8 were unaffected by cocaine (6 microM).8. In conclusion, these results indicate that the sheep pulmonary vein possesses 5-HT4 receptors that mediate potent endothelium independent relaxation. 5-HT,-like relaxant receptors are also present in this tissue but 5-HT has a lower affinity at these receptors. This preparation may thus provide a robust and sensitive bioassay for future development of selective 5-HT4 receptor agonists and antagonists. PMID- 1422601 TI - The role of endothelial cells in the relaxations induced by 13-hydroxy- and 13 hydroperoxylinoleic acid in canine arteries. AB - 1. One of the major fatty acids in the arterial wall is linoleic acid. It has been shown that its 13-hydroxy metabolite (13-HODE) is generated in significant amounts by cultured endothelial cells. The aim of the present study was to investigate the relaxations to 13-HODE and its hydroperoxyprecursor (13-HPODE) and to examine the role of the endothelial cells. 2. Ring segments of canine circumflex and splenic artery were mounted in organ chambers for isometric tension recording. During contractions induced by prostaglandin F2 alpha or noradrenaline, 13-HODE and 13-HPODE evoked dose-dependent relaxations. Removal of the endothelial cells reduced the relaxations to 13-HODE, but had no effect on those elicited by 13-HPODE. 3. Indomethacin and meclofenamate (0.3 microM to 30 microM) blocked the relaxations evoked by 13-HODE and 13-HPODE in endothelium denuded rings. In segments with endothelium, both cyclo-oxygenase inhibitors again abolished the relaxations to 13-HODE, but only diminished those to 13 HPODE. 4. Prostacyclin biosynthesis, as measured by radioimmunoassay, increased upon incubation with 13-HODE and 13-HPODE (10 microM). Bioassay of the release of nitric oxide (NO) indicated that NO was not involved in the relaxations elicited by either metabolite. Moreover, L-NG-nitroarginine (100 microM), a specific inhibitor of NO synthesis, did not influence the relaxations to 13-HODE and 13 HPODE. The responses to 13-HPODE were also not altered by superoxide dismutase. 5. In the splenic artery 13-HPODE and 13-HODE induced contractions above 3 microM which were blocked by the thromboxane receptor antagonist, daltroban.In the circumflex artery contractile responses to high concentrations of 13-HODE could be observed only after inhibition of cyclo-oxygenase.6. We conclude that the vasodilatation induced by 13-HODE and 13-HPODE was due to stimulation of prostacyclin biosynthesis both in the endothelium and smooth muscle cells or other subendothelial structures. An additional, unidentified intermediate, which was neither NO nor a cyclo-oxygenase product nor superoxide anion, contributed to the relaxations to 13-HPODE in arteries with endothelium. PMID- 1422602 TI - In vitro denervation of the rat vas deferens through hypothermic storage. AB - 1. The rat vas deferens was excised, stored at 4-6 degrees C and tested after 24, 48, 72 or 96 h for its contractile activity and for the presence of innervation. 2. The maximal contractile capacity of the vas, tested through cumulative concentrations of barium chloride (3 x 10(-2) M) was progressively reduced from about 110 mm to about 63 mm after 72 h, without further decay after 96 h. Spontaneous rhythmic contractions were practically absent. 3. A loss of endogenous pools of catecholamines was indicated by four parameters: (a) a decline of about 80% after 24 h and of more than 95% after 48 h of the contractile effect of the indirect sympathomimetic agonist tyramine; (b) a fall of about 20%, 50% and 85% on the concentration of noradrenaline, respectively after 24, 48 and 72 h; (c) a fall of about 25% and 90% after respectively 24 and 48 h, of the activity of dopamine-beta-hydroxylase (DBH); (d) a decline of noradrenaline-induced histofluorescence on cross sections of the vas. 4. A loss of neuronal uptake capacity was indicated by: (a) a progressive variation of the apparent affinity for adrenaline, expressed as pD2 values, that increased by about 1.5 log units (corresponding to a 30 fold potentiation) after 72 h, and (b) a reduction of the ability of cocaine to potentiate the contractile effects of adrenaline. 5. The pD2 values for barium chloride, 5-hydroxytryptamine (5-HT) and histamine were not significantly changed, while the corresponding value for acetylcholine was slightly but significantly reduced by about 0.8 log units. 6. The maximal heights of concentration-response curves for noradrenaline, acetylcholine, histamine and 5-HT were reduced by 42-66% in relation to controls. However, when this reduction was measured in relation to the corresponding barium effect, by means of the relative responsiveness ratio (p), a small though significant increase was observed for noradrenaline, and a fall for the other drugs.7. It is concluded that: (1) the values for the various biochemical and pharmacological parameters decline at different rates, though revealing altogether that denervation is completed by at least 85% after 72 h of hypothermic storage; (2) two of the results, i.e., the lack of spontaneous rhythmic contractions and the lack of increased contractile effects for acetylcholine, 5-HT and histamine, indicate that in these conditions the vas is devoid of the so-called nonspecific signs of denervation. PMID- 1422603 TI - Endothelium-dependent modulation of resistance vessel contraction: studies with NG-nitro-L-arginine methyl ester and NG-nitro-L-arginine. AB - 1. The effect of NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L arginine (L-NOARG) on noradrenaline (NA)-induced contractility and acetylcholine (ACh)-induced endothelium-dependent relaxation was studied in rat mesenteric resistance arteries. 2. Third order branches of mesenteric arteries were dissected and mounted on two forty micron wires in a Mulvany myograph. 3. Incubation with L-NAME and L-NOARG (10 microM) caused a time-dependent shift in the 50% response to NA (ED50) (0.01 microM-10 microM) but was not associated with an increase in the maximum contractile response. 4. L-NAME and L-NOARG (10 microM) caused a time-dependent inhibition of ACh (1 microM)-induced relaxation with a maximum effect after 120 min. 5. Following endothelium removal, incubation with either L-NAME or L-NOARG caused no significant shift in the ED50, although the residual relaxation response to ACh (1 microM) was further attenuated. 6. Incubation with the cyclo-oxygenase inhibitor, indomethacin, enhanced the relaxation to ACh and reduced the inhibitory effects of L-NAME and L-NOARG. 7. In conclusion, L-NAME and L-NOARG are potent inhibitors of acetylcholine-induced endothelium-dependent relaxation in mesenteric resistance arteries. The shift in ED50 associated with these inhibitors suggests a probable role for the endothelium in modulating the contractility of the resistance vasculature. PMID- 1422604 TI - Mental health services in transition: the United States and the United Kingdom. PMID- 1422605 TI - Sociology in the context of social psychiatry. PMID- 1422606 TI - The assessment of insight in psychosis. AB - An assessment schedule was used to determine the nature of insight in 91 mixed psychotic patients, and to examine its distribution and associations. While all the components of the schedule intercorrelated significantly, scores for compliance were only weakly related to those for ability to label psychotic phenomena as abnormal. Compliance and illness recognition were related to IQ. Total insight score was inversely correlated, moderately, with a global measure of psychopathology derived from the PSE, and was less in patients involuntarily committed. Age, sex, diagnosis, and the number of previous hospital admissions had little effect. The results support the notion that insight is not a unitary concept. PMID- 1422607 TI - The perception of emotion by schizophrenic patients. AB - Studies which have examined the perception of emotion by schizophrenic patients have produced conflicting results, an outcome which may, in part, be due to difficulties in presenting a realistic portrayal of emotion. This study exposed 32 schizophrenic patients in remission and ten controls to five videotaped scenes of emotional situations played by actors. The schizophrenic patients were divided into three groups, namely those living with high-EE relatives, those living with low-EE relatives and those living alone, in order to test the hypothesis that patients in a high-EE environment are less able to identify emotionally charged situations. Measures of electrodermal activity and self-ratings of tension were recorded concomitantly. The schizophrenic patients in all groups were as adept at identifying emotions as were the controls. There was no difference between the groups in electrodermal activity and subjective tension for all video scenes, except for the one which portrayed the only pleasant interaction; the high-EE group was significantly more aroused on both measures, which were independent of each other. PMID- 1422608 TI - Positive and negative symptoms. Relation to familial transmission of schizophrenia. AB - The authors assessed the relevance of clinical symptoms to genetic research in schizophrenia in the nuclear families of 65 chronic schizophrenic probands. The morbidity risk for schizophrenia and schizotypal personality (a 'spectrum' disorder) was markedly reduced in first-degree relatives of probands with predominant negative symptoms, as compared with relatives of probands with other symptom patterns. The data support the notion that negative-symptom schizophrenia has an attenuated genetic component. PMID- 1422609 TI - Life events and schizophrenic relapse after withdrawal of medication. AB - Research with schizophrenic out-patients has shown that antipsychotic medication reduces relapse rates. This protective factor may operate partially by raising the threshold for relapse in the face of environmental stressors such as life events and high levels of familial expressed emotion. A prospective, longitudinal design was employed in the monthly collection of life-events data with 23 recent onset schizophrenic out-patients. In a between-subjects ANOVA, a significantly higher frequency of independent life events was found in the month prior to a relapse for ten patients on medication, as compared with the analogous month for 13 drug-free patients. These findings suggest that neuroleptic medication may produce a prophylactic effect by raising a patient's threshold of vulnerability to relapse. PMID- 1422610 TI - The TAPS project. 6: New long-stay psychiatric patients and social deprivation. AB - The clinical and social characteristics of new long-stay (NLS) patients at Friern and Claybury hospitals are described, together with their accumulation rates within health districts in northeast London, and the associations between accumulation rates and social deprivation. There is a fourfold variation between local districts in annual accumulation rates of NLS patients (between 2.5 and 11 per 100,000 population); 0.55 of this variation is accounted for by the Jarman scores of social deprivation, and 0.81 by local rates of unemployment. Other recent British studies support this finding that measures of social deprivation can statistically explain a large proportion of the variation in treated rates of psychiatric morbidity, and may be useful in predicting needs for psychiatric services. PMID- 1422611 TI - The influence of antidepressants in overdose on the increased suicide rate in Ireland between 1971 and 1988. AB - There has been almost a threefold increase in the incidence of suicide in Ireland during the past 20 years. When each case occurring between 1971 and 1988 was reviewed, the major causes of death were found to be drowning and hanging. Deliberate overdoses with tricyclic antidepressants accounted for less than 4% of all suicides, over the 17 years studied, and during this time, overdose with tricyclics has made a proportionately smaller contribution to the total number of suicides. Greater attention should be paid to identifying and treating the majority of suicidal patients who are at risk by other methods. PMID- 1422612 TI - Salivary testosterone levels and major depressive illness in men. AB - Studies of testosterone levels in patients with major depressive illness have produced varying results, plasma levels usually being reported. Saliva levels reflect 'free' plasma testosterone, and a pilot study of 11 men with major depression with melancholia, who underwent a standard dexamethasone suppression test, is described. There were no significant differences in testosterone levels compared with an age-matched control group. In the patient group, pre dexamethasone levels correlated significantly and negatively with depression ratings on the 21-item Hamilton and the Montgomery and Asberg depression scales, and also with state anxiety measured on the Spielberger scale. PMID- 1422613 TI - Can we predict the persistence of depression? AB - Fifty-five patients with primary major depression were followed up prospectively from time of onset of the index illness episode until recovery. The course of depression in hospital-treated patients was protracted, with a median length of episode of one year. Two factors significantly predicted persistence of symptoms: interval between onset and receipt of treatment, and premorbid neuroticism, which accounted for 55% of the variance in length of episode. PMID- 1422614 TI - Homogamy: the relationships and sexual partners of normal-weight bulimic women. AB - This study reports the demography, weight, and alcohol and psychiatric histories of the sexual partners of 112 consecutive patients with bulimia nervosa, all from an urban catchment area. Seventy-three patients (65%) had a current sexual partner. The partners were of similar social background, but slightly older. On average, partners were overweight (110% of MMPW) and over 27% reported having an eating or weight problem. A quarter of the partners had been treated for a psychiatric or emotional disorder. Nearly 40% drank more than 36 units of alcohol a week, and 14% had received treatment or consulted a doctor for alcohol-related problems. Heavy-drinking partners and multi-impulsive bulimics sought out each other. A quarter of partners had themselves been raised in a nuclear family in which a member had received psychiatric treatment; 12% had had a mother or sister with an eating disorder. Thirty-seven per cent of patients used a 'safe man', their fear of being hurt stemming from low self-esteem and a general sense of 'failure', and for 11% the relationship was abusive. PMID- 1422615 TI - Factors associated with relapse among opiate addicts in an out-patient detoxification programme. AB - Relapse is a central problem in the treatment of addictive behaviour, and a specific problem in the out-patient treatment of the opiate withdrawal syndrome. This study investigated factors associated with relapse among 42 opiate addicts receiving out-patient detoxification treatment at a London drug-dependence clinic. All subjects completed a questionnaire about their social, psychological, and environmental circumstances in the week before interview, and were interviewed within the first two weeks of the programme. Forty per cent had lapsed to illicit heroin abuse within the previous week. Interpersonal factors and drug-related cues were associated with lapse to opiate use. Most subjects encountered a range of high-risk situations, such as regularly meeting other drug users and being offered drugs, and persistent negative mood states. PMID- 1422616 TI - Clomipramine versus phenelzine in obsessive-compulsive disorder. A controlled clinical trial. AB - A double-blind clinical trial of clomipramine versus phenelzine was carried out on 30 patients suffering from DSM-III obsessive-compulsive disorder. The study period was 12 weeks, and the maximum doses used (from the fifth week on) were 225 mg/day for clomipramine (14 patients) and 75 mg/day for phenelzine (12 patients); four patients dropped out. Obsessive symptoms improved significantly in both drug groups, but there was no significant difference between groups. Depressive symptoms improved before obsessive ones. PMID- 1422617 TI - Differential rates of psychiatric disorders in adults with Down's syndrome compared with other mentally handicapped adults. AB - The total number of adults with Down's syndrome living in Leicestershire, ascertained by widespread enquiry, was found to be 378. Of these, 371 were matched with adults with mental handicap due to other pathologies, on the basis of age, sex, and type of residence. Those with Down's syndrome were found to have a different spectrum of mental disorders from those without the syndrome. In particular, Down's syndrome patients were more likely to have been diagnosed as having depression and dementia; the controls were more likely to have been diagnosed as suffering from conduct disorder, personality disorder, or schizophrenia/paranoid state. The same proportion of each group had been given a diagnosis of autism. PMID- 1422618 TI - The effect of age and residential placement on adaptive behaviour of adults with Down's syndrome. AB - Through widespread enquiry, the population of adults with Down's syndrome (aged over 18 years) in Leicestershire was estimated at 376. For 315 of these (83.8%), the immediate carer was invited to complete the Adaptive Behavior Scale (ABS). Completed ABS assessments were obtained on 81.9% of the adult population with Down's syndrome in the county. Additional information concerning residential history was obtained. When the sample was divided into five cohorts on the basis of age when the ABS assessment took place, an exponential decline in ability was observed. Deterioration in most domains of the ABS achieved statistical significance in the cohort aged 50-59, and in all domains in those aged 60 and over. The deterioration in global skills in older cohorts was attributed to ageing (and thereby probably Alzheimer's disease). Institutional placement was associated with low scores in younger groups only. PMID- 1422619 TI - Psychotic illness in multiple sclerosis. A clinical and magnetic resonance imaging study. AB - Ten patients with multiple sclerosis (MS) and psychosis were assessed using the Present State Examination, and matched retrospectively with respect to age, disability, duration of symptoms, and disease type with 10 MS patients without psychosis. Both groups underwent MRI of the brain. There was a trend for the psychotic group to have a higher total lesion score, particularly around the periventricular areas. This reached statistical significance in the areas around the temporal horn. In all cases, neurological symptoms preceded the onset of psychosis. The psychotic group also had a later age of onset of psychosis than psychotic patients without brain disease. These results point to an aetiological association between the pathological process of MS and psychosis. PMID- 1422620 TI - Diagnoses are not diseases. AB - The psychiatric community seems determined to ground its medical legitimacy on principles that confuse diagnoses with disease. If mental illnesses are diseases of the CNS, they are diseases of the brain, not the mind. If mental illnesses are the names of (mis)behaviour, they are forms of behaviour, not diseases. Psychiatric metaphors have the same role in medicine as religious metaphors have in theology. Religion is, among other things, the institutionalised denial of a finite life. Psychiatry is, among other things, the institutionalised denial of the tragic nature of life: individuals who want to reject the reality of free will and responsibility can medicalise life, and entrust its management to health professionals. Psychiatrists have succeeded in persuading the scientific community, the courts, the media, and the general public that the conditions they call mental disorders are diseases, that is, phenomena independent of motivation or will. The more firmly psychiatrically based ideas take hold of the collective American mind, the more foolishness and injustice they generate. Long ago, the law makers agreed to let psychiatrists literalise the metaphor of mental illnesses. Thus, the Americans With Disabilities Act (AWDA), scheduled to be fully implemented by July 1992, covers claustrophobia, personality problems, and mental retardation, though unlike DSM-III-R it excludes kleptomania, pyromania, compulsive gambling, and transvestism. The literal language of psychiatry allows motivated actions to be called 'disease'. Other examples of behaviour for which psychiatrists have disease names, and which AWDA implicitly accepts as genuine diseases, include dysmorphophobia, multiple personality disorder, frotteurism, hypoactive sexual desire disorder, and fractitious disorder with physical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422621 TI - Puerperal affective psychosis: is there a case for lithium prophylaxis? AB - It is well known that women with a history of manic-depressive or puerperal affective psychosis are at particularly high risk of relapse in the puerperium. This paper describes the use of lithium given during or after pregnancy to women with a history of bipolar illness or puerperal affective psychosis. The rate of puerperal relapse in these subjects was compared with that in a similar group of women not on lithium. The significantly better outcome of the treatment group highlights the need for a prospective controlled trial looking at the effectiveness of lithium in minimising puerperal bipolar relapse. PMID- 1422622 TI - Obsessive-compulsive disorder and paraphilia in a monozygotic twin pair. AB - We report OCD and paraphilia in two male members of triplets (the two males being monozygotic twins), and discuss the possible aetiological factors for this previously unreported occurrence. We suggest that patients presenting with paraphilia should be examined for OCD and that a detailed sexual history should be obtained in all patients with OCD. PMID- 1422623 TI - A transsexual male with 47,XYY karyotype. AB - Transsexuals are usually found to have a normal chromosome complement. The literature to date documents four transsexuals with 47,XYY pattern. This paper reports a fertile male with major cell line of 47,XYY and a gender identity disorder. PMID- 1422624 TI - Hyperkinetic syndrome and disruptive early experiences. AB - Five children aged 8-10 years presenting to child psychiatric clinics with hyperkinetic syndrome and severe disruptive early experiences are described. At referral all had been living in stable families for a minimum of four years. Biological risk factors were absent. It is proposed that the disruption of early attachments resulted in ill-regulated search and exploratory behaviour and that this had a continuing effect on the children's ability to focus and control attention skills and motor behaviour. PMID- 1422625 TI - Verbally mediated childhood post-traumatic stress disorder. AB - This report chronicles the verbally mediated traumatisation and subsequent PTSD in an 11-year-old girl. Information obtained from parental interviews, academic transcripts, anecdotal teacher comments, structured and unstructured interviews, and standardised anxiety, depression, and misconduct scales was used to highlight the unique distress of the patient. PMID- 1422626 TI - The clinical efficacy of maintenance electroconvulsive therapy in a patient with a mild mental handicap. AB - A 32-year-old chronically relapsing depressed male patient with a mild mental handicap had tried different forms of pharmacotherapy which were either not tolerated or failed to prevent recurrences of episodes of psychotic depression. The use of maintenance ECT as the mainstay of the therapeutic regime led to a marked consistent clinical improvement. PMID- 1422627 TI - Delusional parasitosis: folie a deux and attempted murder of a family doctor. AB - A 58-year-old woman suffering from delusional parasitosis tried to kill her general practitioner. Her husband shared in her beliefs but lost all delusional conviction after she was compulsorily admitted to a special hospital. The case illustrates the intractable nature and potential dangerousness of some of these cases, and their affinity to paranoia. PMID- 1422628 TI - Schizophrenia following prenatal exposure to influenza epidemics between 1939 and 1960. PMID- 1422629 TI - Ventricle-brain ratio in schizophrenia. PMID- 1422630 TI - Cost-benefit analysis of the Daily Living Programme. PMID- 1422631 TI - Insight and illusion. PMID- 1422632 TI - ECT for young people. PMID- 1422633 TI - Community care and suicide. PMID- 1422634 TI - 5-HT2 receptors, hallucinations, and dementia. PMID- 1422635 TI - Clinical use of moclobemide in Kleine-Levin syndrome. PMID- 1422636 TI - Lay theories of schizophrenia. PMID- 1422637 TI - Probing dexfenfluramine. PMID- 1422638 TI - Longevity and Down's syndrome. PMID- 1422639 TI - Psychophysiological investigations of patients with unilateral symptoms in the hyperventilation syndrome. PMID- 1422640 TI - Neuroleptic malignant syndrome. PMID- 1422641 TI - Self videotaping during psychosis. PMID- 1422642 TI - Length of training, hostility and the martial arts: a comparison with other sporting groups. AB - Previous research has indicated that training in the martial arts leads to a reduction in levels of hostility. However, such research has only compared hostility within martial arts groups. The present research compares two martial arts groups and two other sporting groups on levels of assaultive, verbal and indirect hostility. Moderated multiple regression analyses revealed a significant interaction between length of training in the respondent's stated sport and whether that sport was a martial art in predicting assaultive and verbal hostility. The form of the interaction suggests that participation in the martial arts is associated, over time, with decreased feelings of assaultive and verbal hostility. PMID- 1422644 TI - Medical cover for 'The Open' golf championship. AB - A review of 10 years' provision of medical cover at a major golf championship is presented. The average consultation rate was approximately 1 in 200 of those attending of whom 3% required transfer to hospital, the majority to orthopaedic or general medical departments. Familiarity with acute resuscitation and musculoskeletal complaints is required of the medical attendants. The provision of physiotherapy and chiropody services is essential, especially for the participants' complaints, two-thirds of which affected the axial skeleton. Good communications and close liaison with the Chief Marshal, Police and Ambulance Services are vital. PMID- 1422643 TI - Aetiology of handball injuries: a case--control study. AB - This article presents the results of a case--control study regarding the background to handball injuries among players of 12 years and older. Data were collected by means of a written questionnaire on the nature, location and direct causes of the injuries as well as information on risk factors. Injured players (n = 130) are compared with non-injured players (n = 512). The response for the cases was 67% and for the controls 75%. These injuries are frequently located at the lower extremities (54% of injuries), especially the ankle, and the majority involve distortions (35%) and strains (26%). Players greater than 20 years have a significantly greater risk of injury than players less than 20 years (odds ratio 1.9). Several factors seem to increase the injury risk, although not significantly: having greater than 5 years experience, not doing stretching exercises and not wearing tape or bandages. Another factor, not wearing elbow protectors, appears to decrease the injury risk significantly. It is advisable to interpret the results of this study with some caution, as selection and information bias might have influenced the validity to some extent. Furthermore, the reliability of the data is limited due to the relatively small number of injured players in the study. Some guidelines for future studies are formulated. PMID- 1422645 TI - Kenyan team care at the Special Olympics--1991. AB - The Kenyan team that competed at the International Summer Special Olympics comprised 38 athletes (both men and women) selected from all competitors at the national championships. The team was examined and a physiological fitness test carried out. The results enabled the organizers to arrange for treatment of prevailing illnesses, and the training programme was adjusted to the athletes' level. This team was voted the best team of the month of July, having won 33 gold, three silver and two bronze medals. Sound medical care of athletes should be taken before and during competition. Such management should aim at minimizing injuries and enabling athletes to perform at their best. PMID- 1422646 TI - More ways than one to slip on a banana: unusual forms of water sport injuries. PMID- 1422647 TI - Controlled trial of an ankle support (Malleotrain) in acute ankle injuries. AB - A randomized, controlled parallel-group trial has assessed 14 days' use of a new ankle support (Malleotrain, Bauerfeind, Aldershot, UK) in 220 patients (118 Malleotrain, 102 control group) with acute ankle injuries. Self-assessed pain levels were significantly lower in the group using Malleotrain at the end of the trial (P less than 0.05), as were median times taken for reduction of symptom scores to 10% (P less than 0.05) and total analgesic consumption during the trial (P less than 0.05). Overall clinical assessment scores were significantly superior in the Malleotrain group (P less than 0.02). Of those patients who received Malleotrain, 112 of 116 patients who commented (95% of all Malleotrain treated patients) did so positively and only one patient stopped wearing the support during the trial. Malleotrain is acceptable to patients with acute ankle injuries and its use increases the rate of alleviation of symptoms. Its use should therefore be considered in the management of all such patients. PMID- 1422648 TI - Fell walking injuries in Cumbria: a review. AB - An analysis of injuries sustained during fell walking in Cumbria and seen at the West Cumberland Hospital over a 3-year period is presented. There were 90 patients, including 19 multiple injuries and four deaths. This report focuses attention on the seriousness and magnitude of injuries associated with a pastime often thought to be harmless and risk-free. PMID- 1422649 TI - Mood, mileage and the menstrual cycle. AB - Forty women took part in a study to determine the effects of high-intensity training and the menstrual cycle on mood states. Half of the sample were competitive distance runners following a training load of between 50 km and 130 km running per week. Seven athletes were amenorrhoeic and 13 either eumenorrhoeic or oligomenorrhoeic. The remaining 20 subjects were inactive women who menstruated regularly. The mean age of all 40 subjects was 29 years. Each subject completed two identical Profile of Mood States (POMS) questionnaires. The 33 menstruating subjects completed both a premenstrual and a midcycle form and the amenorrhoeic athletes completed the questionnaires at a 3-week interval, which acted as a control for the potential effects of premenstrual syndrome (PMS) among the menstruating females. Results showed highly significant differences in mood profiles among amenorrhoeic athletes, non-amenorrhoeic athletes and inactive women. The greatest difference was between premenstrual and midcycle measures for the inactive group. PMS appears to cause marked negative mood swings among menstruating women which the POMS inventory is sensitive in detecting. While the lower-intensity-training runners appeared to benefit psychologically from a training distance of approximately 50 km week-1, high-intensity training had an adverse effect on mood. PMID- 1422650 TI - Muscle power predicts freestyle swimming performance. AB - The purpose of this study was to determine the relationship between non-invasive laboratory measures of 'muscle power' and swim performance over sprint (50 m) and middle-distance (400 m) events. Twenty-two swimmers performed an upper and lower body Wingate Anaerobic Test (WAT) and a maximal sustained power output test (MPO) for the upper body. Peak power (PP) and mean power (MP) were determined for the WAT, while peak sustained workload (WLpeak) was determined for the MPO. Timed swims over 50 m and 400 m were undertaken by all swimmers during which the number of arm strokes per length was recorded. Highly significant relationships were found between sprint-swim speed (S50) and mean power of the arms (MP(arms)) (r = 0.63, P less than 0.01), between S50 and mean power of the legs (MP(legs)) (r = 0.76, P less than 0.001) and between S50 and the distance covered with each arm stroke (DS) (r = 0.91, P less than 0.001). Multiple regression analyses revealed that WAT power indices for the legs did not significantly increase explained variance in S50 above that of the arms. The relationship between WL(peak) and S400 was highly significant (r = 0.70, P less than 0.001) and indicates the importance of arm power in the longer distance swim events. PMID- 1422651 TI - Bulimia nervosa symptomatology and body image disturbance associated with distance running and weight loss. AB - To investigate the hypothesis that problems characteristic of eating disorders may often be associated with distance running, 20 women who had lost weight through distance running were compared with a control group who did not exercise and had not lost weight and a comparison group of bulimia nervosa patients. Dependent variables were measures of depression, bulimia nervosa symptomatology, and body image disturbance. No differences were found between the runner group and the normal controls. Bulimics differed from runners and controls on most measures. Thus, the results did not support the proposition that weight loss through running leads to problems related to eating and body image. The failure to find disturbances in body image in runners suggests that body image disturbances are not a direct result of weight loss, as suggested by some theorists. PMID- 1422652 TI - Altitude-dependent changes of directional hearing in mountaineers. AB - This study demonstrates apparent deterioration in the ability to localize sound associated with acute exposure to high altitude in ten subjects on three mountaineering expeditions. Furthermore, the auditory localization errors improved to sea level values after a period of acclimatization. Occurring at altitudes where overt neurological symptoms are not usually seen, impairment of sensory perception may explain the increase in accidental deaths associated with altitude exposure due to disorientation and misjudgment but before hypoxia is evident. PMID- 1422654 TI - Society of Apothecaries diploma in sports medicine. AB - The Society of Apothecaries examination in Sports Medicine consists of four parts: a multiple-choice question paper; a written paper; a clinical section; and an oral section. The candidates must have experience in sports medicine and have to submit a dissertation and a case history book. The importance of an examination in sports medicine is discussed. PMID- 1422653 TI - Potential markers of heavy training in highly trained distance runners. AB - Markers of a heavy increase in training were examined in ten highly trained distance runners (mean(s.d.) age 29.8(1.7) years, maximal oxygen intake 65.3 ml kg-1 min-1, personal best 10-km time 31 min 4 s) who undertook a deliberate 38% increment of training over a 3-week period. Their running performance did not improve, and six of the ten subjects developed sustained fatigue, suggesting that training was excessive, although the full clinical picture of overtraining did not develop. The Profile of Mood States was the best single marker of disturbed function, indicating increased fatigue and decreased vigour. There were no useful changes of resting heart rate or perceived exertion during submaximal running, sleep was undisturbed, and there were no orthopaedic injuries. Two subjects developed rhinoviral infections following the heavy training, and a third complained of symptoms that were diagnosed 2 weeks later as exercise-induced asthma. The increase of serum cortisol normally induced by 30 min of submaximal exercise was no longer seen when the same acute exercise was performed after heavy training. Resting lymphocyte proliferation tended to increase in response to phytohaematoglutinin (PHA) and concanavalin A (Con A), the ratio of helper to suppressor cells (H/S) decreased, and pokeweed mitogen induced smaller increases in IgG and IgM synthesis. Whereas before heavy training, PHA-stimulated lymphocyte proliferation was unchanged by 30 min of acute submaximal exercise, after 3 weeks of heavy training the same bout of exercise caused an 18% suppression of proliferation. Likewise, heavy training brought about a decrease of T-lymphocytes in response to acute submaximal exercise, but an abolition of the acute exercise-induced decrease in the H/S ratio. The previously observed exercise-induced decrease of IgG synthesis did not occur when the same acute bout of exercise was performed after heavy training. We conclude that such minor and transient changes of immune function may possibly be a warning that training is becoming excessive, but they have only a limited significance for overall immune function. PMID- 1422655 TI - Appearances of choroidal osteomas with diagnostic imaging. AB - The diagnostic imaging appearances of three choroidal osteomas (osseous choristomas) are presented. This rare, benign choroidal tumour is being recognized with increasing frequency, and is important to remember in the differential diagnosis of any unusual mass in the ocular fundus lest it be mistaken for a more sinister lesion. All three osteomas were demonstrated by ocular ultrasound (US), fluorescein angiography (FA) and computed tomography (CT) but none by plain radiography. None of the lesions was visible on magnetic resonance imaging (MRI); the reason for this is probably the bony nature of the tumours. The appearances of choroidal osteomas on US, FA, plain radiography and CT are discussed. To our knowledge this is the first report of a series of choroidal osteomas investigated by MR. PMID- 1422656 TI - The role of hysterosalpingography in modern gynaecological practice. AB - A retrospective review of hysterosalpingography (HSG) in a major gynaecological centre was carried out. 324 patients attended (95%) for HSG out of 341 patients referred for this investigation. 189 examinations (58.3%) were abnormal. The requests and radiological findings were reviewed and the results compared with laparoscopy. HSG remains an integral part of gynaecological investigation and its value has not diminished in modern practice. PMID- 1422657 TI - Portable chest radiography in intensive care: a comparison of computed and conventional radiography. AB - A prospective study was performed comparing computed and conventional radiography for the detection and visibility of cardiovascular devices in intensive care unit patients. Computed images were obtained using a commercially available 2K x 2K, 12-bit storage phosphor plate system. Image sets from 50 patients were assessed independently by three observers. A significant difference between the types of image was found for the detection of mediastinal drainage tubes and prosthetic valves. Computed images allowed greater confidence in the identification of courses and tips of lines. This advantage was most marked with edge-enhanced computed images. PMID- 1422658 TI - Doppler ultrasound scanning in the detection of renal artery stenosis in hypertensive patients. AB - The diagnostic accuracy of Doppler ultrasound in the detection of renal arterial disease has been assessed in a prospective study of 61 hypertensive patients. The findings of Doppler ultrasound were compared with the results of renal angiography. In 15 patients (24.5%) no accurate Doppler signs could be obtained and the Doppler ultrasound examination was considered a technical failure. Of the remaining 46 patients, 24 had renal artery stenosis. Nine of the stenoses were not detected by Doppler ultrasound and in three patients a false positive diagnosis of renal artery stenosis was made. The sensitivity of Doppler ultrasound was 62.5%, the specificity 86.4% and the overall diagnostic accuracy was 73.9%. By comparing the 15 patients in whom Doppler ultrasound failed with the 46 in whom it was successful, age appeared to be higher and creatinine clearance lower in the failure group. By comparing the 34 patients with true positive and true negative results with the 12 patients with false results, no significant differences were found. In a multivariate analysis, higher age showed a significant relation to failure of Doppler ultrasound. Doppler ultrasound has limited value in the screening of hypertensive patients for renal artery stenosis. PMID- 1422659 TI - Localized loss of the infrabronchial descending aortic interface as a normal variant. AB - Localized loss of the aortic interface may occur as a normal variant or may be due to an adjacent mass or opacification. The former category is divided into four types depending on position and length of loss of interface. The findings on conventional chest radiographs are correlated with computed tomographic findings. PMID- 1422660 TI - Pelvic phleboliths: is there an association with diverticulitis? AB - Pelvic phleboliths are familiar structures to radiologists although their pathogenesis is not fully understood. The literature suggests a relationship between the prevalence of phleboliths and diverticular disease, and with a low fibre diet. Phleboliths are said to be seen more frequently in women and on the left side in the pelvis. Their number seems to increase with advancing age. We have attempted to establish relations of phleboliths with diverticulitis, diverticulosis, sex, age and pelvic location. In this study the only statistically significant relation was an increase of the number of phleboliths with advancing age. PMID- 1422661 TI - A figure of merit for the assessment of image intensifier systems. AB - A dimensionless figure of merit (F), which combines key aspects of the performance of image intensifier systems, is derived. This figure is ideally independent of input air kerma rate and field size and relates to the fundamental characteristics of the image reception chain. In practice it is calculated from measurements of the threshold contrast (noise) and limiting resolution using the Leeds test objects and the input air kerma rate. Several practical examples illustrate its usefulness in simple performance assessment and quality assurance procedures. A comparison is made with the use of detection index diagrams. PMID- 1422662 TI - Radial diffusion coefficient mapping. AB - The two-dimensional mapping of the effective diffusion coefficient of water in tissues may provide a useful method of tissue characterization to complement T1 and T2 relaxation time studies for diagnostic purposes. Current diffusion techniques rely on the application of large gradient strengths and long echo times to achieve the required sensitivity. This, in turn, limits the applicability of the technique to tissues having long T2s with rapid water diffusion. In addition, the inherent directionality of these methods results in only the partial encoding of diffusion information. A modified diffusion sequence is presented, radial diffusion mapping (RAD), which provides enhanced sensitivity diffusion maps by employing gradient sensitization in three orthogonal directions. Results in both phantoms and volunteers are presented, together with an investigation of the effects of T2 on the measurement accuracy. Using RAD, a two- to five-fold improvement in sensitivity was achieved, thus significantly enhancing the dynamic range of the method and allowing more accurate in vivo diffusion measurements to be carried out. PMID- 1422663 TI - Impact of hydration status on body composition as measured by dual energy X-ray absorptiometry in normal volunteers and patients on haemodialysis. AB - To evaluate the influence of hydration status on the estimation of body composition using dual-energy X-ray absorptiometry (DXA), six normal volunteers and seven patients on maintenance haemodialysis were investigated using two different DXA machines (Lunar DPX, Hologic QDR 1000/W). Normal volunteers were studied (Hologic QDR 1000/W) before and 1 h after ingestion of breakfast, lunch and dinner (drinking various amounts of liquids at each meal, 0.5-2.4 kg). Whereas bone mineral content and body fat mass did not change, lean body mass of the trunk increased as a consequence of the meals. Conversely in patients on haemodialysis (Lunar DPX), lean body mass decreased in all segments of the body as a consequence of removal of 0.9-4.4 kg of salt-containing fluid by haemodialysis (trunk 61%, legs 30%, arms 5.5% and rest of the body 3.5%), whereas bone mineral content and body fat mass remained unchanged. However, this finding(s) did not hold true in one particular patient with bilateral hip prostheses. Measurement of body composition in eight normal volunteers on the same day with both machines showed similar results for lean and fat mass, whereas bone mineral content was found to be 17% higher using the Lunar DPX. In summary, in centres where both machines are available, follow-up of one individual patient should always be performed using the same equipment. In addition, hydration status and food intake must be taken into account when repetitive measurements of lean body mass are performed in the same patient. PMID- 1422664 TI - Single- versus dual-energy quantitative computed tomography for spinal densitometry in patients with rheumatoid arthritis. AB - Lumbar bone mineral density was measured by both single- and dual-energy quantitative computed tomography in 109 patients with rheumatoid arthritis. The results were corrected for the age-related increase in vertebral fat content by converting them to percentages of expected densities, using sex and energy-level specific regression equations obtained in a normal reference population. The percentages of expected density are approximately 10% lower in the single- than in the dual-energy mode, both in the patients with and without prednisone therapy. This difference is statistically highly significant, and is positively correlated with the duration of the disease and with the degree of radiological joint destruction. The data suggest that the vertebral fat content may be increased in patients with rheumatoid arthritis, as a consequence of disease dependent mechanisms. PMID- 1422665 TI - Efficacy of low-dose iodine-131 ablation of post-operative thyroid remnants: a study of 69 cases. AB - Low-dose iodine-131 of mean activity 1117 MBq was used to ablate post-operative thyroid remnants in 69 patients with differentiated thyroid cancer. Successful ablation was defined as uptake of less than 1% at 48 h and absence of visible image on the post-ablation scan. Ablation by one dose was successful in 95% of patients after total or subtotal thyroidectomy, and 56% of patients after partial or hemithyroidectomy. All patients with uptake of 10% or less on the pre-ablation scan had successful ablation. The results are compared with other reports using low-dose radioiodine ablation and the significance of the findings discussed. PMID- 1422666 TI - Functional changes in the pig kidney following irradiation with fractionated doses of fast neutrons (42 MeVd-->Be). AB - The right kidney of female Large White pigs, approximately 14 weeks old, was irradiated with fractionated doses of fast neutrons (42 MeVd-->Be). The total doses used were 6.6-9.2 Gy. Changes in kidney function, assessed as the functional index (FI, where FI = irradiated kidney function/unirradiated kidney function) or as individual kidney glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), were serially determined up to 104 weeks after irradiation using 99Tcm-DTPA and 131I-hippuran renography. The animals were then euthanized, the kidneys removed and weighed. A dose-dependent reduction in FI was seen within 13 weeks of irradiation. Measuring individual kidney function revealed a hyperaemic response in both irradiated and unirradiated kidney 4 weeks after irradiation. This was followed by a dose-dependent reduction in irradiated kidney GFR and particularly ERPF. The ED50 value for the impairment in ERPF, assessed as the percentage of irradiated kidneys exhibiting a > or = 50% reduction in ERPF, was significantly lower than that for GFR, i.e. 7.20 +/- 0.10 Gy compared with 8.44 +/- 0.07 Gy (p < 0.001). A dose-related reduction in irradiated kidney weight was also observed. These fast neutron-induced changes in renal function and weight are qualitatively similar to those observed following photon irradiation of the pig kidney. PMID- 1422667 TI - Retrospective analysis of nasopharyngeal carcinoma treated during 1976-1985: late complications following megavoltage irradiation. AB - A retrospective analysis was undertaken of the late complications observed in 4527 patients with nasopharyngeal carcinoma treated by megavoltage radiotherapy during the years 1976-1985. Unconventional fractionation schedules were used because of serious resource limitations. The median equivalent doses were 65 Gy to the nasopharyngeal region and 53 Gy to the cervical region. 707 patients had reirradiation for local recurrences and 250 for regional relapses. The 10-year actuarial cancer-specific survival was 47%, and the corresponding all complication-free and neurological-complication-free rates were 40% and 72%, respectively. Altogether, 1395 (31%) patients developed one or more late irradiation sequelae. The majority were mild soft-tissue damages, but 322 (7%) had significant functional disturbances, from which 62 (1%) died. Neurological damage that occurred in 450 (10%) patients constituted the major morbidity and accounted for all but three of the treatment mortalities. The cumulative incidence of the various complications is summarized, and the data recorded in the literature reviewed in order to give a proper perspective of the problem. Patients treated during 1981-1985 had a significantly higher actuarial encephalomyelopathy-free rate than those treated during 1976-1980, but the incidence-free rates for the other neurological complications remained unimproved, suggesting that the improvement could be mainly attributed to additional shielding for the brainstem rather than the reduction of dose from 3.8 4.2 Gy to 2.5 Gy per fraction. PMID- 1422668 TI - Localization of impalpable breast lesions using the Hawkins needle. PMID- 1422669 TI - Second malignant neoplasm following treatment of Hodgkin's disease: a case report. PMID- 1422670 TI - Extradural paraganglioma with multiple skeletal metastases. PMID- 1422671 TI - Intrathoracic lymphadenopathy and HIV infection. PMID- 1422672 TI - Basal cell carcinomas do metastasize. PMID- 1422673 TI - A curious case of pelvic calcification. PMID- 1422674 TI - Visualization of the axillary vein during 99Tcm methoxy-isobutyl-isonitrile (MIBI) myocardial imaging. PMID- 1422675 TI - Radiation protection associated with well woman screening. PMID- 1422676 TI - Radiation protection associated with well woman breast cancer screening. PMID- 1422677 TI - Standards of radiation protection in mammographic screening. PMID- 1422678 TI - Radiation protection associated with well women breast cancer screening. PMID- 1422679 TI - Haemostasis in urology: mechanism and pharmacology. PMID- 1422680 TI - Acquired cystic disease of the kidney and renal carcinoma in haemodialysis patients: ultrasonographic evaluation. AB - Ultrasonography was performed in 661 dialysis patients and acquired cystic disease of the kidney was found in 156 (125 men and 31 women). A higher incidence of cystic disease was found in males. There was no significant difference between the patients with and those without acquired cystic disease in terms of average age, but the duration of haemodialysis in those with acquired cystic disease was significantly longer. There was an increased incidence of cystic disease in patients with glomerulonephritis and the duration of haemodialysis in these patients was significantly longer. This suggests that the increased incidence of acquired cystic disease of the kidneys in the patients with glomerulonephritis is simply related to the longer duration of treatment. Twelve patients with renal carcinoma were found in this study. The average age at diagnosis of renal carcinoma was not significantly different between the patients with and those without acquired cystic disease, but the duration of dialysis was significantly longer in renal carcinoma patients with acquired cystic disease. The incidence of renal carcinoma in dialysis patients with acquired cystic disease was 3.85% and in those without it was 1.19%. These rates are considerably higher than those found in the general population and indicate that the risk of renal carcinoma is higher in dialysis patients both with and without acquired cystic disease. PMID- 1422681 TI - Agglomeration of calcium oxalate monohydrate in synthetic urine. AB - The development of agglomerated particles of calcium oxalate monohydrate (COM) on the semi-batch precipitation from a synthetic urine carried out at physiological conditions (37 degrees C, pH = 5.5) was studied by optical and electron scanning microscopy. COM agglomerates develop by primary and secondary agglomeration proceeding simultaneously; the latter mechanism is, however, less important than the former. Citrate ions modify slightly the COM crystal shape and inhibit primary agglomeration. Mucin particles serve as a substrate for preferential formation (nucleation) of new COM crystals. The structure of formed agglomerates closely resembles that of a certain type of COM renal calculi. A combination of primary agglomeration of crystals forming stones and nucleation of new crystals on a mucoprotein layer partially covering their surface constitutes the possible mechanism of such stone development. Experimental data support this mechanism. PMID- 1422683 TI - Management of impacted upper ureteric calculi: results of lithotripsy and percutaneous litholapaxy. AB - Despite the availability of lithotripsy and endourology, clear guidelines on the management of impacted upper ureteric calculi are lacking. In this study, 51 upper ureteric calculi treated with in situ extracorporeal shock wave lithotripsy (ESWL) were classified according to the degree of impaction as indicated by proximal back pressure changes. Patients with mild proximal hydronephrosis (or none at all) had a success rate of 93% but only 35% of those in the impacted group (moderate to severe hydronephrosis) had a successful outcome. A percutaneous antegrade approach to 29 impacted upper ureteric calculi resulted in total clearance in 23 cases; 4 other patients were rendered stone-free following additional procedures, an overall success rate of 93%. The only complication was a ureteric stricture in 1 patient. We recommend the percutaneous approach in the management of impacted upper ureteric calculi. PMID- 1422682 TI - Urological complications following live donor kidney transplantation: effect of urinary schistosomiasis. AB - Urological complications were studied in 310 live donor kidney transplants. All recipients and donors were investigated for urinary schistosomiasis by examining tissue obtained intra-operatively from the donor's ureter or the patient's bladder. Schistosomiasis was histologically documented in 76 cases (patient's bladder (46), donor's ureter (9), both (21)). The incidence of urological complications was 11/76 (15%) in the schistosomal group and 14/234 (6%) in the non-schistosomal group; this was statistically significant. Among the schistosomal patients, the site of infestation had no statistically significant effect on the incidence of urological complications. No deaths or graft losses were directly attributable either to these complications or to their surgical correction. PMID- 1422684 TI - Management of hydatid cysts of the urinary tract. AB - Eleven patients with hydatid disease of the urinary tract have been seen in the last 5 years. Seven patients had cysts of the kidneys and 4 had large retrovesical hydatids. Seven of the 8 patients with renal hydatids presented with loin pain and mass. Three patients with renal communicating hydatids also presented with haematuria which was due to passing "grape skin" (hydatid membrane) in the urine. Two patients with retrovesical hydatids had bladder outflow obstruction and 2 had bilateral ureteric obstruction leading to uraemia. Eight of 11 patients had associated hydatids of other organs such as the liver (4 patients), peritoneal cavity (2) and lungs (1). Computed tomography was the most useful and specific investigation. In both renal and pelvic (retrovesical) hydatid cysts, endocystectomy with either partial excision or plication of the ectocyst is the standard treatment. In renal communicating hydatids the options are either nephrectomy (partial or total) or endocystectomy with closure of the communication. The use of cryocone and scolicidal agents is mandatory during surgery. PMID- 1422685 TI - The actions of extracellular magnesium on isolated human detrusor muscle function. AB - The effects of increasing the extracellular magnesium concentration ([Mg]) on the in vitro mechanical and electrophysiological properties of isolated human detrusor smooth muscle have been investigated. Raising extracellular Mg reduced the magnitude of the electrically-induced phasic contractions as well as spontaneous contractions. A similar increase in the [Mg] reduced the magnitude of the inward Ca2+ current associated with the action potential as well as shifting the activation curve to more positive potentials. Spontaneous oscillations of intracellular Ca2+ could be observed in some isolated cells and such activity was also abolished by raising the extracellular [Mg]. It is proposed that the contractile effects of raised extracellular Mg are mediated by an action on the inward Ca2+ current and that these observations suggest a means whereby normal and abnormal detrusor contractions might be effectively regulated. PMID- 1422686 TI - Vesica fellea--a new substitute for the bladder? An experimental study. AB - The urinary bladders of 8 dogs were removed and replaced with their own gallbladders using microvascular anastomoses. Post-operative assessment included measurement of blood urea nitrogen (BUN) and creatinine (Cr), intravenous urography and histological examination of the autotransplanted gallbladders. The neobladders proved to be good reservoirs without urinary leakage. Renal function was well preserved in 6 dogs; post-operative BUN and Cr levels were raised in 2 dogs and the concentrating ability of the kidneys was reduced. The neobladders were perfect histologically. PMID- 1422688 TI - Laparoscopic pelvic lymph node dissection. AB - The infiltration of pelvic lymph nodes by carcinoma of the prostate or carcinoma of the bladder is an important factor in disease staging. Until now, this could be accurately assessed only by means of open surgery, an undesirable option as an investigation. Recent advances in laparoscopic instruments and camera systems have allowed the performance of laparoscopic pelvic lymph node dissection. A series of dissections in 14 patients is reported. PMID- 1422687 TI - Outcome in carcinoma in situ of bladder treated with intravesical bacille Calmette-Guerin. AB - Fifty-three patients with carcinoma in situ of the bladder were treated with Evans strain BCG given intravesically. Complete remission was achieved after either one or two 6-weekly courses in 53% of patients. The median duration of remission was 32 months. Treatment-related bladder symptoms were minor during the first course, more severe during the second. There was no relation between severity of symptoms and likelihood of response. With a median follow-up of 32 months, disease progression has occurred in 10% of complete responders, whereas failure to respond on either cystoscopic, histological or cytological grounds was associated with a 48% progression rate. Although intravesical BCG produces impressive responses in carcinoma in situ of the bladder, managed conservatively the condition remains a dangerous one. PMID- 1422689 TI - Treatment of advanced localised prostatic cancer by orchiectomy, radiotherapy, or combined treatment. A Medical Research Council Study. Urological Cancer Working Party--Subgroup on Prostatic Cancer. AB - A total of 277 patients with apparently localised prostatic cancer (T2-T4 NXMO) were allocated at random to receive radiotherapy alone (88), orchiectomy alone (90) and combined therapy (99) between 1980 and 1985. The main outcome measures were survival, time to appearance of metastases and treatment of local disease progression by further transurethral resection. Orchiectomy, whether alone or with radiotherapy, produced a significant delay in detection of metastases when compared with radiotherapy alone. There were no statistically significant differences between the 3 treatment groups in local disease control or in overall survival. PMID- 1422690 TI - Prostate cancer--the impact of irradiation on urinary outlet obstruction. AB - A series of 245 patients with prostate cancer treated by external irradiation was analysed to assess the impact of irradiation on urinary outlet obstruction. Prior to irradiation, obstruction was observed in 147/245 patients (60%). Irradiation either with or without hormonal therapy was as efficacious as transurethral resection of the prostate (TURP) in alleviating obstructive symptoms; 14/16 patients treated by irradiation alone responded, as did 19/19 who received hormonal therapy and irradiation and 109/112 who underwent TURP and irradiation. Following irradiation, 41/245 patients developed post-irradiation obstruction, 26/213 had post-irradiation strictures and 15/32 developed recurrent cancer. Surgical intervention was required less often for the management of recurrent obstruction caused by stricture as compared with recurrent cancer. TURP and urinary outlet obstruction acted as independent and additive variables to the development of post-irradiation stricture. Thus the avoidance of TURP in patients with obstructive symptoms reduced but did not eliminate the risk of developing a stricture. PMID- 1422691 TI - Screening for bacteriuria in urological patients using reagent strips. AB - A rapid and accurate ward-based method of diagnosing urinary infection would be of value in determining the prescription of antibiotics in pre-operative urological patients. This study describes the sensitivity and specificity of a screening technique based on commercially available reagent strips in the diagnosis of urinary infection. A total of 222 pre-operative samples and 83 post operative samples was studied to compare the results of formal urine culture and reagent strips. Using a definition of a positive nitrite or a positive leucocyte esterase on the reagent strips as being suggestive of infection, it was found that the strips had a sensitivity of 91% and a specificity of 85% compared with formal culture in pre-operative samples. The results from post-operative samples were less satisfactory, the strips having a sensitivity of only 71% and specificity of 55%. The strips were insensitive but specific in the identification of pyuria in pre-operative specimens. These results suggest that reagent strips can be used as a ward-based method to identify men at risk of infection before urological procedures, and may allow selectivity in the use of peri-operative antibiotics. PMID- 1422692 TI - Natural history of obstructed and pseudo-obstructed megaureters detected by prenatal ultrasonography. AB - In a series of 38 patients with non-refluxing megaureters detected by prenatal ultrasonography, 89% were males and 16% had associated ipsilateral or contralateral urinary anomalies. By renographic criteria, 36% of ureters were not obstructed; renal function was never impaired initially and, on follow-up, spontaneous resolution of dilatation was common. Infective urinary calculi developed in 3 of the boys. In ureters obstructed by renographic or pressure perfusion criteria, 79% exhibited normal renal function initially. Most such patients were managed expectantly; on follow-up, functional deterioration occurred in 2 patients, while in the remainder dilatation usually persists but without change in function. PMID- 1422693 TI - Unusual presentation of adult posterior urethral valve. PMID- 1422694 TI - Pelvic lipomatosis or pericystitis plastica? PMID- 1422695 TI - Mesothelioma of the tunica vaginalis of the testis. PMID- 1422696 TI - Ureteric-anal canal fistula secondary to ureteric calculus. PMID- 1422697 TI - Leiomyoma of the renal pelvis. PMID- 1422698 TI - Ureterocolic fistula due to impacted ureteric stone. PMID- 1422699 TI - Choriocarcinoma arising in transitional cell carcinoma of the bladder. PMID- 1422700 TI - Re: Effect of catheter material on the incidence of urethral strictures. PMID- 1422701 TI - Re: Idiopathic kidney stone formation--where and why? PMID- 1422702 TI - Re: Chronic testicular pain following vasectomy. PMID- 1422703 TI - Re: Conservative treatment of vesicovaginal fistulas by bladder drainage alone. PMID- 1422704 TI - Re: Cavernous haemangioma of the glans penis. PMID- 1422705 TI - Re: Ethics, logistics and a trial of transurethral versus open prostatectomy. PMID- 1422706 TI - The electronic information revolution and how to exploit it. AB - Medical information is increasingly stored in electronic format, enabling faster and more flexible access to the literature. Online, compact disc and floppy disc databases are widely available. The origins and development of these different database media are described. The strengths and weaknesses of each, and the ways in which they complement each other, are examined. Ease of access to medical information can result in data management problems; the role of bibliographic software in ensuring full exploitation of the electronic information revolution is therefore emphasized. PMID- 1422707 TI - Iliofemoral versus femorofemoral bypass: a 6-year audit. AB - Iliofemoral and femorofemoral crossover bypass operations performed over a 6-year period were reviewed. A total of 226 patients underwent 231 operations from 1984 to 1990. Seventy-two patients had 75 iliofemoral grafts and 154 patients had 156 femorofemoral grafts. The early mortality rate was 6 per cent for the iliofemoral group and 1.3 per cent for femorofemoral reconstruction. There was a higher reoperation rate in the iliofemoral group (31 versus 16.0 per cent). The cumulative patency rate at 6 years was 75 per cent for iliofemoral bypass and 92 per cent for the femorofemoral procedure (P < 0.01), while the survival rates for the same period were 55 and 74 per cent respectively (P < 0.01). Hospital stay was significantly shorter for patients undergoing femorofemoral bypass (P < 0.05). PMID- 1422708 TI - Synchronous aortic and gastrointestinal surgery. AB - The synchronous performance of aortic and gastrointestinal surgery may hold an increased risk of aortic graft infection. The experience of one surgeon who performed 32 such synchronous operations over a period of 11 years is reviewed. No graft infection occurred and it is concluded that such combined operations may be safer to perform than staged surgery in elderly patients. PMID- 1422709 TI - Vein compliance: a preoperative indicator of vein morphology and of veins at risk of vascular graft stenosis. AB - Compliance measurements of 53 long saphenous veins before femorodistal bypass have been performed using a duplex scanner with venous occlusion for distension. These have been compared with the histological features of the veins. There was significantly more moderate or severe focal hyperplasia and circular muscle hypertrophy in distal long saphenous vein than in its proximal counterpart (P < 0.01 and P < 0.05 respectively). The mean (95 per cent confidence interval) compliance of distal vein with moderate or severe hyperplasia was 0.16 (0.13 0.19) compared with 0.29 (0.22-0.36) for that with no, minimal or mild hyperplasia (P = 0.001). The mean compliance of distal vein with moderate or severe muscle hypertrophy was 0.19 (0.17-0.21) and of vein with no, minimal or mild hypertrophy 0.25 (0.21-0.29) (P = 0.14). The mean lowest compliance in seven patients who developed stenosis was 0.10 (0.07-0.13) compared with 0.21 (0.16 0.26) in the rest (P < 0.001). Preoperative measurement of vein compliance can be used to identify vein with marked pre-existing intimal hyperplasia and as a predictor of future graft stenosis. PMID- 1422710 TI - Risk of rupture of postangiographic femoral false aneurysm. AB - The surgical management of 50 false aneurysms caused by transfemoral arterial catheterization was reviewed to document the incidence and effects of rupture before repair. Twelve false aneurysms ruptured, leading to shock in six patients, distal ischaemia in three and stroke in one. The mean(s.d.) time from catheterization to rupture was 2.8(1.7) (range 1-6) days. Postoperative complications occurred in seven patients with ruptured and eight with non ruptured aneurysms (P < 0.04). The mean(s.d.) age of patients with ruptured aneurysms was 67.2(6.3) (95 per cent confidence interval 63.5-70.8) years and those without 58.5(9.1) (95 per cent confidence interval 55.3-61.7) years (P < 0.008). On multiple regression analysis, age, peripheral vascular disease and raised plasma liver enzyme levels on admission were found to be significant independent predictive variables for rupture (all P < 0.05). It is recommended that patients with these risk factors undergo urgent operative correction of femoral false aneurysm. PMID- 1422711 TI - Reperfusion injury in skeletal muscle: a prospective study in patients with acute limb ischaemia and claudicants treated by revascularization. AB - A study was carried out to document the occurrence of rhabdomyolysis and renal complications in patients undergoing vascular reconstruction. Indices of muscle damage and renal function were monitored before, during and for up to 10 days after vascular reconstruction for a variety of conditions ranging from intermittent claudication to acute ischaemia. Seven patients with acute limb ischaemia (group 1) and nine with intermittent claudication (group 2) were studied prospectively. In group 1, median creatine kinase (CK) and myoglobin levels were markedly raised 24-48 h after surgery (CK, 29,370 units/l; myoglobin, 8.17 mg/l). Myoglobin reached its peak concentration and declined more quickly than CK, but both indices gave similar information about the extent of muscle damage. In contrast, patients undergoing elective surgery for claudication showed no significant departure from reference values for myoglobin or CK. All patients in group 1 underwent fasciotomy to relieve raised compartmental pressures and five were treated with alkali and mannitol to produce diuresis. Despite these measures, two patients suffered renal failure (peak creatinine levels 611 and 590 mumol/l) after successful revascularization and subsequently required haemodialysis; these patients did not have diuresis. One of these patients died following a stroke 8 days after surgery; the other survived and was discharged with a normal limb and restored renal function. There was no evidence of muscle damage or renal complications in group 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422712 TI - Colour-coded duplex ultrasonography in the selection of patients for endovascular surgery. AB - Endovascular surgery using angioplasty or atherectomy may potentially relieve the symptoms of claudicants with minimal morbidity, but results are best when short stenoses are treated. In this study, colour-coded duplex ultrasonography has been compared with angiography. In aortoiliac segments duplex examination had a sensitivity of 88 per cent and a specificity of 100 per cent; in femoropopliteal disease the sensitivity was 100 per cent and duplex scanning identified more disease than angiography. Subsequently, 73 symptomatic limbs with femoropopliteal disease were scanned to assess their suitability for endovascular surgery. Of these limbs, 27 (37 per cent) had suitable lesions and the remaining 46 (63 per cent) were spared angiography. Colour-coded duplex ultrasonography can reliably be used to select patients for endovascular surgery. PMID- 1422713 TI - Prevalence of lower limb ulceration in an urban health district. AB - Before establishing a community leg ulcer programme, a survey was performed to assess the incidence and prevalence of lower limb ulceration in the Newcastle Health District. The prevalence was 1.9 per 1000 in patients over the age of 45 years, and the annual incidence 3.5 per 1000 in the same age group. Recurrent ulcers represented 47 per cent of the total and 50 per cent of all ulcers had been present for > 6 months. District nurses spent 190 h per week in the community dressing leg ulcers, making a total number of 25,922 visits each year. In the treatment of leg ulcers 35 different types of dressing were used and only 14 per cent of ulcerated limbs were treated by appropriate compression. Of all patients with leg ulcers, 35 per cent had been seen by a hospital specialist but only 7 per cent had been examined by a vascular surgeon at any time. PMID- 1422714 TI - Role of topical lignocaine during carotid endarterectomy. AB - Forty carotid endarterectomies were undertaken in 34 patients. Operations were prospectively randomized to periarterial application of either 1 per cent lignocaine (n = 19) or normal saline (n = 21), and detailed measurements taken of intraoperative pulse rate and blood pressure. Patients receiving lignocaine demonstrated a lower pulse rate, and lower systolic and mean blood pressures than those receiving placebo, with significance in relation to clamp application and shunt removal (P < 0.05). It was particularly noticeable that patients receiving lignocaine demonstrated less intraoperative variation in pulse rate and blood pressure. Topical lignocaine stabilizes pulse rate and blood pressure during carotid endarterectomy. PMID- 1422715 TI - Needle core biopsy of the breast with a spring-loaded device. AB - Over a 2-year period, 151 outpatients with a palpable breast lump requiring needle core biopsy were randomized to a Tru-Cut 14-G (T14), Bioptycut 14-G (B14) or Bioptycut 18-G (B18) needle. Use of a Biopty gun resulted in less pain than a Tru-Cut needle. An inadequate sample was obtained after two needle passes in 11 of 49 (T14), none of 51 (B14) and two of 51 (B18) patients (chi 2 = 14.6, 2 d.f., P = 0.0007). Tissue samples were assessed by a single pathologist for tissue volume and overall diagnostic value; the B14 group scored better than the B18 and T14 for both of these parameters (P < 0.003). The sensitivities were 68 (T14), 88 (B14) and 96 (B18) per cent (overall chi 2 = 7.3, 2 d.f., P = 0.026). The Biopty gun with a 14-G needle results in a higher sampling success rate, greater diagnostic sensitivity and a better specimen quality than the Tru-Cut, and is much easier to use. PMID- 1422716 TI - Safety of fibreoptic endoscopy: analysis of cardiorespiratory events. AB - Cardiorespiratory function during upper gastrointestinal endoscopy and colonoscopy was studied prospectively in 164 patients. Cardiorespiratory events, which were defined as oxygen saturation < 90 per cent, electrocardiographic changes, heart rate < 50 or > 100 beats/min and systolic blood pressure < 100 mmHg, occurred in 111 patients. In 24 of these, changes were attributed solely to intravenous sedation. In the remaining 140 patients, events were noted in 34 (52 per cent) of 66 upper gastrointestinal endoscopies and during 53 (72 per cent) of 74 colonoscopies. One patient suffered a myocardial infarction during colonoscopy. Although cardiorespiratory events were common (111 of 164; 68 per cent), the actual morbidity rate was low (one of 164; 0.6 per cent). Cardiorespiratory events were significantly more common in patients with a history of cardiac disease for both upper gastrointestinal endoscopy and colonoscopy (overall chi 2 = 7.41, 1 d.f., P < 0.05) and more common for oesophageal dilatation than for diagnostic endoscopy (chi 2 = 5.56, 1 d.f., P < 0.05). It is recommended that patients with a history of cardiac problems undergoing upper gastrointestinal endoscopy or colonoscopy and all those requiring therapeutic endoscopy should be monitored carefully to allow early detection of cardiorespiratory events, and that oxygen should be administered routinely. PMID- 1422717 TI - Barrett's oesophagus: effect of antireflux surgery on symptom control and development of complications. AB - Forty-five patients with histologically proven Barrett's columnar-lined oesophagus (CLO) were treated in one unit over a 9-year period. Patients were studied prospectively as part of a surveillance programme; all initially received standard conservative treatment including high-dose H2-receptor antagonists. A satisfactory initial response was seen in 21 patients, but in 24 the symptoms were unchanged or progressed; 19 patients in the latter group were considered suitable for antireflux surgery and underwent fundoplication. Symptoms of heartburn or dysphagia persisted or recurred in 88 per cent of patients receiving medical treatment alone and complications developed in 38 per cent, including nine strictures and one adenocarcinoma. In patients undergoing antireflux surgery, symptoms persisted or recurred in 21 per cent and complications developed in 16 per cent (P < 0.01). Complete regression of Barrett's CLO occurred in two patients (11 per cent) after antireflux surgery. The results of this study suggest the superiority of antireflux surgery over pharmacological acid suppression in the control of symptoms and prevention of complications in patients with Barrett's CLO. PMID- 1422718 TI - Symptom index as a marker of gastro-oesophageal reflux disease. AB - Forty per cent of patients with heartburn may have no evidence of oesophagitis or of abnormal oesophageal acid exposure. The symptom index correlates symptoms that occur during pH monitoring with episodes of acid reflux, being the number of symptoms during reflux divided by the total number occurring during monitoring. This index was assessed in 61 patients with heartburn. In 39 patients with endoscopic evidence of oesophagitis or abnormal acid exposure times on pH monitoring, the symptom index had a sensitivity of 90 per cent. Of the 22 patients with no objective abnormality, the index was > or = 50 per cent in five (23 per cent) whose symptoms were presumably due to acid reflux despite results of other investigations being normal, suggesting an acid-sensitive oesophagus. The symptom index is a useful additional measure in the investigation of patients with suspected gastro-oesophageal reflux disease. PMID- 1422719 TI - Ambulatory measurement of oesophageal function: clinical use of a new pH and motility recording system. AB - Conventional oesophageal manometric studies are open to criticism in that they take place on fasted immobile subjects in the artificial setting of a motility laboratory. A new 24-h pH and motility recording system combined with computerized data analysis was used to study patients with gastro-oesophageal reflux disease and oesophageal motor abnormalities under ambulant conditions. Acid reflux episodes were found to be precipitated by a variety of events with recognizable pressure patterns. Acid clearance abnormalities were demonstrated in patients with erosive oesophagitis but were confined to those with abnormal oesophageal motor function. Improved diagnostic accuracy was demonstrated in the recognition of oesophageal motor disorders. PMID- 1422720 TI - Physiological and metabolic responses to open and laparoscopic cholecystectomy. AB - This study examined respiratory function and metabolic and subjective responses in patients undergoing laparoscopic (n = 10) and open (n = 11) cholecystectomy for chronic cholecystitis and biliary colic. Patient groups were matched for age, sex, weight and height. The duration of operation was similar in both groups. Respiratory function tests (vital capacity, forced expiratory volume in 1 s, peak flow and arterial blood gases), urinary cortisol, vanillylmandelic acid, metanephrines and nitrogen loss, serum complement component C3 and C-reactive protein (CRP), full blood count, erythrocyte sedimentation rate (ESR) and subjective responses as assessed on a pain analogue scale and by analgesic usage were determined for up to 48 h after surgery. Deterioration in perioperative respiratory function was significantly less for laparoscopic surgery. Arterial blood gas determinations indicated a greater perioperative decrease in arterial pH, with carbon dioxide retention in patients undergoing open cholecystectomy (P < 0.02), reflecting poorer respiratory performance. Hormonal profile changes demonstrated an increase in urinary vanillylmandelic acid in the laparoscopic cholecystectomy group (P < 0.04); no differences were detected in urinary cortisol, metanephrine or nitrogen excretion. Acute-phase responses were greatest in patients undergoing open cholecystectomy as determined by ESR and CRP level (P < 0.02 and P < 0.003, respectively). Pain and analgesic usage were significantly decreased in the laparoscopic cholecystectomy group (P < 0.0009) and P < 0.0001), which led to a decreased hospital stay after operation in these patients (P < 0.0001). These data indicate improved respiratory and subjective responses and diminished acute-phase responses associated with laparoscopic surgery. Catabolic hormone release may, however, be increased. PMID- 1422721 TI - Psychomotor testing and the ability to perform an anastomosis in junior surgical trainees. AB - Ten junior surgical trainees underwent objective testing of manual dexterity and visuospatial ability and were required to carry out five consecutive anastomoses on fresh porcine jejunum. Anastomoses were scored by a single observer and a cumulative error score (CES) derived for each procedure. In the first anastomosis there was little correlation between the psychomotor test results and the anastomosis scores. In subsequent trials there were significant negative correlations between aspects of manual dexterity and the CES. Over the five anastomoses there were significant negative correlations between improvement and manual dexterity, but there was a positive correlation between improvement and visuospatial ability (rs = 0.76, P < 0.005). Visuospatial skills are more important than pure motor ability in predicting the capacity to perform an anastomosis and tests of manual dexterity may be misleading in this context. PMID- 1422722 TI - Prospective randomized trial comparing the Shouldice technique and plication darn for inguinal hernia. AB - The lowest recurrence rates after inguinal hernia repair have been achieved by specialized hernia clinics. The Shouldice repair achieves success through application of a meticulous standardized operation carried out by specialist hernia surgeons. In a trial designed to rule out surgeon-dependent variables, 322 inguinal hernias were randomized prospectively to Shouldice repair or plication darn. Fifteen general surgeons operated on 322 patients. Fourteen surgeons in training not familiar with Shouldice repair received constant supervision for six repairs before independent operation. The mean (s.d.) patient age was 58.3(1.5) (range 20-84) years for Shouldice repair and 57.0(1.2) (range 18-85 years) for plication darn. The sex ratio (M:F) was 17:1 and right side to left side ratio 1.8:1. Six-week complication rates for wound infection (Shouldice repair, 5 per cent; plication darn, 4 per cent) and haematoma (Shouldice repair, 7 per cent; plication darn, 5 per cent) were similar in both groups. There were a similar number of sliding hernias in the Shouldice repair (14) and plication darn (20) groups. After a mean follow-up of 30 (range 24-48) months there were seven recurrences in the Shouldice group and four in the plication darn group (P > 0.05). The recurrences suggest that additional supervision of junior surgeons is required during the Shouldice repair learning period. PMID- 1422723 TI - Inguinal herniotomy in young infants. AB - Ninety-two consecutive infants aged up to 12 months underwent primary inguinal herniotomy over a 5-year period. All were treated in a district hospital paediatric surgical unit according to recommendations of the British Association of Paediatric Surgeons. After a mean follow-up of 45.8 months, one patient had a failed repair and four (4 per cent) a hernia recurrence. One infant developed a wound infection. Infantile hernia can be managed safely and efficiently in a district hospital. PMID- 1422724 TI - Comparative audit: an experimental study of 147,882 general surgical admissions during 1990. AB - In 1991, 1025 general surgical Fellows of The Royal College of Surgeons of England were circulated with a pro forma and asked to submit local audit results for admissions during 1990 to a confidential comparative audit service. The individual topics of cholecystectomy and colorectal resection were studied. Data returned by 160 surgeons concerned 147,882 admissions including 122,620 operations. Overall mortality rates ranged from 0 to 5 per cent and morbidity rates from 0 to 22 per cent. Laparoscopic cholecystectomy was associated with one quarter of the mortality rate and two-thirds the morbidity rate of open cholecystectomy. Of the 33 surgeons who responded to a survey after the presentation of results, all wished to continue the exercise in future years; 39 per cent had been stimulated to perform further analyses and 15 per cent had changed practice habits as a result. Comparative audit involving large numbers of patients and surgeons is feasible and seems beneficial to participants. PMID- 1422725 TI - Small bowel transit time in patients with intra-abdominal adhesions. PMID- 1422726 TI - Presentation of abdominal tuberculosis to general surgeons. AB - Abdominal tuberculosis (TB) continues to give rise to diagnostic and therapeutic challenges. A total of 24 patients with abdominal TB who presented to general surgeons over a 9-year period have been reviewed. Most (92 per cent) of these patients were Asian; only one had a past history of pulmonary TB. The most common presenting complaint was abdominal pain in 21 patients (88 per cent) with the associated symptoms of weight loss in 18 (75 per cent), anorexia in 15 (62 per cent) and night sweats in 13 (54 per cent). A tissue diagnosis was obtained in 18 patients (75 per cent) and 17 patients (71 per cent) underwent laparotomy. These results show that the diagnosis of abdominal TB is still difficult to establish, and that many patients undergo laparotomy despite the existence of less invasive diagnostic procedures. PMID- 1422727 TI - An improved means of faecal diversion: the trephine stoma. AB - Twenty-four patients in whom trephine stoma formation was performed over a 4-year period are described. This procedure permits the formation of an end ileostomy or colostomy without laparotomy. It is simple, rapid, safe and allows speedy recovery. It is widely applicable and previous abdominal surgery is no contraindication. The procedure was impossible in two patients who required laparotomy and in a third in whom a loop colostomy was created. Operation time was shorter and postoperative opiate requirements less than when laparotomy was undertaken for stoma formation. Follow-up (median 1 year) of 17 patients confirmed a low incidence of complications (two prolapses, one parastomal hernia) after trephine stoma formation. This procedure is recommended as the preferred method of ileostomy or colostomy formation when laparotomy is not otherwise indicated. PMID- 1422728 TI - Role of the rectum in the physiological and clinical results of coloanal and colorectal anastomosis after anterior resection for rectal carcinoma. AB - This study investigated the relationships between length of residual anorectum, anorectal physiological function and clinical outcome after anterior resection for rectal carcinoma. Thirty-four patients were studied a median of 13 (range 4 100) months after anterior resection. They were compared with a control group of ten patients who had undergone sigmoid colectomy for carcinoma without rectal excision. Resting anal pressure was found to be lower after coloanal than after colorectal anastomosis, and the capacity of the (neo)rectum was less after coloanal than after colorectal anastomosis. The (neo)rectoanal inhibitory reflex was found to be present in each patient, but maximum anal pressure during this 'sampling' reflex was significantly lower (P < 0.01) after coloanal than after colorectal anastomosis, and the volume required for maximal inhibition of the sphincter was also less (P < 0.01). At 1 year after operation, median bowel frequency was greater after coloanal (4 per day) than after colorectal (2 per day) anastomosis and the degree of urgency of defaecation was also greater (P < 0.01). Quality of life in terms of anorectal function after anterior resection is thus significantly influenced by the length of rectum that is left. This, in turn, influences the functional capacity of the neorectum and the degree of inhibition of the anal sphincter during the neorectoanal inhibitory reflex. PMID- 1422729 TI - Prevention of cardiovascular effects of endotoxaemia by monoclonal antibodies specific for core endotoxin. AB - Passive immunization with antibody to the core region of endotoxin (core lipopolysaccharide (LPS)) has been reported to reduce mortality in severe sepsis. A rat model of endotoxaemia that reproduces the hyperdynamic cardiovascular state seen in early sepsis was developed to test monoclonal antibodies specific for core LPS. A thermodilution technique of measuring cardiac output was adapted for use in rats. Twenty-five animals were anaesthetized and mechanically ventilated with monitoring of central venous pressure and mean arterial pressure. Fluid replacement was adjusted to maintain the central venous pressure. Controls (n = 10) and antibody-treated animals (n = 5) showed no significant change in cardiac output. Animals given 0.1 mg kg-1 R2 endotoxin over 1 h (n = 5) showed a significant rise in cardiac output of 65 per cent (P < 0.01). This was abolished in rats given both antibody and endotoxin (n = 5). This study provides evidence that a monoclonal antibody against core LPS abolishes the hyperdynamic state induced by endotoxin infusion. PMID- 1422730 TI - Prognostic significance of regional lymph node reaction after curative resection of advanced gastric cancer. AB - The prognosis of patients with advanced gastric cancer who undergo curative resection is still unsatisfactory. The relationship between prognosis and various factors such as stage, lymph node metastasis, serosal invasion and regional lymph node reaction (follicular hyperplasia and sinus histiocytosis) was evaluated. Of the factors studied, the only one that correlated well with survival was sinus histiocytosis. Lymph node metastasis was related weakly to prognosis. No correlation between prognosis and stage, serosal invasion or follicular hyperplasia was observed. Sinus histiocytosis may represent the morphological tumour-host immune reaction. Lymph node metastases or histological types were not related to regional lymph node reaction. These results suggest that sinus histiocytosis could be a useful prognostic factor for gastric cancer. Intensive postoperative follow-up for recurrence may be necessary even for patients with low-grade sinus histiocytosis in whom curative surgery is attempted. PMID- 1422731 TI - Perineal trauma from cassette tape boxes. PMID- 1422732 TI - Encephalopathy in patients with extrahepatic obstruction after lienorenal shunts. AB - Thirty patients with portal hypertension resulting from extrahepatic portal vein obstruction were studied. Evidence of postshunt encephalopathy was sought using neurological and psychometric tests and visual evoked potentials. Eleven patients were studied before and after lienorenal shunt operations and 19 at varying intervals, from 6 to 123 (median 26) months, after the same procedure. All the shunts were patent and none of the patients developed clinical or subclinical encephalopathy. In patients with extrahepatic portal vein obstruction, a lienorenal shunt does not appear to be associated with postshunt encephalopathy. PMID- 1422733 TI - Acute right iliac fossa pain in pregnancy: the role of fine-catheter peritoneal cytology. PMID- 1422734 TI - Physiological variation in rectal compliance. AB - The volume (V) of air inflated in a latex balloon placed in the rectum and the corresponding pressures (P) were measured in 48 subjects (24 men and 24 women) at three points: (1) earliest defaecation urge; (2) constant defaecation urge; and (3) maximum tolerable volume (MTV). The rectal pressures in all three cases were higher in men than in women. Woman aged over 60 years had higher rectal compliance (delta V/delta P) than men in the same age group, while no difference was found between men and women below the age of 60 years. Day-to-day variation of the measurements was tested in ten subjects. Reproducibility was good only for MTV (95 per cent confidence interval 57-183 per cent). Reproducibility of rectal compliance decreased with increasing values for this parameter. No such trend was found for the other parameters. In conclusion, MTV is a reproducible parameter and suitable for clinical use in evaluation of patients with faecal incontinence or constipation. PMID- 1422735 TI - Anterior resection without a defunctioning colostomy: questions of safety. PMID- 1422736 TI - Anterior resection without a defunctioning colostomy: questions of safety. PMID- 1422737 TI - Assessment of quality of life in surgery. PMID- 1422738 TI - Attitudes of cardiothoracic surgeons in the UK to human immunodeficiency virus. PMID- 1422739 TI - Laparoscopic operations in paediatric surgery. PMID- 1422740 TI - Tests of anorectal function. PMID- 1422741 TI - Endotoxin, septic shock and acute lung injury: neutrophils, macrophages and inflammatory mediators. AB - The treatment of septic shock remains a major problem in surgical practice. Current research on the pathogenesis of the sepsis syndrome focuses on the effects of the lipopolysaccharide constituents of bacterial endotoxin. Evidence suggests that endotoxin induces a whole-body inflammatory response that in turn mediates organ damage, eventually leading to multiorgan failure. The first organ in which failure is usually apparent is the lung, with the appearance of non cardiogenic pulmonary oedema as part of the adult respiratory distress syndrome. Inflammatory cells involved in lung injury include neutrophils and macrophages, which release mediators such as elastase, oxygen radicals and cytokines. This review summarizes current experimental work on how endotoxin leads to lung injury, based on its effects in animals and patients. Present knowledge suggests that future treatment of septic shock might involve inhibiting the body's inflammatory response to endotoxin. Possible ways of doing this are discussed. PMID- 1422742 TI - Unilateral parathyroid exploration. PMID- 1422743 TI - Surgical treatment of hidradenitis suppurativa. AB - The management of hidradenitis suppurativa is frequently unsatisfactory. No method satisfies all requirements for the ideal treatment--quick healing, no hospital admission, minimal patient inconvenience and low recurrence--but greater awareness of the strengths and weaknesses of existing methods should lead to improved management. Good reports of the relative cure rates of the different surgical options are scarce and controlled trials non-existent, but existing evidence is reviewed critically and summarized. The operation of choice in most instances is wide local excision and healing by secondary intention. PMID- 1422744 TI - Paediatric intussusception. AB - Intussusception is one of the commonest causes of intestinal obstruction in infants and accounts for about 700 hospital admissions each year in England and Wales. Improved results of treatment have followed recent technological developments, which include ultrasonographic imaging and pneumatic reduction techniques. Most intussusceptions can be reduced successfully without the need for operation but close cooperation between surgeon and radiologist is essential. Mortality and morbidity rates from the condition have progressively declined in recent decades but avoidable deaths still occur. PMID- 1422746 TI - Anatomy and function of the anal longitudinal muscle. AB - The longitudinal muscle in the intersphincteric space has received little attention despite an explosion of interest in anorectal physiology in the past decade. Its anatomy is contested and its function unknown. Speculation, however, gives it a role as a skeleton supporting and binding the rest of the internal and external sphincter complex together, as an aid during defaecation by everting the anus, as a support to the haemorrhoidal cushions, and as a determining factor in the ramification of sepsis. PMID- 1422745 TI - Perforated duodenal diverticulum. AB - Duodenal diverticula are present in up to 20 per cent of the population but few patients require surgery for acute complications. Perforation is the rarest of these complications; only 101 affected patients have been reported in the world literature. These reports of perforated duodenal diverticulum are reviewed and strategies for the diagnosis and management of this unusual condition are discussed. PMID- 1422747 TI - Assessment of stripping the long saphenous vein in the treatment of primary varicose veins. AB - Stripping of the long saphenous vein (LSV) may prevent recurrence of varices, although this has not been demonstrated using objective criteria. The aim of this study was to determine whether the addition of LSV stripping, from groin to upper calf, to saphenofemoral junction (SFJ) ligation prevents residual reflux, and whether LSV stripping to the upper calf results in greater neurological complications. Sixty-nine patients with primary varicose veins, LSV reflux and SFJ incompetence, confirmed by duplex ultrasonography and photoplethysmography, were studied. A total of 105 limbs were treated by SFJ ligation and avulsion of varices; patients were randomized to undergo stripping of the LSV to the upper calf (n = 49) or no additional treatment (n = 56). Three months after surgery all patients were examined clinically, by duplex ultrasonography and by photoplethysmographic tests of venous function, to establish the extent of persisting varices. Fewer persisting incompetent LSVs in the calf were found when the LSV was stripped (n = 9) than after SFJ ligation alone (n = 25) (P < 0.01). Photoplethysmographic refilling times were improved to a similar extent in both groups after surgery but were lower in those who had residual LSV reflux (P < 0.05). Six limbs developed paraesthesia in the distribution of the saphenous nerve: two in the group that were stripped and four in those that were not. These data suggest that LSV reflux is more completely abolished by combining LSV stripping with SFJ ligation; stripping the LSV to the upper calf does not result in a higher incidence of injury to the saphenous nerve. PMID- 1422748 TI - Duplex ultrasonography and pulse-generated run-off in selecting claudicants for femoropopliteal angioplasty. AB - Non-invasive assessment of lower limb vasculature may avoid unnecessary angiography in claudicants. Colour duplex ultrasonography of the femoral and popliteal arteries was performed to assess patency and the presence of any stenoses, and pulse-generated run-off (PGR) was used to assess the distal vasculature. In 65 legs colour duplex scanning was successful, compared with angiography, in identifying the site and type of disease in the femoropopliteal segment and 23 lesions were correctly identified as suitable for angioplasty. More patent distal vessels were demonstrated by PGR than by angiography; no vessels patent on angiography were missed by PGR. The estimated cost of diagnostic angiography was 330 pounds per test compared with 52 pounds for non invasive assessment. By using duplex examination as a screening test, a potential saving of 8062 pounds could have been made in this series. Duplex ultrasonography offers a non-invasive and cost-effective alternative to diagnostic angiography for clinically suspected infrainguinal arterial disease presenting as claudication. PGR was not of clinical value in assessing suitability for angioplasty. PMID- 1422749 TI - Selection for screening for familial aortic aneurysms. AB - The reported familial clustering of abdominal aortic aneurysm (AAA) indicates the possible rewards of family-based screening programmes with respect both to the number of asymptomatic aneurysms detected and to identifying associated genes. Ultrasonographic screening of 28 families (25 brothers and 28 sisters) was carried out together with collecting a history and a blood sample for analysis of the cholesterol level and genetic markers. Among the screened siblings six (11 per cent), all > 60 years old, had an AAA > or = 3.0 cm in diameter. A further 11 siblings (21 per cent), six of whom were < 60 years old, had a wide (2.5-2.9 cm) aorta. The presence of an aneurysmal or wide aorta was significantly associated with smoking (P = 0.027), male sex (P = 0.008) and a proband age of < 60 years (P = 0.031). Polymorphic genetic markers for type III collagen and haptoglobin were not informative in these families. These results indicate that the efficiency of screening siblings of patients with AAA could be improved by limiting it to brothers with a smoking history and/or siblings of younger patients. The familial component appears to be greatest in these younger patients. PMID- 1422750 TI - Storage of human pancreatic digest in University of Wisconsin solution significantly improves subsequent islet purification. AB - Density-gradient purification of human pancreatic islets from the collagenase digested pancreas relies on the exocrine tissue being denser than the islets. Cold storage of the pancreas before and after digestion causes cell swelling, which can decrease the density of pancreatic exocrine tissue and adversely affect subsequent purification. Using 14 human pancreata (seven perfused in situ with hyperosmolar citrate (HOC) and seven with University of Wisconsin solution (UW)), it is shown that storage of the pancreatic digest in UW significantly increases the density of pancreatic exocrine tissue compared with storage in minimal essential medium (MEM) (P = 0.009). This results in an improvement in islet purity (P = 0.036) for HOC- but not UW-perfused pancreata. Storage in UW for 1 h not only prevented the deterioration that occurred in MEM, but resulted in an improvement in islet purity for five of the seven HOC-perfused pancreata. Most pancreata in the UK are perfused with HOC, but storage of the digest in UW results in significantly better islet purity and, when islets cannot be purified immediately, a period of storage will often improve separation and allow islets to be purified. PMID- 1422751 TI - Randomized trial of loop ileostomy in restorative proctocolectomy. AB - A randomized controlled trial was performed to assess the role of loop ileostomy in totally stapled restorative proctocolectomy. Entry criteria included all patients who were not on corticosteroids in whom on-table testing revealed a watertight pouch with intact ileoanal anastomosis. Of 59 patients undergoing restorative proctocolectomy over 36 months, 45 were eligible and were randomized to loop ileostomy (n = 23) or no ileostomy (n = 22). The age and diagnosis of the groups were similar. There were no deaths; two ileoanal anastomotic leaks occurred, one in each group. Ileoanal stenosis occurred in five patients with and one without an ileostomy. The incidences of wound and pelvic sepsis, bowel obstruction and pouchitis were similar. Twelve patients (52 per cent) developed ileostomy-related complications. The median total hospital stay was 23 (range 13 75) days with ileostomy and 13 (range 7-119) days without (P < 0.001). This study indicates that there is a low risk of pelvic sepsis which is not increased by avoiding a protective ileostomy. Loop ileostomy was associated with a high incidence of complications. PMID- 1422752 TI - Screening patients with claudication from femoropopliteal disease before angioplasty using Doppler colour flow imaging. AB - Time, expense, risk and discomfort are incurred by arteriography in patients with intermittent claudication who might be candidates for percutaneous transluminal angioplasty (PTA). A valid screening technique could reduce the need for arteriography in patients found to have lesions not amenable to PTA. Agreement between Doppler colour flow imaging (DCFI) and angiography for detecting haemodynamically significant lesions is high, but DCFI may not identify lesions suitable for angioplasty. A total of 36 limbs in 30 patients were studied using DCFI before angiography. Agreement between the two methods was excellent (kappa = 0.91), and the predictive accuracy of DCFI for lesions amenable to PTA was good (kappa = 0.78, sensitivity 94 per cent, specificity 85 per cent, positive predictive value 83 per cent, negative predictive value 94 per cent, overall accuracy 89 per cent). DCFI is a useful screening process that may prevent unnecessary angiography, with consequent financial savings and clinical benefit. PMID- 1422753 TI - Radiation-induced acute femoral artery thrombosis treated by thrombolysis. PMID- 1422754 TI - Thromboembolic prophylaxis in total hip replacement: a comparison between the low molecular weight heparinoid Lomoparan and heparin-dihydroergotamine. AB - In a prospective, randomized, assessor-blind multicentre study two antithrombotic subcutaneous regimens were compared in patients undergoing total hip replacement. Group 1 (154 patients) received 750 anti-Xa units of a new low molecular weight heparinoid (Lomoparan) subcutaneously twice a day and group 2 (155 patients) received 5000 units heparin and 0.5 mg dihydroergotamine (heparin-DHE 5000) twice a day. The incidence of deep vein thrombosis, assessed by routine bilateral venography on day 10 (+/- 1), was 17 and 32 per cent in groups 1 and 2 respectively (risk reduction 47 per cent; P = 0.007). One patient in each group developed a symptomatic pulmonary embolism confirmed by lung scanning. Major bleeding complications occurred in one patient in each group and no significant difference was observed between the two groups with respect to minor bleeding complications. Subcutaneous Lomoparan appears to be as safe as heparin-DHE 5000 at the above doses with regard to bleeding complications, and is more efficacious with respect to venous thrombosis. PMID- 1422755 TI - Reduction of thrombus formation in vivo using a thrombolytic agent targeted at damaged endothelial cells. AB - Endothelial damage in saphenous vein harvested before coronary artery and peripheral vascular surgery has been well documented. Autogenous saphenous vein grafts are subject to early thrombotic occlusion, a process that is related to injury of this endothelial monolayer. A monoclonal antibody that binds to areas of endothelial damage (P14G11) and a non-specific immunoglobulin G (IgG) have been linked to urokinase. These conjugates were investigated in vivo using a rat vena cava model. The P14G11-urokinase conjugate significantly reduced thrombus formation compared with controls and non-conjugated urokinase (P < 0.02). No reduction in thrombus formation was seen with the IgG-urokinase conjugate. This shows that thrombus formation after endothelial damage in an in vivo model can be reduced with a targeted thrombolytic agent. Conjugates such as this may have a role in preventing early thrombotic occlusion in vein grafts. PMID- 1422756 TI - Recombinant basic fibroblast growth factor in red blood cell ghosts accelerates incisional wound healing. AB - The pharmacological manipulation of wound healing with locally applied growth factors is now a practical possibility. The effect of topical applications of recombinant basic fibroblast growth factor (bFGF) on the strength and cellularity of healing incisional rat skin wounds was investigated. Applications of bFGF in a simple vector (either a collagen suspension or saline) were not associated with any positive effects on wound breaking load at 7 days after injury in comparison with vector-treated control wounds; at the highest dose of 50 micrograms per wound, breaking loads were significantly decreased from a mean(s.e.m.) of 287(22) g/cm2 in controls to 201(23) g/cm2 (P < 0.005). Increasing doses of applied peptide were paralleled by increasing wound cellularity. Delay of bFGF release at the site of application was achieved by encapsulation into red blood cell ghosts. Wounds treated with bFGF in such ghosts were 50 per cent stronger than paired control wounds (388(27) versus 256(28) g/cm2, P < 0.002) 7 days after injury. Treated wounds were significantly more cellular at 4 days than paired control wounds. Topical applications of bFGF applied at the time of injury exert a positive effect on incisional wound strength only when a vector that delays release is used. PMID- 1422757 TI - Results of the first year of breast cancer screening in a district hospital. AB - The Humberside Breast Screening Service completed 1 year of screening by October 1990; 16,534 women were invited of whom 12,832 (77.6 per cent) attended. A group of 644 women (5.0 per cent) were called for further assessment and of these 134 underwent 135 primary surgical procedures. After assessment 25 were shown before operation to have cancer. One hundred and nine women had suspicious lesions and proceeded to surgical biopsy; 50 lesions proved malignant (benign: malignant biopsy ratio 1.2:1). The 75 malignant lesions represented a prevalence of 5.8 per 1000 of the screened population. Invasive cancer > 1 cm in diameter formed almost half of the malignant lesions. This service has cost 32 pounds per woman screened or 5533 pounds per cancer detected. The results are comparable to those of previous studies and suggest that a mammographic screening service can be successfully provided in a district hospital setting. PMID- 1422758 TI - Assessment of non-palpable mammographic abnormalities: comparison between screening and symptomatic clinics. AB - A retrospective study found that a breast screening clinic generated fewer localization biopsies for non-palpable mammographic abnormalities than a symptomatic clinic (3.36 versus 9.89 per 1000 mammograms, respectively) and that a greater proportion of such biopsies were malignant. This study determined the reason for this difference. There were 108 of 304 (35.5 per cent) and 17 of 130 (13.1 per cent) carcinomas in women attending the screening and breast clinics respectively (relative risk 2.72 (95 per cent confidence interval 1.70-4.34)). This difference was regardless of age. The characteristics of the mammographic abnormality, the Wolfe pattern, a family history of breast carcinoma, parity and age at first pregnancy were similar in both groups. Women attending the screening clinic were referred for localization biopsy after assessment by clinicians and radiologists at a joint clinic; there was no joint assessment for patients attending the breast clinic. The same staff attended both clinics, although the proportion of time spent at each varied. This study suggests that all women with a non-palpable mammographic abnormality should be reviewed at a joint assessment clinic before localization biopsy is recommended. PMID- 1422759 TI - Disposable guarded trocar and cannula in laparoscopic surgery: a caveat. PMID- 1422760 TI - Smoking predisposes to parotid adenolymphoma. AB - Of 574 patients with previously untreated, unremarkable parotid lumps, 194 proved to have pleomorphic adenomas and 73 adenolymphomas. ABO blood group details were available in 59 and 85 per cent of patients respectively. Smoking details were available in 84 per cent of a randomly chosen 46 per cent subgroup of patients with pleomorphic adenomas and in 86 per cent of all those with adenolymphomas. The incidences of smoking and of the ABO blood groups in these two diagnoses were compared with standard sources. There was no evidence that either histological diagnosis of parotid tumours was linked to an abnormal pattern of ABO blood groups. However, there was a much greater incidence of smoking among the adenolymphoma than in the pleomorphic adenoma group: only one of 63 patients with adenolymphoma as opposed to 31 of 75 with pleomorphic adenoma had never smoked, while the mean number of cigarettes smoked by each patient with an adenolymphoma was estimated to be 300,000 as opposed to 80,000 for those with pleomorphic adenoma. PMID- 1422761 TI - Surgery for primary hyperparathyroidism performed under local anaesthesia. AB - Patients with primary hyperparathyroidism are often elderly with cardiovascular disease and in some an operation might be hazardous owing to anaesthetic complications. A technique for operation for primary hyperparathyroidism under local anaesthesia is described. The method uses a unilateral approach. Seventeen consecutive patients operated on under local anaesthesia were compared with a group of 15 patients undergoing surgery under general anaesthesia. Normocalcaemia was achieved in 14 patients in each group. There was no difference in the extent of pain or the overall well-being between the two groups as determined by a visual analogue scale. Patients receiving local anaesthesia, however, experienced significantly less nausea after operation (P < 0.01). There was more fluctuation in blood pressure and heart rate in the general anaesthesia group compared with the other group. Surgery for primary hyperparathyroidism can be performed safely under local anaesthesia, and could be offered to patients if general anaesthesia were not suitable or involved an increased perioperative risk. It should not be recommended for routine use in patients who are fit for general anaesthesia. PMID- 1422762 TI - Surgical resection for stage I cancer of the oesophagus and cardia. AB - A study was carried out to establish the long-term survival of patients with stage I carcinoma of the oesophagus and cardia, and to assess the influence of various factors on the 5-year survival rate. The study, which was partly prospective and partly retrospective, involved 60 patients with early (stage I) carcinoma of the oesophagus or cardia from a total of 811 consecutive patients with such carcinomas who were referred to one regional centre over a 15-year period, 425 of whom underwent resection. Survival at 5 years was taken as the main measure of outcome. Forty-two patients (70 per cent) were alive at 5 years. None of the factors studied (sex, age, site or histological type of tumour) had a significant effect on outcome. PMID- 1422763 TI - Oesophageal reflex responses: abnormalities of the enteric nervous system in patients with oesophageal symptoms. AB - An intraluminal balloon was used to study the peristaltic reflex, which is mediated by the intrinsic nerves of the oesophagus. Serial balloon distension was performed in nine asymptomatic volunteers and 133 patients with oesophageal symptoms. Eight of the volunteers had a normal response with proximal stimulation and distal inhibition of motility. Only 42 patients (31.6 per cent) had a normal response. The commonest abnormal response (39.1 per cent) was some form of failure of the distal inhibitory reflex. Other patterns of abnormality were an unresponsive oesophagus (15.8 per cent) with no motility change during balloon inflation, or spasm (13.5 per cent) proximal to the balloon. These alterations of secondary peristaltic activity suggest that there are abnormalities of the intrinsic (enteric) nerves of the oesophagus. Different abnormalities were found in patients with similar symptoms. Awareness of this difference might allow a more rational approach to treatment. This hypothesis was tested in a small pilot study treating functional dysphagia with cisapride. Three of nine patients had marked symptomatic improvement within 4 weeks and all three had an unresponsive oesophagus. The remaining six patients, who had failure of distal inhibition or a normal response, did not improve. PMID- 1422764 TI - Thoracoabdominal oesophageal duplication. PMID- 1422765 TI - Adequacy of paracardial dissection in subtotal versus total gastrectomy. AB - Right and left paracardial dissection represents an obligatory step in gastrectomy for gastric cancer of the lower half of the stomach because a second level lymphadenectomy is part of the radical surgery for malignancy at this site. Whereas right and left paracardial dissection is easily accomplished during total gastrectomy, there is doubt as to whether subtotal gastrectomy achieves the same radical clearance of these groups of lymph nodes. This study therefore compared the number of lymph nodes dissected and the frequency of metastases in these compartments in 14 patients undergoing total gastrectomy and 22 submitted to subtotal gastrectomy. The mean number of lymph nodes dissected in the right paracardial compartment was 7.1 per patient undergoing total gastrectomy and 6.7 per patient in subtotal gastrectomy (P = 0.7). The mean numbers of left paracardial lymph nodes dissected in total and subtotal gastrectomy were 3.4 and 4.1 per patient respectively (P = 0.3). These data show that the same degree of radical clearance can be achieved in these nodal compartments, irrespective of the extent of gastric resection. PMID- 1422766 TI - Place of routine operative cholangiography at cholecystectomy. PMID- 1422767 TI - Isolated hyperthermic liver perfusion with cytostatic-containing perfusate activates the complement cascade. AB - Eight patients with advanced liver malignancy undergoing isolated hyperthermic liver perfusion with melphalan and cisplatin were studied with regard to complement activation and formation of anaphylatoxins (C3a and C5a) and terminal C5b-9 complement complexes (TCCs). Blood samples for complement variables (C1 INH, C3, C4, C5, C3a, C5a and TCCs) were taken before surgery, 1 min before the start of perfusion, 1, 2 and 3 h after the start of perfusion, and 24 h after operation. Samples were drawn from the perfusate 1 h after the start of perfusion. Activation of complement was observed during perfusion. Raised plasma concentrations of C3a and TCCs were recorded and high levels of C3a and TCCs were found in the perfusate. In vitro tests indicated that melphalan and cisplatin may activate complement. This activation occurred at 37 and 42 degrees C but was more pronounced at 42 degrees C. PMID- 1422768 TI - Fat-wrapping in Crohn's disease: pathological basis and relevance to surgical practice. AB - The connective tissue changes that accompany intestinal Crohn's disease have received little attention from pathologists. This is particularly so with fat hypertrophy, and yet surgeons have long recognized the phenomenon of fat-wrapping in the intestines and used it to delineate the extent of active disease. A consecutive, unselected series of 27 intestinal resections performed on 25 patients for histologically confirmed Crohn's disease was studied to correlate fat-wrapping with other clinicopathological features. Fat-wrapping was identified in 12 of 16 ileal resections and in seven of 11 large bowel resections. It correlated closely with transmural inflammation and there was a relationship between fat-wrapping and other connective tissue changes including fibrosis, muscularization and stricture formation. Morphometry demonstrated that there was true hypertrophy and that fat-wrapping does not relate solely to bowel wall shrinkage. There was correlation with ulceration but in 11 cases macroscopic ulceration extended beyond the fat-wrapping and in six to surgical resection margins. The pathological features of 225 small intestinal resections were reviewed and fat-wrapping was seen only in Crohn's disease. Fat-wrapping correlates best with transmural inflammation and represents part of the connective tissue changes that accompany intestinal Crohn's disease. Findings also suggest that fat-wrapping alone should not be used as an accurate marker of disease extent at the time of surgery. PMID- 1422769 TI - Zinc-deficient diet impairs adaptive changes in the remaining intestine after massive small bowel resection in the rat. AB - An investigation was conducted on the influence of the presence of zinc in an elemental diet on the mucosa of residual intestine after massive small bowel resection. A total of 34 male Sprague-Dawley rats were divided into five groups: control animals (n = 10) were killed after overnight fasting; a second group (n = 14) underwent massive small bowel resection preserving 10 cm of terminal ileum, and the third group (n = 10) underwent sham operation. Animals in the second and third groups were fed either a commercially available elemental diet or a zinc deficient diet for 2 weeks; they were then killed. In animals receiving the zinc deficient diet, a significant decrease (P < 0.05) was noted in plasma zinc and total protein, and in mucosal wet weight (duodenum), thickness (duodenum and ileum), and protein (duodenum) and DNA (duodenum) content. Mucosal sucrase and maltase specific activities in the duodenum and ileum fell but diamine oxidase levels did not. These results suggest that zinc plays an important role in intestinal adaptation in the rat, and indicate that this trace element is essential for intestinal mucosal preservation in this animal. PMID- 1422770 TI - Exteriorization of an ovary: an unusual complication of abdominal drainage. PMID- 1422771 TI - Laparoscopy in developing countries in the management of patients with an acute abdomen. AB - Surgeons in developing countries see a need to improve diagnosis and decision making in patients with an acute abdomen. Without the benefit of diagnostic aids such as computers and high-resolution ultrasonography, the rate of unnecessary laparotomy is often unacceptably high. The laparoscope is usually available in a developing country and its use easily acquired. Using laparoscopy in doubtful situations the unnecessary laparotomy rate was significantly reduced from 14.0 to 6 per cent (P < 0.05). Laparoscopy achieved a diagnostic accuracy of 86 per cent and prevented unnecessary laparotomy in 57 per cent of those in whom it was used. PMID- 1422772 TI - The missing appendix. PMID- 1422773 TI - Laparoscopic approach to Meckel's diverticulectomy. PMID- 1422774 TI - Quality of life after gastrectomy in patients with carcinoma of the stomach. PMID- 1422775 TI - Upper thoracic sympathectomy for primary palmar and axillary hyperhidrosis: long term follow up. PMID- 1422776 TI - Recombinant tissue-type plasminogen activator is superior to streptokinase for local intra-arterial thrombolysis. PMID- 1422777 TI - Laparoscopic vagotomy: a new tool in the management of duodenal ulcer disease. PMID- 1422779 TI - The changing face of foot-and-mouth disease (FMD) control. PMID- 1422778 TI - Predeposit autologous blood transfusion in patients with colorectal cancer: a feasibility study. PMID- 1422780 TI - Understanding the pathogenesis of equine osteoarthritis. PMID- 1422781 TI - Equine chondrocyte activation by a variety of stimuli. AB - There is increasing evidence that the chondrocyte is capable of considerable anabolic and catabolic activity. In the case of equine chondrocytes, this study demonstrates that a variety of factors involved in the pathogenesis of joint disease stimulate the production of prostaglandin E2. These include exposure to IL-1, bone fragments and LPS. In addition, an IL-1-like factor was shown to be produced by the chondrocyte itself, when stimulated by LPS, providing a possible mechanism for amplification of extra-cartilagenous signals and even autocrine control. Considered together with evidence of increased synthesis of proteoglycan molecules by chondrocytes in diseased cartilage, this offers the exciting possibility of development of therapeutic agents to assist cartilage repair. PMID- 1422782 TI - A study on the effects of the rapid intravenous infusion of hypertonic Na and K solutions into normal conscious sheep on some cardiac characteristics and blood analytes. AB - Five normal, conscious, aged Merino ewes were infused with 200 ml of an aqueous solution containing 5% NaCl and 0.25% KCl (HNaK) at a mean rate of 0.024 ml/kg/s and four similar sheep with 0.9% saline at a mean rate of 0.018 ml/kg/s. Five ECG tracings were obtained over a 6-h period--two (20 s each) before, one (continuous tracing) during the infusion, and two (20 s each) afterwards. The heart was auscultated during the infusion. Seven heparinized blood samples were obtained- three before the infusion (1.5 h, 1.0 h, and immediately before), and four afterwards (immediately, 2.5 h, 4.5 h, and 24 h after). Determinations were made of changes in mean PCV, red cell counts, mean corpuscular volumes, plasma Na, K, Ca and Mg, and of erythrocyte Na and K concentrations. Analysis of variance revealed increases in heart rate when the results from both groups were combined, but no significant effects on cardiac rhythm. Auscultation revealed marked fluctuations in cardiac intensity within individual sheep and marked differences between sheep, particularly in those infused with HNaK. In the HNaK group there were significant increases in erythrocyte and plasma Na, and erythrocyte K and decreases in plasma Ca during the infusion. Plasma K increased from the termination of the infusion to 2.5 h afterwards in the saline group but decreased unexpectedly during the same period in the group infused with HNaK [corrected]. PMID- 1422783 TI - Blood pathophysiological changes in sheep following a prolonged (18-hour) period of hypocalcaemia induced by Na2EDTA solution. AB - Six aged Merino ewes were used in an experiment in which five were infused with 4.7% Na2EDTA solution intravenously for 18 h at a rate designed to produce hypocalcaemia and maintain recumbency, and five with 0.9% sodium chloride solution at the same rate for the same period (four were infused at different times with both solutions). Blood samples were collected every 3 h and determinations made of plasma Ca, Na, K, Mg, and inorganic P (PiP), erythrocyte Na, K and Mg, and PCV. Three of the hypocalcaemic sheep took 36-64 h to regain their feet. Plasma Ca and K, and erythrocyte Na showed significant (all P less than 0.01) decreases in the group infused with Na2EDTA compared with the group infused with saline while PCVs were significantly (P less than 0.01) greater in the former group. The sheep model used could be suitable for the study of the effects of prolonged hypocalcaemia and recumbency in cows. PMID- 1422784 TI - Determination of the length and position of the lower oesophageal sphincter (LOS) by correlation of external measurements with combined radiographic and manometric estimations in the cat. AB - Fifty DSH cats were studied radiographically and a highly significant linear correlation was found between the length of the oesophagus measured to the diaphragmatic line on the radiographs and the externally measured distance from the lower jaw incisor teeth to the anterior border of the head of 10th rib. A subsequent manometric study utilizing this correlation in 40 cats suggests that the functional lower oesophageal sphincter (LOS) is situated almost at the level of the diaphragm in the cat. Significant differences were found between the length of the LOS in cats anaesthetized with ketamine compared to alphaxalone alphadolone or xylazine-ketamine-atropine. The mean lengths of the LOS was 1.42 +/- 0.3 cm. The findings of this study indicate that external measurements can be used to position catheters for accurate oesophageal manometry in the cat. PMID- 1422785 TI - The prevalence of Salmonella infections in camels (Camelus dromedarius) in the United Arab Emirates. AB - One hundred and eighty-seven salmonella strains were isolated from 4006 samples collected from camels in the United Arab Emirates between 1987 and 1991. One hundred and sixty-five (4.3%) strains were isolated from 3801 faecal and 22 from 205 organ samples of 62 autopsied camels. In total, 28 different serotypes were identified with S. saintpaul being the most frequent (69), followed by S. frintrop (31) and S. hindmarsh (15). Salmonella typhimurium was isolated from only two faecal specimens. All salmonellas isolated from faecal samples originated from carrier camels, and those isolated from organs were secondary findings. The camels from which salmonella organisms were found died from diseases other than salmonellosis. Most of the S. saintpaul isolates originated from one herd suffering from Clostridium perfringens type A enterotoxaemia which suggests that salmonella infections may predispose camels to clostridial enterotoxaemias. PMID- 1422786 TI - Serial thyroid hormone concentrations in healthy euthyroid dogs, dogs with hypothyroidism, and euthyroid dogs with atopic dermatitis. AB - Serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) concentrations were determined every 3 h for 12 h beginning at 8 a.m. in 20 healthy euthyroid dogs, 19 dogs with hypothyroidism, and 18 euthyroid dogs with atopic dermatitis. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, and requirement for thyroid hormone replacement therapy. Mean serum T4 and T3 concentrations did not vary significantly between blood samplings within each of the three groups of dogs. Between groups of dogs, mean serum T4 concentration was significantly (P less than 0.05) higher at each blood sampling time in healthy euthyroid dogs and euthyroid dogs with atopic dermatitis when compared to dogs with hypothyroidism. There was no significant difference in mean serum T4 concentration at any blood sampling time between healthy euthyroid dogs and euthyroid dogs with atopic dermatitis or in mean serum T3 concentrations at any blood sampling time between any of the three groups of dogs. Random fluctuation in serum T4 and T3 concentrations was found in dogs in all three groups. Random fluctuations were more common with serum T3 versus T4 concentrations. Consequently, sensitivity (0.88 versus 0.52), specificity (0.73 versus 0.45), predictive value for a positive test (0.75 versus 0.32), predictive value for a negative test (0.87 versus 0.65), and accuracy (0.80 versus 0.47) were better for serum T4 concentration than serum T3 concentration, respectively, when all blood samples were analysed. Measurement of serum T4 concentration was more accurate than serum T3 concentration in assessing the status of thyroid gland function. PMID- 1422787 TI - Oestradiol-17 beta in the milk of cows from 6 days before to 14 days after their insemination. AB - In artificially inseminated cows (AI on day 1) peak concentrations of oestradiol 17 beta in defatted milk occurred at median times of day 0 during the pre ovulatory period, days -5 to 2, and day 6 during the post-ovulatory period, days 2-15. Median peak concentrations during these periods were approximately 5 pg/ml and 3 pg/ml respectively. There were no significant differences in the timing or magnitude of oestradiol-17 beta concentrations between cows that became pregnant to the AI and those that entered normal length oestrus cycles immediately after AI. PMID- 1422788 TI - Quinolinic acid and kynurenine pathway metabolism in inflammatory and non inflammatory neurological disease. AB - Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy. PMID- 1422790 TI - Neurology of latent nystagmus. AB - We report eye movement findings in 30 patients with latent nystagmus and who were found to have a variety of associated oculomotor disorders. Latent nystagmus is defined clinically as nystagmus which appears on covering one eye and beats towards the uncovered eye. Recordings showed that the latent nystagmus in 28 patients had slow phases with linear or exponentially decreasing velocity. This nystagmus is termed 'LN'. In 13 of these patients certain manoeuvres (e.g. pursuit) provoked nystagmus with exponentially increasing slow phase velocities characteristic of the congenital form of nystagmus termed 'CN' and we propose that this is a forme fruste of CN. In two patients the nystagmus provoked by cover was latent CN. Twenty-nine patients had a history of strabismus and one had a marked phoria. Some patients had amblyopia whilst others had normal vision in each eye. Although binocular vision was usually absent, six patients had varying degrees of stereopsis. A temporonasal predominance of monocularly elicited optokinetic response previously associated with LN, was present only in a minority of patients. Some responses were bidirectionally absent or of low velocity, possibly the result of a cortical impairment of visual motion detection. The most deranged responses had slow phases which were in the opposite direction to the stimulus as described in CN. The presence of 'forme fruste' CN in many of these patients suggests that some of the derangements of optokinetic responses are due to CN. The findings indicate a greater overlap between the incidences of LN and CN than previously estimated. Thirty percent of patients had large saccadic 'square wave' intrusions. These were not present when there was marked amblyopia. They are attributed to a competitive incongruence of visual fields and eye positions. Dissociations found between the presence and severity of strabismus, stereopsis, amblyopia and optokinetic abnormalities point to these features being relatively independent although associated in typical clusterings. This is evidence against the theory that strabismus and LN are directly caused by nasotemporal optokinetic imbalance which persists because of failure to develop binocular vision. The variability of findings favours the view that LN and CN arise from a genetic or acquired embryological disorder with various degrees and directions of expression. PMID- 1422789 TI - Motor nerve inexcitability in Guillain-Barre syndrome. The spectrum of distal conduction block and axonal degeneration. AB - We studied 34 patients with the Guillain-Barre syndrome (GBS) to clarify the clinical significance of inexcitable motor nerves and of low amplitude compound muscle action potentials (CMAPs). The patients were subdivided into two groups. Group 1 included eight patients who had electrically inexcitable motor nerves within 2 wks of the first symptom. (Two patients without extensive conduction studies had only one inexcitable motor nerve.) The outcome in this group at 1 yr varied from complete recovery (five patients) to severe motor sequelae (three patients). Group 2 included 26 patients who had two electrophysiological assessments, and in whom the serial changes in CMAP amplitudes were analysed and correlated to outcome. Fourteen of these 26 sets of serial studies were performed within 1 mth. Twelve of 26 patients in Group 2 showed decrease in the amplitude of CMAPs between serial studies; only six of these had a good outcome at 1 yr. Nine of 26 patients showed increase in CMAP amplitude between serial studies, of these eight had a good clinical outcome. Low-amplitude CMAPs or inexcitable motor nerves in the initial stages of GBS are due to distal pathology of the motor axons, either distal conduction block or axonal degeneration. The nature of these changes cannot be predicted by the results of the initial electrophysiological evaluation, including the presence or absence of active denervation. However, improvement of CMAP amplitude on sequential studies suggests a good outcome at 1 yr. We believe that, in the absence of a biological marker for GBS, individualization of an 'axonal variant' of the syndrome is not warranted at the present time. PMID- 1422791 TI - Comparison of predictable smooth ocular and combined eye-head tracking behaviour in patients with lesions affecting the brainstem and cerebellum. AB - We compared the ability of eight normal subjects and 15 patients with brainstem or cerebellar disease to follow a moving visual stimulus smoothly with either the eyes alone or with combined eye-head tracking. The visual stimulus was either a laser spot (horizontal and vertical planes) or a large rotating disc (torsional plane), which moved at one sinusoidal frequency for each subject. The visually enhanced vestibulo-ocular reflex (VOR) was also measured in each plane. In the horizontal and vertical planes, we found that if tracking gain (gaze velocity/target velocity) for smooth pursuit was close to 1, the gain of combined eye-hand tracking was similar. If the tracking gain during smooth pursuit was less than about 0.7, combined eye-head tracking was usually superior. Most patients, irrespective of diagnosis, showed combined eye-head tracking that was superior to smooth pursuit; only two patients showed the converse. In the torsional plane, in which optokinetic responses were weak, combined eye-head tracking was much superior, and this was the case in both subjects and patients. We found that a linear model, in which an internal ocular tracking signal cancelled the VOR, could account for our findings in most normal subjects in the horizontal and vertical planes, but not in the torsional plane. The model failed to account for tracking behaviour in most patients in any plane, and suggested that the brain may use additional mechanisms to reduce the internal gain of the VOR during combined eye-head tracking. Our results confirm that certain patients who show impairment of smooth-pursuit eye movements preserve their ability to smoothly track a moving target with combined eye-head tracking. PMID- 1422792 TI - A quantitative study of eye and head movements during smooth pursuit in patients with cerebellar disease. AB - Eye and head movements were analysed during smooth pursuit in 16 patients with various forms of cerebellar disease. Smooth pursuit gain was reduced across all frequencies and velocities of target motion for the patient group as a whole, during both sinusoidal and pseudo-random target motion. The graded breakdown in the pursuit response, as pseudo-random target motion became less predictable, was of a similar magnitude in patients and controls, implying that the predictive pursuit mechanisms were intact in these patients. During head-free pursuit, when vestibulo-ocular reflex (VOR) suppression was necessary, performance was not significantly different from that observed during head-fixed pursuit in the patient group. This finding is similar to that noted in control subjects, and is consistent with the observation that the VOR gains associated with head movements in darkness were similar in the patient and control groups. The deficits in pursuit and VOR suppression in patients with cerebellar disease therefore represent a decrease in gain in the closed-loop visual feedback pathways with apparent sparing of the predictive pathways. PMID- 1422793 TI - Saccadic reaction times in patients with frontal and parietal lesions. AB - The effect of unilateral circumscribed lesions in different areas of the frontal and parietal cortex on the distributions of saccadic reaction times (SRTs) was investigated in 32 patients under four stimulus conditions: (i) gap-random: a target light appeared 200 ms after extinction of a central fixation light randomly at 8 degrees either left or right; (ii) overlap-random: like (i), but the fixation light remained on ('overlap'); (iii) gap-simultaneous: two peripheral lights appeared simultaneously left and right 200 ms after the extinction of the fixation light, one predesignated by instruction as saccadic target; (iv) overlap-simultaneous: like (iii), but the fixation light remained on. Depending on SRT and condition and based on the data of control subjects, we evaluated the percentages of anticipatory (SRT: 0-90 ms), express (91-157 ms) and regular (158-400 ms) saccades, of time (> 400 ms) and direction errors as well as the mean latencies and the standard deviations. These data were compared across control subjects, frontal lobe patients with a lesion in the region of the frontal eye field (FEF), and frontal patients with a lesion outside the FEF, as well as across control subjects, parietal lobe patients with a lesion in the dorsolateral region, and parietal patients with a lesion outside the dorsolateral region. (i) Frontal patients with a lesion in the FEF region showed an increased percentage of express saccades (gap-random condition), especially with saccades directed towards the side of the lesion (ipsilateral). If fixation was not interrupted prior to target appearance (overlap-random), express saccades were largely suppressed, similar to normals. All patients with a frontal lesion, whether in the region of the FEF or not, showed a decreased percentage of contralateral anticipatory saccades (gap-simultaneous), whereas the percentages of direction and time errors were in the normal range, even if more than one stimulus was presented (e.g. overlap-simultaneous condition). (ii) Patients with dorsolateral parietal lesions showed decomposed SRT patterns (high SRT variability, increased percentages of time and direction errors, decreased percentages of express and anticipatory saccades). The decomposition had a contralateral preponderance and increased if more than one stimulus was visible beside the saccadic target. Our results suggest that FEF lesions impair mainly the volitional control over visually triggered express or reflex-like saccades if fixation is disrupted, whereas dorsolateral parietal lesions impair mainly the selection of the visual targets. PMID- 1422794 TI - Saccadic dysmetria in a patient with a right frontoparietal lesion. The importance of corollary discharge for accurate spatial behaviour. AB - Double-step experiments have demonstrated that retinotopic coding is inadequate to explain the spatial performance of the saccadic system. In such experiments a subject is asked to make two successive saccades to fixate two sequentially flashed targets each of which disappears before the first saccade. Despite the dissonance thus created between the retinal location of the second target and the saccade necessary to acquire it, normal humans and monkeys perform the task perfectly well. Single unit recording in monkeys indicates that neurons in the superior colliculus, frontal eye fields and in parietal cortex generate a spatially accurate signal during the performance of double-step saccades, which is thought to be obtained by combining a retinotopic signal with a signal corollary to the previous saccadic eye movement. We studied saccadic eye movements in a patient with a right fronto-parietal lesion using single- and double-step tasks. Single saccades into the left (contralesional) hemifield had longer latency and were hypometric relative to those into the right (ipsilesional) hemifield. Varying the initial orbital position had no effect on the latency and accuracy of saccades to left and right retinal stimuli. When the patient was asked to do a double-step task with targets flashed first into the right field and then into the left field, she performed well. When she was asked to do the same task with a target flashed first into the left field and then into the right field she made the first saccade correctly but never acquired the second target, even though this required her to make a saccade in the normal direction to a stimulus that appeared in the normal field. Such a deficit therefore cannot be one of retinotopic or spatial coding, nor can it be one of generating a certain direction of saccade. We suggest that the deficit is a failure of corollary discharge, the inability to register the amplitude and direction of a saccade into the contralesional field, and use that information to update the representation of the location of the next saccade target. PMID- 1422795 TI - Acute optic neuritis. A cognitive and magnetic resonance imaging study. AB - Forty-two patients with acute optic neuritis (ON) (mean duration of symptoms 14.5 d) were compared with a matched, normal control group on a battery of tests of attention and information processing speed. Approximately half the sample (55%) had brain abnormalities shown by magnetic resonance imaging (MRI) and were more impaired across a variety of tests compared with those patients without brain lesions or normal controls. There was no difference in psychometric performance other than the pegboard task between the normal control group and those ON patients without brain involvement. Significant correlations were found between total lesion area in the brain and some tests of attention. Results from the Symbol Digit-Substitution Test were particularly sensitive in this regard and could correctly identify 70% of the sample with brain lesions. PMID- 1422796 TI - The mechanism of facial sweating and cutaneous vascular responses to painful stimulation of the eye. AB - The vascular response in the forehead and cheeks to irritating the eye with soapy water was measured in 15 normal subjects. Electrodermal activity, which reflects sweating, was also measured from both sides of the forehead. The mechanism of the response was studied in 15 patients with a unilateral lesion of the facial nerve blocking parasympathetic outflow. Pulse amplitude usually increased briefly on both sides of the forehead after the soap was placed in the eye; the response persisted for several minutes on the ipsilateral side after the soap had been washed from the eye. A facial nerve lesion blocked the vascular response on the lesioned side to stimulation of either eye. No consistent change in pulse amplitude was recorded from the cheeks, although a response was observed in a few subjects. Electrodermal responses to ocular irritation were generally larger on the ipsilateral than contralateral side of the forehead; in patients with facial palsy, electrodermal responses were greater on the normally innervated side than on the lesioned side. The findings suggest that irritating the eye induces a trigeminal-parasympathetic vasodilator reflex and local sweating. The restricted distribution of the response indicates that separate parasympathetic vasodilator reflexes might operate for each division of the trigeminal nerve. PMID- 1422797 TI - Pathological sweating and flushing accompanying the trigeminal lacrimal reflex in patients with cluster headache and in patients with a confirmed site of cervical sympathetic deficit. Evidence for parasympathetic cross-innervation. AB - Electrodermal responses (as a measure of sweating) and vascular responses to irritation of the eye were investigated in 11 cluster headache patients and, for comparison, in another 24 patients with a confirmed site of lesion in the cervical sympathetic pathway. Seven of the cluster headache patients had ocular and thermoregulatory signs of a postganglionic sympathetic lesion. In these patients, and in six of seven patients with a postganglionic sympathetic lesion from some other cause, the electrodermal response to ocular stimulation was far greater on the denervated side of the forehead than on the sympathetically intact side. This pathological response can be explained by lacrimotor fibres branching into vacant sympathetic sudomotor pathways. The response could account for excessive forehead sweating during attacks of cluster headache, in spite of the presence of Horner's syndrome, because parasympathetic outflow to the lacrimal glands increases during attacks. In patients with diminished sympathetic vasomotor outflow, the vascular response to ocular irritation was also greater on the denervated side of the forehead than on the sympathetically intact side, irrespective of the site of the lesion. The excessive vascular response in sympathetically denervated skin could be caused by adaptive supersensitivity to peptides such as vasoactive intestinal polypeptide, which is known to be released from parasympathetic terminals. The same mechanism might augment vasodilatation during attacks of cluster headache. PMID- 1422798 TI - Processing of spatial contrast in peripheral vision in Parkinson's disease. AB - Two experiments were carried out to test the hypothesis, based on anatomical evidence, that contrast gain might be reduced in the retinal periphery in Parkinson's disease. In the first experiment, subjects set contrast thresholds before and after adaptation to a vertical grating of 2 cycles per degree (c/deg), either stationary or oscillating sideways through its spatial period at 8 Hz, presented either in central vision or 7 degrees peripherally. Threshold elevations were similar for central viewing in both patients and controls. However, for peripheral viewing, elevations were greater in the controls, but smaller in the patients, than for central viewing. In the second experiment, a staircase procedure was used to find the contrast of a peripherally viewed grating of either 4 or 1.2 c/deg which apparently matched that of a centrally viewed grating of the same spatial frequency. Patients needed more contrast (about 1.6 times, at both spatial frequencies) than controls for a match. These results suggest that contrast gain may be lowered in the peripheral retina in Parkinson's disease, perhaps because of an abnormality of dopamine amacrine cells, whose density peaks in the peripheral retina. PMID- 1422799 TI - Sequential arm movements in patients with Parkinson's disease, Huntington's disease and dystonia. AB - We studied the performance of sequential arm movements in 14 patients with Parkinson's disease, nine patients with Huntington's disease and seven patients with arm dystonia. The results were compared with those from normal subjects. Subjects had to perform each movement of the sequence as fast as possible, stopping as briefly as possible between two successive movements. In one set of experiments, patients with Parkinson's disease drew four different geometrical patterns in a counter-clockwise direction. The patterns consisted of two, three, four and five segments of identical length. In a second set, the subjects drew a pentagon in a counter-clockwise and a clockwise direction and each side of the pentagon singly in a counter-clockwise direction. All three groups of patients were slow in executing movements and in switching from one movement to the next. Only patients with Parkinson's disease took longer to perform the segments at the end of a sequence. In other words, their movement times lengthened progressively as the sequence progressed. This phenomenon could still be recognized when the direction and position of the segments were changed (pentagon drawn in the counter-clockwise and the clockwise direction) and when the extra-time needed, mainly due to the sequential nature of the task, was considered by computing the differences between movement times obtained during drawing of the pentagon and those obtained when each segment was traced singly. This study demonstrates that sequential movements are abnormal in Parkinson's disease, Huntington's disease and dystonia and that in the performance of long motor sequences, the deficit in sequencing movements is exacerbated only in patients with Parkinson's disease. PMID- 1422800 TI - Anodal and cathodal stimulation of the upper-limb area of the human motor cortex. AB - In 18 neurologically normal subjects the corticofugal volleys evoked by anodal and cathodal electrical stimulation of the motor cortex were recorded using epidural electrodes at the high-thoracic and low-thoracic regions of the spinal cord during surgery for scoliosis. At and just above threshold, anodal and cathodal stimulation of the upper-limb area and motor cortex produced a D wave that propagated to the low-thoracic region. The stimulus intensity required to produce D waves was significantly lower with anodal stimulation. I waves were recorded at higher stimulus intensities than the D wave but not more readily with cathodal stimulation. There was no significant difference in the extent to which stimulus intensity had to be increased above D-wave threshold to produce I waves with the two stimulus polarities, and the number of I waves was the same when the stimulus was increased by the same amount above D-wave threshold. After withdrawal of isoflurane, I waves could not be recorded when the stimulus intensity was below D-wave threshold with either stimulus polarity. Anodal stimulation over the upper-limb area remained more effective than cathodal stimulation in producing both D and I waves. These results indicate that, at threshold, regardless of anaesthesia, anodal and cathodal stimuli access upper limb corticospinal neurons directly at a similar site, the anodal stimuli being more effective. In addition, the results suggest that some corticospinal neurons in the upper-limb area of motor cortex have projections to lumbar segments. PMID- 1422801 TI - Seizures involving secondary sensory and related areas. AB - Five patients with seizures involving the secondary sensory and/or related areas (SSRA) are presented. Four of five experienced ictal numbness and/or tingling bilaterally and/or axially; this involved fingertips (three patients), lips (two), tongue (two), and was diffuse in one. The fifth patient experienced bilateral ictal pain. Associated ictal symptoms implicating adjacent regions appeared in all five patients, including contralateral clonic movements (two patients), hypersalivation (two), taste (one), vocalization (two), dysphagia (one), and contralateral sensory march (one). Two patients had ictal symptoms suggestive of adjacent temporal lobe involvement. By history, the SSRA was involved at seizure onset in four and by spread in one. All five patients had electroencephalogram (EEG) or subdural EEG supportive evidence of SSRA involvement: ictal (three) and interictal (three). Three patients had lesions in this area shown by magnetic resonance imaging or computerized tomography and all three had histologically proven glial tumours. Relevant experimental physiological and anatomical data are reviewed. PMID- 1422802 TI - Morphometry of the Sylvian fissure and the corpus callosum, with emphasis on sex differences. AB - The relationship between anatomical asymmetries in the perisylvian region and the sizes of different regions of the corpus callosum was investigated post-mortem in 40 brains of right-handed hospital admissions (20 males, 20 females) with no cortical involvement. There were no sex differences either in anatomical asymmetries or in regional size of the callosum. There was a negative correlation between the absolute value of Sylvian fissure (planum temporale) asymmetries and the size of the isthmus in males but not in females. Further, there was a significant negative correlation between the size of the Sylvian fissure (or planum temporale) and the size of the callosal mid-body in males but not in females. There was no correlation between the asymmetry of the planum temporale magnitude of left-right and total size of the planum (left+right). These findings constrain theories about the ontogenesis of hemispheric specialization through changes in callosal connectivity and about sex differences in interhemispheric organization. PMID- 1422803 TI - Changes in brain functional connectivity in Alzheimer-type and multi-infarct dementia. AB - Clinical and neuropathological evaluation of elderly subjects with dementia has traditionally concentrated upon the focal distribution of brain disease, ignoring changes in the complex connections that link brain areas and that are crucial for cognition. We examined subjects with the two most common forms of dementia in the elderly (dementia of the Alzheimer type or DAT, and multi-infarct dementia or MID); and used electroencephalographic (EEG) coherence to examine the effects of these illnesses on the functional connections between brain areas. We studied coherence between brain areas known to be linked by two different types of connections: (i) dense narrow bands of long corticocortical fibres; (ii) broad complex networks of corticocortical and corticosubcortical fibres. Areas that were linked by dense narrow bands of long corticocortical fibres showed greatly diminished coherence in subjects with DAT; among MID subjects, this coherence was not significantly affected. Areas that were linked by broad connective networks showed the largest decreases in coherence among MID subjects. These findings are consistent with neuropathological evidence that Alzheimer's disease is a neocortical 'disconnection syndrome' in which there is a loss of structural and functional integrity of long corticocortical tracts. The findings further suggest that the vascular disease of MID most prominently affects broad fibre networks that may be more vulnerable to diffuse subcortical vascular damage. A ratio of coherence from complex corticocortical-corticosubcortical networks divided by coherence from long corticocortical tracts correctly classified 76% of subjects into DAT and MID categories. Overall, these results indicate that EEG coherence detects basic pathophysiological differences between subjects with DAT and MID, and that these differences may be clinically useful. PMID- 1422804 TI - A critical appraisal of neuropsychological correlates of Japanese ideogram (kanji) and phonogram (kana) reading. AB - Owing to the Japanese language's unique writing system, which consists of phonograms and ideograms, reading impairments of Japanese brain-damaged patients have attracted the interest of many researchers. Past case reports as well as some widely accepted handbooks and textbooks have concluded that a specific aphasia type or lesion site is associated with a particular impairment pattern of phonograms and ideograms in reading. However, the methodology and analytical procedures in previous studies were inadequate for reliable generalizations to be made. First, the test materials were unspecified or inappropriate, or the number of test items was small. Secondly, the conclusions were presented without providing individual performance data to support them. Thirdly, in associating patterns of reading impairment with lesion sites, only single cases were reported. The present investigation was designed to overcome the omissions of previous studies, and examined the ability to read 46 single phonograms and 46 single ideograms aloud in four groups of sufficiently large numbers of patients; namely, seven pure alexics, 23 Broca aphasics, 13 Wernicke aphasics, and seven patients with alexia and agraphia. Ours are the first data to demonstrate unequivocally no consistent linkage between aphasia type and the patterns of impairment of phonogram and ideogram reading. The impairment patterns were not uniform across patients even in the same aphasia group. A majority of the cases in each group showed that phonograms and ideograms were unselectively impaired. However, ideogram reading was more difficult in three cases in the pure alexia and Broca aphasia groups, respectively, and in one case in the Wernicke aphasia group. Phonogram reading was more severely disturbed in four cases among the Broca aphasics and in one case among the patients with alexia with agraphia. An apparent variability of impairment patterns characterized the Broca aphasic group. These dyslexic patterns did not appear to correlate with the site and extent of lesions identified by computerized tomography scans. Past reports linking a particular impairment pattern of phonogram and ideogram reading and a specific lesion site were studies of single cases, and their conclusions seem oversimplified. While sensory and motor dysfunctions can usually be neuroanatomically localized in individuals, impairments of certain high cortical functions, such as the reading of phonograms and ideograms, may not be correlated with damage to definite neuroanatomical structures. PMID- 1422805 TI - The influence of handedness on the distribution of muscular weakness of the arm in facioscapulohumeral muscular dystrophy. AB - The strength of 10 muscle groups in both arms was measured using hand-held myometry to determine the influence of handedness on left-right differences of muscle strength in facioscapulohumeral muscular dystrophy (FSHD). Two groups of subjects were studied: 24 healthy volunteers (19 right-handed), and 53 patients (42 right-handed) with autosomal dominant FSHD. An opposite left-right difference of strength of shoulder and arm muscles was found: right-handed volunteers were stronger on the right side, right-handed patients were stronger on the left side. This opposite left-right difference was statistically significant for the supraspinatus muscle, the wrist extensors and the shoulder internal rotators. The number of left-handed subjects was too small for statistical analysis. The relation between handedness and increased muscle weakness in right-handed FSHD patients suggests that mechanical factors may play a distinct role in the progression of muscle weakness in FSHD. PMID- 1422806 TI - The evolution of neural circuits controlling feeding behavior in frogs. AB - Our approach to understanding motor systems is a phylogenetic, 'outside-in' approach, the goal of which is to identify behavioral transitions during phylogenesis and elucidate their neurological basis. In this paper, we review the results of recent behavioral, biomechanical and neurological studies on frog feeding behavior. These studies show that highly protrusible tongues have evolved numerous times independently among frogs, and that the biomechanics and neuromuscular control of feeding behavior have been transformed repeatedly during frog evolution. Many of the independent lineages possess unique biomechanical mechanisms for protracting their tongues and unique neural mechanisms for coordinating feeding behavior. In frogs, there has been considerable evolution at the interface between reticular central pattern generators (CPGs) associated with feeding and sensory feedback circuits that modulate feeding motor output. In particular, the roles of hypoglossal and glossopharyngeal sensory feedback appear to have been relatively plastic in their evolution. Prey-type dependence of hypoglossal sensory feedback in Rana suggests that the interaction between descending visual control and sensory feedback also may be evolutionarily plastic. Comparative studies have found that motor systems sometimes evolve conservatively across morphological and behavioral transitions (i.e., the shoulder in birds) or, alternatively, they may be subject to considerably more evolutionary change than is reflected in morphological characteristics (i.e., feeding in cichlids). We hypothesize that the CPG circuits for feeding behavior in the reticular formation may evolve conservatively because they are highly integrated, multifunctional networks which cannot be optimized for one function without compromising others. In contrast, the interfaces between the CPG, sensory feedback and descending control should be less constrained. When changes in motor patterns occur during evolution, it is likely that sensory feedback or descending control may be involved. PMID- 1422807 TI - Chromatophore systems in teleosts and cephalopods: a levels oriented analysis of convergent systems. AB - The neural control of chromatophore display in cephalopod mollusks and teleost fishes is reviewed in the context of convergence of functional-anatomical pathways and mechanisms at several levels of organization. The effector elements or chromatophores are different in origin and design in the two groups of animals. Major functional differences appear to be in the speed of response (greatest in cephalopods) and the magnitude of non-neural control mechanisms (greatest in teleosts). Despite the differences, the elements demonstrate striking overall functional similarity. Elements of different types form highly organized array patterns of similar general complexity. Innervation patterns in cephalopods and teleosts seem comparable, with control being unidirectional (albeit in opposite directions); some elements demonstrate polyaxonal innervation. Motor units in both groups are generally composed of many chromatophores. Packard's concept of 'cronological units' of similar age-classes of chromatophores being innervated by similar age-classes of motor neurons greatly simplifies the understanding of relationships between the static arrays and the physiological units that utilize them to produce chromatic displays. The lower motor control areas for both groups have been grossly identified. Chromatomotor neurons in cephalopods are mostly located in the chromatophore lobes of the subesophageal brain while comparable systems in teleosts are situated in sympathetic chain ganglia (preganglionics) and the rostral spinal cord (postganglionics). Chromatic components are the simplest visually detectable units of color display, e.g. vertical bands and fin spots. They combine to form more complex chromatic patterns, which, in turn, are integrated with components of skin texture, posture and movement to produce display behaviors. Complexity of such systems seems to be of the same order of magnitude in both cephalopods and teleosts. Areas of the CNS related to each of the categorical levels have not been clearly defined. Crude patterning may take place in the basal and, perhaps, peduncle lobes in cephalopods and in the lower and intermediate medulla in teleosts. In both groups, higher level control relates to areas involved in sensorimotor integration and mediation of agonistic, sexual, and, perhaps, other types of behavior: the peduncle and optic lobes in cephalopods and the hypothalamus, tegmentum, otic tectum, torus semicircularis, thalamus and telencephalon in fishes. The systems appear to parallel each other in being organized hierarchically, with similar levels of complexity. Some of the regions may be especially important for regulating color patterns in response to visual input. Overall, chromatomotor control systems in cephalopods and teleosts demonstrate many apparent convergent features. Possible factors responsible for the similarities are discussed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1422808 TI - Muscle architecture and control demands. AB - Muscles effect locomotion, and their gross architecture still poses analytical problems. These problems involve the arrangement of myofibers and motor units within muscles and that of muscles around joints. The arrangement of fibers may involve a range of considerations from the equivalence or nonequivalence of sarcomeres to placement, attachment, and angulation of fascicles and entire muscles; consequently, these levels and their development and coordination overlap. Many problems at the macroscopic level require clarification of how an animal uses a compartment of suite of muscles and whether morphological differences reflect functional ones. The understanding of intermediate architecture, including issues of compartmentation, pinnation, and concatenation, remains more elusive, as some morphologically distinct muscles may be functionally equivalent. As yet we have inadequate appreciation of the opportunities or limitations provided to the control system by a particular arrangement of fibers, or vice versa. Exploration of the rules that govern these conditions provides abundant opportunities for cooperation among neurobiologists, developmental biologists, physiologists and morphologists. PMID- 1422809 TI - The spinal motor system in early vertebrates and some of its evolutionary changes. AB - Recent studies of the spinal motor systems of vertebrates allow us to begin to infer the organization of the motor apparatus of primitive vertebrates. This paper attempts to define some of the features of the motor system of early vertebrates based on studies of the motor systems in anamniotes and in Branchiostoma. It also deals with some changes in the primitive motor system during evolution. The primitive motor system consisted of myomeric axial muscles, with a functional subdivision of the musculature into non-spiking slow muscle fibers segregated in the myomeres from spiking fast ones. These fibers were innervated by two major classes of motoneurons in the cord-large motoneurons innervating faster fibers and small motoneurons innervating slow fibers. There was not a simple isomorphic mapping of the position of motoneurons in the motor column onto the location of the muscle fibers they innervated in the myomeres. Early vertebrates used these axial muscles to bend the body, and the different types of muscle fibers and motoneurons reflect the ability to produce slow swimming movements as well as very rapid bending associated with fast swimming or escapes. The premotor network producing bending was most likely a circuit composed of a class of descending interneurons (DIs) that provided excitation of ipsilateral motoneurons and other interneurons, and inhibitory commissural interneurons (CIs) that blocked contralateral activity and played an important role in generating the rhythmic alternating bending during swimming. This DI/CI network was retained in living anamniotes. At least two major descending systems linked the sensory systems in the head to these premotor networks in the spinal cord. The ability to turn on swimming by activation of DI/CI premotor networks in the cord resided at least in part in a midbrain locomotor region (MLR) that influenced spinal networks via projections to the reticular formation. Reticulospinal neurons were important not only for initiation of rhythmic swimming but also in the production of turning movements. The reticulospinal cells involved in turns produced their effects in part via monosynaptic connections with motor neurons and premotor interneurons, including some involved in rhythmic swimming. A prominent and powerful Mauthner cell was most likely present and important for rapid escape or startle movements. Some features of this primitive motor apparatus were conserved during the evolution of vertebrate motor systems, and others changed substantially. Many features of the early motor system were retained in living anamniotes; major changes occur among amniotes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1422810 TI - Brainstem control of orienting movements: intrinsic coordinate systems and underlying circuitry. AB - A fundamental issue in the understanding of how the nervous system processes information is the way in which sensory information is used to initiate and guide movements. Recent progress has been made by taking an information processing approach in which information--for example, the spatial location of an object towards which an animal will orient--is tracked through the nervous system from sensory to motor levels. In this approach, neurally encoded information is characterized in terms of its representation within a neural or intrinsic coordinate system or set of neural coding parameters. For example, the retina codes spatial location in terms of the location of activity on the retinal surface, whereas motoneurons code spatial location in terms of the pulling directions of the muscles they activate. In between these two peripheral stages, the information passes through intermediate coordinate systems. These intermediate coordinate systems can be characterized by recording or altering the activity of small groups of neurons while an animal is performing a well-defined sensorimotor task. Spatial location information is used to guide orienting movements, those movements made by the eyes, ears, head, or body which function to center an object of interest in the animal's visual field. The optic tectum and forebrain, their connections to the medial mesencephalic and rhombencephalic brainstem tegmental cell groups, and subsequent connections to brainstem motor nuclei and spinal cord are employed to control fundamental aspects of this behavior. Studies reviewed herein indicate that following the retinotopic coding of spatial location in the retina and tectum, spatial location information appears to enter a different coordinate system at tegmental levels in which spatial aspects of orienting movement are coded in terms of their discrete horizontal and vertical components. This Cartesian coordinate system is an example of an abstract neural coordinate system, in that it is a simple, low dimensional representation of spatial location which differs greatly from both sensory and motor representations. Also, this Cartesian representation may be common to many orienting movements, yet it appears to differ from the coordinate systems controlling other movement types such as stabilization or phasic movements. This suggests an hypothesis in which coordinate systems, especially at intermediate levels of processing, may be organized according to behavioral task as opposed to being determined by the particular sensory or motor system involved in the behavior. Understanding the evolutionary heritage and computational function of abstract neural coordinate systems, and the relation between different coordinate systems and behavioral tasks may be useful in understanding general aspects of sensory information processing and motor control. PMID- 1422811 TI - p75 nerve growth factor receptor immunoreactivity in the human brainstem and spinal cord. AB - The distribution of nerve growth factor receptor (NGFR) immunoreactive profiles was investigated in the adult human brainstem and spinal cord using a monoclonal antibody directed against the primate low affinity (p75) NGFR. In the human brainstem, p75NGFR immunoreactive profiles were seen within the mesencephalic and descending nucleus of the trigeminal nerve, the nucleus and tractus solitarius, glossopharyngeal nerve, hypoglossal nucleus, nucleus subtrigeminalis, subnucleus ventralis of the central nucleus of the medulla, nucleus cuneatus and gracilis. At the level of the upper cervical spinal cord, p75NGFR immunoreactive profiles were also seen within the incoming dorsal roots, zone of Lissauer and substantia gelatanosa (lamina II). Virtually no immunoreactivity was associated with cervical spinal cord motor neurons. The demonstration of the p75NGFR in brainstem and spinal cord regions associated with the central transmission of peripheral sensory information suggests that these systems may be influenced by the trophic substance nerve growth factor. PMID- 1422812 TI - VIP-like immunoreactivity in the suprachiasmatic nuclei of a mutant anophthalmic mouse. AB - The suprachiasmatic nuclei (SCN) of mutant anophthalmic (strain ZRDCT-An) and sighted control mice was examined using light microscopic methods for cytoarchitecture and immunocytochemistry for vasoactive intestinal polypeptide (VIP). The SCN of the anophthalmic mice were asymmetrical, and quite variable in cytoarchitecture. Immunocytochemistry for VIP revealed strong staining of cells and fibers. Within the SCN, the distribution of VIP-immunoreactive cells was more diffuse in anophthalmic mice than in the controls; immunoreactive neurons were frequently observed in ectopic locations in the mutant animals. PMID- 1422813 TI - The specific N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocks U 50,488, but not morphine antinociception. AB - The effect of the specific NMDA receptor antagonist MK-801 on antinociception produced by the kappa opiate receptor agonist U-50,488 and the mu receptor agonist morphine was assessed using the tail-flick test in rats. MK-801 (0.05 and 0.1 mg/kg) antagonized antinociception induced by all three doses of U-50,488 (7.5, 15 and 30 mg/kg), and potentiated antinociception induced by the lower (1 mg/kg) but not higher (5 mg/kg) dose of morphine. Naloxone at a dose of 1.0 but not 0.1 mg/kg blocked U-50,488 antinociception, indicating that MK-801 affects opiate antinociception. The present results are the first to suggest a critical role for the NMDA receptor in opiate antinociception involving the kappa receptor. PMID- 1422814 TI - Electrophysiology of nitrous oxide on cerebellar granule cells: a single-cell study. AB - We recorded 18 single cells in the granule cell layer of the cat. Each single cell was screened and identified as a granule cell based on a set of criteria derived from known electrophysiological properties of granule cells. We then monitored the effects of nitrous oxide on the spontaneous activities and the auditory responses of these cells. Nitrous oxide consistently caused a severe inhibition of spontaneous activities as well as responses to sound in these cells. Furthermore, the amplitudes of their action potentials decreased during the inhibition. Three of the 18 cells were subsequently injected intracellularly with HRP. All three were verified to be granule cells. In those granule cells we recorded intracellularly, nitrous oxide did not change the resting membrane potentials. The gradual decrease in the amplitudes of action potentials suggested that some of the mechanisms leading to the genesis of action potentials were being altered by nitrous oxide. It is also possible that nitrous oxide may act on synaptic transmission at a site located postsynaptically on the granule cells. PMID- 1422815 TI - Release of gamma-aminobutyric acid by visual stimulation in the kitten visual cortex. AB - Release of gamma-aminobutyric acid (GABA) was measured by brain microdialysis and high-performance liquid chromatography (HPLC) in the visual cortex of anesthetized kitten. The basal level of endogenous GABA release was 0.25 +/- 0.02 pmol/30 microliters dialysate (n = 8), which was near the lower limit of resolution of the present measuring system. When nipecotic acid, a GABA uptake inhibitor, was infused, release was increased 5-10 fold. The nipecotic acid induced GABA output was not affected by the infusion of tetrodotoxin (TTX), a sodium channel blocker. Visual stimulation presented to one eye led to a marked increase in GABA output over the basal level. This effect was completely suppressed by TTX administration. These results suggest that the increase in GABA output in response to visual stimulation is due to an increase in GABAergic neuronal activity in the kitten visual cortex. PMID- 1422816 TI - Peripheral origin of olfactory nerve fibers by-passing the olfactory bulb in Xenopus laevis. AB - After DiI injections into the diencephalon of Xenopus, two types of retrogradely labelled cells were found in the nasal area: (i) receptor cells in the olfactory epithelium and (ii) a small cell group located between the main olfactory epithelium and the vomeronasal system. These results reveal an extensive extrabulbar olfactory projection of olfactory receptor cells. Fibers of these cells do not terminate in the olfactory bulb but innervate targets in the diencephalon directly. The other type of retrogradely labelled cells, apparently, are not part of any epithelium. They resemble similar cell groups which have previously been regarded as part of the nervus terminalis system in other vertebrates. PMID- 1422817 TI - Hippocampal mossy fiber distribution does not correlate with two-way active avoidance performance in backcross lines derived from inbred mouse strains DBA/2 and C3H. AB - To elucidate the relation of genetically induced variations in two-way active avoidance performance and the extent of the hippocampal infra/intrapyramidal mossy fiber system (IIP-Mf) in inbred mouse strains DBA/2 (high performance, small IIP-Mf) and C3H (low performance, large IIP-Mf) we investigated a backcross line containing the DBA/2-derived genetic determinants for high avoidance performance in a C3H background. In the seventh backcross generation variations in performance analogous to the original strains were observed whereas the extent of mossy fibers was nearly homogeneous. This result suggests that both variables are determined by separate genetic factors at least in these strains and that differences in mossy fiber distribution are not an essential prerequisite for different active avoidance performance. PMID- 1422818 TI - Olfactory ensheathing cells myelinate dorsal root ganglion neurites. AB - The objective of this study was to determine whether olfactory ensheathing cells (from E18 rat embryos) could myelinate dorsal root ganglion neurites in vitro. By four weeks many of the S100-positive ensheathing cells were Gal-C+ and MBP+ and had begun to myelinate the larger axons, as visualized with the electron microscope. We conclude that olfactory ensheathing cells can form a myelin sheath if given the opportunity to ensheath neurites of a proper size. PMID- 1422819 TI - Parvalbumin and calbindin D-28K in the human entorhinal cortex. An immunohistochemical study. AB - Research is here reported on the distribution of immunoreactivities of the calcium-binding proteins parvalbumin and calbindin D-28K in the entorhinal cortex of normal human brains. Topographically, parvalbumin immunoreactive neurons were only seen in the lateral portion of the rostral entorhinal cortex, in continuity with the adjacent perirhinal cortex. The intermediate and caudal portions gave positive results along the mediolateral extension of the entorhinal cortex. The laminar distribution of parvalbumin immunoreactive neurons was similar throughout the entorhinal cortex. Heavy immunostaining, largely coincident with cell islands, was observed in cells and fibers in layer II, being densest in the deep half of layer III and more sparsely distributed in layers V and VI. Calbindin D 28K immunoreactivity was found throughout the entorhinal cortex. In contrast to parvalbumin immunoreactivity, calbindin D-28K was present from layer I up to upper layer III, the neurons being most numerous in the cell islands of layer II. These results show that rostromedial portions of the human entorhinal cortex contain calbindin immunoreactivity, but not parvalbumin, while the lateral, intermediate and caudal portions of the entorhinal cortex contain both calcium binding proteins. As it is known that these two proteins belong to a subset of GABAergic neurons, we suggest that a topographical diversity in some of the cells may be responsible for inhibitory effects in the human entorhinal cortex. This proposed diversity might be relevant to the processing of information that the entorhinal cortex conveys to the dentate gyrus and receives from various components of the hippocampus, the subicular complex and other cortical and subcortical sources. PMID- 1422820 TI - The basis and functional role of the late EMG activity in human forearm muscles following wrist displacement. AB - The present paper examines the hypothesis that the long latency EMG activity produced by muscle stretch is the result of long loop reflex pathways involved in the control of limb stiffness. We recorded the cerebral responses and late EMG activity in agonist and antagonist muscles following sudden stretch of the wrist extensor muscles under 4 experimental conditions in 11 subjects. In each experiment subjects held their right wrist extended isometrically against a constant force of 2.3 N and a trial was begun with a step increase in the force from 2.3 N to 18.4 N, to stretch the extensor muscle. In the first and second experiments the force change occurred unpredictably and subjects had to either oppose the perturbation (Unpredictable Oppose) or relax the forearm muscles once the increase in force was detected (Unpredictable Let-Go). In the third and fourth experiments the force change occurred predictably when subjects pressed a thumb switch with the left hand to cause it. As before, subjects were instructed to either oppose the perturbation (Predictable Oppose) or relax the forearm muscles (Predictable Let-Go). Responses were recorded from the flexor and extensor carpi radialis muscles and from the scalp. When the perturbing force occurred unpredictably, early latency EMG activity (the MI response) was seen in the stretched extensor muscle, and longer latency EMG activity was seen simultaneously in both extensor and flexor muscles. When the force change occurred predictably the late EMG activity was considerably attenuated, especially in the Predictable Let-Go condition. Cerebral responses similarly depended upon the predictability of the perturbation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422821 TI - Subcellular distribution of serotonin in the lamprey spinal cord. AB - The subcellular distribution of serotonin (5-hydroxytryptamine; 5-HT) in the lamprey (Ichtyomyzon unicuspis, Lampetra fluviatilis) spinal cord was investigated by using ultracentrifugation on continuous density gradients combined with an electron microscopic analysis of the gradients and of immunostained tissue. Endogenous 5-HT was analyzed by high-performance liquid chromatography with electrochemical detection. After differential centrifugation, the highest levels of 5-HT were found in the particulate fractions. After ultracentrifugation of lysed synaptosomal fractions on continuous sucrose gradients and the subsequent sedimentation of the individual fractions, 5-HT showed a biphasic distribution in the gradient. The two peaks corresponded to 0.30-0.40 M and 0.85-1.05 M sucrose. Electron microscopy of intact tissue showed that some of the boutons were strongly immunoreactive to 5-HT with dense precipitates over large granular vesicles. The area around these large vesicles, however, also showed reaction product. Large granular vesicles could be clearly distinguished in the immunostained axonal varicosities. In tissue not processed for 5-HT immunoreactivity it was seen that the varicosities contained not only large dense-cored vesicles, but also small agranular vesicles. An electron microscopical analysis of the subcellular fractions revealed that the fraction corresponding to the "light" 5-HT peak contained numerous vesicular structures, which in most cases were electron lucent. In the "heavy" fractions, nerve ending particles containing vesicles of various sizes were observed. The results suggest that 5-HT in the lamprey spinal cord may be distributed in more than one subcellular compartment which, apart from the cytosol, possibly corresponds to small and large synaptic vesicles. PMID- 1422822 TI - N-methyl-D-aspartate unilaterally injected into the dorsal striatum of rats produces contralateral circling: antagonism by 2-amino-7-phosphonoheptanoic acid and cis-flupenthixol. AB - To evaluate the possible contribution of dorsal striatal glutamate receptors to motor behavior, circling responses were observed in rats following unilateral intrastriatal microinjections of the agonist, N-methyl-D-aspartate (NMDA) or the antagonist, 2-amino-7-phosphonoheptanoic acid (APH). The role of dopamine (DA) in NMDA-produced circling also was evaluated. In experiment 1, an NMDA dose of 5.0 micrograms (in 0.5 microliter), but not 0.5 or 0.05 microgram produced significant contraversive circling. In experiment 2, an APH dose of 10.0 micrograms but not 1.0 or 0.1 microgram produced significant ipsiversive circling. In experiment 3, microinjection of the ineffective 0.1 microgram dose of APH or a dose (20 micrograms) of the DA antagonist, cis-flupenthixol, that did not produce circling when administered alone, significantly reduced the circling response produced by the 5.0 micrograms dose of NMDA. As NMDA produced circling in the same direction as that seen following similar unilateral injections of locomotion-stimulating DA agonists, the present results suggest that glutamate, acting via NMDA receptors in the dorsal striatum, may exert an excitatory influence on motor systems. The observation that a DA receptor blocker antagonized the NMDA response further suggests that the observed motor excitatory effect of glutamate at NMDA receptors requires concurrent stimulation of DA receptors in the same region of the striatum. PMID- 1422823 TI - 5-Hydroxytryptamine-3 receptors modulate synaptic activity in the rat nucleus tractus solitarius in vitro. AB - Whole-cell patch clamp recordings were made from neurons in the rat nucleus tractus solitarius (NTS) in transverse brainstem slices. 5-Hydroxytryptamine (5 HT, 100 microM) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-CH3-5 HT, 100 microM) depolarized 86% of NTS neurons at resting membrane potential (Vm). This response was resistant to tetrodotoxin (TTX) and Co2+ application. In addition, 2-CH3-5-HT (500 nM-100 microM) increased the amplitude and frequency of both excitatory and inhibitory spontaneous synaptic potentials. This effect was also TTX-resistant, but was abolished by Co2+. The effects of 2-CH3-5-HT on EPSPs and IPSPs evoked by electrical stimulation of the tractus solitarius (TS) were analyzed separately in the presence of bicuculline or 6-cyano-7-nitroquinoxaline 2,3-dione (CNQX), respectively. Concentrations of 2-CH3-5-HT between 500 nM and 1 microM decreased the amplitude of evoked EPSPs and IPSPs with similar potency. The selective 5-HT3 receptor antagonists ICS 205-930 (10 nM) and MDL 72222 (10 microM) reversibly blocked the effects of 2-CH3-5-HT at all doses examined. It is concluded that 5-HT3 receptors can mediate both pre- and postsynaptic responses in the NTS. PMID- 1422824 TI - Responses of globus pallidus neurons to cortical stimulation: intracellular study in the rat. AB - The responses of globus pallidus (GP) neurons to stimulation of the sensorimotor cortex, the neostriatum, and the subthalamic nucleus were intracellularly recorded in anesthetized rats. Stimulation of the cortex evoked a sequence of postsynaptic responses including an initial short EPSP, a short IPSP, and a late EPSP with multiple spikes in most of the repetitively firing GP neurons. The response pattern was very similar to those evoked by striatal stimulation, except that the latencies were longer. An acute knife cut placed immediately caudal to the substantia nigra caused no significant change in the responses to cortical and striatal stimulation. Stimulation of the subthalamic nucleus evoked a short latency EPSP overlapped with an IPSP. The polarity of all the IPSPs was reversed by a Cl- injection. A systemic injection of picrotoxin abolished all the IPSPs and unmasked large depolarizations with multiple spikes. An ibotenic acid lesion of the subthalamic nucleus eliminated both the initial short latency and late EPSPs to cortical and striatal stimulation and disclosed a prominent IPSP. Stimulation of the lesioned subthalamic nucleus also evoked large, short latency IPSPs without noticeable EPSPs. These results indicate that (i) the IPSPs evoked by cortical, striatal, and subthalamic stimulation were mediated by a GABAA receptor, (ii) both the initial and late EPSPs to cortical and striatal stimulation involved activation of the subthalamic nucleus but not brainstem nuclei, and (iii) cortically derived signals mediated through the neostriatum (i.e. long latency IPSPs) and the subthalamic nucleus (i.e. short latency EPSPs) converged on most GP neurons. PMID- 1422825 TI - Noradrenergic activation in the paraventricular nucleus during acute and chronic immobilization stress in rats: an in vivo microdialysis study. AB - In vivo microdialysis was used to study the effects of single (2 h) or repeated (2 h for 7 consecutive days) immobilization (IMMO) stress on extracellular fluid concentrations of norepinephrine (NE) and the deaminated metabolites of NE and dopamine, dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) in the paraventricular nucleus of conscious rats. During IMMO, NE, DHPG, and DOPAC levels increased markedly, with similar peak values and time courses in the repeatedly stressed and previously unstressed groups. NE levels during a 2-h baseline period were lower in the repeatedly stressed group than in the unstressed group (99 +/- 9 pg/ml vs. 167 +/- 13 pg/ml, P less than 0.05), whereas DHPG (1,697 +/- 263 pg/ml vs. 1,424 +/- 194 pg/ml) and DOPAC (5,989 +/- 863 pg/ml vs. 4,428 +/- 1150 pg/ml) levels tended to be higher, so that the NE/DHPG ratio at baseline was significantly lower in the repeatedly stressed group (P less than 0.05). The results indicate that IMMO stress enhances NE release, reuptake, metabolism, and synthesis in the PVN. Repeated exposure to IMMO may decrease the microdialysate NE/DHPG ratio by inhibiting exocytotic release or enhancing neuronal reuptake of NE. In either case, the results suggest that repeated exposure to stress alters the release and disposition of NE in the PVN of conscious animals. PMID- 1422826 TI - Excitatory effects of thyrotropin-releasing hormone on neurons within the nucleus ambiguus of adult guinea pigs. AB - The electrophysiological effects of thyrotropin-releasing hormone (TRH) on neurons within the nucleus ambiguus (NA) of adult guinea pigs were studied using an in vitro brain stem slice preparation. In 0.01-1.0 micron TRH, NA neurons depolarized (25/39), expressed enhanced postinhibitory rebound (8/8 tested), or exhibited oscillations of the membrane potential (17/39). Because the amplitude of postinhibitory rebound in tetrodotoxin (TTX) at various membrane potentials was not altered by TRH, it suggests that TRH enhanced postinhibitory rebound indirectly by depolarizing the cell membrane. The membrane potential oscillations in NA neurons were persistent in TTX and their frequency was dependent on the membrane potential, suggesting that these oscillations were due to intrinsic membrane properties and not to synaptic inputs. The excitation of NA neurons in vitro by TRH suggests that endogenous TRH may modulate the activity of neurons involved in the regulation of respiratory and autonomic function. PMID- 1422827 TI - Suppression of interictal bursting in hippocampus unleashes seizures in entorhinal cortex: a proepileptic effect of lowering [K+]o and raising [Ca2+]o. AB - The relation between interictal bursts (IIBs) and seizures in epilepsy is obscure. Results from some human and animal studies suggest that IIBs may actually suppress seizure activity. This appears particularly true in the zero magnesium in vitro seizure model. Here we provide new evidence in support of this and new insight into the mechanisms of seizure suppression in this model. Brain slices containing hippocampus and entorhinal cortex were bathed in zero magnesium medium. Electrographic seizures appeared, then were replaced by IIBs. Upon lowering [K+]o and raising [Ca2+]o the IIBs disappeared and the seizures reappeared. Repeated stimuli mimicking IIBs then suppressed seizures again. Selective knife cuts revealed that the IIBs originated in the hippocampus (area CA3) whereas the seizures originated in entorhinal cortex. These results confirm that IIBs suppress seizures in the zero magnesium model. They also show that an important aspect of the interaction between IIBs and seizures in this model is the anatomical segregation of their respective sites of origin. This may apply in other models and in human epilepsy as well. Finally, these results illustrate that one consequence of the anatomical segregation and mutual interaction of IIBs and seizures is that influences which are locally pro- or antiepileptic can have opposite effects in a broader region. PMID- 1422828 TI - Gamma-vinyl GABA prevents hippocampal and substantia nigra reticulata damage in repetitive transient forebrain ischemia. AB - GABAergic inhibitory mechanisms may offer protection to neurons after global ischemia. We tested the effects of gamma-vinyl GABA, a GABA-transaminase inhibitor, via continuous infusion in the third ventricle (Alza pumps) in a gerbil model of repetitive forebrain ischemia. We used two episodes of 3 min duration with a 'reperfusion' interval of 1 h between the insults. Histological analysis was done with silver staining 5 days after the insult. Our results show that there is significant protection of the hippocampus CA1 region and substantia nigra reticulata in treated animals compared to controls. An increase in GABA levels, decrease in glutamate, or mild hypothermia, may be potential mechanisms for this protection. GABAergic agents may prove useful agents in repetitive ischemia. PMID- 1422829 TI - Studies related to the use of colchicine as a neurotoxin in the septohippocampal cholinergic system. AB - Colchicine has been shown to be neurotoxic to cholinergic neurons in the medial septum 1 week following intracerebroventricular injections. The experiments described here were designed to examine the selectivity of this effect over a longer time course, and to examine the role of axoplasmic transport in the neurotoxic effect. As previously reported, 1 week after intracerebroventricular injections of colchicine, the numbers of choline acetyltransferase (ChAT) immunoreactive neurons in the medial septum-diagonal band complex (MSDB) were reduced to 38% of control; this reduction was stable 2 and 3 weeks post injection. Injections of colchicine placed into the body of the fornix produced similar results. GAD-immunoreactive somata, the other major population of neurons in the MSDB, were unaffected 3 weeks following colchicine, as previously reported 1 week following similar injections. The normal AChE staining pattern in the hippocampus, particularly the dentate gyrus, was depleted following either ICV or intrafornical injections of colchicine. This depletion was more severe with longer survival times. Injections of lumicolchicine, an isomer of colchicine which does not bind tubulin, had no effect on ChAT-immunoreactive neurons in the MSDB or on AChE staining in the hippocampus. Injections of colchicine, but not of lumicolchicine, partially blocked the retrograde transport of the fluorescent dye Fluoro-Gold from the hippocampus to the MSDB. In addition, the content of NGF in the hippocampus rose 84% above control values 2 weeks following colchicine and remained elevated at three weeks. Together these results indicate that colchicine is selectively toxic for cholinergic neurons in the septohippocampal system, and suggest that the alkaloid's neurotoxic effects work via the blockade of axoplasmic transport. PMID- 1422830 TI - Electrophysiological effects of MK-801 on rat nigrostriatal and mesoaccumbal dopaminergic neurons. AB - The electrophysiological effects of the non-competitive N-methyl-D-aspartate (NMDA) antagonist (+)-MK-801 (MK-801) on nigrostriatal and mesoaccumbal dopaminergic (DA) neurons were evaluated in chloral hydrate-anesthetized rats. MK 801 (0.05-3.2 mg/kg, i.v.) stimulated the firing rates of 14 (74%) of 19 nigrostriatal DA (NSDA) neurons and all 16 mesoaccumbal DA (MADA) neurons tested. Stimulatory effects of the drug were more prominent on MADA neurons. Interspike interval analysis revealed that MK-801 also regularized DA neuronal firing pattern. Acute brain hemitransection between the midbrain and forebrain attenuated the stimulatory effects of MK-801 on firing rate and blocked the effects on firing pattern. Similar to MK-801, hemitransection itself increased NSDA and MADA cell firing rates and regularized firing pattern. Both i.v. and iontophoretic MK-801 blocked the excitatory effects of iontophoretic NMDA but did not affect excitations caused by the non-NMDA glutamatergic receptor agonists quisqualate and kainate. Iontophoretic MK-801 had no effect alone. These results suggest that the excitatory effects of i.v. MK-801 on DA neuronal activity are not due to direct actions on DA neurons. Glutamatergic projections originating anterior to the hemitransection appear to play a role in the effects of MK-801 on DA neuronal activity. PMID- 1422831 TI - Neurons of the chick brain and retina expressing both alpha-bungarotoxin sensitive and alpha-bungarotoxin-insensitive nicotinic acetylcholine receptors: an immunohistochemical analysis. AB - Immunohistochemical methods were used to study the possible co-localization of two alpha-bungarotoxin-sensitive (alpha 7 and alpha 8) and two alpha-bungarotoxin insensitive (beta 2 and alpha 3) subunits of the nicotinic acetylcholine receptors in neurons of the chick brain and retina. Several structures contained neurons that were doubly-labeled with antibodies against the alpha 7 subunit and the beta 2 subunit. These structures included, for example, the interpeduncular nucleus, nucleus spiriformis lateralis, optic tectum, pretectal visual nuclei, and the lateral hypothalamus. Double-labeling with antibodies against the alpha 7 and alpha 8 subunits was also seen in several regions, which included the interpeduncular nucleus, visual pretectum, lateral hypothalamus, dorsal thalamus, and the habenular complex. In the retina, many cells in the inner nuclear layer were observed to contain alpha 8 and alpha 3 subunits, whereas neurons in the ganglion cell layer were seen to contain alpha 7 and alpha 8 or, less frequently, alpha 7 and alpha 3 subunits. These results indicate that alpha-bungarotoxin sensitive and alpha-bungarotoxin-insensitive subunits of the nicotinic receptors are co-expressed by neurons of the chick brain and retina. PMID- 1422832 TI - Transport, uptake, and metabolism of blood-borne vasopressin by the blood-brain barrier. AB - Transport, binding, and metabolism of [phenylalanyl-3,4,5,-3H(N)]arginine vasopressin (AVP) by the blood-brain barrier (BBB) was studied in adult guinea pigs by means of a novel vascular brain perfusion (VBP)/capillary depletion technique and HPLC. A time-dependent, progressive brain uptake of 3H radioactivity was measured over the 10 min period of VBP both in brain homogenates and in brain tissue depleted of cerebral microvessels. The unidirectional blood-to-brain transport constant, K(IN), estimated by multiple time tissue uptake analysis of the homogenate and postcapillary supernatant, indicated that the BBB transfer rate for [3H]AVP (K(IN) = 2.37 +/- 0.25 microliters min-1 per gram brain homogenate) was almost 10 times higher than for simultaneously perfused [14C]sucrose, a cerebrovascular space marker. In contrast to homogenate and postcapillary supernatant, the [3H]radioactivity determined in the vascular pellet after dextran density centrifugation of the brain homogenate was very low and only somewhat higher than for [14C]sucrose. HPLC analysis of the perfused brain tissue revealed time-dependent degradation of the blood-borne neuropeptide. The percentage of intact [3H]AVP as determined in the postcapillary supernatant progressively declined during brain perfusion, from 49% at 1 min to 11.9% at 10 min. The major detectable labeled metabolite was [3H]phenylalanine, the labeled amino acid residue of [3H]AVP. The aminopeptidase inhibitor bestatin (0.5 mM), perfused simultaneously with [3H]AVP by the VBP technique, did not alter tissue uptake of [3H]AVP, indicating that there was no significant hydrolysis of peptide by the luminal BBB surface.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422833 TI - Effect of subcutaneous administration of the chemical algogen formalin, on 5-HT metabolism in the nucleus raphe magnus and the medullary dorsal horn: a voltammetric study in freely moving rats. AB - The effect of subcutaneous administration of the chemical algogen formalin, on serotonin (5-HT) metabolism in the nucleus raphe magnus (NRM) and the medullary dorsal horn (MDH) has been investigated using in vivo 5-hydroxyindole electrochemical (peak '3') detection with treated, multi-carbon fiber electrodes and differential pulse, or normal pulse, voltammetry in freely moving rats. The subcutaneous (s.c.) injection of 50 microliters of 10% formalin in the left forepaw was followed, at the NRM level, by a significant increase in the voltammograms as compared to controls (50 microliters of saline 0.9% s.c. in left forepaw) for about 70 min after the injection, before a return to control values. At the MDH level, the formalin injection induced no significant effect on peak 3, as compared to controls, during the first 70 min. After that, the voltammograms significantly increased and remained above controls for up to 180 min. Thus, the time-courses of NRM and MDH effects appear markedly different. These findings suggest that, depending on the anatomical level (NRM or MDH) and/or the period of observation, one can measure differences in the time-course of the increase in 5 HT metabolism in the NRM-dorsal horn serotonergic system by tonic noxious stimuli, such as the formalin test. PMID- 1422834 TI - Blood-brain barrier integrity and brain water and electrolytes during hypoxia/hypercapnia and hypotension in newborn piglets. AB - This study examines the effects of hypoxia/hypercapnia and hypoxia/hypercapnia with hypotension (hypotensive-hypoxia/hypercapnia) on blood-to-brain transfer constants (K1) for sodium and mannitol and brain water and electrolyte contents in newborn piglets. Hypoxia/hypercapnia was induced for 60 min with the piglets breathing a gas mixture of 15% carbon dioxide, 10-12% oxygen, and 73-75% nitrogen adjusted to achieve an arterial pH less than 7.15, pO2 less than 40, and pCo2 greater than 60 mmHg and hypotension for 20 min by rapid phlebotomy to achieve a mean arterial blood pressure less than 40 mmHg. Piglets were studied during 1 h of, and 24 h after resuscitation from hypoxia/hypercapnia (arterial pH 6.9 +/- 0.18, pO2 36 +/- 6 mmHg, pCO2 68 +/- 8 mmHg, mean +/- S.D.) and 10 min, and 24 h after resuscitation from hypotensive-hypoxia/hypercapnia (mean arterial blood pressure 28 +/- 10 mmHg, mean +/- S.D.). Values for K1 for sodium and mannitol, measured using the integral technique were 15.9 and 5.2 ml.g-1.min-1 x 10(4) respectively, in 2-4-day-old controls, suggesting that the barrier is fully developed in newborn piglets. Values were not different during or after hypoxia/hypercapnia or 24 h after hypotensive-hypoxia/hypercapnia. Ten to forty min after hypotensive-hypoxia/hypercapnia, there was a proportional decrease in the K1 for sodium and mannitol of about 40%. These results suggest that the newborn piglet is similar to the adult with respect to impermeability of the blood-brain barrier to ions and small molecules and resistance of this barrier to systemic hypoxia/hypercapnia and hypotension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422835 TI - Amastatin potentiates drinking elicited by osmotic stimuli: evidence for peptidergic mediation of intracellular dehydration-induced thirst. AB - Aminopeptidase inhibitors have been demonstrated to enhance the behavioral effects of both exogenously applied and endogenously released neuropeptides. In this study peptidase inhibitors were used as probes for involvement of central neuropeptides in osmotically-induced drinking behavior. Intracerebroventricular (i.c.v.) injections of amastatin, an aminopeptidase A inhibitor, potentiated water intake induced by subcutaneous injections of hypertonic saline. Drinking responses to i.c.v. infusions of hypertonic saline were also enhanced when amastatin was added to the infusions. The effect was not attenuated by the angiotensin receptor antagonist, [Sar1, Thr8]angiotensin II, which suggests that angiotensins do not play a role in the over-drinking. Drinking responses to centrally infused hypertonic saline were not enhanced by i.c.v. thiorphan, an endopeptidase inhibitor; this provides evidence that the effects of amastatin are specific for a particular class of peptidases. These results suggest that there is a role for an endogenous, non-angiotensinergic brain peptide in the mediation of osmotic thirst. PMID- 1422836 TI - Behavioral effects of mouse interferons-alpha and -gamma and human interferon alpha in mice. AB - Behavioral effects of murine interferon-alpha and -gamma were explored using a well-characterized system for detecting interferon effects. In addition, the effectiveness of human interferon-alpha was determined. Mouse gamma-interferon decreased activity and food-related behavior, effects that were similar to the effects of mouse alpha-interferon. Equivalent doses of the human preparation had little effect upon these measures in mice. Some common action of alpha- and gamma interferon is likely responsible for the similar effects seen for the two molecules. Low effectiveness of the human preparation in mice was predicted due to the differences in receptors between species. PMID- 1422837 TI - Pulse jitter retards kindling without affecting brain-stimulation reward. AB - Convulsions in rats bar-pressing for electrical stimulation of the brain can interfere with the behavioural evaluation of the properties of the reward substrate. If seizure activity involves the synchronous activation of populations of neurons, then the regular timing of pulses may be important in epileptogenesis produced by electrical stimulation. In the first experiment we found that behaviourally derived, charge-duration functions collected from three self stimulating rats with lateral hypothalamic electrodes were not affected by introducing a controlled, 50% jitter to the interpulse interval of self stimulation trains. In the second experiment, we kindled two groups of 6 rats with once-daily, 1.0 s bursts of either regularly timed or jittered pulses to the amygdala until full motor seizures developed. Although both groups eventually attained Class 5 convulsions, the time to first seizure was about two days longer with jittered pulses. Thus, while the circuitry that accumulates input from self stimulation is not affected by the irregularity of asynchronous pulses, the jitter does seem to retard the development of seizures. PMID- 1422838 TI - Subthalamic nucleus cell firing in the 6-OHDA-treated rat: basal activity and response to haloperidol. AB - Single unit recordings from neurons of the subthalamic nucleus were made in control and 6-hydroxydopamine (6-OHDA)-treated rats anesthetized with chloral hydrate. Subthalamic nucleus cells in this preparation exhibited a wide range of firing rates and three different firing patterns. These patterns were defined as 'burst', 'normal', and 'mixed' based on comparisons of their interspike interval histograms. Four to 6 weeks after 6-OHDA treatment there was no change in the basal firing rates of subthalamic nucleus cells, but there was a significant shift in firing pattern, with a smaller proportion of cells exhibiting the 'normal' firing pattern. The response of subthalamic nucleus neurons to acute administration of haloperidol was also altered in 6-OHDA-treated rats tested 4-6 weeks post-lesion, with a significantly greater proportion of cells responding to doses of haloperidol as low as 0.2 mg/kg (i.v.) with increases in firing rate of 20% or more. These results suggest that the subthalamic nucleus is probably not involved in the increases in basal levels of dopamine cell activity observed previously in the 6-OHDA-treated rat, but may play a role in the acute induction of depolarization block of dopamine cell firing in response to haloperidol administration in this model. PMID- 1422839 TI - Changes in D2 but not D1 receptor binding in the striatum following a selective lesion of striatopallidal neurons. AB - We have used the immunotoxin OX7/saporin, a suicide transport agent, to selectively lesion striatopallidal neurons. Following injection of OX7/saporin into the globus pallidus, in situ hybridization for preproenkephalin mRNA was examined in the striatum to confirm successful retrograde neurotoxicity. Comparison of D1 and D2 receptor binding in the striatum demonstrated that D2 but not D1 receptor binding sites are localized to striatopallidal neurons. PMID- 1422840 TI - Amelioration of ischemic spinal cord damage by postischemic treatment with propentofylline (HWA 285). AB - The effect of the xanthine derivative propentofylline (HWA 285) on metabolic and functional recovery in rabbit spinal cord after 20 and 30 min ischemia and 4 days of reperfusion was investigated. Pre-treatment with 20 mg/kg significantly improved recovery of the energy state in the spinal cord, however, without significant functional recovery of hindlimbs. In contrary, post-treatment with HWA 285 recovered the energy state to pre-ischemic value and also significantly improved functional recovery. These findings suggest that the neuroprotective mechanism of HWA 285 in the spinal cord is not associated with inhibition of glutamate release as supposed to operate in the gerbil brain. PMID- 1422841 TI - Optic nerve transection decreases 2-[125I]iodomelatonin binding in the chick optic tectum. AB - The distribution of specific 2-[125I]iodomelatonin binding sites in the various layers of the chick optic tectum was analyzed using quantitative receptor autoradiography. Following unilateral optic nerve transection, binding in the optic fiber layer and superficial retinorecipient layers of the contralateral tectum was significantly decreased at 7 and 14 days, but not at 1 day, following transection. The results are consistent with the presence of presynaptic melatonin receptors on axon terminals of retinotectal fibers. PMID- 1422842 TI - Preservation of energy metabolites by carnitine in the mouse brain under ischemia. AB - Ischemia (decapitation) caused marked changes of energy metabolites in the mouse brain. However, the changes were clearly less severe, when the mouse was pre treated with L-carnitine. This suggests that L-carnitine may protect the brain from the ischemic attack. Since D-carnitine showed a similar effect, the effects may be due to mechanism(s) other than the 'classical' function of carnitine. PMID- 1422843 TI - Pre-Botzinger complex in cats: respiratory neuronal discharge patterns. AB - Patterns of respiratory neuronal discharge in the pre-Botzinger complex, hypothesized as a brainstem site generating respiratory rhythm, are described in adult cats. Signals were recorded from neurons in the Botzinger complex, pre Botzinger complex and rostral ventral respiratory group (rVRG) of anesthetized adult cats. The pre-Botzinger complex, located caudal to expiratory-modulated Botzinger neurons, contained a mix of neurons with inspiratory-modulated, expiratory-modulated, or phase-spanning patterns of impulse activity, in contrast to the more homogenous neuronal distributions characteristic of adjacent Botzinger and rVRG regions. PMID- 1422844 TI - Comparison of the effects of NMDA antagonists on medial vestibular nucleus neurons in brainstem slices from labyrinthine-intact and chronically labyrinthectomized guinea pigs. AB - The responses of ipsilateral medial vestibular nucleus (MVN) neurons in brainstem slices from guinea pigs compensated for a unilateral labyrinthectomy (UL), to the N-methyl-D-asparate (NMDA) receptor/channel antagonists CPP and MK801, were compared with those of MVN neurons in brainstem slices from labyrinthine-intact guinea pigs observed in a previous study. The average resting activity of ipsilateral MVN neurons from compensated animals was significantly higher than that for MVN neurons from labyrinthine-intact animals; however, there were no significant differences in the average magnitude of the decrease in firing rate from baseline in response to CPP or MK801 and the only significant difference in the number of responses was to MK801, where fewer ipsilateral MVN neurons from compensated animals responded with a decrease in firing rate. These results suggest that vestibular compensation is not associated with an up-regulation or increased affinity of NMDA receptors in the MVN ipsilateral to the UL. PMID- 1422845 TI - Selective activation of mesoamygdaloid dopamine neurons by conditioned stress: attenuation by diazepam. AB - Populations of dopamine (DA) neurons in the rat brain are selectively activated by stress, and the response is attenuated by the administration of anxiolytics. Given the role of the component nuclei of the amygdaloid complex in conditioned associations, stress responses and the anxiolytic effects of benzodiazepines, we hypothesized that particular mesoamygdaloid DA projections might be especially sensitive to the effects of conditioned stress and to diazepam (DZ). We mapped the effect of a conditioned stressor on the concentration of the DA metabolite homovanillic acid (HVA) in distinct amygdaloid nuclei and other brain nuclei and areas and the effect of DZ (1 or 3 mg/kg) on the conditioned response in drug experienced subjects. The conditioned stress paradigm resulted in significant elevations in classical indices of stress, including serum corticosterone and plasma epinephrine. Conditioned stress-induced increases in the estimated activity of DA neurons were specific for DA neurons projecting to the central, basolateral and lateral amygdaloid nuclei, and for DA projections to the dorsal septal nucleus. Conditioned stress-induced increases in the HVA concentration of responsive amygdaloid nuclei were antagonized by low, anxiolytic doses of DZ. These results indicate a role for a subset of mesoamygdaloid DA projections in transducing the impact of perceived stressors on the output of the amygdaloid complex. A role for particular amygdaloid DA projections in the formation of conditioned fear or anticipatory anxiety and its modulation by anxiolytics is also suggested. PMID- 1422846 TI - Protective effects of serotonin reuptake inhibitors, citalopram and clomipramine, against hippocampal CA1 neuronal damage following transient ischemia in the gerbil. AB - To clarify the role of serotonin in cerebral ischemia, we examined the effects of selective serotonin reuptake inhibitors, citalopram and clomipramine, on ischemic neuronal damage in the gerbil. Pretreatment with citalopram (40 mg/kg i.p.) and clomipramine (20 mg/kg i.p.) protected against neuronal destruction of hippocampal CA1 pyramidal cells following 5 min of forebrain ischemia. Furthermore, microdialysis assays showed that a striking increase in extracellular excitatory amino acid levels during ischemia was significantly inhibited by pretreatment with citalopram and clomipramine. However, citalopram (40 mg/kg i.p.) did not alter the extracellular amino acid concentrations in normal gerbils. Thus, serotonin reuptake inhibitors have a protective effect against ischemic neuronal damage. Furthermore, the present result suggests that the protective effect is mediated through prevention of the accumulation of extracellular excitatory amino acids during and after ischemia. PMID- 1422847 TI - Immunocytochemical localization of 205 kDa microtubule-associated protein (205 kDa MAP) in the guinea pig organ of Corti. AB - We have studied the immunocytochemical localization of microtubule-associated proteins (MAPs) in the guinea pig organ of Corti. Using immunological methods with antibodies against MAP1A, MAP1B, MAP2, tau and 205 kDa MAP, we have identified 205 kDa MAP as a major MAP of the sensory epithelium in the organ of Corti. Immunoperoxidase microscopic study has shown that both cochlear hair cells and supporting cells reacted with anti-205 kDa MAP antibody. Immunoelectron microscopy revealed that 205 kDa MAP was associated with most microtubules in the sensory epithelial cells. It was also associated with the microtubules of bundle structures within supporting cells, suggesting that this MAP might form a part of cross-bridges between microtubules and between microtubules and actin filaments in the bundle structure. In contrast, MAP1A, MAP1B and tau, which are known to be expressed in neuronal tissue, were localized only in nerve fibers in the organ of Corti, not in the sensory epithelium. MAP2, which is known to be localized in dendrites and soma of nerve cells, was not distributed in nerve fibers in the organ of Corti. These results suggest possible roles of the 205 kDa MAP in the formation and maintenance of the highly polarized morphology of the epithelial cells of the organ of Corti, through stabilization and modulation of microtubule networks of these cells. PMID- 1422848 TI - Changes of labile metabolites during anoxia in moderately hypo- and hyperthermic rats: correlation to membrane fluxes of K+. AB - The objective of this study was to assess the influence of temperature on the coupling among energy failure, depolarization, and ionic fluxes during anoxia. To that end, we induced anoxia by cardiac arrest in anesthetized rats maintained at a body temperature of either 34 degrees C or 40 degrees C, measured extracellular K+ concentration (K+e), and froze the neocortex through the exposed dura for measurements of phosphocreatine (PCr), creatine (Cr), ATP, ADP, and AMP, glucose, glycogen, pyruvate and lactate content after ischemic intervals of maximally 130 s. Free ADP (ADPf) concentrations were derived from the creatine kinase equilibrium. Hypothermia reduced the initial rate of rise in K+e, and delayed the terminal depolarization; however, both hypo- and hyperthermic animals showed massive loss of ion homeostasis at a K+e of 10-15 mM. The initial rate of rise in K+e did not correlate to changes in ATP, or ATP/ADPf ratio, suggesting that temperature changes per se may control the degree of activation of K+ conductances. The results clearly showed that, in both hyper- and hypothermic subjects, energy failure preceded the sudden activation of membrane conductances for ions. The results indicate that temperature primarily influences membrane permeability to ions like K+e (and Na+), and that cerebral energy state is secondarily affected. It is proposed that the higher rate of rise of K+e at high temperatures accelerates ATP hydrolysis primarily by enhancing metabolic rate in glial cells. PMID- 1422849 TI - Localization of the central antinociceptive effects of diclofenac in the rat. AB - The ethacrynic acid-induced writhing response (WR) in the rat was studied after microinjections of diclofenac 0.1 ng-1 microgram/0.5 microliter (0.32 pmol to 3.2 nmol) into several brain regions involved in control of nociceptive behavior. The WR was inhibited after injections into the periaqueductal grey matter (PAG), ventromedial thalamus (VM), medial preoptic area (MPA) and the nucleus raphe magnus (NRM). Morphine 50 ng/0.5 microliter (0.16 nmol) was used as a positive control and vehicle injections were performed as negative reference. After diclofenac, there was a dose-dependent reduction of the WR with a threshold dose of approximately 1-10 ng in all brain areas studied except the nucleus reticularis paragigantocellularis interna (NRPGi). Naloxone 50 ng/0.5 microliter (0.15 nmol) administered into the same site 30 min after diclofenac injection, antagonized the diclofenac-induced inhibition of the WR almost completely in PAG and VM. Previous results demonstrate a central, naloxone-reversible component in the analgetic action of diclofenac. A qualitatively similar, centrally induced inhibition of the WR may be elicited after injections into PAG, VM and NRM. Thus, in addition to its peripheral mechanism of action, the non-steroidal anti inflammatory drug, diclofenac, has a central mechanism of action which directly or indirectly involves a central opioid component. PMID- 1422850 TI - Clorazepate synchronizes cultured rat C6 glioma in the early G1 phase of the cell cycle. AB - A water soluble benzodiazepine, clorazepate, has been used to establish the point of benzodiazepine proliferative arrest in the rat C6 glioma. Clorazepate inhibited C6 proliferation in a dose-dependent manner with an IC50 value of 280 microM, as judged by a nuclei counting procedure. Release of cells from a 48 h exposure to 350 microM clorazepate, at which over 70% of the cells were arrested, resulted in a synchronous entry into S phase 8-9 h later, as evidenced by a sharp increase in the incorporation of [3H]thymidine. This restriction point was demonstrated to be 2-3 h into the G1 phase by measuring the length of G1 in synchronized populations of C6 cells obtained by selection of mitotic figures from an asynchronous culture. Synchronous arrest of C6 by clorazepate required an exposure period of 24-36 h, approximately twice the doubling time of the cell line. A morphological study confirmed an early G1 point of proliferative arrest. Clorazepate synchronized cells exhibited a uniform morphology with the majority of cells assuming a configuration representative of anchorage-dependent cells in an early phase of attachment. The majority of cells were somewhat rounded and attached to the substratum by cytoplasmic 'skirts' with punctate structures which may represent focal adhesion points. PMID- 1422851 TI - Neuropeptides and monoamines in the torus semicircularis of the carp (Cyprinus carpio). AB - The distribution of vasoactive intestinal polypeptide, gastrin-releasing peptide, gamma-melanocyte-stimulating hormone, alpha-neo-endorphin, angiotensin II, cholecystokinin-8, serotonin, and tyrosine hydroxylase has been studied in the nuclei lateralis and centralis of the Cyprinus carpio torus semicircularis using an indirect immunoperoxidase technique. In both nuclei, we found vasoactive intestinal polypeptide, gastrin-releasing peptide, gamma-melanocyte-stimulating hormone, alpha-neo-endorphin, serotonin, and tyrosine hydroxylase immunoreactive fibers, whereas the torus semicircularis was not immunoreactive for cholecystokinin-8 and angiotensin II. Moreover, no immunoreactive cell bodies containing peptides or monoamines were observed. The presence of these peptides and monoamines in both the nuclei lateralis and centralis suggests that such substances might be involved in the control of the visual, auditive, and/or lateral line information systems. PMID- 1422852 TI - Binocularity and excitability loss in visual cortex cells of corpus callosum transected kittens and cats. AB - The contribution of the corpus callosum to binocularity of visual cortex cells and to their responsiveness was studied in cats. Electrophysiological recordings of the responses of single cells to visual stimulation was performed in the callosal projection zone, visual cortex area 17-18 boundary in callosotomized cats. Callosotomy was carried out by transection of the visual segment of the corpus callosum in 6-7-week-old kittens and in acute and chronic adult cats (postoperative recovery time: 11 days-39 months). While in our normal cats the common proportion of binocularly driven cells (79.8%) was found (66.3% in the sham controls), a remarkable diminution (29.7%) was found in the callosotomized kittens, in the acute (39.7%) and in the chronic (50.6%)-operated cats. We have also found a change in the amount of binocularity as function of postoperative recovery time. While the proportion of binocular cells was conceivable (60.7%) in the short- and intermediate-term callosotomized cats (postoperative time: 0.3-5.5 months), it was diminished (36.9%) in the long-term (6.5-39 months) chronic cats. As to the responsiveness level, it was found that visual responsive cells constituted 88% of the cells in the normal and 80.3% in the sham controls. In comparison, they constituted 69.2% in the acute, 54.4% in the chronic and 52.8% in the callosotomized kittens. Furthermore, callosal transection had produced a symmetric effect in the two hemispheres, regarding binocularity and responsiveness. It has been thus concluded that the corpus callosum is essential for the mediation of binocular functions between the two hemispheres; in addition, cortical excitability has been also found to depend on callosal integrity. PMID- 1422853 TI - Protein kinase C activators stimulate beta-endorphin secretion from hypothalamic cells. AB - Relatively little is known about the regulation of secretion of hypothalamic beta endorphin, the potent opioid that is believed to play a variety of physiological roles in brain. Previous work has shown that arginine vasopressin (AVP), which acts in brain primarily via activation of the phosphoinositol (PI) second messenger system, stimulates secretion of hypothalamic beta-endorphin. To test the hypothesis that activators of protein kinase C (PKC), which is activated following PI hydrolysis, stimulates secretion of beta-endorphins from hypothalamus, we studied the separate effects of stimulators of PKC including phorbol ester 12-myristate-13-acetate (PMA) and 1-oleolyl-2-acetyl glycerol (OAG- a diacyl glycerol analogue) on secretion of immunoreactive (IR-) beta-endorphin (measured by RIA) from dissociated fetal rat hypothalamic cell cultures. We also studied AVP and angiotensin II (Ang II), hypothalamic peptides which activate the PI second messenger pathway, and interactions of PMA and forskolin (FSK), an activator of the cyclic AMP/protein kinase A (PKA) pathway. PMA, OAG, AVP, and Ang II stimulated IR-beta-endorphin secretion. The stimulatory effect of both PMA and FSK on IR-beta-endorphin secretion was greater than that of PMA or FSK alone and was essentially additive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422854 TI - Tyrosine pretreatment alleviates suppression of schedule-controlled responding produced by corticotropin releasing factor (CRF) in rats. AB - Disruption of performance observed when animals are exposed to physical stressors which deplete brain catecholamines can be alleviated by pretreatment with the catecholamine precursor tyrosine. Central administration of the stress hormone corticotropin releasing factor (CRF) has been shown to affect a variety of behaviors and also to potently increase the release of central catecholamines. Since CRF-induced disruption of behavior may involve CRF-induced depletion of brain catecholamines, the present study examined whether tyrosine would alleviate suppression of schedule-controlled responding in rats resulting from ICV administration of CRF. Administration of CRF (1.0 microgram-10 micrograms) produced dose-dependent suppression of response rate and total number of earned reinforcers in rats responding on a multiple fixed-interval 60 s/fixed-ratio 20 schedule for food reinforcement. Pretreatment with 200 mg/kg tyrosine (IP) administered with ICV saline decreased response rate but did not lower total reinforcers, whereas 400 mg/kg of tyrosine decreased both. Injection of 400 mg/kg tyrosine reduced, but did not completely restore, CRF-induced suppression of behavior. The 200 mg/kg tyrosine dose was less effective in alleviating CRF induced suppression of performance. These data indicate that pretreatment with the catecholamine precursor tyrosine can partially ameliorate performance decrements resulting from CRF administration. PMID- 1422855 TI - Inhibitory inputs to the subfornical organ from the AV3V: involvement of GABA. AB - Action potentials were recorded extracellularly from single neurons in the subfornical organ (SFO) of the pentobarbital-anesthetized cat following stimulation of the regions surrounding the anteroventral third ventricle (AV3V). Of 328 SFO neurons studied, 103 were antidromically activated, showing direct projections from the SFO to the AV3V. However, the major effects of stimulations of the AV3V on SFO neurons were orthodromic inhibition; almost 30% of SFO neurons were inhibited by various sites in the AV3V, while a smaller proportion of cells were excited. Local application of bicuculline, an antagonist for GABA, attenuated the inhibitory responses induced by stimulation of the AV3V in seven out of eight neurons tested. Application of GABA inhibited 16 out of 24 neurons, while that of bicuculline alone excited 11 out of 26 neurons, suggesting the tonic inhibitory action of GABA on some SFO neurons. On the other hand, application of kynurenic acid, a nonspecific antagonist for the excitatory amino acids, did not affect the excitatory responses induced by stimulation of the AV3V, but kynurenic acid itself inhibited 6 out of 18 neurons tested. Application of glutamate excited most SFO neurons. This suggests that the excitatory amino acids may be the transmitter(s) of interneurons in the SFO but may not mediate the excitation from the AV3V. PMID- 1422856 TI - Induction of c-fos immunostaining in the rat brain after the systemic administration of nicotine. AB - To search for evidence of altered neuronal gene expression in response to exposure to the highly addictive drug nicotine, rat brains were examined by immunocytochemistry for the fos protein after the systemic administration of nicotine. The drug was administered as an IV infusion over 1 h At a dose of 2 mg/kg, the most dramatic nicotine-induced fos nuclear immunostaining was seen in central visual pathways, including the superficial superior colliculus and the medial terminal nu. of the accessory optic tract, in the interpeduncular nu. Notably, many regions with high levels of nicotine binding sites, including the medial habenula, thalamus, substantia nigra, and ventral tegmental area, failed to express the c-fos gene with this schedule of nicotine administration. A minimal increase in fos immunostaining was seen after a nicotine dose of 0.5 mg/kg, with a much greater response after 1 or 2 mg/kg. The response was seen as soon as 60 min after the beginning of the infusion, was maximal at 2-3 h, and declined thereafter. c-fos expression was substantially attenuated in the superficial gray layer of superior colliculus, medial terminal nucleus of the accessory optic tract, and the interpeduncular nucleus by pretreatment with the centrally acting nicotine antagonist mecamylamine, 5 mg/kg IP, but not with the peripherally acting antagonist hexamethonium, 4 mg/kg IP. These observations identify a subset of central nervous system neurons that respond to nicotine with altered expression of the immediate early gene c-fos. These neurons presumably undergo long-term changes in gene expression as a result of acute exposure to high doses of nicotine. PMID- 1422857 TI - Ethanol alters monoamines in specific mouse brain regions. AB - Ethanol (3.5 g/kg 60 min post-IP injection) produced the following changes in regional brain monoamine levels and in the respective metabolite/neurotransmitter ratios: for the noradrenergic system, MHPG was decreased in the amygdala and increased in the hypothalamus, while the MHPG/NE ratio was increased in the prefrontal cortex and the hypothalamus. For the dopaminergic system, DA was decreased in the olfactory tubercle, DOPAC was increased in the prefrontal cortex and septum, and DOPAC/DA was increased in the prefrontal cortex, septum, striatum, and hypothalamus. HVA was increased in the prefrontal cortex and septum, while HVA/DA was increased in the same regions plus the olfactory bulb. 3MT was decreased in the olfactory tubercle and striatum. The serotonergic system was not altered. The results demonstrate that ETOH produces selective regional changes in the concentration and utilization of monoamines in mouse brain with a predominant influence on dopaminergic systems and a lesser effect on noradrenergic activity. PMID- 1422859 TI - Descending pain inhibitory system involved in acupuncture analgesia. AB - The descending pain inhibitory system (DPIS) associated with acupuncture analgesia (AA), caused by low frequency stimulation of an acupuncture point, was identified by the results of lesion and stimulation procedures previously determined to differentiate the afferent and efferent paths in rats. The DPIS starts in the posterior arcuate nucleus and descends to the hypothalamic ventromedian nucleus (HVM) from whence it divides into two pathways: one path, the serotonin mediated path, descends through the ventral periaqueductal central gray (V-PAG) and then to the raphe magnus (RM). The other, the noradrenaline mediated path, descends through the reticuloparagigantocellular nucleus (NRPG) and part of the reticulogigantocellular nucleus (NRGC). The afferent and efferent paths are both present in the RM and NRGC, and were separately identified by means of the analgesia (SPA) produced by stimulation of the separate regions in AA responders and nonresponders, because SPA of these regions in nonresponders produced only efferent pathway mediated analgesia. PMID- 1422858 TI - Eight-arm maze performance, neophobia, and hippocampal cholinergic alterations after prenatal oxazepam in mice. AB - Outbred CD-1 mice were exposed to oxazepam (15 mg/kg PO twice/day) on days 12-16 of fetal life, i.e., at a critical ontogenetic stage of Type II benzodiazepine (BDZ) receptor increase, and fostered at birth to untreated dams. At adulthood, radial arm maze performance, activity-habituation test in an open-field arena (either single 15-min test or three 5-min sessions at 24-h intervals), approach to a novel stimulus object, and amphetamine or scopolamine effects thereon were assessed in male progeny. Overall, the oxazepam exposed (OX) mice were much less efficient in the radial arm maze task than the vehicle exposed (VEH) animals. Pre test scopolamine injection, but not amphetamine, significantly impaired the arm maze performance of OX mice when compared with the corresponding VEH-scopolamine animals. In separate nonlearned behavioral tasks, prenatal oxazepam did not affect either baseline activity levels in the open field or the response to the amphetamine and the scopolamine challenge, while it considerably increased the latency of first approach to a novel object and produced a deficit of habituation in the course of the subsequent exploratory period. Concomitant investigation at the neurochemical level showed that the adult OX animals had a significant increase in both Bmax and in the affinity (Kd) of cholinergic muscarinic receptors in the hippocampal formation when compared to the vehicle-exposed controls. PMID- 1422860 TI - Fate of septohippocampal neurons following intracerebroventricular injections of colchicine. AB - Injection of colchicine into the lateral ventricles (ICV) of rats results in a selective loss of neurons immunoreactive for choline acetyltransferase (ChAT) in the medial septum (MS) and a concomitant loss of acetylcholinesterase (AChE) positive fibers in the hippocampus. To determine if this loss of cholinergic cells is due to neuronal death, septohippocampal neurons were retrogradely labeled with fluoro-gold (FG) 1 week prior to the injection of colchicine. Numbers and sizes of FG-labeled and ChAT-immunoreactive neurons were assessed 3, 6, and 10 weeks after ICV colchicine. In line with previous observations, numbers of ChAT-immunoreactive cells were reduced to fewer than 50% of control in the MS and to fewer than 60% of control in the vertical limb of the diagonal band (vDB). Three weeks after ICV colchicine, numbers of FG-labeled neurons were reduced to 48% in the MS and 24% in the vDB. By 6 weeks, the number in the MS decreased further to 31% of control, whereas the number remained at 24% in the vDB. Ten weeks after colchicine, the numbers of retrogradely labeled cells in both the MS and vDB had decreased to 11% of control. The cells which remained were not reduced in cross-sectional area or in diameter. These data suggest that the selective loss of cholinergic neurons in the MS which occurs following ICV colchicine is due to neuronal death and not just loss of ChAT expression. PMID- 1422861 TI - Effects of medial septal lesions on an operant delayed go/no-go discrimination in rats. AB - Male hooded rats received either a medial septal lesion or a control operation. The rats were then tested on an operant go/no-go discrimination task, first without a delay contingency (20 days), followed by 25 days under an 8-s delay. A discrete trial procedure with symmetrical reinforcement was used. Each trial began with the operant chamber darkened, except for back illumination of a centrally located press panel. Depression of this panel extinguished the back light and initiated a random presentation of either the go stimulus (2800 Hz tone) or the no-go stimulus (10 Hz pulsing light) for 3 s. Stimulus termination initiated the appropriate delay contingency (0 s or 8 s), which was followed by the cued availability of a lever for 2 s. If the rat pressed the lever on go trials, or refrained from pressing the lever on no-go trials, a food pellet was delivered. The data (% correct responses) were averaged over 5-day blocks. Overall, the septal-lesioned rats performed significantly better than the control rats under both O-s delay (p < 0.025) and 8-s delay (p < 0.001) contingencies. Although there was not a significant difference between the groups during the last block of the O-s delay (septals 93% correct, controls 89% correct, p > 0.05) or the first block of the 8-s delay (septals 54% correct, controls 53% correct, p > 0.05), the septal-lesioned animals performed significantly better than the controls during all the remaining phases of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422862 TI - Effects of hyperthermia on the effectiveness of MK-801 treatment in the gerbil hippocampus following transient forebrain ischemia. AB - The effects of dizocilipine maleate (MK-801), a noncompetitive N-methyl-D aspartate (NMDA) receptor/channel antagonist, were tested on the dysfunction of neurotransmitter and signal transduction systems and morphological damage 7 days after transient forebrain ischemia in gerbils. Neurotransmitter system (adenosine A1, muscarinic cholinergic receptor) and signal transduction system (inositol 1,4,5-trisphosphate receptor: IP3, protein kinase C: PKC, L-type calcium channels) binding sites were mapped by in vitro quantitative receptor autoradiography. All ligands used in the present study decreased significantly in the CA1 subfield 7 days after ischemia. In normothermic animals, pretreatment with MK-801 failed to protect against decreased receptor binding in the hippocampus 7 days after ischemia. Moreover, in a morphological study, pre- and posttreatment of MK-801 failed to show protective effects against ischemic neuronal damage. On the other hand, pretreatment of MK-801, without maintaining body temperature, prevented the neuronal death of CA1 subfield 7 days after ischemia. These results weaken the hypothesis that NMDA receptor/channel may play a pivotal role in the pathogenesis of neuronal damage after transient forebrain ischemia. PMID- 1422863 TI - A detergent-solubilized nicotinic acetylcholine receptor of Caenorhabditis elegans. AB - We have used a spin column assay to study the detergent-solubilized levamisole receptor, a nicotinic acetylcholine receptor of the nematode Caenorhabditis elegans. The receptor can be successfully solubilized in detergent solutions of Triton X-100, Lubrol PX, or sodium cholate. Centrifugal gel filtration assay using the tritiated ligand [3H]meta-aminolevamisole ([3H]MAL) provides a greater signal and a better signal-to-noise ratio for soluble levamisole receptor binding than either polyethylene glycol precipitation or DEAE filter assay with the same ligand. As for membrane-bound receptor, the detergent-solubilized levamisole receptor consists of more than one affinity state. Detergent solubilization appears to increase the affinity of all states for [3H]MAL (Kd for the highest affinity solubilized [3H]MAL binding state, 41 +/- 5 pM). Data is presented on the equilibrium binding and the association and dissociation reaction rates of the receptor. The similar relative efficacy with which various compounds inhibit specific [3H]MAL binding and deficiencies in solubilizable high affinity specific [3H]MAL binding in two receptor mutants show that the solubilized receptor is the same nicotinic acetylcholine receptor that is detected by assaying membrane-bound specific [3H]MAL binding. The detergent-solubilized levamisole receptor is stable at 0 degree to 4 degrees C, making receptor purification feasible. PMID- 1422865 TI - Distribution of corticotropin-releasing hormone immunoreactivity in golden hamster brain. AB - The distribution of corticotropin-releasing hormone-immunoreactive (CRH-IR) neurons and fibers was observed in golden hamsters. CRH-IR neurons and fibers were observed within the hypothalamus, thalamus, amygdala, cortex, midbrain, and hindbrain. The largest numbers of CRH-IR neurons were seen within the magno- and parvocellular divisions of the paraventricular nucleus of the hypothalamus and within the septum, bed nucleus of the stria terminalis, preoptic area continuum. The highest density of immunoreactive fibers was observed in the external zone of the median eminence. In addition, many immunoreactive fibers were observed within the bed nucleus of the stria terminalis and the preoptic area. The distribution obtained in hamsters was compared with previously reported distributions from rats, and both were generally similar. PMID- 1422864 TI - Evidence for opiate-dopamine cross-sensitization in nucleus accumbens: studies of conditioned reward. AB - We investigated opiate-amphetamine interactions within the nucleus accumbens in responding for conditioned reward. Separate groups of animals received 4-day intra-accumbens treatment with either saline, morphine (0.5 microgram/0.5 microliter), [D-Ala2 NMe-Phe4 Gly-ol5]-Enkephalin (DAMGO; 1.0 micrograms/0.5 microliter), or [D-Pen2,5]-Enkephalin (DPEN; 2.0 micrograms/0.5 microliter). One two subsequent test days, these rats were given a challenge of d-amphetamine (2.0 and 10.0 micrograms/0.5 microliter) and responding for conditioned reward was measured. In the conditioned reinforcement (CR) procedure, food-deprived animals were trained in an initial phase to associate a food reward (primary reinforcement) with a compound stimulus (light/click). In the next phase, a lever was introduced and responding on the lever produced the compound stimulus alone (secondary reinforcement). Previous evidence shows that psychostimulants but not opiates markedly potentiate responding for conditioned reward. In the present design, animals previously treated with either morphine or DAMGO (preferential mu agonists) showed potentiated lever responding following amphetamine challenges, relative to either DPEN- or saline-treated animals. These findings show that prior exposure of nucleus accumbens neurons to mu-selective opiates induces sensitization to the effects of amphetamine. The results are discussed in terms of opioid effects on dopamine transmission and second messenger systems. PMID- 1422866 TI - Hippocampal neuronal damage after transient forebrain ischemia in monkeys. AB - To investigate cerebral injury in the monkey due to transient ischemia, monkeys were each subjected to temporary occlusion of eight (bilateral common carotid, internal and external carotid, and vertebral) major arteries. After 0 (control), 5, 10, 13, 15, and 18 min occlusion, blood flow was restored. The monkeys were sacrificed by perfusion fixation 5 days after the operation, and all brain regions were then histologically examined for ischemic neuronal changes induced by the occlusion. The amplitude of EEG signals from skull and scalp became almost isoelectric within 1-6 min after the onset of occlusion. The EEG signals from the hippocampus were markedly attenuated within 1-4 min, although they did not become completely isoelectric. Blood pressure was significantly increased after 10-min ischemia. Five-min occlusion produced no ischemic neuronal changes except a slight increment of glial cells in the striatum and III, V, and VI layers of the neocortices. After 10- to 15-min occlusion, there were ischemic cell changes restricted exclusively to the CA1 subfield of the hippocampus. Eighteen-min occlusion produced more prominent ischemic neuronal damage in the CA1 subfield of the hippocampus, but ischemic neuronal damage was no longer confined to the hippocampus. These results suggest that only the CA1 subfield of the monkey hippocampus could be damaged by mild ischemic insult. We demonstrate that the limited lesion of the hippocampus, especially the CA1 subfield, after 10- to 15 min occlusion of eight arteries in the monkey, produces a model equivalent to human amnesia caused by transient ischemic insult. PMID- 1422867 TI - Vitamin E attenuates the toxic effects of 6-hydroxydopamine on free radical scavenging systems in rat brain. AB - Rats were divided into the following four groups namely (a) sham-operated control, (b) 6-OHDA-treated, (c) sham-operated vitamin E-fed and (d) Vitamin E fed treated with 6-OHDA. Total glutathione (GSH) and superoxide dismutase (SOD) were measured in brainstem (BS), striatum (ST), hippocampus, frontal cortex, and nucleus accumbens (N. Acc.). GSH and SOD levels were significantly decreased in all regions of 6-OHDA-treated rats compared to controls. Feeding of vitamin E resulted in a significant reduction of GSH in ST and N. Acc. but caused increases in SOD in BS, ST, and N. Acc. Pretreatment of rats with vitamin E caused significant attenuation of the effects of 6-OHDA on GSH and SOD in most of the brain regions. These results show that vitamin E can spare the scavenging systems from the injurious effects of 6-OHDA. PMID- 1422868 TI - [Contribution of a hematologic cytogenetic laboratory to the diagnosis, classification and prognosis of various hematologic malignancies]. AB - The presence of an haematological cytogenetic laboratory into a clinical unit allowed to realize a close collaboration between clinicians and cytogeneticists, and to achieve a maximal exploitation of the results of the bone marrow cytogenetic studies in some haematological malignancies. It made it possible to perform sequential bone marrow karyotypes studies during the different phases of a disease: We could thus establish: The diagnostic value of cytogenetic findings for chronic myelocytic leukaemia, secondary acute leukaemia, but not for dysglobulinemias. The prognostic value of cytogenetic abnormalities in chronic myelocytic leukaemia where additional abnormalities to the Ph1 are a hallmark of blastic transformation; in primitive dysmyelopoiesis where they represent a bad prognostic factor; in dysglobulinemias, where they are a signal of terminal evolution. In all these diseases, only complex and multiple abnormalities have a prognostic significance pointing out the emergence of a malignant clone, where as rare and single abnormalities are of no significance. Nowadays, haematological cytogenetic must be bound to molecular biology. PMID- 1422869 TI - [Eulogy of Jean-Louis Parrot (1908-1991)]. PMID- 1422870 TI - [Iatrogenic disease observed in a hospital setting. II. Analysis of causes and suggestions for novel preventive measures]. AB - In a previous article, we reported the results of a survey of iatrogenic illness in teaching hospitals. In the second part of this study, we shall consider the origins of the 109 adverse events which occurred in a 24-hour period among 1733 hospital patients in a total of 43 units (mean prevalence, 6.28%). In a total of 89 cases (83 of which were drug-related and 6 of which were of various non instrumental causes), self-treatment and/or poor patient compliance appeared to be the main cause in 16 (18%); negligence or erroneous prescription (non-respect of a contraindication, wrong indication or dosage, excessive duration of treatment, inadequate monitoring, etc...) appeared to be responsible in 27 cases (30.3%). It may be that at least some of these cases of iatrogenic illness due to errors or negligence on the part of the patient and/or physician (48.3%) could be avoided in future by better training of health personnel and improved public health education. The human and financial costs of iatrogenic illness show that risk-prevention measures are required; we propose a number of strategies concerning both initial training in medical school and ongoing education in therapeutics, together with ways of improving the behaviour of both physicians and the pharmaceutical industry. The latter suggestions are addressed at the media and the health authorities; some concern legislation, while others are aimed at improving early public health education, an essential element in this setting. PMID- 1422871 TI - [Bronchial epithelium and asthma]. AB - Asthma is a type of chronic desquamative bronchitis and, so far, the role of the bronchial epithelium in this disease has not been fully assessed. There are at least 3 ways by which bronchial epithelial cells may modulate the pathophysiology of asthma: 1. They are resident cells, capable of liberating pro-inflammatory mediators, which may be chemotactic for other cells such as neutrophils and eosinophils. 2. An asthmatic attack results in desquamation of the bronchial epithelium which may have multiple consequences. 3. A repair phase must follow the desquamation although the precise mechanisms underlying this phase are incompletely understood. The level of reparation is likely to play an important role in the prognosis of the disease. PMID- 1422872 TI - [Importance of hypergastrinemia in diagnosis of Biermer's disease in adults]. AB - Achlorhydria that is due to antrum sparing atrophic gastritis is a characteristic finding in pernicious anemia. As a consequence of this achlorhydria serum gastrin level rise. Usually several signs are required for assessing a pernicious anemia: megaloblastic anemia, low serum cobalamin level, positivity of a Schilling test, low level of intrinsic factor in the gastric juice, existence of anti-intrinsic factor antibodies in plasma and/or in gastric juice. In this study the usefulness of the serum gastrin level is assessed. We report here the results in investigating sixteen patients with a pernicious anemia. All had: megaloblastic changes on bone marrow examination, serum cobalamin level lower than 150 pg/ml. For 14 patients the performed Schilling test was positive. For 2, no Schilling test was done, but anti-intrinsic factor antibodies were elevated. Serum gastrin levels were higher than 250 pg/ml (254 to 1770 pg/ml). In our patients with pernicious anemia, as a result of hypo or achlorhydria, serum gastrin increase was higher than in any other cause of hypochlohydria: anti-acid treatment, vagotomy... Measurement of serum gastrin is easy. High levels are simple to explain if found together with a sparing antrum atrophic gastritis and/or a low level of serum cobalamin. Serum gastrin measurement may be a cornerstone to rapid and reliable diagnosis of pernicious anemia. PMID- 1422873 TI - [Application of multifactorial statistical calculation searching for a correlation between fat soluble vitamins and cancer]. AB - The aim of this work was to combine computer methodology applied to multi factorial statistical calculations with liquid chromatography results on the analyses of serum levels of retinol, beta-carotene and tocopherols in healthy subjects and in patients with various cancers associated with certain tumor markers. Our results show that the serum levels of the vitamins studied differed in cancer patients in comparison to healthy controls. These results also confirm published data showing that serum variations are generally not characteristic of a specific tumor localization, without indicating if these variations are a cause or an effect of tumor development. Computerized multifactorial analysis taking into account the levels of all vitamins and tumor markers chosen, however, enabled us to classify the different tumors in five groups: cancers of the nervous system, urogenital tract cancers, laryngo-pulmonary cancers and two groups of digestive system cancers. This new approach may lead to the constitution of a data bank on the localization of tumors, as well as a reference system for all analyses of serum levels of vitamins associated with tumor markers. PMID- 1422874 TI - [Demand for classification of the climate in the town of Blotzheim (Upper Rhine)]. PMID- 1422875 TI - DIROM: an experimental design interactive system for directed mutagenesis and nucleic acids engineering. AB - A computer system DIROM for oligonucleotide-directed mutagenesis and artificial gene design has been designed for better experimental planning and control. DIROM permits searching for optimal oligonucleotides with respect to certain important parameters, namely sufficient energy of oligonucleotide-target hybridization, the secondary structure of oligonucleotide and target DNA, the presence of alternate binding sites in the target DNA and terminal G/C pairs. It can also be used to plan polymerase chain reaction experiments, for optimal primer selection, in sequencing, etc. DIROM enables one to search for both existing and potential restriction sites, to perform vector + target sequence construction. The system consists of a set of original algorithms that formalize the empirical knowledge of oligonucleotide action as primers. PMID- 1422876 TI - First and second moment of counts of words in random texts generated by Markov chains. AB - An exact expression for the variance of random frequency that a given word has in text generated by a Markov chain is presented. The result is applied to periodic Markov chains, which describe the protein-coding DNA sequences better than simple Markov chains. A new solution to the problem of word overlap is proposed. It was found that the expected frequency and overlapping properties determine most of the variance. The expectation and variance of counts for triplets are compared with experimental counts in Escherichia coli coding sequences. PMID- 1422877 TI - METASIM: object-oriented modelling of cell regulation. AB - Enzymatic processes and substances are modelled as distinct objects, belonging to a limited number of classes. A set of class definitions in C++ is presented that constitutes an object-oriented programming platform. The latter supports 'biological' data types and functions and facilitates simulation of metabolic and regulatory pathways in living cells. To compute the time-evolution, Euler or Runge-Kutta methods are used, though the latter method compromises a strict object-oriented philosophy. As an example, histone gene expression during embryogenesis of Xenopus laevis is modelled. This object-oriented programming system forms a modelling 'language' which is readily understood by both biochemists and programmers. It allows biological problems to be programmed more easily and correctly and brings the program closer to the biological reality, hence making it more meaningful to bioscientists. Moreover, it can readily be extended to new models by class derivation. PMID- 1422878 TI - ADSP--a new package for computational sequence analysis. AB - A new protein sequence analysis package, ADSP, is described, of which the SOMAP Screen-Oriented Multiple Alignment Procedure forms an integral part. ADSP (Algorithms and Data Structures for Protein sequence analysis) incorporates facilities to generate potent pattern-recognition discriminators and offers four algorithms with which to scan any NBRF format sequence database: the package has been designed, in particular, to interface with the OWL composite sequence database, one of the largest, distributed non-redundant sources of sequence data of its kind. The system incorporates a powerful method for compound feature analysis, which provides the basis for characterizing and predicting the occurrence of complete protein superfamilies and for pinpointing the emergence of related sub-families. Used iteratively, the approach allows diagnostic performance to be rigorously refined and its efficacy to be assessed both qualitatively and quantitatively, and results in the generation of refined structural or functional features suitable for entry into a database: this compilation of characteristic signatures is distinct from, but complementary to, widely used compendia of pattern templates such as PROSITE. PMID- 1422879 TI - Clustering cDNA sequences. AB - A set of programs has been written to quantify the similarities between large numbers of cDNA sequences. This information is used to cluster similar sequences together. The main program can cluster thousands of cDNA sequences per day using a novel, computationally inexpensive algorithm. The clustering information is kept in a small index file so that disk storage requirements are negligible. Using this index file, subsidiary programs create various views and statistical summaries of the entire cDNA sequence collection. PMID- 1422881 TI - Limitations of Augustinsson plots. AB - The Augustinsson plot transforms the Michaelis-Menten equation by graphing velocity, v, as a function of velocity/substrate, v/s. The plot is linear with a negative slope for a single class of saturable sites and curvilinear for multiple classes of sites. Statistically, Augustinsson plots suffer from the limitation that there is no true independent variable. Experimental errors form a Gaussian distribution that rests neither parallel to the v axis nor v/s axis, but rather along a line emanating from the origin. Widening the range of s values produces increasingly large errors in the calculated Km and Vm values, especially when multiple sites are present. Exact data containing no error produces accurate constants using either the Michaelis-Menten or Augustinsson equation. With Km and Vm constants previously derived by fitting data with the statistically valid Michaelis-Menten equation, the Augustinsson plot may be used accurately to display multiple site data. PMID- 1422880 TI - CMAP: contig mapping and analysis package, a relational database for chromosome reconstruction. AB - In the contig mapping and analysis package, CMAP, we provide a foundation for reverse genetics by organizing information about DNA fragments obtained from an organism's genome into a physical map. The user can store information about a particular segment of DNA. This information can be both descriptive, such as any genes contained in a particular DNA fragment, or experimental, such as hybridization profiles or restriction digest patterns for comparison with other fragments. The package can then be instructed to update the physical map or provide information on a DNA fragment within the map, such as its location. The user interface is designed to minimize the learning curve associated with database usage, while eliminating the possibility of entering data outside the ranges of fields through error-checking protocols. Queries are currently accomplished by the use of dynamic SQL (structured query language), which gives the user the ability to build queries based on any combination of the attributes contained within the database without requiring that all possible queries be permanently programmed within the query software. In order to eliminate the need for knowledge of SQL, an interface was designed to allow users to build queries by menu choices. Thus, CMAP is a software package supporting a database for both the production and storage of a physical map as well as being the first step toward the production of a physical mapping workstation. PMID- 1422882 TI - Aligning two sequences within a specified diagonal band. AB - We describe an algorithm for aligning two sequences within a diagonal band that requires only O(NW) computation time and O(N) space, where N is the length of the shorter of the two sequences and W is the width of the band. The basic algorithm can be used to calculate either local or global alignment scores. Local alignments are produced by finding the beginning and end of a best local alignment in the band, and then applying the global alignment algorithm between those points. This algorithm has been incorporated into the FASTA program package, where it has decreased the amount of memory required to calculate local alignments from O(NW) to O(N) and decreased the time required to calculate optimized scores for every sequence in a protein sequence database by 40%. On computers with limited memory, such as the IBM-PC, this improvement both allows longer sequences to be aligned and allows optimization within wider bands, which can include longer gaps. PMID- 1422883 TI - A finite-difference computer model of solute diffusion in bacterial films with simultaneous metabolism and chemical reaction. AB - This finite-difference computer model is designed to simulate complex diffusion/reaction events in bacterial films. It is modular, each module mirroring closely a particular physical, chemical or biochemical factor. It is capable of handling > 20 diffusing/reacting species, but can be easily expanded or simplified to match particular systems. It was originally designed for modelling the events in dental plaque leading to tooth decay, but should find application in other fields. It allows for ion-exchange interactions with, for example, fixed charges on bacterial surfaces, which can act as pH and cation buffer sites. pH-dependent utilization of substrate is modelled implicitly, combining Michaelis-Menten kinetics with diffusion in a single iterative procedure. Advantages are given for computing diffusion of all other species explicitly using single-species diffusion coefficients, with charge-coupling by means of the algorithm Q-COUPLE. Activity corrections and enzyme pH-dependence are included. Chemical equilibria and mineral deposition/dissolution are computed iteratively node by node. The program is tested against some problems having analytical solutions, and an example is given of its application to demineralization of teeth as a result of bacterial action in dental plaque. PMID- 1422884 TI - MATCH-BOX: a fundamentally new algorithm for the simultaneous alignment of several protein sequences. AB - Original algorithms for simultaneous alignment of protein sequences are presented, including sequence clustering and within- or between-groups multiple alignment. The way of matching similar regions is fundamentally new. Complete matches are formed by segments more similar than expected by random, according to a given probability limit. Any classic or user-defined score matrix can be used to express the similarity between the residues. The algorithm seeks for complete matches common to all the sequences without performing pairwise alignment and regardless of gap weighting. An automatic screening delineates all the similar regions (boxes) that may be defined for a given maximal shift between the sequences. The shift can be large enough to allow the matching of any region of a sequence with any region of another one. It can also be short and used to refine the alignment around anchor points. The algorithm provides the most likely optimal alignment and a comprehensive list of the alignment dilemma. Duality between automatism and interactivity is provided. Depending on the problem complexity, a final alignment is obtained fully automatically or requires some interactive handling to discriminate alternative pathways. PMID- 1422885 TI - Dynamic programming algorithms for restriction map comparison. AB - For most sequence comparison problems there is a corresponding map comparison algorithm. While map data may appear to be incompatible with dynamic programming, we show in this paper that the rigor and efficiency of dynamic programming algorithms carry over to the map comparison algorithms. We present algorithms for restriction map comparison that deal with two types of map errors: (i) closely spaced sites for different enzymes can be ordered incorrectly, and (ii) closely spaced sites for the same enzyme can be mapped as a single site. The new algorithms are a natural extension of a previous map comparison model. Dynamic programming algorithms for computing optimal global and local alignments under the new model are described. The new algorithms take about the same order of time as previous map comparison algorithms. Programs implementing some of the new algorithms are used to find similar regions within the Escherichia coli restriction map of Kohara et al. PMID- 1422886 TI - GCWIND: a microcomputer program for identifying open reading frames according to codon positional G+C content. AB - GCWIND is a microcomputer (IBM-PC compatible) program for the identification of protein-coding open reading frames. The program is similar to the FRAME program, but the latter has only been implemented for a specialized graphics package. The base compositions (%G+C) for each of the three possible reading phases through the DNA sequence are displayed separately, together with the positions of potential translation initiation and termination codons (on the leading and complementary strands), to provide an immediate representation of those regions within the sequence that have coding potential. PMID- 1422887 TI - ANAGEL: a personal computer program for evaluating DNA fragment lengths from distances migrated in an agarose gel. PMID- 1422888 TI - Cisplatinum in combination with 5-fluorouracil and citrovorum factor in the treatment of advanced colorectal carcinoma. AB - A phase II trial of citrovorum factor, 500 mg/m2/week, plus 5-fluorouracil, 400 mg/m2/week on day 1, and cisplatin, 20 mg/m2/week on day 2, was carried out in a group of 40 patients with metastatic colorectal carcinoma. A partial response with a mean duration of 8.4+ months was achieved in 24% of patients, a minimal response with a mean duration of 5.4 months was obtained in 6% of patients, and a stabilization of 6.2 months was achieved in 41%. Ten patients (29%) progressed. A 38% partial response rate was seen in patients with advanced rectal carcinoma, whereas no response was obtained in patients with colon cancer. Interestingly, 5 partial responses were seen in 12 patients pretreated with 5-fluorouracil. The overall survival was 9.8+ months. The mean survival of patients who achieved a partial response was 12.0+ months, whereas patients who progressed survived a mean of 6.6+ months. Patients with colon cancer had a mean survival of 8.1+ months, and those with rectal cancer survived a mean of 11.1+ months. This difference was not statistically significant. The treatment was generally very well tolerated, with patients showing mostly grade 1-2 gastrointestinal and/or hematological toxicity. PMID- 1422889 TI - Efficacy of the combination of carboplatin and cyclophosphamide in the treatment of metastatic insulinoma. PMID- 1422890 TI - Immune senescence: mechanisms and clinical implications. AB - There are many changes in the immune response with age, most of which can be related to the involution of the thymus gland and alteration of the distribution and function of T lymphocytes. These changes indirectly influence B-cell function, which not only amplifies the immune deficits, but leads to the increased production of autoantibodies and monoclonal immunoglobulins with age. Thus, immune senescence is characterized by both an immune deficiency and an immune dysregulated state. PMID- 1422891 TI - Chemical radiosensitizers in cancer therapy. AB - The development of effective low-LET radiation therapy for cancer has been hindered by the lack of consistent differential responses to radiation between tumor and normal tissues. One major difference between many solid tumors and the surrounding normal stroma is the presence of hypoxic foci in solid tumors due to the inadequate supply of nutritional needs as a result of the breakdown of microvasculature. Consequently, failure of conventional radiotherapy and local recurrences are in part attributed to the radioresistant hypoxic cell populations, present in the tumor. Local cure/control rates of a tumor can be increased only by an effective increase in the radiation dose. At the same time, an increase in such a dose would damage the oxic normal stroma, more than the hypoxic tumor cells. Hence, specific modification of tumor radiosensitivity by the use of chemical radiosensitizers, in combination with conventional radiotherapy, is an attractive alternative. Many clinicians and radiotherapists are skeptical about the outcome of using radiosensitizers in patients. Nevertheless, a vast amount of information is currently available regarding the first- and second-generation radiosensitizers both in murine and in human tumors. As a result, it is hoped that eventually a radiosensitizing drug would be discovered/synthesized that will overcome the drawbacks so far encountered in their use in the clinic. In this article, the development of chemical radiosensitizers since the early sixties, the basis for their selection, their mechanism(s) of action, and the results obtained with the various groups of radiosensitizers are reviewed. PMID- 1422892 TI - Forensic DNA analysis: scientific, legal, and social issues. PMID- 1422893 TI - Nonsurgical approach in stage I and stage II breast cancer. PMID- 1422894 TI - Tamoxifen in axillary node--negative breast cancer: multisystem benefits and risks. AB - Adjuvant tamoxifen therapy is associated with modest improvement in disease-free and overall survival in women with invasive axillary node-negative breast cancer. The preponderance of data supporting these general conclusions are from trials in postmenopausal women; in premenopausal women data appear convincing regarding disease-free, but not overall, survival. Firm conclusions regarding magnitude of benefit related to presence of different prognostic factors cannot be drawn at present. In postmenopausal women tamoxifen appears to alter favorably some risk factors for cardiovascular diseases and osteoporosis, which are the most common causes of mortality or morbidity in older American women. Adjuvant tamoxifen is associated with a significantly reduced risk of second primary breast cancer. Major serious risks of tamoxifen therapy include depression, and possibly thrombophlebitis and uterine endometrial cancer. Symptomatic vasomotor and gynecological side effects are frequent. Decision making with women should include assessment of these multisystem benefits and risks. PMID- 1422895 TI - Adjuvant chemotherapy for node-negative breast cancer. PMID- 1422896 TI - Best papers on ovarian cancer. PMID- 1422897 TI - Best papers on leukemia. PMID- 1422898 TI - Gene therapy and cancer: is it for everybody? PMID- 1422899 TI - [Transduction of the visual signal in retinal cells]. AB - Transduction of a visual signal is a complex process. It involves photochemical, enzymatic and ionic reactions. An electrophysiological response is generated on absorption of a photon by a photoreceptor cell's pigment molecule, then propagates to the synapses. The first photochemical reaction, isomerization of retinal, in vertebrates occurs in the photoreceptor cells--rods and cones--of the retina, so changes conformation and activity of a pigment-bound protein, rhodopsin, in membranes of intracellular discs. Rhodopsin becomes enzymatically active and catalyses the activation by GTP of a great number of transducins, which in turn activate cGMP phosphodiesterase. This enzymatic chain propagates and greatly enhances hydrolysis of cytoplasmic cGMP. One photon incites hydrolysis of 10(5) cGMP molecules in 100 ms. Local cGMP decrease frees it from specific binding sites in cytoplasm occupied by proteinaceous canals in cell membrane around the activated disc. In darkness high cGMP concentration, hence binding, kept canals open, maintaining high cellular cation permeability, especially to Na+, and a strong cellular depolarization. Ca2+ influx, also allowed, balanced Na+ movement. Canal closure induces local hyperpolarization, the first electrophysiological response, which propagates through the cell to synaptic contacts. It also lowers intracellular Ca2+ concentration which initiates cGMP synthesis--from GTP by a guanylate cyclase controlled negatively by recoverin, a calcium-dependent protein--to restore cGMP towards at rest level. Although all macromolecules involved in this now fairly complete scheme have been isolated and characterized, cloned and sequenced, no three-dimensional structure has yet been established. The proteins are membrane-bound rather than in independent crystal form, which renders such structural studies difficult.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422900 TI - Multi-enzyme complexes associated with receptors during signal transduction. PMID- 1422901 TI - Receptors for pituitary glycoprotein hormones. PMID- 1422902 TI - Mechanism of action of steroid hormones and anti-hormones. A 1991 mini-overview. PMID- 1422903 TI - The immunoglobulin superfamily in cell surface recognition. PMID- 1422904 TI - The T cell repertoire in response to foreign and self-antigens. PMID- 1422905 TI - The Non Obese Diabetic (NOD) mouse, as a model of T cell mediated autoimmune disease. PMID- 1422906 TI - Mechanisms of gene activation in early vertebrate development. PMID- 1422907 TI - Cellular interactions during the ontogeny of neural crest derivatives. PMID- 1422908 TI - Adhesion systems in the Xenopus blastula. PMID- 1422909 TI - Environmental factors and the stability of differentiation in mammalian development. PMID- 1422910 TI - Early signals in the action of neuropeptide growth factors. PMID- 1422911 TI - Electrical and chemical communication in the early nervous system. PMID- 1422912 TI - Kinetics of activation, deactivation and desensitization of the "NMDA" glutamate receptor. PMID- 1422913 TI - The quantal synaptic unit in the central nervous system: a template for neuronal plasticity. PMID- 1422914 TI - Roles and actions of neuropeptide messengers; insights from studies with FMRFamide-related peptides and molluscan neurones. PMID- 1422915 TI - Functional organisation of the nicotinic acetylcholine receptor. PMID- 1422916 TI - [Activity of polar glycopeptidolipids from Mycobacterium chelonae in the reversal of chemically induced leukopenia in mice]. AB - Intraperitoneal administration of polar glycopeptidolipids extracted from Mycobacterium chelonae (GPLp-Mc) has led to reversal of Doxorubicin-induced leucopenia in a manner comparable to that effected by GM-CSF administered in a dose of 100 IU (2.5 micrograms/kg). The mode of action and the toxicity of this product are being studied. Results obtained on the mouse indicate that it would be worthwhile to undertake tests in man aimed at studying the effect of GPLp-Mc on chemotherapy- and radiotherapy-induced leukopenias, once toxicological studies have been carried out. PMID- 1422917 TI - [Metabolic effects of phosphate receptors stimulating the ileal transport of calcium]. AB - Several compounds, either metabolizable such as sorbitol and creatine or unmetabolizable such as L-xylose or ethyl-ethanolamine, increase ileal calcium transport, similarly to the well documented effect of lactose. These compounds increase the duration time but not the rate of calcium transport. They have no specific effect on intestinal calcium absorption but they prolong the presence of soluble calcium in the ileal loop, thus allowing the calcium absorption. This stimulating effect of these compounds on mineral absorption is associated with an increase of ileal mucosal ATP content. PMID- 1422918 TI - [Description of a tissue culture technique using tissue from mussel (Mytilus edulis) for the preparation of chromosomes]. AB - Explants from mantle and foot tissues of adult mussel were grown in culture tubes containing a medium composed of Eagle's Basal Medium supplemented with salts, Hepes buffer, egg yolk and antibiotics. The cultures were maintained at 18 degrees C and pH 7.50, without medium renewal. After 6-7 days, the cultures were stopped and harvested for slide preparation. Numerous metaphase spreads that were good enough for karyotyping were consistently obtained. This method may prove to be a reliable source of actively dividing cells that is a prerequisite for extensive chromosome structure analyses in the bivalves. PMID- 1422919 TI - [Mollicute Acholeplasma florum possesses a gene of phosphoenolpyruvate sugar phosphotransferase system and it uses UGA as tryptophan codon]. AB - Acholeplasmas are mollicutes which do not require sterol for growth and do not possess a phosphoenolpyruvate-dependent sugar-phosphotransferase system. In contrast to spiroplasmas, mycoplasmas and ureaplasmas, they utilize UGA as a stop codon and not as a tryptophan codon. Acholeplasma florum, because of its metabolic properties and its close phylogenetic relationship to members of the genera Spiroplasma and Mycoplasma, does not seem to be an acholeplasma senso stricto. Here, we present molecular data to support this hypothesis. We have detected a gene coding for one of the components of the phosphotransferase system (PTS) in A. florum. In addition we demonstrate that the organism uses UGA as a tryptophan codon and not as a stop codon. These findings offer strong evidence, along with an earlier phylogenetic proposal, that A. florum is not a member of the genus Acholeplasma. PMID- 1422920 TI - [Spatial memory of Meriones libycus (Rodienta, Gerbillidae)]. AB - Meriones libycus, a desert rodent with a large home range, has a good spatial memory over at least 90 days, which makes it able to travel for a long way and come back to its nest. Males have a better spatial memory than females. PMID- 1422921 TI - An enzymatic determination of hydrogen peroxide by using spectrophotometry. AB - A new spectrophotometric method for determining low hydrogen peroxide concentrations by using horseradish peroxidase in the presence of NADH at pH 7.5 has been described. Both total NADH consumption and initial reaction rate may be used for the determination. Using the NADH consumption, a linear response with respect to hydrogen peroxide was observed in the concentration range 7 x 10(-8) 2.5 x 10(-6) M. Due to the presence of superoxide dismutase, hydrogen peroxide is partly regenerated and an amplification of the signal results, which explains the sensitivity. PMID- 1422922 TI - [Respective role of mifepristone (RU486) binding to blood and tissue proteins in its quantitative distribution in the body]. AB - In plasma, mifepristone (RU486)-alpha 1-glycoprotein acid (AGP) interaction follows a quickly saturable process within the range of therapeutic concentrations. The high affinity to AGP, Kap = 8 x 10(6) M-1, suggests that the tissue distribution of the drug is possibly impaired. Checking this hypothesis was done by simulating its body distribution between plasma proteins and tissues. Two methods were used. The first was to calculate the number of available binding sites in both plasma (Np) and tissues (NT), to measure the relevant association constants Kap and KaT, and to consider that mifepristone partitioned according to their ratios, expressed as [NpKap]/[NpKap + NTKaT] for the plasma and [NTKaT]/ NpKap + NTKaT] for the tissues. The second method used equations relating the apparent volume of distribution and the plasma unbound fraction of mifepristone with volumes of physiologic spaces to calculate the percentage of drug located in plasma, extracellular and intracellular fluids. The results yielded by the two methods are close. They show that with AGP levels within a normal range (18.4 microM), only 18% of mifepristone is bound to AGP and the remaining part 82% is located in tissues. By contrast, when AGP level dramatically increases (300 microM) most of the dose (77%) is retained in plasma. These results suggested that when AGP concentration increases, the efficacy of therapeutic concentration of mifepristone may be partially decreased if only the unbound fraction of this synthetic hormone were biologically active. PMID- 1422923 TI - Inhibition of sulfur mustard-increased protease activity by niacinamide, N-acetyl L-cysteine or dexamethasone. AB - The pathologic mechanisms underlying sulfur mustard-induced skin vesication remain undefined. Papirmeister et al. (1985) have postulated a biochemical mechanism for sulfur mustard-induced cutaneous injury involving DNA alkylation, metabolic disruption, and enhanced proteolytic activity. We have previously utilized a chromogenic peptide substrate assay to establish that human peripheral blood lymphocytes exposed to sulfur mustard exhibited enhanced proteolytic activity. In this study, compounds known to alter the biochemical events associated with sulfur mustard exposure or to reduce protease activity were tested for their ability to block the sulfur mustard-increased proteolysis. Treatment of cells with niacinamide, N-acetyl-L-cysteine, or dexamethasone resulted in a decrease of sulfur mustard-increased protease activity. Complete inhibition of sulfur mustard-increased proteolysis was achieved by using protease inhibitors (antipain, leupeptin, and 4-(2-aminoethyl)-benzenesulfonylfluoride). These data suggest that therapeutic intervention in the biochemical pathways that culminate in protease activation or direct inhibition of proteolysis might serve as an approach to the treatment of sulfur mustard-induced pathology. PMID- 1422927 TI - Methods of postoperative pain control. PMID- 1422926 TI - Toxic effects of sulfur mustard on respiratory epithelial cells in culture. AB - Sulfur mustard (SM) is known to induce cutaneous injury and to cause acute damage to the respiratory tract. Although skin vesication has been demonstrated on human epidermal keratinocytes in culture, no study has been carried out to analyze the effects of SM on the ultrastructural and functional activity of surface respiratory epithelial cells. To evaluate this SM toxicity, we developed an in vitro model of respiratory epithelial cells in primary culture. The study was performed on surface epithelial cells from rabbit trachea cultured according to the explant-outgrowth technique. The functional activity of the cultures was evaluated by measuring the ciliary beating frequency (CBF) of the ciliated cells with a videomicroscopic method. The morphological aspects of the cells were analyzed by light and electron microscopy. Addition of 0.1 mM SM directly into the culture medium produced a sudden and irreversible CBF inhibition, first observed after 2 hr on the ciliated cells of the outgrowth periphery. The arrest of the ciliary beating progressively reached the whole surface of the outgrowth and was simultaneously observed with a detachment of the outgrowth cells. It began at the outgrowth border, leading to the exfoliation of cell sheets, and then to the whole culture after 48 hr. Morphological damage was expressed by intense vacuolisation and disorganization of cytoplasmic and nuclear structures. These findings suggest that the detachment of the respiratory epithelial cells from the matrix represents a major toxic effect of 0.1 mM SM. SM dramatically affects the viability of respiratory epithelial cells in culture. Moreover, the sudden CBF inhibition is more likely due to the death of the ciliated cells than to a specific ciliotoxic effect of SM. PMID- 1422925 TI - Comparison of in vivo acute lethal potency and in vitro cytotoxicity of 48 chemicals. AB - The cytotoxicity of 48 compounds included in the MEIC (Multicenter Evaluation of In Vitro Cytotoxicity) list was determined in cultures of rat hepatocytes, McCoy, and MDBK cells. The average minimum concentration of each compound inducing cytotoxicity was measured in each cell type. The cytotoxicity values were then compared with published oral LD50 values for rats and mice. The logarithmic transformation of in vivo toxic doses and the corresponding in vitro cytotoxic concentrations showed a statistically significant correlation between the in vitro and in vivo values. The results show that an accurate in vivo LD50 dose could be predicted from in vitro data for at least 75% of the selected compounds. It is hoped that this finding will not only stimulate others to pursue in vitro technique but will eventually lead to elimination of the in vivo LD50 test. PMID- 1422924 TI - Expression of heat shock-regulated human growth hormone genes containing or lacking introns by NIH-3T3 and Wish cell lines. AB - A plasmid containing the complete genomic DNA of the human growth hormone (ghGH) comprising four introns and driven by the human promoter of the human gene of the 70 kDa heat shock protein (hsp70) has been used to transfect mouse NIH-3T3 and human Wish cells. Selected cell lines were characterized for stable hGH secretion. Similarly in the same NIH-3T3 cells, the stable expression of the same plasmid construct, but containing the complementary DNA of the hGH gene (chGH), was compared in terms of the effect of introns on heterologous protein synthesis. Genomic hGH recombined cells synthetized, in a heat regulated fashion, matured hsp70/hGH hybrid mRNA able to drive the secretion of a 22 kDa polypeptide. Like the natural hGH, this polypeptide expressed the functional hormonal activity of prolactin on casein secretion by mammary cells. The time course of hGH secretion was prolonged in ghGH transcripts, while that of mRNA degradation appeared delayed, especially in Wish cells, as compared to chGH expression. In the human Wish cells the decay of endogenous hsp mRNA has been compared to that of recombinant hsp mRNA, demonstrating that this human hsp70/hGH hybrid mRNA was present in the cytoplasm during a longer period than the human endogenous hsp70 mRNA. In conclusion, similar levels of expression and resulting gene products were expressed from the chGH or the ghGH gene in an inducible manner. PMID- 1422928 TI - [Famotidine does not modify the plasma levels of lidocaine for spinal anesthesia. A comparative study of famotidine and cimetidine]. AB - H2 receptor antagonists are often used to reduce gastric acidity prior to general or regional anaesthesias. However cimetidine and ranitidine have been found to increase plasma levels of local anaesthetics such as lidocaine. This study aimed to compare famotidine--another H2 receptor antagonist--with cimetidine in this respect. 33 male patients 70 years old or more, scheduled for surgery under spinal anaesthesia and randomized into 3 groups, received either diazepam 0.15 mg.kg-1 and famotidine 20 mg (group A) or diazepam and cimetidine 200 mg (group B) or diazepam only (group C) on the previous night and 90 minutes before spinal anaesthesia by hyperbaric lidocaine 5%, 3 ml. Arterial blood samples were taken 3 minutes after spinal injection then every 15 minutes unto 90 minutes after the first sampling. Lidocaine plasma levels were measured by fluorescence polarization immunoassay and the results were statistically analyzed. In famotidine group lidocaine levels were intermediate between B and C groups levels, and the increase was of lesser duration than in B group. Elimination mechanism of lidocaine with and without H2 inhibitor is briefly discussed. Therefore famotidine would appear to be more convenient than other H2 receptor inhibitors whenever antacid protective effects are sought after prior to regional anaesthesia. PMID- 1422929 TI - [A comparative study of the cost of open-circuit as opposed to closed-circuit ventilation]. AB - The authors compared two open randomized groups of patients undergoing surgery through general anaesthesia. Group 1 consisted of 54 patients ventilated by a Siemens 900 B ventilator in open circuit, and group 2, 56 patients ventilated by an ELSA de Gambro ventilator in a closed circuit. Comparative hour cost for nitrous oxide (N2O), oxygen (O2) and halogen gas, Enflurane, Isoflurane, was noted. All patients received the same regimen of anaesthesia and the two groups were identical in age, weight, surgery, respiratory volume and ventilation time. The evaluation of comparative hour cost included specific materials of close circuit ventilator: CO2 filter (Aridus), Lime. Were excluded maintenance and gas consumption expenditures before patient connected to the ventilator. The total hour cost (O2, N2O, specific materials for close circuit, without halogen gas) was 8.23 FF in closed circuit against 13.28 FF in open circuit, an economy of 38.27%. Hence, for oxygen, the hour cost was 0.70 FF in open circuit against 0.27 FF in closed circuit (gain of 65.3%). For nitrous oxide, the hour cost in open circuit was 12.50 FF against 2.44 FF in closed circuit (80.5%). For Isoflurane, the open circuit hour cost was 41.38 FF against 22.44 FF in closed circuit (47%). For Enflurane, the open circuit hour cost was 14.17 FF against 5.94 FF in closed circuit (58.1%). And, lastly for Enflurane, open circuit hour cost was 14.17 FF against 5.94 FF in close circuit, gain of 58.1%. These "modest" economy against those found in previous studies can be explained by the long-time duration of ventilation, saturating time in open circuit more or less long, depending on the physician, specific materials for closed circuit ventilation--lime, CO2 filter- in not taken into account, the hour cost of O2 + NO2 goes from 8.23 FF to 2.71 FF, and the gain against the close circuit becomes 79.6%: reducing hour cost by 5 times. In order to improve the effective cost of close circuit, the authors proposed: the use of closed circuit ventilation for more than 3 hours surgery, gas saturation in closed circuit after denitrogenation--which demands the use of halogen infjectors, and lime in containers cheaper than disposable cartridges. Respecting the above criteria, the total hour cost in close circuit fell to 4.90 FF, gain of 63% against open circuit. For O2 et N2O, the hour cost goes from 1.34 FF in close circuit to 13.28 FF in open circuit, 90% economy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422930 TI - [Severely burned patients and atracurium: the train-of-four response]. AB - Severely burned patients show a relative hyposensitivity to atracurium. The neuromuscular block obtained in 20 patients with major thermal injury after 0.75 mg.kg-1 i.v. of atracurium, by muscular activity recording (train of four-TOF), was studied. The results confirmed the resistance to atracurium, which mechanism is unknown. Even the doses administered, 50% higher than clinical dose (0.3-0.5 mg.kg-1), proved insufficient in order to obtain a complete neuromuscular block in severely burned patients. PMID- 1422931 TI - [The effect of the local anesthetic temperature on spinal anesthesia using 0.5% bupivacaine]. AB - The aim of this study was to compare spinal anaesthesia with 0.5% bupivacaine at 20 degrees C and 5 degrees C. One hundred two patients ASA I-II were randomized into two groups. After atropine and IV fluid administration, patients of group I received intrathecally at L3-L4 level 0.02 ml.cm-1 of plain 0.5% bupivacaine at 20 degrees C, while patients of group II received the same solution and the same doses but at 5 degrees C. No significant difference was found between the times for installation of sensory and motor blocks nor between the durations of motor block in the two groups. On the other hand significant differences were found between the durations of sensory block in group I (283.33 min +/- 9.40 min) and group II (314.35 +/- 8.80 min) (P < 0.001) and all the more (P < 10(-9)) between the cephalad block extensions in group I (D 7.45 +/- 0.14) and group II (D 4.82 +/- 0.20). Therefore plain bupivacaine 0.5%, isobaric at 20 degrees C, seems to get the properties of an hyperbaric solution when cooled at 5 degrees C. PMID- 1422932 TI - [The intravascular transfer of glycine during percutaneous kidney surgery]. AB - Transurethral prostatic resection using a 1.5% glycine solution causes a well known clinical and metabolic syndrome called TURP-syndrome. Recent development of percutaneous renal surgery is responsible of several similar accidents. In a prospective study of 150 patients (mean age: 35 +/- 10) subjected to a percutaneous nephrolithotomy, the natremia and the amino acid content of the plasma were measured preoperatively and immediately postoperatively by chromatography. The study shows that there is a post-nephrolithotomy syndrome in two per cent. This syndrome contains a hemodilution with hyponatremia and reabsorption of irrigation fluid. Glycolemia, serinemia and threoninemia increase significantly. These modifications have a good correlation between them except for the natremia. Variability of results in this study and in the literature is explained by difficulty and duration of surgery, volume of glycol used, increasing intrarenal pressures and sudden opening of vessels peroperatively. The gravity of post-nephrolithotomy syndrome requires to change the irrigate solute and use normal saline solution when it is possible. PMID- 1422933 TI - [The importance of neurologic monitoring in anesthesiology]. AB - Owing to the recent advances of bioelectric signals computerized treatment a real monitoring of anaesthesia is now possible, either by EEG or by classical or event related evoked potentials methods. Available methods and their indications and difficulties are discussed with the help of some clinical examples. PMID- 1422934 TI - [Practical aspects of the laryngeal mask]. AB - The laryngeal mask (LM) is increasingly used. An overview is made: description, insertion, cardiovascular responses, advantages, LM and aspiration, LM as an aid to ventilation, indications, LM in difficult intubations, contra-indications, sterilization and cost. PMID- 1422936 TI - [Is it necessary to generalize the anesthesia record?]. PMID- 1422935 TI - [Rupture of the diaphragm in a closed injury of the thorax. Reflections apropos of a case]. PMID- 1422937 TI - [Renewal of qualifications in the United States]. PMID- 1422938 TI - Pictorial keys for the identification of domestic mites. PMID- 1422939 TI - Paracetamol anaphylaxis. AB - We describe four cases of anaphylaxis to paracetamol without co-existing aspirin intolerance and review the Australian experience in paracetamol anaphylaxis. Paracetamol sensitivity may differ in the mechanism from sensitivity to aspirin and other non-steroidal anti-inflammatory drugs as previously believed. PMID- 1422940 TI - Lability in complement receptor mobilization of granulocytes in patients with bronchial hyperreactivity. AB - The recruitment of activated granulocytes to bronchial mucosa seems to be involved in the prolonged inflammatory response observed in asthma and probably associated with bronchial hyperresponsiveness. We studied the patients with bronchial hyperresponsiveness with respect to the expression of complement receptor type 1 (CR1), its variability and readiness to become mobilized on peripheral granulocytes from patients with bronchial hyperresponsiveness. CR1 expression and its hourly variation was significantly (P less than 0.02, P less than 0.01 respectively) higher in the patient group compared with the control group. In addition the ability to mobilize CR1 spontaneously at +37 degrees C correlated to the variation of CR1 expression that occurred during a 4 hr period. These findings indicate that granulocytes from patients with bronchial hyperresponsiveness have a higher degree of variation in CR1 expression that correlates to their ability to mobilize CR1 and may reflect a more pronounced lability. PMID- 1422941 TI - Longitudinal variability of skin prick test results. AB - The skin prick test (SPT) is a commonly used procedure for assessing a specific sensitization. The longitudinal variability of test results is of interest for clinical as well as epidemiological investigations. The sensitization to four common aeroallergens (grass pollen, birch pollen, Dermatophagoides pteronyssinus, cat dander) is investigated within the framework of three consecutive SPTs at 11 month intervals for a population of 587 schoolchildren. The prevalence of sensitization based on a weal diameter of at least 2 mm was between 12.9% (cat dander) and 23.9% (grass pollen) in the initial testing. The positive predictive values of the initial SPT were between 75.3% (birch pollen) and 88.2% (cat dander) for the two subsequent SPTs. In the case of initially negative tests with positive second and third SPTs the incidence ranged between 3.2% (cat dander) and 4.3% (birch pollen) per year. A clear increase in the intensity of reaction in subsequent tests was observed in a number of probands testing positively in the initial SPT. In conclusion, our data indicate a high long-term stability of a specific sensitization to aeroallergens in SPT. PMID- 1422942 TI - Urinary excretion of angiotensin I, II, arginine vasopressin and oxytocin in patients with anaphylactoid reactions. AB - Human urine samples, purified on octadecasilyl-silica cartridges, contained immunoreactive angiotensin I, II, arginine vasopressin and oxytocin. The daily excretion of these peptides in healthy volunteers was 190.00 +/- 38.43 (n = 12), 17.48 +/- 3.09 (n = 12), 63.43 +/- 14.84 (n = 8) and 13.52 +/- 1.42 (n = 7) pmol/24 hr, respectively (mean +/- s.e.m.). Patients with a history of anaphylactoid reactions to drugs or food additives showed clinical symptoms such as urticaria, flush, nausea, dizziness and hypotension after oral provocation with cyanocobalamine, propyphenazone, acetylsalicylic acid and sodium benzoate. In five of the seven patients, angiotensin I and II were increased several fold in the urine fractions after symptoms were reported. The average increase in the urine concentration of both peptides was fourfold and 5.5-fold. In three out of five patients, the mean excretion of arginine vasopressin and oxytocin immunoreactive material was also elevated by a factor of 5.7 and 4.4, respectively. Oral provocation with a placebo failed to elicit anaphylactoid symptoms or an increase in the urine levels of angiotensin I or angiotensin II. Angiotensin I and angiotensin II-like immunoreactivity could be characterized on HPLC as Ile5-angiotensin I, Ile5-angiotensin II and angiotensin II metabolites. HPLC characterization of immunoreactive arginine vasopressin and oxytocin in two different gradient systems showed retention times different than the retention times of the corresponding synthetic standard peptides indicating that both peptides are not authentic AVP and OXT. These results suggest that angiotensin I and angiotensin II may be involved in the clinical events observed during some forms of anaphylactoid reactions. PMID- 1422943 TI - Autologous bacteria induce chemotaxis of peripheral blood mononuclear cells (MNC) from non-atopic asthmatics. AB - The chemotactic response of peripheral blood MNC from healthy subjects and non atopic asthmatics against the respective pathogen isolated and cultured from sputum of individual patients was investigated. We found that the wide range of concentrations of autologous bacteria induced chemotaxis of MNC from asthmatics but showed no influence on MNC from healthy subjects. This finding might explain the mechanism of lymphocyte accumulation in the lungs of non-atopic asthmatics. PMID- 1422944 TI - Can asthma be cured? PMID- 1422945 TI - The control of allergens of dust mites and domestic pets: a position paper. PMID- 1422946 TI - Allergy. Conventional and alternative concepts. A report of the Royal College of Physicians Committee on Clinical Immunology and Allergy. AB - Allergy is an exaggerated response of the immune system to external substances. It plays a role in a wide range of diseases. In some, such as summer hayfever, the symptoms are due entirely to allergy. In other conditions, particularly asthma, eczema and urticaria, allergy plays a part in some patients but not all. In these situations, allergy may have either a major role or provide just one of many triggers. In an individual patient's illness, the importance of allergy may change with time. The most common allergens (substances causing allergy) are grass and tree pollens, the house dust mite, products from pets and other animals, agents encountered in industry, wasp and bee venom, drugs, and certain foods. Food allergy presents a particularly difficult problem. Some individuals who react to food suffer from food allergy in its strict sense but in others there is no evidence of an alteration in the immune system. Here the term 'food intolerance' is preferable. Conventional doctors treat allergy by allergen avoidance--where this is possible--and drugs that relieve symptoms. In a few selected cases, in which other methods have failed, immunotherapy (desensitisation or hyposensitisation) is recommended. Although patients who consult practitioners of alternative allergy may do so by preference, it is often also because they are dissatisfied with the conventional approach to diagnosis and treatment, or because they have conditions which conventional doctors do not accept as having an allergic basis. There is a very wide range of alternative approaches to allergy, including the methods used by clinical ecologists and other treatments such as acupuncture and homoeopathy. Hypnosis may have a small role to play in helping the asthmatic and similar effects have been suggested for acupuncture. Furthermore, it is likely that there are still many active ingredients in medicinal plants used by herbalists but these need to be clearly identified and purified before their usefulness can be evaluated properly. Apart from these situations, we have yet to be convinced by substantial evidence that any of the other alternative methods of diagnosing or treating allergic disease are of proven value. There have, however, been many false and misleading claims and serious harm may be caused by misdiagnosis or delays in appropriate treatment. The public should be warned against costly methods of diagnosis and treatment which have not been validated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1422947 TI - Secular trends in the incidence of postmenopausal vertebral fractures. AB - Several studies suggest secular increases in hip fracture incidence through this century, but little is known about such trends for vertebral fracture. We have examined changes in the incidence of clinically ascertained vertebral fractures among Rochester, Minnesota residents aged 35-69 years, that were first diagnosed between 1950 and 1989. Our results indicate no overall increase in incidence over the 40-year period. Categorization of fractures according to the level of preceding trauma, however, revealed a significant increase in the incidence of fractures following moderate trauma among women aged 60-69 years. This increase occurred between 1950 and 1964, and leveled off thereafter. Rates for severe trauma fractures among postmenopausal women, and for vertebral fractures from any cause among younger men and women, remained stable. The rise in moderate trauma fractures in postmenopausal women paralleled that for hip fractures in Rochester and began to plateau at around the same time. It might have resulted from increased diagnosis of vertebral fractures, but the increase in hip fracture incidence is inconsistent with this explanation. An increase in the prevalence of osteoporosis, however, might account for the trend in both types of fractures. PMID- 1422949 TI - Crystallographic lattice refinement of human bone. AB - X-ray diffraction studies on bone microsamples (human iliac crest of 87 individuals aged 0-90 years) reveal that certain crystallographic parameters such as unit cell volume of bone apatite, and half-width of (002)-reflection are well correlated with age and with type of tissue (corticalis and spongiosa). Similar to inorganic apatite, the lattice parameters of bone apatite are intensely affected by ionic substitutions and vary mainly due to exchange of hydroxyl- and carbonate-apatite and, to a minor extent, of fluor- and chlorapatite. PMID- 1422948 TI - Annual injection of vitamin D and fractures of aged bones. AB - In order to investigate the effect of a supplementation of vitamin D in the prophylaxis of fractures of the bones of aged people, an annual intramuscular injection of ergocalciferol (150,000-300,000 IU) was given to two series of aged subjects: first to 199 (45 male) of 479 subjects (110 male) aged more than 85 years who were living in their own home, and second to 142 (29 male) of 320 (58 male) subjects aged 75-84 and living in a home for aged people. This prospective series was divided into treatment groups according to month of birth. These injections were given annually from September to December in the years 1985-1989, two to five times to each participant. The fracture rates, laboratory values, vitamin D levels, possible side effects, and mortality were followed until October 1990. A total of 56 fractures occurred in the 341 vitamin D recipients (16.4%) and 100 in 458 controls (21.8%) (P = 0.034). The fracture rate was about the same in both outpatient and municipal home series. Fractures of the upper limb were fewer in the vitamin D recipients, 10/341 = 2.9% (P = 0.025), than in the controls, 28/458 = 6.1%, during the follow-up. A similar result was obtained in fractures of ribs, 3/341 = 0.9% and 12/458 = 2.6%, respectively. Fractures of the lower limbs occurred almost as frequently, 31/341 = 9.1%, among the vitamin D recipients as among the controls, 49/458 = 10.7%. The fracture rate was higher in females (22.2%) than in males (9.5%). The fractures were fewer in the vitamin D recipients only in females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422950 TI - Antiidiotypic PTH antibodies as a cause of elevated immunoreactive parathyroid hormone in idiopathic hypoparathyroidism, a second case: another manifestation of autoimmune endocrine disease? AB - A 69-year-old man became hypocalcemic under medical observation. The hypocalcemia occurred in the presence of circulating immunoreactive parathyroid hormone (PTH). Common causes of secondary hyperparathyroidism were excluded, as was PTH resistance using PTH infusions. The immunoreactive PTH was examined in detail. PTH immunoreactivity (1) was not retained on a C18 SPE-column, suggesting unusual molecular or physicochemical properties, unlike bona fide PTH; (2) was precipitated with 15% PEG, indicating a molecular size far in excess of native PTH; (3) had an apparent molecular size similar to immunoglobulins on size exclusion chromatography; (4) was retained on affinity chromatography with both Protein A and anti-hIgG antibodies. These data lead us to conclude that the immunoreactive PTH was due to antiidiotypic PTH autoantibodies. No significant quantities of true PTH were found in the patient's serum suggesting that his hypoparathyroidism was a result of PTH deficiency. Autoimmunity might explain the occurrence of both processes if an arrested antiidiotypic antibody cascade is assumed. PMID- 1422951 TI - Incorporation of sodium fluoride into cortical bone does not impair the mechanical properties of the appendicular skeleton in rats. AB - Clinical studies on the use of sodium fluoride (NaF) in osteoporotic patients have demonstrated increased spinal bone mass without a reduction in vertebral fracture incidence, and a trend towards reduced appendicular bone mass with an increase in peripheral fracture incidence. As previous reports have suggested that NaF becomes incorporated into bone's crystal structure, possibly affecting bone strength, we sought to examine the relationship among bone fluoride content, bone mass, and skeletal fragility. Twenty-one-day-old female Sprague-Dawley rats were treated with four different doses of NaF. The tibiae were subjected to histomorphometric and biochemical analyses, and the femora were tested in torsion for the properties of strength, stiffness, energy storage capacity, and angular deformation. The results showed that over 50% of the skeleton in these rats was turned over in the presence of NaF. The four different doses resulted in a linear increase in bone F concentration and suggested excellent absorption and incorporation of this drug. No changes in histomorphometric indices of bone formation or turnover were found. Despite the large fraction of bone formed during NaF treatment, and the linear increase in bone fluoride content in relation to dose, there were no changes observed in any of the mechanical properties. These results suggest that, even extensive incorporation of fluoride into bone, in the absence of an effect on bone mass or remodeling, does not significantly alter its capacity to withstand mechanical loads. PMID- 1422952 TI - Cultured embryonic bone shafts show osteogenic responses to mechanical loading. AB - Pairs of 17-day embryonic chick tibiotarsi were removed and maintained in organ culture. One of each pair was subjected to a single 20-minute period of intermittent loading at 0.4 Hz, producing peak longitudinal compressive strains of 650 microstrain (mu epsilon). In the 18-hour culture period following loading, alkaline phosphatase levels in the osteoblasts of the loaded tibiotarsi were maintained whereas in controls they declined. In situ hybridization using a collagen type I cRNA riboprobe showed a substantial increase in expression of mRNA for collagen type I in the periosteal tissue of bones that were cultured for 18 hours after loading compared with that in similarly cultured controls and bones cultured for 4 hours. These results demonstrate that appropriate loading of embryonic chick bones in organ culture elicits adaptive regulation of matrix synthesis as evidenced by increased expression of the gene for type I collagen and alkaline phosphatase activity. This model may be useful as it must contain all the obligatory steps between strain change in the matrix and modified osteogenic activity. PMID- 1422953 TI - Effect of a five-week swimming program on rat bone: a histomorphometric study. AB - To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swim training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2-6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. "Normal" gravity would be an important cofactor in the osteogenic effects of exercise. PMID- 1422954 TI - Competitive adsorption of magnesium and calcium ions onto synthetic and biological apatites. AB - Magnesium (Mg) is a conspicuous constituent of hard tissues but its possible role in biomineralization is poorly understood. It is possible that Mg2+ adsorbed onto bioapatites may contribute to the modulation of crystal growth as such inhibitory activity has been reported for synthetic apatites. The present study was undertaken to determine the adsorption isotherms of Mg ions onto synthetic apatites and biominerals in tooth and bone tissues in the presence of other ions of natural occurrence. Synthetic crystals used as adsorbents were hydroxyapatite and, as a better prototype for the biomineral, Mg-containing carbonatoapatite. Human enamel and dentin materials were obtained from extracted, caries-free, permanent teeth. Porcine dentin materials at two developmental stages were obtained from erupted deciduous and unerupted permanent teeth of a 6-month-old slaughtered piglet. Porcine bone was obtained from the cortical portion of the mandible of the same animal. All biomineral samples were pulverized and then treated by plasma ashing (deproteination) at about 60 degrees C. Each of the powdered samples was equilibrated in solutions containing various initial concentrations of Mg2+, Ca2+, and Na+ (or K+) as nitrate salts. Following equilibration, concentrations (and activities) of magnesium and calcium ions in the experimental solution were determined. The pH values of the equilibrium solutions were in the range of 6.2-6.5. Experimental data of the Mg adsorption onto hydroxyapatite were interpreted on the basis of a Langmuir-type model for binary systems assuming competition of Mg2+ and Ca2+ for the same adsorption sites on the crystal surfaces of the apatites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422955 TI - An active neutral metalloproteinase bound to the insoluble collagen in the mineralized phase matrix of adult rat calvaria. AB - Two kinds of proteinases were found in the mineralized phase matrix of 24-week old rat calvaria by means of enzymography using gelatin as a substrate. One proteinase was a neutral thiol 58kD proteinase as shown in a previous paper [2]. The other was a neutral metalloproteinase that had a molecular mass of 56kD and was detected only when calcium (Ca) ions were added to the incubation buffer. It is believed that the 56kD proteinase is bound to the insoluble collagen of the bone matrix, as it is solubilized by 4 M guanidine HC1 solution from the insoluble collagen fraction, when prepared by removing extractable proteins of the mineralized phase matrix. The insoluble collagen fraction could also be solubilized and prepared as gelatin by heating at 65 degrees C for 5 minutes. The gelatin was then incubated at 37 degrees C without further treatment and became degraded without an activation of 4-aminophenylmercuric acetate (APMA). This nonactivated degradation was enhanced by adding Ca ions. These results suggest that the 56kD metalloproteinase bound to the insoluble collagen of bone matrix is in an active form and may participate in the rapid degradation of collagen during bone resorption. As partially purified 56kD metalloproteinase degraded cartilage type proteoglycan, but not type I, IV, and V collagens, it is possibly related to the degradation of proteoglycans before it binds to collagen fibers during bone formation. PMID- 1422956 TI - Odontogenic tumors in mice carrying albumin-myc and albumin-rats transgenes. AB - Odontogenic tumors that produce abnormal tooth-like structures are repeatedly observed in mandibles of mice that carry both albumin-myc and albumin-ras transgenes. The earliest lesions appear among the periodontal ligament mesenchymal cells, but later lesions include an epithelial component. Subsequent tumor development recapitulates the process of normal tooth formation, which requires multiple sequential cell signals, and results in cell differentiation, matrix secretion, and mineralization. Tumor cells with epithelial morphology produce ras oncoprotein, consistent with an epithelial origin of these tumors. As albumin regulatory sequences direct oncogene expression in these mice, our findings also suggest that some of the albumin present in normal teeth may be locally produced and have a role in tooth mineral formation. The reproducibility of this phenotype makes these mice an excellent model for studies of both normal and neoplastic odontogenesis. PMID- 1422957 TI - Epidemiology and socioeconomic cost of osteoporotic fractures in Greece. PMID- 1422958 TI - Ability of vertebral dimensions from a single radiograph to identify fractures. AB - It has been proposed that vertebral dimensions be used to objectively identify vertebral fractures, permitting standardization of methodology for comparisons between studies. In this report, we evaluate the ability of various vertebral dimensions and ratios to identify "abnormal" vertebrae. As no "gold standard" exists for prevalent vertebral fractures, we examined the ability of cross sectional dimensions (at a single point in time) to detect fractured vertebrae that had been identified from changes in dimensions compared with previous radiographs. Theoretically, a cutoff of 3 SD below the mean will rarely misclassify normal vertebrae as fractured (specificity = 99.9%). However, we found that this cutoff correctly identified only about 70% of the incident fractures. A less stringent criterion (2 SD below the mean; theoretical specificity = 97.7%) identified about 85-90% of true fractures. Dividing by stature or other vertebral heights sometimes yielded marginal improvements in the ability of the anterior or posterior height dimensions to diagnose fractures. The results suggest that the true fracture prevalence may sometimes be substantially higher than suggested by cross-sectional vertebral measurements. PMID- 1422959 TI - The bone "quality" problem. PMID- 1422961 TI - Ultrasound attenuation of the calcaneus in the female population: normative data. AB - Broadband ultrasound attenuation (BUA) on the os calcis has been proposed as a safe and reliable technique for evaluating skeleted status. The present study provides preliminary normative BUA results on 93 female subjects divided into five age groups. These data can be used as a guide for comparing the results of individual studies. The diagnosis of osteoporosis was determined from lateral calcaneus and spine radiographs. Postmenopausal osteoporotic female subjects had significantly lower BUA values than normal women (P less than 0.001). There was a significant negative linear relationship between BUA and age in the postmenopausal subjects. No correlation was found between body size parameters (weight, height, and body mass index) and ultrasound attenuation. These results indicate that BUA may be a useful technique for detection of persons at risk. PMID- 1422960 TI - Menopausal bone loss is partially regulated by dietary intake of vitamin D. AB - Five years ago we reported results from a cross-sectional study of the effect of nutritional factors on calcium-regulating hormones and bone loss in perimenopausal women. We found an inverse correlation between serum 25 hydroxyvitamin D (25OHD) and immunoreactive parathyroid hormone (PTH), and we postulated that over time, women with lower 25OHD would lose more bone because of increased bone remodeling induced by secondary hyperparathyroidism. We have followed 38 of these women for 5 years. Twenty-two have gone through menopause and we are reporting observations on these 22 subjects. Bone mineral analysis was performed twice a year at the distal and mid-radius using single-photon absorptiometry. The slope of the bone mineral content curve was calculated by least squares. Bone loss increased within 6 months of the rise in serum follicle stimulating hormone (FSH) to greater than 40 mIU/ml. We continued to see a negative correlation between 25OHD and PTH (r = -0.450, P = 0.03). Premenopause, PTH was negatively correlated with the proximal bone mineral content (PBMC) slope (-0.604, P = 0.002). The distal bone mineral content (DBMC) 5-year slope was correlated with dietary vitamin D (r = 0.509, P = 0.02), the higher the intake, the less negative the slope. The 5-year PBMC slope was negatively correlated with serum osteocalcin (OC) levels (r = -0.382, P = 0.08). Before menopause, the change in PBMC was positively correlated with OC (r = 0.450, P = 0.03). Postmenopause, the correlation with DBMC slope was negative (r = -0.506, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422962 TI - Rectal salmon calcitonin for the treatment of postmenopausal osteoporosis. AB - In a 2-year study, we examined bone mass and calcium metabolism in 36 elderly women with moderate osteoporosis. The study period comprised 1 year of observation, during which the women received no treatment affecting calcium metabolism, and 1 year of treatment, during which all participants received daily salmon calcitonin (sCT) 100 IU rectally and calcium 500 mg. During the observational period a significant bone loss of 1.5% was seen in the forearm (P less than 0.01), whereas the spinal bone mass was virtually unchanged. After institution of treatment, the bone loss was arrested in the forearm and a significant increase of about 2% was seen in the spine (P less than 0.01). The net effect of treatment revealed a positive outcome in both bone compartments (1.9% and 2.9%, P less than 0.05-0.01). Correspondingly, the parameters of bone turnover (serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxy-proline/creatinine) did not change during the observational period, but significantly declined, 10-30%, during sCT treatment (P less than 0.01-0.001). Tolerance was generally good, although in one woman, anoscopy revealed irritative changes in the rectal mucosa. We conclude that, given rectally, sCT is well absorbed and well tolerated and that it has a beneficial effect on calcium metabolism in moderately osteoporotic women. PMID- 1422963 TI - Bone tissue response to four-month antiorthostatic bedrest: a bone histomorphometric study. AB - A histomorphometric analysis were made on iliac crest biopsies from eight healthy male volunteers submitted to a 4-month antiorthostatic bedrest. Bone mass and bone cell parameters, reflecting resorption and formation activities, were measured before and after the bedrest period. Trabecular bone volume and mean cortical thickness were not modified despite a decreased number of trabeculae and nonsignificant increase of the trabecular thickness; total and active resorption surfaces and the number of osteoclast per mm2 of trabecular surfaces do not vary significantly. Osteoid thickness does not vary but we found a reduced osteoid surface and a nonsignificant decreased osteoid volume. Our results suggest that bone architecture may be more affected by the reduction of mechanical forces than the bone mass. These modifications were supposed to be the result of an accelerated bone turnover in the early stage of immobilization. In this study, we failed to find disuse osteoporosis; however, we must point out that the new organization of the trabeculae could affect the bone mechanical properties. PMID- 1422964 TI - Hemopoietic functions of marrow-derived osteogenic cells. AB - Osteoblasts, members of the marrow stromal cellular network, may play an active role in the hemopoietic microenvironment as well as in bone remodeling. In this study, we examined the extent to which marrow-derived osteogenic cells (MBA-15) possess various stromal functions. This marrow stromal-derived cell line was shown by us to exhibit osteoblastic characteristics in culture and to form bone in vivo. These cells are shown here to constitutively produce and secrete cytokines identified as M-CSF, GM-CSF, and IL-6. MBA-15 cells modulate growth of normal and malignant myeloid and lymphoid cells as well as leukemia cell lines in vitro. Cell-cell interactions were studied in co-cultures with adherent MBA-15 cells and the target hemopoietic cells. Growth inhibition effects, observed under various experimental conditions, can be attributed to the presence of different soluble and membrane-bound inhibitory activities produced by MBA-15 cells. Thus, MBA-15 cells spontaneously produce both stimulators and inhibitors that can affect myeloid and lymphoid cell growth. Marrow osteogenic cells may therefore participate in the stromal regulation of hemopoiesis. PMID- 1422965 TI - The localization and characterization of proteinases for the initial cleavage of porcine amelogenin. AB - In the outermost layer of porcine-developing enamel adjacent to the ameloblasts in the secretory stage, the activities of two proteinases having molecular masses of 76 and 78kDa were detected by enzymography using gelatin as a substrate. On the other hand, high activities of known 30 and 34kDa proteinases were localized in the inner layer of the enamel. The 76kDa proteinase cleaved the carboxyl terminal peptide of porcine 25kDa amelogenin to convert it to 20kDa amelogenin. The 78kDa proteinase also acted on the 25kDa amelogenin similarly, but its activity was weak. The results indicate that the 25kDa amelogenin synthesized and secreted by ameloblasts is converted to 20kDa amelogenin by the action of proteinase localized in the outermost layer of the secretory enamel, and then further degraded by the proteinases in the inner layer of the enamel associated with the increase of mineralization. PMID- 1422966 TI - The anabolic effect of estrogen on endosteal bone formation in the mouse is attenuated by ovariohysterectomy: a role for the uterus in the skeletal response to estrogen? AB - In the mouse, the anabolic effect of estrogen on the uterus and its stimulatory effect on endosteal bone formation are well documented. When these observations are coupled with the recent description of uterine-derived bone cell mitogens, it raises the possibility that uterine hypertrophy in response to estrogen might lead to the production and release of factors that participate in the skeleton's anabolic response to estrogen. To determine if the stimulatory effects of estrogen on endosteal bone formation and uterine tissue in the mouse are related, we have studied this specific skeletal response to ovariectomy (OVX) and ovariohysterectomy (OHTX), and to two levels of 17 beta-estradiol (17 beta-E2). To assess treatment effects, 48 Swiss-webster mice were assigned to six groups: OHTX/oil vehicle, OVX/oil vehicle, OHTX/150 micrograms 17 beta-E2, OHTX/300 micrograms 17 beta-E2, OVX/150 micrograms 17 beta-E2, and OVX/300 micrograms 17 beta-E2. Animals were treated once per week with vehicle or the respective 17 beta-E2 dose. To quantitate bone formation, fluorochrome labels were administered at the beginning and end of the experimental period. At the conclusion of the 5 week study, tibiae were processed undecalcified for embedding in methyl methacrylate plastic. Cross-sectional areal properties and bone formation rates were quantitated from 30 microns mid-diaphyseal sections using a Bioquant Bone Morphometry system. Compared with the vehicle-treated OVX and OHTX mice, 150 micrograms of 17 beta-E2 administered once per week significantly increased cortical bone areas (P less than 0.05) but cortical bone widths and the ratio of cortical bone area to total bone area was increased only in estrogen-treated OVX mice (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422967 TI - Experimental changes in mineral content of juvenile mouse femora. AB - Juvenile laboratory mice were exposed to hypergravity (8 g), burrowing exercise, swimming to exhaustion, an anabolic steroid, and swimming and an anabolic steroid for 30 days to determine the variability of skeletal mineralization during growth. Changes in mineralization were correlated with changes in bending strength. Experimental mouse femora were loaded to failure in a cantilever beam configuration to determine bending strength, and ashed to determine total mineral content. Between experimental groups, mineral content ranged from 66.0 to 71.2% with the greatest change from the control being a 4.7% decrease in mineralization in the male swimming exercise group (P less than 0.001). Within two age-matched experiments, the first showed that the group with the greatest decrease in mineralization also had the greatest reduction in bending strength (P less than 0.001). The second age-matched experiment showed that the group with the greatest reduction in mineralization had bending strength greatly reduced (P less than 0.001). However, in this experiment, the weakest femora were in the anabolic steroid group that did not have the mineral content reduced. We conclude that (1) mineralization of juvenile mouse femora is extremely variable given varied conditions of exercise or loading; (2) mineralization of normal bone is decreased more often and to a greater extent than increased from normal exercise controls; (3) the decrease in mineralization seen here can decrease bending strength; and (4) the decrease in mineralization seen was not caused by a decrease in a mechanical loading but was probably due to a corticosterone-mediated psychological stress response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422968 TI - Sex differences in the acquisition of total bone mineral mass peak assessed through dual-energy X-ray absorptiometry. AB - Dual energy X-ray absorptiometry evaluation of total body bone mineral content (TBBM), total bone mineral density (TBMD), and regional bone mineral content (BMC) (head, trunk, arms, and legs) was carried out in order to assess sex differences of bone in 120 women and 121 men aged 15-29 years. Subjects from both sexes were divided into 5-year groups (15 through 19, 20 through 24, and 25 through 29 years old, respectively). Significantly higher values for TBBM, TBMD, and regional BMC were observed in males compared with females in the 20 to 24 and 25 to 29-year-old groups (P less than 0.001), but not in the group aged 15-19. After adjusting TBBM for lean body mass (LBM), we observed significantly lower values of TBBM/LBM in the males compared with females in all the age groups. A positive and significant correlation was observed between TBBM and age in the males of all the groups (r = 0.624, P less than 0.001), but not in the females. These data suggest that total bone mass peak acquisition takes place earlier in women than in men, leading to more reduced bone mass value, which in turn may be an osteoporosis predisposing factor. PMID- 1422969 TI - Reproducibility of lateral spine scans using dual energy X-ray absorptiometry. AB - Reproducibility of lateral spine dual energy X-ray absorptiometry (LAT DEXA) scans using a Lunar DPX-L scanner was assessed in a cadaveric phantom and in patients. One hundred phantom measurements over 7 months demonstrated a longitudinal stability of 1.7% (coefficient of variation, CV). Additional scans were performed with the phantom rotated by up to 20 degrees in each of the three orthogonal planes to assess the effects of variable patient positioning. Horizontal and vertical rotation of the spine had little effect on the estimated bone mineral density (BMD), however, axial rotation of greater than 8 degrees led to errors in the BMD measurement. One hundred consecutive patients had two lateral scans performed within 1 month. BMD (range 0.10-1.6 g/cm2) was determined for each scan by one operator. Significant overlap from ribs and pelvis was often seen with L2 and L4 vertebrae but one vertebra (L3) could be measured in every case. Intraoperator and interoperator variability was assessed by three experienced operators, each analyzing 10 patients' scans on five separate occasions, and was found to be less than 1.1% for a single vertebra. BMD estimation of vertebral bodies and midslices by lateral DEXA scans (CV% of 3.8% and 4.6%) have a 95% confidence interval of 0.074 g/cm2 and 0.096 g/cm2, respectively for two vertebrae. This variability is due mainly to axial rotation, with operator variability, horizontal rotation, and vertical rotation having little effect on BMD estimation. PMID- 1422970 TI - Human amelogenesis. I: High resolution electron microscopy study of ribbon-like crystals. AB - Ribbon-like crystals, from developing enamel of human fetuses, were studied by high resolution electron microscopy. These crystals were classically described as the first organized mineral formed during amelogenesis. They were characterized by a mean width-to-thickness ratio (W.T-1) of 9.5, and 40% were bent. On lattice images we noted the presence of the central dark line (CDL) associated with white spots. Both structures were found in crystals with a minimum thickness of 8-10 nm. CDLs were localized in the center of the crystals and seemed to be linked to the initial growth process, but their exact structure and function were not fully determined. We were able to study the structure of the ribbon-like crystals with a Scherzer resolution close to 0.2 nm. The good correspondence between experimental and computed images showed that their structure was related to hydroxyapatite (HA). In addition, the presence of ionic substitutions and deficiencies were also compatible with HA. In this study, about 50% of the crystals showed structural defects. Screw dislocations were the most often noted defects and were observed within crystals aligned along five different zone axes. Low- and high-angle boundaries were also detected. Low-angle boundaries, found in the center of the crystals, could thus be related to CDLs and be implicated in the nucleation step of crystal formation, whereas high-angle boundaries could result from the fusion of ribbon-like crystals. Such mechanisms could induce an acceleration of the growth in thickness of the crystal observed during the maturation stage of amelogenesis. PMID- 1422971 TI - Alterations of the mineralization profile and osteocalcin concentrations in osteoarthritic cortical iliac crest bone. AB - The relation between bone mineralization and osteocalcin content was investigated in iliac crest cortical bone obtained at necropsy in young females and in two groups of elderly women with and without osteoarthritis of the hands evaluated by X-ray. Using density fractionation technique, the bone was separated into fractions of increasing density from 1.72 to 2.30 g/ml. The mineralization profile revealed a significant shift to higher densities in the osteoarthritis cases compared with young adults (P less than 0.005) and age-sex-matched controls (P less than 0.001). The ash, calcium, and phosphorus content of the bone increased with increasing density of the fractions whereas collagen content, measured as hydroxyproline, decreased. The osteocalcin concentration of each fraction was determined in the supernatants obtained after EDTA-extraction in the presence of protease inhibitors. In the young control and osteoarthritis group, the osteocalcin content in the lowest density fractions was higher compared with the older non-osteoarthritic group. Osteocalcin content of the high density fractions, representing highly mineralized osteons, was the same in the three groups studied. These findings support the hypothesis that quality differences in bone may explain the inverse relationship between osteoarthritis and osteoporosis. PMID- 1422972 TI - Effects of a short course of oral phosphate treatment on serum parathyroid hormone(1-84) and biochemical markers of bone turnover: a dose-response study. AB - To investigate the possible use of oral phosphate as an activator of bone remodeling in coherence treatment of osteoporosis, 82 postmenopausal females, aged 50-75 years, were randomized to treatment with oral phosphate (750, 1500, or 2550 mg/day) or placebo for 7 days and followed for 4 months thereafter. All patients had sustained at least one previous fracture of the distal forearm and had a bone mineral content of the contralateral forearm or bone mineral density of the lumbar spine lower than normal mean for age. Urinary phosphate/creatinine ratio increased in a dose-dependent fashion during treatment (P less than 0.001), whereas no significant changes were seen in serum phosphate or serum calcium. Serum parathyroid hormone (PTH) rose significantly (P less than 0.05) during treatment to a maximum of 36 and 33% in the groups receiving 1500 and 2250 mg/day, respectively, whereas serum 1,25-dihydroxycholecalciferol remained unchanged. In the group receiving 1500 mg/day, mean serum osteocalcin was increased in the period from day 1 to day 28 (P less than 0.05), but no significant changes were observed in urinary hydroxyproline/creatinine ratio, or serum bone alkaline phosphatase. We conclude that a short course of oral phosphate treatment increases serum PTH considerably. Furthermore, 1500 mg/day but not 2250 mg/day increases serum osteocalcin. No clear biochemical evidence, however, of increased activation of bone remodeling could be demonstrated in either group. PMID- 1422973 TI - Successful treatment of low turnover osteoporosis resulting from prolonged reserpine therapy with intermittent calcitonin and phosphate therapy. AB - Coherence therapy, popularly known by the acronym ADFR (Activate, Depress, Free, Repeat), was designed to increase bone mass in osteopenic patients. Accordingly, we report a case of a hypogonadal male with histologically proven low bone turnover osteoporosis and a progressive vertebral fracture syndrome, who responded favorably to ADFR treatment with the use of salmon calcitonin and inorganic phosphate. Dramatic increments in bone mass were observed during a 68 month period of therapy. Serial quantitative computerized tomography demonstrated a 146% increase from baseline in bone mineral density for the first 30 months of treatment, and dual energy radiography yielded a 36.5% increase for the subsequent 31-68 months. Furthermore, no episode of fracture occurred since coherence therapy was initiated. PMID- 1422974 TI - Interactions between growth hormone and dexamethasone in skeletal growth and bone structure of the young mouse. AB - The present study investigated the interactions of growth hormone (GH) and glucocorticoid on skeletal growth and bone structure in young mice. The purpose of this study was to examine the possible prevention by GH of the damage inflicted by dexamethasone (Dex) at sites of skeletal growth and ossification. Dex (1 mg/kg) with or without rat GH (rGH) or bovine GH (bGH), 1 mg/kg, was given for 4 weeks, from age 3-7 weeks, to female ICR mice. Tibiae, humerus, and vertebrae were analyzed morphometrically and biochemically. Growth, as determined by the mouse weight, tibial length, and humerus protein content was found to be compromised by dexamethasone. This was prevented by rGH or bGH. The epiphyseal growth plate width, trabecular bone volume, cortical bone width, mineral bone content, and alkaline and acid phosphatase activity were decreased by dexamethasone. These were prevented by rGH or by bGH. The findings of the present study suggest that in the mouse, GH can decrease or even avoid some of the pathological features in growing bones inflicted by high-dose glucocorticoid treatment. PMID- 1422975 TI - Mechanism of action of beta-glycerophosphate on bone cell mineralization. AB - Experiments were performed to determine whether beta-glycerophosphate (beta-GP) promoted mineralization in vitro by modulating bone cell metabolic activity and/or serving as a local source of inorganic phosphate ions (Pi). Using MC3T3 E1, ROS 17/2.8, and chick osteoblast-like cells in the presence of beta-GP or Pi, we examined mineral formation, lactate generation, alkaline phosphatase (AP) activity, and protein and phospholipid synthesis. Neither beta-GP nor Pi modulated any of the major biosynthetic activities of the bone cells. Thus, we found no change in the levels of phospholipids, and the total protein concentration remained constant. Measurement of lactate synthesis showed that beta-GP did not effect the rate of anaerobic glycolysis. Evaluation of medium Pi levels clearly indicated that beta-GP was hydrolyzed by bone cells; within 24 hours, almost 80% of 10 mM beta-GP was hydrolyzed. It is likely that this local increase in medium Pi concentration promoted rapid mineral deposition. Chemical, energy dispersive X-ray, and Fourier transform infrared analysis of the mineral formed in the presence of beta-GP showed that it was nonapatitic; moreover, mineral particles were also seen in the culture medium itself. Experiments performed with a cell-free system indicated that mineral particles formed spontaneously in the presence of AP and beta-GP and were deposited into a collagen matrix. We conclude that medium supplementation with beta-GP or Pi should not exceed 2 mM. If this value is exceeded, then there will be nonphysiological mineral deposition in the bone cell culture. PMID- 1422976 TI - Avian osteoblast conditioned media stimulate bone resorption by targeting multinucleating osteoclast precursors. AB - Osteoblasts are thought to secrete factors that regulate the rate of osteoclastic bone resorption. We studied the effect of osteoblast conditioned medium on bone degradation by multinucleated osteoclast-like cells generated in vitro from mononuclear precursors and found that the medium stimulates bone degradation primarily through interactions with osteoclast precursors. The conditioned medium also stimulates expression of the osteoclast-specific antigen 121F. The increased bone degradation, but not increased 121F expression, is due to the conditioned medium maintaining activity of the osteoclast precursors. Although the osteoclast precursors exhibit the DNA fragmentation characteristic of apoptosis, the osteoblast conditioned medium does not prevent such fragmentation. Chicken macrophage growth factor neither mimics nor augments the ability of the conditioned medium to stimulate bone degradation. Studies of osteoclast generation or function should carefully consider whether the effects are dependent on the viability of the resorbing cells. PMID- 1422977 TI - Light and electron microscopic abnormalities in diastrophic dysplasia growth cartilage. AB - Light and electron microscopic studies of diastrophic dysplasia iliac crest growth cartilage performed on five occasions in two patients from 1 to 10 years of age reveal extensive cell and matrix abnormalities at each time period. Light microscopy shows atypical chondrocytes with extreme variation in size and shape, and premature cytoplasmic degeneration, and formation of target ghost cells. Prominent, densely staining fibrotic foci are present throughout the cartilage. Ultrastructure reveals some structurally intact chondrocytes with a single large fat inclusion, slightly dilated rough endoplasmic reticulum, and abundant glycogen. As early as 1 year of age cystic degeneration of chondrocyte cytoplasm is evident with indistinct organelles seen. The cartilage matrix demonstrates a general increase in fibrous tissue as well as the fibrotic foci. The collagen in these foci is remarkably abnormal. It is composed of short, extremely broad fibrils ranging from 150 to 950 nm in width which are separated at their terminal ends but fused to each other centrally in random fashion. On cross-section there are very few round fibrils but rather a marked irregularity in shape giving the appearance of having fibrils randomly added to others to form enlarged nonuniform fibril aggregates. On longitudinal sectioning, regular cross-banding across the entire fibril width is seen but fibril splitting and aggregation are highly irregular.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422978 TI - Effect of ipriflavone and estrogen on the differentiation and proliferation of osteogenic cells. AB - The effect of ipriflavone (IP) on the proliferation and differentiation of rat osteoblast-like (ROB) cells and human periodontal ligament fibroblasts (HPLF) was studied in the presence and absence of estrogen. ROB cells were isolated from newborn rat calvaria by sequential collagenase digestion and HPLF from the outgrowth of human periodontal ligament in culture. The alkaline phosphatase (ALP) activity, employed as a marker of bone cell differentiation, was significantly enhanced by IP in both cell types; however, the concentration at which IP had a maximal effect was lower in ROB cells than in HPLF (10(-10) versus 10(-7) M, respectively). Cell proliferation judged by DNA content was either constant (ROB cells) or slightly increased (HPLF) by IP up to 10(-10) M, and decreased significantly above that concentration. In addition, the dose-dependent effect of estrogen on the growth and differentiation of each cell type in the presence and absence of IP was also tested. At the concentrations of IP which showed maximum effects in the induction of ALP, 10(-10) M for ROB cells and 10( 7) M for HPLF, IP inhibited DNA increase in an estrogen-independent manner. Estradiol (10(-11)-10(-9) M) itself increased the growth rate of both cell types significantly in a dose-dependent manner. Regardless of the concentrations of estradiol tested, ALP activities of both ROB cells and HPLF were elevated by the addition of IP. The ratio of ALP in the presence and absence of IP was similar over the range of estradiol concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1422979 TI - Stimulatory effect of ipriflavone on formation of bone-like tissue in rat bone marrow stromal cell culture. AB - The effects of ipriflavone (IP) (10(-5) M) on bone formation were studied in stromal cells from the femoral bone marrow of young adult rats cultured for 21 days in the presence of beta-glycerophosphate and dexamethasone. Stereoscopic microscopy showed nodule formation after 14 days of culturing, and both the number and the size of the nodules increased with time. The alizarin-red-stained calcified area in the nodules in the IP group was nearly 4 times as large as that in the control after 21 days. Light and electron microscopy revealed the presence of many osteoblast-like cells with developed rough endoplasmic reticulum and Golgi apparatus in the nodules in the control group after 14 days, and a collagenous fibril network was seen among the cells. After 21 days, calcification of the dense collagenous fibril network and bone matrix-like tissue were observed in many nodules, resulting in the formation of bone-like tissue containing osteocyte-like cells. In the IP group, the collagenous fibril network area in the nodules was greater than that in the control after 14 days, and a further increase in both the dense collagenous fibril network area and calcified bone like tissue area was observed after 21 days. These findings indicate that IP stimulates bone-like tissue formation in the rat bone marrow stromal cell culture, suggesting that the promotion of collagen production by osteoblasts is involved in the stimulation of bone-like tissue formation by IP. PMID- 1422980 TI - Histochemical and fine structural study of bone of ipriflavone-treated rats. AB - Bone labeling, histochemical, and fine structural studies were performed in order to clarify the effects of ipriflavone (IP) on rat bone tissue in vivo and in vitro. Labeling experiments showed a slight increase in bone formation during 3 days' administration. It was also noted that many osteoclasts detached from the bone surface at 1, 2, and 6 hours after administration in vivo. In addition, irregular localization of tartrate-resistant acid phosphatase (TRACPase) activity was observed in osteoclasts. Fine structurally, IP-treated osteoclasts exhibited irregularity in their ruffled borders, as reported in calcitonin administration, and many enlarged rough endoplasmic reticuli and vacuoles were observed. However, osteoclasts at 12 hours after administration, as well as the control, indicated recovery features from the effect of IP. Osteoblast proliferation and differentiation led to increasing alkaline phosphatase activity (ALPase) with time as well as the development of rough endoplasmic reticuli and Golgi apparatus with well-developed fine structure. These findings imply active synthesis of bone matrix. In our in vitro experiment, osteoclasts and osteoblasts displayed histochemical and fine structural characteristics similar to those observed in our in vivo experiment. Moreover, fewer TRACP-positive mononuclear cells were observed after 24-hour culture with IP than with the control. These results suggest that IP inhibits directly and/or indirectly differentiation and activity of osteoclasts and also promotes differentiation of osteoblast-lineage cells and their bone-forming activity. PMID- 1422982 TI - Inhibitory effect of ipriflavone on pit formation in mouse unfractionated bone cells. AB - Effects of ipriflavone (7-isopropoxyisoflavone) on osteoclast-induced bone resorption were evaluated using an unfractionated bone cell culture system containing mature osteoclasts from the femur and tibia of newborn mice. When cells were cultured for 4 days on dentin slices in the presence of 5% fetal bovine serum and 10(-8) M 1 alpha, 25(OH)2D3, ipriflavone (3 x 10(-7) -3 x 10(-5) M) inhibited pit formation and caused a decrease in the number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs). The lowest significant effect was observed at a concentration of 10(-6) M. Unlike ipriflavone, calcitonin inhibited pit formation 4 days after the culture was started without affecting the number of TRAP-positive MNCs. Ipriflavone still inhibited pit formation when the culture period was 13 days, when new osteoclasts were expected to be formed. These findings suggest that ipriflavone inhibits new osteoclast formation and bone resorption at the cellular level. PMID- 1422981 TI - Effects of ipriflavone on calcitonin synthesis in C cells of the rat thyroid. AB - Ipriflavone is known to stimulate calcitonin (CT) secretion from the thyroid glands of female animals, but the exact mechanism of this action remains unknown. In the present study, an increase of CT production in thyroid C cells of female rats, but not of male rats, was proven immunohistochemically. Furthermore, the parallel increase of CT mRNA in those thyroid glands was confirmed by Northern blot analysis. These results proved that ipriflavone stimulates not only CT secretion but also CT synthesis in thyroid C cells and that the changes were gender dependent (greater in females). In order to investigate the effect of estrogen on the ipriflavone-induced increase of CT in female rat thyroid gland, CT and CT mRNA in the thyroid glands of untreated, ovariectomized, and estrone treated (postovariectomy) rats were examined by both immunohistochemistry and Northern blot technique. Serum levels of CT and calcium were also examined. Against expectation, estrone failed to produce any significant effect on the ability of ipriflavone to induce CT synthesis and secretion. PMID- 1422983 TI - Effect of ipriflavone on bone mineral density and calcium-related factors in elderly females. AB - The effects of ipriflavone (7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one) on bone mineral density (BMD) of the 3rd lumbar vertebra and on calcium (Ca)-related factors, including serum calcitonin (CT) levels before and after rapid calcium infusion (4 mg/kg for 5 minutes), were studied in 11 elderly female subjects (80 +/- 2 years of age, mean +/- SE). Ipriflavone (IP) administration (600 mg/day, 7 months) resulted in inhibition of BMD loss in 7 patients (responders, mean change of BMD value 2.2 +/- 2.3%), whereas 4 patients showed a loss of BMD (nonresponders, mean change of BMD value -13.1 +/- 2.6%) compared with pretreatment values. The responder group showed a significant increase in mean pretreatment serum CT levels (from 20 +/- 2 pg/ml to 42 +/- 7 pg/ml, P < 0.05) after treatment with IP, and a significant decrease in the mean basal serum level of corrected Ca (from 9.6 +/- 0.2 mg/dl to 8.7 +/- 0.1 mg/dl, P < 0.01) after treatment with IP; nonresponders did not show these changes. For responders, both the percentage of change and the maximal value of serum CT in response to Ca infusion were maintained at rather high levels, both before and after IP treatment; nonresponders showed almost no response to a stimulation test for CT. These findings suggest that IP inhibits bone loss in elderly female subjects possibly through the mechanism of increasing CT secretion. PMID- 1422984 TI - Ipriflavone inhibits murine osteoclast formation in vitro. AB - Ipriflavone, one of the isoflavone derivatives, is a therapeutic drug for osteoporosis. The mechanism is thought to be the inhibition of bone resorption. In the present paper, we report that ipriflavone inhibited formation of osteoclasts from murine spleen cells co-cultured with stromal cells cloned from murine bone marrow. In this system, ipriflavone inhibited osteoclast generation in a dose-dependent manner (10(-7)-10(-5) M). Ipriflavone also inhibited prostaglandin E2 production in MC3T3-E1 cells, which are widely employed as osteoblasts. Moreover, ipriflavone inhibited the proliferation of stromal cells (10(-6)-10(-5) M), but not osteoblastic cells. These results suggest that one mechanism for the inhibitory effects of ipriflavone on bone resorption is the inhibition of osteoclast formation through inhibiting prostaglandin E2 production in osteoblasts and thereby suppressing proliferation of stromal cells. PMID- 1422985 TI - High frequency of lipoprotein lipase deficiency in the Quebec population. PMID- 1422986 TI - Recycling and 'transplantation' of implantable electronic devices. PMID- 1422987 TI - Can we afford not to reuse cardiac pacemakers? PMID- 1422988 TI - Sex differences in the evolution of the electrocardiographic QT interval with age. AB - OBJECTIVE: To investigate sex differences in the evolution of the QT interval with age. SUBJECTS AND METHODS: A community-based representative North American population sample of 14,379 children and adults aged from birth to 75 years. The measured QT intervals (QTm) were determined by a computer algorithm and QTm, corrected for heart rate (HR), was expressed as QT index: QTI = (QTm/Tp) x 100, where QTp is the predicted QT from the formula QTp (ms) = 656/(1 + HR/100). MAIN RESULTS: The QTI values of females were significantly longer than of males in all age groups from 15 to 50 years tested at yearly intervals. This difference was due to a 20 ms drop in rate-corrected QT values in adolescent males after puberty, whereas QT values of females remained unchanged throughout the growth, maturation and reproductive years. The new QT prediction formula explained 83% of total QT variance in females and 82% in males after adjustment for heart rate and for the observed significant influence of ventricular excitation time (QRS duration) on QT interval in both sexes and a correction for QT age trend in males. CONCLUSIONS: The sex difference in the QT interval is due to QT shortening in males after puberty rather than QT prolongation in women during reproductive years. The fact that QRS duration is a significant determinant of the QT interval has important theoretical implications for attempts to model the ventricular repolarization process and it indicates that the traditional concept of reverse sequence of ventricular repolarization is not universally valid in all myocardial regions. PMID- 1422989 TI - The reuse of cardiac pacemakers. AB - OBJECTIVE: To provide decision makers with a synthesis of the relevant information concerning the safety of pacemaker reuse, the ethical and legal issues which it raises and the extent of financial savings which may result. DATA SOURCES: Medline data bank and the bibliographies of review articles in English concerning refurbishment and reuse of cardiac pacemakers published up to June 1991. DATA SYNTHESIS: Since 1978, reports of safe reuse of pacemakers have appeared in 11 countries. By 1984, review of nearly 2000 installations had produced no evidence of increased mortality or morbidity. The norms which must be respected to ensure safety are now well-known. The savings that might result from reuse can only be approximated. In Canada in 1989, 8684 pacemakers were installed. Assuming that 20% might be available for reuse, this practice might save approximately $4,000,000 per year to the Canadian health care system. CONCLUSIONS: Properly carried out, pacemakers can be reused at an acceptably low risk. Any institution contemplating pacemaker reuse should define and approve appropriate guidelines and protocols governing the process. A registry to document the reuse of pacemakers for the next few years is desirable. PMID- 1422990 TI - Directional coronary atherectomy at the Toronto and Mount Sinai Hospitals: report of the initial 120 procedures. AB - OBJECTIVE: To assess the procedural success and complication rates of the first 120 directional coronary atherectomy cases performed at two Toronto hospitals. DESIGN AND SETTING: Case series in tertiary referral centres. PATIENTS: One hundred and thirteen patients in whom 120 atherectomy procedures were attempted between July 1990 and April 1992. INTERVENTION: Directional coronary atherectomy. MAIN RESULTS: Angiographic success was obtained in 115 of 120 procedures (96%) involving 117 of 123 lesions (95%). Procedural success (angiographic success without death, myocardial infarction or coronary bypass surgery) was obtained in 110 of 120 procedures (92%). Adjunctive balloon angioplasty was required in 20 procedures (17%). There was one death at 36 h in an elderly patient who underwent an emergency procedure while in cardiogenic shock. Periprocedural non-Q wave myocardial infarction occurred in five patients. There were no Q wave myocardial infarctions. Three patients required coronary bypass surgery prior to discharge and vascular complications occurred in five patients. CONCLUSIONS: Directional coronary atherectomy can be performed with procedural success and complication rates comparable to conventional balloon angioplasty. Randomized trials are underway to determine if atherectomy results in a lower restenosis rate. PMID- 1422991 TI - Reverse redistribution on exercise thallium scintigraphy: relationship to coronary patency and ventricular function after myocardial infarction. AB - OBJECTIVE: To define prevalence, pathophysiology and relation to thrombolytic therapy of reverse redistribution (appearance of a new, or worsening of an existing, scintigraphic defect on 4 h delayed images compared with the stress thallium image). DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral centre. PATIENTS: Sixty-three patients with acute myocardial infarction. INTERVENTIONS: Tomographic exercise thallium scintigraphy, radionuclide angiography, and quantitative coronary angiography. MAIN RESULTS: Tomographic exercise thallium scintigraphy performed at day 10 revealed fixed defects in 15 patients, reversible defects in 22 patients and reverse redistribution in 26 patients; no difference in treatment assignment (tissue plasminogen activator versus placebo) was found among the three groups. Left ventricular function was similar in patients with fixed or reversible defects and reverse redistribution; global ejection fraction was 48 +/- 14, 51 +/- 10 and 48 +/- 5%, respectively, and regional infarct ejection fraction was 36 +/- 15, 40 +/ 13 and 37 +/- 18%, respectively. However, nitroglycerin administration resulted in a significantly greater improvement in regional ejection fraction in reverse redistribution patients (5 +/- 4%) than that in patients with fixed defect (2 +/- 5%, P < 0.05) or reversible defects (3 +/- 5%, P < 0.05). The infarct-related artery had a greater cross-sectional area in reverse redistribution patients (1.5 +/- 1.42 mm2) compared with those with reversible defects (0.50 +/- 0.26 mm2, P < 0.05), but was similar to fixed defect patients (1.04 +/- 0.88). CONCLUSIONS: Reverse redistribution on tomographic thallium scintigraphy is a frequent phenomenon (occurring in 40% of patients following acute myocardial infarction) and is independent of thrombolytic therapy. Patients with reverse redistribution have a more widely patent infarct-related artery and similar ventricular function, but significantly greater functional improvement following nitroglycerin administration compared with those with reversible or fixed defects. These data suggest myocardial salvage within the infarct zone in some patients with reverse redistribution. PMID- 1422992 TI - Effect of atropine and isoproterenol on tachycardia induction in asymptomatic patients with Wolff-Parkinson-White electrocardiographic pattern. AB - OBJECTIVE: To determine if pharmacological interventions aimed at altering autonomic tone would allow induction of orthodromic atrioventricular reentrant tachycardia in asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. DESIGN: Prospective interventional protocol in consecutive eligible patients. SETTINGS: University hospital. PATIENTS: Eighteen asymptomatic patients (13 male and five female) with the Wolff-Parkinson-White electrocardiographic pattern without inducible tachycardia in the drug-free state. INTERVENTION: Electrophysiological assessment was performed at baseline, after intravenous administration of atropine (0.03 mg/kg) and during isoproterenol infusion (0.5 to 2 micrograms/min). RESULTS: Orthodromic reciprocating tachycardia was not inducible at baseline because of absent retrograde accessory pathway conduction in seven patients. In five patients, orthodromic atrial echo beats could be induced (which blocked retrogradely in the accessory pathway in three patients and anterogradely in the atrioventricular node in two). In the remaining six patients, neither orthodromic echo beats nor reciprocating tachycardia could be induced despite intact retrograde accessory pathway conduction. Following atropine administration (mean dose 1.9 +/- 0.3 mg), anterograde and retrograde accessory pathway effective refractory periods decreased from 360 +/- 172 to 284 +/- 62 ms and from 340 +/- 38 to 296 +/- 32 ms, respectively (both P < 0.05 versus control). Orthodromic reciprocating tachycardia was induced in two patients (nonsustained in one). During isoproterenol infusion (mean dose 1.0 +/- 0.3 micrograms/min), anterograde and retrograde accessory pathway effective refractory periods decreased further to 243 +/- 23 and 248 +/- 22 ms, respectively (both P < 0.05 versus after atropine); two further patients had inducible orthodromic reciprocating tachycardia (nonsustained in one). No patient with absent retrograde accessory pathway conduction developed retrograde accessory pathway conduction or reciprocating tachycardia with isoproterenol and/or atropine. CONCLUSIONS: Isoproterenol and/or atropine allowed tachycardia induction in four of 18 asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. In the majority of these patients, tachycardia is not inducible because of deficient retrograde accessory pathway conduction which does not improve with autonomic facilitation. PMID- 1422993 TI - Left main coronary artery dissection during cardiac catheterization. AB - A 70-year-old man with a downward sloping origin of the left main coronary artery developed left main dissection at coronary angiography and died despite emergency coronary by-pass surgery. Autopsy showed that the left main coronary artery had an acute angle take off and dissection had originated at the junction of the superior wall of the left main and the aorta. The combination of left main stenosis secondary to dissection and severe right coronary atherosclerosis had caused circumferential subendocardial left ventricular infarction. The left main coronary artery had mild atherosclerosis and lacked cystic medial necrosis. An angulated left main coronary artery may be a risk factor for dissection at angiography. PMID- 1422994 TI - Mycobacterium avium-intracellulare endocarditis causing rupture: replacement and repair with aortic homograft. AB - Aortic valve endocarditis with extension to the tricuspid annulus and ventricular septum in an intravenous drug abuser - with Mycobacterium avium-intracellulare identified as the offending organism - forms the basis of this report. The aortic root and ventricular septal defect were successfully repaired using an aortic cryopreserved homograft. This case is of particular interest because M avium intracellulare has not been recognized as a cause of endocarditis. The incidence of atypical organisms as a cause of endocarditis may increase in the future because of the rise of drug abuse and the acquired immune deficiency syndrome in North America. PMID- 1422995 TI - Anterior wall myocardial infarction in a 15-year-old diabetic female associated with spontaneously resolving coronary thrombosis. AB - Myocardial infarction is an uncommon event in childhood and adolescence, and only rarely is found to be due to atherosclerotic disease. This report describes a 15 year-old diabetic female with an acute anterior wall myocardial infarction in whom initial coronary angiography showed a thrombus of the proximal anterior descending coronary artery which had resolved spontaneously by the time a follow up study was carried out six weeks later. None of the usual precipitating causes of myocardial infarction in childhood were found, and repeat angiography did not demonstrate any fixed coronary artery disease. The relevant literature is reviewed and it is speculated that endothelial dysfunction, coronary spasm and altered coagulability may have contributed to the formation of intraluminal thrombus and subsequent infarction in this patient. PMID- 1422996 TI - Use of transtelephonic electrocardiographic monitoring in children with suspected arrhythmias. AB - Arrhythmias in children can produce various symptoms and their assessment often is difficult with usual methods. Transtelephonic electrocardiographic monitoring was used in 136 symptomatic patients (palpitations [112], syncope [six], chest pain [18]) for a mean duration of 86 +/- 65 days; mean age was 11.1 +/- 4.8 years and 62% were female. Of 398 recordings sent (mean 2.9 per patient) 32 revealed significant arrhythmias (8%). Of the 67 patients reporting symptoms during the recording period, only 24 had documented arrhythmias - 23 supraventricular tachycardia and one junctional tachycardia. The negative predictive value is 100%, compared with a low positive predictive value of 36%; sensitivity and specificity are, respectively, 100 and 62%. Of the 24 patients with documented arrhythmias, 54% were treated versus 13% of those with normal recordings (P < 0.01). At the end of the follow-up (mean duration 1.6 +/- 1.2 years), 63% of the patients with negative recordings had not complained of further symptoms versus 22% of those with documented arrhythmias (P = 0.001). Transtelephonic electrocardiographic monitoring is an important tool for documenting infrequent arrhythmias in children and even more for reassuring the patient and his or her family in the absence of significant arrhythmias. PMID- 1422997 TI - Time course of myocardial bloodflow changes during healing of myocardial infarct in pigs. AB - OBJECTIVE: To define the time course of changes in bloodflow and microsphere content at intervals between one and 28 days after surgical ligation of the circumflex coronary artery. SUBJECTS AND METHODS: After the ligation, pigs were assigned to six groups; all pigs in a group were reanesthetized at either one, three, seven, 14, 21 or 28 days post ligation to determine myocardial bloodflow distribution using radionuclide-labelled (15 +/- 2 microns) microspheres. RESULTS: Bloodflow to the infarct zone, 10 mins post ligation, was 7.3 +/- 1.4% of the normal flow. At one and three days post occlusion, infarct bloodflow was about 50% of the 'normal', declining after day 7 to between 20 and 25%. Bloodflow in the noninfarct zone was significantly elevated during the initial 14 days, declining thereafter to within the normal range. Microspheres in the infarct zone injected prior to the occlusion became concentrated and were diluted in the noninfarct zone; the ratio of infarct:noninfarct microsphere content rose progressively, reaching a 2.5-fold rise by day 28. CONCLUSIONS: The initial stages of infarct healing are associated with a marked rise in bloodflow with a subsequent fall. A more prolonged augmentation of flow is evident in the noninfarct zone. Microspheres are useful in estimating the relative magnitude of changes in the myocardium accompanying the healing (shrinkage) of the infarct and hypertrophy occurring in the noninfarct zone after a coronary occlusion. PMID- 1422998 TI - Intraoperative transesophageal echocardiographic demonstration of mitral leaflet tear following resection of a subaortic membrane. AB - A patient developed a tear of the anterior mitral leaflet following surgical resection of a stenotic subaortic membrane. This complication was diagnosed by intraoperative transesophageal echocardiography leading to successful repair of the mitral leaflet tear. PMID- 1422999 TI - Successful treatment of severe heart failure caused by idiopathic giant cell myocarditis. AB - A 53-year-old woman presented with increasing dyspnea over one month and signs of severe heart failure. A right ventricular biopsy revealed giant cell myocarditis. She was treated with a combination of cyclosporine, imuran and prednisone and improved dramatically--left ventricular ejection fraction increased from 13 to 66%. That such a response is possible has important implications with respect to both the etiology and treatment of this rare disorder. PMID- 1423000 TI - Thrombolytic therapy for right heart lesions. AB - Thrombolytic agents are accepted therapy for occlusion of coronary and peripheral arteries as well as for venous thromboses. Although the treatment of left heart prosthetic valve thrombosis has been evaluated, there are limited data showing the benefit of thrombolysis of right heart clots. Two patients with past histories of multiple cardiac operations were given fibrinolytic therapy for thrombosis involving right heart structures. The first patient had thrombosis of a prosthetic pulmonary valve. The second patient was a type IB tricuspid atresia who developed a Fontan duct stenosis and right atrial clot. Thrombolytic therapy may provide a safe alternative to surgical intervention for thrombosis of right heart structures and, even when incompletely effective, may provide additional time to prepare patients for surgical correction and possible protection against distal embolization during surgical intervention. PMID- 1423001 TI - Kallmann's syndrome and dilated cardiomyopathy. AB - A 52-year-old male previously known to have Kallmann's syndrome was admitted with congestive cardiac failure. He was found to have a dilated cardiomyopathy and died despite medical therapy. This report is the first known case of Kallmann's syndrome and dilated cardiomyopathy. PMID- 1423002 TI - Patients with symptomatic ischemia have larger thallium perfusion abnormalities and more adverse prognosis than patients with silent ischemia. AB - OBJECTIVE: To evaluate the mechanism for silent ischemia and the effect on prognosis. DESIGN: To test the hypothesis that patients with silent (compared with symptomatic) ischemia have less severe ischemia and a more favorable prognosis, the authors prospectively evaluated 152 consecutive patients with a positive exercise electrocardiogram with exercise thallium scintigraphy and followed them for two years. SETTING: Tertiary care university-based hospital. RESULTS: Asymptomatic patients during the exercise test had a greater exercise duration (9.4 +/- 3.1 versus 6.3 +/- 2.5 mins, P < 0.01), maximal heart rate (155 +/- 20 versus 136 +/- 20 beats/min, P < 0.01), systolic blood pressure (184 +/- 21 versus 176 +/- 23 mmHg, P < 0.05) and double product than patients who were symptomatic with chest pain. Although there was no difference in the magnitude of ST depression, time to ST depression was greater in the asymptomatic (5.6 +/- 2.7 mins), compared with symptomatic (4.6 +/- 2.6 mins), group (P < 0.01). Thallium ischemic score was smaller during asymptomatic ischemia (2.1 +/- 2.7) compared with symptomatic ischemia (3.9 +/- 3.1, P < 0.01). These findings were also demonstrated in a subgroup of 107 patients with both a positive exercise electrocardiogram and positive thallium scan. The patients with asymptomatic ischemia had a two-year cardiac event rate of 5.1% compared with 13.8% in the symptomatic patients (P = 0.065). CONCLUSIONS: Patients with asymptomatic ischemia have less severe myocardial ischemia and a better prognosis than patients with symptomatic myocardial ischemia during exercise testing. PMID- 1423003 TI - In vivo skeletal muscle metabolism during dynamic exercise and recovery: assessment by nuclear magnetic resonance spectroscopy. AB - BACKGROUND: The purpose of this study was to define temporally phosphorus metabolism and pH in the gastrocnemius muscles of 21 normal adult subjects during rest, dynamic exercise to exhaustion, and early and late recovery. METHODS: In vivo nuclear magnetic resonance spectroscopy. RESULTS: At rest, the ratio of phosphocreatine to the alpha peak of ATP averaged 2.26 +/- 0.25, the inorganic phosphate to ATP ratio averaged 0.31 +/- 0.08 and pH averaged 7.10 +/- 0.04. The phosphorus metabolites exhibited immediate and progressive changes with exercise, reaching their minimum (phosphocreatine, 0.95 +/- 0.41) or maximum (inorganic phosphate, 1.95 +/- 0.75) values at exhaustion, after an average exercise of 11 +/- 4 mins. In contrast, pH changed slowly during early exercise, but fell abruptly thereafter and averaged 6.76 +/- 0.17 at exhaustion. Phosphocreatine and inorganic phosphate began to return rapidly towards preexercise values immediately on cessation of exercise. However, pH declined further in the period immediately following cessation of exercise, reaching a nadir of 6.56 +/- 0.24 an average of 2 mins into recovery. Exercise duration did not correlate highly with any metabolic variable. CONCLUSIONS: The data support the concept that the metabolic physiology underlying physical exhaustion of dynamic exercising muscle is multifactorial. The post exercise drop in pH also suggests that normal subjects have a greater contribution to high energy phosphate production from glycolysis, as opposed to oxidative metabolism, in early recovery. PMID- 1423004 TI - Comparison of Doppler echocardiography and cardiac catheterization in patients requiring valve surgery: search for a 'gold standard'. AB - OBJECTIVE: To compare the sensitivities of Doppler echocardiography and cardiac catheterization in the diagnosis of severe valvular heart disease in patients requiring valve surgery. DESIGN: Retrospective analysis of Doppler echocardiograms and cardiac catheterizations. SETTING: Tertiary referral cardiovascular centre in a university setting. PATIENTS: Sixty-nine patients undergoing valve surgery between July 1988 and July 1990. RESULTS: The sensitivities of echocardiography and cardiac catheterization were 84 and 87%, respectively (P = 1.0) in 32 patients who underwent aortic valve surgery primarily for severe aortic stenosis; 83 and 67%, respectively (P = 1.0) in six patients with severe aortic regurgitation, and 100 and 85%, respectively (P = 1.0) in seven patients with combined severe aortic stenosis and regurgitation. The sensitivities of echocardiography and cardiac catheterization in 11 patients who underwent mitral valve surgery for severe mitral stenosis were 73 and 91%, respectively (P = 0.6) and 69 and 92%, respectively (P = 0.3) in 13 patients with severe mitral regurgitation. Sensitivities of echocardiography and cardiac catheterization in the diagnosis of severe tricuspid regurgitation in five patients who had tricuspid valve repair were 100 and 80%, respectively (P = 1.0). Two patients with severe aortic stenosis by echocardiography, but not by catheterization, did not undergo aortic valve replacement during valvular surgery; both required aortic valve replacement within two years of initial surgery because of heart failure. Four patients with severe tricuspid regurgitation identified by echocardiography did not have tricuspid repair; three had pulmonary hypertension and these patients had resolution of tricuspid regurgitation on follow-up. One patient with severe tricuspid regurgitation and absence of pulmonary hypertension required reoperation for tricuspid valve repair 10 months after initial operation. CONCLUSIONS: The sensitivity of echocardiography and cardiac catheterization in the detection of severe valvular lesions requiring surgery is similar. Discordant results should be reviewed carefully with knowledge of the inherent pitfalls of both techniques in order to ensure optimal patient outcome. PMID- 1423005 TI - HMG-CoA reductase inhibitors: a look back and a look ahead. AB - OBJECTIVES: This review is a follow-up to the Vancouver Symposium on hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors held in May 1990 (Can J Cardiol 1992;8 [Supplement A]: March 1992). The aim is to provide an update on the issues discussed at the time, focusing primarily on aspects of practical importance for the clinician and new developments. DATA SOURCES: The available literature on HMG-CoA reductase inhibitors from May 1990 to May 1991 was systematically reviewed. DATA SELECTION: The review focuses especially on human studies which provide a better understanding of mechanisms of action, pharmacokinetics, efficacy, safety and tolerance, as well as structure-function relationships. CONCLUSIONS: A look back indicates that HMG-CoA reductase inhibitors, as a class, appear to be safe and effective for long term use and constitute a major drug addition for the control of hypercholesterolemia. Combination therapy may enhance effectiveness but close monitoring is needed when used in conjunction with fibrates and nicotinic acid because of potential muscle toxicity. A look ahead uncovers new properties that may be of potential benefit in the treatment of atherosclerosis, hypertension, cholelithiasis, mild renal disease and possibly thrombogenesis and cancer. In view of the fact that the magnitude of low density lipoprotein cholesterol lowering is commensurate with the degree of atherosclerosis regression, HMG-CoA reductase inhibitors provide a unique tool for the control of aggressive atherosclerotic vascular disease and for secondary prevention of coronary artery disease. PMID- 1423006 TI - Reset of the osmotic threshold for vasopressin in rats fed a low NaCl, K-free diet. AB - Activation of the renin-angiotensin system induced by feeding a low NaCl, K-free (LS) diet is associated with polydipsia and a chronic reduction in effective plasma osmolality (efPosm). We have recently shown that converting enzyme inhibition with enalapril (EP) abolishes polydipsia. The present study was designed to test the hypothesis that the osmotic threshold for vasopressin is reset in rats fed the LS diet and to examine the effect of EP on ambient and osmotically stimulated plasma vasopressin levels (PAVP). Animals were fed the LS diet or a control salt diet and treated with vehicle or the lowest dose of EP sufficient to prevent polydipsia (7.5 mg.kg-1.day-1) in rats fed the LS diet. PAVP and efPosm were measured under ambient conditions and after osmotic loading. Urine osmolality (Uosm) was measured under ambient conditions and after water loading. The chronic reduction in efPosm in LS rats was associated with the excretion of a Uosm 1-2 times greater than the corresponding Posm, PAVP similar to controls (LS, 2.27 +/- 1.08 vs. control, 1.19 +/- 0.22 pg/mL) and the ability to excrete a water load. Following osmotic loading, efPosm and PAVP increased significantly and similarly in both LS and control rats. EP administration had no effect on water intake, ambient efPosm and PAVP, and the AVP response to osmotic loading in rats fed the control diet. EP prevented polydipsia in LS rats, however it had no significant effect on ambient or osmotically stimulated PAVP or efPosm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423007 TI - Normal blood flow but lower oxygen tension in diabetes of young rats: microenvironment and the influence of sympathectomy. AB - Studies of rats with experimental streptozotocin (STZ)-induced diabetes at 4 months have identified sciatic nerve trunk oligemia and hypoxia, but it is uncertain how early these abnormalities develop or which develops first. We studied young (4-week-old) rats after 6 or 16 weeks of STZ-induced diabetes (or after citrate buffer injection in controls) by recording multi-fiber conduction in three different nerve territories and by measuring sciatic endoneurial blood flow (NBF) and oxygen tension (PnO2) at end point. To evaluate the impact of sympathectomy on this diabetic model, separate animal groups were treated for 5 weeks with guanethidine monosulfate given at the onset of diabetes (group 1, end point 6 weeks) or after 6 weeks of diabetes (group 2, end point 16 weeks). Diabetes was associated with deficits in sensory and motor caudal conduction and increased resistance to ischemic conduction failure (RICF). NBF was comparable to control animals at both time points and was within the published normal range of NBF. In contrast, oxygen tensions were shifted to lower values in diabetic animals. Sympathectomy was associated with blunting of the RICF increase in group 2 but worsened caudal sensory conduction despite evidence of modest improvement in sciatic nerve oxygenation. Our findings support the concept that neuropathy occurs early in diabetes and that hypoxia develops before oligemia. Sympathectomy did not benefit this diabetic model. PMID- 1423008 TI - Influence of pregnancy on mean systemic filling pressure and the cardiac function curve in guinea pigs. AB - To assess the degree of circulatory fullness and to evaluate the influence of peripheral and cardiac factors in the regulation of cardiac output during pregnancy, the following studies were conducted using pentobarbital-anesthetized, open-chest nonpregnant and late term pregnant guinea pigs. Mean circulatory filling pressure was taken as the equilibrium pressure when the pulmonary artery was constricted. Total vascular compliance was assessed by +/- 5-mL changes in blood volume performed while this constriction was maintained. A separate group of guinea pigs was prepared with a pulmonary artery electromagnetic flow probe and right atrial catheter. Rapid infusion of saline was used to increase right atrial pressure while the cardiac output was determined. Pregnancy was characterized by the following changes relative to nonpregnant controls: 51Cr labelled RBC blood volume increased from 55 +/- 3 to 67 +/- 3 mL/kg; mean circulatory filling pressure increased from 7.1 +/- 0.2 to 8.0 +/- 0.5 mmHg (1 mmHg = 133.322 Pa); right atrial pressure decreased from 3.4 +/- 0.2 to 2.1 +/- 0.3 mmHg; and cardiac output increased from 71.8 +/- 3.9 to 96.8 +/- 3.3 mL.min 1.kg-1. Total vascular compliance was not changed (2.1 +/- 0.1 mL.kg-1.mmHg-1) and most of the expanded blood volume was accommodated as unstressed volume. The cardiac function curve was shifted upwards in pregnant animals. The resistance to venous return, as determined from the slope of the venous return curves, was not changed. These data suggest that the circulation of the pregnant guinea pig is slightly overfilled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423010 TI - Comparison of the release of vasoactive factors from venous and arterial bovine cultured endothelial cells. AB - The release of endothelium-derived relaxing factor (EDRF), prostacyclin (PGI2), and endothelin-1 (ET-1) was measured from endothelial cells (EC) cultured from either bovine vena cava (BVCEC) or bovine aorta (BAEC). EDRF release was determined by using the superfusion bioassay technique, whereas ET-1 and PGI2 were measured by specific radioimmunoassays. Bradykinin (BK) (0.05-30 pmol) given through columns of venous or arterial EC induced a dose-dependent release of EDRF. BK (0.05 pmol) evoked a release of EDRF from venous EC that was similar to the effect of a dose of 1 pmol from arterial EC. As with BAEC, infusions of NG monomethyl-L-arginine (30 microM) caused an inhibition of EDRF release from BVCEC that was partially reversed by coinfusions of L-arginine (L-Arg; 100 microM). BK also induced a dose-dependent release of PGI2 from BVCEC. BVCEC and BAEC produced PGI2 in equivalent amounts when arachidonic acid (9.2 and 32 pmol) was added to the Krebs' solution perfusing the cells. BVCEC and BAEC released detectable amounts of ET-1 (0.4 +/- 0.1 and 0.9 +/- 0.3 ng/mL, respectively), over a 4-h period, and the release of ET-1 was increased approximately twofold by coincubations with thrombin (0.05-1 U/mL). These findings demonstrate that venous EC have a similar capacity to arterial EC to release vasoactive factors, thus supporting the hypothesis that veins have a functional endothelium that may modulate venous tone and platelet function. PMID- 1423009 TI - Effect of omega-3 fatty acids, docosahexaenoic and eicosapentaenoic, on norepinephrine-induced contractions. AB - The relaxant responses of the rat thoracic aorta to omega-3 fatty acids, docosahexaenoic and eicosapentaenoic, on norepinephrine- and potassium-induced contractions were investigated. Relaxation was enhanced in vessels contracted with norepinephrine. Docosahexaenoic acid at concentrations as low as 1, 3, and 10 microM evoked significant relaxant responses (15, 23, 30%) in norepinephrine contracted vessels as compared with responses (5, 9, 12%) in potassium-contracted vessels. Results for eicosapentaenoic acid under similar conditions were 3, 8, and 19% in norepinephrine-contracted vessels and 3, 3, and 8% in potassium contracted vessels. Pretreatment with eicosapentaenoic (10 microM) or docosahexaenoic acids (1-10 microM) decreased the contractile response to physiologic concentrations of norepinephrine. In the presence of calcium-free medium, the omega-3 fatty acids (1-30 microM) significantly abolished sustained norepinephrine contractions but did not reduce the phasic contractions when incubated prior to norepinephrine contraction. Comparatively, the effects of docosahexaenoic acid were greater than eicosapentaenoic acid. These findings suggest that the relaxant effects of the omega-3 fatty acids are specific to the mode of contraction, i.e., alpha-adrenoceptor stimuli. This effect may be related to intracellular calcium mechanisms, since both fatty acids reversed norepinephrine-induced sustained contractions in the absence of extracellular calcium. PMID- 1423011 TI - Role of corticosteroids in distal acidification of amiloride-treated rats. AB - The role of amiloride-dependent sodium channels in the action of adrenal cortical steroids on urine-blood PCO2 (U-B PCO2) differences was studied in bicarbonate infused and amiloride-treated adrenalectomized rats. U-B PCO2 was significantly reduced by amiloride in bicarbonate-infused control rats. Adrenalectomy further reduced U-B PCO2 in amiloride-treated, bicarbonate-infused rats (from 27.9 +/- 1.82 mmHg in sham-operated rats to 21.3 +/- 1.58 mmHg in adrenalectomized (ADX) rats) (1 mmHg = 133.322 Pa). Acute administration of corticosterone and 18 hydroxycorticosterone (18-OH-B), but not of aldosterone, caused recovery of U-B PCO2 to the level of sham-operated animals treated with amiloride. Aldosterone did not affect U-B PCO2 in the presence of amiloride (21.9 mmHg ADX group vs. 20.98 mmHg aldosterone group). Results are compatible with aldosterone affecting distal H ion secretion mostly by a sodium and potential difference dependent mechanism, while corticosterone and 18-OH-B should act by other mechanisms (e.g., increased luminal buffer level). PMID- 1423012 TI - Hypertension during chronic exposure to cold: comparison between Sprague-Dawley and Long-Evans strains. AB - It is now well established that chronic exposure of rats to cold (5-6 degrees C) induces an elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy within 3 weeks. Since rats of the Long-Evans (LE) strain are known to be resistant to the induction of deoxycorticosterone salt induced hypertension, their cardiovascular responses to chronic exposure to cold were compared with those of rats of the Sprague-Dawley (SD) strain. The results of these studies revealed clear differences between the LE and SD strains of rats. Thus, rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine and epinephrine; a significantly greater dipsogenic responsiveness to acute administration of angiotensin II, and significant increases in weights of the heart, kidneys, adrenals, and brown adipose tissue compared with their warm-adapted controls. All of these changes are characteristic of rats acclimated to cold. In contrast, rats of the LE strain appear to be less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level. Furthermore, urinary outputs of norepinephrine and epinephrine were significantly lower in cold treated rats of the LE strain compared with cold-treated rats of the SD strain, but dipsogenic responsiveness to angiotensin II was unchanged. Although increases in the weight of the previously mentioned organs were also observed in cold treated rats of the LE strain compared with their warm-adapted controls, weights of the heart and interscapular brown adipose tissue of both groups were significantly less than those of counterparts of the SD strain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423013 TI - Intratracheal injection of nickel chloride and copper-zinc superoxide dismutase activity in lung of rats. AB - Superoxide radical (O2-) is a free radical that may be involved in various toxic processes. Cu--Zn superoxide dismutase catalyses the dismutation of the superoxide free radical and protects cells from oxidative damage, and it has been used clinically. The concentration of Ni2+ and Cu--Zn superoxide dismutase activity were measured in lungs of rats at time intervals of 5, 12, 19, 26, 33, and 40 days following an intratracheal injection of 127 nmol of NiCl2. Nickel chloride increased nickel content and resulted in a significant increase of Cu- Zn superoxide dismutase activity in lungs. This elevation of Cu--Zn superoxide dismutase activity was highest on the 12th day (approximately threefold) and is at levels comparable to controls rats on day 40 onwards. Since Cu--Zn superoxide dismutase activity was increased in lung throughout our experimental period without corresponding increases of Cu2+ and Zn2+, we speculate that the elevation of Cu--Zn superoxide dismutase activity might be due to an increased half-life of the enzyme, induced by nickel. PMID- 1423014 TI - Competitive antagonism of pressor responses to angiotensin II and angiotensin III by the angiotensin II-1 receptor ligand losartan. AB - Losartan (DuP 753) and PD123177 are nonpeptide angiotensin (ANG) receptor ligands for subtypes of ANG II receptors ANG II-1 and ANG II-2, respectively. We examined the effects of losartan and PD123177 on dose - mean arterial pressure (MAP) response curves for ANG II and ANG III in eight groups (n = 6 each) of conscious rats. Saline (0.9% NaCl), losartan (1 x 10(-6) and 9 x 10(-6) mol/kg), and PD123177 (2 x 10(-5) mol/kg) were i.v. bolus injected 15 min before the construction of ANG II dose - response curves in groups I, II, III, and IV, respectively. Groups V-VIII were treated similarly to I-IV except that ANG III was given in place of ANG II. Losartan dose dependently shifted the dose-response curves of ANG II and ANG III to the right with similar dissociation constants ( log KI of 6.6 +/- 0.7 and 6.6 +/- 0.1 mol/kg, respectively) and no change in the maxima. PD123177 affected neither maximum MAP nor ED50 values for ANG II or ANG III. Our results show that losartan but not PD123177 is a competitive antagonist of the MAP effects of ANG II and ANG III. PMID- 1423015 TI - Production of tumour necrosis factor by cells exposed to sulphonamide reactive metabolites. AB - Hypersensitivity reactions are the most common adverse events associated with therapy with the sulphonamide antibiotics. These reactions have been shown to occur among individuals with pharmacogenetically determined differences in the capacity of their cells to detoxify reactive products of oxidative metabolism of the sulphonamides. These reactions appear to be propagated by an inflammatory response by the immune system. To investigate the role of the cytokine tumour necrosis factor (TNF-alpha) in these reactions, we studied the production of TNF alpha by peripheral blood mononuclear cells (PBMCs) that had been incubated with sulfamethoxazole and murine microsomes in the presence and absence of a microsomal-activating system and TNF-alpha production by PBMCs in the presence and absence of the hydroxylamine derivative of sulfamethoxazole. The PBMCs showed a time-related increase in the production of TNF-alpha. There was no increase in TNF-alpha production seen during incubation with sulphonamide reactive metabolites; rather, there was a decrease in TNF-alpha elaboration that was most marked when PBMCs were incubated with the hydroxylamine of sulfamethoxazole. There is no evidence from these in vitro studies that TNF-alpha is involved as a mediator of the inflammatory response in sulphonamide hypersensitivity adverse drug reactions. PMID- 1423016 TI - Digitaloid pregnanes promote potassium-sparing diuresis in the guinea pig. AB - The synthesis of 17 alpha-acetoxy-3 beta-[(beta-D-glucopyranosyl)oxy]- 6 alpha methylpregn-4-en-20-one, the glucoside of medroxyprogesterone acetate (MPA-glu), is described. MPA-glu and 14-amino-20 beta-hydroxy-3 beta-[(alpha-L rhamnopyranosyl)oxy]-5 beta, 14 beta-pregnane (LND 623), pregnane glycosides that bind to the digitalis receptor, and digoxin, a cardiac glycoside, were infused intravenously into the anesthetized guinea pig. Each of the three steroids significantly enhanced urinary volume and sodium excretion without affecting blood pressure and creatinine clearance. Potassium excretion was markedly enhanced by digoxin but unaffected by MPA-glu or LND 623. These observations conform to previous work that demonstrated, in the rat, potassium-sparing diuresis by the glucoside of 14 beta-hydroxyprogesterone, a cardiotonic pregnane. There is a dissociation between potency to inhibit [3H]ouabain binding and the extra ATPase actions of the digitaloid pregnanes. PMID- 1423017 TI - Differential effects of blood insulin levels on microsomal enzyme activities from hepatic and extrahepatic tissues of male rats. AB - Microsomal glutathione S-transferase, UDP-glucuronyl transferase, and aniline hydroxylase activities were determined in liver, renal cortex, and small intestine of control, streptozotocin-diabetic, alloxan-diabetic, and untreated insulin-injected male Wistar rats. Renal microsomal glutathione S-transferase activity showed a direct linear relationship with insulin blood levels, in agreement with our previous report on cytosolic glutathione S-transferase. This result suggests a possible regulatory mechanism of insulin that needs to be further examined. The hepatic microsomal UDP-glucuronyl transferase was only decreased in streptozotocin-diabetic rats and was not restored by insulin treatment. Intestinal UDP-glucuronyl transferase exhibited an opposite response in streptozotocin-treated animals that was not normalized by the administration of insulin. Hepatic aniline hydroxylase showed the same behaviour as intestinal UDP-glucuronyl transferase. These results suggest that streptozotocin and (or) its metabolites have a direct effect on hepatic and intestinal UDP-glucuronyl transferase activity and on hepatic aniline hydroxylase activity. On the other hand, insulin regulation of enzyme activity varies from one organ to another. PMID- 1423018 TI - Anatomy of the renal innervation: intrarenal aspects and ganglia of origin. AB - The intrinsic innervation of the kidney is described based on studies using ultrastructural, fluorescent, immunocytochemical, and autoradiographic techniques. The efferent sympathetic innervation reaches all the segments of the renal vasculature and to a much lesser extent the tubular nephron. The afferent renal nerves are localized predominantly in the pelvic region, the major vessels, and the corticomedullary connective tissue. The pathways of the renal innervation to the corresponding ganglia, as reported from observations resulting from the combination of axonal transport labeling and immunocytochemical methods, are presented. In the rat the ganglia of origin of the sympathetic efferent innervation include T13-L1 ipsilateral and contralateral paravertebral ganglia and the prevertebral superior mesenteric and celiac ganglia. The sensory afferent innervation presents a different segmental distribution of the dorsal root ganglia for the right and left kidney. For the left kidney, the corresponding ganglia extend from T8 to L2 with the greatest numbers in T12 and T13. For the right kidney, ganglia as high as T6 and as low as L2 harbor neurons innervating the kidney. Current knowledge of the anatomical bases of the function of the renal nerves is discussed. PMID- 1423019 TI - Neuronal control of the kidney: contribution to hypertension. AB - The renal nerves contribute to hypertension in experimental models of the disease, and appear to play a role in human hypertension. Several lines of evidence indicate that both in spontaneously hypertensive rats and in deoxycorticosterone acetate--NaCl rats, the full development of hypertension is dependent on renal efferent nerves and their induction of excess sodium retention. Renal sensory (afferent nerve) feedback to the central nervous system does not contribute to either of these forms of hypertension. In contrast, renovascular hypertension in rats and aortic coarctation hypertension in dogs are mediated, at least in part, by overactivity of renal afferent nerves and a resultant increase in systemic sympathetic nervous system activity. These forms of hypertension are not associated with sodium retention, and selective sensory denervation of renal afferent nerves by dorsal rhizotomy and total renal denervation result in similar reductions in hypertension. Surprisingly, the renal nerves do not contribute to dietary NaCl exacerbated hypertension in the spontaneously hypertensive rat, dietary NaCl-induced hypertension in the Dahl NaCl-sensitive rat, or the chronic hypertensive and nephrotoxic effects of cyclosporine A therapy in the rat, despite the finding that in all three forms of hypertension, overactivity of the sympathetic nervous system is prominent. Clinical studies indicate that the renal afferent and efferent nerves contribute to hypertension of different etiologies. Together these data point to the complex role that the renal nerves likely play in human essential hypertension. PMID- 1423020 TI - Central peptidergic mechanisms controlling reproductive hormone secretion: novel methodology reveals a role for the natriuretic peptides. AB - A variety of neural factors can influence reproductive hormone secretion by neuromodulatory actions within the hypothalamus or neuroendocrine actions within the anterior pituitary gland. Passive immunoneutralization and antagonist administration protocols have suggested physiological roles for a number of these factors; however, both experimental approaches have severe technical limitations. We have developed novel methodology utilizing cytotoxin cell targeting with neuropeptides linked to the toxic A chain of the plant cytotoxin ricin. With this methodology we can target and destroy in vivo or in vitro cells bearing receptors for that peptide. Ricin A chain conjugated to atrial natriuretic peptide (ANP), a neuropeptide known to pharmacologically inhibit luteinizing hormone-releasing hormone (LHRH) release, was injected into the cerebroventricular system of intact, cycling rats and ovariectomized rats. Cytotoxin conjugate treatment significantly lengthened the estrous cycle. In ovariectomized rats the luteinizing hormone surge induced by steroid priming was completely inhibited. LHRH content of the median eminences of these rats was not significantly altered. These data suggest that ANP binding to clearance receptors in the hypothalamus displaces the C-type natriuretic peptide (CNP) from the shared clearance receptor, making more CNP available to inhibit LHRH release. In the absence of cells bearing the clearance receptor all available CNP binds to the ANPR-B receptor and exerts its effect via an inhibitory interneuron, since LHRH fibers are spared by this treatment. PMID- 1423021 TI - Central actions of angiotensin in cardiovascular control: multiple roles for a single peptide. AB - Angiotensin II (ANG II) acts peripherally as a hormone, with actions on the vasculature, adrenals, and kidney. In addition, certain actions of ANG II in the central nervous system are directed toward cardiovascular control and fluid volume homeostasis. Dense binding sites for ANG II are found at circumventricular organs, which apparently have the ability to relay information to cardiovascular centers via neural circuitry. Microinjection of ANG II into the subfornical organ (SFO) or area postrema (AP) produces site-specific increases in blood pressure. In addition, electrophysiological studies demonstrate profound effects of ANG II, acting at the SFO, on activity of neurohypophysial neurons and release of oxytocin and vasopressin, which can be antagonized by ANG II blockers or attenuated by SFO lesions. Evidence from microinjection, electrophysiological, and lesion studies indicate a complex interaction between central sites involved in mechanisms of cardiovascular control: the SFO, AP, organum vasculosum of the lamina terminalis, and paraventricular and supraoptic nuclei of the hypothalamus. Not only is ANG II a humoral messenger in this central scenario, but evidence suggests it acts as a neurotransmitter or neuroendocrine substance within specific CNS pathways, suggesting multiple roles for this peptide in central cardiovascular control. PMID- 1423022 TI - Central arginine vasopressin and endogenous antipyresis. AB - Arginine vasopressin (AVP) is a centrally synthesized nonapeptide that exerts classical endocrine effects as well as a host of centrally mediated actions. A strong case can be argued in support of a neurotransmitter-neuromodulator role for AVP. Acting within the central nervous system (CNS), AVP has been demonstrated to be involved in the modulation of febrile body temperature. Because AVP acts to reduce pyrogen-induced fevers, but not normal body temperature, its actions are deemed to be antipyretic. However, to demonstrate an endogenous antipyretic function, AVP must be shown to be active during conditions where fever is naturally suppressed. This review will focus on five such conditions where the absence of pyrogen-induced fever can be linked to the endogenous activity of AVP within the brain. In the neonatal rat pup, the use of specific antagonists to the AVP receptor has revealed a role for CNS AVP in the absence of fever following peripheral injections of bacterial endotoxin. These results may help to explain a similar lack of fever in other newborn species. In parturient animals a reduced or absent febrile response has been linked to the increased presence of AVP within the septal area of the brain. The combined use of AVP receptor antagonism as well as immunohistochemistry has shown enhanced AVP activity within the ventral septal area of the rat and guinea pig brain during tolerance to intravenous pyrogens. These results suggest that the mechanism of fever suppression following repeated systemic injections of bacterial pyrogen includes centrally acting AVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423023 TI - Investigating the role of angiotensin II in thirst: interactions between arterial pressure and the control of drinking. AB - Several lines of evidence suggest that angiotensin II plays a physiological role in the control of thirst. Establishing that, however, has been surprisingly difficult, given our current knowledge about the renin-angiotensin systems in the circulation and the brain and the variety of techniques available to measure and manipulate them. A major problem is that stimulating or blocking the renin angiotensin system affects several physiological variables simultaneously. Since several of these variables also influence the controls of water intake directly or indirectly, the interpretation of the effect on drinking becomes more difficult. To illustrate the problem and recent developments, this paper describes some of the interactions between the effects of angiotensin II on arterial pressure and thirst, and it shows how they have contributed to the controversy over the physiological role of the peptide. PMID- 1423024 TI - Studies of the inhibitory activity of MK-0591 (3-[1-(4-chlorobenzyl)-3-(t butylthio)-5-(quinolin-2-yl-methoxy)-indol- 2-yl]-2,2-dimethyl propanoic acid) on arachidonic acid metabolism in human phagocytes. AB - We have investigated the inhibitory activity of compound MK-0591 (3-[1-(4 chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)-i ndol-2- yl]-2,2 dimethyl propanoic acid) on 5-lipoxygenase (5-LO) product synthesis in various human phagocytes stimulated with either the ionophore A23187, opsonized zymosan (OPZ), platelet-activating factor (PAF), or formyl-methionyl-leucyl-phenylalanine (fMLP). The lipoxygenase products were analyzed by reversed-phase HPLC. MK-0591 inhibited the formation of 5-hydroxyeicosatetraenoic acid, leukotriene (LT) B4, its omega-oxidation products, and 6-trans-isomers with IC50 values of 2.8-4.8 nM in A23187-stimulated neutrophils. In these conditions, arachidonic acid at a concentration of 10 microM had no effect on MK-0591 inhibitory activity. In neutrophils stimulated with OPZ, the synthesis of LTB4, its omega-oxidation products, and 6-trans-isomers was inhibited with IC50 values of 9.5-11.0 nM. MK 0591 inhibited 5-LO product synthesis in A23187-stimulated blood monocytes, eosinophils, and alveolar macrophages with IC50 values of 0.3-0.9, 3.7-5.3, and 8.5-17.3 nM, respectively. In neutrophils primed with granulocyte--macrophage colony-stimulating factor and stimulated with PAF, lipoxygenase product synthesis was inhibited with IC50 values of 7.7-8.7 nM. At the concentration of 1 microM, MK-0591 had no inhibitory effect on 15-lipoxygenase activity in human polymorphonuclear leukocytes, nor on human platelet 12-lipoxygenase and cyclooxygenase. In conclusion, MK-0591 is a very potent and specific inhibitor of 5-LO product synthesis in various types of human phagocytes. PMID- 1423025 TI - Effects of torbafylline on muscle atrophy: prevention and recovery. AB - The effects of torbafylline on the prevention of and the recovery from 5 weeks of hindlimb suspension induced atrophy were analyzed in rat soleus and extensor digitorum longus muscles. Muscle alterations were investigated by determining a suite of electrophysiological, histochemical, and muscle ultrastructural characteristics. Administration of torbafylline during the suspension period was ineffective in preventing any of the observed muscle atrophic changes. Application of torbafylline during the recovery period resulted in a faster recovery of some soleus muscle structural and functional properties. Mitochondrial volume densities and capillary to fiber ratios returned towards baseline values earlier in the recovery process with torbafylline. Furthermore, the drug significantly improved soleus muscle fatigue resistance 4 weeks after cessation of hindlimb suspension. PMID- 1423026 TI - Monophasic and biphasic effects of angiotensin II and III on norepinephrine uptake and release in rat adrenal medulla. AB - Angiotensin II and III have hypertensive effects. They induce vascular smooth muscle constriction, increase sodium reabsorption by renal tubules, stimulate the anteroventral third ventricle area, increase vasopressin and aldosterone secretions, and modify catecholamine metabolism. In this work, angiotensin II and III effects on norepinephrine uptake and release in rat adrenal medulla were investigated. Both angiotensins decreased total and neuronal norepinephrine uptake. Angiotensin II showed a biphasic effect only on evoked neuronal norepinephrine release (an earlier decrease followed by a later increase), while increasing the spontaneous norepinephrine release only after 12 min. On the other hand, angiotensin III showed a biphasic effect on evoked and spontaneous neuronal norepinephrine release. Both angiotensins altered norepinephrine distribution into intracellular stores, concentrating the amine into the granular pool and decreasing the cytosolic store. The results suggest a physiological biphasic effect of angiotensin II as well as angiotensin III that may be involved in the modulation of sympathetic activity in the rat adrenal medulla. PMID- 1423028 TI - Ca2+ transport through the brush border membrane of human placenta syncytiotrophoblasts. AB - The calcium (Ca2+) uptake by brush border membrane vesicles isolated from fresh human placentas has been characterized. This process was saturable and time- and concentration-dependent. It exhibited a double Michaelis-Menten kinetics, with apparent Km values of 0.17 +/- 0.03 and 2.98 +/- 0.17 mM Ca2+, and Vmax values of 0.9 +/- 0.13 and 2.51 +/- 0.45 pmol.micrograms-1.5 s-1. It was not influenced by the presence of Na+ or Mg2+ in the incubation medium. It was not increased by K+ or anion diffusion potentials, inside negative. At a steady state of 1 mM Ca2+ uptake, a large proportion (approximately 94%) of the Ca2+ was bound to the internal surface of the membranes. Preincubation of these membrane vesicles with voltage-dependent Ca2+ channel blockers (nifedipine and verapamil) had no influence on Ca2+ uptake. However, this uptake was very sensitive to pH. In the absence of a pH gradient, the Ca2+ uptake increased with alkalinity. When the intravesicular pH was kept constant while the pH of the incubation medium was increased, Ca2+ uptake was also stimulated by alkaline pH. In contrast, when the pH of the incubation medium was kept constant and the intravesicular pH was progressively increased, Ca2+ uptake was diminished with alkaline pH. Therefore, H+ gradient (H+ in trans-position greater than H+ in cis-position) favored Ca2+ transport, suggesting a H+/Ca2+ exchange mechanism. Finally, in contrast to the basal plasma membrane, the brush border membrane did not show any ATP-dependent Ca2+ transport activity. PMID- 1423027 TI - Trophic regulation of action potential in bullfrog sympathetic neurones. AB - These experiments tested the hypothesis that the normal electrophysiological properties of mature bullfrog sympathetic ganglion (BFSG) neurones are maintained by the retrograde supply of nerve growth factor-like molecules from peripheral target tissues. Maintenance of these cells in explant culture in the absence of nerve growth factor (NGF) for up to 30 days produced electrophysiological changes that resemble those previously shown to accompany axotomy in vivo. These included (i) an increase in action potential (ap) duration (spike width), (ii) a decrease in the amplitude of the afterhyperpolarization (ahp), which follows the ap, and (iii) a rapidly developing decrease in ahp duration. When murine NGF (2.5 s; 50 ng/mL) was included in the culture medium there was less attenuation of ahp amplitude. Inclusion of affinity-isolated sheep IgG antibodies (0.5 micrograms/mL; raised against murine 2.5 s NGF) in the culture medium promoted a greater reduction in ahp amplitude than was seen in the "control" explants that were maintained in the absence of NGF. By contrast, the decrease in ahp duration that occurred in control explants was neither attenuated by exposure to NGF nor was it enhanced by NGF antibodies. Also, the increase in spike width that was seen in control explants was enhanced both by murine NGF and by NGF antibodies. Although some of the data support the hypothesis that factor(s) with some similarity to NGF may be synthesized by BFSG in vitro, loss of the retrograde transport of such factors does not explain all aspects of the electrophysiological response to target deprivation and (or) axotomy. PMID- 1423029 TI - Conserved charge of glomerular and mesangial cell proteoglycans: possible role of amino acid-derived sulphate. AB - Sulphation of proteoglycans was studied in isolated glomeruli and cultured rat mesangial cells. Both preparations produced heparan, dermatan, and chondroitin sulphates, recoverable both from the tissue layers and the conditioned media. The proportion of heparan sulphate made by mesangial cells was independent of the age of the culture, but declined in later passage. These preparations differed from several other nontransformed cell types studied to date in that the degree of proteoglycan sulphation was independent of the concentration of inorganic sulphate provided. Even when no exogenous sulphate was added, sulphation dependent charge density of newly synthesized proteoglycans was conserved. Both isolated glomeruli and cultured mesangial cells produced proteoglycans with 35S labelled sulphate esters when [35S]methionine was provided as the sole source of labelled sulphate. Conversion of methionine to cysteine and subsequent oxidation of organic sulphate via the sulphinyl pyruvate pathway is the only mechanism known in eukaryotic cells that can account for this observation. We conclude that facile oxidation of sulphur-containing amino acids can contribute to sulphation of glomerular proteoglycans and may serve to sustain the charge density of these multifunctional molecules when the supply of inorganic sulphate is otherwise compromised. PMID- 1423030 TI - Improved sensitivity of the mouse interstitial cell testosterone assay with the addition of forskolin. AB - Modification of the mouse interstitial cell testosterone assay by the addition of 1.5 microM forskolin to the incubation medium has improved the sensitivity of this luteinizing hormone bioassay from approximately 100 to 3 pg/tube of NIH rLH RP-2. Luteinizing hormone can be clearly detected in 1 microL of serum from rats castrated 1 week previously and 5 microL of serum from intact rats. Parallelism was noted between dilution curves of serum from intact and castrated rats, and the luteinizing hormone standard curve. Luteinizing hormone detected in serum samples from 30 intact rats by the improved bioassay and by radioimmunoassay was significantly correlated (r = 0.85). Secretion patterns of circulating luteinizing hormone in individual rats were similar when detected by either bioassay or radioimmunoassay. Thus, with the addition of forskolin, the mouse interstitial cell testosterone assay has been improved so that luteinizing hormone can be detected in small volumes of serum or plasma from male rats. PMID- 1423031 TI - Vasodepressor reaction induced by inferior vena caval occlusion and isoproterenol. AB - Testing for the susceptibility for vasodepressor reaction in humans involves the combination of restriction of venous return by passive upright tilting and the administration of isoproterenol. To explore the basis of the vasodepressor test in humans, the present experiment examined whether a reduced cardiac volume coupled with adrenergic stimulation causes a vasodepressor reaction in rats. Vasodepressor reaction was defined as paradoxical heart rate slowing in conjunction with hypotension during inferior vena caval occlusion. Inferior vena caval occlusion was performed for 60 s and the maximum changes in R-R were measured during seven states as follows. (A) Under control conditions inferior vena caval occlusion alone accelerated the rate in 32 of 32 rats (delta R-R, 13.9 +/- 1.7 ms, p less than 0.001). (B) When inferior vena caval occlusion was performed during an infusion of isoproterenol (0.5-1.0 micrograms.min-1), a vasodepressor reaction was observed in all rats as the heart rate slowed (delta R R, +138.1 +/- 14.8 ms, p less than 0.001). The vasodepressor reaction was further examined during isoproterenol and inferior vena caval occlusion under five additional states. (C) After atropine the vasodepressor reaction was unchanged (delta R-R, +132.7 +/- 24.8 ms, p less than 0.001). (D) After bilateral vagotomy the paradoxical slowing was eliminated. (E) After intrapericardial lidocaine the paradoxic slowing was eliminated. (F) After bilateral stellectomy nonsignificant slowing was still present, but this was markedly reduced when compared with B (p less than 0.001). (G) Following chronic chemical sympathetic denervation with 6 hydroxydopamine the paradoxic bradycardia was eliminated. CONCLUSIONS: (1) Reduced cardiac volume combined with adrenergic stimulation can stimulate a vasodepressor reaction; (2) the vasodepressor reaction requires signalling by the afferent but not efferent vagal fibers; (3) the bradycardia is mainly due to withdrawal of sympathetic efferent tone. PMID- 1423032 TI - Localization of the reflex pathway responsible for the vasodepressor reaction induced by inferior vena caval occlusion and isoproterenol. AB - Vasodepressor reactions were induced in 27 rats by a combination of inferior vena caval occlusion and an infusion of isoproterenol. A vasodepressor reaction was defined as paradoxical heart rate slowing during inferior vena caval occlusion. The R-R intervals were measured at 5-s intervals before, during, and after 60 s of inferior vena caval occlusion. The purpose of this study was to examine the role of the right and left vagus nerve and the right and left stellate ganglia in this reflex. Under control conditions inferior vena caval occlusion accelerated the rate (R-R, -15.9 +/- 0.9 ms). During an infusion of isoproterenol (0.5-1.0 micrograms.min-1), inferior vena caval occlusion produced paradoxical rate slowing, i.e., a vasodepressor reaction (R-R, +75.0 +/- 2.2 ms). The vasodepressor reaction was examined during inferior vena caval occlusion and isoproterenol under the following additional states: atropine methyl bromide or right vagotomy did not alter the reaction; left vagotomy eliminated the reaction; and right or left stellectomy greatly reduced the vasodepressor reaction. We conclude the following: (1) left vagal afferents mediate the vasodepressor reaction; (2) cardiac sympathetic fibers participate in the vasodepressor reaction by withdrawing efferent tone through the right stellate ganglion, and by generating the afferent signal, which triggers the vasodepressor reaction through the left stellate ganglion. PMID- 1423033 TI - The effects of sympathetic denervation on spontaneous ventricular defibrillation in the rat. AB - Ventricular tachycardia or ventricular fibrillation was electrically induced in 38 normal rats (group 1) and 24 sympathetically denervated rats (6 hydroxydopamine) (group 2). The time for spontaneous reversion to sinus rhythm was measured during (1) control, (2) isoproterenol, and (3) the combination of isoproterenol and phenylephrine. The time for spontaneous reversion was the same in both groups in the three states. The reversion time was prolonged threefold by isoproterenol, and restored to control values when phenylephrine was added to the infusion of isoproterenol. The tachycardia duration and the refractory period were inversely related: log10 (tachycardia duration) = 3.466-0.091 (refractory period). Ventricular tachycardia/fibrillation induction was examined as follows: (i) Ventricular tachycardia/fibrillation was induced in 100% of normal rats (group 1), but only 42% of the denervated rats (group 2, p less than 0.001); (ii) during isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of rats of both groups; and (iii) when phenylephrine was added to isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of group 1 rats versus 82% of group 2 rats, (p = NS). These observations suggest (1) the induction of ventricular tachycardia/fibrillation is highly dependent on intact sympathetic innervation, and (2) exogenous adrenergic agonists modulate the duration of ventricular fibrillation through their effects on ventricular refractory period, independent of sympathetic innervation. PMID- 1423034 TI - Exercise training has a heparin-like effect on lipoprotein lipase activity in muscle. AB - Lipoprotein lipase (LPL) is anchored with high affinity to heparan sulphate proteoglycans on the luminal surface of the capillary endothelium. The levels of pre-heparin perfusate LPL activity increased from 16 +/- 1 to 145 +/- 6 U/hindlimb (nine-fold increase) in hindlimb muscle of exercise-trained rats measured immediately after the last bout of work. At the same time, post-heparin perfusate LPL activity decreased from 63 +/- 2 to 13 +/- 1 U/hindlimb (p less than 0.001). These results provide evidence that exercise-training has a heparin like effect on capillary-bound LPL. The total amount of LPL (i.e., pre-heparin perfusate plus post-heparin perfusate) was twofold greater in the hindlimb of the trained animals versus the controls. The effect of exercise on muscle LPL activity appears to last for as long as 5 days after cessation of exercise. Serum triglycerides were reduced 38% and plasma free fatty acids increased fourfold. These results provide evidence that training increases the capacity to remove triglycerides from circulation. PMID- 1423035 TI - gamma-Aminobutyric acid activity in the olfactory bulb of the rat during the sexual cycle and response to olfactory stimuli. AB - Glutamic acid decarboxylase activity in the main and accessory olfactory bulbs throughout the sexual cycle of the rat was studied. The effect of male pheromonal secretion on enzyme activity during proestrus and estrus day was also tested. The enzyme activity showed circadian rhythm during the estrous cycle. This rhythm was disrupted during diestrus-2 afternoon in the main bulb and came back during proestrus afternoon. A different pattern of enzyme activity was present in the accessory bulb, since the circadian rhythm was altered during proestrus morning, returning during estrus afternoon. Male odor exposition did not change enzyme profile activity during proestrus day and during estrus morning in the main bulb. In contrast, in the accessory bulb the olfactory stimuli induced opposite changes to that found in rats from the vivarium during proestrus. Comparison of enzyme activity in olfactory stimuli-deprived rats with that of pheromone-stimulated rats during proestrus showed that male odor exposure specifically affects accessory bulb enzyme activity. It is concluded that the changes of the olfactory bulb GABAergic system during proestrus and estrus day, or that evoked by odor stimuli, demonstrate the discriminative response of this system between the accessory olfactory bulb and the main olfactory bulb. PMID- 1423036 TI - Reduced Ca(2+)-induced Ca2+ release from skeletal muscle sarcoplasmic reticulum at low pH. AB - The purpose of this investigation was to determine the effects of reduced pH on Ca(2+)-induced Ca2+ release (CICR) from skeletal muscle sarcoplasmic reticulum (SR). Frog semitendinosus fiber bundles (1-3/bundle) were chemically skinned via saponin treatment (50 micrograms/mL, 20 min), which removes the sarcolemma and leaves the SR functional. The SR was first depleted of Ca2+ then loaded for 2 min at pCa (log free Ca2+ concentration) 6.6. CICR was then evoked by exposing the fibers to pCa 5-7 for 5-60 s. CICR was evoked both in the absence of ATP and Mg2+ and in the presence of beta, gamma-methyleneadenosine-5'-triphosphate (AMPPCP, a nonhydrolyzable form of ATP) and Mg2+. Ca2+ remaining in the SR was then assayed via caffeine (25 mM) contracture. In all cases, CICR evoked at pH 6.5 resulted in larger caffeine contractures than that evoked at 7.0, suggesting that more Ca2+ was released during CICR at the higher pH. Accordingly, rate constants for CICR were significantly greater at pH 7.0 than at pH 6.5. These results indicate that reduced pH depresses CICR from skeletal muscle SR. PMID- 1423037 TI - Electrolytes, protein, and lactate dehydrogenase isozymes of parotid saliva in mineralocorticoid-treated rats. AB - Small quantities of parotid saliva were obtained from 7 of 11 rats in which hypokalemia was induced by treatment with deoxycorticosterone acetate (DOCA). Thirst in the treated rats was indicated by an increase in water consumption. A decrease of 28% in plasma potassium levels indicated that the DOCA-treated rats had become hypokalemic; chloride decreased 6-7% while sodium was unchanged. Saliva showed significant increases in potassium and protein and a decrease in sodium; lactate dehydrogenase-2 and -4 bands appeared darker on the electrophoretic profile. These changes are relevant to the clinical manifestations and diagnosis of hypokalemia. PMID- 1423038 TI - Biotransformation of glyceryl trinitrate by rat brain homogenate. AB - Incubation of glyceryl trinitrate (GTN) with 5% (w/v) rat brain homogenate (RBH) resulted in biotransformation of the organic nitrate vasodilator drug to a mixture of glyceryl-1,2-dinitrate (1,2-GDN) and glyceryl-1,3-dinitrate (1,3-GDN). Heating of the RBH at 100 degrees C for 5 min and (or) pretreatment with 5 mM N ethylmaleimide at 37 degrees C for 10 min demonstrated that about two-thirds of the GTN biotransformation activity was due to a sulfhydryl-dependent enzymatic process resulting in the predominant formation of 1,2-GDN, and that the remaining biotransformation activity was due to a sulfhydryl-dependent nonenzymatic process resulting in the selective formation of 1,3-GDN. In a preliminary experiment, nitric oxide formation was observed during the incubation of GTN with RBH under anaerobic conditions. These data support the idea that some of the therapeutic and adverse effects of GTN are mediated through its action in the central nervous system. PMID- 1423039 TI - Mechanism of cerebral vasospasm following subarachnoid hemorrhage in monkeys. AB - This paper reviews our recent studies on the mechanism of cerebral vasospasm following subarachnoid hemorrhage (SAH) in monkeys. Middle cerebral artery (MCA) vasospasm was maximal at 7 days, resolving by 14 days, and absent at 28 days after SAH. Arterial fibrosis was not detected during vasospasm, although there was intimal hyperplasia with fibrosis 28 days after SAH. On scanning electron microscopy, smooth muscle cells from vasospastic arteries had corrugated cell membranes and appeared similar to cells contracted pharmacologically, suggesting that vasospastic smooth muscle is contracted. Morphometric analysis of arteries obtained 7 days after SAH showed no significant increases in arterial wall area of vasospastic arteries compared with normal MCAs. The results suggest vasospasm in monkeys is not due to hypertrophy, hyperplasia, or fibrosis in the arterial wall. Vasospasm may be mainly vascular smooth muscle contraction, which damages the arterial wall, leading to secondary structural changes in the arterial wall which occur after angiographic vasospasm. PMID- 1423040 TI - During repetitive forebrain ischemia, post-ischemic hypothermia protects neurons from damage. AB - In rodents damage from repetitive transient cerebral ischemia is more severe than that seen with a single ischemic insult of similar duration. Mild hypothermia has been shown to be very effective in protecting the brain during single ischemic insults. We tested the protective effects of hypothermia in repetitive ischemic insults. We used the gerbil model of repetitive ischemia (three minutes ischemia repeated at one hourly intervals three times) and histological evaluation was done using the silver staining technique. Our study reveals that a decrease in body and scalp temperature by 1-2 degrees Celsius can significantly reduce neuronal damage in the cerebral cortex, CA1 region of the hippocampus and substantia nigra reticulata during repetitive ischemia. As the hypothermia was induced after the initial insult, we believe this offers an opportunity for intervention in the clinical settings. PMID- 1423041 TI - The influence of indomethacin and guanethidine on experimental streptozotocin diabetic neuropathy. AB - In diabetic animals, reduced endoneurial perfusion and oxygen content have been linked to neuropathic abnormalities and might be amenable to pharmacological manipulation. In streptozotocin-induced diabetic rats, we studied the influence of guanethidine adrenergic sympathectomy, indomethacin treatment and a combined strategy on: serial in vivo motor and sensory conduction, resistance to ischemic conduction failure, in vitro myelinated and unmyelinated conduction, endoneurial perfusion and endoneurial oxygen tension. Unlike previous work diabetic animals had normal endoneurial perfusion but lower endoneurial oxygen tensions after six months of hyperglycemia. Guanethidine worsened sensory conduction despite lower microvascular resistance and an improvement in endoneurial oxygen tension. In contrast, indomethacin improved motor and sensory conduction but not oxygen tension. These studies do not support a linkage between conduction deficits and early endoneurial microangiopathy in experimental diabetes. Indomethacin, or related agents may offer a new therapeutic approach toward diabetic neuropathy through a mechanism independent of the endoneurial microvasculature. PMID- 1423042 TI - Absence of HTLV-I and HTLV-II proviral genome in the brains of patients with multiple sclerosis and amyotrophic lateral sclerosis. AB - Previous studies have failed to provide serological evidence to incriminate a retroviral infection in the cause of multiple sclerosis. Gene amplification techniques have also failed to identify retroviral footprints in DNA from peripheral blood leukocytes. Here we provide evidence that proviral DNA of HTLV-I and HTLV-II is not found in the central nervous system tissues of patients with multiple sclerosis, patients with amyotrophic lateral sclerosis and controls. PMID- 1423043 TI - Excitatory amino acid receptor antagonist in murine motoneuron disease (the wobbler mouse). AB - Recent evidence has suggested a potential role for involvement of excitatory amino acids (EAA) in the pathogenesis of the neuron loss in motoneuron diseases. We have examined the ability of an antagonist of N-methyl-D-aspartate (NMDA) receptors to halt or retard the progression of neurological symptoms in a murine form of motoneuron disease. The wobbler mouse is an autosomal recessive mutant which develops progressive neurological symptoms secondary to motoneuron loss. Treatment of wobbler mice with the NMDA receptor antagonist (+)-5-methyl-10,11 dihydro-5H-dibenzo(a,d)cyclohepten-5, 10-imine maleate (MK-801) did not retard neurological deterioration as assessed by a semiquantitative clinical scale. We conclude that NMDA receptor activation is probably not involved in the pathogenesis of motoneuron loss in the wobbler mouse. PMID- 1423044 TI - The increased susceptibility of women to multiple sclerosis. AB - Many diseases with an auto-immune etiology have a skewed sex distribution. In the majority of instances, women are affected more frequently than men. A review of population studies demonstrates that the preponderance of women in multiple sclerosis (MS) is almost constant. We show that this preponderance is further increased in early as well as in late-onset cases, in familial cases as well as in MS twin pairs and that the HLA-DR2 allele, which has been associated with MS in Caucasian populations, is significantly more frequent in women than in men with MS. "Rules" have been established for multifactorial diseases; MS contravenes most of those rules. The skewed sex distribution in MS could be attributed to the known hormonal and gender influences on the immune response, as well as to genetic influences. PMID- 1423045 TI - The neurology of cobalamin. AB - The following review indicates that the impact of cobalamin on neurologic disease extends far beyond the traditional myelopathy of classical pernicious anemia. The delineation of a broad spectrum of inherited disorders of cobalamin processing has served to illustrate and precisely define each step in the normal absorption, transport and intracellular metabolism of this essential vitamin. Recent clinical work has extended the boundaries of acquired cobalamin deficiency to encompass a variety of neuropsychiatric disturbances without identifiable concomitant hematologic derangements and emphasized the utility and sensitivity of new laboratory tests. These findings will demand increased vigilance from clinicians so that atypical and subtle cobalamin deficiency states will be readily diagnosed. The wide range of neurologic dysfunction observed in both inherited and acquired disorders of cobalamin metabolism challenges basic scientists to delineate cobalamin's presumed important role in the normal development and homeostasis of the nervous system. PMID- 1423046 TI - Gliomas in families. AB - This is a descriptive study of 19 families with glial tumors. Twelve were identified prospectively from 178 consecutive, unrelated adults and children with newly diagnosed gliomas seen at a regional cancer center between 01 Jan 89 and 31 Mar 91 (6.7%). There were 45 affected members (42 confirmed); 30 males, 15 females, ages 4 months-78 years (median, 44.5 years; mean, 38.9 years). Two families had four affected members, three families had three, and the others two. All confirmed tumors were supratentorial and all, save one, contained an astrocytic element. Three additional members of two families had other brain or neuroectodermal tumors. These families were not unusually cancer prone and did not appear to have neurofibromatosis, tuberous sclerosis, or colonic polyposis. There was no consistent pattern of inheritance. PMID- 1423047 TI - Symptomatic dystonia: clinical profile of 46 Brazilian patients. AB - Dystonia is a syndrome characterized by sustained muscle contraction, provoking twisting and repetitive movements or abnormal postures. It may be classified according to etiology, as idiopathic or symptomatic. We studied 122 Brazilian patients with a dystonic syndrome. Of these, 46 (37.7%) had symptomatic dystonia. The most frequent cause was tardive dystonia (34.8%) followed by perinatal cerebral injury (30.4%). Other causes were stroke (13.0%), encephalitis (6.5%) and Wilson's disease (4.3%). Cranial trauma, mitochondrial cytopathy and psychogenic, were the least frequent causes with one patient in each category. The etiology in two patients could not be established. Perinatal cerebral injury and postencephalitic dystonia were seen in the younger age group, while post stroke and tardive dystonia were seen in the older age group. PMID- 1423048 TI - The role of magnetic resonance imaging in acute transverse myelitis. AB - Eighteen adult patients presenting with acute transverse myelitis (ATM) were evaluated using magnetic resonance imaging. Only 7 had abnormal scans showing an area of increased signal intensity within the cord solely on T2 weighted images; T1 weighted images were normal. The MRI abnormality did not correlate with the cause of the transverse myelitis, the extent of maximum neurological deficit, or the prognosis. A scan performed more than 5 days after the onset of disease was most likely to be positive. Even though the prognostic value of MRI in ATM may be limited, it remains a valuable technique for ruling out other causes of noncompressive spinal cord lesions, such as hemorrhage, vascular malformation, or tumor. PMID- 1423049 TI - Monitoring children treated with carbamazepine. PMID- 1423050 TI - Re: Current status of radiosurgery for arteriovenous malformations. PMID- 1423051 TI - Consensus statement on physician training for the treatment of dystonia with botulinum toxin. The Canadian Movement Disorders Group. PMID- 1423053 TI - Age distribution of animals persistently infected with bovine virus diarrhea virus in twenty-two Danish dairy herds. AB - The objectives of this study were to compare the age distribution of animals persistently infected (PI) with bovine virus diarrhea virus (BVDV) in 12 herds with clinical BVD compared to ten herds without clinical BVD and to examine the incidence of PI calves born after the oldest PI animal. Blood samples from all animals were tested for bovine virus diarrhea virus and antibodies. In five herds, blood samples were obtained from calves born after the whole herd had been tested. All calves born by PI dams were also blood tested. In herds with clinical BVD the median age of PI animals was 248 days and in herds without clinical BVD the median age was 144 days. There was no significant difference between the age of PI animals in herds with clinical BVD compared to herds without clinical BVD (p = 0.48) suggesting similar epidemiology of the occurrences of PI animals in the two herd categories. Thereafter, all herds were used to study the incidence of PI animals. A total of 129 PI animals were found. In ten herds with 72 PI animals the age range of PI animals was more than six months. In these herds 26.3% of the PI animals were born within the first two months after birth of the oldest PI animal, no PI animals were born 2- less than 6 months, 52.7% were born 6- less than 14 months, 6.9% were born 14- less than 22 months and 13.9% (all born by PI dams) were born later than 22 months after the oldest PI animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423052 TI - Changes in the bacterial flora of the upper and lower respiratory tracts and bronchoalveolar lavage differential cell counts in feedlot calves treated for respiratory diseases. AB - Serial nasopharyngeal swab and bronchoalveolar lavage cultures were used to estimate changes in the bacterial flora of the respiratory tracts of calves during the first month after arrival in the feedlot. Bronchoalveolar lavage (BAL) differential cell counts served to evaluate pulmonary inflammatory changes during this period. Two groups of calves were studied, one consisting of clinically normal controls (n = 60), the other, of cases (n = 59) which received treatment for respiratory disease (penicillin +/- trimethoprimsulfadoxine). A variety of organisms, including Pasteurella multocida, Pasteurella haemolytica, Haemophilus somnus, Mycoplasma bovis and Mycoplasma bovirhinis, were present in the upper and lower airways of both groups during the postarrival period. With the exception of M. bovis, an overall decline in the prevalence of these organisms was observed during the course of the study. In cases, there was a marked decrease in the number of Pasteurella spp. and H. somnus isolates immediately following treatment. For the Pasteurella spp., however, this effect was shortlived as they often appeared to recolonize the respiratory tract within eight days of terminating antimicrobial therapy. Treatment did not appear to affect the frequency of isolating M. bovis. Its prevalence, in both groups of calves, increased to levels approaching 100% during the course of the study. All Pasteurella spp. isolates were tested for susceptibility to several commonly used antimicrobials. Resistance was only evident among P. haemolytica isolated from cases and in every instance this was to a combination of penicillin, ampicillin and tetracycline. Significantly more isolates were resistant after treatment than before. There were BAL differential cell count abnormalities indicative of inflammation in both cases and controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423054 TI - Effects of Pasteurella haemolytica leukotoxic culture supernatant on bovine neutrophil aggregation. AB - Pasteurella haemolytica A1 leukotoxic culture supernatant was evaluated for its ability to cause aggregation of bovine peripheral neutrophils. Neutrophils were isolated by a hypotonic lysis method and incubated with zymosan-activated plasma (ZAP), leukotoxic culture supernatant, antileukotoxin serum, calcium and magnesium-free media, p-bromophenacyl bromide and protein kinase C inhibitors. Aggregation was evaluated by changes in infrared light transmittance. Leukotoxic culture supernatant caused neutrophils to aggregate, and this effect was significantly removed by preincubation with antileukotoxin serum. Aggregation to ZAP and leukotoxin was dependent on the presence of extra-cellular calcium. Activation of protein kinase C by phorbol myristate acetate induced aggregation which was reduced by staurosporine; however, aggregation to leukotoxin did not involve protein kinase C activation. Phospholipase A2 inhibition did not alter the aggregation response to ZAP or to leukotoxin. The in vitro measurement of neutrophil aggregation induced by the leukotoxin of P. haemolytica reflects cytoskeletal and other activation events that may contribute to the intense inflammatory process which this organism induces in the lungs of cattle. PMID- 1423055 TI - Relaxin is not associated with poor milk yield in the postpartum sow. AB - Porcine relaxin (pRXN) titers were measured in 109 plasma samples drawn between 24 and 120 h post-partum from good (n = 34), and poor (n = 25) milking sows and from sows (n = 12) exhibiting overt signs of hypogalactia located on six swine farms in Ontario. Mean plasma pRXN titers among the three groups at 24 h post partum were not significantly different although there was considerable variation. By 48 h however, the pRXN titers had declined markedly in all groups and between 72 and 120 h, pRXN was cleared from the plasma of all sows examined except one hypogalactic animal that had a titer of 1.13 ng/mL at 96 h. These results suggest that, although pRXN may be identifiable in the corpora lutea during the puerperium, it does not contribute to either hypogalactia or poor lactational performance in sows. The data also encourage the view that pRXN could be used at farrowing without deleterious effects on suckling. PMID- 1423056 TI - Development of a model ribosomal RNA hybridization assay for the detection of Sarcocystis and other coccidia. AB - Two regions of the primary structure of the small subunit rRNA of Sarcocystis muris bradyzoites were compared with nucleotide sequences of S. gigantea, Toxoplasma gondii, Plasmodium berghei and Mus musculus and used to design genus- and species-specific probes for the detection and identification of coccidia. Total cellular RNA of purified S. muris, S. cruzi, T. gondii and Eimeria nieschulzi and coccidia-infected tissues of mouse, ox, sheep and pig, were assayed using twenty-base oligomers labelled with 32P. Hybridization occurred at temperatures ranging from 21 degrees C to 41 degrees C or 51 degrees C. One probe detected only S. muris and another successfully hybridized to several members of coccidia, including S. muris, S. cruzi, T. gondii and E. nieschulzi. One ng of total cellular RNA was sufficient to yield detectable hybrids in slot blot assays. The excellent sensitivity suggests that rRNA-based probes are capable of detecting individual parasites, and can assay low levels of coccidial infections not detectable by other methods. The results of this study show that it is possible to customize the specificity of rRNA-based probes for diagnostic, epidemiological or taxonomic purposes. PMID- 1423057 TI - The effect of dietary sodium on right ventricular failure-induced ascites, gain and fat deposition in meat-type chickens. AB - Experiments were carried out using various levels of sodium (Na+) from NaCl or NaHCO3 to determine: 1) the level of Na+ required to induce ascites alone or in combination with cold temperature and 2) the effect of Na+ on weight gain and fat deposition in broiler chickens. In experiment 1, there were no cases of ascites using levels of Na+, from NaCl at 0.14% to 0.44% in the feed from day 3 or using added Na+, from NaCl at 0.0% to 0.12% in the water from day 3 with a level of 0.14% in the feed. There was no significant difference in 21 or 42 day body weight, feed conversion, or right ventricle:total ventricle (RV:TV) ratio between treatment groups. Day 3 to 4 body weight gains were significantly increased in all treatment groups with added Na+ (p less than 0.01). In experiment 2, with levels of added Na+, from NaCl, at 0.0% to 0.12% in the water with a level of 0.20% in the feed there were two cases of ascites, one at day 7 and one at day 40 at the 0.12% level. There were no significant differences in body weight at days 21 or 42 or in the RV:TV ratios between groups. Feed conversions were improved (p less than 0.01) with the lowest and highest levels of Na+ and a significant increase in day 3 to 4 body weight gain, with increasing Na+ in all treatment groups, was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423058 TI - Epidemiological studies of congo red Escherichia coli in broiler chickens. AB - This prospective cohort study was designed to confirm the association between Congo red binding Escherichia coli (CREC) and E. coli air sacculitis in commercial broilers. It was also designed to evaluate CREC as an air sacculitis risk factor and to explore the CREC relationship to other air sacculitis risk factors (poultry house temperature, air-ammonia levels, and presence of other diseases). In addition, this study was used to assess a possible role of the broiler-breeder flocks and hatchers in the spread of CREC air sacculitis. Congo red E. coli-associated airsacculitis risk was based on CREC exposure of the chicks in the hatchers. Breeder flocks with greater than 30 CREC colonies/plate from hatcher air sampling tests were placed in the high risk group; flocks with less than five CREC colonies/plate were placed in the low risk group. Increased risks of death due to air sacculitis (RR = 2.26), and increased death rates due to CREC air sacculitis (RR = 9.45) in high-risk flocks, identified CREC as an important air sacculitis risk factor. The attributable risk percent of CREC airsacculitis from hatcher exposure of CREC was 89.4%, pointing to the hatcher as the source of CREC infection. The association of specific broiler-breeder flocks to high levels of CREC in the hatchers, and subsequent air sacculitis, suggests that the broiler-breeders are the ultimate source of CREC. PMID- 1423059 TI - Salmonella enteritidis and other Salmonella in laying hens and eggs from flocks with Salmonella in their environment. AB - Seven Canadian layer flocks with Salmonella enteritidis in their environment were investigated to determine the numbers of hens infected with S. enteritidis, the localization of S. enteritidis in organs of infected hens and the numbers of S. enteritidis-infected eggs produced by two affected flocks. By a microagglutination test (MAT) using S. pullorum antigens, these flocks had more seropositive hens (mean 51.9 +/- 16.9%) than two Salmonella-free flocks (mean 13.0 +/- 4.2%). Culture of tissues of 580 hens (433 seropositive) from the seven flocks detected 26 (4.5%) S. enteritidis-infected hens from two flocks. In one flock, 2/150 hens were infected with S. enteritidis phage type (PT) 8, which was confined to the ceca, and no Salmonella spp. were isolated from 2520 eggs (one day's lay). In the second flock, where 24/150 hens were infected with S. enteritidis PT13, extraintestinal infection was found in nine hens and involved the ovaries and/or oviduct in two hens. Salmonella enteritidis PT13 was isolated from one sample of egg contents and from one sample of cracked shells from among 14,040 eggs (one day's lay) from this flock. The overall prevalence of S. enteritidis-contaminated eggs from the two flocks with infected hens was less than 0.06%. Other Salmonella spp. isolated were S. heidelberg from 58 hens (10%), and S. hadar, S. mbandaka and S. typhimurium from one hen (0.2%) each. The MAT with antigens of S. pullorum had a sensitivity of 81% and a specificity of 24% for detecting S. enteritidis-infected hens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423060 TI - Use of bacitracin in the prevention and treatment of experimentally-induced idiopathic colitis in horses. AB - Ten healthy ponies from a single herd were found by repeated fecal culture to be free of Salmonella species and Clostridium cadaveris. In a preliminary study, four ponies administered a single oral dose of 10 mg/kg lincomycin did not develop idiopathic colitis when the drug was administered alone. Four other ponies were administered 10 mg/kg lincomycin by stomach tube together with 0.45 L of colonic content from a horse with idiopathic colitis induced earlier by lincomycin alone. Two of the four ponies were treated with 25 g oral zinc bacitracin premix (110 g/kg active ingredient) 24 h later. Forty-two hours after inoculation the two untreated ponies had severe signs of idiopathic colitis and were euthanized. Postmortem findings were typical of idiopathic colitis. The two treated ponies had milder illness but the more severely affected was also euthanized; the other was retreated at 42 h with bacitracin pre-mix and again 12 h later. Its illness and diarrhea resolved over the next 24 h. Clostridium cadaveris was isolated in large numbers from the cecum of the euthanized ponies and their cecal content contained mouse lethal and guinea pig dermonecrotic, but not cytotoxic, activity. Enterotoxins of Clostridium perfringens and Clostridium difficile could not be demonstrated. No toxin could be demonstrated in culture supernatants of C. cadaveris or in supernatants of cecal contents treated with ethanol prior to culturing in anaerobically incubated broth. No Salmonella spp. were isolated. A further two ponies were administered 10 mg/kg lincomycin orally with 0.45 L colonic content from a horse with idiopathic colitis, as described.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423061 TI - Pathology of morbillivirus infection in striped dolphins (Stenella coeruleoalba) from Valencia and Murcia, Spain. AB - During the summer and fall of 1990 hundreds of striped dolphins (Stenella coeruleoalba) died in the Spanish Mediterranean as a result of morbillivirus infection. A pathological investigation was carried out on dolphins from Valencia and Murcia which were among the first to die in the epizootic. The dolphins were in poor body condition and pneumonia was the main necropsy finding. Microscopic lung lesions characterized by necrosis of bronchial and bronchiolar epithelium and infiltration of alveoli with macrophages, lymphocytes, neutrophils and multinucleated syncytia were seen in most dolphins. Cytoplasmic and nuclear eosinophilic viral inclusions were present in bronchial and bronchiolar epithelium and in syncytia. Focal granulomatous inflammation associated with nematodes was also present. Brain lesions included diffuse degeneration and necrosis of neurons, microgliosis, perivascular cuffing, formation of syncytia and focal demyelination. Cytoplasmic and nuclear eosinophilic inclusions were present in neurons and glial cells. There was severe lymphoid necrosis and depletion of spleen and lymph nodes and syncytia also occurred in lymph nodes. Biliary and transitional epithelium contained nuclear and cytoplasmic eosinophilic inclusions. Immunoperoxidase staining using monoclonal antibodies to phocine distemper virus confirmed the presence of morbillivirus antigens in lung and brain. The distribution and severity of lesions in striped dolphins are similar to those of distemper in seals, harbor porpoises and terrestrial mammals. The formation of syncytia in the lung and brain may be a useful pathological indicator of morbillivirus infection and may be used in the investigation of pinniped and cetacean strandings in North America. PMID- 1423062 TI - Liposomes targeted to deliver antisecretory agents to jejunal mucosa. AB - The B subunit of cholera toxin has been covalently attached to the surface of liposomes made from a mixture of phosphatidylethanolamine, phosphatidylcholine and cholesterol. Adenylate cyclase inhibitors and chloride conductance inhibitors were encapsulated within the liposomes. These "targeted" liposomes were used to study the combined effects of this novel delivery system, and a limited number of possible antisecretory agents, on net fluid flux into the pig jejunum. A state of net secretory fluid flux was induced in isolated jejunal loops in weanling pigs by adding theophylline or cholera toxin to the lumen of the isolated loops. There was no reduction in net fluid secretion when liposome suspensions without encapsulated secretory inhibitors were added to fluid in the lumen of loops treated with theophylline. There was also no reduction in net fluid secretion when miconazole, alpha-phenylcinnamate or 5 nitro-2-(3-phenethylamino)benzoate were encapsulated within targeted liposomes added to isolated jejunal loops. The net fluid flux induced by exposure of jejunal loops to theophylline was significantly reduced by adding targeted liposomes containing 2'-deoxy-3'-AMP. The reduction involved a reversal of net secretory fluid flux to an absorptive value. The net fluid secretory response to treatment of loops with cholera toxin was also inhibited by treating loops with targeted liposomes containing 2'-deoxy 3'-AMP. However, the reversal of secretion was less complete for secretion induced by cholera toxin than for secretion induced by theophylline. The reduced antisecretory efficacy versus cholera toxin was not improved by encapsulating higher concentrations of 2'-deoxy-3'-AMP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423063 TI - The effects of thiamin on lead metabolism: organ distribution of lead 203. AB - The effect of thiamin on the organ distribution of lead was evaluated in CD-1 mice exposed intragastrically or intraperitoneally to a single dose of lead acetate (100 micrograms) containing 100 microCi lead 203. They were treated with either thiamin (25 or 50 mg/kg body weight), calcium ethylenediaminetetraacetic acid (CaEDTA) (50 mg/kg body weight), or combinations of thiamin and CaEDTA. The whole body retention and the organ distribution of lead 203 varied depending upon the route of lead administration, dose of thiamin and the specific treatment combination. Thiamin (25 or 50 mg/kg) treatment increased the whole body retention of both intragastric and intraperitoneal lead by approximately 10% in each instance. Calcium ethylenediaminetetraacetic acid, either alone or in combination with thiamin (50 mg/kg) reduced the whole body retention of lead by as much as 14% regardless of route of lead exposure. The relative retention of lead by the liver, kidney and spleen was greater in mice exposed to lead by the intragastric route. Regardless of route, CaEDTA in the combined treatment reduced the relative retention of lead in both the liver and kidney, whereas thiamin alone only reduced the retention of lead in the kidney. The results of this study indicate that thiamin in combination with CaEDTA alters the distribution and retention of lead in a manner which may have therapeutic application as it relates to chelation therapy. PMID- 1423064 TI - Enhanced adherence of Pasteurella multocida to porcine tracheal rings preinfected with Bordetella bronchiseptica. AB - Adherence of 25 isolates of Pasteurella multocida to porcine tracheal rings was evaluated. Results indicated that adherence was not related to the isolate's origin, capsular or somatic types, dermonecrotoxin production or hemagglutination activity. The effect of a preinfection with Bordetella bronchiseptica on the colonization by P. multocida was then studied. On rings infected with P. multocida alone, bacteria initially adhered to the epithelium, but within a few hours, the level of colonization decreased progressively. On rings preinfected with B. bronchiseptica, or pretreated with a cell-free B. bronchiseptica culture supernate (or filtrate), a high level of P. multocida colonization was maintained for at least 24 hours. Results indicate that B. bronchiseptica appears to facilitate upper respiratory tract colonization by P. multocida by a process which involves a low molecular weight (less than or equal to 1000) heat-stable substance, possibly the tracheal cytotoxin. PMID- 1423065 TI - Secretion of alpha-hemolysin by bovine mammary isolates of Staphylococcus aureus. AB - A total of 262 strains of Staphylococcus aureus isolated from the mammary gland of dairy cows were examined for the production of alpha-hemolysin. Strains were cultured in a liquid medium of casein hydrolysate and yeast extract in an atmosphere of 7% (v/v) CO2 in air. The assay consisted of a dot immunoblotting technique employing bacterial culture supernatants and a mouse monoclonal antibody specific for alpha-hemolysin. Ninety-four percent (247) of 262 strains were positive for alpha-hemolysin by this method, when cultured in the laboratory. This figure is compared with those obtained in previous studies which typically based their results on the hemolytic patterns of isolates on blood agar plates. PMID- 1423066 TI - Homeopathy treats people, not the soles of their feet. PMID- 1423067 TI - Public education about breast cancer. PMID- 1423068 TI - Public education about breast cancer. PMID- 1423069 TI - Public education about breast cancer. PMID- 1423070 TI - Reproductive hazards and the workplace. PMID- 1423071 TI - Reviewing physicians' practices. PMID- 1423072 TI - A survey of resuscitation training in Canadian undergraduate medical programs. PMID- 1423073 TI - A survey of resuscitation training in Canadian undergraduate medical programs. PMID- 1423074 TI - Physicians and the pharmaceutical industry. PMID- 1423075 TI - The quest for quality begins in medical school. PMID- 1423076 TI - When to use advance treatment directives. PMID- 1423077 TI - When to use advance treatment directives. PMID- 1423078 TI - Drug nomenclature suggestions for change. PMID- 1423080 TI - Medical training in the United States. PMID- 1423079 TI - Drug nomenclature: suggestions for change. PMID- 1423081 TI - Salicylate poisoning. PMID- 1423082 TI - The Civil War comes to Queen's. PMID- 1423083 TI - Improving the treatment of out-of-hospital cardiac arrest. PMID- 1423084 TI - The Canadian National Breast Screening Study: a clinician's perspective. PMID- 1423085 TI - Prevention of occupational disease: problems of data collection for adequate surveillance. PMID- 1423086 TI - Periodic health examination, 1992 update: 4. Prophylaxis for gonococcal and chlamydial ophthalmia neonatorum. Canadian Task Force on the Periodic Health Examination. PMID- 1423087 TI - Canadian National Breast Screening Study: 1. Breast cancer detection and death rates among women aged 40 to 49 years. AB - OBJECTIVES: To evaluate the efficacy of the combination of annual screening with mammography, physical examination of the breasts and the teaching of breast self examination in reducing the rate of death from breast cancer among women aged 40 to 49 years on entry. DESIGN: Individually randomized controlled trial. SETTING: Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer. PARTICIPANTS: Women with no history of breast cancer and no mammography in the previous 12 months were randomly assigned to undergo either annual mammography and physical examination (MP group) or usual care after an initial physical examination (UC group). The 50,430 women enrolled from January 1980 through March 1985 were followed for a mean of 8.5 years. DATA COLLECTION: Derived from the participants by initial and annual self-administered questionnaires, from the screening examinations, from the patients' physicians, from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base. Expert panels evaluated histologic and death data. MAIN OUTCOME MEASURES: Rates of referral from screening, rates of detection of breast cancer from screening and from community care, nodal status, tumour size, and rates of death from all causes and from breast cancer. RESULTS: Over 90% of the women in each group attended the screening sessions or returned the annual questionnaires, or both, over years 2 to 5. The characteristics of the women in the two groups were similar. Compared with the Canadian population, the participants were more likely to be married, have fewer children, have more education, be in a professional occupation, smoke less and have been born in North America. The rate of screen-detected breast cancer on first examination was 3.89 per 1000 in the MP group and 2.46 per 1000 in the UC group; more node positive tumours were found in the MP group than in the UC group. During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.26 in the MP group and 1.02 in the UC group. Of the women with invasive breast cancer through to 7 years, 191 and 157 women in the MP and UC groups respectively had no node involvement, 55 and 43 had one to three nodes involved, 47 and 23 had four or more nodes involved, and 38 and 49 had an unknown nodal status. There were 38 deaths from breast cancer in the MP group and 28 in the UC group. The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 1.36 (95% confidence interval 0.84 to 2.21). The survival rates were similar in the two groups. The highest survival rate occurred among women whose cancer had been detected by mammography alone. CONCLUSION: The study was internally valid, and there was no evidence of randomization bias. Screening with yearly mammography and physical examination of the breasts detected considerably more node-negative, small tumours than usual care, but it had no impact on the rate of death from breast cancer up to 7 years' follow-up from entry. PMID- 1423088 TI - Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. AB - OBJECTIVE: To evaluate the efficacy of annual mammography over and above annual physical examination of the breasts and the teaching of breast self-examination among women aged 50 to 59 on entry. DESIGN: Individually randomized controlled trial. SETTING: Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer. PARTICIPANTS: Women with no history of breast cancer and no mammography in the previous 12 months were randomly assigned to undergo either annual mammography and physical examination (MP group) or annual physical examination only (PO group). The 39,405 women enrolled from January 1980 through March 1985 were followed for a mean of 8.3 years. DATA COLLECTION: Derived from the participants by initial and annual self-administered questionnaires, from the screening examinations, from the patients' physicians, from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base. Expert panels evaluated histologic and death data. MAIN OUTCOME MEASURES: Rates of referral from screening, rates of detection of breast cancer from screening and from community care, nodal status, tumour size and rates of death from all causes and from breast cancer. RESULTS: Over 85% of the women in each group attended the screening sessions after screen 1. The characteristics of the women in the two groups were similar. Compared with the Canadian population the participants were more likely to be married, have fewer children, have more education, be in a professional occupation, smoke less and have been born in North America. The rate of screen-detected breast cancer on first examination was 7.20 per 1000 in the MP group and 3.45 per 1000 in the PO group, more node-positive tumours were found in the MP group than in the PO group. At subsequent screens the detection rates were a little less than half the rates at screen 1. During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.28 in the MP group and 1.18 in the PO group. Of the women with invasive breast cancer through to 7 years, 217 in the MP group and 184 in the PO group had no node involvement, 66 and 56 had one to three nodes involved, 32 and 34 had four or more nodes involved, and 55 and 46 had an unknown nodal status. There were 38 deaths from breast cancer in the MP group and 39 in the PO group. The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 0.97 (95% confidence interval 0.62 to 1.52). The survival rates were similar in the two groups. Women whose cancer had been detected by mammography alone had the highest survival rate. CONCLUSION: The study was internally valid, and there was no evidence of randomization bias. Screening with yearly mammography in addition to physical examination of the breasts detected considerably more node-negative, small tumours than screening with physical examination alone, but it had no impact on the rate of death from breast cancer up to 7 years' follow-up from entry. PMID- 1423089 TI - Prevalence of antibody to human T-cell lymphotropic virus type I/II in people of Caribbean origin in Toronto. AB - OBJECTIVE: To estimate the prevalence of antibody to human T-cell lymphotropic virus type I/II (anti-HTLV-I/II) in people from an HTLV-I/II-endemic area (the Caribbean) living in a nonendemic region (Canada). DESIGN: Cross-sectional household survey. SETTING: Households in Toronto in 1989. PARTICIPANTS: A modified quota sampling method was used to recruit subjects of Caribbean origin as well as other Canadians. Of 2900 people invited to participate in the study 1323, 743 of Caribbean origin, were interviewed about their background and possible exposure to HTLV-I/II. MAIN OUTCOME MEASURES: Blood samples were analysed for anti-HTLV-I/II by means of an enzyme-linked immunoassay, the result being confirmed by the Western blot technique and radioimmunoprecipitation assay. The samples were also analysed for antibody to human immunodeficiency virus (anti HIV) and hepatitis B surface antigen (HBsAg) and for surrogate markers of non-A, non-B hepatitis. RESULTS: A total of 853 blood samples (64.5%) were analysed, 483 (56.6%) from subjects of Caribbean origin. The proportion of subjects who agreed to give a blood sample was similar for the Caribbean and non-Caribbean strata. Eleven subjects, all of Caribbean origin (2.3% of the Caribbean stratum), were confirmed to be positive for anti-HTLV-I/II. There were no significant differences between the antibody-positive and antibody-negative subjects with respect to sex, age, racial origin or residence in the Caribbean for at least 22 years. All anti-HTLV-I/II-positive subjects were negative for anti-HIV and HBsAg, and four (36.4%) were positive for antibody to HBsAg and to hepatitis B core antigen. CONCLUSIONS: Except for origin, an association between antibody positivity and other factors could not be demonstrated. The findings suggest that blood donor screening might include place of origin in addition to the usual lifestyle or behavioural factors. However, the need to ensure safety of transfusion must be balanced against the need for participation of all groups in the blood transfusion program. PMID- 1423090 TI - The nature of essential hypertension. PMID- 1423091 TI - Bombing of Toronto abortion clinic raises stakes in bitter debate. PMID- 1423092 TI - Microchips versus stethoscopes: Calgary hospital, MDs face off over controversial computer system. PMID- 1423093 TI - Health care issues given short shrift in US election campaigns. PMID- 1423094 TI - Doctor on hot seat in UK euthanasia row. PMID- 1423095 TI - IRCM celebrates 25 years of fulfilling crucial role in medical research in Quebec. PMID- 1423096 TI - Threat of nuclear war subsides, but antiwar MDs say lots of work remains. PMID- 1423097 TI - Several medical schools have begun to tackle sexual harassment issue. PMID- 1423098 TI - Providing Olympic-class care aim of Canadian medical team. PMID- 1423099 TI - MDs should warn patients that an extended trek south may be expensive venture. PMID- 1423100 TI - Physicians should warn patients about nutrition-related scams, doctor advises. PMID- 1423101 TI - Preventing STDs: education that influences adolescents' behaviour is needed. PMID- 1423102 TI - Attitudes about cancer and knowledge of cancer prevention among junior high students in Calgary, Alberta. AB - Results from a survey of junior high students conducted in preparation of curriculum materials on cancer prevention are reported. Students in the survey (n = 246) consider cancer to be a serious disease, not particularly amenable to treatment, and caused by many things. About half the students mentioned avoiding tobacco use as important in preventing cancer. However, 27% were unable to identify any ways to avoid getting cancer. Specific knowledge of dietary practices recommended to reduce cancer risk was poor, with fewer than 10% of students mentioning high fibre or low fat as important dietary habits. Knowledge of factors related to skin cancer was better, with 53% of students mentioning avoiding sun exposure as a way to reduce the risk of skin cancer. The majority of students (71%) wanted more information about cancer. The results from the survey indicate a need for cancer-prevention materials in the school curriculum. PMID- 1423103 TI - Linking research activities with policy and program design. PMID- 1423104 TI - Rural high school students' knowledge, attitudes and behaviours related to sexually transmitted diseases. AB - High school students are at high risk for contracting sexually transmitted diseases (STDs). A sample of 69 rural high school students from the province of Alberta, Canada were surveyed regarding their knowledge, attitudes and behaviours related to STDs to ascertain whether they differ from urban students. Results indicate that rural and urban high school students are similar in terms of knowledge about STDs, attitudes towards their prevention and also in terms of sexual behaviours. As with other studies, behaviours lagged behind knowledge and attitudes with reported condom use low. Sexual decision making was influenced mainly by the peer group. Males and females were mainly influenced by the same factors which include the willingness of their partner, the behaviours of their friends and family, concern about contracting a STD. These data emphasize the need to implement primary prevention programs for high school aged youth in rural as well as urban settings. PMID- 1423105 TI - Health behaviours in a Canadian community college sample: prevalence of drug use and interrelationships among behaviours. AB - This study investigated the prevalence of drug use among a Canadian college sample and the covariation of drug taking and other health-related behaviours. A representative sample of students at a community college in Alberta were interviewed using telephone surveys, mail-in questionnaires and face-to-face interviews. Data was collected on drug, alcohol and caffeine use, cigarette smoking, eating habits, sleep habits and exercise. While use of illicit drugs did not appear to be widespread, alcohol appeared to be a primary substance abuse problem for a minority of subjects. Factor analysis indicated that the various health habits did not form one dimension of health-related behaviours. Four separate factors emerged: abusive drinking, eating habits, a drug use factor (caffeine intake, smoking, cannabis and hallucinogen use), and exercise levels. Findings are discussed in terms of their implications for future research, treatment and intervention. PMID- 1423106 TI - Hospital response protocols for child sexual abuse and sexually transmitted diseases in children. AB - Hospitals are significant portals of entry to the health care system for children who have been sexually abused. Hospital staff have the opportunity to investigate, intervene in and prevent the cycle of abuse. Accordingly, several Canadian hospitals have standardized responses to meet the needs of the sexually abused child; however, the prevalence of protocols and the degree of standardization across the country have not been documented. A survey of hospitals in Canada indicated that 46% of hospitals that treated children had a response protocol for child sexual abuse and only 17% had a response protocol for sexually transmitted diseases in children. Protocols were more likely to be in place in hospitals that were accredited, specialized in paediatrics, were designated as teaching facilities for medicine, nursing and social work, and had more than 200 beds. In hospitals without protocols, staff were often not convinced of their need or desirability. PMID- 1423107 TI - Healthy communications: producing a health report (Infowatch) for monitoring and promoting health in local communities. AB - In order to bridge the gap between producers and users of community health data, we have developed a standardized format to provide a simple, comprehensive approach to the communication of epidemiologic data at the local level. Infowatch follows a series of format and style rules selected to enhance readability. The four-page format is divided into six sections: introduction and scope; "results" presented as charts, figures and text; policy implications (through consultation with community groups); methodological summary; references for self-study; and, invitation for reader feedback. An editorial committee comprising experts and representatives from local interest groups ensures that the data presented are relevant and of high quality. The content of each Infowatch issue varies depending on community priorities. Infowatch is distributed to 3,000 people, including representatives from health-related, academic, governmental and non governmental agencies. Five areas assess qualitatively the impact of Infowatch: reader, media, policy, education, and solicited responses. Overall, response from all categories has been favourable with evidence of infiltration into policy. PMID- 1423108 TI - Recent trends in morbidity and mortality rates for abdominal aortic aneurysms. AB - OBJECTIVES: To examine recent trends in mortality and morbidity rates from aortic aneurysms among Canadian seniors. DESIGN: Retrospective study. PARTICIPANTS: Men and women age 65 years or older who were hospitalized in Canada with a primary diagnosis of aortic aneurysm or whose underlying cause of death was aortic aneurysm. MAIN RESULTS: Unlike other circulatory diseases which have shown marked declines, mortality and morbidity rates from aortic aneurysms have remained constant over the last 10 years. Risks for male seniors are 4-5 times greater than for females. CONCLUSIONS: Since mortality and morbidity from aortic aneurysms have not decreased and screening offers potential benefits, costs and benefits of screening need to be quantified. PMID- 1423109 TI - Preparing health professionals for a collaborative health promotion role. AB - Practitioners and educators must consider whether or not the curriculum offered in a university setting by our health professional schools prepares the potential practitioner for work in the multisectorial, interdisciplinary milieu that has been recommended by The Alma Ata Declaration, the Epp Health Promotion document and the Ottawa Charter. I describe a final-year course in Community Health Nursing that is being offered by Dalhousie University School of Nursing. The course is open to generic and post-registration nurses. The course, based on adult learning principles, used a collaborative community development approach. The curriculum was designed to give baccalaureate student nurses the experience of participating in collaborative health promotion directed towards the strengthening of a community. Student, faculty, preceptor and service-based coordinators' evaluation of the two-year implementation of the course is described in the paper. PMID- 1423110 TI - The hepatitis B immunization strategy in Nova Scotia: is it effective? AB - Since 1987, both hepatitis B disease and hepatitis B vaccine utilization have increased dramatically in Nova Scotia. We present a review of hepatitis B vaccine utilization relative to the occurrence of disease in Nova Scotia. In the two regions with the highest incidence rates, cases have been increasingly associated with lifestyle-related risk factors. Vaccine utilization was primarily for occupational risks. The current provincial hepatitis B immunization strategy is to recommend immunization to targeted high-risk groups. This strategy was judged to be ineffective. The cost of the vaccine is the most important deterrent for adopting an expanded or universal immunization strategy. The pooling of hepatitis B vaccine orders across Canada is suggested as a means to effect significant reductions in the cost of vaccine. Provincial programs would then be able to expand coverage to include populations at immediate risk and youngsters prior to the start of high-risk activity. PMID- 1423111 TI - [Organization of prehospital emergency care in Canada: Elements of international and interprovince comparisons]. AB - Out of a comparative research conducted on the training of first respondents to car crash injuries, this paper identifies four major factors influencing the way in which a country designs its prehospital emergency system. The paper also discusses elements pertaining to the organization of these systems in Canada and presents relevant interprovincial variations. PMID- 1423112 TI - Diabetes-related lower extremity amputations in Ontario: 1987-88 experience. AB - Lower extremity amputee rates were estimated for diabetic persons living in Ontario. The rates were specified for age, sex and six Health Regions. The 1987 88 Hospital Records Institute database supplied the information regarding the amputations and the prevalence of diabetes in Ontario was estimated from age/sex specific diabetic rates of the U.S. The crude amputee rate for Ontario is 40 amputees/year/10,000 diabetics and the amputation rate is 44 amputations/year/10,000. These rates are lower than the 101 amputees/year/10,000 reported in the U.K. and are reasonably close to those of the U.S. (59.7 amputations/year/10,000). Age and sex Standardized Morbidity Ratios indicated that Region 1 and 6 have significantly higher and Region 2 significantly lower amputee rates than the Province. There is an almost two-fold difference between the highest and the lowest DRLEA rates of the six regions. (Range: 60-30). These results should be interpreted with caution, since actual prevalence rates of diabetes are not available. PMID- 1423113 TI - Aspects of preventive health care for older persons. AB - Preventive health care for older persons is considered in terms of primary, secondary and tertiary prevention and examples of relevant services are provided both from Canada and from other countries. Three areas of concern are identified, namely communication, quality assurance and funding. It is suggested that various approaches used in other countries, such as Home Visitor Programs, be examined and more generally that comparisons with health care services in other countries be carried out, particularly with respect to evaluations and possible economic steering effects. PMID- 1423114 TI - Edmonton Board of Health celebrates 100 years--or more. PMID- 1423116 TI - Health status of Canadian-born and foreign-born residents. PMID- 1423115 TI - [Characteristics of non-responders to a mental health survey]. PMID- 1423117 TI - Changing patterns of mortality and hospital morbidity among Canadians aged 85 and over. PMID- 1423118 TI - Health promotion through healthy public policy: the contribution of complementary research methods. AB - The focus of the "new public health" is moving from the level of individuals to the level of organizations, communities, and broader social policies. Traditional quantitative methods which are appropriate at the level of individual behaviour change, require adaptation and refinement when sociopolitical change becomes the mechanism for health promotion. Because of their training and experience, health services researchers and health educators, especially psychologists, are understandably resistant to making necessary methodologic changes. Well-designed and carefully conducted qualitative studies, using techniques such as ethnographic interviews, participant observation, case studies, or focus group activities, are required to complement quantitative approaches. These studies can fill gaps where quantitative techniques are suboptimal or even inappropriate. Hard qualitative techniques can also support soft quantitative methods. Their utility in process evaluation is now beyond dispute. Recent work at the New England Research Institute is used to illustrate the role of qualitative research in the evaluation of health promotion through planned sociopolitical change. PMID- 1423119 TI - Health promotion research with heart: keeping a people perspective. PMID- 1423120 TI - Building a methods bridge between public policy analysis and healthy public policy. AB - The literature has only begun to consider what research is needed to support the development and implementation of healthy public policy initiatives. To date, a consistent methodological approach is recommended: multiple methods (document analysis and key informant interviews supplemented by quantitative data) with an aim toward understanding the perspective of key policy stakeholders. Currently, these methods are not the mainstay of policy analysis which is often driven more by a preference for technique (e.g., cost-benefit analysis) than by underlying epistemology or theory. Yet the explicit values of healthy public policy (intersectoral policy-making, public participation, etc.) suggest the importance of paying greater attention to epistemological and theoretical principles when making methodological choices. PMID- 1423121 TI - Learning to 'walk our talk': the implications of sociological theory for research methodologies in health promotion. AB - In recent formulations of the concept of health promotion, such as Achieving Health for All and the Ottawa Charter, emphasis is clearly placed on comprehensivity and the integration of individual and social determinants of health, broadly defined. This paper is premised on the observation that despite evidence of a paradigm shift in the way we talk about health promotion at a conceptual level, we have yet to properly articulate a 'new' research methodology to accompany the 'new' health promotion. The paper has three main sections. First, some of the limitations and contradictions that separate the rhetoric of health promotion from its current operationalization in research practice are discussed. In asserting the inherent links between theory, methodology and method, the need for a new research paradigm is demonstrated. In the second section, seven key issues derived from the literature on sociological theory are identified and discussed in terms of their implications for choosing a new research methodology for health promotion. In the third section it is suggested that using these issue areas as a 'decision map' leads to the selection of a preferred strategy which brings together both interpretive and critical perspectives to bear on our understanding of social reality as it affects health. Elements of both of these approaches and the nature of their potential complimentarity are considered. Throughout these deliberations the reader is encouraged to consider the potentially conservative or activist orientations that alternate methodologies imply, and to critically evaluate how these mesh with the emerging rhetoric of fostering empowerment that is the cornerstone of the 'new' health promotion. PMID- 1423122 TI - Bureaucratic logic in new social movement clothing: the limits of health promotion research. AB - This paper discusses theoretical, methodological and political problems in the field of health promotion research. It argues that these problems result from a partial and contradictory appropriation of the discourse of new social movements. Politically, the health promotion movement is largely confined within the state, rather than the expression of a social movement against the state. The direction of health promotion research and policy is, therefore, caught in the bureaucratic logic of "trapped administrators", and results in contradictory emphases on problems like the development of "health promotion indicators", which show little result in informing a broader but coherent conceptualization of health, let alone in effecting change in health policy and outcomes. Such political problems reflect parallel confusions about theory and methodology. Theoretically, the field relies heavily on a critique of bio-medical science, but fails to move beyond a rhetorical outline of an alternative to systematic arguments about what promotes health. In this regard, the literature on health promotion remains unaware of important conceptual developments in the social sciences, relies on imprecise specifications of major constructs like community empowerment, and has no conception of the state. Methodologically, the literature is influenced by contradictory epistemological tendencies which reflect a positivist inspiration (as in the search for indicators) and an anti-positivist emphasis on agency and social change through the collective action and the discursive reconstitution of social identity, value and meaning. In regard to these questions, this paper is critical of observers who suggest that the way ahead is to embrace post-modern research strategies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423123 TI - Feminist methods in health promotion research. AB - This paper describes and discusses the traditional social scientific approach to health promotion research, details some of its methods of data collection and analysis, outlines some of the principles of feminist methods of research particularly as these provide a critical analysis of traditional methods and concludes with a feminist critique of a typical and influential health promotion document, the Active Health Report (1985). PMID- 1423124 TI - Institutional ethnography: explicating the social organization of professional health practices intending client empowerment. AB - Institutional enthnography uses traditional ethnographic procedures grounded in an analytic approach for explicating the social organization of knowledge. I illustrate the theory and method by describing my experience and analysis-to-date in a study of the social organization of knowledge in mental health, day program occupational therapy in Atlantic Canada. I emphasize the research standpoint within everyday experience. From this point, the researcher explicates (through description) how (micro) social relations, i.e. everyday actions, speech and documentation, are embedded in the (macro) practices of "institutions" such as mental health services. I summarize data management procedures including use of ETHNOGRAPH. Analysis-to-date is showing how the organization of mental health day programs both constrains and creates potential for occupational therapists enabling client empowerment. PMID- 1423125 TI - Fourth generation evaluation, the paradigm revolution and health promotion. AB - The author argues that two events are inextricably linked:first, the increasing disenchantment with the conventional paradigm for conducting science, and second, the changing conceptions of health. With respect to the latter, medical professionals are increasingly moving away from disease as an indicator of health and moving toward conceptions of wellness, and away from a cure model and toward a prevention model. The paper demonstrates what the new inquiry paradigm looks like and what its synergisms are with newer constructions of human health, and finally concludes with additional problems which must be noted. PMID- 1423126 TI - Accessing community development research methodologies. AB - This paper is a perspective on the strengths and weaknesses of community development research offered to health promoters by a community development insider. The author provides her rationale for the opinion that no research paradigm other than the qualitative one satisfies the naturalistic context of either community development or health promotion, including inquiry into concepts such as community health, community wellbeing, community competence and community self-reliance. Attention is drawn to key aspects of the community development process with relevance to health promoters which are largely undertheorized, including clarity about the central issue of the nature of the interaction among learning, action and change. Finally, the paper specifies three implications of the naturalistic paradigm for either research or practice. These include academic prejudice against qualitative research from some quarters, the limitations of all research paradigms for some questions, and essential uncertainties of naturalistic inquiry. PMID- 1423127 TI - Program evaluation within a health promotion framework. AB - Program evaluation can assist in assessing the conceptualization, design, implementation and utility of health promotion action. Evaluation of health promotion, with multiple strategies combining individual, social and policy action, lends itself to an evaluation-as-politics paradigm. Consideration of the interests of all major stakeholders, use of a series of related studies, and a commitment to multiple methods and multiple perspectives characterize this paradigm. Simple, practical research that is adequate for answering relevant questions is required. The program evaluator is not a neutral, scientific observer--he/she is a participant in the political arena along with other stakeholder groups. A model of the areas of interest in evaluation of health promotion, some potential evaluation questions, and a health promotion impact evaluation model are presented to emphasize unique aspects involved in evaluation of health promotion action. The evaluator can take a proactive role and challenge problems in conception and implementation of health promotion action. He/she can advocate for health promotion. PMID- 1423128 TI - A critical perspective on research and knowledge development in health promotion. AB - The paper addresses four issues that pervaded conference deliberations: the relevance of qualitative approaches to research, the importance of community participation in the research process, the need to broaden the disciplinary base of health promotion, and the possibilities for a critical research perspective. The paper suggests why the idea of qualitative methods is so appealing to health promotion researchers, and what may prevent such methods from living up to the expectations held of them. The emphasis on community participation in research expresses an attempt to make research more relevant and accountable, but it also may inhibit the theoretical grounding of research, and create strain between pragmatic and scientific interests. The field of health promotion is inherently multidisciplinary, but it remains unclear if and how different disciplines can be effectively combined or integrated. The relative absence of critical thought at the conference is noted, and the authors argue that a critical perspective is needed in both "research of" and "research for" health promotion. PMID- 1423129 TI - Host resistance and the immune system. AB - Elderly persons are more susceptible and vulnerable to many infections compared with young adults. This phenomenon can be attributed to a decline in host defense mechanisms, particularly altered immune function. The effects of aging on T- and B-lymphocyte function; antigen-presenting cells, natural killer cells, and granulocytes; and organ-specific host resistance are discussed in this article. PMID- 1423130 TI - Infections in elderly persons. An altered clinical presentation. AB - The high prevalence, morbidity, and mortality of infectious diseases in the geriatric population mandates that clinicians caring for older patients become better acquainted and familiar with the special and unique characteristics and features of this common clinical problem. Only through such awareness and understanding will clinical outcomes, functional capacity, and quality of life be improved in the elderly population. PMID- 1423131 TI - Pneumonia. AB - Pneumonia is one of the most serious infections in elderly persons. For example, individuals with nursing-home acquired pneumonia requiring hospitalization have a mortality rate of approximately 40%. In the frail, elderly patient, the clinical manifestations may be very nonspecific and consist only of confusion and falls; these individuals often may not present with either fever or cough. Sputum is frequently not available for culture in this population, and chest radiography for pneumonia may be confounded by underlying pulmonary or cardiac disease. Antibiotic therapy for pneumonia in older patients must often be empirical. PMID- 1423132 TI - Vaccinations. AB - Tetanus-diphtheria toxoid, influenza virus vaccines, and pneumococcal vaccine are recommended for older persons in the United States by the Centers for Disease Control. But most high-risk older persons remain unvaccinated, despite experiencing relatively high rates of tetanus, influenza-related complications, and pneumococcal disease, and having available effective, safe, and low-cost vaccines. Strategies for improving these vaccination rates require an intensive approach focused on (1) identifying older persons with high-risk conditions, (2) improving the delivery of vaccines, (3) improving the acceptance of vaccines by older persons, and (4) establishing mandatory immunization programs. PMID- 1423133 TI - Tuberculosis. AB - In the United States, the incidence of tuberculosis (TB) is higher in elderly persons than in any other segment of the population, except in HIV-infected persons. The diagnosis of TB, however, is all too often not considered in geriatric patients. Although elderly nursing home residents are at a greater risk for TB than the aging population in the community setting, the majority (80%) of active TB cases in elderly persons occur in community dwellers. The diagnosis, treatment, and prevention of TB are reviewed in this article. PMID- 1423134 TI - Fungal infections. AB - Increased travel and outdoor leisure activities place the elderly individual at risk for infection with the endemic mycoses, histoplasmosis, blastomycosis, coccidioidomycoses, and sporotrichosis. Elderly patients who are immunosuppressed are at risk for infection with the opportunistic fungi such as Candida and Aspergillus. In this article, the clinical manifestations and the approach to diagnosis are discussed. The use of antifungal agents that are currently available to treat severe fungal infections also are reviewed. PMID- 1423135 TI - Urinary tract infection. AB - Urinary tract infections are the most common bacterial infections experienced by elderly patients. These infections are often asymptomatic, although on occasion they produce discomfort for selective older patients (particularly those with obstructive uropathy), and present a risk for bacteremia, septic shock, adult respiratory distress syndrome, and death. The limited available data suggest that there are major differences with regard to pathogenesis, microbiology, clinical features, laboratory abnormalities, and therapy between young and elderly women who develop symptomatic pyelonephritis. There is a need to provide a standard antibiotic prophylaxis program to those elderly patients with specific cardiac conditions who are scheduled to undergo urinary procedures. PMID- 1423136 TI - Catheter-associated bacteriuria. AB - Catheter-associated bacteriuria is the most common nosocomial infection in both acute and long-term care facilities. Complications include fever, bacteremia, acute pyelonephritis, urinary stones, chronic renal inflammation, and death. Catheter-associated bacteriuria can be postponed by maintaining the closed nature of the catheter system. Postponement may become prevention of bacteriuria if the catheter is removed as soon as possible. PMID- 1423137 TI - Infections in the nursing home. AB - Infections are a common cause of morbidity and mortality in nursing home patients. A variety of factors predispose these patients to infections. Infections commonly encountered among these patients include pneumonia, urinary tract infections, tuberculosis, and gastrointestinal and skin infections. Preventive measures and infection control techniques offer protection to both patients and employees. PMID- 1423138 TI - Infected pressure and diabetic ulcers. AB - Infected pressure and diabetic ulcers are encountered frequently by clinicians caring for the geriatric population. These infections are polymicrobial and are often complicated by sepsis syndrome and osteomyelitis. Together, these infections account for significant morbidity and mortality in elderly persons. A team approach to management is essential for the clinician, and efforts should focus primarily on prevention. PMID- 1423140 TI - Peritonitis. AB - Intraperitoneal infections or inflammatory disease in elderly patients are a diagnostic challenge that will be encountered with increasing frequency in the aging population of the United States. Diagnostic clues are not overt and frequently appear late in the course of the disease. Confusion and subtle changes in clinical status are important signals. A high index of suspicion is required to initiate diagnostic procedures. Therapy will frequently be modified not only to the disease process but also to the patient to incorporate concepts of minimally invasive procedures. The advent of laparoscopic surgery may be a great advance in the diagnosis and treatment of intra-abdominal crisis in geriatric patients. It also may make elective surgery conform more to the goals of the geriatric patient and thus prevent the high morbidity and mortality associated with emergency surgery in this age group. PMID- 1423139 TI - Methicillin-resistant Staphylococcus aureus infection. AB - Elderly patients with chronic illnesses are at increased risk of becoming colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA). Therapeutic choices for the treatment of MRSA have been limited by the ever expanding resistance of organisms and drug toxicity. In hospitals, the MRSA carrier state has been associated with increased risk of infection and possible dissemination of the organism to other patients. The epidemiology of MRSA and its significance in long-term care have been less well defined. Isolation procedures and steps to contain or eradicate MRSA should be accommodated to the individual needs of the facility and its resources. PMID- 1423141 TI - Bacterial meningitis. AB - Meningitis remains a significant health problem for the older adult population. Although the overall incidence of this disease has decreased in the United States, the incidence of meningitis in the elderly population is increasing. Additionally, the recognition of meningitis in the older adult may be more difficult because the usual symptoms and signs are neither as specific nor as sensitive as they are in a younger population. Newer antibiotics have provided better therapeutic approaches to some of the organisms responsible for this disease, and newer methods of therapy beyond antibiotics hold the promise of altering the unacceptably high morbidity and mortality. PMID- 1423142 TI - Infective endocarditis. AB - This article examines the presentation, diagnosis, and treatment of infective endocarditis in elderly persons. Special problems that cause complications and mortality to be higher in older patients than younger patients also are discussed. Areas of active debate and research are mentioned, including the use of diagnostic echocardiography, treatment of specific bacterial species, sources of iatrogenic endocarditis, and antibiotic prophylaxis. PMID- 1423143 TI - Sepsis. AB - Septic shock is associated with a very high mortality in elderly patients. This is likely due to the age-related anatomic and physiologic changes and the presence of comorbid diseases. Medical management of patients with septic shock consists of antibiotics, fluids, vasopressors, and careful monitoring. Judicious use of antiendotoxin monoclonal antibodies may be a beneficial adjunctive therapy. PMID- 1423145 TI - Guidelines for the evaluation and management of family violence. PMID- 1423144 TI - Antimicrobial therapy. AB - Antibiotic dosing is not influenced by age as much as by the weight loss and loss of renal function that occurs with advanced age. The chronic diseases that afflict the frail, elderly person, however, exert a profound influence on the types of infections and the variety of organisms that must be considered in empiric therapy choices. Safety, efficacy, and cost favor the choice of broad spectrum oral antimicrobials or the newer quinolones for initial treatment of moderately severe, urinary, respiratory, or skin and soft-tissue infections. When parenteral empiric therapy is needed, the third-generation cephalosporins are preferable to multi-drug or narrow-spectrum regimens. To avoid adverse reactions, the frail, elderly patient generally should be given somewhat lower doses at longer dose intervals compared with younger patients. PMID- 1423146 TI - Clozapine in the treatment of refractory schizophrenia: Canadian policies and clinical guidelines. AB - Clozapine is an atypical neuroleptic agent that has recently become available in Canada with potential clinical efficacy in the treatment of refractory schizophrenia, and in patients with schizophrenia neurologically intolerant to conventional neuroleptics. Although it causes few extra-pyramidal symptoms, the drug has a number of other adverse effects including a risk of agranulocytosis in one to two percent of all patients. Because of this, the use of the drug is permitted only if the white blood count is monitored weekly. The monitoring system, outlined in this article, requires a coordinated effort between clinical staff, pharmacy, laboratory and the Clozaril Support and Assistance Network. Clinical guidelines are proposed, detailing the indications and contraindications for treatment and the pharmacokinetics, dosing, adverse effects, and drug interactions with clozapine. In addition, the economics, government policies and implications for future research are considered. Although there are administrative and clinical difficulties associated with its use, clozapine represents an advance in therapeutic research. Patients and family members will be inquiring about the drug and may deserve a trial. This article aims to inform Canadian mental health professionals about the safe and beneficial use of clozapine. PMID- 1423147 TI - Victims of violence: aspects of the "victim-to-patient" process in women. AB - This paper is an overview of aspects of the victim-to-patient process which reflects the interrelationship between mental health and mental disorder, particularly of women who suffer the sexual assault, sexual abuse, or wife assault. Knowledge of the psychological processes and symptoms aids diagnosis, modifies treatment and the process of recovery following acts of violence. PMID- 1423148 TI - [Dysmorphophobia (body dysmorphic disorder)]. AB - This article reviews the historical and terminological origins of dysmorphophobia from Herodotus to today. It explains the differences pointed out by many authors, including the DSM-III-R, between body dismorphic disorder and delusional disorder somatic type, which are referred to as monosymptomatic hypochondriacal psychoses in Europe. Epidemiological data, clinical characteristics and outcome are discussed. Explicative theories and neurobiological, developmental and analytical aspects of body image are presented. The association between body dismorphic disorder and other disorders is analyzed, and treatment possibilities are discussed. The authors suggest that body dismorphic disorder be classified with obsessive compulsive disorder, whatever the intensity of symptomatology, rather than with somatoform or delusional disorder, and treated with serotonin uptake inhibitors or neureptics that have been proven to be effective for the treatment of this disorder, such as pimozide. PMID- 1423149 TI - Social risk factors for borderline personality disorder: a review and hypothesis. AB - A number of behaviours associated with borderline personality disorder (including attempted suicide, suicide, substance abuse, and antisocial behaviour) are on the increase among the young. The common factor in these disorders is impulsiveness. Evidence is reviewed suggesting that social disintegration reduces the threshold of impulsive behaviours. It is proposed that this is the mechanism through which social risk factors effect the prevalence and morbidity of borderline personality. A number of ways of testing this hypothesis are suggested. PMID- 1423150 TI - Correlates of sexual abuse in women with anorexia nervosa and bulimia nervosa. AB - Of 184 female outpatients meeting the DSM-III-R criteria, for anorexia nervosa, bulimia nervosa, or anorexia nervosa with bulimia, approximately 25% reported previous sexual abuse. Furthermore, previous sexual abuse was associated with greater psychological disturbance, measured by the Eating Disorder Inventory and Eating Attitudes Test. Sexual functioning did not differ among women who did or did not report sexual abuse. This finding suggests that sexual abuse or its correlates may affect severity rather than type of eating disorder. PMID- 1423151 TI - Intravenous clomipramine for OCD. PMID- 1423152 TI - Psychiatric services: a survey of nursing homes and homes for the aged in Ontario. AB - A survey was conducted to determine perceptions and attitudes of psychiatric services available to nursing homes and homes for the aged across Ontario. A questionnaire was sent by mail to medical and nursing directors separately. Thirty-six point eight percent of responders reported that the nursing home residents never receive psychiatric care, and 88.2% of responders estimated the total psychiatric care received by all of their residents per month was five hours or less. Almost three-quarters of the responders stated that they require more psychiatric services. Significantly more nursing directors than medical directors wanted more psychiatric services. Southwestern Ontario, followed by Northern Ontario, had the least perceived availability of a visiting psychiatrist. Perceived availability was greatest in larger urban areas and least in rural areas. The mean percentage of residents perceived to have psychiatric or behavioural problems was 30.5%, while the mean percentage perceived to require psychotropic medication was 37.4%. Physical aggression, wandering and agitation were identified as the behavioural problems of greatest concern to staff. When a visiting psychiatrist is not available, residents sometimes have to travel long distances for psychiatric evaluation. Planning is required to facilitate and encourage the development of efficient and effective psychiatric services for long term care facilities for the elderly. PMID- 1423153 TI - Assessing the "criminalization" of the mentally ill in Canada. AB - This paper is an overview of the conceptual and methodological problems encountered trying to assess the hypothesis that the mentally ill, as a consequence of deinstitutionalization, are being "criminalized". Generalizations are difficult to make, in large part because most of the studies are American and do not fit well into the Canadian scene. Relevant Canadian findings are reviewed and compared to the US data. There is some evidence that Canadian patients may be diverted from the criminal justice system more often than in the US, where there are fewer resources. However, this conclusion must be tempered by the fact that Canadian surveys have found high rates of mental disorder among prison and jail inmates. PMID- 1423154 TI - Depression and level of functioning in patients with rheumatoid arthritis. AB - This study examined the degree to which depression is related to physical and psychosocial dysfunction. The Beck Depression Inventory and the Sickness Impact Profile were administered to 34 patients with rheumatoid arthritis. Information on the demographic variables (age and employment status) and medical status variables (duration of disease and functional classification) were collected for each patient. Regression analyses revealed that depression was an important predictor of total, physical and psychosocial sickness-related behavioural dysfunction. The proportion of variance attributed to depression was moderate to large and was significant even after controlling for important demographic and medical status variables. These results suggest that depression is an important factor to be considered when evaluating the clinical significance of physical and psychosocial dysfunction in patients with rheumatoid arthritis. PMID- 1423155 TI - Adult children of alcoholics in treatment programs for anxiety disorders and substance abuse. AB - Studies of the first-degree relatives of patients with alcoholism and anxiety disorders have identified a significant overlap of these disorders. Forty percent of the patients in an outpatient anxiety disorder program were adult children of alcoholics (ACOA), a proportion similar to that found in the substance abuse program. The ACOAs in both programs were younger, had higher co-dependency scores and were younger when they had their first psychiatric contact than the controls. The adult children of alcoholics who had anxiety disorders were more likely to be female and their alcoholic parents were less likely to have had psychiatric antecedents to alcoholism. Aside from substance abuse, similarities in sociodemographic variables and the impact of the parents' alcoholism were noted, reinforcing the hypothesis that vulnerabilities to anxiety disorders and alcoholism overlap. PMID- 1423156 TI - Intensive early exposure to geriatric psychiatry in residency training: impact on career choice and practice. AB - The authors examined the impact of intensive early exposure to geriatric psychiatry on the career choice of trainees. All psychiatrists who had completed a six month inpatient rotation on a general hospital psychogeriatric unit as part of their first year of residency were interviewed three to 12 years later with a questionnaire designed to elicit practice patterns, prior interest in geriatrics, and the major influences of the rotation. Nine of 16 trainees had spent more than 50% of their time since graduation treating elderly patients. Those surveyed who were not practicing geriatrics spontaneously reported positive influences of the rotation on psychiatry training in general. The nature of geriatric psychiatry and the clinical issues, as well as the supervisors and educational activities were rated as the most important influences of the rotation. Early experience in psychogeriatrics seems valuable for subspecialty recruitment as well as general psychiatry training. PMID- 1423157 TI - [Community services and quality of life: a study of the impact in a remote region]. AB - This longitudinal study with a matched comparison group was conducted in Abitibi, an area in North-West Quebec. Its goal was to observe the impact of community support services on the quality of life of long term psychiatric patients living in a remote area. A cohort of 47 subjects, living in a small town with a comprehensive network of community support services, was compared with a similar group living in a neighbouring city with only outpatient services. The satisfaction with life domains scale developed by Andrews and Withey and adapted by Baker and Intagliata was used at four times during the study. According to the results, the subjective perception of the quality of life in the two groups is comparable, even though the objective conditions are less favorable for the group participating in the community support program. The highest ratings were given to the place of residence, the neighborhood and its commodities; the lowest ratings were given to their love life and financial situation. One can observe a stability of the measures of quality of life over time and for the two groups. The perceptions of the sample living in a remote area are much more favorable than the ones of a comparable group living in the Montreal area. These results are discussed in a double perspective: the role of community support services in the daily life of people who are having severe and persistent problems of mental health, and the interest of measures of quality of life. PMID- 1423158 TI - A treatment approach for patients in midlife. AB - A treatment concept is described based on phase of life developmental theory for certain middle-aged patients encountered in a general hospital setting that--of a midlife crisis unit. Theoretical considerations on the rationale for setting up a midlife crisis unit, a brief description of a pilot unit of this nature during its first year of operation and several clinical vignettes illustrating typical presenting situations are discussed. PMID- 1423159 TI - The management of a case of treatment-resistant paraphilia with a long-acting LHRH agonist. AB - A patient with multiple paraphilias who had been treated for several years with sex drive reducing agents (cyproterone acetate and medroxyprogesterone acetate) with little effect on sexual activity or fantasy was offered treatment with long acting leuprolide acetate, on LHRH agonist. This produced a marked decrease in all reported sexual thoughts and activities with no significant side-effects. PMID- 1423161 TI - Evolving misidentification syndromes and facial recognition deficits. AB - In this paper, the authors report the case of a 33 year old man with several misidentification delusions involving the self. Evidence suggests that one type of misidentification delusion may evolve into another type. Neuropsychological testing further suggests that misidentification delusions may be associated with subtle abnormalities in facial recognition abilities and with non dominant cerebral compromise. PMID- 1423160 TI - Are too many children being treated with methylphenidate? AB - A survey was conducted of the use of methylphenidate in British Columbia during a six month period to determine if a disproportionate number of children are being treated with methylphenidate for hyperactivity. The data obtained do not indicate a problem regarding the diagnosis of attention deficit hyperactivity disorder in children. However, the data pertaining to adults indicate that the reasons stated for prescribing methylphenidate are controversial in a significant number of cases. PMID- 1423162 TI - Post-traumatic stress disorder: an overview. AB - An overview of post-traumatic stress disorder, including a brief historical survey, and its epidemiology, nosology, etiology, clinical presentation, treatment, prognosis as well as a short vignette, highlights the fact that this disorder prevails in times of war and peace. Early intervention is emphasized as the key to successful treatment. The timeliness for Canadian mental health professionals to review this disorder is also mentioned. PMID- 1423163 TI - Augmentation of valproate with lithium in a case of rapid cycling affective disorder. AB - Rapid cycling affective disorder is characteristically unresponsive to conventional interventions. In bipolar rapid cycling affective disorder, the manic episodes may be controlled with either neuroleptics or electroconvulsive therapy, but the depressive episodes are highly intractable. This report describes the successful treatment of a patient with a bipolar rapid cycling affective disorder using a combination of valproic acid and lithium carbonate. PMID- 1423164 TI - Clinical experience with valproic acid in 22 patients with refractory bipolar mood disorder. PMID- 1423165 TI - Interaction of fluoxetine and chloral hydrate. PMID- 1423166 TI - What is behaviour therapy? PMID- 1423167 TI - Antidepressants: which to use first? PMID- 1423168 TI - Computerized screening interviews. PMID- 1423170 TI - Long-term treatment results of postoperative radiation therapy for advanced stage oropharyngeal carcinoma. AB - BACKGROUND: The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center. METHODS: Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%). RESULTS: The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions. CONCLUSIONS: The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery. PMID- 1423169 TI - Significance of glutathione S-transferase-pi as a tumor marker in patients with oral cancer. AB - BACKGROUND: The authors analyzed the clinical usefulness of glutathione-S transferase-pi (GST-pi) as a tumor marker in patients with oral cancer. METHODS: GST-pi levels in plasma of 61 patients with oral squamous cell carcinomas, 65 patients with benign oral diseases, and 78 healthy subjects were investigated with the sandwich enzyme-immunoassay (EIA) system. RESULTS: Elevated GST-pi levels in plasma were observed in patients with oral cancer, but patients with benign oral diseases had normal GST-pi levels. More than 70% of patients with Stage III or IV oral cancer and more than 50% of those with Stage I and II disease had elevated levels of GST-pi in plasma. Elevated levels of GST-pi in plasma were also discovered in most patients with tumor recurring after surgery before recurrence was detected clinically. GST-pi also was found to be a useful marker for evaluating the response to chemotherapy, for monitoring postoperative tumor resectability or tumor burden, and for predicting the recurrence of tumor in patients with oral cancer. CONCLUSIONS: GST-pi is considered to be a useful aid for early diagnosis, predicting tumor extent, and determining parameters of treatment efficacy and prognosis for oral cancer. PMID- 1423171 TI - Auditory brain stem responses in patients after radiation therapy for nasopharyngeal carcinoma. AB - BACKGROUND: The study evaluated the incidence and severity of brain stem myelopathy occurring after radiation exposure in a cohort of patients who received external radiation exposure for nasopharyngeal carcinoma (NPC). METHODS: Brain stem function was investigated by auditory brain stem responses (ABR). RESULTS: Four of 21 patients who could be examined had aberrations in ABR. Three patients showed highly abnormal ABR, with no distinctive patterns or peaks. Two of these patients also showed clinical symptoms of brain stem dysfunction, including multiple palsies in cranial and peripheral nerves, whereas the third patient had no clinical signs of brain stem disorders. The fourth patient had minor conduction delays in ABR. The remaining group of 17 patients who could be examined had ABR latency and transmission times similar to those of the control group. None of these patients had neurologic symptoms. Dose-response analysis showed that patients who received radiation doses of 59 Gy or less to the brain stem had normal ABR, whereas four of six patients who received a dose of 68 Gy had manifest or subclinical brain stem dysfunction. CONCLUSIONS: The results emphasize the importance of protecting the brain stem from high-dose radiation when possible. The results also demonstrate the usefulness of ABR as a supplement to the clinical examination of patients with possible myelopathy occurring after radiation exposure. PMID- 1423172 TI - Bone infarct-associated osteosarcoma. AB - Reported is a patient with an osteosarcoma arising in a medullary infarct of the humerus. Infarct-associated sarcoma (IAS) of bone is rare. In a collective review of 50 cases reported in the medical literature, only 37 were fully documented. Including our patient, 26 men and 12 women, ranging in age from 18 to 82 years (mean, 53.4 years) have been reported. Black patients appeared to be disproportionately represented, accounting for 36% of the group. In most patients, there was no known cause for the infarct, whereas in the remainder, the most common underlying condition was a prior dysbaric event or alcoholism. Approximately 75% of the patients had multiple bone infarcts. The femur was involved in 21 patients, the tibia in 14, the humerus in 2, and the radius in 1. Among 40 sarcomas in these patients, 7 (18.4%) were osteosarcomas, and 29 (72.5%) were malignant fibrous histiocytomas. The survival rate in patients with IAS is poor: 5 of the 7 patients with osteosarcoma (71%) and 20 of the 31 other patients (65%) died of tumor. Eight patients are alive and well, all for longer than 5 years. PMID- 1423173 TI - The association of erythrocytosis and chronic lymphocytic leukemia. AB - The authors report the clinical course of three patients with well-documented chronic lymphocytic leukemia (CLL) and concomitant erythrocytosis. Associated disorders included immune cytopenias, Hashimoto struma and Richter syndrome. Durable complete remissions of CLL have occurred in two patients. Inasmuch as a chance association of these two relatively rare hematologic disorders is unlikely, the available information suggests that a pluripotent stem cell with the capacity to differentiate into lymphoid and erythroid pathways is the most attractive hypothesis. PMID- 1423174 TI - Molecular genetic, cytogenetic, and immunohistochemical characterization of alveolar soft-part sarcoma. Implications for cell of origin. AB - BACKGROUND: Alveolar soft-part sarcoma is a rare tumor of uncertain histogenesis. METHODS: The authors report a patient who was studied using immunohistochemistry, cytogenetic analysis, and molecular probes for MyoD1 and MYCN (N-myc proto oncogene). RESULTS: By immunoperoxidase, the tumor was focally positive for vimentin, neuron-specific enolase, and S-100 protein but negative for muscle specific actin, desmin, and low-molecular-weight keratin. Direct chromosome analysis of primary tumor cells using G-banded preparations yielded two clonally abnormal lines: one demonstrated trisomy 47,XX+5; the other demonstrated 46,XX,1p ,17q+. Expression of the MYCN RNA was detectable at a low level, and MYCN was single copy at the DNA level. Expression of the myogenic molecular marker MyoD1 was not detected by Northern blotting analysis. CONCLUSIONS: This is the first detailed study to address the molecular biology and tumor cytogenetics of alveolar soft-part sarcoma. The results of this study indicate a neurogenic origin for this unusual tumor and fail to provide support for the notion of a myogenic origin. PMID- 1423176 TI - Treatment plans for black and white women with stage II node-positive breast cancer. The National Cancer Institute Black/White Cancer Survival Study experience. AB - BACKGROUND: The National Cancer Institute Black/White Cancer Survival Study began patient accrual in 1985 and was designed to investigate factors that might contribute to the observed racial differences in survival for cancer of the breast, uterine corpus, colon, and bladder. METHODS: To determine whether there were racial differences in treatment in a clinically homogeneous set of patients, 305 (25%) of the 1222 women in this study with Stage II node-positive (N+) breast cancer were evaluated. RESULTS: Patient characteristics for blacks and whites were similar for age, metropolitan area of residence, tumor size, extent of nodal involvement, and steroid receptors. Differences in histologic findings, tumor grade, and nuclear atypia were observed. Blacks had a higher frequency of comorbid conditions, especially hypertension (P < 0.00001). Fewer blacks underwent breast-conserving surgery (P = 0.004). In a multivariate analysis, race was no longer a significant factor in the selection of primary treatment, but education and metropolitan area of residence remained significant. Blacks and whites received similar postoperative systemic therapy, with combination chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and tamoxifen, the most common cytotoxic and endocrine therapies used. CONCLUSIONS: The National Cancer Institute consensus statement concerning adjuvant therapy for breast cancer was published in the middle of the 2-year period that study cases were accrued, and treatment plans in this study generally agreed with consensus guidelines. Should survival differences in black and white patients with Stage II N+ disease in this study be found, they are unlikely to be attributable to differences in initial or postoperative treatment. PMID- 1423175 TI - Primary non-Hodgkin malignant lymphoma of the breast. An immunohistochemical study of seven patients and literature review of 152 patients with breast lymphoma in Japan. AB - BACKGROUND: The breast is rarely a primary site for extranodal malignant lymphoma. Most reported primary non-Hodgkin malignant lymphomas of the breast (PBL) are of B-cell phenotype. METHODS: Histologic and immunohistochemical analyses of seven patients with PBL and a statistical analysis of 152 patients with PBL reported in the Japanese literature were performed. RESULTS: Malignant lymphoma could not be predicted preoperatively with clinical and radiologic findings; breast carcinoma, fibroadenoma, and phyllodes tumor were the preoperative diagnoses. All patients were women; they ranged in age from 31 to 80 years (mean, 57.6 years). The right breast was involved initially in five patients. In four, only the breast was involved (Stage I), whereas in three, the ipsilateral axillary lymph nodes (Stage II) were involved at diagnosis. According to the Working Formulation, all patients belonged to the intermediate grade and were classified as having diffuse large cell (five patients) or mixed (two patients) lymphoma. Immunophenotypic analysis revealed that all patients had B cell lymphoma. No patients had lymphoepithelial lesions, which is the characteristic feature in categorizing a lymphoma as a mucosa-associated lymphoid tissue (MALT) lymphoma. A statistical analysis of the patient reported in the Japanese literature has divided PBL into two types: a bilateral type that affects younger women and a unilateral type that has a broad age distribution, but preponderantly occurs in older women. The age and stage at diagnosis were significant prognostic factors in predicting the survival time, but the location and size of the tumor at initial presentation, histopathologic type, terminal leukemic manifestation, and treatment modality were not. CONCLUSIONS: This study indicates that most PBL are diffuse large cell lymphoma of B-cell phenotype and that the age and stage at diagnosis are significant prognostic factors. PMID- 1423177 TI - Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-Year results from the Nishi-Nippon Group of the Adjuvant Chemoendocrine Therapy for Breast Cancer Organization. AB - BACKGROUND: A randomized adjuvant trial was conducted from October 1982 to January 1985 to evaluate the addition of tamoxifen (TAM) to combination chemotherapy with perioperative mitomycin C (MMC) and ftorafur (FT) for patients with estrogen receptor (ER)-positive tumors and the addition of PSK, a biologic response modifier, to MMC+FT chemotherapy for patients with ER-negative tumors in operable Stage IIA, IIB, and IIIA cancer. The doses used were 20 mg of oral TAM daily, 600 mg of oral FT daily, and 3 g of oral PSK daily for 2 years. Intravenous MMC (13 mg/m2) was given on the day of operation. METHODS: A total of 967 patients were entered and randomized by stratification based on ER status and staging (1978 International Union Against Cancer [UICC] criteria at the time of trial execution). Of 967 patients, 914 (94.5%) were evaluable. At 5-year follow up, significant prolonged overall survival (OS) and relapse-free survival (RFS) times were seen with the addition of TAM in patients with ER-positive and Stage IIIA T3N0 cancer (1987 UICC-American Joint Committee on Cancer [AJCC] criteria); however, no significant survival benefit from TAM was seen in patients with ER positive and Stage IIA T2N1 cancer. There was no significant difference between regimens, with or without PSK, in patients with ER-negative disease. RESULTS: Results of subset analyses suggested a benefit from TAM in postmenopausal patients with ER-positive and Stage IIA T2N1 cancer and a benefit from PSK in patients with node-negative, ER-negative, and Stage IIA T2N1 cancer. CONCLUSIONS: The 5-year results of the current trial showed a survival advantage by the addition of TAM to chemotherapy in patients with ER-positive and Stage IIIA T3N0 cancer. PMID- 1423178 TI - Phase III trial of cyclophosphamide versus cyclophosphamide, doxorubicin, and methotrexate in hormone-refractory prostatic cancer. A Hoosier Oncology Group study. AB - BACKGROUND: Between August 1984 and November 1989, the Hoosier Oncology Group conducted a Phase III study comparing cyclophosphamide (CTX) with cyclophosphamide, doxorubicin, and methotrexate (CAM) in patients with hormone refractory metastatic prostatic cancer to determine whether the addition of doxorubicin and methotrexate to the cyclophosphamide regimen conferred any survival advantage. METHODS: One hundred three patients were registered and randomized, 99 were evaluable for response, and all were evaluable for survival results. All had histologically confirmed metastatic prostatic cancer and had not responded to hormonal therapy. Fifty-three patients received CTX alone, and 50 received CAM. Seventy-one patients (69%) had evaluable disease, and 32 (31%) had measurable disease. RESULTS: There were no complete responses and only four (13%) partial responses in the patients with measurable disease. There was no difference in overall survival time between the two treatment arms in either patients with a Karnofsky performance status (KPS) of 80-100 (median survival, 9.0 versus 9.5 months; P = 0.93) or in those with a KPS of 50-70 (median survival, 5.0 versus 6.0 months; P = 0.51). There was no difference in overall time to progression between the two treatment arms (median time to progression; 4.4 versus 6.2 months; P = 0.07). Toxicity was tolerable in both regimens. CONCLUSIONS: It was concluded that there was no survival advantage to CAM over CTX alone. New chemotherapeutic agents with greater activity against prostatic cancer must be identified. PMID- 1423179 TI - Lipid-associated sialic acid, squamous cell carcinoma antigen, carcinoembryonic antigen, and lactic dehydrogenase levels as tumor markers in squamous cell carcinoma of the head and neck. AB - BACKGROUND: Circulating tumor markers are valuable adjuncts in the management of several malignant lesions, including germ cell tumors and adenocarcinomas of the breast, colon, prostate, and ovary. However (to the authors' knowledge), currently, no serologic markers have been shown to have prognostic value for patients with squamous cell carcinomas of the head and neck (SCCHN). METHODS: Novel and existing markers were evaluated prospectively in patients with SCCHN: The levels of lipid-associated sialic acids (LASA), squamous cell carcinoma circulating antigen (SCC-Ag), carcinoembryonic antigen (CEA), and lactic dehydrogenase (LDH) were evaluated in 52 patients: 42 with active measurable SCCHN and 10 with no clinical evidence of active disease after treatment (NED). RESULTS: In patients with active disease, LASA, SCC-Ag, CEA, and LDH were elevated in 71%, 33%, 27%, and 18%, respectively, and in seven patients with distant metastasis (M1) in 100%, 86%, 57%, and 33%, respectively. None of the markers were elevated in the NED group. The incidence and magnitude of LASA and SCC-Ag elevations correlated with the extent of disease (active disease versus NED, Stage III versus IV, T0-3 versus T4 primary lesions, M0 versus M1). LDH and CEA elevations correlated primarily with the presence of distant metastases. CONCLUSIONS: LASA appears to be a promising sensitive marker of SCCHN, followed in decreasing order of sensitivity by SCC-Ag, CEA, and LDH. Additional study to evaluate the specificity of LASA and its correlation with tumor response to therapy is warranted. PMID- 1423180 TI - "Locked-in syndrome" after intrathecal cytosine arabinoside therapy for malignant immunoblastic lymphoma. AB - A 22-year-old man with malignant immunoblastic lymphoma had "locked-in" syndrome within 48 hours of receiving a single (100 mg) dose of intrathecal cytosine arabinoside (ara-C) in conjunction with intravenous ara-C, cisplatin, and doxorubicin. Eight hours after therapy, the patient had central hypoventilation and blurred vision that progressed to blindness within 3 hours. During the next 10 hours, he became completely quadriplegic but remained intermittently alert and was able to respond to commands by eye or head movements. Radiographic studies showed necrosis of the medulla and swelling of the entire spinal cord. The patient persisted in a locked-in state until his death 3 weeks later, after removal of life support systems. Autopsy confirmed extensive necrosis of the lower medulla, optic chiasm, cranial nerves I and IV, and spinal cord. This case was unusual for its severity. The temporal relationship to ara-C instillation favors a toxic idiosyncratic response to chemotherapy. The authors advocate caution when bolus intrathecal and intravenous ara-C are administered to a patient within a short time of each other. PMID- 1423181 TI - Phase III double-blind comparison of intravenous ondansetron and metoclopramide as antiemetic therapy for patients receiving multiple-day cisplatin-based chemotherapy. AB - BACKGROUND: Ondansetron hydrochloride is a selective serotonin subtype 3 (5HT3) receptor antagonist that has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. METHODS: This double-blind study compared the safety and efficacy of intravenous ondansetron with metoclopramide in patients receiving a 4- or 5-day regimen of cisplatin (20-40 mg/m2/day) combination chemotherapy. Forty-five patients were enrolled, and efficacy of the drug therapy could be studied for all 45. Patients were randomly assigned (1:1) to receive three daily intravenous doses of either 0.15 mg/kg ondansetron or 1 mg/kg metoclopramide. All patients were monitored daily for the number of emetic episodes (vomiting or retching), severity of nausea, adverse events, and laboratory safety parameters. RESULTS: Seven (30%) patients who received ondansetron had no emetic episodes throughout the entire study period compared with two (9%) who received metoclopramide (P = 0.077). The greatest difference in antiemetic efficacy was seen on day 1, when 18 (78%) patients who received ondansetron had no emetic episodes compared with 3 (14%) patients who received metoclopramide (P < 0.001). Significantly fewer antiemetic treatment failures (more than five emetic episodes or withdrawal from the study) occurred with patients given ondansetron (9%) than with those given metoclopramide (50%) during the entire study period (P = 0.002). The most commonly reported adverse event associated with ondansetron therapy was headache (controlled with acetaminophen), whereas diarrhea and restlessness were the most commonly reported adverse events associated with metoclopramide therapy. Extrapyramidal symptoms were judged to have occurred in 13 patients who received metoclopramide and 1 patient who received ondansetron. However, the patient who received ondansetron subsequently was judged to have had an anxiety attack. In patients with low or normal baseline transaminase values, a greater percentage who received ondansetron had transient increases as great as twice the upper limit of normal in aspartate transaminase (5% versus 0%) and alanine transaminase (17% versus 6%) than those who received metoclopramide. CONCLUSIONS: Ondansetron is superior to metoclopramide as antiemetic therapy for multiple-day cisplatin-based chemotherapy. PMID- 1423182 TI - Granulocyte-macrophage colony-stimulating factor. Preliminary observations on the influences of dose, schedule, and route of administration in patients receiving cyclophosphamide and carboplatin. AB - BACKGROUND: In an attempt to learn how best to administer granulocyte-macrophage colony-stimulating factor (GMCSF), the authors performed a Phase I study of this agent. They were interested in the influences of dose, schedule, and route of administration on the effects of GMCSF in patients receiving standardized 1-day regimens of cyclophosphamide (CYCLO) and carboplatin (CBDCA). METHODS: Between June 1988 and March 1991, 57 patients with advanced cancer received GMCSF in association with CYCLO 1 g/m2 plus CBDCA 225-700 mg/m2. After the first dose escalation to 300 mg/m2 of CBDCA, patients who had previously received chemotherapy or radiation therapy were excluded. GMCSF was administered in three different doses, five different schedules, and by two different routes. Altogether, 17 different treatment groups were observed. In addition, 24-hour GMCSF serum concentration curves were charted in four patients. RESULTS: Using four sequential groups of three patients each who had received myelosuppressive treatment, treatment with CYCLO 1 g/m2 and CBDCA 225 mg/m2, the apparent superiority of daily subcutaneous injection over 30-minute daily IV infusion of GMCSF was demonstrated graphically. Subsequently, the authors observed apparent enhancement of GMCSF effects beyond those produced by the initially selected 20 day basic 10 micrograms/kg daily SC regimen beginning 2 days after chemotherapy. When administered SC every 12 hours for 14 days beginning the day after chemotherapy, GMCSF appeared to ameliorate the severity of both leukopenia and thrombocytopenia. These effects permitted escalation of the CBDCA dose to 700 mg/m2 (with 1 g/m2 of CYCLO) before cytotoxic tolerance limits were reached. Graphic small group comparisons suggest that GMCSF given SC in doses of 5 micrograms/kg twice daily may produce comparable leukocyte and platelet support after chemotherapy with lower toxicity than occurs from higher doses. Prechemotherapy priming with GMCSF twice daily for an additional 4 days (days -6 to -3) seems to ameliorate postchemotherapy cytopenias further but at the cose of some increased risk of GMCSF toxicity. Although most of the toxic effects of moderate-dose GMCSF are controlled by antihistamines and ibuprofen, oral glucocorticoids (e.g., prednisone, 10 mg twice daily during the second week of GMCSF administration) may be required in patients with serositis, pulmonary infiltrates, or severe skin eruptions. CONCLUSIONS: Our observations suggest that GMCSF should be administered SC in doses of approximately 5 micrograms/kg every 12 hours for 10-14 days beginning the day after chemotherapy. Prechemotherapy priming with these same doses for four additional days (days -6 to -3) may additionally ameliorate postchemotherapy leukopenia and thrombocytopenia, but with increased risk of toxicity. PMID- 1423183 TI - A phase II evaluation of ifosfamide and mesna in unresectable diffuse malignant mesothelioma. A Southwest Oncology Group study. AB - BACKGROUND: Malignant mesothelioma is a highly treatment-resistant neoplasm. This study represents an attempt to define an effective form of systemic therapy. METHODS: Twenty-six patients with unresectable diffuse malignant mesothelioma were enrolled in Southwest Oncology Group (SWOG) study 8731 and treated with ifosfamide, 2 g/m2 intravenously for 4 days, and mesna 2 g/m2 intravenously for 5 days, every 3 weeks. Patients were either previously untreated with chemotherapy or had at most one prior systemic treatment. RESULTS: Two patients, or 8% (95% confidence interval, 1-25%), achieved partial response, with response durations of 4 and 6 months. One additional patient met criteria for tumor size reduction but not duration criteria. Thirteen (50%) patients had stable disease of 4 months' median duration (range, 1-13 months). The median survival of the entire group was 6.5 months. The dose-limiting toxicity was granulocytopenia (11 patients, < or = 250/microliters). CONCLUSIONS: Ifosfamide/mesna has modest activity in malignant mesothelioma. It could be tested using alternate dosage schedules and in combination with other agents in treating this highly resistant neoplasm. PMID- 1423184 TI - The prevalence of oral lesions in smokeless tobacco users and an evaluation of risk factors. AB - BACKGROUND: The widespread use of smokeless tobacco (ST) has prompted concern in regard to the development of oral lesions in long-term users. METHODS: For inclusion in the current study, a subject must have used an ST product, either snuff or chewing tobacco, for at least 6 months. The subjects were recruited by advertising, and none was referred for the evaluation of an oral lesion. The following were performed on all subjects: assessment of exposure to ST, cigarettes, and alcohol; examination of the oral cavity; a biopsy, if an oral lesion was found; and analysis of a blood sample for beta-carotene. The dietary intake of most of the subjects was analyzed. RESULTS: Of the 347 ST users, all of whom were white male subjects, 45 (13.0%) had an oral lesion. Thirty-five of the lesions were hyperkeratosis and 10 were epithelial dysplasia. CONCLUSIONS: Snuff exposure was associated significantly with the presence of an oral lesion (P < 0.0001). A decreased vitamin C intake also was found among the ST users with oral lesions (P < 0.01). The ST users with epithelial dysplasia, as compared with those with hyperkeratotic lesions, were slightly older, had a lower intake of vitamin C (P < 0.05), and were more likely to have used chewing tobacco than snuff. PMID- 1423185 TI - A flow cytometric analysis of DNA content in primary and metastatic lesions of esophageal squamous cell carcinoma. AB - BACKGROUND: DNA content of malignant tumors has been considered a significant prognostic factor, but intratumor variations in DNA content and differences in DNA content between primary and metastatic lesions have been found in various tumors. METHODS: DNA indexes of multiple samples obtained from different sites in each tumor were determined by flow cytometry (FCM) in 27 esophageal squamous cell carcinomas. RESULTS: Intratumor variation in DNA indexes in primary lesions was found in 10 (37%) of the 27 specimens. Of the rest, all DNA indexes were diploid in 5 and all identically aneuploid in 12 samples. A DNA index differing from that of the metastatic lesion was found in four (50%) of eight primary lesions; however, a component of the DNA index identical to that of metastatic lesion was found in seven (88%) of eight primary lesions. CONCLUSIONS: Recurrence after a "curative" operation was frequent in patients with a tumor that had an aneuploid DNA index, with or without a variation in DNA indexes. There was no recurrence in the five patients with tumors that had only a diploid DNA index. These results suggest that differences in DNA content between primary and metastatic lesions reflect intratumor variation in DNA content in the primary lesions. The presence of a tumor cell population with an aneuploid DNA content, even when the DNA content varied in the primary lesion, may indicate an aggressive clinical course in patients with esophageal squamous cell carcinoma. PMID- 1423186 TI - Malignant lymphoma of the stomach associated with systemic sarcoidosis. AB - The case of a patient with gastric malignant lymphoma associated with systemic sarcoidosis is reported. The patient's sarcoidosis was identified by the findings of bilateral hilar lymphadenopathy and secondary glaucoma. Biopsy of a cervical lymph node showed epithelioid cell granuloma; the sarcoidosis was diagnosed 15 years previously. She had been treated with prednisolone for 5 years until 1979. Proximal gastrectomy, splenectomy, and lymph node dissection were done in 1989. The tumor was diagnosed as malignant lymphoma of the diffuse large cell type according to the Working Formulation. There was no infiltration of lymphoma cell in the 45 dissected lymph nodes, but sarcoid nodules were observed in all nodes. Only three cases of gastric malignant lymphoma complicating sarcoidosis have been reported to the authors' knowledge. Further study should be done in support of the concept of a sarcoidosis-lymphoma syndrome. PMID- 1423187 TI - Declining mortality rates for cancer of the rectum in the United States: 1940 1985. AB - BACKGROUND AND METHODS: Age-standardized and age-specific mortality rates for cancer of the rectum and cancer of the colon were calculated according to race and gender for 1940-1985; age-standardized rates were calculated according to geographic region for 1950-1980. RESULTS: Mortality rates for cancer of the rectum decreased among white and black people of each gender, in most age categories and all regions of the country. Concurrent with this decline, mortality rates for cancer of the colon increased among all race-gender groups except white females, among whom it decreased. CONCLUSIONS: The decline in mortality rates for cancer of the rectum has been largely unappreciated. When deaths occurring from 1940 to 1985 from cancer of the rectum are combined with those from cancer of the colon, mortality rates are increased. However, this combination of sites obscures the divergent trends, which suggest that these cancers have causes that are at least somewhat different. PMID- 1423188 TI - Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis. AB - BACKGROUND: The antibody Ki-67 binds to nuclei in all cell cycle phases except GO and can be used to measure growth fraction. Because proliferative activity has been linked to prognosis in neoplasia, the authors analyzed 100 cases of colorectal carcinoma, each with 3 or more years of follow-up, using Ki-67 immunostaining. METHODS: The Ki-67-positive nuclear area and total nuclear area of carcinoma cells in 20 microscopic fields were measured by computed morphometry. A Ki-67 score (percent positive nuclear area x 100) was calculated. The following characteristics also were recorded for each case: patient age and sex, tumor site and size, modified Dukes' stage, spread beyond bowel wall, lymph node status, tumor grade, histologic type, extramural venous spread, tumor growth pattern, fibrosis, lymphocytic infiltration, and mitotic rate. RESULTS: Ki-67 scores ranged from 1 to 90 (mean, 34.6). Ki-67 scores were higher in Stage A disease (versus Stage B, C, and D disease) but were not associated with survival. Survival curves differed by stage, lymph node metastases, infiltrative growth pattern, lymphocytic infiltration, fibrosis, extramural venous spread, and tumor grade in a univariate analysis. The infiltrative growth pattern (P = 0.04) and lymphocytic infiltration (P = 0.003) were features associated independently with survival after adjusting for modified Dukes' stage. Furthermore, the lack of a significant lymphocytic infiltrate was associated with a death rate 3.4 times greater than that occurring in patients with Stage B disease with a significant infiltrate. CONCLUSIONS: The authors conclude that proliferative activity in colorectal carcinoma as measured by Ki-67 immunostaining was not associated with prognosis. PMID- 1423189 TI - Cytologic examination of pure pancreatic juice in the diagnosis of pancreatic carcinoma. The endoscopic retrograde intraductal catheter aspiration cytologic technique. AB - BACKGROUND: Although cytologic examination of pure pancreatic juice obtained with a duodenofiberscope has been useful for the diagnosis of pancreatic carcinoma, the rate of false-negative results is reported to be high. To eliminate these false-negative results, the authors developed a new technique, endoscopic retrograde intraductal catheter aspiration cytology, especially for an accurate cytologic diagnosis of carcinoma of the body or tail of the pancreas. METHODS: The accuracy of conventional cytologic examination of pure pancreatic juice was assessed in 25 patients with pancreatic carcinoma, 29 patients with pancreatitis, and 52 control subjects. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation using a videoimaging duodenoscope after intravenous administration of secretin. The new endoscopic retrograde intraductal catheter aspiration technique was used in four patients with carcinoma of the body or tail of the pancreas and five patients with localized pancreatitis in whom a correct diagnosis was not made by previous cytologic examination of pure pancreatic juice. RESULTS: Positive cytologic findings were obtained in 76% of the patients with pancreatic carcinoma. Positive cytologic results were more frequent in patients with carcinoma of the head of the pancreas than in those with carcinoma of the body or tail. By the new technique, positive cytologic results were obtained in all of the patients with pancreatic carcinoma. This technique caused no severe complications. CONCLUSIONS: This procedure of endoscopic retrograde intraductal catheter aspiration cytology seems useful for diagnosis of pancreatic carcinoma. PMID- 1423191 TI - Interpleural analgesia through a DuPen catheter for lung cancer pain. AB - BACKGROUND: Pain, one of the most frequent symptoms of lung cancer, is difficult to control at times, not only because of the many structures involved but also because of the paths through which the pain is conveyed. METHODS: When usual analgesic treatment did not alleviate pain after chemotherapy in a patient with lung adenocarcinoma, long-term interpleural analgesia was begun. A DuPen epidural catheter was inserted between the pleura parietalis and visceralis for the administration of bupivacaine in a bolus regimen every 6 hours. RESULTS: Thoracic pain thus was controlled until the patient died 130 days after placement. CONCLUSIONS: The long-term tunneled interpleural placement of DuPen catheters constitutes an alternative to systemic and spinal treatments for thoracic pain due to cancer. PMID- 1423190 TI - Potential impact on tumor control and organ preservation with cisplatin and 5 fluorouracil for patients with advanced tumors of the paranasal sinuses and nasal fossa. A prospective pilot study. AB - METHODS: Twelve patients with advanced epithelial nonadenocarcinoma of the paranasal sinuses and nasal fossa were treated with three cycles of cisplatin (100 mg/m2, day 1) and 5-fluorouracil (1000 mg/m2/24 hours on days 1-5 by continuous infusion), followed by preoperative external radiation therapy of 48 Gy and limited surgery, clearing the paranasal sinuses and nasal fossa. RESULTS: After chemotherapy, 11 of 12 patients were free of the previous symptoms of disease. Clinical response rates were different, however, with an overall response rate of approximately 70% with no complete responses. Histopathologic analysis of resected specimens showed no vital tumor in eight patients, minimal microscopic disease in three patients, and infiltrating tumor in one patient. Local control was achieved in 11 of 12 patients. Ten patients are alive with no evidence of disease (mean follow-up, 27 months). Surgical mutilation was avoided, with no functional or cosmetic loss. CONCLUSIONS: The results of this small pilot study seem to indicate a high chemosensitivity of carcinomas of the paranasal sinuses and nasal fossa, which, in this study, has meant significant relief of symptoms and an unusually high rate of local control (90%) without mutilation. PMID- 1423192 TI - Coagulation-fibrinolysis system and markers of collagen metabolism in lung cancer. AB - BACKGROUND: Evidence suggests that the fibrinolysis system and peritumoral connective tissue play important roles in tumor spread. METHODS: In this study, the authors evaluated the following parameters in 30 consecutive patients with lung cancer: thrombin-antithrombin complex (TAT), cross-linked fibrin split products D-dimer (DD), plasmin-alpha 2-antiplasmin inhibitor complex (PAP), and two antigens related to connective tissue, the aminoterminal propeptide of type III procollagen (PIIIP) and the 7S domain of type IV collagen (7S-collagen). RESULTS: Each parameter was increased significantly in the patients with cancer compared with the control subjects. Except for PIIIP, their concentration in blood was elevated to a significantly greater extent in the patients with distant metastases. The PAP concentration correlated well with the plasma concentration of TAT (r = 0.5; P < 0.01) and DD (r = 0.9; P < 0.0001). There was also a strong correlation between the serum concentrations of PIIIP and 7S-collagen (r = 0.7; P < 0.001). In patients with localized disease, DD levels were correlated significantly with those of PIIIP (Spearman rank-order correlation [rs] = 0.6; P < 0.025) and 7S-collagen (rs = 0.6; P < 0.01). In the group with disseminated metastases, there was a significant inverse relationship between serum PAP concentrations and serum concentrations of 7S-collagen (rs = -0.6; P < 0.025). CONCLUSIONS: These results confirm the presence of a subclinical chronic activation of the parameters of intravascular clotting-fibrinolysis and alterations in the extracellular matrix of patients with lung cancer. These parameters may be useful as indicators of the clinical progression of malignant disease, particularly of lung cancer. PMID- 1423193 TI - Outcome of clinical congestive heart failure induced by anthracycline chemotherapy. AB - BACKGROUND: Anthracycline-induced congestive heart failure (A-CHF) is associated with a high reported incidence of morbidity and mortality. The long-term clinical outcome of patients with clinical A-CHF is less well defined. METHODS: A retrospective chart review was done of 19 patients with a clinical diagnosis of A CHF. RESULTS: In 19 patients, the mean anthracycline dose was 379 +/- 141 mg/m2 (range, 120-570 mg/m2). The median time from the last dose of the drug to the onset of A-CHF was 4 weeks (range, 1-17 weeks). Seven patients (Group I) died of A-CHF within a median of 6 weeks (range, 1-15 weeks) from onset of disease to death. Twelve patients (Group II) had clinical recovery, three with a complete response, eight had partial improvement, and one had stable disease. Most importantly, four patients who had an intercurrent illness (two patients with infections and two with progression of their malignant lesions) had a relapse of clinical congestive heart failure that was fatal. CONCLUSIONS: Many (63%) patients recover from clinical A-CHF. However, the cardiac reserve of these patients is limited, and they may require careful medical management during other illnesses or surgical procedures. PMID- 1423194 TI - "Solid" variant of aneurysmal bone cyst (extragnathic giant cell reparative granuloma) in the axial skeleton and long bones. A study of its morphologic spectrum and distinction from allied giant cell lesions. AB - BACKGROUND: Giant cell reparative granuloma is generally considered to be a benign tumor-like bone lesion. Its involvement of axial skeleton and long bones is rare. METHODS: Seven cases of extragnathic giant cell reparative granuloma (GCRG), which arose in the axial skeleton and long bones, were analyzed clinicopathologically and compared with allied lesions consisting of 31 cases of aneurysmal bone cyst (ABC) and 83 cases of giant cell tumor of bone (GCT). RESULTS: These occurred in patients ranging in age from 8-36 years; two were in the vertebrae; two, in the clavicles; one, in a rib; one, in the humerus; and one in the tibia. None of the patients with GCRG had a recurrence despite incomplete resection. Its skeletal distribution and average associated patient age were similar to those of ABC. Histologically, they were characterized by florid fibroblastic proliferation with osteoclast-like giant cell-rich areas, stromal hemorrhage, and newly formed bone or osteoid trabeculae. The histologic features could be found around either the characteristic aneurysmal cysts or sinuses, although they were lacking any large blood-filled spaces. CONCLUSIONS: The overlapping clinical and histologic features between GCRG and ABC and their similar biologic behavior represent related responses to an intraosseous hemorrhage. The authors prefer to use the term "solid variant of aneurysmal bone cyst" to describe this lesion. PMID- 1423195 TI - Diagnosis and management of giant intrasacral schwannoma. AB - Giant intrasacral schwannoma is a rare cause of a retrorectal mass in an adult patient. Only 21 such tumors have been reported. The diagnosis of this intraosseous nerve sheath tumor is heralded by its minimal symptoms in relation to its often striking radiographic findings and is verified by its unique morphology. Surgical resection is complex because of its anatomic location and propensity for local recurrence. The need for adequate tumor removal must be balanced against the preservation of nerve function. The presentation, diagnosis, and management of intrasacral schwannomas are reviewed, as exemplified in this case presentation and literature review. PMID- 1423196 TI - Emphysematous cystitis due to Clostridium perfringens and Candida albicans in two patients with hematologic malignant conditions. AB - BACKGROUND: Fever, abdominal pain, and hematuria developed in two patients with hematologic malignant conditions (multiple myeloma and agnogenic myeloid metaplasia). Each patient was found to have emphysematous cystitis (EC), secondary to Clostridium perfringens and Candida albicans, respectively. Both patients had debilitated general medical conditions, compromised immune function, prior treatment with broad-spectrum antibiotics and corticosteroids, bladder outlet obstruction, and indwelling Foley catheters as predisposing factors to EC. Neither was diabetic. METHODS: These cases provide an opportunity to review the related medical literature on the pathophysiology and management of this uncommon entity. RESULTS: Treatment consists of control of underlying diabetes (if present), administration of appropriate antibiotics, establishment of urinary drainage, provision of supportive general medical care, exclusion of the presence of a bladder fistula, and surgical debridement only when unavoidable. CONCLUSIONS: EC should be part of the differential diagnosis in patients with cancer who have fever, abdominal pain, and hematuria. PMID- 1423197 TI - A comparative study of DNA ploidy in 115 fresh-frozen breast carcinomas by image analysis versus flow cytometry. AB - BACKGROUND: Qualitative and quantitative analysis of cellular DNA content may be clinically useful in the prognostic evaluation of certain types of malignant tumors, including breast carcinoma. Flow cytometric (FCM) analysis has been the most frequently used procedure for DNA analysis, but it requires a reasonably large tissue sample. Computer-based image analysis (IA) now allows imprint, cytospin, and needle aspiration smear preparations and other small tissue samples to be used. METHODS: To resolve concern about the diagnostic efficacy of small tissue samples in the use of IA, the authors performed a comparative study of FCM analysis and IA using 115 fresh-frozen breast carcinomas. Feulgen-stained imprint preparations for IA and single-cell suspensions from the same fresh-frozen tissue for FCM analysis were used, and the respective histograms were compared. RESULTS: The results were concordant in 90.4% (104 of 115) of the cases, but 11 specimens yielded discordant data. IA provided histograms with a somewhat lower resolution and a relatively high coefficient of variation for the G0/G1 peak, thus rendering occasional tumors, which were near-diploid aneuploid by FCM analysis (four cases), not amenable to diagnosis by aneuploid characterization. In three additional cases, FCM analysis showed aneuploid hyperdiploid (two cases) and multiploid (one case) histograms, but IA only demonstrated a diploid peak. Conversely, in four other cases, aneuploid peaks were recognized only by IA. CONCLUSIONS: Computerized IA has significant advantages over FCM analysis, including lower cost, the ability to analyze very small specimens, the capability of detecting rare high ploidy cells, the capacity to classify cellular populations according to specific morphologic type, and the fact that no destructive enzyme or chemical digestion is required for specimen preparation, thereby preserving the integrity of fragile cells. PMID- 1423198 TI - Immunolocalization of basic fibroblast growth factor to the microvasculature of human brain tumors. AB - BACKGROUND: Microvascular proliferation, a prominent feature of tumors of the central nervous system, is a prime target for anti-cancer therapy. METHODS: Because basic fibroblast growth factor (bFGF) plays a key role in the regulation of angiogenesis, surgical specimens from 52 human brain tumors were examined by immunocytochemical studies with a murine monoclonal antibody to bFGF. Sections from these tumors also were incubated with Ki-67 monoclonal antibody to measure the growth fraction. RESULTS: Immunostaining for bFGF was observed in 45 of 52 (87%) neoplasms, reacting with 97% of the malignant brain tumors and 67% of benign tumors (P < 0.01). The nonreactive tumors were a medulloblastoma and 7 of 21 (33%) benign, noninvasive, slow-growing neoplasms (1 acoustic schwannoma, 3 meningiomas, 2 pituitary adenomas, and 1 cholesteatoma). The indices of proliferation (Ki-67 labeling) were lower for the 21 benign tumors (1.2 +/- 1.1%) than the 31 malignant tumors (10.3 +/- 10.5%; P < 0.001). The bFGF was immunolocalized in the tumor cell nuclei in 23 of 52 tumors (44%) and in the cytoplasm of 8 of 52 (15%) tumors. Immunostaining to bFGF was prominent in the microvascular endothelial compartment in 84% of the malignant tumors and only 52% of benign tumors (P < 0.01). Immunostaining was not present after preabsorption of the antibody with pure human recombinant bFGF. CONCLUSIONS: The presence of bFGF predominantly within the tumor microvasculature indicates a cellular depot for this potent growth factor that mediates angiogenesis and tumorigenesis. These data support a role for bFGF in the transition from the benign to the malignant phenotype. PMID- 1423199 TI - Heterotopic adrenocortical oncocytoma. A case report with light and electron microscopic studies. AB - BACKGROUND: The case of a benign oncocytoma arising in a patient from retroperitoneal heterotopic adrenocortical tissue is reported; this tumor was found in a 44-year-old man. METHODS: The tumor consisted of polygonal cells with granular eosinophilic cytoplasm packed with swollen mitochondria. RESULTS: Scattered tumor cells showed abundant smooth endoplasmic reticulum suggesting that the tumor was of adrenocortical origin. PMID- 1423200 TI - Concurrent radiation therapy, 5-fluorouracil, and cisplatin for stage II, III, and IV, node-negative, squamous cell head and neck cancer. Results and surgical implications. AB - METHODS: Between 1983 and 1989, 42 patients with Stage II, III, and IV, node negative, squamous cell head and neck cancer were treated with concurrent 5 fluorouracil, cisplatin, and radiation therapy. Two courses of chemotherapy with 30 Gy of concurrent radiation therapy were to be followed in all patients by definitive surgery and then an additional 30 Gy of radiation therapy and one to two courses of chemotherapy. The patients who achieved a complete response to the initial induction treatment, however, did not undergo surgery. RESULTS: After the completion of all therapy, 41 of the 42 patients (98%) were considered disease free. Only 4 of these 41 had relapses, for a projected Kaplan-Meier disease-free survival rate of 86%. Treatment failure occurred in no patients with Stage II, 1 of 17 patients with Stage III, and 4 of 14 patients with Stage IV disease. Of the 42 patients, 23 (55%) did not require surgery after achieving a complete response to induction therapy, and only 1 of these 23 patients subsequently had a relapse. CONCLUSIONS: Although the value of adding chemotherapy to conventional treatment remains unproven in squamous cell head and neck cancer, this treatment schedule appears promising in node-negative disease. Randomized trials will be necessary, however, to validate the efficacy of this approach and confirm the suggestion by the authors that surgery can be avoided in most patients with N0 disease. PMID- 1423201 TI - Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for Ewing and soft tissue sarcomas. AB - BACKGROUND: Treatment of cancer with multiple-drug chemotherapy regimens or radiation therapy can cause either temporary azoospermia of various durations or permanent azoospermia in young men. METHODS: To identify which drugs in which doses contribute to long-term or permanent azoospermia, semen analyses were done on patients with Ewing and soft tissue sarcomas before, during, and after treatment with either CYADIC (cyclophosphamide, doxorubicin, and dacarbazine), or CYVADIC (vincristine added to CYADIC). Some patients also received other drugs or radiation therapy. RESULTS: From pretreatment levels that were similar to those of control subjects, sperm production declined to azoospermia within 4 months of treatment. Sperm production returned in some patients after treatment; 40% of men recovered to normospermic levels by 5 years after treatment. Few patients showed continued recovery of sperm production after that time. The cumulative dose of cyclophosphamide was the most significant determinant of recovery to normospermic levels; approximately 70% of those who had received doses less than 7.5 g/m2 (median, 4.1 g/m2) recovered, but only 10% recovered when doses exceeded 7.5 g/m2. CONCLUSIONS: Thus, a risk of permanent sterility is associated with the use of the CYADIC and CYVADIC regimens in young men, especially when the cumulative dose of cyclophosphamide is greater than 7.5 mg/m2. PMID- 1423202 TI - Psychologic adaptation of survivors of childhood cancer. AB - When adult survivors of childhood cancer were compared with their peers, survivors were found to be at least as well adjusted. Indeed, some evidence was suggestive of survivors having adaptive advantages in everyday life. The survivors reported significantly more positive affect, less negative affect, higher intimacy motivation, more perceived personal control, and greater satisfaction with control in life situations. Despite these apparent strengths associated with surviving childhood cancer, several specific problems were documented. Survivors were more likely than peers to have repeated school grades, to be worried about issues of fertility, and to express dissatisfaction with important relationships. The latter finding was interpreted as reflecting the high expectations of survivors for relationships, based on their difficult yet interpersonally rewarding experiences during times of illness. PMID- 1423203 TI - Improved prognosis of children with osteosarcoma metastatic to the lung(s) at the time of diagnosis. AB - BACKGROUND: A poor outcome is traditionally ascribed to osteosarcoma metastatic to the lungs, but data have been unavailable regarding the outcome of such patients after systematic treatment on clinical trials. METHODS: The clinical course and outcome of 31 patients who had osteosarcoma metastatic to the lungs diagnosed between 1962 and 1990 at St. Jude Children's Research Hospital were reviewed to determine whether the use of increasingly aggressive multimodality therapy has improved their outcome. The patients were grouped by treatment eras, based on major changes in therapy (i.e., single-agent or two-agent era, 1962 1972; standard multiagent era, 1972-1982; and intensive multiagent era, 1982 1990). RESULTS: With increasingly intensive chemotherapy, more aggressive efforts to resect metastatic disease, and earlier detection of pulmonary metastases by computed tomography, the survival of these patients has improved significantly over the 28-year study period. Those treated since 1982 have a 50% estimated probability of survival at 3 years, whereas there were no survivors at 3 years in the two earlier eras. Survival for the former group reached a plateau of 30% at 4 years. CONCLUSIONS: The use of aggressive multimodality therapy, coupled with modern pediatric imaging techniques to detect pulmonary disease, has improved the traditionally dismal outlook in pediatric patients with osteosarcoma and synchronous pulmonary metastases. PMID- 1423204 TI - White matter changes in children treated for acute lymphoblastic leukemia. AB - BACKGROUND AND METHODS: Twenty-seven children with acute lymphoblastic leukemia (ALL) were studied by magnetic resonance (MR) imaging after central nervous system (CNS) treatment. The children were followed by clinical evaluations and computed tomographic (CT) brain scans. Two CNS treatment techniques were used. Eleven patients received intravenous and intrathecal methotrexate; 16 patients received 18-30 Gy of cranial radiation therapy in addition to systemic chemotherapy. The time interval between the CNS treatment and MR scans varied from 9 months to 4 years 8 months. RESULTS: Four of the 27 children (15%) showed white matter changes on the MR scans attributable to therapy, but only one had hypodensity on CT. Three of the 16 children (19%) receiving radiation therapy in addition to chemotherapy had white matter changes. One of the 11 patients (9%) from the group receiving only chemotherapy did so. The difference between the two treatment groups was not significant. CONCLUSIONS: Radiation therapy or chemotherapy (alone or in combination) may have been responsible for the white matter changes. MR imaging is a sensitive detector of white matter changes in children with ALL, but its value and significance during follow-up should be assessed in well-designed longitudinal research studies. PMID- 1423205 TI - Does cancer survival differ for older patients? AB - The relation of age to 5-year relative survival rates was examined for leading sites of cancer resulting in death among 127,554 patients; data from 1978 to 1982 were studied for four areas of the Surveillance, Epidemiology and End Results program of the National Cancer Institute. Overall and stage-stratified relative survival rates declined with advancing patient age for cancer of the lung, prostate, pancreas, bladder, oral cavity, uterus, cervix, ovary, and large bowel (women only). In men, this trend was not explained by age differences in stage of diagnosis, whereas, among women, age was associated with more advanced disease for most sites examined. Although overall survival rates were lower in black patients compared with white patients, the age-survival and age-stage trends were similar in the two racial groups. PMID- 1423206 TI - Does endoscopic follow-up improve the outcome of patients with benign gastric ulcers and gastric cancer? PMID- 1423207 TI - Is long-term survival possible with external beam irradiation for stage D1 adenocarcinoma of the prostate? PMID- 1423208 TI - Ifosfamide extrapyramidal neurotoxicity. PMID- 1423209 TI - RNA-directed actions of 5-fluorouridine in hemin stimulated K-562 erythroleukemia cells. AB - The cytotoxic actions of 5-fluorouridine (FUrd) have been evaluated in K-562 erythroleukemia cells, focussing on RNA-directed actions. FUrd was employed such that little DNA-directed cytotoxicity was seen. Substantial inhibition of cellular proliferation was observed at concentrations of FUrd which did not inhibit significantly the activity of thymidylate synthase and which were reversed by less than 10% by exogenous thymidine. In contrast, the syntheses of both poly A- and poly A+ RNAs were substantially reduced. The effects of FUrd on rRNA included reduction by greater than 90% of mature rRNA following a 2 h exposure to 1 microM FUrd, which persisted for at least 48 h, and the appearance of partially processed nuclear rRNA precursors incapable of being metabolized to mature rRNA. FUrd also decreased the levels of several mRNAs, including those for the proto-oncogenes c-myc and c-abl, and for gamma-globin, by 40 to 70%. In contrast to the effects of FUrd on rRNA, decreases in mRNA levels were reversible, and within 12 h following a 2 h exposure to 1 microM FUrd, mRNA levels for each of these three mRNAs were back to those present in untreated control cells. mRNAs did not respond in a connected fashion to FUrd. Thus, levels of beta-actin mRNA were unchanged and levels of ornithine decarboxylase mRNA were increased by exposure to FUrd. These findings demonstrate that FUrd acted in multifarious ways to alter mRNA synthesis and longevity. Inhibitors of individual RNA polymerases were used to analyze the degree to which the FUrd-induced inhibition of RNA metabolism was linked to cytotoxicity. Both actinomycin D, which specifically interfered with the incorporation of FUrd into rRNA transcripts, and alpha-amanitin, which specifically inhibited incorporation of FUrd into mRNA transcripts, decreased the cytotoxicity of FUrd, suggesting that incorporation of FUrd into both mRNA and rRNA precursors plays a role in the RNA directed cytotoxic actions of FUrd. However, the antagonism provided by actinomycin D was greater than that produced by alpha-amanitin, demonstrating that inhibition of rRNA synthesis is the predominant mechanism of cytotoxicity in K-562 cells exposed to FUrd. PMID- 1423211 TI - Modification of the effects of hyperthermia and neutron radiation on the activity of acid phosphatase in CaNT tumors. AB - Acid phosphatase activity was measured in implanted murine CaNT tumors of varying volumes. There is a clear monotonically increasing relation between acid phosphatase activity and tumor volume. Also the tumors were subjected to either induced artificial hypoxia or hyperthermia (41.0 degrees C) alone, or combined with neutron irradiation (3.8 Gy). Changes in the activity of this enzyme following radiation damage could reflect tissue damage associated with metabolic disturbances. The effect on enzyme activity after sequential hyperthermia and neutron irradiation is not synergistic, as is shown in the quantitative experimental data. This implies that the mechanisms of heat damage differ from that of neutron beam damage, as reflected by acid phosphatase activity. The CaNT tumor was also shown to be thermosensitive after administration of mitoxantrone. Finally, the role of exogenous ATP was shown to provide heat protection by modification of those thermal effects resulting in the activity of acid phosphatase. The augmentation of this hydrolytic enzyme probably represents initial metabolic damage in the tumor after different modalities of radiation alone, or combined with mitoxantrone and exogenous ATP. PMID- 1423210 TI - Protein synthetic activity and adenylate energy charge in Rhein-treated cultured human glioma cells. AB - The effect of Rhein (RH) on the protein synthetic activity and adenylate energy charge in human glioma cells cultured in vitro has been investigated. The results demonstrate that in RH-treated cells, the protein synthesis is strongly decreased, but no modifications in the qualitative pattern occur. The extent of inhibition is a function of the drug concentration as well as of the time of exposure. Such an inhibition must be ascribed mainly to a reduction of adenylate energy charge brought about by RH because of its effect on respiration and glycolysis. The correlation between the adenylate energy charge and cell viability, as well as the possibility of using rhein as a biochemical modulator to reduce or to reverse multidrug resistance, are also discussed. PMID- 1423212 TI - Pattern of sialoglycoproteins obtained by chromatofocusing of chicken liver and hepatoma Mc-29 microsomal preparations labelled in vivo with 3H-leucine and N acetyl-14C-mannosamine. AB - Chromatofocusing has been used for separation of chicken liver and virus-induced hepatoma Mc-29 microsomal glycoproteins double labelled in vivo with 3H-leucine and N-acetyl-14C-mannosamine. The sialoglycoprotein profile was obtained by plotting the pH-values, as well as the values of the calculated specific activity (SA-cpm/mg protein) in each fraction, in the graphs. Different patterns for liver and hepatoma sialoglycoproteins were detected. Unlike liver microsomes in which the highest labelled compounds were registered in the alkaline zone of the pH gradient, special feature for the hepatoma sialoglycoprotein pattern was the presence of highly labelled fraction eluted in the acidic zone of the pH gradient. A term named "sialylation rate" of a separated sialoglycoproteins was involved. It has been found that liver sialoglycoproteins are more or less uniformly sialylated, independently of the pI-values, while those from hepatoma with acidic pI were sialylated at a higher extent in comparison to the fractions with alkaline pI. PMID- 1423213 TI - Levels of cytochrome P-450, steroidogenesis and microsomal and cytosolic epoxide hydrolases in normal human adrenal tissue and corresponding tumors. AB - The levels of microsomal cytochrome P-450, steroidogenesis and microsomal and cytosolic epoxide hydrolase activities in normal human adrenal tissue (obtained from adult kidney transplant donors and autopsy material) and corresponding hyperplasia, adenomas and carcinomas (surgical biopsies) were determined. The increased steroid production demonstrated by most of the pathological tissue samples examined here was associated with either an unchanged or dramatically decreased specific microsomal content of cytochrome P-450. Furthermore, specific microsomal epoxide hydrolase activity was also found to be reduced in adrenocortical carcinomas, while the corresponding cytosolic activity was also decreased in at least two of these carcinomas. It is of interest to note in this connection that the level of microsomal epoxide hydrolase in slightly atropic adrenal cortex surrounding adrenocortical carcinomas was also found to be reduced. This would indicate that despite its appearance, this surrounding tissue is not normal in all respects. Thus, adrenocortical carcinomas fit into the common pattern in that their specific contents of microsomal cytochrome P-450 are dramatically decreased, but the simultaneous decrease in their microsomal epoxide hydrolase activity is more unusual. PMID- 1423214 TI - Dysregulation of strongyloidiasis: a new hypothesis. AB - Few other human parasites are associated with such a diverse spectrum of clinical manifestations as Strongyloides stercoralis, yet the basic biological behavior of this unusually versatile worm, particularly with respect to its ability to cause severe disseminated disease in certain hosts, is poorly understood. The current uncritical acceptance of the theory that cell-mediated immunity controls autoinfection has stifled research in other directions. After reviewing what is and is not known about the parasite's behavior in its host, this article explores some of the mechanisms that could be involved in the regulation of the parasite population. Taking the provocative viewpoint that the parasite, not the host, is mainly responsible for the maintenance of a balanced relationship between the two, I propose a new theory that corticosteroids may act on the intraintestinal larvae as molting hormones and directly promote the development of disseminated disease. PMID- 1423216 TI - Advances in nucleic acid-based detection methods. AB - Laboratory techniques based on nucleic acid methods have increased in popularity over the last decade with clinical microbiologists and other laboratory scientists who are concerned with the diagnosis of infectious agents. This increase in popularity is a result primarily of advances made in nucleic acid amplification and detection techniques. Polymerase chain reaction, the original nucleic acid amplification technique, changed the way many people viewed and used nucleic acid techniques in clinical settings. After the potential of polymerase chain reaction became apparent, other methods of nucleic acid amplification and detection were developed. These alternative nucleic acid amplification methods may become serious contenders for application to routine laboratory analyses. This review presents some background information on nucleic acid analyses that might be used in clinical and anatomical laboratories and describes some recent advances in the amplification and detection of nucleic acids. PMID- 1423215 TI - Amebiasis. AB - Entamoeba histolytica, the causative agent of amebiasis, was first described in 1875. Although a large number of people throughout the world are infected with this organism, only a small percentage will develop clinical symptoms. Morbidity and mortality due to E. histolytica vary from area to area and person to person. Recent findings have suggested that there are pathogenic and nonpathogenic strains of E. histolytica that can be differentiated by isoenzyme (zymodeme) analysis, monoclonal antibodies, and DNA probes. Whether pathogenicity is a genotypic trait or can be changed by environmental influences has not been resolved. Exchange of genetic material between strains of amebae can influence zymodeme patterns. Currently, detection of E. histolytica infections depends on examinations for ova and parasites and on serologic tests; however, the development of monoclonal antibodies and DNA probes specific for pathogenic zymodemes may be beneficial for clinical laboratory testing and therapeutic decisions when approved tests become available. A better understanding of the mechanisms of pathogenicity at the molecular level is evolving and should promote the development of vaccines and better target selection for therapeutic agents. PMID- 1423217 TI - Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. AB - Tetracycline has been a widely used antibiotic because of its low toxicity and broad spectrum of activity. However, its clinical usefulness has been declining because of the appearance of an increasing number of tetracycline-resistant isolates of clinically important bacteria. Two types of resistance mechanisms predominate: tetracycline efflux and ribosomal protection. A third mechanism of resistance, tetracycline modification, has been identified, but its clinical relevance is still unclear. For some tetracycline resistance genes, expression is regulated. In efflux genes found in gram-negative enteric bacteria, regulation is via a repressor that interacts with tetracycline. Gram-positive efflux genes appear to be regulated by an attenuation mechanism. Recently it was reported that at least one of the ribosome protection genes is regulated by attenuation. Tetracycline resistance genes are often found on transmissible elements. Efflux resistance genes are generally found on plasmids, whereas genes involved in ribosome protection have been found on both plasmids and self-transmissible chromosomal elements (conjugative transposons). One class of conjugative transposon, originally found in streptococci, can transfer itself from streptococci to a variety of recipients, including other gram-positive bacteria, gram-negative bacteria, and mycoplasmas. Another class of conjugative transposons has been found in the Bacteroides group. An unusual feature of the Bacteroides elements is that their transfer is enhanced by preexposure to tetracycline. Thus, tetracycline has the double effect of selecting for recipients that acquire a resistance gene and stimulating transfer of the gene. PMID- 1423220 TI - Genetics and cytogenetics of retinoblastoma. AB - Retinoblastoma tumor formation is initiated by loss of function of both alleles at the RB1 locus on chromosome 13. In nonhereditary retinoblastoma (60% of patients), both mutations occur during retinal development. In hereditary retinoblastoma (40% of patients), tumor formation is caused by one germline and one somatic mutation. The RB1 gene encodes a nuclear protein that arrests progression through the G1 phase of the cell cycle. In the absence of intact RB1 protein, unscheduled cell proliferation occurs. Genes on chromosomes 1 and 6, which have not yet been identified, appear to be involved in later stages of tumorigenesis. PMID- 1423221 TI - Trisomy 7 in nonneoplastic focal steatosis of the liver. AB - Cytogenetic analysis of short-term cultures of a nonneoplastic focal steatosis of the liver showed trisomy 7 as the sole chromosomal change. This finding, especially when viewed in light of previous reports describing +7 in nonneoplastic tissues, strongly suggests that trisomy 7 cannot be considered a tumor-specific abnormality when it occurs as the only change. The cell type in which +7 is present is not yet known. PMID- 1423222 TI - Cytogenetic and molecular studies of a familial renal cell carcinoma. AB - In a previously studied family with inherited renal cell carcinoma (RCC), RCC was shown to segregate with a constitutional balanced t(3;8)(p14.2;q24.1). In addition, we recently showed that in a RCC tumor from this family the constitutional translocation became unbalanced, suggesting a genetic mechanism that may be associated with the primary genetic events of tumorigenesis. We now report that the RCC tumor cells from this case showed additional cytogenetic alterations, possibly related to tumor progression, which include an additional tumor-specific translocation involving band 14 of chromosome 13. Because this band contains the retinoblastoma (RB) gene, we examined the tumor for aberrations in the RB gene using DNA sequence polymorphism analysis and pulsed-field gel electrophoresis (PFGE), but did not detect alterations in the RB gene. PMID- 1423223 TI - Cytogenetic and fluorescence in situ hybridization analysis of breast fibroadenomas. AB - We report cytogenetic and fluorescence in situ hybridization (FISH) analysis findings in 7 patients with breast fibroadenomas (FA). Three patients were cytogenetically abnormal. One patient had a translocation t(3;5)(p22;q13), the second had trisomy 8, and the third two clones, 47, XX, +11 and 47,XX, +10. PMID- 1423219 TI - Tests for bactericidal effects of antimicrobial agents: technical performance and clinical relevance. AB - Bactericidal testing has been used for several decades as a guide for antimicrobial therapy of serious infections. Such testing is most frequently performed when bactericidal antimicrobial agent therapy is considered necessary (such as when treating infectious endocarditis or infection in an immunocompromised host). It has also been used to ensure that the infecting organism is killed by (not tolerant to) usually bactericidal compounds. However, few data are available to support the role of such tests in direct patient care. Several important variables affect the reproducibility of the test results; however, proposed reference methods are now available for performing the MBC test. With minor modifications, these can provide a standardized approach for laboratories that need to perform them. Currently, little evidence is available to support the routine use of such testing for the care of individual patients. However, testing of new (investigational) antimicrobial agents can be beneficial in determining their potential to provide bactericidal antimicrobial activity during clinical use. New methods to assess bactericidal activity are being developed, but as yet none have been rigorously tested in patient care settings; further, for most of these methods, little information is available as to which technical parameters affect their results. In clinical laboratories, all bactericidal tests must be performed with rigorously standardized techniques and adequate controls, bearing in mind the limitations of the currently available test procedures. PMID- 1423224 TI - t(9;11)(p22;q23) translocation in blastic phase of chronic myeloid leukemia. AB - A patient with chronic myeloid leukemia showed clonal karyotypic evolution, with the appearance of an i(17q) and t(9;11)(p22;q23). This case sheds light upon leukemogenic events related to t(9;11)(p22;q23). The presence of t(9;22) and t(9;11) in the same clone showed that t(9;11) may affect a pluripotent stem cell, thus accounting for t(9;11) in both lymphoid and monocytic leukemias. In this patient, t(9;11) could not be related to a prior cytotoxic exposure and was instead the result of natural evolution of chronic myeloid leukemia. Furthermore, this led us to assume that the phenotype of blast cells may be determined by a chromosome abnormality. A phenotypic conversion from myeloblastic to undifferentiated morphologic aspect was observed when t(9;11) was detected, suggesting that t(9;11) may have induced a loss in differentiation of blast cells affected by this change. This assumption is in agreement with the putative presence of genes activated in pluripotent progenitors by 11q23 rearrangements. PMID- 1423225 TI - Endometrial stromal sarcoma t(7;17)(p15-21;q12-21) is a nonrandom chromosome change. PMID- 1423226 TI - Cytogenetic findings in a breast stromal sarcoma. Application of fluorescence in situ hybridization to characterize the breakpoint regions in an 11;19 translocation. AB - Cytogenetic analysis of a stromal breast sarcoma revealed a complex karyotype that included a reciprocal 11;19 translocation, along with multiple numerical changes, deletions, and other unbalanced structural rearrangements. Karyotypic abnormalities have not been reported previously in this rare neoplasm that arises from mesenchymal breast tissue, and the t(11;19) is of interest because various types of sarcoma are characterized by specific reciprocal translocations. Because of the pericentric nature of the breakpoints on chromosomes 11 and 19 in the t(11;19), classical cytogenetic banding could not reveal the centromeric origin of the translocation derivatives. Using nonisotopic in situ hybridization with chromosome 11 and 19 alpha-satellite probes, the centromere of each derivative chromosome was determined, and the rearrangement was interpreted as a balanced translocation, t(11;19)(q12 or q13.1;p12 or p13.1). This abnormality has not been described previously in any breast tumor. PMID- 1423227 TI - Complex translocation involving Ph chromosome in a patient with typical chronic myelogenous leukemia. AB - We report a cytogenetic study of a patient with chronic myelogenous leukemia (CML) who, while displaying a Philadelphia (Ph) chromosome, resulting from a standard t(9;22) at diagnosis, during the chronic phase (CP) showed disappearance of the Ph and occurrence of new chromosome changes, including a marker probably arising from a translocation involving chromosome 17 and the Ph. In situ hybridization confirmed the cytogenetic appearance and demonstrated that the breakpoint on the Ph marker occurred below the BCR-ABL fusion gene. PMID- 1423218 TI - Chagas' disease. AB - Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS. PMID- 1423228 TI - Cytogenetic features of neonatal leukemias. AB - We reviewed a series of 41 neonatal leukemias (NL), including published cases karyotyped by banding techniques, but excluding Down syndrome-associated cases and analyzed distribution of cytogenetic anomalies with respect to other clinical variables and outcome. The most frequent chromosomal changes in this age group involve rearrangements of 11q23, which is correlated with high white blood cell (WBC) count at onset and type of leukemia. A discrete heterogeneity of cytogenetic abnormalities is also evident, however, possibly reflecting other specific pathways in NL development. With respect to prognosis, cytogenetic abnormalities are a strong indicator of poor prognosis. PMID- 1423229 TI - Application of fluorescence in situ hybridization in hematological disorders. AB - In the present study, chromosome changes in bone marrow (BM) or peripheral blood (PB) cells from 13 patients with malignant hematologic disorders were analyzed by classical cytogenetic techniques (G-banding) and fluorescence in situ hybridization (FISH) procedures using centromere specific probes for chromosomes 1, 6, 7, 8, 9, 12, 18, 13/21, and X, and a DNA probe specific for the long arm of chromosome Y. The cytogenetic data obtained with G-banding were in accord with those obtained by FISH to metaphase chromosomes. Most significantly, FISH to interphase nuclei offered reliable results and in some cases provided important information concerning crucial chromosome anomalies which were not or could not be completely detected by analyzing metaphase chromosomes. Our results indicate that FISH could be clinically valuable in five major areas: 1) marker chromosome identification; 2) identification of trisomy consistent with certain specific hematological neoplasms; 3) clonal evaluation post observation of a single cell with trisomy; 4) clonal evaluation post-sex-mismatched bone marrow transplantation (BMT); and 5) residual disease detection following clinical remission. PMID- 1423230 TI - Pentasomy 21 in leukemia complicating Diamond-Blackfan anemia. AB - We present the cytogenetic pattern of a leukemic infant with Diamond-Blackfan anemia (DBA). The karyotype was characterized by clonal evolution involving consecutive gains of chromosome 21 up to pentasomy. No chromosomal changes were present in normal lymphocytes. Such a karyotype evolution has been described in some cases of acute leukemia associated with Down Syndrome, but rarely in non Down cases. PMID- 1423231 TI - Cytogenetics of a case of cardiac myxoma. AB - The cytogenetic study of a case of cardiac myxoma revealed a 46,XY,der(7)t(7;17) (p21;p11),+der(10)t(10;?)(q22;?),+der(12)t(12;?)(p12;?),del(17)(p11) chromosomal pattern. This case adds a new example of chromosomal abnormalities in benign neoplasms. PMID- 1423232 TI - t(6;9)(p22;q34) associated with acute myeloblastic leukemia (M1) PMID- 1423233 TI - Meningeal hemangiopericytoma or hemangiopericytic meningioma? A cytogenetic and molecular analysis. PMID- 1423234 TI - Translocation (X;1)(p11.2;q21). A subtype of renal adenocarcinomas. PMID- 1423235 TI - Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells. AB - In the t(8;21)(q22;q22) of acute myelogenous leukemia (AML), the breakpoint on chromosome 21 disrupts the AML1 gene, generally in the intron between exons 5 and 6. To isolate fusion transcripts of AML1, and an as yet unidentified gene on chromosome 8 involved in the rearrangement, we used rapid amplification of cDNA ends (RACE) and primers for AML1 exons 5 and 6. A fusion transcript was identified by 3' RACE in the RNA of t(8;21) leukemic cells that also express multiple normal AML1 transcripts. This result clearly indicates that at least one transcriptionally active chimeric gene is generated by the chromosome translocation. This gene on the 8q- derivative represents the fusion between the 5' portion of the AML1 gene with the 3' portion of a chromosome 8 gene that contains a region of sequence homology with the cyclin D2 gene, here referred to as the CDR gene (cyclin D-related gene). The chimeric gene is probably responsible for the pathogenesis of the 8;21 AML. This finding makes it possible to detect the translocation at the molecular level, thus improving the diagnosis and monitoring of the disease in leukemic patients. PMID- 1423236 TI - del(5q) in acute lymphoblastic leukemia with biphenotypic and early progenitor phenotype. AB - We report three patients with acute lymphoblastic leukemia with biphenotypic and early progenitor phenotype who had del(5q). In the first patient, the del(5q) was the sole abnormality; in the second patient, the del(5q) was interpreted as subclonal evolutionary event; while in the third patient, the rearrangement was transiently present 7 months following the diagnosis of Ph-positive ALL, while the patient was in clinical remission. Review of the literature indicates that del(5q) is rare in ALL. In contrast to its presence in AML, del(5q) in ALL is not an adverse prognostic indicator, and it appears to be more frequent in children. PMID- 1423237 TI - Pseudodiploid karyotypes in adenosquamous carcinomas of the lung. AB - Pseudodiploid karyotypes with clonal structural rearrangements were observed in short-term cultures from two adenosquamous carcinomas (ASC) of the lung, a tumor type hitherto virtually uncharacterized cytogenetically. The karyotypes were 46,XX,der(1)t(1;14)(q44;q22),add(9)(q34) in the first tumor and 46,XX,i(17)(q10) in the second tumor. We suggest that ASC of the lung differ from other lung cancers by having pseudodiploid instead of massively aneuploid tumor stemlines. PMID- 1423238 TI - Abnormalities of chromosome 18 in myelodysplastic syndromes and secondary leukemia. AB - Monosomy 18 and partial deletion of 18q are nonrandom events in myelodysplastic syndromes (MDS) and secondary acute myeloblastic leukemia (sAML). They are part of complex chromosome abnormalities, as shown in the present study of six patients with MDS and sAML. We compared occurrence of chromosome 18 abnormalities in these syndromes with that in de novo AML. PMID- 1423239 TI - Partial characterization, progressive development and correlations of some neoplastic characters in 20-methylcholanthrene-induced transformed murine embryonal fibroblasts. AB - Non-trypsinized primary fibroblast cells from 20-day-old Swiss mouse embryo was transformed by 20-methylcholanthrene (MCA) and was designated as CNCI-PM-20. The progressive development of some transformation related characters such as morphological alterations, reduced population doubling time, increased saturation density, reduced serum requirement, increased plating efficiency, loss of density dependent growth inhibition, anchorage-independent growth and tumorigenicity in mice clearly demonstrated the multistep process of carcinogenesis as well as the neoplastic nature of the cell line. Furthermore, the association of reduced requirement of serum and loss of density-dependent growth inhibition with tumorigenicity were also observed. Finally, anchorage-independent growth, greater malignant nature of transformed foci and increased number of giant cells may be required for tumorigenicity of this cell line. PMID- 1423240 TI - Modulation of the anti-proliferative signal of interferon-alpha by tamoxifen in U937 cells. AB - Several clinical protocols are attempting to utilize the combined anti proliferative signal of interferon-alpha (INF-alpha) and tamoxifen on cancer cells. We demonstrated here that the effect of these two agents on the growth of the premacrophage U937 cells is antagonistic. This antagonistic effect is paralleled by the ability of tamoxifen to modulate the INF-alpha-induced hyperpolarization in these cells. INF-alpha-induced hyperpolarization was shown before to be an integral part of the anti-proliferative signal of this agent. Tamoxifen liberates Ca2+ from intracellular stores of U937 cells but this effect of the drug is not the cause of its antagonistic effect with the anti proliferative signal of IFN-alpha. We suggest therefore, that the combined effect of these two anti-cancer drugs could also be advantageous for macrophage proliferation. PMID- 1423241 TI - Carcinogenesis induced by a single administration of 1,2-diethylhydrazine in female rats of various ages. AB - Three- or fourteen-month-old female L10 rats were exposed to a single intravenous injection of 1,2-diethylhydrazine (SDEH) at 150 mg/kg of body weight. At the 95th week after carcinogen treatment when the experiment was stopped, 30.7% and 4.5% of rats from the younger and older groups survived, respectively. Total tumor incidences were 68.8% and 84.6%, respectively, in rats treated with SDEH at the age of 3 or 14 months vs. 18.2% and 34.5% in corresponding young and old controls (P < 0.01). Leukemias, thyroid adenomas, uterine tumors and mammary malignancies developed more frequently in animals exposed to carcinogens than in control groups. No age-related differences in tumor incidence or localization between rats exposed to SDEH at various ages were observed, but tumors developed earlier in older groups than in younger groups. The results supported the suggestion that the accumulation of initiated cells in some tissues during natural aging is a cause of the age-related increase in cancer incidence. PMID- 1423242 TI - Multiple effects of 3-aminobenzamide on DNA damage induced by cisplatin (DDP) in DDP-sensitive and -resistant rat ovarian tumor cell lines. AB - To investigate the mechanisms by which 3-aminobenzamide (3AB) reverses cisplatin (DDP) resistance in a rat ovarian tumor cell line, the effects of 3AB on DDP induced DNA damage and repair were kinetically determined over a post-exposure period of 48 h. DNA single strand breaks (SSB) occurred maximally 12 h and 24 h following DDP exposure in DDP-resistant (O-342/DDP) and -sensitive (O-342) rat ovarian tumor cells, respectively. 3AB, present during and after the exposure, significantly increased SSB formation by DDP at 24 h (P < 0.02) and 48 h (P < 0.01) in O-342/DDP cells. To a lesser extent (P > 0.05), a similar tendency was also observed in O-342 cells. Formation of DNA interstrand cross-links (ISCL) by DDP reached a maximum by 12 h in either O-342 or O-342/DDP cells, but in the resistant cells they were both much lower and more rapidly removed. 3AB decreased ISCL in the sensitive cells at 12 h and thereafter with a maximum at 24 h (P < 0.05), while in the resistant cells the same treatment decreased ISCL at 12 h, had no effect at 24 h and increased ISCL at 48 h following DDP treatment. Therefore, it is concluded that 3AB has multiple effects on DNA damage and repair induced by DDP in both cell lines and increase of DNA-ISCL by 3AB at 48 h after the exposure in O-342/DDP cells might be related to its chemosensitizing effect in this line. PMID- 1423243 TI - Expression of p43 in breast cancer tissue, correlation with prognostic parameters. AB - Placental isoferritin (PLF) and its unique superheavy chain p43 have been recently described as being synthesized by breast cancer cell lines but not by normal breast epithelial cells. Since previous reports have demonstrated a correlation between the content of 'normal' ferritin in breast cancer tissue and the degree of differentiation and prognosis, we have determined p43 in the cytosol of 122 breast cancer samples by use of the new monoclonal antibody CM-H 9. The synthesis of p43 showed a significantly negative correlation with tumor size (P = 0.0001), histologic grading (P = 0.0038), nuclear pleomorphism (P = 0.0019), rate of mitosis (P = 0.0002), lymphocytic reaction (P = 0.0001) and a significantly direct correlation with estrogen receptor status (P = 0.0009). Although patients with a higher p43 content showed a trend for a better outcome (median follow-up: 61.4 months), an independent influence of the cytosolic p43 content on survival could not be confirmed by a multiple Cox model. Therefore it seems that p43's prognostic impact is linked to the highly significant correlation with features of differentiation although a statistical bias in the Cox model due to the limited number of patients must also be taken into account. On the other hand, the significant correlation of p43 expression with factors for good prognosis was striking and consistent and warrants further research of this tumor product. PMID- 1423244 TI - Detection of carcinoembryonic antigen in colonic effluent by specific anti-CEA monoclonal antibodies. AB - To characterize the CEA in colonic effluent, anti-CEA monoclonal antibody COL-4 was used in a qualitative radioimmunoassay in both fractionated and unfractionated colonic effluent. Both effluent samples and tissue extracts, were subjected to Western blotting and tissue sections to immunohistochemistry. Quantitative levels of colonic effluent CEA were determined by a kit (Abbott EIA). Higher mean values of COL-4 binding activity were seen only in patients with a past history of polyps (P < 0.01). Quantitated CEA correlated with the presence of colorectal cancer (CRC) as compared to normal subjects, (1133 +/- 875 vs. 459 ng/ml +/- 602, P < 0.05) but not when standardized for protein content. COL-4 reacted with an 180,000 M(r) CEA in the effluent and activity was associated with membrane fraction of the effluent, but bore no relation to the immunohistological staining. We conclude that CEA is detectable in colonic effluent and is membrane associated, but the overlapping values in effluent samples do not make this a useful test in the diagnosis of CRC. PMID- 1423245 TI - Evidence of hypothalamic involvement in the mechanism of transplacental carcinogenesis by diethylstilbestrol. AB - Disruption of hypothalamic sex differentiation in the fetus is one hypothesis to explain female reproductive system anomalies and cancer arising from prenatal exposure to diethylstilbestrol (DES). To further test this hypothesis, breeding performance and behavior were monitored in a colony of mice exposed prenatally to DES, using a schedule previously shown to produce anomalies and cancer of the female reproductive system. Fertility decreased with age more rapidly in DES exposed females than in control females. DES-exposed females were less accepting of the male than control females. These observations support the hypothesis of abnormal hypothalamic sex differentiation as a basic mechanism in DES transplacental carcinogenesis. PMID- 1423246 TI - Adenoma-derived antibody, Adnab-9 recognizes a membrane-bound glycoprotein in colonic tissue and effluent material from patients with colorectal neoplasia. AB - The binding in pre-colonoscopic effluent of Adnab-9, a monoclonal antibody raised against colonic adenomas, was evaluated for specificity in the diagnosis of colorectal cancer. A heterogeneous group of 58 patients was evaluated by ELISA. Effluent samples and tissue extracts were subjected to Western blotting or ELISA to confirm specificity. Immunohistochemistry was performed on the cancer tissue sections. The proportion of positive effluent binding was higher in the cancer when compared to the normal group (P = 0.036). A dominant 87 M(r) band was found in adenoma extracts and some effluent samples. Adnab-9 binding in effluent samples predominated in membrane-bound fractions. Immunohistochemistry showed no specific staining in the cancer cells. The antigen recognised is a glycoprotein shown by effects of N-glycanase digestion and not cross-reactive with carcinoembryonic antigen. Non-gastro-intestinal tissue extracts did not bind Adnab-9. The major 87 M(r) adenoma-derived antigen may be found in effluent material, particularly in the membrane-bound fraction. PMID- 1423247 TI - C-ets-1 protooncogene expression alters the growth properties of immortalized rat fibroblasts. AB - Ets family genes have been cloned and characterized from a variety of species ranging from human to Drosophila. The ets proteins encode transcription factors that activate transcription via specific binding to GGAA core sequence present in various promoter/enhancers. To investigate the role of ets protooncogene expression on the growth properties of rat embryo fibroblasts (REF), we constructed and introduced ets expression vectors into primary, as well as immortalized REF cells. The transfected cells contained multiple copies of the vector DNA, and the Northern blot analysis demonstrated overexpression of the c ets-1-specific mRNA. Although the expression of the ets genes was unable to immortalize primary rat embryo fibroblasts, the expression of ets-1 in REF-1 cells enabled their growth in serum-free medium and effected tumorigenic activity in nude mice. PMID- 1423248 TI - Immunosurveillance by T-lymphocytes in pretumoral stages of chemically induced pancreatic carcinogenesis. AB - Cellular immune-response during pancreatic carcinogenesis induced by N-nitroso bis(2-hydroxy-propyl)amine in Syrian Golden hamsters was studied using a mouse antiserum to hamster T-lymphocytes in indirect immunofluorescence. The chronology of lesions in this model is, acinar cell atypia, cystadenoma, ductal hyperplasia and adenocarcinoma. Lymphocyte infiltration began before microscopic lesions. Starting as an interstitial and interlobular migration, this earliest population was composed of various kind of mononuclear cells including T-cells. As pancreatic lesions proceeded, an abundant lymphocyte supply through newly formed capillaries (angiogenesis), gave rise to inter- and intralobular nodules composed almost exclusively of T-cells. Migrating from nodules, T-cells invaded and readily destroyed the exocrine tissue. Formation of hyperplasic ducts and of adenocarcinoma was accompanied by considerable accretion of the basal membrane (fibrosis). T-cells were located outside and around this basal membrane so that they never invaded the ductal epithelium. Our results suggest there is an effective immunosurveillance in the early stages of transformation that becomes ineffective at later stages as a consequence of T-cells' inability to pass through the basal membrane barrier surrounding the ductal epithelium in preneoplasic lesions (ductal hyperplasia) and in adenocarcinoma. Extending our observations to human pancreatic cancer could provide a new insight in cellular immunosurveillance and, as a consequence might, help cellular immunotherapeutic approaches for this almost fatal disease. PMID- 1423249 TI - Effects of dietary fat on hepatic microsomal and cytosolic mutagenic activation of 2-aminofluorene. AB - The present study was designed to examine the effects of different high fat diets on the liver microsomal and cytosolic mutagenic activation of 2-aminofluorene. Male Sprague-Dawley rats were fed either a low fat (5% corn oil) or high fat (20%) diets containing either corn oil (CO), menhaden oil (MO) or beef tallow (BT). After 2 weeks on the test diets, animals from each group were placed on a protocol of weekly injection with 1,2-dimethylhydrazine dihydrochloride (DMH) for 10 weeks. Animals were given DMH injections i.p. and killed 3 h after injection following 5 and 10 DMH treatments. The metabolic activity of liver microsomes and cytosol was assessed by the Ames test using 2-aminofluorene as a standard mutagen. Beef tallow-fed rats had the highest microsomal mutagenic activation, followed by the basal diet. Decreased liver microsomal and cytosolic metabolism of the reference mutagen was detected in the MO and CO diets compared to basal or BT diets. However, there was an increased activity in MO and CO fed groups after week 10, while beef tallow showed a slightly decreased activation. These data indicate that type of dietary fat affects liver microsomal mutagenic activation of carcinogens. PMID- 1423250 TI - Nursing care for oral complications associated with chemotherapy. A survey among members of the Dutch Oncology Nursing Society. AB - The incidence of oral complications among adult cancer patients undergoing chemotherapy varies from 12% to 80%. Adequate oral hygiene has been shown to be important in prevention, and an essential role is reserved for the nursing staff. These considerations prompted the decision to survey, by means of a questionnaire, the nurses who give care to cancer patients. The questions were concerned with multidisciplinary treatment, inspection methods, nursing interventions, and nursing education. Data emerged regarding a shortage of dentists and dental hygienists, and knowledge of oral inspection and the appropriate interventions by nurses are insufficient. Extra attention to oral hygiene during training is warranted. PMID- 1423251 TI - Knowledge of colorectal cancer among older persons. AB - Cancer screening is a national health priority, especially for colorectal cancer, the second leading cause of death due to cancer in the United States. The researchers measured colorectal cancer knowledge among 211 older Americans. A quasiexperimental pretest-posttest two-by-two factorial design was used to test the effect of knowledge on participation in fecal occult blood screening. The American Cancer Society's colorectal cancer educational slide-tape presentation served as the basis for all of the educational programs. Hemoccult II kits were distributed at no cost to the participants. Descriptive statistics, chi 2, and logistic regressions were used to analyze data. One-half of the participants had incomes below the poverty level. Almost one-half the subjects in the study sample stated that they had not received any information about colorectal cancer within the past year. Caucasians had more knowledge of colorectal cancer than African Americans [F(1, 78) = 7.92, p < 0.01] and persons with higher income had more knowledge than persons with less income [F(2, 76) = 3.01, p = 0.05]. Subjects showed significant increases in colorectal cancer knowledge 6 days after the colorectal cancer education program [t(79) = 2.59, p = 0.01] and this increased knowledge was a predictor of participation in free fecal occult blood screening [chi 2(1, n = 164) = 5.34, p = 0.02]. PMID- 1423253 TI - Cancer patients' interest in group support programs. AB - Extended periods of remission from cancer have led to an increasing number of patients coping with problems in day-to-day living. Attendance at group support programs that address these problems has been low, however, and only certain subgroups of cancer patients seem to be attracted to them. This study consisted of gathering qualitative and quantitative information from 73 cancer patients concerning factors that might influence participation in group support programs. Only 25% of the patients expressed an interest in group programs. The main reason for interest was the opportunity for mutual support and exchange of experiences. On the other hand, the most common reasons for lack of interest among the 75% who were not interested in group programs were doubts about the usefulness of patient groups and/or the impression that other kinds of support were more important. The ratio 1:3 (one person interested versus three persons not interested) was distributed across most of the analyzed sociodemographic and cancer-related variables. A logistic regression analysis showed that patients indicated significantly more interest in group programs when they had been diagnosed within the previous 14 weeks (p < 0.033). Less-educated individuals were more likely to be interested in groups (p < 0.055). Implications of the study findings are discussed with regard to the future design of support group programs. PMID- 1423252 TI - Pharmacological management of cancer pain. A guide for the health care professional. AB - Cancer pain continues to remain a significant problem for oncology patients treated in both the university and the community setting. Nursing knowledge regarding pain management has advanced significantly in recent years. This article provides health care professionals with current factual information on cancer pain management. The information focuses on the emotional aspects of cancer pain, specific principles of analgesic management, opioid equianalgesics, multiple approaches to opioid administration, management of unwanted side effects, and a description of inappropriate drug therapies. PMID- 1423254 TI - What do cancer patients' spouses know about the patients? AB - A large body of research shows that social support in general and of family members in particular plays an important role in determining cancer patients' quality of life. We assumed that the spouse's information about how the patient experiences the situation determines the spouse's ability to help. The present study was designed to examine how much the spouse knows about the attitudes and experiences of their husband or wife who is a cancer patient, and whether this knowledge depends on the questions' structure, disease duration, its severity, or level of patient's information about the disease and prognosis. A questionnaire with multiple-choice and open-ended questions assessing 13 domains (e.g., fears and worries concerning health, functioning in the family, and anxiety) was administered to patients and their partners. Subjects were 55 head-and-neck cancer patients, 40 men and 15 women, with disease stages I to IV, grade of tumors G1 to G3-4, and disease duration of 0.5 to 21 years. The results showed that correspondence between the patients' and their spouses' responses was very low, and was not affected by the structure of the questions or the disease's duration and severity. Correspondence was high only in patients informed about their disease. In the discussion, it was pointed out that when the patient is informed, communication channels in the family are opened and this brings about an increase in the spouses's information about the patient and hence in the spouse's ability to provide the patient the needed social support as a psychotherapeutic agent and a friend. The cancer nurse may play a crucial role in instituting the patient-spouse dialogue. PMID- 1423255 TI - Uncertainty and anxiety after mastectomy for breast cancer. AB - The purpose of this study was to determine the relationship between uncertainty and anxiety in women after mastectomy for breast cancer and to describe women's responses to partial or complete mastectomy for breast cancer during the early rehabilitative phase after surgery. A theoretical framework for the study was derived from the Scott, Oberst, and Dropkin Stress-Coping Model and from a review of the literature. Major study variables and variable measures were uncertainty, measured by the Mishel Uncertainty in Illness Scale (MUIS), and anxiety, measured by the State-Trait Anxiety Inventory (STAI). Twenty-five women admitted to two acute-care teaching hospitals for their first partial or modified radical mastectomy made up the convenience sample of this study. Data were collected 1-2 days before and 1-2 weeks after hospital discharge. From study findings, it was shown that only at the postdischarge testing was there a significant positive correlation between uncertainty and state anxiety. The development of appropriate interventions to assist breast cancer patients in dealing with the fears of recurrence and uncertainties regarding treatment effectiveness and sequelae has relevance for nursing practice. PMID- 1423256 TI - Constipation related to narcotic therapy. A protocol for nurses and patients. AB - Constipation is a well-known side effect of narcotics and can add to the total burden of pain of cancer patients in need of pain medication. There is little literature on this topic, and it has been suggested that one reason is that the definitions are vague and socially bound. It has also been suggested that some physicians consider constipation a trivial problem, resulting in a relative lack of attention to the subject. Although this article addresses narcotic-induced constipation, other types related to poor dietary and exercise habits and to disease are mentioned and may be contributing factors. There are a number of drugs and treatments available to treat the problem, but the emphasis of nursing care should be on prevention of constipation. Senna derivatives have been noted to reverse the major constipating effect of narcotics, i.e., the decrease in propulsive movements of the colon, and it is recommended they be given right along with narcotics as a preventive measure. A protocol that incorporates a schedule of drugs and dosages and specific patient and nursing guidelines for daily evaluation of bowel function, with education about dietary, fluid, and exercise requirements, will help nurses practice prevention and contribute to patients' comfort. PMID- 1423257 TI - Totally implantable venous access ports--the patients' point of view. A quality control study. AB - After implanting > 150 totally implantable venous catheters, 40 patients were interviewed about their experiences by telephone using a standard questionnaire. There were 25 women and 15 men, all having or having had chemotherapy for nonresectable advanced cancer, 26 of them by means of a portable pump. Almost all patients thought that the advantages of the Port-a-Cath (PAC) outweighed its disadvantages; they were not hindered in their daily activities, and none of the patients experienced problems with sexual intercourse because of the PAC. Drawbacks of the method are that 40% of the patients found the operation for insertion of the PAC to be more painful than they had expected. Although PAC reduced the fear of repeated peripheral vein puncture, puncture of the PAC was viewed as painful by 15 of the 40 patients. We conclude that a PAC seems to be preferable to an external catheter but that pre- and postoperative patient information needs to be improved. PMID- 1423258 TI - Mouse monoclonal antibodies which recognize a human (beta 1-4)galactosyl transferase associated with tumor in body fluids. AB - Mouse monoclonal antibodies against human (beta 1-4)galactosyl-transferase (GalT) purified from human ovarian tumor effusion fluids were prepared and characterized. GalT purified from normal human plasma showed a single diffused band in nondenaturing polyacrylamide gel electrophoresis, but GalT purified from human ovarian tumor effusion fluids showed several oligomeric bands and a monomeric band in nondenaturing polyacrylamide gel electrophoresis. These oligomeric bands were dissociated into monomer by urea treatment and polymerized by a 2-mercaptoethanol treatment. Nine monoclonal antibodies (MAb) were prepared by immunization of purified GalT from human ovarian tumor effusion fluids and classified into three groups. Type I MAbs (MAb8611, MAb8913, and MAb8919) reacted only to the GalT monomer. Type II MAbs (MAb4880, MAb8507, and MAb8628) reacted to both the GalT monomer and the GalT polymer. Type III MAbs (MAb7907, MAb8513, and MAb8677) reacted only to the GalT polymer. These MAbs except MAb7907 could recover GalT enzyme activity from effusion fluids by immunoprecipitation. A fraction passed through MAb8513 affinity chromatography still showed reactivity to MAb8919, demonstrating that an epitope of MAb8513 resides on a minor part of GalT. A sandwich immunoassay (MAb8513-MAb8628HRP) was developed, and serum samples from ovarian cancer patients and benign ovarian patients were tested. The levels of sandwich immunoassay of serum samples from cancer were elevated significantly compared to those from benign and did not necessarily correlate to total GalT enzyme activity in serum samples. These results suggested that MAb8513 (Type III) might recognize a unique GalT associated with tumor (GAT). PMID- 1423259 TI - Responses to retinoic acid of tamoxifen-sensitive and -resistant sublines of human breast cancer cell line MCF-7. AB - Growth of the human breast cancer cell line MCF-7 is known to be inhibited both by antiestrogens such as 4-hydroxytamoxifen (OHTAM) and by retinoic acid (RA). Uncloned MCF-7 cells (UNC) and two cloned sublines, one sensitive to antiestrogens (E-3) and the other resistant to them (RR), were used in this study. Growth of UNC and E-3 was inhibited by either OHTAM (10(-7) M) or RA (10( 6) M), and this inhibition could not be overcome by the simultaneous addition of estradiol. Subline RR, which was originally selected for resistance to tamoxifen, was resistant to both OHTAM and RA as measured by either growth in culture or colony forming ability. RR was resistant to RA at all concentrations tested between 10(-9) M and 10(-6) M. The inhibition of uncloned MCF-7 cells by RA was dose dependent between 10(-9) M and 10(-6) M. Subline E-3, however, exhibited a mixed response to RA. At 10(-9) M and 10(-8) M, growth was stimulated, but at 10( 7) M and 10(-6) M it was inhibited. The level of estrogen receptor was measured in the same experiment by using a whole cell assay. In the uncloned MCF-7 cultures and in both the RR and E-3 sublines the level of estrogen receptor was increased between 50 and 200% by RA. The production of plasminogen activator by MCF-7 cells is stimulated by estrogen. RA had a dual effect on plasminogen activator production. In the absence of estrogen, RA inhibited production below the unstimulated level, but in cells stimulated by estrogen, RA increased plasminogen activator production. The results reported here support possible interactions between the mechanisms by which cells respond to estrogen, antiestrogens, and retinoids. PMID- 1423260 TI - Intrathecal 4-hydroperoxycyclophosphamide: neurotoxicity, cerebrospinal fluid pharmacokinetics, and antitumor activity in a rabbit model of VX2 leptomeningeal carcinomatosis. AB - Dissemination of tumor to the leptomeninges and cerebrospinal fluid represents a common pattern of metastasis for many cancers; however, few chemotherapeutic agents are available for intrathecal (i.t.) use and treatment results are often poor. We studied the neurotoxicity and pharmacokinetics of i.t. 4 hydroperoxycyclophosphamide (4-HC) in the rabbit and the activity of i.t. 4-HC in a VX2 rabbit model of leptomeningeal carcinomatosis to evaluate the potential use of 4-HC in the treatment of leptomeningeal tumors. Toxicity studies examined 4-HC doses ranging from 0.5 to 6.0 mumol administered by intraventricular injection weekly for 4 to 8 weeks. Clinical or histological neurotoxicity was not observed in rabbits treated with < 1.0 mumol 4-HC for 4 weeks. Clinical toxicity, characterized by lethargy, weight loss, seizures, or death, was apparent at doses > 2.0 mumol. Vasculitis of superficial arteries was observed in rabbits treated with > 1.0 mumol 4-HC. In cerebrospinal fluid pharmacokinetic studies, the mean drug half-life after intraventricular or intralumbar administration was 24.3 and 18.2 min. Regional inequities in drug exposure were apparent as area under the clearance curve values for cerebrospinal fluid distant from the injection site were lower than those of proximate sites (P < 0.001). Weekly intraventricular treatment of VX2 leptomeningeal tumor-bearing rabbits with 0.5 or 1.0 mumol of 4 HC resulted in an increased life span of 22.5 and 35%, respectively. These results indicate that i.t. 4-HC, at doses lower than those producing neurotoxicity in the rabbit, is effective treatment for VX2 leptomeningeal carcinomatosis. PMID- 1423261 TI - Comparison of cellular accumulation and cytotoxicity of cisplatin with that of tetraplatin and amminedibutyratodichloro(cyclohexylamine)platinum(IV) (JM221) in human ovarian carcinoma cell lines. AB - We have compared the cellular accumulation and cytotoxicity of three platinum compounds in a panel of five human ovarian carcinoma cell lines. The cell lines, which were established from both untreated and pretreated patients, showed a wide range in sensitivity to cisplatin and other platinum drugs. The panel consisted of two sensitive (41M, CH1), one in vivo acquired resistant (PXN/94) with moderate sensitivity, and two intrinsically resistant (SKOV-3, HX/62) cell lines. The cisplatin 2-h concentration of drug required to inhibit cell growth by 50% compared with vehicle treated control cells (IC50 values) for these cell lines were in the following order: CH1 < 41M < PXN/94 < SKOV-3 < HX/62. None of the cell lines showed saturation of platinum accumulation (per mg protein) at 2 h after exposure to cisplatin concentrations of up to 500 microM. The highest cellular platinum accumulation was observed in the sensitive 41M cell line which was established from an untreated patient. The lowest accumulation was found in the intrinsically resistant HX/62 cell line. The rate of platinum accumulation at an equimolar concentration of cisplatin was 41M > SKOV-3 > CH1 > PXN/94 > HX/62. The relationship between drug accumulation and cytotoxicity was evaluated by comparing 2-h IC50 values with platinum accumulation following exposure to both equimolar and equitoxic doses of the agent. The results suggest that reduced drug accumulation may play a partial role in the mechanism of intrinsic resistance to cisplatin in one cell line (SKOV-3) and a major role in another (HX/62), where reduced accumulation is attributable to reduced uptake rather than enhanced efflux. Decreased drug accumulation may also contribute significantly to the lower sensitivity of the PXN/94 cell line to cisplatin. Interestingly, both the PXN/94 and the sensitive CH1 cell lines, which were established from patients pretreated with platinum drugs, showed reduced drug accumulation relative to the 41M cell line. Cellular accumulation of tetraplatin and JM221 [(ammine)dibutyratodichloro(cyclohexylamine)platinum(IV)], a novel platinum(IV) dicarboxylate complex exhibiting enhanced cytotoxicity compared to cisplatin, was also examined. Comparison with platinum accumulation from cisplatin suggests that the increased cytotoxicity of tetraplatin and JM221 may be related to their increased accumulation. Significantly both agents are more lipophilic than cisplatin, which may account partially for their improved uptake in cisplatin resistant cells. PMID- 1423262 TI - Mutation spectrum of the p53 gene in bone and soft tissue sarcomas. AB - We present here an analysis of the spectrum of mutations of the p53 gene seen in 127 bone and soft tissue sarcomas of various histological classifications. Gross rearrangements were analyzed by Southern blotting using a complementary DNA probe from the p53 gene, and subtle alterations in the entire coding sequence (exons 2 through 11) were identified by a combination of single-strand conformation polymorphism analysis and direct genomic sequencing. A total of 42 somatic alterations of the p53 gene were found, of which 21 were gross rearrangements and 21 were subtle alterations. These included 17 cases of a single base substitution, 3 small deletions, and one single base insertion. In contrast to reported findings for other types of cancer, we found that mutations of the p53 gene in sarcomas are quite heterogeneous both in their distribution throughout the gene and in the type of genetic alterations that result. All 13 missense mutations we found occurred at highly conserved residues, whereas 8 nonsense mutations occurred at sites that spanned the gene from codons 46 to 316. Surprisingly, approximately one-half of the osteosarcomas with allelic deletions on 17p did not have detectable alterations in the coding sequence of the p53 gene. PMID- 1423263 TI - pH in human tumor xenografts and transplanted rat tumors: effect of insulin, inorganic phosphate, and m-iodobenzylguanidine. AB - Various strategies to improve the therapeutic index of anticancer agents aim at inducing, by stimulation of aerobic glycolysis, temporary pH differences between malignant and normal tissues which can be exploited to activate cytotoxic agents selectively in tumors. We have investigated whether the pH reduction induced by glucose, the "drug" commonly used to increase lactic acid production in malignant tissues, can be augmented by pharmacological manipulation of tumor cell glycolysis. At normal plasma glucose concentration (6 +/- 1 mM), inorganic phosphate, a modifier of hexokinase and phosphofructokinase activity, had no effect on pH in two transplanted rat tumors and a human tumor xenograft line (average pH, 6.80; range, 6.65-6.95). When plasma glucose concentration was raised to 30 +/- 3 mM by i.v. infusion of glucose, inorganic phosphate reduced the pH in those tumors which exhibited only a moderate pH response to glucose per se (mean pH, 6.60) to an average value of 6.20 (range, 6.05-6.35). In the same setting, insulin, continuously infused at dose rates up to 600 milliunits/kg body weight/min, did not result in acidification of tumor tissue exceeding that induced by glucose alone. However, the H+ ion activity in both transplanted rat tumors and human tumor xenografts was increased by m-iodobenzylguanidine (MIBG), an inhibitor of mitochondrial respiration. For example, at normoglycemia, MIBG reduced the mean pH in a human mesothelioma xenograft from 6.90 to 6.70. This pH value was further reduced to 6.20 by simultaneous low-dose i.v. glucose infusion (plasma glucose concentration, 14 +/- 3 mM). The acidosis induced by inorganic phosphate and MIBG was tumor specific. Normal tissues of tumor-bearing hosts were only marginally sensitive to hyperphosphatemia or MIBG administration. These results indicate that the known stimulatory effect of exogenous glucose on lactic acid production in malignant tumors in vivo can be further accentuated or, as in the case of MIBG, partially replaced by pharmacological manipulation of aerobic glycolysis using clinically established drugs. PMID- 1423264 TI - Intra- and interindividual variability in systemic exposure in humans to 2-amino 3,8-dimethylimidazo[4,5-f]quinoxaline and 2-amino-1-methyl- 6-phenylimidazo[4,5 b]pyridine, carcinogens present in cooked beef. AB - During the cooking of beef, the genotoxic heterocyclic aromatic amines 2-amino 3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5 f]quinoxaline (DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are formed. Little is known about the fate of these compounds in humans or the factors affecting it. We have developed assays based on capillary column gas chromatography-negative ion mass spectrometry capable of the simultaneous measurement of MeIQx, DiMeIQx, and PhIP in cooked meat and in human urine using stable isotope labeled analogues. Ten normal, healthy male volunteers were invited to consume a standard cooked meat meal (400-450 g lean beef, cooked as patties on a griddle hotplate) on four separate occasions over a period of 14 months. Following consumption of the test meals, urine was collected from 0 to 8 h, during which time all free amines were excreted and analyzed for MeIQx, DiMeIQx, and PhIP. Subjects ingested 240 +/- 9 (SEM) g cooked meat, which contained 2.2 +/- 0.2 ng MeIQx/g meat, 0.7 +/- 0.1 ng DiMeIQx/g meat, and 16.4 +/ 2.1 ng PhIP/g meat. The variability in relative systemic bioavailability was assessed from the percentage of ingested amine excreted unchanged in the urine. Subjects excreted 2.1 +/- 1.1% of MeIQx and 1.1 +/- 0.5% of PhIP ingested as unchanged amine in the urine. Levels of DiMeIQx in urine, if present, were below the sensitivity of our assay (20 pg/ml) and could not be detected in any of the samples analyzed. Irrespective of dose, urinary excretion of unchanged MeIQx or PhIP (expressed as a percentage of the ingested dose) remained constant for each individual subject. The intraindividual coefficients of variation for MeIQx (28.4%) and PhIP (23.7%) were low and the pooled interday (intrasubject) coefficients of variation for both compounds were only 19 and 3.4%, respectively. In contrast, inter-subject (intraday) variation was greater, with pooled coefficients of variation of 145% for MeIQx and 71% for PhIP. Based on these studies, it should be possible to use the percentage excretion of MeIQx and PhIP to assess the relative bioavailability of these compounds in humans. PMID- 1423265 TI - Clonal rearrangement of chromosome band 6p21 in the mesenchymal component of pulmonary chondroid hamartoma. AB - Pulmonary chondroid hamartomas (PCH) are biphasic benign tumors that contain both mesenchymal and epithelial populations. In this report we describe two PCH in which clonal translocations at chromosome band 6p21 were demonstrated in mesenchymal cells. One of these had a unique translocation, t(6;14)(p21;q24), that was also found in one of two PCH karyotyped previously. The t(6;14) has not been described in other varieties of benign or malignant neoplasia. The 6p21 aberrations are of particular interest because break points in this chromosomal region appear to be characteristic of endometrial polyps. Endometrial polyps, like PCH, are biphasic benign tumors in which mesenchymal clonality has been demonstrated. PMID- 1423266 TI - Retroviral vector-mediated lymphokine gene transfer into human renal cancer cells. AB - Effective vaccination against cancer, either for prophylaxis or therapy, has been an elusive goal for years. Cytokine gene therapy offers a novel approach to generate immunogenic tumor cell vaccines. To examine the feasibility of cytokine gene transfer into human renal cancer (RC) cells, we introduced the cDNAs for human interleukin-2 (IL-2) or interferon-gamma (IFN-gamma) into various RC cell lines with retroviral vectors. Using the NIH3T3 amplification assay, no replication competent retroviral particles were detectable in cell culture supernatants taken from gene-modified RC cell lines. Efficient expression of both lymphokines was achieved. Depending on the cell line and the vector construct used, lymphokine gene-modified human RC cell lines released 4 to 29 units/10(6) cells of IL-2, or up to 10 units/10(6) cells of IFN-gamma within 48 h. Fluorescence-activated cell sorter analysis of SK-RC-29 cells releasing IFN-gamma showed increased expression of major histocompatibility complex class I antigen, beta 2-microglobulin, and ICAM-1, as well as induction of major histocompatibility complex class II antigen expression [human leukocyte antigen(HLA)-DR, -DP], but no changes in these cell surface markers were observed with SK-RC-29 cells releasing IL-2. Following in vitro gamma-irradiation with 5,000 or 10,000 rad, growth of lymphokine gene-modified RC cells was abrogated, but their capability to release lymphokine and express lymphokine-induced antigenic determinants, such as HLA-DR, was retained. Tumor formation by the human RC cell line SK-RC-29 in BALB/c nude mice was not affected by IFN-gamma secretion, but was inhibited by in vivo release of IL-2 from s.c. injected tumor cells. These studies demonstrate the feasibility of retroviral mediated lymphokine-gene transfer into human RC cells and suggest a means for generating autologous or HLA-matched allogeneic tumor cell vaccines for the treatment of patients with renal cell carcinoma. PMID- 1423267 TI - Cytochrome P-450 3A4 (nifedipine oxidase) is responsible for the C-oxidative metabolism of 1-nitropyrene in human liver microsomal samples. AB - The nitrated polycyclic aromatic hydrocarbon 1-nitropyrene is a ubiquitous environmental pollutant. The role of cytochromes P-450 in the human metabolism of [3H]-1-nitropyrene was investigated using human liver microsomes. The range of microsomal metabolism from 16 individual liver specimens was 0.13 to 0.99 nmol/min/mg protein. Using 3 microsomal samples exhibiting different maximal velocities, the Km of 1-nitropyrene metabolism was 3.3 +/- 0.5 microM, indicating that perhaps a single or similar cytochromes P-450 was involved in the metabolism of 1-nitropyrene in these samples. The P-450 3A inhibitor triacetyloleandomycin inhibited 86 +/- 8% of the microsomal metabolism of 1-nitropyrene. Further evidence for the role of P-450 3A in human microsomal metabolism of 1-nitropyrene was gained using inhibitory anti-P-450 3A antibodies. Using 3 separate microsomal samples, antibody conditions that inhibited approximately 90% of the metabolism of the P-450 3A4-specific substrate nifedipine inhibited approximately 60-70% of the metabolism of 1-nitropyrene. Human liver microsomes demonstrated a preference for 1-nitropyren-3-ol formation over 1-nitropyren-6-ol or 1-nitropyren-8-ol, which is in contrast to that noted in rodents where the 6-ol and 8-ol are preferentially formed over the 3-ol, yet in agreement with earlier studies on the metabolism of 1-nitropyrene using Vaccinia-expressed human cytochromes P-450. These results indicate that the human hepatic metabolism of 1-nitropyrene is carried out by at least two or more P-450s including those in the P-450 3A subfamily. These studies also suggest that the metabolism of this compound by humans may differ from that in rodents in both the cytochromes that are involved and the specific metabolites that are formed. PMID- 1423268 TI - Elevated uptake of low density lipoproteins by human lung cancer tissue in vivo. AB - In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. Previous in vitro and in vivo studies have shown that acute myelogenous leukemia cells have elevated receptor-mediated uptake of low density lipoproteins (LDL), compared to normal WBC. High receptor-mediated uptake of LDL by certain cancer cells in tissue culture and experimental tumors in animals in vivo has also been demonstrated. The present study was undertaken to compare the in vivo assimilation of LDL by human lung cancer tissue with that by surrounding lung tissue. Ten patients with newly diagnosed lung tumors, scheduled for surgery, received an i.v. injection of [14C]sucrose-labeled LDL. Following cellular uptake and degradation of the LDL particle, the radiolabeled sucrose moiety remains trapped in the lysosomal compartment, making this labeling technique useful for in vivo studies of tissue uptake of LDL. Radioactivity was determined in plasma and in tissue biopsies obtained at surgery 1-3 days after injection. The uptake of radioactivity in lung cancer tissue was elevated (1.5 3.0-fold), compared to surrounding tissue, in 7 of 9 patients with primary lung cancer. The most rapid preoperative disappearance of radioactivity from plasma was found in 2 patients with large tumors exhibiting high LDL uptake, relative to normal lung tissue. These findings support the hypothesis that the selectivity of cytotoxic agents can be enhanced also in nonhematological malignancies by administering the drugs incorporated in LDL particles. PMID- 1423269 TI - An improved fluorometric assay for dosimetry of benzo(a)pyrene diol-epoxide-DNA adducts in smokers' lung: comparisons with total bulky adducts and aryl hydrocarbon hydroxylase activity. AB - An improved high-performance liquid chromatography/fluorometric assay has been established to quantitate the benzo(a)pyrene (BP) tetrols released after acid hydrolysis of lung DNA from lung cancer patients, so that the formation of benzo(a)pyrene diol-epoxide-DNA adducts can be measured. The r-7,c-10,t-8,t-9 tetrahydroxy-7,8,9,10-tetrahydro-BP isolated by high-performance liquid chromatography was determined by chromatography in two different solvent systems and fluorescence spectroscopy. This assay has a detection limit of 2 pg of r-7,c 10,t-8,t-9-tetrahydroxy- 7,8,9,10-tetrahydro-BP, requires 100-500 micrograms of DNA, and can measure 1 adduct/10(8) unmodified nucleotides. As this assay does not use immunoaffinity chromatography or solvent extraction, it allows a > 90% recovery of benzo(a)pyrene diol-epoxide-DNA adducts. This procedure has been tested on 13 DNA samples prepared from nontumorous lung parenchyma taken from lung cancer patients at surgery and revealed the presence of DNA adducts of the anti-benzo(a)pyrene diol-epoxide in 9 of 11 samples from smokers and in 2 of 2 ex smokers. In only two samples from smokers the formation of adducts derived from syn-benzo(a)pyrene diol-epoxide was detected. A 15-fold variation in DNA adduct level was found in 11 of 13 DNA samples, with a range of 0.6-9.9 adducts of benzo(a)pyrene diol-epoxide/10(8) nucleotides. In samples containing both anti- and syn-benzo(a)pyrene diolepoxide-DNA adducts, the anti/syn adduct ratio is 2:1. A highly significant correlation was found between pulmonary microsomal aryl hydrocarbon hydroxylase activity and the level of benzo(a)pyrene diolepoxide-DNA adduct (r = 0.91; P < 0.001; n = 13). A crude linear correlation between the amounts of these adducts and those of bulky DNA adducts determined by 32P postlabeling assay was observed in the same samples (r = 0.78; P < 0.02; n = 13). Thus this highly sensitive and specific procedure is suitable for measuring benzo(a)pyrene diolepoxide-DNA adducts in human tissues from environmentally exposed subjects and could be adapted to measure polycyclic aromatic hydrocarbons other than BP. PMID- 1423270 TI - Eradication of hepatic metastases of carcinoma H-59 by combination chemoimmunotherapy with liposomal muramyl tripeptide, 5-fluorouracil, and leucovorin. AB - We have investigated the effect of a combined chemoimmunotherapy protocol with liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE), 5-fluorouracil (5 FU), and 5-formyltetrahydrofolate (leucovorin) on the growth of hepatic metastases using carcinoma H-59, a liver-homing subline of the Lewis lung carcinoma (P. Brodt, Cancer Res., 46: 2442-2448, 1986). C57BL/6 mice inoculated with the tumor cells via the intrasplenic route received three i.v. injections of liposomal MTP-PE, the first of which was administered 3 days prior to tumor cell inoculation. Chemotherapy with 5-FU and leucovorin at the maximal tolerated doses (30 mg/kg per injection) was initiated immediately after tumor inoculation and continued on alternate days for a total of 4 injections. The incidence of liver metastases in animals which received the combined therapy was compared to that in animals treated with chemotherapy or immunotherapy alone. We found that while the number of liver metastases was reduced in all of the treatment groups as compared to control untreated or placebo-treated animals, the combined effect of 5-FU leucovorin and liposomal MTP-PE was significantly better than that of chemotherapy or immunotherapy alone. This was reflected in a reduced incidence (70% as compared to 100% in all other groups) and in a significant reduction in the number and size of the liver nodules. Our results suggest that the efficacy of 5-FU and leucovorin in the treatment of hepatic metastases could be significantly augmented by the addition of the liposome-encapsulated immunoadjuvant MTP-PE. PMID- 1423271 TI - Endogenous tumor necrosis factor functions as a resistant factor against hyperthermic cytotoxicity. AB - One of the mechanisms of cytotoxicity by tumor necrosis factor (TNF) is the induction of reactive oxygen molecules. Cells producing endogenous tumor necrosis factor (enTNF) show resistance to the cytotoxicity of exogenous TNF by scavenging the reactive oxygen molecules. The intracellular hydroxyl radical production is also known to be involved in the heat-induced cytotoxicity. In the present study, we therefore examined the possibility that enTNF may act as a protective protein against the heat-induced cytotoxicity in a manner similar to that of exogenous TNF. Heat-sensitive L-M (mouse tumorigenic fibroblast) cells, originally expressing no enTNF, were transfected with a human TNF expression vector to produce enTNF. The stable transfectants showed apparent resistance to heat treatment. Conversely, when HeLa (human uterine cervical cancer) cells, originally producing an appreciable amount of enTNF, were transfected with an antisense TNF mRNA expression vector to inhibit enTNF synthesis, their heat sensitivity was enhanced. Furthermore, L-M cells which were transfected with nonsecretory human TNF expression vector also acquired resistance to heat treatment. In these cells, heat resistance correlated well with expression of enTNF and intracellular levels of manganous superoxide dismutase. These results indicate that enTNF exerts its intracellular protective effect against the heat induced cytotoxicity by scavenging reactive oxygen with induced manganous superoxide dismutase in a manner similar to that found in cells treated with exogenous TNF. PMID- 1423272 TI - Membrane lipid modification and sensitivity of leukemic cells to the thioether lipid analogue BM 41.440. AB - Since the ether lipid anticancer drugs are membrane targeted, we examined the effect of membrane lipid structural alteration on their cytotoxicity. Enrichment with docosahexaenoic acid increased the sensitivity to the thioether lipid BM 41.440, compared to control cells enriched with oleic acid. The effect was dependent upon drug concentration, time, and the extent of cellular fatty acid enrichment. Other polyunsaturated fatty acids had a similar effect, which was proportional to the degree of unsaturation of the molecule inserted. Depletion of cellular glutathione with buthionine sulfoximine increased the sensitivity to ether lipid, but prooxidants such as Fe2+ and antioxidants such as vitamin E had little effect. The addition of serum to the incubation medium markedly diminished the cytotoxicity of ether lipids for cells modified with both docosahexaenoic acid and oleic acid, probably due to binding of the drug to serum components. The toxicity of another ether lipid, 1-O-octadecyl-2-O-methyl-rac-glycero-3 phosphocholine, was not affected appreciably by membrane alteration. Drug uptake studies with a radiolabeled BM 41.440 analogue, 1-[3H]hexadecylthio-2-ethyl-rac- glycero-3-phosphocholine, demonstrated no difference in transport at early time points and no difference in accumulation up to 60 min. We conclude that increases in cellular and/or membrane fatty acid polyunsaturation heighten the cytotoxic effect of a membrane-active ether lipid. The effect is not due to a change in drug transport or accumulation. It may be related to a change in oxidative events. These observations provide further confirmation of the membrane being the target of ether lipid action, using biochemical rather than morphological techniques. Most importantly, this observation offers a potential innovative approach to therapy. PMID- 1423273 TI - Potentiation of the activity of 1-beta-D-arabinofuranosylcytosine by the protein kinase C activator bryostatin 1 in HL-60 cells: association with enhanced fragmentation of mature DNA. AB - We have examined the interaction between 1-beta-D-arabinofuranosylcytosine (ara C) and the macrocyclic lactone protein kinase C activator bryostatin 1 in the human promyelocytic leukemia cell line HL-60. Preexposure of cells to 10 nM bryostatin 1 for 24 h, followed by an additional 24-h incubation with 10 microM ara-C, resulted in greater than additive inhibitory effects toward clonogenic HL 60 cells. In a series of alkaline elution assays, cells preincubated with bryostatin 1 and prelabeled with [3H]thymidine exhibited a significant increase in DNA fragmentation following exposure to ara-C in comparison to cells exposed to ara-C alone. This increase in DNA damage was apparent at both neutral and alkaline pH and was not protein associated. In contrast, studies using cells pulse-labeled with [3H]thymidine immediately before analysis suggested that bryostatin 1 pretreatment did not increase the ability of ara-C to interfere with DNA replicative intermediates. Additional studies demonstrated that the increase in DNA fragmentation induced by bryostatin 1 and ara-C preceded both loss of cell membrane integrity (as determined by trypan blue exclusion) as well as depletion of intracellular ATP and NAD pools. Furthermore, the enhanced inhibitory effects of bryostatin 1 and ara-C toward clonogenic HL-60 cells did not appear to result from the induction of cellular differentiation. Finally, agarose gel electrophoresis of DNA obtained from cells exposed to both bryostatin 1 and ara-C revealed a pattern of integer multiples of 180- to 200-base pair fragments commonly associated with endonucleolytic cleavage; the extent of this fragmentation was considerably greater than that observed in cells exposed to ara C alone. Taken together, these findings suggest that exposure of HL-60 cells to bryostatin 1 renders them more susceptible to ara-C-related DNA damage and that this phenomenon contributes to the cytotoxic effects of this drug combination. They also raise the possibility that bryostatin 1, perhaps through modulation of intracellular signaling events in leukemic cells, has the capacity to potentiate ara-C-related apoptosis or programmed cell death. PMID- 1423274 TI - Renal cell carcinoma and natural killer cells: studies in a novel rat model in vitro and in vivo. AB - The transplantable rat kidney carcinoma (RKC) provides an excellent experimental model for immunological and therapeutic studies of renal cell carcinoma. In this report, we define the biological characteristics of RKC and explore the interactions between RKC and natural killer (NK) cells. RKC, a transplantable tumor of spontaneous origin, grows progressively over a 12-week period and metastasizes to the lung when implanted orthotopically in the kidneys of female Lewis rats. Rats bearing RKC survived for an average of 10.5 +/- 1.5 (SD) weeks postimplantation. Lung metastases were visible between 7.5 and 8.5 weeks postimplantation, and by 9 to 10 weeks the incidence of metastases reached approximately 67%. Injection of the NK cell-specific monoclonal antibody 3.2.3 depleted Lewis rats of their NK activity for up to 14 days. Adherent lymphokine activated killer cells generated from the spleens of 3.2.3-injected rats were significantly less lytic than those from control rats and contained a significantly lower percentage of 3.2.3+ cells when analyzed by flow cytometry. Groups of rats were implanted with RKC and received injections of 3.2.3 biweekly to maintain depletion of NK cells or of a control antibody, NK1.1, specific for mouse NK cells. At 10 weeks postimplantation, 3.2.3-injected rats had significantly (P < or = 0.005) larger tumors (104.4 +/- 20.1 g) than NK1.1 injected rats (75.4 +/- 13.9 g). Spleen cells and peripheral blood cells from uninjected, tumor-bearing rats had a slight but nonsignificant decrease in NK activity against 51Cr-labeled YAC-1 targets over the course of RKC progression. The activity of adherent lymphokine-activated killer cells from tumor-bearing rats was lower than that from normal rats, but not significantly. Cultured RKC cells were killed by both splenic NK cells and adherent lymphokine-activated killer cells. These data demonstrate that RKC is NK sensitive and that tumor growth does not abrogate NK activity. The RKC tumor provides a model system for the analysis of immunological factors in renal cell carcinoma growth and presents opportunities for testing therapeutic interventions in a system that closely mimics the human disease. PMID- 1423275 TI - Tumors arising in SCID mice share enhanced radiation sensitivity of SCID normal tissues. AB - We addressed the question of whether cancers arising in an abnormally radiation sensitive normal tissue are also abnormally sensitive to ionizing irradiation. Germ line mutation-carrying mice with an enhanced radiation sensitivity of the normal tissue, the severe combined immunodeficient (SCID), and normally radiation sensitive mice (C3H) were used to study the sensitivity of normal and tumor tissues in vivo and in vitro. The lethal dose for 50% of the irradiated animals after single dose whole body irradiation was 2.6-fold higher in C3H compared to SCID mice. The dose for an isoeffective acute skin reaction after single dose irradiation was end point dependent 1.7 to 3.7 times higher in C3H than in SCID mice. Embryonic fibroblast and methylcholanthrene induced soft tissue sarcomas derived from C3H and SCID mice were established in vitro and colony-forming assays after single dose irradiation were carried out. Choosing mean inactivation dose as the end point, SCID fibroblast lines were 3.0-fold and SCID tumor cell lines 2.7-fold more radiation sensitive than C3H fibroblast lines and C3H tumor cell lines. Tumor control and growth delay assays for 110-mm3 tumors were used to compare the radiation sensitivity of SCID and C3H tumors in vivo. The doses for 50% local tumor control and a growth delay of 40 days were 2.6 times higher in C3H tumors compared to SCID tumors. Tumors arising in an abnormally radiation sensitive normal tissue are also sensitive to irradiation. The difference in radiation sensitivity of normal tissues predicted the difference in tumor tissues in these two murine systems. PMID- 1423276 TI - Changes in growth and tumorigenicity following reconstitution of retinoblastoma gene function in various human cancer cell types by microcell transfer of chromosome 13. AB - Functional loss of the retinoblastoma (RB) gene has been implicated in the initiation or progression of several human tumor types including cancer of the eye, bone, bladder, and prostate. To examine the consequence of adding one RB allele containing its normal regulatory elements back into representative examples of each of these cancer types, as well as to compare the results to those previously reported using various RB complementary DNA constructs, a neomycin resistant marked 13 chromosome was transferred by microcell fusion. Several attempts to obtain RB positive osteosarcoma cells failed. In addition, only one RB positive retinoblastoma clone was isolated. This clone contained many large cells, could not be maintained in long-term culture, and produced only RB negative tumors. Three RB positive bladder cancer cell clones were obtained, all of which grew slower in culture than their RB negative parental counterpart and did not form colonies in soft agar. Tumorigenicity was markedly suppressed in these clones. One clone yielded no tumors, and the other 2 clones produced only one small tumor each, both of which were RB negative. In contrast, the 2 RB positive prostate cancer cell clones isolated had no differences in their cell culture growth properties, including growth in soft agar compared to the parental cells. One of the clones was nontumorigenic, while the other clone produced 4 small tumors, all of which were RB positive. These results indicate that the transfer of one RB allele by microcell transfer produces different levels of growth inhibition as well as tumor suppression, depending on the cell type examined. In the case of prostate cancer, the function of the RB gene in tumor suppression appears to be independent from its growth regulatory function, since no growth inhibition in cell culture was noted in these cells, although tumor suppression was significant. PMID- 1423277 TI - Local administration of monoclonal antibody-drug conjugate: a new strategy to reduce the local recurrence of colorectal cancer. AB - This report investigates the application of monoclonal antibody A7 and its drug conjugate in locally controlling colorectal cancer. The experimental protocol consisted of local retention, lymphatic delivery, normal organ distribution, systemic toxicity, and tumoricidal effects. When 125I-labeled monoclonal antibody (Mab) A7 was injected into the pelvis and the thigh of Balb/c mice, a high local retention unrelated to antigen-antibody interaction was observed at the injected site for 24 h after injection. An analysis of local retension properties related to antigen-antibody interaction, conducted by intratumorally or peritumorally injecting 125I-Mab A7 into the tumor-bearing athymic nude mice, revealed a significantly higher tumor localization of Mab A7 in comparison to i.v. injection. 125I-Mab A7 accumulated to a great extent in the ipsilateral regional lymph node but not in the contralateral regional lymph node. Normal organ accumulation of Mab A7 was lower in the locally injected group than in the i.v. injected group. Intratumoral injection of Mab A7-neocarzinostatin (A7-NCS) led to the complete remission of established tumor in 5 of 6 antigen-positive xenograft bearing mice but exhibited a complete remission in only 1 of 6 antigen-negative xenograft-bearing mice. A single local injection of A7-NCS inhibited tumor development in 12 of 16 and 5 of 15 antigen-positive tumor-bearing mice and antigen-negative tumor-bearing mice, respectively, whereas neither a systemic injection of A7-NCS and NCS nor a local injection of NCS and saline had a notable inhibitory effect on tumor development. Systemic toxicity of NCS was markedly reduced when it was locally administered in the antibody-conjugated form. These findings indicate that local injection of immunoconjugate is a promising new field for controlling the local recurrence of colorectal cancer. PMID- 1423278 TI - Evidence that a novel human differentiation-inhibiting protein blocks the dimethyl sulfoxide-induced differentiation of erythroleukemia cells by inhibiting the activation of membrane protein kinase C. AB - We have previously reported (J. P. Durkin et al., Blood, 79: 1161-1171, 1992) the isolation of a human differentiation-inhibiting protein (DIP) which selectively inhibits and blocks the differentiation of erythroid burst-forming unit progenitor cells in bone marrow colony assay, and the dimethyl sulfoxide (DMSO) induced differentiation of cultured murine erythroleukemia (MEL) cells. DIP blocks MEL cell differentiation directly, without affecting the ability of the cells to proliferate. In the present study, DIP (at < 1 ng/ml) inhibited MEL cell differentiation only when added to the culture medium within 1 h after DMSO induction, indicating that it blocked an early, critical step in erythroleukemia cell differentiation. The protein kinase C (PKC) inhibitor H-7 also maximally inhibited the differentiation of MEL cells during this same period following induction, suggesting that DIP may have blocked an early PKC-dependent process. Indeed, DIP was found to abolish a transient increase in membrane PKC activity which was triggered in MEL cells within 10-30 min after DMSO addition. This increase in membrane PKC activity resulted from the activation of an inactive pool of PKC residing on membranes, and not from the translocation of cytosolic PKC to membranes. DMSO also stimulated membrane PKC activity and differentiation in human erythroleukemia cells and HL-60 myeloid leukemia cells. As was the case with MEL cells, DIP prevented the early activation of PKC and the differentiation of human erythroleukemia cells. However, it did not inhibit the early increase in PKC activity in HL-60 cells or the subsequent differentiation of these cells. These results suggest that DIP blocks erythroleukemia cell differentiation by inhibiting an early and critical activation of inactive membrane PKC. PMID- 1423279 TI - Myelopoiesis-associated immune suppressor cells in mice bearing metastatic Lewis lung carcinoma tumors: gamma interferon plus tumor necrosis factor alpha synergistically reduces immune suppressor and tumor growth-promoting activities of bone marrow cells and diminishes tumor recurrence and metastasis. AB - Metastatic Lewis lung carcinoma (LLC) tumors stimulate myelopoiesis and, consequently, induce bone marrow cells to become immune suppressive to T cell blastogenesis and macrophage activation for tumor necrosis factor alpha (TNF alpha) secretion. The suppressor cells phenotypically resembled granulocytic monocytic progenitor cells. In order to diminish the presence of these immune suppressor cells, LLC-bearing mice were treated with low doses of gamma interferon (IFN-gamma) (100 units/mouse) plus TNF-alpha (10 units/mouse). Treatment of LLC-bearing mice with these low doses of IFN-gamma plus TNF-alpha diminished the suppressive activity of their bone marrow cells, as measured by the effect on normal macrophage activation to secrete TNF-alpha. In in vivo adoptive transfer studies, bone marrow from placebo-treated LLC-bearers stimulated tumor establishment and metastasis, while the bone marrow of IFN-gamma plus TNF-alpha-treated tumor-bearers diminished LLC establishment and metastasis. The effect of the low dose treatments with IFN-gamma and/or TNF-alpha on the recurrence of excised s.c. tumors was also assessed. Treatment of mice following tumor excision with either IFN-gamma, TNF-alpha, or the combination of IFN-gamma plus TNF-alpha reduced recurrence. However, in the animals with recurring tumors only the combined IFN-gamma plus TNF-alpha treatment effectively diminished the development of lung metastases. These results demonstrate that low dose IFN-gamma plus TNF-alpha treatment diminishes the presence of suppressor and tumor growth promoting activities of bone marrow and reduces tumor recurrence and metastasis. PMID- 1423280 TI - Lipophilic cisplatin analogues entrapped in liposomes: role of intraliposomal drug activation in biological activity. AB - cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II) (NDDP), a lipophilic cisplatin analogue containing two branched leaving groups of 10 carbon atoms, is undergoing clinical evaluation in a liposomal formulation. In previous studies, NDDP entrapped in multilamellar vesicles composed of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) at a 7:3 molar ratio was non-nephrotoxic in humans, not cross-resistant with cisplatin in different in vitro and in vivo systems, and more active than cisplatin against murine models of experimental liver metastases whereas free NDDP was devoid of in vivo antitumor activity at the optimal dose of L-NDDP and barely active at higher doses. To elucidate the mechanisms by which the liposomal carrier enhances the biological properties to this class of antitumor agents, we studied the effect of the liposome composition, size of the branched leaving groups of the platinum compound, and pH and composition of the aqueous phase on the entrapment efficiency, drug leakage, drug stability, and in vivo toxicity and antitumor activity of different liposomal formulations of these agents. In experiments using normal saline as aqueous phase, the presence of DMPG in the lipid bilayer resulted in a decreased stability and an increased biological activity of NDDP, whereas NDDP entrapped in liposomes composed of DMPC alone (not containing DMPG) was stable but devoid of antitumor activity. In studies with structurally related analogues with branched leaving groups of 5, 6, 7, and 9 carbon atoms, similar trends were observed. In addition, the number of carbon atoms in the leaving groups was directly and inversely related to the entrapment efficiency and stability of the analogues, respectively, independently of lipid composition; increasing the size of the branched leaving groups resulted in an increased in situ degradation of the platinum compound and enhanced biological activity and potency. These results suggest that this class of platinum compounds exerts its biological activity through the formation of active intermediates in situ within the lipid bilayers and that the activation reaction is highly dependent on the presence of DMPG and the size of the lipophilic leaving group. PMID- 1423281 TI - Intrinsic radiosensitivity of normal human fibroblasts and lymphocytes after high and low-dose-rate irradiation. AB - The existence of heritable radiosensitivity syndromes and clinical observations in radiotherapy patients suggests that human cellular radiosensitivity differs among individuals. We report here an in vitro study of radiosensitivity in 30 fibroblast and 29 lymphocyte cultures obtained from cancer patients and controls. In 25 cases, both fibroblasts and lymphocytes were obtained from the same donors. Fibroblasts were cultured from skin biopsy samples, and peripheral T-cell lymphocytes were cultured from blood. Clonogenic survival assays were performed by using high- and low-dose-rate irradiation; lymphocytes were in G0 phase and fibroblasts in confluent plateau phase. Various end points were calculated and compared (i.e., surviving fraction at 2 Gy, initial slope of the survival curve, and doses resulting in 10 and 1% survival, respectively). Depending on the end point, the coefficient of variation of the survival parameters ranged from 31 to 68% for lymphocytes and 21 to 41% for fibroblasts following high-dose-rate irradiation. Similar ranges were obtained after low-dose-rate irradiation. Variance analysis performed on replicate assays in cultures derived from the same patient showed that variation due to technical or sampling errors was significantly lower than variation between individuals (P = 0.00034 and 0.014 for fibroblasts and lymphocytes, respectively). No correlation was observed between the radiosensitivity of lymphocyte and fibroblast cultures derived from the same donors. We conclude that there is significant variation in normal cell radiosensitivity among individuals. On the other hand, comparisons of lymphocyte and fibroblast radiosensitivities suggest that tissue-specific characteristics, such as differentiation status, may variably modulate radiosensitivity. PMID- 1423282 TI - In vivo effects of high-intensity ultrasound on prostatic adenocarcinoma Dunning R3327. AB - High-intensity ultrasound has been used to treat Dunning R3327 prostatic adenocarcinoma implanted s.c. in Fischer Copenhagen rats. Focused ultrasound was generated with a 1-MHz transducer and energy was provided by a 7.5-kW power amplifier. Seventy-four rats were treated using two different sublines of Dunning tumor. Study 1 dealt with 49 rats with the Mat-Ly-Lu subline, treated with acoustic intensities ranging from 300 to 2750 W/cm2. Of the 49 rats in Study 1, 30 had complete tumor necrosis and 19 had no effect; of the 30 who had complete local tumor necrosis, 14 had local relapse, 9 had distance metastases to lung and nodes without local occurrence, and 7 remained free of tumor and were still alive 12 months after treatment. In Study 2, 25 rats with AT2 subline were treated with an intensity of 820 W/cm2. Similarly for Study 2, there was complete local tumor necrosis in 24 of 25 animals, with local regrowth in 7 of 24 and no recurrence of metastasis in the remaining 16 after a follow-up of 3 months. These results suggested that high-intensity focused ultrasound could be useful for the treatment of small localized cancerous tumors such as low-grade prostate carcinoma. PMID- 1423283 TI - Interstitial hypertension in human breast and colorectal tumors. AB - The efficacy of present day antineoplastic regimens depends upon the delivery and penetration of therapeutic agents through the tumor vascular and interstitial spaces to the tumor cell target. The distribution of relevant molecules or cells in a solid tumor is often poor and heterogeneous and is believed to be due to a number of pathophysiological factors, including elevated interstitial fluid pressure (IFP). Using the wick-in-needle technique, IFP was measured in primary breast and colorectal carcinomas as well as their respective metastases to the lymph nodes and liver in a total of 17 patients. IFP was also measured in one recurrent renal cell carcinoma, one melanoma metastasis to the lymph nodes, and another melanoma metastasis to the lung. IFP varied from 4 to 50 mm Hg with a mean +/- SD of 20 +/- 13 mm Hg in the neoplasms (n = 41 measurements; n = 21 tumors), while IFP in normal tissues had a mean of 2 +/- 4 mm Hg (n = 11). The mean IFPs for metastatic melanoma, primary breast carcinoma, and liver metastases from a colorectal primary were found to be 33 +/- 14, 15 +/- 9, and 21 +/- 12 mm Hg, respectively. In the renal cell carcinoma, the pressure was 38 mm Hg. These results agree with the findings of our 3 previous studies examining IFP in human superficial melanomas (14.3 +/- 12.5 mm Hg, n = 12), cervical carcinomas (15.7 +/ 5.7 mm Hg, n = 12), and head and neck tumors (13.2 +/- 8.8 mm Hg, n = 19), and indicate that in all types of human tumors studied to date, IFP was significantly elevated above that of normal tissue. This observation may be useful in localizing tumors during needle biopsy. PMID- 1423284 TI - Binding of human single-stranded DNA binding protein to DNA damaged by the anticancer drug cis-diamminedichloroplatinum (II). AB - The chemotherapeutic drug cis-diamminedichloroplatinum (II) covalently binds to DNA resulting in a variety of adducts and cross-links which are thought to be responsible for the toxicity of the drug. We have used the gel mobility shift assay to detect proteins which bind to DNA treated in vitro with cis diamminedichloroplatinum (II) and have identified two complexes which bind with increased affinity to cis-diamminedichloroplatinum (II)-damaged DNA. Using monoclonal antibodies we have shown that one complex, B1, contains human single stranded DNA binding protein, a protein known to be involved in the in vitro repair synthesis assay of mammalian excision repair. PMID- 1423285 TI - The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot. AB - Alteration of the p53 gene is the most frequent genetic feature of human cancer and leads to overexpression of the altered protein in the tumor cell nucleus. Two diagnostic procedures are currently available to assess p53 mutations: (a) molecular analysis of the gene sequence; and (b) immunohistochemical analysis of p53 protein accumulation. We now report a third approach, serological analysis. Fifteen % of primary breast cancer patients were found to have circulating antibodies to p53 protein by immunoprecipitation or immunoblotting. We have found a close correlation between the presence of such antibodies and bad prognosis such as high histological grade and the absence of hormone receptors. Furthermore, we found that the B-cell response to p53 protein is induced by two immunodominant regions located at the carboxy and amino termini of the protein, outside the central mutational hot spot region. These findings suggest that serological analysis, combined with molecular and histochemical methods, may be suitable for assessing the state of the p53 gene in cancer patients. PMID- 1423286 TI - Mutations in the p53 gene in radiation-sensitive and -resistant human squamous carcinoma cells. AB - Five of six human squamous cell carcinoma (SCC) cell lines characterized as radiation sensitive (SQ-38, SCC-9, SQ-9G) or radiation resistant (SQ-20B, SCC-35, JSQ-3) exhibited alterations of the p53 gene. The point mutations and a deletion were detected by using single-stranded conformational polymorphism analysis and polymerase chain reaction-direct sequencing. Interestingly, three of three radiation-sensitive and two of three radiation-resistant cell lines revealed mutations in the p53 gene. Point mutations were located in exons 4, 6, and 8 (at codons 72 and 298 in JSQ-3; 273 in SCC-35; 196 in SQ-38), and deletions consisted of 32 base pairs between codons 274 and 285 in SCC-9 and 1 base pair at codon 271 in SQ-9G. Three mutations resulted in substitutions for an arginine residue. Immunocytochemical analysis confirmed p53 protein overexpression in SCC-35 cells which contained a missense mutation at codon 273. In contrast to previous studies which linked alterations in ras, myc, and raf expression with radiation resistance, this study indicates that mutations in the tumor suppressor gene, p53, do not directly correlate with such resistance. PMID- 1423287 TI - Induction of sister chromatid exchanges by extremely low doses of alpha particles. AB - The induction of sister chromatid exchanges (SCE) was examined in Chinese hamster ovary cells irradiated in the G1 phase of the cell cycle with alpha-particles from a plutonium-238 source. A significant increase in the frequency of SCE occurred with doses as low as 0.31 mGy (31 millirads). Although 30% of the cells showed an increased frequency of SCE at this dose, less than 1% of cell nuclei were actually traversed by an alpha-particle. A dose of approximately 2.0 Gy was necessary to produce a similar increase in SCE by X-rays. These results indicate that genetic damage may be induced by low doses of alpha-radiation in cell nuclei not actually traversed by an alpha-particle. This phenomenon may have important implications in the estimation of risks of such exposures. PMID- 1423288 TI - Carcinogen-specific mutational pattern in the p53 gene in ultraviolet B radiation induced squamous cell carcinomas of mouse skin. AB - We have examined 35 epidermal tumors induced in mice of four different strains by chronic exposure to ultraviolet B radiation for the presence of aberrations in the p53 tumor suppressor gene. Polymerase chain reaction products from p53 exons 5 to 8 were screened by single-strand conformation polymorphism analysis and sequencing. Base substitutions were found in seven tumors (20%). All mutations occurred at dipyrimidine sequences; most frequent were C-->T single base and CC- >TT tandem transitions suggesting the involvement of UV radiation in the genesis of the mutations. Three base substitutions were located at codon 148, and all dipyrimidine-derived mutations occurred at sites where the sequence is present in the nontranscribed DNA strand, indicating some site and strand specificity of the ultraviolet B-induced p53 mutations. PMID- 1423289 TI - A comparison of human O6-methylguanine-DNA methyltransferase promoter activity in Mer+ and Mer- cells. AB - The activity of the human O6-methylguanine-DNA methyltransferase (MGMT) gene promoter was determined in eight human cell lines by measuring chloramphenicol acetyltransferase activity in a reporter gene system. MGMT promoter activities in cells that do not express MGMT (Mer-) fell within the range of activities seen in cells that do express MGMT (Mer+). The promoter region contains 11 potential binding sites for the transcription factor Sp1, but no correlation was seen between cellular Sp1 protein and MGMT promoter chloramphenicol acetyltransferase activity. Because Mer- cells are not deficient in the factors needed for transcription of MGMT, we suggest that at least two mechanisms regulate MGMT expression. One suppresses MGMT mRNA and protein in Mer- cells, and another regulates the levels of constitutive expression in Mer+ cells. Sp1 is not a limiting factor in MGMT expression. PMID- 1423290 TI - Differential metabolic patterns of iodinated versus radiometal chelated anticarcinoma single-chain Fv molecules. AB - Genetically engineered single-chain Fvs (sFv) are defined as recombinant proteins composed of a variable light chain amino acid sequence of an immunoglobulin tethered to a variable heavy chain sequence by a designed peptide. Previous studies using iodine-labeled sFv, derived from the anticarcinoma monoclonal antibody CC49, showed that the 125I-sFv could efficiently target antigen-positive tumors in a human tumor xenograft model while demonstrating rapid plasma clearance and minimal uptake in normal organs. One of the issues we raised in the analysis of the iodinated sFv metabolic studies was whether similar metabolic patterns would be observed if the sFv were labeled with a radiometal. In the studies reported here, 125I-CC49 sFv and 177Lu-CC49 sFv were co-injected in mice bearing antigen-positive carcinoma xenografts. Both sFv forms showed similar tumor targeting and plasma clearance pharmacokinetics. The 177Lu-sFv, however, showed a greater uptake in liver and spleen and a much higher uptake in kidney. These studies thus demonstrate that despite their small size (M(r) 27,000), the metal-chelated sFv shows a metabolic pattern very different than that of the iodinated sFv, which is most likely due to retention of the metal by organs metabolizing the sFv. PMID- 1423291 TI - Modulation of subcellular distribution of doxorubicin in multidrug-resistant P388/ADR mouse leukemia cells by the chemosensitizer ((2-isopropyl-1-(4-[3-N methyl-N-(3,4-dimethoxy-beta- phenethyl)amino]propyloxy) benzenesulfonyl))indolizine. AB - The impact of the novel chemosensitizer ((2-isopropyl-1-(4-[3-N-methyl-N-(3,4 dimethoxy-beta- phenethyl)amino]propyloxy)benzenesulfonyl))indolizine (SR33557) on the intracellular distribution of doxorubicin (DOX) within the multidrug resistant murine P388/ADR leukemia cell line was studied by fluorescence microscopy. We found that under conditions which modulated multidrug-resistant (30 microM SR33557 for 1 h), P388/ADR cells presented an original sequestration of DOX in large intracellular vesicles, where SR33557 is itself sequestered, as seen by colocalization studies. Colocalization experiments with lysosomal and mitochondrial probes suggest that these vesicles are neither mitochondrial in nature nor functional lysosomes. To investigate the biochemical basis for this effect, we studied the impact of SR33557 on the sphingolipid metabolism of P388/ADR cells. We observed that although P388/ADR cells normally catabolized exogenous [3H]sphingomyelin, when pretreated with SR33557 they showed almost complete inhibition of sphingomyelin breakdown. Finally, in order to demonstrate that the inability of P388/ADR cells to degrade sphingomyelin in the presence of SR33557 (which is a potent inhibitor of acid lysosomal sphingomyelinase) leads to phospholipid accumulation, we performed electron microscopy where we observed laminated inclusions. These morphological modifications are similar to those observed in Niemann-Pick disease lymphoblastoid cell lines which are inherently deficient in acid sphingomyelinase activity. The observation that, in the absence of SR33557, these Niemann-Pick disease cell lines presented similar DOX sequestration to that of SR33557-treated P388/ADR cells strongly suggests that DOX accumulates in SR33557-induced myeloid bodies. The redistribution of DOX within these vesicles, perhaps by preventing its expulsion by P-glycoprotein, may be a key in discovering the mechanism of action of SR33557. PMID- 1423292 TI - Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor 1. AB - The activation of the insulin-like growth factor 1 (IGF-1) receptor by its ligand plays a central role in the growth of most cell types. We have used the techniques of computational chemistry in order to design and synthesize several novel analogues of IGF-1. These analogues were able to inhibit the autophosphorylation of the IGF-1 receptor as well as the growth of several different cell types, including prostate carcinoma cells and SV40-transformed cells. Additionally, we have found that D-amino acid analogues of these peptides are apparently resistant to the proteolytic degradation that occurs in the presence of whole sera. Consequently, these analogues seem to show great potential both as probes of the structure/function activities of the IGF-1 signalling pathway and as novel clinical strategies in controlling abnormal cellular growth. PMID- 1423293 TI - Effects of cancer immunotherapy with indomethacin and interleukin-2 on murine hemopoietic stem cells. AB - We examined: (a) whether in vitro-generated lymphocyte-activated killer (LAK) cells from normal mice and splenic killer cells from tumor-bearing mice subjected to interleukin-2 (IL-2) therapy alone or in combination with chronic indomethacin therapy have any detrimental effects on the spleen colony-forming units (CFU-S) of the normal bone marrow (BM); and (b) the effects of these immunotherapy protocols on CFU-S numbers in host hemopoietic organs. Effects of in vitro generated LAK cells (normal C3H/HeN mouse splenocytes cultured with 1000 units IL 2/10(6) cells for 72 h) on BM CFU-S were examined by incubating macrophage depleted BM cells with LAK cells at 1:2.5 and 1:5 BM:LAK cell ratios or with LAK cell supernatant for 4 h. The cells were washed and subsequently injected into irradiated mice. Irradiated mice were also reconstituted with BM cells or LAK cells incubated alone. Spleen colonies were scored macroscopically and microscopically on day 7 after reconstitution of lethally irradiated mice with the various cell combinations. A comparison of colony numbers produced by LAK and BM cell mixture revealed that LAK cells at either dose had no suppressive effect on the colony-forming ability of BM at the macroscopic and microscopic levels of analysis. The supernatant of cultured LAK cells had a minor suppressive effect on colony formation at the macroscopic but not the microscopic level of analysis, indicating the presence of one or more suppressive factors capable of mediating a short-term inhibitory effect. In the immunotherapy experiment, C3H/HeN mice transplanted s.c. with 5 x 10(5) C3L5 mammary adenocarcinoma cells received either vehicle alone (controls), IL-2 (1.5 x 10(4) Cetus units i.p. every 8 h on days 10-14 and days 20-25), or chronic indomethacin therapy (10 micrograms/ml in drinking water from day 5 onwards) plus IL-2 as above. Animals were killed 24-25 days after tumor transplantation to examine: (a) the number of metastatic lung nodules; (b) the effects of co-incubating therapy-generated splenic effector cells with normal BM cells for 4 h on BM CFU-S, and (c) the CFU-S content of host BM and spleen. Results revealed a drop in spontaneous lung metastases from a mean of 50 in control mice to 18 with IL-2 therapy alone, and to 5 with chronic indomethacin therapy plus IL-2 therapy. Splenocytes from normal and tumor-bearing control or treated mice, when incubated with normal BM, had no effect on spleen colony formation at the macroscopic level.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423294 TI - Expression of the endogenous O6-methylguanine-DNA-methyltransferase protects Chinese hamster ovary cells from spontaneous G:C to A:T transitions. AB - We have investigated whether the presence of a DNA repair enzyme, O6 methylguanine-DNA-methyltransferase (MGMT), affects the nature of spontaneous mutations in a mammalian cell line. We compared spontaneous mutations in the adenine phosphoribosyl transferase gene of a Chinese hamster ovary (CHO) cell line that expressed 14,000 MGMT molecules/cell with those in the parental CHO cells lacking this DNA repair activity. The mutation rate/cell/generation of the two CHO cell lines did not differ significantly. However, DNA sequence analysis of spontaneous mutations in the MGMT-proficient CHO cell line revealed a complex picture. No significant difference from the parental CHO cells was found in the number or type of deletions, frameshifts, multiple substitutions, or insertions. The frequency of G:C to T:A transversions was elevated in MGMT-proficient CHO cells. Expression of the enzyme considerably reduced G:C to A:T transitions (25% versus 8.3%). This latter result is the first evidence that this protein is active on an endogenous source of O6-methylguanine that is normally responsible for spontaneous G:C to A:T transition mutations. PMID- 1423295 TI - Therapy with unlabeled and 131I-labeled pan-B-cell monoclonal antibodies in nude mice bearing Raji Burkitt's lymphoma xenografts. AB - Clinical trials of radioimmunotherapy (RIT) of lymphoma have produced frequent tumor regressions and remissions, but it has been difficult to determine to what extent these tumor responses have been due to antibody-specific targeted radiation, nontargeted radiation, and/or cytotoxicity mediated by the carrier monoclonal antibody (MoAb). In this report, RIT was studied in athymic nude mice bearing s.c. Raji human Burkitt's lymphoma xenografts using two different pan-B cell MoAbs, MB-1 (anti-CD37) and anti-B1 (anti-CD20), which differ in isotype (and thus the potential for interaction with host effector mechanisms) and isotype-matched control antibodies either in the unlabeled state or labeled with 131I. When a single i.p. injection of 300 microCi 131I-labeled MB-1 (IgG1) was compared to treatment with unlabeled MB-1 or 300 microCi 131I-labeled MYS control IgG1 MoAb, an antibody-specific targeted radiation effect of RIT was seen. 131I labeled MB-1 produced a 44 +/- 19% (SEM) reduction in tumor size at 3 weeks posttreatment, while unlabeled MB-1 or 300 microCi 131I-labeled MYS control IgG1 antibody treatment resulted in continued tumor growth over this period of time. In vitro studies demonstrated that MB-1 was incapable of mediating antibody dependent cellular cytotoxicity using Raji tumor cell targets and human peripheral blood mononuclear cells. Similar to the MB-1 studies, treatment with 300 microCi 131I-labeled anti-B1 produced a 64% reduction in mean tumor size, while 300 microCi of control antibody resulted in a 58% increase in tumor size over the same 3-week period. In contrast to MB-1, however, unlabeled anti-B1 (an IgG2a MoAb which in vitro studies showed to be capable of antibody-dependent cellular cytotoxicity) also had a substantial antitumor effect. Indeed, 300 microCi 131I-labeled anti-B1 and unlabeled anti-B1 treatment (using an equivalent amount of total protein in the treatment dose) produced a similar specific reduction in tumor size. Increasing the radionuclide dose of anti-B1 to 450 microCi in another experiment did not produce a significant difference in tumor regression compared to a 300-microCi dose. These results suggest that the antitumor effects of 131I-labeled anti-B1 treatment were dominated by antibody mediated cytotoxicity mechanisms, such that an antibody-specific targeted radiation effect could not be distinguished. In contrast, antibody-specific targeting of radiation was the dominant mechanism of tumor killing with 131I labeled MB-1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423296 TI - Inhibition by 5-fluorouracil of cis-diamminedichloroplatinum(II)-induced DNA interstrand cross-link removal in a HST-1 human squamous carcinoma cell line. AB - To elucidate the mechanism of the synergistic cytotoxicity of 5-fluorouracil (5 FU) and cis-diamminedichloroplatinum(II) (CDDP), we studied the interaction of these agents using a human squamous carcinoma cell line (HST-1). Exposure to 5-FU for 24 h and to CDDP for 1 h produced a 50% inhibitory concentration of 1.0 micrograms/ml (7.7 microM) and 2.5 micrograms/ml (8.3 microM), respectively. The cytotoxic action of CDDP was augmented, and a greater than additive effect was observed when the cells were exposed to 5-FU (1.0 micrograms/ml; 7.7 microM) for 24 h before the CDDP treatment. This synergistic activity was maximal when the interval between 5-FU and CDDP exceeded 24 h. In contrast, the cytotoxicity of CDDP was attenuated when it preceded the exposure to 5-FU. Thymidine did not alter the 5-FU-CDDP interaction. Evaluation of the kinetics of the removal of DNA interstrand cross-links, measured by alkaline elution, showed a significant reduction of this removal in the cells exposed to 5-FU followed by CDDP with a drug-free interval of 48 h, as compared with cells exposed to CDDP alone, or to 5 FU immediately followed by CDDP, although no differences were found in the formation of DNA interstrand cross-links by CDDP among these cells. No significant differences in the accumulation of intracellular platinum were detected by atomic absorption spectrophotometry. These findings suggest that 5-FU modulates the repair of platinum-DNA adducts, thereby potentiating the antitumor activity of CDDP. PMID- 1423297 TI - T-cell subset analysis of Lewis lung carcinoma tumor rejection: heterogeneity of effectors and evidence for negative regulatory lymphocytes correlating with metastasis. AB - We have analyzed the phenotypes of the T-cell subsets generated in response to Lewis lung carcinoma clones in C57BL/6J recipients. The metastatic derivative, which expresses low levels of H-2Kb gene, predominantly elicited CD8, V beta 8, and V beta 9+ T-cells. The nonmetastatic clone expressing high levels of H-Kb gene triggered a more heterogeneous response of V beta-5, -6, -8, -9, and -11 CD8+ T-cells. Comparison of the T-cell receptor (TCR) expression of the T-cells infiltrating the tumor site with the lymphocytes in the periphery of tumor bearing animals revealed a pattern of homing of CD4+ T-cells bearing V beta-5, 6, and -11 TCR chains and CD8+ T-cells bearing V beta-5, -6, -9, and -11. Depletion of V beta 5 or V beta 6+ T-cells correlated with accelerated tumor growth, implying their protective role as tumor-specific effectors and consistent with the cytotoxicity of T-cells with this TCR phenotype. V beta 11 TCR expression in the tumor-infiltrating lymphocytes increased with the tumor size. Depletion of V beta 11+ T-cells enhanced resistance to primary tumor growth and conferred protection from metastasis in recipients cleared of V beta 5 and V beta 6 T-cell subsets. Those results suggest that tumor-specific effectors as well as negative regulator T-cells home, infiltrate, and coexist in the tumor site. PMID- 1423298 TI - Induction of c-fos gene expression by exposure to a static magnetic field in HeLaS3 cells. AB - Effects of a static magnetic field on cell growth and c-fos oncogene expression were investigated. HeLaS3 cells exposed to the magnetic field of 0.18-0.2 T for 1 6 days were not affected in the cell growth. Exposure to the magnetic field did not enhance the effects of X-rays or heat treatment which caused the transient cell growth delay. c-fos mRNA in the HeLaS3 cells was undetectable in untreated cells, but the expression was induced in cells by the magnetic field exposure for 2-24 h. The amounts of the mRNA expression changed time dependently with a peak at a 6-h exposure. c-fos was expressed following the heat treatment at 45 degrees C for 10 and 15 min, and the expression was further enhanced by the treatment of cells with heating followed by 4 h of the magnetic field exposure. Exposure of the cells to a static magnetic field may affect some cellular metabolic events leading to the c-fos gene expression. PMID- 1423299 TI - Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers. AB - Loss of heterozygosity occurring on various chromosomes has been described in the majority of human tumors. The targets of frequent or consistent subchromosomal deletions are believed to be tumor suppressor genes. We examined 72 esophageal tumors (46 squamous cell carcinomas and 26 adenocarcinomas) for loss of heterozygosity at the p53, Rb, APC, MCC, and DCC loci. Inclusion of these tumor suppressor genes in the allelic deletions was directly ascertained by performing polymerase chain reaction at polymorphic sites within the genes. Loss of heterozygosity occurred in 55% of informative cases at p53, in 48% of informative cases at Rb, in 66% at APC, in 63% at MCC, and in 24% at DCC. Ninety-three % of tumors informative at all loci (fully informative) lost heterozygosity of at least one locus. A high percentage of fully informative tumors (71%) also lost heterozygosity at more than one locus. There were no significant differences among histological types in the prevalence of loss of heterozygosity at any locus. There were correlations of losses involving MCC versus DCC, Rb, and p53. These data suggest that (a) allelic deletions including these tumor suppressor genes are important in the formation and/or progression of most esophageal cancers; (b) allelic deletions involving MCC may not occur independently of deletions involving other tumor suppressor genes; and (c) the accumulation of multiple allelic deletions involving specific tumor suppressor genes may be important in most esophageal tumorigenesis or tumor evolution. PMID- 1423300 TI - Estrogenic potential of progestins in oral contraceptives to stimulate human breast cancer cell proliferation. AB - Most oral contraceptives (OC) contain a progestin in combination with an estrogen, and the progestin component in OC includes one of the following 19 nortestosterone derivatives: norethynodrel; norethindrone; or norgestrel (levonorgestrel). It is well known that estrogens promote the growth of breast cancer. However, progestins have recently also been implicated in the development of breast cancer. We have compared and contrasted the ability of synthetic progestins to stimulate the proliferation of cultured human breast cancer cells and examined their possible mechanism of action. We found that some progestins used in OC were able to stimulate the growth of estrogen receptor-positive (ER+) MCF-7 and T47DA18 human breast cancer cells but not ER- MDA-MB-231, BT-20, and T47DC4 human breast cancer cells. However, two other progestins, MPA and R5020, which are not used in OC, were either not able to stimulate or only slightly stimulated growth. The potency of norethynodrel [median effective dose (EC50) = 4 x 10(-8) M] and norethindrone (EC50 = 3 x 10(-8) M) was greater than norgestrel (EC50 = 2 x 10(-7) M) in MCF-7 cells. E2 (EC50 = 8 x 10(-13) M) was an even more potent stimulator of growth. More importantly, the progestin-induced growth stimulation was blocked by the antiestrogens 4-hydroxytamoxifen and ICI 164,384 but not the antiprogestin 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)-17 alpha-(1-propynyl)-estra-4, 9-dien-3-one (RU486). To determine whether the proliferative action of progestins was mediated through the ER, cells were transfected with a chloramphenicol acetyltransferase reporter gene containing an estrogen response element derived from vitellogenin 2A gene. The progestins which stimulated the growth of breast cancer cells also increased chloramphenicol acetyltransferase activity. The induction of chloramphenicol acetyltransferase activity was blocked by the addition of the antiestrogens 4-hydroxytamoxifen and ICI 164,384 but not the antiprogestin RU486. This study provides direct evidence that the 19-nortestosterone derivatives in OC have estrogenic properties and suggests that activation of ER, but not progesterone receptor, is the growth stimulatory mechanism for these synthetic progestins. Our results may help to explain the conflicting evidence linking OC and breast cancer risk. A rigorous evaluation of the "total" estrogenic potential of OC might produce a better correlation with breast cancer risk. PMID- 1423301 TI - HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy. AB - Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor infiltrating lymphocytes (TILs) (86), alpha-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL 2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy. PMID- 1423302 TI - Comparison of mouse and human colon tumors with regard to phase I and phase II drug-metabolizing enzyme systems. AB - Since human colorectal tumors are insensitive to most chemotherapeutic agents, there is a need for the discovery of new drugs that would show activity against this disease. In an attempt to better appreciate the relevance of a widely used mouse colon tumor (colon adenocarcinoma Co38) as a screening model for human colorectal tumors, we compared the main phase I and phase II drug-metabolizing enzyme systems in both tumoral and nontumoral colon tissues. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B2, 2C, 2E1, and 3A), epoxide hydrolase, and glutathione-S-transferases (GST-alpha, -mu, and pi). The activities of the following enzymes or cofactors were determined by spectrophotometric or fluorometric assays: total cytochrome P-450, 1-chloro-2,4 dinitrobenzene-GST, selenium-independent glutathione peroxidase, 3,4 dichloronitrobenzene-GST, ethacrynic acid-GST, total glutathione, epoxide hydrolase, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. Results obtained by Western blot showed that mouse colon adenocarcinoma Co38 did not express any of the probed cytochromes P-450, whereas human colorectal tumors expressed only low levels of cytochrome P-450 3A. GST alpha and GST-pi were detected in all tumoral and nontumoral tissues of both species. The neutral GST-mu was expressed in all murine tissues investigated and was found to be polymorphic in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzyme levels, whereas mouse colon adenocarcinoma Co38 had a lower expression of GST-mu and GST-pi, compared to normal mouse colon. Enzymatic activities for glutathione peroxidase, 3,4-dichloronitrobenzene-GST, and ethacrynic acid-GST confirmed the Western blot results for GST-alpha, GST-mu, and GST-pi, respectively. Total GSH levels were similar between murine and human tumors but were 3-fold higher in human tumors than in peritumoral tissues, whereas they were 7-fold lower in mouse colon tumor Co38, compared to normal mouse colon. Epoxide hydrolase was not expressed in either mouse colon adenocarcinoma Co38 or normal mouse colon tissues, whereas it was expressed in human colon peritumoral and tumoral tissues at similar levels. No significant difference was observed between human tumors and peritumoral tissues for UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. For murine colon tissues, the conjugation pathways (UDP-glucuronosyltransferase and sulfotransferase) were lower in colon adenocarcinoma Co38, whereas the converse was observed for the corresponding hydrolytic enzymes (beta-glucuronidase and sulfatase).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423303 TI - Potent preventive action of alpha-carotene against carcinogenesis: spontaneous liver carcinogenesis and promoting stage of lung and skin carcinogenesis in mice are suppressed more effectively by alpha-carotene than by beta-carotene. AB - Although beta-carotene has been considered to be a key cancer preventive agent in green and yellow vegetables, other types of carotenoids, such as alpha-carotene, may also contribute to anticarcinogenic action, since these carotenoids usually coexist with beta-carotene and are detectable in human blood and tissues. In this study, we compared the inhibitory effect of natural alpha-carotene, obtained from palm oil, with that of beta-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by alpha-carotene supplementation (per os administration in drinking water at a concentration of 0.05%, ad libitum) as compared with that in the control group (P < 0.001, Student's t test). On the other hand, beta-carotene, at the same dose as alpha-carotene, did not show any such significant difference from the control group. Furthermore, we also compared the antitumor-promoting activity of alpha-carotene with that of beta-carotene against two-stage mouse lung carcinogenesis (initiator, 4-nitroquinoline 1-oxide; promoter, glycerol). alpha-Carotene, but not beta-carotene, reduced the number of lung tumors per mouse to about 30% of that in the control group (P < 0.001, Student's t test). The higher potency of the antitumor-promoting action of alpha-carotene compared to beta-carotene was confirmed in other experimental systems; e.g., alpha carotene was also found to have a stronger effect than beta-carotene in suppressing the promoting activity of 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice. These results suggest that not only beta-carotene, but also other types of carotenoids, such as alpha-carotene, may play an important role in cancer prevention. PMID- 1423304 TI - Frequent p53 gene mutations in blast crisis of chronic myelogenous leukemia, especially in myeloid crisis harboring loss of a chromosome 17p. AB - We investigated chromosome alterations and mutations of the p53 gene in 118 samples from 92 patients with chronic myelogenous leukemia in various clinical phases, i.e., chronic phase, accelerated phase, and blast crisis (BC). Single strand conformation polymorphism analysis and subsequent nucleotide sequencing disclosed no alteration of the p53 gene in chronic phase (no mutation in 80 samples), while five of 31 BC samples showed point mutations: four in myeloid and one in lymphoid crisis. One of seven accelerated phase samples also showed a p53 gene mutation. Ten of 31 BC samples showed loss of one of the short arms of chromosome 17 (17p) through the formation of isochromosome 17q, i(17q), or unbalanced translocations. Loss of heterozygosity at the p53 locus in the accelerated phase and BC was detected only in two cases with i(17q) but not in seven cases with normal chromosome 17 homologues, suggesting that loss of one p53 allele is rare without cytogenetically detectable loss of a 17p. Among those six samples with p53 gene mutations, five showed loss of a 17p cytogenetically, and only one lymphoid crisis case exhibited normal chromosome 17 homologues. Thus, mutations of the p53 gene were closely associated with myeloid crisis with loss of a 17p (four mutations in ten samples), in contrast to myeloid crisis with normal chromosome 17 homologues (zero in 13) or lymphoid crisis (one in seven). Our results also suggest that alterations of the p53 gene might occur after loss of a 17p during the course of chronic myelogenous leukemia. PMID- 1423305 TI - Clonal analysis of human breast cancer by means of the polymerase chain reaction. AB - Clonality of human breast cancer was analyzed in small DNA samples prepared from cryostat sections, by means of the polymerase chain reaction (PCR). The method used for clonal analysis was based on restriction fragment length polymorphism of X-chromosome-linked phosphoglycerokinase (PGK) gene and on the differential methylation of the PGK gene due to random inactivation of one of two X chromosomes by methylation in females. All the 20 breast cancer samples analyzed by the PCR-based method were monoclonal in origin and adjacent normal breast tissues were polyclonal. When DNA samples were prepared from widely separated sites of cancers, every sample was found to be monoclonal, always exhibiting inactivation of the same X-chromosome in each tumor. The study on sensitivity showed that the PCR-based method for clonal analysis can detect the presence of monoclonal cells against a polyclonal background when the monoclonal cell population is 50% or more. These results demonstrate that clonal analysis by means of PCR offers a good method for studying the clonality in small DNA samples prepared from cryostat sections of tumors. This method could be applied to distinguish between benign (polyclonal) and malignant (monoclonal) breast lesions. PMID- 1423306 TI - Phase I clinical and pharmacological study of chloroquinoxaline sulfonamide. AB - Chloroquinoxaline sulfonamide (CQS) is a halogenated heterocyclic sulfanilamide identified by the in vitro human tumor colony-forming assay as an active agent in a variety of human solid tumors. In this phase I study, 182 courses of CQS were administered intravenously every 28 days to 88 patients at doses ranging from 18 to 4870 mg/m2. Hypoglycemia associated with hyperinsulinemia was the dose limiting adverse effect at 4870 mg/m2. Supraventricular tachyarrhythmias were observed at doses > 4000 mg/m2. Less common reactions included infusion site phlebitis, nausea, anemia, alopecia, perioral numbness, and diarrhea. Cumulative toxicity was not observed. Minor objective antitumor responses were noted in 7 patients; 6 of the 7 responses occurred in patients with non-small cell lung cancer. Results of pharmacokinetic studies were consistent with the preclinical observations that CQS is highly bound to plasma protein. Plasma elimination followed a two-compartment model; the mean t 1/2 alpha was 2.7 +/- 0.3 h and the t 1/2 beta was 52 +/- 6 h (+/- SE). The total body clearance and the volume of distribution at steady state of CQS both increased with the dose (distribution at steady state, 3.7-10.5 liter/m2; total body clearance, 53-264 ml/h/m2 for doses of 18-4060 mg/m2) and may reflect saturation of the protein binding and "free" drug clearance. Although inactive against common animal tumors in preclinical screening systems both in vitro and in vivo, CQS has demonstrated definite activity in the human tumor stem cell colony-forming assays, as well as modest anticancer activity in this phase I study in patients with advanced solid tumors. The pharmacokinetic results and the limiting effect of transient hypoglycemia suggest that considerably higher cumulative doses of CQS could be administered using a more frequent dosing schedule. PMID- 1423307 TI - Polyethylene-glycol-mediated delivery of liposome-entrapped pigments into fibroblasts: experimental pigment cells as models for mutator phenotypes. AB - The role of epidermal melanin pigments in the development of skin cancer remains unclear. A new technique for the specific introduction of compartmentalized melanin into nonpigmented human fibroblasts through the use of liposomes and polyethylene glycol (PEG) is presented. The delivery of liposome-encapsulated material to cells was characterized by: (a) high efficiency of delivery through PEG-mediated endocytosis at 37 degrees C; (b) intracellular acidification of liposome entrapped pH-sensitive 8-hydroxypyrene-3,6,8-trisulfonic acid after delivery; (c) similar incorporation and acidification of apolipoprotein E associated liposomes into fibroblasts via the low-density lipoprotein-receptor pathway; and (d) discharge into the extracellular space after incorporation. Similar experiments were carried out with melanin-containing liposomes that were used to introduce compartmentalized melanin into fibroblasts, through PEG mediated delivery. These "artificial" melanocytes had functional analogies to genuine melanocytes in that (a) in both cell types melanin compartmentalization was at a lower pH; and (b) liposome contents were later expelled in analogy to the putative biological process of melanin expulsion from the melanocyte. The modified fibroblasts provided potential "mutator" phenotypes with specific melanin pigmentation, and established a new basis for studying the role of melanin pigmentation in cancer development. PMID- 1423308 TI - Deletion of chromosome 11p13-11p15.5 sequences in invasive human ovarian cancer is a subclonal progression factor. AB - In human ovarian cancer, multiple specific chromosomal deletions can be found by cytogenetic analysis or molecular techniques such as restriction fragment length polymorphism probing. This work confirms the loss of HRAS alleles in 1 out of 2 cases of invasive ovarian cancer as determined in 32 samples or cell lines derived from 19 patients. Results with other polymorphic probes indicate that a consensus deletion probably includes 11p15.5-11p13. Tumor suppressor genes might be located in the deleted area, and deletion of the gene might then play a role in disease progression. Examination of DNA from distinct tumor sites of individual patients indicates clonal heterogeneity in the malignant cell population, indicating that loss of 11p sequences is a late event in the disease progression. Loss of alternate 11p alleles at different disease sites in one patient is inconsistent with the current model of tumor suppressor gene inactivation. The 11p deletion seems to be limited to ovarian cancers in younger patients. Eight novel permanent ovarian cancer cell lines, previously not described in the literature and derived from tumor sites from five patients, were included in the current analysis. PMID- 1423309 TI - Reduction of systemic exposure and toxicity of cisplatin by encapsulation in poly lactide-co-glycolide. AB - The tissue distribution and normal tissue toxicity of cisplatin (cDDP) administered as poly-lactide-co-glycolide (PLAGA) microspheres, developed for loco-regional administration of cDDP to the liver, were studied in Wag/Rij rats. Venoportal administration of this formulation resulted in a reduction in total systemic and renal toxicity, which correlated with a decrease in normal tissue exposure to cDDP while maintaining high liver platinum levels. Liver-to-kidney platinum level ratios were 28 times higher after 4 h and 19 times higher after 24 h with PLAGA-cDDP microspheres than with free cDDP. Liver-to-blood platinum ratios at these times were 38 times and 36 times higher using PLAGA-cDDP. In a CC531 colon carcinoma liver micrometastases model, cytotoxicity of microsphere released cDDP was confirmed in vivo by equal inhibition of tumor growth by PLAGA cDDP and free cDDP over a period of 26 days. Free cDDP, however, caused significantly more histological renal damage and total body weight loss. The results were supported by the finding of higher plasma creatinine and urea concentrations 26 days after administration of free cDDP. Kidney platinum levels were 7 times lower when PLAGA-cDDP was used. These findings indicate a sparing effect on normal tissues when cDDP is targeted to the liver by formulation in PLAGA. PLAGA-cDDP microspheres may, therefore, be a useful and effective addition to current techniques of loco-regional chemotherapy for disseminated hepatic tumors. PMID- 1423311 TI - Effect of buthionine sulfoximine and ethacrynic acid on cytotoxic activity of mitomycin C analogues BMY 25282 and BMY 25067. AB - BMY 25282 and BMY 25067, analogues of mitomycin C (MMC), were synthesized in an attempt to increase the therapeutic potential of the parent drug. The present studies were undertaken to determine if the cytotoxicity of MMC or its analogues is affected by cellular glutathione (GSH) and/or GSH transferase (GST) levels by using sensitive (P388/S) and multidrug resistant (P388/R-84) mouse leukemia cells as a model. P388/R-84 cells were cross-resistant to all three drugs. BMY 25067 was > 100 times more cytotoxic than MMC in both the cells. MMC and BMY 25282 produced significantly lower DNA interstrand cross-links (ISC) in P388/R-84 cells, whereas BMY 25067 induced ISC formation was comparable in these cells. GSH depletion with D,L-buthionine-S,R-sulfoximine (BSO) increased sensitivity to MMC, BMY 25282, and BMY 25067 by 3.4-, 4.1-, and 1.8-fold, respectively, in the resistant cells. Pretreatment of P388/R-84 cells with a nontoxic concentration of ethacrynic acid (EA) (10 micrograms/ml for 1 h), an inhibitor of GST activity, also resulted in a significant increase in the cytotoxic activities of MMC and BMY 25282 (3.8- and 3.1-fold, respectively), but not of BMY 25067. Combined pretreatment of P388/R-84 cells with BSO and EA caused further increase in the cytotoxic activities of both MMC and BMY 25282. Potentiation of BMY 25067 cytotoxicity by combined BSO and EA pretreatments was similar to that observed by BSO pretreatment alone. The ISC formation by MMC and BMY 25282 were also increased significantly by BSO or EA pretreatment in these cells. Whereas BSO treatment increased BMY 25067 induced ISC formation, it was not affected by EA pretreatment. These results suggest that (a) a potentiation of the cytotoxic activity of MMC or BMY 25282 can be achieved by GSH depletion and/or GST inhibition, (b) the enhanced cytotoxicity may be caused at least in part by the increased formation of drug-DNA cross-links, and (c) the mechanism of BMY 25067 cytotoxicity may be different from the other two drugs. The results of the present study also suggest that BMY 25067 may be seriously considered for further clinical development because it is much more active than MMC, and unlike the parent drug cytotoxicity of BMY 25067 does not seem to be affected by GST levels, which have been suggested to play an important role in cellular resistance to several cancer chemotherapy drugs. PMID- 1423310 TI - Inhibitory effect of green tea on the growth of established skin papillomas in mice. AB - In 10 separate experiments, mice with established chemically induced or UV light induced skin papillomas were treated continuously with green tea in the drinking water or with i.p. injections of a green tea polyphenol fraction or (-) epigallocatechin gallate three times a week for 4-10 weeks. Partial tumor regression or > 90% inhibition of tumor growth, as measured by changes in tumor volume per mouse, was observed in 5 experiments, and marked inhibition of tumor growth (46-89%) was observed in 5 additional experiments. Treatment of the mice with green tea or green tea constituents had an inhibitory effect on body weight increases in several but not all of the studies. Examination of the data from all ten experiments revealed that complete tumor regression occurred in 14 of 346 papilloma-bearing mice (4%) that were treated with green tea in the drinking water or with i.p. injections of green tea constituents, whereas none of the 220 papilloma-bearing control mice treated with only vehicle exhibited complete tumor regression. These observations indicate that oral administration of green tea, i.p. administration of a green tea polyphenol fraction, or i.p. administration of (-)-epigallocatechin gallate inhibited the growth and/or caused the regression of established experimentally induced skin papillomas. PMID- 1423312 TI - Elevated expression of the ornithine decarboxylase gene in human esophageal cancer. AB - The mechanisms involved in sustaining the high levels of ornithine decarboxylase (ODC) activity in human cancers are not well defined. We examined the level of expression of ODC mRNA together with ODC activity in surgically excised human cancers, including esophagus, stomach, colon, and liver tumors, the objective being to determine whether the ODC mRNA level correlates with enhancement of ODC activity in these cancers. Among these tumors, the esophageal cancers had the highest ODC activity (120 +/- 43.9 pmol of CO2/h/mg of protein), compared with the stomach (37.6 +/- 13.7), colon (22.8 +/- 5.9), and liver (10.2 +/- 5.6) cancers. A remarkable increase in ODC mRNA was seen in all of the esophageal cancers. The ratio of ODC mRNA in the tumors, relative to the paired normal tissues, was 14.6 +/- 3.7. Some increase was noted in some of the stomach (2.9 +/ 0.9) and colon (2.1 +/- 0.9) cancers, but there was no increase in the liver tumors (0.9 +/- 0.2). A significant correlation was noted between ODC activity and mRNA expression in cancerous and noncancerous tissues of the esophagus, stomach, and colon, thereby suggesting that increased steady-state mRNA may be responsible for the high ODC activity in these tumors. Southern blot analysis of the DNA from the esophageal cancers revealed no amplification or significant rearrangement of the gene. Mechanisms sustaining high ODC mRNA levels in esophageal cancers may be an enhancement of the promoter activity of this gene or stabilization of the mRNA. PMID- 1423313 TI - Quercetin arrests human leukemic T-cells in late G1 phase of the cell cycle. AB - The effect of quercetin, a flavonoid found in many plants, on the proliferation of human leukemic T-cells was analyzed. Quercetin reversibly blocked the cell cycle at a point 3-6 h before the start of DNA synthesis. Expression of the growth-related genes histone H4, cyclin A and B, and p34cdc2 was suppressed in cells blocked with quercetin. Comparison of the quercetin arrest points with those of the cell cycle inhibitors aphidicolin and mimosine revealed a temporal order of arrest points in G1 of quercetin, mimosine, and aphidicolin. Mimosine and aphidicolin did not inhibit the expression of cyclin A or p34cdc2, whereas all three reagents inhibited expression of cyclin B. Low concentrations of the protein inhibitor cycloheximide inhibited release of the quercetin but not the mimosine or aphidicolin block. A [35S]methionine-labeled M(r) 60,000 protein disappeared in quercetin-treated cells and was rapidly synthesized after removal of quercetin, suggesting the possibility that the M(r) 60,000 protein induces DNA synthesis after the cell is released from a quercetin block. These results suggest the usefulness of quercetin in studies of the regulation of late G1 phase. PMID- 1423314 TI - Fibroblasts transformed by different ras oncogenes show dissimilar patterns of protease gene expression and regulation. AB - NIH 3T3 cells transformed by different activated ras genes showed different patterns of protease gene expression, indicating the existence of least two pathways for NIH 3T3 transformation from mutated ras genes. In cells transformed by activated mammalian EJ-ras and chimeric EJ/vHa-ras, high constitutive levels of urokinase plasminogen activator (uPA) mRNA and/or phorbol-12-myristate-13 acetate (PMA) inducibility of the uPA mRNA was observed. However, PMA did not induce cathepsin L (CL) mRNA levels in these same cell lines. In contrast, NIH 3T3 cells transformed by homologous yeast RAS1Leu sequences showed low levels of uPA mRNA and a lack of PMA inducibility of uPA mRNA, but did show high constitutive levels of the mRNA for CL and/or PMA inducibility of CL mRNA expression. Based on their differences in PMA inducibility these two phenotypes are designated rasuPA+/CL- and rasCL+/uPA-, respectively. Run-on assays indicated the differences in the levels of CL and uPA mRNA with ras transformation and phorbol ester induction are due to changes in transcription rates. Based on the observation of the two ras-transformed phenotypes for protease expressions, we asked whether uPA and CL can substitute for each other in the promotion of experimental metastasis. Injection of in vitro antisense inhibited cells in nude mice showed an inhibition of lung colonization by anti-uPA only in the rasuPA+/CL phenotype and by anti-CL only in the rasCL+/uPA- phenotype. The data thus show the existence of two distinct activated ras-transformed metastatic phenotypes induced in the same parental cell line and that uPA or CL protease expressions alternatively facilitate the metastasis of cells with one ras phenotype and not with the other. PMID- 1423315 TI - Identification of the eleventh complementation group of UV-sensitive excision repair-defective rodent mutants. AB - The drug-sensitive mutant UVS1, isolated from the Chinese hamster cell line CHO9, was previously found to complement the UV sensitivity of the excision repair defective rodent mutants representative of groups 1 to 8 (Hata et al., Cancer Res., 51: 195-198, 1991; M. Numata et al., personal communication). Recently two new complementation groups of UV-sensitive CHO mutants, e.g., groups 9 and 10, have been identified (Stefanini et al., Cancer Res., 51: 3965-3971, 1991). In this paper we demonstrate that the repair defect in UVS1 cells is genetically different from those present in the mutants CHO7PV and CHO4PV, representing groups 9 and 10, respectively. Therefore, UVS1 represents a new complementation group of UV-sensitive rodent cell lines, the eleventh group. PMID- 1423316 TI - Frequent somatic mutations of the APC gene in human pancreatic cancer. AB - The APC (adenomatous polyposis coli) gene is responsible for familial adenomatous polyposis and is also associated with the development of sporadic tumors of the colon and stomach. To investigate whether or not mutations of APC play any role in tumors arising in other organs, we examined somatic mutations of this gene in sporadic (nonfamilial) renal cell carcinomas, hepatocellular carcinomas, and cancers of the lung and pancreas. DNAs isolated from tumors were examined by means of a RNase protection analysis, coupled with the polymerase chain reaction followed by DNA sequencing of the polymerase chain reaction products. By screening a part of the APC coding region, we detected somatic mutations in four of ten pancreatic cancers; each of these mutations would yield a truncated APC product due to a 1- or 5-base pair deletion. These results imply that mutations in APC contribute to carcinogenesis in the pancreas. PMID- 1423317 TI - Urinary excretion of O6-butylguanine after the administration of N-nitroso-N butylurea in rats. AB - O6-Butylguanine was detected in the urine of rats given the butylating agent N nitroso-N-butylurea. O6-Butylguanine contents in the 24-h rat urine samples after i.p. doses of 50, 100, and 200 mg/kg N-nitroso-N-butylurea were 1.03 +/- 0.41 (SE), 8.30 +/- 1.70, and 59.53 +/- 6.52 pmol, respectively. This suggests that O6 butylguanine formation in nucleic acids might be repaired in vivo, possibly by base excision, besides other mechanisms. After i.v. doses of 0.1 and 1 mg/kg of O6-butylguanine to rats urinary excretion did not exceed 2% of the administered dose, suggesting that the amount of O6-butylguanine effectively released by base excision might be much larger than that detected in the urine after N-nitroso-N butylurea. Inhibition of the enzyme O6-alkyl-DNA transferase by N nitrosodimethylamine increased urinary O6-butylguanine resulting from exposure to N-nitroso-N-butylurea (100 mg/kg i.p.) up to four times, thus confirming an alternative DNA repair mechanism. PMID- 1423318 TI - Analysis of a metastasizing testicular mixed gonadal stromal tumor with osteosarcoma components suggests that a malignant tumor with the histology of osteosarcoma may develop without primary involvement of RB1 and TP53. AB - A malignant stromal tumor of the testis with an osteosarcoma component and five of its metastases mainly containing osteosarcoma have been analyzed for RB1 and TP53 abnormalities. Whereas in the primary tumor and in some of the metastases loss of heterozygosity could not be detected for RB1 or for the 17p13 region in which TP53 is located, other metastases showed such losses of heterozygosity. By polymerase chain reaction analysis an 18-base pair deletion from exon 5 of the TP53 gene was found in a small proportion of primary tumor cells and in one of the metastases, but not in the other metastases. Therefore, in this case neither RB1 nor TP53 seems to play an essential role in the initiation of osteosarcoma. PMID- 1423319 TI - Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk. AB - Cytochrome P450IIE1 is responsible for the activation of carcinogenic N nitrosamines, benzene, urethane, and other low-molecular-weight compounds. Restriction fragment length polymorphisms (PstI and RsaI restriction enzymes) have been identified in the cytochrome P450IIE1 transcription regulatory region that may affect expression. This study describes the PstI and RsaI polymorphisms in different racial populations and in a case-control study of lung cancer. The allelic frequencies were markedly different in Japanese, African-Americans, and Caucasians: the PstI rare allele was present at a frequency of 2% in Caucasians, 5% in African-Americans, and 24% in Japanese (P < 0.05). For the RsaI rare allele, frequencies were 2% in Caucasians, 2% in African-Americans, and 27% in Japanese (P < 0.05). The assay was also applied to 128 individuals enrolled in a case-control study of lung cancer. Although limited in statistical power, the data indicate no evidence for an association in the aggregate of cytochrome P450IIE1 PstI [for which the odds ratio was 0.7 (95% confidence interval (C.I.) = 0.2-2.8)] or RsaI [for which the odds ratio was 0.9 (95% C.I. = 0.2-5.4)] restriction fragment length polymorphisms with lung cancer in this U.S. population. When analyzed by race, the lung cancer odds ratio for the PstI mutant allele in African-Americans was 0.19 (95% C.I. = 0.03-1.38), and in Caucasians it was 4.13 (95% C.I. = 0.34-48.8). For the RsaI mutant allele, the odds ratios were 0.20 (95% C.I. = 0.02-2.43) and 4.28 (95% C.I. = 0.35-50.6), respectively. The ethnic differences of these restriction fragment length polymorphisms might be related to genetic susceptibilities for lung cancer among Caucasians and for gastric or esophageal cancer among Japanese. PMID- 1423320 TI - The role of surface HLA-A,B,C molecules in tumour immunity. AB - It is well established that MHC class I molecules present peptides from endogenous proteins, such as virus or tumour antigens, to CD8+ T lymphocytes. This implies that expression of MHC class I molecules on tumours is also mandatory for an effective T cell response against neoplasias. Indeed, numerous murine models exist (such as IC9, 3LL, P815) in which the existence of MHC presented tumour antigens and a protective CTL response have been well documented (reviewed in Hammerling et al, 1987). However, the key question of whether cytolytic T cell attack has a role in human cancer remains unsolved. Similarly, the role of NK cells is unclear; these seem to lyse cells with low levels of MHC class I expression more efficiently. So far, human tumour specific antigens that can be presented by HLA molecules have not been identified on the molecular level. For a subpopulation of patients with malignant melanoma, the existence of tumour antigen can be deduced from the existence of tumour specific cytotoxic T cells isolated from TIL. However, for other epidemiologically more important tumours such as carcinomas of the colon, breast and lung, even indirect evidence is still missing. It is thus unknown how many tumours express tumour specific antigen at all and whether these putative antigens are of unique specificity or are shared by certain groups of (histologically related) neoplasias. Most reports agree that malignant cells in general have a more or less pronounced propensity to express class I molecules abnormally and often in the sense of hypoexpression or (sublocus selective) loss. Mechanisms inducing aberrant expression are numerous. Immunohistochemical studies revealed that an abnormal content in surface class I/beta 2m may be associated with other aspects of dedifferentiation of the tumour and hence may eventually correlate with biological signs of an increased grade of malignancy. Consequences of defective MHC class I expression for the survival of a malignant clone may theoretically consist of an escape from cytotoxic T cell attack or in an increased susceptibility for NK mediated lysis. In view of the fact that a particular antigen in a cell will be presented only by one or few HLA alleles on the cell, one would not expect that immunoselection would lead to a loss of all HLA alleles. It can be deduced from the few existing clinical studies on the prognostic impact of aberrant MHC class I expression that immunoselection by one way or the other is not a relevant mechanism in terms of tumour biology.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423321 TI - Immunity and metastasis: in situ activation of protective T cells by virus modified cancer vaccines. AB - Data from animal models and clinical observations from immunotherapy trials suggest that tumour reactive host T cells can have an important role in the control of metastasis and tumour rejection. If tumour cells express tumour associated antigens recognizable by T cells, their antigenicity/immunogenicity is usually weak, and accessory molecules are required to stabilize the T cell/tumour cell interaction and to deliver the antigen/T cell receptor (TCR) mediated signal (signal 1) together with costimulatory signals (signal 2). The sum of these intracellular signals received by the corresponding T cells with the fitting TCR may determine the intensity of the anti-tumour response. A deficiency of anti tumour T cell responsiveness in cancer patients could thus be due to a lack of signal 1 and/or signal 2 or to inappropriate timing between the two signals. A further point to consider is the distinction between primary and secondary T cell responses: between priming of virgin T cells and activation of primed memory T cells. Our experience with a metastasizing animal tumour suggests that the microenvironmental requirements for these two steps differ. This means that the site of a primary (or secondary) tumour may be good for one type of response (eg priming) but not for the other (eg memory response). One purpose of active immunotherapy could therefore consist of exposing the cancer patient's immune system to its own tumour cells in the context of a new microenvironment that may be well suited for activating memory type responses. On the basis of these considerations, we discuss the possibilities of immunological intervention and propose the use of a two-component cancer vaccine for active immunization and two signal stimulation of endogenous memory T cells in tumour bearing animals or cancer patients. As a specific component, we favour the use of intact, viable, radiation inactivated autologous tumour cells, which should represent the closest match to the patient's own cancer. If this is not possible, cells from allogeneic corresponding tumours or tumour cell lines could be used. On a longer time scale of treatment, one may consider an induction therapy with autologous vaccine followed by maintenance therapy (when autologous material has run out) with allogeneic material. As a second non-specific component, we favour and have good experience with a virus, NDV, which can easily attach to the cells of the vaccine and facilitate the delivery of costimulatory signals to tumour reactive T cells following postoperative vaccination of tumour bearing hosts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423322 TI - MHC loss in colorectal tumours: evidence for immunoselection? AB - The reason for MHC loss in colorectal tumours remains uncertain. Strong evidence that the downregulation is due to immunoselective pressure would be provided by the finding of deletions or mutations directly involving MHC heavy chain or beta 2m genes. However, although in contrast to studies on cell lines (Brodsky et al, 1979a; Travers et al, 1986; D'Urso et al, 1991), our findings are in agreement with other evidence (Doyle et al, 1985; Blanchet et al, 1990; Henseling et al, 1990) that the most common mechanism of downregulation is regulatory, mostly at a transcriptional level. Does this imply that MHC loss in tumours can be incidental? The answer to this question will depend on the nature of the initial lesion identified. The existence of cis-acting regulatory mechanisms and dominant negative trans-acting mechanisms suggests that a single mutational event could result in transcriptional changes affecting a number of genes. Thus, selective pressure could result in tumour variants whose loss of MHC is due to transcriptional regulatory changes. As these mechanisms are unravelled, it may be possible to draw conclusions about the aetiology of MHC loss in colorectal tumours. Meanwhile, in the absence of demonstrated CTL to colorectal tumours, the case for immunoselective pressure remains unproven. PMID- 1423323 TI - T cell immune response to cancer in humans and its relevance for immunodiagnosis and therapy. AB - Review of the relationship between the degree of immunosuppression and malignancy in patients on immunosuppressive drugs or immunosuppressed by HIV infection, postoperative blood transfusion or pregnancy provides the most convincing evidence of the importance of intact T cell immunity in resistance to cancer. Defective HLA class I and II antigen expression on tumours arising in non immunosuppressed individuals and correlation of these changes with increased malignancy and diminished TIL provide the most convincing evidence that one factor necessary to ensure survival of most spontaneous tumours is mutation that enables tumour cells to escape rejection by cytotoxic T cells. These changes are less frequent in tumours in immunosuppressed patients, and preliminary data suggest that use of cytokine therapy is more successful in these tumours and the one in five spontaneous tumours demonstrating normal expression of HLA antigens and high levels of T cell infiltration. These observations suggest that future use of this therapy should be focused on these cases. All modalities of cancer therapy except hormone therapy (ie surgery, radiotherapy and chemotherapy) suppress immune responses. Defects of HLA antigen expression are less marked in early cancer. Combinations of immunotherapy with conventional treatment at presentation, including hormone therapy in view of data demonstrating regeneration of the thymus after castration, needs further investigation. Preliminary results from randomized trials involving nearly 300 individuals accidentally exposed to carcinogens demonstrated nearly 60% reduction of incidence of malignancy at 5 years in the arm receiving non-specific immunotherapy. If confirmed, such an approach might be more cost-effective as an approach for cancer prevention than organ specific cancer screening or vaccination against cancer associated viruses such as hepatitis B or papillomaviruses. PMID- 1423324 TI - Identification of tumour rejection antigens recognized by T lymphocytes. AB - On the basis of the results reviewed here, there are two major mechanisms whereby tumour rejection antigens may arise. The first mechanism is mutational. Point mutations occurring in a large variety of genes may produce new antigenic peptides, either by providing them with the ability to bind to MHC class I molecules or by providing them with a new epitope (Fig. 2). The second mechanism is the activation of a gene that is silent in normal tissues and for which no strong natural tolerance has been established. Plausible candidates for the mutational mechanism are the "tumour specific transplantation antigens" observed on methylcholanthrene induced tumours and tumours induced by ultraviolet light. The diversity of these antigens appears to be very large, like that of the tum- antigens. Moreover, these tumours have been obtained with high doses of carcinogens, which are proven mutagens. On the other hand, a P815 tumour rejection antigen appears to arise through the activation of a silent gene, and it may turn out that this is the rule for most tumour rejection antigens. It is our hope that other genes coding for mouse and human tumour rejection antigens will soon be identified, so that it will become clear whether the activational mechanism is the rule or the exception. In our view, this is a crucial issue. Insofar as tumour rejection antigens result from mutations, they may be highly specific for every individual tumour. The tumour specific nature of these antigens would then be easily ascertained. However, active immunization of cancer patients would require that a tumour cell line be obtained from each patient, a most unpractical prospect. If, on the other hand, production of tumour rejection antigens results from the activation of a normal gene, then there is a good probability that the same gene may be activated in many different tumours, being perhaps preferentially shared by tumours of the same histological type. This would probably not result in the expression of the same antigen in all these tumours, because the patients would differ in their presenting molecules, which are determined by their HLA haplotype. However, a subset of the tumours expressing the same "tumour rejection" gene should share the same class I restricting element, so that all of these patients could be immunized with a cell that would express the gene and carry the appropriate HLA molecule.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423325 TI - T cell responses to human malignant tumours. AB - The immunological and molecular mechanisms that govern T cell responses to human malignant tumours are just starting to be understood within a more complex framework of humoral, cellular and molecular interactions. The definition of multiple antigens simultaneously expressed on human melanoma, as detected with cytolytic T cells in immunoselection experiments, is a first step towards the molecular characterization of these antigens. Observations on the influence of expression of restriction elements of the major histocompatibility complex on the recognition of these tumour associated antigens have advanced our understanding of how the immune system responds to cancer cells in vivo. It is specificity that is tuning the immune system, not only in cancer. The molecular characterization of the first human cancer antigen recognized by CTL is now under way as outlined by Boon et al in this issue. PMID- 1423326 TI - Lessons from T cell responses to virus induced tumours for cancer eradication in general. AB - Immunotherapy of virus induced tumours by adoptive transfer of virus specific cytotoxic T cells (CTL) is now feasible in experimental murine systems. These CTL recognize viral peptide sequences of defined length presented in the groove of MHC class I molecules. Effective eradication of large tumour masses requires coadministration of IL-2. In essence, T cell immunity against virus induced tumours does not differ from anti-viral T cell immunity in general. Tumour escape strategies are numerous but, in various instances, can be counteracted by defined measures. Initiation of CTL responses against poorly immunogenic non-virus induced tumours (the majority of human cancer) requires novel strategies to overcome T cell inertia. Rather than waiting to see whether tumour specific CTL (against unknown antigens) can be cultured from TIL, we propose an alternative strategy in which CTL are raised against target molecules of choice, including differentiation antigens of restricted tissue distribution (autoantigens) or mutated/overexpressed oncogene products. The various steps proposed include: (a) identification of target molecules of choice; (b) identification in these target molecules of MHC allele specific peptide motifs involved in peptide binding to MHC molecules; (c) evaluation of actual binding of such peptides to specific MHC class I molecules; (d) in vitro CTL response induction by such peptides, presented either by highly efficient antigen presenting cells (such as processing defective cells, which carry empty MHC class I molecules) loaded with a single peptide or by dendritic cells, both cell types being capable of primary CTL response induction in vitro and (e) adoptive transfer of tumour specific CTL generated in vivo or, more conveniently, vaccination with immunodominant peptides. The latter possibility seems to be feasible because peptide vaccination with a single immunodominant viral peptide can install CTL memory and confer protection against lethal virus infection. PMID- 1423327 TI - The importance of steroid hormones in prostate cancer. AB - Steroid hormones have an important role in prostate biology. Androgens are crucial for the normal development of the prostate gland and in maintaining its functional state in the adult. It seems that the prolonged presence of androgens might also be an important factor in the development of prostate cancer. In addition, androgens and oestrogens appear to play some part in the development of benign prostatic hyperplasia, although the exact nature of their role has not been clearly defined. Stimulation of prostate cancer growth by androgens is well established, with androgen withdrawal therapy constituting the most effective therapy in men with prostate cancer. Additive steroid therapy of metastatic prostate cancer with oestrogens or progestins has also proven effective. The effects of androgens on prostate cancer cell growth might be mediated through modulation of growth factor expression and alteration of growth factor receptor levels. Androgen response can be modulated by the expression of mutated oncogenes such as ras. Androgen independence can occur through a loss of AR expression or mutation of the AR; however, the patterns of AR expression in normal prostatic tissue from development to adulthood and in cancer are now just beginning to be described. Other steroids, such as the retinoids, show promise as preventive agents, possibly through the modulation of growth factors. PMID- 1423328 TI - The importance of normal and abnormal oestrogen receptor in breast cancer. AB - We have used the screening techniques of CMC and SSCP of selected PCR fragments, and also gel retardation assays, to discover a number of ER variants in clinical breast cancer tissues. We have found base pair insertions, transitions, and deletions, and deletions of exons 3, 5 and 7. Using a yeast transactivation assay, we have discovered receptors with outlaw function consisting of both dominant positive receptors that were transcriptionally active in the absence of oestrogen and dominant negative receptors that were transcriptionally inactive themselves but prevented normal ER function. Future efforts should focus in particular on such dominant positive and dominant negative variants. With regard to positive variants, we should like to know whether they stimulate tumour growth and, if so, whether they can be turned off. With regard to dominant negative variants, we should like to determine whether they can inhibit tumour growth and, if so, whether they can be turned on. PMID- 1423329 TI - Cellular heterogeneity and mutant oestrogen receptors in hormone resistant breast cancer. AB - In summary, we propose that the molecular heterogeneity of ER in breast tumour cells, characterized by the presence of mutant receptor forms, generates the cellular heterogeneity evident when PR or DNA ploidy are analysed in cell subpopulations. Furthermore, it is likely that cellular heterogeneity leads to the lack of uniformity in response to tamoxifen that we have described. We find that heterogeneity of PR and DNA ploidy reflects the existence of mixed subpopulations of breast cancer cells that are substantially remodelled under the influence of tamoxifen. It appears likely that different subsets of cells, rather than being "resistant", can be inhibited or stimulated by tamoxifen and that their suppression or outgrowth alters the phenotype of the tumour. PR heterogeneity in solid tumours of patients may predict a mixed, and potentially dangerous, response to anti-oestrogen treatment. As we learn more about the heterogeneity of PR, ER and other proteins in tumours, we may be able to recognize such lethal subpopulations, which the flow cytometry immunoassay can simply and rapidly measure. Our data also suggest that the use of tamoxifen as a chemopreventant in women at high risk of developing breast cancer (Kiang, 1991) should be viewed with caution. PMID- 1423330 TI - Immunolocalization of steroid hormone receptors in normal and tumour cells: mechanisms of their cellular traffic. AB - Experimental conditions are described for the detection of steroid receptors in tissue sections or cells at the light microscope level. Current knowledge about the ultrastructural distribution of these receptors is summarized; the mechanisms of their nuclear localization are described. Karyophilic signals involved in nuclear translocation are characterized by means of in vitro mutagenesis of steroid receptor cDNAs. Studies analysing the subcellular distribution of various transfected receptor mutants in energy depleted cells together with fusion experiments provide evidence for nucleoplasmic shuttling of progesterone receptors. We conclude that the "nuclear" location of the wild type progesterone receptor reflects a dynamic equilibrium between active nuclear import and outward diffusion. We also describe the use of immunocytochemistry in pathology, especially for the detection of steroid receptors in hormone dependent tumours. PMID- 1423331 TI - A molecular strategy to control tamoxifen resistant breast cancer. AB - Our research goal is to develop possible strategies that could have therapeutic implications for the control of breast cancer. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for the majority, who have ER negative disease. There is also both laboratory and clinical evidence to support the position that initially responsive tumours will eventually develop resistance to tamoxifen therapy. Since the ER mechanism is the key to the successful control of tumour growth with anti-oestrogens, we have taken the strategic step of determining whether the ER will reassert growth control in breast tumour cells. We have demonstrated that this is feasible, and it might now be appropriate to plan a "gene therapy" approach to cancer control that is based on reactivation of the ER or the development of a targeted vector. Since the concept of growth control in refractory breast cancer has become a reality, there can now be enthusiasm about developing a means to achieve this therapeutic goal. Indeed, the implications for cancer therapy could be enormous. There is every reason to suppose that other types of cancer cells transfected with steroid receptor genes will respond with growth suppression to the appropriate ligand. We have further broadened our studies of anti-oestrogens to describe a laboratory model to dissect the molecular pharmacology of hormone and anti-hormone action. In practical terms, the model has provided an insight into tamoxifen stimulated growth as a mechanism of tamoxifen resistance. The pharmacology of a model compound, fixed ring 4-hydroxytamoxifen, was changed by a mutant ER. It is possible to envisage the clonal selection of cells with mutated ER or ERE that will thrive on the partial agonist actions of tamoxifen. These cells would, as is observed in the MCF-7 TAM and EnCa101 laboratory models, also respond to oestradiol stimulation. Future studies of mutant receptors in the laboratory and clinic might provide support for a novel mechanism of tamoxifen resistance. What is most encouraging, though, is the finding that the pharmacology of new pure anti-oestrogens is not affected by the mutation in the ER and that the pure anti-oestrogens can control tamoxifen stimulated growth. These observations provide additional support for the development of pure anti oestrogens as a therapy for breast cancer. A clinically acceptable compound could be used as a therapy after tamoxifen failure or perhaps the compound may prevent the development of receptor mutants if it is used as a first line therapy. PMID- 1423332 TI - Steroid antagonists as nuclear receptor blockers. AB - Molecular analysis of sex steroid receptors, together with the availability of a range of ligands for these receptors that affect differentially the physiological actions of the ligand-receptor complex in the cell nucleus, is providing new insights into the processes that control transcriptional activation leading to cell growth. These studies serve to focus attention on the importance of other cell specific factors that are important in determining the transcriptional efficiency of the hormone-receptor complex. Elucidation of the nature and role of such factors may lead ultimately to hormonal or anti-hormonal agents targeted to modulate selected hormone mediated events in specific cells or organs. The sex steroid receptors are prototypes of a much larger family of proteins that control transcription, including proteins that bind to ligands known to be important physiologically, such as thyroid hormones and retinoids, as well as "orphan" receptors for which no ligands have been described. The established value of steroid antagonists in cancer therapy suggests that further developments in the understanding of new members of the steroid receptor superfamily may lead to the development of novel anti-cancer agents. The developing understanding of "cross talk" between steroid-receptor and growth factor-receptor mediated tumour growth stimulatory pathways may also provide previously unrecognized opportunities for tumour therapy. PMID- 1423333 TI - Perspectives on oestrogen receptor function: past and future. PMID- 1423334 TI - Androgen receptor mutants that affect normal growth and development. AB - The elucidation of the molecular structure of the human androgen receptor has facilitated the study of molecular defects associated with androgen insensitivity. In this overview, data are presented on the functional domain structure of the wild type human androgen receptor and on the molecular structure of the androgen receptor from different subjects with the complete form of androgen insensitivity. Mutational domain analysis of the human androgen receptor has revealed that a large carboxyterminal region constitutes the hormone binding domain and that DNA binding is associated with a central basic domain. In addition, separate domains that control trans-activation and nuclear translocation have been identified. Reports on androgen receptor gene structure in individuals with the complete and incomplete forms of androgen insensitivity indicate that gross deletions within the androgen receptor gene are uncommon. The locations of the different point mutations reported cannot be assigned to a single site but are spread throughout the ligand binding and DNA binding domains. A point mutation found in the ligand binding domain of the human androgen receptor in a prostate tumour cell line is the cause of the altered steroid binding specificity observed for the androgen receptor in these prostate tumour cells. A considerable variation in the length of one of the polyglutamine repeats has been reported in the aminoterminal transcription regulating domain of the wild type androgen receptor. Doubling of the length of this particular polyglutamine stretch is correlated with a progressive spinal/bulbar muscular atrophy in a small group of middle aged men. PMID- 1423335 TI - Clinical, immunopathologic, and therapeutic considerations of inflammatory myopathies. AB - The inflammatory myopathies encompass a group of heterogenous muscle diseases which have in common an acquired myopathy with histological signs of endomysial inflammation. We present evidence based on recently emerged clinical, histologic, immunopathologic, demographic and therapeutic observations that these myopathies comprise three major and distinct groups: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM). Immune-mediated mechanisms characteristic for each group appear to play a primary role in the pathogenesis of these diseases. In DM there is an intramuscular microangiopathy mediated by the C5b-9 membranolytic attack complex, leading sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis and perifascicular atrophy. In contrast, in PM and IBM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize MHC-I restricted muscle antigens, leading to phagocytosis and fiber necrosis. Among the viruses implicated in the cause of inflammatory myopathies, only the retroviruses, HIV, HTLV-1 and simian retroviruses, have been convincingly associated with PM. Retroviruses, therefore, appear to be the leading group of viruses capable of triggering these diseases. The treatment of inflammatory myopathies has been largely empirical. A detailed therapeutic plan based on our experience with a large number of patients is presented. Patients with bona fide PM or DM respond to steroids to some degree and for some period of time. In contrast, patients with IBM do not respond to any therapy and the disease should be suspected when a patient with presumed PM has failed treatment. Methotrexate and cyclophosphamide are disappointing. Cyclosporine and Azathioprine are commonly used but they are of uncertain benefit. Plasmapheresis is ineffective. High-dose intravenous immunoglobulin is a promising new therapeutic modality. PMID- 1423336 TI - Pharmacodynamics of the hypotensive effect of levodopa in parkinsonian patients. AB - Blood pressure effects of i.v. levodopa were examined in parkinsonian patients with stable and fluctuating responses to levodopa. The magnitude of the hypotensive effect of levodopa was concentration dependent and was fit to an Emax model in fluctuating responders. Stable responders demonstrated a small hypotensive response. Baseline blood pressures were higher in fluctuating patients; a higher baseline blood pressure correlated with greater hypotensive effects. Antiparkinsonian effects of levodopa temporally correlated with blood pressure changes. Phenylalanine, a large neutral amino acid (LNAA) competing with levodopa for transport across the blood-brain barrier, reduced the hypotensive and antiparkinsonian effects of levodopa. We conclude that levodopa has a central hypotensive action that parallels the motor effects in fluctuating patients. The hypotensive effect appears to be related to the higher baseline blood pressure we observed in fluctuating patients relative to stable patients. PMID- 1423337 TI - Elevated plasma immunoreactive beta-endorphin in anorexia nervosa. AB - Basal morning plasma levels of immunoreactive-beta-endorphin (ir-beta-EP), and 17 beta estradiol (E2) were assessed in 25 adolescents with anorexia nervosa (AN) in comparison to 24 healthy controls. All subjects were drug free for at least 6 weeks. The mean plasma level of ir-beta-EP was significantly higher (84%) in the AN patients when compared with the control subjects. The elevated plasma ir-beta EP may be relevant to the suppression of appetite, tolerance of fasting, and to the hypothalamic hypogonadism in AN. PMID- 1423338 TI - Acetazolamide improves action myoclonus in Ramsay Hunt syndrome. AB - The myoclonus of two patients with Ramsay Hunt syndrome was only partially controlled under treatment with clonazepam, sodium valproate, primidone, and piracetam. Acetazolamide (200 mg daily) was added to these drugs, resulting in a dramatic improvement. Placebo substitution (one patient) and withdrawal of acetazolamide in the other patient resulted in marked aggravation of the myoclonus. The mechanism of action of acetazolamide in myoclonus is unknown. Acetazolamide may be an additional therapeutic possibility for patients with severe action myoclonus. PMID- 1423340 TI - Naloxone or haloperidol but not yohimbine reverse apomorphine-induced respiratory depression. AB - Intravenous injection of low doses of naloxone was found to reverse the respiratory depression induced by apomorphine in chloralose-anesthesized dogs. Similar results were obtained with haloperidol, whereas yohimbine remained ineffective. These data suggest that apomorphine depresses respiratory rate through a mechanism involving both dopamine and opiate mechanisms but not alpha 2 adrenoceptors. Respiratory arrest induced by overdosages of apomorphine can be treated with naloxone. PMID- 1423339 TI - Amnestic syndrome associated with propranolol toxicity: a case report. AB - An elderly woman developed an Alzheimer-like subacute dementia as a result of propranolol toxicity. Analysis of the manifestations showed that severe impairment of memory accounted for virtually all of the abnormalities. There is evidence that cerebral reactions to drug toxicity can exhibit patterns that suggest highly selective involvement of functional subdivisions of the brain. PMID- 1423341 TI - Stereospecific 1,2-cis-glycosylation: a modified thiocyanate method. PMID- 1423342 TI - Conformational analysis of levanbiose by molecular mechanics. AB - A relaxed conformational energy map for levanbiose, O-beta-D-fructofuranosyl-(2-- -6)-beta-D-fructofuranoside, was computed with the molecular mechanics program MM2(87). All torsion angles of the three linkage bonds were driven by 30 degrees increments while two primary alcohol groups were held at three staggered forms. The steric energy of all other parameters was optimized. The side groups were retained at the same relative positions on the two rings in this first part of the study so our results are directly applicable to the study of polymeric levan with identical repeating units. The low-energy dimers did not lead to viable polymers. The interresidue linkage torsion angles defined by C-6-O-2'-C-2'-C-1' (phi) and O-5-C-5-C-6-O-2' (omega) have minima at +60 degrees and -60 degrees, respectively, with accessible minima at other staggered forms. As observed in inulobiose, the preferred torsion angle at central linkage bond defined by C-5-C 6-O-2'-C-2' (psi) was antiperiplanar. An analysis of all conformations of staggered side groups showed that the C-1 and C-1' groups had little effect but the C-6' group showed a preference for chi-6'(O-5'-C-5'-C-6'-O-6') = -60 degrees. The fructofuranose rings were started at the low-energy 4(3)T conformation (angle of pseudorotation, phi 2 = 265 degrees) that was retained except when the linkage conformations created severe inter-residue conflict. PMID- 1423343 TI - Synthesis of a phenyl beta-avobioside derivative of the disaccharide component of avoparcins. AB - The synthesis of the phenyl beta-glycoside of avobiose, a disaccharide fragment present in the antibiotic avoparcin, is reported. It is based on glycosylation of phenyl 3,4,6-tri-O-benzyl-beta-D-glucopyranoside with 2,3,6-trideoxy-4-O-p nitrobenzoyl-3-trifluoroacetamido-L-ribo-hex- 1-enitol, a fully protected glycal of L-ristosamine, in the presence of trimethylsilyl triflate. PMID- 1423344 TI - The reaction of some dicarbonyl sugars with aminoguanidine. AB - The reactions of aminoguanidine (guanylhydrazine) with 3-deoxy-D-erythro-hexos-2 ulose (1a), 3-deoxy-D-glycero-pentose-2-ulose (1b), D-erythro-hexos-2-ulose (1c), and D-glycero-pentose-2-ulose (1d) were examined at 37 degrees at a solution pH of 7.0 (phosphate buffer). For 1a and 1b, two major products were observed and shown respectively to be the 5- and 6-substituted 3-amino-1,2,4-triazine derivatives. The ratios of the products were independent of the amount of aminoguanidine present or the order of mixing the reagents prior to the experiments. For 1c and 1d, only the 5-substituted triazine derivatives were formed. No evidence for hydrazone or bishydrazone formation was observed. PMID- 1423345 TI - Immunochemical characterization of polyclonal and monoclonal Streptococcus group A antibodies by chemically defined glycoconjugates and synthetic oligosaccharides. AB - Synthetic oligosaccharides of increasing complexity that represent different epitopes of the Streptococcus Group A cell-wall polysaccharide were used as haptens and glycoconjugates of bovine serum albumin (BSA) and horse hemoglobin (HHb) to characterize polyclonal and monoclonal antibodies. Rabbits were immunized with the BSA glycoconjugates of a linear trisaccharide, branched trisaccharide, and branched pentasaccharide. The binding specificities of the polyclonal antisera were determined by a series of inhibition ELISA studies in which disaccharide through pentasaccharide haptens were used as inhibitors of antibody-glycoconjugate binding. Monoclonal antibodies derived from mice immunized with a killed bacterial vaccine were selected for their binding to native polysaccharide antigen coupled to BSA and the BSA glycoconjugates of the di- and linear tri-saccharides. Polyclonal antibodies were moderately specific for the oligosaccharide epitope of the immunizing glycoconjugate and only those antibodies raised to the branched pentasaccharide antigen showed cross-reaction with the bacterial antigen. The behaviour of selected monoclonal antibodies parallels the binding profile of polyclonal antibodies in that the two highest titre antibodies were directed toward an epitope displayed by the branched pentasaccharide. PMID- 1423347 TI - Rearrangement of unsaturated 2,4-O-benzylidenehexitol derivatives into C glycosylbenzene derivatives. AB - Acetolysis of (Z)-1,3-di-O-acetyl-2,4-O-benzylidene-6-C-(2,4-dichlorophenyl)-D xylo-he x- 5-enitol (3) afforded (E)-1,2,3,4-tetra-O-acetyl-6-C-(2,4 dichlorophenyl)-D-xylo-hex-5-enit ol and 2-C-[(R)-acetoxy(2,4 dichlorophenyl)methyl]-3,4,6-tri-O-acetyl-2-deoxy- beta-L-galacto- and -beta-L gulo-hexopyranosylbenzene. The mechanism of this new rearrangement was studied by exchanging the substituents at C-1 and C-3 in 3 and those of the aromatic ring attached to C-6. PMID- 1423346 TI - Formation of oligosaccharides from lactitol by Aspergillus oryzae beta-D galactosidase. AB - Six oligosaccharides were first formed from lactitol by a transgalactosylation reaction catalyzed by Aspergillus oryzae beta-D-galactosidase. From the results of methylation analysis, MS, and 1H- and 13C-NMR studies, it was concluded that these oligosaccharides are O-beta-D-galactopyranosyl-(1----4)-O-beta-D galactopyranosyl-(1----4)-D- glucitol, O-beta-D-galactopyranosyl-(1----3)-O-beta D-galactopyranosyl-(1----4)-D- glucitol, O-beta-D-galactopyranosyl-(1----4)-[O beta-D-galactopyranosyl-(1----6)]- D- glucitol, O-beta-D-galactopyranosyl-(1--- 6)-O-beta-D-galactopyranosyl-(1---4)- glucitol, O-beta-D-galactopyranosyl-(1--- 4)-[O-beta-D-galactopyranosyl- (1----5)]-D-glucitol, and O-beta-D galactopyranosyl-(1----4)-[O-beta-D-galactopyranosyl-(1----1)]- D-glucitol. The last three are newly observed oligosaccharides. PMID- 1423348 TI - Synthesis of 2-amino-1,2-dideoxy-D-galactitol hydrochloride and 5-amino-1,4 anhydro-5,6-dideoxy-L-galactitol hydrochloride. PMID- 1423349 TI - The synthesis and characterisation of 2-O-(6-O-L-glycero-alpha,beta-D-manno heptopyranosyl-alpha-D-glucopyran osyl)-alpha,beta-D-glucopyranose. AB - The title compounds were synthesised, and appropriate derivatives were characterised by GLC, GLC-MS, and NMR spectroscopy. The GLC and GLC-MS data proved 2-O-(6-O-L-glycero-alpha-D-manno-heptopyranosyl-alpha-D-glucopyranosyl)- D glucopyranose to be a constituent of the outer-core region of the lipopolysaccharide from Escherichia coli K-12, indicating the heptosyl residue to be linked to the terminal glucopyranose residue. PMID- 1423350 TI - Glucosylenamines as glycosyl acceptors: synthesis of gentiobiosylenamines. AB - The preparation of 2,3,4-tri-O-benzyl- (3), 2,3,4-tri-O-acetyl- (4), and 2,3,4 tri-O-benzoyl-N-(2,2-diethoxycarbonylvinyl)-6-O-trityl-beta- D glucopyranosylamine (5) is described. The reaction of 3-5 with 2,3,4,6-tetra-O acetyl-alpha-D-glucopyranosyl bromide yields 2,3,4-tri-O-benzyl- (9), 2,3,4-tri-O acetyl- (10), and 2,3,4-tri-O-benzoyl-N-(2,2-diethoxycarbonylvinyl)-6-O-(2,3,4,6 tet ra-O- acetyl-beta-D-glucopyranosyl)-beta-D-glucopyranosylamine (11), respectively. 2,3,4-Tri-O-benzyl- (6), 2,3,4-tri-O-acetyl- (7), and 2,3,4-tri-O- benzoyl-N-(2,2-diethoxycarbonylvinyl)-beta-D-glucopyranosylamine (8) are also described. PMID- 1423351 TI - Synthesis of the antibiotic cortalcerone from D-glucose using pyranose 2-oxidase and a novel fungal enzyme, aldos-2-ulose dehydratase. AB - Using two enzymes purified from the white-rot fungus, Polyporus obtusus, 5% solutions of D-glucose have been quantitatively converted in vitro into D-arabino hexos-2-ulose (D-glucosone) and subsequently into a compound having antimicrobial activity. The antibiotic has been shown by nuclear magnetic resonance and mass spectroscopy to be chemically identical to a previously described fungal metabolite known as cortalcerone. Based on kinetic analysis of the synthetic process, a pathway for the biosynthesis of cortalcerone is proposed, involving both chemical rearrangement and enzymically catalyzed steps. Two enzymes, pyranose 2-oxidase and a previously uncharacterized D-arabino-hexos-2-ulose utilizing enzyme, may be sufficient for the biosynthesis of cortalcerone from glucose in vivo. The D-arabino-hexos-2-ulose-utilizing enzyme dehydrates certain aldosuloses and has been named aldos-2-ulose dehydratase. The enzyme, which appears to be a dimer of 95-kDa subunits, has been purified 450-fold. Additional properties of aldos-2-ulose dehydratase are described, including its apparent ability to catalyze two different steps in the proposed biosynthetic pathway for cortalcerone. PMID- 1423352 TI - Studies of the interaction of the maltose-binding protein of Escherichia coli, a closed-groove binder, with 4,6-O-ethylidenemalto-oligosaccharides (dp 2-5) and its regioselective labelling with 3-azibutyl 1-thio-alpha-(6-3H)maltoside. AB - Four malto-oligosaccharides (dp 2-5), each with a 4,6-O-ethylidene group on the glucosyl unit at the non-reducing terminus, were synthesised and used to prove that the maltose-binding protein (MBP) of E. coli is a closed-groove binder. alpha-D-Glucosylation of 3-azibutyl 1-thio-alpha-D-(6-3H)glucopyranoside yielded a 3H-labelled, photolabile 1-thiomaltoside derivative that was used to chemically modify the binding site of MBP. The 3H-labelled peptide containing 83% of the total radioactivity, which was isolated after tryptic cleavage of the modified MBP and sequenced, is part of the closed end of the MBP groove. PMID- 1423353 TI - Synthesis of 4'-deoxy-4'-fluorokanamycin A and B. AB - 4'-Deoxy-4'-fluorokanamycins A (17) and B (25) have been prepared through fluorinative ring-opening of the D-galacto-3',4'-oxiranes (8 and 21) derived from kanamycin A and B with potassium hydrogenfluoride in ethane-1,2-diol. The mechanism of preponderant formation of the 4'-deoxy-4'-fluoro-D-gluco (9 and 22) over the 3'-deoxy-3'-fluoro-D-gulo derivatives was discussed. In the synthesis of 25, the unusual 3',6'-epimine (23) was the main product along with the 4'-deoxy 4'-fluoro derivative. The mechanism of this reaction is also discussed. Both 17 and 25 were active against resistant bacteria producing aminoglycoside adenylylating enzymes for HO-4'. PMID- 1423354 TI - Crystal structure of lactitol (4-O-beta-D-galactopyranosyl-D-glucitol) trihydrate. AB - Lactitol trihydrate, C12H24O11.3H2O, crystallises in the orthorhombic space group, P2(1)2(1)2(1) with cell dimensions a = 8.306(2), b = 10.163(1), c = 21.321(1) A, and V = 1799.8(5) A3; Z = 4, Dx = 1.47 Mg m-3, lambda(Cu-K alpha) = 1.54178 A, mu = 1.14 mm-1, F(000) = 856, and T = 23 degrees. There are one intra- and thirteen inter-molecular hydrogen bonds in the structure. The bond lengths and angles agree well with the mean values of related structures. The galactopyranosyl ring has a chair conformation. PMID- 1423355 TI - The crystal structure and physicochemical properties of L-ascorbic acid 2 glucoside. AB - The stable L-ascorbic acid glucoside produced by the action of the cyclomaltodextrin glucanotransferase (CGTase, EC 2.4.1.19) from Bacillus stearothermophilus was crystallized from an aqueous solution. Determination of the molecular structure by single crystal X-ray analysis showed the compound to be 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G). The crystals are orthorhombic, space group P2(1)2(1)2(1), with unit-cell dimensions a = 11.929 A, b = 24.351 A, and c = 4.864 A. The D-glucopyranose residue has the 4C1 conformation. These conclusions are in good agreement with those based on the 13C NMR spectrum. The general physicochemical properties of crystalline AA-2G are reported. PMID- 1423356 TI - Studies of the molecular recognition of synthetic methyl beta-lactoside analogues by Ricinus communis agglutinin. AB - The 2-, 3-, 6-, 2'-, 3'-, 4'-, and 6'-deoxy derivatives and the 3-O-methyl derivative of methyl beta-lactoside have been synthesised and their binding to the galactose-specific agglutinin from Ricinus communis (RCA-120) has been investigated. The results indicate that HO-3,4,6 of the beta-D-galactopyranose moiety are the key polar groups. The main difference from the closely related ricin lectin RCA-60 involves HO-6 of the D-glucopyranose moiety, which seems to contribute to the binding of the carbohydrate to RCA-60 but not to RCA-120. PMID- 1423357 TI - Investigation of the active site of Escherichia coli beta-D-galactosidase by photoaffinity labelling. AB - 3,7-Anhydro-2-azi-1,2-dideoxy-D-glycero-L-manno-(8-3H)octitol++ + (1a) and 3 azibutyl 1-thio-beta-D-(6-3H)galactopyranoside (2a) were synthesised from the unlabelled compounds by reaction with galactose oxidase, then reduction with sodium borotritide. Whereas 1a was an efficient photoaffinity reagent for the beta-D-galactosidase from E. coli, 2a was ineffective. Three 3H-labelled peptides were isolated after digestion of the labelled enzyme with trypsin, one of which was an octapeptide (Trp 158 to Ser 165), which is remote from the segments detected as part of the active site of the enzyme. PMID- 1423358 TI - Oxazolidines from sugars: conformationally restricted derivatives of muramic acid. PMID- 1423359 TI - Redox glycosidation: the use of Nozaki-Takai methylenylation in a highly stereoselective synthesis of sucrose. AB - Sequential reaction of 2,3,4,6-tetra-O-benzyl-D-glucopyranose (7) with butyllithium and 2-[2,3,5-tri-O-benzyl-4-O-(tert-butyldiphenylsilyl)-D- arabinonoyl]thio-3-nitropyridine (6) at -78 degrees gave 2,3,4,6-tetra-O-benzyl alpha-D-glucopyranosyl 2,3,5-tri-O-benzyl-4-O-(tert-butyldiphenylsilyl)-D arabinonate+ ++ (8; 71%, alpha:beta greater than 50:1). Ester carbonyl methylenylation, desilylation, and iodoetherification in the presence of silica gave 3,4,6-tri-O-benzyl-1-deoxy-1-iodo-(2,3,4,6-tetra-O-benzyl-alpha-D- glucopyranosyl)-beta-D-fructofuranoside (15; 44%, alpha:beta greater than 50:1). This neopentylic iodide 15 was converted into sucrose (1;80%) by free-radical substitution using TEMPO (24) followed by sodium-ammonia reduction, acetylation, and Zemplen methanolysis. PMID- 1423360 TI - Synthesis of 5-deoxy-5-fluoro and 5-deoxy-5,5-difluoro derivatives of kanamycin B and its analogs. Study on structure-toxicity relationships. AB - 5-Deoxy-5-fluoro- (1), 5.3'-dideoxy-5-fluoro- (2), and 5,3',4'-trideoxy-5-fluoro kanamycin B (3) have been prepared by treatment of 5-epihydroxyl precursors (prepared by the Mitsunobu reaction) with DAST as the key step. 5,3'-Dideoxy-5,5 difluoro- (26) and 5,3',4'-trideoxy-5,5-difluoro-kanamycin B (27) were also prepared by treatment of the corresponding 5-oxo derivatives with DAST. These 5 deoxy-5-fluoro and 5-deoxy-5,5-difluoro derivatives showed markedly decreased toxicity as compared with the parent compounds. PMID- 1423361 TI - Apple-fruit xyloglucans: a comparative study of enzyme digests of whole cell walls and of alkali-extracted xyloglucans. AB - Apple cell walls or alkali-extracted xyloglucans were digested with an endo glucanase from Trichoderma viride and the resulting oligosaccharides were isolated by chromatography on Bio-Gel P-4. Three main oligosaccharides were present in similar proportions, and their structures were shown to be [Xyl(Glc)]3 Glc, [Xyl(Glc)]2-(FucGalXyl)Glc-Glc, and XylGlc-(GalXyP)Glc-(FucGalXyl)Glc-Glc. Each non-reducing-end Glc was 6-linked, each reducing-end Glc was 4-substituted, and each other Glc was 4,6-disubstituted. The Xyl was either terminal or 2 substituted, the Fuc was terminal, and the Gal was either terminal or 2 substituted. The 1H-NMR spectra of the oligosaccharides extracted directly from the cell wall showed that they are not acetylated. Other oligosaccharides, notably GalXyl3Glc4, Xyl2Glc4, and Xyl2Glc3, were present in smaller proportions in the digest of the cell walls. PMID- 1423362 TI - Conformational analysis of the trisaccharide components of the repeating units of the capsular polysaccharides of Streptococcus pneumoniae types 19F and 19A. PMID- 1423363 TI - Mechanism of the adsorption of pancreatic alpha-amylase onto starch crystallites. PMID- 1423364 TI - O-(3-butenyl), a stable blocking group removable by ozonolysis. PMID- 1423365 TI - [Better efficacy of K-strophanthidin versus digoxin in subjects with dilated cardiomyopathy and chronic heart insufficiency]. AB - We evaluated the efficacy of K-strophanthidin and digoxin in 20 patients with stable, severe congestive heart failure. In this aim, we studied the left ventricular pump function at rest and following manipulation of the cardiac load (cold pressor test and nitroprusside infusion), the exercise performance (cardiopulmonary exercise test), and the level of circulating norepinephrine. The study was double-blind and cross-over and comprehended 4 periods of 1-week each during which patients received in random order: placebo (oral+intravenous), K strophanthidin (intravenous + oral placebo), digoxin (oral+intravenous placebo and, in 8 patients, intravenous + oral placebo). The efficacy of the various compounds was tested at the end of each period 1 and 10 hours after drug dosing. Comparable results were obtained by the 2 sets of measurements. Both digoxin and K-strophanthidin showed a positive inotropic effect. This is shown by an upward shift of the ejection fraction/end-systolic stress. In spite of this, only K strophanthidin significantly increased exercise performance: tolerance time (+153 s), peak oxygen consumption (+1.2 ml/kg/min) and oxygen consumption at anaerobic threshold (+2.3 ml/kg/min). Norepinephrine plasma level at rest was significantly lowered only by K-strophanthidin. Results were comparable when digoxin was given intravenously. We conclude that both glycosides elicit an increase of the inotropic cardiac state but only K-strophanthidin improves exercise performance. PMID- 1423366 TI - [Importance of late reversibility in the identification of myocardial viability at risk after myocardial infarction]. AB - The prevalence of late reversibility in single photon emission computed tomography (SPECT) thallium 201 stress/redistribution studies is still controversial. The aim of our work was to evaluate the prevalence of late reversibility at infarct site in an unselected population of patients with previous acute myocardial infarction (AMI). We studied by SPECT thallium 201 and pharmacologic stress with dipyridamole (DIP) as well as by two-dimensional echocardiography 58 consecutive patients with previous AMI (50 men of mean age 57 years, range 40-73; 8 women of mean age 58 years, range 50-68). All the patients with perfusion defect at infarct site that was persistent at 4-hour study, were reimaged after 24 hours. Twenty-one (36%) of 58 patients complained about postinfarction angina. Following intravenous DIP (0.56 mg/kg), heart rate increased from 67 +/- 14 to 83 +/- 14 b/min (< 0.0001) and diastolic and systolic arterial pressures dropped from 86 +/- 12 and 139 +/- 25 mmHg to 79 +/- 14 and 132 +/- 27 mmHg, respectively (< 0.0001; < 0.0005). Of 57 patients with stress perfusion defects at infarct site, 16 (28%) demonstrated reversibility after 4 hours and 19 (33.4%) after 24 hours, with a total of 35 (61.4%) patients demonstrating reversibility by combined 4-hour and 24-hour imaging (< 0.0001 versus reversibility at 4-hour imaging alone). Thus, of 41 patients with 4-hour persistent thallium defects at infarct site, 19 (46.3%) demonstrated late reversibility.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423367 TI - [Early isovolumetric relaxation: correlation with the densitometric analysis of coronary stenosis]. AB - Early relaxation is characterized by a segmental outward wall movement during isovolumic relaxation. There is still no general agreement as to its significance. Some Authors have considered the phenomenon to be a specific marker of isolated coronary narrowing, others have regarded it as a normal variation of left ventricular relaxation and still others concluded that it is a compensatory phenomenon to local ischemia in another region. We used a method of quantitative assessment of regional left ventricular function and a videodensitometric analysis of coronary stenosis. In our study we didn't observe an improved systolic function of the regions that presented early relaxation, but a slight non significant reduction. We did neither observe any correlation between early relaxation and ischemia provoked by stress test nor between early relaxation and coronary artery disease. The amplitude of early relaxation was not statistically different between patients with and without stenosis of left anterior descending artery. We conclude that early relaxation is a normal variation of left ventricular relaxation. PMID- 1423368 TI - [Lipids and serum apoproteins in subjects with slight or mild coronary atherosclerosis evaluated with angiography]. AB - In this study 126 subjects (91 males and 35 females, range of age 43-65 years) were studied by coronary angiography. We considered positive for coronary atherosclerosis also patients showing mild or moderate stenosis (> or = 25%). In all subjects we have evaluated serum lipid and apoprotein A-I, B, C-II, C-III and E levels; therefore also cholesterol concentrations in all lipoprotein fractions, separated by sequential ultracentrifugation (VLDL d < 1.006, LDL d 1.006-1.063, HDL d > 1.063 g/ml) and apoprotein B in LDL have been measured. Subjects with coronary atherosclerosis have shown significantly higher levels of total cholesterol, LDL-cholesterol, total cholesterol/HDL-cholesterol and LDL cholesterol/HDL-cholesterol ratios than controls. Therefore, a lower apo A-I/apo B ratio in males and a higher LDL-apo B levels in females has been found in subjects with coronary atherosclerosis in comparison with controls. The stepwise multiple analysis has demonstrated that LDL-cholesterol levels is the parameter that best correlates with the presence of coronary atherosclerosis. These data confirm the importance of the reduction of LDL-cholesterol levels in primary and secondary prevention of coronary heart disease. PMID- 1423369 TI - [The use of the inferior epigastric artery as alternative conduit for myocardial revascularization: our experience]. AB - When complete revascularization can not be obtained with the internal mammary artery and saphenous veins, the inferior epigastric artery may be an excellent alternative conduit. We describe our experience with this conduit, review the anatomy of this artery, and present the evolution of our harvesting technique through a pararettal approach. Proximal anastomoses were made first with the aid of an oval cuff of the common femoral artery (5 cases, Group A). Two patients (40%) of this group studied postoperatively revealed a graft occlusion. In the last 13 cases (Group B) we tailored the proximal anastomoses directly to the aorta. All patients studied postoperatively showed patent inferior epigastric artery grafts. There were no hernias and no deaths. Inferior epigastric artery can be considered a good alternative conduit in myocardial revascularization. PMID- 1423370 TI - [Phase 3 and phase 4 bundle of branch block]. AB - Intermittent left bundle branch blocks are present in the ECGs of 1 patient with mitral valve disease. By occurring either after short or long cycles they represent respectively phase 3 and phase 4 blocks. Such mechanisms emphasize the relationship between automatism and conduction. The occurrence of block and of normal conduction during cycles of the same length, its correlation with the conduction of the previous cycle, demonstrate the presence of a functional linking between successive impulses. This linking may occur every time a potential or active macroreentry circuit exist. In our case the circuit is formed by the 2 bundle branches which join distally in the ventricular septum. PMID- 1423371 TI - [Critical mitral stenosis in pregnancy: description of a case treated with percutaneous valvuloplasty]. AB - We report the case of a 26-year-old woman who underwent mitral valvuloplasty during the 23rd week of gestation, following an episode of pulmonary edema. Dilation, performed without complications, increased mitral valve area from 0.9 to 1.8 cm2, cardiac output from 4.8 to 5.9 l/min, and decreased mean transvalvular gradient from 13.2 to 5 mmHg. The patient delivered spontaneously a full-term normal baby. Echocardiographic evaluation at 6 months confirmed the persistency of procedure's good outcome. According to some Authors and to our results it can be inferred that mitral valvuloplasty is a feasible and effective treatment for critical mitral stenosis during pregnancy. PMID- 1423372 TI - [Mitochondrial myopathy and the heart. Kearns-Sayre syndrome]. PMID- 1423373 TI - The invention and reinvention of cardiac pacing. AB - Two primitive pacemakers were invented between 1925 and 1932, demonstrating that adequate knowledge existed to pace the heart for brief periods. Heart specialists ignored these interesting inventions. In contrast, Zoll's announcement of external pacing in 1952 spurred intense interest and an outpouring of research. The reasons for the different response of heart specialists in the 1950s have to do with improved medical understanding of cardiac arrhythmias, growing confidence that cardiac resuscitation was possible, and the expansion of hospital-based medicine after World War II. PMID- 1423375 TI - Timing cycles of permanent pacemakers. AB - A clear understanding of the components of the pacemaker timing cycles is crucial to understanding and interpreting paced electrocardiograms. The information given in this article provides basic rules for timing cycles for pacing modes currently in use and pacing modes less frequently used but of importance in understanding current timing cycles. Although understanding basic timing cycles allows interpretation of most paced electrocardiograms, manufacturer-dependent variations of the timing cycle operation make it necessary to be intimately familiar with the design of each pacemaker to be interpreted. PMID- 1423374 TI - Cardiac pacing in special and complex situations. Indications and modes of stimulation. AB - This article reviews a variety of pacing options for those patients with special and complex situations. Syndromes and syncopes, cardiomyopathy, and coronary artery disease are reviewed. Pacing modes are also discussed. PMID- 1423376 TI - Cardiac pacing and atrial arrhythmias. AB - Pacemaker patients frequently have concomitant atrial tachyarrhythmias, most importantly atrial fibrillation, because numerous underlying electrical or structural diseases can potentiate both conditions. DDD pacing (or atrial) appears superior to VVI in limiting the occurrence of atrial fibrillation and its associated negative sequela. Sick sinus syndrome, a prior history of atrial fibrillation, and advanced age predispose patients with DDD devices to postimplant atrial fibrillation, yet the majority of these high-risk patients are manageable in DDD throughout their follow-up. DDD patients at significant risk for developing atrial arrhythmias require special attention regarding the selection and programming of their devices. Rate modulation, higher lower rate limits, special approaches toward upper rate limit management, and antitachycardia capabilities may all be important aspects in their management. The combined use of AV node ablation and ventricular or DDD pacing to manage patients with refractory atrial tachyarrhythmias is becoming an increasingly accepted therapeutic approach. PMID- 1423377 TI - Physiology of rate-responsive pacing. AB - The search for a pacemaker that accurately and easily mimics normal physiology is a continuing effort. There have been many achievements in the past, including sensing of the pacing chamber and programming of the pacing rate, sensitivity, and output. Present pacing developments include atrioventricular synchrony and rate adaptiveness. Results of studies on activation sequence and circadian variations will impact future pacing. The usefulness, cost effectiveness, and clinical value of some of the new pacing features remain unclear. Further clinical trials are necessary to clarify the value of new pacing techniques. PMID- 1423378 TI - Comparison of two activity-controlled rate-adaptive pacing principles: acceleration versus vibration. AB - Activity-guided rate-adaptive pacing is currently the most widely used principle for rate adaptation. Broad experience has been gathered from several hundred thousand pacemakers that adjust the pacing rate according to vibrational forces detected by a piezosensor bonded to the inner side of the pacemaker can. A new generation of accelerometer-based pacemakers has been introduced into clinical practice. The vibrational type detects vibration, pressure, and shock waves traveling through the body with physical stress and using the pacemaker can as a resonator. In contrast, the accelerometer is insulated from the pacemaker housing and is incorporated into electronic hybrid circuitry. The forces detected by an accelerometer are motion and acceleration of the body in an anterior-posterior direction. Clinical studies conducted to date have shown that the accelerometer to be superior to the conventional vibration activity pacemakers, as far as the discrimination of different workloads and rejection of unwanted environmental noise are concerned. PMID- 1423379 TI - Rate-responsive pacing using electrographic parameters as sensors. AB - The use of evoked QT-interval and ventricular depolarization gradient as sensors for rate-responsive pacing is described in this article. The QT interval has been used as a biosensor in implantable pacemakers since 1981, and recent refinements have improved the rate response characteristics and simplified the programming of this pacemaker. Recently, QT and activity sensing have been combined to produce a dual-sensor rate-responsive pacemaker that may offer advantages over single sensor devices. The ventricular depolarization gradient has been incorporated into a closed-loop rate-responsive pacing system and is undergoing clinical evaluation. PMID- 1423380 TI - Adaptive-rate pacemakers. Comparison of sensors and clinical experience. AB - Many types of artificial sensors for adaptive-rate pacing have appeared but as yet there is no single sensor that properly reflects metabolic demand under all circumstances. Several other types of sensors are currently evaluated. Combinations of different sensors in a single unit are very promising. At present, however, the only completely satisfactory sensor is the normal sinus node. PMID- 1423381 TI - Survival in patients with permanent pacemakers. AB - Atrioventricular block I has a benign natural course, and permanent pacing is not warranted. Second-degree AV block, including both type I and type II, can have an ominous course, especially in older patients with underlying heart disease. One study claims that the prognosis in patients with second-degree AV block, irrespective of type, is improved by permanent pacing. In spite of lack of controlled studies it has been convincingly shown that VVI pacing prolongs life in patients with high-grade AV block. Two studies suggest that atrial synchronous pacing in patients with congestive heart failure and high-grade AV block might improve their survival. Studies comparing survival with different pacing modes in patients with sinus node disease support the hypothesis that physiologic pacing can improve survival. Prophylactic pacemaker implantation even in symptomatic patients with chronic bifascicular block does not seem to protect them from sudden death. PMID- 1423382 TI - Exercise testing for chronotropic assessment. AB - Cardiac chronotropic analysis has only begun to develop into a clinically relevant science. In the past, formal exercise testing was usually relegated to the assessment of ischemia or cardiac rehabilitation. The establishment of rate responsive pacemakers as a potentially effective treatment for chronotropic incompetence forced the definition of cardiac chronotropism and assessment of the pacemaker response. Little is known about the normal chronotropic response and less has been established about patients with ventricular dysfunction or ischemia, but standards are being set and modern pacemakers have produced the ideal clinical laboratory for investigation. Advanced telemetry, including sensor and actual rate trends, histography and sensorgraphy produce previously unobtainable clinical data. Now scientific inquiry demands that chronotropic evaluations seek to match the pacemaker-augmented response of the chronotropically incompetent patient to the metabolic requirements of the body. Only with formal exercise testing will this goal be achieved. PMID- 1423383 TI - Strategies for mode selection in antibradyarrhythmia pacing. AB - A systematic technique is described for selecting an appropriate mode of antibradycardia pacing on the basis of 10 clinical criteria. A computer model of the selection process was developed with input from more than 41 implanting physicians, and implemented together with a database management system for keeping track of mode selections and identifying cases in which the modes selected by the implanters differed from those recommended by the model. The selection technique, which can be used without a computer, is presented in detail with a decision-tree representation of the model and an explanation of the rationale behind each of its 39 possible recommendations. PMID- 1423384 TI - Lead extraction. Indications and techniques. AB - Each of the extraction techniques and their ancillary tools was reported as used successfully; however, until now, no technique has been successful when used in more than a few isolated instances. The technique for intravascular countertraction and the associated tools described in this paper were devised and selected in an attempt to develop one technique to be used on all patients, with all types of leads, and with a very low complication rate. Its versatility permitted single or multiple lead extractions combined with the precision of selecting and extracting a specific lead. In our experience, as well as the experience of others, the techniques described in this paper have proved to be superior by minimizing the inherent risk and morbidity, allowing us to expand the indications for lead removal beyond septicemia and free-floating leads, to include infection, abandonment of pockets, and replacement of malfunctioning or fractured leads. Intravascular countertraction was a consistently safe and efficacious method of removing transvenous pacemaker leads regardless of the duration of the implant, thus permitting extractions in patients not considered candidates for a more extensive surgical procedure. Intravascular countertraction encompasses surgical and fluoroscopic techniques possessed by most physicians experienced in pacemaker and automatic implantable cardioverter defibrillator implants. However, there is a learning curve, predicating caution for the inexperienced physician. In addition, advanced surgical skills may be needed in handling associated conditions such as debridement and primary closure of chronically inflamed tissues, especially in submuscular pockets and sinus tracts in the neck. Although the potential for a cardiovascular complication is small, it does exist, and cardiovascular surgical backup is a recommended precaution. PMID- 1423385 TI - Pediatric cardiac pacing. AB - Cardiac pacing in children has undergone many improvements in the last decade. The differences between adult and pediatric pacing have narrowed. Children are no longer being denied pacemakers because of size. This article discusses techniques for pacing pediatric patients successfully that will allow them to lead normal lives. PMID- 1423386 TI - Historical overview on the development and characteristics of stents and future outlooks. AB - The history and development of endovascular stents is described beginning with the Maass double helix spiral prosthesis, the first stent used in human clinical trials in the early 80s. This is followed by a description of the three main groups of stent techniques: the shape memory alloy stents, the balloon-expandable stents, and the self-expanding stainless steel stents. Requirements and new trends for improving clinical results in the future complete this text. PMID- 1423387 TI - Intravascular stenting: from basic research to clinical application. AB - Although the use of intravascular stents is approaching widespread clinical use, several questions remain regarding their safety and efficacy. Several factors have direct bearing on the immediate and long-term results of intravascular stenting. The technical results of stenting are dependent on the mechanical characteristics of the device and long-term patency is closely related to thrombogenicity and endothelialization. Although stents are used most frequently for the treatment of atherosclerotic disease there is no clear understanding of how they influence the atheromatous lesion. PMID- 1423388 TI - Stent placement in iliac arterial lesions: three years of clinical experience with the Wallstent. AB - Within a 3-year period, 125 patients with 63 iliac occlusions and 62 complex iliac stenoses underwent stent placement using self-expandable vascular endoprostheses. Early technical success rate was 98%, with a total complication rate of 4%. Major complications were seen in 1.6%. Early reobstruction occurred in 4 patients with previous occlusions. Late reobstruction due to a clinically relevant restenosis or reocclusion occurred in 10 patients and required 12 repeat interventional procedures. Cumulative patency, excluding early technical failure, was 100% at 6 months and 89.4% at 24 months. Stenting of iliac arteries using self-expandable endoprostheses is a safe and effective treatment of complex iliac lesions. PMID- 1423389 TI - Stenting of the iliac arteries with the Palmaz stent: experience from a multicenter trial. AB - Balloon-expandable, intraluminal stenting of the iliac arteries with the Palmaz stent was the subject of a multicenter study for 4 years. A total of 486 patients underwent 587 procedures. Four hundred and five patients had unilateral and 81 had bilateral iliac stent placements. Follow-up ranged from 1 to 48 months (mean 13.3 +/- 11 months). Sustained clinical benefit of the treated patients was obtained in 90.9% at 1 year, 84.1% at 2 years, and 68.6% at 43 months. Angiographic patency rate was 92%. Diabetes mellitus and poor runoff had significant negative influence on the clinical outcome. The 10% incidence of procedural complications was not altered by operator experience. PMID- 1423390 TI - The Strecker stent: indications and results in iliac and femoropopliteal arteries. AB - We have implanted more than 100 Strecker stents in the iliac and femoral arteries. In iliac arteries, follow-up is available from 8 to 48 months (mean 20 months) and in peripheral arteries, from 8 to 32 months (mean 19 months). In iliac and proximal femoral arteries there was a patency rate of 98% (mean 20 months after stent implantation) whereas in peripheral arteries the patency rate was 70.8% (mean 19 months after stent implantation). Besides careful selection of patients, anticoagulation is very important for successful stenting. Because of the excellent results of stents in iliac vessels there is a wide range of good indications, including primary stenting after recanalization of occlusions. In contrast, stent implantation in peripheral vessels should be restricted to special cases such as acute dissection or reocclusion after successful recanalization. PMID- 1423391 TI - A comparison study of self-expandable stents vs balloon angioplasty alone in femoropopliteal artery occlusions. AB - In a group of 26 patients percutaneous transluminal (balloon) angioplasty (PTA) and stents (Wallstents) were applied and in another 26 matched patients PTA alone was used as primary treatment for femoropopliteal occlusions of 3 cm or longer. Five patients with stents showed early thrombosis necessitating catheter thrombolysis and/or thrombus aspiration. Ten patients had recurrent stenoses within 12 months, mostly due to neointimal hyperplasia. Following three late catheter reinterventions, a cumulative secondary patency rate of 69% was achieved after 12 months. The group of patients treated by PTA alone showed a 12 months patency rate of 65% without reinterventions. In 8 other patients, stents were inserted for recurrent obstructive or PTA-resistant lesions, and similar results as with the stents above were obtained. Thus, these stents do not improve primary results of PTA in femoropopliteal occlusions but may be useful secondarily after unsuccessful PTA. PMID- 1423393 TI - Gianturco-Rosch expandable Z-stents in the treatment of superior vena cava syndrome. AB - Gianturco-Rosch expandable Z-stents were used in 22 patients with superior vena cava syndrome (SVCS). Stents were placed in all patients in the SVC and in 17 patients, also into the innominate veins. Stent placement resulted in complete relief of symptoms in all patients. Twenty-one patients had no SVCS recurrence from 1 to 16 months, to their death, or to the present time. SVCS recurred only in 1 patient 9 months after stent placement due to tumor ingrowth and secondary thrombosis. Based on ours and on other reported experiences, expandable metallic stents are effective devices for treatment of the SVCS which is difficult to manage by other means. PMID- 1423392 TI - Midterm results of renal artery stenting. AB - Percutaneous transluminal angioplasty (PTA) has become the treatment of choice for major renal artery stenosis. Nonetheless, about 10% of renal artery stenoses cannot be properly dilated, and among the patients successfully dilated, 10%-15% had a recurrence. Renal artery stenting was used in 21 patients in cases of insufficient results after PTA: persisting significant stenosis after a primary or several PTAs (15 cases), recurrences (9 cases). Follow-up in all patients was from 12 months to 4 years. Implantation was performed without any problems but the low radioopacity of the stent makes placement difficult in obese patients, particularly for ostial lesions. There was no major complication except occlusion of a segmental branch of the renal artery in 1 case. Radiological controls have shown a preserved patency in all cases except 2, which present restenosis inside the stent by intimal hyperplasia. A significant clinical improvement was obtained in 90% of cases. These results suggest that the endovascular prosthesis represents an important adjunct to renal PTA. PMID- 1423394 TI - Gianturco self-expanding stents: clinical experience in the vena cava and large veins. AB - Twenty-five patients with stenosis of the vena cava (21) and other large veins (4) have been treated with self-expanding Gianturco metallic stents. Eighteen patients had superior vena cava syndrome. In 17, the stricture was due to malignant superior vena cava compression recurrent after maximum tolerance radiotherapy and/or chemotherapy. In 16 of these patients there was early symptomatic relief. In 1 patient with a benign posttraumatic superior vena cava stricture, the stenosis was not relieved, and occlusion occurred after 1 month. Stenoses associated with dialysis shunts were relieved in 2 other patients. Two malignant and one benign inferior vena cava stenoses were relieved either until death, or in the benign case, for 30 months. One malignant subclavian vein obstruction occluded after 24 h due to stent misplacement and another with extrinsic mediastinal compression remained patent until death, extensive thrombus having been lysed prior to stent placement. The results of this short series suggest that the Gianturco self-expanding stent in the vena cava and large veins is easy and safe to place, and in most cases produces almost immediate palliation of the distressing effects of venous obstruction, often in a preterminal and inoperable patient. PMID- 1423395 TI - Use of the Wallstent in the venous system including hemodialysis-related stenoses. AB - Eighteen patients with a total of 23 venous stenoses or occlusions were treated with the Wallstent. In 5 patients treated for malignant stenosis there was one primary failure due to insufficient stent expansion. The other 4 patients showed rapid relief of their inflow obstruction, all remaining asymptomatic despite later stent occlusion in 1 patient. Four patients were treated for benign postoperative stenoses of the iliac or femoral vein. All stents remained patent for a period of 6 weeks-58 months. Nine patients were treated for one or multiple stenoses along the venous outflow tract of hemodialysis fistulas. Of 14 lesions that were eventually stented, 12 are still patent after 3-27 months (mean 19). However, 10 secondary interventions (eight percutaneous transluminal angioplasty (PTA), two stents) and three additional stent procedures for new lesions were necessary. Although our experience is limited, we believe that patients with tumor compression or postoperative strictures of large veins benefit from treatment with stents. Stenting of venous outflow stenoses in hemodialysis fistulas can significantly prolong stent function, however, PTA should always be the first treatment of choice. PMID- 1423397 TI - A consultation. PMID- 1423398 TI - A permanently bondable matrix band for composite restorations. PMID- 1423396 TI - Morphologic and clinical results of the transjugular intrahepatic portosystemic stent-shunt (TIPSS). AB - The concept of transjugular intrahepatic portosystemic stent-assisted shunt (TIPSS) using the Palmaz iliac stent has been successfully accomplished in 18 of 24 patients representing a technical success rate of 75%. Fourteen were male, 4 female with a mean age of 60 years (range 34-84 years). According to classification of Child's and Turcotte, 6 were in stage A, 6 in stage B, and 6 in stage C. Five patients were treated on an emergency basis because of massive active bleeding. In 10 patients the portosystemic tract was created between the middle hepatic vein and the right main stem of the portal vein in 8, and the left main stem in 2 patients. In 8 patients, the shunt was established between the right hepatic vein and the right main branch of the portal vein. The portosystemic gradient in 18 patients was 29.9 +/- 6 mm Hg and dropped to an average of 16.9 +/- 4 mm Hg after shunt establishment. Within the early postprocedural period of 30 days, 1 patient died of direct complications of the procedure. Because of catheter dislocation, embolization of the percutaneous transhepatic approach to the portal vein after successful shunt "creation" could not be done and was followed by intraabdominal exsanguination. One patient died of an ARDS after TIPSS. A third developed pulmonary infection. In 13 patients, because of hematomas at the puncture site of the transhepatic approach, only the transjugular approach was elected for establishing TIPSS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423399 TI - Periodontal disease in the life stages of women. PMID- 1423400 TI - Diagnostic anesthesia for referred trigeminal pain: 1. PMID- 1423401 TI - Applications of oxidized regenerated cellulose in periodontal therapy: Part 1. PMID- 1423402 TI - Sequelae of occlusal rest loss: a case report. PMID- 1423403 TI - Differential diagnosis of localized soft-tissue tumefactions of the tongue. PMID- 1423404 TI - Electronic spreadsheets--tools for profit. PMID- 1423405 TI - Morphea: a localized scleroderma, with en coup de sabre. PMID- 1423406 TI - The top 20 prescription drugs and how they affect your dental practice. PMID- 1423407 TI - A clinical comparison of three overdenture anchors. PMID- 1423408 TI - Hepatitis B and hepatitis C: what you should know. PMID- 1423409 TI - Phenytoin-induced gingival overgrowth: a case report. PMID- 1423410 TI - A cost analysis for handpiece infection control: autoclave vs hydrogen peroxide vapor sterilization. PMID- 1423411 TI - The forensic dental report. PMID- 1423412 TI - Functional implications of spontaneous sarcoplasmic reticulum Ca2+ release in the heart. AB - The Cai oscillation generated by the sarcoplasmic reticulum in response to an action potential occurs relatively synchronously within and among cells. The sarcoplasmic reticulum can also generate spontaneous Cai oscillations (S-CaOs), ie, not triggered by sarcolemmal depolarisation. The local increase in Cai due to S-CaOs is equivalent to that induced by an action potential. Heterogeneity of diastolic Cai among cells within myocardial tissue caused by asynchronous S-CaOs leads to heterogeneous myofilament activation, the summation of which produces a Ca2+ dependent component to diastolic tone. The local increases in Cai due to S CaOs also cause oscillatory sarcolemmal depolarisations due to Ca2+ modulation of the Na-Ca exchanger and of non-specific cation channels. When local S-CaOs within a myocardial cell is sufficiently synchronised the resultant depolarisation summates and can be sufficient to trigger a spontaneous action potential. Inhomogeneous levels of diastolic Cai among cells may lead to heterogeneity in cell coupling and thus may also affect the impulse conduction in myocardial tissue. The magnitude of the S-CaOs induced diastolic tonus and depolarisation varies with the extent to which S-CaOs are synchronised; partially synchronised S CaOs following an action potential induced Ca2+ release produce an aftercontraction and afterdepolarisation. Inhomogeneity of diastolic sarcoplasmic reticulum Ca2+ loading and sarcomere lengths within individual cardiac cells due to S-CaOs leads to inhomogeneous systolic Cai levels and sarcomere inhomogeneities in response to a subsequent action potential, which compromise the systolic contraction amplitude. Heterogeneity of systolic Cai among cells due to diastolic S-CaOs also leads to heterogeneity of action potential repolarisation times, due to heterogeneous Cai modulation of the Na-Ca exchanger, the non-specific cation channel, the L type Ca2+ channel and, depending upon species, Ca2+ activated K+ channels. S-CaOs occurrence during a long action potential plateau may also modulate the removal of voltage inactivation of L type Ca2+ channels, and affects the likelihood of the occurrence of "early afterdepolarisations." Thus, as a single entity, S-CaOs may be implicated in diverse manifestation of heart failure--impaired systolic performance, increased diastolic tonus, and an increased probability for the occurrence of arrhythmias. PMID- 1423413 TI - Engineering and physiological approaches to the study of cardiovascular function: science and pseudoscience? PMID- 1423414 TI - Engineering and physiological approaches to the study of cardiovascular function: alternative or complementary? PMID- 1423415 TI - Differential effects of left anterior descending coronary occlusion on left and right ventricular anterior wall thickening in the conscious pig. AB - OBJECTIVE: In humans, the left anterior descending coronary artery supplies the left ventricular wall, anterior septum and the paraseptal part of the right ventricular anterior wall. Our aim was to study the effects of acute left anterior descending coronary occlusion on wall thickening in the regions of the left and right ventricular anterior walls supplied by the artery, and in remote, non-ischaemic regions of both ventricles. METHODS: Systolic wall thickening (defined as percent thickening with respect to end diastolic wall thickness) was studied in eight conscious pigs every 15 s during 1 min of acute left anterior descending coronary occlusion by a cuff occluder, and every 30 s during 4 min of reperfusion. Pigs were instrumented with ultrasonic microcrystals measuring wall thickness in the anterior walls (left anterior descending artery territory) and lateral walls (left circumflex or right coronary artery territory) of both ventricles, and a left ventricular pressure microtransducer. RESULTS: During control and reperfusion, both anterior walls displayed similar systolic thickening. During coronary occlusion, the left ventricular anterior wall showed paradoxical systolic thinning (dyskinesia) whereas the right ventricular anterior wall showed only hypokinesia. CONCLUSIONS: In the presence of equal blood flow deprivation, the right ventricular anterior wall supplied by the left anterior descending coronary artery displays a significantly lesser degree of functional impairment than the left ventricular anterior wall supplied by the same artery. This differential effect may be due to mechanical unloading of the right ventricular anterior wall resulting from left ventricular anterior wall ischaemia. This afterload reduction due to decreased mechanical interaction between the two walls would allow the right ventricular anterior wall to express its contractile reserve in the form of systolic thickening. PMID- 1423416 TI - Cardioprotective effects of ischaemic preconditioning are not mediated by prostanoids. AB - OBJECTIVE: Some reports have suggested that the mechanism of ischaemic "preconditioning" is mediated through prostacyclins. In this study the hypothesis that the cardioprotective effect of preconditioning is due to the synthesis and release of prostaglandin/prostacyclin was tested by assessing whether aspirin, an inhibitor of cyclo-oxygenase, could block or prevent the protective effect of preconditioning. METHODS: In protocol I, three groups of rats were studied. (1) CONTROL: rats received 90 min of coronary occlusion followed by 4.5 h of reperfusion (n = 8). (2) Preconditioning: hearts were preconditioned by three repeated episodes of 3 min of coronary occlusion and 5 min of reperfusion, and then subjected to 90 min of occlusion followed by 4 h of reperfusion (n = 9). (3) Aspirin + preconditioning: aspirin (10 mg.kg-1) was given 10 min prior to the preconditioning. Rats then underwent preconditioning and occlusion/reperfusion as in group 2 (n = 8). In protocol II, two groups were studied. (1) CONTROL: rats received 90 min of occlusion and 4.5 h of reperfusion (n = 6). (2) Aspirin + single occlusion: aspirin (10 mg.kg-1) was given 10 min prior to the 90 min occlusion, and then rats underwent occlusion/reperfusion as in controls (n = 6). Female Sprague-Dawley rats weighing between 235-500 g were used. Planimetry was used to measure area at risk (AR) following blue dye injection and area of necrosis (AN) after tetrazolium staining. RESULTS: Protocol I: all three groups had comparable AR. AN/AR was reduced significantly (p less than 0.05) in both the preconditioning group [29.6(SEM 7.6)%] and the aspirin + preconditioning group [29.6(8.7)%] compared with the control group [59.3(3.4)%]. The incidence of ventricular tachycardia and/or fibrillation was also reduced in both the preconditioning and the aspirin + preconditioning groups. Protocol II: the area at risk, area of necrosis, and the indicence of ventricular arrhythmia were not significantly different between aspirin + 90 min occlusion and control groups. CONCLUSIONS: Preconditioning both with and without aspirin significantly reduced infarct size and the incidence of ventricular tachycardia and/or fibrillation. As the effects of preconditioning were not prevented by aspirin, this suggests that the cardioprotective effects of preconditioning are not mediated by prostanoids in the rat model. PMID- 1423417 TI - Deleterious cardiac effects of captopril during acute myocardial ischaemia in the dog. AB - OBJECTIVE: The aim was to evaluate the effects of the angiotensin converting enzyme inhibitor captopril on acute myocardial ischaemia. METHODS: Seventeen anaesthetised open chest dogs were randomised to 3 minute angioplasty balloon occlusions of the left circumflex coronary artery before and after intravenous infusion of captopril (n = 8) or placebo (n = 9). RESULTS: There was apparent worsening of ischaemia during balloon inflation after captopril infusion, when compared with control inflation, as suggested by further ST segment elevation of 1.8 (SD 1.8) mm, p less than 0.03, and by further lowering of regional myocardial pH [-0.05(0.05), p = 0.06], and peak positive and peak negative dP/dt [ 439(337)mm Hg.s-1, p less than 0.008; -470(316) mm Hg.s-1, p less than 0.004, respectively]. The increase in ischaemia occurred despite reduced double product after captopril administration. Regional myocardial blood flow in the ischaemic artery distribution was lower during post captopril balloon occlusion [-0.1(0.06) ml.min-1.g-1, p less than 0.005] than during control balloon inflation, while coronary vascular resistance increased by 161(172)% (range 45 to 497%, p less than 0.04). There were no significant differences in ST segments, pH, haemodynamic variables, or blood flow during balloon inflations before and after saline infusion. CONCLUSIONS: Despite lower myocardial metabolic demands, acute intravenous administration of captopril was associated with increased ischaemia during transient coronary artery occlusion. PMID- 1423418 TI - Local activation variability during monomorphic ventricular tachycardia in the dog. AB - OBJECTIVE: The aim was to determine the beat to beat variability in local activation time during sustained monomorphic ventricular tachycardia in a canine model of experimental myocardial infarction. METHODS: A digital template matching algorithm was developed for detecting subtle beat to beat variability in local activation timing at each of multiple ventricular sites. Ten electrically induced sustained ventricular tachycardia episodes, mean cycle length 211 (SD 40) ms, were endocardially and epicardially mapped in mongrel dogs weighing 15-20 kg. Digitised data were analysed for beat to beat local activation time variability. Similar data recorded during ventricular pacing at comparable rates and during sinus rhythm served as controls. RESULTS: The overall mean variability of local activation time for all 10 ventricular tachycardias was 3.2(1.6) ms, range 1.8(1.1) ms to 4.7(2.8) ms, in contrast to the overall mean variability of 0.2(0.4) ms (p = 0.0001) for ventricular pacing and 0.7(0.6) ms (p = 0.0001) for sinus rhythm. Oscillations in local activation time manifested alternans type periodicity during seven of 10 ventricular tachycardias independent of any alternans in local electrogram morphology. CONCLUSIONS: During sustained, monomorphic ventricular tachycardia, beat to beat variability and alternans type oscillations in local activation time are common and may be an intrinsic property of re-entry since they are negligibly small during ventricular pacing. PMID- 1423419 TI - Role of anisotropy in determining the selective action of antiarrhythmics in atrial flutter in the dog. AB - OBJECTIVE: The aim was to clarify the electrophysiological and anatomical features of the preferential site of action of antiarrhythmic drugs in the re entrant circuit of canine atrial flutter. METHODS: Electrophysiological and anatomical findings were correlated in 17 anaesthetised adult mongrel dogs with atrial flutter associated with an intercaval anatomical obstacle, before and after intravenous administration of disopyramide (2 mg.kg-1) and flecainide (2 mg.kg-1). RESULTS: Before drug injection, a rate dependent prolongation of conduction time occurred in the low right atrium where the conduction was slow during atrial flutter. Disopyramide (n = 8 dogs) and flecainide (n = 9 dogs) terminated atrial flutter, with conduction block occurring in this slow conduction area in the low right atrium. Although the degree of drug induced prolongation of refractoriness in this particular area was similar to those in other areas of the right atrium, conduction was depressed to a greater extent in this region. Anatomical study revealed that a thick pectinate muscle that branched from the crista or crista terminalis itself ran perpendicular to the wavefront of the pacing impulse and atrial flutter in this slow conduction area. CONCLUSIONS: These data indicated that slow conduction might be attributed, at least in part, to anisotropic conduction over the thick muscle bundle in the low right atrium, and that antiarrhythmic drugs preferentially produced conduction block in this area. Anisotropic conduction in the low right arium is an anatomical substrate for slow conduction in the re-entrant circuit and for the site preference of antiarrhythmic drugs in the present canine model. PMID- 1423420 TI - Effects of regional ischaemia, with or without reperfusion, on endothelium dependent coronary relaxation in the dog. AB - OBJECTIVE: The aim was to establish whether the duration of coronary ischaemia and coronary ischaemia with reperfusion selectively reduced the magnitude of relaxation mediated by endothelium dependent relaxing factor (EDRF) in response to thrombin, compared with relaxation produced by acetylcholine and calcimycin. METHODS: Adult male dogs, anaesthetised with sodium pentobarbitone (30 mg.kg-1 intravenously) were used. Coronary artery occlusions were maintained for either 15 or 45 min; in half the dogs from each timepoint, occlusion was followed by 60 min reperfusion. At the end of each in situ period, coronary arteries were removed from both ischaemic and non-ischaemic regions, cut into rings, and hung in isolated organ baths. Dose-response relationships to the EDRF dependent vasodilators thrombin, acetylcholine, and calcimycin, and to the EDRF independent vasodilator isoprenaline, were then established. RESULTS: Thrombin (0.003-0.3 units.ml-1) caused dose dependent relaxation in all tissues. Relaxant responses (E(max)) in the non-ischaemic vessels from both 15 and 45 min treatment groups were used as control data for the responses in ischaemic vessels. Maximum responses were not different in the non-ischaemic groups from either 15 or 45 min studies, at 82.7 (SEM 3.7)% after 15 min, and 82.1(2.4)% after 45 min. There was a small but significant reduction in E(max) after 15 min and 45 min ischaemia, to 74.4(3.2)% and 74.4(3.0)% respectively. Sixty minutes reperfusion provoked a further reduction in E(max) to 64.9(3.8)% after 45 min ischaemia, but not after 15 min ischaemia [70.3(4.2)%]. Neither 15 nor 45 min interventions altered E(max) of relaxation to acetylcholine or calcimycin (greater than 88.0% in each group). Similarly there were no significant differences between groups to the relaxation stimulated by isoprenaline (E(max) greater than 90.0%). CONCLUSIONS: The data suggest that loss of EDRF dependent relaxation to thrombin is more sensitive to ischaemia than the relaxation produced by either acetylcholine or calcimycin, and appears to be manifested early in the onset of ischaemic injury. PMID- 1423421 TI - Nitric oxide does not mediate flow induced endothelium dependent arterial dilatation in the cat. AB - OBJECTIVE: The aim was to determine whether the endothelium derived nitric oxide formed from L-arginine is the factor which mediates flow induced dilatation of conduit arteries. METHODS: Changes in diameter of feline femoral artery caused by blood flow rate increases, acetylcholine, and ATP were recorded during perfusion with blood in situ before and after the inhibition of endothelium derived nitric oxide synthesis by NG-nitro-L-arginine methyl ester and NG-monomethyl-L-arginine. Fourteen anaesthetised cats of either sex, weight 2.6-3.9 kg, were used for the studies. RESULTS: Intravenous administration of NG-nitro-L-arginine methyl ester and NG-monoethyl-L-arginine in doses 10 and 30 mg.kg-1 evoked a rise in mean systemic arterial pressure, constriction of the femoral artery, and considerable decrease in acetylcholine and ATP induced dilatation. However, it did not affect the dilator response induced by increased blood flow rate. CONCLUSIONS: Flow induced endothelium dependent arterial dilatation is not mediated by nitric oxide or, if nitric oxide is still released in response to flow rate increase, it has a source distinct from L-arginine. PMID- 1423422 TI - Decreased hypothalamic and medullary GABA turnover in spontaneously hypertensive rats. AB - OBJECTIVE: The aim was to assess whether Gamma-aminobutyric acid (GABA) neurone activities in the central nervous system, especially in the hypothalamus and medulla oblangata, are altered in hypertension. METHODS: Central GABA content and turnover rate were measured in spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY). GABA content was determined with high performance liquid chromatography, and in vivo GABA turnover rates were estimated by GABA accumulation after injection of amino-oxyacetic acid, a selective inhibitor of GABA degrading system. Two groups of nine week old male rats (32 SHR and 32 WKY) were used. RESULTS: GABA concentrations in cerebrospinal fluid were lower in SHR than in WKY. Since hypothalamus and medulla oblongata are the possible active sites of this system, basal GABA contents and in vivo GABA turnover rates were measured in hypothalamus and medulla oblongata. Basal GABA content in the medulla oblongata and hypothalamus was almost equal in SHR and WKY. On the other hand, GABA turnover rates were significantly lower in SHR than in WKY in both the hypothalamus and the medulla. CONCLUSIONS: Since it is known that GABA is an inhibitory neurotransmitter in the central nervous system and that it controls autonomic and cardiovascular activities, the findings suggest that the decreased hypothalamic and medullary GABAergic activities may permit sympathetic hyperactivity to contribute to the increase in blood pressure in SHR. PMID- 1423423 TI - Aortic input impedence and neurohormonal activation in patients with mild to moderate chronic congestive heart failure. AB - OBJECTIVE: The aim was to investigate the interrelation between pulsatile components (assessed by determination of aortic input impedance) and neurohormonal activation in chronic congestive heart failure. METHODS: Aortic input impedance, plasma noradrenaline, renin, atrial natriuretic factor, and arginine vasopressin were measured in 20 patients with mild to moderate chronic congestive heart failure (coronary artery disease n = 12, idiopathic dilated cardiomyopathy n = 8). RESULTS: Cardiac index [2.2(SEM 0.3) litre.min-1.m-2] and left ventricular ejection fraction [38(4)%] were reduced, and pulmonary wedge pressure was increased [21(2) mmHg]. Plasma concentrations of noradrenaline [462(62) pg.ml-1], renin [12(4) ng AI.ml.h-1], atrial natriuretic factor [408(64) pg.ml-1], and--to a slight degree--arginine vasopressin [1.1(0.3) pg.ml-1] were increased. Characteristic impedance Zc [80(6) dyne.s.cm-5) and relative oscillatory aortic input pressure power [10(1)%]--both reflecting the pulsatile components of left ventricular afterload--were within the normal range. There was no significant correlation between these variables and the degree of neurohormonal activation (r values: -0.05 to -0.35). CONCLUSIONS: The data show that in patients with mild to moderate chronic congestive heart failure there is no interrelationship between the degree of neurohormonal activation and pulsatile components of left ventricular afterload. This may indicate that in these stages of heart failure there are no trophic effects of stimulated neurohormonal systems on the physical properties of the great arteries. PMID- 1423424 TI - Compensatory subendocardial hyperkinesis in the cat is abolished during coronary insufficiency outside an acutely ischaemic region. AB - OBJECTIVE: The aims were to determine (1) whether acute coronary occlusion provoked uniform hyperkinesis in remote non-ischaemic myocardium, and (2) how subsequent coronary stenosis affected such hyperkinesis. METHODS: Two pairs of ultrasonic crystals were placed in the anterior left ventricular midwall of nine pentobarbitone anaesthetised open chest cats. One pair (longitudinal) ran parallel to subendocardial fibres; the other pair (circumferential) was aligned with subepicardial and mid-myocardial fibres. Following circumflex coronary occlusion, subsequent hypoperfusion of the anterior wall was established by controlled constriction of a shunt line from the right subclavian artery to the left main coronary artery in two discrete steps. RESULTS: Following circumflex occlusion maximum systolic shortening of segments aligned to subendocardial fibres increased from 6.7(SEM 0.9)% to 11.5(1.4)% (p less than 0.001), whereas circumferential segment shortening was unchanged, at 12.2(0.8)% v 14.1(1.1)%. During mild shunt stenosis [delta P = 42(2) mm Hg] subendocardial tissue blood flow in the anterior wall decreased by 42(10)% (p less than 0.001), and longitudinal segment shortening decreased from 11.5(1.4)% to 6.9(1.1)% (p less than 0.001). Corresponding shortening of circumferential segments did not change. During severe shunt stenosis [delta P = 52(3) mm Hg] subendocardial tissue blood flow decreased further, and shortening of longitudinal segments approached zero value (p less than 0.001). CONCLUSIONS: Compensatory hyperkinesis of remote non ischaemic myocardium following an acute coronary occlusion may depend mostly on augmented subendocardial contraction. PMID- 1423425 TI - Dispersion of coronary artery thrombi by antagonism of platelet serotonin receptor in the dog. AB - OBJECTIVE: Blockade of platelet 5HT2 receptors prevents coronary artery thrombi. This study explores the dispersal of established thrombus by such 5HT2 antagonism. METHODS: Seven open chest anaesthetised beagles were used in a repeated measures study of the action of MDL 11,939 to remove the participation of platelet 5HT2 receptors in the natural history of intracoronary thrombosis with cyclic blood flow reduction. Endothelial damage and critical diameter constrictors were applied to the circumflex coronary artery, and systemic blood pressure and circumflex blood flow were measured continuously. RESULTS: Cyclic flow reductions, which were established by build up and embolisation of platelet thrombi, were completely abolished by the 5HT2 antagonist MDL 11,939. The dose given in the first two experiments was 0.5 mg.kg-1, reduced to 0.2 mg.kg-1 for the third. Subsequent animals received 0.1 mg.kg-1. Mean blood pressure rose slightly. Adrenaline infusion at 0.4 micrograms.kg-1.min-1 failed to restore cyclic flow reductions in any animal and caused a small flow increase without affecting mean blood pressure. The pattern of blood flow restitution after administration of MDL 11,939 was of great interest. In all the animals flow spontaneously increased in a stepwise fashion (a double step in five dogs). The step up was markedly different from the increase in flow seen during adrenaline infusion. CONCLUSIONS: (1) These results are further evidence of the importance of serotonin as a mediator of platelet thrombus in stenosed coronary arteries. (2) The apparent dissipation of thrombi by MDL 11,939 may be of importance. PMID- 1423426 TI - Engineering and physiological approaches to the study of cardiovascular function. PMID- 1423427 TI - Engineering and physiological approaches to the study of cardiovascular function. PMID- 1423428 TI - The oxygen free radical system: from equations through membrane-protein interactions to cardiovascular injury and protection. AB - Highly toxic oxygen radicals and their metabolites have been implicated in the pathogenesis of ischaemia/reperfusion injury. These reactive oxygen species include the superoxide anion, hydrogen peroxide, hydroxyl radical, and singlet oxygen. The central theme of this review is first to discuss the basic mechanisms of free radical generation from various potential sources, to point out and emphasise the growing importance of the role of singlet oxygen, and then to discuss in depth membrane-protein interactions that ultimately lead to myocardial damage and dysfunction. With this background, we highlight several novel therapeutic strategies aimed at interrupting the oxygen free radical mediated component of ischaemia/reperfusion injury. It is hoped that this thesis will then serve as a future impetus to challenge these hypotheses and further build on this truly unique system that has assumed such an important role in the pathophysiology of myocardial ischaemia/reperfusion and inflammation. "To those of us who are humbly exploring the mysteries of science, we must project our findings and model our systems. For if correct, we have made a small contribution and, if wrong, we have forced others to eventually think." A V Hill, on the occasion of the 50th anniversary of E H Starling's Linacre lecture (University College, London, 1968). PMID- 1423429 TI - Reperfusion injury: laboratory phenomenon or clinical reality? PMID- 1423430 TI - The L type calcium current in single hypertrophied cardiomyocytes isolated from the right ventricle of ferret heart. AB - OBJECTIVE: The aim was to study L type calcium current alterations in relation to the action potential lengthening induced by hypertrophy in isolated cardiomyocytes from the right ventricle of ferret. METHODS: Chronic pulmonary artery constriction was established in adult male ferrets under anaesthesia. Sham operated animals were used as controls. Four to six weeks later the heart was excised and treated with a mixed collagenase-elastase solution to isolate the right ventricular myocytes. The calcium current was investigated in control and hypertrophied cells with the whole cell configuration of the patch clamp technique. The validity of the model was tested by analysis of the structural and passive electrical characteristics of the cells, which were enzymatically isolated from right ventricles previously overloaded (4 to 6 weeks) by clipping the pulmonary artery. RESULTS: Isolated cells from right ventricles submitted to a chronic pressure overload had well preserved cellular integrity suggesting the absence of myocardial failure. This compensated form of hypertrophy was characterised by a dilated transverse tubular system, which could explain the increased membrane capacity. Such cells developed a prolonged action potential with a less pronounced fast repolarisation phase inducing a higher plateau phase. When studied in physiological Tyrode solution the density and kinetics of the L type calcium current were not apparently modified, but a significant decrease in density was unmasked when sodium and potassium currents were suppressed by external and internal substitution of sodium and potassium by tetraethyl ammonium. CONCLUSIONS: The decrease in L type calcium current cannot be involved in the lengthening of action potential observed on hypertrophied myocytes, but it could account for the depressed contractile activity. A noticeable decrease of the transient outward current is suggested to explain the action potential alterations. PMID- 1423431 TI - Reactive and reparative myocardial fibrosis in arterial hypertension in the rat. AB - OBJECTIVE: Myocardial fibrosis is an important determinant of pathological hypertrophy. In two experimental models of arterial hypertension the purpose of the study was (a) to determine total collagen volume fraction and relative contribution of scarring and perivascular/interstitial fibrosis; and (b) to assess the effects of the aldosterone receptor antagonist spironolactone on these patterns of fibrosis. METHODS: 76 eight week old Sprague-Dawley rats weighing 180 to 200 g were used for the studies. Using videodensitometry total collagen volume fraction was separated into the various components for the left and right ventricles in the following experimental models: renovascular hypertension occurring following unilateral renal ischaemia; continuous aldosterone administration via osmotic minipumps with either high (AL) or low (ALLO) sodium diet; renovascular hypertension and AL after pretreatment and continuous treatment with either 20 or 200 mg.kg-1.d-1 subcutaneously of the competitive aldosterone receptor antagonist spironolactone. All groups were compared to age and sex matched controls. RESULTS: After eight weeks, systolic pressure was comparably increased in renovascular hypertension and AL and it remained raised with low dose spironolactone treatment in either model, but was normal with high dose spironolactone or low sodium diet. Left ventricular hypertrophy, expressed as a significant increase in left to right ventricular weight and left ventricle to body weight ratios, was present in renovascular hypertension, AL, and AL + low dose spironolactone compared to control (p < 0.005). In either ventricle: (1) the amount of interstitial/perivascular fibrosis and myocardial scarring was increased (p < 0.005) in renovascular hypertension and AL compared to control; (2) each was reduced (p < 0.005) with either dose of spironolactone; and (3) only scars were seen in ALLO. CONCLUSIONS: Myocardial fibrosis of either ventricle was comparable in renovascular hypertension and AL. Spironolactone was able largely to prevent the perivascular/interstitial fibrosis and scarring in either model irrespective of the development of left ventricular hypertrophy and arterial hypertension. Low sodium diet in hyperaldosteronism prevented hypertension and left ventricular hypertrophy, but not scarring. These findings suggest that a rise in plasma aldosterone, relative to sodium intake, may play a role in mediating collagen accumulation in the heart during the development of experimental arterial hypertension. PMID- 1423432 TI - Effect of transmural vagal stimulation on electrotonic current spread in the rabbit sinoatrial node. AB - OBJECTIVE: The effect of vagal stimulation on the decay of electrotonic potential caused by intracellular current injection and on input resistance was measured in the sinoatrial node of isolated rabbit right atria. METHODS: Studies were performed on New Zealand White rabbits weighing approximately 2-3 kg. Vagal stimulation was achieved by transmural stimulation of intramural nerve fibres in the presence of propranolol. A K+ perfused suction electrode was used to inject hyperpolarising current pulses; input resistance was measured by means of a double barrel microelectrode. RESULTS: Vagal stimulation which caused a 14-20% increase of cycle length diminished electronic potential significantly by a decrease of membrane resistance. The input resistance of the sinoatrial node was not affected. Space constant values calculated by using either a one or a two dimensional model of electrotonic current spread were decreased on average by 13% and 14% respectively. CONCLUSIONS: The results from this study show that vagal stimulation which gave rise to a moderate negative chronotropic effect and marked changes in action potential configuration of nodal fibres affects the electrotonic interaction within the sinoatrial node. This may have consequences for the electrical activity and synchronisation of the sinoatrial nodal fibres. PMID- 1423433 TI - Postischaemic metabolic and functional recovery of rat heart after transient reperfusion with various low Ca2+ concentrations. AB - OBJECTIVE: The effects of transient low Ca2+ reperfusion after ischaemia on metabolic and functional recovery were studied in isolated rat hearts. METHODS: 31P nuclear magnetic resonance (NMR) was used to monitor creatine phosphate, ATP, intracellular inorganic phosphate (Pi), and intracellular pH during control perfusion (15 min), total ischaemia (30 min), and reperfusion (30 min). During early reperfusion (0-10 min) perfusate [Ca2+] amounted to 1.3 (control group), 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, or 0.7 mmol.litre-1. During late reperfusion (10-30 min) perfusate [Ca2+] was 1.3 mmol.litre-1. Isolated rat hearts were used and perfused according to Langendorff. RESULTS: Recovery of creatine phosphate during early reperfusion was partly abolished during late reperfusion in the 0.1-0.4 mmol.litre-1 groups (p < 0.01). In the 0.1 mmol.litre-1 group creatine phosphate content after 30 min reperfusion was lower (p < 0.05) than in the control group. Recovery of ATP during early reperfusion in the 0.3 mmol.litre-1 group was better than in the control group (p < 0.01). After 30 min reperfusion ATP recovery was better in the 0.3 mmol.litre-1 group (p < 0.01) and worse in the 0.1 mmol.litre-1 group (p = 0.05) than in the control group. Decline of Pi during early reperfusion was more pronounced in the 0.2 and 0.3 mmol.litre-1 groups (p < 0.01) and in the 0.5 and 0.6 mmol.litre-1 groups (p < 0.05) than in the control group. In the 0.3 and 0.4 mmol.litre-1 groups, Pi after 30 min reperfusion was higher (p < 0.05) than after 10 min reperfusion. After 30 min reperfusion left ventricular developed pressure, measured with an intraventricular balloon, was lower in the 0.1 mmol.litre-1 group (p < 0.01) than in the control group. CONCLUSIONS: The data show that under the experimental conditions used successive postischaemic reperfusion with 0.1 and 1.3 mmol.litre-1 Ca2+ resulted in poorer metabolic and functional recovery of the hearts than continuous reperfusion with 1.3 mmol.litre 1 Ca2+. Postischaemic reperfusion with 0.1 mmol.litre-1 Ca2+ may predispose the heart to a mild calcium paradox. Successive reperfusion with 0.3 and 1.3 mmol.litre-1 Ca2+ was optimal in terms of ATP recovery but did not result in an increased recovery of left ventricular developed pressure. PMID- 1423434 TI - Impairment of endothelium dependent responses in a rat model of chronic heart failure: effects of an exercise training protocol. AB - OBJECTIVE: The aim was to document the response of aortic rings from a rat model of heart failure to endothelium dependent and endothelium independent vasodilating agents. The effects of an exercise training schedule upon these responses was studied. METHODS: Heart failure was produced in one group of female Wistar rats by coronary artery occlusion, and sham operations were performed in a matched group. The rats were allowed to recover for six weeks, following which half the rats with heart failure were started on a treadmill exercise schedule for a further six weeks. After this time the rats were killed, and rings of aorta were studied in an organ bath to measure the response to both endothelium dependent and endothelium independent vasoactive agents. RESULTS: The presence of heart failure was confirmed in both the non-trained (NT, n = 5) and trained rats (TR, n = 5), but not in the sham operated animals (SH, n = 6). The constrictor response to prostaglandin F2 alpha was similar in aortic rings from all the animals. The relaxation response to the endothelium dependent vasodilator acetylcholine (10(-7) and 10(-6) M) was impaired in the rats with heart failure compared to the sham operated animals (10% v 33% with 10(-7) M acetylcholine, p < 0.005). The dilator response in the trained rats was not significantly greater than in the non-trained rats (TR 35% v NT 24% with 10(-6) M acetylcholine). There was no difference in the response to sodium nitroprusside (10(-7) and 10(-6) M) between the three groups. CONCLUSIONS: Chronic heart failure impairs the response of aortic rings to the endothelium dependent vasodilator acetylcholine in a rat model of heart failure. The response to sodium nitroprusside, an endothelium independent relaxing agent, is not impaired by heart failure. These findings may help to explain the raised systemic vascular resistance and the failure of vasodilatation in skeletal muscle vasculature which limits exercise capacity in subjects with heart failure. PMID- 1423435 TI - Spontaneous arrhythmias in various models of cardiac hypertrophy and senescence of rats. A Holter monitoring study. AB - OBJECTIVE: The aim was to define experimental models of spontaneous arrhythmias in various models of cardiac hypertrophy in rats. METHODS: Cardiac hypertrophy was induced by several methods and 24 h Holter monitoring was recorded in conscious rats to quantify spontaneous arrhythmias in hypertrophied hearts. Male Wistar rats were studied. A group of young controls 1-2 months old (n = 16) was compared to four groups of animals with cardiac hypertrophy: (1) thyrotoxic rats which received a daily intraperitoneal injection of L-thyroxine for 7 d (n = 6); (2) rats subjected to abdominal suprarenal aortic stenosis (n = 11); (3) senescent rats 22-24 month old (n = 6); and (4) S-DOCA-salt (senescent animals rendered hypertensive by uninephrectomy and DOCA-salt treatment, n = 8). RESULTS: (1) Thyroxine resulted in 20% cardiac hypertrophy, with normal arterial tension, sinus tachycardia, a shorter P wave length and PR interval, and frequent (5/6) atrioventricular block. No premature beats were seen. (2) In aortic stenosis, atria and left ventricle were hypertrophied by 53% and systolic carotid pressure increased by 63%. The incidence of supraventricular premature beats was increased [frequency = 0.70 (SEM 0.3) per 24 h in control v 99(61) in aortic stenosis, p < 0.05]. Ventricular premature beats remained as rare as in control. (3) In senescent and S-DOCA-salt rats all types of spontaneous arrhythmias, but specially supraventricular arrhythmias and atrioventricular block, were frequent. Cardiac hypertrophy produced by DOCA-salt treatment in senescent rats had no effect on the incidence and nature of arrhythmias, but resulted in an increased QTc interval. CONCLUSIONS: Senescent rats and rats with aortic stenosis represent valid models of spontaneous arrhythmias occurring in the absence of ischaemia or toxic insult. Spontaneous arrhythmias in rats are mainly of supraventricular origin. Hyperthyroidism in rats is a model of atrioventricular block probably related to tachycardia. Holter monitoring in rats may have several potential pathophysiological and pharmacological applications. PMID- 1423436 TI - Cumene hydroperoxide induced changes in calcium homeostasis in cultured neonatal rat heart cells. AB - OBJECTIVE: The relationship between oxidative stress induced cell necrosis and perturbation of intracellular calcium homeostasis was investigated in cultured myocytes. METHODS: Cultured neonatal rat heart cells were loaded with fura-2 AM to measure cytosolic free calcium ([Ca2+]i). Probenecid, an inhibitor of organic anion transport, was present during the experiment to reduce efflux of fura-2 from the cytoplasm. Cells were exposed to cumene hydroperoxide, a toxic organic hydroperoxide that is known to induce oxidative stress in myocytes. The efficacy of the protective agents Trolox C (a vitamin E analogue) and chlorpromazine (a phospholipase inhibitor) on cumene hydroperoxide induced cell injury was determined. RESULTS: [Ca2+]i in control cells was constant (60 nM) during an incubation time of 45 min. Probenecid did not affect [Ca2+]i levels or cell viability under the experimental conditions. Cumene hydroperoxide caused a sustained rise in [Ca2+]i starting after 5-10 min, to a level of 1300 nM at 45 min. After 20-25 min the viability of the heart cells started to decline and after 45 min 44% of the cells were irreversibly injured. The loss of cell viability was expressed as percentage decrease of the fluorescence at 360 nm (the calcium independent wavelength), since the percent release of cellular alpha hydroxybutyrate dehydrogenase (alpha-HBDH) activity equalled the percent decrease of the fluorescence at 360 nm. Trolox C and chlorpromazine almost completely prevented the cumene hydroperoxide induced alpha-HBDH release. The [Ca2+]i of myocytes incubated with cumene hydroperoxide in combination with Trolox C rose to 1000 nM without affecting cell viability. The cumene hydroperoxide induced rise in [Ca2+]i was markedly reduced by chlorpromazine (at t = 45 min, [Ca2+]i = 360 nM). Addition of Trolox C to untreated cells did not influence [Ca2+]i, whereas chlorpromazine alone induced a slight increase of [Ca2+]i up to 360 nM with complete preservation of cell viability. CONCLUSIONS: Trolox C and chlorpromazine are very effective inhibitors of cumene hydroperoxide induced perturbation of calcium homeostasis and subsequent cell death. A role for peroxidation of membrane phospholipids and activation of calcium dependent phospholipase in the cascade of events leading to irreversible injury is suggested. PMID- 1423437 TI - Neural regulation of heart rate variability in endurance athletes and sedentary controls. AB - OBJECTIVE: The aim was to examine the cardiac autonomic responses to orthostatic stress and recovery from steady state exercise in endurance trained athletes and sedentary subjects. METHODS: The power spectrum of heart rate variability was measured before and after exercise in 10 male long distance runners and 14 male sedentary control subjects. Both groups were comparable in sex, age, and body mass index. Continuous ECG recordings were obtained during the following physiological manoeuvres: 45 min supine rest state; 10 min standing; 15 min steady state exercise at 50% maximum workload, and 15 min while supine during post-exercise recovery. The resting heart rate of athletes was lower than controls, at 52(SD 4.9) v 67(8.7) beats.min-1, p < 0.001. Power spectrum analysis was performed using autoregressive modelling. RESULTS: The resting high frequency (HF) vagal component was higher in athletes than controls, at 62 (10.7) v 44(22.4) beats.min-1.Hz-1, p < 0.05. The resting low frequency (LF) peak power was significantly reduced in athletes, at 54(9.9) v 70(19.5) in control, p < 0.05. Although no group differences were observed during upright posture or exercise, the LF:HF area ratio had already returned to pre-exercise levels within 5 min of recovery in athletes. Conversely, it required up to 15 min of recovery before a noticeable decrease in the LF:HF area ratio was seen in controls. CONCLUSIONS: These data support the hypothesis that endurance training modifies heart rate control in whole or in part through neurocardiac mechanisms. PMID- 1423438 TI - Comparison of laser fluorescence and longitudinal microradiography for quantitative assessment of in vitro enamel caries. AB - A new quantitative, non-destructive method using laser-induced fluorescence (LAF) was compared with longitudinal microradiography (LMR) for assessment of mineral changes in enamel slices using an in vitro caries model. Ten enamel slices, cut longitudinally from sound natural smooth surfaces of human teeth, were exposed to de- and remineralization in a pH-cycling model. The enamel slices were subjected to LAF and LMR measurements before and at 2, 4, 7, and 9 days of demineralization. For LAF, the average fluorescence radiance decreased during the demineralization period with 11% by day 2 and 49% by day 9. For LMR, the corresponding average loss of mineral content changed with 0.01 and 0.10 kg.m-2 over the same time period. The mineral losses in each individual enamel slice measured with the two techniques were strongly correlated, r = 0.97. The Spearman rank correlation coefficient for all LAF and LMR demineralization results was 0.86. The precision (coefficient of variation) for LAF was 3.1%, corresponding to 0.005 kg.m-2, and the repeatability error for LMR was 0.02 kg.m-2, indicating a lower discrimination threshold for LAF compared to LMR. It was concluded that the new, sensitive, non-destructive LAF method provides possibilities for further improvement in the quantification of initial caries lesions in natural smooth enamel surfaces for use in in vitro studies. Furthermore, it offers potential in in situ caries studies as well as a tool in the diagnosis of early enamel caries in vivo. PMID- 1423439 TI - High resolution fluoride profiles of artificial in vitro lesions treated with fluoride dentifrices and mouthrinses during pH cycling conditions. AB - A pH cycling model which incorporated a severe demineralization component was used to evaluate fluoride uptake and lesion progression for each of a NaF-based dentifrice, NaF-based mouthrinse and a monofluorophosphate (MFP)-based dentifrice. Simultaneous transverse fluoride and calcium profiles across the resulting artificial lesions were obtained using a proton microprobe technique with a resolution of approximately 10 microns. Longitudinal microhardness testing and proton microprobe calcium profiles were used to determine the extent of lesion progression (delta Z) with respect to untreated controls. Under the pH cycling conditions of the present study, the NaF dentifrice and mouthwash were observed to have a considerably higher uptake of fluoride in the lesion than the MFP dentifrice. Although the mineral content profiles of the lesions differed for treatments with each of the fluoride products, the differences were not significantly different in this model. PMID- 1423440 TI - Fluoride and calcium content of enamel organ, muscle, liver and plasma in rats. AB - Nine-day-old rats were given oral fluoride doses (0.5 micrograms F/g body weight). Plasma, enamel organ, muscle and liver samples were collected from nondosed pups (baseline) and 15, 30, 60 and 120 min after the dose. Samples were assayed for fluoride and calcium concentrations. Adult rats were given 20 ppm F water for 6 weeks, and the same tissues were sampled and assayed for fluoride concentrations only. In the first phase of the study, enamel organ had significantly higher fluoride and calcium content than liver and muscle. In adult rats the fluoride content of enamel organ was again significantly higher than for liver and muscle. PMID- 1423441 TI - Effect of slow-release chlorhexidine mouthguards on the levels of selected salivary bacteria. AB - This study evaluated the effect of an alternate delivery system for chlorhexidine on salivary levels of mutans streptococci (MS) and other selected oral bacteria. On the basis of salivary MS levels > or = 10(4) CFU/ml, 22 subjects were enrolled. All caries lesions were restored prior to treatment. Two pretreatment paraffin-stimulated saliva samples were obtained for culturing at least 1 week apart. Complete-arch vacuum-adapted mouthguards were individually fabricated and coated internally with a 3% w/v chlorhexidine varnish. Mouthguards were worn for an average of 7 h/night for 7 nights. Saliva samples were obtained immediately after treatment and 1 and 3 months later. There was no significant change in levels of any of the monitored bacteria between the two pretreatment samples. A significant and specific reduction in salivary MS levels was observed in the three after-treatment samples as compared with baseline values (p < 0.001, p < 0.001, p < 0.05, respectively). The levels of Actinomyces viscosus were also measured, and there was a significant reduction immediately after treatment (p < 0.05), a return to baseline values at 1 month, and a significant increase above baseline values at 3 months, (p < 0.001). There was no significant change in saliva volume, in total numbers of facultatively anaerobic bacteria, or in levels of lactobacilli or Streptococcus sanguis. This treatment system is capable of significant and specific suppression of MS levels for up to 3 months without retreatment. PMID- 1423442 TI - Effects of chlorhexidine-fluoride gel treatments in mothers on the establishment of mutans streptococci in primary teeth and the development of dental caries in children. AB - In a longitudinal 3-year study, 151 children were followed for the colonization of the primary dentition by mutans streptococci (MS) and for the development of dental caries. At the age of 1 year, the child-mother pairs were divided into three groups on the basis of the levels of MS in maternal saliva. In the experimental group, the mothers had MS levels higher than 10(5) CFU/ml, and they were given chlorhexidine (1%)-sodium fluoride (0.2%) gel treatments twice a year for 3 years. Two control groups were formed. In control group 1, the mothers also had high levels of MS, but no gel was given. In control group 2, the mothers had low (< 10(5) CFU/ml) baseline levels of salivary MS, and no chlorhexidine fluoride gel was used. In the total study population, 16, 42, and 54% of the children were colonized by MS by the age of 2, 3, and 4 years, respectively. Most children harbored only Streptococcus mutans, but 2 had both S. mutans and Streptococcus sobrinus, and 2 had only S. sobrinus. Twenty-eight percent of the MS-positive children developed caries by the age of 4 years, whereas 4 out of 27 children with dental caries did not have any detectable MS in their plaque samples. Both the colonization by MS and the caries incidence were highest in control group 1 and lower in the experimental group and in control group 2. These observations suggest that the reduction of maternal salivary MS at the time of tooth emergence may delay, or perhaps even prevent, the colonization of MS in the children's primary dentition with a concomitant decline in caries incidence, even in a population with an already low prevalence of dental caries. PMID- 1423443 TI - Effect of delmopinol on the viscosity of extracellular glucans produced by Streptococcus mutans. AB - The surfactant delmopinol, which is a new antiplaque agent with a low anti microbial profile, was tested for its effects on the viscosity of bacterial extracellular glucans. Glucans were isolated from Streptococcus mutans broth supernatants incubated with 0.15 M sucrose in 50 mM sodium phosphate buffer at pH 6. The viscosity was measured in a shear rate range from 15 to 230 reciprocal seconds. The viscosity of the water-soluble glucan was found to be independent of shear rate whereas the water-insoluble glucan showed a strong shear thinning. The addition of delmopinol to preformed glucans did not affect the viscosity nor the shear rate dependence of the glucans. However, when present during synthesis of the polysaccharides, delmopinol was found to reduce the viscosity of both water soluble and water-insoluble glucans by approximately 50% at the shear rates investigated. The reduction in viscosity for the water-soluble glucans was obtained at a delmopinol concentration of 0.32 mM (0.01%) and for the water insoluble glucans at 3.2 mM delmopinol. The observed reduction of viscosity of glucans indicates that the in vivo stability of plaque matrix after delmopinol treatment would be lowered, which may lead to a reduction of plaque cohesion and thus facilitate mechanical plaque removal. PMID- 1423444 TI - Effect of sugarcane chewing on plaque pH in rural Kenyan children. AB - In 5 rural Kenyan children, the effect of sugarcane chewing on plaque pH was compared with the effect of a mouthrinse with 10% sucrose at various intraoral sites. They all had poor oral hygiene and at least two carious cavities in occlusal surfaces of molars. pH measurements were conducted under field conditions using paladium touch microelectrodes connected to a battery-operated pH meter. There was a marked difference in pH response of non-carious approximal sites between maxilla and mandible, with the lowest values in the maxilla. However, the pH recovery following the instantaneous drop occurred in parallel even if most pH values had not returned to baseline values 30 min after the sucrose rinse. Following the sugarcane chewing, the pH fall was less pronounced on all sites, and within 5-10 min the values had returned to resting pH and even exceeded this. In carious cavities, a similar pattern was observed, although the acidity in these sites was more pronounced, also reflected in a lower resting mean pH. The main conclusion from this study is that sugarcane chewing yields a less pronounced pH drop and a quicker pH recovery in dental plaque than is seen following a mouthrinse with 10% sucrose. This difference probably results from stimulation of salivary flow associated with the chewing. PMID- 1423445 TI - Effect of hard cheese exposure, with and without fluoride prerinse, on the rehardening of softened human enamel. AB - The in situ rehardening effect was compared between Cheddar cheese consumption and saliva secretion with and without a fluoride pretreatment on softened human enamel. Ten volunteers wearing prostheses which held slices of human enamel participated in this study. Average microhardness of enamel was determined on the surface at baseline, after exposing to an acidic beverage, after exposing to saliva and mastication of cheese, with and without a mouth F prerinse (10 ml Meridol containing 0.025% F). The rehardening was increased in the groups consuming cheese compared to the saliva controls. The effect was increased by an F prerinse; the initial hardness of the intact enamel surface, however, was not reached. PMID- 1423446 TI - Effect of glutardialdehyde on secondary caries in situ. AB - In this paper the results are presented on the effect glutardialdehyde (GDA) on the in situ demineralization of human enamel and dentine around an artificial gap of 200 microns width. In this model secondary enamel and dentine caries is simulated in situ; the mineral loss was quantified. The results show that a 2-min application of a 2% acidic GDA solution reduces dentine demineralization substantially, but does not influence enamel demineralization. Microradiography showed a reduction of mineral loss values around the gap in dentine by about 30%. The beneficial effect of GDA on dentine is presumably a combined result of collagen fixation, the reduced diffusion of calcium and phosphate ions out of the dentine lesion, and antibacterial action. The results indicate that GDA might play a role in the future reduction or prevention of secondary dentine caries. PMID- 1423447 TI - Effect of oral care habits on caries in adolescents. AB - Data on toothbrushing habits were collected during a 3-year caries clinical trial of sodium monofluorophosphate toothpastes in Lanarkshire, Scotland, involving 3,005 schoolchildren of mean age 12.5 years at baseline. Stated normal brushing frequency and oral rinsing method after brushing were recorded. Half the panel indicated they rinsed their mouths after toothbrushing using a beaker. The proportion of the panel brushing once per day or more increased during the trial. Differences in oral habits were observed between the sexes, with 42% of girls and 52% of boys being non-beaker rinsers and 73% of girls, but only 44% of boys, brushing their teeth at least twice per day. Twice-a-day brushers had a consistently lower caries increment than less frequent brushers. This was also seen in the baseline prevalence data, but did not account for all incremental differences noted. Subjects using beakers had consistently higher increments than non-beaker rinsers. Again, this difference could not be explained by variations in baseline prevalence. Differences in the caries increment were also observed between boys and girls, these appearing to be linked both to the cumulative effect of male/female habit variations plus a difference in the baseline caries prevalence. A dose response to the three fluoride levels, i.e 1,000, 1,500, and 2,500 ppm F, was seen for the different habit combinations which again could not be explained by differences in the baseline caries prevalence. PMID- 1423448 TI - Clinically undetected occlusal dentine caries: a radiographic comparison. AB - The occlusal bite-wing radiograph evaluations of 131 14-year-old and of 123 17- and 20-year-old Dutch persons were compared with the clinically collected observations. The clinical observations and the bite-wing radiographs were collected as part of a longitudinal epidemiological survey conducted in 1987 and 1990. Comparison of the evaluations of the first and second molar teeth showed significantly more radiolucencies in all three age groups than expected clinically. Of the clinically judged 'sound' surfaces, 26% in the 14-, 37.5% in the 17- and 50% in the 20-year-old group showed a radiolucency on the bite-wing radiograph. In the 14-, 17- and 20-year-old age group a radiolucency was noticed on the bite-wing radiograph in 32, 44 and 58% of the sealed teeth, respectively. The radiolucencies below the occlusal enamel of sealed teeth were most likely due to the problems in diagnosing occlusal dentine lesions correctly with the clinical diagnostic methods. Therefore not only approximal but also occlusal bite wing radiograph judgement before sealant application seems to be advisable now. Because of the numbers of clinically undetected lesions it may be advisable to reconsider the criteria for occlusal diagnosis in epidemiological surveys and to judge not only the approximal but also the occlusal surfaces in epidemiological surveys when bite-wing radiographs are available. PMID- 1423449 TI - Class II amalgam restorations, glass-ionomer tunnel restorations, and caries development on adjacent tooth surfaces: a 3-year clinical study. AB - Eighteen caries-active adolescents, each having both a class II conventional amalgam (Dispersalloy) and a glass-ionomer (Ketac Silver) tunnel restoration of the same age placed on a contralateral tooth, were part of a 3-year clinical study. At the 1- and 2-year examinations all test restorations were assessed as acceptable in all patients. At the 3-year assessment three amalgam restorations failed due to recurrent caries, and one glass-ionomer restoration failed due to marginal ridge fracture. During the entire study period, the requirement of restorative therapy because of primary proximal caries was significantly reduced (p < 0.05) on tooth surfaces adjacent to the glass-ionomer restorations as compared with that on tooth surfaces adjacent to the amalgam restorations. PMID- 1423450 TI - Morphological characteristics of different types of neurons in the ventrooralis anterior, ventrooralis internus, and ventrooralis posterior nuclei in the human thalamus. AB - 1. Golgi-Kopsch preparations of the oral ventral nuclei of human thalamus were analyzed in an attempt to classify the neuronal types. 2. Three types of neurons are described for the first time in humans. Type I neurons are large or medium in size and bear dendrites with protrusions, spines, and short hair-like appendages. Some have a radiate dendritic arbor and others have dendrites grouped in tufts. The dendritic trees of these neurons are dense. 3. Type II neurons are medium or small in size with less dense dendritic trees. These cells have somatic as well as dendritic appendages of different forms. 4. Relatively rare is a type of very small neurons, type III, with few and sparsely branching dendrites. PMID- 1423451 TI - [Progression of chronic glomerulonephritis. Myths and facts]. AB - Chronic glomerulonephritis is still the most frequent cause of irreversible renal failure. The aetiology of the majority of glomerulonephritis is unknown but it seems that they are genetically determined. In their genesis immunological factors participate but in their development and progression non-immunological factors are also involved. The author presents a review of contemporary therapeutic possibilities. PMID- 1423452 TI - [Evaluation of glomerular filtration in patients after renal transplantation and treatment with cyclosporin A]. AB - According to some findings (Ross et al. 1987) the creatinine plasma concentration (Pcr) is an inaccurate indicator of glomerular filtration (GFR) in patients with a transplanted kidney, treated with cyclosporin A (CyA), who are in a stabilized state of renal function. In the submitted work the authors investigated whether the inaccuracy of the assessed GFR based on Pcr or creatinine clearance (Ccr) is greater than in patients with various chronic renal diseases who at the time of examination did not take any drugs. The investigation was made in 30 patients with a transplanted kidney treated with CyA as well as azathioprine and prednisone. The authors examined also 51 patients with various chronic renal diseases, mostly chronic glomerulonephritis or tubulo-interstitial nephritis. The GFR value was assessed on the basis of polyfructosan clearance (CPF). In subjects with a transplanted kidney a significant linear relationship was found between Ccr and CPF (r = 0.829, p < 0.001). A similar relationship was found in patients with chronic renal disease (r = 0.935, p < 0.001). The regression lines characterize this relationship in both groups and do not differ significantly. Between values of Pcr and CPF a significant relationship of a hyperbolic character was found in both groups (r = 0.693, p < 0.001 and r = 0.741, p < 0.001 resp.). The hyperbolic relations found in the examined groups did not differ significantly. The findings confirm that a normal or only slightly elevated Pcr value can be associated with a markedly reduced GFR, in some instances to as much as one third of the normal values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423453 TI - [Clinical study of biocompatibility of dialysis membranes made from non-modified and modified cellulose]. AB - Basic biocompatibility parameters of dialysis membranes made of non-substituted regenerated cellulose (NRC) and cellulose membranes with hydroxyl groups substituted, to a higher (H) or lower (L) degree, by dl-ethyl-amino-ethyl groups (DEAE), or by acetate (CA) were investigated in a 16-week clinical study, involving 10 long-term haemodialysis patients. In the 15th minute of dialysis, the decrease in blood leukocyte count, while using NRC (0.24 +/- 0.03 of baseline value, arithmetic mean +/- SEM) was deeper compared with that seen in DEAE-L (0.88 +/- 0.10, p < 0.001), in DEAE-H (0.79 +/- 0.10, p < 0.01), and in CA (0.73 +/- 0.05. p < 0.05). In the 15th minute of the procedure, C5a concentrations, reflecting complement activation, were higher in NRC (4.4 +/- 0.51 micrograms/L) than in DEAE-L (1.41 +/- 0.22, p < 0.001), in DEAE-H (1.68 +/- 0.47, p < 0.01), and in CA (1.68 +/- 0.22, p < 0.01). Activated clotting times were, in the 10th minute of the procedure, significantly longer in NRC (2.94 +/- 0.37 of baseline value) than in DEAE-H (1.74 +/- 0.10, p < 0.05) and, by the end of dialysis, the difference between these membranes (NRC: 1.47 +/- 0.21, DEAE-H: 0.85 +/- 0.08, p = 0.07) was close to the level of statistical significance. The authors conclude: 1. Substitution of the hydroxyl groups of regenerated cellulose reduces the decrease in leukocyte count and complement activation in the initial phase of haemodialysis. 2. At the same time, substitution by DEAE groups may raise thrombogenicity, as indicated by the shorter activated clotting times.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423454 TI - [Rapidly progressing glomerulonephritis with antibodies against cytoplasm of neutrophilic leukocytes]. AB - The authors describe the clinical, laboratory and morphological findings, the clinical course and response to treatment in three patients with rapidly progressing glomerulonephritis where positive antibodies against the cytoplasm of neutrophil granulocytes (ANCA) were found. The authors confront their own clinical experience with data in the literature. Examination of ANCA is not only a significant contribution towards a more accurate diagnosis of renal vasculitis, but also an indicator of the activity of the disease and thus of the effectiveness of immunosuppressive treatment. PMID- 1423455 TI - [14 years of the peritoneal dialysis program at the internal medicine department in Strahov (1978-1991)]. AB - The authors present an account of 14 years experience of the department as regards treatment of chronic renal failure by peritoneal dialysis. Initial experience revealed that this method is feasible as an alternative of haemodialyzation treatment even in case of limited technical possibilities (using the so-called bottle system) but treatment was associated with a high incidence of peritonitis. During the subsequent period the incidence of peritonitis was substantially reduced in conjunction with the elaboration of hygienic provisions, enlightment of patients and a change from the regime of continual exchanges in a home environment to a regime of intermittent peritoneal dialysis performed mostly in hospital. Experience assembled in the department was also important. The longest period of treatment is 60 months. In another 18 patients it is more than 20 months. The most frequent cause of termination is loss of the ultrafiltration capacity of the peritoneum. Several patients had successful transplantations. The prolonged experience can be used at present when the so-called bag system is introduced. PMID- 1423456 TI - [Interesting urinary findings in acute intermittent porphyria]. AB - The authors describe an uncommon case of a patient with acute intermittent porphyria whose urine on standing, when exposed to light and air, turned dark and eventually black. The reason was increased excretion of porphobilin. The urine continued moreover increased amounts of Thormahlen-positive substances, typical melanogens were not detected, however. The authors wish to draw attention to possible diagnostic errors which arise due to erroneous interpretation of laboratory results. PMID- 1423458 TI - [Infectious diseases--a threat to participants in "Operation Desert Storm"]. PMID- 1423457 TI - [An ecological theme in the play "Enemy of the people" by H. Ibsen]. PMID- 1423459 TI - [The need for medical science and research. I. The danger of provincialism]. PMID- 1423460 TI - [Present views on classification of cerebrovascular diseases]. AB - In conjunction with the declaration of the "brain decade" which was called for by the unfavourable position as regards early diagnosis and by inadequate treatment of cerebral diseases, the author reflects on the importance of classification of cerebrovascular diseases. He submits a historical review of different classifications of cerebrovascular diseases starting with the international classification of diseases introduced into practice as early in 1893, the clinical and research classification elaborated by Millikan in 1975--both are still used by WHO--to the most recent suggestions of Hachinski of 1990 and the Classification of spontaneous intracerebral haematoma by Mizukami elaborated in 1985. The paper contains also the author's own modification of the clinical and research classification. PMID- 1423461 TI - [The effect of isometric loading on diastolic left ventricular filling in healthy individuals studied by the Doppler technic]. AB - The authors examined by Doppler echocardiography 30 subjects aged 21-30 years, exposed during examination to an isometric load by using a manual balloon dynamometer. The authors investigated different indicators of left ventricular filling during diastole and their indexes which evaluate indirectly the left ventricular diastolic function. The assessed correlations of some indicators with the quantitative expression of the isometric load (double product) were as follows: peak speed E - r = 0.3671 (p < 0.05), peak speed A - r = 0.6098 (p < 0.001), index of rations of peak speeds E/A - r = 0.6098 (p < 0.0001, sum of speed--time integrals TVIE + TVIA - r = 0.6469 (p < 0.001) and the time of retardation of the early filling phase of the left ventricle related to the heart rate DCT/TF - r = 0.7249 (p < 0.001). A statistically significant increase during the load was recorded in the peak speed A and a reduction of the E/A ratio (p < 0.01). The time speed integral TVIE increased (p < 0.01), both indexes TVI E + A and TVI E/A declined (p < 0.05). The time of retardation of the early filling stage to the early filling time DCT/DFT increased (p < 0.05) and DCT in relation to the heart rate DCT/TF declined significantly (p < 0.01). There was an insignificant decline of the peak speed of early filling E and its time-speed integral, TVI E. The sum of time-speed integrals TVIE + A did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423462 TI - [The character of left ventricular filling measured by pulsed Doppler echocardiography in patients with various degrees of arterial hypertension]. AB - The authors assessed, using Doppler echocardiography under standard conditions, indicators of left ventricular filling in 95 patients, mean age 52 years, with arterial hypertension of varying severity. The patients were divided into four groups: Group I--Patients with severe hypertension and concentric hypertrophy of the left ventricle (LV). Group II--Patients with severe hypertension without organ changes. Group III--Patients with mild hypertension without organ changes. Group IV--Patients with severe hypertension, hypertrophy of the LV and signs of its failure grade II according to Killip's classification. The results were compared with findings in a group of 30 normal subjects of similar age. In all groups of patients statistically significant differences were found in the type of left ventricular filling, as compared with normal subjects. In less severe affection of left ventricular function, where impaired active relaxation of musculature predominates (groups I, II and III), the left ventricular filling during early diastole was reduced, slower and its main part was shifted to the late stage of diastole. The ratio of the late and early flow rate through the mitral orifice Av/Ev and the ration of time/rate integrals of these rates, TVIA/TVIE, were elevated, as compared with normal subjects, similarly as the time value of retardation of early diastolic flow through the mitral orifice corrected with regard to the heart rate, DT/TF. The value of maximal flow through the mitral orifice during early diastole, PFRB was reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423464 TI - [The status of children worldwide in 1991 through the eyes of the UNICEF/Children's Fund of the United Nations]. PMID- 1423463 TI - [Functional determination of C1-inhibitors in human blood]. AB - The author describes the method of assessment of the C1-inhibitor, the principle being activation of plasma prekallikrein by Hageman factor fragment (HFf) to the active enzyme kallikrein which splits the specific chromogenic substrate NO-Pro Phe-Arg-pNA. In the presence of acetone the influence of C1-INH is eliminated and the assessed amount of kallikrein corresponds to the prekallikrein plasma level. In a parallel estimation without acetone after formation of the C1-INH complex the residual amount of kallikrein is assessed. The difference between the two levels is proportional to the formed enzyme-inhibitor complex. The method was tested on plasma of healthy donors and the results were compared with assessment of C1-INH by a modification of Schapira's method (6) (correlation coefficient r = 0.88) and with Cullmann's method (8) (r = 0.61). The advantage of the proposed method is that it does not require commercially unavailable enzyme preparations, that it uses as activating agent HFf concentrate, prepared in the laboratory and that along with the C1-INH level also the plasma level of prekallikrein is assessed. PMID- 1423465 TI - [The J.E. Purkinje Czechoslovak Medical Society, its past, present and future]. PMID- 1423466 TI - [Present possibilities of use of intravascular ultrasound examinations]. AB - Catheter intravascular imaging is currently used as an adjunct to contrast angiography and angioscopy in peripheral and coronary arteries. At present the smallest catheters are 3.0 F (1.0 mm). Frequencies used are from 10 to 40 Mz, which allow high resolution imaging of structures close to the transducer. Mechanical and phased array systems are used, introduced either on the wire or through fine plastic catheter. More recent is the monorail system improving the flexibility and tracking of the mechanical systems. The review presents current status of catheters and diagnostic possibilities. Normal arteries have typical three layered appearance (intima, media, adventitia). Ultrasound can be reliably used to distinguish abnormal vascular segments. Atherosclerotic plaques can be subclassified on the basis of plaque composition. Thrombus is characterized by granular appearance with varying sonographic gray levels. Dissection and intimal flaps are also visualized by intravascular ultrasound. Potential utility of intravascular ultrasound in the assessment of endovascular interventions and its limitations are discussed. PMID- 1423467 TI - [Energy expenditures in patients with acute and chronic catabolic conditions]. AB - The authors investigated the energy expenditure and utilization of different nutrients by indirect calorimetry. They examined three groups of subjects: patients with acute febrile diarrhoeal diseases (n = 36), patients with subacute to chronic severe febrile diseases (n = 10) and healthy subjects (n = 21). The measurements were made three times a day. In all groups the energy requirements of the organism were met in the morning above all by fats, in the course of the day the ration of utilized carbohydrates increased markedly. The authors discuss the problem of optimal nutrition of patients in a critical condition from the quantitative and qualitative aspect. PMID- 1423468 TI - [Use of walking in the evaluation of aerobic fitness]. AB - The reliability and validity of assessment of the maximal oxygen consumption as a criterion of aerobic fitness by the 2000 m walking test was established in 38 students of the military secondary school (mean age 17.8 +/- 0.4 years). The reliability of the 2000 m walking test is very high, during repeated estimations in the course of one week we find a correlation coefficient of r = 0.82 (p < 0.001). There is also a close correlation of 2000 m walking time and 2000 m running time (r = 0.67, p < 0.001). A group of 18 students selected at random from the above group was examined in the laboratory on a treadmill up to vita maxima. A close correlation was found between the results during walking and the maximal oxygen consumption (VO2max.kg-1) (r = -0.59 and -0.60) and also the 2000 m running time and VO2max.kg-1 (r = 0.59), p < 0.01 in all instances. The standard error of the mean of the maximal oxygen consumption estimate from the 2000 m walk is 3.44 ml.kg-1 x min-1 (5.7%) and from the running time of the same distance 3.49 ml.kg-1 x min-1 (5.8%). These results justify the conclusion that the 2000 m rapid walking test (normal style) is a simple alternative way for estimating the maximal oxygen consumption and thus also for evaluating the level of aerobic fitness with an accuracy which matches that, when running is used for the test. PMID- 1423469 TI - [Initial experience with the treatment of endobronchial lesions using the Nd:YAG laser]. AB - Endobronchial treatment by means of a laser acquired during the past ten years a firm place in bronchology. In the submitted paper the authors present their initial experience with this treatment in patients of the Pneumological Clinic in Prague-Veleslavin. In the course of 12 months since when there is a Nd:YAG laser, Sharplan Co. at the clinic, 52 patients were treated by this method. Forty of them suffered from lung cancer. Three had other types of tumours. Eight patients suffered from benign cicatricial stenoses and one female patient aspirated a foreign body. A total of 124 bronchoscopies, using a laser, were performed, on average 2.4 per patient. In 75% of patients with lung cancer recanalization was achieved, the trachea was dilated in all patients with cicatricial stenoses, however, only in one quarter of them complete restitution of the lumen was achieved. Hitherto assembled experience confirms the value of laser treatment for improving the life and its prolongation in patients with lung cancer and its importance for treatment of other endotracheobronchial processes. Three serious haemorrhages during operation were recorded, one female patient died. The use of the laser is simple, its operation smooth. PMID- 1423470 TI - [One-stage surgery in concomitant heart and lung disease]. AB - The authors evaluate the advantages and disadvantages of one-stage operations in concomitant cardiac and pulmonary diseases and define the optimal indications for this procedure. The justification of one-stage operations in selected patients is confirmed by the authors' own experience assembled in two patients. One suffered from lung cancer and ischaemic heart disease and the other one from a tuberculoma and ischaemic heart disease. The one-stage operation in both patients was without complications. PMID- 1423471 TI - [The role of ethics committees in evaluating the ethical aspects of clinical drug trials]. PMID- 1423472 TI - Morphological analysis of the neurons in the area of the hypothalamic magnocellular dorsal nucleus of the guinea pig. AB - In the guinea-pig hypothalamus, a group of enkephalinergic cells forms a well circumscribed nuclear area called the magnocellular dorsal nucleus (MDN). This nucleus gives rise to a prominent projection to the lateral septum: the hypothalamo-septal enkephalinergic pathway. In the present study, MDN neurons visualized by Golgi impregnation were subjected to morphological analysis in order to define the potential segregation of cellular types within the MDN. This study was complemented by additional observations of MDN neurons intracellularly injected by Lucifer yellow (LY) or horseradish peroxidase (HRP) during the in vitro incubation of hypothalamic slices. The following results were obtained from the analysis of 200 neurons: 163 Golgi-impregnated cells plus 37 injected cells (LY = 14; HRP = 23). Thirteen HRP-injected cells were precisely located in the MDN and 10 were located in the perifornical area surrounding the MDN. Four different cellular types were identified. Type-I neurons (41%) displayed a globular perikaryon, a variable number of primary dendrites that were poorly ramified, no preferential orientation, and an axon emerging from the perikaryon. Type-II neurons (30.5%) had a triangular perikaryon, three well-ramified primary dendrites, an orientation perpendicular to the third ventricle, and an axon emerging from the perikaryon. Type-III neurons (22%) exhibited a spindle-shaped perikaryon, two opposed well-ramified primary dendrites, an orientation perpendicular to the third ventricle, and an axon emerging from a primary dendrite. Type-IV neurons (6.5%), showed a globular perikaryon, a variable number of primary dendrites, poorly ramified dendrites, an orientation parallel to the third ventricle, and an axon whose orientation could not be identified. Neurons labeled after intracellular injection belonged to the first three cellular types. PMID- 1423473 TI - Distribution of enteric nerve cells that project to the coeliac ganglion of the guinea-pig. AB - The digestive tract of the guinea-pig, from the esophagus to the rectum, was examined in detail to determine the distribution and relative abundances of neurons in these organs that project to the coeliac ganglion and the routes by which their axons reach the ganglion. A retrogradely transported neuronal marker, Fast Blue, was injected into the coeliac ganglion. The esophagus, stomach, gallbladder, pancreas, duodenum, small intestine, caecum, proximal colon, distal colon and rectum were analysed for labelled neurons. Retrogradely labelled neurons were found only in the myenteric plexus of these organs, and in the pancreas. No labelled neurons were found in the gallbladder or the fundus of the stomach, or in the submucous plexus of any region. A small number of labelled neurons was found in the gastric antrum. An increasing density of labelled neurons was found along the duodenum. Similarly, an increasing density of labelled neurons was found from proximal to distal along the jejuno-ileum. However, the greatest densities of labelled neurons were in the large intestine. Many labelled neurons were found in the caecum, including a high density underneath its taeniae. An increasing density of labelled neurons was found along the length of the proximal colon, and labelled neurons were found in the distal colon and rectum. In total, more labelled cell bodies occurred in the large intestine than in the small intestine. The routes taken by the axons of viscerofugal neurons were ascertained by lesioning the nerve bundles which accompany vessels supplying regions of the digestive tract. Viscerofugal neurons of the caecum project to the coeliac ganglion via the ileocaeco-colic nerves; neurons in the proximal colon project to the ganglion via the right colic nerves, and neurons in the distal colon project to the ganglion via the mid colic and intermesenteric nerves. Neurons in the rectum project to the coeliac ganglion via the intermesenteric nerves. These nerves (except for the intermesenterics) all join nerve bundles from the small intestine that follow the superior mesenteric artery. All viscerofugal neurons of the caecum were calbindin-immunoreactive (calb-IR) and 94% were immunoreactive for vasoactive intestinal peptide (VIP-IR). In the proximal colon, 49% of labelled neurons were calb-IR and 85% were VIP-IR. In the distal colon, 80% of labelled neurons were calb-IR and 71% were VIP-IR. PMID- 1423475 TI - Immunocytochemical localization of Bombyx-PTTH-like molecules in neurosecretory cells of the brain of the migratory locust, Locusta migratoria. A comparison with neuroparsin and insulin-related peptide. AB - Using a monoclonal antibody directed against a synthetic pentadecapeptide corresponding to the N-terminus of the prothoracicotropic hormone (PTTH) of Bombyx mori, we report the presence of immunoreactive molecules in a large number of median neurosecretory cells of the pars intercerebralis of the migratory locust, Locusta migratoria. These cells correspond to the A1 cell type which we show to contain also neuroparsins, a family of predominant neurohormones of the migratory locust. In contrast, PTTH-like molecules are absent from A2 cells of the pars intercerebralis which contain Locusta insulin-related peptide (LIRP). Developmental studies show the presence of PTTH-related substances in neurosecretory cells of Locusta migratoria from late embryogenesis to adult development, including ageing vitellogenic female adults. PMID- 1423476 TI - Organization of cells and extracellular matrix in mesenteric arteries of spontaneously hypertensive rats. AB - Biochemical studies have been used to assess the quantitative changes in elastin and collagen in hypertensive vs. normotensive arteries. However, the relative distribution and organization of these fibrous proteins is likely to be equal in importance to their absolute amounts. In this study we have used scanning electron microscopy in association with selective digestion techniques to assess the organization of cellular and extracellular components of the tunica media of mesenteric arteries of spontaneously hypertensive rats. Superior and small mesenteric arteries were digested with acid, alkali, or bleach to exposure cells, collagen, or collagen and elastin, respectively. We observed that hypertension does not cause a qualitative change in the 3-dimensional arrangement of cells, collagen, or elastin in spontaneously hypertensive arteries when compared to normotensive arteries. However, cells in the superior artery are significantly different in overall shape and surface features when compared to cells of small arteries. These differences in surface morphology of cells are present in hypertensive and normotensive vessels and suggest that superior and small mesenteric artery cells transmit load to the isotropic matrix in different ways. In the elasto-muscular superior artery, force is transmitted across digitations throughout the cell surface. In the muscular small artery, force is transmitted across the tapered, smooth cell surface. PMID- 1423474 TI - Neuronal influence on B and H human blood-group antigen expression in rat cochlear cultures. AB - The presence of B and H human blood-group antigens was analyzed by immunocytochemistry in rat cochleas developing either in vivo or in vitro. Developing animals, on embryonic day (E) 18 and postnatal day (P) 3, were used for in vivo studies. For in vitro studies, cochleas were removed at E18 and placed for 3 or 8 days in organotypic culture either directly or after partial spiral ganglion removal. Results from epithelial regions from cochleas developing in vivo were similar to those observed in corresponding areas of direct organotypic cultures where the innervation from spiral ganglion neurons was present. Antibodies to human blood group antigens, anti B and anti AB, selectively labeled hair cells. The intensity of labeling was weak at E18, but increased at P3 in vivo or after 3-8 days in organotypic culture. Anti H antibodies showed weak labeling of the apical surface of hair cells and other epithelial cells at E18; this labeling also increased at P3 or after 3-8 days in culture. In contrast, the non-innervated regions from organotypic cultures, where ganglia were partially removed, exhibited an epithelial disorganization and no hair cell labeling with any of the antibodies studied. The present findings suggest that human blood-group antigen expression on developing cochlear hair cells of rats may be related to afferent nerve fiber influence. PMID- 1423477 TI - Immunohistochemical localisation of natriuretic peptides in the heart and brain of the gulf toadfish Opsanus beta. AB - The distribution of natriuretic peptide immunoreactivity was determined in the heart and brain of the gulf toadfish Opsanus beta using the avidin-biotin peroxidase technique. Four antisera were used: the first raised against porcine brain natriuretic peptide which cross-reacts with atrial natriuretic and C-type natriuretic peptides (termed natriuretic peptide-like immunoreactivity); the second raised against porcine brain natriuretic peptide which cross-reacts with C type natriuretic peptide but not with atrial natriuretic peptide (termed porcine brain natriuretic peptide-like immunoreactivity); the third raised against rat atrial natriuretic peptide; and the fourth raised against eel atrial natriuretic peptide. Natriuretic peptide- and porcine brain natriuretic peptide-like immunoreactivity was observed in all cardiac muscle cells of the atrium. In the ventricle, natriuretic peptide-like immunoreactivity was found in all cardiac muscle cells, however, porcine brain natriuretic peptide-like immunoreactivity was confined to muscle cells adjacent to the epicardium. There was no discernible difference in the distribution of natriuretic peptide-like immunoreactivity and porcine brain natriuretic peptide-like immunoreactivity in the brain. Immunoreactive perikarya were observed only in the preoptic region of the diencephalon, and many immunoreactive fibres were found in the telencephalon, preoptic area, and rostral hypothalamus, lateral to the thalamic region. There was no immunoreactivity in any region of the hypophysis. A pair of distinct immunoreactive fibre tracts ran caudally from the preoptic area to the thalamic region, from which fibres extended to the posterior commissure, area praetectalis, dorsolateral regions of the midbrain tegmentum, and tectum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423478 TI - Cellular differences in the regeneration of murine skeletal muscle: a quantitative histological study in SJL/J and BALB/c mice. AB - Skeletal muscle regeneration in SJL/J and BALB/c mice subjected to identical crush injuries is markedly different: in SJL/J mice myotubes almost completely replace damaged myofibres, whereas BALB/c mice develop fibrotic scar tissue and few myotubes. To determine the cellular changes which contribute to these differential responses to injury, samples of crushed tibialis anterior muscles taken from SJL/J and BALB/c mice between 1 and 10 days after injury were analysed by light and electron microscopy, and by autoradiography. Longitudinal muscle sections revealed about a 2-fold greater total mononuclear cell density in SJL/J than BALB/c mice at 2 to 3 days after injury. Electron micrographs identified a similar proportion of cell types at 3 days after injury. Autoradiographic studies showed that the proportions of replicating mononuclear cells in both strains were similar: therefore greater absolute numbers of cells (including muscle precursors and macrophages) were proliferating in SJL/J muscle. Removal of necrotic muscle debris in SJL/J mice was rapid and extensive, and by 6 to 8 days multinucleated myotubes occupied a large part of the lesion. By contrast, phagocytosis was less effective in BALB/c mice, myotube formation was minimal, and fibrotic tissue conspicuous. These data indicate that the increased mononuclear cell density, more efficient removal of necrotic muscle, together with a greater capacity for myotube formation in SJL/J mice, contribute to the more successful muscle regeneration seen after injury. PMID- 1423479 TI - Cellular immunity in an annelid (Nereis diversicolor, Polychaeta): production of melanin by a subpopulation of granulocytes. AB - We attempted to identify the nature and origin of the pigment produced by the marine worm Nereis diversicolor in order to isolate, in inert brown capsules, foreign objects introduced into its body cavity. This brown pigment, characterized by cytochemical techniques, could be a melanin. The activity of the enzyme phenoloxidase responsible for melanin biosynthesis was detected by enzyme cytochemistry techniques in vacuoles and the Golgi apparatus of coelomocytes activated by the presence of foreign bodies. Morphological techniques combined with a monoclonal immunological probe enabled us to establish that the "G2" granulocytes contain both the precursor of the pigment in dense bodies and the capacity for phenoloxidase synthesis when activated to encapsulate foreign bodies. The "G2" granulocyte may therefore be compared to a melanocyte in which melanin is not stored as in mammals, but immediately extruded following synthesis in the form of a thick fluid. PMID- 1423480 TI - Differential expression of four genes encoding molluscan insulin-related peptides in the central nervous system of the pond snail Lymnaea stagnalis. AB - In the pond snail Lymnaea stagnalis, the growth regulating system consists of (1) about 200 neuroendocrine light green cells, located in four clusters in the cerebral ganglia, and (2) the paired canopy cells, located in the lateral lobes. These cells express genes encoding the molluscan insulin-related peptides (MIPs). Six MIP genes have previously been identified. Four of these (I, II, III and V) are expressed in the light green cells and the canopy cells. The MIP-VI gene is a pseudogene. In the present in situ hybridization study, using oligonucleotide probes specific to the transcripts of MIP-I, -II, -III, -IV and -V, no signal was obtained with the MIP-IV probe, indicating that gene IV is also a pseudogene. With the other four probes, two types of light green cells were distinguished. Type-A cells express all four MIP genes, whereas type-B cells do not (or only faintly) express the MIP-I gene. Gene III is relatively strongly expressed in type-B cells. Genes II and V are moderately expressed in both cell types. Type-A cells are mainly located in the periphery of the clusters, whereas type-B cells are present in the center. The canopy cell resembles type-A light green cells. The expression levels of the MIP-II and MIP-V genes are low in the canopy cell. The expression pattern of the MIP genes correlates with the staining pattern of the anti-MIP-C antibody, which has been raised to a synthetic C-fragment shared by MIP-I, -II and -V. Type-A cells stain more intensely with the antibody than type-B cells. PMID- 1423481 TI - The origin of the luteinizing hormone-releasing hormone (LHRH) neurons in newts (Cynops pyrrhogaster): the effect of olfactory placode ablation. AB - Neurons containing luteinizing hormone-releasing hormone (LHRH) are first detected in newt embryos (Cynops pyrrhogaster) in the olfactory epithelium and ventromedial portion of the olfactory nerve, after which they sequentially appear in the intracerebral course of the terminal nerve at prometamorphosis, and in the septo-preoptic area at postmetamorphosis. In adults, however, LHRH-immunoreactive cells are rarely seen in the nasal region, and their distribution shifts into the brain, suggesting their migration. In order to ascertain the origin and possible migration route of these neurons in newt larvae, the effect of unilateral or bilateral olfactory placodectomy on the LHRH neuronal system has been studied. Removal of the olfactory placode results in the absence of LHRH-immunoreactive cells in the nasal and brain regions of the operated side, whereas the subsequent growth and the LHRH-immunoreactive cellular distribution in the contralateral side are identical to those of normal larvae. Following bilateral placodectomy, no LHRH immunoreactivity is detected on either side of the olfactory-brain axis. These results suggest that LHRH neurons of the newt, Cynops pyrrhogaster, originate in the olfactory placode and then migrate into the brain during embryonic development. PMID- 1423482 TI - Widespread tissue distribution of rabbit calreticulin, a non-muscle functional analogue of calsequestrin. AB - Calreticulin was identified in a variety of rabbit tissues by Western blot analysis. Indirect immunofluorescence studies on cultured cells or frozen sections from the corresponding tissues revealed that the protein was distributed to the endoplasmic reticulum or sarcoplasmic reticulum. Calreticulin was found to be an abundant calcium-binding protein in non-muscle and smooth muscle cells and a constituent calcium-binding protein in cardiac and skeletal muscle. From the immunoblot data, calreticulin may exist as an isoform in rabbit neural retina. The present study establishes the ubiquity of calreticulin in intracellular calcium binding. PMID- 1423483 TI - Morphogenesis of the photoreceptor outer segment during postnatal development in the mouse (BALB/c) retina. AB - Disc formation of rod photoreceptor cells in developing BALB/c mice retinas was studied by rapid freeze, freeze-substitution, freeze-etching, immunocytochemistry, and myosin S-1 decoration methods. Freeze-substituted photoreceptor cells contained variously shaped vesicles in the apical swelling of the connecting cilium or the base of the outer segment during postnatal development. Rapid freezing successfully arrested pinocytosis; the fusion of small vesicles to give large ones, and the compression of certain vesicles (0.3 0.6 micron) appears to lead gradually to the formation of the so-called discs. We therefore propose that membranous discs are formed by the fusion of small pinocytotic vesicles and their subsequent compression. Discs formed in this way were partially stacked, but were ordered at random during the early developmental stages. During development, a partial stack of discs was progressively rearranged to a regular form as seen in mature outer segments. Cytoskeletal actin was expected to be involved in the disc formation; it was demonstrated in the distal axoneme of the connecting cilium during development and showed no change in its distribution. However, the polarity of the actin filaments, as revealed by myosin S-1 decoration in early developmental stages, was much more variable than in the adult. Barbed ends of actin filaments were associated with the plasma membrane or the membrane of vesicles. We also found actin filaments coiled up helically on ciliary microtubules. PMID- 1423484 TI - Smooth muscle cells in the walls of ovarian follicles in the Japanese quail. AB - The walls of pre-ovulatory follicles of the Japanese quail were examined at the ultrastructural level for the presence of cells displaying the typical morphological features of smooth muscle cells. These characteristics were found in the cells of the chordae, the tunica albuginea, and the theca externa. Small, elongated cells, containing microfilaments, were observed in the theca of prelampbrush follicles localized in the ovarian cortex. These thecal cells were considered as the putative precursors of the thecal smooth muscle cells of the pre-ovulatory follicle. The difference between the smooth muscle cells of the pre ovulatory follicle and those in the wall of the most recent post-ovulatory follicle is the contracted state of the latter, which is most evident in the cells of the theca externa. It can be concluded that the cells of the theca externa are smooth muscle cells which are mainly contracted during the ovulatory process. A comparison was made with other vertebrate species. PMID- 1423485 TI - Dye coupling in the corneal endothelium: effects of ouabain and extracellular calcium removal. AB - The effects of ouabain and extracellular calcium removal on gap junctional coupling of isolated rabbit corneal endothelium was examined using a modified dye spread technique. This technique is a modification of a microelectrode procedure that now utilizes patch electrodes connected to a current-clamp circuit for dye iontophoresis and a shuttering system in the excitation light path to reduce phototoxic effects in the monolayer. It was found that a significant degree of junctional uncoupling occurred after 45 min of exposure to ouabain, quantified as a reduction in the effective diffusion coefficient of injected Lucifer yellow CH: 1.74 x 10(-7) cm2/s (control) versus 0.43 x 10(-7) cm2/s (ouabain-treated). It was also determined that no gap junctional uncoupling occurs after extended exposure (up to 3.5 h) to a calcium-free extracellular environment. PMID- 1423486 TI - Postembryonic development of leucokinin I-immunoreactive neurons innervating a neurohemal organ in the turnip moth Agrotis segetum. AB - In the abdominal ganglia of the turnip moth Agrotis segetum, an antibody against the cockroach neuropeptide leucokinin I recognizes neurons with varicose fibers and terminals innervating the perisympathetic neurohemal organs. In the larva, the abdominal perisympathetic organs consist of a segmental series of discrete neurohemal swellings on the dorsal unpaired nerve and the transverse nerves originating at its bifurcation. These neurohemal structures are innervated by varicose terminals of leucokinin I-immunoreactive (LKIR) fibers originating from neuronal cell bodies located in the preceding segment. In the adult, the abdominal segmental neurohemal units are more or less fused into a plexus that extends over almost the whole abdominal nerve cord. The adult plexus consists of peripheral nerve branches and superficial nerve fibers beneath the basal lamina of the neural sheath of the nerve cord. During metamorphosis, the LKIR fibers closely follow the restructuration of the perisympathetic organs. In both larvae and adults the LKIR fibers in the neurohemal structures originate from the same cell bodies, which are distributed as ventrolateral bilateral pairs in all abdominal ganglia. The transformation of the series of separated and relatively simple larval neurohemal organs into the larger, continuous and more complex adult neurohemal areas occurs during the first of the two weeks of pupal life. The efferent abdominal LKIR neurons of the moth Agrotis segetum thus belong to the class of larval neurons which persist into adult life with substantial peripheral reorganization occurring during metamorphosis. PMID- 1423487 TI - Postnatal development and testosterone-dependence of GP-83 and GP-49, two sperm maturation-related glycoproteins in BALB/c mouse epididymis. AB - The secretion of sperm maturation-related molecules by the epididymis is subjected to developmental and hormonal regulation. In the BALB/c mouse, we found that GP-83 and GP-49, two sperm maturation-related glycoproteins, were secreted by the epididymis. The present study investigated the postnatal development and testosterone-dependence of these two molecules. Histochemical localization in paraffin sections revealed that wheat-germ agglutinin (WGA)-binding sites were first present in the epididymis of 4-week-old mice. The distribution of WGA binding sites was the same as that of more mature mice, i.e., it was first found in the principal cells of the corpus epididymidis, and gradually appeared in the contents of epididymal tubules. On WGA blots, GP-83 and GP-49 were identified in the corpus, and GP-83 was identified in the cauda of the epididymis. In mice that had received unilateral orchiectomy at 4 weeks of age, GP-83 and GP-49 were present in both intact and orchiectomized epididymides 4 weeks after the operation. In the epididymides of mice that had received bilateral orchiectomy, GP-83 and GP-49 were barely identifiable. However, the presence of these two molecules was restored if testosterone was supplemented immediately after orchiectomy. These results indicate that GP-83 and GP-49 are secreted de novo in the epididymis, and that the secretion of these two molecules is developmentally regulated and androgen-dependent. PMID- 1423488 TI - Quantitative morphology of stimulation-induced damage in rabbit fast-twitch skeletal muscles. AB - The purpose of this study was to examine the contention that stimulation-induced damage, resulting in degeneration with subsequent regeneration, plays a major role in the transformation of fibre type brought about by chronic electrical stimulation. Data from histological and histochemical sections of 9-day stimulated rabbit fast-twitch muscles were analysed with multivariate statistical techniques. Fibre degeneration and regeneration varied non-systematically between sample areas at any given cross-sectional level. In the extensor digitorum longus muscle, but not in the tibialis anterior, there was more degeneration in proximal than in distal portions of the muscle. The extensor digitorum longus muscle consistently showed more degeneration than the tibialis anterior muscle. Degeneration was less extensive for an intermittent pattern of stimulation that delivered half the aggregate number of impulses of continuous stimulation. Degeneration and regeneration varied markedly between individual rabbits in each of the groups. Sections that revealed the most degeneration and regeneration also had more fibres that reacted positively with an anti-neonatal antibody. Rigorous analysis of different sources of variation has helped to explain apparent conflicts in the literature. The incidence of muscle fibre damage in the stimulated tibialis anterior muscle is low, showing that the contribution of degenerative-regenerative phenomena to fibre type conversion in this muscle is insignificant. PMID- 1423489 TI - Bromodeoxyuridine-immunohistochemistry on cellular differentiation and migration in the fundic gland of Xenopus laevis during development. AB - Cellular differentiation and migration in the fundic glands of adult and larval Xenopus laevis have been examined using bromodeoxyuridine-immunohistochemistry. In the adult fundic gland, cumulative labeling with bromodeoxyuridine revealed a proliferative cell zone between the surface mucous cells and mucous neck cells, in what is referred to as the neck portion of the gland. The labeling-index of mucous neck cells had rapidly increased by week-5. The labeling-index of oxynticopeptic cells showed a more delayed increase until week-7, coincident with the decrease in the labeling of mucous neck cells. In the immature fundic glands of larvae, the labeled proliferating cells were randomly distributed throughout the developing gastric mucosa. During metamorphosis, the labeling-index of immature epithelial cells was highest at stage 63. Following administration of bromodeoxyuridine at this stage, there was no significant loss of labeled epithelial cells during the metamorphosing period. Furthermore, there was no significant difference in the labeling-indices among the epithelial cells, such as surface mucous cells/generative cells, mucous neck cells, and oxynticopeptic cells, 7 days after administration. Cellular differentiation and migration pathways of epithelial cells in the fundic gland of adult X. laevis and its larvae are discussed. PMID- 1423490 TI - Immunolocalization of inhibin alpha-subunit in the human testis. A light- and electron-microscopy study. AB - The localization of inhibin alpha-subunit in the human testis was studied at the light- and electron-microscope level with immunostaining techniques. Antibodies against specific fragments of porcine and human inhibin alpha-subunits were utilized. At light microscopy, inhibin alpha-subunit immunoreactivity was detected in Sertoli cells, spermatocytes and in some Leydig cells. At electron microscopy, gold labeling was found in the cisternae of the Golgi apparatus and in the endoplasmic reticulum of Sertoli and Leydig cells. Gold labeling for inhibin was also found in coated vesicles in the cytoplasm of Sertoli cells as well as in coated pits and coated vesicles in the cytoplasm of some spermatocytes. The results of the present study suggest that, in the human testis, inhibin is produced by Sertoli and Leydig cells and is taken up by spermatocytes, on which it might act in a paracrine manner. PMID- 1423491 TI - In vivo effects of tunicamycin on chondrocytes of rat mandibular condyles as revealed by lectin cytochemistry. AB - The in vivo effects of tunicamycin on the glycosylation of proteoglycans and link protein in rat mandibular condylar chondrocytes were studied by ultrastructural lectin histochemistry. The binding of wheat-germ agglutinin was shown by using anti-lectin antibody followed by protein A-gold complex. In normal rats, wheat germ agglutinin labeling was restricted to trans cisternae and vacuoles of the Golgi complex, whereas it was observed in neither the cis region of the Golgi complex nor in the rough endoplasmic reticulum. By 3 h after the drug administration, wheat-germ agglutinin binding sites on the disorganized Golgi vacuoles were dramatically reduced in number. At 6 h after the drug administration, the lectin binding sites on the Golgi vacuoles were restored. These results demonstrate that the in vivo use of tunicamycin in combination with histochemical analysis using lectin probes is of significant value for the study of protein glycosylation in chondrocytes of the rat mandibular condyle. PMID- 1423492 TI - Neuropeptides regulate the cardiac activity of a prosobranch mollusc, Rapana thomasiana. AB - Involvement of neuropeptides in the regulation of cardiac activity in a prosobranch mollusc, Rapana thomasiana, was studied physiologically as well as immunohistochemically. A catch-relaxing peptide (CARP) showed strong inhibitory effects on the heart with a lower threshold than acetylcholine. The action of CARP was in contrast to that of another neuropeptide, FMRFamide, which has previously been shown to enhance the heart beat. Benzoquinonium blocked the effects of acetylcholine and stimulation of right cardiac nerves 1 and 3 b, but not those of CARP, suggesting that the effects of nerve stimulation are mainly due to the release of acetylcholine. Immunohistochemical examinations demonstrated that FMRFamide-like and CARP-like immunoreactive neurons are distributed in the visceral ganglia. Although a neuron appeared to show weak immunoreactivity to both antisera, evidence for the coexistence of peptides in a single neuron was not exhibited. Positive immunoreactivity to FMRFamide and CARP antisera also appeared in right cardiac nerves 1 and 3. In the heart, FMRFamide- and CARP-like immunoreactive fibers were restricted to the atrium and the aortic end of the ventricle, consistent with the morphological observation of innervation. The present results suggest that FMRFamide- and CARP-like peptides are involved in regulating the heart beat. PMID- 1423493 TI - Fine structure of the neurohemal sinus gland of the shore crab, Carcinus maenas, and immuno-electron-microscopic identification of neurosecretory endings according to their neuropeptide contents. AB - The sinus gland of the shore crab, Carcinus maenas, is a compact assembly of interdigitating neurosecretory axon endings abutting upon the thin basal lamina of a central hemolymph lacuna. Four types of axon endings are distinguishable by the size distribution, shape, electron density and core structure of their neurosecretory granules. One additional type of axon ending is characterized by electron-lucent vacuoles and vesicles. The axon profiles are surrounded by astrocyte-like glial cells. Various fixations followed by epoxy- or Lowicryl embedding were compared in order to optimize the preservation of the fine structure of the granule types and the antigenicity of their peptide hormone contents. By use of specific rabbit antisera, the crustacean hyperglycemic, molt inhibiting, pigment-dispersing, and red-pigment-concentrating hormones were assigned to the four distinct granule types which showed no overlap of immunostaining. Epi-polarization microscopy and ultrathin section analysis of immunogold-stained Lowicryl-embedded specimens revealed that immunoreactivity to Leu-enkephalin and proctolin is co-localized with molt-inhibiting hormone immunoreactivity in the same type of granule. The size and core structure of the immunocytochemically identified granule types vary little with the different pretreatments but, in some cases, to a statistically significant extent. The present results are compared with those from earlier studies of sinus glands in different crustaceans. The methods of granule identification used in this study supplement the classical approach in granule typing; they are easier to perform and more reliable for the analysis of release phenomena in identified secretory neurons supplying the neurohemal sinus gland. PMID- 1423494 TI - Pituitary adenylate cyclase-activating polypeptide (PACAP): occurrence in rodent pancreas and effects on insulin and glucagon secretion in the mouse. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that occurs in several tissues, e.g., in the gut. We have studied PACAP-like immunoreactivity in the pancreas of rat and mouse, and the effects of PACAP-38 on basal and stimulated insulin and glucagon secretion in the mouse. Immunofluorescence staining demonstrated the presence of PACAP-like immunoreactivity in nerve fibers in both the rat and mouse pancreas. The nerve fibers were seen in the exocrine pancreas and surrounding the islets. Occasionally, the nerve fibers occurred within the islets. Most PACAP-positive nerve fibers innervated the intrapancreatic ganglia, although no nerve cell bodies contained PACAP-like immunoreactivity. In-vivo experiments in mice revealed that basal plasma glucagon levels were increased by PACAP-38 injected intravenously at dose levels exceeding 1.8 nmol/kg. Furthermore, PACAP-38 (7 nmol/kg) potentiated the plasma glucagon response to the cholinergic agonist carbachol (0.16 mumol/kg). This potentiation was reduced to simple addition by pretreatment with a combined alpha- and beta-adrenergic blockade by phentolamine (35 mumol/kg) and propranolol (8.5 mumol/kg). Moreover, PACAP-38 inhibited a carbachol-induced increase in the level of plasma insulin in the absence but not in the presence of adrenergic blockade. PACAP-38 increased basal plasma insulin levels and increased basal plasma glucose levels 6 min and 10 min, respectively, after injection of the peptide. We conclude that PACAP-like immunoreactivity exists in nerve fibers innervating the mouse and rat pancreas, particularly the intrapancreatic ganglia, and that PACAP-38 augments both basal and carbachol stimulated glucagon secretion in the mouse. PMID- 1423495 TI - The role of cell proliferation and migration in the development of a neo-intimal layer in veins grafted into arteries, in rats. AB - The development of a thickened (hyperplastic) fibro-cellular neo-intima is a significant event in the adaptation of a vein grafted into an artery. The histogenesis of tissues in vein grafts was explored in a rat model where the source of endothelial and smooth muscle cells was from the adjacent artery. Cell proliferation was assessed by the incorporation of tritiated thymidine and autoradiography, up to 18 months after grafting. Cell migration was detected by prelabelling in the first 5 days after grafting and sampling at later times. The proliferation of cells in the arterial media adjacent to the graft was elevated above control levels as early as 2 days after grafting; it was maximal at 3 days and returned to low levels by day 21. During the first week, prelabelled smooth muscle cells in the tunica media of the adjacent artery migrated to the subendothelial space, where they continued to proliferate to produce arterial intimal hyperplasia. The migration of endothelial and smooth muscle cells proceeded across the anastomosis to populate the vein graft neo-intima, where smooth muscle cells continued to proliferate until 28 days after grafting. Cell migration and proliferation were significant factors in the histogenesis of vein graft neo-intimal hyperplasia in this model. These processes were controlled, perhaps by local regulatory factors, to form a vein graft, the wall of which was similar in thickness and structure to that of the host artery. PMID- 1423496 TI - Calbindin D-28k-positive neurons in the rat olfactory bulb. An immunohistochemical study. AB - We have studied the distribution of calbindin D-28k immunoreactivity in the rat olfactory bulb using specific monoclonal antibodies and the avidin-biotin immunoperoxidase method. The largest number of positive neurons was located in the periglomerular layer. These neurons were identified as periglomerular cells; they have been described also by other authors as calbindin-positive elements. Close to these neurons, a second population of nerve cells was identified as superficial short-axon neurons. The remaining layers showed a smaller number of stained elements. Other labeled neurons were located along the external border of the external plexiform layer; the scarce neurons marking its internal border were identified as van Gehuchten cells. No immunoreactive structures were found in the mitral cell layer, although we observed another population of immuno-stained short-axon cells at its internal border. Some reactive structures, identified by us as horizontal and vertical cells of Cajal, were located in the boundary zone between the internal plexiform layer and the granule layer. In the white matter, we found a neuronal type characterized by its large size and oriented arborization of varicose dendrites. PMID- 1423497 TI - Glomerular bypass shunts and distribution of glomeruli in the kidney of the lesser spotted dogfish, Scyliorhinus caniculus. AB - Scanning electron microscopy of corroded resin casts of the renal vasculature of Scyliorhinus caniculus has revealed a novel vascular pathway arising from the afferent arteriole and bypassing the glomerulus. This glomerulus bypass shunt occurred in 36% of the glomerular casts examined. The shunt ran to join a peritubular network of capillaries and thereby offers the potential to vary the degree of glomerular perfusion and control the proportion of active glomeruli. In 29% of glomeruli two efferent arterioles drained the capillary knot. Glomeruli were located close to the dorsal margin of the posterior mass of the kidney, and towards the lateral edge of the anterior lobes of the kidney of female dogfish. In male dogfish, glomeruli were evenly distributed through the posterior mass of kidney, while in female dogfish 89% of glomeruli occurred in the posterior mass and 11% of glomeruli were located within the small anterior lobes. PMID- 1423498 TI - Organization of the ciliary basal apparatus in embryonic cells of the sea urchin, Lytechinus pictus. AB - The basal apparatus of embryonic cells of the sea urchin Lytechinus pictus was examined by transmission electron microscopy and compared with the basal apparatus of other metazoan cells. The basal apparatus in these cells is associated with a specialized region of the apical cell surface that is encircled by a ring of microvilli. The basal apparatus includes several features that are common to all ciliated cells, including a basal body, basal foot, basal foot cap, and striated rootlet. However, a component not seen in the basal apparatus of other species has been observed in these cells. This structure is continuous with the striated rootlet, and its ultrastructure indicates that it is composed of the same components as the rootlet. This structure extends from the junction of the basal body and striated rootlet to the cortical region that surrounds the basal body. Based on its morphology and position, this structure is referred to as a striated side-arm. The striated side-arm is always aligned in the plane of the basal foot. Thus, both of these structures extend from the basal body in the plane of the effective stroke. It is suggested that the striated side-arm serves to stabilize the basal apparatus against force exerted by the cilium. PMID- 1423499 TI - Localization of calcitonin gene-related peptide and islet amyloid polypeptide in the rat and mouse pancreas. AB - It was previously demonstrated that the two chemically related peptides calcitonin gene-related peptide (CGRP) and islet amyloid polypeptide (IAPP) both occur in the pancreas. We have now examined the cellular localization of CGRP and IAPP in the rat and the mouse pancreas. We found, in both the rat and the mouse pancreas, CGRP-immunoreactive nerve fibers throughout the parenchyma, including the islets, with particular association with blood vessels. CGRP-immunoreactive nerve fibers were regularly seen within the islets. In contrast, no IAPP immunoreactive nerve fibers were demonstrated in this location. Furthermore, in rat islets, CGRP immunoreactivity was demonstrated in peripherally located cells, constituting a major subpopulation of the somatostatin cells. Such cells were lacking in the mouse islets. IAPP-like immunoreactivity was demonstrated in rat and mouse islet insulin cells, and, in the rat, also in a few non-insulin cells in the islet periphery. These cells seemed to be identical with somatostatin/CGRP immunoreactive elements. In summary, the study shows (1) that CGRP, but not IAPP, is a pancreatic neuropeptide both in the mouse and the rat; (2) that a subpopulation of rat somatostatin cells contain CGRP; (3) that mouse islet endocrine cells do not contain CGRP; (4) that insulin cells in both the rat and the mouse contain IAPP; and (5) that in the rat, a non-insulin cell population apparently composed of somatostatin cells stores immunoreactive IAPP. We conclude that CGRP is a pancreatic neuropeptide and IAPP is an islet endocrine peptide in both the rat and the mouse, whereas CGRP is an islet endocrine peptide in the rat. PMID- 1423500 TI - Immunolocalization of synexin (annexin VII) in adrenal chromaffin granules and chromaffin cells: evidence for a dynamic role in the secretory process. AB - Synexin (annexin VII) is a Ca(2+)- and phospholipid-binding protein which has been proposed to play a role in Ca(2+)-dependent membrane fusion processes. Using a monoclonal antibody against synexin, Mab 10E7, and immunogold, we carried out a semiquantitative localization study of synexin in bovine adrenal medullary chromaffin granules, and in resting and nicotine-stimulated adrenal chromaffin cells. Isolated chromaffin granules contained very little synexin, whereas chromaffin granules aggregated with synexin (24 micrograms/mg) and Ca2+ (1 mM) clearly showed synexin-associated immunogold particles in the vicinity of the granule membrane (1.88 gold particles per granule profile). In isolated, cultured adrenal chromaffin cells, synexin was present in the nucleus (5.5 particles/microns 2) and in the cytosol (5.3 particles/microns 2), but mainly around the granule membrane in the granular cell area (11.7 particles/microns 2). During the active phase of cholinergically stimulated catecholamine secretion, the amount of synexin label was reduced by 33% in the nucleus, by 23% in the cytosol, and by 51% in the granule area. The plasma membrane contained a small amount of synexin, which did not significantly change upon stimulation of the cells. We conclude that synexin is involved in the secretory process in chromaffin cells. PMID- 1423501 TI - Species variability in the expression of met- and leu-enkephalin-like immunoreactivity in mammalian Merkel cell dense-core granules. A light- and electron-microscopic immunohistochemical study. AB - Immunogold staining failed to show met-enkephalin immunoreactivity in the Merkel cell dense-core granules of rats when examined by electron microscopy, but showed gold particle staining in the Merkel cell dense-core granules of mice and nude mice. Merkel cells of hamster, guinea pig, rabbit, cat and dog were also examined using a similar method, and different antisera dilutions. Immunogold particles were consistently found in the dense-core granules of mice and nude mice at all antisera dilutions, but not in the other species, except in the dog, where a very low labelling response was encountered. Merkel cells from skin touch domes or sinus hair follicles, did not exhibit any difference in peptide expression as far as met-enkephalin immunoreactivity was concerned. In addition, all species studied, including mice and nude mice, did not show leu-enkephalin immunoreactivity in their Merkel cell dense-core granules. It is concluded that species variability in peptide expression occurs in the Merkel cell dense-core granules, and may be closely related to the different methodologies used. PMID- 1423502 TI - Some peptide-like colocalizations in endocrine cells of the pyloric caeca and the intestine of Oncorhynchus mykiss (Teleostei). AB - The coexistence of immunoreactivities to cholecystokinin, glucagon, glucagon-like peptide 1, salmon pancreatic polypeptide, neuropeptide tyrosine, and peptide tyrosine tyrosine was studied immunocytochemically, revealing for the first time in fish intestine the existence in the same cell of immunoreactivities to cholecystokinin-glucagon/glucagon-like peptide 1, cholecystokinin-salmon pancreatic polypeptide, glucagon/glucagon-like peptide 1-salmon pancreatic polypeptide, glucagon/glucagon-like peptide 1-neuropeptide tyrosine, salmon pancreatic polypeptide tyrosine tyrosine, and glucagon/glucagon-like peptide 1 peptide tyrosine tyrosine. Colocalization of cholecystokinin-salmon pancreatic polypeptide was observed only in the pyloric caeca of the rainbow trout Oncorhynchus mykiss, while the other colocalizations also occurred in proximal and middle intestinal segments. In all cases, endocrine cells immunoreactive to only one of the paired antisera were detected except for anti-glucagon and anti glucagon-like peptide 1, which always immunostained the same cells. PMID- 1423503 TI - Dark and light zones of germinal centres of the human tonsil: an ultrastructural study with emphasis on heterogeneity of follicular dendritic cells. AB - The cellular composition of the dark and light zones of germinal centres in human tonsils was quantitatively determined by electron microscopy. In addition to the well known germinal-centre B-cells, we defined the cleaved blast as a new distinct cell type in the germinal centre. The dark and the light zones clearly differed in their content of lymphoid and non-lymphoid germinal-centre cells. The dark zone was characterized by higher frequencies of cleaved blasts and small centroblasts, a higher blast-centrocyte ratio and a higher incidence of mitotic figures. In contrast, the light zone had higher frequencies of centrocytes, centroplasmacytoid cells, lymphocytes and follicular dendritic cells (FDC) and an inverted blast-centrocyte ratio. Seven distinct appearances of FDC (FDC.1-FDC.7) could be recognized on the basis of their ultrastructure. The distribution pattern of these subtypes differed between the dark and light zone. The undifferentiated subtypes FDC.2 and FDC.3 predominated in the dark zone. In contrast, the highly differentiated subtypes FDC.4 and FDC.5 were present at a much higher density in the light zone. These findings suggest that the dark and light zones are different compartments with regard to proliferation and differentiation of germinal-centre B-cells and that both compartments have a specific microenvironment influenced by FDC. PMID- 1423504 TI - A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: evidence for reduced content in Hirschsprung's disease. AB - A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), exhibits sequence homology with vasoactive intestinal polypeptide (VIP) and occurs in the mammalian brain, lung and gut. The distribution of PACAP in ganglionic and aganglionic portions of the large intestine of patients with Hirschsprung's disease was examined by immunohistochemistry and radioimmunoassay. PACAP-immunoreactive nerve fibers were distributed in all layers of the ganglionic and aganglionic segments of the intestine, although they were less numerous in the latter, and PACAP-immunoreactive nerve cell bodies were seen in the ganglionic portion of the intestine. The concentration of immunoreactive PACAP was lower in the aganglionic than in the ganglionic segment of the intestinal wall. PACAP and VIP were found to coexist in both ganglionic and aganglionic segments of the intestine. Apparently, PACAP participates in the regulation of gut motility. The scarcer PACAP innervation of the aganglionic segment may contribute to the defect in intestinal relaxation seen in patients with Hirschsprung's disease. PMID- 1423506 TI - Ultrastructural evidence of indirect and direct autonomic innervation of human Leydig cells: comparison of neonatal, childhood and pubertal ages. AB - Recent physiological studies have indicated an autonomic influence on the secretion of testosterone from Leydig cells in humans and laboratory animals. Furthermore, a few studies have shown enhanced autonomic control of Leydig cell function in immature, relative to mature, laboratory animals. In the current ultrastructural study of the human testicular interstitium the morphology of autonomic components is described from neonatal, childhood and pubertal ages. Autonomic nerve fibers and varicosities with neurotransmitter vesicles are described in proximity to Leydig cells. The observed autonomic terminals are classified by vesicle morphology into three general types: (1) Type I with predominantly small agranular vesicles (30-60 nm) and occasional larger granular vesicles (100 nm). This type is morphologically consistent with being cholinergic. (2) Type II with predominantly small granular vesicles (30-60 nm), as well as sporadic large granular vesicles. These are morphologically consistent with adrenergic terminals. (3) Type III which exhibit numerous large granular vesicles of mixed size. Evidence of autonomic terminals is encountered most frequently in childhood biopsies, age 3 to 10 years. The neonatal specimen (4 months) is noteworthy in that many of the Schwann cells appear immature and no adrenergic terminals are observed. In contrast, terminals morphologically consistent with being adrenergic are common in the childhood series of biopsies. Although the vast majority of the autonomic terminals are associated with Leydig cells indirectly as "boutons en passant", separated by approximately 150 nm to more than a micron, evidence of direct contact (20 nm) of autonomic terminals with Leydig cells is presented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423505 TI - Distribution of the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein in human tissues. AB - The hepatic alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor-related protein (LRP) binds and endocytoses alpha 2-macroglobulin proteinase complexes in plasma. In addition, it binds lipoproteins, a novel 40 kDa protein, and complexes between plasminogen activators and plasminogen activator inhibitor type-1. This study shows, for the first time, the tissue distribution of alpha 2MR/LRP as determined by immunohistochemistry with specific monoclonal antibodies. The analysis revealed alpha 2MR/LRP-expression in a restricted spectrum of cell types, including neurons and astrocytes in the central nervous system, epithelial cells of the gastrointestinal tract, smooth muscle cells, fibroblasts, Leydig cells in testis, granulosa cells in ovary, and dendritic interstitial cells of kidney. Monocyte-derived cells displayed marked alpha 2MR/LRP expression in the phagocytes of liver, lung and lymphoid tissues, but no or low expression in antigen-presenting cells including Langerhans' cells of the skin. The high abundance of alpha 2MR/LRP in certain cell types of most organs suggests two main routes for alpha 2MR/LRP-mediated ligand clearance: (1) systemic removal in liver of circulating ligands, and (2) non-hepatic interstitial removal in different organs, including the brain. PMID- 1423507 TI - Histological distribution and developmental changes of tropomyosin isoforms in three chicken digestive organs. AB - Histological localization of tropomyosin isoforms in three digestive organs from embryonic and adult chickens was performed by using rabbit antisera against chicken skeletal muscle tropomyosin and against low-Mr-type tropomyosin from chicken small intestine mucosa. The former antiserum (named TM-SH) reacted with alpha, beta, and high-Mr-type isoforms, and the latter (named TM-HL) reacted with alpha, beta, high-Mr-type and low-Mr-type isoforms, alpha and beta Isoforms were detected in muscle cells of the muscular layer and the muscularis mucosa. Low-Mr type isoforms, however, were detected along the cell membrane and cytoplasm of almost all nonmuscle cells, especially in terminal webs of epithelial cells. Developmental changes of tropomyosin isoforms in digestive organs were studied by two-dimensional gel electrophoresis and image analysis. The relative amounts of alpha and beta isoforms increased in the course of development, but those of low Mr-type and high-Mr-type isoforms decreased. PMID- 1423509 TI - Electron microscopy of a double helical tubular filament in keyhole limpet (Megathura crenulata) hemolymph. AB - A approximately 25 nm hollow double helical filament has been detected ultrastructurally in the cell-free supernatant from hemolymph of the keyhole limpet Megathura crenulata (Gastropoda: Prosobranchia: Fissurellidae). Subsequently, much higher concentrations of this material were found in the cell pellet from hemolymph. Both negative staining and thin sectioning have been performed in an attempt to obtain a preliminary structural characterization of this new filament. It is proposed that the filaments are released or secreted from blood hemocytes in response to bleeding, but it has not been possible to define absolutely an intracellular organelle containing this material. It is shown that the hollow filaments, which have fine fibrillar surface extensions, are readily distinguishable from collagen fibrils and from tubular (multi decameric) keyhole limpet hemocyanin (KLH). PMID- 1423508 TI - Correlation of extracellular matrix components with the cytoarchitecture of mouse Peyer's patches. AB - The distribution patterns of extracellular matrix elements were determined to ascertain whether they play a role in the localization of lymphocytes in discrete T-cell, B-cell and dome antigen-processing domains within Peyer's patches. Antibodies against collagen types I, III and IV, laminin and fibronectin were applied to cryosections of mouse Peyer's patches and localized by direct or indirect immunoperoxidase methods. T-cell domains were identified with a monoclonal antibody against Thy-1.2. Labeled reticular fibers in distinctive patterns were more numerous in parafollicular and dome areas than within follicles. Germinal centers contained few such fibers. In parafollicular areas, fibers were oriented predominantly toward follicle domes; their distribution corresponded to T-cell zones and lymphocyte traffic areas, with their orientation being parallel to the migration pathways of lymphocytes from high endothelial venules to the antigen-processing domes. Subepithelial and subendothelial basal laminae were immunopositive for type-IV collagen, laminin and fibronectin. The dome subepithelial basal lamina had pore-like discontinuities through which lymphocytes migrated to and from the epithelium. The correspondence of the distribution patterns of extracellular matrix to specific functional domains of Peyer's patches suggests that this matrix provides a structural framework for lymphocyte migration and localization. PMID- 1423510 TI - Immunohistochemical localization and radioenzymatic measurements of serotonin (5 hydroxytryptamine) in hearts of Aplysia and several bivalve mollusks. AB - Serotonin immunoreactivity was localized in hearts of the opisthobranch gastropod, Aplysia californica (sea hare) and several species of bivalve mollusks, the heterodonts, Mercenaria mercenaria (quahog or cherry stone clam), Protothaca staminea (little neck clam), and the pteriomorphs, Hinnites multirugosus (rock scallop), Crassostrea virginica (eastern oyster), Mytilus edulis (eastern mussel), and Geukensia demissa (ribbed mussel). In addition, serotonin was assayed in the ventricles, auricles and heart-associated tissues in A. californica, M. mercenaria, H. multirugosus, and G. demissa with a sensitive radioenzymatic assay. Serotonin concentrations and the density of innervation were significantly higher in members of the subclass Heterodonta compared to the subclass Pteriomorpha. Serotonin immunoreactivity was observed in all species surveyed except G. demissa, which also contained relatively low concentrations of serotonin. Varicose fibers presumably corresponding to release sites were localized in the ventricles, auricles, and the auricular-ventricular valves. We hypothesize that in the species where serotonin-immunoreactive fibers are present, serotonin serves to modulate cardiac myogenic activity. The significance of the observed distribution and concentration of serotonin to the physiological effects of serotonin on cardiac function in these species is discussed. PMID- 1423511 TI - Species differences in the immunoreactive patterns of calcitonin gene-related peptide in the pancreas. AB - In the pancreas, calcitonin gene-related peptide (CGRP) immunoreactivity has been described in nerve fibers and in distinct types of islet cells. This unique, apparently species-specific cell-type expression prompted the present investigation to clarify further the pattern of CGRP immunoreactivity in different mammalian species (i.e., different strains of rats, mice, guinea pigs, rabbits, cats, dogs, pigs, and humans) commonly used for functional and anatomical studies of the pancreas by means of immunohistochemistry using three different CGRP antibodies. In each species, CGRP-immunoreactive neurites innervate the exocrine and endocrine compartments, the vasculature, and the intrapancreatic ganglia, where they form dense networks encircling unstained cell bodies. The only exception is the pig pancreas, where the islets appear to be devoid of immunoreactive fibers. The overall density of immunoreactive pancreatic axons in different species is as follows: rat, mouse, and rabbit greater than guinea pig greater than or equal to pig and cat much greater than dog and human. CGRP-immunoreactive endocrine cells appear to be restricted to the rat pancreas, where they form a subpopulation of somatostatin-containing D cells. In contrast, in mouse, guinea pig, cat, dog, and human pancreas, a homogeneous staining of the core of the islets, where insulin-producing B cells are located, was visualized in sections incubated with the rabbit CGRP antiserum at 4 degrees C, but not at 37 degrees C (an incubation temperature that does not affect the islet cell staining in the rat nor the fiber labeling in any species). Furthermore, the staining of islet B cells was not reproducible with all the CGRP antibodies used, all of which comparably stain nerve fibers in each species, and islet D cells in the rat. Immunoreactive islet cells were not visualized in pig and rabbit pancreas. These results are consistent with the hypothesis that the expression of CGRP in nerve fibers is a common feature of mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to the D cells of the rat pancreas. PMID- 1423512 TI - Segmental peptidergic innervation of abdominal targets in larval and adult dipteran insects revealed with an antiserum against leucokinin I. AB - An antiserum against the cockroach neuropeptide leucokinin I (LKI) was used to study peptidergic neurons and their innervation patterns in larvae and adults of three species of higher dipteran insects, the flies Drosophila melanogaster, Calliphora vomitoria, and Phormia terraenovae, as well as larvae of a primitive dipteran insect, the crane fly Phalacrocera replicata. In the larvae of the higher dipteran flies, the antiserum revealed three pairs of cells in the brain, three pairs of ventro-medial cells in the subesophageal ganglion, and seven pairs of ventro-lateral cells in the abdominal ganglia. Each of these 14 abdominal leucokinin-immunoreactive (LKIR) neurons innervates a single muscle of the abdominal body wall (muscle 8), which is known to degenerate shortly after adult emergence. Conventional electron microscopy demonstrates that this muscle is innervated by at least one axon containing clear vesicles and two axons containing dense-cored vesicles. Electron-microscopical immunocytochemistry shows that the LKIR axon is one of these two axons with dense-cored vesicles and that it forms terminals on the sarcolemma of its target muscle. The abdominal LKIR neurons appear to survive metamorphosis. In the adult fly, the efferent abdominal LKIR neurons innervate the spiracles, the heart, and neurohemal regions of the abdominal wall. In the crane fly larva, dorso-medial and ventrolateral LKIR cell bodies are located in both thoracic and abdominal ganglia of the ventral nerve cord. As in the larvae of the other flies, the abdominal ventrolateral LKIR neurons form efferent axons. However, in the crane fly larva there are two pairs of efferent LKIR neurons in each of the abdominal ganglia and their peripheral targets include neurohemal regions of the dorsal transverse nerves. An additional difference is that in the crane fly, a caudal pair of LKIR axons originating from the penultimate pair of dorso-median LKIR cells in the terminal ganglion innervate the hind-gut. PMID- 1423513 TI - Distribution of calcitonin gene-related peptide immunoreactivity in the central nervous system of the frog, Rana esculenta. AB - The distribution of calcitonin gene-related peptide (CGRP), immunoreactive structures in the central nervous system of the frog, Rana esculenta, was studied using the peroxidase immunohistochemical method. Immunoreactive perikarya were found in all major parts of the brain. In the forebrain, neurons of the septohippocampal formation, the amygdala, the ventromedial and posterocentral thalamic nuclei, and the cerebrospinal fluid contacting neurons in the diencephalic periventricular organ showed immunoreactivity. The pear-shaped neurons of the optic tectum, and perikarya of the oculomotor nucleus in the midbrain were also immunoreactive. In the hindbrain, neurons of the cranial nerve motor nuclei, neurons of the superior vestibular nucleus, giant cells of the reticular formation, and preganglionic parasympathetic neurons of the superior salivatory nucleus were stained. Motoneurons presented immunostaining also in the spinal cord. Immunoreactive fibers were shown to occur in the olfactory tract, the striatum, the tegmentum and the basis mesencephali, the descending tract of the trigeminal nerve, the solitary tract, Lissauer's tract, and the dorsal horn of spinal cord. A comparison of the distribution of CGRP immunoreactivity in the mammalian and amphibian central nervous system revealed that, in relation to the size of the brain, CGRP is more extensively distributed in the amphibian than in the mammalian limbic system. PMID- 1423514 TI - Tunicamycin, puromycin and brefeldin A influence the subcellular distribution of neuropeptides in hypothalamic magnocellular neurones of rat. AB - Magnocellular neurones in the supraoptic nuclei of normal Long Evans and homozygous Brattleboro rats were examined electron-microscopically after intracisternal injections of tunicamycin, puromycin, or brefeldin A. Moderate (50 micrograms) or high (200 micrograms) doses of tunicamycin caused the formation of electron-dense filamentous accretions in the endoplasmic reticulum (ER) cisterns of vasopressin neurones, but only the high dose of tunicamycin also caused accretions to form in the ER of some oxytocin neurones. Immunogold labelling of ultrathin sections from tunicamycin-treated rats revealed that, in about 5% of vasopressin neurones, the accretions could be immunogold-labelled for vasopressin and its associated neurophysin. However, in the majority of vasopressin neurones, the sections required trypsinisation before immunolabelling of the accretions could be detected. Small accretions in the ER of oxytocin neurones did not label for oxytocin or its neurophysin without prior trypsinisation, whereas larger accretions in other oxytocin cells could be labelled without prior trypsin treatment. Administration of puromycin resulted in the formation of small ER accretions in both vasopressin and oxytocin neurones. These accretions were immunolabelled with antisera, respectively, to vasopressin and oxytocin, but neurophysin-immunoreactivity was in most cases absent and was not revealed by treatment with trypsin, suggesting that neurophysin-immunoreactive epitopes were absent from truncated peptides forming the accretions. Brefeldin A caused dilatation of ER cisterns and disruption of the Golgi apparatus in both oxytocin and vasopressin neurones, but did not cause accretions to form in the ER. PMID- 1423515 TI - Immunogold labelling of the cytoplasmic estradiol receptor in resting porcine endometrium. AB - Serial sections of resting porcine endometrium were analyzed with the monoclonal antibody 13H2 using goat antimouse IgG/5 nm gold as secondary reagent or with either polyclonal antibodies from goat #402 or the rat monoclonal antibody H222, both in combination with protein G/12 nm gold. A modestly higher labelling of nuclei than of cytoplasm was seen only with the monoclonal antibody H222. Polyclonal #402 and monoclonal 13H2 showed fewer attachments over nuclear than over cytoplasmic areas. The highest densities of attachment and of predominantly cytoplasmic labelling were obtained with the monoclonal antibody 13H2. The results confirm the earlier assumption of a restricted accessibility of estradiol receptor in the cytoplasm of resting cells for immunoreagents. PMID- 1423516 TI - Ultrastructural and cytochemical studies of the effects of prolactin on the lateral prostate and the seminal vesicle of the castrated guinea pig. AB - Administration of ovine prolactin to castrated guinea pigs for 2 weeks induced hypertrophy of secretory cells in the lateral prostate when compared with the castrated controls. This was accompanied by an apparent increase in the number of profiles of granular endoplasmic reticulum and well developed Golgi complexes with dilated cisternae. An increase in the number of low-contrast electron-dense secretory granules was observed 4 weeks after prolactin treatment. In the seminal vesicle, dilatation and degranulation of granular endoplasmic reticulum and an apparent decrease in the number of secretory granules were observed 4 weeks after prolactin administration. Following castration and 2 weeks after prolactin treatment, thiamine pyrophosphatase (TPPase)-reaction product was mainly confined to 1-2 trans cisternae of the Golgi complexes in secretory cells of the lateral prostate and the seminal vesicle. In both glands, a reduction of TPPase activity was observed 2 weeks following prolactin administration, and the reaction product was totally absent after prolonged treatment for 4 weeks. The present study has provided morphological evidence that prolactin is capable of stimulating the secretory function of the lateral prostate while exerting some inhibitory effects on the seminal vesicle of the castrated guinea pig. In both glands, TPPase activity, and hence the process of glycosylation was inhibited after prolactin administration. The results from radioimmunoassay indicated that the action of prolactin on these glands could be a direct effect and not mediated through testosterone. PMID- 1423517 TI - Allatostatin-immunoreactive neurons projecting to the corpora allata of adult Diploptera punctata. AB - A monoclonal antibody against allatostatin I was used to demonstrate the allatostatin-immunoreactive pathways between the brain and the corpus cardiacum corpus allatum complex in the adult cockroach Diploptera punctata. The antibody was two to three orders of magnitude more sensitive to allatostatin I than to the other four known members of the allatostatin family. Whole and sectioned brains in which immunoreactivity was localized with horseradish peroxidase-H2O2 diaminobenzidine reaction showed strongly immunoreactive cells in the pars lateralis of the brain with axons leading to and arborizing in the corpus cardiacum and the corpus allatum. Although many neurosecretory cells of the pars intercerebralis project to the corpora allata only, four strongly immunoreactive cells were evident here (two pairs on either side), and these did not project to the corpus cardiacum and corpus allatum but rather terminated within the protocerebrum in areas in which lateral cells also formed arborizations. Immunoreactivity was found in many other cells in the brain, especially in the tritocerebrum. PMID- 1423518 TI - Immuno-electron-microscopic localization of laminin and collagen type IV in normal and denervated tooth pulp of the cat. AB - The distribution of laminin-like immunoreactivity in adult normal and denervated cat mandibular tooth pulps was studied by the use of fluorescence microscopy and pre-embedding immunogold electron microscopy. Immunoreactivity to collagen IV was also assessed in order to distinguish basement membranes. In normal pulps, light microscope laminin-like immunoreactivity was strong along blood vessels and Schwann cell sheaths, and a faint immunoreactivity was seen also in the odontoblast layer. Electron microscopy confirmed the laminin-like immunoreactivity of endothelial and Schwann cell basement membranes at all pulpal levels. In the odontoblast layer and the predentine, nerve-like structures lacking basement membranes but possessing strong membrane laminin-like immunoreactivity were encountered. In addition, a clear-cut laminin-like immunoreactivity of plasma membranes of the somata and processes of odontoblasts was seen. Observations on denervated pulps as well as pulps in which nerve regeneration had taken place did not reveal any changes in the pattern of laminin immunoreactivity in basement membranes or odontoblasts. Distribution of collagen IV-like immunoreactivity was very similar to laminin-like immunoreactivity in basement membranes of blood vessels and Schwann cells, and appeared unaffected by denervation. The odontoblasts and nerve-like profiles in the odontoblast layer were devoid of collagen IV-like immunoreactivity. We propose that odontoblast associated laminin could be of significance as guidance for regenerating terminal pulpal nerve fibers to appropriate targets. PMID- 1423519 TI - The cytoarchitecture of the medial layer in rat thoracic aorta: a scanning electron-microscopic study. AB - The cytoarchitecture of the medial layer of rat thoracic aorta was examined by scanning electron microscopy after removal of the connective tissue. The outermost lamella showed a lattice-like structure of muscle bundles of closely apposed smooth muscle cells (SMCs), whereas the inner lamellae consisted of more or-less continuous muscle sheets of vaguely defined subgroups of parallel SMCs. Longitudinal rows of ridges ran along the adventitial surface of these muscle bundles and sheets. The SMCs of the outermost lamella, were 5.1 microns wide, and varied in shape, whereas those of the inner lamellae, were 52.7 microns long, 2.6 microns wide and 4.1 microns thick, and were elongated, spindle-shaped cells with serrated outlines. These latter SMCs extended obliquely, and partially overlapped each other. The surface of the SMCs in the outermost lamella exhibited a rugged texture, with nodular protrusions and oblique and longitudinal laminar folds, while the inner lamellar cells showed longitudinal laminar folds and finger-like processes on both sides of the ridges, pointing in opposite directions to the ridges. The angle of deviation from the transverse axis of the vessel, of the muscle bundles and subgroups in the outermost lamella, was 33.6 degrees, in the second and third lamellae, 22.5 degrees, and in the innermost lamellae, 12.8 degrees. The mean angle of the muscle bundle and subgroup arrangement, with respect to the long axis of the vessel, however, was basically 90 degrees in all lamellae. PMID- 1423520 TI - Differentiation of human skeletal muscle cells in culture: maturation as indicated by titin and desmin striation. AB - This report describes a phenotyping study of differentiating human skeletal muscle cells in tissue culture. Satellite cells (adult myoblasts), isolated from biopsy material, showed a proliferative behaviour in high-nutrition medium, but fused to form myotubes when grown in low-nutrition medium. The expression and structural organization of the intermediate filament proteins desmin and vimentin as well as the sarcomeric constituents alpha-actin, alpha-actinin, nebulin, myosin and especially titin during myofibrillogenesis in vitro, were studied by means of indirect immunofluorescence assays. The proliferating myoblasts contained both desmin and vimentin, alpha-actinin and the filamentous form of actin. Shortly after the change of medium, expression of titin, sarcomeric myosin and skeletal muscle alpha-actin was found in mononuclear cells in a diffuse, filamentous (titin, myosin, alpha-actin) or punctate (titin, myosin) pattern. Four to 10 days after the medium change, mature myotubes showed desmin, titin, alpha-actinin, nebulin, sarcomeric myosin and actin cross-striations, while vimentin was no longer detected. We conclude that human skeletal muscle cell cultures are an appropriate model system to study the molecular basis of myofibrillogenesis. Especially the presence of desmin in a striated fashion points to a high degree of maturation of the muscle cell cultures. PMID- 1423521 TI - Evidence for the coexistence of serotonin and calcitonin gene-related peptide at the subcellular level in neuroepithelial bodies in the lung of a marsupial, Isoodon macrourus. AB - The coexistence of serotonin and calcitonin gene-related peptide (CGRP) in neuroepithelial bodies of the bandicoot, Isoodon macrourus, has been examined using immunocytochemistry at the light- and electron-microscope levels. The avidin-biotin technique of antigen localisation was used initially to identify serotonin-like and CGRP-like immunoreactivity (-LI). Serotonin-LI and CGRP-LI were found in neuroepithelial cells in the lungs of 30-day-old bandicoots. CGRP LI could also be demonstrated in nerve fibres associated with some neuroepithelial bodies. The protein A-gold technique of antigen localisation was used to label neuroepithelial cells and nerve fibres at the subcellular level. Serotonin-LI and CGRP-LI were observed in the same dense-cored vesicles of most neuroepithelial cells; however, some neuroepithelial cells were shown to possess serotonin-LI without CGRP-LI. Nerve fibres immediately adjacent to neuroepithelial bodies exhibited mainly CGRP-LI. These results show that serotonin-LI and CGRP-LI are present in neuroepithelial cells of the bandicoot in the same secretory vesicles. This pattern of co-localisation may reflect co ordinated or synergistic actions of these two neuroactive substances. PMID- 1423522 TI - Activity labeling patterns in the medulla of Drosophila melanogaster caused by motion stimuli. AB - We quantitatively describe 2-deoxyglucose (2-DG) neuronal activity labeling patterns in the first and second visual neuropil regions of the Drosophila brain, the lamina and the medulla. Careful evaluation of activity patterns resulting from large-field motion stimulation shows that the stimulus-specific bands in the medulla correspond well to the layers found in a quantitative analysis of Golgi impregnated columnar neurons. A systematic analysis of autoradiograms of different intensities reveals a hierarchy of labeling in the medulla. Under certain conditions, only neurons of the lamina are labeled. Their characteristic terminals in the medulla are used to differentiate among the involved lamina monopolar cell types. The 2-DG banding pattern in the medulla marks layers M1 and M5, the input layers of pathway p1 (the L1 pathway). Therefore, activity labeling of L1 by motion stimuli is very likely. More heavily labeled autoradiograms display activated cells also in layers M2, M9, and M10. The circuitry involved in the processing of motion information thus concentrates on pathways p1 and p2. Layers M4 and M6 of the distal medulla hardly display any label under the stimulus conditions used. The functional significance of selective activity in the medulla is discussed. PMID- 1423523 TI - Total numbers of glomeruli and individual glomerular cell types in the normal rat kidney. AB - Alterations in numbers of glomeruli and glomerular cells occur in various renal disorders. Although values for these parameters have previously been reported for several species, the estimates have often been biased due to assumptions regarding glomerular and/or nuclear size and shape. Other studies have used tedious serial-section reconstruction methods. In the present study, unbiased stereological methods were used to estimate total numbers of glomeruli and individual glomerular cell types in normal rats. The kidneys of seven adult Sprague-Dawley rats were perfused with 4% paraformaldehyde and 1% glutaraldehyde in phosphate buffer and embedded in either glycol-methacrylate (for light microscopy, LM) or Epon/Araldite (for transmission electron microscopy, TEM). Total glomerular number was estimated using an LM physical disector/fractionator combination; the total number of cells per average glomerulus was estimated using an LM optical disector/Cavalieri combination; and TEM physical disectors were used to count individual cell types. The normal rat kidney was found to contain 31,764 +/- 3667 (mean +/- SD) glomeruli. An average glomerulus contained 674 +/- 129 cells, of which 181 +/- 53 were epithelial cells (podocytes), 248 +/- 53 were endothelial cells, and 245 +/- 45 were mesangial cells. An average renal corpuscle contained 117 +/- 27 parietal epithelial cells. Following sectioning and staining, less than 6.5 h was needed to obtain the above estimates for a single animal, with coefficients of variation (SD as a percent of the mean) ranging from 10% to 25%. The unbiased stereological methods used in the present study constitute an unbiased, precise and cost-efficient set of quantitative tools for assessing glomerular morphology in health and disease. PMID- 1423524 TI - Ultrastructural evidence for multiple mucous domains in frog olfactory epithelium. AB - This study showed that the olfactory mucus is a highly structured extracellular matrix. Several olfactory epithelial glycoconjugates in the frog Rana pipiens were localized ultrastructurally using rapid-freeze, freeze-substitution and post embedding (Lowicryl K11M) immunocytochemistry. Two of these conjugates were obtained from membrane preparations of olfactory cilia, the glycoproteins gp95 and olfactomedin. The other conjugates have a carbohydrate group which in the olfactory bulb appears to be mostly on neural cell-adhesion molecules (N-CAMs); in the olfactory epithelium this carbohydrate is present on more molecules. Localization of the latter conjugates was determined with monoclonal antibodies 9 OE and 5-OE. Ultrastructurally all antigens localized in secretory granules of apical regions of frog olfactory supporting cells and in the mucus overlying the epithelial surface, where they all had different, but partly overlapping, distributions. Monoclonal antibody 18.1, to gp95, labeled the mucus throughout, whereas poly- and monoclonal anti-olfactomedin labeled a deep mucous layer surrounding dendritic endings, proximal parts of cilia, and supporting cell microvilli. Labeling was absent in the superficial mucous layer, which contained the distal parts of the olfactory cilia. Monoclonal antibody 9-OE labeled rather distinct areas of mucus. These areas sometimes surrounded dendritic endings and olfactory cilia. Monoclonal antibody 5-OE labeled membranes of dendritic endings and cilia, and their glycocalyces, and also dendritic membranes. PMID- 1423525 TI - Quantitative changes in the frequency and distribution of the C-cell population in the rat thyroid gland with age. AB - The development of calcitonin cells (C-cells) was investigated in rat thyroid glands from birth to 120 days, using an immunoperoxidase technique and a point counting method. The proportion of C-cells to follicular cells was 4.5% on the day of birth and increased progressively to 10.4% by 120 days. The highest density of C-cells was noted in the mid-region of the lobes along a longitudinal axis. The caudal and cephalic regions of the lobes contained smaller numbers of C cells. The C-cells tended to be more numerous in the posterior aspects of the lobes. Although the numbers of C-cells in 120-day-old animal were markedly increased as compared to animals at the time of birth, the cell distributions within the glands were similar at all ages. PMID- 1423527 TI - Current bibliography of cell calcium prepared: by the University of Sheffield Biomedical Information Service. PMID- 1423526 TI - Immunohistochemical localization of the eosinophil major basic protein in the uterus horn and cervix of the rat at term and after parturition. AB - Distribution of the eosinophil major basic protein (MBP) was studied in the rat uterus horn and cervix by means of immunohistochemistry using an antiserum raised against rat MBP. Various hormonal contexts were investigated: pre- and post parturition, the estrous cycle, and ovariectomy followed by hormonal treatment or without treatment. MBP was detectable in the cervix as early as 12 h post-partum, appearing in the stroma close to the myometrium. The MBP had spread throughout the stroma toward the luminal epithelium after a few days. In contrast, no MBP was seen in sections of the corresponding pre- and post-partum uteri and in the pre-partum cervix. In cycling rats, MBP was distributed equally in the cervix and uterus and was more abundant during proestrus and estrus. In ovariectomized rats subsequently treated with progesterone, no MBP was detected in the cervix or uterus. In the cervix of ovariectomized rats treated with estradiol, MBP first appeared in the muscle layer situated between the two cervical lumina and then reached the stroma; within a few days only the stroma was stained. Inversely, in the uterus MBP-staining first appeared in the stroma. In conclusion, analysis of the distribution of MBP in rat uterus revealed a marked difference in the response of the cervix and horn to a hormonal environment. PMID- 1423528 TI - A novel principle for quantitation of fast intracellular calcium changes using Fura-2 and a modified image processing system--applications in studies of neutrophil motility and phagocytosis. AB - A new principle is described for imaging intracellular free calcium [Ca2+]i changes in single, living cells utilizing the fluorescent probe Fura-2. It is based upon video color mixing in real time and allows high-speed visualization, at maximum image resolution, of [Ca2+]i changes without digital image ratioing. The epifluorescence images produced by 340 and 380 nm excitations are stored in two memory buffers of a personal computer-based image processing system. Two video signals are generated independently from each buffer and connected to the red and green inputs of a video display. An image is this way created, in which [Ca2+]i shows up as a specific hue, whereas changes in dye concentration, light intensity, cell thickness show up as variations in brightness of the imaged cells. The method has advantages over conventional ratio imaging, notably simplicity and speed, since no calculations are made. Yet it can be combined with traditional digital image processing. The imaging technique allows monitoring of [Ca2+]i changes in rapidly moving cells, like neutrophils. It is demonstrated that during random locomotion on serum-coated glass surfaces, [Ca2+]i levels appeared to oscillate and that the frequency of the oscillations are related to locomotive activity. Furthermore, in Ca2+ free medium, the cells continue to move and phagocytose in the presence of Ca2+ ionophore (ionomycin) and 2 mM EGTA. In the presence of 1 mM extracellular Ca2+, ionomycin-treated cells were not able to move or phagocytose. PMID- 1423529 TI - Thapsigargin reveals evidence for fMLP-insensitive calcium pools in human leukocytes. AB - To investigate the relationship between different intracellular Ca2+ pools, cytosolic free calcium ([Ca2+]i) was surveyed by means of a Fura-2 fluorescence ratio method on single isolated human leukocytes. Both monocytes and neutrophilic granulocytes (PMN) displayed long lasting spontaneous [Ca2+]i transient changes (1-2 min). In PMN stimulated with the bacterial peptide fMLP we observed transients with shorter duration (10-30 s) and smaller amplitude often superimposed on the long lasting transients. The time course of changes in [Ca2+]i was recorded in a large number (149) of single leukocytes prestimulated for 5 min with fMLP and then challenged with thapsigargin (a blocker of Ca2+ uptake in intracellular pools). Statistical analysis of [Ca2+]i responses revealed that fMLP-sensitive pools contributed to the long lasting [Ca2+]i transients seen in both leukocyte types. However, the existence of fMLP insensitive calcium pools may explain the superimposed transients seen in PMN. Thapsigargin was also added together with EGTA (to impede contribution from extracellular Ca2+) to 198 fMLP prestimulated and 153 unstimulated PMN. Based on Ca2+ registrations in these cells and a mathematical model (supposing two separate first order responses) the amount of Ca2+ stored in the various pools and their release kinetics were estimated. The results indicate that fMLP insensitive calcium pools exist in PMN but not in monocytes. Since the digital imaging technique also depicts cellular motility, an additional finding was that the leukocyte's ability to sequestrate the Ca2+ from the cytosol seemed important to locomotion. PMID- 1423530 TI - Mechanically induced electrical and intracellular calcium responses in normal and cancerous mammary cells. AB - Mechanically induced channel activities and increase of intracellular calcium ([Ca2+]i) in normal and cancerous murine mammary cells (MMT 060562) were investigated using the patch clamp technique and Fura-2 fluorescence. Both cell types showed similar properties. Upon mechanical stimulation, activation of the Ca(2+)-dependent K+ channel or outward membrane current was recorded in cells which were several cells distant from the stimulated cell. Mechanical stimulation also induced an increase of [Ca2+]i in the touched cell, and this increase of [Ca2+]i spread to the surrounding cells. The [Ca2+]i signal travelled a distance of 100-200 microns within 20-40 s and then diminished. The presence of cell-to cell communication between adjacent mammary cells through gap junction was indicated by injection of lucifer yellow and measurements of electrical coupling (coupling constant = 0.2-0.3). The mechanically induced increase of the [Ca2+]i signal spread to adjacent cells even when the stimulated cell had no physical contact with them. In the absence of fluid movement, the pattern of the spread of the [Ca2+]i signal was a concentric circle. However, in the presence of fluid movement, the pattern changed to elongate to the direction of the flow. These findings suggested that a certain factor was released from the mechanically stimulated cell to the extracellular space, and this factor induces the increase of [Ca2+]i in surrounding cells. PMID- 1423531 TI - The effects of halothane and isoflurane on intracellular Ca2+ regulation in cultured cells with characteristics of vascular smooth muscle. AB - The Ca(2+)-sensitive photoprotein aequorin was used to monitor changes in intracellular [Ca2+] within cultured cells with characteristics of vascular smooth muscle. Two cell lines were investigated: they were A10 cells, which are transformed cells originally derived from rat aorta, and BC3H1 cells obtained from mouse brain neoplasm. Transient increases in intracellular [Ca2+] were induced following exposure to two different volatile anaesthetics (halothane and isoflurane) and various vasoactive substances (acetylcholine, endothelin, histamine, serotonin and vasopressin). The amplitude of the transients induced by isoflurane were more dependent on the presence of extracellular Ca2+ than those induced by halothane, thus the modes and/or locations of action of these two anesthetics are somewhat different. The response of the two cell lines to the vasoactive substances are unique. Receptor activated changes in [Ca2+]i by various agonists were diminished in the presence and absence of either anesthetic. These data suggest that, although the receptor populations within each cell line were slightly different, the prior application of a volatile anesthetic in a clinically-relevant dose induced a transient increase in [Ca2+]i that could subsequently diminish agonist responses. PMID- 1423532 TI - Transient but not oscillating component of the calcium mobilizing response to gonadotropin-releasing hormone depends on calcium influx in pituitary gonadotrophs. AB - Gonadotropin-releasing hormone (GnRH)-stimulated changes in the cytosolic free Ca2+ concentration ([Ca2+]i) were studied in gonadotrophs cultured from 3-week ovariectomized rat pituitaries. One animal was used per cell preparation. [Ca2+]i was monitored in individual gonadotrophs by dual emission microspectrofluorimetry, using Indo-1 as the intracellular fluorescent Ca2+ probe. A short stimulation with GnRH evoked a complex concentration-dependent Ca2+ response in individual gonadotrophs. 0.1-1 nM GnRH triggered a series of sinusoidal-like [Ca2+]i oscillations superimposed upon a modest slow [Ca2+]i rise -the oscillating response mode--while 10-100 nM GnRH caused a biphasic increase in [Ca2+]i consisting of a monophasic transient and oscillations--the transient/oscillating response mode. Despite the consistency of Ca2+ responses, an inter-preparation heterogeneity of [Ca2+]i oscillations frequency was noticed. Moreover, we observed that, within a given cell preparation, the frequency of [Ca2+]i oscillations was independent of GnRH concentration whereas both peak [Ca2+]i and area under the [Ca2+]i versus time curve were concentration dependent. Thus, in gonadotrophs, the presence of the GnRH signal would lead to [Ca2+]i oscillations, while the amplitude of the [Ca2+]i responses would code for the concentration of agonist. Both transient and oscillating components of GnRH responses depended on releasing activity of Ca(2+)-sequestering pools in as much as GnRH responses were unaffected by brief removal of external Ca2+, but suppressed by chelating intracellular free Ca2+ with BAPTA. However, prolonged exposure to a Ca(2+)-free medium suppressed the transient component while leaving the oscillating component unaffected. We therefore propose that gonadotrophs employ Ca(2+)-sequestering pools, whose maintenance depends on a slow Ca(2+) entry, to give an amplitude-coded Ca2+ rise in response to a short GnRH stimulation. PMID- 1423533 TI - [Multilocus enzyme electrophoretic types of Neisseria meningitidis serogroup B and their epidemiologic significances]. AB - In order to expand the epidemiologic relationships between the strains of Neisseria meningitidis serogroup B isolated from patients and carriers, 57 cases and 45 carrier isolates were collected in 11 provinces and 2 municipalities of China since the 1970s and their multilocus enzyme electrophoretic types and clonal population structures were studied by multilocus enzyme electrophoresis. It was primarily found that the above strains could be divided into 69 electrophoretic types (ET) and 13 clones. Among others, the clone I was the most important one, because the clone I represented 63.7% of all strains tested and 77.2% of the case isolates and its district distributions were quite wide since the 1970s. In addition, it was an obvious tendency that more and more of the case isolates gathered up the clone I since 1984 and the predominant ETs also occurred in the complex ET 1 and ET 24 of the clone I. As compared with the case isolates, the above carrier isolates displayed more heterogenetic types. Only 40% of all carrier isolates belonged to the above clone I and predominant ETs. PMID- 1423534 TI - [A study on the relationship between maximal titers of anti-HBs antibodies and persistence of protective level after vaccination]. AB - 300 recipients with negative for HBsAg anti-HBs, anti-HBc were vaccinated by 3 kinds of hepatitis B vaccine at 0, 1, 6 months. 266 students with maximal titers of anti-HBs detected after the 3rd immunization were divided into 4 groups: 10 100, 101-500, 501-1,000, > 1000 mlU/ml. A study on the relationship between maximal titers of anti-HBs and the protective time was carried out. The results showed that in the 1st group the titers of anti-HBs of 52.6%, 84.2% and 94.7% recipients decreased to or below 10 mIU/ml when detected one, two and three years after vaccination respectively; the titers of 5.2%, 31% and 56.9% decreased to or below 10 mIU/ml when detected. 1, 2 and 3 years after vaccination respectively in the 2nd group, while the titers of only 0.7% recipients decreased to or below 10 mIU/ml when detected 3 years after vaccination in the 1st group. The decreasing rate of titers of Anti-HBs was similar in 4 groups. The titers of anti-HBs were 90% reduction after 1st immunization in the first 24 months. Then the decreasing rate became slower. Therefore, we suggested that peoples should be revaccinated according to their maximal titers of anti-HBs after completed course of vaccination. PMID- 1423535 TI - [A study on measles vaccination rate and its antibody level in children aged 12 24 months in Guangxi, 1989]. AB - This report described the measles vaccination rate (MVR) as well as its HI antibodies of 1842 children aged from 12 to 24 months. The MVR was 99.57% but HI positive rate was only 83.50%. HI of 298 target children still remained negative. Among them, 6 children were unvaccinated and others vaccinated. The HI negative rate reached 16.50% The HI positive rate was higher in the target children who lived in the area with convenient transportation and relatively low atmospheric temperature, and who received measles vaccine at the age of 8 months or more. Otherwise, the HI positive rate was lower. So some suggestions were proposed that the vaccination season, age of vaccine, increasing vaccine dosage should be considered carefully before measles vaccination session had arranged. PMID- 1423536 TI - [A study on the interference between smooth and rough species of brucella in mice]. AB - Smooth-B. abortus 104M. B.melitensis Rev-1 and B.suis S2 mixed with rough-B.canis RM 6/66 respectively were injected into mice. The results demonstrated that s species of Brucella suppressed R-species of B.canis RM6/66 in mice. The epidemiological phenomenon that R-species of Brucella were difficulty isolated in focus of s-species should be explained on the bases of the study. PMID- 1423537 TI - [Use of Cox's model in long-term survival analysis of cerebrovascular disease]. AB - A long-term survival study on 885 cases of cerebrovascular disease was carried out. The results showed that after follow-up for 3, 5, and 8 years, the survival rates were 86.98%, 75.70% and 64.26% respectively, and all were lower obviously than that of the general population in the same district. The results of Cox's model analysis showed that recurrence, hypertension and age were the risk factors influencing the long-term survival of cerebrovascular disease, and the relative risks were 3.29, 2.17 and 1.65 respectively. PMID- 1423538 TI - [Cluster and multiple regression analysis of leptospirosis epidemic factors]. AB - Ten-year surveillance of Rice-field-typed leptospirosis was carried out in high infected foci. Twenty two parameters of epidemic data were divided into 3 categories and cluster-analyzed. 5 typical variables were selected for multiple regression equation. The equation contained four factors, i.e. rodents density, carriage rates of main animal hosts, GMT of population antibody against leptospira and quantity of rainfall in August. The expected morbidity of leptospirosis calculated by the equation were roughly identical to the real morbidity. PMID- 1423539 TI - [A prospective study on the relationship between abnormal pregnant outcome and Toxoplasma gondii infection]. AB - 2821 pregnant women were divided into three groups according to the phenomena of Toxoplasma gondii infection, and the pregnancy outcomes were followed up. Results show that the total incidence rates of spontaneous abortion, premature birth, still birth and congenital defects are 0.67%, 3.47%, 0.85% and 0.96% respectively. These four rates in the group serodiagnosed as recently or actively infected are significantly higher than that diagnosed as no evidence of infections and the relative risk estimates (ORmh) are 7.38, 3.52, 8.68 and 9.44 respectively. Differences of the four rates between group diagnosed as past infection and that of no evidence of infection are not statistically significant. Analysis between the time of serodiagnosis and the incidence of abnormal pregnant outcome shows that congenital defects is statistically related with infection in the first trimester of gestation. PMID- 1423540 TI - [Hygienic epidemiological assessment of electrodialysis drinking water]. AB - It is first reported the hygienic epidemiological assessment of electrodialysis drinking water with multidiscipline methods including environmental epidemiology, toxicology, chemistry and clinical medicine. The results showed that the occurrence of malignant tumours in residents drinking electrodialysis water did not directly associate with their drinking water, we also did not find that there was any influence of electrodialysis water on residents' liver and gastrointestinal function, and the rate of thyroid enlargement, prevalence rates of dental fluorosis and dental caries as well as the level of saliva lysozyme in children. However, the morbidity rate of hypertension in the residents drinking electrodialysis water was higher than that in those drinking non-electrodialysis water. PMID- 1423541 TI - [The economic loss of poliomyelitis outbreak in Pi County and economic beneficial analysis on EPI]. AB - In 1989, there was a poliomyelitis outbreak in Pi county, Jiangsu province. The total case number was 597 in which 52 died. It caused the patients' families and national economic loss 2,713,107.32 yuan and lessened creating value of 18,583,942.35 yuan for the country. The outbreak was mainly caused by the fact that many children did not set vaccination card, missed vaccination chance and lacked in immunity to polio. So the ratio of cost-benefit will be expected to reach 1:6.85, and the net benefit of 2,317,268.16 yuan can be gained if the task of EPI is implemented well to avoid the occurrence of outbreak. PMID- 1423542 TI - [The monitor method of immunization coverage]. AB - A comprehensive monitor method of immunization coverage is suggested to be applied to the expanded program on immunization. The routine coverage reporting system should be set up combined with surveys in selected townships. The criteria for doing survey is expressed in the flow chart. Two sampling methods are presented based on the principle of lot quality assurance sampling (LQAS) and coverage rate could be estimated after the surveys. PMID- 1423543 TI - [Chlamydia trachomatis and urogenital diseases]. PMID- 1423544 TI - Stress and psychological disorders in Zimbabwe: a report on patients seen in private practice. AB - This report is based on the analysis of 326 case files of patients that I saw in part-time private practice over a period of five years. The aim of the investigation was to establish the stressful life events that are associated with psychological disorder. Thirteen categories of stressful events were identified. Statistical analyses revealed that these stresses were significantly associated with a number of demographic variables. PMID- 1423545 TI - The effects of established and gestational diabetes on pregnancy outcome at Harare Maternity Hospital. AB - A study was carried out to determine the effect of established and gestational diabetes on pregnancy outcome over a period of two years at Harare Maternity Hospital, Harare, Zimbabwe. During the period, 51 patients with established diabetes mellitus and 70 patients with gestational diabetes were treated. The perinatal mortality was higher among this group (124 per 1,000) compared with the rest of the total hospital population (44 per 1,000) who delivered during the same period. PMID- 1423546 TI - Reference values for glucose tolerance test in the urban Zimbabwean pregnant woman. AB - A 50 g oral glucose tolerance test (OGTT) was performed on normal pregnant urban Zimbabwean women at 26-28 weeks (n = 65) and 36-40 weeks (n = 72) gestation. Women with factors predisposing to impaired glucose tolerance were excluded. The fasting, one hour and two hours values were compared to the North American standards as proposed by O'Sullivan and Mahan which are currently in use. The mean fasting levels were significantly higher and those at one and two hours significantly lower than the standards. The study also failed to demonstrate impairment of glucose tolerance with advancing gestation. These may have implications in the screening for impaired glucose tolerance in our African population. PMID- 1423547 TI - Cancer of the oesophagus in Zimbabwe. AB - Data for oesophageal cancers were requested from the Cancer Registry of Zimbabwe for the three years 1986-1988. There were 437 cases notified compared with 783 cases recorded in the Government's Statistical returns. There was a ratio of 6.9 males to one female accounting for 13.2 pc of all reported cancers in males and 1.7 pc of cancers in females. Prevalence increased with age to a rate of around 83 per hundred thousand in men aged 55 and older and 19 per hundred thousand in women over 65 years old. Notifications are only received from the Central Hospitals in Harare and Bulawayo. Addresses were not available for 31 pc of patients so that geographical variations could not be determined accurately. However, higher rates occurred in Harare and in the Mashonaland Provinces. It is recommended that cancer notifications should be obtained from all Government, Mission and Private hospitals in Zimbabwe. PMID- 1423548 TI - Skin sensitivity patterns to inhalant allergens in Nigerian asthmatic patients. AB - The pattern of skin sensitivity response to inhalant allergens in 746 Nigerian asthmatics and 92 normal controls tested over 10 years period is reported. Significant differences in reactions were observed in seven of the 16 allergens routinely used in the study. House dust mite--dermatophagoides pteronyssinus- gave the highest incidence of positive skin reaction in 58 pc asthmatics and 4.3 pc controls (P = 0.002). Other significant allergens were house dust, 51.7 pc, feathers; 24.4 pc, dog hair, 12.9 pc, cat fur, 11.9 pc; grass pollen, 6.8 pc and flower pollen, 6.3 pc. More males than females reacted to most of the allergens but this was statistically significant only for feathers (p less than 0.02). There was good apparent association between history and skin sensitivity for most allergens. Eighty-two comma three percent of patients with a positive skin test to D. pteronyssinus gave a positive history of dust induced asthmatic attacks. Similar results were obtained for pollens; (grass, 86.3 pc, flower, 83 pc and feathers 57.7 pc.) The association was, however, poor in respect of animal allergens (dog, 30.6 pc; cat, 36 pc). From the findings of this study, there may be no point in routinely testing patients with a battery of allergens most of which may have no importance in the tropics. Attempts are, however, underway to incorporate local substances in skin testing materials. It is hoped that the results of this study will assist doctors who may not have access to skin test reagents in management of their asthmatic patients. PMID- 1423549 TI - Evaluation of Pathstrips for semi-quantitative determination of proteinuria. AB - Pathstrips semi-quantitatively determine concentration of protein in urine. The Pathstrip has a protein detection limit of 0.3 g/l and is stable at high temperature (40 degrees Celsius). Pathstrip was found favourably comparable to currently available Reagent strips for protein detection in urine (e.g. Ames Reagent strips). The Pathstrip is easy to use and add in the range of reagent strips for detection of urine protein as a test near the patient. No significant difference was obtained in semi-quantitation of urine proteins between Pathstrips and other currently available Reagent strips (e.g. Ames and BM Test). PMID- 1423550 TI - The diminishing medical population (and other medical professionals) PMID- 1423551 TI - Carcinoma of the cervix and cervical cytology--short epidemiological review. AB - Carcinoma of the cervix is an important disease of well-documented epidemiology but uncertain cause. It causes appreciable morbidity and mortality in all countries, including Zimbabwe, with a significant load on curative services. Epidemiology and the role of cytology are reviewed. Cytology screening programmes have suffered from an inability to cover whole populations, particularly less affluent and/or socially disadvantaged groups, which are most at risk. Despite this difficulty, the magnitude of the problem makes it necessary to continue its study. In particular, efforts are needed in developing countries to study incidence, to better define high risk groups and to devise economical ways of detecting more cases in the earlier stages. PMID- 1423552 TI - Adult intussusception in northern Nigeria: a changing disease? AB - Intussusception in the tropics and sub-tropics had always been regarded as mainly a disease of adults. This paper reports on both a decrease in frequency of the disease in the adult as well as a reduction in the frequency of large bowel involvement. Sixteen adults were treated for intussusception in Ahmadu Bello University Teaching Hospital, Zaria in 10 years. The correct diagnosis was made in one patient prior to operation. Eight intussusceptions were of small intestinal origin and eight were colonic. One patient in the enteric group and three in the colonic group had benign tumours. One colonic tumour was malignant. Eleven intussusceptions were "idiopathic". Four patients in the enteric group had resection; one for neoplasm and three for irreducibility. Four patients in the colonic group had resection, all for neoplasm. Morbidity was minimal and there was no death. A treatment strategy at variance with that advocated in the Western world is suggested. PMID- 1423553 TI - Colostomy closure: basic errors. PMID- 1423554 TI - TCD and headache. PMID- 1423555 TI - Arterial head pain. PMID- 1423556 TI - Headache in ischemic cerebrovascular disease. Part I: Clinical features. AB - Headache is a common, although under-emphasized, feature of ischemic cerebrovascular disease. In this review, we summarize the literature on the clinical features of headache in ischemic cerebrovascular disease (Part I) and elaborate upon the underlying mechanisms of the head pain (Part II--December issue). PMID- 1423557 TI - Reduction of calcitonin gene-related peptide in jugular blood following electrical stimulation of rat greater occipital nerve. AB - Although it is known that pain in the forehead may be induced by neck abnormalities, the actual neck-head connections responsible for development of pain in trigeminal areas are poorly understood. Vasoactive neuropeptides released from sensory fibres, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been considered as important elements in headache pathophysiology. The levels of CGRP-like immunoreactivity (LI) were measured bilaterally in the jugular blood (52 rats) and intraocular aspirates (66 rats) following electrical stimulation of the left greater occipital nerve, and in the jugular blood of 13 control animals. One-third of the stimulated rats had varying combinations of conjunctival injection, tearing, diminished eye aperture and miosis or mydriasis on the stimulated side. The other two-thirds exhibited no ocular signs. Significantly lower levels of CGRP-LI were present in the jugular blood on the stimulated side in comparison with control rats. There was comparatively lower CGRP-LI on the non-stimulated side as well, but to a lesser extent. Significant differences between the stimulated and the non-stimulated side were present, particularly in the tearing/diminished eye cleft group. It is proposed that stimulation of the rat GON inhibits the trigeminal system (reduction of CGRP-LI) and possibly activates parasympathetic fibres (ocular changes). PMID- 1423558 TI - The influence of acetazolamide on cerebral low-flow regions in migraine--an interictal 99mTc-HMPAO SPECT study. AB - Acetazolamide, a carbonic anhydrase inhibitor, has proved to be useful in the assessment of "vasodilatory capacity" in cerebrovascular disease. To obtain further information on the nature of interictal low-flow regions in migraine, we reinvestigated 20 asymptomatic patients suffering from migraine with aura (n = 15) or without aura (n = 5) and who had either minor (n = 12) or marked (n = 8) regional hypoperfusion when examined in a previous 99mTc-HMPAO SPECT investigation. These patients received acetazolamide IV prior to tracer application. In 14/20 cases regional hypoperfusion resolved. Three patients with migraine with aura had less pronounced regional hypoperfusion compared to baseline. No change in baseline hypoperfusion was detectable in three older patients. No further decreases in flow were measured. In contrast to patients with cerebrovascular ischemia, in whom acetazolamide usually enhances low-flow regions, vasodilatory capacity appears intact in most migraine patients with interictal regional hypoperfusion. Thus, the "acetazolamide test" might be useful in the differential diagnosis of migraine with aura from transient cerebrovascular ischemia. PMID- 1423559 TI - The blink reflex in migraine. AB - The blink reflex is an objective and useful method to study the trigeminal system. It was recorded in 43 migraine patients and the findings compared with those of 31 healthy controls. The latencies of the R1 component were in the normal range in both groups. The R2 latencies ranged between 30 and 32 ms in the control group. In contrast, more than half of the patients with migraine had R2 latencies between 32 and 35 ms in the migraine group. Some migraine patients had latencies above 35 ms. The R2 latency was statistically significantly different between controls and migraineurs (p < 0.0001). Our findings indicate that trigeminal afferents and/or polysynaptic pathway in brainstem may be altered in migraine. PMID- 1423560 TI - Transcranial Doppler ultrasonic features in episodic tension-type headache. AB - In a pilot study we used transcranial Doppler ultrasound (TCD) to measure cerebral blood flow velocities in 21 headache-free episodic tension-type headache sufferers and in the same number of age- and sex-matched control subjects. We found increased blood flow velocities in the anterior, middle and posterior cerebral arteries and a decreased pulsality index in the middle and posterior cerebral arteries in tension-type headache sufferers compared to controls. Vascular bruits were significantly more frequent in the basal cerebral arteries of the patients compared to controls. There were no significant asymmetries of blood flow velocities in corresponding arteries. The findings suggest a multifactorial pathogenesis in episodic tension-type headache including vascular abnormalities. PMID- 1423561 TI - The optimal length of headache recording in juvenile migraine patients. AB - The representativeness of headache recording periods of one, two, three, four and five weeks for juvenile migraine was examined in 41 juvenile patients (suffering from migraine attacks at least twice a month). At pre-treatment and at follow-up, on average a three-week recording period was found to be adequate. On the basis of these findings a longer data-collection period is recommended for juvenile migraineurs than for adult migraine patients at follow-up. PMID- 1423562 TI - Headache and Chiari type I malformation: occurrence in female monozygotic twins and first-degree relatives. AB - The Chiari type I malformation has recently been reported in three generations of a family, including female monozygotic twins. Headache was the main symptom in several family members. Various headache patterns consistent with migraine without aura, cough headache, tension headache and hypoliquorrhoeic headache were present, and different patterns might coexist in the same patient. In the twins and their mother, who all had a headache consistent with migraine without aura, there were atypical features such as occipital pain location, lack of side-shift of the pain, lack of ergotamine effect and precipitation of attacks by Valsalva like manoeuvres. The headache was significantly relieved by operation in the one twin with major herniation and the most marked headache. We suggest that in these patients the migraine-like headache mimics true migraine but that there is a causal relationship between the different headache types reported and the malformation. PMID- 1423563 TI - Pain as the only manifestation of internal carotid artery dissection. AB - Internal carotid artery dissection is a major cause of ischemic stroke in the young. Pain is the leading symptom and is associated with other focal signs such as Horner's syndrome and painful tinnitus or with signs of cerebral or retinal ischemia. We report two patients with angiographically confirmed extracranial internal carotid artery dissection presenting with cephalic pain as the only manifestation. The first patient had a diffuse headache and a latero-cervical pain lasting for 12 days, reminiscent of carotidynia. The second patient experienced an exploding headache suggestive of subarachnoid hemorrhage, which was ruled out by computed tomography of the head and cerebrospinal fluid study. These patients demonstrate that recognition of carotid artery dissection as a cause of carotidynia and headache suggestive of subarachnoid hemorrhage may permit an earlier diagnosis and possibly the prevention of a stroke through the use of anticoagulation. PMID- 1423565 TI - Platelet size and volume distribution measured by automated platelet analyzer. AB - Thirty migraine without aura patients between attacks, 10 other during a migraine without aura attack and 30 normal subjects without headache were studied for platelet size and volume distribution using a new quantitative automated hematology analyzer (Coulter STKS). Platelet histograms, platelet counts and mean platelet volume were not significantly different in the three populations. PMID- 1423564 TI - Ipsilateral cluster headache and chronic paroxysmal hemicrania: two case reports. AB - We report two patients with ipsilateral attacks of cluster headache and chronic paroxysmal hemicrania. The first patient, a 33-year-old man, started having attacks of chronic cluster headache at the age of 27. At 33, they were replaced by typical attacks of ipsilateral chronic paroxysmal hemicrania which showed a dramatic improvement with indomethacin 150 mg daily. After two days of complete remission, cluster headache attacks reappeared and persisted until verapamil, 360 mg a day, was added to indomethacin. The second patient, a 45-year-old man, first developed attacks of episodic cluster headache at the age of 35. At 44, he experienced ipsilateral typical attacks of chronic paroxysmal hemicrania, and two months later attacks of cluster headache. Under verapamil 240 mg daily, attacks of cluster headache disappeared, but those of chronic paroxysmal hemicrania increased in frequency until indomethacin 150 mg daily was added. These observations suggest a close relationship but not a similarity between cluster headache and chronic paraoxysmal hemicrania, and show the practical therapeutic interest of maintaining this distinction. PMID- 1423566 TI - A double-blind controlled study of nifedipine as an abortive treatment in acute attacks of migraine with aura. AB - Patients with migraine with aura treated each of six acute attacks with either nifedipine or vehicle administered in double-blind, randomized form. Two modes of administration were studied. Both increased the intensity of headaches compared to vehicle. We conclude that nifedipine is not useful as an abortive treatment of migraine with aura. PMID- 1423567 TI - Occipital nerve block in the management of headache and cervical pain. PMID- 1423568 TI - Chronic paroxysmal hemicrania which appears to arise from either third ventricle pathology or internal carotid artery pathology. PMID- 1423569 TI - Pressure pain detection (PPD) and tolerance (PPT) thresholds. PMID- 1423570 TI - The "coming out" of coronary balloon angioplasty. PMID- 1423571 TI - Salvage angioplasty: an alternative to high risk surgery for unstable angina? AB - This prospective, Human Subjects Committee and Ethics Committee approved investigation was performed to determine if coronary angioplasty (PTCA) might be a reasonable alternative revascularization method for unstable angina patients thought to be at high risk for operative (CABG) mortality. Between March 1990 and October 1991, thirty-four consecutive patients with medically refractory rest angina were deamed to have high risk of surgical mortality and underwent PTCA without surgical backup. Predicted operative mortality was calculated for each patient based upon the VA Surgical Risk Assessment model. Angioplasty of 52 vessels was attempted. Reduction in lumenal narrowing to < 50% and improved angiographic flow was obtained in 47 vessels. There were four complicating infarctions. One death occurred in the lab, and three patients with unsuccessful angioplasty died within 30 days of pump failure. Relief of angina occurred in 30/34. Thirty patients were discharged home. In follow-up from 1 to 12 months, there have been 2 late sudden deaths at 4 months and 9 months, 1 death from lung cancer; 4 patients have stable exertional angina; 2 are awaiting heart transplant but are pain free, and one patient who had PTCA during cardiogenic shock from acute myocardial infarction had elective coronary artery bypass surgery. There have been no late myocardial infarctions. The observed angioplasty 30-day mortality of 11.8% (95% confidence limit 1% to 22.6%) compares favorably with the predicted operative mortality of 23.8% for this group. This prospective but non randomized series supports the concept that balloon angioplasty may be a reasonable alternative to surgical intervention in some patients with unstable angina and high risk for surgery. A prospective randomized trial is warranted. PMID- 1423572 TI - Balloon catheter requirements during contemporary percutaneous transluminal coronary angioplasty. AB - In order to examine the outcome of utilizing multiple balloon catheters during the percutaneous transluminal coronary angioplasty (PTCA), 300 consecutive PTCAs were analyzed. PTCA was performed in a single lesion in 163 patients (54%), in multiple lesions in 52 patients (18%), and in multiple vessels in 85 patients (28%). A total of 488 balloon catheters were used (1.6/case, range 1-9) and in 112 cases (37%) > or = 2 catheters were used. Multiple balloon catheters were needed in 27 single lesion (17%), 24 multilesion (48%), and 61 multivessel (72%) cases (p < .05). There was no difference in the angiographic success rate in cases completed with 1 balloon catheter (238/251, 95%) compared to those requiring > or = 2 catheters (260/274, 95%). Emergency bypass was required in 5 patients (1.7%) and there were 2 deaths (0.6%). Thus, although contemporary PTCA frequently requires multiple balloon catheters for completion, success rates remain high and appear to offset the increased procedural expenses. PMID- 1423573 TI - Changing incidence and management of abrupt closure following coronary intervention in the new device era. AB - Abrupt closure of the dilated segment occurs in approximately 4 to 7% of cases following conventional percutaneous coronary angioplasty. Additional balloon angioplasty reverses roughly 40% of these closures, to yield an overall 1.6 to 3.4% rate of emergent surgery. The impact of new devices on the incidence and reversal rate of abrupt closure has not been examined. Abrupt closure occurred in 80 (4.2%) of 1,919 consecutive coronary angioplasties performed in our single center, 389 (20%) of which were performed using newer interventions (208 Palmaz Schatz stents, 170 directional coronary atherectomies, and 11 elective laser balloon angioplasties). Abrupt closure was less frequent following newer coronary interventions (1.8%) compared to standard balloon angioplasty (4.9%, P < 0.01), possibly reflecting case selection. When abrupt closure did occur, percutaneous rescue was successful in 53 (66%) patients, including 42 (53%) who were rescued using standard or perfusion balloon angioplasty, and 11 (13%) who were rescued using laser balloon balloon angioplasty after failure of additional angioplasty attempts. Medical therapy alone was used in 8 (10%), while emergent coronary bypass surgery was performed in 18 (23%), yielding an overall emergent surgery rate of 0.9%. Q-wave myocardial infarction was significantly less frequent (0.2%) following percutaneous rescue, compared to either medical therapy (25%) or emergent surgery (33%, P < 0.001). In our catheterization laboratory, use of these 3 new coronary interventional devices coincides with a trend towards a lower incidence of abrupt closure, a higher percutaneous rescue rate with reduced incidence of myocardial infarction, and a lower emergent bypass surgery rate. PMID- 1423574 TI - Coronary angioplasty of bifurcational lesions without protection of large side branches. AB - To assess the risk and clinical relevance of side branch (SB) occlusion during angioplasty (PTCA) we attempted PTCA of major branches (MB) without protection of lesion-associated large (> or = 1.8 mm) SBs in 67 patients (50 men). There were 32 patients with unstable angina and 35 with stable angina. Their mean age was 55 years (range 31-77). There were 69 SBs: 43 with severe ostium stenosis (type A); 6 with severe non ostial stenosis (type B); and 20 with no or slight nonostial stenosis (type C). PTCA of the MB was successful in all but one patient who underwent acute bypass surgery. After MB PTCA occlusion occurred in 10 SBs (7A, 1B, 2C) and was asymptomatic in 5. Recanalization and dilatation was successful in 4 out of 5 symptomatic SB occlusions. A single patient developed a non-q wave myocardial infarction. PTCA was also attempted in 21 diseased SBs and failed in one. 21 SBs remained severely stenotic and 6 occluded. During follow-up symptomatic MB restenosis occurred in 12 patients, associated with restenosis in 4 out of 6 dilated SBs. Four patients underwent bypass surgery and 8 repeat successful PTCA. The SB was redilated in 2 cases and occluded silently in one. Angiography in 16 asymptomatic patients showed moderate MB restenosis in 3 and SB occlusion in 2. At 2.2 years follow-up 60 (89%) patients were asymptomatic with a normal exercise test and/or maintained angiographic result. Angioplasty of bifurcational lesions without SB protection can be effectively performed with a low rate of complications and a favourable long-term outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423575 TI - Measurements of central blood vessels in infants and children: normal values. AB - In order to provide physicians interpreting vascular radiographic studies with normal data regarding central blood vessel size in children and to facilitate the design and adaptation of intravascular devices for pediatric use, we measured lengths and diameters of central blood vessels in 141 radiographic studies in 136 children. The diameters of the following vessels were determined: right and left internal jugular veins and common carotid arteries; the inferior vena cava and the descending thoracic aorta; right and left iliac veins; and right and left femoral veins and arteries. In addition, the lengths of the inferior vena cava and the descending aorta were also determined. Blood vessel dimensions were highly correlated with age, height, weight, and body surface area. The linear regression equations for each measured dimension against age, weight, height, and surface area are provided, along with a table of predicted vessel size as a function of age. PMID- 1423576 TI - Excimer laser ablation before autoperfusion balloon inflation: a novel therapeutic approach to high grade stenoses in vessels supplying substantial myocardium at risk. AB - The utility of a novel approach employing excimer laser ablation to form a channel for subsequent autoperfusion balloon angioplasty is presented. Two important advantages of this strategy are highlighted: (1) applicability to severe stenoses in vessels supplying substantial myocardium at risk and (2) ability to allow prolonged inflation time to minimize procedure related ischemia and optimize revascularization of the heart. We prospectively selected and studied five patients and performed excimer laser coronary angioplasty using either a 1.3 mm or 1.6 mm laser catheter followed by autoperfusion balloon dilatation. Procedural success was documented by a significant reduction in mean percent diameter stenosis from 89 +/- 4% (S.D.) to 53 +/- 4% after laser angioplasty (p < 0.0001) and subsequently to 20 +/- 4% after autoperfusion balloon angioplasty (p < 0.0001). Clinical success was attained and characterized by resolution of anginal symptoms for at least 4 weeks after hospital discharge. There were no major acute complications encountered; however, restenosis has occurred in 2 out of 5 patients. We therefore recommend this novel pre-dilation strategy with excimer laser followed by autoperfusion balloon angioplasty in selected patients with an extensive amount of myocardium at risk. PMID- 1423577 TI - Shearing of the plastic coating of a hydrophilic guide wire in a right femoropopliteal bypass graft: removal from the contralateral side. AB - The plastic coating of a hydrophilic guide wire tore off during introduction through a beveled single wall arterial entry needle in a 75 year old male. The sheared piece of coating got stuck in his femoropopliteal bypass. It was removed by means of a modified arterial filter set from the contralateral side. The technique of its removal is described. PMID- 1423578 TI - Budd-Chiari syndrome treated successfully by percutaneous transluminal balloon angioplasty: two cases followed-up for 6 years. AB - We report 2 cases of Budd-Chiari syndrome that are due to complete membranous obstruction between the junction of the inferior vena cava and the right atrium. Both cases were treated successfully by King's bioptome breakthrough followed by balloon dilatation of the membrane. The patients showed remarkable symptomatic improvement and promising hemodynamic and angiographic results immediately after the procedure and 6 years later. We conclude that balloon angioplasty is a safe and effective method for treating this rare disease in selected cases. PMID- 1423579 TI - Anomalous origin of the left coronary artery from the pulmonary artery: direct assessment of anomalous and collateral coronary flow by pulsed Doppler echocardiography. AB - We directly assessed the anomalous and collateral coronary flow profiles of a 58 year-old-man with Bland-White-Garland syndrome using pulsed Doppler echocardiography. Doppler recordings in this patient document the utility of pulsed Doppler echocardiography in the assessment of a cardiac shunt associated with a congenital coronary anomaly in an adult. PMID- 1423580 TI - Endomyocardial biopsy: advantages of adding a posterior bend to the bioptome. AB - A modification of the distal end of a flexible bioptome used for endomyocardial biopsy is described which facilitates the approach to the interventricular septum. Contact with the right ventricular free wall is avoided. PMID- 1423581 TI - Peripheral stent recovery after failed intracoronary delivery. AB - The Palmaz-Schatz stent can be successfully deployed in most patients. However, in a small percentage of instances a systemic embolism of the stent has been reported. In the present article we describe an easy and fast method of stent capture when detachment from the balloon has happened (pulling back the stent loaded balloon into the guiding catheter or femoral sheath). In this situation we propose the use of the coronary guide-wire "as a guide" to capture coaxially the lost stent. This method allows for continuing the procedure without removal of the femoral sheath. PMID- 1423582 TI - Long-tip guiding catheter: successful and safe for left coronary artery angioplasty. AB - A long-tip guiding catheter was designed for angioplasty of the left coronary artery. Principal factors of guiding catheter function were identified, and the catheter's shape was designed to utilize them efficiently. Emphasis was placed on an overbent secondary curve (150-180 degrees) for more precise catheter control. The distal tip of the catheter is 2 cm long in the 4.0 size and the primary bend is shallow, approximately 20%. A 1.5 cm long segment between the secondary and tertiary curves enhances stability and support. Catheter performance was studied during procedures on 90 patients; 89 patients underwent coronary artery angioplasty and one patient underwent diagnostic angiography. The success rate for angioplasty was 95% with no major complications. Mild pressure damping occurred in 18 patients, and mild catheter displacement from the left main coronary artery occurred in 24 patients. Catheter support was judged as excellent to very good in 82 patients. Judkins or Amplatz catheters were not required during this study. The observed disadvantages of the long-tip catheter were the risk of catheter buckling up during advancement into the left main coronary artery and, perhaps, a higher risk of pressure damping. Superselective engagement of the catheter in the left anterior descending or circumflex arteries may be a problem when the left main coronary artery is very short. This study showed the long-tip catheter to be safe and highly successful for angioplasty of the left coronary artery. PMID- 1423583 TI - Radio-opaque tipped Mullins sheath. PMID- 1423584 TI - Clinical use of disarticulated Palmaz-Schatz stents. PMID- 1423585 TI - Koch's postulates for cholesterol. PMID- 1423586 TI - TFIIB, an evolutionary link between the transcription machineries of archaebacteria and eukaryotes. PMID- 1423587 TI - Molecular signals in the interactions between plants and microbes. AB - The field of plant-microbe interactions has witnessed several recent breakthroughs, such as the molecular details of vir gene induction, identification of Nod factors, and the cloning and characterization of avr genes. Other breakthroughs, such as the cloning and characterization of R genes, appear imminent. Parallels to mammalian systems are emerging in the world of plant microbe interactions, for example, ion channels formed by Rhizobium proteins, similarities of hrp genes to pathogenicity genes of mammalian pathogens, and plant signal transduction via calcium and protein phosphorylation. We remain, however, largely ignorant of many facets of signaling in plant-microbe interactions. We know little about how microbial signals are perceived by plants or how subsequent signal transduction occurs within plant cells and are probably unaware of many of the microbe-generated signals to which plants respond or of plant-generated signals to which bacteria and fungi respond. Contributions from those working on the genetics, molecular biology, and physiology of bacteria, fungi, and plants will be required to address these questions. The many nonpathogenic plant-microbe interactions in addition to the Rhizobium-plant interaction remain relatively unexplored. Genetic and molecular approaches are being initiated to investigate the signaling that is likely to underlie interactions such as those between mycorrhizal fungi and plant roots and between epiphytic bacteria and plant leaf surfaces. The importance of these interactions to plant growth and development makes it likely that they will figure more prominently at future symposia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423588 TI - Protein splicing in the maturation of M. tuberculosis recA protein: a mechanism for tolerating a novel class of intervening sequence. AB - The M. tuberculosis recA locus comprises an 85 kd open reading frame but produced 38 kd RecA and 47 kd products in E. coli. No RNA processing was detected; rather, an 85 kd precursor protein was spliced, releasing a 47 kd spacer protein, and joining its terminal fragments to form mature RecA protein. "Spacer" protein was also produced in M. tuberculosis and from a hybrid spacer-LacZ alpha fusion molecule. Mutagenesis at codon wobble positions at one splice junction showed that protein rather than nucleotide sequence determined splicing activity. Other mutants defined additional regions needed for splicing and allowed processing to be followed. Splicing was essential for RecA activity in E. coli. The possibility that splicing is a manifestation of a novel class of genetic element is discussed. PMID- 1423589 TI - PCF4 encodes an RNA polymerase III transcription factor with homology to TFIIB. AB - A dominant mutation in the PCF4 gene of S. cerevisiae was isolated as a suppressor of a tRNA gene A block promoter mutation. In vitro studies indicate that PCF4 is a stoichiometrically-required RNA polymerase III (pol III) transcription initiation factor. We show that the PCF4-1 mutation increases the number of transcriptionally competent preinitiation complexes by affecting a limiting activity in yeast cell extracts that is squelched by excess TFIIIC. The PCF4 gene encodes a TFIIB homolog whose size, biochemical, and genetic properties are consistent with those of the 70 kd subunit of TFIIIB. The TFIIB homology of PCF4 suggests a means for determining the polymerase specificity of a gene. PMID- 1423590 TI - A suppressor of TBP mutations encodes an RNA polymerase III transcription factor with homology to TFIIB. AB - The TDS4 gene of S. cerevisiae was isolated as an allele-specific high copy suppressor of mutations within the basic region of the TATA-binding protein (TBP). The gene is essential for viability and encodes a 596 aa protein. The first 300 aa of the TDS4 protein exhibit significant sequence similarity to the RNA polymerase II transcription factor TFIIB. However, TDS4 is required for RNA polymerase III transcription in vivo and in vitro. Antibodies specific for TDS4 or TBP react with the TFIIIB complex, indicating that both proteins are components of the RNA polymerase III initiation complex. These findings suggest that the RNA polymerase II and III initiation mechanisms are extremely similar, and they explain how the TATA-binding protein can function in both systems. PMID- 1423591 TI - A novel B cell-derived coactivator potentiates the activation of immunoglobulin promoters by octamer-binding transcription factors. AB - A novel B cell-restricted activity, required for high levels of octamer/Oct dependent transcription from an immunoglobulin heavy chain (IgH) promoter, was detected in an in vitro system consisting of HeLa cell-derived extracts complemented with fractionated B cell nuclear proteins. The factor responsible for this activity was designated Oct coactivator from B cells (OCA-B). OCA-B stimulates the transcription from an IgH promoter in conjunction with either Oct 1 or Oct-2 but shows no significant effect on the octamer/Oct-dependent transcription of the ubiquitously expressed histone H2B promoter and the transcription of USF- and Sp1-regulated promoters. Taken together, our results suggest that OCA-B is a tissue-, promoter-, and factor-specific coactivator and that OCA-B may be a major determinant for B cell-specific activation of immunoglobulin promoters. In light of the evidence showing physical and functional interactions between Oct factors and OCA-B, we propose a mechanism of action for OCA-B and discuss the implications of OCA-B for the transcriptional regulation of other tissue-specific promoters. PMID- 1423592 TI - The precursor of NF-kappa B p50 has I kappa B-like functions. AB - The C-terminal half of the p105 precursor of the NF-kappa B p50 subunit contains ankyrin-like repeats similar to those in I kappa B molecules, which are known to retain NF-kappa B complexes in the cytoplasm. We demonstrate that in various cell lines p105 is found associated with either c-rel or p65 in the cytoplasm and serves I kappa B-like functions. p105 retains c-rel or p65 in the cytoplasm in cotransfection experiments in COS cells. It also inhibits DNA binding by c-rel in gel retardation assays. Stable interaction of p105 with c-rel or p65 requires the putative dimerization domain in the conserved rel homology region of p105, as well as a second contact with the I kappa B-related C-terminal part of p105. Pulse-chase experiments indicate that cytoplasmic complexes of p105 with c-rel or p65 give rise to cytoplasmic as well as nuclear p50-c-rel and p50-p65, respectively, probably through processing of p105. Thus, p105, like the I kappa Bs, controls the subcellular localization and hence the transcriptional activity of at least two other members of the rel/NF-kappa B family. PMID- 1423593 TI - The chromatin-associated protein H-NS interacts with curved DNA to influence DNA topology and gene expression. AB - H-NS is an abundant structural component of bacterial chromatin and influences many cellular processes, including recombination, transposition, and transcription. We have studied the mechanism of action of H-NS at the osmotically regulated proU promoter. The interaction of H-NS with a curved DNA element located downstream of the proU promoter is required for normal regulation of expression. Heterologous curved sequences can replace the regulatory role of the proU curve. Hence, the luxAB and lacZ reporter genes, which differ in the presence or absence of a curve, can indicate very different patterns of transcription. H-NS interacts preferentially with these curved DNA elements in vitro. Furthermore, in vivo the interaction of H-NS with curved DNA participates in the control of plasmid linking number. The data suggest that H-NS-dependent changes in DNA topology play a role in the osmoregulation of proU expression. PMID- 1423594 TI - The arrest of replication forks in the rDNA of yeast occurs independently of transcription. AB - Replication forks, moving opposite to the direction of transcription, are arrested at the 3' ends of the 35S transcription units in the rDNA locus of S. cerevisiae. Because of its position and polarity, we tested the hypothesis that this replication fork barrier (RFB) results from the act of transcription. Three results contradict this hypothesis. First, the RFB persists in a strain containing a disruption of the gene for the 135 kd subunit of RNA polymerase I. Second, the RFB causes a polar arrest of replication forks when transplanted to a plasmid. Third, transcription by RNA polymerase II of a plasmid copy of the 35S transcription unit lacking the RFB does not generate a barrier. We propose that replication forks are arrested in a directional manner through the binding of one or more proteins to two closely spaced sites in the RFB. PMID- 1423595 TI - Localization of nanos RNA controls embryonic polarity. AB - Anterior-posterior polarity of the Drosophila embryo is initiated during oogenesis through differential maternal RNA localization. The RNA of the anterior morphogen bicoid is localized to the anterior pole of the embryo, where bicoid protein controls head and thorax development. The RNA of the posterior morphogen nanos is localized to the posterior pole, where nanos protein is required for abdomen formation. Here we show that the nanos 3' untranslated region, like that of the bicoid RNA, is sufficient for RNA localization. We have used the bicoid RNA localization signal to mislocalize nanos, producing embryos with two sources of nanos protein. Such embryos form two abdomens with mirror image symmetry. Embryos with nanos RNA localized only to the anterior have greater nanos gene activity than embryos with nanos RNA localized posteriorly. We propose a role for RNA localization in regulating nanos activity. PMID- 1423596 TI - Cytotoxicity with target DNA breakdown by rat basophilic leukemia cells expressing both cytolysin and granzyme A. AB - The noncytotoxic rat mast cell tumor line RBL was transfected with genes for the cytotoxic lymphocyte granule proteins cytolysin (perforin) and granzyme A, giving transfectants with mRNA and protein expression levels comparable with cloned cytotoxic T lymphocytes. Both RBL-cytolysin and RBL-cytolysin-granzyme A transfectants showed extremely potent killing of red cell targets and lysed 20% 60% of EL4 lymphoma targets at an effector-to-target ratio of 30. RBL transfectants expressing only granzyme A were not cytotoxic. Significant EL4 DNA breakdown accompanying lysis was observed only with RBL that was transfected with both cytolysin and granzyme A. These results support the granule-exocytosis model for lymphocyte cytotoxicity and show that effector granzyme A plays a role in target cell DNA breakdown. PMID- 1423597 TI - Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins. AB - Murine D type cyclins associate with a catalytic subunit (p34PSK-J3) with properties distinct from known cyclin-dependent kinases (cdks). Mouse p34PSK-J3 shows less than 50% amino acid identity to p34cdc2, p33cdk2, and p36cdk3, lacks a PSTAIRE motif, and does not bind to p13suc1. Cyclin D1-p34PSK-J3 complexes accumulate in macrophages during G1 and decline in S phase, whereas complexes involving cyclins D2 and D3 form in proliferating T cells. Although histone H1 kinase activity is not detected in cyclin D or PSK-J3 immunoprecipitates, cyclin D-p34PSK-J3 complexes assembled in vitro stably bind and phosphorylate the retinoblastoma gene product (pRb) and an Rb-like protein (p107) but do not interact with pRb mutants that are functionally inactive. Thus, p34PSK-J3 is a cyclin D-regulated catalytic subunit that acts as an Rb (but not H1) kinase. PMID- 1423598 TI - Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. AB - apoE-deficient mice have been created by homologous recombination in ES cells. On a low fat, low cholesterol chow diet these animals have plasma cholesterol levels of 494 mg/dl compared with 60 mg/dl in control animals, and when challenged with a high fat Western-type diet, these animals have plasma cholesterol levels of 1821 mg/dl compared with 132 mg/dl in controls. This marked hypercholesterolemia is primarily due to elevated levels of very low and intermediate density lipoproteins. At 10 weeks of age, apoE-deficient mice have already developed atherosclerotic lesions in the aorta and coronary and pulmonary arteries. apoE deficient mice are a promising small animal model to help understand the role of apoE in vivo and the genetic and environmental determinants of atherosclerosis. PMID- 1423599 TI - Invasion of the trophoblasts. PMID- 1423600 TI - SH2 and SH3 domains: from structure to function. PMID- 1423601 TI - A question of time: replication origins of eukaryotic chromosomes. PMID- 1423602 TI - Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. AB - The Myf-5 gene, a member of the myogenic basic HLH factor family, has been inactivated in mice after homologous recombination in ES cells. Mice lacking Myf 5 were unable to breathe and died immediately after birth, owing to the absence of the major distal part of the ribs. Other skeletal abnormalities, except for complete ossification of the sternum, were not apparent. Histological examination of skeletal muscle from newborn mice revealed no morphological abnormalities. Northern blot analysis demonstrated normal levels of muscle-specific mRNAs including MyoD, myogenin, and Myf-6. However, the appearance of myotomal cells in early somites was delayed by several days. These results suggest that while Myf-5 plays a crucial role in the formation of lateral sclerotome derivatives, Myf-5 is dispensable for the development of skeletal muscle, perhaps because other members of the myogenic HLH family substitute for Myf-5 activity. PMID- 1423603 TI - Fertility in mice requires X-Y pairing and a Y-chromosomal "spermiogenesis" gene mapping to the long arm. AB - There is accumulating evidence that the mammalian Y chromosome, in addition to its testis-determining function, may have other male limited functions, particularly in spermatogenesis. We have previously shown that the short arm of the mouse Y carries information needed for spermatogonial proliferation. This information, together with the testis-determining gene Sry, is contained within the Y-derived sex reversal factor Sxra. XO males carrying a copy of Sxra attached to the X chromosome are nevertheless sterile owing to an almost complete arrest during the meiotic metaphase stages. Here we show that this meiotic block can be overcome by providing a meiotic pairing partner (with no Y-specific DNA) for the XSxra chromosome. However, this does not restore fertility because the sperm produced all have abnormal heads. It is concluded that the Y-specific region of the mouse Y chromosome long arm includes information essential for the normal development of the sperm head. PMID- 1423604 TI - LDL receptor-related protein internalizes and degrades uPA-PAI-1 complexes and is essential for embryo implantation. AB - The low density lipoprotein receptor-related protein (LRP) is a large multifunctional clearance receptor that has been implicated in the hepatic uptake of chylomicron remnants and in the removal of protease-inhibitor complexes from the circulation and from the extracellular space. Disruption of the LRP gene in mice blocks development of LRP-/- embryos around the implantation stage. The expression pattern of LRP in the postimplantation stage embryo is identical to that of urokinase, a plasminogen activator that confers invasive properties to migrating cells. We demonstrate that LRP mediates uptake and degradation of urokinase-type plasminogen activator-plasminogen activator inhibitor 1 complexes and propose that the inability of the giant cells to remove the inactive protease complexes from their surfaces interferes with implantation of the embryo. PMID- 1423605 TI - Differentiation of an immature T cell line: a model of thymic positive selection. AB - Thymocyte differentiation is dependent upon recognition of major histocompatibility complex (MHC) molecules on thymic stroma, a process called positive selection. Here we describe an immature CD4+8+ T cell line derived from a TCR transgenic mouse that differentiates into CD4+8- cells in response to antigen and nonthymic antigen-presenting cells. When injected intrathymically, these cells differentiate in the absence of antigen. The ability of immature T cells to recognize MHC molecules in the absence of foreign antigen in the thymus can thus be attributed to a unique property of thymic antigen-presenting cells. These studies also demonstrate the phenotypic and functional changes associated with TCR-mediated T cell maturation and establish an in vitro model system of positive selection. PMID- 1423606 TI - Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. AB - Zygotic expression of the Drosophila TGF beta family member decapentaplegic (dpp) is required for the development of the dorsal embryonic structures. By injecting dpp transcripts into young embryos, we find that 2- to 4-fold increases in the concentration of injected RNA elicit progressively more dorsal cell fates: only low levels of dpp permit development of ventral ectoderm, intermediate dpp levels drive dorsal epidermal development, and high dpp levels drive cells to differentiate as the most dorsal pattern element, the amnioserosa. Localized dpp RNA injections into embryos that lack all known maternal and zygotic dorsal ventral polarity indicate that dpp can both define embryonic polarity and organize detailed patterning within the ectoderm. We infer that dpp acts as an extracellular morphogen and that the graded activity of dpp specifies the pattern of ectodermal cell fates in the Drosophila embryo. PMID- 1423607 TI - SHR3: a novel component of the secretory pathway specifically required for localization of amino acid permeases in yeast. AB - Mutations in SHR3 block amino acid uptake into yeast by reducing the levels of multiple amino acid permeases within the plasma membrane. SHR3 is a novel integral membrane protein component of the endoplasmic reticulum (ER). shr3 null mutants specifically accumulate amino acid permeases in the ER; other plasma membrane proteins, secretory proteins, and vacuolar proteins are processed and targeted correctly. Our findings suggest that SHR3 interacts with a structural domain shared by amino acid permeases, an interaction required for permease specific processing and transport from the ER. Even in the presence of excess amino acids, shr3 mutants exhibit starvation responses. shr3 mutants constitutively express elevated levels of GCN4, and mutant shr3/shr3 diploids undergo dimorphic transitions that result in filamentous growth at enhanced frequencies. PMID- 1423608 TI - The reovirus cell attachment protein possesses two independently active trimerization domains: basis of dominant negative effects. AB - The reovirus cell attachment protein, sigma 1, is a homotrimer with an N-terminal fibrous tail and a C-terminal globular head. By cotranslating full-length and various truncated sigma 1 proteins in vitro, we show that the N- and C-terminal halves of sigma 1 possess independent trimerization and folding domains. Trimerization of sigma 1 is initiated at the N-terminus by the formation of a "loose," protease-sensitive, three-stranded, alpha-helical coiled coil. This serves to bring the three unfolded C-termini into close proximity to one another, facilitating their subsequent trimerization and cooperative folding. Concomitant with, but independent of, this latter process, the N-terminal fiber further matures into a more stable and protease-resistant structure. The coordinated folding of sigma 1 trimers exemplifies the dominant negative effects of mutant subunits in oligomeric complexes. PMID- 1423609 TI - A mammalian homolog of SEC61p and SECYp is associated with ribosomes and nascent polypeptides during translocation. AB - SEC61p is essential for protein translocation across the endoplasmic reticulum membrane of S. cerevisiae. We have found a mammalian homolog that shows more than 50% sequence identity with the yeast protein. Moreover, several regions of SEC61p have significant similarities with corresponding ones of SecYp of bacteria, indicating a strong evolutionary conservation of the mechanism of protein translocation. Mammalian Sec61p, like the yeast protein, is located in the immediate vicinity of nascent polypeptides during their membrane passage. It is tightly associated with membrane-bound ribosomes, suggesting that the nascent chain passes directly from the ribosome into a protein-conducting channel. These results define Sec61p as a ubiquitous key component of the protein translocation apparatus. PMID- 1423610 TI - The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. AB - The Xist gene maps to the X inactivation center region in both mouse and human, and previous analysis of the 3' end of the gene has demonstrated inactive X specific expression, suggesting a possible role in X inactivation. We have now analyzed the entire mouse Xist gene. The mature inactive X-specific transcript is 15 kb in length and contains no conserved ORF. The Xist sequence contains a number of regions comprised of tandem repeats. Comparison with the human XIST gene demonstrates significant conservation of sequence and gene structure. Xist RNA is not associated with the translational machinery of the cell and is located almost exclusively in the nucleus. Together with conservation of inactive X specific expression, these findings support a role for Xist in X inactivation, possibly as a functional RNA or as a chromatin organizer region. PMID- 1423612 TI - Defects in a cell cycle checkpoint may be responsible for the genomic instability of cancer cells. PMID- 1423611 TI - The human XIST gene: analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. AB - X chromosome inactivation in mammalian females results in the cis-limited transcriptional inactivity of most of the genes on one X chromosome. The XIST gene is unique among X-linked genes in being expressed exclusively from the inactive X chromosome. Human XIST cDNAs containing at least eight exons and totaling 17 kb have been isolated and sequenced within the region on the X chromosome known to contain the X inactivation center. The XIST gene includes several tandem repeats, the most 5' of which are evolutionarily conserved. The gene does not contain any significant conserved ORFs and thus does not appear to encode a protein, suggesting that XIST may function as a structural RNA within the nucleus. Consistent with this, fluorescence in situ hybridization experiments demonstrate localization of XIST RNA within the nucleus to a position indistinguishable from the X inactivation-associated Barr body. PMID- 1423613 TI - Force and counterforce in the mitotic spindle. PMID- 1423614 TI - What's new with calcium? PMID- 1423615 TI - Pleiotropic effects of a null mutation in the c-fos proto-oncogene. AB - The c-fos proto-oncogene has been implicated as a central regulatory component of the nuclear response to mitogens and other extracellular stimuli. Embryonic stem cells targeted at the c-fos locus have been used to generate chimeric mice that have transmitted the mutated allele through the germline. Homozygous mutants show reduced placental and fetal weights and significant loss of viability at birth. Approximately 40% of the homozygous mutants survive and grow at normal rates until severe osteopetrosis, characterized by foreshortening of the long bones, ossification of the marrow space, and absence of tooth eruption, begins to develop at approximately 11 days. Among other abnormalities, these mice show delayed or absent gametogenesis, lymphopenia, and altered behavior. Despite these defects, many live as long as their wild-type or heterozygous littermates (currently 7 months). These data indicate that c-fos is not required for the growth of most cell types but is involved in the development and function of several distinct tissues. PMID- 1423616 TI - A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. AB - Cell cycle checkpoints can enhance cell survival and limit mutagenic events following DNA damage. Primary murine fibroblasts became deficient in a G1 checkpoint activated by ionizing radiation (IR) when both wild-type p53 alleles were disrupted. In addition, cells from patients with the radiosensitive, cancer prone disease ataxia-telangiectasia (AT) lacked the IR-induced increase in p53 protein levels seen in normal cells. Finally, IR induction of the human GADD45 gene, an induction that is also defective in AT cells, was dependent on wild-type p53 function. Wild-type but not mutant p53 bound strongly to a conserved element in the GADD45 gene, and a p53-containing nuclear factor, which bound this element, was detected in extracts from irradiated cells. Thus, we identified three participants (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development. PMID- 1423617 TI - The ts41 mutation in Chinese hamster cells leads to successive S phases in the absence of intervening G2, M, and G1. AB - The ts41 mutation of Chinese hamster cells was first isolated and characterized by Hirschberg and Marcus (1982) who showed that at nonpermissive temperature, cells accumulate up to 16C equivalents of DNA. Here we show that the mutation is recessive and at nonpermissive temperature, cells replicate their genome normally, but instead of going on into G2, M, and G1, they pass directly into a second S phase. Entry into a second S phase does not require serum nor is it inhibited by G2 checkpoints or mitotic inhibitors. Temperature-shift experiments suggest that the ts41 gene product participates in two functions in the cell cycle: entry into mitosis and inhibition of entry into S phase. The ts41 mutation seems to define a class of cell cycle mutant that couples the sequential events of DNA replication and mitosis. PMID- 1423618 TI - cactus, a gene involved in dorsoventral pattern formation of Drosophila, is related to the I kappa B gene family of vertebrates. AB - Among the maternally active genes of Drosophila, cactus is the only one whose loss of function mutations specifically produce ventralized embryos. Its product inhibits nuclear translocation of the dorsal morphogen in the dorsal region of the embryo. Here we report the cloning of cactus and the sequencing of its maternal transcript. The identity of our clones was verified by induction of phenocopies with antisense RNA and rescue of the mutant phenotype with sense RNA. cactus is predicted to encode an acidic, cytoplasmic protein with seven ankyrin repeats. The sequence has similarity to the I kappa B proteins that inhibit the vertebrate transcription factor NF-kappa B. In analogy to results obtained with I kappa B and NF-kappa B, bacterially expressed cactus protein can inhibit DNA binding of dorsal protein in vitro. PMID- 1423619 TI - Characterization of the Drosophila cactus locus and analysis of interactions between cactus and dorsal proteins. AB - An oligonucleotide based on the cdc 10/SWI6 repeats of the Drosophila Notch protein was used to isolate other Drosophila genes with these repeats. One of these genes is the cactus locus, 1 of 11 genes required maternally for the establishment in embryos of a gradient of nuclear localization of dorsal protein, a rel-like transcription factor. Previous work showed that in cactus mutants more dorsal protein enters the nucleus in dorsal regions, resulting in a ventralized phenotype. It is now shown that the cactus locus produces two proteins that differ at their carboxy termini; both contain six cdc 10/SWI6 repeats that are sufficient for binding to dorsal and for inhibiting the ability of dorsal to bind DNA. The site on dorsal to which cactus binds was localized to the rel homology domain, where it overlaps with, or is adjacent to, the nuclear localization signal. In vivo the bulk of the cactus protein associated with dorsal is phosphorylated. This, or the association with dorsal, appears to stabilize the maternal cactus protein. PMID- 1423620 TI - Analysis of a spatially regulated phosphotyrosine phosphatase identifies tyrosine phosphorylation as a key regulatory pathway in Dictyostelium. AB - We have cloned a Dictyostelium phosphotyrosine phosphatase (PTP1) with a catalytic domain showing approximately 38%-50% amino acid identity to those of other PTPs. PTP1 contains an approximately 99 amino acid insert and bacterially produced PTP1 possesses PTP activity. PTP1 is expressed at a very low level in vegetative cells, induced by 4 hr, and maximally expressed at the tight aggregate stage. PTP1-lacZ studies indicate that PTP1 is spatially localized to prestalk and anterior-like cell types. PTP1 gene disruptants show accelerated development, whereas strains overexpressing PTP1 to a high level fail to aggregate. Strains overexpressing moderate levels exhibit severe morphological defects following aggregation, including multiply tipped aggregates and morphologically aberrant fruiting bodies. Western blot analysis using anti-phosphotyrosine antibodies shows specific changes in the mutant strains when compared with wild-type cells. The results indicate that reversible protein-tyrosine phosphorylation and PTP1 play important regulatory roles during Dictyostelium development. PMID- 1423621 TI - ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. AB - Protein-tyrosine kinases (PTKs) play an integral role in T cell activation. Stimulation of the T cell antigen receptor (TCR) results in tyrosine phosphorylation of a number of cellular substrates. One of these is the TCR zeta chain, which can mediate the transduction of extracellular stimuli into cellular effector functions. We have recently identified a 70 kd tyrosine phosphoprotein (ZAP-70) that associates with zeta and undergoes tyrosine phosphorylation following TCR stimulation. Here we report the isolation of a cDNA clone encoding ZAP-70. ZAP-70 represents a novel PTK and is expressed in T and natural killer cells. Moreover, tyrosine phosphorylation and association of ZAP-70 with zeta require the presence of src family PTKs and provide a potential mechanism by which the src family PTKs and ZAP-70 may interact to mediate TCR signal transduction. PMID- 1423622 TI - The three-dimensional structure of the tenth type III module of fibronectin: an insight into RGD-mediated interactions. AB - The solution structure of the tenth type III module of fibronectin has been determined using nuclear magnetic resonance techniques. The molecule has a fold similar to that of immunoglobulin domains, with seven beta strands forming two antiparallel beta sheets, which pack against each other. Both beta sheets contribute conserved hydrophobic residues to a compact core. The topology is more similar to that of domain 2 of CD4, PapD, and the extracellular domain of the human growth hormone receptor than to that of immunoglobulin C domains. The module contains an Arg-Gly-Asp sequence known to be involved in cell adhesion. This tripeptide is solvent exposed and lies on a conformationally mobile loop between strands F and G, consistent with its cell adhesion function. PMID- 1423623 TI - RNA and DNA binding zinc fingers in Xenopus TFIIIA. AB - The nine tandem zinc finger repeats in the 5S gene-specific transcription factor IIIA (TFIIIA) from Xenopus mediate specific binding to 5S DNA as well as to 5S ribosomal RNA. A comparative functional analysis of a systematic set of TFIIIA zinc finger combinations reveals that most, if not all, participate in both DNA and RNA binding. Minimal sets of fingers sufficient for DNA and RNA recognition are different. In RNA binding, most finger elements are found to be functionally equivalent. However, the nonessential finger 6 exhibits RNA binding characteristics distinct from the other eight modules. The secondary/tertiary structure of the central domain in 5S RNA, not its primary sequence, is found to carry the essential structural information for TFIIIA binding in Xenopus oocytes. Taken together, our findings suggest that RNA and DNA binding are overlapping, though separable functions of the nine zinc finger elements in TFIIIA, occurring via fundamentally different molecular mechanisms. PMID- 1423624 TI - Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. AB - We have identified a human homolog of the Drosophila trithorax protein that is structurally altered by 11q23 translocations in acute leukemias. Human trithorax (HRX) is a predicted 431 kd protein containing two potential DNA-binding motifs consisting of zinc fingers conserved with the fly protein and nonconserved amino terminal "AT hook" motifs related to the DNA-binding motifs in HMG proteins. 11q23 translocations disrupt the HRX gene between these two motifs, and in a t(11;19)-carrying cell line fusion transcripts are expressed from both derivative chromosomes. The more abundant derivative 11 transcript codes for a chimeric protein containing the AT hook motifs fused to a previously undescribed protein (ENL) from chromosome 19. These data suggest a novel role for a trithorax homologous protein in multilineage human leukemias that may be mediated by DNA binding within the minor groove at AT-rich sites, implicated to play an important role in bacterial IHF-, yeast datin-, and mammalian HMG-mediated gene activation. PMID- 1423625 TI - The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. AB - The ALL-1 gene located at human chromosome 11 band q23 is rearranged in acute leukemias with interstitial deletions or reciprocal translocations between this region and chromosomes 1, 4, 6, 9, 10, or 19. The gene spans approximately 100 kb of DNA and contains at least 21 exons. It encodes a protein of more than 3910 amino acids containing three regions with homology to sequences within the Drosophila trithorax gene, including cysteine-rich regions that can be folded into six zinc finger-like domains. The breakpoint cluster region within ALL-1 spans 8 kb and encompasses several small exons, most of which begin in the same phase of the open reading frame. The t(4;11) chromosome translocation results in two reciprocal fusion products coding for chimeric proteins derived from ALL-1 and from a gene on chromosome 4. This suggests that each 11q23 abnormality gives rise to a specific oncogenic fusion protein. PMID- 1423626 TI - Competence modifiers synergize with growth factors during mesoderm induction and patterning in Xenopus. PMID- 1423627 TI - The MARCKS brothers: a family of protein kinase C substrates. PMID- 1423628 TI - Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. AB - The potent mesoderm-inducing factors activin and FGF are present as maternally synthesized proteins in embryos of X. laevis. We show that activin can act on explanted blastomeres to induce at least five different cell states ranging from posterolateral mesoderm to dorsoanterior organizer mesoderm. Each state is induced in a narrow dose range bounded by sharp thresholds. By contrast, FGF induces only posterolateral markers and does so over relatively broad dose ranges. FGF can modulate the actions of activin, potentiating them and broadening the threshold-bounded dose windows. Our results indicate that orthogonal gradients of activin and FGF would be sufficient to specify the main elements of the body plan. PMID- 1423629 TI - Basolateral sorting of LDL receptor in MDCK cells: the cytoplasmic domain contains two tyrosine-dependent targeting determinants. AB - In MDCK cells, transport of membrane proteins to the basolateral plasma membrane has been shown to require a distinct cytoplasmic domain determinant. Although the determinant is often related to signals used for localization in clathrin-coated pits, inactivation of the coated pit domain in the human LDL receptor did not affect basolateral targeting. By expressing mutant and chimeric LDL receptors, we have now identified two independently acting signals that are individually sufficient for basolateral targeting. The two determinants mediate basolateral sorting with different efficiencies, but both contain tyrosine residues critical for activity. The first determinant was colinear with, but distinct from, the coated pit domain of the receptor. The second was found in the C-terminal region of the cytoplasmic domain of the receptor and, although tyrosine-dependent, did not mediate endocytosis. The results suggest that membrane proteins can have functionally redundant signals for basolateral transport and that a tyrosine containing motif may be a common feature of multiple intracellular sorting events. PMID- 1423630 TI - COP1, an Arabidopsis regulatory gene, encodes a protein with both a zinc-binding motif and a G beta homologous domain. AB - Plant seedling development is capable of following 1 of 2 distinct morphogenic pathways: skotomorphogenesis in darkness and photomorphogenesis in light. Dark grown Arabidopsis seedlings with recessive mutations at the constitutively photomorphogenic (COP1) locus indicate that the wild-type COP1 protein represses photomorphogenesis in darkness and that light reverses this repressive activity. Using a T-DNA-tagged mutant, we have cloned the COP1 locus. The amino-terminal half of the encoded protein contains a conserved zinc-binding motif, whereas the carboxyl-terminal half contains a domain homologous to the WD-40 repeat motif of G beta proteins. The presence of both a putative DNA-binding motif and a G protein-related domain in a single polypeptide suggests that COP1 may be the first of a new class of regulatory molecules. This novel structure could endow COP1 with the capacity to function as a negative transcriptional regulator capable of direct interaction with components of the G protein signaling pathway. PMID- 1423631 TI - A novel base-pairing interaction between U2 and U6 snRNAs suggests a mechanism for the catalytic activation of the spliceosome. AB - Prior to the chemical steps of mRNA splicing, the extensive base-pairing interaction between the U4 and U6 spliceosomal snRNAs is disrupted. Here, we use a mutational analysis in yeast to demonstrate a conserved base-pairing interaction between the U6 and U2 snRNAs that is mutually exclusive with the U4 U6 interaction. In this novel pairing, conserved sequences in U6 interact with a sequence in U2 that is immediately upstream of the branch point recognition region. Remarkably, the residues in U6 that can be consequently juxtaposed with the intron substrate include those that have been proposed previously to be catalytic. Both the first and second steps of splicing are inhibited when this base-paired structure is mutated. These observations, together with the high conservation of the U2-U6 structure, lead us to propose that it might be a component of the spliceosomal active site. PMID- 1423632 TI - Mutational analysis of the yeast U2 snRNA suggests a structural similarity to the catalytic core of group I introns. AB - We have used an in vitro reconstitution system to determine the effects of a large number of mutations in the highly conserved 5' terminal domain of the yeast U2 snRNA on pre-mRNA splicing. Whereas many mutations have little or no functional consequence, base substitutions in two regions were found to have drastic effects on pre-mRNA splicing. A previously unrecognized function for the U2 snRNA in the second step of splicing was found by alteration of the absolutely conserved sequence AGA upstream of the branch point recognition sequence. The effects of these mutations suggest the formation of a structure involving the U2 snRNA similar to the guanosine-binding site found in the catalytic core of group I introns. PMID- 1423633 TI - Nucleosome disruption at the yeast PHO5 promoter upon PHO5 induction occurs in the absence of DNA replication. AB - Activation of the PHO5 gene in S. cerevisiae by phosphate starvation was previously shown to be accompanied by the disappearance of four positioned nucleosomes from the promoter. To investigate the mechanism, we replaced the PHO80 gene, a negative regulator of PHO5, by a temperature-sensitive allele. As a consequence, PHO5 can be activated in the presence of phosphate by a temperature shift from 24 degrees C to 37 degrees C. Under these conditions, the promoter undergoes the same chromatin transition as in phosphate-starved cells. Disruption of the nucleosomes by the temperature shift also occurs when DNA replication is prevented. Nucleosomes re-form when the temperature is shifted from 37 degrees C back to 24 degrees C in nondividing cells. Glucose is required for the disruption of the nucleosomes during the temperature upshift, not for their re-formation during the temperature downshift. These experiments prove that DNA replication is not required for the transition between the nucleosomal and the non-nucleosomal state at the PHO5 promoter. PMID- 1423634 TI - A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. AB - Tissue-specific patterns of methylated deoxycytidine residues in the mammalian genome are preserved by postreplicative methylation of newly synthesized DNA. DNA methyltransferase (MTase) is here shown to associate with replication foci during S phase but to display a diffuse nucleoplasmic distribution in non-S phase cells. Analysis of DNA MTase-beta-galactosidase fusion proteins has shown that association with replication foci is mediated by a novel targeting sequence located near the N-terminus of DNA MTase. This sequence has the properties expected of a targeting sequence in that it is not required for enzymatic activity, prevents proper targeting when deleted, and, when fused to beta galactosidase, causes the fusion protein to associate with replication foci in a cell cycle-dependent manner. PMID- 1423635 TI - Regulation of the specific DNA binding function of p53. AB - The DNA binding activity of p53 is required for its tumor suppressor function; we show here that this activity is cryptic but can be activated by cellular factors acting on a C-terminal regulatory domain of p53. A gel mobility shift assay demonstrated that recombinant wild-type human p53 binds DNA sequence specifically only weakly, but a monoclonal antibody binding near the C terminus activated the cryptic DNA binding activity stoichiometrically. p53 DNA binding could be activated by a C-terminal deletion of p53, mild proteolysis of full-length p53, E. coli dnaK (which disrupts protein-protein complexes), or casein kinase II (and coincident phosphorylation of a C-terminal site on p53). Activation of p53 DNA binding may be critical in regulation of its ability to arrest cell growth and thus its tumor suppressor function. PMID- 1423636 TI - Casein kinase II is a negative regulator of c-Jun DNA binding and AP-1 activity. PMID- 1423637 TI - The impairment of natural killer function in the healthy aged is due to a postbinding deficient mechanism. AB - In order to study the fine mechanisms that underlie the impairment of non-MHC restricted cytolytic activity which occurs during human aging, we examined by multiparametric flow cytometry the binding and lytic activities of human natural killer cells. The flow analysis revealed a striking increase of the CD16+8- subset, together with a significant decrease of CD8bright cells and total T cells (CD3+). Aging had no influence on the CD8dim subset. The total lytic activity expressed by PBL as well as their binding efficiency to K562 targets were moderately but not significantly increased in the elderly. In contrast, the cytotoxicity of the single target-bound natural killer cell (i.e., lytic efficiency) was deeply impaired in aged subjects, suggesting that the NK functional impairment observed in aging is located at postbinding level. PMID- 1423638 TI - Synergistic enhancement of T cell responses and interleukin-1 receptor expression by interleukin-1 and heparin or dextran sulfate. AB - Heparin markedly enhances generation of cytotoxic T lymphocytes against allogeneic cells and histocompatible tumors. In this study, we demonstrated a marked synergism between heparin and low concentrations of recombinant IL-1-alpha and IL-1-beta in enhancement of cytotoxic T cell responses in mice. Low molecular weight (8000 Da) dextran sulfate also enhanced the T cell responses and synergized with IL-1, whereas, de-N-sulfated heparin was devoid of both of these activities. The synergistic effect was selective for IL-1, because there was no synergism between heparin or dextran sulfate and other cytokines (tumor necrosis factor-alpha, IL-4, and, as shown previously, IL-2). Heparin did not increase the production of IL-1 (and IL-2, as shown before). Heparin did not bind to IL-1, despite significant amino acid homology between IL-1 and heparin-binding endothelial cell growth factors. Heparin enhanced the growth-promoting effect of IL-1 on the IL-1-dependent helper T cell clone, D10.G4.1, and enhanced IL-1 receptor expression on these cells. These data indicate that heparin acts directly on the T cells and enhances their responsiveness to IL-1 by up regulating IL-1 receptor expression. PMID- 1423639 TI - Abnormal activation and loss of suppressor T cells in the spontaneously hypertensive rat. AB - Suppressor T cell function in the spontaneously hypertensive rat (SHR) and normotensive Wistar Kyoto (WKY) rats was analyzed using syngeneic mixed lymphocyte reaction (SMLR) and concanavalin A (Con A) activation. A depressed SMLR was found in adult SHR but not in adult WKY. IL-2 synthesized by SHR was 40 fold lower than that of WKY, and the suppressor T cells generated in the SMLR were incapable of suppressing IgG synthesis. Precursors of cells that can be activated by Con A to become functional suppressor cells are reduced in adult SHR. Supernatant fluids derived from Con A-activated spleen cells from adult SHR failed to significantly inhibit IgG synthesis by cultures of syngeneic spleen cells compared to supernatant fluids from young SHR or WKY Con A-activated spleen cells. However, spleen cells from both adult SHR and WKY proliferated strongly and released equivalent amounts of IL-2 in response to Con A. Addition of exogenous IL-2 to the SMLR cultures in vitro restored the ability of SHR T cells to respond in the SMLR, with generation of cells capable of suppressing IgG synthesis. Administration of SHR with IL-2 in vivo also restored the suppressor T cell function in the SMLR. These results suggest a defective suppressor T cell activation and loss of suppressor T cell activity as the SHR age. PMID- 1423640 TI - Stress stimuli-induced lymphocyte activation. AB - Oxidants, heavy metals, and heat shock, collectively known as stress stimuli, induce the synthesis of a variety of proteins, termed stress proteins, and enhance glucose uptake. In this study, we have demonstrated that stress stimuli enhance protein tyrosine phosphorylation (PTyr-P), modulate protein tyrosine phosphatase (PTPase) activity, activate the src family protein tyrosine kinase (PTK), p56lck, and enhance glucose uptake in human peripheral blood mononuclear cells. The heavy metal Hg2+ and heat shock stimulated PTPase activity at an optimal dose, whereas the oxidant phenylarsine oxide (PAO) was only marginally stimulatory. Treatment of lymphocytes with stress stimuli at a dose which activated PTPase did not produce discernable PTyr-P using Western blotting techniques. PTyr-P was only seen at doses of stress stimuli which were associated with an inhibition of PTPase activity. We could demonstrate a correlation between the dose of stress stimuli effective in increasing PTPase activity and p56lck activation using heat shock and Hg2+ as stress stimuli. On the other hand, much lower concentrations of PAO were effective in activating PTPase than those effective in eliciting p56lck activation. We could not demonstrate a correlation between an effective dose inducing PTyr-P and glucose uptake. Our data do not permit us to draw a simple correlation between enhancement of PTPase activity, activation of p56lck, induction of PTyr-P, and induction of the biological response. It is possible that both stimulation and inhibition of PTPase could regulate PTyr-P by either activating the src family PTKs or preventing dephosphorylation of target proteins which are involved in the biological response. Our data may also provide the biochemical basis for the previously reported mitogenic effects of Hg2+ on lymphocytes. PMID- 1423641 TI - IL-1, IL-6, and PDGF mRNA expression in alveolar cells following stimulation with a tobacco-derived antigen. AB - To test the hypothesis that inflammatory cytokine production might be an early event in the development of the disease associated with smoking, we used alveolar cells from healthy nonsmokers stimulated with TGP as a model system. TGP, a phenol-rich glycoprotein which is present in tobacco leaves and cigarette smoke condensate, activates the immune system. It stimulates polyclonal B cell differentiation, induces primarily an IgE response, and activates human leukocytes to produce IL-1. Using in situ nucleic acid hybridization we show that the steady-state levels of IL-1 alpha, IL-1 beta, IL-6, platelet-derived growth factor (PDGF)-A, and PDGF-B mRNAs are consistently elevated in the alveolar cells of all donors following TGP stimulation. The kinetics of mRNA expression suggest that IL-1 alpha and IL-1 beta mRNAs are independently regulated in alveolar cells, while the regulation of PDGF-A and PDGF-B mRNA seems to be similar. The activated cells also synthesize elevated levels of IL-1 and IL-6. These findings lend support to the suggestion that some clinical consequences of smoking might be initiated and enhanced by the production of inflammatory cytokines. Moreover, IL-6 could also activate a polyclonal B cell response, which could lead to the synthesis of autoantibodies and thus cause immune-mediated tissue injury. PMID- 1423642 TI - The CD45RO (p180, UCHL1) marker: complexity of expression in peripheral blood. AB - Analysis of peripheral blood lymphocytes by two- and three-colour high sensitivity staining with UCHL1 (CD45RO) and other markers shows that the expression of CD45RO on lymphocyte subsets is more complex than is generally supposed. In addition to the populations which express CD45RO and RA in a mutually exclusive manner, up to 30% of cells in adult blood express both markers, at low levels. This "intermediate" population includes CD4-positive cells, and a proportion of these cells express the p55 chain of the IL-2 receptor (CD25), suggesting that they are activated. In cord blood there are few RO-bright cells, but CD45RO is expressed at low intensity on a proportion of cells. Among the CD45RO-bright cells in adult blood at least two subsets can be detected by using MHC Class II and the homing receptor L-selectin as additional markers. This complexity suggests that memory cells are a subset of CD45RO-expressing cells, but that this marker is also found on cells that are activated but not irreversibly "switched" to memory cells. PMID- 1423643 TI - Glutathione influences the proliferation as well as the extent of mitochondrial activation in rat splenocytes. AB - The time-dependent changes of mitochondrial membrane potential and mass have been investigated on rat splenic lymphocytes stimulated with Con A in the presence and absence of reduced glutathione (GSH). Rhodamine-123 (Rh-123) and nonyl acridine orange (NAO) were used as specific dyes to monitor the membrane potential and mass of mitochondria, respectively. The percentage of cells showing blast transformation and the level of Rh-123 or NAO uptake were analyzed by flow cytometry. Present results demonstrate that a large number of cells showed activated mitochondria already at 24 hr after Con A stimulation and the activation of these organelles was not related to blast transformation. The addition of GSH into the culture medium increased the number of cells responding to mitogenic stimulation. In parallel it augmented the percentage of lymphocytes with activated mitochondria and also prevented their depolarization. PMID- 1423644 TI - Tight conjugate formation is not always required for natural killer cell-mediated lysis. AB - We have utilized several clonal cell lines, derived from the murine lymphoma ASL1w, to investigate the early events in NK-mediated lysis. The studies described here examine the relationship between NK recognition, NK cell:tumor cell conjugate formation, and NK-mediated lysis. The AW4F and AW4D tumor lines were susceptible to NK-mediated lysis and efficiently inhibited NK recognition in competitive inhibition assays, whereas the AW5J tumor, which is relatively resistant to NK-mediated lysis, did not. In contrast, the AW5E tumor was NK resistant but inhibited NK recognition almost as well as the NK-sensitive tumors, suggesting that it was deficient in a postbinding event required for NK-mediated lysis. These findings demonstrate a correlation, with one exception, between the susceptibility of the ASL1w-derived tumor lines to NK-mediated lysis and their ability to inhibit NK recognition. In contrast, there was no apparent correlation between tight conjugate formation, as assessed in three independent target binding assays, and the susceptibility of these tumors to NK-mediated lysis, showing that tight conjugate formation is not required for either efficient NK recognition or lysis. PMID- 1423645 TI - Introduction of the H-2Dk gene into a class I-negative tumor cell line confers interferon-gamma inducibility upon the silent endogenous H-2Kk gene. AB - Kgv cells do not constitutively express class I mRNA or protein. Interferon (IFN) gamma, but not IFN-alpha/beta, induces H-2Dk expression. IFN does not induce H 2Kk expression. We examined constitutive and IFN-inducible class I expression on Kgv cells stably transfected with genomic clones of H-2Kk or H-2Dk and on somatic cell hybrid lines constructed between Kgv cells and constitutively class I positive cells of a distinguishable H-2 haplotype. Our results suggest that both the lack of constitutive class I expression and the inability of IFN-alpha/beta to induce class I expression on Kgv cells are primarily due to cis-regulatory mechanisms. However, stable introduction of the H-2Dk gene into Kgv cells conferred IFN-gamma inducibility upon the silent endogenous H-2Kk gene. Therefore, the failure of IFN-gamma to induce H-2Kk expression on Kgv cells is due, at least in part, to a trans-regulatory mechanism. PMID- 1423646 TI - Reduced binding activity of transcription factor NF-kappa B accounts for MHC class I repression in adenovirus type 12 E 1-transformed cells. AB - The early region 1 (E1) of human adenovirus (Ad) type 12 represses the expression of major histocompatibility (MHC) Class I genes in transformed primary rodent cells. In this paper we show that both NF-kappa B and KBF1 (p50 dimer) binding activity to the H2TF1 element in the Class I promoter is reduced in Ad12-13S-E1A transformed cells compared to Ad5E1- or Ad12-12S-E1A-transformed cells. Consistently, in Ad12E1A-13S-transformed cells the H2TF1 element does not contribute to transcriptional activity in transient expression assays, whereas it does contribute in Ad12E1A-12S-transformed cells. Therefore, the most likely explanation is that reduced binding of NF-kappa B and KBF1 to the H2TF1 element accounts for the down-regulation of MHC Class I expression in Ad12E1- and Ad12E1A 13S-transformed cells. PMID- 1423647 TI - Generation of cytotoxicity with various MHC class I restrictions against autologous LCL by stimulating the lymphocytes with autologous and/or allogeneic LCLs sharing HLA alleles with the responder. AB - We exposed human blood lymphocytes to autologous and to allogeneic lymphoblastoid lines (LCLs), each alone or in combination, and analyzed the MHC Class I restriction pattern of the generated auto-LCL reactive cytotoxicity. In the cultures of two EBV-seropositive, HLA A11-positive individuals the majority of cytotoxic lymphocytes generated after repeated stimulation with autologous LCL were restricted by this molecule. One of the cultures was subjected to various stimulation strategies. A relatively low proportion of HLA A2- and HLA B7 restricted cytotoxic T cells could be detected in the autostimulated cultures. Such cells were enriched at the expense of A11-restricted ones by stimulating with allogeneic LCLs which lacked HLA A11 but expressed A2 or B7. Interestingly, stimulation of the lymphocytes with only allogeneic LCL also generated autoreactive CTLs. Thus, by including or using exclusively allogeneic LCL stimulators, the CTL fractions represented by few cells could be enriched. PMID- 1423648 TI - Relative resistance of intermediate TCR cells to anti-CD3 mAb in mice in vivo and their partial functional characterization. AB - In addition to T cells differentiated in the thymus, T cells, possibly of extrathymic origin, were recently demonstrated in the liver of mice. These T cells are characterized by the expression of intermediate TCR and contain double negative CD4-8- cells. A further characterization of intermediate TCR cells was carried out. When mice were injected ip with anti-CD3 mAb, bright TCR cells (i.e., regular T cells) and intermediate TCR cells were reduced on Day 3, depending on the amount of mAb. Because of the resistance of intermediate TCR cells to treatment, injection of an appropriate dose of antibody (i.e., 100 micrograms/mouse) eliminated most bright TCR cells, but not intermediate TCR cells. This dose revealed that a significant proportion of intermediate TCR cells also reside in the periphery. Hepatic and splenic mononuclear cells (MNC), in which intermediate TCR cells became abundant after treatment, showed a unique response to T cell mitogens and IL-2. Thus, the intermediate TCR cell-enriched population could not respond to a T cell mitogen, Con A, but responded well to a super antigen, staphylococcal enterotoxin B, and IL-2. MNC obtained from athymic nude mice, which comprise only intermediate TCR cells, responded in the same manner. These findings revealed that intermediate TCR cells are present not only in the liver but also in the periphery, and that they have a unique function distinct from regular T cells. PMID- 1423649 TI - Microbiological and biotechnological aspects of metabolism of carbamates and organophosphates. AB - Several carbamate and organophosphate compounds are used to control a wide variety of insect pests, weeds, and disease-transmitting vectors. These chemicals were introduced to replace the recalcitrant and hazardous chlorinated pesticides. Although newly introduced pesticides were considered to be biodegradable, some of them are highly toxic and their residues are found in certain environments. In addition, degradation of some of the carbamates generates metabolites that are also toxic. In general, hydrolysis of the carbamate and organophosphates yields less toxic metabolites compared with the metabolites produced from oxidation. Although microorganisms capable of degrading many of these pesticides have been isolated, knowledge about the biochemical pathways and respective genes involved in the degradation is sparse. Recently, a great deal of interest in the mechanisms of biodegradation of carbamate and organophosphate compounds has been shown because (1) an efficient mineralization of the pesticides used for insect control could eliminate the problems of environmental pollution, (2) a balance between degradation and efficacy of pesticides could result in safer application and effective insect control, and (3) knowledge about the mechanisms of biodegradation could help to deal with situations leading to the generation of toxic metabolites and bioremediation of polluted environments. In addition, advances in genetic engineering and biotechnology offer great potential to exploit the degradative properties of microorganisms in order to develop bioremediation strategies and novel applications such as development of economic plants tolerant to herbicides. In this review, recent advances in the biochemical and genetic aspects of microbial degradation of carbamate and organophosphates are discussed and areas in need of further investigation identified. PMID- 1423650 TI - Protein engineering of antibodies. AB - This article reviews the technical advances in antibody engineering and the clinical applications of these molecules. Recombinant DNA technology facilitates the construction and expression of engineered antibodies. These novel molecules are designed to meet specific applications. Although genomic and cDNA cloning have been used widely in the past to isolate the relevant antibody V domains, at present, the PCR-based cloning is the preferred system. Bacterial and mammalian expression systems are used commonly for the production of antibodies, antibody fragments, and antibody fusion proteins. A range of chimeric antibodies with murine V domains joined to C regions from human and other species have been produced and found to exhibit the expected binding characteristics and effector functions. Humanized antibodies have been developed to minimize the HAMA response, and bifunctional immunoglobulins are being used in tumor therapy and diagnosis. Single chain antibodies and fusion proteins with antibody specificities jointed to nonimmunoglobulin sequences provide a source of antibody like molecules with novel properties. The potential applications of minimal recognition units and antigenized antibodies are described. Combinatorial libraries produced in bacteriophage present an alternative to hybridomas for the production of antibodies with the desired antigen binding specificities. Future developments in this field are discussed also. PMID- 1423651 TI - The modulation of collagen synthesis in cultured arterial smooth muscle cells by platelet-derived growth factor. AB - Changes on collagen synthetic activity of cultured arterial smooth muscle cells of rabbits induced with purified platelet-derived growth factor (PDGF) were examined. PDGF treatment (final concentration was 5 units/ml) decreased the total collagen synthesis per cell, while the rate of collagen synthesis against total protein synthesis was raised by PDGF. Type analysis of collagen revealed substantial reduction of type IV collagen and relative increase of type V collagen in the PDGF-treated cells. By immunofluorescence study using anti-type IV collagen antibody, the lacework fluorescence was decreased with PDGF supplement. These findings indicate that PDGF induces the decrease of type IV collagen synthesis with the simultaneous diminution of basement membrane formation probably in association with phenotypic modulation of smooth muscle cells. PMID- 1423653 TI - A low molecular weight calf pineal peptide with an inhibiting effect on the growth of L1210 and HL60 cells. AB - The peptide isolated by us from calf pineal gland causes a reduction of RNA synthesis in vitro in L1210 and HL60 tumoral cells. This peptide also causes inhibition of cell proliferation; the cell viability is not modified. The effects are dose-dependent and reversible. PMID- 1423652 TI - Subcellular distribution of hydralazine in rat single vascular muscle cells. AB - High specific activity (20 Ci/mmol) tritiated hydralazine (3Hyd) distribution in isolated, cultured vascular muscle cells was determined to identify the sites of Hyd binding. 3Hyd dose-dependently bound to extracellular protein and to the area of organelles which secrete these proteins. Increased extracellular binding after Hyd pre-exposure suggests new binding sites may be exacerbated as a result of Hyd interactions. These experiments suggest a potentially important feature of the mechanism of action of this directly acting vasodilator. PMID- 1423654 TI - Proliferation of the MAC-T bovine mammary epithelial cell line in the presence of mammary secretion whey proteins. AB - Development of the MAC-T bovine mammary epithelial cell line by stable transfection with simian virus-40 large T-antigen should greatly assist study of possible intrinsic (local) and extrinsic (systemic) factors regulating bovine mammary epithelial cell development, differentiation, and function. This study evaluated the influence of mammary secretion whey proteins alpha-lactalbumin (ALA), beta-lactoglobulin (BLG), lactoferrin (LF), transferrin (TF) and serum albumin (SA) on MAC-T cell proliferation in the absence and presence of 10% fetal bovine serum (FBS). Concentration of whey proteins in culture ranged from 0 to 625 micrograms/ml. MAC-T cell proliferation in the absence of FBS was significantly lower than in the presence of 10% FBS. Alpha-lactalbumin and LF significantly decreased MAC-T proliferation in both the absence and presence of 10% FBS. Transferrin significantly increased MAC-T cell proliferation only in the absence of FBS. There were no significant differences in MAC-T cell proliferation cultured in the presence of BLG or SA. These experiments illustrate the potential usefulness of MAC-T cells for the study of factors involved in mammary cell proliferation. Results identified ALA, LF and TF as possible intrinsic factors associated with regulation of mammary epithelial cell proliferation. PMID- 1423655 TI - Simple method for isolation of primordial germ cells from chick embryos. AB - A simple one step centrifugation method was developed for purification of primordial germ cells (PGCs) of chick embryos. PGCs, constituting less than 0.1% of the total blood cells of stage 13-14 embryos that contained a microliter amount of blood, were concentrated at the interface of a 6.3% (w/v) and 14.4% (w/v) Ficoll bilayer by centrifugation at 800 x g for 30 min. the purity of these PGCs was 86%, which was 22 times that obtained previously. PMID- 1423656 TI - De novo biosynthesis and localization of immunoreactive inhibin (10.7 kDa) in normal human stomach. AB - We have previously reported the occurrence of inhibin-like peptide in gastric juice of normal men. In the present investigation, normal gastric mucosa was shown to synthesize inhibin, in vitro, as measured by 3H-leucine incorporation (Maximum at 18 h). Furthermore, the immunohistochemical localization studies demonstrated its presence in the acid secreting parietal cells and basal region of foveolar epithelium of gastric mucosa. Surprisingly, the protein secreting zymogen cells remained unstained. PMID- 1423657 TI - The involvement of Ca2+ and myosin light chain kinase in collagen-induced platelet activation. AB - In this study we have used several complementary biochemical and immunological techniques to examine the involvement of Ca2+ and myosin light chain kinase in collagen-induced platelet activation. Our results indicate that collagen stimulates a rapid influx of external Ca2+ (within the first 1-5 min of treatment) which is followed by phosphorylation of myosin light chains (within 10 min of treatment) and granule secretion (within 15 min of treatment). In addition, we have found that certain Ca2+ channel entry blockers (e.g. nifedipine and bepridil) or calmodulin antagonists (e.g. W-7) specifically inhibit collagen induced Ca2+ influx, myosin light chain phosphorylation and subsequent granule secretion. These data suggest that Ca2+/calmodulin-dependent myosin light chain kinase-mediated myosin light chain phosphorylation is necessary for regulating the actomyosin-related contractility required for normal platelet function. PMID- 1423658 TI - The effects of staurosporine and okadaic acid on baby hamster kidney fibroblast cell adhesion. AB - The effects of staurosporine, a potent protein kinase C inhibitor, and okadaic acid, a non-TPA tumour promoter, on the adhesion of BHK fibroblast were investigated. Staurosporine at 2.5 and 5 microM was found to stimulate a gradual increase in BHK cell adhesion as well as spreading in 3% serum-containing medium. An increase of approximately 27% over the control value was found at 5 microM concentration in 20 minutes. No such effect was seen in serum-free conditions. Staurosporine at 5 microM, enhanced BHK cell-cell adhesion in 3% serum and in serum-free conditions. Okadaic acid, a phosphatase inhibitor, at concentrations between 0.25 and 1 microgram/ml, was found to inhibit BHK cell-substratum adhesion and spreading. The inhibitory effect was time and concentration dependent. These findings suggest that protein kinase C might be involved in the mechanism(s) controlling BHK cell attachment. PMID- 1423659 TI - TGF-beta is a potent inhibitor of hepatocyte growth factor secretion by human fibroblasts. AB - Transforming growth factor-beta 1 (TGF-beta 1) inhibited secretion of human hepatocyte growth factor (hHGF), which is also known as scatter factor or fibroblast-derived tumor cytotoxic factor, by MRC-5 cells. The effect was detectable at as little as 10 pg/ml and was more potent than that of dexamethasone. Complete inhibition was observed after 12 h in the presence of 5 ng/ml of TGF-beta 1. Phorbol 12-myristate 13-acetate-induced secretion of hHGF from human skin fibroblasts was also suppressed by TGF-beta 1. TGF-beta 2 inhibited hHGF secretion by MRC-5 cells to the same extent as TGF-beta 1, but other growth factors such as epidermal growth factor and acidic and basic fibroblast growth factors had only a slight or null inhibitory effect. PMID- 1423660 TI - The ERE-like sequence from the promoter region of the testis specific hsp70 related gene is not estrogen responsive. AB - The 5'flanking region of the hsp70-related gene which is specifically expressed in rat and mouse spermatocytes contains the GGTCAnnnCGACC sequence closely resembling the palindromic consensus ERE (estrogen responsive element, GGTCAnnnTGACC). We used a transient expression assay to study whether this ERE like sequence can transfer estrogen responsiveness either to heterologous or homologous promoters linked to a reporter CAT gene. We found that the GGTCAnnnCGACC sequence either as an isolated element or in its natural sequence context does not respond to hormone stimulation in MCF-7 and Fe33 cells. This observation points to the importance of the T-nucleotide in a right half palindrome of ERE for ligand-dependent activation of transcription. PMID- 1423661 TI - Chromosome mal-orientation and reorientation during mitosis. AB - We argue that mal-orientation of mitotic chromosomes is not as rare as once believed. However, unlike bivalents during meiosis I, the reorientation of a mal oriented mitotic chromosome has yet to be observed. This appears to be due, in part, to the difficulty in differentiating mal-oriented chromosomes from mono oriented ones which are common during spindle formation in living mitotic cells. We assume that mitotic cells possess mechanisms for correcting chromosome mal orientations that are similar to those operating during meiosis. However, unlike meiosis, where reorientation appears to be triggered when tension on a K-fiber is relieved or reduced, other factors related to the close proximity of sister kinetochores may also induce reorientation in mal-oriented mitotic chromosomes. We favor a model in which the reorientation of a mitotic kinetochore depends on, and is initiated by, the kinetochore capturing MTs from the pole to which it is reorienting. PMID- 1423662 TI - Extension of filopodia by motor-dependent actin assembly. AB - A variety of mechanisms have been proposed to explain the forward extension of cytoplasm in advancing cells and axonal growth cones, including actin polymerization and osmotic swelling. Based on our observations of the filopodia of cultured neuronal growth cones, we propose a mechanism involving motor-induced extension and retraction. We observed that filopodia (actin-based protrusions 0.2 0.5 mu in diameter) extend and retract from growth cone lamellae at the same rate. Further, force is generated at the tips of filopodia which is sufficient to produce compressive buckling of the proximal portion of the filopodium. From our analysis of these movements we suggest that a motor protein powers both the extension and retraction of filopodia. PMID- 1423663 TI - Amino acid alterations in the benA (beta-tubulin) gene of Aspergillus nidulans that confer benomyl resistance. AB - We report the cloning and sequencing of 18 mutant alleles of the benA, beta tubulin gene of Aspergillus nidulans that confer resistance to the benzimidazole antifungal, antimicrotubule compounds benomyl, carbendazim, nocodazole, and thiabendazole. In 12 cases, amino acid 6 was changed from histidine to tyrosine or leucine. In four cases, amino acid 198 was changed from glutamic acid to aspartic acid, glutamine, or lysine. In two cases, amino acid 200 was altered from phenylalanine to tyrosine. These data, along with previous data indicating that amino acid 165 is involved in the binding of the R2 group of these compounds [Jung and Oakley, 1990: Cell Motil. Cytoskeleton 17:87-94], suggest that regions of beta-tubulin containing amino acids 6, 165, and 198-200 interact to form the binding site of benzimidazole antimicrotubule agents. These results also suggest that the presence of phenylalanine at amino acid 200 contributes to the great sensitivity of many fungi to benzimidazole antimicrotubule agents. PMID- 1423664 TI - Colchicine-sensitive and colchicine-insensitive intermediate filament systems distinguished by a new intermediate filament-associated protein, IFAP-70/280 kD. AB - A monoclonal antibody was produced, using as antigen a BHK-21 cytoskeletal preparation enriched in intermediate filaments (IF) and their associated proteins. This antibody reacted exclusively with a reproducible set of 70-280 kD polypeptides present in minor quantities in this preparation, as detected by immunoblot analysis. Based upon several criteria, this immunologically related group of polypeptides was designated as IFAP-70/280 kD (IF-Associated Protein): (1) it co-isolated with IF in vitro, (2) it co-localized (by both immunofluorescence and immunoelectron microscopy) with IF in situ in all stages of cell spreading, and (3) it segregated in vitro with the 54/55 kD (desmin/vimentin) structural IF subunit proteins of BHK cells through two cycles of in vitro disassembly/assembly. Immunogold labeling further localized IFAP 70/280 kD to regions of parallel or loosely bundled IF in situ, suggesting a role in regulating the supramolecular organization of IF. When this monoclonal antibody was used for double-label immunofluorescence observations of colchicine treated BHK cells, it demonstrated the presence of colchicine-sensitive and colchicine-insensitive IF. Anti-IFAP-70/280 kD localized entirely to the drug induced juxtanuclear IF cap, while a polyclonal antibody directed against the desmin/vimentin structural IF subunits and the previously characterized monoclonal anti-IFAP-300 kD [Yang et al., 1985; J. Cell Biol. 100:620] localized to both the juxtanuclear IF cap and a colchicine-insensitive IF network peripheral to the cap in the same cells. The colchicine-insensitive IF pattern often exhibited similarities to that observed for the actin-based stress fiber system, suggesting that stress fiber association may be an additional factor in IF organization. PMID- 1423665 TI - Ca(2+)-regulated actin and phospholipid binding protein (68 kD-protein) from bovine liver: identification as a homologue for annexin VI and intracellular localization. AB - An F-actin binding protein was purified from bovine liver by means of DNase I affinity, hydroxylapatite and DEAE-cellulose column chromatographies. It consisted of a single polypeptide chain having an apparent molecular weight of 68,000 with a Stokes radius of 35 A. Electron microscopy of rotary shadowed specimens showed that the 68 kD protein is a globular protein. This protein showed a higher affinity for F-actin in the presence of Ca2+ than in its absence, which is opposite to the actin-binding property shown by nonmuscle alpha-actinin or fimbrin. The 68 kD protein had no F-actin severing and capping activity. Interestingly, the 68 kD protein was found to aggregate liposomes at micromolar Ca2+ concentrations. Immunoblot analysis and partial protein sequence data identified the 68 kD protein as an annexin VI (p68) homologue. Immunocytochemical studies showed that the 68 kD protein was localized along stress fibers as well as membrane ruffles, microspikes and focal contacts, raising the possibility that annexin VI may contribute to control membrane-microfilament interaction in the cell. PMID- 1423666 TI - Three-dimensional motility cycle in leukocytes. AB - A 3-dimensional dynamic image analyzing system (3D-DIAS) has been developed in which a translocating cell is optically sectioned in the z-axis within a 2 sec period; the perimeter of the cell in each section is digitized into the 3D-DIAS data file, and the digitized perimeters are wrapped in order to reconstruct the cell image in three dimensions. Using 3D-DIAS, we have obtained the first dynamic 3-dimensional description of human polymorphonuclear leukocytes (PMN) translocating on a glass surface. A general behavior cycle has emerged which includes two phases. In the first, an ellipsoidal PMN with significant z-axis extends anteriorly and descends to the substratum. When the ventral surface of the anterior end contacts the substratum, there is rapid anterior expansion, which correlates with velocity peaks. In the second phase, the elongate PMN stops translocating along the substratum, the anterior end lifts off of the substratum, sometimes to heights greater than the length of the PMN at the substratum, and finally the PMN retracts into an ellipsoidal morphology still capable of random protrusions. During this second phase, which correlates with velocity troughs, turning usually occurs. The degree of turning is restricted by the continuous integrity of the posterior uropod. The period of the behavior cycle varies from roughly 0.5 to 2 min between PMNs, but is relatively constant within each individual PMN. PMID- 1423667 TI - Classification of temporomandibular joint osteoarthrosis and internal derangement. 2. Specific diagnostic criteria. AB - Separate entities of temporomandibular joint osteoarthrosis and internal derangement are operationally defined. Criteria are based on an analysis of the diagnostic significance of symptoms and signs, principles of synovial joint pathology in general, and on therapeutic considerations. The primary goal was to enable identification of characteristic stages of osteoarthrosis and internal derangement using diagnostic tools readily available in practice. PMID- 1423668 TI - Temporomandibular-related pressure thresholds: a model for establishing baselines. AB - The use of pressure threshold measurement to quantify tender spots and trigger points in muscles is well established. Its application to the field of temporomandibular disorders, however, has been more recent and less widely published. Pressure threshold measurement may be useful to define values for dysfunctional muscles or structures so that changes in muscle condition through a course of treatment can be quantified. Normal values for many muscles in the body have been established, but studies of this type in the masticatory system are limited and have often used a fixed, pre-determined pressure cutoff, rather than measuring thresholds across a number of patients. This pilot study seeks to determine whether normal values exist for the anterior temporalis muscles, the masseter muscles, and the lateral capsules of the temporomandibular joints. Intrarater and interrater reliability in measuring thresholds was also studied with the aim of contributing toward a methodological model for further study. PMID- 1423669 TI - Tinnitus of TMJ origin: a preliminary report. AB - Twenty patients whose chief complaint was tinnitus were examined. They were not known to have temporomandibular disorders. They did not have pain or dysfunction. They were examined by physicians for ear disorders and the results were considered negative. Each of these patients had a complete history and clinical temporomandibular joint examination. The clinical examination included muscle and joint palpation and stethoscopic examination of the joint. This examination also included selected computerized mandibular scans and electromyographic studies of selected facial muscles. Each subject had eight views of transcranial lateral oblique x-rays taken. It was determined that 19 of these individuals had one or more clinical, electromyographic, and radiographic indications of a temporomandibular disorder. From this study, it appears that individuals who have tinnitus with no apparent otologic basis for this symptom should have a careful evaluation of the temporomandibular apparatus. A temporomandibular disorder may be one of the primary causes of this symptom. PMID- 1423670 TI - Physical therapy post-arthroscopic TMJ management (update). AB - Arthroscopic surgery of the temporomandibular joint is now being widely used for therapeutic, rather than diagnostic, benefits. However, there still remains a void in the literature as to the various rehabilitative protocols used on those patients who have undergone arthroscopy. This article presents a revision of techniques and procedures in the treatment and postoperative management of arthroscopic cases. This revision has been written after five years of experience and the treatment of approximately 300 cases. PMID- 1423671 TI - Physical therapy evaluation of the craniomandibular pain and dysfunction patient. AB - This article offers an evaluation form to evaluate the craniomandibular pain and dysfunction patient. This form combines dental and physical therapy evaluation components in a two-page format that is quick and easy to use. By using this form physical therapists are able to determine the problem list, develop the treatment plan, and establish excellent communication between the patient, therapist, and dentist. PMID- 1423672 TI - Contribution of oral habits to dental disorders. AB - Oral habits or parafunction may contribute to dental, periodontal, or neuromuscular damage. Such habits, of which the patient is often unaware, may cause considerable damage. Habits may be occlusal or non-occlusal, and may affect the dentition and/or the oral soft tissues. Drawing a patient's attention to the damage caused by some habits of which he or she is unaware often leads to cessation, whereas with certain conscious habits, such as nail or finger biting, success is much more limited. PMID- 1423673 TI - A comparative study of three therapeutic modalities in a temporomandibular disorder (TMD) population. AB - A comparative study of three treatment modalities, pharmacologic, occlusal appliance, and their combined use, was conducted to test their therapeutic efficacy on 61 temporomandibular disorder (TMD) patients. Alprazolam (Xanax) was used for the pharmacologic treatment; the occlusal appliance therapy consisted of a flat maxillary stabilization splint. Of the 61 patients, 19 received Alprazolam, 30 received occlusal appliance therapy, and 12 received combined therapy. Subjects were examined at two-week intervals for two months. Only 42 patients attended all follow-up visits. Eight parameters were studied: severity of pain, periodicity of pain, self-evaluated stress, muscle sensitivity to palpation, joint sensitivity to palpation, joint noises, limitation of opening, and limitation of lateral movement. No significant difference was found between the treatment modalities for most of the parameters. All three proved to be effective. Alprazolam increased the restricted mandibular movement, was least effective on joint sensitivity to palpation, and had no effect on joint noises. The combined treatment approach not only failed to prove superior to the other treatments, but showed less improvement in some parameters, possibly due to the small sample. PMID- 1423674 TI - Organization and patient flow in an urban musculoskeletal dysfunction clinic. AB - A comprehensive clinic for treatment of a variety of musculoskeletal disorders is examined from several points of view. This clinic, affiliated with a comprehensive health sciences university and located in a tertiary medical center, affords efficient access to a variety of health care specialties and subspecialties. Patient sources, severity of dysfunction, and typical patient flow are analyzed in order to describe the clinic's functions. PMID- 1423675 TI - TMJ disorders--a perspective for the nineties. PMID- 1423676 TI - Multivariate analysis of craniomandibular disorders. AB - This article presents the clinical application of a special statistical method, the Multiple Correspondence Analysis (MCA), derived from data analysis and particularly suited to study a restricted population (here, 202 patients with temporomandibular joint [TMJ] disorders) whose characteristics are defined by a large number of modalities (140). Processing of a Burt-type data table, or Complete Disjunctive Table (CDT), provided a geometrical visualization of information, and permitted determination of the prevalent factor axes. Results showed a significant relationship between all the articular disorders, either peripheral or focal (TMJ), thus revealing the possibility of a yet, little known morphogenic influence on the genesis of TMJ disorders. PMID- 1423677 TI - Classification of temporomandibular joint osteoarthrosis and internal derangement. 1. Diagnostic significance of clinical and radiographic symptoms and signs. AB - In the clinical setting, diagnosis primarily depends on the history and present status of the patient, and on the examiner's expertise in physical examination and interpretation of conventional radiographs. In order to evaluate the diagnostic significance of clinical and radiographic variables, the authors used magnetic resonance imaging as the 'golden standard' for articular disk position. A total of 90 temporomandibular joints (TMJs) were available for the study. Group I (representing 'normal' disk position) comprised eight joints (8.9%); group II (representing reducing disk), 34 joints (37.8%); and group III (non-reducing disk), 48 joints (53.3%). Nine anamnestic, 15 clinical, and three radiographic variables obeyed pre-defined univariate selection criteria. Relatively high sensitivities were found for clicking-related variables in MR-group II, and for variables related to movement restriction in MR-group III. None of the symptoms or signs appeared to be pathognomonic for either one of the diagnostic groups. Principal component analysis revealed 13 factors that could be grouped into three major categories, representing impairment of joint mechanics, joint pain and tenderness, and radiographically detectable degenerative changes, respectively. Discriminant analyses showed that symptom combinations, which included clinical variables related to joint mechanics, appeared to provide the most useful diagnostic information. It is concluded that reducing and permanent disk displacement can be distinguished in many cases using clinical and radiographic variables. However, there is considerable variability within these groups. To establish a specific clinical diagnosis, a more detailed classification of osteoarthrosis and internal derangement is desirable. PMID- 1423678 TI - Physical therapy not modalities for craniomandibular disorders. PMID- 1423679 TI - Head posture and cervicovertebral and craniofacial morphology in patients with craniomandibular dysfunction. AB - A relationship between particular characteristics of dental occlusion and craniomandibular disorders (CMD) has been reported, while less attention has been focused on the possible effect of dysfunction of the masticatory system on head posture or cervicovertebral and craniofacial morphology. Natural head position roentgen-cephalograms of 16 young adults with complete dentition taken before and after stomatognathic treatment displayed an extended head posture, smaller size of the uppermost cervical vertebrae, decreased posterior to anterior face height ratio, and a flattened cranial base as compared with age- and sex-matched healthy controls. The lordosis of the cervical spine straightened after stomatognathic treatment. The results are an indication of the close interrelationship between the masticatory muscle system and the muscles supporting the head, and lead to speculation on the principles of treating craniomandibular disorders. PMID- 1423680 TI - Superficial vascularity of temporomandibular joint retrodiskal tissue: an element of the internal derangement process. AB - Superficial vascular changes in the retrodiskal tissue are an aspect of the remodeling process during progressive anterior displacement of the temporomandibular joint (TMJ) disk. The salient portion of the remodeled retrodiskal tissue (RRT) is contained in a 3 x 3 grid of arthroscopic fields in the superior joint space, plus the tympanic portion of the remodeled retrodiskal tissue. A four-level vascularity classification system gives a statistically significant association between superficial avascularity of the remodeled retrodiskal tissue and progressive stages of disk derangement. In particular, simultaneous avascularity in both the tympanic remodeled retrodiskal tissue and the central arthroscopic field occurs with severe disk displacement without reduction. Analyses are based on 16 microscopic studies, 25 magnetic resonance imaging and tomographic imaging studies, and 26 arthroscopic studies. PMID- 1423681 TI - Development of alloplastic materials for temporomandibular joint prosthesis: a historical perspective with clinical illustrations. AB - This paper gives the history of the development of alloplastic materials presently used in the temporomandibular joint (TMJ). It discusses the evaluation of TMJ implants, from those being used primarily for ankylosis to the more varied and sophisticated implant designs used today. There is a discussion on the treatment of osteoarthritis with implants and also a discussion on the use of TMJ implants to repair skeletal and dental malrelationships, primarily anterior open bites. Included is a presentation of the latest research by Schellhas et al., which establishes that previously undiagnosed organic disease in the joint proper is a common cause of skeletal and dental malrelationships and that TMJ disease can cause malocclusion. PMID- 1423682 TI - Surgical treatment of temporomandibular joints in patients with chronic arthritic disease: preoperative findings and one-year follow-up. AB - Twenty-nine temporomandibular joints (TMJs) in 19 patients with chronic arthritic disease were surgically treated. Nine patients had rheumatoid arthritis (including two with juvenile type), six had ankylosing spondylitis and four had psoriatic arthropathy. Using a preauricular approach, diskectomies with synovectomies were performed in 23 joints (14 patients) with chronic arthritic abnormalities. Diskectomies without synovectomies were performed in six joints (five patients), which proved to have internal derangements unrelated to their chronic arthritic disease. Joints with chronic arthritis showed considerable variation in inflammatory reactions, but were characterized by increased vascularization, synovial proliferation to the articulating surfaces and mostly pannus formation and bone resorption. A response in pain relief was seen in 85% of the patients three months postoperatively and in 79% of the patients 12 months postoperatively, indicating that diskectomy with synovectomy may be favorable in patients with severe TMJ problems due to involvement of chronic arthritic disease. PMID- 1423683 TI - Postoperative physical therapy in temporomandibular joint arthroplasty. AB - This article offers a revised physical therapy treatment approach for rehabilitating a temporomandibular joint (TMJ) following arthroplastic surgical intervention. Surgical repair is only advised in those chronic cases where refractory symptoms affect the quality of the patient's life and prevent patients from carrying out their normal daily activities. Previous nonsurgical and surgical management usually fails to correct the problem in these types of cases. Rehabilitation guidelines discussed include plication, diskectomy (with or without interpositional implant), costochondral graft, fossa implant, and total joint replacement. PMID- 1423684 TI - Temporomandibular joint osteoarthrosis and generalized joint hypermobility. AB - Peripheral joint mobility of temporomandibular joint (TMJ) osteoarthrosis and internal derangement patients (n = 25) and of a control group (n = 29) was measured according to a rigidly standardized protocol, in order to study the relationships between TMJ osteoarthrosis and internal derangement and generalized joint hypermobility. No significant differences in peripheral joint mobility between the two groups were found. Therefore, generalized joint hypermobility cannot be considered as a predisposing factor for TMJ osteoarthrosis. PMID- 1423685 TI - A simple questionnaire and clinical examination to help identify possible non craniomandibular disorders that may influence a patient's CMD symptoms. AB - A patient with craniomandibular disorder (CMD) symptoms may have CMD, a local or systemic disorder that mimics CMD, or CMD superimposed with a local or systemic disorder that exacerbates the CMD symptoms. When evaluating a patient with CMD symptoms, the practitioner needs to determine whether local or systemic problems contribute to the patient's symptoms. The author presents a simple questionnaire that can help identify some non-CMD problems that may contribute to the patient's symptoms. A discussion of each question and examples of possible non-CMD disorders are provided. The author also describes a clinical examination that may be used in conjunction with the questionnaire to help identify some non-CMD conditions. PMID- 1423686 TI - Conservative and successful treatment of temporomandibular dysfunction in a private rural practice. AB - This clinical study of 382 patients with temporomandibular dysfunction (TMD) details how successful treatment can be achieved in a rural area without the support and services of specialized TMD clinics. Successful treatment is within the scope of the general dentist, provided the practitioner understands the patient's total problem and treatment options. The study spanned a 10-year period, including follow-up at one, five, and eight-year intervals. PMID- 1423687 TI - Musicians and temporomandibular disorders: prevalence and occupational etiologic considerations. AB - Temporomandibular dysfunction (TMD) appears to be a significant problem affecting musicians. While the incidence of TMD symptoms for musicians is similar to that of the general population, these symptoms are activated and accentuated when performing or practicing. TMD symptoms appear to be significant in trombone, trumpet, tuba, violin, and viola musicians. It is the author's opinion that vocalists are also significantly affected by TMD. Preliminary results of a survey in progress relative to TMD and the singing voice are reported. PMID- 1423688 TI - Case report of trigeminal neuralgia presenting as odontalgia. AB - A case of trigeminal neuralgia presenting as odontalgia in a 47-year-old female is described. This case shows the difficulty of making a correct diagnosis and how patients can be subjected to unnecessary treatment and continued suffering when a correct diagnosis is not made. PMID- 1423689 TI - Facial skeleton remodeling due to temporomandibular joint degeneration: an imaging study of 100 patients. AB - One hundred patients with recently acquired, externally visible mandibular deformity and no history of previous extraarticular mandible fracture were selected for retrospective analysis. All had been investigated clinically and with radiography, tomography, and high-field surface-coil MR imaging to determine the presence or absence and extent of temporomandibular joint degeneration. Temporomandibular joint degeneration was found in either one or both joints of each patient studied. Chin deviation was always toward the smaller mandibular condyle or more diseased joint, and many patients either complained of or exhibited malocclusion, often manifested by unstable or fluctuating occlusion disturbances. Three radiologically distinct forms of degenerative vs adaptive osteocartilaginous processes--(1) osteoarthritis, (2) avascular necrosis, and (3) regressive remodeling--involving the mandibular condyle and temporal bone were identified in joints most often exhibiting meniscus derangement. Osteoarthritis and avascular necrosis of the mandibular condyle and temporal bone were generally associated with pain, mechanical joint symptoms, and occlusion disturbances. Regressive remodeling was less frequently associated with occlusion disturbances, despite remodeling of the facial skeleton, and appears to result from regional osteoporosis. Forty patients (52 joints) underwent open arthroplasty procedures, including either meniscectomy or microsurgical meniscus repair, at which time major radiologic diagnoses were confirmed. Surgical and pathologic findings included meniscus displacement, disk degeneration, synovitis, joint effusion, articular cartilage erosion, cartilage healing/fibrosis, cartilage hypertrophy, osseous sclerosis, osteophyte formation, osteochondritis dissecans, localized or extensive avascular necrosis, and decreased mandibular condyle mass and vertical dimension. We conclude that temporomandibular joint degeneration is the principal cause of both acquired facial skeleton remodeling and unstable occlusion in patients with intact dentition and without previous mandible fracture. PMID- 1423690 TI - Pharmacological treatment of facial pain. PMID- 1423691 TI - A commentary on methods in peptide neurobiology: focus on neurotensin. AB - Research into the identification and functional role of neuropeptides has taken a prominent place in the field of neurobiology within the past 15 years. The type of knowledge available concerning these compounds is, by necessity, limited by the experimental methods currently in use. In this manuscript, an overview is provided of several types of experimental procedures that have been used to study neuropeptide actions in the central nervous system (CNS) and details are presented of the specific application of these procedures as they have been used in the authors' laboratories to study the physiological role of the endogenous brain/gut tridecapeptide neurotensin. The methods were chosen to illustrate research strategies for examining various aspects of peptide neurobiology and include radioimmunoassay (peptide content), high-performance liquid chromatography (HPLC) (analysis of peptide and its fragments), protein phosphorylation (signal transduction), and behavior. Although by no means inclusive, it is the authors' hope that the reader may be able to apply these methods to their own research as well as gain an appreciation for the distance that yet remains on the journey into dissecting the function and physiology of CNS peptides. PMID- 1423692 TI - Vasopressin involvement in antipyresis, social communication, and social recognition: a synthesis. AB - This review concentrates on the sexually dimorphic neuronal cells and fibers that contain arginine-vasopressin (AVP) and are present in several extrahypothalamic brain areas besides the neurohypophyseal system. Of particular interest are the vasopressinergic neurons that project from the bed nucleus of the stria terminalis and the medial amygdala to the lateral septum because their content of vasopressin is a positive function of circulating levels of testosterone. Physiological and behavioral data suggest that androgen-dependent vasopressin plays an important role in antipyresis and social recognition. In addition, there is evidence that extrahypothalamic AVP-sensitive neurons and hypothalamic AVP containing neurons control scent marking, a form of social communication in hamsters, in a sex-dependent manner. The interrelationships of these different functions of brain vasopressin are discussed. PMID- 1423693 TI - The surgical treatment of tendinitis. Clinical rationale and biologic basis. AB - The rationale for surgical treatment of tendinitis is to induce a modulation of the tendon cell-matrix environment by either promoting a renewed wound repair cycle or by the removal of aberrant tissue. The adequacy of healing as a result of surgical tendon treatment has been poorly documented histologically; what evidence exists suggests normal tissue is not achieved. The clinical experience of the authors as well as preliminary analysis of wound healing patterns in a longitudinal internal tenotomy rabbit tendo-Achilles model are discussed. PMID- 1423694 TI - Overuse injuries to tendons and apophyses in children and adolescents. AB - Overuse injuries to tendons and apophyses are being seen with increasing frequency in children and adolescents as they increase their participation in organized sports, fitness, and dance activities. A retrospective review of 724 overuse tendon and apophyseal injuries seen in the Sports Medicine Clinic at the Boston Children's Hospital suggested that growth and maturation constitute additional risk factors for injury occurrence. Diagnosis and treatment of these injuries is discussed in the context of sports participation. PMID- 1423695 TI - Complete Achilles tendon ruptures. AB - Achilles tendon ruptures can be treated nonsurgically in the nonathletic or low end recreational athletic patient, particularly those more than 50 years of age, provided the treating physician does not delay in the diagnosis and treatment (preferably less than 48 hrs and possibly less than 1 week). The patient should be advised of the higher incidence of re-rupture of the tendon when treated nonsurgically. Surgical treatment is recommended for patients who are young and athletic. This is particularly true because the major criticism of surgical treatment has been the complication rate, which has decreased to a low level and to a mild degree, usually not significantly affecting the repair over time. Surgical treatment in these individuals seems to be superior not only in regard to re-rupture but also in assuring the correct apposition of the tendon ends and in placing the necessary tension on the tendon to secure appropriate orientation of the collagen fibers. This in turn allows them to regain full strength, power, endurance, and an early return to sports. Surgery is also recommended for late diagnosed ruptures where there is significant lengthening of the tendon. Surgical technique should involve a medial incision to avoid the sural nerve, absorbable suture, and augmentation with fascia or tendon where there is a gap or late rupture. Postoperatively, the immobilization should be 7 to 10 days in a splint. A walking boot with early motion in plantar flexion or a short leg cast with the tendon under slight tension should thereafter be used for 4 to 5 weeks. An early and well-supervised rehabilitation program should be initiated to restore the patient to the preinjury activity level. PMID- 1423696 TI - Partial Achilles tendon tears. AB - Persistent pain in the Achilles tendon is often caused by partial ruptures leading to a hypoxic state in the tissues, insufficient healing, and a remaining, immature, and painful scar. The rupture is caused by overuse and conservatively treated with orthotic devices to reduce tendon load and physiotherapy to correct training errors and strength the muscle-tendon unit. Significant partial ruptures seem to respond poorly to conservative measures and do not improve with time. Surgical treatment with excision of degenerated tissue which leads to complete pain relief and full restoration of function with long-standing effects in most cases is why persistent Achilles tendon pain due to partial rupture preferably should be treated surgically. PMID- 1423697 TI - Achilles tendon overuse injuries. AB - Overuse injuries of the Achilles tendon are common in patients engaging in recreational athletics. Achilles tendon overuse injuries exist as a spectrum of diseases ranging from inflammation of the paratendinous tissue (paratenonitis), to structural degeneration of the tendon (tendinosis), and finally tendon rupture. Factors known to predispose patients to Achilles tendinitis include inadequate stretching, training errors, mechanical malalignment of the lower extremities, rigid training surfaces, and occasionally systemic disease. Treatment of the patient with paratenonitis and tendinosis is initially conservative, emphasizing passive stretching, concentric and eccentric strengthening, correction of training errors, and restoration of normal limb alignment. Patients resistant to this protocol often exhibit a more advanced degree of tendon change. A high percentage of these patients can benefit from surgical debridement of the involved tendon, and they can anticipate successful return to recreational athletics. Steroid injections should not be routinely used in patients with Achilles tendinitis. Rupture of the Achilles tendon following intratendinous injection has been reported. PMID- 1423699 TI - Patellar tendon injuries. AB - Patellar tendon injury secondary to overuse represents a failure of soft tissue healing that can lead to chronic symptoms. Clinical staging of this process is helpful in the initial management. Diagnostic imaging can help define the character of the injury as well as localized pathology. Initial treatment of clinical stages I, II, and III is conservative. PMID- 1423698 TI - Injuries at the myotendinous junction. AB - The complete role of the myotendinous junction is discussed in this article. The morphology and function of the junction, typical injuries occurring at this region, delayed-onset muscle soreness, and muscle strain injury are described. Muscle strain injury is covered in detail, including characterization, treatment, and prevention. Clinical information is conveyed as well as basic science study results pertinent to the clinical situation. PMID- 1423700 TI - Tendon and muscle injuries in the groin area. AB - Groin injuries in athletes are being recognized as one of the most difficult problems in sport. The symptoms associated with chronic groin injuries are often diffuse and uncharacteristic. These injuries usually constitute a major diagnostic and therapeutic challenge, the success of which depends on a correct diagnosis. It is necessary to establish a broad, differential background, and therefore, this article includes a broad description of groin injuries. PMID- 1423701 TI - Hand tendon injuries in athletics. AB - Hand tendon injuries may be caused by acute trauma or chronic overuse. Although these injuries are common in athletics, specific diagnoses can be difficult to make and are often delayed. Early diagnosis is the key to a good outcome. Most hand tendon injuries do well with nonoperative treatment when initiated early. Long-term disruption of the delicate balance of muscle forces in the hand will lead to secondary changes that are often difficult to correct. Delay in treatment of overuse injuries may produce chronic inflammation that does not respond to conservative care and requires operative management. A sound knowledge of hand anatomy, awareness of the differential diagnosis, and a high index of suspicion are needed for proper care of the athletic hand injury. PMID- 1423702 TI - Elbow tendinosis/tennis elbow. AB - The histology of pathologic tennis elbow tissue reveals noninflammatory tissue, thus the term angio-fibroblastic tendinosis. The goal of nonsurgical treatment is a revascularization and collagen repair of this pathologic tissue by rehabilitative exercise. In the event of rehabilitation failure, surgical correction by removal of this pathologic tissue is the surgical technique of choice. PMID- 1423703 TI - Shoulder tendinoses. AB - The most common source of shoulder pain is soft-tissue dysfunction. Although fractures of the humerus, scapula, and clavicle are common throughout life, most problems encountered between the ages of 15 and 60 are related to the ligaments, tendons, and muscles of the shoulder girdle. This article deals mainly with tendinitis and tendinosis as primary entities, and to a lesser extent with tendon problems attributable to a primarily bony or ligamentous dysfunction. PMID- 1423704 TI - [The status of children and family relations after successful in vitro fertilization and embryo transfer]. AB - Using a retrospective questionnaire method, the authors evaluated the neuropsychologic status of 20 IVF children and the family relationships. The status of the children is favourable and in certain activities (composition of sentences) the children were better than their peers. According to the authors this is due to the increased care of mature parents after the arrival of the long expected child. The authors confirmed on their own material that the birth of an IVF child has a far reaching positive biological, psychological and social impact on both parents and training of their children. If the family environment was influenced by long lasting treatment of sterility, the arrival of an IVF child normalizes the situation. PMID- 1423705 TI - [Personal experience with colpoureteral suspension using the Burch method]. AB - The objective of the work was to evaluate one approach of evaluation of the effect achieved by the mentioned corrective operation, i.e. the subjective evaluation by the patients themselves. In order to ensure comparability of evaluation at different time intervals, the authors used a questionnaire with 13 questions focused on continence and changes of micturition as well as on sexual aspects and changes in the social sphere. Sixty-nine patients were at least one year after operation. Evaluation 6 weeks after operation was implemented in 105 patients. The subjective sensation of complete recovery and satisfaction with treatment in 93.33% after six weeks and 94.20% after one year with minimal complaints regarding micturition indicates that the operation sec. Burch is a very good corrective operation, resolving stress incontinence of urine in women. PMID- 1423706 TI - [Evaluation of the analgesic effect of dolsin during labor]. AB - The authors evaluate the analgetic action of 50 mg dolsin in parturient women during childbirth using a Slovak version of McGill's questionnaire on pain. The intensity of pain in women is evaluated before administration of dolsin and after its administration. The obtained data on the analgetic effect are compared with the total score of pain and individual components of pain by the paired t-test. Although the mean values of the total score of pain and the sensory components of pain declined after administration of dolsin, the change was not statistically significant. In the affective component of pain the mean value of PRI(A) increased after dolsin administration. PMID- 1423707 TI - [Vaginal adenosis and problems in its treatment]. AB - The authors investigated four patients with suspected vaginal adenosis without prenatal exposure to DES. Adenosis was confirmed by histological examination in two instances. In one case the adenosis was formed by glands of the endometrial type. In the second case it was formed by glands of the endocervical type with atypical features. On check-up biopsy an adenocarcinoma was revealed (non-light cell) resembling morphologically a cervical adenocarcinoma. The authors discuss the embryogenesis, histogenesis, epidemiology and differential diagnosis of adenosis. At the same time the authors reflect on problems of its therapy. Finally the authors summarize some practical recommendations for diagnostic and therapeutic purposes. PMID- 1423708 TI - [Personal experience with surgical treatment of urinary incontinence in women]. PMID- 1423709 TI - [Use of a pessary for bloodless cerclage for cervical insufficiency in pregnant women--25 years' experience]. PMID- 1423710 TI - [An effective composite spasmo-analgesic, Algifen--results of a clinical trial in gynecology]. PMID- 1423711 TI - [Radical surgery in endometrial carcinoma]. PMID- 1423712 TI - [Effective prevention and therapy of premature labor]. PMID- 1423713 TI - [Relation between diet and certain types of diseases in nations with high living standards--hormonal and biochemical mechanisms]. PMID- 1423714 TI - [Additional effects of steroids and peptide hormones during pregnancy according to Hill]. PMID- 1423715 TI - [History of maternal care in Czechoslovakia. I]. PMID- 1423716 TI - A single amino-acid change in the iron-sulphur protein subunit of succinate dehydrogenase confers resistance to carboxin in Ustilago maydis. AB - The sequence of an allele encoding the iron-sulphur protein (Ip) subunit of succinate dehydrogenase (Sdh) was determined following PCR amplification of genomic DNA from a carboxin (Cbx)-sensitive Ustilago maydis strain. Comparison of this sequence with that of the Ip allele from a Cbx-resistant strain (IPr) revealed a two-base difference between the sequences. This mutation led to the substitution of a leucine residue for a histidine residue within the third cysteine-rich cluster of the deduced amino-acid sequence of the Ipr allele. This cluster, which is associated with the S3 iron-redox centre, is involved in the transport of electrons from succinate to ubiquinone (Q). Confirmation that this nucleotide change led to enhanced resistance to Cbx was obtained following mutagenesis of the sensitive Ip allele to the resistant form and expression of the mutated allele in U. maydis. PMID- 1423717 TI - Organization of ATPA coding and 3' flanking sequences associated with cytoplasmic male sterility in Phaseolus vulgaris L. AB - A region of the mitochondrial genome associated with cytoplasmic male sterility (CMS) in Phaseolus vulgaris was flanked by two different repeated sequences designated x and y. The DNA sequence of the CMS-unique region and a portion of each flanking repeat was determined. Repeat x contained a complete coding copy of the F1 ATPase subunit A (atpA) gene, as well as an open reading frame (orf) predicting a protein of 209 amino acids. The TGA termination codon of the atpA gene and the ATG initiation codon of orf209 were overlapping. These reading frames were oriented with their 3' ends proximal to the CMS-unique region. The CMS-unique region of 3736 nucleotides contained numerous orfs. The longest of these predicted proteins being of 239, 98 and 97 amino acids. The 3' coding and 3' flanking regions of orf98 were derived from an internal region of the higher plant chloroplast tRNA alanine intron. The region of repeat y immediately adjacent to the CMS-unique region contained the 111 carboxy-terminal coding residues of the apocytochrome b (cob) gene. This segment was oriented with its 5' end proximal to the CMS-unique region, but cob gene sequences were not fused to an initiation codon within the unique region. PMID- 1423718 TI - Involvement of a large inverted repeated sequence in a recombinational rearrangement of the mitochondrial genome of the higher fungus Agrocybe aegerita. AB - Southern hybridization of the total DNA of Agrocybe aegerita with cloned mitochondrial (mt) probes revealed a sequence homology between two distant mitochondrial restriction fragments. From the mtDNA restriction map and the distribution of restriction sites on the cross-hybridizing mitochondrial fragments, two copies of a large inverted repeated sequence (IR) of 3 kbp were located on the mitochondrial genome. These IR sequences divided the 80 kbp mtDNA into two single-copy regions of 24 kbp (SSC) and 50 kbp (LSC). For the first time in higher fungi, this IR sequence has been shown to be involved in an intramolecular homologous recombinational event. Such a rearrangement led to an inversion of the orientation of the two unique-copy regions, without any change in mtDNA complexity. The location of the recombinational event was compared with previously reported plant and fungal mitochondrial rearrangements and the potential role of the IR sequence was discussed. PMID- 1423719 TI - Cell type determines plastid transmission in tomato intergeneric somatic hybrids. AB - Mesophyll (M)- and suspension culture (S)-derived protoplasts of both Lycopersicon esculentum, tomato, and its wild relative Solanum lycopersicoides were fused as S + M, M + M and S + S combinations, respectively, to resolve the role of parental cell types in determining cpDNA transmission to intergeneric somatic hybrid plants. The mesophyll cpDNA was preferentially transmitted to 96% of the plants, each regenerated from a separate callus, in M + S and S + M fusion combinations. In contrast, for the M + M combination there was an equable distribution of either tomato cpDNA or that of S. lycopersicoides among the 34 hybrid plants. The number of plastids or proplastids in mesophyll or suspension protoplasts was not a factor regulating cpDNA transmission. Mesophyll or suspension protoplasts of both fusion partners had comparable frequencies of either plastid type with a mean of 23. The biased transmission of plastids from the mesophyll parent in somatic hybrid plants of S + M and M + S combinations appears to be due to differential multiplication of plastids, possibly conditioned by an unequal input of the nucleoids found in plastids versus proplastids. In the M + M fusion, plastid and nucleotide input and subsequent plastid multiplication are apparently equal, and when combined with random sorting out leads to an equal distribution of parental cpDNAs in the regenerated somatic hybrid plants. For the S+S combination, 22 somatic hybrid plants have exclusively tomato cpDNA, an outcome that is not readily explained by donor cell input. PMID- 1423720 TI - Rubisco spacer sequence divergence in the rhodophyte alga Gracilaria verrucosa and closely related species. PMID- 1423721 TI - DNA translocations contribute to chromosome length polymorphisms in Candida albicans. AB - Rotating-gel electrophoresis and DNA hybridization were used to compare the electrophoretic karyotype of six Candida albicans isolates. The hybridization pattern for 22 cloned sequences, including eight previously unmapped genes, indicates that there are eight pair of homologous chromosomes in each strain. However, since homologous chromosomes can differ in length, it is possible to resolve more than eight bands in some strains. The mapping data demonstrate that linkage groups are generally conserved suggesting that, in spite of gross karyotype differences, there is an underlying similarity in the genome organization of different isolates. The hybridization data also provide direct evidence that DNA translocations and reciprocal translocations contribute to chromosome length polymorphisms in C. albicans. PMID- 1423723 TI - Enhanced stability of YEp plasmids in lager brewing yeasts is related to lager brewing yeast 2-microns DNA. AB - YEp plasmid stability in the presence of either Saccharomyces cerevisiae laboratory strain 2-microns DNA, or lager brewing yeast 2-microns DNA in the same genetic background, was compared under non-selective culture conditions. It was found that YEp plasmids were more stably maintained in the presence of lager 2 microns DNA under these conditions. By construction of laboratory-lager 2-microns DNA hybrid plasmids, an 867 bp StuI fragment of lager 2-microns DNA was shown to be responsible for the enhanced stability of the YEp plasmid. Nucleotide substitutions at two sites were found by sequencing this region. It was also confirmed that increasing cell ploidy enhanced YEp stability under non-selective conditions. PMID- 1423722 TI - Complementation of Saccharomyces cerevisiae acid phosphatase mutation by a genomic sequence from the yeast Yarrowia lipolytica identifies a new phosphatase. AB - A Yarrowia lipolytica gene library was constructed in vector YRp7 and transformed into a Saccharomyces cerevisiae strain lacking both major acid phosphatase activities. A 2.18 kb genomic sequence restoring the ability to hydrolyze alpha naphthyl phosphate was isolated. Its sequencing revealed an ORF encoding 358 amino acids without significant homology with any known phosphatase. A putative signal peptide and several possible sites for N-glycosylation were identified. Phosphate-regulated expression of the cloned gene was observed in Y. lipolytica. Disruption data favoured the hypothesis that it might encode a minor phosphatase species. PMID- 1423724 TI - Direct induction of tetraploids or homozygous diploids in the industrial yeast Saccharomyces cerevisiae by hydrostatic pressure. AB - Hydrostatic pressure and a dye plate method were used to investigate the direct induction of tetraploids or homozygous diploids from the industrial diploid or haploid yeast Saccharomyces cerevisiae. Above 200 MPa, hydrostatic pressure greatly inactivated the strains HF399s1 (alpha haploid), P-540 (a/alpha diploid), and P-544 (a/alpha diploid). At the same time, when pressure-treated cells of these strains were spread on a dye plate, some of the visible colonies were stained red/blue or dark blue (variant colonies); the rest stained violet, similar to colonies originating from diploid cells or haploid cells that were not pressure-treated. In addition, above 100 MPa, the formation of variant colonies increased with increasing pressure, and maximized (1 x 10(-1)) at 200 and 250 MPa, respectively. The size of almost all variant cells from P-544, P-540, and HF399s1 was visibly increased compared with that of untreated cells and the measured cellular DNA content of P-540 and HF399s1 was double that of untreated cells. Furthermore, based on random spore analysis and mass-matings, induced variants in the diploid strains were found to be tetraploid with an a/a/alpha/alpha genotype at the mating-type locus or, in the haploid strains, homozygous diploid with an alpha/alpha genotype. From these results we conclude that pressure treatment in combination with a dye plate is a useful method for strain improvement by direct induction of tetraploids or homozygous diploids from industrial strains whether diploid or haploid. PMID- 1423725 TI - Expression of a bacterial aspartase gene in Aspergillus nidulans: an efficient system for selecting multicopy transformants. AB - The Escherichia coli aspartase gene aspA has been expressed in the fungus Aspergillus nidulans using the powerful constitutive gpdA promoter and trpC terminator, both from A. nidulans. Multiple, but not single, copies of aspA overcome nutritional deficiencies resulting from the loss of catabolic NAD-linked glutamate dehydrogenase. They also circumvent certain nutritional deficiencies resulting from loss of the positive-acting regulatory gene product mediating nitrogen metabolite repression. Both of these cases of physiological suppression involve the aspartase-catalyzed catabolism of aspartate to ammonium plus fumarate. No physiological evidence for the opposite reaction leading to aspartate synthesis was obtained as multiple copies of aspA did not affect the phenotype resulting from the loss of anabolic NADP-linked glutamate dehydrogenase. The use of vectors containing aspA and recipients lacking NAD linked glutamate dehydrogenase is an efficient means of selecting multicopy transformants in A. nidulans and also offers the possibility to select strains having increased aspartase levels from original transformants. PMID- 1423727 TI - Transformation of Acremonium coenophialum, a protective fungal symbiont of the grass Festuca arundinacea. AB - Acremonium coenophialum is a mutualistic mycosymbiont and natural agent of biological protection of the widely distributed grass Festuca arundinacea (tall fescue). An electroporative transformation system was developed for A. coenophialum. Segments of DNA 5' to the beta-tubulin gene (tub2) of the closely related ascomycete Epichloe typhina, fused to the Escherichia coli hph gene encoding hygromycin B phosphotransferase, conferred hygromycin resistance when introduced into A. coenophialum by electroporation. The incorporation of the Emericella nidulans trpC terminator greatly increased protoplast germination on selective medium and improved transformation efficiencies 30-200% depending on the plasmid construct. Plasmid pCSN43, which incorporates the trpC controlling elements for hph expression, was also used to transform A. coenophialum. Southern blot analysis of ten pCSN43 transformants indicated the possibility of random integration of this vector into the genome. PMID- 1423726 TI - Genetic organization and structural features of maranhar, a senescence-inducing linear mitochondrial plasmid of Neurospora crassa. AB - The nucleotide sequence of maranhar, a senescence-inducing linear mitochondrial plasmid of Neurospora crassa, was determined. The termini of the 7-kb plasmid are 349-bp inverted repeats (TIRs). Each DNA strand contains a long open reading frame (ORF) which begins within the TIR and extends toward the centre of the plasmid. ORF-1 codes for a single-subunit RNA polymerase that is not closely related to that encoded by another Neurospora plasmid, kalilo. The ORF-2 product may be a B-type DNA polymerase resembling those encoded by terminal protein linked linear genetic elements, including linear mitochondrial plasmids and linear bacteriophages. A separate coding sequence for the terminal protein could not be identified; however, the DNA polymerase of maranhar has an amino-terminal extension with features that are also present in the terminal proteins of linear bacteriophages. The N-terminal extensions of the DNA polymerases of other linear mitochondrial plasmids contain similar features, suggesting that the terminal proteins of linear plasmids may be comprised, at least in part, of these cryptic domains. The terminal protein-DNA bond of maranhar is resistant to mild alkaline hydrolysis, indicating that it might involve a tyrosine or a lysine residue. Although maranhar and the senescence-inducing kalilo plasmid of N. intermedia are structurally similar, and integrate into mitochondrial DNA by a mechanism thus far unique to these two plasmids, they are not closely related to each other and they do not have any nucleotide sequence features, or ORFs, that distinguish them clearly from mitochondrial plasmids which are not associated with senescence and most of which are apparently non-integrative. PMID- 1423728 TI - Genomic organization of a cellulase gene family in Phanerochaete chrysosporium. AB - Southern blot and nucleotide sequence analysis of Phanerochaete chrysosporium BKM F-1767 genomic clones indicate that this wood-degrading fungus contains at least six genes with significant homology to the Trichoderma reesei cellobiohydrolase I gene (cbh1). Using pulsed-field gel electrophoresis to separate P. chrysosporium chromosomes, the six cellulase genes were found to hybridize to at least three different chromosomes, one of which is dimorphic. The organization of these genes was similar in another P. chrysosporium strain, ME 446. It is clear that, unlike T. reesei, the most well-studied cellulolytic fungus, P. chrysosporium contains a complex, cbh1-like gene family. PMID- 1423729 TI - Length heterogeneity in ITS 2 and the methylation status of CCGG and GCGC sites in the rRNA genes of the genus Peronosclerospora. AB - The polymerase chain reaction (PCR) was used with primers complementary to conserved flanking sequences to amplify the internal transcribed spacer 2 (ITS 2) of the rDNA repeat units of five Peronoscleropora isolates, one each of P. sorghi, P. maydis, P. sacchari and two of P. zeae. In contrast to the situation found in most-fungi that have been examined, length heterogeneity was evident in each sample. The rDNA composition of the amplified bands was confirmed by Southern hybridizations using an ITS 2 amplified from P. sorghi and cloned rDNA from Neurospora crassa as probes. Length heterogeneity was also detected in genomic DNA digests using the same probes. In addition to one dominant fragment for each isolate, there were several less frequent fragments of different sizes, and the isolate(s) for each species had a unique banding pattern for ITS 2. The absence of 5-methylcytosine residues in CCGG and GCGC sequences in the ribosomal genes of these four Peronosclerospora species was demonstrated by the production of identical banding patterns with ribosomal DNA probes following digestion of genomic DNA with MspI and HpaII, and by complete digestion with CfoI. PMID- 1423731 TI - The electrophoretic banding pattern of the chromosomes of Pichia stipitis and Candida shehatae. AB - The electrophoretic karyotype of fu1ur strains of P. stipitis and five strains of C. shehatae were compared by means of OFAGE and TAFE techniques. Although the number of chromosomal bands was six in all cases except one, P. stipitis revealed a clearly distinct pattern in comparison to C. shehatae. Both yeasts showed remarkable chromosome length polymorphism. PMID- 1423730 TI - Identification of a chloroplast-encoded secA gene homologue in a chromophytic alga: possible role in chloroplast protein translocation. AB - SecA is one of seven Sec proteins that comprise the prokaryotic protein translocation apparatus. A chloroplast-encoded secA gene has been identified from the unicellular chromophytic alga Pavlova lutherii. The gene predicts a protein that is related to the SecA proteins of Escherichia coli and Bacillus subtilis. The presence of secA, as well as the previously described secY and hsp70 genes, on the chloroplast genome of P. lutherii suggests that this eukaryotic organism utilises protein translocation mechanisms similar to those of bacterial cells. PMID- 1423732 TI - Structure of the Cochliobolus heterostrophus glyceraldehyde-3-phosphate dehydrogenase gene. PMID- 1423733 TI - Circadian rhythm of the endopeptidase 22.19 (EC 3.4.22.19) in the rat brain. AB - The endopeptidase 22.19 (EC 3.4.22.19) has been associated with the metabolism of neuropeptides by its ability to convert small enkephalin-containing peptides (8 to 13 amino acids) into enkephalins. In addition, this enzyme cleaves the Arg8 Arg9 bond of neurotensin and the Phe5-Ser6 bond of bradykinin. We analyzed the circadian variation of endopeptidase 22.19 in the whole and individual areas of the rat brain. Endopeptidase 22.19 activity was analyzed by high-performance liquid chromatography (HPLC) using bradykinin as an operative substrate. Enzymatic specific activities were analyzed by rhythmometric methods and indicate a circadian fluctuation of endopeptidase 22.19 specific activity (mU of enzyme/mg of protein) in the whole brain [p less than 0.001, mesor (M) = 7.62, amplitude (A) = 2.89, and acrophase (phi) = 23:08 h], striatum (p less than 0.001, M = 2.92, A = 0.62, phi = 23:03 h), hypothalamus (p less than 0.001, M = 3.15, A = 0.86, phi = 01:12 h), periaqueductal gray matter (p less than 0.005, M = 2.62, A = 0.34, phi = 22:35 h), and cerebellum (p less than 0.014, M = 4.27, A = 0.88, phi = 17:12 h). The circadian rhythmicity in endopeptidase 22.19 specific activity suggests that light may have an effect on the peptidase activity in whole brain and in areas of the central nervous system and may be essential for the mechanisms of circadian fluctuations of neuropeptides in the brain. PMID- 1423734 TI - Effects of indoleamines and short photoperiods on the encystment of Gonyaulax polyedra. AB - At a temperature of 15 degrees C, Gonyaulax polyedra responds to short days (light less than or equal to 10 h) by transition to the stage of a resting cyst. At 20 degrees C, even an light:dark (LD) cycle of 6:18 is incapable of inducing this process. In otherwise cyst-inducing conditions (15 degrees C; 10 h of light per day), an interruption of the scotophase by 2 h of light (LDLD 8:2:2:12 or 2:2:8:12) prevented encystment. Cyst induction is, therefore, initiated by a photoperiodic mechanism rather than by light deficiency. In Gonyaulax, photoperiodism may be mediated by the action of indoleamines. Melatonin, which exhibits a circadian rhythmicity in this organism, leads to encystment when given 1 h before lights-off in LD 11:13 at 15 degrees C, i.e., under otherwise noninducing conditions. Again, at 20 degrees C, melatonin is inefficient. Some analogues of melatonin, in particular, 5-methoxytryptamine and N,N-dimethyl-5 methoxytryptamine, and, at high concentrations, their respective precursors, serotonin and bufotenin, are capable of inducing cyst formation at 20 degrees C and in LD 12:12, whereas N-acetyl-serotonin does not show this effect. PMID- 1423735 TI - A circadian rhythm in the activity of superoxide dismutase in the photosynthetic alga Gonyaulax polyedra. AB - The activity of superoxide dismutase in cell-free extracts of Gonyaulax made at different times of day and night was found to be three to four times higher during the day. This rhythm continued in cells kept in constant light, indicating that the regulation can be attributed to the cellular circadian clock. PMID- 1423736 TI - Effects of tetraethylammoniumchloride (TEA), vanadate, and alkali ions on the lateral leaflet movement rhythm of Desmodium motorium (Houtt.) Merr. AB - The period (approximately 3-5 min) of the ultradian rhythm of the lateral leaflet movement of Desmodium motorium is strongly lengthened (less than or equal to 30 40%) by the K+ channel blocker tetraethylammoniumchloride (20, 30, and 40 mM) and vanadate (0.5 and 1 mM), which is an effective inhibitor of the plasma membrane bound H+ pump. The alkali ions K+, Na+, Rb+, and Cs+ (10-40 mM) shorten the period only slightly (less than or equal to 10-15%). Li+ (5-30 mM), however, increases the period of the leaflet rhythm drastically (less than or equal to 80%). We concluded that the plasmalemma-H(+)-ATPase-driven K+ transport through K+ channels is an essential component of the ultradian oscillator of Desmodium, as has been proposed for the circadian oscillator. PMID- 1423737 TI - Behavioral and morphological studies of fetal neural transplants into SCN lesioned rats. AB - We have studied the effects of fetal neuronal grafts on the temporal pattern of drinking behavior of suprachiasmatic nuclei (SCN)-lesioned adult rats. Additionally, in an independent set of animals, the immunohistochemical staining for vasopressin, vasoactive intestinal polypeptide, and neuropeptide Y and the retinal connections to the hypothalamus were studied. The behavioral experiments indicate that anterior hypothalamic transplants induced reorganization of the temporal pattern of drinking behavior when placed in the third ventricle of adult hosts bearing complete SCN lesions, but not when placed in a cavity in the occipital cortex. Such rhythmicity persists only when the animals were recorded under constant darkness but not under constant light, indicating that the restored rhythmicity was generated endogenously but that the oscillator was extremely sensitive to light. Fetal occipital cortex induced reorganization of the temporal pattern of previously arrhythmic hosts, but it disappeared when the animals were recorded under constant light or constant darkness. It is clear that this rhythmicity was exogenous. In contrast to the cortical transplants, the hypothalamic transplants showed a morphological organization similar to that found in the normal hypothalamus regardless of their placement in the host brain. From these observations it is concluded that development of neocortex is more affected by environmental factors than that of the hypothalamus. Both hypothalamic and cortical transplants induced sprouting of retinal fibers into the anterior hypothalamus and the grafted tissue. It is possible that such fibers could be the neuroanatomical substrate by which rhythmicity is induced by cortical tissue. PMID- 1423738 TI - Pinealectomy decelerates the circadian food intake rhythm of cervically sympathectomized rabbits. AB - Long-term records of the free-running food intake rhythms were obtained from 26 young adult blinded rabbits that were subjected in the course of recording to bilateral superior cervical ganglionectomy (sympathectomy). This always resulted in acceleration of the rhythm (mean delta tau = -0.35 h). Some 4 months afterwards, 12 rabbits were pinealectomized and after another 4 months sham pinealectomized also. In the other 14 animals, these operations were performed in the reverse order. It appeared that suctioning away part of the ventricular walls during sham pinealectomy was followed by a slight reduction in tau (mean = -0.07 h) that could be largely attributed to the spontaneous gradual reduction of tau that occurred throughout all experiments. On the other hand, total pinealectomy in these already sympathectomized blinded rabbits always resulted in a substantial deceleration of the rhythms (mean delta tau = +0.23 h). These observations on blinded rabbits suggest that a sympathetically denervated pineal gland releases appreciable amounts of melatonin or of another hormone with a melatonin-like accelerating effect on the circadian pacemaker (SCN). PMID- 1423739 TI - Nocturnal headache-hypertension syndrome: a chronobiologic disorder. AB - The study of blood pressure (BP) monitoring in essential hypertensive patients recurrently suffering from nocturnal headache revealed a rhythmic elevation of sphygmomanometric values during the night. Such a finding was not detected in essential hypertensive patients suffering from occasional headache. The nocturnal elevation of BP was seen to be paralleled by the circadian peak of heart rate, suggesting that the disorder is a systemic phenomenon. Importantly, the headache episodes were seen to disappear after antihypertensive therapy that was adjusted to lower the nocturnal increase of BP. The therapeutic results suggested that the nocturnal headache was dependent on the phasic elevation of BP. The beneficial effects further suggested that the nocturnal headache and the nocturnal elevation of BP may represent a particular syndrome with a cause-effect relationship. The term "nocturnal headache-hypertension syndrome" is proposed. PMID- 1423740 TI - Some perturbations that disturb the circadian melatonin rhythm. AB - The circadian melatonin rhythm is highly reproducible and generally not easily altered. The few perturbations that are capable of significantly changing either the amplitude or the pattern of the 24-h melatonin rhythm are summarized herein. Aging alters cyclic melatonin production by decreasing the amplitude of the nocturnal melatonin peak in all species in which it has been studied. The best known acute suppressor of nocturnal melatonin is light exposure. The brightness of light required to acutely depress pineal melatonin production is species dependent; of the visible wavelengths, those in the blue range (approximately 500 520 nm) seem most effective in suppressing melatonin production. Nonvisible, nonionizing radiation in the extremely low frequency range (e.g., 60 Hz) seems also capable of altering pineal melatonin synthesis. Hormones have relatively little influence on the circadian production of melatonin, although either adrenalectomy or hypophysectomy does attenuate the amplitude of the melatonin cycle. Exercise at the time of high melatonin production rapidly depresses pineal concentrations of the indole without influencing its synthesis; the mechanism of this suppression remains unknown. PMID- 1423741 TI - Fluorescence quenching studies on binding fluoreno-9-spiro-oxazolidinedione to human serum albumin. AB - Human serum albumin fluorescence quenching by fluorene-9-spiro-oxazolidinedione has been analyzed as a function of temperature. Such temperature dependence suggests that the mechanism of the quenching process is static in origin. This type of quenching implies that a non-fluorescent complex between oxazolidinedione and serum albumin has been formed and following the Stern-Volmer relationship we have calculated the binding constant. Thermodynamic parameters were also determined. The positive and large values of entropy and the negative value for enthalpy suggest that both hydrophobic and electrostatic interactions may play an important role in the stabilization of the complex. Finally, the irreversible changes in the spectral properties of HSA are interpreted in binding terms. PMID- 1423742 TI - Oat lipids-induced covalent DNA modifications (I-compounds) in female Sprague Dawley rats, as determined by 32P-postlabeling. AB - Previous studies have shown that the presence of oats in the diet contributes to formation of I-compounds (age-dependent covalent DNA modifications detected by 32P-postlabeling assay) in female Sprague-Dawley rat liver DNA. The current study explored the possible ingredients in oats responsible for the observed effects on DNA. Feeding AIN-76A diet containing 5% oat lipids (obtained by methanol extraction and dissolved in trioctanoin) in place of corn oil for 2 months successfully induced the formation of 3 oats-specific (spots 2-4) and 4 natural ingredient diet-specific I-compounds (spots 6-9) in liver DNA. Barley, an oatlike cereal, induced 3 of these spots at very low intensities but not the 3 oats specific I-spots. Oral administration of oat lipids to weanling rats of both sexes for 7 days elicited trace amounts of the oats-specific spots and spot 9 in liver DNA. However, when oat lipids were given at 6 or 9 weeks of age, the oats specific spots were detected at high levels in female but not in male rats. These oats-related DNA modifications were also present in 6-week-old female rats which had received oat lipids p.o. for 2 or 3 days or i.p. for 4 days. Rats given trioctanoin or extracts from natural ingredient Wayne diet (lacking oats) did not show any of these spots. On the other hand, rats treated with extracts from an oats-containing Teklad diet displayed a trace amount of one of these I-compounds. Oat lipids did not induce any extra spots in rat kidney DNA. Feeding of AIN diet supplemented with oats to female Syrian hamsters did not elicit any renal or hepatic DNA alterations, as detected by 32P-postlabeling. Rats fed oat lipids supplemented AIN diet or Purina diet showed the highest levels of I-compounds overall in liver among all dietary groups and these two groups also had significantly higher hepatic DNA synthesis rates. Oat lipids enhanced kidney DNA synthesis also. The total hepatic or renal cytochrome P-450 contents were not significantly affected by different diets. These results demonstrate a novel link between a natural dietary ingredient and covalent DNA modifications and shed light on the origins of certain I-compounds. PMID- 1423744 TI - The involvement of primary and secondary metabolism in the covalent binding of 1,2- and 1,4-dichlorobenzenes. AB - The microsomal oxidation of 1,2-[14C]- and 1,4-[14C]dichlorobenzene (DICB) was investigated with special attention for possible differences in biotransformation that might contribute to the isomer-specific hepatotoxicity. Major metabolites of both isomers were dichlorophenols (2,5-DICP for 1,4-DICB and 2,3- and 3,4-DICP for 1,2-DICB, respectively) and dichlorohydroquinones. The formation of polar dihydrodiols appeared to be a major route for 1,2-DICB but not 1,4-DICB. Both the hepatotoxic 1,2-DICB and the non-hepatotoxic 1,4-DICB were oxidized to metabolites that covalently interacted with protein and only to a small extent with DNA. Protein binding could be inhibited by the addition of the reducing agent ascorbic acid with a concomitant increase in the formation of hydroquinones and catechols, indicating the involvement of reactive benzoquinone metabolites in protein binding. However, in the presence of ascorbic acid, a substantial amount of protein-bound metabolites of 1,2-DICB was still observed, in contrast to 1,4 DICB where binding was nearly completely inhibited. This latter effect was ascribed to the direct formation of reactive benzoquinone metabolites in a single P450-mediated oxidation of para-substituted dichlorophenols (such as 3,4-DICP) in the case of 1,2-DICB. In contrast, the major phenol isomer derived from 1,4-DICB (i.e. 2,5-DICP) is oxidized to its hydroquinone derivative, which needs prior oxidation in order to generate the reactive benzoquinone species. Residual protein binding in the presence of ascorbic acid could also indicate the involvement of reactive arene oxides in the protein binding of 1,2-DICB, but not of 1,4-DICB. However, MO computer calculations did not provide indications for differences in chemical reactivity and/or stability of the various arene oxide/oxepin tautomers that can be formed from either 1,2-DICB or 1,4-DICB. In conclusion, reactive intermediates in the secondary metabolism of 1,2-DICB lead to more covalent binding than those derived from 1,4-DICB, which correlates very well with their reported hepatotoxic potency. PMID- 1423743 TI - Differential toxicity of cocaine and its isomers, (+)-cocaine and (-)-psi cocaine, is associated with stereoselective hydrolysis by hepatic carboxylesterases in cultured rat hepatocytes. AB - Cocaine induces acute lethal cell injury in rat hepatocytes following N-oxidative metabolic activation by cytochrome P450-dependent and flavin-dependent monooxygenases. Beside this oxidative bioactivation pathway, hepatic carboxylesterases may cleave the carboxymethylester or the benzoylester linkage which leads to molecules found to be non-toxic in vivo. To elucidate the structural requirements of the cocaine molecule for its bioactivation and inactivation, the cytotoxic potential of the natural (-)-cocaine relative to two isomeric forms, (+)-cocaine* (the unnatural enantiomer) and (-)-psi-cocaine (the C2 epimer of the unnatural cocaine) were investigated. Primary short-term cultures of rat hepatocytes obtained from phenobarbital (PB)-pretreated rats were exposed to the drugs for up to 24 h. (-)-Cocaine produced marked time- and concentration-dependent release of lactate dehydrogenase (LDH) into the extracellular medium, whereas the other forms were not cytotoxic (0-1 mM). Furthermore, depletion of cellular glutathione (GSH) with diethylmaleate enhanced LDH release in (-)-cocaine-treated cells and caused marginal cytotoxicity in hepatocytes exposed to the other isomers. To investigate the mechanisms that could be responsible for these isomer-specific effects, the time-dependent metabolic degradation was determined both in cultured hepatocytes and in hepatic microsomes in the presence or absence of the serine carboxylesterase inhibitors, phenylmethylsulfonylfluoride (PMSF) or NaF. All three cocaine analogs were enzymatically degraded, but the rates of ester cleavage greatly varied among the stereoisomers. (-)-Cocaine was primarily N-oxidized via SKF-525A-sensitive pathways, whereas (+)-cocaine was predominantly hydrolyzed by PMSF-sensitive carboxylesterases. In contrast, (-)-psi-cocaine, which is very stable in the absence of cells at 37 degrees C and pH 7.4, was subject to extremely fast enzymatic ester cleavage. In conclusion, these results indicate that the isomer specific differential cytotoxicity of (-)-cocaine, (+)-cocaine and (-)-psi cocaine in hepatocytes may be related to stereoselective differences in the rates of hydrolytic inactivation by hepatic carboxylesterases and that the N-oxidative pathway, resulting in hepatocyte injury, may thus be relevant only for (-) cocaine. PMID- 1423746 TI - Carcinoma of the gall bladder--a disastrous diagnosis? PMID- 1423745 TI - Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth. AB - Propolis, a honey bee hive product, is thought to exhibit a broad spectrum of activities including antibiotic, antiviral, anti-inflammatory and tumor growth inhibition; some of the observed biological activities may be due to caffeic acid (cinnamic acid) esters that are present in propolis. In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100. Also, the effect of these agents on the growth of human colon adenocarcinoma, HT-29 cells and activities of ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) was studied. Mutagenicity was induced in Salmonella typhimurium strains TA 98 and TA 100 plus S9 activation using 5 and 10 micrograms DMAB and antimutagenic activities of 0-150 microM MC, 0-60 microM PEC and 0-80 microM PEDMC were determined. The results indicate that MC, PEC and PEDMC were not mutagenic in the Salmonella tester system. DMAB-induced mutagenicity was significantly inhibited with 150 microM MC, 40-60 microM PEC and 40-80 microM PEDMC in both tester systems. Treatment of HT-29 colon adenocarcinoma cells with > 150 microM MC, 30 microM PEC and 20 microM PEDMC significantly inhibited the cell growth and syntheses of RNA, DNA and protein. ODC and PTK activities were also inhibited in HT-29 cells treated with different concentrations of MC, PEC and PEDMC. These results demonstrate that caffeic acid esters which are present in Propolis possess chemopreventive properties when tested in short-term assay systems. PMID- 1423747 TI - Is it possible to distinguish between complete and partial hydatidiform mole histologically? PMID- 1423748 TI - Cytological diagnosis of bronchial malignancies using the fibreoptic bronchoscope. AB - Bronchial brush and wash material were obtained by fibreoptic bronchoscopy in 200 patients suspected of having bronchial carcinoma. Malignancy was diagnosed in 42, giving a diagnostic yield of 21%. Bronchial brush material showed the highest yield. Morphological cell typing was done on cytological material. Technical considerations, diagnostic criteria, diagnostic yield and accuracy are discussed. PMID- 1423749 TI - The epidemiology of infertility 1976-1988. PMID- 1423750 TI - An outbreak of measles in the Southern Province. AB - During an outbreak of measles in the Southern Province in 1990, 69 patients were admitted to the Professorial Paediatric Unit of Teaching Hospital Galle. Of these, 13 patients had received the measles vaccination. The commonest complication seen was bronchopneumonia. There were 3 deaths, 2 due to bronchopneumonia and 1 to encephalitis. PMID- 1423751 TI - An evaluation of the SAT in the diagnosis of typhoid. AB - Salmonella typhi O and H antibody titres were determined by the Standard Agglutination Test (SAT) in 85 patients with bacteriologically proven typhoid, 102 patients with non-typhoidal febrile illnesses (control group 1), and 170 healthy subjects (control group 2). An O antibody titre of 1/120 occurred in 93% of patients with typhoid fever (7% false negatives), and in 17% and 12% control groups 1 and 2 respectively. An H antibody titre of 1/120 was found only in 64% of patients with typhoid (false negatives in 36%). At titres other than 1/120, the proportion of false negatives or false positives increased ie. the sensitivity and specificity decreased. Although the SAT continues to be used in Sri Lanka as the main diagnostic test in typhoid, the sensitivity and specificity of this test fall below the requirements of a useful diagnostic test. PMID- 1423752 TI - Long term survival in subacute sclerosing panencephalitis. AB - A case of subacute sclerosing panencephalitis (SSPE) with a long survival of 8 years is reported. Long term survival in SSPE has not been previously reported from Sri Lanka. PMID- 1423753 TI - Accidental disc battery ingestion. PMID- 1423754 TI - Central retinal artery occlusion associated with migraine. AB - We report a case of central retinal artery occlusion associated with migraine. Although this association is rare, the importance of early diagnosis, and the long-term management of this form of complicated migraine are briefly discussed. PMID- 1423755 TI - Relations between the averaged 13C nuclear magnetic resonance chemical shift and the carcinogenic activity of polycyclic aromatic hydrocarbons. AB - 13C Nuclear magnetic resonance (13C-NMR) spectra were measured for polycyclic aromatic hydrocarbons (PAH) to examine the correlation between their chemical shift and carcinogenicity. We confirmed our previous proposition that the carcinogenicity of PAH molecules can be predicted from the value of the averaged 13C-NMR chemical shift. It was also found, using the averaged chemical shift as a parameter, that several quantum chemical indices for the intermediate states of the metabolic transformation are correlated with the carcinogenic activity of PAH. This indicates that the averaged chemical shift can be applied to investigate the metabolic transformation of carcinogenicity. PMID- 1423756 TI - Indonesian medicinal plants. I. Chemical structures of calotroposides A and B, two new oxypregnane-oligoglycosides from the root of Calotropis gigantea (Asclepiadaceae). AB - Two new oxypregnane-oligoglycosides named calotroposides A (1) and B (2) have been isolated from the root of Calotropis gigantea (Asclepiadaceae), an Indonesian medicinal plant, and their chemical structures have been elucidated by chemical and spectroscopic methods as 12-O-benzoyllineolon 3-O-beta-D cymaropyranosyl(1----4)-beta-D-oleandropyranosyl( 1----4)- beta-D oleandropyranosyl(1----4)-beta-D-cymaropyranosyl(1--- -4)-beta-D- cymaropyranoside and 12-O-benzoyldeacetylmetaplexigenin 3-O-beta-D cymaropyranosyl(1---4)-beta-D-oleandropyranosyl(- ---4)- beta-D oleandropyranosyl(1----4)-beta-D-cymaropyranosyl(1--- -4)- beta-D cymaropyranoside, respectively. PMID- 1423758 TI - Synthesis and antihypertensive activity of 1,4-dihydropyridine derivatives with a 4-(disubstituted phenyl) ring and an aminoalkyl ester group: highly potent and long-lasting calcium antagonists. AB - New 1,4-dihydropyridine derivatives bearing a 4-(disubstituted phenyl) ring and an aminoethyl ester or an amino-2,2-dimethyl-propyl ester were synthesized and their antihypertensive activities were examined in normotensive rats and spontaneously hypertensive rats. The effects of phenyl substituents and ester groups on the antihypertensive activity are discussed. Several compounds showed a more potent antihypertensive activity than nicardipine and most compounds had a longer duration of action. Among them, 7B.HCl (TC-81) showed highly potent and long-lasting activity and was selected as a candidate for further pharmacological investigations. PMID- 1423757 TI - Indonesian medicinal plants. II. Chemical structures of Pongapinones A and B, two new phenylpropanoids from the bark of Pongamia pinnata (Papilionaceae). AB - Two new phenylpropanoids named pongapinone A (1) and pongapinone B (2) were isolated from the bark of Pongamia pinnata (Papilionaceae), an Indonesian medicinal plant, and their chemical structures have been elucidated on the basis of their physicochemical properties. Pongapinone A (1) was found to inhibit interleukin-1 production. PMID- 1423759 TI - Synthesis and antihypertensive activity of 3-acetoxy-2,3-dihydro-5-[2- (dimethylamino)ethyl]-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one (diltiazem) derivatives having substituents at the 8 position. AB - In order to improve the potency and duration of biological actions of diltiazem, a number of 1,5-benzothiazepine derivatives having the substituents at the 8 position were prepared and evaluated for their antihypertensive activity in spontaneously hypertensive rats. The introduction of methyl, ethyl, isopropyl, benzyl, methoxy, ethoxy, phenoxy, and methylthio groups increased the antihypertensive activity and prolonged duration of action, whereas cyclohexyl, cyclopentoxy, tolyloxy, p-methoxyphenoxy and phenylthio derivatives were less active than diltiazem. Among them, the 8-benzyl and phenoxy derivatives showed the most potent and long-lasting antihypertensive action. PMID- 1423760 TI - Analgesic components from bornean medicinal plants, Tabernaemontana pauciflora Blume and Tabernaemontana pandacaqui Poir. AB - The analgesic components were isolated from a Bornean medicinal plant, Tabernaemontana pauciflora Blume (syn. Ervatamia blumeana Mark gr.), and the major components were identified as coronaridine and 3-(2-oxopropyl)coronaridine. Four minor components were estimated to be 5R- and 5S-(2-oxopropyl)coronaridine, 3-(2-oxopropyl)voacangine and 3,3'-(oxopropyl)dicoronaridine, which might be produced during the isolation process. Voacangine was also isolated as a major component of T. pandacaqui Poir. Coronaridine and voacangine exhibited significant analgesic and hypothermic effects in mice at a dose of 25 mg/kg, p.o., while 3-(2-oxopropyl)coronaridine was less effective. The former two compounds also revealed a surface anesthesia. PMID- 1423761 TI - Purgative activity and principals of the fruits of Rosa multiflora and R. wichuraiana. AB - Pseudocarps or seeds of Rosa multiflora, crude drug "Eijitsu" have been used as purgative in Japanese traditional medicine. R. wichuraiana was generally thought to be able to substitute for the plant. The n-butanol fractions of both plant seeds were tested on purgative activities with mice, and the values of the 50% effective dose (ED50) were 5.6 g/kg as the seed weight for R. multiflora and 57 g/kg as the seed weight for R. wichuraiana. From pseudocarps of R. multiflora, a new purgative compound, multinoside A acetate, was isolated, and its ED50 value was tested to be 150 mg/kg (77-291 mg/kg, 95% confidence limit). The other isolated compounds were three known quercetin glycosides, quercetin 3-O-xyloside, isoquercitrin and hyperin. From pseudocarps of R. wichuraiana, three quercetin glycosides, isoquercitrin, hyperin and quercetin 3-O-beta-D-glucuronide were isolated similarly, but no purgative components of R. multiflora were detected. PMID- 1423762 TI - Platelet aggregation inhibitors and inotropic constituents in Pyrolae herba. AB - The chloroform-soluble and n-butyl alcohol-soluble fractions of water extract of Pyrolae Herba inhibited platelet aggregation induced by arachidonic acid and showed a positive inotropic effect. A new naphthoquinone and a new tetralone derivative and known chimaphilin, acetovanillon, and toluhydroquinone were isolated as active constituents. Three new tetralone derivatives were also obtained from an active fraction. The structures of the new compounds were elucidated. PMID- 1423763 TI - Lignified materials as medicinal resources. V. Anti-HIV (human immunodeficiency virus) activity of some synthetic lignins. AB - A class of synthetic lignins (dehydrogenation polymers of p-coumaric acid, ferulic acid, and caffeic acid) inhibited cytopathogenicity of HIV-1 and HIV-2 infection. The ratio of cytotoxic to anti-HIV (human immunodeficiency virus) doses depended strongly on conditions during polymer preparation. The activity increased when polymers were treated with reducing agent NaBH4, whereas it decreased when treated with oxidizing agent ceric ammonium nitrate. The polymers inhibited expression of HIV-specific antigen in the infected cells and also inhibited HIV-binding to the cells, but not completely, even at doses that almost completely inhibited the HIV-induced cytopathogenic effect. These results suggest that lignin structure, regardless of whether synthetic or natural, may inhibit HIV replication by an unidentified process, and thus prove to be a new class of anti-HIV agents possibly effective in the treatment of AIDS (acquired immunodeficiency syndrome). PMID- 1423764 TI - Polysaccharides in fungi. XXX. Antitumor and immunomodulating activities of two polysaccharides from the fruiting bodies of Armillariella tabescens. AB - The effects of two polysaccharides, AT-HW and AT-AL obtained from the fruiting bodies of Armillariella tabescens on murine sarcoma 180 tumor and peritoneal macrophages were examined at intraperitoneal administration. AT-HW from the hot water extract and AT-AL from the alkaline extract significantly inhibited the tumor, and the results of different administration schedule and phagocytic system blockade suggested that the mechanism of AT-AL differed from that of AT-HW and branched (1----3)-beta-D-glucans. AT-HW and AT-AL showed reticuloendothelial system-potentiating activity, increased the number of peritoneal exudate cells, activated on macrophages (acid phosphatase activity, glucose consumption, superoxide anion production), and enhanced mitogenic reaction, although AT-HW did not produce superoxide anion in vitro. PMID- 1423765 TI - Effects of 3,3'-dihydroxy-alpha,beta-diethylstilbene and 3,3',4,5' tetrahydroxystilbene on microtubule assembly in vitro, aneuploidy induction, and cellular microtubule and actin networks. AB - We examined the inhibitory activities of 3,3'-dihydroxy-alpha,beta diethylstilbene (DDS) and 3,3',4,5'-tetrahydroxystilbene (THS) on microtubule assembly in vitro and their effects on chromosome number and cellular microtubule networks in Chinese hamster V79 cells. DDS showed half the inhibitory activity of diethylstilbestrol (DES) on microtubule assembly in vitro, while THS had none of the inhibitory activity. DDS induced tetraploid at 30 microM, whereas THS was found to be inactive. Furthermore, DDS disturbed cellular microtubule networks at 100 microM. We also examined the effects of DES, DDS and THS on cellular actin networks in mouse BALB 3T3 cells. DES induced a change of actin stress fiber distribution and THS had similar activity, while DDS showed no activity. PMID- 1423766 TI - Intravenously administered (1----3)-beta-D-glucan, SSG, obtained from Sclerotinia sclerotiorum IFO 9395 augments murine peritoneal macrophage functions in vivo. AB - Effect of intravenously (i.v.) or intraperitoneally (i.p.) administered (1----3) beta-D-glucan, SSG, obtained from Sclerotinia sclerotiorum IFO 9395 on the murine peritoneal macrophage (PM) functions were examined. A single i.v. administration of SSG increased the number of PMs at a dose of 250 micrograms/mouse, and the peak appeared 4 d after administration. However, no special change was observed on peritoneal exude cell (PEC) populations. These PMs showed augmented lysosomal enzyme activity and the peaks appeared in 2 phases, on days 2 and 10. In contrast, SSG administered i.p. (250 micrograms/mouse) increased the number of PMs and enhanced the lysosomal enzyme activity of PMs from day 4, and a broad peak appeared until days 8--12. The populations of PECs were also changed by i.p. injection of SSG. Additionally, SSG administered i.v. enhanced phagocytic activity, H2O2 production and interleukin 1 (IL-1) production, and the kinetics of the activation differed depending on the activities. These data suggest that the effects of SSG on macrophage functions are different depending on administration routes, and there are some different mechanisms in the activation of macrophages in vivo by SSG. PMID- 1423767 TI - The core structure and immunological activities of glycyrrhizan UA, the main polysaccharide from the root of Glycyrrhiza uralensis. AB - The controlled Smith degradation and limited hydrolysis of glycyrrhizan UA, the main phagocytosis-activating polysaccharide isolated from the root of Glycyrrhiza uralensis FISCHER, was performed. The reticuloendothelial system-potentiating, anti-complementary and alkaline phosphatase-inducing activities of glycyrrhizan UA and its degradation products were investigated. Methylation analyses of primary, secondary and tertiary Smith degradation products and of the limited hydrolysis product indicated that the core structural features of glycyrrhizan UA include a backbone chain composed of beta-1,3-linked D-galactose. All of the galactose units in the backbone carry side chains composed of mainly alpha-1,5 linked L-arabino-beta-1,6- or 1,3-linked D-galactose residues at position 6. Removal of the arabinosyl side chains caused a pronounced decrease in immunological activity. PMID- 1423768 TI - The study on phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis: synthesis of homogeneous substrates, substrate specificity and other properties. AB - The properties of phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis were studied in detail. The enzyme was extremely thermostable in 0.1% bovine serum albumin and retained 73% of its activity at 100 degrees C for 10 min, while it was labile in the absence of albumin. The enzymatic activity was inhibited by HgCl2 or p-chloromercuriphenylsulfonic acid and restored by dithiothreitol. The kinetic parameters (Km and Vmax) of PI-PLC were determined for the mixed micelle of yeast phosphatidylinositol (PI)/Triton X 100 or sodium deoxycholate. Four PIs having different acyl chains: dilauroylphosphatidylinositol (DLPI), dimyristoylphosphatidylinositol (DMPI), dipalmitoylphosphatidylinositol (DPPI) and dioleoylphosphatidylinositol (DOPI) were synthesized from yeast PI through the processes of deacylation and reacylation, identified by infrared (IR) and Fourier transform nuclear magnetic resonance (FT-NMR) spectra, and subjected to the action of PI-PLC. All the synthetic PIs were hydrolyzed by this enzyme, with DLPI and DMPI being the best substrates. PI-PLC did not catalyze the hydrolysis of the phosphatidylnucleosides 5'-phosphatidylcytidine, 5'-phosphatidyluridine, 5'-phosphatidylthymidine, 5' phosphatidyladenosine and 5'-phosphatidyl-2'-deoxyadenosine. PMID- 1423770 TI - Effect of glutathione on lambda deoxyribonucleic acid strand breaks in the reaction system of glutathione-alloxan in the presence of Fe(3+) ethylenediaminetetraacetic acid. AB - Alkaline sucrose density gradient and agarose gel electrophoresis methods were used to observe lambda deoxyribonucleic acid (DNA) strand breaks by the reaction system of reduced glutathione (GSH) with alloxan in the presence of Fe(3+) ethylenediaminetetraacetic acid (EDTA). When DNA was incubated in the reaction system for 10 min, DNA strand breaks were easily induced. The increasing concentrations of GSH up to 1.0 mM in the reaction system in the presence of 1.0 mM alloxan caused DNA strand breaks in a concentration-dependent fashion and GSH beyond 2.0 mM caused in the strand breaks of DNA by which the fragments with multiple ranges of molecular weight were produced. The strand breaks of DNA in the reaction system containing low concentrations of GSH were protected by catalase and hydroxyl radical (HO.) scavengers but superoxide dismutase (SOD) did not, indicating that such breaks were induced by HO.generated from the Fenton reaction. On the other hand, the strand breaks of DNA at high concentrations of GSH were protected by ethanol and desferrioxamine, but not effectively by SOD and HO.scavengers, suggesting the possible participation of some oxidizing species of iron rather than HO.. These results indicate that HO.or oxidizing species of iron generated in the GSH-alloxan system depending on the concentration of GSH attacks DNA to produce strand breaks. PMID- 1423769 TI - Purification and characterization of adenosine diphosphatase from human umbilical vessels. AB - Adenosine diphosphatase (ADPase) activity was solubilized with a non-ionic detergent, Tween 20, from human umbilical vessels and purified to homogeneity by diethylaminoethyl-Sepharose CL-6B, adenosine 5'-monophosphate-Sepharose 4B, and concanavalin A-Sepharose chromatography. The apparent molecular mass was 75 kDa. The purified enzyme hydrolyzed pyrophosphate bonds of nucleoside di- and triphosphates in the presence of calcium ion. It was insensitive to the adenosine triphosphatase (ATPase) inhibitors, oligomycin and ouabain, and sensitive to sodium azide. Therefore, we concluded that the ADPase activity in human umbilical vessels does not derive from ADPase degrading only ADP but from ATP diphosphohydrolase (EC 3.6.1.5). The broad substrate specificity and the sensitivity to various inhibitors and calcium ion are common to ATP diphosphohydrolase from bovine aorta. However, there might exist some structural difference around the active site, because the antiserum raised in rabbit against the bovine aorta enzyme scarcely inhibited the human umbilical enzyme. PMID- 1423771 TI - New application of human tumor clonogenic assay to in vitro evaluation of tumor targeting efficiency of immunoconjugates. AB - This report proposes an efficient in vitro method for the evaluation of drug targeting with monoclonal antibody as a carrier to tumor cells. Monoclonal antibody (35G; IgG2a) selectively binding to alpha-fetoprotein (AFP) from human hepatoma cells (HuH-7) was conjugated with an anticancer drug, vindesine (VDS). Human tumor clonogenic assay (HTCA) with some modifications was applied to estimate the targeting efficiency of a conjugate (VDS-35G) for the first time. In this assay, VDS-35G was cytotoxically active against HuH-7 cells at a lower concentration (0.5 ng/ml) and for a shorter contact time than VDS (50 ng/ml), while 35G and VDS-normal mouse immunoglobulin conjugate (VDS-n-IgG) were not active against the cells. Both VDS-35G and VDS-n-IgG were inactive against HuH-13 cells established from a human hepatocellular carcinoma producing no AFP. In the conventional monolayer culture assay (MCA), VDS-35G showed little effect on HuH-7 cells at the concentration effective in HTCA. The cytotoxic activity of VDS in MCA was similar to that in HTCA but the cytotoxic activity of VDS-35G in MCA was considerably different from that in HTCA. This discrepancy could be explained by the hypothesis that VDS-35G was directed at stem cells of the HuH-7 cell population sensitively and selectively. HTCA was shown to be a useful in vitro evaluation method for drug targeting. PMID- 1423772 TI - Enhancement of bioavailability of dopamine via nasal route in beagle dogs. AB - Dopamine (DA), which is ineffective by oral administration due to first pass metabolism and is usually injected, was administered to dogs via rectal, dermal, buccal and nasal routes. The nasal route had the highest bioavailability and best avoided first pass metabolism. The effects of the addition of hydroxypropyl cellulose (HPC), sodium deoxycholate, POE (6) hydrogenated caster oil (HCO-60) and Azone on the nasal absorption increased bioavailability from 11.7% (control) to about 20%, 35%, 25% and 68%, respectively. Further, with a combination of 2% HPC and 5% Azone, bioavailability was increased to almost the same level as with i.v. administration. At the same time, plasma concentrations were maintained at a high level for more than 7 h. The increase in bioavailability is presumed to be caused by an enhancement in absorption and prolongation of the time DA is retained in the nasal cavity due to Azone and HPC, respectively. PMID- 1423773 TI - Computer simulation of agglomeration in the Wurster process. AB - A simplified model for computer simulation of agglomeration in the Wurster coating process was constructed using droplet size distribution and the relation between the size of agglomerates and the number of primary particles composing them experimentally determined. Computer simulations were applied to the cases where a 2.5% aqueous solution of hydroxypropyl cellulose (containing sodium carboxymethyl cellulose of 10% on a dry basis) was sprayed on four kinds of sharply fractionized lactose powders between 32 and 75 microns. With cores larger than 53 microns, the agitation exerted on particles strongly suppressed the growth of agglomerates, but the fraction of produced agglomerates reached about 50%. The smallest droplet size that was contributable to agglomeration (critical droplet size) was estimated to be 37.1-49.0 microns, increasing with core size, and the weight fraction of droplets larger than this critical size was only 0.5 2.7%, decreasing with increase in core size. The production of even such a minor amount of coarse droplets could be responsible for significant agglomeration. PMID- 1423774 TI - A novel prodrug of salicylic acid, salicylic acid-glutamic acid conjugate utilizing hydrolysis in rabbit intestinal microorganisms. AB - The fate of salicylic acid-glutamic acid conjugate (salicyl-glutamic acid) following oral, intravenous, intracecal and rectal administration (60, 10, 5 and 5 mg/kg, respectively: salicylic acid equivalent) was examined in rabbits. Salicylic acid was detected in the blood 2 h after oral administration of salicyl glutamic acid and it reached the maximum level (69.4 micrograms/ml) at 18 h after the dose. A high blood concentration of salicylic acid (24.8 micrograms/ml) was observed up to 36 h. But only a small amount of salicyl-glutamic acid was detected in the blood (less than 2.5 micrograms/ml, as salicylic acid). In contrast, unchanged salicyl-glutamic acid was found mainly in the blood following intravenous administration of salicyl-glutamic acid, suggesting that presystemic de-conjugation of salicyl-glutamic acid predominantly occurred. The intestinal mucosal de-conjugation of salicyl-glutamic acid was negligible in the in situ intestinal sac preparation with complete mesenteric venous blood collection. Immediate and very extensive salicylic acid formation in the cecum was found following intracecal administration of salicyl-glutamic acid. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg), a significant inhibition of salicylic acid formation following intracecal administration of salicyl-glutamic acid was observed, indicating that the intestinal microorganisms were responsible for the biotransformation of salicyl-glutamic acid. Also, in vitro incubation of salicyl-glutamic acid with gut contents showed that the primary location of hydrolysis was the hind gut. PMID- 1423775 TI - Esterase-like activity of human serum albumin. VIII. Reaction with amino acid p nitrophenyl esters. AB - The reactions of human serum albumin (HSA) with optically active amino acid p nitrophenyl esters (substrate, S) were examined kinetically at 25 degrees C. The rate data were analyzed in terms of a mechanism involving 1:1 complexing (S.HSA) between S and HSA. The dissociation constant (Ks in M) and the catalytic rate constant (k2 in s-1) of S.HSA were determined. Among ten substrates examined, the reactions with N-carbobenzoxy-D(L)-alanine p-nitrophenyl esters (N-CBZ-D(L) AlaNP) were most accelerated by HSA. Results of the reaction in the presence of excess N-CBZ-D(L)-AlaNP over HSA indicated the existence of one strong reactive site on HSA. The effects of the reversible binding of the site-specific drug and the chemical modification by site-specific reagents on the HSA activity showed that the reactive site towards N-CBZ-D(L)-AlaNP is the R site located near tyrosine-411 residue of HSA. PMID- 1423776 TI - In vitro percutaneous absorption of thiamine disulfide through rat skin from a mixture of propylene glycol and fatty acid or its analog. AB - Percutaneous absorption of thiamine disulfide, (TDS), a lipophilic derivative of thiamine, from a mixture of propylene glycol (PG) and fatty acid (FA) or its analog through rat skin was tested in vitro. Lauric acid (12:0) enhanced the absorption depending on its concentration in PG and showed a maximal enhancement at 10% w/w. At 10% w/v, lauryl alcohol also enhanced the absorption, but less than 12:0, which lauric acid methyl ester suppressed the absorption. The flux of TDS did not depend on the solubility of TDS in the vehicle, but on the permeability coefficient. From these results, it is suggested that FA increases the permeability coefficient not only because FA increases TDS diffusion by disrupting lipid packing in the stratum corneum but also, FA increases TDS partition to lipid phase by interacting with TDS. PMID- 1423777 TI - Effect of methotrexate treatment on the onset of autoimmune kidney disease in lupus mice. AB - In the present study, we examined the effects of methotrexate (MTX) on the development of autoimmune kidney disease in three kinds of autoimmune prone mice, NZB/NZW F1 (BWF1) mice, MRL/Mp-lpr/lpr (MRL/lpr) mice and NZW/BXSB F1 (WBF1) mice. The results showed that MTX delayed the appearance of proteinuria and prolonged survival of both BWF1 and MRL/lpr mice and inhibited the elevation of blood urea nitrogen (BUN) levels which accompanies the development of lupus nephritis. However, MTX treatment did not affect these in WBF1 mice. Furthermore, MTX could not suppress immunoglobulin G (IgG) class anti-deoxyribonucleic acid (DNA) and anti-trinitrophenol (TNP) antibody production in any variety of mice. These suggest that the therapeutic effect of MTX on BWF1 and MRL/lpr mice does not result in the suppression of IgG autoantibody production. PMID- 1423778 TI - Sensitivity to antitumor drugs and vinblastine binding to membrane in rat ascites hepatoma AH66 cells. AB - Rat ascites hepatoma AH66 cells have lower sensitivity to Vinca alkaloids and anthracycline antibiotics than AH66F cells, a subline of AH66 cells. AH66 cells expressed P-glycoprotein, while the protein was not detectable in AH66F cells. There are two affinity sites for [3H]vinblastine binding in the AH66 cell membrane, while AH66F cells have only one affinity site. The high affinity [3H]vinblastine binding in AH66 cells was inhibited by Adriamycin, verapamil, nicardipine, and reserpine. The high affinity site of the binding may be the multidrug transporter, P-glycoprotein. [3H]Vinblastine binding was not influenced by adenosine 3'-5'-monophosphate (AMP), adenosine triphosphate (ATP), or guanosine triphosphate (GTP). The multidrug resistance in AH66 cells may depend on P-glycoprotein which is not modulated by nucleotide. PMID- 1423779 TI - Platelet aggregation inhibitors from Populus sieboldii Miquel. AB - The water extract of Populus sieboldii Miquel (Salicaceae) inhibited arachidonic acid-induced platelet aggregation. Pyrocatechol and salicyl alcohol were isolated as active constituents. Pyrocatechol showed an inhibitory effect on platelet aggregation induced by arachidonic acid with IC100 value of 4 microM, which was 25 times more potent than aspirin. PMID- 1423780 TI - Determination of ornithine conjugates of some carboxylic acids in birds by high performance liquid chromatography. AB - A high-performance liquid chromatographic (HPLC) method for the determination of ornithine conjugation of some carboxylic acids in vitro has been developed. The ornithine conjugates of benzoic acid, p-nitrobenzoic acid, furancarboxylic acid and phenylacetic acid in an incubation mixture with kidney mitochondria were well separated on a reversed-phase C18 column using a mixture of 10 mM ammonium acetate buffer and methanol as the mobile phase. In addition, by varying the pH of the mobile phase and utilizing the absorption wavelengths (nm) of the conjugates it was possible to resolve and specifically detect each conjugate. The calibration curves were linear in the range of 0.2-16 micrograms/ml for all compounds and the detection limits were about 50 ng/ml except for the ornithine conjugate of phenyl acetic acid (S/N = 2). The ornithine conjugation of some carboxylic acids with chicken kidney mitochondria were determined by this assay method. The activity of ornithine conjugation of benzoic acid, furancarboxylic acid, p-nitrobenzoic acid and phenylacetic acid were 14.5, 5.5, 0.5 and 6.9 nmol/mg of protein, respectively. Moreover, the ornithine conjugation and the glycine conjugation of benzoic acid were examined in birds and rodents. The ornithine conjugation was observed only in chicken (14.5 nmol/mg of protein) and mallard (0.99 nmol/mg of protein). PMID- 1423781 TI - Enzyme immunoassay of thyrotropin releasing hormone (TRH). AB - A sensitive and specific double-antibody enzyme immunoassay (EIA) for a thyrotropin releasing hormone (TRH)-like immunoreactive substance has been developed. In order to synthesize TRH-labeled beta-D-galactosidase (beta-gal), a newly devised TRH derivative, pGlu-His-Pro-NH-(CH2)6-NH2 (TRH-Hex), was employed. TRH-Hex was linked to beta-gal by the N-(epsilon-maleimidocaproyloxy) succinimide coupling procedure. For competitive reactions, the TRH antibody was incubated with standard TRH and TRH-Hex-beta-gal (delayed addition). Free and antibody bound enzyme hapten were separated by using an anti-rabbit immunoglobulin G coated immunoplate. Activity of the enzyme on the plate was fluorometrically determined. The present immunoassay allows detection of 0.8 to 100 pmol/well of TRH. PMID- 1423782 TI - Determination of 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine in rat plasma by high-performance liquid chromatography with precolumn fluorescence derivatization. AB - A high-performance liquid chromatographic method with precolumn fluorescence derivatization using 2-(5-chlorocarbonyl-2-oxazolyl)-5,6-methylenedioxybenzofu ran is described for the quantification of 2',3'-dideoxyinosine, a therapeutic drug for acquired immunodeficiency syndrome, and 2',3'-dideoxyadenosine, an anti human-immunodeficiency-viral agent, in rat plasma. The dideoxyribonucleosides and 3'-deoxythymidine (internal standard) in rat plasma (0.1 ml) are cleaned up by a solid-phase extraction technique using an octadecyl silica (ODS) cartridge, Toyopak ODS M, and the dideoxyribonucleosides in the eluate are reacted with the reagent to produce the corresponding fluorescent esters. The esters are separated by chromatography on a reversed phase column, TSKgel ODS-80TM. The detection limits (signal-to-noise ratio = 3) for the dideoxyribonucleosides are 1.3-5.4 pmol on column. Plasma concentrations of 2',3'-dideoxyinosine after intra-jugular venous administration to rat can be monitored by this method. PMID- 1423783 TI - Studies on thermophile products. IV. Structural elucidation of cytotoxic substance, BS-1, derived from Bacillus stearothermophilus. AB - A new cytotoxic substance designated as BS-1 was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563. On the basis of spectral data, the structure of BS-1 was determined as bis(2-hydroxyethyl) trisulfide and confirmed by direct comparison with the synthetic compound. BS-1 exhibited potent cytotoxicity against leukemia P388-D1, leukemia P388, mastocytoma P815, lymphoma EL4 and lymphoma MOLT4. PMID- 1423784 TI - Polysaccharides in fungi. XXIX. Structural features of two antitumor polysaccharides from the fruiting bodies of Armillariella tabescens. AB - An antitumor polysaccharide containing peptide moieties AT-HW ([alpha]D + 31 degrees in water) and an antitumor polysaccharide AT-AL ([alpha]D + 209 degrees in 1 M sodium hydroxide) were isolated from hot-water extract and the alkaline extract of the fruiting bodies of Armillariella tabescens, respectively. Chemical structures of AT-HW and AT-AL were investigated by a combination of chemical and spectroscopic methods. The results indicate that the major constituent of AT-HW (molecular weight, 105000), a heteroglycan, is composed primarily of beta-(1--- 6)-linked D-glucopyranosyl and D-galactopyranosyl residues, and contains their branched residues and terminal sugar (gluco-, manno-, and fucopyranose) residues, in addition to beta-(1----3)-linked D-glucopyranosyl residues, while AT-AL (molecular weight, 93000) is chiefly composed of alpha-(1----3)-linked D glucopyranosyl residues. PMID- 1423785 TI - Physicochemical characteristics and antitumor activities of a highly branched fungal (1----3)-beta-D-glucan, OL-2, isolated from Omphalia lapidescens. AB - Physicochemical properties and antitumor activities of a fungal (1----3)-beta-D glucan, OL-2, isolated from Leiwan (Omphalia lapidescens) were examined. OL-2 showed sharp signals on carbon-13 nuclear magnetic resonance spectrum in dimethylsulfoxide-d6 as a solvent, and these signals were significantly reduced by the addition of distilled water to the concentration of 20%. This phenomenon is consistent with the general property of the gel forming (1----3)-beta-D glucan. Binding of OL-2 to Congo red induced a significant change of lambda max to a longer wavelength, and the concentration to induce gel to sol transition was about 0.7 N; in contrast, the concentration was about 0.2 N in the cases of SPG and curdlan. These observations suggested that the gel structure would be significantly stabilized in the case of OL-2. OL-2 showed no or low antitumor activity against the solid form of Sarcoma 180 by intraperitoneal and intralesional administrations; however, it was effective on the ascites form of Sarcoma 180. Of interest, OL-2 also showed significant antitumor activity against the ascites form of MH-134 when administered with 5-fluorouracil. These results indicated that OL-2 showed characteristic features regarding its physicochemical properties and antitumor activity. PMID- 1423786 TI - Constituents of the seed of Malva verticillata. VIII. Smith degradation of MVS VI, the major acidic polysaccharide, and anti-complementary activity of products. AB - The controlled Smith degradation of MVS-VI, the major acidic polysaccharide having remarkable anti-complementary activity isolated from the seeds of Malva verticillata L., was performed. Methylation analysis of both the primary and the secondary Smith degradation products indicated that the core structural features of MVS-VI include a backbone chain composed of beta-1,3-linked D-galactose residues. The majority of galactose units in the backbone carry side chains composed of beta-1,3- and beta-1,6-linked D-galactosyl residues at position 6. The controlled Smith degradation products showed considerable anti-complementary activity. PMID- 1423787 TI - Influence of melatonin on reproductive behavior in male rats. AB - The influence of melatonin on reproductive behavior was examined by administering it to pinealectomized male rats for 30 consecutive days. After the 30-d administration of melatonin or vehicle, each male rat was introduced into a female rat's cage on the day of proestrus and allowed to mate overnight. All rats administered the vehicle and the pinealectomized rats copulated; five of the twelve melatonin (8.0 mg/kg)-treated rats did not copulate. These findings suggest that melatonin inhibits the reproductive behavior of male rats. PMID- 1423788 TI - Antitumor effect of pluronic F-127 gel containing mitomycin C on sarcoma-180 ascites tumor in mice. AB - Pluronic F-127 (PLF-127) gels were evaluated as a sustained-release vehicle for intraperitoneal administration of mitomycin C (MMC) in order to enhance the therapeutic effects of MMC against a Sarcoma-180 ascites tumor in mice. Tumor cell injections were made on day 0 and injections of MMC in 25% (w/w) PLF-127 on day 1, both intraperitoneally. A prolongation of the life span of tumor-bearing mice following injection of therapeutic PLF-127 was noted, and PLF-127 containing MMC was therapeutically more active than free drug. The high chemotherapeutic efficiency of MMC in PLF-127 was striking at high doses, which would be toxic in the case of the drug alone. PLF-127 gels exhibit reverse thermal behavior and are fluid at refrigerator temperature, but are soft gels at body temperature. The in vitro release experiments indicated that Pluronic gel might serve as a rate controlling barrier and be useful as a vehicle for sustained-release preparations of MMC to be administered intraperitoneally. These results suggest that sustained release occurs in the peritoneum and that effective drug concentrations can be maintained by the preparation. PMID- 1423789 TI - New method of detecting nitric oxide production. AB - Nitric oxide (NO) reacts with H2O2 to produce a rise in potent luminol-dependent chemiluminescence under neutral pH conditions. We applied this reaction to the continuous detection of NO released from the rat isolated perfused kidney with simultaneous pressure changes. Acetylcholine increased NO release dose dependently with the pressure reduction. An NO synthesis inhibitor, NG-monomethyl L-arginine, abolished the release. This inhibition was reversed by the addition of L-arginine. PMID- 1423791 TI - 6-Gingesulfonic acid, a new anti-ulcer principle, and gingerglycolipids A, B, and C, three new monoacyldigalactosylglycerols, from zingiberis rhizoma originating in Taiwan. AB - By monitoring the effects on HCl/ethanol-induced gastric lesions in rats, a new antiulcer principle named 6-gingesulfonic acid was isolated from Zingiberis Rhizoma, the dried rhizome of Zingiber officinale Roscoe (cultivated and processed in Taiwan) together with three new monoacyldigalactosylglycerols named gingerglycolipids A, B and C. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. 6-Gingesulfonic acid showed more potent anti-ulcer activity than 6-gingerol and 6-shogaol. PMID- 1423790 TI - 3-anilino-L-alanine, structural determination of UV-5, a contaminant in EMS associated L-tryptophan samples. AB - An aniline derivative which corresponds to UV-5 in the preceding paper was isolated from the case L-tryptophan sample associated with eosinophilia-myalgia syndrome (EMS). By spectroscopic analyses, the structure was identified as 3 anilinoalanine. The compound was optically active, and the stereochemistry of alanine moiety was determined as L, by comparing the specific rotation with a synthesized 3-anilino-L-alanine. PMID- 1423792 TI - Rapid increase of inositol 1,4,5-trisphosphate content in isolated rat adipose tissue by vanadate. PMID- 1423793 TI - Relation between monocytes in peripheral blood and development of atherosclerosis in hypercholesterolemic rabbits. AB - The relation among circulating monocytes, serum cholesterol and LDL cholesterol in manifestation of atherosclerosis was investigated in hypercholesterolemic rabbits. Serum cholesterol increased sharply and reached a plateau at 12 weeks after the start of cholesterol diet feeding; LDL cholesterol gradually increased until 24 weeks, and the number of monocytes in blood started to decrease abruptly around 12 weeks and resulted in less than 1% total white blood cells at 24 weeks, as reflected by a severe progression of atheroma formation. This result indicated that the decrement of monocyte number in blood was predictive of the presence of severe atherosclerotic plaques. PMID- 1423794 TI - Galloyl-oxypaeoniflorin, suffruticosides A, B, C, and D, five new antioxidative glycosides, and suffruticoside E, A paeonol glycoside, from Chinese moutan cortex. AB - Five new antioxidative glycosides named galloyl-oxypaeoniflorin, suffruticosides A, B, C, and D, and a new paeonol glycoside named suffruticoside E have been isolated from Chinese Moutan Cortex, the root cortex of Paeonia suffruticosa ANDREWS, together with antioxidative galloyl-paeoniflorin. Their structures were elucidated on the basis of chemical and physicochemical evidences. Galloyl oxypaeoniflorin, galloyl-paeoniflorin, suffruticosides A, B, C, and D showed more potent radical scavenging and antioxidative effects than alpha-tocopherol. PMID- 1423796 TI - [Clinical study of the biliary tract pressure in post-operative cholelithiasis]. PMID- 1423795 TI - Kynostatin (KNI)-227 and -272, highly potent anti-HIV agents: conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine. AB - Selective and potent HIV protease inhibitors containing allophenylnorstatine [Apns; (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition-state mimic were designed and synthesized. Among them, conformationally constrained tripeptide derivatives, kynostatin (KNI)-227 and -272 (Fig. 1), exhibited highly potent antiviral activities against a wide spectrum of HIV isolates. Ready availability due to the simple synthetic procedure and the excellent antiviral properties indicate that KNI-227 and KNI-272 are promising candidates as selective anti-AIDS drugs. PMID- 1423798 TI - [Nursing care of plasma exchange/lymphoplasmapheresis in patients with systemic lupus erythematosis]. PMID- 1423797 TI - [Enhancement of administrative management to raise the hospital nursing quality]. PMID- 1423799 TI - [Development of hospices and hospice care]. PMID- 1423800 TI - The role of the ganglioside lipid moiety in the process of ganglioside-cell interactions. AB - The role of the ceramide moiety of gangliosides, together with the deriving aggregative properties of ganglioside in solution, in the process of ganglioside cell interactions was studied. The natural GM1(stearoyl) and the synthetic GM1(acetyl), containing the stearoyl and acetyl groups as the acyl moiety, respectively, were used in binding experiments to rat cerebellar granule cells. Regardless of the cell culture conditions, such as the presence of absence of fetal calf serum, the association of GM1(acetyl) to the cells was much greater than that of GM1(stearoyl). GM1(acetyl) was present in the incubation medium as monomers. After incubation, a large part of the total GM1(acetyl) associated to cells, 76-93% depending on the experimental conditions, was removed by washing with protein solutions. The remaining associated ganglioside was not removed by repeating washing with protein solutions or trypsin treatments and was considered as a component of the membrane. The cell association of GM1(stearoyl), present in solution as monomers as well as micelles, could be classified as serum-labile, trypsin-labile and trypsin-stable. The trypsin-stable form of association, corresponding to the molecules stably inserted into the membrane, was proportionally higher, the proportions varying with increasing incubation time and decreasing ganglioside concentration. This form of association was particularly high when incubation was performed in the presence of fetal calf serum. Incubation experiments performed with a mixture of GM1(stearoyl) and GM1(acetyl) in a molar ratio which allowed their presence in the medium as monomers as well as mixed micelles, led to a ganglioside association suggesting that besides the aggregative properties of the molecule other ganglioside properties are involved in the ganglioside-cell interaction process. PMID- 1423802 TI - Conformations of dibucaine and tetracaine in small unilamellar phosphatidylcholine vesicles as studied by nuclear Overhauser effects in 1H nuclear magnetic resonance spectroscopy. AB - Conformations of dibucaine and tetracaine in small unilamellar phosphatidylcholine vesicles have been investigated by nuclear Overhauser effects (NOEs) in 1H nuclear magnetic resonance spectroscopy. Two-dimensional NOE and chemical exchange correlated spectroscopy (NOESY) and rotating frame NOE spectroscopy (ROESY) methods have been applied for obtaining the NOEs. In the NOESY spectra, NOEs between protons within the drug were overwhelmed by spin diffusion even at a short mixing time. This observation reduced the usefulness of the NOESY method on the one hand, however, on the other hand it facilitated remarkably in revealing signals due to the drug, hidden in the broad resonances of the membranes. In the ROESY spectra, the spin diffusion phenomena were less effective; accordingly the conformations of the drugs interacting with membranes were determined by the ROESY method. The observed NOE data showed that dibucaine takes more than two conformations and that both dibucaine and tetracaine are present as a dimer in the membranes. Molecular dynamics calculations supported these findings. PMID- 1423801 TI - Activation energy and entropy for intramolecular excimer formation in a dipyrenylphosphatidylcholine probe in lamellar and hexagonal lipid phases. AB - Intramolecular excimer formation in pyrene-labeled phosphatidylcholine was used as a tool to determine thermodynamic characteristics of the lamellar to hexagonal phase transitions in a binary lipid system dilinoleoylphosphatidylethanolamine (DLPE)/palmitoyloleoylphosphatidylcholine (POPC). Upon an L alpha/HII phase transition, the activation energy Ea for excimer formation increased from 5.6 +/- 0.2 kcal/mol to 6.3 +/- 0.2 kcal/mol, while the activation entropy delta S decreased from -40.0 +/- 0.8 cal/K.mol to -38.4 +/- 0.8 cal/K.mol. The results are consistent with the idea of molecular splaying of the acyl chains in the hexagonal phase. It is estimated that the molecular area at the terminal carbon of the lipid acyl chains increases by a factor of 2.2 upon the L alpha HII transition in DLPE/POPC. PMID- 1423803 TI - Inhibitors of sterol synthesis. Chemical synthesis of 7 alpha-ethyl and 16 alpha ethyl derivatives of delta 8(14)-15-oxygenated sterols and their effects on 3 hydroxy-3-methylglutaryl coenzyme A reductase in CHO-K1 cells. AB - The enolate of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (II), formed upon treatment of II with potassium tert-butoxide in tert-butanol, was alkylated with ethyl iodide. In addition to the major products, 3 beta-hydroxy-14 alpha-ethyl-5 alpha-cholest-7-en-15-one and its 3 beta-ethyl ether, small amounts of 3 beta hydroxy-7 alpha-ethyl-5 alpha-cholest-8(14)-en-15-one (V), 3 beta-hydroxy-16 alpha-ethyl-5 alpha-cholest-8(14)-en-15-one (VI) and the 3 beta-ethyl ether of VI were isolated. When the enolate of II was formed by treatment with lithium diisopropylamide in tetrahydrofuran, the same alkylation furnished VI as the major product. Reduction of VI with lithium aluminum hydride gave 16 alpha-ethyl 5 alpha-cholest-8(14)-ene-3 beta, 15 alpha-diol (IX) and its 15 beta epimer X, which were separated by column chromatography. Full 1H and 13C nuclear magnetic resonance (NMR) assignments, augmented by nuclear Overhauser effect difference spectra for VI, established the stereochemistry of these diols at C-15 and C-16. The NMR results indicate that the 16 alpha-ethyl group affects the side-chain conformation. The effects of II, V, VI, IX and X on the levels of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase activity were studied in CHO-K1 cells. With the exception of IX, each of the compounds reduced the levels of HMG CoA reductase activity. The order of potency with respect to suppression of the elevated levels of HMG-CoA reductase activity induced by transfer of the cells to lipid-deficient medium, was II greater than V greater than VI greater than X. PMID- 1423804 TI - Methylation effects on the microdomain structures of phosphatidylethanolamine monolayers. AB - Increasing methylation of the headgroup in DPPE results in an increase of minimum area per molecule in highly compressed monolayers at the air-water interface. The shape of solid domains, as observed by epifluorescence microscopy, also exhibits marked changes upon increasing headgroup methylation. Branching domains are observed in DPPE and DP(Me)PE, whereas U-shaped or round domains are observed in DP(Me)2PE and DPPC under our experimental conditions. The domain shape is determined more by the headgroup methylatin than by the corresponding shift in critical temperatures, as shown by the study of PCs of different acyl chain moieties. In mixed lipid monolayers, PC (phosphatidylcholine) and PE (phosphatidylethanolamine) do not mix ideally, as indicated by the non-linear variation of the average area per molecule with composition, and by distinct domain shapes in LE/LC (liquid expanded/liquid condensed) coexisting phases representing PE-enriched or PC-enriched domains in those mixed monolayers. PMID- 1423805 TI - The influence of the molar ratio of cholesteryl hemisuccinate/dipalmitoylphosphatidylcholine on 'liposome' formation after lipid film hydration. AB - The morphology of the structures formed after hydration of lipid films of cholesteryl hemisuccinate/dipalmitoylphosphatidylcholine (CHEMS/DPPC) was investigated in low ionic strength solutions. The importance of addition of a charge inducing agent/geometrical structure such as CHEMS for the formation of stable vesicle dispersions upon hydration was demonstrated. The encapsulated volume measured for CHEMS/DPPC ratios below 1:50 was low. For a ratio of CHEMS/DPPC of 1:30 EM micrographs showed mainly small unilamellar vesicles, with particle sizes between 0.07 and 0.3 microns, together with a small number of much larger vesicles. For ratios of CHEMS/DPPC above 0.1 only unilamellar vesicles and no bilayer stacks were found. The results confirm the hypothesis by Hauser (Biochim. Biophys. Acta 772 (1984) 37-50), that the structures formed upon hydration of charged phospholipid films are unilamellar vesicles, while for neutral phospholipid films upon hydration bilayer stacks and multilamellar vesicles are formed. The effect of CHEMS on the liposome bilayer structure can be mainly ascribed to its charge inducing properties and presumably to a minor extent to its molecular geometry, or to a combination of both. PMID- 1423806 TI - The effect of aging on the physical stability of liposome dispersions. AB - In this study, the effect of aging, in terms of hydrolytic decomposition of the bilayer forming (phospho)lipids, on the physical stability of aqueous liposome dispersion was investigated in partially hydrogenated egg phosphatidylcholine (PHEPC) and egg phosphatidylglycerol (EPG) containing liposomes with or without cholesterol. The physical stability of the liposome dispersions was assessed by measuring the leak-in rate of a non-bilayer interacting hydrophilic marker molecule, calcein and changes in the particle size and its distribution in time. Additionally, permeability of either partially hydrolysed phospholipids or exogenous lyso-phosphatidylcholine(LPC) containing bilayers was calculated. The experiments were performed at 40 degrees C. Liposome dispersions were aged artificially by storing at 60 degrees C. The size of the liposomes and polydispersity index of the dispersions, in general, did not change significantly. The leak-in rate of calcein in externally added LPC containing liposomes was increased relative to the incorporated LPC concentration. The higher the LPC content of the bilayers, the higher the leak-in rate of calcein into liposomes. The leak-in rate of calcein, however, decreased first in partially hydrolysed phospholipids containing liposomes up to around 10% of hydrolysis and, afterwards, it started to increase. The leak-in rate was always lower in partially hydrolysed phospholipids containing liposomes than externally added LPC containing ones. Furthermore, the permeability of cholesterol containing bilayers was also always lower than the bilayers without cholesterol. In conclusion, addition of LPC into liposomal bilayers increases the permeability of bilayer. However, bilayers containing the hydrolysis products of phospholipids, both lyso-phospholipids and free fatty acids, did not show any enhanced permeability up to around 15% hydrolysis. Bilayer permeability is enhanced above 15% hydrolysis. PMID- 1423807 TI - Interaction of antioxidants with depth-dependent fluorescence quenchers and energy transfer probes in lipid bilayers. AB - Three fluorescent, lipophilic, heterocyclic antioxidants were incorporated into lipid bilayers and exposed to depth-dependent nitroxyl fatty acid quenchers. The Stern-Volmer plots curved upward at low quencher concentrations. Quantitative analysis of the results showed that this behavior is consistent with complex formation between quencher and fluorescent antioxidant, where the complex is 2-3 times more fluorescent than the parent fluorophore. At higher quencher concentrations, both free antioxidant and 'bright complex' are quenched dynamically, albeit quenching of the latter is less efficient. The complex probably results from ionic, hydrogen bond and pi-pi interactions. Formation of such a 'bright complex' is also observable in a homogeneous solution of the reactants in cyclohexane. Additional evidence for the complexation of these antioxidants with fatty acids in lipid bilayers is provided by the fact that energy transfer from the antioxidants to anthroyloxy fatty acids occurs at surface concentrations where radiative energy transfer between free molecules should be not be efficient. For directly probing the relative depths of these fluorophores in lipid bilayers we used the aqueous quenchers acrylamide and iodide. They showed that in terms of increasing depth in the bilayer, the order was U-78, 517f < U-78,518e < U-75,412e. Our results, in toto, demonstrate that the Lazaroid antioxidants are incorporated into the lipid bilayer where they occupy strictly defined positions and orientations. Complexation with fatty acyl chains should be mechanistically relevant, since it may enhance antioxidant activity by hindering free radical chain propagation. PMID- 1423809 TI - Growth rate of myelin figures for phosphatidylcholine and phosphatidylethanolamine. AB - The growth length of myelin figures (or myelin tubes) was measured for several kinds of phospholipids using optical microscopy. The measurements were done for myelin figures with various thickness of tube wall. In spite of remarkable differences in morphology between the myelin figures of phosphatidylcholine and those of phosphatidylethanolamine, the growth rates for both were adapted to the expression proposed previously. The initial rate and the damping factor of the growth were inversely proportional to the wall thickness of myelin tubes. PMID- 1423808 TI - Interactions of aminoglycoside antibiotics with phospholipids. A deuterium nuclear magnetic resonance study. AB - The effect of several aminoglycoside (AG) antibiotics on aqueous multilamellar dispersions of mixtures of phosphatidylinositol (PI) and deuterated phosphatidylcholine (PC) has been studied by deuterium (2H) NMR. Isepamicin and amikacin gave rise to no significant changes in 2H-NMR lineshape relative to that of the lipid mixture without antibiotic. Both kanamycin A and B, which have a greater affinity for PI than the other two antibiotics examined in this study, induced temperature-dependent changes in 2H-NMR lineshapes and associated spectral moments. The results are consistent with an antibiotic-induced lateral phase separation giving rise to PC-enriched domains free of drug and PI-AG domains. These effects are correlated with the inhibitory potency of aminoglycosides towards PC degradation. PMID- 1423810 TI - A histological study of changes in the lingual papillae of streptozotocin-induced diabetic rats. AB - This study examined the effect of experimental diabetes mellitus on the dorsal tongue of rats which were made diabetic by tail-vein injections of streptozotocin (50 mg/kg) and then raised for either 5 or 10 months. Lingual papillae were observed by scanning electron microscopy (SEM) and light microscopy. Morphological changes in lingual mucosal capillaries in 10-month diabetic rats were observed by electron microscopy (TEM). In the study of cellular movement in the lingual dorsal epithelium, bromodeoxyuridine (BrdU) was applied as a tracer for studying DNA replication. In diabetic rats, lingual papillae showed morphological atrophic changes. The lingual mucosal capillaries' alterations included endothelial cells with numerous cell projections into the lumen, degenerated cell organs, increased basement membrane width, and narrowed capillary lumen. BrdU labeling index among the basal cells was reduced in diabetic rats which indicates a possible retardation of their epithelial-tissue activity. In diabetes mellitus, direct metabolic disturbances to the epithelia because of insulin deficiency first occurred, successively diabetic microangiopathy appeared on the lingual mucosal capillaries. The appearance of diabetic microangiopathy caused tissue hypoxia, which induced atrophic changes to the epithelia. PMID- 1423811 TI - Bradykinin-induced responses in hamster submandibular ganglion cells. PMID- 1423812 TI - Hyperpolarization in hamster submandibular ganglion cell mediated by dopamine D2 receptors. PMID- 1423813 TI - Osteogenic activity of cells from dental pulp, periodontal ligament, bone marrow and muscle in vitro: an ultrastructural study and alkaline-phosphatase activity. AB - Dental pulp, periodontal ligament, bone marrow and muscle tissue from the same rat were cultured in vitro in order to investigate their osteogenic activity by transmission electron microscope. Immunohistochemical methods with various antibodies were utilized and alkaline-phosphatase (ALPase) activities of these cells were also measured biochemically. Dental pulp cells were stellate in shape, showed an intense ALPase reaction, and had lipid-like droplets. Periodontal ligament cells were composed of spindle fibroblasts and epithelial cells. The former revealed a positive reaction for ALPase and possessed microfilaments. Bone marrow cells were spindle shaped, resembling fibroblasts, but some of them were similar to osteoblasts. Muscle cells were long, slender in shape, and showed no positive reaction for ALPase. The cells from pulp tissue showed the highest activity of ALPase, followed by periodontal ligament and bone marrow; there was no activity in muscle tissue. All the cells except the epithelial-like cells of the periodontal ligament and muscle cells were positive in reaction with ALPase which is a marker for osteogenic cells, and vimentin which is a marker of fibroblastic characteristics. Osteogenic activity and cellular differentiation of these cells were discussed. PMID- 1423814 TI - Hemostasis and malignancy: an overview. PMID- 1423815 TI - Biomechanical interactions of cancer cells with the microvasculature during hematogenous metastasis. AB - Different aspects of hematogenous metastasis are discussed from the viewpoint of biomechanics. The processes considered include the role of primary tumor pressure, cell locomotor forces and degradation, in invasion of tissues and intravasation by cancer cells. Consideration of the fluid dynamics of cancer cell movement along capillaries lead to the view that in vivo, arrest is primarily due to mechanical trapping of cancer cells, and that the pathobiologic role of so called adhesion molecules is not mainly in the arrest and adhesion of cancer cells, but rather in stimulating their proliferation by signal induction. As a consequence of deformation from spherical-to-cylindrical shape in the microvasculature, demands for increased surface membrane area leads to increases in surface membrane tension above critical levels for rupture, and the cancer cells are rapidly and lethally damaged. The possibility is briefly discussed of increasing the susceptibility of circulating cancer cells to mechanical trauma, as a form of anti-metastatic therapy. PMID- 1423816 TI - Hemostatic alterations in cancer patients. AB - Nearly all patients with cancer manifest laboratory evidence of hypercoagulability and some develop clinical thromboembolic disease (TED). Routine laboratory studies of blood coagulation have been performed in several large, prospective trials of the use of anticoagulant drugs in cancer treatment. The results of these studies, as well as data from several smaller studies of more sensitive tests of hypercoagulability [e.g. fibrinopeptide A (FPA); thrombin antithrombin (TAT) complexes; prothrombin fragment F1 + 2)], indicate that the levels of some clotting proteins parallel disease activity. However, no studies of sound methodologic design have yet been performed to indicate that any of these tests of blood coagulation can serve as adequate predictors of TED in patients with cancer. In addition to the important role played by tumor-related procoagulants, several other mechanisms may be involved in the pathogenesis of thromboembolic events in patients with cancer, including stasis and endothelial damage. Considerable variability in the relative importance of these mechanisms in the pathogenesis of TED may exist among patients with different types of cancer. The risk for TED associated with surgical procedures in cancer patients is substantial and prophylactic antithrombotic therapy should be considered for most of these patients. Chemotherapy and hormonal therapy of cancer probably increases the likelihood of TED, particularly in those subjects with indwelling venous catheters. This risk has been particularly well-studied in patients with breast cancer treated with tamoxifen plus cytotoxic drugs. The pathogenic mechanisms may be complex but vascular injury is likely as a proximate cause of venous access catheter thrombosis and can be prevented with low dose coumadin therapy. The utility of low dose coumadin anticoagulation in reducing the risk for TED during breast cancer treatment is unknown but is currently being tested in a large, multiinstitutional study. Since chronic coumadin anticoagulation of cancer patients, and single pulse dose heparin prior to intravenous chemotherapy, both prevent thrombin generation, these agents may be of use in reducing the risk of chemotherapy-associated thrombosis. Prophylactic anticoagulation should be considered for high risk patients. PMID- 1423817 TI - Tissue factor as a tumor procoagulant. AB - Tissue factor is a cell surface glycoprotein responsible for initiating the extrinsic pathway of coagulation. Many tumor cell homogenates and intact tumor cells have been shown to contain tissue factor activity. Immunohistochemical studies show that many tumors associated with Trousseau's syndrome express tissue factor on their cell surfaces. Tumor cells shed membrane fragments which carry tissue factor that can account for the activation of the clotting system. Tumor cells also produce soluble substances that can induce tissue factor expression on host cells, such as endothelium and monocytes, at sites distant from the tumor. Although, all the functional TF molecules are localized on the outer cell membrane in many tumor cells, the procoagulant activity on the intact cell surface is largely dormant and can be greatly enhanced upon cell injury or damage. Tissue factor procoagulant activity on the cell surface can be modulated by alterations in the plasma membrane without loss of cell viability. Tissue factor activity on cell surfaces is largely regulated by a plasma inhibitor, tissue factor pathway inhibitor. This inhibitor binds to both functional and non functional tissue factor/VIIa complexes on the cell surface and prevents non functional tissue factor/VIIa complexes from becoming functional after cell injury or lysis. Heparin, but not warfarin, therapy is effective in preventing the occurrence of devastating thrombotic events in patients with Trousseau's syndrome and the reason(s) for this are still unknown. PMID- 1423818 TI - Non-tissue factor procoagulants in cancer cells. PMID- 1423819 TI - The role of fibrin in tumor metastasis. AB - A volume of data that has accumulated for over a century has suggested that fibrin may facilitate the persistence and progression of malignancy. Techniques that have been developed recently have shown that fibrin is indeed a component of the connective tissue stroma in human malignancy but in only a few tumor types. However, therapeutic intervention studies with drugs that limit thrombin activity or enhance fibrinolysis have shown favorable clinical effects in at least one such tumor type. These favorable findings affirm the concept that cause-and effect relationships do, in fact, exist between thrombin generation with fibrin formation and tumor progression, and suggest that a rational basis exists for the design of future drug intervention trials that target reactions relevant to specific tumor types. These findings also provide a basis for the design of experiments capable of defining further the role of fibrin in the integrity of these tumor types. Because fibrinogen is found much more commonly than fibrin in the connective tissue of a variety of human malignancies, attention might reassumably be directed to determining the possible contribution of this molecule as well as of fibrin to tumor progression. PMID- 1423820 TI - The plasminogen-plasmin system in malignancy. AB - The study of the plasminogen-plasmin system has, in the past, contributed much to the understanding of fibrinolysis and thrombolysis. Attention is now focused on the role of the components of this system in many biologic functions. Findings of uPA, its receptor and its inhibitor in many tumor tissues and tumor cell lines, strongly implicate their involvement in tumor invasion, tumor cell proliferation and metastasis. The characteristics of the plasminogen activators, the uPA receptor and the plasminogen activator inhibitors as well as their expression and regulation in tumors and tumor cell lines are reviewed. PMID- 1423821 TI - Platelets and cancer metastasis: a causal relationship? AB - Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells undergo extensive interactions with various host cells before they establish a secondary metastatic colony. Ample morphological studies have documented the close association of circulating tumor cells with host platelets. Several lines of evidence provide strong support for the concept that tumor cell platelet interactions (i.e., TCIPA) significantly contribute to hematogenous metastasis. Clinically, cancer patients with advanced diseases are characterized by a variety of thromboembolic disorders including thrombocytosis. Pharmacologically, various anti-platelet agents/anticoagulants have demonstrated potent inhibitory effects on tumor cell-platelet interactions as well as spontaneous or experimental metastasis. Experimentally, interference with many of the intermediate steps of tumor cell-platelet interactions has resulted in diminished platelet aggregation induced by tumor cells and blocked cancer metastasis. Platelet interaction with tumor cells is a sequential process which involves two general types of mediators, i.e., membrane-bound molecules (adhesion molecules) and soluble release products. alpha IIb beta 3 integrin receptors present on both platelets as well as on tumor cells and 12(S)-HETE, a 12 lipoxygenase metabolite of arachidonic acid, are prototypical examples of each category. Mechanistically, platelets may contribute to metastasis by: (1) stabilizing tumor cell arrest in the vasculature, (2) stimulating tumor cell proliferation, (3) promoting tumor cells extravasation by potentiating tumor cell induced endothelial cell retraction, and (4) enhancing tumor cell interaction with the extracellular matrix. PMID- 1423822 TI - Adhesion molecules and tumor cell interaction with endothelium and subendothelial matrix. AB - Cancer metastasis poses the greatest challenge to the eradication of malignancy. The majority of clinical and experimental evidence indicates that metastasis is a non-random, organ-specific process. Tumor cell interaction with endothelium and subendothelial matrix constitutes the most crucial factor in determining the organ preference of metastasis. A plethora of cell surface adhesion molecules, which encompass four major families (i.e., integrins, cadherins, immunoglobulins and selectins) and many other unclassified molecules, mediate tumor-host interactions. Adhesion molecules and adhesion processes are involved in most, if not all, of the intermediate steps of the metastatic cascade. Decreased E cadherin expression and increased CD44 expression are clearly correlated with the acquisition of the invasive capacity of primary tumor cells. Similarly, altered expression pattern of many other adhesion molecules such as upregulated expression of the laminin receptors and depressed expression of fibronectin receptors (alpha 5 beta 1) appears to be involved in tumor cell invasion into the subendothelial matrix. Tumor cell-endothelium interactions involve several well defined sequential steps that can be analyzed by the 'Docking and Locking' hypothesis at the molecular level. Tumor cell-matrix interactions are determined by the repertoire of adhesion receptors of tumor cells and the unique composition of organ-specific matrices. Our experimental data, together with others', suggest that the integrin alpha IIb beta 3 is one of the major players in these tumor host interactions. Tumor-host interaction is a dynamic process which is constantly modulated by a host of factors including various cytokines, growth factors and arachidonate metabolites such as 12(S)-HETE. Delineation of the molecular mechanisms of tumor-host interactions may provide additional means to intervene in the metastatic process. PMID- 1423823 TI - Cancer cell interactions with injured or activated endothelium. AB - Blood vessels and lymphatics are the most important pathways for dissemination of cancer cells but the entry and exit of these cells into and from the vasculature requires that they pass through barriers formed by the endothelium and its basement membrane. This review summarizes evidence that this step in metastasis can be regulated by microenvironmental influences which alter the properties of this barrier. These phenomena can be attributed to both 'passive' and 'active' responses of the endothelium. The microvasculature is susceptible to perturbation from environmental agents, host cells and cancer cells. There is clinical and experimental evidence that this can upregulate the metastatic process. Using established animal models of pulmonary microvascular injury it has been shown that endothelial damage promotes the localization and metastasis of circulating cancer cells to the lung and that this effect is lost after endothelial repair. Oxidative stress is an effector of vascular damage in several of the experimental models. While endothelial cells appear to be directly susceptible to free radical attack, basement membranes are not. However, oxidative injury of endothelial cells causes release of proteases which can then degrade the basement membrane. This event is associated with generation of tumor cell chemoattractants and enhances cancer cell invasion of vascular basement membranes in vitro. Vascular endothelial cells are also susceptible to stimulation by systemic mediators including cytokines, thrombin, or endotoxin which induce a series of active responses in the vessel wall. These perturbed endothelial cells synthesize and express cell surface adhesion molecules which can interact with cancer cells. They also release chemoattractants which stimulate cancer cell motility. We postulate that such responses endow the vessel wall with the potential to act as a determinant of metastatic rate. PMID- 1423824 TI - Fatty acid modulation of tumor cell-platelet-vessel wall interaction. AB - Prostaglandins and other eicosanoids have been studied extensively in their physical, biochemical, biophysical and pharmacological aspects. However, studies on their role in tumor progression, especially metastases are relatively recent. Following a brief overview of the history of discovery and metabolism of eicosanoids and other fatty acids, we discuss the functions of these fatty acids (with emphasis on prostacyclin, thromboxane A2, 12-hydroxyeicosatetraenoic acid and 13-hydroxyoctadecadienoic acid) in cell transformation, tumor promotion and particularly in tumor cell metastasis. The relation between these monohydroxy fatty acids and tumor cell metastasis is discussed from three different perspectives, i.e., their effects on tumor cells, on platelets and on endothelial cells. The mechanism of these effects are then addressed at cell adhesion molecule, motility, protease, cell cytoskeleton, protein kinase and eicosanoid receptor levels. Finally, regulation of three key enzymes which generate eicosanoids (phospholipase, prostaglandin endoperoxide synthase and lipoxygenase) is explored. PMID- 1423826 TI - Clinical trials with anticoagulant and antiplatelet therapies. AB - Clinical trials of drugs that influence coagulation and fibrinolysis pathways have been undertaken in patients with malignancy because these pathways are capable of influencing malignant progression. The validity of this concept was originally confirmed in experimental animal models of malignancy. Earlier pilot studies in human disease have been succeeded by definitive prospective randomized clinical trials that have revealed heterogeneity of responsiveness to anticoagulant and fibrinolytic agents that may be attributable to differences in mechanisms of interaction of the tumor cells of various types of malignancy with these pathways in vivo. In certain tumor types studied thus far, increased tumor response rates and prolongation of survival have been observed that suggest the possibility that substantial benefit may be realized from this treatment approach in patients with malignancy. In addition, the availability of newer and potentially more effective therapeutic agents holds promise for even greater gains in previously tested tumor types. The ability to design treatment regimens that correspond to defined mechanisms that pertain to specific tumor types should permit future studies to be designed rationally. Current data suggest that anticoagulant and fibrinolytic agents might reasonably be tested in tumor types characterized by the existence of a tumor cell-associated coagulation pathway with thrombin generation and conversion of fibrinogen to fibrin (such as small cell carcinoma of the lung). By contrast, protease inhibitors might reasonably be tested in tumor types characterized by expression of tumor cell plasminogen activators. Expansion of current views on the possible role of antithrombic drugs in cancer therapy is justified. For example, antithrombotic drugs classified as non-steroidal anti-inflammatory agents may inhibit carcinogenesis while polyanionic drugs with anticoagulant properties, such as suramin and heparin, may inhibit growth factor interactions with cells. Intriguing new opportunities clearly exist for interactions between clinical and basic investigators that may provide both novel biologic insights and improved patient care. PMID- 1423825 TI - Clinical significance of prostacyclin and thromboxane in cancer of the female breast and genital tract. AB - Studies investigating the role of thromboxane A2 and prostacyclin in cancer of the female breast and genital tract are reviewed. Whereas thromboxane A2 was found to promote the tumour growth and metastasis, prostacyclin exerted a protective effect in maintaining vascular and platelet homeostasis. Thus, monitoring of prostacyclin and thromboxane levels in plasma and urine of cancer patients may be essential for the evaluation of tumour growth and metastasis. Of all modulators of thromboxane and prostacyclin biosynthesis, nafazatrom was found to exhibit promising results for the treatment of advanced breast cancer, although its use in the routine therapy is questionable at this stage. PMID- 1423827 TI - Plasmacytomagenesis in mice: model of neoplastic development dependent upon chromosomal translocations. AB - Three model systems of plasmacytomagenesis that are associated with mutations that affect c-myc transcription were discussed. Plasmacytoma induction by chronic peritoneal irritation induced by non-metabolized paraffin oils or plastic objects is strongly influenced by the immune status of the host. BALB/cAn mice must be exposed to natural environmental antigens to develop a high incidence of plasmacytomas. This may be related to T-cell priming. BALB/cAn mice raised under strict SPF conditions are refractory to plasmacytoma induction by pristane. The genotype of the mouse plays an important role in the chronic peritoneal irritation model of plasmacytomagenesis in mice. Only a few of the standard inbred strains are susceptible, notably BALB/cAn and NZB/B1. The genetic basis of susceptibility and resistance has been studied in crosses and congenic strains involving the susceptible BALB/cAn and resistant DBA/2 strains. While several genes play a role in determining resistance at least one resistance gene located on the distal end of Chr 4 reduces the incidence by at least 50% as determined in the BALB/cAn.DBA/2 Fv-1n/n congenic strain. The action of susceptibility and resistance genes is not known; hypothetically these genes could play a role in plasmacytomagenesis by increasing the probabilities of illegitimate exchanges between genes or by influencing the formation of mutations in genes that regulate mitotic cycling. Plasmacytomas appear to develop in the chronic inflammatory tissues induced by these agents. Fundamental unanswered questions are whether these inflammatory tissues provide products such as oxidants in vivo that damage DNA and promote mutagenesis. In the mouse there is a resident self-renewing B cell population that is CD5+. These B cells, which are known to be precursors of normal lamina propria IgA-secreting plasma cells, are directly in contact with the chronic inflammatory process induced by pristane; they may be targets in plasmacytomagenesis. The plasmacytomas that develop by the peritoneal mode of induction all have chromosomal translocations that directly or indirectly activate c-myc. The predominant MACTR found in 90% of these tumors is T(12;15) in which a heavy-chain switch region sequence is joined to the 5' region of c-myc. The evidence strongly suggests that the translocation develops in a late mature B cell that is in the process of isotype switching. An unanswered question is whether the switching associated T(12;15) takes place in a B cell that is exposed to the inflammatory microenvironment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423828 TI - Sulfation of hydroxylamines and hydroxamic acids in liver cytosol from male and female rats and purified aryl sulfotransferase IV. AB - Sulfation activity towards hydroxamic acids and hydroxylamines was determined in liver cytosols for juvenile and adult males and female rats, as well as in purified rat liver aryl sulfotransferase IV preparations. Sulfation activity towards the hydroxamic acids N-hydroxy-2-acetylaminofluorene, N-hydroxy-2 acetylaminophenanthrene, N-hydroxy-4-acetylaminobiphenyl, N-hydroxy-4'-fluoro-4 acetylaminobiphenyl, N-hydroxy-2-acetylamino-5-phenylpyridine, was higher in cytosols derived from adult males (two or three times) than in those from adult females and juveniles (both sexes). N-Hydroxy-2-acetylamino-3-methyl-5 phenylpyridine (N-OH-2AAMPP), however, was poorly sulfated by any of the cytosols. Sulfation activity towards the hydroxylamines N-hydroxy-2 aminofluorene, N-hydroxy-2-aminophenanthrene, N-hydroxy-4-aminobiphenyl, N hydroxy-4'-fluoro-4-aminobiphenyl was much lower. N-Hydroxy-2-amino-5 phenylpyridine (N-OH-2APP), however, was sulfated much better than the other hydroxylamines. No higher sulfation activity in adult male cytosols for hydroxylamines was found, except for N-OH-2APP and N-hydroxy-2-amino-3-methyl-5 phenylpyridine (N-OH-2AMPP). Purified aryl sulfotransferase IV (AST IV) converted all hydroxamic acids; N-OH-2AAMPP was a poor substrate. Of the hydroxylamines only N-OH-2APP and N-OH-2AMPP were conjugated. These results suggest that hydroxylamines and hydroxamic acids are converted by different sulfotransferases in the rat in vivo. They also indicate that AST IV may be the major enzyme responsible for sulfation of a variety of aromatic hydroxamic acids in the male rat liver. The results presented here are discussed in relation to the carcinogenic effects of some of these compounds. PMID- 1423830 TI - The role of the human acetylation polymorphism in the metabolic activation of the food carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). AB - The metabolic activation of the heterocyclic food carcinogen 2-amino-3 methylimidazo[4,5-f]quinoline (IQ) by two human cytochrome P450 monoxygenases (P4501A1 and P4501A2) and two human N-acetyltransferases (NAT1 and NAT2) was investigated. Various combinations of these enzymes were functionally expressed in COS-1 cells. DNA adducts resulting from the activation of IQ were assayed quantitatively by the 32P-postlabeling procedure. The highest adduct frequency was observed in cells expressing both CYP1A2 and NAT2. CYP1A2 in combination with NAT1 was 3-6 times less active. When expressed alone these enzymes gave rise to low adduct frequencies. Experiments with N-acetyl-IQ as substrate suggest that NAT1 and NAT2 in addition to their known role in N-acetylation display arylhydroxamic acid N, O-acetyltransferase (AHAT) activity. Quantitative differences in adduct formation between IQ and N-acetyl-IQ indicated that metabolic activation of these arylamines preferentially occurs by P4501A2 catalyzed N-hydroxylation followed by O-acetylation mediated through NAT1 and/or NAT2. These data, in combination with the known genetic polymorphism of NAT2, may explain the clinical observation that the acetylation polymorphism constitutes a risk factor in the carcinogenic activation of environmental mutagens. PMID- 1423829 TI - Microsome-mediated transacetylation and binding of N-hydroxy-4-aminobiphenyl to nucleic acids by hepatic and bladder tissues from dog. AB - Microsome-mediated metabolism of [3H]4-aminobiphenyl (ABP) and binding of [3H]N hydroxy-4-aminobiphenyl (N-OH-ABP) to nucleic acids by dog hepatic and bladder microsomes were investigated. HPLC analysis of the ethyl acetate extracts of hepatic microsomal incubates of [3H]ABP in the presence of 4-acetylaminobiphenyl (AABP), N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), or acetyl coenzyme A (AcCoA) as acetyl donors showed the formation of [3H]AABP, suggesting that microsomes catalyze N-acetylation of ABP involving transacetylation. Dog hepatic microsomes also catalyzed the binding of [3H]N-OH-ABP to RNA in the presence of AABP, N-OH AABP or AcCoA, and the binding was blocked by paraoxon, an inhibitor of microsomal deacetylases. Binding of [3H]N-OH-ABP to DNA was catalyzed also by dog hepatic microsomes, and the extent of binding was 266, 156 and 135 pmol/mg DNA for AABP, N-OH-AABP and AcCoA as acetyl donors respectively. HPLC analyses of the DNA hydrolysates showed that the major adduct formed was N-(deoxyguanosine-8-yl) 4-aminobiphenyl, based on mobility of the adduct in comparison with the synthetic standard. The acetyl adduct N-(deoxyguanosine-8-yl)-4-acetylaminobiphenyl was not detected in the DNA hydrolysates. Adduct profiles obtained from 32P-postlabeling of DNA samples from the microsome-mediated binding of [3H]N-OH-ABP showed similarities to the profile obtained previously from the chemical interaction of N-OH-ABP with DNA under acidic conditions, suggesting that the microsome-mediated binding of N-OH-ABP may proceed via formation of aryl nitrenium ions as the ultimate electrophilic species. Microsomes from dog bladder also catalyzed the binding of [3H]N-OH-ABP to RNA and DNA in the presence of AABP, N-OH-AABP or AcCoA as acetyl donors, though the levels of binding were less than those observed with hepatic microsomes. The prevalence of these acetyl transferases in the target organs for ABP and AABP carcinogenesis raises the possibility that metabolic activation of the proximate metabolite N-OH-ABP could occur directly in these tissues and these reactions could play a critical role in the initiation of cancers. PMID- 1423831 TI - DNA adducts and induction of sister chromatid exchanges in the rat following benzo[b]fluoranthene administration. AB - Benzo[b]fluoranthene (B[b]F) was administered (100 mg/kg by i.p. injection) to male Sprague--Dawley rats. Lungs, livers and peripheral blood lymphocytes (PBLs) were harvested 1, 3, 5, 7, 14, 28 and 56 days after treatment. Several DNA adducts were observed in each tissue, with maximal levels occurring at approximately 7 days after treatment. Lung DNA exhibited consistently higher adduct levels than liver or PBL DNA. At 56 days after B[b]F administration, the adducts in liver and PBL DNA were present at < 10 amol/microgram DNA, while in lung there were 100 amoles/microgram DNA. No significant differences were observed between tissues in the types of adducts produced. Co-chromatography with synthetic standards showed that only a minor adduct produced in vivo is derived from trans-9,10-dihydro-9,10-dihydroxybenzo[b]fluoranthene-11,12-oxide. Sister chromatid exchanges (SCEs) from whole blood cultures were significantly increased relative to concurrent controls between 1 and 14 days after B[b]F administration, with maximum levels at 14 days. By 28 days after treatment, SCEs had essentially returned to control levels. SCE induction did not correlate with the amount of B[b]F--DNA adducts remaining in the PBLs at harvest time. PMID- 1423832 TI - Effect of varying the type of fat in a semi-purified AIN-76A diet on cellular proliferation in the mammary gland and intestinal crypts in female Swiss Webster mice. AB - Young virgin female Swiss Webster mice were fed AIN-76A semi-purified diets containing equal weights of different fats for approximately 30 days. Using [3H]thymidine radioautography, it was established that mice fed 100% lard or high levels of fish oils (menhaden oil or cod liver oil) developed elevated cellular proliferation in the duct cells of the mammary gland and an increased number of labeled cells/crypt in the crypts of the colo-rectum accompanied by an increase in the size of the proliferative compartment. A possible inverse correlation between the level of [3H]thymidine labeling in the mammary gland, but not in the colo-rectum, and the linoleic acid content of individual diets may help to explain the significance of these observations. The effect of adding an antioxidant mixture to these diets was to reduce the excess proliferation induced in the intestinal crypts by lard or fish oil to the level induced by soybean oil, but only partially so in the duct cells of the mammary gland. PMID- 1423833 TI - Depletion of O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine in three dimensional collagen cultures of normal human breast epithelial cells. AB - O6-Alkylguanine--DNA alkyltransferase (AGT) is a protein which removes the promutagenic O6-alkylguanine lesion induced in DNA by alkylating agents. Our results demonstrate that freshly isolated organoids from reduction mammoplasty specimens contain significant levels of AGT activity. AGT activity in breast epithelial cells shows interindividual variation. Constitutive levels of AGT activity remain unchanged during short-term serum-free culture of breast epithelial cells inside three-dimensional rat-tail collagen gel matrix. In the present study, we optimized conditions for depleting AGT activity in human breast epithelial cells cultured in three-dimensional collagen gel matrix using O6 methylguanine and O6-benzylguanine which are substrates for AGT. AGT activity was efficiently inactivated by exposure of cells to O6-methylguanine or O6 benzylguanine. Inactivation with O6-benzylguanine was more rapid, of greater magnitude and consistency and occurred at lower concentrations than with O6 methylguanine. Near-complete inactivation (> 99.5%) of AGT activity was reproducibly achieved with 50 microM O6-benzylguanine. In contrast, 500 microM O6 methylguanine was needed to obtain a maximal effect and this reduced AGT activity by only 53-93% of control. Within 30 min of adding the free base, 50 microM O6 benzylguanine depleted 95% of the levels of AGT compared to 30% inhibition with 500 microM O6-methylguanine. The profile for restoration of AGT activity was different following a 24 h incubation and subsequent removal of each of the guanine derivatives. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6-benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. AGT activity levels remained undetectable for at least 2 days after removal of 50 microM O6 benzylguanine from the medium and recovered to only 53% of control values after an additional 3 days. In contrast, following removal of 500 microM O6 methylguanine, the activity was restored from its nadir of 16% of control values reaching pretreatment levels after 5 days. These results suggest that treatment with O6-benzylguanine may be used to modulate the incidence of transforming mutations in cultured human breast epithelial cells treated with chemical carcinogens which give rise to O6-alkylguanine adducts. PMID- 1423834 TI - Peroxisome proliferation and resistance to hydrogen peroxide in rat hepatocytes: is development of resistance an adaptation to cytotoxicity? AB - In this work the resistance of peroxisome-proliferated hepatocytes to hydrogen peroxide (H2O2) has been studied. The question has been raised as to whether this resistance is a response to cytotoxicity. In an initial series of experiments, hepatocytes were isolated from rats that had been treated with nafenopin (NAF hepatocytes). Isolated cells were exposed to a H2O2-generating system or to H2O2 in pulses. The ability to attach to collagen was used as a toxicological endpoint. Loss of attachment was found to be correlated to glutathione (GSH) depletion, and NAF-hepatocytes were more resistant to GSH depletion and to loss of attachment induced by H2O2 than were control hepatocytes. NAF-hepatocytes were not resistant to hydroquinone or to adriamycin. It was also indicated that this resistance was related to an altered metabolism of H2O2, less dependent on GSH. In a second series of experiments, hepatocytes from altered hepatic foci-bearing rats, treated with nafenopin or di(2-ethylhexyl)phthalate (DEHP), were used. This model was used in an attempt to monitor the development of resistance in different subpopulations of hepatocytes. It was found that the majority of hepatocytes developed resistance towards H2O2, and that, for example, foci marker positive hepatocytes were as resistant as marker-negative cells. In control experiments with this model, it was found that marker-positive cells were more resistant towards diethyl maleate (DEM) or phorone than were marker-negative cells. In addition to demonstrating the validity of the model, these control experiments indicate an increased steady-state level of H2O2 in cells from peroxisome proliferator-treated rats. Other control experiments suggested that a low GSH-peroxidase activity protected from, rather than aggravated, the effect of peroxisome proliferation on marker-negative and GSH-depleted cells. It is concluded that H2O2 metabolism may affect the function of collagen receptors, but that a shift in H2O2 metabolism, so that it becomes less dependent on GSH, conferred resistance to this effect. The apparent non-focal induction of resistance to peroxisome proliferators, as opposed to the focal induction of resistance induced by most liver carcinogens, may explain the lack of development of gamma-glutamyltranspeptidase-positive foci in peroxisome proliferator-treated rats. PMID- 1423835 TI - Analysis of residual amino acid--DNA crosslinks induced in intact cells by nickel and chromium compounds. AB - Chinese hamster ovary cells were incubated with radioactive amino acids, the DNA was isolated by standard proteinase K/phenol/chloroform extraction and residual amino acids complexed to the DNA were examined as an index of metal induced DNA protein crosslinks. Using this method, both chromate and nickel caused residual histidine and cysteine to be complexed with the DNA isolated from metal-treated cells. In the case of chromate, a number of amino acids were studied and Tyr, Thr and Cys were found to be complexed to DNA at a level (above the untreated control) that was statistically significant. Stability studies indicated that some of the chromate-induced DNA-protein complexes were mediated by direct participation of chromium(III), whereas others that were resistant to dissociation by EDTA and mercaptoethanol did not seem to involve direct chromium(III) participation. A significant portion of the cysteine complexed to DNA by chromate was believed to involve glutathione since treatment of cells with cycloheximide did not decrease chromate-induced cysteine-DNA crosslinks. In the case of nickel, most of the stable DNA-protein crosslinks did not involve direct metal participation and were probably oxidatively mediated by Ni(II)/Ni(III) redox cycling. These findings present new methodology for analysis of DNA-protein crosslinks by examination of residual amino acids associated with the DNA. This method should be highly sensitive and will yield important information about the mechanism of metal-induced DNA-protein crosslinks. PMID- 1423836 TI - Expression of O6-methylguanine--DNA methyltransferase and uracil--DNA glycosylase in human placentae from smokers and non-smokers. AB - DNA repair capacity is likely to be a critical factor in mutagenesis and carcinogenesis, as well as for the response to some cytostatics. We have studied inter- and intra-individual variation in the activities of O6-methylguanine--DNA methyltransferase (O6-MT) and uracil--DNA glycosylase (UDG) in 35 placentae from smokers and non-smokers. The maximum interindividual variation in the activities of O6-MT and UDG were 8.3- and 7.7-fold, respectively. The corresponding intraindividual variations were 2.7- and 3.3-fold. Generally, a high level of O6 MT activity was accompanied by a high O6-MT mRNA level, but no such correlation was seen for UDG. These results were not due to degradation of the enzymes or mRNAs after delivery. No correlation between the activities of O6-MT and UDG was observed, indicating that they are differentially regulated. A 1.4-fold (P < or = 0.05) higher activity of O6-MT was observed in smokers as compared to non smokers, indicating a small, but statistically significant difference. No significant difference was observed for UDG. Our results demonstrate that DNA repair capacities vary largely between different individuals, and that environmental factors may modulate the expression of DNA repair enzymes. PMID- 1423837 TI - 11-Methylbenzo[a]pyrene: bay region distortions. AB - Substitution of a methyl group in the 11-position of benzo[a]pyrene (B[a]P) enhances its carcinogenicity. An X-ray crystallographic determination of the three-dimensional structure of 11-methylbenzo[a]pyrene (11-MeB[a]P) shows that steric overcrowding in the bay region is relieved somewhat by distortions of the bay-region bond angles in the plane of the ring system. A comparison with the structure of 7,12-dimethylbenz[a]anthracene (DMBA), which shows out-of-plane distortions to relieve such strain, shows that, in general, H...H intramolecular interactions between neighboring rings in a polycyclic aromatic hydrocarbon are the primary determinants of the nature of the molecular distortions as a result of steric overcrowding (mainly in-plane for 11-MeB[a]P and mainly out-of-plane for DMBA). The 11-MeB[a]P molecule exhibits considerable flexibility as evidenced by slightly different conformations in the two molecules found in the asymmetric unit of the crystal. One molecule is fairly flat with bond angle distortions in the bay region, while the other is slightly buckled as a result of some twist (15 degrees) in the bay region. Computer modeling indicates that steric overcrowding as a result of the bay-region 11-methyl group may affect the conformation of the ring that bears the diol and epoxide groups in the anti-diolepoxide. The nature of this distortion may, in turn, provide a clue to the reason for the greater carcinogenicity of B[a]P when methylated at the 11-position in the non-benzo bay region site. In addition, the 11-methyl group, because of its bulk, may affect the orientation of the polycyclic hydrocarbon as it lies between the nucleic-acid bases when covalently bound to DNA. PMID- 1423838 TI - Copper-dependent site-specific mutagenesis by benzoyl peroxide in the supF gene of the mutation reporter plasmid pS189. AB - Benzoyl peroxide (BzPO) enhances tumor promotion and malignant conversion in mouse epidermis. DNA damage may contribute to these processes. BzPO reacts with Cu(I) to produce the benzoyloxyl radical, which in turn causes strand breaks in plasmid DNA. In this study we investigated whether BzPO with or without Cu(I) caused promutagenic DNA damage in the supF gene of the mutation reporter plasmid pS189 replicating in human Ad293 cells. Exposure of pS189 in vitro to BzPO (0.1-1 mM) inhibited plasmid replication; however, addition of Cu(I) (0.1 mM) did not augment BzPO-induced plasmid toxicity. Exposure to BzPO with or without 0.1 mM Cu(I) was also associated with a concentration-dependent increase in mutation frequency, up to > 100-fold above the spontaneous mutation frequency. Supplemental Cu(I) was not required for mutagenesis; however, it both raised the maximal mutation frequency observed and lowered the threshold concentration of BzPO necessary to discern mutagenesis above the spontaneous background. Neither the hydroxyl radical scavengers mannitol or DMSO, the spin trap N-tert-butyl alpha-phenylnitrone, nor reduced glutathione altered BzPO/Cu(I)-induced mutagenesis; however, mutagenesis was suppressed by the chelator EDTA. Twenty four of 32 individual BzPO/Cu(I)-induced mutants characterized by sequencing contained point mutations; 22/25 point mutations occurred at G-C base pairs. There were five large deletions and four small deletions. Three additional BzPO induced mutants contained four point mutations, all occurring at G-C base pairs. Two BzPO/Cu(I)-induced mutational clusters at d(pGGG)-d(pCCC) sites were observed. These data suggest that BzPO may interact with Cu(I) bound to G-C base pairs in DNA to produce site-specific promutagenic DNA damage. PMID- 1423839 TI - Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes. AB - An acetyltransferase-overexpressing strain of Salmonella typhimurium (NM2009) has been used to investigate roles of human liver microsomal cytochrome P450 (P450) enzymes in the activation of carcinogenic nitrosamine derivatives, including N nitrosodialkylamines and tobacco-smoke-related nitrosamines, to genotoxic products. Studies employing correlation of activities with several P450-dependent monooxygenase reactions in different human liver samples, inhibition of microsomal activities by antibodies raised against human P450 enzymes and by specific P450 inhibitors, and reconstitution of activities with purified P450 enzymes suggest that the tobacco-smoke-related nitrosamines 4-(methylnitrosamino) 1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and N-nitrosonornicotine (NNN) as well as N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) are oxidized to genotoxic products by different P450 enzymes, particularly P450 2E1 and 2A6. The activation of NDMA and NNN by liver microsomes was suggested to be catalyzed more actively by P450 2E1 than by other P450 enzymes because the activities were well correlated with NDMA N demethylation and aniline p-hydroxylation in different human samples, and purified P450 2E1 had the highest activities in reconstituted monooxygenase systems. The relatively high contribution of P450 2A6 to the activation of NDEA and NNK was supported by the correlation seen with coumarin 7-hydroxylation in human liver microsomes, and antibodies raised against P450 2A6 inhibited both activities by approximately 50%. P450 3A4, 2D6 and 2C enzymes appear not to be extensively involved in the activation of these nitrosamines as judged by several criteria examined. Thus, this work indicates that several P450 enzymes, particularly P450 2E1 and 2A6, catalyze metabolic activation of nitrosamine derivatives including N-nitrosodialkylamines and tobacco-smoke-related nitrosamines in human liver microsomes. PMID- 1423840 TI - Identification and quantitative detection of isomeric benzo[a]pyrene diolepoxide- DNA adducts by low-temperature conventional fluorescence methods. AB - The pyrene-like fluorescence of adducts derived from the covalent binding of (+/ )-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene [+/-] anti-BPDE] to DNA increases in intensity by factors of 20 or more as the temperature is lowered from ambient to approximately 100 K. This effect is primarily associated with the strong quenching of the pyrene-like fluorescence of BPDE-deoxyguanosyl adducts at room temperature, and the suppression of the electron-transfer quenching mechanism at 100 K. In contrast, the fluorescence of BPDE-deoxyadenosyl adducts is not quenched at ambient temperatures, and the fluorescence yields of (+/-)-anti-BPDE-poly(dA-dT).(dA-dT) adducts increases by only a factor of 2 in this same temperature range. Utilizing an internal fluorescein fluorescence standard to correct for differences in light scattering and variations in instrumental factors, a fluorescence method is described for quantitatively determining the levels of benzo[a]pyrene diolepoxide derivatives covalently bound to cellular DNA at 100 K. The method is illustrated with (+/-) reverse-BPDE [(+/-)-trans-9,10-dihydroxy-anti-7, 8-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene]. Adduct levels as low as 10 pmol in a 400 microliters sample volume can be detected and identified from their excitation and fluorescence emission spectra using a conventional and commercially available fluorometer. In the case of modified DNA extracted from BPDE-treated Chinese hamster ovary cells or from mouse skin (approximately 1 BPDE residue/20,000 bases), such an analysis requires only 100 micrograms of DNA. Conformationally different adducts derived from the binding of the isomeric (+/-)-anti-BPDE, (+/-) reverse-BPDE or (+/-)-syn-BPDE to cellular DNA can be distinguished by their low temperature fluorescence excitation spectra. Specifically, the quasi-intercalated site I BPDE adducts (believed to be associated with cis-addition stereochemistry) can be distinguished from site II adducts situated at external BPDE binding sites (trans-addition stereochemistry). These results suggest that the fates of these conformationally different BPDE-DNA adducts, e.g. due to enzymatic repair, can be monitored as a function of time in DNA extracted from intact, functioning cells. PMID- 1423842 TI - Detection and quantitation of dG-AAI and dA-AAI adducts by 32P-postlabeling methods in urothelium and exfoliated cells in urine of rats treated with aristolochic acid I. AB - Analysis of aristolochic acid I (AAI)-DNA adducts in exfoliated cells in urine, urothelium and entire urinary bladder were studied after oral administration of five daily doses (10 mg/kg body wt) AAI for 3 months to rats. The two major adducts excreted in urine are presumably identical to the two main adducts formed in vitro and in vivo in different organs in the rat, which have previously been characterized in vitro as 7(-deoxyguanosin-N2-yl)-aristolactam I and 7( deoxyadenosin-N6-yl)-aristolactam I. Urine samples were collected on dry-ice, subsequently pooled and purified according to the protocol of Kadlubar and co workers. DNA was isolated, digested and AAI-DNA adducts of exfoliated cells in urine and urothelium of rats were detected and quantitated by enhancement methods of the 32P-postlabeling assay, namely nuclease P1 enrichment or butanol extraction. Autoradiograms indicated that adduct patterns in DNA derived from exfoliated cells in urine were very similar to those obtained from DNA isolated from tissues. Quantitative analysis of adducts revealed adduct levels declining for both adducts from DNA isolated from urothelium to DNA isolated from the entire urinary bladder to DNA isolated from exfoliated cells in urine. In general, count rates of two predominant AAI adducts were enhanced by butanol extraction approximately 3- to 8-fold when compared with the nuclease P1 digestion technique. The identity of the two major adducts was confirmed by co chromatography with eluted spots from in vivo adducts by comparing mobilities on poly-(ethyleneimine)-cellulose plates. Microbiological investigations of the urine revealed no gross contamination with bacteria, so that the isolated DNA supposedly originated from exfoliated urothelial cells. This study indicates that 32P-postlabeling analysis can be used to monitor non-invasively the formation of carcinogen-DNA adducts in animals or humans exposed to carcinogens. PMID- 1423841 TI - Influence of caffeic acid and other o-dihydroxybenzene derivatives on N-methyl-N' nitro-N-nitrosoguanidine-initiated rat forestomach carcinogenesis. AB - Promotion effects of the o-dihydroxybenzene derivatives, protocatechuic acid (PCA), dopamine hydrochloride (DAH), dl-dopa and caffeic acid on forestomach and glandular stomach carcinogenesis were investigated in rats pretreated with N methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 20 male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later than received diet containing 1.5% PCA, 1.5% DAH, 1.5% dl-dopa or 1% caffeic acid or basal diet alone for 51 weeks and then killed. Other groups of 10 15 rats were given PCA, DAH, dl-dopa or basal diet alone without the MNNG pretreatment. On histological assessment, the incidences of forestomach papillomas and squamous cell carcinomas were significantly enhanced in the group treated with caffeic acid (95 and 100%) as compared with the control values (35 and 10%). Although the incidence was not different, the number of papillomas per rat in the group given DAH (0.79 +/- 0.79) was also significantly increased (0.35 +/- 0.49). PCA and dl-dopa treatments did not modify the development of neoplastic lesions in the forestomach epithelium to any significant extent. None of the four chemicals enhanced glandular stomach carcinogenesis. The results thus demonstrated that whereas caffeic acid and DAH respectively, exert strong and weak promotion activity for rat forestomach carcinogenesis this promotion potential is not shared by all dihydroxybenzene derivatives. An influence of substituents in the para position in addition to the o-dihydroxy moiety is indicated. PMID- 1423843 TI - Inhibition of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and DNA adducts by garlic powder. AB - The present studies determined the influence of dietary supplements of garlic powder (0, 1, 2 or 4%) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors and on the in vivo occurrence of mammary DMBA-DNA adducts in rats. Diets were offered 2 weeks before and 2 weeks following DMBA treatment (25 mg/kg body wt). An additional group was fed the 2% garlic powder diet throughout the 20 week study. Although food intake and weight gain were not influenced, dietary garlic powder supplementation did significantly delay the onset of first tumors (P < 0.01) and did reduce the final mammary tumor incidence (P < 0.01). Consumption of garlic powder also significantly depressed the in vivo binding of DMBA to mammary cell DNA. Binding of both anti- and syn-dihydrodiol epoxides to DNA was depressed in rats fed supplemental garlic powder. The activity of glutathione S-transferase (GST) in mammary and liver tissue from rats fed 2% dietary garlic powder was higher than observed in tissues from rats fed the basal diet. No further increase in GST activity occurred when the dietary garlic content was increased from 2 to 4%. Final mammary tumor incidence was found to correlate positively with total DMBA-DNA binding and the quantities of individual DMBA-DNA adducts. The present studies demonstrate that garlic powder is effective in inhibiting DMBA-induced mammary tumors, possibly by reducing DMBA-DNA binding. PMID- 1423844 TI - Effect of dietary protein level on aflatoxin B1 actions in the liver of weanling rats. AB - The hepatocarcinogenic responses of rats to aflatoxin B1 (AFB1) are believed to depend on microsomal activation of the toxin, followed by macromolecular binding. Dietary protein insufficiency is reported to reduce the level of microsomal metabolism, and therefore would be expected to reduce the AFB1-induced carcinogenicity. Indeed, diminished hepatocarcinogenicity in low-protein diet fed weanling rats that had received AFB1 has been reported. In the present study, carcinogenicity and other toxic effects of AFB1 (0.5 p.p.m.) fed to weanling male Fischer F344 rats on a low-protein diet (5%) or normal-protein (20%) diet for up to 8 weeks were examined. In our study, in contrast with the previous report, all animals that had survived some initial toxicity were found to have developed hepatic tumors or hyperplastic gamma-glutamyltransferase-positive foci a year later. The low-protein diet also produced sub-acute toxicity after AFB1 exposure in the weanling rats, leading to severe histological changes, and the death of about half the animals after 3-4 weeks of exposure. Animals fed an AFB1 containing normal-protein diet also exhibited AFB1-induced hepatocarcinogenicity, but not the sub-acute toxicity. The levels of hepatic enzymes involved in AFB1 metabolism were examined in animals fed the low- or normal-protein diets in the absence of AFB1. The low-protein diet, fed to 3 week weanlings for the subsequent 5 weeks, decreased hepatic cytochrome P450 levels, as well as the in vitro capacity of microsomal fractions to form AFB1-8,9-dihydrodiol, an index of AFB1 8,9-epoxide formation. Rats on a normal-protein diet did not show these changes. This discrepancy between the observed increase in sub-acute toxicity and decrease in microsomal activities in the low-protein fed animals implies that the toxic effects observed in these rats were not directly related to metabolic activation of the toxin. In contrast to the diminished microsomal in vitro AFB1 activation, however, in vivo AFB1-DNA adduct formation ability in rats receiving the low protein diet in the absence of AFB1 was found to become elevated more rapidly during the 5 week experimental feeding period, compared with animals receiving the normal-protein diet. This was accompanied by a more rapid fall in the levels of AFB1-glutathione S-transferase isozyme activity in the low-protein fed animals. The results of this study on weanling rats support the importance of AFB1-GSH in protecting against the carcinogenic responses to AFB1, and probably also the sub-acute toxicity of the latter.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423846 TI - Expression of ras oncogene mRNA and protein in aberrant crypt foci. AB - The expression of the ras oncogene in aberrant crypt foci was studied by both in situ hybridization and immunohistochemical approaches. Aberrant crypt foci are hypothesized to represent the earliest identifiable microscopic lesions of colon cancer in rodent colons. Sprague-Dawley male rats were injected with azoxymethane (20 mg/kg s.c.) once. Twelve weeks later, aberrant crypt foci were identified topographically, microdissected and processed for histology. In situ hybridization with an antisense oligomer of c-ras demonstrated increased expression of ras-specific RNA in aberrant crypts compared to normal crypts. A low amount of non-specific hybridization was obtained with the corresponding sense oligomer. The percentage of cells with grains (labeling index) was calculated in early and advanced aberrant crypt foci. This index was also calculated in normal appearing crypts. The labeling indices for the early and advanced aberrant crypt foci were significantly greater than that of normal crypts (18.0 and 25.0 versus 11.9). In the same tissue specimens, immunohistochemical staining for ras p21 with the monoclonal antibody (Y13-259) revealed strong staining intensity in early aberrant crypts (15/22) and advanced aberrant crypts (22/30) compared to normal crypts (3/50). The immunohistochemical results demonstrate the presence of elevated levels of ras p21 in the same tissue as increased levels of ras-specific message. This investigation provides the earliest demonstration of increased expression of the ras oncogene in precursor lesions of colon cancer possessing dysplastic features. PMID- 1423845 TI - Carba-prostacyclin inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transformation in sensitive murine epidermal JB6 cells. AB - The ability of carba-prostacyclin (cPGI2), a stable analog of prostacyclin (PGI2), to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced transformation of JB6 cells was investigated. JB6 cells sensitive (P+) and resistant (P-) to TPA-induced transformation to anchorage-independent growth were plated in soft agar in the presence or absence of cPGI2 for 14-21 days. Transformation frequencies were determined by recording colony numbers. cPGI2 was found to inhibit TPA-induced transformation of P+ cells in a dose-dependent fashion with 1 microM cPGI2 producing approximately 50% inhibition of colonies in soft agar. Our findings are consistent with the hypothesis that TPA-induced transformation in JB6 cell variants is mediated by PGI2 via regulation of adenylate cyclase activity and cAMP accumulation, with resultant inhibition of expression of the transformed phenotype, reflected in anchorage-independent growth. PMID- 1423848 TI - Expression of alpha, mu and pi class glutathione S-transferases in oval and ductal cells in liver of rats placed on a choline-deficient, ethionine supplemented diet. AB - Expression of the alpha, mu and pi class glutathione S-transferases (GSTs) in hepatocytes, oval cells and ductal cells derived from the livers of rats placed on a choline-deficient, ethionine-supplemented (CDE) diet for 5 weeks was investigated. An overall decrease in the expression of alpha and mu class GSTs and an over-expression of pi class GST was observed in the liver after CDE treatment as indicated by Northern blotting analysis. Massive disruption of the liver with oval cell infiltration in the sinusoids throughout the lobule occurred after 5 weeks CDE treatment. 'Duct-like' structures consisting of oval-like cells (ductal cells) with rounder nuclei and more cytoplasm than oval cells within the sinusoids were also apparent. Immunocytochemical analysis revealed that the altered expression of GST in the whole liver is attributed to a differential expression of alpha, mu and pi class GSTs in the different cell types in the liver, including hepatocytes, oval cells around the portal region and among the sinusoids, and oval-like cells (ductal cells) in the 'duct-like' structures. In vitro studies using purified oval-ductal cells and hepatocyte populations confirmed the differential expression of GSTs in the varying cell populations in situ. The expression of the alpha and mu class GSTs in hepatocytes does not appear to be altered by the CDE diet. Heterogeneity in distribution of pi class GST was observed in the hepatocyte population, some hepatocytes were stained strongly while no staining was observed in others. Oval and ductal cells represent two distinct populations displaying different expression of GSTs. Pi class GST was detected in the majority of oval and ductal cells. Alpha class GST was detected in < 5% of the oval cell population and was found in > 50% of the ductal cell population. In contrast, mu class GST was absent in ductal cells and was present in 24% of oval cells around the portal region. This supports the view that ductal cells are not of bile ductal origin since mu GST is present in normal bile duct epithelial cells. Furthermore the change in expression of GSTs in the liver after CDE treatment is attributed to the large increase in oval and ductal cell populations. PMID- 1423847 TI - Adaptation and selection as factors in the spontaneous transformation of NIH-3T3 cells. AB - The effect of calf serum (CS) concentration on the spontaneous transformation of NIH-3T3 cells was investigated. Maintenance of NIH-3T3 cell populations in media containing a low concentration of calf serum (2% CS) increased the proportion of spontaneously transformed cells appearing within a population. Higher CS concentration (10% CS) decreased the proportion of transformed cells in the population. In searching for the reasons for the effect of serum concentration on transformation frequency, three conclusions were reached. (i) Non-focus-forming NIH-3T3 cells exhibit heterogeneity in progression toward transformation. (ii) Low serum concentration can increase the frequency of focus-forming cells within an NIH-3T3 population by decreasing the proliferation of non-focus-forming cells relative to focus-forming cells. (iii) The reproductive selection described in (ii) cannot completely account for the focus-enhancing effects of low serum. Evidence for point (iii) is drawn from focus-forming assays, in 2% CS, for a clone of cells maintained in 10% CS before assay. Cells from this clone made no foci in 50 assays, performed on 5 x 10(6) cells, over a 21 week period. However, maintenance of those same cells in 2% CS for as little as 2 days before assay caused these consistent non-focus formers to make foci. We conclude that the basis for this progression to the focus-forming phenotype is an adaptation to the metabolically constraining 2% CS environment. We propose that this adaptation results from progressive selection of physiological states. PMID- 1423849 TI - DNA adduct levels in congenic rapid and slow acetylator mouse strains following chronic administration of 4-aminobiphenyl. AB - 4-Aminobiphenyl (4-ABP) is a human and mouse bladder carcinogen. Epidemiological studies have shown that individuals with a slow acetylator phenotype, especially those exposed to high levels of carcinogenic aromatic amines, show an increased susceptibility to bladder cancer. In order to determine if a slow acetylator phenotype results in increased DNA damage, congenic mouse strains C57BL/6J and B6.A-Nat(s), which differ genetically at the acetyltransferase (EC 2.3.1.5) locus as homozygous rapid (Natr/Natr) and homozygous slow (Nat(s)/Nat(s)) acetylators respectively, were continuously administered 4-ABP.HCl (55-300 p.p.m.) in their drinking water for 28 days. The levels of covalently bound N-(deoxyguanosin-8-yl) 4-ABP-DNA adducts, which are believed to be critical for the initiation of tumors, were quantitated in the liver and bladder by 32P-postlabeling analysis. The levels of the hepatic DNA adduct increased with dose in both sexes, but were independent of the mouse acetylator genotype. At comparable doses, however, the levels of DNA adducts were 2-fold higher in the liver of the female as compared to the male animals. The DNA adducts also increased with dose in bladder of the male mice, but in contrast to the liver, the adduct levels were approximately 2 fold lower in the bladder DNA of the female mice. Also in contrast to the liver, the levels of bladder DNA adducts were significantly higher (P < or = 0.03) in the phenotypic rapid acetylator females compared to the slow acetylators at both 75 and 150 p.p.m. doses; the median levels of adducts were 10-20% higher in the phenotypic slow acetylator male bladders compared to their rapid acetylator counterparts. The results of these studies are consistent with the increased carcinogenicity of 4-ABP to the liver of female mice and the bladder of male mice. They further suggest that factors other than acetylator phenotype limit the extent of DNA adduct formation from 4-ABP in these mice. PMID- 1423850 TI - Absence of mutations in the functional parts of the p120-GAP gene in carcinogen induced mouse liver tumors. AB - The GTPase activating proteins (GAP) stimulate the intrinsic GTPase activity of ras-p21 thus converting the protein into its inactive form. We have now analyzed carcinogen-induced mouse liver tumors for the possible occurrence of mutational changes in one of the two known GAP genes, namely p120-GAP. RNA from a total of 21 tumors was reverse transcribed by use of GAP-specific primers, amplified by PCR and sequenced. All known functional domains of p120-GAP were included into the analysis. None of the liver tumors analyzed was found to be mutated within these regions of the gene. Moreover, Southern blot analysis of the gene did not reveal any structural changes. However, at five positions we discovered deviations from the published mouse fibroblast sequence, including two mouse strain-specific sequence polymorphisms. PMID- 1423851 TI - Tumour promoting phorbol esters activate phospholipase D in mouse skin. AB - Phospholipase D catalyses a transphosphatidylation reaction in the presence of primary alcohols, resulting in the formation of phosphatidylalcohol derivatives. In the present work we show that application of phorbol esters and butanol to mouse skin causes the rapid accumulation of phosphatidylbutanol (PBol), indicating the activation of phospholipase D. A similar accumulation of PBol was observed when the skin was treated with phorbol esters in vivo and skin pieces incubated with butanol in vitro. PBol formation was stimulated by the active tumour promoters 12-O-tetradecanoylphorbol-13-acetate (TPA), mezerein and phorbol 12,13-didecanoate (PDD) but not by the inactive promoter 4 alpha-PDD. Accumulation of PBol was not observed 24 h after application of TPA, a treatment which has been shown to deplete epidermal protein kinase C activity. PMID- 1423852 TI - Formation of 7-(4-oxobutyl)guanine in hepatic DNA of rats treated with N nitrosopyrrolidine. AB - We have reported previously the formation of two structurally distinct exocyclic guanine adducts (adducts 1 and 6) in liver DNA of F344 rats treated with N nitrosopyrrolidine (NPYR). In this study, we detected and characterized a previously unidentified guanine adduct in liver DNA of NPYR-treated rats. The structure of this adduct was established as 7-(4-oxobutyl)guanine (adduct 2) by comparison with the synthetic standard and confirmed by NaBH4 reduction to 7-(4 hydroxybutyl)guanine. The level of adduct 2 in liver DNA of F344 rats treated with 450 mg/kg of NPYR by i.p. administration was 643 +/- 9 mumol/mol guanine, approximately one-third of the level of adduct 1. This study is the first to demonstrate the in vivo formation of a formylalkyl-substituted guanine adduct by a nitrosamine. PMID- 1423853 TI - Cell-transforming potential of low-density lipoproteins. AB - Arterial smooth muscle cell proliferation is thought to be essential for the development of atherosclerotic lesions. The monoclonal hypothesis of atherogenesis proposes that the proliferative smooth muscle cells are derived from a stable transformed cell population. The present study demonstrates for the first time evidence that, in addition to carcinogens such as 3-methylcholanthrene (MCA), 'atherogenic' low-density lipoproteins (LDL) also possess cell transforming potential. LDL caused dose-dependent cytotoxicity and transformation of C3H/10T1/2 cells of type II and type III morphology of up to six transformed cell clones per 10(4) survivors in the concentration range of 50-200 micrograms cholesterol/ml after 72 h treatments. MCA (0.1 micrograms/ml) induced morphological transformation of 2.6 foci per 10(4) survivors. In a two-stage in vitro transformation assay LDL (5-25 micrograms cholesterol/ml) enhanced MCA induced cell transformation 2- to 2.4-fold in a dose-dependent way. 'Non atherogenic' high-density lipoproteins did not induce cell transformation by themselves or in an initiation-promotion model. These results show that LDL could act as (co)carcinogens. PMID- 1423854 TI - Search for Ha-ras codon 61 mutations in liver tumours caused by hexachlorobenzene and Aroclor 1254 in C57BL/10ScSn mice with iron overload. AB - C57BL/10ScSn mice administered iron--dextran and fed the environmental pollutants hexachlorobenzene (HCB) and polychlorinated biphenyls (PCBs) develop hepatic nodules and carcinomas within 18 months. A range of lesions from the livers were analysed for the presence of mutations in the Ha-ras proto-oncogene at codon 61 using the polymerase chain reaction to amplify DNA from formalin-fixed sections, followed by oligonucleotide hybridization. Only two mutations from 23 preneoplastic and neoplastic lesions induced by HCB were detected (a focus of altered cells and a trabecular cell carcinoma). With Aroclor 1254 no mutations were detected in 28 areas at various stages of carcinogenesis analysed. Sequencing of the two mutations generated by HCB showed a C-->T transversion at the first base of codon 61 (carcinoma) and an A-->T transversion at the second base (proliferative focus). Thus, in marked contrast to some other systems of mouse liver tumour induction, hepatocarcinogenesis caused by HCB and PCBs in C57BL/10ScSn mice is an example of carcinogenesis which does not involve a high frequency of Ha-ras gene mutation at codon 61. PMID- 1423855 TI - Inhibition of benzo[a]pyrene-induced tumorigenesis by myristicin, a volatile aroma constituent of parsley leaf oil. AB - Glutathione S-transferase (GST) assay-guided fractionation of parsley leaf oil from the edible plant Petroselinum sativum Hoffm. (Umbelliferae) led to the isolation of myristicin. Myristicin showed high activity as an inducer of the detoxifying enzyme GST in the liver and small intestinal mucosa of female A/J mice. Reduction of myristicin yielded dihydromyristicin that retained the GST inducing activity. Myristicin and dihydromyristicin were tested for their capacity to inhibit benzo[a]pyrene (B[a]P)-induced tumor formation in female A/J mice. A 65% inhibition of the tumor multiplicity in the lung was observed as the result of treatment of myristicin. Dihydromyristicin produced small or insignificant reduction of lung tumor formation. In the forestomach, myristicin showed a 31% inhibition of tumor formation; while dihydromyristicin exhibited a 27% inhibition. Comparison of the structures and activities indicated that the saturation of the isolated double bond in myristicin resulted in a significant decrease in the inhibitory activity against B[a]P-induced tumorigenesis. The present results showed that myristicin, an active inducer of GST activity, is an effective inhibitor of B[a]P-induced tumorigenesis in mice. Stimulation of GST activity by myristicin could be a major mechanism for its inhibition of B[a]P or other carcinogens that may be detoxified in the same manner. As a culinary herb parsley is regularly consumed by humans. Parsley leaf oil is also used extensively for garnishing and seasoning. The results of this study indicate that as a major volatile aroma constituent of parsley myristicin may be an effective cancer chemopreventive agent. PMID- 1423856 TI - Reversal of food restriction-induced inhibition of mouse skin tumor promotion by adrenalectomy. AB - Restricting the food intake of laboratory mice and rats markedly reduces the incidence of spontaneous and experimentally induced cancers. Using the two-stage skin tumorigenesis model in CD-1 mice, we report now that food restriction suppresses 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation of epidermal [3H]thymidine incorporation as well as TPA promotion of skin papillomas, whereas adrenalectomy completely reverses the inhibition in [3H]thymidine incorporation and tumor development. These results suggest that the adrenal gland may play an important role in mediating the tumor inhibitory effect of food restriction. PMID- 1423857 TI - Mechanisms of the enhanced liver carcinogenesis by choline in female rats: delay in liver growth after partial hepatectomy and stimulation of 2-AAF mitoinhibition. AB - Choline given to female rats resulted in an enhanced growth of focal lesions induced by the Solt-Farber model [diethylnitrosamine (DEN) as initiator and 2 acetylaminofluorene (2-AAF) associated with partial hepatectomy (PH) as promoter] when it was administered during promotion, but not during DEN treatment. Based on these data, the mechanisms by which choline might interfere with 2-AAF-PH promotion have been investigated. Compensatory liver growth after PH was faster in females than in males as shown by the restoration of both liver weight and protein content in rats fed a basal diet or a 2-AAF diet. The [3H]thymidine incorporation into DNA occurred a few hours earlier in females than in males. Choline administered to normal females delayed the peak of liver regeneration, by inhibiting [3H]thymidine incorporation into DNA and the mitotic index, resulting in later restoration of liver mass. 2-AAF feeding for 1 week markedly depressed the incorporation of precursor into DNA following PH in both sexes but at greater extent in males. Choline enhanced the mitoinhibition of 2-AAF only in females. No effect of choline was observed in male rats either with or without 2-AAF. The differential effect of choline between sexes in the development of focal lesions appeared to be related to the sexual dimorphism in the 2-AAF mitoinhibition and in the liver proliferation after PH. PMID- 1423859 TI - Peroxidative activation of o-phenylhydroquinone leads to the formation of DNA adducts in HL-60 cells. AB - Using 32P-postlabeling we studied DNA adduct formation in HL-60 cells treated with the o-phenylphenol metabolites o-phenylhydroquinone (o-PHQ) and o phenylbenzoquinone (o-PBQ). Treatment with 25-500 microM o-PHQ for 8 h produced one principal and three minor adducts with a relative distribution of 80, 10, 6 and 4%. The relative adduct levels from these treatments were 0.26-2.31 adducts/10(7) nucleotides. Treatment with 25-250 microM o-PBQ for 2 h resulted in a similar level of DNA modification and adduct distribution. Reaction of purified calf thymus DNA with o-PBQ produced one DNA adduct, which did not correspond to the major adduct produced in HL-60 cells. These results show that o-PHQ and o-PBQ can form DNA adducts. Peroxidase activation of o-phenylphenol may therefore play a role in the carcinogenic effect of this compound. PMID- 1423858 TI - Mammary carcinoma suppressor and susceptibility genes in the Wistar-Kyoto rat. AB - The Copenhagen (Cop) rat carries a homozygous mammary carcinoma suppressor (MCS) gene that prevents both spontaneous and induced mammary cancer. Here we identify an additional rat strain, the Wistar-Kyoto (WKy), that is resistant to the development of mammary carcinomas. This rat strain is similar to Cop in having one homozygous copy of a mammary suppressor gene. The Cop MCS gene and the gene responsible for mammary cancer resistance in the WKy were found to be very closely linked genetically and thus are likely to be the same gene. It was found that, unlike the Cop strain, the WKy strain also carries multiple copies of a susceptibility gene(s). This is analogous to the susceptible Wistar-Furth strain, which carries three copies of dominant susceptibility genes. The MCS gene is epistatic in regard to these susceptibility genes. The availability of the WKy rat strain carrying MCS on a background independent of the Cop strain will aid both mechanistic studies and the molecular cloning of MCS. PMID- 1423860 TI - High expression of manganese superoxide dismutase in 7,12 dimethylbenz[a]anthracene-induced ovarian cancer and increased serum levels in the tumor-bearing rats. AB - Manganese superoxide dismutase (Mn-SOD) is strongly expressed in human ovarian cancer, and the serum level of the enzyme is a useful marker for the diagnosis and monitoring of human ovarian cancer. In the present study we found that Mn-SOD was highly expressed in primary and transplanted ovarian cancers in rats induced by 7,12-dimethylbenz[a]anthracene (DMBA), as judged by enzyme-linked immunosorbent assay as well as by Northern blot analysis. The serum levels of Mn SOD in the tumor-bearing rats were also higher than those in control rats. The antibody strongly reacted with rat ovarian carcinoma tissues. These data suggest that DMBA-induced ovarian cancer in rats is a good experimental model for human ovarian cancer, and that Mn-SOD is also a good marker for disease in the animal model. PMID- 1423861 TI - 7-Methylguanine levels in DNA of smokers' and non-smokers' total white blood cells, granulocytes and lymphocytes. AB - The effect of smoking was investigated on the formation of 7-methylguanines in human peripheral white blood cells. DNA was isolated from total white blood cells, granulocytes and lymphocytes from 10 smokers and 10 non-smokers. 32P Postlabeling was performed by using anion-exchange chromatography enrichment of adducts. In smokers the mean DNA adduct levels were 6.9, 4.7 and 23.6 7 methylguanine residues/10(7) nucleotides in total white blood cells, granulocytes and lymphocytes respectively. The corresponding values in non-smokers were 3.4, 2.8 and 13.5 adducts/10(7) nucleotides. The mean adduct level was significantly higher in lymphocytes than in total white blood cells or granulocytes both in smokers and in non-smokers. The mean adduct levels differed significantly between smokers and non-smokers. PMID- 1423862 TI - A study of tobacco carcinogenesis XLVIII. Carcinogenicity of N' nitrosonornicotine in mink (Mustela vison). AB - During tobacco processing and smoking, nicotine and nornicotine give rise to N' nitrosonornicotine (NNN), a highly abundant, strong carcinogen. NNN is known to exert carcinogenic activity in mice, rats and hamsters. Major target organs for NNN carcinogenicity in the rat are the esophagus and the nasal mucosa, and in the Syrian golden hamster trachea and nasal mucosa. In comparison with the rat, the mink (Mustela vison) has a markedly expanded nasal mucosa. Therefore, we explored in this study whether the mink could serve as a non-rodent model for nasal carcinogenesis using NNN as the carcinogen. Twenty random-bred mink, beginning at the age of 3 weeks, received twice weekly s.c. injections of NNN, a total dose of 11.9 mM per animal over a 38 week period. All of the 19 mink at risk developed malignant tumors of both the respiratory and the olfactory region of the nose within 3.5 years. In most animals the malignant tumors, primarily esthesioneuroepithelioma, invaded the brain. Remarkably, NNN induced no other tumors in the mink. None of the control animals developed nasal tumors nor tumors at other sites during the 3.5 years of the assay. The historical data from the farm did not reveal any spontaneous occurrence of nasal tumors in mink at any age. This study supports the concept that NNN is a proven carcinogen for multiple species of mammals and that the mink can serve as a non-rodent, non-inbred animal model for nasal carcinogenesis, especially since NNN induces only tumors in the nasal cavity in this species and not at other sites, as it does in mice, rats and hamsters. PMID- 1423863 TI - Biliary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the rat. AB - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pancreas carcinogen in rats. The biliary excretion of NNK was therefore studied in anesthetized female Sprague-Dawley rats following i.p. administration of 0.7 mumol/kg [carbonyl-14C]NNK. The concentration of radioactivity peaked within 30 min and decreased thereafter exponentially. Cumulative excretion of radioactivity reached a plateau at 6-9% of the total dose. HPLC analysis revealed the presence of 4-hydroxy-4-(3-pyridyl)butyric acid (hydroxy acid), 4-oxo-4-(3-pyridyl)-butyric acid (keto acid), 4 (methylnitrosamino)-1-(3-pyridyl)-1-butyl beta-D-glucopyranosiduronic acid (NNAL Glu), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and NNK. NNAL Glu was the major metabolite contributing 34 +/- 4% of total radioactivity in bile at 30 min and 58 +/- 4% at 5 h. The percentage of acidic metabolites remained constant at approximately 20%. In contrast, the percentage of NNK and NNAL decreased within the first 2 h to < 5% and < 10% respectively. The elimination kinetics of NNK and its metabolites fitted into a one-compartment model with a half-life of 37 min for NNK, 52 min for NNAL and 110 min for NNAL Glu and acidic metabolites. In three rats dosed with 240 mumol/kg NNK i.p., the concentration of radioactivity peaked after 1-2 h and decreased very slowly thereafter. After 5-8 h a total of 12-17% of the dose has been excreted in the bile with no indication of a plateau. At all time points NNAL Glu was the major metabolite contributing up to 95% of total radioactivity in bile. The percentage of acidic metabolites was < 5% throughout the experiment. Whereas NNK contributed one-third of the radioactivity at 30 min and decreased rapidly, the percentage of NNAL in bile remained rather constant at approximately 5-10%. In conclusion, the detection of NNK, NNAL and NNAL Glu gives support to the hypothesis that tobacco-specific carcinogens could reach the pancreas retrograde from the bile, especially at high NNK concentrations. PMID- 1423864 TI - Repair of mitochondrial DNA after various types of DNA damage in Chinese hamster ovary cells. AB - Using methodology recently developed to assess gene-specific DNA repair, we have demonstrated that it is possible not only to study mitochondrial DNA repair, but also directly to compare mitochondrial and nuclear DNA repair in the same biological sample. Complex enzymatic mechanisms recognize and repair nuclear DNA damage, but it has long been thought that there was no DNA repair in mitochondria. Therefore, in an attempt to delineate more clearly which DNA repair mechanisms, if any, are functioning in mitochondria, we have investigated the repair of several specific DNA lesions in mitochondrial DNA. They include cyclobutane dimers, cisplatin intrastrand adducts, cisplatin interstrand crosslinks and alkali-labile sites. We find that pyrimidine dimers and complex alkylation damage are not repaired in mitochondrial DNA, and that there is minimal repair of cisplatin intrastrand crosslinks. In contrast, there is efficient repair of cisplatin interstrand crosslinks as evidenced by approximately 70% of the lesions being removed by 24 h. Additionally, there is efficient repair of N-methylpurines following exposure to methylnitrosourea with approximately 70% of the lesions being removed by 24 h. The results of these studies reveal that repair capacity of mitochondrial DNA damage depends upon the type of lesion produced by the damaging agent. We speculate that a process similar to the base excision mechanism for nuclear DNA exists for mitochondrial DNA but that there is no nucleotide excision repair mechanism to remove more bulky lesions in this organelle. PMID- 1423865 TI - Preferential and strand-specific DNA repair of (6-4) photoproducts detected by a photochemical method in the hamster DHFR gene. AB - A non-enzymatic method that was previously shown to create single-strand DNA breaks at the location of (6-4) photoproducts in the overall genome was adapted to measure (6-4) photoproducts at the level of the gene. This approach employs a photoisomerization step that converts the (6-4) photoproduct into the Dewar valence photoisomer, which is more alkaline labile and allows for the creation of a single-strand DNA break at this site. These strand breaks were quantified via Southern analysis and the DNA repair of (6-4) photoproducts was measured over 2, 4 and 8 h after a UV dose of 40 J/m2. A comparison of repair efficiency in the actively transcribed dihydrofolate reductase (DHFR) gene, a transcriptionally inactive genomic region and the overall genome (as measured by radioimmunoassay) showed preferential repair of the active gene. The active DHFR gene showed 59% repair by 8 h compared to 33% repair in the inactive downstream region. Analysis of (6-4) photoproduct repair in the transcribed and non-transcribed strands of the DHFR gene indicate some strand specificity with 62% repair in the transcribed strand at 8 h compared with 43% repair in the non-transcribed strand. However, this strand bias is much less distinct than has been reported for the major UV photoproduct, the cyclobutane pyrimidine dimer. PMID- 1423867 TI - Selective redistribution of protein kinase C isozymes by thapsigargin and staurosporine. AB - Protein kinase C (PKC) is the major cellular receptor for tumor promoting phorbol esters. Phorbol esters activate alpha-, beta-, delta- and epsilon-PKCs in GH4C1 rat pituitary cells and cause their redistribution from a soluble to a particulate fraction. We have now characterized the effect of several non-phorbol ester tumor promoters on PKC isozyme distribution in GH4C1 cells. The incomplete tumor promoter mezerein caused redistribution of alpha-, beta-, delta- and epsilon-PKCs. Thus, it did not display partial agonist activity. The phosphatase inhibitor okadaic acid did not cause redistribution of any isozyme. The calcium ATPase inhibitor thapsigargin and the ser/thr kinase inhibitor staurosporine caused redistribution of epsilon-PKC and, to a lesser extent, delta-PKC. Although the mechanism of the selective effect on delta- and epsilon-PKCs is not yet known, these data clearly demonstrate that their subcellular distribution can be regulated by a pathway that does not influence alpha- and beta-PKCs. Phorbol ester activation of epsilon-PKC was associated with appearance of a more slowly migrating immunoreactive band in the particulate fraction. Both epsilon-PKC forms accumulated phosphate during phorbol ester treatment. The phosphorylated forms of epsilon-PKC were preferentially recovered in the particulate fraction. Although staurosporine caused redistribution, it prevented the phorbol dibutyrate (PDBu) mediated appearance of the upper band of the doublet and the increased phosphorylation of both bands. The PDBu-mediated redistribution of alpha- and beta-PKCs was not inhibited by staurosporine, even though staurosporine effectively inhibited PKC catalytic activity. Therefore, catalytic activity is not required for redistribution. PMID- 1423866 TI - Overexpression of human DNA repair protein N-methylpurine-DNA glycosylase results in the increased removal of N-methylpurines in DNA without a concomitant increase in resistance to alkylating agents in Chinese hamster ovary cells. AB - N-Alkylpurines induced in DNA by simple monofunctional alkylating agents are known to be cytotoxic and possibly indirectly mutagenic. These adducts are removed by the ubiquitous N-methylpurine-DNA glycosylase (MPG) in a multistep repair pathway. Chinese hamster ovary (CHO) cell clones expressing 2- to 16-fold enhanced levels of MPG activity were isolated from cells stably transfected with human MPG cDNA expression plasmids. The in vivo removal of 3-methyladenine and 7 methylguanine from some of these lines was analyzed and was observed to reflect their MPG levels. These cell lines did not develop increased resistance, as compared to the control, in regards to cytotoxic, mutagenic and sister chromatid exchange inducing effects of the alkylating agents that induce 3-alkyladenine and 7-alkylguanine as the major alkyl adducts in DNA. These results suggest that the MPG activity is not limiting in the multi-step repair pathway of N-alkylpurines in CHO cells. PMID- 1423869 TI - 32P-postlabeling analysis of the formation and persistence of DNA adducts in mammary glands of parous and nulliparous mice treated with benzo[a]pyrene. AB - The susceptibility of the rodent mammary gland to known chemical carcinogens can vary with the stage of gland development. Full-term pregnancy (parity) can confer permanent structural and functional changes in the gland that are associated with decreased breast cancer risk in humans and protection from mammary carcinogenesis in rodents. In this study, the formation and persistence of benzo[a]pyrene (B[a]P)-derived DNA adducts in vivo was determined in the abdominal mammary organs of adult nulliparous and parous BALB/c mice treated orally with the carcinogen. Mammary DNA isolated from animals in both groups revealed only one major adduct on TLC maps by P1-nuclease 32P-postlabeling analysis. The major adduct co-migrated with the (+)-enantiomer of anti-BPDE-dGp. Much lower levels of the (-)-enantiomer were detected. Most of the adduct quantitated was probably contributed by cells of the stromal compartment, since the gland-free organ (cleared fat pad) generated essentially equivalent profiles and level of adduct by 32P-postlabeling. Comparable levels of the B[a]P-derived adduct were observed in the intact mammary organ of both nulliparous and parous mice during a time course from 1 to 28 days after treatment. In both cases, adduct removal occurred exponentially with a half-life of approximately 16 days. The capacity for de novo formation of reactive metabolites by the mammary organ was demonstrated in vitro: digests of DNA from mammary mince exposed to B[a]P generated an adduct on TLC maps that also co-migrated with the (+)-anti-BPDE-dGp standard. Thus, our cumulative findings confirm the capacity of mammary cells to form potentially carcinogenic DNA adducts; however, the functional changes that occur in the mouse mammary gland as a result of parity did not influence the profile, level or persistence of adduct following exposure to a known carcinogen. Other factors, such as changes in mammary cell cycle kinetics or responsiveness to promotional stimuli may be more causally related to reduction in incidence of neoplasia observed in parous animals. PMID- 1423868 TI - Formation of 8-hydroxydeoxyguanosine within DNA of mouse keratinocytes exposed in culture to UVB and H2O2. AB - Exposure to UV light contributes to the development of skin cancer. The importance of reactive oxygen species in UV-radiation carcinogenesis has been recognized for some time and several associated DNA base modifications have been identified. In particular, 8-hydroxydeoxyguanosine (8-OHdG) has been well studied as an indicator of oxidative damage to calf thymus DNA exposed to a variety of oxygen-generating systems, including UV light. However, to date, few studies of 8 OHdG have been conducted in cell or animal systems and those in vitro investigations that studied UV exposure have used UVC (< 290 nm), not the UVB (290-320 nm) or UVA (320-400 nm) ranges to which organisms are exposed through sunlight. The objective of this study was to measure 8-OHdG formation in the DNA of cultured mouse keratinocytes exposed to UVB. Using HPLC with electrochemical detection, background levels of 8-OHdG were approximately 6 fmol/micrograms DNA in DNA isolated and digested to the nucleoside level. UVB induced 8-OHdG up to 100% above that for mock-treated cells at a dose of 630 mJ/cm2 (dose-response range: 210-630 mJ/cm2). UVB exposure at 630 mJ/cm2 combined with 5 mM H2O2 elevated 8-OHdG formation up to 280% above that in control cells, whereas H2O2 alone had no effect. These results suggest that factors which increase the generation of reactive oxygen species by UV light may be potent cofactors of UV radiation carcinogenesis. PMID- 1423870 TI - Purification and characterization of rat hepatic microsomal N,O-acyltransferases. AB - Hepatic microsomes of female F344 rats were capable of N,O-acyltransfer of N hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) and N-hydroxy-N-formyl-2 aminofluorene (N-OH-FAF), N-deacetylation of N-OH-AAF and N-acetyl-2 aminofluorene (2-AAF), and O-deacetylation of 4-nitrophenyl acetate (NPA). The activity for N,O-acyltransfer of N-OH-FAF was approximately 20 times greater than that of N-OH-AAF. These microsomal activities were inducible by phenobarbital and were inhibitible by paraoxon. Four distinct N,O-acyltransferases were purified from solubilized hepatic microsomes of phenobarbital pretreated rats. These enzymes were purified to homogeneity, as judged by SDS-PAGE and analytical IEF. Their pIs were approximately 5.0, 5.5, 6.0 and 6.5 and their mol. wts were approximately 60, 61, 180 (a homotrimer of 59 kDa) and 60 kDa respectively. All the enzymes catalyzed the N,O-acyltransfer of N-OH-FAF, the N-deacetylation of N OH-AAF and 2-AAF and the O-deacetylation of NPA. Among these four enzymes, the hydrolysis of NPA was best catalyzed by pI 6.5 protein, of 2-AAF by the pI 5.5 protein, and of N-OH-AAF by the pI 5.0 protein. The pI 5.5 and pI 6.5 proteins were equally active for N,O-acyltransferase and were more active than the other enzymes. The present study demonstrates that rat hepatic microsomal activities of N,O-acyltransfer, N-deacetylation and O-deacetylation are attributable to the same enzymes. PMID- 1423871 TI - Transformation of non-tumorigenic osteoblast-like human osteosarcoma cells by hexavalent chromates: alteration of morphology, induction of anchorage independence and proteolytic function. AB - Soluble chromium (VI) compounds either alone or in combination with 3 methylcholanthrene (MC) were used to transform non-tumorigenic osteoblast-like human osteosarcoma cells (HOS TE85). The Cr(VI) compounds were highly toxic to these cells with LC50 values in the range of approximately 0.5-1.0 microM. Continuous passaging of the treated cells resulted in sustained increase in anchorage-independent (AI) colony formation. Treatment with Cr(VI) and MC resulted in substantial increase in AI growth. At the XVth passage, a number of individual AI colonies were expanded in culture and used for further studies. The cells are refractory in appearance and grow as 'nests' rather than as monolayers. The cell lines have relatively high plating efficiency (PE) in soft agar and respond to promotional effect of phorbol-12-myristate-13-acetate by an increase in PE and in the size and number of AI colonies. While the isolated cells are not tumorigenic when tested in athymic nude mice, most of the lines possess higher levels of plasminogen activator (PA) activity, considered as one of the markers of transformation. This is also reflected in the increase in the steady state level of urokinase type PA mRNA. These results show that Cr(VI) compounds are capable of promoting human cells to an altered phenotype characteristic of a stage in the carcinogenesis cascade. PMID- 1423872 TI - Aflatoxin toxicity in cultured human epidermal cells: stimulation by 2,3,7,8 tetrachlorodibenzo-p-dioxin. AB - Aflatoxin B1 (AFB1) at 1 microgram/ml was markedly toxic to human epidermal cells grown in the Rheinwald-Green 3T3 feeder layer system. At 0.1 microgram/ml, the toxicity was barely evident, as assessed by colony expansion during a 2 week exposure, but it was dramatically stimulated by 5 nM 2,3,7,8-tetrachlorodibenzo-p dioxin (TCDD), which was non-toxic alone. Neither AFB1-dihydrodiol nor AFB2 were toxic in the presence or absence of TCDD, indicating that metabolism to the 8,9 epoxide was responsible for the AFB1 toxicity. Stimulation of AFB1 epoxidation by TCDD was also indicated by the > 20-fold increase in DNA adduct formation in cultures exposed to [14C]AFB1 and TCDD for 4 days as compared to AFB1 alone. Analysis of free metabolites in culture medium by reverse-phase HPLC revealed that confluent epidermal cultures metabolized AFB1 to AFM1, AFB2a and aflatoxicol. In the presence of TCDD, the levels of AFM1 were higher (14 versus 3% of dose) as were those of AFB2a (3 versus 0.5% of dose), while aflatoxicol levels were lower (0.8 versus 2% of dose). In the absence of irradiated 3T3, the toxicities of AFB1, AFB2, AFM1 and aflatoxicol to cells in serum-free medium (0.15 mM Ca2+) were similar to those in the feeder layer system. Although this moderately low calcium concentration appeared quite satisfactory for observing toxicity, the response was attenuated at a lower calcium concentration (0.09 mM Ca2+). PMID- 1423875 TI - Mutational specificity of chromium(VI) compounds in the hprt locus of Chinese hamster ovary-K1 cells. AB - Chromium(VI) compounds exert their genotoxicity and mutagenicity by complex metabolic reducing pathways that generate a variety of reactive forms of chromium and free radicals. To investigate the molecular nature of chromium-induced mutations, we characterized the entire coding region of the hypoxanthine (guanine) phosphoribosyltransferase (hprt) gene of 27 independent mutants derived from chromium(VI) oxide (CrO3)-treated Chinese hamster ovary-K1 cells, by direct sequencing of PCR-amplified cDNA. Among these mutants, 10 consisted of single base substitutions, five contained two base substitutions, one had four base substitutions, six were splicing mutations, and five exhibited single base pair insertions or deletions. All of the base substitutions and most of the frameshift mutations observed were located at A/T-rich sequences. More than 90% of the base substitutions (22/24) occurred in A.T base pairs. Among them, T-->A and T-->G transversions (18/22) predominated. The mutational hotspots for single and double base substitutions were the 3' thymidine of 5'PuT and thymidines of 5'ATTT sequences respectively. This mutational specificity was also observed in CHO-K1 cells treated with two other chromium(VI) compounds, namely K2Cr2O7 and PbCrO4. Strand bias was noticed in chromium mutagenicity, since 77% of T base substitutions occurred on the non-transcribed strand. This highly sequence specific mutation spectrum suggests that a particular form of chromium may directly interact with DNA at these hotspot sequences. PMID- 1423873 TI - Cigarette smoking related polycyclic aromatic hydrocarbon-DNA adducts in peripheral mononuclear cells. AB - Studies on cigarette smoking related polycyclic aromatic hydrocarbon-DNA adducts in blood have produced conflicting results. To determine whether a subset of specific white blood cells is a useful marker for monitoring exposure to cigarette smoke, blood was obtained from 63 heavy smokers and 27 non-smokers. Adduct levels were determined by competitive enzyme-linked immunosorbent assay with a polyclonal antiserum recognizing benzo[a]pyrene and structurally related diolepoxide-DNA adducts. Analysis of the lymphocyte plus monocyte fraction from smokers indicated 70% had detectable adducts with a mean of 4.38 +/- 4.29 adducts/10(8) nucleotides, while in non-smokers the corresponding values were 22% and 1.35 +/- 0.78/10(8) (P < 0.001). Plasma cotinine levels differed significantly in smokers (286 +/- 90 micrograms/l) compared to non-smokers (4.4 +/- 3.3 micrograms/l) (P < 0.001). However, cotinine was not correlated with self reported smoking history in these heavy smokers. Nor were DNA adducts in smokers correlated with cigarettes per day, pack-years and plasma cotinine, indicating large interindividual variation in DNA adduct formation. These data demonstrate lymphocytes plus monocytes from smokers have elevated levels of polycyclic aromatic hydrocarbon diolepoxide-DNA adduct levels compared to non-smokers. PMID- 1423874 TI - Promoting effects of both dietary cholesterol and cholestyramine on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters. AB - The effects of dietary cholesterol and cholestyramine on pancreatic carcinogenesis initiated with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated in 120 female Syrian golden hamsters. BOP (70 mg/kg body weight) was injected s.c. once at the beginning of the experiment. Starting 2 weeks later, the animals were then maintained on basal diet or diets containing either 0.5% cholesterol or 1% cholestyramine for a further 16 weeks. All surviving hamsters were killed at week 18, and the pancreas tissues examined histologically. The incidences of pancreatic carcinomas in hamsters fed cholesterol and the cholestyramine supplement were 40.0 and 30.0% respectively; in both cases significantly higher than the 6.9% incidence in the basal diet group. Cholesterol contents of the serum, pancreas and liver were significantly increased by cholesterol feeding and significantly decreased by the cholestyramine diet. The cholesterol diet also significantly increased pancreatic protein and DNA contents, and the concentration of total bile acids and the level of lithocholic acid in gallbladder bile. The cholestyramine diet significantly increased total pancreatic DNA and protein contents, and pancreatic weight. The results thus indicated that both dietary cholesterol and cholestyramine can enhance BOP initiated pancreatic carcinogenesis in hamsters. PMID- 1423877 TI - Molecular dynamics of alkylated DNA. AB - The effect of methylation of the O4 atom of thymine in two oligonucleotide sequences is investigated by molecular dynamics simulations. Three types of environments are considered including: (i) in vacuo calculation, with a distance dependent dielectric function and unhydrated counter-ions; (ii) in vacuo calculation, with a distance-dependent dielectric constant and hydrated counter ions; and (iii) with a 9 A thick explicit water layer and counter-ions. In all environments, the oligonucleotide sequence containing the chemically modified thymine paired with guanine is more stable than the oligonucleotide sequence in which the modified thymine is paired with adenine. The methyl group attached to the O4 atom of thymine is found in a syn configuration with respect to the N3 atom. The best fit between the experimental NMR results and the molecular dynamics simulations is obtained using the environment with hydrated counter ions. PMID- 1423876 TI - Response of the ke test to NCI/NTP-screened chemicals. III. Complementary value of ke in screening for carcinogens. AB - The value of using a physico-chemical carcinogen-screening test, the ke test, in conjunction with the Salmonella typhimurium/microsome assay (the Ames test) and/or structural alerts of reactivity (the S/A test), is analyzed on the basis of the response of the three tests to 171 chemicals of known rodent carcinogenicity. The Ames test is widely used to screen chemicals for potential carcinogenicity; however, its relatively low sensitivity (proportion of true positives among carcinogens tested) has prompted a search for complementary tests that increase sensitivity without an unacceptable decrease in specificity (proportion of true negatives among non-carcinogens tested). The S/A test is a structural analysis based on recognition of chemicals groups likely to react with DNA. The S/A test does not complement the Ames test well, because of the high similarity of responses (dependence) between these two tests. The ke test measures the affinity of a test chemical for electrons, and has a sensitivity and specificity comparable to the Ames test. The ke test is shown in this work to complement both the Ames test and the S/A test. Addition of the ke test to either the Ames test or the S/A test results in a substantial decrease in false negatives and an approximately equal increase in false positives, which is a trade-off that would be desirable in all but the least risk averse situations. The S/A and ke battery has a sensitivity of > 0.9, and could be applied to untested chemicals without any biological testing. In view of these observations, it is proposed that the ke test be considered in developing future strategies to optimize the screening of potential carcinogens in the most cost-effective manner. PMID- 1423878 TI - Inhibition of mouse skin tumorigenesis by dexamethasone occurs through a Ha-ras independent mechanism. AB - The Ha-ras oncogene has been shown to be point-mutated and overexpressed in papillomas induced by the two-stage skin tumorigenesis regimen of 7,12 dimethylbenz[a]anthracene (DMBA) and promotion with 12-O-tetradecanoylphorbol-13 acetate (TPA). Glucocorticoids inhibit mouse skin tumorigenesis when applied with the initiation agent or with the promoting agent. We have extended these studies to evaluate whether dexamethasone (Dex) treatment could inhibit development of already established tumors. An additional objective of this study was to investigate whether glucocorticoids directly inhibit Ha-ras gene expression at the level of transcription during skin tumorigenesis. In this report we demonstrate that topical Dex treatments significantly suppressed the formation of additional tumors relative to the acetone control group. However, Northern blot analysis of total RNA isolated from representative tumors during a series of sequential weeks of promotion indicated that Dex did not have a direct effect on Ha-ras steady-state mRNA levels despite the decrease in additional tumor numbers in the Dex-treated groups. We also investigated short-term effects of Dex on endogenous Ha-ras expression in normal mouse epidermis. Topical Dex administration had no effect on endogenous Ha-ras steady-state mRNA levels in normal skin after 2 or 24 h. To ensure that endogenous corticosterone levels in the SENCAR mouse were not influencing our results, Ha-ras mRNA levels in epidermis from SENCAR mice adrenalectomized 48 h prior to being killed were compared to Ha-ras levels in normal epidermis by Northern blot analysis. The data from this analysis revealed that bilateral adrenalectomy had no effect on Ha-ras steady-state mRNA levels in epidermis compared to ras levels in normal mouse epidermis. In summary, our results demonstrate that although Dex can inhibit further tumor development in DMBA/TPA-treated mouse epidermis, it does not do so by directly effecting Ha-ras gene expression in mouse epidermis. PMID- 1423879 TI - Evidence for a ras gene mutation in azoxymethane-induced colonic aberrant crypts in Sprague-Dawley rats: earliest recognizable precursor lesions of experimental colon cancer. AB - The main objective of the present investigation was to understand the molecular events involved in the genesis of aberrant crypt foci. Aberrant crypt foci were induced in Sprague-Dawley rats with a single injection of azoxymethane. Aberrant crypts have been identified topographically in the colon and are hypothesized to represent preneoplastic lesions. In order to understand the molecular events involved in the early stages of colon cancer, PCR-amplified DNA from aberrant crypts was hybridized with oligonucleotide probes specific for the detection of point mutations in codon 12 of K-ras. The mutation identified was a G to A transition resulting in the substitution of the amino acid aspartic acid (asp) for glycine (gly). This mutation was present in 6/19 (32%) of aberrant crypts examined. The identical mutation was also identified in adenomacarcinoma tissue while no mutation could be detected in normal intestinal mucosa. For further confirmation of these results, the presence of the mutated ras protein (rasAsp 12) was detected in aberrant crypts by immunohistochemistry. This investigation provides the first identification of a ras point mutation in aberrant crypt foci. PMID- 1423881 TI - Reaction kinetics of DNA-histone crosslinking by vinyl acetate and acetaldehyde. AB - The formation and stability of DNA-protein crosslinks (DPXLs) formed by incubation of pUC13 plasmid DNA and calf thymus histones with 1-100 mM acetaldehyde was studied using a filter binding assay. DPXLs were formed at a rate of 127 DPXLs/plasmid molecule/mmol acetaldehyde in a reaction containing 1 microgram of histones and 0.33 microgram of DNA at 37 degrees C for 1 h. Acetaldehyde-induced DPXLs were unstable at 37 degrees C, with loss of up to 75% by 8 h. Crosslink formation was significantly higher at lower pH, with 3- and 2 fold higher levels at pH 5 and 6 respectively than at pH 7.5. Induction of DPXL formation by 1-100 mM vinyl acetate in the presence of rat liver microsomes was observed at 37 degrees C over 3 h. DPXL accumulation followed S-phase enzymatic kinetics, with a rate of formation of 1.1 DPXLs/plasmid molecule/mmol vinyl acetate/microgram microsomal protein/microgram DNA. Vinyl acetate was unable to cause formation of DPXLs in the absence of microsomes. A carboxylesterase inhibitor, bis-(p-nitrophenyl) phosphate, was able to block DPXL formation by vinyl acetate and microsomes. This work supports the hypothesis that DPXL formation by vinyl acetate requires microsomal metabolism to acetaldehyde, which is the active crosslinking agent. PMID- 1423880 TI - Mechanism of formation of the thioether conjugate of the bladder carcinogen 2 amino-4-(5-nitro-2-furyl)-thiazole (ANFT). AB - The formation of thioether conjugates is an important pathway for inactivation of certain carcinogens. This study assessed the mechanism by which the bladder carcinogen 2-amino-4-(5-nitro-2-furyl)-thiazole (ANFT) forms a glutathione conjugate (ANFT-SG). Peroxidatic metabolism of ANFT, in the presence of glutathione, results in ANFT-SG formation. Both prostaglandin H synthase and horseradish peroxidase can catalyze this reaction. Metabolism of the reducing co substrates ANFT, phenol, and aminopyrine elicit increases in oxidized glutathione (GSSG). ANFT-SG formation is potentiated by phenol and aminopyrine. tert Nitrosobutane (tNB), a thiyl radical trap, prevented increases in both GSSG and ANFT-SG. Increasing concentrations of ANFT elicited corresponding increases in both GSSG and ANFT-SG. Peroxidatic metabolism of ANFT in the presence of glutathione, but not in the absence of glutathione, resulted in oxygen uptake. The formation of GSSG and oxygen uptake are consistent with the presence of thiyl radicals during ANFT metabolism. 5,5-Dimethyl-1-pyrroline N-oxide, a thiyl radical trap, was not as effective as tNB in inhibiting the formation of ANFT-SG and GSSG. Ascorbic acid, a reducing cosubstrate and antioxidant, was very effective in preventing ANFT-SG and GSSG formation, while the strong nucleophile methionine was ineffective. To clarify effects of different test agents, their effects on aminopyrine cation radical formation were assessed. Results are consistent with ANFT reacting with thiyl radicals to form ANFT-SG. ANFT appears to be a thiyl radical trap. Peroxidatic metabolism of ANFT probably results in the formation of a cation radical rather than a carbon-centered radical. PMID- 1423882 TI - Accumulation of O6- and 7-methylguanine in DNA of N-nitroso-N-methylbenzylamine treated rats is restricted to non-target organs for N-nitroso-N-methylbenzylamine induced carcinogenesis. AB - The distribution and accumulation of O6-methylguanine (O6-meGua) and 7 methylguanine (7-meGua) was investigated immunocytochemically in target and non target tissues of rats injected twice weekly with 0.5 mg N-nitroso-N methylbenzylamine (NMBzA)/kg for 16.5 weeks. Seventy two hours after every two or three doses, two NMBzA-treated rats and one control rat were killed. Tissue specific cell proliferation was investigated after two injections of bromodeoxyuridine (BrdU) to rats unexposed to NMBzA. Neither O6-meGua- nor 7 meGua-specific immunostaining could be observed in the target tissues for tumor induction, i.e. esophagus, tongue and forestomach. Accumulation of both O6-meGua and 7-meGua was found, however, in nasal, tracheal and bronchiolar epithelia and glands--tissues for which tumor induction by NMBzA has not been reported. An explanation for this phenomenon might be the relatively low levels of cellular proliferation we observed in the latter epithelia. The present results support the hypothesis that the tumorigenic organotropism of NMBzA is determined both by the level of DNA methylation and the proliferative capacity of the methylated cells. PMID- 1423883 TI - Characterization of ethanol's enhancement of tumorigenesis by N nitrosodimethylamine in mice. AB - The concentration-, time- and route-dependent effects of ethanol co administration on tumorigenesis by N-nitrosodimethylamine (NDMA) were characterized in strain A male mice. With drinking-water administration, 1% ethanol was as effective as 5 or 10% in effecting a 4-fold enhancement of lung tumorigenesis by 5 p.p.m. NDMA. In a study of cumulative effects over time, 10% ethanol given with 1 p.p.m. NDMA resulted in a progressive increase in lung tumors from 16 to 72 weeks. In addition, at 72 weeks, the ethanol co-treatment resulted in a significant increase in kidney adenomas and possibly in vascular tumors of liver. A single i.g. dose of 5 mg/kg NDMA was significantly tumorigenic for lung, and the effect was dose-dependently increased by inclusion of ethanol, for up to a 9-fold enhancement with 20% ethanol. When 10% ethanol was given in the drinking water while NDMA was administered as 20 1 mg/kg doses by other routes--i.g., i.p., s.c. or i.v.--the ethanol treatment was without effect on lung tumor numbers. Collectively, the results provide strong support for inhibition of hepatic first-pass clearance of NDMA by cytochrome P450 2E1 as the mechanism of ethanol's effect, and suggest that several other possible mechanisms are unlikely. They also illustrate that a moderate dose of ethanol cumulatively increases tumor risk from a low dose of NDMA given over most of the lifetime of the animal. PMID- 1423884 TI - Proliferative dependent regulation of the glyceraldehyde-3-phosphate dehydrogenase/uracil DNA glycosylase gene in human cells. AB - The relationship between the proliferative dependent expression of the glyceraldehyde-3-phosphate dehydrogenase (GAPDH)/uracil DNA glycosylase (UDG) gene and the induction of uracil DNA glycosylase activity was examined in human cells. Three different cell types were studied to determine whether the growth dependent regulation of this multifunctional gene was a common characteristic of human cells. These included WI-38 normal embryonic lung fibroblasts, a Japanese Bloom's syndrome non-transformed skin fibroblast cell strain (GM-05289) and a lymphoblastoid cell line transformed by the Epstein-Barr virus. The Japanese Bloom's syndrome cells displayed the altered immunoreactivity with marker monoclonal antibody 40.10.09 which characterizes cells from this human genetic disorder. In noncycling human cells Northern blot analysis using a plasmid (pChug 20.1) which contained the human GAPDH/UDG cDNA revealed a single 1.6 kb transcript. In each case, the expression of this gene was increased during cell proliferation. This increase in GAPDH/UDG gene expression was identical to that observed for UDG enzyme activity. Further, using anti-human UDG monoclonal antibodies, there was a growth-dependent rise in immunoreactivity suggesting an increase in the level of antigenic protein. These results demonstrate that: (i) the expression of the GAPDH/UDG gene was dependent on the proliferative state of the cell; and (ii) a correlation existed between the transcription of this gene and the level of uracil DNA glycosylase enzyme activity. PMID- 1423885 TI - Lack of correlation between DNA methylation and hepatocarcinogenesis in rats and hamsters treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. AB - Previous studies have demonstrated that the tobacco-specific nitrosamine 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induced liver tumors in F344 rats but not in Syrian golden hamsters. The aim of this study was to determine whether there was a correlation between the persistence of O6-methylguanine (O6 mGua) adducts and the rate of recovery of O6-methylguanine-DNA methyltransferase (O6-mGuaT) after depletion in the liver and susceptibility to NNK in F344 rat and Syrian golden hamster injected s.c. with NNK (80 mg/kg). The levels of both 7 methylguanine and O6-mGua reached a maximum 24 h after NNK treatment. O6-mGua in NNK-treated rat liver was undetectable after 48 h. In the rat, the depletion of O6-mGuaT activity occurred within 4 h following NNK treatment. A subsequent rapid recovery of enzyme activity was observed 36 h after NNK exposure. In contrast, high levels of O6-mGua persisted in hamster liver DNA and no O6-mGuaT activity was detected up to 336 h after NNK injection. Thus, the persistence of O6-mGua in hamster liver is most likely related to a lack of recovery of the O6-mGuaT. These results suggested that factors other than O6-mGua may be determining NNK-induced hepatocarcinogenesis in rats. An aldehyde generated by alpha-hydroxylation of NNK, 4-oxo-4-(3-pyridyl)butanal, inhibited O6-mGuaT activity in rat hepatocytes, suggesting that this aldehyde contributes to the carcinogenicity of NNK by inhibiting this repair enzyme. PMID- 1423887 TI - Activity of diverse tumor promoters in a keratinocyte co-culture model of initiated epidermis. AB - The suppression of focal growth of initiated mouse keratinocytes by co-culture with normal keratinocytes can be overcome by treatment of co-cultures with the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). This keratinocyte co-culture model was developed as an analog of initiated mouse epidermis to facilitate the study of tumor promotion in cell culture. A number of promoters of TPA-type [those with protein kinase C (PKC) as receptor] were compared to non-TPA-type promoters for activity in the keratinocyte co-culture model. The TPA-type promoters teleocidin and aplysiatoxin show comparable activity to that of TPA. Exposure of co-cultures to oleoyl-2-acetylglycerol, a diacylglycerol activator of PKC, also induces focal outgrowth of initiated cells, suggesting that PKC is likely to be involved in the mechanism of action of these compounds. However, the involvement of alternative pathways (not involving PKC directly) for clonal selection are evident since the non-TPA-type promoters okadaic acid, staurosporine and thapsigargin are also active in the assay. Thus, the keratinocyte co-culture model differs from fibroblast models of normal and neoplastic co-cultures in which only TPA-type promoters are active. In further contrast to certain fibroblast co-cultures, TPA does not inhibit cell-cell communication under conditions that suppress focus formation. Taken together with previous data, we conclude that the keratinocyte co-culture model may have broad application for detecting skin tumor promoters, and may be useful for dissecting the mechanism by which normal epidermal cells suppress the growth of initiated cells. PMID- 1423886 TI - Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco specific carcinogen, by rabbit nasal microsomes and cytochrome P450s NMa and NMb. AB - Rabbit nasal olfactory and respiratory microsomes were found to catalyze the alpha-hydroxylation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) with specific activities of 262 and 136 pmol/min/mg protein in the formation of keto aldehyde, and of 318 and 190 pmol/min/mg protein in the formation of keto alcohol respectively. The formation of NNK-N-oxide was observed in experiments with rabbit olfactory and respiratory microsomes, but not with rat nasal microsomes. However, the rat nasal microsomes had higher activity in catalyzing the alpha hydroxylation of NNK. In a reconstituted system, rabbit P450NMa, a major constitutive P450 isozyme in nasal microsomes, displayed high activities in the formation of the keto aldehyde and the keto alcohol with apparent Km values of 15 and 9 microM respectively. In comparison, rabbit olfactory specific P450NMb had a low activity in catalyzing the formation of keto aldehyde (Km = 186 microM) and no activity in the formation of keto alcohol. The P450NMa-catalyzed oxidation of NNK was inhibited by nicotine and diallyl sulfide. Kinetic studies indicated that nicotine is a competitive inhibitor. These results demonstrate that enzymes in rabbit nasal microsomes, especially P450NMa, efficiently catalyze the bioactivation of NNK. PMID- 1423888 TI - DNA adduct dosimetry and DNA repair in rats and pigs given repeated doses of procarbazine under conditions of carcinogenicity and human cancer chemotherapy respectively. AB - Procarbazine (PCZ), an antineoplastic agent that produces methylated bases in DNA after metabolic activation, has been implicated in the development of secondary cancers in patients treated for a primary neoplasm. The repair of the important promutagenic lesion, O6-methylguanine (O6-meG) by O6-alkylguanine-DNA alkyl transferase (AGT) is believed to be crucial for the stability of O6-meG and for the tumorigenic outcome after exposure to methylating carcinogens. Using two different animal models, we investigated methyl DNA adduct dosimetry and DNA repair in (i) female rats given repeated doses of PCZ for 20 weeks under conditions of carcinogenicity, and (ii) female pigs administered repeated doses of PCZ for 4 weeks according to a regimen comparable to that given to human subjects undergoing cancer chemotherapy. After each successive week, four rats and three pigs were killed and tissues including blood, liver, mammary gland, spleen, thymus and lymph node were taken. The levels of O6-meG, 7-methylguanine (7-meG) in DNA and of AGT were determined in these tissues. In the rat, O6-meG in the liver DNA, and to a lesser degree in the spleen was efficiently removed throughout the 20 week dosing period, as indicated by the O6-meG/7-meG ratio being much less than 0.11. In the target organs, accumulation of O6-meG began in the mammary gland after 9 weeks, and in the lymph node and thymus after 3 weeks of dosing. Interestingly, the accumulation of O6-meG in the mammary gland correlates well with a concomitant decrease in AGT level as from week 10 and may be related to the induction of mammary gland tumors, first detected in two animals at week 10. In pigs, after a total dose of 750-4000 mg of PCZ, the range of 7-meG detected in leukocyte DNA was 21-66 mumol/mol G, which compares well with recent findings in cancer patients treated with PCZ. Similar levels of 7-meG were detected in the pig liver, thymus and lymph node. O6-MeG was only detectable in leukocyte DNA at week 4 with our present method. Compared with control pig tissues, a depressed AGT level was found in the leukocyte, lymph node and brain of the treated animals. PMID- 1423890 TI - Expression of cytochrome P450 in yeast after different chemical treatments. AB - In Saccharomyces cerevisiae a number of chemical agents induce synthesis of cytochrome P450. A cytochrome P450 gene has been well characterized in this yeast: CYP51, which codes for a constitutive enzyme involved in the 14 alpha demethylation of lanosterol, a key step in the biosynthesis of ergosterol. In this work, we have analysed the level of transcription of the CYP51 gene in correlation with cytochrome P450 enzymatic activity after treatment with several chemical agents known to interact with cytochrome P450. Using as a probe a DNA fragment whose identity to the CYP51 gene was established by sequence analysis and mapping on chromosome VIII, a unique RNA species was observed in all treatment samples. The increased level found for this transcript in cells treated with ethanol, 20% glucose, phenobarbital or 5-methoxypsoralen correlates with the levels of induction in cytochrome P450 enzymatic activity measured in cells grown under the same conditions, indicating that induction of cytochrome P450 by these treatments is regulated at the transcriptional level. PMID- 1423889 TI - The influence of ventral UVA exposure on subsequent tumorigenesis in mice by UVA or UVB irradiation. AB - Exposure to ultraviolet-B radiation (UVB: 280-315 nm) can result in a decreased immune response. This immune suppression can be restricted to the exposed skin site (local immune suppression) but may also be systemic. To investigate whether ultraviolet-A radiation (UVA: 315-400 nm) could also exert such a systemic effect, we performed the present investigation. The study consisted of two parts. Experiment I: 24 albino hairless mice (SKH:HRI) were ventrally exposed to UVA radiation for 300 days (glass-filtered Philips TLK09 fluorescent tubes, daily dose: 350 kJ/m2), while 24 control mice were left unexposed. After this period the control animals were still tumour free, but 60% of the exposed animals had developed abdominal tumours. Subsequently ventral exposures were stopped and both groups were dorsally exposed to identical UVB regimens (Westinghouse FS40, daily dose: 900 J/m2). Experiment II: this was virtually the same as experiment I, but here the mice were dorsally exposed to UVA radiation (glass-filtered Philips TLK09, daily dose: 290 kJ/m2) instead of UVB radiation. If we look at all tumours induced dorsally, we find no significant influence of pre-exposures to UVA radiation. This holds for dorsal UVB as well as for dorsal UVA exposures. In contrast to UVB, however, the UVA radiation induced many papillomas. Excluding the papillomas from the analysis we find that the induction of non-papillomas (mainly squamous cell carcinomas) under dorsal UVA exposure, is slightly enhanced in the ventrally pre-exposed group (difference significant at the P < 0.05 level). This suggests that UVA radiation induced only a weak systemic effect. Ventral UVA pre-exposure did not appear to affect dorsal skin irritation as expressed by scratch marks. The induction period for hyperkeratosis, however, was significantly shortened by the ventral UVA pre-exposure; this applied to dorsal UVB as well as dorsal UVA exposures. PMID- 1423891 TI - Inhibitory effects of curcumin on tumor initiation by benzo[a]pyrene and 7,12 dimethylbenz[a]anthracene. AB - The effects of topical administration of curcumin on the formation of benzo[a]pyrene (B[a]P)-DNA adducts and the tumorigenic activities of B[a]P and 7,12-dimethylbenz[a]anthracene (DMBA) in epidermis were evaluated in female CD-1 mice. Topical application of 3 or 10 mumol curcumin 5 min prior to the application of 20 nmol [3H]B[a]P inhibited the formation of [3H]B[a]P-DNA adducts in epidermis by 39 or 61% respectively. In a two-stage skin tumorigenesis model, topical application of 20 nmol B[a]P to the backs of mice once weekly for 10 weeks followed a week later by promotion with 15 nmol 12-O-tetradecanoylphorbol 13-acetate (TPA) twice weekly for 21 weeks resulted in the formation of 7.1 skin tumors per mouse, and 100% of the mice had tumors. In a parallel group of mice, in which the animals were treated with 3 or 10 mumol curcumin 5 min prior to each application of B[a]P, the number of tumors per mouse was decreased by 58 or 62% respectively. The percentage of tumor-bearing mice was decreased by 18-25%. In an additional study, topical application of 3 or 10 mumol curcumin 5 min prior to each application of 2 nmol DMBA once weekly for 10 weeks followed a week later by promotion with 15 nmol TPA twice weekly for 15 weeks decreased the number of tumors per mouse by 37 or 41% respectively. PMID- 1423892 TI - Chemoprevention of smoke-related DNA adduct formation in rat lung and heart. AB - The formation of smoke-related DNA adducts and their chemoprevention were investigated in tissues of male Sprague-Dawley rats, by testing a total of 132 DNA samples by synchronous fluorescence spectrophotometry (SFS), which mainly detects benzo[a]pyrene diolepoxide (BPDE)-DNA adducts. Groups of six animals each were exposed whole-body to mainstream cigarette smoke, once daily, for up to 40 consecutive days. No adduct was revealed in liver DNA, whereas smoke-related DNA adducts were detectable in the lung from the 8th day of exposure and continued to increase until the 40th day. Adducts to heart DNA, which were monitored after 28 and 40 days of exposure, attained even higher levels than those detected in the lungs of the same animals. A high correlation existed between the amounts of smoke-related DNA adducts measured in these two organs. The daily administration by gavage of the thiol N-acetyl-L-cysteine (NAC), an effective mutation and cancer chemopreventive agent, which had been previously shown to inhibit the formation of SFS-positive DNA adducts in rats receiving intratracheal instillations of benzo[a]pyrene, significantly prevented occurrence of the same adducts in both heart and lungs of smoke-exposed rats. No fluorescence signal was observed in liver, lung, or heart DNA of sham-exposed animals. The findings of this molecular dosimetry study complement the results of parallel histopathologic, cytogenetic, biochemical and metabolic analyses of tissues and cells from the same rats, providing evidence for a variety of significant alterations produced by exposure to cigarette smoke and for the specific protective role of NAC. PMID- 1423893 TI - Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange frequency in the lymphocytes of patients with multiple myeloma undergoing cytostatic therapy with melphalan and prednisone. AB - An investigation was made of 17 patients with multiple myeloma using the method of alkaline filter elution for the detection of DNA damage and the determination of sister chromatid exchange (SCE) frequency in peripheral lymphocytes during a course of chemotherapy with melphalan and prednisone. We were able to detect elevated SCE frequencies in pretreated patients that approximately doubled during the therapeutic cycle. An appreciable level of DNA cross-linking was detected by alkaline filter elution; DNA cross-linking scarcely increased during a course of chemotherapy. The increase in the SCE frequency during the first therapy cycle was even greater in the case of patients with newly diagnosed multiple myelomas. The results obtained by alkaline filter elution and measuring SCE frequencies suggest that these techniques are suitable as methods in molecular epidemiology, especially if applied to persons who are chronically exposed to cytostatic drugs. Whether or not the methods could be valuable in evaluating therapy response needs further investigation. PMID- 1423895 TI - Plant peroxisomes: recent studies on function and biosynthesis. PMID- 1423894 TI - Role of peroxisomes in mammalian metabolism. PMID- 1423896 TI - Biogenesis of peroxisomes in mammals. PMID- 1423898 TI - Peroxisome biogenesis and function in Hansenula polymorpha. PMID- 1423897 TI - A genetic approach to the biogenesis of peroxisomes in the yeast Saccharomyces cerevisiae. PMID- 1423899 TI - Transcriptional regulation of genes encoding proteins involved in biogenesis of peroxisomes in Saccharomyces cerevisiae. PMID- 1423900 TI - Targeting signals for protein import into peroxisomes. PMID- 1423901 TI - Peroxisomal disorders in man. PMID- 1423902 TI - Modifications of adhesion properties and proteoglycan structure in rat embryo fibroblast cultures with increasing passages. AB - Adhesion properties of rat embryo fibroblast cultures and proteoglycans (PGs) produced both in the growth medium and in the cell layer were investigated with increasing passages. Both cell-cell and cell-substrate adhesion increased with increasing subculture number. Cell adhesion properties were improved by cell treatment with chondroitinase ABC. The increase in subculture number was coupled with a constant increase of PG molecular size, which was particularly evident in cell layer extracts. The ratio HS-PGs/DS-PGs increased with increasing passages. PG modifications are likely to represent evidence of changes in extracellular matrix organization and could play a role in the increase of cell adhesion properties. PMID- 1423903 TI - Treatment of childhood encopresis--a review. AB - Children with encopresis may present to a number of different professionals. The literature on different treatment methods is reviewed. The roles of verbal psychotherapy, physical treatment, behaviour therapy and mixed treatment programmes are discussed. PMID- 1423904 TI - Child development: what do parents expect? AB - Expectations of future development were assessed in parents of non-disabled children (n = 240) using the Predictive Adaptive Ability Questionnaire (PAAQ). The reliability estimate for the overall PAAQ was 0.90, with a test-retest reliability of 0.99 and an interrater reliability of 0.83. Parental expectations did not significantly differ from normal adaptive ability developmental standards. Longitudinal examination of parental expectations and their influence on child development and the impact of chronic illness on such expectations is recommended. PMID- 1423907 TI - Sleep clinics with health visitors: a 2-year evaluation. AB - This study was undertaken to evaluate a service for sleep clinics over a time span of 2 years. The service was operated jointly by health visitors and clinical psychologists and based on a previous model run by the same team of psychologists and child development advisors. The outcome was not supportive of this type of service in terms of referral rates over a period of time, improvement rate, continued existence or cost-effectiveness of such a service. The reasons for the difficulties of such clinics are discussed. PMID- 1423905 TI - Training of head control in the sitting and semi-prone positions. AB - The purpose of this study was to compare the semi-prone (SP) and sitting (SIT) training positions with respect to head control in children with cerebral palsy, before and after 5 weeks biofeedback training using a head position trainer (HPT). Four children were randomly assigned to each of two training groups: (a) SP on a prone board inclined 45 degrees above the horizontal and (b) SIT in their personal wheelchair and orthotic device. The HPT, secured to the child's head, controlled a video-cassette player, turning it off when the head deviated beyond 25 degrees from the vertical (termed an error). The time in error and the number of errors during test periods of 3 minutes, without feedback and completed in both the SP and the SIT positions, were determined immediately before and after, and at 16 weeks after training. The SIT trained group performed significantly better immediately post-training in three of four comparisons (P < 0.01), but the groups performed similarly in the other eight comparisons--four immediately pre training and four at 16 weeks post-training (P > 0.05). Post-training scores for the total group (n = 8) were significantly improved over pre-training scores, regardless of the test position or the criterion measurement (P < 0.05). Biofeedback training with a HPT can be effective in either the SIT or the SP positions, with improvement lasting at least 16 weeks after training is discontinued. PMID- 1423908 TI - Endotoxin stimulates interleukin-6 production by human Kupffer cells. AB - Interleukin-6 (IL-6) induces acute-phase protein synthesis in human hepatocytes. We evaluated whether the contiguous hepatic macrophages, human Kupffer cells (HKC), produce IL-6 in response to an inflammatory stimulus. HKC were harvested from collagenase-digested normal liver biopsies and purified (greater than 95% by phagocytosis) by adherence. Following overnight culture, 5 x 10(5) HKC were repleted with fresh media with or without 2.5 micrograms/ml of endotoxin (LPS). Parallel cultures contained polymyxin-B (10 micrograms/ml) or antihuman-IL-6 antibody (4 units/ml). Timed supernatants were collected and IL-6 levels (ng/ml) measured (B9.9 proliferative bioassay). Data analysis was by the paired Student's t test. Unstimulated HKC produced negligible IL-6 levels (less than 0.150 ng/ml). Endotoxin invoked early and sustained HKC production of IL-6, which was completely (P less than 0.001) abrogated by the addition of the anti-IL-6 antibody. Polymyxin B, an LPS-inhibitor, also blocked (P less than 0.001) IL-6 production, indicating the specificity of the response to the inflammatory stimulus. This is the first evidence that HKC can produce IL-6 in response to LPS. Local intrahepatic production of IL-6 may provide a necessary paracrine signal for HKC to amplify directly neighboring hepatocyte acute-phase responses during inflammation in man. PMID- 1423906 TI - Portage guide to early intervention: cross-cultural aspects and intra-cultural variability. AB - The issues arising from implementing an early intervention service, developed in the rural United States in the late 1960s in a range of different cultural contexts over a period of a quarter of a century, are explained. Services from India, Bangladesh, Jamaica and the United Kingdom are compared. As well as considering cross-cultural aspects of Portage, variability within one country, the United Kingdom, is considered by comparing one service in an inner-city area and one in a rural area. PMID- 1423909 TI - Effect of positive end-expiratory pressure on pulmonary vascular pressure-flow characteristics in canine endotoxin shock. AB - The vascular pulmonary pressure-flow (P-Q degree) relationships were studied in anesthetized dogs in order to characterize the distribution of total resistance in the pulmonary bed with respect to incremental resistance and critical closure prior to and after endotoxin insult. Incremental resistance was computed as the slope of the P-Q degree relation, whereas critical closure was referred to as the extrapolated pressure intercept at zero flow. P-Q degree coordinates were obtained by varying Q degree through graded inflation of right atrial balloon. The gradients across the arterial segment (Pa = Ppa - Pc) and across the venous segment (Pv = Pc - Pw) of the pulmonary vasculature were defined by the computation of effective capillary pressure (Pc) obtained from the analysis of the transient decay of pulmonary artery pressure (Ppa) toward wedge pressure (Pw) after arterial occlusion. Six group E dogs were infused with endotoxin at a rate of 0.25 microgram/kg min, while six additional animals served as control (group C). Endotoxin induced increases in flow resistance from 0.056 to 0.096 mm Hg/ml/min/kg due to arterial vasoconstriction and increases in critical closure from 2.3 to 8.4 mm Hg due to a venous waterfall. Before and after endotoxin insult, we assessed effects of each of three levels of static lung inflation (PEEP) on P-Q degree relationships.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423910 TI - Hepatic insulin resistance during chronic hyperdynamic sepsis. AB - Disturbances in normal glucose metabolism and homeostasis which manifest as hyperglycemia and glucose intolerance are often observed during clinical sepsis. Skeletal and myocardial muscle as well as whole body insulin resistance have been demonstrated in this laboratory and others during experimental and clinical sepsis. The existence of hepatic insulin resistance in sepsis has yet to be fully elucidated. This study was undertaken to assess hepatic insulin resistance during chronic hyperdynamic sepsis. Animals were randomly assigned to a septic (n = 7), sham (n = 7), or control (n = 7) group. Sepsis was induced in anesthetized dogs via a midline laparotomy whereby a fecal-soaked gauze sponge was placed amid the intestines. Sham animals underwent a laparotomy with mechanical manipulation of the intestines but no fecal implant. Control animals had no previous surgery. Sham and control dogs were pair-fed with the septic dogs. On postoperative day 7, after an overnight fast, animals were anesthetized, intubated, and ventilated. Via a left subcostal laparotomy, electromagnetic flow probes were placed to measure hepatic arterial and portal venous blood flows. Cannulae were placed in femoral, portal, and hepatic veins and femoral artery and used to calculate hepatic outputs of glucose, lactate, and oxygen during a basal period and hyperinsulinemic-euglycemic clamps which used intravenous insulin infusions which ranged from 0.4 to 4,000 mU/min. Mean arterial blood pressure decreased with increasing insulin concentrations in septic animals while no change was seen in control or sham animals. In control and sham animals, net hepatic glucose output (NHGO) decreased in response to increasing insulin levels. Septic animals showed no such inverse relationship and, moreover, showed no change in glucose output response to any insulin infusion, i.e., hepatic insulin unresponsiveness during sepsis. Net hepatic lactate output during basal pre-insulin period during sepsis was negative. This was in contrast to the positive outputs in control and sham animals. Glucose infusion rates (GIR) increased during insulin infusion but were not different between groups at any insulin infusion rate. These data demonstrated a hepatic insulin resistance (unresponsiveness) during chronic hyperdynamic, hypermetabolic sepsis. PMID- 1423911 TI - Role of extracellular Ca2+ in ischemia-reperfusion injury in the isolated perfused rat liver. AB - The influx of extracellular Ca2+ has been postulated to be one of the mediators of ischemia-reperfusion injury. A possible link between Ca2+ influx and oxygen radical generation has also been suggested. In the present study, using the isolated perfused rat liver, we evaluated the role of extracellular Ca2+ on oxygen radical generation, liver damage, and lipid peroxidation during 30 min ischemia and 60 min of reperfusion. Oxygen radical generation in the liver was continuously monitored by lucigenin-enhanced chemiluminescence. Liver damage and lipid peroxidation were evaluated by measuring lactate dehydrogenase (LDH) and thiobarbituric acid reactive substances (TBARS) release into the effusate, respectively. In the absence of extracellular Ca2+ (much less than 30 microM) oxygen radical generation from the liver increased gradually over 2 hr and there were concomitant increases in LDH and TBARS release. When livers were made ischemic and then reperfused, oxygen radical generation increased at the onset of reperfusion and then decreased over 30 min of reperfusion. After 30 min of reperfusion, livers reperfused with low Ca2+ buffer showed a linear increase in oxygen radical generation as well as progressive increases in LDH and TBARS release. On the other hand, livers reperfused with Ca2+ containing (1.25 mM) buffer showed no further increase in oxygen radical generation and no evidence of progressive liver damage and lipid peroxidation. These results suggest that Ca2+ overload is not a primary cause of liver ischemia-reperfusion injury and that the presence of extracellular Ca2+ during reperfusion is necessary to maintain normal liver function. PMID- 1423912 TI - Acute hemodynamic effects of hypertonic (7.5%) saline infusion in patients with cardiogenic shock due to right ventricular infarction. AB - The hemodynamic effects, after infusion of 4 ml/kg of hypertonic (7.5%) saline solution (HS), were evaluated in six patients (mean age = 56.6 years) with cardiogenic shock (CS) due to right ventricular infarction (RVI). Basal condition data (mean +/- SEM) were as follows: cardiac index (CI) = 1.9 +/- 0.1 1/min/m2, arterial pressure (AP) = 66.5 +/- 0.9 mmHg, and systemic vascular resistance (SVR) = 31.3 +/- 1.0 mmHg/1/min/m2. Five- and 240-minute post-HS infusion data (respectively) revealed: CI = 3.3 +/- 0.1* and 2.9 +/- 0.1* 1/min/m2, AP = 87.7 +/- 1.6* and 80.7 +/- 2.2* mmHg, and SVR = 22.5 +/- 0.6* and 24.5 +/- 1.1* mmHg/1/min/m2 (*P less than 0.05 compared to baseline values). These data suggest that small-volume infusion of HS induced an important acute and sustained hemodynamic improvement in these patients with CS due to RVI. PMID- 1423914 TI - Continuous measurement of lactate concentration in skeletal muscle and liver interstitium using a microdialysis method after acute hemorrhage in anesthetized rats. AB - Interstitial lactate concentration in rat skeletal muscle was continuously measured using a microdialysis method following an acute hemorrhage. For comparison, similar measurements were also performed for liver. Normal lactate levels of skeletal muscle and liver interstitium were 0.58 +/- 0.10 mM and 1.23 +/- 0.04 mM, respectively. After withdrawal of 30% of the estimated total blood volume within 3 min, a constant high blood lactate level was achieved. The lactate concentrations in muscle and liver interstitium also increased to 270 and 210% of the basal levels, respectively, but they did not exceed the blood level. These findings led us to hypothesize that skeletal muscle as well as liver functions as a lactate consumer rather than a producer after acute hemorrhage. PMID- 1423913 TI - Low dose calcium administration increases mortality during septic peritonitis in rats. AB - Calcium is essential for normal cellular function. However, increases in cell calcium are also involved in cellular dysfunction and death by activating destructive enzymatic processes such as proteases, nucleases, and lipases. Since ionized hypocalcemia is common during sepsis, calcium is often administered in an attempt to normalize circulating levels. Previous studies using endotoxin and large amounts of calcium demonstrated increased mortality in calcium-treated animals. This study extends these preliminary data to endogenous sepsis (cecal ligation) and low dose calcium therapy. Sprague Dawley rats (n = 9 per group) had jugular catheters placed and their cecums ligated. They were randomized to an infusion of D5W at 1 ml/hr, calcium chloride at 4 mg/ml/hr (Low Ca), or calcium chloride at 6 mg/ml/hr (High Ca) for 24 hr. An additional group of animals received calcium chloride at 6 mg/ml/hr but had no surgery. Animals were followed for 24 hr survival. A separate group of animals (n = 6 per group) was prepared in a similar manner. Blood was obtained 6 hr following cecal ligation for circulating endotoxin concentrations, and animals were sacrificed. Calcium infusion increased ionized calcium levels slightly (low Ca, 1.12 +/- .06 to 1.21 +/- .09; high Ca, 1.06 +/- .04 to 1.16 +/- .05; P less than 0.05). Survival (24 hr) was 100% in the nonseptic controls and D5W septic animals, 67% in the low Ca septic group, and 44% (P less than 0.05) in the high Ca septic group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423915 TI - Passive immunization with antibodies against tumor necrosis factor (TNF-alpha) protects from the lethality of splanchnic artery occlusion shock. AB - Splanchnic artery occlusion shock was induced in anesthetized rats by clamping splanchnic arteries for 45 min. Survival rate, serum and macrophage tumor necrosis factor (TNF-alpha), peritoneal macrophage phagocytosis, and killing activities were evaluated. Shocked rats died within 2 hr, whilst all sham-shocked rats survived more than 6 hr. Serum and macrophage TNF-alpha was undetectable in sham-shocked rats while shocked rats exhibited increased serum (110 +/- 5 U/ml 90 min after release of occlusion) and macrophage levels (122 +/- 4.5 U/ml 90 min after release of occlusion) of TNF-alpha. Furthermore, splanchnic artery occlusion shock produced cardiovascular changes, reduced macrophage phagocytosis (23 +/- 4.6%) and killing (6 +/- 1.1%) activities, and induced a massive necrosis of the ileum. A passive immunization with a hyperimmune serum containing antibodies against murine TNF-alpha significantly protected rats from the lethal effects of splanchnic artery occlusion shock, lowered serum TNF-alpha (6 +/- 2.1 U/ml), and completely reverted the impairment in peritoneal macrophage phagocytosis (48 +/- 4.8%) and killing (13 +/- 1.5%) activities. In addition passive immunization had beneficial effects on the cardiovascular changes occurring during splanchnic artery occlusion shock and prevented necrosis of the ileum induced by this model of shock. By contrast, pretreatment with polymyxin B, an "antiendotoxin" antibiotic, did not modify the lethal effects and the TNF alpha production induced by splanchnic artery occlusion shock. Furthermore, endotoxin was undetectable in the blood of splanchnic artery occlusion shocked rats. These findings are consistent with the involvement of TNF-alpha in splanchnic artery occlusion shock and suggest that the cytokine represents an important mediator of non-septic shock. PMID- 1423916 TI - Kupffer cell exacerbation of hepatocyte hypoxia/reoxygenation injury. AB - In order to examine the possible contribution of the Kupffer cell to the generation of hypoxia/reoxygenation injury in the liver, primary cultures of hepatocytes, either alone or in coculture with Kupffer cells, were exposed to 90 min of sublethal hypoxia followed by 120 min of reoxygenation. Prolonged incubation of cocultured hepatocytes and Kupffer cells resulted in increased release of lactic dehydrogenase (LDH) indicating cell injury even under normoxic conditions. LDH release was further increased by the presence of Kupffer cells during hypoxia/reoxygenation. To determine whether or not this effect of Kupffer cells might be the result of oxygen-derived free radical production, we assessed the efficacy of the enzymatic scavengers superoxide dismutase (SOD) + catalase in ameliorating the Kupffer cell mediated injury. SOD + catalase was effective in preventing free radical injury generated by hypoxanthine + xanthine oxidase. However, SOD + catalase did not ameliorate hepatocyte injury caused by Kupffer cells. Thus, activation of Kupffer cells may be an important factor in the genesis of liver injury, but the mediator of Kupffer cell exacerbation of hepatocyte injury appears to be a mechanism other than free radicals released into the medium. These results indicate that chemical substances from the activated Kupffer cells may cause hepatocyte damage, which cannot be blocked by SOD + catalase, and suggest that these substances at reflow may be important for the genesis of reperfusion injury in vivo. PMID- 1423917 TI - Cardiovascular effects of thyrotropin-releasing hormone in normotensive and hypotensive rats: role of rostral ventrolateral medulla. AB - To ascertain the central mechanism of the effects of thyrotropin-releasing hormone (TRH) on the cardiovascular system, we evaluated the effects of this neuropeptide on unit fires in the rostral ventro-lateral medulla (RVL), mean arterial pressure (MAP), and heart rate (HR) in normotensive and hypotensive rats. Intracerebroventricular injection (i.c.v.) of 10 micrograms TRH significantly increased MAP and HR in both normotensive and hypotensive rats. No similar effects were observed after saline injection. If electrolytic lesions of bilateral RVL were made, the cardiovascular effects of TRH i.c.v. failed to occur. TRH i.c.v. markedly increased the firing frequency of most units in the RVL. In particular, TRH i.c.v. increased the firing frequency of most units excitatory to a fall in MAP and decreased the firing frequency of most units inhibitory to a fall in MAP in normotensive rats. Moreover, a drop of MAP as low as 40 mmHg for 10 min resulted in an increase of the firing frequency of most units. The effect of TRH i.c.v. on the RVL units in the hypotensive rats was similar to that in the normotensive rats. Our findings suggest that TRH is able to intensify the cardiovascular activities and the RVL plays a key role in the effects of TRH on the cardiovascular system in both normotensive and hypotensive rats. PMID- 1423918 TI - Increase in renal magnesium overflow following aortotomy-induced hemorrhage in pigs. AB - Hemorrhage causes an increase in plasma Mg++ levels. This article identifies some of the tissues contributing to the hemorrhage induced increase in plasma Mg++. Anesthetized, splenectomized pigs were subjected to a 5 mm aortotomy. Blood samples from the abdominal aorta, inferior vena cava, pulmonary artery, hepatic portal vein, and renal vein were sampled for Mg++ changes caused by this uncontrolled hemorrhage. Aortotomy produced a rapid drop in arterial pressure and cardiac output, both of which remained depressed for the following 120 minutes (P less than 0.05). By 120 minutes, 6 of the 8 pigs survived, but three of the six survivors showed signs of cardiovascular decompensation. A significant increase in arterial plasma Mg++ was indicated by a paired t-test (P less than 0.05). Analysis of the venous samples also revealed a significant increase during the post-aortotomy period. Renal venous and hepatic portal venous plasmas both showed increases greater than that in the arterial plasma. The renal and splanchnic tissues, then, were partly responsible for the increase in the arterial Mg++ which follows hemorrhage. PMID- 1423919 TI - The cardiovascular effects of gamma-hydroxybutyrate following hemorrhage. AB - We have previously shown that gamma-hydroxybutyrate (GHB) protects the small intestine against ischemia/reperfusion injury. This study examined the effects of GHB on cardiovascular function and intestinal microcirculation following hemorrhage. Hypotension was induced in control group of hamsters by controlled hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Following 60 minutes of hypovolemia the shed blood was returned. This procedure resulted in complete intestinal mucosal microvascular stasis 2 hours following the return of shed blood. A second group of animals was treated with GHB (600 mg/kg body weight) and, despite the loss of 37% of total blood volume, GHB treatment completely prevented the microcirculatory stasis, following the reinfusion of shed blood. In male Wistar rats treated with GHB (200 mg/kg) after the induction of hemorrhage, blood pressure rapidly increased to pre-hemorrhage levels following treatment, even though the shed blood was not returned. Cardiac output (CO) also increased to pre-hemorrhage levels. Sodium chloride solution, in the same molar concentration as GHB (23% NaCl), produced much smaller, but statistically significant, increases in MAP and CO. In animals given an equal volume of normal saline, a gradual increase in MAP was observed, reaching statistical significance at 75 minutes following treatment. Three hours following hemorrhage, serum levels of creatine kinase were 3-fold higher, whereas aspartate aminotransaminase and alanine aminotransferase levels were 2-fold higher in both normal saline and hypertonic saline-treated animals than in GHB-treated animals. These experiments suggest that GHB can prevent ischemic complications following a hypovolemic episode and may improve survival following severe hemorrhage. PMID- 1423920 TI - Favourable effect of defibrotide in lipid A-induced shock in pigs. AB - Defibrotide (DEF), a compound previously found to stimulate vascular prostacyclin (PGI2) formation, has been investigated in an experimental model of septic shock. Anesthetized pigs were subjected to i.v. infusion of lipid A (1.5 mg/kg per hr for 4 hr). DEF (50 mg/kg per hr) or vehicle were infused i.v. throughout the experiments, starting 1 hr prior to lipid A. Two out of 7 pigs receiving vehicle survived lipid A infusion for 4 hr, whereas 6 out of 7 DEF treated animals survived this period (P less than 0.05). DEF delayed the shock-induced depression of platelet count and preserved platelet secretory function (collagen-induced ATP secretion). DEF increased plasma PGI2 by 45% (P less than 0.05) during lipid A infusion and tended to reduce thromboxane levels. DEF did not change eicosanoid formation in sham-shock pigs (n = 4 per group). In vivo treatment with DEF significantly increased the stimulatory effect of bradykinin (1 microM) and arachidonic acid (100 microM) on PGI2 formation ex vivo of mesenteric and iliac artery segments. The improvement of survival in lipid A-induced shock by DEF may be related to an enhancement of vascular PGI2 generation, potentially due to a reduction of shock-induced platelet activation and microcirculatory dysfunction. PMID- 1423922 TI - Production of tumor necrosis factor-alpha and interleukin-6 in mice infected with group B streptococci. AB - Group B streptococci (GBS) are a leading cause of sepsis and meningitis in neonates. Since cytokines are thought to play an important role in septic shock, we have studied serum levels of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in BALB/c mice infected with type III GBS. TNF alpha and IL 6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial serum samples obtained after infection. After i.p. challenge with an LD50, serum TNF alpha rose above baseline values as early as 3 hr, peaked at 7 hr, and returned to baseline values at 20 hr. IL-6 serum levels rose concomitantly with TNF alpha, peaking 8 hr after challenge. No serum TNF alpha activity was detected in the course of sublethal infections. However, a transient rise in TNF alpha levels was observed after i.v. inoculation of high numbers (greater than or equal to 1 x 10(8) of heat-killed GBS. When groups of mice were injected i.v. with a single dose of anti-TNF alpha rabbit serum 2 hr before challenge with an LD90 or LD30, no effect was noted in terms of survival, although the serum TNF alpha peak was completely abrogated. Serum TNF alpha does not seem to play an obligatory role in GBS-induced lethality of adult mice. However, further studies are needed to assess better the role of this cytokine in the pathogenesis of GBS sepsis. PMID- 1423921 TI - Protective effect of platelet-activating factor antagonist on hepatic energy metabolism following transient hepatic inflow occlusion in rabbits. AB - To investigate whether or not platelet-activating factor (PAF) is a mediator of the liver injury resulting from transient hepatic inflow occlusion (Pringle's maneuver), the effect of pretreatment with a potent PAF antagonist (CV6209) on hepatic energy metabolism was evaluated following 30 min of inflow occlusion in rabbits. At 60 min after declamping, the arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate), reflecting hepatic mitochondrial redox state (NAD+/NADH), increased to 1.10 +/- 0.05 (mean +/- SEM) in the CV6209 (5 mg/kg) pretreated group (group 1, n = 5) compared with 0.72 +/- 0.06 (P less than 0.01) in the untreated group (group 2, n = 5). Hepatic energy charge at 60 min after declamping was significantly higher in group 1 than in group 2 (0.871 +/- 0.010 vs. 0.800 +/- 0.023; P less than 0.05). Pretreatment with CV6209 had no significant influence on these parameters in sham-operated animals. The present study demonstrates that pretreatment with CV6209 has a protective effect against the impairment of hepatic energy metabolism following transient hepatic inflow occlusion. PMID- 1423923 TI - Circulating cytokines: the tip of the iceberg? AB - Circulating cytokines, particularly TNF alpha, IL-1, IL-6 and IL-8, can be detected during severe infections consecutively to an exacerbate release by activated cells. The presence or absence of cytokines within biological fluids reflects a rather complex balance between enhancing and inhibitory signals acting on producer cells, between production and catabolism, and between their binding to the target cells and the modulation of their receptors on the cell surface. Furthermore, their presence does not necessarily parallel their activity and a possible interplay between the cytokines and their corresponding inhibitors should be considered. On the contrary, the absence of detectable circulating cytokines does not indicate an absence of production by activated cells. We discuss the concept that circulating cytokines represent the tip of the iceberg. PMID- 1423924 TI - Efficacy of monoclonal antibody against tumor necrosis factor alpha in an endotoxemic baboon model. AB - Tumor necrosis factor alpha (TNF) has been described as a primary mediator of the pathophysiology associated with bacterial sepsis/endotoxemia. We tested the efficacy and possible mechanisms of protection of a monoclonal antibody against TNF (TNF Mab) in a low mortality (29%), endotoxemic baboon model. A number of parameters were monitored at days 0, 1, 2 and 5-7 after challenge with 2 mg E. coli endotoxin/kg. TNF Mab pretreatment (15 mg/kg) prevented the increase in detectable serum TNF and the early perturbations in cardiovascular function which occurred in the control group. Early metabolic dysfunction was delayed in the TNF MAb group and was attenuated thereafter. Dysfunction of the kidney, liver, and coagulation systems and the increased IL-6 levels were significantly attenuated in the TNF MAb group; neutrophil activation was not affected by TNF MAb. No deaths occurred in the TNF MAb group. These results support the hypothesis that TNF plays a central role in the pathophysiology of endotoxic shock. PMID- 1423925 TI - Polymyxin-B suppresses endotoxin-induced insulin hypersecretion in pancreatic islets. AB - Endotoxin induces insulin hypersecretion in vivo, which results in hyperinsulinemia and glucose dyshomeostasis. Polymyxin-B (PMX-B), an inhibitor of protein kinase C (PKC), has been shown to ameliorate the consequences of endotoxin-induced hyperinsulinemia in vivo. To explore the mechanism for this effect in vitro, this study determined whether PMX-B could alter endotoxin induced insulin hypersecretion in isolated pancreatic islets of Langerhans. Pancreases were obtained from fasted, male, Sprague-Dawley rats treated with either saline (control) or endotoxin (S. enteritidis B, 16.7 mg/kg, i.v.). Three hours after the experimental treatment, islets were isolated by collagenase digestion and then incubated for 1 hr in Krebs Ringer bicarbonate buffer containing 0.5% bovine albumin, 10 mM HEPES, 300 mg/dl D-glucose, phorbol 12 myristate 13-acetate (PMA, 1 microM when present), and PMX-B (1 or 10 mM when present). In the absence of PMA and PMX-B, "endotoxic" islets hypersecreted immunoreactive insulin (IRI) relative to control islets. PMA, the prototypical PKC activator, significantly increased IRI secretion from both control and "endotoxic" islets. The additional inclusion of PMX-B (1 mM or 10 mM) in the incubation media significantly reduced insulin secretion from both control and "endotoxic" islets and suppressed the insulin hypersecretion observed in "endotoxic" islets. Since insulin secretion occurs at least partially through mechanisms dependent on PKC activation, the ability of PMX-B to suppress insulin hypersecretion in "endotoxic" islets suggests that activation of PKC within pancreatic beta-cells may play a role in the excess insulin secretion and hyperinsulinemia associated with endotoxicosis. PMID- 1423926 TI - Regulation of glucose metabolism by free fatty acid availability in septic and nonseptic rats. AB - An inhibitory effect of fatty acid oxidation on glucose uptake and oxidation has been demonstrated in heart and skeletal muscle under certain experimental conditions. This reciprocal relationship has been termed the glucose-fatty acid cycle. The purpose of the present study was to determine under in vivo conditions whether this interaction was operational in various nonmuscle tissues, and whether infection altered the activity of this cycle. Oral administration of alpha-methylpalmoxirate (MPA; 75 mg/kg), a known inhibitor of long-chain fatty acid oxidation, suppressed hepatic glucose production by 54% and increased whole body glucose disappearance by 15% in nonseptic rats. In contrast, MPA produced a larger reduction of glucose output in septic rats, but did not enhance glucose disposal. In vivo glucose uptake (Rg) by individual tissues was determined using the tracer 2-deoxyglucose technique. In nonseptic animals, MPA increased Rg in "working" muscles (heart and diaphragm; 12-fold and two-fold respectively), but not in "resting" skeletal muscles. MPA increased the Rg of heart and diaphragm to the same level in septic animals. Inhibition of fatty acid oxidation in nonseptic rats also enhanced Rg in liver (174%), spleen (158%), lung (153%), ileum (52%), skin (28%), kidney (115%), and epididymal fat (135%). In septic rats, MPA only increased Rg in the ileum (23%) and kidney (50%). This increased glucose uptake was independent of increases in plasma glucose and insulin concentrations. The infusion of heparin and intralipid, which increased circulating levels of fatty acids, failed to produce consistent changes in either the whole body glucose turnover or glucose uptake by individual tissues. We conclude that under basal in vivo conditions the inhibition of fatty acid oxidation suppresses glucose production and increases peripheral glucose disposal in nonseptic animals. These data support the presence of the glucose-fatty acid cycle in nonmuscle tissues and emphasizes its importance in whole body glucose homeostasis in situations where fatty acid oxidation is impaired. Infection increases glucose uptake by nonmuscle tissues which, for the most part, cannot be further enhanced by the inhibition of lipid oxidation. PMID- 1423927 TI - Regulation of platelet-derived growth factor ligand and receptor gene expression by alpha-thrombin in vascular smooth muscle cells. AB - Since the expression of genes for platelet-derived growth factor (PDGF)-A and PDGF beta-receptor are reciprocally regulated in vascular wall cells after balloon injury, we have investigated the ability of specific vasoactive molecules or growth factors to reproduce the injury pattern of gene expression in cultured rat smooth muscle cells (SMCs) and assessed the effect of inactivating alpha thrombin on injury-induced expression of PDGF-A mRNA by vascular wall cells in vivo. The molecules investigated, to which vascular SMCs may be locally exposed after mechanical injury, included vasoactive factors (alpha- and beta-adrenergic agonists, serotonin, histamine, angiotensin II, and endothelin) and growth factors (PDGF-AA, PDGF-BB, basic fibroblast growth factor, insulin-like growth factor, epidermal growth factor, and alpha-thrombin). In cultured rat SMCs, only alpha-thrombin (0.1-100 nM), among these compounds, produced the pattern of transiently increased PDGF-A and decreased PDGF beta-receptor mRNA. PDGF-B chain mRNA levels remained undetectable in these cultured SMCs. The dependence of these changes in gene expression on the proteolytic activity of alpha-thrombin was shown by the interruption of altered gene expression or DNA synthesis after incubating the cultured SMCs with covalently inactivated alpha-thrombin using D Phe-Pro-Arg chloromethyl ketone, a synthetic direct active-site irreversible inhibitor of alpha-thrombin. Continuous intravenous infusion of this synthetic antithrombin into baboons for 6 hours (100 nmol/kg per minute maintaining constant plasma levels of 3.0 +/- 0.5 microns/ml) after inducing balloon-catheter arterial injury also prevented the threefold increase in expression of PDGF-A mRNA characteristically exhibited by untreated mechanically injured vessels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423929 TI - HCO3(-)-dependent intracellular pH regulation in the premature myocardium. AB - This study investigated developmental changes in Na(+)-H+ exchange and HCO3(-)-Cl exchange activities in newborn and adult rabbit hearts. pHi was measured using the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in isolated myocytes. Myocardial mechanical function was measured in the isolated ventricular preparation. Intracellular acidosis with normal pHo was induced by an NH4Cl (10 mM) prepulse technique. Upon removal of NH4Cl, pHi fell transiently and then recovered toward the control level. In the HCO3-/CO2-buffered solution, the rate of recovery of pHi in the newborn was greater than in the adult. In the HCO3-/CO2 buffered solution, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of Na(+) H+ exchange, inhibited the recovery of pHi completely in the adult. In the newborn, however, significant recovery of pHi was observed in the presence of EIPA. In the presence of both EIPA and 4-acetamido-4'-isothiocyanatostilbene 2',2'-disulfonic acid (SITS), an inhibitor of HCO3(-)-Cl- exchange, the recovery of pHi was not observed in the two age groups. In the HEPES-buffered solution that did not contain HCO3-/CO2, the rate of recovery of pHi after NH4Cl removal was similar in the two age groups. In the HEPES-buffered solution, the recovery of pHi was completely inhibited by EIPA in the two age groups. In the presence of EIPA in the HCO3-/CO2-buffered solution, contractile function decreased during acidosis after NH4Cl removal and did not recover in the adult. In the newborn, significant recovery of contractile function was observed after NH4Cl removal in the presence of EIPA. The recovery of mechanical function observed in the presence of EIPA in the newborn was inhibited by SITS. These data suggest that, although there is no developmental change in the Na(+)-H+ exchange activity, HCO3(-)-Cl- exchange is more active in the premature myocardium. The presence of the HCO3(-)-Cl- exchanger is important in maintaining myocardial contractile function during acidosis, especially when Na(+)-H+ exchange is inhibited and may partly explain the greater resistance of the premature myocardium to acidosis. PMID- 1423928 TI - Effects of serotonin on intracellular pH and contraction in vascular smooth muscle. AB - Serotonin (5-HT) and other contractile agonists stimulate Na(+)-H+ exchange in vascular smooth muscle. Since intracellular alkalinization, per se, stimulates contraction, we tested whether 5-HT-induced contraction was associated with an increased pHi. In HCO3(-)-free buffer (pHo 7.4), 5-HT (10(-5) M) increased pHi, as measured by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein fluorescence, from 7.10 +/- 0.03 to 7.34 +/- 0.03 (p < 0.01) in primary cultures of canine femoral artery vascular smooth muscle cells grown to confluence in the presence of 10% fetal calf serum. In HCO3- buffer (24 mM, pHo 7.4), resting pHi was 7.26 +/- 0.04 (p < 0.01 versus HCO3(-)-free buffer) but was not altered by 5-HT. In both types of buffer, 5-HT stimulated 5-(N-ethyl-N-isopropyl)amiloride-sensitive 22Na+ uptake (Na(+)-H+ exchange). In HCO3- buffer and in Na(+)- and HCO3(-)-free buffer, 5-HT increased 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive 36Cl- uptake, suggesting that 5-HT stimulated Na(+)-independent Cl(-)-HCO3- and Cl(-)-Cl- exchange activities, respectively. Individual vascular smooth muscle cells were then cultured on rat tail tendon collagen gels in the presence of 0.5% fetal calf serum, and cell length and pHi were measured by video and epifluorescence microscopy. 5-HT contracted cells in a dose-dependent, reversible, and ketanserin-inhibitable manner. These cells, like cells grown in 10% fetal calf serum, exhibited Na(+)-H+ and Na(+)-independent Cl(-)-HCO3- exchange. In HCO3- buffer, 5-HT contracted cells without an associated change in pHi. We concluded the following: 1) 5-HT stimulated both Na(+)-H+ and Na(+) independent Cl(-)-HCO3- exchange activities in cultured vascular smooth muscle cells in parallel. 2) As a result of enhanced H+ and HCO3- efflux, pHi was not altered. 3) In the presence of HCO3-, 5-HT-induced contraction was not associated with a change in pHi. PMID- 1423932 TI - Age-related changes in fibronectin expression in spontaneously hypertensive, Wistar-Kyoto, and Wistar rat hearts. AB - The effects of age and blood pressure on fibronectin expression in the rat heart were studied in the normotensive Wistar and Wistar-Kyoto (WKY) strains and in the spontaneously hypertensive rat (SHR). Fibronectin mRNA expression decreased threefold between 10 and 40 weeks of age in Wistar hearts, with changes of similar magnitude occurring between 6 and 24 weeks in WKY rats. In contrast, no decrease in fibronectin mRNA was observed in SHR hearts during this time span. These results are in contrast to changes observed previously in the aorta, where an increase in fibronectin mRNA occurred with age in all three rat strains. Ribonuclease protection analysis showed a small age-specific increase in the relative content of EIIIA+ fibronectin mRNA isoforms in hearts from Wistar rats, whereas no change was found in the relative amount of either EIIIA or EIIIB isoforms in SHR hearts. Changes similar to those observed for fibronectin mRNA, although of different magnitudes, were observed in mRNA levels for collagen alpha 1(III) and beta 1 integrin. In Wistar hearts, collagen alpha 1(III) mRNA levels decreased fivefold to sixfold between 10 and 40 weeks of age, whereas a twofold to threefold decrease in beta 1 integrin was observed in WKY hearts between 6 and 24 weeks of age. Western blot analysis revealed a positive correlation between fibronectin mRNA and protein for age-dependent changes in ventricular tissue but not in the atria, suggesting that the regulation of fibronectin expression during the changes common to both aging and hypertrophy could involve both transcriptional and posttranscriptional mechanisms. PMID- 1423931 TI - Decreased myofilament responsiveness in myocardial stunning follows transient calcium overload during ischemia and reperfusion. AB - The purpose of this study was to test the hypothesis that abnormal intracellular calcium handling characterizes myocardial stunning. Isolated, isovolumic, buffer perfused ferret hearts were loaded with the bioluminescent calcium indicator aequorin for simultaneous measurement of individual calcium transients and left ventricular pressure. After 15 minutes of global ischemia and 20 minutes of reperfusion, left ventricular developed pressure was significantly reduced (75 +/ 7 versus 93 +/- 6 mm Hg, p < 0.05). During ischemia, [Ca2+]i levels were significantly elevated compared with preischemic levels, both during systole (1.38 +/- 0.31 versus 0.88 +/- 0.2 microM, p < 0.05) and end diastole (0.85 +/- 0.16 versus 0.38 +/- 0.13 microM, p < 0.05). Early during reperfusion, [Ca2+]i was also significantly elevated during systole (1.63 +/- 0.44 versus 0.88 +/- 0.20 microM, p < 0.05) and end diastole (0.75 +/- 0.15 versus 0.38 +/- 0.13 microM, p < 0.05). After 20 minutes of reperfusion, myocardial stunning occurred, but [Ca2+]i was not significantly different from preischemic levels. Thus, myocardial stunning does not result from decreased levels of activator calcium. The force-pCa relation generated by the stunned hearts was shifted downward compared with that generated by the control hearts, consistent with a decrease in maximum calcium-activated force (Fmax). At steady state during tetanus, the decrease in Fmax was confirmed, but there was no significant difference in the slope of the force-pCa relation of the stunned hearts versus controls. Thus, we conclude that stunned myocardium is characterized by decreased Fmax without desensitization of the myofilaments to [Ca2+]i.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423933 TI - Body surface mapping of ectopic left ventricular activation. QRS spectrum in patients with prior myocardial infarction. AB - To improve electrocardiographic localization of the site of origin of ectopic left ventricular (LV) impulse formation in the heart with prior myocardial infarction, 62-lead body surface QRS integral maps were studied during LV pacing at a total of 221 endocardial sites in 14 patients with previous anterior (AMI), inferior (IMI), lateral (LMI), or anterior and inferior (AMI/IMI) myocardial infarction. The anatomic location of each pacing site was computed using digitized biplane fluoroscopic images and plotted on standardized LV endocardial polar projections. A data base of characteristic AMI and IMI mean QRS integral maps was developed after visually selecting subgroups with nearly identical QRS integral morphology from the ectopic activation sequences produced at 110 sites in eight patients with AMI and at 66 sites in four patients with IMI. Intrasubgroup pattern uniformity and intersubgroup pattern variability were statistically verified. The endocardial pacing site locations belonging to each AMI and IMI subgroup were depicted as segments on the respective LV polar projections. In patients with AMI, a total of 18 typical mean QRS integral patterns were obtained, whereas 22 different mean total QRS integral patterns showing more substantial intersubgroup variation were acquired in patients with IMI. Posterolateral regions exhibited a relatively low electrocardiographic sensitivity (six AMI and five IMI patterns) as compared with anteroseptal regions (12 AMI and 17 IMI patterns). Total QRS integral patterns obtained at 24 sites in one patient with LMI were largely compatible with the IMI mean total QRS integral patterns, whereas the majority of total QRS integral patterns acquired at 21 sites in one patient with AMI/IMI corresponded with the AMI mean total QRS integral patterns. The results show that total body surface QRS integral maps generated during LV pacing in patients with prior myocardial infarction cluster by pattern and that each QRS integral pattern is related to a circumscribed endocardial segment of ectopic impulse formation. The relation between a given QRS integral pattern and the position and size of the corresponding paced segment is dependent on infarct location. The present infarct-specific data base of characteristic total body surface QRS integral patterns provides a clinical tool to obtain detailed electrocardiographic localization of ventricular arrhythmias in patients with previous myocardial infarction. PMID- 1423930 TI - Activation of ATP-sensitive K+ channels by cromakalim. Effects on cellular K+ loss and cardiac function in ischemic and reperfused mammalian ventricle. AB - Pharmacological modulation of [K+]o accumulation and action potential changes during acute myocardial ischemia is under evaluation as a promising new antiarrhythmic and cardioprotective strategy during myocardial ischemia and reperfusion. We studied the effects of cromakalim, a K+ channel opener that activates ATP-sensitive K+ channels, in isolated arterially perfused rabbit interventricular septa subjected to ischemia and reperfusion and, through use of the patch clamp technique, in inside-out membrane patches excised from guinea pig ventricular myocytes. During aerobic perfusion, 5 microM cromakalim shortened action potential duration (APD) from 217 +/- 7 to 201 +/- 10 msec, had no effect on [K+]o, and reduced tension by 17 +/- 3% (n = 11). During ischemia, pretreatment with 5 microM cromakalim resulted in 1) more rapid APD shortening (71 +/- 9 versus 166 +/- 7 msec at 10 minutes and 63 +/- 12 versus 122 +/- 8 msec at 30 minutes), 2) similar [K+]o accumulation after 10 minutes (8.9 +/- 0.3 versus 9.6 +/- 0.5 mM) but a trend toward increased [K+]o accumulation after 30 minutes (11.0 +/- 1.7 versus 9.6 +/- 1.0 mM), and 3) similar times for tension to decline to 50% of control (2.14 +/- 0.16 versus 2.14 +/- 0.19 minutes) but shorter time to fall to 20% of control (4.34 +/- 0.33 versus 4.90 +/- 0.22 minutes; p = 0.003). After 60 minutes of reperfusion following 30 minutes of ischemia, recovery of function was similar, with a trend toward better recovery of developed tension (to 58 +/- 9% versus 39 +/- 10% of control; p = 0.18) and tissue ATP levels in cromakalim-treated hearts but no differences in APD or rest tension. Thus, 5 microM cromakalim had mild effects in normal heart but greatly accelerated APD shortening during ischemia without markedly increasing [K+]o accumulation, possibly because the more rapid APD shortening reduced the time averaged driving force for K+ efflux through ATP-sensitive K+ channels. A significant cardioprotective effect during 30 minutes of ischemia plus 60 minutes of reperfusion could not be demonstrated in this model. In excised membrane patches studied at room temperature, the ability of cromakalim to activate ATP sensitive K+ channels was significantly potentiated by 100 microM but not 15 microM cytosolic ADP, suggesting that in addition to the modest fall in cytosolic ATP during early ischemia, the rapid increases in cytosolic ADP may further sensitize cardiac ATP-sensitive K+ channels to activation by cromakalim.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423934 TI - Ventricular loading is coupled with DNA synthesis in adult cardiac myocytes after acute and chronic myocardial infarction in rats. AB - To determine whether the overload associated with myocardial infarction and ventricular failure in rats is coupled with activation of DNA synthesis in the remaining left and right ventricular myocytes, flow cytometric analysis was performed on myocyte nuclei prepared from both ventricles 7 and 30 days after coronary occlusion. In addition, oral captopril was administered in separate groups of control and experimental rats to establish whether a relation existed between attenuation of ventricular loading and magnitude of DNA synthesis in myocytes. Results demonstrated that left ventricular failure and right ventricular dysfunction at 7 days after infarction were biventricularly associated with marked increases in the number of myocyte nuclei in the G2M phase of the cell cycle. In contrast, the fraction of nuclei in the G0+G1 phase decreased. In comparison with the earlier time point, the 30-day interval was characterized by a significant magnitude of cardiac hypertrophy, a moderate amelioration of ventricular pump function, and a decrease in the percentage of myocyte nuclei in the G2M phase in both ventricles. However, 30 days after infarction, the number of right ventricular myocyte nuclei in the S and G2M phases remained elevated with respect to control animals. Captopril therapy reduced the extent of ventricular loading and the population of myocyte nuclei in the cell cycle at 7 days. In conclusion, DNA synthesis in myocyte nuclei may represent an important adaptive component of the myocardial response to infarction. PMID- 1423935 TI - Age-related appearance of outward currents may contribute to developmental differences in ventricular repolarization. AB - Ventricular repolarization significantly influences contractility, refractoriness, and ion channel state. Factors affecting repolarization will thus affect these secondary phenomena. To understand the influence of age on ventricular repolarization, we studied neonatal, young, and adult dogs using electrocardiogram, action potential, and whole-cell voltage-clamp recordings from single epicardial myocytes. Hearts of neonatal and 57-58-day-old dogs require a significantly longer time for repolarization than those of adult dogs, as determined by analysis of rate-corrected QT and JT (QT minus QRS) intervals. Epicardial action potentials of neonates are significantly longer than those of adults, as determined by measurements of duration at 50% and 90% repolarization. The adult action potential is characterized by a large phase 1 notch that is absent from neonatal recordings. This notch develops between 58 and 64 days of age, and by 64-68 days of age, it is equal to that in adults. In addition, action potentials recorded from adult and young epicardial muscle are more greatly affected by rapid pacing and superfusion of 2 mM 4-aminopyridine than are potentials recorded from neonatal tissue. Whole-cell voltage-clamp recordings reveal a 4-aminopyridine-sensitive transient outward current in adult myocytes that is absent from neonatal myocytes. The correlation between developmental changes in the 4-aminopyridine-sensitive current, the action potential, and the QT interval suggests that the transient outward current may be an important determinant in the relation between age and repolarization. PMID- 1423936 TI - Accumulation and assembly of myosin in hypertrophic cardiomyopathy with the 403 Arg to Gln beta-myosin heavy chain mutation. AB - The sarcomeric proteins and organization of cardiac myofibrils appeared intact in multiple unrelated patients with hypertrophic cardiomyopathy. In two subjects demonstrating the missense mutation at position 403 (Arg to Gln) in the beta myosin heavy chain gene, total myosin and immunoreactive beta-myosin heavy chain levels were similar to those found in other patients with hypertrophic cardiomyopathy and various disease control subjects. No alteration in expression of the cardiac alpha-myosin heavy chain gene was observed. These results are consistent with the examined myosin heavy chain mutation, permitting proper accumulation and assembly of myosin while primarily impairing contractile function. The characteristic myocyte disarray would appear likely to be a secondary consequence of the mutations. PMID- 1423937 TI - Lysophosphatidylcholine inhibits surface receptor-mediated intracellular signals in endothelial cells by a pathway involving protein kinase C activation. AB - Lysophosphatidylcholine (lysoPC) transferred from oxidatively modified low density lipoprotein (Ox-LDL) to the endothelial surface membrane has been shown to produce a selective unresponsiveness to cell surface receptor-regulated endothelium-dependent relaxation (EDR) in the rabbit aorta. To determine its mechanism we examined the effects of lysoPC on endothelial surface receptor mediated transmembrane signals. Incubation for 1 minute with palmitoyl lysoPC (5 10 microM) decreased thrombin (Th, 2 units/ml)- or histamine (His, 0.1 mM) stimulated inositol 1,4,5-trisphosphate (IP3) production in primary cultures of human umbilical vein endothelial cells (HUVECs). LysoPC also decreased Th- or His induced intracellular calcium ([Ca2+]i, fura 2) elevation. Pretreatment with protein kinase C (PKC) inhibitors staurosporine (100 nM) or H-7 (50 microM) prevented the inhibitory actions of lysoPC, but HA-1004 had no effect. Incubation for 5 minutes with phorbol 12-myristate 13-acetate (PMA, 100 nM) produced the inhibitory actions on the Th- or His-induced intracellular signals, which closely mimic those exhibited by lysoPC. However, the inhibitory effect of lysoPC was lost in cells that were depleted of PKC by pretreatment for 24 hours with 100 nM PMA. Furthermore, incubation of the cells for 1 minute with lysoPC stimulated PKC activity in the membrane fraction. In organ chamber experiments with porcine coronary artery rings, pretreatment with staurosporine (20 nM) attenuated lysoPC induced impairment of EDR in response to Th. These results indicate that lysoPC, which accumulates in Ox-LDL and atherosclerotic arterial walls, inhibits the early transmembrane signaling pathway in endothelial cells, and PKC activation could at least partially be involved in the negative regulation by lysoPC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423938 TI - Endothelium-derived relaxing factor modulates platelet aggregation in an in vivo model of recurrent platelet activation. AB - It has been shown that endothelium-derived relaxing factor (EDRF) may inhibit platelet aggregation in vitro through activation of platelet-soluble guanylate cyclase. To assess whether EDRF may also affect platelet function in vivo, intravascular platelet aggregation was initiated by placing an external constrictor around endothelially injured rabbit carotid arteries. Carotid blood flow velocity was measured continuously by a Doppler flow probe placed proximal to the constrictor. After placement of the constrictor, cyclic flow reductions (CFRs), due to recurrent platelet aggregation, developed at the site of the stenosis. After CFRs were observed for 30 minutes, a solution of authentic nitric oxide (NO, n = 10) was infused into the carotid artery via a small catheter placed proximally to the stenosis. Before infusion of NO, CFR frequency averaged 18.3 +/- 2.9 cycles per hour, and CFR severity (lowest carotid blood flow as percentage of baseline values) was 6 +/- 1%. NO completely inhibited CFRs in all animals, as shown by the normal and constant pattern of carotid blood flow (CFR frequency, 0 cycles per hour, p < 0.001; carotid blood flow, 92 +/- 5%, p = NS versus baseline). These effects were transient; CFRs were restored spontaneously within 10 minutes after cessation of NO infusion. After CFRs returned, S-nitroso cysteine (S-NO-cys), a proposed form of EDRF, was infused into the carotid artery. S-NO-cys also abolished CFRs in all animals but at a significantly lower dose than NO (0.3 +/- 0.1 versus 12 +/- 4 nmol/min). The role of endogenously released EDRF in modulating in vivo platelet function was then tested in additional experiments. In 10 animals, endogenous release of EDRF was stimulated by infusing acetylcholine into the aortic root during CFRs. Infusion of acetylcholine was also associated with a complete inhibition of CFRs, similar to that observed during exogenous infusion of NO or S-NO-cys. These antithrombotic effects of acetylcholine were completely lost when EDRF synthesis was prevented by administration of the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). Furthermore, in six additional rabbits the basal release of EDRF was blocked by L NMMA after CFRs had been previously abolished with aspirin or the combination of aspirin and ketanserin, a serotonin S2 receptor antagonist. L-NMMA caused restoration of CFRs in all animals, indicating that even the basal release of EDRF is important in modulating platelet reactivity in vivo. Taken together, the data of the present study demonstrate that endogenous EDRF might importantly contribute to the modulation of platelet function in vivo. PMID- 1423939 TI - Coronary blood flow after the regression of pressure-overload left ventricular hypertrophy. AB - Abnormal coronary blood flow (CBF) in long-standing left ventricular (LV) pressure-overload hypertrophy has been associated with ischemia and LV dysfunction. Thus, goals of therapy in pressure overload are not only the relief of the overload itself but also regression in hypertrophy and subsequent improvement in CBF. However, little is known about CBF in humans or in large mammals after the relief of pressure overload, when the hypertrophy has regressed. This study was performed to test the hypothesis that, even 6 months after the relief of pressure overload in the dog, CBF would still be abnormal. Three groups of dogs were studied: 1) normal control dogs (NL group), 2) dogs with LV pressure-overload hypertrophy (LVH group), and 3) dogs that had developed LV pressure-overload hypertrophy but in whom the pressure overload was relieved 6 months before the final study (LVH Reg group). CBF was studied in conscious dogs by use of the radiolabeled microsphere technique at rest, during rapid atrial pacing, and during maximum coronary vasodilation produced by adenosine infusion. The ratio of LV weight (g) to body weight (kg) (LVBW) was 4.2 +/- 0.3 in the NL group, 7.1 +/- 0.6 in the LVH group, and 7.7 +/- 0.5 in the LVH Reg group before pressure-overload relief (p = NS, LVH versus LVH Reg). Six months after removal of the pressure overload, the LVBW in the LVH Reg group had fallen to 5.5 +/- 0.3 (p < 0.05), but this LVBW was still greater than that in the NL group (p < 0.05). During rapid atrial pacing, endocardial and epicardial CBF rose significantly in NL dogs. However, during rapid atrial pacing, endocardial CBF fell from 1.18 +/- 0.22 to 0.7 +/- 0.20 ml/min per gram in the LVH group (p < 0.05) and did not rise in the LVH Reg group. During adenosine infusion, endocardial blood flow increased in NL dogs from 1.63 +/- 0.13 to 4.0 +/- 0.3 ml/min per gram and increased to a similar level in the LVH Reg group. Although CBF increased during adenosine infusion in the LVH group, the increase was less than that in the NL or LVH Reg group (p < 0.05). Minimum coronary vascular resistance was similar in NL dogs (14 +/- 2 units) and LVH Reg dogs (18 +/- 3 units, p = NS) but was significantly elevated (32 +/- 10 units) in LVH dogs (p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1423940 TI - Characterization of angiotensin II receptor subtypes in rat heart. AB - Angiotensin II exerts positive inotropic and chronotropic effects on the mammalian heart by binding to specific membrane receptors. Recently, two subtypes of angiotensin II receptors (AT1 and AT2) have been distinguished by using the nonpeptide antagonists losartan (previously known as DuP 753) and PD123177. To evaluate the tissue distribution and subtypes of angiotensin II receptors in rat heart, we performed a 125I-[Sar1,Ile8]angiotensin II in situ binding assay on tissue sections obtained from adult Sprague-Dawley rats (10 and 14 weeks old). Binding specificity was verified by competition with unlabeled [Sar1]angiotensin II. Distribution of AT1 and AT2 receptors was determined by competition with losartan and PD123177, respectively, and the density of the receptors was quantified by emulsion autoradiography. Angiotensin II receptors were widely distributed throughout the heart, with each receptor subtype accounting for approximately 50% of the specific binding. Binding density was comparable in the atria, right and left ventricles, intraventricular septum, and sinoatrial node, whereas it was significantly greater in the atrioventricular node. The AT1 receptor appears to interact with guanidine nucleotide regulatory proteins, because GTP-gamma-S causes dissociation of the radioligand from this receptor. In contrast, the AT2 receptor does not appear to directly interact with guanine nucleotide regulatory proteins, inasmuch as radioligand dissociation from this receptor subtype is not affected by GTP-gamma-S. Because angiotensin II has been reported to have growth-potentiating effects in several tissues, we examined angiotensin II receptors in fetal (embryonic days 16 and 19) and neonatal (1-, 2 , 3-, and 10-day-old) rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423942 TI - Effect of inhibition of endopeptidase 24.11 on responses to angiotensin II in human volunteers. AB - The effects of endopeptidase 24.11 inhibition on angiotensin-induced changes in plasma angiotensin II, aldosterone, and atrial natriuretic factor concentrations and blood pressure were assessed in normal volunteers. Two groups, each consisting of eight normal volunteers, received stepwise infusions of angiotensin II (2, 4, and 8 ng/kg per minute) on day 5 of dose administration with 25 mg every 12 hours (group 1) or 100 mg every 12 hours (group 2) of an oral inhibitor of endopeptidase 24.11 (UK 79300, candoxatril) or placebo in balanced randomized, double-blind, placebo-controlled crossover studies. Both doses of candoxatril significantly enhanced achieved plasma angiotensin II concentrations during infusions (group 1, p < 0.001; group 2, p < 0.01; overall treatment effect for combined data, p < 0.001). This effect was most pronounced at the highest dose of angiotensin II (treatment-time interaction, p < 0.0001 for combined data) and tended to be more marked with the higher dose of candoxatril (treatment-group interaction, p = 0.08). The pressor response to angiotensin II was clearly enhanced by the lower dose of candoxatril; peak systolic and diastolic pressures exceeded placebo values by approximately 10 mm Hg (p < 0.001 and p < 0.05 for systolic and diastolic pressures, respectively). This effect of candoxatril was absent in group 2, which (unlike group 1) had exhibited a modest natriuretic response (sustained cumulative negative sodium balance, -70 +/- 21 mmol; p < 0.01) to the higher dose of inhibitor. Baseline plasma aldosterone concentrations and the incremental aldosterone response to angiotensin II infusions were not significantly altered by low-dose (group 1) candoxatril.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423941 TI - Coronary collateral development in swine after coronary artery occlusion. AB - We have quantified the development of the coronary collateral circulation in the pig. The collateral circulation was induced to grow by placing an ameroid occluder on the left circumflex coronary artery. Two to 16 weeks after ameroid placement, the coronary collateral circulation was identified after the injection of several colors of a silicone polymer into the coronary arteries and the aorta. We identified intercoronary and extracardiac collaterals and quantified their number, location, size, and wall thickness. Intercoronary collaterals grew to a level that represents a 14-fold increase in normal collateral blood flow under resting conditions compared with the values in an animal not subjected to coronary artery occlusion. Extracardiac collaterals could potentially supply approximately 30% of resting flow. The sources of the extracardiac collaterals were the bronchial and internal mammary arteries. Coronary collateral morphometry and DNA synthesis in the pig heart also were examined. Coronary collaterals had significantly less smooth muscle than did normal arterioles. This may account, in part, for the reduced response of the coronary collaterals to vasodilators. We observed intense DNA synthesis in endothelial and smooth muscle cells in the first 2 or 3 weeks of ischemia. However, DNA synthesis rapidly ceased after this time, coincident with coronary collateral reserve values (ischemic/nonischemic regional blood flow ratios during maximal vasodilation) reaching their maximum level. This suggests that failure of the vessels to continue proliferating accounts for the occurrence of the plateau in blood flow levels. PMID- 1423943 TI - Optimization of retroviral vector-mediated gene transfer into endothelial cells in vitro. AB - Retroviral vector-mediated gene transfer into endothelial cells is relatively inefficient with transduction rates as low as 1-2% in vitro and even lower in vivo. To increase the efficiency of gene transfer into endothelial cells, we used retroviral vectors expressing beta-galactosidase and urokinase and measured endothelial cell transduction efficiencies with quantitative assays for beta galactosidase and urokinase protein. We evaluated several techniques reported to improve the efficiency of retroviral transduction in vitro, including 1) extended periods of exposure to vector, 2) repeated exposures to vector, 3) maximization of the ratio of vector particles to endothelial cells by increasing the volume and concentration of vector particles or by decreasing the number of endothelial cells exposed, 4) cocultivation of endothelial cells with vector-producing cells, and 5) variation of the type and concentration of polycation used with the retroviral vector. Only the use of more concentrated (higher titer) vector containing supernatant and the use of the polycation DEAE-dextran improved the efficiency of gene transfer into endothelial cells in vitro. In an optimized transduction protocol, a 60-second exposure to 1 mg/ml DEAE-dextran followed by a single 6-hour exposure to supernatant of a titer of 10(5)-10(6) colony-forming units/ml resulted in transduction efficiencies of 50-90% with both vectors. Decreasing the time of the supernatant exposure to 15 minutes permitted transduction efficiencies of 15-20% while significantly minimizing the duration of the transduction. Therefore, the optimized protocol allows high efficiency in vitro gene transfer into endothelial cells within several hours. The briefer protocol may prove useful for in vivo gene transfer in which the time of exposure to the supernatant is limited. PMID- 1423944 TI - Kinetics of C5a release in cardiac lymph of dogs experiencing coronary artery ischemia-reperfusion injury. AB - Previous studies of myocardial ischemia suggest that complement activation may play a central role in the inflammatory response during reperfusion. Our previous work has demonstrated neutrophil chemotactic activity to be present in reperfusion canine cardiac lymph after myocardial ischemia and infarction. To evaluate the contribution of the complement-dependent anaphylatoxin C5a to this neutrophil chemotactic activity, rabbit antiserum to canine C5a was prepared. At dilutions > 1:500 but < 1:2,000, the antiserum abolished the ability of zymosan activated dog serum to induce a ruffled, bipolar morphology in isolated neutrophils used as a bioassay of chemotactic stimulation. This antiserum did not affect similar morphological changes in neutrophils exposed to platelet activating factor (10(-7)-10(-6) M) or recombinant human interleukin-8 (10(-9) 10(-8) M); thus, we deemed it functionally specific for canine C5a. In a pattern similar to what we previously reported, cardiac lymph collected before a 1-hour ligation of the left circumflex coronary artery had little ability to alter the morphology of canine neutrophils (shape change index, 11.3 +/- 4.6, mean +/- SEM; n = 7), but by 1 hour of reperfusion, lymph activated neutrophils significantly in five of seven dogs (mean shape change index, 72.6 +/- 17.7; p < 0.01). At 2 hours of reperfusion, neutrophil activation by lymph occurred in six of seven dogs (mean shape change index, 103.1 +/- 22.2). At 3 hours of reperfusion, cardiac lymph of only three of six dogs caused neutrophil activation, and at 4 hours of reperfusion, this activity was evident in lymph from only two of five dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423946 TI - Active skeletal muscle mass and cardiopulmonary reserve. Failure to attain peak aerobic capacity during maximal bicycle exercise in patients with severe congestive heart failure. AB - BACKGROUND: In addition to depressed cardiac reserve, peripheral factors may contribute to limit maximal exercise capacity in patients with congestive heart failure (CHF). To investigate the role of reduced active skeletal muscle mass, peak oxygen uptake (VO2, milligrams per kilogram per minute) was determined during maximal symptom-limited exercise involving the lower limbs (LL) alone and the lower limbs and upper limbs (LL+UL) combined in patients with CHF and in normal subjects of similar age and sex. METHODS AND RESULTS: LL bicycle exercise was performed upright with a ramp protocol and continuous expired gas analysis. When respiratory exchange ratio (RER) reached 1.0, UL exercise was initiated at constant load with the use of a cranking device positioned at shoulder level. LL exercise alone and combined LL+UL exercise were performed on separate days in randomized order by 24 patients with CHF and seven normal subjects. In patients with CHF, peak VO2 was greater during combined LL+UL exercise than during LL exercise alone, i.e., 15.8 +/- 0.8 versus 14.2 +/- 0.9 ml.kg-1.min-1 (p < 0.001), whereas in normal subjects, maximal VO2 was similar during the two tests, i.e., 26.7 versus 26.2 ml.kg-1.min-1 (NS). The increase in peak VO2 during combined LL+UL exercise relative to LL exercise alone was almost exclusively observed in patients with peak VO2 < 15 ml.kg-1.min-1 (mean increase, 21.7 +/- 4.1%). Peak VO2 during combined LL and UL exercise did not increase relative to LL exercise alone in patients with peak VO2 > 15 ml.kg-1.min-1 and in normal subjects of similar age and sex, i.e., 0.1 +/- 4.0% and 2.0 +/- 2.3% respectively. CONCLUSIONS: In contrast to normal subjects and patients with moderate CHF, patients with severe CHF do not exhaust their cardiopulmonary reserve during symptom-limited maximal LL exercise on a bicycle. PMID- 1423945 TI - Platelet-derived growth factor-BB-induced suppression of smooth muscle cell differentiation. AB - Previously, we demonstrated that treatment of postconfluent quiescent rat aortic smooth muscle cells (SMCs) with platelet-derived growth factor (PDGF)-BB dramatically reduced smooth muscle (SM) alpha-actin synthesis. In the present studies, we focused on the expression of two other SM-specific proteins, SM myosin heavy chain (SM-MHC) and SM alpha-tropomyosin (SM-alpha TM), to determine whether the actions of PDGF-BB were specific to SM alpha-actin or represented a global ability of PDGF-BB to inhibit expression of cell-specific proteins characteristic of differentiated SMCs. SM-MHC and SM-alpha TM expression were assessed by one- or two-dimensional gel electrophoretic analysis of proteins from cells labeled with [35S]methionine, as well as by Northern analysis of mRNA levels. Synthesis of both SM-specific proteins was decreased by 50-70% in PDGF-BB -treated cells as compared with cells treated with PDGF vehicle. Treatment of cells with 10% fetal bovine serum, which produced a mitogenic effect equivalent to that of PDGF-BB, decreased SM-MHC synthesis by 40% but increased SM-alpha TM synthesis. SM-MHC and SM-alpha TM mRNA expression was decreased by 80% at 24 hours in PDGF-BB--treated postconfluent SMCs, whereas treatment with 10% fetal bovine serum did not decrease the expression of SM-alpha TM mRNA but did inhibit SM-MHC mRNA expression by 36%. Consistent with the absence of detectable PDGF alpha-receptors on these cells, PDGF-AA had no effect on either mitogenesis or expression of SM-MHC or SM-alpha TM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1423947 TI - Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects. AB - BACKGROUND: Four-hour 201Tl redistribution images underestimate myocardial viability in patients with coronary artery disease (CAD). Because 4-hour defects often redistribute late, delayed imaging may enhance assessment of tissue viability. Myocardial metabolic activity was therefore assessed with positron emission tomography (PET) in 26 CAD patients with impaired ventricular function (ejection fraction, 32.1 +/- 13.9%) and 24-hour single-photon emission computed tomography (SPECT) 201Tl defects. METHODS AND RESULTS: On circumferential profile analysis, PET ischemia was defined by preserved glucose metabolism in hypoperfused myocardium, and PET infarction was defined by concordant reductions in perfusion and metabolism. On 19 stress-redistribution and seven rest redistribution SPECT studies, four observers visually scored 201Tl activity in eight segments on a scale from 0 (normal) to 3 (complete defect). Using an improvement in visual score > or = 0.75 to define redistribution, there were 100 fixed, 17 partially reversible, and 12 completely reversible defects. PET identified tissue metabolic activity in 51 (51%) segments with fixed defects (21 PET ischemia, 30 PET normal) and nine (53%) segments with partially reversible defects (five PET ischemia, four PET normal). When grouped by 24-hour score, the proportion of fixed defects with metabolic activity varied from 84% (scores < or = 1.4) to 15% (scores > 2.6). For partially reversible defects, only 53% with scores < 2.0 and one of two with scores > or = 2.0 were considered metabolically viable on PET. Of 12 completely reversible defects, six (50%) were normal, five (42%) had PET ischemia, and one (8%) had PET infarction. The proportion of fixed defects with metabolic activity did not depend on whether a rest or stress study was performed or on the change in visual score used to define 201Tl redistribution (0.25, 0.50, 0.75, and 1.00). CONCLUSIONS: In CAD patients, PET identifies glucose metabolic activity in the majority of fixed 24-hour 201Tl defects. However, very severe (near-complete) 24-hour 201Tl defects are less likely to exhibit metabolic activity on PET imaging than are defects with less pronounced reductions in segmental 201Tl activity. PMID- 1423948 TI - Highly variable anticoagulant response after subcutaneous administration of high dose (12,500 IU) heparin in patients with myocardial infarction and healthy volunteers. AB - BACKGROUND: In this study, the anticoagulant response of 12,500 IU heparin s.c. was investigated in patients with myocardial infarction and healthy volunteers to determine variabilities in response and modifying factors. METHODS AND RESULTS: On the fourth day after thrombolytic therapy, blood samples were taken before and at frequent intervals until 10 hours after the injection of 12,500 IU heparin s.c. Plasma anti-Xa activity, anti-IIa activity, and the activated partial thromboplastin time (APTT) were measured in addition to body weight and thickness of the abdominal subcutaneous fat layer. Contrary to expectations, the increase of anti-Xa activity, anti-IIa activity, and APTT compared with baseline (predrug) levels was very small, with an average maximal APTT of 42.6 seconds (SD, 12.4 seconds; range, 30.4-70.7 seconds). Subsequently, the influence of the length of the injection needle on the anticoagulant effect of 12,500 IU heparin s.c. was studied in 10 healthy volunteers to find a factor that could be responsible for the poor response in the patients. The length of the injection needle did not influence the anticoagulant effect of heparin. Large interindividual and intraindividual variabilities were seen in the volunteers. The majority of volunteers had minimal prolongation of the APTT, but very strong prolongation was also seen (maximal APTT, 163 seconds). There was no correlation between the abdominal skinfold thickness and anti-Xa activity, anti-IIa activity, or APTT (p > 0.05), but in the patient study, there was a correlation between weight and anti-Xa activity and anti-IIa activity (p < 0.05), and in the volunteer study, there was a correlation between weight and anti-Xa activity and APTT (p < 0.05). CONCLUSIONS: Subcutaneous administration of heparin in a fixed dose for prophylactic and therapeutic purposes may be inadequate because of the large interindividual and intraindividual variations in anticoagulant effect. PMID- 1423950 TI - Intravascular ultrasound evaluation of the effect of rotational atherectomy in obstructive atherosclerotic coronary artery disease. AB - BACKGROUND: High-speed rotational atherectomy uses a diamond-coated, elliptical burr to abrade occlusive atherosclerosis, especially noncompliant calcified plaque. METHODS AND RESULTS: Intravascular ultrasound (IVUS) was used to analyze 28 patients after atherectomy. Arteries treated and imaged were left main (three), left anterior descending (12), left circumflex (five), right coronary (seven), and saphenous vein graft (one). Twenty patients had adjunct balloon angioplasty. Twenty-two (79%) target lesions were calcified; the intimal arc of calcium was 160 +/- 126 degrees (range, 0-360 degrees). After atherectomy, the intima-lumen interface was unusually distinct and circular. The lumen was larger than the largest burr used for both stand-alone (1.19 +/- 0.19-fold the largest burr size) and adjunct balloon procedures (1.30 +/- 0.15-fold the largest burr). Three-dimensional reconstruction of the ultrasound images showed a smooth lumen, especially in calcified plaque. Deviations from cylindrical geometry occurred only in areas of soft plaque or superficial tissue disruption of calcified plaque. Five patients were studied before and after rotational atherectomy. IVUS showed an increase in lumen size, a decrease in plaque-plus-media area and in arc of target lesion calcification, and no change in target lesion external elastic membrane cross-sectional area. CONCLUSIONS: Rotational atherectomy causes atheroablation with only moderate evidence of barotrauma in heavily calcified arteries, even after adjunct balloon angioplasty. The lumen is cylindrical, especially in areas of calcified plaque, and somewhat larger than the largest burr tip used. PMID- 1423949 TI - Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone. AB - BACKGROUND: Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times. METHODS AND RESULTS: Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy. CONCLUSIONS: An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug induced torsade de pointes. PMID- 1423951 TI - Restenosis after directional coronary atherectomy. Effects of luminal diameter and deep wall excision. AB - BACKGROUND: Deep wall excision during directional atherectomy has been reported in one study to increase the risk of subsequent restenosis. On the other hand, we have observed that the probability of late (6-month) restenosis is reduced by maximizing postprocedure luminal diameter. Although such maximal luminal enlargement by directional atherectomy has not increased procedural complications in our experience, it might well increase the incidence of subintimal (deep wall component) recovery. We performed this study to evaluate the relative influences of luminal enlargement and deep wall component excision on postatherectomy restenosis. METHODS AND RESULTS: Atherectomy resulted in a 7 +/- 15% residual stenosis with < 0.5% incidence of angiographic vessel perforation. The minimal luminal diameter of each lesion was measured before and after intervention in 413 lesions, 389 (94%) of which had histological analysis of the excised specimens. Specimens were categorized by the deepest layer retrieved: type I (recovery of intima alone, n = 141), type II (recovery of media, n = 79), and type III (recovery of adventitia, n = 65). Repeat angiographic measurement of minimal luminal diameter was available for 329 (80%) segments 6 months after atherectomy. Compared with the 32% restenosis rate for type I excision, there was no increase in restenosis (stenosis > 50%) for type II, type III, or types II+III (p = 0.86). Stratification by vessel characteristics also failed to show any association between restenosis and deep wall component recovery in any subgroup, including native coronary (p = 0.85), left anterior descending coronary artery (p = 0.70), right coronary artery (p = 0.51), saphenous graft (p = 0.78), or prior restenosis lesions (p = 0.98). Paradoxically, the recovery of adventitia (type III excision) was associated with a lower late percent stenosis (p = 0.03) and a trend toward less restenosis (p = 0.11) compared with type I excisions. A multiple logistic regression model was constructed that demonstrated immediate postprocedure luminal diameter (p = 0.02) to be an independent determinant of restenosis. In this model, the presence of deep wall components (type II+III) did not adversely affect (p = 0.86) restenosis, but the recovery of adventitia was associated with an independent trend toward reduced restenosis (p = 0.06). CONCLUSIONS: The immediate goal of directional atherectomy should be to safely provide the largest lumen possible in order to reduce restenosis. The recovery of deep wall components does not appear to jeopardize the beneficial effect that obtaining a large immediate postprocedure lumen diameter has on reducing the incidence of late restenosis. PMID- 1423952 TI - Randomized trial of late elective angioplasty versus conservative management for patients with residual stenoses after thrombolytic treatment of myocardial infarction. Treatment of Post-Thrombolytic Stenoses (TOPS) Study Group. AB - BACKGROUND: After thrombolytic therapy for patients with acute myocardial infarction (MI), percutaneous transluminal coronary angioplasty (PTCA) is frequently performed because of the presence of a "significant" infarct vessel stenosis demonstrated at predischarge coronary angiography. Several studies have shown PTCA performed early after thrombolysis to be unnecessary or even harmful. However, PTCA in these trials was generally performed 1-3 days after MI, when the milieu in the infarct artery may be unsuited for PTCA, and the incidence of major ischemic complications was high. To date, no trial has assessed whether delayed PTCA (4-14 days) should be performed in patients without evidence of ischemia on stress testing. METHODS AND RESULTS: To test the hypothesis that delayed PTCA might provide clinical benefit compared with medical therapy alone, 87 patients treated within 6 hours of chest pain onset with thrombolytic therapy and with negative functional test were randomized between PTCA to be performed 4-14 days after MI versus no PTCA. Both groups received medical therapy. Patients with postinfarct angina or prior Q wave infarction in the infarct distribution were excluded. The primary study end point was increase in left ventricular ejection fraction with exercise measured by radionuclide studies 6 weeks after MI, a parameter known from other studies to correlate inversely with future ischemic events. Clinical outcome was also monitored for 12 months. There were no differences between the study groups for any prerandomization variable recorded. Mean age was 57 +/- 10 years, 84% of patients were male, 21% had prior MI, 36% had anterior MI, 7% had multivessel disease, and the infarct stenosis measured 70 +/- 17% before randomization. PTCA was successful in 38 of 42 patients (88%) but resulted in non-Q wave MI due to acute closure of the treated site in three of 42 (9.5%). There was no difference in 6-week resting ejection fraction or increase in ejection fraction with exercise between the two groups (47 +/- 12% and 6 +/- 8%, respectively, in the PTCA group; 49 +/- 10% and 5 +/- 9% in the no-PTCA group; p = NS for both.) There were no deaths in either group. Actuarial 12-month infarct-free survival was 97.8% in the no-PTCA group and 90.5% in the PTCA group (p = 0.07). CONCLUSIONS: There was no functional or clinical benefit from routine late PTCA after MI treated with thrombolytic therapy in this relatively low-risk cohort of patients. These data strongly suggest that patients with an uncomplicated MI after thrombolytic therapy, even if they have a "significant" residual stenosis of the infarct vessel, should be treated medically if they are without evidence of ischemia on stress testing before hospital discharge. PMID- 1423953 TI - Randomized trial of thrombolysis versus heparin in unstable angina. AB - BACKGROUND: The clinical usefulness of intravenous thrombolytic therapy in unstable angina is currently unknown, despite the pathogenetic similarity of this entity to acute myocardial infarction, for which thrombolysis has enjoyed great success. To compare the clinical benefit of intravenous urokinase with that of conventional antithrombotic therapy in preventing the progression of unstable angina to new myocardial infarction, intractable angina, or death within the first 96 hours after hospitalization, 149 patients with unstable angina were randomized to one of two intravenous thrombolytic strategies. METHODS AND RESULTS: Forty-nine patients received 3 million units urokinase i.v. over 90 minutes plus intravenous heparin (group A); 47 patients received unblinded 3 million units urokinase i.v. plus 325 mg aspirin p.o. daily (group B); and 53 patients received placebo thrombolytic infusion plus full-dose heparin (group C). The primary end point of this trial was 96-hour clinical status. There were no significant differences in the baseline characteristics (age, sex, previous myocardial infarction, hypertension prevalence, diabetes, tobacco use, or previous revascularization) among the three groups. Despite an excess of minor untoward reactions for the urokinase groups (chills, 26.5% and 23.4% for groups A and B versus 0% for group C; p < 0.01), there was no significant difference with respect to major bleeds (two, none, and two for groups A, B, and C, respectively; p = NS). At 96 hours after presentation, no significant difference emerged in the incidence of new cardiac events: new myocardial infarctions developed in 10.2% of group A, 6.4% of group B, and 3.8% of group C (p = NS); intractable angina occurred in 6.1% of group A, 10.6% of group B, and 9.4% of group C (p = NS). There were no deaths. All three groups encountered a similar incidence of overall cardiac events: 16.3%, 17.0%, and 13.2% for groups A, B, and C, respectively (p = NS). Although trial enrollment was to extend to 600 patients, interim analysis led to early cessation of enrollment due to a negative trend in respect to outcome after thrombolysis. CONCLUSIONS: High-dose intravenous urokinase followed by either heparin or aspirin can be safely administered to a broad, unselected group of patients with unstable angina. However, this study suggests that no clinical advantage is conferred by urokinase, with either adjunctive antithrombotic therapy over standard heparin therapy alone, when given relatively late (mean, 8.7 hours) after admission for unstable angina. A possible detrimental effect cannot be excluded. PMID- 1423954 TI - A randomized comparison of external and internal cardioversion of chronic atrial fibrillation. AB - BACKGROUND: Delivery of shocks within the right atrium has been reported to be more effective than conventional external shocks in converting atrial fibrillation (AF), but these two cardioversion techniques have never been compared prospectively. The purpose of this study was to compare the efficacies of external and internal cardioversion in patients with chronic AF unresponsive to prior attempts at electrical and/or pharmacological cardioversion. Low-dose amiodarone was used in all patients after cardioversion to suppress recurrences of AF. METHODS AND RESULTS: One hundred twelve patients with AF of at least 1 month in duration were randomly assigned to undergo external cardioversion with 300-360-J shocks or internal cardioversion with 200-300-J shocks delivered through a standard electrode catheter within the right atrium. The patients were treated with amiodarone (200 mg/day 5-7 days/week) for 1 month before electrical cardioversion and afterward if the cardioversion was successful. The patients were evaluated at regular intervals during 1 year of follow-up. The efficacy of internal cardioversion was significantly greater than that of external cardioversion (91% versus 67%, p = 0.002). The only variable that was associated with the outcome of cardioversion was body weight. Among patients in whom sinus rhythm was restored, AF recurred as often after internal and external cardioversion; at 1 year of follow-up, 37% of patients in whom external or internal cardioversion had been effective were still in sinus rhythm. Patients who had undergone an attempt at electrical cardioversion before entry into this study were less likely to remain in sinus rhythm after cardioversion. The only complications of cardioversion were one instance of cerebral thromboembolism after external cardioversion and one instance of transient pulmonary edema after internal cardioversion. Therapy with amiodarone was discontinued because of an adverse drug effect in only three patients. CONCLUSIONS: Internal cardioversion is more effective than external cardioversion in restoring sinus rhythm and is as safe as external cardioversion in patients with chronic AF. The recurrence rate of AF is the same after both types of cardioversion. If conventional electrical cardioversion is ineffective, internal cardioversion should be attempted. The combination of low-dose amiodarone and external or internal cardioversion may result in maintaining sinus rhythm long-term in patients with refractory AF. PMID- 1423956 TI - Dynamic intraventricular obstruction during dobutamine stress echocardiography. A new observation. AB - BACKGROUND: The implications of hypotension occurring during dobutamine stress echocardiography have not been elucidated. We observed in some patients that hyperdynamic left ventricular function developed during dobutamine stress echocardiography and hypothesized that intracavitary obstruction was occurring and might account for hypotension in some patients. METHODS AND RESULTS: Fifty seven consecutive patients undergoing dobutamine stress echocardiography underwent pulsed-wave and continuous-wave Doppler examination of the left ventricular cavity at rest and at peak dobutamine infusion. The development of an intraventricular gradient with dobutamine stress was defined as a late-peaking left ventricular Doppler velocity profile that exceeded basal velocity by at least 1 m/sec. During dobutamine stress testing, left ventricular outflow velocity or intracavitary velocity increased in all patients. Obstruction occurred in 12 patients (21%, group 1). Group 2 was the remaining 45 patients. Peak velocities in group 1 ranged from 2.0 to 5.0 m/sec (mean, 3.5 m/sec), and the mean increase from velocity at rest was 2.3 m/sec. The mean change in systolic blood pressure was significantly lower in patients in group 1 (-15 versus 4 mm Hg, p = 0.02). When the 18 patients with an ischemic response to stress testing (evidenced by new or worsening wall motion abnormalities) were excluded from analysis, systolic blood pressure response was still significantly different for the two groups (-19 versus 2 mm Hg, p = 0.03). CONCLUSIONS: Dynamic left ventricular obstruction is a new observation; it may develop frequently in patients undergoing dobutamine stress echocardiography. Obstruction rather than ischemia may explain a decrease in blood pressure during dobutamine stress echocardiography. PMID- 1423955 TI - Pharmacokinetics and pharmacodynamics of intravenous diltiazem in patients with atrial fibrillation or atrial flutter. AB - BACKGROUND: Diltiazem, a calcium channel blocker, has been shown to be safe and effective in the treatment of patients in atrial fibrillation and/or atrial flutter. However, there have been no pharmacokinetic/pharmacodynamic studies of diltiazem in these patients. METHODS AND RESULTS: The pharmacokinetics and pharmacodynamics of intravenous diltiazem were determined in 32 patients with atrial fibrillation or atrial flutter (mean +/- SD age, 66 +/- 7 years; mean baseline heart rate, 131 +/- 10 beats per minute) after 20 mg or 20 mg followed by 25-mg bolus doses and a 10 and 15 mg/hr infusion for 24 hours. After the 10 and 15 mg/hr infusions of diltiazem, mean +/- SD elimination half-life was 6.8 +/ 1.8 and 6.9 +/- 1.5 hours, volume of distribution was 411 +/- 151.8 and 299 +/- 70.8 I, and systemic clearance was 42 +/- 12.4 and 31 +/- 8.3 l/hr, respectively. Percentages of the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem to diltiazem were < 15% and < 10%, respectively. Thirty of 32 patients maintained response throughout the 24-hour infusion of diltiazem. Using a sigmoidal Emax pharmacodynamic model, a strong relation (mean +/- SD r2, 0.78 +/- 0.2) was observed between plasma diltiazem concentration and percent heart rate reduction. Mean +/- SD Emax (maximum percent reduction in heart rate from baseline) and EC50 (plasma diltiazem concentration that achieves half Emax) were 52 +/- 17% and 110 +/- 84 ng/ml, respectively. The model predicts that mean plasma diltiazem concentration of 79, 172, and 294 ng/ml are required to produce a 20%, 30%, and 40% reduction in heart rate, respectively. A relation between plasma diltiazem concentration and percent change in systolic blood pressure (SBP) or diastolic blood pressure (DBP) from baseline was not observed (mean +/- SD r2, SBP/DBP: 0.35 +/- 0.24/0.36 +/- 0.2). There were no untoward side effects observed. CONCLUSIONS: First, the pharmacokinetics of diltiazem in patients with atrial fibrillation or atrial flutter is nonlinear with an apparent dose-dependent decrease in systemic clearance with increasing infusion rate. Second, using a sigmoidal Emax model, there is a strong relation between plasma diltiazem concentration and percent heart rate reduction. Third, the plasma concentrations of the principal metabolites desacetyldiltiazem and N-desmethyldiltiazem are low and are not expected to contribute significantly to the pharmacodynamics of intravenous diltiazem in these patients. PMID- 1423957 TI - Real-time NMR beam-directed velocity mapping. V-mode NMR. AB - BACKGROUND: Currently available noninvasive techniques for measuring blood flow velocities are constrained by limited view orientations (Doppler ultrasound) or limited time resolution (magnetic resonance imaging, MRI). We describe an MRI technique for measuring flow velocities in real time at arbitrary orientations within a cylindrical volume or "beam": V-mode nuclear magnetic resonance (NMR). METHODS AND RESULTS: The technique was implemented on a standard 1.5-T clinical NMR imager with no special hardware and was tested on phantoms and human volunteers. The beam can be fired at rates up to 60 times per second, allowing measurements on a time scale that is appropriate for ungated cardiac studies. In phantoms, steady flow velocities were measured with the beam aligned along the direction of flow, and the measured velocities correlated well with the actual velocities (r > 0.99). The radial distribution of velocities in phantoms under constant flow conditions was also determined. In humans, flow of blood in the descending aortas of normal and aortic insufficiency subjects was measured. Distinctive backflow of blood because of aortic insufficiency was readily apparent. CONCLUSIONS: The V-mode NMR technique is capable of acquiring clinically relevant real-time blood flow information from any desired angle of view with no attenuation at bone or air-tissue interfaces. PMID- 1423958 TI - Impaired circadian modulation of sympathovagal activity in diabetes. A possible explanation for altered temporal onset of cardiovascular disease. AB - BACKGROUND: Diabetic subjects have a high incidence of cardiovascular accidents, with an altered circadian distribution. Abnormalities in the circadian rhythm of autonomic tone may be responsible for this altered temporal onset of cardiovascular disease. METHODS AND RESULTS: To assess circadian changes of sympathovagal balance in diabetes, we performed 24-hour power spectral analysis of RR interval fluctuations in 54 diabetic subjects (age, 44 +/- 2 years) with either normal autonomic function or mild to severe autonomic neuropathy and in 54 age-matched control subjects. The power in the low-frequency (LF, 0.03-0.15 Hz) and high-frequency (HF, 0.18-0.40 Hz) bands was considered an index of relative sympathetic and vagal activity, respectively. Diabetic subjects with autonomic abnormalities showed a reduction in LF compared with control subjects (5.95 +/- 0.12 In-msec2 versus 6.73 +/- 0.11, p < 0.001) and an even greater reduction in LF, particularly during the night and the first hours after awakening (5.11 +/- 0.18 In-msec2 versus 6.52 +/- 0.14, p < 0.001). Day-night rhythm in sympathovagal balance was reduced or absent in diabetic subjects compared with control subjects. CONCLUSIONS: Diabetic subjects with or without signs of autonomic neuropathy have a decreased vagal activity (and hence a relatively higher sympathetic activity) during night hours and at the same time of the day, during which a higher frequency of cardiovascular accidents has been reported. These observations may provide insight into the increased cardiac risk of diabetic patients, particularly if autonomic neuropathy is present. PMID- 1423960 TI - Radiofrequency catheter ablation of left lateral accessory pathways via the coronary sinus. AB - BACKGROUND: The purpose of this study was to describe a new technique for catheter ablation of left lateral accessory pathways (APs) by radiofrequency energy applied at the epicardium through the coronary sinus wall using a unipolar configuration. METHODS AND RESULTS: In an overall group of 212 patients with left lateral APs, multiple endocardial ablation attempts of the AP were unsuccessful in eight patients. The mean +/- SD cumulative duration of previous attempts was 12 +/- 9 hours, using DC shocks and/or radiofrequency energy applied both at the atrial and/or ventricular AP insertions. Epicardial AP insertion was determined by bipolar and unipolar unfiltered distal electrograms by scanning the coronary sinus with a steerable 6F or 7F catheter with a 4-mm distal electrode. The local atrial to ventricular electrogram amplitude ratio was 0.3-1.6. At the ablation site, the catheter tip was slightly deflected toward the annulus to increase both the ventricular component of electrograms and contact with the epicardium. In four patients, epicardial electrogram timings were earlier than endocardial ones. The AP was ablated in seven of the eight patients with 20-30 W applied for 10-60 seconds. No complications occurred except a marked nonspecific pain during radiofrequency energy application; however, the catheter remained adherent to the coronary sinus wall, and its withdrawal was performed during a new radiofrequency application to decrease the risk of coronary sinus rupture. After ablation, echocardiograms, coronary artery angiograms, and levophase coronary sinus angiograms showed no abnormality in all patients except two who had a probable mural thrombus in the coronary sinus. AP conduction remained abolished for 1-10 months of follow-up in seven patients. CONCLUSIONS: Radiofrequency catheter ablation of left lateral APs can be achieved effectively and relatively safely via the mid or distal coronary sinus when endocardial approaches are unsuccessful. PMID- 1423959 TI - Abnormal neuroendocrine responses during exercise in heart transplant recipients. AB - BACKGROUND: Osmotic and neural factors stimulate neuroendocrine activity during exercise. In contrast to excitatory mechanisms, afferent information from cardiac mechanoreceptors inhibits integrative centers in the hypothalamus and medula oblongata, which serves to buffer neuroendocrine activity. Orthotopic cardiac transplantation results in the loss of afferent information from cardiac mechanoreceptors. Thus, transplantation possibly results in exaggerated neuroendocrine responses when patients are physically active. METHODS AND RESULTS: We measured the neuroendocrine response to moderate and strenuous exercise performed at the same relative intensity in 11 heart transplant recipients (50 +/- 14 years old) 18 +/- 12 months after transplantation and 11 control subjects matched with respect to sex, age, and body size. Plasma levels of norepinephrine, vasopressin, renin activity, atrial natriuretic peptide, angiotensin II, and aldosterone were measured at rest, during a maximal graded exercise test, and during submaximal exercise at 40% and 70% of peak power output on a cycle ergometer (W). Plasma renin activity and atrial natriuretic peptide were elevated at rest in heart transplant recipients (p < or = 0.05). Heart rate (%HRmax reserve), rating of perceived exertion, and reductions in plasma volume (% delta from rest) at the conclusion of the three exercise conditions did not differ between heart transplant recipients and control (p > or = 0.05). Relative changes in neuroendocrine hormones were similar (p > or = 0.05) in heart transplant recipients and control during exercise at 40% of peak power output. Relative changes in plasma norepinephrine, vasopressin, atrial natriuretic peptide, and plasma renin activity were greater (p < or = 0.05) in heart transplant recipients during exercise at 70% of peak power output and the graded exercise test. CONCLUSIONS: We interpret these data as a possible indication of ablation of cardiac mechanoreceptor afferents and unopposed neuroendocrine stimulation in heart transplant recipients. Furthermore, chronic neuroendocrine hyperactivity is likely in ambulatory heart transplant recipients. Although cyclosporine nephrotoxicity is implicated in the development of hypertension, our data suggest that chronic neuroendocrine hyperactivity, which alters renal volume regulation, also contributes to the incidence and severity of hypertension in heart transplant recipients. PMID- 1423961 TI - Temperature monitoring during radiofrequency catheter ablation of accessory pathways. AB - BACKGROUND: Animal studies have suggested that the temperature of the electrode tissue interface during radiofrequency catheter ablation accurately predicts lesion size. The purpose of the current study was to evaluate the utility of continuous temperature monitoring during radiofrequency catheter ablation in patients with Wolff-Parkinson-White syndrome. METHODS AND RESULTS: Twenty patients with manifest preexcitation were included in the study. The ablation catheter was positioned on the ventricular side of the mitral annulus for left sided accessory pathways and on the atrial side of the tricuspid annulus for right-sided and septal accessory pathways. A thermistor imbedded in the distal electrode of the ablation catheter allowed continuous temperature monitoring during each energy application. To define the relation between power and temperature, radiofrequency current was applied several times at each site using outputs of 20, 30, 40, and 50 W. The accessory pathways were successfully ablated in each of the 20 patients. Because of marked variability in the efficiency of heating between sites, power output did not predict temperature. However, at any given site, there was a positive dose-response relation between power and temperature. Radiofrequency energy applications on the atrial side of the tricuspid annulus produced lower temperatures than did applications on the ventricular side of the mitral annulus (49 +/- 7 versus 60 +/- 16 degrees C, p = 0.0001). Transient block in the accessory pathways occurred at a mean of 50 +/- 8 degrees C, whereas permanent block was seen at a mean of 62 +/- 15 degrees C (p = 0.0001). Less than half of the applications at outputs < or = 40 W produced temperatures adequate to interrupt accessory pathway conduction. An abrupt rise in impedance caused by coagulum formation occurred only at temperatures between 95 and 100 degrees C. CONCLUSIONS: Temperature monitoring may facilitate radiofrequency catheter ablation of accessory pathways. By adjusting power output to ensure that adequate but not excessive temperatures have been achieved, a rise in impedance can be avoided and the total number of energy applications and procedure duration may be reduced. PMID- 1423962 TI - Identification of patients with coronary disease at high risk for loss of employment. A prospective validation study. AB - BACKGROUND: Work disability is common in patients with coronary artery disease and adversely affects both economic well-being and quality of life. The purpose of this study was to construct a model to predict premature departure from the work force of patients with coronary disease and to validate this model prospectively in an independent cohort of patients. METHODS AND RESULTS: We enrolled 1,252 coronary disease patients referred for diagnostic cardiac catheterization who were less than age 65, employed, and without prior coronary angioplasty or coronary bypass surgery. Medical, functional, psychological, economic, and job-related variables were measured at the time of baseline diagnostic cardiac catheterization, and all patients were followed for 1 year. Three hundred twelve patients underwent percutaneous transluminal coronary angioplasty (PTCA) within 60 days of catheterization, and 449 had coronary artery bypass graft surgery (CABG) within 60 days of catheterization. The remaining 491 patients were treated with initial medical therapy. Logistic regression was used to develop a multivariable model for predicting 1-year work status in the training sample patients (872 patients enrolled between March 1986 and February 1989). This model was then validated in the independent prospective test sample (380 patients enrolled between March 1989 and June 1990). Eight factors were independent predictors of departure from the work force: lower initial functional status (as assessed by the Duke Activity Status Index), followed by older age, black race, presence of congestive heart failure, lower education level, presence of extracardiac vascular disease, poorer psychological status, and lower job classification. Standard clinical variables provided only 20% of the total predictive information available from the model about follow-up work outcomes, whereas functional measures provided 27%, and demographic and socioeconomic measures provided 45%. In the test sample, the area under the receiver operating characteristic curve for the model predictions was 0.74, compared with 0.80 in the training sample, and model predictions agreed well with observed prevalences of return to work. After adjustment for baseline imbalances, there was no significant difference in 1-year return-to-work rates among the patients receiving initial PTCA or CABG therapy versus initial medical therapy. CONCLUSIONS: Patients with coronary disease who are at high risk for premature departure from the work force can be accurately identified from a combination of medical and nonmedical risk factors. The model developed in this study provides a tool to identify patients at high risk for premature loss from the work force. Such patients may benefit from special multidimensional intervention programs designed to preserve work status. Our data show that revascularization with either PTCA or CABG is not, by itself, sufficient to accomplish this goal. PMID- 1423963 TI - Tobacco use and urinary excretion of thromboxane A2 and prostacyclin metabolites in women stratified by age. AB - BACKGROUND: Activated platelets have been implicated in both acute thrombus formation and atherogenesis. Because smoking is a risk factor for cardiovascular disease in men and women and male smokers have biochemical evidence of increased platelet activation, we found it of interest to study whether smoking augments platelet activity in women as well. METHODS AND RESULTS: Data on smoking habits and a urinary sample were obtained from 125 healthy female nonsmokers and an equal number of smokers, stratified by age in five groups from 18 to 59 years old. Urinary samples were analyzed with gas chromatography/mass spectrometry for the 2,3-dinormetabolites of thromboxane A2 (Tx-M), reflecting platelet activity, and prostacyclin (PGI-M), representing platelet/vessel wall interaction. Urinary Tx-M in smokers was higher than in nonsmokers (p < 0.001), increasing with the number of cigarettes smoked per day and with age. In nonsmokers, there was no difference in Tx-M between the age groups. Urinary PGI-M in smokers was higher than that in nonsmokers (p < 0.001) and decreased with age in nonsmokers but not in smokers. There was no difference in Tx-M between previous smokers and lifelong nonsmokers. CONCLUSIONS: The elevated Tx-M in women who smoke cigarettes indicates an increased platelet activity that is dependent on smoking intensity. In parallel, PGI-M is augmented, suggesting that platelet/vessel wall interaction is stimulated. Quitting smoking is an effective means to restore platelet function. We propose that the observed increase in platelet activity in women who smoke cigarettes may be related to subsequent development of cardiovascular disease and that quitting smoking should be considered a high-priority medical target also in this sex. PMID- 1423964 TI - Clinical outcomes after the arterial switch operation for transposition. Patient, support, procedural, and institutional risk factors. Congenital Heart Surgeons Society. AB - BACKGROUND: As the probability increases that the arterial switch operation is optimal treatment for transposition, detailed information about outcomes and the circumstances in which they are suboptimal becomes important. METHODS AND RESULTS: A multi-institutional prospective study with annual detailed follow-up included 513 neonates with simple transposition or transposition and ventricular septal defect entering for diagnosis and treatment at < 15 days of age and undergoing an arterial switch repair. The 1-month and 1- and 5-year survivals were 84%, 82%, and 82%, respectively. The hazard function for death had a rapidly declining single phase that approached zero by 12 months after surgery. Among the eight patients who died > or = 3 months after the operation, four had severe ventricular dysfunction, probably related to imperfect coronary arterial transfer. Coexisting single ventricular septal defect was not a risk factor for death. Origin of the left main coronary artery or only the left anterior descending or the circumflex artery from the right posterior sinus (sinus 2) was a risk factor that was even stronger when an intramural course was present; multiplicity of ventricular septal defects was a risk factor. Longer global myocardial ischemic time and total circulatory arrest time were risk factors. Certain institutions were shown to be risk factors for death; the results in some improved with increasing experience, in some they did not, and in some they worsened. CONCLUSIONS: Good early and intermediate-term clinical outcomes can be obtained in neonates with simple transposition and transposition and ventricular septal defect by use of the arterial switch operation. Certain coronary artery patterns and certain institutions lessen the goodness of outcome. PMID- 1423965 TI - Diagnosis and management of right ventricle-dependent coronary circulation in pulmonary atresia with intact ventricular septum. AB - BACKGROUND: Coronary artery anomalies including 1) right ventricle (RV)-to coronary artery fistulas, 2) coronary artery stenoses, and 3) coronary occlusions occur in patients with pulmonary atresia with intact ventricular septum (PA-IVS). In some, a large part of the coronary blood supply may depend on the RV. This RV dependent coronary circulation may determine survival after right ventricular decompression (RVD): RVD may cause RV "steal" in the presence of fistulas alone and ischemia, coronary isolation, or myocardial infarction in the presence of coronary stenoses. METHODS AND RESULTS: Eighty-two patients with PA-IVS who presented between January 1979 and January 1990 were reviewed; 26 (32%) had RV-to coronary artery fistulas. Of these 26, 23 had adequate preoperative coronary angiograms for analysis. RVD was achieved in 16. Seven of 16 had fistulas only; each survived RVD. Six of 16 had stenosis of a single coronary artery [left anterior descending coronary artery (LAD), four; right coronary artery (RCA), two]; four of six survived RVD. Three of 16 had stenoses and/or occlusion of both the RCA and LAD; all three died shortly after RVD of acute left ventricular dysfunction. CONCLUSIONS: 1) Potential RV steal alone does not preclude successful RVD. 2) Fistulas with stenoses to a single coronary artery may not preclude successful RVD. 3) RVD appears to be contraindicated in the presence of stenoses and/or occlusion involving both the right and left coronary systems. Nonsurvival after RVD seems to depend on the amount of the left ventricular myocardium at risk, i.e., that which is distal to coronary artery stenoses, especially when involvement of both coronary arteries limits effective collateralization. Precise definition of coronary arterial anatomy is mandatory in neonates with PA-IVS. PMID- 1423966 TI - Dehydroepiandrosterone sulfate, incidence of myocardial infarction, and extent of atherosclerosis in men. AB - BACKGROUND: Antiatherogenic effects of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) have been suspected for more than 30 years, yet the available evidence to support or refute such effects in humans is inconclusive. The hypothesis has not been adequately tested in large-scale epidemiological studies. METHODS AND RESULTS: The present study used a cohort of men initially free of clinically detectable coronary heart disease, stroke, and cancer to compare DHEAS levels measured in sera obtained in 1968-1971 between 238 cases who had definite coronary heart disease during the subsequent 18 years and 476 age-matched controls who survived the follow-up period and remained free of clinically detectable coronary heart disease. In a separate study, the relation of DHEAS levels to extent of atherosclerosis was examined among 82 cohort men who died during the follow-up period and had protocol autopsies. Age-adjusted DHEAS levels were lower among fatal cases of coronary heart disease than among controls (94.7 versus 106.9 micrograms/dl, respectively; p < 0.05). After adjustment for eight coronary risk factors, the odds ratio for fatal coronary heart disease comparing a 100-micrograms/dl difference in DHEAS level was 0.46 (95% confidence intervals, 0.19-1.07). In contrast, age-adjusted DHEAS levels did not significantly differ between nonfatal cases of myocardial infarction and controls (107.2 versus 106.9 micrograms/dl, respectively). Furthermore, DHEAS levels were not related to extent of atherosclerosis at autopsy. CONCLUSIONS: These findings do not support a role of DHEAS in the development of nonfatal myocardial infarction or the progression of atherosclerosis. The association of DHEAS with fatal coronary heart disease and possibly with death from all causes merits further investigation. These findings suggest continued skepticism that DHEAS has an important role in coronary disease etiology or prevention. PMID- 1423967 TI - Effect of chronic subcutaneous or intramural administration of heparin on femoral artery restenosis after balloon angioplasty in hypercholesterolemic rabbits. A quantitative angiographic and histopathological study. AB - BACKGROUND: Heparin is known to have antithrombotic, anticoagulant, and antiproliferative effects. We hypothesized that chronic subcutaneous and/or direct intramural administration of heparin would reduce restenosis and inhibit plaque growth after balloon angioplasty. METHODS AND RESULTS: Focal atherosclerosis was induced bilaterally in the femoral arteries of 59 rabbits by air desiccation intimal injury and a 2% cholesterol diet. After angioplasty, the rabbits were assigned to one of four treatment groups. Control arteries (n = 21) received no additional heparin. A second group of 20 arteries was treated with a porous balloon that delivered heparin (1,500 units) directly into the arterial wall. A third group (n = 29) received subcutaneous heparin (350 units.kg-1.day-1) for 28 days, and a fourth group (n = 23) was treated with subcutaneous and intramural heparin. Quantitative angiography showed a modest reduction in restenosis (defined as the change in minimal luminal diameter from immediately after angioplasty to 28 days) with subcutaneous heparin compared with control arteries (0.32 +/- 0.18 versus 0.58 +/- 0.34 mm, p < 0.01); however, luminal diameter was not improved at 28 days compared with before angioplasty. Intramural delivery of heparin by the porous balloon catheter was confirmed by use of fluoresceinated heparin in one animal. Angiographic restenosis was not reduced in arteries treated with intramural heparin versus controls (0.61 +/- 0.54 versus 0.58 +/- 0.34 mm, p = NS). Blinded planimetric analysis of histological sections showed no differences in luminal cross-sectional area narrowing by atherosclerotic plaque, in plaque area, or in plaque/media ratio at 28 days among the four treatment groups. CONCLUSIONS: Chronic subcutaneous heparin after balloon angioplasty results in a modest reduction in angiographic restenosis in this model; however, the absolute luminal diameter is not improved compared with before angioplasty, and plaque area and percent luminal narrowing by plaque were not different among the four treatment groups. Heparin can be delivered into an atherosclerotic plaque by a porous balloon, but this treatment does not reduce restenosis after angioplasty in this model. PMID- 1423968 TI - Spatial and temporal linking of epicardial activation directions during ventricular fibrillation in dogs. Evidence for underlying organization. AB - BACKGROUND: It remains controversial as to whether electrical activation during ventricular fibrillation (VF) is organized. To detect the presence of organization in VF, the direction of epicardial activation (EA) at multiple sites was examined by using vector mapping. If VF is not a random process, EA direction at a given site should be related to adjacent sites and prior beats. METHODS AND RESULTS: Thirteen dogs with healing myocardial infarction (MI) and four dogs without MI had VF induced by programmed stimulation. Using a plaque electrode array with a 2.5-mm interelectrode distance, 91 vector loops were created for each "beat" of VF. Direction of maximum EA was determined at each site for the first 10 consecutive beats of VF and for 10 consecutive beats recorded 5 seconds after VF was established. Spatial and temporal linking of EA directions was evaluated by the ability of activation direction at a given site to be predicted by activation directions at eight adjacent sites for the index beat and at eight adjacent sites and the site of interest for the preceding beat using stepwise linear regression. The strength of the model as reflected by the correlation coefficient (r) indicated the degree of linking. We determined 1) changes in the degree of linking over time during a given episode of VF (using a paired difference t test), 2) differences in the degree of linking between the anterior and posterolateral walls in animals with (n = 4) and without (n = 4) MI (using two-way ANOVA), and 3) the effect of repeated inductions (n = 10) on the degree of linking (using one-way ANOVA with repeated measures). During 57 episodes of VF, r for each model ranged from 0.64 to 0.88 during the transition to VF to 0.39 0.78 during established VF (p < 0.0001 for the difference). The presence of MI, the site of recording, and repeated inductions did not affect the degree of linking. For each episode, spatial linking was more prominent than temporal linking. CONCLUSIONS: Electrical activation during VF is organized. The degree of linking of EA directions during VF is not affected by the presence of MI, the site of recording, or repeated inductions of VF. During the first 5 seconds of VF, the degree of linking decreases. PMID- 1423969 TI - Serotonin selectively aggravates subendocardial ischemia distal to a coronary artery stenosis during exercise. AB - BACKGROUND: The coronary circulation has been shown to remain responsive to vasodilator and vasoconstrictor stimuli during myocardial ischemia. Because serotonin possesses both vasodilator and vasoconstrictor properties, we examined its effect in the coronary circulation distal to an arterial stenosis that resulted in myocardial hypoperfusion during exercise. METHODS AND RESULTS: Seven chronically instrumented dogs were studied during treadmill exercise in the presence of a stenosis that reduced distal left circumflex coronary artery perfusion pressure to 42 +/- 1 mm Hg. Myocardial blood flow was assessed with radioactive microspheres during exercise before and during intracoronary infusion of 0.4 and 2.0 micrograms/kg-1.min-1 serotonin. The stenosis was adjusted to maintain distal coronary pressure constant during control exercise and with the two doses of serotonin. In seven dogs, the effect of serotonin (2.0 micrograms/kg 1.min-1) was also studied during exercise with normal arterial inflow. During control exercise, the stenosis decreased mean myocardial blood flow to 45% of flow in the normally perfused region. This decrease was most pronounced in the subendocardium (endocardial/epicardial ratio 0.36 +/- 0.06 versus 1.46 +/- 0.14 in the control region; p < 0.01). With no change in pressure distal to the stenosis, serotonin decreased subendocardial flow from 0.51 +/- 0.09 ml/min-1.g-1 to 0.41 +/- 0.12 (p < 0.05) and then to 0.35 +/- 0.08 ml/min-1.g-1 (p < 0.05) and tended to increase subepicardial flow from 1.47 +/- 0.17 to 1.91 +/- 0.23 and 1.85 +/- 0.21 ml/min-1.g-1 (p = 0.08) during infusions of 0.5 and 2.0 micrograms/kg-1.min-1, respectively, with no change in total arterial inflow. In contrast, in the absence of a stenosis, serotonin (2.0 micrograms/kg-1.min-1) increased subendocardial flow from 2.43 +/- 0.25 to 3.73 +/- 0.25 ml/min-1.g-1 (p < 0.01) and subepicardial flow from 1.88 +/- 0.20 to 5.29 +/- 0.38 ml/min-1.g-1 (p < 0.01). CONCLUSIONS: During normal arterial inflow, serotonin dilated coronary resistance vessels and increased flow to all myocardial layers. During hypoperfusion, a vasodilator response was still present in the subepicardium, but vasoconstriction was then observed in the subendocardium. Our data suggest that serotonin constricts the intramural penetrating arteries, thereby selectively increasing resistance to subendocardial blood flow. PMID- 1423970 TI - Vascular injury and time course of smooth muscle cell proliferation after experimental holmium laser angioplasty. AB - BACKGROUND: In vitro experiments have shown that holmium laser energy can effectively ablate even calcified plaque in human arterial vessels. Because high energy densities from holmium lasers can easily be transmitted through quartz fibers, this solid-state laser has been suggested as an alternative intraluminal treatment of atherosclerotic plaque. METHODS AND RESULTS: To develop an intimal plaque, 35 New Zealand White rabbits underwent electrical stimulation of their right carotid artery for 28 days. Subsequently, in 25 rabbits, holmium laser angioplasty (wavelength, 2.12 microns; pulse duration, 150 microseconds; energy density, 350 mJ/mm2) was performed. To study the morphological results, the vessels were excised after 7, 14, 28, and 42 days. Cross sections were analyzed in regard to laser-specific injury. Staining of alpha-actin was used to identify smooth muscle cells (SMCs). After bromodeoxyuridine labeling, the extent of proliferation (number of cells undergoing DNA synthesis) was determined by using a monoclonal antibody. Holmium laser ablation resulted in an initial decrease of the numbers of intimal cell layers in the early group (7 days after treatment: 5 +/- 1 cell layers with 76 +/- 39 microns; control: 13 +/- 3 cell layers with 144 +/- 44 microns). Quantification of SMCs undergoing DNA synthesis in the intima (control: 51 +/- 19 cells/mm2) showed a significant increase of labeled cells after 7 (216 +/- 74 cells/mm2, p = 0.003) and 14 days (281 +/- 139 cells/mm2, p = 0.011). Integrity of the internal elastic lamina was disrupted in all animals after intervention. Seven and 14 days after treatment, a considerable reduction of medial cell nuclei was found in 10 of 12 animals. SMC proliferation in the medial layer was increased within the first 2 weeks after laser ablation (168 +/- 113 cells/mm2; control: 8 +/- 4 cells/mm2; p = 0.023). Six weeks after holmium laser angioplasty, SMC proliferation had returned to control levels in the intima and remained increased in the medial layer. This proliferative response resulted in a significant increase of intimal thickening within 6 weeks after laser ablation (30 +/- 6 cell layers, 375 +/- 97 microns resp.; p = 0.001 each). CONCLUSIONS: Holmium laser treatment leads to considerable vessel wall injury and results in SMC proliferation in the intimal and medial layer with a maximum of proliferative activity within the first 2 weeks. Subsequently, this results in considerable intimal and medial hyperplasia within 6 weeks after treatment. PMID- 1423971 TI - Percutaneous polymeric stents in porcine coronary arteries. Initial experience with polyethylene terephthalate stents. AB - BACKGROUND: To test the feasibility of percutaneous deployment of intracoronary polymeric stents, a prototype polyethylene terephthalate (PET) stent and a catheter-based delivery system were developed. METHODS AND RESULTS: Polymeric stents were deployed in the coronary arteries of 11 Yucatan swine: six stents were placed in the left anterior descending coronary artery, four stents were placed in the circumflex artery, and one stent was placed in the right coronary artery. Stent deployment was achieved by withdrawal of an outer delivery sheath, thus allowing the PET stent to self-expand to a preformed configuration. Two animals died during surgery, one during stent placement and the other several hours after implantation due to intracoronary thrombus formation. Two animals were electively sacrificed within 24 hours of stent implant to examine the adequacy of stent deployment within the coronary vessel. The remaining seven animals survived until the termination of the study 4-6 weeks later. Light microscopic examination of the stented vessels showed an extensive neointimal proliferative response with vessel occlusion in all animals who survived initial stent placement. There were two distinct types of histological responses to the PET stent--a chronic foreign body inflammatory response around the stent tines and a neointimal proliferative response in the center of the occluded vessel lumen. The histological response seen in the central area of the vessel was morphologically similar to that seen in patients with restenosis after successful percutaneous transluminal coronary angioplasty, whereas the morphological response seen at the periphery of the stent tine was similar to that exhibited by a chronic foreign body reaction and was not typical of that seen in a restenosis lesion. A ventricular aneurysm also developed in the area of myocardium that was previously supplied by the occluded vessel. CONCLUSIONS: This study demonstrates that percutaneous deployment of polymeric stents in the coronary arteries is technically feasible. The use of PET polymer was associated with an intense proliferative neointimal response that resulted in complete vessel occlusion. Histological examination of the stented segments of the vessel revealed no evidence that dissection of the vessel wall had occurred at the time of initial stent deployment. Although the PET polymer was of similar quality to that used in the manufacture of balloon angioplasty catheters, a toxic chemical or contaminant effect cannot be completely excluded as the stimulus to intimal proliferation. This finding may have relevance to the selection of materials for use as intravascular devices. PMID- 1423972 TI - Changes in pericardial pressure during the perinatal period. AB - BACKGROUND: To determine how the tissues that surround the heart affect diastolic and systolic function during the perinatal period, we studied the pressure diameter relation of the left ventricle in partially delivered fetal lambs. METHODS AND RESULTS: We anesthetized (1.5-2.0% halothane, balance O2) and ventilated six pregnant ewes (142-144 days of gestation) and then partially delivered each lamb by cesarean section. Each lamb was instrumented to record left ventricular anteroposterior diameters (endocardial ultrasonic transducers), pericardial pressure (liquid-containing balloon), and left ventricular pressure (transducer-tipped catheter). Left ventricular pressure-diameter relations were recorded under three conditions: initially, with a closed chest and closed pericardium (before ventilation); second, after interruption of the umbilical circulation and 1 hour of ventilation; and finally, when the lungs and the pericardium were retracted from the heart. Pericardial pressure (recorded at a common diameter, i.e., the maximal end-diastolic diameter recorded before ventilation) decreased by 48% after 1 hour of ventilation (p < 0.05). After ventilation, left ventricular anteroposterior diameters were 4-5% greater (p < 0.05) at each end-diastolic pressure compared (12.5, 15.0, 17.5, and 20 mm Hg). Thus, ventilation appeared to increase left ventricular diastolic compliance. Contractility also appeared to increase after ventilation when evaluated using ventricular stroke work as a function of end-diastolic pressure as preload. When we used a more appropriate measure of preload (i.e., transmural end-diastolic pressure), ventilation did not change left ventricular diastolic compliance or contractility. Thus, left ventricular systolic function increased because of an increase in preload. CONCLUSIONS: The tissues surrounding the fetal heart significantly augment pericardial pressure and limit left ventricular preload. The initiation of ventilation reduces pericardial pressure, increases left ventricular preload, and increases left ventricular systolic function. At birth, a decrease in pericardial pressure and the resulting increase in preload may help increase left ventricular output through the Frank-Starling mechanism. PMID- 1423973 TI - Assignment of patients into the classification of cardiomyopathies. AB - The original classifications of the cardiomyopathies based on anatomic criteria from radiographic and necropsy studies, as well as hemodynamic criteria from clinical and catheterization data, have been supplemented in recent years by information from noninvasive techniques. Echocardiography, radionuclide methods, and ambulatory ECG, in particular, have facilitated the ethical screening of family members and those less symptomatic than patients on whom the original classification was based. These powerful methods show a broad spectrum of anatomy and ventricular physiology along the natural history of and within the traditional categories of the cardiomyopathies. They also provide data on the effect of ventricular loading conditions affecting a range of diastolic filling patterns. This review has attempted to point out the areas of overlap among and/or controversy about the categories that have led us to a feeling of frustration when trying to neatly classify individual patients. The addition of filling patterns from Doppler echocardiography and nuclear angiography to the standard methods has been reviewed and hopefully will lend more perspective to the range of physiology seen in these conditions. The categories of cardiomyopathy should not be seen as excluding patients with the newly recognized variations in anatomy and ventricular filling patterns. Rather, the classification provides a framework on which to build and expand our understanding of these important conditions. PMID- 1423974 TI - Ensuring automatic detection of ventricular fibrillation. PMID- 1423975 TI - Subcutaneous heparin during coronary thrombolysis. Too little, too late. PMID- 1423976 TI - Conjunctive heparin therapy. Limitations of subcutaneous administration. PMID- 1423977 TI - Is thrombolytic therapy striking out in unstable angina? PMID- 1423978 TI - Temperature response in radiofrequency catheter ablation. PMID- 1423980 TI - Heparin. Will it control intimal thickening after angioplasty? PMID- 1423979 TI - Evolution of therapy for D-transposition of the great arteries. PMID- 1423981 TI - Anitschkow cells in experimental autoimmune myocarditis. PMID- 1423982 TI - Defibrillators and ventricular dysfunction. PMID- 1423983 TI - Plasminogen activator inhibitor-1 plasma levels and coronary restenosis. PMID- 1423984 TI - Statement on smoking and cardiovascular disease for health care professionals. American Heart Association. PMID- 1423985 TI - Outcome of Stanford type B acute aortic dissection. AB - BACKGROUND: The optimal timing of surgery in patients with Stanford type B aortic dissection remains controversial. This report reviews retrospectively early and long-term outcomes of patients with Stanford type B acute aortic dissections at our institute. METHODS AND RESULTS: From April 1979 through January 1991, 75 patients were diagnosed with Stanford type B aortic dissection, and 58 of them were hospitalized within 2 weeks from onset. They were treated initially as follows: emergent surgery was performed in 13 patients for rupture or impending rupture, and the remaining 45 were treated medically. In the former group, nine patients (69%) died; in the latter, eight (18%) needed surgery because of enlargement or rupture of the aneurysm in the follow-up period, and only one of these (13%) died. Of the other 37 patients treated medically, three (8%) died within 2 weeks and seven died (19%) in the chronic phase, four of them from rupture. Among 42 discharged patients initially treated medically, rupture occurred in 11.9% (five of 42). CONCLUSIONS: In acute-phase cases, surgical mortality is so high that medical treatment is preferable unless there are major complications. However, even in patients who had undergone successful initial medical treatment, expansion of the aneurysm, requiring surgery, often occurred. If careful observation reveals any sign of expansion, because elective surgery can be performed at low risk, it should be considered as soon as possible before a rupture develops. PMID- 1423986 TI - Modified Fontan procedure in patients less than 4 years of age. AB - BACKGROUND: Initial experience with the modified Fontan procedure in patients < 4 years of age has met with variable success, with early reports showing a high mortality. More recently, improved results with the modified Fontan procedure in younger patients have been achieved. Important advantages of an early Fontan include protection of the pulmonary vascular bed and preservation of ventricular function by reduction in ventricular volume overload and chronic hypoxemia. METHODS AND RESULTS: From 1982 through May 1991, 90 patients < 4 years of age underwent a modified Fontan procedure. The average age was 29 months (range, 7-48 months), and 30 patients were < 2 years of age. Diagnoses included tricuspid atresia in 36, single ventricle in 45, pulmonary atresia intact septum in seven, and hypoplastic left heart syndrome in two patients. An adjustable ASD was placed in 21. Early mortality was 8.9% (eight of 90), which is only slightly higher than our overall Fontan early mortality of 7.4% in 242 patients. The early mortality in the 30 patients < 2 years of age was 6.7% (two of 30). In a mean follow-up of 38 months (range, 7-89 months), there have been three late deaths (3.7%), and one patient has undergone cardiac transplantation. CONCLUSIONS: Early Fontan should be undertaken in patients > 6 months old who present with increasing cyanosis provided good hemodynamics are present. A modified Fontan procedure can be performed safely with good clinical results in patients < 4 years old. PMID- 1423987 TI - Late functional status of survivors of the Fontan procedure performed during the 1970s. AB - BACKGROUND: During the 1970s (1973-1979), 41 patients with tricuspid atresia and 25 patients with double-inlet left ventricle had a Fontan procedure performed at the Mayo Clinic. In the tricuspid atresia group, there were seven hospital deaths and six late deaths, leaving 28 survivors 11-16 years after surgery. In the double-inlet left ventricle group, there were six hospital deaths and six late deaths, leaving 13 survivors 11-13 years after surgery. METHODS AND RESULTS: The present status of 38 of the 41 long-term survivors was recently (September 1990) determined. Of these 38 patients contacted, 34 felt they were in excellent or good condition, three considered themselves in fair condition, and one was in poor condition. Nineteen of the 38 (50%) were receiving no cardiovascular medications. Twenty-eight (76%) were employed full-time or were full-time students with three others working part-time. Only four patients (11%) felt physically incapable of working or attending school. Seven patients have graduated from college since their Fontan procedure with three others presently enrolled. Present occupations include architect, lawyer, industrial manager with a master's degree, policeman, truck driver, horseback riding instructor, and artist. Nine patients are married, and one woman tolerated a pregnancy without difficulty. The most troublesome late problems requiring medical therapy were atrial dysrhythmia in seven patients (18%) and protein-losing enteropathy in two patients (5%). CONCLUSIONS: Surgical mortality of the Fontan procedure for tricuspid atresia and double-inlet left ventricle is now less than 10%, and that, plus these late results, justify continued application of this operation in patients with these lesions. PMID- 1423988 TI - Total extracardiac right heart bypass. AB - BACKGROUND: Total cavopulmonary connection has been proposed as a rational alternative to atriopulmonary connection for complex Fontan operations. In addition to fluid dynamic advantages proposed by de Leval, total right heart bypass may address an emerging important issue after repair of single ventricle: late atrial arrhythmias. The purpose of this study is to document the postoperative hemodynamic findings in 22 consecutive patients who received a total extracardiac right heart bypass with an inferior vena cava-to-pulmonary artery extracardiac Dacron conduit with a modified Glenn anastomosis (superior vena cava-to-pulmonary artery anastomosis). METHODS AND RESULTS: Twenty-eight patients with complex congenital heart disease underwent this surgical procedure. One patient died (early mortality, 3.5%). Mean follow-up was 13.9 months. Postoperative cardiac catheterization and echo Doppler studies were performed in 22 of the 27 survivors. In 18 of 22 patients, hemodynamic data were satisfactory; a preferential direction of caval flows to both lungs was observed. Echo Doppler assessments show that forward cavopulmonary flow appears as a predominant early diastolic event, in contrast to what occurs in atriopulmonary connections. This hemodynamic model emphasizes the possible role of the diastolic ventricular performance (as a "suction pump") in Fontan circulation. Early postoperative atrial arrhythmias were observed in two of the survivors. CONCLUSIONS: The technical advantages and the hemodynamic benefits of this form of right heart bypass are encouraging. Although the use of artificial material in this procedure is extensive, none of the survivors showed thromboembolic complications or peel formations with narrowing and/or obstruction. Further investigations during a longer follow-up are needed to confirm the early and intermediate results, especially the reduction of late atrial arrhythmias. PMID- 1423989 TI - Factors associated with choreoathetosis after cardiopulmonary bypass in children with congenital heart disease. AB - BACKGROUND: Choreoathetosis (CHO) after congenital heart surgery has been described since 1960. Risk factors and patient outcome have not been well defined. METHODS AND RESULTS: As our complexity of cases increased and management of pH on cardiopulmonary bypass (CPB) evolved, we noted the appearance of CHO among patients beginning in 1986. We reviewed the hospital course and follow-up of all 19 affected children, including eight younger patients (median age, 4.3 months) who developed a mild transient form of CHO, all of whom survived and had complete resolution of CHO; seven of these eight patients had deep hypothermic circulatory arrest (DHCA). Eleven older patients (median age, 16.8 months) developed severe persistent CHO; 11 had DHCA, 10 were cyanotic, seven had anatomic pulmonary atresia, and three others were physiologically analogous with a systemic to pulmonary artery shunt-dependent circulation. Five of six patients who had pertinent preoperative angiography had systemic to pulmonary collateral vessels arising from the head and neck arteries. Mortality in severe patients was 36% (four of 11); the seven survivors showed improvement, but only one had a normal neurological examination after 60 months of follow-up. When severe CHO patients were compared with 17 age- and diagnosis-matched patients without neurological complications, no differences were found in CPB or DHCA times, arterial blood gases, or hematocrits. Time from onset of CPB to onset of DHCA (time to shutoff) was shorter in the severe persistent CHO group than for comparison patients (22 +/- 7 versus 40 +/- 29 minutes, p = 0.053). CONCLUSIONS: Factors that may be associated with the development of severe persistent CHO include 1) age beyond early infancy, 2) cyanotic heart disease with systemic to pulmonary collaterals, particularly those arising from the head and neck vessels, and 3) the duration of the cooling period used in conjunction with deep hypothermic circulatory arrest. We advocate earlier reparative surgery, precise preoperative diagnosis and preoperative or intraoperative control of systemic to pulmonary artery collaterals, and further study of pH effects during CPB on development of CHO. PMID- 1423990 TI - High-frequency jet ventilation for respiratory failure after congenital heart surgery. AB - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is considered when respiratory failure (RF) persists despite increasing conventional mechanical ventilation (CMV). High-frequency jet ventilation (HFJV) can improve ventilation with comparable mean airway pressure (PAW) to that found on CMV. This study was undertaken to determine whether HFJV is an effective treatment and alternative to ECMO for RF after congenital heart surgery. METHODS AND RESULTS: HFJV was instituted in nine patients ranging in age from 6 days to 3.3 years with congenital heart disease meeting pulmonary criteria for ECMO. Indications for HFJV were pulmonary hypertension (six), adult-type respiratory distress syndrome (two), and pneumonitis (one). Seven patients (77%) were placed on HFJV within 24 hours of operation, and two patients required HFJV 2 weeks after operation. HFJV resulted in resolution of RF in eight of nine patients (89%). After 1 hour of HFJV, the arterial pH increased from 7.40 +/- 0.1 to 7.56 +/- 0.1 (p < 0.05) and the PaCO2 decreased from 44 +/- 15 to 29 +/- 12 mm Hg (p < 0.05). During HFJV there was no change in PaO2, although the FIO2 decreased from 0.99 +/- 0.0 to 0.73 +/- 0.2 (p < 0.05). There was no change in PAW, peak inspiratory pressures, positive end-expiratory pressures, heart rate, or mean arterial blood pressure during HFJV when compared with CMV. Mean duration of HFJV was 43 hours. Four patients were extubated and discharged from the hospital. Two patients were extubated but died from sepsis. Two patients had resolution of RF, but one died at reoperation and one from multisystem organ failure. The patient who failed HFJV therapy was placed on ECMO and died. CONCLUSIONS: This study suggests that HFJV improves ventilation and is an alternative to ECMO in patients with RF after surgery for congenital heart disease. PMID- 1423991 TI - Surgical management of late right ventricular failure after Mustard or Senning repair. AB - BACKGROUND: Information on surgical management and outcome in patients who develop symptomatic right ventricular failure after prior Mustard or Senning operations is limited. METHODS AND RESULTS: From March 1987 to March 1991, 10 patients 3.6-23.5 years old (median, 7.0 years) with transposition of the great arteries and prior Mustard (six patients) or Senning (four patients) repairs (performed at ages 2 months to 5 years; median, 6 months) underwent surgical intervention for symptomatic right ventricular failure. In five of 10 patients, anatomic correction with either an arterial switch operation (three patients) or a pulmonary artery-to-aorta anastomosis and right ventricle-to-pulmonary artery conduit (two patients) was performed. Before anatomic correction in these five patients, four of five patients had a pulmonary artery band to prepare the left ventricle. The interval between preparation and correction ranged from 8 days to 12 months (median, 2 months). One patient died after an arterial switch operation. In the remaining five patients, coexisting left ventricular dysfunction precluded anatomic correction; all five patients survived cardiac transplantation. Survival for the entire group of 10 patients is 90%, and the median postoperative hospital stay was 17 days. During follow-up (12-62 months; median, 27 months), there were no deaths. Neoaortic insufficiency after anatomic correction was common (mild in one patient, moderate in two patients, and severe in one patient who required aortic valve replacement 4 months after surgery). In the transplantation group, one patient developed lymphoma 3 months after transplantation but is currently in remission after reduction of immunosuppression. CONCLUSIONS: In patients who develop late right ventricular failure after Mustard or Senning repair, surgical intervention with either anatomic correction or cardiac transplantation can be done with acceptable morbidity and low mortality. Neoaortic valve insufficiency demands close follow up after anatomic correction. PMID- 1423992 TI - Failure of cryopreserved homograft valved conduits in the pulmonary circulation. AB - BACKGROUND: This study evaluates our experience with the cryopreserved homograft valved conduit used for reconstruction of the pulmonary circulation in patients with congenital heart disease. METHODS AND RESULTS: Between July 1, 1985, and December 31, 1990, 219 patients had cryopreserved homograft extracardiac valved conduits placed in the pulmonary circuit. Average age at operation was 7.2 years. Of these, 132 patients had a pulmonary homograft, and 87 had an aortic homograft. Twenty-four patients (11%) died in hospital. Hospital survivors (n = 195) have been followed an average of 29.8 months (SD, +/- 18.4 months). Fourteen patients died during follow-up, almost all related to the complexity of their original cardiac malformation. Thirty-two patients (15%) have required reoperation for conduit-related problems. Actuarial freedom from conduit reoperation is 55 +/- 12% at 5 years. The most common indication for reoperation was calcific stenosis (n = 27). Other indications for reoperation were pseudoaneurysm (n = 2), conduit infection (n = 2), and pulmonary insufficiency (n = 1). Reoperation rate for patients with aortic homografts (16 of 87) compared with that for pulmonary homografts (16 of 132) was not significantly different by the actuarial method. CONCLUSIONS: Long-term function of cryopreserved homograft valved conduits in the pulmonary circulation is disappointing. PMID- 1423993 TI - Surgical connections from ventricle to pulmonary artery. Comparison of four types of valved implants. AB - BACKGROUND: Four types of valved conduits used to correct venous ventricle to pulmonary artery (V-PA) discontinuity were compared. METHODS AND RESULTS: Four hundred fifty-seven patients with congenital heart defects requiring a V-PA connection during the past 25 years were reviewed. Age at implant varied from 1 day to 64 years (mean, 9.1 years). Four types of valved prostheses were used: 1) homograft conduit (HC, n = 178), 2) valved Dacron conduit (VDC, n = 126), 3) polystan conduit (PC, n = 47), and 4) orthotopic pulmonary valve implant (PVI, n = 106). There were 83 early deaths (18.2%) and 34 late deaths (8.5%). Follow-up ranged from 1 month to 22 years (mean, 3.5 years). One hundred eight conduit replacements were performed in 93 patients (21%). The overall patient survival was 73 +/- 2.3%, 67 +/- 3.2%, and 56 +/- 6.8% at 5, 10, and 15 years, respectively. Factors predictive of patient survival were diagnosis (p < 0.001) and valve size (p < 0.001). Age at operation (p < 0.001) and type of valve (p < 0.001) were the only risk factors for valve survival. At 5 years, survival of PVI (89 +/- 5%) and VDC (89 +/- 4%) was significantly better than survival of HC (46 +/- 13%) or PC (57 +/- 9%). CONCLUSIONS: Patients who survived the initial construction of a V-PA conduit had a reasonable long-term survival. A PVI was the most durable prosthesis. A Dacron porcine-valved conduit had significantly better durability than either a cryopreserved homograft or a PC. PMID- 1423994 TI - Partial biventricular repair of pulmonary atresia with intact ventricular septum. Use of an adjustable atrial septal defect. AB - BACKGROUND: Repair of pulmonary atresia with intact ventricular septum (PA-IVS) is one of the more challenging problems in congenital heart surgery. The hypertrophied but hypoplastic right ventricle is suddenly presented with an increased volume load as the right-to-left shunt is abolished by closure of the atrial septal defect (ASD) as part of definitive repair. We have proposed that a restrictive, adjustable ASD that allows a controlled right-to-left shunt may prevent excessive venous hypertension and allow adequate left-sided filling after biventricular repair of PA-IVS. METHODS AND RESULTS: From 1982 through 1991, 39 patients presented for definitive repair of PA-IVS. Nineteen of these patients were thought to be suitable candidates for biventricular repair, and the other 20 underwent a modified Fontan procedure. An adjustable ASD was used in 12 of the 19 patients undergoing biventricular repair. Mean age was 24 months (age range, 5-66 months). Two patients had their ASD snared closed in the operating room after coming off bypass. In the other 10 patients, closure of the ASD could not be tolerated at the time of surgery as evidenced by elevation of right atrial pressures by > 15 mm Hg and decreased blood pressure when closure was attempted. Seven patients had their open ASDs closed by the snare device, and one patient had his ASD narrowed in the early postoperative period. One patient underwent delayed closure 16 months after surgery. There was one hospital death. CONCLUSIONS: The snare-controlled adjustable ASD allows partial biventricular repair of PA-IVS, reducing the risk of low cardiac output and severe venous hypertension in the postoperative period. PMID- 1423995 TI - Left ventricular mechanics and myocyte function after correction of experimental chronic mitral regurgitation by combined mitral valve replacement and preservation of the native mitral valve apparatus. AB - BACKGROUND: Contractile function improves after correction of experimental mitral regurgitation, but ejection performance becomes depressed when mitral valve replacement involves chordal transection. A role for chordal transection in producing the depressed ejection performance was suspected but uncertain. Therefore, in this study, we tested two specific hypotheses: 1) that contractile function would improve and, in conjunction with chordal preservation, would allow for preserved ejection performance and 2) that improved left ventricular contractile function after surgery would be reflected in the function of myocytes isolated from the affected left ventricles. METHODS AND RESULTS: We examined ventricular contractile function and ejection performance and isolated myocyte function after correction of experimental mitral regurgitation (chordal rupture) with mitral valve replacement that involved chordal preservation. After 3 months of chronic mitral regurgitation, the average regurgitant fraction of seven dogs was 0.77 +/- 0.04. End-diastolic volume had increased from 79 +/- 5 to 132 +/- 10 cm3 (p < 0.05). At that time, all indexes of left ventricular contractile function were depressed. Three months after mitral valve replacement with chordal preservation, end-diastolic volume fell to 100 +/- 4 cm3 (p < 0.05). At this time, all indexes of contractile function had returned to normal. End-systolic stress and ejection fraction after mitral valve replacement were similar to their baseline levels. Viscosity-velocity curves (analogous to force-velocity curves) of myocytes isolated from the affected left ventricles were similar to those of myocytes isolated from normal left ventricles. CONCLUSIONS: We conclude that mitral valve replacement with chordal preservation allows ventricular contractile function to return to normal. Normal global ventricular function, in turn, is associated with normal function of the individual myocytes that compose the left ventricular chamber. Further, chordal preservation allowed for loading and ejection performance to return to premorbid levels. PMID- 1423997 TI - Preoperative risk factors that predict hospital length of stay in coronary artery bypass patients > 60 years old. AB - BACKGROUND: The ability to predict prolonged length of stay (LOS) is essential to control escalating hospital costs. Operative mortality is a poor predictor of LOS; morbidity as defined by hospitalization for > 14 days after coronary artery bypass graft surgery (CABG), appears to be responsible for increasing costs. The purpose of this study was to measure preoperative predictive indicators of increased LOS with an eventual plan to offer alternative cost-benefit therapeutic options. METHODS AND RESULTS: Nine hundred twenty-four consecutive patients (age, 60-86 years) undergoing CABG were retrospectively studied by means of the Cox proportional hazards model. Seventeen variables, excluding death, were analyzed and quantified as to importance, and point totals were calculated for each patient. Scores were 12 for congestive heart failure and intra-aortic balloon assist device; 10, creatinine > 2; 6, intra-aortic balloon assist device only; 5, congestive heart failure only; 3, obesity; 6, age > 75 years; 3, age 70-75 years; and 2, 65-69 years. CONCLUSIONS: Increasing index score directly correlated with an exponential increase in LOS. These data substantiate the hypothesis that a mathematical model can predict LOS in CABG patients and may offer rational alternative strategies in delivering cost-effective health care. PMID- 1423996 TI - Aortoventriculoplasty in infants and children. AB - BACKGROUND: When aortic valve replacement is required in infants or small children with complex left ventricular outflow tract obstruction (LVOTO) or aortic incompetence (AI), the diameter of the annulus may limit the size of the prosthesis that can be safely inserted, and aortoventriculoplasty (AVP) may be required. To assess the results of this procedure in the pediatric age group, we reviewed our results in 19 patients who underwent AVP from May 1986 to April 1991. METHODS AND RESULTS: Patient age ranged from 1 day to 18 years (mean, 5.9 years), with six patients < 2 years of age and 13 patients younger than 5 years. Operative indications included complex LVOTO after aortic valvotomy and/or subaortic resection (six), severe AI after valvotomy or aortic valve replacement (four), severe AI with bacterial endocarditis (one), truncus arteriosus with truncal insufficiency (three), failure of an apical-aortic conduit (three), and combined aortic stenosis and mitral stenosis (two). In all patients, valve insertion was performed after patch enlargement of the annulus and septum. Associated procedures included coronary artery reimplantation in five patients and mitral valve replacement in two. Mechanical valve prostheses were used in 15 patients and allografts in four. There were three hospital deaths (16%; 70% confidence limit, 9-26%), two in patients with severe pulmonary vascular disease, and no late deaths. Actuarial survival was 84 +/- 8% at 1 month and beyond (mean follow-up, 2.5 years). Complications have included complete heart block (one), residual ventricular septal defect (one), and early postoperative peripheral embolus (one). No late thromboembolic events have occurred. No patient has clinical or echocardiographic evidence of significant residual LVOTO or AI. CONCLUSIONS: These data indicate that AVP may be performed at low risk and that it is an effective procedure for complex LVOTO or AI in infants and small children. PMID- 1423998 TI - Interaction of age and preoperative risk factors in predicting operative mortality for coronary bypass surgery. AB - BACKGROUND: Models for predicting operative mortality for coronary bypass surgery assume that preoperative risk factors affect mortality to the same extent in all patients groups. METHODS AND RESULTS: To determine whether certain preoperative risk factors disproportionately increase operative mortality in the elderly, 663 consecutive elderly patients (age 75 years or older) and 1,464 younger patients (age 65 or younger) undergoing isolated coronary bypass surgery between 1982 and 1990 were studied. Hospital mortality was significantly greater in the elderly patients than in younger patients (7.5% versus 1.8%; relative risk, 4.5). Univariate analysis identified age, prior coronary artery bypass grafting, congestive heart failure, left main disease, New York Heart Association functional class, hypertension, prior myocardial infarction (MI), and preoperative atrial fibrillation as associated with mortality. Multivariate analysis was then used to construct a model to describe the risk of operative mortality in terms of selected risk factors. However, comparison of observed mortality rates with those predicted by the model revealed problems with the model's goodness of fit. Further testing revealed that young patients without prior MI had a mortality rate lower by an order of magnitude than either younger patients with prior MI or elderly patient groups with and without MI. Two separate models were therefore constructed stratifying by the presence of prior MI. This resulted in a significant improvement in the fit of the models to the observed data. CONCLUSIONS: These results suggest that the impact of risk factors on the elderly may be significantly different from the effect of these risk factors on younger patients. Models for predicting outcome after bypass surgery should be tested for potential interactions between age and risk factors. PMID- 1423999 TI - Survival analysis of octogenarian patients with coronary artery disease managed by elective coronary artery bypass surgery versus conventional medical treatment. AB - BACKGROUND: In view of the increasing age of the U.S. population, the use of coronary artery bypass surgery in the management of the elderly patients with coronary artery disease needs to be better defined. METHODS AND RESULTS: To evaluate the effects of medical and surgical therapy on octogenarian patients with coronary artery disease in our institution, we retrospectively reviewed 177 consecutive octogenarians who underwent cardiac catheterization over a 5-year period. Sixty-five of these patients were found to have significant coronary artery disease without severe valvular disease. Elective coronary artery bypass surgery was performed in 36 patients, whereas 29 patients were continued on maximization of medical therapy and not referred to the surgical service. Left ventricular ejection fractions (LVEF) were similar for the two groups, whereas the surgical patients had slightly higher average number of diseased coronary vessels and slightly higher levels of angina. Univariate survival analysis of 20 variables, including the choice of medical versus surgical treatment and the associated conditions, was performed by Mantel-Cox testing of the paired Kaplan Meier product limit survival curves stratified by the subgroups of each variable. The variables found to be significant were then included in a multivariate survival analysis using the Cox proportional hazards regression model. The treatment choice, LVEF, level of angina, and presence of any aortic and/or mitral valvular disease at the time of cardiac catheterization were found to be independent prognostic indicators of survival in the follow-up period of 26 +/- 16 months. The 3-year probability of survival rates for the surgical patients and medical patients were 77.4% and 55.2%, respectively (p = 0.0294). The New York Heart Association functional class of the surgical group decreased significantly from a mean preoperative level of 3.4 +/- 0.5 to a mean level of 1.2 +/- 0.6 at the follow-up interview (p < 0.01), whereas it did not significantly change for the medical group from a baseline mean level of 2.8 +/- 1.3 to a mean follow-up level of 2.5 +/- 1.0. CONCLUSIONS: We conclude that coronary artery bypass surgery provided improved long-term survival and functional benefit compared with conventional medical treatment in a small group of octogenarian patients in our institution. PMID- 1424000 TI - Observational comparison of event-free survival with medical and surgical therapy in patients with coronary artery disease. 20 years of follow-up. AB - BACKGROUND: The purpose of this study was to describe the long-term event-free survival patterns of patients with significant coronary artery disease treated medically versus patterns of those treated surgically and to evaluate the factors associated with improved event-free survival. METHODS AND RESULTS: We studied the results of 5,824 patients undergoing medical and surgical therapy for ischemic heart disease from 1969 to 1984, with follow-up to 1991. Events considered for this evaluation were nonfatal myocardial infarction or cardiovascular death. The Cox proportional hazards model was used to determine factors differentially affecting surgical event-free survival. The survival benefits previously reported for bypass surgery in this population were largely preserved when event-free survival was examined. The two factors associated with significant event-free survival benefits for surgically treated patients were more severe coronary artery disease and a more recent surgery data. Patients with more severe coronary obstruction had a greater relative improvement with surgery in event-free survival than did patients with less severe anatomic disease. Event-free survival with surgery progressively improved over the period of the study and, by 1984, was significantly better than medical therapy for most patient subgroups. Patients with poor prognosis because of risk factors such as older age, severe angina, or left ventricular dysfunction had a risk reduction with surgery proportional to their overall risk under medical therapy. CONCLUSIONS: Higher risk patients with more severe disease (due to either coronary disease or other risk factors and age) should be considered for coronary revascularization because it is in these patients that coronary artery bypass graft surgery has the greatest impact in reducing future cardiovascular events. PMID- 1424002 TI - Vasomotor response to ergometrine and nitrates of saphenous vein grafts, internal mammary artery grafts, and grafted coronary arteries late after bypass surgery. AB - BACKGROUND: In vitro studies have shown that the vasomotor response of internal mammary artery to vasoactive agents differs from that of saphenous vein. METHODS AND RESULTS: To assess whether the response in vivo to methylergometrine and to nitrates differs in saphenous vein grafts, internal mammary artery grafts, and coronary arteries, 25 patients were studied more than 6 months (range, 6-96 months) after surgery. Angiograms of saphenous vein grafts (n = 11) or mammary artery grafts (n = 14) were obtained in basal conditions, after intravenous infusion of 0.4 mg methylergometrine, and after intragraft infusion of 1 mg isosorbide dinitrate. Computerized quantitative angiography was used to assess the changes in luminal diameter of the bypass graft and of the grafted coronary artery (n = 11). Methylergometrine reduced the diameter of saphenous vein grafts by 6.9 +/- 7.4%, from 3.26 +/- 0.71 to 3.05 +/- 0.76 mm (p < 0.01), and that of grafted coronary arteries by 9.3 +/- 7.2% (NS compared with saphenous vein grafts), from 2.08 +/- 0.49 to 1.89 +/- 0.49 mm (p < 0.005). The diameter of internal mammary artery grafts did not change significantly, from 3.27 +/- 0.42 to 3.25 +/- 0.44 mm (-0.3 +/- 5.1%, p < 0.02 compared with saphenous vein grafts and p < 0.002 compared with coronary arteries). After isosorbide dinitrate, the diameter of both grafted coronary arteries and mammary artery grafts increased significantly (respectively to 2.46 +/- 0.62 mm and 3.44 +/- 0.43 mm), the vasodilatation being greater (p < 0.002) in coronary arteries (+17.8 +/- 9.8% in proportion to basal diameter, p < 0.001) than in mammary grafts (+5.5 +/- 3.3%, p < 0.001). The diameter of saphenous vein grafts returned to control values (3.28 +/- 0.70 mm, NS compared with basal); the changes in luminal diameter after nitrates (+0.7 +/- 3.1%, NS) were significantly smaller than for mammary artery grafts (p < 0.01) and for grafted coronary arteries (p < 0.001). CONCLUSIONS: Unlike internal mammary artery grafts, saphenous vein grafts constrict in response to methylergometrine and do not dilate in response to nitrates. These differences in vasomotor response could reflect heterogeneity in the sensitivity of vascular smooth muscle to these agents or differences in the basal level of vasomotor tone. PMID- 1424001 TI - Differences in vasomotor control between human gastroepiploic and left internal mammary artery. AB - BACKGROUND: Internal mammary artery grafts have a greater long-term patency rate than do saphenous vein grafts. This has in part been attributed to the difference in endothelial function of arterial and venous vessels. The use of the gastroepiploic artery in coronary artery bypass grafting has become popular recently because of its similarity to internal mammary artery. In this study, we compared the endothelial responses of gastroepiploic and left internal mammary arteries to vasoactive substances. METHODS AND RESULTS: Gastroepiploic and left internal mammary arteries were obtained during surgery from patients undergoing elective coronary artery bypass surgery. Vascular rings of both graft types were studied in organ bath experiments. Relaxation responses to metacholine and sodium nitrite were similar in rings of both arteries. In contrast, bradykinin induced potent relaxations in rings of the gastroepiploic artery but not in rings of the left internal mammary artery. Furthermore, there was a inverse correlation of maximal metacholine-induced relaxations with increasing age. CONCLUSIONS: The resemblance of relaxations induced by metacholine and sodium nitrite in both gastroepiploic and left internal mammary arteries suggests a similar activation and behavior of the L-arginine pathway in both arteries. The difference in bradykinin-induced relaxations may reflect a prostaglandin metabolism in the gastroepiploic artery different from that in the left internal mammary artery. Furthermore, maximal metacholine-induced relaxation in rings of the left internal mammary artery shows an age dependency that was not observed in rings of the gastroepiploic artery. PMID- 1424003 TI - Physiological and pharmacological responses of arterial graft flow after coronary artery bypass grafting measured with an implantable ultrasonic Doppler miniprobe. AB - BACKGROUND: The present study was designed to investigate physiological and pharmacological responses of the arterial graft flow measured by the directly implanted ultrasonic pulsed Doppler miniprobe after coronary artery bypass grafting (CABG). METHODS AND RESULTS: Our original 5-MHz, 5-mm-diameter, Doppler mini-flow probe catheter, which has four silicone brims in front to facilitate its fixation onto the graft without direct suture, was attached onto internal thoracic artery (ITA) and gastroepiploic artery (GEA) grafts during CABG in 10 patients. Approximately 2 weeks postoperatively, when the patient's condition was quite stable without medication, changes of flow velocity in those grafts induced by catecholamine, exercise, taking meals, and coronary vasodilating drugs were measured. Dobutamine significantly increased both ITA and GEA graft flow velocity (p < 0.01), whereas dopamine had no distinct positive effect. Upon the patient taking meals, the GEA graft showed an 83% increase of the flow velocity (p < 0.05), whereas the ITA graft showed no significant change. Walking exercise for 6 minutes increased both grafts' flow velocity up to two times that of control values (p < 0.01). Oral intake of coronary vasodilating drugs showed no significant effect. After the investigation was completed, the probe was removed easily at bedside without difficulty. CONCLUSIONS: Using this implantable Doppler miniprobe, postoperative function in the individual coronary bypass graft under various conditions was effectively investigated. PMID- 1424005 TI - Effects of dynamic cardiomyoplasty on regional wall motion, ejection fraction, and geometry of left ventricle. AB - BACKGROUND: Dynamic cardiomyoplasty may provide functional and hemodynamic improvement in patients with heart failure. The purpose of this study was to investigate the effects of cardiomyoplasty on global ejection fraction, regional wall motion, and geometry of the left ventricle. METHODS AND RESULTS: These parameters were determined in 10 patients submitted to cardiomyoplasty for treatment of refractory heart failure by left ventricular (LV) angiography. The studies were performed before and 16.5 +/- 4.8 months after cardiomyoplasty with the myostimulator turned on. They were repeated 24 +/- 1 hours with the myostimulator turned off in eight patients. LV ejection fractions were determined by the area-length method, and the centerline method was used for assessment of regional wall motion. LV geometry was studied by LV major-to-minor axis ratio and sphericity index. A LV ejection fraction improvement from 15 +/- 8% to 30.9 +/- 8.3% (p < 0.01) was demonstrated with the myostimulator turned on after cardiomyoplasty. The values with the myostimulator turned off were 23 +/- 13%, remaining higher than the values observed before surgery (p < 0.05). Regional wall motion analysis showed an improvement in all studied regions. Regarding the LV shape, the left ventricle became markedly more spheric in the diastole. CONCLUSIONS: Dynamic cardiomyoplasty may improve LV function in selected patients. The analysis of LV wall motion corroborated these results, and these changes were associated with modifications in the LV geometry. PMID- 1424004 TI - Modeling distribution of donor hearts to maximize early candidate survival. AB - BACKGROUND: Priority for cardiac transplantation should reflect the relative waiting list mortality and operative mortality of outpatient candidates and critical candidates. METHODS AND RESULTS: To determine how to distribute donor hearts for maximal overall survival, a Markov model of eight states was constructed from current statistics for outpatient sudden death, deterioration to critical status, operative mortality for outpatients, and operative mortality for critical candidates. Because the fraction of hearts offered to critical candidates varied, expected survival at 1 year was calculated. To determine the factors most critical in determining priority policy, current conditions were then varied over a fourfold range. Priority for critical candidates maximized overall candidate survival (with and without transplantation), increasing 1-year survival to 78% compared with 66% if hearts were offered only to outpatients. The benefit of giving priority to critical patients persisted when current group mortality rates were individually halved or doubled because these rates were still small compared with the 100% expected mortality of critical patients without transplantation. If the outpatient sudden death rate and the operative mortality for critical patients were doubled simultaneously, however, there was a slight negative impact on survival if critical candidates received priority. Regardless of changes in subgroup outcomes, the distribution of donor hearts had a relatively modest impact on survival because of the large excess of candidates. CONCLUSIONS: Critical candidates for transplantation should continue to receive priority even if their operative mortality increases above current levels. However, postoperative outcomes must be assessed in relation to changing pretransplantation risks. Distribution of donor hearts will be most beneficial when it is possible to identify the waiting patients at greatest risk for sudden death and deterioration without transplantation. PMID- 1424006 TI - Rejection after cardiac transplantation. A time-related risk factor analysis. AB - BACKGROUND: The determinants of early and repeated episodes of acute rejection after cardiac transplantation remain elusive. METHODS AND RESULTS: To gain insight into this phenomenon, a multivariate analysis for repeated events was applied to 229 patients receiving 249 transplanted hearts between 1981 and July 1, 1991 (595 rejection episodes). The mean frequency of rejection per patient after initial cardiac transplantation was 1.2 at 3 months, 1.8 at 1 year, and 2.8 at 5 years. The pattern of rejection was characterized by an early period of higher risk (greatest during the first month) followed by a low constant risk that continued throughout the period of follow-up (maximum, 9.5 years). By multivariate analysis, risk factors were identified for the likelihood of subsequent rejection after a previous rejection episode (or time of transplantation). Triple-drug immunosuppression plus induction therapy yielded a higher risk of early subsequent rejection compared with other baseline immunotherapy protocols, but it also provided the greatest freedom (95%) from rejection-related death during the first year. Risk factors in the constant phase of hazard included younger age at transplant, female donor and/or recipient, longer donor ischemic time, greater HLA donor-recipient mismatch, and an increased number of previous rejection episodes. CONCLUSIONS: Immunologic and other patient-specific characteristics as well as rejection history predict the likelihood of future rejection events. The value of any antirejection protocol must be evaluated both in terms of rejection episodes and rejection-related deaths. Future analyses may identify specific high- and low-risk patient subsets for rejection, which may provide a more rational basis for altering the amount of chronic immunosuppressive therapy. PMID- 1424008 TI - Imaging of pulmonary artery and vein anastomoses by transesophageal echocardiography after lung transplantation. AB - BACKGROUND: In patients after isolated lung transplantation, the postoperative course may be complicated by dysfunction of the pulmonary artery and vein anastomoses. METHODS AND RESULTS: Pulmonary artery and vein anastomoses in 11 transplanted lungs (four left, four right, and three bilateral lungs) in 10 patients were studied 1 day to 11 months after operation by transesophageal echocardiography (TEE). All 14 pulmonary vein anastomoses, all seven right (100%) and five of seven (71%) left pulmonary artery anastomoses could be visualized by TEE. Thrombosis of a left pulmonary vein anastomosis could be identified by TEE and successfully treated by thrombolysis. TEE detected a significant stenosis in one right and one left pulmonary artery anastomosis; anastomoses dysfunction were confirmed by cardiac catheterization and pulmonary angiography and successfully treated by surgical correction in both cases. CONCLUSIONS: Function and morphology of pulmonary artery and vein anastomoses in patients after isolated lung transplantation can reliably be assessed by TEE. In patients with suspected dysfunction of an anastomosis, TEE may be considered the diagnostic technique of choice. PMID- 1424007 TI - Photopheresis versus corticosteroids in the therapy of heart transplant rejection. Preliminary clinical report. AB - BACKGROUND: Photopheresis is a technique in which reinfusion of mononuclear cells exposed to UV-A light ex vivo after in vivo treatment with 8-methoxypsoralen initiates host-immunosuppressive responses. METHODS AND RESULTS: To determine if photopheresis safely reverses International Society for Heart and Lung Transplantation (ISHLT) rejection grades 2, 3A, and 3B without hemodynamic compromise, 16 heart transplant patients with ISHLT rejection grades 2, 3A, and 3B were randomized to photopheresis or corticosteroid therapy. The average number of mononuclear cells treated with each photopheresis procedure was 9.8 +/- 9.1 x 10(9) (mean +/- SD). Photopheresis and corticosteroids reversed eight of nine and seven of seven episodes of rejection, respectively. The median time from initiation of treatment to rejection reversal was 25 days (range, 6-67 days) in the photopheresis group and 17 days (range, 8-33 days) in the corticosteroid group. Hemodynamics were normal before either treatment and did not change after reversal of rejection. No adverse reactions occurred with photopheresis, and all patients in either treatment group are alive. CONCLUSIONS: These preliminary, short-term results in prospectively randomized patients indicate that photopheresis may be as effective as corticosteroids for treating ISHLT rejection grades 2, 3A, and 3B. The apparently low toxicity and potential efficacy of photopheresis warrant further analysis of its role in the prevention and treatment of heart transplant rejection. PMID- 1424009 TI - Doppler examination of superior vena caval flow for the detection of acute cardiac rejection. AB - BACKGROUND: Doppler echocardiographic studies have previously documented abnormalities of mitral flow during acute rejection similar to those seen in patients with "restrictive" physiology. As central venous flow is known to be abnormal in such patients, it was proposed that examination of superior vena caval flow with Doppler echocardiography might be useful for the detection of acute cardiac rejection. METHODS AND RESULTS: Thirty orthotopic cardiac transplant patients, 15 of whom had acute cardiac rejection diagnosed by endomyocardial biopsy, were studied within 36 hours of biopsy. Superior vena caval Doppler flow velocities as well as mitral and tricuspid flow velocities were recorded using a Hewlett-Packard Sonos 500/1000 echocardiograph system. Examinations were performed blinded to the biopsy result. Mitral and tricuspid peak early flow velocities in the nonrejector group were similar to those seen in normal subjects (mitral, 70 +/- 5 cm/sec; tricuspid midexpiratory apnea, 50 +/- 11 cm/sec). Superior vena caval flow was abnormal with 13 of 15 patients demonstrating a biphasic pattern of forward flow with dominant diastolic flow. In the 15 patients with acute cardiac rejection, both mitral and tricuspid flow velocities developed a "restrictive"-type pattern with increased peak early flow velocities (mitral, 89 +/- 24 cm/sec; tricuspid midexpiratory apnea, 63 +/- 19 cm/sec; p < or = 0.05 versus nonrejectors) and decreased mitral early flow velocity deceleration times (rejectors, 97 +/- 26 msec; nonrejectors, 144 +/- 41 msec; p < or = 0.05). The pattern of superior vena caval flow became markedly abnormal with a virtually complete loss of forward systolic flow (rejectors, 4.4 +/- 6.6 cm/sec; nonrejectors, 26.1 +/- 8.8 cm/sec at midexpiratory apnea; p < or = 0.0001). In 10 of 15 patients, systolic forward flow was absent. If acute rejection was defined as forward systolic flow < or = 17 cm/sec, then sensitivity was 100%, specificity was 80%, and predictive accuracy was 90%. CONCLUSIONS: During acute cardiac rejection, forward systolic superior vena caval flow is markedly diminished compared with nonrejectors. This is accompanied by other Doppler echocardiographic features consistent with the development of "restrictive" physiology. It is postulated that the loss of forward systolic flow in the superior vena cava is due to diminished long-axis shortening of the right ventricle associated with acute cardiac rejection. PMID- 1424010 TI - Rigid ring fixation of the mitral annulus does not impair left ventricular systolic function in the normal canine heart. AB - BACKGROUND: Previous studies suggest that rigid fixation of the mitral annulus with an annuloplasty ring may impair left ventricular (LV) systolic performance. We used load-insensitive indexes of global and regional LV contractile mechanics to test the hypothesis that rigid fixation of the mitral annulus alters LV systolic function. METHODS AND RESULTS: Global and regional LV systolic mechanics were compared in 10 dogs during two mitral annular conditions: rigidly fixed and freely mobile. Carpentier-Edwards annuloplasty rings (20-24 mm) were inserted using a special buttressing suture technique that permitted alternate cinching of the ring down onto the annulus and subsequent removal away from the annulus. Aortic flow was measured with an electromagnetic flow probe, LV pressure by a micromanometer, and LV wall thickness and three near-orthogonal LV endocardial chamber dimensions using piezoelectric crystals during four sequential ring conditions: 1) down, 2) away, 3) down, and 4) away. The following parameters were analyzed during each ring condition to assess global LV systolic function: end systolic chamber elastance (end-systolic pressure-volume relation), fiber elastance (end-systolic stress-volume relation), preload recruitable stroke work, and myocardial stress-strain relation. Additionally, regional LV systolic performance was assessed using the end-systolic pressure-diameter relation and a regional analog of preload recruitable stroke work. No significant differences in any of these measurements of LV systolic mechanics were observed between the two mitral annular conditions. CONCLUSIONS: Rigid fixation of the mitral annulus alters neither global nor regional LV systolic function in anesthetized, open chest dogs with normal ventricles. PMID- 1424011 TI - Clinical significance of mild rejection of the cardiac allograft. AB - BACKGROUND: The clinical status of heart transplant patients during mild rejection (lymphocytic infiltrate without myocyte necrosis) has not been previously reported. This study examined the frequency and outcome of mild rejection associated with allograft dysfunction sufficient in magnitude to be evident on clinical exam (two or more abnormal findings) and/or two-dimensional echocardiography. METHODS AND RESULTS: The study population consisted of 59 patients, 50 men and nine women 14-61 years old (mean, 1.7 +/- 0.8 years) with a mean follow-up of 1.7 +/- 0.8 years after transplant. All were receiving cyclosporine, azathioprine, and prednisone. A total of 108 episodes of mild rejection were detected (frequency, 1.8 episodes per patient). Detailed records of clinical findings were available for 94 episodes. Thirty-five (37%) of these 94 mild rejections were associated with allograft dysfunction: hypotension, n = 4; elevated jugular venous pressure, n = 14; S3, n = 13; rales, n = 10; sinus rate > or = 110 beats per minute, n = 25; atrial fibrillation, n = 5; bradycardia < 60, n = 1; and systolic dysfunction on echo, n = 14. Treatment with high-dose steroids was clinically indicated in eight mild rejection episodes (9%) with allograft dysfunction. Of the remaining 86 untreated episodes, eight (30%) of 27 with allograft dysfunction versus six (10%) of 53 without allograft dysfunction progressed to moderate rejection on subsequent biopsy (chi 2 = 5.15, p = 0.02). Episodes with allograft dysfunction occurred earlier than those without dysfunction (15.4 +/- 2.8 weeks versus 34.4 +/- 5.5 weeks, p = 0.01) when baseline immunosuppression was higher. CONCLUSIONS: Our findings indicate that 1) mild rejection is frequently associated with cardiac allograft dysfunction; 2) nine percent of mild rejection episodes may be accompanied by severe allograft dysfunction or arrhythmias, requiring aggressive treatment; 3) mild rejection associated with allograft dysfunction occurs earlier than that without allograft rejection; 4) untreated, mild rejection episodes with allograft dysfunction progress to moderate rejection more frequently than those without allograft dysfunction. These episodes require increased surveillance for progression. PMID- 1424012 TI - Ventricular volume growth after cardiac transplantation in infants and children. AB - BACKGROUND: Intermediate-term survival after pediatric cardiac transplantation continues to improve. However, little is known about cardiac function and especially ventricular growth in young patients after cardiac transplantation. The purpose of this study was to evaluate serially the hemodynamics, left ventricular (LV) volume, and ventricular function after cardiac transplantation in infants and children. METHODS AND RESULTS: Indications for cardiac transplantation were dilated cardiomyopathy (eight patients), hypoplastic left heart syndrome (six patients), and postoperative structural congenital heart disease (three patients). The age at time of transplant ranged from 7 days to 15 years (median, 3.5 years). The mean follow-up was 30.3 months (range, 13-46 months). Serial annual cardiac catheterizations were performed 1 year (17), 2 years (15), and 3 years (seven) after transplant. Measurements included right and left heart pressures, cardiac index, and LV volume and ejection fraction (Lange). Cumulative results (expressed as mean +/- SD) were pulmonary artery pressure, 14.9 +/- 3.2 mm Hg; LV end-diastolic pressure, 7.7 +/- 2.6 mm Hg; cardiac index, 3.5 +/- 0.52 l/min.m-2; and pulmonary vascular resistance, 2.02 +/- 0.76 units/m2. LV end-diastolic volume increased as patients grew, so that left ventricular end-diastolic volume remained 90 +/- 14% of that predicted for body surface area. The ejection fraction was 99 +/- 6% of that predicted. There was no evidence of chronic rejection by endomyocardial biopsy. No accelerated coronary artery atherosclerosis was identified. CONCLUSIONS: Serial studies in these young patients demonstrate normal hemodynamics and LV function after cardiac transplantation. Cardiac transplantation is associated with normal LV volume growth despite immunosuppression and denervation. PMID- 1424013 TI - The implantable defibrillator: an electronic bridge to cardiac transplantation. AB - BACKGROUND: Sudden cardiac death (SCD) is common among patients awaiting heart transplantation. Medical management of SCD may fail due to lack of efficacy or adverse side effects. The implantable cardioverter-defibrillator (ICD) may extend patient survival until a donor heart is available. METHODS AND RESULTS: We reviewed 16 patients listed for transplantation between November 1988 and October 1991 who underwent ICD implantation for ventricular arrhythmias refractory to medical management. Mean age was 51.4 +/- 11.4 years (range, 19-66 years), mean ejection fraction was 15.4 +/- 3.0% (range, 10-21%), and underlying cardiomyopathy was ischemic (12 patients), valvular (one patient), or dilated (three patients). There was no mortality from ICD insertion. Fourteen patients were discharged before transplantation, and two patients remained in the hospital until transplantation. Twelve patients underwent transplantation after a mean of 155.7 +/- 113.7 days (range, 3-319) on the transplant list. The ICD delivered shocks for tachyarrhythmia associated with near syncope in 15 of 16 patients. ICD shocks numbered > 10 in five patients, 5-9 in three patients, and 1-4 in seven patients. There was no morbidity or mortality attributed to patch electrode removal. CONCLUSIONS: We conclude that the ICD can be implanted with minimal morbidity in transplant candidates, allowing the patients to be ambulatory and to leave the hospital while awaiting heart transplantation. In patients at risk of SCD, the ICD is an effective electronic bridge to transplantation. PMID- 1424014 TI - Detrimental effects of temperature on the efficacy of the University of Wisconsin solution when used for cardioplegia at moderate hypothermia. Comparison with the St. Thomas Hospital solution at 4 degrees C and 20 degrees C. AB - BACKGROUND: We have previously reported the superior protective properties of the University of Wisconsin (UW) solution compared with the St. Thomas solution (ST) in the rat heart subjected to the deep hypothermia (4 degrees C), thus demonstrating its possible use in cardiac transplantation. We thought it was important to evaluate the potential of the UW solution as a cardioplegic solution under the moderately hypothermic (20 degrees C) conditions of routine intraoperative myocardial protection. METHODS AND RESULTS: Isolated rat hearts were subjected to 60 minutes of ischemia at 4 degrees C or 30 (or 60) minutes of ischemia at 20 degrees C with UW, ST, and ST plus 100 mM K (ST + 100) solutions. Coronary flow, mechanical function, endothelial function, and ultrastructure were observed. Mean time (seconds) to infuse 10 ml of cardioplegic solution under constant pressure, a measure of coronary vascular resistance at 4 degrees C and 20 degrees C, respectively, for each solution were ST, 69.2 +/- 6.9 and 64.7 +/- 3.8; UW, 142.2 +/- 8.8 and 187.2 +/- 10.0 (p < 0.01); and ST + 100, 78.2 +/- 8.0 and 176 +/- 8.1 (p < 0.001). Mean recovery values of cardiac output (expressed as percentage of its preischemic value) after 60 minutes of ischemia at 4 degrees C were ST, 95.5 +/- 2.1%; UW, 93.0 +/- 2.4%; and ST + 100, 96.5 +/- 1.5%. After 30 minutes of ischemia at 20 degrees C, values were ST, 88.0 +/- 1.3%; UW, 72.2 +/- 3.6% (p < 0.005 versus ST); and ST + 100, 53.3 +/- 1.8% (p < 0.001 versus ST). CONCLUSIONS: The efficacies of UW and severely hyperkalemic cardioplegic solutions are affected by the degree of hypothermia under which they are used. Under moderate hypothermia (20 degrees C), severe hyperkalemia induces a marked increase in coronary vascular resistance that is associated with impaired myocardial protection. These studies discourage the use of UW for routine intraoperative cardioplegic arrest where the degree of hypothermia cannot be readily controlled. The ST solution does not share this constraint. PMID- 1424015 TI - In vitro assessment of the effects of glucose added to the University of Wisconsin solution on myocyte preservation. AB - BACKGROUND: University of Wisconsin solution (UWS) has been successfully used for liver transplantation and may be beneficial for hypothermic cardiac storage. The addition of glucose may enhance myocardial preservation. METHODS AND RESULTS: Cultured human ventricular myocytes (eight dishes per group) were stored at 0 degree C for 12 hours in either unmodified UWS or UWS with glucose (1, 3, 10, 30, or 100 mmol/l). Cells were assayed for protein by spectrofluorometry and adenine nucleotides by high performance liquid chromatography after storage. Protein recovery, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and total adenine nucleotides (ATP+ADP+AMP) were all depleted after storage (p < 0.0001 by ANOVA). Protein recovery (p < 0.005), ATP (p < 0.05), and ADP (p < 0.05) were increased with glucose administration compared with unmodified UWS. Improvement was maximal using 30 mmol/l (protein, 0 mmol/l = 0.48 +/- 0.14 and 30 mmol/l = 0.65 +/- 0.11 mg per dish; ATP, 0 mmol/l = 3.08 +/- 0.63 and 30 mmol/l = 4.32 +/- 0.90 nmol/mg protein; ADP, 0 mmol/l = 3.76 +/- 0.80 and 30 mmol/l = 4.63 +/- 0.38 nmol/mg protein, mean +/- SD). Total adenine nucleotides tended to increase at any glucose concentration (p = 0.07 by ANOVA) and were significantly better with 30 mmol/l glucose (0 mmol/l = 7.61 +/- 1.58 and 30 mmol/l = 9.62 +/- 1.08 nmol/mg protein). CONCLUSIONS: Increasing the glucose concentration from 0 to 30 mmol/l improved adenine nucleotide and cellular protein preservation in this in vitro assessment. PMID- 1424016 TI - Effects of in vivo cyclosporine administration on endothelium-dependent responses in isolated vascular rings. AB - BACKGROUND: Although in vitro studies suggest that cyclosporine (CSA) reduces endothelium-dependent relaxation (EDR), controversy still remains regarding the effects of in vivo CSA treatment. The lack of correlation between CSA dosages and therapeutic efficacy has led to an increased emphasis on the monitoring of CSA blood levels in clinical immunosuppression. We therefore studied the effects of in vivo administration to rats of a therapeutic level of CSA on endothelium dependent vascular reactivity using isolated vascular rings obtained from these animals. METHODS AND RESULTS: Thoracic aorta vascular rings from adult Sprague Dawley rats treated with subcutaneous injections of CSA (5 mg/kg/day) for 7 and 21 days were suspended in Krebs buffer containing indomethacin and tested for EDR to methacholine (1 x 10(-7) to 5 x 10(-5) M) and for endothelium-independent relaxation (EIR) to nitroprusside (5 x 10(-6) M). Mean whole blood CSA trough levels were 978 +/- 287 and 2,865 +/- 379 ng/ml for the 7- and 21-day groups, respectively. No differences were noted in both EDR and EIR between untreated control rats and the treated groups. Maximal EDR (mean +/- SEM) was 83 +/- 3%, 79 +/- 2%, and 81 +/- 3% for control rats and 7- and 21-day treatment groups, respectively. Relative developed tension (grams) to 5 x 10(-6) M phenylephrine was significantly (p < 0.05) increased in the CSA-treated groups (1.03 +/- 0.01 and 1.08 +/- 0.01 g at 7 and 21 days, respectively, versus 0.73 +/- 0.01 g (p = NS) for untreated controls). Minimal endothelial disruption was evident on scanning electron microscopy in the CSA-treated animals. CONCLUSIONS: We conclude that CSA-induced vascular dysfunction may be in part a result of an increased sensitivity to direct vasoconstriction rather than of an attenuation of endothelium-dependent relaxation. PMID- 1424017 TI - Extracorporeal membrane oxygenator rescue in children during cardiac arrest after cardiac surgery. AB - BACKGROUND: Conventional cardiopulmonary resuscitation (CPR) for cardiac arrest after open-heart surgery in children is often unsuccessful despite the ability to perform open-chest massage. The purpose of this study was to review our results with mechanical support as rescue therapy in children with sudden circulatory arrest after cardiac surgery. METHODS AND RESULTS: From 1981 through 1991, we have used mechanical support with an extracorporeal membrane oxygenator (ECMO) circuit for cardiac support in 33 children. Eleven of the 33 patients (age, 15 +/ 7 months) suffered cardiac arrest intractable to conventional open-chest massage 39 +/- 15 hours after an open-heart procedure. The mean duration of CPR was 65 +/ 9 minutes until ECMO flow was started. ECMO support was continued for 112 +/- 8 hours. One patient had ECMO discontinued due to bleeding (survived); three were discontinued from ECMO and died from neurological complications; and one died of cardiac dysfunction. Sepsis on ECMO was seen in one patient (survived). Overall early survival was seven of 11 (64%) with one patient requiring heart transplantation due to irreversible cardiac dysfunction. One child died late (1 month) after ECMO support. There were no long-term sequelae in the survivors. CONCLUSIONS: We conclude that ECMO rescue in children with postcardiotomy cardiac arrest is a feasible option in selected patients even after prolonged CPR (as long as 60 minutes). PMID- 1424018 TI - Extracorporeal membrane oxygenation in children after cardiac surgery. AB - BACKGROUND: From August 1982 to May 1991, 65 children (32 boys), 1 day to 14 years old, received extracorporeal membrane oxygenation (ECMO) 0-50 hours after cardiac surgery. Forty-four (67.7%) were weaned, with 23 (35.4%) survivors. METHODS AND RESULTS: Analysis of 29 pre-ECMO factors including diagnosis, age, sex, blood gas data, systemic pressures, atrial pressures, ventricular function, and renal function was performed. Preoperative systemic ventricular shortening fraction was statistically less in survivors. The need for dialysis and length of support were predictors of survival once ECMO was initiated. There were five late deaths 6 days to 5 years after discharge; none were related to ECMO. The remaining 18 patients have been followed for a mean of 37.5 months (range, 1-85 months). Seventeen are New York Heart Association functional class I, with one patient still hospitalized. CONCLUSIONS: ECMO allows for myocardial recovery in the majority of patients with refractory postcardiotomy failure and permits some patients to survive who would not have otherwise. PMID- 1424019 TI - Survival prediction in staged heart transplantation using Jarvik-7 artificial heart. AB - BACKGROUND: Because mechanical circulatory assist as a bridge to heart transplantation places a further strain on current donor shortage as well as on medical cost containment, safe and effective use of the device is essential. METHODS AND RESULTS: To predict survival before undertaking staged heart transplantation with the Jarvik-7 artificial heart, our 58 attempts were reviewed retrospectively. Scores of 1-4 were given for six preoperative factors based on results obtained by univariate and multivariate analyses between survivors and nonsurvivors of staged heart transplantation: transplant rejection (scored 4: S4) or postoperative heart failure (S3) as the indication, recipient height < 175 cm (S3), body surface area < 1.8 m2 (S3), hyperbilirubinemia > 24 microM/l (S2), weight < 60 kg (S2), and age > 40 years (S1). Of 14 survivors, 13 had a total score < 4 (sensitivity, 93%), with an average score of 1.6 in contrast to 5.5 for 44 nonsurvivors (p < 0.001). Among 26 patients scored < 4, 21 had heart transplantation, of whom 13 left the hospital. Of 32 patients scored > or = 4, only four could be discharged after transplantation (specificity, 70%). CONCLUSIONS: Multiple preoperative factors successfully predicted transplantability and survival in staged heart transplantation. The results underscore the importance of preoperative condition and patient selection to achieve successful and effective use of Jarvik-7 as a bridge to heart transplantation. PMID- 1424020 TI - Right ventricular/arterial coupling in the patient with left ventricular assistance. AB - BACKGROUND: Improvements are known to occur in right ventricular (RV) ejection fraction after the use of a left ventricular assist device (LVAD); less is known, however, about the mechanism of this improvement. The concept of ventricular/arterial coupling was applied to investigate whether systolic pump function or afterload reduction was the major contributing factor leading to the improvement in RV ejection fraction. METHODS AND RESULTS: Eight consecutive patients who underwent Novacor LVAD implantation as a bridge to transplantation were studied intraoperatively with transesophageal echocardiogram and a catheter tip manometer to examine the RV end-systolic pressure-area relation (ESPAR) before and after LVAD implantation. Fractional area change (FAC) obtained by echocardiogram was used as an approximation of ejection fraction. End-systolic elastance (Ees), area axis intercept of ESPAR (A0), maximal area (Amax), and pulmonary effective arterial elastance (Ea) were obtained. RV FAC improved from 0.20 +/- 0.09 to 0.29 +/- 0.13 (p < 0.05). There was a decrease in Ea from 12.06 +/- 5.79 to 4.92 +/- 2.51 mm Hg/cm2 (p < 0.01), which indicated a reduction in RV afterload. A0 increased from -0.14 +/- 7.81 to 6.83 +/- 9.42 cm2 (p < 0.05), which implied impaired systolic pump function. There was no difference in Ees and Amax. CONCLUSIONS: The concept of ventricular/arterial coupling predicts that an increase of A0 (reduced RV systolic mechanics) decreases FAC, whereas a reduction in Ea improves FAC. The improvement in RV FAC (improved RV pump performance) may result from the effect of reduced Ea (afterload reduction) overwhelming the effect of increased A0. Afterload reduction is the most likely mechanism by which RV ejection fraction improves after LVAD implantation. PMID- 1424021 TI - Compositional analysis of a modified University of Wisconsin solution for extended myocardial preservation. A study of the left ventricular pressure-volume relation. AB - BACKGROUND: The University of Wisconsin solution (UW) has been shown to be superior to the use of traditional types of simple crystalloids in extended heart preservation. This study was designed to determine the necessity of four potentially redundant components in UW. MATERIALS AND METHODS: Forty canine hearts (n = 8 in each group) were preserved for 6 hours under hypothermic (1-2 degrees C), nonperfused conditions in unmodified UW, UW with an extracellular or reversed composition of sodium and potassium (UW-E), UW with chloride instead of lactobionate (UW-L), UW without raffinose (UW-R), and UW without hydroxyethyl starch (UW-HS). The left ventricular functions were assessed in an isolated heart preparation equipped with a computerized servo-volume pump to measure the pressure-volume relation. The systolic function was expressed in elastance derived from the end-systolic pressure-volume relation, and total ventricular performance was expressed in preload recruitable stroke work area derived from the stroke work-end-diastolic volume relation. Diastolic compliance was derived from the end-diastolic pressure-volume pressure relation. The results were compared with a control group with no ischemia. There was no significant deterioration in left ventricular systolic contractile functions as demonstrated by the analysis of elastance and the preload recruitable stroke work area in any of the modifications of UW. However, significant deterioration in the diastolic compliance occurred in the UW-E and UW-HS groups. A similar trend was found in the UW-L group, although it was not statistically significant, whereas the diastolic compliance was preserved in the UW-R group. CONCLUSIONS: The intracellular electrolyte composition and the hydroxyethyl starch are important in the preservation of left ventricular diastolic function, whereas the omission of raffinose was inconsequential. The replacement of lactobionate by chloride had less untoward functional effects compared with studies of other solid organ preservation. PMID- 1424022 TI - Assessment of function, perfusion, metabolism, and histology in hearts preserved with University of Wisconsin solution. AB - BACKGROUND: University of Wisconsin solution has shown promise for prolonged cardiac preservation. This study compared the effects of 24-hour cold storage and perfusion preservation techniques by assessment of function, perfusion, metabolism, and histological changes. METHODS AND RESULTS: Three groups of rabbit hearts (n = 6 each) were evaluated: 1) control with immediate reperfusion, 2) continuous perfusion preservation, and 3) cold storage. Hearts were reperfused for 30 minutes, and left ventricular systolic pressure (LVSP) was measured by isovolumetric balloon (LVEDP, 20 mm Hg). We used 201Tl to assess perfusion and 14C-acetate to assess metabolism by macroautoradiography. LVSP was similar for controls and hearts preserved with continuous perfusion (134.8 +/- 2.1 versus 112.2 +/- 6.0 mm Hg, respectively). Hearts preserved with cold storage techniques were significantly worse (36.7 +/- 6.0 versus 134.4 +/- 8.2 mm Hg, p < 0.001). Controls showed homogeneous perfusion and metabolism, whereas hearts in the continuous perfusion group showed mild hypoperfusion and histological damage (26.4 +/- 2.7% of left ventricular cross section). Hearts in the cold storage group had 51.7 +/- 1.2% of the left ventricle hypoperfused and damaged. Histology in the control group was normal; in the perfused group, there were only mild changes; and in the cold storage group, there were extensive derangements of cellular architecture. CONCLUSIONS: Continuous perfusion of the heart with 4 degrees C modified University of Wisconsin solution provided function comparable to that of control. Conversely, cold storage showed extremely poor return of function. Autoradiography confirmed mild perfusion and metabolism abnormalities in control and continuous perfusion hearts, whereas there was marked derangement of cellular architecture, perfusion, and metabolism in the cold storage hearts. PMID- 1424023 TI - Oxyhemoglobin dissociation during hypothermic blood cardioplegia arrest. AB - BACKGROUND: Coronary sinus effluent contains desaturated blood during the first few seconds of hypothermic cardioplegia infusion in humans. This occurs despite the high affinity of hemoglobin for oxygen at a low temperature and alkaline pH. The present study quantitates oxyhemoglobin dissociation during hypothermic cardioplegic arrest. METHODS AND RESULTS: Three infusions of a 4 degrees C alkalotic blood cardioplegia solution were given into the cross-clamped aortic root during 1 hour of cardioplegic arrest. Paired aortic root and coronary sinus blood samples were obtained before and shortly after initiating cardiopulmonary bypass and at t = 5 seconds and 30 seconds during each cardioplegia infusion. Throughout the study, the hemoglobin saturation in the aortic root samples was 100%. The mean coronary sinus hemoglobin saturation at t = 5 seconds during hypothermic cardioplegia infusion ranged from 63.0% to 66.5% (p < 0.05 coronary sinus compared with aortic root samples). The coronary sinus hemoglobin saturation approximated the aortic root hemoglobin saturation at t = 30 seconds during hypothermic cardioplegia infusion. The mean PO2 of the aortic root samples ranged from 214 to 307 mm Hg during hypothermic cardioplegia infusion. The mean PO2 of the t = 5 seconds coronary sinus samples ranged from 31 to 39 mm Hg, whereas the mean PO2 of the t = 30 seconds coronary sinus samples ranged from 85 to 119 mm Hg during cardioplegia infusion (p < 0.05 coronary sinus compared with aortic root samples). CONCLUSIONS: Oxygen dissociates from hemoglobin contained in a hypothermic, alkalotic blood cardioplegia solution during the nonperfused phase of cardioplegic arrest. However, the only oxygen delivered to the myocardium during the infusion of a hypothermic alkalotic blood cardioplegia solution is oxygen physically dissolved in the solution. PMID- 1424024 TI - Coronary endothelial injury by cold crystalloid cardioplegic solution in neonatal lambs. AB - BACKGROUND: Hypothermic cardioplegia generally improves the recovery of the mechanical function of the heart after ischemia, but some components of cold cardioplegia may produce endothelial injury that can offset the protective effects of cardioplegia. This study was undertaken to evaluate the effect of extremely hypothermic cardioplegia on the recovery of coronary endothelial and cardiac mechanical function after ischemia in the immature heart. METHODS AND RESULTS: Three groups of eight isolated, blood-perfused, neonatal lamb hearts each had myocardial temperature maintained at 10 degrees C during 2 hours of global ischemia but received hourly doses of crystalloid cardioplegic solution at temperatures of 10 degrees C (group A), 4 degrees C (group B), and 2 degrees C (group C). The percent recovery of isovolumic left ventricular maximum developed pressure in groups A (86.6 +/- 7.7) and B (90.5 +/- 7.5) was higher than in group C (78.6 +/- 6.3), and maximum dP/dt in groups A (89.6 +/- 8.6) and B (89.5 +/- 5.7) was higher than in group C (79.4 +/- 9.0) at 30 minutes of reperfusion (p < 0.05). Groups A (136.8 +/- 20.9) and B (142.8 +/- 27.7) achieved higher recovery of coronary blood flow (as percentage of baseline) at 15-minute reperfusion than group C (108.5 +/- 26.2), and myocardial oxygen consumption was higher in groups A (68.3 +/- 14.6, 92.1 +/- 21.1) and B (68.8 +/- 19.9, 85.3 +/- 25.5) than in group C (46.3 +/- 14.7, 57.2 +/- 14.2) at 15 and 30 minutes of reperfusion, respectively (p < 0.05). Percent recovery of the coronary vascular resistance responses to 10(-7) M concentration of an endothelium-dependent vasodilator (acetylcholine) in groups A (71.9 +/- 9.0) and B (66.2 +/- 23.1) was higher than in group C (24.2 +/- 14.3) (p < 0.05), whereas responses to 3 x 10(-5) M concentration of endothelium-independent vasodilator (nitroglycerin) were the same. CONCLUSIONS: Excessively cold cardioplegic solution may cause endothelial dysfunction (reduced acetylcholine response) and reduced recovery of mechanical function in the neonatal heart. PMID- 1424025 TI - Heat shock. A new approach for myocardial preservation in cardiac surgery. AB - BACKGROUND: Recent studies have indicated that heat shock (HS) induces protective genes and HS protein (HSP) expression, which enhances cellular tolerance to ischemic injury. The present study sought to determine if 42 degrees C blood cardioplegia could be used to induce HSP expression and improved myocardial salvage after 2 hours of cardioplegic arrest. METHODS AND RESULTS: To study this, pig hearts (n = 6) on cardiopulmonary bypass were subjected to HS by continuous infusion to the globally arrested heart of warm blood cardioplegia (K+ = 30 meq/l) at 42 degrees C for 15 minutes followed by 2 hours of intermittent hypothermic (4-6 degrees C) hyperkalemic (30 meq/l) crystalloid cardioplegic arrest and 1 hour of reperfusion (heat shock group). The control group (n = 6) was subjected to only 2 hours of hypothermic crystalloid cardioplegic arrest followed by 1 hour of reperfusion without HS. Left ventricular performance, coronary blood flow, and creatine kinase release were determined before arrest and during reperfusion. Prearrest control biopsies were taken in a separate group of pigs (n = 6) for both HSP and superoxide dismutase activity. Additional biopsies were taken for the same measurements in both control and HS groups at the completion of reperfusion. In a single additional pig in both the control and HS groups, biopsies were taken during the study to estimate changes in HSP expression. The cytosolic protein of ventricular tissue was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the HSP70 family protein was examined by Western blot analysis using monoclonal antibodies. HSP was found to be increasingly expressed from control levels after 15 minutes of HS pretreatment, increasing progressively to a level significantly above the non-HS group. Associated with this increased expression of HSP was a significant increase in superoxide dismutase activity in the HS animals and significant improvement in both global and regional functions and reduced creatine kinase release. CONCLUSIONS: The results show that preconditioning the heart with HS improves postischemic ventricular performance and attenuates cellular injury. HS induces a change in cellular metabolism, prompting the expression of HSP and improving antioxidant activity, leading to improved function and reduced tissue injury during ischemia and reperfusion. PMID- 1424026 TI - Effect of aging on intracellular Ca2+, pHi, and contractility during ischemia and reperfusion. AB - BACKGROUND: To investigate the effect of aging on myocardial ischemic and reperfusion injury, cytosolic calcium (Ca2+), intracellular pH (pHi), and mechanical performance were measured in isolated perfused rabbit hearts. METHODS AND RESULTS: Hearts of mature (4-5-month-old) and aged (28-38-month-old) rabbits were loaded with 10 microM of fura-2 or 2',7'-bis(2-carboxyethyl)-5(6) carboxyfluorescein (BCECF) and subjected to 30 minutes of normothermic ischemia and reperfusion. Cytosolic Ca2+ levels ([Ca2+]) during the nonbeating ischemic period and end-diastolic Ca2+ levels ([EDCa2+]) during reperfusion were determined from the fura-2 fluorescence ratio of emission at 510 nm during excitation at 340 and 380 nm. pHi was obtained from the ratio of emission at 530 nm during excitation at 450 and 490 nm. [Ca2+] of the mature group (n = 8) increased from 188 +/- 19 nM (mean +/- SEM) to 373 +/- 32 nM during ischemia, and that of the aged group (n = 7) increased from 242 +/- 17 to 465 +/- 20 nM. The rise of [Ca2+] of the aged group was significantly greater (p < 0.05) than that of the mature group. Immediately after reperfusion, [EDCa2+] in both groups returned to the preischemic level. pHi decreased to the same extent (from 7.2 to 6.7) during ischemia and returned to preischemic values during reperfusion. The mature group recovered 84 +/- 3% of left ventricular peak pressure after ischemia, whereas the aged group recovered only 55 +/- 3% (p < 0.005). Functional recovery was inversely correlated to the increase of [Ca2+] during ischemia (r = 0.66). CONCLUSIONS: Aged hearts exhibit greater accumulation of [Ca2+] during ischemia and less functional recovery after ischemia than mature hearts. The greater rise of [Ca2+] in aged hearts is not a result of the difference of buffering capacity for ischemia-induced acidosis. PMID- 1424027 TI - Alternative techniques of cardioplegia. AB - BACKGROUND: Although normothermic cardioplegia has been used with acceptable clinical results, no studies have previously been performed to determine the metabolic consequences of these various techniques of myocardial protection. Therefore, we have performed a randomized clinical trial to assess the effects of three cardioplegic techniques on myocardial metabolic recovery. METHODS AND RESULTS: Seventy-four patients undergoing coronary artery bypass graft surgery were randomized to receive normothermic antegrade blood cardioplegia (n = 25), normothermic retrograde blood cardioplegia (n = 23), or intermittent cold antegrade blood cardioplegia (n = 26). Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and cardiac creatine kinase isoenzyme (CK-MB) release was assessed after surgery. Warm antegrade cardioplegia maximized myocardial oxygen consumption during cardioplegic delivery. Postoperative CK-MB release was less after warm antegrade cardioplegia, but the difference was not statistically significant. Warm retrograde cardioplegia resulted in the greatest degree of anaerobic lactate production but did not increase morbidity and mortality. Perioperative myocardial infarctions and postoperative low-output syndrome were most common after cold cardioplegia, but this trend was not statistically significant. During warm antegrade cardioplegia, adenosine triphosphate (ATP) was metabolized to diffusible precursors, which were washed out during cardioplegic infusion. Warm retrograde cardioplegia produced a breakdown of ATP to inosine and hypoxanthine, small molecules that accumulated during the cross-clamp period and were not washed out, perhaps because of inadequate perfusion with retrograde delivery. During cold cardioplegia, ATP was dephosphorylated, and adenosine diphosphate, adenosine monophosphate, and adenosine accumulated. These compounds were not regenerated to ATP but were not washed out of myocytes because they are large anionic molecules. CONCLUSIONS: Intermittent cold cardioplegia inhibited mitochondrial function but prevented the degradation of adenine nucleotides. Warm antegrade cardioplegia had the greatest myocardial oxygen consumption, and warm retrograde cardioplegia had the greatest anaerobic lactate production. There were no differences in clinical outcomes between cardioplegic groups. PMID- 1424028 TI - Effect of normothermic blood cardioplegia on postoperative conduction abnormalities and supraventricular arrhythmias. AB - BACKGROUND: Conduction defects and supraventricular tachycardia (SVT) are common after myocardial revascularization using current methods of cold hyperkalemic blood or crystalloid cardioplegia. The current retrospective study was undertaken to assess the influence of normothermic blood cardioplegia on conduction defects and SVT. METHODS AND RESULTS: The initial 92 patients underwent cardiopulmonary bypass (CPB) at 28 degrees C and blood cardioplegia at 6-8 degrees C. The subsequent 120 patients underwent CPB and blood cardioplegia at 37 degrees C. In all patients, cardioplegia was initially given by a combined antegrade/retrograde technique. The incidence of new postoperative conduction disturbances was significantly less in the normothermic group (p < 0.001): 27.5% versus 57.6% immediately after surgery; 9.2% versus 41.3% 1 day after surgery; 4.2% versus 32.6% 2 days after surgery; 1.7% versus 19.6% on hospital discharge; and 1.7% versus 17.4% on late follow-up. The incidence of supraventricular arrhythmias was not statistically different: 40.0% warm versus 42.4% cold. The groups were identical except that mean cross-clamp times were significantly longer (73.8 versus 60.1 minutes), mean number of grafts were significantly higher (3.7 versus 3.4), and mean cardioplegia volume was significantly greater (5,627 versus 3,710 ml) in the warm group (p < 0.05). In addition, the warm group had a higher incidence of prior transmural anterior myocardial infarctions (35% versus 9.8%, p < 0.001) and emergency operation (16.7% versus 6.5%, p < 0.05). Creatine kinase (CK) MB release was significantly less in the warm group immediately after operation (24.9 versus 60.9 units/l) and on POD1 (19.2 versus 46.5 units/l) (p < 0.001). CONCLUSIONS: Normothermic cardioplegia is associated with a marked decrease in new and permanent conduction disturbances and postoperative CK-MB release. This suggests that a significant factor in the pathogenesis of conduction blocks is cold-related injury. Supraventricular arrhythmias were not affected by the type of cardioplegia given. PMID- 1424029 TI - Global left ventricular performance and regional systolic function after suture annuloplasty for chronic mitral regurgitation. AB - BACKGROUND: In surgery for chronic mitral regurgitation, the mitral subvalvular apparatus, including annulus, may play an important role in preserving left ventricular (LV) performance. The suture annuloplasty for mitral regurgitation allows annular contraction of the mitral valve. The potential effects of suture annuloplasty on the postoperative LV performance have not been fully defined. METHODS AND RESULTS: Global and regional LV function in 12 patients with suture annuloplasty were compared with 12 patients with conventional mitral valve replacement (MVR). Cineangiography and echocardiography were obtained before and 10.8 months after surgery. End-diastolic volume index and end-systolic volume index decreased significantly in both groups after surgery (p < 0.01). Ejection fraction remained unchanged in the suture annuloplasty group, whereas it decreased significantly in the MVR group after surgery (p < 0.01). There was a significant inverse relation between ejection fraction and end-systolic wall stress in the two groups after surgery (suture annuloplasty group, r = -0.69, p = 0.01; MVR group, r = -0.60, p = 0.04). The intercept on the y axis was significantly (p < 0.005) higher in the suture annuloplasty group than in the MVR group. In the suture annuloplasty group, cross-sectional area ejection fraction at the mitral valve level and at the papillary muscle level by LV two-dimensional echocardiography remained unchanged after surgery. In the MVR group, they decreased significantly after surgery (p < 0.01). There was a significant correlation between the cross-sectional area ejection fraction and the global ejection fraction at both levels after surgery. Therefore, the improvement of the regional wall motion can be attributed to the improvement of the global LV performance after suture annuloplasty. CONCLUSIONS: These data suggest that suture annuloplasty can provide more desirable postoperative LV systolic performance than conventional MVR by preserving both the contraction of the mitral annulus and the mitral valvular-ventricular interaction. PMID- 1424030 TI - Retrograde is superior to antegrade continuous warm blood cardioplegia for acute cardiac ischemia. AB - BACKGROUND: Theoretically, the efficacy of continuous warm blood cardioplegia may be improved when administered retrogradely (RCWBC) rather than antegradely (ACWBC) in the setting of acute regional ischemia because of enhanced oxygen and substrate delivery to myocardial tissue distal to an acute coronary artery occlusion. METHODS AND RESULTS: Eighteen Yorkshire swine were instrumented for quantification of global left ventricular systolic, diastolic, and regional left anterior descending coronary artery (LAD) zone mechanics before and after 10 minutes of mid-LAD occlusion, followed by 60 minutes of cardiac arrest using continuous warm blood cardioplegia. Initially, 20 ml/kg of 37 degrees C oxygenated blood cardioplegia (hematocrit, 22 +/- 0.6%) was infused antegradely, followed by maintenance of 75 ml/min ACWBC (n = 9) or 60-100 ml/min of RCWBC (n = 9). LAD occlusion was released 20 minutes after cardiac arrest (30 minutes total LAD ischemia), simulating surgical revascularization. Postischemic recovery of global preload recruitable stroke work was nearly complete with RCWBC but significantly depressed with ACWBC (84.9 +/- 9.5% versus 52.4 +/- 5.1%, respectively; p < 0.01). LAD regional stroke work was also well preserved postischemically with RCWBC but showed no functional recovery and systolic bulging after ACWBC (87.4 +/- 13.7% versus -11.36 +/- 7.46% of control values; p < 0.01). Global diastolic stiffness calculated using the beta-coefficient of an exponential end-diastolic pressure-versus-volume relation was unchanged with ACWBC but increased significantly after RCWBC (from 0.027 +/- 0.002 to 0.028 +/- 0.003 mm Hg/ml and from 0.028 +/- 0.003 to 0.036 +/- 0.004 mm Hg/ml, respectively). CONCLUSIONS: These data suggest that with acute regional ischemia, both global and ischemic zone regional systolic function are depressed by ACWBC, whereas RCWBC affords adequate protection of contractile performance. However, a loss of diastolic compliance may result as a consequence of warm retrograde delivery. PMID- 1424031 TI - Protection of platelets during long-term extracorporeal membrane oxygenation in sheep with a single dose of a disintegrin. AB - BACKGROUND: Both short- and long-term extracorporeal membrane oxygenation (ECMO) causes platelet loss and dysfunction. Bitistatin is a reversible inhibitor of the platelet glycoprotein IIb/IIIa receptor. This study tests the hypothesis that inhibition of platelets by bitistatin during initial contact with the perfusion circuit preserves platelet number and function during long-term ECMO in sheep. METHODS AND RESULTS: Bitistatin, purified from crude snake venom, was tested for its effect on platelet count, responsiveness to ADP, release of platelet factor 4, and prevention of surface-adsorbed glycoprotein IIIa in vitro and during 24 hours of ECMO in nine splenectomized sheep. During simulated extracorporeal circulation, 0.5-1.0 microgram/ml bitistatin significantly prevented platelet adhesion, attenuated release of sheep platelet factor 4, and preserved platelet responsiveness to ADP. During ECMO at 1.8 l/min for 24 hours, a single dose of bitistatin (200 micrograms/kg) (n = 4) produced higher platelet counts (p = 0.0002) and suppressed release of platelet factor 4 (p = 0.035) for 16 hours compared with five control animals. This dose of bitistatin caused an immediate inhibition of platelet aggregation; however, between 4 and 24 hours of perfusion, platelets of bitistatin-treated animals were more responsive to ADP (p < 0.0001) compared with platelets in control animals. The amount of glycoprotein IIIa antigen extracted by Triton X-100 from the perfusion circuits was reduced in bitistatin-treated sheep. CONCLUSIONS: A single dose of bitistatin given before blood contact with the ECMO circuit briefly inhibits platelet adhesion and aggregation but thereafter preserves platelet numbers and function and suppresses alpha-granule release for 12-16 hours of ECMO. PMID- 1424032 TI - Effect of human recombinant erythropoietin on reduction of homologous blood transfusion in open-heart surgery. A Japanese Multicenter study. AB - BACKGROUND: Recombinant human erythropoietin (EPOCH) has been shown to increase erythropoiesis; therefore, EPOCH has been used in conjunction with autologous blood predonation (ABP) before surgery. However, the administration methods of EPOCH to obtain an adequate volume of ABP before open-heart surgery have not been determined. METHODS AND RESULTS: The effects of EPOCH on harvesting ABP and decreasing homologous blood transfusion (HBT) in open-heart surgery were examined prospectively in 205 patients treated in a 29-institute multicenter study. Single dose of 3,000, 6,000, or 9,000 IU of EPOCH were administered for 2 weeks (two or three times per week) without ABP (group 1, n = 69) or for 3 weeks (two or three times per week) with ABP (group 2, n = 97) and compared with control subjects (n = 39). Preoperative blood hemoglobin increase (delta Hb[g/dl]) was < 1.0 g/dl in group 1. When EPOCH was given three times a week, the delta Hb in each subgroup of group 2 was 0.6 +/- 1.1 (control), 2.1 +/- 1.3 (3,000 IU), 2.4 +/- 1.4 (6,000 IU), and 2.8 +/- 1.5 (9,000 IU), which was significantly higher than the control (p < 0.05) and was dose dependent. The HBT rates in patients with a moderate perioperative blood loss of between 15 and 50 ml/kg were 75.0% (control), 35.7% (3,000 IU), 52.9% (6,000 IU), and 66.7% (9,000 IU) in group 1, and respective volumes in group 2 were 40.0% (control), 20.0% (3,000 IU), 26.9% (6,000 IU), and 12.5% (9,000 IU). The overall HBT rate of EPOCH-treated patients with a moderate blood loss was 50% (20 of 40) in group 1 and 21% (13 of 62) in group 2. The HBT rate was significantly reduced by combination of preoperative EPOCH treatment (three times per week) and ABP (p < 0.0001). CONCLUSIONS: Dose-dependent increase of blood hemoglobin level was observed by EPOCH treatment with ABP; combination of EPOCH treatment and ABP can reduce HBT during open-heart surgery. PMID- 1424033 TI - Comparative efficacy of ring and suture annuloplasty for ischemic mitral regurgitation. AB - BACKGROUND: Patients with ischemic mitral regurgitation (MR) represent a therapeutic challenge, and results after combined valve replacement and revascularization have been poor. Valve repair is a promising approach, but the optimal method of repair is not known. METHODS AND RESULTS: In 60 patients with coronary artery disease and 3+ or 4+ MR, we used intraoperative Doppler echocardiography to study the efficacy of Carpentier-Edwards ring (n = 27) and commissural suture (n = 33) annuloplasty. Patients with ruptured papillary muscles, torn chordae, and ballooning or scalloping of the leaflets were excluded. Ring and suture groups were similar in preoperative ejection fraction (35 +/- 14% and 34 +/- 17%), MR grade (3.5 +/- 0.5 and 3.4 +/- 0.6), and acuity of MR (41% and 33% acute) (p = NS). Postoperatively, the ring group achieved a lower residual MR grade than the suture group (0.5 +/- 0.5 versus 1.5 +/- 1.1; p < 0.001), and the mitral annular diameter was reduced to a greater extent in the ring group (by 1.5 +/- 0.5 cm versus 0.5 +/- 0.4 cm; p < 0.001). Success (> or = 2 grade MR reduction) was more frequent in the ring than in the suture group (96% versus 67%, p < 0.01). One-year survival was similar (74 +/- 9% ring, 71 +/- 8% suture). Follow-up Doppler studies showed a higher mean gradient (4.0 +/- 1.2 mm Hg) and smaller valve area (2.1 +/- 0.5 cm2) in the ring group, but the postoperative New York Heart Association class was similar in both groups (83% versus 74% class I-II). CONCLUSIONS: Ring annuloplasty provides a more effective reduction of ischemic MR and a higher success rate than the suture technique. This may be related to uniform rather than localized shortening of the annulus and a greater reduction in annulus diameter. PMID- 1424034 TI - Mitral valve repair using Carpentier techniques in patients more than 70 years old. Early and late results. AB - BACKGROUND: Mitral valve incompetence in elderly patients raises the problem of whether to replace or to repair the mitral valve. The purpose of this study is to review our experience with mitral valve repair in patients > 70 years old. METHODS AND RESULTS: Between 1986 and 1991, 79 consecutive patients > 70 years old underwent mitral valve repair by Carpentier techniques. The most frequent cause was degenerative valve disease (65 of 79). Preoperative echocardiography showed that 6% of the patients had type I, 88% type II, and 5% type III mitral valve dysfunction. Anatomic lesions encountered at surgery confirmed the preoperative echocardiographic findings, with 88% of the patients with a leaflet prolapse either of the posterior leaflet (56%) or of both the anterior and posterior leaflets (32%). Multiple surgical procedures were required in each patient. Posterior leaflet resection was the most common technique used (76%). Prosthetic ring annuloplasty was used in 96% of patients. Associated procedures were performed in 21.5% of cases. Three patients died, for an operative mortality of 3.8%. One patient (1.3%) required reoperation for residual mitral insufficiency. Nonfatal complications related to the patients' preoperative condition were noted in more than half of the patients. Echocardiography obtained before discharge revealed absent or minimal mitral insufficiency in 91% of patients and mild mitral insufficiency (2+/4+) in 9%. Follow-up was available for 74 of 76 patients (97.3%) and ranged from 3 months to 6 years (mean, 22 months). Two patients (2.6%) were lost to follow-up. Sixty patients (89%) were in New York Heart Association functional class I or II. Seven patients died and one required reoperation. Actuarial analysis of the results showed overall survival at 5 years 81 +/- 11%; freedom from thromboembolism, hemorrhage, and reoperation 97 +/- 5%, 97 +/- 5%, and 98 +/- 4%, respectively. Color-coded echo Doppler studies obtained in 67 patients at the time of follow-up showed absent or minimal MI (91%) (n = 61), and mild MI in 9% (n = 6). CONCLUSIONS: These data suggest that mitral valve repair using Carpentier techniques should now be considered as the procedure of choice in patients of any age referred for mitral insufficiency. PMID- 1424035 TI - Initial results of combined anterior mitral leaflet plication and ventricular septal myotomy-myectomy for relief of left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy. AB - BACKGROUND: Several operations (most commonly ventricular septal myotomy-myectomy and also mitral valve replacement) have been performed to relieve symptoms and obstruction to left ventricular outflow in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: In an effort to establish an alternative to mitral valve replacement, combined septal myotomy-myectomy and suture plication of the anterior mitral valve leaflet was performed in a subgroup of 36 severely symptomatic patients with obstructive HCM. These patients were selected primarily because the mitral leaflets were judged morphologically at the time of operation to be of sufficient size relative to that of the outflow tract to represent a risk for residual systolic septal contact and outflow obstruction. The effects of operation were assessed in 34 patients; of the 33 with preoperative symptoms, 28 (85%) reported substantial functional improvement after surgery over an average follow-up of 2.2 years. Of 29 patients with complete hemodynamic data, basal outflow gradient was obliterated or reduced substantially by surgery (to < or = 35 mm Hg) in 26 patients (90%) and for the group from 81 +/ 42 to 16 +/- 24 mm Hg (p < 0.001); provocable gradient with isoproterenol infusion also decreased considerably (from 109 +/- 50 to 47 +/- 25 mm Hg; p < 0.001). Echocardiographic studies showed that plication limited the systolic anterior motion of anterior mitral leaflet. There was no hemodynamic evidence of mitral stenosis, and in only one patient did mitral regurgitation increase after surgery. CONCLUSIONS: Mitral valve plication combined with myotomy-myectomy in obstructive HCM 1) can be performed safely and does not adversely alter mitral valve function, 2) relieves symptoms and outflow obstruction under basal and provocable conditions, and 3) may represent an alternative to mitral valve replacement in selected patients with elongated and enlarged mitral leaflets. PMID- 1424036 TI - Acute bacterial endocarditis. Optimizing surgical results. AB - BACKGROUND: Acute bacterial endocarditis continues to be a condition with high morbidity. Although the majority of patients are treated by high-dose antibiotics, a high-risk patient group requires surgical intervention, which is the subject of this article. METHODS AND RESULTS: From 1972 to 1991, 3,820 patients underwent heart valve replacement at the Brigham and Women's Hospital, Boston. Of this group, 158 patients underwent surgery for acute bacterial endocarditis: 109 had native valve endocarditis (NVE), and 49 had prosthetic valve endocarditis (PVE). There were 108 men and 50 women with a mean age of 49 years (range, 16-79 years); 64% were New York Heart Association functional class IV before surgery, and 12% of the group had a history of intravenous drug abuse. In both NVE and PVE groups, Streptococcus was the predominant infecting agent. Uncontrolled sepsis, progressive congestive failure, peripheral emboli, and echocardiographically demonstrated vegetations were the most common indications for surgery. Eighty-five percent of patients had a single-valve procedure, 15% had a multivalve procedure, and 34 patients had other associated major cardiac procedures. The operative mortality was 6% in NVE and 22% in PVE. Long-term survival at 10 years was 66% for NVE and 29% for PVE. Freedom from recurrent endocarditis at 10 years was 85% for NVE and 82% for PVE. The main factors associated with decreased survival overall were PVE and nonstreptococcal infection. CONCLUSIONS: The morbidity and mortality after surgical treatment of acute endocarditis depend on the site, the severity, and the subject infected. Early aggressive surgical intervention is indicated to optimize surgical results, especially in patients with nonstreptococcal infection or PVE. PMID- 1424037 TI - Spontaneous host endothelial growth on bioprostheses. Influence of fixation. AB - BACKGROUND: Neither homografts nor bioprostheses have previously been seen to acquire a host endothelium. We previously reported a direct relation between aldehyde tanning and bioprosthesis calcification and the absence of calcification in the absence of aldehyde. METHODS AND RESULTS: Bovine pericardium was 1) treated with 0.625% glutaraldehyde and stored in 4% formaldehyde, 2) treated with 99.5% glycerol, and 3) treated with 99.5% glycerol and stored in formaldehyde (0.25-4%). The treated pericardium was used to construct stentless mitral valve prostheses (of a single pattern) that were implanted in weanling sheep. After the animals were killed, a strip of anterior cusp from annulus to papillary muscle was processed and examined by scanning electron microscopy for the presence of host endothelial growth. Avoidance of aldehyde allowed host endothelial growth in all cases (six of six), and pure aldehyde treatment inhibited growth in five of six animals. Exposure to aldehyde after glycerol treatment interfered with endothelialization significantly; after longer periods of implantation, however, endothelial growth occurred almost invariably in this group (12 of 13 implanted longer than 200 days). For this group, there was a statistically significant difference for duration of implantation between the valves that grew endothelium and those that did not (218.4 +/- 61.9 versus 128.5 +/- 65.4 days). CONCLUSIONS: Aldehyde treatment inhibits endothelial growth. With glycerol treatment, growth is uniformly present. Limited exposure to aldehydes after glycerol treatment inhibits endothelial growth, but this effect was ameliorated by prolonged implantation. The possibility of host endothelium-covered, noncalcifying bioprostheses is now real. PMID- 1424038 TI - Mechanical cardiac valve thrombosis. Is fibrinolysis justified? AB - BACKGROUND: Thrombosis is a serious complication of heart valve replacement, and management is often difficult. In recent years, thrombolytic therapy has been used as the primary technique by some investigators. METHODS AND RESULTS: Sixty four consecutive patients presenting with 75 instances of prosthetic heart valve thrombosis (41 mitral, 33 aortic, one tricuspid) were treated with fibrinolytic agents. Obstructed prosthetic valves comprised 39 tilting disc and 36 bileaflet valves. The time interval between valve replacement and obstruction ranged from 15 days to 192 months (mean, 38 months). Fibrinolytic agents used were streptokinase (42 patients), urokinase (27 patients), or recombinant tissue-type plasminogen activator (six patients). Immediate results of fibrinolytic treatment were 1) full success after one or several consecutive fibrinolytic regimens in 55 cases (73%), 2) incomplete improvement in two cases, and 3) failure in 18 cases, leading to an emergency surgery in nine cases. Nine patients died (four strokes, four cardiac arrests, one hemorrhage). Only one severe hemorrhagic complication was observed, but 11 cases of embolism occurred during fibrinolytic treatment (14.6%) (four major cerebral embolisms with death). The immediate efficacy was better for thrombosed aortic prosthesis than with the mitral prosthesis (85% versus 63%). CONCLUSIONS: Fibrinolytic treatment appears to be an attractive nonsurgical alternative for prosthetic heart valve thrombosis, but because of the risk of cerebral embolism, its use should be reserved for tricuspid valve thrombosis or critically ill patients with mitral or aortic valve thrombosis. The use of a fibrinolytic agent in cases of small, nonobstructive paravalvular thrombosis demonstrated with transesophageal echocardiography needs further studies. PMID- 1424039 TI - From Glenn to Fontan. A continuing evolution. AB - BACKGROUND: Aristotle's and Galen's erroneous understanding of the circulation eventually was rectified, mostly by Colombo and Harvey, who in the 16th and 17th centuries, respectively, provided the foundation to our present knowledge of the pulmonary and systemic circulation. The "indispensability" of the right ventricle was not questioned until the 20th century. Rodbard, in 1948, for the first time successfully bypassed the canine right ventricle by anastomosing the right atrial appendage to the proximally ligated main pulmonary artery. This important experiment triggered a number of other studies that eventually led to the clinical introduction of the Glenn operation in 1959 and the Fontan operation in 1968. METHODS AND RESULTS: Clinical experience with modifications of the original Fontan operation at The Children's Hospital in Boston included 1) direct atrial to-pulmonary artery connection (without valves), 2) cavocaval baffle-to-pulmonary artery connection, 3) bidirectional cavopulmonary artery anastomosis, and 4) fenestrated Fontan approach. The original surgical mortality of 20% has been reduced in 1990-1991 to 4%, including patients with complex pathology other than tricuspid atresia. The incidence of prolonged pleural effusions has also decreased from an earlier 40% to < 5% after bidirectional cavopulmonary artery anastomosis and to 11% after the fenestrated Fontan operation. CONCLUSIONS: Much progress has been made since Dr. Glenn's and Dr. Fontan's epic contributions. Ideally, a more appropriate selection of patients and some of the modifications of the original Fontan operation will have a more favorable impact on early and long-term results. PMID- 1424040 TI - Fenestrated Fontan with delayed catheter closure. Effects of volume loading and baffle fenestration on cardiac index and oxygen delivery. AB - BACKGROUND. The fenestrated Fontan operation has been applied to high-risk patients with univentricular hearts, resulting in improved survival. The purpose of this study was to determine the hemodynamic factors responsible for these improved results. METHODS AND RESULTS. We performed the fenestrated Fontan operation in 17 high-risk patients with univentricular hearts (median age, 3 years; age range, 1.2-25 years). High-risk characteristics were depressed ventricular function and/or hypertrophy (n = 12), atrioventricular valve insufficiency (n = 5), pulmonary artery distortion (n = 6), elevated pulmonary vascular resistance (> 2 units/m2) (n = 4), previously failed Fontan operation (n = 2), or associated Wolff-Parkinson-White syndrome (n = 1). Intraoperative hemodynamic measurements (n = 8) included cardiac index (by aortic flow probe), peripheral arterial O2 saturations, and left and right atrial pressures during inflow occlusion, followed by volume loading with open versus closed fenestration. Mean baffle fenestration was 3.5 mm (range, 2.7-5.0 mm). Multiple regression analysis (cardiac index versus atrial pressure) revealed cardiac index was greater with open than with closed fenestration (p < 0.001) during volume loading. Oxygen delivery (cardiac index multiplied by oxygen content) was also greater with open than with closed fenestration (p < 0.001). Survival was 100% with a mean follow-up of 10.4 months; pleural drainage was high in two patients. Subsequent transcatheter fenestration closure resulted in increased O2 saturation (87 +/- 1% to 96 +/- 0.3%, p < 0.05). CONCLUSIONS. The fenestrated Fontan operation improves survival in high-risk patients by increasing cardiac index and maintaining oxygen delivery, despite mild arterial O2 desaturation. Subsequent transcatheter fenestration closure can be performed after hemodynamic assessment. PMID- 1424041 TI - Abolishment of chronic volume overload. Implications for diastolic function of the systemic ventricle immediately after Fontan repair. AB - BACKGROUND: In patients with a univentricular heart, the chronic ventricular volume overload is acutely abolished by the creation of a Fontan circuit. This results in an immediate reduction of the ventricular cavity size but also in an inappropriate degree of ventricular wall thickness, at least in the early postoperative period. The implications for the diastolic properties of the ventricle are poorly understood. METHODS AND RESULTS: A chronic volume overload through a modified Blalock-Taussig shunt was created in 10 mongrel dogs. Six weeks later, the shunt was occluded percutaneously with a detachable balloon. The left ventricular end-diastolic dimension and posterior wall thickness were measured with transcutaneous echocardiography. Digitized high-fidelity pressure tracings were used to determine the time constant of isovolumic pressure decay, tau. The isovolumic relaxation time (A2-MVO) and time to minimal left ventricular pressure (A2-LVPmin) were recorded. All variables were followed up to 1 month after occlusion of the shunt. One hour after occlusion, there was an incomplete return to baseline values of the echocardiographic left ventricular dimension (+12 +/- 8% of baseline value, p < 0.01). Despite a 31 +/- 14% (p < 0.001) increase of the posterior wall thickness after removal of the volume overload, tau or ventricular relaxation showed no change from control values. In contrast, the early filling wave was blunted, suggesting diminished ventricular suction. A2 MVO (p < 0.01) and A2-LVPmin (p < 0.05) lengthened well above baseline values for up to 1 week after occlusion of the shunt. Over the following month, the volume induced hypertrophy regressed, and indexes of early ventricular filling resumed control values. CONCLUSIONS: We conclude that early after removal of a chronic volume overload, the resultant increase of wall thickness is not associated with impaired relaxation but that viscosity and inertia caused by the increased mass to-volume ratio will impair early ventricular filling. PMID- 1424042 TI - Clinical-pathological correlations of coronary disease progression and regression. AB - The initiation of atherosclerosis may result from blood flow oscillatory shear stress in certain vascular sites (bending points, bifurcations, etc.) producing chronic minimal injury resulting in functional alteration of the arterial endothelium type I injury; experimentally, this is potentiated by atherogenic risk factors such as hypercholesterolemia, hypertension, immunocomplexes, viral infections, and tobacco smoke. Such minimal injury leads to accumulation of lipid and monocytes (macrophages), and subsequently, toxic products released by the macrophages produce damage of the intimal surface with denuding endothelium type II injury or damage, which attracts platelets; all of these cells release growth factors, prompting migration and proliferation of smooth muscle cells and producing a "fibro-intimal lesion" or the outside of the capsule of a predominant "lipid lesion." The lipid lesions surrounded by a thin capsule tend to be small and rupture easily, causing type III injury or damage; that is, they are soft and weak, contain large numbers of macrophages, which may release collagenase and elastase to form abscesses, and by their location, are under the effect of flow shear forces. After plaque disruption there is thrombus formation; when thrombi are small, they can become organized and contribute to the growth of the atherosclerotic plaque; when thrombi are large and occlusive, they lead to the acute coronary syndromes. New data suggest that, at the time of plaque disruption, certain "thrombogenic" risk factors modulate the degree of thrombogenicity and, thereby, the growth of the plaque versus the various acute coronary syndromes. Aside from the need for better understanding of the basic biology of atherogenesis, emphasis on identifying and modifying the primary atherogenic and thrombogenic risk factors should continue for primary prevention. Also, new approaches should focus on the identification, stabilization, and regression of the small "lipid plaques" prone to rupture (these are not necessarily angiographically apparent), as well as on the use of better and safer antithrombotic agents for prevention of progression. PMID- 1424044 TI - Interventions that beneficially influence the evolution of coronary atherosclerosis. The case for calcium channel blockers. AB - Calcium channel blockers have been shown to retard the development of atherosclerosis in rabbits fed cholesterol-rich diets. The mechanism accounting for this effect is controversial but may be by stimulation of cholesteryl ester hydrolase activity in smooth muscle cells, by amelioration of hypercholesterolemia-induced endothelial dysfunction, or by inhibition of smooth muscle cell proliferation and migration. The effect of calcium channel blockers on the evolution of coronary atherosclerosis in humans has been assessed in two clinical trials. In the Montreal Heart Institute trial, nicardipine did not influence the overall rate of progression and regression; however, nicardipine treated patients experienced significantly less progression of minimal lesions, defined as stenoses of < or = 20% severity. In the International Nifedipine Trial on Antiatherosclerotic Therapy, nifedipine had no effect on overall progression and regression but reduced the rate of appearance of new coronary lesions. These studies constitute a potentially important new approach to the management of coronary atherosclerosis. PMID- 1424043 TI - Antithrombotic therapy and progression of coronary artery disease. Antiplatelet versus antithrombins. AB - Coronary artery disease develops and progresses over decades with lipid incorporation and coalescence into the arterial wall, leading to recurrent plaque disruption, thrombosis, and organization into fibromuscular lesions. The role of thrombin in arterial thrombosis is documented by observations that specific thrombin inhibition can completely prevent intraluminal mural thrombus in vivo, even though other factors that activate platelets are not inhibited. Platelet rich thrombi associated with deep injury have a high thrombin content and require blood levels of specific thrombin inhibition with hirudin that are eight to 10 times those required to prevent thrombi associated with lesser injury or stasis. Total prevention of mural thrombus in deeply injured arteries is impossible with aspirin or conventional antithrombotic therapy, which can reduce occlusive thrombus. Thus, conventional antithrombotic therapies can reduce clinical events but are not effective in reducing progression of coronary artery disease. Whether newer antithrombins that can totally prevent mural thrombus after deep injury can be developed and administered orally and chronically without high risk of bleeding and will be able to reduce progression of coronary artery disease is unknown. Lesion growth, vascular injury, acute coronary syndromes, and principles of thrombus formation on ruptured plaque are discussed elsewhere in this issue. This article extends these findings and discusses the prevention and treatment of mural thrombosis, the pivotal role of thrombin in arterial thrombosis, and antithrombotic therapy for the prevention and the progression of coronary artery disease. PMID- 1424045 TI - Atherosclerosis. Potential targets for stabilization and regression. AB - Reviewed are various aspects of atherosclerotic plaque stabilization and regression in humans and experimental animals. Plaque regression is a function of the dynamic balance among initiation, progression, stabilization, and removal of plaque constituents. Pseudoregression, the result of the triad thrombolysis, age- or lesion-dependent arterial dilatation, and relaxation of vasospasm, may readily give rise to angiographic misinterpretation. Although lowering of plasma cholesterol and low density lipoprotein-cholesterol has demonstrated significant clinical benefits in a number of clinical trials, the magnitude of angiographic regressive changes is relatively small despite aggressive lipid-lowering regimens. The emerging need for alternative or complementary therapeutic interventions has been emphasized. In particular, they should be targeted to pivotal cellular or molecular mechanisms in initiation, progression, or stabilization. Potentially important therapeutic targets include the use of antioxidants or free radical scavengers such as Probucol or its analogues, butylated hydroxytoluene, tocopherols, and possibly the tocotrienols. Other therapeutic targets include intimal monocyte-macrophage recruitment, macrophage cholesterol acyltransferase inhibition, stimulation of the high density lipoprotein-mediated reverse cholesterol transport system, smooth muscle cell migration to and proliferation in the arterial intima, and intimal connective tissue synthesis. Whether the isoprenylated proteins associated with the cholesterol biosynthetic pathway will give rise to compounds regulating smooth muscle cell growth has yet to be determined. Because of the importance of thrombosis in the pathogenesis and progression of lesions, the need to develop interventional strategies targeted at endothelial cell thromboresistance and thromboregulation must assume a high priority in future research and development. Other areas of therapeutic promise include the calcium channel blockers and angiotensin converting enzyme inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424046 TI - Intact and altered endothelium in regulation of vasomotion. AB - The endothelium possesses the ability to modulate vascular tone by the release of vasodilator and vasoconstrictor substances, among them endothelium-derived relaxing factor (EDRF) and endothelin. Abnormalities in EDRF generation were demonstrated in various cardiovascular pathophysiological states, specifically atherosclerotic vascular disease, congestive heart failure, and essential and pulmonary hypertension. Moreover, increases in plasma endothelin concentration have been reported as well in these disease states. When these observations are taken together, these states may be characterized by an attenuated release of EDRF, whereas the release of endothelin is augmented. An imbalance between EDRF and endothelin may contribute to the alteration in vascular tone characteristic of cardiovascular disease. The following review summarizes the present knowledge of the role of EDRF and endothelin in such disease processes. PMID- 1424047 TI - Mechanisms in intimal monocyte-macrophage recruitment. A special role for monocyte chemotactic protein-1. AB - This article briefly addresses the role of the monocyte-macrophage in atherogenesis and the potential mechanisms participating in intimal blood monocyte recruitment. The obligatory components of the recruitment process, i.e., contact with the vascular endothelium, attachment, and migration into the subendothelial space, are addressed with reference to the influence of blood flow, plasma proteins (particularly low density lipoprotein), and inflammatory mediators and cytokines. The potentially important role of monocyte chemotactic protein-1 in regulating monocyte recruitment in plaque pathogenesis is discussed. PMID- 1424048 TI - von Willebrand factor as a target for antithrombotic intervention. AB - The adhesive protein von Willebrand factor is essential for the formation of platelet thrombi under flow conditions characterized by high shear stress. This function requires the interaction with two distinct platelet receptors, the glycoprotein complexes Ib-IX-V and IIb-IIIa. Interaction with the former results in platelet activation, a necessary step for binding to the latter and supporting stable aggregation. The inhibition of von Willebrand factor binding to glycoprotein Ib can be achieved with small recombinant fragments containing the specific functional domain of the molecule that interacts with this platelet receptor. Such fragments may provide a new selective approach to antithrombotic therapy. PMID- 1424049 TI - Why do plaques rupture? AB - Rupture of the plaque surface, often with thrombosis superimposed, occurs frequently during the evolution of coronary atherosclerotic lesions. It is probably the most important mechanism underlying the sudden, rapid plaque progression responsible for acute coronary syndromes. The risk of plaque rupture depends on plaque type (composition) rather than plaque size (volume), because only plaques rich in soft extracellular lipids are vulnerable (rupture-prone). Most ruptures are tiny, occurring at the periphery of the fibrous cap that covers the lipid-rich core--points where the cap is usually thinnest and most heavily infiltrated by macrophage foam cells. Compared with intact caps, ruptured ones usually have less tensile strength and are more extensible, containing less collagen and glycosaminoglycans, more extracellular lipid, fewer smooth muscle cells, and more macrophages. Progressive extracellular lipid accumulation (lipid core formation) and cap weakening (macrophage related?) predispose the plaque to rupture and determine the actual vulnerability, which may change with time. Luckily, the plaque components responsible for vulnerability (soft lipid and probably macrophages) are apparently most likely to regress with treatment. The dynamic interplay between the actual plaque vulnerability and external stresses ("triggers") probably determines the particular moment and point of rupture, if this occurs. Vulnerability probably plays a more important role in rupture than triggers, because exercise stress testing of patients with advanced coronary artery disease rarely triggers a rupture/thrombus-related acute heart attack. A prerequisite is the presence of a vulnerable plaque. PMID- 1424050 TI - Factors controlling the development of arterial lesions after injury. AB - This review discusses the role of growth factors on the proliferation of smooth muscle cells (SMCs) in injured arteries. We have used a variety of procedures to injure rat carotid arteries and noted that removal of endothelium followed by platelet adherence does not always initiate SMC replication. Furthermore, thrombocytopenia did not reduce the early SMC replication induced by balloon catheter injury. Platelet-derived growth factor (PDGF) has been found to exert little effect on SMC replication but markedly influences the ability of SMCs to migrate to the intima. Basic fibroblast growth factor (bFGF) is a potent mitogen for SMCs in denuded arteries while having no effect on cells in control uninjured arteries. We have hypothesized that arterial injury leads to release of bFGF from injured SMCs and so stimulates cell replication. Rats were treated with antibodies to bFGF immediately before balloon injury, and this significantly reduced the SMC replication. These findings suggest that in vivo bFGF is an important mitogen for initiating SMC replication and that PDGF is important as a chemotactic for SMCs. PMID- 1424051 TI - A cascade model for restenosis. A special case of atherosclerosis progression. AB - BACKGROUND: Restenosis presently limits the long-term success of percutaneous transluminal coronary angioplasty (PTCA) and allied treatments of atheroma. Current views of the pathophysiology of restenosis fail to explain certain important clinical features: Thrombosis, often invoked as a cause of smooth muscle proliferation, wanes before intimal thickening peaks. Prolonged antithrombotic therapy does not eliminate restenosis after PTCA. Furthermore, only a minority of angioplastied lesions develop clinically significant restenosis. METHODS AND RESULTS: We propose a cytokine-growth factor cascade mechanism of restenosis pathobiology that could explain these features of human restenosis. According to this model, PTCA would produce acute local thrombosis and/or mechanical injury that triggers cytokine/growth factor gene expression by resident macrophages and smooth muscle cells. This early acute generation of cytokines could evoke a secondary growth factor and cytokine response that might establish a positive, self-stimulatory autocrine and paracrine feedback loop that would serve to amplify and sustain the proliferative response. This multistage schema would account for the lag between injury and restenosis and the failure of chronic antithrombotic therapy to prevent this process. Human atheromata contain variable numbers of macrophages. The macrophage content of a particular lesion could determine in part propensity to develop restenosis after angioplasty, explaining why all lesions do not develop this process. CONCLUSIONS: Several experimental observations support this novel mechanistic model. Leukocytes and smooth muscle cells express genes for cytokines and growth factors, and products of coagulation and thrombosis can activate mononuclear phagocytes. Cytokines and growth factors often augment their own gene expression and induce one another, providing a potential intralesional amplification loop. Experimental atheroma and advanced human atherosclerotic lesions do not express high levels of growth stimulatory cytokines such as interleukin-1 or tumor necrosis factor in the basal state but exhibit inducible expression in response to an injurious stimulus. Thus, cascades of autocrine or paracrine mediators whose expression is triggered by vascular injury might contribute to deranged smooth muscle behavior during restenosis. PMID- 1424052 TI - Induction of PDGF-responsive genes in vascular smooth muscle. Implications for the early response to vessel injury. AB - Arterial injury induces vascular smooth muscle cells (VSMC) to modulate from a quiescent to a proliferative state characterized by cell division, migration, and secretion of matrix. These changes have been implicated in the development of intimal hyperplasia after balloon angioplasty. The transition of VSMC to a proliferative state is preceded by the accumulation of platelets and leukocytes, which may release growth factors and cytokines at the site of injury. Platelet derived growth factor (PDGF) is secreted by platelets and a variety of cellular elements associated with the vessel wall and, as a VSMC mitogen and chemoattractant, has been implicated in the pathogenesis of intimal hyperplasia. We have found that, in addition to its effects on VSMC growth and migration, PDGF induces the expression in VSMC of the JE and KC genes, which encode monocyte and neutrophil chemoattractants, respectively. The induction of JE and KC by PDGF in VSMC culture involves several distinct transmembrane signaling pathways. In addition to their induction in VSMC culture, JE and KC messenger RNA accumulates rapidly and transiently in adult rabbit aorta after balloon dilatation, suggesting a role for these chemoattractants in the early vascular response to injury in vivo. The VSMC may therefore play a dual role in vessel injury, both as a mediator of the inflammatory response through chemoattractant release and as an effector of the hyperplastic response through proliferation. PMID- 1424053 TI - Thrombus formation on ruptured atherosclerotic plaques and rethrombosis on evolving thrombi. AB - Angiography in patients with unstable angina or myocardial infarction with subtotal coronary occlusion often reveals eccentric stenoses with irregular borders, suggesting ruptured atherosclerotic plaques and thrombosis, as documented by angioscopy and at autopsy. We have simulated and studied these processes in an ex vivo perfusion chamber and in an in vivo swine model. Our results suggest that specific local factors at the time of plaque disruption influence the degree of thrombogenicity, the stability of the growing thrombus, and, therefore, possibly also the various clinical syndromes. These factors can be divided into two groups: local vessel wall-related factors and systemic factors with local action at the area of risk. These factors include the following. 1) Exposed substrate-related effects: Plaque rupture produces a rough surface and stimulates the development of occlusive thrombus in proportion to the degree of damage. 2) Fluid dynamics-related factors: The more severe the stenotic lesion after plaque rupture, the higher the local shear rate, resulting in enhanced platelet deposition and thrombus formation. 3) Vasoconstrictive effects: Vasospasm is an important contributor to the pathogenesis of ischemic heart disease. 4) Systemic factors: There is clinical and experimental evidence to suggest that various systemic factors at the time of plaque rupture may enhance thrombogenicity (i.e., levels of epinephrine, levels of serum cholesterol, impaired fibrinolysis). We have investigated the role of residual thrombus on the process of rethrombosis and found that a residual thrombus is a very thrombogenic surface that may significantly contribute to reocclusion even in heparinized blood. Using recombinant hirudin as a pharmacological tool in our flow studies, we observed that rethrombosis is partially caused by thrombin bound to fibrin in the original thrombus, because the effect is abolished by the specific thrombin inhibitor. PMID- 1424054 TI - Role of high density lipoproteins in the regression of atherosclerosis. AB - Atherosclerosis is a slowly progressive disease characterized by the accumulation of cholesterol within the vessel wall. Plasma lipoproteins are particles of complex lipid and protein composition that transport lipids in blood. Low density lipoproteins (LDL) and high density lipoproteins (HDL) are the major cholesterol carrier lipoproteins. LDL seem to be responsible for the delivery of lipids (cholesterol) from the liver to the tissues. Compelling evidence supports the concept that the lipids deposited in the arteriosclerotic lesions are derived primarily from plasma LDL. The term "reverse cholesterol transport" describes the transport of cholesterol from extrahepatic tissues to the liver, where it may be metabolized. Reverse cholesterol transport seems to be the major route for removal of the exchangeable cholesterol deposited in the extrahepatic tissue. It has been postulated that a major role of the plasma HDL particle is to act as a scavenger of tissue cholesterol. The hypothesis that high levels of plasma HDL are protective against coronary artery disease (CAD) was initially proposed by Barr et al in the early 1950s, but it was overlooked until confirmed by the Tromso and Framingham studies in 1977, which showed an inverse relation between HDL plasma levels and incidence of CAD. Similar observations have been made in 15 major experimental studies including eight countries.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424055 TI - The relation between atherosclerosis and thrombosis. AB - BACKGROUND: The relation between atherosclerosis and thrombosis has been recognized for over a century. Until very recently, however, this pathophysiological association has been largely based on observation with little information available to dissect molecular and cellular mechanism. METHODS AND RESULTS: The known associations between the principal determinants of thrombosis (platelets, fibrin and its proteolytic degradation products, and fibrinolytic enzymes) and atherosclerosis; the regulation of thrombotic determinants by cytokines and growth factors important in atherogenesis; and the modulation of thrombotic determinants by atherogenic lipoproteins, especially lipoprotein(a), are discussed. CONCLUSIONS: Within this conceptual framework, clear molecular and cellular mechanisms emerge, and a better basic understanding of the thrombotic determinants of atherogenesis can be developed. PMID- 1424056 TI - A retrospective study of disposable extended wear lenses in 100 patients: year 2. AB - We present the results of the second year of follow-up of 100 patients wearing disposable contact lenses on an extended wear basis. Thirty-seven males and 63 females participated in the study (mean age: 41.1 years +/- 13.88 (mean +/- 1 standard deviation); and the mean patient follow-up time was 26 months +/- 4.9). A total of 13 patients were lost to follow-up. Seventeen patients discontinued extended wear yet continued to wear soft lenses on a daily wear basis--the reasons for this finding are discussed. A significant decrease in the number of events defined as complications (32 events) was noted when compared to the first year of follow-up (136 events). Seven corneal infiltrates occurred during the second year, compared to 6 such events during the first year of the study. Additional complications included: giant papillary conjunctivitis (6 cases), corneal staining (5 cases), and corneal abrasions (4 cases). Disposable extended wear soft contact lenses offer a reasonable means of vision correction in the properly selected patient. At the same time, caution should be exercised in the fitting and wear of these lenses. PMID- 1424058 TI - A clinical evaluation of two multifocal soft contact lenses. AB - We fit two multifocal soft contact lenses, Bausch & Lomb's Bi-Tech and the Unilens contact lens from Unilens Corporation, in two separate populations of presbyopes. Most patients (24/42, 57%) had no prior contact lens experience. Patients were evaluated at 6 and 12 months for comfort, visual acuity, lens fit, and corneal findings. Both distance and near vision were found to be slightly decreased with each contact lens when compared to best corrected visual acuity with spectacles. Seventy-seven percent (14/18) of the Unilens wearers and 67% (16/24) of the Bi-Tech wearers continued to wear their lenses for at least 1 year. Those who discontinued lens wear did so because they were dissatisfied with their vision. Presbyopes who seek correction with soft contact lenses appear to be more tolerant of a decrease in distance vision than a decrease in near vision. Both lenses were comfortable and no corneal pathology was induced. Our results suggest that the Unilens (simultaneous vision design) provides more predictable correction of presbyopic symptoms than the Bi-Tech (alternating vision design) because it is independent of lower lid position and translation. Both of these lenses are viable options for the correction of presbyopic symptoms. PMID- 1424057 TI - A European fitting philosophy for aspheric, high-Dk RGP contact lenses. AB - Microbial keratitis, the most serious complication of contact lens wear, is most frequently associated with soft contact lenses. Rigid gas permeable (RGP) lens wearers are less often affected. Increased use of high-Dk RGP lenses could reduce the number of cases of microbial keratitis. In Europe, aspheric high-Dk RGP lenses are very popular. This article presents practical guidelines for computer aided fitting of aspheric RGP lenses. Base curve selection using the keratometer to determine the corneal topography is described. This method, which is inexpensive and time-saving, is suitable for fitting cosmetic contact lenses or lenses used in treating such corneal pathology as keratoconus. PMID- 1424059 TI - Microbial contamination of hydrophilic contact lenses. Part II: Quantitation of microbes after patient handling and after aseptic removal from the eye. AB - We cultured Soflens (polymacon) contact lenses to determine the number of microorganisms present after patient handling and the number present after patient handling and 5 hours of lens wear. Twenty adapted contact lens patients were each dispensed two pairs of new sterile Soflens contact lenses. Both pairs of lenses were handled by the patients during a single experimental session. Prior to handling lenses, patients were instructed to wash their hands with soap and water, rinse with tap water, and dry with a paper towel. One pair (handled only) was cultured immediately after handling. The second pair (handled-and-worn) was placed on the eyes by the patient, removed aseptically following 5 hours of wear, and then cultured. All 40 handled-only lenses had viable microorganisms associated with them (mean: 653 colony forming units (CFU) per lens). Bacteria were isolated on all of these lenses and fungi were detected on six. The mean bacterial count for the handled-and-worn lenses was 30 CFU/lens; fewer than half exhibited handled-and-worn lenses was 30 CFU/lens; fewer than half exhibited bacteria and no fungi were isolated. These data suggest that patient handling is a highly significant source of microbial contamination of hydrophilic contact lenses. Also, the number of microorganisms on lenses is significantly reduced (P < 0.0001) after the lens has been worn on the eye. PMID- 1424060 TI - Collagen shields containing tobramycin for sustained therapy (24 hours) of experimental Pseudomonas keratitis. AB - We compared collagen shields hydrated in 1.36% tobramycin with topical 1.36% tobramycin for sustained treatment of experimental Pseudomonas keratitis in rabbits. Antibiotic therapy for a total of 24 hours was initiated 14 hours after an intrastromal injection of 10(3) logarithmic phase Pseudomonas aeruginosa. Seven groups were treated as follows: groups 1-3, collagen shields hydrated in tobramycin supplemented with topical 1.36% tobramycin drops at 4, 6, or 8 hour intervals; group 4, collagen shields hydrated in tobramycin without any further topical supplementation; group 5, topical tobramycin therapy, initially every half-hour for 4 hours, then hourly; group 6, collagen shields hydrated in balanced saline solution; and group 7, no treatment. Each group contained four eyes. The groups treated with collagen shields supplemented every 4 or 6 hours with topical tobramycin had significantly fewer colony forming units (CFU) than those receiving topical or collagen shield therapy alone (P < 0.001). The group treated with collagen shields hydrated in sterile saline had 10(7) CFU per cornea, which was not significantly different from the untreated group (P > 0.2). Collagen shields hydrated in tobramycin and supplemented with topical tobramycin were effective in sustained treatment of experimental Pseudomonas keratitis. PMID- 1424061 TI - Practical aspects of a corneal topography system. AB - We used the EyeSys Corneal Topography System to examine several issues relating to corneal topography systems and the interpretation of their results. Interferometry measurements of EyeSys calibration spheres indicated that they deviated from suggested values by 0.05 +/- 0.13 D (mean +/- 1 standard deviation). The EyeSys unit reliably determined the calibration spheres to be spherical with differences between the flat and steep axis of 0.10 +/- 0.09 D. The data for the 3 mm chord circle was the least reliable. The spherical equivalent values for the calibration spheres were constantly greater than the 0.25 D reproducibility suggested by the manufacturer. Furthermore, the precision of the outputted values (0.01 D) is beyond the capability of the instrument. This gives the impression that the topography unit cannot consistently reproduce measurements of the calibration objects or chrome plated steel spheres. Image centralization and focus were found to be critical in obtaining accurate results. A target off center by more than 0.25 mm resulted in unreliable data; increasing the focal distance by greater than 1 mm beyond the focal point resulted in a sharp decrease in accuracy (a decrease in the focal distance was even more critical). When measuring aspheric contact lenses, it was found that the keratometer and EyeSys unit provided a close approximation of the surface characteristics of the lenses. A realistic view of the limitations of the topography system being used is critical for proper interpretation of the data. PMID- 1424062 TI - The effect of pregnancy on corneal curvature. AB - Even though they had been successful contact lens wearers previously, many women develop contact lens intolerance while pregnant. We prospectively followed 24 women during pregnancy, postpartum, and after cessation of breastfeeding. Six women (25%) developed contact lens intolerance during the study period. There were no changes observed in refraction, corneal sensitivity, corneal thickness, or intraocular pressure. However, there was a statistically significant (P < 0.05) increase in corneal curvature during the second and third trimester which resolved postpartum or after the cessation of breastfeeding. We discuss the clinical importance of this finding. PMID- 1424063 TI - A quantitative method for LDH, MDH and albumin levels in tears with ocular surface toxicity scored by Draize criteria in rabbit eyes. AB - We have established a quantitative method for evaluation of ocular surface lesions on the basis of lactate dehydrogenase (LDH) activity, malate dehydrogenase (MDH) activity, and albumin levels in rabbit tears. Lesions were produced with solutions of 0.005-0.02% benzalkonium chloride (BAK), 0.01-0.03% chlorhexidine digluconate (CHX), and 0.01-0.03% polyhexamethylene biguanide hydrochloride (PHMB), all of which are widely used in topical ophthalmic preparations. Two drops of test solution were instilled 15 times into rabbit eyes at 5 minute intervals. Sixty minutes after 0.02% BAK instillation, tear LDH activity increased from 1,840 U/L (without instillation) to 26,100 U/L, and concomitantly tear albumin levels rose from 0.11 mg/mL (without instillation) to 9.48 mg/mL. Instillation of 0.03% CHX and 0.03% PHMB caused smaller increases in LDH and MDH activity and albumin tear levels. LDH activity and albumin levels in tears were significantly correlated with the degree of total ocular surface lesions in both cornea and conjunctiva as observed by slit lamp biomicroscopy quantified using a modified Draize score. Based on the results of this study, we believe that LDH activity and albumin level in tears can be used as objective indicators for the quantitative evaluation of ocular surface lesions on both cornea and conjunctiva following application of topical ophthalmic preparations containing cytotoxic preservatives in animals and man. PMID- 1424064 TI - Everett Kinsey Lecture. The enigma of the corneal contour. PMID- 1424065 TI - New technology in the catheterization lab. PMID- 1424066 TI - A checklist of common oral manifestations of HIV infection. PMID- 1424067 TI - Risk factors for HIV infection in homosexual men: the Cleveland men's study of risks in a low-prevalence area. AB - Detailed questionnaires concerning alcohol and drug use, sexual practices, and medical history were completed by 301 homosexual men living in the Cleveland metropolitan area. Their sera were subsequently tested for antibodies to the human immunodeficiency virus. Fifty-six (18.6%) were seropositive. In a univariate analysis, age, drug use, and four specific sexual practices were associated with seropositivity. In a multiple logistic regression analysis, intravenous drug use and receptive anal-genital sex remained independent predictors of seropositivity. PMID- 1424068 TI - Ordering respiratory care services for hospitalized patients: practices of overuse and underuse. AB - Because of recent concerns about misallocation of respiratory care services and analyses suggesting that limiting services to comply with established guidelines reduces unneeded therapies without compromising quality of care, the authors audited the records of 170 patients newly ordered to receive at least one of five respiratory therapies (oxygen therapy, incentive spirometry, bronchopulmonary hygiene, aerosolized bronchodilator therapy, or intermittent positive pressure breathing) at The Cleveland Clinic Foundation. In reviewing whether the therapies that were ordered complied with published guidelines for these services, we found that 25.2% were "not indicated." This over-ordering incurred unnecessary total charges of $11,937 ($206.16 per patient) and occupied therapist time that could have been better allocated to other services. These costs were offset by the finding that 10.5% of the patients were not ordered to receive indicated respiratory therapies. Our proposed strategy of initiating protocols for ordering and providing respiratory care services (ie, via a respiratory care consult service) is an appealing means to address this misallocation, but it requires further evaluation. PMID- 1424069 TI - Adults with congenital complete heart block: 25-year follow-up. AB - Complete congenital heart block has been recognized since 1846, yet the prognosis of the disease has not been determined by comprehensive long-term studies. We reviewed 14 cases of complete congenital heart block at The Cleveland Clinic Foundation. The patients were followed for a mean of 25 years (range, 20 to 32 years). Ten patients had structurally normal hearts, and 4 had varying degrees of congenital heart disease. The patients were evaluated with regard to symptoms, and indications for permanent pacemaker implantation were studied. Seven patients received permanent pacemakers. Ages at the time of pacemaker implantation ranged from 15 to 38 years (mean, 25 years). Overall, the patients in our study tended to lead normal productive lives. The main indications for pacemaker implantation were symptoms alone. Guidelines for prophylactic pacemaker implantation have yet to be determined, and the development of these guidelines is difficult due to small numbers of patients at isolated centers. A large international study is needed to set these guidelines. PMID- 1424070 TI - The effect of do-not-resuscitate orders on length of stay. AB - In 1988, a new do-not-resuscitate policy aimed at assisting professional staff, nurses, patients, and families in end-of-life choices replaced the existing policy at The Cleveland Clinic Foundation. We conducted a retrospective chart review to examine the effects of the new policy on length of stay. Data were collected on demographics, clinical information, length of stay, and the frequency of do-not-resuscitate orders for expired Medicare patients in 1987 (n = 125) and 1989 (n = 135). Length of stay for patients who received a do-not resuscitate order was significantly reduced in 1989 compared with 1987, partly because the orders were issued earlier in patients' stays in 1989. The number of days from writing the order until death did not change significantly from 1987 to 1989. We conclude that a well-defined do-not-resuscitate policy can reduce length of stay. PMID- 1424071 TI - Adjuvant therapy for colorectal cancer. AB - The search for effective adjuvant therapy for colorectal cancer has been long and, until recently, largely unrewarding. Surgery alone is inadequate therapy in as many as 50% of patients. But recent studies demonstrate significant improvement in disease-free survival and overall survival for patients with advanced colon and rectal cancer who receive adjuvant therapy. Postoperative chemotherapy with fluorouracil and levamisole is the standard of care for patients with stage III colon cancer, and postoperative high-dose pelvic radiation combined with fluorouracil is the standard regimen for patients with stage II and III rectal cancer. PMID- 1424072 TI - New strategies in nonantibiotic treatment of gram-negative sepsis. AB - Gram-negative bacterial infections are difficult to control and often lead to septic shock or septic syndrome. Many physiologic changes in sepsis are due to bacterial triggering of host responses. Improved understanding of these mechanisms has led to new treatment modalities that aim to block the runaway inflammatory process of sepsis. New therapeutic agents are currently being evaluated in animal and human studies. By combining these advances with adequate antibiotic therapy, it may be possible to improve overall survival in patients with gram-negative sepsis. PMID- 1424073 TI - Cytokines and the pathogenesis of insulin-dependent diabetes mellitus. AB - Insulin-dependent diabetes mellitus is an autoimmune phenomenon in humans. At onset, the diabetic pancreas shows a well-characterized insulitis. The inflammatory cells are specifically directed toward beta cells of the pancreatic islets. Several hypotheses link genetic susceptibility for diabetes to immunologic mechanisms. The cytokines interferon gamma and interleukin-6 have essential roles in the progressive destruction of beta cells. Studies with experimental models may improve definition of the pathogenesis of insulin dependent diabetes mellitus. Combining genetic studies that detect susceptibility to insulin-dependent diabetes mellitus with future therapies aimed at interrupting cytokine production or cytokine receptor expression may lead to prevention of insulin-dependent diabetes mellitus. PMID- 1424074 TI - The effect of sleep position on the diagnosis of obstructive sleep apnea: a word of caution. AB - Sleeping in the supine position exacerbates obstructive sleep apnea. Patients sleeping off their backs during a polysomnographic study might have a normal study in spite of having a history of severe obstructive sleep apnea. This might be shown by repeating the study with the patients spending most of the study time sleeping on their backs. We report three patients illustrating this point and discuss the importance of monitoring sleep position while performing polysomnography. The effect of position in interpreting different therapeutic modes for obstructive sleep apnea should be considered. PMID- 1424075 TI - Renal pseudoenlargement secondary to retroperitoneal liposarcoma. AB - A case of renal pseudoenlargement caused by a large retroperitoneal mass is reported. An intravenous urogram showed apparent enlargement of the right kidney and a normal left kidney. Computed tomography showed a normal-sized right kidney. The discrepancy was due to magnification produced by marked anterior displacement of the right kidney by a retroperitoneal liposarcoma. PMID- 1424076 TI - Syndrome of inappropriate secretion of antidiuretic hormone after infusional vincristine. AB - A 77-year-old woman with refractory multiple myeloma was treated with a 4-day continuous intravenous infusion of vincristine and doxorubicin and 4 days of oral dexamethasone. Nine days after her second cycle she presented with lethargy and weakness associated with hyponatremia. Evaluation revealed the syndrome of inappropriate secretion of antidiuretic hormone, which was attributed to the vincristine infusion. After normal serum sodium levels returned, further doxorubicin and dexamethasone chemotherapy without vincristine did not produce this complication. PMID- 1424077 TI - Squamous cell carcinoma of the bladder in a patient on intermittent self catheterization. AB - Squamous cell carcinoma of the bladder has been associated with exstrophy, defunctionalized bladders, chronic infection, cystolithiasis, and chronic indwelling catheters. We report a case of squamous cell carcinoma of the bladder in a woman performing intermittent self-catheterization for the previous 14 years. PMID- 1424078 TI - Obstacles to HIV prevention. PMID- 1424079 TI - Clinical ethics and cost containment: promises and pitfalls. PMID- 1424080 TI - Expansile tibial lesion in a 23-year-old man. PMID- 1424081 TI - Immunoreactive vasotocin in the zebra finch brain (Taeniopygia guttata). AB - The distribution of vasotocin (VT)-immunoreactive cells and fibers in the zebra finch brain was studied with immunocytochemical techniques. A large number of VT immunoreactive cells was found in the nucleus preopticus anterior and nucleus paraventricularis. In the lateral parts of the hypothalamus diffusely organized VT-immunoreactive cells were present. Some of these cells were found close to and embedded in the optic tract. An extra-hypothalamic parvocellular cell group was found at the level of the anterior commissure in the dorsal diencephalon. VT immunoreactive fibers and varicosities were present in a number of extrahypothalamic regions i.e. the septum, the area ventralis of Tsai, the lateral habenula, the optic tectum, the substantia grisea centralis, the nucleus tractus solitarii, the lateral medulla, the nucleus intercollicularis and in the archistriatum surrounding the nucleus robustus archistriatalis. The VT immunostaining in the lateral septum and dorsal diencephalon showed no sex differences and can not be influenced by testosterone administration. IN CONCLUSION: the topography of the central VT-immunoreactive network is similar to that in another song bird i.e. the canary; but seasonal and testosterone dependent changes in VT-immunostaining in the lateral septum and dorsal diencephalon are only observed in the canary. PMID- 1424082 TI - Large serotonin-like immunoreactive amacrine cells in the retina of developing Xenopus laevis. AB - The earliest appearance of serotonin-like immunoreactivity (SLI) in different cell types and the development of large SLI amacrine cells were studied in the retina of Xenopus laevis from stage 33/34 to adult. Intense SLI was first found in the somas of large amacrine cells at stage 39. The somas of small amacrine cells showed weak SLI at stage 41, followed by bipolar cells at stage 43. The number of large SLI amacrine cells in the inner nuclear layer of the retina increased from 57 at stage 40 to 774 in adult. Over the same period, retinal area increased from 0.19 mm2 to 24.57 mm2 with an accompanying decrease of cell density from 301/mm2 to 32/mm2. in adult animals large SLI amacrine cells were non-uniformly distributed. Peak cell density of 50-60/mm2 was located in the center of the ventrotemporal quadrant and a trough of 8-15/mm2 in the dorsal periphery of the retina. Peak cell density region of the adult retina corresponded to part of the retina formed at early developmental stages where the rate of cell generation of large SLI amacrine cells was higher. These observations indicate that (1) SLI is expressed first by large amacrine cells, followed by small amacrine and bipolar cells; (2) large SLI amacrine cells are generated continuously throughout life, (3) the non-uniform retinal distribution of large cells results from a spatio-temporally differential cell generation at the ciliary margin. PMID- 1424083 TI - Brain grafts of migratory GnRH cells induce gonadal recovery in hypogonadal (hpg) mice. AB - Gonadotropin-releasing hormone (GnRH) neurons are derived from the olfactory placode and migrate into the CNS during embryogenesis. During this migration the GnRH neuronal population follows a very specific pathway through the nasal septum and forebrain with individual neurons 'stopping' at various points along the way. Following migration GnRH neurons elaborate axonal projections, the major one to the median eminence. The function of this neurosecretory connection can then be assessed by activation of the pituitary-gonadal axis. In previous experiments we had demonstrated that grafted post-migratory GnRH neurons could send axons to the median eminence and initiate gonadal development in hypogonadal (hpg) mice that lack GnRH. In the present experiment, grafts derived from the embryonic nasal septum, which contains the migratory population of GnRH neurons, were used to determine if the transplanted GnRH neurons could (1) continue their migration in the adult host brain, (2) elaborate axons to their normal target in the host and (3) stimulate the host pituitary-gonadal axis to induce gonadal development. Nasal tissue from normal mouse embryos was implanted into the preoptic area (n = 8), anterior hypothalamus (n = 3) or third ventricle (n = 1) of adult hpg males. Following survival of 10 days to 10 weeks, the distribution of GnRH immunoreactive elements was assessed and testicular weight recorded. Surviving GnRH neurons were few in number and were found within the graft (n = 3), the host brain (n = 2) or both (n = 1). Four grafts resulted in specific outgrowth of GnRH axons through the host parenchyma to the median eminence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424084 TI - Alterations of nerve-muscle interaction during postnatal development influence motoneurone survival in rats. AB - The effect of temporary paralysis of rat soleus muscles shortly after birth on motoneurone survival was studied using retrograde labelling with HRP. Following a single application of alpha-bungarotoxin (alpha-BTX) at birth the muscles were paralysed for 24-48 h. The number of HRP-labelled motoneurones in the treated ventral horn of the spinal cord in 10-week-old rats decreased to 63.7% (+/- 2.7 S.E.M.) of the control ventral horn. This motoneurone loss occurs relatively late after alpha-BTX application, for in animals examined at 3-4 weeks of age, the number of labelled motoneurones in the treated ventral horn was not reduced. When paralysis of the soleus muscles was extended to 6-8 days by application of an additional alpha-BTX implant, then by 10 weeks of age only 34.7% (+/- 1.5 S.E.M.) of soleus motoneurones were present. Thus, prolonging the duration of paralysis reduced the number of surviving motoneurones. Furthermore, the mean area of motoneurones that survived alpha-BTX treatment was smaller than that of controls. There was also a shift in the size distribution of the motoneurones in that there was a relative increase in the proportion of small motoneurones. This finding is similar to observations on motoneurone sizes after neonatal nerve injury. Thus, interruption of neuromuscular interaction during early postnatal development causes many motoneurones to die, and in addition alters the size distribution of the remaining cells. PMID- 1424085 TI - A molecular recognizing system of serotonin in rat fetal axonal growth cones: uptake and high affinity binding. AB - Axonal growth cone particles (AGCP) isolated from prenatal and postnatal rat brain had different high-affinity 5-HT uptake characteristics. In postnatal AGCP the uptake behaves as in the adult rat brain, while in the prenatal AGCP the uptake characteristics seem to be in a transitional stage. Also in prenatal AGCP we observed specific, high-affinity 5-HT binding sites. These results support the idea of an important role for 5-HT during axogenesis. PMID- 1424086 TI - Hyperactivity and altered amphetamine sensitivity in premature juvenile rats. AB - 'Premature' rats that were delivered by cesarean section on day 21 of gestation and 'normal' rats that were delivered spontaneously on day 22 of gestation were tested for basal locomotor activity and locomotor stimulation in response to D amphetamine at 19-21 days of age. Compared to normal rats, premature rats had increased basal levels of locomotor activity and showed enhanced sensitivity to the locomotor stimulant effects of D-amphetamine. Cesarean-delivered premature rats may be a useful animal model for investigating mechanisms of neurobehavioral deficits associated with premature birth in humans. PMID- 1424087 TI - Serotonin 1B receptors form a transient vibrissa-related pattern in the primary somatosensory cortex of the developing rat. AB - Serotonin (5-HT)-immunoreactive axons have a patterned distribution in the primary sensory cortices of developing rodents. This distribution becomes apparent shortly after birth and disappears around the end of the second postnatal week. We employed binding of [125I]cyanopindolol in the presence of isoproterenol to determine whether 5-HT1B receptors have a similar transient spatiotemporal distribution. In rats killed on postnatal day (P-) 8, 5-HT1B receptors have a distribution closely matching that of 5-HT-immunoreactivity. The receptors are very dense in lamina IV of both the primary visual and somatosensory cortices and, like 5-HT immunoreactive axons within the somatosensory cortex, form patches matching the distribution of the mystacial vibrissae. In adult animals, the density of these receptors in lamina IV and the supragranular layers of the visual and somatosensory cortices is reduced relative to that in the surrounding cortex. Autoradiograms of the flattened cortices of adult rats yield a 'negative image' of the pattern observed in perinatal animals. Thus, one subclass of 5-HT receptors, the 5-HT1B receptor, has a spatial distribution in cortex which changes in development much like that for serotoninergic axons. PMID- 1424088 TI - Aging reverts to juvenile conditions the synaptic connectivity of cerebral cortical pyramidal shafts. AB - Quantitative analysis of the total number and distribution of dendritic spines along the apical shafts of layer V cerebral cortical pyramids has been performed on aging rats (90-120 to 1,135 days old) and on rats during the period of early and late development (10-80 days). As expected from previous work, present results show that the total number of dendritic spines along the shafts increase from 10 to 80 days, after which it starts to gradually decrease until the last age studied (1,135 days). The quantitative analysis of the effect of aging on the relative decrease of dendritic spines shows that this decrease starts being homogeneous along the whole length of the apical shafts and that from a certain age onwards, estimated according to present results in 400 days, this effect is significantly more pronounced in layers IV and III-II than in deep layers. Furthermore, the comparison made between the distribution of dendritic spines along the apical shafts of pyramidal neurons of old and young animals has shown that aging produces a regression of this distribution to juvenile conditions. PMID- 1424089 TI - Effect of cocaine, ethanol or nicotine on ornithine decarboxylase activity in early chick embryo brain. AB - Fetal drug exposure causes multiple deficits in the developing child. For both humans and animal models, the single most common drug-related problem is fetal growth suppression. This defect is associated with significant perinatal morbidity and mortality and may also be related to significant behavioral problems appearing later in life. Studies focussed on the molecular mechanism of fetal drug effects in placental models are complicated by multiple interactions of the drug with mother, placenta and fetus. Using early (76-168 h) chick embryos as a non-placental model, and three common drugs of abuse (nicotine, ethanol and cocaine) it was found that each drug suppressed the peak in fetal brain ornithine decarboxylase (ODC) activity that normally occurs at 120 h of development. For each drug, the decrease in ODC activity at 120 h was followed by a small but significant increase in ODC. Thus, although the drug-treated embryos were smaller in size, they appeared to be undergoing compensatory growth and, in fact, became equal in weight to the vehicle-treated animals, if allowed to hatch. PMID- 1424091 TI - Interendothelial junctions during blood-brain barrier development in the rat: morphological changes at the level of individual tight junctional contacts. AB - The endothelium of brain capillaries represents the structural basis for the blood-brain barrier in vertebrates. Individual endothelial cells are linked by a continuous belt of complex tight junctions (zonulae occludentes). Hydrophilic solutes and macromolecules are believed to cross the barrier through specific carrier mechanisms. Unspecific paracellular ionic leak is thought to be very low. In rats the blood-brain barrier is not fully developed until postnatal day 24. We investigated the ultrastructure of the developing blood-brain barrier at 5 developmental stages between embryonic day 17 and young adults. The use of high power goniometric tilting of ultrathin sections allows one to gather information about the exact relationship between two opposing membranes throughout the entire length of the cleft. Our results suggest that the maturation of blood--brain barrier interendothelial clefts is accompanied by the establishment of a characteristic ratio of 'narrow zone' (complex tight junctions) to 'wide zone' (15-20 nm), and of a typical cleft length. Membrane separation larger than 20 nm disappear and individual tight junctional contacts undergo structural changes. PMID- 1424090 TI - Development of cerebral arterial innervation: synchronous development of neuropeptide Y (NPY)- and vasoactive intestinal polypeptide (VIP)-containing fibers and some observations on growth cones. AB - The pre- and postnatal development of sympathetic fibers containing neuropeptide Y (NPY) and parasympathetic fibers containing vasoactive intestinal polypeptide (VIP) supplying the cerebral arteries were studied with immunohistochemistry in rats. The innervation patterns and densities of NPY and VIP fibers were similar at all stages of development and similar to that previously reported for norepinephrine (NE). There was a striking reorganization of the innervation pattern of all three fiber systems between the first and second postnatal weeks. At all stages of development prior to the first postnatal week, growth cones were present on individual fibers at the distal part of major cerebral arteries and the middle segment of the basilar artery. The growth cones had a range of shapes from blunt to stellate, lanceolate or filiform. NPY and VIP immunoreactive granules were commonly present. The present results taken with our earlier developmental study of NE fibers (J. Comp. Neurol., 271 (1988) 435-444), demonstrate that: (1) both sympathetic and parasympathetic perivascular nerves on immature cerebral vessels develop with similar sequences: first longitudinal fibers and fiber bundles are present; these transform to a meshwork pattern and finally transform again into the mature, predominantly circumferential pattern; (2) both the classical (NE) and peptidergic transmitters (NPY) within the sympathetic system appear to develop identically in terms of time of appearance, innervation patterns, densities and reorganization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424092 TI - Axotomized frog sciatic nerve releases diffusible neurite-promoting factors. AB - Using the bullfrog (Rana catesbeiana) dorsal root ganglia (DRG) and its sciatic nerve (ScN) as a model system, we have previously described neuronal and non neuronal molecular changes associated with the early regenerative response of DRG neurons to axotomy. Since diffusible molecular factors, released by axotomized ScN, might function to stimulate axon regrowth, we have assayed the ability of ScN-conditioned bath to promote in vitro neurite outgrowth from PC-12 cells. Diffusible ScN proteins were collected by incubating segments of normal or axotomized ScN in a small volume of RPMI media for 4 h (nerve bath). The nerve baths, supplemented with serum, were then added to PC-12 cell cultures to assay for the presence of neurite growth factors released by ScN. Results showed that nerve baths, collected from sham-operated or axotomized ScN, could not induce the differentiation of PC-12 into neurite-bearing cells. Therefore, in all subsequent neurite growth assay experiments, an exogenous source of nerve growth factor (NGF) (50 ng/ml) was added to the nerve baths or unconditioned media to generate and maintain PC-12 neuritic structure. We found that nerve baths, collected from previously axotomized (at least 3 days post-injury) nerve, contained diffusible factors which enhanced PC-12 neurite growth, relative to unconditioned media. No neurite growth factors were observed to be released by sham-operated ScN or 1-day post-axotomized ScN. Further experiments were conducted to identify the diffusible neurite growth factors released from axotomized ScN. We showed that the release (if any) of endogenous diffusible NGF or laminin from axotomized nerve could not have accounted for the facilitation of neurite growth. Analysis of radiolabelled ScN proteins by two-dimensional polyacrylamide gel could not have accounted for the facilitation of neurite growth. Analysis of radiolabelled ScN proteins by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) showed that the relative abundance of two diffusible proteins (M(r) approximately 35 and 70 kDa) in the nerve bath was directly correlated with the ability of the nerve bath to facilitate PC-12 neurite growth. PMID- 1424093 TI - A PCR analysis of rhodopsin gene transcription in rat pineal photoreceptor differentiation. AB - A polymerase chain reaction (PCR) method was used to detect rhodopsin transcripts in rat pineals both in vivo and in vitro. Only very low levels of transcripts were detected in preparations from adult rat pineal tissue, but fairly large amounts were detected in cDNA preparations from cultures of newborn rat pineals. The transcript level was reduced significantly if the cells had been cultured in the presence of 10 microM norepinephrine (NE). This concentration of NE had previously been shown to abolish almost completely the rhodopsin immunoreactivity normally seen in such cultures. The present work indicates that part, but not all, of the effect of NE is probably at the level of translation. PMID- 1424094 TI - Thyrotropin releasing hormone (TRH) and its analog, RGH-2202, accelerate maturation of cerebellar neurons in vitro. AB - We have studied the "trophic" action of thyrotropin releasing hormone (TRH) in cultured cerebellar granule cells, a pure and homogeneous population of glutamatergic neurons. As an index of neuronal maturation, we have measured the uptake of D-[3H]aspartate (a non-metabolizable analog of glutamate) at different days of maturation in vitro (DIV). In control cultures, D-[3H]Aspartate increased linearly during maturation reaching plateau values between 7 and 9 DIV; daily addition of TRH tartrate (TRH-t) or RGH-2202 (a TRH analog) accelerated in a concentration-dependent manner the maturation profile of D-[3H]aspartate uptake. This effect was more pronounced for RGH-2202: in cultures treated daily with RGH 2202, D-[3H]aspartate uptake was fully expressed after 3 DIV. Neither TRH-t nor RGH-2202 significantly increased D-[3H]aspartate uptake in mature cells, excluding a direct action on the glutamate transport system. Both compounds specifically potentiated the increase in [3H]inositol monophosphate formation (but not the stimulation of 45Ca2+ influx) induced by N-methyl-D-aspartate (NMDA) receptor agonists, without affecting the stimulation of inositol phospholipid hydrolysis by quisqualate or carbamylcholine. We suggest that, in cultured cerebellar granule cells, TRH and RGH-2202 enhance the trophic action of endogenous glutamate by amplifying some of the intracellular events that follow the influx of extracellular Ca2+ through NMDA-gated ion channels. PMID- 1424095 TI - Sex differences in cortical thickness and the dendritic tree in the monocular and binocular subfields of the rat visual cortex at weaning age. AB - The visual cortex of adult rats is sexually dimorphic at both the gross size and dendritic levels [Brain Res., 295 (1984) 27-34; J. Comp. Neurol., in press]. In addition, sex differences in the dendritic tree are dynamic and can be altered by environmental conditions imposed at weaning [Brain Res., 295 (1984) 27-34]. The present study examines sex differences in cortical thickness and in the dendritic tree of the monocular (Oc1M) and binocular (Oc1B) subfields in littermate male and female pairs of Long-Evans rats at weaning age (25 days). From Nissl-stained tissue, it was found that the whole cortex and layer II-IV of Oc1B was thicker in males than females. No sex differences were found in the thickness of Oc1M. Golgi Cox-stained pyramidal neurons in layer III from the Oc1M and Oc1B regions were quantified in 7 littermate pairs of weaning-age rats. There were no sex differences in the basilar tree, while the apical oblique branches were sexually dimorphic, especially in the monocular region. Females had greater total dendritic length and longer terminal branches in Oc1M compared to males. Females also had longer bifurcating branches in both Oc1M and Oc1B than males. The present study found that sex differences at weaning age do not completely mirror the dimorphisms found in the visual cortex of the adult rat. This study also indicates that related subfields can differ in their morphology and should be examined separately. PMID- 1424096 TI - Laminin selectively enhances axonal growth and accelerates the development of polarity by hippocampal neurons in culture. AB - We have examined the effects of laminin on the morphological development of embryonic rat hippocampal neurons maintained in tissue culture. Forty-eight hours after plating, neurons grown on a polylysine-coated substrate had become polarized, typically having one long axon and 4 or 5 minor processes. Adsorption of laminin to the substrate did not cause changes in the number of axons extended by hippocampal neurons but did cause significant increases in the length of the axonal plexus and in axonal branching. In contrast to its effects on axons, laminin did not influence the number, length, or branching of the minor processes that eventually become dendrites or the morphology of definite dendrites as assessed after 7 days in culture. In addition to selectively enhancing axonal growth, laminin greatly increased the rate of polarization of hippocampal neurons such that most became polarized within 18 h. Analysis of the time course of laminin's effects revealed that the acceleration of polarization was not associated with a change in the time of initial process formation, but rather with a selective stimulation of the growth of the longest process at all times from the 12th through the 48th h in vitro. These data suggest that even though the basic shape of hippocampal neurons may be intrinsically programmed, critical aspects of their morphological development may be modulated by extracellular matrix molecules such as laminin. PMID- 1424097 TI - Alterations in septohippocampal cholinergic innervations and related behaviors after early exposure to heroin and phencyclidine. AB - Mice were exposed to diacetylmorphine (heroin) or phencyclidine (PCP) prenatally or neonatally. At a later age, they were tested for hippocampus-related behavioral deficits and concomitant alterations in the septohippocampal cholinergic innervations. Actually, this is an application of the previously established phenobarbital neuroteratogenicity model to heroin and PCP. Prenatal exposure was accomplished transplacentally by injecting the mother 10 mg/kg heroin or PCP on gestation days 9-18. Neonatal administrations were applied directly by injections of 10 mg/kg of either drug to the pups between neonatal days 2-21. At the age of 50 days, mice exposed to heroin and PCP prenatally exhibited a 107% and 159% increase in their muscarinic cholinergic receptors Bmax, respectively. Neonatal exposure to heroin or PCP caused an 83% and 76% increase in the receptors respectively. On the behavioral level, both prenatal and neonatal exposure to heroin or PCP reduced performance in the hippocampus related eight-arm maze and Morris mazes. Depending on the drug, the test and the period of drug administration, the reduction ranged between 10% and 75%. The results suggest that heroin and PCP induce alterations in the septohippocampal cholinergic innervations and in related behavioral performance. Further studies are necessary in order to connect the biochemical and behavioral events in causal relationships. PMID- 1424098 TI - Characterization of a novel set of membrane antigens associated with axonal growth. II. Expression in the chick central nervous system. AB - In the preceding paper (Dev. Brain Res., 69 (1992) 215-223), a polyclonal antiserum ('3070') and several monoclonal antibodies (MAbs 4 and 199) were used to define a novel set of laminin-binding membrane antigens in chick brain. These MAbs specifically inhibited attachment of NG108-15 cells to low, but not high amounts of laminin. Here, the immunocytochemical localization of MAb 4 and 3070 antigens was examined in frozen sections of E3-P21 chick brain, with particular reference to retina, optic tectum, cerebellum and spinal cord. Growing axons and migrating nascent neurons were stained transiently, while projection neurons were intensely labelled at all stages. Some interneurons and glial cells were stained faintly; others, apparently not at all. Finally, 3070 antiserum stained neuropil regions in mature brain. Cells in the CNS expressing high levels of MAb 4 antigens corresponded to those which, in rodents, are known to migrate in response to laminin or to synthesize forms of laminin themselves. These data, together with evidence presented elsewhere (J. Comp. Neurol., 313 (1991) 625-642) and in the next paper in this series (Dev. Brain Res., 69 (1992) 277-282), suggest that MAb 4 and 3070 antigens are important in neural development by mediating at least some of the responses of neural cells to laminin--for example, by acting as a laminin receptor guiding axonal outgrowth and neuronal migration, or by involvement in the transport and binding of laminin to the surface of neurons and reactive glial cells. PMID- 1424099 TI - An experimental model of generalized seizures for the measurement of local cerebral glucose utilization in the immature rat. I. Behavioral characterization and determination of lumped constant. AB - An experimental model of status epilepticus has been developed in the immature rat by administration of pentylenetetrazol (PTZ) using repetitive, timed intraperitoneal injections of subconvulsive doses. The pattern of behavioral signs has been well characterized in each age group, i.e. 10 (P10), 14 (P14), 17 (P17) and 21 postnatal days (P21). In this model, the dose of convulsant could be adjusted as a function of interindividual sensitivity and status epilepticus lated for quite a long duration to allow the measurement of local cerebral metabolic rates for glucose (LCMRglc) by means of the [14C]2-deoxyglucose method [J. Neurochem., 28 (1977) 897-916]. To estimate LCMRglc during status epilepticus, the lumped constant (LC) was re-calculated in controls and PTZ treated rats. The control LC was 0.54 at P10 and 0.50-0.51 at the three older ages studied (P14, P17 and P21). During status epilepticus, it increased to 0.64 in P10 rats and decreased to 0.42 and 0.40, respectively, in P17 and P21 animals. At P14, LC was not affected by seizures. The measurements of brain lactate levels showed a large 4.5-10-fold increase in PTZ-treated rats as compared to controls at all ages. The results of the present study show that the immature brain responds to sustained seizure activity in a specific way according to its postnatal age. Moreover, our results underscore the necessity of re-calculation of LC to the quantification of LCMRglc in such pathological states, particularly in immature animals. PMID- 1424100 TI - An experimental model of generalized seizures for the measurement of local cerebral glucose utilization in the immature rat. II. Mapping of brain metabolism using the quantitative [14C]2-deoxyglucose technique. AB - The quantitative autoradiographic [14C]2-deoxyglucose technique (2DG) was applied to measure the effects of pentylenetetrazol (PTZ)-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) in 10 (P10)-, 14 (P14)-, 17 (P17)- and 21 (P21)-day-old rats. To produce long-lasting SE (55 min), the animals received repetitive, timed intraperitoneal injections of subconvulsive doses of PTZ until SE was reached. At P10 and P14, SE induced a marked increase in LCMRglc which affected 66 of the 76 structures studied. Increases were especially high (200-400%) in limbic and motor cortices at P10 and in some brainstem areas at these 2 ages. At P17 and P21, average brain glucose utilization was similar in seizing and control rats, but in PTZ-treated rats reflected a redistribution in local metabolic rates with increases in brainstem, midbrain, hypothalamus and septum, decreases in cortex, hippocampus, some sensory areas and white matter and no change in many motor and limbic structures. In a few cerebral regions, such as hippocampus, dentate gyrus and mammillary body, LCMRglc did not increase at P10 and P14 and decreased at P17 and P21 in PTZ- vs. saline-treated rats. The results of the present study show that the immature brain responds to sustained seizure activity in a specific way according to its maturational state. Moreover, these data allow the mapping of the vulnerability of cerebral structures to seizures, according to their metabolic response to convulsions. PMID- 1424101 TI - Distribution and relative density of p75 nerve growth factor receptors in the rat spinal cord as a function of age and treatment with antibodies to nerve growth factor. AB - It has been postulated that nerve growth factor (NGF) binding to the low-affinity fast-dissociating NGF receptor (p75 NGFR) on Schwann cells and growing neurites is involved with the molecular feedback necessary for continued neurite extension during development and regeneration. Since central projections of somatosensory fibers sprout into the spinal cord after daily neonatal injections of antibodies to NGF (ANTI-NGF) for a one month period, it is of interest to determine if the distribution of p75 NGFR correlates with the occurrence of sprouting. Spinal cords from three groups of rats: untreated, preimmune sera treated and ANTI-NGF treated were examined on postnatal days (PD) 0, 14 and 30. The p75 NGFR distribution was determined using the monoclonal antibody 192 with standard immunohistochemical techniques and the optical density of the immunoreaction product was quantified using an Amersham image analysis system. The 192 immunoreaction product was localized to laminae I-IV, the dorsal columns, the dorsolateral funiculus, Lissauer's tract (LT) and the ventral horn on PD 0; to laminae I-III and medial IV and LT on PD 14; and laminae I-II and LT on PD 30. The untreated and preimmune sera treated groups show no difference in distribution. In the ANTI-NGF treated group, the 192 immunoreaction product was localized to laminae I-V and LT on PD 14 and to laminae I-III and medial IV and LT on PD 30. Similarly, the optical density of the ANTI-NGF treated group was significantly greater than same aged untreated and preimmune sera treated groups, but was not statistically different from these two groups examined 14 days earlier. Thus, ANTI-NGF treatment interferes with the postnatal downregulation of p75 NGFR in the dorsal horn and may provide for continued neurite growth. PMID- 1424102 TI - Effects of the subcutaneous administration of enkephalins on tail-flick response and righting reflex of developing rats. AB - The s.c. administration of [Met5]-enkephalin to 10-day-old rats pretreated with the mixture of 3 peptidase inhibitors, amastatin, captopril and phosphoramidon, produced the inhibition of tail-flick response and loss of righting reflex. When infant rats were pretreated with the mixture of any combination of two peptidase inhibitors, however, the change in both the response and the reflex were not produced at all by enkephalin injection, indicating that 3 kinds of enzymes, amastatin-sensitive aminopeptidase(s), captopril-sensitive peptidyl dipeptidase A and phosphoramidon-sensitive endopeptidase 24.11, played an important role in the inactivation of enkephalin after its systemic administration. Additionally, the fact that the two enkephalin-induced effects were more effectively antagonized by naloxone, a relatively selective mu-opioid antagonist, than by naltrindole, a specific delta-antagonist, or by nor-binaltorphimine, a specific kappa antagonist, showed that these two effects were produced by the interaction of enkephalin with mu receptors. Moreover the involvement of mu receptors in the production of these two effects was shown by the fact that the s.c. administration of [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a selective mu agonist, also produced these two effects which were more effectively antagonized by naloxone than by naltrindole or nor-binaltorphimine. Since the magnitude of the two effects induced by enkephalins in 15-day-old rats was significantly lower than that in 10-day-old rats, and the two enkephalin-induced effects were not produced at all in 20-day-old rats, a maturation-induced decrease in the permeability of the blood-brain barrier against opioid peptides was indicated. PMID- 1424103 TI - Characterization of novel set of membrane antigens associated with axonal growth. III: Expression in the regenerating goldfish optic nerve and tectum. AB - In the preceding two papers in this series, a polyclonal antiserum (3070) and several monoclonal antibodies (MAbs 4 and 199) were used to define a novel set of laminin-binding membrane antigens in chick brain. In chick brain, 3070 and MAb 4 antigens stained growing axons and migrating nascent neurons transiently; though projection neurons were intensely labelled at all stages, normal glial cells were stained faintly or not at all. To learn if these antigens are associated more generally with active states of nerve growth, the present paper examined the expression of 3070 and MAb 4 antigens during regeneration of the goldfish optic nerve. Only a few optic fibers or glial cells were stained by 3070 antiserum in the resting (uninjured) optic nerve, but 10 days following a unilateral nerve crush, when the growth response is maximal in these fish, distal regenerating neuritic sprouts and glial cell bodies and processes were profusely labelled. The intensity of labelling was diminished by 135 days post-crush, when most active growth was completed. Since 3070/MAb 4 antigens exhibit properties expected for functional laminin receptors, these findings suggest several possible roles that they could play to aid nerve regeneration. PMID- 1424105 TI - Clinical utility of zinc protoporphyrin. PMID- 1424104 TI - Fetal nicotine exposure ablates the ability of postnatal nicotine challenge to release norepinephrine from rat brain regions. AB - Exposure of the fetus to nicotine is known to affect the function of noradrenergic pathways in the central nervous system. In the current study, synaptic mechanisms underlying the functional defects were evaluated in the offspring of pregnant rats given nicotine infusions of 2 mg/kg/day throughout gestation, administered by osmotic minipumps. At 30 days postpartum, norepinephrine levels in brain regions of the offspring were significantly reduced. More importantly, acute challenge with either 0.1 mg/kg or 0.3 mg/kg of nicotine evoked significant norepinephrine release from brain regions of control animals, but failed to do so in the fetal nicotine cohort. These results suggest that prenatal exposure to nicotine produces a deficit in subsequent noradrenergic responsiveness, deficits which may participate in behavioral and neuroendocrine abnormalities. PMID- 1424106 TI - New biochemical marker for bone disease: is it a breakthrough? PMID- 1424107 TI - Parathyroid hormone-related protein: structure, function, and measurement. AB - Parathyroid hormone-related protein (PTHRP) is a 139- to 173-amino-acid protein with N-terminal homology to parathyroid hormone (PTH). Initially isolated from tumors from patients with humoral hypercalcemia of malignancy, PTHRP appears to be of far more widespread physiological importance. Its complex gene is expressed in a surprising diversity of tissues. The primary amino acid sequences of both the PTH-like and non-PTH-like regions of the protein are highly conserved across species. In addition to classical and nonclassical PTH-like activities of the N terminal region, other biological functions have been ascribed, including augmentation of calcium transport by midregion PTHRP and potent inhibition of bone resorption by a C-terminal peptide. There is emerging evidence that the protein undergoes extensive processing, including glycosylation and defined proteolytic cleavages. Several region-specific immunoassays are now capable of measuring circulating concentrations of PTHRP in patients with humoral hypercalcemia of malignancy. Molar concentrations of different regions may differ by more than an order of magnitude, reflecting diversity in processing and (or) metabolism. By analyzing the results of these assays, taking into account the specificities of known endoproteases, one can hypothesize about some of the endoproteolytic cleavages that occur in PTHRP metabolism. Clinically, selected PTHRP assays can be very helpful in diagnosing PTHRP-mediated hypercalcemia, but are not yet sufficiently sensitive to accurately measure normal concentrations of the protein. PMID- 1424108 TI - Washing erythrocytes to remove interferents in measurements of zinc protoporphyrin by front-face hematofluorometry. AB - Zinc protoporphyrin (ZPP) is determined by hematofluorometry of whole blood to detect iron deficiency in blood donors. In hospitalized patients, ZPP did not correlate with established markers of iron status. We performed 4500 ZPP measurements with the Aviv front-face hematofluorometer in samples from 475 patients and measured ferritin, transferrin saturation, hemoglobin, and erythrocyte indices. We found that the fluorometric determination is affected by substances dissolved in plasma but that this interference can be eliminated by using washed erythrocytes. In validation tests the within-day variation was < 3.5%; the day-to-day variation was < 6.8%. In 130 healthy persons without iron deficiency, ZPP was < or = 40 mumol/mol heme, which we consider a normal value. Mean ZPP in 46 iron-deficient patients was 256 (SD 105) mumol/mol heme (correlation with ferritin: -0.73; with hemoglobin: -0.85; P < 0.001). When washed erythrocytes are used, the hematofluorometric determination of ZPP is sensitive and specific for detecting iron deficiency in otherwise healthy individuals and hospitalized patients. PMID- 1424109 TI - Influence of obesity on plasma fructosamine concentration. AB - The influence of obesity on plasma fructosamine concentration was studied in 68 diabetic and 1335 nondiabetic subjects from a Chinese community. Obese nondiabetic men (body mass index > 25 kg/m2) had lower fructosamine concentrations than nonobese nondiabetic men (body mass index < or = 25 kg/m2); the pattern was similar for diabetic women. Stepwise multiple-regression analysis showed that, apart from known factors (total protein, albumin, and indices of glycemic control), fructosamine was also associated with body mass index and plasma fasting triglycerides. However, the contribution of these were small except in diabetic women. We conclude that the effect of obesity on fructosamine is small. PMID- 1424110 TI - Specific assay of serum lactate dehydrogenase isoenzyme 1 by proteolysis with alpha-chymotrypsin and protein denaturation. AB - We devised a method for assaying serum lactate dehydrogenase isoenzyme 1 (LD-1) activity specifically by preincubation with alpha-chymotrypsin and guanidine. Cleavage of phenylalanine bonds in the loop of A and B subunits of LD-3, LD-4, and LD-5 isoenzymes (residues 117-119) by incubation with alpha-chymotrypsin for a short time completely inactivated these isoenzymes and partially inactivated LD 2. Addition of guanidine (0.50 mol/L, pH 7.8) to the incubation mixture containing the chymotrypsin completed the inactivation of LD-2. As much as 4000 U/L of LD-2, LD-3, LD-4, and LD-5 were inactivated, whereas LD-1 was affected only slightly. Results by this method (y) correlated well with those by the Roche Isomune immunochemical LD-1 method (x): y = 0.98 x -0.11, r = 0.99 (n = 60). Within-run CVs were 0.5-2.5%. Several common interferents had no effect. In 500 healthy people, serum LD-1 ranged between 66 and 130 U/L, with a mean +/- SD of 88 +/- 15 U/L. PMID- 1424111 TI - Using 16O35Cl to correct for chloride interference improves accuracy of urine arsenic determinations by inductively coupled plasma mass spectrometry. AB - We have observed inaccurate urine arsenic values with the method of isobaric fractionation, which was designed to correct for the 40Ar35Cl interference with 75As quantitation by inductively coupled plasma mass spectrometry. Isobaric fractionation, which is based on ion intensities at m/z 77 and 82, consistently underestimates the 40Ar35Cl interference and overestimates urine arsenic. We present an improved method for identifying the argon-chloride interference. We observed that signal intensities for the species 16O35Cl and 40Ar35Cl are proportional (I75 = 0.0295 x I51 - 14.7, r2 = 0.998; where Ix is the normalized ion intensity at m/z X) in water and urine, over a broad range of chloride concentrations (0-800 mmol/L). The proportionality constant is remarkably stable within a run (mean and SD, 0.0295 +/- 0.0023, based on 10 replicates of five chloride calibrators, 0, 100, 200, 400, and 800 mmol/L). Increased sensitivity (50-fold) for detecting the 40Ar35Cl interference provides improved accuracy for urine arsenic quantitation as demonstrated by a split-sample comparison with graphite-furnace atomic absorption spectrophotometry. PMID- 1424112 TI - Development of monoclonal antibodies for an assay of cardiac troponin-I and preliminary results in suspected cases of myocardial infarction. AB - To improve the specificity of biochemical markers of myocardial infarction (MI), we have developed a double monoclonal "sandwich" enzyme immunoassay to measure cardiac troponin-I (cTnI) in serum. We produced eight IgG monoclonal antibodies against human cardiac troponin-I (cTnI) and tested them against human and animal (canine, bovine, and rabbit) troponins. Five antibodies were cardiac-specific; none of the antibodies were species-specific. Two of the five cTnI-specific monoclonal antibodies were utilized in an immunoassay. Standards were made by adding purified human cTnI to affinity-stripped cTnI-free human sera to cover the range 0-100 micrograms/L for cTnI. The dose-response curve was nonlinear but reproducible. Total assay imprecision (CV) varied between 11% and 21%. The upper limit of the reference range (nonparametric 95% interval) was established as 3.1 micrograms/L by measuring cTnI concentration in sera of 159 hospitalized patients without evidence of cardiac disease. Purified human skeletal TnI up to 10,000 micrograms/L did not affect the assay (calculated cross-reactivity < 0.1%). Diagnostic sensitivities of creatine kinase MB isoenzyme (CK-MB) and cTnI were evaluated retrospectively in 49 consecutive patients with proven MI. In the 30 patients for whom sufficient information was available to establish an accurate time course, CK-MB was more sensitive during the first 4 h after the onset of chest pain, but thereafter the sensitivities were similar up to 48 h. However, cTnI is more cardiac-specific than is CK-MB and remains increased longer than does CK-MB. PMID- 1424113 TI - Automated analysis for free and short-chain acylcarnitine in plasma with a centrifugal analyzer. AB - We describe a fully automated, spectrophotometric assay of free and total carnitine in plasma ultrafiltrates. The method, suitable for routine application in most hospital laboratories, incorporates the hydrolysis of acylcarnitines to free carnitine within the program of a Cobas Fara II centrifugal analyzer. The hydrolysis is monitored and calibrated with standard solutions containing octanoylcarnitine. Results correlated well with those from a reference isotope dilution mass spectrometric assay. The ability to analyze a batch of samples for both free and total carnitine within 90 min enables analysis of > or = 100 samples per day. Used in conjunction with acylcarnitine species identification by mass spectrometry, the Cobas assay facilitates the diagnosis of carnitine deficiency syndromes and specific metabolic disorders. PMID- 1424114 TI - Simple method for correcting total protein in plasma for actual fibrinogen content. AB - Using plasma instead of serum for routine chemistry analyses has many advantages. To overcome the disadvantage of inclusively measuring fibrinogen in the plasma total protein assay without changing the clinical significance of the total protein assay, we investigated the possibility of subtracting the actual amount of fibrinogen from the plasma total protein. The correlation between serum and plasma total protein was excellent (plasma total protein = 0.989 x serum total protein + 6.7 g/L; r = 0.969; n = 131; mean difference = 5.55 g/L; P < 0.001). When the plasma total protein was corrected for the actual amount of fibrinogen, the correlation with serum total protein was equally good but the intercept was practically eliminated (corrected plasma total protein = 1.009 x serum total protein + 0.25 g/L; r = 0.985; n = 131; mean difference = 0.78 g/L; P = 0.47). The mean concentration of fibrinogen was 2.5 g/L (range: 1.38-3.62 g/L; n = 404) for blood donors, 3.6 g/L (n = 2707) for patients from the outpatient department, 4.6 g/L (n = 2023) for patients admitted to the hospital, and 6.6 g/L (n = 219) for patients whose concentration of C-reactive protein was > 50 mg/L. We conclude that the plasma total protein result should be corrected for the actual amount of fibrinogen. PMID- 1424115 TI - Ratio of creatine kinase 2 mass concentration to total creatine kinase activity not altered by heavy physical exercise. AB - Serum creatine kinase isoenzyme 2 concentrations (CK 2 mass) were measured in marathon runners during training and 1 and 2 days after a race and compared with values from 36 acute myocardial infarction (AMI) patients whose total CK and (or) CK 2 activities were similar to those of runners in the basal state. During training, runners had CK and CK 2 activities 53% and 43% above reference values, respectively, and 36% had CK 2 activity > 5% of total CK. Nine runners (26%) showed CK 2 mass values > 6 micrograms/L but < or = 10 micrograms/L; 35 of the AMI subjects, despite having CK activities similar to those of runners, had values > 10 micrograms/L. The ratio of CK 2 mass to total CK activity was significantly (P < 0.0002) different between sexes for runners. At 1 and 2 days after racing, 100% of CK and CK 2 activities and 71% and 57% of the percentages of CK 2 activity, respectively, were abnormally high; 57% and 43% of CK 2 mass values were > 10 micrograms/L, being comparable with those observed for the AMI group. Basal CK 2 mass values of the runners appeared only slightly higher than that for sedentary subjects, but after exercise half the subjects presented increased values similar to those observed for AMI subjects. The ratio of CK 2 mass to total CK activity appeared unaltered by exercise in all but one of the samples assayed, indicating its utility in evaluating CK 2 mass increases originating in skeletal muscle. PMID- 1424116 TI - Cross-reactivity of anti-digoxin antibodies with digitoxin depends on tracer structure. AB - The most common methods for measuring digoxin concentrations in serum are immunoassays. The prerequisite for exact determination of the digoxin value is an antibody that specifically binds digoxin. Because digitoxin differs from digoxin only in the C-12 hydroxy group, it is difficult to obtain anti-digoxin antibodies that do not cross-react with this compound. During the development of a fluorescence polarization immunoassay (FPIA) for digoxin, we investigated digoxin tracers with different structures. We found that in FPIA the digitoxin cross reactivity of an antibody could be reduced by varying the structure of the tracer molecule. PMID- 1424117 TI - Sandwich immunoassay for intact human osteocalcin. AB - To overcome the problems of limited-region specificity associated with conventional radioimmunoassay (RIA), we developed a sandwich enzyme immunoassay (EIA) for intact human osteocalcin (hOC). For this EIA we used antibodies to the N- and C-terminal regions of hOC that were raised against an N-terminal 20 residue peptide and a C-terminal 7-residue peptide, both synthetic. Immunoassay profiles of tryptic digests of hOC and serum from patients with renal failure, fractionated by reversed-phase HPLC, facilitated direct demonstration of the region specificity of this method. A preliminary study of serum osteocalcin concentrations in patients with renal failure further confirmed this specificity, showing lower positive rates obtained by this method than by conventional RIA. The cross-reactivity data of hOC with bovine and rat osteocalcins by the sandwich method indicated its species specificity. These studies demonstrate the superior specificity of this sandwich EIA compared with conventional RIA and thus confirm its potential diagnostic superiority. PMID- 1424118 TI - Apolipoprotein(a) is present in urine and its excretion is decreased in patients with renal failure. AB - To investigate the relation between renal function and concentrations of lipoprotein(a) [Lp(a)] in serum, we measured Lp(a) in samples of serum and urine from patients with diabetes mellitus and in samples sent to a laboratory center for measurements of creatinine clearance. Serum Lp(a) concentrations were significantly increased in subjects with obvious renal dysfunction (serum creatinine > or = 176.8 mumol/L) compared with normal control subjects. Urinary Lp(a) excretion was decreased in subjects with obvious renal dysfunction compared with subjects without obvious renal dysfunction (serum creatinine < or = 88.4 mumol/L) and was negatively and positively correlated with serum creatinine and creatinine clearance, respectively. More than 80% of urinary Lp(a) was recovered in the d > 1.21 kg/L fraction. At least six bands for apolipoprotein(a) [apo(a)] fragments, which were smaller than native apo(a) in serum, were observed in urine by immunoblotting, and some of these were also detected in serum. Degraded apo(a) fragments are probably present in urine, and their excretion decreases in parallel with decreases in the glomerular filtration rate. PMID- 1424120 TI - Analytical goal-setting for monitoring patients when two analytical methods are used. AB - Serial results from an individual are often obtained using more than one method. Results should be transferable over time and locale. Every method has inherent analytical error, and goals are required to delineate the maximum allowable random (imprecision) and systematic (inaccuracy, bias) errors to facilitate optimal patient care. Based on Harris's proposal [Am J Clin Pathol 1979;72:374 82] that desirable imprecision should be less than or equal to one-half the within-subject biological variation, if the methods have negligible imprecision, then the maximum allowable bias between two methods used for monitoring is one third of the within-subject biological variation. A more general model has been developed that relates the analytical imprecisions of two methods, and the bias between them, to biological variation. Applying the general formula derived in specific clinical monitoring situations in which a known change in serial results (occurring at a stated probability) stimulates clinical action allows goals for the imprecisions of the two methods and allows the difference in bias between them to be determined quantitatively. PMID- 1424119 TI - Rapid nonradioactive tracer method for detecting carriers of the major Ashkenazi Jewish Tay-Sachs disease mutations. AB - Tay-Sachs disease (TSD, GM2 gangliosidosis, Type I) is an autosomal recessive lysosomal storage disease caused by deficiency of beta-hexosaminidase A (Hex A) resulting from mutations in the gene (HEXA) encoding the alpha-subunit of the enzyme. Three mutations, in exons 7 and 11 and at the exon 12-intron 12 junction, account for > 90% of alleles identified in obligate Ashkenazi Jewish carriers. Mutation analysis requires amplification of available DNA by separate polymerase chain reactions (PCRs) and either restriction digestion and gel electrophoresis or 32P-labeled allele-specific oligonucleotide (ASO) probes. We developed a simple, nonradioisotopic method for rapidly identifying TSD carriers by a triplex PCR reaction followed by dot-blot analysis, using three wild-type and three mutant ASOs end-labeled with digoxigenin-dUTP (dig-ASO). Hybridization was demonstrated immunologically by reaction with an anti-digoxigenin-alkaline phosphatase conjugate followed by colorimetric demonstration of phosphatase activity. The results of analyses by the dig-ASO method of 65 carriers identified by serum enzyme activity and of 6 high-risk fetuses in prenatal testing were the same as those obtained by more conventional restriction analysis. Dig-ASO testing correctly reclassified 10 individuals who had tested inconclusively on analysis for leukocyte beta-hexosaminidase A activity; 3 were identified as carriers and 7 as noncarriers. The simplicity of the assay and the avoidance of the radioisotopes make this a potentially useful method for TSD carrier detection by mutation analysis in Ashkenazi Jews from populations in whom the identity and frequencies of the common TSD mutations are known. PMID- 1424121 TI - Plasma lipoprotein(a) values and severity of coronary artery disease in a large population of patients undergoing coronary angiography. AB - To determine possible associations between lipoprotein(a) [Lp(a)] and the severity of coronary artery lesions, we measured lipid, apolipoprotein, and Lp(a) in a large population of Belgian patients (n = 1054) undergoing coronary angiography. In both women and men, univariate analysis demonstrated significant differences in the Lp(a) concentrations according to the severity of the coronary stenosis. However, after adjustment for possible confounding factors, many of these differences were attenuated, indicating that other variables that differentiate patients from control subjects also influence Lp(a) distribution. Differences in lipid, apolipoprotein, and Lp(a) concentrations between male and female patients are discussed. PMID- 1424122 TI - Immunoluminometric assay of chromogranin A in serum with commercially available reagents. AB - Chromogranin A (Cg A) is a useful marker of neuroendocrine neoplasia in humans. Here we describe an immunoluminometric assay (ILMA) for measuring Cg A in serum, with use of a new tube as a solid phase. The new tube has a large surface area and is coated with a polyclonal antibody. Optimized coating conditions provide a high IgG adsorption to the polystyrene wall. Serum is added to the coated tube and incubated for 2 h or overnight. After washing the tubes, acridinium ester labeled monoclonal antibody against Cg A is added and incubation is continued for 2 h. The tubes are washed again and the bound luminescence is measured. The assay is very sensitive (detection limit 1 microgram/L, if 25 microL of serum is used), is specific for human Cg A, and offers a wide dynamic range (1-1000 micrograms/L). The range in healthy humans is 10-53 micrograms/L (median 30 micrograms/L). The correlation of serum Cg A to creatinine and parathyroid hormone is described. We also report the influence of intravenous calcium injection on Cg A concentrations in serum. PMID- 1424123 TI - Pre-beta high-density lipoprotein determined by immunoblotting with chemiluminescent detection. AB - We describe a novel assay of pre-beta high-density lipoprotein (HDL), a unique apolipoprotein A-I (apo A-I)-containing lipoprotein particle. The pre-beta and alpha lipoproteins are separated by electrophoresis in agarose and transferred onto a membrane by capillary blotting. The membrane blot is sequentially incubated with sheep anti-human apo A-I antiserum and then with a conjugate of rabbit anti-sheep immunoglobulin and horseradish peroxidase. Chemiluminescence formed by the peroxidase-catalyzed oxidation of luminol in the presence of an enhancer is captured on photographic film, and the pre-beta HDL band is quantified by transmission densitometry. The assay is calibrated with standards prepared from a reference serum diluted in 9 mol/L urea. Within-batch precision (CV) at pre-beta HDL concentrations of 22.1 and 44.3 mg/L was 7% and 4.9% respectively. Pre-beta HDL contained 1.6% (0.65-2.6%, mean and range) of total serum apo A-I in 30 normolipidemic subjects. PMID- 1424124 TI - Pitfalls in the measurement of plasma osmolality pertinent to research in vasopressin and water metabolism. AB - The reliability of measurements of plasma osmolality is known to be biased by technical artifacts, such as the anticoagulant and the osmometric technique used; the resulting measurement errors therefore may cause errors in interpretation of data. In assessing the potential biasing influence of procedural variables, we found that the temperature at which fresh plasma samples were stored, the duration of storage, and the freezing and thawing of samples appeared to significantly (P < 0.01) affect osmolality values around the narrow physiological range. These factors should be considered in the interpretation of studies on the osmoregulation of vasopressin secretion. In particular, the results suggest that data obtained for any but fresh samples, whether frozen-thawed samples or samples stored at room temperature, are unreliable. PMID- 1424125 TI - Abbott IMx and serono MAIAclone assays compared for lutropin determinations in urine. AB - The urinary lutropin (luteinizing hormone; LH) profiles of 20 patients were determined in 10 consecutive urine samples (n = 200) with a manual technique (MAIAclone, Serono; y) and a fully automated (Abbott IMx; x) technique. For 132 single determinations within the range of detection, the regression line was y = 1.39 x - 0.07 (r = 0.85). Retrospective analysis of the LH profiles obtained by the IMx yielded the classification "not pregnant" (negative) in 14 cases, of which 13 were correctly classified; 6 profiles were classified as "pregnant" (positive), which correlated with the clinical findings in 4 cases. Nine of the LH profiles analyzed with the MAIAclone method were classified as negative, which was correct in seven cases. Retrospective analysis of 11 LH profiles established with the MAIAclone assay gave positive results, which agreed with the clinical outcome in three cases. The diagnostic sensitivity of the IMx and MAIAclone methods was 87% and 47%, respectively; diagnostic specificity was 80% and 60%, respectively. In smaller series (< or = 40 samples), the IMx method has considerable advantages over the MAIAclone method in cost and convenience, because standard curves can be stored and assays can be performed as single determinations. PMID- 1424126 TI - Investigation of N-methyl-D-glucamine buffer for assay of alkaline phosphatase in serum. AB - We evaluated N-methyl-D-glucamine (MEG) as a buffer for assay of alkaline phosphatase (ALP; EC 3.1.3.1) and compared the MEG-based assay with the current International Federation of Clinical Chemistry Reference Method for ALP (IFCC/RM/ALP), in which 2-amino-2-methyl-1-propanol (AMP) is the pH buffer. The ALP assay in MEG at 30 and 37 degrees C shows excellent correlation with the IFCC/RM/ALP at 30 degrees C, but yields proportionately higher ALP activities (8.2% at 30 degrees C and 57% at 37 degrees C). ALP is unstable in both MEG and AMP at 37 degrees C. Serum incubated in MEG undergoes a pH-dependent biphasic loss of ALP activity: an initial rapid 5% loss after 1 min of incubation and a 10% loss per hour thereafter. A similar pattern was seen for incubation with AMP. The use of a serum-initiated reaction (no preincubation of enzyme with buffer) eliminated the early loss in activity. The addition of the metal ion buffer N hydroxyethylethylenediaminetriacetic acid, along with low concentrations of Zn and Mg, as used in the IFCC/RM/ALP, reduced the slow loss in activity over time, as did decreasing the reaction temperature to 30 degrees C, but had no effect on the early rapid decay in activity seen in the first minute. Moderate transphosphorylation (45%) and nonenzymatic hydrolysis (3.3 U/L) were observed with MEG under the conditions of the assay (37 degrees C). A comparison of different lots of MEG from two manufacturers showed no significant difference in ALP activities. PMID- 1424127 TI - Decreases in albumin/creatinine and N-acetylglucosaminidase/creatinine ratios in urine samples stored at -20 degrees C. AB - The effects of storage for 6 months or 2 years at -20 degrees C were studied in urine samples from Type II diabetic patients by assaying albumin by immunoturbidity, N-acetylglucosaminidase (EC 3.2.1.30) by methoxynitrovinylphenol release, and creatinine by the Jaffe method. There were significant decreases (P < 0.001) in albumin/creatinine ratios from 1.14 (0.63-2.98) to 0.83 (0.32-2.12) g/mol (median + interquartile ranges) after 6 months (n = 97), and from 1.64 (0.74-5.72) to 1.00 (0.37-4.54) g/mol after 2 years (n = 89). The percentage of samples with results below the detection limit of the albumin assay (2 mg/L) increased from 5% to 21% after 6 months and from 0% to 34% after 2 years. N Acetylglucosaminidase/creatinine ratios decreased (P < 0.001) from 520 (358-832) to 380 (263-695) U/mol after 6 months and from 520 (330-865) to 258 (82-462) U/mol after 2 years. The effect of storage was greater in samples with concentrations in the normal range (< 2.5 g/mol for albumin/creatinine, < 500 U/mol for N-acetylglucosaminidase/creatinine). Samples with albumin concentrations more than twice the normal range were still detected as abnormal after storage at -20 degrees C; e.g., 18% were > 5 g/mol (albumin/creatinine) initially, with 17% > 5 g/mol after 6 months of storage. We therefore recommend storage of urine samples at 4 degrees C for no longer than 7 days before assay. PMID- 1424128 TI - Measurement of cyclosporine by liquid chromatography and three immunoassays in blood from liver, cardiac, and renal transplant recipients. AB - In an effort to replace HPLC for whole-blood determination of cyclosporine (CsA), we compared HPLC with radioimmunoassay (RIA; INCSTAR, Cyclo-Trac SP assay), fluorescence polarization immunoassay (FPIA; Abbott TDx), and in-house modified enzyme-multiplied immunoassay technique (EMIT; Syva Co.). For blood samples from 200 various transplant recipients, RIA = 1.262 (HPLC) - 8.16, r = 0.983; FPIA = 1.200 (HPLC) + 19.90, r = 0.981; and EMIT = 1.038 (HPLC) + 11.28, r = 0.985. For segregation by transplant type, RIA, FPIA, and EMIT demonstrated positive biases of 27%, 12%, and 3%, respectively, for liver transplant recipients (n = 50) when compared with HPLC. Heart transplant recipients (n = 50) gave positive bias values of 23%, 14%, and 4% for RIA, FPIA, and EMIT, respectively. Adult renal transplant recipients (n = 50) demonstrated positive bias values of 30%, 31%, and 0% for RIA, FPIA, and EMIT, respectively. For pediatric renal transplant recipients (n = 50), positive biases of 40%, 31%, and 9% were obtained for RIA, FPIA, and EMIT, respectively. We conclude that the modified EMIT represents the best replacement for HPLC. PMID- 1424129 TI - Bone-resorption markers galactosyl hydroxylysine, pyridinium crosslinks, and hydroxyproline compared. AB - We compared the clinical performances of four bone-resorption (BR) assays (hydroxyproline, HYP; galactosyl hydroxylysine, GHYL; deoxypyridinoline, DPD; and pyridinoline, PYD) in subjects with different BR rates: normal (adult men and premenopausal women), mildly increased (postmenopausal osteoporotic women), high (Paget disease patients), and very high (children). The discrimination power (Z score) and the accuracy (estimated by receiver-operating characteristic analysis) for GHYL, DPD, and PYD were compared with those for HYP. Discrimination power and accuracy were similar for high- and very-high-BR groups for all four assays. However in the mildly increased-BR group, DPD, GHYL, and PYD showed a higher discrimination power and accuracy than did HYP. The clinical performances of HYP, DPD, GHYL, and PYD are comparable for large changes in BR. For modest changes, DPD, GHYL, and PYD are more accurate and have a higher discrimination power than does HYP. PMID- 1424130 TI - Determination of creatinine in serum by capillary zone electrophoresis. PMID- 1424131 TI - Rapid quantification of quinidine in porcine serum by microbore HPLC with fluorescence detection. PMID- 1424132 TI - A new case of IgE myeloma. AB - We report a case of IgE myeloma in a 78-year-old woman who presented with bone pain in the shoulder and hip and progressive weakness. Except for hypercalcemia, routine chemistry values were within normal limits. Hemoglobin was decreased and the leukocyte count slightly increased. Plasma cells were not observed in the peripheral blood. Serum protein electrophoresis showed a monoclonal protein in the beta-globulin fraction. Immunofixation confirmed the presence of an IgE kappa monoclonal protein. A bone marrow biopsy revealed an interstitial and nodular infiltration of abnormal plasma cells comprising 60% of nucleated cells present. Skeletal roentgenograms and bone scans of this patient showed osteolytic lesions and osteopenia of the thoracic and lumbar spine and osteolytic destruction of the right half of the sacrum. Flow-cytometric analysis of mononuclear cells isolated from peripheral blood showed that 15% of the lymphocytes bound IgE. Using cell surface markers, we identified 45% of the IgE-positive cells as natural killer cells. Similar results have been found in other diseases marked by increased IgE. The clinical, radiological, and laboratory findings for this patient are compared with previously reported cases of IgE and other types of myeloma. PMID- 1424133 TI - External quality control for radioimmunoassay of urinary albumin in diabetic subjects: a one-year experience. PMID- 1424134 TI - Nongaussian distribution of second-trimester results for serum free estriol. PMID- 1424135 TI - Performance of a modified HPLC method to determine total hydroxyprolinuria in 2-h urine samples. PMID- 1424136 TI - Cellular phosphate shifts during oral glucose loading. PMID- 1424137 TI - Plasma vitamin E, non-high-density lipoprotein cholesterol, and apolipoprotein B in diabetic patients. PMID- 1424138 TI - Effect of pyridoxal 5-phosphate on the stability of alanine aminotransferase. PMID- 1424139 TI - Urinary glycosaminoglycans in active Graves ophthalmopathy. PMID- 1424140 TI - Estimating the prevalence of xanthinuria by laboratory screening. PMID- 1424141 TI - Heterogeneity of lipoprotein A-I. PMID- 1424142 TI - Validity of intact plasma parathyrin measurements in chronic renal failure as determined by two-site immunoradiometric assays with N- or C-terminal capture antibodies. PMID- 1424143 TI - Interference in the Allegro immunoassay system when blood is collected in silicone-coated tubes. PMID- 1424144 TI - Chromogranin A concentrations in plasma of physically active men after acute exercise. PMID- 1424145 TI - REMEDi drug profiling system readily distinguishes between cyclobenzaprine and amitriptyline in emergency toxicology urine specimens. PMID- 1424146 TI - No time-dependent change in cytochrome P-450 2D6 phenotyping results during HPLC analysis. PMID- 1424147 TI - Impact of revised NIDA guidelines for methamphetamine testing in urine. PMID- 1424148 TI - Inaccuracy of dispensing sample and reagent volume by the Cobas-Bio analyzer. PMID- 1424149 TI - Abnormal lactate dehydrogenase isoenzyme pattern in serum of a patient with a testicular tumor. PMID- 1424150 TI - One-step, labeled-antibody assay for measuring free thyroxine. 1. Assay development and validation. PMID- 1424151 TI - Finally! Automated microanalysis of ammonia in arterial blood. PMID- 1424152 TI - A hyaluronan-loading test applied to patients with liver and joint diseases. AB - The serum hyaluronan disappearance data, after an intravenous bolus injection of hyaluronan, were evaluated in terms of model-based parameters. The loading test was performed in 10 healthy persons (basal serum hyaluronan concentration, C0, 24.9 +/- 8.9 micrograms/l [mean +/- S.D.]), 6 patients with joint disease (62.3 +/- 41.1 micrograms/l) and 19 patients with liver disease (206 +/- 214 micrograms/l). The highest maximum Michaelis-Menten elimination rate (Vmax = 287 +/- 86 micrograms/min) was found in patients with joint disease, significantly higher than in healthy persons (Vmax = 179 +/- 16, P = 0.0015) and in patients with liver disease (Vmax = 149 +/- 59, P = 0.0002). C0 and Vmax were evaluated as discriminants for assessment of residual liver function. In patients with liver disease C0 correlated with liver function score (r = 0.875, P < 0.0001) and serum albumin concentration (r = -0.813, P < 0.0001). The Vmax parameter did not correlate with conventional liver function tests or with the liver score but a significantly negative correlation of Vmax with C0 was found in patients with liver disease. A combination of the C0 level and the Vmax parameter was found to discriminate between healthy persons, patients with joint disease and patients with liver disease and should be of benefit in separating patients, with or without elevated serum hyaluronan levels, into groups having increased influx or reduced elimination, respectively, of circulating hyaluronan. PMID- 1424154 TI - Pregnancy-associated alpha 2-glycoprotein in children with acute lymphocytic leukemia, Hodgkin's disease and non-Hodgkin's lymphomas. PMID- 1424153 TI - Cellulose acetate electrophoretic determination of bone alkaline phosphatase activity in healthy subjects and diabetic patients with and without osteopenia. AB - We adapted the electrophoretic method of bone alkaline phosphatase (ALP) determination using neuraminidase from Vibrio cholerae to separate bone and liver ALP on cellulose acetate membrane. Treatment of separator plus serum (1:8, neuraminidase 111 U/l in final) for 10 min at room temperature (25 +/- 1 degree C) and subsequent electrophoresis made it possible to quantify bone ALP activity simply and rapidly. The precision of the data was at the level of CV of 1.6% (within-day) and 4.7% (day-to-day), with recovery rates of 97-103%. The normal range of bone ALP activity depended on age and sex. Seventy-eight diabetes mellitus (DM) patients, excluding those with renal failure, were divided into two groups of those with and without osteopenia with matching of age (+/- 3 years) and sex. Bone ALP (P < 0.001) and total ALP (P < 0.05) activities and urine calcium/creatinine ratio (P < 0.05) were significantly higher in DM with osteopenia than in DM without osteopenia. Therefore, bone formation and absorption may be accelerated in DM with osteopenia in comparison with DM without osteopenia. PMID- 1424155 TI - PAF acetylhydrolase activities in human systemic lupus erythematosus and lupus prone mice. PMID- 1424156 TI - CA 19-9 in non-neoplastic liver diseases. A clinical and laboratory study. AB - CA 19-9 is a tumor marker with frequent false-positive results in pancreatic and hepatobiliary diseases. This study was carried out to evaluate the behaviour of CA 19-9 in 159 patients with benign diffuse hepatic disease, 85 cirrhotics and 74 non-cirrhotics, who underwent a thorough clinical and laboratory evaluation. CA 19-9 was correlated with numerous clinical and biochemical features of liver diseases: bilirubin and alkaline phosphatase activity were the most reliable predictors of the CA 19-9 concentrations. There were abnormal concentrations of CA 19-9 in 34.6% of the 159 patients and in 47.1% of the 85 cirrhotics. Because of the large number of abnormal values and the high concentrations attained in some of them, the cut-off used in patients with diffuse hepatic disease needs to be set at more than twice the basal level, thus allows only 10% of false positives. Even higher values are required for cirrhotic or icteric patients. The results indicate that cholestasis plays an important role in causing the raised CA 19-9 in these patients, although there were also abnormal concentrations in normobilirubinemic patients. PMID- 1424157 TI - A rapid method for blood ammonia determination using the new blood ammonia checker (BAC) II. PMID- 1424158 TI - Arginase, a new marker of mammary carcinoma. AB - Activities of arginase, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were determined in sera obtained in a group of healthy women, women with verified carcinoma of the breast, benign mastopathy, a group of patients with carcinoma of various organs and a group of patients with acute viral hepatitis. Preoperative values of serum arginase activity in patients with breast carcinoma were up to 4-fold those found in healthy women. Sensitivity of the test was 86%. After the surgery, the activity decreased abruptly during the first week and normalised within 15-30 days. In benign diseases of the breast, the activity of arginase was normal. Serum arginase activity is raised in both benign and malignant liver diseases, however, the quotients alanine aminotransferase/arginase, aspartate aminotransferase/arginase and alkaline phosphatase/arginase differ significantly. Thus, use of alanine aminotransferase/arginase quotient implies a high degree of confidence in differentiating between increased arginase activity in mammary carcinoma (alanine aminotransferase/arginase = 0.572 +/- 0.278) and high arginase activity in hepatitis (alanine aminotransferase/arginase = 12.226 +/- 1.822). PMID- 1424159 TI - Identification of urinary metabolites of (+/-)-2-(p-isobutylphenyl)propionic acid (Ibuprofen) by routine organic acid screening. AB - Ibuprofen [(+/-)-2-(p-isobutylphenyl)propionic acid] has recently been introduced as a pediatric anti-inflammatory agent. To determine how this agent interferes with urine organic acid analysis, an important pediatric investigation, we have analyzed urine from two subjects pre- and post-Ibuprofen dosage and two subjects on chronic Ibuprofen therapy. A distinctive pattern of drug interference on the organic acid profile was detected. There were three major components, corresponding to unmetabolized Ibuprofen and to the oxidation products hydroxy Ibuprofen and carboxy Ibuprofen. Therefore, the major mechanism of Ibuprofen metabolism appears to be microsomal, although mitochondrial and peroxisomal routes cannot be excluded. Laboratories carrying out routine organic acid analysis should be aware of the nature and magnitude of the organic aciduria caused by Ibuprofen. PMID- 1424160 TI - Intestinal type alkaline phosphatase hyperphosphatasemia associated with liver cirrhosis. AB - Hyperphosphatasemia due to increased intestinal type serum alkaline phosphatase was noted in a 48-year-old male who had asymptomatic liver cirrhosis. The alkaline phosphatase activity in the serum was 828 U/l (our reference range in adults: 57-194 U/l), 94% of which was of the intestinal type as measured by an immunoprecipitation method. The intestinal component of alkaline phosphatase was separated into two major and some minor components using electrophoresis and isoelectrofocusing. One of the major components had similar mobility to that of a standard intestinal enzyme purified from adult intestine. The components were heat-labile and neuraminidase-resistant. Serial lectin affinity chromatography, however, indicated that sugar chain compositions of the alkaline phosphatase were different from those of the standard tissue intestinal enzyme. These results and further enzymological studies suggest that the patient's serum alkaline phosphatase basically consisted of several intestine-like isoforms. PMID- 1424161 TI - Purification of electron transfer flavoprotein from pig liver mitochondria and its application to the diagnosis of deficiencies of acyl-CoA dehydrogenases in human fibroblasts. AB - Medium chain acyl-CoA dehydrogenase (MCAD) and long chain acyl-CoA dehydrogenase (LCAD) deficiency are defects of mitochondrial beta-oxidation. The method of choice to measure specifically acyl-CoA dehydrogenase activity in human tissues uses purified electron transfer flavoprotein (ETF). We describe a simple and optimized method of purification allowing isolation of ETF with a degree of purity never reported so far. An assay for acyl-CoA dehydrogenase activity in cultured skin fibroblasts was developed using microquantities of electron transfer flavoprotein and substrate. MCAD deficiency was demonstrated in fibroblasts from nine patients and LCAD deficiency in fibroblasts from two patients. PMID- 1424162 TI - Autoimmune thyroiditis: predisposition and pathogenesis. PMID- 1424163 TI - Primary hyperparathyroidism: aggressive or conservative treatment? PMID- 1424164 TI - Computed tomography and magnetic resonance imaging of pituitary microadenomas. PMID- 1424165 TI - The evaluation of patients with a suspected pituitary microadenoma: computer tomography compared to magnetic resonance imaging. AB - OBJECTIVES: To perform a prospective study to compare the ability of magnetic resonance imaging (MRI) and computer assisted tomography (CT) to predict the position of a tumour within the pituitary fossa and to assess the clarity of the image generated by the two modalities in patients with suspected pituitary microadenomas. DESIGN: Nineteen patients were investigated with CT and MRI scans and underwent trans-sphenoidal exploration of the pituitary fossa. Both scans were assessed blind and independently by three neuroradiologists, A, B, and C; A and B examined the CT scans and B and C the MRI scans. The predicted site was then compared to the size and position of the tumour at surgery. PATIENTS: Twenty five patients were recruited and had both CT and MRI scans, 19 subsequently underwent trans-sphenoidal exploration of the pituitary fossa and formed the study population. RESULTS: The joint opinions of A and B of the CT scans were correct in 10/19, and those of B and C of the MRI scans were correct in 17/19 cases, P = 0.008. Observer agreement was used to assess the clarity of the image. A and B agreed about the site of the tumour on the CT scan in 14 of 19 cases (Kappa statistic 0.556); B and C agreed on the MRI scans in 19/19 cases (Kappa statistic 1), P = 0.025. After the exclusion of five cases found to be macroadenomas at surgery, the joint opinions of A and B of the CT scans were correct in 8/14, and those of B and C of the MRI scans were correct in 12/14 cases, P = 0.133. A and B agreed about the site of the tumour on the CT scan in 12/14 cases (Kappa statistic 0.653), B and C agreed on the MRI scans in 14/14 cases (Kappa statistic 1, no significant difference). CONCLUSIONS: In the assessment of suspected pituitary microadenomas MRI is the imaging technique of choice in view both of its greater diagnostic accuracy and the avoidance of radiation exposure. PMID- 1424166 TI - Age related changes in follicle stimulating hormone, luteinizing hormone, oestradiol and immunoreactive inhibin in women of reproductive age. AB - OBJECTIVE: In women over the age of 45 years with continuing regular menstrual cycles, follicular phase FSH levels rise without an accompanying change in LH. We determined the effect of increasing age in women with regular cycles on the serum levels of FSH, LH, immunoreactive inhibin, progesterone and oestradiol. DESIGN: Single blood samples were taken during the early follicular phase (days 4-7) and again in the midluteal phase (3-12 days before the next menses) of the menstrual cycle. PATIENTS: Regularly cycling women aged 21-49 years participated in the study (and were grouped into four groups: 20-29, 30-39, 40-44 and 45-49 years in the follicular phase and three groups: 20-29, 30-39 and 40-49 years in the luteal phase. MEASUREMENTS: Serum levels of FSH, LH, oestradiol, progesterone and immunoreactive inhibin were measured from the blood samples obtained. RESULTS: Follicular phase Mean follicular phase levels of immunoreactive inhibin were significantly lower in the 45-49 year age group (P less than 0.05) than in the younger age groups (128 U/l in the 45-49 year age group vs 239, 235 and 207 U/l in the 20-29, 30-39, 40-44 year age groups respectively), while mean FSH levels were significantly higher in the 45-49 year age group (P less than 0.05, 13.0 IU/l in the 45-49, 4.9, 5.5 and 5.2 IU/l in the 20-29, 30-39 and 40-44 year age groups respectively). Mean oestradiol levels in the 45-49 year age group were significantly lower only when compared to age group 30-39 years (P less than 0.05, 130 vs 210 pmol/l). There was no significant difference in oestradiol levels between the 45-49 year age group and the 20-29 and 40-44 year age groups. LH levels did not differ significantly across age groups. There was also a significant negative correlation between serum immunoreactive inhibin and FSH (r = -0.45, P less than 0.05) and between oestradiol and FSH (r = -0.35, P less than 0.05). There was a significant negative relationship between immunoreactive inhibin and age (r = -0.46, P less than 0.05). For every 10-year increase in age, average immunoreactive inhibin decreased by an estimated 49.3 U/l. As age increased, average FSH levels exhibited a two-phase linear increase with the change-point estimated at 42.97 (1.42) (estimate (SE)) years. Prior to 42.97 years, FSH barely changed; after 42.97 years there was a significant (P less than 0.05) increase in FSH as age increased. Oestradiol levels did not change significantly until an estimated 37.9 years of age, but then decreased significantly (P less than 0.05) with increasing age. Luteal phase Levels of FSH, LH, serum immunoreactive inhibin, oestradiol and progesterone fell slowly with increasing age. There was a significant correlation between serum immunoreactive inhibin with progesterone (r = 0.41, P less than 0.05) but there was no correlation between serum immunoreactive inhibin LH or FSH. CONCLUSION: The results are consistent with a role for serum immunoreactive inhibin, in addition to oestradiol, in the regulation of FSH during the follicular phase of the menstrual cycle as a function of increasing age. This is postulated to reflect diminished folliculogenesis as age progresses with the known decline in the numbers of primordial follicles in the ovary as the menopause approaches. PMID- 1424167 TI - Growth hormone binding protein in Werner's syndrome. AB - OBJECTIVE: GH and growth hormone binding protein in Werner's syndrome were investigated to elucidate their relation to the short stature. DESIGN: The levels of GH binding protein and GH response to insulin-induced hypoglycaemia were determined. GH binding protein levels and its Scatchard analysis in Werner's syndrome were compared with those in normal subjects. PATIENTS: Three patients with Werner's syndrome (one man aged 45 years and two women aged 39 and 38 years) and 41 normal subjects (18 men and 23 women aged 39.3 +/- 5.5 years, mean +/- SD) were studied. MEASUREMENTS: GH binding protein levels were determined using an Ultrogel AcA44 minicolumn and GH levels were measured by a highly sensitive enzyme immunoassay. RESULTS: Two out of three patients with Werner's syndrome had GH binding protein levels above the mean +/- 2SD value in normal subjects. GH secretion was impaired in Werner's syndrome as judged by the low GH response to insulin-induced hypoglycaemia. CONCLUSIONS: Elevated GH binding protein levels may lead to an increase in the bound form of GH, which is probably less bioactive, resulting in growth failure in association with the impaired GH secretion in Werner's syndrome. PMID- 1424168 TI - Preserved thyroidal secretion of thyroxine in acromegalic patients with suppressed hypophyseal secretion of thyrotrophin. AB - OBJECTIVE: We have assessed the mechanisms which maintain euthyroidism in acromegalic patients despite the suppression of thyrotrophin (TSH) secretion. MATERIALS: Fourteen untreated patients with acromegaly were analysed. Ten patients were also studied after pituitary surgery. METHODS: Thyroid hormones, growth hormone (GH), insulin-like growth factor-I (IGF-I) and thyroidal uptake of radioactive iodine, thyrotrophin releasing hormone (TRH) test and basal metabolic rate (BMR) were measured before and after pituitary surgery. RESULTS: Nine patients had palpable goitres. The TSH response to TRH stimulation was suppressed in eight patients, who maintained normal serum levels of total T3, T4 and free T4. The patients with normal TSH response had lower levels of free and total T4 than controls. The response of TSH to TRH correlated inversely with the serum level of total and free T4, and also with the plasma level of IGF-I (r = -0.74, P less than 0.05, n = 9). After pituitary surgery, the serum levels of total and free T4 were elevated for at least up to 6 months, with a decrease in the T3/T4 ratio and the BMR. CONCLUSION: GH may have a direct stimulatory action on the thyroid secretion of T4 possibly via increased IGF-I, despite suppressed TSH secretion. The post-operative elevation of serum T4 suggests the persistent secretion of T4 from the thyroid gland, in spite of instantaneous normalization of the accelerated conversion of T4 to T3, even after reduction of excess GH secretion. PMID- 1424169 TI - Failure of somatostatin analogue to control Cushing's syndrome in two cases of ACTH-producing carcinoid tumours. AB - OBJECTIVE: To determine the effectiveness of somatostatin analogue (octreotide) in controlling hypercortisolism in two patients with ectopic ACTH-producing carcinoid tumours, and to review the literature. DESIGN: The two patients were treated with octreotide administered by subcutaneous injection, for 5 days with 150 micrograms three times daily and for 7 days with 100 micrograms three times daily respectively. They were subsequently treated with oral metyrapone 250 mg three times daily. PATIENTS: Patient 1 had a metastatic carcinoid tumour but the primary was not identified. Patient 2 had a pulmonary carcinoid. Cushing's syndrome due to ectopic ACTH syndrome was established by demonstration of failure of cortisol suppression by dexamethasone, elevated ACTH levels, and immunoperoxidase staining for ACTH within the tumours. MEASUREMENTS: Urinary free cortisol (UFC) was measured on consecutive days during treatment with octreotide. Serum cortisol and ACTH levels were taken daily in patient 2, and on days 0 and 3 in patient 1. RESULTS: Patient 1 had a baseline 24-hour urinary free cortisol of 5340 nmol/24 h, serum cortisol of 915 nmol/l, and serum ACTH of 163 ng/l (ACTH ng/l x 0.23 = pmol/l). After 3 days of octreotide, serum cortisol was 782 nmol/l and ACTH 164 ng/l. Twenty-four hour urinary free cortisol was 4136 nmol/24 h after 7 days of treatment. Metyrapone, however, resulted in a rapid fall in urinary free cortisol to 290 nmol/24 h, with marked clinical improvement. Patient 2 had a baseline 24-hour urinary free cortisol of 2520 nmol/24 h, serum cortisol of 747 nmol/l, and ACTH of 103 ng/l. Urinary free cortisol rose to 2970 nmol/24 h on day 6 of treatment with octreotide. Serum cortisol and ACTH levels fell slightly to 611 nmol/l and 70 ng/l respectively. On changing to metyrapone, the urinary free cortisol fell to 821 nmol/24 h in 4 days. CONCLUSIONS: Octreotide failed to significantly reduce 24-hour urinary free cortisol, serum cortisol and ACTH in the two patients reported. We conclude that it should probably not be regarded as primary treatment for control of hypercotisolism in patients with ACTH-producing carcinoids, but reserved as adjunctive therapy. PMID- 1424170 TI - Efficacy of a new long-acting injectable form of bromocriptine in hyperprolactinaemic patients. AB - OBJECTIVE: The objective of this study was to assess the relationship of different doses of a long-acting bromocriptine preparation (Parlodel LAR) to the degree and duration of PRL suppression. We also measured circulating bromocriptine levels and altered tolerability of the drug. DESIGN: A double-blind randomized study of three different doses 25, 50 and 100 mg of Parlodel LAR. PATIENTS: Twenty-one female patients (seven patients/dose) with both tumoral and non-tumoral hyperprolactinaemia. MEASUREMENTS: After a single injection of Parlodel LAR 25, 50 or 100 mg, serum PRL and plasma bromocriptine levels were assessed during a follow-up of 60 days together with changes in clinical symptoms and signs of hyperprolactinaemia. RESULTS: Serum PRL levels normalized in 19 of 21 patients. The suppression of PRL secretion lasted 28 days in four of seven patients treated with either 25 or 50 mg Parlodel LAR and in five of seven patients who received Parlodel LAR 100 mg. In five of seven patients treated with the 100 mg dose, serum PRL levels were still within the normal range on day 60. Plasma bromocriptine levels remained therapeutically active for 28 days in all three groups. On day 60 they were within the therapeutic range only in the 100 mg group. Clinical data show a rapid disappearance of symptoms and signs of hyperprolactinaemia. Adverse events were mostly mild and transient. CONCLUSIONS: These data support the excellent efficacy and good tolerability of Parlodel LAR in patients with hyperprolactinaemia. PMID- 1424171 TI - Age-related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of bone metabolism in Chinese women. AB - OBJECTIVE: To study the age-related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of calcium metabolism in Chinese women who habitually have a low calcium intake. DESIGN: Cross-sectional study. SUBJECTS: One hundred and fifty-six healthy Chinese women aged 20-83 years. None were on any medication or vitamin supplements. Subjects over the age of 60 years were all living in a hostel; younger subjects were nurses or subjects attending a family clinic for minor illnesses. MEASUREMENTS: Fasting blood and urine samples were collected for biochemical measurements and calcium absorption was measured using 45Ca by the method of Marshall and Nordin. Bone density was measured by dual energy X-ray densitometry (Norland X R20 X-ray bone densitometer) at the left hip and lumbar spine. Serum parathyroid hormone was measured by a chemiluminometric assay. RESULTS: Plasma ionized calcium concentration, alkaline phosphatase, bicarbonate, plasma creatinine and serum B2 microglobulin were significantly higher in the elderly than in the young, whereas plasma phosphate and the anion gap were higher in the young. Urinary excretion of calcium, phosphate and hydroxyproline were all higher in older women. Plasma parathyroid hormone concentration was positively correlated with age even after taking into account the decline in renal function (as indicated by the rise in B2 microglobulin (r = 0.506, P less than 0.001). Serum concentrations of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D were not lower in the older women. Fractional calcium absorption from an oral load of radiolabelled calcium was significantly lower in the older women and 37% of the older women were below the 2.5 percentile found in the younger women. Bone density measured by dual energy X ray densitometry was also significantly lower in the elderly. CONCLUSION: In Chinese women there is an increase in PTH and a decrease in calcium absorption with age in spite of the presence of normal vitamin D metabolites. PMID- 1424172 TI - Circulating immunoreactive inhibin and testosterone levels in men with critical illness. AB - OBJECTIVE: We aimed to concurrently characterize serial changes in circulating immunoreactive inhibin (irINH) and testosterone (T) as reflections of Sertoli and Leydig cell responses to acute critical illness in man. DESIGN: Blood samples were drawn within 24 hours of admission to an Intensive Care Unit and at weekly intervals thereafter for up to 4 weeks while the patient remained in Intensive Care Unit or after discharge to a general ward. PATIENTS: We studied 13 male subjects with critical illness requiring intensive therapy. MEASUREMENTS: Plasma levels of irINH, T, LH, FSH and sex hormone binding globulin (SHBG) were analysed in relation to (i) the severity of illness as indicated by a sepsis score, acute physiology and chronic health evaluation score, and reverse triiodothyronine (rT3) levels and (ii) the outcome of illness as determined by discharge from Intensive Care Unit and the two-month mortality. RESULTS: Overall irINH levels remained normal and correlated negatively with rT3 (r = -0.63, P = 0.001) but not with sepsis, acute physiology and chronic health evaluation score, or gonadotrophin levels. Neither admission nor serial irINH levels significantly distinguished between the different clinical outcomes. In contrast, T levels were depressed and inversely correlated with both sepsis and acute physiology and chronic health evaluation scores (P less than 0.02), and positively with gonadotrophins (P less than 0.01), but not rT3 levels. Men eventually discharged from the Intensive Care Unit showed a rise, while those remaining showed a fall, in T levels (P = 0.02, time-course interaction). Similarly, T levels were lower in patients who died than in survivors, despite the comparable T levels on admission (P = 0.02, time-course interaction). Despite the fall in T levels, gonadotrophin levels remained inappropriately in the eugonadal range but higher in men who were discharged from Intensive Care Unit (P = 0.02, time-course interaction). FSH but not LH levels were correlated with sepsis score (P = 0.02) but not acute physiology and chronic health evaluation score or rT3. CONCLUSIONS: Sertoli cell function as judged by circulating irINH levels is much less affected by acute critical illness than is Leydig cell function as judged by circulating T levels. The suppressive effect of acute critical illness on Leydig cell function is consistent with a hypothalamic-pituitary lesion. PMID- 1424173 TI - Social, educational and vocational status of 48 young adult females with gonadal dysgenesis. AB - OBJECTIVE: The purpose of this study was to evaluate the educational, vocational and social function of young adults with gonadal dysgenesis. DESIGN: Forty-eight female patients with gonadal dysgenesis (17, 45XO; 26, 45XO/46XX or other mosaics; and five pure gonadal dysgenesis) followed by our multidisciplinary team from childhood, were re-evaluated in adult age. RESULTS: Mean age +/- SD at diagnosis was 11.4 +/- 5.0 years and mean age at the time of survey was 29.6 +/- 6.3 years. The mean final height for the patients was 145.5 +/- 8.3 cm (range 134 170 cm). Mean verbal IQ (WISC-R) for the 39 subjects tested was 101.4 +/- 20.7 and mean performance IQ was 86.8 +/- 17.7. No difference in verbal IQ levels was found between the various karyotype groups. Twenty-five had an academic education. All were employed except for one housewife; 37 work in white collar professions. A significant correlation was found between verbal IQ and education (P = 0.005) and between verbal IQ and profession (P = 0.005). Twenty-three served in the army. Fourteen are married: three have an adopted child and two a child born after in vitro fertilization (IVF); others are waiting for IVF or adoption. Five patients had some form of psychiatric problem that required psychiatric or psychological treatment in the past (two had transitory anorexia nervosa and three behavioural problems). Sixty-three per cent reported having wide and satisfactory social relations but limited to female friends. CONCLUSION: Positive adjustment in the professional area and fair adjustment in the social area were not related to physical stigmata or to any other independent variable tested, but rather to intellectual ability and a high degree of achievement motivation. PMID- 1424174 TI - Changes in growth hormone concentrations during puberty in adolescents with insulin dependent diabetes. AB - OBJECTIVE: To document the changes in pulsatile growth hormone secretion in diabetic adolescents during puberty, and to investigate their relationship to both metabolic control and stature. DESIGN: Auxological parameters, overnight growth hormone secretion, fasting IGF-I, hourly glucose and metabolic control were assessed in a group of adolescents with diabetes. PATIENTS: Fifty-two diabetic adolescents (28 males and 24 females) at different pubertal stages and with varying degrees of metabolic control were studied. Ten of those with poor diabetic control were studied on two occasions. MEASUREMENTS: Height and weight measurements, pubertal staging, growth velocity data and bone age estimation were obtained on all the patients. Overnight growth hormone profiles (Pulsar program analysis), glycosylated haemoglobin and fasting IGF-I were performed on all the subjects. Hourly overnight glucose measurements were also obtained on the ten subjects who had two overnight growth hormone studies. RESULTS: For the whole diabetic growth, GH area under curve (AUC) was maximal in late puberty (pubertal stage 4), and was paralleled by maximal GH peak amplitude. No relationship between GH-AUC and metabolic control was demonstrated. No difference in GH parameters was demonstrated between the male and female subgroups. The relationship between growth hormone secretory parameters and stature was not significant. However, GH-AUC was significantly correlated with growth velocity in the males but not the females. CONCLUSIONS: The pattern of GH secretion in adolescents with diabetes parallels that seen in normal adolescents during puberty, with increases in GH concentration associated with increased GH pulse amplitude. The degree of metabolic control had no effect on this pattern and there was no relationship between GH secretory parameters and stature. PMID- 1424175 TI - Abnormalities of intermediary metabolism following a gestational diabetic pregnancy. AB - OBJECTIVE: The aim of this study was to compare intermediary metabolism in glucose tolerant women with previous gestational diabetes and control women without a history of gestational diabetes. SUBJECTS: Fifteen women with previous gestational diabetes and 15 controls individually matched for race, age and body mass index were included. Only subjects with normal glucose tolerance were included in this study. METHODS: Plasma glycerol, 3-OH butyrate, non-esterified fatty acids (NEFA), glucose and insulin were measured fasting and following a 75 g oral glucose load. RESULTS: The women with previous gestational diabetes and their matched controls were of similar racial origin, age and body mass index. There was no difference between those with previous gestational diabetes and controls in fasting glycerol, 3-OH butyrate, NEFA, glucose or insulin concentrations. Following the oral glucose load, glycerol, 3-OH butyrate and NEFA concentrations fell in both groups. However, compared with controls at 120 minutes, those with previous gestational diabetes had significantly higher concentrations of glycerol (median 57, range 24-216 vs 27, range 8-89 mumols/l, P less than 0.005) and 3-OH butyrate (9, range 1-18 vs 5, range 2-11 mumols/l, P less than 0.01). NEFA concentrations were similar in the two groups. Despite similar glucose concentrations during the oral glucose tolerance test the insulin response during the first 60 minutes following oral glucose was significantly reduced in the subjects with previous gestational diabetes when compared with controls (insulin area, 0-60 minutes; 2172, range 788-4767 vs 2830, range 996 4784 pmol min/l, P less than 0.05). CONCLUSIONS: Women with a previous history of gestational diabetes, despite having normal glucose tolerance, have defective insulin release with resultant abnormalities of intermediary metabolism. PMID- 1424176 TI - The importance of adequate serum ferritin levels during oral cyproterone acetate and ethinyl oestradiol treatment of diffuse androgen-dependent alopecia in women. AB - OBJECT: To evaluate the treatment with cyproterone acetate and ethinyl oestradiol of diffuse androgen-dependent alopecia in women. DESIGN: Twenty women were treated for a period of 12 months in a reverse sequential regimen employing cyproterone acetate (CPA, 50 mg once daily from Day 5 to Day 15) and ethinyl oestradiol (EE2, 30 micrograms once daily from Day 5 to Day 24 of the menstrual cycle), and 20 were left untreated and acted as controls. Half of each group had serum ferritin concentrations above or below 40 micrograms/l. PATIENTS: Forty Caucasian premenopausal women aged between 18 and 47 years, presenting with diffuse androgen-dependent alopecia, were enrolled into this study. MEASUREMENTS: Hair variables were assessed initially by the unit area trichogram and again in the same sites 12 months later. Biochemical investigations were performed before treatment and after 3, 6, and 12 months. RESULTS: In the treated group, a significant (P less than 0.01) mean increase in total hair density (hair/cm2) and meaningful hair density (non-vellus hair/cm2) was found in patients in whom the serum ferritin was above, but not below 40 micrograms/l. However, in the control group a significant (P less than 0.05) mean decrease in total hair density and meaningful hair density was observed after 12 months. No correlation between serum ferritin levels and the degree of hair loss within this group could be established. CONCLUSION: Patients treated with the anti-androgen cyproterone acetate and ethinyl oestradiol respond best when serum ferritin is above 40 micrograms/l. PMID- 1424177 TI - Nelson's syndrome following partial pituitary microadenomectomy and pregnancy. AB - We report for the first time the development of Nelson's syndrome in a patient who had previously undergone unsuccessful pituitary microadenomectomy and subsequently bilateral adrenalectomy. The removal of a 3-mm portion of a microadenoma did not protect against the development of Nelson's syndrome within 3 years which was closely related to pregnancy, a previously noted association. This report suggests that the development of Nelson's syndrome depends not on the size of the initial pituitary tumour but rather on its individual potential for proliferating once free of the inhibitory effects of glucocorticoid excess. PMID- 1424178 TI - Post-prandial thermogenesis and insulin sensitivity in the polycystic ovary syndrome. PMID- 1424179 TI - Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance. AB - OBJECTIVE: In order to investigate the possible causes and effects of obesity in polycystic ovary syndrome resting energy expenditure, postprandial thermogenesis and insulin resistance were measured in 14 polycystic ovary syndrome subjects and in 14 controls. DESIGN: A cross-sectional study of a selected group of patients was performed. PATIENTS: Seven of the PCOS subjects were obese and seven lean. Controls were individually matched for age, race, weight, body mass index (BMI) lean body mass and percentage fat. The obese, but not lean, polycystic ovary syndrome subjects had a greater waist:hip ratio than controls (median (range) obese PCOS 0.865 (0.823-0.960) vs obese control 0.804 (0.823-0.940), P less than 0.025). MEASUREMENTS: Metabolic rate was measured by continuous indirect calorimetry and insulin sensitivity was assessed by a short insulin tolerance test. RESULTS: The resting energy expenditure (REE) was similar in PCOS subjects and controls (median (range), 6796 (5489-7774) vs 6833 (4893-8492) kJ/day). REE correlated with LBM in the PCOS group (r = 0.83, P less than 0.00) and the control group (r = 0.82, P less than 0.001). Postprandial thermogenesis was reduced in polycystic ovary syndrome (obese: median 45.4 (range 33.6-100.0) vs 86.5 (67.2-109.2) kJ (P less than 0.05); lean: 79.4 (73.5-108.4) vs 89.9 (76.0 109.2) kJ (P less than 0.05). Fasting insulin (9.7 +/- 3.6 vs 4.4 +/- 0.8 mU/l, P less than 0.05) and postprandial incremental insulin rise (163 +/- 31 vs 116 +/- 15 mU/l, P less than 0.025) were higher in polycystic ovary syndrome. Insulin sensitivity was reduced in polycystic ovary syndrome (obese: median 136 (range 92 169) vs 173 (109-225) mumol/l/min (P less than 0.05); lean: 161 (138-225) vs 194 (161-253) mumol/l/min (P less than 0.05)). The reduction in insulin sensitivity correlated with the reduced postprandial thermogenesis in the polycystic ovary syndrome group (r = 0.75, P less than 0.01). CONCLUSION: These results confirm previous reports of hyperinsulinaemia and insulin resistance in polycystic ovary syndrome. Furthermore, polycystic ovary syndrome subjects have a reduced postprandial thermogenesis which is related statistically to the reduced insulin sensitivity. The decreased postprandial thermogenesis may predispose women with polycystic ovary syndrome to weight gain. PMID- 1424180 TI - Increased free testosterone but normal 5 alpha-reduced testosterone metabolites in obese premenopausal women. AB - OBJECTIVE: The aim of the study was to investigate whether the absence of increased 5 alpha-reductase activity explained the absence of hirsutism in premenopausal obese women with increased free testosterone (FT) levels. DESIGN: As in hyperandrogenicity there generally exists evidence for increased 5 alpha reductase activity, we measured, as parameters of 5 alpha-reductase activity, plasma levels of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide (ADG) and androsterone glucuronide (ADTG) as well as their precursor levels in obese women without hirsutism, obese hirsute women, non-obese hirsute women, and non-obese, non-hirsute women. PATIENTS: Eighty-two premenopausal women (20-45 years old) were studied, in four age matched groups: 39 controls, 18 obese without hirsutism, 11 non-obese hirsute and 14 obese hirsute women. MEASUREMENTS: Blood samples were taken between days 5 and 7 of the menstrual cycle. Steroid hormone levels were measured by radioimmunoassay. Free testosterone levels were measured by equilibrium dialysis. RESULTS: Compared to controls, mean free testosterone levels were increased (P less than 0.01) in obese, obese hirsute and hirsute patients, whereas mean DHEAS levels were increased in hirsute and obese hirsute (P less than 0.01), but not in obese, women. Mean androstanediol glucuronide levels were markedly increased in hirsute and obese hirsute patients (P less than 0.01), but not in obese women. Plasma androsterone glucuronide levels were increased in hirsute (P less than 0.01), in the normal range in obese hirsute, and decreased in obese women (P less than 0.01). CONCLUSIONS: These results show that, despite the presence of higher free testosterone levels, neither 5 alpha reductase activity (as suggested by normal androstanediol glucuronide levels) nor adrenal androgen precursor levels (DHEAS) are increased in obese women without hirsutism. PMID- 1424181 TI - 17 beta-Oestradiol, androstenedione and inhibin levels in fluid from individual follicles of normal and polycystic ovaries, and in ovaries from androgen treated female to male transsexuals. AB - OBJECTIVE: The aim was to monitor carefully follicular growth arrest in polycystic ovaries by assay of hormones in individual follicles. DESIGN AND PATIENTS: Fluid from follicles less than or equal to 10 mm was obtained from ovaries of 16 regularly cycling women between days 1 and 12 of the follicular phase (controls, n = 120 follicles), polycystic ovaries of five women with polycystic ovary syndrome (n = 43), and polycystic ovaries from 14 long-term testosterone treated female to male transsexuals (n = 120). MEASUREMENTS: Fluid was assayed for oestradiol, androstenedione, and immunoactive inhibin. Luteinizing hormone, follicle-stimulating hormone, and testosterone levels were estimated in serum. RESULTS: Median serum LH was lower in transsexuals than in controls (P less than 0.05), and in polycystic ovary syndrome (P less than 0.01). Median serum testosterone was not significantly different between polycystic ovary syndrome and transsexuals, and was elevated in both groups as compared to controls (P less than 0.01). Oestradiol was present in all follicles obtained from polycystic ovaries of polycystic and transsexual patients, in which no follicle greater than 10 mm could be detected. In the three groups, between patient differences in mean oestradiol, androstenedione, inhibin, and androstenedione/oestradiol ratio were significantly larger than expected in view of the variation between follicles within individuals. Taking into account this between-patient difference, no significant differences could be established between the three groups for all endocrine parameters. The percentage of presumed healthy follicles (androstenedione/oestradiol ratio less than or equal to 4) was 12% in controls, 17% in polycystics, and 14% in transsexuals, and was not significantly different between groups. CONCLUSIONS: The results may indicate that (1) abnormally high circulating androgen concentrations with or without elevated LH levels disturb the process of selection, and could therefore play a role in the pathogenesis of polycystic ovaries; (2) in polycystic ovaries from polycystic ovary syndrome and transsexual patients, aromatase activity is present in vivo in small antral follicles, and the proportion of presumed healthy follicles is not different from that encountered in normal ovaries; (3) oestradiol levels are not different between non-dominant follicles of normal and polycystic ovaries, suggesting that only enhancement of aromatase activity by FSH may be disrupted in polycystic ovaries, (4) because androstenedione levels are not different comparing follicles of normal and polycystic ovaries, hyperandrogenaemia in the syndrome seems to originate from the abnormally high number of cystic atretic follicles generally observed in polycystic ovaries; (5) marked variation in the endocrine follicular microenvironment within and between women precludes pooling fluid from several follicles. PMID- 1424182 TI - The effect of iodide on serum thyroid hormone levels in normal persons, in hyperthyroid patients, and in hypothyroid patients on thyroxine replacement. AB - OBJECTIVE: To clarify the duration and the extent of the antithyroid effect of iodides in hyperthyroidism, and to investigate whether iodides have an additional peripheral effect on the metabolism of thyroid hormones, as has been reported for some organic iodine compounds. DESIGN: The effect on the peripheral thyroid hormone levels of 150 mg of potassium iodide daily (equivalent to 114 mg of iodide) for 3-7 weeks was compared in 21 hyperthyroid patients and 12 healthy controls. A possible effect of iodide on the peripheral metabolism of thyroid hormones was investigated by assessing the serum levels of thyroid hormone in 12 hypothyroid patients on thyroxine replacement for 2 weeks. PATIENTS: There were 21 thyrotoxic patients, 12 healthy hospital controls, and 12 patients with complete or near-complete hypothyroidism, on thyroxine replacement. MEASUREMENTS: The following were measured before and at weekly intervals after iodide administration: (1) pulse rate, (2) serum T4, (3) serum T3, (4) serum TSH, (5) serum thyroxine-binding capacity (TBC), (6) serum rT3, (7) serum thyroxine binding globulin (TBG), (8) the free-T4 Index, calculated as T4/TBC. RESULTS: In the hyperthyroid patients serum T4, T3 and rT3 decreased, whereas serum thyroxine binding globulin and thyroxine binding capacity increased. Serum T3, however, did not become completely normal in all cases. After 21 days, serum T4 and T3 started increasing again in some cases, but other patients remained euthyroid even after 6 weeks. In the normal controls there was a small but significant and consistent decrease in serum T4, T3 and rT3 and an increase in serum TSH. Finally, in the T4 treated hypothyroid patients there was no consistent change, except for an increase of serum T4 at 1 and 14 days and a decrease of serum TSH the first day. CONCLUSION: Iodides in hyperthyroidism have a variable and unpredictable intensity and duration of antithyroid effect. Their antithyroid effect is smaller in normal controls. They have no important effect on the peripheral metabolism of thyroid hormones. PMID- 1424183 TI - Effect of selenium supplementation on thyroid hormone metabolism in an iodine and selenium deficient population. AB - OBJECTIVE: Severe selenium deficiency has been documented in northern Zaire, already known as one of the most iodine deficient regions in the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted in this area to evaluate the effects of a selenium supplementation on thyroid diseases. DESIGN: Placebo or selenium 50 micrograms as selenomethionine was administered once daily for 2 months. Blood and urine samples were collected before and after supplementation. PATIENTS: Fifty-two healthy schoolchildren from northern Zaire. MEASUREMENT: Selenium status, thyroid function and urinary iodide were determined. RESULTS: After 2 months of selenium supplementation, mean +/- SD serum T4 decreased from 73.1 +/- 45.4 to 48.3 +/- 23.7 nmol/l (P less than 0.001), serum FT4 from 11.8 +/ 6.7 to 8.4 +/- 4.1 pmol/l (P less than 0.01), and serum rT3 from 124 +/- 115 to 90 +/- 72 pmol/l (P less than 0.05), without significant change in serum T3 and serum TSH. CONCLUSION: Deiodinase type I which has been shown to be a seleno enzyme could account for the changes in thyroid hormones in our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism in humans. Selenium could be an important cofactor in the clinical picture of iodine deficiency in Central Africa and could be involved in the aetiology of both forms of cretinism. PMID- 1424184 TI - Pulsatile growth hormone release in normal women during the menstrual cycle. AB - OBJECTIVE: We sought to characterize pulsatile growth hormone (GH) release in normal women during the menstrual cycle and to document possible relationships between such characteristics and concentrations of 17 beta-oestradiol and progesterone. SUBJECTS: Fifteen women with ostensibly normal menstrual function were studied during the early follicular phase, 15 during the late follicular phase and 15 during the mid-luteal phase of the menstrual cycle. DESIGN: The phase of the menstrual cycle having been documented, blood samples were obtained from each woman every 10 minutes for 24 hours. MEASUREMENTS: Serum GH was measured in each sample by immunoradiometric assay. Pulsatile GH release was appraised utilizing the objective, statistically-based pulse detection algorithm Cluster. RESULTS: The mean (+/- SEM) integrated serum GH concentration (mU/l min) in late follicular phase women (5335 +/- 848) was higher than that observed in early follicular phase women (3156 +/- 322; P = 0.032). The integrated GH concentration calculated for mid-luteal phase women (3853 +/- 788) was intermediate between but not statistically different from that observed in early follicular (P = 0.48) and late follicular (P = 0.14) phase women. No differences in GH pulse frequency (pulses/24 hours) were found among early follicular (8.27 +/- 0.55), late follicular (7.93 +/- 0.91) or mid-luteal (8.47 +/- 0.66) phase women. Mean maximal GH pulse amplitude (mU/l) was higher in late follicular phase (8.93 +/- 1.00) than early follicular phase (5.74 +/- 0.67; P = 0.008) and mid luteal phase (5.76 +/- 0.74; P = 0.008) women. Similarly, incremental GH pulse amplitude (mU/l) was higher in late follicular phase (7.33 +/- 0.83) than early follicular phase (4.68 +/- 0.58; P = 0.005) and mid-luteal phase (4.36 +/- 0.39; P = 0.002) women. No differences in mean pulse widths or in the interpeak valley mean GH concentrations were found among the groups. Multiple regression of each pulse parameter against serum concentrations of testosterone, 17 beta-oestradiol and progesterone revealed a significant (P = 0.045) positive correlation between maximum GH pulse amplitude and oestradiol and a significant (P = 0.04) negative correlation between maximal GH pulse amplitude and progesterone (r = 0.41). CONCLUSION: These results suggest that late follicular phase concentrations of oestradiol may enhance circulating GH via an amplitude-modulated rather than a frequency-modulated effect on the endogenous GH pulse. Progesterone may blunt this oestrogen-associated effect, thus resulting in the observed mid-luteal phase concentrations of GH. Whether these gonadal hormones act primarily at the hypothalamus and/or anterior pituitary gland remains to be clarified, but the present observations indicate that pulsatile GH release throughout the normal menstrual cycle is significantly amplitude regulated. PMID- 1424186 TI - Acromegaly and its treatment in the McCune-Albright syndrome. AB - The McCune-Albright syndrome, comprising polyostotic fibrous dysplasia, cutaneous pigmentation and endocrine hyperfunction, is occasionally complicated by acromegaly due to a pituitary adenoma. We report a patient with the McCune Albright syndrome and acromegaly, who developed secondary hypothyroidism and hypoadrenalism, in whom surgical removal of the pituitary tumour was technically difficult. A combination of a long-acting somatostatin analogue ('Sandostatin') and external irradiation were therefore used as treatment. PMID- 1424185 TI - Expression of the neuroendocrine cell marker 7B2 in human ACTH secreting tumours. AB - OBJECTIVE AND DESIGN: Pro-opiomelanocortin gene expression is a ubiquitous phenomenon which takes place not only in the pituitary but also in many normal and tumoral non-pituitary tissues. However, the clinical features of the ectopic ACTH syndrome are rarely encountered. To further investigate this problem we examined series of normal human pituitaries and endocrine tumours evaluating the tissue content of pro-opiomelanocortin peptides, and the state of neuroendocrine differentiation as indicated by the biochemical marker 7B2. PATIENTS AND MEASUREMENTS: Tissue concentration of 7B2, pro-opiomelanocortin products (joining peptide and beta-endorphin) were measured in 13 pituitary corticotrophic adenomas and 13 non-pituitary tumours associated with the ectopic ACTH syndrome (five out of 20 bronchial carcinoid tumours, two out of 19 phaeochromocytomas, one out of 11 medullary thyroid carcinomas, three pancreatic and two thymic carcinoid tumours). Molecular weight forms of immunoreactive 7B2 and 7B2 RNA messenger were determined using Western and Northern blot analysis respectively. RESULTS: In all tissues examined, concentrations of immunoreactive beta-endorphin (fmol/mg tissue wet weight) showed widely distributed values from less than 0.7 to 1,340,000, which were correlated (r = 0.975, P less than 0.01) with that of immunoreactive joining peptide, another pro-opiomelanocortin fragment. In the 13 non-pituitary tumours associated with the ectopic ACTH syndrome, immunoreactive beta-endorphin concentrations ranged from 8.6 to 548,000, whereas in normal and tumoral pituitaries they varied from 16,600 to 364,800, and 5000 to 1,340,000, respectively. Immunoreactive 7B2 was detected in 67 of 68 neuroendocrine tumours. Tissue concentrations (fmol/mg tissue wet weight) of immunoreactive 7B2 varied from 135 to 1787 in pituitary tumours; from less than 0.5 to 555 in bronchial carcinoids; from 21.7 to 793 in phaeochromocytomas; from less than 1.6 to 948 in medullary thyroid carcinomas. Western blot analysis showed a predominant molecular weight form of immunoreactive 7B2 at 22 kDa. Northern blot analysis of RNA extracted from ACTH secreting pituitary and non-pituitary tumours showed a predominant signal hybridizing at 1.5 kb with a 7B2 probe. CONCLUSION: These results show that all ACTH secreting tumours have biochemical markers for neuroendocrine differentiation. Tissue concentrations of pro-opiomelanocortin peptides are variable, being extremely high in the most benign tumours and low in those with an aggressive growing pattern, and are not correlated with the biochemical neuroendocrine markers. PMID- 1424187 TI - The therapeutic potential of recombinant human insulin-like growth factor-I. PMID- 1424188 TI - The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency. AB - OBJECTIVE: We wished to assess the effect of changes in the plasma concentration of 1,25-dihydroxyvitamin D on the plasma elimination half-time for 25 hydroxyvitamin D in man. DESIGN: The turnover of 25-hydroxyvitamin D in plasma was investigated after intravenous doses of the radioactively labelled metabolite had been given to a group of patients (n = 17) with disorders of bone and mineral metabolism before and after oral treatment with calcium or 1,25-dihydroxyvitamin D. PATIENTS: Seven patients with post-menopausal osteoporosis, five with hypoparathyroidism, three with hypophosphataemic osteomalacia, one with renal osteodystrophy and one patient with coeliac disease were studied. MEASUREMENTS: Intravenous injections of 3H-labelled 25-hydroxyvitamin D were given and plasma elimination half-time assessed over periods of 4-14 days during which frequent measurements of plasma calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were made. Changes in the plasma elimination half time for 3H-25-hydroxyvitamin D before and after treatment with calcium and 1,25 dihydroxyvitamin D were evaluated by non-parametric statistical analysis. RESULTS: The elimination half-time for 3H-25-hydroxyvitamin D in plasma was significantly shortened by raising the circulating concentration of 1,25 dihydroxyvitamin D. Conversely, in a patient with intestinal malabsorption of calcium, the metabolic clearance of 3H-25-hydroxyvitamin D was prolonged when the concentration of 1,25-dihydroxyvitamin D in plasma was decreased by suppressing secondary hyperparathyroidism with large calcium supplements. In the longer-term studies (n = 10) there was a highly significant inverse relation (r = -0.88, P < 0.001) between the change in the plasma concentration of 1,25-dihydroxyvitamin D and the induced change in the elimination half-time of 3H-25-hydroxyvitamin D. There was also a significant correlation (r = 0.66, p < 0.0025) between the observed fall in the plasma concentration of unlabelled 25-hydroxyvitamin D and the predicted fall calculated from the measured value for the half-time of the 3H labelled metabolite. In acute studies in patients with post-menopausal osteoporosis (n = 7), enhanced metabolic inactivation of 3H-25-hydroxyvitamin D was detectable within 24 hours of oral administration of 1,25-dihydroxyvitamin D. CONCLUSIONS: The effect of 1,25-dihydroxyvitamin D on the catabolism of 25 hydroxyvitamin D can contribute to the development of vitamin D deficiency in many clinical disorders. When the natural supply of vitamin D is limited by sunlight deprivation, a sustained increase in the plasma concentration of 1,25 dihydroxyvitamin D due to primary or secondary hyperparathyroidism will lead to accelerated depletion of vitamin D stores. PMID- 1424189 TI - Cardiac conduction in patients with hypercalcaemia due to primary hyperparathyroidism. AB - OBJECTIVE: To assess whether hypercalcaemia due to primary hyperparathyroidism is associated with significant cardiac arrhythmias. DESIGN AND PARTICIPANTS: The prevalence of cardiac arrhythmias and conduction disturbances was evaluated by 12 lead ECG and 24-hour long-term ECG during pre-surgical hypercalcaemia and after post-surgical normalization of serum calcium values in 20 patients with primary hyperparathyroidism. RESULTS: After surgery, mean +/- SD calcium levels decreased from 2.85 +/- 0.1 to 2.40 +/- 0.1 mmol/l (P < 0.001). There was a significant increase in QT-intervals (0.36 +/- 0.05 vs 0.39 +/- 0.05) and QTc-intervals (0.38 +/- 0.04 vs 0.42 +/- 0.03) after surgery (P < 0.01). Long-term ECG showed no change in the minimal heart rate 47 +/- 8 vs 48 +/- 7 beats/min or in the longest RR interval 1.6 +/- 0.5 vs 1.6 +/- 0.5 s (P NS). There was no difference in the prevalence of supraventricular or ventricular arrhythmias. No episode of high grade AV-block was observed before surgery. Circadian heart rate rhythm did not change between investigations. CONCLUSIONS: It is concluded that moderate hypercalcaemia, in spite of causing a shortening of the repolarization phase (QT interval), has no clinically significant effect on cardiac conduction. PMID- 1424190 TI - Peripheral bone density in women with untreated multinodular goitre. AB - OBJECTIVES: We wished to determine whether women with multinodular goitre and spontaneous subclinical hyperthyroidism have decreased bone density. DESIGN AND SUBJECTS: Bone density was measured at the distal and proximal forearm. Data were expressed as Z-scores relative to the mean values out of 125 control subjects matched for age and menopause. The Z-scores of 23 women with subclinical hyperthyroid goitre (TSH < 0.1 mU/l and normal values for FT4 and total T3) and of 54 women with euthyroid goitre were compared. MEASUREMENTS: Bone density was measured by single photon absorptiometry. TSH was measured by IRMA, FT4 by RIA. RESULTS: Relative to the euthyroid goitre subjects the mean +/- SEM Z-scores of both the distal and proximal forearm density were lower (-0.69 +/- 0.17 vs -0.1 +/- 0.18, P < 0.05 and -0.5 +/- 0.18 vs 0.07 +/- 0.18, P < 0.05, respectively). Median (range) FT4 in the subclinical hyperthyroid goitre subjects was significantly higher than euthyroid goitre subjects (15.6 (11-23.2) pmol/l vs 11.9 (8.3-18.3) pmol/l, P < 0.001) although still within the normal range. FT4 correlated inversely with Z-scores of both distal and proximal forearm bone density in the subjects with subclinical hyperthyroidism (r = -0.42, P < 0.05 and r = -0.43, P < 0.05, respectively), but not in the euthyroid goitre subjects. CONCLUSION: These findings indicate that women with untreated multinodular goitre and subclinical hyperthyroidism have reduced bone density in the forearm. PMID- 1424191 TI - Comparison of methods for the determination of unbound triiodothyronine in pregnancy. AB - OBJECTIVE: To study the changes in unbound T3 concentration in the first trimester of pregnancy. DESIGN: We measured serum unbound T3 concentration before and after termination of pregnancy. PATIENTS: Twenty-six clinically euthyroid women. MEASUREMENTS: We used one non-analogue assay (Sclavo) and three analogue assays (Amersham, Becton Dickinson and Diagnostic Products Corporation). RESULTS: Regression analysis did not show any significant agreement between the analogue and non-analogue assays. After termination of pregnancy, unbound T3 concentration as measured by Sclavo and Amersham assays did not change whereas unbound T3 concentration increased and decreased as measured by Becton Dickinson and Diagnostic Products assays respectively. Changes were not directly related to albumin or thyroid binding globulin. CONCLUSION: We believe unbound T3 concentrations as measured by the analogue assays used in this study are due to a balance of errors and cannot be used to determine true physiological changes in pregnancy. PMID- 1424192 TI - Effect of menopause and hormone replacement therapy on urinary excretion of pyridinium cross-links: a longitudinal and cross-sectional study. AB - OBJECTIVE: To study longitudinally the effect of the menopause and hormone replacement therapy on the new markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN AND PATIENTS: Urinary pyridinoline and deoxypyridinoline were measured every 3 months for 2-3 years in 15 healthy women aged 45-54 years. Nine remained premenopausal and six became post-menopausal during the study. Urinary pyridinoline and deoxypyridinoline were also measured before and after 3 months of either placebo or hormone replacement therapy in 65 post-menopausal women, aged 45-54 years, who were participating in a double-blind study. MEASUREMENTS: Urinary pyridinoline and deoxypyridinoline were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion. RESULTS: Urinary pyridinoline and deoxypyridinoline remained almost constant during the premenopausal period. Both started to increase 6 months after the last menstrual bleeding and the mean post-menopausal values were 30-50% higher than the premenopausal values in the same subjects (values in nmol/mmol creatinine given as mean +/- SEM: urinary pyridinoline (premenopausal) = 29 +/- 2 vs urinary pyridinoline (post-menopausal) = 38 +/- 6, P < 0.05; urinary deoxypyridinoline (premenopausal) = 8 +/- 1 vs urinary deoxypyridinoline (post-menopausal) = 12 +/- 1, P < 0.05). Three months of post-menopausal hormone replacement therapy decreased (P < 0.001) both to premenopausal levels. CONCLUSION: Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hormone replacement therapy. PMID- 1424193 TI - Regulation by glucocorticoids of interferon gamma-induced HLA-DR antigen expression in cultured human orbital fibroblasts. AB - OBJECTIVE: The purpose of this study was to determine whether glucocorticoids can block the induction of HLA-DR antigen expression by interferon gamma in human fibroblasts in culture. DESIGN AND PATIENTS: Confluent cultures of fibroblasts derived from the orbit or the skin of patients with Graves' ophthalmopathy or from normal subjects were treated with interferon gamma (100 U/ml) without or with graded concentrations of steroids. MEASUREMENTS: Cultures were analysed for HLA-DR expression using quantitative immunoblotting and indirect immunofluorescence. RESULTS: Glucocorticoids could block HLA-DR induction in a dose-dependent manner. At 10(-6) mol/l, the steroids dexamethasone and RU 28362 inhibited expression by 70% (P < 0.004) and 56% (P < 0.002) respectively. RU 38486, a glucocorticoid antagonist, could reverse the effect of both glucocorticoids, an action that was also dose dependent. At 10(-5) mol/l, RU 38486 blocked virtually the entire glucocorticoid effect. CONCLUSIONS: These results suggest that glucocorticoids can regulate HLA-DR induction by interferon gamma at physiological concentrations, an action which is stereospecific and mediated through the glucocorticoid receptor. PMID- 1424194 TI - Frequency of prolactin pulsatile release in normal men and in agonadal patients is neither coupled to LH release nor influenced by androgen modulation. AB - OBJECTIVE: We wished to examine and characterize the prolactin pulsatile secretory pattern in both normal and agonadal males in order to assess whether there was any concordance with LH secretion. DESIGN: Patients were sampled every 5 minutes for 12 hours. PATIENTS: We studied five normal and four agonadal men, the latter group before and on testosterone enanthate (TE) (200 mg i.m. every 15 days) treatment. MEASUREMENTS: Prolactin and luteinizing hormone plasma levels were determined using commercial RIA systems. Pulse detection was performed using the DETECT program and the degree of concordance between luteinizing hormone and prolactin was established computing the specific concordance index. RESULTS: We demonstrated the presence of a frequent PRL secretory pattern in normal men (22.8 +/- 1.8 peaks/12h; mean +/- SEM) and in agonadal patients, both in basal conditions and during testosterone treatment (20.5 +/- 2.8 and 18 +/- 1.6 peaks/12h, respectively). The testosterone treatment in agonadal men significantly reduced luteinizing hormone pulse frequency (baseline: 27.5 +/- 2, testosterone administration: 18 +/- 1.3 peaks/12h, P < 0.01) but did not affect pulsatile prolactin release. Using a 10 and 15 minute sampling protocol, we observed that prolactin pulse frequency significantly decreased (P < 0.01) and was similar to the frequencies estimated in previous reports. When luteinizing hormone and prolactin time series were studied to evaluate the possible presence of a specific concordance (SC) between the secretory events of the two hormones, no significant degree of concomitancy was observed neither using the specific concordance index or the cross-correlation analysis. CONCLUSIONS: This report demonstrates (a) the presence of frequent pulsatile release of prolactin in both controls and agonadal patients (baseline and on testosterone enanthate), (b) the use of an appropriate sampling interval (5 minutes) to unmask the prolactin pulsatile release, (c) that in men, luteinizing hormone secretory events are not temporally linked to prolactin secretion, and (d) that androgens, even if reducing luteinizing hormone pulse frequency in agonadal patients, do not significantly affect prolactin pulsatile secretion, suggesting that testosterone and its metabolites do not affect lactotroph activity. PMID- 1424195 TI - Luteinizing hormone response to clomiphene citrate in central precocious puberty. AB - OBJECTIVE: The aim of the present study was to determine the LH response to clomiphene citrate administration in children with central precocious puberty and different bone ages to gain insight into the hypothalamic maturation mechanism. PATIENTS AND METHODS: Twelve children with untreated central precocious puberty were studied. Five had central nervous system lesions and seven had idiopathic central precocious puberty. Their chronological and bone ages ranged from 1.7 to 8.8 years and 3.5 to 13.5 years, respectively. Clomiphene citrate (3 mg/kg/day) was administered orally for 7 days. Blood samples were collected on days 0, 6 and 8. LH and FSH were determined by RIA. The results were compared with GnRH responses or with bone age. RESULTS: No increase over basal LH levels was detected in four patients, but increased LH levels were detected in the remaining eight during clomiphene administration. The shift from negative to positive responses was around 8-9 years bone age. The sum of LH responses (days 6 and 8) to clomiphene citrate, and particularly the 8th-day LH levels, were significantly correlated with their respective bone age (r = 0.83). However, the LH responses to GnRH were not significantly correlated with bone age or with LH responses to clomiphene. CONCLUSIONS: This study shows that the LH responsiveness to clomiphene citrate in central precocious puberty increases with skeletal maturation, indicating that the activation of the hypothalamic pubertal mechanism in central precocious puberty may progress in a gradual sequence. These changes in LH response to clomiphene in central precocious puberty mimic those observed with the development of normal puberty, but occur at a much earlier age. PMID- 1424196 TI - The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. AB - OBJECTIVE: The effect on bone, protein, carbohydrate and lipid homeostasis as well as body composition of the administration of growth hormone to adult patients with growth hormone deficiency was studied. DESIGN: Growth hormone was administered at a dose of 25 micrograms/kg/day with a maximum of 1.48 mg (4 IU) a day, for 6 months in eight adults. Studies were done before the start and at 1, 3 and 6 months during therapy, as well as 3 months after treatment had been stopped. RESULTS: Subjective well-being as assessed by a short psychological tests showed an improvement in six and no change in two patients. Body composition, as assessed by body impedance assessment and D2O dilution, both showed an increase in lean body mass of 4 kg (5% of body weight), accompanied by a decrease in mean fat mass of 3 kg. Nitrogen turnover studies showed a transient increase in fed state nitrogen balance due to an increase in the rate of protein synthesis, which exceeded a smaller increase in the protein degradation rate. Growth hormone treatment did not affect the circulating levels of 25(OH)-vitD or PTH 1-84, while 1,25(OH)2-vitD had significantly increased after 6 months, as well as 3 months after treatment ended. Osteocalcin, procollagen I levels, as well as 24-hour urinary excretion of hydroxyproline and calcium rose during growth hormone administration but subsequently decreased rapidly after administration had been stopped, while the increase in alkaline phosphatase persisted. This increase in markers of both bone resorption and bone formation indicates an activation of bone remodelling, but this was not reflected by an increase in bone density. Glucose levels, measured before and during a normal breakfast, increased during growth hormone treatment, but serum insulin levels did not. Total cholesterol levels decreased by 0.5 mmol/l. Levels of T4 and free T4 as well as rT3 decreased, while T3 increased during growth hormone treatment. CONCLUSION: Therapy with growth hormone for 6 months in a dose varying between 6 and 25 micrograms/kg/day increased lean body mass and decreased fat mass. The sense of general well-being improved in most patients. Furthermore, growth hormone treatment increased bone turnover without a measurable increase in bone density, caused some minor changes in lipid and carbohydrate metabolism, and increased the metabolism of thyroxine to T3. PMID- 1424197 TI - The use of the polymerase chain reaction in prenatal diagnosis of growth hormone gene deletions. AB - OBJECTIVE: Familial isolated growth hormone deficiency (IGHD) type IA is characterized by a complete absence of human growth hormone (hGH) resulting in most cases from either a 6.7 or 7.7 kb deletion of DNA containing the hGH-1 gene. These patients have a strong initial anabolic response to exogenous recombinant hGH (r-hGH) therapy, frequently associated with the development of immune intolerance to r-hGH which causes an arrest of response to r-hGH replacement. This disorder is inherited as an autosomal recessive trait. PATIENTS AND DESIGN: In two pregnancies at risk, the polymerase chain reaction (PCR) was applied as a method for identifying hGH-1 gene deletions in DNA obtained by chorionic villus sampling (CVS) in the first trimester. RESULTS: Homozygotes for the 6.7kb deletion of DNA containing the hGH-1 gene were easily and conclusively detected by the absence of 1900, 761 and 712bp fragments after SmaI digestion of the polymerase chain reaction products. In contrast, the pattern found in heterozygotes for the hGH-1 gene deletion was difficult to distinguish from the pattern found in normal homozygotes. CONCLUSIONS: We conclude that the polymerase chain reaction method is valuable for diagnosing individuals who are homozygous for hGH-1 gene deletions, while heterozygotes and normal individuals may be difficult to distinguish from each other. We suggest that, in these cases, Southern blotting remains the analysis to perform. PMID- 1424198 TI - Endocrine dysfunction in Kearns-Sayre syndrome. AB - Kearns-Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction. Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperaldosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroidism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroidism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroidism was found. PMID- 1424199 TI - Oestrogen therapy for girls with tall stature. PMID- 1424200 TI - Molecular genetics, hypogonadism and luteinizing hormone. PMID- 1424201 TI - High serum sex hormone-binding globulin (SHBG) in premature thelarche. AB - OBJECTIVE: We determined serum sex hormone-binding globulin (SHBG), serum dehydroepiandrosterone sulphate, serum oestradiol and serum testosterone and its fractions in girls with premature thelarche. DESIGN: Blood was drawn from girls with recently diagnosed (3-12 weeks) premature thelarche. Serum was kept frozen for at least one year before hormonal determination to exclude precocious puberty by clinical evaluation. PATIENTS: Seventeen girls with premature thelarche aged 0.83-7.16 years were studied, and compared with a group of 22 normal prepubertal girls. MEASUREMENTS: SHBG was measured by saturation analysis and serum dehydroepiandrosterone sulphate, serum total oestradiol and serum total testosterone were determined by radioimmunoassay. Non-SHBG-bound testosterone and free testosterone were calculated from an equation derived from the law of mass action. RESULTS: Median serum SHBG in premature thelarche was 137 nmol/l (range 64-221), significantly higher than in normal controls, 93.7 (32-172) (P < 0.05) non-parametric test of medians. Serum SHBG decreased significantly with age in controls but not in premature thelarche. No difference was found in serum dehydroepiandrosterone sulphate. Median serum total testosterone (0.34 nmol/l, 0.17-0.97), median serum non-SHBG-bound testosterone (0.04 nmol/l, 0.02-0.10) and median free testosterone (2.2 pmol/l, 1.0-4.5) were significantly lower in premature thelarche than in control (P < 0.001). CONCLUSIONS: Serum SHBG is high and bioavailable T is low in girls with premature thelarche. This might alter the oestrogen/androgen ratio in the breast. PMID- 1424202 TI - Effects of oral testosterone undecanoate on growth, body composition, strength and energy expenditure of adolescent boys. AB - OBJECTIVE: We determined the effect of 3 months of daily, 40 mg oral testosterone undecanoate on growth, body composition, hand grip and quadriceps muscle strength, and total free-living daily energy expenditure in boys with constitutionally delayed puberty. DESIGN: Double blind, placebo controlled study. PATIENTS: Eighteen boys with constitutionally delayed puberty, mean (SD) age 13.2 (1.6) years. MEASUREMENTS: Body composition measurements were made by skinfold thickness, bioelectrical impedance and stable isotope dilution (H2(18)O) methods. Energy expenditure was assessed by the doubly-labelled water (2H2(18)O) technique. RESULTS: Height velocity increased from 5.4 (0.8) to 8.1 (0.6) cm/year (P < 0.05) in the 3 months after active therapy. Fat-free mass increased more with therapy (2.7 (0.3) kg) over the 6-month study period than with placebo (1.7 (0.4) kg, P < 0.5). Height velocity increases correlated with daily increases in fat-free mass (r = 0.68, P = 0.005) in the study group as a whole. Energy expenditure and muscle strength increased similarly in both groups. Predicted adult height decreased in the group which was treated with testosterone undecanoate. CONCLUSIONS: Testosterone undecanoate (40 mg daily for 3 months) significantly increased height velocity and fat-free mass velocities after 6 months but not muscle strength, endurance or total daily energy expenditure. PMID- 1424203 TI - Point mutations detected in the androgen receptor gene of three men with partial androgen insensitivity syndrome. AB - OBJECTIVE: Determine the sequence of the androgen receptor gene in men with impaired responsiveness to androgens in order to identify the molecular basis of their under-virilization. DESIGN: Blood samples were used as the source of genomic DNA. Portions of the androgen receptor gene were amplified by polymerase chain reaction and sequenced. PATIENTS: Samples were obtained from three patients and five normal fertile controls. Patients were all 46 XY and were undervirilized with ambiguous external genitalia, gynaecomastia and infertility. MEASUREMENTS: Total cellular DNA was purified from peripheral blood leucocytes. Pairs of oligonucleotide primers designed to flank the individual exons of the androgen receptor gene were synthesized. The specific regions of the androgen receptor were amplified from the samples of cellular DNA by polymerase chain reaction. Amplified DNA was purified, sequenced and compared to the published sequence. RESULTS: In all three patients point mutations in the androgen receptor gene were detected but no defects were detected in samples from normal controls. In two of the patients, an identical single nucleotide change from G to T was detected. This nucleotide was within the codon for amino acid 866 and would change it from valine to leucine. Amino acid 866 is found within an area of the steroid binding domain thought to be involved in receptor dimerization. Within the repetitive sequence of exon I patient 1 had 21 glutamine residues and patient 2 had 25. In the third patient a single change of G to A would result in incorporation of lysine in place of a conserved arginine residue at position 607 within the second zinc finger of the DNA binding domain. The sequence of the androgen receptor gene of the mother of the third patient revealed her to be heterozygous for the same defect. CONCLUSION: Patients 1 and 2 are unrelated although they have an identical point mutation in their androgen receptor gene. A patient with complete androgen insensitivity syndrome has been reported to have a defect at the same position causing the amino acid substitution of methionine for valine. Therefore we confirm that the nature of the amino acid change in the peptide sequence of the androgen receptor as well as its location within the protein, can have a profound effect on the phenotypic severity of androgen resistance. Studies on mutated receptors from individuals with a wide range of degrees of androgen resistance may enable us to construct a map of the key amino acids in the different domains of the protein. PMID- 1424204 TI - Oestrogen secreting Leydig cell tumour and GnRH agonist in-vivo and in-vitro studies. AB - OBJECTIVE: The purposes of our study concerning two patients with oestrogen secreting Leydig cell tumour were to determine whether endogenous LH levels are involved in testicular tumour steroidogenesis and whether aromatase activity of oestrogen secreting Leydig cell tumours is directly or indirectly dependent on LH levels. MEASUREMENTS: E2 and T were evaluated after hCG injection (5000 IU) during 96 hours. Bio and immuno LH, T, E2, were determined at the basal state and after administration of D-Trp-6-GnRH agonist (3.75 mg) every 3 weeks. The abnormal testis was removed after the third injection and testicular venous blood was collected during the operation. Testicular tumour was incubated with 4-14C-T. RESULTS: Oestradiol (E2) response to hCG injection (5000 IU) was prolonged and exaggerated while that of testosterone (T) was similar to that of the controls. The aromatase index (E2/T) remained elevated even 96 hours after hCG. Intramuscular injection of the GnRH agonist, D-Trp-6-GnRH (3.75 mg) resulted in a reduction of immunoreactive and bioactive LH. T was decreased to about 10% of baseline levels and E2 fell from 240 to 36 pmol/l. In the blood of the spermatic veins collected in the course of surgery, E2 levels were found to be lower in comparison with the controls. E2 was found to be twofold higher in the spermatic vein draining the tumoral side than in that of the contralateral testis. Incubation of the testicular tumours with 4-14C-T, displayed a reduced aromatase activity (conversion of T to E2: 0.3 and 0.1% in patients 1 and 2 respectively). CONCLUSIONS: The kinetics of E2 response to hCG administration would suggest a modification of the regulation of the aromatase activity in this type of oestrogen secreting tumour. A certain endogenous LH level may be necessary to supply a sufficient quantity of T substrate, and to maintain aromatase activity of such Leydig cell tumours secreting oestrogens. These tumours seem to be responsive to endogenous LH levels. PMID- 1424205 TI - Prevalence of gastritis in patients with acromegaly: untreated and during treatment with octreotide. AB - OBJECTIVE: It has previously been suggested that acromegalic patients treated with the somatostatin analogue octreotide invariably have chronic gastritis. We have examined the prevalence of gastritis in a large group of acromegalic patients, untreated and during treatment with octreotide. DESIGN: We studied three groups of acromegalic patients: (A) untreated; (B) octreotide-treated; (C) a subgroup of these studied both before and during octreotide therapy. PATIENTS: Forty-eight patients, grouped as above, with active acromegaly were examined for the presence of gastritis. MEASUREMENTS: Gastroscopy and histological examination of gastric biopsies for the presence of gastritis and Helicobacter organisms were undertaken. The principal outcome was quantification of the prevalence of gastritis in the various study groups. RESULTS: Group A: 10 of the 33 patients (30%) had gastritis before any therapy with octreotide. Group B: 17 of 36 patients (47%) on octreotide treatment for 6-59 months (mean 20.5) had gastritis, and this was present in five out of the sub-group of eight patients (62%) treated for over 3 years. Group C: three of 21 patients (14%) developed gastritis during treatment with octreotide for between 6 and 23 months (mean 12.4). There was a highly significant association between the presence of gastritis and the presence of Helicobacter pylori organisms. CONCLUSIONS: Octreotide therapy of acromegaly may predispose to the development of gastritis, but this remains statistically unproven. Certainly, gastritis is not an invariable consequence of octreotide therapy, even after prolonged periods of treatment. The presence of gastritis is associated with H. pylori infection. PMID- 1424206 TI - Long-term in-vitro treatment of human growth hormone (GH)-secreting pituitary adenoma cells with octreotide causes accumulation of intracellular GH and GH mRNA levels. AB - OBJECTIVE: We studied the effects of long-term in-vitro exposure of human GH secreting pituitary adenoma cells to octreotide on GH release, intracellular GH concentrations and GH messenger ribonucleic acid (mRNA) levels. DESIGN: Human GH secreting pituitary adenoma cells were cultured for periods from 4 days up to 3 weeks without or with octreotide (10 nM) and/or bromocriptine (10 nM). The effects of these drugs were measured on GH release, intracellular GH concentrations and intracellular GH mRNA levels. PATIENTS: Thirteen patients with GH-secreting pituitary adenomas were studied. Twelve patients were untreated, one had been pretreated with octreotide (12 weeks, 3 x 100 micrograms daily). MEASUREMENTS: GH, PRL, alpha-subunit and IGF-I concentrations in plasma, media and cell extracts were determined by immunoradiometric or radioimmuno-assays. GH mRNA levels were determined by automatic quantification of grain numbers in individual adenoma cells. RESULTS: Incubation of the adenoma cells for 4 days with 10 nM octreotide induced a dose-dependent inhibition of GH release and a parallel increase (increase varying between 124 and 617% of control) in the intracellular GH levels was observed in six of seven adenomas. In addition, bromocriptine, when effective in inhibiting GH release by the adenomas, also induced an increase in intracellular GH levels. Even after 3 weeks of exposure to 10 nM octreotide in vitro there was a statistically significant increase in intracellular GH levels (between 191 and 923% of control). Withdrawal of octreotide after 6 days of incubation resulted in a lowering of intracellular GH levels to control values, showing that the octreotide-induced increase in intracellular GH is reversible. In a 96-hour incubation with 10 nM octreotide, GH mRNA levels were increased in two, and slightly decreased in one of the three adenomas tested. This effect was time dependent in that there was no significant effect of 10 nM octreotide on GH mRNA levels in a 24-hour incubation. CONCLUSIONS: (1) Long-term in-vitro exposure of GH-adenoma cells to octreotide causes an increase in intracellular GH levels in the majority of the adenomas, probably because of an increase in GH mRNA levels in the adenoma cells; and (2) this considerable increase in intracellular GH levels may be one of the explanations for the relatively poor effect of octreotide on tumour shrinkage in patients with GH-secreting pituitary adenomas. PMID- 1424207 TI - Effect of growth hormone on the low level of growth hormone binding protein in idiopathic short stature. AB - OBJECTIVE: Growth hormone receptor status was assessed in children with idiopathic short stature by evaluating plasma growth hormone-binding protein before and under GH therapy. DESIGN: Among 22 children presenting idiopathic short stature, 15 were randomly selected to be treated with GH (1.2 IU/kg/week); they were studied before and under GH therapy. Untreated patients served as a control group for age and GH effect. PATIENTS: Twenty-two prepubertal children, aged 5-11 years, were studied. They presented growth retardation of -2.8 +/- 0.1 SDS (mean +/- SEM). All had normal GH secretion and their mean IGF-I plasma level was normal. MEASUREMENT: Growth hormone-binding protein was measured using high pressure liquid chromatography gel filtration. The specific binding of 125I-hGH to the growth hormone-binding protein was expressed as a percentage of the total radioactivity. RESULTS: Specific binding of 125I-hGH to the high affinity growth hormone-binding protein was low with a mean +/- SEM value of 11.1 +/- 0.9% of radioactivity. In the treated group, growth hormone-binding protein increased significantly after 3 months of treatment; it reached 21.1 +/- 1.0% of radioactivity (mean +/- SEM) in the eight children who have been treated for 18 months. In the seven untreated children, the growth hormone-binding protein value increased to 16.2 +/- 1.1% after 18 months; this value is significantly lower than that found in the GH-treated children, demonstrating that the GH effect is greater than the age-related increase in the growth hormone-binding protein. A positive correlation was found between IGF-I plasma levels and growth hormone binding protein and also between growth velocity and growth hormone-binding protein. CONCLUSIONS: The low growth hormone-binding protein and the response to high doses of GH suggest partial GH resistance at the receptor level, in this group of children with idiopathic short stature. PMID- 1424208 TI - Pituitary histology in Cushing's disease. AB - OBJECTIVE: We assessed pituitary histology in patients with Cushing's disease. DESIGN: Systematic histological assessment of pituitary tissue removed at surgery. PATIENTS: Thirty-six consecutive patients cured from Cushing's disease by transsphenoidal neurosurgery. MEASUREMENTS: Microscopical examination of all available tissue removed at operation. RESULTS: After selective removal of tissue supposed to represent an adenoma in 25 patients this could be histologically verified in 18. In the 11 patients who had undergone a total hypophysectomy an adenoma could be demonstrated in three patients only, despite a systematic search of the entire pituitary gland. Only in 21 of the 36 cured patients (58%) could an adenoma be verified. CONCLUSIONS: Combining the present results with previous reports there is strong reason to believe that in some patients with Cushing's disease no histological lesion in the pituitary is verifiable. PMID- 1424209 TI - Usefulness of thyroglobulin antibody detected by ultrasensitive enzyme immunoassay: a good parameter for immune surveillance in healthy subjects and for prediction of post-partum thyroid dysfunction. AB - OBJECTIVE: Using newly developed ultrasensitive enzyme immunoassay (EIA) for thyroglobulin antibody (TgAb), we have evaluated physiological and pathological implications of the antibody in healthy subjects as well as in autoimmune thyroid diseases. MEASUREMENTS: This EIA was based on the immune complex transfer method, and was 10(4)-fold more sensitive compared with the conventional haemagglutination assay (HA); the detection limit was 0.1 micrograms IgG/I, and the specificity of the assay was confirmed from the unequivocal decrease in the fluorescence intensity by the preincubation of test serum with Tg and/or inactive beta-D-galactosidase which blocks antibodies to the enzyme. RESULTS: TgAb was detectable in 159 (91%) of 175 healthy subjects aged 3rd to 7th decade (96 men and 79 women), and did not exhibit age or sex-associated change. In nine healthy women, the TgAb level significantly decreased as pregnancy progressed but increased transiently after delivery. TgAb was detectable in 52 (98%) of 53 patients with Graves' disease and all (100%) of 107 patients with chronic thyroiditis. Abnormal high TgAb values (> 40 micrograms/I), determined from the 95th percentile in healthy subjects, were shown in 40 (75%) with the former disease and 94 (88%) with the latter disease. Moreover, in 14 goitrous patients with biopsy-proved chronic thyroiditis with negative HA results, 12 (86%) showed abnormal high TgAb levels. In 69 patients with post-partum thyrotoxicosis in Graves' disease, 15 (79%) of 19 patients with the TgAb level of more than 2 x 10(3) micrograms/I in early pregnancy showed destructive thyrotoxicosis and 46 (92%) of 50 with less than this level showed stimulative thyrotoxicosis. This TgAb test could discriminate the two types of thyrotoxicosis more clearly than could the conventional TGHA test. In chronic thyroiditis, the mean TgAb value in early pregnancy was significantly higher in patients with postpartum hypothyroidism than in those without thyroid dysfunction. Hypothyroidism developed in 80% of the patients with a TgAb value of more than 10(3) micrograms/I. CONCLUSIONS: The ultrasensitive TgAb EIA was useful for detecting the physiological changes in autoantibody formation in healthy subjects and the TgAb value was useful for predicting post-partum thyroid dysfunction in autoimmune thyroid diseases. This EIA is useful for the evaluation of the immune surveillance in patients with autoimmune thyroid diseases as well as in healthy subjects. PMID- 1424210 TI - Thyroid cells in Graves' disease and Hashimoto's thyroiditis stimulate allogeneic T cells when pretreated with phorbol ester. AB - OBJECTIVE: To assess the capacity of thyroid follicular cells to function as antigen presenting cells, we have examined their ability to stimulate allogeneic T cells. DESIGN: Thyroid follicular cells were pretreated with interferon-gamma or phorbol myristate acetate, washed thoroughly, and their capacity to induce allogeneic T cell proliferation was determined. PATIENTS: Thyroid cells were prepared using thyroidectomy specimens from eight patients with Graves' disease, one with Hashimoto's thyroiditis and two with non-toxic multinodular goitre. MEASUREMENTS: T cell 3H-thymidine incorporation was measured after a 16-hour incubation period with the isotope, 3 days after co-culture of T cells and thyroid cells. RESULTS: Four of the eight thyroid cell preparations from thyroid autoimmunity patients failed to stimulate T cells, although there was a significant, weak stimulation for the whole group (P < 0.05): interferon-gamma pretreatment had no effect on this. Phorbol myristate acetate pretreatment significantly increased the ability of thyroid cells (from both autoimmune and multinodular glands) to stimulate T cells (P < 0.05); this was time and concentration dependent. Cell fixation after PMA treatment did not abolish this stimulatory activity, which could be transferred by supernatants from unfixed cells; exogenous interleukin-1 did not mimic the activity. CONCLUSIONS: Thyroid cells expressing major histocompatibility complex class II molecules only weakly and inconsistently stimulate allogeneic T cells, compared to thyroid cells pretreated with phorbol myristate acetate, a difference which may be due to the expression of an unidentified co-stimulatory signal induced by phorbol ester. PMID- 1424211 TI - Treatment of osteoporosis with parathyroid peptide (hPTH 1-34) and oestrogen: increase in volumetric density of iliac cancellous bone may depend on reduced trabecular spacing as well as increased thickness of packets of newly formed bone. AB - OBJECTIVE: We wished to determine whether treatment of vertebral osteoporosis with human parathyroid peptide 1-34 (hPTH 1-34), given as a daily injection with supplementary treatment with hormone replacement therapy (HRT), increases cancellous bone area in the ilium by increasing the size of packets of new bone. DESIGN AND MEASUREMENTS: The width of packets of cancellous bone (wall width) was measured at random intercepts and mean values calculated. Cancellous bone area and perimeter were also measured. Indices of trabecular separation and the complementary quantity trabecular number were derived according to Parfitt's method, as well as trabecular width. Patients were used as their own controls and changes in these indices calculated. Correlations were calculated for data obtained from independent measurements. PATIENTS: We studied eleven women with post-menopausal osteoporosis, diagnosed by fractures after exclusion of causes of secondary osteoporosis. RESULTS: One woman did not comply with her HRT therapy. In the others, treatment with hPTH 1-34 + HRT restored the characteristically depressed pre-treatment values of wall width to normal. Trabecular width increased approximately four times more than wall width. Changes in wall width correlated with changes in cancellous bone area; however, bone area increased considerably more than could be accounted for statistically by changes in wall width. A decrease in trabecular separation was found to account for the additional increase in bone area (P = 0.056). CONCLUSION: hPTH 1-34 + oestrogen and progestagen therapy increases the width of packets of new cancellous bone with consequent increases in the width of trabecular plates. PMID- 1424212 TI - Circulating levels of midregional parathyroid hormone-related protein in hypercalcaemia of malignancy. AB - OBJECTIVE: We have developed and evaluated a sensitive radioimmunoassay directed against the midregional part of parathyroid hormone-related protein (PTHrP), which is involved in the syndrome of humoral hypercalcaemia of malignancy. PATIENTS: Midregional PTHrP levels were studied in 41 consecutive inpatients with malignancy and hypercalcaemia, 32 normocalcaemic patients with malignancy, 21 patients with primary hyperparathyroidism, 34 patients with renal failure, and 87 normals. MEASUREMENTS: The assay used an antiserum against the midregional amino acid residues 53-84 of PTHrP and PTHrP(1-86) as label and standard. Midregional PTHrP was stable in serum and plasma and could be measured directly without sample extraction. RESULTS: Normal plasma concentrations ranged from undetectable (< 5 pmol/l) to 21 pmol/l. In renal failure, PTHrP was positively correlated with serum creatinine, but PTHrP elevations of up to 30 pmol/l were found only in severe renal dysfunction with creatinine > 850 mumol/l. In hypercalcaemia caused by solid tumours, midregional PTHrP was elevated in 81% (22 of 27) of patients, ranging from undetectable to 203 pmol/l (median: 40 pmol/l). In these patients serum calcium correlated positively with PTHrP (P < 0.01). Mean PTHrP levels were indistinguishable in subgroups with and without metastatic skeletal disease. The mechanism of hypercalcaemia in 14 patients with haematological malignancy was apparently different, since all but one had normal or only marginally elevated PTHrP levels. In 21 patients with primary hyperparathyroidism midregional PTHrP was normal in 20. The assay was therefore especially useful in distinguishing the latter condition from humoral hypercalcaemia of malignancy as the second major cause of hypercalcaemia. PTHrP was normal in all 32 patients with normocalcaemic malignancy. CONCLUSION: This radioimmunoassay of midregional PTHrP provides high diagnostic sensitivity in the identification of humoral hypercalcaemia of malignancy caused by solid tumours. The assay should therefore be useful in the differential diagnosis of hypercalcaemia. PMID- 1424213 TI - Post-pregnancy osteoporosis associated with hypercalcaemia. AB - A lactating 31-year-old woman who developed four vertebral fractures 1-2 months after the delivery of her first child is described. She was hypercalcaemic (serum calcium up to 2.99 mmol/l), and urinary excretion of both calcium and hydroxyproline (an index of bone resorption) were markedly elevated. Serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D were suppressed, but parathyroid hormone-related peptide was above normal. There was severe axial osteopenia, as assessed by dual-energy X-ray absorptiometry. The biochemical abnormalities were reversed within 2 weeks of weaning, with the exception of the parathyroid hormone-related peptide concentration, which declined more gradually. This appears to be the first description of the abnormalities in calcium metabolism and bone density from early in the course of post-pregnancy osteoporosis and it indicates that this condition is associated with high levels of osteolysis which return to normal after weaning. This rapid reversal of the metabolic abnormalities accounts for the inconclusive nature of previous descriptions of post-pregnancy osteoporosis, in which investigations were more delayed. It also emphasizes the importance of weaning in the management of women presenting with this condition. A possible aetiological role for parathyroid hormone-related peptide is discussed. PMID- 1424214 TI - Phaeochromocytomas as a cause of hypotension. AB - A patient presented with apparent septicaemic shock. Full invasive cardiovascular monitoring revealed systemic hypotension, high normal cardiac output, and a low systemic vascular resistance. Maintenance of systemic vascular resistance and blood pressure was shown to be highly dependent on noradrenaline. Subsequent investigation revealed the presence of a phaeochromocytoma producing adrenaline. The mechanisms by which phaeochromocytomas may produce hypotension are discussed. PMID- 1424215 TI - Effects on renal function and digoxin-like immunoreactivity produced by methimazole in low-renal mass hypertension. AB - This study evaluates the effects of methimazole, an antithyroid drug, on blood pressure, digoxin-like immunoreactive factor (DLIF) production and other variables related to salt and water metabolism in low-renal mass (LRM) hypertension. Drinking administration of methimazole (0.025%) from replacement of water by the 1% NaCl solution maintained the blood pressure of low-renal mass rats at normal levels during four weeks after hypertension induction. Serum and urinary excretion of DLIF were significantly increased in LRM rats with respect to controls; in all tests, the highest values of DLIF were found in LRM methimazole treated (LRM-M) rats. Urinary excretion of DLIF showed positive correlations with diuresis and natriuresis in all three groups (control, LRM and LRM-M rats). However, the correlation between DLIF and sodium disappeared when both factors were expressed as a function of their concentrations. These results indicate that methimazole prevents LRM hypertension and suggest that DLIF might not represent the putative natriuretic hormone. Other findings were that methimazole-treatment reduced renal compensatory hypertrophy subsequent to subtotal nephrectomy, and did not modify the characteristic polyuria-polydypsia in this type of hypertension. PMID- 1424217 TI - Definitions and characteristics of salt-sensitivity and resistance of blood pressure: should the diagnosis depend on diastolic blood pressure? AB - To elucidate the importance of diastolic blood pressure in the definition of salt sensitive hypertension, we studied 54 male subjects, 36 of whom had untreated, mild essential hypertension. The subjects received a 120 mmol/d Na (as the chloride salt) diet for six days. Thereafter they received a 10 mmol/d Na diet for eight days followed by a 400 mmol/d Na diet for another 8 days. Blood pressure was measured hourly "around the clock" on the last day of each diet; the averaged systolic, diastolic and mean blood pressure values were compared. In 22 subjects diastolic blood pressure increased, when salt intake was increased from 10 to 400 mmol/d. In 18 of these 22 subjects systolic blood pressure increased as well. In 20 subjects, systolic blood pressure increased with salt loading while diastolic blood pressure decreased. In 13 subjects both systolic and diastolic blood pressure decreased with increased salt intake. We defined those subjects showing an increase in diastolic blood pressure as salt-sensitive. If mean blood pressure were used to define salt-sensitivity, 8 of our subjects would have been labeled as salt-sensitive who actually decreased their diastolic blood pressure with salt loading. We suggest that consideration of systolic and diastolic blood pressure responses gives better insight into identifying volume and resistance related phenomena in salt-sensitive hypertension, than does the consideration of mean blood pressure alone. The definition of salt-sensitivity may require reassessment. PMID- 1424216 TI - Calcium suppresses central angiotensin II pressor response less in SHR. AB - To determine whether calcium alters central cardiovascular regulation, cardiovascular responses to intracerebroventricular (ICV) injection of calcium were recorded in conscious Wistar rats. Calcium injection consistently produced dose-dependent decreases in mean parterial pressure and heart rate. Pretreatment with a calcium channel blocker, diltiazem, attenuated cardiovascular responses to calcium. Decreases in plasma norepinephrine indicated the contribution of sympatho-inhibition to vasodepression by calcium. Preceding calcium injection reduced pressor responses to ICV-injected angiotensin II. These findings suggest that there is a pharmacological interaction between calcium and angiotensin II in the central nervous system. In spontaneously hypertensive rats (SHR), cardiovascular responses to calcium was larger than Wistar Kyoto rats (WKY). By contrast, calcium reduced pressor responses to angiotensin II only in WKY but not in SHR. Because the central interaction between calcium and angiotensin II has been different in SHR, our results imply that this difference may be related to the maintenance of high blood pressure in SHR. PMID- 1424218 TI - Cardiovascular responses to centrally applied sodium chloride solution. AB - In conscious and anaesthetized rats the baroreceptor heart reflex (BHR) was checked before and after i.c.v. application of isotonic or hypertonic (0.6 M; 1.0 M) NaCl solution, artificial cerebrospinal fluid (aCSF) and 1.0 M mannitol solution. The BHR was tested by evaluating the alteration of the inter-beat interval (IBI) in response to an artificial BP rise or drop which had been evoked by i.v. bolus injection of either phenylephrine or sodium nitroprusside. The slope of the correlation function was taken to index the reflex sensitivity. In anaesthetized rats the mean sensitivity of the BHR was 0.6 ms/mm Hg (phenylephrine). l.c.v. administration of isotonic NaCl solution did not change BP, IBI or the BHR sensitivity, whilst i.c.v. infusion of hypertonic NaCl solution increased BP and shortened IBI. The BHR sensitivity was impaired only when 1.0 M NaCl solution was i.c.v. infused by 0.23 ms/mm Hg. In conscious rats the mean sensitivity of the BHR was 1.14 ms/mm Hg (phenylephrine) and 1.35 ms/mm Hg (sodium nitroprusside). In the conscious rats i.c.v. bolus injection of hypertonic NaCl solution increased BP as in anaesthetized rats, however, the IBI was prolonged, whilst 1.0 M mannitol solution and aCSF were without any influence on BP, IBI and BHR. l.c.v. administration of hypertonic NaCl solution reduced the BHR sensitivity by approximately 0.6 ms/mm Hg. PMID- 1424219 TI - White blood cell and lymphocyte populations following interleukin-2 administration in the spontaneously hypertensive rat. AB - The immune system has been linked to the pathogenesis of hypertension in the spontaneously hypertensive rat (SHR). Recently interleukin-2 has been reported to inhibit the development of hypertension in the SHR, but no measures of different lymphocyte populations were made. To test the effect of interleukin-2 we repeated the protocol in the report by injecting forty two day old, male SHR and WKY rats, and in addition, analyzed lymphocyte subpopulations. Untreated, age matched rats of the same strain were used as a control. At three and four months of age blood was drawn from all animals. Monoclonal antibodies were used to fluorescently label different lymphocyte subpopulations. The populations examined were the total T-cells, T-nonhelper cells, T-helper cells and B-cells. Total numbers of lymphocytes and white blood cells were also examined. Blood pressures were measured in conscious, restrained animals at two and four months of age. The results showed no attenuation of blood pressure in the interleukin-2 treated SHR at either age. The interleukin-2 treated SHR had a decrease in the percentage of B-cells and an increase in the percentage of T-nonhelper cells relative to the control SHR. Both treated and untreated SHR had increased numbers of white blood cells and lymphocytes compared to both groups of WKY. We conclude that the interleukin-2 used was active but failed to have any effect on blood pressure or absolute numbers of white blood cells and lymphocytes in the treated animals. PMID- 1424220 TI - Relaxation of non-contracted smooth muscle by atrial natriuretic peptide. AB - Atrial natriuretic peptide (alpha-hANP-99-126), 1 x 10(-8) to 5 x 10(-10) M was able to further relax the non-contracted aortic smooth muscle of rabbit after complete recovery from a previous challenge with human angiotensin II (AII), 1 x 10(-6) M. The relaxation was directly proportional to the response of the ring or strip to the previous challenge with AII. ANP does not have effect on basal tension in isolated strips or rings of the rabbit aorta not previously exposed to AII. Norepinephrine (NE), 10(-7) M was less potent in inducing reactivity of the vessel to ANP, ie, only a small relaxant effect on basal tension could be observed. A similar vasorelaxant effect of ANP on basal tension could be obtained in the absence of extracellular calcium: Ca(2+)-free Ringers' solution containing 2 mM ethylene-glycol-bis (beta-aminoethyl ether)N',N' tetraacetic acid (EGTA Ringer). In contrast, sodium nitroprusside 10(-8) M does not affect basal tension. Present results demonstrate the role of the physiological state of the vessel in the reactivity to ANP. PMID- 1424221 TI - Circadian blood pressure variation in patients with renovascular hypertension or primary aldosteronism. AB - Circadian blood pressure (BP) variation were studied in patients with renovascular hypertension (RVH) and primary aldosteronism (PA). Ambulatory BP (ABP) was monitored every 5 min for 24 hrs in a ward setting in 23 patients with PA and 17 patients with RVH (13 patients with unilateral renal arterial stenosis and 4 with bilateral stenosis). In patients with RVH, ABP was monitored before and after treatment with a converting enzyme inhibitor or percutaneous transluminal angioplasty. Plasma renin activity (PRA) was high before percutaneous transluminal angioplasty in almost all patients with RVH and low in those with PA. Ordinary circadian BP variation, i.e. nocturnal fall and diurnal rise in BP, was confirmed in the patients with unilateral or bilateral renal artery stenosis. Percutaneous transluminal angioplasty successfully normalized both BP and PRA in those with RVH. Normal circadian BP variation was observed in those with RVH before the treatment with a converting enzyme inhibitor or percutaneous transluminal angioplasty as well as during treatment with the former and after treatment with the latter. Circadian BP variation in the patients with RVH was affected by the pathogenesis of renal artery stenosis alone, i.e, fibromuscular hyperplasia and atherosclerosis; with fibromuscular hyperplasia normal circadian BP variation was observed, while with atherosclerosis, nocturnal BP fall was restricted or eliminated. Circadian BP variation in those with PA before and after excision of adrenal adenoma was essentially similar to that in normal subjects and essential hypertensive patients. From these it seems that in patients with RVH or PA, circadian BP variation is not affected by hypertension per se or by pathogenesis of hypertension. PMID- 1424222 TI - Stimulation of renal dopamine production during acute volume expansion requires the presence of intact vagi but not renal nerves. AB - We have previously reported that acute volume expansion (VE) with isotonic saline stimulates the production of renal dopamine (DA) which in turn contributes to the accompanying diuresis and natriuresis via activation of renal tubular DA-1 receptors. The purpose of the present study was to determine whether the presence of vagi and/or renal nerves is essential in order to activate the renal dopaminergic system during acute VE. Acute VE (6% body weight) with isotonic saline was performed in two groups of anesthetized rats, one of which served as sham control whereas the other was subjected to bilateral cervical vagotomy. The diuretic and natriuretic responses to acute VE did not differ between the sham control and vagotomized groups. However, urinary DA excretion (UDAV) was significantly increased in the sham control but not vagotomized group. Pretreatment with SCH 23390, a selective DA-1 receptor antagonist led to significant attenuation of the diuretic and natriuretic response to acute VE in the sham control but not vagotomized group. In another group of animals, the diuretic and natriuretic response to acute VE was studied in rats subjected to acute unilateral renal denervation. Basal UDAV was not significantly different between the denervated (DNX) kidney and the contralateral innervated (INX) kidney. Acute VE evoked diuresis and natriuresis in both kidneys, the response in the DNX kidney being significantly greater when compared to that in the INX kidney. UDAV increased significantly and to similar levels in both kidneys. Pretreatment with SCH 23390 led to attenuation of the diuretic and natriuretic response to acute VE in the DNX but not INX kidney. After DA-1 receptor blockade, the residual renal response to volume expansion in the DNX kidney did not differ significantly from that in the INX kidney. The results of this study suggest that 1) afferent vagal pathways appear to mediate the VE induced stimulation of renal DA production; 2) the increase in UDAV during acute VE occurs primarily through a mechanism which is independent of renal noradrenergic and putative dopaminergic nerves. PMID- 1424224 TI - Efficacy and safety of felodipine, a new dihydropyridine calcium channel blocker, in elderly hypertensive patients. AB - Felodipine is a new dihydropyridine calcium channel blocker with a number of properties that enhance its suitability as a first-line antihypertensive drug for the elderly. Felodipine has a 100-fold selectivity for inhibiting the contribution of vascular smooth muscle compared with cardiac muscle. Negative inotropic action appears minimal while selectivity appears to increase with age. Felodipine has a minimal effect on smooth muscle of venous capacitance vessels, thereby greatly reducing the likelihood of orthostatic hypotension. Renal effects are favorable; the glomerular filtration rate is increased in some patients. The extended-release formulation of felodipine produces a smooth 24-hour plasma concentration curve and is effective when prescribed once daily. Felodipine appears to lower blood pressure effectively in the elderly patient with few, generally mild, adverse effects. PMID- 1424223 TI - Intracellular Mg2+, Ca2+, Na2+ and K+ in platelets and erythrocytes of essential hypertension patients: relation to blood pressure. AB - Alterations in intracellular cation metabolism have been implicated in the pathophysiology of essential hypertension. Total magnesium, calcium, sodium and potassium levels were studied in serum erythrocytes and platelets, from 154 subjects (76 hypertensive and 78 normotensives; 104 blacks and 50 whites). In the combined black and white hypertensive group, platelet sodium and calcium and erythrocyte calcium were elevated and serum potassium, serum magnesium and platelet magnesium decreased. In the black hypertensive patients, platelet sodium and calcium and erythrocyte calcium were increased, whereas serum magnesium, serum potassium, platelet magnesium and erythrocyte magnesium were decreased. In the white hypertensive group, platelet sodium and erythrocyte calcium were raised and platelet magnesium was decreased. In the black hypertensive patients, serum and platelet magnesium and serum calcium were negatively and erythrocyte and platelet calcium positively correlated with mean arterial pressure. In the white hypertensive patients platelet sodium was directly related to mean arterial pressure. These results suggest that intracellular sodium and calcium overload and magnesium depletion may be important in the pathophysiology of hypertension. Magnesium disturbances are more consistent and widespread in black hypertensive patients than in white hypertensive patients. PMID- 1424225 TI - Age-related decrease of neurogenic release of calcitonin gene-related peptide from perivascular nerves in spontaneously hypertensive rats. AB - Changes in the neurogenic release of calcitonin gene-related peptide (CGRP) by perivascular nerve stimulation (PNS) were investigated in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). CGRP-like immunoreactivity (CGRP-LI) in the perfusate was examined by radioimmunoassay (RIA) and identified to be CGRP itself by combined analysis with radioimmunoassay and HPLC. In SHR and WKY preparations, PNS (4 and 8 Hz) evoked a frequency-dependent increase of CGRP-LI in the perfusate, which was abolished by 500 nM tetrodotoxin and the removal of Ca2+ from the medium. In young SHR and WKY (8-week-old), there was no significant difference in the release of CGRP-LI induced by PNS, whereas the release in the 15-week-old SHR was significantly less than in the 15-week-old WKY and in 8-week old SHR. These results suggest that neural release of CGRP from perivascular nerves in mesenteric resistance vessels of SHR decreases with age. PMID- 1424226 TI - Intestinal failure--the clinical problem. AB - Intestinal failure can be the end result of a wide variety of disease processes that impair the ability of the gut to adequately digest and absorb food. Patients with established intestinal failure may require parenteral nutrition support and/or abdominal surgery to reverse the disease process involved. Selected patients with irreversible intestinal failure can be managed in experienced units by home parenteral nutrition. PMID- 1424227 TI - Small bowel transplantation: past, present and future. AB - As techniques for immune suppression improve, the clinical utility of small bowel transplantation will increase. Recent reports of long-term (over 1 year) survival with totally enteral nutrition following bowel transplantation have increased interest in this area and prompted the present review of the state of the art of small bowel transplantation. Background methodology is emphasized, in order to allow for more critical review of reported models, and to provide a framework for comparing results. The functional capacity of bowel following transplantation, and the effects of immune suppression on bowel function are reviewed in detail. Prospects for future direction in basic and clinical research are discussed. PMID- 1424228 TI - Joint manifestations in gastrointestinal diseases. 1. Pathophysiological aspects, ulcerative colitis and Crohn's disease. AB - The many unique structural and functional features of the intestine may offer explanations to the well-established association between arthritis and inflammatory bowel diseases (IBD). In ulcerative colitis (UC) and Crohn's disease (CD) some 6-8% of cases develop peripheral joint disease which frequently correlates with the activity and extent of the underlying bowel disorder. Ankylosing spondylitis is also found rather frequently in UC and CD, but is apparently not related to the severity of colitis. The occurrence of rheumatic manifestations in these two IBD is reviewed in detail. PMID- 1424229 TI - Structural abnormalities of the Y-chromosome and craniosynostosis. PMID- 1424230 TI - EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) is on 7p11.2-q21.3. PMID- 1424231 TI - MASA syndrome. PMID- 1424232 TI - Association of haptoglobin types with serum lipids and apolipoproteins in a Chinese population. AB - Association of haptoglobin types with serum lipids and apolipoprotein levels was investigated in a healthy Chinese population of both sexes (n = 679) in Singapore. The frequency of Hp1 and Hp2 was found to be 0.30 and 0.70, respectively. The distribution of haptoglobin phenotypes was at Hardy-Weinberg equilibrium in this population. There was an excess of Hp2 in individuals with the upper two quartiles of serum total cholesterol levels compared to those with the lower two quartiles in both sexes (X1(2): 11.84; P less than 0.001). Subjects with Hp 2-2 had significantly higher serum total and LDL cholesterol levels (243.8 +/- 2.83 and 165.9 +/- 2.48 mg/dl) compared to those in other haptoglobin types (230.7 +/- 2.58 and 154.9 +/- 2.49 mg/dl), respectively (P less than 0.001 and 0.002) after adjustments for age, sex and BMI. No other lipid (HDL cholesterol and triglyceride) and apolipoprotein (apo A-I, A-II and B) traits were associated with haptoglobin types. ANOVA statistics using age, sex and BMI as covariates showed that 1.8% of total variability of serum total cholesterol and 2.1% of serum LDL cholesterol could be explained by haptoglobin types (P 0.008 and 0.003, respectively). It is concluded that haptoglobin polymorphism is significantly associated with serum total and LDL cholesterol levels in this Chinese population. PMID- 1424233 TI - A novel truncated apolipoprotein B (apo B55) in a patient with familial hypobetalipoproteinemia and atypical retinitis pigmentosa. AB - We have identified an apolipoprotein (apo) B mutation in a patient with an atypical form of retinitis pigmentosa (RP). In the family the eye disease is characterised by late age of onset and autosomal dominant inheritance. In addition to RP, the proband has low total cholesterol (4.5 mmol/l) and LDL cholesterol (2.0 mmol/l) levels characteristic of the autosomal codominant apolipoprotein (apo) B deficiency disease hypobetalipoproteinemia (HBL). Using a monoclonal antibody directly against apo B and immunoblots of SDS polyacrylamide gel separated plasma, a normal apo B100 and a truncated apo B species with an estimated size of apo B54 was identified in the proband and his RP-affected sister. The location of the mutation in the apo B gene was identified using chemical cleavage of mismatch and this was confirmed by direct sequencing of an amplified fragment of DNA spanning the estimated site of the mutation. The mutation is a C----T transition at nucleotide 7692 which changes the CGA arginine2495 codon to a STOP codon resulting in the premature termination of apo B100. The truncated apo B protein is 2494 amino acids long with a predicted size of apo B55. Using allele specific oligonucleotides and oligonucleotide melting techniques, the proband, his sister and two other relatives out of a total of 20 family members, screened for the presence of the apo B55 mutation, were heterozygous for the mutation. The segregation of the apo B55 allele was confirmed in the family using the 3' variable number of tandem repeats of the apo B gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424234 TI - Ring Y chromosome: cytogenetic and molecular characterization. AB - A female patient with Turner syndrome and the karyotype mos45,X/46,X,r(Y)/46,XY is described. Physical mapping of the ring chromosome by Y-specific single-copy and moderately repeated DNA sequences as molecular probes showed that, in addition to the heterochromatic part of Yq, a considerable portion of the Yp has also been lost in the course of the rearrangement. Thus, molecular findings provide independent support that this structurally abnormal sex chromosome is a ring Y and agree with the generally accepted model of ring formation requiring breaks in both chromosome arms. Clinical consequences of Y chromosome mosaicism in patients with Turner syndrome are discussed. PMID- 1424235 TI - Y-derived sequence detected in minute chromosomes by polymerase chain reaction and in situ hybridization. AB - A 10-year-old girl and a 10-month-old girl, both with ambiguous genitalia, were found to have 45,X/46,X,mar and 45,X/46,X,r(?) mosaicism. The marker chromosomes in both girls were very small. Polymerase chain reaction, with synthetic oligonucleotide primers from Y-specific DNA sequences pY-80 and pY53.3 containing the sex-determining region Y(SRY), proved the marker chromosomes to contain the Y short arm material. In situ hybridization with probe pY-80 confirmed that the marker chromosomes included the Y short arms. These findings, together with ambiguous genitalia in the girls, indicate that the marker chromosomes include the testis-determining factor gene. PMID- 1424236 TI - A study of ten small supernumerary (marker) chromosomes identified by fluorescence in situ hybridization (FISH). AB - In seven cases additional minute chromosomes studied by FISH were identified as no. 3, 11, 15, 18, 21 and X. Findings were unexpected except for partial trisomy 21 in an adolescent with minor features of Down's syndrome. Moreover, an i(18p) in a mentally retarded dysmorphic child and an idic(15) in a child with Fallot tetralogy was confirmed. In a child with r(21), a supernumerary marker was shown to be derived from no. 21, while in the mother an additional marker idic(22) was noted. PMID- 1424237 TI - Typical and partial cat eye syndrome: identification of the marker chromosome by FISH. AB - Three children are reported with typical cat eye syndrome (CES) and three more children with partial CES because of absence of coloboma, in which the supernumerary marker chromosome was studied by FISH. Using a genomic library, and also a centromeric and particularly a cosmid probe of 22q11, partial tetrasomy was shown in all cases. PMID- 1424238 TI - Occipital scalp defect associated with valvular pulmonary stenosis. A new entity? AB - We present a 6-month-old, developmentally retarded male with a congenital scalp defect and associated valvular pulmonary stenosis. Review of the literature revealed one other report on a newborn with the same apparently unique association. PMID- 1424239 TI - The Charcot-Marie-Tooth syndrome: perceptions of disability and projected use of DNA diagnostic tests. AB - The Charcot-Marie-Tooth group of disorders cause significant morbidity in a proportion of the individuals affected. We have shown that there is a significant correlation between the objective neurological assessment of their dysfunction and the individual's subjective perception of their disability. We have also documented the observation that individuals expressing an intention to use prenatal DNA diagnostic services and terminate an "affected" fetus are more severely affected by their disorder than those who would not, or who were unsure about their use of molecular genetic testing. PMID- 1424240 TI - Ring chromosome 22 and neurofibromatosis. AB - Variable constitutional mosaicism, mos45,XY,-22/46,XY,-22,+mar/46,XY, 22,+r(22)/47,XY,-22,+r(22)+mar/ 47, XY,-22,+r(22)*2, was found in PHA-stimulated peripheral blood, in a lymphoblastoid cell line and in cultured skin fibroblasts from a mentally retarded patient with neurofibromatosis. Both the ring chromosome and the small extra marker chromosome stained positively by in situ hybridization with a chromosome 14/22-specific alphoid repeat probe. DNA dosage analysis showed constitutional loss of one copy of the arylsulfatase A gene (ARSA), consistent with its terminal location on 22q. There was no evidence of constitutional loss of D22S1 or D22S28 which flank the neurofibromatosis type 2 (NF2) locus. Analysis of two DNA samples from a skin neurofibroma indicated retainment of two copies of D22S1, whereas the results were ambiguous with respect to tumor-specific loss of one copy of D22S28. It is suggested that the development of neurofibromatosis of unclear type in two r(22) carriers might be associated with somatic mutation of the NF2 locus due to instability of the ring chromosome(s), and in analogy, that somatic mutation of either NF1 or NF2 may account for some cases of neurofibromatosis which do not meet the criteria of either NF1 or NF2. The occurrence of seminoma in the proband may be fortuitous, but could also be due to the presence of a seminoma-associated locus on chromosome 22. PMID- 1424241 TI - Partial trisomy 8q. Two case reports with maternal translocation and inverted insertion: phenotype analyses and reflections on the risk. AB - Partial trisomy 8qter-->q23 or q24.1 has been reported in 15 literature cases. We add two further case reports here. Patient 1 inherited the derivative (2) of a balanced maternal reciprocal translocation t(2;8)(qter;q2300) after 2:2 disjunction and adjacent-1 segregation, and is trisomic for the segment 8qter- >q2300. Patient 2 inherited a recombinant (8) of a balanced maternal inverted insertion inv ins(8)(q1300;q2300q24.2) and is trisomic for the segment 8q24.2- >q2300. The phenotype of both patients is described and compared to the spectrum of symptoms established from the 15 literature cases. This spectrum contains all features observed with a frequency of > = 50%. Patient 1 had 35% of the features of this spectrum; Patient 2 had 47%. The intrauterine survival probability of unbalanced offspring is assumed to be the same in both cases, as nearly the same segments are trisomic. The pedigrees indicate that the inversion carrier may have a reduced production probability of unbalanced gametes and therefore a reduced risk compared to the translocation carrier. PMID- 1424242 TI - DNA probe technology: implications for service planning in Britain. AB - For certain genetic conditions DNA testing identifies carriers and determines the risk status of foetuses, thus helping parents to make more informed prenatal decisions. Data, collected from three genetic centres in England and Wales from August 1986 to July 1990, are used to describe trends in demand for DNA testing, the impact of DNA tests on carrier risk assessment, and the use of DNA tests in relation to pregnancy outcome. Altogether the data include 23,388 subjects and 681 pregnancies in 8738 families divided into five cohorts by year of entry and referral. The most frequent gene disorders referred to the genetic centres are currently being tested or will soon be tested. For these disorders the initial high level of activity has declined and may have reached steady state. Demand for DNA services is high for cystic fibrosis and Duchenne muscular dystrophy, intermediate for Huntington's disease, and low for adult polycystic kidney disease, phenylketonuria and tuberous sclerosis. Based on these findings we suggest that demand for DNA tests will be high in serious, untreatable and slow progressing conditions with early onset; intermediate for conditions affecting intellect and neurological integrity with later onset; and low for treatable, late-onset conditions, or those for which there is evidence of heterogeneity, and variable penetrance. It would be helpful to assess the extent to which this view of demand is confirmed when the new disorders being DNA tested are considered and for the pattern of activity of DNA testing for some types of cancer. Since no DNA centre could offer a fully comprehensive testing service, it is recommended that a structure is created to audit overall activity, assist in policy formulation, and influence supraregional service organisation, in order that the spread of DNA services be planned as effectively as possible. This structure would facilitate monitoring of the evolution of contract specifications agreed by commissioners and providers on a regional basis. PMID- 1424243 TI - Digito-reno-cerebral syndrome: confirmation of Eronen syndrome. AB - In 1985, Eronen et al. described a new autosomal recessive syndrome with absence of the distal phalanges of the toes and fingers, renal defect and cerebral anomalies (dilated ventricles or seizures). Two unrelated children affected by this syndrome enable us to accept its autonomy and delineate its nosology. Variability of the expression of the renal and cerebral manifestations is emphasized. PMID- 1424244 TI - Autosomal inheritance of "senile" retinitis pigmentosa. A report of a family with consanguinity. AB - We describe two sisters affected with retinitis pigmentosa of late onset. Night blindness and progressive visual field loss occurred after 50 years of age in both cases. The parents of affected individuals were first cousins and there was no known history of other similar cases in previous generations. Autosomal recessive inheritance is suggested for such senile retinitis pigmentosa. PMID- 1424245 TI - Clinical, cytogenetic and molecular investigations in three patients with Wolf Hirschhorn syndrome. AB - Clinical, cytogenetic and molecular studies were performed in three patients with Wolf-Hirschhorn syndrome (WHS). In all cases the altered chromosome 4 appeared to be the result of a de novo deletion. Cytogenetic investigations located the breakpoint at 4p15.3 and 4p13. With cytogenetic methods it was not possible to decide whether these deletions were terminal or interstitial. DNA methods also failed to define a distal breakpoint within the 4p16.3 region which might have indicated an interstitial deletion. According to the literature, the paternal chromosome 4 is preferentially deleted in most patients with WHS. DNA analysis with polymorphic markers out of the 4p16.3 region revealed that in two of the cases reported here the deleted segment was of paternal and in one case of maternal origin. PMID- 1424246 TI - Aminoacidopathies among institutionalised mentally retarded in Kuwait. PMID- 1424247 TI - Spondylar dysplasia (SD)/brachyolmia (BO), type I: search for qualitative anomalies in glycosaminoglycans (GAG) PMID- 1424248 TI - Prenatal prediction of cystic fibrosis in a mother homozygous for the delta F508 mutation. PMID- 1424249 TI - Practical use of a disability index in the routine management of acne. AB - We describe a brief questionnaire designed to assess the disability caused by acne. The questionnaire adds a patient-orientated dimension to medical records, high-lights patients with unusually high levels of disability, and increases the relevant information on which we base therapeutic decisions. PMID- 1424250 TI - Accumulation of membrane-bound melanosomes occurs in Langerhans cells of patients with the Leopard syndrome. AB - The Langerhans cells in the lentigines of four patients with the Leopard syndrome contained large membrane bound accumulations of melanin granules. Giant melanosomes were only seen in two patients. The patients had no immune-based symptoms relating to their lentigines. The Leopard Syndrome, also known as multiple lentigines syndrome, progressive cardiomyopathic lentiginosis, lentiginosis profusa syndrome and the cardiocutaneous syndrome, refers to an inherited abnormality of the skin, often associated with cardiomyopathy. The aetiology of the condition is so far unknown and the penetrance is variable. Here we describe electron microscopical findings of large accumulations of melanin within Langerhans cells. PMID- 1424251 TI - How to improve the risk-benefit ratio of cyclosporin therapy for psoriasis. AB - CsA therapy for psoriasis is hampered by side-effects. Topical CsA therapy is not effective. Therefore improvement of the risk-benefit ratio must be achieved by improvement of dose-regimens, combination therapy of CsA with another therapy for psoriasis or combination therapy of CsA with a therapy that may influence the pathogenesis of the most serious side-effect(s) of CsA. It seems that only therapies that influence the pathogenesis of CsA-induced acute renal-impairment, like oral fish oil or perhaps thromboxane synthesis inhibitors, may be beneficial. However, further studies are warranted to validate these findings. PMID- 1424252 TI - Lymphocyte adenosine deaminase activity (L-ADA) in leprosy, during and after treatment of reactions. AB - Twenty-five patients with type 1 (lepra) and type 2 (E.N.L.) leprosy reactions were studied for lymphocyte adenosine deaminase activity (L-ADA), during and after treatment of the reactions, using a standard technique, in order to establish its pattern and if possible, its value in assessing the course of reactions. The results were compared with those from 30 control subjects, comprising 10 normal healthy adults, 10 patients with borderline tuberculoid (BT) leprosy, four patients with borderline lepromatous (BL) leprosy and six patients with lepromatous (LL) leprosy. The level of L-ADA in the leprosy controls was higher than that of normal healthy subjects. The L-ADA values in patients with different types of reactions were about 10-fold higher than those obtained from leprosy controls, emphasizing a possible role in assessing reactions in leprosy. However, there was no significant variation in L-ADA levels, either between the various leprosy controls or reaction groups, before and after treatment. PMID- 1424253 TI - Histopathological study of focal dermal hypoplasia (Goltz syndrome). AB - We report a case of focal dermal hypoplasia, or Golz syndrome in a 13-year-old girl. The patient presented with a variety of cutaneous defects, including atrophy-like depressions, striations, a verrucous papilloma, and lipomas. Histopathological examination showed deposits of fat cells or adipose tissue in the dermis, which were subepidermal, mid-dermal, perivascular, or involved the whole dermis. These findings indicate that the adipose tissue in the dermis is a result of dermal dysplasia and not hypoplasia. PMID- 1424254 TI - Effect of platelet-poor plasma from patients with neurofibromatosis on the growth of cultured neurofibroma-derived fibroblast-like cells. AB - The effect of platelet-poor plasma from patients with von Recklinghausen's disease (neurofibromatosis, NF) on the cell growth of cultured neurofibroma derived fibroblast-like cells (NF fibroblast-like cells grown from explant cultures of cutaneous neurofibromas) was examined. Platelet-poor plasma and sera from nine NF patients and nine control individuals were examined. When comparing platelet-poor plasma from patients with NF with control individuals, the former stimulated the proliferation of fibroblast-like cells derived from neurofibromas, not that of normal fibroblasts. PMID- 1424255 TI - Generalized elastosis perforans serpiginosa in Down's syndrome. AB - Elastosis perforans serpiginosa is a rare disorder of epidermal perforation characterized by the extrusion of dermal elastic tissue through the epidermis. Its aetiology is unknown, but there is histological and biochemical evidence of an abnormality of elastic tissue. Three forms of elastosis perforans serpiginosa exist. It may be either idiopathic, iatrogenic, or, in approximately one quarter of cases, associated with certain genetically determined disorders of connective tissue. Cutaneous lesions appear between the ages of 6 and 20 years, and persist for 6 months to 5 years. They may be confined to one anatomic area, or less frequently are disseminated. We review the case of a 28-year-old woman with recent onset of unusually extensive elastosis perforans serpiginosa with co existing Down's syndrome and (secondary) sclerosing cholangitis. PMID- 1424256 TI - Multiple glomus cell tumours--treatment by infra-red coagulation. AB - This report describes the successful use of infra-red coagulation in the treatment of multiple glomus tumours. Glomus cell tumours are usually solitary and an excisional diagnostic biopsy therefore provides effective treatment. Such an approach is, however, impractical in the rarer condition of multiple glomus cell tumours where up to 400 lesions have been described in one patient. We describe a case of multiple glomus cell tumours in which more than 30 tumours were treated quickly and effectively by infra-red coagulation. PMID- 1424257 TI - HIV seropositivity in association with pityriasis lichenoides et varioliformis acuta. AB - We describe a case of PLEVA in an asymptomatic, human immunodeficiency virus (HIV) positive patient. This association has not been previously described. The possible mechanisms involved are discussed. PMID- 1424258 TI - Chronic actinic dermatitis with vitiligo-like depigmentation. AB - This report describes two patients suffering from severe chronic actinic dermatitis. Unusual widespread vitiligo-like depigmentation occurred during the course of the disease. The progression of these lesions was triggered by the chronic actinic dermatitis. Loss of pigment and complete absence of tyrosinase positive melanocytes were found in depigmented skin of both cases. Immunohistological investigation of the inflammatory infiltrate in case 2 revealed a predominance of CD-8 positive cytotoxic/-suppressor lymphocytes. Analysing the adjacent pigmented epidermis of progressive depigmenting lesions a dense exocytosis of CD-8 T-cells was notable. This distribution suggests cytotoxic destruction of melanocytes as the cause for the vitiligo-like depigmentation. PMID- 1424259 TI - Livedo vasculitis: vasculitis or thrombotic vasculopathy? AB - Elevated fibrinopeptide A levels, suggestive of a thrombogenic state, were observed in six patients with livedo vasculitis. Serological studies demonstrated normal complement levels, and circulating immune complexes were not identified by standard assays. Morphological studies showed no evidence of immune complex deposition or a neutrophilic vascular reaction. These results support classification of this disorder as a thrombogenic vasculopathy rather than as a small vessel vasculitis. Further investigations into the thrombotic abnormalities underlying this entity are warranted. PMID- 1424260 TI - Bullous secondary syphilis. AB - An earlier standard syphilology textbook states that 'If vesicles are an essential part of an eruption in an adult, the lesions are not due to secondary syphilis'. However, vesicular and bullous eruptions do occur in congenital syphilis and rare reports of both vesicular and pustular eruptions in adults with secondary syphilis have been published. We describe a patient with a bullous pemphigoid-like eruption and a positive VDRL in whom treatment with a course of procaine penicillin resulted in rapid permanent resolution of the eruption. PMID- 1424261 TI - Sarcoidosis of the tongue. AB - A 43-year-old man with an 8-month history of swelling of the tongue is described. Biopsy of the tongue revealed numerous epithelioid cell granulomata. A positive Kveim test, elevated angiotensin converting enzyme level and bilateral hilar lymphadenopathy confirmed the diagnosis of sarcoidosis. Sarcoidosis presenting in the tongue is extremely rare. PMID- 1424262 TI - Recalcitrant pyoderma gangrenosum--two cases successfully treated with cyclosporin A. AB - The successful use of cyclosporin A (CSA) in organ transplantation is now well established. In recent years its usefulness has extended to the treatment of cutaneous autoimmune disorders, including pyoderma gangrenosum (P.G.). We report two further cases of recalcitrant P.G., both associated with rheumatoid arthritis (R.A.) which responded to low dose CSA. PMID- 1424263 TI - Systemic lupus erythematosus presenting with 'rheumatoid nodules'. AB - A patient with systemic lupus erythematosus who presented with subcutaneous nodules over the flexor aspect of the fingers in association with arthritis and Raynaud's phenomenon is described. Histopathological examination of the nodules showed appearances consistent with rheumatoid nodules. Further investigations revealed leucopenia and circulating anti-nuclear antibody but negative rheumatoid factor. Immunofluorescence studies of normal non-light exposed skin showed the presence of IgM deposits at the dermo-epidermal junction consistent with systemic lupus erythematosus. The nodules almost disappeared following treatment with hydroxychloroquine. Rheumatoid-like nodules have been reported in systemic lupus erythematosus, although rarely. However, the distribution of the nodules and the patient's clinical course differ from the few cases previously reported in the literature. PMID- 1424264 TI - Angiokeratoma corporis diffusum in a patient with normal enzyme activities and Turner's syndrome. AB - A case of angiokeratoma corporis diffusum (ACD) involving the skin of a 26-year old patient with Turner's syndrome presenting with normal physical and mental development is reported. The unusual nature of this association confirms the theory that ACD presenting with skin lesions alone is a rare but specific clinical entity which differs from the hereditary sphingolipidoses like Fabry's disease. PMID- 1424265 TI - Disseminated granuloma annulare as a presentation of acquired immunodeficiency syndrome (AIDS). AB - Localized granuloma annulare is the commonest form of a granulomatous dermatosis characterized by flesh coloured or violaceous papules often arranged in rings. Several rare atypical variants are also reported including disseminated or generalized, subcutaneous and perforating types. There is a predilection for females and a documented association with diabetes mellitus in some cases. Recently it has been suggested that atypical variants of granuloma annulare might be associated with the acquired immunodeficiency syndrome (AIDS). We describe a patient presenting with extensive generalized granuloma annulare in whom an underlying diagnosis of Human Immunodeficiency Virus (HIV) disease was confirmed. PMID- 1424266 TI - Knobbly granuloma annulare (GA) of the fingers of a milkman--a possible relationship to his work. AB - We report a case of an unusual presentation of granuloma annulare involving the fingers of both hands. The configuration and site is probably related to the particular nature of the man's work as a milkman. PMID- 1424267 TI - Onycholysis in a case of atopic eczema treated with PUVA photochemotherapy. AB - Onycholysis following the ingestion of psoralens and subsequent exposure to natural sunlight has been reported on several occasions and was first reported following photochemotherapy in 1978 by Ortonne and Baran from France and in 1979 by Mackie from Scotland. Mackie commented that she hoped to stimulate further reports of onycholysis induced by PUVA photochemotherapy in order to establish whether or not it was a definite complication of such treatment. Since then, there has been a dearth of similar reports. We describe a patient with severe atopic eczema and alopecia totalis who developed onycholysis of all finger nails and a toe nail during PUVA photochemotherapy. PMID- 1424268 TI - Cutaneous manifestation of X-linked genes escaping inactivation. PMID- 1424269 TI - Topical application of 13-cis-retinoic acid in the treatment of chronic plaque psoriasis. AB - Topical retinoids are of potential value in the treatment of psoriasis. The aim of the present study was to find out whether topical application of 13-cis retinoic acid (13-cis-RA) has an antipsoriatic effect. Nine patients participated in the investigation. In each patient, two comparable psoriatic lesions (5 x 5 cm or more) were selected for treatment with either 13-cis-RA in a 0.1% cream base or with the vehicle only (placebo), using a double-blind approach. The investigation was a left-right within-subject comparison. The lesions were recorded for clinical scores 4 weeks before and after the investigation. Punch biopsies were taken from eight patients before and after treatment and examined using immunohistochemical methods to assess epidermal proliferation and keratinization, and to assess inflammation. Thirteen-cis-RA treatment resulted in a mild decrease of scaling and induration. Erythema however increased. No statistically significant difference in biological effects was achieved between 13-cis-RA and placebo treated lesions and no changes in expression of the immunohistochemical markers were seen. PMID- 1424270 TI - A gp120 HIV peptide with high similarity to HLA class II beta chains enhances PPD specific and autoreactive T cell activation. AB - The recent report that anti-gp120 antibodies can be induced by allogeneic stimuli in experimental animals in the absence of HIV, has focused attention on the structural similarities between gp120 and MHC. Here we report that some HIV+ individuals develop antibodies which similarly react with the gp120 HIV sequence (aa 254-263) and with the HLA-DR beta chains (aa 142-151). As these two peptides share a high level of similarity, we have investigated the role of this gp120 region on HLA class II mediated T cell recognition. The synthetic peptide corresponding to the gp120 HIV sequence aa 254-263 has been tested on T cell line (TCL) activation. Both the PPD-specific and the self-HLA reactive TCL proliferation increased in the presence of this peptide. Prepulsing experiments indicate that this enhancing effect carried out by HIV peptide is exerted at the level of antigen presentation. Moreover, the specificity of this interaction is supported by the fact that a MoAb specific for this HIV peptide blocked the autoreactive TCL proliferation, similarly to the inhibition carried out by anticlass II antibody. These data support the hypothesis that the functional homology between the HIV peptide and the HLA beta chain described may be involved in the pathogenesis of AIDS. PMID- 1424271 TI - Increased expression of IgG Fc receptor type I on neutrophils and monocytes from HIV-infected subjects. AB - Interferon-gamma (IFN-gamma) induces de novo expression of IgG Fc receptor type I (FcRI) on neutrophils and significantly raises the level of these receptors on monocytes. Since increased concentrations of IFN-gamma have been observed in sera from patients with HIV infection, FcRI expression might also be increased on these subjects' phagocytes. FcRI expression was assessed by indirect immunofluorescence staining of phagocytes in whole blood from 40 healthy controls and 55 HIV+ subjects, 24 belonging to CDC class III and 31 to CDC class IV; 42 were intravenous drug abusers (IVDA) and 13 were homosexual men. Plasma levels of IFN-gamma were measured using a modified immunoradiometric assay. The mean linear fluorescence intensity, used as a relative measure of receptor expression, was significantly higher on unseparated neutrophils from HIV+ subjects in CDC classes III (P < 0.001) and IV (P < 0.0001) than from controls. Similar changes in FcRI expression were observed on monocytes from HIV+ subjects. While no differences were observed between IVDA and homosexual HIV+ patients, there was a significant association between FcRI expression and the patients' CDC stage, those in class IV having the highest FcRI levels. Plasma IFN-gamma concentrations were significantly higher in HIV+ patients than in controls and a positive correlation with the stages of HIV infection was again observed. FcRI expression was also increased on freshly purified neutrophils from five HIV+ patients in CDC class IV but did not increase further after 18 h incubation with IFN-gamma, a treatment that up-regulated FcRI expression on control neutrophils. These data suggest that: (i) FcRI evaluation may be a sensitive marker for the biological activity of IFN-gamma in vivo; (ii) phagocytes from HIV+ subjects are activated in vivo by IFN-gamma, expressing increased levels of FcRI; (iii) these IFN-gamma-activated cells may play a role in the pathogenesis of AIDS. PMID- 1424272 TI - Natural killer (NK) cell activity during HIV infection: a decrease in NK activity is observed at the clonal level and is not restored after in vitro long-term culture of NK cells. AB - NK cell activity is impaired in HIV-infected patients. The mechanisms behind the altered NK functions are not clear, and conflicting data concerning NK and antibody-dependent cellular cytotoxicity (ADCC) activity have been reported. In order to investigate whether this impairment is also observed at the clonal level and whether it is related to a defect at the target cell binding and/or the post binding level, we evaluated highly purified NK cell lines and cloned NK cells obtained from 22 HIV-infected patients at different stages of disease and compared them with normal controls for their ability to: (i) kill K-562 and U-937 cell lines using a 51Cr release assay; (ii) bind and kill K-562 and U-937 cells at the single cell binding level; (iii) release NK cytotoxic factor (NKCF), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma); (iv) kill anti-IgM preincubated Daudi cell line (ADCC activity). This study with cloned NK cells or NK cell lines from HIV-infected individuals showed: (i) a decrease in their lytic capability against target cell lines; (ii) a low ability to form conjugates with K-562 and U-937 cell lines with respect to controls; (iii) a decreased ability to kill bound target cells; (iv) low levels of released NKCF, TNF-alpha and IFN-gamma after incubation with U-937 cells. Taken together, these findings suggest that the impaired NK cell function during HIV infection is also observed at the clonal level and is related to defects both at the target and post-binding levels. However, the precise mechanisms remain to be determined. The inability to restore normal NK activity after long-term culture in the presence of high levels of recombinant IL-2 is in agreement with the hypothesis of a 'general anergic process' during HIV infection. PMID- 1424274 TI - Immune response to hepatitis B virus surface antigen peptides during HBV infection. AB - Antibody responses of patients with acute (n = 73), fulminant (n = 30) and chronic (n = 51) hepatitis B virus (HBV) infection as well as recovered individuals (n = 7) were studied against three synthetic peptides, Pre-S1 amino acids (aa. 12-32), Pre-S2 amino acids (aa. 120-145), and S amino acids (aa. 124 147) of the envelope region (HBsAg). T cell blastogenic response was investigated in a proportion of the patients (27 acute, nine fulminant, 13 chronic hepatitis and seven recovered individuals) along with seven HBV vaccinated and three normal individuals. The presence of T cell response against S peptide was observed in all the cases (9/9, 100%) during early acute hepatitis. This was suppressed during late stages (8/18, 44%) followed by partial reversal during recovery (5/7, 71%). T cell response and antibodies to Pre-S1 and Pre-S2 peptides were present only in one-third of the patients throughout these periods. The T cell blastogenic response as well as antibody reactivity against these peptides were absent and minimal in chronic hepatitis. Immune response against envelope protein appears to play a major role in acute hepatic injury due to HBV infection and help in virus clearance. PMID- 1424273 TI - Selection of a muramyl peptide based on its lack of activation of nuclear factor kappa B as a potential adjuvant for AIDS vaccines. AB - Activation of the cellular transcription factor nuclear factor-kappa B (NF-kappa B) by cytokines and other immunostimulants has been tightly linked with enhanced replication of human immunodeficiency virus-type 1 (HIV-1) in infected cells. Various immunomodulators are currently being examined in animal and human trials for their suitability as adjuvants in potential vaccines against acquired immunodeficiency syndrome (AIDS). It may prove to be beneficial to select adjuvants that do not induce NF-kappa B activation and particularly if the vaccines are to be aimed at seropositive individuals. We have examined a battery of synthetic immunostimulants of the muramyl peptide family for their ability to activate NF-kappa B in human and mouse cell lines. In this report, we demonstrate selective activation of NF-kappa B in different cell lines and by different muramyl peptides possessing immunostimulatory activities. The mechanism of such activation is apparently via production of reactive oxygen intermediates (ROI) since pretreatment of cells with antioxidants blocked subsequent activation of NF kappa B. However, among all the molecules tested only one lipophilic, non pyrogenic adjuvant active muramyl peptide showed a complete lack of NF-kappa B activation in all cell lines tested. This molecule could well become the adjuvant of choice in future AIDS vaccines. PMID- 1424275 TI - Immunoglobulin allotypes and IgG subclass antibody response to Pseudomonas aeruginosa antigens in chronically infected cystic fibrosis patients. AB - Chronic Pseudomonas aeruginosa lung infection is the leading cause of death in patients with cystic fibrosis (CF). Poor prognosis correlates with a high number of anti-pseudomonas precipitins and with high levels of IgG2 and IgG3 anti pseudomonas antibodies. Reports of several highly significant associations between certain Gm (genetic markers of IgG on human chromosome 14) and Km (k-type light chain determinants on chromosome 2) phenotypes and immune responsiveness to various antigens suggest that allotype-linked immune response genes do exist in man. Furthermore correlation between Gm types and IgG subclass levels has been reported. A group of 143 CF patients were investigated (31 non-infected and 112 chronic infected). The IgG subclass antibodies to three different P. aeruginosa antigens (P. aeruginosa standard antigen (St-Ag), alginate and LPS) were determined. Immunoglobulin allotypes were determined by haemagglutination inhibition. Samples were typed for G1m(1,2,3, and 17), G2m(23), G3m(5,21), and Km(1,3). Statistical analysis of our data demonstrate that IgG3 anti-pseudomonas antibody levels and Gm markers are related. IgG3 antibody levels to all investigated P. aeruginosa antigens are significantly higher in sera homozygous for Gm(3;5), somewhat lower in heterozygous sera, and significantly lower in sera homozygous for Gm(1,2,17;21). We suggest that genetic differences between the patients may explain the present differences in subclass patterns. PMID- 1424276 TI - Cellular immunity in tuberculous pleural effusions: evidence of spontaneous lymphocyte proliferation and antigen-specific accelerated responses to purified protein derivative (PPD). AB - The kinetics of in vitro cellular proliferation against a PPD of Mycobacterium tuberculosis or streptococcal antigen (streptokinase-streptodornase) was evaluated in pleural fluid and peripheral blood mononuclear cells (PBMC) from patients with tuberculous and non-tuberculous pleuritis. The peak proliferative response to PPD by mononuclear cells from pleural fluid occurred earlier (day 3) in 65% of patients with tuberculosis, a finding not seen in non-tuberculous effusions. Spontaneous lymphocyte proliferation of both peripheral blood lymphocytes and pleural effusion lymphocytes was frequently observed, irrespective of etiology. However, 20 of 21 tuberculous patients manifesting spontaneous lymphocyte proliferation had accelerated kinetics of proliferation to PPD, which was antigen-specific. These results suggest that spontaneous lymphocyte proliferation occurs as a response to antigen stimulation at the site of disease, and is not a non-specific response to inflammation. Furthermore, enhanced reactivity against mycobacterial antigen, manifested by accelerated kinetics of proliferation, has diagnostic potential in patients with pleural effusions. PMID- 1424277 TI - The significance of serum soluble IL-2 receptor as a marker for active visceral leishmaniasis in Sicilian patients. AB - Sera from nine Sicilian patients with confirmed visceral leishmaniasis (Leishmania donovani infantum; VL), at the moment of the diagnosis, during the course of the disease and after clinical recovery, were analysed for the concentration of soluble IL-2 receptor (sIL-2R). The results show that sIL-2R is a marker of disease activity, since it is in high concentration at the beginning of infection and returns to the normal range following successful chemotherapy. At the same time of serum analysis for sIL-2R, peripheral blood mononuclear cells (PBMC) of VL patients were stimulated with phytohaemagglutinin (PHA) or antigen and supernatant tested for IL-2 and interferon-gamma (IFN-gamma) production. Data demonstrate that there is an inverse relation between concentration of IL-2 and IFN-gamma in the supernatants and sIL-2R secretion in the sera. PMID- 1424278 TI - Cellular changes in the bronchoalveolar lavage (BAL) of pigs, following immunization by the enteral or respiratory route. AB - Normal young pigs were immunized by the oral or aerogenic route with the viable or inactivated lung-pathogenic bacterium Actinobacillus (Haemophilus) pleuropneumoniae. Three weeks later the cellular composition as well as the lymphocyte subset composition of the bronchoalveolar space were examined by BAL. Lymphocytes in the lavage increased significantly, including CD4+ and CD8+ T cells. After oral immunization a dramatic increase of plasma cells and lymphoid blasts was found. Among immunoglobulin-positive lymphocytes IgG+ cells showed the most pronounced increase. For most lymphocyte subsets there was no difference between viable and inactivated bacteria. Oral immunization with a lung-pathogenic bacterium results in increased numbers of lymphocytes in the bronchoalveolar space and might play a critical role in protection against lower respiratory tract infections. PMID- 1424279 TI - Activation of normal neutrophils by anti-neutrophil cytoplasm antibodies. AB - Anti-neutrophil cytoplasm antibodies (ANCA) are markers of systemic vasculitis for which a pathogenetic role has been postulated. We have examined the effect of these autoantibodies on the function of normal human neutrophils in vitro. In the presence of ANCA positive sera luminol-amplified chemiluminescence was significantly increased compared to the values seen in the presence of normal or anti-double stranded DNA positive sera (P < 0.01). Five of six ANCA positive F(ab)2 preparations also produced significant neutrophil activation as demonstrated by the chemiluminescence response. This response was totally abrogated by the addition of neutrophil cytoplasm extract, containing the ANCA antigen. Addition of inhibitors to the chemiluminescence system demonstrated that the chemiluminescence response was inhibited by azide and salicylhydroxamic acid and reduced by histidine, suggesting that the chemiluminescence response was due to activation of myeloperoxidase, with generation of singlet oxygen. The chemotactic response to f-Met-Leu-Phe, a bacterial chemotactic peptide, was significantly augmented in the presence of ANCA. Chemotaxis to zymosan-activated serum and chemokinesis was not affected. Phagocytosis was also unaffected. We propose that neutrophil activation and modulation of neutrophil migration by ANCA may be of pathogenetic significance in systemic vasculitis. PMID- 1424280 TI - T lymphocyte expression of complement receptor 2 (CR2/CD21): a role in adhesive cell-cell interactions and dysregulation in a patient with systemic lupus erythematosus (SLE). AB - Complement receptor 2 (CR2, CD21), the receptor for both the C3d,g portion of human complement component C3 and the Epstein-Barr virus, has been recently described on peripheral T cells. By using dual stain flow cytometric analysis, we have also observed that a peripheral T lymphocyte subpopulation of normal healthy donors bears CR2 in a range varying from 1.1 to 23.2% (mean 12.6%) of total CD3+ cells. T lymphocytes from nine patients with inactive SLE expressed CR2 in a similar range. Three patients with active SLE were also studied. One of them, having neuropathy and glomerulonephritis, displayed an expansion of the CR2 T cell subpopulation which reached as much as 89% of total CD3+ cells. To examine potential functional roles of T cell CR2, cells from a Jurkat-derived CR2 expressing T cell line were found to bind in vitro to human CR2-, complement coated K562 cell targets in a CR2- and complement-dependent fashion. Based on these studies, we hypothesize that CR2 might act to increase adherence of T cells to nucleated target cells bearing C3d,g, a function which may be relevant to cytotoxicity or other T cell activities requiring cell-cell interaction. PMID- 1424281 TI - In vitro induction of IgG anti-DNA antibody from high density B cells of systemic lupus erythematosus patients by an HLA DR-restricted T cell clone. AB - An HLA-DR restricted T cell clone (26G11) which recognized a lymphoid cell derived autoantigen associated with DR4 molecule was shown to induce not only autologous but also allogenic DR4+ B cells to produce large amounts of antibodies of the IgG and IgM classes. Using the helper activity of this clone, we investigated the mechanism of anti-DNA antibody production in DR-matched patients with systemic lupus erythematosus (SLE). When cultured with 26G11 cells, B cells from DR-matched normal control subjects produced large amounts of IgM anti-DNA antibody, but did not produce IgG anti-DNA antibody which is thought to have a pathological role in SLE. In contrast, B cells from DR-matched patients with active SLE spontaneously produced a fairly large amount of IgG anti-DNA antibody, and the production was augmented by the T cell clone. Little IgG anti-DNA antibody was produced by the B cells of patients with inactive SLE in either the presence or absence of T cell clone. We next fractionated B cells into low density B (LD-B) and high density B (HD-B) cells by centrifugation on discontinuous Percoll density gradients. IgG anti-DNA antibody was spontaneously produced by LD-B cells of active SLE patients but not by those either of inactive SLE patients or normal controls. On the other hand, although IgG anti-DNA antibody was not spontaneously produced by the HD-B cells of both active and inactive SLE patients, it could easily be induced by their culture with the T cell clone. Our results clearly show the existence of IgG anti-DNA antibody producing B cells in the peripheral blood of SLE patients irrespective of their disease activity and suggest that autoreactive T cells may play a pathogenic role in SLE through the induction of autoantibody production. PMID- 1424282 TI - Detection and characterization of immunoconglutinins in patients with systemic lupus erythematosus (SLE): serial analysis in relation to disease course. AB - The levels of IgA, IgG and IgM immunoconglutinins (IK) were assessed in sera from 20 patients with SLE which were followed for 8-month periods. At the time of the exacerbation, IgG IKs were significantly increased to 226 +/- 90 arbitrary units (mean +/- s.e.m.) compared with both the minimum value of 75 +/- 28 in the SLE patients and with 31 +/- 2 in healthy controls (P < 0.05). There was no difference between SLE patients and controls in the levels of IgM and IgA IKs. Most of the SLE patients in this material showed maximal IgG IK levels before exacerbation, but there was no correlation between the clinical disease index and the levels of IgG IK. The specificity of IgG IKs showed a broad diversity for microtitre-fixed C3b, iC3b, C3c and C3dg. The antibodies were of IgG1, IgG3 and in two patients, IgG4 subclass. IgG IKs were correlated to the C3d/C3 ratio which suggested that the IK responses were secondary to C3 activation. In summary, unlike other conditions associated with complement activation where elevated IgM IKs are common, an increase in IgG IK levels was observed. It is possible that this diverging IK response contributes to the pathophysiology of the disease. PMID- 1424283 TI - IgA rheumatoid factor in mucosal fluids and serum of patients with rheumatoid arthritis: immunological aspects and clinical significance. AB - In order to gain insight into the production and clinical significance of IgA rheumatoid factor (IgA-RF) in mucosal fluids of patients with rheumatoid arthritis (RA), we examined tear fluid, saliva and serum from 80 patients with RA. Significant correlations were found between IgA-RF levels in tear fluid and saliva (P = 0.002, r = 0.57), saliva and serum (P < 0.001, r = 0.79), and serum and tear fluid (P < 0.001, r = 0.31). No significant correlations were found between total IgA levels in these fluids. Comparison between circulating and mucosal IgA-RF levels after correction for total IgA, revealed that mucosal IgA RF levels are on average 2.5 times higher than circulating IgA-RF levels. Analysis of IgA-RF specificity showed that lacrimal and salivary IgA-RF reactivity with various IgG subclasses is similar and differs from serum IgA-RF specificity. These results indicate local production of IgA-RF in salivary and lacrimal glands and support the view of a common origin of IgA-RF producing B cells present in mucosal tissues. Mucosal and circulating levels of IgA and IgA RF were not associated with tests that quantify tear fluid production. This indicates that mucosal and circulating levels of IgA and IgA-RF in patients with RA cannot be regarded as markers for the development of secondary Sjogren's syndrome. PMID- 1424284 TI - Suppression of spontaneous murine lupus by inducing graft-versus-host reaction with CD8+ cells. AB - Splenic CD8+ (Lyt-2+) cells of C57BL/6 mice were injected into semiallogeneic (NZB x BXSB)F1 mice, which spontaneously develop lupus nephritis, in order to examine whether the disease was somehow modified by the occurrence of graft versus-host reaction. The development of lupus nephritis in the F1 recipients was strongly inhibited and immunopathological parameters such as anti-DNA antibodies, circulating immune complexes (CIC) and splenic immunoglobulin-producing cells (IgPC) were markedly reduced. The injection of CD4+ (L3T4+) T cells into F1 recipients did not result in similar effects. These findings suggest that the development of autoimmune disease could be ameliorated by CD8+ cells responding to MHC class I antigens. The significance of the data is discussed in terms of the treatment of autoimmune diseases. PMID- 1424285 TI - The putative role of cytokines in the induction of primary anti-phospholipid syndrome in mice. AB - Antiphospholipid syndrome (APLS) is characterized by thrombocytopenia, thromboembolic phenomena and recurrent fetal loss, associated with anti cardiolipin antibodies (ACA) and/or lupus anticoagulant. The syndrome may be primary or may be associated with other conditions such as systemic lupus erythematosus (SLE). In this study we induced primary APLS following immunization of BALB/c mice with a human monoclonal ACA (H-3). Analysis of the cytokine profile of the mice with experimental APLS indicated low production of IL-2, IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by concanavalin A (Con A)-stimulated splenocytes of H-3 immunized mice. It seems that the low levels of IL-3 and GM-CSF have a potential role in the fetal loss of the APLS. Whatever the mechanism of IL-3 and GM-CSF in preventing fetal loss, these results may have therapeutic bearing on the reproductive outcome in women and other species with APLS. PMID- 1424286 TI - Circulating antibodies to heat-shock protein 60 in Crohn's disease and ulcerative colitis. AB - Heat-shock proteins (HSPs) are highly conserved immunogenic intracellular molecules that are induced by inflammatory mediators and may induce autoimmune phenomena in vivo. We have recently demonstrated the increased expression of HSP 60 in the colonocytes of patients with ulcerative colitis. To study further the role of HSP-60 in inflammatory bowel disease, we have now measured antibodies to recombinant mycobacterial HSP-65 (a member of the HSP-60 family) in patients with Crohn's disease, ulcerative colitis, healthy volunteers and, as disease controls, patients with confirmed bacterial diarrhoea. In comparison with healthy controls (n = 20; median level of 89 ELISA units; range 24-292), serum IgA HSP-60 antibodies were elevated in Crohn's disease (n = 21; 157; 57-364; P < 0.05) and active ulcerative colitis (n = 16; 188; 58-373; P < 0.01) but not bacterial diarrhoea (n = 10; 106; 51-285). Increased IgA HSP-60 antibody levels in patients with inflammatory bowel disease may occur as the result of HSP release from injured gut epithelium; alternatively, increased intestinal permeability could facilitate mucosal access of luminal antigens and the generation of cross reactive anti-bacterial HSP antibodies. PMID- 1424287 TI - Expression of T cell receptors alpha beta and gamma delta in the ileal mucosa of patients with Crohn's disease and with spondylarthropathy. AB - The expression of the alpha beta and gamma delta heterodimer of the T cell receptor (TCR) was studied in normal human ileal mucosa or in ileal biopsies featuring Crohn's disease or acute and chronic spondylarthropathy-related gut inflammation. With an immunohistochemical technique we demonstrated that the increase of mucosal lymphocytes per mm mucosa in Crohn's disease and spondylarthropathy-related ileitis is exclusively due to expansion of the alpha beta + T cell compartment. In Crohn's disease and chronic ileitis observed in some spondylarthropathy patients the alpha beta + T cells were increased amongst intraepithelial lymphocytes (IEL). The lamina propria lymphocytes (LPL) were augmented in all studied inflammatory conditions. The gamma delta + T cells showed no changes in IEL or LPL and their proportions were not altered. They were evenly dispersed throughout the ileal mucosa and did not seem to participate in the inflammatory process. This study confirms that gamma delta T cells are a distinct subset in the intestinal mucosa. The increase in alpha beta + T cells suggests augmented mucosal antigen handling and involvement of the major histocompatibility complex in the pathogenesis of spondylarthropathy-related gut inflammation and Crohn's disease. PMID- 1424288 TI - The role of T cells and the effect of hydrocortisone on interleukin-4-induced IgE synthesis by non-T cells. AB - The role of T cells for IL-4-induced IgE synthesis by peripheral blood mononuclear cells (PBMC) was investigated. The removal of monocytes from PBMC abolished IL-4-induced IgE synthesis. When PBMC were separated into T and non-T cells, non-T cells alone were not able to secrete significant amounts of IgE in the presence of IL-4. Depending on the separation procedure, the reconstitution of non-T cells with T cells prepared by rosetting did not restore IgE secretion, whereas T cells obtained by the use of anti-CD3 antibodies could co-induce IgE formation. However, when the T cells were first irradiated, large amounts of IgE were produced, which strongly exceeded those found in unseparated PBMC cultures. IL-4-induced IgE synthesis was also obtained in co-cultures of formaldehyde-fixed T cells with non-T cells. Furthermore, not only autologous but also allogeneic T cells, which have been irradiated or fixed, could provide the costimulatory effect on IgE formation by non-T cells in the presence of IL-4. Mitogenically pre activated T cells, however, were not able to support IgE synthesis. Hydrocortisone (HC) potentiated the IL-4-induced IgE synthesis by PBMC and enabled non-T cells to secrete IgE in the presence of IL-4. Adding both HC and T cells led to a marked synergistic effect on IL-4-induced IgE production. We conclude that monocytes are required for the induction of IgE synthesis in PBMC in addition to T cells and IL-4. Our results support the view that the T cell signal is delivered via cognate and non-cognate T/B cell membrane interaction. Furthermore, active and proliferating T cells rather suppress IgE synthesis. Finally, HC appears to be a potent alternative stimulus, which bypasses the necessity for T cells in IL-4-induced IgE formation. PMID- 1424289 TI - Production of serum amyloid A and C-reactive protein by HepG2 cells stimulated with combinations of cytokines or monocyte conditioned media: the effects of prednisolone. AB - The hepatic production of the acute phase proteins in response to inflammatory cytokines, and the interaction of corticosteroids within this response, has been the subject of considerable recent research. In this study we have examined the effects of the corticosteroid prednisolone on the production of IL-1 alpha and IL 1 beta by lipopolysaccharide (LPS)-stimulated monocytes, and the ability of the monocyte conditioned media (MOCM) obtained under these conditions to induce human hepatoma HepG2 cells to produce serum amyloid A (SAA) and C-reactive protein (CRP). We also examined the production of SAA and CRP by HepG2 cells exposed to different combinations and concentrations of recombinant human (rh) IL-1 alpha, rhIL-1 beta, rhIL-6, recombinant human tumour necrosis factor-alpha (rhTNF-alpha) and prednisolone. The findings indicate: (i) prednisolone substantially inhibits the production of both IL-1 alpha and IL-1 beta by LPS-stimulated monocytes. The MOCM from prednisolone-treated monocytes induced less SAA and CRP production by HepG2 cells; (ii) IL-1 alpha and IL-1 beta both induced CRP and SAA synthesis by HepG2 cells, but only in the presence of IL-6. IL-1 beta was the more potent inducer for SAA production, but for CRP production IL-1 alpha and IL-1 beta were equivalent; (iii) prednisolone enhances the production of SAA by HepG2 cells, but does not enhance the production of CRP; (iv) TNF-alpha in the presence or absence of IL-6 and/or prednisolone did not induce the production of SAA or CRP by HepG2 cells. These findings offer a tenable solution to a disparate production of SAA compared with CRP in corticosteroid-treated cystic fibrosis (CF) patients. PMID- 1424290 TI - Secretory IgA are elevated in both saliva and serum of patients with various types of primary glomerulonephritis. AB - Secretory immunoglobulin A (IgA) was determined by means of an enzyme-linked immunosorbent assay (using as capture antibody an MoAb specific for secretory component) in saliva and serum from 46 patients with IgA mesangial nephritis (IgAGN), 36 with an idiopathic nephrotic syndrome (INS), 30 with an idiopathic membranous nephropathy (MGN) and 40 healthy controls. Secretory IgA levels were elevated in both saliva and serum of patients with primary glomerulonephritis (P < 0.05; Mann-Whitney test) regardless of the histological type of the primary glomerulonephritis. Salivary IgA1 and IgA2 levels were increased in the saliva of patients with IgAGN, INS and MGN (P < 0.05; Mann-Whitney test). The monomeric/total IgA ratio, and interferon-gamma and soluble IL-2 receptor levels, in saliva did not differ between the patients and controls (P > 0.05; Mann Whitney test). We conclude that the mucosal immune system is activated in forms of glomerulonephritis other than IgAGN. PMID- 1424292 TI - Urinary excretion of nitrite and nitrate in experimental glomerulonephritis reflects systemic immune activation and not glomerular synthesis. AB - In immune-induced glomerulonephritis (gn), glomeruli (gl) synthesize nitric oxide (NO), and urinary nitrite (NO2-) excretion is increased. In mammals on a low nitrate (NO3-) diet, urinary NO3- is a measure of endogenous NO3- synthesis. Excretion is increased after administration of macrophage activators, reflecting induction of NO production. To determine whether increased urinary NO2- gn is due to glomerular synthesis we studied urinary NO2-/NO3- in accelerated nephrotoxic nephritis induced by preimmunization with rabbit immunoglobulin G (IgG), followed by rabbit anti-rat nephrotoxic globulin, and in control rats similarly preimmunized with rabbit IgG, but followed by normal rabbit serum. Both urinary NO2- and NO3- were increased by i.p. preimmunization with rabbit IgG (peak 463 +/ 171 nmol NO2-/60.3 +/- 9.4 nmol NO3-/24 h, P < 0.001 for both NO2- and NO3- compared with preimmunization levels). Repeat immunization with i.v. rabbit anti rat nephrotoxic globulin (nephritic rats) or normal rabbit globulin (control rats) again increased urinary NO2- and NO3-. There was no statistically significant difference in urinary NO2- and NO3- levels between nephritic rats where globulin had nephrotoxic activity and the control rats injected with normal rabbit globulin, despite increased NO2- synthesis in ex vivo nephritic glomeruli after nephrotoxic globulin (7.9 +/- 1.9 nmol/2000 gl/48 h; controls 3.2 +/- 1.0 nmol/2000 gl/48 h). Thus neither urinary NO2- nor NO3- levels reflect local activation of the NO pathway in glomeruli. As reported for other stimulants, we show here that systemic stimulation with foreign antigen increased NO synthesis. PMID- 1424291 TI - Isolation and characterization of the tubular basement membrane antigen associated with human tubulo-interstitial nephritis. AB - The target antigen, a 54-kD glycoprotein (gp54), reactive with sera from patients with anti-tubular basement membrane (anti-TBM) nephritis, was isolated from collagenase-digested (CD) bovine TBM. The purified gp54 was shown to be non collagenous by amino acid analysis, and to be a unique basement membrane component by amino-terminal sequencing. The nephritogenicity of gp54 was demonstrated by immunizing strain XIII guineapigs with purified gp54, and producing anti-gp54 antibody and tubulo-interstitial nephritis. Anti-gp54 antibody, affinity-purified from sera of patients with anti-TBM nephritis, bound by immunoblotting to 54-kD and, to a lesser extent, 48-kD components of partially purified human CD-TBM. Indirect immunofluorescence showed that gp54 was present in the basement membrane of proximal tubules of the kidneys of normal human, cow, rabbit, guineapig and Brown-Norway rat but not in Lewis rat. Immunoelectron microscopy revealed localization of gp54 along the interstitial side of the TBM and its association with interstitial collagen fibres. These results indicate that gp54 is the nephritogenic antigen involved in tubulo-interstitial nephritis, and is unique in chemical characteristics and localization in the kidney. PMID- 1424293 TI - Immunohistochemical characterization of infiltrating mononuclear cells in the rat heart with experimental autoimmune giant cell myocarditis. AB - The pathogenesis of giant cell myocarditis remains unclear. Subsets of inflammatory infiltrating cells may reflect the pathogenesis and etiology of the disease. Therefore, we examined subsets of infiltrating mononuclear cells in the heart of the rat with experimental giant cell myocarditis. Lewis rats were immunized with cardiac myosin in Freund's complete adjuvant (FCA). Severe myocarditis characterized by congestive heart failure and multinucleated giant cells were elicited. The lesions were composed of predominant mononuclear cells, polymorphonuclear neutrophils and fragments of degenerated myocardial fibres. The subsets of infiltrating mononuclear cells were investigated using MoAbs against rat CD4+ T cell (W3/25), CD8+ T cell (CX8), B cell (OX33) and macrophage (OX42). By serial examination, bound immunoglobulin could only be found on degenerated myocardial fibres. In this model, most infiltrating mononuclear cells were composed of macrophages and CD4+ T cells. The frequencies of macrophages and CD4+ T cells were 73.7% and 13.8%, respectively. CD8+ T cells were scarce and B cells were rare in the lesions. The frequencies of CD8+ T cells and B cells were 4.5% and 0.4%, respectively. The dominance of macrophages and CD4+ T cells was the constant finding among the sites of the lesions and throughout the course of the disease. These characteristic subsets of infiltrating cells were in contrast to those of murine viral myocarditis which were mainly composed of natural killer (NK) cells and CD8+ T cells. Clarifying the subsets of infiltrating cells in myocarditis may contribute to differential diagnosis of myocarditis between viral and autoimmune types. From this study, the pathogenesis of experimental autoimmune giant cell myocarditis seemed to be closely related to CD4+ T cells and macrophages. PMID- 1424295 TI - Origin of urinary epidermal growth factor in humans: excretion of endogenous EGF and infused [131I]-human EGF and kidney histochemistry. AB - 1. This study examined (i) whether blood-infused epidermal growth factor (EGF) can pass into urine; (ii) whether infused labelled EGF behaves like endogenous plasma immunoreactive EGF; and (iii) which parts of the human nephron show morphological evidence of EGF synthesis? 2. We infused human [131I]-EGF into a volunteer. After 6 min, only 66% of the plasma counts represented intact EGF. At the end of infusion, the T1/2 of EGF was calculated to be 1.6 min. The tail of the curve lasted for at least another 2 h. The total excretion of the labelled EGF was 2.45% of the infused dose and was proportional to the urine volume. 3. After a water load, the excretion of endogenous EGF was, on the contrary, inversely related to urine volume. 4. Immunohistochemically, human kidneys were not stained by monoclonal anti-EGF antibodies but showed positive in situ hybridization for EGF mRNA in the nuclei of glomerular mesangial cells, distal convoluted tubules and collecting tubules. 5. We conclude that human kidneys synthesize EGF and release it into urine. Plasma-derived EGF constitutes under normal conditions only a small part of the urinary EGF. Contrasting volume dependency of the excretion of endogenous and [131I]-EGF requires further study and cautions against extrapolating results obtained with labelled EGF to physiological conditions. PMID- 1424294 TI - Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population. AB - The study of 87 adults of different ages, including 15 centenarians, selected for their healthy status, showed that profound changes of humoral immunity occur throughout life. In particular, a statistically significant age-related increase of the serum level of immunoglobulin classes (IgG and IgA but not IgM) and IgG subclasses (IgG1, 2 and 3, but not IgG4) was detected. A parallel age-related decrease of circulating B cells was also observed. The hypothesis of a complex derangement of B cell function and/or compartmentalization with age is put forward, together with the proposal that healthy centenarians (as representative of successful ageing) may be helpful in identifying the physiological age-related modifications of the immune system. PMID- 1424296 TI - Endothelin-3-induced microvascular incompetence and mitochondrial damage in rat myocardium. AB - 1. To determine the possible role of an endothelin in the development of postischaemic microvascular incompetence, isolated buffer-perfused rat hearts were perfused with endothelin-3 (ET-3) in phosphate buffer. 2. ET-3 produced a reduction in coronary flow rate, heart rate and arrhythmia. There was a marked reduction in the density of competent capillaries, and the myocytes showed vacuolation and mitochondrial damage in regions where microvascular incompetence was most severe. 3. These results indicate that ET-3 can substantially reduce microvascular perfusion in the heart and can also cause damage to the myocyte. PMID- 1424297 TI - Arachidonic acid metabolism in nicotine-treated rats and nicotine-incubated rabbit aortic smooth muscle cells. AB - 1. The changes in plasma levels of thromboxane-B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were examined in rats given 5, 25, 50 or 100 micrograms/mL nicotine in drinking water for 10 days. 2. The effect of nicotine on prostacyclin (PGI2) synthesis from endogenous arachidonic acid by cultured rabbit aortic smooth muscle cells was also studied. 3. Plasma levels of TXB2 were increased dose-dependently by treatment for 10 day with nicotine. 4. 6-Keto-PGF1 alpha values were lowered dose-dependently, both in the plasma of nicotine treated rats and in rabbit aortic smooth muscle cells incubated with the alkaloid. 5. The results suggest that endogenous synthesis of thromboxane-A2 and PGI2, as reflected by TXB2 and 6-keto-PGF1 alpha levels, respectively, is influenced by nicotine treatment. These findings may be related to cardiovascular diseases associated with cigarette smoking, but further studies are needed. PMID- 1424298 TI - Angiotensin-converting enzyme inhibition causes deterioration in renal function in one-kidney Goldblatt hypertensive rats with and without renal arterial stenosis. AB - 1. The renal and hypotensive effects of a new angiotensin-converting enzyme (ACE) inhibitor, cilazapril, were evaluated in 18 one-kidney, one-clip Goldblatt hypertensive rats (1K1C), 10 one-kidney normotensive rats (1K) and eight 1K1C rats with acute unclipping (1KU). Cilazapril was infused intravenously (25 micrograms/kg per min) into anaesthetized rats, and the arterial blood pressure (BP) and renal clearance of rats were measured. 2. In 1K rats, cilazapril reduced BP from 123 +/- 4 to 117 +/- 4 mmHg (P < 0.05), and produced diuresis, natriuresis and kaliuresis without significantly changing glomerular filtration rate (GFR). 3. In 1K1C rats, cilazapril significantly reduced BP (from 157 +/- 5 to 143 +/- 6 mmHg; P < 0.05), GFR (14.4 +/- 6.7%), urine flow (27.1 +/- 8.5%) and sodium excretion (39.4 +/- 7.4%). Mechanically graded reductions of renal arterial pressure alone also produced parallel decreases in GFR and renal excretory function. 4. In 1KU rats, removal of the renal arterial clip significantly decreased BP and increased renal function. Subsequent infusion of cilazapril further reduced BP and urinary excretions of sodium and water but did not significantly change GFR. 5. These results suggest that the renal function of the 1K1C hypertensive model is pressure-dependent, and that ACE inhibitor exerts a mild antihypertensive effect but causes a pressure associated reduction in renal function. Furthermore, the detrimental effect of ACE inhibitor on the residual kidney persists after acute surgical correction of the stenosis. PMID- 1424299 TI - Response of plasma renin-angiotensin system to a single captopril administration in patients receiving long-term treatment with captopril. AB - 1. The responses of angiotensin II (AII), AIII, aldosterone and plasma renin activity (PRA) to a single dose of captopril were investigated in hypertensive patients receiving long-term (more than 1 year) captopril therapy (CT patients) and compared with those of non-treated hypertensive patients (NT patients). 2. Baseline levels of AII and aldosterone were significantly lower in CT patients than in NT patients. AIII tended to be lower and PRA was slightly higher in CT than in NT patients, but these differences were not significant. 3. A single administration of captopril (50 mg orally) significantly decreased plasma levels of AII, AIII and aldosterone as well as blood pressure in both CT and NT patients. 4. These results demonstrate that chronically repeated administration of captopril to hypertensive patients effectively reduces the daily blood pressure and concomitantly the plasma AII level to acceptable levels in patients with no experience of ACE inhibition. PMID- 1424300 TI - In vivo and in vitro effects of atrial natriuretic peptide on renin release. AB - 1. This study investigated the effect of atrial natriuretic peptide on renin release from the kidney. The in vitro direct effect was examined in the animal experiment using renal cortical slices of rat, and the in vivo effect was observed in the human infusion study. 2. In the in vitro experiments, alpha-human atrial natriuretic peptide (alpha-hANP) ranging 10(-9) to 10(-6) mol/L did not change the basal renin release rate from the renal cortical slices (-9% at 10(-6) mol/L, NS). Isoproterenol (10(-6) mol/L) increased renin release by 40% (P < 0.001), whereas angiotensin II (10(-6) mol/L) suppressed it by 48% (P < 0.001). However, alpha-hANP did not affect the stimulative effect of isoproterenol or the inhibitory effect of angiotensin II. 3. Also in the human study, infusion of 25 ng/kg per min alpha-hANP failed to change the plasma renin activity in normotensive subjects (-4%) or patients with essential hypertension (+5%), or even in patients with raised renin levels such as renovascular hypertension (+10%) or congestive heart failure (-13%). 4. These results put forth negative views on the direct involvement of atrial natriuretic peptide in renin release from the juxtaglomerular apparatus. PMID- 1424301 TI - Mechanism and prevention of chronic colonic inflammation with trinitrobenzene sulfonic acid in rats. AB - 1. The role of prostanoids in experimental colitis with trinitrobenzene sulfonic acid (TNBS) in rats was investigated. The effects of cyclosporine A (CsA) on the development of experimental colitis were also examined. 2. Five kinds of prostanoids were detected in rat colonic tissue by high performance liquid chromatography. These were 6-keto-prostaglandin (PG) F1 alpha, PGF2 alpha, PGE2, PGD2 and thromboxane B2. 3. In TNBS-induced experimental colitis, all prostanoid concentrations except PGD2 increased, although the time courses differed from each other. 4. Medication with indomethacin markedly reduced prostanoid concentrations in TNBS-induced colitis. However, indomethacin did not show any effect on damage scores. 5. Cyclosporine A reduced damage scores 14 days after TNBS treatment, and the protective effects were observed, whereas CsA did not affect colonic tissue prostanoid concentrations. 6. Prostanoids might be produced secondarily in the genesis of TNBS-induced colitis, although they may attenuate the inflammatory response. It was also suggested that CsA was likely to have therapeutic effects on experimental colitis by inhibiting the immune reaction with TNBS, which induced the chronic inflammation. PMID- 1424302 TI - Different biventricular remodelling of myosin and collagen in pulmonary hypertension. AB - 1. To clarify the metabolism of contractile and non-contractile proteins of the ventricles during the development of right ventricular hypertrophy (RVH) and accompanying congestive heart failure (CHF) in response to a pressure overload, monocrotaline was injected subcutaneously into Sprague-Dawley (SD) rats. Myosin isoenzymes (MIE) were analysed by pyrophosphate gel electrophoresis under non dissociating conditions. Acid-soluble collagens were analysed by an improved, noninterrupted sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS PAGE). Tissue collagen content was also measured after the estimation of hydroxyproline concentration in tissues. 2. Monocrotaline induced RVH, but not left ventricular hypertrophy, at 2 weeks after the injection of monocrotaline, with severe RVH with CHF present at 4 weeks. In the right ventricles (RV) treated with monocrotaline, MIE shifted significantly from V1 to V3 at 2 weeks. The shift of MIE was more pronounced at 4 weeks. The proportion of type III collagen increased significantly compared with controls at 2 weeks. At 4 weeks, the proportion of types III and V collagens increased significantly compared with controls. 3. In left ventricles (LV) treated with monocrotaline, a similar but less remarkable shift of MIE was observed without remodelling of collagen types at 2 and 4 weeks. The concentration of collagen in either the RV or LV treated with monocrotaline showed no significant changes at 2 and 4 weeks compared with controls. 4. These results demonstrate a remodelling of the contractile and non contractile proteins during the development of RVH and accompanying CHF, and provide evidence for changes in protein metabolism of the counterpart of RV (i.e. the LV). These results may provide important insights into the pathophysiology of adaptive or non-adaptive cardiac hypertrophy in response to a pressure overload. PMID- 1424303 TI - Soluble interleukin-2 receptor levels in lupus nephritis. AB - Soluble interleukin-2 receptor (IL-2R) levels were measured and correlated prospectively with clinical, histologic and serologic findings over a 9-month period in 62 lupus patients. Initially, 39 patients had clinical nephritis and 23 patients did not have nephritis. The 62 lupus patients has significantly higher IL-2R than 15 normal controls, most of this difference attributable to patients with nephritis. During lupus nephritis flare 9 of 10 patients showed significant elevations of IL-2R while only 6 of the 10 patients showed either elevation of anti-DNA antibody or decrease in CH50. During disease remission or stable clinical activity changes in IL-2R levels paralleled changes in anti-DNA antibody and CH50. Nephritis patients with cellular proliferative histology had significantly higher IL-2R levels than those with membranous or mesangial nephropathy. IL-2R correlated strongly with histologic activity and chronicity indices, IgG and C3 deposition whereas anti-DNA antibody and CH50 levels did not. IL-2R levels did not correlate with serum creatinine suggesting that elevations of IL-2R were not simply due to decreased clearance. These observations suggest that serum IL-2R level is a useful marker of disease activity in lupus nephritis and may serve as a helpful adjunct in management of this disorder. PMID- 1424304 TI - Detection and clinical usefulness of urinary interleukin-6 in the diseases of the kidney and the urinary tract. AB - Interleukin-6 (IL-6) plays a key role in inflammatory and immune responses in the host. In the present study, the IL-6 activity in urine from patients with various renal diseases was examined to elucidate the pathological and clinical significance of urinary IL-6. In patients with mesangial proliferative glomerulonephritis (mes-PGN) including, IgA nephropathy, the urinary IL-6 activity tended to increase with the progression of mesangial hypercellularity. In four patients with IgA nephropathy, urinary IL-6 activity increased markedly but transiently during episodes of acute exacerbation associated with upper respiratory tract infection. In addition, it was demonstrated that urine from patients with other types of PGN such as poststreptococcal acute glomerulonephritis and membrano-proliferative glomerulonephritis contained large quantities of IL-6. However, the levels of urinary IL-6 activity were almost within the normal range in non-proliferative glomerular diseases such as membranous nephropathy, minimal change nephrotic syndrome and lupus nephritis (WHO class I and V), non-glomerular bleeding and orthostatic proteinuria. It should be noted that a marked increase in urinary IL-6 was often observed in the patients with urinary tract infection. These results indicated that IL-6 in urine might be derived from various types of cells participating in inflammatory reactions not only in the renal parenchyma but also in the urinary tract. PMID- 1424306 TI - Traumatic rupture of the urinary tract in a patient presenting nephrogenic diabetes insipidus associated with hydronephrosis and chronic renal failure: case report and review of the literature. AB - We report the case of a 34-year-old Japanese man suffering from a nephrogenic diabetes insipidus (NDI) associated with bilateral hydronephrosis, hydroureters and enlarged trabeculated bladder without obstruction. He also presented with chronic renal failure which has rarely occurred in similar cases. The patient was admitted after a traumatic rupture of the left urinary tract which had never been described until now in NDI. He was treated successfully by transient peritoneal and vesical drainages. This paper focuses on the very rare complication of chronic renal failure secondary to hydronephrosis in cases of NDI. The literature of this association is reviewed. PMID- 1424305 TI - A prospective study of urine and serum myoglobin levels in patients with acute rhabdomyolysis. AB - Serum and urine myoglobin levels, measured by radioimmunoassay, were determined prospectively in eight patients with acute rhabdomyolysis, within 24 hours of admission. Five patients had urine myoglobin concentrations greater than 1,000 ng/ml (normal < 5 ng/ml); four of these patients subsequently developed acute renal failure. In three patients whose urinary myoglobin levels ranged from 19 to 275 ng/ml, acute renal failure did not occur. This difference in the occurrence of acute renal failure between the two patient groups was statistically significant (p < 0.05). Mean peak serum creatinine was significantly higher in the patients with high urine myoglobin (6.4 +/- 1.3 mg/dl) compared to those with low urine myoglobin (2.2 +/- 0.3 mg/dl), p < 0.02. There was no statistical correlation between level of serum creatine phosphokinase and serum or urine myoglobin, although the serum and urine myoglobin levels correlated well with each other. These findings suggests that among other factors, urine myoglobin may need to reach a critical level in order for myoglobinuric renal failure to ensue. PMID- 1424307 TI - Circulating and excreted forms of atrial natriuretic peptide in healthy subjects and patients with renal diseases. AB - The immunoreactivity of plasma and urine atrial natriuretic peptide (ANP) was measured in patients with renal disease and in healthy volunteers. The molecular forms of ANP in these subjects were estimated by gel permeation chromatography and reverse phase high performance liquid chromatography. No significant increase in plasma ANP was observed in patients with nephrotic syndrome or non-oliguric chronic renal failure compared to healthy volunteers. However, plasma ANP levels were significantly increased in patients on hemodialysis (normal 18.6 +/- 11.4 fmol/ml; hemodialysis 91.2 +/- 69.9 fmol/ml, p < 0.01). Chromatographic analyses revealed that plasma ANP consisted of only alpha-ANP or combined alpha- and gamma ANP in healthy volunteers and in nephrotic patients, whereas beta-ANP frequently appeared in the plasma of both dialyzed and non-dialyzed chronic renal failure patients. Excreted forms, except in subjects free from renal disease where gamma ANP may serve as a potential marker of glomerular injury in humans. PMID- 1424308 TI - Thyrotropin-releasing hormone: pharmacokinetic and pharmacodynamic properties in chronic renal failure. AB - The pharmacokinetics of thyrotropin-releasing hormone (TRH) were determined following a single i.v. administration in ten patients with chronic renal failure (CRF) maintained on chronic hemodialysis and in six normal subjects. A TRH-test (200 micrograms) was performed in all subjects on nondialysis days and was followed by sequential venous blood sampling at 0, 2, 5, 10, 20, 30 and 60 min. Plasma TRH and serum concentrations of TSH, T4, FT4 and T3 were measured by specific and sensitive RIA's. Serum thyroid hormone concentrations were lower in the hemodialysis patients than in the normals (p < 0.001). Basal TRH and TSH levels were similar in patients and in controls, however, a blunted response of TSH to TRH in CRF (3.8 +/- 2.4 vs. 11.2 +/- 2.6 mU/l, p < 0.001) was observed. Mean peak TRH concentrations (Cmax) were 34.445 (11.085, SD) fmoles/ml in CRF and only (13,400 (1.020) in the normals 2 min after TRH administration (tmax). The mean elimination half-life (t1/2) of TRH was 16 min in CRF and 6.5 min in normals (p < 0.001). The metabolic clearance rate (MCR) was markedly lowered in CRF, 58.3 (19.1) compared to normals (82.2 [15.3] l/m2/day, p < 0.001). The area under the plasma concentration-time curve (AUC) was 57.529 (28.562) fmoles.ml-1.min in CRF and 37.339 (5.026) (p < 0.005) in normals. These findings indicate that the pharmacokinetic properties of TRH are impaired in CRF. The kidney might be an important catabolic organ for exogenous TRH. Dosing schedules of TRH require possible adaptation to renal function. PMID- 1424309 TI - Impact of dialysis modality on body composition in patients with end-stage renal disease. AB - Loss of muscle mass and altered body fat distribution (i.e. increased central fat stores in the presence of normal peripheral fat stores) have been reported in patients on hemodialysis (HD), when compared to normal volunteers. Whether treatment of end-stage renal disease (ESRD) with continuous ambulatory peritoneal dialysis (CAPD) would alter body composition in a different manner than HD is unknown. To answer this question, two groups (n = 11 each) of male patients with ESRD (matched for age, residual renal function, body weight and body height as well as physical activity) were studied. Muscle mass and body fat distribution were assessed using computed tomography. Mid-thigh muscle area, peripheral and central fat stores were similar between the two groups of dialysis patients. In both patient groups muscle mass and fat stores were independent of duration of dialysis, age, daily protein intake and residual renal function. In CAPD-patients mid-thigh muscle area was correlated with plasma albumin (r = 0.56, p < 0.05), while serum cholesterol level was correlated with mediastinal fat area (r = 0.81, p < 0.01). The present results indicate that both treatment modalities of ESRD (HD vs CAPD) result in similar changes of body composition. Despite continuous glucose loading in CAPD-patients, neither central nor peripheral fat stores are increased in these subjects compared with HD treated patients. PMID- 1424310 TI - Surgical treatment of hemodialysis-related shoulder arthropathy. AB - Thirteen patients with hemodialysis-related shoulder arthropathy were treated either with arthroscopic synovectomy or with open surgery. Arthroscopic synovectomy was performed in eight patients who had shoulder pain, shoulder immobility or both but did not have cystic bone lesions. The therapy was effective for pain relief and improvement of shoulder function for six months but in 12 months the shoulder pain reappeared in most of the patients. Open surgery was done in 5 patients who, in addition to shoulder pain and immobility, had humeral head bone cysts. Resection of the deposited mass on the biceps tendon sheath, of hypertrophied synovium and bursa as well as curettage of cysts and calcium hydroxyapatite ceramic implantation were performed. The therapy was effective for pain relief throughout the follow-up period (12 months). No adverse effects were noted for either procedure. Resected specimens of the synovia contained amyloid as indicated by a positive Congo-red stain by light microscopy and the presence of amyloid fibrils by electron microscopy. Deposition of amyloid in the biceps tendon sheath, synovium and bursa and invasion of the humeral head by amyloid were observed upon open surgery. The results suggest that the resection of deposited material induces the improvement of the shoulder arthropathy. PMID- 1424311 TI - Propafenone pharmacokinetics in uremic patients treated by peritoneal dialysis. PMID- 1424312 TI - Importance of nosocomial transmission of hepatitis C virus infection in dialysis units. PMID- 1424313 TI - Focal glomerular sclerosis (FGS)-like lesions are not rare in preeclampsia. PMID- 1424314 TI - Diabetic nephropathy: eleven-year survival on hemodialysis with good quality of life. PMID- 1424315 TI - Sequential clinical and immunological follow-up shows similar evolution during the first trimester after renal transplantation in patients receiving azathioprine or not. PMID- 1424316 TI - Diuretics potentiate the angiotensin converting-enzyme inhibitor-associated acute renal dysfunction. PMID- 1424317 TI - Production of tumor necrosis factor-alpha by glomerular macrophages in nephrotoxic serum nephritis. PMID- 1424318 TI - Laparoscopic cholecystectomy in a patient on continuous ambulatory peritoneal dialysis. PMID- 1424319 TI - Non-Alzheimer non-Pick dementia with Fahr's syndrome. AB - Five patients with non-Alzheimer non-Pick dementia combined with Fahr's syndrome were studied. Atypical clinical pictures emerged from an evaluation of these cases. Their symptoms and signs could be attributed neither to Alzheimer's disease nor to Pick's disease but to a partial mixture of both. The neuropathological changes were characteristic, and the common findings were as follows: 1) the absence of senile (neuritic) plaques, 2) the widespread presence of numerous neurofibrillary tangles throughout the neocortex, 3) a calcareous deposition of Fahr's type, 4) a circumscribed cerebral atrophy in the temporal or/and frontal lobes, 5) a moderate or severe demyelination and fibrous gliosis in the white matter of the atrophied areas and 6) a mild or moderate neuronal loss in the nucleus basalis of Meynert. These neuropathological changes were not due to Alzheimer's disease nor to Pick's disease. Similar cases reported previously were reviewed. PMID- 1424320 TI - Trimethyltin poisoning: report of a case with postmortem examination. AB - A 48-year old woman died six days after intake of an unknown amount of trimethyltin (TMT). Early clinical features were tinnitus, lightheadedness, aggression and episodes of unresponsiveness. She gradually developed coma and died of multiorgan failure. The main pathologic findings were confined to the nervous system which revealed generalized chromatolysis of the neurons in the brain, spinal cord and spinal ganglia. Recent neuronal necrosis, which probably was caused by toxic effect of TMT, was present in the fascia dentata of the hippocampus and in the spinal ganglia. Recent necrosis was also present in the pyramidal cell layer of the hippocampus, cerebral cortex, basal ganglia and Purkinje cell layer of the cerebellum, but some of these changes could have been caused by an anoxic episode shortly before death. Electron microscopy revealed marked accumulation of lysosomal dense bodies and disorganization of the granular endoplasmic reticulum in the neurons. The findings were similar to those described in experimental TMT intoxications. Cytoplasmic zebra bodies, which were described in a previous human case of TMT intoxication, were not observed in the present case. PMID- 1424321 TI - Patient selection for assisted reproduction. AB - Patient selection is a critical factor in influencing results in assisted reproduction. Patients should be assessed individually in terms of all relevant fertility factors including age, duration and aetiology of infertility and psycho social attitudes so that an approximate prognosis of their management can be made. Restrictive criteria for patient selection will enhance a programme's results but at the expense of depriving some couples of their only chance of conception. The best overall management of each individual infertile couple should always remain the main criteria for selection into a particular assisted reproduction programme. PMID- 1424322 TI - In vitro fertilization in the natural cycle. AB - In vitro fertilization in the natural or spontaneous reproductive cycle was first described by Edwards and his colleagues in 1980 following the birth of their first natural cycle IVF baby 2 years earlier. Many groups attempted to follow their lead but it was almost ten years later that the next publication of success appeared (Foulot et al, 1989). The concept of IVF in the natural cycle is particularly attractive and so in 1987 our group also started evaluating the technique. Initial success in the patients with tubal lesions was not translated to patients with other infertility indications. Unfortunately the technique as initially developed was relatively inefficient with significant procedural losses at each stage. Over the succeeding four years a number of changes have been introduced and the efficiency considerably improved. Although these changes have improved take-home baby rates, overall pregnancy rates per embryo have not altered and are still lower than spontaneous in vivo pregnancy rates. It is likely that in the future, with current developments in culture techniques and greater understanding of gamete biology, this situation will change significantly. PMID- 1424323 TI - GnRH agonists and antagonists in assisted reproduction. PMID- 1424324 TI - The role of treatment with growth hormone in infertile patients. AB - The reality of the interaction of GH and its mediator, IGF-I, with gonadotrophins is now established. The results of these studies and others have obvious implications, both physiologically and clinically. Co-treatment with GH augments the gonadal response to gonadotrophins, and it seems to be of particular value in patients who are poor responders to gonadotrophin treatment and who have pituitary hypofunction induced surgically, idiopathically (hypogonadotrophic hypogonadism) or medically (treatment with GnRH analogues). There is conflicting evidence as to whether the observed effect of GH is exerted directly on the ovary or mediated through IGF-I. Treatment with GH causes a distinct increase in serum IGF-I concentrations, which correlate with, but are always higher than, follicular fluid levels, suggesting that GH stimulates hepatic production of IGF I and that the effect on the ovary is endocrine. Further research will, hopefully, clearly define the precise therapeutic role of GH in the induction of ovulation, the selection of the most appropriate group of patients to be treated, and the minimum dose of GH needed to sensitize the ovary. Further studies are also needed to explore the action of GH and to define the role of IGF-I in the process of follicular development. PMID- 1424325 TI - Vaginal ultrasound in assisted reproduction. AB - Vaginal scanning of the ovaries and the uterus is a diagnostic and monitoring tool of utmost importance in assisted conception. Although the value of ultrasound for monitoring follicular growth has been questioned, few groups working on assisted conception do not use it. Follicle aspiration under the guidance of vaginal sonography is the method of choice. With such a simple and safe technique available, using laparoscopy for retrieving oocytes for assisted conception cannot be justified. The introduction of ultrasound-guided transvaginal retrograde tubal catheterization has meant that laparoscopic GIFT and ZIFT procedures will probably soon be unnecessary. Vaginal sonography is one of the most clinically important diagnostic instruments in assisted conception. PMID- 1424326 TI - Advances in methodologies aimed at enhancing the viability of in vitro cultured human embryos. PMID- 1424327 TI - Cryopreservation of human embryos. AB - This chapter describes general cryobiological principles and the different methods for cryopreservation of supernumerary human embryos obtained after several procedures for medically assisted procreation. Different factors that influence the performance of freezing and thawing of human embryos are reviewed: the data from international and national surveys of results, the cryopreservation procedures, the stages of embryonic development, the morphological appearance of the cryopreserved embryos, the numbers of embryos transferred, the storage times of embryos in liquid nitrogen, the ovarian stimulation protocols in the IVF cycle and the replacement cycles of cryopreserved embryos. Cryopreservation of embryos circumvents the difficult problem of synchrony between the ovarian cycles of donor and acceptor patients in an oocyte donation programme. PMID- 1424328 TI - Viability of preimplantation embryos. AB - Only about 10% of embryos obtained after in vitro fertilization (IVF) are able to implant after transfer in utero. Detecting the viable embryos is therefore the prerequisite condition to increase the overall efficiency of the technique. Zygote and embryo morphology is partly related to their viability. Indeed, fertilized oocytes with a timely fertilization and pronuclear growth, leading to embryos with equally sized blastomeres reaching at least the 4-cell stage about 42 h after insemination, have the best chance of implanting. The metabolic approach, although requiring sensitive microassays, seems promising. Indeed, in a small series 100% of the pregnancies were predicted when the level of interleukin 1-alpha was > 60 pg/ml and the suppressive level (antiproliferative activity using tumour cell lines) was > 20% in the supernatant of transferred embryos. Lastly, invasive assessment of the chromosome status of embryos should allow us in future to discard severely abnormal embryos, thus increasing the success rate of IVF. PMID- 1424329 TI - Gamete intrauterine transfer. AB - Gamete intrauterine transfer has been performed at a very limited scale until now. The main target group of patients for such a treatment would be women with infertility due to the tubal factor, but other infertile patients could benefit also, as the procedures reduce incubation time in the laboratory and implies fertilization in vivo. Few studies have been reported from 1982 to 1990 on the transfer of oocytes and spermatozoa directly to the uterus, and only five clinical pregnancies have been achieved. Transfer of oocytes and spermatozoa inside a biodegradable capsule has only been performed in one study comprising 26 cycles with no ensuing pregnancies. A critical evaluation and a status is carried out. PMID- 1424330 TI - The implantation window. AB - The implantation window is defined as that period when the uterus is receptive for implantation of the free-lying blastocyst. This period of receptivity is short and results from the programmed sequence of the action of oestrogen and progesterone on the endometrium. Implantation itself is a process that commences with apposition, continues through attachment to trophoblast outgrowth and decidualization. For maximal effectiveness of assisted reproductive technologies in women, it is important to know the optimal time for embryo transfer which implies a need to predict the period of uterine receptivity. At present there are no good markers of, or for prediction of, uterine receptivity. In cycles where endogenous hormonal activity is suppressed or absent, the optimal time for embryo transfer can be easily defined and lies between luteal days +3 to +5, where luteal day +1 is the first day of exogenous progesterone treatment. In the human, it is suggested that blastocyst apposition begins about LH day +6 and is complete by LH +10. Human embryos survive in vitro manipulation well, and the stage of development at which they are placed in the uterus seems less critical than in other species, provided they are at an earlier stage of development than that of the endometrium. PMID- 1424331 TI - Indications and outcomes of assisted reproduction. AB - Since 1978 many healthy children have been born after in vitro fertilization and embryo transfer, fulfilling the wishes of many previously childless couples. In vitro fertilization and subsequently developed methods (GIFT, intratubal embryo transfer) have contributed to progress in the diagnosis and treatment of unwanted childlessness. Furthermore these techniques have improved knowledge of ovarian function, fertilization and early embryo development. PMID- 1424332 TI - [Movement-related cortical potential in patients with cerebellar dentate degeneration]. AB - We reported movement-related cortical potentials (MRCPs) in 11 patients with lesion of the dentate nucleus (Machado-Joseph disease (MJD) 7 cases, dentato rubro-pallido-luysian atrophy (DRPLA)1, myoclonus epilepsy associated with ragged red fibers (MERRF)1, dyssynergia cerebellaris myoclonica (DCM) 2), and compared with those of 7 cases of multiple system atrophy (MSA) who were postulated to have mild dentate lesions (striato-nigral degeneration 2 cases, Shy-Drager syndrome 2, sporadic olivo-ponto-cerebellar atrophy 3), and 7 control subjects without any neurological findings. Further we classified the diseases into the following two groups based on the lesion of the dentate nucleus. One was MJD group that had normal or slightly abnormal electroencephalogram (EEG), and the other was DN group (DRPLA, MERRF, DCM) that had markedly abnormal EEG. One of the main findings from this study was smaller slope of the Ns' in the MJD and DN group and normal slope of BP. There was no significant difference in the slope of Ns' between MJD patients and DN patients. This result shows EEG abnormalities have no influence on MRCP recordings. These results suggest that Ns' component may reflect the function in the cerebellar dentate nucleus, and that MRCP is a useful diagnostic method in patients with cerebellar ataxia. PMID- 1424333 TI - [Central nervous system disorders in myotonic dystrophy--with special reference to neuron-specific enolase, S-100b protein and creatine kinase BB isoenzyme levels in CSF]. AB - In order to evaluate central nervous system disorders in myotonic dystrophy (MyD), neuron-specific enolase (NSE), S-100b protein and creatine kinase BB (CK BB) isoenzyme were measured using enzyme immunoassay in MyD. Intelligence quotient (IQ) test (WAIS, 17 cases), electro-encephalography (17 cases) and brain computed tomography (18 cases) were examined. In patients with MyD, NSE level was significantly elevated in comparison with 25 age-sex matched control subjects. In some cases of MyD levels of S-100b protein and CK-BB in CSF were elevated. IQ test disclosed intellectual impairment in 70.6% of the patients examined and EEG study demonstrated slowing of basic rhythm in the majority of the cases. On brain CT both enlarged ventricles and dilated sulci were commonly found. The results of the present study suggest that in MyD the CNS is involved not only functionally but structurally as well. Since NSE, S-100b and CK-BB are localized in neuronal and glia cells, their elevated levels in CSF indicate existence of organic lesions in the central nervous tissue in patients with MyD. PMID- 1424334 TI - [The role of interleukin-6 in Crow-Fukase syndrome]. AB - We measured serum interleukin-6 (IL-6) levels in 14 patients with Crow-Fukase syndrome. Five out of 14 patients with Crow-Fukase syndrome showed high serum IL 6 levels above 10 pg/ml, which was statistically significant in comparison with control subjects with other neurological diseases. Serial studies of serum IL-6 levels in two patients revealed the increase before the exacerbation of clinical symptoms of edema, and pleural or cardiac effusion, and the fall after the treatment by high dose pulsed methylprednisolone. We suggest that serum IL-6 level appears to be a useful marker to predict its exacerbation. Also we performed immunohistochemical study on cutaneous angioma from three Crow-Fukase syndrome patients using anti-IL-6 antibody. The cytoplasm of endothelial cells of cutaneous angioma from two patients was positively stained, which might imply the abnormality of endothelial cells in Crow-Fukase syndrome. PMID- 1424335 TI - [Central nervous system disorders in patients with myotonic dystrophy--in relation to respiratory dysfunction]. AB - Although central nervous system (CNS) involvement, such as intellectual impairment simulating dementia, in myotonic dystrophy (MyD) has been well documented, the cause of this condition remains unclear. In has been reported that the progressive cases of MyD are often accompanied with respiratory disturbance and sleep apnea syndrome (SAS). We studied the relation between CNS involvement and respiratory disorders in 15 MyD patients. They consisted of 10 males and 5 females with ages ranging from 21 to 58 years (average 46 +/- 8.4 years old). Arterial blood gas (ABG) analysis, respiratory function test, and monitoring of arterial oxygen saturation (SaO2) during sleep were carried out. In some cases abnormal respiration during sleep was analyzed with polysomnography. For an assessment of CNS involvement the following examinations were performed; intelligence quotient (WAIS-IQ); electroencephalography (EEG); brain computed tomography (CT); and cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE), S-100b and creatine kinase BB isoenzyme (CK-BB) which were estimated by using enzyme immunoassay. ABG analysis demonstrated the presence of hypercapnia (PaCO2 > 45 torr) during wakefulness in MyD patients. During sleep 14 of the 15 patients showed frequent desaturation phenomenon (SaO2 < 90%), indicating the episodic hypoxemia. Polysomnographic study revealed the occurrence of SAS of both obstructive and central types in all the cases examined. IQ test disclosed intellectual impairment in 80% of the 15 patients, and EEG showed slowing of basic rhythm in the majority of the cases. On brain CT both enlarged ventricles and dilated sulci were commonly observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424336 TI - [Alteration of atrial natriuretic peptide in progressive muscular dystrophy with congestive heart failure]. AB - We measured plasma levels of atrial natriuretic peptide (ANP) in 9 patients of Duchenne muscular dystrophy (DMD) and 3 patients of Becker muscular dystrophy with congestive heart failure (CHF). Administration of digitalis, catecholamine and angiotensin converting enzyme inhibitor resulted in decrease of ANP levels as well as improvement of clinical symptoms of CHF and cardiomegaly. Four DMD patients whose ANP levels were more than 200 pg/ml after the treatment of CHF showed poor prognosis. These results suggest that ANP is a useful marker for the treatment of CHF in progressive muscular dystrophy. PMID- 1424337 TI - [Clinical and neuroradiological studies on orbital myositis and Tolosa-Hunt syndrome]. AB - Tolosa-Hunt syndrome and orbital myositis have common features such as ocular pain, ophthalmoplegia and exophthalmos. Both syndromes are thought to be caused by a granulomatous inflammation involving the cavernous sinus area in the former and the orbital cavity in the latter. The question whether these two conditions represent different presentations of a single disease, or they belong to different entities has not been settled. To address this question, we reviewed our cases having clinical diagnosis of either Tolosa-Hunt syndrome or orbital myositis. Six cases were diagnosed as Tolosa-Hunt syndrome, and 7 orbital myositis. In the thin-slice enlarged orbital CT, hypertrophic and high-density changes of at least one of the extraocular muscles were found in all cases with orbital myositis, but in none of the patients with Tolosa-Hunt syndrome. The age of onset was younger and the duration of the disease before admission was shorter in Tolosa-Hunt syndrome. They responded to steroid therapy better than those with orbital myositis. These findings lead us to conclude that Tolosa-Hunt syndrome and orbital myositis belong to different syndromes, although clinical manifestations have many similarities. Then we studied the relationship between the hypertrophic change of the extraocular muscle and the direction of the oculomotor restriction. For this purpose four additional cases with dysthyroid ophthalmopathy were also studied. We found that the presence of hypertrophic change was frequently associated with the restriction of ocular movement to the direction not only of the hypertrophic muscle but also of the opposite muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424338 TI - [A case of adrenoleukodystrophy having progressed from the frontal lobes]. AB - A 12-year-old boy was admitted to our hospital in May 1990. Since two years previously, he became restless and could not adapt himself to his new school mates and teacher. He came to refuse going to school, and his intellectual performance rapidly deteriorated, thereafter. During the following two years, he gradually became mutic and incontinent with dystonic involuntary movements, and was admitted to our hospital. Examination revealed melanoderma, mutism, dementia and grossly normal visual and auditory system except for bilateral optic atrophy. Volitional movements were severely limited because of marked truncal and extreme dystonia and spastic paresis. Urinary 17-KS and 17-OHCS were decreased. Serum cortisol did not increase normally on rapid ACTH test. Very-long-chain fatty acids in serum were increased. Serial CTs and MRI demonstrated marked ventricular dilatation and diffuse white-matter lesions involving the frontal lobes, corpus callosum, internal capsules, and less markedly parieto-occipital regions with slight calcification in the optic radiations. Those in the frontal lobes had been visualised in CTs taken 18 months after the onset. School refusal, the initial symptoms of the patient, is one of serious socioeducational problems in Japan. While the majority of children with school refusal might be of non-organic affections, those with apparent mental deterioration and behavioral abnormalities should undergo non-invasive CT or MRI evaluation during the early stage of the disorder. And if diffuse white matter lesions is suggested even in the frontal lobe, the possibility of adrenoleuko-dystrophy should be considered. PMID- 1424339 TI - [A case of progressive supranuclear palsy dramatically improved with L-threo-3,4 dihydroxyphenylserine]. AB - We report a 67-year-old female with progressive supranuclear palsy (PSP) who dramatically improved when given L-threo-3,4-dihydroxyphenylserine (L-DOPS). This patient developed dysarthria, lack of facial expression, and slowness at age 64. She was admitted to a local hospital, diagnosed as having parkinsonism and treated with antiparkinsonian drugs. Despite this treatment, she had difficulty in turning over in bed and standing up from a seat, and began to fall backward at age 65. One year later, she had trouble in walking due to frequent falls and became bedridden. The patient was admitted to our hospital in July 1991 under treatment with 20 mg/200 mg of carbidopa/L-dopa and 4 mg of trihexyphenydyl hydrochloride per day. Neurological examination revealed masked face, pseudobulbar palsy, and dystonic rigidity of the neck and upper trunk. Eye movements were normal except for impaired vertical saccades and convergence inability. Deep tendon reflexes were generally brisk and the plantar responses were flexor bilaterally. Tests of pulsion showed that her postural reflex was markedly disturbed, especially in retropulsion. Her gait showed severe unsteadiness. Neuropsychological tests showed intellectual impairment, frontal lobe dysfunction, and memory disturbance. Computed tomography showed an atrophic midbrain with prominent enlargement of ambient and quadrigeminal plate cisterns. Single photon emission computed tomography (SPECT) using 123-I-isopropyl iodoamphetamine demonstrated marked frontal hypoperfusion. L-DOPS was administered at a dose of 100 mg per day and gradually increased up to 600 mg per day over a period of five weeks, while carbidopa/L-dopa and trihexyphenidyl hydrochloride were continued as on admission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424340 TI - [A case of "syndrome of progressive muscle spasm, alopecia, and diarrhea (Satoyoshi)" treated with steroid pulse therapy]. AB - A 20-year-old man was admitted to our hospital because of generalized muscle cramp with pain. At the age of 12 years, he began to have painful muscle cramps in calf muscles, which gradually extended to all limb and truncal muscles and became more severe and frequent. He also had diarrhea and mild hair loss. On admission he had mild baldness, left shoulder deformity, and hypertrophic muscles. Muscle cramps were observed especially in the extremities. Routine laboratory studies revealed moderately high serum CK and low IgG levels. He had been treated with several muscle relaxants and antiepileptic drugs, but with no favorable effect. During his admission he received high-dose intravenous methylprednisone of 1000 mg/day for three days, followed by oral prednisolone tapered over 4 weeks. Soon after the initiation of the treatment, painful muscle cramps were gradually decreased and his activity of daily life apparently improved. In conclusion steroid pulse therapy is a useful treatment for patients who are not responsive to dantrolene sodium administration, and the effectiveness suggests that a certain autoimmune mechanism plays a role in pathogenetic mechanism. PMID- 1424341 TI - [Chronic inflammatory demyelinating polyneuropathy--an electrophysiological and histological study of the ulnar nerve from a case with intractable persistent conduction block]. AB - We report a 71-year-old male with CIDP, in whom complete motor conduction block persisted for more than several years. Corticosteroid and plasma therapy showed little effect to his weakness. He died of pneumonia. The ulnar nerve in which complete conduction block had persisted was taken out immediately after death and studied with conventional histological and morphometrical techniques. In the transverse section, many thinly-myelinated fibers and some cluster formations were confirmed. Active axonal degeneration was scarce. Myelinated fiber density was 7,417/sgmm. Fiber diameter histogram showed a two-peaked normal distribution. It is thus concluded that demyelination with little axonal degeneration can be the main pathological process causing intractable weakness and poor prognosis of CIDP. Low CMAPs should not lead to therapeutic nihilism, because it may simply be caused by demyelination without exonal degeneration in CIDP. PMID- 1424342 TI - [Necrotic plaque formation in a case of frontal lobe multiple sclerosis]. AB - We reported an unusual case of multiple sclerosis (MS), clinical manifestations and neuroimagings of which were restricted to the frontal lobes and Gd-enhancing plaques on MRI later changed to necrotic lesions. A 36-year-old previously healthy man developed behavioral changes without any other neurological manifestations in a few weeks. Findings of magnetic resonance imaging (MRI) together with visual evoked potentials pointed to MS and corticosteroid pulse dose therapy was initiated. Despite fairly uneventful, but rather delayed clinical recovery, repeated MRI disclosed rows of multiple, periventricular plaques localized to the bilateral frontal white matter and indicated the majority of lesions were not those of demyelination but necrosis. Frontal lobe syndrome is rarely encountered as a sole manifestation and rates only a few percent of MS cases in the literature. We speculated on the pathogenesis of necrotic plaques in this particular case; tumor necrosis factor, interleukin-1 and other cytokines that are known to be accompaniments of inflammatory cell infiltrates and activated glia in MS may ultimately destroy the CNS tissue, if the inflammation is not readily controlled. It is not certain, however, that what are determinants of demyelination and what drives further to the devastating tissue necrosis. Despite the uncertainty, this case indicates a necessity of immediate institution of adequate immunosuppressive therapy when neuroimaging study indicates active inflammation and openings of the blood-brain barrier in demyelinating plaques. PMID- 1424343 TI - [Unusual pathological ocular movement caused by dysfunction of the saccade generation mechanism]. AB - We describe a patient with abnormal ocular movement, probably due to dysfunction of saccade generation mechanism in the lower pons involving the omnipause neuron and a feed-back circuit. A 26-year-old man had fever, mild headache and sore throat for a few days and also noted unstable gait and diplopia. These symptoms subsided, but he noticed oscillopsia about 2 months later. On admission in our hospital, the neurological examination revealed no abnormalities except for abnormal eye movements, which were induced by voluntary or involuntary ocular movement and lasted for a few minutes. The abnormal ocular movement was irregular in direction, amplitude and rhythmicity, and the voluntary and involuntary ocular movements could not be elicited during the period of this abnormal ocular movement. The abnormal ocular movement completely disappeared for about 1 hour by intravenous injection of TRH. At this time bilateral mild abducens palsy was demonstrated by EOG examination. The abnormal ocular movement in this patient, which has nerve been reported in the literature, was considered to be due to a disinhibition of excitatory burst neuron (EBN) caused by the dysfunction of omnipause neuron, and possibly due to a delay of feed-back information of saccade to the EBN. PMID- 1424344 TI - [Spinal cord sarcoidosis--diagnostic value of Gd-enhanced MRI]. AB - A 50-year-old man was admitted because of slowly progressive myelopathy for the last ten months without a correct diagnosis. The CSF showed mild pleocytosis (predominantly mononuclear cells) together with elevated protein content. MRI findings after administration of Gd-DTPA were characteristic: diffuse swelling of the lower cervical and upper thoracic cord, multiple patchy enhanced areas in the cord parenchyma adjacent to meninges, and linear meningeal enhancement. Based on these observations, a scalene node biopsy was performed, yielding a pathological diagnosis of sarcoidosis. The clinical neurological signs as well as the abnormal MRI findings of myelopathy were considerably improved after prednisolone therapy. An early diagnosis of spinal cord involvement in sarcoidosis should be established, because it is treatable in the earlier stage. Mild inflammatory evidence in CSF and Gd-enhanced MRI findings may be the cardinal clues to the diagnosis. PMID- 1424345 TI - [Botulinum toxin trial for spasticity]. AB - We treated three patients with spastic paraparesis with botulinum toxin (BTX). Two of them had scissors gait reflecting the hypertonus of adductors. In both, an injection of BTX to the responsible muscles improved gait, albeit transiently. The effect was shortlived, probably because increased tonus in non-injected portions compensated for the weakness of injected portions. In the third patient with no abnormality in tonus of the adductors, BTX injection in quadriceps caused a weakness with exacerbation of gait disturbance. We concluded that, in selected cases, BTX therapy is useful for spastic paraparesis to alleviate hypertonicity of the adductors. PMID- 1424346 TI - [Transverse myelopathy in a patient with systemic lupus erythematosus associated with positive anticardiolipin antibody--a case report]. AB - A 52-year-old woman who developed acute transverse myelopathy following systemic lupus erythematosus (SLE) was reported. At the age of 46, she was diagnosed as having atypical psychosis. Neurological examination revealed mild depressive state, paraparesis, diffuse hyperreflexia, hypesthesia below the breasts, and urinary disturbance. Gait was slightly ataxic and Romberg sign was positive. Laboratory study disclosed lymphocytopenia, positive antinuclear antigen, false positive Venereal Disease Research Laboratories flocculation test and prolonged activated partial thromboplastin time. IgG anticardiolipin antibody (aCLA) was positive, whereas IgM aCLA was negative. Cerebrospinal fluid was normal except the elevation of %IgG. Nerve conduction studies were normal and no abnormality was detected in the brain and spinal cord by MRI and CT. We treated her by two series of steroid pulse therapy, which resulted in marked improvement of symptoms and disappearance of aCLA. Before and after the pulse therapy, symptoms were fluctuated in parallel with the levels of aCLA. These findings suggest the relation of aCLA to the transverse myelopathy in SLE. This is the first case report of a good prognosis of myelopathy in a SLE patient who was treated by steroid pulse therapy with the aim of disappearance of aCLA. PMID- 1424347 TI - [Chlamydia trachomatis infection with symptoms and signs of the central nervous system damage--a case report]. AB - A 32-year-old woman developed myalgia, fever, consciousness disturbance, mental disorder, pyramidal tract signs and meningeal irritation signs at about 2 months after a normal labor. Laboratory examination showed hypopituitarism (decreased ACTH, TSH), renal dysfunction and hypercalcemia. A variety of antibiotics, acyclovir and gamma-globulin failed to improve her symptoms. A diagnosis of Chlamydia trachomatis infection was considered from the elevated antibody titers. In this case, minocycline was very effective. Rarely Chlamydia trachomatis infection involved general organs, including the central nervous system. It was interesting that she had endocrine disorders. We must take a look for Chlamydia trachomatis infection because this infection infrequently involves general organs, including the central nervous system and minocycline is very effective for this infection. PMID- 1424348 TI - [Strongly succinate dehydrogenase-reactive blood vessels (SSV) in various neuromuscular diseases]. AB - The strongly succinate dehydrogenase-reactive blood vessels (SSV) are shown to have increased numbers of enlarged mitochondria in smooth muscle cells of the vessel wall on electron microscopy. They are seen in biopsied skeletal muscles from patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) at high frequency. The present study was done to examine the incidence of SSV in biopsied muscles from various neuromuscular diseases. Among 107 patients with mitochondrial encephalomyopathies (MEM) including 50 with chronic progressive external ophthalmoplegia (CPEO), 7 with myoclonus epilepsy with ragged-red fibers (MERRF), and 50 with MELAS, SSV were seen in nearly a half of the patients, and comprised approximately 24% of small arteries. On the other hand, SSV in 100 patients with various neuromuscular diseases other than MEM were exceptional, and only one of 8 patients with myotonic dystrophy had SSV. These findings suggest that the SSV are induced by functional abnormality of mitochondria in smooth muscle cells, and that an identification of the SSV is an additional crucial evidence to make a pathological diagnosis of MEM. PMID- 1424349 TI - [Surface anatomy scanning image by MRI in herpes simplex encephalitis]. AB - We present surface anatomy scanning (SAS) image by weighted-summation technique using MRI images in herpes simplex encephalitis. Recently, SAS has been developed as a technique that visualizes brain surface structures. This patient was a 64 year-old male who suffered from aphasia and memory disturbance after herpes simplex encephalitis. He was transferred to our hospital for rehabilitation. Neuropsychological tests showed Wernicke's aphasia and memory impairment. SAS was performed for the purpose of analyzing these neuropsychological deficits, especially the Wernicke's aphasia. In SAS image, sulci were enhanced and gyri were easy to identify clearly. The affected structures disclosed low intensity areas in the entire left temporal lobe, including the superior temporal gyrus. It was clarified that the damage to the left superior temporal gyrus resulted in his Wernicke's aphasia. We think that SAS is very useful for cortical lesion analysis, not only in encephalitis but also in other disorders presenting higher brain dysfunctions. PMID- 1424350 TI - Laparoscopic versus conventional cholecystectomy. Use of biliary scintigraphy. AB - Laparoscopic cholecystectomy has become a popular alternative to traditional open cholecystectomy for uncomplicated, acute cholecystitis. At some centers, laparoscopic cholecystectomy is already the more frequently performed procedure. The presence or suspicion of common bile duct (CBD) stones or obstruction may necessitate conventional surgery or additional procedures. This report describes a patient with acute cholecystitis for whom the surgical management changed based on biliary scintigraphy. The demonstration of an unsuspected CBD obstruction by biliary imaging allowed the surgeon to change the initial plan for laparoscopic cholecystectomy to conventional open surgery. Stones in the common bile duct were removed. PMID- 1424351 TI - Comparison of gallbladder ejection fraction with histopathologic changes in acalculous biliary disease. AB - This selective retrospective study was undertaken to establish whether the gallbladder contraction (ejection fraction) calculated during cholescintigraphy correlates with the histopathologic changes in the surgical specimen. The medical records of 243 patients who underwent hepatobiliary scintigraphy were reviewed. Of these, 215 patients had cholecystokinin cholescintigraphy and 100 went on to cholecystectomy. The original histologic slides from 67 gallbladders were available and reviewed by a pathologist who graded each specimen based on presence and severity of changes associated with "chronic" cholecystitis. There was no significant correlation between the severity of histopathologic change and cholecystokinin-induced gallbladder emptying. PMID- 1424352 TI - Tc-99m albumin scintigraphy in the localization of protein loss in the gut. AB - Scintigraphic localization of gastrointestinal protein loss has been recently reported. A noninvasive method for the localization of protein loss in the gut using Tc-99m labeled albumin seems encouraging and is described here. In six patients studied for protein-losing enteropathy, scintigraphic results of four were positive. PMID- 1424353 TI - Intraperitoneal bleeding demonstrated by Tc-99m labeled red blood cell scintigraphy. AB - Tc-99m RBC scintigraphy is known to be useful for the evaluation of gastrointestinal bleeding. The authors describe a patient with a posttraumatic peritoneal tap in whom Tc-99m RBC imaging showed bleeding into the gastrointestinal wall and into the ascitic fluid. PMID- 1424354 TI - Combined Ga-67 and In-111 leukocyte scintigraphy to characterize a liver mass in a patient with lymphoma. AB - A 32-year old man with Hodgkin's disease was admitted to the hospital with a liver mass. The primary diagnostic possibilities, infection and lymphoma, require markedly different therapy. The combination of Ga-67 and In-111 white blood cell imaging correctly diagnosed the mass as lymphoma. PMID- 1424355 TI - Occult aortic arch mycotic aneurysm diagnosed by radiogallium scintigraphy. AB - Aortic arch mycotic aneurysm, an uncommon cause of sepsis, carries a grave prognosis. Clinical presentations as well as laboratory and radiologic examinations may be noncontributory and often misleading. In a patient with a fever of unknown origin, only the radiogallium study could enable an accurate diagnosis and pinpoint the anatomic localization of the mycotic aneurysm as the cause of fever. PMID- 1424356 TI - Brain SPECT imaging in progressive aphasia. AB - Progressive aphasia without dementia is a relatively uncommon neurobehavioral syndrome. The initial presentation of progressive aphasia without cognitive impairment may pose a diagnostic dilemma. The authors report a patient with progressive aphasia. The initial neuro-imaging studies (MRI, CT) were not diagnostically helpful. However, brain SPECT imaging with Tc-99m HMPAO clearly demonstrated a left temporal lobe abnormality. This report discusses the potential clinical usefulness of brain SPECT imaging in the evaluation of neurobehavioral disorders. PMID- 1424357 TI - Ga-67 citrate accumulation in adenomatous goiter. AB - An elderly woman with a diffusely enlarged goiter and multiple miliary nodular lesions on chest x-ray showed Ga-67 accumulation in the right thyroid lobe. Histologic findings obtained after total thyroidectomy and open lung biopsy revealed papillary carcinoma in the left lobe with pulmonary metastases and adenomatous nodules in the right lobe. This is the first report of Ga-67 accumulation in adenomatous goiter. PMID- 1424358 TI - Early and delayed imaging of Tc-99m HMPAO versus Tl-201 in benign and malignant thyroid tumors. Similar uptake but different retention. AB - The authors performed both Tc-99m HMPAO and Tl-201 scintigraphy in 30 patients with thyroid tumors (21 papillary adenocarcinoma, three solid follicular adenoma, six adenomatous goiter with cystic degeneration). Increased accumulation of both Tc-99m HMPAO and Tl-201 was seen in 14 patients with papillary adenocarcinoma and three with solid follicular adenoma, whereas two patients with papillar adenocarcinoma had low accumulation of both tracers. Of the six patients with adenomatous goiter with cystic degeneration, four had low accumulation of both Tc 99m HMPAO and Tl-201, and one patient had low accumulation of Tc-99m HMPAO only. Iso accumulation (same accumulation as the normal thyroid) of Tc-99m HMPAO was seen in five patients with papillary adenocarcinoma and one with adenomatous goiter. The distribution of Tc-99m HMPAO in the thyroid tumors and normal thyroid tissue was independent of time from 2 to 120 minutes after injection. The results of dynamic studies using Tc-99m HMPAO suggested that the accumulation of Tc-99m HMPAO in thyroid tumors reflected mainly tumor blood flow. The resultant Tc-99m HMPAO images were essentially similar to the Tl-201 images obtained 10 minutes after injection. Tc-99m HMPAO imaging can be a suitable substitute for Tl-201 imaging, and it may possibly be used to estimate tumor blood flow in patients with thyroid tumors. PMID- 1424359 TI - Localization of Tc-99m DTPA in a chordoma. AB - The authors report a patient with chordoma that was demonstrated as a photopenic region on Tc-99m MDP bone imaging but that localized Tc-99m DTPA intensely. An explanation for the discrepancy is discussed. Complementary Tc-99m DTPA imaging in the preoperative evaluation of sacral tumors is suggested. PMID- 1424360 TI - Fracture of the laryngeal cartilage. An incidental finding on bone scintigraphy. AB - A patient complaining of headaches and bone pain at multiple sites had Tc-99m MDP scintigraphy performed for possible bone trauma after a motor vehicle accident. Bone imaging revealed a small focal increase in tracer uptake in the area of the laryngeal cartilage. There was some reluctance to place a label on this abnormality because the findings were so unusual. The initial diagnosis was a probable fracture of the laryngeal cartilage. Computed tomography of the neck also demonstrated a fracture but correctly localized it to the thyroid cartilage. PMID- 1424361 TI - Lung perfusion imaging in electromechanical dissociation from massive pulmonary embolization. PMID- 1424362 TI - Tc-99m MIBI uptake in the sternum. PMID- 1424364 TI - Splenic infarction. Detection by In-111 leukocyte scintigraphy. PMID- 1424363 TI - Seemingly isolated hepatic tissue. PMID- 1424365 TI - Lyme carditis. Evaluation by Ga-67 and MRI. PMID- 1424366 TI - Scintigraphic pitfall in a patient with steatopygia. PMID- 1424367 TI - Accumulation of In-111 labeled white blood cells in a wound dressing. A potential cause of false-positive results. PMID- 1424368 TI - Potential false-positive urinary leak from vesico-duodenal reflux in a combined renal-pancreatic transplant. PMID- 1424369 TI - Gallstone simulating renal lesion on skeletal scintigraphy. PMID- 1424370 TI - Bilateral ectopic pelvic kidneys incidentally demonstrated by radioisotope angiography. PMID- 1424371 TI - Detection of renal artery stenosis by means of captopril renal scintigraphy in patients with multiple renal arteries. AB - Both captopril renal scintigraphy (CRS) and conventional arteriography were retrospectively evaluated in 64 patients to study CRS efficacy in hypertensive patients with multiple renal arteries (MRA). The presence of MRA was angiographically demonstrated in 9 patients, 7 unilaterally and 2 bilaterally, with a total of 11 kidneys supplied by 2 or more arteries. Overall, 25 MRA were identified and 7 were affected by stenosis of > 50%, causing a reduction of arterial supply in 5 of 11 kidneys. CRS correctly diagnosed all five ischemic kidneys (true positives) and five of six nonischemic kidneys (true negatives); in one case in which perfusion was not reduced, the CRS diagnosis was falsely positive. In the presence of MRA, CRS proved effective in identifying renal artery stenosis of > 50%, involving either one or all the MRA. This study shows that the presence of MRA is not a drawback in the evaluation of renal artery stenosis by means of CRS. PMID- 1424372 TI - Ga-67 lung uptake in patients with adult respiratory distress syndrome. Association with lung infection and patients' prognosis. AB - Nine patients with adult respiratory distress syndrome (ARDS) were studied with Ga-67 imaging in search for a site of infection. Different degrees and two patterns of Ga-67 lung uptake scoring in comparison with liver uptake were demonstrated. All patients had diffuse lung uptake, whereas five of them also showed additional focal lung activity. In only one patient was an abdominal focal uptake detected. Chest radiographs of all patients revealed diffuse and focal lung infiltrates that correlated with the Ga-67 uptake patterns. Therefore, Ga-67 imaging was unhelpful in differentiating patients with ARDS with lung infection from patients without lung infection. The intensity of Ga-67 uptake, as expressed by Ga-67 scoring, correlated with the course and outcome of ARDS. Patients exhibiting a high Ga-67 score had long periods of hospitalization and eventually died (four patients), whereas those who had low Ga-67 scores had a short disease course and survived (five patients). It is concluded that Ga-67 imaging in ARDS patients is unable to detect lung infection; however, it may be useful in the assessment of patients' prognosis. PMID- 1424373 TI - Osteitis pubis, Tc-99m MDP, and professional hockey players. AB - Three cases of osteitis pubis detected by bone scanning with Tc-99m MDP in professional ice hockey players are presented. This entity is related to mechanical stress and aggravated by forceful contraction of the adductor and rectus abdominis muscles. The signs, symptoms, and laboratory data are relatively nonspecific, as are radiographic findings in the early stage (pubic symphysitis). The use of bone scanning in the appropriate clinical setting aids in diagnosis. PMID- 1424374 TI - Diffuse liver and splenic activity with Tc-99m MDP associated with iohexol injection. A case report. PMID- 1424375 TI - Portal vein aneurysm demonstrated by blood pool SPECT. AB - Portal vein aneurysms are rare and are occasionally suggested by ultrasound and usually confirmed by invasive angiography. Such a case was diagnosed by scintigraphic studies, most importantly blood pool SPECT, which clearly separates it from hepatic cysts. PMID- 1424376 TI - Pulmonary scintigraphic findings in children with pectus excavatum by the comparison of chest radiograph indices. AB - Pulmonary scintigraphy, including Xe-133 ventilation combined with Tc-99m MAA perfusion scans, was performed in 23 children (3 girls, 20 boys, ages: 2-9 years) with pectus excavatum, and the indices from lateral chest radiography were used for comparison. The findings of pulmonary scintigraphy were analyzed as 1) ventilation fractions (VF), and 2) perfusion fractions (PF) between bilateral lungs; and 3) ventilation-perfusion ratios (V/Q ratio) of both lungs. The results showed that 6 of 23 cases had impaired VF, 11 of 23 cases had impaired PF, and 7 of 23 cases had an impaired V/Q ratio in the right and left lung, respectively. The severity of sternal depression in pectus excavatum was shown as certain indices that were obtained on routine lateral chest radiographs. However, no significant correlations existed between the differences in the fractions and the indices. Our results suggest that pulmonary scintigraphy is not necessary for children with pectus excavatum to predict the severity of sternal depression and pulmonary function, because 1) pulmonary scintigraphy is very difficult to perform in children; 2) unnecessary radiation exposure should be avoided; and 3) it is not well correlated with the severity of the depressed sternum. PMID- 1424377 TI - Regional cerebral blood flow measured with I-123 IMP SPECT in a case of subcortical arteriosclerotic encephalopathy (Binswanger's disease). AB - N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT studies were performed on a 75-year-old patient who could be clinically classified as subcortical arteriosclerotic encephalopathy (Binswanger's disease). Regional cerebral blood flow (rCBF) was quantitatively measured by a microsphere model, and was diffusely decreased in the whole brain (mean rCBF: 36 ml/100 g/minute). After a ventriculoperitoneal shunt operation, his clinical symptoms were markedly improved, and the improvement was validated by a 32% increase of mean rCBF. However, MRI and CT images showed no significant interval changes before and after the shunt operation. Regional rCBF measurement by I-123 IMP SPECT should be performed and plays an important role in the evaluation of Binswanger's disease. PMID- 1424378 TI - Portacaval graft patency demonstrated by scintigraphic calculation of portal contribution to hepatic blood flow. AB - The case presented refers to a cirrhotic patient with portal hypertension in whom a portacaval graft bypass was surgically implanted. The calculation of the portal contribution to hepatic blood flow helped to demonstrate the patency of the graft. PMID- 1424380 TI - Circumflex masquerade. PMID- 1424379 TI - Clinical value of lung scintigraphy with Tc-99m gluconate in distinguishing benign from malignant lung diseases. AB - One hundred patients were studied with three-phase lung scintigraphy with Tc-99m gluconate. The results showed that there were statistically significant differences between benign and malignant lung lesions in the intensity of accumulation, the blood supply index ratio, and the radioactive uptake ratio. However, no difference was observed between the benign lung lesions and the healthy lungs. Analysis of false negatives and false positives revealed that false negatives had something to do with the cell types of the malignancies, in addition to the relatively small size of the lesions; the false positives were mostly caused by acute inflammation, for which obstructive pneumonitis might be responsible in part. It is concluded that Tc-99m gluconate is tumor-avid and can be used as an agent for positive imaging of lung cancer, because quantitative parameters, blood supply index ratio, and radioactive uptake ratio are more objective in distinguishing malignant lung lesions from benign ones, and are of relatively higher sensitivity and specificity. Thus, lung scintigraphy with Tc 99m gluconate provides an efficient supplementary measure for differentiating between malignant and benign lung lesions. PMID- 1424381 TI - Osteoid osteoma involving body of right rib. Preoperative localization and postoperative confirmation. PMID- 1424382 TI - Gallium-67 uptake after breast and hip augmentation with silicone. PMID- 1424383 TI - Extrapulmonary uptake in the spleen during lung perfusion with Tc-99m MAA. PMID- 1424384 TI - Pigmented villonodular synovitis of the knee demonstrated on bone scan. Correlation with US, CT, and MRI. PMID- 1424385 TI - Uptake of in-111 leukocytes in soft tissue metastases from adenocarcinoma of lung. PMID- 1424386 TI - Marine-Lenhart syndrome. Graves' disease with poorly functioning nodules. PMID- 1424387 TI - Uptake of Tc-99m HMDP in an abdominal aortic aneurysm. PMID- 1424389 TI - Incidental finding of pulmonary sarcoidosis during stress thallium imaging. PMID- 1424388 TI - Marked soft tissue uptake of bone tracer in a patient with amyloidosis and multiple myeloma. PMID- 1424390 TI - Incidental identification of hepatic metastasis during gated cardiac imaging. PMID- 1424391 TI - Explanations and therapies for penicillin failure in streptococcal pharyngitis. AB - A disturbing trend toward penicillin failure has developed in the treatment of streptococcal pharyngitis in some parts of the United States and abroad. A variety of explanations has been proposed to account for these penicillin treatment failures. With the resurgence of serious complications from streptococcal infection, successful bacteriologic eradication has regained importance. In communities with a high incidence of penicillin failures, alternative antimicrobials should be considered. Cephalosporins, amoxicillin/clavulanate, and the extended-spectrum macrolides represent logical options under such clinical circumstances. PMID- 1424392 TI - Cholelithiasis in infants with Down syndrome. Three cases and literature review. AB - Only four cases of cholelithiasis have been reported in patients with Down syndrome and none in Down syndrome infants. The cases of three Down syndrome infants (all males) with cholelithiasis are reported. Each exhibited different fetal complications, and in each, Down syndrome was diagnosed at birth. Gallstones apparently were congenital (a rarity) in one infant, since they were detected on the first day of life. Cholelithiasis was an incidental finding in another of the infants when, at 12 weeks old, he had renal ultrasonography because of a urinary tract infection. The third infant was 4 months old when sonographic studies revealed a gallstone. Despite the confirmation of cholelithiasis in all three infants, none has since had any signs or symptoms that suggest the need for intervention. Cholelithiasis is probably more common in Down syndrome infants than has been supposed, but whether Down syndrome infants with gastrointestinal (GI) malformations are more likely to have gallstones than are children with similar GI malformations but with normal karyotypes is unknown. PMID- 1424393 TI - Fractures in the under-3-year-old age cohort. AB - One hundred twenty-four urban children under 3 years of age admitted for fractures were retrospectively reviewed to determine the frequency of accidental and nonaccidental causes in this population. The fractures were categorized according to their mechanisms: motor-vehicle passenger or pedestrian accident, other accidents, or child abuse. There were no differences in the frequency of fractures by race, date of birth, or season in which the injury occurred. Skull fractures were most frequent (62%), followed by femur fractures (11%). There was a 26% increase in fractures between 1987 and 1989, especially in the non-motor vehicle cohort. Caretaker ignorance and/or carelessness was a common cause of fractures in the infant and toddler age group. Injuries were still occurring in spite of infant care seat use. The American public must be educated in preventive medicine and safety to decrease the senseless morbidity of our greatest resource. PMID- 1424394 TI - Screening for psychosocial dysfunction in pediatric practice. A naturalistic study of the Pediatric Symptom Checklist. AB - This study examined the routine implementation of the Pediatric Symptom Checklist (PSC), a brief questionnaire which screens for psychosocial dysfunction in school aged children in an outpatient pediatric practice. Results indicated that the PSC was well-accepted by parents and adequately tolerated by busy clinic staff. When the PSC was included as part of the standard procedure for well-child visits, the referral rate for psychosocial problems due to positive PSC scores rose to 12% from the clinic baseline referral rate of 1.5%, a significant increase (P < .01). Half of the children who screened positive on the PSC had not been previously identified by their pediatricians as having psychosocial problems, and more than half had never received any psychological treatment. When implementation of the PSC was discontinued, the referral rate fell to 2%, a rate similar to baseline. The findings suggest that it is possible to incorporate the PSC into routine pediatric practice and that the PSC can help pediatricians identify and better serve children experiencing psychosocial difficulties. The study also suggests that further work is needed to understand the barriers to ongoing implementation. PMID- 1424395 TI - Regional anesthesia in the preterm neonate. AB - The physiologic immaturity of respiratory musculature and central respiratory control centers leads to an increased risk of apnea and respiratory complications following general anesthesia in the neonate. Regional anesthetic techniques, such as spinal and caudal epidural anesthesia, may obviate the need for general anesthesia and lessen the risks of perioperative morbidity. Although these techniques have been previously described in infants, most reports focus on regional anesthesia in the former preterm infant outside the actual neonatal period. There is relatively little or no information concerning regional anesthesia in neonates during the first week of life. We present four neonates (weight, 1.07 to 2.8 kg; gestational age, 27 to 35 weeks) who required anesthetic care during the first week of life for various surgical procedures, including vesicostomy placement, gastroschisis closure, and debridement of a lower extremity wound. Either caudal epidural or spinal anesthesia was successfully used in the four neonates. Regional anesthesia was used as the sole technique without supplementation with intravenous or inhalational agents in three of the four neonates. The advantages, risks, and applications of regional anesthesia in the neonate are discussed. PMID- 1424397 TI - Behavioral aspects of asthma in children. PMID- 1424396 TI - Taking it to the streets. Helmet use and bicycle safety as components of inner city youth development. AB - A three-week bicycle safety module (BSM) featuring helmet use was developed for an inner-city, comprehensive youth development program in East Wheeling, West Virginia. Prior to BSM intervention, no helmet use had been observed in the test neighborhood. After a three-week program focusing on safety behaviors and helmet use, students demonstrated significant improvements in knowledge, a positive relationship between skill and knowledge, and nearly 100 percent helmet usage rates. Unfortunately, neighborhood helmet use rates fell to nearly zero after the summer camp was over. The data suggest that helmet use and improved knowledge and skills could become the norm in an inner-city day-camp context, but periodic, model-oriented reinforcement of the BSM is recommended for maintenance of observed knowledge and usage improvements. PMID- 1424398 TI - Diabetes in cystic fibrosis. PMID- 1424399 TI - Respiratory syncytial virus infections. PMID- 1424400 TI - Choreiform movements observed in an 8-year-old child following use of an oral theophylline preparation. PMID- 1424401 TI - Hypocalcemia in nonwhite breast-fed infants. Vitamin D deficiency revisited. PMID- 1424402 TI - Leuconostoc species bacteremia in a child with acquired immunodeficiency syndrome. PMID- 1424403 TI - Albuterol dosage and acute asthma. PMID- 1424404 TI - A question on nail-biting. PMID- 1424405 TI - HIV status in varicella pneumonia. PMID- 1424406 TI - Protein-losing enteropathy associated with rubella. PMID- 1424407 TI - Pharmacokinetics and pharmacodynamics of intravenous meperidine in neonates and infants. AB - The pharmacokinetics of meperidine (pethidine) was studied in 21 infants who received a single intravenous dose of 1 mg/kg after surgery (n = 18) or during mechanical ventilation because of respiratory distress (n = 3). Eleven patients were younger than 1 week old, 10 patients were aged from 3 weeks to 5 months, and five of the patients were premature. The pharmacokinetics of meperidine varied greatly between the subjects, with a median elimination half-life of 10.7 hours (range, 3.3 to 59.4 hours), median clearance of 8.0 ml/kg/min (range, 1.8 to 34.9 ml/kg/min), median volume of the central compartment of 2.4 L/kg (range, 0.5 to 4.8 L/kg), and median steady-state volume of distribution 7.2 L/kg (range, 3.3 to 11.0). The great interindividual variability in meperidine pharmacokinetics should be taken into consideration when meperidine is administered to neonates. Although no life-threatening or serious side effects were observed in this study, appropriate care should be exercised when prescribing meperidine for this age group. PMID- 1424409 TI - Classic conditioning and placebo effects in crossover studies. AB - OBJECTIVE: To find evidence of classically conditioned placebo effects in a placebo-controlled crossover drug study. Specifically, we tested a prediction of the conditioning model that the placebo response will be greater after drug exposure than before. METHODS: Twenty-four patients with mild to moderate essential hypertension and no contraindications to atenolol participated in the study. The study design required randomized assignment to one of three groups: placebo followed by 50 mg atenolol daily, followed by no treatment, each for 1 week; atenolol followed by placebo; and atenolol followed by nothing (to show residual drug effects). Twice-daily blood pressure measurements were made by patients at home; once-weekly measurements of blood pressure and heart rate were made by a research nurse. RESULTS: Before drug treatment, there were no differences in the antihypertensive responses of patients taking placebo and patients taking nothing (difference, 0.98 mm Hg; 95% confidence interval, -0.98 to 2.93). After atenolol treatment, placebo treatment produced a significantly greater antihypertensive response than no treatment (difference, -6.09 mm Hg; 95% confidence interval, -11.81 to -0.38). Thus the placebo response after atenolol administration was more than a residual drug effect. Similar patterns were observed for heart rate but not for blood pressure readings taken in the office. CONCLUSIONS: These observations are consistent with a conditioning model of placebo effects. These findings warrant further investigation in larger studies and in other disease models. PMID- 1424408 TI - Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. AB - In 26 hospitalized patients with depression, a combined pharmacogenetic test with dextromethorphan, a substrate of cytochrome P450IID6, and mephenytoin, the S-form of which is hydroxylated by a P450IIC isozyme, was carried out before amitriptyline therapy. Metabolites were determined in 24-hour urine samples collected on treatment day 8, and the contributions of individual compounds, including the four isomers of 10-hydroxyamitriptyline and 10-hydroxynortriptyline to total excretion were calculated. Formation of (-)-E-10-hydroxyamitriptyline and (-)-E-10-hydroxynortriptyline apparently depends on the activity of cytochrome P450IID6 because negative correlations existed between the log metabolic ratio of dextromethorphan and the relative quantities of these enantiomers. In contrast, correlations were positive for nortriptyline, (+)-E-10 hydroxynortriptyline, (-)-Z-10-hydroxynortriptyline, and (+)-Z-10 hydroxynortriptyline. The mephenytoin hydroxylase seems to participate in side chain demethylation to the secondary and primary amines, because the log metabolic ratio of mephenytoin correlated negatively with the relative quantity of E-10-hydroxydidesmethylamitriptyline and positively with that of amitriptyline and its N-glucuronide. PMID- 1424410 TI - Pharmacokinetic and pharmacodynamic interaction between toloxatone, a new reversible monoamine oxidase-A inhibitor, and oral tyramine in healthy subjects. AB - We examined the influence of toloxatone, a new reversible monoamine oxidase-A inhibitor used in the treatment of depression, on tyramine-induced pressor effect in healthy volunteers. The maximum increase in systolic blood pressure produced by four single oral doses of tyramine administered during a meal and ranging from 100 mg to 800 mg was compared during repeated (3 to 5 days) administration of placebo, 200 mg toloxatone three times a day and 400 mg toloxatone three times a day in a single-blind, three-period crossover study. Toloxatone by itself had no significant influence on blood pressure. During administration of toloxatone, no significant increase in tyramine-induced increase in systolic blood pressure was observed for tyramine doses of 200 mg or less that are consistently higher than those associated with normal food intake. However, toloxatone increased the tyramine-induced increase in blood pressure after 400 mg tyramine (400 mg toloxatone three times a day) and 800 mg tyramine (200 mg toloxatone three times a day and 400 mg toloxatone three times a day). This pharmacodynamic interaction could be explained by an increase in tyramine systemic bioavailability in the presence of toloxatone. It is concluded that interaction between tyramine in meals and toloxatone is unlikely to occur in patients after long-term administration of the drug at therapeutic dosages. PMID- 1424411 TI - Hemodynamic effects of the use of oral snuff. AB - The hemodynamic effects during rest and exercise of oral snuff were investigated in an open, placebo-controlled study of nine habitual users of oral snuff. Blood pressure, heart rate, and central hemodynamics were measured noninvasively. Plasma concentrations of nicotine, cotinine, norepinephrine, and epinephrine, as well as neuropeptide Y-like immunoreactivity were measured before and after snuff intake during rest and exercise. Snuff intake induced a significant increase in heart rate and blood pressure and a decrease in stroke volume during rest. Hemodynamic changes were unrelated to nicotine or cotinine concentrations. Resting levels of norepinephrine and neuropeptide Y-like immunoreactivity were similar with or without snuff, whereas epinephrine was slightly increased 30 minutes after snuff intake. The exercise-induced increase in norepinephrine and neuropeptide Y-like immunoreactivity did not differ between the days subjects received snuff and the days they received placebo. In contrast, maximum work load was associated with a slight increase in circulating epinephrine after snuff intake. The findings suggest that snuff intake is associated with significant hemodynamic effects during rest but not during exercise. These effects could not be readily explained by activation of the sympathetic nervous system. PMID- 1424412 TI - Effects of temazepam on saccadic eye movements: concentration-effect relationships in individual volunteers. AB - Saccadic eye movements were analyzed after single oral doses of 20 mg temazepam and placebo in a randomized, double-blind crossover study in eight healthy volunteers. For an optimal evaluation of concentration-effect relationships, 18 blood samples and 43 effect measures were obtained over 33 1/2 hours. After placebo, saccadic peak velocity decreased within the first hour, with average values remaining 6.2% to 12.1% below baseline up to 15 hours after intake. After temazepam, significant changes in peak velocity occurred for 5 hours, with maximum decreases averaging 29.2% (95% confidence interval, 10.0 to 37.2). The apparent duration of effects ranged from 3 to 9 hours in individual subjects. Linear concentration-effect relationships were demonstrated for peak velocity, with individual slopes ranging from -0.11 to -0.46 deg/sec.(ng/ml)-1 (average r = -0.82, all p < 0.01). Differences in protein binding of temazepam did not account for the approximate fourfold variability in individual sensitivities to temazepam. By increasing the frequency of measurements, the accuracy of pharmacodynamic evaluations was clearly enhanced in this study. PMID- 1424413 TI - Pharmacodynamics and tolerability of L-654,066, a steroid 5 alpha-reductase inhibitor, in men. AB - A four-period, two-panel single rising-dose study (0.1 to 100 mg) was conducted in healthy men to investigate the pharmacodynamics and tolerability of L-654,066, a steroid 5 alpha-reductase inhibitor. Within each panel, six subjects received L 654,066 and two subjects received placebo at each dose level; the placebo subjects changed between periods so that each subject received placebo once. Testosterone and dihydrotestosterone were measured in serum at 0, 4, 24, and 48 hours after each treatment. L-654,066 was associated with a significant reduction in serum dihydrotestosterone concentrations, which was maximal at 48 hours after dose. Forty-eight hours after treatment, mean percentage of inhibition was 24% and 39% for the 0.1 and 0.5 mg doses, respectively, and ranged from 50% to 65% at doses from 1 to 25 mg and from 70% to 75% at doses from 50 to 100 mg. Testosterone serum levels did not show any significant difference between the various treatments, including placebo. PMID- 1424415 TI - Prediction of sotalol-induced maximum steady-state QTc prolongation from single dose administration in healthy volunteers. AB - The relationship between racemic sotalol plasma concentrations and QTc interval prolongation after both single-dose and repeated administration of three sotalol oral doses was studied in a randomized crossover protocol performed in 10 healthy volunteers. QTc interval increase was significant after the three single-dose sotalol administrations and was significantly related to the administered dose (p < 0.0001). In 21 of 30 analyses, QTc interval was linearly correlated with sotalol plasma concentrations. After the 320 mg dose, the linear model was a best fit for 90% of the cases, and no hysteresis was observed. After repeated sotalol administration, 69 of 87 QTc interval measurements at steady state could be predicted from the plasma concentration versus effect relationship established after single-dose 320 mg administration. Seventeen of 18 errors (94%) corresponded to QTc intervals that were significantly lower than predicted. These findings suggest that a short-term individual linear model determined after a 320 mg test dose of sotalol allows a good prediction of expected maximal increase in QTc duration in healthy subjects. PMID- 1424414 TI - Protection against aspirin-induced gastric lesions by lansoprazole: simultaneous evaluation of functional and morphologic responses. AB - The protective effect of lansoprazole, a new proton pump inhibitor, against aspirin-induced gastric lesions was studied in a double-blind crossover trial with a simultaneous measure of the functional capacities of the mucosal barrier (by a recording of the gastric potential difference) and of the morphologic changes in the mucosa (by gastric endoscopy). After 1 week of treatment with lansoprazole (30 mg per day) or placebo, each healthy volunteer received 1 gm aspirin by mouth. Recording of the gastric potential difference lasted for 3 hours and was followed by gastric endoscopy. Morphologic lesions induced by aspirin were effectively prevented by lansoprazole: Lanza score was 0.67 +/- 0.98 (mean +/- SD) versus 2.25 +/- 1.1 with placebo (p < 0.005, ANOVA). Conversely, the decrease in the gastric potential difference was similar. The inhibition of acid secretion induced by lansoprazole was therefore sufficient to prevent aspirin-induced mucosal lesions without reinforcing the defense capacities of the mucosa. This simple pharmacologic model makes it possible to simultaneously evaluate the functional and morphologic effects of aspirin intake on the gastric mucosa. PMID- 1424416 TI - Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function. AB - OBJECTIVE: To assess whether fluvoxamine alters the pharmacokinetics of alcohol or potentiates alcohol-related impairment of cognitive function. METHODS: The study design required partially "blinded" balanced crossover studies, each involving 12 healthy male volunteers who each received a 40 gm dose of intravenous or oral alcohol after single and multiple doses of 50 mg fluvoxamine. Main outcome measures for pharmacokinetics were venous blood alcohol and plasma fluvoxamine. Main outcome measures for pharmacodynamics were word recall, simple and choice reaction time, number vigilance, memory scanning, and word recognition. RESULTS: The pharmacokinetics of intravenous alcohol were not affected by concomitant administration of fluvoxamine. Compared with placebo alcohol, alcohol slightly increased the rate of fluvoxamine absorption, but the area under the plasma concentration-time curve from 0 to 12 hours at steady state was unchanged. As expected, alcohol significantly impaired cognitive function in volunteers. However, fluvoxamine did not potentiate the effects of alcohol and in some instances appeared to reverse the effects or reduce their duration. Fluvoxamine was well tolerated: only mild adverse effects were reported, and none of those required intervention. CONCLUSION: Fluvoxamine does not interact significantly with alcohol or potentiate alcohol-related impairment of cognitive function. PMID- 1424417 TI - Comparison of intravenous ketorolac with morphine for postoperative pain in children. AB - Ninety-two children from 3 to 12 years of age were given intravenous morphine or ketorolac by titration, or ketorolac by bolus injection for moderate or severe postsurgical pain in a double-blind randomized parallel-group study. Pain scores were assessed every 5 minutes until pain relief was complete, and then every 15 minutes for 8 hours or until pain returned. Twenty-nine of 30 patients receiving morphine and 25 of 30 patients in each group receiving ketorolac achieved pain relief. The subjects in the morphine group required statistically fewer doses for analgesia than the subjects in the ketorolac groups. The sums of pain intensity differences calculated from the start of the study numerically favored morphine, but the sum of pain intensity differences from pain relief until 50% withdrew were significantly better in the ketorolac groups. Median durations of analgesia from initial drug administration were 170, 190, and 225 minutes in the morphine, ketorolac titration, and ketorolac bolus groups, respectively. The most common side effect was injection site pain. Analgesia after intravenous ketorolac developed more slowly but was sustained better than morphine. PMID- 1424418 TI - Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. AB - The pharmacokinetics of cyclosporine was studied in six healthy volunteers after administration of the drug orally (10 mg/kg) and intravenously (3 mg/kg) with and without concomitant rifampin administration. Both blood and plasma (separated at 37 degrees C) samples were analyzed for cyclosporine concentration. For blood and plasma, respectively, clearances of cyclosporine were calculated to be 0.30 and 0.55 L/hr/kg, values for volume of distribution at steady state were 1.31 and 1.68 L/kg, and bioavailabilities were 27% and 33% during the pre-rifampin phase. Post-rifampin phase clearances of cyclosporine were 0.42 and 0.79 L/hr/kg, values for volume of distribution at steady state were 1.36 and 1.35 L/kg, and bioavailabilities were 10% and 9% for blood and plasma, respectively. Rifampin not only induces the hepatic metabolism of cyclosporine but also decreases its bioavailability to a greater extent than would be predicted by the increased metabolism. The decreased bioavailability most probably can be explained by an induction of intestinal cytochrome P450 enzymes, which appears to be markedly greater than the induction of hepatic metabolism. PMID- 1424419 TI - Influence of lansoprazole treatment on diazepam plasma concentrations. AB - The possible influence of long-term treatment with lansoprazole on the single dose pharmacokinetics of diazepam was investigated in 12 healthy male volunteers. In this double-blind randomized crossover study, 60 mg lansoprazole or placebo was administered once daily for 10 days. One hour after administration on day 7, 0.1 mg/kg diazepam was administered intravenously, and blood was collected up to 96 hours after the injection for plasma diazepam and desmethyldiazepam measurement. During the placebo session, the plasma elimination half-life, clearance, and volume of distribution of diazepam were 26.0 +/- 1.6 hours, 22.5 +/- 1.1 ml/hr/kg, and 0.82 +/- 0.04 L/kg, respectively. These parameters were not significantly different during the lansoprazole session. The mean plasma concentrations of desmethyldiazepam were similar in both sessions. These findings illustrate that long-term treatment with a therapeutic dose of lansoprazole does not interfere with the metabolism of diazepam. PMID- 1424420 TI - Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus. AB - OBJECTIVE: To determine if therapeutic doses of naproxen affect the in vivo disposition of zidovudine. METHODS: This was designed as a randomized, two period, two-treatment, crossover study. The patients were 12 men infected with human immunodeficiency virus who had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. On two separate occasions 14 days apart, patients received either zidovudine alone (200 mg every 4 hours while awake) or zidovudine (200 mg every 4 hours while awake) and naproxen (500 mg every 12 hours for 4 days). On the morning of the fifth day, each patient received the final dose of each regimen and blood and urine were serially collected for 8 hours. Pharmacokinetic parameters (area under the serum concentration-time curve [AUC], maximum plasma concentration, terminal half-life, renal clearance, and urinary recovery) were assessed for zidovudine and its glucuronide metabolite. MAIN RESULTS: Naproxen had no significant effect (< 10% difference between treatment means, p > 0.15, ANOVA) on the above pharmacokinetic parameters for both zidovudine and its metabolite. Although the power of the study to detect these small differences was < 80% at the 5% significance level, differences ranging from 12.6% for AUC to 38.8% for urinary recovery could be detected with 80% power. CONCLUSION: Therapeutic doses of naproxen do not significantly affect the pharmacokinetic disposition of zidovudine. PMID- 1424421 TI - Erythromycin breath test predicts oral clearance of cyclosporine in kidney transplant recipients. AB - It has been shown recently that cyclosporine is largely metabolized by P450IIIA (CYP3A), an enzyme whose catalytic activity varies significantly among patients. To determine whether heterogeneity in P450IIIA activity contributes to interpatient differences in cyclosporine dosing requirements, the oral pharmacokinetics of the drug were determined in 20 stable kidney transplant recipients. P450IIIA activity was then measured in each patient by use of the erythromycin breath test. In the 16 patients who were at steady state, the logarithm of the apparent oral clearance of cyclosporine correlated significantly with the rate of 14CO2 exhaled in breath after intravenous administration of [14C N-methyl]erythromycin (r = 0.55, p = 0.03). No significant correlations existed between apparent oral clearance and age, high-density lipoprotein cholesterol or low-density lipoprotein cholesterol, or hematocrit in these patients. We conclude that heterogeneity in P450IIIA activity significantly contributes to interpatient differences in dosing requirements of cyclosporine in kidney transplant patients. PMID- 1424422 TI - Fluoxetine impairs clearance of alprazolam but not of clonazepam. AB - Volunteer male subjects received single 1.0 mg oral doses of alprazolam and of clonazepam on two occasions, during coadministration of 40 mg/day fluoxetine or of placebo. When the sequence of trials was placebo first and fluoxetine second, fluoxetine coadministration significantly prolonged alprazolam half-life (20 versus 17 hours) and reduced clearance (48 versus 61 ml/min). No effect of fluoxetine was seen when fluoxetine was given first and placebo second, because norfluoxetine persisted into the placebo phase even though fluoxetine had been discontinued 2 weeks earlier. Fluoxetine had no significant effects on clonazepam elimination half-life or clearance regardless of the sequence of fluoxetine and placebo administration. In the fluoxetine-placebo sequence, fluoxetine significantly increased the rate of clonazepam absorption. Thus fluoxetine appears to impair clearance of alprazolam by way of microsomal oxidation but does not alter clearance of clonazepam by way of nitroreduction. The very slow elimination of norfluoxetine should be considered in the design of clinical or pharmacokinetic studies that involve fluoxetine. PMID- 1424423 TI - Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer. AB - The single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone have been determined in patients with moderate to severe cancer pain. The mean +/- SD elimination half-life after single-dose administration of intravenous (4.6 mg to 9.1 mg) and oral (9.1 mg) oxycodone was 3.01 +/- 1.37 hours and 3.51 +/- 1.43 hours, respectively. After intravenous administration, the mean +/- SD volume of distribution was 211.9 +/- 186.6 L, and the mean +/- SD total plasma clearance was 48.6 +/- 26.5 L/hr. The mean absolute oral bioavailability of oxycodone was 87%, and the mean +/- SD volume of distribution after oral administration was 249.1 +/- 204.3 L. When administered orally as 10 mg oxycodone hydrochloride every 4 hours, there was no accumulation of oxycodone at steady state and the mean +/- SD steady-state concentration was 34.6 +/- 10.3 micrograms/L. Intravenous oxycodone produced a faster onset of pain relief than oxycodone tablets, but the duration of analgesia was approximately the same (4 hours). However, the incidence of side effects and their severity were significantly higher (p < 0.05) for intravenous oxycodone than for oxycodone tablets. The marked interindividual variation observed in the pharmacokinetics and pharmacodynamics of oxycodone in this study supports the need for individualized dosing regimens. PMID- 1424425 TI - Time course of tolerance to apomorphine in parkinsonism. AB - We sought to determine if tolerance developed to the antiparkinsonian effects of apomorphine and, if so, what temporal factors influenced its development. Seven patients with parkinsonism and motor fluctuations received short (6-hour) and long (22- to 31-hour) apomorphine infusions. Tolerance was evaluated by comparison of the responses to test doses of apomorphine that were administered before and after each infusion. The responses to the test doses that followed either infusion were reduced by 35% after the short infusion and by 68% after the long infusion, although plasma apomorphine levels were similar to or higher than levels achieved with preinfusion test doses. The duration of improvement in parkinsonism after discontinuation of the long infusion was briefer than that after the short infusion. We conclude that tolerance to apomorphine occurs in parkinsonism, and the loss of response is greater after longer periods of drug administration. PMID- 1424424 TI - Clinical pharmacology of nicorandil in patients with congestive heart failure. AB - Nicorandil is a nicotinamide derivative with a potential role in human therapeutics because of its potent vasodilating properties. The pharmacokinetics of oral nicorandil administration and the relationships between plasma nicorandil concentration and hemodynamic responses were examined in 25 patients with moderate to severe congestive heart failure. The dose range from 10 to 60 mg was studied. Elimination half-life for this dose range was substantially longer than that previously reported in normal volunteers. Total area under the curve increased in a curvilinear fashion with progressive dose increments, indicating a disproportionate increase in systemically available drug at higher doses. Hemodynamic responses generally correlated well with plasma nicorandil concentration, with rapid loss of cardiovascular activity corresponding to the efficient clearance of nicorandil. PMID- 1424426 TI - Paradoxical pharmacodynamic effect of atropine on parasympathetic control: a study by spectral analysis of heart rate fluctuations. AB - The power spectrum of instantaneous heart rate fluctuations was used to determine the optimal doses of atropine that induce a maximal vagolytic or vagomimetic effect. In a crossover placebo controlled study, eight volunteers received increasing bolus doses of intravenous atropine (0.1 to 2.3 mg per subject) or placebo, and frequency bands of the power spectrum were integrated. During atropine administration a significant bimodal dose dependence was observed for the respiratory peak (0.2 to 0.4 Hz, p = 0.0006), the midfrequency band (0.09 to 0.15 Hz, p = 0.0035), and mean heart rate (p < 0.0001). Low doses (< 0.4 mg per subject) increased the respiratory and midfrequency band power, with maximal response at 0.2 mg per subject. Larger doses of atropine, 0.5 to 2.3 mg per subject, markedly reduced the power in all frequency bands in a dose-dependent way. The corresponding changes in mean heart rate were simultaneous, but in the opposite direction. We suggest that the respiratory peak of the power spectrum can be used to optimize drug effects on cardiac parasympathetic control. PMID- 1424427 TI - Population pharmacodynamics of doxacurium. AB - The nonlinear mixed-effects modeling (NONMEM) computer program was used to investigate the variability in the duration of doxacurium-induced neuromuscular block in 408 patients enrolled in phase II and phase III clinical trials of doxacurium. Spontaneous recovery data in the 10% to 90% block range from all patients were pooled and fitted to a linear model. Two parameters were estimated: (1) the slope, which is related to the pharmacokinetics and to the steepness of the dose-response curve, and (2) the intercept, which is linearly related to dose but has no physiologic meaning. The primary goal was to determine the factors affecting the slope by use of univariate and multivariate analyses techniques. Estimates of the slope ranged from 0.67% to 1.1% block/min (interindividual variability, 39%). Factors with clinically significant effects on the slope included the following: age, obesity, and anesthesia type. Thus these factors influence the time course of doxacurium-induced block and may require individualization of dose. PMID- 1424428 TI - The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy. AB - The effect of the selective serotonin reuptake inhibitor citalopram on diabetic neuropathy symptoms was examined in a double-blind, placebo-controlled, crossover study for two 3-week periods. Citalopram was given as a fixed dose of 40 mg/day. Data from 15 patients could be included in the statistical analysis. Citalopram significantly relieved the symptoms of neuropathy as measured by both observer- and self-rating in comparison with placebo. The steady-state plasma concentration of citalopram was 10 to 890 nmol/L. There was no significant relationship between the plasma concentration of citalopram and the effect of treatment as measured by observer- or self-rating. Two of 17 patients, both receiving citalopram, left the study because of side effects (nausea and vomiting or gastric upset and diarrhea). Side-effect ratings were significantly higher during administration of citalopram than during administration of placebo, but citalopram was generally well tolerated. Compared with earlier results obtained with imipramine administered on the basis of plasma level monitoring, citalopram appeared to be less effective, but seemed to be better tolerated. PMID- 1424429 TI - Pharmacologic maintenance of abstinence in patients with alcoholism: no efficacy of 5-hydroxytryptophan or levodopa. AB - Pharmacologic enhancement of central nervous system serotonin and dopamine functions has been postulated to improve maintenance of abstinence in patients with alcoholism. To test this hypothesis, patients with alcoholism who completed a 42-day inpatient treatment program were randomized to be administered, in a double-blind fashion, either 5-hydroxytryptophan and carbidopa, levodopa and carbidopa, or placebo for 1 year. Eight of 31 patients who entered the analysis remained abstinent from alcohol for 1 year; however, there was no significant effect of the treatment condition on maintenance of abstinence. Baseline psychologic measures showed that patients who abstained from alcohol had more education and higher scores on memory function tests. Measures of cerebrospinal fluid obtained before the start of the study indicated that all patients who had higher concentrations of the dopamine metabolite homovanillic acid relapsed, suggesting that further research is needed to elucidate the role of dopamine in alcoholism. PMID- 1424430 TI - Enantioselective pharmacokinetics and pharmacodynamics of dl-threo methylphenidate in children with attention deficit hyperactivity disorder. AB - Nine boys with attention-deficit hyperactivity disorder took part in a study in which d-methylphenidate, l-methylphenidate, dl-methylphenidate, or placebo were administered in a double-blind, four-way, randomized, crossover design. Plasma levels of the isomers of methylphenidate were monitored by means of an enantioselective assay method. The ability of the children to perform tasks that required sustained attention was monitored by a battery of computer tests. There was no evidence of interconversion between the enantiomers in vivo, although the presence of the d-isomer significantly altered the pharmacokinetics of the l antipode. The presence of the l-isomer did not affect the pharmacokinetics of d methylphenidate. The computer tests revealed a drug-induced improvement in sustained attention that was entirely attributable to the d-enantiomer. There was no evidence to suggest that the effectiveness of d-methylphenidate was in any way compromised by the presence of its antipode. PMID- 1424431 TI - Pharmacokinetics of fosinopril. PMID- 1424432 TI - Vancomycin levels and acute renal failure. PMID- 1424433 TI - Biosynthesis and distribution of fibronectin in normal and osteoarthritic human cartilage. AB - The biosynthesis of fibronectin was determined in explants from normal and osteoarthritic human cartilage after metabolic labeling and immunoprecipitation. Each sample of osteoarthritic cartilage was divided into three regions taken at different distances from the eburnated bone area. Only full depth cartilage samples were taken into consideration. We could detect a low level of fibronectin biosynthesis in normal cartilage. In osteoarthritic cartilage increased synthesis of fibronectin was demonstrated, the most important in the region close to the eburnated area. Increased synthesis, although to a lower extent, was also demonstrated in the two other regions at increasing distances from the eburnated areas. Immuno-histological examinations performed on tissue samples and similar studies on articular chondrocyte cell cultures confirmed the accumulation of newly synthesized fibronectin in pathological conditions. PMID- 1424435 TI - Non-invasive assessments of compliance of the aortic wind-kessel in man derived from pulse pressure/storage volume ratio and from pulse wave velocity. AB - Two noninvasive methods for assessment of the compliance (1/E') of the aortic windkessel in man are presented and were tested for their ability to detect increases in stiffness of the aorta induced by atropine (0.012 and 0.024 mg/kg sequentially) in the presence and absence of a beta-blockade with propranolol 240 mg (n = 9). Method A, based on the calculation of the relation between pulse pressure and systolic storage volume of the aorta, requires measurement of blood pressure, systolic and diastolic time intervals and stroke volume. Method B, based on measurement of pulse wave velocity along the aorta also requires several anthropometric data (body surface area, age). Both methods were able to detect a dose-dependent increase in E' following atropine injections; method A has greater relative changes than method B. The average maximal increases were 90 and 40 percent of the baseline before atropine. The daily baselines of E' averaged 0.6 Torr x cm-3 for method A and 0.9 Torr x cm-3 for method B. Propranolol itself did not influence E' but dampened the atropine effects. The results from method A and B were correlated with r = 0.70 and 0.60 resp. (p < 0.01). The results suggest the use of these relatively simple techniques for evaluation of aortic compliance under influence of varying pathophysiological conditions or/and pharmacological interventions. PMID- 1424434 TI - Myocardial creatine kinase-MB concentration in normal and explanted human hearts and released from hearts of patients with acute myocardial infarction. AB - Using an enzyme immunoassay of creatine kinase (CK)-MB concentration commercially available for diagnosis of acute myocardial infarction (AMI), we studied CK-MB concentrations in myocardium of subjects who died from noncardiac causes and in cardiac explants of patients with either coronary heart disease or cardiomyopathy who underwent cardiac transplantation. Secondly, CK-MB concentrations were measured in serial plasma samples of 93 patients with AMI. By calculation of cumulatively released amounts of CK-MB and cumulatively released activities of CK, aspartate aminotransferase (AST) and alpha-hydroxybutyrate dehydrogenase (HBDH), we obtained values of the proportions in which these quantities were released from the myocardium. Taking a myocardial HBDH activity of 152 U/g as a reference value, the released activities of CK and AST, and the released mass of CK-MB per gram of myocardium were calculated. These values were compared to the corresponding quantities in myocardium of normal hearts and in explanted myocardium. Normal hearts differ from explanted myocardium and from "infarcted" hearts with respect to CK-MB concentration, but not with respect to CK, AST and HBDH activities. The wide range of CK-MB concentrations in normal hearts (1-515 micrograms/g) suggests variable expression of the CK-MB gene. The presence of CK MB is not confined to cardiac tissue. CK-MB concentration in 12 samples of human skeletal muscle equalled 27 +/- 1 micrograms/g (2.1 +/- 0.5% of total CK activity). In conclusion, the mean concentration of CK-MB in normal hearts is low (139 micrograms/g) with a high variation coefficient (127%), but is high (369 micrograms/g) with a small variation coefficient (31%) in explanted hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424436 TI - Anticholinergic influences of biperidene on the EEG effects of haloperidol. AB - 15 normal volunteers demonstrated after 14 days of haloperidol (HA) medication (3 mg/day) a higher mean power density (mpd) in all frequency bands of the EEG power spectra combined with a higher theta and a lower alpha center frequency (cf). After further 7 days of HA medication together with the additionally applied anticholinergic biperidene (BI) (6 mg/day) the HA effects were antagonized especially in the theta cf and the alpha mpd. The higher delta and theta mpd were not antagonized. The EEG spectra of the pre- and posttreatment condition did not differ. There was a significant effect of HA on the "Adjective Mood Scale" and on the "Complaint List", which disappeared during the additional BI medication. The reaction times were prolonged with HA and decreased with BI. Blocked dopaminergic impulses on the cholinergic EEG mechanisms possibly produce higher amplitudes during HA medication. Schizophrenic patients treated with neuroleptic drugs showed similar EEG spectra in previous studies during rest but not during motor activation. PMID- 1424437 TI - Differential effects of transition metal ions on in vitro lipid peroxidation of human serum and protein precipitated from serum. AB - Elevated concentrations of lipid peroxidation products in serum have been documented in some common human diseases. In addition, several reports indicate that peroxidative damage of tissues in laboratory animals are enhanced in acute toxicity from transition metal ions. We studied the effects of four commonly encountered transition metal ions in human acute toxicity: copper, iron, mercury and lead on in vitro lipid peroxidation of human sera. Cupric and ferric ions caused a significant increase in lipid peroxidation products while mercuric and lead ions had no effects. Lipid peroxidation products in sera incubated with 1 mM cupric ion were increased by 210-248% following 24 h of incubation and 340-480% after 48 h of incubation, while the increases were significantly lower in the aliquots of same serum pools supplemented with same molar concentration of ferric ions (110-115% after 24 h and 137-141% following 48 h). On the other hand the effects were reversed when lipoproteins coprecipitated with other serum proteins were incubated with cupric and ferric ions. Under such conditions increases of lipid peroxidation products were significantly higher with ferric ions (240% after 24 h and 600% after 48 h) compared to cupric ions (20% following 24 h and 25% following 48 h). Such differential behavior of cupric and ferric ions in promoting lipid peroxidation can be explained with a different degree of binding of such ions with serum proteins. PMID- 1424438 TI - Molecular analysis of the fragile X syndrome. AB - Carriers of the fragile X mutation possess more than the normal number of copies of a trinucleotide repeat (CGG) within the coding region of a gene designated as FMR-1 in Xq27. The clinical phenotype is determined by the number of copies of the CGG repeat. DNA-based methods for the detection of the fragile X mutation are now available which greatly assist in the genetic diagnosis of this disorder. Direct detection of the mutation enables the identification of fragile X negative normal transmitting males and fragile X negative carrier females. PMID- 1424439 TI - Primary immunodeficiencies in the USSR: update of a nine-year study. AB - During the period January 1982-January 1991, 372 patients with primary immunodeficiencies from all the regions of the USSR were detected in a specialized unit. Incidence of main clinical manifestations and death rates are reported. Differences with other national registries are discussed. PMID- 1424440 TI - Quality improvement in the modern clinical laboratory: the regulatory and accreditation perspective. PMID- 1424441 TI - Allele-specific methylation in the 5'-regulatory region of class II DQ beta genes in the human major histocompatibility complex (MHC): relationship to autoimmune disease susceptibility. AB - The DNA methylation state of the 5'-regulatory region of human HLA-DQ beta genes was examined. Two restriction enzymes were utilized to detect methylated (meCG) dinucleotides in the 5'-regulatory region of the DQ-beta genes: the restriction enzyme Msp I, which recognizes CCGG and CmeCGG, and Hpa II recognizes only the unmethylated CG sequence. DNA samples were prepared from 95 HLA-typed individuals including 40 B-lymphoblastoid cell lines and peripheral blood leukocytes of 55 individuals. Of these samples, 20 were from parents of individuals with insulin dependent diabetes. Allele specific methylation was observed in particular DR associated DQ-beta gene alleles. The DQw8 (DQw3.2) allele, most DQw7 (DQw3.1) alleles, and the DR3-associated DQw2 allele were all unmethylated. The parental methylation state was stably transmitted to offspring. Because these DQ alleles are highly associated with several autoimmune diseases, our results raise the possibility that the regulation of expression of these particular DQ-beta alleles might be different from that of other alleles, and that the 5'-regulatory DNA sequences of these particular DQ beta alleles may be responsible for, or contribute to, susceptibility to autoimmune diseases. PMID- 1424442 TI - Staging prostatic cancer. PMID- 1424443 TI - High-resolution computed tomography of drug-induced lung disease. AB - In order to determine the potential clinical utility of high-resolution CT (HRCT) in the assessment of drug-induced lung disease, we reviewed the chest radiographs and HRCT scans of 23 patients and five normal controls. The radiographs and HRCT scans were reviewed separately in random order by two independent observers who were not aware of the relative numbers of patients and controls. Abnormal findings were detected in the affected patients in 17/23 radiographs compared to 23/23 HRCT scans. The patients included five cases of bleomycin toxicity, five cases of nitrofurantoin toxicity, two cases each of penicillamine, busulphan, BCNU and amiodarone toxicity, and one case each of cyclophosphamide, procainamide, mitomycin and methotrexate toxicity. The HRCT appearances could be grouped into four categories according to their dominant pattern and distribution of disease. These include fibrosis with or without consolidation (n = 12), ground glass opacities (n = 7), widespread bilateral consolidation (n = 2), and bronchial wall thickening with areas of decreased attenuation (n = 2). The results of this study indicate that HRCT is more sensitive than the radiograph in the detection of drug-induced lung disease. The appearances demonstrated by HRCT reflect the pathological mechanisms of drug-induced lung disease. PMID- 1424444 TI - Imaging of orbitofrontal cholesterol granuloma. AB - The radiological findings in 31 patients with a histologically proven orbitofrontal cholesterol granuloma are presented. Plain films and computed tomography (CT) both show a characteristic lytic lesion allowing a reasonably confident diagnosis to be made preoperatively, thus facilitating appropriate surgery. The most important differential diagnoses on clinico-radiological grounds are lacrimal gland carcinoma and dermoid cyst. On plain films cholesterol granulomas typically show constancy of site, lysis of the superior orbital margin, frequent extension into the frontozygomatic process and absent or minimal surrounding sclerosis. On CT ragged bone destruction with a soft tissue mass no denser than brain extending extraperiosteally into the orbit are the most typical features. MRI and other imaging modalities are discussed. PMID- 1424445 TI - Tongue cancer treated with irradiation: assessment with MR imaging. AB - We examined the usefulness of MRI in differentiating post-radiation scar tissue from the residual tumour. Ten consecutive patients who underwent MR imaging before and after radiation therapy were assessed prospectively. T1- and T2 weighted images using a 1.5 unit were obtained in 10 patients (3 T1, 6 T2, 1 T3) at 1 week before irradiation, and 2 weeks, 2 months, 4 months, 6 months and every 6 months thereafter following completion of radiation. Although all T2 and T3 tumours demonstrated high signal intensity compared to muscle on T2-weighted images, the T1 tumour could be demonstrated in only one of three patients. Six patients in whom the primary tumour clinically disappeared demonstrated low signal intensity on T2-weighted images until 4 months after completion of radiation therapy (range 1 week to 4 months). This study suggests that MRI can detect primary tumours larger than T2 (2 cm), and may be useful in assessing the effectiveness of therapy for tongue cancer. PMID- 1424446 TI - Benign mimics of soft tissue sarcomas. AB - We reviewed all new patients referred for treatment to the Sarcoma Unit at the Royal Marsden Hospital with a clinical diagnosis of soft tissue sarcoma (STS) during the course of 1 year (1989-1990). Of 118 patients, 65 (55.1%) had primary STS, 26 (22.0%) had recurrent STS, 19 (16.1%) had benign soft tissue tumours and eight (6.8%) had malignant tumours other than STS involving soft tissues and presenting clinically as soft tissue tumours. All patients underwent CT scanning which was used to assist diagnosis, assess operability or for radiotherapy planning. The CT findings of the benign lesions, all clinically suspicious of sarcoma, are discussed. The role of CT in the identification and management of these cases is emphasized. PMID- 1424447 TI - Imaging of alveolar soft part sarcoma. AB - The imaging investigations in six patients with alveolar soft part sarcoma (ASPS) are reviewed. Five patients presented with a pelvic or lower limb mass and one with haemoptysis from pulmonary metastases. Magnetic resonance imaging (MRI), CT, Doppler US and angiography studies demonstrated the highly vascular nature of this rare tumour and the frequent occurrence of pulmonary and intracranial metastases. Previously unreported Doppler US and MR evidence of multiple enlarged vessels and high blood flow within primary and secondary ASPS tumours is emphasized. Imaging is of considerable importance both for pre-operative localization and long term surveillance of this slow growing but invariably disseminating tumour. PMID- 1424448 TI - Gas-containing ganglia of the hip. AB - Three cases of ganglia related to the hip containing gas are presented. Gas may be shown by conventional radiography, linear tomography or computed tomography. All three cases had advanced degenerative disease of the joint. In degenerative disease, ganglia form through a pathway which allows the transfer of intra articular gas into the ganglion. It is important to differentiate this phenomenon from overlying bowel gas and other causes of gas within soft tissues. It is the most specific radiological feature of ganglia around the hip. PMID- 1424449 TI - The accessory navicular--an important cause of medial foot pain. AB - The accessory navicular is a commonly occurring accessory ossicle of the foot. In most instances this is an incidental finding. In some patients, the accessory navicular is the direct cause of foot pain. We present 10 such cases. The typical clinical picture is of a young female patient who presents with chronic or acute on chronic medial foot pain centered over the medial side of the navicular. The patient is usually physically active on her feet and localizes the pain accurately. Plain radiography reveals an accessory navicular united to the navicular by a synchondrosis (Type II). The diagnosis can be confirmed by showing increased localized uptake of isotope on a technetium 99m MDP bone scan. In some cases, the accessory navicular is mistaken for a fracture. Awareness of this accessory ossicle causing such symptoms should lead to the correct diagnosis. PMID- 1424450 TI - Renal transplant sonography: correlation of Doppler and biopsy results in cellular rejection. AB - Seventy-one patients with allograft dysfunction had concomitant Doppler sonography and percutaneous biopsy. Forty-one had biopsy proven acute cellular rejection and eight had acute cellular rejection in combination with acute tubular necrosis. Real time ultrasonic appearance and various parameters of Doppler waveform were studied and compared with 30 controls who had a long period of stable function with no previous episodes of rejection or acute tubular necrosis (ATN). Morphological appearances were unhelpful in diagnosing rejection. A resistive index greater than 0.8 in the study group was highly specific for dysfunction but could not differentiate between acute rejection and ATN. However, two patients in the control group of normal transplants had a resistive index of 0.83. An early to mid diastolic notch was highly specific for acute rejection but of low sensitivity. It may be the only Doppler indication of cellular rejection and may be present when the resistive index is in the normal range. PMID- 1424451 TI - Renal artery embolization with ethanol and gelfoam for the treatment of ureteric fistulae with one year follow-up. AB - Two patients with ureteric fistulae who were unfit for reconstructive surgery were treated by renal ablation using intra-arterial ethanol, gelfoam fragments and in one case coils. In both cases the fistulae dried-up on the same day and both patients are well and normotensive a year later. Our conclusion is that renal ablation by arterial embolization with ethanol can be a valuable alternative to surgery to treat ureteric fistulae in patients who are poor surgical risks. PMID- 1424452 TI - The acute contrast enema in suspected large bowel obstruction: value and technique. AB - In order to determine the value of the acute contrast enema (ACE) as compared to the plain abdominal film for the diagnosis of colonic obstruction and to determine the optimal technique for performing this examination, we reviewed 140 cases performed over a 4 year period. The study shows that when provided with the case history and the plain abdominal films of patients referred for an ACE the diagnosis of colonic obstruction can be made with a sensitivity of 84% and a specificity of 72%, whereas the ACE has a sensitivity of 96% and a specificity of 98%. The ACE resulted in two false negatives, one false positive and one technical failure, analysis of which has enabled an optimal technique for the performance of this examination to be recommended. PMID- 1424453 TI - Clinico-radiological meetings: are they worthwhile? AB - The proceedings of 22 clinico-radiological meetings were analysed in order to assess some aspects of their benefits and cost. The mean duration of each meeting was 30.4 min. On average, the clinical and radiological details of eight patients were discussed at each meeting. The mean number of changes in the leading diagnosis was 1.6 per meeting, and a mean of 1.9 management decisions were made. A mean of 1.6 further radiological tests were recommended, offset by a mean of 0.7 scheduled investigations which were deemed no longer necessary. The cost of the salaries of the staff attending each meeting amounted to 73.82 pounds. Thus the cost of a revised leading diagnosis was calculated at 46.14 pounds whilst that of a management decision came to 38.85 pounds. The assumed educational benefits of these meetings and inevitable lost opportunity costs were not analysed. PMID- 1424454 TI - Case report: chronic spinal cord compression from extramedullary haematopoiesis in thalassaemia--MRI findings. AB - A 27-year-old-man with beta-thalassaemia/HbE presented with signs and symptoms of spinal cord compression due to epidural extramedullary haematopoiesis. Magnetic resonance images demonstrated spinal cord constriction and atrophy suggesting that the disease process was long-standing. On transverse T2-weighted images, high signal intensity was observed within the spinal cord suggestive of post compressive spinal cord myelomalacia or gliosis. PMID- 1424455 TI - Case report: selective occipital lobe hydrocephalus and agenesis of the left lobe of the liver in congenital myotonic dystrophy. AB - Myotonic dystrophy (Steinert's disease) is an uncommon familial autosomal dominant disease, characterized by progressive muscular atrophy and myotonia. Mental retardation, frontal baldness, cortical lenticular opacities and testicular atrophy are other prominent features of a disease that involves predominantly striated muscle. There is little information regarding this disease in the radiological literature. The present report introduces two additional findings involving the skull and the liver. PMID- 1424456 TI - Case report: small bowel volvulus presenting during pregnancy. AB - The diagnostic use of ionizing radiation during pregnancy is to be avoided whenever possible due to the risk to the unborn child. However, vomiting presenting after the first trimester of pregnancy is unusual, and if severe or persistent, requires investigation. We present a case where reluctance to expose the fetus to radiation could have resulted in a potentially serious delay in the diagnosis of maternal small bowel volvulus. PMID- 1424457 TI - Case report: CT diagnosis of nonobstructive left paraduodenal hernia. AB - The preoperative diagnosis of paraduodenal hernias (PH) can only be made radiologically. PH are seldom diagnosed preoperatively unless they cause bowel obstruction. We report an unusual case of a nonobstructive left PH diagnosed preoperatively by computed tomography (CT). The CT findings of internal hernias are discussed. PMID- 1424458 TI - Case report: diagnosis of metastatic leptomeningeal melanoma by contrast enhanced MRI. AB - A case of leptomeningeal melanoma metastases with a confusing clinical picture is presented. Despite repeated cytological examinations of the cerebrospinal fluid proving negative, the diagnosis was eventually made by magnetic resonance imaging with gadolinium DTPA enhancement. PMID- 1424459 TI - Case report: complete lung collapse--an unusual presentation of cryptococcosis. AB - Cryptococcosis presenting as an intrabronchial mass is not a recognized cause of complete lung collapse. This case report illustrates this extremely rare manifestation of pulmonary cryptococcosis, which mimicked primary pulmonary carcinoma clinically, radiologically and bronchoscopically. PMID- 1424460 TI - Just how harmful are diagnostic X-rays? The College response. PMID- 1424461 TI - The radiological investigation of oropharyngeal dysphagia. PMID- 1424462 TI - Health care reform. Questions for patients, physicians and society. PMID- 1424463 TI - Colorado health care reform. Prepared by CMS Board of Directors, August 21, 1992, approved by the CMS House of Delegates, September 13, 1992. PMID- 1424464 TI - Parent-professional partnership in Fremont County. PMID- 1424465 TI - Better communication. PMID- 1424466 TI - Bloodborne pathogen regs, tips on compliance. PMID- 1424467 TI - Medical records figure prominently in malpractice cases. A closed liability claims analysis. PMID- 1424468 TI - Special AMA report: (NDBRA). National Data Bank Response Association. PMID- 1424469 TI - Pedioscopy: the time has come. PMID- 1424470 TI - Diagnosis and management of hearing loss. PMID- 1424471 TI - Magnetocardiography. PMID- 1424472 TI - A miniature silicon diode matrix detector for in vivo measurement of 133Xe disappearance following local tissue injection. AB - A variety of biological processes can be studied from the washout of compounds labelled with a gamma emitter. Conventional systems for measurement of gamma radiation can detect count rates at both the low and high energy range of the indicator in question, 133Xe. However, silicon (Si) photodiodes have the capability of measuring the lowest energies (25-40 keV) of gamma and x-ray emitters with sufficient efficiency when applied on the skin surface and close to the indicator depot. The purpose of the present study was firstly to evaluate a portable Si photodiode matrix detector system, composed of 16 photodiodes, for in vivo measurement of disappearance rate constants of 133Xe following injection into subcutaneous (SC) or skeletal muscle (SM) tissues as compared with a stationary sodium iodide single crystal detector. Secondly, from these results, to evaluate the contribution from intra-tissue indicator diffusion and indicate means of avoiding influence from local diffusion in the washout curve of 133Xe. From the recorded 133Xe distribution in the depot proper, Si photodiodes in the matrix were selected for calculation of the washout. The Si matrix detector was reliable with a constant linearity and sensitivity within the range 20-38 degrees C and calibrated to +/- 1% between diodes. The in vivo investigations comprised two SC injections on humans with four measuring periods for comparison, and four SC and five SM injections on dogs, resulting in eight and five measuring periods for comparison. Only when the results obtained from the Si photodiodes at the position just above the count rate maximum were selected, was the contribution from diffusion significant. The ability to detect geometry changes is advantageous in studies with potential motion artefacts, such as during exercise. PMID- 1424474 TI - Non-invasive determination of systolic blood pressure by heart sound pattern analysis. AB - A new concept of non-invasive blood pressure measurement by heart sound pattern analysis is described. The known diagnostic criterion of the 'accentuated' second heart sound of a hypertensive patient is here converted into a computer-aided pattern-recognition process for the second heart sound, applicable over the entire scale of blood pressure. After a 'learning phase', during which the second heart sound is recorded, analysed and correlated with a set of systolic blood pressure values of the individual patient, the computer is able to determine systolic blood pressure of the same patient from the acoustic spectrum of the second heart sound with sufficient precision. The method is in principle suited for automatically repeated blood pressure measurements, but further development is still needed for conversion into a widely practicable procedure. PMID- 1424473 TI - A miniaturised force-torque sensor with six degrees of freedom for dental measurements. AB - Force-torque sensor systems capable of simultaneously measuring all six spatial degrees of freedom on solid bodies are not very widespread in the medical field, particularly because of the hitherto unacceptably large external dimensions. A sensor based on the strain gauge technique has been developed with a diameter of only 32.5 mm and height of 29 mm. The miniaturised supporting framework for the strain gauges has been cast in a single piece from a wax-plastic model by the one way mould principle. A sensitivity of 10 mN with an upper limit of 50 N is attained. PMID- 1424475 TI - Conductance studies of rat renal medulla for rapid estimation of extracellular electrolyte concentration. AB - A method is described for estimation of tissue extracellular electrolytes in fresh excised rat renal medulla on the basis of its electrical conductance. The inner medulla was placed between two standard flat electrodes and the conductance was measured at a frequency of 3.5 kHz. The data were corrected for the surface area and thickness of the tissue fragment. The standard conductance so determined clearly correlated with total electrolyte concentration, and Na+ and 2(Na+ + K+) concentrations in the whole tissue (r = 0.84, 0.81 and 0.77, respectively; P < 0.001). The method enables a rapid and simple estimation of medullary extracellular electrolytes, a variable that is physiologically more meaningful than whole tissue electrolyte concentration. PMID- 1424476 TI - Use of an oxygen multiwire surface electrode for the direct measurement of the distribution of alveolar PO2 at different inspired oxygen concentrations. AB - Experiments were performed in six anaesthetised, mechanically ventilated rabbits. After thoracotomy, a multiwire surface PO2 electrode was placed at the pleural surface by means of a special holder. The local distribution of PO2 was investigated at different values of inspired oxygen concentration (FIO2). The data were analysed in order to establish (a) whether the PO2 values measured at the lung surface reflect intra-alveolar PO2 and (b) that the distribution of these values represent real physiological differences between alveoli. The mean PO2 values were related to the calculated mean alveolar PO2 (PAO2) values (r = 0.97) indicating that it is possible to study PAO2 by local measurements. It can therefore be concluded that the technique used allows the study of the influence of different FIO2 values on the distribution of PAO2. Each local PAO2 value is the result of the corresponding local ventilation/perfusion ratio (VA/Q) therefore the distribution of PAO2 values represents the distribution of VA/Q. An increasing FIO2 causes an increasing heterogeneity of PAO2 and thus VA/Q leading to a concomitant increase in the alveolo-arterial oxygen difference. At the moment it is not possible to decide if this heterogeneity is primarily caused by heterogeneities in perfusion or ventilation. The results could throw fresh light on the effect of different ventilation procedures. PMID- 1424477 TI - Validation of a method of treating menorrhagia by endometrial ablation. AB - Menstrual blood loss was measured by intravenous injection of radioactive iron (59Fe) and whole-body counting in 19 women complaining of menorrhagia due to dysfunctional bleeding. Fifteen patients were then treated by radiofrequency endometrial ablation, after which blood loss was re-measured. The majority of the patients were bleeding excessively before treatment (mean 281 (SD 156) ml per cycle averaged over two cycles, range 49-665 ml, n = 19). In the 15 treated patients, average blood loss was reduced to 52 (SD 39) ml per cycle and the mean reduction in blood loss was highly significant (P < 0.001). These quantitative data correlate well with the patients' subjective reports. PMID- 1424478 TI - Mechanical parameters of human hair: possible application in the diagnosis and follow-up of hair disorders. AB - Mechanical analysis of human hair may provide the dermatologists with several markers of considerable diagnostic importance. In the present paper, using a new computerised experimental system, attempts were made firstly to interpret the curves of the elastic and viscous components of the mechanical behavior of human hair and secondly to determine characteristic parameters which correlate well with its structural features. In order to overcome methodological problems due to the inhomogeneous structure of human hair, mechanical parameters were defined which either depend on the cortical microstructure or correlate well with the size of hair medulla. PMID- 1424479 TI - Early exercise thallium-201 single photon emission computed tomography in unstable angina: a prospective study. AB - To evaluate the safety and diagnostic value of early symptom-limited exercise electrocardiography (ECG) and exercise thallium-201 single photon emission computed tomography (SPECT) in unstable angina (UA), 39 patients were studied prospectively soon after stabilization on medical treatment. No patient had a history of myocardial infarction (MI) or revascularization and patients with left bundle branch block were excluded. Exercise ECG and exercise thallium-201 SPECT were performed 8 +/- 4 days and 11 +/- 6 days respectively after admission to hospital. Seventeen out of 39 patients (44%) had positive exercise ECGs and 22 (56%) negative or inconclusive ones. Exercise thallium-201 SPECT was positive in 26 patients (67%) and negative in 13 patients (33%). Thirty-one patients underwent coronary arteriography and 24 of them proved to have significant coronary artery disease (CAD). The sensitivity, specificity and positive predictive value of exercise ECG in detecting CAD are 62%, 86%, and 94% respectively while the corresponding results are 96%, 100%, and 100% for exercise thallium-201 SPECT. Therefore, it is concluded that the early symptom-limited exercise test is safe in medically stabilized patients with UA. Early exercise thallium-201 SPECT is highly sensitive and predictive of the presence of significant CAD among patients in the early recovery phase of UA and can be used in selecting this group of patients for coronary angiography and other therapeutic strategies. PMID- 1424480 TI - Use of non-invasive finger blood pressure monitoring in the estimation of aortic pressure at rest and during the Mueller manoeuvre. AB - The aim of this investigation was to evaluate whether reliable estimates of aortic pressure can be derived using non-invasive finger blood pressure monitoring. Finger blood pressure (Ohmeda 2300 Finapres device; Finapres, Englewood, CO) was compared with simultaneous ascending aortic pressure measured with a catheter-transducer system both at rest and during acute negative intrathoracic pressure (the Mueller manoeuvre). Thirty-eight patients aged 17-73 years were studied. All were undergoing routine diagnostic or therapeutic cardiac catheterization. Beat-to-beat values of systolic, diastolic and mean non-invasive finger and invasive aortic blood pressure were measured at rest and factors which might have an influence on the difference between methods were examined. The mean finger-aortic difference was +5 +/- 14 mmHg for systolic, -2 +/- 7 mmHg for diastolic, -5 +/- 8 mmHg for mean and +6 +/- 13 mmHg for pulse pressure. In multivariate linear regression analysis, the difference in systolic pressure was related to aortic systolic pressure (standardized coefficient beta = -0.33, P = 0.01), heart rate (beta = 0.49, P < 0.000), age (beta = -0.29, P < 0.025) and height (beta = 0.40, P < 0.005). The linear regression equations to derive resting aortic pressures from the non-invasive finger pressure readings had correlation coefficients between 0.83 and 0.87 and standard errors of estimate between 6 and 14 mmHg. During the Mueller manoeuvre, Finapres reproduced average pressure changes reliably compared with intra-aortic pressure. Due to moderate inter-individual variation in the finger-aortic differences the correlation coefficients ranged from 0.83 to 0.93 and the standard errors of estimate from 3 to 6 mmHg. Non-invasive finger blood pressure monitoring could be used to estimate central aortic mean and diastolic blood pressure fairly reliably at rest, but with respect to systolic pressure the variance in finger-aortic difference was marked. The average intra-aortic pressure changes caused by the Mueller manoeuvre were reliably reproduced by the Finapres device. PMID- 1424481 TI - Thigh composition in young and elderly men determined by computed tomography. AB - Computed tomography (CT) was used to quantify components of the thigh in young (n = 13) and elderly (n = 11) men. Cross-sectional areas (CSA) of the total limb, total muscle plus bone, quadriceps compartment, hamstring compartment and bone were measured at each of five scan sites along the length of the thigh. Non muscle tissue (NMT) areas within the muscle compartments were measured using changes in density based on Hounsfield units. Skin plus subcutaneous fat areas and quadriceps and hamstring lean muscle areas were calculated by subtraction. Geometric formulae were used to calculate related volumes for each thigh component. Volumes were also predicted from regression equations employing thigh length and component CSA from single mid-limb CT scans. The results showed that while total thigh CSA was not different in elderly men, they had significantly smaller total muscle plus bone (13.0%), and quadriceps (26.4%), and hamstring (17.9%) muscle areas. The elderly men also had significantly greater CSA for skin plus subcutaneous fat (37.6%), and for NMT in the quadriceps (59.4%) and hamstring (127.3%) muscle compartments. These results suggest that comparisons of relative leg muscle strength between young and elderly men may be misleading due to the decrease in actual muscle tissue associated with ageing. Appropriate quantification of muscle size and CSA must be carried out before such comparisons can be meaningful. PMID- 1424482 TI - Plasma endothelin-1 during central hypovolaemia in man. AB - Endothelin-1 (ET-1) is a potent vasoconstricting peptide with effect on resistance as well as capacitance vessels. We followed ET-1 in arterial plasma together with heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and thoracic electrical impedance (TI) in seven men during central hypovolaemia induced by 50 degrees head-up tilt. During tilting plasma ET 1 increased from 1.1 +/- 0.2 to 1.4 +/- 0.3 pmol l-1 (mean +/- SE) concomitant with an increase in total peripheral resistance (TPR) (from 15 +/- 2 to 25 +/- 3 mmHg min l-1) (P < 0.01), and HR (from 67 +/- 2 to 94 +/- 5 beats min-1) (P < 0.01) while MAP remained unchanged. CVP decreased (from 1.8 +/- 0.9 to -1.6 +/- 1.0 mmHg) (P < 0.01) during tilting and remained unchanged during sustained tilt despite further reduction of central blood volume as recorded by TI. Presyncopal symptoms occurred after 28 +/- 6 min associated with decreases in HR (to 70 +/- 6 beats min-1), MAP (from 90 +/- 3 to 52 +/- 4 mmHg) and TPR (to 11 +/- 2 mmHg min l-1) (P < 0.01). At this time plasma ET-1 reached its highest level of 1.6 +/- 0.3 pmol l-1 (P < 0.01). Data show that head-up tilt is associated with increased plasma concentrations of ET-1 which may play a role in maintaining vascular tone in situations with a reduced central blood volume. PMID- 1424483 TI - Heart rate during haemorrhagic shock. AB - In a prospective study, heart rate and mean arterial pressure were related to estimated blood loss in 34 consecutive patients aged 23-92 years during resuscitation from haemorrhagic shock. Eighteen patients with a blood loss of less than 31 (1.9 [0.9-3.0] l) (median and range), corresponding to 34 (16-46) % of estimated blood volume, had a heart rate of 83 (60-160) beats min-1 and a mean arterial pressure of 62 (35-73) mmHg. In 16 patients with a blood loss of more than 3 l (4.0 [3.3-5.0] l) corresponding to 89 (35-100) % of the estimated blood volume, heart rate was 120 (110-160) beats min-1 (P < 0.05) and mean arterial pressure 52 (0-70) mmHg (P < 0.05). Six patients died due to severe bleeding (3.1 [2.5-5.0] l) with a heart rate of 129 (110-160) beats min-1 and a mean arterial pressure of 40 (0-70) mmHg. It is concluded that reversible hypovolaemic shock is associated with a relatively low heart rate (approximately 80 beats min-1) and that tachycardia (approximately 120 beats min-1) is associated with profound bleeding. Hypovolaemic shock with tachycardia may represent a transition to an irreversible stage. PMID- 1424484 TI - Relationship between hyperglycaemia and aerobic power in men with newly diagnosed type 2 (non insulin-dependent) diabetes. AB - The aim of the study described here was to evaluate aerobic function during exercise and its determinants in middle-aged men with newly diagnosed Type 2 (non insulin-dependent) diabetes. Using breath-by-breath technique, we measured O2 uptake at anaerobic (ventilatory) threshold and at peak exercise in a group of diabetic men (n = 19; fasting blood glucose 8.6 +/- 0.7 mmol l-1, mean +/- SEM) without any disease or medication that could have had an influence on exercise performance, and compared the results to those observed in non-diabetic healthy control men (n = 18). There were no differences in physical activity or smoking habits between the groups. Oxygen uptake was lower in the diabetic men than in the control men both at anaerobic threshold (15.0 +/- 0.8 vs. 18.8 +/- 1.0 ml min 1 kg-1, P < 0.01) and at peak exercise (25.3 +/- 1.5 vs. 31.1 +/- 1.4 ml min-1 kg 1, P < 0.01). In the diabetic men peak O2 uptake showed an inverse linear correlation with age (r = -0.71, P < or = 0.001), fasting blood glucose (r = 0.49, P < 0.05) and glucose response in an oral glucose tolerance test (r = 0.43, P < 0.05). In addition, long-term smoking was associated with impaired peak O2 uptake. In a stepwise multiple regression procedure 75% of the total variance of peak O2 uptake in the diabetic men was explained by age, post-load blood glucose response and smoking history. Thus, in addition to ageing and smoking, hyperglycaemia is correlated with impaired aerobic power in men with newly diagnosed Type 2 diabetes. PMID- 1424485 TI - Myocardial reperfusion in thrombolysis A 99Tcm-Sestamibi SPECT study in patients with acute myocardial infarction. AB - This study presents the outcome of myocardial scintigraphy performed before and after thrombolytic treatment in 16 patients with acute myocardial infarction using 99Tcm-Sestamibi (Cardiolite, Du Pont Scandinavia AB, Kista, Sweden). The patients were given 99Tcm-Sestamibi intravenously as soon as possible after the decision to give thrombolytic treatment. When the patients were in a clinically stable state after the thrombolytic treatment, myocardial perfusion was analysed with the gamma camera using single photon emission computerized tomography (SPECT). A second 99Tcm-Sestamibi tomography was carried out on the second to fourth day after the myocardial infarction. Data reconstruction was done with the 'Bull's eye technique'. Nine patients received thrombolysis < 3 h from the onset of pain. In this group six patients (66%) improved their myocardial perfusion by > 10% after treatment, while all seven patients who received treatment > or = 3 h after the onset of pain improved their myocardial perfusion by < 10%. This study emphasises the importance of early diagnosis and treatment of patients with acute myocardial infarction in order to salvage myocardium. PMID- 1424486 TI - [Thrombolytic therapy in acute myocardial infarct]. AB - The benefits, main pharmacological characteristics, indications, side effects and time limits for use of thrombolytic agents in acute myocardial infarction are reviewed. The authors also point out the strategies to follow in patients after thrombolytic therapy. PMID- 1424487 TI - [Irritable colon. Physiopathologic and therapeutic aspects]. AB - The authors review the pathophysiologic mechanisms involved in bowel motility and in its alterations. Several symptoms are present in a form of bowel disease usually defined as "irritable bowel", in which a lot of polymorphic aspects appear to coincide. The first part of the paper is concerned with the symptoms and suggested pathophysiology and pathogenesis of the disorder while the latter part deals with the non-pharmacologic and pharmacologic treatment options. PMID- 1424488 TI - [Short-term perioperative antibacterial prophylaxis using imipenem-cilastatin versus acylureide penicillins in pacemaker implantation. A 30-month follow-up]. AB - The authors have evaluated the efficacy of short term treatment with an imipenem cilastatin combination in a selected group of 72 patients undergoing implant or substitution of a pacemaker and with associated pathology potentially increasing the risk of infection. After 30 months' follow-up, the authors underline the efficacy and advantages of this treatment. PMID- 1424489 TI - [Odontostomatological changes induced by drugs. I]. AB - The purpose of the present review is to describe the unwanted effects of drugs or chemicals in the orofacial region. The authors take into consideration the alterations of salivation such as xerostomia and ptyalism, disturbances of sense of taste, halitosis and pain and swelling of the salivary glands. The dental surgeon who suspects that an oral alteration might be a drug reaction can play an important role in preventing the development of more severe toxic effects. All this points to the importance of the knowledge of pharmacology for dental practitioners. PMID- 1424490 TI - [Proposals for ambulatory care of obesity]. PMID- 1424491 TI - [Pulmonary aging. Meeting at the Istituto Superiore di Sanita in Rome]. PMID- 1424493 TI - Categorical perception of facial expressions. AB - People universally recognize facial expressions of happiness, sadness, fear, anger, disgust, and perhaps, surprise, suggesting a perceptual mechanism tuned to the facial configuration displaying each emotion. Sets of drawings were generated by computer, each consisting of a series of faces differing by constant physical amounts, running from one emotional expression to another (or from one emotional expression to a neutral face). Subjects discriminated pairs of faces, then, in a separate task, categorized the emotion displayed by each. Faces within a category were discriminated more poorly than faces in different categories that differed by an equal physical amount. Thus emotional expressions, like colors and speech sounds, are perceived categorically, not as a direct reflection of their continuous physical properties. PMID- 1424492 TI - On the evolution of language and generativity. AB - One of the properties that most conspicuously distinguishes human language from any other form of animal communication is generativity. Language with this property therefore presumably evolved with the Homo line somewhere between H. habilis and H. sapiens sapiens. Some have suggested that it emerged relatively suddenly and completely with H. sapiens sapiens, and this view is consistent with (a) linguistic estimates as to when vocal language emerged, (b) the relatively late "explosion" of manufacture and cultural artifacts such as body ornamentation and cave drawings, and (c) evidence on changes in the vocal apparatus. However, evidence on brain size and developmental patterns of growth suggests an earlier origin and a more continuous evolution. I propose that these scenarios can be reconciled if it is supposed that generative language evolved, perhaps from H. habilis on, as a system of manual gestures, but switched to a predominantly vocal system with H. sapiens sapiens. The subsequent "cultural explosion" can then be attributed to the freeing of the hands from primary involvement in language, so that they could be exploited, along with generativity, for manufacture, art, and other activities. PMID- 1424494 TI - Probing the cognitive representation of musical time: structural constraints on the perception of timing perturbations. AB - To determine whether structural factors interact with the perception of musical time, musically literate listeners were presented repeatedly with eight-bar musical excerpts, realized with physically regular timing on an electronic piano. On each trial, one or two randomly chosen time intervals were lengthened by a small amount, and the score. The resulting detection accuracy profile across all positions in each musical excerpt showed pronounced dips in places where lengthening would typically occur in an expressive (temporally modulated) performance. False alarm percentages indicated that certain tones seemed longer a priori, and these were among the ones whose actual lengthening was easiest to detect. The detection accuracy and false alarm profiles were significantly correlated with each other and with the temporal microstructure of expert performances, as measured from sound recordings by famous artists. Thus the detection task apparently tapped into listeners' musical thought and revealed their expectations about the temporal microstructure of music performance. These expectations, like the timing patterns of actual performances, derive from the cognitive representation of musical structure, as cued by a variety of systemic factors (grouping, meter, harmonic progression) and their acoustic correlates. No simple psycho-acoustic explanation of the detection accuracy profiles was evident. The results suggest that the perception of musical time is not veridical but "warped" by the structural representation. This warping may provide a natural basis for performance evaluation: expected timing patterns sound more or less regular, unexpected ones irregular. Parallels to language performance and perception are noted. PMID- 1424495 TI - A theory of the child's theory of mind. PMID- 1424496 TI - Children's judgments in theory choice tasks: scientific rationality in childhood. AB - The current research examined whether children could use certain metaconceptual criteria such as the range of explanation, non-ad hocness of explanation, empirical consistency, and logical consistency to choose between competing accounts of physical phenomena. The tasks were constructed so that the conceptual content of the explanations to be evaluated was either consistent, inconsistent, or neutral with regard to children's prior knowledge. It was found that even 7 year-olds could use metaconceptual criteria such as the range, empirical consistency, and logical consistency of theories when the theories did not violate their beliefs. However only older children (11-year-olds) showed a systematic preference for non-ad hoc theories over ad hoc ones. The findings are consistent with recent work in the philosophy of science showing that, in evaluating theoretical alternatives, scientists are influenced by their prior beliefs about the domain being considered. This research demonstrates that even young children share some of the cognitive underpinnings of scientific rationality that scientists do. PMID- 1424497 TI - Perception, ontology, and word meaning. PMID- 1424498 TI - Lexical access in the production of noun phrases. AB - In order to encode an event or a thought into language, the speaker has to access words from the mental lexicon and order them according to the rules of syntax. The present study taps into these components of language production as they proceed in time. The utterances investigated were Dutch noun phrases with a prenominal adjective (e.g., het groene huis--the green house). The results of two picture--word interference experiments showed interference effects from semantically related noun distractors, extending findings from production of single words to the production of phrases. In addition, the syntactic format of the noun phrase had an influence on the size and the time course of the semantic interference effect. On the basis of the results of these two experiments, a working model of the processes involved in the production of noun phrases is proposed. PMID- 1424499 TI - The tip-of-the-tongue phenomenon: do experimenter-presented interlopers have any effect? AB - When a person is in a tip-of-the-tongue (TOT) state, they will sometimes recall a word that is similar in sound to the word they are attempting to retrieve. Woodworth (1929) argued that these interloper words both cause and sustain TOT states, whereas Brown and McNeill (1966) suggested that they are part of the process that leads to TOT resolution. Jones and Langford (1987) and Jones (1989) explicitly presented interloper words along with definitions of words that subjects were asked to recall. They reported that interlopers that were phonologically related to the target word increased the incidence of TOTs and concluded that this supported Woodworth's position. In three experiments, we adopted the interloper paradigm, but also included a control group who heard the definitions without interloper words. In Experiment 1, the definitions that Jones used with phonological interlopers created more TOTs even when no interlopers were presented. In Experiments 2a and 2b, we matched definitions for the number of TOTs they produced in the absence of interlopers. Under these circumstances we found no effect of interloper words at all. We conclude that there is no evidence from this paradigm to support the idea that interloper words are involved in either the causation or resolution of TOTs. PMID- 1424500 TI - What sort of innate structure is needed to "bootstrap" into syntax? AB - The paper starts from Pinker's theory of the acquisition of phrase structure; it shows that it is possible to drop all the assumptions about innate syntactic structure from this theory. These assumptions can be replaced by assumptions about the basic structure of semantic representation available at the outset of language acquisition, without penalizing the acquisition of basic phrase structure rules. Essentially, the role played by X-bar theory in Pinker's model would be played by the (presumably innate) structure of the language of thought in the revised parallel model. Bootstrapping and semantic assimilation theories are shown to be formally very similar, though making different primitive assumptions. In their primitives, semantic assimilation theories have the advantage that they can offer an account of the origin of syntactic categories instead of postulating them as primitive. Ways of improving on the semantic assimilation version of Pinker's theory are considered, including a way of deriving the NP-VP constituent division that appears to have a better fit than Pinker's to evidence on language variation. PMID- 1424501 TI - Evaluation of C. diff.-CUBE test for detection of Clostridium difficile associated diarrhea. AB - The toxin B assay was used to evaluate C. diff.-CUBE, a new dot-immunobinding assay (DIA) for the laboratory diagnosis of Clostridium difficile-associated diarrhea. The widely used latex agglutination test was also included for comparison. Stools from 100 patients suspected of having C. difficile-associated diarrhea were tested. The toxin B assay, latex agglutination, and DIA tests were positive for 12%, 9%, and 22% of the specimens, respectively. The sensitivity, specificity, and positive and negative predictive values of the DIA test were 67%, 84%, 36%, and 95%, respectively, compared with the toxin B assay. The specificity (98%) and positive predictive value (78%) for the latex agglutination test were significantly higher than those of the DIA test. Of 13 specimens solely positive by the DIA test, 11 were cultured and none were positive. Clinical assessment supported only two of the 13 positive DIA results. When clinical assessment was included in the analysis, the DIA positive predictive value rose to 45%. Although the sensitivity and negative predictive values of the DIA test are comparable to the latex agglutination test, the low specificity and positive predictive values of the DIA test make it an inappropriate method to use for screening in a population with a low prevalence of true positives. PMID- 1424502 TI - Comparison of standard and quantitative blood cultures in the evaluation of children with suspected central venous line sepsis. AB - We reviewed our experience with paired quantitative and standard blood cultures in the evaluation of children with suspected central-line sepsis with the hypothesis that by employing both systems we would increase our yield of pathogenic isolates. A total of 913 paired cultures were reviewed, representing 267 pathogenic isolates and 58 individual episodes of sepsis. The isolates were analyzed for recovery rates for each system and by combining both systems. The Isolator system proved to be equal to the BACTEC system for the recovery of all groups of pathogenic isolates. The combined use of both the quantitative and the standard culture systems demonstrated a statistically significant advantage (p less than 0.001) for the recovery of pathogens as compared with either system alone. The use of either system alone would have missed 15% of the total pathogenic isolates. Quantitative colony counts were helpful in identifying the line as the source of infection in 35 to 58 episodes of sepsis and were often beneficial in the clinical management central venous line infection. We recommend the use of the Isolator 1.5 ml combined with a conventional broth-bottle system in selected pediatric patients to enhance the recovery of pathogenic organisms. PMID- 1424503 TI - Evaluation of three different STb assays and comparison of enterotoxin pattern over a five-year period in Swedish porcine Escherichia coli. AB - The pig intestinal loop (PIL) assay, inhibition enzyme-linked immunosorbent assay (ELISA), and DNA hybridization assay were compared for analysis of Escherichia coli heat-stable enterotoxin b (STb) on 201 porcine E. coli strains. The DNA hybridization had a 95% correlation with the STb ELISA and was therefore chosen as the method for subsequent screening of enterotoxin genes: heat labile (LT), heat-stable a (STa), and/or STb. In contrast to the PIL assay, both the STb ELISA and DNA hybridization assays were more sensitive, reliable, reproducible, and showed good correlation with each other. Consequently, the STb ELISA is preferable for analysis of toxin preparations and screening of E. coli, whereas the DNA hybridization is better for large-scale epidemiologic screening. Escherichia coli strains (n = 437) associated with porcine diarrhea isolated in Sweden during 1989 were investigated. Of the strains, 135 (31%) were positive for at least one of these toxins and, therefore, designated enterotoxigenic E. coli (ETEC). Our results were compared with the enterotoxin pattern found in earlier studies of Swedish porcine strains. The only change in occurrence of toxins was found in strains isolated from piglets less than 1 week of age. LT- and STb producing ETEC had decreased, and STa-producing ETEC had increased in prevalence. The occurrence of STb among ETEC of weaned pigs was 93%. This toxin was also found to be more common than STa when strains from all age groups were considered. PMID- 1424504 TI - Rapid identification of motile Aeromonas. AB - The clinical relevance and taxonomy of motile Aeromonas species are areas of current controversy. Strains of motile Aeromonas isolates (n = 60) from various sources were identified to species level using the following tests (all incubated at 30 degrees and 37 degrees C): esculin hydrolysis; formation of gas from glucose; production of acetoin; production of acid from mannitol and arabinose; decarboxylation of lysine and ornithine, dihydrolation of arginine; and pyrazinamide hydrolysis in a semisolid medium. The tests' results were similar at incubation temperatures of 30 degrees and 37 degrees C. Of the strains, 59 (98%) of 60 were identified to species level by the full battery of tests: 25 as A. hydrophila, 18 as A. caviae, 14 as A. sobria, one as A. veronii, and one as A. schubertii. (The only A. veronii and A. schubertii isolates identified were ATCC strains). All (25 of 25) strains of A. hydrophila and 17 (94%) of 18 of A. caviae hydrolyzed pyrazinamide in less than 24 hr, whereas all strains of A. sobria showed no pyrazinamidase activity. Absence of pyrazinamidase was, thus, a convenient phenotypic marker for A. sobria. Four additional tests (esculin hydrolysis, acetoin production, lysine decarboxylation, and gas production from glucose) identified within 24 hr all examples of the three common species of Aeromonas. Recently proposed species did not contribute to our ability to discriminate among stool, other clinical, and environmental isolates of Aeromonas spp. PMID- 1424505 TI - High pentamidine levels associated with hypoglycemia and azotemia in a patient with Pneumocystis carinii pneumonia. AB - We report on a patient who presented with a Pneumocystis carinii pneumonia. Intravenous pentamidine (4 mg/kg/day) was given for 14 days without the occurrence of adverse effects. During this treatment, the mean (+/- SD) serum pentamidine trough concentration was 94 +/- 16 ng/ml. Three days later, the patient was admitted because of fever, and pentamidine (4 mg/kg/day) was again started. Fasting hypoglycemia and azotemia then occurred; the mean serum trough pentamidine level was 190 +/- 10 ng/ml during this week of treatment. We conclude that the occurrence of hypoglycemia and azotemia during pentamidine therapy may not be idiosyncrasic, but seemed associated in our patient with high levels of serum pentamidine. PMID- 1424506 TI - Acquisition of coccidioidomycosis at necropsy by inhalation of coccidioidal endospores. AB - Coccidioidomycosis is accepted as being noncontagious because the infectious arthroconidial form of Coccidioides immitis is not produced in humans and other mammalian hosts. However, disseminated coccidioidomycosis developed in a veterinarian who autopsied a horse with disseminated disease but without draining lesions or productive cough. We postulate transmission occurred by inhalation of tissue-phase endospores aerosolized in the course of dissection. PMID- 1424507 TI - Cefdinir (FK482), an orally administered cephalosporin in vitro activity comparison against recent clinical isolates from five medical centers and determination of MIC quality control guidelines. AB - Cefdinir, a new oral cephalosporin, was compared to cefaclor, cefadroxil, cefixime, and cefuroxime against greater than 5000 recent aerobic clinical isolates. This multicenter study revealed broad-spectrum cefdinir activity against all Enterobacteriaceae (MIC50s, 0.06-2 micrograms/ml) except Enterobacter cloacae, Morganella morganii, Proteus vulgaris, and Serratia marcescens (MIC50s, greater than or equal to 4 micrograms/ml). Oxacillin-susceptible staphylococci (MIC90s, 0.5-2 micrograms/ml), beta-hemolytic Streptococcus group B (MIC90, 0.06 micrograms/ml), and Acinetobacter lwoffii were also susceptible to cefdinir. The activity of cefdinir was similar to that of cefixime and cefuroxime against Gram negative organisms and superior to all tested oral cephems when tested against Gram-positive cocci. None of the cephalosporins were active against oxacillin resistant Staphylococcus spp., enterococci, Pseudomonas spp., or Xanthomonas maltophilia. MIC quality control range guidelines were established for the strains recommended by the National Committee for Clinical Laboratory Standards documents. PMID- 1424508 TI - Persistence of the same Candida albicans strain despite fluconazole therapy. Documentation by pulsed-field gel electrophoresis. AB - Candida albicans and other Candida species have emerged as major nosocomial pathogens associated with a high mortality. Therapeutic options for fungal infections are limited. Amphotericin B has been the mainstay of treatment for serious systemic candidal infections, but it is relatively toxic and associated with a variety of side effects. Fluconazole has been proposed as alternative therapy for the treatment of systemic candidiasis including candidemia. We report the case of a patient with fungemia in whom fluconazole failed to eradicate C. albicans and C. tropicalis. These pathogens were recovered from sputum and urine cultures, respectively, on day 12 of intravenous fluconazole therapy. Molecular epidemiologic techniques employing pulsed-field gel electrophoresis confirmed the persistence of the same C. albicans strain. Susceptibility studies showed a marked change in MICs of fluconazole between 24 and 48 hr, with an increase from less than or equal to 1.25 to greater than 80 micrograms/ml. Controlled trials will be needed to delineate the role of fluconazole in the treatment of disseminated candidiasis and its efficacy in comparison with amphotericin B. Amphotericin B should remain the drug of choice for such infections until data from controlled trials are available. PMID- 1424509 TI - The activity of metal compounds against aerobic and anaerobic bacteria. AB - We evaluated the antimicrobial activity of two metal compounds, JM-1397 (OsO2[xylyl]2) and JM-2469 (AuCl[S2CPEt3]). Both inhibited methicillin susceptible and methicillin-resistant Staphylococcus aureus at concentrations of 0.5-2 micrograms/ml, with a minimum inhibitory concentration (MIC90) of 1 microgram/ml for JM-1397 and 0.5 microgram/ml for JM-2469. Similar concentrations inhibited methicillin-susceptible and -resistant coagulase-negative staphylococci (S. epidermidis, S. haemolyticus, and S. saprophyticus). JM-2469 inhibited group A, B, C, F, and G beta-hemolytic streptococci and viridans group streptococci at 1-8 micrograms/ml (MIC90 4 micrograms/ml) but Enterococcus faecalis and E. faecium had MICs of 8-16 micrograms/ml. JM-1397 had MICs for these organisms of greater than 64 micrograms/ml. Bacteroides fragilis, other Bacteroides, and Clostridium species were inhibited by less than or equal to 0.12-4 micrograms/ml (MIC90, 0.5 microgram/ml). MICs of both compounds for Enterobacteriaceae and Pseudomonas spp. were greater than 64 micrograms/ml. These studies show that osmium and gold compounds have potential as topical agents against Gram-positive and anaerobic species. PMID- 1424510 TI - Vertical transmission of human immunodeficiency virus type 1. Prognostic value of IgA antibody to HIV-1 polypeptides during pregnancy. AB - In a retrospective study of 31 pregnant women infected with human immunodeficiency virus type 1 (HIV-1), nine (29%) infants presented unequivocal signs of HIV-1 infection (persistent p24 antigenemia and/or positive virus isolation). All serum samples obtained from the others, during pregnancy and on delivery, were studied for specific antibody (IgA) production by immunoblotting analysis to establish a possible link between the presence of a defined antibody class and mother-to-child viral transmission. The majority (16 of 22) of HIV-1 seropositive mothers who delivered uninfected children showed IgA antibody to low molecular-weight HIV-1 polypeptides during pregnancy. Among those who delivered infected babies, only one showed a weak IgA reactivity to HIV-1 during pregnancy. Thus, our results suggest that immunoblotting study of IgA may be a diagnostic adjunct to predict the risk of mother-to-child HIV-1 transmission. PMID- 1424511 TI - Copepods associated with a perirectal abscess and copepod pseudo-outbreaks in stools for ova and parasite examinations. AB - We observed copepods, an intermediate host for several human parasites, in material obtained from a perirectal abscess of a 22-year-old man with Crohn's disease. We subsequently noted copepod "outbreaks" in stool specimens submitted for ova and parasite examination. Copepods in the hospital tap water supply were the source for one "outbreak". PMID- 1424512 TI - Evaluation of an improved DNA probe for diagnosis of pertussis. AB - A Bordetella pertussis specific subclone, pRZ61, of a Bordetella genus-specific clone, pB23, was evaluated on nasopharyngeal aspirates of 179 patients with suspected pertussis. Hybridization was performed directly after spotting or after 1-3 days of preculture of the nylon membranes on solid culture medium. A direct comparison of the two probes was obtained by reprobing with the subclone the same membranes that had been hybridized with the parent probe. pRZ61 detected 50% of the serologically defined cases of pertussis, that is, had the same sensitivity as standard culture. Specificity as compared with serology was close to 100%. The increasing sensitivity and the corresponding decreasing specificity after preculture noted for pB23 was not seen with the subclone. The study showed that the improved probe represents a rapid diagnostic method in pertussis. PMID- 1424513 TI - Catheter-related bacteremia and fungemia. Reliability of two methods for catheter culture. AB - The purpose of this study was to analyze 98 febrile patients with suspected catheter-related bacteremia (CRB) or fungemia (CRF) and compare two different methods, one semiquantitative (SQ) (Maki's method) and the other quantitative (Q) (modification of Brun-Buisson method) to determine each ability for diagnosing CRB. Twelve patients had CRB or CRF. The sensitivity, specificity, positive, and negative predictive values, and efficiency using the Maki method were 83%, 84%, 42%, 97%, and 83%, respectively. The same parameters using the other method were as follows: 92%, 84%, 44%, 99%, and 84%, respectively. Although the diagnostic reliability in each method was similar, the Maki method was quicker and easier to perform in clinical microbiology laboratories. PMID- 1424514 TI - Evaluation of two ELISA's for detecting Chlamydia trachomatis from endocervical swabs. AB - Two enzyme immunoassays (EIAs) detecting Chlamydia trachomatis from endocervical swabs, Syva MicroTrak (MT) and Abbott Chlamydiazyme (CZ), were compared with a tissue culture (TC) standard. Initially, 8% (100 of 1250) of specimens were TC positive, yielding sensitivities of 94% (94 of 100) for MT and 79% (79 of 100) for CZ with identical 98% specificities (1129 of 1150 for MT and 1130 of 1150 for CZ). Discrepant specimens were retested by both EIAs and assayed for elementary bodies (EBs) by a fluorescent antibody test. After discrepancy analysis, 9.5% (118) of 1240 patients were either TC or EB positive, yielding sensitivities of 94.1% for MT (111 of 118) and 79.7% for CZ (94 of 118) with identical specificities of 100% (1122 of 1122). These results indicate that the MT is significantly more sensitive (p less than 0.05, McNemar test) than CZ in detecting C. trachomatis from endocervical swabs. PMID- 1424515 TI - Performance characteristics of a commercial antibody-capture enzyme immunoassay for detection of Toxoplasma-specific IgM antibodies. AB - Antibody-capture enzyme immunoassay (EIA) for the detection of Toxoplasma specific IgM has been shown to provide significantly higher specificity than the indirect IgM EIA. A new commercially available antibody-capture EIA (PLATELIA Toxo IgM EIA) converted 99 out of 100 false-positive Toxo-plasma IgM determinations to true negative. Experiments using Toxoplasma IgM calibrators demonstrated the antibody-capture EIA is approximately eightfold more sensitive than a new automated microparticle EIA for Toxoplasma IgM antibodies (IMX Toxo IgM EIA), and approximately equal in sensitivity to the indirect immunofluorescence assay. Precision studies of the antibody capture EIA using low, medium, and high calibrators gave coefficients of variation ranging from 3.0%-4.5% for within-run and 5.2%-11.4% for run-to-run variation experiments. Interference from high levels of bilirubin, albumin, hemoglobin, and lipid was not detected. Sera from patients with inflammatory or infectious disorders were tested for interference in the antibody-capture EIA. False-positive Toxoplasma IgM results were not observed, but low-level negative interference was detectable when patient sera was mixed with Toxoplasma-positive sera. Preparations of purified human IgM also produced negative interference in the antibody-capture EIA for Toxoplasma IgM. PMID- 1424516 TI - Lack of predictability of cefotetan in vitro susceptibility tests against cefotetan-resistant anaerobic bacteria in determining clinical and bacteriologic efficacies. AB - Interpretive criteria for cefotetan in vitro susceptibility testing appear to be clinically relevant when applied to aerobic bacteria. To determine whether the same was true for anaerobic bacteria, we conducted a retrospective analysis of intraabdominal, gynecologic, and skin and skin structure infections treated with cefotetan. Of the infections, 202 contained at least one anaerobe isolate. Of the 51 patients, 47 (92.9%) from whom one or more cefotetan-resistant anaerobes were isolated were clinically cured or showed improvement. Similarly, cefotetan was efficacious for 95.4% of the patients harboring only cefotetan-susceptible anaerobes. Favorable bacteriologic responses were observed in 94.1% and 97.4% of these patient groups, respectively. The data suggests that the therapeutic utility of cefotetan against anaerobic bacteria cannot be accurately predicted on the basis of in vitro susceptibility test results alone but may be explained by a variety of factors, as discussed in this report. PMID- 1424517 TI - The rapid emergence of fluoroquinolone-methicillin-resistant Staphylococcus aureus infections in a community hospital. An in vitro look at alternative antimicrobial agents. AB - The introduction of ciprofloxacin on an unrestricted basis into a 900-bed community hospital resulted in the emergence of high-level fluoroquinolone resistance among methicillin-resistant Staphylococcus aureus (MRSA) during the subsequent 18 months. Susceptibility testing revealed several old and new compounds to which all the S. aureus strains were susceptible. When an MRSA strain became resistant to ciprofloxacin it also exhibited high-level resistance to ofloxacin, fleroxacin, norfloxacin, and enoxacin. Two new experimental fluoroquinolones, WIN 57273 and CI-960, exhibited good activity against all test strains. Among the glycopeptide compounds, mupirocin and teicoplanin were approximately fourfold more active than vancomycin and ramoplanin. Rifampin and trimethoprim-sulfamethoxazole (TMP/SMZ) showed good activity against most strains as did imipenem. For clindamycin, gentamicin, and tetracycline susceptibilities exhibited a bimodal distribution with at least 10% of strains having resistant MIC values. Surprisingly, the addition of sulbactam potentiated the activity of ampicillin against the ciprofloxacin-resistant MRSA strains, however, sulbactam had little effect on cefoperazone activity against these same strains. Time-kill kinetic studies of selected antimicrobials against ciprofloxacin-resistant strains indicated good killing by vancomycin, ampicillin-sulbactam, and TMP/SMZ. Teicoplanin was less bactericidal than vancomycin while these same strains rapidly developed resistance to rifampin even at concentrations 8 x MIC. These data indicate certain alternative compounds within our study warrant further investigation, especially in vivo, against multiply-resistant staphylococci. PMID- 1424518 TI - Evaluation of the teicoplanin broth microdilution and disk diffusion susceptibility tests and recommended interpretive criteria. AB - Comparative teicoplanin in vitro susceptibility data were generated for 1201 Gram positive US clinical trial isolates using standardized broth microdilution and disk diffusion techniques. Based on the results of this study, the following interpretive criteria for teicoplanin are recommended: for MIC tests, less than or equal to 8 micrograms/ml = susceptible, 16 micrograms/ml = moderately susceptible, and greater than or equal to 32 micrograms/ml = resistant; and for disk (30 micrograms) tests, greater than or equal to 14 mm = susceptible, 11-13 mm = intermediate, and less than or equal to 10 mm = resistant. PMID- 1424519 TI - Antibacterial oxazolidinones. In vitro activity of a new analogue, E3709. AB - The oxazolidinone compound E3709, which contains a 4-pyridyl group, was found to be more active in vitro than other members of this series, such as DuP 721. MIC90 for staphylococci(including methicillin-resistant isolates), streptococci (including Enterococcus faecalis), Clostridia, and diphtheroids was less than 0.5 micrograms/ml. Haemophilus influenzae, Moraxella catarrhalis, and Bacteroides fragilis were less susceptible, with an MIC90 between 2 and 8 micrograms/ml. E3709 MICs of Gram-negative species ranged from 100 to greater than 1000 micrograms/ml. At a concentration of 10 micrograms/ml, E3709 was bactericidal for selected Gram-positive species. A postantibiotic effect of 3 hr was observed against staphylococci. Resistance to E3709 was not detected. PMID- 1424520 TI - Cefmetazole and trospectomycin in vitro susceptibility testing interpretive criteria and quality control guidelines for Neisseria gonorrheae. AB - Cefmetazole and trospectomycin were tested in a multilaboratory trial to establish Neisseria gonorrhoeae susceptibility testing criteria and quality control (QC) guidelines. Cefmetazole was active against the penicillinase producing isolates and has an MIC90 of 16 micrograms/ml, the breakpoint MIC previously used for nonfastidious species. However, a single-dose gonorrhea regimen (1 g i.m.) would require a lower less than or equal to 2 micrograms/ml breakpoint with a correlate zone (greater than or equal to 33 mm) consistent with similarly used cephamycins (cefoxitin and cefotetan). An intermediate category was proposed for MICs greater than 2-4 micrograms/m (28-32 mm) pending more clinical experience with higher and/or prolonged cefmetazole dosing regimens. Trospectomycin was active (MIC90, 8 micrograms/ml) against all spectinomycin susceptible gonococci. A susceptible breakpoint MIC of less than or equal to 16 micrograms trospectomycin per milliliter was proposed with a correlate zone diameter of greater than or equal to 17 mm. An intermediate category was also suggested for trospectomycin at 32 micrograms/ml (14-16 mm). QC guidelines were established for 30-micrograms cefmetazole and 30-micrograms trospectomycin disk diffusion tests and the GC agar base MICs using a multilaboratory study design consistent with National Committee for Clinical Laboratory Standards (NCCLS) M23 T guidelines. Both drugs were stable in GC agar plates for 21 days stored at 2 degrees-5 degrees C. PMID- 1424521 TI - In vitro activity of cefprozil (BMY 28100) and cefepime (BMY 28142) against Streptococcus pneumoniae, Branhamella catarrhalis, and Haemophilus influenzae, and provisional interpretive criteria for disk diffusion and dilution susceptibility tests with Haemophilus influenzae. AB - The in vitro activities of two new cephalosporins, an oral agent, cefprozil and a parenteral compound, cefepime, were assessed against recent clinical isolates of Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, and Haemophilus influenzae. In general, both cefprozil and cefepime MICs were higher for beta lactamase-producing strains of M. catarrhalis in comparison to strains that lacked beta-lactamase. By contrast, beta-lactamase-positive and -negative strains of H. influenzae had similar cefprozil and cefepime minimum inhibitory concentrations (MICs). The MIC90 values for cefprozil were 0.12, 32, 4.0, and 0.5 micrograms/ml versus S. pneumoniae, H. influenzae, and beta-lactamase-positive and negative strains of M. catarrhalis, respectively. In comparison to three other oral cephalosporins included in this study, cefaclor, cefuroxime axetil, and cefixime, cefprozil was the most active agent against S. pneumoniae, the least active against B. catarrhalis, and equivalent in activity to cefaclor against H. influenzae. The cefepime MIC values against S. pneumoniae, H. influenzae, and beta-lactamase-positive and negative strains of M. catarrhalis were 0.03, 0.25, 2.0, and 0.5 micrograms/ml, respectively. Cefepime was less active than ceftriaxone for all three organism groups, however, was in all cases more active than cefixime, cefuroxime, cefaclor, and cefprozil.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424522 TI - In vitro activity of mersacidin (M87-1551), an investigational peptide antibiotic tested against gram-positive bloodstream isolates. AB - We measured the in vitro activity of mersacidin (formerly M87-1551) against 183 clinical isolates (vancomycin susceptible) and 12 additional vancomycin-resistant strains of Gram-positive bacteria. The activity for mersacidin increased an average twofold (range, 1.7- to 7.6-fold) in a calcium-enriched medium. The minimum inhibitory concentration (MIC)90 for mersacidin was 8-32 times higher than vancomycin for staphylococci, 4-64 times higher for enterococci, and up to 32 times higher for other organisms tested. The MIC90 for MDL 62873, a comparison compound, was less than or equal to 0.5 micrograms/ml for all species except Staphylococcus haemolyticus (MIC90, 4 micrograms/ml), and it was greater than or equal to 4-fold more active than vancomycin. Against selected vancomycin resistant strains, mersacidin had MICs greater than or equal to 16 micrograms/ml for enterococci, 4-32 micrograms/ml for Pediococcus, and less than or equal to 2 micrograms/ml for Leuconostoc species. Mersacidin may have some clinical utility in documented infections caused by staphylococci, nonenteric streptococci, Pediococcus, and Leuconostoc. PMID- 1424524 TI - Cardiac transplantation: future directions. PMID- 1424523 TI - Ventricular/vascular interaction in health and heart failure. AB - In summary, the concept of aortic input impedance, which has been examined in detail, requires evaluation of the flow and pressure pulsations within the ascending aorta to determine an input impedance spectrum. This function describes the load imposed on the ejecting left ventricle by the systemic vasculature in terms of pulsatile and steady-flow components and is independent of changes in ventricular performance. The components contain information about the mechanical properties of the large vessels (elastance), arteriolar bed (resistance), and waves reflected (reflectance) within the arterial system. Our investigations indicate that in health the mechanical characteristics of the vasculature appear to minimize pulsatile and steady-flow loading components. The optimal loading pattern is influenced by aging and hypertension so that elastance is increased. This alteration increases the pulsatile flow component of loading, which has the potential to limit left ventricular responses to exercise. In patients with heart failure, the vascular system presents an increase in pulsatile and steady-flow load to the diseased left ventricle. Here the altered loading pattern is due to increased resistance, elastance, and reflectance. The left ventricle has a markedly diminished response to power output in the face of this altered vascular load. With vasorelaxation, all components of vascular loading decrease and result in markedly improved generation of left ventricular power and cardiac output. Recent evidence suggests that agents inducing vasorelaxation can influence various regions of the aorta and large vascular beds in a different manner. This would result in the ability to alter elastance, resistance, and reflectance selectively to affect pulsatile and steady-flow components of load.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424526 TI - Renovascular hypertension: pathophysiology, diagnosis, and therapeutic options. PMID- 1424525 TI - Acute myocardial infarction: early diagnosis and indications for thrombolysis. PMID- 1424527 TI - Percutaneous balloon valvotomy for mitral stenosis. PMID- 1424529 TI - Cushing's syndrome. PMID- 1424528 TI - Risk factors in the pathogenesis of coronary artery disease. PMID- 1424530 TI - Evaluation and treatment of swallowing disorders. PMID- 1424531 TI - Inflammatory bowel disease: family patterns and risk factors. PMID- 1424532 TI - Evaluation of patients for liver transplantation. PMID- 1424533 TI - Short gut syndrome--options for management. PMID- 1424534 TI - Tretinoin (Retin-A) therapy of photoaged skin. PMID- 1424535 TI - Clinical evaluation of generalized pruritus. PMID- 1424536 TI - Sports related skin problems. PMID- 1424537 TI - Behcet's disease: now you see it, now you don't. PMID- 1424538 TI - Applications of lasers for skin disorders. PMID- 1424539 TI - Cutaneous manifestations of systemic diseases. PMID- 1424540 TI - Use of fluoride tablets and effect on prevalence of dental caries and dental fluorosis. AB - A study was executed to investigate the relation between the use of fluoride tablets by children in the age period 1.5-6 yr on the one hand and the caries experience at the age of 6 and 15 yr and the prevalence of fluorosis at the age of 15 yr on the other hand. The year of birth of the child, the motivation of the mother to engage in preventive dental behavior, the level of her school education and her place of birth were taken into account as possible confounding factors. A significant relation was found between the use of fluoride tablets and the prevalence of fluorosis. The most important predicting factor for the caries experience of the child was the mother's motivation to engage in preventive dental behavior. An effect of fluoride tablets on the caries experience could not be demonstrated. PMID- 1424541 TI - Decline in caries prevalence in 6-14-year-old schoolchildren during 1975-85 in Shizuoka, Japan. AB - The purpose of this study was to examine changes in caries prevalence during 1975 85 in Japanese schoolchildren who did not have an apparent change in fluoride exposure. A total of 2872 schoolchildren aged 6-14 yr in two primary schools and one junior high school in Shizuoka city, Japan, were examined in 1985. The caries prevalence in 1985 was then compared with data which had been collected in a longitudinal survey on schoolchildren in the same primary and junior high schools by Katayama in 1970-75. The results indicated that DMFT and DMFS indices in 1985 were significantly lower than those in 1970-75 in all the examined ages (P < 0.01). The DMFT indices at age 12 were 3.60 in 1985 and 5.47 in 1970-75. Remarkable decreases in DMFT at age 12 were observed in maxillary incisors (50%), followed by maxillary molars (24%) and mandibular molars (22%). The decline in caries prevalence in the examined area may be mainly attributed to several factors other than use of fluoride, such as changes in dietary pattern, an increasing dental awareness and promotion of dental health care. But the percentage decrease per annum of DMFT index at age of 12 in the examined population was relatively low (-4.1%) in comparison with other industrial countries. Comparing the results with data from national dental surveys, it can be considered that rural areas in Japan do not exhibit a similar decline of caries prevalence as in Shizuoka city, but there will be a lot of districts exhibiting significant reduction in caries prevalence in the near future. PMID- 1424542 TI - Prevalence of non-cavitated and cavitated carious lesions in a random sample of 7 9-year-old schoolchildren in Montreal, Quebec. AB - This report describes the prevalence of non-cavitated and cavitated carious lesions in 911 randomly selected children in grades one through three on the Island of Montreal, Quebec, Canada. The criteria for diagnosis were developed for a longitudinal epidemiological study of restorative treatment decisions by dentists practising under a provincial dental insurance program for children. The intra- and inter-examiner reliability correlation coefficients of the two examiners were excellent (Kappa > or = 0.80). The most frequent carious lesion found in the examined children were non-cavitated carious lesions (incipient) within 1.5 of the gingival line on smooth tooth surfaces, and stained or non cavitated carious lesions on pits and fissures. Out of 911 children in the study, 19.6% had sealants. Children whose parents completed a university education had a significantly lower prevalence of non-cavitated and cavitated carious lesions and fillings, and a significantly higher mean number of sealants than children whose parents had only primary school education. Education status of the parents was a significant risk marker of children with high caries experience and these children had a significantly higher mean number of non-cavitated carious lesions. This study has found that non-cavitated carious lesions are significantly more prevalent than cavitated carious lesions in children. PMID- 1424543 TI - Risk indicators and potential risk factors for caries in 5-year-olds of different ethnic groups in Amsterdam. AB - The aim of this study was threefold: first, to assess the oral health of Turkish, Moroccan, Surinamese, Dutch and "other" 5-yr-old children living in Amsterdam; second, to identify risk indicators for caries, in addition to ethnicity; and third, to identify potential risk factors related to differences in caries experience in these children. Results showed the mean dmfs scores of Turkish and Moroccan children to be much higher than that of the Dutch and Surinamese children; 8.1 and 8.2 versus 3.6 and 3.4, respectively. The educational level of the parents and the gender of the children were important risk indicators, in addition to ethnicity. The age of the child at which the parents had started to brush their child's teeth, the use of fluoride tablets and the regularity of the brushing behavior in the past could be identified as potential risk factors. PMID- 1424544 TI - Relationship of microbial and salivary parameters with dental caries in Brazilian pre-school children. AB - Caries examination and collection of paraffin wax-stimulated saliva samples were performed in 37 children, 3-6 years old, in a child-care facility at the Vidigal slum, Rio de Janeiro, Brazil. The levels of mutans streptococci and lactobacilli in saliva were estimated by the Cariescreen and by the Dentocult tests and the saliva secretion rate was determined. Statistical analysis was performed on surface-based and patient-based caries prevalence rates (SBCPR and PBCPR), and related to bacterial and salivary parameters. The results show that 31 of the 37 children were caries active. The SBCPR for the primary dentition was 6.7% +/- 1.0%. Occlusal surfaces were the most affected by decay. Regression analysis revealed that mutans streptococci salivary levels were significantly associated with the SBCPR (P = 0.0001). Similarly, lactobacilli salivary levels were significantly associated with the SBCPR (P = 0.0001). No significant association could be found between the saliva secretion rate and the SBCPR. When regression analysis was used to model dependence of the SBCPR on both organisms, the mutans streptococci and lactobacilli salivary levels were significantly associated with the SBCPRs (P = 0.0021 and 0.0118, respectively), and salivary levels of these organisms accounted for 57% of the SBCPR variability. These findings indicate that the levels of mutans streptococci and lactobacilli in saliva are significantly related to the SBCPRs on the primary dentition of these children. PMID- 1424545 TI - Restorative treatment thresholds and agreement in treatment decision-making. AB - It has been recognised for many years that treatment decision-making among dentists often shows wide variation. This study sought to examine the effect of dentists' stated treatment thresholds as a source of variation between them. Twenty dentists made 360 treatment decisions about the approximal surface of extracted teeth seen in simulated bitewing radiographs. They also stated their personal treatment thresholds, i.e. the depth of lesion which they intended to restore. One hundred and ninety pairwise comparisons of treatment decisions showed that only 16% of the dentist pairs showed substantial agreement. Dentist pairs who reported that they held the same interventive threshold achieved exactly the same mean level of agreement in treatment decision-making as dentist pairs who disagreed about the appropriate threshold for restorative intervention. The study suggests that restorative thresholds which are reported to be used by dentists may be poorly correlated with the number of positive treatment decisions actually made. PMID- 1424546 TI - Assessment of dental health state utilities. AB - The term "health state utility" implies the assigning of a numerical value to a state of health. Assessment of the success of health care procedures, using health state utilities, enables evaluation of available treatments and procedures in terms of differing health outcomes and therefore facilitates cost-benefit analyses. Although measurement of general health state utilities has become increasingly common in medicine using a variety of techniques, few attempts have as yet been made in dentistry to place valuations on different dental health states. The absence of tried and tested methods for measuring tooth quality make the benefits gained from preventive and restorative dental programmes difficult to quantify. The aim of this study was to assess the average utility values, held by a group of dentists and a group of members of the general public, for four different tooth states which it was hypothesised would have different values. These were 1) a decayed and painful posterior tooth; 2) a decayed and non-painful posterior tooth; 3) a posterior tooth which had been restored and would need further restorative treatment and 4) a permanently restored posterior tooth. A standard gamble questionnaire was used to elicit the utility values which were then substituted as "weightings" in a modified version of the "T-health" index (1). The results show that it is possible to assess dental health state utility values using the standard gamble method and that the average utility values of the dentists in the study were consistently higher than those of the general public.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424547 TI - A new Norwegian index of orthodontic treatment need related to orthodontic concern among 11-year-olds and their parents. AB - A new index of orthodontic treatment need was introduced in Norway in 1990. On a morphologic and functional basis the four groups very great (A), great (B), obvious (C) and little/no (D) need were defined for social insurance refunding. The purpose of the present study was to investigate to what extent the new index corresponded with orthodontic concern among potential orthodontic patients and their parents. Of 104 randomly selected fourth grade children, 99 (48 girls, 51 boys, mean age 10.7 yr) presented themselves for clinical examination and interview. One parent was asked to accompany the child, and 93 parents attended. On the basis of clinical examination, morphologic measurements on study casts, and X-rays, the children were allocated to one of the four groups defined by the index. In separate questionnaires the children and the parents were asked to assess satisfaction with own/child's dental arrangement and desire for orthodontic treatment. The interview data were transformed into a composite measure representing orthodontic concern. The results indicated that orthodontic concern was significantly related to index group. For the individuals who expressed concern the new index seemed to be meaningful for allocation of public subsidies, as most individuals (85%) who expressed concern exhibited malocclusions fulfilling the criteria for receiving public subsidies of treatment costs. However, more than 50% of the individuals allocated to group B (great need) did not experience a need for treatment. PMID- 1424548 TI - A method to compare cost-effectiveness of dental treatments: adhesive bridges compared to conventional bridges. AB - The cost-effectiveness of a dental restoration depends primarily on the durability and the cost of the restoration. In this report a method is described to compare the cost-effectiveness using the durability data of adhesive bridges and conventional bridges. The study shows that, for the situation in the Netherlands, the breakeven point for equal cost-effectiveness compared to conventional bridges is achieved when the 50% survival for adhesive bridges is approximately 6.5 yr. Clinical data indicate a higher cost-effectiveness for anterior adhesive bridges. The method described in this report is considered to be useful for comparing cost-effectiveness of dental restorations in different situations. PMID- 1424549 TI - Coefficients of relationship by isonymy among oral cancer registrations in Scottish males. AB - The role of inherited susceptibility to oral cancers was studied by comparing groups of cancer patients and controls in terms of the coefficient of relationship by isonymy (Ri), both within and between Regions of mainland Scotland. Surname distributions for 3658 male cancer cases were derived from the Scottish Cancer Register for the years 1959-85. Control distributions were derived from a total of 32,468 male deaths in Scotland for 1976. For cancer of the floor of mouth, there was no evidence for increased isonymy in patients compared to controls and therefore no indication that familial factors contribute to cancer at this site. For cancer of the tongue there was a suggestion of increased isonymy within but not between Regions, perhaps reflecting environmental risk factors common to members of the same family. For cancers of the lip and salivary gland there was evidence of increased isonymy both within and to a lesser extent between Regions, suggesting a genetic contribution. There is corroborative evidence from other sources for a heritable component in salivary gland cancer but the reasons for the similar pattern of results in cancer of the lip are less clear. PMID- 1424550 TI - Incidence and severity of phenytoin-induced gingival overgrowth in epileptic patients in general medical practice. AB - This investigation examines the incidence of phenytoin-induced gingival overgrowth in a population of epileptic patients who attend General Medical Practices for treatment of their epilepsy and compares the gingival changes with an otherwise healthy group of patients. The plaque score, gingival index, and gingival overgrowth did not differ significantly between the two groups (P > 0.05). A significant correlation was observed between plaque score and gingival overgrowth in the phenytoin-treated patient, but in this group there was no correlation between gingival overgrowth and salivary concentration of the drug. The overall incidence of clinically significant overgrowth (13%) is considerably less than in other studies. PMID- 1424551 TI - Remaining teeth, oral dryness and dental health habits in middle-aged Norwegian rheumatoid arthritis patients. AB - The aim of the study was to assess the effect of rheumatoid arthritis (RA) upon dental health. A questionnaire was mailed to all seropositive rheumatoid arthritis (RA) patients aged 44-56 yr in the files of the two main departments of rheumatology in South Eastern Norway. Data were obtained from 125 patients, constituting 91% of the target group. The number of remaining teeth in these patients was not related to disease duration or physical dysfunction, whereas a relationship to prolonged use of medication for pain relief was indicated. Factors known to affect tooth loss in the general population, such as smoking habits, dental attendance, interdental cleaning habits, previous dental disease, and place of residence were found to be important in RA patients as well. The RA patients from Oslo had a mean number of 25 remaining teeth, which is the same as reported for the general Oslo population at this age. Oral dryness was reported by more than 50% of the RA patients, but was not related to the number of teeth. The conclusion is that serious and long lasting rheumatoid arthritis had little influence on the number of remaining teeth in this middle-aged group of Norwegians. PMID- 1424552 TI - Oral health conditions and denture treatment needs in institutionalized elderly people in Japan. AB - Oral health conditions, including dental conditions, temporomandibular joint (TMJ) conditions, denture status, and oral hygiene status, were assessed on 1908 institutionalized elderly people 65 yr of age and older at 29 of the 30 existing institutions in the city of Kitakyushu, Japan. The percentage of edentulous people was 27% in the 65-74-yr-old group, and increased with age to 56% in the 85 yr and older group. In dentate persons, the mean number of remaining teeth and DF teeth were 13.4 and 8.6, 9.5 and 6.8, and 8.4 and 6.5 in the groups aged 65-74 yr old, 75-84 yr old, and 85 yr and older, respectively. 81% of all the persons examined had no unusual symptoms in their TMJ. A clicking sound was the most frequent symptom (17%). Hygiene of both their teeth and dentures was very poor. Of all the subjects, 36% needed new full and/or partial denture(s), and 41% needed only repair. When the institutionalized elderly people were compared according to their general health condition, no clear differences were observed in percentage of edentulousness, mean number of remaining teeth and DF teeth, and TMJ conditions. However, a higher level of both untreated teeth and denture treatment needs, and poorer oral hygiene, was found in elderly people having poor general health than was observed in those with better health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424553 TI - Prognosis of overdenture abutments in the aged: effect of denture wearing habits. AB - The effect of denture wearing habits was studied in 35 overdenture wearers (20 day-and-night wearers, 15 day-wearers) during a period of 3 yr with controlled oral hygiene. Prior to prosthetic treatment intensive instruction and motivation in oral hygiene were carried out and the patients were recalled 2-4 times yearly during the study period. Before treatment mean Plaque Index (PlI) and Gingival Index (GI) were 1.5 and 1.6, respectively, in both groups of patients. At day 0, 1 yr, 2 yr and 3 yr mean PlI and GI were 0.3-0.5 and 0.6-0.8, respectively, in the group of day-wearers and 0.5-1.0 and 1.0-1.2, respectively, in the group of day-and-night wearers. This difference was statistically significant. Furthermore, during the study period 16% of the abutment tooth surfaces showed attachment loss (1-4 mm) in the group of day-and-night wearers against 7% of the tooth surfaces in the group of day-wearers. This difference was statistically significant. During the 3 yr 36 carious lesions developed in the group of day-and night wearers, but none in the group of day-wearers. The results of this study have shown that day-and-night wearing of dentures is a major periodontitis and caries risk factor in complete overdenture wearers with controlled oral hygiene. PMID- 1424554 TI - Joint epidemiological survey on dental health of 12-year-old school children in Dublin and Glasgow. PMID- 1424555 TI - Trends of caries prevalence and experience in children in Chengdu City, West China, 1982-1990. PMID- 1424556 TI - Periodontal treatment need of the Dutch 15-74-year-old population. PMID- 1424557 TI - Prevalence of recurrent caries in three adult communities in Poland. PMID- 1424558 TI - Observations on production of hemolysin, heat-labile enterotoxin and antimicrobial drug resistance among enterotoxigenic Escherichia coli from pigs. AB - A total of 52 isolates of Escherichia coli belonging to enterotoxigenic serotypes from piglets with diarrhea were examined for hemolysis, production of cholera like enterotoxin (LT) and susceptibility to 10 antimicrobial drugs. A strong association between production of LT and hemolysis was seen. Ninety percent of 29 hemolylic isolates were LT+ whereas 100% of 23 nonhemolytic isolates were LT- in a commercial latex agglutination assay. Antimicrobial susceptibility tests employing disc diffusion showed that resistance to trimethoprim-sulfamethoxazole (TMS), neomycin and tetracycline was significantly less among LT+ isolates compared to LT- ones. Enrofloxacin was the only antimicrobial drug to which all the 52 isolates were susceptible. PMID- 1424559 TI - Epidemiology of an outbreak of leptospirosis in man and dog. AB - An outbreak of leptospirosis in man and dog occurred during the monsoon in Madras city, India. 48 (50.5%) of the 95 human sera tested were positive for leptospirosis. Of these, 32 showed the presence of agglutinin to serovar icterohaemorrhagiae. 20 (21.3%) of the 94 canine sera tested were positive for leptospirosis. Of these, 10 had agglutinins to serovar icterohaemorrhagiae and 9 to serovar canicola. Among murine reservoirs, 8 (25%) of 32 rat sera and 10 (41.6%) of 24 bandicoot sera were positive. Bandicoot and rat sera contained 70 and 50% of agglutinins to serovar icterohaemorrhagiae, respectively. Urine culture lead to isolate a icterohaemorrhagiae strain from a patient and a canicola one from a dog. The changing trends of epidemiology in the transmission of leptospirosis to man and dog has been discussed. PMID- 1424560 TI - Change in interleukin 2 production by lymphocytes during maturation of young cats. AB - Lymphocytes from four specific-pathogen free cats were tested for their interleukin 2 activity every week beginning when the cats were 12 weeks old and ending when they were 26 weeks old. Lymphocytes from cats > or = 20 weeks old released significantly more interleukin 2 than those obtained from these cats at earlier ages when stimulated with calcium ionophore A23187 and phorbol myristate acetate. The change of interleukin 2 levels with maturation of young cats may represent an important difference in their level of defense to infections with various pathogens. PMID- 1424561 TI - A cytotonic, cholera toxin-like protein produced by Campylobacter jejuni. AB - 1. Campylobacter jejuni is a major cause of gastroenteric infection. 2. This organism appears to produce both cytotonic and cytotoxic virulence factors. 3. We report here that culture filtrates of some clinical isolates of C. jejuni induce elongation of Chinese hamster ovary (CHO) cells in vitro but do not cause inhibition of fluid absorption in the rat ileum. 4. These culture filtrates contain low levels of a protein which cross-reacts immunologically with the cholera toxin. 5. The cholera toxin-like protein of C. jejuni behaved identically to cholera toxin on non-denaturing polyacrylamide gel electrophoresis. 6. Under denaturing conditions, however, this protein displayed no subunit structure and a molecular weight of approximately 50 kDa with many higher molecular weight aggregates. 7. In conclusion, isolates of C. jejuni produced small amounts of enterotoxin when grown in vitro. 8. The toxin cross-reacted immunologically with cholera toxin and has a similar native structure, but does not appear to possess subunits. PMID- 1424562 TI - Isolation of lactose-binding lectins from axolotl (Ambystoma mexicanum). AB - 1. Lactose-inhibitable hemagglutination activity was identified in extracts of axolotl (Ambystoma mexicanum) larvae. 2. Two types of lectin were isolated from extracts by affinity chromatography on lactose-Sepharose. 3. A thiol-independent lectin of subunit mol. wt 15 kDa and a thiol-dependent lectin of subunit mol. wt 18 kDa were identified. 4. The 15 kDa and a 18 kDa polypeptides were weakly reactive with polyclonal anti-human galaptin serum. PMID- 1424563 TI - Enzymological studies of melanin concentrating hormone (MCH) and related analogues. AB - 1. Salmon melanin concentrating hormone (MCH) is a cyclic heptadecapeptide possessing the following primary structure: Asp-Thr-Met-Arg-Cys-Met-Val-Gly-Arg Val-Tyr-Arg-Pro-Cys-Trp-Glu-Val. 2. In the fish, Synbranchus marmoratus, skin bioassay MCH5-15 is equipotent to MCH whereas MCH5-14, which comprises only the ring structure, is about 100-fold less active. 3. MCH and two fragment analogues, MCH5-15 and MCH5-14, were studied to determine their relative stability in the presence of fish serum and purified proteolytic enzymes, trypsin and alpha chymotrypsin. 4. After 4 hr incubation in fish serum, MCH5-15 retained 1/100, MCH5-14 1/1000 and MCH only 6/1000 of the potency of the native hormone. 5. The three peptides were also very resistant to degradation by purified proteolytic enzymes involving the following relative order of resistance: MCH5-14 > MCH5-15 > MCH. MCH5-14 potency was not altered after a 1 hr incubation in either enzyme whereas MCH retained 1/10 and 4/100 of its original potency, and MCH5-15 retained 1/10 and 8/10 of its original potency, after 1 hr in trypsin and alpha chymotrypsin, respectively. PMID- 1424564 TI - Inhibitory effect of sulfhydryl group on Ca(2+)-ATPase activity in the plasma membrane-rich fraction from bovine parotid gland. AB - 1. The present study demonstrated that the Ca(2+)-ATPase activity of the plasma membrane-rich fraction from bovine parotid gland was decreased by the addition of reducing agents. 2. Ca(2+)-ATPase activity staining on SDS-PAGE gels was lost in the presence of 2-mercaptoethanol. 3. Among all the reducing agents tested, GSH was the most effective in inhibiting Ca(2+)-ATPase. 4. The Ca(2+)-ATPase activity decreased by the GSH was restored by the addition of an oxidizing reagent. However, oxidation with an oxidizing reagent subsequent to alkylation of the reduced enzyme with iodoacetamide resulted in no restoration of activity. 5. The decrease of Ca(2+)-ATPase activity by GSH is due to a decrease in the Vmax of the enzyme. 6. These results suggest that the disulfide bond in this enzyme protein is necessary to maintain the activity of this enzyme. PMID- 1424565 TI - Presence of D-aspartate oxidase and free D-aspartate in amphibian (Xenopus laevis, Cynops pyrrhogaster) tissues. AB - 1. This paper is the first report on the presence of D-aspartate oxidase activity and free D-aspartate in the amphibian tissues. 2. The presence of D-aspartate oxidase activity in tissues of clawed toad (Xenopus laevis) and Japanese newt (Cynops pyrrhogaster) was demonstrated by requirements for enzyme activity, selective inhibition with meso-tartrate and substrate specificity. 3. In each animal, the highest activity was found in kidney, followed by liver and brain, and no gender difference in the specific activity was observed in each tissue. 4. A small but significant amount of D-aspartate was detected in liver and kidney, irrespective of species. 5. In the newt, there was a gender difference in the hepatic and renal content of D-aspartate and not in the D-/D+L-aspartate ratio. PMID- 1424566 TI - Differential expression of the platelet-derived growth factor-A and -B genes during maturation of monocytes to macrophages. AB - 1. Regulation of platelet-derived growth factor (PDGF)-A and -B gene expression was studied using resting monocytes, in vitro matured monocytes and alveolar macrophages. 2. Resting monocytes constitutively transcribed both PDGF-A and -B genes. When monocytes matured to macrophages in vitro, the transcription rates of both genes increased markedly. 3. Consistent with the transcription rates, resting monocytes constitutively expressed both PDGF-A and -B mRNAs. Interestingly, the PDGF-B mRNA levels increased markedly after the maturation, whereas the PDGF-A mRNA did not change. 4. Alveolar macrophages constitutively transcribed both PDGF-A and -B genes at almost the same rates. However, these cells contained 5-fold more PDGF-B mRNA than PDGF-A mRNA. 5. Immunohistochemical study using anti-PDGF-AA and anti-PDGF-BB antibodies suggested that PDGF-BB homodimers were more abundant than -AA homodimers or -AB heterodimers in alveolar macrophages and in vitro matured monocytes. 6. Together these observations indicate that in vitro matured monocytes and alveolar macrophages preferentially express PDGF-B mRNA and produce PDGF-BB homodimers, despite the equal transcription rates for both PDGF-A and -B genes. PMID- 1424567 TI - Arginase distribution in tissues of domestic animals. AB - 1. A new colorimetric method was used for determination of arginase in different tissues of some domestic animals. 2. In all species studied liver was the richest source of arginase. 3. Significant differences were observed in the specific activity of arginase in livers from different species. 4. In all species, besides liver, kidney and brain also contained significant levels of arginase. 5. In the dog, in addition to the three organs mentioned above, lung, heart, spleen and skeletal muscle showed some arginase activity. 6. In sheep and cattle significant arginase activity was observed in the rumen. No differences were observed between epithelial and muscular layers of different parts of digestive system in all species studied. 7. These results are discussed in terms of the possible role of arginase in different tissues of animals. PMID- 1424568 TI - Comparison of sex steroid hormone-dependent induction of chick oviduct delta aminolaevulinic acid dehydratase during primary and secondary stimulation. AB - 1. A comparative study on primary and secondary stimulation of oviduct delta aminolaevulinic acid dehydratase (ALAD) (EC 4.2.1.24) was carried out with oestradiol-17 beta and/or testosterone administration in immature female chickens during 15-day-primary stimulation, 20-day-withdrawal and 15-day-secondary stimulation periods. 2. Compared with primary stimulation in oestrogenized birds, synthesis and degradation rates of oviduct ALAD molecule during secondary stimulation increased 3.4- and 1.8-fold respectively, resulting in a rapid induction of the enzyme. 3. Specific activity of oviduct ALAD in oestradiol-plus testosterone treated birds became significantly higher than that of oestradiol alone during secondary stimulation, whereas no significant changes were observed during primary stimulation. PMID- 1424569 TI - Effect of adenine metabolites on survival of Drosophila melanogaster of low xanthine dehydrogenase activity. AB - 1. Low xanthine dehydrogenase (LXD) mutant Drosophila melanogaster were fed 0.2% adenine for 7 generations, no adenine for the next 2 generations (relaxed) and 0.2% adenine again for the next 3 generations (rechallenged) to obtain adenine resistant lines of Drosophila (LXD-adenine). Flies grown without adenine served as LXD-controls. 2. Purines ranked as follows; adenine > adenosine > AMP > inosine > IMP in decreasing order of toxicity to LXD-adenine flies. 3. Addition of ribose to 9N position, or phosphate or carboxy to 6C position of the purine ring alleviated the toxicity. 4. More LXD-adenine offspring survived than did LXD control offspring rechallenged with adenine. PMID- 1424570 TI - Postnatal development of hepatic xanthine oxidase in baby pigs and turnover of purine catabolites at reduced ambient temperature. AB - 1. The activity of xanthine oxidase in liver samples of baby pigs up to 4 weeks of age was investigated. On the 3rd day of life the turnover of hypoxanthine and of uric acid were measured after intravenous injection of 3H- and 14C-labelled tracers into animals kept at normal (32 degrees C) and reduced (20 degrees C) ambient temperature. 2. Hepatic xanthine oxidase activity increased progressively from 2 to 28 days of age (r = 0.689; P < 0.001). The increase of Vmax and of KM within 3-4 weeks was about 4.5-fold. 3. In 3-day-old baby pigs kept at normal temperature, pool size and turnover was about 10-fold higher for hypoxanthine than for uric acid. 4. At reduced ambient temperature, the pool size of uric acid increased 3.9-fold (P < 0.01) and turnover 1.6-fold (P < 0.05). For hypoxanthine the increases were insignificant. PMID- 1424571 TI - Effects of a new calf thymus protein on 3-hydroxy-3-methylglutaryl-CoA reductase activity in rat (Rattus bubalus) hepatocyte cells (BRL-3A). AB - 1. In a previous paper we described the purification steps of a new calf thymus protein able to activate the LDL receptor catabolism. 2. In this paper we examine the modulatory effect of this new calf thymus protein on 3HMG-CoA reductase activity in rat hepatocyte cells to better clarify the role of this protein on cholesterol metabolism. 3. The results obtained show that the calf thymus protein inhibits the HMG-CoA reductase, and support the hypothesis that the activation of LDL receptor catabolism is mediated by a decreased amount of cellular cholesterol following HMG-CoA reductase inhibition. PMID- 1424572 TI - Evidence for melanogenesis in the retinal pigment epithelium of adult cattle and golden hamster. AB - 1. The ultrastructure of the retinal pigment epithelium (RPE) of adult Syrian golden hamsters and cattle was examined with respect to pigment granules and phagosomes involved in degradation of disk membranes from rod outer segments. 2. In the RPE of cattle, phagosomes were found that contained an electron-dense melanin-like material that was not autofluorescent and therefore not lipofuscin. 3. Disk membranes of rods are about 4 nm thick and become enlarged (7-20 nm) and electron-dense during degradation in the RPE. 4. Additionally electron-dense vesiculo-globular bodies (10-100 nm) were found in phagosomes during disk membrane degradation and in mature melanin granules. 5. In the RPE of adult hamsters that had been exposed to intense light, premelanosomes containing unmelanised filaments with a striated periodicity were found in the cytoplasm or in association with mature melanin granules. Early and late stage melanosomes were also present. Phagosomes in the RPE contained degraded disk membranes, melanin-like material and melanofilaments. 6. Dopa oxidase was detected ultrastructurally within shed disk membranes that were in close contact with the microvilli of the RPE. 7. The possibility of melanogenesis within phagosomes during disk membrane degradation is discussed. PMID- 1424573 TI - Physical studies of the hemocyanin of the marine gastropod, Kelletia kelleti (Forbes). AB - 1. The hemocyanin of the Californian whelk, Kelletia kelleti, investigated at pH and ionic conditions close to physiological, has a molecular weight close to 9.0 x 10(6) and a sedimentation constant of 114S, characteristic of the di-decameric structure of molluscan hemocyanins. Light-scattering measurements at pH 8.0, 0.05 M Mg2+, 0.01 M Ca2+ gave a molecular weight of 9.0 +/- 0.6 x 10(6), and scanning transmission electron microscopy produced nearly the same particle mass of 9.22 +/- 0.50 x 10(6) daltons (Da). 2. Light-scattering measurements on the fully dissociated monomers in the presence of 8.0 M urea and at pHs 10.6 and 11.0 gave molecular weights of 4.50 x 10(5)-4.91 x 10(5), that are close to one-twentieth of the mass of the parent di-decameric hemocyanin assembly. 3. Changes in pH produced a bell-shaped molecular weight profile, with molecular weights close to 9.0 x 10(6) in the pH region of about 5.5-8.0, and progressive dissociation to 4.5 x 10(5) Da monomers in the region below pH 4.0 and above pH 9.0 or 10, depending on the absence or presence of stabilizing Mg2+ ions (0.01 M). 4. In the absence of divalent ions some aggregation of hemocyanin was found at pHs close to 5.0, with observed molecular weights above 10 x 10(6) (investigated at a hemocyanin concentration of 0.10 g/l). The early studies of Condie and Langer (Science 144, 1138-1140, 1964) had shown that Kelletia kelleti hemocynanin aggregates at acidic pHs close to the isoelectric point, forming linear polymers of the hemocyanin di-decamers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424574 TI - Seasonal changes in the activity of rhodanese in frog (Rana temporaria) liver. AB - 1. The investigators studied annual changes in rhodanese activity in mitochondria and cytosol of frog liver cells (Rana temporaria) and found that the value of the enzyme-specific activity was higher in mitochondria than in cytosol, showing significant seasonal fluctuations. 2. The character of changes in the rhodanese activity in mitochondria, regardless of the sex of the studied animal, was demonstrated to be dependent upon the seasonal changes in frog thyroid gland function. 3. In the supernatant fraction of R. temporaria liver homogenate, seasonal changes of rhodanese specific activity seemed to be related to changes in hepatic function. PMID- 1424575 TI - Preparation of unsaturated disaccharides by eliminative cleavage of heparin and heparan sulfate with heparitinases. AB - 1. Six kinds of unsaturated disaccharides were prepared by enzymatic digestion of heparin and heparan sulfate with heparitinases I0 and IV, and subsequent column chromatography. They were identified by HPLC showing good separation from each other. 2. The content of each unsaturated disaccharide fraction was determined colorimetrically, and found to range from 130.7 to 722.3 mumol. 3. Molecular extinction coefficient of each unsaturated disaccharide was calculated from absorbance at a wavelength of around 230 nm where a peak appeared on the ultraviolet spectrum of each disaccharide solution at pH 2. The values varied from 6000 to 6600. PMID- 1424576 TI - A network thermodynamic model of the concentrating properties of the rabbit/rat kidney in the steady state using the electronic network simulation program SPICE. AB - A model for the simulation of the diluting and concentrating properties of the rabbit and rat kidney is developed. Translation of the physical model into an electronic one brings the model into a form that can be handled by the electronic network simulation program SPICE. The steady state responses of both kidneys to various inputs are calculated under certain conditions. PMID- 1424578 TI - Real-time abdominal fetal ECG recording using a hardware correlator. AB - A real-time fetal ECG monitoring system using abdominal recording is presented. The system is based on an IBM AT compatible personal computer. The computer lacks the performance required for real-time analysis. Therefore, a new design of a fast hardware correlator board was developed to enhance the computer throughput. The technique is based on a cross-correlation procedure. An averaged maternal ECG waveform is derived using the cross-correlation function for the waveform's alignment. With this procedure a template signal corresponding to one complete maternal ECG is obtained. The averaged maternal ECG is then subtracted from the abdominal signals. Thus, it is possible to detect all the fetal ORS complexes in spite of their coincidence with the maternal ECG. An average fetal ECG is then extracted to improve the signal-to-noise ratio, making it possible to recognize fetal P and T waves. PMID- 1424577 TI - A computer model for the study of electrical current flow in the human thorax. AB - Electrocardiography has played an important role in the detection and characterization of heart function, both in normal and abnormal states. In this paper we present an inhomogeneous, anisotropic computer model of the human thorax for use in electrocardiography with emphasis on the calculation of transthoracic potential and current distributions. Knowledge of the current pathways in the thorax has many applications in electrocardiography and has direct utility in studies pertaining to cardiac defibrillation, forward and inverse problems, impedance tomography, and electrode placement in electrocardiography. PMID- 1424579 TI - Treatment time for Amersham caesium-137 manual afterloading system. AB - Currently, the Amersham caesium-137 afterloading system is widely used for gynecological treatment of tumors in uterine cervix. This paper introduces an expert system to determine the time of exposure of an Amersham afterloading system based on different combinations of applicator sources. The efficiency of the expert system achieves 93% of the clinical decisions taken by physicians. It is evaluated by both the experimental results and the actual clinical decisions. PMID- 1424580 TI - Simple SAS macros for the calculation of exact binomial and Poisson confidence limits. AB - Statistical analysis using confidence intervals is now a preferred approach in the medical literature, and confidence limits for binomial proportions and Poisson counts are commonly required. Normal approximations of varying accuracy are often used in such situations and it is not generally realised that non iterative exact solutions are available. This paper shows that the exact binomial and Poisson confidence limits can be expressed very simply in terms of the inverse beta and inverse gamma distributions, and describes two macros in the SAS programming language to perform the computations. The exact solutions are compared with some approximations and further applications of the techniques are described. PMID- 1424581 TI - Reuleaux triangle somatocharts. AB - The three-numeral somatotype index to quantitatively represent human body type has gained general acceptance since being proposed in 1940. The two-dimensional Reuleaux triangle somatochart has been a customary format for graphically representing three-dimensional somatotype data. This paper presents the traditional, quick plot somatochart, the rationale for development of the Health Carter 1980 somatochart with scaled axes and, based on that rationale, a proposal for a somatochart utilizing a traditional x, y-coordinate axis system. Two completed somatocharts are presented; one showing mean somatotypes of collegiate rugby, football and soccer players, and another depicting phenotypic changes in somatotype after diet and exercise. PMID- 1424582 TI - Evaluating agreement between two methods for measuring the same quantity: a response. AB - A method comparison study is typically concerned with evaluating the agreement between a "new" method against an "established" method for measuring the same quantity. Various statistical indices have been advocated for measuring the extent to which two methods give identical readings, that is, absolute method agreement. This article scrutinizes two contending statistical indices, the intraclass correlation and the "limits of agreement", for measuring absolute method agreement, and found neither index to be without deficiency. Notwithstanding, each index can serve a useful role in quantitating method agreement in carefully considered situations. PMID- 1424583 TI - An on-line data acquisition microcomputer: system for monitoring physiological variables during rest and exercise. PMID- 1424584 TI - Clinical, immunological and bacteriological evaluation of adverse reactions to skin-penetrating titanium implants in the head and neck region. AB - Between 1977 and October 1989, 445 patients have been treated with bone-anchored skin-penetrating titanium implants for anchorage of facial prostheses or bone conducting hearing aids, at the Ear, Nose and Throat Department at Sahlgren's Hospital in Gothenburg. The majority of patients had no adverse skin reactions, while a few patients were responsible for the majority of the adverse reactions. The aim of our study was to analyse differences between these groups. We started a clinical study on 9 patients with a clinical history of adverse skin reactions around the titanium implants and 9 patients without adverse skin reactions were used as controls. None of the patients had delayed hypersensitivity to titanium. Microbiological analyses showed that when there was clinical irritation, Staphylococcus aureus could be isolated. PMID- 1424585 TI - Contact dermatitis from telefax paper. AB - A nonatopic female secretary developed hand dermatitis after 1 year of full-time work with telefax paper. Her dermatitis improved on sick leave and vacation and relapsed at work. Patch testing showed allergic reactions to several fragrances, balsam of Peru, colophony and neomycin. In 3 patch test sessions, her own telefax papers gave a doubtful reaction which persisted for 4 days, but it could not be determined whether the reactions were allergic or irritant. The colophony content of the telefax paper was about 1%, and it was possible that colophony in the telefax paper was responsible for the weak path test reactions. Accordingly, the contact dermatitis would have been allergic. The patient has now been relocated, does not handle telefax paper, and is symptomless. We concluded that our patient had an occupational hand contact dermatitis induced by telefax paper and possibly caused by colophony allergy. PMID- 1424586 TI - Study of dose-response relationship in contact sensitivity using an in vitro assay. AB - Dose-response relationships in contact sensitivity were evaluated in guinea pigs using an in vitro assay. Guinea pigs were sensitized with different doses of 1 chloro-2,4-dinitrobenzene (DNCB) and challenged with DNCB and 2,4-dinitrobenzene sulfonic salt (DNBS). Lymph node cells from sensitized and control guinea pigs were cultured in the presence of different doses of DNCB and DNBS at 8 x 10(5) cells/well, respectively. The sensitivity was evaluated by the lymphocyte transformation test (LTT), which was assessed by uptake of 3H-thymidine. The results indicated that there were significant correlations between the doses of sensitizers and the values of LTT in both phases of induction and challenge. Thus, the presence of higher numbers of LTT-reactive lymphocytes in the circulation may well correlate with the sensitizing doses. The values examined by in vitro assay correlated well with patch test readings (r = 0.653), indicating that following the increment of degree of patch test reactions, the values of SI were also increased. The in vitro LTT may discriminate between positive patch test reactions and negative or doubtful reactions, but not between weak positive and strong positive reactions. The in vitro assay reproduced the cross-reaction between DNCB and DNBS which was confirmed in vivo. PMID- 1424587 TI - Sensitization to azo dyes: negative patch tests to yellow and red azo dyes in printed paper. AB - An over 2 x fold increase in para-aminoazobenzene allergy was observed in patients with allergic contact dermatitis during the years 1990-1991. Presuming that an increase in colour-printed newspapers might be a new unrecognized source of clinical allergy to azo dyes, patch tests were performed in 32 patients with an established p-aminoazobenzene allergy using a series of important azo dyes used in offset printing ink (Pigment Yellow 12, Pigment Yellow 13, Pigment Red 53, Pigment Red 57), as well as with dye-containing inks and specimens of colour printed newspaper containing these azo dyes. In 25 out of the 32 patients (78%), positive patch tests were seen to textile azo dyes, in particular to Disperse Orange 3 (24 patients). In none of the 32 patients were reactions observed to the azo dyes used in printing ink, to the inks used or to the colour-printed paper specimens, indicating that these products were apparently not a cause of contact dermatitis in our group of patients with azo dye sensitization. PMID- 1424589 TI - Electrical impedance applied to non-invasive detection of irritation in skin. AB - Healthy volunteers were subjected to irritation by sodium lauryl sulphate at concentrations in the range 0.002% to 5.0% applied in Finn Chambers for 24 h. Test sites were visually assessed 1 h and 24 h after cessation of exposure. At the same times electrical impedance was measured with a new impedance device which allows non-invasive local measurements to a controlled depth. Close agreement between concentration and an irritation index calculated from electrical impedance parameters was found over the whole concentration range for most test persons. At concentrations below 0.2%, visual scores were zero. These results suggest that electrical impedance can be used as an objective tool to record irritation, and further that electrical impedance might be a more sensitive method than the commonly used visual readings. PMID- 1424588 TI - Allergic contact dermatitis from formaldehyde. A case study focussing on sources of formaldehyde exposure. AB - Formaldehyde is a common contact allergen. The prognosis of formaldehyde sensitive patients is generally considered to be bad because of widespread exposure to formaldehyde. 11 patients with eczema and a positive patch test to formaldehyde were interviewed by a dermatologist and a toxicologist/chemist and instructed to fill in a questionnaire on exposure to chemical products. The content of formaldehyde and formaldehyde releasers in such products was examined using the database of the Danish Product Register (PROBAS) and by supplemental inquiries of manufacturers or importers. All the patients used one or more products containing formaldehyde or formaldehyde releasers. Sources of exposure were cosmetics and personal care products, dishwashing liquids, water-based paints, photographic products, etc. Patients were advised to use alternatives to those products containing formaldehyde or formaldehyde releasers. The status of 10 out of the 11 patients' eczema at follow-up was about 1/3 healed, 1/3 improved and in 1/3 no change. When the relevance of positive patch test reactions to formaldehyde was based on information obtained on exposure, a very high rate of current relevance was found. Computerized data on product composition allows the screening of products for contact allergens and also generates lists of contact allergens indicated for patch testing, based on the patients' own products. PMID- 1424590 TI - Contact sensitivity to flavourings and perfumes in atopic dermatitis. AB - 16 children with atopic dermatitis and 4 nonatopics were skin tested with flavourings and perfumes. Immediate reactions to balsam of Peru and fragrance-mix were found in 9 atopics, and none among nonatopics. An irritant is more probable than an immunologic mechanism. Allergen solutions should probably be assayed at a lower concentration in atopic patients. This study points to a possible aggravating factor from perfumes and flavourings ingested, inhaled, or used as cosmetics. PMID- 1424591 TI - Oscar Wilde's skin disease: allergic contact dermatitis? AB - During the last years of his life, Oscar Wilde (1856-1900) suffered from a suppurating otitis media as well as from an unidentified skin disease. The eruption was localized to his face, arms, chest and back and itched severely. A new theory is suggested, based on the fact that Wilde almost certainly used a dye to conceal his rapidly graying hair. He sensitized himself to p-phenylenediamine and developed a stubborn allergic contact dermatitis. Patch testing, the only proof of such a diagnosis, had not yet been devised. PMID- 1424592 TI - Photocontact dermatitis from ketoprofen with cross-reactivity to ibuproxam. PMID- 1424593 TI - Allergic contact dermatitis from coal tar. PMID- 1424594 TI - Contact sensitization due to isophoronediamine. PMID- 1424595 TI - Allergic contact dermatitis due to phenol-formaldehyde resins in a knee-guard. PMID- 1424596 TI - A survey of skin problems in day-care workers. PMID- 1424597 TI - Occupational dermatitis in a ewe milker. PMID- 1424598 TI - Contact allergy to budesonide in a nasal spray. PMID- 1424599 TI - Systemic contact allergy from occupational contact with ethyl ethoxymethylene cyanoacetate. PMID- 1424600 TI - Contact dermatitis from crotamiton. PMID- 1424601 TI - Studies of the quenching phenomenon. PMID- 1424602 TI - Erythema induced by organic solvents: in vivo evaluation of oxygenized and deoxygenized haemoglobin by reflectance spectroscopy. AB - OBJECTIVE: (i) using a new non-invasive technique capable of evaluating quantitatively and qualitatively the haemoglobin content of the skin (ii) to evaluate delipidization induced by organic solvents. PATIENTS: 11 Caucasians treated for 1 min in a randomized manner on the volar forearm with a mixture of chloroform/methanol (2:1) (CM) and ether/acetone (1:1) (EA) to delipidize the skin. METHOD: erythema was evaluated by computerized remittance spectroscopy immediately after delipidization and hourly for 2 h. RESULTS: only CM application induced subjectively observed and objectively quantified erythema. Erythema was related to a significant increase in oxygenized haemoglobin content due to dilatation of arterioles in the subpapillary plexus (P less than 0.01). The increased blood flow induced a significant (P less than 0.01) reduction in de oxygenized haemoglobin in venous vessels immediately after CM application. CONCLUSION: short contact with certain potent solvent mixtures causes erythema, possibly due to massive lipid extraction and damage of the skin barrier. Using computerized remittance spectroscopy the visible erythema was composed of an increase in oxygenized haemoglobin and a relative decrease in deoxygenized haemoglobin. PMID- 1424603 TI - Clinical manifestations and antibiotic treatment of Lyme disease. AB - As the incidence of Lyme disease increases in Connecticut and world-wide, considerable attention has been given to its prompt diagnosis and treatment. Creating further interest in this infection is the awareness that inappropriate therapy may result in significant disabling sequelae many years later. In this review, we focus mainly on current treatment options, but stress that the recommendations may change appreciably, as more information appears on the efficacy of new antibiotics. PMID- 1424604 TI - Pulmonary carcinosarcoma: report of a case with unusual histologic features. AB - An unusual case of a 56-year-old male with carcinosarcoma of the lung containing three malignant mesenchymal elements is reported. The clinical, radiographic, gross, and immunohistochemical findings are presented. The theories addressing the histogenesis of carcinosarcoma are discussed with special emphasis on the findings in this case. PMID- 1424606 TI - A country doctor in Connecticut medicine and politics: William L. Higgins. 1867 1951. PMID- 1424605 TI - Repeat coronary artery bypass: a seven-year experience. AB - Repeat coronary artery bypass (RCAB) procedures were performed on 323 patients from March 1984 through December 1990. The mean interval between bypass operations was 7.8 years. The operative mortality rate was 4.6%; six of the 15 deaths (40%) occurred in the operating room. Fourteen of the 15 operative deaths (93.3%) were cardiac, all but one of which were due to ventricular failure. Follow-up data for 83 of 91 (91.2%) patients at least five years following RCAB show that 64 (77.1%) are still alive, 39 (60.9%) of whom remain free of cardiac symptoms. Findings in this report, which are notably consistent with those of previous reports, are a significantly higher operative mortality rate and higher risk of death in the operating room in patients undergoing repeat bypass compared with those having initial coronary artery bypass. The challenge of reducing the mortality risk following coronary reoperation is discussed in this report. PMID- 1424607 TI - The realities of health care reform. PMID- 1424608 TI - Confidentiality and the HIV-positive patient. PMID- 1424609 TI - Financial aspects of the provision of care to AIDS patients at Hartford Hospital. AB - Data on the provision of care to persons with AIDS at Hartford Hospital are presented for the years 1988 and 1989. Approximately 2% of the total operating loss from uncompensated care at the hospital was due to patients with AIDS during both of those years. While the hospital continues to show a net surplus of revenues over expenses, the operating loss incurred by the hospital for the provision of care to hospitalized case-definition AIDS patients increased by 88.1% between 1988 and 1989. PMID- 1424610 TI - Hageman factor deficiency presentation and implications for management. AB - One of the more fascinating aspects of patient management arises when dealing with coagulation disorders. Factor XII deficiency, first described by Ratnoff in 1968, is one such coagulation disorder which provides some interesting challenges in management. Factor XII deficiency has been shown to be an inherited autosomal recessive disorder. The presence of Hageman factor abnormality trait can be clinically suspected in a patient with a prolonged activated partial thromboplastin time (APTT), normal prothrombin time (PT), normal bleeding time, and no clinical history of bleeding. Once suspected, the deficiency can be confirmed by normalization of partial thromboplastin time (PTT) with normal aged plasma and by factor assay. The importance of understanding the mechanism of factor XII deficiency has clinical significance when attempts are made to heparinize individuals who have this deficiency. Three methods can be used to monitor therapy: the chromogenic heparin assay, the citrated thrombin time, and the recalcified thrombin time. Two cases are presented. PMID- 1424611 TI - Risk management alert: a summary of perinatal cases. AB - Connecticut Medical Insurance Company (CMIC) cases related to obstetrical care and the newborn represent the single most costly exposure to the Company. CMIC undertook the review of its perinatal cases, open and closed, to identify common elements that increased the liability exposure of individual physicians as well as the overall exposure to the Company. PMID- 1424612 TI - Euthanasia, mercy-killing, or killing? PMID- 1424613 TI - Psychiatry as a basic medical science. 1942. PMID- 1424614 TI - De senectute: who's in charge here? PMID- 1424615 TI - Abortion 1992: the boundaries of regulation. PMID- 1424616 TI - A system to honor individualism? PMID- 1424617 TI - Cumulative stress death. PMID- 1424618 TI - A randomized clinical trial of mifepristone (RU486) for induction of delayed menses: efficacy and acceptability. AB - Mifepristone (RU486) should be useful for inducing menstrual bleeding in women with menses delayed up to 10 days. We evaluated this potential use for "menstrual regulation" in a randomized clinical trial with 16 women, half of whom received a single 600 mg dose and half of whom received a placebo. Four of eight women in each treatment group proved to be pregnant. Seven of eight who received mifepristone were not pregnant at two-week follow-up, in contrast to four of eight who received the placebo (p = 0.15). Mifepristone may hold promise for "menstrual regulation" for women who do not have access to medical confirmation of pregnancy or who choose not to have this determination made. PMID- 1424619 TI - A study of gemeprost alone, dilapan or mifepristone in combination with gemeprost for the termination of second trimester pregnancy. AB - It is well established that abortion can be induced successfully in midtrimester of pregnancy by gemeprost vaginal pessaries. A randomised study was carried out to determine the efficacy of mifepristone and dilapan in combination with gemeprost for second trimester termination between 12-18 weeks' gestation. A contemporary group of women treated with gemeprost alone was used as a control group. A single course of 4 x 1 mg gemeprost pessaries was administered every six hours. If abortion had not occurred after 24 hours, a further course of 5 x 1 mg pessaries was administered every three hours over the next 24 hours. In the first twenty hours after administration of gemeprost, 95%, 85% and 72% of women aborted in the mifepristone, dilapan and the control group, respectively. The median induction-abortion interval in the mifepristone group (6.6h) was significantly shorter than the other two groups and fewer pessaries were required to induce abortion. The incidence of diarrhoea and vomiting was lower in the mifepristone than the other two study groups. This study demonstrated the efficacy of mifepristone in combination with gemeprost and this regimen is associated with fewer gastrointestinal side effects. PMID- 1424620 TI - Triphasic combination of ethinyl estradiol and gestodene. Long-term clinical trial. AB - A triphasic oral contraceptive containing ethinyl estradiol and gestodene was used by 1933 women for up to 36 cycles in order to evaluate contraceptive efficacy, general tolerance and cycle control. Altogether, 30,763 treatment cycles were recorded. Two pregnancies were seen, both of them classified as user failure. The rates of spotting and breakthrough bleeding fell below the rates of the pre-treatment cycle after the first three months of treatment. Adverse events were mostly minor with breast tension and headaches the most common complaints. After the first three cycles, the incidence of most complaints was the same as or even lower than in the pre-treatment cycle. Blood pressure and body weight remained practically unchanged. The trial preparation provided reliable contraception with good general tolerance and cycle control when taken for up to three years. PMID- 1424621 TI - Pharmacokinetics of gestodene in 12 women who received a single oral dose of 0.075 mg gestodene and, after a wash-out phase, the same dose during one treatment cycle. AB - The pharmacokinetics of gestodene (GEST) was determined in 12 healthy women (age 22 to 34 years), following single dose administration of 0.075 mg GEST. The same preparation was also administered during one treatment cycle after a wash-out phase of 1 week. After single dose administration, maximum concentrations of GEST in the serum were 4.9 +/- 2.5 ng/ml. Post maximum drug levels declined biphasically with half-lives of 0.2 +/- 0.2 h and 14.9 +/- 6.7 h, respectively. The apparent clearance was calculated to be 0.8 +/- 0.4 ml x min-1 x kg-1. The free fraction of GEST was 1.3 +/- 0.3% and the fractions bound to SHBG and albumin were 64.3 +/- 10.7% and 34.4 +/- 10.4%, respectively. The results showed that there was a gradual decrease in serum trough levels of GEST during the cycle, due to a concomitant and equally high decrease in SHBG concentrations in the serum of about 26%. At the end of one treatment cycle, the free fraction of GEST increased to 1.8 +/- 0.5%, the SHBG-bound fraction decreased to 57.0 +/- 10.2% and the albumin-bound fraction increased to 41.3 +/- 9.9%. Total serum clearance increased during the same time period from a mean value of 0.8 to about 1.2 ml x min-1 x kg-1. The clearance of unbound GEST, however, remained unchanged. An examination of the free GEST concentrations revealed the same time course of GEST trough levels during the cycle as the simulated curve. This was derived from the pharmacokinetic parameters which were obtained after single dose administration. Thus, the present study showed that the pharmacokinetics of GEST can be fully explained on the basis of single dose pharmacokinetics and the changes in serum protein binding which were caused by a reduction of SHBG levels in the serum during chronic treatment with GEST. There was no evidence of GEST inhibiting its own metabolism. PMID- 1424622 TI - Use of injectable progestin (medroxyprogesterone acetate) in adolescent health care. AB - To assess medroxyprogesterone acetate (DMPA) prescription practices in adolescent health care practices, an anonymous questionnaire was distributed to 160 American and Canadian physicians attending the 1991 meetings of either the Society for Adolescent Medicine or the North American Society for Pediatric and Adolescent Gynecology. Of 54 (33.7%) physicians who responded, 33 (61.1%) reported prior prescription of an injectable progestin (DMPA) as a form of birth control. Of those, 15 (45.5%) had prescribed it to 10 or more adolescents. Twelve (57%) pediatricians but only 3 (25%) gynecologists reported prescribing DMPA to 10 or more adolescents (p = 0.074). Female physicians were more likely to have prescribed DMPA to adolescents than male physicians (p = 0.009). Mental retardation was considered the strongest "potential indication" for DMPA administration by 48 physicians responding to a 5-point Likert scale. The study suggests that physicians with interest or expertise in Adolescent Medicine are using DMPA as a form of birth control for selected young women in spite of the lack of Food and Drug Administration approval. A centralized DMPA registry is suggested to monitor adverse outcomes in users. PMID- 1424623 TI - Long-term use of depot-norethisterone enanthate: effect on blood lipid fractions. AB - This is the third report of a metabolic study on 56 long-term users (24 for 2-5 yr; 32 for over 5 yr) of the injectable contraceptive norethisterone enanthate (Net-En) and deals with the effects on the blood levels of lipoprotein fractions. There was no significant difference between this group and a group of 30 non users in serum concentrations of triglycerides, total cholesterol, low density and very low density lipoproteins. There was a significant reduction in mean high density lipoprotein levels between the controls and the user groups (16% for the intermediate duration and 12% for the longer duration). Age, ethnic group, body mass index and a close family history of cardiovascular disease were taken into account, as were various lifestyle factors: diet, exercise, alcohol consumption and smoking. In a smaller group, levels of apoproteins A and B were also assayed. There was a significant reduction in apoprotein A between controls and all users, but the significance was lost on adjusting for confounding variables. Consideration was given to the ratio of total cholesterol to high density lipoprotein cholesterol as an index of coronary risk. There were no significant differences in the total cholesterol:HDL-C ratio between controls and user groups. There was a significant interaction with ethnic group (Caucasian or Afro Caribbean) in the response to duration of use. PMID- 1424624 TI - Carbohydrate metabolism before and after Norplant removal. AB - Changes in carbohydrate metabolism, measured by oral glucose tolerance test, were studied in Norplant users before and after removal. The mean area under the glucose curve rose from 24.7 min mmol/L before Norplant insertion to 35.1 min mmol/L before removal and decreased to 26.1 min mmol/L four weeks after Norplant removal. The areas before insertion and after removal were not statistically different (95% confidence interval -3.3 to 0.56, P = 0.16). The mean areas under the insulin curves before insertion (53.14 min uU/L) and after removal (59.46 min uU/L), however, were significantly different (95% confidence interval -7.64 to 5.0, P less than 0.0001). We conclude that changes in carbohydrate metabolism induced by Norplant are reversible once the implants are removed. While the changes in glucose induced by Norplant returned to pre-insertion levels within 4 weeks after removal, insulin changes were slower to return to pre-insertion values. PMID- 1424625 TI - Effect of Norplant-2 rods on haemostatic function. AB - A longitudinal study on one-hundred Singaporean women using Norplant-2 rod implant for contraception and their effects on the haemostatic function was carried out. There was a decrease in vitamin K-dependent Factors II, VII and a tendency towards lowered fibrinolytic activity after prolong use of Norplant-2 rods. The results indicate that the Norplant-2 rod implant system does not contribute towards hypercoagulable state but increased platelets and accelerated platelet aggregation observed will require further study to ascertain whether there is a concomitant increase in platelet activation. PMID- 1424626 TI - Influence of different progestogens on blood pressure of non-anaesthetized male spontaneously hypertensive rats. AB - The aim of the study was to find out if synthetic progestins with significant antimineralocorticoid activity would have a beneficial effect on blood pressure. Male spontaneously hypertensive rats were treated daily for four weeks with different progestogens by subcutaneous injection. Arterial pressure of the conscious animals was measured at three-day intervals. Progestogens were dosed on the basis of their progestogenic activity, whereby the dosages corresponded to the 10-fold effective dose for inhibition of ovulation in rats. For comparison, spironolactone as well as progesterone itself were included in the study. After four weeks' treatment, plasma volume, extracellular fluid volume (ECFV) and the sodium and potassium concentrations in the plasma were measured. In control animals, there was a slight decrease in blood pressure over the four-week experimental period. Progesterone and spironolactone similarly influenced blood pressure. A new progestin with significant antialdosterone activity, dihydrospirorenone (code No. ZK 30.595), slightly but significantly decreased the ECFV, plasma sodium concentration and slightly but insignificantly decreased blood pressure as compared to vehicle-treated controls. Synthetic progestins lacking this antimineralocorticoid activity did not decrease blood pressure, but rather induced a slight increase in this animal model. The results clearly support the hypothesis that synthetic progestins, like endogenous progesterone, all of them with inherent antialdosterone activity, decrease the ECFV and so might have an impact on extracellular fluid hemostasis as well as blood pressure regulation. PMID- 1424627 TI - The challenge for equine exercise physiology. PMID- 1424628 TI - The Olafson Medal. William J. Hadlow. PMID- 1424629 TI - The Olafson Medal. Hans-Jorgen Hansen. PMID- 1424630 TI - The Olafson Medal. William J. Hartley. PMID- 1424631 TI - Bacteria and yeast on the surface and within non-inflamed hair follicles of skin biopsies from cats with non-neoplastic dermatoses. AB - Coccoid bacteria and/or yeasts were found in the surface keratin or exudate or, rarely, the pilar canal of non-inflamed hair follicles upon light microscopic examination of skin biopsies from 57 of 338 cats (16.9%) with non-neoplastic skin disorders. The presence of these microorganisms did not appear to suggest a specific dermatosis, nor the existence of a clinically relevant infection in the majority of cases. PMID- 1424632 TI - Bacteria and yeast on the surface and within non-inflamed hair follicles of skin biopsies from dogs with non-neoplastic dermatoses. AB - Coccoid bacteria and/or yeasts were found in the surface keratin or exudate and/or in the pilar canal of non-inflamed hair follicles upon light microscopic examination of skin biopsies from 191 of 3,387 dogs (5.6%) with non-neoplastic skin disorders. The presence of surface cocci and/or yeast did not appear to suggest a specific dermatosis, nor the existence of a clinically relevant infection in the majority of cases. However, follicular cocci and/or yeast almost always indicated the presence of a clinically relevant infection. PMID- 1424633 TI - Microscopic anatomy of the skin of the woodchuck (Marmota monax): comparison of woodchuck hepatitis virus-infected and non-infected animals. AB - Thirty-three woodchucks were used in this study. Seventeen animals were healthy adults, not infected with woodchuck hepatitis virus (WHV); 10 were healthy adults infected with WHV; 4 were noninfected neonates; 2 were infected neonates. Within the 4 groups of woodchucks, no histologic differences were detected on the basis of sex or age. Neither were histologic findings different between infected and noninfected woodchucks of similar ages. The average thickness of skin (as measured from the skin surface to the inner limit of the dermis) from the general haired body area was 2394 microns. The skin was thickest on dorsal body areas, and gradually became thinner on ventral body and medial limb areas. The epidermis consisted of 4 layers: stratum basale, stratum spinosum, stratum granulosum, and stratum corneum. A stratum lucidum was present only in the epidermis of the footpads. There was no clear distinction between the superficial dermis and the deep dermis, except for the subtle differences in arrangement and size of collagen fibers. Elastic fibers were seen throughout the dermis, being more prominent in the superficial portion. Both compound and simple hair follicle arrangements were seen, with compound being more common. The arrectores pilorum muscles were largest in the skin over the dorsal body areas. Sebaceous glands were present either within the outer root sheath of hair follicles or in the dense connective tissue surrounding hair follicles. No apocrine sweat glands were found. However, there were abundant eccrine sweat glands in the subcutaneous fat of the footpads. PMID- 1424634 TI - Skin disorders of the laboratory woodchuck (Marmota monax): a retrospective study of 113 cases (1980-1990). AB - An 11-year retrospective study was conducted on the dermatoses occurring in 113 woodchucks from a colony at the College of Veterinary Medicine at Cornell University. Bacterial dermatitis was the most common dermatologic disorder, accounting for 70.2% of the cases. The highest incidence of bacterial dermatitis occurred in September/October prior to hibernation and in February/March during the breeding season. Other dermatoses observed during the study period included Taenia crassiceps infection, microfilarial dermatitis, telogen defluxion, various neoplastic and hyperplastic lesions, and various neonatal conditions associated with trauma and/or bacterial infection. No association was found between any of these dermatoses and the presence of woodchuck hepatitis virus infection. PMID- 1424635 TI - The use of retrievable electrodes for recording gastric myoelectric activity after spontaneous gastric dilatation volvulus in dogs. AB - Gastric myoelectric activity was measured in 10 dogs with spontaneous gastric dilatation-volvulus (GDV). Myoelectric activity was recorded with temporary, retrievable wire electrodes placed on the serosal surface of the stomach after derotation and tube gastrostomy. Gastric myoelectric activity was recorded for 1 hour daily, beginning with the day of surgery (less than 24 hours), 24, 48, 72, 96, 120, 144, and 168 hours after surgery. Recordings were also obtained for 1 hour daily after feeding, beginning 24 hours after surgery. Bradygastria was the predominate dysrhythmia immediately after surgery and at hour 24. The mean slow wave frequency was more than normal at hours 48 to 168 due to an increase in tachygastria and arrhythmias. The slow wave frequency significantly decreased after feeding at hours 120 and 144. The overall mean percentage of dysrhythmias was significantly decreased after feeding at hour 72 only. The mean percentage of spike activity ranged from 37.7 +/- 12.5 to 75.7 +/- 6.2 throughout the 8-day study period. Thus, gastric myoelectric activity was disrupted in these dogs with spontaneous GDV and subsequent tube gastrostomy. Feeding did not greatly diminish these dysrhythmias. PMID- 1424636 TI - Secretion of tumor necrosis factor by endotoxin-treated equine mammary exudate macrophages: effect of dexamethasone and pentoxifylline. AB - Secretion of tumor necrosis factor (TNF) by equine mammary exudate macrophages (MEM phi) exposed to bacterial lipopolysaccharide (LPS) was dose-dependent and was maximal (216.5 +/- 51.9 U/ml) at 100 micrograms LPS/ml, the highest concentration tested. All concentrations of dexamethasone tested (10(-8) to 10( 4) M) significantly (P less than or equal to 0.05) inhibited TNF production by MEM phi when the agent was added 1 hour before LPS. Pretreatment with pentoxifylline at concentrations greater than 3 micrograms/ml also significantly (P less than or equal to 0.05) reduced secretion of TNF by MEM phi. The inhibitory effect of dexamethasone (10(-4) M) was observed when the agent was added to MEM phi from 30 minutes before until 4 hours after LPS. Pentoxifylline (100 micrograms/ml) significantly (P less than or equal to 0.05) suppressed TNF when added from 2 hours before until 2 hours after LPS; however, when pentoxifylline addition was delayed until 8 hours post-LPS, TNF production was enhanced. These apparent inhibitory effects of dexamethasone and pentoxifylline were not due to reduced macrophage viability or to interfering effects of the agents at the level of the TNF bioassay. PMID- 1424637 TI - Primary pulmonary chondrosarcoma in a dog. AB - Extraosseous chondrosarcomas are uncommon in the dog, and those originating in the lung are rare. This report presents a 9-year-old Beagle dog with a pulmonary mass which caused depression, fever, tachypnea, cough, and laboratory abnormalities. The mass was composed predominantly of chondroid tissue, and was histologically diagnosed as chondrosarcoma. PMID- 1424638 TI - Daily variability of equine fecal strongyle egg counts. AB - Fecal egg counts often are used for diagnosing equine strongyle infections and estimating the number of eggs shed in the feces. An individual egg count should be interpreted in view of the normal fluctuation of egg numbers in an individual horse. In this study, the daily variability of strongyle fecal egg counts from horses was investigated. The Cornell-McMaster egg-counting technique was used to estimate the eggs per gram of feces in repeated daily fecal samples from 39 horses. The variation of the daily egg counts across 4 days was greater than would be expected if a consistent number of eggs were produced and dispersed randomly in the feces. The means and variances of the daily counts from each horse had a logarithmic relationship. For practical purposes, however, the fluctuation of egg counts is low enough for the fecal egg count to be used to identify horses for treatment, to estimate pasture contamination, or to assess response to therapy. PMID- 1424639 TI - Preoperative and postoperative hemostatic profiles of dogs undergoing ovariohysterectomy. AB - Hemostatic profiles were evaluated in 15 healthy dogs immediately before and 24 hours after celiotomy for routine ovariohysterectomy. Prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation products, antithrombin III activity, platelet count, and hemogram were measured. There were no significant changes in prothrombin time, activated partial thromboplastin time, fibrin degradation products, antithrombin III activity, or platelet count. Fibrinogen concentration was significantly higher following surgery. Postoperative leukocyte differential counts were typical of stress leukograms, and were characterized by leukocytosis, neutrophilia, lymphopenia and eosinopenia. Mild decreases in packed cell volume, red blood cell count and hemoglobin concentration were consistent with minor blood loss during surgery or fluid retention and hemodilution postoperatively. It was concluded that celiotomy and routine ovariohysterectomy in healthy dogs did not alter hemostatic profiles 24 hours after surgery. Abnormal postoperative hemostatic profiles should not be attributed to surgery alone; other causes of abnormal hemostatic profiles should be investigated. PMID- 1424640 TI - Metabolic fate of FCE 22716, a new antihypertensive agent, and of its N-oxide (FCE 24220) in the rat. AB - [3H]-FCE 22716 and [3H]-FCE 24220 were given both orally and intravenously to the rat. Radioactivity was mainly eliminated by the faecal route after oral administration in both cases. After intravenous administration, renal excretion was twice the faecal one in the case of FCE 22716, whereas for FCE 24220 the two routes were equal. In urine FCE 22716 was eliminated almost completely unchanged after both oral and intravenous administration. FCE 24220 was extensively reduced to FCE 22716 after oral administration, whereas after intravenous treatment, this reduction, although important, was not complete. PMID- 1424641 TI - Excretion balance and urinary metabolic pattern of [3H]cabergoline in man. AB - After oral administration of [3H]cabergoline to man at a single nominal dose of 0.6 mg/subject radioactivity is mainly eliminated by the faecal route (72% of the dose after 10 days). Urine contains 18% of the dose after the same period. The unchanged drug and metabolites present in urine were identified by comparison with reference compounds and quantified by radio-TLC analysis. Cabergoline is extensively metabolized. Unchanged drug in 0-24 h urine represents less than 14% of urinary radioactivity, reaching 20% in 0-96 h urine. The acid derivative FCE 21589 is the main metabolite, amounting to 38% and 30% of the urinary radioactivity in 0-24 h and 0-96 h urine, respectively. The amide derivative FCE 21590 appears to be present in only a small amount, accounting for no more than 4% of the urinary radioactivity in the urine of the first 24 hours after administration and increasing to about 8% in the 0-96 h urine. PMID- 1424642 TI - The effect of antacid on aspirin pharmacokinetics in healthy Thai volunteers. AB - The effect of antacid on aspirin pharmacokinetics and bioavailability was determined in 10 healthy adult male and female volunteers, aged 20-45 years old. Each subject received 650 mg of aspirin orally after an overnight fast. The wash out period was 14 days and then all subjects were given 650 mg of aspirin 10 minutes after antacid (aluminium hydroxide and magnesium hydroxide). Plasma aspirin, salicylate and salicyluric acid levels were determined by a specific high performance liquid chromatographic analysis. Individual plasma profiles were analysed using compartmental and non-compartmental methods. The results show that antacid affected the relative bioavailability of aspirin since the mean peak concentration (Cmax) of aspirin was significantly higher when antacid was given. However, the time to reach peak concentration (Tmax) and the area under the plasma concentration-time curve (AUC) showed no significant difference between the two treatments. It was, therefore, not possible to conclude that the non bioequivalence was caused by a difference in rate or amount of aspirin absorption, or both. No significant difference was observed in Cmax, Tmax, AUC, t1/2, Ka, Kel of salicylate and salicyluric acid. However, the rate of total salicylate absorption was increased since the absorption rate constant (Ka) was higher when antacid was given. This may provide a more rapid effect of the drug. PMID- 1424643 TI - A comparison of metronidazole distribution following intravenous metronidazole and metronidazole phosphate disodium in mice. AB - The distribution of metronidazole following intravenous metronidazole (MTZ) and metronidazole phosphate disodium (MNP) in mice was investigated by HPLC. The results showed no significant differences in the metronidazole concentrations of liver, kidney, heart, spleen, fat, brain, lung, stomach, jejunum, skeletal muscle, ovary, testis and epididymis (P greater than 0.05). It can be concluded that using MNP as a water-soluble substitute for MTZ should not influence the distribution of metronidazole in mice. PMID- 1424644 TI - Biochemical basis of cytotoxic activity of some new N'-oxides of N',N' dimethylaminoalkylamides of dodecanoic acid. AB - The objective of the present investigation was to screen a series of new N' oxides of N',N'-dimethylaminoalkylamides of dodecanoic acid for activity in vitro and to investigate the biochemical mode of action. On the basis of primary screening, one of the most active compounds, namely the N'-oxide of 10-(N',N' dimethylaminodecyl)amide of dodecanoic acid (n = 10) was chosen for detailed biochemical study. This compound inhibited the incorporation of 14C-precursors (adenine, valine, thymidine, uridine) into appropriate macromolecules of P388 murine leukemia and Ehrlich ascites carcinoma cells. The amine oxide also interfered with energy-yielding processes (aerobic glycolysis, endogenous respiration). Cytotoxicity is a consequence of the cytolytic activity of the compounds mentioned above. Membranous effects were demonstrated by the measuring of the release of cytoplasmic materials absorbing at 260 and 280 nm, marker enzyme activities (LDH, MDH), release of protein from the cells into the culture medium, as well as by morphological examination. It is evident that the site of action of the amine oxides investigated was the biological membrane which, after interaction with the amine oxides, showed changes in molecular organization and osmotic and permeability characteristics. PMID- 1424645 TI - Accuracy of intraocular pressure measurements with two different tonometers through bandage contact lenses. AB - The intraocular pressure (IOP) of nine cadaver eyes was set by a manometer at 10 mm Hg increments from 10 to 50 mm Hg. Pressure measurements at each of these settings were taken using the Digilab Pneumatonometer and Tono-Pen to determine the accuracy of these instruments. In addition, four brands of therapeutic contact lenses were placed on the eyes, and IOPs were measured through them to determine whether or not comparable IOPs could be obtained through a range of bandage contact lenses. We found a significant difference (p < or = 0.0000) between the measurements obtained by the two instruments at a given manometric setting. Digilab Pneumatonometer's pressures correlated well with manometric pressures. Tono-Pen consistently underestimated manometric pressures. At 50 mm Hg, Digilab Pneumatonometer's mean measurement was 47.5 mm Hg, whereas Tono-Pen's mean was only 38.9 mm Hg. IOPs assessed through all contact lenses were comparable to the measurements without lenses. Multiple regression of score showed that the measured pressure was explained by manometric pressure (81%), the choice of instrument used (5.5%), and the lens thickness (0.09%). The Pierson correlation coefficient was 0.93. This study showed that Pneumatonometer could accurately measure IOP with and without a therapeutic contact lens, but Tono-Pen was equally inaccurate with and without lenses, giving false low measurements. PMID- 1424646 TI - Effects of increasing Dk with rigid contact lens extended wear on rabbit corneal epithelium using confocal microscopy. AB - The effects of 24-h wear of various Dk-rigid gas-permeable (RGP) contact lenses on the rabbit corneal epithelium were studied by in vivo tandem scanning confocal microscopy (TSCM), and confirmed by scanning electron microscopy (SEM). Lenses used were polymethylmethacrylate (PMMA) (Dk/L = 0), RGP experimental A lens (siloxanylmethacrylate-fluoromethacrylate-methylmethacrylate , 33), experimental B (siloxanylmethacrylate-fluoromethacrylate, 56), and experimental C (siloxanylstyrene-fluoromethacrylate copolymer, 64 x 10(-9)) (cm/s) (ml O2/ml mm Hg) with 0.15-mm thickness (Dk/L measured by polarograph including boundary layer effect). After 24-h PMMA lens wear, TSCM showed no superficial epithelial cells but only exposed, underlying wing cells. The cornea with experimental A showed partial superficial epithelial desquamation. With experimental B wear, slight superficial epithelial cell swelling and desquamation were observed on the surface of the cornea. No changes were observed for the eye with experimental C and control. The observed severity of desquamation of superficial epithelial cells was dependent on the oxygen transmissibility (Dk/L) of RGP lenses worn. All in vivo findings were confirmed by SEM observations. Based on the results of this study, we conclude that (a) although Dk/L = 56 lens B shows no residual overnight corneal swelling, surface damage is still produced; (b) Dk/L = 64 lens C is best for epithelium showing the same corneal images as control; and (c) TSCM is a good way to evaluate the contact lens safety and efficacy in vivo at the cellular level noninvasively. PMID- 1424648 TI - Unpreserved carboxymethylcellulose artificial tears evaluated in patients with keratoconjunctivitis sicca. AB - In order to evaluate the therapeutic value of an unpreserved carboxymethylcellulose-based artificial tear in treatment of keratoconjunctivitis sicca (KCS), 56 patients with severe keratoconjunctivitis sicca were enrolled, at a single study center, in a randomized, double-masked, 8-week comparison with a preserved hydroxypropylmethylcellulose (HMC)-based artificial tear. Patients treated with the carboxymethylcellulose (CMC)-based tear showed significant improvement in fluorescein staining, symptoms, and impression cytology grades. Patients treated with HMC-based tears showed minimal improvement in a few variables. Impression cytology specimens were analyzed by a modified technique that maps the distribution of the various grades present on the specimen. With this technique, improvement in the cytology grades was noted in the group of patients using CMC-based tears. The improvement correlated with observed decreases in symptoms of discomfort and with scores for superficial punctate staining. This study supports the observed therapeutic value of unpreserved CMC based artificial tears and suggests the possible reversal of squamous metaplasia in patients with KCS. Further studies are required to separate the benefit of the CMC formulation from the benefits of preservative elimination. PMID- 1424647 TI - Ocular surface residence times of artificial tear solutions. AB - Solutions of hydroxypropylmethylcellulose (HPMC) and polyvinyl alcohol (PVA) are widely used as artificial tears. However, their usefulness is limited by the short duration of their effect. Dilute sodium hyaluronate (SH) solutions exhibit non-Newtonian rheology with high viscosities at low shear rates, which would be expected to enhance their ocular surface residence time. Using quantitative gamma scintigraphy, estimates of the ocular surface residence times of 0.3% HPMC, 1.4% PVA, and 0.2% SH were made in six patients with keratoconjunctivitis sicca. The sodium hyaluronate solution had a mean half-life on the ocular surface of 321 s, significantly longer than hydroxypropylmethylcellulose (44 s; p = 0.012) and polyvinyl alcohol (39 s; p = 0.013). PMID- 1424649 TI - Deep corneal scarring in pellucid marginal corneal degeneration. AB - Crescent-shaped, deep corneal scars were observed in seven (39%) of 18 patients with pellucid marginal corneal degeneration. The scars most likely represent a degenerative change related to the precipitous alteration in curvature of the cornea in that area. PMID- 1424650 TI - Epidermal growth factor and corneal wound healing. A multicenter study. AB - A randomized, double-blind, placebo-controlled, multicenter clinical trial was conducted in five centers to assess safety, ocular tolerance, and efficacy of an ophthalmic solution of epidermal growth factor (EGF) for the treatment of traumatic corneal epithelial defects. One hundred four patients completed the study: 47 received EGF and 57 placebo (the drug vehicle). Mean epithelial healing time was significantly enhanced in the EGF-treated group (44.17 h) compared with the placebo-treated treated group (61.05 h) (p < 0.01). The number of epithelial defects completely healed at 24, 48, and 72 h after the onset of treatment was significantly greater in the EGF-treated group. Local tolerance was adequate in both groups. These results indicated that topical EGF is well tolerated and may be a significant addition to the ophthalmologist's armamentarium for treating corneal epithelial defects. PMID- 1424651 TI - Two-dimensional gel electrophoretic comparison of endothelial cell-Descemet's membrane proteins in Fuchs' dystrophy and normal corneas. AB - Two-dimensional polyacrylamide gel electrophoresis was used to compare the proteins isolated from the combined corneal endothelial cell-Descemet's membrane complex of three pairs of corneas with Fuchs' dystrophy with three pairs of normal corneas. Normal or Fuchs' dystrophy endothelium and Descemet's membrane was documented by pathologic analysis of each cornea. Proteins were separated by isoelectric point in the first dimension and molecular weight in the second dimension. Over 300 proteins were resolved from each sample, and similar patterns were noted in both groups. No consistent differences were detected between the corneas with Fuchs' dystrophy and the normal corneas. Allelic variations of some proteins were detected in both groups. PMID- 1424652 TI - Reversible endothelial changes in the monkey cornea. AB - As part of a study examining the effects of contact lens extended wear in monkeys (Macaca fascicularis), reversible endothelial changes were observed in the cornea with slit lamp biomicroscopy and contact specular microscopy. These changes were associated with anterior eye inflammation in four monkeys (as occurs in humans). However, in two monkeys no obvious cause for these changes other than the presence of a contact lens on the cornea was apparent. In these two monkeys the endothelium displayed features similar to the transient endothelial bleb response, which has been observed only in humans. The monkey (M fascicularis) may thus be an appropriate model for further investigation of the endothelial response during anterior eye inflammation and the transient endothelial bleb response. PMID- 1424653 TI - Current practices in the prevention and treatment of corneal graft rejection. AB - Three hundred fourteen members of the Castroviejo Society were surveyed to determine current practices in the prevention and treatment of corneal graft rejection. One hundred thirty-seven responses were received and tabulated for routine postoperative prophylactic immunosuppression as well as treatment of epithelial rejection, endothelial rejection (three patterns), subepithelial infiltrates, acutely and progressively opacifying grafts without inflammation, and photophobia. All respondents applied topical steroids in the postoperative period, while about half also administered steroids subconjunctivally. For the treatment of obvious endothelial rejection, 100% of respondents used topical steroids, 57% used subconjunctival steroids, and 37% used systemic steroids. Prednisolone acetate, 1%, was the preferred topical preparation for all conditions (55-68% of respondents). Individual responses to the questionnaire showed a surprisingly wide variation in treatment preferences. PMID- 1424654 TI - Intraocular penetration of ketoconazole in rabbits. AB - We studied penetration of the antifungal agent ketoconazole into the cornea, aqueous humor, and vitreous of rabbits after topical, subconjunctival, and oral administration. The effect of debridement of corneal epithelium on penetration was also investigated. Ketoconazole levels in the cornea and aqueous humor were high after topical or subconjunctival administration, and increased markedly (especially in the cornea) if the corneal epithelium had been debrided before administration of the drug. For example, concentration of ketoconazole in the cornea 1 h after topical drug administration with or without complete corneal epithelial debridement was 44.0 +/- 10.1 and 1,391.5 +/- 130.0 micrograms/g, respectively. Drug levels in the vitreous were not detectable after topical or subconjunctival drug administration, but were improved slightly by prior epithelial debridement (8.3 and 0.12 micrograms/mL after 1 h, respectively). Orally administered ketoconazole resulted in high corneal concentrations (45.0 +/ 7.6 micrograms/g after 1 h) that were still substantial 24 h later (55.0 +/- 7.0 micrograms/g); levels in the aqueous were low. PMID- 1424655 TI - Age-related morphological changes in lid margin and meibomian gland anatomy. AB - Meibomian gland dysfunction (MGD) is responsible for recurrent irritative symptoms. Attempts to characterize MGD have largely concentrated on microbial and lipid abnormalities in meibomian gland secretions. Few reports describe histological abnormalities in this disease, and fewer still morphological changes. This article follows a previous study that established a classification for MGD. This was based on morphological changes in the meibomian gland and lid margin. Using this classification, we studied the age-related changes in 80 subjects, between 5 and 87 years of age without ocular disease. The lid margin became thicker after childhood. Lid margin vascularity and cutaneous hyperkeratinization increased with age in both lids, whereas, telangiectasia increased with age in the lower lid and squamous blepharitis and posterior lid margin rounding were more common after 50 years of age in the upper lid. Multiple rows of meibomian gland orifices occurred more frequently in the upper than lower lid, and orifice narrowing and pouting increased with age. No age-related changes in the shape or form of the mucocutaneous function, gland ducts, or acini were found. Meibomian gland secretions were less easily expressed in the elderly. We have attempted to define a normal range of lid morphology in healthy children and adults that we believe to be important for the subsequent definition of lid disease, and in particular, posterior blepharitis. PMID- 1424656 TI - Keratoconus and bilateral lattice-granular corneal dystrophies. AB - The occurrence of lattice and granular corneal dystrophies in the same eye has been reported in individuals who trace their families to the province of Avellino in Italy. We present the first histopathologic report of keratoconus and bilateral lattice-granular corneal dystrophies occurring in the same patient. This individual's family also originated in Avellino, Italy. PMID- 1424657 TI - Corneal topography of posterior keratoconus. AB - Posterior keratoconus is an unusual abnormality of the cornea generally classified as one of the anterior chamber cleavage anomalies. It is characterized clinically by the presence of a circumscribed or generalized corneal thinning with posterior depression of the cornea and is considered distinct from keratoconus. Although patients with posterior keratoconus may have visual complaints clearly related to their abnormal corneas, the surface topography of these corneas has not been studied in detail. Keratometry and photokeratoscopy provide an incomplete picture of the surface geometry of posterior keratoconus. We utilized computer assisted topographic analysis to study the cornea of a patient with posterior keratoconus. The Topographic Modeling System demonstrated that the patient's cornea showed a central steepened "cone" coincident with the area of circumscribed posterior keratoconus as well as paracentral flattening. This report documents the topographic abnormality in this rare disorder. PMID- 1424658 TI - Bacterial keratitis associated with vernal keratoconjunctivitis. AB - We cared for two patients with longstanding vernal keratoconjunctivitis who had bacterial corneal ulcers in each eye. Both patients were young, black, and had histories of atopy. The patients came for treatment with acute symptoms of pain, redness, and reduced vision in the affected eye. On examination in each case we found an epithelial defect associated with dense stromal infiltration, a calcific plaque in the bed of the ulcer, and a severe anterior chamber reaction, including a hypopyon in two cases. Cultures of corneal scrapings from all four eyes were positive for Staphylococcus aureus, and three of the four infections were polymicrobial. All four eyes responded rapidly to intensive topical antibiotic therapy, debridement of the calcific plaque, and subsequent treatment with topical corticosteroids and/or cromolyn sodium. Bacterial keratitis can occur in patients with vernal keratoconjunctivitis, especially those with vernal corneal ulcers. The abnormalities of ocular immune mechanisms found in patients with vernal keratoconjunctivitis may predispose them to bacterial keratitis. PMID- 1424659 TI - Persistent superficial punctate keratitis after resolution of chlamydial follicular conjunctivitis. AB - Two cases of follicular conjunctivitis due to Chlamydia trachomatis followed by punctate epithelial keratitis are described. Both cases were initially treated with either oral tetracycline or doxycycline with resolution of the follicles. These two patients subsequently had recurrent, bilateral grayish lesions at various levels in the corneal epithelium that stained in a punctate fashion with fluorescein. There was anterior stromal edema associated with some of these lesions in one case. The lesions were confined mostly to the central cornea. These recurrent lesions were unassociated with a conjunctival reaction, were unresponsive to oral tetracycline, but were exquisitely responsive to low doses of topical steroids. Chlamydial conjunctivitis and the associated keratitis typically shows no response or actual exacerbation of symptoms with topical steroids, and the keratitis shows a predilection for the upper half of the cornea. These patients demonstrate that chlamydial keratoconjunctivitis might result in a clinical appearance consistent with Thygeson's superficial punctate keratitis. PMID- 1424660 TI - Fixation forceps for corneal sections in cataract surgery. PMID- 1424661 TI - Ocular cicatricial pemphigoid in a twelve-year-old boy. PMID- 1424663 TI - Corneal toxicity study of two perfluorocarbon liquids in rabbit eyes. AB - Perfluorocarbon liquids are fully fluorinated, synthetic, transparent compounds with a high specific gravity. These compounds are being increasingly used as an intraoperative tool for repair of complicated retinal detachments. A potential complication of their use, however, is liquid entering the anterior chamber in aphakic patients. In the study described herein we evaluated the effects of two of these liquids when placed in the anterior chamber of the rabbit eye. Sixteen rabbit eyes underwent anterior chamber injection of 0.05 ml of either perfluoroctane, perfluoropolyether, or balanced salt solution (control eyes). Animals were monitored clinically by biomicroscopy and external photography for up to 14 days, after which they were sacrificed and the corneas processed for light and for scanning electron microscopy. The animals injected with perfluoropolyether showed more intense stromal inflammation and corneal vascularization (p less than 0.02) than did those that received perfluoroctane. However, the perfluoroctane group showed more of the "fish-egging" phenomenon (p less than 0.03). Loss of endothelial cells was similar in the two groups, as determined by light and scanning electron microscopy. These results suggest that the corneal toxicity of these two perfluorocarbon liquids is such that their use as vitreous substitutes should be limited to short-term replacement. PMID- 1424662 TI - Corneal storage medium preservation with defensins. AB - We used a synthetic defensin (rabbit neutrophil peptide-1; NP-1) as a microbicide in a corneal storage medium, Optisol without antimicrobial compounds. We established growth curves in Optisol for Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Each organism was evaluated separately at 4 degrees C, 23 degrees C, and 37 degrees C in Optisol with NP-1 at each of four different concentrations including 1, 10, 100, and 200 micrograms/ml. When the three organisms were evaluated in Optisol containing NP-1, we found that a concentration of 200 micrograms/ml of NP-1 successfully killed 99.9% (the limits of our assay) of all three organisms at all temperatures tested. We conclude that NP-1 exhibits promise as a nonantibiotic preservative agent in corneal storage media, since it was effective in killing organisms at all temperatures, including 4 degrees C. PMID- 1424664 TI - Effect of Harderian gland-derived growth factor on the growth of cornea stromal cells. AB - To investigate the physiological role of Harderian gland-derived growth factor (HGDGF), the effects of HGDGF and various other growth factors on the growth of cultured guinea pig cornea stromal cells were examined. HGDGF increased the incorporation of [3H]thymidine to 150% of the control (5% fetal calf serum). The combination of HGDGF with fibroblast growth factors (FGFs) or platelet-derived growth factor enhanced the cell growth over that of either growth factor alone, increasing the incorporation of [3H]thymidine to 180 and 190% of the control, respectively. The combination of HGDGF with transforming growth factor (TGF-beta) decreased the growth to 60% of the control, and epidermal growth factor had no effect on the activity of HGDGF. The growth-stimulating activity of HGDGF was inhibited by suramin in a different manner from that of FGFs. These findings suggest that HGDGF binds a specific cell-surface receptor and plays a role in the repair of injured parts of the cornea and in the maintenance of the cornea stromal cells. PMID- 1424665 TI - Isoelectric focusing pattern of human corneal aldehyde dehydrogenase. AB - The major soluble protein in the bovine cornea (BCP 54) has recently been identified as a class 3 aldehyde dehydrogenase. An enzymatic and even a possible structural role of this protein in the mammalian cornea has been proposed. Earlier we showed that the human cornea contains the same enzyme but with a different substrate specificity, compared to the bovine. Moreover, the enzymatic activity was harbored in the dimeric 88-kD species. Genetic variants have been found for several mammalian ocular aldehyde dehydrogenases. In this study we investigated whether such variants were also present in the human cornea by using a zymography technique for aldehyde dehydrogenase activity and immunoblotting with rabbit anti-BCP 54 and lectin staining after isoelectric focusing (IEF) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We investigated 50 individual human corneal epithelial extracts and found one common IEF variant (n = 47) and two "rare" IEF variants in three individuals. Analysis of these patterns indicates that the observed IEF profiles may be caused by posttranslational events. PMID- 1424666 TI - Fibrin-enmeshed tobramycin liposomes: single application topical therapy of Pseudomonas keratitis. AB - Treatment of bacterial keratitis requires frequent application of topical antibiotics. We studied the efficacy of a single topical administration of tobramycin incorporated in large multivesicular liposomes and enmeshed in a fibrin sealant on rabbit corneas infected with Pseudomonas aeruginosa. One cornea each of 25 New Zealand albino rabbits was infected with P. aeruginosa. Twenty four hours later, the animals were randomly divided into five groups of five. Group A received single hourly drops (50 microliters) of fortified tobramycin (14.5 mg/ml, total of 17.4 mg). Group B received a single topical application of 3.5 mg tobramycin, in 0.1 ml multivesicular liposomes, enmeshed in a fibrin sealant with an overlaying bandage contact lens. Group C was treated in the same manner as group B without the addition of fibrin sealant. Groups D and E served as nondrug-treated controls, with group D receiving topical fibrin-enmeshed liposomes devoid of tobramycin and group E receiving hourly topical balanced salt solution (BSS) drops. All animals were killed 24 h after initiation of therapy. Significantly fewer colonies of Pseudomonas were present in corneas of all three treated groups, as compared with the two nondrug-treated control groups (p less than 0.02). There were significantly fewer colonies of Pseudomonas in groups A and B as compared with group C (p less than 0.02). No significant difference was noted between a single administration of topical fibrinen-meshed tobramycin encapsulated liposomes (group B) and 24 doses of hourly fortified topical tobramycin (group A, p greater than 0.05). Tobramycin-encapsulated megaliposomes may serve as a useful adjunct in treatment of Pseudomonas keratitis. PMID- 1424667 TI - Anti-inflammatory therapy and outcome in a guinea pig model of Pseudomonas keratitis. AB - Corneal scarring as a consequence of bacterial keratitis is an important cause of visual loss and a major indication for penetrating keratoplasty. Anti inflammatory agents might be useful in this condition for limiting corneal damage, but benefit from adjunctive anti-inflammatory therapy has never been demonstrated. In this limited pilot study, we compared the effect on clinical outcome of treating Pseudomonas keratitis in guinea pigs with prednisolone (a corticosteroid), flurbiprofen (a cyclo-oxygenase inhibitor), nordihydroguaiaretic acid (a lipoxygenase inhibitor), and a leukotriene antagonist, SKF104353 [R-(R*, S*)]-beta-[(2-carboxyethyl) thio-alpha-hydroxy-2-(8-phenyloctyl) benzenepropanoic acid, zinc salt]. None of the anti-inflammatory agents prevented sterilization of ulcers with antibiotic (ofloxacin) therapy. Therapy with the leukotriene antagonist appeared to reduce infiltrate size more quickly and produce a more rapid reduction in lesion size, but the differences were not statistically significant. Sample size calculations suggest that very large numbers of animals would be required to prove efficacy. The role of anti-inflammatory agents in reducing the stromal destruction caused by bacterial keratitis remains controversial. PMID- 1424668 TI - Recurrence of microbial keratitis concomitant with antiinflammatory treatment in an animal model. AB - Recurrence of Pseudomonas keratitis during treatment with corticosteroids has been reported previously in humans. Rabbits with keratitis due to Pseudomonas aeruginosa or Streptococcus pneumoniae were treated with antibiotics and either vehicle, methylprednisolone acetate, flurbiprofen, or nordihydroguaiaretic acid (NDGA). Cultures performed after 7 days were negative, and antibiotics were discontinued. Two weeks later, Pseudomonas keratitis recurred in 6 of 7 (85.7%) steroid-treated rabbits, 1 of 8 (12.5%) flurbiprofen-treated rabbits, 1 of 8 (12.5%) NDGA-treated rabbits, and none of 8 vehicle-treated rabbits. None of the 31 rabbits infected with Streptococcus pneumoniae experienced recurrence. These data confirm the clinical observation that Pseudomonas keratitis may recur if antibiotic therapy is discontinued and corticosteroids are administered; the risk of recurrence appears to be much less with nonsteroidal antiinflammatory agents. PMID- 1424669 TI - Subconjunctival injection of purified blood mononuclear cells into alkali-injured rabbit eyes. AB - Monocytes transform into tissue macrophages that scavenge necrotic debris from wounds but also release substances stimulatory to fibroblasts. In an effort to encourage the healing process, monocytes, purified from rabbit blood, were injected subconjunctivally 1 or 2 days and 6 or 7 days after alkali injury to the rabbit eye. The injected monocytes failed to alter the course of the alkali injured eyes. Specifically, the incidence of corneal ulceration in the experimental group was not statistically different from that of the control group. A byproduct of this study was a presentation of the technique to purify platelet-free mononuclear leukocytes from rabbit peripheral blood. PMID- 1424670 TI - Inhibition of human corneal epithelium with immunotoxin 454A12-rRA. AB - We examined the effects of the immunotoxin 454A12-rRa on proliferating and confluent human corneal epithelium (HCE) in vitro. Proliferating HCE was sensitive to 454A12-rRA in a dose-dependent fashion. At immunotoxin concentrations of 1,000 ng/ml for 7 days we observed an 86% reduction in cell counts. Confluent HCE was not sensitive to 454A12-rRA at equivalent concentrations of immunotoxin. These data confirm previous observations regarding selective sensitivity of proliferating ocular tissue to immunotoxin, but suggest that HCE is less sensitive to 454A12-rRA than other ocular cell types. PMID- 1424671 TI - Cytologic evaluation of conjunctival epithelium after cataract surgery. AB - Although numerous studies have examined corneal epithelial wound healing, few reports describe conjunctival wound healing. Thus, we evaluated the conjunctival epithelium by brush cytology, in which a miniature brush was used to collect many cells relatively noninvasively. The temporal and superior conjunctivae were examined before and after cataract extraction on the first, third, seventh, and fourteenth days and then the first, second, and third months postoperatively, in a group of 20 patients (9 men and 11 women with a mean age of 69 years 3 months +/- 10 years). The cells collected were stained by the Papanicolaou method. Each postoperative specimen contained keratinized, polygonal, round, columnar, elongated, and inflammatory cells, as well as cells with nuclear alterations. No keratinized, elongated, or inflammatory cells were observed preoperatively. In contrast, columnar cells, which were present preoperatively, decreased during the wound healing process. Such nuclear changes as chromatin formation or the appearance of snake-like figures were observed in several patients postoperatively. These cellular changes may represent altered differentiation during the healing process. However, the conjunctival epithelium returned to normal within 2 months postoperatively in all patients. PMID- 1424672 TI - Risk factors for the development of postkeratoplasty glaucoma. AB - From a database of 1,122 penetrating keratoplasties performed under the care of the surgeons of the Corneal Clinic, Moorfields Eye Hospital (London, U.K.), 153 (14%) were identified as being complicated by postkeratoplasty glaucoma. The relative risk for its development varied with the indication for keratoplasty. Keratoconus had the lowest incidence along with some dystrophies, such as macular or granular dystrophy, and these were taken as the baseline for comparison. Anterior chamber dysgenesis syndromes had the highest risk among the indications for keratoplasty. Combined cataract or lens implant surgery was also found to be a risk factor, with anterior vitrectomy, anterior segment revision, and anterior chamber lens implant removal representing a greater risk than extracapsular extraction and posterior chamber lens implantation. Postkeratoplasty glaucoma was also strongly associated with peripheral anterior synechiae formation seen after keratoplasty. PMID- 1424673 TI - Ultrastructural effect of L-ascorbic acid 2-phosphate on cultured keratocytes. AB - I studied the effect of L-ascorbic acid 2-phosphate (P-Asc), a long-acting derivative of L-ascorbic acid, on the fine structures of cultured rabbit keratocytes. The results showed that cells cultured with 0.1 mM P-Asc for 30 days were more markedly multilayered than those grown without P-Asc. Dilation of the cisternae of the endoplasmic reticulum in the control cells indicated an accumulation of protein (probably procollagen). In addition, many lysosome-like structures, which may degrade underhydroxylated procollagen, were observed in the cytoplasm of the control cells. A slight increment of free ribosomes was also found within the control cells. P-Asc enhanced the multilayerization of cultured keratocytes. We conclude that the changes seen in the cytoplasm are due to the effect of P-Asc acting as vitamin C. PMID- 1424674 TI - Improved detection of disease progression in ocular cicatricial pemphigoid. AB - Cicatricial pemphigoid is an autoimmune systemic disease characterized by chronic conjunctival cicatrization. The natural history is one of variable degrees of progressive scarring of the ocular surface and visual loss. Previous reports have shown systemic chemotherapy to be efficacious in halting cicatrization in progressive cases. This observation makes it of critical importance to be able to detect progression of the disease as early as possible so as to allow for earlier institution of treatment. Our experience in previous studies has led us to believe that disease staging systems currently in use are relatively insensitive in detecting disease progression. We present a revised staging system that combines the strengths of the staging systems in use today and extends their sensitivity. PMID- 1424675 TI - A fish-eye disease-like familial condition with massive corneal clouding and dyslipoproteinemia. Report of clinical, histologic, electron microscopic, and biochemical features. AB - Fish-eye disease (FED) is a rare familial condition characterized by progressive bilateral corneal clouding and dyslipoproteinemia previously described in one family and an unrelated woman of Swedish descent. Biochemical studies have clearly demonstrated the existence of this entity as a unique dyslipoproteinemia. We present a non-Swedish family of Mediterranean ancestry afflicted with bilateral corneal clouding and lipoprotein analysis consistent with FED-like state. This family's biochemical profile, corneal button histology, and electron microscopy of one member are reviewed. Other dyslipoproteinemias causing corneal changes are considered. Corneal tissue and familial biochemical analyses differed significantly from previous descriptions. On the basis of these findings, explanation of pathologic deposition and disease mechanism is proposed. PMID- 1424676 TI - Corneal topographic changes over time after radial keratotomy. AB - Radial keratotomy flattens the cornea, but in a nonuniform fashion. We used computer-assisted topographic analysis to examine curvature changes in different regions of the cornea. Within 45 days after surgery in human eyes, the central and midperipheral cornea flattens and the periphery steepens. Shortly after surgery, the central cornea (within 1-1.5 mm of the corneal light reflex) is steeper than the adjacent midperipheral cornea (1.5-3 mm peripheral to the light reflex). With time, however, the central cornea flattens more than the midperiphery, such that it is no longer relatively steeper. This regional variability in corneal curvature after radial keratotomy helps explain phenomena such as multifocal lens effect after radial keratotomy, and the changes with time account for the conflicting results observed clinically in human corneas and experimentally in human eye bank eyes. PMID- 1424677 TI - Endothelial decompensation in a schizophrenic patient receiving long-term treatment with tranquilizers. AB - Bilateral corneal edema occurred in a schizophrenic patient receiving tranquilizers. This particular corneal edema was rapidly resolved after tranquilizer discontinuation. Specular microscopic examination disclosed marked enlargement of the corneal endothelium. This endothelial impairment may have been due to long-term administration of tranquilizers. PMID- 1424678 TI - Infectious crystalline keratopathy with ring opacity. AB - A 41-year-old physician was treated for 3 months with antiviral medications, antibiotics, and steroids for presumed herpetic keratitis. When seen by us, an annular infiltrate was observed, along with crystalline-like opacities in the superficial one third of the stroma. Cultures of scrapings and of subsequent biopsies were positive for Streptococcus mitis of the viridans group; histopathology demonstrated large aggregates of cocci between the stroma lamellae. Tapering of topical corticosteroids and treatment with topical penicillin resulted in resolution of the infiltrates. The clinical appearance and findings in this patient suggest that infectious crystalline keratitis can produce an annular infiltrate. Injection of the organism into rabbit corneas produced a crystalline infiltrate, but no annular opacity was observed. Corticosteroids altered the clinical and histopathologic appearance of the lesions in rabbits. PMID- 1424680 TI - Congenital hereditary corneal dystrophy: histologic and ultrastructural assessment of a peculiar polymorphic recessive form. PMID- 1424679 TI - Effects of viscoelastic solutions on neutrophil function and the release of neutrophil chemotactic factors from isolated bovine corneas. PMID- 1424681 TI - Mathematical analysis for rotating autokeratoplasty. PMID- 1424682 TI - Explanation. PMID- 1424683 TI - Grand challenges in biomedical computing. AB - Advances in computing technology (both algorithms and hardware) over the next several years promise to make increasingly sophisticated computer modeling of biomedical phenomena a routine part of biomedical research. Improvements in both the absolute speed of processors and in their programming and graphics interfaces will allow nonexpert users to bring computing power equivalent to the supercomputers of a few years ago to bear on routine research problems and to display complex data in understandable ways (visualization). Although biomedical applications have traditionally not driven the leading edge of computing and supercomputing, such applications are increasingly being ported to advanced parallel and vector processors. This paper summarizes the current state of biomedical computing, citing examples of the best practice in research today. A number of projects enabled by advanced computing from various subdisciplines are described. Trends in technology for both inexpensive (workstation) and high-end computing (vector supercomputers and parallel processors) are cited; the implications of these for biomedical computing are discussed. "Grand challenges" in biomedical computing, i.e., computational problems of major scientific importance that are beyond our current capabilities but that might be achieved in a 5-year time frame, are outlined. PMID- 1424684 TI - Skeletal muscle grids for assessing current distributions from defibrillation shocks. AB - This paper utilizes a structured and an unstructured grid representation of a torso with an anisotropic skeletal muscle to assess current distributions from defibrillation shocks. The results show that a finite-element solution on an unstructured grid of 400,000 elements (60,000 nodes) achieves comparable current distributions with a finite-difference solution on a structured grid that uses approximately the same number of nodes. Moreover, a finite-element solution on a 65,000-element (10,500 nodes) unstructured grid yielded fractional percent current results within 5% of the finer grids. The structured and unstructured grid models are used to investigate recent interpretations of experimental data that concluded that more than 80% of the total defibrillation current is shunted by the anisotropic skeletal muscle thoracic cage. It is concluded that these interpretations, which were based on a one-dimensional resistive network representation of the three-dimensional defibrillation situation, overestimate by 25% the current shunted by the anisotropic thoracic cage. PMID- 1424685 TI - The electrocardiographic inverse problem. AB - Using the boundary element method in conjunction with Tikhonov zero-order regularization, we have computed epicardial potentials from body surface potential data in a realistic geometry heart-torso system. The inverse reconstructed epicardial potentials were compared to the actual measured potentials throughout a normal cardiac cycle. Potential features (maxima, minima) were recovered with an accuracy better than 1 cm in their location. In this chapter, we use these data to illustrate and discuss computational issues related to the inverse-reconstruction procedure. These include the boundary element method, the choice of a regularization scheme to stabilize the inversion, and the effects of incorporating a priori information on the accuracy of the solution. In particular, emphasis is on the use of temporal information in the regularization procedure. The sensitivity of the solution to geometrical errors and to the spatial and temporal resolution of the data is discussed. PMID- 1424686 TI - Generalized approach to inverse problems in tomography: image reconstruction for spatially variant systems using natural pixels. AB - A major limitation in tomographic inverse problems is inadequate computation speed, which frequently impedes the application of engineering ideas and principles in medical science more than in the physical and engineering sciences. Medical problems are computationally taxing because a minimum description of the system often involves 5 dimensions (3 space, 1 energy, 1 time), with the range of each space coordinate requiring up to 512 samples. The computational tasks for this problem can be simply expressed by posing the problem as one in which the tomograph system response function is spatially invariant, and the noise is additive and Gaussian. Under these assumptions, a number of reconstruction methods have been implemented with generally satisfactory results for general medical imaging purposes. However, if the system response function of the tomograph is assumed more realistically to be spatially variant and the noise to be Poisson, the computational problem becomes much more difficult. Some of the algorithms being studied to compensate for position-dependent resolution and statistical fluctuations in the data acquisition process, when expressed in canonical form, are not practical for clinical applications because the number of computations necessary exceeds the capabilities of high-performance computer systems currently available. Reconstruction methods based on natural pixels, specifically orthonormal natural pixels, preserve symmetries in the data acquisition process. Fast implementations of orthonormal natural pixel algorithms can achieve orders of magnitude speedup relative to general implementations. Thus, specialized thought in algorithm development can lead to more significant increases in performance than can be achieved through hardware improvements alone. PMID- 1424687 TI - Structured and unstructured grid generation. AB - Current techniques in composite-block-structured grid generation and unstructured grid generation for general 3D geometries are summarized, including both algebraic and elliptic generation procedures for the former and Delaunay tessellations for the latter. Citations of relevant theory are given. Examples of applications for several geometries are included. PMID- 1424688 TI - Early increased gut permeability after burns. PMID- 1424689 TI - Undergraduate education in critical care medicine. PMID- 1424690 TI - Fulminant hepatic failure treated with anti-endotoxin antibody. PMID- 1424691 TI - Increased gut permeability early after burns correlates with the extent of burn injury. AB - OBJECTIVE: To determine if increased gut permeability within 48 hrs after burn injury correlates with the extent of injury, before sepsis and pulmonary disorders have complicated the clinical course. DESIGN: Nonrandomized, controlled study. PATIENTS: Consecutive patients admitted with burn injuries on > 20% of body surface area. INTERVENTIONS: Intestinal absorption and renal excretion of polyethylene glycol 3350 was used as the macromolecule to determine gut permeability; polyethylene glycol 400 intestinal absorption was used as an internal control for abnormal motility and malabsorption. Polyethylene glycol 3350 (40 g) and polyethylene glycol 400 (5 g) were administered enterally. MEASUREMENTS AND MAIN RESULTS: Gut permeability was significantly increased early after the injury. The patients excreted 0.56 +/- 0.34% (n = 11) of polyethylene glycol 3350, compared with the amount (0.12 +/- 0.04%) (p < .05) previously reported in normal volunteers. There was no significant difference in the excretion of polyethylene glycol 400 in the patients (27.0 +/- 4.6%, n = 11) vs. the normal volunteers previously reported (26.3 +/- 5.1%, n = 12), suggesting normal intestinal motility and absorption. The percentage of excretion of polyethylene glycol 3350 correlated with the percentage body surface burned; patients with smaller injuries excreted 0.32 +/- 0.17% (n = 6), which was greater than normal and less than those values from patients with larger injuries, 0.84 +/- 0.25% (n = 5) (p < .001 by Turkey test). CONCLUSIONS: Using our newly developed method to separate and quantify polyethylene glycols in urine, gut permeability was found to be increased early after burn injury, which confirms a previous study using lactulose as the permeability probe. Furthermore, this increased gut permeability to polyethylene glycol 3350 correlated with the extent of the burn injury. PMID- 1424692 TI - Value of postprocedural chest radiographs in the adult intensive care unit. AB - OBJECTIVE: To evaluate the necessity for postprocedural chest radiographs after catheterization of central veins, insertion of pulmonary artery catheters, and placement of endotracheal tubes. DESIGN: Prospective, controlled study. SETTING: Two academic tertiary adult ICUs. PATIENTS: Consecutive patients (n = 316) requiring central vein cannulation or endotracheal intubation in the ICUs. INTERVENTION: After each invasive procedure, the physician was instructed to complete a detailed evaluation sheet. Criteria based on the details of the procedure and immediate postprocedural clinical evaluation of the patient were used to determine the likelihood of a radiologically detectable complication. Actual radiologic findings were subsequently compared against clinical predictions. MAIN OUTCOME MEASUREMENTS: Ability of housestaff to correctly predict the absence of radiologically detectable postprocedural complications (predictive negatives). RESULTS: Ability to predict the absence of complications after cordis catheter insertions via the subclavian vein or internal jugular vein was very high (151/152; p < .001). Unsuspected complications were more frequent with central vein multilumen catheter insertions (3/24; p < .001). Ability to predict uncomplicated pulmonary artery catheterization was also high (110/111; p < .001). Physicians were unable to predict the majority of complications associated with endotracheal intubations (28/32; p > .50). CONCLUSIONS: The use of a protocol that includes an evaluation of the characteristics of the procedure and postprocedural physical examination can greatly reduce the need for routine chest radiographs after subclavian and internal jugular vein cordis catheterizations and pulmonary artery catheter placement. Chest radiographs should be performed after endotracheal intubation and multilumen catheter insertion. PMID- 1424693 TI - Prevalence of, and risk factors for, upper gastrointestinal tract bleeding in critically ill pediatric patients. AB - OBJECTIVE: To determine the occurrence of, and risk factors for, the development of upper gastrointestinal (GI) tract bleeding in critically ill pediatric patients. DESIGN: Prospective, descriptive, comparative study. SETTING: ICU in a tertiary care pediatric hospital affiliated with a university. PATIENTS: All patients < 19 yrs of age who were admitted to the ICU for a 4-month period (n = 429) were eligible for inclusion. A total of 221 patients were excluded for reasons listed below. Thus, 208 patients were studied. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated for overt upper GI bleeding as indicated by coffee ground material or bright red blood in gastric aspirates or black, tarry stools. Excluded were patients who were transferred out of the ICU within 24 hrs of admission, were receiving medications that would alter their risk for upper GI bleeding, or had a GI tract surgical procedure. Patients were categorized by diagnoses and analyzed for relative risk for upper GI bleeding. Of the 208 patients included, 25% had evidence of upper GI bleeding. There was no association between upper GI bleeding and age, weight, race, or sex. Diagnoses independently associated with an increased risk for upper GI bleeding were: circulatory shock, an operative procedure > or = 3 hrs in duration, and trauma. No clinically important sequelae were directly attributable to upper GI bleeding in this group of patients; however, intervention with antacids and histamine-2 receptor (H-2) antagonists likely decreased the progression of GI bleeding. CONCLUSIONS: Overt evidence of upper GI bleeding is not uncommon in critically ill pediatric patients. Certain diagnoses or risk factors may predispose these patients to develop upper GI bleeding. PMID- 1424694 TI - Thermodilution right ventricular ejection fraction measurement reproducibility--a study in patients undergoing coronary artery bypass graft surgery. AB - OBJECTIVE: To assess the effects of heart rate, right ventricular systolic performance (ejection fraction), chamber dimensions, and flow rate (cardiac index) on the reproducibility of algorithm-derived triplicate thermodilution right ventricular ejection fraction measurements. DESIGN: Prospective study; combined hemodynamic and echocardiographic clinical evaluation. SETTING: Operating room in a university hospital. PATIENTS: Twenty-one coronary artery bypass graft patients. MEASUREMENTS AND MAIN RESULTS: The right atrial delivery site was positioned by analysis of transduced pressure waveform and echocardiographic imaging of tracer agitated saline cavitations. Measurement reproducibility was quantified by determining the variation (standard deviation) within 101 triplicate thermodilution measurement sets. There was no significant relationship between measurement reproducibility and estimates of right atrial area (21.6 +/- 6.9 cm2), diameter (5.1 +/- 0.8 cm) and supero-inferior length (5.1 +/- 0.9 cm) and right ventricular maximal minor axis diastolic diameter (4.21 +/- 1.05 cm). Reproducibility was also unrelated to right ventricular end diastolic volume index (97.9 +/- 32.7 mL/m2) and cardiac index (2.9 +/- 0.9 L/min/m2). Measurement reproducibility was directly related to mean right ventricular ejection fraction (0.39 +/- 0.14) and inversely related to heart rate (80.8 +/- 18.6 beats/min) (p < .01 and < .001, respectively). CONCLUSIONS: Thermodilution-derived right ventricular ejection fraction measurement reproducibility was unrelated to estimates of right atrial and ventricular dimensions and cardiac index. Measurement reproducibility was a direct function of right ventricular systolic performance and an indirect function of heart rate. Measurement should be interpreted with these constraints in mind. PMID- 1424695 TI - Right ventricular systolic time intervals determined by means of a pulmonary artery catheter. AB - OBJECTIVES: To evaluate the right ventricular systolic time interval as an index of right ventricular function and also to ascertain whether the right ventricular ejection fraction may be determined by means of a conventional pulmonary artery catheter. DESIGN: Prospective study. SETTING: Intensive care unit. PATIENTS: Eight, consecutive critically ill adult patients. METHODS: Simultaneous blind measurements, performed by two investigators, of the right ventricular systolic time interval and right ventricular ejection fraction, determined by means of a pulmonary artery catheter. Two studies, separated by an interval of 24 hrs, per patient. Linear regression analysis. Multiple regression test. RESULTS: Of the 16 studies performed, two determinations of right ventricular systolic time intervals were technically inadequate. In the remaining 14 valid studies, we found one close linear correlation between the right ventricular ejection fraction and the preejection period/ejection time quotient measured using the simultaneous display of the electrocardiogram (EKG) and pulmonary arterial pressure curve (r2 = .90, p < .001, right ventricular ejection fraction = 68.96 60.59 x [right ventricular preejection period/right ventricular ejection time]). The method proved to be simple, very accurate, with little interobserver variation (8.09 +/- 10.6% interobserver variation for right ventricular preejection period/right ventricular ejection time) and provided adequate information regarding situations in which the performance of the right ventricle is modified in a given patient. The right ventricular preejection period/right ventricular ejection time quotient was the only variable that displayed a significant relationship with the right ventricular ejection fraction in the multivariate analysis (p < .001). CONCLUSIONS: Right ventricular systolic time intervals, measured using the simultaneous display of the pulmonary artery catheter curve and EKG, provide adequate information regarding right ventricle performance in critically ill patients. The close linear correlation between the right ventricular preejection period/right ventricular ejection time quotient and the right ventricular ejection fraction enables the investigator to estimate, with a high degree of accuracy, the right ventricular ejection fraction and the values derived from the preload of the right ventricle, without the need for a modified pulmonary artery catheter. PMID- 1424696 TI - Experience with hemoperfusion for organophosphate poisoning. AB - OBJECTIVE: To evaluate the usefulness of extracorporeal clearance techniques in the treatment of organophosphate poisoning, particularly hemoperfusion. DESIGN: Retrospective study. SETTING: An ICU of a general hospital. PATIENTS: Ten patients with organophosphate poisoning initially received classic treatment with gastric lavage and washing of the whole skin surface, as well as the administration of cathartics, activated charcoal, atropine, and obidoxime or pralidoxime. All patients underwent one to three hemoperfusions. MEASUREMENTS AND MAIN RESULTS: Plasma insecticide concentrations and cholinesterase activity were determined daily. Two to three biopsies of fat tissue were carried out at 1- to 2 wk intervals. The amount of the insecticide removed during hemoperfusions was also determined. Five patients presented with a prolonged nicotinic syndrome. Two of these patients showed sequelae of delayed neurotoxicity. Another two of the five patients died and the remaining patient recovered without sequelae. In none of the patients could > 0.1% of the total absorbed poison be removed by hemoperfusion. No changes in symptoms were observed after these procedures. Fat tissue concentrations of the insecticide were 20 to 50 times higher than the concentrations in plasma. Atropine decreased the intestinal transit time, and 10 days after poisoning, a powerful cathartic treatment indicated the persistence of gut content, which probably caused prolonged absorption of the toxin. CONCLUSIONS: Extracorporeal cleansing mechanisms did not remove any clinically important amount of insecticide from our patients due to the high lipid solubility of these agents and no changes in symptoms were observed after these methods. The use of atropine decreases bowel peristalsis. Early use of powerful cathartics could avoid protracted absorption of the poison stored in the gut, although the potential benefits of this therapy require confirmation by the performance of prospective, controlled investigations. PMID- 1424697 TI - Bacterial and fungal colonization of endotracheal tubes in children: a prospective study. AB - OBJECTIVES: To evaluate both the frequency and route of endotracheal colonization of intubated children by pathogens and to assess the usefulness of Pediatric Risk of Mortality scoring and measurement of gastric pH in predicting this colonization. DESIGN: Prospective data collection. SETTING: A multidisciplinary pediatric ICU. PATIENTS: Nineteen children with medical/surgical problems who were intubated for at least 4 days. INTERVENTIONS: Buccal mucosa, and endotracheal and gastric aspirates were cultured for pathogens immediately after endotracheal intubation and daily for 4 to 5 days. Pediatric Risk of Mortality scores were calculated at the time of endotracheal intubation; gastric pH was measured each time that the cultures were obtained. MEASUREMENTS AND MAIN RESULTS: The buccal mucosae of ten (53%) of 19 children were colonized with Candida species at the time of endotracheal intubation. This colonization correlated with the degree of physiologic instability as measured by Pediatric Risk of Mortality scores (12.9 +/- 2.8 SEM for those patients colonized vs. 4.9 +/- 1.0 for those patients not colonized; p = .01), but not with preintubation antibiotic therapy. Eleven (58%) children acquired 27 endotracheal pathogens after the day of intubation. The buccal mucosa was the initial site of colonization of 19 (70%) of 27 of the acquired pathogens. A gastric pH of > 3.0 at the time of intubation correctly predicted colonization in nine of 11 children (p < .025, Fisher's exact test); a Pediatric Risk of Mortality score of > 8 at the time of endotracheal intubation correctly predicted colonization in eight of 11 patients (p < .05, Fisher's exact test). CONCLUSIONS: Colonization of the buccal mucosa appears to be the crucial antecedent to endotracheal colonization in children. In children, gastric pH and Pediatric Risk of Mortality scores at the time of endotracheal intubation can predict pathogenic endotracheal colonization within 4 days of intubation. Selective decontamination regimes may be appropriate for these patients, especially those regimes that are directed to the buccal mucosa. PMID- 1424698 TI - Oxygen consumption, energy expenditure, and substrate utilization after cardiac surgery in children. AB - OBJECTIVE: To determine the oxygen consumption (VO2), resting energy expenditure, and substrate utilization after cardiac surgery in children. DESIGN: Prospective, observational, cross-sectional study with factorial design. SETTING: Pediatric ICU at a university hospital. PATIENTS: Twenty-six consecutive children during the first 3 days after open-heart surgery. INTERVENTIONS: Patients were mechanically ventilated and received routine therapeutic interventions. MEASUREMENTS AND MAIN RESULTS: VO2, resting energy expenditure, and substrate utilization were determined by indirect calorimetry. Cardiac index was calculated using the Fick equation from the measured VO2 and the arterial-mixed venous oxygen content difference, and this cardiac index value was compared with a simultaneous cardiac index value that was measured by thermodilution whenever possible. There were excellent correlation and agreement between cardiac index measurements by Fick equation and thermodilution, indicating accurate VO2 measurements. VO2 was consistent with predicted values in healthy resting children. Resting energy expenditure was consistent with the predicted basal metabolic rate. The mean caloric intake was 19% of the mean energy expenditure. The respiratory quotient was 0.74 +/- 0.05. The substrate utilization showed a shift toward fat oxidation and either gluconeogenesis or impaired carbohydrate utilization. CONCLUSIONS: Cardiovascular surgery in children does not significantly alter resting energy expenditure but influences the substrate utilization. Perioperative hormonal stress responses and therapeutically administered catecholamines may explain the shift toward fat oxidation. PMID- 1424699 TI - Intensive care treatment of patients with bleeding esophageal varices: results, predictors of mortality, and predictors of the adult respiratory distress syndrome. AB - OBJECTIVES: To determine the factors predicting mortality from bleeding esophageal varices and to examine the possibility of an association between the development of adult respiratory distress syndrome (ARDS) and the use of ethanolamine oleate as an esophageal variceal sclerosant. DESIGN: Retrospective review. SETTING: ICU in a teaching hospital. PATIENTS: A total of 101 patients with endoscopically confirmed bleeding esophageal varices were admitted on 124 occasions from 1985 to 1990. Mean age was 50 +/- 13.5 (SD) yrs. There were 62 males and 39 females. Using the Child-Pugh classification, 21.8% patients were class A, 38.6% class B, and 39.6% class C. Mean ICU and hospital lengths of stay were 5.4 +/- 5.1 and 19.6 +/- 16.1 days, respectively. Mean Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission was 16.5 +/- 7.6. INTERVENTIONS: Endoscopic variceal sclerotherapy was performed in 99 (79.8%) of 124 ICU admissions in the 101 patients. Esophageal balloon tamponade was performed in 64 (51.6%) and a vasopressin infusion was administered in 47 (37.9%) of the 124 ICU admissions. A variety of factors was studied to find predictors of mortality and the development of ARDS. RESULTS: Forty-eight (48.5%) of the 101 patients died during the hospital stay. Independent predictors of mortality (by stepdown logistic regression) were total volume of ethanolamine oleate injected during sclerotherapy, multiple blood transfusions, Glasgow Coma Scale score, International normalized ratio for prothrombin test, and the presence of circulatory shock on ICU admission. Age, sex, Child-Pugh score, APACHE II score, serum bilirubin, albumin, and creatinine concentrations, use of esophageal balloon tamponade or vasopressin infusion, sepsis, pneumonia, congestive cardiac failure, aspiration, and ARDS were not statistically independent predictors of outcome. There was no difference in the mortality rates for the various causes of liver disease. Pulmonary complications occurred in 44 (43.6%) patients; sepsis occurred in 31 (25%) patients. ARDS developed in 14 patients (11.3% admissions, 13.9% patients). Statistically independent predictors of ARDS were sepsis, low plasma albumin concentration, use of esophageal balloon tamponade, and more than one sclerotherapy session. The volume and type of sclerosant used were not statistically independent predictors. CONCLUSIONS: Outcome is poor for patients with bleeding esophageal varices requiring ICU admission and is related to the severity of liver failure, the degree of blood loss, and failure of therapy to stop the bleeding. The findings do not support an association between the use of the sclerosant ethanolamine and the development of ARDS. PMID- 1424700 TI - Bulk diffusion apnea test in the diagnosis of brain death. AB - OBJECTIVE: To assess the efficacy of bulk diffusion in maintaining oxygenation during apnea testing for brain death. DESIGN: Case series. SETTING: ICU in a primary care hospital. PATIENTS: Twenty-four consecutive patients with suspected brain death. Most patients suffered cerebral trauma from vehicular accidents. INTERVENTION: Patients were preoxygenated with an FIO2 of 1.0 and were maintained during apnea testing with bulk flow of an FIO2 of 1.0 at 40 to 60 L/min in adults and 15 L/min in children. The pre-apnea PaCO2 was between 35 to 45 torr (4.7 to 6.0 kPa) in all patients. MAIN OUTCOME MEASURES: Twenty-three patients completed the test. Five patients had a PaO2 < 100 torr (< 13 kPa) during the 10-min ventilator withdrawal time period. MAIN RESULTS: No patient breathed spontaneously during the apnea test. Twenty-two patients achieved a PaCO2 > 60 torr (> 8 kPa). One patient had a postapnea PaCO2 of 59 torr (7.8 kPa). The test was stopped in one patient who became hypotensive. CONCLUSIONS: The bulk diffusion technique has several advantages, including ease of performance over other methods of supplying oxygen during apnea testing, but this method does not prevent hypoxemia in patients with lung disease. PMID- 1424701 TI - Nitric oxide synthesis serves to reduce hepatic damage during acute murine endotoxemia. AB - BACKGROUND AND METHODS: Nitric oxide synthesis occurs both in vitro and in vivo in response to inflammatory stimuli and can have profound effects on the local cellular environment. Hepatocytes, Kupffer cells, and endothelial cells produce nitric oxide in vitro, but the in vivo role of this reactive mediator in the liver is unknown. We assessed the role of nitric oxide synthesis during endotoxemia in mice by inhibiting its synthesis with NG-monomethyl-L-arginine after lipopolysaccharide injection and by determining the effects of this inhibition on hepatic damage. RESULTS: Injection of lipopolysaccharide in mice increased plasma nitrite and nitrate concentrations, the stable end products of nitric oxide metabolism, and caused mild hepatic damage as measured by increased circulating hepatocellular enzyme levels. NG-monomethyl-L-arginine decreased plasma nitrite and nitrate values, but increased the lipopolysaccharide-induced hepatic injury. NG-monomethyl-L-arginine caused no hepatic damage when given without lipopolysaccharide. The extent of hepatic damage with NG-monomethyl-L arginine was proportional to the dose of lipopolysaccharide used and could be reduced with concurrent administration of L-arginine but not D-arginine. CONCLUSIONS: Nitric oxide synthesis provides a protective function against lipopolysaccharide-induced liver injury that increases in importance as the degree of endotoxemia increases. The production of nitric oxide is, therefore, an important part of the liver's response to a systemic inflammatory stimulus. PMID- 1424702 TI - Effect of extracorporeal membrane oxygenation on cerebral hemodynamics in newborn lambs. AB - BACKGROUND AND PURPOSE: Neurologic injury caused by changes in cerebral blood flow is a concern in infants treated with extracorporeal membrane oxygenation (ECMO). To investigate the hypothesis that cerebral hemodynamics would be influenced by bypass flow rates, eight ketamine anesthetized lambs (age range 1 to 8 days) had measurements of cerebral hemodynamics before and after institution of venoarterial bypass. METHODS: Cerebral blood flow (whole brain and regional) were measured using the radiolabeled microsphere technique. A left carotid artery catheter (placed without sacrificing the vessel) reference sample was used for calculation of brain blood flows. Arterial and venous (sagittal sinus) oxygen contents and blood gases were measured across the cerebral circulation. Cerebral oxygen consumption, oxygen delivery, and fractional oxygen extraction were calculated. Measurements were made pre-ECMO and after placement on venoarterial ECMO at flow rates of 50 and 100 mL/kg/min. In addition, four other lambs were studied at a flow rate of 150 mL/kg/min, and seven additional animals were used to address methodologic issues with the microsphere technique in this model. RESULTS: Cerebral blood flow and oxygen delivery significantly decreased, compared with control at both flow rates of 100 and 50 mL/kg/min (87.8 +/- 5.2 vs. 36.4 +/- 6.2; and 35.1 +/- 5.8 mL/100 g/min; 5.82 +/- 0.37 vs. 2.14 +/- 0.35; and 2.19 +/- 0.39 microM/100 g/min, respectively). Cerebral fractional oxygen extraction increased significantly at a flow of 50 mL/kg, and cerebral oxygen consumption decreased significantly at a flow of 100 mL/kg. At a flow rate of 150 mL/kg/min, cerebral hemodynamic variables did not differ from control measurements. CONCLUSIONS: These findings demonstrate that changes in cerebral blood flow and cerebral oxygen metabolism can occur in the newborn lamb with the initiation of ECMO, and that these changes are dependent on bypass flow rate. PMID- 1424703 TI - Epinephrine blood concentrations after peripheral bronchial versus endotracheal administration of epinephrine in dogs. AB - BACKGROUND AND METHODS: Emergency endotracheal drug administration has become an acceptable route for drug delivery during cardiopulmonary resuscitation. The purpose of the present study was to determine whether the site of endotracheal epinephrine injection is an important factor in its absorption. Epinephrine (1:1000), in a dose of 0.02 mg/kg diluted in 2 mL of saline, was given to ten anesthetized mongrel dogs. Each dog was studied twice: once when the epinephrine was injected into the endotracheal tube, and on another day, through the endotracheal tube via a flexible catheter wedged into a peripheral bronchus. Arterial blood samples for plasma epinephrine concentration determinations were collected, before and at 1, 2, 5, 10, 15, and 30 mins after each intratracheal drug administration. RESULTS: Both routes of epinephrine administration significantly increased plasma concentrations within 1 min of injection. Higher plasma epinephrine concentrations were achieved after peripheral bronchial epinephrine administration (maximal concentration 8.9 +/- 3.2 vs. 2.0 +/- 0.4 ng/mL), and the total dose absorbed was significantly (76.5 +/- 13.5 vs. 36.7 +/- 6.5 ng/min/mL, p < .05) higher. The time interval to reach maximal concentration was significantly shorter with the peripheral bronchial dosing than with the endotracheal route (1.3 +/- 0.2 vs. 2.7 +/- 0.5 min, p < .05). Neither group demonstrated a significant change in heart rate, and both had similar, minor decreases in BP for > 2 to 5 mins. There were no significant differences between the arterial blood gases of the two groups at various stages of the experiment. CONCLUSIONS: In dogs, epinephrine administered via the peripheral bronchial route has a clear pharmacologic advantage over the endotracheal route. This advantage may be more important during cardiopulmonary resuscitation conditions and other low flow states, and may account for the failure observed with the endotracheal route in recently published clinical reports. PMID- 1424704 TI - Hyperbaric oxygen therapy accelerates neurologic recovery after 15-minute complete global cerebral ischemia in dogs. AB - BACKGROUND AND METHODS: Although hyperbaric oxygen therapy is clinically used for the treatment of several types of ischemic brain injury, few basic animal studies are available that provide a rationale for this therapy for complete global brain ischemia. Therefore, we investigated the effect of hyperbaric oxygen therapy on neurologic recovery after 15-min complete global cerebral ischemia in a canine model. Complete global ischemia was induced in 19 dogs by occlusion of the ascending aorta and the caval veins. Nine dogs were randomized to treatment with hyperbaric oxygenation (3 atmospheres absolute, 100% oxygen for 1 hr) at 3, 24, and 29 hrs after ischemia under spontaneous respiration, while the other ten dogs served as the control group without hyperbaric oxygen therapy (group C). Neurologic recovery was evaluated based on the electroencephalogram (EEG) activity score (1 = normal; 5 = isoelectric) and the neurologic recovery score (100 = normal; 0 = brain death) over a 14-day postischemic period. RESULTS: The survival rates were 3/10 (30%) in the control group vs. 7/9 (78%) in the group treated with hyperbaric oxygen (p < .05). Over the 14-day postischemic period, the best (lowest) EEG scores of each dog were significantly (1.7 +/- 0.2 vs. 2.9 +/- 0.3; mean +/- SE, p < .01) lower in the hyperbaric oxygen-treated group. The best neurologic recovery scores of each dog were significantly (69 +/- 6 vs. 48 +/- 5; mean +/- SE, p < .05) higher in the treated animals. The number of dogs that recovered to a neurologic recovery score of > 65 (assessed as a slight disability) were 1/10 in the control group and 6/9 in the group treated with hyperbaric oxygen (p < .02). CONCLUSIONS: Hyperbaric oxygen therapy performed in the early postischemic period accelerated neurologic recovery and improved the survival rate in dogs after 15-mins of complete global cerebral ischemia. PMID- 1424705 TI - Undergraduate education in critical care medicine. AB - OBJECTIVE: To review the current status and future needs of medical students with respect to education in critical care medicine. DATA SOURCES: Literature review and questionnaire administered at the 1990 Educational and Scientific Symposium of the Society of Critical Care Medicine. MEASUREMENTS AND MAIN RESULTS: Medical students are presently not required to master even the basic aspects of critical care medicine before licensing. The results of the questionnaire demonstrated that critical care medicine professionals believe a critical care core curriculum should be established and its completion should be made a requirement for graduation from medical school. A reference set of critical care medicine learning objectives and a strategy for their implementation are presented. CONCLUSIONS: There is a gap between what student physicians are required to learn and what they need to know to effectively initiate critical care interventions and to appropriately refer patients to ICUs. This gap can and should be remedied with wide implementation of a critical care core curriculum. PMID- 1424706 TI - Mean airway pressure: physiologic determinants and clinical importance--Part 2: Clinical implications. AB - PURPOSES: To discuss the theoretical relationship of mean alveolar pressure to its most easily measured analog, mean airway pressure, and to describe the key determinants, measurement considerations, and clinical implications of this index. DATA SOURCES: Relevant articles from the medical and physiological literature, as well as mathematical arguments developed in this article from first principles. STUDY SELECTION: Theoretical, experimental, and clinical information that elucidates the physiologic importance, measurement, or adverse consequences of mean airway pressure. DATA EXTRACTION: Mathematical models were used in conjunction with data from the published literature to develop a unified description of the physiological and clinical relevance of mean airway pressure. SYNTHESIS: Geometrical and mathematical analyses demonstrate that shared elements comprise mean airway pressure and mean alveolar pressure, two variables that are related by the formula: mean alveolar pressure = mean airway pressure + (VE/60) x (RE - RI), where VE, RE, and RI are minute ventilation and expiratory and inspiratory resistances, respectively. Clear guidelines can be developed for selecting the site of mean airway pressure determination, for specifying technical requirements for mean airway pressure measurement, and for delineating clinical options to adjust the level of mean airway pressure. Problems in viewing mean airway pressure as a reflection of mean alveolar pressure can be interpreted against the theoretical basis of their interrelationship. In certain settings, mean airway pressure closely relates to levels of ventilation, arterial oxygenation, cardiovascular function, and barotrauma. Because mean airway pressure is associated with both beneficial and adverse actions, a thorough understanding of its theoretical and practical basis is integral to formulating an effective pressure-targeted strategy of ventilatory support. CONCLUSIONS: Mean airway pressure closely reflects mean alveolar pressure, except when flow resistive pressure losses differ greatly for the inspiratory and expiratory phases of the ventilatory cycle. Under conditions of passive inflation, mean airway pressure correlates with alveolar ventilation, arterial oxygenation, hemodynamic performance, and barotrauma. We encourage wider use of this index, appropriately measured and interpreted, as well as its incorporation into rational strategies for the ventilatory management of critical illness. PMID- 1424707 TI - Fulminant hepatic failure treated with anti-endotoxin antibody. PMID- 1424708 TI - Patient-controlled analgesia masking pulmonary embolus in a postoperative patient. PMID- 1424709 TI - Lethal catatonia and neuroleptic malignant syndrome. PMID- 1424710 TI - Prolonged paralysis after long-term vecuronium infusion. PMID- 1424711 TI - Effects of storage temperature on viable bioprosthetic heart valves. AB - Long-term in vivo success of bioprosthetic allografts is dependent upon retention of cellular functions, such as protein synthesis. The purpose of the experiments presented in this report was to determine the storage conditions necessary for retention of protein synthetic functions in human allograft heart valve leaflets. Tissue viability was assessed by measurement of tritiated-glycine incorporation into proteins. Comparison of short-term (less than 3 month)- and long-term (1 and 2 years)-cryopreserved heart valve leaflet storage in a liquid nitrogen freezer below -135 degrees C demonstrated preservation of fibroblast protein synthesis. In contrast, storage in a mechanical freezer at -80 degrees C resulted in a time dependent loss of fibroblast protein synthesis. There was no statistically significant effect on protein synthesis in leaflets stored for 1 week at 4 degrees C compared to control cryopreserved liquid nitrogen-stored leaflets. After 2 weeks of 4 degrees C storage leaflet protein synthesis declined significantly to 15% that of cryopreserved controls. These results demonstrate that liquid nitrogen storage of valve bioprostheses is required for long-term preservation of cellular functions. PMID- 1424712 TI - Parthenogenetic activation pattern and microtubular organization of the mouse oocyte after exposure to 1,2-propanediol. AB - We have studied the effect of 1,2-propanediol (PROH) on cumulus-oocyte complexes from the mouse. We determined the morphological survival rate, the pattern of parthenogenetic activation, and the microtubular and chromosomal organization. Cumulus-oocyte complexes were collected at 16 h post hCG from superovulated female hybrid mice. These cumulus-intact oocytes were exposed to 1.5 or 3 M PROH for 6, 12, or 18 min at 0, 22, or 37 degrees C. The cryoprotectant was diluted out in a 1 M sucrose solution at 22 degrees C. After 5-6 h at 37 degrees C, oocytes were denuded and examined under Nomarski optics. The results show that PROH can induce degeneration and parthenogenetic activation in the mouse oocyte in a concentration, temperature, and time-dependent way. As the activation stimulus was strengthened, an increasing proportion of oocytes shifted from parthenogenetic activation with polar body extrusion to parthenogenetic activation with polar body retention and even to immediate cleavage. Nontoxic and nonactivating conditions involved mainly exposure to 1.5 M PROH at 0 degrees C. Spindle integrity and chromosomal organization were analyzed for exposure to 1.5 and 3 M PROH for 12 min at 0 degrees C. The separate effect of cooling and exposure to 1 M sucrose were also evaluated. Microtubules were visualized by monoclonal anti-alpha-tubulin labeling followed by immunogold-silver staining. Cooling and exposure to 1 M sucrose or to 1.5 M PROH did not induce major abnormalities in the microtubular or chromosomal organization. On the other hand, a significant percentage of deformities such as spindle size reduction and loss of bipolarity were observed after exposure to 3 M PROH. The results of the present study demonstrate that the use of PROH as a single cryoprotectant for the freezing of mature unfertilized oocytes cannot be recommended in procedures involving ambient temperature or concentrations exceeding 1.5 M PROH. On the other hand, the potential beneficial effect of low temperatures may outweigh the effect of concentration at subzero temperatures and could be explored further in the tailoring of conditions for slow controlled freezing. PMID- 1424713 TI - Rheological measurements of the influence of 1,2-propanediol on actin/alpha actinin gel structure: the effects of temperature and protein concentrations. AB - In previous studies, we demonstrated that 1,2-propanediol induces shortening and bundling of actin filaments, both in vitro and in vivo, and that it enhances actin/alpha-actinin interaction, especially at low temperature. 1,2-Propanediol also promotes homogeneous microporous networks which can be vitrified by rapid cooling. In the present study, dynamical rheological measurements were performed under various sets of experimental conditions including temperature (4 or 20 degrees C), protein concentrations (actin and alpha-actinin), and 1,2-propanediol presence or absence. Gelation kinetics were monitored, and the resulting actin mechanical properties investigated, in order to untangle the respective effects of the experimental parameters. Whether in the presence or absence of solvent, low temperature brings about a rigidification of the sample, as does high protein concentration, as expected. However, 1,2-propanediol itself involves either softening of the sample (at high temperature and low protein concentration or at low temperature and high protein concentration) or rigidification in the case of low temperature and low protein concentration. These effects result from the competition between actin/alpha-actinin affinity (enhanced by both low temperature and 1,2-propanediol), bundling of filaments (fostered by alpha actinin for alpha-actinin/actin ratios used), rate of actin polymerization (higher at high temperature), shortening effect of 1,2-propanediol on actin filaments, and chain mobility (lower at high protein concentration). As discussed, only the combination of low temperature and low protein concentration induces full crosslinking of the system into a viscoelastic solid under the influence of 1,2-propanediol. PMID- 1424714 TI - Leakage of a trapped fluorescent marker from liposomes: effects of eutectic crystallization of NaCl and internal freezing. AB - Leakage of trapped carboxyfluorescein from DL-alpha dipalmitoylphosphatidylcholine multilamellar liposomes (diameter 1-2 microns) in NaCl solutions was measured after rapid freezing to temperatures between -15 and 55 degrees C. Leakage was low after freezing between -15 and -35 degrees C, but increased steeply between -35 and -45 degrees C. From DSC measurements it was found that the increase in leakage was associated with two crystallization processes: Eutectic crystallization of NaCl and freezing of undercooled solvent trapped in the interior of the liposomes ("internal freezing"). Damage caused by the former process could effectively be prevented by small amounts of trehalose (1% less than or equal to w less than or equal to 1.5%). Trehalose in these concentration also decreased damage due to internal freezing, but to a minor degree. In addition to these damaging transitions, a time-dependent process was found to cause leakage from the liposomes at -25 degrees C. The association between leakage and thermal activity suggests that DSC supplements cryomicroscopy and leakage measurements in the characterization of cryostability of liposomes. PMID- 1424715 TI - Critical cooling rates for aqueous cryoprotectants in the presence of sugars and polysaccharides. AB - The technique of isothermal emulsion differential scanning calorimetry was used to determine time-temperature-transformation (TTT) curves for aqueous glycerol and butane-2,3-diol in the presence of various polysaccharides and sugars. The critical cooling rate required to avoid the crystallization of ice in these solutions was then calculated from the experimental TTT curves. The polysaccharides used in this study included starch hydrolysis products and dextrans of various molecular weights. The sugars used here were sucrose, glucose, trehalose, and raffinose. The results show that the critical cooling rates of butane-2,3-diol and glycerol are reduced by varying amounts by the addition of such materials but that the reduction is not as great as is achieved by the addition of polyethylene glycol with a molecular weight of 400. PMID- 1424716 TI - Hydration of oligosaccharides: anomalous hydration ability of trehalose. AB - The disaccharide trehalose extensively exists in anhydrobiotic organism and is considered to play an important role in preserving the integrity of biomembrane. However, the preserving mechanism remains unclear. In this report, we examine the hydration abilities of trehalose and several oligosaccharides composed of alpha-D glucopyranosyl residues. The unfrozen water fraction per molecule was determined from differential scanning calorimetry measurements of their aqueous solutions. Further, the NMR relaxation time of the natural abundance 17O of water is measured for several saccharide solutions. These results indicate that trehalose has the highest hydration ability among the saccharides studied. In other words, trehalose can effectively lower the mobility of water molecules hydrogen-bonded with saccharides. It is thus reasonable that, among the disaccharides studied, trehalose exhibits the maximum stabilizing effect on the bilayer structure of lipid whose acyl chains are bonded with each other by the apolar interaction, because the apolar interaction is strengthened with the stabilization of the surrounding water structure. PMID- 1424717 TI - Hibernation alters the frog's immune system. AB - The lymphomyeloid organs and blood leukocyte populations of the leopard frog, Rana pipiens, undergo conspicuous changes during hibernation at 4 degrees C. Within the blood, spleen, thymus, jugular bodies, and bone marrow there was a progressive loss of hemopoietic populations resulting in a marked lymphocyte depletion. Termination of the 135-day hibernation period resulted in the restoration of all hemopoietic elements in the blood and lymphomyeloid organs within 30 days. Frogs subjected to experimental hibernation and immunized showed weakened immune responses when brought from the hibernaculum. Plaque-forming cells (PFC) were lower in spleen, jugular bodies, and bone marrow, and serum antibody titers were also lower. Although the kinetics of the primary responses were essentially the same, the secondary responses differed suggesting major rearrangements with respect to the numbers of cells and their function in secreting antibody. The apparent lymphocyte aplasia may contribute to the absence of immunological responsiveness during periods of hibernation. PMID- 1424718 TI - The influence of basic fibroblast growth factor on cat corneal endothelial wound healing in vivo. AB - Using standardized freeze wounds in cat corneas, we tested the efficacy of basic Fibroblast Growth Factor (bFGF) solubilized in phosphate buffered saline (PBS) to promote endothelial healing when injected intraocularly at doses ranging from 0.01 microgram to 10 micrograms. After 6 days, animals were humanely sacrificed and corneal tissues were fixed and stained for light microscopy and computation of remaining wound areas. A significant dose-response relationship was found between the dosages of 0.01, 0.1, and 1.0 microgram of bFGF/eye and the stimulation of more completely healed endothelium six days after transcorneal freeze wounding. Significantly larger endothelial wounds were present six days after wounding when the eyes were treated with 10 micrograms of bFGF/eye compared with controls treated with PBS only. PMID- 1424719 TI - Systemic and topical protection studies using Pseudomonas aeruginosa flagella in an ocular model of infection. AB - Purified flagella from P. aeruginosa ATCC 19660 were used for active, passive, or topical immunization prior to corneal challenge with strain 19660. At 30 days post-infection, a significant number of mice actively or passively immunized with flagella and infected with the homologous bacterial strain were protected from ocular disease when compared to control animals. In topical immunization studies, premixing of 19660 flagella with the bacterial inoculum prior to ocular challenge with strain 19660, provided results similar to those of the active or passive immunization studies. A reduced lipopolysaccharide (LPS:1 E.U./mg) flagella preparation was also produced and used similarly. Again, significant protection was achieved in mice immunized by flagella regardless of the immunization route. An in vitro adherence assay also was performed to examine quantitatively the effect of exogenously applied flagella, or an antiflagella monoclonal antibody (MAb) on bacterial adhesion. Premixing of the bacterial inoculum with flagella or the MAb prior to applying it topically to corneas in organ culture all significantly inhibited bacterial binding. These results strongly suggest that significant ocular protection is achieved with either active or passive immunization, or premixing of the bacterial inoculum with flagella from strain 19660 prior to ocular challenge with the homologous bacterial strain. They also indicate that topical application of flagella or antiflagella MAb provide protection against ocular disease by decreasing bacterial adhesion to cornea. PMID- 1424720 TI - Examination of a lens 'native' plasma membrane fraction and its associated crystallins. AB - A bovine lens "native" plasma membrane fraction containing its full compliment of extrinsic proteins was prepared by sucrose density centrifugation of the water insoluble fraction. The major membrane fraction was found at the 25/45% sucrose interface. This fraction contained 73% of the total water insoluble phospholipid, 74% of the total water insoluble cholesterol and 58% of the total urea-insoluble protein. Only 9% of the total urea-soluble protein was membrane associated (extrinsic protein), most (75%) was recovered from the pellet. The major intrinsic protein (8 M-urea-insoluble) of the membrane fraction was MIP28, with lesser amounts of MP17. Extrinsic proteins (8 M-urea-soluble) were examined by SDS-PAGE, isoelectric focusing, immunoblotting and amino acid composition analysis. Approximately 70% of the total extrinsic protein appeared to be alpha A crystallins and modified alpha A-crystallins. About 20% of the extrinsic protein was apparently beta- and gamma-crystallins. The remainder contained presumed cytoskeletal proteins and perhaps other unidentified polypeptides. The native plasma membrane was found distributed throughout the lens with only minor differences in the quantitative composition of the membrane fraction. We have concluded that the native membrane fraction represents the lens plasma membrane with its extrinsic proteins which exist in vivo. These extrinsic proteins appeared to be primarily acidic alpha-crystallin polypeptides with minor amounts of beta- and gamma-crystallins, and presumed cytoskeletal elements. We speculate that these extrinsic proteins may serve as a nucleation site for the association of other water insoluble protein through protein-protein interactions such as those found in the non-membrane associated urea-soluble protein. Together, these interactions may form a structured cytoplasmic matrix important for the maintenance of lens transparency. PMID- 1424721 TI - Proteoglycan synthesis by scleral chondrocytes is modulated by a vision dependent mechanism. AB - Proteoglycan synthesis was measured in chick sclera at the onset of form deprivation myopia, as well as in the period immediately following removal of the occluder. Two day-old chicks were monocularly form vision deprived for periods from one to ten days and proteoglycan synthesis was determined after placing posterior scleral buttons in organ culture and measuring 35SO4 incorporation into glycosaminoglycans. Following 24 hrs of form-deprivation, proteoglycan synthesis was 33% higher in myopic eyes as compared with paired control eyes. The rate of proteoglycan synthesis further increased to levels 83% higher than controls after four days of form-deprivation and remained elevated throughout the ten day period of deprivation. Removal of the occluder after 10 days of form-deprivation resulted in a rapid drop in the rate of proteoglycan synthesis to control levels within 24 hrs. Proteoglycan synthesis was also measured in scleral chondrocytes isolated from control and myopic eyes after 10 days of form-deprivation. Proteoglycan synthesis by chondrocytes from myopic eyes did not return to control levels until 48 hrs after plating. Since the rate of proteoglycan synthesis returns to control levels more quickly during the recovery period ex vivo than when scleral chondrocytes from myopic eyes are placed in cell culture, we suggest that a mechanism is present within the eye which rapidly lowers the rate of proteoglycan synthesis in response to form vision. PMID- 1424722 TI - Enrichment of polyunsaturated fatty acids from rat retinal pigment epithelium to rod outer segments. AB - Polyunsaturated fatty acids (PUFA), especially docosahexaenoic acid (DHA, 22:6n 3), are enriched in phospholipids of vertebrate rod outer segments (ROS). Retinal ROS can incorporate 22 carbon (C-22) PUFA from the plasma pool where C-20 PUFA are predominant. In this study, we analyzed the fatty acid composition of retinal pigment epithelium (RPE) and ROS from rats fed different fatty acid supplements to determine whether this enrichment is at the photoreceptor-RPE boundary or the RPE-choriocapillaris boundary. Long Evans rats were raised from birth for 13-14 weeks on a diet supplemented with 10% (wt/wt) hydrogenated coconut oil (COC; 0.2% 18:2n-6, no 18:3n-3), safflower oil (SAF; 73.8% 18:2n-6, 0.1% 18:3n-3), or linseed oil (LIN; 16.4% 18:2n-6, 52.2% 18:3n-3). These diets were chosen because they increased plasma levels of 20:3n-9, 20:4n-6, and 20:5n-3, respectively. These three fatty acids served as metabolic markers. Plasma levels of 22:6n-3 were reduced by the COC and SAF diets. The RPE incorporated 20:3n-9, 20:4n-6, and 20:5n-3 from the plasma. However, the levels of 20:3n-9 and 20:5n-3 were very low in ROS and 20:4n-6 was not significantly elevated in the ROS of the SAF diet group. The relative amount of total C-20 PUFA in phospholipids in RPE was similar to that found in plasma and was about 4-16 times (depending on different lipid classes) that in the ROS. In contrast, C-22 PUFA (22:6n-3 and 22:5n-6) showed a step-wise, average 3-5 fold increase in concentration from the plasma to the RPE to the ROS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424723 TI - Lipids of frog retinal pigment epithelium: comparison with rod outer segments, retina, plasma and red blood cells. AB - The glycerolipid and fatty acid compositions of frog retinal pigment epithelium (RPE) were determined and compared with rod outer segments (ROS), retina, plasma, and red blood cells (RBC). The glycerolipid class composition of RPE was similar to RBC and ROS or retina, with phosphatidylcholine and phosphatidylethanolamine being the major components. The fatty acid composition of RPE differed substantially from that of plasma or RBC; the former contained much higher levels of C-20 and C-22 polyunsaturated fatty acids (PUFAs), such as 20:4n-6 and 22:6n 3, but less C-18 mono-, dienoic, and trienoic acids. The difference between RPE and ROS or retina with respect to fatty acid profile was also dramatic; RPE had relatively less 22:6n-3, but more 20:4n-6 and 18:2n-6, than ROS or retina. These results suggest that frog RPE cells may selectively take up C-20 and C-22 PUFAs from the circulation, but preferentially deliver 22:6n-3 to the ROS and retina. Fatty acid analyses show that 20:4n-6 and 22:6n-3 were unevenly distributed among RPE glycerolipids; phosphatidic acid, diglyceride, triglyceride, and phosphatidylserine are relatively more enriched in 22:6n-3 compared with 20:4n-6. This information might imply that these two PUFAs are metabolized differently inside the frog RPE cells. PMID- 1424724 TI - Selective association of crystallins with lens 'native' membrane during dynamic cataractogenesis. AB - Plasma membrane with its associated extrinsic proteins was isolated from normal and cataractous rat lenses by centrifugation of the total water insoluble fraction from homogenized lenses on a discontinuous sucrose gradient. Membrane, which we call "native" membrane, was recovered mainly from the 25/45% sucrose interface. Development of the experimental U18666A cataract resulted in plasma membrane shifting to higher density (the 50/55% sucrose fraction) and great increases in the urea soluble protein content of the lens. At early stages of cataract development, most of the increased urea soluble protein was membrane associated, presumably as extrinsic protein. With advancing cataract, most of the urea soluble protein appeared in an essentially membrane-free pellet fraction. The urea soluble protein associated with the cataract membrane was shown by combined IEF, SDS-PAGE, Western blotting, amino acid compositional analysis and protein sequence determinations to be mainly composed of modified alpha- and beta crystallins. Alpha A-crystallin truncated by not more than 27 residues from the carboxyl terminus plus beta b1 crystallin truncated by 49 residues from the amino terminus were conclusively identified. In addition to beta b1, a population of six alpha-crystallin derived polypeptides were specifically enriched in the cataract membrane fraction. Four of these six alpha-crystallins appear to be truncated from their carboxyl terminus, a modification which should have increased their hydrophobicity. The pellet fraction, which accumulated in the lens nucleus as the cataract advanced, was enriched in urea soluble gamma crystallin derived polypeptides. We suggest that protein insolubilization in this experimental cataract involves the selective and tight association of principally modified alpha-crystallins to the fiber cell plasma membrane. PMID- 1424725 TI - The ability of lens alpha crystallin to protect against heat-induced aggregation is age-dependent. AB - Alpha crystallin was prepared from newborn and aged bovine lenses. SDS-PAGE and tryptic peptide mapping demonstrated that both preparations contained only the alpha-A and alpha-B chains, with no significant contamination of other crystallins. Compared with alpha crystallin from the aged lens, alpha crystallin from the newborn lens was much more effective in the inhibition of beta L crystallin denaturation and precipitation induced in vitro by heat. Together, these results demonstrate that during the aging process, the alpha crystallins lose their ability to protect against protein denaturation, consistent with the hypothesis that the alpha crystallins play an important role in the maintenance of protein native structure in the intact lens. PMID- 1424727 TI - The effect of chlorpromazine on endotoxin-induced uveitis in the Lewis rat. AB - Chlorpromazine (CPZ) has been used extensively in the treatment of psychiatric disorders, and has recently been shown to possess systemic anti-inflammatory properties as well. To investigate the potential effects of CPZ on ocular inflammation, we evaluated its action on endotoxin-induced uveitis (EIU) in Lewis rats. At three different dosage levels, CPZ produced highly significant reductions in the mean aqueous aspirate inflammatory cell counts and histological inflammatory scores as compared to controls treated with vehicle only. Analysis of aqueous fluid demonstrated a similar decrease in protein concentration and phospholipase A2 (PLA-2) activity in the treated animals. The ability of CPZ to inhibit the development of EIU may be related to its properties as a calcium channel blocker and inhibitor of the enzyme phospholipase A2. PMID- 1424726 TI - Glycation of lens membrane intrinsic proteins. AB - Changes occurring at the membrane are believed to be the decisive factors in the initiation of diabetic cataract. During diabetic hyperglycemia lens crystallins were shown to undergo glycation. Several studies indicated that glycation brings about protein conformational changes thus implicated in cataractogenesis. Since the membrane proteins are the first targets for glycation, in this study we measured the glycation of alkali washed urea-insoluble membrane proteins from control and diabetic rats by two different methods, phenyl-boronate affinity chromatography and [3H]NaBH4 reduction, and confirmed by amino acid analysis. There was a significant increase in the glycation of membrane proteins in diabetic cataract lenses when compared to controls. It appears that lysine is the major site of glycation. Concomitant to early glycation, there was an increase in non-tryptophan fluorescence (Ex: 350 nm/Em: 440 nm) in the diabetic lens membrane proteins suggesting the presence of advanced glycation mediated protein cross links. In order to identify whether the major membrane intrinsic protein, MIP26, undergoes glycation, we isolated MIP26 along with its degradatory product MIP22 as one peak on molecular sieve HPLC. HPLC isolated MIP26/MIP22 was further separated on SDS-PAGE followed by slicing and counting. This analysis revealed that MIP26 and MIP22 were more or less equally glycated in controls, however, in diabetic rats glycation of MIP22 was glycated slightly higher than MIP26. Moreover, the proportion of MIP22 increased by about 2-fold in diabetic lenses compared to controls. Thus it appears that major glycation sites are still retained in MIP22 in diabetic rat lenses. In vitro glycation studies with bovine lens membranes were also done using 14C glucose, followed by SDS-PAGE and autoradiography. The major protein glycated in vitro also seems to be MIP26. Interestingly, MIP22 was less glycated than MIP26 in vitro. PMID- 1424728 TI - Collagenolytic/gelatinolytic metalloproteinases in normal and keratoconus corneas. AB - Cells of keratoconus corneas have been reported to produce higher levels of collagenolytic/gelatinolytic enzymatic activities than do cells of normal corneas. The current study investigates the contribution of 1) specific enzyme gene products, and 2) the degree to which these proteins are present in the activated forms, to the increased enzymatic activities. We demonstrate that two neutral gelatinolytic enzymes, a 66/59 kD form and a 92 kD form, can be directly extracted from both normal and keratoconus corneas. These enzymes are identified as the pro- and activated forms of MMP-2 and as the pro-form of MMP-9, specific members of the matrix metalloproteinase family. Normal and keratoconus corneas show no significant differences in amounts or types of extractable neutral gelatinases, nor in the amounts or types that they synthesize in culture. Furthermore, in both the normal and keratoconus corneas, gelatinases are found primarily in the inactive form. These studies suggest the possible importance of changes in proteinase inhibitor levels to the characteristic biochemical features of keratoconus corneas. PMID- 1424729 TI - The retinal pigment epithelium induces fenestration of endothelial cells in vivo. AB - Rodent photoreceptor dystrophies are characterized by late stage ingrowth of retinal blood vessels into the retinal pigment epithelium (RPE) where they proliferate. Some of these vessels develop the fenestrated phenotype of the choriocapillaris (CC). To determine if development of fenestrae in these endothelial cells is a function of the duration of time the endothelial cell had been encapsulated by the RPE, we did an ultrastructural morphometric study of these vessels in urethane induced photoreceptor degeneration in Long-Evans rats. Retinas of animals aged 20, 24, 40 and 56 weeks were studied. The fraction of vessel profiles within the RPE that had fenestrated endothelial cells increased from 10% to 90% between 20 to 56 weeks. The average number of fenestrae per vessel increased approximately 25 fold between 20 and 24 weeks but stabilized after that, despite a decrease in the number of vessels present at 56 weeks. A large number of degenerated retinal vessel profiles were seen in the RPE at 40 weeks. These facts support the idea that the presence of the RPE induces endothelial cell fenestrae, and also show that a complex process of remodelling including proliferation and degeneration is occurring in these vessels. Analogies between the basic cell biology of neovascularization occurring in these rodent models and that of proliferative diabetic retinopathy and age-related macular degeneration are discussed. PMID- 1424730 TI - Retinyl ester hydrolysis in the rabbit lacrimal gland. AB - The lacrimal gland stores retinyl esters which are synthesized by the enzyme acyl CoA:retinyl acyl transferase. Retinol is released from retinyl ester reserves by retinyl ester hydrolase (REH). Since the lacrimal gland secretes retinol, this gland should also contain this enzyme. To identify bile salt-dependent REH activity, rabbit lacrimal glands were homogenized in 0.05 M Trismaleate buffer, and enzyme activity was determined in the tissue homogenate, in the membrane fraction and in the cytosolic fraction by measurement of production of retinol from retinyl palmitate (nmol retinol produced/mg protein/h). In the lacrimal gland, production of retinol was optimal in the presence of 200 mM CHAPS at pH 7. The REH activity in the presence of 1000 microM retinyl palmitate was 2.38 +/- 0.18 nmol/mg/h in the homogenate, 1.13 +/- 0.16/nmol/mg/h in membranes and 3.25 +/- 0.26 nmol/mg/h in cytosol. By comparison, REH activity in rabbit liver was 6.58 +/- 0.75 nmol/mg/h. The REH activity in lacrimal gland was not affected by vitamin A deficiency. These data are consistent with the presence of retinyl ester hydrolase activity in the lacrimal gland and provide further evidence that this gland is adapted for metabolism and secretion of retinol. PMID- 1424731 TI - The 53kDa polypeptide component of the bovine fibre cell cytoskeleton is derived from the 115kDa beaded filament protein: evidence for a fibre cell specific intermediate filament protein. AB - The 115kDa protein found enriched in the PMCC (plasma membrane-cytoskeleton complex) fraction of the cortex in bovine lens fibre cells is proteolytically processed to a stable 53kDa product. The 115 kDa protein and the 53kDa polypeptide have been purified by a combination of ion exchange and hydroxyapatite chromatography. Tryptic peptide mapping using reverse phase HPLC and subsequent peptide sequencing confirmed that the 53kDa polypeptide is derived from the 115kDa protein. The 53kDa fragment is also a component of the PMCC as well as being a major component of the urea soluble fraction of lens plasma membranes which have been extracted with buffers containing 1M KC1. The 53kDa polypeptide has escaped identification as a breakdown product of the 115kDa protein because it is not recognised by a commonly used monoclonal antibody, R2D2, specific for the bovine 115kDa protein. This result suggests that proteolysis is important in determining the function(s) of the 115kDa protein, and that part of this function is satisfied by the 53kDa protein core. Both the purified 115kDa protein and the 53kDa polypeptide were unable to form either beaded or intermediate filaments on their own but they were able to form short 10nm rods indicative of an intermediate stage in intermediate filament assembly. Comparison ot the assembly properties of the 53 and 115kDa proteins indicate that there are sequences in the 115kDa protein which inhibit in vitro assembly. This is similar to the situation with neurofilament proteins. We suggest that the 115kDa protein is a lens-specific intermediate filament protein. PMID- 1424732 TI - Cell-specific expression of LBP-32 mRNA in retina and other locations of newborn mouse eye as revealed by in situ hybridization. AB - LBP-32 is a cell surface and cytoplasmic protein which is thought to both mediate cell attachment to laminin and play a role in translation initiation. In the present study, antisense RNA for LBP-32 was used to document its cellular mRNA expression pattern in newborn mouse eye. In situ hybridization revealed that LBP 32 was distributed uniformly through the retina as well as over anterior oblique muscle, in corneal and lens epithelial cells and in capillary endothelial cells of the choroid. This unique cell-specific expression raises interesting questions of the role of LBP-32 in eye development. PMID- 1424733 TI - Binding of actin to lens alpha crystallins. AB - Actin has been coupled to a cyanogen bromide-activated Sepharose 4B column, then tested for binding to alpha, beta, and gamma crystallin preparations from the bovine lens. Alpha, but not beta or gamma, crystallins bound to the actin affinity column in a time dependent and saturable manner. Subfractionation of the alpha crystallin preparation into the alpha-A and alpha-B species, followed by incubation with the affinity column, demonstrated that both species bound approximately the same. Together, these studies demonstrate a specific and saturable binding of lens alpha-A and alpha-B with actin. PMID- 1424734 TI - The epidemiology and genetics of endogenous uveitis: a review. AB - Epidemiology is frequently neglected in the study of uveitis. Little is known on the incidence and prevalence of this disease. This review presents data on the subject from the literature and from the uveitis clinic at Rotterdam. The distribution of uveitis varies in different parts of the world and these differences might be attributed to geographic, alimentary or genetic factors. The discovery of associations of certain types of uveitis and HLA antigen subclasses provided at least part of an explanation for racial and genetic factors. These associations are dealt with in more detail. PMID- 1424735 TI - Adoptive transfer of experimental autoimmune uveoretinitis in HgCl2 injected rats. AB - We previously demonstrated that mercuric chloride (HgCl2) injected-(Lewis x Brown Norway) F1 rats are protected against experimental autoimmune uveoretinitis (EAU) induced by active immunization with the retinal S-antigen (S-Ag). To better understand the mechanisms of the protection promoted by HgCl2, we studied the effect of HgCl2-induced autoimmune disease on transferred EAU. We demonstrate herein that HgCl2 has no effect on adoptively transferred EAU. Therefore, the HgCl2-induced autoimmune disease does not affect effector S-Ag specific T cells activated in vitro but acts at an earlier stage. PMID- 1424736 TI - Induction of experimental autoimmune uveitis by the retinal photoreceptor cell protein, phosducin. AB - Experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are CD4+ T cell mediated inflammatory diseases of the retina and uveal tract of the eye and the pineal gland respectively. They can be induced in experimental animals by immunization with several well characterized retinal autoantigens. We induced a mild to moderate EAU and EAP in Lewis rats by immunization with phosducin, a 33K retinal phosphoprotein which is involved in the phototransduction of vision. In contrast to the severe EAU induced by other retinal antigens like S-antigen (SAg) or interstitial retinoid binding protein (IRBP), the clinical disease was late in onset, low grade in severity and predominantly affected the posterior segment of the eye. Our study demonstrates that another photoreceptor cell protein, phosducin, is capable of eliciting EAU and EAP. PMID- 1424737 TI - Pathogenicity and immunogenicity of recombinant human retinal S-antigen fusion protein. AB - A full-length cDNA clone to human S-antigen (HS-ag) was isolated from lambda gt 10 human retinal library and expressed as a fusion protein with glutathione S transferase (GST) in E. Coli. Uveitogenicity and immunogenicity of recombinant GST-HS-ag fusion protein and native HS-ag were compared in EAU-susceptible Lewis rats. Recombinant HS-ag was found less uveitogenic than native HS-ag. Animals inoculated with recombinant HS-ag developed EAU on day 17, three days later than those inoculated with native HS-ag, the incidence of the disease was reduced from 80% to 58% and the score of clinical severity reduced from 2.2 to 1.3 points respectively. In contrast, rGST-HS-ag was more immunogenic than native HS-ag as it elicited four times higher levels of antibodies which reacted specifically with both antigens. PMID- 1424738 TI - Interphotoreceptor retinoid binding protein induced experimental autoimmune uveitis: an immunophenotypic analysis using alkaline phosphatase anti-alkaline phosphatase staining, dual immunofluorescence and confocal microscopy. AB - Using a Lewis rat model of IRBP induced EAU, we have examined the progress of leucocytes infiltrating the uveitic eye. APAAP and dual immunofluorescence were used to show that ED7 and 8 (CD11b/CD18) positive monocytes, W3/25 and OX8 (CD4 and CD8) lymphocytes were prominent in the initial inflammatory exudate around the retinal vessels and in the choroid. ED1 positive monocytes were also observed in the choroid. As disease progressed, these cells moved into the inner retina, vitreous and ROS. ED8 positive cells were the first to appear in the ROS. This was followed by the later appearance of ED2 tissue macrophages in the vitreous and ED3 inflammatory macrophages in the vitreous and ROS. PMID- 1424739 TI - Suppression of experimental autoimmune uveoretinitis by prazosin, an alpha 1 adrenergic receptor antagonist. AB - S-antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU) was suppressed in Lewis and PVG rats by treatment beginning 4 days post immunization with prazosin, a specific alpha 1-adrenergic receptor antagonist. A significant suppression of EAU was observed at clinical and histological levels in both treated groups compared to a severe EAU which developed in controls. Fluorescein angiography showed no leakage of dye from the optic disc of a treated PVG rat presenting no ocular inflammation by clinical examination. The treatment had no effect on the titer of anti-S-Ag antibodies. Perivascular infiltrates of T lymphocytes and macrophages together with alterations of blood-retinal barrier permeability are early events in EAU. Prazosin, by acting on the vascular alpha 1 adrenoreceptors, inhibits vasospasm, preserves blood-retinal-barrier integrity and prevents vascular edema and early inflammatory cell infiltration observed in EAU. PMID- 1424740 TI - Pinealitis coincident with recurrent uveitis: immunohistochemical studies. AB - Although experimental models of autoimmune uveitis predict pinealitis coincident with uveitis, there is no direct evidence of pineal pathology accompanying a human uveitis. Horses with naturally occurring uveitis are a potential source of eye and pineal tissues that are not available from human patients with active uveitis. We have observed pinealitis in a mare with equine recurrent uveitis. By immunohistochemistry we demonstrated immunoglobulin and MHC Class II antigen on infiltrating and resident cells of eye and pineal gland. These results support the relevance of the animal models and suggest that pinealitis may be coincident with some human uveitides. PMID- 1424741 TI - Adhesion molecules are expressed in the human retina and choroid. AB - Immunoperoxidase staining of samples of normal human retina and choroid was performed to demonstrate selected adhesion molecules in vivo. Intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-3 (LFA-3) and endothelial leucocyte adhesion molecule-1 (ELAM-1) were expressed on retinal vascular endothelium and ICAM-1 and ELAM-1 in the region of the external limiting membrane. The very late antigen-2 (VLA-2) was found around the retinal ganglion cells and in the inner and outer fibre layers. The endothelium on the choriocapillaris showed moderate staining of ICAM-1, and slight staining of LFA-3 and ELAM-1. The presence of these molecules in this distribution strongly suggests they have an important role in the pathogenesis of immunologically mediated ocular conditions. PMID- 1424742 TI - Production of interleukin-6 by human retinal pigment epithelium in vitro and its regulation by other cytokines. AB - Interleukin-6 (IL-6) is a pleiotropic cytokine which produces uveitis if administered intraocularly. It has been demonstrated in the aqueous of patients with various uveitis entities. We have investigated the ability of human retinal pigment epithelium (RPE) to produce IL-6 in vitro, both unstimulated, and in the presence of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF), interferon (IFN) gamma, and lipopolysaccharide (LPS). Five human RPE cell lines were cultured over a 6-day period, both unstimulated and in the presence of these cyokines. IL-6 in the supernatants was measured using an ELISA assay. Unstimulated RPE produced small amounts of IL-6. IL-1 at 100 or 10 U/ml markedly upregulated IL-6 production, and TNF at 1000, 100 or 10 U/ml did so to a lesser extent. Neither IFN gamma or LPS alone increased IL-6 expression, but together gave significant upregulation. Thus human RPE can produce IL-6 and may be the source of this cytokine in ocular inflammatory states. PMID- 1424743 TI - Analysis of IL-6 levels in human vitreous fluid obtained from uveitis patients, patients with proliferative intraocular disorders and eye bank eyes. AB - Several studies suggest a role for IL-6 in the pathogenesis of uveitis. Earlier we have shown that aqueous humour obtained from patients with uveitis contained raised levels of IL-6. In the study described here we investigated the IL-6 levels in vitreous fluid samples obtained from 75 uveitis patients with different uveitis entities. Vitreous samples from 14 patients with proliferative intraocular disorders (PID) and 29 eye bank eyes were used as controls. All the samples were tested in the IL-6 B9 bioassay as well as in a sensitive ELISA for IL-6. Raised IL-6 levels were detected in the vitreous fluid of uveitis patients as well as patients with PID, implicating IL-6 as a common inflammatory mediator. The highest mean level of IL-6 was found in the vitreous fluid of patients with acute retinal necrosis. The mean IL-6 levels measured by the ELISA were higher compared to the levels measured by the B9 bioassay. This may be caused by the presence of B9 bioassay inhibitory factors in the vitreous fluid of these patients. PMID- 1424744 TI - Cytokines in human intraocular inflammation. AB - The presence of interleukin 6 (IL-6), interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor (TNF) was investigated in vitreous and aqueous aspirates from eyes undergoing vitrectomy for the treatment of different inflammatory conditions. Cadaveric vitreous from 10 normal subjects were used as controls. IL-6 was observed in 5 specimens from eyes with idiopathic uveitis (range = 26-264 pg/ml), in 2 specimens from eyes with uveitis complicated with retinal detachment (28 and 279 pg/ml, respectively), in 6 samples from eyes with diabetic retinopathy (range = 5-480 pg/ml), in one sample from an eye with phacolytic glaucoma (1190 pg/ml) and in one specimen from an eye with Behcet's disease (366 pg/ml). Although IL-1 was detected in 80% of all the samples investigated, concentrations of this cytokine greater than 3 pg/ml were only observed in 2 specimens from eyes with uveitis (5 and 20 pg/ml, respectively) and 2 samples from eyes with diabetic retinopathy (3 and 31 pg/ml, respectively). TNF was present in 3 specimens from eyes with uveitis (range = 2-24 pg/ml) and 1 sample from eyes with diabetic retinopathy (4 pg/ml), but was not detected in the eyes with phacolytic glaucoma or Behcet's disease. IL-2 (less than 0.1 U/ml) was detected in one sample from an eye with uveitis, one specimen from an eye with uveitis complicated with retinal detachment and 2 samples from eyes with diabetic retinopathy. None of the cytokines measured were detected in any of the control vitreous. The present observations suggest that cytokines, particularly IL-6 and IL-1, may act as local amplification signals in pathological processes associated with chronic eye inflammation. PMID- 1424745 TI - Soluble interleukin-2 receptors in retinal vasculitis. AB - Soluble interleukin-2 receptor (sIL-2R) levels were measured in the serum of 27 patients with retinal vasculitis, 16 with vasculitis purely isolated to the eye (RV) and 11 with vasculitis associated with a systemic inflammatory disease (RV+SID). Levels of sIL-2R were statistically significantly increased (mu 986, SD 845 U/ml, p = 0.013) only in the RV+SID group as compared to healthy controls. The highest levels being found in patients with sarcoidosis (mu 1436, SD 1083 U/ml). There was no correlation with disease activity or with systemic corticosteroid therapy. Serum sIL-2R measurements appear to be of limited use in the management of patients with retinal vasculitis, but may be of value in those patients with sarcoidosis. Longitudinal measurements with larger numbers of patients are required to confirm this. Serum sIL-2R levels were also statistically significantly increased (mu 843, SD 171 U/ml, p less than 0.0001) in 21 patients with Fuchs' heterochromic cyclitis. As this is a chronic condition with mild inflammatory activity and no associated systemic disease, the explanation for this finding is unknown. PMID- 1424746 TI - Anti-endothelial cell antibodies in retinal vasculitis. AB - Auto-antibodies to endothelial cells are found in a variety of vasculitic disorders including two diseases associated with retinal vasculitis: Behcet's disease and multiple sclerosis. In this study we have examined the prevalence of anti-endothelial cell antibodies [AECA] in 15 patients with retinal vasculitis [RV] associated with Behcet's disease, multiple sclerosis or sarcoidosis and 20 patients with idiopathic retinal vasculitis. 47% of patients with RV associated with systemic disease and 35% of patients with idiopathic RV had AECA, compared to 1% of 70 normal controls. The mean levels of AECA were similar in both groups of patients, and comparable to levels found in other systemic vasculitides. PMID- 1424747 TI - Anticardiolipin antibodies in uveitis. AB - Anticardiolipin antibodies (ACA) have been described in association with thrombosis and several vascular diseases and may be involved in retinal vasculitis. To investigate this question we tested sera from 86 patients with posterior uveitis and 100 healthy controls for the presence of anticardiolipin antibodies. The antibody was present in 15 patients: in 7 of the patients with acute retinal necrosis (n = 24), in 4 with idiopathic retinal vasculitis (n = 10), 3 with syphilis (n = 6) and in one SLE patient with retinal vasculitis. Ten patients had IgA-type anticardiolipin antibodies, 6 had IgM-type and 4 had IgG type anticardiolipin antibodies. Anticardiolipin antibodies could not be detected in sera from uveitis patients with Behcet's disease (n = 10), sarcoid (n = 9), toxoplasmosis (n = 7), multiple sclerosis (n = 3) or Birdshot chorioretinopathy (n = 10). Ten of the healthy controls had cardiolipin antibodies of the IgM class. The exact role of these auto-antibodies in the pathogenesis of retinal vasculitis remains to be resolved. PMID- 1424748 TI - The use of lithium clearance studies in the early detection of cyclosporin A (CsA) nephrotoxicity: a protocol of renal function assessment with CsA therapy. AB - Cyclosporin A nephrotoxicity was studied with the use of lithium and creatinine clearance tests in 18 patients with chronic intraocular inflammation (duration of treatment 3-48 months). In 11 patients lithium clearance and fractional excretion of lithium were significantly reduced (compared with pretreatment levels) within the first six months of treatment. There was no significant change in either serum creatinine or creatinine clearance within this period. In 14/18 patients there was a significant reduction in lithium clearance and fractional excretion of lithium during the treatment period. 7 patients whose therapy was stopped because of continuing nephrotoxicity despite dose reduction, demonstrated some reversibility of renal function on cessation of cyclosporin A. We propose a protocol for the assessment of renal function in these patients so that with dose modulation the changes in these parameters can be minimised, reducing the risk of renal impairment, whilst maximising immunosuppressive treatment. PMID- 1424749 TI - The blood-retinal barrier in experimental autoimmune uveoretinitis (EAU): a review. AB - The blood-retinal barrier (BRB) is believed to play an important part in the pathogenesis of experimental autoimmune uveoretinitis (EAU). Central to the disease process is the recruitment of inflammatory cells from the circulation, a mechanism that is controlled in part by the BRB. As the disease progresses the BRB becomes disrupted first to small and then to large molecular weight tracers. In these two respects EAU shares many similarities with experimental autoimmune encephalomyelitis (EAE) in which there is dysfunction of the blood-brain barrier (BBB). In EAU, however, the differential roles played by the two barrier sites that comprise the BRB are not clear although some evidence would suggest that it is the retinal endothelium that is initially involved. BRB breakdown in EAU has been found to occur concomitantly with lymphocyte infiltration by mechanisms that remain to be elucidated. PMID- 1424750 TI - Eye-derived cytokines and the immunosuppressive intraocular microenvironment: a review. AB - The normal aqueous humor contains a variety of soluble immunosuppressive factors, including transforming growth factor-beta, alpha-melanocyte stimulating hormone, and vasoactive intestinal peptide. These factors are largely the secretory products of parenchymal cells of the iris and ciliary body. TGF beta has recently been shown to alter the functional capacity of intraocular antigen presenting cells, such that they are capable of inducing Anterior Chamber Associated Immune Deviation (ACAID). This deviant systemic immune response is characterized by an impaired capacity to mount an effective cell-mediated immune attack directed at antigens that are placed in, or arise within, the eye. A second property of immunosuppressive factors in aqueous humor is to suppress directly the expression of delayed hypersensitivity in the anterior chamber. In fact, even when the intraocular microenvironment is disturbed by local instillation of gamma interferon, making it possible for limited expression of cell-mediated immunity in the eye, the microenvironment of the anterior chamber remains profoundly immunosuppressive. In this latter instance, prostaglandins replace TGF beta as the major molecular mediators of suppression in the aqueous humor. In the aggregate, factors present in the normal (or perturbed) intraocular microenvironment have the capacity to modify both the afferent and efferent limbs of the systemic immune response, and this accounts for the longstanding observation that the anterior chamber is an immunologically privileged site. Since evidence suggests that the eye can mobilize more than one molecular mechanism in its effort to limit the sight-destroying potential of immunogenic inflammation, we believe that elucidation of intraocular cytokines and factors that create and maintain an immunosuppressive microenvironment will contribute to a better understanding of the pathogenesis of the acute and chronic uveitides, especially those of autoimmune and infectious etiology. PMID- 1424751 TI - Antigen processing and presentation in the eye: a review. AB - The recognition event between self-antigen, the MHC and the T cell receptor has become the target for potential immunotherapy of T cell mediated autoimmune disease. For this approach to succeed in uveoretinitis, uniformity in T cell receptor usage, restricted MHC usage and limited epitope recognition by individuals would be required. In this study we have shown that despite clonal heterogeneity of response to multideterminate retinal extract antigens, proliferation to the antigens tested was restricted by the IA MHC class II molecule. Different patterns of reactivity to retinal antigens in the presence of various protease inhibitors was observed. Natural processing of IRBP appears to be complex, requiring a number of enzymes to generate immunogenic fragments, in contrast, for S-antigen, plasmin alone may suffice. The RPE cells which are potential processors and presenters of retinal antigens produce PGE2 and may act as suppressors of ocular inflammation. PMID- 1424752 TI - Epitopes and idiotypes in experimental autoimmune uveitis: a review. AB - Retinal S-antigen (SAg) and interphotoreceptor retinol-binding protein (IRBP) induced experimental autoimmune uveitis (EAU) and experimental autoimmune pinealitis (EAP) are good models for studying the mechanisms involved in autoimmune diseases. Many immunogenetically active epitopes have been identified in these proteins but immunodominance of one or more epitopes in vivo, has not yet been established. In this paper we present and discuss some experiments that led to the discovery of a dominant "tolerogenic" epitope in SAg. We also demonstrate the presence of cross reactive epitopes in the two potent retinal antigens, SAg and IRBP and finally introduce early data on a unique anti S2.4.c5 idiotypic (Id) monoclonal antibody (MAb) which appears to be a site non associated antibody that binds not only to s2.4.c5 but also to SAg. PMID- 1424753 TI - Macrophages in experimental autoimmune diseases in the rat: a review. AB - In the pathogenesis of most experimental autoimmune diseases T lymphocytes play a crucial role in the initiation, whereas macrophages are essential in the effector phase. This review deals with several methods to elucidate the exact role macrophages play in different stages of autoimmune models in the rat. By using monoclonal antibodies an inventory has been made on the different macrophage subsets that are present in the infiltrates of the affected tissues. That macrophages play a decisive role in provoking the clinical signs has been shown by several macrophage elimination studies. The severe tissue damage caused by macrophages is brought about by the release of inflammatory mediators. Especially interference with the production or action of these products could provide new therapeutical means. PMID- 1424755 TI - Use of ACAID to suppress interphotoreceptor retinoid binding protein-induced experimental autoimmune uveitis. AB - Experimental Autoimmune Uveitis (EAU) was induced by immunization with bovine interphotoreceptor retinoid binding protein (IRBP) in B10.A mice. The experiments were performed to evaluate whether Anterior Chamber Associated Immune Deviation (ACAID) can be induced by IRBP when injected intracamerally. The results indicate that anterior chamber (AC) injection of IRBP impaired the development of IRBP specific delayed hypersensitivity and prevented the expression of EAU following immunization with IRBP-CFA. Adoptive transfer of spleen cells obtained from mice that received IRBP into AC suppressed EAU, whether administered prior to or after the uveitogenic regimen. Most important, IRBP-specific suppressor cells from AC IRBP treated mice when injected into IRBP-EAU mice suppressed and eliminated already established intraocular inflammation. IRBP-specific, ACAID-inducing suppressor T cells act on the efferent limb of the immune response, and represent ideal modalities for treating already established EAU. PMID- 1424754 TI - Genetic factors in susceptibility and resistance to experimental autoimmune uveoretinitis. AB - Experimental autoimmune uveoretinitis (EAU) can be induced in susceptible stains of rats and mice by immunization with purified retinal antigens, and serves as a model for human uveitis. Because strong HLA associations have been noted in a number of human uveitic diseases, we investigated the role of major histocompatibility complex (MHC) vs. non-MHC genes in the control of susceptibility to ocular autoimmunity, using the mouse and the rat EAU models. It was shown that EAU expression in mice requires both a susceptible MHC haplotype and a "permissive" genetic background. MHC control of susceptibility was tentatively mapped to the I-A subregion in H-2k. I-Ek expression appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine "permissiveness" or "nonpermissiveness" of a particular genetic background, as studied in mice and rats, may include diverse genetic mechanisms spanning regulation of cytokines, hormones, vascular effects and the T cell repertoire. Taken together, the data suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background. PMID- 1424756 TI - Recent progress in the use of intravenous immunoglobulin. PMID- 1424757 TI - Retinopathy of prematurity. AB - ROP is a common disorder among extremely low-birth-weight premature infant survivors and may cause total vision loss in as many as 2% to 4% of those weighing less than 2 lb (1 kg) at birth. Regular examinations begun in the intensive care unit permit early detection and treatment of progressive ROP, reducing visual impairment. Ongoing research into antioxidants, angiogenesis, light exposure, and newer surgical techniques may offer new approaches for preventing and treating established ROP. Infants who have had ROP that regressed should continue regular ophthalmologic follow-up to detect and treat myopia, strabismus, and if they have cicatricial sequelae, late retinal detachments as teens or adults. Infants who develop retinal detachments should be referred for early intervention and special education programs and remain in regular ophthalmologic follow-up for the detection and treatment of further ophthalmic complications. PMID- 1424759 TI - Coronary artery bypass surgery. PMID- 1424758 TI - Lumbosacral spine imaging: physioanatomic method. AB - Noninvasive evaluation of low back and leg pain has progressed rapidly over the past decade. The development of computed tomography, single-photon emission computed tomographic bone scan, and magnetic resonance imaging has markedly increased diagnostic accuracy in detecting pathologic conditions. With this increased accuracy has come recognition of a 50% prevalence of underlying abnormalities in patients between 20 and 60 years old who have no symptoms. When such patients have a back injury, subsequent imaging will show in half of the population studied abnormalities that are not related to an acute injury. Degeneration of the spine progresses in all patients throughout their lifetime, and nearly all of the population will have back discomfort at some time. Political- and judicial-based compensation for back injuries related to accidents and on-the-job injuries provides an incentive for patients not to improve on therapy and to exaggerate symptoms, further complicating the clinical evaluation of their condition. The goal of physioanatomic noninvasive and invasive imaging evaluation presented in the following chapters is to increase specificity by differentiating pain generators from asymptomatic underlying pathologic conditions. When used with intensive conservative management and psychologic testing, this physioanatomic approach has resulted in much better treatment outcomes in our experience. The physioanatomic approach is quite simple, consisting of rigorous correlation of pathologic changes demonstrated by noninvasive imaging modalities (computed tomography, single-photon emission computed tomographic bone scan, and magnetic resonance), or invasive modalities (diskography-enhanced computed tomography, nerve root block and facet block) with the patient's symptoms to evaluate whether the symptoms and the pathologic lesion are concordant or discordant. Patient symptoms and history are evaluated by use of a pain drawing and information sheet. The patient's pain pattern is categorized into a nonspecific pattern or into one of four recognizable pathway patterns (radicular, dorsal ramus, polyneuropathy, and sympathetic). Because each spinal lesion is typically manifested primarily via one of the four symptom pathways, the distribution of expected symptoms from each pathologic feature can be compared with the patient's pain drawing, and an assessment of the significance of imaged lesions can be made. The patient's presenting symptoms are also used to determine the most cost-effective and efficacious use of initial diagnostic imaging evaluation. In a minority of patients the findings on noninvasive imaging either will not correlate with the patient's symptoms or will demonstrate multiple abnormalities that could account for the patient's symptoms. In these patients, invasive techniques are extremely helpful in defining a pain generator or pain generators.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1424760 TI - The biology and practice of surgical drains. Part II. PMID- 1424761 TI - Determination to flower in Nicotiana. PMID- 1424762 TI - Role of cell rearrangement in axial morphogenesis. PMID- 1424763 TI - Mechanisms underlying the development of pattern in marsupial embryos. PMID- 1424764 TI - Experimental chimeras: current concepts and controversies in normal development and pathogenesis. PMID- 1424766 TI - Transcription factors and mammalian development. PMID- 1424765 TI - Genetic analysis of cell division in Drosophila. PMID- 1424767 TI - Cellular basis of amphibian gastrulation. PMID- 1424769 TI - Membrane defenses against attack by complement and perforins. PMID- 1424768 TI - Role of the extracellular matrix in amphibian gastrulation. PMID- 1424770 TI - Regulation of complement by membrane proteins: an overview. PMID- 1424771 TI - Effects of the membrane attack complex of complement on nucleated cells. PMID- 1424772 TI - Glycosyl-phosphatidylinositol anchoring of membrane proteins. PMID- 1424773 TI - Paroxysmal nocturnal hemoglobinuria. PMID- 1424774 TI - Perforin: structure, function, and regulation. PMID- 1424775 TI - Complement receptor type 1. PMID- 1424776 TI - Membrane cofactor protein. AB - MCP serves to down-regulate the activation of complement on host tissue. It performs this function by serving as a cofactor for the factor I-mediated cleavage of C3b and C4b. MCP is most likely an intrinsic regulator, i.e., it primarily protects its home cell. The wide tissue distribution of MCP mirrors this critical function of host cell protection. With the exception of erythrocytes, every cell and tissue examined expresses this protein. MCP is represented as two broad heterogeneous bands on SDS-PAGE with M(r)s of 51,000 58,000 and 59,000-68,000. The quantity of each form expressed is inherited in an autosomal codominant fashion. In most cells and cell lines, four isoforms of MCP predominate and arise by alternative splicing of a single MCP gene. All forms possess four repeating modules of--60 aminoacids, an area enriched in serines, threonines, and prolines [(STP), probable site of O-linked glycosylation], a short area of unknown function, a transmembrane domain, and a cytoplasmic tail. The isoforms differ, however, in the length and composition of the STP region and in the cytoplasmic tail. Alternative splicing of a single exon within the STP region determines the protein phenotype. Alternative splicing at the COOH_terminus gives rise to two distinct cytoplasmic tails. The biological significance of these structural variations in the STP and cytoplasmic tail regions is being investigated. PMID- 1424777 TI - Homologous restriction factor. PMID- 1424778 TI - Antigen markers of macrophage differentiation in murine tissues. PMID- 1424779 TI - The biology of CSF-1 and its receptor. PMID- 1424780 TI - The role of myristoylated protein kinase C substrates in intracellular signaling pathways in macrophages. PMID- 1424781 TI - Ribosomal RNA metabolism in macrophages. PMID- 1424782 TI - Mononuclear phagocytes as targets, tissue reservoirs, and immunoregulatory cells in human immunodeficiency virus disease. AB - We have presented evidence in this review for the following: 1. Macrophages are likely the first cell infected by HIV. Studies document recovery of HIV into macrophages in the early stages of infection in which virus isolation in T cells is unsuccessful and detectable levels of antibodies against HIV are absent. 2. Macrophages are major tissue reservoirs for HIV during all stages of infection. Unlike the lytic infection of T cells, many HIV-infected macrophages show little or no virus-induced cytopathic effects. HIV-infected macrophages persist in tissue for extended periods of time (months) with large numbers of infectious particles contained within intracytoplasmic vacuoles. 3. Macrophages are a vector for the spread of infection to different tissues within the patient and between individuals. Several studies suggest a "Trojan horse" role for HIV-infected macrophages in dissemination of infectious particles. The predominant cell in most bodily fluids (alveolar fluid, colostrum, semen, vaginal secretions) is the macrophage. In semen, for example, the numbers of macrophages exceed those of lymphocytes by more than 20-fold (Wolf and Anderson 1988). 4. Macrophages are major regulatory cells that control the pace and intensity of disease progression in HIV infection. Macrophage secretory products are implicated in the pathogenesis of CNS disease and in control of viral latency in HIV-infected T cells. This litany of events in which macrophages participate in HIV infection in man parallels similar observations in such animal lentivirus infections as visna maedi or caprine arthritis-encephalitis viruses. HIV interacts with monocytes differently than with T cells. Understanding this interaction may more clearly define both the pathogenesis of HIV disease and strategies for therapeutic intervention. PMID- 1424783 TI - Interactions between macrophages and Legionella pneumophila. PMID- 1424784 TI - Chronic granulomatous disease: an update and a paradigm for the use of interferon gamma as adjunct immunotherapy in infectious diseases. PMID- 1424785 TI - Macrophages in the uterus and placenta. PMID- 1424787 TI - The American Academy of Dermatology's Melanoma/Skin Cancer Detection and Prevention Program. PMID- 1424786 TI - Macrophage-derived growth factors. PMID- 1424788 TI - Sunscreen dermatitis: Part II--The cinnamates. PMID- 1424789 TI - A dermatologic diary. Portrait of a practice. PMID- 1424790 TI - Genital psoriasis. AB - Psoriasis of the genitalia occurs in all age groups from infancy to the elderly. Approximately one-quarter to one-half of various epidemiologic studies report that genital psoriasis occurs with a higher frequency in males than in females. Therapeutic modalities for management of psoriasis in this site underscore the need for caution in not irritating the sensitive genital skin. Preventive measures include avoiding tight under- and outer-garments that provoke penile or vulvar psoriasis as well as maintaining cleanliness of the genital area. PMID- 1424791 TI - Majocchi's granuloma. PMID- 1424792 TI - Persistent painful plaque due to a brown recluse spider bite. AB - The bite of the arthropod Loxosceles is known to cause subdermal hemorrhage, dermal-epidermal separation, inflammatory infiltrates, as well as occlusion and necrosis of small arterioles. We report a case of a brown recluse spider bite that presented as a chronic painful skin plaque, with the unusual histologic findings of a cutaneous and deep subcutaneous hyalinizing panniculitis and myonecrosis. PMID- 1424793 TI - Tongue and cheek: oral lesions in pityriasis rosea. AB - Fifty-one consecutive patients with clinical findings and history consistent with pityriasis rosea underwent a complete oral examination to search for any concomitant oral lesions. One case was omitted from the statistical analysis because the results of a rapid plasma reagin test were positive. Of the fifty remaining cases, eight patients (16 percent) were noted to have various oral lesions, all of which were asymptomatic. These findings suggest that the actual incidence of oral lesions in pityriasis rosea may be higher than previously reported. A complete oral examination in a patient presenting with a papulosquamous eruption may be helpful in ascertaining the diagnosis of pityriasis rosea. PMID- 1424794 TI - Fixed drug eruption to Tylenol: report of two cases and review of the literature. AB - Fixed drug eruptions due to Tylenol (paracetamol, acetaminophen) are very rare. The authors report two additional cases and review the literature. PMID- 1424795 TI - Aquagenic urticaria. AB - Aquagenic urticaria is a rare form of physical urticaria characterized by small follicular wheals with an erythematous flare upon exposure to water. We describe typical lesions in a seven-year-old boy with aquagenic urticaria, cholinergic urticaria, and symptomatic dermatographism, who responded to treatment with ultraviolet B and oral antihistamines. PMID- 1424796 TI - Multiple pilomatricomas: report of two cases and review of the association with myotonic dystrophy. AB - Two patients are reported who experienced multiple pilomatricomas beginning in childhood. Although one patient had no evidence of associated diseases, the second patient was diagnosed with myotonic dystrophy subsequent to the onset of the pilomatricomas. Previous reports of multiple pilomatricomas and the association with myotonic dystrophy are reviewed. PMID- 1424797 TI - Cutaneous pleomorphic large cell lymphoma. AB - The case of a primary cutaneous pleomorphic large cell lymphoma occurring in a twenty-one-year-old woman who presented with a blue-reddish nodule on her left cheek of three months' duration is presented. The tumor consisted of pleomorphic blast cells showing high mitotic activity. On immunohistochemical examination, the majority of the tumor cells expressed CD 3 (Leu-4), CD 4 (Leu-3), HLA-DR CD 30 (Ki-1/Ber-H 2), and CD 25 (IL2 receptor). Twenty-two months after excision of the tumor there is no detectable systemic spread of the lymphoma. This case provides further evidence for recent observations that primary cutaneous Ki-1 positive large cell lymphomas without lymph node involvement may have a favorable prognosis after local treatment despite showing histologic pattern of malignancy. PMID- 1424798 TI - Cutaneous nocardiosis associated with insect bites. AB - We report the first case of cutaneous nocardiosis associated with insect bites. The patient received these insect bites while camping a few days before he presented to the emergency room. The patient was a healthy twenty-six-year-old man, who was asplenic as a result of a motor vehicle accident. He presented to the emergency room with fever, multiple insect bites to his left lower extremity with pustules, lymphangitis, and left inguinal adenopathy. He was hospitalized but his condition failed to improve despite treatment with intravenous nafcillin for three days. Wound and blood cultures subsequently grew Nocardia brasiliensis. Treatment with intravenous amikacin (5 mg/kg every eight hours) was instituted along with oral trimethoprim-sulfamethoxazole double strength twice a day. The patient recovered with minimal scarring of the extremity. The amikacin was stopped after seven days and the patient was discharged to receive oral trimethoprim-sulfamethoxazole. This disease should be kept in mind when cutaneous infections do not respond to standard antibiotics, especially in the southwestern United States. PMID- 1424800 TI - Eyewear, cataracts, and periorbital basal cell carcinoma. AB - Ultraviolet exposure is an important risk factor for basal cell carcinoma. Since eyewear may have a photoprotective effect, this study evaluated the use of prescription eyeglasses and sunglasses in patients with periorbital basal cell carcinoma compared with other facial sites. There was no difference in prescription eyewear use between the groups, and only four patients in each group had regularly worn glasses since childhood. There was an increased occurrence of cataracts and cataract surgery in the group of patients with periorbital tumors, which may indicate a greater cumulative ultraviolet exposure to the orbital and periorbital sites in these patients. PMID- 1424799 TI - Salicylate intoxication after use of topical salicylic acid ointment by a patient with psoriasis. AB - The authors describe a therapeutically well managed case of severe salicylate intoxication in a patient with psoriasis who treated himself with 40 percent salicylic ointment applied to approximately 41 percent of his body surface. Nineteen hours after the application of salicylic acid, his blood level of the agent was 6.04 mmol/liter. The patient underwent hemodialysis and was discharged after fourteen days in good general health. PMID- 1424801 TI - Report of the first international workshop on human chromosome 15 mapping. PMID- 1424802 TI - Molecular and cytogenetic characterization of radiation hybrids specific for human chromosome 16. AB - Two hundred and twenty-three radiation hybrids retaining random fragments of human chromosome 16 were isolated during two successive experiments in HAT medium and screened with a total of 38 DNA probes, corresponding to anonymous DNA or gene sequences localized on chromosome 16. The presence of single or multiple human chromosomal fragments in a small subset of these hybrids was determined using in situ hybridization with total human DNA. The results confirm that individual radiation hybrids are often heterogeneous with respect to the retention and distribution of human fragments, as already suggested by their characterization with DNA probes. A number of these 223 radiation hybrids, whose detailed characterization has not been previously reported, represent a resource for the rapid isolation of new DNA markers or coding sequences from specific regions of chromosome 16 where human disease genes are already known to map. PMID- 1424803 TI - Fluorescence in situ mapping of the human nuclear NAD+ ADP-ribosyltransferase gene (ADPRT) and two secondary sites to human chromosomal bands 1q42, 13q34, and 14q24. AB - A 3.5-kb cDNA probe containing the 23 exons from the coding sequence of human nuclear NAD+ ADP-ribosyltransferase (poly [ADP-ribose] polymerase [ADPRT], E.C.2.4.2.30) was used to map the gene and two additional sites by nonisotopic in situ chromosomal hybridization. The previous localization of the structural gene on 1q42 was confirmed. Two other hybridization peaks on 13q34 and 14q24 suggested the presence of ADPRT pseudogenes. PMID- 1424804 TI - Localization of the human GM-CSF receptor beta chain gene (CSF2RB) to chromosome 22q12.2-->q13.1. AB - The gene for the beta-chain of the human GM-CSF receptor (CSF2RB) has been mapped to chromosome 22 by PCR analysis of a series of human x rodent somatic cell hybrids. In situ hybridization to normal human chromosomes and two translocations involving chromosome 22 and the chromosome expressing the rare fragile site FRA22A place the gene in the region 22q12.2-->q13.1, proximal to the fragile site. PMID- 1424805 TI - Regional localization of the gene for clusterin (SP-40,40; gene symbol CLI) to human chromosome 8p12-->p21. AB - The human clusterin (SP-40,40) gene, designated CLI (complement lysis inhibitor) by the Human Gene Nomenclature Committee, has previously been assigned to chromosome 8. In situ hybridization allowed us to map the locus at 8p12-->p21. PMID- 1424806 TI - Localization of the beta A4-crystallin gene (CRYBA4) on human chromosome 22 in the region q11.2-->q13.1. AB - The chromosomal localization of the human gene (CRYBA4) coding for the eye lens protein beta A4-crystallin has been carried out using a nearly full-length cDNA clone encoding bovine beta A4-crystallin. A panel of 21 human-mouse or human hamster hybrid cell lines derived from different parental combinations was characterized with respect to the human chromosomal content and the presence of well established human chromosome-specific markers. These panels were screened for the presence of CRYBA4 using the bovine cDNA clone as a probe. A 100 percent concordance was observed between the presence or absence of the CRYBA4 and human chromosome 22 indicating that the gene resides on this chromosome. By using cell hybrids containing translocated chromosome 22 segments, the localization could be refined to the region 22q11.2-->q13.1. PMID- 1424807 TI - Chromosomal localization of the mouse prealbumin gene (Ttr) by in situ hybridization. AB - Prealbumin is a serum protein which plays an important role in plasma transport of retinol and thyroxine. The accumulation of a variant prealbumin is associated with a hereditary disorder, familial amyloidotic polyneuropathy (FAP). In situ hybridization with a mouse prealbumin gene cDNA probe was carried out in mouse fibroblasts. Analysis of 114 R-banded metaphases showed that 13% of the total grains were located on chromosome 4 and 46% of the grains on this chromosome were in the region C6-D1. Linkage and syntenic group analysis showed that the prealbumin gene (Ttr) is located between two syntenic groups on mouse chromosome 4, which corresponded to two syntenic groups present on human chromosomes 1 and 9. PMID- 1424808 TI - Mapping of repetitive bovine DNA sequences on cattle Y chromosomes. AB - Three male-specific PCR products of the sequences BC1.2, lambda ES6.0, and BRY.1 were used as probes for Southern blot analyses. Each of these probes generated a complex male-specific band pattern, which showed some quantitative variations among bulls. Hybridization patterns obtained with the BC1.2 and lambda ES6.0 PCR products were interrelated. Chromosomal locations of these repeats were determined by hybridizing the tritiated PCR products in situ to male metaphase spreads. The BC1.2 and lambda ES6.0 PCR products hybridized to Yp13-->p12, whereas the BRY.1 PCR product hybridized over the entire Y chromosome. In addition, the BC1.2 and lambda ES6.0 PCR products hybridized to the distal half of the acrocentric Y chromosome of Bos indicus, indicating that the short arm of the B. taurus Y chromosome is homologous with the telomeric end of the B. indicus Y and supporting the notion that the Y chromosomes of these two species differ by a pericentric inversion. PMID- 1424810 TI - Synaptonemal complex analysis of an autosomal trisomy in the horse. AB - Synaptonemal complex analysis by electron microscopy of a trisomy 28 in a male horse demonstrated a trivalent or a bivalent plus a univalent in primary spermatocytes. Two of the chromosomes making up the trivalent were, most often, completely paired with each other and only partially paired or associated with the third one. Half of the spermatocytes analysed demonstrated heterologous pairing or association between the free axis of the trivalent and the sex bivalent. The pairings remained, to a large extent, into diakinesis-metaphase I. In most pachytene cells one autosomal bivalent showed proximal asynapsis and paired often, heterologously, with the trivalent or the sex bivalent. The horse demonstrated azoospermy, which was due, at least in part, to degeneration at both the spermatocyte and spermatid levels. PMID- 1424809 TI - Synaptonemal complex analysis of a three-breakpoint translocation in a subfertile bull. AB - Somatic chromosome analysis of a subfertile Brown Swiss bull demonstrated a three breakpoint translocation involving chromosomes 1, 8, and 9 in G- and R-banded karyotypes. Based on standard bovine chromosome nomenclature, the translocation was defined as t(1;8;9)(q43;q13;q26). Synaptonemal complex analysis of the chromosome aberration by electron microscopy revealed a hexavalent configuration in 52 of 53 pachytene cells. Twenty-seven cells (51%) had a completely paired hexavalent configuration showing distinctly nonhomologous pairings between normal and/or translocated chromosomes involved in the exchanges. Thirteen cells showed a hexavalent configuration with centrally unpaired chromosome segments but with completely paired terminal arms. In 13 cells (including one at zygotene) the translocation chromosomes formed an open hexavalent, and in one cell there were two completely paired trivalents. Thirty-two cells at diakinesis-MI demonstrated 28 configurations, including one large hexavalent. Testicular histology, testis size, and seminal characteristics were normal. PMID- 1424811 TI - Assignment of the rabbit genes for alpha (PHKA) and beta (PHKB) phosphorylase kinase subunits. AB - The chromosomal locations of the rabbit genes for the alpha and beta subunits of phosphorylase kinase (PHKA and PHKB) were determined by in situ hybridization using rabbit cDNA probes. Our results localize PHKA to the X chromosome at the proximal end of the long arm, near the centromere, and PHKB to the same location on chromosome 5. These assignments support previously reported homoeologies of rabbit and human chromosomes. PMID- 1424812 TI - Male meiosis and gametogenesis in wild house mice (Mus musculus domesticus) from a chromosomal hybrid zone; a comparison between "simple" Robertsonian heterozygotes and homozygotes. AB - Wild male house mice Mus musculus domesticus were collected from the hybrid zone between the John o'Groats race (2n = 32) and the standard race (2n = 40) in northern Scotland. Meiosis in both homozygotes (2n = 32, 36, and 40) and single Robertsonian heterozygotes (2n = 33, 35, and 37) was found to be orderly. At prophase/metaphase I in heterozygotes, a trivalent was formed from the metacentric and two homologous acrocentrics. At pachytene, this trivalent usually had a single side arm at the position of the centromeres, as a result of nonhomologous pairing of the acrocentrics. This side arm persisted into diplotene. Generally only a single chiasma was formed between each acrocentric and the metacentric. Anaphase I nondisjunction frequencies were estimated as 1.5% for the homozygotes and 2.7% for the heterozygotes. The extent of germ cell death between the pachytene and round spermatid stages was 18% greater in heterozygotes than in homozygotes. Our results concur with previous studies which indicate that single Robertsonian heterozygotes in wild house mice have near-normal fertility. PMID- 1424813 TI - Chromosome painting using chromosome-specific probes from flow-sorted pig chromosomes. AB - Biotinylated chromosome-specific probes were prepared from flow-sorted pig chromosomes 1, 13, 18, X, and Y using the degenerate oligonucleotide-primed polymerase chain reaction. Probes prepared in this way can be used to confirm the identity of chromosomes in the bivariate pig flow karyotype and in pig x mouse somatic cell hybrids. PMID- 1424814 TI - Magnetic resonance imaging and spectroscopy of the bone marrow in vivo--with special attention to the possibilities for tissue characterization in patients with leukemia. PMID- 1424815 TI - The pupil of the eye in diabetes mellitus, an indicator of autonomic nervous dysfunction. PMID- 1424816 TI - Prognostic factors in Hodgkin's disease. PMID- 1424817 TI - Cardiac function in hospital survivors of acute myocardial infarction. Evaluation by radionuclide ventriculography. PMID- 1424818 TI - C-peptide used in the estimation of islet beta-cell function in diabetes. PMID- 1424819 TI - Prognosis and prognostic factors in adenocarcinoma of the lung. PMID- 1424820 TI - Epidemiology of pain requiring strong analgesics outside hospital in a geographically defined population in Denmark. AB - Based on obligatory notifications from pharmacies to the National Board of Health about prescription of strong analgesics as well as questionnaires to the prescribing doctors, the occurrence and causes of pain requiring strong analgesics outside hospitals were analysed over a period of one month in Denmark in a limited population (480,000), corresponding to nearly 10% of the Danish population. During one month, strong analgesics were prescribed to 0.2 per cent of the population. The commonest acute conditions were back pain (23%) and trauma (17%). The commonest recurrent acute conditions were headache (25%) and angina pectoris (17%). The commonest chronic non-malignant conditions were back pain (29%) and pancreatitis (7%). The commonest malignant conditions were lung cancer (20%) and colorectal cancer (14%). The commonest conditions indicated under the chronic pain syndrome were headache (33%) and back pain (13%). Conditions requiring strong analgesics reflect to some extent the distribution of painful conditions in the general population. PMID- 1424821 TI - Recording of postoperative wound infections in Denmark. Implementation, surgeons attitude, status and recommendations. AB - PURPOSE: To evaluate the state of the surveillance of surgical infections in Denmark. To investigate whether a negative attitude to infection registration on the part of the chief surgeon is correlated to departments with no plans of recording their infections. DESIGN: Questionnaire sent to all surgical and gynaecological departments in Denmark. PLACE: The National Centre for Hospital Hygiene, Statens Seruminstitut, Copenhagen, Spring 1991. MATERIAL: 73 general, 34 orthopaedic, eight thoracic and vascular surgical departments, seven reconstructive, five neurosurgical, and 31 gynaecological departments. VARIABLES: Kind of specialty, attitudes to infection registration, do register, plan to register, no plans to register, type of program, year of start of registration, satisfaction, problems and suggestive improvements. RESULTS: Out of 170 possible units, 65 were already recording their infection rates, 59 had plans to start registration, 34 had no plans to start, five did not state whether they had any plans to start, and seven units did not respond. The units which were recording their infections had a more positive attitude towards surveillance systems. CONCLUSIONS: We found that the Danish public health service had a high degree of concern about infection surveillance without any legislative or other regulative pressures, and the process of implementing surveillance is still ongoing. The adoption of a common minimal data set is recommended in order to make a national and international comparison of infection surveillance data possible. Enlarging the infection control team may result in a better wound infection surveillance in hospitalised patients. More intensive studies are needed to examine how effectively surveillance prevents postoperative infections. PMID- 1424822 TI - Esophageal manometry in the evaluation of esophageal symptoms. PMID- 1424823 TI - Scintigraphic quantification of pharyngeal retention following deglutition. AB - A procedure is described for quantifying the amount of bolus material retained in the pharynx after completion of a swallow, using radionuclide swallow techniques. Data are derived from scintigraphic time-activity curves. The procedure takes into consideration the differential attenuation of radioactivity through various regions in the body, and expresses the result as a percentage of the total radioactivity in the ingested bolus. Illustrative examples are provided for swallows by normal individuals and patients with head and neck cancer. PMID- 1424824 TI - Viscosity measurements of barium sulfate mixtures for use in motility studies of the pharynx and esophagus. AB - Detailed viscosity measurements have been made of barium sulfate mixtures over a wide range of viscosities for use in radiography of the esophagus, stomach, and duodenum. A new methodology was developed for more accurate estimation of viscosity in non-Newtonian fluids in conventional cylinder-type viscometers. As base cases, the variation of viscosity with shear rate was measured for standard commercial mixes of e.z.hd (250% w/v) and a diluted mixture of liquid e.z.paque (40% w/v). These suspensions are strongly shear thinning at low shear rates. Above about 3s-1 the viscosity is nearly constant, but relatively low. To increase the viscosity of the barium sulfate mixture, Knott's strawberry syrup was mixed to different proportions with e.z.hd powder. In this way viscosity was systematically increased to values 130,000 times that of water. For these mixtures the variation of viscosity with temperature, and the change in mixture density with powder-syrup ratio are documented. From least-square fits through the data, simple mathematical formulas are derived for approximate calculation of viscosity as a function of mixture ratio and temperature. These empirical formulas should be useful in the design of "test kits" for systematic study for pharyngeal and esophageal motility, and clinical analysis of motility disorders as they relate to bolus consistency. PMID- 1424825 TI - Esophageal motor disorders in patients evaluated for dysphagia and/or noncardiac chest pain. AB - During the period January, 1983-October, 1990, 429 subjects were referred for functional evaluation of dysphagia and/or noncardiac chest pain. Of these, 304 (70.8%) were shown to have some kind of esophageal motor abnormality. The most frequent motor abnormality of the esophagus was represented by nonspecific motor disorders (31%), followed by achalasia (13%), whereas the other dysfunctions accounted for a smaller percentage. In particular, diffuse esophageal spasm was shown to be quite rare. It is concluded that esophageal manometry may provide a high diagnostic yield in patients presenting with dysphagia and/or noncardiac chest pain. PMID- 1424827 TI - The Johns Hopkins Swallowing Center database. AB - A special database has been constructed for faculty working in the Swallowing Center of The Johns Hopkins University School of Medicine. The database supports the clinical, research, and publication needs of the Center. This database on swallowing disorders includes over 6000 references to the literature dating from the mid-1960s. The system operates on microcomputer technology and uses relatively inexpensive and intuitive software programs. Monthly updates keep members informed of the latest developments in a multidisciplinary literature. PMID- 1424826 TI - Laryngologic aspects of bolus asphyxiation-bolus death. AB - Among 12,982 forensic autopsies, 78 cases of cafe coronary due to bolus impaction in the larynx (bolus death) were observed from 1947 to 1988. In all cases bolus material occluded the entry to the larynx; only once was a singular occlusion of the glottis observed. The bolus frequently extended into the mouth, trachea, and bronchial tree or esophagus. In all cases small amounts of aspirated material were observed in the deeper parts of the bronchial tree. The most commonly observed bolus was not masticated meat or a meat product. In adults and the elderly the bolus was often too large to pass the physiological narrowings of the hypopharynx. It was commonly lodged above the arytenoid cartilages. Forty-five of the bolus events were observed by bystanders. In 43 of the victims vital reactions were observed by bystanders or at the autopsy. This justifies the hope that many lives could have been saved had the right diagnosis and immediate therapy been initiated. The first step should be manual extraction or use of the Heimlich maneuver; in cases of failure of both attempts, immediate tracheotomy followed by hospitalization and bronchial lavage are indicated. PMID- 1424828 TI - Swallowing problems after excision of tumors of the skull base: diagnosis and management in 12 patients. AB - Acute-onset dysphagia can be a debilitating complication of operative intervention in skull base surgery. A retrospective study performed at Baptist Hospital investigated the oropharyngeal deficits, compensatory swallow techniques, and diet modifications of 12 patients who had undergone excision of skull base tumors. Oropharyngeal dysfunction, reduced laryngeal elevation, and copious pharyngeal retention were the most prominent swallowing deficits. Aspiration occurred in 75% of the patients studied. The most frequently employed compensatory swallow techniques were head turns to the affected side, supraglottic swallow, double swallows, alternating liquids and solids, carbonated beverage swallows, and small bolus size. Approximately 2 weeks following skull base surgery, 58% of the patients were able to tolerate oral intake with the aid of compensatory swallow techniques and diet modifications. Only 1 patient in this group remained unable to tolerate food by mouth. This paper focuses on identification of the disordered components of the swallow and the therapeutic management techniques characteristic of the patient who has undergone excision of a skull base tumor. PMID- 1424829 TI - Scintigraphic detection of salivary aspiration: description of a new diagnostic technique and case reports. AB - Pneumonia is the feared consequence of persistent aspiration of saliva. Although some persons with impaired protection of the laryngeal airway are thought to be at risk, it is not known with certainty which factors are important. Some patients receive tracheostomies to enhance airway safety, often without clear evidence of aspiration of oropharyngeal secretions. A simple, readily available technique is described by which oral secretions are scintigraphically labeled with technetium-99m sulfur colloid via slow intraoral infusion. Subsequent sequential chest imaging with a gamma camera allows detection and tracking of the aspirated material. Three persons are described in whom this technique was used. In one, the scintigraphic analysis was instrumental in implicating infected saliva as the likely source of recurrent pulmonary infections. Although the method is useful in detecting aspiration of saliva in high risk persons, more study is needed to equate the degree of aspiration visualized with the risk of pulmonary disease. PMID- 1424830 TI - Multiple swallows and piecemeal deglutition; observations from normal adults and patients with head and neck cancer. AB - The incidence of multiple swallows for liquid and paste, and the time delay between multiple swallows, was determined from videofluoroscopic records of modified barium swallow tests. In a comparison of liquid and paste, the overall incidence of multiple swallows did not differ, for either patients with head and neck cancer or normal controls. However, for liquid swallows the incidence in patients with cancer was abnormally high, predominantly in patients with pharyngeal cancer. PMID- 1424831 TI - Impact of the diagnostic procedure on outcome measures of swallowing rehabilitation in head and neck cancer patients. AB - This study was designed to determine whether swallow rehabilitation outcomes were affected by the type of evaluation procedure utilized by the clinician. The two evaluation techniques compared were the bedside examination and videofluoroscopy (the modified barium swallow). Ten institutions participated in this study, enrolling a total of 103 partial laryngectomized patients, 21 in the bedside arm and 82 in the videofluoroscopy arm. Data on recovery of oral intake were collected weekly. All patients received an X-ray study of swallow at 3 months after the operation. Mean time to oral intake of food was significantly lower in patients assessed with bedside examination. Overall swallow measures of transit times and swallow efficiencies after 3 months revealed significantly better function in the videofluoroscopy group. Results are discussed in terms of the visibility of swallow physiology with the two assessment techniques, the accuracy of therapy planning with the bedside examination versus videofluoroscopy and the ability of head and neck cancer patients to tolerate some aspiration without developing aspiration pneumonia. PMID- 1424832 TI - Perendoscopic pneumatic dilatation in achalasia: assessment of outcome using esophageal scintigraphy. AB - Sixteen patients (nine male) underwent perendoscopic pneumatic dilatation for achalasia. The Witzel dilator was chosen as it allows placement of the balloon under endoscopic vision. Its efficacy was assessed using esophageal scintigraphy. Symptom score and esophageal transit values at 100 s and after a drink of water all improved significantly (P less than or equal to 0.014) after dilatation and there was a significant correlation between the improved symptom score and the change in transit values after 100 s (r = 0.586, P = 0.017). At follow-up at 8 (3 16) months [mean (range)], 15 of 16 patients (94%) are symptom free. The Witzel dilator is effective in the treatment of achalasia. Esophageal scintigraphy offers a quantitative assessment of esophageal function, helping the clinical investigator evaluate new forms of therapy. PMID- 1424833 TI - Clinical and demographic data in 75 patients with near-fatal choking episodes. AB - The clinical background and circumstances of 75 patients who had survived a near fatal choking episode, i.e., had undergone a Heimlich maneuver, oropharyngeal suctioning, or intubation, is reported. Sixty had choked on a solid bolus (often of a complex texture like sandwiches and chicken soup). Four patients had choked on mashed banana. In 30 patients neurologic disease (such as cerebrovascular disease, Parkinson disease, or dementia) was present. Choking occurred during breakfast (16 patients), lunch (21), dinner (26), and snacks (12). Twenty-five choked at home, 18 in nursing homes, 14 in hospitals, nine in restaurants, and nine in drinking establishments. Twelve were being fed at the time of choking. Fifty-eight of the individuals had oral, pharyngeal, or esophageal abnormalities on radiographic examination that could explain the choking episode. Fourteen patients who were able to vocalize during the choking episode had probably suffered from esophageal impaction. Our study indicates that elderly individuals and those with neurogenic dysphagia are at risk for choking. Dysphagia diet (semisolids) may actually contribute to the risk in these patients. Young adults may also be at risk during episodes of consumption of alcohol and snacks. PMID- 1424834 TI - Dysphagia in cerebral palsy: a comparative study of the Exeter Dysphagia Assessment Technique and a multidisciplinary assessment. AB - Eighteen children with cerebral palsy in a special school, most of whom had feeding difficulties, were studied to compare the diagnostic value of the Exeter Dysphagia Assessment Technique (EDAT) with an exhaustive clinical assessment undertaken by a multidisciplinary team experienced in the diagnosis and treatment of dysphagia of neurological origin. Four feeding skills were assessed by each method independently, viz. anticipation, intraoral sensory perception, oral-motor efficiency, and pharyngeal triggering. Comparison of the two sets of results showed agreement in at least 78% of the assessed skills. The possible reasons for the few discrepancies are discussed. The noninvasive EDAT equipment was easy to use with the children, who had a range of type and severity of cerebral palsy. The test was undertaken in their familiar surroundings and took 15 to 20 min per child. Interpretation of the results showed that EDAT provided a rapid, reliable diagnostic aid which assisted in the assessment of the degree of feeding impairment within each of the four feeding skills tested. PMID- 1424835 TI - Foreign body entrapment in the esophagus of healthy subjects--a manometric and scintigraphic study. AB - Foreign body entrapment and mucosal injury caused by oral medications are increasingly reported to occur in the upper esophagus in apparently normal subjects. We performed esophageal manometry in 40 normal volunteers to determine whether a unique motility pattern in the upper third of the esophagus predisposes to entrapment of foreign bodies at this site; 18 normal volunteers also had transit scintigraphy of a gelatin capsule filled with a radionuclide. The esophageal body was divided into five consecutive segments starting proximally, with each segment corresponding to 20% of the total length. Amplitude, slope, and velocity of the esophageal contraction were markedly decreased in the second segment compared with the other segments. Entrapment and dissolution of a gelatin capsule occurred in 39% of volunteers in the proximal esophagus correlating to the second segment, i.e., the segment with the lowest amplitude, slope, and velocity of esophageal contractions. The observation that wet swallows have greater amplitudes (P less than 0.01) and steeper slopes (P less than 0.05) than dry swallows explains why the occurrence of pill entrapment was reduced when taken with sufficient water. However, even with a water chaser of 120 mL, pill entrapment occurred at the second segment of the esophagus in 1 of 18 volunteers. The observed motility pattern in the proximal esophagus provides a better explanation for the entrapment of foreign bodies at this site than compression of the esophagus by the left main stem bronchus, aortic arch, or left atrium as suggested by other investigators. PMID- 1424836 TI - Velar activity and timing of eustachian tube function in swallowing. AB - Velar motion for dry and liquid swallows was investigated. as well as velar activity in speech, based on X-ray microbeam pellet tracking data. Electromyographic recordings for tensor and levator veli palatini were obtained simultaneously. Velar pellet trajectories for swallowing were more complex than for speech, since there was a high-velocity anterior component in swallowing. For some swallows this anterior component was integrated with velar elevation (especially in liquid swallows), but in other cases initial velar elevation occurred considerably earlier (chiefly in dry swallows). The burst of tensor and levator veli palatini activity characteristic of swallowing was associated with the anterior component of velar pellet motion, but not consistently with velar elevation per se. The conventional view on timing of tensor veli palatini contraction in a swallow, which governs Eustachian tube opening, is that this is associated with velar closure. The X-ray microbeam data suggest rather that Eustachian tube ventilation is more closely associated in time to the onset of pharyngeal peristalsis, which may or may not coincide with initial velar elevation. PMID- 1424837 TI - Oral dysfunction following Nissen fundoplication. AB - In this case report we describe a child with mild neurologic impairment who developed debilitating gagging and retching, and severe oral-motor dysfunction following Nissen fundoplication and gastrostomy tube placement. All oral intake ceased after the operation. Evaluation for postoperative dumping syndrome was negative, and the child's symptoms failed to improve despite numerous medical and surgical measures. However, immediately following reversal of the Nissen fundoplication, the child's gagging and retching ceased, and his oral-motor function began to improve. This is a previously undescribed complication of Nissen fundoplication, a surgical procedure commonly employed in children with neurologic impairment. PMID- 1424838 TI - Postoperative pleural and pulmonary abnormalities in patients undergoing coronary artery bypass grafts. PMID- 1424839 TI - Photodynamic therapy for early stage lung cancer. Preferable to resection? PMID- 1424841 TI - Management of acute empyema. PMID- 1424840 TI - The prognostic value of sputum cytology. PMID- 1424842 TI - Smoke-free hospitals. A time for universal action. PMID- 1424843 TI - Photodynamic therapy in the management of early superficial squamous cell carcinoma as an alternative to surgical resection. AB - Photodynamic therapy has been used since 1980 at our institution for the management of cancer of the tracheobronchial tree. We identified 13 patients (14 cancers) who were thought to be surgical candidates but who elected to have photodynamic therapy. Thirteen cancers (93 percent) had a complete response to hematoporphyrin-derivative phototherapy. Ten cancers (71 percent) showed a complete response after single treatment, and three (21 percent) required a second course of therapy to achieve a complete response. Ten (77 percent) of 13 cancers have shown no local recurrence. Three patients with persistent cancer underwent surgical resection and were found not to have nodal involvement. We concluded that photodynamic therapy is an alternative to surgical resection in the management of early superficial squamous cell carcinoma. PMID- 1424844 TI - Bronchoalveolar lavage in trauma patients for diagnosis of fat embolism syndrome. AB - Fat embolism syndrome (FES) is a rare but serious complication occurring after long bone fractures. Presence of fat droplets in cells obtained by bronchoalveolar lavage has been proposed as a specific tool for FES diagnosis in trauma patients. We evaluated this technique over a 15-month period in 85 patients. Twenty-eight patients were excluded. The remaining 57 patients were divided into three groups: group 1, 26 patients without trauma as control; group 2, 22 patients with trauma but without evidence of FES; and group 3, nine patients with trauma and evidence of FES. Six of 26 patients in group 1 and nine of 22 patients in group 2 exhibited fat droplets in alveolar macrophages, whereas three of nine patients of group 3 had not. This study suggests that (1) presence of fat droplets in alveolar macrophages is not a reliable method for diagnosis of FES after long bone trauma, and (2) many conditions are associated with fat droplets in alveolar macrophages. PMID- 1424845 TI - Sputum cytology-positive, bronchoscopically negative adenocarcinoma of the lung. AB - Among a total of 114 cases of resected lung adenocarcinoma that were examined by sputum cytologic study before bronchoscopy, 17 were sputum cytology-positive, but had no abnormal bronchoscopic findings. In most of these cases, the reason for detection was sputum and bloody sputum (58.8 percent). Pathologically, many cases were classified as stage III A or more (82.4 percent) due to mediastinal lymph node metastases. More than 70 percent of the cases showed vascular invasion. The proportion of well-differentiated cases was also high (52.9 percent). The prognosis of these cases was worse than sputum cytology-negative adenocarcinoma without abnormal bronchoscopic findings and better than sputum cytology-positive adenocarcinoma with abnormal bronchoscopic findings. There was no significant difference between these cases and sputum cytology-negative adenocarcinoma with abnormal bronchoscopic findings. Combined with the bronchoscopic findings, sputum cytologic study is useful for preoperative evaluation of lymph node metastasis and prognosis. This combined approach can provide information necessary to perform sufficient dissection of mediastinal lymph nodes and proper adjuvant therapy in sputum cytology-positive adenocarcinoma cases, even though there are no abnormal bronchoscopic findings. PMID- 1424846 TI - Relationship between pleural changes after myocardial revascularization and pulmonary mechanics. AB - It is known that coronary artery bypass grafting (CABG) results in impairment of postoperative pulmonary function. There is also a high incidence of pleural changes (pleural effusion or pleural thickening) after CABG. We hypothesized that those patients with pleural changes in the postoperative period would have a greater decrease in pulmonary function test (PFTs) results. The present study reports the results of 110 male patients who underwent CABG. The chest films and the PFT results obtained preoperatively and on the sixth postoperative day were reviewed. The relationship between pleural changes and PFTs was analyzed in patients who received saphenous vein graft alone (SVG group: 50 patients) or in combination with internal mammary artery grafting (IMA group: 60 patients). In the IMA group, the patients who had pleural changes had significantly greater decreases in their pulmonary function than did the patients without pleural changes. The decrease in the FVC, TLC and FEV1 in the patients with pleural effusions (37.6, 27.8 and 36.8 percent) was similar to that in patients with pleural thickening (34.6, 28.3 and 35.0 percent) and both were significantly greater (p < 0.05) than the changes in the patients with a normal radiograph (26.1, 17.6 and 26.9 percent). In the SVG group, the presence of pleural changes was not significantly related to the decrement in pulmonary function. The values of RV, FRC, Cst, and blood gases were not affected in the SVG or IMA group by the presence of pleural changes. We conclude that the presence of pleural changes on the chest radiograph is associated with a larger decrement of pulmonary function after CABG in the IMA group. This larger decrease probably reflects added thoracic trauma and is not due to the presence of pleural changes per se. PMID- 1424847 TI - Arterial blood gases after coronary artery bypass surgery. AB - Coronary artery bypass graft (CABG) surgery adversely affects arterial blood gas (ABG) determinations. The purposes of this study were to assess serial changes in ABGs following bypass surgery and identify factors that may influence these changes. Room air ABGs were obtained preoperatively and on days 1, 2, 4, 6, and 8 postoperatively on 125 patients undergoing bypass surgery. Fifty-five patients (saphenous vein grafting [SVG] group) had only SVG grafting while 70 (internal mammary artery [IMA] group) received one (60 patients) or two (10 patients) IMA grafts in addition to the SVG grafts and were subjected to pleurotomy. The mean preoperative values (+/- SD) were as follows: PaO2, 75.1 +/- 7.7 mm Hg, P(A-a)O2, 20.9 +/- 7.5 mm Hg; PaCO2, 33.6 +/- 4.1 mm Hg; pH, 7.43 +/- 0.04; hemoglobin, 14.8 +/- 1.4 g/dl; and hematocrit, 44.2 +/- 3.9 percent. There was a large decrease in the PaO2 postoperatively. The nadir for the PaO2 (55.7 +/- 6.6 mm Hg) occurred on the second postoperative day. Eight days postoperatively, there were still significant abnormalities; the PaO2 was 65.7 +/- 7.3 mm Hg, the P(A-a)O2 was 33.2 +/- 8.8 mm Hg; the hemoglobin was 10.5 +/- 1.4 g/dl; and the hematocrit was 31.7 +/- 4.0 percent. The decrease in the PaO2 was particularly noteworthy given the large decrease in the hemoglobin and hematocrit. The changes in the PaO2 were not significantly correlated with the age, number of grafts, pump time, length of anesthesia, or endotracheal intubation or smoking history. Immediately postoperatively, changes were similar in both groups (p > 0.05); on the second postoperative day, the PaO2 had decreased 26.9 percent in the SVG group and 25.5 percent in the IMA group. However, the postoperative abnormalities resolved more slowly in the IMA group (p < 0.05). These observations suggest that the additional trauma to the lungs and chest wall in the IMA group (pleurotomy, the placing of pleural drains, etc) will result in a longer recovery time in the IMA group than in SVG group. PMID- 1424848 TI - An evaluation of severity-modulated compliance with q.i.d. dosing of inhaled beclomethasone. AB - Although the asthmatic subject's compliance with a regimen of inhaled corticosteroids is often poor, it has been suggested this may improve during periods of increased severity. To test this, we measured daily peak expiratory flow rates (PEFRs), asthma symptoms, and the use of an albuterol inhaler over nine weeks period in ten patients with moderately severe asthma. The effect of changes in these severity indices on compliance with a q.i.d. regimen of inhaled beclomethasone was evaluated. The PEFR was measured in the morning before bronchodilator administration, and symptoms were graded on a scale of 4 to 16, while albuterol and beclomethasone inhalations were electronically recorded. Three measures of compliance with the beclomethasone regimen were used: (1) mean daily compliance ([number of inhalations/number of prescribed inhalations] x 100); (2) underuse, ie, the percentage of days with less than the prescribed number of inhalations; and (3) overuse, ie, the percentage of days with greater than the prescribed number of inhalations. Mean daily compliance was 67 +/- 36 percent, while underuse was observed in 69 percent and overuse in 11 percent of the days. Despite clinical exacerbations in six of the ten patients and considerable variation in the severity indices, no significant relationship was found between the change in asthma severity and compliance with the beclomethasone regimen. These findings do not support the concept of severity modulated compliance with inhaled corticosteroids. PMID- 1424849 TI - Performance evaluation of three vaporizing humidifiers and two heat and moisture exchangers in patients with minute ventilation > 10 L/min. AB - STUDY OBJECTIVE: To compare the thermal and humidification capacity of three heated hot water systems (HHWSs) and two heat and moisture exchangers (HMEs) in ICU patients submitted to minute ventilation > 10 L/min. DESIGN: Prospective, controlled, randomized, not blinded study. SETTING: ICU of a university hospital. PATIENTS: ICU patients requiring controlled mechanical ventilation with minute ventilation > 10 L/min. Patients had to be sedated and paralyzed and had to require ventilation for more than four days. INTERVENTIONS: Following a randomized order, the patients were ventilated for 24-h periods with three HHWSs (Bennett Cascade 2 humidifier, Fisher-Paykel MR 460 and MR 600) and two HMEs (Pall Ultipor and Hygrobac filter). MEASUREMENTS AND RESULTS: In each patient and for each 24-h period, absolute humidity, (AH), relative humidity (RH) of inspired gases, and tracheal temperature were obtained. Two HHWSs (Bennett and Fisher Paykel MR 460) had a better thermal and humidification capacity than any other systems (p < 0.001). The hydrophobic HME (Pall filter) had a poor thermal and humidification capacity (RH: 79 +/- 8.7 percent; AH: 20.6 +/- 2.3 mg H2O/L). The hygroscopic filter (Hygrobac filter) had better thermal and humidification capacity than the Pall filter (RH: 92.5 +/- 3.6 percent; AH: 29.1 +/- 1.8 mg H2O/L; p < 0.001). Tracheal temperature was well preserved by all systems. The thermic and humidification capability of the Hygrobac filter declined over 24 h. Since the Pall filter could not achieve an AH > 25 mg H2O/L in any patient, it was not studied beyond the first measurement. CONCLUSIONS: The Hygrobac filter had a thermal and humidification capability closed to the two HHWSs (81 to 97 percent) but the capability declines over 24 h. The Pall filter had a poor capability (54 to 74 percent of that of HHWSs). PMID- 1424850 TI - Inspiratory muscle training combined with general exercise reconditioning in patients with COPD. AB - We compared, in a controlled clinical trial, the effect of specific inspiratory muscle training combined with general exercise reconditioning, for six months, with that of general exercise reconditioning alone on inspiratory muscle strength, endurance, and exercise performance in patients with COPD. Thirty-six patients were recruited into three groups; 12 patients received specific inspiratory muscle training combined with general exercise reconditioning, 12 patients underwent general exercise reconditioning alone, and the remaining 12 patients received no training. Specific inspiratory muscle training, for six months, improved the inspiratory muscle strength and endurance in patients with COPD. This training combined with general exercise reconditioning also provided improvement in exercise tolerance, and this improvement was significantly greater than that of general exercise reconditioning alone. PMID- 1424851 TI - Inspiratory muscle training in patients with bronchial asthma. AB - In patients with asthma, the respiratory muscles have to overcome the increased resistance while they become progressively disadvantaged by hyperinflation. We hypothesized that increasing respiratory muscle strength and endurance with specific inspiratory muscle training (SIMT) would result in improvement in asthma symptoms in patients with asthma. Thirty patients with moderate to severe asthma were recruited into 2 groups; 15 patients received SIMT (group A) and 15 patients were assigned to the control group (group B) and got sham training in a double blind group-comparative trial. The training was performed using a threshold inspiratory muscle trainer. Subjects of both groups trained five times a week, each session consisted of 1/2-h training, for six months. Inspiratory muscle strength, as expressed by the PImax at RV, increased significantly, from 84.0 +/- 4.3 to 107.0 +/- 4.8 cm H2O (p < 0.0001) and the respiratory muscle endurance, as expressed by the relationship between Pmpeak and PImax from 67.5 +/- 3.1 percent to 93.1 +/- 1.2 percent (p < 0.0001), in patients of group A, but not in patients of group B. This improvement was associated with significant improvements compared with baseline for asthma symptoms (nighttime asthma, p < 0.05; morning tightness, p < 0.05; daytime asthma, p < 0.01; cough, p < 0.005), inhaled B2 usage (p < 0.05), and the number of hospital (p < 0.05) and sick-leave (p < 0.05) days due to asthma. Five patients were able to stop taking oral/IM corticosteroids while on training and one in the placebo group. We conclude that SIMT, for six months, improves the inspiratory muscle strength and endurance, and results in improvement in asthma symptoms, hospitalizations for asthma, emergency department contact, absence from school or work, and medication consumption in patients with asthma. PMID- 1424852 TI - Quantitative assessment of dyspnea during exercise before and after bullectomy for giant bulla. AB - Incremental exercise testing using a cycle ergometer was performed in eight patients with giant bulla before and after bullectomy to assess dyspnea. There was a significant positive linear relationship between dyspnea expressed in the Borg scale (BS) and oxygen consumption (VO2) during exercise in all subjects. From these correlations, we introduced the following three new parameters for quantitative assessment of dyspnea: the Borg scale slope (BSS); the threshold load of dyspnea (TLD); and the breakpoint load of dyspnea (BLD), representing the slope of the regression line, onset of dyspnea on the regression line, and the maximum oxygen consumption before the subjects interrupted exercise, respectively. After surgery, the BSS showed marked decrease, and the TLD and BLD showed significant increase. Therefore, the reduction in the dyspnea with peak exercise after surgery was thought to be, at least in part, based on the delay of dyspnea onset, the decrease in dyspnea sensitivity, and the improvement in exercise capacity. The improvement in dyspnea during exercise in patients with giant bulla after surgery was extensively evaluated by newly introduced parameters based on BS-VO2 regression line. PMID- 1424853 TI - Pulse oximetry in the postoperative care of cardiac surgical patients. A randomized controlled trail. AB - STUDY OBJECTIVE: To demonstrate the utility of pulse oximetry in detecting clinically unapparent episodes of arterial desaturation in postoperative cardiac surgical patients and to evaluate the effect of pulse oximetry on ordering arterial blood gas analyses. DESIGN: Prospective, randomized, partially blinded comparison. SETTING: Cardiothoracic surgical intensive care unit. PATIENTS: 35 patients following elective cardiac surgical procedures. INTERVENTIONS: All patients were monitored continuously with pulse oximetry throughout their ICU course. In group 1 patients, the SpO2 data were available at the bedside. In group 2 patients, the SpO2 data were masked at the bedside and monitored at a remote location. MEASUREMENTS AND RESULTS: Utilization of pulse oximetry allowed a significant reduction in arterial blood gas utilization in group 1 (group 1: 12.4 +/- 7.5 blood gas analyses per ICU admission vs group 2: 23.1 +/- 8.8; p = 0.0007) without adverse events. Clinically unapparent desaturations were detected in 7 of 15 patients in group 2. CONCLUSIONS: Pulse oximetry improves patient safety through the detection of clinically unapparent episodes of desaturation and can allow a reduction in the number of blood gas analyses utilized without adverse effects to the patient. This may allow a potential cost savings to the patient. PMID- 1424854 TI - Cardiovascular risk factors in snorers. A cross-sectional study of 3,323 men aged 54 to 74 years: the Copenhagen Male Study. AB - Former studies on the association between snoring and cardiovascular disease (CVD) have only partly taken established CVD risk factors into consideration. In the Copenhagen Male Study, 3,323 men aged 54 to 74 years were classified according to self-reported snoring habits. Eleven CVD risk factors were examined. The prevalence of snoring decreased with age, with a 50 percent higher frequency of snorers among the youngest quintile than among the oldest (p < 0.00001). Snoring, age adjusted, was positively associated with tobacco smoking (p < 0.001), alcohol consumption (p < 0.001), body mass index (BMI) (p < 0.0001), serum triglyceride level (p < 0.01), systolic blood pressure (p < 0.05) and nearly significantly associated with diastolic blood pressure (p = 0.07). Snorers were less physically active in leisure time than others (p < 0.01). The association between self-reported snoring and blood pressure disappeared when other factors, including BMI, were taken into consideration. No significant associations were found between snoring and social class, snoring and low- or high-density lipoprotein or between snoring and hypertension. We conclude that snoring is associated with major cardiovascular risk factors. Accordingly, it is evident that in studies on snoring and CVD, proper controlling for the influence of potential confounders is a sine qua non. PMID- 1424855 TI - Measurement of mucociliary transport velocity in ventilated patients. Short-term effect of general anesthesia on mucociliary transport. AB - OBJECTIVES: The objectives of this study were to evaluate a method for measuring BTV in ventilated patients and to study the short-term effect of general anesthesia with midazolam, Fentanyl, pancuronium and O2:N2O on BTV. DESIGN: The study included phantom measurements on a bronchoscopy model and the determination of BTV in patients in a convenience sample trial. SETTING: The study took place in a university hospital. PATIENTS: Fourteen patients undergoing major abdominal surgery with planned postoperative mechanical ventilation were included in the study. All patients gave their written informed consent to participate in the study. INTERVENTIONS: Bronchial mucus transport velocity was measured with a small volume (0.05 to 0.08 ml) of technetium 99m-labeled albumin microspheres with an activity of 3 MBq. The radiolabeled bolus was deposited on the dorsal mucosal surface at the distal end of the right and left main bronchus via flexible bronchoscopy. The movement of the microspheres toward the trachea was visualized and recorded using a scintillation camera; quantitative evaluation utilized the condensed image. MAIN MEASUREMENTS AND RESULTS: The technique was validated in a bronchoscopy model and in an intubated patient by moving a radioactive drop in a catheter through the main bronchi at velocities from 0 to 20 mm/min. The velocities determined by the image processing technique correlated well with the data by the model and patient determination (right bronchus, r = 1.0; left bronchus, r = 1.0). In seven ventilated patients, mechanical irritation by the fiberscope produced no significant effect on BTV. The BTV was measured preoperatively in seven conscious patients one day before surgery while they received local anesthesia with 10 ml of 1 percent lidocaine and postoperatively while they received intubation anesthesia. The preoperative and postoperative BTV values showed no significant differences (10.5; 5.7 to 13.7 mm/min; vs 9.7 (3.7 to 15.3) (median with range). CONCLUSION: By this method, bronchial transport velocity can be determined in a relatively short time in ventilated patients. General anesthesia with midazolam, Fentanyl, pancuronium and O2:N2O does not influence BTV. PMID- 1424857 TI - Inpatient management of status asthmaticus. AB - We examined physician management of patients hospitalized for status asthmaticus at a university hospital. A retrospective review of consecutive admissions for status asthmaticus covering a 13-month period yielded 130 charts for review. We found that practice patterns with respect to documentation of severity of illness, medications, and documentation of efficacy of therapy fell short of the current state of knowledge with respect to treatment of asthma. Asthma is a treatable disease, and physician education needs to bridge the gap between current practice patterns and standards of optimal therapy as defined in the literature. PMID- 1424856 TI - Two-year bronchodilator treatment in patients with mild airflow obstruction. Contradictory effects on lung function and quality of life. AB - In a two-year randomized controlled study, we studied the effects of bronchodilator treatment on the lung function and the quality of life in patients with mild airflow obstruction. The patients were randomly divided to receive either continuous or symptomatic bronchodilator treatment. Within these treatment groups, they received salbutamol in the first year and ipratropium bromide in the second or vice versa. In addition, the quality of life of the patients was compared to that of the general population. One hundred and forty-four patients completed the study. When compared to the general population, these patients showed a serious impairment in quality of life. No differences between the two drugs were found, but the results indicated that FEV1 decline in the continuously treated group was significantly larger than in the symptomatically treated group. However, this was not reflected in a significant deterioration of the quality of life in the continuous group as measured by means of the Nottingham Health Profile and the Inventory of Subjective Health. Decline in FEV1 showed no correlation with changes in quality of life scores. This may be due to a relatively rapid adjustment of the patients to a decline in FEV1, as a result of which it has no direct effect on the experienced quality of life. Another reason may be that continuous bronchodilation masks the worsening of the disease. This lack of awareness might in turn be caused by the continuous symptom relief of bronchodilators. PMID- 1424858 TI - Effect of nasal continuous positive airway pressure on cardiac output and oxygen delivery in patients with congestive heart failure. AB - We studied the acute hemodynamic effects of increasing nasal continuous positive airway pressure (CPAP) in 13 patients with acute decompensation of congestive heart failure. Heart rate, respiratory rate, pulmonary capillary wedge pressure, right atrial pressure, systemic blood pressure, and thermodilution cardiac outputs were measured at baseline, during, and after application of nasal CPAP at increasing pressures of 5, 10, and 15 cm H2O. Cardiac index, stroke volume, and oxygen delivery were calculated. Based on a significant change in cardiac output greater than or equal to 400 ml, seven patients were classified as responders, whereas six patients were considered to be nonresponders. In responders, significant increases were noted in cardiac index (2.5 +/- 0.7 to 2.9 +/- 0.9 L/min/m2), stroke volume (49 +/- 15 to 57 +/- 16 ml), and oxygen delivery (10.3 +/- 5.1 to 12.3 +/- 6.0 ml/min/kg) without a change in pulmonary capillary wedge pressure. In contrast, the nonresponders showed no significant change in any of the hemodynamic parameters. Improvement in cardiac output could not be predicted by any of the baseline hemodynamic or clinical variables, nor was it related to random variations since all variables returned to baseline after cessation of CPAP. Increase in stroke volume without a change in pulmonary capillary wedge pressure (preload) suggests either improved inotropic function of the left ventricle or reduced left ventricular afterload with CPAP. Thus, CPAP may offer a new noninvasive adjunct to improving left ventricular function and augmenting cardiac performance in a subset of patients with congestive heart failure. PMID- 1424859 TI - Intracranial hemodynamics in sleep apnea. AB - Intracranial pressure changes and poor cerebral perfusion have been reported in sleep apnea syndrome (SAS), but such studies have been limited due to lack of a reliable noninvasive study method. We determined the systolic (VS), diastolic (VD), and mean (VM) cerebral blood flow velocities of the middle cerebral artery in 23 individuals (12 severe SAS patients and 11 control subjects) using transcranial Doppler sonography before sleep, during sleep (NREM and REM) and upon awakening. All three velocities (VS = 87.4 cm/s compared to 104.7 cm/s, VD = 41.6 cm/s compared to 47.7 cm/s, and VM = 57.0 cm/s compared to 67.0 cm/s) were decreased in patients with SAS and VS and VM were significantly lower than in control subjects (p = 0.005 and p = 0.033, respectively). The end-tidal CO2 (PETCO2) in the SAS patients (47.3 mm Hg) compared to the control subjects (41.8 mm Hg) was significantly higher (p = 0.003). When the VM was adjusted to normalized CO2 using the Markwalder's equation, the reduction in velocity in patients with SAS (47.5 cm/s) compared to control subjects (63.0 cm/s) became more significant (p = 0.005). This study shows that cerebral blood flow velocities are lower in patients with SAS compared to control subjects and that transcranial Doppler sonography may be useful in such evaluations. PMID- 1424860 TI - Short- and long-term hemodynamic effects of captopril in patients with pulmonary hypertension and selected connective tissue disease. AB - To assess the pulmonary and systemic hemodynamic effects of oral captopril in patients with connective tissue disease and pulmonary hypertension, we performed right heart catheterization in eight patients with diffuse systemic sclerosis, the CREST syndrome, or mixed connective tissue diseases prior to and immediately following administration of captopril (dose range 12.5 to 50.0 mg, short-term study). Four of these patients underwent repeat right heart catheterization after three to six months of oral captopril therapy (long-term study). In the short term study, oral captopril produced a significant decrease in mean pulmonary vascular resistance from 6.2 +/- 3.6 to 4.6 +/- 3.8 units (p < 0.01). This was accompanied by a significant decrease in mean pulmonary artery pressure, mean blood pressure, mean systemic vascular resistance and a significant increase in cardiac output. Similar changes in pulmonary hemodynamics were noted in the long term study. Thus, oral captopril is capable of producing an acute and sustained reduction in pulmonary vascular resistance in patients with pulmonary hypertension associated with the aforementioned connective tissue diseases. PMID- 1424861 TI - Clinical experience and physiologic results with an implantable intratracheal oxygen catheter. AB - Ten patients with chronic lung disease received an implanted ITOC. Seven patients continue to use their catheters after a mean period of 14.75 months. Four catheters were removed, 2 at 1 month, 1 after 10 months and 1 after 13 months. One patient requested a second catheter. Three patients experienced mucus plug formation; this was transient in two patients, but led to removal of the catheter in the third. To determine the degree of oxygen-saving afforded by the ITOC, SaO2 was measured at rest and during exercise for eight of the ten subjects using a double-blind technique. The calculated oxygen savings were around 40 percent both at rest and during exercise. The ITOCs were well received by the majority of our patients and were shown to produce a useful saving of oxygen which is of benefit to patients using portable systems and those who require high oxygen flow rates. PMID- 1424862 TI - A discriminant analysis applied to methacholine bronchoprovocation testing improves classification of patients as normal, asthma, or COPD. AB - Two discriminant functions, incorporating baseline measurements of pulmonary function and measures of airway responsiveness, were developed to improve patient classification into groups of normal, asthma, or COPD. Accuracy of group classification was compared between the usual laboratory method (single discriminating cut-off) and these new mathematically developed functions. Forty five normal subjects, 27 asthmatic patients, and ten well-defined COPD patients were entered into the analysis. Measurements of airway responsiveness were determined by measurement of both specific airway conductance (SGaw) and spirometry (FEV1) after sequential inhalation of methacholine. RESULTS: A single discriminant cut-off using measures of SGaw (PD35) or FEV1 (PD20) does not sufficiently discriminate asthma from groups that contain normal and COPD subjects (67 to 71 percent predictive value). On the other hand, our discriminant functions demonstrated improved patient classification (positive predictive value, 88 to 89 percent). We conclude that bronchoprovocation tests used to evaluate the diagnosis of asthma should incorporate measures of baseline lung function into the analysis. This, we believe, is especially necessary when baseline lung function demonstrates minimal airflow obstruction and the possibility of other causes of airway disease exist. PMID- 1424863 TI - Prevention and treatment of glucocorticoid-induced osteoporosis. A pathogenetic perspective. AB - Since the discovery of cortisol and the synthesis of related compounds, these potent pharmacologic agents have been progressively more widely utilized in allergic, pulmonary, and rheumatologic conditions. Organ transplantation represents a new group of patients added to the already large pool of subjects receiving glucocorticoids. However, glucocorticoids cause major side effects involving several organ systems, including the cardiovascular, endocrine, gastrointestinal, ophthalmologic, and musculoskeletal systems. Among the most dramatic side effects is the development of glucocorticoid-induced osteoporosis. Glucocorticoid use in the treatment of chronic obstructive pulmonary disease accounts for the majority of male patients with osteoporosis seen in our mineral metabolism clinic. This article focuses on glucocorticoid-induced osteoporosis in the adult with an emphasis on the clinical aspects of this condition. It is intended not as an extensive review on the subject but as a practical guide to help clinicians prevent and treat this condition in adult patients. PMID- 1424864 TI - The usefulness of step sectioning of transbronchial lung biopsy specimen in diagnosing sarcoidosis. AB - To evaluate the usefulness of step sectioning of the transbronchial lung biopsy (TBLB) specimens obtained from patients with suspected sarcoidosis, we examined all TBLB specimens obtained from 132 patients who were diagnosed clinically as having sarcoidosis at our institute. When routine sections of TBLB specimens did not show sarcoid granuloma, we prepared additional serial sections from each block and stained every fifth section with hematoxylineosin (step sectioning). All step sections were examined histologically. With the aid of step sectioning, the diagnostic yield of sarcoidosis increased from 38 percent (18/47) to 47 percent (22/47) in stage 1 patients, and from 57 percent (37/65) to 82 percent (53/65) in stage 2 patients. All of the newly detected granulomas were identified between the first and seventh sections. We conclude that step sectioning is useful method in diagnosing sarcoidosis. PMID- 1424865 TI - Long-term outcome of pediatric sarcoidosis with emphasis on pulmonary status. AB - Sixty-one pediatric and adolescent patients (age < or = 16 years) with sarcoidosis proved by biopsy specimen were identified during the period 1957 to 1976; 19 patients with elapsed time from diagnosis of 8 to 35 years (mean, 21 years) were reexamined in 1985. Age at onset of disease ranged from 4 to 16 years (mean, 12.5 years). Sex distribution was equal; 68 percent of individuals were black. At follow-up, clinical evaluation, chest roentgenograms, pulmonary function tests, electrocardiograms (ECGs), echocardiograms (ECHO), and angiotensin-converting enzyme (ACE) activity were performed on each subject. In addition, complete blood cell counts, erythrocyte sedimentation rates, serum calcium, immunoglobulin levels, B- and T-cell enumerations, and intradermal skin tests for delayed hypersensitivity were also obtained. Although all initial pediatric chest roentgenograms were abnormal, at follow-up only 37 percent were abnormal. Pulmonary function test results were available for ten children, and 90 percent were decreased. In 1985, 68 percent of the adults had abnormal lung function; furthermore, eight patients had reduced diffusing capacities, one had hypoxemia, and two had elevated ACE activity. Specific abnormalities were noted on two ECGs and 12 ECHOs. One individual had an elevated sedimentation rate, while another had an increased serum calcium level. Six patients had elevated IgA values, two had elevated IgM values, and two had depressed IgM values; IgG values were normal in all subjects. B- and T-cell percentages were unremarkable in all patients tested. Four individuals were anergic to skin test antigens. Long-term pulmonary morbidity was observed in four patients; in addition, one of these and four others suffered nonpulmonary sequelae. These results are in agreement with those of other investigators, but insufficient data still exist on the long-term effects of sarcoidosis on the pediatric host. PMID- 1424866 TI - Thoracoscopic resection of pulmonary metastases. AB - OBJECTIVE: To describe the use of thoracoscopic techniques to achieve parenchymal sparing wedge resection of peripheral lung lesions in patients with a history of malignancy, and to describe the morbidity, mortality, and hospital course associated with this approach. DESIGN: Case series. SETTING: University hospital. PARTICIPANTS: Patients with a history of malignancy and lesions on computerized tomography in the outer one third of the lung parenchyma. MAIN OUTCOME MEASUREMENTS: Histologic analysis of resected lung lesions, operative findings, operative time, duration of chest tube drainage and hospital stay, operative morbidity, and mortality. RESULTS: Twenty-one thoracoscopic resections of pulmonary parenchymal lesions were performed on 15 patients. All peripheral lesions identified by computerized tomography were found at thoracoscopy and successfully resected with the Nd:YAG laser (n = 7), an endoscopic stapler (n = 10), or both (n = 4). The mean diameter of the lesions was 0.8 cm (range 0.2 to 1.5 cm). Histologic analysis revealed metastatic disease in 13 patients and benign disease in 2 patients. All resection margins were free of tumor. The mean duration of chest tube drainage and postoperative hospital stay were 1.8 +/- 0.1 and 3.3 +/- 0.1 days, respectively. Mean operative time was 111 min (range 45 to 155 min). One patient who underwent a right thoracoscopic resection developed a transient left vocal cord paresis. There were no other complications and no deaths. CONCLUSION: Thoracoscopy was successful in identifying peripheral lung lesions and allowed for parenchymal sparing resection identical in extent to that performed with open approaches. For select patients with peripheral lung nodules felt to be metastases, thoracoscopic resection may result in reduced morbidity, cost, hospital stay and allow for more rapid institution of therapy for the primary disease. PMID- 1424867 TI - Mycobacterium kansasii infection following primary pulmonary malignancy. AB - The purpose of this study was to determine whether any of the Mycobacterium kansasii cases were the consequences of primary lung malignancy. The records and chest x-ray films of 295 patients with M kansasii pulmonary infection were reviewed. The infection was found to complicate the primary lung neoplasm in four cases. Three patients had had treatment for malignancy: one patient with small cell carcinoma received chemotherapy, steroids and radiation; one with adenocarcinoma underwent a lobectomy and radiation; and the third patient had a lobectomy and radiation for malignant fibrohistiocytoma. The fourth patient developed the infection three years after lung malignancy manifested itself, which was only a few months before the clinical evidence of distant metastasis with adenocarcinoma was detected. We suggest that this infection be considered in patients from M kansasii endemic areas, especially after they have received radiation treatment for lung malignancy. This association has never been described before. PMID- 1424868 TI - Role of chronic Pseudomonas aeruginosa infection in the development of bronchiectasis. AB - To understand the role of Pseudomonas aeruginosa infection in the development of bronchiectasis, we investigated by CT the presence of bronchiectasis in two groups of chronic bronchitis patients and in a control group. There were no differences in clinical or laboratory findings between groups A and B. Three observers without any knowledge of these patients reported bronchiectasis on a scale of 0 to 3 and bronchial wall thickness on a scale of 0 to 3 in each lobe of both lungs. Bronchiectasis and wall thickness scores in group A (chronic bronchitis with P aeruginosa infection) were significantly higher than bronchiectasis scores and wall thickness in group B (chronic bronchitis without P aeruginosa infection). Both scores in group B were higher than those in group C (control group). These findings support the idea that chronic P aeruginosa infection plays a role in the development of bronchiectasis. PMID- 1424869 TI - Immunosuppressive acidic protein in patients with lung cancer. AB - Using a single radial immunodiffusion method, serum immunosuppressive acidic protein (IAP) was determined in 117 patients with primary lung cancer, 34 patients with benign lung disease, and 45 healthy control subjects. The mean value of IAP for patients with lung cancer was significantly higher than that of normal control subjects. There were no significant differences in IAP levels among different histologic types and among different stages of lung cancer. It was concluded that serum IAP level was elevated in patients with lung cancer, especially during the early postoperative period, and serial measurements of serum IAP were of value in monitoring lung cancer patients. PMID- 1424870 TI - Long-term effects of hormone replacement therapy on Doppler-derived parameters of aortic flow in postmenopausal women. AB - Eighteen postmenopausal women were examined by Doppler echocardiography before initiation of HRT (T1), then after ten weeks (T2) and one year (T3). This study group was compared with another in which HRT was not used. Flow velocity integral, which correlates with SV, and MA, an indicator of cardiac contractility, were calculated. In the study group, PFV was 107 +/- 18 cm/s at T1 and increased significantly at T2 and T3. Ejection time, which was prolonged at T2 compared to T1, returned to its basal value at T3. Flow velocity integral increased at T2, but this change was only partially sustained at T3. Mean acceleration maintained its increase throughout T2 to T3. None of the Doppler parameters showed a significant change in the controls from T1 to T3. Our results suggest that the peripheral hemodynamic effects of HRT, such as vasodilatation, are transient, whereas the central effects (increased inotropism) are long lasting. PMID- 1424871 TI - Clinical risk assessment after first myocardial infarction--is additional noninvasive testing necessary? AB - In order to assess whether the outcome of MI can be predicted by clinical data alone or whether and how much noninvasive testing is necessary to predict cardiac events or death, 361 patients were prospectively evaluated and followed for up to five years. A recursive partitioning analysis indicated that high-risk patients can be identified clinically after MI with a high degree of accuracy; to separate low-risk patients who need no further investigation or therapy, however, one additional noninvasive test is necessary which allows quantification of myocardial damage as well as exercise-induced ischemia. Additional tests added little to this risk prediction, indicating that multiple noninvasive testing should not be performed. PMID- 1424872 TI - Rapid left ventricular filling in untreated hypertensive subjects with or without left ventricular hypertrophy. AB - In this study, independent contribution of age, HR, BMI, casual and ambulatory blood pressure, LVM and LVEF in evaluating diastolic filling have been investigated in 34 never-treated hypertensive patients and in 15 healthy normotensive subjects. All the subjects were free from coronary artery disease, valvular disease, heart failure, renal disease and psychiatric problems. All the hypertensive subjects (never treated) were subgrouped according to presence or absence of LVH. The PFR decreased significantly and tPFR increased significantly in hypertensive patients in comparison with normotensive subjects and they did not change in the presence vs absence of LVH. The PFR was inversely correlated with BMI, age, 24-h mean SBP and with 24-h DBP. In multiple regression analysis, PFR decreased with BMI, age, 24-h mean SBP and DBP but not with LVMI. These results suggest that BMI, age and 24-h mean blood pressure were the major determinants of PFR abnormalities in hypertensive patients. PMID- 1424874 TI - Rhodotorula rubra contamination in fiberoptic bronchoscopy. AB - Rhodotorula rubra was recovered in 18 bronchoscopic specimens from 15 patients from May to November 1987. One hundred and twenty-one bronchoscopies were performed during that period by two bronchoscopists (W. W.; R.D.) at Letterman Army Medical Center in San Francisco. Isolation of R rubra occurred in 11 bronchoalveolar lavage (BAL) specimens, four bronchial washes, and three transbronchial biopsies. Clinical infection was not present in any of these patients, although five were immunocompromised hosts. After a stepwise infection control review of the laboratory, the bronchoscopy suite, bronchoscopists, and the fiberoptic bronchoscope failed to recover the organism, a systematic evaluation of the cleaning procedure was undertaken. We discovered that replacement of the suction valve and the rubber biopsy valve on the biopsy channel immediately after cleaning allowed moisture to accumulate in these areas. Removal of both the suction valve and biopsy valve during periods of nonuse resulted in adequate drying of the biopsy channel and eradication of contamination from December 1987 to May 1990 (350 bronchoscopies). Epidemiologic and infection control surveillance is critical for bronchoscopy, especially when possible pathogens are recovered by BAL in the immunocompromised patient. PMID- 1424873 TI - Accuracy of capnography in nonintubated surgical patients. AB - Previous studies have reported mixed results when correlating etCO2 and PaCO2 in mechanically ventilated patients with underlying respiratory disease. However, the utility and accuracy of capnography in nonintubated patients, without chronic pulmonary disease, has received little attention. We studied 25 nonintubated surgical patients to (1) examine the correlation between PaCO2 and etCO2 and (2) describe the relationship between dead space (VD/VT), venous admixture and P(a et)CO2. End tidal CO2 was lower than PaCO2 by an average of 3.6 mm Hg. Regression analysis found a close correlation between dead space and the P(a-et)CO2 gradient (r = 0.77, p < 0.001), while venous admixture was of lesser importance (r = 0.47). Capnographic estimates of PaCO2 can be useful for continuously monitoring the respiratory status of nonintubated spontaneously breathing patients weaned from mechanical ventilation. This may be of particular value in trauma victims and in selected surgical patients without underlying respiratory disease in whom other injuries require continued critical care. PMID- 1424875 TI - Cardiac isoenzymes following heart transplantation. AB - Creatine phosphokinase (CPK) isoenzymes are commonly obtained after heart transplantation (HT) to assess myocardial injury of the donor heart. This investigation retrospectively evaluated the utility of this practice. Fifty-six recipients of orthotopic heart transplants had at least two daily CPK-MB studies following HT. All patients were followed up for at least one year (or until death). Nineteen patients had entirely negative CPK-MB determinations (NEG). Eighteen patients had a single positive CPK-MB determination, and were considered to be equivocal (EQUIV). Nineteen patients had more than one daily positive CPK MB determination (POS). To evaluate the influence of positive CPK-MB determinations on the outcome of HT, we compared the results in the NEG and POS groups. There was no difference in the donor organ ischemic times between the two groups. The duration of follow-up for the two groups was also similar (1,192 days vs 1,020 days). The NEG and POS groups had no significant difference in: 1 year survival (84 percent vs 74 percent); freedom from treated rejection episodes in 3 months (39 percent vs 42 percent); and freedom from coronary artery disease (CAD) at 3 years (83 percent vs 86 percent). Additionally, the ejection fractions of the donor hearts were similar at 1 year post-transplant for the 2 groups (64 percent vs 59 percent). We conclude that myocardial injury, as reflected by post transplant CPK-MB levels, does not predict one-year mortality, predisposition to rejection, predisposition to coronary artery disease, or ultimate graft dysfunction. In an effort to perform HT more economically, we no longer obtain CPK-MB levels following HT. PMID- 1424876 TI - Preoperative corticosteroids. A contraindication to lung transplantation? AB - Regular preoperative application of corticosteroids has been considered as a contraindication to lung transplantation for fear of an increased risk of postoperative morbidity and mortality. Recently, however, we have accepted patients for transplantation in whom treatment with steroid medication could not be terminated preoperatively. Up to February 1991, 27 unilateral and bilateral transplantations in 26 patients were analyzed. Corticosteroid therapy was discontinued at least three months prior to transplantation in 13 patients (group 1), whereas in 14 cases, the patients continued their daily corticosteroid therapy to the time of transplantation (prednisolone, 0.1 to 0.3 mg/kg/day; group 2). There were no significant differences between the groups with respect to sex, age, diagnosis, or type of transplantation. One limited bronchial dehiscence occurred; the incidence of postoperative bronchial stenosis was identical in both cohorts; one patient died in each group. In conclusion, no increased morbidity or mortality could be found following lung transplantation with regular preoperative administration of prednisolone up to 0.3 mg/kg/day. Thus, patients who cannot be weaned from their steroid medication but who otherwise are acceptable candidates should not be excluded from lung transplantation. PMID- 1424877 TI - Safety of interventional rigid bronchoscopy using intravenous anesthesia and spontaneous assisted ventilation. A prospective study. AB - STUDY OBJECTIVE: To investigate the safety of total intravenous anesthesia and spontaneous assisted ventilation during interventional rigid bronchoscopy (IRB). DESIGN: Prospective, noncomparative study. SETTING: A university hospital thoracic endoscopy and laser center. PATIENTS: Eighty-three patients underwent a total of 124 procedures (including Nd:Yag laser therapy, stent insertions, transbronchial biopsies/bronchoalveolar lavages (TBB/BALs) in transplant patients and others). Results of preanesthesia consultation, endoscopic and anesthesia intervention, perioperative complications, and time spent in recovery room were recorded prospectively. RESULTS: Respiratory complications occurred in 22 procedures (18 percent) and included severe intraoperative or postoperative oxyhemoglobin desaturations (19 cases), bronchospasms/laryngospasms (two cases), and one recurrent pneumothorax. These complications were mostly related to the endobronchial surgical procedure. Respiratory complications occurred more frequently in patients with American Society of Anesthesiologists (ASA) 3 and 4 status (p < 0.005) and in patients with a karnofsky Performance Scale (KPS) below 70 (p < 0.05). No cardiac complications were noted, although 13 patients had significant underlying heart disease. Propofol was used in 121 procedures. Etomidate was used 15 times for induction and three times for both induction and maintenance in patients with ASA status 4 or low blood pressure before induction. CONCLUSION: Total intravenous anesthesia and spontaneous assisted ventilation is a well-suited technique for IRB. Severe hypoxemia, however, may occur in approximately 15 percent of patients. This complication is usually related to the procedure itself and is easy to reverse. Propofol is well tolerated in the majority of patients but it must be used with care in patients with poor functional or cardiovascular status. PMID- 1424878 TI - Effects of the implementation of a smoke-free policy in a medical center. AB - The implementation of a smoke-free policy in this medical center was associated with a decrease in the prevalence of regular cigarette smoking from 16.7 percent to 13.8 percent and a smoking cessation rate of 22.5 percent among regular smokers over the 2 1/2 years since the policy was announced. This decrease in prevalence is the result of both smoking cessation among existing employees and less frequent regular smoking among new employees. At two-year follow-up, the policy was overwhelmingly endorsed by medical center staff overall but was viewed less favorably by those who continued to smoke. Nevertheless, over the 2 1/2 years, many of these smokers have been in the action stage of cessation (37.1 percent made a serious attempt to stop smoking, 20.7 percent had used nicotine polacrilex in a smoking-cessation effort, and 13.8 percent had attended a formal cessation program). The implementation of a smoke-free policy has made a significant contribution toward providing a healthful work environment and toward encouraging nonsmoking behavior in staff and patients. PMID- 1424879 TI - Unimodal distribution of bronchial hyperresponsiveness to methacholine in asthmatic patients. AB - Distribution of bronchial hyperresponsiveness to methacholine was assessed in 791 consecutive patients who were referred to the outpatient clinic of the pulmonary department due to asthmatic or persistent lower airway symptoms. Bronchial asthma was diagnosed in 319 patients. Clinical sensitivity of methacholine challenge for the disease was 89 percent and specificity, 76 percent. The degree of bronchial hyperresponsiveness in the entire group of asthmatic patients was unimodally log normal distributed. Of the 82 patients with allergic rhinitis without concurrent asthma, 27 percent had bronchial hyperresponsiveness, but of a markedly lesser degree than in the hyperresponsive asthmatic patients. In 49 patients with chronic bronchitis, 22 percent had hyperresponsiveness. The present data indicate that the degree of bronchial hyperresponsiveness in asthmatic patients is unimodally distributed, supporting the view that both genetic and environmental factors have an impact upon its development. Although the degree of bronchial hyperresponsiveness in asthma is more pronounced than in allergic rhinitis or in chronic bronchitis, a marked overlap exists. PMID- 1424880 TI - Formoterol suspension aerosol. Comparison with formoterol solution aerosol for 12 weeks in asthmatic patients. AB - Formoterol solution aerosol has proved to be a fast and long-acting beta 2 sympathicomimetic drug in many clinical trials. The physical stability, however, was such that storage needed to be at 4 degrees C to 8 degrees C before first use; afterwards, the aerosol could be used for another three months at room temperature. To improve the stability, new ways have been investigated to formulate ann aerosol with improved shelf life and thus more convenient storage conditions, which was reached with a formoterol suspension aerosol. Equivalent single doses between the two formulations revealed no differences in onset or duration of action. In a double-blind, randomized parallel group multicenter study, organized in the Netherlands, 186 patients with stable asthma and reversible airway obstruction were treated either with one puff of 12 micrograms twice daily of formoterol metered dose inhaler (MDI) supension (SP) or a same dose of solution (SL) aerosol for 12 weeks to study the efficacy and tolerability of both presentations after a longer period of use. The following criteria of effectiveness were used: the FEV1 values on the mornings of the control days at 0, +4, +8, and + 12 weeks, the peak flow values (PEF) in the mornings and in the evenings before, and 1/2 to 1 h after treatment, the number of asthma attacks at night and during the day, the number of extra puffs at night and during day, and the subjective impression of patients and investigator. RESULT: No statistically significant differences between the two formoterol preparations were found. There was no indication of tachyphylaxis. CONCLUSION: The results are consistent with the hypothesis that the biologic effects of formoterol when delivered from MDI containing the two different formulations of the drug are equivalent. PMID- 1424882 TI - Who should perform thoracoscopy? PMID- 1424881 TI - Pathogenesis of the lung in restrictive defects of Klinefelter's syndrome. AB - Patients with Klinefelter's syndrome show a high incidence of restrictive lung defects, the pathogenesis of which is not clear yet. We investigated the respiratory muscle force (PImax) and lung compliance in 13 patients with Klinefelter's syndrome who had not been receiving hormonal therapy for at least one year prior to being studied. Eleven were smokers and two were nonsmokers. None showed abnormalities of the chest wall. Five had normal lung volumes and eight showed a restrictive defect (TLC < 80 percent, VC < 85 percent, FEV1/FVC percent within normal values); DCOSB and arterial blood gases were within normal limits. PImax was similar in restricted (-115.9 +/- 26.7 cm H2O) and not restricted patients (-115.4 +/- 20.3 cm H2O), all within reference values. Lung compliance, however, was significantly decreased in the four patients studied (0.13 +/- 0.08 cm H2O-1) compared with five normal control subjects (0.29 +/- 0.05 cm H2O-1). We conclude that the likely cause of the lung restriction is a decrease of compliance of the lung matrix, probably related to the absence of testosterone. PMID- 1424883 TI - Who should perform thoracoscopy? PMID- 1424884 TI - Who should perform thoracoscopy? PMID- 1424885 TI - Who should perform thoracoscopy? PMID- 1424886 TI - Who should perform thoracoscopy? PMID- 1424887 TI - Who should perform thoracoscopy? PMID- 1424888 TI - Who should perform thoracoscopy? PMID- 1424889 TI - Effects of inverse ratio ventilation on cardiorespiratory parameters in severe respiratory failure. AB - Inverse ratio ventilation, with prolonged inspiratory times, appears to improve gas exchange and arterial oxygenation in patients with severe respiratory failure; however, in previous studies, pressure-controlled inverse ratio ventilation (PC-IRV), which uses a rapidly decelerating inspiratory flow pattern, was compared to conventional volume-controlled ventilation, which uses a constant inspiratory flow rate. Pressure-controlled ventilation (PCV), with a decelerating inspiratory flow pattern and conventional inspiratory-to-expiratory (I/E) ratios, also has been shown to produce improvement in PaO2 when compared to volume controlled ventilation. It therefore is unknown if the potentially beneficial effects of PC-IRV are due to the reversal of I/E ratios or to the use of the rapidly decelerating inspiratory flow pattern. In order to investigate this issue, cardiorespiratory values were measured in ten patients with severe respiratory failure ventilated first with PCV, then PC-IRV, and finally with a second period of PCV. Tidal volume, respiratory rate, end-expiratory pressure, and fraction of oxygen in inspired gas (FIO2) were maintained at the same value for both ventilatory modalities. The PC-IRV was associated with significant increases in PaO2, arterial pH, and mean airway pressure. Significant decreases in pulmonary shunt fraction, PaCO2, and cardiac index were found with PC-IRV. No significant changes in tissue oxygen delivery or consumption occurred with either PCV or PC-IRV. These results demonstrate that inversion of conventional I/E ratios produces no significant improvement in the overall cardiorespiratory profile of critically ill patients. This study also suggests that the clinical utility of PC-IRV is limited except in the setting of the adult respiratory distress syndrome with hypoxemia or hypercapnia refractory to other therapeutic options. PMID- 1424890 TI - Pneumonia due to Haemophilus influenzae among mechanically ventilated patients. Incidence, outcome, and risk factors. AB - Incidence and potential risk factors for pneumonia due to Haemophilus influenzae in adults treated with mechanical ventilation in a medical-surgical ICU were investigated. Diagnosis was established in 91 episodes and H influenzae was isolated in 20 of them. Mean onset of ventilator-associated pneumonia (VAP) due to H influenzae was 10.8 days after intubation. Six patients with H influenzae VAP died in the ICU. Of 13 risk factors for developing VAP due to H influenzae, an absence of prior antibiotic treatment was the only variable which had statistical significance (p < 0.001). In these mechanically ventilated patients, Haemophilus influenzae was a common causative agent for VAP, frequently associated with Gram-positive cocci. Episodes of H influenzae VAP were associated with a lower mortality compared with other etiologies. The epidemiologic and clinical findings indicate that patients without a prior antimicrobial treatment have increased susceptibility to infections of the airway by H influenzae. PMID- 1424891 TI - Assessing hypermetabolism and hypometabolism in the postoperative critically ill patient. AB - To determine whether a patient is hypermetabolic or hypometabolic, measured resting energy expenditure is compared with estimated (or predicted) energy expenditure. The latter is calculated using equations derived from measurements made in groups of healthy individuals. Body weight or body surface area are among the variables used in these equations. Yet, in critically ill patients, body weight often rises because of fluid resuscitation. This study examined the differences between using preoperative, postoperative, and ideal body weights on the determination of hypermetabolism and hypometabolism in mechanically ventilated, critically ill patients. When the elevated postoperative weights were used instead of the preoperative ones to predict energy expenditure, the degree of hypermetabolism was underestimated. Subtracting the weight of the cumulative net fluid balance from the postoperative weight was found to accurately reflect preoperative weight. The influence of various predictive equations on the magnitude of hypermetabolism was also explored. In conclusion, it is important, when determining hypermetabolism or hypometabolism, to consider the influence of the specific predictive equation used and the effect of resuscitation fluid. PMID- 1424892 TI - The Organ Donation Committee. An ethically responsible approach to increasing the organ donation rate. PMID- 1424893 TI - Thrombocytopenia, cutaneous necrosis, and gangrene of the upper and lower extremities in a 35-year-old man. PMID- 1424894 TI - Acute respiratory failure associated with a motor vehicle accident. PMID- 1424895 TI - Anomalous systemic arterial supply to normal basilar segments of the lower lobe of the left lung. AB - A 38-year-old man with an anomalous systemic arterial supply from the descending thoracic aorta to the normal basilar segments of the left lower lobe experienced symptoms of progressive exertional dyspnea. Although the pulmonary parenchyma was normal, there was no pulmonary arterial supply to the basilar segments of the left lower lobe. Left lower lobectomy was performed because of worsening left-to left shunt. Aortography and pulmonary arteriography form the cornerstone for diagnosis, but a less invasive diagnostic method with less patient suffering is high-resolution computed tomography, which might replace bronchography for accurate evaluation of the distribution and patency of the bronchial tree and delineation of the characteristic "Medusa's hair"-like anomalous vascular supply penetrating into the nearly normal pulmonary parenchyma. PMID- 1424896 TI - Transmission of Legionella by respiratory equipment and aerosol generating devices. PMID- 1424897 TI - Experimental polyacrylamide-induced acute injury in rat lung. AB - We recently reported the first case of accidental aspiration of polyacrylamide occurring in a 26-year-old man. The patient developed severe airway obstruction and parenchymal lung damage and died. Autopsy revealed numerous polyacrylamide particles in his lungs, as well as extensive bronchiolar and alveolar damage. Gas chromatographic and mass spectrometric assessment of the lung tissue failed to reveal polyacrylamide activity, although assessment of the suspending solvent of the polyacrylamide showed a pattern characteristic of an aliphatic hydrocarbon mixture with a prominent dodecane peak. This experimental study was performed to determine the nature and extent of damage to rat bronchial and alveolar epithelia following endotracheal instillation of polyacrylamide, hydrocarbon mixture (petroleum distillate), dodecane (C12H26), or normal saline. The rat lungs were examined grossly and microscopically 10 min and 24, 72, and 96 h after endotracheal instillation, following inflation and fixation with 10 percent buffered formaldehyde. Gross examination revealed congested, mottled visceral pleural surfaces in the rats treated with polyacrylamide and dodecane. There were no pleural exudates or effusions. Microscopically, vascular engorgement, bronchiolitis, and focal pneumonia were observed. Vascular engorgement was most pronounced at 72 to 96 h in rat lungs treated with polyacrylamide and dodecane and was moderate at 24 h in rats treated with petroleum distillate. Focal organizing pneumonia was marked at 96 h in rats treated with petroleum distillate, at 72 h in those treated with polyacrylamide, and at 24 h in those treated with dodecane. The saline-treated control animals showed no change. Our findings suggest that polyacrylamide, dodecane, and petroleum distillate are strong irritants to the airways. However, a direct obstructive/mechanical effect of the polyacrylamide upon the airway has not been excluded. Airway exposure to polyacrylamide may result in lung injury secondary to the polyacrylamide itself, its suspending agents, or both. PMID- 1424898 TI - Propylthiouracil-induced hypersensitivity vasculitis presenting as respiratory failure. AB - Hypersensitivity vasculitis associated with propylthiouracil therapy is a well documented clinical entity. Although any organ system may be involved, it is most unusual for pulmonary manifestations to be the cardinal presenting features. We report a 72-year-old woman presenting with respiratory failure and hemoptysis following initiation of propylthiouracil therapy for Graves' disease. She had cutaneous stigmata of hypersensitivity vasculitis and diffuse pulmonary infiltrates. The infiltrates improved dramatically after discontinuation of the propylthiouracil therapy and initiation of intravenous corticosteroid therapy. PMID- 1424899 TI - Pulmonary amyloidoma. Histologic proof yielded by transthoracic coaxial fine needle biopsy. AB - Nodular pulmonary amyloidosis was diagnosed by percutaneous transthoracic fine needle biopsy specimen in an 88-year-old woman. Congo red staining should be performed whenever band-like hyalinized material is obtained on aspiration of a solitary nodule. Dense calcifications can occur in pulmonary amyloidomas. In selected cases, fine needle biopsy appears to be preferable to transbronchial forceps biopsy since the risk of a possibly life-threatening pulmonary hemorrhage may be lower. PMID- 1424900 TI - Thrombosed prosthetic valve in tricuspid position. Successful therapy with intravenous streptokinase. AB - The successful use of streptokinase therapy in a child with chronic thrombosis of a prosthetic valve (Carbomedics) in the tricuspid position is presented. PMID- 1424901 TI - Isolation of Legionella pneumophila serogroup 5 from empyema following esophageal perforation. Source of the organism and mode of transmission. AB - A patient undergoing esophageal dilatation for carcinoma of the esophagus suffered esophageal perforation and development of an empyema. Culture of pleural fluid yielded multiple organisms, including Legionella pneumophila serogroup 5. Epidemiologic investigation showed that the source of L pneumophila was a tap used by the nursing personnel to fill patients' water pitchers. Whole-cell restriction endonuclease analysis of DNA from the clinical and environmental isolates of L pneumophila serogroup 5 yielded identical patterns. Our findings suggest that L pneumophila was acquired by the patient at least 12 h prior to the procedure causing the esophageal perforation and empyema, suggesting that the organism can persist in an infectious form in the upper aerodigestive tract. PMID- 1424902 TI - Tuberculosis of the thymus. AB - Tuberculosis is increasing in prevalence in North America, mainly due to HIV infection. We describe an unusual case of TB of the thymus in a HIV sero-negative Filipino immigrant who preoperatively was thought to have a thymoma. We describe the clinical, radiologic and pathologic findings and review the literature on TB of the thymus. PMID- 1424903 TI - Christmas candy maker's asthma. IgG4-mediated pectin allergy. AB - We evaluated a 29-year-old candy maker with no history of asthma who developed asthma after exposure to pectin, a compound manufactured from fruits and fruit rinds. Following eight years of employment during which he added pectin to a recipe for Christmas candies, the candymaker developed acute respiratory symptoms. Challenge testing with the pectin mixture caused a 40 percent decrease in FEV1. Skin prick testing was positive to the pectin extract. Total IgE was normal and pectin-specific IgE antibodies were not detected. A strongly positive pectin-specific IgG4 antibody response was present that was not detected in a control serum and could be inhibited by the addition of pectin. Antigen-specific IgG4 should be sought in IgE negative cases of occupational asthma. PMID- 1424904 TI - Pulmonary diffuse amyloidosis and ankylosing spondylitis. A rare association. AB - We report herein the association of primary pulmonary amyloidosis and ankylosing spondylitis. To our knowledge, this rare association has never been reported. This case reemphasizes that not all pulmonary complications that appear in the course of ankylosing spondylitis are related to the seronegative spondyloarthropathy. Primary pulmonary amyloidosis should be considered in patients with interstitial pulmonary disease. PMID- 1424905 TI - Early congestive heart failure due to origin of the right coronary artery from the pulmonary artery. AB - We describe a two-month-old infant with early congestive heart failure due to anomalous origin of the right coronary artery from the pulmonary artery. The diagnosis was made by two-dimensional and color flow Doppler echocardiography, confirmed by angiocardiography, and the case was successfully corrected at surgery. As opposed to the more frequent anomalous origin of the left coronary artery from the pulmonary trunk, this anomaly generally does not cause any typical clinical finding, often becoming an autoptic or surgical surprise after infancy or in adult age. PMID- 1424906 TI - Empyema following percutaneous catheter drainage of upper abdominal abscess. AB - Percutaneous catheter drainage is a standard therapy for management of selected intra-abdominal abscesses. We describe three patients in whom this technique caused complicated thoracic empyemas. All patients required thoracotomy for decortication despite initial thoracostomy tube drainage. In each case, the percutaneously placed drainage catheter was found traversing the costophrenic angle, leading to direct communication between the pleural space and the abscess cavity. Review of the anatomic relationships of the inferior pleural margin to the lower ribs may help prevent this technical error. PMID- 1424907 TI - Extensive diffuse pulmonary ossification. AB - Diffuse lung injury can either heal normally or progress to fibrosis. Calcification in the setting of fibrosis is common. The appearance of mature woven bone is not. We report a patient with extensive diffuse pulmonary ossification and discuss some of the theories relating to the development of this phenomenon. PMID- 1424908 TI - Ultrastructurally normal and motile spermatozoa in a fertile man with Kartagener's syndrome. AB - The findings in a 40-year-old man with Kartagener's triad (sinusitis, bronchiectasis, and situs inversus) and corrected transposition of the great vessels are presented. Electron microscopy revealed normal ultrastructure of the axoneme in both respiratory cilia and sperm tails. Light microscopic evaluation of the spermatozoa showed 50 percent motility, suggesting normal fertility. This assumption is confirmed, as the patient has two children. We suggest that an abnormal, uncoordinated motility pattern of the ultrastructurally normal respiratory cilia results in improper mucociliary clearance. This coordination is not needed in swimming spermatozoa, which could explain the apparent paradox between bronchopulmonary symptoms and normal fertility in our patient. PMID- 1424909 TI - Dynamic left ventricular outflow obstruction related to atrial fibrillation. AB - A 48-year-old male patient underwent mitral annuloplasty for severe mitral regurgitation secondary to myxomatous degeneration of the mitral valve, with ruptured chordae. Intraoperative transesophageal echocardiography showed satisfactory repair. The patient developed postoperative atrial fibrillation and clinical and echocardiographic evidence of left ventricular outflow obstruction. Following conversion to sinus rhythm, the evidence for left ventricular outflow obstruction markedly improved. We suggest that postoperative atrial fibrillation may precipitate dynamic left ventricular outflow obstruction following mitral annuloplasty. PMID- 1424910 TI - Successful medical therapy of Rhodococcus equi pneumonia in a patient with HIV infection. AB - A 34-year-old HIV-infected man was successfully treated with antimicrobial therapy alone for Rhodococcus equi pneumonia and has survived longer than six months. In the current literature, only two of seven HIV-infected patients so treated have survived as long as six months. Based on our experience and the available literature, it seems reasonable to treat HIV-infected patients with R equi pneumonia who do not require surgical intervention with prolonged intravenous therapy followed by long-term oral therapy with at least two effective antibiotics. The optimal choice and duration of antibiotic therapy need to be determined. PMID- 1424911 TI - Clearance of theophylline by hemodialysis in one patient with chronic renal failure. AB - The clearance of theophylline by hemodialysis was determined in one patient who had polycystic kidney with chronic renal failure and bronchial asthma. The serum levels of theophylline were determined by enzymatic immunoassay on two consecutive days, once on a dialysis day and again on a nondialysis day. Clearance of theophylline by hemodialysis was 119 ml/min, and the extraction efficiency was 0.56. The elimination half-life of theophylline shortened from 5.7 h to 1.6 h during hemodialysis. The dialysis rate constant (Kd) was 0.32/h, and 79 percent of the total body store of the drug was removed during a 4-h dialysis. Patients receiving theophylline who are maintained on hemodialysis should be closely monitored for bronchospasm during and after the hemodialysis procedure. Measurement of serum concentrations of theophylline should be employed to facilitate increases in dosage during hemodialysis. PMID- 1424912 TI - Imaging of multiple coronary artery fistulas to right ventricle by transthoracic and transesophageal echocardiography. AB - A 20-year-old woman presented with extremely rare multiple coronary artery fistulas with left circumflex and right coronary arteries as the feeding vessels and two distinct sites of drainage into the posterior wall of the right ventricle near the apex in close proximity. The large left fistula was well depicted by transthoracic echocardiography, whereas the transesophageal approach better delineated part of the smaller right fistula. PMID- 1424913 TI - Positive pressure mechanical ventilation augments left ventricular function in acute mitral regurgitation. AB - Although inconclusively established, positive pressure ventilation may augment cardiac function in congestive cardiomyopathies. We report a patient with acute mitral regurgitation who experienced enhanced myocardial performance and resolution of large pulmonary artery v waves during mechanical ventilation. This observation supports the existence of a cardiac booster effect from positive pressure ventilation. PMID- 1424914 TI - The advantage of d-sotalol over dl-sotalol in a patient with ventricular arrhythmias and comorbid bronchospasm. AB - The anti-arrhythmic agent sotalol, a racemic mixture of d- and l-isomers, has inherent beta-adrenoceptor blocking activity due to the l-isomer form. For patients with contraindications to beta-adrenoreceptor blockade, dl-sotalol has potentially untoward effects that may limit its usefulness. The case of a man with resistant life-threatening ventricular arrhythmias who responded favorably to dl-sotalol, but developed worsening of underlying bronchospastic lung disease, is presented. A change in therapy to the d-isomer form of sotalol, d-sotalol, was effective in suppressing his ventricular arrhythmias without further aggravation of bronchospasm. PMID- 1424915 TI - Right coronary artery-right atrium fistula in primary angiosarcoma of the heart. AB - We report a case of angiosarcoma of the heart, manifested as a continuous murmur. Right coronary arteriography disclosed a paracardiac mass with fistulas from the coronary vessel to the right atrium. Histologic study revealed this to be an angiosarcoma with sinusoidal pattern. To our knowledge, this is the first case of this kind of cardiac tumor presenting as a fistula from a coronary artery to the right atrium. PMID- 1424916 TI - Diagnostic value of mononuclear cell infiltration in subpleural adipose tissue. PMID- 1424917 TI - Traumatic coronary artery-atrioventricular fistula. A 26-year follow-up with application of transesophageal echocardiography. PMID- 1424918 TI - Thromboembolism associated with acquired immunodeficiency syndrome. PMID- 1424919 TI - Pulmonary intubation with nasogastric tubes. PMID- 1424920 TI - Inadvertent pericardiacophrenic vein catheterization. PMID- 1424922 TI - Variability in aerosol output of the DeVilbiss 646 jet nebulizer. PMID- 1424921 TI - Diagnosis of tuberculous pleural effusion by the detection of tuberculostearic acid in pleural aspirates. PMID- 1424923 TI - Volume adjustment of maximal expiratory flow rates of flow-volume loops. PMID- 1424924 TI - Chronic cough caused by endobronchial sutures. PMID- 1424925 TI - Bronchoscopy in North America. The ACCP survey. PMID- 1424926 TI - Bronchoscopy in North America. The ACCP survey. PMID- 1424927 TI - Bronchoscopy in North America. The ACCP survey. PMID- 1424928 TI - International Consensus Conference: clinical investigation of ventilator associated pneumonia. Introduction. PMID- 1424929 TI - Patient selection for clinical investigation of ventilator-associated pneumonia. Criteria for evaluating diagnostic techniques. PMID- 1424930 TI - The standardization of bronchoscopic techniques for ventilator-associated pneumonia. PMID- 1424931 TI - Guidelines for reading and interpreting chest radiographs in patients receiving mechanical ventilation. PMID- 1424932 TI - The standardization of criteria for processing and interpreting laboratory specimens in patients with suspected ventilator-associated pneumonia. PMID- 1424933 TI - Methodology for clinical investigation of ventilator-associated pneumonia. Epidemiology and therapeutic intervention. PMID- 1424934 TI - Pathogenesis and management of cardiogenic shock and postoperative shock. Introduction. PMID- 1424935 TI - Pathogenesis of low output in right ventricular myocardial infarction. PMID- 1424936 TI - Nonpharmacologic management of cardiac arrest and cardiogenic shock. PMID- 1424937 TI - Hemodynamic and oxygen transport patterns for outcome prediction, therapeutic goals, and clinical algorithms to improve outcome. Feasibility of artificial intelligence to customize algorithms. AB - A generalized decision tree or clinical algorithm for treatment of high-risk elective surgical patients was developed from a physiologic model based on empirical data. First, a large data bank was used to do the following: (1) describe temporal hemodynamic and oxygen transport patterns that interrelate cardiac, pulmonary, and tissue perfusion functions in survivors and nonsurvivors; (2) define optimal therapeutic goals based on the supranormal oxygen transport values of high-risk postoperative survivors; (3) compare the relative effectiveness of alternative therapies in a wide variety of clinical and physiologic conditions; and (4) to develop criteria for titration of therapy to the endpoints of the supranormal optimal goals using cardiac index (CI), oxygen delivery (DO2), and oxygen consumption (VO2) as proxy outcome measures. Second, a general purpose algorithm was generated from these data and tested in preoperatively randomized clinical trials of high-risk surgical patients. Improved outcome was demonstrated with this generalized algorithm. The concept that the supranormal values represent compensations that have survival value has been corroborated by several other groups. We now propose a unique approach to refine the generalized algorithm to develop customized algorithms and individualized decision analysis for each patient's unique problems. The present article describes a preliminary evaluation of the feasibility of artificial intelligence techniques to accomplish individualized algorithms that may further improve patient care and outcome. PMID- 1424938 TI - Pathogenesis and management of acute heart failure and cardiogenic shock: role of inotropic therapy. AB - Patients with acute heart failure or cardiogenic shock following myocardial infarction have a high mortality. The first priority is to salvage any remaining viable myocardium, either by thrombolytic agents or, if necessary, by coronary angioplasty. A mechanical cause for the heart failure or shock needs to be excluded. Thereafter, the optimal therapeutic regimen needs to be chosen on the basis of each patient's hemodynamic profile. Patients can be broadly classified into three groups: (1) patients with a high left ventricular filling pressure (> 18 mm Hg) and a cardiac index < 2.2 L/min/m2 but systolic arterial pressure > 100 mm Hg; (2) patients with a systolic arterial pressure < 90 mm Hg, left ventricular filling pressure > 18 mm Hg, and cardiac index < 2.2 L/min/m2; and (3) patients with an elevated right ventricular filling pressure (> 10 mm Hg) and cardiac index < 2.2 L/min/m2 and a systolic arterial pressure < 100 mm Hg. Patients in the first subset usually require the use of vasodilator therapy and/or dobutamine. The choice of inotropic agent in patients in the second hemodynamic subset depends on the degree of systemic hypotension; dopamine is usually preferred initially because it increases arterial pressure in addition to improving cardiac output. Once the systemic blood pressure has been stabilized, dobutamine can be substituted for superior augmentation of cardiac output and its additional beneficial effects on the left ventricular filling pressure. Norepinephrine may be indicated in cases of severe systemic hypotension. Patients in hemodynamic subset 3, ie, right ventricular infarction, are treated with volume expansion and dobutamine. Use of nonpharmacologic means of circulatory support, eg, intra-aortic balloon pump or left ventricular assist device may also be required in any of these subsets. PMID- 1424939 TI - Cognitive therapy with young children. AB - This paper discusses the common cognitive features characterizing children's most frequently referred problems, with an emphasis on the difficulties' prevalence, gender ratio, and family incidence. The efficacy of cognitive treatments is examined in terms of dropping-out, regression, and generalization. In view of Piaget's notion on the concrete thinking of children, it is suggested that cognitive therapy be adopted for children by translating abstract, holistic concepts into concrete examples and by relating to day-to-day events which children can use, relate to and understand. Two cases studies are presented to illustrate the cognitive therapeutic process with young children. PMID- 1424940 TI - PTSD in physically and sexually abused psychiatrically hospitalized children. AB - The history of sexual and physical abuse and the diagnosis of PTSD were examined in 98 psychiatrically hospitalized children. Relative to past studies, there was an increased incidence of abuse and of prevalence of PTSD. Specific instruments for assessing abuse and PTSD are suggested. PMID- 1424942 TI - The relationship of suicidality and psychiatric diagnosis in hospitalized pre adolescent children. AB - Two structured interview measures of suicidal behavior were administered to 43 child psychiatric inpatients between the ages of 7 and 11 and their parents. DSM III-R diagnoses were assigned to the children, with twenty-six Axis I and Axis II diagnostic categories represented. Generally, the interview measures of suicidal behavior were found to be unrelated to psychiatric diagnosis. The results suggest that to better understand pre-adolescent suicidal behaviors, it may be more useful to examine associations between these behaviors and the biopsychosocial dimensions that underlie the diagnostic categories. PMID- 1424941 TI - Emotional disorders in learning disabled adolescents. AB - We retrospectively reviewed patients discharged from the psychiatric inpatient adolescent service and correlated neuropsychological subtypes with the patient's psychiatric diagnoses. Depressed learning disabled patients had visual memory and processing deficits. Conduct or behaviorally disordered patients had expressive language deficits. Learning disability subtypes may affect psychotherapy and therefore should be known when planning psychotherapy. PMID- 1424943 TI - Are children who steal different from those who are aggressive? AB - Data on 2181 children referred to a child psychiatry service were analyzed to determine if there were specific correlates for aggressive behavior and for stealing behavior. Compared with stealers, aggressive children tended to be younger and more immature males, and to come from stressed families with a history of mental illness. These findings support the notion that there are biological and reactive components to aggression. PMID- 1424944 TI - Characteristics of effective, harm-free environments for children in out-of-home care. AB - The history of out-of-home care is replete with documented examples of abusive and neglectful practices. Some scholars express concern that out-of-home care is de facto abusive. Certain elements, however, can foster effective and harm-free out-of-home care, such as caregiver support, a model of care, a focus on positive behavior, a consumer orientation, training, program evaluation, and an internal program audit. These elements work together to increase program effectiveness and reduce negative outcomes such as staff burnout. Furthermore, programs that use these elements can be cost efficient. PMID- 1424945 TI - Policy and practice for response to foster families when child abuse or neglect is reported. AB - For reasons discussed in this article, it is in the nature of family foster care that allegations of abuse and/or neglect in foster homes will arise. How an agency acts before, during, and after these eventualities has long-lasting implications for the well-being of foster children and of foster parents and their own children, as well as for foster home recruitment. PMID- 1424946 TI - Integrating special-needs adoption with residential treatment. AB - Current estimates indicate that 76% of Iowa children whose parents' rights have been terminated and who are listed on the adoption exchange are older children with emotional/behavioral disabilities. Residential treatment can play a significant role in preparing difficult-to-place children (e.g., seven- to 14 year-olds with moderate to severe emotional or behavioral problems) for adoptive placement [Powers and Powell 1982]. The SATT model offers the opportunity to effectively manage the risks in adoptive placement for these children. PMID- 1424947 TI - Gay and no place to go: assessing the needs of gay and lesbian adolescents in out of-home care settings. AB - Gay and lesbian adolescents, whether self-declared or in the throes of sexual identity struggles, are and have been in out-of-home care settings. Their placements are often negative experiences because their feelings of difference are frequently aggravated by the attitudes of those around them, including other children and some staff members. This article discusses factors that can help make placement a positive experience for these youths. PMID- 1424948 TI - Cognitive-behavioral-expressive interventions with aggressive and resistant youths. AB - Research into the nature of aggressive behavior in youths has demonstrated that these youths are often the victims of abuse, exhibit aggressive behavior in early childhood, and remain aggressive into young adulthood. The treatment approach described in this article is a modification of Monahan's [1981] model of the prediction of violent behavior and the anger-management approach of Novaco [1985], and integrates the developmental models of Piaget [1963] and Erikson [1959]. The program is a combination of cognitive, behavioral, and expressive therapies and is targeted to the reduction of dysfunctional cognitive, affective, behavioral, and problem-solving patterns of aggressive youths. As referrals of such aggressive clients are often involuntary, interventions with unwilling and resistant clients are also presented. PMID- 1424949 TI - Fostering homeless children and their parents too: the emergence of whole-family foster care. AB - Children should not be placed in out-of-home care simply because their families lack the means to provide for their basic needs, yet this practice continues nationwide. A new program based in St. Paul, MN, gives county social service departments the placement option of whole-family foster care. The target population is adult parents and minor children without stable residences, where the children are at risk of placement in out-of-home care. Although the parents and children may have special needs, there are no safety risks that would necessitate separating children and parents. The program's design is described and policy questions discussed. PMID- 1424950 TI - Junior life skills: an innovation for latency-age children in out-of-home care. AB - Children age seven to 13 in out-of-home care should be given instruction in basic life skills, just as their older counterparts are prepared for independent living. One program that provides such instruction is detailed here. PMID- 1424951 TI - Different effects of estradiol and progesterone on the secretion of calcitonin in ovariectomized rats. AB - The basal and calcium-stimulated secretion of calcitonin (CT) was studied in ovarian steroid hormone-injected ovariectomized (Ovx) rats. Ovx rats were injected subcutaneously once daily for 3 days with estradiol benzoate (EB, 25 micrograms/kg), progesterone (P, 50 mg/kg), EB and P, or sesame oil. All rats were then infused with 10% CaCl2 at a rate of 2 ml/h for 30 min via a femoral vein catheter connected to a peristaltic pump. Blood samples (0.5 ml each) were collected from the right jugular vein at 0, 30, 60, and 120 min. The concentration of plasma CT was measured by a human calcitonin radioimmunoassay. The level of plasma calcium was determined by an automatic calcium analyzer. The basal plasma CT level was significantly higher (p less than 0.01) in Ovx rats injected with P and the combination of EB and P than that in rats injected with oil. Ovarian steroid hormones injection did not alter plasma CT concentrations at 30 and 60 min following calcium infusion when compared with those injected with oil. Ninety min following termination of calcium infusion, plasma CT levels were higher (p less than 0.01) in EB- and both EB and P-injected Ovx rats than in oil injected animals. EB or P injection had no effect on the basal plasma calcium concentration. Plasma calcium concentration at 30 min following calcium challenge was higher (p less than 0.01) in EB-injected Ovx rats than in control (oil injected). These results suggest that (1) progesterone stimulates the basal secretion of CT, and (2) CT secretion in response to calcium infusion is stimulated in estradiol-treated ovariectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424952 TI - Preliminary studies of duration and intensity of ultrasonic treatments on fracture repair. AB - Bone formation of fractured fibulae stimulated by ultrasound was evaluated with roentgenography and fluorochromes labelling. The fibulae of male New Zealand rabbits were fractured to create a 3 mm-gap. Ultrasounds at 0.5 or 1.0 W/cm2 were applied for various durations, 5, 15, and 25 min/day for 4 weeks. Ultrasonic treatments at 0.5 W/cm2, 1.5 MHz significantly accelerated bone formation at the fracture site for all durations, whereas the higher intensity at 1.0 W/cm2 suppressed the bone formation of the treated fractured fibula. Ultrasounds at 0.5 W/cm2 were stimulatory to fracture repair, if given for 15 min/day, and were recommended for future clinical trials. However, ultrasounds at the intensity of 1.0 W/cm2 were deleterious to the treated fracture and not recommended for clinical trials. PMID- 1424953 TI - Ultrasonic effect on fracture repair and prostaglandin E2 production. AB - Ultrasound has been recently recognized of its potential in promoting fracture healing. However, its effects on bone healing remain unclarified. The present study was initiated to compare the effects of frequency on fracture healing and the possible role of endogenous prostaglandin E2 in fracture healing stimulated by ultrasound. Histologic evaluation of callus formation with labelled fluorochromes indicated that the use of ultrasound at 1.5 MHz was most effective in accelerating bone healing. In addition, at this frequency, the endogenous PGE2 level was significantly elevated, which paralleled the accelerated bone healing. It is suggested that bone healing stimulated by ultrasound may be mediated via the production of PGE2. PMID- 1424954 TI - The effects of heavy eccentric contractions on serum creatine kinase levels. AB - Post-exercise serum creatine kinase (CK) has been frequently used to evaluate muscle damage. The purpose of present study was to examine the effects of 45 eccentric contraction on serum creatine kinase levels during laboratory tests. Using a Lido isokinetic dynamometer, thirteen subjects (five distance runners and eight PE students), average age = 24.0 (yrs), height = 172.5 (cm), weight = 66.5 (kg), and percent body fat = 15.3 (%), completed 5 and 40 eccentric contractions at speed of 60 degrees C/s and 120 degrees/s, respectively. Blood sample was drawn before and 18, 42, 66, 90 hours after exercise protocol. Result indicated that PE students have a significant increase in serum CK levels post-exercise 18 hours (p less than 0.05) only. Both groups in absolute muscular strength or corrected strength have found non-significant difference (p greater than 0.05). Resulting findings showed that training effect may be an important factor for CK leakage rather than lean body mass. In the light of results, it is seem safe to say that the exercise protocol for distance runners using by this study would not contribute to severe CK elevations in blood. This testing protocol can be recommended as an appropriate test for students and distance runners with similar fitness level. Due to large variations occurred during CK testing, follow-up study should try to establish baseline serum CK level by repeated enzyme tests. PMID- 1424955 TI - Drug effects on the ischemia- and reperfusion-induced arrhythmias in the conscious rats. AB - A simple model of coronary occlusion and reperfusion in conscious rat was used to test the effects of various drugs on the arrhythmias. Blood pressure and ECG were monitored on a Grass polygraph. Intravenous infusion of test agents started before coronary occlusion and continued through the periods of occlusion and reperfusion. The free radical scavengers (allopurinol 12.3 mg/kg, mannitol 33.0 mg/kg, N-2-mercapto-propionyl glycine 8.6 mg/kg and adenosine 10.0 mg/kg), class 1-4 antiarrhythmic drugs (lidocaine 10.2 mg/kg, quinidine 12.3 mg/kg, propranolol 4.9 mg/kg, amiodarone 5.6 mg/kg and verapamil 1.1 mg/kg), aspirin 24.5 mg/kg and benadryl 3.7 mg/kg reduced the incidence of ventricular fibrillation and shortened the duration of arrhythmias during occlusion and reperfusion. Cimetidine 6.9 mg/kg was ineffective to exert the antiarrhythmic action. These results implicate that multiple factors, such as ionic channels (Na, K and Ca), free radicals, arachidonate metabolites and histamine release may play significant roles in genesis of arrhythmias during myocardial ischemia and reperfusion. PMID- 1424956 TI - The treatment of congenital hip dislocation between the ages of 1 and 3. AB - A total of 81 patients (103 hips) with a diagnosis of congenital hip dislocation were reviewed, who had been treated between one and three years of age. All of the patients were initially treated with adhesive band traction prior to non surgical reduction, which was performed under general anesthesia using gentle reduction maneuvers followed by immobilization in plaster. Non-surgical reduction was performed in 69 hips (67%), surgical in the remaining 34 (33%). A total of 91 associated surgical procedures were performed for the treatment of residual subluxation. Average follow-up was 12 years (minimum 5, maximum 19). The clinical results of the non-surgical reductions were excellent in 75% of the cases. Radiographically, 48% are hips which have a normal aspect, while 42% have a moderate degree of residual dysplasia or deformity of the femoral epiphysis and of the acetabulum. Hips that were initially classified as grade III dislocations show fair results. Hips treated non-surgically included 11 cases of avascular necrosis (16%); recovery was adequate. Hips treated surgically included 14 cases of avascular necrosis (30%), which was more accentuated in those hips that had initially been treated elsewhere, and in those classified as grade III. The clinical and radiographic results obtained for the hips treated surgically demonstrate poor results in 17% of the cases (6 out of 34), as a consequence of types III and IV osteochondrosis. It may be concluded that in this age group congenital hip dislocation is best treated by non-surgical reduction, possibly followed by surgery of the femur and acetabulum. Surgical reduction was only indicated when conservative methods failed. PMID- 1424957 TI - Treatment of the sequelae of septic osteoarthritis of the hip during pediatric age. AB - A total of 69 cases (73 hips) of the sequelae of septic osteoarthritis of the hip are studied. The sequelae are classified based on whether or not the femoral epiphysis is present, and on stability of the joint according to Hunka (1982). Three of the hips were treated non-surgically. All of the others were submitted to from a minimum of 2 to maximum of 5 operations with the purpose of re establishing joint relationships. The results were: good: 50 hips (72.5%); fair 12 (17.4%); poor: 11 (16%). The most significant sequelae were hip instability, joint function limitation, and shortening of the limb. PMID- 1424958 TI - Traumatic lesions of the triradiate cartilage. AB - Traumatic lesions of the triradiate cartilage (TC) are a rare occurrence and at a high risk for premature closure with consequent acetabular dysplasia and subdislocation of the femoral epiphysis. Based on their experience (5 cases: 2 type II and 3 type V according to the Salter-Harris classification system) and on the literature, the authors affirm that the most significant prognostic factors of this acetabular dysplasia are the age of the patient (under 10 years) and the type of lesion (Salter-Harris type V). After emphasizing how difficult it is to make a diagnosis (which is often made later on), the authors take into consideration some traumatic lesions of the pelvis and hip which by means of different mechanisms may influence the TC: fracture of the ilio- and ischio-pubic branches, fracture of the neck and detachment of the proximal epiphysis of the femur, traumatic dislocation of the hip. These lesions are often the only indirect sign of lesion, even severe ones, of the TC, and require accurate diagnostic testing (ultrasonography, CAT, MRI). PMID- 1424960 TI - Arthroscopic arthrolysis of intra-articular knee stiffness. AB - The authors report 15 cases of intra-articular knee stiffness treated by arthroscopic arthrolysis with or without section of the alar ligaments. The advantages to using this type of treatment as compared to mobilization in narcosis or arthrotomic arthrolysis are emphasized. PMID- 1424959 TI - Primary osteonecrosis in the knee evaluated by histopathology and specimen scintimetry related to clinical radiography, scintimetry and MR. AB - Arthroplasty for primary osteonecrosis of the femoral condyle of the knee was performed in 5 patients and the resected pieces of bone were studied histologically. The patients had been given 99 mm-Tc-MDP preoperatively and the scintimetric uptake in the resected bone pieces was determined. All patients had changes typical for osteonecrosis preoperatively on radiographs and scintimetry. In one case MRI investigation was performed. The histological investigation showed necrotic bone with empty lacunae and fatty degeneration corresponding to the osteonecrosis center. A reparative bone formation, osteoblastic activity, cartilage formation and bands of fibrovascular granulation tissue were observed at the borders to intact bone. The scintimetric uptake of the resected bone pieces showed a high uptake corresponding to the osteonecrosis center. The MR examination showed a well demarcated osteonecrotic region. The findings emphasize the localized nature of the osteonecrosis disease. PMID- 1424961 TI - A method used to evaluate knee osteoarthritis secondary to ligament reconstruction. AB - Serious ligament injuries of the knee always involve early secondary arthritic lesion. Surgical reconstruction of the injured ligaments can partially prevent the degenerative process. Nonetheless, surgical trauma may, in turn, cause articular lesion. The authors suggest and discuss a new method used to evaluate knee osteoarthritis occurring after ligament reconstruction, which may be of use to an objective opinion based on long-term results. What makes this method original is that it is based on a comparison of radiographic parameters observed during examinations of the injured knee at the time of surgery and at follow-up. PMID- 1424962 TI - Autoplastic grafting from the iliac wing: surgical technique, indications and complications. AB - The authors describe the surgical technique used to obtain (by anterior and posterior access) autoplastic bone from the ilium in 186 oncological cases. Indications, the results obtained and the principal causes of complications are discussed. PMID- 1424963 TI - Pulsing electromagnetic fields (PEMFs) in spinal fusion: preliminary clinical results. AB - Pulsing electromagnetic fields (PEMFs) were used during the postoperative management of 31 patients submitted to lumbosacral posterolateral fusion (PLF). The fusions were stimulated with PEMFs during the first 2 of the 4 months of postoperative immobilization. Consolidation of PLF was obtained in 20 of the 31 patients after 2 months of stimulation, thus, healing time was cut in half. After 4 months, fusion was observed in 30 out of the 31 cases submitted to stimulation (96%). PMID- 1424964 TI - Avulsion of the long head of the triceps in kidney transplant. AB - The authors describe a case of avulsion of the long head of the triceps in a patient with kidney transplant. An analysis of the case and a review of the literature suggest weakening of the osteotendinous junction due to the associated action of renal osteodystrophy and cortisone therapy. PMID- 1424965 TI - One case of fracture of the tibial tuberosity in the adult. AB - The authors report a case of fracture of the anterior tibial tuberosity in an adult. The discussion involves the etiopathogenetic differences of fractures occurring in the adult, as compared to avulsion-fracture in the young patient. The individual features of an unusual direct trauma of the knee could explain the rareness of the clinical case presented. PMID- 1424966 TI - Epiphyseal plate fracture-separation of the olecranon: description of one case. AB - A rare case of traumatic olecranal epiphyseal plate fracture-separation in a patient aged 14 years is described. Non-surgical treatment was not capable of guaranteeing fracture reduction. Thus, internal fixation with tension band wire method, like in fracture of the same type in the adult, was used. PMID- 1424967 TI - [Continuing education in surgery]. PMID- 1424968 TI - [Advance consent and guardianship in consent for medical intervention]. PMID- 1424969 TI - [The geriatric amputee after release from successful rehabilitation]. PMID- 1424970 TI - [Endoscopic approaches to the thorax and abdomen]. PMID- 1424971 TI - [The thoracic-mediastinal approaches]. PMID- 1424972 TI - [Abdominal and retroperitoneal approaches]. PMID- 1424973 TI - [Surgical approaches to important arterial blood vessels]. PMID- 1424974 TI - [Lung embolisms in a surgical patient sample. A retrospective study over 9 years]. AB - In a retrospective study of surgical patients during a period of 9 years 296 cases of pulmonary embolism were recorded by analysing autopsy findings and perfusion pulmonary scans. The frequency of pulmonary embolism among patients who underwent a surgical procedure was 0.55%, the frequency of lethal pulmonary embolism was 0.15%. In autopsy disseminated micro-pulmonary embolism were often found (n = 129, 44%). With regard on the preceding operation a high frequency of pulmonary embolism after septic abdominal surgery (1.5%) and vascular surgery (0.9%) became obvious, especially after operations on the abdominal or thoracic aorta (2.1 resp. 4.8%). In 198 cases venous thrombosis were found. 104 (52%) of these were located in the cranial venous system and in 46 patients there was a connection to the site of central venous lines. PMID- 1424975 TI - [Incidence of carcinoma in follicular neoplasia of the thyroid gland]. AB - Within four years 1376 thyroid operations were performed. In 152 = 11% a follicular or oncocytic tumor was found, 20 = 13% of these were classified as carcinoma. Seven of these were of the grossly invading type, raising suspicion of malignancy already pre- and intraoperatively while 13 encapsulated tumors were found by the pathologist only. If preoperatively a cold nodule or a nodular goitre was described, the carcinoma incidence was about 16%, while warm or hot nodes showed a carcinoma in 2%. Besides tumors of < 1 cm in diameter where we found no carcinoma the size of follicular tumors had no influence on the incidence of carcinomas. PMID- 1424976 TI - [Electromyography findings of pelvic floor muscles in patients with anorectal incontinence]. AB - In the presented study the electromyographical signs of the sphincter muscle of 14 patients with incontinence of the faeces are described and compared with those of a group of continent controls. We found significant differences in the duration of the action potential, the average amplitude, the frequency of polarity turns and the integral of the curves. The application of automatic EMG analysers allows exact differentiation between neurogenic and myogenic disturbances as well as conclusions about the functional integrity of the m. sphincter ani externus and m. puborectalis. The electromyography as a dynamic diagnostic method is a valuable enrichment of the equipment for diagnostic evaluation of the diseases of the pelvic floor. It will be of increasing importance in the differential diagnosis of the incontinence of the faeces and of pudendus nerve lesions as well as in any disease in which a denervation of the parietal or visceral muscles of the pelvic floor is involved. PMID- 1424977 TI - [Necrotizing fasciitis. Case report and review of the literature]. PMID- 1424978 TI - [Necrotizing fasciitis. Case report and review of the literature]. AB - The necrotizing fasciitis is an infection with no or only a small trauma. It is a rapidly progressing process especially with necrosis and edema of subcutaneous fat and adjacent fascia underlined by systemic toxicity but spearing of skin and muscle by the initial process. Late recognition and lack of immediate aggressive surgical treatment contribute to the distressingly high mortality. Early and complete debridement offers the best chance for cure. PMID- 1424979 TI - [Transformation of a fistula into Kaposi's sarcoma of the rectum. A clinical follow-up over 7 years]. PMID- 1424980 TI - [Inversion of Meckel's diverticulum with consecutive small intestine invagination -a rare cause of ileus]. PMID- 1424981 TI - [Streptococcal infection after herniotomy: a rare, life-threatening complication]. PMID- 1424982 TI - Code domains in tandem repetitive DNA sequence structures. AB - Traditionally, many people doing research in molecular biology attribute coding properties to a given DNA sequence if this sequence contains an open reading frame for translation into a sequence of amino acids. This protein coding capability of DNA was detected about 30 years ago. The underlying genetic code is highly conserved and present in every biological species studied so far. Today, it is obvious that DNA has a much larger coding potential for other important tasks. Apart from coding for specific RNA molecules such as rRNA, snRNA and tRNA molecules, specific structural and sequence patterns of the DNA chain itself express distinct codes for the regulation and expression of its genetic activity. A chromatin code has been defined for phasing of the histone-octamer protein complex in the nucleosome. A translation frame code has been shown to exist that determines correct triplet counting at the ribosome during protein synthesis. A loop code seems to organize the single stranded interaction of the nascent RNA chain with proteins during the splicing process, and a splicing code phases successive 5' and 3' splicing sites. Most of these DNA codes are not exclusively based on the primary DNA sequence itself, but also seem to include specific features of the corresponding higher order structures. Based on the view that these various DNA codes are genetically instructive for specific molecular interactions or processes, important in the nucleus during interphase and during cell division, the coding capability of tandem repetitive DNA sequences has recently been reconsidered. PMID- 1424983 TI - Meiotic chromosome condensation and pairing in Saccharomyces cerevisiae studied by chromosome painting. AB - Non-isotopic high resolution in situ hybridization was applied to cytological preparations of sporulating yeast cells. Ribosomal DNA (rDNA) and chromosome V specific recombinant lambda clones were used to tag individual chromosomes and chromosome subregions. This allowed the study of chromosome behaviour during early meiotic prophase. It was found that chromatin becomes condensed and homologous DNA sequences then appear to become aligned prior to synaptonemal complex formation. PMID- 1424984 TI - Gene mapping studies confirm the homology between the platypus X and echidna X1 chromosomes and identify a conserved ancestral monotreme X chromosome. AB - The identification of the sex chromosomes in the three extant species of Prototherian mammals (the monotremes) is complicated by their involvement in a multivalent translocation chain at the first division of male meiosis. The platypus X chromosome, identified by the presence of two copies in females and one in males, has been found to possess a suite of genes that have been mapped to the X chromosomes of all eutherian and metatherian mammals. We have extended gene mapping studies to a member of the only other extant monotreme family, the echidna, which has a G-band equivalent X1 chromosome, as well as a smaller X2. We find that the five human X-linked genes (G6PD, GDX, F9, AR and MCF2) map to the echidna X1 chromosome in locations equivalent to those on the platypus X. These results confirm that the echidna X1 is the original X chromosome in this species, and identify a conserved ancestral monotreme X chromosome. PMID- 1424985 TI - Identification of human satellite DNA sequences associated with chemically resistant nonhistone polypeptide adducts. AB - A fraction of DNA fragments of highly purified and completely unfolded eukaryotic DNA inevitably remains associated with chemically resistant nonhistone DNA polypeptide complexes. This fraction can be isolated by nitrocellulose filtration because the polypeptide-associated DNA fragments are retained on nitrocellulose filters while bulk DNA passes through the filters. The fraction of AluI fragmented DNA from human placenta retained on filters as a result of the binding factors (R-DNA, approximately 12%) represents a subset of genomic sequences with a sequence complexity different from unfractionated DNA and DNA recovered in the filtrate (F-DNA). DNA sequences prevalent in the retained fraction were detected by differential plaque hybridization of a recombinant lambda gt10 library with radiolabeled F- and R-DNA fractions. Several recombinant phages showing much stronger hybridization signals with the R-DNA probe than with the F-DNA probe were selected, plaque-purified and analyzed. Analysis of the inserts of such clones showed that repetitive DNA sequences of the alphoid dimeric and tetrameric family, satellite III and satellite III-like sequences are highly enriched in the retained fraction, which indicates that these sequences specifically attract the polypeptides involved in the tightly bound and resistant complexes. This property of repetitive sequences is of interest since tandemly repetitive sequences have been suggested to code for locus-specific fixation and stabilization of the chromatin fiber in the cell nucleus. PMID- 1424987 TI - MSA-36: a chromosomal and mitotic spindle-associated protein. AB - We have identified a novel M(r) 36,000 protein (MSA-36) that has a complex cell cycle dependent distribution. This protein is first detected in interphase nuclei just prior to the onset of chromosome condensation. MSA-36 is found along condensing chromosomes and is a component of the centromere through metaphase. At anaphase, this protein is no longer detected in association with the chromosomes but appears at the forming stembodies and subsequently within the intercellular bridge at either side of the midbody. At the completion of cell division, the amount of MSA-36 in the bridge appears to decline concurrent with the appearance of this protein briefly within the reforming nucleus. To investigate whether MSA 36 is an active component of the chromosome or a passive passenger protein, we studied the behaviour of this protein in cells exhibiting premature chromosome condensation and in cells during and following recovery from mitotic arrest. These studies suggest that MSA-36 is not essential for a variety of major chromosome-associated events. PMID- 1424986 TI - A cDNA clone for a novel nuclear protein with DNA binding activity. AB - In an effort to identify trans-acting factors regulating specific genes, we cloned a novel human gene, DBP-5. The cDNA clone contains a predicted open reading frame coding for a potential 1,179 amino acid protein. The mRNA corresponding to DBP-5 is ubiquitously distributed, and the gene is phylogenetically conserved. Immunofluorescence analyses with several cell lines indicate that the protein is localized to the nucleus. Sequence analysis revealed unusual features of the predicted protein structure, including four completely conserved repeats. The phylogenetic conservation of DBP-5, the ubiquity of its expression, its nuclear localization, and its ability to bind DNA sequences, raise the possibility that DBP-5 may play a role in the organization of interphase chromatin and/or in transcriptional regulation. PMID- 1424988 TI - Chromosome ends in Chironomus pallidivittatus contain different subfamilies of telomere-associated repeats. AB - Tandemly repeated 340 bp sequences, TA repeats, are present in seven of the eight pairs of chromosome ends in Chironomus pallidivittatus, being absent from the telocentric left end of chromosome four. We have previously shown that the family of TA repeats consists of four main subfamilies. One subfamily is composed of a master unit and the other three contain derived units, each of which has a small region where the master sequence is highly mutated. Here we find that there are considerable variations in numbers of TA repeats between animals and for the same telomere in different animals. We also show that the seven telomere pairs containing TA repeats differ with regard to the content of derived subfamilies. The master unit is probably present in all seven pairs. Two of the derived units are exclusively present in two telomere pairs. The third derived unit shows a more irregular distribution. Some of the telomeres have highly variable contents of such units among animals. Subfamilies thus have different behaviour as reflected in their stable and variable patterns of distribution between individual telomeres. PMID- 1424989 TI - The DNA fragments produced by AluI and BstNI digestion of fixed mouse chromosomes. AB - AluI and BstNI restriction endonucleases were used to study cytological and biochemical effects on centromere DNA in fixed mouse chromosomes. These enzymes were employed, as it is known that AluI is incapable of attacking major satellite DNA, contrary to BstNI that is known to cut this DNA fraction into monomers of 234 bp. After digestion in situ, electrophoretic analysis was carried out to characterize the DNA purified (1) from the material remaining on the chromosomes and (2) from the material solubilized from chromosomes. The DNA was then transferred to a nylon filter and 32P-labelled major satellite DNA was used as a probe for hybridization experiments. Other preparations were simply stained with Giemsa after digestion in situ with AluI and BstNI. Our results show that although restriction endonuclease cleavage primarily depends on DNA base sequence, this factor is not always sufficient to explain nuclease-induced cytological effects. In fact, the structural organization of peculiar regions such as the centromeres of mouse chromosomes might affect cleavage efficiency when restriction enzyme digestion is performed in situ. PMID- 1424990 TI - Chromosoma Prize 1992. PMID- 1424991 TI - Distribution of XhoI and EcoRI family repetitive DNA sequences into separate domains in the chicken W chromosome. AB - Fluorescence in situ hybridization using as probes three biotinylated or digoxigenin-labeled chicken W chromosome-specific repeating DNA units (0.7 and 1.1 kb XhoI family and 1.2 kb EcoRI family units) suggested that a large fraction of one arm of the W chromosome was occupied by the EcoRI family sequences and that pericentromeric regions were widely occupied by the XhoI family sequences. A minor fraction of the EcoRI family was also present in a narrow region in the proximal half of the other arm. There was a region in the distal half of the latter arm where sequences from neither family hybridized. Evolutionary aspects of the presence of different domains occupied by different repetitive families and the significance of the unhybridized distal region are discussed. PMID- 1424993 TI - Involvement of chromatid cohesiveness at the centromere and chromosome arms in meiotic chromosome segregation: a cytological approach. AB - Kinetochores and chromatid cores of meiotic chromosomes of the grasshopper species Arcyptera fusca and Eyprepocnemis plorans were differentially silver stained to analyse the possible involvement of both structures in chromatid cohesiveness and meiotic chromosome segregation. Special attention was paid to the behaviour of these structures in the univalent sex chromosome, and in B univalents with different orientations during the first meiotic division. It was observed that while sister chromatids of univalents are associated at metaphase I, chromatid cores are individualised independently of their orientation. We think that cohesive proteins on the inner surface of sister chromatids, and not the chromatid cores, are involved in the chromatid cohesiveness that maintains associated sister chromatids of bivalents and univalents until anaphase I. At anaphase I sister chromatids of amphitelically oriented B univalents or spontaneous autosomal univalents separate but do not reach the poles because they remain connected at the centromere by a long strand which can be visualized by silver staining, that joins stretched sister kinetochores. This strand is normally observed between sister kinetochores of half-bivalents at metaphase II and early anaphase II. We suggest that certain centromere proteins that form the silver-stainable strand assure chromosome integrity until metaphase II. These cohesive centromere proteins would be released or modified during anaphase II to allow normal chromatid segregation. Failure of this process during the first meiotic division could lead to the lagging of amphitelically oriented univalents. Based on our results we propose a model of meiotic chromosome segregation. During mitosis the cohesive proteins located at the centromere and chromosome arms are released during the same cellular division.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1424992 TI - Deficiency of X and Y chromosomal pairing at meiotic prophase in spermatocytes of sterile interspecific hybrids between laboratory mice (Mus domesticus) and Mus spretus. AB - The normal association between the X and Y chromosomes at metaphase I of meiosis, as seen in air-dried light microscope preparations of mouse spermatocytes, is frequently lacking in the spermatocytes of the sterile interspecific hybrid between the laboratory mouse strains C57BL/6 and Mus spretus. The purpose of this work is to determine whether the separate X and Y chromosomes in the hybrid are asynaptic, caused by failure to pair, or desynaptic, caused by precocious dissociation. Unpaired X-Y chromosomes were observed in air-dried preparations at diakinesis, just prior to metaphase I. Furthermore, immunocytology and electron microscopy studies of surface-spread pachytene spermatocytes indicate that the X and Y chromosomes frequently fail to initiate synapsis as judged by the failure to form a synaptonemal complex between the pairing regions of the X and Y chromosomes. Several additional chromosomal abnormalities were observed in the hybrid. These include fold-backs of the unpaired X or Y cores, associations between the autosome and sex chromosome cores, and autosomal univalents. The occurrence of abnormal autosomal and XY-autosomal associations was also correlated with cell degeneration during meiotic prophase. The primary breakdown in hybrid spermatogenesis occurs at metaphase I (MI), with the appearance of degenerated cells at late MI. In those cells, the X and Y are decondensed rather than condensed as they are in normal mouse MI spermatocytes. These results, in combination with the previous genetic analysis of spermatogenesis in hybrids and backcrosses with fertile female hybrids, suggest that the spermatogenic breakdown in the interspecific hybrid is primarily correlated with the failure of XY pairing at meiotic prophase, asynapsis, followed by the degeneration of spermatocytes at metaphase I. Secondarily, the failure of XY pairing can be accompanied by failure of autosomal pairing, which appears to involve an abnormal sex vesicle and degeneration at pachytene or diplotene. PMID- 1424994 TI - The ultrastructure of the chromosome periphery in human cell lines. An in situ study using cryomethods in electron microscopy. AB - We studied the chromosome periphery in human HeLa and TG cells using cryomethods in electron microscopy. A contrasted layer of peripheral chromosomal material (PCM) was visible in cryo-ultrathin sections of mitotic cells. This PCM was composed of closely packed fibrils associated with granules. The PCM did not cover the entire chromosome surface but was found around most of the chromosomes and even between two chromatids. The organization of the PCM was not affected by colchicine treatment of mitotic cells. In cells prepared by quick-freezing, the PCM appeared to be a fibrous material at the chromosome periphery, and was also associated with granules that resembled inter-chromatin granules in size and shape. At higher magnification, direct contacts between the chromosomes and the fibrils of the PCM were observed. The cryotechniques used are known to preserve the native organization of cells. Therefore, the architecture of the perichromosomal region analysed presumably corresponds to that in vivo during mitosis. These observations show that in HeLa and TG cells, a particular structure present at the chromosome periphery in the form of PCM is persistent and ubiquitous. In addition, we showed by immunolabelling that the PCM is the specific site of accumulation of nucleolar antigens during mitosis. These two results, i.e. the identification of specific morphological structures and the compartmentation of proteins, indicate that this layer is a specific region of mitotic cells. PMID- 1424995 TI - Male and female segregation distortion for heterochromatic supernumerary segments on the S8 chromosome of the grasshopper Chorthippus jacobsi. AB - The mode of inheritance of supernumerary segments located on three different chromosome pairs was investigated in controlled crosses with specimens of the grasshopper Chorthippus jacobsi. While extra segments located on chromosomes M5 and M6 showed Mendelian inheritance, that on S8 did not. Thus, the two supernumerary heterochromatic chromosome segments located distally on the S8 chromosome accumulated through non-Mendelian transmission through both sexes. The observed transmission patterns may be explained by gametic selection for spermatozoa carrying segmented S8 chromosomes, in addition to meiotic drive for segmented S8 chromosomes in heterozygous females. The significance of these findings for the maintenance of these polymorphisms in natural populations is discussed. PMID- 1424996 TI - The Drosophila nuclear protein Bx42, which is found in many puffs on polytene chromosomes, is highly charged. AB - The Drosophila nuclear protein Bx42 is present in a set of transcriptionally active puffs on polytene chromosomes. cDNA clones coding for this protein were isolated from a lambda gt11 expression library. The two Bx42 transcripts are ubiquitously expressed and are already detectable in early stages of development. The corresponding genomic region, in 8C7-8, was isolated and sequenced. Both transcripts direct the production of the same basic, highly charged 547 amino acid protein with a calculated 61.1 kDa molecular weight. PMID- 1424997 TI - [A study of the effect of fish oils on the risk factors of cardiovascular and cerebrovascular diseases]. AB - In this study 22 normotensive (NT) and 12 essential hypertensive (EHT) subjects were included to test the possibility that fish oils might influence the blood pressure, plasma lipids and fibrinogen as well as the erythrocytic membrane lipid composition and pump activity. Each EHT subject was given capsules containing fish oils (6 g/d) for 18 days. At the end of the study, SBP fell (P < 0.05) and plasma fibrinogen level decreased (P < 0.05), while DBP, TG, TC, and HDL-C showed no significant change. The fatty acid composition of erythrocyte phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) showed the following changes: in PE, C22:6, C20:5 increased (P < 0.05; P < 0.01), CI18:1 decreased (P < 0.01); in PC C22:6, C22:4 increased (P < 0.05; P < 0.01). The activity of Na+, Ca2+ max, CaM-stimulated Ca2+ pumps increased (P < 0.05; P < 0.01; P < 0.01). As compared to NT, EHT subjects had higher C20:4 in both PE (P < 0.05) and PC (P < 0.01) and lower C18:2 in PC. It is also shown in this study that EHT subjects have higher C20:4 in both PE (P < 0.05) and PC (P < 0.01) and lower C18:2 in PC as compared to NT ones. PMID- 1424998 TI - [Prognosis and factors predicting the long-term prognosis of myocardial infarction]. AB - 200 cases of consecutively admitted acute myocardial infarction (AMI), who had survived for at least 2 weeks, were studied prospectively. 193 cases were followed-up for 0.5-27 (average 15) months; 41 of them (21.2%) had cardiac events, including 3 sudden cardiac death (1.6%) and 35 obvious cardiac failure (18.1%). 11 patients died of heart failure and 4 of reinfarction. Before discharge, noninvasive tests were done: LVEF < or = 40%, age > or = 60, maximum value of creatinine-phosphokinase > or = 1000 IU/dl and positive ventricular late potential were the 4 factors of high risk. Patients with 3 or 4 positive risk factors had poorer prognosis, if they were compared with those with one or none. PMID- 1424999 TI - [Evaluation of head-chest lead ECG in the diagnosis of acute right ventricular infarction]. AB - The clinical features, hemodynamic parameters, Wilson's lead and head-chest (H-C) lead ECG of 23 cases with acute right ventricular infarction (ARVI) were analyzed. Results showed that 13 cases revealed clinical right heart failure, but 10 of them had clear lung fields. 11 cases showed hypotension. 20 cases had mean right atrial pressure (MRAP) > or = 10 mmHg. The remaining 3 cases had MRAP between 8 mmHg and 10 mmHg, but it was > or = 10 mmHg after volume loading. The ratio of MRAP to pulmonary wedge pressure was > 0.65 and the right ventricular stroke work index < 5.0 g.m/m2 in all the 23 cases. ST elevation > or = 1 mm in V3R to V6R was found in 12 cases (52%), while ST elevation > or = 1 mm in HV3R to HV8R in 20 cases (87%). The results showed that the diagnostic accuracy for ARVI with H-C lead (right chest) ECG is higher than that with Wilson's lead. H-C ECG is better correlated with hemodynamics in patients with ARVI. PMID- 1425000 TI - [A study of measuring cardiac output in patients during mechanical ventilation with CO2 rebreathing method]. AB - Measurement of cardiac output with CO2 rebreathing method and thermodilution method was carried out in seven COPD patients undergoing mechanical ventilation. Mixed venous PCO2 could be measured reasonably well with CO2 rebreathing method. There was a very significant positive correlation between the CO2 method and thermodilution method for measuring cardiac output (r = 0.9130, P < 0.01). The change of cardiac output before and after infusion of sodium nitroprusside could be reflected by CO2 rebreathing method. We conclude that the cardiac output in COPD patients undergoing mechanical ventilation could be measured reasonably well with CO2 rebreathing method. PMID- 1425002 TI - [24-hour esophageal pH monitoring. An analysis of 21 cases]. AB - Esophageal pH monitoring was carried out with self-made portable pH recorder in 21 subjects for 24 hours under normal conditions. The results were as follows: the number of physiological gastroesophageal reflux (GER, pH < 4) was less than 23 times; the percentage of GER duration calculated by dividing the cumulative time of pH less than 4 by the total monitoring time was less than 1.4; the percentage was about 2 in upright position and less than 0.2 in lying position; the duration of the longest reflux episode was less than 5 minutes; the physiological gastroesophageal reflux occurred more often in upright position; while the pathological GER took place both in upright and lying position. Our study also indicated that the degree of esophagitis had no relation with the type of GER. PMID- 1425001 TI - [Renal lesions of post-hepatitis cirrhosis]. AB - There have been many reports on renal lesions of alcoholic cirrhosis, but not on those of post-hepatitis cirrhosis (PHC) up to present. A clinical and pathological observation on PHC was carried out prospectively in 18 and retrospectively in 34 cases. Renal specimens were examined with light and electron microscopy and immunopathological methods (immunofluorescence and peroxidase anti-peroxidase). Clinically, recurrent gross hematuria was observed in 2 and wild urinary abnormality in 17 cases. One case developed renal failure and the remaining 32 cases had no clinical evidence of renal involvement. Light microscopy showed wild mesangial lesions in 44 cases and glomerular basement membrane (GBM) thickening with segmental splitting in 29 and diffuse splitting in 2 cases. Massive protein deposition was found in the GBM, mesangium (Ms) and tubular basement membrane as well as the epithelium and endothelium. Immunopathological examination showed massive deposition of various immunoglobulins and complements in GBM and Ms, with IgG dominant in 8, IgM dominant in 7, IgA dominant in 6 and "full house" in 11 cases. HBsAg was detectable in GBM and Ms in 5 cases (9.6%) and HBcAg in one. Focal interstitial fibrosis and lymphocytic infiltration were found in 15 (28.3%). Our data revealed that renal lesions of post-hepatitis cirrhosis are different from those of the so called "cirrhotic glomerulonephritis" in certain aspects. They are characterized by definite GBM involvement and massive deposition of immunoglobulins and complements. Its pathogenesis may be more complicated than that of other types of liver cirrhosis. PMID- 1425003 TI - [Analysis of 59 cases of non-traumatic sudden death in various neurological diseases]. AB - Sudden death is a common complication of myocardial infarction, necrotic pancreatitis and other diseases. Physicians usually neglect the possibility of neurological disorders. 59 cases of sudden death among 314 autopsied cases with neurological diseases were analyzed. The most frequent cause of neurological sudden death was cerebrovascular disease (CVD). It was present in 53 (89.9%) cases. 48 of them had hemorrhagic CVD. 37 of these 48 cases were due to hypothalamic lesions. In 37 cases general autopsy was performed; pathological abnormalities of heart, lungs, stomach etc, were found in 28 of them. In conclusion, the size and location of the lesion correlated with the prognosis of the disease. Concomitant multiple organ damage may deteriorate the lesion. Awareness of sudden death resulting from CVD may elevate the rate of correct diagnosis. PMID- 1425004 TI - [A comparative trial of levo-praziquantel and praziquantel in the treatment of human Clonorchis sinensis infection]. AB - Seventy patients with clonorchis sinensis infection were divided randomly into two groups and treated with levo-praziquantel and praziquantel in the same dosage of 12.5 mg/kg twice a day for two consecutive days (total dosage of 75 mg/kg). Follow-up stool examination three and six months after treatment showed that the egg negative conversion rates with levo-praziquantel group were 92.86% and 92.59%, while those of praziquantel group were 58.62% and 53.57% respectively. The results showed that levo-praziquantel was significantly superior to praziquantel (P < 0.001). The side reactions in both group were mild and transient. PMID- 1425005 TI - [A laboratory and clinical study of induced differentiation therapy by all trans retinoic acid in acute promyelocytic leukemia]. AB - According to investigations, it was shown that peripheral blood WBC count increased, percentage of promyelocytes increased, differentiation features emerged, protein kinase C (PK-C) activity elevated, intracellular lysozyme content increased, CFU-F productivity increased and typical t (15; 17) disappeared, when induced differentiation therapy with all trans-retinoic acid (RA) was carried out in patients with acute promyelocytic leukemia. Comparison between RA group and RA+Harringtonin/Ara-C group showed no significant difference in most of the parameters; the curative effect was same in both groups. Complete remission (CR) rate was achieved in 92.6% (25/27 cases) of the patients in the entire group. In order to increase CR rate, prevention and treatment for haemorrhagic complications are critical. Patients with hyperleukocytosis (WBC > or = 100 x 10(9)/L) should be treated with intensive combined therapy as well as aggressive prevention of haemorrhage and pathological changes of lung and brain. PMID- 1425006 TI - [Rethrombosis after coronary thrombolysis]. PMID- 1425007 TI - Polyfunctional cytokines: IL-6 and LIF. Introduction. PMID- 1425008 TI - The action of interleukin 6 and leukaemia inhibitory factor on liver cells. AB - The hepatic action of cytokines has generally been analysed in terms of the acute phase response of the liver. The qualitative and quantitative changes in the expression of plasma proteins serve as defining criteria for cytokine function. Interleukin 6 (IL-6) and leukaemia inhibitory factor (LIF) are representatives of a group of cytokines which display strikingly similar effects in both human and rodent liver cells. Hallmarks of the action of these cytokines are the stimulation of type 2 acute-phase plasma proteins and enhancement of the effect of interleukin 1 (IL-1) or tumour necrosis factor alpha (TNF-alpha) on type 1 acute-phase plasma proteins. The transcriptional activation of the various acute phase plasma protein genes involves common cis-acting regulatory elements whose sequences and location relative to the transcription start site vary from gene to gene. The activity of the IL-6- and LIF-responsive genes depends in part on transcription factors including several members of the C/EBP family, JunB and the glucocorticoid receptor. The expression of these transcription factors is in turn under cytokine-specific control. In a few cases, expression is temporally correlated with the activation of 'late' acute-phase protein genes. The finding that structurally distinct cytokines interact with separate receptors but elicit an almost identical liver cell response demands a reassessment of the contribution of each factor to the in vivo acute-phase response. PMID- 1425009 TI - Further studies of the distribution of CDF/LIF mRNA. AB - Differentiation choices in the haemopoietic and nervous systems are controlled in part by instructive factors. The cholinergic differentiation factor (CDF, also known as leukaemia inhibitory factor, LIF) affects the development of cultured cells from both systems. To understand the role of CDF/LIF during normal development in vivo, we have begun to localize its mRNA in the late fetal and postnatal rat. Application of reverse transcriptase-polymerase chain reaction and RNase protection methods reveals that CDF/LIF mRNA levels are developmentally modulated in both haemopoietic and neural tissues. A target tissue of cholinergic sympathetic neurons, the footpads that contain the sweat glands, express high levels of this mRNA (relative to mRNA for actin and beta 2-microglobulin). Levels in targets of noradrenergic neurons are lower, but do undergo significant changes during development. Signals are also detected in selective regions of the adult brain, and in embryonic skeletal muscle. This finding in muscle may be significant for motor neurons, because CDF/LIF is a trophic factor for these neurons in culture. Embryonic liver, neonatal thymus and postnatal spleen express CDF/LIF mRNA, and expression in gut is the highest of all tissues examined. The selective tissue distribution and developmental modulation of CDF/LIF mRNA expression support a role for this factor in the normal development of several organ systems. PMID- 1425010 TI - Leukaemia inhibitory factor and bone cell function. AB - A bone-resorbing product of mouse spleen cells found to have differentiation inducing activity was most probably leukaemia inhibitory factor (LIF). This revealed that LIF is a cytokine active on bone, in addition to its several other sites of action. In organ culture of newborn mouse bone, recombinant LIF promoted bone resorption by a prostaglandin-dependent process. Resorption by isolated rat osteoclasts was also promoted by LIF through an initial action on osteoblasts which was receptor-mediated. Incorporation of [3H]thymidine into DNA was increased by LIF in cells (most probably osteoblasts) of the newborn mouse bones. Osteoblasts have been shown to produce LIF, and the amount is increased by treatment with retinoic acid or TNF-alpha. LIF also acts directly on osteoblasts to inhibit plasminogen activator activity, by stimulating the synthesis of plasminogen activator inhibitor 1 mRNA and protein. The latter actions are very similar to those of TGF-beta. Again like TGF-beta, LIF was ineffective in promoting bone resorption in vitro in fetal rat long bones. These results, together with the in vivo data showing that high circulating levels of LIF in the mouse are accompanied by a substantial increase in trabecular bone mass, indicate that LIF is another cytokine with potent actions on bone and potentially important interactions with other osteotrophic factors. PMID- 1425011 TI - The role of interleukin 6 in megakaryocyte formation, megakaryocyte development and platelet production. AB - Megakaryocytopoiesis is the cellular amplification and differentiation of precursors into immature megakaryocytes, and the cytoplasmic maturation of these megakaryocytes, a process terminating in the release of platelets into the circulation. Interleukin 6 (IL-6) stimulates megakaryocytopoiesis in the bone marrow, increasing platelet numbers in the circulation. IL-6 alone is poorly active on the growth of stem cell populations, but acts in synergy with stem cell factor (c-kit ligand) to expand the committed myeloid progenitor compartments but not the megakaryocyte progenitors. IL-6 has a direct action on megakaryocyte progenitors but only in synergy with low doses of interleukin 3 (IL-3), increasing the number of immature megakaryocytes and enhancing the processes of development into mature megakaryocytes. IL-6 is about 10 times more active on megakaryocytes than on megakaryocyte progenitors in cell culture. It is active alone and will stimulate increases in cell size and DNA content. IL-6 does not appear to stimulate the process of platelet release. IL-6 is found in bone marrow, in both macrophage subsets and megakaryocytes, indicating that it may be an important physiological regulator of both paracrinal (microenvironmental) and autocrinal mechanisms controlling megakaryocyte development in bone marrow. PMID- 1425012 TI - Actions of leukaemia inhibitory factor on megakaryocyte and platelet formation. AB - Leukaemia inhibitory factor (LIF) is able to potentiate megakaryocyte colony formation in cultures of mouse bone marrow cells in the presence of multi-CSF (interleukin 3). Membrane receptors for LIF are present on mouse megakaryocytes and receptor numbers increase with increasing maturation of the cells. When injected into normal mice at doses of 0.2-2 micrograms two to three times daily, LIF induced a rise in platelet numbers, which reached up to twice normal values during the second week of injections. This rise was preceded by a rise first in megakaryocyte progenitor numbers, then in mature megakaryocytes in the bone marrow and spleen. Injections of LIF also marginally accelerated platelet regeneration in mice pre-injected with 5-fluorouracil or subjected to whole-body irradiation and transplantation of marrow cells. In view of similar responses to LIF in parallel studies in primates, clinical trial of LIF in patients with thrombocytopenia is warranted. PMID- 1425013 TI - The role of interleukin 6 in plasmacytomagenesis. AB - Interleukin 6 (IL-6) is a polyfunctional cytokine which regulates the immune response, the acute-phase reaction and haemopoiesis. IL-6 plays a critical role in differentiation of B cells into plasma cells, and is a potent growth factor for plasmacytomas and myelomas. A relationship between IL-6 and polyclonal plasma cell abnormalities has been demonstrated. Abnormal production of IL-6 was first suggested to be related to hypergammaglobulinaemia with autoantibody production in patients with cardiac myxoma. A role of IL-6 in the generation of plasmacytoma has also been indicated. In support of these clinical and experimental observations, we demonstrated that transgenic C57BL/6 mice carrying the human IL 6 gene showed a massive polyclonal plasmacytosis with production of autoantibodies. However, the tumour was not transplantable to syngeneic animals. Susceptibility to pristane-induced plasmacytomagenesis is genetically determined- pristane can induce plasmacytomas in BALB/c but not in C57BL/6 mice. IL-6 transgenic C57BL/6 mice were backcrossed to BALB/c mice to elucidate the genetic influence on plasmacytomagenesis. Transplantable monoclonal plasmacytoma with a t(12;15) chromosomal translocation was generated in some of the backcrossed mice, indicating that IL-6 plays a key role in the multistep oncogenesis of plasma cell neoplasia. PMID- 1425014 TI - Interleukin 6 determination in the detection of microbial invasion of the amniotic cavity. AB - A growing body of evidence suggests a role for cytokines in the mechanisms responsible for preterm parturition associated with intrauterine infection. Interleukin 6, a polyfunctional cytokine that is secreted by tissues in the feto maternal interface in response to microbial products, has been implicated in the host response to intrauterine infection. The purpose of this study was to establish whether measurement of amniotic fluid concentrations of interleukin 6 could be of value in the diagnosis of microbial invasion of the amniotic cavity. Fluid was obtained by transabdominal amniocentesis from patients with preterm labour and intact chorioamniotic membranes and cultured for aerobic and anaerobic bacteria and mycoplasmas. Interleukin 6 concentrations were determined by an ELISA validated for human amniotic fluid. An interleukin 6 concentration above 11.2 ng/ml had a 93.7% sensitivity and a 92.3% specificity in the diagnosis of intra-amniotic infection. Moreover, patients with an amniotic fluid interleukin 6 level above 11.2 ng/ml and a negative amniotic fluid culture failed to respond to tocolysis, delivered a preterm infant and showed histological evidence of chorioamnionitis, and their neonates were at risk for congenital infections. PMID- 1425015 TI - Distribution and binding properties of receptors for leukaemia inhibitory factor. AB - The pleiotropic biological actions of leukaemia inhibitory factor (LIF) on haemopoietic cells (macrophages and megakaryocytes), hepatocytes, osteoblasts, pre-adipocytes, embryonic stem cells, myoblasts and neuronal cells must be mediated through the interactions of LIF with specific cellular receptors. The demonstration by equilibrium binding analysis and autoradiography of LIF receptors on all of the above cells and cell lines suggests that each of these pleiotropic effects of LIF is mediated by direct interactions with the responding cells rather than by the indirect release of secondary cytokines. Despite the differing biological effects of LIF on these cells, equilibrium binding, kinetic analyses and receptor internalization studies have all suggested that these cells display essentially identical high affinity LIF receptors. Nevertheless, there is evidence on some cell types (granulocyte-macrophage colony-stimulating factor [GM CSF] transgenic peritoneal cells and F9 embryonal carcinoma cells) for a second class of low affinity LIF receptors (Kd = 1.5 nM versus Kd = 30 pM for high affinity receptors) which, LIF receptors (Kd = 1.5 nM versus Kd = 30 pM for high affinity receptors) which differ from the high affinity receptors only in kinetic dissociation rate. Moreover, the evidence suggests that low and high affinity receptors are structurally related and interconvertible, because detergent solubilization of LIF receptors from any cell type results in the quantitative conversion of high affinity receptors into low affinity receptors. As is the case for other related cytokine receptors, these data suggest that high affinity LIF receptors may be composed of two protein subunits--one responsible for LIF specific low affinity binding and the other responsible for affinity conversion and cell signalling by the receptor. Such a model provides a possible explanation for the pleiotropy of LIF's biological actions. PMID- 1425016 TI - Molecular biology of the leukaemia inhibitory factor gene. AB - Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine that has been identified and characterized in several laboratories by virtue of a number of different biological activities. LIF is encoded by a unique gene located at 11A1 in the mouse and at 22q12 in man. However, loci related to sequences in the 3' untranslated region of the mRNA have been detected and located elsewhere in the genome. The LIF gene from four mammalian species has been cloned and sequenced; the sequences are highly conserved within the coding regions and largely non conserved within the non-coding regions. However, a number of non-coding segments displaying high interspecies similarity are evident; these are candidate control regions. Intriguingly, an exon corresponding to the 5' end of a variant LIF transcript in the mouse that encodes a potentially matrix-associated form of LIF is not conserved in the human, ovine and porcine genes. The promoter region of the LIF gene contains four well-conserved TATA elements, and two start sites of transcription have been identified. Three regions within the 5' flanking region have been identified as important for the function of the LIF promoter, including a candidate repressor sequence. The LIF gene is transcribed at only very low levels in normal tissues, but its expression can be increased by various stimuli. PMID- 1425017 TI - Reconstitution of high affinity leukaemia inhibitory factor (LIF) receptors in haemopoietic cells transfected with the cloned human LIF receptor. AB - cDNA clones encoding the human leukaemia inhibitory factor (hLIF) receptor were isolated by screening a placental cDNA expression library in COS-7 cells with 125I-hLIF. The cloned LIF receptor is a member of the haemopoietin receptor family and comprises a signal sequence (44 amino acids), an extracellular region of two haemopoietin receptor domains and three fibronectin type III domains (789 amino acids), a transmembrane domain (26 amino acids) and a cytoplasmic domain (238 amino acids). The LIF receptor is expressed in COS-7 cells as a 190 kDa glycoprotein that specifically binds human LIF with low affinity, but does not bind mouse LIF. Clones encoding a soluble form of the homologous mouse LIF receptor have been isolated, suggesting complex interactions between the various forms of LIF ligand and receptor in vivo. The LIF receptor is most related to the gp130 signal-transducing component of the IL-6 receptor, a feature that may provide a molecular basis for the intertwined biologies of LIF and IL-6 in the absence of obvious structural similarly between the ligands. Mouse B9 plasmacytoma cells transfected with the human LIF receptor display novel high affinity LIF receptors that are presumed to consist of transfected receptors in association with endogenous mouse high affinity-converting subunits. Unlike the low affinity human LIF receptor, the mixed species high affinity receptor is capable of binding mouse LIF. PMID- 1425019 TI - The action of interleukin 6 on lymphoid populations. AB - We have analysed the role of IL-6 in activation of human lymphocytes isolated from peripheral blood. We found little effect of IL-6 on proliferation of T cells. IL-6 did stimulate production of IgM by B cells. However, it did not behave as a terminal differentiation factor and was required only during the first two days of the culture. Under most conventional stimulation conditions T cells themselves produce little or no IL-6. High IL-6 production could be induced by stimulating the cells with a combination of phorbol-12-myristate 13-acetate (PMA) and anti-CD28 antibodies. PMID- 1425018 TI - The molecular biology of interleukin 6 and its receptor. AB - Functional pleiotropy and redundancy are characteristic features of cytokines. Interleukin 6 (IL-6) is a typical example: IL-6 induces cellular differentiation or expression of tissue-specific genes; it is involved in processes such as antibody production in B cells, acute-phase protein synthesis in hepatocytes, megakaryocyte maturation, cytotoxic T cell differentiation, and neural differentiation of PC12 (pheochromocytoma) cells. It promotes growth of myeloma/plasmacytoma cells, T cells, keratinocytes and renal mesangial cells, and it inhibits growth of myeloid leukaemic cell lines and certain carcinoma cell lines. The IL-6 receptor consists of two polypeptide chains, a ligand-binding chain (IL-6R) and a non-ligand-binding, signal-transducing chain (gp130). Interaction of IL-6 with IL-6R triggers the association of gp130 and IL-6R, and the signal can be transduced through gp130. Association of gp130 with IL-6R is involved in the formation of high affinity binding sites. This two-chain model has been shown to be applicable to receptor systems for several other cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, IL-5 and nerve growth factor (NGF). The pleiotropy and redundancy of cytokines may be explained on the basis of this unique receptor system. PMID- 1425020 TI - Regulation of leukaemic cells by interleukin 6 and leukaemia inhibitory factor. AB - Interleukin 6 (IL-6) and leukaemia inhibitory factor (LIF) can have pleiotropic effects on different cell types. M1 myeloid leukaemic cells respond to IL-6 with activation of a terminal differentiation programme which includes activation of genes for certain haemopoietic regulatory proteins (IL-6, IL-1 alpha, IL-1 beta, granulocyte-macrophage colony-stimulating factor [GM-CSF], M-CSF, tumour necrosis factor and transforming growth factor [TGF] beta 1) and for receptors for some of these proteins, thus establishing a network of positive and negative regulatory cytokines. IL-6 and some other cytokines also induce during differentiation sustained levels of transcription factors that can regulate and maintain gene expression in the differentiation programme. M1 leukaemic cells induced to differentiate with IL-6 undergo programmed cell death (apoptosis) on withdrawal of IL-6, and can be rescued from apoptosis by IL-6, IL-3, M-CSF, G-CSF or IL-1, but not by GM-CSF. These differentiating leukaemic cells can also be rescued from apoptosis by the tumour promoter TPA (12-O-tetradecanoylphorbol-13-acetate) but not by the non-tumour-promoting isomer 4-alpha-TPA, and rescue from apoptosis can be achieved by different pathways. Apoptosis can also be induced in undifferentiated M1 leukaemic cells by expression of the wild-type form of the tumour suppressor p53 protein and IL-6 can rescue the cells from this wild-type p53-mediated apoptosis. There are clones of M1 cells that differentiate with IL-6 but not with LIF and another M1 clone that differentiates with either IL-6 or LIF. Differentiation induced by IL-6 or LIF is inhibited by TGF-beta 1. The pleiotropic effects of LIF, like those of IL-6, are presumably also in a network of interacting regulatory proteins. PMID- 1425021 TI - Regulation of gene expression in the hypothalamus: hybridization histochemical studies. AB - Hybridization histochemistry has bridged molecular biology and neuroanatomy to provide nearly dynamic views of gene expression in the brain--perhaps especially in the hypothalamus. These snapshots of transcript levels with precise anatomical localization have revealed new insights into gene regulation in the hypothalamus under specific conditions. Magnocellular neurons in the paraventricular and supraoptic nuclei produce vasopressin and oxytocin. Transcript levels for these hormones are affected by hyperosmolality, as are those for many other neuropeptides. Patterns of gene expression in the magnocellular neurons in these nuclei during development and under different physiological conditions have been studied less extensively. The parvocellular neurons of the paraventricular nucleus produce corticotropin-releasing factor and thyrotropin-releasing hormone. Expression of the corticotropin-releasing factor gene is regulated by glucocorticoids. Physiological stresses, which activate the hypothalamo-pituitary adrenal axis, also affect gene expression in the parvocellular paraventricular nucleus. Thyrotropin-releasing hormone is synthesized in a different set of parvocellular neurons in the paraventricular nucleus and in other neurons of the hypothalamus. Expression of the thyrotropin-releasing hormone gene is regulated by thyroid hormone. The suprachiasmatic nucleus contains neurons that produce vasopressin or vasoactive intestinal polypeptide in a circadian rhythm. Future studies using combinations of classical neuroanatomical techniques, hybridization histochemistry and immunohistochemistry will further our understanding of hypothalamic responses to various stimuli. PMID- 1425022 TI - Feedback regulation of thyrotropin-releasing hormone gene expression by thyroid hormone in the hypothalamic paraventricular nucleus. AB - Hypothyroidism caused by chemical or surgical thyroidectomy or hypophysectomy causes a substantial increase in the content of thyrotropin-releasing hormone (TRH) mRNA and proTRH exclusively in cells of the medial and periventricular paravocellular subdivisions of the hypothalamic paraventricular nucleus (PVN). This response may be important to raise the anterior pituitary thyrostat to promote increased secretion of thyroid-stimulating hormone (TSH) and to induce the secretion of a more biologically active TSH. The increase in TRH mRNA can be obliterated by stereotaxic implants of hormonally active L-triiodothyronine (T3) placed into the anterior hypothalamus but not by implants of the hormonally inactive 3,5'-diiodo-L-thyronine (T2); we therefore suggested that T3 has a direct action on TRH-containing cells of the PVN. Ablation of brainstem catecholaminergic projection fields to the PVN (known to stimulate TRH secretion) has no effect on TRH mRNA expression; beta 1 thyroid hormone receptor mRNA is present in extracts of the PVN. Euthyroid levels of serum T3 in hypothyroid animals achieved via intraperitoneally implanted osmotic minipumps are not associated with a return of PVN levels of TRH mRNA to normal unless circulating T3 levels are raised into the hyperthyroid range (1.7 times normal). This requirement is similar to that needed to normalize nuclear thyroid hormone receptor levels in the anterior pituitary of hypothyroid animals, suggesting that in addition to circulating T3 monodeiodination of T4 to T3 within the brain must also contribute to feedback inhibition of TRH mRNA. As Type II deiodinase activity is absent or very low in the PVN and does not rise with hypothyroidism, we propose that an alternative source for T4 monodeiodination exists within the central nervous system. PMID- 1425023 TI - Co-localization of neuroactive substances in the endocrine hypothalamus. AB - In addition to their characterizing secretory products, both magnocellular and parvocellular neurosecretory neurons are now known to express other neuroactive substances. Parvocellular neurons that make corticotropin-releasing factor (CRF) for example are capable of synthesizing at least seven neuropeptides. Some of these, like arginine vasopressin (AVP), interact with CRF at the level of the anterior pituitary to promote corticotropin secretion, and, like CRF, are regulated negatively by glucocorticoids and positively by at least some stressors. others are inert in these two contexts but are responsive to various challenges. Magnocellular neurosecretory oxytocin- and AVP-containing neurons are capable of producing similarly broad and distinctive complements of neuroactive principles. These are typically expressed at levels far lower than those of the nonapeptides, suggesting local modulatory effects on oxytocin and/or AVP secretion at the level of the posterior lobe. Differential regulation of coexisting molecules within magnocellular neurons by systemic challenges and steroid hormones has also been described. Secretory products of magnocellular neurons may gain access to the anterior pituitary via exocytotic release at the level of the median eminence or through vascular links between the posterior and anterior lobes, suggesting another form of 'co-localization' by which the two neurosecretory cell types may interact in the control of stress and perhaps other pituitary-mediated responses. PMID- 1425024 TI - Gene memory in neuroendocrine and behavioural systems. AB - Several examples of sex steroid hormone actions on rat brain and behaviour show that initial hormone exposures may be followed by enduring neuronal alterations, apparent long after the hormone itself has disappeared. Precedents from non neuronal systems led to the concept of 'gene memory'. We are studying genomic structural alterations in rat hypothalamic neurons to account for these effects. The preproenkephalin gene is turned on by oestradiol in rat brain neurons in a tissue-specific and genetic sex-specific manner. Levels of preproenkephalin mRNA in the ventromedial hypothalamus correlate tightly with oestradiol-dependent reproductive behaviour. Our results indicate a tissue-specific pattern of DNA methylation in the enkephalin promoter. Putative binding sites for several transcription factors have been described in the preproenkephalin gene promoter; a role for some of these factors in regulating expression of the gene has been demonstrated. PMID- 1425025 TI - Neuronal-glial and synaptic remodelling in the adult hypothalamus in response to physiological stimuli. AB - Activation of certain neurosecretory systems of the mammalian hypothalamus induces remodelling of the conformation of their neurons and glial cells. During stimulation of the hypothalamo-neurohypophysial system, astrocytic coverage of oxytocinergic somata and dendrites diminishes and their surfaces become extensively juxtaposed. In the neurohypophysis and median eminence, stimulation evokes a retraction of glial processes and an increase in the contact area between neurosecretory terminals and the perivascular space. These changes are reversible and glial coverage returns to normal upon cessation of stimulation. Neuronal-astrocytic rearrangements also occur in the arcuate nucleus in response to changes in sex steroid levels. The significance of such modifications is a matter of speculation. In the hypothalamic nuclei they may permit synaptic remodelling that takes place concurrently; in the neurohaemal structures they may facilitate neuropeptide release. We know little about the cellular mechanisms involved but glia and neurons of these systems express certain molecules implicated in cell-cell interactions in the developing central nervous system, such as the polysialylated isoform of the neural cell adhesion molecule; this may allow them to manifest their capacity for morphological plasticity in adulthood. The factors inducing the changes vary in the different structures: while oxytocin, in synergy with steroids, appears essential to the induction of the changes in the oxytocinergic system, oestrogen alone is critical in the arcuate nucleus; in the neurohypophysis noradrenaline appears important. PMID- 1425026 TI - Neural control of the synthesis and release of luteinizing hormone-releasing hormone. AB - Preovulatory surges of luteinizing hormone (LH) depend upon neurotransmitter activation of neurons that secrete LH-releasing hormone (LHRH, gonadotropin releasing hormone GnRH) and noradrenaline plays a pivotal role in this critical event. The interaction is amongst noradrenaline and other neurotransmitters such as GABA (gamma-aminobutyric acid), opiates, serotonin and excitatory amino acids (N-methyl-D-aspartate, NMDA) on LHRH neuronal activity are complex. GABA and opiates suppress the presynaptic release of noradrenaline but only GABA also directly affects the responsiveness of LHRH neurons to noradrenaline. Morphine induces the release of serotonin which either directly or indirectly via other neurotransmitters (e.g. dopamine) sensitizes LHRH neurons to the stimulatory effects of noradrenaline. NMDA rapidly induces LH release but whether this drug directly affects the activity of LHRH neurons is not known. The neuronal release of LHRH is modulated by the action of oestrogen on these various neurotransmitter systems. Antioestrogens, when placed into the medial preoptic area of otherwise completely oestrogenized rats, block LH surges; LHRH mRNA levels in such animals resemble those in 9-day castrated rats. Normally, LHRH message levels increase about the time of increased noradrenaline secretion just before the LH surge. NMDA rapidly releases LH and LHRH mRNA levels are significantly raised within 15 minutes and remain so over the next 45 minutes. Thus, it seems that stimuli which evoke LHRH release also increase LHRH mRNA transcription to replenish the hormone released during the LH surge. PMID- 1425027 TI - The neurobiology of primate puberty. AB - In higher primates the protracted prepubertal phase of development is occasioned by a mechanism that suppresses pulsatile hypothalamic gonadotropin-releasing hormone (GnRH) secretion from late infancy until the onset of puberty and thereby guarantees, in the juvenile, the quiescence of the pituitary-gonadal axis. Studies from our laboratory have employed the rhesus monkey, a representative higher primate, as an experimental paradigm. GnRH release has been measured using luteinizing hormone secretion by the in situ pituitary as a bioassay for the hypothalamic hormone. The nature of the prepubertal brake on pulsatile GnRH release in the monkey has been probed using physiological, neuroanatomical and neuropharmacological approaches. Such studies have led to the view that the prepubertal hiatus in pulsatile GnRH release results from a withdrawal in late infancy of a synchronized frequency-facilitated afferent neural input to the GnRH network, which in all other respects appears to exhibit properties identical to those in the postpubertal animal. The mechanism timing the onset of puberty, i.e. that responsible for the reactivation of synchronous activity in the GnRH network, is posited to be under the control of a central neural time- or growth tracking device. PMID- 1425028 TI - Hypothalamic transplantation. AB - Tissue transplantation aided in formulating the neurohumoral hypothesis of anterior pituitary function. The concept of a hypophysiotropic region within the hypothalamus stemmed from experiments in which pituitary tissue was transplanted into the brain. Restoration of aberrant function of the central nervous system by transplants has been reported in two neuroendocrine models: the antidiuretic hormone-deficient Brattleboro rat and the gonadotropin-releasing hormone deficient hypogonadal mouse. Neural transplants into the Brattleboro rat result in the survival of axons containing antidiuretic hormone but reversal of the physiological defect has not been confirmed. In the hypogonadal mouse grafts of preoptic area tissue into the third ventricle have restored pituitary hormone synthesis and secretion and gonadal activity, leading to nearly normal reproductive function. The gonadotropin-releasing hormone axons specifically innervate the median eminence of the hypothalamus, their normal target, which raises interesting questions of neurobiological graft/host interactions. The hpg model has been used to investigate factors affecting graft survival; by suitable immunosuppression it has been possible to reverse the hypogonadism with grafts of rat preoptic area tissue. Perhaps the most dramatic recent development has been the restoration of circadian rhythmicity to suprachiasmatic nucleus-lesioned hamsters by grafts of similar tissue. The rhythmicity restored is typical of the donor tissue. PMID- 1425029 TI - Regulation of prolactin transformation in the rat pituitary. AB - We have investigated the mechanisms involved in the inhibition by dopamine of the transformation of prolactin within the anterior pituitary of the lactating rat. The degree of inhibition depends on the intracellular age of prolactin, being greater in newly synthesized (<1 hour) and in older (>12 hours since biosynthesis) hormone and lesser in prolactin synthesized 4-8 hours earlier. Transformation occurs in prolactin granules and involves an increase in oligomeric forms of prolactin at the expense of the monomeric form. A reversible disulphide-linked mechanism may be involved in dopamine inhibition of prolactin transformation; it is dependent upon the intracellular and/or intragranular pH via a Na+/H+ exchange mechanism. Transient suppression of dopamine inhibition may lower the intracellular/intragranular pH and subsequently cause transformation of the hormone. Developmentally, dopamine secretion by tuberoinfundibular neurons is seriously impaired and the response of pituitary lactotrophs to dopamine is reduced in adult rats deprived of milk prolactin during Days 2-5 post partum. These results suggest milk prolactin ingested during a critical post partum period may exert an organizational effect upon dopamine secretion and its function on the pituitary lactotroph during adulthood. PMID- 1425030 TI - What can we learn from sampling hypophysial portal blood? AB - Since it has become possible to sample hypophysial portal blood from sheep without totally compromising pituitary function, several important features of the secretion of hypothalamic hormones have been elucidated. The secretion of gonadotropin-releasing hormone (GnRH) has been detailed most thoroughly with the important observation that each pulsatile discharge of luteinizing hormone (LH) is the direct result of a large secretory episode of GnRH from the hypothalamus. There is high fidelity in the GnRH relationship in terms of frequency and amplitude. During the LH surge, additional factors such as an alteration in the degree of enzymic degradation of GnRH may be important physiological mechanisms. The secretion of factors that control the release of growth hormone (GH), prolactin and adrenocorticotropic hormone (ACTH) have also been studied. Hypothalamic factors controlling GH and ACTH release do not bear such an explicit relationship to the secretory episodes of pituitary hormone as seen with the GnRH/LH axis. The factor involved in the acute stress-induced release of prolactin has not yet been identified in sheep. PMID- 1425032 TI - [An epidemiological survey of blindness and low vision in Hebei Province]. AB - Following the national unified criteria and methods, an epidemiological survey of blindness and low vision was carried out in Hebei Province from April to June, 1987. In 77,948 persons examined, there were 291 cases of bilateral blindness, representing a prevalence of 0.37% (male 0.29%, female 0.45%, urban areas 0.19%, plain areas 0.42%, and mountainous areas 0.36%). The prevalences of monocular blindness, bilateral and monocular low vision were 0.72%, 0.57% and 0.30% respectively. Subjects over 60 years of age had significantly higher prevalences of bilateral blindness and low vision. The chief blinding diseases were cataract, trachoma complications, corneal disease and glaucoma, in order of importance. PMID- 1425031 TI - [A morphological study of retinal damages by intraocular lead]. AB - The morphological changes in the retina were observed by light and electron microscopy at intervals after implantation of lead into the vitreous of rabbit eyes. The results revealed progressive structural disorders under both modalities of examination, indicating that lead had toxic effects on the retina. PMID- 1425033 TI - [A microdialmeter for measurement of the anterior chamber depth]. AB - A microdialmeter is designed to measure the anterior chamber depth by determining the distance advanced by the slitlamp that is focused first on the posterior surface of the cornea and then on the anterior surface of the lens. An isosceles right triangular block is fixed onto the slitlamp to transform its anterior posterior movement into the transverse direction to be measured conveniently by the microdial with a precision of 0.01 mm. PMID- 1425034 TI - [Genetic segregation analysis of retinitis pigmentosa]. AB - Comprehensive genetic segregation analysis performed in 150 pedigree of retinitis pigmentosa (RP) showed that the disease manifested genetic heterogeneity. Families of the mating type Affected x Normal were autosomal dominant (AD), with 80% of penetrance and no sporadic cases. Families of the mating type Normal x Normal were 80% autosomal recessive (AR), with 20% of sporadic cases. In the present series, the RP pedigrees were AD in 13.3%, X-linked in 2.7%, AR in 67.3% and sporadic in 16.7%, and most sporadic cases were nongenetic. It was also demonstrated that, with the conventional mode of pedigree analysis, the proportions of AR and AD cases were underestimated, and the proportion of sporadic RP was overestimated. PMID- 1425035 TI - [Genetic predisposition to retinoblastoma(Rb)]. PMID- 1425036 TI - [Parafoveal retinal telangiectasis and changes of the capillary free zone in non diabetic patients]. AB - Microaneurysms, hard exudates, hemorrhages and/or edema in the macular region were observed in 10 eyes of 10 non-diabetic patients. By fluorescein angiography, parafoveal retinal telangiectasis was found in all cases. Deformation, enlargement and boundary disruption of the foveolar avascular zone were discernible in most cases, as were unevenness of capillary spacing, small areas of non-perfusion and leakage of dye in some cases. Analysis and calculations of the foveolar avascular zone were done with the Model-970 Quantmet computerized image analysis system. The data showed that the values of circumference, vertical diameter and roundness of the avascular zone differed significantly from those of the 10 normal control eyes. PMID- 1425037 TI - [Exudative retinal detachment in the pregnancy-induced hypertension syndrome]. AB - 22 cases of pregnancy-induced hypertension syndrome with exudative retinal detachment were studied. Fluorescein angiography performed in 5 patients 7-14 days post-parturition revealed choroidal circulatory disturbances and retinal pigment epithelial damages, while the retinal capillaries also showed damages of varying degrees. The authors regarded the former as the primary pathological basis for the retinal detachment, with the latter also playing a pathogenic role. The incidence and the source of fluid of the retinal detachment in relation to general edema, proteinuria, and hypertension were discussed. PMID- 1425038 TI - [Vitrectomy plus air tamponade for treatment of retinal detachment with proliferative vitreoretinopathy]. AB - Closed vitrectomy, membrane peeling, intraocular air tamponade and scleral encircling were performed for 35 consecutive cases of retinal detachment with proliferative vitreoretinopathy (PVR), comprising 2 cases of grade C2, 4 cases of grade C3, 6 cases of grade D1, 17 cases of grade D2, and 6 cases of grade D3. 21 eyes (60%) attained anatomic retinal reattachment with improved visual acuity in 20 eyes. The authors believed that vitrectomy combined with membrane peeling was a logical approach to the treatment of retinal detachment with PVR. The surgical success was related to the extent of membrane peeling, and intraocular air tamponade was a simple and effective adjunctive measure. PMID- 1425039 TI - [Vitrectomy of vitreal cryoextraction for treatment of intravitreal cysticercosis]. AB - Thirteen (13) patients of intravitreal cysticercosis were treated by vitrectomy (10 patients) or vitreal cryoextraction (3 patients) with successful removal of the parasites. The surgical procedure was described with discussions. Vitrectomy was especially advantageous to late cases of the disease. PMID- 1425040 TI - [Clinical analysis of radiation optic neuropathy]. AB - As a result of enhanced cure rate and survival time of patients with nasopharyngeal carcinoma (NPC) treated by radiotherapy, sequelae of radiation injury to the optic nerve are becoming important, of which the authors report 5 cases (6 eyes) observed in the past 2 years. The diagnoses were based on rapid visual deterioration or blindness in one or both eyes, with visual field defects, signs of papillary ischemic optic atrophy under fluorescein angiography, normal ERG but reduced amplitude and prolonged latency or even extinction of VEP, onset of the malady within 7 years after the initial session of radiotherapy, and survival of the patient over 1 year with no signs of NPC recurrence or metastasis. Good vision was saved in 2 eyes treated with hyperbaric oxygen. PMID- 1425041 TI - [An image analysis system for optic disc in glaucoma]. AB - An image analysis system for glaucomatous optic disc was developed. The key for optic disc measurement was to trace accurately the boundaries of the optic cup and disc. The 2-dimension measurement modality adopted was the heuristic boundary tracing method, and the 3-dimension measurement was performed by observation of the photographs, arbitrary selection of points, and automatic plotting and calculation. In order to measure accurately the optic disc in glaucoma follow-up, the authors made use of the cross correlation line by line scanning method, after proper correction of the photographs, to detect any positional shift in two photographs. By clinical verification, the 95% confidence criterion of normal optic cup boundary shifting was 1.7 pixels. The optic disc diameter of the disc images was over 200 pixels, and any shift over 2 pixels (1%) would have clinical significance, which was a high degree of precision. PMID- 1425042 TI - [Analysis of penetrating corneal regrafting in 29 cases]. AB - Repeated penetrating keratoplasty was retrospectively analyzed in 29 cases followed up 1-4 years postoperatively. The regraft remained clear in 10 eyes (34.5%). The major causes of regrafting failure were similar to those of the initial keratoplasty, i.e. immunologic rejection, postoperative angle-closure glaucoma, and donor graft failure. PMID- 1425043 TI - [The effect of horizontal strabismus surgery on the refractive status in children]. AB - The refractive changes in 84 children (155 eyes) following horizontal strabismus surgery and in 97 children (181 eyes) without surgical intervention were studied. The results indicated that the spherical refraction and axis of astigmatism were not significantly affected by the operation, especially when both recession and resection were done on the same eye; however, the cylindrical refraction changed markedly within 6 weeks of surgery. These changes would be minimized and become stable 6 weeks after the operation, suggesting that the proper time for a cycloplegic refraction was 6 weeks after a horizontal strabismus surgery. PMID- 1425044 TI - [The purification of bovine IRBP and its uveitogenic action]. AB - The interphotoreceptor retinoid-binding protein, IRBP, shuttles the retinoid between photoreceptor cells and the pigment epithelium. It also induces experimental autoimmune uveoretinitis (EAU). The authors first purified IRBP in China by Con A Sepharose affinity chromatography in conjunction with the purification of bovine retinal S-antigen by ion-exchange chromatography. EAU was successfully induced by injection of emulsified IRBP 50 micrograms with Freund's complete adjuvant into the footpad of Lewis rats. It was characterized by panophthalmia with severe damage to the posterior retina, and lymphocytes predominated the inflammatory infiltration that included mononuclear and polymorphonuclear cells. PMID- 1425045 TI - Balloon expulsion test facilitates diagnosis of pelvic floor outlet obstruction due to nonrelaxing puborectalis muscle. AB - We compared balloon expulsion, defecography, colonic transit times, anal manometry, and electromyography in 21 patients with severe constipation. Defecography demonstrated nonrelaxation of the sphincter during straining in all patients. Only 12 patients were unable to expel a balloon. Colonic transit was normal (five) or showed rectosigmoid delay (seven). All 12 patients were offered biofeedback. The nine patients able to expel a balloon had normal colonic transit (six) or colonic inertia (two). Rectosigmoid delay was due to severe intussusception in one patient. Anal manometry and pudendal nerve latencies revealed no difference between those who could and those who could not expel a balloon. Balloon expulsion seems to be a more reliable way to diagnose pelvic floor outlet obstruction due to nonrelaxation of the puborectalis muscle. Nonrelaxation of the sphincter on defecography should be correlated with balloon expulsion and colonic transit studies. PMID- 1425046 TI - Internal rectal intussusception: results of surgical repair. AB - Twenty-four patients with obstructed defecation due to rectal intussusception diagnosed by defecography were treated with rectopexy either by the Wells technique (9 patients) or by Orr's operation (15 patients). After follow-up from one to eight years, defecography demonstrated disappearance of the intussusception in 22 patients. None of the patients were completely relieved of their symptoms. Nine (41 percent; 95 percent confidence limits: 21-64) were improved and 13 were unchanged (59 percent; 95 percent confidence limits: 36-79), with no difference between the two procedures. One patient with solitary rectal ulcer was improved, and the ulcer disappeared. Four patients with moderate preoperative incontinence became continent postoperatively, but obstructed defecation was only improved in two of these patients. It is concluded that rectal intussusception is probably a secondary phenomenon in patients with obstructed defecation and that a conservative attitude toward surgery should be adopted. PMID- 1425047 TI - Combined anorectal manometry and defecography in 50 consecutive adults with fecal incontinence. AB - Fifty consecutive patients presenting with fecal incontinence were evaluated prospectively with anorectal manometry, defecography, and other tests of anorectal function to assess the clinical utility of defecography in fecal incontinence. Leakage of contrast at rest and failure to narrow the anorectal angle with pelvic squeezing were specific but not sensitive predictors of decreased sphincter pressures as determined by manometry. Thus, after manometry, defecography provided no additional information regarding sphincter strength. Retention of contrast in large rectoceles or incomplete rectal evacuation at defecography had excellent correlation with the presence of clinical symptoms of outlet obstruction constipation (present concurrently with incontinence) and indicated an etiology of outlet obstruction symptoms. Defecography may provide useful information in incontinent patients with outlet obstruction constipation symptoms but has little additive value to anorectal manometry in incontinent patients without such symptoms. PMID- 1425048 TI - Prognostic significance of location of lymph node metastases in colorectal cancer. AB - The prognostic value of stage of lymph node metastases was evaluated in 357 patients who underwent curative resection for colorectal cancer. Subdivision of Dukes C patients according to the number of positive nodes revealed that the five year disease-free survival rate (5DFS) was 63 percent in the patients with one to three nodes and 53 percent in those with four or more nodes (not significantly different). Classification according to the location revealed that 5DFS was 70 percent in those who had only local node metastases (n1+), compared with 40 percent in those who had distant node metastases along the major vessels (n2+) (P < 0.001). Twelve of 38 n2+ patients had only one distant node metastasis with no local node involvement (skip metastasis). They had lower 5DFS than the n1+ patients who had three or more positive local nodes (35 percent vs. 57 percent). We conclude that the location, rather than the number, of nodal metastases has a higher impact on prognosis in colorectal cancer patients. PMID- 1425049 TI - Retained mucosa after double-stapled ileal reservoir and ileoanal anastomosis. AB - A study was undertaken to assess the incidence of inflammation and dysplasia in retained mucosa after double-stapled ileoanal reservoir (IAR) for mucosal ulcerative colitis (MUC). Between September 1988 and February 1992, 56 patients with MUC underwent an IAR. Forty-five patients had a double-stapled IAR (DS-IAR), seven patients had a transanal pursestring stapled IAR (PS-IAR), and four patients had a PS-IAR with mucosectomy. Distal donuts obtained from the stapled IAR were submitted for pathologic review in 55 patients. Nine patients had only small bowel, connective tissue, and/or muscle noted on review. Mucosa was qualified as squamous epithelium (SE), transitional epithelium (TE), or columnar epithelium (CE). All samples were examined for evidence of inflammation and dysplasia. Four patients had SE only, one patient had TE, and 18 had CE. In addition, three patients had SE and CE, seven patients had SE and TE, two patients had CE and TE, and nine patients had all three types. The distance from the dentate line to the anastomosis ranged from 0 to 2.5 cm (mean, 1 cm). In 19 patients (35 percent), the distal donut revealed MUC. Of these 19 patients, six had persistent MUC (43 percent) at the time of subsequent biopsy. An additional four patients had MUC evident on follow-up biopsy but not on distal donuts; two of these four patients had no mucosa in their distal donuts. Only one of the patients with evidence of MUC on donuts and/or biopsy experienced any symptoms referable to active MUC (1.8 percent). None of the specimens examined had any evidence of dysplasia. In 31 patients, no MUC was present in the initial donuts or follow-up biopsies. Although the double-stapled technique appears safe, periodic monitoring is suggested. PMID- 1425050 TI - Postoperative adjuvant radiotherapy in Astler-Coller stages B2 and C rectal cancer. AB - Between 1979 and 1983, 127 patients with Stages B2 or C rectal cancer treated with surgery plus postoperative adjuvant radiotherapy (RT group) and 122 patients treated with surgery alone (S group) were compared to evaluate the effect of postoperative radiotherapy on survival and disease recurrence. Each group was stratified into subgroups according to stage and tumor differentiation as follows: Subgroups BW (Stage B2 and well-differentiated tumor), BM (Stage B2 and moderately differentiated tumor), CW (Stage C and well-differentiated tumor), CM (Stage C and moderately differentiated tumor), and P (poorly differentiated tumor). Ninety-five percent of the patients were followed until death or, if alive, to five years after surgery. Postoperative radiotherapy was associated with a reduced five-year survival rate in Subgroup BW (67 vs. 87 percent; P = 0.02). In the remaining subgroups of the RT group, there was a statistically insignificant trend toward a worse survival rate (56 vs. 65 percent, 47 vs. 64 percent, 41 vs. 46 percent, and 50 vs. 36 percent for Subgroups BM, CW, CM, and P, respectively). The local failure rates for the S group and RT group were 10 vs. 23 percent (P = 0.15) in Subgroup BW, 32 vs. 21 percent (P = 0.4) in Subgroup BM, 24 vs. 25 percent (P = 0.6) in Subgroup CW, and 18 vs. 18 percent (P = 0.6) in Subgroup CM, respectively. Eight percent (9/127) had severe or life threatening radiation-related complications. Postoperative adjuvant radiotherapy alone did not improve the survival of patients with Stages B2 or C rectal cancers. It may have led to worsened survival in the subgroup of patients with well-differentiated Stage B2 rectal cancer. PMID- 1425051 TI - Outcome of ileorectal anastomosis for Crohn's colitis. AB - One hundred thirty-one patients underwent ileorectal anastomosis (IRA) for Crohn's colitis. Preoperatively, 84 patients (63 percent) were found to have mild or moderate proctitis and 47 (37 percent) had rectal sparing. Sixty-eight (52 percent) had associated small bowel disease, and 20 (15 percent) had perianal disease. Sixty-five IRAs were performed at the time of subtotal colectomy, while 56 were done after previous surgery. Anastomotic leaks occurred in four patients. There were no operative deaths. Thirteen patients (10 percent) with protecting stomas never underwent closure. Among the remaining 118 patients with functioning IRAs, 30 (23 percent) required later proctectomy and 16 (13 percent) required proximal diversion, with the mean period with a functioning IRA in these 46 patients being 4.1 years (range, 6.2 months-12.7 years). An additional 13 patients required preanastomotic resection and neo-IRA, and 11 required proximal small bowel resection. The mean duration of function of all 118 IRAs was 9.2 years. At the time of review, after a mean follow-up of 9.5 years, 72 patients (61 percent) retained a functioning IRA, with 44 being free of disease, while 28 were being treated with steroids or antidiarrheal medication. The mean stool frequency was 4.7 per day. In patients with Crohn's colitis, IRA should be considered as an alternative to proctocolectomy if the rectum is not severely diseased and sphincter function is not compromised. PMID- 1425052 TI - Incidence, outcome, and proposed management of isolated abscesses complicating acute left-sided colonic diverticulitis. A prospective study of 140 patients. AB - In a prospective evaluation of 140 consecutive patients with acute left-sided colonic diverticulitis demonstrated by computerized tomography (CT) in all cases, 22 (16 percent) were found to have an associated abscess without peritonitis. Thirteen of these 22 required surgery (seven during the first stay and six from 2 to 11 months after the acute episode; median, three months). Nine patients were treated conservatively, eight of whom are now totally asymptomatic 24 months after the initial attack (range, 10-47 months). There were 10 mesocolic abscesses (seven treated with antibiotics alone), nine pelvic abscesses (seven requiring surgery), and three intra-abdominal abscesses, all operated upon. These results suggest that mesocolic abscesses can usually be managed conservatively without drainage; should surgery be necessary, en bloc resection with immediate anastomosis can usually be safely performed. Pelvic and intraabdominal abscesses behave more aggressively and usually require a two-stage surgical procedure when initial percutaneous drainage cannot be performed or is felt to be hazardous. PMID- 1425053 TI - Sonography in acute colonic diverticulitis. A prospective study. AB - The clinical value of high-resolution real-time sonography for the diagnosis of acute and complicated colonic diverticulitis was prospectively studied in 130 consecutive patients with abdominal complaints, because of which the disease entered into differential consideration. The results of ultrasound investigation were compared with those of clinical examination on admission. Regarding history and initial clinical evaluation, diverticulitis was graded as "highly suspected" in 19 (36.5 percent) out of a total of 52 patients with later proven colonic diverticulitis (prevalence 40 percent), as "possible but equivocal" in 24 (46.2 percent), and as "very unlikely" in the remaining nine (17.3 percent) patients. Ultrasonography enabled the diagnosis of diverticulitis with an overall accuracy of 97.7 percent, a sensitivity of 98.1 percent, and a specificity of 97.5 percent. The predictive values of positive and negative ultrasound examinations were 96.2 percent and 98.5 percent, respectively. The echomorphologic features of acute diverticulitis include visualization of a colon segment presenting with local tenderness on gradual compression, which showed hypoechogenic thickening of the wall and a targetlike appearance in transverse view due to inflammatory changes and muscular thickening. Sonographic signs of peridiverticulitis (hyperechoic halo) were found in 96 percent of patients, echogenic diverticula in 86 percent. Twelve (92 percent) of 13 abdominal abscesses were detected on initial ultrasound examination and could be treated by percutaneous drainage in seven cases, while six required surgical intervention. These results indicate that high-resolution sonography with graded compression is highly sensitive and specific for the imaging diagnoses of acute colonic diverticulitis and complicating abscess. PMID- 1425054 TI - Clinical trial of oral diosmin (Daflon) in the treatment of hemorrhoids. AB - A double-blind, comparative, controlled study on the effectiveness of the addition of oral diosmin (Daflon; Lab. Servier, Orleans, France) and placebo to a conservative regimen of bulk laxative in the treatment of acute symptoms of first degree and second-degree internal hemorrhoids was undertaken in 100 patients. The diosmin and placebo groups, with 50 patients each, were comparable in age, sex, symptoms, and the severity of the underlying hemorrhoids. During the first four days, the patients received 12 tablets in three divided doses, and then they received two tablets twice daily for another 10 days. Subjective and objective changes were assessed at the 4th and 14th days of treatment. The diosmin group showed statistically significant objective improvement (P < 0.01) without accompanying subjective improvement on the fourth day. However, at day 14, there was no significant difference in either subjective or objective improvement between the two groups. Two cases in the placebo group were taken out of the trial on the fourth day owing to clinical deterioration. No side effect of diosmin was detected in this study. PMID- 1425056 TI - Open sesame: tips for traversing the anal canal. AB - The key points for a minimally traumatic and pain-free anal intubation are an informed patient, gentle technique, plenty of lubricant, a relaxed, supportive atmosphere, and gradual inward pressure on the instrument or finger. Also important are knowledge of the direction of the anal canal, sideways introduction of the flexible endoscope, and the technique of gaining anal relaxation by asking the patient to push down. PMID- 1425055 TI - Extensive varices of ileocecum. Report of a case. AB - A man was admitted to our hospital because of intestinal reddish bleeding. Colonic varices were found at the cecum by colonoscopy. Angiography of the superior mesenteric artery showed that blood vessels were scant from the end of the ileum to the ascending colon. An operative view revealed the varices, but there was no trace of the ileocecal vein. This case, presenting a deficit of the ileocecal vein, indicated that the blood flow could not return via the ileocecal vein, and therefore there was an outflow through the varices to the surrounding intestine or abdominal veins. Such a case is probably unrepresented in the literature because it was caused by the total deficiency of the ileocecal vein and it was in the right colon. PMID- 1425058 TI - Rectal procidentia--an unresolved surgical problem. PMID- 1425057 TI - The present role of colostomy in the management of trauma. AB - The role of colostomy in the treatment of abdominal trauma has changed over the past several decades. Primarily as a result of its successful use in military settings, colostomy initially was the mainstay of treatment for penetrating injury to the colon, rectal injury, and some forms of blunt trauma. Subsequent civilian experience with the techniques of primary repair of penetrating colon injury resulted in a decrease in the number of colostomies performed. Coupled with this experience, early data on adverse outcome from colostomy closure tended to support the trend of the ever-diminishing place of colostomy for trauma. Colostomy has always been used for two purposes in trauma care: prevention or arrest of fecal contamination of the peritoneal cavity and diversion of the fecal stream. Despite the decreased need for colostomy in some forms of penetrating colon injury, there are several conditions that still utilize colostomy to accomplish one or both of these purposes. Indications for colostomy can now be regarded as absolute or relative depending upon the need for diversion or the requirement to prevent contamination. There are relatively few contraindications to colostomy use. Present results of colostomy closure do not represent excessive risk to the patient and should not impact negatively on the decision to perform a colostomy for trauma. PMID- 1425060 TI - Hemorrhoidectomy with self-retaining retraction. PMID- 1425059 TI - Colorectal anastomosis in second stage Hartmann's procedure using the CEEA Stapler--no enterotomy, no pursestring. PMID- 1425061 TI - Irrigation of the rectal stump decreases the chance of exfoliated cells on staplers. PMID- 1425062 TI - Effects of antiviral agents on chronic hepatitis B. Analysis using Cox proportional hazard model. AB - Two hundred fifteen courses of antiviral treatment including interferon with or without steroid withdrawal, adenine arabinoside with steroid withdrawal, and steroid withdrawal alone were given to 175 patients with HBe-antigen positive chronic hepatitis B. The effectiveness was judged on loss of HBe antigen and formation of anti-HBe, and was compared with 80 controls. According to cumulative HBe seronegative and seroconversion rates as analyzed by the Kaplan-Meier method, interferon with steroid withdrawal increased both the cumulative HBe seronegative and seroconversion rates significantly (P < 0.0001). Adenine arabinoside with steroid withdrawal and interferon alone increased the cumulative HBe seronegative rate only (P < 0.001). The Cox proportional hazard regression model was fitted to the data of 188 cases whose pretreatment liver biopsy specimens were obtained. Among treatment protocols, interferon with steroid withdrawal shortened both the HBeAg-positive period and the duration until anti-HBe becomes reactive significantly (P < 0.0001). Interferon without steroid withdrawal and adenine arabinoside with steroid withdrawal shortened the HBeAg positive interval only (P < 0.05). Among patients' characteristics, female and advanced liver histology were favorable factors. Effects of treatment protocols were analyzed after averaging each parameter of the patients' characteristics. Interferon and adenine arabinoside with steroid withdrawal shortened the HBeAg-positive interval significantly (P < 0.0001 and P < 0.05, respectively), and interferon alone showed a tendency to shorten the interval. In particular, interferon with steroid withdrawal increased the chance of losing HBeAg 7.3 times more than control. The effectiveness of antiviral treatment on chronic hepatitis B, especially the priority of interferon with steroid withdrawal, was thought to be established through this study. PMID- 1425064 TI - Effects of gastric inhibitory polypeptide and glucagon on portal venous and hepatic arterial flow in conscious dogs. AB - Gastric inhibitory polypeptide (GIP) has considerable structural homology with glucagon, which is known to increase liver blood flow. We compared the effects of GIP on portal venous and hepatic arterial flow with those of glucagon in conscious dogs. Injection of GIP significantly increased portal venous flow in a dose-related manner (by 7%, 15%, and 46% at doses of 1, 100, and 500 pmol/kg, respectively). The increase in portal venous flow induced by GIP and glucagon was comparable; however, the increase in portal venous flow after GIP injection reached its peak significantly earlier than that after glucagon injection. Hepatic arterial flow decreased after GIP injection (by 17%, 21%, and 35% at doses of 1, 100, and 500 pmol/kg, respectively), whereas it was not altered by glucagon. Thus, GIP causes significant changes in both portal venous and hepatic arterial flow in conscious dogs. Although structurally related, GIP and glucagon may influence liver blood flow through different mechanisms. PMID- 1425063 TI - Evaluation of [14C]aminopyrine breath test, peripheral clearance of [99mTc]EHIDA, and serum bile acid levels in liver function and disease. AB - The purpose of this study is to evaluate the diagnostic value of the following tests in the assessment of patients with chronic liver disease (CLD) and cholestatic syndrome (CS): (1) aminopyrine breath test, measuring 14CO2 excretion in the expired air, (2) peripheral clearance of [99mTc]EHIDA, and (3) postprandial levels of glycocholic acid (GCA) and glycochenodeoxycholic acid (GCDCA). The results indicate that: (1) 14CO2 2-hr excretion rate is a specific and sensitive marker of liver function, with good correlation with postprandial bile acid levels, [99mTc]EHIDA retention, and the conventional tests of serum albumin and prothrombin time. (2) Peripheral clearance and retention of [99mTc]EHIDA increased in both groups of CLD and CS vs controls, but it does not discriminate between the two. (3) Postprandial bile acids were elevated in CLD, particularly those of GCDCA, whereas GCA levels were significantly elevated in CS compared with CLD. This may be due to increased synthesis and entry into the blood. (4) The combination of [14C]aminopyrine breath test and postprandial levels of GCDCA enhance the diagnostic value, specificity, and sensitivity in the assessment of patients with CLD. PMID- 1425065 TI - Effect of erythromycin on gallbladder emptying in diabetic patients with and without autonomic neuropathy and high levels of motilin. AB - A reduction of gallbladder emptying in response to neural or hormonal stimulation has been reported in patients with diabetes mellitus. Decreased gallbladder emptying may be a key factor in the pathogenesis of gallbladder stones. Few drugs, if any, are able to stimulate gallbladder emptying. However, in a previous study we demonstrated that erythromycin, a macrolide antibiotic, stimulates gallbladder emptying and motilin release in healthy human subjects by an atropine sensitive pathway. Therefore, the present study was designed to evaluate the effect of erythromycin on gallbladder emptying and motilin release in diabetic patients with or without cardiac autonomic neuropathy (AN). Thirteen diabetic patients, six with AN, and 10 healthy subjects were enrolled in the study protocol. Gallbladder emptying was determined by sonography after ingestion of a standard meal and during infusion of erythromycin alone or together with 6 micrograms/kg/hr atropine. We found that 100 mg/hr erythromycin caused a significant reduction in gallbladder volume in both healthy subjects and diabetic patients. The ejection fraction (mean +/- SE) of 45.3 +/- 8.2% and 37.3 +/- 5.0% was similar. The presence of AN had no influence on gallbladder emptying induced by erythromycin. Basal motilin plasma levels were 111.5 +/- 14.5 pmol/liter in diabetic patients and 63.3 +/- 6.0 pmol/liter in healthy subjects (P < 0.01). However, patients with AN had higher (130.0 +/- 11.9 pmol/liter) motilin plasma levels than patients without (74.0 +/- 9.4 pmol/liter, P < 0.01). Erythromycin administration caused an approximately twofold increase in plasma motilin concentrations in healthy subject and patients without AN, but did not stimulate motilin release in neuropathic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425066 TI - Postprandial gallbladder motility and plasma cholecystokinin at regular time intervals after injection of octreotide in acromegalics on long-term treatment. AB - The increased risk of gallstone formation in acromegalics treated with the somatostatin analog octreotide has been related to an impaired gallbladder emptying. To determine the duration of these inhibitory effects, meal-stimulated gallbladder motility, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured in five acromegalics treated for 6-32 months with 200-300 micrograms octreotide daily. Meal tests were performed 45 min, 8 hr and two weeks after the last 100-micrograms subcutaneous dose. Results were compared with those in normal subjects. Integrated postprandial gallbladder contraction (-125 +/- 194 cm3/120 min) and integrated PP secretion (-0.1 +/- 0.2 nmol/liter/120 min) were completely suppressed in the 45-min study, but significantly improved (P < 0.05) when measured 8 hr (1376 +/- 322 cm3/120 min and 3.0 +/- 1.0 nmol/liter/120 min) and two weeks (1437 +/- 263 cm3/120 min and 10.6 +/- 1.6 nmol/liter/120 min) after the last dose of octreotide. The integrated gallbladder contraction in acromegalics at 8 hr was comparable to that at two weeks and to that in normal subjects, but the integrated PP response at 8 hr was significantly smaller (P < 0.05 vs two weeks and vs normals). Integrated plasma CCK secretion at 45 min (0.13 +/- 0.06 nmol/liter/120 min) was not statistically significantly different from the response at 8 hr (0.15 +/- 0.02 nmol/liter/120 min) and from that in normal subjects, but it was significantly increased at two weeks after cessation of octreotide (P < 0.05 vs 45 min and 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425067 TI - Penetration of ceftriaxone and cefoperazone into bile and gallbladder tissue in patients with acute cholecystitis. AB - The penetration of ceftriaxone and cefoperazone into bile and gallbladder tissue was prospectively studied in 21 adult patients undergoing early surgery for acute cholecystitis. Comparable tissue, bile, and serum concentrations of the drugs were demonstrable; however, significantly fewer preoperative doses of ceftriaxone were required for adequate perioperative treatment. In view of its higher serum half-life and superior antibacterial activity toward common biliary pathogens, ceftriaxone appears to be a useful drug for the perioperative management of acute cholecystitis. PMID- 1425068 TI - Gastric surgery and bezoars. AB - We present a series of 56 patients with gastrointestinal bezoar following previous gastric surgery for gastroduodenal peptic ulcer. The following parameters were studied: factors predisposing to bezoar formation (type of previous surgery, alimentation, and mastication), form of clinical presentation, diagnostic tests, and treatment. A bilateral truncal vagotomy plus pyloroplasty had been performed previously on 84% of patients, 44% revealed excessive intake of vegetable fiber, and 30% presented with bad dentition. The most frequent clinical presentation was intestinal obstruction (80%). This was diagnosed mainly by clinical data and simple abdominal radiology. The main exploratory technique for diagnosing cases of gastric bezoar was endoscopy. Surgery is necessary for treating the intestinal forms, and one should always attempt to fragment the bezoar and milk it to the cecum, reserving enterotomy and extraction for cases where this is not possible. The small intestine and stomach should always be explored for retained bezoars. Gastric bezoars should always receive conservative treatment, endoscopic extraction, and/or enzymatic dissolution; gastrotomy and extraction should be performed when this fails. PMID- 1425070 TI - Mucosal damage during intestinal anaphylaxis in the rat. Effect of betamethasone and disodium cromoglycate. AB - In this study, two antiallergic compounds, betamethasone and disodium cromoglycate were tested in an animal model of intestinal anaphylaxis. Rats, immunized with Nippostrongylus brasiliensis, were challenged intravenously with whole worm antigen or saline. Antigen challenge resulted in significant abnormalities: epithelial damage with shorter villi, decreased activity of digestive enzymes, decreased levels of mucosal histamine, a mast cell mediator, and increased blood uptake of [51Cr]EDTA from the lumen. Low-dose betamethasone, 24 and 48 hr before antigen, was not effective in preventing the effects: villus damage and increased [51Cr]EDTA uptake were seen, although mucosal mast cell numbers were significantly reduced by the drug. High-dose betamethasone completely prevented intestinal anaphylaxis: villus height, digestive function, and [51Cr]EDTA recovery in antigen-challenged animals were not significantly different from controls. Mucosal histamine levels and mast cells were significantly reduced in the high dose betamethasone group. Oral disodium cromoglycate did not prevent the abnormalities but provided a slight beneficial effect. PMID- 1425069 TI - Effect of Aeromonas hydrophila enterotoxins on function of mouse phagocytes. AB - Two enterotoxins produced by Aeromonas hydrophila isolate SSU have been characterized in this laboratory. One is a cholera toxin cross-reactive cytolytic enterotoxin (CTC toxin) and the other is a non-cholera toxin cross-reactive cytotonic enterotoxin (non-CTC toxin). The two enterotoxins are capable of causing fluid accumulation in animal models; however, only the CTC toxin is lethal to mice and expresses hemolytic as well as cytotoxic activities. In this study, we have investigated the effects of these two toxins on mouse phagocytes. Four hours after intraperitoneal injection of a sublethal dose (460 micrograms/kg of body weight) of CTC toxin, the chemiluminescence (CL) response of phagocytes in mouse blood was depressed significantly when compared with that observed for controls (intraperitoneal injection of only Hanks' balance salt solution, non-CTC toxin or before treatment with CTC toxin). When fresh whole blood was incubated with various concentrations (2.3, 11.5, 23, 230, 2300 ng/ml) of CTC toxin for 1.5 hr at 37 degrees C, the CL response of blood phagocytes was reduced strikingly in a dose-dependent fashion; however, non-CTC toxin did not inhibit the CL response. The inhibitory effect induced by CTC toxin of the phagocytic function not only was abolished completely, but phagocytosis was enhanced in the presence of interferon-gamma (IFN-gamma). In addition, IFN-gamma alone induced the largest enhancement of the CL response in mouse phagocytes. These results demonstrated that CTC toxin inhibits the phagocytic ability of phagocytes either in vivo or in vitro and that IFN-gamma pretreatment can overcome this toxic effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425071 TI - Prostaglandin- and theophylline-induced C1 secretion in rat distal colon is inhibited by microtubule inhibitors. AB - The aim of the present study was to examine the possible role of microtubules in chloride secretion by distal rat colon stimulated by prostaglandin (PGE2) and theophylline. Distal colonic tissue from male rats was mounted in Ussing chambers, and short-circuit current (Isc) was measured to assess chloride secretion. Three microtubule inhibitors, colchicine, nocodazole, and taxol, all inhibited the stimulated Isc and reduced the 60-min integrated secretory response to PGE2 and theophylline (integral of Iscdt) by 39-52%, whereas the inactive colchicine analog lumicolchicine did not. Atropine and tetrodotoxin had no effect on stimulated chloride secretion. To confirm the source of Isc, unidirectional 22Na+ and 36Cl- fluxes were measured in tissues exposed to lumicolchicine (control) or colchicine. Control tissues absorbed both chloride [5.0 (1.1-8.6) (median and 95% confidence interval) mueq/cm2/hr] and sodium [2.8 (0.9-7.2) mueq/cm2/hr], and this net absorption was reduced by 96% and 79%, respectively, by treatment with PGE2 and theophylline due to an increase in serosal-to-mucosal chloride and sodium movement. Colchicine-treated tissues exhibited similar net basal chloride and sodium absorption that was reduced by 71% and 75%, respectively, by treatment with PGE2 and theophylline. Thus the PGE2- and theophylline-induced increase in chloride secretion was significantly reduced by colchicine (P < 0.05 by Wilcoxon rank-sum test), whereas colchicine had no effect on PGE2- and theophylline-induced changes in sodium fluxes. Furthermore, the colchicine-related changes in stimulated chloride secretion were numerically similar to colchicine-related changes in stimulated Isc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425072 TI - Rectal mucosal ornithine decarboxylase activity is not a useful marker of risk for colorectal neoplasia. AB - Rectal mucosal ornithine decarboxylase activity has been reported to distinguish patients with adenomas from normal controls. In order to further explore this association, we assayed biopsy samples from 119 unselected individuals undergoing routine colonoscopic examinations. The overall mean ODC activity was 127.4 (+/- 93.1 SD) pmol/mg protein/hr. There were no differences by age, sex, or race. Tissue handling and storage influenced ODC activity. Specimens collected and transported on Dry Ice had higher ODC activity than specimens initially frozen in a -20 degrees C freezer. After adjusting for storage and collection method, the activity was similar in subjects with adenomas (126.3 pmol/mg/hr) compared to those without adenomas (128.8 pmol/mg/hr). We conclude that variations in assay technique make comparisons between laboratories difficult. Patients with large bowel adenomas do not necessarily have higher ODC activity in uninvolved rectal mucosa. Further study of the environmental and genetic factors that influence rectal mucosal proliferation may improve our understanding of carcinogenesis in the large bowel. PMID- 1425073 TI - Phenotypic characterization of isolated intraepithelial lymphocytes in patients with ulcerative colitis and normal controls. AB - A method was developed to isolate colonic intraepithelial lymphocytes in patients with ulcerative colitis (N = 8) and normal controls (N = 13) in order to characterize their phenotype using a panel of monoclonal antibodies and flow cytometry. In both groups, the majority of the cells are of the CD3+CD8+ phenotype associated with cytotoxic/suppressor function. The CD4/CD8 ratios were similar. Virtually no B cells or macrophages were found. An increase in cells coexpressing the CD3 and HLA-DR molecules and a decrease in natural killer cells (CD3, CD16+CD56+) were found in ulcerative colitis, but this was not significant. There were no differences in the proportions of CD8+ and CD4+ cells expressing the Leu8 antigen between ulcerative colitis and controls. Thus a population of colonic intraepithelial lymphocytes has been isolated and, although they may be functionally different in ulcerative colitis compared with controls, this cannot be explained in terms of phenotypic characteristics. PMID- 1425074 TI - Changes of colonic vasoactive intestinal peptide and cholinergic activity in rats with chemical colitis. AB - The vasoactive intestinal peptide concentration was examined in the colonic wall and portal venous plasma of rats with chemical colitis by radioimmunoassay, and the colonic localization was determined with immunocytochemistry. Colonic acetylcholine esterase activity was also measured, and the response of vasoactive intestinal peptide to acetylcholine administration was determined. Colitis was induced by administration of dextran sulfate for three months. The chemical colitis was histologically similar to active human ulcerative colitis. We observed a significant increase of immunostained neurons and nerve fibers and a significant rise in the colonic wall vasoactive intestinal peptide content in chemical colitis rats, while plasma concentrations of the peptide did not change significantly. Colonic acetylcholine esterase activity was significantly elevated in colitis rats compared with control rats. Systemic administration of acetylcholine significantly increased the colonic and plasma vasoactive intestinal peptide concentrations in colitis rats. These findings demonstrated a positive association between colitis activity and an increase of vasoactive intestinal peptide and suggested that increased vagal tone promoted the peptide's release. PMID- 1425075 TI - Motility of rabbit proximal colon. Relevance of cholinergic pathways and role of different muscarinic receptor subtypes. AB - To better define the physiologic relevance of the cholinergic muscarinic input to the rabbit colon and the role of different muscarinic receptor subtypes, we studied the effects of atropine, telenzepine (MI antagonist) and DF594 (M3 antagonist) on colonic motility in eight conscious rabbits fitted with bipolar electrodes and strain gauges along the proximal colon. In some experiments, the chronotropic and mydriatic effect of the pharmacological agents were also assessed. Two main patterns of spike activity were identified: short spike bursts (SSBs), which were usually stationary, and long spike bursts (LSBs), which were usually propagated. Both myoelectrical patterns were dose-dependently inhibited by atropine (0.06-4 mumol/kg). Atropine, at the doses of 2-4 mumol/kg, abolished both myoelectrical and mechanical activity. Telenzepine (0.008-0.125 mumol/kg) dose-dependently inhibited migrating LSBs without significant effect on SSBs. Higher doses (0.25-0.5 mumol/kg) inhibited both LSBs and SSBs. DF594 (0.06-2 mumol/kg) dose-dependently inhibited both migrating LSBs and SSBs. The three antimuscarinic agents, at doses that inhibited colonic spike activity by approximately 80% (equiactive doses), behaved as follows on heart rate and pupil diameter: atropine induced tachycardia and mydriasis, telenzepine had no effect, and DF594 induced slight mydriasis with no effect on heart rate. We conclude that spontaneous motility in the rabbit proximal colon depends on a muscarinic excitatory input. M3 receptors are involved in the control of both LSBs and SSBs, while M1 receptors play an important role in the regulation of LSBs. The development of selective antimuscarinic drugs, acting on a given motility pattern and with minimal side effects, may offer new perspectives in the treatment of functional bowel motor disorders. PMID- 1425076 TI - Hyperammoniemic coma in a patient with ureterosigmoidostomy and normal liver function. AB - Hyperammoniemic encephalopathy has been reported after ureterosigmoidostomy. Its development is related to a problem of bacterial overgrowth and, most often, is favored by the presence of an underlying liver dysfunction. We report the case of a 43-year-old woman with a ureterosigmoidostomy done 28 years earlier who developed hyperammoniemic coma induced by an acute rectocolitis and in the absence of any detectable liver dysfunction. Neither administration of Lactilol and neomycin nor rectal tube drainage were effective; systemic antimicrobial therapy effective against the urease-producing gram-negative bacilli was required and led to a decrease in serum ammonia levels and a dramatic clinical improvement. PMID- 1425077 TI - Interferon therapy is effective in treatment of hepatitis B-induced polyarthritis. AB - A patient with acute hepatitis B developed significant polyarthritis. After 10 months of observation he had not cleared the virus and continued to have symptomatic joint problems, with migratory polyarthralgia, tenosynovitis of the left wrist, and a large knee effusion. Hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA levels were measured in the synovial fluid and were found to be virtually identical to serum levels, indicating the potential infectivity of this fluid. The patient was treated with 14 weeks of thrice-weekly lymphoblastoid interferon and cleared all markers of viral replication. The arthritis resolved with the disappearance of measurable HBsAg. Interferon may be effective therapy for this disorder. PMID- 1425078 TI - Acquired intrahepatic portal vein aneurysm. PMID- 1425079 TI - Acalculous acute cholecystitis due to Salmonella typhi. PMID- 1425082 TI - Esophageal ulcer due to ingestion of melted copper. AB - We report a patient with esophageal stricture as a result of the accidental swallowing of melted copper by a 49-year-old male. As a result, esophagogastric ulcers developed and left a cicatrical stricture. The patient could only manage to swallow liquid food. Radiology of the upper gastrointestinal tract showed marked stricture of the esophagus from the middle thoracic portion to the esophagogastric junction and shortening of the lesser curvature of the stomach. The patient underwent a single-session total gastrectomy, and excision of the thoracic esophagus and construction of anterior thoracic esophagocolic and duodenocolic anastomoses were performed by right thoracotomy and laparotomy, respectively. Macroscopic findings of the surgical specimens showed extensive circular ulcers at the esophagus, and microscopic findings showed deep ulcers extending to the muscle layer with marked fibrosis. The postoperative course was uneventful. PMID- 1425080 TI - Peritoneal sarcoidosis. An unrecognized cause of sclerosing peritonitis. AB - In a Caucasian woman with a history of ocular and pulmonary sarcoidosis, the occurrence of sclerosing peritonitis with exudative ascites but without any of the well-known causes of this syndrome prompts us to consider that sclerosing peritonitis is a manifestation of sarcoidosis. The dramatic improvement that occurred on corticosteroid therapy adds credibility to this previously unreported association. PMID- 1425081 TI - Reversible achalasia-like motor pattern of esophageal body secondary to postoperative stricture of gastroesophageal junction. AB - Two cases are presented of benign stenosis of the cardia secondary to fibrosis following antireflux surgery in which the patients developed a motor alteration in the esophageal body similar to that of achalasia of the cardia. There was a complete absence of contractions in one patient, which had developed over a long period of time, and a vigorous pattern in the other patient, which had evolved over a short period. In both cases, after surgical treatment of the stenosis, normal motility in the esophageal body returned. PMID- 1425083 TI - Hyperfibrinogenemia. An important risk factor for vascular complications in diabetes. AB - OBJECTIVE: To evaluate the determinants of elevated fibrinogen levels and the impact of hyperfibrinogenemia on vascular complications in diabetes. RESEARCH DESIGN AND METHODS: Plasma fibrinogen, glucose, HbA1, and lipids were measured in 116 ambulatory type I and type II diabetic patients with (n = 59) or without (n = 57) clinical evidence of micro- or macrovascular complications. In 56 of these patients, factor VII activity and CRP also were measured. Univariate and multivariate data analyses were conducted. RESULTS: Overall mean +/- SE fibrinogen levels in patients (339 +/- 7.3 mg/dl) were elevated markedly compared with control subjects (248 +/- 9.1 mg/dl). Fibrinogen levels were elevated disproportionately in patients with type II diabetes (P less than 0.0001), hypertension (P = 0.0001), obesity (P less than 0.0001), and vascular complications (P less than 0.0001). Fibrinogen was correlated significantly with age (P less than 0.001), cholesterol (P = 0.002), CRP (P less than 0.001), and factor VII activity (P = 0.032), but not with plasma glucose, triglycerides, HDL cholesterol, or disease duration. Stepwise multiple regression analyses revealed that type II diabetes and presence of vascular complications were major determinants of fibrinogen. For vascular complications, fibrinogen emerged as one of only three independent predictors, the other two being diabetes duration and hypertension. PMID- 1425084 TI - Relationship of fetal macrosomia to maternal postprandial glucose control during pregnancy. AB - OBJECTIVE: To determine the gestational ages at which maternal hyperglycemia is most closely related to fetal macrosomia; to determine whether macrosomia is related to elevations of fasting glucose, postprandial glucose, or both; and to assess the relationship of macrosomia to maternal insulin dose and caloric intake. RESEARCH DESIGN AND METHODS: One hundred eleven consecutive pregnant women with Class B through RF diabetes were studied longitudinally from 13 to 36 wk gestation. Macrosomia was defined by birthweight greater than 90th percentile for gestational age based on California norms. Women who delivered macrosomic infants were compared with those without macrosomic infants on pre- and postprandial blood glucose, GHb, insulin dose, macronutrient intake, and several other maternal variables. RESULTS: Macrosomia occurred in 32 (29%) cases, although several measures indicated reasonable glycemic control throughout pregnancy. Women delivering macrosomic infants did not differ from those without macrosomic infants in maternal age, prepregnant weight, duration of diabetes, White class, macronutrient intake, GHb, or fasting glucose. Macrosomia was associated with higher postprandial glucose levels up to 32 wk gestation and lower insulin doses from 29 to 36 wk gestation. In multiple logistic regression, macrosomia was significantly associated with postprandial glucose only between 29 and 32 wk gestation. Postprandial glucose values less than 7.3 mM (less than 130 mg/dl) were associated with a higher risk of small-for-gestational-age infants (18%) compared with values above this level (1%). CONCLUSIONS: Because macrosomia was related to postprandial glucose but not fasting glucose, we conclude that postprandial glucose measurement should be a part of routine care for diabetes in pregnancy. A target 1-h postprandial glucose value of 7.3 mM (130 mg/dl) may be the level that optimally reduces the incidence of macrosomia without increasing the incidence of small-for-gestational-age infants. PMID- 1425085 TI - Effect of insulin therapy on blood pressure in NIDDM patients with secondary failure. AB - OBJECTIVE: To assess the effect of insulin therapy on blood pressure in NIDDM patients with secondary failure. RESEARCH DESIGN AND METHODS: The influence of insulin treatment on blood pressure was assessed retrospectively in a group of 80 NIDDM patients with secondary failure to diet and maximum doses of oral hypoglycemic agents. Weight, blood glucose, and blood pressure were recorded over a 3-mo period before and after the initiation of insulin therapy. RESULTS: There was a significant rise in systolic (131.8 +/- 1.7 to 148 +/- 1.9 mmHg, P less than 0.05) and diastolic (80.9 +/- 0.9 to 89.2 +/- 1.0 mmHg, P less than 0.02) blood pressures with insulin treatment. Insulin treatment was associated with a significant decrease in blood glucose (18.36 +/- 0.28 to 10.4 +/- 0.34 mM, P less than 0.01) and an increase in weight (72.1 +/- 1.6 to 78 +/- 1.7 kg, P = 0.01). A control group of 80 NIDDM patients matched for age, weight, BMI, and duration of diabetes demonstrated no significant change in blood pressure over a matched period of follow-up. CONCLUSIONS: This study has shown that insulin therapy is associated with significant elevation of both systolic and diastolic blood pressures. PMID- 1425086 TI - Lack of effects of hypoglycemia on glucose absorption in healthy men. AB - OBJECTIVE: To assess the effects of hypoglycemia on glucose absorption by examining the systemic appearance of 3-OMG (a glucose analogue that is transported by the same mechanism as glucose) after oral administration. RESEARCH DESIGN AND METHODS: Six healthy males 22-31 yr of age were studied during a hypoglycemic (50 mg [2.7 mM]/100 ml) and a euglycemic (90 mg [5.0 mM]/100 ml) glucose clamp. At 50 min after exposure to insulin, an oral glucose load containing 20 g of glucose and 4.5 g of 3-OMG dissolved in 300 ml of tap water was administered. Insulin administration was interrupted 30 min after oral glucose administration. RESULTS: Plasma glucose was clamped at 88 +/- 1.3 mg (4.9 +/- 0.1 mM)/100 ml during euglycemia and at 50 +/- 1.9 mg (2.7 +/- 0.1 mM)/100 ml during hypoglycemia. Concentrations of glucagon, growth hormone, cortisol, and epinephrine were significantly elevated during hypoglycemia. After 60 min, circulating 3-OMG concentrations increased to zeniths of 11.4 +/- 0.2 mg (585 +/- 10.0 mM)/100 ml (hypoglycemia) and 11.6 +/- 1.1 mg (585 +/- 56.0 microM)/100 ml (euglycemia; P = 0.95). Absorption of 3-OMG was evident between 15 and 20 min after administrations in both situations. Serum insulin was significantly lower during hypoglycemia compared with the control situation (345 +/- 50 microM [hypoglycemia], 445 +/- 50 microM [euglycemia], P = 0.03). CONCLUSIONS: We conclude that hypoglycemia does not seem to affect intestinal absorption of glucose as judged by systemic appearance of 3-OMG. PMID- 1425087 TI - Physical activity and proliferative retinopathy in people diagnosed with diabetes before age 30 yr. AB - OBJECTIVE--To examine the relationships of past and current physical activity to the prevalence of PDR. RESEARCH DESIGN AND METHODS--Individuals diagnosed with diabetes less than 30 yr of age (n = 818), who were participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were examined during 1984-1986. Stereoscopic fundus photographs were graded for presence of PDR. Physical activity was assessed by an interviewer-administered standardized questionnaire. RESULTS--Women diagnosed with diabetes less than 14 yr of age who reported a history of participation in team sports in high school or college were less likely to have PDR at examination (OR 0.46, 95% CI 0.23, 0.93). Those women who reported current strenuous activity levels were less likely to have PDR (OR 0.34, 95% CI 0.13, 0.87). There were no significant associations between past or current physical activity and PDR in men. Current levels of energy expenditure were not related to PDR in either sex. CONCLUSIONS- Higher levels of physical activity may be associated with a reduced risk of having PDR in women. However, the lack of similar findings in men suggests that physical activity may be a relatively unimportant factor in the etiology of PDR. PMID- 1425088 TI - Permanent diabetes without serological evidence of autoimmunity after transient neonatal diabetes. AB - OBJECTIVE: To describe a probable association between TNDM and subsequent permanent IDDM. RESEARCH DESIGN AND METHODS: A longitudinal follow-up of a single case from birth to 12 yr of age was conducted analyzing sequential OGTTs, ICAs, AIAs, anti-GAD antibodies, and other organ-specific and nonspecific antibodies. RESULTS: A small-for-gestational-age infant developed hyperglycemia at 20 h of age and required insulin therapy for the 1st 14 wk of life (TNDM). Transient hyperglycemia and ketonuria were noted again at age 2 yr 10 mo during an intercurrent illness, but OGTT was normal; and ICA, AIA, anti-GAD65 and anti GAD67 antibodies, antithyroid microsomal, anti-gastric parietal cell, antiadrenal, antisteroidal, and antinuclear antibodies were negative 3 wk later. At age 9 yr, hyperglycemia returned and persisted in the setting of hypoinsulinemia; ICA, AIA, anti-GAD65 and anti-GAD67 antibodies, and other organ specific and nonspecific antibodies were again negative. Insulin therapy was initiated and has been maintained over 3 yr of follow-up. CONCLUSIONS: Our case is the fifth reported with permanent diabetes occurring after resolution of TNDM. The etiology of permanent diabetes in this setting is unknown but, unlike classical IDDM, appears unrelated to autoimmunity in our patient. The true frequency of this association remains unknown. PMID- 1425089 TI - Greater effect of glycemia on incidence of hypertension in women than in men. AB - OBJECTIVE: In subjects with NIDDM, diabetic women have a greater relative excess of CHD relative to nondiabetic women than do diabetic men relative to nondiabetic men. This excess in diabetic women is explained partially by the particularly atherogenic pattern of lipoproteins in this group. We hypothesize that diabetic women also may have a higher incidence of hypertension than diabetic men. RESEARCH DESIGN AND METHODS: We examined the effect of NIDDM and IGT relative to NGT on the incidence of hypertension separately in men (n = 844) and women (n = 618) in the 8-yr follow-up of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. RESULTS: Women had a greater risk of hypertension with worsening glucose tolerance (RR NIDDM/NGT = 2.65 and RR IGT/NGT = 1.94) compared with men (RR NIDDM/NGT = 1.61 and RR IGT/NGT = 0.91). Controlling for other possible confounding variables such as age, obesity, body fat distribution, and fasting insulin concentration did not alter the interaction of sex and glycemia on incidence of hypertension. CONCLUSIONS: The especially increased risk of hypertension in women with abnormal glucose tolerance may explain partly the high risk of CHD in this group. PMID- 1425090 TI - Dyslipidemias among normoglycemic members of familial NIDDM pedigrees. AB - OBJECTIVE: To examine the hypothesis that hyperinsulinemia among relatives of NIDDM probands will increase the prevalence of DLPs, we measured insulin levels and examined the frequency of DLPs among NIDDM pedigree members. RESEARCH DESIGN AND METHODS: We performed 2-h 75-g OGTTs and measured lipid and insulin levels of 287 family members and 86 spouses from 16 large Utah pedigrees ascertained for greater than or equal to 2 siblings with NIDDM. RESULTS: One-hour insulin levels were higher among 206 family members with NGT than among 65 NGT spouses (483.3 vs. 361.7 pM, P = 0.05). Among the NGT family members, 32% had cholesterol levels at or above the age- and sex-specific 90th percentile level defined by the LRC studies, 33% had HDL levels less than or equal to 10th percentile, and 20% had triglyceride levels greater than or equal to 90th percentile. DLP (any of the three abnormalities) was found among 58% of NGT family members, which was significantly higher than the expected 27% (P less than 0.00001) and the prevalence among spouses of 45% (P less than 0.05). By NCEP criteria for hyperlipidemia, 40% of family members met criteria for diet and/or pharmacological therapy. CONCLUSIONS: Normoglycemic members of NIDDM pedigrees have a high prevalence of DLPs, which approaches the prevalence in patients with NIDDM. Our data suggest that members of NIDDM pedigrees should be screened carefully for lipid abnormalities. PMID- 1425091 TI - Prevalence of carotid atherosclerosis in diabetic patients. Ultrasound high resolution B-mode imaging on carotid arteries. AB - OBJECTIVE: To quantitatively assess atherosclerosis of the carotid artery in subjects with and without diabetes. RESEARCH DESIGN AND METHODS: Ultrasound high resolution B-mode imaging of carotid arteries was conducted on 71 nondiabetic subjects without hyperlipidemia or hypertension and 295 diabetic patients to determine IMT of the arterial wall. RESULTS: IMT was linearly related with age in nondiabetic (IMT = [0.0087 x age] + 0.3318) and diabetic subjects (IMT = [0.0155 x age] + 0.32450). The regression coefficient for age was significantly greater in diabetic than nondiabetic subjects. IMT (mean +/- SD) of diabetic subjects aged 20-29 was significantly greater than that of nondiabetic subjects aged 20-29 (0.73 +/- 0.27 vs. 0.52 +/- 0.07 mm, P less than 0.01). Multivariate regression analysis of 275 NIDDM patients indicated smoking, hyperlipidemia, duration of diabetes, hypertension, and age were factors determining thickness of the carotid arterial wall. CONCLUSIONS: Diabetes, along with age, hyperlipidemia, smoking, and hypertension, aggravates carotid atherosclerosis. PMID- 1425092 TI - Insulin action in black Americans with NIDDM. AB - OBJECTIVE: To assess the influences that obesity and hyperglycemia have on insulin action in black NIDDM patients. RESEARCH DESIGN AND METHODS: Thirty-nine subjects were studied who had normal GHb levels and/or FPG less than 6.4 mM and who had not taken pharmacological agents for 2-91 mo before the study. Insulin action was studied using the euglycemic insulin clamp with a D-[3-3H]glucose infusion. Degree of obesity was assessed with BMI. During carefully monitored follow-up, 9 patients relapsed into a hyperglycemic state, and insulin action was restudied after acute reregulation of their plasma glucose. RESULTS: Insulin action was related to the degree of obesity at the extremes of BMI: 7 of 8 patients (87.5%) with a BMI less than 24.0 kg/m2 were insulin sensitive, and 8 of 9 patients (88.9%) with a BMI greater than 28.5 kg/m2 were insulin resistant. In the midrange BMI (24.0-28.5 kg/m2), patients were equally likely to be insulin resistant or insulin sensitive. A plot of frequency versus glucose disposal in those patients was compatible with a bimodal distribution (P less than 0.025): 12 of 22 patients were normally insulin sensitive (glucose disposal 6.1-9.4 mg.kg 1.min-1), and 10 were insulin resistant (glucose disposal 2.4-4.8 mg.kg-1.min-1). Analysis of this midrange BMI group showed that in the insulin-sensitive group, an inverse relationship existed between BMI and glucose disposal (r = -0.64, P less than 0.05), whereas no such relationship was found in the insulin-resistant group. The clinical characteristics of the midrange BMI group indicated that fasting plasma insulin, total cholesterol, and triglycerides were higher; whereas BMI, age, and FPG were not different in the insulin-resistant compared with the insulin-sensitive group. With the development of hyperglycemia, insulin action in the insulin-sensitive group. With the development of hyperglycemia, insulin action in the insulin-sensitive group was decreased, independent of obesity, whereas it was unchanged in the insulin-resistant group. CONCLUSIONS: Insulin resistance exists in only approximately 50% of black NIDDM patients. The relationship between obesity and insulin resistance is not a simple one. The data can be explained by one of two hypotheses: 1) insulin resistance in black NIDDM patients is an acquired defect related to the development of obesity and is modulated by hyperglycemia, or 2) NIDDM exists as two variants, one with primary insulin resistance and one with normal insulin sensitivity, and that insulin resistance causes central and/or generalized obesity. PMID- 1425094 TI - Prevalence and clinical picture of IDDM in Nigerian Igbo schoolchildren. AB - OBJECTIVE: To evaluate the prevalence and clinical picture of IDDM in Nigerian Igbo schoolchildren born and living in continental Africa. RESEARCH DESIGN AND METHODS: In three school districts (Ezza, Ishielu, Ohaukwu), 77,862 schoolchildren aged 5-17 yr answered our questionnaires on age, sex, known disease, drugs being taken, family history, and diabetic symptoms like polyuria, polydipsia, polyphagia, and weight loss. Positive respondents were given glucosuric tests, and glucosuric subjects had hyperglycemic tests. Diagnosis of IDDM was established in hyperglycemic patients by referred hospital clinicians based on insulin requirements. RESULTS: Twelve new cases of IDDM were found in addition to 14 previously diagnosed cases, giving a CPR of 0.33/1000. Ishielu had a CPR of 0.46/1000 compared with 0.25 (P less than 0.01) for Ohaukwu. Boys had a CPR of 0.38/1000 compared with 0.25/1000 (P less than 0.06) for girls. Boy-to girl prevalence ratio was approximately 3:1. CONCLUSIONS: The relatively high prevalence of IDDM in this poor African population, despite potential deaths caused by minimal medical attention, may be because of long-term protein malnutrition and endemic childhood infections, which have been implicated in the etiology of IDDM in similar malnourished populations. PMID- 1425093 TI - Clinical characteristics of IDDM in Hispanics and non-Hispanic whites. Little evidence of heterogeneity by ethnicity. AB - OBJECTIVE: To compare the clinical characteristics of IDDM in HD and NHWD subjects in order to evaluate potential heterogeneity of IDDM by ethnicity. RESEARCH DESIGN AND METHODS: HD subjects (n = 73) and NHWD subjects (n = 97) were recruited from the Colorado IDDM Registry. The registry included individuals who were Colorado residents, less than 18 yr old at diagnosis, placed on insulin within 2 wk of diagnosis, and had diabetes not secondary to other conditions. Residual beta-cell function was measured as the 1-h C-peptide response to a Sustacal challenge. RESULTS: HD subjects were similar to NHWD subjects in insulin dose, HbA1, HLA-DR antigens, ICAs, and family history of IDDM. HD subjects were more likely to have a family history of NIDDM than NHWD subjects (11 vs. 3%, P = 0.03). HD girls had higher C-peptide levels (0.27 vs. 0.11 nm/L [0.83 vs. 0.33 ng/ml], P = 0.01), BMI (22.7 vs. 20.9 kg/m2 P = 0.04), subscapular skinfold thickness (18.9 vs. 15.0 mm, P = 0.04), and WHR (0.81 vs. 0.77, P = 0.03) than NHWD females. After controlling for diabetes duration, BMI, sex, and family history of NIDDM, residual beta-cell function was associated significantly with Hispanic ethnicity, although the term accounted for just 3% of the overall variability in C-peptide levels. CONCLUSIONS: Little evidence of heterogeneity by ethnicity of IDDM patients in the Colorado IDDM Registry was found. Ethnic differences in C-peptide levels may be related to differences in body fat distribution in females rather than heterogeneity of the disease. PMID- 1425095 TI - Standardization of IVGTT to predict IDDM. AB - OBJECTIVE: To review current practice in centers that use the IVGTT for prediction of IDDM. To establish consensus protocol for performance of the test. RESEARCH DESIGN AND METHODS: Postal questionnaires were delivered to 12 centers. RESULTS: Eleven centers used a glucose dose of 0.5 g/kg and 1 used 0.3 g/kg; the dosage in adults was limited to a maximum of 25-50 g in some centers but others applied no upper limit. The glucose concentration of the infusate varied between 20 and 66%. Eight centers injected glucose manually, two used a syringe pump, and two used gravity infusion. The period of infusion ranged from 30 +/- 10 s to 4 +/ 2 min, and time zero was taken as the start (1 center), middle (1 center), or end (10 centers) of the infusion. The potential range in timing of the +1-min sample varied between 1 and 7 min from the start of the infusion. Quality assurance standards for the insulin assays used were not always appropriate for the fasting and low stimulated range of insulin levels. CONCLUSIONS: The first phase insulin response to the IVGTT is widely measured as an index of risk of progression to IDDM. We established that methodology varies widely. Because of this, a new standard protocol for use in prediction of IDDM was agreed by an ICARUS working group and is described herein. PMID- 1425096 TI - High incidence rate of IDDM in Sardinia. Sardinian Collaborative Group for Epidemiology of IDDM. AB - OBJECTIVE: To provide reliable data on the incidence of IDDM in Sardinia and contribute to a better understanding of its geographical variability throughout Europe. RESEARCH DESIGN AND METHODS: All newly diagnosed cases of IDDM with onset less than 30 yr of age between 1 January 1989 and 31 December 1990 among residents in Sardinia were recorded. Primary ascertainment was based on notification by all Sardinian hospitals, outpatient clinics, family doctors, and pediatricians. The local IDDM patient association served as the secondary and independent source. RESULTS: The completeness of ascertainment was 92.8%. The annual incidence rate of IDDM (per 100,000) over the 2-yr period was 30.7 in the 0-14-yr-old age-group and 24.1 in the entire 0-29-yr-old range, respectively, with no significant differences between the two groups. Male/female ratios were 1.25 and 1.55, respectively. No significant seasonal variation in incidence was observed. CONCLUSIONS: Sardinia appears to have the second-highest IDDM incidence rate in Europe after Finland, and the island contradicts the generally accepted rule of a south-to-north incidence gradient. PMID- 1425097 TI - Insulin requirements in insulin-dependent and insulin-requiring GDM women during final month of pregnancy. AB - OBJECTIVE: To determine the significance of falling insulin requirements after the 36th wk of gestation in insulin-requiring pregnant women. RESEARCH DESIGN AND METHODS: Insulin requirements of women with IDDM and IRGDM were assessed from the 36th wk of pregnancy, with evaluation of maternal characteristics and fetal outcomes. RESULTS: In 32 pregnancies of women with IDDM, there was a 5 +/- 2% decrease in insulin requirements, and in 19 pregnancies of women with IRGDM, there was a 28 +/- 10% increase. Of the 62% of women whose insulin requirements declined, the decrement was 12 +/- 2% and was associated with longer duration of diabetes (12 +/- 2 vs. 6 +/- 1 yr, P less than 0.05) but not with age, prepregnancy BMI, weight gain, or maternal or fetal complications. Only 3 pregnancies in IRGDM women were associated with a decrease in insulin requirements. Although maternal parameters were no different from those with IDDM, infants born to women with IRGDM were smaller (3531 +/- 123 vs. 3874 +/- 94 g, P less than 0.005). CONCLUSIONS: Insulin requirements from the 36th wk of gestation commonly decreased in women with IDDM, associated with longer duration of diabetes but did not carry any adverse prognostic indication for the infants. Women with IRGDM experienced a continual increase in insulin requirements over the final weeks of pregnancy. PMID- 1425098 TI - Relationship of postload plasma glucose to mortality with 19-yr follow-up. Comparison of one versus two plasma glucose measurements in the Chicago Peoples Gas Company Study. AB - OBJECTIVE: To explore the relationship of one versus two postload plasma glucose measurements to 19-yr mortality in men in the Chicago Peoples Gas Company Study. RESEARCH DESIGN AND METHODS: One-hour postload plasma glucose was measured twice (1.4 yr apart, 1965-1967) for 873 nondiabetic men 34-65 yr of age. Serum cholesterol, blood pressure, height, and weight were measured. Data on smoking habits were obtained. Mortality follow-up was complete through July 1986, 19 yr after second glucose load. RESULTS: In prospective analyses, with each of three glucose values--first, second, and mean of first and second--coronary, cardiovascular, and all-cause age-adjusted mortality rates were higher in quintiles 3, 4, and 5 compared with quintile 1, with a significant linear trend. Multivariate analyses with glycemia as a continuous variable confirmed a positive independent association between plasma glucose and mortality endpoints with first measurement and mean of two values but not with second. With dichotomization of plasma glucose (greater than or equal to 11.2 mM [greater than or equal to 200 mg/dl]) for 30 men hyperglycemic both times, CHD and CVD death rates were significantly higher (odds ratios 2.3-2.7) compared with those for 758 men consistently nonhyperglycemic. In contrast, for those hyperglycemic once only, death rates were not significantly higher. Results of multivariate analyses were consistent with these findings. CONCLUSIONS: These data indicate a significant relationship of asymptomatic hyperglycemia on repeat examinations to coronary and cardiovascular mortality independent of other factors measured in the study. PMID- 1425099 TI - C-peptide response to meal challenge in nondiabetic and diabetic adults living in Wadena, Minnesota. AB - OBJECTIVE: The goal of the study was to provide cross-sectional descriptive data on the response of C-peptide to a vigorous meal stimulus in a population-based sample of nondiabetic adults compared with a population-based sample of adults with NIDDM. Available information is scanty, especially in subjects greater than 50 yr old. RESEARCH DESIGN AND METHODS: The group under study included 377 adults without previously known diabetes randomly chosen from the population of the city of Wadena, Minnesota, almost all of northern European background, and 88 adults with known diabetes. PCP was measured 90 min after ingestion of 480 ml liquid meal Ensure-Plus, which includes 95 g dextrose, 26 g protein, and 25 g fat. C peptide also was measured in a 260-min urine collection after the meal challenge. Novo antibody M1221 was used for C-peptide assay throughout the study. Participants whose medical record indicated insulin-dependent diabetes with a history of acetone production were excluded from analyses. RESULTS: The distribution of UCP and PCP in this group of subjects appears very broad. Both the highest and lowest values for C-peptide were observed in individuals with diabetic glucose tolerance. The mean and median values in the nondiabetic group are higher than in previously published reports. After statistical adjustment for age, sex, BMI, and concomitant plasma glucose, participants with IGT produced significantly more C-peptide than the group with NGT (3.48 vs. 2.96 nM PCP, P less than 0.05). Participants with diabetic glucose tolerance and who were not taking insulin produced as much or more C-peptide than either the NGT or IGT groups, depending on the statistical model used for adjusting for plasma glucose. Diabetic participants who were taking insulin produced significantly lower amounts of C-peptide than any of the non-insulin-taking groups (approximately 30% of the C-peptide produced by the non-insulin-taking diabetic participants). A decline in PCP production with increasing years since diagnosis (5.7%/yr) was observed exclusively in the insulin-taking NIDDM participants. Effect modification by glucose tolerance classification was observed on the relationship between plasma glucose and PCP: PCP increased with increasing plasma glucose in NGT and IGT groups, but a nonsignificant negative relationship was exhibited in diabetic participants. CONCLUSIONS: The data suggest that two forms of NIDDM may exist, crudely distinguished by the clinical decision to use insulin to control blood glucose levels. The insulin-taking diabetic individuals may experience a greater likelihood of pancreatic failure, whereas non-insulin-taking diabetic individuals probably experience stable pancreatic function over the course of their disease. Longitudinal observation of the Wadena cohort will provide more insight into this possibility. PMID- 1425100 TI - Prevalence of glucose intolerance in Asian Indians. Urban-rural difference and significance of upper body adiposity. AB - OBJECTIVE: To evaluate the prevalence of NIDDM and IGT in the urban and rural areas in southern India. RESEARCH DESIGN AND METHODS: Two populations of the same ethnic background, but different socioeconomic background were chosen for this study. Nine-hundred urban people and 1038 rural subjects were studied. Fasting and 2-h post-glucose capillary blood samples after a 75 g oral glucose load (WHO criteria) were obtained in these randomly selected adults (greater than or equal to 20 yr of age). RESULTS: Using the WHO criteria, the prevalence of NIDDM, adjusted to the age of the respective general population, was 8.2% in the urban and 2.4% in the rural populations. The prevalence was 8.4 and 7.9%, respectively, in urban men and women, and 2.6 and 1.6% in rural men and women. The age-adjusted prevalence of IGT was 8.7 and 7.8% in the urban and rural areas, respectively. The prevalence of IGT was 8.8% in urban men and 8.3% in women; the corresponding values for rural men and women were 8.7 and 6.4%. The prevalence of NIDDM increased with age, markedly so in the urban people. The urban-rural difference was significant for NIDDM (chi 2 = 29.4, P less than 0.001) but not for IGT. In the urban population, 65% of the NIDDM patients were known cases, whereas in the rural area, the known cases accounted for only 24%. Bivariate analysis showed an association of BMI, STR, and WHR with prevalence of NIDDM plus IGT. In the multiple logistic regression analysis, age, BMI, STR, and WHR were associated significantly with glucose intolerance in the urban population, whereas only age was significant in the rural population. The best predictors of NIDDM were age, BMI, WHR, and urbanization. CONCLUSIONS: The study showed a high prevalence of NIDDM in the urban southern Indian population. The prevalence of NIDDM in the same ethnic group in rural areas was significantly lower. The prevalence of IGT was similar in both populations. Upper body adiposity was a significant predictor of NIDDM in this population with low rates of obesity. PMID- 1425101 TI - Eating disorders in adolescents with IDDM. A controlled study. AB - OBJECTIVE: To determine the prevalence of clinical eating disorders and lesser degrees of disturbed eating in adolescents with IDDM and a matched sample of nondiabetic control subjects. RESEARCH DESIGN AND METHODS: A cross-sectional survey of eating habits and attitudes conducted in 76 adolescents with IDDM, and age- and sex-matched nondiabetic control subjects. Eating disorder features were assessed by standardized research interview adapted for use with patients with diabetes (EDE). Glycemic control was assessed by GHb assay. RESULTS: Adolescent girls with IDDM were heavier than nondiabetic female control subjects and were dieting more intensively to control their shape and weight. However, clinical eating disorders were no more common among adolescent girls with IDDM than among nondiabetic control subjects. Nine percent of the IDDM girls met diagnostic criteria for an operational version of "Eating disorder not otherwise specified." Fifteen percent had omitted or reduced their dose of insulin to influence their shape and weight. Eating disorder features and insulin misuse for shape and weight control were not found in IDDM or nondiabetic boys, and these two groups did not differ in their body weight. CONCLUSIONS: Adolescent girls with IDDM are heavier than their nondiabetic counterparts and diet more intensively to control their shape and weight. Disordered eating habits and weight control behavior are common, but no more so in IDDM than in nondiabetic subjects. Insulin misuse for the purpose of shape and weight control is not restricted to subjects with a clinical eating disorder. Disordered eating is associated with impaired glycemic control. PMID- 1425102 TI - Prevalence of eating disorder symptoms in preadolescent and adolescent girls with IDDM. AB - OBJECTIVE: To assess attitudinal and behavioral symptoms of eating disorders in preadolescent and adolescent girls with IDDM and a matched sample of nondiabetic subjects, and to explore the relationship between the perceived impact of IDDM and eating disorder symptoms. RESEARCH DESIGN AND METHODS: All eligible IDDM patients (girls, age 8-18 yr) from the case register of the Yale Children's Diabetes Clinic were recruited for this study. Of 49 eligible patients, 46 participated in the study. Control subjects were recruited among students in several local schools; 46 girls, individually age and race-matched with IDDM patients, and group-matched by father's socioeconomic status, were included in this study. All subjects participated in an investigator-based clinical interview (EDE) and completed a self-report measure of eating-related psychopathology (EDI). IDDM subjects completed the DQOL measure to determine the perceived impact of diabetes on patients' lives. RESULTS: IDDM patients reported significantly more regular consumption of meals and snacks than did nondiabetic subjects. No group differences were found on measures of symptoms of eating disorders: both groups reported minimal levels of symptoms. Among adolescent IDDM patients, eating disorder symptoms were related significantly to patients' dissatisfaction with the illness and its impact on their lives. CONCLUSIONS: It appears that when applying stringent diagnostic procedures and matching criteria, IDDM girls do not evidence an elevated prevalence of eating disorder symptoms. However, those IDDM patients who did report symptoms may be a high-risk group for the development of an eating disorder and should be followed prospectively. PMID- 1425103 TI - Cost-effectiveness of alternative methods for diabetic retinopathy screening. AB - OBJECTIVE: To assess from the perspectives of a government delivery system and patients, the cost-effectiveness of the 45-degrees retinal camera compared to the standard ophthalmologist's exam and an ophthalmic exam by a physician's assistant or nurse practitioner technician, for detecting nonproliferative and proliferative diabetic retinopathy. RESEARCH DESIGN AND METHODS: Comparison of 45 degrees fundus photographs with and without pharmacological pupil dilation taken by technicians and interpreted by experts, direct and indirect ophthalmoscopy by ophthalmologists, and direct ophthalmoscopy by technicians with seven-field stereoscopic fundus photography (reference standard). Costs were estimated from market prices and actual resource use. The study included 352 patients attending outpatient diabetes and general-medicine clinics at VA and DOD facilities. RESULTS: Medical system costs per true positive were: 45-degrees photos with dilation, $295; 45-degrees photos without dilation, $378; ophthalmologist, $390; and technician, $794. Patient costs per true positive were: 45-degrees photos with dilation, $139; 45-degrees photos without dilation, $171; ophthalmologist, $306; and technician, $1009. Cost-effectiveness is sensitive to program size due to high fixed cost of the camera methods but not to prevalence. Cost effectiveness of the technician exam is strongly affected by its sensitivity. CONCLUSIONS: Primary-care screening with retinal photographs through pharmacologically dilated pupils for diabetic retinopathy is an appropriate and cost-effective alternative to screening by an ophthalmologist in this setting. Ophthalmologists are scarce, primary-care physicians are extremely busy, and large clinics allow fixed equipment costs to be spread across many patients. PMID- 1425104 TI - Diabetes is not caused by cassava toxicity. A study in a Tanzanian community. AB - OBJECTIVE: To test the hypothesis that consumption of cassava with liberation of cyanide causes diabetes in malnourished individuals. RESEARCH DESIGN AND METHODS: Glucose tolerance was assessed in two rural communities in Tanzania; in one (Nyambori), the main source of calories was cassava; and in the other (Uswaa), cassava was rarely eaten. Undernutrition was prevalent in both communities. The people of Nyambori were known to have high dietary cyanide exposure for many years from consumption of insufficiently processed cassava. Of the 1435 people in Nyambori greater than or equal to 15 yr old, 1067 (74%) were surveyed, and 1429 of 1472 (97%) eligible subjects in Uswaa were surveyed. All had 75-g oral glucose tolerance tests and measurement of BMI. Plasma and urine thiocyanate and blood cyanide also were measured in some subjects. RESULTS: Mean +/- SD plasma and urine thiocyanate levels in Nyambori were 296 +/- 190 and 497 +/- 457 microM (n = 204), respectively, compared with 30 +/- 37 and 9 +/- 13 microM, respectively, in Uswaa (n = 92) (P less than 0.001 for all differences). The mean blood cyanide level in Nyambori was elevated (1.4 [range 0.1-30.2] microM; n = 91). The prevalence of diabetes in the cassava village (Nyambori) was 0.5% compared with 0.9% in Uswaa (NS). The prevalence of IGT was similar in the two villages in the 15- to 34- and the 34- to 54-yr-old age-groups; but in those greater than or equal to 55 yr old, IGT was higher in Nyambori (17.4 vs 7.2%, P = 0.029). Mean fasting and 2-h blood glucose levels were slightly higher in Nyambori village after adjusting for age, sex, and BMI (4.5 vs. 4.2 and 5.0 vs. 4.4 mM, respectively). CONCLUSIONS: High dietary cyanide exposure was not found to have had a significant effect on the prevalence of diabetes in an undernourished population in Tanzania. Cassava consumption is thus highly unlikely to be a major etiological factor in so-called MRDM, at least in East Africa. PMID- 1425105 TI - Identifying diabetic patients at high risk for lower-extremity amputation in a primary health care setting. A prospective evaluation of simple screening criteria. AB - OBJECTIVE: To evaluate prospectively a risk categorization scheme for lower extremity problems that incorporates the Semmes-Weinstein 5.07 monofilament and a simple exam to stratify patients who were followed in a primary-care setting into risk groups for plantar ulceration and lower-extremity amputation. RESEARCH DESIGN AND METHODS: Patients with diabetes in a well-defined American-Indian population were stratified into four risk categories based on sensation status to the 5.07 monofilament, the presence of foot deformity, and a history of lower extremity events (amputation or ulceration): category 0, sensate; category 1, insensate; category 2, insensate with deformity; and category 3, history of lower extremity events. Patients were followed prospectively for lower extremity events and changes in sensation status. RESULTS: We gave screening exams to 358 (88%) of 406 individuals with diabetes in the community. The distribution of patients for risk categories 0, 1, 2, and 3 was 74.3, 8.4, 4.5, and 13%, respectively. Over a 32-mo follow-up period, 41 patients developed ulcerations, and incidence rates correlated positively with increasing risk category (P less than 0.00001). All 14 amputations occurred in risk groups 2 and 3. CONCLUSIONS: These data suggest that the risk categorization described here may have a role in identifying patients at risk for lower extremity events who are followed in a primary-care setting. PMID- 1425106 TI - Diabetes mellitus in Alaskan Yup'ik Eskimos and Athabascan Indians after 25 yr. AB - OBJECTIVE: To estimate the prevalence of diabetes mellitus and overweight in two populations of Alaska Natives and to compare the results with previous data. RESEARCH DESIGN AND METHODS: Participants' heights, weights, and random plasma glucose levels were determined. Those with a glucose of greater than or equal to 6.72 mM received a follow-up glucose-tolerance test, interpreted by WHO criteria. Overweight was defined by National Center for Health Statistics criteria and also by criteria used in previous studies. The subjects were Eskimo and Athabascan residents greater than or equal to 40 yr of age in 15 villages in southwestern Alaska. RESULTS: Diabetes prevalence was 4.7% for Eskimos and 10.0% for Indians. Among Eskimo men and women, the prevalence of overweight was 34 and 56%, respectively, among Indian men and women, it was 29 and 55%, respectively. Comparisons with past data indicate that the prevalence of diabetes has increased from 1.7% in 1962 for Eskimos and 1.8% in 1969 for Indians. CONCLUSIONS: The prevalence of diabetes appears to have increased among Eskimos and Indians in Alaska. Overweight appears to be a significant problem in both groups. PMID- 1425107 TI - Growth of children before onset of diabetes. AB - OBJECTIVE: To examine the growth of children before the onset of diabetes. RESEARCH DESIGN AND METHODS: Heights before diagnosis, expressed as SDS, of each diabetic child identified from the diabetes register and of two age- and sex matched control subjects were obtained from records of routine examinations performed at 3.5, 6, 11, and 13 yr. The heights of their siblings, with control subjects, also were obtained. RESULTS: Diabetic children were considerably taller than control subjects before diagnosis (0-1 yr before diagnosis SDS 0.82 +/- 0.26 vs. 0.16 +/- 0.14, P less than 0.05, n = 24; 1-2 yr before diagnosis SDS 1.02 +/- 0.17 vs. 0.16 +/- 0.14, P less than 0.001, n = 30; 2-3 yr before diagnosis SDS 0.97 +/- 0.23 vs. 0.04 +/- 0.20, P less than 0.005, n = 16). At more than 3 yr before diagnosis, the diabetic children were not significantly taller than control subjects (SDS 0.8 +/- 0.2 vs. 0.27 +/- 0.13, respectively; n = 33). The siblings of the diabetic children were no taller than control subjects. CONCLUSIONS: Diabetic children, but not their siblings, were taller than control subjects before diagnosis, suggesting growth-inducing metabolic changes may precede the onset of clinical diabetes by at least 3 yr. PMID- 1425108 TI - Increased plasma endothelin in NIDDM patients with retinopathy. AB - OBJECTIVE: To elucidate the significance of ET in diabetic microvascular disease. RESEARCH DESIGN AND METHODS: We determined plasma levels of ir-ET-1 in 25 NIDDM patients without hypertension and/or renal dysfunction. RESULTS: The plasma levels of ir-ET-1 in NIDDM patients with simple (n = 8) and proliferative (n = 8) retinopathy were 0.58 +/- 0.04 pM and 0.60 +/- 0.04 pM, respectively, which were significantly higher than those in normal, nondiabetic subjects (0.24 +/- 0.02 pM [n = 31]) and NIDDM patients without retinopathy (0.30 +/- 0.05 pM [n = 9]). CONCLUSIONS: These results suggest that plasma ET-1 is related to diabetic microvascular disease. PMID- 1425109 TI - Eating disorders and IDDM. A problematic association. AB - IDDM and eating disorders are common conditions in young women. Whether a specific association exists between these two disorders remains controversial. Some studies have suggested an increased incidence of eating disorders in young women with IDDM, whereas others have not detected such an increase. These differences may be attributable, at least in part, to methodological issues in study design, measurement tools, and relatively small sample sizes. Whether the prevalence of eating disorders in IDDM is increased will be resolved only by larger studies that use standardized diagnostic interviews. We suspect that certain aspects of IDDM and its management may trigger the expression of an eating disorder in susceptible individuals. Required dietary restraint and weight gain related to diabetes management are the factors most likely to be implicated. Eating disorders are relatively common in young women with IDDM and may contribute to impaired metabolic control with hypoglycemia and DKA, and to long term microvascular complications of diabetes. Omission or reduction of required insulin, an extremely common means of weight control in these young women, is likely an important factor in this regard. Further research is required to determine more precisely the relationship between IDDM and eating disorders, and the effects of eating disorders on metabolic control and chronic complications of IDDM. PMID- 1425110 TI - Stress and diabetes mellitus. AB - Stress is a potential contributor to chronic hyperglycemia in diabetes. Stress has long been shown to have major effects on metabolic activity. Energy mobilization is a primary result of the fight or flight response. Stress stimulates the release of various hormones, which can result in elevated blood glucose levels. Although this is of adaptive importance in a healthy organism, in diabetes, as a result of the relative or absolute lack of insulin, stress-induced increases in glucose cannot be metabolized properly. Furthermore, regulation of these stress hormones may be abnormal in diabetes. However, evidence characterizing the effects of stress in type I diabetes is contradictory. Although some retrospective human studies have suggested that stress can precipitate type I diabetes, animal studies have shown that stressors of various kinds can precipitate--or prevent--various experimental models of the disease. Human studies have shown that stress can stimulate hyperglycemia, hypoglycemia, or have no affect at all on glycemic status in established diabetes. Much of this confusion may be attributable to the presence of autonomic neuropathy, common in type I diabetes. In contrast, more consistent evidence supports the role of stress in type II diabetes. Although human studies on the role of stress in the onset and course of type II diabetes are few, a large body of animal study supports the notion that stress reliably produces hyperglycemia in this form of the disease. Furthermore, there is mounting evidence of autonomic contributions to the pathophysiology of this condition in both animals and humans. PMID- 1425111 TI - Evaluating diabetes education. Are we measuring the most important outcomes? AB - This article reviews the published literature on diabetes education evaluations and makes recommendations for outcome measures to be used in future research. We conclude that program evaluations to date have focused too narrowly on assessing knowledge and GHb outcomes to the exclusion of other important variables. To reflect the changing emphasis and conceptual basis of diabetes education, we recommend that future evaluations do the following: 1) report on the program's target population, recruitment methods, and representativeness of participants; 2) collect measures of self-efficacy and patient-provider interaction; 3) include quality of life and patient-functioning outcomes; and 4) use more standardized and objective measures of diabetes management behaviors. We close by providing practical examples of feasible collection measures for most settings and references to studies that have done so. PMID- 1425112 TI - Response to "Topical phenytoin in diabetic foot ulcers". PMID- 1425113 TI - Measuring subjective symptoms. PMID- 1425114 TI - Semantics of plasma glucose thresholds for counterregulatory responses. PMID- 1425115 TI - Difference between islet cell antibodies and autoantibodies to glutamic acid decarboxylase-containing Purkinje cells in IDDM. PMID- 1425116 TI - Glycemic index versus glycemic response. Nonsynonymous terms. PMID- 1425118 TI - Isolated fatty change of liver as marker of glucose intolerance. PMID- 1425117 TI - Hazard of glucagon test in diabetic patients. Hypertensive crisis in asymptomatic pheochromocytoma. PMID- 1425119 TI - Screening for prediabetes at diabetes camp. PMID- 1425120 TI - Discussing the role of glucagonlike peptide-I. PMID- 1425121 TI - Lp(a) serum concentrations and metabolic control. PMID- 1425122 TI - Perspectives in the treatment of diabetic retinopathy. PMID- 1425123 TI - Islet amyloid: an enigma of type 2 diabetes. PMID- 1425124 TI - Glutamic acid decarboxylase in insulin-dependent diabetes mellitus. PMID- 1425125 TI - Gut hormones and diabetes mellitus. PMID- 1425126 TI - Glucose toxicity in the vascular complications of diabetes: the cellular perspective. PMID- 1425127 TI - Central retinal vein occlusion in young people. AB - In a study performed on 20 subjects with central retinal vein occlusion (CRVO) aged 40 years or less we found the ischemic form in 20%. Disc edema was a common finding at the onset, while macular edema was less frequently seen. Systemic or ocular disorders that could be related with the development of the CRVO were often found; a patient was affected with myasthenia gravis and another with Sturge-Weber syndrome: these two diseases were not previously reported in association with CRVO. In only two of the 11 patients followed-up the visual acuity improved. The visual prognosis in CRVO of young people is often poor; the more frequent cause of the reduced visual acuity is chronic cystoid macular edema. PMID- 1425128 TI - Cyclosporine effects on optic nerve and retinal vasculitis in Behcet's disease. AB - In a prospective, open clinical trial, we studied long-term effects of cyclosporine (CsA) on the optic nerve and retinal vasculitis in 14 Behcet's disease patients. Patients were treated with CsA and corticosteroids for a mean period of 42 months, with a range of 36 to 52 months. They received an initial CsA dosage of 7 mg/kg/day for three days, followed by 5 mg/kg/day, and prednisone 1 mg/kg/day for three to five days, tapered to 0.4 mg/kg/day. CsA was tapered when clinical response was noted. Improvement occurred in visual acuity and visual field defects secondary to papillitis, optic neuritis, macular neuroretinitis, and retinal phlebitis, but not with retinal arteritis. Despite a 12/14 (85%) exacerbation rate, no permanent liver or renal lab tests abnormalities were noted. Intermittent, low-dose CsA therapy may be considered in treatment of acute retinal and optic nerve vasculitis assisted with Behcet's disease. PMID- 1425129 TI - Steady-state accommodation and ocular biometry in late-onset myopia. AB - The steady-state accommodative responses of emmetropes and late-onset myopes was measured for an array of numbers located at -1, -3 and -5 dioptres using an objective infra-red optometer. Responses were compared for passive (reading numbers) and active (adding numbers) conditions. For the passive condition, the late-onset myopes showed a significantly lower accommodative response than the emmetropic group. No significant differences were found between the two groups for the active condition. Ocular biometric characteristics were also measured in emmetropes, late-onset myopes and early-onset myopes using keratometry and ultrasonography. No significant differences in corneal curvature, anterior chamber depth and crystalline lens thickness were found between the groups. Late onset myopes exhibited significantly deeper vitreous chambers than emmetropes, which more than accounted for the difference in refractive error between the two refractive groups. We conclude that, while significant differences exist in the accommodative responses of late-onset myopes and emmetropes, late-onset myopia is due predominantly to elongation of the vitreous chamber. PMID- 1425130 TI - Postcataract against-the-rule astigmatism after phacoemulsification procedure. Characteristic changes over time. AB - To further determine whether postoperative astigmatism is related to the amount of preoperative astigmatism, we analyzed two types of against-the-rule (AR) astigmatism induced by phacoemulsification and aspiration (PEA) procedures. The operations all utilized 10-0 polyester (Mersilene) in double running fashion for the closure of the corneoscleral incisions. The induction and spontaneous regression of several types of astigmatism were analyzed over 6 months. Surgery was all done by one surgeon, with the same surgical procedure and the same number of sutures. In postoperative AR astigmatism less than 0.7 D at 6 months, although the amount of the astigmatism 1 week postoperatively was remarkably increased (2.66 +/- 0.17 D), postoperative astigmatism was decreased 6 months following surgery. On the other hand, in postoperative AR astigmatism greater than 1.5 D at 6 months, the power of the astigmatism 1 week postoperatively (2.12 +/- 0.13 D) was not much higher than the preoperative level (1.38 +/- 0.08 D), but tended to continue increasing even 6 months after surgery. There was no difference in the power of astigmatism between 1 and 3 months postoperatively. The eyes with preoperative astigmatism (e.g. 1.38 +/- 0.08 D) and especially preoperative AR astigmatism (e.g. 1.60 +/- 0.11 D), showed an increase of their astigmatism after the PEA procedure. We discussed some risk factors which may induce greater postoperative AR astigmatism. PMID- 1425131 TI - Postoperative necrotizing sclerokeratitis. AB - The postoperative necrotizing sclerokeratitis is a rare condition occurring shortly after surgical procedures, mainly following cataract extractions. After several exacerbations and remissions spontaneous scleral perforation may occur. In the described case the conservative treatment/topical antibiotics, corticosteroids/failed, therefore the damaged scleral surface was covered with lyophilized dura and the condition came to a standstill. PMID- 1425132 TI - Visual evoked cortical potentials from transient dark and bright stimuli. Selective 'on' and 'off-pathway' testing? AB - The superior hemifields of five normal left eyes were stimulated by novel equal and opposite contrast pattern onset stimuli which were generated on a cathode ray tube. Patterns consisted of 144 discs, each subtending 60 min arc at the viewing distance of 40 cm and were separated by a distance equal to their diameter. Equal and opposite light changes were created by presenting the disc patterns with different luminance values on a uniform constant background (20 cd/m2). Transient visual evoked cortical potentials to the appearance and disappearance of the patterns were recorded separately and analysed. Significant amplitude differences between the responses to bright and dark stimuli were observed with light increment responses being 36-53% larger than the light decrement responses for pattern on-set and 54-80% larger for pattern off-set respectively. This finding is attributed to the difference in the input to the ON and OFF Parallel Pathways which are known to carry light increment and decrement information respectively, as well as differences in the metabolic and discharge rates of these pathways. PMID- 1425133 TI - Effect of morphological abnormalities on blood retinal barrier permeability in diabetic retinopathy. AB - The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (PBRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lens transmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the PBRB by multiple regression analysis. The PBRB was not correlated to morphological abnormalities of non proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p greater than 0.3]. The PBRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (SIRMA) and (2) new vessels (Sneo): PBRB = A+B.SIRMA + C.Sneo with PBRB in nm/sec, A = 1.5 +/- 0.5, B = 0.9 +/- 0.2 and C = 1.7 +/- 0.4, R2 = 0.65, p less than 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities. PMID- 1425134 TI - Some characteristics of saccadic eye movements in children of primary school age. AB - The characteristics of saccadic eye movements have been extensively studied in adults; researches have also been devoted to the saccades of preschool age children. On the contrary, for primary school-age children no data exist; we investigate the eye movements (recorded utilizing an infrared technique) of six children 7 to 11 years old. The main results indicate that the values of some parameters (for example the saccadic latency and duration) are in the same range as the values of the correspondent parameters in adults, while the values of other parameters (in particular peak velocity and mean velocity/peak velocity ratio) are distinctly different from the ones measured in adult subjects. PMID- 1425135 TI - The current management of herpetic eye disease. AB - Herpes simplex disciform keratitis is a difficult condition. The general feeling is that it is an immune disease, mediated by the virus, possibly located in the endothelial cells. It is frequently combined with inflammation in the trabecular meshwork and with uveitis. There is some controversy in relation to treatment and it has been suggested that anti-virals will control herpetic disciform keratitis, particularly if the patient has never had steroids previously. The authors of this paper have, in the past, published data which showed that Acyclovir, with corticosteroid, was necessary in the management of disciform keratitis. The data suggested that Acyclovir on its own was not effective. It remained to be answered whether Acyclovir on its own would be effective in patients who never had steroids for any reason previously. This paper demonstrates clearly that it is necessary, irrespective of whether patients have had steroids in the past or not, to combine corticosteroids with Acyclovir in the management of herpetic disciform keratitis. Acyclovir, on its own, is shown to be ineffective. It has also been suggested that Acyclovir is non-toxic. In a general way this is true, but the authors suggest that Acyclovir ointment does produce a punctate keratitis in patients with tear film disease, and that oral Acyclovir is preferable in such patients. PMID- 1425136 TI - Hyperlipidemia and atherosclerosis in experimental insulinopenic diabetic monkeys. AB - Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non human primate Macaca fuscata. Five diabetic monkeys were kept for 8-19 months and nine for 24-48 months without any insulin treatment. Hyperglycemia (241 +/- 22 mg/dl, M +/- SE less than or equal to 1 year) progressed to 376 +/- 34 mg/dl (greater than 2 years) and ketosis to 3.5 mM (greater than 2 years) during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.4 microU/ml, 2 years). Serum cholesterol increased from 184 +/- 11 (less than or equal to 1 year) to 328 +/- 66 mg/dl (greater than 2 years) with the major increase in LDL-cholesterol (2.7-fold over control, greater than 2 years). HDL cholesterol did not change at all throughout the experimental period. TG increased from 144 +/- 25 (less than or equal to 1 year) to 676 +/- 116 (greater than 2 years) with a major increase in the VLDL fraction (15-fold over control, greater than 2 years). Serum levels of apo B increased to 141 +/- 16 (less than or equal to 2 years) and 223 +/- 8 mg/dl (greater than 2 years) in contrast to control, 73 +/- 2. Morphologically, lipid deposition in the intima and fatty streaks have been observed in the abdominal aorta of all the diabetic monkeys with duration of more than 2 years. In six of the diabetic monkeys atheromatous changes such as intimal and medial thickening with smooth muscle cell proliferation were observed with foam cell formation. Similar atherosclerotic lesions were observed in renal and coronary arteries in at least six of these monkeys. In diabetic monkeys with duration of less than 2 years, mild atherosclerotic lesions were observed in two out of five. The results indicate that long standing insulinopenia leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is a characteristic of lipoprotein disorder. Morphologically, early to moderately advanced lesions of atherosclerosis were observed in aorta, renal and coronary arteries as a result of metabolic derangement due to insulin deficiency. PMID- 1425137 TI - Comparison of subcutaneously administered soluble insulin and des-(B26-B30) insulin-B25-amide in rabbit, pig and healthy man. AB - Subcutaneous injections of soluble human insulin and of the monomeric insulin analogue des-(B26-B30)-insulin-B25-amide were given to fasted rabbits, pigs and healthy man. The time course of blood glucose decline and the rate of appearance of the hormones in the peripheral circulation were studied for doses of 0.35 and 0.7 nmol/kg. In rabbits an identical time course with early glucose nadirs between 45 and 60 min and hormone peaks at about 20 min were observed for both hormones. Similar results were obtained for insulin and the analogue in pigs. When injected into humans, slightly earlier peaks of the analogue at 30 to 45 min were measured compared to insulin peaks at 60 min. In addition, a trend towards faster decline in blood glucose could be demonstrated after analogue injection. In contrast to monomeric insulin analogues produced by recombinant DNA technology, s.c. injections of des-(B26-B30)-insulin-B25-amide do not appear to meet mealtime insulin requirements better than soluble insulin. PMID- 1425138 TI - The dawn phenomenon and diabetes control in treated NIDDM and IDDM patients. AB - The effect of glycaemic control on the early morning plasma glucose rise, 'the dawn phenomenon', was assessed in two matching diabetic patient groups each comprising five NIDDM and two IDDM patients per group, who were otherwise considered to be in poor (HbA1 = 11.2 +/- 0.6%) or good (HbA1 = 7.6 +/- 0.2%) glycaemic control. Hourly plasma concentrations of glucose, insulin, glucagon, cortisol, and growth hormone were measured between 03.00 and 09.00 h. In all the poorly controlled diabetic patients the mean rise in plasma glucose between 06.00 08.00 and 03.00 h was greater than or equal to 1.0 mmol/l. In contrast, the plasma glucose increment was less than 1.0 mmol/l in the well controlled diabetics. The overnight mean insulin levels in the poor and well controlled patient groups were 19.3 +/- 0.5 and 25.0 +/- 0.6 mU/l (P less than 0.001) respectively. Glucagon, cortisol, and growth hormone levels in the early morning showed no significant differences between the two groups. The decline in plasma insulin from 03.00 to 08.00 h and mean cortisol level between 03.00 and 06.00 h were both significantly correlated with the increase in plasma glucose between 03.00 and 08.00 h. We concluded that an increase of 1.0 mmol/l or more in plasma glucose during the early morning is of clinical importance. PMID- 1425139 TI - Profound vasoconstrictive effect of cigarette smoking in diabetics with autonomic neuropathy. AB - Changes in leg skin temperature during and after cigarette smoking were examined in 25 diabetics with autonomic neuropathy (au-neuropathy) (mean age 52 +/- 2 years) and 23 without (mean age 49 +/- 2 years), and 15 normal controls (mean age 49 +/- 2 years) using a Thermoviewer JTG 3300. All subjects were habitual smokers. Japanese Seven Star cigarettes (each containing 1.2 mg nicotine) were used for the test. Tender brand cigarettes (0.3 mg) were used additionally to compare the effect of nicotine content on the results. The smoking-stimulated thermographic pattern in the control group was rather flat, with a slight decrease in temperature followed by a slight increase before returning to the baseline level 15-20 min after smoking. The frequency of the typical temperature decreasing pattern, characterized by a profound decrease and gradual return to the baseline level in about 1 h, was significantly higher in the diabetic group than in the control group (33/48 vs 1/15; P less than 0.005). A comparison of the two diabetic subgroups revealed that the frequency was considerably higher in the subgroup with au-neuropathy (23/25 vs 10/23). These results suggest that au neuropathy affects smoking-induced vasoconstriction in diabetic subjects. The maximum temperature decreases recorded were 1.5 +/- 2.0 and 2.69 +/- 0.24 degrees C in the controls and diabetics with au-neuropathy, respectively. The effect of Tender cigarettes with a low nicotine content was much weaker than that of Seven Star, which further suggests that smoking-induced vasoconstriction was also nicotine-dependent. PMID- 1425140 TI - Retrospective analysis of daily glucose profile in type 1 diabetic patients with continuous subcutaneous insulin infusion (CSII). AB - A retrospective analysis of blood glucose control was performed in 17 type 1 diabetic patients who regularly monitored their blood glucose concentration by visual strips over a period of 3-83 months. Analysis was performed by a patient management software loaded on a personal computer. In this cohort of patients the average daily blood glucose reading was 1.6 +/- 0.3. Blood glucose readings were collected more frequently following meal ingestion (40.3%) than in the post absorptive state (24.6%; P less than 0.05). Blood glucose concentration fluctuated from a basal level of 146 +/- 5 mg/dl to 167 +/- 4 mg/dl in the post prandial phases with an average daily value of 156 +/- 2 mg/dl. Blood glucose values below 80 mg/dl were evenly distributed throughout the day, while hyperglycemia (greater than 300 mg/dl) occurred more commonly after meals (42%). Daily blood glucose was higher during weekends (164 +/- 5 mg/dl) than during weekdays (155 +/- 2 mg/dl; P less than 0.05). A weak correlation was found between the number of blood glucose readings/day and daily blood glucose level. These results suggest that long-term maintenance of satisfactory metabolic control is attainable in type 1 diabetic patients and that this is mainly dependent upon subject self awareness. PMID- 1425141 TI - Is the reuse of needles for insulin injection systems associated with a higher risk of cutaneous complications? AB - Twenty diabetic patients participated in a study to assess if multiple use of needles for insulin injection systems (Pens) is safe under normal daily conditions. The previous mean duration of Pen therapy was 16.3 months. During this time, the 20 patients carried out altogether more than 33,000 injections without any sign of local infection despite needle reuse. Patients were told to use needles if possible for 1, 3, 6, 9, and 12 injections before bacteriological assessment. Bacteriological investigation of these needles showed no contamination, except with one needle used three times, which was colonized with coagulase negative Staphylococcus. In contrast, half of the needles' plastic ground points which touched the skin were contaminated. No signs of infection were observed at the injection sites throughout the study. We conclude that, based on the bacteriostatic effects of commercially formulated insulin and on the siliconisation of needles' surfaces, bacterial growth is sufficiently prevented. Therefore, we can recommend the reuse of pen needles as a simple, safe and cost beneficial procedure. PMID- 1425142 TI - An algorithm for tight glycaemic control in diabetic infarct survivors. AB - An algorithm has been developed to provide predictable control of blood glucose for 48 h following acute myocardial infarction. In 29 diabetic patients intravenous infusion of soluble insulin was started upon admission to hospital and the rate adjusted hourly on the basis of bedside capillary glucose estimations. Insulin infusion rates related to glycaemia were higher in obese patients and those with severe cardiac failure. For all patients mean admission glucose levels were reduced from 18.3 +/- 5.9 mmol l-1 to 9.1 +/- 3.3 mmol l-1 at 4 h and to 8.8 +/- 2.5 mmol l-1 at 6 h. Mean glucose concentrations for 48 h after admission were 8.2 +/- 1.3 mmol l-1 for all patients. Admission glucose levels were slightly higher in patients with severe, compared to those without or mild, cardiac failure (P less than 0.1), but levels over the following 48 h were similar. Doubling insulin infusion rates before meals did not achieve tighter glycaemic control. Hypoglycaemia (glucose less than 3 mmol l-1) occurred on 11 occasions in six patients; only two episodes were symptomatic and only two episodes occurred when the insulin rates were doubled before meals. This algorithm produced tighter glycaemic control than previously published protocols, particularly in patients with severe cardiac failure. Hypoglycaemia is uncommon and the algorithm easy to administer by nursing staff. PMID- 1425143 TI - The relationship between the development and progression of microalbuminuria and arterial blood pressure in type 1 (insulin-dependent) diabetes mellitus. AB - OBJECTIVE: to investigate the association between urinary albumin excretion and arterial blood pressure in type 1 (insulin-dependent) diabetes. RESEARCH DESIGN AND METHODS: urinary albumin excretion and blood pressures were followed prospectively for a mean period of 26 months (range 18-29 months) in 46 young type 1 (insulin-dependent) diabetic subjects without overt nephropathy. Supine blood pressures (BP) were measured by a single observer using a random zero sphygmomanometer. Albumin excretion was assessed at baseline by a timed clinic excretion rate (AER; microalbuminuria = AER greater than 33 micrograms/min), and at follow-up in at least two urine specimens by the albumin/creatinine (A/Cr) ratio (micro-albuminuria = A/Cr greater than 3.7 mg/mmol). RESULTS: 39 subjects initially had normal AERs. Seven had developed microalbuminuria at follow-up: their mean BP rose from 114 +/- 13/62 +/- 13 to 119 +/- 7/77 +/- 5 mmHg (for diastolic BP, P less than 0.05), while there was no change in the mean BP in the remaining 32 patients. A rise in diastolic BP of greater than 10 mmHg occurred in five of the seven subjects who developed microalbuminuria, and in only seven of 32 who did not (P = 0.02). In the seven patients in whom microalbuminuria persisted (n = 3) or progressed to overt proteinuria (n = 4), BP increased from 123 +/- 12/70 +/- 14 to 139 +/- 12/88 +/- 10 mmHg (P less than 0.02 for both). CONCLUSIONS: this study has shown that BP is normal before the onset of microalbuminuria, and that a rise in diastolic BP accompanies the development or progression of microalbuminuria. The rate of rise in BP may be more important than the absolute level in defining 'hypertension' in young diabetic patients with microalbuminuria. PMID- 1425144 TI - Possible participation of a prostaglandin E1 analogue in the aggravation of diabetic nephropathy. AB - A relation between the progression of diabetic nephropathy and glomerular hyperfiltration has been speculated. We describe two cases of non-insulin dependent diabetic males aged 55 and 59 years in whom diabetic nephropathy was aggravated during the administration of limaprost, a a prostaglandin E1 analogue with a vasodilatory action. We also observed a short-term effect of limaprost on renal hemodynamics in three cases with diabetic nephropathy. In case 1, one year after limaprost administration the serum albumin level fell from 3.6 to 2.6 g/dl and the serum creatinine level rose from 1.0 to 1.6 mg/dl. In case 2, 9 months after limaprost administration the serum albumin level fell from 3.6 to 2.9 g/dl and the serum creatinine level rose from 1.8 to 2.3 mg/dl. In the latter stages of limaprost administration, the downslopes of reciprocal serum creatinine against time appeared to be augmented in the two cases. After the 3-day administration of limaprost, the peripheral and renal blood flows, and the glomerular filtration rate (GFR) were observed to rise, but the filtration fraction (FF) and urinary protein output were elevated. Keeping in mind the pre existing renal damage, the increases in GFR and FF suggested acceleration of compensatory glomerular hyperfiltration in less damaged surviving glomeruli. The sustained acceleration of hyperfiltration with long-term administration of limaprost as an exogenous vasodilatory prostaglandin was assumed to eventuate in the aggravation of diabetic nephropathy. Attention should be paid to drugs which increase GFR in patients with established diabetic nephropathy. PMID- 1425145 TI - A comparison of the relationships of the glucose tolerance test and the glycated haemoglobin assay with diabetic vascular disease in the community. The Islington Diabetes Survey. AB - We have compared the relationships of fasting and 2 h blood-glucose during a 75 g oral glucose tolerance test, and those of an affinity chromatography assay of glycated haemoglobin, with the presence of vascular complications of diabetes mellitus in 223 subjects without known diabetes aged over 40 years selected from a community screening study population. The subjects included 15 (6.9%) with newly diagnosed diabetes and 52 (24.1%) with impaired glucose tolerance. Employing receiver operating characteristic analysis, the tests were similar in their relationship with three cases of retinopathy, 19 of microalbuminuria and six of peripheral neuropathy. The prevalence of coronary heart disease, defined as angina, myocardial infarction, or electrocardiographic changes of ischaemia, increased linearly across all four quartiles of both 2 h blood glucose and glycated haemoglobin concentration, but using logistic regression analysis, 2 h blood glucose was a better predictor of coronary heart disease than glycated haemoglobin. Receiver operating characteristic analysis also showed that 2 h blood glucose generally performed better than any of four assays of glycated haemoglobin in classifying those subjects with coronary heart disease. PMID- 1425146 TI - Influence of sympatho-adrenal system on insulin sensitivity using the euglycemic clamp technique. AB - The aim of the present study was to further investigate the role of the adrenergic system on insulin action using the euglycemic clamp technique. Whole body glucose metabolism (GM) was calculated as the glucose infusion rate for maintaining euglycemia under insulin infusion and used as an indicator of insulin sensitivity. Euglycemic clamps were performed in adrenodemedullated, epinephrine treated, phentolamine-treated (alpha-blockade), propranolol-treated (beta blockade), and epinephrine plus phentolamine and/or propranolol-treated rats. The following results were obtained at an insulin level of approximately 80 mU/l. GM in adrenodemedullated rats (13.97 +/- 0.98 mg/kg/min) was significantly higher than that of the control rats (10.26 +/- 0.50 mg/kg/min, P less than 0.01). GM in epinephrine-treated rats (1.7 mg/kg body weight/h) was 2.12 +/- 0.49 mg/kg/min (P less than 0.001 vs. control). Dose-response curves for phentolamine and propranolol established maximally effective doses (3.0 mg and 12 mg/kg body weight/h, respectively). Using these doses, GM in epinephrine plus phentolamine treated rats (4.90 +/- 0.39 mg/kg/min) was significantly higher than that of epinephrine alone and GM in epinephrine and propranolol-treated rats (4.49 +/- 0.47 mg/kg/min) was also significantly higher than that of the epinephrine alone. GM in the epinephrine plus both propranolol and phentolamine (5.94 +/- 0.45 mg/kg/min) was significantly higher than that of the epinephrine alone, but not different from either treatment alone and was not additive. Neither phentolamine alone (9.48 +/- 1.45 mg/kg/min), propranolol alone (10.36 +/- 0.55 mg/kg/min) or the combination of blockades (11.14 +/- 0.65 mg/kg/min) had any effect on GM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425147 TI - An aid for insulin needle destruction for people with failing eyesight. AB - Patients with diabetic retinopathy and failing eyesight have problems in cutting off the needle after insulin injection. We have developed a new aid for attachment to a Becton Dickinson Destruclip needle cutter to simplify needle destruction and make safer handling possible, and studied its effectiveness. The performance time of 10 healthy blindfolded subjects to destroy a needle was compared with and without the aid. The risk of needlestick was also compared. When no aid was used, the time to destroy a needle was on an average: first trial 54 s, second trial 33 s, and third trial 11 s, while with the aid the time was on an average: first trial 16 s, second trial 7 s, and third trial 6 s; thus, the use of the aid shortened the time. Furthermore, without the aid, the frequency of needlestick injury was 1 in 15. With the aid it never occurred. This shows that the new aid for the needle cutter is effective and reduces related injuries. PMID- 1425148 TI - Segmental gut transit in diabetes mellitus: effect of cisapride. AB - Gut transit using radiopaque markers was assessed in 5 healthy subjects and 24 diabetic patients. In the diabetics, various parameters including duration of the disease and diabetic complications, such as neuropathy, retinopathy and nephropathy, were determined, and the relationships between gut transit times and these complications were evaluated. The effect of cisapride on gut transit was studied in 10 diabetic patients. Large intestinal, descending colon, distal colon, and whole gut transit times were delayed in diabetics with autonomic neuropathy compared to controls and to diabetics without autonomic neuropathy (P less than 0.01). There was no difference in proximal colon transit times among them. An inverse correlation was observed between CVRR and the transit times for descending colon, distal colon, large intestine and whole gut. Large intestinal and whole-gut transit times were delayed in diabetics with retinopathy or with nephropathy compared to diabetics without those complications (P less than 0.01). In the diabetics, oral administration of 7.5 mg/day of cisapride for 2 weeks significantly accelerated descending colon transit (P less than 0.05) and partially accelerated distal colon, large intestinal and whole-gut transit. It is concluded that diabetics with autonomic neuropathy have delayed transits for the whole gut and that this finding is apparent to some extent in the distal colon but not in the proximal colon. Chronic oral administration of cisapride, a gastrointestinal prokinetic drug, was effective to improve these gastrointestinal motility disorders in diabetics with autonomic neuropathy. PMID- 1425149 TI - Audit of multiple insulin injection regimens in a large outpatient diabetic population. AB - One hundred out-patients treated by multiple insulin injection regimens underwent clinical audit by retrospective analysis of their case-notes. Patients had been on multiple insulin injection therapy (MIIT) for 1.0-4.5 years (median, 3.6 years) and had had diabetes for 2 months-33 years (median, 8.7 years) at the time of starting pen therapy. Median daily insulin dose per patient did not differ significantly following stabilisation on MIIT or at latest follow-up. The median glycated haemoglobin did not change during each of the 4 years of follow-up. During the year prior to commencing MIIT the patients showed no significant alteration in body weight. Patients' weights rose significantly during each subsequent year. Median weight gains were 0.9 kg (P less than 0.005) during the first year, 1.4 kg (P less than 0.005) during the second year, 0.9 kg (P less than 0.05) during the third year and 1.4 kg (P less than 0.05) during year 4. No such weight gain was recorded in a control group of 30 patients matched for age and duration of diabetes and treated by twice daily insulin injections. Multiple insulin injection regimens used over prolonged periods in a routine clinic setting do not alter metabolic control. However, continuing weight gain appears to occur despite similar daily insulin doses. PMID- 1425150 TI - An immunopotentiator of beta-1,6;1,3 D-glucan prevents diabetes and insulitis in BB rats. AB - The preventive effect of an immunopotentiator, beta-1,6;1,3 D-glucan, on the development of diabetes and insulitis was studied in BB rats. The intravenous administration of 1 mg kg-1 week-1 of beta-1,6;1,3 D-glucan from the age of 4 weeks decreased the cumulative incidence of diabetes from 43.3% (13/30) to 6.7% (2/30) (P less than 0.005) and also the incidence of insulitis from 82.4% (14/17) to 26.3% (5/19) at the age of 20 weeks (P less than 0.002). Eight of nine rats were free from diabetes for 5 weeks after stopping beta-1,6;1,3 D-glucan at the age of 20 weeks. The total numbers of leukocytes in the peripheral blood and spleen of the rats were increased by beta-1,6;1,3 D-glucan treatment (P less than 0.05), whereas their T lymphocytes subsets were not changed. These data indicate that immunopotentiators could modulate the autoimmune mechanisms directed to pancreatic islets and inhibit the development of diabetes in BB rats. PMID- 1425151 TI - Viscosity modulates blood glucose response to nutrient solutions in dogs. AB - The relationship between postprandial blood glucose levels and meal viscosity was studied by adding various combinations of hydroxypropylmethylcellulose to glucose solutions and administering them to female mongrel dogs. Glucose was administered as 5% or 20% solutions in water. Hydroxypropyl-methylcellulose was dissolved in the glucose solutions to yield low (5000 cP measured at 37 degrees C and 1 s-1), medium (15,000 cP) or high (30,000 cP) viscosities. High viscosity hydroxypropylmethylcellulose significantly reduced the maximum blood glucose concentration, Cmax, by 60% (5% glucose meal) and 40% (20% glucose meal) while reducing the area under the blood level vs. time curve (AUC0-3 h) by 40-50%. Medium viscosity hydroxypropylmethylcellulose reduced the Cmax at both glucose levels, but reduced the AUC only for the 5% glucose meal. Low viscosity HPMC lowered the Cmax only after the 5% glucose meal, and had no significant effect on the AUC at either glucose level. The average time to reach maximum concentration, Tmax, was prolonged two- to three-fold at all viscosity levels for the 5% glucose solutions, but was not affected when 20% glucose solutions were administered. It was concluded that hydroxypropylmethylcellulose can effectively retard the absorption of glucose from the gastrointestinal tract, and that the extent of this effect is related to the viscosity of the solution administered. PMID- 1425152 TI - Short- and long-term gliclazide effects on pancreatic islet cell function and hepatic insulin extraction in non-insulin-dependent diabetes mellitus. AB - Nine non-obese males with non-insulin-dependent diabetes mellitus (NIDDM) were evaluated before and after 3 and 12 months (6 patients) treatment with the second generation hypoglycemic sulfonylurea: gliclazide. They underwent an oral glucose tolerance test, intravenous glucose and arginine tests measuring plasma insulin and C-peptide responses. Pre-hepatic insulin production and insulin delivery to peripheral tissues were calculated by deconvolution techniques and hepatic extraction of insulin estimated. An improvement was observed in the beta-cell function of the patients on gliclazide treatment: reduction of fasting plasma glucose associated with a progressive increase in C-peptide level but insulin levels decreased at 12 months, suggesting an increase in hepatic insulin extraction at this time. In the same way, while plasma glucose values after oral and i.v. glucose were greatly reduced at 3 and 12 months treatment, insulin did not change but C-peptide levels increased significantly at 12 month treatment. While the prehepatic insulin secretion rate increased progressively on gliclazide during all glucose challenges, the fractional hepatic insulin extraction fell after 3 and increased at 12 month treatment, with opposite changes in insulin delivered to peripheral tissues. Thus the insulinogenic effect of gliclazide could be masked during long-term administration by a concomitant effect of gliclazide which increases hepatic extraction of insulin. The maintenance of the responsiveness to the non-glucose secretagogue, arginine, as evaluated by the C peptide levels, before and after correction of hyperglycemia, suggested improvement of beta-cell sensitivity to glucose after sulfonylurea treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425153 TI - The association of waist-hip ratio and risk factors for development of IDDM complications in an IDDM adult population. AB - The role of waist-to-hip ratio (WHR) in the metabolic disturbance of IDDM has not been widely explored. Cross-sectional data from the Epidemiology of Diabetes Complications Study were used to examine the associations between WHR and risk factors for IDDM complications such as lipid or lipoprotein levels, blood pressure and fibrinogen. A total of 586 adults (greater than or equal to 18 years of age) were examined. WHR was calculated as the mean of duplicate waist circumference measurements made at mid-point between the iliac crest and the lower costal margin in mid-axillary line divided by the mean of duplicate maximum hip measures. WHR was positively correlated with total cholesterol, LDL cholesterol, triglycerides, systolic and diastolic blood pressure and fibrinogen univariately for both sexes. WHR was negatively correlated with HDL-cholesterol. These correlations remained significant after adjustment for age among females and became less strong, although still significant, for males. The independent effects of WHR to these IDDM risk factors, assessed by multiple linear regression, indicated WHR was related to adverse lipid and lipoprotein levels, but not to fibrinogen or blood pressure. These findings underscore the importance of targeting intervention to IDDM individuals who have a high WHR to reduce known risk factors for IDDM complications especially those for cardiovascular disease, and is consistent with the hypothesis that insulin resistance may have a role to play in IDDM complications. PMID- 1425154 TI - The response of glycated albumin to blood glucose change in the circulation in streptozotocin-diabetic rats--comparison of theoretical values with experimental data. AB - The contribution of the preceding blood glucose level to glycated protein was theoretically analyzed using a linear kinetic model and was compared with experiments using streptozotocin-diabetic rats. We assumed that the glycation process can be described by one irreversible step and that the fraction of glycated protein is small. A formula based on these two assumptions showed that the level of glycated protein was proportional to the weighted mean blood glucose concentration in the preceding period and that the weight function was determined by the metabolic characteristics of each protein. For assessing the usefulness of the present formula, the value calculated for the response of glycated albumin (GA) to acute blood glucose change in streptozotocin-diabetic rats was compared with the data obtained under three experimental conditions. The calculated responses of GA showed a little more retardation than the observed data, but showed enough agreement with them. PMID- 1425155 TI - Teratogenic effects of tolbutamide on early-somite mouse embryos in vitro. AB - The present study investigated the teratogenicity of the oral hypoglycemic agent, tolbutamide, using an in vitro approach, and evaluated the role of its main metabolic effect, hypoglycemia. Teratogenesis was evaluated by culturing early somite mouse embryos for 24 h in serum from rats treated with tolbutamide (79-117 micrograms/ml) or normal rat serum supplemented with tolbutamide (110-152 micrograms/ml). Tolbutamide-treated serum was then supplemented with glucose to control for potential effects of hypoglycemia. Mouse embryos demonstrated high malformation rates following exposure to serum from tolbutamide-treated rats (79%) or normal rat serum supplemented with tolbutamide (85%) compared with controls (4%), and defects included cardiac, ocular, neural tube, and somite abnormalities. Overall growth was reduced in treated embryos and yolk sacs, as determined by total protein contents. Embryonic growth and malformation rates were not improved by glucose supplementation of hypoglycemic tolbutamide-treated serum. Thus, tolbutamide produces malformation in mouse embryos in vitro at concentrations comparable to those in human serum, and the effects do not appear to be mediated by hypoglycemia. The potential risk of tolbutamide on the developing embryo must be considered in the therapy of pregnant diabetic patients. PMID- 1425156 TI - The effects of superphysiologic hyperinsulinemia on glucose and lipid metabolism in glucose-tolerant offspring of patients with non-insulin-dependent diabetes mellitus (NIDDM). AB - First-degree relatives of patients with NIDDM manifest severe insulin resistance despite normal glucose tolerance test. To examine the mechanisms underlying the normal glucose tolerance, we evaluated the serum glucose/C-peptide/insulin dynamics and free fatty acid (FFA) as well as substrate oxidation rates and energy expenditure (EE) (indirect calorimetry) in nine young offspring of NIDDM patients (mean +/- SEM age 30 +/- 2.3 years, body mass index 24.2 +/- 1.2 kg/m2). Nine age-, sex- and weight-matched, normal subjects with no family history of diabetes served as the controls. Metabolic parameters were measured before, during and after a two-step glucose infusion (2 and 4 mg/kg.min) for 120 min. Mean basal serum glucose, insulin and C-peptide levels were similar in both groups. During 2 mg/kg.min glucose infusion, mean serum insulin and C-peptide rose to significantly (P less than 0.05-0.02) greater levels in the offspring vs. controls, while serum glucose levels were similar. With the 4 mg/kg.min glucose infusion, mean serum glucose, insulin and C-peptide levels were significantly (P less than 0.02-0.001) greater in the offspring at 100-120 min. Isotopically derived (D[3-3H]glucose), basal hepatic glucose output (HGO) was not significantly different between the offspring vs. controls (1.86 +/- 0.30 vs. 1.78 +/- 0.06 mg/kg.min). During glucose infusion, basal HGO was partially suppressed by 66% at 60 min and by 100% at 120 min in the offspring. In contrast, HGO was completely (100%) suppressed at both times in the controls. Following cessation of glucose infusion, HGO rose to 1.64 +/- 0.12 mg/kg.min in the offspring and 1.46 +/- 0.05 mg/kg.min in the controls (P less than 0.05) between 200 and 240 min. These were 88% and 82% of the respective basal HGO values. At low glucose infusion (t = 0-60 min), the mean absolute, non-oxidative glucose disposal remained 1.5-fold greater in the offspring while at higher glucose infusion, nonoxidative glucose metabolism was not different in both groups. Throughout the study period, oxidative glucose disposal rate was not significantly different in both groups. The mean basal FFA was significantly greater in the offspring vs. controls (865 +/- 57 vs. 642 +/- 45 microEq/l). It was appropriately suppressed during glucose infusion to a similar nadir in both groups (395 +/- 24 vs. 375 +/- 33 microEq/l). The mean basal lipid oxidation was also significantly greater in the offspring than controls (1.06 +/- 0.05 vs. 0.75 +/- 0.04 mg/kg.min, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1425157 TI - Antireticulin antibodies in sera of children with insulin-dependent diabetes mellitus. AB - Sera from 125 children (mean age 9.5 +/- 3.9; range 0.5-18 years) with newly diagnosed insulin-dependent diabetes mellitus were examined for the presence of antireticulin antibodies (ARA). Fifty-four of these children were followed up over a period of 150-400 days after the onset of the disease with respect to their serum ARA. The indirect immunofluorescence method on human and rat tissue was used to detect autoantibodies. In each serum, the level of islet cell antibodies (ICA) was determined. The prevalence of ARA in our diabetic children (16%) was significantly higher than in normal population (P less than 0.05). In sera of newly diagnosed ICA-negative children, ARA were more frequent than in ICA positive patients (P less than 0.025). The difference in ARA prevalence was even higher when patients were divided into two groups one with less and one with more than 30 JDFu (P less than 0.005). On the contrary, sera sampled 150-400 days after the manifestation of IDDM revealed neither a positive nor a negative association between ICA and ARA. Thus, the negative association of ARA with ICA in the early stages of IDDM may suggest the role of an autoimmune response to reticulin in part of the IDDM patients, and gives further evidence to the heterogeneity of IDDM. PMID- 1425158 TI - Comparative effects of captopril versus nifedipine on proteinuria and renal function of type 2 diabetic patients. AB - Our study compared the effects of an angiotensin-converting enzyme inhibitor (captopril) versus a calcium antagonist (nifedipine) on proteinuria and renal function in patients with diabetic nephropathy. A randomized follow-up study was designed. Type 2 diabetic patients, with established diabetic nephropathy (proteinuria greater than 0.5 g/24 h), were treated with nifedipine (10 patients, group A) or captopril (10 patients, group B) for 6 months. Arterial blood pressure, metabolic parameters, proteinuria and renal function were measured and compared. Mean percentage differences for glomerular filtration rate, renal plasma flow and filtration fraction between the two groups were calculated. No significant differences were observed in serum glucose, glycosylated hemoglobin (hemoglobin A1c), Na+, K+ or albumin in either group or between groups. Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months (Mann-Whitney U test, P = 0.03). Proteinuria was similar in both groups at randomization, but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril (P less than 0.01). A significant decrease in filtration fraction was observed in group B with an increase in group A (Mann Whitney U-test, P = 0.03). Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria. It is concluded that antihypertensive treatment with captopril, but not with nifedipine, reduced proteinuria in patients with diabetic nephropathy, although a better mean blood pressure was obtained with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425159 TI - The value of glycosylated haemoglobin as a substitute for the oral glucose tolerance test in the detection of impaired glucose tolerance (IGT). AB - In a prospective study of South African Indian subjects with IGT, glycosylated hemoglobin [specifically HbA1 (HbA1(a+b+c)] and its relationship to the oral glucose tolerance test (OGTT) was studied in 128 study subjects who were classified IGT a year previously (Year 0 of study) and in 64 control subjects. At Year 1 of the study, the standard 75-g OGTT was performed on all subjects; study subjects were further divided into three groups based on World Health Organisation criteria [Normal (N), impaired glucose tolerance (IGT), diabetes mellitus (D)]. HbA1, a glycosylated hemoglobin (GHb), was measured by a cation exchange microchromatographic method. Based on OGTT results, 47 of the 128 study subjects were classified IGT, 41 diabetes (newly-diagnosed diabetes) and 40 subjects had normal glucose tolerance. Mean GHb was significantly higher in the D group (7.61 +/- 1.76%) compared to the control group (6.99 +/- 1.22%) and the N group (6.9 +/- 1.12%), respectively (P less than 0.05); there was no significant difference between the IGT group (7.48 +/- 1.44%) and each of the other three groups. Compared to the OGTT, GHb was relatively insensitive in the diagnosis of IGT or diabetes mellitus: only 17% of the IGT group and 26.8% of the D group has elevated GHb values; the specificity of GHb as a measure of normal glucose tolerance was 85.9%. The majority of subjects, irrespective of the category of glucose tolerance, had GHb levels within the normal range and there was marked overlap between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425160 TI - Effect of insulin on serum amino-terminal propeptide of type III procollagen in non-insulin-dependent diabetes mellitus. AB - The effect of insulin on the serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) was investigated in patients with non-insulin dependent diabetes mellitus, whose disease was unsatisfactorily controlled by oral drugs. Before insulin therapy the PIIINP values of the patients (3.2 +/- 1.3 micrograms/l, n = 38) varied within the range of healthy subjects (3.1 +/- 0.6 micrograms/l, n = 50, NS). Insulin therapy (6-20 IU at bedtime plus the oral drugs) improved the glycemic control and increased the serum PIIINP during a 4 week (3.1 +/- 0.9 to 3.8 +/- 1.1 micrograms/l, P less than 0.01, n = 8) and an 8 week period (3.2 +/- 1.3 to 3.8 +/- 1.6 micrograms/l, P less than 0.001, n = 22). The values were still elevated after 6 months on insulin (3.5 +/- 1.5 to 4.0 +/- 1.7 micrograms/l, P less than 0.01, n = 12). Placebo-insulin did not alter the concentration of PIIINP (3.1 +/- 0.6 to 2.8 +/- 0.6 micrograms/l, NS, n = 8) whereas the glycemic control improved and body weight decreased. The PIIINP values correlated with fasting insulin before (r = 0.403, P less than 0.05, n = 30) and after the therapy (r = 0.452, P less than 0.001, n = 60). Insulin therapy, while correcting the hormone deficiency and restoring glucose and protein metabolism, seems to activate the synthesis of type III procollagen in patients with NIDDM. This may promote the atherosclerotic process. PMID- 1425161 TI - Identification of early metabolic defects in diabetes-prone Australian aborigines. AB - The aim of the present study was to identify in young, diabetes-prone subjects the early abnormalities which may predispose to the development of type 2 diabetes. We studied 10 full-blood Australian Aborigines all of whom had a family history of diabetes and who were from an urbanised community with a high prevalence of this disorder. They were compared to 10 age- and body-mass-index matched Caucasian controls with no family history of diabetes. Glucose kinetics were measured basally and following an oral glucose load. Fasting plasma glucose was equal in the two groups, but 2 h following the 75 g glucose load, the Aboriginal subjects had higher glycaemia than the controls (P less than 0.01). Insulinaemia was higher in the Aborigines both basally and following the glucose drink (P less than 0.05). Despite the hyperinsulinaemia, hepatic glucose production was higher in the Aboriginal subjects (P less than 0.01), while metabolic clearance rate was lower. It is concluded that in young Australian Aborigines with a strong family history of type 2 diabetes, both hepatic and peripheral insulin resistance are early abnormalities. PMID- 1425162 TI - Prevalence of childhood diabetes in an urban population in south India. AB - The objective of the study was to estimate the prevalence of insulin-dependent diabetes in children less than or equal to 15 years in an urban area in south India, by a population study. Three zones from the northeastern part of the city demarcated by the Directorate of Census were chosen. Ascertainment of the cases from these zones was made (a) by collecting data from the major hospitals and diabetes clinics by personal visit; (b) by questionnaire sent to medical practitioners in the area; and (c) from the chemists and druggists who sell insulin. Recommendations of the Diabetes Epidemiology Research International Registry Group were used. Thirty children with insulin-dependent diabetes with age at diagnosis less than or equal to 15 years were identified. The prevalence was 0.26/1000. The peak age at diagnosis was 12 years. This first population based study of prevalence of insulin-dependent diabetes in south India shows that insulin-dependent diabetes is not rare. It is higher than reported from many other Asian countries. PMID- 1425163 TI - [Biological activity of N,N'-bis(3-triethoxysilylpropyl)thiocarbamide]. PMID- 1425164 TI - [Hypnosis in Macaca rhesus]. PMID- 1425165 TI - [Priming of resident macrophages with immunopeptides]. PMID- 1425166 TI - [Mechanism of the bacteriocidal action of iodine and its compounds]. PMID- 1425167 TI - [Effect of taurine on the ultrastructure of synapses from parallel fibers to Purkinje cells in the frog cerebellum]. PMID- 1425168 TI - [Identification of DNA-binding proteins of the intracellular virion of the vaccinia virus]. PMID- 1425169 TI - [Frequency resolution of dolphin hearing]. PMID- 1425170 TI - [Fractal structure of microorganism colonies]. PMID- 1425171 TI - [Formation of pH-waves caused by expansion of a bacterial population in agar culture media]. PMID- 1425172 TI - [Interaction between hair surface and bacteria during a change in the mammalian physical state]. PMID- 1425173 TI - [Various features of the bacteriocidal mechanism of heavy metals]. PMID- 1425174 TI - [Selectivity of squirrel striatal cortex neurons (frontal and peripheral field of vision) on the rate of movement of visual stimuli]. PMID- 1425175 TI - [Microsymbionts of the Galliformes digestive tract]. PMID- 1425176 TI - [Effect of cytochalasin D, diphtheria toxin, and ricin on the localization of eukaryotic elongation factor 2 along actin filament bundles in fibroblasts]. PMID- 1425177 TI - [The process of RNA secondary structure folding. Computer modeling at genes 219 and 1146 of tRNA]. PMID- 1425178 TI - [Model of the spatial structure of the C-terminal fragment Thr-Thr-Asn-Tyr-Thr of peptide T, inhibiting the reproduction of the human immunodeficiency virus]. PMID- 1425179 TI - [Study of the tissue specific Ca2+-dependent regulation of mitochondrial processes with thermostable comuton from rat liver]. PMID- 1425180 TI - [Localization of elongation factor 2 in murine embryonal fibroblasts by immunoelectron microscopic data]. PMID- 1425181 TI - [Ultrastructure of dermal melanophores of Xenopus laevis larvae in mitosis]. PMID- 1425182 TI - [Functional morphogenesis in organ cultures of the middle abdominal specific skin gland of the Djungarian hamster (Phodopus campbelli, Rodentia, Mammalia)]. PMID- 1425183 TI - [Detection of extended parallel complementary sequences in genomes of various organisms]. PMID- 1425184 TI - [The role of structural elements of the 5'-untranslated sequence of potato X virus RNA (alpha-beta-leader) in determining its activity as a translational enhancer]. PMID- 1425185 TI - [The effect of ecdysterone on carbachol contracture of ureteral smooth muscle and Mg2+,ATP-dependent transport of Ca2+ through the sarcolemma]. PMID- 1425186 TI - [Synthesis of biologically active recombinant human interleukin-1alpha in Escherichia coli cells]. PMID- 1425187 TI - [Group of acid soluble brain proteins including two forms of GAP43 neuronal proteins]. PMID- 1425188 TI - [Possibility of compensating for programmed regulation of fine movements after damage to the ventrolateral nucleus of the thalamus]. PMID- 1425189 TI - [Analysis of spontaneous and diazepam-induced differences in the EEG and conflict behavior of C57Bl/6 and BALB/c mice]. PMID- 1425190 TI - [Social conflict and tumor growth]. PMID- 1425191 TI - [Preparation of a highly purified recombinant conjugate of beta-galactosidase beta-interferon for immunoenzyme analysis]. PMID- 1425193 TI - [Duodenase--a new serine proteinase with unusual specificity]. PMID- 1425192 TI - [Aberrant phenotypes of the Ldh-B locus in hybrid populations of the Rana esculenta complex (Amphibia, Ranidae)]. PMID- 1425195 TI - [Evolutionary logic of functional brain asymmetry]. PMID- 1425194 TI - [Various behavior features of adult prenatally irradiated rats]. PMID- 1425196 TI - [Comparative study of flavin adenine dinucleotide binding of glycogen phosphorylase b with protein-glycogen particles]. PMID- 1425197 TI - [Interaction of Oct-binding transcription factors with a large series of "noncanonical" oct-sequences. Primary sequence of murine Oct-2B cDNA]. PMID- 1425198 TI - [Specific aminoacylation of oligo U-CCA lysyl-tRNA-synthetase molecules]. PMID- 1425199 TI - [Delayed conformational changes of muscle glycogen phosphorylase b, caused by recording the rate of digestion of the enzyme by trypsin]. PMID- 1425200 TI - [Double system of super instability in Drosophila melanogaster as a model for studying genetic recombination processes]. PMID- 1425201 TI - [Photochemical modification of nitrogen bases and spatial organization of lyotropic DNA liquid crystals]. PMID- 1425202 TI - [Physico-chemical and catalytic properties of recombinant horseradish peroxidase, synthesized in Escherichia coli]. PMID- 1425203 TI - [Induction of the posture asymmetry factor activity in the spinal cord of spinal rats caused by unilateral electrical stimulation of the hind extremities]. PMID- 1425204 TI - [Extracellular mechanism of the anti-tumor manifestation of LAK-supernatants]. PMID- 1425205 TI - The influence of seaprose on erythromycin penetration into bronchial mucus in bronchopulmonary infections. AB - In bronchopulmonary infections antibiotics can be combined with other drugs, called mucoactive drugs, that act to reduce the abnormal viscoelasticity of the mucus enabling a deeper penetration of more antibiotic into the mucus. Seaprose is a protease that interacts with the polymeric fibrillar structure of the bronchial mucus to shorten the long chains of mucoproteins, DNA and other macromolecules, thus reducing the viscosity of the mucus. In order to assess whether the combination of seaprose (60 mg/8 h) plus erythromycin (500 mg/8 h) allows higher antibiotic levels in sputum than erythromycin (500 mg/8 h) plus placebo, the pharmacokinetic behaviour in sputum and in blood of these two treatments was investigated in a double-blind study in two groups of twenty patients each with bronchopulmonary infections. Serum and sputum levels were determined for each patient at the first and seventh day of the two drug regimens. Statistically significant differences for peak, AUC and MRT, were observed for erythromycin between the first and last dose in the group of patients treated with seaprose plus erythromycin; moreover significant differences for these parameters were observed between the two groups. These findings indicate the presence of a pharmacokinetic synergism between seaprose and erythromycin which allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages. PMID- 1425206 TI - Protective effect of levodropropizine against cough induced by inhalation of nebulized distilled water in patients with obstructive lung disease. AB - Levodropropizine is a recently developed, peripherally active antitussive agent which is widely used in clinical practice. In order to obtain further information on the spectrum of activity of this compound in experimental clinical models, a double-blind controlled study was carried out to evaluate the potential effect of the drug against cough and bronchoconstriction induced by inhalation of an ultrasonically nebulized solution of distilled water in patients with obstructive lung disease. Twenty patients were randomly divided into two groups, which received levodropropizine (60 mg t.i.d.) or placebo respectively for 7 consecutive days. Parameters evaluated at baseline and on the last day of treatment included (i) results of respiratory function tests (FEV1, IVC, FVC, TIFF, PEF, MEF75, MEF50, MEF25) performed before the stimulation test with nebulized water; (ii) total number of coughs during a 2-hour period after the stimulation test; (iii) bronchial responsiveness, quantified by calculating the volume of nebulized water required to induce a 20% reduction of FEV1 below the basal level. At pretreatment, the tussive response was very similar in the two groups. A significant decrease in number of coughs (from 34.4 +/- 8.4 at baseline to 15.6 +/- 4.9 post-treatment, p less than 0.01) was observed after administration of levodropropizine, whereas placebo treatment produced no significant effect (number of coughs: 29.6 +/- 4.9 at baseline vs 24.8 +/- 9.6 post-treatment, N.S.). Bronchial responsiveness decreased significantly (compared to baseline) in both treatment groups, without any significant difference between drug and placebo. Respiratory function tests were not significantly affected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425207 TI - Effects of macrolides on ultrastructure of Staphylococcus aureus during postantibiotic phase. AB - The postantibiotic effects (PAEs) of macrolide antibiotics, such as midecamycin acetate (Miocamycin, MOM), erythromycin (EM), josamycin (JM) and clarithromycin (CAM), on Staphylococcus aureus and the ultrastructure of the pathogen during the postantibiotic phase were investigated. After exposure to 2 x MIC for 2 h, MOM showed the longest PAE of 3.9 h, while EM, JM and CAM showed PAE durations 1.2, 2.5 and 1.9 h, respectively. On examining the serum levels of these agents in man, the longest PAE of 2.4 h was induced by exposure to MOM. JM and CAM induced PAEs for durations of 1.4 and 1.3 h, but EM hardly induced the PAE. The ultrastructure was examined by transmission electron microscopy, and thick cell walls with an undulating outer layer and a multiple thick cross-section were observed for 4 h after exposure to 2 x MIC of MOM for 2 h. After exposure to 2 x MIC of EM, JM and CAM for 2 h, ultrastructural changes were observed for 1, 2 and 2 h, respectively. The size of these cells was about 1.5 to 2 times larger than the normal cells. Ultrastructural changes in S. aureus were observed during the PAE phase of each macrolide. PMID- 1425208 TI - Efficacy of tosufloxacin in the treatment of experimentally induced intra abdominal infections in rats. AB - A reproducible experimental model of intra-abdominal infections in rats has been devised in order to simulate intra-abdominal sepsis in patients. Preoperatively, the rats were fed with lean ground beef for two weeks in order to change the intestinal flora to one similar to that of humans. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was reestablished by an end-to-end anastomosis. The segment of ileum was then returned to the abdominal cavity. This experimental model was used to compare the efficacy of tosufloxacin alone and in combination with metronidazole, with the combination gentamicin and metronidazole in the treatment of intra-abdominal infections. Eighty per cent of the untreated animals died within three days. Within three days 20% of the animals receiving tosufloxacin died. Animals treated with tosufloxacin plus metronidazole or gentamicin plus metronidazole had a significantly decreased mortality and increased cure rates during the experimental period. Only 5% of these animals died. Thus the combination of tosufloxacin and metronidazole seems to be as successful as gentamicin plus metronidazole in the treatment of intra-abdominal infections. PMID- 1425209 TI - Compared kinetics of 2-(2,3-dihydro-5-acetoxy-4,6,7-trimethylbenzofuranyl) acetic acid (IRFI 016) and its active metabolite 2-(2,3-dihydro-5-hydroxy-4,6,7 trimethylbenzofuranyl) acetic acid (IRFI 005) in plasma and bronchial alveolar liquid in mice. AB - The concentration of 2-(2,3-dihydro-5-acetoxy-4,6,7-trimethylbenzofuranyl) acetic acid (IRFI 016) and its active metabolite 2-(2,3-dihydro-5-hydroxy-4,6,7 trimethylbenzofuranyl) acetic acid (IRFI 005) in bronchial alveolar liquid (BAL) and plasma of mice were studied. IRFI 016 and its active metabolite IRFI 005 are both present in BAL and plasma after oral administration of IRFI 016. In BAL no delay times were noted, in comparison with plasma, regarding Cmax time nor significant variation of t1/2 and the elimination constant (Kel). IRFI 016, orally administered, is very rapidly absorbed and, both in unaltered form and as its active metabolite, reaches the anatomic site where it carries out its principal pharmacological activity, according to the same kinetic course observed in plasma. PMID- 1425210 TI - Tetracycline inhibition identifies the cellular sources of collagenase in gingival crevicular fluid in different forms of periodontal diseases. AB - Tetracyclines have recently been shown to inhibit the activity of mammalian matrix metalloproteinases, i.e. type I collagenase (MMP-1) and type IV collagenase/gelatinase (MMP-2). The specificity of this effect, however, has not been examined in detail. In the present study, doxycycline (a clinically widely used commercial tetracycline) and 4-de-dimethylaminotetracycline (CMT-1, a chemically modified non-antimicrobial tetracycline) were tested, at a wide range of concentrations, for their ability to inhibit human neutrophil and fibroblast interstitial collagenases, which are distinct gene products, as well as collagenase in human gingival crevicular fluid (an inflammatory exudate in periodontal lesions) obtained from adult, juvenile and diabetic adult periodontitis patients. The concentrations of these two tetracyclines, required to inhibit 50% of the collagenase activity (IC50), were found to be 15-30 microM for purified human neutrophil collagenase as well as collagenase in gingival crevicular fluid of adult periodontitis patients and diabetic adult periodontitis patients, thus approximating in vivo therapeutic tetracycline levels. In contrast, the fibroblast collagenase and collagenase in gingival crevicular fluid of patients with juvenile periodontitis were relatively resistant to tetracycline inhibition: the IC50 for doxycycline and CMT-1 were 280 and 500 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425211 TI - First effects of warning labels on alcoholic beverage containers. AB - Health warning labels are now required on alcoholic beverage containers in the United States. This study addresses who has seen these labels and respondents' reported changes in relevant knowledge, attitudes and behavior. Random samples of adults in the general population of the United States were interviewed by telephone 6 months prior to and 6 months after the enactment in November 1989 of the warning label law (N = 2006 and 2000, respectively). Six months after introduction of warning labels, over one fifth of the respondents reported having seen the labels. Greater proportions of key target groups, such as heavy drinkers and young men at risk for drunk driving, reported seeing the warnings. No statistically significant changes in knowledge of the health risks included on the labels were detected, but we found that knowledge levels for two non-included potential warnings had declined somewhat. After controlling for demographics and alcohol consumption, respondents who probably saw the warning labels were significantly more likely to report several behaviors indicative of heightened awareness of, and caution regarding, the hazard of drinking and driving and of drinking during pregnancy, hazards that are both included on the warning labels. PMID- 1425212 TI - Alcohol consumption and rates of personal violence in Australia. AB - A time-series analysis of suicide and homicide rates in Australia from 1966 to 1985 revealed that suicide rates were lower and homicide rates higher in years when more alcohol was consumed per capita. The association of alcohol consumption with homicide was expected, but the association with suicide was opposite to that predicted. PMID- 1425213 TI - Attitude towards alcohol, church attendance and denominational identity. AB - This paper describes the development of a 16-item Likert scale of attitude towards alcohol. Data derived from 315 individuals, concerned with various forms of youth work in England, demonstrate that both denominational affiliation and frequency of church attendance are significant determinants of attitudes towards alcohol. Membership of the Free Churches and frequent church attendance are associated with less liberal attitudes. These conclusions are discussed against the background of previous discrepant findings relating religiosity with alcohol use and abuse and contemporary sociological theories regarding the compartmentalisation of religious beliefs. PMID- 1425214 TI - Unidimensionality of alcohol dependence syndrome? AB - To evaluate the coherence of Alcohol Dependence Syndrome (ADS), as per DSM-III-R criteria, 72 and 223 subjects with alcohol dependence disorder from Hospital and Community settings, respectively, were interviewed. Nine DSM-III-R criteria assessing the dependence syndrome were factor-analysed. A single factor model provides an adequate description of the interrelationship among the nine criteria and supports the coherence of the dependence syndrome for the hospital sample but not for the community. A two factor model, namely 'withdrawal' and 'social', fits the community data. When the criteria were combined into cumulative scales, they formed good approximations of unidimensional Guttman scales for both the hospital and community settings. For hospital data, preoccupation was the highly central criterion (lambda = 0.95) in defining the dependence syndrome while 'can't stop' (v = 0.11) measured the most severe level of dependence. In the community the 'socially dysfunctional use' identified as a separate secondary factor measured the most severe level of dependence. PMID- 1425216 TI - Psychiatric symptoms in drug abusing adolescents. AB - Psychiatric symptoms and psychosocial variables were investigated in 46 adolescent drug abusers referred to a psychiatric clinic. There were high rates of behavioural symptoms (mostly oppositional and delinquent), emotional symptoms (mostly depressive) and an abundance of adverse life events and family dynamics. When compared to a control group of non-abusing adolescents, drug users were only more behaviourally disturbed. Cluster analysis of the drug abusing adolescents showed that they fell into three distinct groups of (1) behavioural dysfunction (76%); (2) family dysfunction (16%); and (3) emotional dysfunction (8). The clinical implications of these findings are discussed. PMID- 1425215 TI - Effects of ethanol and toluene on fixed-ratio performance in short sleep and long sleep mice. AB - This study examined the effects of ethanol (EtOH) and toluene on fixed-ratio (FR) responding in mice selectively bred for sensitivity to the effects of EtOH on sleep time. Although the more sensitive long sleep (LS) mice showed greater EtOH induced impairment in a motor performance task than did the less sensitive short sleep (SS) mice, changes in FR performance in the two lines did not differ in response to EtOH, regardless of route (oral or intraperitoneal) or time (40 vs. 60 min pre-session) of administration. These results emphasize the importance of considering task variables in determination of the behavior of different genotypes. In contrast to results with EtOH, the volatile inhalant toluene produced different effects on FR responding in the selected lines, with SS mice being more sensitive than LS mice. PMID- 1425217 TI - Adolescent drug use, health and personality. AB - Four factors have confounded the association between drug use and morbidity: (a) known drug users may be less healthy than unknown drug users; (b) drug users are rarely compared to control subjects; (c) the socio-economic status of drug users predisposes them to ill-health; (d) the personality of drug users predisposes them to ill-health. Here, controlling for these confounds, in a study of 210 adolescent drug users it was found that subjective ill-health was more strongly related to drug use than was objective ill-health. Drug use was related to neuroticism and psychopathic deviance. Controlling for personality, drug use accounted for little additional variance in health. It is concluded that drug use and health are not strongly related amongst adolescent drug users, although, because of their personalities, drug users tend not to feel well. Implications are discussed for the self-treatment explanation of drug use and for the design of preventative programmes. PMID- 1425218 TI - Cyclical breast pain--what works and what doesn't. PMID- 1425219 TI - Pen injectors for insulin. PMID- 1425220 TI - How to anticoagulate. PMID- 1425222 TI - Laying foundations for sound health care. PMID- 1425221 TI - Nimodipine for delayed cerebral ischaemia after subarachnoid haemorrhage. PMID- 1425223 TI - [Activating care. Theory and practice in community nursing]. PMID- 1425224 TI - [Does the patient always always have to take center stage?]. PMID- 1425225 TI - [Nursing opinion. Presented by the work group "Ambulatory Care" of the Baden Wurttemberg federation of the German Professional Association for the nursing professions]. PMID- 1425226 TI - [Continuing education towards nursing administration for deaconess' social work. Situation and perspectives]. PMID- 1425227 TI - [Modified rules for working time in the social work office. Flexibility of working time as an instrument for the attraction of qualified nursing personnel]. PMID- 1425228 TI - [Transformation of working time flexibility in a hospital ward]. PMID- 1425229 TI - [Improvement of care for the elderly, sick and those needing care. Report on the results of the model trial of the Baden-Wurttemberg province from the viewpoint of the participating city of Ostfildern]. PMID- 1425230 TI - [Home short-term care]. PMID- 1425231 TI - [Care of severely ill tumor patients during the border time between hospital care and ambulatory care]. PMID- 1425232 TI - [Organization of pediatric nursing at home in Stuttgard]. PMID- 1425233 TI - [Primary care in home nursing]. PMID- 1425234 TI - [The new nursing contract for the wards of the Deaconess' work in Wurttemberg]. PMID- 1425235 TI - [Nursing--a profession with open borders]. PMID- 1425237 TI - [Learning to lead without suffering. A Bavarian pilot project]. PMID- 1425236 TI - [The septic patient]. PMID- 1425238 TI - [Requirements on the qualification of teachers in the nursing professions--from the viewpoint of the program "Health for all in the year 2000"]. PMID- 1425239 TI - [Requirements for the qualification of teachers in the nursing professions--with a view on the European domestic market after 1992]. PMID- 1425240 TI - [Position of the federal committee]. PMID- 1425241 TI - [Qualification of teachers in nursing schools. The situation in Germany. 1. Models, problems and perspectives in the training of nursing teachers]. PMID- 1425242 TI - [2. Course of studies in medicapedagogy and nursing pedagogy in Berlin]. PMID- 1425244 TI - [Course of studies in medical pedagogy and nursing pedagogy. The situation in Switzerland]. PMID- 1425245 TI - [20 years of federal commission 1972-1992--development and perspectives]. PMID- 1425243 TI - [Course of studies in medical pedagogy and nursing pedagogy. The situation in Austria]. PMID- 1425246 TI - [Need for security of the nursing personnel from the view point of nursing administration]. PMID- 1425247 TI - [The carriers of legislated accident insurance as partners of health services in labor protection and accident prevention]. PMID- 1425248 TI - [The security aide. Tasks and possibilities in workers' protection]. PMID- 1425249 TI - [Work safety. Danger potential for personnel on ward duty]. PMID- 1425250 TI - [Stab wounds from canulas--a crucial accident in the hospital]. PMID- 1425251 TI - [Prevention of back injuries in nurses]. PMID- 1425252 TI - [Medical equipment regulation]. PMID- 1425253 TI - [Cancer--a disease that changes family life]. PMID- 1425254 TI - [Pastoral care of families with children who have cancer]. PMID- 1425255 TI - [Care of children with cancer]. PMID- 1425256 TI - [The Tubingen sibling house]. PMID- 1425257 TI - [The current status of nursing science]. PMID- 1425258 TI - [Nursing examination--the practical part]. PMID- 1425259 TI - [Structures for the qualification in the nursing professions]. PMID- 1425260 TI - [Physical exercise tolerance in chronic obstructive emphysematous bronchitis and coronary heart disease under antiobstructive therapy]. AB - 19 consecutive patients (18 men, one woman, mean age 61.4 [49-73]years) with chronic obstructive airways disease (bronchitis and emphysema) together with angiographically confirmed coronary heart disease were studied to investigate their cardiopulmonary exercise tolerance and the effects of bronchodilators on their myocardial ischaemia. Because they were receiving drug therapy for angina or because they had previously undergone aortocoronary bypass operation or balloon dilatation, the patients were symptom-free. In three cases slight ischaemia was demonstrable during maximal exertion. Aerobic and anaerobic exercise capacity was determined by spiroergometry after inhalation of salbutamol (S, 0.2 mg) alone or in combination with oxitropium bromide (O, 0.2 mg). The supplementary effect of oral theophylline (T, 15 mg/kg.day) was studied in 13 patients. In terms of maximal aerobic exercise tolerance the following improvements were noted: energy output (watts): S: + 6.3%; S and O: + 12.3% (P < 0.05); S, O and T: + 14.0% (P < 0.01). Oxygen uptake (ml/min): S: + 8.2% (P < 0.05); S and O: + 18.2% (P < 0.01); S, O and T: + 35.4% (P < 0.01). Maximum exercise capacity was not significantly improved, although maximum oxygen uptake was significantly increased by the two-drug combination by 16.9% (P < 0.05) and by the three-drug combination by 19.2% (P < 0.05). Maximum minute volume and tidal volume rose significantly, though respiratory rate was unchanged. Heart rate and blood pressure remained practically unaffected by the treatment, both at rest and during exertion. There was no evidence of significant aggravation of ventricular arrhythmias or of ischaemia during ergometric testing. PMID- 1425261 TI - [Regional hyperthermic fibrinolytic perfusion in postoperative deep venous thrombosis of the leg]. AB - Four days after an operation for fusion of lumbar and sacral vertebrae a 30-year old man developed bilateral deep-vein thrombosis in the legs, extending on the left from the fibular group of veins to the popliteal vein. On the right all deep veins of the lower leg were occluded, including the confluence of the popliteal vein. As systemic fibrinolysis was contraindicated, surgical thrombectomy was undertaken. After incomplete removal of the thrombi, regional hyperthermic perfusion with streptokinase was performed using a heart-lung machine. After a compression bandage had been applied to the right leg above the veins the leg was perfused via the common femoral vein at 40 degrees C from the heart-lung machine, at a flow rate of 600-800 ml/min, for 60 min with a solution containing 1 million IU streptokinase. Measurement of various components in the perfusate indicated marked fibrinolysis (fibrinogen: not measurable; fibrinogen breakdown products: > 80 micrograms; streptokinase: 100 FU/ml after 30 min, 62 FU/ml after 60 min). At the same time there was no demonstrable fibrinolytic activity in the systemic circulation. Fibrinogen concentration fell from 340 mg/dl 30 min before the onset of perfusion to 245 mg/dl 90 min after it. After 60 min of perfusion the blood from the right leg was discarded and the leg flushed through with 1.5 l of an electrolyte solution and then filled up with previously obtained and stored patient's own blood concentrate. Subsequent phlebography and venous occlusion plethysmography demonstrated complete recanalization of the deep-vein system with normal venous valve function. PMID- 1425262 TI - [Hyponatremia in heart failure]. PMID- 1425263 TI - [The surgical indications in bacterial endocarditis]. PMID- 1425264 TI - [Juvenile stroke and protein S deficiency]. PMID- 1425265 TI - [Nephrocalcinosis in idiopathic hypercalciuria]. PMID- 1425266 TI - [EEG changes in anorexia nervosa]. PMID- 1425267 TI - [The surgical indications in abdominal aortic aneurysms--from the internal medicine viewpoint]. PMID- 1425268 TI - [Helicobacter pylori-associated gastritis and low-malignancy MALT lymphoma]. PMID- 1425270 TI - [Helicobacter pylori: the local IgA response of the gastric mucosa]. PMID- 1425269 TI - [Multiple myeloma with plasma-cell pericardial tamponade and terminal plasma-cell leukemia]. PMID- 1425271 TI - [Carbohydrate and lipid metabolism following heart bypass operations. The effect of the intravenous hypocaloric administration of glucose versus glucose xylitol (1:1)]. AB - The effect of glucose-xylitol infusion on carbohydrate and lipid metabolism was investigated in 18 metabolically normal men (mean age 56.1 [35-65] years) with coronary heart disease after they had undergone a coronary artery bypass operation. During the first postoperative hours, group I (n = 6) received glucose only (2 mg/kg.min), group II (n = 6) glucose+xylitol (1 mg/kg.min each), and group II a glucose-containing electrolyte solution (0.83 mg/kg.min glucose). Blood glucose and insulin concentrations during the infusion period were significantly (P < 0.05) lower in groups II and III than I (glucose after 6 h: group I 21.5 [15.3-26.8] mmol/l; group II 14.2 [11.2-18.1] mmol/l; group III 12.6 [6.8-16.0] mmol/l). The highest lactate concentrations were reached in group I, 6 hours after the operation. Palmitine and stearine, as well as oleic and linoleic acid concentrations were significantly lower 12 hours postoperatively in group I than groups II and III (P < 0.05). These data indicate that energy-ineffective high glucose concentrations were avoided and endogenous lactate production reduced by the postoperative infusion of glucose+xylitol. In addition, it achieved a higher supply of free fatty acids as energy source to the myocardium without reaching toxic concentrations in the postischaemic myocardium. PMID- 1425272 TI - [The color Doppler-guided compression therapy of a large false aneurysm of the femoral artery following left heart catheterization]. AB - A ventrally located false aneurysm (7 x 5.2 x 3.4 cm) of the right common femoral artery occurred, after left-heart catheterization by the Judkins technique via this artery, in an 83-year-old woman with aortic valve stenosis. Colour Doppler sonography demonstrated a puncture canal (neck of the aneurysm) filling in both systole and diastole, as well as turbulent flow within the aneurysm. Flow into the aneurysm was considerably reduced when the transducer head compressed the aneurysm, while flow continued in the femoral artery and vein. This compression, maintained for 25 min, completely thrombosed the puncture canal and aneurysm so that no vascular surgery was required. PMID- 1425273 TI - [The clinical picture and diagnosis of pulmonary mycoses]. PMID- 1425274 TI - [The individualized therapy of tumors]. PMID- 1425275 TI - [The authorization of hospital physicians on referrals by established colleagues. The judgement of the State Higher Social Court of Rheinland-Pfalz of 19 December 1991]. PMID- 1425276 TI - [The assessment of arrhythmia risks: programmed ventricular stimulation and (or) the detection of ventricular late potentials?]. PMID- 1425277 TI - [Drug-induced cholelitholysis]. PMID- 1425278 TI - [Focal nodular hyperplasia of the liver]. PMID- 1425279 TI - [Therapy-refractory lambliasis in gallbladder involvement]. PMID- 1425280 TI - [The planned extension of MTA training to 3 years]. PMID- 1425281 TI - [Contact lenses and bacterial keratitis]. PMID- 1425282 TI - [Arterial hypertension in older people]. PMID- 1425283 TI - [Morbidity and mortality in type 1 and type 2 diabetes mellitus after the diagnosis of diabetic retinopathy]. AB - One to ten years after laser coagulation for diabetic retinopathy, 229 type I diabetics (mean age 44.3 years) and 157 type II diabetics (mean age 65 years) were re-studied for morbidity and mortality (progression of late damage, duration of survival, cause of death). The duration of diabetes at the first laser coagulation averaged 23.1 years for type I diabetics (15.9 years for type II). Average period from the first laser coagulation to the re-examination was 6.5 years for type I, 5.1 for type II diabetics. Of those patients still alive 6.7% had gone blind (type II: 7.3%). 2.1% and 4.6%, respectively, were receiving dialysis treatment, while renal transplantation had been performed in 3.1 and 1.8%, respectively. Stroke was the most frequent macrovascular complications (8.4 and 16.5%), followed by leg amputation (3.6 and 14.7%) and myocardial infarction (3.7 and 18.3%). 83 patients had died: 35 (15.3%) type I and 48 (30.6%) type II diabetics. Causes of death were septicaemia 14.3% (0%), uraemia 11.4% (8.3%), myocardial infarction 14.3% (33.3%), heart failure 8.6% (29.2%) and stroke 5.7% (6.3%). 10.7% (24.2%) had died within the first 5 years after laser coagulation. Despite a lower incidence of blindness in patients with diabetic retinopathy, the vascular disease progresses in other vascular regions so that a large proportion of diabetics will develop renal failure or die early from macrovascular complications. PMID- 1425284 TI - [Pheochromocytoma as dominant manifestation of v. Hippel-Lindau syndrome]. AB - A diagnosis of von Hippel-Lindau syndrome was made in two families originating from the same part of the Black Forest but apparently unrelated. Nine affected persons (seven males and two females) had a total of 17 tumours: retinal angioma (4), haemangioblastoma of the CNS (1), and phaeochromocytoma (12). Three of the affected persons and eight of the tumours (six phaeochromocytomas, two retinal angiomas) were diagnosed by family screening. Phaeochromocytoma was diagnosed in eight persons; in four it was the only symptomatic lesion. After extensive diagnostic tests the phaeochromocytoma was the sole tumour in four. Despite severe symptoms the diagnosis of von Hippel-Lindau syndrome had not been made prior to the screening examinations because either the common aetiology of the tumour was not known or there was insufficient exchange of information between the two families.--It is recommended that in each case of phaeochromocytoma von Hippel-Lindau syndrome should be excluded so that lesions can be discovered early in other organs and in other affected family members. If the syndrome is present, annual examinations are indicated because of asynchronous and multi-focal tumour growth. PMID- 1425285 TI - [Nephropathy in type 1 diabetes mellitus. Current experimental and clinical aspects]. PMID- 1425286 TI - [Misuse of misoprostol in abortion induction]. PMID- 1425287 TI - [Ergotamine-induced heart valve fibrosis and coronary microangiopathy?]. PMID- 1425288 TI - [Johann Gregor Mendel]. PMID- 1425289 TI - [Gold therapy in chronic polyarthritis]. PMID- 1425290 TI - [By-products of alcoholic fermentation in must production]. PMID- 1425291 TI - [Local lysis therapy in renal artery thrombosis]. PMID- 1425292 TI - [Long-term follow-up after partial resection of a single kidney]. PMID- 1425293 TI - [Mercury concentration in the mouth mucosa of patients with amalgam fillings]. AB - Mercury concentrations were measured in specimens of oral mucosa taken during oral surgery from 90 patients (53 men, 37 women, mean age 42 +/- 16 years); 30 of the patients had no amalgam fillings. All the mucosal specimens extended for at least 2-3 mm from the epithelium of the gingival margin and were clinically and radiologically normal. Thirteen patients without metallic fillings of any kind had mercury concentrations of 118.4 +/- 83.7 ng/g tissue, and in 17 patients with precious metal fillings but no amalgam the mean mercury concentrations were 144 +/- 290 ng/g tissue. Seventeen patients with 1-3 amalgam fillings had an average of 1975 +/- 4300 ng/g tissue and in 26 patients with 3-6 amalgam fillings the average concentration was 1158 +/- 2500 ng/g tissue. In 17 patients with more than six amalgam fillings the mean mercury concentration was 2302 +/- 5600 ng/g tissue. Although these results demonstrate a considerable degree of transfer of mercury from the amalgam fillings to the oral mucosa, it had not resulted in any clinically detectable mucosal lesions. PMID- 1425294 TI - [Recurrent renal colic with passing of horny lamellae. A rare differential diagnosis of renal calculi]. AB - A 64-year-old man reported left-sided renal colics recurring regularly every 5-10 months for the past 25 years. After a typical colic urinary sediment was found to contain brownish, flaky elastic material which histologically consisted of nucleus-free keratoid lamellae. Calcium concentration in serum and urine was normal, as were the serum parathormone (215 pg/l) and inorganic phosphate levels. The intravenous pyelogram revealed a polycyclicly circumscribed filling defect (15 x 20 mm) in the left renal pelvis. At ureteroscopy a lamellar brown-grey tumour was identified which arose from the medial wall of the pelvis. Histological examination demonstrated hyper- and parakeratotic hornified squamous epithelium without malignant degeneration. This finding suggested a cholesteatoma originating from squamous epithelial metaplasia. The tumour was removed endoscopically and the renal wall coagulated by laser, a procedure repeated after 3 months. The patient has been free of symptoms for 3 years. PMID- 1425295 TI - [Leishmaniasis with multiple cutaneous nodules]. AB - Six weeks after a holiday trip to Yugoslavia, a previously well 48-year-old man developed a reddish-livid, firm nodule, 0.5 cm in diameter, on the proximal joint of the right thumb. A similar nodule appeared nearby, as well as over the left patella. Eleven additional nodules occurred over the next 4 months. His general health remained good and physical examination merely noted the liver edge palpable 3 cm below the costal margin. The histology of one of the nodules showed a tuberculoid, plasma-rich inflammatory reaction reminiscent of leishmaniasis or brucellosis. No organisms were seen. Immunohistochemistry of a frozen section demonstrated Leishmania-associated antigens, and the Western-blot test was characteristic for leishmaniasis. No systemic treatment was undertaken because of likely alcoholic toxic liver damage. On local treatment with paromomycin containing ointment the cutaneous nodules healed without scar within 3 months. PMID- 1425296 TI - [Prostaglandin derivatives and antacids in the treatment and prevention of gastroduodenal lesions]. PMID- 1425298 TI - [Settlement questions: Remuneration after outside procedures and radioimmunologic examinations without appropriate procedure approval. Decision of the County Court, Munich, 3/l2/1992]. PMID- 1425297 TI - [New perspectives in immunotherapy: adhesion molecules, superantigens, heat-shock proteins and cytokine antagonists]. PMID- 1425299 TI - [Digitalis intoxication]. PMID- 1425300 TI - [Digitalis intoxication]. PMID- 1425301 TI - [Respiratory and systemic allergies]. PMID- 1425302 TI - [Helicobacter pylori and gastric carcinoma]. PMID- 1425303 TI - [Organ-preserving therapy in invasive bladder carcinoma]. AB - With the aim of organ preservation, transurethral resection with subsequent radiotherapy (until 1985) or combined radio- and chemotherapy (since 1986) was undertaken as part of a prospective trial in 175 consecutive patients (137 men, 38 women; mean age 65 [31-90] years) with invasive bladder carcinoma, tumour stage T1-4 N0-3 M0. All patients had a transurethral resection, followed 2-6 weeks later by definitive radiotherapy at a dose of 50.4 Gy to the bladder in 28 fractions. 85 patients simultaneously with the radiotherapy received chemotherapy with cisplatin (25 mg/m2 daily) or carboplatin (65-75 mg/m2 daily) in the first and fifth weeks of radiotherapy. The 5-year survival rate for the whole group (including inoperable cases) was 50%. The survival rate as related to the T category was 53% for T1 (n = 26), 68% for T2 (n = 34), 45% for T3 (n = 94) and 22% for T4 (n = 17). 139 patients (79%) were left with a normally functioning bladder. Cystectomy was performed in 36 patients because of remaining tumour or recurrence after radiotherapy. Combined radio- and chemotherapy improved the histological remission rate, compared with an earlier control group with radiotherapy only, but it did not affect the survival rate. These data indicate that in advanced bladder carcinoma organ-preserving treatment with transurethral resection and definitive radiotherapy or combined radio- and chemotherapy can be successful. PMID- 1425304 TI - [Complicated aneurysm of the splenic artery]. AB - For 2 1/2 years after sustaining blunt trauma to the abdomen a 51-year-old woman had experienced episodes of pain, recently with throbbing, in the left upper quadrant. A smooth, circumscribed, painless tumour filling the left upper and mid abdomen was palpable under the left costal margin. Ultrasound revealed a 12 x 11 cm space-occupying mass with cystic-fluid components, at first interpreted as a blood-containing pseudocyst. Computed tomography demonstrated a connection with the splenic artery. Digital subtraction angiography established the diagnosis of an aneurysm of the splenic artery arising immediately beyond its origin from the coeliac trunk. Splenectomy and resection of the aneurysm were performed. Total removal of the aneurysm was not undertaken because the dorsal aspect of the aneurysm wall was very thick and fused with the retroperitoneum. The postoperative course was unremarkable. The genesis of splenic aneurysm often remains unexplained. Its occurrence after blunt abdominal trauma is exceedingly rare. PMID- 1425305 TI - [Cholera epidemic in Stettin in the autumn of 1892. Dtsch. med. Wschr. 18 (1892), 1128]. PMID- 1425306 TI - [Perimyocarditis caused by Yersinia enterocolitica serotype 0:3]. AB - Three days after the end of a bout of diarrhoea of 3 days' duration, a 19-year old patient developed severe nocturnal thoracic pain unresponsive to isosorbitol dinitrate. There were no abnormal findings on physical examination, except a sweaty skin. SGOT (38 U/l), creatinine kinase (291 U/l, CK-MB 29 U/l) and lactate dehydrogenase (246 U/l) were all elevated. The ECG showed ST segment elevations in leads I, II, III, aVF and V1-V6 as well as negative terminal T waves in I, II, aVL, AVF and V3-V6, changes suggesting peri- and myocarditis. The Widal test gave a raised antibody titre (1:800) against Yersinia enterocolitica serotype O:3. Seven days later the immunoblot test demonstrated antibodies against the same organism, which was finally isolated from stool after 11 days. Treatment consisted of ciprofloxacin (500 mg twice daily for 14 days). All symptoms, as well as the biochemical and ECG abnormalities, quickly improved. The patient was discharged free of symptoms after 34 days. PMID- 1425307 TI - [Decompression sickness as differential diagnosis in internal medicine emergency admissions]. AB - Two men (aged 37 years--patient 1, and 26 years--patient 2), both in good health, had dived as a sport to a depth of 40 and 45 m, respectively, reportedly keeping to the prescribed decompression times on their ascent. Patient 1 immediately developed shortness of breath and pain in the chest, later neurological deficits in both legs, as well as faecal and urinary incontinence. Examination 60 h later revealed paraparesis, increased leg proprioceptor reflexes and paraesthesia below the 10th thoracic vertebra, with abnormal posterior column function. After recompression (hyperbaric oxygenation, 6 treatment sessions of 4 h each over 8 days, as prescribed in US Navy Table No. 6) the signs improved and two months later there were no deficits. Patient 2 developed 30 min after a similar dive painful, doughy swellings and redness over the upper ventral half of the thorax and both upper arms. All signs and symptoms disappeared after recompression treatment (hyperbaric oxygenation for 3 h), begun 28 h after the dive. Previously elevated levels for haemoglobin (18.5 g/dl), haematocrit (0.56) and red blood corpuscles (5.98 x 10(6)/microliters) returned to normal. The described neurological abnormalities are typical for type II, redness and joint pains for type I decompression sickness. PMID- 1425308 TI - [Clinical features and therapy of persistent ductus arteriosus in adults]. PMID- 1425309 TI - [Diagnosis and prognosis of gonadal damage after chemotherapy and irradiation]. PMID- 1425310 TI - [Organ-preserving therapy of muscle-invasive bladder carcinoma]. PMID- 1425311 TI - [Thrombolytic therapy also in soon occurring second infarct?]. PMID- 1425312 TI - [Congenital giant cell nevus]. PMID- 1425313 TI - [Ondansetron in carcinoid syndrome]. PMID- 1425314 TI - [The pharmacokinetics and bioavailability of acepromazine in the plasma of dogs]. AB - Acepromazine is extensively used in veterinary practice. In dogs, it is used mainly as a preanaesthetic and sedative agent, without the knowledge of pharmacokinetic data in this species. We studied the disposition both after oral and intravenous administration. It was shown, that the sedative effect after an oral dose of 1.3-1.5 mg/kg lasted for about 4 hours. The elimination was slower after oral administration (half-life 15.9 h) than after i. v. injection (half life 7.1 h). The bioavailability of the orally administered drug formulation averaged 20%. The calculation of the pharmacokinetic parameters was performed computer-aided, using conventional compartmental analysis and non-compartmental statistical moment analysis and the results were compared. PMID- 1425315 TI - [In vitro studies of intestinal absorption and biotransformation of furazolidone]. AB - The intestinal biotransformation and absorption of the nitrofuran furazolidone were investigated in isolated gut cells and in the isolated perfused gut. In case of inhibiting furazolidone metabolism by high oxygen tension almost equal concentrations of the parent compound were measured on the mucosal and serosal side of the perfused gut segments. Lowering oxygen supply in order to adjust it to physiological conditions caused a complete degradation of furazolidone in isolated gut cells. Accordingly, hardly any unchanged furazolidone was detected on the serosal side of the isolated perfused gut. An open-chain cyanometabolite was formed in both systems indicating a reductive metabolic process which induces highly reactive intermediates. This metabolite also reached the serosal side of the gut representing the systemic circuit. Thus, the low systemic bioavailability is due to the considerable intestinal metabolism rather than a limited absorption. Unknown metabolites will reach the systemic circuit, the toxic potential of which is still obscure. Independent of its metabolic degradation, thus probably due to its redox cycle furazolidone inhibited intestinal functions as e. g. the flow of water and the transport of sodium. PMID- 1425316 TI - Atypical reactions to halothane in a subgroup of homozygous malignant hyperthermia(MH)-susceptible pigs: indication of a heterogenous genetic basis for the porcine syndrome. AB - Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. In genetically susceptible pigs, MH can be induced by volatile, halogenated anaesthetics such as halothane. Within a series of pharmacological investigations, a fulminant MH could be induced in 59 of 66 homozygous halothane susceptible pigs by a challenge with 3% halothane for 15 minutes. The typical MH was characterized by sudden appearance of tachycardia, muscle rigidity with typical extension of the hindlimbs, increase of body temperature, acidosis-caused by rapid increase of CO2 and lactate production-, hyperkalaemia and increased activity of creatine kinase (CK) and aspartate transaminase (AST). In seven homozygous MH-susceptible pigs, this typical MH could not be induced by halothane. These animals responded with sudden appearance of bradyarrhythmia and decrease of arterial pressure. In these MH-atypical pigs (MHA) neither the typical extension of hindlimbs nor a hyperthermia occurred. Compared to a group of 6 MH-susceptible pigs with typical reactions to halothane (MHS), the biochemical alterations were significantly retarded in MHA-pigs. These atypical reactions to halothane could be the effect of decreased cardiac output. Concerning the atypical reactions, we observed a familiar predisposition in MH susceptible pigs. Although atypical reactions were not found in a group of homozygous halothane-nonsusceptible pigs (MHN), a possible explanation for atypical reactions could be a MH-independent halothane-susceptibility of the myocardium+ in MHA-pigs. On the other side the data may indicate that a primary defect in both the skeletal muscle and also the myocardium is involved in MH. The different reactions to halothane in MH-susceptible pigs could point to a genetic heterogeneity. PMID- 1425317 TI - [Insufficient success in the treatment of epilepsy--mistakes in therapy or resistance to therapy?]. AB - Frequently either no results or inadequate results are obtained in the therapy of canine and feline epilepsy. This is often not due to a primary resistance to therapy, but rather, caused by other factors and, above all, by mistakes made in therapeutic management. The possible causes of a faulty or insufficient treatment and the most common mistakes made in therapeutic regime are described. At the same time suggestions for an optimal course of therapy are given. PMID- 1425318 TI - Acetylsalicylic acid and blood coagulation in the horse. AB - Equine blood may contain salicylic acid (SA) taken up as free acid or represents the metabolite of acetylsalicylic acid (ASA). To obtain information of SA in race horses we screened blood samples of trotting-horses routinely drawn to be analyzed for doping substances. The individual values determined followed a Gaussian distribution displaying a geometric mean of 19 ng SA per ml serum. A probit analysis revealed linear relationship (r = 0.995). Additional studies examined the antithrombotic efficacy of ASA in the horse. An oral dose of 300 mg ASA considerably elevated the bleeding time for more than 2 hours with concomitant SA serum levels between 800 and 1000 ng/ml. It is concluded that salicylate levels even below 1 microgram/ml serum bring about considerable pharmacologic effects such as prolongation of bleeding time, decrease in blood viscosity and possibly dilatation of blood vessels. These effects may improve the tissue supply with blood including oxygen. PMID- 1425319 TI - [The loop diuretic bumetanide as a tool in physiology and pharmacology]. AB - Loop diuretics are derivatives of 4-sulfamoylbenzoic acid, which derived originally from sulfonamides. Their diuretic effect is due to the inhibition of the Na-K-Cl-cotransport system in the distal part of Henle's loop. The compounds react with different affinity with the chloride binding site of the transporter. Bumetanide is among the most potent blockers with an IC50 of 0.2 microM. The compound was developed by P. W. FEIT, 1971; the saluretic response was described first by H. H. FREY 1972. Bumetanide has outgrown to become a tool for physiologists and pharmacologists in renal transport research. The compound has essentially contributed to the elucidation of the mechanisms of volume regulation of cells. Bumetanide is taken up into tubule cells and hepatocytes by active transport. The uptake in tubule cells ist mediated by an organic anion transporter, which is involved in the renal secretion of drugs. In the liver bumetanide is transporter by the bile acid carrier. The carrier is a multispecific drug transporter, too. It is not yet known, whether both drug transport systems contain identical membrane proteins. For this purpose bumetanide is currently used to investigate by photoaffinity labeling and functional expression cloning molecular principles of the drug elimination in kidney and liver. PMID- 1425320 TI - [The metabolism of albendazole in the isolated perfused intestine of rats]. AB - Pharmacokinetic studies on Albendazole after peroral administration demonstrate a rapid and complete biotransformation. The major metabolites Albendazole sulphoxide and -sulphone were detected in the plasma; the parent compound was only found sporadically at very low levels. These results indicate removal by the liver and/or the gut at first pass. After evidence is found that the liver has the capacity to sulphoxidize and to sulphonize Albendazole, biotransformation of the gut was examined using an isolated perfused rat gut model. A high-performance liquid chromatography method was used to simultaneously determinate Albendazole, sulphoxide and -sulphone. Albendazole was biotransformed partly to Albendazole sulphoxide by the gut, whereby the metabolite but not the parent compound was absorbed. It is concluded, that the gut has the capacity to biotransform Albendazole. However, biotransformation is limited to the first step, the sulphoxidation. PMID- 1425322 TI - [The problems of the so-called Arteria carotis externa (= ventralis) of the Anamniota. I. Comparative literature analysis]. AB - The study discusses problems as related to the existence of a so-called A. carotis externa (= ventralis) in the Anamnia, and is based on the analysis of old and new literature. The facts presented are illustrated by several figures, demonstrating the organization pattern of branchial arteries and their various branches in adult animals as well as during the development of all types of branchial vessels. Summarizing the aspects involved, it can be concluded that an A. carotis ventralis does not exist, neither in reality nor as the first stage of an A. carotis externa. All of the efferent vessels coming from the 6 original branchial arteries, always arise from the respective A. branchialis efferens and contain oxygenated blood. As A. hypobranchialis lateralis and medialis these vessels supply the entire hypobranchial region, the floor of the mouth, and the heart. Moreover, a rostral prolongation of the Aorta ventralis is also not proven to exist during the ontogenesis of branchial arches. PMID- 1425321 TI - [Effect of etretinate on the activity of intestinal disaccharidases]. AB - The retinoid etretinate influences the proliferation and differentiation of epithelial cells. Therefore, the activity of disaccharidases maltase and sucrase was measured in duodenum and jejunum after oral retinoid application to female mice. The enzymes are localized in the brush border of differentiating mucosal cells. The etretinate dose ranged from 0.1 to 1 mg/kg. The treatment with etretinate induced a decrease of the duodenal and jejunal disaccharidase activity. A correlation between the influence in intestinal enzyme activity and undesired gastrointestinal side effects which were described by GOLD et al. (1988) is supposed. PMID- 1425323 TI - [Electrophoretic studies of serum protein fractions in horses with laminitis]. AB - The spectrum of serum proteins was evaluated in 46 horses affected with spontaneous laminitis and correlations between the severity of the disease and changes of the protein pattern were analyzed. The investigation was made in two groups; group A consisted of 21 horses of various breeds (warmblood, thoroughbred, standardbred) and group B of 25 ponys. Each group was subdivided according to the severity of the disease, using the OBEL-grade (OG) classification system. Serum proteins were separated by different one- and two dimensional electrophoretic methods. Sera analysed by cellulose acetate electrophoresis showed a significant difference in the alpha 1-globulin fraction between OG II and OG IV affected horses. An increasing severity of the disease was correlated with a decrease of the alpha 1-globulins. The other protein fractions didn't show a uniform tendency. In group B there was a significant difference in the alpha 1-globulin fractions of OG II and OG III and in the beta 2-globulin fractions of OG I and OG II affected ponys. The acute phase proteins C3c, C4, Hp and fibronectin could be determined in a preliminary study in horse serum using the cross-reactivity of antibodies against the homologous human proteins. PMID- 1425324 TI - [Biology, pathogenicity, diagnosis and control of Ancylostoma caninum]. AB - Infections with Ancylostoma caninum are transmitted orally or percutaneously. The transmission of infectious stages with the milk of particular importance for the distribution of the species. It occurs during the dissemination of larvae that follows every infection as well as after reactivation of resting somatic larvae in the bitch at the end of the pregnancy. The galactogenic transmission of larvae occurs even when, due to existing immunity, no patent infections develop in the bitch. Immunity does not or only to a low extent influence impatient infections or the migration of reactivated somatic larvae. It also allows a limited reestablishment of a deposit of larvae in the bitch. Following percutaneous infection dermatitis occurs in the area of larval penetration and the lung is affected by migrating larvae. Intestinal stages of Ancylostoma caninum damage the host by ingestion of the mucosa of the small intestine and withdrawal of blood. Main symptoms of ancylostomiasis are a mucous haemorrhagic diarrhoea and anaemia, that become visible 8 to 10 days post infection. The examination for impatient infections with Ancylostoma caninum can be done by immunofluorescence and ELISA. With both methods antibodies against third stage larvae can be detected from the first or second week post infection onward. Patent infections with Ancylostoma caninum can easily be detected by faecal examination for the presence of the characteristic oval, thin-walled eggs containing few blastomeres. Galactogenic infections with Ancylostoma caninum can be prevented or reduced by a regular treatment of the bitch with albendazole, fenbendazole or oxfendazole during the activation of larvae in the last third of the pregnancy or by repeated treatment with ivermectin shortly before and after birth. To prevent patent infections, galactogenic infected puppies have to be treated early and repeatedly. PMID- 1425325 TI - [Toxic effects in rabbits after immunization against the pyrrolizidine alkaloid retrorsine]. AB - Six rabbits were immunized against the pyrrolizidine alkaloid retrorsin, conjugated to bovine serum albumin. Seven i.v. inoculations were distributed over a period of half a year. The total antigen dose differed between animals. Towards the end of the experiment all animals (except 2 receiving the lowest antigen dose) suffered from apathy, anorexia and loss of body weight. Pathologically these symptoms correlated well with liver cirrhosis, gradually dependent on the total antigen dose. Blood-chemical parameters were disparate and contradictory. PMID- 1425326 TI - [Husbandry factors causing morphologic abnormalities in poultry meat (broilers)]. AB - Zootechnical events affect the state of slaughtered poultry. Data from the literature are compiled. From this point of view monitoring of environmental parameters and morphological findings observed in the slaughterhouse can help in detecting faults in the fattening period. An approach like this would contribute to quality control in broiler meat production. PMID- 1425327 TI - [The immunization of pheasants against Newcastle disease]. AB - ND-Adsorbatvakzine "Dessau" and Lasovak are well effective and tolerated in pheasants as immuno-prophylactic methods against Newcastle disease infection. Lasovak produces higher titres of antibodies and better rates of protection. The antibodies are created quicker too and reduced more slowly. There is no correlation between the average of antibody level and rate of protection after experimental infection. Even if antibodies are not demonstrable in hemagglutination inhibition test there is still existing a satisfactory protection. After two vaccinations in the age of chickens in 3 to 4 weeks interval and repetition after always 16 weeks pheasants can be protected effectively for the rearing and breeding seasons. PMID- 1425328 TI - [Effects of lowest levels of drugs--a contribution to homeopathy research]. AB - After oral administration of homoeopathically prepared low-dose-amounts of Conium and Mercury phosphate to male Wistar rats enzymatic parameters were investigated in three subcellular compartments of the liver under blind conditions. 1. After seven single application of the substance amount referring to a D8 potency a maximum effect could be detected for both agents. 2. The relation between agent and magnitude of the provoked effect is not linear. 3. The importance of these results is discussed and integrated into a general context. PMID- 1425329 TI - [Evaluation from a food regulatory aspect of tuberculous slaughtered cattle at the end of the 18th century--together with a study of the position of the veterinarian in public service at that time]. AB - A decree of the Hannoverian sovereign GEORGE III passed in 1787 regarding the treatment of slaughtering cattle affected with tuberculous changes of the pleura is presented. Special emphasis is placed on the practice of food hygiene at that time and on the fact that the veterinarian was regarded an equal expert compared to the physician. PMID- 1425330 TI - [Short report: rinderpest in Turkey 1991/92]. PMID- 1425331 TI - Asymmetrical retinoic acid synthesis in the dorsoventral axis of the retina. AB - An aldehyde dehydrogenase present at high levels in the dorsal retina of the embryonic and adult mouse was identified as the isoform AHD-2 known to oxidize retinaldehyde to retinoic acid. Comparative estimates of retinoic acid levels with a reporter cell line placed the retinas among the richest tissues in the entire body of the early embryo; levels in ventral retina, however, exceeded dorsal levels. Retinoic acid synthesis from retinaldehyde in the dorsal pathway was less effective than the ventral pathway at low substrate levels and more effective at high levels. The dorsal pathway was preferentially inhibited by disulfiram, while ventral synthesis was preferentially inhibited by p hydroxymercuribenzoate. When protein fractions separated by isoelectric focusing were analyzed for retinoic acid synthesizing capacity by a zymography-bioassay, most of the synthesis in dorsal retina was found to be mediated by AHD-2, and ventral synthesis was mediated by dehydrogenase activities distinct in charge from AHD-2. Postnatally, levels of highest retinoic acid synthesis shifted from ventral to dorsal retina. In the adult retina, the dorsal pathway persisted, but the preferential ventral pathway was no longer detectable. Our observations raise the possibility that retinoic acid plays a role in the determination and maintenance of the dorsoventral axis of the retina, and that the morphogenetically significant asymmetry here lies in the spatial arrangement of synthetic pathways. PMID- 1425332 TI - beta-D xyloside alters dermatan sulfate proteoglycan synthesis and the organization of the developing avian corneal stroma. AB - Corneal transparency is dependent upon the development of an organized extracellular matrix containing small diameter collagen fibrils with regular spacing, organized as orthogonal lamellae. Proteoglycan-collagen interactions have been implicated in the regulation of collagen fibrillogenesis and matrix assembly. To determine the role of dermatan sulfate proteoglycan in the development and organization of the secondary corneal stroma, its synthesis was disrupted using beta-D xyloside. The secondary corneal stroma contains two different proteoglycans, dermatan sulfate and keratan sulfate proteoglycan. beta D xyloside interferes with xylose-mediated O-linked proteoglycan synthesis, and thus disrupts dermatan sulfate proteoglycan synthesis. Corneal keratan sulfate proteoglycan, a mannose-mediated N-linked proteoglycan, should not be altered. Biochemical analysis of corneas treated both in vitro and in ovo revealed a reduced synthesis of normally glycosylated dermatan sulfate proteoglycans and an increased synthesis of free xyloside-dermatan sulfate glycosaminoglycans. Keratan sulfate proteoglycan synthesis was unaltered in both cases. Corneal stromas were studied using histochemistry and electron microscopy after in ovo treatment with beta-D xyloside. The observed biochemical alterations in dermatan sulfate proteoglycans translated into disruptions in the organization of beta-D xyloside treated stromas. There was a reduction in the histochemical staining of proteoglycans, but no alteration in collagen fibril diameter. In addition, focal alterations in collagen fibril packing, and a disruption of lamellar organization were observed in beta-D xyloside-treated corneas. These data suggest that dermatan sulfate proteoglycans are not involved in the regulation of corneal collagen fibril diameter, but are important in the fibril-fibril spacing as well as in lamellar organization, and cohesiveness. PMID- 1425333 TI - A transgene containing lacZ is expressed in primary sensory neurons in zebrafish. AB - In order to screen for developmentally active chromosomal domains during zebrafish embryogenesis, we generated transgenic fish by microinjecting two different lacZ reporter constructs into fertilized eggs. Transgenic fish were screened among the progeny of injected fish (F0) crossed to non-injected fish. Groups of 15 to 20 progeny of each cross were tested for lacZ expression and/or transmission of injected sequences using PCR and Southern hybridizations. Progeny from 2 of 102 fish injected with supercoiled constructs containing Rous sarcoma virus promoter sequences showed apparently spatially regulated beta-galactosidase (beta-Gal) activity. However, we were not able to detect this reporter construct in DNA from fins of F1 fish. Injections of a linear reporter construct containing mouse heat-shock promoter sequences revealed transmission of injected sequences to F1 progeny in about 6% of cases (8 of 129 fish, tested with PCR). We found one lacZ-expressing line that showed a spatially and temporally restricted expression of lacZ and, therefore, features typical characteristics of "enhancer trap" lines. In this line, lacZ expression starts at 16 hours post-fertilization in trigeminal ganglion cells. At about 24 hours lacZ expression can be detected in trigeminal ganglion neurons and Rohon-Beard neurons, indicating that the development of these two cell types shows common features. The reporter gene has integrated as a single copy. The founder fish was mosaic: 19% of its offspring (3 of 16 tested animals) carried the reporter construct in their fins; about 51% (13 of 27 tested animals) of the progeny of F1 fish were beta-Gal positive indicating full hemizygosity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425335 TI - Analysis of Xwnt-4 in embryos of Xenopus laevis: a Wnt family member expressed in the brain and floor plate. AB - This study characterizes the temporal and spatial expression during early Xenopus development of Xwnt-4, a member of the Wnt gene family. The Xwnt-4 protein contains all of the sequence motifs that are hallmarks of the Wnt gene family and is 84% identical to the mouse homolog, Wnt-4. The highest level of Xwnt-4 expression occurs during the early neurula stage of development although its expression persists throughout embryogenesis and can be found in the adult testis, brain and epithelium. Consistent with its localization to head and dorsal regions of microdissected embryos, the expression of Xwnt-4 is enhanced in anterodorsalized embryos resulting from treatment with LiCl, and the expression of Xwnt-4 is suppressed in UV-ventralized embryos that lack anterior neural tissue. These results suggested that expression of Xwnt-4 is dependent on the induction of neural tissue. This idea was tested using induction experiments with dorsal or ventral ectoderm from a stage 10 embryo, recombined with dorsal marginal zone mesoderm from the same embryo. Recombinant tissue and ectoderm alone were cultured until stage 14, when Xwnt-4 expression was assayed using Northern analysis. In the recombinant assay, Xwnt-4 expression does not occur in the uninduced ectoderm but is expressed in both the dorsal and ventral recombinants. Xwnt-4 expression in neural ectoderm was confirmed in isolated, induced neural ectoderm, dissected away from the dorsal mesoderm, in a stage 12.5 embryo. Whole-mount in situ hybridization confirmed the dissection studies and demonstrated that Xwnt-4 transcripts are expressed in the dorsal midline of the midbrain, hindbrain and the floor plate of the neural tube. Collectively, the data indicate that Xwnt-4 is a unique member of the Wnt family whose expression is dependent on neural induction. The specific pattern of expression following neural induction suggests that Xwnt-4 plays a role in the early patterning events responsible in the formation of the nervous system in Xenopus. PMID- 1425334 TI - Spatial and temporal expression of an epithelial mucin, Muc-1, during mouse development. AB - The Muc-1 mucin is found as a transmembrane protein in the apical surface of glandular epithelia. To provide insight into possible functions, we have assessed the timing of expression and the distribution of the Muc-1 protein during mouse embryogenesis using three different techniques: RT-PCR, northern blots and immunohistochemistry. Our results indicate that Muc-1 expression correlates with epithelial differentiation in stomach, pancreas, lung, trachea, kidney and salivary glands. Once started, Muc-1 synthesis continually increases with time, mainly due to epithelial area growth. Our data suggest that expression of the Muc 1 gene is under spatial and temporal control during organogenesis. Although Muc-1 is present in different organs, its expression is not induced systemically, but according to the particular onset of epithelial polarization and branching morphogenesis of each individual organ. It is of particular interest that Muc-1 protein can be detected lining the apical surfaces of the developing lumens when the epithelium of these organs is still undergoing folding and branching, and glandular activity has not yet started. We speculate that Muc-1 may participate in epithelial sheet differentiation/lumen formation during early development of the organs known to express it. This speculation is based on: (1) the detection of Muc-1 expression early during organogenesis, (2) the defined apical localization in different epithelia, (3) the decrease in cell-cell interactions when Muc-1 protein is highly expressed and (4) the possible interaction of its cytoplasmic tail with the actin cytoskeleton. However, it remains to be established using in vitro systems, whether the temporal and local expression of the Muc-1 gene coincident with the morphogenetic events described here is relevant for the process. PMID- 1425336 TI - Isolation and expression of two novel Wnt/wingless gene homologues in Drosophila. AB - Wingless (wg), the Drosophila homologue of the mouse Wnt-1 proto-oncogene, is a segment polarity gene essential in each segment for normal Drosophila development. We here report the isolation of two novel Drosophila Wnt homologues, DWnt-2 and DWnt-3, and thus the existence of a Wnt/wingless gene family in Drosophila. DWnt-2 and DWnt-3 map to chromosome 2 position 45E and chromosome X position 17A/B, respectively. DWnt-2 and DWnt-3, like the other known Wnt genes, encode amino-terminal signal peptides suggesting that the gene products are secreted proteins. The putative translation product of DWnt-2 and the carboxy terminal half of the deduced DWnt-3 product are both rich in conserved cysteine residues. In comparison with other Wnt gene products, mostly about 40 x 10(3) relative molecular mass, the DWnt-3 protein has an extended amino terminus and a long internal insert, and its predicted relative molecular mass is 113 x 10(3). The expression patterns of these two Wnt/wg homologues are dynamic during Drosophila embryogenesis. The distribution of DWnt-2 transcripts is predominantly segmented, with the additional presence of transcripts in the presumptive gonads. Transcripts of both DWnt-2 and DWnt-3 appear to be associated with limb primordia in the embryo and may therefore specify limb development. DWnt-3 is also expressed in mesodermal and neurogenic regions. The distribution of DWnt-3 transcripts in cells of the central nervous system (CNS) during Drosophila embryogenesis suggests that DWnt-3 could be involved in CNS development. PMID- 1425337 TI - Analysis of glia cell differentiation in the developing chick peripheral nervous system: sensory and sympathetic satellite cells express different cell surface antigens. AB - To identify and analyse precursor cells of neuronal and glial cell lineages during the early development of the chick peripheral nervous system, monoclonal antibodies were raised against a population of undifferentiated cells of E6 dorsal root ganglia (DRG). Non-neuronal cells of E6 DRG express surface antigens that are recognized by four monoclonal antibodies, G1, G2, GLI 1 and GLI 2. The proportion of non-neuronal cells in DRG that express the GLI 1 antigen is very high during ganglion formation (80% at E4) and decreases during later development (15% at E14). GLI 2 antigen is expressed only on a minority of the cells at E6 and increases with development. The G1 and G2 antigens are expressed on about 60 80% of the cells between E6 and E14. All cells that express the established glia marker O4 are also positive for the new antigens. In addition, it was demonstrated that GLI 1-positive cells from early DRG, which are devoid of O4 antigen, could be induced in vitro to express the O4 antigen. Thus, the antigen positive cells are considered as glial cells or glial precursor cells. Surprisingly, the antigen expression by satellite cells of peripheral ganglia is dependent on the type of ganglion: antigens G1, G2 and GLI 1 were not detectable on glial cells of lumbosacral sympathetic ganglia and GLI 2 was expressed only by a small subpopulation. These results demonstrate an early immunological difference between satellite cells of sensory DRG and sympathetic ganglia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425338 TI - Gynandromorphs of Drosophila suggest one common primordium for the somatic cells of the female and male gonads in the region of abdominal segments 4 and 5. AB - In mosaic gonads of gynandromorphs of Drosophila, the amount of female and the amount of male somatic tissues add up to roughly one unit. This suggests that the somatic component of the gonads in males and females derives from a single common primordium, i.e. testes and ovaries appear to be homologous. Fate-mapping places this primordium ventrally of the sternites into the mesodermal region of the fourth and fifth abdominal segment. This location is corroborated by the observation that defects in and around abdominal segment 4 and absence of the gonads are strongly correlated in animals damaged by the mutation osk301. Gonads were mosaic with a frequency of 10.5% which indicates that the gonadal primordium originates from about 10 progenitor cells, and together with other evidence, suggests that these progenitor cells are located within a single segment (or parasegment). PMID- 1425339 TI - PDGF receptors in the rat CNS: during late neurogenesis, PDGF alpha-receptor expression appears to be restricted to glial cells of the oligodendrocyte lineage. AB - Using in situ hybridization, we have visualized cells in the rat central nervous system (CNS) that contain mRNA encoding the platelet-derived growth factor alpha receptor (PDGF-alpha R). After embryonic day 16 (E16), PDGF-alpha R mRNA appears to be expressed by a subset of glial cells, but not by neurons. The temporal and spatial distribution of PDGF-alpha R+ cells, together with 125I-PDGF binding studies on subsets of glial cells in vitro, suggests that PDGF-alpha R may be expressed predominantly, or exclusively, by cells of the oligodendrocyte-type-2 astrocyte (O-2A) lineage. This conclusion is supported by the fact that the numbers of PDGF-alpha R+ cells in developing and adult optic nerves correlate well with independent estimates of the number of O-2A progenitor cells in the nerve at equivalent ages. Small numbers of PDGF-alpha R+ cells are present in the brain at E16, at which time they are found outside the subventricular germinal zones, suggesting that these cells do not express PDGF-alpha R until after, or shortly before they start to migrate away from the subventricular layer towards their final destinations. Reduced numbers of PDGF-alpha R+ cells persist in the adult CNS. PDGF-alpha R is also expressed strongly in the meningeal membranes and choroid plexus, and in the inner limiting membrane of the retina. PMID- 1425340 TI - Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. AB - The mesoderm of amphibian embryos such as Xenopus laevis arises through an inductive interaction in which cells of the vegetal hemisphere of the embryo act on overlying equatorial and animal pole cells. Three classes of 'mesoderm inducing factor' (MIF) that might be responsible for this interaction in vivo have been discovered. These are members of the transforming growth factor type beta (TGF-beta), fibroblast growth factor (FGF) and Wnt families. Among the most potent MIFs are the activins, members of the TGF-beta family, but RNA for activin A and B is not detectable in the Xenopus embryo until neurula and late blastula stages, respectively, and this is probably too late for the molecules to act as natural inducers. In this paper, we use the polymerase chain reaction to clone additional members of the TGF-beta family that might possess mesoderm-inducing activity. We show that transcripts encoding Xenopus bone morphogenetic protein 4 (XBMP-4) are detectable in the unfertilized egg, and that injection of XBMP-4 RNA into the animal hemisphere of Xenopus eggs causes animal caps isolated from the resulting blastulae to express mesoderm-specific markers. Surprisingly, however, XBMP-4 preferentially induces ventral mesoderm, whereas the closely related activin induces axial tissues. Furthermore, the action of XBMP-4 is 'dominant' over that of activin. In this respect, XBMP-4 differs from basic FGF, another ventral inducer, where simultaneous treatment with FGF and activin results in activin-like responses. The dominance of XBMP-4 over activin may account for the ability of injected XBMP-4 RNA to 'ventralize' whole Xenopus embryos. It is interesting, however, that blastopore formation in such embryos can occur perfectly normally. This contrasts with embryos ventralized by UV-irradiation and suggests that XBMP-4-induced ventralization occurs after the onset of gastrulation. PMID- 1425341 TI - Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis. AB - Adult rat pelage follicle dermal papilla cells induced follicle neogenesis and external hair growth when associated with adult footpad skin epidermis. They thus demonstrated a capacity to completely change the structural arrangement and gene expression of adult epidermis--an ability previously undocumented for cultured adult cells. Isolation chambers ensured that de novo follicle formation must have occurred by eliminating the possibility of cellular contributions, and/or inductive influences, from local skin follicles. These findings argue against previous suggestions of vibrissa follicle specificity, and imply that the potential for hair follicle induction may be common to all adult papilla cells. PMID- 1425342 TI - Activation of the easter zymogen is regulated by five other genes to define dorsal-ventral polarity in the Drosophila embryo. AB - The product of the Drosophila easter gene, a member of the trypsin family of serine proteases, must be more active ventrally than dorsally to promote normal embryonic polarity. The majority of the easter protein in the embryo is present in the unprocessed zymogen form and appears to be evenly distributed in the extracellular space, indicating that the asymmetric activity of wild-type easter must arise post-translationally. A dominant mutant form of easter that does not require cleavage of the zymogen for activity (ea delta N) is active both dorsally and ventrally. The ea delta N mutant bypasses the requirement for five other maternal effect genes, indicating that these five genes exert their effects on dorsal-ventral patterning solely by controlling the activation of the easter zymogen. We propose that dorsal-ventral asymmetry is initiated by a ventrally localized molecule in the vitelline membrane that nucleates an easter zymogen activation complex, leading to the production of ventrally active easter enzyme. PMID- 1425343 TI - DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction. AB - Establishment of mesodermal tissues in the amphibian body involves a series of inductive interactions probably elicited by a variety of peptide growth factors. Results reported here suggest that mesodermal patterning involves an array of signalling molecules including DVR-4, a TGF-beta-like molecule. We show that ectopic expression of DVR-4 causes embryos to develop with an overall posterior and/or ventral character, and that DVR-4 induces ventral types of mesoderm in animal cap explants. Moreover, DVR-4 overrides the dorsalizing effects of activin. DVR-4 is therefore the first molecule reported both to induce posteroventral mesoderm and to counteract dorsalizing signals such as activin. Possible interactions between these molecules resulting in establishment of the embryonic body plan are discussed. PMID- 1425344 TI - A maternal factor, OZ-1, activates embryonic transcription of the Xenopus laevis GS17 gene. AB - We describe the identification of an enhancer sequence and a sequence-specific DNA-binding protein required for developmental expression of the Xenopus laevis GS17 gene. Using microinjection of recombinant plasmids into fertilized frog eggs, we have shown that a 14 base pair CT-rich sequence element, normally located about 700 bases upstream of the GS17 promoter, is sufficient to activate transcription of a heterologous reporter gene in gastrula stage embryos. This regulatory element has been called the OZ sequence. Sequences closely related to OZ are located in the promoter regions of several other genes expressed during Xenopus development. Extracts prepared from Xenopus embryos show the presence of a DNA-binding factor, OZ-1, that specifically recognizes the OZ sequence. Mutations within the OZ element that abolish OZ-1 binding also abolish enhancer activity. The OZ-1 factor contains at least two proteins of approximate M(r) 76 x 10(3) and 100 x 10(3). The sequence-specific binding activity accumulates during oogenesis and remains present at approximately constant levels throughout early development. PMID- 1425345 TI - The neural tube/notochord complex is necessary for vertebral but not limb and body wall striated muscle differentiation. AB - The aim of this work was to investigate the role played by the axial organs, neural tube and notochord, on the differentiation of muscle cells from the somites in the avian embryo. Two of us have previously shown that neuralectomy and notochordectomy is followed by necrosis of the somites and consecutive absence of vertebrae and of most muscle cells derived from the myotomes while the limbs develop normally with muscles. Here we have focused our attention on muscle cell differentiation by using the 13F4 mAb that recognizes a cytoplasmic antigen specific of all types of muscle cells. We show that differentiation of muscle cells of myotomes can occur in the absence of notochord and neural tube provided that the somites from which they are derived have been in contact with the axial organs for a defined period of time, about 10 hours for the first somites formed at the cervical level, a duration that progressively reduces caudalward (i.e. for thoracic and lumbar somites). Either one or the other of the two axial organs, the neural tube or the notochord can prevent somitic cell death and fulfill the requirements for myotomal muscle cell differentiation. Separation of the neural tube/notochord complex from the somites by a surgical slit on one side of the embryo gave the same results as extirpation of these organs and provided a perfect control on the non-operated side. A striking finding was that limb and body wall muscles, although derived from the somites, differentiated in the absence of the axial organs. However, limb muscles that develop after excision of the neural tube started to degenerate from E10 onward due to lack of innervation. In vitro explantation of somites from different axial levels confirmed and defined precisely the chronology of muscle cell commitment in the myotomes as revealed by the in vivo experiments. PMID- 1425346 TI - Synaptic basal lamina contains a signal for synapse-specific transcription. AB - Nuclei in the synaptic region of multinucleated skeletal myofibers are transcriptionally distinct, since acetylcholine receptor genes are transcribed at a high rate by these nuclei, but not by nuclei elsewhere in the myofiber. Although this spatially restricted transcription pattern is presumably imposed by the motor nerve, the continuous presence of the nerve is not required, since synapse-specific transcription persists after denervation. These results suggest either that a transcriptional signal persists at synaptic sites after nerve terminals have degenerated, or that a transcriptional pattern in the myofiber, once established, is stable in the absence of a nerve-derived signal. To distinguish between these possibilities, we denervated muscle and damaged the myofibers and specialized cells located near synaptic sites, and then studied transcription of an acetylcholine receptor gene in myofibers that regenerated in their original basal lamina sheaths, but remained denervated. We show that synapse-specific transcription is re-induced in these regenerated myofibers, and we conclude that a signal for synapse-specific transcription is stably maintained in the synaptic basal lamina. PMID- 1425347 TI - Ventral ectoderm of Xenopus forms neural tissue, including hindbrain, in response to activin. AB - The peptide growth factor Activin A has been shown to induce complete axial structures in explanted blastula animal caps. However, it is not understood how much this response to activin depends upon early signals that prepattern the ectoderm. We have therefore asked what tissues can be induced in blastula animal caps by activin in the absence of early dorsal signals. Using whole-mount in situ hybridization, we compare the expression of three neural markers, N-CAM, En-2 and Krox-20 in activin-treated ectoderm from control and ventralized embryos. In response to activin, both normal and ventralized animal caps frequently form neural tissue (and express N-CAM) and express the hindbrain marker Krox-20. However, the more anterior marker, En-2, is expressed in only a small fraction of normal animal caps and rarely in ventralized animal caps; the frequency of expression does not increase with higher doses of activin. In all cases En-2 and Krox-20 are expressed in coherent patches or stripes in the induced caps. Although mesoderm is induced in both control and ventralized animal caps, notochord is found in response to activin at moderate frequency in control caps, but rarely in ventralized animal caps. These results support the idea that in the absence of other signals, activin treatment elicits hindbrain but not notochord or anterior neural tissue; and thus, the anterior and dorsal extent of tissues formed in response to activin depends on a prior prepatterning or previous inductions. PMID- 1425348 TI - Activin can generate ectopic axial structures in chick blastoderm explants. AB - We have recently shown that activin can induce the formation of axial structures from chick blastulae and that activin beta-B is transcribed, in the hypoblast of the chick, at the same stage that axial mesoderm is being induced. It was not clear, however, whether activin was merely allowing the central epiblastic cells to express a differentiated phenotype for which they were already prepared. This report shows that activin-containing medium (ACM) can act as an instructive inductor, which can change the fate of competent cells and bring about the formation of an ectopic embryonic axis. Furthermore, we show data that suggest that during normal development only one axis is obtained as a result of a carefully controlled inhibitory process. PMID- 1425349 TI - Developmental expression of the Xenopus int-2 (FGF-3) gene: activation by mesodermal and neural induction. AB - We have used a probe specific for the Xenopus homologue of the mammalian proto oncogene int-2 (FGF-3) to examine the temporal and spatial expression pattern of the gene during Xenopus development. int-2 is expressed from just before the onset of gastrulation through to prelarval stages. In the early gastrula, it is expressed around the blastopore lip. This is maintained in the posterior third of the prospective mesoderm and neuroectoderm in the neurula. A second expression domain in the anterior third of the neuroectoderm alone appears in the late gastrula, which later resolves into the optic vesicles, hypothalamus and midbrain hindbrain junction region. Further domains of expression arise in tailbud to prelarval embryos, including the stomodeal mesenchyme, the endoderm of the pharyngeal pouches and the cranial ganglia flanking the otocyst. It is shown, by treatment of blastula ectoderm with bFGF and activin, that int-2 can be expressed in response to mesoderm induction. By heterotypic grafting of gastrula ectoderm into axolotl neural plate, we have also demonstrated that int-2 can be expressed in response to neural induction. These results suggest that int-2 has multiple functions in development, including an early role in patterning of the anteroposterior body axis and a later role in the development of the tail, brain derived structures and other epithelia. PMID- 1425350 TI - The somitogenetic potential of cells in the primitive streak and the tail bud of the organogenesis-stage mouse embryo. AB - The developmental potency of cells isolated from the primitive streak and the tail bud of 8.5- to 13.5-day-old mouse embryos was examined by analyzing the pattern of tissue colonization after transplanting these cells to the primitive streak of 8.5-day embryos. Cells derived from these progenitor tissues contributed predominantly to tissues of the paraxial and lateral mesoderm. Cells isolated from older embryos could alter their segmental fate and participated in the formation of anterior somites after transplantation to the primitive streak of 8.5-day host embryo. There was, however, a developmental lag in the recruitment of the transplanted cells to the paraxial mesoderm and this lag increased with the extent of mismatch of developmental ages between donor and host embryos. It is postulated that certain forms of cell-cell or cell-matrix interaction are involved in the specification of segmental units and that there may be age-related variations in the interactive capability of the somitic progenitor cells during development. Tail bud mesenchyme isolated from 13.5-day embryos, in which somite formation will shortly cease, was still capable of somite formation after transplantation to 8.5-day embryos. The cessation of somite formation is therefore likely to result from a change in the tissue environment in the tail bud rather than a loss of cellular somitogenetic potency. PMID- 1425352 TI - Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development. AB - The Notch gene of Drosophila encodes a large transmembrane protein involved in cell-cell interactions and cell fate decisions in the Drosophila embryo. To determine if a gene homologous to Drosophila Notch plays a role in early mouse development, we screened a mouse embryo cDNA library with probes from the Xenopus Notch homolog, Xotch. A partial cDNA clone encoding the mouse Notch homolog, which we have termed Motch, was used to analyze expression of the Motch gene. Motch transcripts were detected in a wide variety of adult tissues, which included derivatives of all three germ layers. Differentiation of P19 embryonal carcinoma cells into neuronal cell types resulted in increased expression of Motch RNA. In the postimplantation mouse embryo Motch transcripts were first detected in mesoderm at 7.5 days post coitum (dpc). By 8.5 dpc, transcript levels were highest in presomitic mesoderm, mesenchyme and endothelial cells, while much lower levels were detected in neuroepithelium. In contrast, at 9.5 dpc, neuroepithelium was a major site of Motch expression. Transcripts were also abundant in cell types derived from neural crest. These data suggest that the Motch gene plays multiple roles in patterning and differentiation of the early postimplantation mouse embryo. PMID- 1425351 TI - Developmental regulation of villin gene expression in the epithelial cell lineages of mouse digestive and urogenital tracts. AB - The expression of villin, an actin-binding protein and major structural component of the brush border of specialized absorptive cells, was studied during mouse embryogenesis. We show that the ontogeny of villin expression is limited to the epithelial cell lineages of the digestive and uro-genital tracts and accounts for the tissue-specific expression observed in adult mice. This spatiotemporal pattern of villin expression is distinctive in sequence, intensity, regional distribution and polarization. During the development of the primitive gut, villin is faintly and discontinuously expressed in the invaginating foregut but it is expressed in every cell bordering the hindgut pocket. Later, villin expression increases along the developing intestine and concentrates in the brush border of the epithelium bordering the villi. In gut derivatives, villin is present in liver and pancreas primordia but only biliary and pancreatic cells maintain a faint villin expression as observed in adults. In the urogenital tract, mesonephric tubules are the first mesodermal derived structures to express villin. This expression is maintained in the ductuli efferents, paradidymis and epoophoron. Villin then appears in the proximal metanephric tubules and later increases and concentrates in the brush border of the renal proximal tubular epithelial cells. Thus villin expression can be considered as an early marker of the endodermal cell lineage during the development of the digestive system. Conversely, during the development of the excretory and genital system, villin is only expressed after the mesenchyme/epithelium conversion following the appearance of tubular structures. These observations emphasize the multiple levels of regulation of villin gene activity that occur during mouse embryogenesis and account for the strict pattern of tissue-specific expression observed in adults. In the future, regulatory elements of the villin gene may be used to target the early expression of oncogenes to the digestive and urogenital tracts of transgenic mice. PMID- 1425353 TI - Ectopic sensory neurons in mutant cockroaches compete with normal cells for central targets. AB - The cercus of the first instar cockroach, Periplaneta americana, bears two filiform hairs, lateral (L) and medial (M), each of which is innervated by a single sensory neuron. These project into the terminal ganglion of the CNS where they make synaptic connections with a number of ascending interneurons. We have discovered mutant animals that have more hairs on the cercus; the most typical phenotype, called "Space Invader" (SI), has an extra filiform hair in a proximo lateral position on one of the cerci. The afferent neuron of this supernumerary hair (SIN) "invades the space" occupied by L in the CNS and makes similar synaptic connections to giant interneurons (GIs). SIN and L compete for these synaptic targets: the size of the L EPSP in a target interneuron GI3 is significantly reduced in the presence of SIN. Morphometric analysis of the L afferent in the presence or absence of SIN shows no anatomical concomitant of competition. Ablation of L afferent allows SIN to increase the size of its synaptic input to GI3. Less frequently in the mutant population, we find animals with a supernumerary medical (SuM) sensillum. Its afferent projects to the same neuropilar region as the M afferent, makes the same set of synaptic connections to GIs, and competes with M for these synaptic targets. The study of these competitive interactions between identified afferents and identified target interneurons reveals some of the dynamic processes that go on in normal development to shape the nervous system. PMID- 1425354 TI - Developmental regulation of chromatin composition during mouse embryogenesis: somatic histone H1 is first detectable at the 4-cell stage. AB - We have examined the distribution of histone H1 in oocytes and preimplantation embryos of the mouse, using a polyclonal antibody raised against the histone H1 subtypes present in somatic cells. Immunofluorescence and immunoblotting analyses failed to detect somatic histone H1 in germinal vesicle (GV)-stage oocytes. In contrast, somatic histone H1 was detectable by immunofluorescence in the nuclei of GV oocytes previously injected with histone H1 as well as the nuclei of ovarian granulosa cells, and by immunoblotting in 8-cell embryos. 1- and 2-cell embryos examined by immunofluorescence did not contain detectable somatic histone H1. At the early 4-cell stage (54-56 hours post-hCG), 5 of 52 embryos contained somatic histone H1 in one or more nuclei. By the late 4-cell stage (66-68 hours post-hCG), however, 58 of 62 embryos contained somatic histone H1. In 8-cell embryos, morulae and blastocysts, all nuclei contained somatic histone H1 in every case. When embryos were exposed to the transcriptional inhibitor, alpha amanitin, beginning at the late 2-cell stage, they cleaved to the 4-cell stage but fewer than 10% developed histone H1 immunoreactivity. When treatment began at the early 4-cell stage, the embryos that remained at the 4-cell stage in the presence of the drug developed histone H1 immunoreactivity in half of the cases. Embryos that reached the 5- to 8-cell stage in the presence of the drug developed histone H1 immunoreactivity in every case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425355 TI - orthodenticle activity is required for the development of medial structures in the larval and adult epidermis of Drosophila. AB - Lethal alleles of orthodenticle (= otd) cause abnormalities in the embryonic head that reflect an early role in anterior pattern formation. In addition, otd activity is required for the development of the larval and adult epidermis. Clonal analysis of both viable and lethal alleles shows that the adult requirement for otd is restricted to medial regions of certain discs. When otd activity is reduced or removed, some medial precursor cells produce bristles and cuticle characteristic of more lateral structures. Similar medial defects are observed in the larval epidermis of embryos homozygous for lethal otd alleles. Antibodies to otd recognize a nuclear protein found at high levels in the medial region of the eye antennal discs, the leg discs, the genital discs and along the ventral midline of the ventral epidermis of the embryo. These results suggest that the otd gene product is required to specify medial cell fates in both the larval and adult epidermis. PMID- 1425356 TI - Platelet derived growth factor (PDGF) stimulates development of bovine embryos during the fourth cell cycle. AB - In vitro produced, 2-cell bovine embryos were cultured in serum-free medium supplemented with various combinations of growth factors to test the hypothesis that these polypeptide factors are able to signal preimplantation development. The developmental arrest that occurs during the 8-cell stage with typical culture methods might be relieved by a growth factor-dependent mechanism that would stimulate expression of the embryonic genome, thereby mimicking events that occur in vivo in the oviduct during the fourth cell cycle (8- to 16-cell stage). Subsequently, other growth factors might promote compaction and blastulation, processes which normally occur in the uterus. The effects of growth factors on early embryos were evaluated using phase contrast microscopy to monitor progression to the 8-cell stage, completion and duration of the fourth cell cycle, and blastocyst formation. Platelet derived growth factor (PDGF) promoted development beyond the 16-cell stage in 39.1% of the 2-cell embryos examined in all experiments. The duration of the fourth cell cycle among these embryos was approximately 26 hours. During development after the 16-cell stage, PDGF reduced the proportion of embryos bastulating from 12.7% to 5.8%; in contrast, transforming growth factor alpha (TGF alpha), acting during the same developmental time period, increased the proportion of embryos blastulating from 8.6% to 40.6%. These results, using serum-free medium, indicated that PDGF signalled completion of the fourth cell cycle. TGF alpha, and perhaps basic fibroblast growth factor (bFGF), promoted blastulation of 16-cell embryos during subsequent culture. PMID- 1425357 TI - Differential expression of gap junction mRNAs and proteins in the developing murine kidney and in experimentally induced nephric mesenchymes. AB - The expression of three gap junction (GJ) proteins, alpha 1 (Cx43), beta 1 (Cx32), and beta 2 (Cx26), and their transcripts were examined during the ontogeny of the mouse and rat kidney. These proteins were expressed in two non overlapping patterns. The alpha 1 GJ protein was first observed in mesenchymal cells in the 12-day mouse kidney. By day 14 and thereafter, the alpha 1 protein was detected in the transient S-shaped bodies, but not in the podocytes of the maturing glomeruli. After birth the antigen was retained in a small subset of secretory tubules. The beta 1 and beta 2 GJ proteins were similar in their developmental patterns. They were first detected in a small subset of secretory tubules in the subcortical zone of day 17 embryos. These tubules were identified by immunohistochemical markers to be proximal. At birth, practically all proximal tubules expressed the two antigens. This analysis of GJ proteins was consistent with the results of S1 nuclease protection assays showing that, while the alpha 1 mRNA appeared early during kidney development and declined around birth, the two beta mRNAs appeared later and became intensified during the last days of intrauterine development. In experimentally induced metanephric mesenchymes, a transient expression of the alpha 1 GJ protein was seen during the segregation of the tubular anlagen. beta 1 and beta 2 GJ proteins were not detected in such induced mesenchymes cultivated up to 7 days. These observations provide evidence for the cell-specific utilization of different GJ genes during different stages of kidney organogenesis. The alpha 1 gene is activated during the early segregation of the secretory tubule and might contribute to its compartmentalization, while the beta 1 and beta 2 gene products are not detected until advanced stages of development. The latter gene products might be correlated with the physiological activity of the proximal tubules in vivo, as they are not expressed in experimentally induced tubules detectable with markers for proximal tubules. PMID- 1425358 TI - The torpedo (DER) receptor tyrosine kinase is required at multiple times during Drosophila embryogenesis. AB - The torpedo (DER) gene of Drosophila, which encodes a receptor tyrosine kinase of the EGF receptor subfamily, is essential for oogenesis, embryogenesis and imaginal disc development. To gain insight into the nature of the signals transduced by the torpedo product, we have characterized the gene's loss-of function phenotype in the embryo. Through the induction of germline clones, we provide a genetic demonstration that maternal torpedo product does not contribute to zygotic development. Thus, the embryonic lethal phenotypes examined accurately reflect the consequences of eliminating all gene activity from the zygote. Temperature-shift experiments with the conditional allele topIF26 show that torpedo is required at two distinct times during embryonic development: the gene is first needed for germband retraction and for the production of anterior, posterior and ventral cuticle, then later for the secretion of ventral denticles. Since denticle formation can be severely disrupted in topIF26 animals without affecting cuticle production, the early and late requirements for torpedo appear to be functionally unrelated. torpedo, therefore, is required at multiple times in the development of the ventral epidermis, and may transduce qualitatively different signals. Since the early requirement for torpedo correlates with the first visible defect in embryonic development, increased cell death in the amnioserosa, cephalic ectoderm and ventral epidermis, the abnormalities in cuticle production and germband shortening seen in the mutant may be secondary consequences of a primary defect in cell viability. Given that the onset of cell death in torpedo embryos is not preceded by any obvious defects in mitogenesis, the establishment of cell identities or the maintenance of gene expression, it is possible that torpedo transduces a signal necessary for cell survival per se during early embryogenesis. During late embryogenesis, torpedo may mediate the reception of a second signal which regulates ventral epidermal cell differentiation. PMID- 1425359 TI - A developmentally regulated switch in neuronal responsiveness to NCAM and N cadherin in the rat hippocampus. AB - Monolayers of control 3T3 fibroblasts and 3T3 cells expressing transfected NCAM or N-cadherin have been used as a culture substratum for rat hippocampal neurons. Both NCAM and N-cadherin are expressed in the hippocampus through embryonic day 17 (E17) to postnatal day 4 (PND4); however, whereas E17 neurons responded to transfected NCAM by extending considerably longer neurites, PND4 neurons responded very poorly. The converse was true for responsiveness to N-cadherin. These data demonstrate a switch in neuronal responsiveness to NCAM and N-cadherin in the developing hippocampus. NCAM-dependent neurite outgrowth from E17 neurons was largely dependent on the presence of alpha 2-8-linked polysialic acid (PSA) on neuronal NCAM. NCAM-dependent neurite outgrowth could be fully inhibited by pertussis toxin or a combination of L- and N-type calcium channel antagonists thus providing direct evidence concerning the nature of the second messenger pathway activated in primary neurons by cell adhesion molecules (CAMs). PMID- 1425360 TI - Use of the accelerating rotarod for assessment of motor performance decrement induced by potential anticonvulsant compounds in nerve agent poisoning. AB - The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepam, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. All compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (mumol/kg) values and peak effect times were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepam, 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock [MES] and subcutaneous pentylenetetrazol [scMET]). The results suggest that at anticonvulsant doses against nerve agents, all the benzodiazepines and phenobarbital have the potential to cause a performance decrement, whereas candidate anticonvulsants of the non-benzodiazepine or non-barbiturate type would not be expected to demonstrate this effect on motor performance. It is concluded that compounds such as acetazolamide, amitriptyline and scopolamine offer alternatives to the highly decrementing benzodiazepines and phenobarbital and should be further tested as anticonvulsant candidates against nerve agent intoxication. PMID- 1425362 TI - Altered activity of hepatic mixed function oxidase, cytochrome P-450 and glutathione-S-transferase by styrene in rat fetal liver. AB - The effect of in utero exposure to styrene 200 or 400 mg/kg/day orally was studied on mixed function oxidase activities, cytochrome P-450 and glutathione contents and on the glutathione-S-transferase activity in rat fetal liver. Activities of aminopyrene-N-demethylase, aniline hydroxylase, aryl hydrocarbon hydroxylase and the cytochrome P-450 contents were significantly decreased in the fetal liver. A significant decrease in the glutathione contents and the glutathione-S-transferase activity was also observed in the liver of the fetuses of styrene exposed animals. The current data show that prenatal exposure to styrene could adversely affect the developing biotransformation process. PMID- 1425361 TI - Ninety-day toxicity study of chloral hydrate in the Sprague-Dawley rat. AB - Male and female Sprague-Dawley rats were administered drinking water containing 300, 600, 1200, or 2400 mg/L chloral hydrate for 90 days. A control group received distilled water only. No animals died during the study and no differences were observed in body weight gain or food and water consumption, except for males at the highest-dose level. Minor treatment-related effects were observed for organ weights and hematological parameters and these did not appear to be of toxicological significance. Some indications of toxicity were evident in the 2400 mg/L male group (equivalent to 168 mg/kg-day) including a significant decrease in food and water consumption and in weight gain. In addition, histopathological examination of these animals revealed an apparent increase in the incidence of focal hepatocellular necrosis. Increases in AST, ALT, and LDH, which occurred at several dose levels in males, but particularly at 200 mg/L, are consistent with the hepatocellular necrosis of minimal to mild severity diagnosed by microscopic examination. These liver changes, except for sporadic enzyme changes, were not seen in the female rats which actually consumed higher doses of chloral hydrate (e.g., 288 mg/kg-day at 2400 mg/L). On the basis of the mild liver toxicity (histopathological and clinical) observed in males at the highest doses (168 mg/kg-day), the no observed adverse effect level (NOAEL) for oral exposure of rats to chloral hydrate for 90 days is considered to be 96 mg/kg-day (600 mg/L). PMID- 1425363 TI - 2,4-Dichlorophenoxyacetic acid action on in vitro protein synthesis and its relation to polyamines. AB - The effect of 2,4-dichlorophenoxyacetic acid (2,4-D) on the in vitro synthesis of proteins was studied in Chinese hamster ovary cells. A remarkable inhibition of the synthesis of proteins was observed when cells grew for 24 h in presence of 1 mM 2,4-D. This effect was reversed by adding 0.1 mM of the three polyamines (putrescine, spermidine and spermine) to the cultured cells. The mRNA is not altered, indicating that the 2,4-D action is located at a different locus, which may be the ribosomes. From these studies, one can speculate that the alterations in the protein synthesis may be a consequence of the effect of 2,4-D on the polyamine metabolism. PMID- 1425364 TI - Effect of preperfusion of lead and aminophylline on digoxin cardiotoxicity. AB - An attempt has been made to investigate the cardiotoxicity of an interaction of Lead acetate (LA), Aminophylline (APH) and Digoxin (DGN), employing an isolated frog heart preparation. While DGN-Cardiotoxicity was potentiated by LA preperfusion, it was antagonized by APH-preperfusion as revealed by data reflecting the mean DGN perfusion time (Sec) and mean DGN exposure (microgram/10 mg heart weight) for cardiac arrest. In an experimental group involving interaction of LA, DGN and APH, preperfusion of APH has significantly diminished but not fully abolished LA-induced potentiation of DGN-cardiotoxicity. On the other hand, perfusion of APH after LA resulted not only in annulment of LA induced potentiation but also in an eventual residual protective effect of APH. It was striking that simultaneous preperfusion of APH and LA led to exacerbation of LA-induced potentiation. The results of this interaction study involving two widely prescribed cardioactive drugs, are considered to be of immense pharmaco toxicological interest. PMID- 1425365 TI - Certificates of added qualification (CAQ): a new beginning or the end? PMID- 1425366 TI - How to really use patient/client financing to get new prospects and gain commitments. PMID- 1425367 TI - Limiting the use of the quinolones--ciprofloxacin and ofloxacin. PMID- 1425368 TI - Congenital hearing loss. PMID- 1425369 TI - Craniofacial morphogenesis. PMID- 1425370 TI - Practical approach to diagnosis and management of hereditary hearing impairment (HHI). PMID- 1425372 TI - Infant hearing screening. PMID- 1425371 TI - Histopathology of deafness. PMID- 1425373 TI - Alport's syndrome. PMID- 1425374 TI - The neurofibromatoses. PMID- 1425375 TI - Communication intervention. PMID- 1425377 TI - Incidence of acoustic neuromas. AB - The annual incidence of diagnosed acoustic neuromas in Denmark during two 7-year periods from June 1976 to June 1990 was compared, collecting all operated and non operated tumors from the entire country. During the first period 278 tumors were diagnosed with an annual incidence of 38 tumors or 7.8 tumors per million per year. During the second period the annual incidence rose to 48 tumors and 9.4 tumors per million per year. There was a significant decrease of extrameatal tumor size from 33 to 26 mm and diminishing of giant tumors. PMID- 1425376 TI - Special drug communication teleconference. August 7, 1992. PMID- 1425378 TI - Otitis media and chronic middle ear effusion in the asthmatic pediatric patient. AB - In a retrospective study, a high incidence of otitis media and chronic middle ear effusion was recognized in pediatric patients with allergies, in particular, asthma. Five hundred and nineteen cases were examined to see if significant correlations could be made between asthma and 1) the development of otitis media, 2) the placement of multiple tubes, and 3) the incidence of mucoid otitis media, or "glue ear." The results of this preliminary report indicate that otitis media in the asthmatic patient seems to be a reflection of a disease affecting the entire mucociliary system in the respiratory tract and that this information should be used when making a prognosis for an asthmatic patient. PMID- 1425379 TI - Medullary hemorrhage causing vertigo and gaze nystagmus. AB - Brainstem hematomas carry a poor prognosis. There are rare reports of excellent outcome with hemorrhages in the midbrain. We report a 43-year-old woman with vertigo and minimal neurological symptoms, whose symptoms were initially mistaken for "inner ear disease," but subsequent investigations revealed a medullary hemorrhage. Recovery was complete within two weeks. While rare, medullary hemorrhage should be considered in the differential diagnosis of vertigo. PMID- 1425380 TI - The external rhinoplasty approach for rhinologic surgery. AB - The technique of external rhinoplasty has enjoyed a renaissance over the last ten years, primarily for cosmetic and functional septorhinoplasty, and we have found this to be an effective method for nasal reconstruction. Moreover, we have recognized the versatility of this approach for a variety of rhinologic problems and have utilized it for transsphenoidal hypophysectomy, sphenoidotomy, unilateral choanal atresia, septal perforation, nasal valvuloplasty and rhinophyma. We describe our technique and the rationale for employing it. We conclude that the enhanced exposure provided by the cutaneous decortication of the nose facilitates surgery of both the soft tissues and the supportive architecture of the nose. PMID- 1425381 TI - False-positive cytologic findings in Warthin's tumor: a report of two cases. AB - In two adults who smoked cigarettes, fine needle aspiration of a neck mass suggested squamous cell carcinoma. However, both lesions proved to be benign Warthin's tumor with metaplasia of the epithelial lining mimicking squamous cell carcinoma. Several clinical and histologic features can alert the physician to this finding. Awareness of the possibility of a false-positive cytologic report with Warthin's tumor is important for all physicians treating tumors of the head and neck. PMID- 1425382 TI - Head and neck manifestations of Wegener's granulomatosis. AB - Sixteen of 17 patients with Wegener's granulomatosis were found to have head and neck involvement. Rhinitis and/or nasal obstruction were the most common presenting symptoms. On initial clinical examination, paranasal sinus involvement was observed in 11 patients, ear involvement in 7 and subglottic stenosis in 2 patients. One patient presented with a large and rapidly widening ulcer on the lateral pharyngeal wall. Diagnosis was often difficult and severe delay in diagnosis occurred in 7 patients. In recent years tests for ANCA appeared to be extremely useful. PMID- 1425383 TI - Peer review--an alternative approach. PMID- 1425384 TI - Granular cell tumor of the larynx: report of two pediatric cases. AB - Granular cell tumors are uncommon neoplasms of the head and neck that usually involve the tongue. The larynx is an atypical site of involvement in adults and a rare site in children. We report two cases of subglottic granular cell tumors, one in a 10-year-old boy and the other in a 6-year-old girl. Although both were initially misdiagnosed as having asthma, radiologic, laryngoscopic, and histologic evaluation of the obstructions eventually furnished the correct diagnosis. The patients were successfully treated by surgical excision of their subglottic masses. The history, presentation, pathologic findings, management, and prognosis of this rare pediatric laryngeal tumor are explored. PMID- 1425385 TI - Selecting an oral broad-spectrum antibiotic. PMID- 1425386 TI - [Quantitative topographic characterization of the myoelectric activity distribution of the masseter muscle: mapping of spectral EMG parameters]. AB - A new method for quantitative characterization of myoelectrical masseter activity distribution by mapping of spectral EMG-parameters is described. The surface electromyograms of M. masseter were monopolarly recorded (16 channels). On the basis of registered EMG intervals (512 ms) the spectral EMG power of several frequency bands was calculated (Fast Fourier Transformation). The spectral EMG parameters between the 16 electrode positions were estimated by linear interpolation (4-nearest neighbours algorithm). Afterwards the spectral EMG parameters were fitted in a grey-tone or colour scale with 10 intervals. The so obtained EMG activity maps ("EMG-Maps") permit a quantitative-topographic characterization of myoelectrical masseter activity during different functional load procedures. The frequency range which is to consider in masseter surface-EMG investigations encloses frequencies between 15 and 500 Hz. The topography of EMG activation pattern of M. masseter is only described in a comprehensive manner when the electrode array consists of 16 electrodes and more. During defined motor tasks like clenching with controlled forces the reproducibility of EMG-Maps which respect to the topography of EMG activity pattern is very high. The absolute values of spectral EMG power as well as power changes of selected band ranges during clenching correlate to the extent of chewing forces. PMID- 1425387 TI - [Mapping spectral EMG parameters of the masseter muscle in normal probands under defined loads]. AB - In 20 healthy volunteers 16-channel surface electromyograms were monopolarly recorded from the right and left masseter muscle during defined functional conditions (force-constant bite, right and left hand side, 196, 333, 530 N chewing force, during a compensation of a load directed from a frontal or a lateral position to the mandible (20, 49, 69 N), during rest position of the mandible). The EMG curves were quantified by the calculation of spectral EMG parameters (FFT). With respect to the muscle a topographic oriented representation of the myoelectrical activity was realised by a mapping of spectral EMG-parameters. The monopolarly recorded EMG activities significantly differed between the 16 electrode positions (topographic EMG distribution pattern). During the several examination conditions of the masseter muscle different topographic distribution pattern of the myoelectrical activity were found. Moreover, the total EMG power between the muscle functions differed too. The level of the load influenced the spectral EMG power as well as, partly, the topographic EMG distribution pattern. PMID- 1425388 TI - [Computer-assisted analysis of the electromyogram for routine clinical use]. AB - A computerized EMG analysis system implemented on an MS-DOS computer was developed explicitly for clinical routine usage. It incorporates analysis of interference pattern as well as of motor unit action potentials (MUAPs). Key features of MUAP analysis are the automatic segmentation and parameterization of the EMG signal and the automatic assignment of MUAPs to motor units. Determination of muscle activity is based on threshold detection of the signal's first derivative, leading to the definition of a MUAPs central component. Its parameters (length, amplitude, maximal steepness, area between curve and base line, area between first derivative and base-line, number of turns etc.) are used when comparing MUAPs. The automatic assignment of MUAPs to motor units was implemented as an iterative procedure. MUAPs are compared to a reference MUAP and eventually assigned to it if their parameters are sufficiently similar. For such a group of MUAPs the most representative MUAP is determined which is then used as new reference MUAP in the next iteration step. Most important for clinical routine usage are simple handling, speed and the clearly arranged presentation of results. The system allows for interactive modification of MUAP assignment as well as start and end points of every MUAP. Analysis results may be displayed on the screen and printed, giving the user a quick impression of the muscle under study. Thus this method meets basic requirements for computer assisted decision making in differential diagnosis. PMID- 1425389 TI - [A comparative study of the sensory conduction velocity of the sural nerve using surface and needle electrodes]. AB - In 18 healthy persons aged 22-71 years and 17 patients suffering from clinically defined polyneuropathy the NCV of the sural nerve was measured both by antidromic technic recorded by surface electrodes and by orthodromic technique recorded by needle electrodes. Stimulation was done by bipolar surface electrodes in all cases. The skin temperature was warmed up to the minimum of 35 degrees C. The results showed in both groups a highly significant correlation of the NCV measured by antidromic and orthodromic technique. With increasing age the NCV decreased, but this was not significant. In all healthy persons sensory nerve potentials could be recorded with both techniques. In polyneuropathy missing of sensory potentials was higher in patients investigated by the antidromic technique than by orthodromic. For clinical practice measurement of NCV in sural nerve using antidromic technique should be preferred because of its simpler and faster achieving, its lower discomfort for the patient and avoiding risk of infection. However in case of missing nerve potentials, orthodromic investigation using needle electrodes for recording should be added. PMID- 1425390 TI - [Is the origin of the F-wave dependent on the magnitude of the motor unit?]. AB - It is still unknown why only few motor units (MUs) generate F-waves in response to supramaximal stimulation of a motor nerve. Therefore we investigated whether the F wave production might depend on MU-size. According to the size principle of Henneman we used the twitch force as indirect measure of MU-size. MU twitch force was determined applying the technique of intramuscular microstimulation of single motor axons. 127 MUs were analysed in 16 normal subjects. F-waves were observed in 35 MUs (27%). It was found that MUs of different sizes produced F-waves with approximately the same probability. Obviously size is not a relevant factor for the capability of a MU to produce F-waves. Only the few very large MUs of a pool may have an increased tendency to produce F-waves because four of five MUs with extremely large twitch forces (> 70 mN) generated F-waves. PMID- 1425391 TI - [Evoked potentials following cerebral ischemia in the rat: the effect of the stimulus frequency]. AB - EEG and somatosensory evoked potentials were recorded in anesthetized rats before and up to 24 h after 30 min of global forebrain ischemia. Before ischemia, SEP (sweep time 1000 ms) included primary (N25P50) components and late potentials of low amplitude. During ischemia, SEP and EEG were isoelectric. During postischemic recirculation SEP evoked by stimulation at 1.0 Hz remained severely suppressed for 24 h, although long-latency potentials (> 100 ms) recovered. Using a very low stimulation frequency of 0.1 Hz, late components strongly increased in amplitude and the overall evoked activity in the averaged post-stimulus-EEG reached 90% of control. These results demonstrate that the SEP evoked at very low stimulation frequency may serve as an early indicator of functional brain recovery after prolonged cerebro-circulatory arrest. PMID- 1425393 TI - [Automatic (computer-assisted) EEG analysis in comparison with visual EEG analysis in patients following minor cranio-cerebral trauma (a follow-up study)]. AB - The study was designed to examine the clinical applicability and use of computer assisted EEG-analysis in comparison to visual EEG-analysis in patients with minor head injuries. For this in 31 patients the following examinations were performed within the first 24 hours, one, three and eight weeks after traumatization: EEG, neurological examination and standardized evaluation of subjective complaints. The EEG was analysed visually as well as computer-assisted. The results were compared to the neurological findings and subjective complaints. Reversible posttraumatic EEG-changes were observed in 50% of all patients. The results of computer-analysis and visual analysis were equivalent in respect to baseline activity (as one of the main characteristic EEG-features). Furthermore, based on computer-assisted analysis a discriminant function is provided, which is of diagnostic and prognostic value in the single patient. We conclude that the computer-assisted EEG-analysis can be a useful alternative in EEG-routine diagnosis after minor head injuries. PMID- 1425392 TI - [Electroencephalography and cranial computed tomography in a posterior infarct]. AB - In this study we interpreted the electroencephalograms of 50 patients, all suffering from a cerebral infarction occurred in the circulation area of A. cerebri posterior with or without involvement of thalamic structures. The diagnosis was established by clinical findings and via CT-examinations. Besides the EEG-findings which always occurred in the occipital region we found alterations which exceeded the above mentioned posterior disorder of the brain function. In most cases these have been bilateral paroxysmal disorders projected into the temporal regions but lateralized to the region of the existing posterior infarction. If we had CT-examinations of cerebral infarctions in the circulation area of A. cerebri posterior without an involvement of thalamic structures, there was no projected activity which exceeded the posterior disorder in EEG. In all cases with the additional affection of thalamic structures in CT the bilateral paroxysmal EEG disorders into the temporal region were found. PMID- 1425394 TI - [Dextrose and vigilance: the effect of dextrose on the spectro-analytic parameters of pharmaco-EEG]. AB - In a randomized single-blind cross-over-design the effect of 15 g dextrose was investigated against placebo with 48 healthy subjects at two different days each. The quantitative pharmaco-EEG was recorded occipitocentral at the left side (O1 Cz) under vigilance controlled conditions and then under resting conditions (three minutes each). Having measured its baseline it was repeated six times every 20 minutes starting 10 minutes after the application of the substance. After the administration of dextrose a stabilization of vigilance could be seen in the EEG by the following differences of statistical significance (p < = 0.05) between dextrose and placebo under resting recording conditions: In the first control (14.-16. minute post) there was a significant decrease of the relative power in the delta and in the theta range combined with an increase of alpha 2. In the second control (34.-36. minute post) there was a significant decrease of relative power in the theta range and significant increase in the alpha 1 range. In the third control (54.-56. minute post) and later on no effects of dextrose were left in the pharmaco-EEG. The significant differences in the first and second control have to be interpreted as follows: After the administration of dextrose the level of vigilance was increased compared to the placebo group. PMID- 1425395 TI - Current and future trends in wound healing. AB - New adjuncts to outpatient wound care focus on diminishing infection rates and improving the speed and effectiveness of laceration repair. This article provides an overview of growth factors, proteolytic enzymes, topical antimicrobial agents, and new materials that facilitate wound closure. Also, the pathophysiology of surface wound repair is summarized. PMID- 1425396 TI - Wound evaluation and cleansing. AB - The approach to wound management in the Emergency Department does not differ from that used in evaluating other complaints. This consists of a problem-directed history and physical examination. The history should probe for host and wound factors that increase the risk of a poor outcome. The examination should emphasize a search for the involvement of underlying structures. Appropriate cleansing remains the foundation for good wound management. Until a rapid inexpensive test is available to identify wounds with low bacterial counts, the clinician should assume that all wounds have bacterial loads capable of causing infection. Therefore, most wounds should be cleansed by irrigation with at least 200 mL of normal saline. Larger quantities or 1% povidone-iodine solution may be used in wounds that have high wound or host risk factors. Wound exploration should occur in a well-lit environment and combine good hemostasis with appropriate analgesia and anesthesia. PMID- 1425397 TI - Suture materials and mechanical after care. AB - Proper wound closure necessitates a familiarity with the various types of materials and the indications and contraindications of the many techniques available. Proper wound dressing and after-care instruction ensure optimal results and help minimize complications. PMID- 1425398 TI - Sedation and analgesia. AB - The control of pain and the alleviation of anxiety are integral components in the management of soft tissue injuries in the Emergency Department. Pharmacologic agents utilized for analgesia and sedation must possess properties favorable for emergency department use. This article reviews the pharmacologic approach to patients who require sedation and/or analgesia for the management of a soft tissue injury in the Emergency Department. PMID- 1425399 TI - Local anesthetics. AB - Emergency physicians often rely on the use of local anesthetic agents to relieve patient discomfort, and research continues in an effort to develop new agents with improved anesthetic qualities. Eventually, a nontoxic, rapidly acting agent may become available that could provide profound anesthesia of long duration when applied topically to intact skin or wounds. Until the "perfect" agent is developed, physicians can help the patient by making knowledgeable choices regarding local anesthetic techniques. By choosing topical agents when appropriate and buffering agents to be infiltrated, using courteous techniques of injection, and being cognizant of potential adverse reactions, the physician can turn a potentially unpleasant and frightening situation for the patient into a positive experience that promotes satisfaction and cooperation. PMID- 1425400 TI - Emergency management of dog and cat bite wounds. AB - Most dog and cat bite injuries are minor wounds that require only local wound care as well a patient evaluation for tetanus and rabies postexposure immunoprophylaxis. For larger wounds, primary or delayed primary closure can be performed safely where indicated. When antimicrobial agents are necessary, inexpensive penicillins or cephalosporins are adequate for initial therapy. Large scale, prospective, controlled clinical studies are needed to define further the role of prophylactic antimicrobial therapy for uninfected wounds. PMID- 1425401 TI - Soft tissue infections. AB - Infections in soft tissues present with one or more of the cardinal signs of infections; however, presence of these signs may indicate manifestation of a deep systemic infection or of a noninfectious process. One of the earliest determinations to be made is whether the problem is likely to require patient admission or referral to another specialty. Only then is the primary management clear. PMID- 1425402 TI - The rational use of antimicrobial agents in simple wounds. AB - The wounds in most patients presenting to the Emergency Department will heal uneventfully and do not require the use of antimicrobial agents. Specific indications for antimicrobial use include simple wounds in patients with lymphedema, orthopedic prostheses, or in those patients prone to bacterial endocarditis. Relative indications include high-risk wounds in compromised hosts, wounds contaminated with feces, saliva, or vaginal secretions, or wounds clinically infected at the time of presentation. More important than antimicrobial administration is the commitment to aggressive, timely wound care. Pitfalls in therapy center around the injudicious use of antimicrobial agents. Such therapy does not give the physician permission to close wounds that should be left open or to give less than optimal wound care. Physicians should be keenly aware of the fact that antimicrobial use is not innocuous. The economic burden and potential for adverse side effects must be weighed against the fact that the wounds in 90% to 95% of patients presenting to the Emergency Department will heal without the use of antimicrobial agents. PMID- 1425403 TI - Detection and management of foreign bodies in soft tissue. AB - The discovery and management of foreign bodies in soft tissue are challenging problems for emergency physicians. History, physical examination, and thorough wound exploration serve as the screening test for the presence of foreign bodies. Various radiographic studies can be performed to confirm the diagnosis, to identify the object's composition and shape, and to determine its approximate location in the tissues. Once the object is discovered, the clinician must weigh the potential harm of the foreign body in its current location against the risks of attempting removal. PMID- 1425404 TI - The mangled extremity. Compartment syndrome and amputations. AB - Injuries that amputate, crush, or otherwise mangle an extremity are devastating. The possibilities of medical and psychologic disability, multiple operations, and protracted rehabilitation loom before these patients. Fortunately, expert care given by the emergency department physician maximizes the opportunity for success should the limb be replanted or revascularized. The first priority for the emergency department staff is the efficient and aggressive resuscitation of the patient. Only after this has been carried out and other life-threatening injuries addressed can attention be directed toward the injured limb. It is in the patient's best interest if the emergency department staff assumes that a mangled extremity will be replanted or revascularized. Advances in microsurgical technique and equipment have enabled surgeons to achieve salvage rates greater than 90%. Continued improvements in technique, equipment, rehabilitation, and patient selection will enable more patients to benefit from limb salvage procedures. PMID- 1425405 TI - Chronic skin ulcers. AB - Chronic skin ulceration is a common complication of diabetes, peripheral vascular disease, and disorders that decrease mobility. Local ulcer care will be successful only if the underlying cause is correctly identified and steps are taken to reverse it. This article reviews the emergency department assessment and management of the patient with chronic skin ulceration. PMID- 1425406 TI - Hyperbaric medicine for outpatient wound care. AB - After proper cleansing, debridement, and appropriate antibiotic and closure decisions, some wounds will fail to heal properly or may develop serious complications. Hyperbaric oxygen therapy offers a relatively safe noninvasive method of improving wound healing by enhancing tissue oxygenation and decreasing edema formation. Recommendation for the use of hyperbaric oxygen therapy in outpatient wound care is reviewed and the rationale behind the benefits is discussed. PMID- 1425407 TI - The development of the role of hormones in development--a double remembrance. PMID- 1425408 TI - Remembrance: growing up with the pineal gland: early recollections. PMID- 1425409 TI - FOS expression in gonadotropin-releasing hormone neurons: enhancement by steroid treatment and mating. AB - Expression of the protooncoprotein FOS is now widely believed to be a marker for neuronal activation. In female rats, a steroid-induced LH surge is accompanied by an increase in FOS-positive GnRH neurons, especially in the region of the organum vasculosum of the lamina terminalis. The present study, conducted in mice, has examined the effects of both steroid hormone treatment and sexual behavior on the expression of FOS in GnRH neurons and their distribution in the central nervous system. Thirty-three ovariectomized mice, each bearing a sc priming capsule of 17 beta-estradiol, were divided into five groups, four of which were treated sequentially with estradiol benzoate (1 microgram) and progesterone (500 micrograms). In females maintained on 17 beta-estradiol only and killed between 1400-1530 h, only 1.3 +/- 0.7% of GnRH neurons contained FOS, while treatment with estradiol benzoate/progesterone increased FOS expression significantly to 31.7 +/- 8.5% in the same time period. In animals killed at 1530-1700 h, FOS expression declined in the absence of a male (13.8 +/- 2.2%) or when the male present in the cage displayed some sexual behavior but did not ejaculate (13.0 +/ 8.6%). Interestingly, the expression of FOS was maintained at a high level (42.3 +/- 11.4%) into the late afternoon in females paired with a reproductively successful (ejaculating) male. There was a positive correlation (r2 = 0.65; P < 0.01) between the level of LH and the number of FOS-positive GnRH neurons. Hence, the expression of FOS in GnRH neurons was enhanced by both a steroid regimen leading to a LH surge and an intense level of mating behavior. Mapping of the GnRH neurons indicates that in animals with the highest level of FOS expression, FOS-positive GnRH neurons were not confined to the region of the organum vasculosum of the lamina terminalis, but were found more widely distributed along the entire rostro-caudal axis of these cells. PMID- 1425410 TI - Role of luteinizing hormone in the expression of cholesterol side-chain cleavage cytochrome P450 and 3 beta-hydroxysteroid dehydrogenase, delta 5-4 isomerase messenger ribonucleic acids in the primate corpus luteum. AB - It is well established that LH has an obligatory role in the acute production of progesterone by the primate corpus luteum in vivo because interruption of LH support to the corpus luteum at any time during the luteal phase is accompanied by an immediate and sustained fall in serum progesterone concentrations. However, recent studies have demonstrated that maximal steroidogenic capacity of cultured human luteal cells and maximal levels of messenger RNAs (mRNAs) for cholesterol side chain cleavage cytochrome P450 (P450scc) and 3 beta-hydroxysteroid dehydrogenase, delta 5-4 isomerase (3 beta-HSD) in luteal tissue are observed shortly after luteinization and decline thereafter throughout the remainder of the luteal phase. These findings would suggest that the role of LH in the acute regulation of progesterone production may differ from its role in the expression of mRNAs for steroidogenic enzymes. We initiated the current studies to define the role of LH upon the expression of mRNAs for P450scc and 3 beta-HSD by the primate corpus luteum. For this purpose, we treated cynomolgus monkeys with a potent GnRH antagonist for 1, 2, and 3 days during the luteal phase of the menstrual cycle and measured levels of mRNAs for P450scc and 3 beta-HSD in corpora lutea. Treatment of monkeys with the GnRH antagonist reduced bioactive LH concentrations to less than 5 ng/ml by 48 h of treatment, and LH concentrations remained less than 5 ng/ml thereafter. Serum progesterone concentrations were reduced by 74% after 1 day of antagonist treatment, 88% after 2 days of antagonist treatment, and by more than 95% after 3 days of GnRH antagonist treatment. Although progesterone secretion was markedly diminished after 24 h of antagonist treatment, there were no differences in mRNAs for P450scc and 3 beta HSD between antagonist-treated and control animals. However, mRNAs for P450scc and 3 beta-HSD were significantly (P < 0.05) reduced after 2 days of antagonist treatment and were nearly nondetectable after 3 days of antagonist treatment. These results demonstrate a temporal dissociation of the effects of LH on the acute regulation of progesterone secretion and the maintenance of specific mRNAs involved in progesterone production. Nonetheless, the results clearly show that LH is required for the continued expression of mRNAs for P450scc and 3 beta-HSD by the primate corpus luteum. PMID- 1425411 TI - Pituitary adenomas in mice transgenic for growth hormone-releasing hormone. AB - It has been shown that mice transgenic for human GH-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs, lactotrophs, and mammosomatotrophs, cells capable of producing both GH and PRL, by 8 months of age. We now report that GRH transgenic mice 10-24 months of age develop pituitary adenomas, which we characterized by histology, immunohistochemistry, in situ hybridization, and electron microscopy. Of 13 animals examined, all developed GH immunoreactive neoplasms that had diffuse positivity for GH mRNA by in situ hybridization. Eleven also contained PRL immunoreactivity; in situ hybridization demonstrated focal PRL mRNA in 3 of 5 immunohistochemically positive tumors. Alpha-Subunit was positive by immunohistochemistry in 8 adenomas, and TSH beta was localized in tumor cells of 5 adenomas. The adenomas had variable ultrastructural appearances, ranging from cells that resembled somatotrophs or mammosomatotrophs to cells with features of the glycoprotein hormone cell line. These findings provide conclusive evidence that protracted GRH stimulation of secretory activity can result in proliferation, hyperplasia, and adenoma of adenohypophysial cells. PMID- 1425413 TI - Progesterone control of fibronectin secretion in guinea pig endometrium. AB - Immunohistochemistry with a polyclonal antibody raised against human plasma fibronectin (Fn) was used to determine the localization of Fn in endometrial sections of guinea pig uteri isolated at the first, fourth, sixth, or tenth day of the estrous cycle. Immunoreactive Fn was constantly visualized in the endometrial stroma but absent from the epithelial layer. Fn was detected in the uterine lumen on the first or fourth day of the estrous cycle and was absent from the other sections. To determine the origin of this luminal Fn the ability of subcultured endometrial cells to produce Fn was tested, and the hormonal regulation of Fn secretion was studied. Cells were treated by estradiol alone or in association with progesterone, progesterone alone, or untreated. Whatever the hormonal treatment, stromal cells constantly secreted immunoreactive Fn into the culture medium. In the same way, the amount of Fn synthesized and basally secreted by epithelial cells was not affected by any hormonal treatments. However, Fn was found in the apical secretions of the untreated or estradiol treated epithelial cells but was undetectable in the apical compartment when the epithelial cells were treated by progesterone alone or in association with estradiol. These results indicate that Fn is constitutively secreted by stromal cells and that subcultured epithelial cells of guinea pig endometrium secrete Fn from both their basal and apical membrane domains. However, the apical secretion of Fn is specifically suppressed by progesterone. PMID- 1425412 TI - Cloning of an ovine 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid: tissue and temporal distribution of its messenger ribonucleic acid during fetal and neonatal development. AB - Glucocorticoids promote the development of many organ systems vital for extrauterine survival, and fetal cortisol provides the trigger for birth in sheep. The activity of glucocorticoids may be influenced at a cellular level by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which is responsible for the interconversion of cortisol and cortisone. To examine 11 beta-HSD gene expression during fetal development, two overlapping clones which yield a 1.4 kilobase (kb) complementary DNA encoding sheep 11 beta-HSD from a liver library were isolated by using a rat 11 beta-HSD cDNA as the probe. This cDNA contains a 879 base pair open reading frame for a protein of 292 amino acids that has more than 70% sequence identity to rat and human 11 beta-HSDs. To define the tissue distribution of 11 beta-HSD messenger RNA in sheep, selected tissues were collected from one fetus at day 130 and term (approximately 145 days), and from a nonpregnant ewe. Cellular RNA was extracted and subjected to Northern blot analysis, and a single 1.8 kb transcript was detected in the fetal and adult liver, lung, hypothalamus, anterior pituitary, and placenta. This was undetectable in adrenals and kidneys, but a smaller (1.5 kb) transcript was present in fetal and adult kidney RNA. The relative abundance of 11 beta-HSD mRNA was greatest in fetal and adult livers, and it was much higher in adult liver, lung, and kidney than in the corresponding fetal tissues. To examine whether 11 beta-HSD gene expression is developmentally regulated in the fetal sheep, liver, lung, and kidney tissues were taken from fetuses at day 60-70, day 100-110, day 125-130, at term, and from newborn lambs (24-48 h old). In the lung and kidney, the relative abundance of 11 beta-HSD mRNA did not change from day 60 to term but increased in the lungs of newborn lambs. In contrast, 11 beta-HSD mRNA levels in the liver increased between day 125 and term and rose further in the newborn. Collectively, these results demonstrate that 11 beta-HSD gene expression in sheep is regulated in a tissue-specific and developmentally programmed manner. PMID- 1425414 TI - Continuous infusion of interleukin-1 beta induces a nonthyroidal illness syndrome in the rat. AB - We studied the effects of continuous administration of recombinant human interleukin-1 beta (IL-1) on pituitary-thyroid function. Rats were equipped with minipumps loaded with either IL-1 (delivery rate, 0.5, 2.0, or 4.0 micrograms/day, ip, for 1 week) or saline. Infusion of 2.0 and 4.0 micrograms IL 1/day caused a significant decrease in plasma free T4 levels during the first 2-4 days, whereas plasma total T4 levels and T4 binding were significantly lowered throughout the week of the study. The infusion of 0.5 micrograms IL-1/day did not significantly change plasma TSH or total and free T4 levels. During the infusion of 2.0 micrograms IL-1/day, the decrease in plasma free T4 levels was paralleled by a significant decline in plasma TSH values and an impaired TSH responsiveness to TRH administration on the second day of infusion. IL-1 (2.0 micrograms/day) treatment significantly lowered plasma levels of T4-binding prealbumin, whereas it did not influence the plasma T3/T4 ratio or hepatic 5'-deiodinase activity. Plasma rT3 levels remained undetectable in both control and IL-1-treated rats. Chronic infusion of rats with 4.0 micrograms IL-1/day induced prolonged fever, whereas at the lower doses of IL-1, temperatures were elevated only on the first 2 days. IL-1 at doses of 2.0 and 4.0 micrograms/day induced a transient decrease in food intake and a suppression of body weight gain. Restriction of food consumption to the level observed in the 2.0 micrograms IL-1 experiment caused small decreases in T3, total and free T4, and TSH levels compared to those in ad libitum fed rats, but had no effects on T4 binding. We conclude that 1) continuous infusion of rats with 2.0 and 4.0 micrograms IL-1/day induces changes in thyroid economy commonly seen during infectious diseases and other systemic illnesses in rats [decreased plasma levels of TSH, T3, and (free) T4; diminished T4 binding; and decreased plasma T4-binding prealbumin levels], 2) the decrease in food intake during IL-1 treatment cannot completely explain the observed changes in thyroid hormone and TSH levels; and 3) it is highly unlikely that the decrease in thyroid hormone binding during chronic IL-1 infusion is caused by decreased food intake. Further studies are needed to clarify whether the observed alterations in thyroid economy during IL-1 infusion reflect direct effects of IL 1 per se or indirect effects caused by the mild illness induced by the cytokine. PMID- 1425415 TI - Rat somatotroph insulin-like growth factor-II (IGF-II) signaling: role of the IGF I receptor. AB - The anterior pituitary contains insulin-like growth factor-II (IGF-II) and expresses abundant IGF-II-binding sites, but the IGF-II signaling pathway in the pituitary has not been defined. We, therefore, tested the effects of recombinant human IGF-II on pituitary function by assessing the GH responsiveness of the primary rat somatotroph to IGF-II. IGF-II (3.3 nM) suppressed GH secretion by 50%, similar to the effect elicited by equimolar doses of IGF-I. In contrast, a low concentration of IGF-II (0.2 nM) did not attenuate GH secretion, while a similar IGF-I dose was sufficient to produce 50% inhibition of basal GH secretion. Fifty percent competition for [125I]IGF-I binding by IGF-I and IGF-II in GC rat pituitary cells demonstrated a 14-fold lesser affinity of the IGF-II ligand for the IGF-I receptor compared to IGF-I; therefore, the binding affinity of IGF-II for the IGF-I receptor correlates with the concentration of IGF-II required for 50% GH inhibition. Transfected GH-secreting cell lines derived from GC cells overexpressing intact human IGF-I receptors exhibited enhanced responsiveness to IGF-II. In contrast, cells transfected with a truncated IGF-I receptor cDNA lacking the cytoplasmic receptor beta-subunit (952STOP) failed to transduce the IGF-II signal, indicating that functional IGF-I receptors are required for IGF-II signaling. In addition, a mutant IGF ligand, [Leu27]IGF-II, which selectively exhibits high affinity for the type II receptor, but only minimal binding to the IGF-I receptor, did not attenuate GH secretion. However, the analog [Arg54,Arg55]IGF-II, which exhibits high affinity to the IGF-I receptor, but no binding to the type II receptor, appropriately suppressed GH secretion. This unique model of somatotroph signaling provides evidence for IGF II regulation of polypeptide hormone secretion mediated by the IGF-I receptor. PMID- 1425416 TI - Estradiol increases prolactin synthesis and prolactin messenger ribonucleic acid in selected brain regions in the hypophysectomized female rat. AB - Immunoreactive PRL which is not of pituitary origin, has been identified in many regions of the rat brain. We have previously demonstrated that estradiol increases hypothalamic immunoreactive PRL content in hypophysectomized female rats. To determine if estradiol stimulates PRL synthesis, we examined the effect of estradiol on the in vivo production of PRL, and on the expression of PRL messenger RNA (mRNA) in the hypothalamus, pons, and cerebral cortex. To examine the effect of estradiol on the in vivo production of PRL, [35S] methionine was injected into the lateral ventricle and its incorporation into immunoprecipitable PRL was determined by immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis. In estradiol, but not vehicle-treated hypophysectomized rats, a 24,000 M(r) immunoprecipitable PRL protein was detected in the hypothalamus and pons-medulla, 2 and 4 h after methionine administration. No immunoprecipitable PRL proteins were detected in the amygdala, hippocampus, cortex, or serum at either time point. In addition, in the hypothalamus, but not the pons-medulla, a second PRL band was detected with an apparent mol wt of 16,000K. To determine if estradiol increased the expression of PRL mRNA, copy DNA was obtained by reverse transcription of poly(A+) mRNA prepared from intact and vehicle or estradiol-treated hypophysectomized rats and analyzed by polymerase chain reaction amplification. In tissues from hypophysectomized rats, there was little, or no, detectable levels of PRL mRNA. In contrast, in estradiol-treated hypophysectomized rats PRL mRNA was easily detected in the hypothalamus and pons medulla by polymerase chain reaction amplification. These data suggest that estradiol increases the PRL content in the hypothalamus and pons-medulla by increasing PRL gene expression, in a manner similar to that reported in the pituitary. PMID- 1425417 TI - Interleukin-1 inhibits Leydig cell steroidogenesis primarily by decreasing 17 alpha-hydroxylase/C17-20 lyase cytochrome P450 expression. AB - Macrophage-secreted cytokines, such as interleukin-1 (IL-1), have been shown to modulate Leydig cell function. The present study examined the effect of recombinant murine IL-1 alpha on Leydig cell steroidogenesis and its mechanism of action. Addition of IL-1 to macrophage-depleted primary cultures of mouse Leydig cells caused a dose-dependent decrease in cAMP-dependent testosterone production and 17 alpha-hydroxylase/C17-20 lyase (P450c17) mRNA levels. Chronic treatment (48 h) of Leydig cells in culture with 50 microM 8-bromo-cAMP (8-Br-cAMP) resulted in a 60-fold increase in testosterone production. Treatment with 8-Br cAMP plus 0.2 and 2 U/ml IL-1 decreased testosterone production to 63 +/- 14% and 41 +/- 19%, respectively, while 5, 10, and 20 U/ml IL-1 decreased testosterone production to less than 5% that of cells treated with 8-Br-cAMP alone. Chronic treatment with IL-1 plus 8-Br-cAMP caused a shift in steroid production from testosterone to progesterone, but total steroid production (the sum of testosterone plus progesterone) was unaffected by IL-1 treatment. Treatment with 8-Br-cAMP alone caused a marked increase in P450c17 mRNA levels compared to that in control cultures, where P450c17 mRNA was undetectable. IL-1 caused a dose dependent decrease in 8-Br-cAMP-stimulated P450c17 levels (0.2 U/ml by 31 +/- 9%, 2 U/ml by 82 +/- 12%, and 10 or 20 U/ml by 100% compared to that in cells treated with 8-Br-cAMP alone). In contrast to the effect on P450c17 mRNA, only the highest concentrations of IL-1 (10 and 20 U/ml) had any effect on cholesterol side-chain cleavage enzyme (P450scc) mRNA levels (53 +/- 16% and 38 +/- 20% decreases, respectively). The inhibitory effect of IL-1 on 8-Br-cAMP-stimulated P450c17 expression was reversible. Within 12 h after the removal of IL-1, P450c17 mRNA was restored to 24%; after 24 h, to 36%; after 36 h, to 65%; and after 48 h, to 84% of that with 8-Br-cAMP alone. P450c17 expression was more sensitive to IL 1-mediated inhibition than P450scc; therefore, inhibition of P450c17 is most likely primarily responsible for the observed inhibitory effects of IL-1 on Leydig cell testosterone production. PMID- 1425418 TI - Differential capacity for cholesterol transport and processing in large and small rat luteal cells. AB - The aim of this investigation was to determine whether a specific luteal subpopulation is responsible for the hypertrophic development of the corpus luteum at midpregnancy in the rat and to determine whether there was an underlying cellular basis for the differential production of steroids by the luteal cell subtypes. To examine this, we have dispersed and separated rat luteal steroidogenic cell populations into small (< 20 microns) and large (> 30 microns) cell types by elutriation. Luteal cells were examined at early (day 3) and midpregnancy (day 14) for differences in protein content and for differential expression of proteins required for steroid production. Specific proteins examined include the P450side chain cleavage enzyme (P450scc), adrenodoxin and adrenodoxin reductase, proteins required for cholesterol conversion to progestagens in the corpus luteum, and sterol carrier protein-2 (SCP2), a protein thought to be involved in intracellular cholesterol transport. The cytochrome P450(17)alpha hydroxylase (P450(17)alpha), a key enzyme responsible for androgen biosynthesis was also examined in the isolated luteal cells. The large luteal cell population displayed an increase in total cellular protein content while the small cell type did not change with luteal development. In addition, the large luteal cells expressed proteins unique to or elevated in that cell type. Analysis by two-dimensional polyacrylamide gel electrophoresis revealed that the large cell-specific proteins had molecular masses of 23 K and 32 K and that a 14 kilodalton (kDa) protein was elevated in the large cell type relative to the small cells. The small luteal cell on day 3 of pregnancy expressed a 36 kDa protein which was barely detectable in the large cell. Immunocytochemical and Western analysis indicated that the large luteal cells contain 5.3-fold more SCP2 (P < 0.05) and 5.6-fold more P450scc (P < 0.001) relative to the small cell type. Immunocytochemical staining of adrenodoxin and adrenodoxin reductase indicate these proteins were elevated in the large cell as well. Human CG administration stimulated P450(17)alpha expression mainly in the large luteal cell population. The results of this investigation indicate, for the first time, that the large luteal cell of the rat, in contrast to the small cell type, undergoes a dramatic increase in protein content with luteal development, and that with this increase in cell size there is a concomitant increase in the large cell capacity to produce steroids. This occurs as a direct result of the enhanced expression of SCP2, P450scc, adrenodoxin and adrenodoxin reductase, proteins specifically required to transport and process cholesterol for steroid production in the large luteal cell. PMID- 1425419 TI - Hormonal and immunological characterization of the 32 kilodalton ovarian-specific protein. AB - Recent studies from this laboratory have shown that the large luteal cell of the pregnant rat contains an abundant 32 kilodalton (32K) phosphoprotein which is up regulated by estradiol. In order to assess the potential importance of this protein and to more fully understand its function, a specific polyclonal antibody was produced against the 32K and was used to examine its intraovarian localization, its tissue specificity, and its developmental regulation. Immunocytochemical localization of the 32K in the ovary of the pregnant rat found this protein to be selectively and abundantly expressed in the corpus luteum. Immunofluorescence study of small and large luteal cell populations clearly revealed an extensive localization of the 32K in the large luteal cells. Western blot analysis revealed that the 32K was absent from all steroidogenic and nonsteroidogenic tissues. Whereas this protein was absent from all other tissues examined in the rat, it was clearly expressed in corpora lutea of different animal species, including the mouse, hamster, cow, human, and pig. Although undetectable by immunohistochemistry, Western blot analysis showed this protein to be present in the follicle but at levels markedly lower than in the corpus luteum. Analysis of theca and granulosa cells revealed the presence of the 32K in both cell types. To further examine the developmental expression of this protein throughout gestation, Western blot analysis of microsomal fractions isolated from rat corpora lutea on days 3-21 of pregnancy was performed. The 32K was detected at low levels in early pregnancy, increased markedly on day 11, reached a peak on days 14-15, and remained elevated through day 21. Treatment with estradiol and PRL increased the content of the 32K in the corpus luteum. Human CG, known to cause follicular development to the preovulatory stage and to enhance luteal estradiol synthesis, also increased levels of the 32K in the corpus luteum, while it concomitantly decreased this protein in the follicle. In summary, the presence of a unique ovarian-specific 32 kilodalton protein has been established. This protein, which is present in low abundance in theca and granulosa cells, is localized to the large luteal cell and becomes abundantly expressed during midpregnancy, a time when there is a remarkable increase in luteal cell size and activity. Results of this study also demonstrate a multihormonal regulation of the 32K by tropic hormones. Thus, because of its apparent uniqueness and its timely and highly regionalized expression, the 32K may play a central role in the regulation of corpus luteum growth and function. PMID- 1425420 TI - Expression of Fos-like proteins in gonadotropin-releasing hormone neurons of Syrian hamsters: effects of estrous cycles and metabolic fuels. AB - In female mammals, reproduction is sensitive to the availability of metabolic fuels, and food deprivation has been shown to suppress pulsatile LH secretion, attenuate the preovulatory LH surge, and prevent ovulation. It has been suggested that food deprivation impairs fertility by reducing the secretion of GnRH by GnRH producing neurons in the forebrain. A series of experiments tested this hypothesis by examining the effects of estrous cycles and manipulations of metabolic fuel availability on the expression of Fos-like proteins (Fos-IR) in GnRH-immunoreactive (GnRH-IR) neurons in the forebrain of Syrian hamsters. GnRH IR neurons were detected in several areas, including the diagonal band of Broca (DBB), medial septum (MS), rostral medial preoptic area (mPOA), and caudal POA. In the more rostral regions (DBB and MS/mPOA), GnRH-IR neurons expressed Fos-IR almost exclusively on day 4 of the cycle, just after the preovulatory LH surge. However, in the caudal POA, GnRH-IR neurons expressed Fos-IR across the entire cycle, including days 1-3, when LH secretion is pulsatile. Food deprivation on days 1 and 2 of the cycle, which attenuates the LH surge and blocks ovulation in hamsters, significantly reduced the proportion of GnRH-IR neurons that expressed Fos-IR on days 2 and 4 (caudal POA) or only on day 4 (DBB and MS/mPOA). Suppression of fuel availability with insulin or 2-deoxy-D-glucose on day 1 of the cycle mimicked the effects of food deprivation and reduced the proportion of caudal POA GnRH-IR neurons that expressed Fos-IR. The results of these experiments suggest that in Syrian hamsters, there are separate populations of GnRH-IR neurons associated with pulsatile and surge modes of LH secretion. In addition, the fact that manipulations of metabolic fuel availability cause changes in the expression of Fos-IR in both populations of GnRH-IR neurons provides strong support for the hypothesis that nutritional infertility is due in part to decreased GnRH secretion. PMID- 1425421 TI - Evidence for an autocrine/paracrine role for interleukin-6 in bone resorption by giant cells from giant cell tumors of bone. AB - Interleukin-6 (IL-6) is a multifunctional cytokine whose role in osteoclastic bone resorption has not been clearly defined. Therefore, we have used giant cells, which express many features of osteoclasts, from giant cell tumors of bone as a model to examine the role that IL-6 may play in human osteoclastic bone resorption. We found that conditioned medium from 24-h cultures of highly purified giant cells (10(6)/ml) contained large amounts of IL-6 (37.9 +/- 8.8 ng/ml), similar to the amount of IL-6 produced by tumor stromal cells (29.8 +/- 11.5 ng/ml). Giant cells and stromal cells from giant cell tumors expressed IL-6 mRNA, as indicated by polymerase chain reaction analysis and in situ hybridization studies, and immunohistochemical techniques demonstrated that the giant cells expressed IL-6 receptors. The addition of a neutralizing antibody to IL-6 significantly decreased the area of dentine resorbed by purified giant cells in a dose-dependent manner, and the addition of IL-6 to cultures of purified giant cells pretreated with anti-IL-6 restored the resorbing capacity of the giant cells. These data suggest that IL-6 may act as both an autocrine and a paracrine factor for human osteoclasts and play an important role in the bone resorbing capacity of these cells. PMID- 1425422 TI - Ca(2+)-independent induction of acrosome reaction by protein kinase C in human sperm. AB - We report that activated protein kinase C (PKC) can induce acrosome reaction independently of elevated Ca2+. Addition of 12-O-tetradecanoyl phorbol-13-acetate or the membrane-permeable diacylglycerol analog 1-oleoyl-2-acetylglycerol to ejaculated human sperm resulted in stimulation of acrosomal reaction (2- to 3 fold), provided the sperm underwent capacitation. Induction of acrosome reaction by 12-O-tetradecanoyl phorbol-13-acetate was blocked by the PKC inhibitor staurosporine or by down-regulation of endogenous PKC, but not by removal of extracellular Ca2+. Acrosome reaction was also enhanced by the Ca2+ ionophore ionomycin in a Ca(2+)-dependent, PKC-independent fashion. Immunohistochemical analysis with type-specific PKC antibodies revealed the presence of PKC alpha and PKC beta II in the equatorial segment, whereas PKC beta I and PKC epsilon staining was found in the principal piece of the tail. Acrosome reaction, thus far believed to be induced only by elevated Ca2+, can therefore be triggered by activated PKC in a Ca(2+)-independent fashion. The PKC subtypes potentially involved in acrosome reaction are most likely alpha and beta II, whereas the beta I- and epsilon-subspecies might be involved in regulation of flagellar motility of human sperm. PMID- 1425423 TI - Expression of type I insulin-like growth factor receptors on human peripheral blood mononuclear cells. AB - Insulin-like growth factor-I and -II (IGF-I and IGF-II), both of which bind to type I IGF receptors, can modulate certain functions of the immune system. We, therefore, studied the expression of type I IGF receptors on purified subpopulations of peripheral blood mononuclear cells. Using two-color flow cytometry, specific binding of a monoclonal antibody directed against the type I IGF receptor (alpha IR3) was found in every subpopulation. Relatively high numbers of receptors were detected on monocytes, natural killer cells, and CD4+ T helper cells, an intermediate number of receptors on CD8+ suppressor/cytotoxic T cells, and a relatively low number of receptors on B-cells. The presence of these receptors was confirmed by specific binding of [125I] IGF-I to purified subpopulations. alpha IR3 inhibited the binding of [125I] IGF-I. The specific binding of [125I]IGF-I to monocytes could be completely inhibited by IGF-II and insulin, but higher doses of these peptides were needed than of IGF-I. Scatchard analysis revealed the presence of 734 +/- 426 receptors/monocyte, with a Kd of 0.23 +/- 0.05 nM. A lower number of receptors (230 +/- 52), but with a higher affinity (Kd = 0.05 +/- 0.02 nM), was found on purified T-cells. The positive effect of IGF-I on natural killer cell cytotoxicity indicates that the type I IGF receptors on this cell type are functional. The possibility that IGF-I mediates hormonal effects on the immune system is discussed. PMID- 1425424 TI - Set-point for parathyroid hormone release increases with postmaturational aging in the rat. AB - The plasma concentration of immunoreactive PTH (iPTH) increases with postmaturational aging in both humans and animals. In the present study we determined the basal, maximally stimulated, and maximally suppressed levels of iPTH and the concentration of whole blood ionized calcium sufficient to produce half-maximal suppression of the plasma concentration of iPTH (set-point for PTH release) in male Fischer 344 rats aged 3, 6, 12, 18, 24, and 28 months. Basal iPTH increased 2.3-fold from 3 to 28 months of age, whereas basal blood ionized calcium remained unchanged. The set-point for PTH release increased steadily and significantly (P < 0.001) from 1.19 +/- 0.09 mM at 3 months to 1.37 +/- 0.13 mM at 24 months and then declined slightly to 1.32 +/- 0.11 mM at 28 months of age. Basal iPTH correlated significantly with set-point. Neither maximally stimulated nor maximally suppressed iPTH levels showed any significant change with advancing age. These results suggest that the age-related increase in basal plasma iPTH in the rat may be in part a consequence of an increase in the set-point for PTH release. PMID- 1425425 TI - Progesterone regulation of a pregnancy-specific transcription repressor to beta casein gene promoter in mouse mammary gland. AB - Progesterone inhibits casein gene expression in the mammary gland during pregnancy. A pregnancy-specific mammary nuclear factor (PMF) is a transcriptional repressor that binds to the two separate sites of the beta-casein promoter region and mediates the inhibition of mouse beta-casein gene expression by progesterone. PMF has been detected in mouse mammary tissue during pregnancy, but not during the virginal or lactational periods. Southwestern hybridization showed that the PMF-binding sequence (TGAT/ATCA) bound a protein with a mol wt of 65 kilodaltons from mammary nuclear extract from pregnant mice, but not that from lactating animals. In this study the hormonal regulation of binding activity of PMF and its relationship to casein gene expression were also examined in vivo using ovariectomy of pregnant mice. Ovariectomy rapidly reduces the circulating progesterone and estrogen levels and induces lactogenesis in the mammary tissue of pregnant mice. After ovariectomy, the binding activity of PMF in the mammary gland was reduced to a very low level (< 5% of the sham-operated level) at 24 h, whereas the binding activity of another nuclear protein, octamer-like binding factor, was not altered 24 h after the operation. Progesterone injection at the time of ovariectomy inhibited the loss of PMF-binding activity, and the level of its activity was maintained at about 66% the level of sham-operated pregnant animals 24 h after steroid administration. The ability of progesterone to prevent the ovariectomy-mediated decrease in PMF-binding activity was specific, since other steroid hormones, such as estrogen, hydrocortisone, or testosterone, were incapable of doing so. In contrast to PMF, ovariectomy increased the level of beta-casein mRNA in mammary tissue, and this increase was inhibited by concomitant administration of progesterone, suggesting that the extent of beta casein gene expression was inversely related to PMF-binding activity in mammary tissue. These results are consistent with the view that PMF plays a role in the regulation of casein gene expression by mediating the inhibitory action of progesterone. PMID- 1425426 TI - Suramin inhibits bone resorption and reduces osteoblast number in a neonatal mouse calvarial bone resorption assay. AB - The antineoplastic properties of suramin, a polyanionic agent with demonstrated antigrowth factor activity, are under evaluation in vitro, in vivo, and in clinical trials. Suramin has been shown to have antitumor activity in patients with advanced, hormone refractory prostate cancer. During these trials, significant resolution of osseous pain was observed in nearly three quarters of the patients treated with suramin. To evaluate the effect of suramin on bone cells, we studied the effect of suramin on bone resorption in a neonatal mouse calvarial assay. Suramin inhibited bone-resorbing activity in a dose-related fashion and had an additive effect with calcitonin. Calvaria pretreated with suramin had less bone-resorbing activity, fewer attached osteoblasts, and less medium alkaline phosphatase activity than control calvaria. Suramin also inhibited osteoclastic release of tritiated proline from labeled bone in a dose dependent fashion. The effect of metastatic prostate carcinoma on bone is incompletely understood, but may be moderated by tumor-produced factors and/or cytokines. The effects of several such agents, therefore, were examined in combination with suramin. Bone resorption induced by PTH, epidermal growth factor, tumor necrosis factor, and a tumor-produced factor, PTH related-protein, was blocked by suramin. The ability of suramin to inhibit the bone-resorbing effects of several cytokines suggests that its mechanism may involve direct action on bone metabolism. Autoradiography performed on calvaria treated with labeled suramin demonstrated heavy deposition of suramin on the outer surface of the matrix, adjacent to osteoblasts and osteoclasts lining the outer table, suggesting that bone cells may be subject to high local concentrations of the drug, in keeping with this hypothesis. PMID- 1425427 TI - Posttranslational processing of proenkephalin in AtT-20 cells: evidence for cleavage at a Lys-Lys site. AB - Proteolytic processing of proenkephalin was examined in several subclones of AtT 20 cells stably transfected with rat proenkephalin cDNA (AT/PE cells). Proenkephalin is synthesized in both N-glycosylated and unglycosylated forms, as demonstrated by treatment with tunicamycin. RIAs and Western blot studies showed that AT/PE clones process proenkephalin at some, but not all, Lys-Arg sequences in a limited processing profile reminiscent of bovine adrenal chromaffin cells. Pulse-chase studies using Met5-enkephalin-Arg-Gly-Leu antiserum demonstrated that 50% of the precursor is processed within 1 h, and processing is complete after 2.5 h with the production of the 5.3-kilodalton (kDa) peptide. Further cleavage to the octapeptide Met5-enkephalin-Arg-Gly-Leu is minimal. Radiosequencing results verified the efficient cleavage of a Lys-Lys site within proenkephalin that resulted in the production of the 5.3-kDa peptide. Proenkephalin cleavage products stored within cells, which included the 5.3-kDa peptide, could be released upon stimulation of cells with BaCl2 (2-fold above basal levels), 8 bromo-cAMP or CRF (7- and 8-fold above basal levels, respectively), and a mixture of BaCl2 and 8-bromo-cAMP (20-fold above basal levels). An important difference between the processing of proenkephalin and the ACTH/endorphin precursor (POMC) in AtT-20 cells is efficient cleavage of a Lys-Lys site in proenkephalin and not in POMC. The ability of AT/PE to process proenkephalin in a natural manner makes it a suitable model system to investigate elements involved in the processing of proenkephalin at Lys-Lys sites. PMID- 1425428 TI - Interleukin-1 stimulates release of insulin-like growth factor-I from neonatal mouse calvaria by a prostaglandin synthesis-dependent mechanism. AB - Interleukin-1 alpha (IL-1 alpha) and IL-1 beta are cytokines produced by cells of the immune system and nonimmune cells, such as osteoblasts. IL-1 alpha and IL-1 beta have potent stimulatory effects on bone resorption and also have mixed effects on bone formation, suggesting that they play an important role in local regulation of bone turnover. The present study examined paracrine mechanisms underlying effects of IL-1 on bone formation. Bone formation is regulated at the local level by polypeptide growth factors such as insulin-like growth factor-I (IGF-I). IGF-I is a relatively abundant growth factor in bone matrix, is produced by osteoblasts, and stimulates osteoblastic cell proliferation and bone matrix synthesis. Recent evidence suggests that IGF-I also stimulates osteoclast formation and bone resorption. To determine whether increased or decreased IGF-I production in bone might mediate some of the effects of IL-1 on bone turnover, the effects of IL-1 alpha and IL-1 beta on IGF-I release from neonatal mouse calvaria in organ culture were examined. IL-1 alpha and IL-1 beta stimulated resorption and increased the release of IGF-I into the medium during 6 days of culture. Maximal stimulation of resorption occurred at lower concentrations of IL 1 alpha and IL-1 beta (1 pM) than were required for maximum stimulation of IGF-I release (10 pM). IL-1 beta also increased steady state levels of 7.5- and 0.9 kilobase IGF-I mRNA transcripts in total RNA extracted from cultured calvaria at 24 h. The cyclooxygenase inhibitor indomethacin (1 microM) inhibited IL-1 beta induced prostaglandin E2 (PGE2) production and inhibited resorption and release of IGF-I from calvaria. Indomethacin had a smaller effect on PTH-induced IGF-I release and had no significant effect on PTH-induced resorption. These results suggest that the effects of IL-1 on resorption and release of IGF-I may be mediated in part by a prostaglandin-dependent mechanism. Consistent with this hypothesis, PGE1 and PGE2 stimulated resorption and release of IGF-I. The dose responses for PGE2 stimulation of resorption and stimulation of IGF-I release were equivalent. The results are consistent with the hypotheses that 1) IL-1 stimulates IGF-I production by bone cells, in part by PG-dependent mechanisms; 2) the effects of IL-1 and PGs on bone formation and resorption may be mediated by locally induced secretion of IGF-I and other growth factors in bone. PMID- 1425429 TI - Ontogeny of aromatase messenger ribonucleic acid in mouse brain: fluorometrical quantitation by polymerase chain reaction. AB - A sensitive method was developed for the determination of trace amounts of aromatase mRNA in various tissues. Aromatase mRNA was quantitated by subjecting it to reverse transcription in the presence of an internal standard RNA and then amplifying the resulting cDNA by polymerase chain reaction with a fluorescent primer. The tissue distribution of aromatase mRNA in mice was examined by this polymerase chain reaction method. Results showed that aromatase mRNA is expressed in the brain, testis, and ovary, but scarcely at all in other tissues, including the placenta. In mouse brain, aromatase is mainly located in the forebrain, especially the diencephalon. In adult male and female diencephala, aromatase mRNA levels were 0.022 +/- 0.004 and 0.014 +/- 0.003 attomoles/micrograms total RNA, respectively. Aromatase in the diencephalon is known to participate in brain differentiation and sexual behavior, so changes in its mRNA levels in the brain during development were examined. Aromatase mRNA was first detected in the 12-day old fetus and was found to increase rapidly during the fetal and neonatal periods. Its mRNA levels in male and female brains reached maxima of 0.068 +/- 0.008 and 0.059 +/- 0.006 attomoles/micrograms total RNA, respectively, 3-4 days after birth and then gradually decreased to adult levels. These observations are consistent with previous data indicating that the marginal period of neonatal imprinting of sexual differences is within a week after birth and suggest that brain aromatase may be important in sexual differentiation and behavior. PMID- 1425430 TI - Potential involvement of the carboxy-terminus of the Glut 1 transporter in glucose transport. AB - The role of the carboxy-terminal domain of the Glut 1 glucose transporter was investigated using an antipeptide antibody to the C-terminal part of the molecule. The study was performed in fibroblasts transfected with the cDNA coding for the human insulin receptor. These cells acutely respond to insulin for glucose transport. Using antipeptide antibodies to Glut 1 and Glut 4, we first established that these cells expressed only Glut 1. Then, to define the role of the C-terminal part of Glut 1 in glucose transport, the antibodies were loaded into the cells by electroporation. When anti-Glut 1 immunoglobulins were introduced into the cells, a 60% increase in basal deoxyglucose and 3-O methylglucose transport was observed compared to that in cells electroporated with nonimmune immunoglobulins. The stimulatory action of the antipeptide was not due to an increase in the total amount of transporters. It was found only at low glucose concentrations, suggesting that the affinity of the transporter, rather than its maximal capacity, was changed. Finally, the effect of antibody was additive to that of insulin. The interaction between the anti-Glut 1 antibody and the carboxy-tail of the transporter seems to lead to an increase in the intrinsic activity of the transporter, suggesting that this part of the molecule could be implicated in the regulation of glucose uptake. PMID- 1425431 TI - The carboxy-terminus of parathyroid hormone is essential for hormone processing and secretion. AB - The biological function of the carboxy-terminal portion of the PTH molecule is unknown. We hypothesized that the carboxy-terminus of PTH may be essential for hormone processing and secretion. To ascertain the potential role of the carboxy terminus in transport through the secretory pathway, we constructed a series of carboxy-terminally deleted mutants of human preproPTH. PreproPTH and these truncated peptides were expressed in cell-free extracts and in acutely transfected COS 7 cells. Intact preproPTH(1-84) (115 residues) was processed to proPTH(1-84); the PTH was secreted very efficiently. In contrast, translocation across the membrane of the endoplasmic reticulum and signal sequence cleavage were mildly impaired for PTH(1-52) (83 residues), moderately impaired for PTH(1 40) (71 residues), and dramatically impaired for PTH(1-34) (65 residues). Subsequent cleavage of the prosequence and secretion from intact cells were also dramatically impaired for PTH(1-52) and undetectable for PTH(1-40) and PTH(1-34). We conclude that more than 65 residues are needed to cross the endoplasmic reticulum and that more than 83 residues are needed for efficient prosequence cleavage and secretion. Perhaps similar requirements for full transport through the secretory pathway explains why most secreted peptides are synthesized as long propeptides of at least 80 residues. PMID- 1425432 TI - Selective removal of glycosylation sites from sex hormone-binding globulin by site-directed mutagenesis. AB - Sex hormone-binding globulin (SHBG) is a homodimeric plasma glycoprotein with high affinity for sex steroid hormones. It contains two N-linked carbohydrate chains and one O-linked oligosaccharide per subunit, but their functional significance is not known. Site-directed mutagenesis of a human SHBG cDNA has enabled us to selectively disrupt the known glycosylation sites individually and in various combinations. The mutant cDNAs were expressed in Chinese hamster ovary (CHO) cells, and it was found that the presence of carbohydrates is not an absolute requirement for the secretion of SHBG from these cells, but the absence of both N-linked oligosaccharides reduced the amount of SHBG in the culture medium. In addition, the affinity and specificity of SHBG for steroid ligands was unaffected by the lack of one or more carbohydrate chains. Proportionally greater amounts (26-31%) of the mutants lacking a single N-linked carbohydrate chain failed to interact with Concanavalin-A. (Con-A) compared to normal SHBG produced by CHO cells (15%). Western analysis demonstrated that both consensus sites for N glycosylation are used and that the typical heavy [mol wt (M(r)), approximately 51,000] and light (M(r), approximately 47,000) subunit size-heterogeneity was maintained regardless of the absence of an O-linked carbohydrate at residue 7. Furthermore, the SHBG mutants containing only one N-linked oligosaccharide comprise only a single subunit with a M(r) of approximately 47,000. This suggests that the heavy subunit contains two N-linked oligosaccharides, while only one of these sites is used on the light subunit. The M(r) of the various SHBG mutants were also examined by gel filtration, and this indicated that they are all produced as homodimers and that carbohydrates are not involved in subunit association. PMID- 1425433 TI - Diminished insulinotropic effects of gastrin-releasing peptide in pregnant sheep are reproduced by progesterone treatment of nonpregnant animals. AB - Gastrin-releasing peptide (GRP) is insulinotropic in several species, but possible alterations in this action during pregnancy have not been explored. Therefore, changes in plasma insulin and glucagon concentrations were examined in response to exogenous GRP in nonpregnant and pregnant sheep that were feed restricted, fed ad libitum, or infused with glucose. Administered GRP provoked insulin and glucagon release in pregnant and nonpregnant fed animals. This effect was reduced with feed restriction and potentiated in the presence of glucose. The responses were less in pregnant than in nonpregnant animals. Interpretation of this result, however, was confounded by lower plasma immunoreactive concentrations of GRP achieved in pregnant than in nonpregnant sheep in response to the same infusion rate (picomoles per kg BW) of exogenous GRP. Therefore, nonpregnant ovariectomized sheep were treated with estradiol (E2) or E2 plus progesterone (P4), given to reproduce circulating steroid levels in pregnancy, in order to examine insulinotropic responses to GRP in the absence or presence of concurrent glucose administration. Similar plasma GRP and glucose concentrations were achieved by exogenous infusions in the different groups of nonpregnant animals treated with steroids and in control animals not receiving steroids. E2 alone did not alter the insulin response to GRP compared to control, but E2 plus P4 treatment attenuated these responses to values similar to those in pregnant animals. We conclude that GRP is insulinotropic in sheep, and this action is modulated by the circulating glucose concentration. The response to GRP is less in pregnant than in nonpregnant animals, and this attenuation is mimicked in nonpregnant animals treated with E2 plus P4. We suggest that in species such as sheep, GRP is a potentiator of glucose-stimulated insulin release. This action is diminished in response to the altered endocrine environment of pregnancy and may contribute to the metabolic changes that occur at this time. PMID- 1425434 TI - Insulin-like growth factors selectively stimulate spermatogonial, but not meiotic, deoxyribonucleic acid synthesis during rat spermatogenesis. AB - The in vitro effects of insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), truncated IGF-I, insulin, and human GH (hGH) on premitotic and premeiotic DNA synthesis of adult rat germ cells in vitro were investigated. Two-millimeter segments of seminiferous tubules from four different stages containing type A4-spermatogonia (stage I), type B spermatogonia (stage V), resting preleptotene spermatocytes (stage VIIa), and preleptotene spermatocytes in the S-phase (stage VIII-IX), respectively, were isolated by transillumination assisted microdissection. They were cultured in serum-free medium at 34 or 37 C with and without growth factors, labeled for 4 h with tritiated thymidine, and harvested at 24, 48, and 72 h. Spontaneous progression of spermatogenesis was noted at both incubation temperatures, with a more rapid rate at 37 C. IGF-I significantly stimulated [3H]thymidine uptake in originally stage I and stage V tubule segments (type A4 and B spermatogonia, respectively) after 48 h of culture at 37 C. Improved maintenance of the DNA synthesis of stage VIII-IX tubules was found after 48 h at 37 C and 72 h at 34 C. Truncated IGF-I produced a similar response, but was more potent. IGF-II showed slight stimulation of stage V tubules after 72 h at both 34 and 37 C and maintenance of stage VIII-IX tubules after 48 h at 37 C and 72 h at 34 C. hGH was effective only at 34 C, showing slight stimulation of stage I tubule segments after 48 and 72 h of incubation. Insulin at high concentrations was effective only at 37 C and stimulated DNA synthesis in stages I, V, and VIIa after 48 h and stages V and VIIa after 72 h of incubation. It is concluded that IGFs stimulate premitotic DNA synthesis of rat germ cells in vitro and may also maintain premeiotic DNA synthesis. Whether the slight response to hGH is mediated via local production of IGF-I by the tissue cultures remains to be investigated. As IGF-I and IGF-II are locally produced in the testis, the present results suggest that these factors have a selective paracrine or autocrine role in the regulation of spermatogonial proliferation during spermatogenesis. PMID- 1425435 TI - Interaction between activin and follicle-stimulating hormone-suppressing protein/follistatin in the regulation of basal inhibin production by cultured rat granulosa cells. AB - There is evidence that FSH-suppressing protein (FSP) antagonizes the action of activin on the differentiation of rat granulosa cells by binding activin in vitro. We tested the interaction of activin and FSP in this in vitro system by examining the effects of FSP on activin dose-related stimulation of immunoreactive inhibin release by rat granulosa cells. Granulosa cells (2 x 10(5) viable cells/well) from diethylstilbestrol-treated immature rats were cultured for 48 h in McCoy's 5a serum-free medium with additives and increasing doses of bovine FSP (0-30 nM) and human recombinant activin (0-20 nM). Inhibin was measured in the medium by RIA. Activin caused a dose-related increase in basal inhibin production, which was maximal between 4-10 nM activin (ED50, 0.6 nM). With the addition of FSP, an apparent increase in the ED50 of the activin dose response curves was observed, but there were no changes in the maximum response. This pattern closely resembled that of chemical antagonism of an agonist by an agent that binds with relatively high affinity to form a biologically inactive complex. Based on this premise, apparent high affinity activin binding to FSP was determined by Scatchard analysis to have a Kd of 0.13 +/- 0.07 nM (mean +/- SD) and to occur in a 2:1 or greater FSP/activin molar ratio. These data support the proposition that the antagonistic effect of FSP on activin is due to the formation of an inactive complex. PMID- 1425436 TI - The stimulation of liver angiotensinogen by glucocorticoids depends on the type of steroid and its mode of administration. AB - Glucocorticoids are well known inducers of transcription of the liver angiotensinogen (AOG) gene. However, the doses and the conditions under which they exert this effect in vivo are not known. To investigate this question, we have implanted rats with wax pellets containing 80% corticosterone (B). These pellets increased plasma B and induced clear signs of hypercorticism. However, they did not stimulate plasma AOG, whereas acute injections of dexamethasone (DEX) had a robust effect. In additional experiments, we have determined that: 1) chronic exposure to DEX was less effective than acute DEX in stimulating the production of liver AOG in rats and AOG secretion by rat hepatoma cells; 2) at maximally effective doses, B stimulated the production of AOG by hepatoma cells less effectively than DEX; and 3) DEX had less effect on AOG secretion than on AOG messenger RNA concentration, both in vivo and in vitro. All three mechanisms may have contributed concomitantly to the absence of response of plasma AOG to mild and chronic elevations of plasma B. These results suggest that glucocorticoids are unlikely to be primary regulators of liver AOG. PMID- 1425438 TI - Insulin-like growth factor-I reverses the impairment of wound healing induced by corticosteroids in rats. AB - Corticosteroids are widely used therapeutic agents that have as a major side effect the impairment of wound healing. Two hypotheses were tested: 1) that antiinflammatory corticosteroids decrease the local insulin-like growth factor-I (IGF-I) response to injury; and 2) that locally administered IGF-I would overcome methylprednisolone-mediated suppression of healing. The IGF-I concentration was measured in fluid from wire mesh cylinder wounds in rats given saline or methylprednisolone im. Rats receiving 8 and 16 mg had decreased wound IGF-I levels of 32% and 56%, respectively, compared to the saline-injected controls. IGF-I was infused (15 micrograms/day) by osmotic minipumps into wire mesh cylinder wound chambers of methylprednisolone (8 mg)-treated rats for 7 and 14 days. Methylprednisolone decreased wound DNA to 21%, hydroxyproline to 30%, and total protein to 5% of the values found in saline-infused controls. A 14-day treatment with IGF-I completely reversed the effect of methylprednisolone and increased DNA, hydroxyproline, and total protein to 216%, 109%, and 96% of saline control values, respectively. In conclusion, corticosteroids depressed wound IGF I concentrations in rats, and an infusion of IGF-I into wound chambers reversed the corticosteroid-induced impairment of wound healing, as determined by the DNA, hydroxyproline, and total protein contents in wound chambers. PMID- 1425437 TI - Opposite effects of insulin-like growth factor-I on the formation of trabecular and cortical bone in adult female rats. AB - We have previously found that in intact adult female rats, 17 beta-estradiol (E2) stimulates trabecular bone formation, which can be detected by triple fluorochrome labeling within a few days of commencing E2 treatment. We have also observed that E2 stimulates trabecular bone formation in ovariectomised (Ovx) rats given 3-amino-1-hydroxypropylidene bisphosphonate (AHPrBP). This anabolic action of E2 is presumably mediated through the local release of growth factors, of which insulin-like growth factor-I (IGF-I) is a strong contender. To assess the role of IGF-I as mediator of the anabolic action of E2 on rat trabecular bone, we examined the effect of daily sc administration of IGF-I (200 micrograms/kg) for 17 days on trabecular bone formation at the proximal tibial metaphysis in experiments using the above two models. Intact animals received fluorochrome labels on days 1, 8, and 15 of IGF-I treatment, and Ovx animals received AHPrBP (0.3 mg/kg) on days 1, 8, and 15 and fluorochrome labels on days 8 and 15. Trabecular surfaces covered by first and second labels only (termed arrested surfaces), second and third labels only (induction surfaces), and all three labels (persisting surfaces) were assessed in intact animals; double labeled surfaces were assessed in Ovx animals. We found that IGF-I increased the longitudinal growth rate in both intact rats and Ovx animals given AHPrBP. However, to our surprise, we found that IGF-I inhibited trabecular bone formation in intact animals, reducing both arrested and persisting trabecular surfaces by approximately 50%. This was associated with a doubling of periosteal bone formation, as measured at the tibial diaphysis. In Ovx animals given AHPrBP, the AHPrBP markedly inhibited trabecular bone formation compared with that in Ovx controls, and IGF-I was without effect. We conclude that, in contrast to E2, IGF I acts to increase the length and circumference of long bones and, perhaps through reactive mechanisms such as mechanical compensation, reduces rather than stimulates trabecular bone formation. PMID- 1425439 TI - Thyroid hormone-dependent redistribution of the 55-kilodalton monomer of protein disulfide isomerase in cultured glial cells. AB - In addition to the effects of thyroid hormone that are mediated through interaction with chromatin-associated receptors, T4 modulates the activity of the cellular content of the membrane-associated protein type II iodothyronine 5' deiodinase (5'D-II) by regulating its degradation through an actin-dependent extranuclear mechanism. Under the influence of thyroid hormone, the substrate binding subunit of 5'D-II is translocated from the plasma membrane to an intracellular microfilament-associated pool. In glial cells, a 55-kilodalton (kDa) protein (glial-p55), which was shown to be identical to the 55-kDa monomer of protein disulfide isomerase (PDI) also demonstrates a similar T4-dependent association to the F-actin microfilaments. To explore the role of glial-p55 in the extranuclear effect of thyroid hormone in glial cells, the effects of thyroid hormone on the subcellular localization of glial-p55 were further examined. The current study demonstrates the presence of two pools of glial-p55. While the majority of glial-p55 is associated with endoplasmic reticulum and represents PDI, approximately 25% of glial-p55 is cytosolic in the absence of thyroid hormone. Cytosolic glial-p55 is lost from the cells after mild permeabilization with saponin, and treatment of cells with T4 causes the shift of glial-p55 from the cytosolic pool to the subcellular fractions that contain the actin cytoskeleton. Crude microsomal preparations were prepared which contain membranes, microfilaments, and other particulate cell structures. In the absence of thyroid hormone, glial cells lack an intact actin cytoskeleton, and glial-p55 is easily removed from these preparations by conditions that remove extrinsic membrane proteins like PDI, such as alkaline pH and detergent extraction. In contrast, glial-p55 is not removed from the crude microsomes prepared from thyroid hormone-replete glial cells that contain an intact actin cytoskeleton. Since previous work in our laboratory indicated that glial-p55 becomes actin associated in a thyroid-dependent manner along with the substrate-binding subunit of 5'D-II, this study suggests that the 55-kDa monomer of PDI may play a role in the thyroid hormone-dependent regulation of actin polymerization and the degradation of 5'D-II. PMID- 1425440 TI - Antipeptide polyclonal antibodies specifically recognize each human thyroid hormone receptor isoform. AB - We characterized four antipeptide polyclonal antibodies (abs) able to specifically recognize each thyroid hormone receptor (TR) isoform. The abs immunoprecipitated both the in vitro synthesized receptor and the receptor expressed in E. coli and their specificity was confirmed by competition studies and immunohistochemistry. Ab activity measured by enzyme-linked immunosorbent assay decreased after preabsorption of each ab with the immunizing peptide or the specific receptor protein expressed in E. coli. No specific activity was detectable in enzyme-linked immunosorbent assay, no nuclear staining was observed after affinity column immunoabsorption, and the specific bands obtained in Western blot analysis disappeared after preabsorption with the specific TR isoform expressed in E. coli. By immunohistochemical studies we detected coordinate expression of each receptor isoform in most tissues examined. However, in heart and muscle, the beta-isoform is expressed at a very low level compared to the alpha-isoform in spite of the significant TR beta mRNA levels previously demonstrated by Northern blot analysis. We also demonstrated a different pattern of distribution of alpha- and beta-isoforms in rat testis. In this tissue the TR alpha is significantly expressed in spermatogonia nuclei, but in spermatids the beta-isoform is predominant, and only the TR beta is detectable in mature spermatozoa. PMID- 1425441 TI - Carbohydrate moiety of follitropin receptor is not required for high affinity hormone-binding or for functional coupling between receptor and guanine nucleotide-binding protein in bovine calf testis membranes. AB - Previously, we have extensively studied FSH-receptor interactions using bovine calf testis membranes, and demonstrated that the high-affinity FSH binding to receptors and coupling of FSH receptors with guanine nucleotide-binding protein (Gs protein) in a GTP-sensitive state are important initial events in FSH action. In this study, using the same plasma membrane system, we examined the glycoprotein nature of the FSH receptor and determined the contribution of carbohydrate moieties to these functions of the FSH receptor. Our approach involved enzymic deglycosylation of FSH receptors present in calf testis plasma membranes and then removal of incompletely deglycosylated FSH receptors by lectin affinity chromatography. Following treatment of testis membranes with peptide N glycosidase, the receptor, as identified by ligand-blot analysis, had a higher electrophoretic mobility indicating a decrease in M(r) from 240-200K. Treatment of testis membranes with neuraminidase caused a reduction (to approximately 225K) in the size of the receptor consistent with desialylation. However, digestion with O-glycosidase (endo-alpha-N-acetylgalactosaminidase) did not affect the mobility of the FSH receptor. These results suggest that bovine testis FSH receptor contains predominantly N-linked oligosaccharide chains, a finding which is consistent with recent predictions that N-linked glycosylation, but not O linked glycosylation sites are present in cloned FSH receptor from rat testis. Moreover, calf testis membranes after treatment with peptide N-glycosidase F, were solubilized with Triton X-100 under optimum conditions that preserve the physical and functional coupling of FSH receptors with guanine nucleotide-binding protein, and then subjected to lectin affinity chromatography. Scatchard analysis indicated that intact and deglycosylated FSH receptors bound 125I-human FSH with similar affinities. In the presence of GTP, the binding of 125I-human FSH to intact and deglycosylated receptors decreased similarly and in a noncompetitive manner. Treatment of testis membranes with NAD plus cholera toxin, but not NAD plus pertussis toxin, eliminated the GTP effect on FSH binding to enzymic deglycosylated as well as intact receptors, suggesting that the guanine nucleotide binding protein mediating GTP regulation of FSH binding in these membranes is probably Gs protein. Our results suggest that the bovine testis FSH receptor contains predominantly N-linked oligosaccharide chains consistent with recently predicted N-linked glycosylation sites of cloned FSH receptor of rat testis. The bovine testis FSH receptor does not require N-linked carbohydrate for high-affinity hormone binding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1425442 TI - Luteal control of endometrial receptivity and its modification by progesterone antagonists. AB - The objective of this study was to determine preimplantational effects of progesterone antagonists (PA) on the cell biology of the endometrium, on corpus luteum (CL) function and on the complex interactions between these two organs. The PA onapristone (ZK 98.299) or lilopristone (ZK 98.734) was given to pseudopregnant rabbits at days 5, 6, and 7 p.hCG. Three treatment protocols were investigated: Exp I, onapristone or lilopristone treatment only; Exp II, onapristone treatment after hysterectomy at day 1 p.hCG; Exp III, onapristone treatment together with 17 beta-estradiol, which represents the ultimate luteotropic hormone in the rabbit. In Exp I, onapristone and lilopristone gave rise to endometrial regression (inhibition of epithelial proliferation and differentiation, increase of apoptosis). Simultaneous addition of 17 beta estradiol in Exp III did not alter these findings. A rapid luteolysis was found in Exp I. In Exp II and III, however, onapristone was unable to impair luteal development and function. Due to the unaffected CL in Exp III and due to the 17 beta-estradiol substitution, the endometrium was capable of starting a new transformation, which met all requirements for receptivity at day 12 p.hCG. Transfers of day 4 p.c. blastocysts from untreated donors into such delayed secretion recipient rabbits at days 12 p.hCG resulted in normal implantations and normal embryonic development. Contrary to Exp III, the missing of any luteotropic substitutions in Exp I resulted in a complete inhibition of further uterine transformation. The present findings suggest that PA can exert a direct inhibitory effect on the endometrium, which is followed by an indirect luteolytic effect via endometrial mediators. The simultaneous addition of a proper luteotropic signal to the PA protocol results in survival of CL. Furthermore, this prolongation of the CL life span can be interpreted as a functional dissociation of the endometrium from the CL. PMID- 1425443 TI - Neuropeptide-Y innervation of beta-endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis. AB - Central administration of neuropeptide-Y (NPY) inhibits pituitary LH release in ovariectomized rats and stimulates LH release in intact and ovariectomized rats pretreated with ovarian steroids. Although the precise neural mechanism of this dual effect of NPY is not known, experimental evidence suggests an underlying interaction between hypothalamic NPY and the inhibitory beta-endorphin (beta END) systems in the neuroendocrine regulation of pituitary LH release in the rat. The present study was undertaken to examine the morphological basis of the interaction between these two peptidergic systems in the hypothalamus. Sections of the mediobasal hypothalamus of colchicine-pretreated female rats were double immunostained for NPY and beta END and examined by light and electron microscopy. The light brown diaminobenzidine reaction was used to visualize beta END cells, while NPY neurons were labeled with a dark blue nickel ammonium sulfate intensified diaminobenzidine reaction. Under the light microscope, a dense network of NPY-immunoreactive axons and axon terminals was observed in close apposition with beta END-immunoreactive neurons throughout the medial basal hypothalamus. Electron microscopic examination revealed that NPY-immunoreactive boutons formed axosomatic and axo-dendritic synaptic connections with beta END cells. A majority of these synaptic membrane specializations appeared asymmetrical [corrected]. In light of the previous evidence of excitatory and inhibitory effects on LH release and the existence of direct synaptic connections between NPY and LHRH neurons in the hypothalamus, the current results imply that the dual effects of NPY on LH secretion may involve modulation of LHRH secretion, both by the direct route and indirectly through the hypothalamic beta END system. PMID- 1425444 TI - 1 alpha,25-dihydroxyvitamin D3 regulates in vivo production of the third component of complement (C3) in bone. AB - We previously reported that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] specifically stimulates production of the third component of complement (C3) by murine osteoblastic cells and marrow-derived stromal cells (ST2) in vitro. In the present study we examined tissue-specific production of C3 in vivo in vitamin D deficient mice, some of which received supplemental 1 alpha,25-(OH)2D3. Western blot analysis indicated that the C3 protein band in bone was undetectable in vitamin D-deficient mice, but became distinct 48 h after 1 alpha,25-(OH)2D3 administration. The mRNA expression of C3 in bone was also undetectable in vitamin D-deficient mice and appeared as early as 24 h after 1 alpha,25-(OH)2D3 administration. mRNA expression apparently preceded the appearance of C3 protein. In contrast, there was no significant difference in the expression of hepatic C3 mRNA among normal mice fed laboratory chow and vitamin D-deficient mice with and without 1 alpha,25-(OH)2D3 administration. The serum concentration of C3 in vitamin D-deficient mice was almost identical to that in normal mice and was unchanged after 1 alpha,25-(OH)2D3 administration. 1 alpha,25-(OH)2D3 receptor (VDR) mRNAs were detected in the kidney and intestine, whereas no appreciable mRNA expression of VDR occurred in the liver. Osteopontin mRNA was expressed in response to 1 alpha,25-(OH)2D3 in the kidney, but not in the intestine. Immunohistochemical studies showed that in normal mice, the C3 protein was located mainly in the periosteal regions of calvaria and on the surfaces of bone trabeculae in the tibial metaphyses. These results demonstrate that 1 alpha,25 (OH)2D3 tissue-specifically regulates in vivo production of C3 in bone. The production of bone C3 cannot be attributed to the presence of VDR alone, and we speculate that other tissue-specific factors are required. PMID- 1425446 TI - Vitamin E protects hypothalamic beta-endorphin neurons from estradiol neurotoxicity. AB - Estradiol valerate (EV) treatment has been shown to result in the destruction of 60% of beta-endorphin neurons in the hypothalamic arcuate nucleus. Evidence suggests that the mechanism of EV-induced neurotoxicity involves the conversion of estradiol to catechol estrogen and subsequent oxidation to free radicals in local peroxidase-positive astrocytes. In this study, we examined whether treatment with the antioxidant, vitamin E, protects beta-endorphin neurons from the neurotoxic action of estradiol. Our results demonstrate that chronic vitamin E treatment prevents the decrement in hypothalamic beta-endorphin concentrations resulting from arcuate beta-endorphin cell loss, suggesting that the latter is mediated by free radicals. Vitamin E treatment also prevented the onset of persistent vaginal cornification and polycystic ovarian condition which have been shown to result from the EV-induced hypothalamic pathology. PMID- 1425445 TI - Endothelin-1 as a luteinization inhibitor: inhibition of rat granulosa cell progesterone accumulation via selective modulation of key steroidogenic steps affecting both progesterone formation and degradation. AB - Endothelin (ET)-1, is a 21 amino acid vasoactive peptide subject to regulation by cellular oxygen tension. However, an increasing body of information now suggests that ET-1 is a multifunctional peptidergic regulator the actions of which are not limited to the vascular system. Although ET-1 has been shown to inhibit the gonadotropin-supported accumulation of progesterone by cultured granulosa cells, the precise cellular mechanism(s) involved remain unknown. It was therefore the objective of this study to examine in greater detail the effects of ET-1 on progestin economy in cultured granulosa cells from immature rats. Treatment with ET-1 was inhibitory to the FSH-supported accumulation of progesterone in a dose dependent manner, an action characterized by a median inhibitory dose of 2 x 10( 11) M and a maximal inhibitory effect of 90%. This inhibitory action of ET-1 was reversible following extensive washing and could not be accounted for by a decrease in the viable cell mass. Evaluation of the activities of progesterone forming enzymes revealed ET-1 to be a potent (P < 0.01) inhibitor of cholesterol side-chain cleavage and 3 beta-hydroxysteroid dehydrogenase (HSD)/isomerase (76.1 +/- 1.2% and 47.3 +/- 8.6% inhibition, respectively). Cellular radiolabeling with [3H]pregnenolone confirmed an ET-1-induced inhibition of the FSH-supported accumulation of radiolabeled progesterone. However, this effect was concomitant with enhancement of the accumulation of more distal metabolites, i.e. 20 alpha dihydroprogesterone, 5 alpha-pregnane-3 alpha, 20 alpha-diol, and 5 alpha pregnane-3 alpha-ol-20-one. Analysis of the FSH-supported activities of the progesterone-degrading enzymes revealed ET-1 as a potent (P < 0.05) stimulator of 20 alpha-HSD and 5 alpha-reductase (3.6 +/- 1.0 and 1.7 +/- 0.3-fold, stimulation respectively). In contrast, no significant changes were observed in 3 alpha-HSD activity. Taken together, our findings demonstrate that the ET-1 induced inhibition of gonadotropin-supported progesterone accumulation constitutes a complex phenomenon wherein ET-1 inhibits the activities of steroidogenic enzymes concerned with progesterone formation while enhancing the activities of enzymes concerned with progesterone degradation. We speculate that ET-1, possibly of intraovarian origin, acts as a luteinization-inhibitor to suppress premature luteinization at a time when continued preovulatory expression of ET-1 (in the intact but not ruptured follicle) may be contingent upon relative intrafollicular hypoxia. PMID- 1425447 TI - Reversion of thyrotoxic atrial fibrillation in hypothyroid state after radioiodine treatment. AB - Twenty patients with thyrotoxic Basedow's disease complicated by atrial fibrillation lasting more than one month despite treatment with antithyroidal drugs were treated with radioiodine supplemented with an antithyroidal drug or inorganic iodine. We classified the 20 patients on the basis of atrial fibrillation reversion into two groups, one with reversion (group I) and the other without reversion (group II). In all 12 patients in group I, T4 and T3 decreased to hypothyroid levels in 3.2 +/- 1.3 months, and one month later all patients had their sinus rhythm restored while T4 and T3 remained below normal (2.6 +/- 1.1 micrograms/dl and 77.9 +/- 34.4 ng/dl, respectively). Although T4 and T3 also decreased within 3.5 +/- 1.8 months in all 8 patients in group II, one month later, atrial fibrillation persisted while T4 and T3 (10.4 +/- 5.3 micrograms/dl and 157.7 +/- 67.5 ng/dl, respectively) rose significantly compared to those in group I (P less than 0.001 and P less than 0.01, respectively). For reversion of atrial fibrillation it is important that the onset of hypothyroidism is rapidly induced by radioiodine and that hypothyroidism continues for at least one month. PMID- 1425448 TI - Possible role of cingulate cortex in regulating sexual behavior in male rats: effects of lesions and cuts. AB - The role of the cingulate cortex in regulating male sexual behavior was studied in testosterone propionate-treated castrated male rats. Males with lesions in the anterior part of the cingulate cortex showed lower levels of mount, intromission and ejaculation activities than sham-operated control males and males with lesions in the posterior part of the cingulate cortex or the frontal cortex. In male rats in which lateral connections of the anterior cingulate cortex were bilaterally interrupted by sagittal cuts, the sexual activity was much lower than in the control rats, being comparable to that of the anterior cingulate cortex lesion group, but transection of the anterior connections by a transverse cut made in the anterior part of the anterior cingulate had no effect. These results suggest that the anterior cingulate cortex and its lateral connections are critical in regulating male sexual behavior in male rats. PMID- 1425449 TI - Regulation of androgen receptor by androgen and epidermal growth factor in a human prostatic cancer cell line, LNCaP. AB - The effects of androgen and epidermal growth factor (EGF) on cell proliferation and the expression of mRNA and protein of androgen receptor (AR) were examined in an androgen-sensitive human prostatic cancer cell line, LNCaP, by Northern and Western blot analyses. The addition of 1 nM dihydrotestosterone (DHT), at which the proliferation of the cells was most stimulated, did not change the level of AR mRNA but increased the level of AR protein by reducing the turnover rate of the AR protein. EGF also stimulated the proliferation of the cells but repressed the expression of AR mRNA and protein. This repression was found to be exerted primarily at the level of transcription. When DHT and EGF were added simultaneously to the cells, the level of AR mRNA was reduced to the same degree as was accomplished by the addition of EGF alone. On the other hand, the level of AR protein increased but this increase was about 70% of that attained following the addition of DHT alone. The stimulatory effects of EGF and DHT on cell proliferation were found to be additive. These results indicate that EGF down regulates the level of AR mRNA and thereby also that of AR protein irrespective of the presence of DHT, and that EGF stimulates the proliferation of LNCaP cells through a different pathway from that of DHT. PMID- 1425450 TI - A case of hypothyroidism with simultaneous presence of stimulating type anti thyrotropin (TSH) receptor antibodies and anti-thyroxine (T4) autoantibodies. AB - We have examined a hypothyroid patient with stimulating type anti-thyrotropin (TSH) receptor antibodies and without blocking type anti-TSH receptor antibodies. Although she had high serum TSH (240 microU/ml) and low free triiodothyronine (FT3, 0.49 pg/ml) concentrations, which agree with physical findings of hypothyroidism, she had an unusually high free thyroxine (FT4) concentration (3.56 ng/dl). Incubation of her serum with 125I-T4, followed by precipitation with 12.5% polyethylene glycol (PEG) disclosed a higher binding of 125I-T4 (34.4%) than in normal controls, being 5-7%. In addition, binding of 125I-T4 to her serum gamma-globulin was completely displaced by the addition of unlabelled T4. From these results it was concluded that her serum contained anti-T4 autoantibodies. Treatment with synthetic T4 was begun and her thyroid function was monitored by sensitive TSH radioimmunoassay (RIA) and RIA of FT4 after PEG treatment. Since both sensitive TSH RIA and FT4 RIA results after PEG treatment give results concordant with the physical findings, it was concluded that both of the RIA results are useful for the evaluation of thyroid function in patients with thyroid hormone autoantibodies. PMID- 1425451 TI - A child with pituitary gigantism and precocious adrenarche: does GH and/or PRL advance the onset of adrenarche? AB - We describe a female child with pituitary gigantism and precocious adrenarche. From two years of age she showed unusual overgrowth, and at 5 years old she was 133.5 cm (+ 5.5 SD) tall and weighed 40.5 kg. Her precocious manifestations were public hair, acne vulgaris, hirsutism, and advanced bone age. Endocrinological examination revealed markedly increased serum growth hormone (GH) and prolactin (PRL), which responded paradoxically to a TRH test. In addition, the concentrations of serum dehydroepiandrosterone (DHA) and its sulfate (DHAS) were increased to adult levels, moving in accordance with changes in ACTH, which suggested that these androgens were secreted from the adrenal glands functionally. These androgens seemed to be responsible for her partial precocity. Prior reports have suggested that GH and/or PRL overproduction might have played a role in the induction of adrenarche. Also, in previous reports of 9 gigantism patients under 10 years old, the manifestation of precocious adrenarche was suggested in 8. Further investigation of the influence of GH and PRL on adrenal androgen production in children with pituitary gigantism is required. On the other hand, in short children with normal GH secretion, attention should be paid to whether or not the GH therapy in early childhood induces precocious adrenarche. PMID- 1425452 TI - Synergistic actions of cytokines and growth factors in enhancing porcine granulosa cell growth. AB - In our studies of the growth-promoting effect of a cytokine, interleukin-1 (IL 1), on cultured porcine granulosa cells, we found that the potency of IL-1 action correlated with the serum concentration in the culture medium and that IL-1 acted synergistically with insulin to increase the number of cells in the presence of low serum concentrations (0.1-1%). With granulosa cells maintained in a quiescent state under serum-free conditions, we therefore examined the effects of combined treatment with IL-1 and peptide growth factors, including insulin, on [3H]thymidine incorporation by these cells. IL-1 by itself enhanced [3H]thymidine incorporation in a concentration-dependent manner. Moreover, IL-1 acted synergistically with insulin, epidermal growth factor (EGF), or fibroblast growth factor (FGF) to enhance [3H]thymidine incorporation. Combinations of maximally effective concentrations of insulin (1 micrograms/ml), EGF (1 ng/ml), or FGF (50 ng/ml) with the maximally effective concentration of IL-1 (10 ng/ml) increased the levels of [3H]thymidine incorporation to 10-, 22-, and 20-fold, respectively, over the control values. Whereas IL-2 (0.1-100 ng/ml) did not affect [3H]thymidine incorporation, tumor necrosis factor alpha (TNF alpha) stimulated [3H]thymidine incorporation by itself and reproduced the actions of IL-1 to act synergistically with insulin, EGF, or FGF. When IL-1 and TNF alpha were added together in relatively low concentrations (1 ng/ml each), the combination had synergistic effects in enhancing [3H]thymidine incorporation. The present study demonstrates that cytokines and peptide growth factors act synergistically to markedly enhance porcine granulosa cell growth in vitro. PMID- 1425453 TI - Paracrine effect of folliculo-stellate cells on the growth factor-like action of activin A in anterior pituitary cultures. AB - Several studies have shown that pituitary folliculo-stellate (FS) cells exhibit local functions within the pituitary gland. On the other hand, we have shown previously that activin A increases the number of FSH-producing gonadotropes in cultured rat anterior pituitary cells. In this study, we investigated whether FS cells exert an influence on the action of activin A. FS cells were prepared by culturing the dispersed rat anterior pituitary cells in media containing 15% fetal calf serum and 6 mM glutamine for 15 days. Most cells had the morphological characteristics of FS cells and S-100 protein immunoreactivity, a specific marker of FS cells. The number of FSH cells, which was higher in activin A-treated than in control cultures, was reduced to the control level by incubation with activin A plus conditioned media from FS cell-enriched cultures (FSCM). This inhibitory effect of FSCM was neutralized by a follistatin antibody, but not by anti-S-100 protein or anti-basic fibroblast growth factor. Furthermore, follistatin suppressed activin A stimulated increases in the number of FSH cells in a similar inhibitory pattern to that of FSCM. Meanwhile, the number of FSH cells was not affected by FSCM or follistatin in the absence of activin A. These results suggest that FS cells are involved in the regulation of the function and/or the morphogenesis of the FSH cell-lineage by affecting the action of activin A, and that this paracrine effect of FS cells is mediated by follistatin. PMID- 1425454 TI - Inhibition by epidermal growth factor (EGF) of epidermal DNA synthesis in cultured chick embryonic skin pretreated with retinol and/or hydrocortisone: specific increment in EGF binding activity in both retinol- and hydrocortisone pretreated epidermis without correlation to EGF-mediated inhibition of cell growth. AB - When tarsometatarsal skin of 13-day-old chick embryos that had been cultured in medium containing 5% delipidized FCS with or without retinol (20 microM) and/or hydrocortisone (20 nM) for 1 day was cultured in a chemically defined medium without either the hormone or retinol for 1 day, epidermal DNA synthesis of hydrocortisone- and/or retinol-pretreated skin was inhibited when compared to that of control skin. The addition of epidermal growth factor (EGF, 10 ng/ml) to retinol- or hydrocortisone-pretreated skin further inhibited the epidermal DNA synthesis. Epidermal DNA synthesis in retinol- and hydrocortisone-pretreated skin was more strongly inhibited than in retinol- or hydrocortisone-pretreated skin, but was not further inhibited by EGF. In epidermis which was induced to differentiation toward keratinization by hydrocortisone or mucous metaplasia by retinol, EGF inhibited DNA synthesis. The extent of [125I]-EGF binding to the epidermis of retinol- and hydrocortisone-pretreated skin was 160-180% that in control skin, with no change in affinity. Hence there is no correlation between EGF-binding and the mitogenic activity of EGF. PMID- 1425455 TI - A case of autoimmune insulin antibody syndrome associated with polymyositis, empty sella and apparent high urinary output of immunoreactive insulin. AB - Patients with autoimmune insulin antibody are characterized by hypoglycemic attacks and antibodies to insulin in serum without prior insulin administration. In the present report, a patient with hypoglycemia due to autoimmune insulin antibody associated with primary empty sella syndrome and polymyositis appeared to have high urinary immunoreactive insulin (IRI) in the face of normal urinary C peptide. Consequently, the urinary IRI/C peptide ratio was apparently high. The amelioration of hypoglycemic attacks and polymyositis by prednisolone treatment was accompanied by the disappearance of the antibodies and complete normalization of the urinary IRI and IRI/C peptide ratio. No comparable rise in the urinary IRI and IRI/C peptide ratio was observed in the patients with other disorders studied. Glucose clamp and glucose tolerance study showed decreased sensitivity to exogenous or newly secreted insulin, prolonged half disappearance time of serum insulin, and normal disappearance of blood glucose. These results were consistent with the idea that autoantibodies buffered the effect of exogenous or newly secreted insulin and maintained a relatively constant level of serum free insulin which was not high enough when a large amount of glucose was loaded, but was too high after prolonged fasting, which eventually caused hypoglycemic attacks. PMID- 1425456 TI - Comparison of the incidence of association of periodic paralysis and hyperthyroidism in Japan in 1957 and 1991. AB - Periodic paralysis has been known to be associated with thyrotoxicosis in Japan. The incidence was 8.6% among male and 0.4% among female thyrotoxic patients according to a survey performed in the three major thyroid clinics in Japan in 1957. To determine the changes in the incidence during the intervening 34 years, the same type of survey was carried out again in 1991 at the same three major thyroid clinics previously involved. The incidence of paralysis in 1991 was 4.3% among male and 0.04% among female thyrotoxic patients, indicating more than a 40% decrease in the incidence. The possible cause of the decrease is related to the changes in food consumption, namely, to the fact that less carbohydrate and more potassium were taken in 1991 than in 1957. PMID- 1425457 TI - Diagnostic laparoscopy 1992: time for a new look. PMID- 1425458 TI - Indications and contraindications of diagnostic laparoscopy. PMID- 1425459 TI - Diagnostic laparoscopy in liver and biliary disease. PMID- 1425460 TI - Laparoscopy for cancer staging. PMID- 1425461 TI - Value of laparoscopy in investigating fever of unexplained origin. PMID- 1425462 TI - Diagnostic laparoscopy in focal parenchymal disease of the liver. PMID- 1425463 TI - Complications of laparoscopy. PMID- 1425464 TI - A clinical decision analysis to assess the value of laparoscopic cholecystectomy in the treatment of gallstone disease. AB - Laparoscopic cholecystectomy has been introduced for gallstone therapy and its use appears currently to be spreading very rapidly. A clinical decision analysis was performed to assess this new technique by quantitative comparison with other therapeutic modalities. A decision tree-based state transition model implemented to simulate a five-year period of follow-up was constructed. Non-surgical treatments were superior to surgical treatments in enhancing both life expectancy and quality-adjusted life expectancy on the basis of the optimal indications; one radiolucent stone < 2 cm for extracorporeal shock-wave lithotripsy and multiple floating stones for oral dissolution therapy respectively, especially in the elderly. Laparoscopic cholecystectomy was superior to open cholecystectomy in enhancing the quality of life for all eligible patients. Sensitivity analysis revealed that a higher incidence of the bile duct injury resulting from laparoscopic cholecystectomy would result in a poorer quality-adjusted life expectancy. The results of the analysis suggest the following. Nonsurgical treatments are acceptable alternatives to surgery on the basis of their optimal indications. Laparoscopic cholecystectomy has an advantage over open cholecystectomy in enhancing the patient's utility, and appears to be an attractive therapeutic modality. A proper training program is necessary to ensure the quality of this procedure in order to maintain its advantage. PMID- 1425465 TI - Evaluation of laparoscopic cholecystotomy in the treatment of gallbladder stones. AB - Laparoscopic cholecystotomy (LCT) was attempted in 34 patients with biliary type symptoms; 33 patients suffered from gallbladder stones and one patient from gallbladder polyps. In one patient the gallbladder was not accessible with the laparoscope due to extensive adhesions. In the other patients endoscopic removal of stones and polyps was possible in all cases. In the first five patients the gallbladder was drained with a Foley type catheter at the end of the procedure; in the other patients the incision of the gallbladder was closed primarily with clips and fibrin glue. At the beginning of the series two cases of complications were observed: balloon catheter deflation due to material defect and postoperative bleeding into the gallbladder; after conventional cholecystectomy the two patients made an uneventful recovery. LCT is a one-session procedure suitable for removal of symptomatic stones in well functioning gallbladders with no restrictions concerning the composition, number or size of the stones. PMID- 1425466 TI - Preliminary experience using an ultrasonic aspirator for laparoscopic cholecystectomy. AB - An ultrasonic aspirator (Olympus) specially designed for laparoscopic surgery, which also includes cautery and suction-irrigation systems, was evaluated in 40 patients undergoing laparoscopic cholecystectomy. The generating power of each system is controlled by hand or foot switches, and most operating procedures could easily be performed through a 10 mm trocar inserted through the abdominal wall. The ultrasonic aspirator successfully fragmented and aspirated soft tissue, allowing a precise differentiation between the cystic duct and artery, small vessels, lymphatics and fibrous tissue. Removal of the gallbladder could be performed successfully using the cautery and ultrasonic aspirator, whereby parts of cauterization or division could easily be identified. Identification of the cystic duct and artery, course of the cystic duct and Hartmann's pouch in the same field of vision was possible which is important for avoiding major complications such as injury of the common bile duct. No complications were seen during or after surgery in any of the patients. PMID- 1425467 TI - Management of complications of laparoscopic cholecystectomy. PMID- 1425468 TI - Comparison of open and laparoscopic cholecystectomy. PMID- 1425469 TI - Candida albicans infection complicating percutaneous endoscopic gastrostomy. PMID- 1425470 TI - The needs and wishes of outpatients undergoing upper gastrointestinal endoscopy. PMID- 1425471 TI - Apparent spontaneous regression of primary malignant lymphoma of the stomach. PMID- 1425473 TI - The effect of organic cryosolvents on actin structure: studies by small angle X ray scattering. AB - Small-angle X-ray scattering was used to probe the structure of actin in the presence of cryosolvents: 1,2-propanediol, glycerol, or a mixture of both solvents. In media devoid of polymerizing salts, a radius of gyration of 23 A is measured, as expected from the literature. In the presence of 1,2-propanediol alone, the scattering pattern begins to exhibit the characteristic slope of elongated objects with a non-negligible thickness, such as actin filaments polymerized in 40 mM KCl and 1 mM MgCl2. However, only short fragments (radius of gyration 40 A) are generated. We infer that in a medium of low ionic strength containing 15% 1,2-propanediol, actin assumes a structure closer to that of filamentous actin. 1,2-propanediol apparently induces nucleation of oligomers, as with polymerizing salts, but no propagation occurs. Glycerol and/or propanediol induce no alteration in the structure of individual salt-polymerized actin filaments. Aggregation occurs with propanediol, even in the presence of glycerol. Glycerol alone has no such effect. No shortening is detected within the scale covered, with either solvent, although 1,2-propanediol is known to shorten actin filaments. We suggest that in the absence of salts, 1,2-propanediol induces a conformational change in monomeric actin that is necessary for nucleation. This could correlate with a conformational change of actin promoters within microfilaments observed in the presence of 1,2-propanediol by other authors using different techniques. PMID- 1425472 TI - Thermal stability of bovine-brain myelin membrane. AB - The thermal behaviour of bovine-brain myelin membrane has been studied by high sensitivity differential scanning calorimetry, Fourier-transform infrared spectroscopy and thermal gel analysis. Spectroscopic results indicate that protein transitions take place between 60 degrees C and 90 degrees C, while thermal gel analysis has provided the thermal denaturation profiles of myelin proteolipid, DM-20 protein and the Wolfgram Fraction. An irreversible calorimetric transition centred at 80.3 +/- 0.2 degrees C with a specific enthalpy of 4.7 +/- 0.6 J/g of total protein has been assigned to the thermal denaturation of myelin proteolipid and DM-20 protein. The effects of the myelin storage conditions, scan rate, ionic strength and pH on this calorimetric transition have also been investigated. The thermal transition of the proteolipid practically disappears after treatment of the myelin with different amounts of chloroform-methanol 2:1 (v/v), a treatment which is generally used in proteolipid purification. On the other hand, the addition of several detergents to myelin only causes minor modifications to this transition, which then occurs at about 70 degrees C, with a specific enthalpy of between 2.5 and 3.6 J/g of total protein. These results appear to show that detergents preserve the native conformation of the proteolipid far more than do organic solvents. Hence the use of detergents would seem to be the appropriate method for proteolipid purification. PMID- 1425474 TI - Expression of a genomic clone encoding a brain potassium channel in mammalian cells using lipofection. AB - A genomic clone encoding a mouse brain K+ channel (MBK1) was isolated, characterized and expressed in COS cells using the lipofection technique. Transfected COS cells expressed voltage-dependent K+ currents that activated within 20 ms at 0 mV and showed less than 10% inactivation during 250 ms depolarizing pulses at 60 mV. Expressed K+ currents were reversibly blocked by 4 aminopyridine and tetraethylammonium, and were moderately sensitive to dendrotoxin, but insensitive to charybdotoxin. Thus MBK1, expressed transiently in a mammalian cell line, exhibits features characteristic of non-inactivating K+ channels with a conspicuous insensitivity to charybdotoxin. Lipofection is, therefore, a valuable strategy for expression of channel proteins in mammalian cells. PMID- 1425475 TI - Structure-function relationship for the highly toxic crotoxin from Crotalus durissus terrificus. AB - The three-dimensional structure of the highly toxic crotoxin from Crotalus durissus terrificus was modelled based on sequence analysis and the refined structure of calcium-free phospholipase of Crotalus atrox venom. Small-angle x ray scattering experiments were performed on aqueous solutions of crotoxin. The radial distribution function derived from these scattering experiments and the one calculated from the model structure are in good agreement. Crotoxin consists of a basic and an acidic subunit. The model strongly suggests that the overall folding motif of phospholipases has been preserved in both subunits. The basic domain has an intact active site. The residues that are expected to contact the lipid tails of the phospholipid are different from other phospholipases, but they are all hydrophobic. The acidic domain consists of three independent chains interconnected by disulfide bonds. Compared to other phospholipases the active site for the greater part has been preserved in this domain, but it is not very well shielded from solvent. Most residues normally in contact with the lipid tails of the phospholipid are missing, which might explain the acidic subunit's lack of phospholipase activity. A homology between the third chain of the acidic domain and neurophysins suggests that the acidic domain may act as a chaperone for the basic domain. PMID- 1425476 TI - Urea exchange across the human erythrocyte membrane measured using 13C NMR lineshape analysis. AB - The 13C NMR spectrum of 13C-urea in a suspension of human red cells of reduced mean cell volume was observed to contain partially resolved resonances arising from the intra- and extracellular populations of the compound. It was shown that at 25 degrees C and a magnetic field strength of 9.4 T, the rate of exchange of urea between the intra- and extracellular populations was such that the NMR lineshape was sensitive to a change in the rate of 13C-urea exchange, induced either by the addition of the urea transport inhibitor phloretin, or by the addition of 12C-urea. Total lineshape analysis of 13C NMR spectra of 13C-urea in red cell suspensions containing different concentrations of 12C-urea resulted in a weighted mean estimate for the Km and Vmax for urea equilibrium exchange from three experiments of 44 +/- 18 mM and 3.1 +/- 0.6 x 10(-8) mol cm-2 s-1, respectively (the errors denote the weighted mean standard deviations). These estimates of Km and Vmax were significantly lower than previous values reported in the literature and determined using other techniques. PMID- 1425477 TI - MNDO study of the mechanism of the inhibition of cysteine proteinases by diazomethyl ketones. AB - Diazomethyl ketones are one of the most effective irreversible inhibitors of cysteine proteinases and are therefore very important in drug design. In the present study a mechanism of inactivation is proposed based on the results of model MNDO calculations of the possible pathways. It was found that the mercaptide nucleophile, on approaching the carbonyl carbon as in the catalytic reaction path, binds to the inner diazo nitrogen. The intermediate thus formed can rearrange giving a stable product, beta-thioketone, and molecular nitrogen, with a considerable energy gain. The energy barrier to this process is equal to 36.9 kcal/mol, and corresponds to a pyramidal transition state with the vertex at the methylene carbon and the base formed by the carbonyl, thiol, and diazo groups. The energy barrier can be lowered on deprotonation of the intermediate. Based on the results obtained it was concluded that good irreversible inhibitors of cysteine proteases must fulfil two structural requirements: i) the dimensions and charge distribution must be similar to those of the peptide bond and ii) a second electrophilic center must be present in the neighbourhood of the carbonyl carbon. These are requirements which are satisfied by other strong cysteine proteinase inhibitors: beta-chloroketones and beta-ketooxiranes. PMID- 1425478 TI - The elastic deformability of closed multilayered membranes is the same as that of a bilayer membrane. AB - The elastic behavior of closed multilayered membranes is analyzed with the assumption that the constituent layers are in close contact but are unconnected in the sense that they are free to slide by one another. The system exhibits three independent elastic deformation modes for any number of the constituent layers equal to or larger than two. These are the area expansivity of the membrane neutral surface, and the local and non-local membrane bending. The corresponding elastic moduli are expressed in terms of the elastic moduli of the constituent layers, their areas, and distances between their neutral surfaces. Closed multilayered membranes only differ from a closed bilayer membrane in that for any of their shapes some of the constituent layers are expanded and some compressed. PMID- 1425479 TI - Direct spectroscopic determination of functional sulphydryl groups on intact cell surfaces by surface-enhanced resonance Raman scattering. AB - Semi-quantitative and direct determination of labelled sulphydryl groups on the surface of intact erythrocytes has been accomplished for the first time with surface-enhanced resonance Raman scattering (SERRS). The method, which involves the use of citrate-reduced silver colloids, is sensitive and selective. A 10(-8) M effective concentration of picomole quantities of sulphydryl groups was determined in the presence of the normally overwhelming signal from haemoglobin. This seminal study suggests that SERRS may be applied to other in situ, site directed labelling experiments. PMID- 1425480 TI - Investigation of the inhibition pathway of glucosamine synthase by N3-(4 methoxyfumaroyl)-L-2,3-diaminopropanoic acid by semiempirical quantum mechanical and molecular mechanics methods. AB - Glucosamine synthase (E.C. 2.6.1.16) is a promising target in antifungal drug design. It has been reported that its potent inhibitor, N3-(4-methoxyfumaroyl)-L 2,3-diaminopropanoic acid (FMDP), inactivates the enzyme by the Michael addition of the S-H group to the FMDP molecule followed by cyclisation reactions. In this study we have investigated, by means of semiempirical MNDO, PM3 and molecular mechanics methods, the energetics and kinetic possibility of the formation of various stereoisomers of the products of cyclisation of the Michael addition products detected experimentally. It was found that the substituted 1,4-thiazin-3 one can be formed in one step under alkaline conditions; the stereoisomers of this compound predicted to be the most stable on the basis of theoretical calculations are also the dominant ones in reality. PMID- 1425481 TI - Differential sensitivity of cardiac K+(ATP) channels to guanine nucleotides- evidence for a heterogeneous channel population. AB - In cell-free patches from cultured neonatal rat cardiocytes, the cytosolic presence of GTP-gamma-S (100 mumol/l) or GDP-beta-S (100 mumol/l) activated K+(ATP) channels. GTP-gamma-S required cytosolic Mg++, suggesting that an activated G-protein causes the increase in open probability. The great variations of the channel response to GTP-gamma-S and GDP-beta-S indicates that cardiac K+(ATP) channels represent a heterogeneous family. PMID- 1425482 TI - Insulin in the brain: a hormonal regulator of energy balance. PMID- 1425483 TI - Glucose toxicity. PMID- 1425484 TI - Intracellular signaling in the gonads. AB - The regulation of steroidogenesis in both the ovary and testis involves a complex interaction of a diversity of hormones and intracellular signaling pathways. The recent cloning of LH and FSH receptors has paved the way for an increased understanding of the mechanisms of receptor conformation, ligand-receptor interaction, and facilitation of post-receptor activity. The dominant role played by LH in the regulation of steroid production appears to be mediated by more than one intracellular signaling pathway. In addition to the stimulation of the adenylate cyclase-cAMP pathway, also known to be stimulated by FSH, the actions of LH may be additionally mediated by other intracellular messengers, such as those derived from the PLC pathway. Steroidogenesis in the gonads appears to be modulated by a variety of factors in addition to the gonadotropins. In this review, those factors of intracellular signaling mechanisms of which we have some understanding have been discussed. These include GnRH, PGF2 alpha, Ang II, VIP, GHRH, TNF alpha, CRF, EGF, and TGF alpha. Many of these factors have been shown to be locally synthesized, and specific receptors have been identified in the gonads. Many gonadal factors have the capacity to exert effects on steroidogenesis independent of the gonadotropins. Alternately, they have been demonstrated to alter the gonadal response to the gonadotropins via autocrine, paracrine, and intracrine mechanisms. As yet, our understanding of the intracellular signaling mechanisms used by novel gonadal regulators is limited. The involvement of the PLC, PLA2, and PLD pathways in this regard has been reviewed. It is becoming apparent that multiple signaling pathways may be stimulated by a single hormone, as in the case of GnRH, PGF2 alpha, and LH. The complexity of intracellular signal transduction in the gonads is enhanced by the potential cross-talk at numerous steps in the signaling cascades. PMID- 1425485 TI - Secretion of peptides and proteins lacking hydrophobic signal sequences: the role of adenosine triphosphate-driven membrane translocators. AB - In this review, we will emphasize the role of ATP-dependent membrane transporters in protein export and intracellular protein trafficking in prokaryotic and eukaryotic cells. ATP-binding-cassette (ABC)-transport proteins, also termed "traffic ATPases," belong to a superfamily of ubiquitous ATP-driven membrane transporters that share extensive sequence similarity and highly conserved domain organization. They are implicated in a remarkable variety of transmembrane transport processes, including the transport of ions, heavy metals, sugars, anticancer drugs, amino acids, oligopeptides, and proteins. Bacterial ABC proteins include the well-characterized periplasmic permeases involved in nutrient uptake, but also include protein secretion systems, such as the exporter for the Escherichia coli enterotoxin hemolysin A. Prominent eukaryotic members of this superfamily include the human P-glycoprotein (which is associated with the phenomenon of multiple drug resistance in tumor cells), the product of the cystic fibrosis gene (CFTR), the gene (pfmdr) implicated in chloroquine resistance of the malarial parasite, putative peptide transporters encoded at the locus for the class II major histocompatibility complex (MHC), and the yeast Ste6 transporter which mediates export of a peptide hormone that lacks a classical hydrophobic signal peptide. The well-established function of prokaryotic ABC-transporters in the secretion of proteins without typical signal sequences, and the example set by the Ste6 transporter, have led to the reasonable hypothesis that certain ABC proteins in animal cells may be operating by a similar mechanism to mediate the export of a new class of secretory proteins, those lacking a classical hydrophobic signal peptide. PMID- 1425486 TI - Interleukin-1 and beta-cell function: more than one second messenger? AB - Cytokines, in particular IL-1, released mainly by infiltrating macrophages, can be one of the key mediators of immune-induced beta-cell destruction in IDDM. IL-1 is able to induce suppression of insulin release and biosynthesis in cultured rat pancreatic islets. In addition, the cytokine shows clear cytotoxic effects leading to beta-cell death. The proposed mechanisms of action of IL-1 after binding to the beta-cell receptors are varied. Concerning the cytotoxic effects of the cytokine, the role of oxygen free radicals, mainly derived from arachidonate metabolism (see Fig. 1) is clear, and possibly potentiated by a cytosolic Na(+)-mediated alkalinization of the beta-cell exposed to the cytokine. In fact, an increased influx of Na+ may explain some of the cytotoxicity since it results in concomitant water uptake leading to swelling of the endoplasmic reticulum. NO formation also seems to be related to the cytokine-induced cytotoxicity since inhibition of the NO synthase abolishes the effects of the cytokine (see Fig. 1). In relation to the inhibitory effects of the cytokine on the beta-cell, different studies point toward almost all known second messenger systems already described for several hormones, such as cAMP formation, increased phospholipase C activity, changes in cytosolic Ca++, and altered gene transcription (see Fig. 1). Of particular interest is the protease activation associated with IL-1 (a serine protease) that seems to be clearly connected with the effects of the cytokine upon the beta-cell. In conclusion, the different studies devoted to the problem of IL-1 signal transduction on the beta-cell seem to indicate that the action of the cytokine on the pancreatic insulin-secreting cells is not associated with an individual second messenger system but rather seems to be related to a plurifactorial transduction system. PMID- 1425487 TI - Analysis of the mechanism of steroid hormone receptor-dependent gene activation in cell-free systems. PMID- 1425488 TI - Receptor-effector coupling by G proteins: implications for normal and abnormal signal transduction. PMID- 1425489 TI - The thyrotropin receptor and the regulation of thyrocyte function and growth. PMID- 1425491 TI - Merritt-Putnam: the legacy. PMID- 1425490 TI - Status epilepticus in children, adults, and the elderly. AB - Status epilepticus (SE) is a major neurological and medical emergency associated with a high morbidity and mortality. Retrospective and prospective studies from the Medical College of Virginia Epilepsy Research Center have been utilized to investigate several clinical and epidemiological factors associated with SE. Univariate and multivariate logistic regression analysis of predictive indicators in patients with SE indicated that seizure duration, certain specific etiologies, and age were predictors of mortality. Sex, race, and certain other etiologies were not found to be factors that significantly affect mortality. These findings demonstrate that specific indicators are important in predicting mortality in SE. Preliminary prospective epidemiological data from Richmond, Virginia suggested that more than 250,000 cases of SE may occur annually in the United States with a mortality greater than 55,000 individuals. Studies comparing community and university hospitals in Richmond indicate that the mortality and clinical variables associated with SE in these two hospital populations are essentially identical. Further investigations employing prospective population-based studies are essential in evaluating the epidemiology and mortality of SE. PMID- 1425492 TI - Metabolism of antiepileptic medication: newborn to elderly. AB - Epilepsy affects individuals of all ages. Regimens of antiepileptic drugs (AEDs) and side-effect profiles differ for infants, children, adults, and the elderly. Thus, the epileptologist must be familiar with the specific changes of AED metabolism with age. In general, metabolic rates are fastest in children; therefore, AED half-lives are shortest in this group. Rates of AED elimination are slowest in neonates, infants, and children. Thus, children need larger dosages, on a mg/kg basis, than adults. The usual phenytoin (PHT) dosage in adults is 4-6 mg/kg per day, but children may need a dosage three to five times higher. On the other hand, the PHT dosages in the elderly may need to be 3-4 mg/kg per day to achieve therapeutic levels. Likewise, the half-life of carbamazepine (CBZ) is shortest in children and the elderly. Profiles of metabolites may also be age-specific, a difference of particular importance for valproate (VPA). The relative amount of VPA metabolized to 4-ene is more than twofold less in adults than in children, which may explain the different profile of hepatotoxicity seen by age. The elderly may be more vulnerable to adverse effects of AEDs. Many elderly have neurologic deficits that may render them more vulnerable to neurotoxic effects such as ataxia and cognitive disturbances. Also, low serum albumin concentrations, which result in decreased binding, may mask high serum AED concentrations. The hyponatremia associated with CBZ may be a particular concern in the elderly. Gingival hyperplasia, a concern in children, may not be a problem in the elderly. PMID- 1425493 TI - Pregnancy and the risk of teratogenicity. AB - One in every 250 newborns is exposed to antiepileptic drugs (AEDs) in utero. Various studies have attributed a teratogenic effect to these AEDs, mainly consisting of major malformations, minor anomalies, intrauterine or postnatal growth failure, and psychomotor retardation. Prospective studies confirm the increased risk of major malformations. The absolute risk of 7-10% is about 3-5% higher than that in the general population. Barbiturates and phenytoin (PHT) are particularly associated with congenital heart malformations, facial clefts, and some other malformations. Valproate (VPA) and carbamazepine (CBZ) are associated predominantly with spina bifida aperta (1-2 and 0.5-1.0% risk, respectively) and hypospadias. Bilateral radial aplasia is a rare but specific effect of VPA. Several studies identified additional risk factors, i.e., high daily AED dosage, high maternal serum AED concentrations, low folate levels, or polytherapy [phenobarbital (PB) plus primidone (PRM) plus PHT or CBZ plus VPA plus PB with or without PHT]. The few prospective studies controlled for socioeconomic factors or that considered parental findings indicate that risk of specific cognitive defects rather than risk of overall mental retardation may be increased, that early growth retardation is followed by a catch-up growth to normal, and that ocular hypertelorism and nail hypoplasia are the only minor anomalies causally related to PHT exposure. However, no final conclusions can be made. Genetic predisposition to the teratogenic side effects of AEDs plays a role, codetermining the recurrence risk if the woman has previously given birth to a child with a major malformation. The molecular genetic basis of this predisposition is unclear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425494 TI - Hormones and epilepsy through the lifetime. AB - Hormones influence brain function from gestation throughout life and may affect the seizure threshold by altering neuronal excitability. Estrogen enhances and progesterone diminishes neuronal excitability experimentally, whereas testosterone and corticosteroids have less consistent effects. Hormonal effects in the CNS also depend on the region of brain in which the hormone acts. Sites of action for most steroid hormones include the hypothalamus and limbic cortex, providing a mechanism for modulating behavior and endocrine function. Seizure patterns may change at certain life stages, perhaps as a result of alterations in hormones. At puberty, epilepsy and benign rolandic epilepsy often remit, while juvenile myoclonic and photosensitive epilepsy may arise. Other types of epilepsy do not respond predictably to events in the reproductive life or to advancing age. In some women, fluctuations in hormones over the menstrual cycle appear to increase seizure vulnerability, probably reflecting changes in relative amounts of estrogen and progesterone. Seizure patterns can be altered, for better or worse, during pregnancy. Whether this reflects the effects of hormones or changes in levels of antiepileptic drugs is not resolved. More information is needed about changes in established epilepsy at menopause and in the elderly. Better understanding of endocrine effects on seizures over a lifetime should lead to more effective epilepsy therapies. PMID- 1425495 TI - Seizure disorders: the changes with age. AB - Age has a profound influence on our approach to the convulsive disorders. Age is a variable which is an important determinant for risk factors for epilepsy. Age, as a surrogate of brain maturation, is a determinant of the specific characteristics of the seizure disorder in those with epilepsy, and age-related changes in these manifestations can be identified. Age is a determinant for the occurrence of acute symptomatic seizures in several types of metabolic or central nervous system insults. Age is a determinant for prognosis, whether one considers remission, medication withdrawal in those entering remission, relapse following prolonged remission, or mortality. Last, age per se seems to be a risk factor for epilepsy independent of other factors. This seems particularly true for partial seizures. PMID- 1425496 TI - Effects of high-dose gamma-vinyl GABA (vigabatrin) administration on visual and somatosensory evoked potentials in dogs. AB - gamma-Vinyl GABA (GVG, vigabatrin) is a GABA transaminase-inhibiting antiepileptic agent. In dogs, chronic GVG administration produces reversible microvacuolation (intramyelinic edema) in discrete brain regions and slowing in central afferent transmission as measured by somatosensory evoked potentials (SEPs). Because this microvacuolation is especially prominent in the optic tract, this study tested the sensitivity of visual evoked potentials (VEPs) to GVG induced changes in conduction. We also replicated the earlier SEP findings. Eight beagles received daily oral vigabatrin at the maximum tolerated dose (300 mg/kg/day); four were placebo controls. Cortical VEPs and SEPs were recorded using scalp needle electrodes at baseline and every 2 weeks throughout treatment. One treatment dog died at 2 weeks. The remainder showed an increase in central latencies beginning at 6 weeks, attaining significance (p < 0.05) at 8 and 10 weeks for SEPs and VEPs, respectively. No changes occurred in peripheral or spinal conduction in treated dogs, or in any measure in control dogs. Three GVG and two control dogs were followed after drug was withdrawn; both VEP and SEP measures returned to baseline values within 5 weeks. These findings support the use of VEPs and SEPs to monitor patients receiving vigabatrin therapy. PMID- 1425497 TI - Treatment of pediatric epilepsies with gamma-vinyl GABA (vigabatrin). AB - Three large studies, all including more than 60 children, on the efficacy on gamma-vinyl GABA (vigabatrin, GVG) in the treatment of childhood epilepsy have been reviewed. On the basis of these and other studies, we conclude that (a) GVG is a promising drug for the treatment of childhood epilepsy, (b) GVG is effective both in partial and generalized epilepsies, (c) GVG seems to be effective in the treatment of symptomatic infantile spasms, (d) no clear dose-response relationship has been demonstrated, (e) a dose of 40-80 mg/kg/day is recommended, and (f) although tolerance is excellent, hyperactivity seems to occur more frequently in children than in adults. PMID- 1425498 TI - Gamma-vinyl GABA (vigabatrin): clinical experience in adult and adolescent patients with intractable epilepsy. AB - Clinical experience with gamma-vinyl GABA (GVG, vigabatrin) has accumulated mainly in Europe, where the drug has been licensed in several countries since 1989. Short-term efficacy studies in adolescent and adult patients with intractable drug-resistant epilepsy have shown that approximately 50% exhibit a reduction in seizure frequency of one-half or more but rarely complete seizure control. The best results are in patients with partial seizures with or without secondarily generalization. GVG responders have been followed for periods of up to 5 years, and overall 10-20% may exhibit subsequent seizure breakthrough, as probably occurs with any drug in such chronic patients. The most common side effect is drowsiness. Reversible behavior disorders, psychoses, and depression rarely occur in predisposed individuals. No new long-term side effects have been reported but vigilance is necessary. Studies of GVG as a first-line drug in newly diagnosed epileptic patients are proceeding. PMID- 1425499 TI - A special issue dedicated to the memory of I. J. Selikoff. PMID- 1425500 TI - Hidden assumptions in environmental research. AB - A major challenge in both the design of epidemiologic studies of exposure to toxic agents and the interpretation of the findings is to recognize and to accommodate the complex biologic assumptions that underlie population-based research. Environmental health research is grounded on a scientific foundation that blends toxicology with epidemiology. Toxicology without human population studies often leads to findings uninterpretable for purposes of risk assessment. Epidemiologic studies are often less helpful than they could be because the variation in response is seldom addressed, the effects under study are often small in magnitude and easily confounded, and exposure estimates are crude. The net bias is to reduce the risk estimate, perhaps substantially. Biological variation has usually been treated as "noise" in the system but it is a more basic problem that lends itself to investigation and quantification. Improved modeling of the biological determinants of response is needed if results are to be generalizable and interpretable in mechanistic terms. PMID- 1425501 TI - Environmental health in the journals. AB - The environmental health aspects of general medical practice have attracted the attention of many professional organizations in the past few years, including the American College of Physicians, the Institute of Medicine, and the American College of Occupational Medicine. To assess the degree of emphasis placed on environmental health issues in professional journals, a survey of representative specialty and general medical journals was conducted through a Medline literature search. Over the past 15-year period (1976-1990) specialty journals demonstrated a dramatic and consistent increase in published articles that were indexed under the headings environmental pollution, environmental pollutants, and environmental cancer. General medical journals also demonstrated continued increases in the rate of published articles addressing these environmental health topics. Within the environmental categories, air pollution, especially that due to dusts, was the most heavily indexed topic, followed by water pollution, especially that due to chemical contamination. This study supports the notion that environmental health issues are assuming more importance in general medical practice, especially within the specialty of occupational medicine. PMID- 1425502 TI - Challenges of worker notification in neurotoxic studies of the central nervous system. AB - Researchers who study the central nervous system (CNS) face special challenges in notifying study participants about the research results. There are human research guidelines regarding the communication of information to subjects at the outset of a CNS research study. Yet there are few guidelines on how to communicate to the subject the research findings and the interpretation of individual results at the study's conclusion. The research subjects may desire detailed information, unequivocal conclusions, understandable interpretations, and clear suggestions about what to do next. Fulfilling these needs, however, is not a simple task for the researcher because outcomes are predicated on statistical uncertainty and the research tests may not be appropriate for individual assessment. We describe methods we have used to communicate with research subjects in two CNS neurotoxic field studies. We suggest that further research examine this important notification process. PMID- 1425503 TI - What is a specialist? The role of board certification in occupational medicine. AB - A shortage of occupational medicine physicians exists for which a number of solutions have been proposed. The lack of board-certified specialists to address the increasingly complex issues encountered in this area of medicine has contributed to a credibility and identity crisis within the occupational medicine community. This article will review the significance of board certification and its importance for enhancing and preserving the specialty of occupational medicine. PMID- 1425504 TI - Occupational and environmental hazards in art. AB - Artists and craftspeople, art teachers, hobbyists, and children often use art materials containing toxic chemicals without suitable precautions and often without the knowledge that their art materials are hazardous. The Center for Safety in the Arts, a national clearinghouse for research and education on hazards in the visual and performing arts, answers telephoned and written inquiries on art hazards, distributes publications, publishes a newsletter, and offers educational programs and consultative services to arts organizations. PMID- 1425505 TI - Expiratory flows decreased in Los Angeles children from 1984 to 1987: is this evidence of effects of air pollution? AB - To estimate the effects of air pollution we measured expiratory flows and vital capacities in 556 Mexican-American Los Angeles children in 1984 and 251 in 1987. They included 106 who were measured in 1984 and 1987 and 145 measured only in 1987. Pulmonary function values were standardized for growth be expressing them as percentages of predicted (% pred) based on sex and height. In 1987 mean values for FEV1 and FEF25-75 were lower by 4.5% pred and 13.6% pred respectively (P < 0.001), while vital capacities were not different in 213 children tested as fifth graders in 1984 and 251 fifth grade children in 1987. For the 106 children tested at both sessions (in second grade in 1984 and in fifth grade in 1987) FVC was also not different but FEV1 was 2.0% pred lower (P < 0.06) and FEF25-75 was 7.0% pred lower (P < 0.001). For the 450 children tested only in 1984 and the 106 retested in 1987 there were no significant differences in mean values for FVC, FEV1, and FEF 25-75. Similarly there were no significant differences between the 1987 mean values for 145 children who were studied longitudinally were not different from the 1984 and 1987 cross-sectional cohorts. Across this interval FEV1 and midflows diminished but vital capacities did not. Airways obstruction worsened during children's residence in Los Angeles from 1984 to 1987 and this is probably due to air pollution. PMID- 1425506 TI - A radiographic survey of public school building maintenance and custodial employees. AB - Analyses of radiographs from a cohort of 457 school maintenance and custodial workers (90 had no employment other than at a school) demonstrated an increased prevalence of abnormalities consistent with asbestos-caused disease. Pleural abnormalities predominated (24 of 29). The abnormalities could not be explained by occupational asbestos exposures which may have occurred prior to school employment. Abnormality prevalence ranged from 1.7% among those with less than 10 years to 37% among those with 30 or more years of public school employment. Laborers and skilled tradesmen with more than 20 years of school employment had a higher prevalence of abnormality (40 and 28%) than the building engineers (14%). In order to ensure that future asbestos exposure and disease risk is minimized in buildings constructed with asbestos-containing materials (ACM), implementation of asbestos hazard identification and abatement must include a rigorous operations and maintenance program. Control of asbestos exposure from in-place ACM is a public health priority. PMID- 1425507 TI - Asbestos-related hazards in developing countries. PMID- 1425508 TI - Chronic liver injury in phenoxy herbicide-exposed Vietnam veterans. AB - Reports of hepatotoxic injury in Vietnam veterans exposed to phenoxy herbicides (mainly, 2,4-D and 2,4,5-T) initiated a retrospective cohort study of veterans self-reporting exposure to Agent Orange (AO) while serving in Vietnam from 1962 to 1971. Historical, medical, and laboratory information was obtained in a subcohort of 100 randomly selected veterans from a pool of 350 registrants. An occupational work exposure ranking system was designed to estimate individual exposure to phenoxy herbicide and its contaminant, dioxin (TCDD). Job classifications were determined by military job codes. Military application of the herbicides used in Vietnam were derived from the National Research Council Report based on the Herbs tapes. Health examination included tests of body systems affected by TCDD and similar agents, e.g., hemopoietic system, cholesterol/lipid metabolism, hepatic function, and skin lesions. Skin rash was utilized as a marker disease, since no case of true chloracne was found among the cohort. The cohort was divided into those with (R) and without (NR) a reported rash during or after the Vietnam tour. The R group had higher frequency (31%) of abnormal liver studies of all types than the NR group (18%). Of the 14 Vietnam veterans with persistent serum transaminase elevations, 86% reported a rash. Abnormal liver functions correlated with herbicide exposure index in both groups, but was more prominent in the R group. Study of the exposure index components showed that the liver abnormalities were related to the months of exposure and not to job classification or exposure rank. Viral hepatitis and alcoholism among both groups accounted for the association between liver abnormalities and cumulative exposure to AO. These data provide strong supportive evidence that chronic liver abnormalities among Vietnam veterans applying to the AO Registry are mainly due to viral or alcoholic causality and not to herbicides and their TCDD contaminant. PMID- 1425509 TI - Fish consumption and reproductive outcomes in Green Bay, Wisconsin. AB - Prenatal exposure to polychlorinated biphenyls (PCBs) and reproductive outcome was determined in a population of 1112 women during 1987-1989. The women studied were from the Green Bay, Wisconsin area, thereby providing a population with potential PCB exposure from Lake Michigan sport fish consumption. All women with positive pregnancy tests from two Green Bay prenatal clinics were asked to complete a self-administered questionnaire on fish consumption, health and reproductive history, and other relevant issues and to provide blood samples for PCB analysis. A positive correlation was found between the amount of Lake Michigan fish mothers claimed to consume and their PCB serum levels. After the pregnancy period, reproductive outcome measures (fetal wastage; stillbirths; and birth weight, birth length, head circumference, ponderal index, and birth weight percentiles for live births) were abstracted from hospital labor reports. Typical negative associations between birth size measures and consumption of caffeine, smoking, and alcohol were found. Birth size was positively associated with gestational age, birth order, weight gain during pregnancy, male babies, and rural residence. Birth size was also associated with PCB exposure; however contrary to expectations, a positive association was found (P < 0.044) for most mothers (the exception being those mothers who gained more than 34 lb during their pregnancy). PCB exposures were lower than the other studies that found that birth size was negatively associated with PCB exposure. PMID- 1425510 TI - Changes in PCB serum concentrations among capacitor manufacturing workers. AB - To assess the elimination of PCBs in humans, PCB concentrations in serum from 165 capacitor manufacturing workers were measured twice within a 46-month interval (March 1976-December 1979). Use of PCBs at the facility was entirely eliminated in 1977. PCB congeners with lower chlorination (LPCBs--mainly tri- and tetrachlorobiphenyls) had decreased in concentration, with six of the LPCB 7 peaks observed by packed column GC showing average reductions of 25-90%. Higher chlorinated PCBs did not decrease significantly as a whole, although three of the six constituent congener peaks showed some decline (15-25%). As expected, decreases in PCB congener concentrations were associated with chlorine substitution configurations known to be amenable to metabolism. PMID- 1425511 TI - Neuropsychological performance among agricultural pesticide applicators. AB - To assess the potential effects on neuropsychiatric performance of chronic occupational exposure to organophosphate insecticides, we performed a prospective longitudinal study of a cohort of apple orchard pesticide applicators and a comparison cohort of beef slaughter-house workers. The study group consisted of 49 applicators and 40 comparison subjects who completed both an initial evaluation (preseason) prior to the onset of the approximately 6-month pesticide spraying season and a follow-up evaluation (postseason) about 1 month following the end of spraying season. The applicator cohort had a greater number (n = 22, 45%) of individuals who identified primary preference for Spanish-language testing than did the comparison cohort (n = 5, 13%). Stratification by language preference revealed no significant differences in background characteristics between the two cohorts, except for fewer years of education in the Spanish language preference applicators versus control subgroups (5.0 +/- 3.1 vs 7.8 +/- 3.7 years, respectively). After controlling for language preference, there were no statistically significant differences between the applicators and control cohorts on neuropsychological subtests of the computerized test battery. Preseason baseline performance on individual tests was a significant predictor of postseason test performance. After controlling for baseline performance, the only statistically significant exposure related across-season changes in neuropsychological performance was for one subtest (Symbol Digit Substitution) and was confined to the Spanish language preference subgroups, with worse adjusted postseason performance among applicators versus controls (P = 0.001). This study found no clear evidence of clinically significant decrements in neuropsychological performance following one 6-month season of pesticide exposure in a cohort of applicators who were felt to have generally low, intermittent, and well-controlled organophosphate exposures. PMID- 1425512 TI - Organophosphate pesticide exposure in a group of Washington State orchard applicators. AB - As part of a study to investigate the potential for organophosphates to cause chronic neurologic sequelae, we assessed the pesticide exposure experience of a group of Washington State apple orchard applicators. Seasonal monitoring of cholinesterase activity for 48 regular organophosphate applicators and a control group of 40 slaughterhouse workers was performed. A subset of the pesticide applicators participated in an in-depth exposure assessment. This involved observation of spraying activities during 1 spray day, as well as cholinesterase monitoring and dermal exposure assessment using a fluorescent tracer in the pesticide formulation. Comparison of seasonal red blood cell cholinesterase change in pesticide workers according to exposure level, characterized by frequency of pesticide spraying and protective equipment use, showed lower cholinesterase levels among higher exposed groups compared to lesser exposed groups. In-depth exposure assessment revealed exposure primarily on the head and hand regions. Subclinical changes (less than 15% inhibition) in red cell cholinesterase correlated well with dermal exposure calculations. This study suggests that cholinesterase monitoring may be a useful biological marker for even subclinical organophosphate pesticide effects. PMID- 1425513 TI - Some hidden history of occupational medicine. PMID- 1425514 TI - Dangerous and cancer-causing properties of products and chemicals in the oil refining and petrochemical industry. VIII. Health effects of motor fuels: carcinogenicity of gasoline--scientific update. AB - 1. Significant increases in tumors of kidney, liver, and other tissues and organs following exposure to gasoline provide sufficient evidence of carcinogenicity. 2. Benzene, a significant component of gasoline, has been established without question as a human carcinogen by IARC, EPA, and WHO. 3. 1,3-Butadiene, a component of gasoline, is a powerful carcinogen in both animals and humans. 4. Sufficient evidence for the carcinogenicity of alkyl benzenes, very significant components of gasoline, has also been established. 5. Human epidemiologic studies show important increases in cancers of the kidney, stomach, brain, pancreas, prostate, lung, and skin as well as hematopoietic and lymphatic leukemias as a result of exposure to gasoline, its components, and its vapors. 6. Stage 2 controls are being implemented to reduce exposure of the human population to gasoline vapors. PMID- 1425515 TI - Morphologic, biochemical, and cytogenetic studies of bone marrow and circulating blood cells in painters exposed to ethylene glycol ethers. AB - In a previous cross-sectional survey, up to 15% of shipyard painters were found to have mild anemia or granulocytopenia, mostly acquired since employment. Environmental studies had suggested a possible etiologic role for ethylene glycol ethers, solvents to which the men were heavily exposed and which have established myelotoxic potential. To exclude alternative hypotheses, examine possible common patterns of injury, and identify potential risk factors and markers for such an effect, the affected painters were further studied. The painters were matched with two groups of controls: exposed painters without evidence of hematologic abnormality on the previous survey and unexposed controls. Altogether 25 subjects were studied by histopathologic examination of bone marrow, cytogenetic studies of marrow cells, and peripheral lymphocytes and peripheral red cell studies of membrane and metabolic function. Except for an unexpected finding of a race associated effect on marrow histology, insignificant differences were seen among the groups in terms of marrow morphology and cellularity, stem cell growth kinetics, and marrow or peripheral cytogenetics. Two metabolic abnormalities of peripheral red cells related to exposure or clinical status of the subjects were found. Pyruvate kinase, an established marker of acquired myelodysplasia, was significantly depressed in the subjects with previously abnormal counts. Although reduced glutathione levels and holoenzyme activities of glutathione reductase (GSHR) did not differ among groups, exposed subjects had decreased saturation of GSHR with flavin adenine dinucleotide which could be restored in vitro, suggesting riboflavin deficiency or impaired riboflavin metabolism. Thus, although a unique pattern of bone marrow injury by histologic or genetic assay attributable to ethylene glycol ethers was not defined, biochemical effects of possible mechanistic importance were identified. The relevance of these findings as subclinical disease markers remains to be established. PMID- 1425516 TI - Blood lead levels in incinerator workers. AB - Questions have been raised concerning the safety of mass burn incineration and its role in solid waste management. In 1989, the New York City Office of Occupational Safety and Health examined air levels of metals in New York City incinerators and found that workers were exposed to air lead levels as high as 2500 micrograms/m3 while cleaning the electrostatic precipitators in the plant. In order to determine the biologic significance of these exposures to the workers, blood samples were taken from 56 incinerator workers and 25 controls and analyzed for lead and erythrocyte protoporphyrin levels. Incinerator workers were found to have a mean blood lead of 11.0 micrograms/dl as compared to the control group level of 7.4 micrograms/dl. Risk factors for increased blood lead levels were analyzed using multiple regression analyses. Wearing a personal protective device "always" or not and the interaction of smoking and cleaning the precipitator more than seven times in the past year were found to be significant predictors for blood lead. These results indicate that lead in municipal incinerator ash from electrostatic precipitators is bioavailable and that the effects of such exposure can be minimized by wearing personal protective devices, not smoking, and rotating the work force to minimize precipitator ash contact. PMID- 1425517 TI - A retrospective mortality cohort study of chrysotile asbestos products workers in Tianjin 1972-1987. AB - The mortality rate of a cohort of asbestos workers was investigated in Tianjin, China, between January 1, 1972, and December 31, 1987. The cohort consisted of 662 males and 510 females, employed in asbestos textiles, friction material, and asbestos cement manufacturing. A statistically significant excess mortality was observed for lung cancer in both males and females (SMR 278 and 427, respectively). An increasing trend in SMR was observed with increasing intervals of exposure as well as with increasing exposure level. A synergistic effect was seen between asbestos exposure and cigarette smoking regarding lung cancer. The ratio of smoking and nonsmoking lung cancer death rates was virtually the same in asbestos and in nonasbestos workers. This ratio was approximately 1.6, a value much less than that reported in other countries. This low ratio appears to reflect the fact that many nonsmokers were in fact passive cigarette smokers. Second, it reflects the fact that most smokers smoked hand-rolled tobacco, since manufactured cigarettes did not become popular in China until 1965. These data confirm the hazards of asbestos exposure in developing countries. PMID- 1425518 TI - The first hundred years of radiation research: what have they taught us? PMID- 1425519 TI - Comparative quantitative evaluation of pleural fibrosis and its effects on pulmonary function in two large asbestos-exposed occupational groups--insulators and sheet metal workers. AB - Two large (N = 1584 and N = 1330) population groups of workers exposed to asbestos as insulators (I) or sheet metal workers (SM) were compared. Prevalence rates of radiographic changes including pleural fibrosis (circumscribed and diffuse) were found to be much higher in I than SM. An integrative index of pleural fibrosis (INDEX) showed similar distribution patterns in the two groups; the effect of INDEX on FVC% predicted was more marked in insulators. Factors that could contribute to this difference are thought to be the higher prevalence of interstitial pulmonary fibrosis (probably including that which is not yet radiologically detectable) in I than in SM, the possibility of more extensive pleural fibrosis in areas not accessible to the standard chest X ray (and thus not affecting INDEX) and a higher proportion of diffuse pleural fibrosis in the I group. PMID- 1425520 TI - Medical surveillance and screening in the workplace: complementary preventive strategies. AB - The terms medical surveillance and medical screening have sometimes been used interchangeably in the occupational medicine literature. Recently attempts have been made to redefine these as mutually exclusive, by nesting surveillance under screening or vice versa, by subsuming both under medical monitoring or periodic examinations, or by eliminating use of the term medical surveillance altogether. In this paper I argue that medical surveillance and medical screening represent discrete concepts and approaches and should be viewed as distinct and complementary secondary preventive components of an occupational health program. Medical surveillance refers to the periodic examination of putatively exposed workers, and is therefore a longitudinal approach. Medical screening refers to the cross-sectional testing or evaluation of a group of workers. Biological monitoring, whether defined narrowly or broadly, focuses on exposure to particular toxicants and should serve as a component of medical surveillance (or of medical screening), not as an independent complement to environmental monitoring. Medical surveillance must function in the context of a comprehensive occupational health program that includes industrial hygiene and education and does not in itself suffice as a comprehensive occupational health program. It is useful to clarify these terms because some of the ethical issues as well as medical controversies over their utility arise from a misunderstanding of what constitutes medical surveillance and how it should be applied. PMID- 1425521 TI - Surveillance around hazardous waste sites: geographic information systems and reproductive outcomes. AB - The purpose of this paper is to discuss the potential for integrating surveillance techniques in reproductive epidemiology with geographic information system technology in order to identify populations at risk around hazardous waste sites. Environmental epidemiologic studies have had problems with estimating or measuring exposures to individuals, and of detecting effects when the exposure is low, but continuous. In addition, exposures around hazardous waste sites are complex and frequently involve chemical mixtures. The birth weight of human babies has been reported to be sensitive to many environmental influences. Birth weight can be analyzed as a continuous variable or as a dichotomous one using the standard cutpoint of 2500 g or less to indicate low birth weight. It has the potential to be a powerful surveillance tool since exposures to the fetus reflect maternal and paternal exposures. The advent of recent environmental regulations pertaining to hazardous waste sites has greatly increased the availability of environmental data for many sites. The major problem with incorporating these data into epidemiologic studies has been with the logistics of data management and analysis. Computer-assisted geographic information systems hold promise in providing capabilities needed to address the data management and analysis requirements for effective epidemiologic studies around to hazardous waste sites. PMID- 1425522 TI - Sentinel pathophysiologic conditions: an adjunct to teaching occupational and environmental disease recognition and history taking. AB - Primary care physicians have an increasingly important role in identifying occupational and environmental (O/E) disease. However, the basic skills in O/E history taking, diagnosis, and management have not been adequately incorporated into traditional American medical education or practice. Reasons for these educational barriers are discussed. A new approach to O/E history taking, based on a modified list of occupational sentinel health events, is described. This list will give medical students and residents a practical, directed approach to recognizing O/E conditions and evaluating exposures in formulating a differential diagnosis. Through improved detection and assessment on the part of primary care physicians, appropriate referrals to occupational health specialists can be made for further investigation and public health surveillance. PMID- 1425523 TI - Dietary treatment of uraemia and the relation to lipoprotein metabolism. PMID- 1425524 TI - Effect of zinc on lean tissue synthesis during recovery from malnutrition. AB - During recovery from severe wasting, malnourished children gain weight at greatly accelerated rates. To determine if additional zinc added to their basal therapeutic diets increased the retention of lean tissue and stimulated protein metabolism, we studied three groups of children taking either the basal diet alone or the basal diet supplemented with either 76 mumol (5 mg) or 153 mumol (10 mg) Zn/kg diet. The zinc-supplemented children gained similar weight and consumed the same amount of diet as the unsupplemented children. Zinc supplementation resulted in a greater net absorption of nitrogen and a higher rate of protein turnover, as estimated from urinary ammonia 15N enrichment after oral [15N]glycine. We conclude that additional zinc affected the composition of newly synthesized tissue and intermediary nitrogen metabolism. PMID- 1425525 TI - Changing from a mixed diet to a Scandinavian vegetarian diet: effects on nutrient intake, food choice, meal pattern and cooking methods. AB - Twenty healthy, non-smoking, normal-weight omnivores volunteered for a nutrition counselling programme and changed from a mixed to a Scandinavian lactovegetarian diet. Dietary surveys were performed before and 3, 6 and 12 months after the dietary shift. The major trends when changing from a mixed diet to a lactovegetarian diet included an increase in the consumption of fruits, berries, vegetables, herbal tea and dairy products, and a decrease in the intake of biscuits and buns, sweets, alcoholic beverages, coffee and tea. There was a total absence of fish, eggs and meat products at 3 and 6 months after the dietary shift. At 12 months after the dietary shift two subjects ate small amounts of these animal products. The energy intake decreased throughout the study. The nutrient intake showed the greatest change between the period before and 3 months after the dietary shift. Between 3, 6 and 12 months after the dietary shift there were only minor changes. The observed change in meal pattern is associated with the change in consumption of various food items, the change in nutrient intake and the change in food preparation methods. Further studies should try to clarify the relationship between meal pattern and food intake, nutrient intake and food preparation methods, because counselling on meal pattern most certainly is more rapid and more easily understood than counselling on food and nutrient intake. PMID- 1425526 TI - Reproducibility and validity of 7-day food records. AB - The reproducibility of the 7-day food record method, as used in The Glostrup Population Studies, has been tested by 40 adult volunteers, mainly hospital staff, recording their dietary intakes in two 7-day periods. To validate the calculated protein intake a 24-h urine specimen was collected from all participants in period II, but for various reasons urine specimens were only obtained from 31 in period I. There were significant differences in the intakes of energy, protein and some vitamins and minerals between the two periods, but the nutrient densities, except for vitamin A, were equal. The mean energy distributions in the diet showed no significant differences between the two periods. The weekly variance ratio (S2within/S2between) was between 0.25 and 0.80 for most nutrients. The only ratios above 1.0 were found for vitamin A, vitamin C, vitamin D, vitamin B12 and chromium, selenium and sodium. The weekly coefficients of variance (CV) were for most nutrients less than 30%. In period II the mean protein intake estimated from the urine samples was 74.7 (+/- 15.9 SD) g/day, whereas the protein intake calculated from the diet records was 70.6 (+/- 18.4) g/day. The average estimated protein intake for the 31 people who collected urine in period I was 72.1 (+/- 18.3) g/day, whereas the calculated intake was 78.0 (+/- 22.7) g/day. In neither period were the mean differences significant. PMID- 1425527 TI - Who completes seven-day food records? AB - This study is an attempt to characterize a group of people who volunteered to complete 7-day food record forms. The group was an age- and sex-stratified random sample, comprising 4807 men and women, born in 1922, 1932, 1942 and 1952, drawn from the Civil Registration System. They all received an invitation to the Glostrup Population Studies in 1982-1984. A total of 49.2% completed a 7-day record form. The percentage of respondents was highest in the older age groups. Women were more willing to participate. There was no difference between the groups regarding body mass index. Marital status had some influence, but school education and vocational training had minor importance. A higher percentage of participants, who had never smoked or had quit smoking, completed the records. The male respondents had a lower weekly consumption of beer. No significant differences could be found between the dietary values of the respondents' and non respondents' food consumption according to a food frequency questionnaire. PMID- 1425528 TI - A seven-year follow-up of a weight reduction programme in Finnish primary health care. AB - The study was carried out to assess the short- and long-term effects of a Finnish Social Insurance Institution (SII) weight reduction programme in overweight primary health care clients and the suitability of the programme for use in health centres. The treatment group consisted of 22 men and 71 women, mean body mass index (BMI) 34.3, divided into 8 subgroups. These subjects participated in a 6-week weight reduction course led by public health nurses. Afterwards, there were six follow-up sessions and weight measurements at about 2-month intervals. A control group of 20 men and 76 women, mean BMI 33.5, received no weight reduction instruction during the 1 year that they served as controls. The weights, serum and high-density lipoprotein (HDL) cholesterol levels as well as blood pressures of the subjects in both groups were measured at entry to the study and at the end of the 1-year period. At that time the treatment group showed a weight reduction of 10.9 kg in men and 5.4 kg in women. The control group showed a mean weight gain of 0.9 kg in men and 0.2 kg in women. HDL cholesterol increased in the treatment group. The blood pressure decreased significantly in the category of subjects with a weight loss exceeding 4 kg weight. At the end of the 7-year follow-up period the mean weight reduction in the treatment group was 8.7 kg in men and 3.5 kg in women. Of men 53% and of women 21% still weighed over 10 kg less than at baseline. Both the clients and public health nurses found the weight reduction programme useful and applicable to health centres, preferably with extended time. The programme has now been adopted nationwide in the Finnish primary health care system. PMID- 1425529 TI - Interpretation of erythrocyte glutathione reductase activation test values for assessing riboflavin status. AB - The erythrocyte glutathione reductase activation test (EGR-AC) is considered to be the best method to assess riboflavin nutritional status. Riboflavin supplementation studies carried out in India have raised doubts about the validity of currently available interpretive guidelines for interpreting the EGR AC test. Changes in EGR-AC values in response to graded doses of riboflavin supplementation were investigated in schoolchildren, aged 7-11 years, belonging to the low-income group. For comparison, unsupplemented well-to-do schoolchildren of similar age group were also examined. The results of the study based on the measurement of EGR-AC by the procedure of Bayoumi and Rosalki (Clinical Chemistry, 1976, Vol. 22, pp. 327-335) with an incubation period of 15 min suggest that the cut-off value for EGR-AC to discriminate between riboflavin deficient and normal children cannot be less than 1.5. PMID- 1425530 TI - Protein restriction and progression of chronic renal failure. PMID- 1425531 TI - A comparison of four methods of estimating the body composition of male endurance athletes. AB - Comparisons were effected of the following four methods of estimating the percent body fat (%BF) of 12 highly trained male endurance athletes (mean +/- SD = 2.20 +/- 4.9 years, 176.8 +/- 5.9 cm 64.2 +/- 6.4 kg): underwater weighing (UWW), total body water (TBW), total body potassium (TBK) and dual-energy X-ray absorptiometry (DEXA). The DEXA mean of 6.8% BF was significantly less (P < 0.05) than those estimated via UWW: 9.7% BF; TBW: 10.6% BF (fat-free mass of FFM = 72.0% H2O); and TBK: 9.7% BF (FFM = 66.6 mmol K.kg-1). Nevertheless, the DEXA % BF correlated 0.746 and 0.737 (both P < 0.01) with those from UWW and TBW, respectively; these were the only correlation coefficients to attain statistical significance (P < or = 0.05). Despite the similar means for UWW, TBW and TBK, 12 of the 36 individual differences between these three methods ranged from 3.2 to 10.4% BF. A critical assumption of UWW, which is regarded by many as the criterion method for the estimation of % BF, is that the FFM has a density of 1.100 g.cm-3. Use of in vivo-measured TBW and bone mineral (via DEXA) for the computation of FFM densities for our subjects, while assuming that the two other components of the FFM (protein and non-bone mineral) remained constant, resulted in scores ranging from 1.09541 to 1.10246 g.cm-3 (mean +/- SD = 1.09881 +/- 0.00254 g.cm-3). FFM and % BF differences between use of a constant FFM density of 1.100 g.cm-3 and the individual values ranged from -1.02 to 0.57 kg (mean +/- SD = -0.28 +/- 0.60 kg) and from -0.9 to 1.7% BF (mean +/- SD = 0.5 +/- 0.9% BF), respectively. It may be concluded that with young male athletes: (1) use of constants based on normal male cadavers yielded similar group means for % BF determined by UWW, TBW and TBK but the DEXA % BF correlated significantly with those from UWW and TBW; and (2) in vivo measurements of individual differences in TBW and bone mineral support the use of conventional UWW for the estimation of % BF. PMID- 1425532 TI - Predictors of weight reduction in obese children. AB - The characteristics of successful and unsuccessful weight losers were studied in 48 obese children (relative weight > 120%) aged 6-15 years who were treated for 1 year and observed for another. Successful weight loss was defined as a decrease in relative weight of > or = 0.8 in the standard deviation score (SDS) at the end of the study. Thirty-two children were treated intensively, 16 with individual counselling and 16 in group therapy, while the remaining 16 children were treated conventionally in a school health care setting. Three children dropped out of the study. In 2 years, the relative body weight decreased by 1.7 SDS in those who were successful weight losers (n = 21, 47%), but remained unchanged in those who had been unsuccessful (n = 24). At baseline there were no differences between the two groups. At 1 year, the successful weight losers had lower body weight (P < 0.05), less lean body mass (0.05) and lower fasting concentrations of circulating insulin (P < 0.01) than the unsuccessful children did. A decrease in mothers' body mass index (BMI) and in documented energy intake over the first year as well as energy intake at 1 year were significant predictors of success at 2 years. The combination of these three predictors resulted in correct classification of about 3/4 of the cases as successful or unsuccessful weight losers. It appears, however, difficult to develop a clinically useful model for predicting the treatment outcome in obese children. PMID- 1425533 TI - Diet of adults living in houses in multiple occupation. AB - This study describes the diet and lifestyle of people living in houses in multiple occupation (HMO). A census was taken from a random sample of 400 HMOs in Southampton. Interviews were carried out with a random sample of 73 adult residents from the HMOs. A group of 34 people recently rehoused by the local council were interviewed for comparison. The HMO group had a lack of adequate cooking facilities compared to the council group. A kitchen was used to cook a meal every day by only 53% of the HMO and 77% of the council group. The HMO group spent more money on rent and food than the council group. Women in the HMO group had lower intakes of protein, fat and calcium than women in the council group. Housing conditions appeared to have some influence on nutrient intake. However, the HMO and council groups behaved in a similar way for a number of dietary habits. In low-income groups such as those studied here, factors other than housing conditions appear to influence food intake. PMID- 1425534 TI - Blood vitamin and lipid levels in overweight and obese women. AB - The study was carried out on 102 obese and overweight women, average age 41.5 years, and 33 control non-obese women matched for age. Fasting venous blood vitamins (ascorbic acid, tocopherol, retinol, carotenes, thiamin, riboflavin, folic acid, pyridoxine), lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, total lipids) and haematological indices were determined. Significantly lower serum antioxidant vitamin levels and a higher prevalence of vitamin deficiency were found in the study group. The study confirmed the high risk of dyslipoproteinaemia and the high frequency of elevated blood pressure in obese women. A correlation between ascorbic acid status, degree of obesity and the incidence of elevated blood pressure was demonstrated. PMID- 1425535 TI - Accuracy of a quantitative food frequency questionnaire applied in elderly Norwegian women. AB - The accuracy (reproducibility and relative validity) of a self-administered quantitative food frequency questionnaire including 180 food items was evaluated. A total of 38 elderly women kept multiple weighed diet records for a total of 14 days over a 6-week period and filled in the questionnaire both before and after this period. Spearman rank correlations between the nutrient intakes from the two questionnaires varied from 0.43 for carbohydrate to 0.88 for energy percentage from alcohol. The median correlation was 0.70. Seven women whose recorded average energy intake was less than 1.17 times their measured basal metabolic rate were excluded from the analysis comparing the questionnaire and the diet records. The first questionnaire gave on the average 10% higher nutrient median values than the records, while the second questionnaire did not in general produce higher values. Unadjusted correlation coefficients comparing intakes measured by the two methods ranged from 0.31 for vitamin C to 0.79 for energy percentage from carbohydrate, the median coefficient being 0.61. On the average 77% of the subjects were classified in the same (+/- 1) quintile in the first food frequency questionnaire and the diet records. The present study indicates that the self administered quantitative food frequency questionnaire is useful for measuring individual or group intakes for a variety of nutrients. PMID- 1425536 TI - Platelet phospholipid fatty acid composition and function in vegans compared with age- and sex-matched omnivore controls. AB - Platelet function and phospholipid composition, plasma lipids and dietary intakes were assessed in 20 vegan subjects and 20 age- and sex-matched omnivore controls. The intakes of saturated fat were lower in the vegans and those of linoleic and linolenic acids were greater. Eicosapentaenoic and docosahexaenoic acids were absent from the diets of the vegans. Plasma total cholesterol and low-density lipoprotein concentrations were lower in the male vegan subjects and those of carotene were greater compared with their controls. The platelet phospholipids of the vegans contained higher proportions of linoleic (18:2n-6) and adrenic (22:4n 6) acids and lower proportions of arachidonic (20:4n-6), eicosapentaenoic (20:5n 3), docosapentaenoic (22:5n-3) and docosahexaenoic (22:6n-3) acids. Template bleeding times, platelet aggregation induced by adenosine diphosphate, compound U44619 and collagen were similar in both groups. PMID- 1425537 TI - Decreased food intake in children with severe dysentery due to Shigella dysenteriae 1 infection. AB - Factors that affect food intake in acute shigellosis were studied in 82 children aged 24-59 months. Children were offered an energy-dense milk-cereal-oil-based diet every 2 h. Food intake was compared between children with Shigella dysenteriae 1 infection and those infected with other Shigella spp (predominantly S. flexneri). Mean energy intake in the first 48 h was 435 kJ/kg.d in children infected with S. dysenteriae 1 and 536 kJ/kg.d in children infected with other Shigella spp (P < 0.001). Febrile children ate significantly (P < 0.05) less food than afebrile ones (469 vs 517 kJ/kg.d). Food intake remained significantly (P < 0.001) less in children infected with S. dysenteriae 1 after controlling for the effect of fever. The results show that food intake is significantly reduced in dysentery due to S. dysenteriae 1 infection compared to that of other Shigella species; however, adequate calorie intake can be maintained by providing frequent energy-dense meals despite anorexia, fever, abdominal pain and diarrhoea. PMID- 1425538 TI - Resistant Starch. Proceedings for the 2nd plenary meeting of EURESTA: European FLAIR Concerted Action No. 11 on physiological implications of the consumption of resistant starch in man. Crete, 29 May-2 June 1991. PMID- 1425539 TI - Acetate in venous blood for determination of carbohydrate malabsorption. PMID- 1425540 TI - COMA dietary reference values and the elderly. PMID- 1425541 TI - Energy expenditure in the elderly. PMID- 1425542 TI - Micronutrients: how important in old age? PMID- 1425543 TI - The fetal origins of diseases of old age. PMID- 1425544 TI - Are we pushing the limits of public health interventions for smoking cessation? AB - The phenomenon of smoking cessation that takes place outside formal programs, which serve a small proportion of smokers, is an important public health issue. Self-help strategies represent an approach to potentially cost-effective smoking intervention that can be conveniently used by large groups of smokers. In this issue of Health Psychology, Gritz, Berman, Bastani, and Wu (1992) demonstrate that the mailing of self-help smoking cessation materials to nonvolunteer women in a health maintenance organization, without any personal contact, produces little behavior change beyond what occurs in the environment without such distribution. This outcome is not surprising and does not illiminate the possibility of efficacious use of self-help materials with a nonvolunteer population. An essential question is: Could these materials have been distributed in such a way as to increase their use and eventual efficacy? Efforts to attract more smokers to use existing materials are an essential element of self-help strategies. An effective public health approach is a comprehensive one that successfully engages the individual and, through multiple channels in the community, provides reinforcement, supports, and norms for not smoking. PMID- 1425545 TI - A randomized trial of a self-help smoking cessation intervention in a nonvolunteer female population: testing the limits of the public health model. AB - Reaching nonvolunteer female smokers with effective smoking cessation programs is a critical public health challenge. Smokers (N = 2,786) among 15,004 female members of a health maintenance organization who completed a routine needs assessment were invited into the "UCLA Preventive Health Behavior Study," consisting of five telephone interviews over 2 years assessing health practices. Participants (N = 1,396) were randomized into experimental or control conditions of an unsolicited, mailed, self-help smoking cessation program. Subjects were not alerted to the link between the program and the health study. Smoking status was assessed at 1, 6, 12, and 18 months. Across all subjects, point prevalence at 18 months was 18.62, and continuous abstinence was 2.71%. No difference was found between treatment and control groups regarding smoking status or readiness to stop smoking--raising questions about the value of mailing cessation materials to nonvolunteers. Quit rates increased over the 18-month follow-up; those still smoking at 18 months reported increased readiness to quit. Predictors at each follow-up point were examined multivariately. PMID- 1425546 TI - Smoking prevention among urban minority youth: assessing effects on outcome and mediating variables. AB - We tested the effectiveness of a social resistance/competence enhancement approach to smoking prevention among predominantly Hispanic seventh graders (N = 3,153) from 47 New York City schools. After blocking on school type (public and parochial) and ethnic composition (percent Hispanic), schools were randomly assigned either to receive the 15-session prevention program or to serve as no contact controls. Using the school as the unit of analysis, significant program effects were found for cigarette smoking, normative expectations concerning peer and adult smoking, smoking prevalence knowledge, social acceptability knowledge, and knowledge of smoking consequences. Using structural modeling techniques, a significant relation was found between the normative expectation and knowledge variables affected by the intervention and posttest smoking, suggesting that changes on these variables mediated the impact of the intervention on cigarette smoking. This study extends the results of previous prevention research and demonstrates the generalizability of this approach to predominantly Hispanic urban minority students. PMID- 1425547 TI - Self-disclosure of HIV infection: preliminary results from a sample of Hispanic men. AB - We examined self-disclosure of HIV infection among 101 seropositive Hispanic men residing in Los Angeles. Results indicated that disclosure was highly selective and presumably influenced by the social, psychological, and material consequences of informing others about one's medical condition. Subjects tended to inform significant others such as parents, friends, and lovers than less significant others such as employers, landlords, and religious leaders. There was a relatively high rate of disclosure (75%) to doctors/dentists who were not treating subjects for HIV infection. Gay and bisexual subjects (89% of the sample) were more inclined to disclose their HIV serostatus to homosexual or bisexual others than to heterosexuals and to inform those who were aware of their sexual orientation. Disclosure increased with severity of disease independently of length of time since testing seropositive. Self-rated negative changes in appearance correlated with disclosure to less significant others. The role of cultural attitudes and values in self-disclosure of HIV infection is discussed. PMID- 1425548 TI - High school students' perceptions of AIDS risk: realistic appraisal or motivated denial? AB - We examined perceptions of risk for acquired immunodeficiency syndrome (AIDS) in 296 high school students living in or near a major urban center. We hypothesized that students with a dispositional tendency to deny threat would be more likely to misperceive their risk of contracting AIDS. Results indicated that study participants, overall, used their behaviors as a basis for assessing personal risk in the sense that they perceived higher risk when their behavior was in fact riskier. However, this relation did not hold for those students classified as repressors on a repression-sensitization scale; repressors' perceptions of absolute (but not comparative) risk were negatively correlated with degree of behavioral risk. In a secondary analysis, perceived absolute risk was found to be a significant predictor of intention to change AIDS-risk behaviors. This study provides support for a motivational interpretation of perceived invulnerability and has implications for the development of models of health behavior change. PMID- 1425550 TI - Improving adherence to fluid restrictions in male hemodialysis patients: a comparison of cognitive and behavioral approaches. AB - A cognitive intervention and a behavioral intervention were compared to determine their relative effectiveness in reducing interdialytic weight gain (IWG) among eight adult male hemodialysis patients. The behavioral model consisted of positive reinforcement, shaping, and self-monitoring. The cognitive model consisted of a counseling intervention designed to modify health beliefs. Three small-sample experimental studies showed that both interventions produced immediate reductions in IWG. However, the behavioral intervention was superior to the cognitive intervention in producing maintenance of reduced weight gain. Combining the interventions resulted in no improvement over the behavioral intervention alone. Continuation of self-monitoring procedures produced maintenance of improvements up to 2 months posttreatment. Repeated-measures analysis of variance showed changes for only the "barriers" dimension of the health belief model (Hartman & Becker, 1978) (p < .001), and this occurred only following or concurrent with adherence behavior change. Suggestions for treatment and future research are offered. PMID- 1425549 TI - Influence of age, sex, and family on Type A and hostile attitudes and behaviors. AB - We describe the influence of age, sex, and family on Type A and hostility indices that have been related to rates of coronary heart disease (CHD). The sample consisted of 120 girls and 95 boys (ages 6 to 18 years) and 141 women and 120 men (ages 31 to 62 years) from 142 families residing in an upper middle class community. Results showed little familial aggregation of Type A and hostility. Adults had higher Structured Interview (SI) Potential for Hostility ratings than did children, whereas children had higher Minnesota Multiphasic Personality Inventory (MMPI)-derived Hostility scores and SI Anger-In ratings than did adults. Male adults and male children had higher SI Potential for Hostility ratings and MMPI-derived Hostility scores than did their female counterparts. The heightened hostility of males may account, in part, for their heightened risk of CHD relative to females'. PMID- 1425552 TI - Hardiness: a review of theory and research. AB - Although a large body of research on hardiness (a personality construct with dimensions of commitment, control, and challenge) has accumulated, several fundamental issues remain unresolved. Although there are several hardiness scales, the properties of these scales have not been compared. There is debate as to whether hardiness is one or several characteristics. Research studying the pathways through which hardiness exerts its effects has not been comprehensively evaluated. Whereas critics have argued that hardiness does not buffer stress, others have suggested that hardiness buffers for working adults, for males, and in prospective analyses. There is also growing concern that hardiness is related to neuroticism. A review of the literature supports the following conclusions: The Dispositional Resilience Scale (DRS) has several advantages over alternative scales; DRS items form three factors that are consistent with hardiness theory; hardiness dimensions generally show low to moderate intercorrelations; the most common way of categorizing subjects as high or low in hardiness is not consistent with hardiness theory; hardiness does not buffer stress, and it does not buffer stress for working adults, for males, or in prospective analyses; both old and new hardiness scales inadvertently measure neuroticism. Recommendations for future research are provided. PMID- 1425551 TI - Smoking cessation among self-quitters. AB - We examined cessation among 630 smokers who quit abruptly on their own. Continuous, complete abstinence rates were 33% at 2 days, 24% at 7 days, 22% at 14 days, 19% at 1 month, 11% at 3 months, 8% at 6 months postcessation, and 3% at 6 months with biochemical verification. Slipping (smoking an average of less than 1 cigarette/day) was common (9% to 15% of subjects) and was a strong predictor of relapse; however, 23% of long-term abstainers slipped at some point. These results challenge beliefs that most smokers can initially stop smoking and that most relapse occurs later on postcessation. PMID- 1425553 TI - Classification of crossed immunoelectrophoretic patterns using digital image processing and artificial neural networks. AB - A method is presented which makes it possible to present crossed immunoelectrophoretic patterns to an artificial neural network. The electrophoretic patterns are presented for the artificial neural network as three dimensional vectors and it is shown that it is possible with this representation to train the network to learn the patterns and classify them. It was found that the ability to generalize was substantially increased by the addition of noise to the input patterns during training. Furthermore, the addition of noise decreased the number of presentations needed to reach the predetermined error level. The trained neural network was able to classify all distorted patterns correctly within an error range of 1%. PMID- 1425554 TI - Electrophoretic study of conformational changes of a human soluble beta-D galactoside-binding lectin upon storage. AB - Human brain lectin (HBL), a beta-galactoside specific soluble lectin, was purified by affinity chromatography. An alkylated derivative of this lectin was also prepared. Both native and modified molecules were conserved at -20 degrees C in the presence or absence of beta-mercaptoethanol, a reducing agent which was described to maintain the lectin activity in vitro or in the presence of beta mercaptoethanol and lactose. The impact of storage conditions, over one year, on the native and derivated lectins, was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, isoelectric focusing and titration curve, using the PhastSystem (Pharmacia). Western-blot analysis using an anti-HBL antibody and size-exclusion high performance liquid chromatography were used to complete the study. The subunit M(r)s were estimated before freezing (T0) and after three and twelve months (T3, T12). They were comparable for all preparations. In all samples tested, isoelectric focusing demonstrated the existence of at least three acidic proteins, with the pI ranging between 4.7-4.9. Titration curves clearly showed pH-dependent conformational changes, resulting in a panel of differently charged molecular species, some of which may be related to different oxidative states of the cysteine residues. We concluded that lectin can be stored at -20 degrees C for at least one year before use as a reagent since the modifications revealed by electrophoretic analysis do not alter the hemagglutination activity and carbohydrate binding properties. The immunoreactivity also remained unchanged. PMID- 1425555 TI - Purification of serum amyloid A and its isoforms from human plasma by hydrophobic interaction chromatography and preparative isoelectric focusing. AB - The present work was aimed at isolating human serum amyloid A, (SAA), an acute phase protein mainly complexed to high density lipoproteins, directly from human plasma without sequential ultracentrifugation of lipoproteins and subsequent delipidation of the apolipoprotein moiety. Hydrophobic-interaction fast-protein liquid chromatography on Octylsepharose, using stepwise gradient elution profiles under dissociating conditions, followed by fast-protein liquid-gel permeation chromatography on a Superdex TM75 column revealed a higher than 95% purity of isolated SAA. Further purification of SAA from coeluting apolipoproteins C and A II was achieved by preparative isoelectric focusing between pH5-7 using a Rotofor apparatus. Separation of the main SAA isoforms, SAA1 (pI 6.5) and SAA1 des-Arg (pI 6.0, lacking the N-terminal arginine), was achieved by anion-exchange fast protein liquid chromatography on a Fractogel EMD DEAE 650-S column. The purity of the SAA1 and SAA1 des-Arg isoforms, thus isolated, was checked by immunochemical techniques and amino acid analysis. With the described method various SAA isoforms can be isolated, purified and separated directly from human plasma/serum without prior ultracentrifugation. PMID- 1425556 TI - A comparison between low background silver diammine and silver nitrate protein stains. AB - Several methods of silver staining of proteins after sodium dodecyl sulfate electrophoresis in polyacrylamide gels were compared. The most rapid methods were found to be less sensitive than more time-consuming methods. Among the long methods, those using glutaraldehyde treatment of the gel and silver diammine complex as the silvering agent were found to be the most sensitive, at the expense of the use of a modified polyacrylamide matrix and higher silver concentrations. PMID- 1425557 TI - Two-dimensional electrophoretic analysis of immunoglobulin patterns in monoclonal gammopathies. AB - Two-dimensional (2-D) electrophoresis was performed on 24 serum samples from patients diagnosed with monoclonal gammopathies. These samples had been shown to have a homogeneous immunoglobulin (M component) by zone electrophoresis and immunofixation. Using 2-D electrophoresis, the nature of this aberrant protein was further analyzed. It has been presumed that the sharp, dark stained band identified by immunofixation was the production of a monoclonal immunoglobulin. The increased resolution afforded by 2-D methodology reveals several different patterns. On 2-D electrophoresis, a monoclonal antibody has a unique pattern. It consists of 3 to 6 strong, restricted heavy chain bands and a single distorted light chain spot. The 3-6 bands are microheterogeneity of the isoelectric point, attributed to posttranslational glycosylation and/or amidation/deamidation. Analysis by 2-D electrophoresis indicated only 5 samples with a true monoclonal pattern. All but 2 of the samples clearly had aberrant immunoglobulin, but interpretation of the pattern would suggest the protein is other than a fully synthesized monoclonal antibody. The samples showed the following: a monoclonal heavy chain pattern with multiple distorted light chain spots, only an aberrant light chain area, only an aberrant heavy chain, and only a polyclonal increase. Several IgG gammopathies had, in addition, concentrations of gamma heavy chain at a reduced size (34 kDa). PMID- 1425558 TI - Rapid high resolution two-dimensional electrophoresis of human sperm proteins. AB - An improved protocol has been developed for two-dimensional gel analysis of human sperm proteins through the application of recent technical advances. Advantages of this protocol consist of increased resolving power, reduced processing time, enhanced reproducibility of staining patterns, and applicability to small quantities of protein. Technical improvements include determination of optimal protein loading (20 micrograms/gel), development of a reliable tube gel casting system, and application of minigel technology. In this study over 500 proteins were resolved with molecular weights ranging from 12,000 to 105,000 and isoelectric points from 5.0 to 8.5. This is a three-fold improvement in resolution over earlier results. A single operator was able to generate two dimensional gels of multiple samples in less than one day. This rapid high resolution technique should facilitate further investigation of human sperm proteins under normal and pathologic conditions. PMID- 1425559 TI - Two-dimensional electrophoresis of cat sera: protein identification by cross reacting antibodies against human serum proteins. AB - After two-dimensional electrophoresis of cat serum, individual proteins were identified by means of cross reacting antibodies against the human protein homologues. Testing by cross reactivities seemed the method of choice because immunoreagents for cat proteins are not easily available. PMID- 1425560 TI - High resolution two-dimensional mapping of tissue-specific polypeptides in the desert locust, Schistocerca gregaria. AB - High resolution two-dimensional gel electrophoresis (2-DE) using immobilized pH gradients was used to map the tissue-specific polypeptides of the desert locust, Schistocerca gregaria. Highly specific comprehensive 2-DE reference maps ("master gels") were developed for the brain, corpus cardiacum, subesophageal ganglion, and hemolymph. The polypeptides were well resolved within the pH 4-7 range in the first dimension and within the 14-94 kDa molecular mass range in the second dimension. PMID- 1425561 TI - Selective influencing of the migration time of SO4(2-) by forming neutral species with Pb2+ in capillary zone electrophoresis. AB - Organic and inorganic anions are analyzed using capillary zone electrophoresis with indirect fluorescence detection. As electrolyte 2,5-dihydroxybenzoic acid is used. By adding Pb2+ to the electrolyte the migration time of SO4(2-) can be selectively influenced and the separation of Cl- and SO4(2-) considerably improved. The fluorescence intensity of 2,5-dihydroxybenzoic acid increases in the presence of Pb2+ up to a concentration of 6*10(-4) mol/L Pb2+. Limits of detection in the lower mumol/L range were obtained. PMID- 1425562 TI - Elimination of sample diffusion and lateral band spreading in isoelectric focusing employing ready-made immobilized pH gradient gels. AB - A simple procedure for the elimination of lateral sample as well as band spreading in precast, ready-made immobilized pH gradient gels is described. Round or rectangular holes are punched in the dry polyacrylamide gels prior to rehydration. The generated wells proved suitable for application of samples containing surfactants such as Nonidet P-40 or 3-[(3-cholamidopropyl) dimethylammonio]-1- propane-sulfonate (CHAPS). Lateral band spreading and precipitation of samples containing up to 9.5 M urea could be completely eliminated by this method. PMID- 1425563 TI - Etienne Grandjean. PMID- 1425564 TI - Alteration of circadian rhythm in shift-working ambulance personnel. Monitoring of salivary cortisol rhythm. AB - In order to investigate the relationship between internal desynchronization and clinical intolerance to shift work, a set of circadian rhythms including salivary cortisol rhythm were monitored in seven shift-working ambulance personnel. Oral temperature, grip strength of both hands, subjective assessment of drowsiness, fatigue and attention were recorded approximately every four hours except during sleep, for seven days. Self-sampling of salivary cortisol, which was suitable evaluation of endocrine rhythm in field studies, was also tried in this study. cosinor (cosine curve fitting) method and power spectral analysis were used for time series data analysis. The internal desynchronizations between rhythms of physiological variables and sleep-wake cycle were observed in shift-working ambulance personnel. The incidence of internal desynchronization seemed to be higher in intolerant subjects, although the difference between tolerant and intolerant subjects did not reach a statistically significant level. The peak time of salivary cortisol rhythm during a twenty-four hour shift was phase advanced as intolerant to shift work showed apparently an atypical circadian pattern of salivary cortisol with an abnormal peak at 21.00 h. In this subject, the clinical intolerance to shift work seemed to be associated with internal desynchronization of circadian rhythms. The present study confirmed the internal desynchronization of the circadian rhythm in physiological rhythms like oral temperature and grip strengths, and was in favour of the hypothesis of an internal desynchronization and clinical intolerance to shift work. The clinical implication of impairment of salivary cortisol rhythm remains to be further investigated. PMID- 1425565 TI - Electromyographic fatigue in neck/shoulder muscles and endurance in women with repetitive work. AB - EMG was recorded with surface electrodes from the trapezius and deltoid muscles during a static endurance test at approximately 20% of maximal voluntary contraction. Objective parameters for localized muscular fatigue were derived from the time course of the root mean square (RMS) and mean power frequency (MPF) of the EMG recordings. Isotonic regression is introduced as a tool for assessment of such parameters. The most pronounced sign of fatigue for trapezius was an increase in the RMS values, while for deltoid it was a decrease in the MPF values. This could be explained by the different functions of the two muscles. The endurance time for a group of 11 women in industrial work with repetitive short-cycled work tasks who were diagnosed with neck/shoulder disorders (tension neck) was significantly shorter (p less than 0.05) than for a group with the same work, but without neck/shoulder disorders (n = 11), and shorter than for a control group (n = 11). Regarding the EMG fatigue measures, there were no significant differences between the three groups. We did not find any relationships between endurance time and the EMG parameters. The results indicate that neck/shoulder disorders were not associated with divergent mechanisms for developing fatigue in the muscles, as recorded with surface EMG. PMID- 1425566 TI - Reducing back stress to nursing personnel: an ergonomic intervention in a nursing home. AB - A prospective epidemiologic study was conducted in two units (140 beds and 57 nursing assistants) of a nursing home to demonstrate the efficacy of an ergonomic intervention strategy to reduce back stress to nursing personnel. The total programme involved the following: determining patient handling tasks perceived to be most stressful by the nursing assistants (NAs); performing an ergonomic evaluation of these tasks; and conducting a laboratory study to select patient transferring devices perceived to produce less physical stress than existing manual patient-handling methods. The intervention phase included training NAs in the use of these devices, modifying toilets and shower rooms, and applying techniques to patient care. Immediately after completing the intervention programme, a post-intervention analysis (which lasted eight months in unit 1 and four months in unit 2) was performed. A biomechanical evaluation of the physical demands required to perform stressful patient-handling tasks showed that the mean compressive force on the L5/S1 disc, the mean hand force required to make a transfer, and the strength requirements (expressed as percentage female population capable) were 1964 N, 122 N, and 83% after intervention as compared to 4751 N, 312 N, and 41% before intervention. Subjectively, the mean rating of perceived exertion was less than 'very light' after intervention as compared to between 'somewhat hard' and 'hard' before intervention. Overall, the mean acceptability rates for the walking belt and the mechanical hoist were 81% and 87% for patient transfers. The incidence rate for back injuries prior to the intervention, 83 per 200,000 work-hours, decreased to 47 per 200,000 work-hours after the intervention. There were no injuries resulting in lost or restricted work days during the last four months of the post-intervention. It is concluded that an appropriate ergonomic intervention programme offers great promise in reducing physical stress and risk of low-back pain to nursing personnel. However, large-scale studies in different nursing homes are needed to confirm the above findings. PMID- 1425567 TI - The effects of armrests and high seat heights on lower-limb joint load and muscular activity during sitting and rising. AB - The loading moment of force on the hip, knee, and ankle joints of nine healthy men rising from four different types of stools were compared, together with the levels of myoelectrical activity (EMG) in four leg muscles. Two types of stool (stand stools) had higher seats than a normal chair. The other two were of ordinary seat height, but one also had armrests. The bodyweight carried by the different stools when sitting was also measured, and the subject estimated the effort required for each trial. The mean maximum knee moment was over 60% lower when rising from the high stool than from 'ordinary' seat height. The difference between the high and low stand stool was also significant (p less than 0.001). Using the high stool or help of the arms reduced the mean maximum hip moment by about 50%. The mean maximum ankle moment was only marginally influenced by the different stools. Knee moment was influenced more by seat height than was hip moment. Vastus lateralis activity was significantly higher when subjects rose from 'ordinary' height than when rising from either stand stool (p less than 0.001). The rectus femoris muscle was little activated and the semitendinosus muscle was activated earlier when rising from higher seat heights. All subjects estimated the effort of rising from the higher stand stool to be lower than from the lower stand stool or from 'ordinary' height without arm rests. It was concluded that stand stools are good alternatives for workers who change frequently between sitting and standing work. PMID- 1425568 TI - Anthropometry of south Indian industrial workmen. AB - This paper presents the results of an anthropometric survey conducted on South Indian male workers in the electronic industry. The data were collected as part of a project to modify work stations that utilized equipment from other countries. A set of 27 body dimensions were taken from a sample of 128 workmen (aged 18-35 years). The anthropometric measurements are compared with those of Indian men from Central, Western, and Northern parts of India and with those of the American, German, and Japanese men. The results indicate that in general the South Indian man is smaller than Central, Western, and Northern Indian men, as well as smaller than men in America, Germany, Japan, and Africa. This difference needs to be allowed for when considering buying and subsequently using imported equipment for the electronics industry in South India. PMID- 1425569 TI - Structural and functional studies on platelet-derived growth factor. PMID- 1425570 TI - Structure of recombinant N-terminal globule of type VI collagen alpha 3 chain and its binding to heparin and hyaluronan. AB - A large portion of the N-terminal globule of human collagen VI was prepared from the culture medium of stably transfected human embryonic kidney cell clones. The recombinant product corresponds to sequence positions 1-1586 of the alpha 3 (VI) chain that consists of eight homologous approximately 200 residue motifs (N9 to N2) being similar to the A domain motif of von Willebrand factor. By ultracentrifugation fragment N9-N2 showed a molecular mass of 180 kDa and an asymmetric shape. Elongated structures that consist of eight small globes (diameter approximately 5 nm) were demonstrated by electron microscopy. The data indicate that each A domain motif represents a separate folding unit which are connected to each other by short protease-sensitive peptide segments. Circular dichroism studies demonstrated about 38% alpha helix, 14% beta sheets and 17% beta turns. Fragment N9-N2 showed binding to heparin which could be abolished by moderate salt concentrations. Heparin binding was assigned to domains N9, N6 and N3 which were obtained after partial proteolysis. Domains N7, N5 and N4 lacked affinity for heparin. In addition, N9-N2 showed strong binding to hyaluronan that required exposure to 6 M urea for full dissociation. Ligand binding studies indicated some affinity of N9-N2 for the triple helical region of collagen VI suggesting a role of the N-terminal globule in the self-assembly of microfibrils. No or only little binding was, however, observed to fibril-forming collagens I and III, several basement membrane proteins and other extracellular proteins. Fragment N9-N2 was also an inactive substrate for cell adhesion. PMID- 1425571 TI - What limits affinity maturation of antibodies in Xenopus--the rate of somatic mutation or the ability to select mutants? AB - Although the Xenopus immunoglobulin heavy chain locus is structurally and functionally similar to mammalian IgH loci, Xenopus antibodies are limited in heterogeneity, and they mature only slightly in affinity during immune responses. During the antibody response of isogenic frogs to DNP-KLH, mu and upsilon cDNA sequences using elements of the VH1 family were cloned, sequenced and compared with germline counterparts. There were zero to four mutations per sequence, mostly single base substitutions, in the framework and CDRs 1 and 2 of VH. No mutations were found in JH. Since the point mutation rate was only 4- to 7-fold lower than that calculated for mice, affinity maturation does not seem to be limited by mutant availability. Because of a relatively low ratio of replacement to silent mutations in the CDRs and a very high ratio of GC to AT base pairs altered by mutation, it is suggested that the problem results from the absence of an effective mechanism for selecting mutants, which in turn might be related to the absence of germinal centers in Xenopus. PMID- 1425572 TI - Emergence of committed B lymphoid progenitors in the developing chicken embryo. AB - The formation of B lymphoid restricted progenitors was followed during chicken embryonic development by monitoring the appearance of the various Ig gene rearrangements (DJH, VHDJH, V lambda J lambda), as a sensitivity that allows the detection of a single rearranged cell. By quantifying the DJH committed progenitor populations, we describe their evolution in different compartments at different developmental stages. The yolk sac is the first site where DJH-positive cells are observed (at days 5-6 of development); via the general circulation, they then seed the various organs while undergoing VHDJH and V lambda J lambda rearrangements, which occur simultaneously but lag behind DJH by one to several days. These progenitor populations decline with time in most lymphoid sites and only expand in the bursa. RAG-1 expression is observed in the bursa in the absence of ongoing rearrangement activity and thus appears to be an improper marker of rearrangement in the chicken. Commitment to the B cell lineage seems to result from an intrinsic cell program, but the survival and expansion of the committed B progenitors require the specific microenvironment of the bursa. PMID- 1425573 TI - Hemin uptake system of Yersinia enterocolitica: similarities with other TonB dependent systems in gram-negative bacteria. AB - The hemin receptor HemR of Yersinia enterocolitica was identified as a 78 kDa iron regulated outer membrane protein. Cells devoid of the HemR receptor as well as cells mutated in the tonB gene were unable to take up hemin as an iron source. The hemin uptake operon from Y. enterocolitica was cloned in Escherichia coli K12 and was shown to encode four proteins: HemP (6.5 kDa), HemR (78 kDa), HemS (42 kDa) and HemT (27 kDa). When expressed in E.coli hemA aroB, a plasmid carrying genes for HemP and HemR allowed growth on hemin as a porphyrin source. Presence of genes for HemP, HemR and HemS was necessary to allow E.coli hemA aroB cells to use hemin as an iron source. The nucleotide sequence of the hemR gene and its promoter region was determined and the amino acid sequence of the HemR receptor deduced. HemR has a signal peptide of 28 amino acids and a typical TonB box at its amino-terminus. Upstream of the first gene in the operon (hemP), a well conserved Fur box was found which is in accordance with the iron-regulated expression of HemR. PMID- 1425574 TI - Reversible phosphorylation--dephosphorylation determines the localization of rab4 during the cell cycle. AB - The ras-like GTP binding protein rab4 is the only known rab protein on endosomes that is phosphorylated during mitosis. Since a large fraction of rab4 accumulates in the cytosol in mitotic cells, we investigated the molecular mechanism controlling membrane association of rab4. We first show that human rab4 is phosphorylated by recombinant mammalian p34cdc2 kinase in vitro. Next, the actual site of phosphorylation and its functional significance were determined using stably transfected CHO cell lines producing high levels of wild type rab4 or rab4 mutants bearing alterations at Ser196, which occurs within a consensus site for p34cdc2 kinase phosphorylation (S196PRR). Mutation of Ser196 to glutamine or aspartic acid completely prevented rab4 phosphorylation in mitotic cells and also blocked its appearance in the cytosol. Neither C-terminal isoprenylation nor carboxymethylation of rab4 was affected by the mutations or by phosphorylation. Finally, dephosphorylation and reassociation of soluble rab4 with membranes occurred upon exit of cells from mitosis. Thus, phosphorylation of Ser196 is directly responsible for the reversible translocation of rab4 into the cytosol of mitotic cells. PMID- 1425575 TI - The internalization signal in the cytoplasmic tail of lysosomal acid phosphatase consists of the hexapeptide PGYRHV. AB - Lysosomal acid phosphatase (LAP) is rapidly internalized from the cell surface due to a tyrosine-containing internalization signal in its 19 amino acid cytoplasmic tail. Measuring the internalization of a series of LAP cytoplasmic tail truncation and substitution mutants revealed that the N-terminal 12 amino acids of the cytoplasmic tail are sufficient for rapid endocytosis and that the hexapeptide 411-PGYRHV-416 is the tyrosine-containing internalization signal. Truncation and substitution mutants of amino acid residues following Val416 can prevent internalization even though these residues do not belong to the internalization signal. It was shown recently that part of the LAP cytoplasmic tail peptide corresponding to 410-PPGY-413 forms a well-ordered beta turn structure in solution. Two-dimensional NMR spectroscopy of two modified LAP tail peptides, in which the single tyrosine was substituted either by phenylalanine or by alanine, revealed that the tendency to form a beta turn is reduced by 25% in the phenylalanine-containing peptide and by approximately 50% in the alanine containing mutant peptide. Our results suggest, that in the short cytoplasmic tail of LAP tyrosine is required for stabilization of the right turn and that the aromatic ring system of the tyrosine residue is a contact point to the putative cytoplasmic receptor. PMID- 1425576 TI - Cytoplasmic delivery of ribozymes leads to efficient reduction in alpha lactalbumin mRNA levels in C127I mouse cells. AB - Ribozymes targeted to five sites along the alpha-lactalbumin (alpha-lac) mRNA were delivered to the cytoplasm of mouse C127I mammary cells using the T7 vaccinia virus delivery system and the amount of alpha-lac mRNA was monitored 24 48 h post-transfection. Three target sites were selected in the alpha-lac coding region (nucleotides 15, 145 and 361) and two were located in the 3' non-coding region (nucleotides 442 and 694). Acting in trans and at a target:ribozyme ratio of 1:1000, ribozymes targeting sites 361 and 694 reduced alpha-lac mRNA by > 80%; another two ribozymes (targeting nucleotides 442 and 145) reduced mRNA levels by 80 and 60% respectively; the fifth ribozyme (targeting nucleotide 15, near the AUG) was largely ineffective. The kinetic activity (kcat) of each ribozyme in vitro was somewhat predictive of the activity of the two ribozymes that targeted nucleotides 361 and 694, but was not predictive of the in vivo activity of the other three ribozymes. Down-regulation of the intracellular levels of alpha-lac paralleled the ribozyme-dependent reduction achieved for mRNA. For site 442, the reduction in both mRNA and protein was attributed to the catalytic activity of the ribozyme rather than to the antisense effects of the flanking arms, because delivery of an engineered (catalytically-inactive) variant had no effect on mRNA levels and a minimal effect on the level of alpha-lac present in the cell. PMID- 1425577 TI - Activation of HIV-1 pre-mRNA 3' processing in vitro requires both an upstream element and TAR. AB - The architecture of the human immunodeficiency virus type 1 (HIV-1) genome presents an intriguing dilemma for the 3' processing of viral transcripts--to disregard a canonical 'core' poly(A) site processing signal present at the 5' end of the transcript and yet to utilize efficiently an identical signal that resides at the 3' end of the message. The choice of processing sites in HIV-1 appears to be influenced by two factors: (i) proximity to the cap site, and (ii) sequences upstream of the core poly(A) site. We now demonstrate that an in vivo-defined upstream element that resides within the U3 region, 76 nucleotides upstream of the AAUAAA hexamer, acts specifically to enhance 3' processing at the HIV-1 core poly(A) site in vitro. We furthermore show that efficient in vitro 3' processing requires the RNA stem-loop structure of TAR, which serves to juxtapose spatially the upstream element and the core poly(A) site. An analysis of the stability of 3' processing complexes formed at the HIV-1 poly(A) site in vitro suggests that the upstream element may function by increasing processing complex stability at the core poly(A) site. PMID- 1425579 TI - High plasticity of multispecific DNA methyltransferases in the region carrying DNA target recognizing enzyme modules. AB - Multispecific cytosine C5 DNA methyltransferases (MTases) methylate more than one specific DNA target. This is due to the presence of several target recognizing domains (TRDs) in these enzymes. Such TRDs form part of a variable centre in the MTase primary sequence, which separates conserved enzyme core sequences responsible for general steps in the methylation reaction. By deleting, rearranging and exchanging several TRDs of multispecific MTases, we demonstrate their modular character; they mediate target recognition independent of a particular TRD or core sequence context. We show also that multispecific MTases can accommodate inert material of non-MTase origin within their variable region without losing their activity. The remarkable plasticity with respect to the material that can be integrated into this region suggests that the enzyme core sequences preceding or following it form separable functional domains. In spite of the documented flexibility multispecific MTases could not be endowed with novel specificities by integration of putative TRDs of monospecific MTases, pointing to differences between multi- and monospecific MTases in the way their core and TRD sequences interact. PMID- 1425580 TI - Epimutation of repeated genes in Ascobolus immersus. AB - Ascobolus immersus artificial gene repeats were shown previously to be subject premeiotically to both cytosine methylation and inactivation. We studied sexual progenies of strains harbouring two wild type copies of the endogenous met2 gene lying either in tandem array or at ectopic unlinked positions, by (i) investigating the methylation status, (ii) searching for mutations and (iii) analysing the inheritance of inactivation both in mitotic and sexual offspring. 100% of the 'tandem' progeny and 64% of the 'ectopic' progeny had methylated repeats and displayed gene inactivation. Similar methylation patterns involving all or most of the cytosine residues within the repeats were observed in both arrangements. The inactivated met2 copies were totally devoid of mutation, as deduced from: (i) extensive restriction site analysis and DNA sequencing; (ii) the finding that all the Met- derivatives tested reverted to prototrophy in selective conditions; and (iii) the finding that an inactivated copy of met2 stripped of its methylation through amplification in Escherichia coli regained activity when reintroduced in A.immersus. In the absence of selection, gene silencing and methylation were faithfully maintained through mitotic divisions and through five successive sexual cycles. Altogether, these data show the epimutational nature of this methylation induced premeiotically (MIP) process. PMID- 1425578 TI - Expression of the E.coli 3-methyladenine DNA glycosylase I gene in mammalian cells reduces the toxic and mutagenic effects of methylating agents. AB - In order to investigate the importance of 3-methyladenine in cellular sensitivity to chemical methylating agents we have constructed retroviral vectors for the integration and expression of the Escherichia coli tag gene in mammalian cells. The tag gene encodes 3-methyladenine DNA glycosylase-1 which specifically removes 3-alkyladenines from DNA. The constructs were introduced into Chinese hamster V79 cells by liposome mediated transfection or into murine haemopoietic stem cells by cocultivation with a lipofected, virus-packaging cell line. In both cases, stable transfectants were selected for resistance to the antibiotic, G418, conferred by expression of the neo gene carried by the vector. Measurements of 3-methyladenine DNA glycosylase activity in cell extracts showed an up to 10-fold increase in cell lines with stably integrated tag gene sequences. These cell lines were significantly more resistant to the cytotoxic effects of methylmethanesulfonate and N-methyl-N-nitrosourea than their parent cell lines, indicating that 3 methyladenine repair is a limiting factor in cellular resistance to these methylating agents. Furthermore, the mutation frequency induced by methylmethanesulfonate was reduced to 50% of normal by expression of 3 methyladenine I activity in the Chinese hamster cells, indicating that m3A is not only a cytotoxic but also a premutagenic lesion in mammalian cells. It is concluded that an alkylation repair gene function of a type only thought to be present in bacteria can yield a hyperresistant phenotype when transferred to mammalian cells. PMID- 1425581 TI - Cell lineage-specific expression of modulo, a dose-dependent modifier of variegation in Drosophila. AB - Variegation in Drosophila is a manifest illustration of the important role played by chromatin structure in gene expression. We have isolated mutants of modulo (mod) and shown that this gene is a dominant suppressor of variegation. Null mutants are recessive lethal with a melanotic tumour phenotype. The mod protein directly binds DNA, which indicates that it may serve to anchor multimeric complexes promoting chromatin compaction and silencing. Using a specific monoclonal antibody we examined by immunocytochemistry the accumulation pattern of mod protein during embryogenesis. The protein is first detected before the blastoderm cellularization in all somatic nuclei, precisely when pericentromeric heterochromatin becomes visible. After the first cell division, mod protein is expressed in lineages of specific embryonic primordia. Based on its dominant phenotype, expression pattern and DNA-binding activity of its product, we propose that mod regulates chromatin structure and activity in specific cell lineages. PMID- 1425582 TI - Mapping of the in vivo start site for leading strand DNA synthesis in plasmid R1. AB - We have previously constructed Escherichia coli strains in which an R1 plasmid is integrated into the origin of chromosome replication, oriC. In such intR1 strains, oriC is inactive and initiation of chromosome replication instead takes place at the integrated R1 origin. Due to the large size of the chromosome, replication intermediates generated at the R1 origin in these strains are considerably more long-lived than those in unintegrated R1 plasmids. We have taken advantage of this and performed primer extensions on total DNA isolated from intR1 strains, and mapped the free 5' DNA ends that were generated as replication intermediates during R1 replication in vivo. The sensitivity of the mapping was considerably improved by the use of a repeated primer extension method (RPE). The free DNA ends were assumed to represent normal in vivo start sites for leading strand DNA synthesis in plasmid R1. The ends were mapped to a short region approximately 380 bp away from the R1 minimal origin, and the positions agreed well with previous in vitro mappings. The same start positions were also utilized in the absence of the DnaA protein, indicating that DnaA is not required for determination of the position at which DNA synthesis starts during initiation of replication at the R1 origin. PMID- 1425583 TI - HU, the major histone-like protein of E. coli, modulates the binding of IHF to oriC. AB - HU is one of the most abundant DNA binding proteins of bacteria. Unlike IHF, integration host factor of Escherichia coli, with which HU shares many properties, including a strong sequence homology and similar predicted structure, HU seems to bind non-specifically to DNA whereas IHF binds to specific sites. In this work we compare the binding characteristics of HU and IHF to a DNA fragment containing the minimal origin of replication of E. coli (oriC) and we analyse the effect of HU on the binding capacity of IHF to this oriC fragment. We show that HU interacts randomly and non-specifically with oriC as opposed to the specific binding of IHF to this same DNA sequence. In addition, we show that HU can modulate the binding of IHF to its specific oriC site. Depending on the relative concentrations of HU and IHF, HU is able either to activate or to inhibit the binding of IHF to oriC. PMID- 1425585 TI - Determination of the base recognition positions of zinc fingers from sequence analysis. AB - The CC/HH zinc finger is a small independently folded DNA recognition motif found in many eukaryotic proteins, which ligates zinc through two cysteine and two histidine ligands. A database of 1340 zinc fingers from 221 proteins has been constructed and a program for analysis of aligned sequences written. This paper describes sequence analysis aimed at determining the amino acid positions that recognize the DNA bases, by comparing two types of sequence variation. Using the idea that long runs of adjacent zinc fingers have arisen from internal gene duplication, the conservation of each position of the finger within the runs was calculated. The conservation of each position of the finger between homologous proteins from different species was also noted. A correlation of the two types of conservation showed clusters of related amino acids. One cluster of three positions was found to be especially variable within long runs, but highly conserved between corresponding fingers of homologous proteins; these positions are predicted to be the base contact positions. They match the amino acid positions that contact the bases in the co-crystal structure determined by Pavletich and Pabo [Science, 240, 809-817 (1991)]. An adjacent cluster of four positions on the plot may also be associated with DNA binding. This analysis shows that the base recognition positions can be identified even in the absence of a known structure for a zinc finger. These results are applicable to zinc fingers where the structure of the complex is unknown, in particular suggesting that the individual finger--DNA interaction seen in the Zif268--DNA structure has been conserved in many zinc finger--DNA interactions. PMID- 1425584 TI - SRY, like HMG1, recognizes sharp angles in DNA. AB - HMG boxes are DNA binding domains present in chromatin proteins, general transcription factors for nucleolar and mitochondrial RNA polymerases, and gene- and tissue-specific transcriptional regulators. The HMG boxes of HMG1, an abundant component of chromatin, interact specifically with four-way junctions, DNA structures that are cross-shaped and contain angles of approximately 60 and 120 degrees between their arms. We show here also that the HMG box of SRY, the protein that determines the expression of male-specific genes in humans, recognizes four-way junction DNAs irrespective of their sequence. In addition, when SRY binds to linear duplex DNA containing its specific target AACAAAG, it produces a sharp bend. Therefore, the interaction between HMG boxes and DNA appears to be predominantly structure-specific. The production of the recognition of a kink in DNA can serve several distinct functions, such as the repair of DNA lesions, the folding of DNA segments with bound transcriptional factors into productive complexes or the wrapping of DNA in chromatin. PMID- 1425586 TI - Laminin A chain: expression during Drosophila development and genomic sequence. AB - A Drosophila laminin A chain gene was characterized as a 14 kb genomic nucleotide sequence which encodes an open reading frame of 3712 amino acids in 15 exons. Overall, this A chain is similar to its vertebrate counterparts, especially in its N- and C-terminal globular domains, but the sequence that forms the laminin A short arm is quite different and larger. Laminin messages appear in newly formed mesoderm and are later prominently expressed in hemocytes, which also synthesize basement membrane collagen IV. The composition of Drosophila basement membranes changes with development. A novel method of tandemly fused RNA probes showed that developmental increases of laminin mRNAs were primarily associated with periods of morphogenesis, and preceded those of collagen IV, a protein strongly expressed during growth. The ratio of A:B1:B2 mRNAs varied little during embryogenesis, with less mRNA for A than B chains. Staining of embryos with antibodies confirmed and extended the information provided by in situ hybridization. Homologs of the G subdomains of this A chain, which occur in interacting regions of agrin, perlecan, laminin and sex steroid binding protein, may be involved in protein associations. PMID- 1425587 TI - Neuronal specificity of the alpha 7 nicotinic acetylcholine receptor promoter develops during morphogenesis of the central nervous system. AB - A transient transfection assay has been developed to analyse promoter activity in neuronal cells freshly dissociated from the chick central nervous system. The assay enabled us to identify cis-acting regulatory elements within the 5' flanking region of the alpha 7 nicotinic acetylcholine receptor gene. In differentiated retina, regulatory elements direct reporter gene expression to a small subset of neurons which has been identified as ganglion cells, i.e. to the population of neurons in which alpha 7 transcripts were localized by in situ hybridization. However, these promoter elements exhibit ubiquitous activity in undifferentiated neural cells and in mesodermal stem cells. Our study supports the idea that alpha 7 regulatory elements acquire their neuronal specificity in the course of embryogenesis. PMID- 1425588 TI - Regulatory pathways governing modulation of fungal gene expression by a virulence attenuating mycovirus. AB - A viral double-stranded RNA associated with virulence attenuation (hypovirulence) in the chestnut blight fungus (Cryphonectria parasitica) has been shown by DNA mediated transformation to be responsible for transmissible hypovirulence. In addition to reduced virulence, the fungal strain harboring this virus exhibits a diverse array of characteristics, termed hypovirulence-associated traits, which distinguish it from an isogenic virus-free strain. We have investigated one of these traits, suppressed lac-1 (laccase) transcript accumulation. Two different and opposing regulatory pathways appear to govern lac-1 transcript levels in the virus-free strain: a stimulatory pathway was found to be dependent on the inositol trisphosphate (IP3) and calcium second messenger systems. A second pathway limiting transcript accumulation was shown to require ongoing protein synthesis. Additionally, changes in the level of lac-1 transcript accumulation were found to be related to modulation of promoter activity and this activity was shown to be suppressed in the virus-containing strain. We conclude that this hypovirulence-associated virus interferes with transduction of an IP3-calcium dependent signal that is required for stimulation of lac-1 transcription. The perturbation of such signal transduction pathways by hypovirulence-associated viruses may account for the manifold symptoms associated with transmissible hypovirulence. PMID- 1425589 TI - p21ras mediates control of IL-2 gene promoter function in T cell activation. AB - It has been shown previously in T cells that stimulation of protein kinase C or the T cell antigen receptor leads to a rapid and persistent activation of p21ras as measured by a dramatic increase in the amount of bound GTP. These stimuli are also known to induce the expression of the T lymphocyte growth factor, interleukin-2 (IL-2), an essential growth factor for the immune system. Receptor induced activation of p21ras has been demonstrated in several cell types but involvement of protein kinase C as an upstream activator of p21ras appears to be unique to T cells. In this study we show that p21ras acts as a component of the protein kinase C and T cell antigen receptor downstream signalling pathway controlling IL-2 gene expression. In the murine T cell line EL4, constitutively active p21ras greatly potentiates the phorbol ester and T cell receptor agonist induced production of IL-2 as measured both by biological assay for the cytokine and by the use of a reporter construct. Active p21ras also partially replaces the requirement for protein kinase C activation in synergizing with a calcium ionophore to induce production of IL-2. Furthermore, using a dominant negative mutant of ras, Ha-rasN17, we show that endogenous ras function is essential for induction of IL-2 expression in response to protein kinase C or T cell receptor stimulation. Activation of ras proteins is thus a necessary but not sufficient event in the induction of IL-2 synthesis. Ras proteins are therefore pivotal signalling molecules in T cell activation. PMID- 1425590 TI - Analysis of the human alpha globin upstream regulatory element (HS-40) in transgenic mice. AB - We have analysed the effect of a 1.4 kb segment of DNA containing the upstream alpha globin regulatory element (HS-40) on human alpha globin gene expression in fetal mice and lines of transgenic mice. High levels of tissue-specific, human alpha mRNA expression were seen in all transgenic animals and in this sense expression was position independent. However, the level of human alpha mRNA expression per integrated gene copy decreased during development and was inversely related to copy number. The limitation in expression with increasing gene copy number was shown to be in cis since homozygotes for the transgene produced twice as much human alpha mRNA as hemizygotes. In many respects HS -40 appears similar to single elements within the previously described beta globin locus control region and in cross breeding experiments we have shown that HS -40 behaves in a similar manner to such elements in transgenic mice. PMID- 1425591 TI - Sequence-specific initiator elements focus initiation of transcription to distinct sites in the yeast TRP4 promoter. AB - Transcription from the yeast TRP4 promoter initiates at two basal (i127 and i76) and three GCN4 dependent (i31, i25 and i12) initiator elements. All of these elements contain not more than one deviation from the earlier proposed initiator consensus sequence PuPuPyPuPu, a pyrimidine nucleotide flanked on either side by two purine nucleotides. A point mutation analysis of these elements in various combinations was performed and revealed that the central pyrimidine nucleotide and at least one of the 3' flanking purine nucleotides of the PuPuPyPuPu consensus sequence are essential but alone not sufficient to define a functional initiator element. Multiple cryptic transcription start sites, which function independently whether they are located on the coding or the non-coding strand, can replace the function of mutated initiator elements and therefore the overall level of transcription initiation is not affected. The sequence specificity is identical for basal and GCN4 dependent initiator elements demonstrating that they are functionally homologous. These findings imply that the role of initiator elements is to 'focus' the start point(s) of transcription to distinct sites located in the region between the site(s) of the assembly of the transcriptional complex and the start codon of translation. PMID- 1425592 TI - A novel downstream regulatory element of the mouse H-2Kb class I major histocompatibility gene. AB - The H-2Kb gene equipped with a minimal promoter (5' deletion up to -61) was fully expressed in transfected fibroblasts, but inactive in transfected embryonal carcinoma cells. A strong transcriptional regulatory element (H2DRE) was identified when a fragment spanning the second exon and second intron was used to activate transient expression of the reporter chloramphenicol acetyltransferase (CAT) gene in mouse Ltk- or NIH3T3 fibroblasts. Its activity was twice that of a construct where the CAT gene was driven by the H-2Kb 5' enhancer region (H2TF1/KBF1 site) and comparable to that of pRSVCAT construct carrying the strong Rous sarcoma virus LTR enhancer. In accord with regulated transcriptional activity of the intact H-2Kb gene, the H2DRE did not activate the CAT expression in P19 mouse embryonal carcinoma cells. The H2DRE did not function as a typical enhancer since its activity was strongly position dependent. Consistent with its anticipated role in transcription regulation, H2DRE displayed more than five target sites for specifically interacting nuclear factors, two of them being present in H-2 positive fibroblasts, but not in H-2 negative teratocarcinoma cells. None of them was cross-competed by sequences of the 5' enhancer. The results of deletion experiments show that H2DRE is the only regulatory region that can activate transcription from the 5' enhancerless H-2Kb gene in mouse L fibroblasts. PMID- 1425593 TI - Functional antagonism between members of the myb family: B-myb inhibits v-myb induced gene activation. AB - The oncogene v-myb and its cellular progenitor c-myb encode nuclear, DNA binding phosphoproteins that control the expression of certain target genes in immature hematopoietic cells. Here, we report the isolation of a myb-related chicken gene, chicken B-myb. We show that expression of B-myb, unlike that of c-myb, is not restricted to hematopoietic cells, suggesting that B-myb functions in a broader spectrum of cell types than c-myb. We have identified the authentic chicken B-myb protein as a nuclear protein of approximately 110 kDa. We show that the B-myb protein specifically recognizes v-myb binding sites in vitro and that binding is mediated by an N-terminally located DNA binding domain. Although B-myb protein recognizes myb binding sites, B-myb fails to transactivate several myb-responsive gene constructs as well as the endogenous myb-responsive gene mim-1. Instead, we find that B-myb represses v-myb- and c-myb-mediated activation of the mim-1 gene, most likely by competing with other myb proteins for binding sites. Our results raise the possibility that B-myb is an inhibitory member of the myb family. PMID- 1425594 TI - Spatial flexibility in ternary complexes between SRF and its accessory proteins. AB - We investigated the sequence requirements for ternary complex formation by the transcription factor SRF and its Ets domain accessory factors Elk-1 and SAP-1. Ternary complex formation is specified by an SRF consensus site CC(A/T)6GG and a neighbouring Ets motif (C/A)(C/A)GGA(A/T), which is contacted by Elk-1/SAP-1. Both the spacing of these sequences and their relative orientation can be substantially altered with little effect on the efficiency of ternary complex formation. Efficient ternary complex formation by Elk-1 is mediated by the B box, a conserved 21 amino acid region located 50 residues C-terminal to the Ets domain, which also acts to inhibit autonomous DNA binding. Binding studies with the isolated Ets domains indicate that ternary complex formation compensates for low affinity Ets domain-DNA interactions. Several naturally occurring SREs containing Ets motifs at different locations to that in the human c-fos SRE allow SAP-1 and Elk-1 recruitment in vitro. We discuss the mechanism of ternary complex formation. PMID- 1425597 TI - Proteolysis is a key process in virus replication. AB - Proteases were amongst the first enzymes to be isolated and crystallized, and the discovery of their existence in viruses and the realization of the vital role they play has given a new lease of life to one of the oldest topics in biochemistry. Already we have seen the discovery of new variations on well studied reaction mechanisms and there is the promise of others to come that may be totally novel. When this is allied to the prospect of developing the knowledge which is beginning to accrue into a much needed antiviral therapy, it is clear that viral proteases and their key role in viral replication will be an increasing focus of attention for some time to come. PMID- 1425596 TI - A system to study transcription by yeast RNA polymerase I within the chromosomal context: functional analysis of the ribosomal DNA enhancer and the RBP1/REB1 binding sites. AB - We have developed a novel system to study transcription by yeast RNA polymerase I (Pol I) of mutated rDNA units within the chromosomal context. For this, complete rDNA units carrying specific oligonucleotide tags in both the 17S and 26S rRNA genes were integrated into the chromosomal rDNA locus. Using this novel system, we analysed the action of the rDNA enhancer in stimulating transcription within the chromosomal context. We found that the enhancer acts as a stimulatory element in both directions, mainly on its two most proximal rRNA operons. Deletion of the sequences between the enhancer and the Pol I promoter in the tagged, integrated unit indicated that this part of the intergenic spacer contains no other transcriptional regulatory elements for Pol I. We also applied the system to study the function of the rDNA binding protein RBP1/REB1. For this purpose, we analysed tagged units in which either one or both of the binding sites for this protein have been inactivated. We found that mutations of both binding sites strongly diminish the transcription of the adjacent operon. The protein is hypothesized to play a crucial role in keeping the chromosomal rDNA units in an optimal spatial configuration by anchoring consecutive enhancers and promoters to the nucle(ol)ar matrix. PMID- 1425598 TI - Cell death in Parkinson's disease. PMID- 1425595 TI - Hormone-regulated v-rel estrogen receptor fusion protein: reversible induction of cell transformation and cellular gene expression. AB - We describe the construction of a v-rel estrogen receptor fusion protein (v relER) which allows the regulation of v-rel oncoprotein activity by hormone. In the presence of estrogen, v-relER readily transformed primary chicken fibroblasts and bone marrow cells in vitro. In both cell types, v-rel-specific transformation was critically dependent on the presence of estrogen or the estrogen agonist 4 hydroxytamoxifen (OHT). Withdrawal of estrogen or application of an estrogen antagonist, ICI164,384 (ICI) caused a reversal of the transformed phenotype. We also demonstrate that the v-relER protein binds to NF-kappa B sites in an estrogen-dependent manner, thereby showing that sequence-specific DNA binding of v-relER is critical for the activation of its transforming capacity. In transient transfection experiments, we failed to demonstrate a clear repressor or activator function of the v-rel moiety in v-relER. However, in v-relER-transformed bone marrow cells, estrogen and OHT induced elevated mRNA levels of two cellular genes whose expression is constitutive and high in v-rel-transformed cells. These results suggest that v-rel might exert part of its activity as an activator of rel-responsive genes. PMID- 1425599 TI - Towards an understanding of C3-C4 photosynthesis. PMID- 1425600 TI - Biosensors: principles and practice. PMID- 1425601 TI - How groups of proteins titrate--a new approach. PMID- 1425602 TI - The biochemistry of blood clotting: the digestion of a liquid to form a solid. PMID- 1425603 TI - The collagen superfamily--diverse structures and assemblies. PMID- 1425604 TI - The repair of DNA alkylation damage by methyltransferases and glycosylases. PMID- 1425605 TI - Endothelins. PMID- 1425607 TI - Characteristics of spontaneous and induced specific-locus mutation in the ad-3 region of Neurospora crassa: utilization in genetic risk assessment. AB - Data from experiments on the induction of specific-locus mutations in model systems are utilized in genetic risk assessment to estimate potential adverse effects in the human population. In such assessments with radiation or chemical mutagens, the following information is required: (1) spontaneous and induced forward-mutation frequencies, (2) dose-response curves for the overall induction of specific-locus mutations, (3) genetic characterization of spontaneous and induced mutations, and (4) dose-response curves for the different genotypic classes. Specific-locus assays in most eukaryote assay systems provide only portions of the information required for genetic risk assessment. In recognition of the need for a more comprehensive data base, a model system was developed for specific-locus studies in Neurospora crassa. The adenine-3 (ad-3) specific-locus assay was modeled after the 2 gene, morphological specific-locus assay in the dilute-short-ear region of the mouse, and it detects forward-mutations at two closely linked loci: ad-3A and ad-3B. The ad-3 assay system has provided precise dose-response curves not only for inactivation, but also the overall induction of ad-3 mutations. The utilization of this assay in experiments with radiation or chemical mutagens has provided a data base on the induction and genetic characterization of specific-locus mutations that is unique among eukaryotic organisms. In this assay, gene/point mutations, multilocus deletion mutations, and 3 different classes of multiple-locus mutations can be identified. The latter consist of specific-locus mutations associated with recessive lethal mutations located either closely linked to the ad-3 region or elsewhere in the genome. The overall data base on the heterozygous effects of X-ray-induced ad-3 mutations demonstrates that such effects are allele specific, genotype specific, and locus specific. There are probably a variety of mechanisms by which the heterozygous effects of individual allelic mutations at different genetic loci can be affected. In conclusion, unless the frequencies of all of the different classes of induced specific-locus mutations are determined, and utilized in genetic risk assessment exercises, the risk of human exposure to environmental mutagens may be grossly underestimated. PMID- 1425606 TI - Development of a specific-locus assay in the ad-3 region of two-component heterokaryons of Neurospora: a review. AB - In recognition of the need for a more comprehensive data base for genetic risk assessment of human exposure to mutagenic agents in the environment, a model system was developed for specific-locus studies in Neurospora crassa. This lower eukaryotic organism permits the utilization of microbial techniques for recovery of large numbers of specific-locus mutations at two closely linked loci as well as their subsequent genetic analysis. In particular, this assay makes possible exploratory experiments with different environmental mutagens to obtain data on a wide variety of experimental conditions. Such data make it possible to study induction kinetics and mutational spectra in a manner that is not as yet feasible in higher eukaryotic organisms. The adenine-3 (ad-3) specific-locus assay was modeled after the 2-gene, morphological specific-locus assay in the dilute-short ear region of the mouse, and it also detects forward-mutations at two closely linked loci, namely, ad-3A and ad-3B. Because ad-3 mutations are recovered by a direct method, based on the accumulation of a reddish-purple pigment in the vacuoles of the mycelium rather than their requirement for adenine, this system is both a morphological and biochemical specific-locus assay. The use of the ad-3 assay system in experiments with different environmental mutagens has provided precise dose-response curves not only for inactivation, but also the overall induction of ad-3 mutations. Genetic characterization of these ad-3 mutations by a series of 3 rapid and simple genetic tests permits the identification of 18 subclasses of gene/point mutations, and 12 subclasses of multilocus deletion mutations. These subclasses also include 3 different classes of multiple-locus mutations with separate sites of recessive lethal damage either in the immediately adjacent regions or elsewhere in the genome. In summary, this specific-locus assay provides a capability that is unique among eukaryotic organisms for the recovery and analysis of genetic damage at 2 closely linked loci. PMID- 1425608 TI - Mechanisms for dominance: Adh heterodimer formation in heterozygotes between ENU or X-ray induced null alleles and normal alleles in Drosophila melanogaster. AB - To study mechanisms for dominance of phenotype, eight ENU- and four X-ray-induced mutations at the alcohol dehydrogenase (Adh) locus were analyzed for partial dominance in their interaction with normal alleles. All ENU and one of the X-ray mutations were single base substitutions; the other three X-ray mutations were 9 21 base deletions. All but one of the 12 mutant alleles were selected for this study because they produced detectable mutant polypeptides, but seven of the 11 producing a peptide could not form dimers with the normal peptide and the enzyme activity of heterozygotes was about half that of normal homozygotes. Four mutations formed dimers with a decreased catalytic efficiency and two of these were near the limit of detectability; these two also inhibited the formation of normal homodimers. The mutant alleles therefore show multiple mechanisms leading to partial enzyme expression in heterozygotes and a wide range of dominance ranging from almost complete recessive to nearly dominant. All amino acid changes in mutant peptides that form dimers are located between amino acids 182 and 194, so this region is not critical for dimerization. It may, however, be an important surface domain for catalyzation. PMID- 1425609 TI - Assessment of oxidative DNA damage in the oxyR-deficient SOS chromotest strain Escherichia coli PQ300. AB - The SOS chromotest is a simple short-term genotoxicity assay measuring the induction of gene sfiA in Escherichia coli K-12. The recent availability of SOS tester strains with additional mutations in DNA repair or protection systems allows testing of DNA damaging compounds for genotoxic specificity. E. coli PQ300 differs from the standard SOS tester strain PQ37 in that it contains an additional mutation in gene oxyR that renders it more sensitive to oxidative genotoxins. The generation of reactive oxygen intermediates (ROI) by hydroperoxides (H2O2, t-butyl hydroperoxide, cumene hydroperoxide), gamma radiation, glucose oxidase, and xanthine oxidase resulted in a more vigorous SOS response in strain PQ300 compared to strain PQ37. PQ300 was also more sensitive than PQ37 for the detection of reducing agents such as ascorbic acid, cysteine, and glutathione, which also alter the redox status of the bacterial cells. However, intercalating agents (adriamycin, bleomycin, and mitomycin C) and the UV and radiomimetic compound 4-nitroquinoline-1-oxide whose DNA damaging potential are known also to involve ROI did not show significant differences between strains PQ37 and PQ300. It is concluded that the oxyR-deficient strain PQ300 is useful for detecting certain classes of genotoxins that change the oxidative/antioxidative balance of tester bacteria in the SOS chromotest. PMID- 1425610 TI - Mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L. AB - Studies of the mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L. (Bignoniaceae), were performed using the liquid preincubation method of the Salmonella/microsome test. At the highest dose tested, 100 micrograms/plate, both compounds showed no mutagenicity and no cytotoxicity toward S. typhimurium strains TA98 and TA100 either in the presence or absence of S9 mix. However, these substances were antimutagens toward 2 aminoanthracene, aflatoxin B1 (in TA98), and dimethylnitrosamine (in TA100); but neither substance inhibited the direct mutagenic activity of 2-(2-furyl)-3-(5 nitro-2-furyl) acrylamide nor that of sodium azide in strains TA98 and TA100, respectively. PMID- 1425611 TI - DNA adduct formation in mice following dermal application of smoke condensates from cigarettes that burn or heat tobacco. AB - A prototype cigarette that heats tobacco (test cigarette), developed by R.J. Reynolds Tobacco Company, has yielded consistently negative results in several in vivo and in vitro genetic toxicology tests. The objective of the present study was to evaluate the potential of cigarette smoke condensate (CSC) from the test cigarette to induce DNA adducts in mouse tissues and compare the results with those obtained with CSC from a reference tobacco-burning cigarette (1R4F). CD-1 mice were skin-painted with CSC from reference and test cigarettes three times a week for 4 weeks. The highest mass of CSC applied was 180 mg "tar" per week per animal for both reference and test cigarette. DNA adducts were analyzed in skin and lung tissues using the 32P-postlabeling method with the P1 nuclease modification. Distinct diagonal radioactive zones (DRZ) were observed in the DNA from both skin and lung tissues of animals dosed with reference CSC, whereas no corresponding DRZ were observed from the DNA of animals dosed with either test CSC or acetone (solvent control). The relative adduct labeling (RAL) values of skin and lung DNA from reference CSC-treated animals were significantly greater than those of the test CSC-treated animals. The RAL values of the test CSC treated animals were no greater than those of solvent controls. The negative results in DNA adduct assays with test CSC are consistent with all previous results of in vivo and in vitro genetic toxicology testing on this cigarette and provide additional evidence that smoke condensate from the test cigarette is not genotoxic. PMID- 1425612 TI - Adrenaline: relationship between infusion rate, plasma concentration, metabolic and haemodynamic effects in volunteers. AB - The present study investigated the relationship between supraphysiological plasma concentrations of adrenaline and the resulting haemodynamic and metabolic effects. Adrenaline was administered at five infusion rates (0.01-0.2 micrograms kg-1 min-1) in an escalating sequence to eight volunteers. The arterial plasma concentration of adrenaline increased from 53 +/- 44 to 4349 +/- 818 ng litre-1 during the highest infusion rate. Typical haemodynamic responses, such as increase in blood pressure and heart rate, were seen. The plasma concentrations of glucose and lactate increased from 5.2 +/- 0.4 to 13.7 +/- 1.3 mmol litre-1 and from 0.9 +/- 0.3 to 4.7 +/- 2.6 mmol litre-1, respectively, during the highest infusion rate without a significant increase in insulin concentration. Non-esterified fatty acids increased from 379 +/- 97 to 1114 +/- 331 mumol litre 1 during the 0.06 microgram kg-1 min-1 infusion rate. Adrenaline had no selective haemodynamic effect. If similar metabolic effects occur in patients during treatment with adrenaline or other sympathomimetics, they may further increase breakdown of energy stores in a situation of increased catabolism, and impair utilization of parenteral nutrition. PMID- 1425613 TI - Comparative effects of halothane associated with verapamil and ischaemia on myocardial metabolism in isolated perfused rat hearts. AB - The association of verapamil with halothane causes ischaemic-like myocardial dysfunction. Using an isolated rat heart model perfused with a radiolabelled fatty acid (123I-labelled iodohexadecenoic acid) as a sensitive marker of ischaemia this study investigated whether or not this dysfunction is of ischaemic origin. Hearts were perfused with a control solution or with solutions containing either 1% of halothane or 150 ng ml-1 of verapamil or the association of 0.75% halothane + 120 ng ml-1 verapamil. The ischaemic group was perfused at a reduced perfusion rate (-50%). Intracellular fate of IHA was assessed, and its esterification ratio computed. Ischaemia and the drugs induced a similar depression of haemodynamics. The esterification ratio in the ischaemic group was significantly higher (0.723 +/- 0.04) than in controls (0.0526 +/- 0.03) and than in the treated groups: halothane (0.533 +/- 0.06), verapamil (0.411 +/- 0.027) or the association halothane+verapamil (0.408 +/- 0.05), suggesting a non-ischaemic origin for the dysfunction caused by halothane-verapamil. PMID- 1425614 TI - Leucocyte migration: effects of in vitro exposure to anaesthetic agents: possible potentiation of effects by adrenaline. AB - The effect on in vitro migration of leucocytes and lymphocytes of various drugs used in anaesthesia have been determined in the concentration range 10(-2) to 10( 6) M. The drugs included, thiopentone, bupivacaine, lignocaine, adrenaline, noradrenaline, hydrocortisone, morphine (with and without preservative), lorazepam, suxamethonium, pancuronium and atropine. Toxicity and effect on random mobility after incubation for 1 and 18 h were also determined. Thiopentone depressed leucocyte function at a concentration of 10(-5) M which is comparable to clinical plasma concentrations. Increasing the duration of exposure of the cells to the drugs significantly lowered the concentrations at which depression of function was observed. At concentrations used during local infiltration in clinical practice, bupivacaine and lignocaine were toxic to both leucocytes and lymphocytes. Adrenaline, whilst having no direct effect on cell function, potentiated the effect of lignocaine. Morphine showed no effect at 10(-4) M, a level 1,000 times greater than the reported toxic plasma levels. However, this level falls within the range reported for drug addicts. No effects were found for the other drugs. PMID- 1425615 TI - Fentanyl increases cerebrospinal fluid pressure in normocapnic volunteers. AB - In a double blind randomized study, the effect of fentanyl 1 microgram kg-1 i.v. or placebo on mean lumbar cerebrospinal fluid pressure (CSFP), mean arterial pressure, cerebral perfusion pressure, transcutaneous PCO2 and heart rate was studied in 10 spontaneously breathing volunteers in the lateral decubitus position via a 22-gauge spinal needle inserted into the subarachnoidal space at level L3/L4. Fentanyl increased mean CSFP (+/- SD) from 12.4 +/- 2.7 mmHg to 16.0 +/- 2.3 mmHg (P < 0.05) without significant changes in the other variables. No significant changes in any of the measured variables were seen after administration of placebo. Cerebral perfusion pressure decreased significantly after fentanyl (P < 0.05). PMID- 1425616 TI - Art and anaesthesia. PMID- 1425617 TI - Sufentanil decreases cerebral blood flow velocity in patients with elevated intracranial pressure. AB - Recent investigations revealed that sufentanil increases cerebral blood flow (CBF) and intracranial pressure (ICP) in dogs and man. The aim of our study was to evaluate the impact of sufentanil on cerebral blood flow velocity and ICP in neurosurgical patients. Eight neurosurgical ICU patients with elevated ICP (> 20 mmHg) were examined. Sufentanil was given in incremental doses of 0.5, 1.0 and 2.0 micrograms kg-1. Cerebral blood flow velocity decreased significantly from 54 +/- 4 cm s-1 to 48 +/- 3 cm s-1 with the dose of 1.0 microgram kg-1 sufentanil and 47 +/- 3 cm s-1 with 2.0 micrograms kg-1, respectively (mean +/- SEM). ICP values did not increase with any of the doses studied. Thus, changes of mean arterial pressure which fell with 1.0 microgram kg-1 and 2.0 micrograms kg-1 reflect cerebral perfusion pressure alterations. Although changes of cerebral blood flow velocity revealed changes in vascular tone, ICP remained unaltered. PMID- 1425618 TI - Local cerebral blood flow and CO2 reactivity during prostaglandin E1-induced hypotension in patients undergoing cerebral aneurysm surgery. AB - The effects of prostaglandin E1 (PGE1) on local cerebral blood flow and CO2 reactivity were studied in 30 patients undergoing cerebral aneurysm surgery in eight of whom the aneurysm had not ruptured and was an incidental finding. The aneurysms were clipped at various intervals depending upon clinical conditions. Blood flow on the open brain surface was measured with a thermal gradient blood flow-meter. Hypotension was initially induced with 0.1 microgram kg-1 min-1 of PGE1 and subsequently adjusted to maintain the mean arterial blood pressure at about 70 mmHg. Local cerebral blood flow and CO2 reactivity were studied during and after PGE1 administration. Both were preserved, but CO2 reactivity values were lower in patients in whom the aneurysm had ruptured than in those in whom it had not ruptured. PGE1 may be an appropriate drug with which to induce hypotension during cerebral aneurysm surgery because cerebral blood flow and CO2 reactivity is preserved. PMID- 1425619 TI - Somatosensory evoked potentials in cerebral aneurysm surgery. AB - Monitoring of median nerve somatosensory evoked potentials (SSEP) during surgery for a basilar artery aneurysm under moderate hypothermia revealed an unexpected loss of the first cortical peak. This was due to compression of the middle cerebral artery under the retractor during the surgical approach to the aneurysm and would have continued unnoticed for some time in the absence of monitoring, possibly resulting in infarction in the territory of the middle cerebral artery. When the surgeon was alerted the artery was released and the evoked potential returned within about 24 min. There was no new focal neurological deficit postoperatively. PMID- 1425620 TI - Clinical pharmacology of ondansetron in postoperative nausea and vomiting. AB - Ondansetron is a 5-HT3 receptor antagonist which is effective and well tolerated as an antiemetic for emesis induced by cancer chemotherapy and radiation therapy, and in the prevention and treatment of postoperative nausea and vomiting. Ondansetron is rapidly absorbed after oral administration (tmax 1.9 h) with an absolute bioavailability of around 60%. Its terminal elimination half-life is 3.5 h and it is extensively hepatically metabolized. Plasma clearance is 0.38 litre h 1 kg-1 and volume of distribution is 1.8 litre kg-1. Plasma clearance is reduced by age (31% reduction) and hepatic failure (80% reduction in severe failure). In patients undergoing general anaesthesia there is a slight prolongation of terminal half-life, which is not of clinical significance. Ondansetron is very well tolerated in volunteer studies. Headache, mild abdominal pain, and constipation occur infrequently. There is no evidence for effects of ondansetron on cardiac function (electrocardiogram, cardiac output, blood pressure and heart rate), and haemostatic function in volunteers and patients. Respiratory depression induced during general anaesthesia is not potentiated by ondansetron. No drug interactions have been noted with temazepam, atracurium, alfentanil and alcohol in man. There are also no interactions seen in animal studies using pentobarbitone, morphine, neostigmine, prednisolone and diazepam. PMID- 1425621 TI - Experience with ondansetron in chemotherapy- and radiotherapy-induced emesis. AB - Nausea and vomiting are frequent and severe side-effects of cancer chemotherapy and radiotherapy, and are ranked by patients as one of the worst consequences of such therapy. Ondansetron prevents emesis by blocking the 5-HT3 receptors associated with the vomiting reflex. It has been studied in patients receiving highly emetogenic (cisplatin) chemotherapy, less emetogenic (non-cisplatin) chemotherapy, and radiotherapy. In all studies in these indications, ondansetron was found to be superior to metoclopramide in the control of nausea and emesis over the first 24 h following treatment, when these side-effects are normally most severe. Ondansetron has also been shown to be effective in children and the elderly in the control of cytotoxic-induced emesis. Additional studies have demonstrated that a single intravenous dose of ondansetron (8 mg or 32 mg) is as effective as a continuous infusion schedule, and an 8 mg twice-daily oral schedule is as effective as an 8 mg three times daily oral schedule. PMID- 1425622 TI - Incidence and aetiology of postoperative nausea and vomiting. AB - The reported incidence of emetic symptoms in surgical patients varies from 8-92%. Intractable postoperative nausea and vomiting remains one of the most unpleasant side-effects experienced by patients postoperatively, both in ambulatory and non ambulatory care, and has potential risks for severe postoperative complications. Multiple factors are associated with an increased risk of developing postoperative nausea and vomiting: age, gender, pre-existing disease, premedication, operative procedure, anaesthetic and analgesic drugs, anaesthetic procedure, and postoperative symptoms. Prophylactic use of anti-emetic premedication is not currently routine practice because not all patients are at serious risk of postoperative nausea and vomiting, and currently available anti emetics carry undesirable side-effects. However, anti-emetic prophylaxis is very valuable for patients at increased risk. If symptoms do develop in the recovery room, several factors need to be considered in order for anti-emetic treatment to be successful. Adequate hydration and pain control should be ensured, tight fitting oxygen masks avoided, and patients should be encouraged to take slow, deep breaths to decrease the sensation of nausea. To avoid side-effects, anti emetics should be administered in minimally effective doses. If the administration of anti-emetics is initially unsuccessful, it may be useful to try a combination of anti-emetic drugs with different mechanisms of action. PMID- 1425623 TI - Pharmacology of ondansetron. AB - Ondansetron is a highly potent and selective antagonist at 5-HT3 receptors. Its anti-emetic actions were first revealed by its ability to antagonize retching and vomiting induced by chemotherapy and radiotherapy in animals and man. Subsequently, the availability of labelled 5-HT3 receptor ligands allowed identification of 5-HT3 receptors, located at highest densities in the area postrema, nucleus tractus solitarius (NTS), in other areas of the brain, and on afferent terminals of the vagus nerve. Postoperative nausea and vomiting may be caused by various factors: the anaesthetic, associated drugs, the surgical procedure, movement of the patient, sex, weight and pain. These factors mediate their effects via the higher brain circuits, the vestibular nuclei, the chemoreceptor trigger zone in the area postrema, or the upper gastrointestinal tract via the vagus nerve, influencing motor and visceral emetic outputs in the hind-brain. It is hypothesized that ondansetron blocks nausea and vomiting by 5 HT3 receptor antagonism at two specific sites: (i) centrally, in the area postrema/NTS; and (ii) peripherally on vagus nerve terminals. The absence of other pharmacological effects of ondansetron ensures an absence of side-effects. PMID- 1425624 TI - The clinical development of ondansetron for use in the prevention and treatment of postoperative nausea and vomiting. AB - An international clinical trial programme has been established to assess the efficacy and safety of ondansetron in the prevention and treatment of postoperative nausea and vomiting. The programme included nine pilot studies and six key placebo-controlled studies. These studies have evaluated both oral and intravenous formulations of ondansetron in the prevention of postoperative nausea and vomiting, and intravenously administered ondansetron in the treatment of established symptoms. Most patients included in the trials were adult women, less than 50 years of age, receiving anaesthesia for gynaecological surgery. The primary efficacy analysis for emesis was based on the assessment of complete response (i.e. absence of emetic episodes or nausea in the first 24 h postoperatively). These trials clearly demonstrated the anti-emetic efficacy of ondansetron in the prevention and treatment of postoperative nausea and vomiting. PMID- 1425625 TI - Prophylactic intravenous ondansetron in female outpatients undergoing gynaecological surgery: a multicentre dose-comparison study. AB - The efficacy and safety of prophylactic intravenous ondansetron in preventing postoperative nausea and vomiting was investigated in a randomized, stratified, double-blind, placebo-controlled, dose-comparison study of 580 ASA physical class I and II female outpatients undergoing gynaecological surgery and receiving general anaesthesia. Patients received either ondansetron 1, 4 or 8 mg, or placebo i.v. immediately prior to a standardized technique for induction and maintenance of anaesthesia. All patients were intubated and received nitrous oxide and a narcotic. All doses of ondansetron were significantly more effective than placebo in preventing emesis over the 24 h postoperative period. Ondansetron significantly decreased nausea and emesis scores over 24 h postoperatively without causing sedation. No changes in laboratory parameters (haematology, blood chemistry, and liver enzymes) or vital signs (heart rate, blood pressure, and respiratory rate) were observed. Headache and dizziness were the most common side effects; however, their incidence was the same as with placebo. Ondansetron was generally well tolerated, as evidenced by an adverse event, laboratory safety, and vital sign profile similar to placebo. Ondansetron 4 mg was found to be the optimal prophylactic i.v. dose for female outpatients over the entire 24 h postoperative period. Higher doses may offer an added benefit in some patients, such as those with a history of nausea and vomiting following general anaesthesia. PMID- 1425626 TI - Ondansetron in the treatment of postoperative nausea and vomiting in ambulatory outpatients: a dose-comparative, stratified, multicentre study. AB - The safety and efficacy of ondansetron were evaluated in the treatment of postoperative nausea and vomiting. Five hundred patients who experienced nausea or vomiting in the Post-Anaesthesia Care Unit within the first 2 h of recovery were randomized to receive either 1, 4, or 8 mg of ondansetron, or placebo. All patients had undergone ambulatory surgery with general endotracheal anaesthesia. Episodes of emesis, nausea scores, adverse events, vital signs, and laboratory values were assessed before and during the 24 h after study drug administration. Patients were evaluated for the first 2 h in the Post-Anaesthesia Care Unit then followed up for the next 22 h. Complete response was defined as no emetic episodes, no nausea or no rescue anti-emetic medication. For the 0-24 h study period, complete response occurred in only 15% of the placebo group compared to 41%, 47%, and 47% in the 1, 4, and 8 mg ondansetron groups, respectively. Mean nausea scores (scale of 0-10) during the initial observation period (0-2 h) were significantly lower for all doses of ondansetron [2.2 (1 mg), 1.7 (4 mg), and 2.1 (8 mg)] compared to placebo (3.0). The optimal dose of ondansetron for the treatment of postoperative nausea and vomiting was found to be 4 mg. All doses of ondansetron were well tolerated. No clinically significant increases in laboratory parameters or alterations in haemodynamic stability occurred in the ondansetron groups compared to placebo. PMID- 1425627 TI - Safety of ondansetron. AB - Ondansetron is a novel 5-HT3 receptor antagonist used for the treatment of cytotoxic-induced emesis and postoperative nausea and vomiting. Safety data from volunteer studies, non-emesis development studies, studies in the treatment of cytotoxic-induced emesis and postoperative nausea and vomiting, and spontaneous case reports, all indicate that ondansetron is well tolerated and has an excellent safety profile. There are no known interactions of ondansetron with other drugs, and no interference with postoperative recovery. PMID- 1425628 TI - Transient and steady-state cardiopulmonary responses to combined rhythmic and isometric exercise. AB - The transient and steady-state cardiopulmonary responses to combined rhythmic (R) and isometric (I) exercise were examined in nine subjects. Isometric exercise at 30% maximal voluntary contraction (MVC) was started 1.5 min prior to either a 50% or 75% maximal oxygen uptake (VO2max) cycle ride and continued for 1.5 min into the 10-min R. Systolic (Pas) and diastolic (P(ad)) blood pressure, heart rate (fc), inspired ventilation volumes (VI), and oxygen uptake (VO2) were recorded every 30 s throughout each experiment. Responses to I effort alone were recorded for comparison with experiments in which the combined exercises were performed during the first 1.5 min when R had not yet begun. Pas responses in the first 1.5 min of I (no R) showed the typical rapid linear increase. Addition of the R effort further increased Pas to levels which remained nearly constant (steady state) throughout R. R alone produced a slower Pas increase to approximately the same steady-state levels as those of the combined R and I exercise. For P(ad), the linear increase which occurred during the first 1.5 min of I was attenuated with the superimposition of R. Following cessation of I, P(ad) fell rapidly during continued R to levels not different from experiments with R alone. The fc during I alone increased slightly. As I continued, the onset of the R induced a further rapid increase in fc to levels not different from R alone. The VI showed a similar response to fc. VO2 during I alone did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425630 TI - Age and training effects on the lactate kinetics of master athletes during maximal exercise. AB - To study the effects of age and training on lactate production in older trained subjects, the lactate kinetics of highly trained cyclists [HT, n = 7; 65 (SEM 1.2) years] and control subjects with low training (LT, n = 7) and of similar age were compared to those of young athletes [YA, n = 7; 26 (SEM 0.7) years], during an incremental exercise test to maximum power. The results showed that the lactacidaemia at maximal oxygen uptake (VO2max) was lower for HT than for LT (P < 0.05) and, in both cases, lower than that of YA (P < 0.001). The respective values were HT: 3.9 (SEM 0.51), LT: 5.36 (SEM 1.12), and YA: 10.3 (SEM 0.63) mmol.l-1. At submaximal powers, however, the difference in lactacidaemia was not significant between HT and YA, although the values for lactacidaemia at VO2max calculated per watt and per watt normalized by body mass were significantly lower for HT (P < 0.001) and LT (P < 0.02). These results would indicate that the decline in power with age induced a decline in lactacidaemia. Yet this loss in power was not the only causative factor; indeed, our results indicated a complementary metabolic influence. In the older subjects training decreased significantly the lactacidaemia for the same submaximal power (P < 0.01) and from 60% of VO2max onwards (P < 0.05); as for YA it postponed the increase and accumulation of lactates. The lactate increase threshold (Thla-,1) was found at 46% VO2max for LT and at 56% VO2max for HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425629 TI - Plasma volume, osmolarity, total protein and electrolytes during treadmill running and cycle ergometer exercise. AB - While haemoconcentration due to loss of plasma volume is well established during cycling, the existence of similar changes during running remains contentious. This study compared the changes in plasma volume and associated blood indices during 60 min of running and cycling at the same relative intensity (approximately 65% VO2max), with all changes referenced to blood indices obtained after 30 min seated at rest on a cycle ergometer. Plasma osmolarity increased similarly with both forms of exercise but was less than predicted for water loss alone, such that there was a net loss of sodium during exercise and of potassium postexercise, with essentially no loss of protein. Plasma volume decreased similarly (approximately 6.5%) in both exercise trials, but while that with cycling was initiated by exercise itself and was essentially maximal within 5 min, the reduction in plasma volume in the running trial was induced by adopting the upright posture and was complete before exercise began. These data would indicate that different mechanisms are responsible for the changes in plasma volume induced by running and cycling, while the similarity of change would suggest that there is a lower limit to any reduction in plasma volume, regardless of mechanism. Furthermore, the observation that the changes in plasma volume were complete before or early in exercise, would imply that oral water ingestion during prolonged exercise, which is essential for thermoregulation, may be more concerned with homeostasis of extravascular water rather than plasma volume. PMID- 1425631 TI - Adaptations to training at the individual anaerobic threshold. AB - The individual anaerobic threshold (Th(an)) is the highest metabolic rate at which blood lactate concentrations can be maintained at a steady-state during prolonged exercise. The purpose of this study was to test the hypothesis that training at the Th(an) would cause a greater change in indicators of training adaptation than would training "around" the Th(an). Three groups of subjects were evaluated before, and again after 4 and 8 weeks of training: a control group, a group which trained continuously for 30 min at the Th(an) intensity (SS), and a group (NSS) which divided the 30 min of training into 7.5-min blocks at intensities which alternated between being below the Th(an) [Th(an) -30% of the difference between Th(an) and maximal oxygen consumption (VO2max)] and above the Th(an) (Th(an) +30% of the difference between Th(an) and VO2max). The VO2max increased significantly from 4.06 to 4.27 l.min-1 in SS and from 3.89 to 4.06 l.min-1 in NSS. The power output (W) at Th(an) increased from 70.5 to 79.8% VO2max in SS and from 71.1 to 80.7% VO2max in NSS. The magnitude of change in VO2max, W at Th(an), % VO2max at Th(an) and in exercise time to exhaustion at the pretraining Th(an) was similar in both trained groups. Vastus lateralis citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase activities increased to the same extent in both trained groups. While all of these training-induced adaptations were statistically significant (P < 0.05), there were no significant changes in any of these variables for the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425632 TI - Cardiovascular reflexes during sustained handgrip exercise: role of muscle fibre composition, potassium and lactate. AB - Six healthy men performed sustained static handgrip exercise for 2 min at 40% maximal voluntary contraction followed by a 6-min recovery period. Heart rate (fc), arterial blood pressures, and forearm blood flow were measured during rest, exercise, and recovery. Potassium ([K+]) and lactate concentrations in blood from a deep forearm vein were analysed at rest and during recovery. Mean arterial pressure (MAP) and fc declined immediately after exercise and had returned to control levels about 2 min into recovery. The time course of the changes in MAP observed during recovery closely paralleled the changes in [K+] (r = 0.800, P < 0.01), whereas the lactate concentration remained elevated throughout the recovery period. The close relationship between MAP and [K+] was also confirmed by experiments in which a 3-min arterial occlusion period was applied during recovery to the exercised arm by an upper arm cuff. The arterial occlusion affected MAP while fc recovered at almost the same rate as in the control experiment. Muscle biopsies were taken from the brachioradialis muscle and analysed for fibre composition and capillary supply. The MAP at the end of static contraction and the [K+] appearing in the effluent blood immediately after contraction were positively correlated to the relative content of fast twitch (% FT) fibres (r = 0.886 for MAP vs % FT fibres, P < 0.05 and r = 0.878 for [K+] vs % FT fibres, P < 0.05). Capillary to fibre ratio showed an inverse correlation to % FT fibres (r = -0.979, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425633 TI - Active and inactive renin after exercise. AB - The effects of graded exercise on plasma concentrations of active and inactive renin were studied in seven healthy men. Exercise was performed on a cycle ergometer at four different exercise intensities (corresponding to 30%, 50%, 80% and 87% of VO2max) for 10 min each. Concentrations of active renin and total renin after activation by trypsin were measured by direct immunoradiometric assay. Non-trypsin-activated renin concentration (inactive) was obtained by subtraction. Active renin concentrations at 30%, 50%, 80% and 87% of VO2max were 1.2, 1.9, 3.1 and 4.6 times higher than the control concentration, respectively. Similar increases in plasma renin concentration, determined by conventional enzymatic assay, were observed at every stage. In contrast, changes in inactive renin concentration were not significant at any stage. Significant increases in noradrenaline concentration were found at every exercise stage, but adrenaline, aldosterone and lactate concentrations were significantly elevated only after exercise at 50%, 80% and 87% of VO2max. The similarity between the changes in concentration of active renin and noradrenaline would suggest that sympathetic nerve activity may have been responsible either for the release of active renin or for the conversion of inactive renin to its active form in the kidney. PMID- 1425634 TI - Relationship between muscle fatigue and oxygen uptake during cycle ergometer exercise with different ramp slope increments. AB - The surface electromyogram (EMG) from active muscle and oxygen uptake (VO2) were studied simultaneously to examine changes of motor unit (MU) activity during exercise tests with different ramp increments. Six male subjects performed four exhausting cycle exercises with different ramp slopes of 10, 20, 30 and 40 W.min 1 on different days. The EMG signals taken from the vastus lateralis muscle were stored on a digital data recorder and converted to obtain the integrated EMG (iEMG). The VO2 was measured, with 20-s intervals, by the mixing chamber method. A non-linear increase in iEMG against work load was observed for each exercise in all subjects. The break point of the linear relationship of iEMG was determined by the crossing point of the two regression lines (iEMGbp). Significant differences were obtained in the exercise intensities corresponding to maximal oxygen uptake (VO2max) and the iEMGbp between 10 and 30, and 10 and 40 W.min-1 ramp exercises (P < 0.05). However, no significant differences were obtained in VO2max and VO2 corresponding to the iEMGbp during the four ramp exercises. With respect to the relationship between VO2 and exercise intensity during the ramp increments, the VO2-exercise intensity slope showed significant differences only for the upper half (i.e. above iEMGbp). These results demonstrated that the VO2max and VO2 at which a nonlinear increase in iEMG was observed were not varied by the change of ramp slopes but by the exercise intensity corresponding to VO2max and the iEMGbp was varied by the change of ramp slopes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425635 TI - The respiratory system as an exercise limiting factor in normal trained subjects. AB - Recently, we have shown that an untrained respiratory system does limit the endurance of submaximal exercise (64% peak oxygen consumption) in normal sedentary subjects. These subjects were able to increase breathing endurance by almost 300% and cycle endurance by 50% after isolated respiratory training. The aim of the present study was to find out if normal, endurance trained subjects would also benefit from respiratory training. Breathing and cycle endurance as well as maximal oxygen consumption (VO2max) and anaerobic threshold were measured in eight subjects. Subsequently, the subjects trained their respiratory muscles for 4 weeks by breathing 85-160 l.min-1 for 30 min daily. Otherwise they continued their habitual endurance training. After respiratory training, the performance tests made at the beginning of the study were repeated. Respiratory training increased breathing endurance from 6.1 (SD 1.8) min to about 40 min. Cycle endurance at the anaerobic threshold [77 (SD 6) %VO2max] was improved from 22.8 (SD 8.3) min to 31.5 (SD 12.6) min while VO2max and the anaerobic threshold remained essentially the same. Therefore, the endurance of respiratory muscles can be improved remarkably even in trained subjects. Respiratory muscle fatigue induced hyperventilation which limited cycle performance at the anaerobic threshold. After respiratory training, minute ventilation for a given exercise intensity was reduced and cycle performance at the anaerobic threshold was prolonged. These results would indicate the respiratory system to be an exercise limiting factor in normal, endurance trained subjects. PMID- 1425636 TI - Brisk walking improves endurance fitness without changing body fatness in previously sedentary women. AB - The purpose of this study was to examine the influence of brisk walking on endurance fitness and the amount and distribution of body fat in previously sedentary women. Twenty eight women [mean age (SEM): 44.9 (1.5) years] followed the walking programme for 1 year, whilst 16 acted as controls [age 44.4 (2.3) years]. Changes in endurance fitness were evaluated by measuring the oxygen uptake (VO2) at a reference blood lactate concentration of 2 mmol.l-1. Two 1.61 km field tests of walking were completed, one at maximal speed and one at a "brisk" speed, as well as a 1.61-km walk on a motorised treadmill. The amount and distribution of body fat was determined by hydrostatic weighing and anthropometry and energy intake was evaluated using the 7-day weighed food intake method. Walkers completed an average of 157 min.week-1 of brisk walking over the year. The following were increased in walkers, relative to controls: brisk walking speed [walkers 1.73 (0.05) m.s-1 vs 1.88 (0.07) m.s-1; controls 1.69 (0.05) m.s-1 vs 1.70 (0.05) m.s-1 at baseline and 12 months respectively, P < 0.01], maximal walking speed and VO2 at 2 mmol.l-1. In addition, brisk walking reduced heart rate and blood lactate concentration during stepping as well as during standard, submaximal treadmill walking. It did not modify either the amount or the distribution of body fat, despite an unchanged energy intake. PMID- 1425637 TI - Effect of exercise to rest ratio on plasma lactate concentration at work rates above and below maximum oxygen uptake. AB - The metabolic and physiological responses to different exercise to rest ratios (E:R) (2:1, 1:1, 1:2) of eight subjects exercising at work rates approximately 10% above and below maximum oxygen uptake (VO2max) were assessed. Each of the six protocols consisted of 15 1-min-long E:R intervals. Total work (kJ), oxygen uptake (VO2), heart rate (fc) and plasma lactate concentrations were monitored. With increases in either E:R or work rate, VO2 and fc increased (P < 0.05). The average (15 min) VO2 and fc ranged from 40 to 81%, and from 62 to 91% of maximum, respectively. Plasma lactate concentrations nearly doubled at each E:R when work rate was increased from 90 to 110% of VO2max and ranged from a low of 1.8 mmol.l 1 (1:2-90) to a high of 10.7 mmol.l-1 (2:1-110). The 2:1-110 protocol elicited plasma lactate concentrations which were approximately 15 times greater than that of rest. These data suggest that plasma lactate concentrations during intermittent exercise are very sensitive to both work rate and exercise duration. PMID- 1425638 TI - Effects of isokinetic training of the knee extensors on isometric strength and peak power output during cycling. AB - Isokinetic training of right and left quadriceps femoris was undertaken three times per week for 16 weeks. One group of subjects (n = 13) trained at an angular velocity of 4.19 rad.s-1 and a second group (n = 10) at 1.05 rad.s-1. A control group (n = 10) performed no training. Maximal voluntary contraction (MVC) of the quadriceps, and peak pedal velocity nu p,peak) and peak power output (Wpeak) during all-out cycling (against loads equivalent to 9, 10, 11, 12, 13 and 14% MVC) were assessed before and after training. The two training groups did not differ significantly from each other in their training response to any of the performance variables (P > 0.05). No significant difference in MVC was observed for any group after the 16-week period (P = 0.167). The post-training increases in average Wpeak (7%) and nu p,peak (6%) during the cycle tests were each significantly different from the control group response (P = 0.018 and P = 0.008, respectively). It is concluded that 16 weeks of isokinetic strength training of the knee extensors is able to significantly improve nu p, peak and Wpeak during spring cycling, an activity which demands considerable involvement of the trained muscle group but with its own distinct pattern of coordination. PMID- 1425639 TI - Effects of isolated and combined exposures to whole-body vibration and noise on auditory-event related brain potentials and psychophysical assessment. AB - Auditory event-related brain potentials (ERP) in response to two different tone stimuli (1.1 kHz or 1 kHz, 80 dB, 50 ms; given by headphones at a regular interstimulus interval of 5 s with a probability distribution of 70:30) were recorded from 12 healthy male subjects (Ss) during four different conditions with two repetitions: A-60 dBA white noise (wN), no whole-body vibration (WBV); B-60 dBA wN plus sinusoidal WBV in the az-direction with a frequency of 2.01 Hz and acceleration of 2 m.s-2 root mean square; C-80 dBA wN, no WBV; D-80 dBA wN plus WBV. Each condition consisted of two runs of about 11 min interrupted by a break of 4 min. During the break with continuing exposure, but without auditory stimuli, Ss judged the difficulty of the tone-detection task and intensity of noise by means of cross-modality matching (CMM). Vibration-synchronous activity in the electrocardiogram was eliminated by a subtraction-technique. Noise caused an attenuation of the N1 and P2 amplitudes and prolongation of P3 latencies. The WBV did not cause systematic ERP effects. Condition B was associated with higher N1 and smaller P3 amplitudes. The factor "condition" had a significant effect on the peak latencies of P3 to target stimuli and the task difficulty judged by CMM. Both effects exhibited significant linear increases in the sequence of conditions A, B, C, D. For the evaluation of exposure conditions at work, it can be suggested that noise has a strong systematic effect which can be enhanced by WBV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425640 TI - Response of the trunk muscles to training assessed by magnetic resonance imaging and muscle strength. AB - A group of 12 sedentary medical students (1 man and 11 women aged 21-27 years) participated in a strength training programme for the trunk muscles lasting 18 weeks. The maximal isometric flexion and extension forces of the trunk muscles were measured before the training and at 18 weeks by dynamometer. The cross sectional area of the back muscles, i.e. erector spinae, multifidus and psoas muscles, was measured from magnetic resonance images (spin echo sequence TR/TE 1500/80, slice thickness 10 mm) obtained at the L4-L5 disc level before the training, at 11 and 18 weeks. During training, no significant change in the body mass or body fat content was found. Muscle forces or muscle cross-sectional area were not related to body mass. There was a significant increase in both trunk muscle cross-sectional area (psoas muscle P < 0.001 and back muscles P < 0.01) and trunk muscle forces (flexion and extension forces P < 0.01) during the training but no direct association between the muscle cross-sectional area and strength of the flexors and extensors was detected before or after the training. PMID- 1425641 TI - Changes in the fibrinolytic system associated with physical conditioning. AB - The effects of physical conditioning on plasma fibrinolytic activity were studied in two groups of subjects. Volunteers not engaged in any sport were compared with individuals having been subjected to aerobic conditioning (middle-distance runners, defined as men running more than 80 km per week). Plasma concentrations of the different components of the fibrinolytic system were evaluated before and immediately after a maximal effort treadmill protocol. Comparison of the resting parameters revealed that under basal conditions for plasma concentrations of plasminogen, fibrinogen, alpha 2-antiplasmin, protein C and protein S there were no differences between the two groups. Concentrations of the fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) were significantly higher in the runners than in the control group, indicating an increased fibrinolytic potential that seemed to be a consequence of the reduced formation of tissue plasminogen activator-plasminogen activator inhibitor (t-PA-PAI) complexes. Acute maximal exercise resulted in pronounced fibrinolysis, evidenced by the elevation of FbDP and FgDP concentrations, in both groups of subjects. The acceleration of the fibrinolytic activity was larger in conditioned individuals, which could be accounted for by a higher t-PA release and reduced formation of t PA-PAI complexes when compared to the untrained subjects. PMID- 1425642 TI - Branched-chain amino acid supplementation during trekking at high altitude. The effects on loss of body mass, body composition, and muscle power. AB - To investigate the influence of a branched-chain amino acid (BCAA) supplementation on chronic hypoxia-related loss of body mass and muscle loss, 16 subjects [age 35.8 (SD 5.6) years] participating in a 21-day trek at a mean altitude of 3,255 (SD 458) m, were divided in two age-, sex- and fitness-matched groups and took either a dietary supplementation of BCAA (5.76, 2.88 and 2.88 g per day of leucine, isoleucine and valine, respectively) or a placebo (PLAC) in a controlled double-blind manner. Daily energy intake at altitude decreased by 4% in both groups compared with sea level. After altitude exposure both groups showed a significant loss of body mass, 1.7% and 2.8% for BCAA and PLAC, respectively. Fat mass had decreased significantly by 11.7% for BCAA and 10.3% for PLAC, whereas BCAA showed a significantly increased lean mass of 1.5%, as opposed to no change in PLAC. Arm muscle cross-sectional area tended to increase in BCAA, whereas there was a significant decrease of 6.8% in PLAC (P < 0.05 between groups). The same tendency, although not significant, was observed for the thigh muscle cross-sectional area. On the whole it seemed that PLAC had been catabolizing whereas BCAA had been synthesizing muscle tissue. Single jump height from a squatted position showed a similar tendency to increase in both groups. Lower limb maximal power decreased less in BCAA than in PLAC (2.4% vs 7.8%, P < 0.05). We concluded that BCAA supplementation may prevent muscle loss during chronic hypobaric hypoxia. PMID- 1425643 TI - Serum cortisol concentration and testosterone to cortisol ratio in elite prepubescent male gymnasts during training. AB - Serum cortisol concentrations and testosterone:cortisol concentration ratios of eight prepubescent elite male gymnasts (mean age 10 years 11 months) and 11 controls (mean age 11 years 1 month) were examined during 5 consecutive training days. During this period, the gymnasts trained 3 h each day with moderate intensity mobility, strength and skill exercises while the controls were relatively sedentary. Blood samples were taken from all the boys in both groups before (1630 hours) and 30 min after (2000 hours) training on 4 days. Serum cortisol concentrations of the gymnasts were not significantly different from those of the controls throughout the experiment. Serum cortisol concentrations of both groups were significantly larger (P < 0.05) at 1630 hours than at 2000 hours, indicating that cortisol secretion followed the typical adult circadian change, seemingly unaltered by training. However, there was a significant decrease (P < 0.05) in the testosterone:cortisol ratio of the gymnasts when compared with controls from day 1 to day 3. After a rest on day 4 the testosterone: cortisol ratio of the gymnasts significantly increased (P < 0.05) but the ratio of the control group also increased indicating that there may have been some day-to-day change by factor(s) other than training. The most obvious factor which may have accounted for the unresponsiveness of serum cortisol concentration to the gymnastics training was that the exercise intensity was too low. However, several days of the training seemed to reduce the anabolic to catabolic balance but further experiments are needed to confirm this finding. PMID- 1425644 TI - Age variation in the upper limit of hearing. AB - The upper limit of hearing was measured in 6105 otologically normal ears of subjects ranging in age from 5 to 89 years. The results are as follows: in each age group from 5 to 59 years in both sexes, the upper limit of hearing showed an approximately normal distribution if a logarithmic scale was used for the upper limit of hearing axis. The mode of the distribution shifted to a lower frequency with increasing age. Over age 60 years, the distribution became much wider. Standard upper limit age curves were established by calculating 10th, 25th, 50th, 75th and 90th percentiles for each age group. From early childhood where no age variation was recognized in conventional audiometry, deterioration of the upper limit of hearing was already in progress. This deterioration was slight between ages 25 and 39 but at ages over 40 it was accelerated and led to so-called presbycousis. The upper limit of hearing was found to be one of the best parameters for showing the quantitative age-related changes in hearing. PMID- 1425645 TI - Reliability of measurement of oxygen uptake by a portable telemetric system. AB - The purpose of the present study was to check the reliability of measurements of oxygen uptake (VO2) using a newly developed portable telemetry system. This system (K2) consisted of a face mask, a flow meter, a gas analyser with a transmitter, and a receiver. The total mass for the subject to carry was about 850 g. Three experiments were carried out, firstly to check the reliability and reproducibility of the flow meter and the K2 gas analyser, secondly to check the accuracy of K2 by comparing it with the Douglas bag method (DB), and thirdly to apply K2 to sports activities. In the first experiment, the flow meter was highly accurate up to 180 l.min-1 with good reproducibility. The measurement error of the gas analyser was less than 2%. In the second experiment, there was no significant difference in the calculated ventilation between K2 and DB. The VO2 showed no significant difference between K2 and DB with some exceptions. In the third experiment, we succeeded in the measurement of VO2 during rowing on water. The measurement of VO2 during running and playing soccer was also possible. It would seem that the present system could well be a powerful tool in the field measurement of VO2 during various sports activities. PMID- 1425646 TI - A test of the maximum-power stimulus theory for strength. AB - The main purpose was to test the hypothesis that the true force and power in weightlifting were related significantly to the strengthening stimulus. Secondary hypotheses were (a) slower, heavier weight training for strength would increase strength, not maximum power, (b) faster, lighter weight training for maximum power would increase maximum power, not strength and (c) there would be no significant difference between force = mass (F = m) and true force = mass multiplied by acceleration (F = ma) for arm weightlifting. Using an optical encoder, digital recorder and a data-logging computer on an arm weightlifting machine, F = m and F = ma were significantly different between 25% and 94%, contrary to published reports, but not at 100% of strength. A second-order polynomial equation predicted force, F = ma, as a multiple of the weight lifted, from the velocity of the lift with R2 = 0.997. A group was trained for strength and a matched group was trained for maximum power. The strength group gained significantly in maximum power and the power group gained significantly in strength and maximum power. Both groups gained significantly in velocity, but not force, at maximum power. The correlations between strength and maximum power were high (r = 0.95-0.98, P < 0.02), consistent (before and after training) and valid (gain in standard error of estimate of 6 N or 2% of strength). The evidence suggested that maximum power was the strength stimulus. The maximum-power stimulus theory may unify and simplify theories of response and adaptation of structure and function induced by muscle. PMID- 1425647 TI - Oxygen consumption following exercise of moderate intensity and duration. AB - To study the effects of exercise intensity and duration on excess postexercise oxygen consumption (EPOC), 8 men [age = 27.6 (SD 3.8) years, VO2max = 46.1 (SD 8.5) ml min-1 kg-1] performed four randomly assigned cycle-ergometer tests (20 min at 60% VO2max, 40 min at 60% VO2max, 20 min at 70% VO2max, and 40 min at 70% VO2max). O2 uptake, heart rate and rectal temperature were measured before, during, and for 1 h following the exercise tests. Blood for plasma lactate measurements was obtained via cannulae before, and at selected times, during and following exercise. VO2 rapidly declined to preexercise levels following each of the four testing sessions, and there were no differences in EPOC between the sessions. Blood lactate and rectal temperature increased (P < 0.05) with exercise, but had returned to preexercise levels by 40 min of recovery. The results indicate that VO2 returned to resting levels within 40 min after the end of exercise, regardless of the intensity (60% and 70% VO2max) or duration (20 min and 40 min) of the exercise, in men with a moderate aerobic fitness level. PMID- 1425648 TI - Rewarming of feet by lower and upper body exercise. AB - The capacity of different types of exercise to rewarm the body, especially the feet, was studied. Six healthy male subjects wearing winter clothing (2.4 clo, 0.37 degrees C.m2.W-1) were exposed on three occasions to -15 degrees C for 120 min. For the first 60 min the subjects were cooled while sitting motionless and for the latter 60 min they were submitted to cycle ergometer exercise (CE), arm ergometer exercise (AE) or step exercise (ST). The rate of work in CE (about 350 W) served as a reference value for AE and ST. The cooling resulted in an average 1.7 (SEM 0.03) degrees C decrease in mean body temperature (Tb) corresponding to a 425 (SEM 9) kJ heat debt. The ST increased most effectively mean skin, rectal and lower body skin temperatures as well as dry heat loss. The ST increased Tb by 0.83 (SEM 0.16) degrees C, CE by 0.10 (SEM 0.11) degrees C and AE by only 0.07 (SEM 0.12) degrees C. At the end of the exercise the foot temperature was approximately 6 degrees C higher in ST than in CE. The superior rewarming by ST was apparently due to its low mechanical efficiency. Because the increase in Tb could not explain all the changes in foot temperatures, increased circulation and metabolism of the feet would also appear to have been involved. PMID- 1425649 TI - Measurement of fibre pennation using ultrasound in the human quadriceps in vivo. AB - Real-time ultrasound scanning was used to measure the angles of fibre pennation of vastus lateralis (VL) and vastus intermedius (VI) of the human quadriceps (n = 12) in vivo. The maximum isometric force and cross-sectional area of the quadriceps were also measured. With the knee at right-angles the mean fibre angles for VL and VI respectively were 0.133 (0.021) rad [7.6 degrees (1.2 degrees)] and 0.143 (0.028) rad [8.2 degrees (1.6 degrees)] [mean (SD)], which is within the range of angles measured on cadavers. The mean angle decreased in going from the contracted [VL, 0.244 rad (14 degrees); VI, 0.279 rad (16 degrees)] to the stretched [VL, 0.105 rad (6 degrees); VI, 0.122 rad (7 degrees)] position. There was a significant positive correlation between fibre angle and muscle cross-sectional area but no relationship between fibre angle and force per cross-sectional area. No increase in fibre angle was detected after 3 months strength training. We conclude that ultrasound can be used to measure pennation angles of superficial muscle groups but we could not demonstrate a relationship between pennation and force-generating capacity. PMID- 1425650 TI - Assessment of human knee extensor muscles stress from in vivo physiological cross sectional area and strength measurements. AB - The physiological cross-sectional areas (CSAp) of the vastus lateralis (VL), vastus intermedius (VI), vastus medialis (VM) and rectus femoris (RF) were obtained, in vivo, from the reconstructed muscle volumes, angles of pennation and distance between tendons of six healthy male volunteers by nuclear magnetic resonance imaging (MRI). In all subjects, the isometric maximum voluntary contraction strength (MVC) was measured at the optimum angle at which peak force occurred. The MVC developed at the ankle was 746.0 (SD 141.8) N and its tendon component (Ft), given by a mechanical advantage of 0.117 (SD 0.010), was 6.367 (SD 1.113) kN. To calculate the force acting along the fibres (Ff) of each muscle, Ft was divided by the cosine of the angle of pennation and multiplied for (CSAp.sigma CSAp-1), where sigma CSAp was the sum of CSAp of the four muscles. The resulting Ff values of VL, VI, VM and RF were: 1.452 (SD 0.531) kN, 1.997 (SD 0.187) kN, 1.914 (SD 0.827) kN, and 1.601 (SD 0.306) kN, respectively. The stress of each muscle was obtained by dividing these forces for the respective CSAp which was: 6.24 x 10(-3) (SD 2.54 x 10(-3)) m2 for VL, 8.35 x 10(-3) (SD 1.17 x 10(-3)) m2 for VI, 6.80 x 10(-3) (SD 2.66 x 10(-3)) m2 for VM and 6.62 x 10(-3) (SD 1.21 x 10(-3)) m2 for RF. The mean value of stress of VL, VI, VM and RF was 250 (SD 19) kN m-2; this value is in good agreement with data on animal muscle and those on human parallel-fibred muscle. PMID- 1425651 TI - Fluid replacement beverages and maintenance of plasma volume during exercise: role of aldosterone and vasopressin. AB - Previous experiments have demonstrated that consumption of a glucose polymer electrolyte (GP-E) beverage is superior to water in minimizing exercise-induced decreases in plasma volume (PV). We tested the hypothesis that elevated plasma concentrations of vasopressin and/or aldosterone above that seen with water ingestion may explain this observation. Six trained cyclists performed 115 min of constant-load exercise (approximately 65% of maximal oxygen consumption) on a cycle ergometer on two occasions with 7 days separating experiments. Ambient conditions were maintained relatively constant for both exercise tests (29-30 degrees C; 58-66% relative humidity). During each experiment, subjects consumed 400 ml of one of the following beverages 20 min prior to exercise and 275 ml immediately prior to and every 15 min during exercise: (1) distilled water or (2) GP-E drink contents = 7% carbohydrate (glucose polymers and fructose; 9 mmol.l-1 sodium; 5 mmol.l-1 potassium; osmolality 250 mosmol.l-1). No significant difference (P > 0.05) existed in mean skin temperature, rectal temperature, oxygen consumption, carbon dioxide production or the respiratory exchange ratio between treatments. Further, no significant differences existed in plasma osmolality and plasma concentrations of sodium, potassium, chloride or magnesium between treatments. Plasma volume was better maintained (P < 0.05) in the GP-E trial at 90 and 120 min of exercise when compared to the water treatment. No differences existed in plasma levels of vasopressin or aldosterone between treatments at any measurement period. Further, the correlation coefficients between plasma concentrations of vasopressin and aldosterone and change in PV during exercise were 0.42 (P < 0.05) and 0.16 (P > 0.05), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425652 TI - Effect of very low calorie diet on body composition and exercise response in sedentary women. AB - The effect of very low calorie diet (VLCD) on fat-free mass (FFM) and physiological response to exercise is a topic of current interest. Ten moderately obese women (aged 23-57 years) received VLCD (1695 kJ.day-1) for 6 weeks. FFM, estimated by four conventional techniques, and heart rate (fc), blood lactate (la(b)), mean arterial pressure (MAP), respiratory exchange ratio (R) and rating of perceived exertion (RPE) were measured during a submaximal cycle ergometry test 1 week before, in the 2nd and 6th week, and 1 week after VLCD treatment. Strength and muscular endurance of the quadriceps and hamstrings were tested by isokinetic dynamometry. The 11.5-kg reduction in body mass was approximately 63% fat and 37% FFM. The latter was attributed largely to the loss of water associated with glycogen. Whilst exercise fc increased by 9-14 beats.min-1 (P < 0.01), there were substantial decreases (P < 0.01) in submaximal MAP (1.07-1.73 kPa), la(b) (0.75-1.00 mmol.l-1 and R (0.07-0.09) during VLCD. R and fc returned to normal levels after VLCD. Gross strength decreased (P < 0.01) by 9 and 13% at 1.05 rad.s-1 and 3.14 rad.s-1, respectively. Strength expressed relative to body mass (Nm.kg-1) increased (P < 0.01) at the lower contraction velocity, but there was no change at the faster velocity. Muscular endurance also decreased (P < 0.01) by 62 and 82% for the hamstrings and quadriceps, respectively. We concluded that the strength decrease was a natural adaptation to the reduction in body mass as the ratio of strength to FFM was maintained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425653 TI - The effects of two levels of caffeine ingestion on excess postexercise oxygen consumption in untrained women. AB - The effects of two levels of caffeine ingestion (5 mg.kg-1, CAF1, and 10 mg.kg-1, CAF2) on postexercise oxygen consumption was investigated in six untrained women aged 20.5 (SEM 0.5) years. After a test to determine maximal oxygen consumption (VO2max) each subject underwent three test sessions at 55% VO2max either in a control condition (CON) or with the CAF1 or CAF2 dose of caffeine. During exercise, oxygen consumption was found to be significantly higher in the CAF1 and CAF2 trials, compared to CON (P < 0.05). During the hour postexercise, oxygen consumption in CAF1 and CAF2 remained significantly higher than in CON (P < 0.05). At all times throughout the exercise, free fatty acid (FFA) concentrations were significantly higher in the caffeine trials than in CON. The FFA concentrations 1 h postexercise (+60 min) were further elevated above resting values for all three trials. Caffeine ingestion caused the greatest elevation above resting levels being 1.89 (SEM 0.19) mmol.l-1 and 1.96 (SEM 0.22) mmol.l-1 for the CAF1 and CAF2 trials, respectively. This was significantly higher (P < 0.0001) than the CON level which was 0.97 (SEM 0.19) mmol.l-1. Respiratory exchange ratio (R) values became significantly lower (P < 0.05) in CAF1 and CAF2 compared to CON at the onset of exercise and continued to decrease during the activity. Throughout the recovery period, R values were significantly lower for both caffeine trials compared to CON. The results of this study would suggest that caffeine is useful in significantly increasing metabolic rate above normal levels in untrained women during, as well as after, exercising at 55% VO2max. PMID- 1425654 TI - Effect of moderate exercise on rat T-cells. AB - The aim of this study was a detailed examination of the effects of moderate exercise on T-cells in adult male Wistar rats. The T-cell populations were compared in sedentary rats (C, n = 5) and in rats trained for 4 weeks on a treadmill (30-60 min.day-1, 6 days.week-1, 20-30 m.min-1) and sacrificed at rest (T-rest, n = 5). In the T-rest rats, there were higher percentages of CD4+CD8-, CD4-CD8+ and CD4-CD8- thymocytes (P < 0.05, P < 0.05 and P < 0.01 respectively) and of CD4-CD8+ splenocytes (P < 0.01), and a lower percentage of CD4-CD8+ cells in the lymph nodes (P < 0.01). Compared with T-rest or C rats, trained rats (n = 5) or untrained rats (n = 5) sacrificed immediately after a running session (60 min, 30 m.min-1) had a higher percentage of mononucleated cells CD4+CD8- in the blood (P < 0.05 and P < 0.01). Lastly, compared with C rats, rats (n = 5) sacrificed immediately after their 5th day of training (30-60 min.day-1) presented a higher total splenocyte population (P < 0.05) and greater in vitro production of T-cell growth factor (interleukin 2 + Interleukin 4) by splenocytes in response to a mitogen (P < 0.01). These results would indicate that moderate endurance training modifies the cellular composition of lymphoid organs, without impairing the in vitro functions of T-cells. PMID- 1425655 TI - Effects on efficiency in repetitive lifting of load and frequency combinations at a constant total power output. AB - Boxes were lifted and lowered repetitively at three different combinations of load and frequency. These combinations were chosen such that the total mechanical power generated was constant. Effects of the varying load or frequency conditions (but constant total mechanical power) on the rate of energy expenditure (M) and on the mechanical efficiency (ME) were measured. Mechanical power was determined from film analysis and separated into external power (generated to lift the load) and internal power (to raise the lifter's body mass). The M was determined from oxygen consumption measurements. The ME was calculated in two ways, depending on the definition of mechanical power, including either the external power only (MEext) or the total power output (MEtot). Despite a constant total mechanical power, M increased at higher loads and lower frequencies. This might be explained by the increasing isometric force required in postural and load control. The M increase resulted in a decrease of MEtot. However, at higher loads and lower frequencies MEext increased, indicating that more external work can be done at the same energy costs at higher loads or lower frequencies, which could be of interest from the point of view of occupational physiology. It would seem that at higher loads or lower frequencies the increased costs for isometric muscle action do not outweigh the benefit of raising the body less frequently. Furthermore, it was found that the MEext in lifting was much lower than the values reported for other kinds of activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425656 TI - The effect of shuttle test protocol and the resulting lactacidaemia on maximal velocity and maximal oxygen uptake during the shuttle exercise test. AB - The purpose of this study was to investigate the influence of the shuttle test protocol (20-MST) and the resulting lactacidaemia on maximal velocity (Vmax) and maximal oxygen uptake (VO2max). Firstly, three randomly assigned tests to exhaustion were performed by 12 subjects: the treadmill test, the 20-MST, and a continuous running track test using the same prerecorded 1-min protocol as in the 20-MST (T1). One week later, subjects performed another track test, which was conducted up to the same level of effort as attained during the 20-MST (T2). For each test, Vmax, VO2max, lactate concentration at rest and during recovery, maximal heart rate, and distance covered were determined. The results indicated that the 20-MST underestimated Vmax; only T1 satisfactorily assessed Vmax (F = 15.49, P < 0.001). At the same level of effort, the peak blood lactate concentration (t = 2.7, P < 0.02) and VO2max (t = 11.35, P < 0.001) values were higher for the shuttle than for the continuous protocol. It was concluded that Vmax was limited by the running backwards and forwards in the protocol of the shuttle test. The higher values of peak blood lactate concentration and its earlier appearance obtained for the shuttle may have been one of the limiting factors of Vmax. However, the higher values of VO2max obtained for the 20-MST were most likely due to a combination of the relative hyperlactacidaemia and the biomechanical complexities required for this type of protocol. PMID- 1425657 TI - Changes in ventilation in response to ramp changes in treadmill exercise load. AB - These experiments examined the changes in ventilation during a 40-s ramp increase in exercise load, produced by increasing either the speed of the treadmill or the grade, to equivalent end-points of oxygen uptake. Six subjects underwent five trials each for grade and speed, while ventilation was monitored breath-by breath. For each subject, ventilation versus time for all five of the speed trials was plotted on a single graph and fitted by linear regression. The data for the grade trials were similarly treated. For all subjects, the slope of the regression line for the speed plots was found to be significantly (P < 0.05) greater than that for the grade plots. We concluded that these experimental results support the hypothesis that the neural drive to ventilation persists as exercise continues and is proportionately related to the frequency of limb movement. PMID- 1425658 TI - The asparaginyl-tRNA synthetase gene encodes one of the complementing factors for thermosensitive translation in the Escherichia coli mutant strain, N4316. AB - Escherichia coli strain N4316 is a mutant that exhibits temperature-sensitive growth at 43 degrees C and temperature-sensitive translation in vivo and in vitro. Extracts of the mutant produce an aberrant pattern of translation products of MS2 bacteriophage RNA. Previous work has shown that a protein, called 'rescue', isolated from the parental strain partly corrects the defective translation in vitro. Here we report the purification to homogeneity of a second factor from ribosomal eluates of the wild-type parental strain; the purified protein is a homodimer of 54 kDa. The partial sequence of the second protein was determined, and a recombinant plasmid was isolated based on its ability to complement the temperature-sensitive growth phenotype of the mutant at the non permissive temperatures. The cloned gene was sequenced, mapped to the 20.9-min region of the E. coli chromosome and shown to code for a 466-amino-acid protein with a molecular mass of 52 kDa. Analysis of the DNA sequence and the correspondence to that of the partial protein sequence has identified the complementing factor as asparaginyl-tRNA synthetase. Marker rescue experiments indicate that the asnS mutation in N4316 resides within the motif 2 domain of the synthetase. A potential role of this synthetase in restoring normal protein synthesis with respect to ribosomal frameshifting, read-through of nonsense codons and protein copy number is discussed. PMID- 1425659 TI - Functional analysis of alternatively spliced transcripts of the human histidine decarboxylase gene and its expression in human tissues and basophilic leukemia cells. AB - L-Histidine decarboxylase (HisDC) is the enzyme catalyzing the formation of histamine from L-histidine. HisDC activity is expressed specifically in mast cells/basophils, endocrine cells in stomach, and histaminergic neurons in brain. As a first step in the analysis of the regulation of HisDC gene expression, we have cloned the cDNA coding for HisDC from a cDNA library of a human basophilic leukemia cell line, KU-812-F. We identified two types of HisDC cDNA, representing the 2.4-kb and 3.4-kb HisDC mRNA constitutively expressed in these cells. Sequence analysis of these cDNA revealed that the 3.4-kb mRNA contains the insert sequence of 824 bases and suggests that both 2.4-kb and 3.4-kb mRNA may represent the alternatively spliced transcripts of the HisDC gene. Using expression plasmids containing a cDNA for each HisDC mRNA, we analyzed the function of possible HisDC isoforms. We show that only the 2.4-kb mRNA encodes functional HisDC and is expressed in human brain and lung. However, we were unable to detect the 3.4-kb mRNA in these tissues. Thus, the 3.4-kb mRNA may be generated by KU 812-F cell-specific splicing of the HisDC gene transcripts. Furthermore, we demonstrated the increase in the level of 2.4-kb HisDC mRNA and HisDC activity in KU-812-F cells following treatment with phorbol 12-myristate 13-acetate. PMID- 1425660 TI - Concerted activities of the RNA recognition and the glycine-rich C-terminal domains of nucleolin are required for efficient complex formation with pre ribosomal RNA. AB - Nucleolin is an abundant nucleolar protein which is involved in the early stages of ribosome assembly. The central 40-kDa domain of nucleolin comprises four RNA recognition motifs (RRM) which are presumed to be involved in specific interactions with pre-rRNA. In order to examine in detail the role of this central domain and the contribution of the N-terminal and C-terminal domains of nucleolin to RNA binding, we have used an Escherichia coli expression system to synthezise polypeptides corresponding to various combinations of the three domains and their subdomains. By means of an in-vitro binding assay and a synthetic RNA corresponding to a specific recognition site in pre-rRNA we have been able to demonstrate conclusively that the central 40-kDa domain is indeed responsible for the specificity of RNA recognition and that the N-terminal domain can be removed without affecting RNA binding. Most interestingly, it appears that the C-terminal 10-kDa domain, which is rich in glycine and arginine residues, is essential for efficient binding of nucleolin to RNA, but does not itself contribute to the specificity of the interaction. Circular dichroic spectroscopic probing of the RNA component shows that the C-terminal domain significantly modifies the RNA-binding properties of the central RRM core. Finally, infrared spectroscopic studies reveal that the central 40-kDa domain is structured in alpha helices and beta sheets and that the interaction with the specific pre-rRNA site induces subtle changes in the beta sheet conformation. PMID- 1425661 TI - Effect of heat shock on expression of proteins not involved in the heat-shock regulon. AB - The effect of heat shock on the expression of some genes of Escherichia coli was tested. To avoid side effects, promoters of the genes were fused to lacZ and their expression measured by the level of beta-galactosidase. The results show that expression of umuC, recA and polB, after induction of the SOS response, was somewhat higher in the heat-shocked than in the non-shocked cells, whereas expression of ada, alkB and alkA genes, after induction of the adaptive response, was about the same. Unexpectedly, it was found that expression of lacZ from its own promoter was drastically lowered in the heat-shocked cells. This effect, however, seems not to be dependent on the induction of heat-shock proteins. PMID- 1425662 TI - Localization and identification of actin structures involved in the filamin-actin interaction. AB - The interface between gizzard filamin and skeletal muscle actin was located on the actin monomer. Conserved sequences 105-120 and 360-372, in the actin subdomain 1 near the myosin binding sites, were involved in this interaction. The corresponding peptides for these sequences were each found to bind filamin and compete in the actin-filamin interaction. When these two peptides were used together in the presence of filamin and filamentous actin, they dissociated sedimentable complexes formed by these two proteins. PMID- 1425663 TI - Ovohemerythrin, a major 14-kDa yolk protein distinct from vitellogenin in leech. AB - A 14-kDa protein was identified as a major component of mature oocytes of the leech Theromyzon tessulatum. This protein was, like vitellin, detected in the content of yolk granules and was purified by gel-permeation and ion-exchange chromatography. The yolk protein corresponded to an iron-binding protein which exists in a monomeric unglycosylated form and had no similarities to vitellin. However, a strong resemblance between this protein and sipunculid hemerythrin, a non-heme iron-binding protein, was observed on the basis of its characteristics including molecular mass, iron content, ultraviolet/visible spectrum, amino acid composition and N-terminal sequence. These similarities with hemerythrin and the accumulation of the protein in the oocyte justify the name ovohemerythrin given to the molecule. A coelomic-fluid protein immunologically related to ovohemerythrin was detected in vitellogenic animals. The protein was purified with the chromatographic procedure used to isolate ovohemerythrin from oocytes and was found to be similar to the oocyte protein. This circulating ovohemerythrin was present in large amounts in the coelomic fluid while gametogenesis is in progress, i.e. after the third and last blood meal of the animal (stage 3), except at the time of oocyte enlargement when its concentration decreases dramatically. However, in contrast to vitellogenin, which is detected specifically in the coelomic fluid of leeches at stage 3, circulating ovohemerythrin is also observed after the first (stage 1) and second (stage 2) blood meal. This observation suggests a more complex function for ovohemerythrin than being merely a yolk nutrient for the embryo. PMID- 1425664 TI - Recombinant laminin B1 chains exhibit intact short-arm domains but do not form oligomeric molecules. AB - The human laminin B1 chain has been produced in the baculovirus expression system in sufficient amounts for biochemical and functional studies. A full-length cDNA, which was constructed of four partially overlapping clones and verified by in vitro transcription and translation to be functional, was cloned into the transfer vector pVL1392 behind the polyhedrin promoter. The recombinant construct was incorporated by in vivo homologous recombination into the genome of the wild type baculovirus, Autographa californica nuclear polyhedrosis virus. Infection of Spodoptera frugiperda cells (Sf9) with the recombinant virus resulted in the expression of the recombinant B1 chain (recB1) in these insect cells. The recB1 was found to be synthesized in two forms with apparent molecular masses of 220 kDa and 200 kDa. The 220-kDa form is an N-glycosylated form of recB1, because it was not present in cultures containing tunicamycin, an inhibitor of N-linked glycosylation. The recB1 accumulated inside the cell and only a small portion of it was secreted into the culture medium. Thus purification had to be started from the cell extract in order to obtain reasonable amounts of the protein. About 500 micrograms was obtained from a 500-ml culture with three steps of chromatography, concavalin A, DEAE-Sepharose and Mono Q anion-exchange chromatography. Only the glycosylated form was purified. The recB1 was found to be sensitive to degradation during the purification, because two proteolytic forms of about 180 kDa were present in every preparation. The accumulation of recB1 inside the cell was possibly due to the lack of correct assembly. Electron microscopy studies showed that the short arm part had a native or near-native structure, but the C terminal heptad repeat domain had not folded correctly and did not exist in an alpha-helical structure, as it does in native laminin. Electron microscopy and cross-linking studies further revealed that recB1 was a monomeric protein. It was also shown to be unable to oligomerize in vitro, suggesting that the B1 chain is not designed to form homo-oligomers. Finally, cell attachment assays were carried out, but the native recB1 appeared to be inactive in these assays. PMID- 1425665 TI - Heme-pocket-hydration change during the inactivation of cytochrome P-450camphor by hydrostatic pressure. AB - Hydrostatic pressure has been used to convert cytochrome P-450camphor to cytochrome P-420. The latter is an inactivated but soluble and undenaturated form of cytochrome P-450camphor. Using camphor analogues as probes of the active site we show that the inactivation volume change is directly correlated to the initial degree of hydration of the heme pocket. The values range between -73 ml/mol and 197 ml/mol [Di Primo, C., Hui Bon Hoa, G., Douzou, P. & Sligar, S. G. (1990) Eur. J. Biochem. 193, 383-386] for a totally hydrated (substrate-free, low-spin, six coordinated heme iron) and a non-hydrated (camphor-bound, high-spin, five coordinated heme iron) heme pocket. These results suggest that the larger value, 197 ml/mol, for the inactivation volume change is due to a hydration change of the heme pocket resulting from the displacement of the substrate during the compression and the subsequent entrance of water molecules. Similarly, the stability of the protein against compression is correlated with water accessibility to the active site. Increase in substrate mobility by loss of specific interactions with both regions of well defined secondary structure of cytochrome P-450camphor results in an increase of water accessibility and decrease of stability. Thus for camphor and adamantanone which strongly interact with the protein and exclude water from the active site [Poulos, T. L., Finzel, B. C. & Howard, A. J. (1987) J. Mol. Biol. 195, 687-700; Raag, R. & Poulos, T. L. (1989) Biochemistry 28, 917-922] the increase in stability compared to the free protein is roughly 30 kJ/mol at 20 degrees C. With smaller substrates such as norcamphor, which loosely fits into the active site and does not completely exclude water [Raag, R. & Poulos, T. L. (1989) Biochemistry 28, 917-922], the increase in stability is only 7 kJ/mol. Finally these results suggest that cytochrome P-420 induced by hydrostatic pressure is a unique form where the active site is hydrated and camphor is displaced from its binding site. PMID- 1425666 TI - Proteolytic cleavage by neutrophil elastase converts inactive storage proforms to antibacterial bactenecins. AB - Bac5 and Bac7, antibiotics of the bactenecin (proline/arginine-rich peptide) family, are stored as proforms in the large granules of bovine neutrophils [Zanetti, M., Litteri, L., Gennaro, R., Horstmann, H. and Romeo, D. (1990) J. Cell Biol. 111, 1363-1371]. These proforms have been purified to homogeneity from granule extracts by immunoaffinity and reverse-phase chromatography. While mature bactenecins efficiently kill Escherichia coli, Klebsiella pneumoniae and Salmonella typhimurium with minimal inhibitory concentrations of 6-12 micrograms/ml, proBac5 and proBac7 do not affect the growth of the same microorganisms, even at 500 micrograms/ml. Previous investigations have suggested that the conversion of probactenecins into mature antimicrobial peptides is catalyzed by a neutral serine protease stored in the azurophil granules. Purified proBac5 and proBac7 were thus treated with elastase, cathepsin G or proteinase 3, which constitute the pool of neutral serine proteases of the azurophils, and the reaction products were identified by Western blot analysis, mass spectrometry, and N-terminal sequence analysis. Of the three proteases, only elastase is able to catalyze the stepwise cleavage of probactenecins into the corresponding mature peptides, which have the same mass, N-terminal sequence and antibiotic activity of authentic Bac5 and Bac7. These results point to the importance of cooperation between azurophils and large granules in mounting a defense reaction. PMID- 1425667 TI - Substrate specificity and properties of the aryl-alcohol oxidase from the ligninolytic fungus Pleurotus eryngii. AB - The production in a 5-1 fermenter of the extracellular enzymes laccase and aryl alcohol oxidase by the fungus Pleurotus eryngii was studied. The latter enzyme has been purified 50-fold by Sephacryl S-200 and Mono Q chromatography. Purified aryl-alcohol oxidase is a unique flavoprotein with 15% carbohydrate content, a molecular mass of 72.6 kDa (SDS/PAGE) and a pI of 3.9. The enzyme presents wide specificity, showing activity on benzyl, cinnamyl, naphthyl and aliphatic unsaturated alcohols. Neither activity nor inhibition of veratryl alcohol oxidation was found with saturated alcohols, but competitive inhibition was produced by aromatic compounds which were not aryl-alcohol oxidase substrates, such as phenol or 3-phenyl-1-propanol. From these results, it was apparent that a double bond conjugated with a primary alcohol is necessary for substrate recognition by aryl-alcohol oxidase, and that activity is increased by the presence of additional conjugated double bonds and electron donor groups. Both affinity and maximal velocity during enzymic oxidation of methoxybenzyl alcohols were affected in a similar way by ring substituents, increasing from benzyl alcohol (Km = 0.84 mM, Vmax = 52 U/mg) to 4-methoxybenzyl alcohol (Km = 0.04 mM, Vmax = 208 U/mg). Aryl-alcohol oxidase presents also a low oxidase activity with aromatic aldehydes, but the highest activity was found in the presence of electron-withdrawing groups. PMID- 1425668 TI - Iron release from ferrisiderophores. A multi-step mechanism involving a NADH/FMN oxidoreductase and a chemical reduction by FMNH2. AB - Release of iron from various ferrisiderophores (ferripyoverdines, ferrioxamines B and E, ferricrocin, ferrichrome A, ferrienterobactin and its analog ferric N,N',N''-tri(1,3,5-Tris) 2,3-dihydroxybenzoylaminomethylbenzene) was obtained through an enzymic reduction of iron, involving NADH, FMN and the ferripyoverdine reductase of Pseudomonas aeruginosa PAO1. The iron released from the same complexes was also obtained through chemical reduction of iron involving FMNH2. Evidence is given that the enzymic process acts through a FMNH2 reduction; the P. aeruginosa enzyme, purified according to its ferripyoverdine-reductase activity [Halle, F. & Meyer, J. M., Eur. J. Biochem. 209, 613-620], functions as a NADH:FMN oxidoreductase, the FMNH2 produced being able to chemically reduce the iron complexed by siderophores. The general occurrence of such a multi-step mechanism, which denies the existence of specific ferrisiderophore reductases, is discussed. PMID- 1425669 TI - Use of serine-protease inhibitors as probes for the different proteolytic activities of the rat liver multicatalytic proteinase complex. AB - The multicatalytic proteinase (MCP) complex catalyses cleavage of bonds on the carboxy-group side of basic, hydrophobic or acidic amino acid residues. Originally, it was proposed that the complex contained three distinct types of catalytic component. MCP from rat liver has been assayed for so-called trypsin like activity with Boc-Leu-Ser-Thr-Arg-NH-Mec (Mec, 4-methylcoumarin; Boc, t butoxycarbonyl), for chymotrypsin-like activity with Ala-Ala-Phe-NH-Mec and Suc Leu-Leu-Val-Tyr-NH-MEc (Suc, succinyl), and peptidyl-glutamylpeptide hydrolase activity with Cbz-Leu-Leu-Glu-Nap (Nap, naphthylamide; Cbz, benzyloxycarbonyl). Results of these studies suggest that as many as five distinct components can be distinguished, one for the trypsin-like activity and two for each of the others. The activities were tested with a variety of serine-protease inhibitors, and other novel effectors have also been identified. The two most effective inhibitors were 4-(2-amino-ethyl)benzenesulphonyl fluoride, which selectivity inactivates the trypsin-like activity, and 3,4-dichloroisocoumarin which inhibits chymotrypsin-like activity and the second, cooperative component [Djaballah, H. & Rivett, A. J. (1992) Biochemistry 31, 4133-4141] of peptidylglutamylpeptide hydrolase activity. The three activities inhibited by 3,4-dichloroisocoumarin can easily be distinguished by the effects of chymostatin analogues, diisopropylfluorophosphate, guanidine/HCl and casein. The results support the view that the enzyme is a novel type of serine protease and suggest that it may contain at least five distinct catalytic components. Marked differences in the reactivities of the different catalytic sites with different reagents can be used to distinguish between them. PMID- 1425670 TI - Characterization and molecular cloning of neurotoxic phospholipases A2 from Taiwan viper (Vipera russelli formosensis). AB - Two phospholipases A2 (PLA2s), designated as RV-4 and RV-7 were purified from venom of the Taiwan Russell's viper (Vipera russelli formosensis) by gel filtration and reverse-phase HPLC. Their primary structures were solved by both protein sequencing and cDNA cloning and sequencing. The cDNA synthesized was amplified by the polymerase-chain reaction using a pair of synthetic oligonucleotide primers corresponding to the N- and the C-terminal flanking regions of the enzymes. The deduced amino acid sequences of RV-4 and RV-7 were 92% identical to those of the vipoxin and vipoxin inhibitor, respectively, from the Bulgarian Vipera a. ammodytes. RV-4 itself was neurotoxic, whereas RV-7 had much lower enzymatic activity and was not toxic. The low enzymatic activity of RV 7 may be attributed to five acidic residues at positions 7, 17, 59, 114 and 119, which presumably impair its binding to aggregated lipid substrates. Based on the sequence comparison among all the known group II PLA2s, residues 6, 12, 76-81, and 119-125 were identified as important for the neurotoxicity. RV-4 and RV-7 exist in the crude venom as heterodimers, which were again formed by mixing together the HPLC-purified RV-4 and RV-7. Moreover, RV-7 inhibited the enzymatic activity of RV-4 in vitro but potentiated its lethal potency and neurotoxicity. It is suggested that RV-7 may facilitate the specific binding of RV-4 to its presynaptic binding sites, probably by preventing its non-specific adsorption. PMID- 1425671 TI - Purification and properties of Aspergillus niger beta-glucosidase. AB - Beta-glucosidase was purified from a crude cellulase preparation from Aspergillus niger by affinity chromatography on a methacrylamide-N-methylene-bis methacrylamide copolymer bearing cellobiamine. The purified enzyme was a dimer with an isoelectric point of 4.0. The molecular mass of the enzyme was estimated to be 240 kDa by gel-permeation chromatography. The enzyme hydrolyzed specifically beta-glucosidic bonds and catalyzed transglucosylation of the beta glucosyl group of cellobiose to yield 4-O-beta-gentiobiosylglucose in the presence of organic solvents or under neutral conditions. PMID- 1425672 TI - 1,4-Diamino-2-butyne as the mechanism-based pea diamine oxidase inhibitor. AB - 1,4-Diamino-2-butyne is a mechanism-based inhibitor of diamine oxidase (EC 1.4.3.6) from pea cotyledons. It shows saturation kinetics Km = 1 mM like a substrate, but its interaction leads to time-dependent loss of enzyme activity which is not restored by gel filtration. The substrate 1,4-diaminobutane and the competitive inhibitor 1,4-diamino-2-butanone protect the enzyme against inactivation. Changes in the enzyme electronic spectra with 1,4-diamino-2-butyne were found. The mechanism of the interaction involves an intermediate aminoallenic compound, which is formed with covalent bound pyrrole in the reaction of the nucleophile with the enzyme. The presence of a pyrrole in the inactivated enzyme was confirmed by reaction with Ehrlich's reagent. The kinetic data obtained in this study indicate that 1,4-diamino-2-butyne is a mechanism based inactivator with number of turnovers, r = 17 and characteristic constants K' = 0.32 mM and k(in) = 4.89 min-1. PMID- 1425674 TI - Secondary and tertiary structures involving chondroitin and chondroitin sulphates in solution, investigated by rotary shadowing/electron microscopy and computer simulation. AB - Rotary shadowing/electron microscopy of chondroitin 6-sulphate (CS6) and 4 sulphate (CS4) showed that the former, but not the latter, aggregated to mesh works. Preparations made from salt (ammonium acetate) solutions showed enhanced aggregation. Computer modelling, using molecular mechanics and dynamics, was applied to secondary structures (twofold helices) derived from NMR studies, to determine geometric and energetic constraints on duplex and higher-aggregate formation. The calculations suggested that chondroitin, CS6 and undersulphated CS4 could form duplexes, while CS4 could not, thus bridging the gap between atomic dimensions (NMR) and high polymer scale (electron microscopy). Calculations suggested that water structure helped to stabilise the twofold helix. It is proposed that the twofold helical, flat, tape-like molecules aggregate via hydrophobic bonding between the very extensive hydrophobic patches (9 CH units) repeated on alternating sides of the polymers. The negative charge of the polyanions opposes aggregate formation. Calculations showed that duplexes were formed with decreasing stability as the charge density increased, and as the charge was concentrated towards the centre line of the polymer (i.e. in CS4). The unsulphated polymer chondroitin could form duplexes and higher aggregates as readily as hyaluronan. Hyaluronan was calculated to form stable heteroduplexes with CS6 and CS4. The frequency and positioning of the sulphate-ester group within the polymer thus determines whether the molecule participates in duplex formation. PMID- 1425673 TI - Desaturation of polyunsaturated fatty acids in Mucor circinelloides and the involvement of a novel membrane-bound malic enzyme. AB - 1. The component fatty acids of the endogenous phospholipids of microsomal preparations of Mucor, when shaken at 30 degrees C, increased in both chain length and in degree of unsaturation. The net effect was the production of gamma linolenic acid which, over 2 h, increased from 17% to 32% of total fatty acids present. No further significant changes occurred after this time. 2. The major site for desaturation/elongation reactions was at the sn-2 position of PtdIns. PtdCho and PtdEtn were not implicated. 3. Of numerous metabolites and cofactors added to the microsomes, only malate could prolong the elongation/desaturation reactions for up to 6 h. This effect was shown to be due to a membrane-associated malic enzyme [malate dehydrogenase (decarboxylating) NADP+] with the NADPH produced being used in fatty-acid desaturation. 4. Kinetic analysis of cytosolic and microsomal enzymes [both in 0.1% (mass/vol.) Chaps] could not distinguish between them. However, when the microsomal malic enzyme was dialysed to remove Chaps, it lost 90% of activity, although the cytosolic malic enzyme lost only 20% activity. 5. The structural analogue of malate, tartronic acid, which is an inhibitor of malic enzyme, also inhibited the malate-induced stimulation of fatty acyl group desaturation and elongation in the microsomal membranes. 6. It is concluded that two distinct malic enzymes exist, one soluble and one membrane bound, with similar active sites. Both have different roles in the production of NADPH, for lipid metabolism. The former will produce NADPH for fatty-acid biosynthesis whilst the latter produces NADPH for fatty-acid desaturation. PMID- 1425675 TI - The mechanism of stimulation of MgATPase activity of chloroplast F1-ATPase by non catalytic adenine-nucleotide binding. Acceleration of the ATP-dependent release of inhibitory ADP from a catalytic site. AB - The presence of ATP at non-catalytic sites of the chloroplast F1-ATPase (CF1) eliminates a considerable lag in onset of enzyme activity that otherwise occurs in the presence of bicarbonate [Milgrom, Y. M., Ehler, L. & Boyer, P. D. (1991) J. Biol. Chem. 266, 11551-11558]. Sulfite is known to be much more effective than bicarbonate in stimulating ATPase activity CF1. Results reported here show that when assayed in the presence of sulfite, CF1, with some non-catalytic sites empty or filled with GT(D)P, is able to hydrolyze both ATP and GTP. Thus, the presence of adenine nucleotides at non-catalytic sites is not necessary for catalytic turnover of CF1. However, even though CF1 with empty non-catalytic sites shows a significant initial activity, the prior binding of adenine nucleotides at non catalytic site(s) results in further activation of MgATPase and MgGTPase activities, even at relatively high sulfite and substrate concentrations. Although extensive activation of CF1 results from the presence of sulfite, with or without nucleotide binding at non-catalytic sites, the Km remains constant, at about 50 microM for MgATP and 400 microM for MgGTP. The results obtained show that the ATPase activity of CF1 is determined by the fraction of the active enzyme. The inactive CF1.ADP.Mg2+ formed during MgATP hydrolysis can be rapidly trapped by azide to provide a measure of the fraction of inactive enzyme. Increasing the concentration of sulfite increases the fraction of active CF1 in the assay medium. Measurements with radioactively labeled nucleotides show that the presence of ATP at non-catalytic sites promotes the ATP-dependent release of inhibitory ADP from a catalytic site. The activating effect of ATP binding at non catalytic sites results from increasing the portion of CF1 in an active state during steady-state ATP hydrolysis. PMID- 1425676 TI - Mechanism of the inhibition of cell growth by N1,N12-bis(ethyl)spermine. AB - The mechanism of the antiproliferation effect of N1,N12-bis(ethyl)spermine (BESPM) was studied in detail using mouse FM3A cells, since this polyamine analogue mimics the functions of spermine in several aspects [Igarashi, K., Kashiwagi, K., Fukuchi, J., Isobe, Y., Otomo, S. & Shirahata, A. (1990) Biochem. Biophys. Res. Commun. 172, 715-720]. Our results indicate that not only the decrease in sperimine and spermine caused by BESPM but also its accumulation play important roles on the inhibition of cell growth by BESPM, since BESPM accumulated in cells at a concentration fivefold that of spermidine in control cells. In comparison with the polaymine-deficient cells caused by alpha difluoromethylornithine, an inhibitor of ornithine decarboxylase, and ethylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, the behavior of polyamine-deficient cells caused by BESPM was different as follows: the inhibition of cell growth by BESPM was not abrogated by spermine or spermidine; polyamine uptake, which is stimulated during polyamine deficiency, was greatly inhibited, while spermidine/spermine N1-acetyltransferase activity, which is inhibited during polyamine deficiency, was enhanced in BESPM treated cells; thymidine kinase activity did not decrease in BESPM-treated cells; inhibition of cell growth and macromolecule synthesis by BESPM correlated with the swelling of mitochondria and the decrease in ATP content; BESPM caused cell death when incubated together for several days. The role of BESPM accumulation on inhibition of cell growth is discussed. PMID- 1425677 TI - Purification of human leukotriene C4 synthase from dimethylsulfoxide differentiated U937 cells. AB - Human leukotriene C4 (LTC4) synthase was purified > 10000-fold from dimethylsulfoxide-differentiated U937 cells. Steps included: (a) solubilization of membrane-bound LTC4 synthase from microsomal membranes by the anionic detergent taurocholate; (b) successive anion-exchange chromatography steps in the presence of taurocholate plus Triton X-100 (primary anion exchange) then taurocholate plus n-octyl glucoside (secondary anion exchange); and (c) LTC2 affinity chromatography on a matrix that was constructed by first biotinylating synthetic LTC2 then immobilizing the biotinylated LTC2 on streptavidin agarose. The purification of human LTC4 synthase was enabled by the finding that LTC4 synthase activity in preparations enriched > 500-fold was absolutely dependent on the presence in LTC4 synthase incubation mixtures of divalent cations (specifically Mg2+) and phospholipids (specifically phosphatidylcholine), and that reduced glutathione, which was required at 2-4 mM for stabilization of LTC4 synthase, irreversibly inactivated the enzyme when present at > or = 5 mM during freeze/thaw cycles. The > 10000-fold purified LTC4 synthase preparation was comprised of three polypeptides having molecular masses of 37.1, 24.5 and 18.0 kDa. An 18-kDa polypeptide in both microsomal membranes and in the LTC2-affinity purified fraction was specifically labelled by a radioiodinated LTC4 photoaffinity probe (azido 125I-LTC4). The Km values in the LTC2-affinity purified preparation for reduced glutathione and LTA4 were 1.83 mM and 19.6 microM (respectively), closely resembling the Km values in isolated human blood monocytes. The Vmax of LTC2-affinity purified LTC4 synthase was 2-4 mumol LTC4 formed .min-1 x mg-1. PMID- 1425678 TI - Cytosolic and intranuclear calcium signals in rat basophilic leukemia cells as revealed by a confocal fluorescence microscope. AB - A confocal fluorescence microscope with an argon-ion laser (488 nm) and a He-Cd laser (325 nm) was used to study spatial heterogeneity of the calcium signals in rat basophilic leukemia 2H3 cloned cell line (RBL-2H3). After stimulation with antigen (2,4-dinitrophenol-conjugated bovine serum albumin), fluo-3-fluorescence intensities increased in individual RBL-2H3 cells with different lag times. Time dependent profiles of the fluo-3-fluorescence intensities resembled closely the patterns of the sequential fluorescence-ratio images of fura-2, which were used to measure the intracellular free-calcium concentration ([Ca2+]i) in individual RBL-2H3 cells using a conventional fluorescence microscope. The present results obtained using the confocal fluorescence microscope showed spatial heterogeneities of fluo-3-fluorescence intensities, suggesting the existence of spatial heterogeneity of [Ca2+]i in RBL-2H3 cells. That is, the results showed that calcium signals first occurred transiently at pseudopodia in RBL-2H3 cells, then the signals transferred to the central parts of the cells. In addition, from the fluorescence images of co-loaded Hoechst 33342 (bisbenzimide H 33342, a DNA specific probe) which were produced by excitation with a He-Cd laser, it was found that the fluorescence images of the nucleus were quite similar to those of the calcium signals mentioned above. This suggested that the receptor-mediated calcium signals were transferred not only to the cytoplasm but also to the nucleus. PMID- 1425679 TI - Characterization of tryptophan phosphorescence of aspartate aminotransferase from Escherichia coli. AB - The Trp phosphorescence spectrum, intensity and decay kinetics of apo-aspartate aminotransferase, pyridoxamine-5P-aspartate-aminotransferase and pyridoxal-5P aspartate aminotransferase were measured over a temperature range 160-273 K. The fine structure of the phosphorescence spectra in low-temperature glasses, with 0 0 vibrational bands centered at 408, 415 and 417 nm, for both apoenzyme and pyridoxamine-5P-enzyme reveals a marked heterogeneity of the chromophore environments. Only for the pyridoxal-5P form of the enzyme is the triplet emission strongly quenched and, in this case, the spectrum displays a unique 0-0 vibrational band centered at 415 nm. Concomitant to quenching, there is Trp sensitized delayed fluorescence of the Schiff base, an indication that quenching of the excited triplet state is due, at least in part, to a process of triplet singlet energy transfer to the ketoenamine tautomer. All three forms of the enzyme are phosphorescent for temperatures up to 273 K. However, across the glass transition temperature the pyridoxal-5P enzyme shows a decrease in lifetime normalized phosphorescence intensity, a thermal quenching that reduces even further the number of phosphorescing residues at ambient temperature. In fluid solution, the triplet decay is nonexponential and multiple lifetimes stress the heterogeneity in dynamical structure of the chromophores' sites. For the pyridoxal-5P enzyme, where only one or at most two residues are phosphorescent at 273 K, the nonexponential nature of the decay implies the presence of different conformers of the protein not interconverting in the millisecond time scale. PMID- 1425680 TI - Solution conformation of human neuropeptide Y by 1H nuclear magnetic resonance and restrained molecular dynamics. AB - The solution structure of human neuropeptide Y has been solved by conventional two-dimensional NMR techniques followed by distance-geometry and molecular dynamics methods. The conformation obtained is composed of two short contiguous alpha-helices comprising residues 15-26 and 28-35, linked by a hinge inducing a 100 degree angle. The first helix (15-26) is connected to a polyproline stretch (residues 1-10) by a tight hairpin (residues 11-14). The helices and the polyproline stretch are packed together by hydrophobic interactions. This structure is related to that of the homologous avian pancreatic polypeptide and bovine pancreatic polypeptide. The C- and N-terminii, known to be involved in the biological activity for respectively the receptor binding and activation, are close together in space. The side chains of residues Arg33, Arg35 and Tyr36 on the one hand, and Tyr1 and Pro2 on the other, form a continuous solvent-exposed surface of 4.9 mm2 which is supposed to interact with the receptor for neuropeptide Y. PMID- 1425681 TI - Molecular basis of low-temperature sensitivity in pig hemoglobins. AB - It has been generally assumed that mammals have blood with a greater temperature sensitivity than ectothermic organisms. Recent results have shown that in some species of mammals, Hb displays a value of overall oxygenation enthalpy (delta H) much less exothermic than that observed for most mammalian hemoglobins, including human adult Hb. In this respect, a very interesting case is represented by porcine blood which shows a modest effect of temperature, the temperature coefficient of its oxygen-dissociation curve being significantly lower than that of human blood. Here we report a detailed functional characterization of pig Hb, which, interpreted on the basis of the amino acid sequence of the alpha and beta chains of the molecule, sheds some light on the molecular basis of the phenomenon. PMID- 1425682 TI - Stopped-flow fluorescence and steady-state kinetic studies of ligand-binding reactions of glucoamylase from Aspergillus niger. AB - The presteady-state and steady-state kinetics of the binding and hydrolysis of substrates, maltose and isomaltose, and the transition-state analogue, gluconolactone, by glucoamylase from Aspergillus niger were investigated using initial-rate, stopped-flow and steady-state methods. The change in the intrinsic fluorescence of the enzyme was monitored. Distinct mechanistic differences were observed in the interaction of the enzyme with maltose compared to isomaltose. Hydrolysis of maltose requires a three-step mechanism, whereas that of isomaltose involves at least one additional step. The rates of an observed conformational change, which is the second discernible step of the reactions, clearly show a tighter binding of maltose compared to isomaltose, probably because the reverse rate constants differ. Compared to the non-enzymic hydrolysis the transition state stabilization energy of glucoamylase is approximately -66 kJ/mol with maltose and only -14 kJ/mol with isomaltose. Kinetic analysis of the binding of the inhibitor, gluconolactone, implies that independent interactions of two molecules occur. One of these, apparently, is a simple, fast association reaction in which gluconolactone is weakly bound. The other resembles binding of maltose, involving a fast association followed by a conformational change. Based on the results obtained, we propose new reaction mechanisms for Aspergillus glucoamylase. PMID- 1425683 TI - Dissociation of F-actin induced by hydrostatic pressure. AB - F-actin purified from rabbit skeletal muscle undergoes reversible dissociation when subjected to hydrostatic pressures up to 240 MPa. Dissociation and reversibility were detected by the following procedures: fluorescence spectral changes observed under pressure, when either intrinsic tryptophan or pyrenyl emission of N-(1-pyrenyl)iodoacetamide-labeled actin were monitored; electron microscopy of samples fixed under pressure; size-exclusion HPLC of pressurized actin. The effect of pressure upon F-actin that had been polymerized in the presence of either Mg2+, Ca2+ or K+ was studied. The standard volume changes for the association of actin subunits, calculated from pressure/dissociation curves were 74 +/- 14 ml/mol for Mg-F-actin, 79 +/- 12 ml/mol for Ca-F-actin and 328 +/- 63 ml/mol for K-F-actin, indicating that actin subunits are packed differently in the polymer depending on which cation is present. All pressure/dissociation data could be fitted by a model for dissociation of a dimer, which suggests that in the F-actin filament there is a predominant intersubunit interaction interface, most likely the head-to-tail intrastrand interaction between two subunits which repeats itself along the polymer. A tenfold change in total protein concentration from 20 micrograms to 200 micrograms/ml Mg-F-actin did not cause a change in the pressure required for half-maximal dissociation. This indicates a heterogeneity of free energy of association among actin monomers in the Mg-F-actin polymer, suggesting that, in addition to the predominant intersubunit interaction, the disordered interactions in the filament significantly contribute to the heterogeneity of microenvironments in the interface between the subunits. PMID- 1425684 TI - Kinetic characterization of the perturbation by dodecylmaltoside of sarcoplasmic reticulum Ca(2+)-ATPase. AB - We investigated the functional aspects of the interaction between the sarcoplasmic reticulum (SR) membranous Ca(2+)-ATPase and the non-ionic detergent dodecylmaltoside, using detergent concentrations allowing perturbation of the membrane but not its solubilization. At pH 7.5, the effects of dodecylmaltoside on ATPase activity and delipidation had previously been shown to resemble, in some respects, those of octa(ethylene glycol) monododecylether (C12E8), an appropriate detergent for ATPase studies. Our aim here was to explore the specific effects of dodecylmaltoside on the different steps in the ATPase catalytic cycle, which may owe their specificity to the difference between the polar head groups of dodecylmaltoside and C12E8. This was done at 20 degrees C, both at pH 6 in the absence of KCl and at pH 7.5 in the presence of 100 mM KCl, two conditions under which the characteristics of unperturbed ATPase have already been well defined. Preliminary estimation of dodecylmaltoside partition between water and SR membranes at pH 6 yielded a partition coefficient K close to 4 x 10(5) (ratio of the molar fraction of dodecylmaltoside in the lipid to that in the aqueous phase at a low detergent concentration, assuming that most of this detergent was present in the lipid phase). At near saturation of SR membranes, bound dodecylmaltoside was roughly equimolar with the constituent phospholipids. Non-solubilizing concentrations of dodecylmaltoside inhibited SR ATPase activity by up to 65-70% at pH 7.5, but not at pH 6, unlike the results of similar experiments with C12E8. The rates of the four main steps in the ATPase catalytic cycle were measured by fast kinetic techniques; they were similarly modified at both pH. Dodecylmaltoside slowed down both the rate of calcium-saturated ATPase phosphorylation and the rate of ATPase isomerization after phosphorylation, two steps which were not targets of perturbation by C12E8. The slowing down of the isomerization step by dodecylmaltoside might well explain why it inhibited overall ATPase activity at pH 7.5. In contrast to C12E8, dodecylmaltoside did not affect the dephosphorylation step, which was the main target of inhibition by C12E8 and the main rate-limiting step at pH 6. However, like C12E8, dodecylmaltoside accelerated the calcium binding-induced transition of nonphosphorylated ATPase. Another striking feature of the perturbation induced by dodecylmaltoside was that it significantly altered the binding of 45Ca2+ to the ATPase and the corresponding conformational changes. At pCa 5-5.5, it almost halved calcium binding to the ATPase but ATPase phosphorylation was unimpaired.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1425685 TI - Characterization of fly rhodopsin kinase. AB - Rhodopsin kinase activity of Musca domestica was characterized in a reconstitution assay, using urea-treated eye membranes as substrate and a purified fraction of eye cytosol as the enzyme. Analysis of kinase activity in fly eye, brain and abdomen extracts by reconstitution assays revealed that fly rhodopsin kinase is an eye-specific enzyme. It preferentially phosphorylates the light-activated form of rhodopsin (metarhodopsin) and has little activity with other protein substrates. Rhodopsin kinase binds to metarhodopsin and is released from rhodopsin-containing membranes. Metarhodopsin is a poor substrate for kinases from tissues other than the eye, making it a unique substrate for rhodopsin kinase. Rhodopsin kinase is inhibited by heparin, but not by the protein inhibitor of cAMP-dependent protein kinase. Its Km for ATP is 9 microM. Since fly rhodopsin is coupled to phospholipase C, studies of the interaction of rhodopsin with rhodopsin kinase can be useful in analysis of the reactions that lead to termination of the inositol-phospholipid-signaling pathway. PMID- 1425686 TI - Regulation of two rat serine-protease inhibitor gene promoters by somatotropin and glucocorticoids. Study with intact hepatocytes and cell-free systems. AB - Only two out of the three serine-protease inhibitor genes (SPI 2.1, 2.2 and 2.3) expressed in rat liver are tightly controlled by somatotropin acting mainly at the transcriptional level, thus making this gene system particularly suitable to study its molecular mechanism of action. In these studies, we analyzed SPI promoter activities in cultured hepatocytes transfected by electroporation or in cell-free extracts. The proximal SPI 2.1 promoter region contains two somatotropin-responsive sites which are functional in intact cells. The more distal element that maps at positions -175 to -114, and is analogous to the one originally described by Yoon et al. (1990) [Yoon, J. B., Berry, S. A., Seelig, S. & Towle, H. C. (1990) J. Biol. Chem. 265, 19947-19954], behaves as a weak enhancer whose activity is strongly potentiated by proximal 5' downstream sequences that contains potential CCAAT-enhancer binding protein (C/EBP) sites. An additional proximal hormone-sensitive site is located in the close vicinity of the transcription-start site between positions -41 and +8, and also requires the first C/EBP-binding element to be active. The distal element appears to contribute more importantly (60%) than the proximal one (40%) to the overall somatotropin stimulation of chimeric gene expression. Nonetheless, both displayed similar dose-dependence, with half-maximal and maximal effects occurring at 0.5-1 nM and 5-10 nM, respectively. The somatotropin refractoriness of the SPI 2.3 gene appears to be due to the presence of distal (-2300 to -200) inhibitory element(s) in the promoter. Glucocorticoids exert both positive and negative effects on SPI promoter activity. Their stimulatory action appears to involve sequences located between positions -114 and -82, together with a more distal half glucocorticoid responsive element, whereas their inhibitory effect is more likely mediated by sequences located between positions -41 and +8. In vitro transcription assays, performed with promoter-deletion mutants and competitor oligonucleotides, revealed the presence of a major functional C/EBP site located immediately upstream from the transcription-start point. Unfortunately, the regulatory features of SPI gene expression observed in intact cells were completely obliterated by breaking down the cell structure, and could not therefore be studied using cell-free systems. PMID- 1425687 TI - Bacterial nitrite-reducing enzymes. AB - The enzymic reduction of nitrite takes place in a wide range of bacteria and is found to occur in denitrifying, assimilatory and dissimilatory pathways. In this review we describe the major molecular characteristics of the various enzymes employed in each of these processes. PMID- 1425688 TI - Alteration of translation and stability of mRNA for the poly(A)-binding protein during myogenesis. AB - The regulation of synthesis of various factors involved in mRNA translation during differentiation of muscle cells was examined. The steady-state levels of mRNAs coding for eukaryotic initiation factor (eIF) 2 alpha, 2 beta and elongation factor (eEF)-1 alpha were measured in both proliferating rat L6 myoblast and differentiated myotubes. The steady-state levels of these mRNAs were not altered during myogenesis. Furthermore, the distribution of these mRNAs between repressed and translated populations remained unchanged. Recent studies suggest a role for poly(A)-binding protein (PABP) in translation initiation. Therefore, we also examined the expression of PABP mRNA during myogenesis. The PABP mRNA was less abundant in myotubes compared to myoblasts. However, the synthesis of PABP remained unchanged. In myoblasts, approximately 50-60% of the total mRNA was associated with polyribosomes, whereas in myotubes more than 80% of the mRNA was associated with polyribosomes. These results, therefore, suggest that the PABP mRNA was more efficiently translated in differentiated myotubes than in the proliferating myoblasts. Measurement of the stability and transcription of PABP mRNA showed that, while transcription was not affected during myogenesis, the stability of the mRNA was reduced in differentiated cells. The t1/2 of PABP mRNA in myoblasts was 13 h compared to 7.5 h in myotubes. This observation suggests that the reduced steady-state level of PABP mRNA in myotube were largely due to the change in stability of this mRNA during myogenesis. PMID- 1425689 TI - Role of protein kinase C in induction of gene expression and inhibition of cell proliferation by interferon alpha. AB - Recent studies have suggested that protein kinase C (PKC) may be involved in the mechanism of signal transduction by which members of the interferon (IFN) family regulate gene expression and cell phenotype. We have investigated the role of PKC in the control of cell growth and gene expression by IFN alpha in Daudi cells. Treatment of these cells with two analogues of staurosporine, which are potent inhibitors of PKC, completely blocked the induction by IFN alpha of the mRNA for 2',5'-oligoadenylate synthetase and the 6-16 gene. These compounds also inhibited cell proliferation and thymidine incorporation in this system. In contrast, the protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7) did not significantly inhibit the induction of these genes by IFN alpha and had no effect on Daudi cell growth or thymidine incorporation in the presence or absence of IFN alpha. No effect of IFN alpha on total PKC activity could be observed, and there were no significant changes in the overall levels of individual PKC isoforms or their mRNA following IFN alpha treatment. In contrast, treatment of Daudi cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, which also inhibits cell proliferation, strongly down-regulated PKC. These data suggest that the activity of a PKC species, or a closely related enzyme, may be required both for continued cell proliferation and the response to IFN alpha in Daudi cells, but that IFN-induced growth inhibition does not involve overall down regulation or change in activity of PKC. PMID- 1425690 TI - Identification of functionally active fragments of staphylococcal enterotoxin B. AB - It has been found that staphylococcal enterotoxin B contains a proteolysis sensitive sequence in the cysteine loop formed by two half-cystines located in the middle of the toxin polypeptide chain. Fragments of the enterotoxin formed as a result of its digestion in this region have been isolated, their N-terminal sequences have been determined and sites of proteolysis have been identified. It has been demonstrated that the N-terminal fragment of staphylococcal enterotoxin B is capable of activating T cell proliferation in the culture of human mononuclear cells practically to the same degree as the intact enterotoxin. The toxin's C-terminal fragment possesses an ability to activate calmodulin-dependent enzymes and is probably the toxicogenic part of the enterotoxin. PMID- 1425691 TI - Effects of nucleotide binding on thermal transitions and domain structure of myosin subfragment 1. AB - The thermal unfolding and domain structure of myosin subfragment 1 (S1) from rabbit skeletal muscles and their changes induced by nucleotide binding were studied by differential scanning calorimetry. The binding of ADP to S1 practically does not influence the position of the thermal transition (maximum at 47.2 degrees C), while the binding of the non-hydrolysable analogue of ATP, adenosine 5'-[beta, gamma-imido]triphosphate (AdoPP[NH]P) to S1, or trapping of ADP in S1 by orthovanadate (Vi), shift the maximum of the heat adsorption curve for S1 up to 53.2 and 56.1 degrees C, respectively. Such an increase of S1 thermostability in the complexes S1-AdoPP[NH]P and S1-ADP-Vi is confirmed by results of turbidity and tryptophan fluorescence measurements. The total heat adsorption curves for S1 and its complexes with nucleotides were decomposed into elementary peaks corresponding to the melting of structural domains in the S1 molecule. Quantitative analysis of the data shows that the domain structure of S1 in the complexes S1-AdoPP[NH]P and S1-ADP-Vi is similar and differs radically from that of nucleotide-free S1 and S1 in the S1-ADP complex. These data are the first direct evidence that the S1 molecule can be in two main conformations which may correspond to different states during the ATP hydrolysis: one of them corresponds to nucleotide-free S1 and to the complex S1-ADP, and the other corresponds to the intermediate complexes S1-ATP and S1-ADP-Pi. Surprisingly it turned out that the domain structure of S1 with ADP trapped by p-phenylene-N, N' dimaleimide (pPDM) thiol cross-linking almost does not differ from that of the nucleotide-free S1. This means that pPDM-cross-linked S1 in contrast to S1 AdoPP[NH]P and S1-ADP-Vi can not be considered a structural analogue of the intermediate complexes S1-ATP and S1-ADP-Pi. PMID- 1425692 TI - Recombinant chicken egg white cystatin variants of the QLVSG region. AB - Using recombinant DNA methods, seven cystatin variants were produced by cassette mutagenesis of a chicken egg white cystatin variant which already contains the mutations Ala3, Glu2, Phe1, Ser1-->Met, Met29-->and Met 89-->Leu. When characterized by structural and functional studies, they were all found to harbour mutations in the first hairpin loop, the so-called 'QXVXG' region, which is highly conserved within the cystatin superfamily and thought to be important for its inhibitory activity towards cysteine proteinases. They were purified to more than 90% homogeneity and analysed by SDS/PAGE, HPLC, tryptic peptide mapping, N-terminal amino acid sequencing and ELISA. Structural model building of the variants and their complexes with papain was performed using computer graphics based on the crystallographic coordinates of chicken egg white cystatin and the papain-stefin complex. Only minor conformational changes were required for modelling the mutants or complexes. Equilibrium dissociation constants and rate constants of complex formation of the variants with papain, actinidin as well as cathepsin B and L were determined by kinetic measurements using fluorogenic substrates. The single exchanges Gln53-->Glu, Gln53-->Asn, Val44- >Asp, Gly57-->Ala and the double exchanges Arg52-->Leu, Gln53-->Glu, Gln53-->Asn, Ser56-->Ala, Leu54-->Met, Gly57-->Ala reduced the inhibition of papain, actinidin and cathespin B significantly by 10-1000-fold. With the exception of the Val55- >Asp variant, the differences in the Ki values are mainly due to larger k off values, whereas the kon values seem to be more or less unaffected by the selected mutations. The effect on the inhibition of papain is generally smaller than the effects on actinidin and cathepsin B inhibition. Cathepsin L inhibition is strikingly insensitive to all mutations. These distinct effects of the inhibitor variants indicate differences in proteinase-inhibitor-protein interactions between closely related cysteine proteinases. In addition, the results verify the prediction, made earlier from sequence alignment studies and from a docking model of the chicken cystatin-papain complex, that the first hairpin loop of cystatins is essential for effective inhibition. PMID- 1425693 TI - Chemical and structural characterisation of iron cores of haemosiderins isolated from different sources. AB - The elemental content of the iron cores of haemosiderins isolated from animal and human tissues has been determined to ascertain whether changes in composition are correlated with structural differences previously identified in these mineralisation products. Significant differences were observed in the elemental composition of haemosiderins isolated from patients subjected to desferrioxamine chelation therapy compared to patients who had been venesected. The P/Fe molar ratio was considerably higher in haemosiderin isolated from treated primary haemochromatosis (0.83), compared to untreated primary haemochromatosis (0.10) and treated secondary haemochromatosis (0.25), and this could account for the amorphous nature of these iron cores. The levels of M/Fe (M = Ca, Cu, Zn) were reduced in the haemosiderins derived from treated secondary haemochromatosis patients, possibly due to the chelation of these ions by desferrioxamine therapy. In an experimentally iron-loaded rat, receiving either desferrioxamine or 1,2 diethyl-3-hydroxypyrid-4-one, selective decreases in these three elements were also observed after two weeks of desferrioxamine therapy. Such changes may be important determinants in the modification of biomineralisation of the iron cores. PMID- 1425694 TI - Characterization of [3H]acifluorfen binding to purified pea etioplasts, and evidence that protoporphyrinogen oxidase specifically binds acifluorfen. AB - It is now generally accepted that protoporphyrinogen oxidase is the target-enzyme for diphenyl-ether-type herbicides. Recent studies [Camadro, J-M., Matringe M., Scalla, R. & Labbe, P. (1991) Biochem. J. 277, 17-21] have revealed that in maize, diphenyl ethers competitively inhibit protoporphyrinogen oxidase with respect to its substrate, protoporphyrinogen IX. In this study, we show that, in purified pea etioplast, [3H]acifluorfen specifically binds to a single class of high-affinity binding sites with an apparent dissociation constant of 6.2 +/- 1.3 nM and a maximum density of 29 +/- 5 nmol/g protein. [3H]Acifluorfen binding reaches equilibrium in about 1 min at 30 degrees C. Half dissociation occurs in less than 30 s, indicating that the binding is fully reversible. The specificity of [3H]acifluorfen binding to protoporphyrinogen oxidase is examined. [3H]Acifluorfen binding is inhibited by all the peroxidizing molecules tested. The phthalimide derivative, N-(4-chloro-2-fluoro-5-isopropoxy)phenyl-3,4,5,6 tetra hydrophthalimide, exerts a mixed-competitive inhibition on this binding. The effects of all these molecules on the binding of [3H]acifluorfen are tightly linked to their capacity to inhibit pea etioplast protoporphyrinogen oxidase activity. Furthermore, protoporphyrinogen IX, the substrate of the reaction catalyzed by protoporphyrinogen oxidase, was able to competitively inhibit the binding of [3H]acifluorfen. In contrast, protoporphyrin IX, the product of the reaction, did not inhibit this binding. All these results provide clear evidence that in pea etioplasts, [3H]acifluorfen exclusively binds to protoporphyrinogen oxidase, that the protoporphyrinogen oxidase inhibitors tested so far bind to the same region of the enzyme and that this region overlaps the catalytic site of the enzyme. PMID- 1425695 TI - Mutational replacements in subtilisin 309. Val104 has a modulating effect on the P4 substrate preference. AB - The previous notion that the amino acid side chain at position 104 of subtilisins is involved in the binding of the side chain at position P4 of the substrate has been investigated. The amino acid residue Val104 in subtilisin 309 has been replaced by Ala, Arg, Asp, Phe, Ser, Trp and Tyr by site-directed mutagenesis. It is shown that the P4 specificity of this enzyme is not determined solely by the amino acid residue occupying position 104, as the enzyme exhibits a marked preference for aromatic groups in P4, regardless of the nature of the position 104 residue. With hydrophilic amino acid residues at this position, no involvement is seen in binding of either hydrophobic or hydrophilic amino acid residues at position P4 of the substrates. The substrate with Asp in P4 is an exception, as the preference for this substrate is increased dramatically by introduction of an arginine residue at position 104 in the enzyme, presumably due to a substrate-induced conformational change. However, when position 104 is occupied by hydrophobic residues, it is highly involved in binding of hydrophobic amino acid residues, either by increasing the hydrophobicity of S4 or by determining the size of the pocket. The results suggest that the amino acid residue at position 104 is mobile such that it is positioned in the S4 binding site only when it can interact favourably with the substrate's side chain at position P4. PMID- 1425696 TI - Structure of the acidic N-linked carbohydrate chains of the 55-kDa glycoprotein family (PZP3) from porcine zona pellucida. AB - N-linked carbohydrate chains of the major 55-kDa family, PZP3, of porcine zona pellucida glycoproteins are composed of neutral (28%) and acidic (72%) complex type chains. The structures of the main components of the neutral chain have been established [Noguchi, S., Hatanaka, Y., Tobita, T. & Nakano, M. (1992) Eur. J. Biochem. 204, 1089-1100]. Here we report the structures of the acidic chains. Only two kinds of acidic fragments were released from PZP3 by endo-beta galactosidase digestion following beta-elimination of O-linked chains. 500-MHz one-dimensional and two-dimensional 1H-NMR spectroscopy revealed their structures to be Sia alpha(2-3)Gal beta(1-4) [HSO3-6]GlcNAc beta(1-3)Gal and HSO3-6GlcNAc beta(1-3)Gal, showing that the sulfate-containing acidic chains are constructed with non-branched N-acetyllactosamine repeats which have sialic acid(s) at the non-reducing end(s) and sulfate at the C-6 position of GlcNAc residues. The acidic N-linked chains obtained from PZP3 by hydrazinolysis were separated into diantennary chains (34%) and tri- and tetra-antennary chains (66%) by concanavalin-A--agarose gel chromatography. The diantennary chains and their sialidase digests were fractionated by DEAE-HPLC. From the analyses of the endo beta-galactosidase digests of each fraction, structures of the diantennary acidic chains were determined. They are classified into four groups. The first group is the sialylated chains without the sulfated N-acetyllactosamine repeating unit. The other three groups have the chains of various lengths differing in the number of monosulfated N-acetyllactosamine unit. These chains are extended from the Man alpha(1-3) branch of the trimannosyl core in the second group, from the Man alpha(1-6) branch in the third group, and from both branches in the fourth group. The structural features of the tri- and tetra-antennary acidic chains are also presented. PMID- 1425697 TI - The Asn-linked carbohydrate chains of human Tamm-Horsfall glycoprotein of one male. Novel sulfated and novel N-acetylgalactosamine-containing N-linked carbohydrate chains. AB - Human Tamm-Horsfall glycoprotein has been purified from the urine of one male. The Asn-linked carbohydrate chains were enzymically released by peptide-N4-(N acetyl-beta-glucosaminyl)asparagine amidase F, and separated from the remaining protein by gel-permeation chromatography on Bio-Gel P-100. Fractionation of the intact (sulfated) sialylated carbohydrate chains was achieved by a combination of three liquid-chromatographic techniques, namely, anion-exchange FPLC on Q Sepharose, amine-adsorption HPLC on Lichrospher-NH2, and high-pH anion-exchange chromatography on CarboPac PA1. In total, more than 150 carbohydrate-containing fractions were obtained, some of which still contained mixtures of oligosaccharides. The primary structure of 30 N-glycans, including 10 novel oligosaccharides, were determined by one- and two-dimensional 1H-NMR spectroscopy at 500 MHz or 600 MHz. The types of compounds identified range from non fucosylated, monosialylated, diantennary to fucosylated, tetrasialylated, tetraantennary carbohydrate chains, possessing the following terminal structural elements: [formula: see text] PMID- 1425698 TI - Thioredoxin regenerates proteins inactivated by oxidative stress in endothelial cells. AB - The thioredoxin/thioredoxin reductase system has been studied as regenerative machinery for proteins inactivated by oxidative stress in vitro and in cultured endothelial cells. Mammalian glyceraldehyde-3-phosphate dehydrogenase was used as the main model enzyme for monitoring the oxidative damage and the regeneration. Thioredoxin and its reductase purified from bovine liver were used as the regenerating system. The physiological concentrations (2-14 microM) of reduced thioredoxin, with 0.125 microM thioredoxin reductase and 0.25 mM NADPH, regenerated H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase and other mammalian enzymes almost completely within 20 min at 37 degrees C. Although the treatment of endothelial cells with 0.2-12 mM H2O2 for 5 min resulted in a marked decrease in the activity of glyceraldehyde-3-phosphate dehydrogenase, it had no effect on the activities of thioredoxin and thioredoxin reductase. Essentially all of the thioredoxin in endothelial cells at control state was in the reduced form and 70-85% remained in the reduced form even after the H2O2 treatment. The inactivated glyceraldehyde-3-phosphate dehydrogenase in a cell lysate prepared from the H2O2-treated endothelial cells was regenerated by incubating the lysate with 3 mM NADPH at 37 degrees C and the antiserum raised against bovine liver thioredoxin inhibited the regeneration. The inhibition of thioredoxin reductase activity by 13-cis-retinoic acid resulted in a decrease in the regeneration of glyceraldehyde-3-phosphate dehydrogenase in the H2O2-treated endothelial cells. The present findings provide evidence that thioredoxin is involved in the regeneration of proteins inactivated by oxidative stress in endothelial cells. PMID- 1425699 TI - Corn kernel cysteine proteinase inhibitor as a novel cystatin superfamily member of plant origin. Molecular cloning and expression studies. AB - A full-length cDNA clone for a cysteine proteinase inhibitor (cystatin) was isolated from a lambda gt10 cDNA library of immature corn kernels by screening with a mixture of cDNA inserts for oryzacystatins I and II. The cDNA clone spans 960 base pairs, encoding a 135-amino-acid protein containing a signal peptide fragment. The protein, named corn cystatin I, is considered to be a member of the cystatin superfamily, since it contains the commonly conserved Gln-Val-Val-Ala Gly region that exists in most known cystatins as a probable binding site and is significantly similar to other cystatins in its overall amino acid sequence. Corn cystatin I expressed in Escherichia coli showed a strong papain-inhibitory activity. Northern blot analysis showed that the amount of mRNA for corn cystatin I reaches a maximum 2 weeks after flowering and then decreases gradually. PMID- 1425700 TI - Purification and characterization of a hemocyte proteinase of Sarcophaga, possibly participating in elimination of foreign substances. AB - We have reported that foreign protein injected into the abdominal cavity of Sarcophaga peregrina (flesh fly) larvae is degraded in the hemolymph by a proteinase secreted by hemocytes [Suzuki, T. and Natori, S. (1985) Comp. Biochem. Physiol. 81A, 191-193]. Here we report the purification and characterization of a proteinase from larval hemocytes. This enzyme is a cysteine proteinase consisting of 26-kDa and 29-kDa subunits with similar substrate specificity to mammalian cathepsin B. This enzyme was shown to be released from hemocytes into the hemolymph of larvae following injection of sheep red blood cells into the larvae, suggesting that it participates, at least in part, in elimination of foreign substances introduced into the body cavity. PMID- 1425701 TI - Specific phosphorylation of the acidic central region of the N-myc protein by casein kinase II. AB - The central region of the N-myc protein has a characteristic amino acid sequence EDTLSDSDDEDD, which is very similar to those of particular domains of adenovirus E1A, human papilloma virus E7, Simian virus 40 large T, c-myc and L-myc proteins. Domains of these three viral oncoproteins have recently been shown to be specific binding sites for the tumor-suppressor gene retinoblastoma protein. We have noted that the sequence of serine followed by a cluster of acidic amino acids is exactly the same as that of a typical substrate of casein kinase II (CKII). Therefore, we investigated whether these nuclear oncoproteins are phosphorylated by CKII. For this purpose, we fused the beta-galactosidase and N-myc genes including this domain and expressed it in Escherichia coli cells. Several mutant N-myc genes, containing single amino acid substitutions in this domain, were also used to produce fused proteins. Strong phosphorylation by CKII was detected with the fused protein of wild-type N-myc. However, no phosphorylation of beta galactosidase itself was observed and the phosphorylations of fused mutant proteins were low. Another fused N-myc protein containing most of the C-terminal region downstream of this acidic region was not phosphorylated by CKII. Analysis of phosphorylation sites in synthetic peptides of this acidic region identified the major sites phosphorylated by CKII as Ser261 and Ser263. On two-dimensional tryptic mapping of phosphorylated N-myc proteins, major spots of in vitro-labeled and in-vivo-labeled N-myc proteins were detected in the same positions. These results suggest that two serine residues of the acidic central region of the N myc protein are phosphorylated by CKII in vivo as well as in vitro. The functional significance of this acidic domain is discussed. PMID- 1425702 TI - Characterization of the 56-kDa subunit of yeast trehalose-6-phosphate synthase and cloning of its gene reveal its identity with the product of CIF1, a regulator of carbon catabolite inactivation. AB - Trehalose-6-phosphate synthase is the key enzyme for biosynthesis of trehalose, the major soluble carbohydrate in resting cells of yeast. This enzyme was purified from a strain of Saccharomyces cerevisiae lacking vacuolar proteases. It was found to be a multimeric protein of 630 kDa. Monoclonal antibodies were raised against its smallest subunit (56 kDa) and used for screening a yeast cDNA library. This yielded an immunopositive cDNA clone of 1.7 kb, containing an open reading frame of 1485 base pairs. Its sequence, called TPS1 (for trehalose-6 phosphate synthase), was represented by a single gene in the yeast genome and was found to be almost identical with the recently sequenced CIF1, a gene important for carbon catabolite inactivation, believed to be allelic with FDP1. A mutant obtained by disruption of TPS1 had a very low activity of trehalose-6-phosphate synthase, indicating that TPS1 is an important component of the enzyme. The mutant also showed a growth defect when transferred from glycerol to glucose, a phenotype similar to that of the cif1 and fdp1 mutants deficient in carbon catabolite inactivation. Thus, the smallest subunit of the biosynthetic enzyme trehalose-6-phosphate synthase appears to have, in addition, a central regulatory role in the carbohydrate metabolism of yeast. PMID- 1425703 TI - Germin isoforms are discrete temporal markers of wheat development. Pseudogermin is a uniquely thermostable water-soluble oligomeric protein in ungerminated embryos and like germin in germinated embryos, it is incorporated into cell walls. AB - Nascent synthesis and accumulation of germin and its mRNA mark the onset of renewed growth when wheat embryos are germinated in water. Germin is a water soluble, pepsin-resistant protein that is not found in immature embryos, or in mature embryos before their germination. An antiserum was raised by injecting rabbits with germin that was freed of other proteins by pepsinization and gel filtration. The antiserum has been used to detect, in extracts of mature embryos from dry, ungerminated wheat grains, a protein that is antigenically related to germin. The antigenically related protein has been named pseudogermin. Pseudogermin accumulates, maximally, between 20-25-days postanthesis, then declines appreciably in amount by 30-days postanthesis, in soluble extracts of immature embryos from several wheat varieties. The antiserum was also used to identify germin and pseudogermin among the proteins extracted from cell walls and to bind immunogold to cell walls preparatory to visualizing freeze-cleaved embryos by scanning electron microscopy. Wall-associated germin accounts for about 40% of the total germin in germinating wheat embryos. Appearance of germin in the apoplast is the most conspicuous germination-related change in the distribution of cell-wall proteins. It seems that germin may act at the level of the apoplast and that pseudogermin may subsume the role of germin at low water potentials during embryogenesis. The N-terminal eicosapeptide sequences in germin and pseudogermin are very similar but SDS/PAGE analysis detects discrete differences between the mobilities of their constituent monomers as well as gross differences between the stabilities of the parent oligomers. Like germin, pseudogermin is a water-soluble, pepsin-resistant protein, but pseudogermin has unprecedented disulphide-independent thermostability properties that have never been previously reported for a water-soluble oligomeric protein. Polysaccharides that co-purify with otherwise pure specimens of germin (and pseudogermin) have been isolated for analysis and shown to be highly substituted glucuronogalactoarabinoxylans. The possible biological significance of selective and tenacious association between germin and glucuronogalactoarabinoxylans is discussed in relation to cell expansion during embryogenic and germinative development of wheat, as are some peculiarities of amino-acid sequence that suggest a possible relation between germin and a proton-specific ion pump: gastric ATPase. PMID- 1425704 TI - Wheat Ec metallothionein genes. Like mammalian Zn2+ metallothionein genes, wheat Zn2+ metallothionein genes are conspicuously expressed during embryogenesis. AB - A cDNA library was prepared from the bulk mRNA of mature wheat embryos and screened with mixed 32P-labeled oligonucleotide probes that encoded parts of the partial amino-acid sequence for the Zn-containing Ec protein. Each DNA insert in 11 positives from a screen of 10(5) plaques encoded a 5' untranslated and a 3' untranslated region, in addition to an open reading frame (of 81 amino acids) which, in every case, corresponded to at least 56 of the 59 amino acids in the partial polypeptide sequence previously determined for the Ec protein. The three different mRNA sequences encoded in the cDNA probably correspond to single-copy genes in the A, B and D genomes of hexaploid wheat. A wheat genomic library was screened with 32P-labeled cDNA and gave a single positive in a screen of 5 x 10(5) plaques. A 3.1-kb genomic fragment (gf-3.1) was sequenced and a cap site for the encoded mRNA was determined by primer extension. The gf-3.1 sequence encodes an intronless mRNA for the Ec protein and contains appreciable amounts of 5' and 3' flanking sequences. In addition to a putative TATA box, two inverted repeat sequences and one direct-repeat sequence, the 5' flank in gf-3.1 contains a sequence similar to the abscisic-acid-responsive element in other higher-plant genes but does not contain sequences similar to the metal-responsive elements in animal metallothionein genes. Consistent with these findings, RNA blotting shows that accumulation of Ec mRNA is abundant in immature embryos, undetectable in germinated embryos and can be induced by adding abscisic acid, but not by adding Zn2+ to the medium in which mature wheat embryos are germinated. The findings suggest that the wheat Ec metallothionein genes, like mammalian liver metallothionein genes, are conspicuously expressed during embryogenesis. PMID- 1425705 TI - A novel insect defensin mediates the inducible antibacterial activity in larvae of the dragonfly Aeschna cyanea (Paleoptera, Odonata). AB - The injection of low doses of bacteria into the aquatic larvae of dragonflies (Aeschna cyanea, Odonata, Paleoptera) induces the appearance in their hemolymph of a potent antibacterial activity. We have isolated a 38-residue peptide from this hemolymph which is strongly active against Gram-positive bacteria and also shows activity against one of the Gram-negative bacteria which was tested. The peptide is a novel member of the insect defensin family of inducible antibacterial peptides, which had so far only been reported from the higher insect orders believed to have evolved 100 million years after the Paleoptera. Aeschna defensin is more potent than defensin from the dipteran Phormia, from which its structure differs in several interesting aspects, which are discussed in the paper. PMID- 1425706 TI - A substrate-like form of plasminogen-activator-inhibitor type 1. Conversions between different forms by sodium dodecyl sulphate. AB - Recombinant plasminogen-activator-inhibitor type 1 (PAI-1) purified in an active form from Escherichia coli and eucaryotic cells was found to contain a mixture of three functionally distinct forms: an active form that forms complexes with plasminogen activators (PAs), an inactive (latent) form that remains intact after incubation with PAs, and a substrate-like form which is easily cleaved by PAs. Since active PAI-1 purified from bacteria (rpPAI-1) contains only trace amounts of the inactive latent and the substrate-like forms, this material was used to study the effect of sodium dodecyl sulphate (SDS) on the structure and function of active PAI-1. After treatment with 0.01% SDS, active rpPAI-1 was converted to an inactive form that did not form complexes with PAs, but exhibited characteristics similar to those of latent PAI-1. After treatment with 0.1% SDS, PAI-1 lost its inhibitory activity and was cleaved as a substrate in the reactive center. Circular dichroism spectral analysis reveals that SDS changed the conformation of PAI-1 dramatically, mainly by increasing its alpha-helical content. PMID- 1425707 TI - Unusual amino acid substitution in the anion-binding site of Lactobacillus plantarum non-allosteric L-lactate dehydrogenase. AB - In Lactobacillus plantarum non-allosteric L-lactate dehydrogenase (L-LDH), the highly conserved His188 residue, which is involved in the binding of an allosteric effector, fructose 1,6-bisphosphate [Fru(1,6)P2], in allosteric L-LDH is uniquely substituted by an Asp. The mutant L. plantarum L-LDH, in which Asp188 is replaced by a His, showed essentially the same Fru(1,6)P2-independent catalytic activity as the wild-type enzyme, except that the Km and Vmax values were slightly decreased. However, the addition of Fru(1,6)P2 induced significant thermostabilization of the mutant enzyme, as in the case of many allosteric L LDHs, while Fru(1,6)P2 showed no significant effect on the stability of the wild type enzyme, indicating that only the single-point mutation, G-->C, sufficiently induces the Fru(1,6)P2-binding ability of L. plantarum L-LDH. The mutant enzyme showed higher thermostability than the wild-type enzyme in the presence of Fru(1,6)P2. In the absence of Fru(1,6)P2, on the other hand, the mutant enzyme was more labile below 65 degrees C but more stable above 70 degrees C. PMID- 1425708 TI - Cloning and specific polymerised-chain-reaction amplification of a third charge separable human metallothionein isoform. AB - Metallothionein (MT) fractions isolated from human adult liver tissue are readily separated by anion-exchange chromatography in two isoforms, MT-1 and MT-2, which differ from each other in the nature of the amino acid residue at position 11. In fetal liver tissue, the presence of a third charge-separable MT isoform has been previously reported. We determined its partial amino acid sequence and the sequence of a cDNA clone encoding this MT form. This confirmed the existence of another human MT isoform, hereafter named MT-0, which is characterized by the presence of a negatively charged amino acid at position 8, and by a Glu23 to Lys substitution in a strictly conserved region of the protein. Taking into account these substitutions, we are able to classify human MT isoforms into three instead of two charge-separable groups, based on the nature of three amino acid residues. The unique presence of Glu8 in MT-0 enabled us to develop an MT-0-specific amplification by the polymerase chain reaction, which revealed the presence of MT 0 mRNA in adult liver RNA samples, in spite of the total absence of this isoform at the protein level. This suggests the involvement of post-transcriptional regulatory mechanisms in the expression of this fetal MT form. PMID- 1425709 TI - Efficacy of fluconazole in the treatment of systemic fungal infections. AB - The efficacy of fluconazole in the treatment of systemic fungal infections was evaluated in an open non-comparative trial. A total of 48 patients with proven or suspected fungal infections were enrolled in 40 of whom efficacy was evaluable. Candida albicans accounted for 90% of the infections. Candida parapsilosis, Candida glabrata, Histoplasma capsulatum and Aspergillus fumigatus caused the infection in one case each. Fluconazole was administered at a dosage of 200-400 mg daily for a mean duration of 15 days. Fluconazole treatment was successful in 53% of the patients. In patients with proven or probable Candida albicans infections a clinical and mycological response was achieved in 62% and 65%, respectively. In 11 patients elevation of liver enzymes was considered to be possibly related to fluconazole treatment; modification of treatment was not necessary in any case. Fluconazole was found to be a well tolerated and effective agent for the treatment of systemic Candida albicans infections. PMID- 1425710 TI - Value of differential quantitative blood cultures in the diagnosis of catheter related sepsis. AB - A prospective study was performed to assess the value of differential quantitative blood cultures in the diagnosis of catheter-related sepsis when this condition is suspected on clinical grounds and to establish a reliable discriminative value for application without removal of the inserted catheter. A total of 107 central venous catheters from 64 patients were used for the study. Blood was obtained simultaneously through the suspected infected device and from a peripheral venipuncture. The catheter was removed and its tip cultured semiquantitatively. Catheter-related sepsis occurred in 17 patients. Using as cut off value a colony count fourfold higher in blood drawn through the catheter than in simultaneously drawn peripheral blood, a sensitivity of 94%, specificity of 100% and positive predictive value of 100% were obtained. A single bacterial count greater than 100 cfu/ml in the quantitative culture of the catheter blood specimen in the presence of a positive qualitative peripheral blood culture of the same organism was also highly suggestive of catheter-related sepsis. Differential quantitative blood culture is a reliable method for the diagnosis of catheter-associated sepsis without catheter removal. PMID- 1425711 TI - In vitro and in vivo effect of antibiotics on catheters colonized by staphylococci. AB - An in vitro model was used to study whether and how catheter infections can be cured. Silastic catheters were "infected" with Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis KH11 and V2; these "infections" were then treated with 24, 48 and 96 h continuous infusions of various antimicrobial agents administered both as monotherapy and in combination. The Staphylococcus aureus strain was considerably more difficult to eliminate from catheters than were the Staphylococcus epidermidis strains. This experience gained in the laboratory was then applied in vivo to 16 episodes of catheter sepsis in seven children. Treatment for at least six days with imipenem/cilastatin combined with fosfomycin or an aminoglycoside successfully eliminated the pathogens isolated from 11 of the 16 episodes of infection. The broad-spectrum combination was chosen because it could not be assumed that individual pathogens would be sensitive to a single substance. Nine of the infected catheters could be retained in the patients. This experience suggests that it may be possible to successfully eliminate the colonization of central venous catheters by coagulase-negative staphylococci using the antimicrobial agents employed here. PMID- 1425712 TI - Spectrum of disease in bacteraemic patients during a Streptococcus pyogenes serotype M-1 epidemic in Norway in 1988. AB - All 87 known cases of bacteraemia due to Streptococcus pyogenes (beta-haemolytic group A streptococci) occurring during the peak of a nationwide outbreak in Norway (population 4.2 million) between January and June 1988 were reviewed. Clinical features varied widely and appeared largely to be dependent on the patients' age. The case fatality rate ranged from 11% in the age group under 30 years to 44% in patients over 60 years. Clinical complications such as shock, severe renal or respiratory failure or serious local infection occurred particularly in 30-to 59-year old individuals. Shock was manifest in 32% of the patients and carried a 68% case fatality rate. Chronic heart disease in the elderly and pneumonia seemed to be associated with a fatal outcome. In the 25 patients (29%) who died the disease showed a fulminant course, 80% dying within 48 hours after admission. However, 56% of the patients had experienced symptoms for more than two days before admission, suggesting that early diagnosis and treatment might possibly have prevented the development of a serious disease. This study revealed a wide spectrum of clinical manifestations in bacteraemia cases in a unique epidemiological situation caused largely by a single serotype of Streptococcus pyogenes; 89% of the 27 preserved bacteraemia strains carried the M-1 antigen. The observations call attention to the ability of these organisms to cause fulminant clinical illness, indicating a probable increase in both invasiveness and toxicity of group A streptococci responsible for the epidemic. PMID- 1425713 TI - Evaluation of ciprofloxacin and doxycycline in the treatment of Mediterranean spotted fever. AB - A comparison was made of the results obtained with ciprofloxacin (750 mg/12 h) and doxycycline (100 mg/12 h), both administered p.o. for one week, in 34 and 36 patients respectively with Mediterranean spotted fever. Apyrexia was achieved after 50.1 +/- 34.2 h (mean +/- SD) of antibiotic therapy in the group of patients treated with ciprofloxacin and in 55.2 +/- 23.3 h in the group treated with doxycycline (no significant statistical differences). Resolution of the remaining signs and symptoms of the disease was achieved faster with ciprofloxacin. Both therapeutic regimens were effective and safe. Although more expensive than doxycycline, ciprofloxacin is a bactericidal compound which is better tolerated and has a lower risk of toxicity and of development of resistance. It can be considered, together with doxycycline, as an antibiotic of first choice in the treatment of Mediterranean spotted fever. PMID- 1425714 TI - Evaluation of an enzyme immunoassay using neoglycolipids constructed from Candida albicans oligomannosides to define the specificity of anti-mannan antibodies. AB - In order to study the respective roles of oligomannoside sequences in the antigenicity of Candida albicans phosphopeptidomannan, a method was developed for constructing neoglycolipids from oligomannosides released by depolymerisation of this molecule. Oligomannosides released by acetolysis were converted to neoglycolipids by coupling them to 4-hexadecylaniline in an equimolar reaction checked by thin layer chromatography. When coated onto microEIA plates, the neoglycolipids exhibited strong reactions which were dose dependent and were saturable with concanavalin A. Reactivity of neoglycolipids with immunoglobulins were then tested with a panel of monoclonal and polyclonal antibodies reacting with epitopes present in the original phosphopeptidomannan. One of two IgM monoclonal antibodies and two of five monospecific rabbit polyclonal IgG reacted strongly with neoglycolipids therefore providing evidence of the presence of structures mimicking epitopes within the pool of neoglycolipids. When 38 sera from 18 hospital inpatients with various levels of antibodies to Candida albicans were tested, a correlation was observed between the EIA to detect neoglycolipids and the EIA to detect phosphopeptidomannan. Successive sera from all patients showing seroconversion in the immunofluorescence assay had increased EIA signals for neoglycolipids. PMID- 1425715 TI - Treatment of tularemia with ciprofloxacin. AB - A case of tularemia which occurred after close contact with a cat is presented. After unsuccessful amoxicillin treatment, a two-week course of doxycycline was given whereupon the patient responded well. However, the patient relapsed shortly after and was then given ciprofloxacin for two weeks. The patient then recovered completely. Clinical trials are needed in order to establish whether a quinolone could be the drug of choice for treatment of tularemia. PMID- 1425716 TI - Evaluation of a latex test for rapid detection of pneumococcal antigens in sputum. AB - A latex agglutination test (Directigen) for detection of pneumococcal capsular polysaccharide antigens in sputum was evaluated in comparison to culture and Gram stain using 121 sputum specimens. The sensitivity, specificity and rate of agreement of the latex test compared to culture were 90%, 79% and 81%, respectively. The results suggest that the latex test may be useful for detecting pneumococcal antigen in sputum. PMID- 1425717 TI - Evaluation of three rapid enzyme immunoassays and cell culture for detection of respiratory syncytial virus. AB - Three rapid enzyme immunoassay techniques for the detection of respiratory syncytial virus antigen (Becton Dickinson Directigen RSV, Abbott RSV Testpack and Abbott RSV EIA) and cell culture were evaluated in a total of 250 nasal washings. The sensitivity and specificity were 62% and 76% respectively for Directigen, 64% and 86% for RSV Testpack, and 76% and 81% for RSV EIA, taking cell culture as the reference method. Agreement between cell culture and EIA techniques was 79% (70 positive and 128 negative results). All three EIA techniques gave positive results in 69 samples (52 positive and 17 negative in the cell culture). In 121 samples all three EIA techniques gave negative results (103 negative and 18 positive in the cell culture). Using the cell culture technique 46 strains other than respiratory syncytial virus were isolated. PMID- 1425718 TI - Pharmacokinetics of roxithromycin and influence of H2-blockers and antacids on gastrointestinal absorption. AB - The pharmacokinetics of roxithromycin (300 mg orally) and the influence of the antacid aluminum magnesium hydroxide and the H2-blocker ranitidine on bioavailability of roxithromycin in ten healthy volunteers were studied. Pharmacokinetics after a single dose of roxithromycin were characterized by high peak serum levels (9.1 +/- 2.1 mg/l) and a long elimination half-life (7.2 +/- 2.5 h), resulting in a large area under the curve (116.9 +/- 32.7 mg h/l). High inter- and intraindividual variations were found for both the absorption time and the elimination half-life. The bioavailability of roxithromycin was not affected by coadministration with antacids or ranitidine. PMID- 1425719 TI - Congenital pneumonia and early neonatal septicemia due to Bacteroides fragilis. PMID- 1425720 TI - Corynebacterium jeikeium meningitis and transverse myelitis in a neutropenic patient. PMID- 1425721 TI - Changes in the sensitivity of urinary pathogens to quinolones between 1987 and 1990 in France. PMID- 1425722 TI - Determination of antibody titres for Borrelia burgdorferi in the serum of gipsies living in Attika, Greece. PMID- 1425723 TI - Seroprevalence of Chlamydia pneumoniae in the normal population. PMID- 1425724 TI - A French case of rabies in Europe. PMID- 1425725 TI - Serious complications of vascular catheter-related Staphylococcus aureus bacteremia in cancer patients. AB - Over the period 1986 to 1989, 53 cancer patients were identified with catheter related Staphylococcus aureus bacteremia at the University of Texas M.D. Anderson Cancer Center. Septic thrombosis was diagnosed in 12 (23%) patients and was suspected in another 3 (6%). Of the 12 patients, five developed deep-seated infections (septic emboli, endocarditis, meningitis, abscess), compared with 2 of the 38 other patients with no septic thrombosis (p < 0.01). Fever persisted for more than three days after antibiotic initiation in 52% of the patients with complications (septic thrombosis and/or deep-seated infections), compared with 19% of those without complications (p < 0.02). Of the three patients with complications who were treated for 14 days with intravenous antistaphylococcal antibiotics, two relapsed; in contrast, all of the nine patients with complications who were treated for more than 14 days (mean 4 weeks) were cured, and none relapsed (p < 0.05). Of the nine patients with complications who were treated with a long course of therapy, only one required surgery. The possibility of septic thrombosis and/or deep-seated infections should be considered in all cancer patients with catheter-related Staphylococcus aureus bacteremia, and if present, the condition should be treated with appropriate intravenous antibiotics for at least four weeks. PMID- 1425726 TI - Randomized multicenter clinical trial with imipenem/cilastatin versus cefotaxime/gentamicin in the treatment of patients with non-life-threatening infections. German and Austrian Imipenem/Cilastatin Study Group. AB - In an open, controlled, randomized study the safety and efficacy of imipenem/cilastatin was compared with that of the combination cefotaxime/gentamicin (plus metronidazole in patients with suspected anaerobe infection) in the treatment of 337 patients from 12 German and 5 Austrian centers who had non-life-threatening infections. The evaluation was done on an intention to-treat basis (i.e. all patients including protocol violators) and according to the protocol (144 patients in the imipenem/cilastatin group and 124 in the cefotaxime/gentamicin group). No significant differences were seen between the two treatment groups in terms of the clinical and bacteriological outcome. The frequency of infusion intolerance and thrombophlebitis was low in both groups (< 2%). The overall rate of adverse events was comparable in the two groups, nausea, vomiting and diarrhea being the most frequent events. Nephrotoxicity, indicated by an increase in serum creatinine, was significantly higher in the cefotaxime/gentamicin group. Imipenem/cilastatin was shown to be as effective as cefotaxime/gentamicin (metronidazole) and appears to be well tolerated. PMID- 1425727 TI - Characteristics of Pseudomonas aeruginosa strains causing septicemia in a Spanish hospital 1981-1990. AB - The epidemiological and biochemical characteristics of Pseudomonas aeruginosa strains causing septicemia in a Spanish hospital over a ten-year period (1981 1990) were analyzed. A total of 207 episodes, corresponding to 0.7 episodes per 1,000 inpatients and 3.2% of the total number of episodes of septicemia, were registered. Males were more often affected than females (rate 3.2:1). The respiratory (24.6%) and urinary (21.2%) tracts were the main portals of entry, while haematologic and solid tumours (15.4%) were the most frequent underlying diseases. More than 86% of the strains were susceptible to ceftazidime, mezlocillin, piperacillin and amikacin. Seventy strains were subjected to typing and analysis of virulence factors. Serotypes O:6, O:11 and O:2 could be considered endemic (each present in more than 11.4% of strains). Pyocin typing, antibiotyping and resistotyping were preferred as secondary typing methods to phage typing and plasmid profile analysis. The combination of methods revealed a large diversity of strains although some clusters predominated. More than 80% of the strains produced several exoenzymes, possessed pyoverdin and showed haemolytic activity, and all except one showed serum resistance. All strains were susceptible to silver and more than 80% to mercury and boron, but all were resistant to iodine. PMID- 1425728 TI - Evaluation of a chemiluminometric immunoassay for detection of Chlamydia trachomatis in the urine of male and female patients. AB - A chemiluminometric immunoassay (Magic Lite Chlamydia) for detection of Chlamydia trachomatis antigens in first-void urine samples was compared with cell culture using urogenital swabs from 221 men and 242 women. The rate of isolation of Chlamydia trachomatis was 23.5% in men, nearly 80% of whom had symptoms of urethritis, and 8.3% in women, in whom both cervix and urethra samples were tested. In urine sediments from men and women respectively the chemiluminometric assay showed a sensitivity of 80.8% and 70%, a specificity of 97% and 95%, a positive predictive value of 89.4% and 58.3%, and a negative predictive value of 94.3% and 97.2%. Discrepancies between results obtained with the chemiluminometric assay and cell culture were resolved using two polymerase chain reaction techniques to test urogenital samples. The detection of Chlamydia trachomatis in urine samples with the chemiluminometric assay was confirmed to be superior for screening symptomatic men with urogenital infections than women as a lower prevalence population. PMID- 1425729 TI - Review of nocardial infections in France 1987 to 1990. AB - On the basis of the numbers of Nocardia strains referred to the National Reference Center for Mycoses and Antifungal Agents (NRC), Institut Pasteur, Paris, in the period from 1987 to 1990, it was estimated that between 150 and 250 cases of nocardiosis are diagnosed in France each year. A total of 63 clinical isolates were referred to the NRC and identified as Nocardia asteroides (66.7%), Nocardia farcinica (23.8%), Nocardia brasiliensis (3.2%), Nocardia otitidiscaviarum (4.8%) and Nocardia carnea (1.5%). Nocardia asteroides accounted for 71.4% of pulmonary infections, 80.0% of central nervous system infections and 80.0% of systemic infections. Patients infected with Nocardia farcinica died in 57.1% of cases, compared with 17.6% of patients infected with Nocardia asteroides. Corticosteroid therapy represented a significant factor in mortality. Isolates of Nocardia asteroides revealed variable resistance, whereas isolates of Nocardia farcinica were resistant to most antimicrobial agents. Only amoxicillin/clavulanic acid, imipenem, cefoxitin, kanamycin, amikacin, minocycline and vancomycin showed activity against both species. Nocardiosis caused by Nocardia farcinica may be a growing problem because of the relatively high incidence in AIDS patients and the resistance of this species to most antimicrobial agents. PMID- 1425730 TI - Quantitative assay for testing susceptibility of HIV isolates to zidovudine and sCD4 (178)-PE40. AB - A quantitative coculture assay is described for determining susceptibility of HIV 1 isolates to zidovudine and sCD4 (178)-PE40 (a 60 kDa hybrid protein consisting of the gp120 binding region of CD4 linked to the translocation and ADP ribosylation regions of Pseudomonas aeruginosa exotoxin). The assay was relatively simple to perform and gave highly reproducible results often within three to five days. IC50 values of zidovudine for HIV-1 strains isolated from two AIDS patients and an asymptomatic seropositive individual were in the range 0.001 0.002 mumol. Isolates obtained after six months of zidovudine treatment had zidovudine IC50 values of 0.01-0.5 mumol. All isolates were equally sensitive to sCD4 (178)-PE40 (IC50 1-5 micrograms/ml). HIV-1 activation in the chronically infected cell line U-1 was inhibited by sCD4 (178)-PE40 but not by zidovudine. PMID- 1425731 TI - Clinical evaluation of a new lipid-based delivery system for intravenous administration of amphotericin B. AB - In a retrospective study a new lipid-based delivery system for administration of amphotericin B was evaluated in 26 treatment courses in 22 patients. Amphotericin B was given by infusion diluted in either the lipid solution (1 mg/kg/d; 13 courses) or dextrose (0.92 mg/kg/d; 13 courses). No differences were noted in the serum pharmacokinetics. Fever or rigors were observed in 6 of 13 courses in the conventional amphotericin B group versus none in the lipid amphotericin B group (p = 0.007). Four of 13 courses of treatment were discontinued due to adverse effects in the conventional amphotericin B group compared to none in the other group (p = 0.048). In the lipid amphotericin B group the decrease in creatinine clearance was significantly lower on the fourth day of treatment (p = 0.04) and significantly fewer patients had a decrease of more than 25% in creatinine clearance on the sixth day (4/12 vs 9/11 p = 0.02). These preliminary findings suggest that this lipid amphotericin B formulation is well tolerated with few nephrotoxic effects. PMID- 1425732 TI - A case of prolonged urinary tract infection caused by Mycobacterium fortuitum. AB - A case of prolonged urinary tract infection caused by Mycobacterium fortuitum in a 56-year old female patient is reported. The infection, which was resistant to therapy with conventional antituberculous agents, responded well to a combination of trimethoprim, sulfamethoxazole and doxycycline. PMID- 1425733 TI - Effect of subinhibitory concentrations of cefamandole and cefuroxime on adherence of Staphylococcus aureus and Staphylococcus epidermidis to polystyrene culture plates. AB - The ability of cefamandole and cefuroxime to inhibit adherence of staphylococci to polystyrene culture plates was tested in an in vitro assay using eight strains each of Staphylococcus aureus and Staphylococcus epidermidis. The results indicated that subinhibitory concentrations of cefamandole and cefuroxime altered the adherence ability of both staphylococcal species, inhibition of adherence being more marked in the presence of cefamandole. It may be important to consider antiadherence properties in association with bactericidal activity when selecting agents for antibiotic prophylaxis. PMID- 1425734 TI - Evaluation of a monoclonal antibody for detection of Helicobacter pylori in a direct immunofluorescence test. AB - A monoclonal antibody was developed for detection of Helicobacter pylori in gastric tissue sections in a direct immunofluorescence test. On a comparison of the immunofluorescence test with standard methods for detection of Helicobacter pylori, i.e. culture, the urease activity test and histological examination of tissue sections, using 158 biopsy specimens, 30 specimens were positive in all methods and 64 negative. In the remaining cases comparison was not possible because either immunofluorescence (29 specimens) or the standard methods (16 specimens) gave ambiguous results. The direct immunofluorescence test may have potential as an alternative to standard methods, but further testing in a defined patient population is necessary. PMID- 1425735 TI - Detection of hepatitis B virus DNA in chronic carriers by the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to detect hepatitis B virus DNA (HBV DNA) in serum samples of 104 chronic HBV carriers. Of 22 patients positive for both HBV surface (HBsAg) and HBVe (HBeAg) antigens, seven were positive for HBV DNA on dot blot hybridisation, and all 22 positive in the PCR. Of 41 HBsAg positive patients who had antibodies against HBeAg (anti-HBe), only three were positive for DNA-HBV on dot blot hybridisation, however DNA was detected in 30 of them with the PCR. Similarly, of 41 individuals with antibodies against HBsAg (anti-HBs), 23 yielded positive results in the PCR technique, although dot blot hybridisation detected HBV-DNA in only one patient. These results indicate that while serological and conventional DNA hybridisation assays are not sensitive enough to determine the infectivity of HBV chronic carriers, PCR is an accurate method for establishing the status and progression of disease in these patients. PMID- 1425736 TI - Choroiditis and meningitis in experimental murine infection with Listeria monocytogenes. AB - In a study of central nervous system involvement in experimental listeriosis 27 Swiss CD1 mice were inoculated subcutaneously with Listeria monocytogenes. Systemic infection developed, as shown by the isolation of Listeria monocytogenes and histopathological lesions in the spleen and liver. In the central nervous system a mixed inflammatory infiltration in the ventricular system, especially in the choroid plexus, and leptomeningitis were the most relevant lesions. Inflammatory lesions were associated with the presence of Listeria monocytogenes, as demonstrated by a positive anti-Listeria monocytogenes immunoperoxidase reaction within phagocytic cells. It is suggested that choroiditis and meningitis developed as a consequence of hematogenous dissemination of Listeria monocytogenes within mononuclear phagocytes and penetration of these cells into the ventricular system through the choroid plexus. PMID- 1425737 TI - In vitro susceptibility of Haemophilus influenzae to cefaclor, cefixime, cefetamet and loracarbef. AB - The susceptibility of 2,212 Haemophilus influenzae isolates cultured in UK clinical laboratories in 1991 was determined for four orally-administered beta lactam drugs. These isolates included 1,893 ampicillin-susceptible, 191 beta lactamase-positive and 128 ampicillin-resistant, beta-lactamase-negative Haemophilus influenzae. While 150 (6.8%) isolates were resistant to cefaclor (MIC > or = 16 mg/l) and 85 (3.8%) to loracarbef, all were inhibited by < or = 2 mg/l cefetamet and < or = 1 mg/l cefixime and were therefore susceptible to these agents. Ranges and modes of inhibition zone diameters and MICs indicated that the susceptibility of a variable proportion of the 191 beta-lactamase-positive isolates to cefaclor, loracarbef and cefetamet was reduced compared with the fully susceptible population. In contrast, a major reduction in susceptibility to all four antimicrobial agents was seen among the 128 ampicillin-resistant (MIC 1 64 mg/l) beta-lactamase-negative isolates such that these accounted for 53% and 67% of the total number of organisms resistant to cefaclor and loracarbef respectively. In addition, 23 of 25 isolates inhibited only by > or = 1 mg/l cefetamet and all eight inhibited only by > or = 0.5 mg/l cefixime showed this type of resistance to ampicillin. Results indicate the importance of detecting non-beta-lactamase-mediated resistance to ampicillin and any concomitant diminished susceptibility to other beta-lactam drugs. PMID- 1425738 TI - Antimicrobial activity of ten macrolide, lincosamine and streptogramin drugs tested against Legionella species. AB - RP59500, a semisynthetic pristinamycin combination, and 14 other antimicrobial agents were tested against 108 Legionella strains. Of the ten macrolide, lincosamine and streptogramin agents tested, the new streptogramin RP59500 ranked seventh in order of activity against Legionella pneumophila on the basis of MIC90 results as follows: clarithromycin = 14-OH clarithromycin (MIC90 0.12 mg/l) > roxithromycin > erythromycin = tylosin = virginiamycin > RP59500 (MIC90 1 mg/l) = azithromycin > dirithromycin > clindamycin (MIC90 8 mg/l). Of all 14 drugs tested in this study, rifampicin was the most potent with an MIC90 of 0.008 mg/l. In this retrospective study of Legionella strains (1981-1990 isolates), we observed no trend toward resistance to the agents investigated. PMID- 1425739 TI - In vitro antimicrobial activity of the new antibiotic vermisporin. AB - The antimicrobial activity of vermisporin, a new antibiotic produced by fermentation of the fungus Ophiobolus vermisporis, was tested in vitro. Vermisporin inhibited 90% of Bacteroides fragilis and other Bacteroides spp. at 1 microgram/ml (range 0.25-1 micrograms/ml). Clostridium perfringens were inhibited by 1 microgram/ml (range 0.25-2 micrograms/ml). Vermisporin inhibited 90% of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus, at 0.5 micrograms/ml (range 0.12-0.5 micrograms/ml). Vermisporin MICs for group A, B, C, F and G streptococci were < 1 microgram/ml when tested in Haemophilus Test Medium but > or = 8 micrograms/ml in the presence of blood. Vermisporin MICs for Enterobacteriaceae, Pseudomonas aeruginosa and Haemophilus influenzae exceeded 64 micrograms/ml. Inhibited organisms had MBCs 16- to 32-fold above the MICs. PMID- 1425740 TI - In vitro activity of L-627 against anaerobic bacteria. AB - The in vitro activity of L-627 against 370 anaerobic bacterial strains including anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of piperacillin, cefoxitin, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol. L-627, imipenem, meropenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested. L-627 had in vitro activity similar to that of the other carbapenems tested. PMID- 1425742 TI - Ultrasonographic evaluation of Legg-Calve-Perthes disease based on sonoanatomic criteria and the application of new measuring techniques. AB - This study attempts an ultrasonographic classification of Legg-Calve-Perthes disease according to sonoanatomic and sonometric criteria. Four stages, similar to standard radiological staging, could reproducibly be found in 29 patients with unilateral disease. The stages could be significantly differentiated according to descriptive sonoanatomic criteria and partially newly introduced sonographic measurements, including epiphysis-metaphysis-index and acetabulum-epiphysis distance. Sonographic evaluation of Perthes hips is a simple and standardised procedure, which can serve to stage and monitor the course of the disease and hence reduce the amount of X-ray exposure and treatment costs. PMID- 1425741 TI - Fatal septicemia due to a toxigenic strain of Corynebacterium diphtheriae subspecies mitis. PMID- 1425743 TI - Initial stage of Legg-Calve-Perthes disease: comparison of three-phase bone scintigraphy and SPECT with MR imaging. AB - Twenty-one patients with initial stage Legg-Calve-Perthes (LCP) disease were examined by three-phase bone scintigraphy, single photon emission scintigraphy (SPECT), and magnetic resonance (MR) imaging. On dynamic study, increased activity was present in the epiphysis or the growth plate in 39%; the corresponding figure for blood-pool images was 94%. Pinhole images demonstrated the lateral stripe of revascularization in 57% of patients. Decreased signal intensity in the epiphysis on T1-weighted images proved to be the most sensitive indicator of epiphyseal necrosis on MR imaging and was absent in only 10% of the cases. The subchondral fracture occurred in 62% (including the above 10% of cases), identified by T1-weighted image. Cartilaginous hypertrophy, detected by T1-weighted image, had a high incidence (81%). Joint effusion was identified on T2-weighted images in 90% of patients. The cross-sectional views provided by SPECT and MR imaging permits a better appreciation of the extent of epiphyseal necrosis in LCP disease. PMID- 1425744 TI - The role of ultrasound and isotope scanning in the management of irritable hips. AB - Patients (n = 181) with the irritable hip syndrome were reviewed. Four of these were found to have Perthes disease and 3 cases had septic arthritis. Ultrasonography provides accurate information as to the presence or absence of an effusion in children with an irritable hip syndrome. The likelihood of a positive result is higher in the early course of the disease process (i.e. within 3 days). Bone scanning, if done routinely will help in the early diagnosis of Perthes disease. Recurrence of the symptoms occurred in 18% of patients and most of them were within 12 months of the first onset of symptoms. PMID- 1425745 TI - Fracture of the carpal scaphoid: frequency and distribution in a well-defined population. AB - The incidence, location, and type of scaphoid fractures found in a well-defined population is described. Fractures of the carpal scaphoid (n = 442) were identified during an eight-year period, of which 19 (5%) were nonunions. At the initial radiographic examination the fractures were visible on PA views in 70% of the cases (true lateral 10%, scaphoid view neutral 77%, scaphoid view ulnar deviated 73%, and scaphoid view with the X-ray tube tilted 30 degrees distally 71%). Among inhabitants living in the Odense Municipality (population at risk 170648 in 1983 to 174948 in 1989) 222 males and 51 females (age range 9-87 year) sustaining scaphoid fractures during a seven-year were period used for computation of incidences. During the survey, there was an average annual incidence of scaphoid fracture of 8 per 100000 females, and 38 per 100000 males. All patients (except a 9-year-old male) were aged 10 years or over. In the age group 10-14 years there was an average annual incidence of 3 per 100000 females, and 39 per 100000 males. Average annual incidence per 100000 inhabitants of carpal scaphoid fractures according to the location was proximal 6, middle 15, and distal (fractures of the tuberosity included) 2. Average annual incidence per 100000 inhabitants of carpal scaphoid fractures according to type was transverse 7, horizontal oblique 9, vertical oblique 1, avulsion/fracture of the tuberosity 5, and not stated 1. PMID- 1425746 TI - Magnetic resonance imaging of the brain in idiopathic hypoparathyroidism: a case report. PMID- 1425748 TI - Mediastinal metastases of infradiaphragmatic malignancies. AB - Mediastinal lymph node metastases from infradiaphragmatic malignancies are reported to be a rare occurrence. The results of previous studies have been based on the evaluation of chest radiographs. In this study we retrospectively reviewed the chest and abdominal computed tomography examinations of 50 such patients. Of these, 25 had renal cell carcinoma and the remainder, other genitourinary or gastrointestinal carcinomas. The major nodal groups involved in the mediastinum were the right paratracheal in 41 cases, subcarinal in 31, paraesophageal in 26, and aortopulmonary in 25. Hilar nodes were involved in 21 cases. In the abdomen, para-aortic and or retrocrural adenopathy was present in 29 cases. Of 21 patients with pulmonary metastases, only 12 cases were associated with ipsilateral hilar lymphadenopathy. Supraclavicular lymphadenopathy occurred in only 8 patients. These results suggest that spread of infradiaphragmatic malignancies to the mediastinum occurs primarily by extension from the retrocrural and para-aortic nodes into the thoracic duct and then by antegrade flow in the thoracic duct and its collaterals, with retrograde flow from these channels to the mediastinal nodes. PMID- 1425747 TI - High-resolution computed tomography in cystic fibrosis. AB - The sensitivity of high-resolution computed tomography (HRCT) in identifying the pulmonary lesions of cystic fibrosis (CF) was evaluated. Thirty-nine patients (16 males, 23 females; mean age 19.1 years) were examined by chest HRCT. According to Shwachman and Kulczycki criteria, the clinical score of the patients ranged from 40 to 95, thus covering most possible variations of lung disease severity. All the patients presented diffuse thickening of bronchial walls, expression of the characteristic CF bronchial inflammation. Bronchiectases were the second most common lung lesions: discrete dilatation of bronchi was observed in 87% of cases; the localization, pattern and extent of bronchiectasis were accurately detected by HRCT. Pleural thickening and hilar adenopathy were frequently identified (in 64% and 82% of the patients, respectively). Bronchoceles were seen in 64% of the patients; atelectasis (33%) and subpleural bullous dystrophic emphysema (28%) were observed less frequently. On HRCT, the localization of the disease processes within the secondary pulmonary lobule was possible in all patients. In agreement with international literature, the identification of these lesions confirms HRCT as the more sensitive technique for early visualization and location of the manifestations of CF bronchopathy. A larger range of experience coming from a systematic use of HRCT in chronic inflammatory lung diseases would increase our knowledge of pathogenetic processes and allow improvement of therapeutic perspectives. PMID- 1425749 TI - Giant true aneurysm of an aortocoronary bypass graft: a rare cause for a mediastinal mass. PMID- 1425750 TI - Ruptured aneurysm of an aberrant right subclavian artery: CT and angiographic findings. PMID- 1425751 TI - Erectile dysfunction: timing of spectral wave-form analysis in the assessment of the function of the cavernosal arteries. AB - Color Doppler ultrasound seems to be an accurate method to evaluate vascular erectile function, in particular the arterial supply of the penis. Because of its relative noninvasiveness and easy performance, it has to precede more invasive evaluation (cavernosography and invasive angiography). Combination of wave form pattern analysis with peak systolic velocity measurements allows differentiation between arterial and venous insufficiency. Fifty-one patients suffering from erectile dysfunction, were examined with use of color Doppler ultrasound. Nine had adequate vascular function with good penile tumescence. However, during these adequate (late) stages of tumescence, peak systolic velocity fluctuated significantly. We conclude that in the late stages of tumescence, velocity measurements are not reliable as a parameter of arterial function. PMID- 1425752 TI - An unusual case of renal involvement in non-Hodgkin lymphoma. PMID- 1425753 TI - Sonographic findings in infants with suspected necrotizing enterocolitis. AB - During a three-year period, 27 infants with clinical signs of necrotizing enterocolitis (NEC) underwent ultrasonography; 22 of these infants also had abdominal radiographs within a few hours. Sonographically, portal venous gas (PVG) was seen in 10 and intestinal pneumatosis without PVG in 8 infants. Six children underwent laparotomy within 24 hours after ultrasonography and showed evidence of recent NEC. Three other children, laparotomized weeks later were found to have intestinal strictures as signs of previous NEC. None of the patients died from NEC. Nine infants without abnormal gas distribution did not develop overt NEC. With respect to PVG, sonography is able to support the tentative diagnosis of NEC prior to radiography. However, absence of PVG does not exclude NEC. PMID- 1425754 TI - Pseudomembranous colitis: an ultrasound diagnosis. PMID- 1425755 TI - Radiographic indicants of adult celiac disease assessed by double-contrast small bowel enteroclysis. AB - The number of folds and lumen diameter of the proximal jejunum and distal ileum were retrospectively measured in 40 double-contrast small bowel enteroclysis studies of patients with a biopsy-proven diagnosis of adult celiac disease (ACD) and in 46 healthy control subjects. For both parameters an inverse radiographic pattern was found in celiacs compared to control subjects, in whom the number of folds and lumen calibers are physiologically greater in proximal jejunum than in the distal ileum. Mean differences in the jejuno-ileal number of folds (-7.1) and lumen calibers (-1.3 cm.) were in fact negative in ACD patients, in whom the values of both the parameters are less in the proximal jejunum than in the distal ileum. Particularly, the sign of "reversal of jejuno-ileal caliber" was both sensitive and specific for diagnosis of ACD in this retrospective series. Double contrast small bowel enteroclysis can play an important role in excluding or confirming the presence of ACD, provided that an assessment of reproducibility and a prospective re-evaluation of operative characteristics of such radiographic signs are performed. PMID- 1425756 TI - Computed tomography of retroperitoneal duodenal rupture in blunt abdominal trauma. AB - Two cases of retroperitoneal duodenum rupture following an upper abdominal blunt trauma are reported. Computed tomography (CT) demonstrates at best extraintestinal fluid and air in the retroperitoneum, especially if acquisition in right lateral decubitus is possible. Drawbacks of the method are also reviewed. PMID- 1425757 TI - Defecography and anorectal manometry. AB - In a prospective study anorectal manometry was performed in 160 consecutive patients who were referred for defecography. Leakage of contrast material of standardized viscosity, the anorectal angle (ARA), anal resting pressure (Pr) and squeeze pressure (Ps) were measured and analyzed. This was done to investigate the role of ARA on rectal continence during defecography and to investigate whether relevant findings of manometry can be predicted from findings at defecography as part of the diagnostic work-up in selected patients in order to avoid manometry in these patients. The ARA was of significance in maintaining rectal continence for the contrast medium (P = 0.008). With increasing leakage, Pr and Ps decreased significantly (P less than 0.001). In all fully incontinent patients (n = 36) Ps was distinctly below normal values. Manometry can be avoided in these patients if the level of Pr is not important for therapeutic strategy. PMID- 1425758 TI - Magnetic resonance imaging of the gastrointestinal tract: investigation of baby milk as a low cost contrast medium. AB - After the incidental observation of the high signal intensity of the upper GI tract in a nourished baby, we tested eight baby milks; five different fresh commercial milks, one sweetened and condensed and two lyophilized milks in order to compare their ability to contrast MR images. The images were obtained with a 1.5 T magnet whereas the "in vitro" water proton relaxation time (T1 and T2) measurements were carried out at 0.5 T. After having selected the most effective lyophilized product, that was prepared according to the manufacturer's instructions, a group of 23 adult patients, 17 males and 6 females, with a mean age of 55.8 years (range 37 to 71 years) were examined. Thirteen patients had gastric cancer and ten patients had rectal or rectosigmoid junction tumors. The most effective imaging sequence was a spin-echo T1.w. After oral intake of milk a good contrast of the stomach, with sufficient distribution in the duodenum and the very proximal bowel, was achieved in all 13 patients with gastric cancer, as was a good depiction of the rectum and the recto-sigmoid junction after enema achieved in the 10 patients with rectal cancers. Disadvantages of lyophilized milk as a contrast agent are due to partial intestinal absorption, inhomogeneous distribution and irregular intestinal passage, whereas a clear advantage of lyophilized milk as a contrast agent is its good acceptance and palatable, inexpensive and non invasive properties. Because of these limitations lyophilized milk cannot be considered a real oral contrast medium but it can enhance MR imaging of the upper abdomen, and mainly of the lower GI tract in infants and adults. PMID- 1425759 TI - Acute cholecystitis: ultrasonographic staging and percutaneous cholecystostomy. AB - Experience in the treatment of acute cholecystitis with percutaneous cholecystostomy in 29 high-risk and elderly patients is reported. The treatment group included 14 men and 15 women, 21 of whom were over 70 years of age. The suspected clinical diagnosis of acute cholecystitis was confirmed in all cases by ultrasonography (accuracy: 95.6%). The percutaneous cholecystostomy was successful in 27 of 29 cases and these patients had a sudden improvement in their clinical condition; failure of the procedure was due in one patient to dislodgement of the catheter and in another patient to the guide-wire slipping out of the gallbladder. Six patients complained of pain radiating to the right shoulder which disappeared within 30-60 minutes after the procedure. Twenty-three of the 27 patients subsequently underwent elective cholecystectomy. In 22 patients the ultrasonographic findings were compared with the histology; thus enabling us to establish an ultrasonographic staging of acute cholecystitis related to the seriousness of the disease. Percutaneous cholecystostomy is the treatment of choice in high-risk patients, in the elderly, as well as in young patients with impending perforation. PMID- 1425760 TI - Serious or fatal complications after inadvertent administration of ionic water soluble contrast media in myelography. AB - The consequences of the inadvertent administration, by the intrathecal route, of ionic contrast media instead of iopamidol in seven subjects are reported. The ionic compounds were diatrizoate, iodamide and ioxitalamate. The outcome was fatal in three out of seven subjects, and it depended on the type and the dose of the administered contrast agent. The serious or fatal reactions observed are a tragic confirmation of the predictive power of neurotoxicity data obtained in animal studies with various iodinated water-soluble compounds. The margin of safety, represented by the ratio of LD50 i.ce. in mice to clinical dose in humans, both normalized to bodyweight, appears to reliably reflect the risk of toxic reactions after intrathecal administration of iodinated contrast agents. PMID- 1425761 TI - A Golgi-related structure remains after the brefeldin A-induced formation of an ER-Golgi hybrid compartment. AB - Brefeldin A (BFA) has previously been shown to block protein transport from the endoplasmic reticulum (ER), to cause the redistribution of Golgi components to the ER, and to change profoundly the morphology of the Golgi apparatus. In order to quantitate the effects of this drug on the morphology of the ER and the Golgi apparatus in HeLa cells, the numerical, surface and volume densities of these organelles were determined by stereological means. We found that in cells treated with BFA (5 micrograms/ml) clusters of vesicles and tubules, often located near transitional elements of the ER, replaced the Golgi apparatus. The numerical density of these clusters in cells treated with BFA for 30 min or 4.5 h is similar to that of Golgi complexes and Golgi-related clusters in control cells. The surface density of the vesicles and tubules contained in these clusters is about 50% of that represented by Golgi elements in control cells. Concomitantly, a corresponding increase in the surface density of the ER-Golgi hybrid compartment was observed. This hybrid compartment contained Golgi-specific enzymes effecting modifications of N-linked oligosaccharides and the transfer of O-linked sugars. Antibodies recognizing different subcompartments of the Golgi apparatus or the intermediate compartment, labeled vesicles and tubules of the Golgi-related clusters. Applying low doses of BFA allowed for the dissection of the disassembly of the Golgi apparatus into at least two phases. At very low doses (10-20 ng/ml) the numerical density of vesicles in the clusters increased up to 4-fold above control, while the surface density did not markedly change, suggesting that vesiculation of the Golgi cisternae had occurred. Fusion of Golgi elements with the ER seemed to occur only at doses of BFA higher than 20 ng/ml. Contrary to observations on other cell types, removal of BFA from HeLa cell cultures resulted in a rather slow reformation (1-2 h) of the Golgi complex, which allowed us to observe several intermediate stages in this process. During this time period an ER was restored which no longer contained Golgi-specific O glycosylation functions. Our results demonstrate that BFA does not simply cause the disappearance of the Golgi apparatus by fusion with the ER, but instead clusters of vesicles and tubules remain that contain Golgi-specific markers. PMID- 1425762 TI - Golgi proteins persist in the tubulovesicular remnants found in brefeldin A treated pancreatic acinar cells. AB - Brefeldin A (BFA) blocks protein export from the endoplasmic reticulum (ER) and causes dismantling of the Golgi cisternae with relocation of resident Golgi proteins to the ER in many cultured cell lines. We examined the effects of BFA on Golgi organization and the distribution of Golgi markers in the rat exocrine pancreas. Immediately after BFA addition, Golgi stacks began to disorganize and Golgi cisternae to vesiculate, and by 15 min no intact Golgi cisternae remained. However, even after prolonged BFA incubation, clusters of small vesicles surrounded by transitional elements of the ER persisted both in the Golgi region and dispersed throughout the apical cytoplasm. These vesicles were morphologically heterogeneous in the density of their content and in the presence of cytoplasmic coats. Immunogold labeling demonstrated that some vesicles within the clusters contained gp58, a cis Golgi marker, and some contained alpha mannosidase II, a middle/trans Golgi marker in this cell type. Neither marker was detected in the rough ER by immunogold or immunofluorescence labeling. When AlF4- was added during BFA treatment some of the vesicles in the clusters appeared coated. When microsomes were subfractionated into Golgi (light) and rough ER (heavy) fractions on sucrose density gradients, greater than 65% of alpha mannosidase II and galactosyltransferase activities were found in light fractions (1.14-1.16 g/ml) in both control and BFA-treated lobules. In both cases equally low enzyme activity was recovered in heavier fractions (1.2-1.23 g/ml) containing RNA and alpha-glucosidase activity. However, 5 to 8% of the total recovered RNA consistently codistributed with the Golgi enzyme peak. These results indicate that BFA rapidly inhibits secretion and causes dismantling of the Golgi stacks in pancreatic acinar cells, but clusters of vesicles consisting of bona fide Golgi remnants persist even with prolonged exposure to BFA. Many of the vesicles contain Golgi markers by immunolabeling. By cell fractionation Golgi membrane enzyme activities are recovered in equal amounts in light (Golgi) fractions in both controls and BFA-treated specimens. These findings indicate that in the exocrine pancreas there is a dissociation of BFA's effects on the exocytic pathway: there is a block in transport and Golgi organization is disrupted, but remnant Golgi vesicles and tubules persist and retain Golgi membrane antigens and enzyme activities. PMID- 1425763 TI - Presence of Golgi remnant membranes in the cytoplasm of brefeldin A-treated cells. AB - Brefeldin A (BFA) rapidly blocks secretion, induces disassembly of the Golgi complex and causes a redistribution of Golgi components into the endoplasmic reticulum (ER). In addition to these effects on the exocytotic pathway, BFA has been shown to induce fusion of endosomal membranes with the trans-Golgi network in some cell types. To better understand the mechanism through which BFA disrupts the exocytotic traffic, we have examined its effects on the ultrastructural organization of the Golgi complex. Within minutes of exposure to BFA, the Golgi cisternae were fragmented into a number of small tubules and vesicles, many of which had a non-clathrin coat on their cytosolic surface. In addition, a complex structure consisting of anastomosing tubules and associated vesicles appeared in the cytoplasm of cells incubated with BFA for 10 min or longer. These tubular networks were permanent, distinct structures separated from the ER cisternae. They contained cis, middle, and trans Golgi proteins as well as the lipid analogue C5-DMB-ceramide. Furthermore, secretory proteoglycans en route through the Golgi were retained in the lumen of the tubular networks. As judged by the endocytosis of cationized ferritin, endosomes do not contribute to the formation of these tubular networks. Reassembly of the Golgi complex after BFA incubation involved fragmentation and reorganization of the tubular networks as well as fusion with vesicles budded from the ER. We conclude that although in the presence of BFA the bulk of Golgi membranes are induced to fuse with the ER, as indicated by the detection of Golgi markers in this organelle, a fraction of these membranes remain in the cytoplasm organized as Golgi remnants. PMID- 1425764 TI - Evidence that globular Golgi clusters in mitotic HeLa cells are clustered tubular endosomes. AB - By conventional electron microscopy we observed in mitotic HeLa cells the structures termed Golgi clusters by Lucocq et al. (J. Cell Biol. 104, 865-874 (1987)) and interpreted by them as clusters of vesicular remnants of the Golgi apparatus. Golgi clusters consist of tubular and vesicular profiles about 50 nm in diameter, sometimes associated with larger 250 nm vesicles. When cultures of HeLa cells were incubated for 60 min or 120 min with medium containing high specific activity horseradish peroxidase (HRP) at 10 mg/ml we found that the membrane-bound compartments in the Golgi clusters in mitotic cells contained heavy deposits of HRP reaction product. Neither interphase nor mitotic HeLa cells contain an endogenous peroxidase activity. We concluded that Golgi clusters are an endocytic compartment and confirmed this by showing that Golgi clusters could be labeled with two other endocytic tracers--bovine serum albumin conjugated to colloidal gold and transferrin conjugated to HRP. When cultures were incubated with HRP for only 15 min most of the Golgi clusters in the mitotic cells were either unlabeled or consisted of a mixture of HRP-labeled and unlabeled profiles. Since during mitosis endocytosis is inhibited this was the expected result. When interphase HeLa cells were incubated with Brefeldin A (BFA), the Golgi apparatus disassembled and immunofluorescence microscopy showed that 1,4 beta galactosyltransferase had relocated to the endoplasmic reticulum. When cells in the presence of BFA and lacking the Golgi apparatus were allowed to endocytose HRP and then entered mitosis, typical HRP-labeled Golgi clusters were seen in the mitotic cells. It is therefore highly unlikely that these structures contain membrane derived from the Golgi cisternae that are sensitive to BFA, including in HeLa cells those containing galactosyltransferase. Finally, we found that interphase HeLa cells incubated with okadaic acid contain structures that are morphologically indistinguishable from Golgi clusters but can be labeled by endocytic tracer. Taken together, this evidence indicates that most, if not all, of the membrane-bound compartments in Golgi clusters are tubular early endosomes. PMID- 1425765 TI - Cell-adhesive properties of streptavidin are mediated by the exposure of an RGD like RYD site. AB - The interaction of streptavidin with various cell systems was studied using fluorescent derivatives of the protein. The native unprocessed form of streptavidin bound to cells at low levels and in a nonspecific manner. In contrast, both the truncated "core" streptavidin (the commercially available form) and the biotin-blocked unprocessed protein bound to cells in enhanced levels and in a specific, saturable manner. This suggests that the binding of biotin or cleavage of the terminal portion(s) of the native protein molecule causes conformational changes which lead to the exposure of sites which presumably interact with cell surface receptors. Peptide inhibition studies demonstrated that the majority of binding to cells appears to be dependent on RGD like specificity, suggesting that the GRYDS sequence of the streptavidin molecule may exhibit such specificity. Indirect immunofluorescence assays revealed that the protein is associated mainly with the cell surface. Moreover, streptavidin was demonstrated to compete with specific monoclonal antibodies to the RGD binding site on the GpIIbIIIa integrin of activated platelets, thus suggesting that streptavidin may facilitate binding to ubiquitous cell-surface adhesion receptors via RGD mimicry. PMID- 1425766 TI - Migration of polarized epithelial cells through permeable membrane substrates of defined pore size. AB - We have observed that cells of various epithelial lines exhibit the ability to migrate through permeable membrane substrates containing 3.0 microns pores. Scanning and transmission electron microscopic observations of Vero C1008 and Caco-2 cell lines grown on polycarbonate membranes containing 3.0 microns pores revealed extensive penetration of the filter and the establishment of virtually complete monolayers on the opposing surface. The migration of MDCK cells was also observed to occur under the same conditions; however, the extent of MDCK cell growth on the opposing surface was significantly less than observed for Vero C1008 and Caco-2 cells. Morphological differences were apparent between cells growing on the upper and lower faces of the filter membrane, although cells growing on both surfaces exhibited a polarized phenotype. The cells which invaded the filter were collected and maintained by serial passage. The passaged cells exhibited morphological differences and an altered rate of differentiation in comparison to the parental cell type, suggesting that the invasive cells represent a variant of the parental cell population. Studies using filters of different pore sizes indicated that cellular migration also occurs through pores of 2.0 microns diameter, but not through 1.0 micron (or smaller) pores. These observations have significant implications for studies involving the growth of epithelial cells on permeable membrane substrates containing large pores. PMID- 1425767 TI - Sea urchin coelomic fluid agglutinin mediates coelomocyte adhesion. AB - The sea urchin Paracentrotus lividus coelomic fluid was found to contain agglutinin which agglutinates animal erythrocytes and promotes adhesion of autologous coelomocytes. Hemagglutinating activity depended upon the presence of calcium ions and was relatively heat-stable. Through a combination of methods including ammonium sulfate precipitation and both size exclusion and ion exchange chromatographies, we purified the anti-rabbit agglutinating factor. The intact agglutinin migrates as a single band with an apparent M(r) of over 200,000. Three distinct protein bands with a calculated M(r) of 174,000, 137,000, and 76,000, respectively were observed under reducing conditions. The purified agglutinin strongly promoted the in vitro adhesion of autologous coelomocytes. PMID- 1425768 TI - The expression and synthesis of the band 3 protein initiates the formation of a stable membrane skeleton in murine Rauscher-transformed erythroid cells. AB - While the temporal sequences of the synthesis and assembly of membrane skeletal proteins has been studied during erythroid maturation, relatively little is known about the events which initiate the assembly of membrane skeleton at the early stages of mammalian erythroid commitment. To investigate the early events that initiate the assembly of the membrane skeleton in mammalian erythroid cells, we have studied the synthesis and assembly of membrane skeletal proteins in murine Rauscher erythroleukemia virus-transformed cells. These cells are blocked in differentiation at around the early progenitor (burst forming unit-erythroid, BFUe) cell stage but can be induced to differentiate in vitro. Pulse-labeling studies reveal that Rauscher cells actively synthesize alpha spectrin, beta spectrin, ankyrin and band 4.1 proteins. However, the synthesis of the band 3 protein and its mRNA are barely detectable in these cells. The peripheral membrane skeletal components assemble only transiently in the membrane skeleton and turn over rapidly, resulting in about 20-fold lower steady state levels than are found in mature erythrocytes. Upon induction with erythropoietin and dimethyl sulfoxide, the mRNA level and synthesis of band 3 are increased about 50-fold. In contrast, the synthesis of spectrin, ankyrin and band 4.1 is increased only about 1.5 to 2.0-fold. However, after induction, the fraction of these proteins assembled on the membrane is increased, their half-lives on the membrane are nearly doubled with a concomitant 4 to 5-fold increase in their steady-state levels. These results suggest that the synthesis of peripheral membrane proteins is detected at the earliest stages of erythroid commitment and increases only slightly during further differentiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425769 TI - Assembly of a tail-less mutant of the intermediate filament protein, vimentin, in vitro and in vivo. AB - Recent reports on the possible contribution of the non-alpha-helical carboxy terminal domain ("tail") of type III intermediate filament (IF) proteins to IF assembly have been controversial. To examine the importance and role of this domain, we have therefore engineered a Xenopus laevis vimentin cDNA to code for a tail-less polypeptide and have used it in combination with prokaryotic and eukaryotic expression systems. Here we show that tail-less vimentin, isolated from transfected bacteria (Escherichia coli), when used for assembly in vitro, forms normal-looking, loosely packed IFs. By viscometry we demonstrate that this tail-less vimentin assembles at an even higher rate and into longer IFs than wild type vimentin. In vivo, i.e., by forced expression in transfected type III IF free cultured epithelial cells, tail-less vimentin was also recovered in short fibrillar structures, in rodlets and in small as well as large spheroidal aggregates ("granules") that did not reveal any IF substructure. Surprisingly, however, spheroidal aggregate structures formed from the tail-deleted vimentin, were seen not only in the cytoplasm but also in the nucleus, indicating a role of the tail in higher order organization and compartmentalization of the vimentin IF system. PMID- 1425770 TI - Macromolecular structure of reassembled neurofilaments as revealed by the quick freeze deep-etch mica method: difference between NF-M and NF-H subunits in their ability to form cross-bridges. AB - Neurofilament (NF) structure and ability to form cross-bridges were examined by quick-freeze deep-etch mica and low-angle rotary-shadow electron microscopy in NFs purified from bovine spinal cord and reassembled in various combinations of NF subunits. When NFs were reassembled from triplet proteins, NF-L, NF-M and NF H, they were oriented randomly and often fragmented, but their elongated filaments (12-15 nm wide) and the cross-bridges (4-5 nm wide) connecting them were similar in appearance to those of isolated bovine NFs or in vivo rat NFs. Projections extended from the wall of the core filament in almost the same pattern as the cross-bridges and were the same in width and interval (minimum interval, 20-25 nm) as the cross-bridges. Projections were more conspicuous when core filaments were separated by 60 to 80 nm or more, while cross-bridges were more conspicuous when core filaments were close to each other. Projections or cross-bridges extended bilaterally at intervals of 20 to 25 nm where core filaments expanded and formed a network between filaments which were far from one another. When NFs were reconstructed from NF-L alone, only core filaments appeared, the same width as the filaments of triplet NFs. The core filaments were occasionally in almost direct contact with each other, with no projection or cross-bridge. When NFs were reassembled from NF-M alone or NF-L + NF-M, although NF-M core filaments were shorter and slightly thinner than NF-L + NF-M core filaments, both had projections, and both had cross-bridges, but cross-bridges were less evident. Cross-bridges were almost the same in width as those of triplet NFs, but significantly shorter and much less frequent although the minimum interval was the same, and core filaments were not attached to each other. In contrast, when NFs were reconstituted from NF-H alone or NF-L + NF-H, both had conspicuous projections and cross-bridges, similar to those of triplet NFs. Thus, when NFs contained NF-H, they formed frequent cross-bridges and long projections with extensive peripheral branching. When NFs contained NF-M but no NF-H, they tended to form cross-bridges, and to form projections that were shorter and straighter and without peripheral branching. That is, there appears to be a significant difference between NF-M and NF-H in ability to form cross bridges and thus in interaction with adjacent NFs. PMID- 1425771 TI - A unique tubulin antiserum attenuates the rate of poleward chromosome movement in anaphase. AB - An antiserum against tubulin, NS20, was previously shown to specifically attenuate both fast axonal transport in vivo (Johnston, K. M. et al., Brain Res. 385, 38-45 (1986)) and in vitro (Johnston, K. M. et al., Cell Motil. Cytoskel. 7, 110-115 (1987)) and flagellar motility (Goldsmith, M. et al., Cell Motil. Cytoskel. 20, 249-262 (1991)). We hypothesized that NS20 blocked motility by binding to a multifunctional motor binding domain on the microtubules (MTs), or axonemes. Here we have examined the effect of microinjecting NS20, at metaphase, into dividing PtK2 cells. Plotting chromosome separation (CS) as a function of time, we report here that CS rates for anaphase A (chromosome-to-pole movement) were reduced by approximately 50% relative to uninjected controls. CS rates for anaphase B (spindle pole elongation) were unaffected by the NS20 antiserum. The inhibition of CS rate during anaphase A by NS20 was significantly greater than the inhibition caused by a control antitubulin serum (PC5). Two possible mechanisms underlying NS20's inhibition of CS during anaphase A were considered. NS20 could block the binding of a kinetochore-associated motor to kinetochore MTs (kMTs) or, alternatively, NS20 could stabilize kMTs against depolymerization. Our results favor the first alternative. In a cold-induced depolymerization assay, NS20 had no selective stabilizing effect on MTs. Moreover, we show that NS20 can selectively block the binding of a well characterized MT-associated motor (kinesin) to MTs, in vitro. These results suggest that NS20 may be defining a unique tubulin binding domain common to the motors underlying vesicle transport, flagellar motility, and chromosome movements during anaphase A. PMID- 1425772 TI - Evidence for reversible, non-microtubule and non-microfilament-dependent nuclear translocation of hsp90 after heat shock in human fibroblasts. AB - A monoclonal antibody (29A) directed against rat liver heat shock protein M(r) 90,000 (hsp90) was produced. By Western immunoblotting of cytosols prepared from several different tissues and species, 29A was shown to specifically recognize only one band with M(r) approximately 90,000. Localization of hsp90 in human gingival fibroblasts was studied using the 29A antibody by indirect mono- and double-staining immunofluorescence and confocal laser scanning microscopy. The distribution was compared to that of the glucocorticoid receptor (GR) and various cytoskeletal structures. Cells were analyzed in interphase and mitosis under basal culture conditions, after heat shock and after microtubule and microfilament depolymerization, sometimes combined with heat shock. A major part of hsp90 immunoreactivity was diffusely distributed throughout the interphase cytoplasm, but a weak nuclear staining with non-stained nucleoli was also present, however, only detectable after methanol and not after formaldehyde/Triton X-100 fixation. Heat shock induced a time-dependent translocation of hsp90 from the cytoplasm to the cell nucleus reaching a plateau after 15 h. This compartment shift was reversible and also occurred in the absence of intact microtubules or intact microfilaments. PMID- 1425773 TI - The phosphoinositide pathway of lymphoid cells: labeling after permeabilization by alveolysin, a bacterial sulfhydryl-activated cytolysin. AB - An improved method allowing incorporation of [3H]myo-inositol into the phosphoinositide pool of human lymphoid cells is described. The procedure devised involves cell permeabilization with a thiol-activated membranolytic toxin, alveolysin, and optimization of the phosphoinositide labeling and extraction. In these conditions 4 to 10% of the added [3H]myo-inositol is found intracellularly and half of this amount (2-5%) is incorporated into the phosphoinositide pool in only 1 h as compared to the classical 0.2 to 0.3% incorporation obtained after 10 to 20 h. The integrity of coupling between receptors and phospholipase C was assessed by the inositol phosphate production after cell stimulation by various agonists. PMID- 1425774 TI - Immunolocalization of secretogranin II, chromogranin A, and chromogranin B in differentiating human neuroblastoma cells. AB - In order to obtain further insights into the expression of the known markers of secretory neuroendocrine dense core organelles, secretogranin II (SgII), chromogranin A (CgA), and chromogranin B (CgB) during neuronal differentiation, the immunolocalization of these proteins was studied by means of double immunofluorescence in both undifferentiated and retinoic acid-differentiated SH SY5Y human neuroblastoma cells. The majority of undifferentiated cells was not immunolabeled for all three proteins. In the majority of differentiated cells, a clearly punctate SgII immunolabeling indicative of the presence of secretory organelles was present in the Golgi region, at the cell periphery, along the neurites and in growth cones. Only relatively few of the SgII-immunolabeled cells were also immunolabeled for CgA and CgB, and in a single cell the three proteins were not always present in the same organelles. These results, obtained in a cultured cell line, confirm the not necessarily parallel distribution of SgII, CgA, and CgB observed in different neuroendocrine tissues and suggest that SgII may be the best marker of human neuroblastoma cell differentiation. PMID- 1425775 TI - In vitro differentiation of mouse embryo chondrocytes: requirement for ascorbic acid. AB - Chondrocytes enzymatically dissociated from 13-day-old mouse embryo tibia grow in monolayer culture with a fibroblast-like phenotype and express high levels of type I collagen. Chondrogenesis can be induced by transferring the adherent cells in suspension culture and maintaining them in the constant presence of mouse embryo extract. Round shaping of the cells and formation of multicellular aggregates rapidly follow the passage in anchorage-independent conditions. Cell differentiation is evidenced by a marked decrease in the level of type I collagen and by the induction of type II collagen which accumulates when ascorbic acid is included in the culture medium. The addition of the vitamin also triggers the aggregated chondrocytes to organize their extracellular matrix giving rise to a structure closely resembling the in vivo developing cartilage. PMID- 1425776 TI - Different proliferative potential of rat and pig hepatocytes in pure primary culture and coculture. AB - In the present study we have compared the growth potential of hepatocytes from rats and pigs and the influence of cocultivation between these hepatocytes and the rat liver epitheloid cell line RL-ET-14. Proliferation, i.e., DNA synthesis, was detected by autoradiography after exposure to [3H]thymidine. Rat hepatocytes cultured at low cell density showed a very low basal growth and responded to epidermal growth factor (EGF) and insulin by a considerable increase in DNA synthesis after 48 h leading to a labeling index (LI) of 33%. Cocultivation with RL-ET-14 cells almost completely blocked the basal as well as the growth factor stimulated proliferation of the rat hepatocytes. In contrast, pig hepatocytes cultured alone showed a much greater growth potential (basal: LI 11%; insulin/EGF:LI 67%) than rat hepatocytes and were further stimulated by cocultivation (basal: LI 39%; insulin/EGF: LI 89%). Density-dependent inhibition of cell growth was less pronounced with pig hepatocytes. Even after reaching confluency, they showed further strong proliferation in pure as well as in cocultures whereas the LI of the rapidly growing clone RL-ET-14 decreased to 40%. Use of conditioned medium from RL-ET-14 cells did not mimic the growth inhibition of rat hepatocytes in coculture indicating that no soluble growth inhibitors produced by the epitheloid cells are responsible for this effect. In particular, the differences between rat and pig hepatocytes in coculture are not simply due to production of TGF-beta by the epitheloid cells since the hepatocytes from both species were inhibited by TGF-beta to a similar extent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425777 TI - The lethal prune/Killer-of-prune interaction of Drosophila causes a syndrome resembling human neurofibromatosis (NF1). AB - The eye color mutant prune (pn) of Drosophila melanogaster shows a lethal interaction with the Killer-of-prune (K-pn) allele of the abnormal wing disc (awd) locus. The awd gene is the Drosophila homologue of the mammalian tumor metastasis gene nm23, and it has been postulated that pn encodes a protein with similarity to a GAP, a GTPase-activating protein. Such GAPs potentially control Ras-like proteins, which are important molecular switches. However, there is only a low sequence homology with the genes for human GAP and neurofibromatosis (NF1), and with yeast IRA1 and IRA2, and there is no evidence for the functional significance of this homologization. I now show that pn mutations lower the concentrations of larval pteridines, and that this phenomenon is enhanced by two orders of magnitude by the lethal interaction between pn and awdK-pn. These gradual effects on the pteridin concentrations indicate a corresponding drop of the pools of free GTP, and favor the involvement of GTP-binding proteins. In addition, cytology reveals a considerable hypertrophy of the neuroglia and the perineurium of the larval brain. Furthermore, the lymph glands of the larvae are highly abnormal and form melanotic (pseudo)tumors upon ageing of the larvae. These pseudotumors consist predominantly of lamellocytes which are part of the cellular defence system of Drosophila. These observations most likely indicate hyperactivity of a Ras-like protein which becomes manifest in cell types equivalent to the cell types affected by human neurofibromatosis (NF1). Thus, it is very suggestive to regard the synthetic lethal system prune/Killer-of-prune as the Drosophila model for human neurofibromatosis. PMID- 1425778 TI - Cancer treatment monitoring with fluorine-18 2-fluoro-2-deoxy-D-glucose and positron emission tomography: frustration or future. PMID- 1425779 TI - Improved positron emission tomography quantification by Fourier-based restoration filtering. AB - Positron emission tomography (PET) images are characterized by both poor spatial resolution and high statistical noise. Conventional methods to reduce noise, such as local weighted averaging, produce further deteriorations in spatial resolution, while the use of deconvolution to recover resolution typically amplifies noise to unacceptable levels. We studied the use of two-dimensional Fourier filtering to simultaneously increase quantitative recovery and reduce noise. The filter was based on inversion of the scanner's measured transfer function, coupled with high frequency roll-off. In phantom studies, we found improvements in both "hot" and "cold" sphere quantification. Compared with ramp only filtering, improvements in hot spot recovery for the highest accuracy filter averaged 13.6% +/- 6.6% for spheres larger than 15 mm; improvements in cold spot recovery averaged 30.7% +/- 4.7%. At the same time, the noise was reduced by a factor of 3 compared with randomly filtering. Fourier-based image restoration filtering is thus capable of improving both accuracy and precision in PET. PMID- 1425780 TI - Motor stimulation response by technetium-99m hexamethylpropylene amine oxime split-dose method and single photon emission tomography. AB - We applied the technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) split dose method in order to evaluate the feasibility of assessing cerebral blood flow (CBF) changes with single photon emission tomography (SPET) during a motor activation task. Eleven normal subjects were studied using the Tomomatic 564 (Medimatic, DK). Five subjects were studied twice at rest and 6 subjects at rest and during a motor task performance (finger opposition movements). A total of 28 mCi of 99mTc-HMPAO was injected in 2 doses with a 1:3 ratio. The first scan was obtained after injection of 7 mCi at rest in all subjects. The second scan was obtained a few minutes later, after injection of the remaining dose (21 mCi), under similar resting conditions or during a motor task performance. The mean brain uptake was proportional to the amount of tracer injected and to the acquisition time for both the first scan (5263 +/- 1266 counts x mCi x min) and the second (5034.4 +/- 966 counts x mCi x min). The grey/white matter ratio was 1.67 +/- 0.019 and 1.67 +/- 0.097 for the two scans, respectively. A three-way analysis of variance (ANOVA) for repeated measure showed no significant effects of side, slice and region of interest (ROI) on the CBF in the 5 subjects studied twice at rest, and the mean regional CBF change was -0.2% +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425782 TI - Reliability of first-pass radionuclide determination of cardiac output in the upright position at rest and during exercise. AB - The reliability of non-invasive determination of cardiac output using first-pass radionuclide cardiography at rest and during exercise in the upright position was evaluated in 20 patients with coronary artery disease. Cardiac output values ranged from 2.97 to 5.99 l/min at rest and from 5.08 to 10.82 l/min during exercise. Cardiac output results obtained by the radionuclide method were compared with those derived from the thermodilution technique performed simultaneously. The mean difference between the two techniques was 0.02 l/min at rest and -0.34 l/min during exercise; the limits of agreement (mean +/- 1.96 SD) were -1.29 to 1.33 l/min and -1.97 to 1.29 l/min, respectively, indicating an acceptable level of agreement. A high reproducibility of the radionuclide technique was found, with a mean difference between determinations by two observers of 0.03 l/min at rest and 0.21 l/min during exercise, the corresponding limits of agreement being -0.75 to 0.81 l/min and -0.79 to 1.21 l/min, respectively. With the aid of a variance component analysis of two determinations by each of four observers, 95% confidence intervals of +/- 10% at rest and +/- 12% during exercise were computed for the radionuclide cardiac output measurements. The observer variation was most pronounced for the part of the cardiac output determination related to measurement of left ventricular equilibrium activity during exercise. First-pass radionuclide cardiography is a reliable method for determination of cardiac output in cardiac patients at rest and during exercise in the upright position. PMID- 1425781 TI - Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201 in patients with coronary artery disease: a comparative dual-isotope study. AB - To characterise the clinical usefulness of serial myocardial scintigraphy with iodine-123 phenylpentadecanoic acid (IPPA) in comparison with thallium-201, dual isotope investigations were performed in 41 patients with angiographically documented coronary artery disease. Both tracers were administered simultaneously during symptom-limited ergometry. Planar scintigrams were acquired immediately after stress, and delayed imaging was performed after 1 h for IPPA and 4 h for 201Tl. Scintigrams were evaluated both qualitatively and quantitatively using a newly developed algorithm for automated image superposition. Initial myocardial uptake of both tracers was closely correlated (r = 0.75, p < 0.001). Both tracers also revealed a similar sensitivity for the identification of individual coronary artery stenoses > or = 75% (IP-PA: 70.0%, 201Tl: 66.3%, P = NS) with identical specificity (69.8%). The number of persistent defects, however, was significantly higher with IPPA (P = 0.021), suggesting that visual analysis of serial IPPA scintigrams may overestimate the presence of myocardial scar tissue. On the other hand, previous Q wave myocardial infarction was associated with a decreased regional IPPA clearance (29% +/- 11% vs 44% +/- 11% in normal myocardium, P < 0.05). The data indicate that serial myocardial scintigraphy with IPPA is essentially as sensitive as scintigraphy with 201Tl for the detection of stress induced perfusion abnormalities. Quantitative analysis of myocardial IPPA kinetics, however, is required for the evaluation of tissue viability. PMID- 1425783 TI - The use of technetium-99m hexamethylpropylene amine oxime labelled white blood cells to detect subclinical inflammation of the heart after cardiopulmonary bypass in children with congenital heart disease. AB - Ten children (6 boys and 4 girls, aged 1-9 years old) underwent operations with a cardiopulmonary bypass, and the technetium-99m hexamethylpropylene amine oxine (99mTc-HMPAO) labelled white blood cell (WBC) heart scans were used to detect postoperative leukocyte infiltration in the hearts. The results showed that 80% (8/10) of the cases had subclinical inflammation in the hearts (grading of WBC scans > or = score 2), and a positive correlation (R = 0.77) was noted between the severity of the inflammation (grading of the WBC scans) and the duration of the cardiopulmonary bypass in the operations. Another control group (9 boys and 2 girls, aged 2-13 years old) underwent operations without a cardiopulmonary bypass, and subclinical inflammation of hearts was demonstrated in only 1 case (9%) by the 99mTc-HMPAO labelled WBC scans (grading of WBC scans < score 2) after the operations. There was a significant difference (P < 0.001, by a Wilcoxon rank sum test) based upon the severity of the ischaemic heart damage in the two groups. In our preliminary conclusions, the 99mTc-HMPAO labelled WBC heart scans may provide non-invasive and directly discernible evidence of subclinical inflammation in the heart due to a transient ischaemic state during a cardiopulmonary bypass, even if the clinical symptoms and signs of carditis are not apparent. PMID- 1425784 TI - Gallbladder response to a second dose of cholecystokinin during the same imaging study. AB - Patients on total parenteral nutrition or after prolonged fasting may require treatment with cholecystokinin (CCK) prior to hepatobiliary imaging. Some may also require evaluation of gallbladder (GB) contractility, and the need for a second dose of CCK may arise. It is not clear whether gallbladder function can be adequately evaluated with CCK when a previous CCK dose had already been administered. We studied ten normal subjects to evaluate GB response to a second CCK injection. The subjects received 20 micrograms/kg sincalide in a 3-min infusion prior to administration of technetium-99m disofenin. They then received an identical sincalide dose at 60 min postinjection, and imaging was continued for another 30 min to quantify GB contraction. Gallbladder ejection fraction (GBEF) values ranged from 42-98% (mean: 71.5 +/- 19%). Pretreatment with CCK does not preclude GB contraction evaluation with a second dose of CCK. Expected GBEF values are similar to those obtained with single CCK injections. PMID- 1425785 TI - Detection of rhinorrhoea by cisternography in combination with single photon emission tomography, following lumbar injection of iodine-123-labelled albumin. AB - Eight patients were examined. Seven had verified rhinorrhoea and six had had one or more episodes of pneumococcal meningitis. In four of the patients a fistula could not be visualized by computed tomography. All eight patients had injections of iodine-123-labelled albumin by lumbar puncture. Tomoscintigraphy (SPET) was performed 3, 6 and 8-9 h after injection. After 6-8 h we were able to demonstrate a fistula in seven of the patients with verified rhinorrhoea and the findings were confirmed by a subsequent operation. In one of the patients we were not able to visualize any leak of cerebrospinal fluid into the nasal cavity. This patient was not operated upon and we were not able to verify the findings in this patient. The operated patients all did well after the operation with no relapse of meningitis. In conclusion, SPECT-cisternography after intralumbar injection of iodine-123-labelled albumin is a valuable diagnostic tool for the detection of small fistulae in patients with rhinorrhea. PMID- 1425787 TI - Comparison of technetium-99m MAG3 kit formulations in Europe and the USA. PMID- 1425786 TI - Gamma scintigraphy in the evaluation of pharmaceutical dosage forms. AB - Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 oxide or erbium-170 oxide followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. PMID- 1425788 TI - Lawson Wilkins (1894-1963). PMID- 1425789 TI - Tetralogy of Fallot in three siblings: a familial study and review of the literature. AB - We report a family in which three out of four siblings had tetralogy of Fallot (TOF). The family history showed TOF in the daughter of a maternal cousin, while no other congenital heart diseases were discovered. Although no teratogenic environmental agent was discovered, the absence of parental consanguinity and the presence of another affected relative suggest multifactorial inheritance. Autosomal recessive inheritance cannot be ruled out. PMID- 1425790 TI - Predictive factors for the effect of gonadotrophin releasing hormone analogue therapy on the height of girls with idiopathic central precocious puberty. AB - The factors influencing the final height of central precocious puberty patients treated with gonadotrophin releasing hormone (GnRH) analogues remain a critical issue. This study compares the predicted final height before and after GnRH analogue therapy to identify predictive factors for final height. Fourteen girls with idiopathic central precocious puberty were treated with a GnRH analogue. All had an active non-regressive form before therapy, full and permanent suppression of oestrogenic activity during therapy (duration greater than 2 years, 3.1 +/- 0.3 years, mean +/- SEM), and the pubertal pituitary-ovarian axis had normalized in all of them 1 year after the cessation of therapy. The mean predicted final height increased from 152 +/- 1.8 cm before therapy to 162.2 +/- 1.2 cm (P less than 0.01) at the last evaluation performed 4.5 +/- 0.3 years after the onset of therapy. The mean gain in predicted final height between the onset of therapy and the last evaluation was 10.2 +/- 1.1 cm. It was correlated with the following data recorded at the onset of therapy: bone age advance over chronological age (r = 0.66, P less than 0.02), predicted final height at the onset of therapy (r = 0.76, P less than 0.001), and the difference between the target height and the predicted height at onset of therapy (r = 0.76, P less than 0.001). We conclude that GnRH analogue therapy is more likely to improve final height prognosis in girls who initially present with a markedly advanced bone age and a great difference between their target and predicted heights. Both these parameters reflect the severity of the disease at diagnosis. PMID- 1425791 TI - Liver dysfunction and acute cardiocirculatory failure in children. AB - We report 15 children who developed transient liver dysfunction related to hepatic ischaemia. All patients had cardiocirculatory failure 24 h before the onset of liver injury (day 1). Peak serum values of transaminases occurred between day 1 and day 3: SGOT (mean: 759 IU/l, range: 150-4400); SGPT (418 IU/l, 95-2547). Transaminase values decreased rapidly and normalised from day 6 to day 10. Minimum values of prothrombin test (PT) occurred on day 1 (31%, 10-70) and 13/15 patients had a PT less than 50% (27%, 10-44). PT values normalized from day 3 to day 10. Hypoglycaemia was present in 8/15 patients on day 1. Liver dysfunction improved after correction of the circulatory failure. These results confirm that transient hepatic dysfunction, probably as a consequence of hepatic hypoperfusion, may occur frequently in children after acute circulatory failure. We conclude that the diagnosis of ischaemic liver injury or shock liver syndrome in children can be made on clinical and biochemical criteria, and that liver biopsy is unnecessary. PMID- 1425792 TI - Mediastinal germ cell tumour associated with Klinefelter syndrome. A report of case and review of the literature. AB - A 14-year-old boy with Klinefelter syndrome (KS) and a large mediastinal tumour is presented. Human chorionic gonadotropin and oestradiol were markedly increased. An attempt at radical resection was performed. Histological examination revealed a malignant germ cell tumour of mixed histologic pattern composed of choriocarcinoma and components of mature teratoma. Four courses of cisplatin, bleomycin, and etoposide were given. The patient is without any evidence of tumour recurrence 20 months after diagnosis. A review of the literature revealed another 40 cases of primary mediastinal germ cell tumour (PMGCT) associated with KS. Compiled data from larger series demonstrate that at least 8% of male patients with PMGCT have KS, 50 times the expected frequency. In contrast to PMGCT in patients without KS, all tumours were of nonseminomatous histology, and the average age was considerably lower, Tumours in prepubertal boys were associated with precocious puberty. PMID- 1425793 TI - Polymerase chain reaction-amplification of urease genes: rapid screening for ureaplasma urealyticum infection in endotracheal aspirates of ventilated newborns. AB - Ureaplasma urealyticum infection has been considered to play an important role in the development of bronchopulmonary dysplasia (BPD) in premature infants. Since standard culture methods of U. urealyticum are difficult to perform, new rapid and sensitive methods are needed to detect lung infection of ventilated newborns. Here we describe the polymerase chain reaction as a rapid method to screen endotracheal aspirates for ureaplasma infection. Urease-specific sequences could only be detected in 1 out of 36 ventilated newborns. The procedure described in this paper may facilitate further studies to determine the role of U. urealyticum in development of BPD. PMID- 1425794 TI - Tick-borne encephalitis in a 3-month-old child. AB - Tick-borne encephalitis has not been reported in infants younger than 12 months of age. We report a 3.5-month-old child with a serologically proven tick-borne encephalitis. The infant had a history of a tick bite 3.5 weeks before the first symptoms of encephalitis appeared. The family lives in an endemic area of the disease. There were no prodromal signs and the course of the disease was monophasic. In an endemic area, prophylactic treatment with hyperimmunoglobulin after a tick bite should be considered even in very young infants, but in most children active immunization is probably not necessary because of infrequent exposure. Active immunization is still recommended after the 1st year of life. PMID- 1425795 TI - Unsuspected rheumatic heart underlying group B streptococcal endocarditis at the age of 20 months. AB - The case is reported of a 20-month-old girl admitted to our centre for group B streptococcal endocarditis who died of complete atrioventricular block after a week of treatment. There was no history pointing to the presence of a heart disorder. Necropsy disclosed the surprising existence of a vast rheumatic carditis involving essentially the aortic and mitral valves, with bacterial superinfection of the former. The double rheumatic and infectious lesion in such a young patient with infective pseudo-aneurysms of the sinuses of Valsalva makes this an exceptional case. PMID- 1425796 TI - Pulmonary hypertension complicating a ventriculo-atrial shunt. AB - The use of ventriculo-atrial shunts for CSF diversion in developing hydrocephalus has become rare because of the risk of chronic thrombo-embolism and subsequent pulmonary hypertension associated with an unfavourable prognosis. However, there remains a group of patients in whom ventriculo-atrial shunts have been inserted in the past. In this group, complications can occur after many years. We report on a 13-year-old girl with pulmonary hypertension caused by chronic thrombo embolism from a ventriculo-atrial shunt. PMID- 1425797 TI - Statural growth in Williams-Beuren syndrome. AB - The spontaneous growth of 165 patients (75 girls and 90 boys) with Williams Beuren syndrome was analysed in a mixed longitudinal and cross-sectional manner. Mean (+/- 1 SD) length at birth was 48.2 +/- 2.6 cm in girls (n = 52) and 49.0 +/ 3.0 cm in boys (n = 65). Intrauterine growth retardation (length below -2 SD of the normal population) was present in 35% of the girls and 22% of the boys. Poor growth was noted during the first 2 years of life. Until age 9 years in girls and 11 years in boys, mean growth followed the 3rd percentile. A pubertal growth spurt with normal growth rate was seen at age 10 years in girls and 13 years in boys, i.e. 1 to 2 years earlier than normal. Menarche also occurred earlier than normal at a mean age of 11.6 +/- 1.5 years (n = 28). Mean adult height was 153.9 +/- 6.9 cm in girls (n = 17) and 168.2 +/- 6.9 cm in boys (n = 27), approximately corresponding to the 3rd percentile in both sexes and correlating with the genetic height potential (target height). The mean deficit of adult height compared to target height was 10.2 cm in girls and 9.1 cm in boys. Skeletal development progressed at an approximately normal rate in both sexes. PMID- 1425798 TI - Simultaneous measurement, using flow cytometry, of radiosensitivity and defective mitogen response in ataxia telangiectasia and related syndromes. AB - In a retrospective study, peripheral blood mononuclear cells from 13 patients with known ataxia telangiectasia (AT) (Louis Bar syndrome, McKusick #20890) were irradiated with different doses of X-rays prior to stimulation with phytohaemagglutinin. Mitogen response and cell cycle progression were assessed by two-parameter 5-bromo-2'-deoxyuridine/Hoechst--ethidium bromide flow cytometry. Compared to age-matched controls, AT cells show a severely defective mitogen response in both unirradiated and irradiated cells. Following irradiation with 1.5 Gy, AT cells exhibit significantly greater accumulations of cells in the G2 phase of the first cell cycle than controls. The ratio between the number of cells accumulated in the first cycle G2 phase and the growth fraction provides a clear distinction between AT and control cultures. In addition, two patients with microcephaly, normal intelligence, immunodeficiency, chromosomal instability and risk for lymphoreticular malignancies (Seemanova syndrome) and two patients with the Nijmegen breakage syndrome (both syndromes are listed as McKusick #25126) also exhibit very poor mitogen response and moderately increased G2 phase accumulations after X-irradiation. The simultaneous assessment of radiosensitivity and mitogen response in a single cell kinetic assay provides a speedy and accurate classification of cells of AT and AT-related syndromes. PMID- 1425799 TI - Carrier detection in X-linked adrenoleukodystrophy by determination of very long chain fatty acid levels and by linkage analysis. AB - Diagnosis of X-linked adrenoleukodystrophy is based upon demonstration of high levels of very long chain fatty acids. More recently, in addition to biochemical analysis, closely linked DNA probe St14 has been used for prenatal diagnosis in informative families. Identification of heterozygotes is particularly important, both in order to specifically address only carrier females to prenatal diagnosis, and because appropriate dietary therapy is now available to treat those heterozygotes presenting with neurological symptoms. We report two pedigrees in which carrier detection was performed by a combination of biochemical and molecular genetic analysis. Such approach should allow extremely high accuracy in carrier detection. PMID- 1425800 TI - Serum levels of carboxyterminal propeptide of type I procollagen in healthy children from 1st year of life to adulthood and in metabolic bone diseases. AB - Type I collagen is the major component of bone matrix; circulating carboxyterminal propeptide of type I procollagen (P-I-CP) levels reflect type I collagen synthesis in tissues and may be an useful index to investigate bone metabolism. We measured P-I-CP by a new radioimmunoassay in 300 healthy children and adolescents and in 40 healthy adults to provide reference data for P-I-CP values. In addition, 79 patients with diagnosed disorders of phospho-calcium metabolism (rickets, vitamin D deficient and vitamin D resistant, hyperparathyroidism, hypo- and pseudo-hypoparathyroidism, osteopenia) were evaluated. In the healthy subjects, serum P-I-CP values were higher in children than in adults; variations of P-I-CP levels were observed according to age and sexual maturation: higher values were found in the first years of life and during pubertal development; pubertal increase reflects the different timing of pubertal development in the two sexes. P-I-CP levels were increased in primary hyperparathyroidism and reduced in diseases related to impaired secretion or action of parathyroid hormone. Higher P-I-CP levels were found in vitamin D deficient and vitamin D resistant rickets. P-I-CP was reduced in anorexia nervosa and during chronic glucocorticoid treatment while it was increased in thyrotoxic osteoporosis. In idiopathic juvenile osteoporosis, P-I-CP values ranged from reduced to increased values. We conclude that P-I-CP may represent an additional biochemical marker of bone metabolism. Since age-related variations are present, reference data for the various ages are need for clinical application of this assay. PMID- 1425801 TI - High frequency oscillatory ventilation and extracorporeal membrane oxygenation in severe persistent pulmonary hypertension of the newborn. AB - We report on 50 term and near-term neonates (birth weight greater than 1800 g, gestational age greater than 33 weeks) with severe persistent pulmonary hypertension of the newborn (PPHN), referred to us from January 1987 to July 1991 after failure of maximum conventional treatment. All infants had paO2 less than 45 mm Hg when ventilated with peak inspiratory pressure greater than 38 cm H2O and FiO2 = 1.0, hence meeting entry criteria for extracorporeal membrane oxygenation (ECMO). High frequency oscillatory ventilation (HFOV) was tried in all patients. If sufficient oxygenation could not be achieved (paO2 less than 40 mm Hg for at least 2 h), ECMO therapy was begun, which was the case in 25 children. Neonates responding to HFOV (n = 25) were of a slightly younger gestational age (37.0 weeks vs 38.8 weeks, P less than 0.05), had higher Apgar scores and were less hypoxaemic before HFOV (paO2 36.6 mm Hg vs 28.8 mm Hg, P less than 0.01); during HFOV there was a significant rise in paO2 (greater than 150 mm Hg; P less than 0.001) and a fall in pCO2 to 21.6 mm Hg (P less than 0.001). Due to air leaks, which was the main complication of HFOV (52%), ECMO therapy had to be begun in two additional infants after an initial positive effect. HFOV tended to be successful in cases of primary PPHN, meconium aspiration and sepsis, but not in infants with lung hypoplasia as a result of diaphragmatic hernia or other reasons. Success or failure of HFOV could not be reliably predicted by any parameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425802 TI - Long-term low-dose cyclosporin A in steroid dependent nephrotic syndrome of childhood. AB - Therapy of steroid-dependent idiopathic nephrotic syndrome is often unsatisfactory. Since 1986 we have treated nine children (six male and three female), aged 3-16 years, with cyclosporin A (CsA) during 2.0-5.2 (median 3.1) years. All had minimal change disease on renal biopsy and had previously received cyclophosphamide. Mean daily dosage of CsA was 4.1 mg/kg (range 2.7-5.8) and mean whole blood trough level was 220 ng/ml (range 141-271). The relapse rate decreased from 3.4/patient year before CsA to 0.55 on CsA. Discontinuation of CsA or reduction below 2 mg/kg daily was always followed by a relapse. The overall relapse rate, including the period with very low-dose CsA, was 0.95/patient year. Four patients required additional low-dose alternate-day prednisone. Repeat renal biopsy showed minimal change disease in eight patients and focal segmental glomerulosclerosis in one; CsA-toxicity was mild in two and moderate in one. The latter was the only patient with slightly reduced glomerular filtration rate. Two boys with delayed puberty spontaneously matured and reached expected final height. We conclude that long-term low-dose CsA is very effective and steroid sparing. Its use is justified in selected patients, particularly in those with numerous relapses and in male patients before and during puberty, as long as renal function and CsA-toxicity are carefully monitored. PMID- 1425803 TI - Cortical visual impairment following bacterial meningitis: magnetic resonance imaging and visual evoked potentials findings in two cases. AB - Cortical visual impairment (CVI) following bacterial meningitis is a very uncommon complication. Two children with CVI following bacterial meningitis are reported. Bacterial agents were Haemophilus influenzae type B in one and meningococci in the other child. Both children showed only insufficient recovery from CVI, mental retardation and residual neurological symptoms. Flash visual evoked potentials (VEP) showed preserved cortical response at onset of CVI. Re evaluations several months later showed significantly reduced amplitudes, but normal latencies for P100. Thus, flash VEP does not allow prediction of visual outcome. MRI results have not been reported before. MRI at onset of diagnosis showed occipital parenchymal irregularities with enlarged sulci and subarachnoid spaces. Follow up MRI 15 months after onset of CVI in one patient showed marked atrophy of the occipital cortex, hyperintensities of the cortical white matter and no visible optic radiation. The MRI findings indicate hypoxic-ischaemic lesions in the border zone between the distribution of the great cerebral arteries. PMID- 1425804 TI - Follow up study of cow's milk protein intolerant infants. AB - Over a period of 4 years, 88 infants with cow's milk protein intolerance (CMPI) were followed prospectively in order to evaluate the persistence of CMPI and its relationship between either serum IgE levels or RAST results for cow's milk. After exclusion of lactose intolerance, two positive cow's milk elimination challenge tests were considered diagnostic for CMPI. At the age of 1, 2, 3 and 4 years respectively, 85%, 78%, 49% and 33% of the children still were cow's milk intolerant. Initial serum values of IgE greater than or equal to 10 kU/l indicated a late development of tolerance to cow's milk proteins. At the age of 4 years, 90% of infants with initial IgE levels less than 10 kU/l had become tolerant to cow's milk while this was the case for only 47% of infants with initial IgE levels greater than or equal to 10 kU/l. Initial RAST results for cow's milk bore no obvious relationship to outcome. PMID- 1425805 TI - Risks of alternative nutrition in infancy: a case report of severe iodine and carnitine deficiency. AB - A 7.5-month-old infant with failure to thrive, developmental delay, muscular hypotonia, a visible goitre and severe osteopenia is described. Laboratory examination revealed a markedly increased serum TSH with low free T4, severe iodine and carnitine deficiency. The infant was breastfed until the age of 2.5 months and was then given a mixture of almond extract in water. The mother is a strict vegan and the father a lactovegetarian. The nutritional intake of the child was severely depleted in calories (-46%), calcium (-73%) and iodine (-88%). The restrictive alternative nutrition was responsible for the various deficiency disorders. PMID- 1425806 TI - Recurrent haemolytic uraemic syndrome in a boy with focal and segmental glomerulosclerosis. PMID- 1425807 TI - Outcome of neonatal citrullinaemia. PMID- 1425808 TI - Disposition and metabolism of pravastatin sodium in rats, dogs and monkeys. AB - Pravastatin sodium (pravastatin) is a potent inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase, and was found to be highly effective in animals and humans, in lowering the plasma cholesterol level by inhibiting cholesterol synthesis selectively in the liver. In the present study the disposition and metabolism of pravastatin was studied in rats, dogs and monkeys using [14C]-labelled compound. The extent of absorption was approximately 70% in rats and 50% in dogs. Tissue distribution examined by both whole-body autoradiography and radioactivity measurement demonstrated that the drug was selectively taken up by the liver, a target organ of the drug, and excreted via bile mainly in unchanged form. Since pravastatin excreted by the bile was reabsorbed, the enterohepatic circulation maintained the presence of unchanged pravastatin in the target organ. The profiles of metabolites were studied in various tissues and excreta and a metabolic pathway of pravastatin was proposed. PMID- 1425809 TI - In vitro forecasting of drugs that may interfere with codeine bioactivation. AB - The O-demethylation of codeine (methylmorphine) into morphine is mediated by the polymorphic cytochrome P450 DB1 (P450 IID6). By means of in vitro screening in human liver microsomes we have studied the effect on codeine bioactivation of several drugs used as analgesics or as adjuvants for pain control. In microsomes from an extensive metabolizer subject, paracetamol (acetaminophen) and NSAIDs (acetylsalicylic acid, diclofenac, indomethacin, piroxicam, and pirprofen), benzodiazepines (chlordiazepoxide, clonazepam, diazepam, flunitrazepam, and midazolam), and anticonvulsants (carbamazepine and phenytoin) did not alter the reaction. There was marked inhibition of in vitro morphine production by neuroleptics (chlorpromazine, haloperidol, levomepromazine, and thioridazine), metoclopramide, and tricyclic antidepressants (amitriptyline, clomipramine, desipramine, imipramine, and nortriptyline). Enzyme kinetics showed competitive inhibition by neuroleptics (chlorpromazine Ki = 0.5 microM) and antidepressants (clomipramine Ki = 6.8 microM), which are substrates of the polymorphic monooxygenase. Due to the low affinity of codeine for P450 DB1 (Km = 100-200 microM), its bioactivation in extensive metabolizers, and thus its analgesic efficacy, is liable to vary greatly when it is combined with any drug that has a high affinity for the polymorphic isozyme. PMID- 1425810 TI - Bioconversion of netobimin pro-drug by gastrointestinal fluids of ruminants. AB - The biotransformation of netobimin (NTB) pro-drug by ruminal, abomasal and intestinal fluids of sheep and cattle was investigated under anaerobic conditions in vitro. No metabolic conversion of NTB was observed upon incubation with abomasal fluid or boiled samples of different gastrointestinal fluids. NTB pro drug was reduced and cyclised into albendazole (ABZ) and this further oxidized into ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2) by both sheep and cattle ruminal and ileal fluids. A zwitterion formulation of NTB produced a significantly greater amount of anthelminthically active ABZ metabolites (ABZ and ABZSO) than a trisamine salt formulation of the same compound. Although there was no difference in the total amount of products formed, both cattle ruminal and ileal fluids showed a greater oxidative capacity than sheep derived fluids. This was evidenced by the greater amounts of ABZSO recovered and by the resultant lower ratios of ABZ/ABZSO obtained with cattle fluids. PMID- 1425811 TI - Absorption of valproic acid from the gastrointestinal tract of the piglet. AB - Valproic acid is a commonly used drug for the treatment of epilepsy. Since valproic acid can only be given orally, its absorption from the gastrointestinal (GI) tract especially in patients with short bowel syndrome (SBS) and in neonates is important. The specific sites of absorption for valproic acid in the small intestine and colon have not been investigated. It is currently unknown whether these patients are able to absorb oral valproic acid sufficiently to maintain a therapeutic serum concentration. The primary objectives of the study were to: (a) determine the relative absorption of valproic acid from specific sites in the GI tract; and (b) investigate the influence of intestinal development on valproic acid absorption using the newborn piglet as a model. Two groups were studied: Group I included 5 piglets 18-21 days of age, and Group II included 5 piglets 1-3 days of age. A valproic acid solution was simultaneously perfused through 5 partitioned segments of the gastrointestinal tract: the duodenum, jejunum, ileum, right colon and left colon. Tritiated [3H] polyethylene glycol was co administered to monitor water movement across the GI mucosa. Following steady state, samples were collected from each segment, and analyzed by a specific enzyme-mediated immunoassay. The absorption rates (micrograms/min/cm) of valproic acid in Group I were as follows: 9.96 +/- 2.8 duodenum; 11.28 +/- 2.79, jejunum; 9.42 +/- 3.34, ileum; 10.88 +/- 3.35, right colon; 10.96 +/- 2.92, left colon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425813 TI - Metabolism of actisomide in the dog, monkey and man: a novel rearrangement of N dealkylated metabolites. AB - The metabolism of actisomide, a novel antiarrhythmic agent, was studied in the dog, monkey and man and was found to be more extensive in the monkey than in the dog or man. The major metabolites identified were a piperidinyl hydroxylated metabolite, the mono-N-dealkylated, cyclized and piperidine hydroxylated metabolite, and the cyclized and mono-N-dealkylated metabolite. Excretion of the parent drug was higher in urine than in feces in the dog, but in the monkey and man, urinary and fecal excretion of actisomide was similar. In all species the metabolites were primarily excreted in feces. PMID- 1425812 TI - Chronopharmacokinetics of Cyclosporine A in the Wistar rat following oral administration. AB - The pharmacokinetics of Cyclosporine A (CsA) was studied in male Wistar rats weighting 300 +/- 50 g trained to a 12:12 light-dark cycle. Oral administration (40 mg/kg) was performed at 1 of 4 different temporal stages: 09.00 h, 15.00 h, 21.00 h or 03.00 h (local time) i.e. 0200, 0800, 1400 or 2000 HALO (hours after light on). Blood samples were collected over 72-96 h after dosing, plasma was separated by centrifugation at 37 degrees C and stored frozen until assay, using radioimmunoassay (RIA). Two experiments were performed: the first with 4 groups of 48 rats and a non-specific polyclonal antibody (P-RIA); and the second with only 2 groups of 48 rats and a more specific monoclonal antibody (M-RIA). Plasma concentration data were evaluated with model-based linear pharmacokinetic concepts, with apparent zero-order or first-order absorption and n-exponential disposition (n = 1, 2 or 3): models MN0 or MN1. A compartment-independent approach was also conducted and led to area under the plasma concentration-time curve (AUC) and mean residence time (MRT) determinations. A comparison of the pharmacokinetic profiles across time of administration indicates that absorption, first-pass metabolism and tissue distribution of CsA in the rat are circadian dosing stage dependent. PMID- 1425815 TI - Pharmacokinetics of mitomycin C in patients after bolus injection and chemobolisation of the hepatic artery with Spherex starch particles. AB - The pharmacokinetics of mitomycin C after chemobolisation of the common hepatic artery by micronized Spherex starch particles (mean particle size 30 microns) were investigated in 5 cancer patients. Bolus injection and simultaneous occlusion of the artery lead to a significantly lower systemic circulation of mitomycin C in the blood vessel system than after bolus injection without chemobolisation. The plasma concentration-time curves showed lower values in the alpha-phase in the presence of Spherex (co = 743 ng/ml) than without starch particles (co = 987 ng/ml). Accordingly, the AUC values were significantly lower too (AUC = 28.6 micrograms/ml.h with Spherex and 39.7 micrograms/ml.h without Spherex), thus leading to a lower systemic bioavailability of the drug and a higher local bioavailability in the tumor region. Elimination of mitomycin from the central compartment was similar for both administrations (t1/2 = 27 min with Spherex and 28 min without Spherex) and showed the characteristic profile of the substance. The clinical picture showed a milder toxicity with a certain loss of side effects. These results indicate a significant and desirable change in the pharmacokinetics of mitomycin C during the distribution phase into the tissue of patients. PMID- 1425814 TI - Functional and dispositional tolerance develops during continuous cocaine exposure. AB - Despite the fact that high doses of cocaine are abused chronically, relatively little is known regarding the development of tolerance and/or sensitization under these circumstances. Therefore, male Sprague-Dawley rats were infused continuously i.v. for 10 days, at a rate of 150 mg/kg/day (0.1 mg/kg/min) with cocaine hydrochloride. Body weight, food and water consumption, urine and fecal excretion, as well as blood pressure, heart rate and stereotypic behavior were monitored daily. Blood samples were also drawn daily so that plasma could be analyzed for cocaine and BEG by gas chromatography/mass spectrometry. Severe body weight loss on days 1 through 4 was followed by a gradual return to pre-drug levels. In addition, cocaine's effects on food and water consumption and urine and fecal excretion, which were maximal by day 2, were imperceptible by day 5. Complete tolerance developed rapidly to the remarkable rise in blood pressure noted on the first day. However, tolerance did not develop to the cocaine-induced increase in heart rate. A profound decrease in heart rate was noted in some animals which was interpreted to be cardiotoxicity since these animals subsequently died. On the other hand, sensitization or intensification of behavioral stereotypy occurred during the first 2 days followed by complete tolerance to this effect by day 5. No withdrawal phenomena were noted 24 h after cocaine was abruptly withdrawn. Plasma concentrations of cocaine rose rapidly during the first day and remained elevated at a constant level until day 5. Then, a sharp decline in plasma levels occurred at day 6 which remained depressed for the duration of the infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425816 TI - Pharmacokinetics and metabolism of [3H]-pipethiaden in healthy volunteers. AB - Six healthy volunteers participated in a single-dose study of pharmacokinetics and metabolism of oral administration of [3H]-pipethiaden (1 mg). Plasma levels of total radioactivity, urinary excretion and metabolism were analyzed by liquid scintillation counting and radio-TLC. The mean peak plasma concentration of radioactive metabolites was 4.9 ng eq/ml, and the mean elimination half life was 11.5 h. 34% of radioactivity was recovered in 4 days in urine, with only 0.4% present as unchanged drug. Pipethiaden was extensively metabolized by S oxidation, N-demethylation, and N-oxidation. PMID- 1425817 TI - Mass spectrometric identification of urinary and plasma metabolites of 2-(6' carboxyhexyl)-3-n-hexylcyclohexylamine, a new antiaggregating agent. AB - The compound IBI-P-05006, 2-(6'-carboxyhexyl)-3-n-hexylcyclohexylamine, is an antiaggregating agent under development. IBI-P-05006 is an in vitro inhibitor of platelet aggregation. The biotransformation of this compound has been studied in the dog and rat. We present here a study on the metabolites of IBI-P-05006 found in dog and rat urine, and in dog plasma. Analyses were done by gas chromatography mass spectrometry. In dog urine 15 metabolites were identified. Some of them were also found in dog plasma and in rat urine. The unmetabolized drug was found only in plasma. 10 different hydroxylated metabolites were characterized. The hydroxyl groups were introduced in the hexyl chain in positions omega-4, omega-3, omega-2, omega-1 and omega. PMID- 1425818 TI - Nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of parkinsonian patients: analysis on the maintenance and the change of the original mode of treatment. AB - A nation-wide collaborative study to evaluate the long-term effects of bromocriptine in patients with Parkinson's disease was completed as described in the accompanying paper. The present study analysed the same data by paying attention to a group of patients who maintained the original mode of therapy and to a group of patients who changed the mode of treatment by adding levodopa or bromocriptine to the original drug. Surprisingly, 48 among 286 patients in a group of bromocriptine monotherapy maintained the original mode of therapy. This group has particular features of a short duration of illness and a low grade of Hoehn-Yahr's scale. It is noteworthy that this group of patients did not show wearing-off phenomenon. The effects of additional bromocriptine to levodopa for a 5-year period were analysed by comparing two groups of combination therapy and levodopa alone therapy maintained for 5 years, with 106 and 92 patients, respectively. Results were essentially the same as those obtained from the accompanying paper, i.e., in general, treatment by combination with bromocriptine may be more suitable than treatment by levodopa alone. In order to find the best timing of the combination of levodopa and bromocriptine, results of 3 groups were compared, i.e. a group of patients who started with bromocriptine alone and later added with levodopa (82 patients), a group of patients who maintained the combination for 5 years (106 patients) and a group of patients who started with levodopa alone and later added bromocriptine (27 patients). The best results were obtained in the group of 5-year combination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425819 TI - Primary combination therapy of early Parkinson's disease. A long-term comparison between the combined regimen bromocriptine/levodopa and levodopa monotherapy- first interim report. AB - The aim of this multicenter randomized prospective study in patients with early Parkinson's disease is to differentiate over a 4-year period between levodopa/benserazide monotherapy and the corresponding combination with bromocriptine by the assessment of motorial side effects, therapeutical benefit and fine motorial skills. Although there is circumstantial evidence, that partial substitution of levodopa by bromocriptine carries benefit in preventing late levodopa-specific side effects and delaying the declining therapeutical benefit, so far no knowledge has been available how levodopa and the corresponding combination with bromocriptine would compare on a long-term basis. Such study appears all the more important since there are experimental findings consistent with a neurotoxic effect of levodopa on the one hand and some 'protective' impact of bromocriptine on the other. As to the practical procedure of the comparison, all patients were first treated with a levodopa monotherapy for 3 months. This was a platform for the consecutive randomized splitting of the patients into two groups receiving either continuing levodopa therapy or combination therapy, based upon at least 40 +/- 10% substitution of levodopa by bromocriptine. The investigation methods included, besides the usual clinical rating scales (Webster, Zung, Hoehn and Yahr), an apparative test series, the so-called 'MLS', which allowed a sensitive and reliable assessment of fine motorial skills. The results of the first 3 months of treatment with levodopa monotherapy before the consecutive splitting into the two treatment regimens demonstrate that the randomization was successful and that there were no significant differences, that potentially might interfere with the drug-specific evaluation afterwards. The results of the substitution phase show that combined treatment permitted a mean reduction of the levodopa dosage by 40%, without deterioration of therapeutic response. In addition, feasibility of the overall approach based upon a sophisticated interplay between the practising neurologists (101) and the centers (27) was demonstrated. PMID- 1425820 TI - An interim report of the effect of selegiline (L-deprenyl) on the progression of disability in early Parkinson's disease. The Parkinson Study Group. AB - The pathogenesis of Parkinson's disease (PD) has been linked to oxidative mediated events including increased monoamine oxidase (MAO) and free-radical generation. We are investigating the ability of the MAO inhibitor, selegiline (deprenyl), and of the free-radical scavenger, tocopherol, to delay the onset of disability requiring levodopa therapy (primary end point) in patients with early PD. Eight hundred patients with early, untreated PD were enrolled in the multi center placebo-controlled, double-blind clinical trial 'Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP)'. Subjects were assigned by 2 x 2 factorial design to receive selegiline (10 mg/day), tocopherol (2,000 IU/day), a combination of both drugs, or placebo, and followed to determine if and when disability occurred requiring levodopa therapy. After 12 +/- 5 months of observation, independent monitoring prompted a preliminary analysis indicating that selegiline 10 mg/day significantly extended the time to the primary end point. Selegiline therapy, alone or in combination with tocopherol, resulted in a 57% reduction in the rate of developing disability requiring levodopa therapy (p < 10(-10)) and a 50% reduction in the rate of loss of full-time employment (p = 0.01). Deterioration of motor and mental features was significantly less in selegiline-treated subjects. Adverse effects were minor and infrequent. We conclude from these preliminary results that selegiline (10 mg/day) delays the onset of disability associated with early, otherwise untreated PD. It remains unclear whether these benefits derive from mechanisms that are symptomatic (dopaminergic), protective (anti-neurotoxic), or both. The DATATOP study is ongoing to examine the long-term effects of selegiline and the independent and interactive effects of tocopherol. PMID- 1425821 TI - Nation-wide collaborative study on the long-term effects of bromocriptine in the treatment of parkinsonian patients. Final report. AB - Final results of the 5-year multicentric collaborative study on the long-term effects of bromocriptine in the patients with Parkinson's disease are reported. This prospective study started in May 1985 in order to see whether the early combination therapy with bromocriptine and levodopa is really superior to the levodopa monotherapy with regard to the late side effects of levodopa in the treatment of parkinsonian patients. Another project of the study was to see the therapeutic efficacy of bromocriptine monotherapy without concomitant use of levodopa. For these purposes, a total of 702 patients with Parkinson's disease were enrolled into three groups: Group 1 (n = 286) with bromocriptine monotherapy, Group 2A (n = 216) with early combination of bromocriptine and levodopa, and Group 2B (n = 200) with levodopa alone. At the end of the 5-year study, 48 patients in Group 1 (16.8%) were still continuing bromocriptine monotherapy with satisfactorily good therapeutic effects. About half (49.1%) of the Group 2A patients remained on the combined therapy, and the comparable number of the Group 2B patients (46.0%) were also kept on the initial mode of therapy, while 13.5% of the latter group with levodopa monotherapy needed bromocriptine to be added in order to assure the good therapeutic effects. Moreover, significant differences were seen between group 2A and Group 2B with regard to the incidence of wearing-off phenomenon and dyskinesias. Disappearance rate of dyskinesias which were present at the time of enrollment was significantly higher in Group 2A than in Group 2B. No significant difference was noted as to the incidence of untoward symptoms and the death rate among all three therapeutic groups. These results support the view that the early combination of bromocriptine with levodopa is superior to levodopa alone in the treatment of Parkinson's disease. PMID- 1425822 TI - Sixty minutes normothermic ischemia in rat liver: the declining tissue concentration of hypoxanthine during reperfusion is not a washout phenomenon. AB - A rat liver normothermic ischemia-reperfusion model was used to investigate whether hypoxanthine (HXA) that accumulated during ischemia was washed out in hepatic veins during reperfusion. Ischemia was induced in median and left lobes by clamping of the proper hepatic artery and portal branches. The effect of allopurinol (ALL) on metabolism of ATP and HXA was studied before, during and after a 60-min normothermic ischemic insult. Liver cell concentration of HXA in the group treated with ALL increased during ischemia and decreased rapidly during the first 10-min reperfusion. Recovery of ATP increased gradually during the 10 min reperfusion period and was significantly higher in the group treated by ALL compared to that of controls. Liver venous blood concentration of HXA in the ALL treated group was 10-to 40-fold lower than that in liver tissue. The rapidly decreasing concentration of HXA in liver tissue during reperfusion and a minimal washout may indicate that HXA was used for resynthesis of ATP during reperfusion. PMID- 1425823 TI - Decrease in regeneration capacity of rat liver after external biliary drainage. AB - In order to discover the effect of external biliary drainage on liver regeneration, we have produced a model system carrying cannula in the common bile duct of rat liver and examined the regeneration capacity of liver after partial hepatectomy under various conditions. Previously we have shown that hepatic cells proliferate by obstructive jaundice alone without partial hepatectomy [Terasaki et al; Jpn J Cancer Res 1991;82:170-175]. In the present study, we showed that DNA polymerase-alpha was induced by partial hepatectomy of rats suffering from obstructive jaundice and the induced level was similar to that of the normal regenerating liver. The level of DNA polymerase-alpha activity corresponded well to the liver regeneration capacity estimated by mitotic index. Contrary to our expectation, external biliary drainage for obstructive jaundice markedly suppressed the regeneration capacity of the remaining liver which was estimated by DNA polymerase-alpha activity, mitotic index and [3H]thymidine incorporation. The suppression may be due to the external biliary drainage itself because the liver regeneration of normal rats without jaundice was also suppressed by the biliary drainage. These results suggest that the external biliary drainage seriously suppresses the regeneration capacity of liver at least at the early stage of obstructive jaundice. PMID- 1425824 TI - A standardized surgical technique to obtain a stable and reproducible chronic renal failure model in dogs. AB - The remnant kidney, a model of chronic renal failure in animals, can be obtained by two techniques: either surgical removal of tissue of one kidney, combined with contralateral nephrectomy or inducing necrosis of kidney tissue by ligation of branches of the renal artery of one kidney combined with contralateral nephrectomy. In the literature, most reports concern the ligation technique. The technique is safe and simple but the results in dogs are unpredictable. In this paper, both techniques were compared. We could demonstrate that the unpredictable result of the ligation technique is due to the formation of collateral vessels bypassing the ligated branches and to the inconstant ramification pattern of the renal artery. In this study, a standardized technique consisting of the resection of 16-18 g of tissue of one beagle kidney and removal of the other one is described. This method results in a stable chronic renal failure until the dogs are sacrificed at 9-12 months. PMID- 1425825 TI - Variations of magnesium, iron, copper and zinc during the colonic wound healing process: experimental study on rabbits. AB - The role of trace elements in the wound-healing process is still controversial. Their variations within a normal colonic wound healing have never been studied. An experimental study on rabbits was designed to study magnesium, iron, copper and zinc variations in blood, normal colonic walls and colonic anastomoses on each of the first 7 postoperative days. No major variations of Mg could be observed. Fe decreased in blood as well as in colonic walls and anastomoses. Cu increased in blood, whereas it decreased in colonic walls and anastomoses. Zn decreased in blood, whereas it increased in colonic walls without significant changes in anastomoses. The role of Fe seemed to be rather difficult to understand. Plasma mobilization seems to explain the local use of Zn, while early tissue release with further return in blood occurred for Cu. The importance of a well-balanced nutritional status is underlined to prevent and correct the variations of trace elements in the postoperative course. PMID- 1425826 TI - Whole pancreatic blood flow and islet blood flow in hypovolemic hypotension in rats. AB - The blood volume of adult, male rats was reduced with 5 ml (approximately 30% of the total blood volume) by bleeding, which reduced the mean arterial blood pressure (MAP) to 50 mm Hg. This hemorrhagic hypotension caused an increase in both serum glucose and serum insulin concentrations when compared with either normotensive control animals or with rats infused with nitroprusside to obtain an MAP similar to that of the bled animals. The blood perfusion of the whole pancreas was reduced in both groups of hypotensive animals but more markedly in those with hemorrhagic hypotension. The islet blood flow was reduced only in the bled animals. The percentage fraction of blood diverted through the islet organ was markedly increased in bled rats compared to the control animals, whilst this increase was less pronounced in the nitroprusside-infused rats. The vascular conductance in the nitroprusside-treated rats was unchanged for the whole gland, but increased for the islets. Both these values in bled animals were decreased. It is concluded that the blood flow regulation differs between the endocrine and exocrine parts of the pancreas in hypovolemic hypotension. PMID- 1425827 TI - Effect of activated protein C on impaired fibrinolysis in rats with obstructive jaundice. AB - We studied the effect of activated protein C (APC) on impaired fibrinolysis using a rat model in which disseminated intravascular coagulation (DIC) is induced by the intravenous injection of endotoxin in rats with obstructive jaundice. An intravenous injection of endotoxin in rats with obstructive jaundice resulted in pulmonary hemorrhages and a marked increase in the plasma levels of tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor activity. Prophylaxis with APC before the injection of endotoxin resulted in a decrease of the number of lung hemorrhages and an accelerated release of t-PA antigen. Thus, DIC in obstructive jaundice may be due to impairment of fibrinolysis and an increased susceptibility of endothelial cells to endotoxin. APC may be effective as a treatment for patients with obstructive jaundice associated with DIC. PMID- 1425828 TI - An electrohydrothermosation system for application in endolaryngeal and enoral surgery: a technical report. AB - The use of medical lasers or high-frequency (HF) devices ('electrocautery') allows the dissection of tissue by an application of heat. The main advantage of such techniques is the reduction of intra-operative bleeding. On the other hand, carbonization and coagulation lead to difficulties in the histological investigation of the resected specimen. Electrohydrothermosation (EHT) systems are irrigation-supported HF devices. The cutting or coagulation electrodes are continuously rinsed with distilled water in order to minimize thermal interactions with the tissue. We developed an EHT system for endoscopic head and neck surgery. The system was used to remove defined specimens from pig larynges and tongues experimentally. We compared the results with those obtained by a surgical CO2 laser and found that carbonization and overall tissue damage were less severe with EHT than with laser surgery. This leads to the conclusion that EHT is an improvement of conventional HF surgery and may be an alternative to laser surgery in the head and neck. PMID- 1425829 TI - The role of the gastrointestinal microflora in postsurgical adhesion formation--a study in germfree rats. AB - The elucidation of the pathogenesis of postsurgical adhesion formation is still lacking. In this study experimental adhesion formation was studied in germfree (i.e. void of bacteria) and conventional rats (intestinal flora comprising over 400 species) using a caecal crush model. The germfree rats responded significantly weaker to the same stimuli, forming adhesions in only 20% of the cases as compared to the conventional rats 87.5% (p = 0.0076). The findings indicate that the bowel flora is of importance but not essential for postsurgical adhesion formation in rats. PMID- 1425830 TI - Tumor collagenase-stimulating factor and tumor autocrine motility factor as tumor markers in bladder cancer--an update. AB - We have studied the role of combined measurements of tumor collagenase stimulating factor (TCSF) and tumor autocrine motility factor (TAMF) in 83 first morning voids and 24-hour specimens in patients with bladder and renal cancer and control subjects. TCSF and TAMF were measured by immunoabsorption assay and motility test utilizing modified Boyden chamber. The mean concentrations of urinary TCSF and TAMF from cancer patients (n = 32) were 4- to 5-fold higher than those from benign conditions (n = 70). We compared TCSF and TAMF utilizing motility test in first morning voids (n = 18) and 24-hour urinary samples (n = 19). TCSF and TAMF were almost identical in terms of eluted proteins from morning voids and 24-hour urine samples. Invasive bladder cancer (n = 12) showed a significantly higher correlation (r = 0.9 and p = 0.0001) between motility response and urinary concentration of TCSF and TAMF. We have also localized these two glycoproteins in cell membranes and cytoplasms of cancer cell. PMID- 1425831 TI - Tissue polypeptide antigen for monitoring of advanced bladder cancer after MVEC chemotherapy. AB - 58 patients with advanced bladder cancer were treated with MVEC chemotherapy (methotrexate, vinblastine, epirubicin and cisplatinum). 22 patients suffered from locally advanced disease (pT3-4 M0 N0), in 20 patients regional lymph node metastases were found (pT3-4 N1-3 M0). In 16 patients distant metastases were noted (pT1-4 N0-1 M1). In 89% transitional cell and in 11% squamous cell cancer or anaplastic carcinoma was seen. Complete response was noted in 45%, partial response in 23% and no response in 32%. Tissue polypeptide antigen (TPA) was registered before each course of chemotherapy and 3 months after the last application. The sensitivity for (pT3-4 N0 M0) tumors was 90.9%, for (pT3-4 N1-3 M0) 100% and for tumors with distant metastases 100% also, overall 96.6%. No statistically significant different values between each tumor group were found. In 85.7% a concordant reaction of TPA values and clinical status was notable. In conclusion, TPA has been proven as a valuable and a reliable marker for monitoring therapeutic efficacy of chemotherapy for advanced bladder cancer. PMID- 1425832 TI - Bladder wash cytology and flow cytometry for the diagnosis of transitional cell carcinoma of the urinary bladder. AB - The role of bladder wash (BW) cytology and flow cytometry in the diagnosis of low grade transitional cell carcinoma (TCC) of the bladder is yet to be demonstrated. We have studied a series of BW specimens by both conventional cytology and flow cytometry: there were 16 BW from patients with histologically proven TCC and 14 BW from patients with clinical suspicion of tumor or under follow-up for previous TCC in which no evidence of tumor was found by cystoscopy and multiple biopsies. As control group, 21 BW were studied from patients undergoing cystoscopy for causes other than TCC. In conclusion, the conventional cytologic study of BW specimens was highly sensitive for grade II-III TCC, but missed most grade I TCC; flow cytometric analysis did not improve significantly the detection rate in low grade TCC. PMID- 1425833 TI - Prognostic role of flow cytometry in superficial bladder cancer. AB - Prognostic factors in superficial transitional cell carcinoma of the bladder were assessed with histopathological and flow cytometry analysis in a series of 61 patients operated transurethrally between 1988 and 1990. In particular, we evaluated the usefulness of flow cytometry in order to identify patients who require a more accurate clinical follow-up or a more aggressive therapy. A multivariate analysis was done in 61 cases, considering patient age and sex, stage, grade and number of lesions (unifocal or multifocal), post-TUR therapy (therapy or not), and DNA ploidy (diploid/aneuploid). DNA pattern and number of recurrences were determinant for selecting risk cases for progression. PMID- 1425834 TI - Prediction of recurrence and progression in primary superficial bladder cancer with DNA flow cytometry. AB - Intravesical chemotherapy has been well established as an effective therapy for recurrent superficial bladder tumors. We investigated the role of flow cytometry as a predictor of tumor recurrence/progression after intravesical chemotherapy. Flow cytometric analysis of nuclear DNA ploidy pattern was performed on 'cold cup' biopsy samples of 52 patients with primary superficial bladder cancer. Cell suspensions, retrieved after mechanical fragmentation, were stained with propidium iodide and examined on FACScan flow cytometer. Clinical follow-up ranged from 3 to 57 months with a median of 20 months. Of the 52 patients, 24 aneuploid and 28 diploid tumors were observed. The degree of ploidy in relation to histological grade showed an increasing frequency of aneuploid pattern in grades 2 and 3 but with no statistical significance. 17.8% of diploid tumors versus 54.1% of aneuploid tumors recurred (p less than 0.05). 12.5% of the aneuploid tumors progressed. No progression among diploid tumors was observed. Of the 52 patients examined, 35 (16 aneuploid and 19 diploid) were treated, after TUR, with intravesical prophylactic therapy. Epirubicin in 24, mitomycin C in 4 and recombinant interferon alpha 2a in 7 were used. 50% of aneuploid tumors versus 10.5% of diploid tumors recurred (p less than 0.05). Strong predictors of response to intravesical prophylaxis of recurrence were G1 grade and diploid DNA content. PMID- 1425836 TI - The prognostic significance of DNA ploidy pattern in transitional cell cancer of the renal pelvis and ureter: continuing follow-up. AB - Among 190 patients operated on for transitional cell cancer of the renal pelvis and/or ureter from 1976 to 1990, 95 had their tumor studied by flow cytometry. Of these, the prognostic significance of the DNA ploidy pattern with respect to the standard pathologic features was assessed in a retrospective analysis, where survival information were updated to October 1991 and the mean follow-up of patients exceeded 5.5 years (longest follow-up: 15.5 years). Five and ten-year survival probabilities for the whole group were, respectively, 65.5 and 51%. Patients with a diploid tumor had significantly better survival rates than patients with tetraploid/aneuploid cancer (p less than 0.00001). The impact of the DNA ploidy on survival was confirmed by a multivariate analysis of prognostic factors, where only tumor grade (p less than 0.0001), tumor stage (p less than 0.0001), number of neoplastic foci (p = 0.022) and nuclear DNA pattern (p less than 0.068) had a significant influence on survival. In the group of patients with low-stage (pTa-pT1) and low-grade (G1-G2) transitional cell cancer of the upper urinary tract, the DNA analysis was unable to identify any subset of patients at higher risk for disease progression. PMID- 1425835 TI - Biological and clinical implication of cellular DNA content in renal cell carcinomas. AB - DNA flow cytometric analysis (FCM) was performed on surgical bioptic samples taken from 82 renal cell carcinomas. FCM has evidenced that 35% (29/82) of renal carcinomas resulted diploid, 65% (53/82) aneuploid and of the latter 22% (12/53) multiclonal. Our results do not indicate any relationship among cytometric ploidy, Fuhrman grading, Robson and pTNM staging. A possible interesting increase of aneuploidy frequency was observed between the NMV (66%) subgroup and the no zero NMV (90%) subgroup, while in diploid patients these values were 40% and 10%, respectively. Follow-up data evidence a significant difference in survival pattern of patients between diploid and aneuploid groups. In conclusion, our results show that cytometric ploidy is a potential important prognostic parameter in survival term. PMID- 1425837 TI - Morphometric and immunohistochemical characterization of bladder carcinoma in situ and its preneoplastic lesions. AB - We performed a morphometric and immunohistochemical study of 26 bladder carcinoma in situ (Cis) specimens, compared with normal urothelium and urothelial preneoplastic lesions. The following morphometric parameters were evaluated: nuclear area, nuclear perimeter and maximum nuclear diameter. For the immunohistochemical study we used five lectins, antibodies against four epithelial differentiation antigens, and antibodies against blood group isoantigens. A progressive increase in nuclear size from normal urothelium to dysplastic urothelium and Cis was detected. Nuclear size values in Cis and in high-grade, high-stage bladder carcinomas were similar. The most relevant immunohistochemical results were obtained with CEA, CK, UEA-1 and ABH isoantigens, which show significant immunoreactivity changes in preneoplastic urothelium and Cis when compared with normal urothelium. We conclude that bladder Cis behaves morphometrically and immunohistochemically as an invasive bladder carcinoma, and we emphasize the usefulness of these techniques for detecting flat dysplastic and neoplastic lesions in random bladder biopsies. PMID- 1425838 TI - Erythrocyte sedimentation rates in patients with renal cell carcinoma. AB - The importance of erythrocyte sedimentation rate (ESR) in patients with renal cell carcinomas (RCCa) is still controversial. ESR levels increased in over half of these patients. In this study, ESR levels of 19 patients with RCCa were investigated (85.368 +/- 5.914). In 11 patients in whom carcinomas were only localized in the kidney, the ESR levels were detected as 78.182 +/- 8.686. In 8 patients who had metastasis, the ESR levels were found as 95.250 +/- 6.427. ESR levels were also estimated in 15 healthy adult persons as control group (18.133 +/- 2.180). Mean ESR values were significantly higher in the tumor group than in the control group (p less than 0.01). There was no statistical difference of the ESR levels between the patients who had local RCCa and advanced RCCa (p greater than 0.05, NS). The removal of the tumoral mass caused the ESR levels to diminish. In conclusion, the ESR levels were not a good criteria in patients with RCCa for evaluating either prognosis or metastasis. PMID- 1425839 TI - DNA markers in diagnosis of adult dominant polycystic kidney disease. AB - We report the results of a biological and molecular study carried out on 11 Italian families, with a total of 111 individuals in which adult dominant polycystic kidney disease segregates. A restriction fragment length polymorphism analysis was performed. Two families have shown a genetic heterogeneity even if not phenotypically different from the other ones: they resulted unlinked to 16p markers. A prenatal diagnosis has been performed in a family of the linked type. PMID- 1425840 TI - Identification of new prostate cancer progression markers by differential hybridization analysis. AB - In studies on the onset and progression of cancer, molecular biology has proven to be very useful. Reasoning that tumorigenesis can be considered as a multistep process in which a normal cell gradually escapes from its delicately regulated growth pattern, one might describe this process in terms of gene expression. The group of genes that are good candidates for such studies are the proto-oncogenes. Recent progress in oncogene research, however, has made us believe that the group of oncogenes is much greater than the 50 so far characterized, since all growth factor-, growth factor receptor-, signal transducer- and transcription-regulating genes have a potency to become oncogenic. Alternatively, recessive genes, such as tumor suppressor genes, might be equally relevant to the onset and progression of cancer. Therefore, new approaches in molecular studies on the genesis and progression of malignancies are urgently needed. One of these methods is the so called differential or subtraction hybridization analysis. Particularly, the rationale of differential hybridization and the first applications to prostate cancer research are discussed in this paper. PMID- 1425841 TI - Nucleolar organizer regions: preliminary results of the clinical use of a new marker for prostatic carcinoma (40 cases). AB - It is a widely diffused opinion that moving backwards in time the moment of the diagnosis of cancer of prostate, so that the tumor is detected earlier than normal, means that the treatment would be more effective than the one adopted in the usual times of diagnosis. For this reason the earlier diagnosis of prostate cancer has become more and more a compulsory target of the modern urologist, at a time of booming of the third age, of increased lifetime expectancy, of significant elevation of prostate cancer rate and of the persistent uncertainty of the efficacy of available treatments. Theoretically the mortality rate of prostate cancer can be reduced by the prevention programs and by the improvements of treatment methods, but the 'earlier' diagnosis is certainly an easier and less expensive strategy to achieve the same objective. The authors have evaluated the argyrophilic-nucleolar organizer region (Ag-NOR) proteins on 40 cases of adenocarcinoma of prostate collected through a multicentric program in France and in Italy. The Ag-NOR have been stained with silver technique set up by Ploton and Derenzini while the quantitative index has been evaluated by a semiautomatic system partially commercially available, partially modified by the authors. The conclusions: (a) the Ag-NOR index is a simple and reproducible method; (b) the Ag NOR staging system corresponds to Gleason's grading; (c) the Ag-NOR elevation is a reliable marker of increased cell proliferation and is detectable much earlier than the morphologic changes of Gleason's classification. PMID- 1425842 TI - The prognostic value of DNA content in patients with prostatic carcinoma. AB - In 80 patients with pathologically proven prostatic cancer, DNA content was correlated to grade, stage and survival. The survival curve and duration of response to therapy in these patients was examined. At the end of follow-up the cumulative survival curve in the aneuploid patients was 0.40, according to the Kaplan-Meier method, while in the diploid population it was 0.65. Differences between the two groups, aneuploid and diploid, were observed within the various histological subgroups: survival in the G2 population was 0.57 for the diploid and 0.30 for the aneuploid whereas in the G3 patients it was respectively 0.69 for the diploid and 0.05 for the aneuploid patients. PMID- 1425843 TI - Reappraisal of radical perineal prostatectomy. AB - Radical prostatectomy is frequently the treatment of choice for localized adenocarcinoma of the prostate. The procedure can be accomplished through either a perineal or a retropubic approach; both have their advantages and disadvantages. Recently, concerns over transmission of blood-borne viruses during transfusions and the advent of laparoscopic pelvic lymphadenectomy have resulted in a rejuvenation of interest in perineal prostatectomy. Herein, we discuss the history of perineal prostatectomy, the technique and its advantages and disadvantages. PMID- 1425844 TI - Results of a questionnaire among Dutch urologists and general practitioners concerning diagnostics and treatment of patients with prostatitis syndromes. AB - By means of a questionnaire, all Dutch urologists (n = 250, 136 responded) and regional general practitioners (GPs; n = 400, 176 responded) were contacted concerning current diagnostics and treatment modalities applied in patients with prostatitis syndromes. The patients seen by urologists seem to be younger (30-40 years) and they mostly complain of pain in the perineum, penis or scrotum, while GPs see older patients (> 40 years) mainly presenting with micturition complaints. Urologists think nonbacterial causes (40%) most important, while GPs mention bacterial infections (63%) as the most important cause. The first choice of therapy is antibiotics, mostly co-trimoxazole Sulfatrim for 3 weeks, but patients seen by urologists are more resistant to this therapy. If not successful, urologists frequently prescribe a second course with antibiotics. However, many urologists think psychosomatic causes are an important factor in the etiology of prostatitis. PMID- 1425845 TI - Surgical repair versus medical treatment of varicocele in the rat: pharmacological manipulation of the varicocelized testicle. AB - Human chorionic gonadotropin, kallikrein, indomethacin, and hydralazine were administered to different groups of varicocelized rats, while surgical repair of the varicocele was performed in another group of rats. The effects of conservative and surgical treatment on epididymal sperm content and motility, the weights of the testes, epididymis, and male accessory genital glands, and fertility were compared between each group and a sham-treated group of rats. Surgical repair significantly improved all the evaluated parameters and all the conservative regimens, except hydralazine, resulted in a significant improvement in most parameters. Our results indicate that stimulation of the Leydig or/and Sertoli cells of a varicocelized testicle can counteract some of the detrimental consequences of the varicocele itself. PMID- 1425846 TI - Epididymitis in children and adolescents on clean intermittent catheterisation. AB - The records of 119 children and adolescents on clean intermittent catheterisation (CIC) were reviewed to assess the incidence and predisposing factors, if any, of epididymo-orchitis. CIC had been performed for a total of 448 patient years with a mean of 4.5 years (range 3 months to 19 years). Of the evaluable 99 patients, 10 suffered attacks of epididymo-orchitis after commencing CIC. There was an equal incidence on both sides. Three patients had recurrent attacks. Epididymitis occurred at the rate of 1 episode for 10 patient years. Those who had neuropathic bladders and more than 2 symptomatic urinary tract infections annually had a higher incidence. Prophylactic antibiotics did not reduce the incidence but long term specific antibiotic therapy may prevent further attacks. Vasectomy and orchidectomy had to be done in 2 patients for recurrent attacks and intractable sepsis. PMID- 1425847 TI - Modified meatal advancement and glanduloplasty with complete foreskin reconstruction. AB - We report 28 boys who underwent repair of a distal hypospadias with a combination of a modified meatal advancement and glanduloplasty and reconstruction of the foreskin. An excellent result was achieved in 24 patients. In 4 boys, preputial reconstruction failed. Only one group of parents demanded further surgery. Improved cosmetic results with avoidance of serious complications make this operation ideal for treating distal hypospadias in countries where the circumcised penis is an exception. PMID- 1425849 TI - Effect of high-energy shock wave frequency on viability of malignant cell lines in vitro. AB - In this study, the effects of high-energy shock wave (HESW) frequency on the viability of three different malignant cell lines were evaluated using a piezo electric generator. The cell lines studied were AR42-J, VX-2 and HeLa. These cells were targeted both in free suspension and immobilised in gelatine beads. All cell lines in free suspension were acutely sensitive to HESW over a range of frequencies. When cells were immobilised in gelatine, however, the effect on cell viability was not as pronounced. However, at frequencies of 80- and 160-Hz kill rates approaching 80 and 90%, respectively, were observed. Cell proliferation following HESW treatment was not adversely affected. This study demonstrates that single cell suspensions are not appropriate for assessing the in vitro cellular effects of HESW. However, even when cells were immobilised in gelatine, high frequency HESW produced substantial kill rates. The effects of high-frequency HESW merit further evaluation particularly using in vivo tumour. PMID- 1425848 TI - In vitro lithotripsy with the Alexandrite laser. AB - The Alexandrite laser system has proven to be an effective and safe method of ureteral lithotripsy. Some authors have recently reported the risk of interspersion of fiber splinters into tissue during lithotripsy, when short pulses and high power densities are employed. In vitro lithotripsy on renal calculi artificially placed in human ureters was realized under the parameters of a manufactured model (Alexantriptor, HMT). We have observed neither interspersion of fragments nor ureteral damage. These in vitro experiments and our clinical experience confirm that Alexandrite laser lithotripsy is reliable and safe. PMID- 1425850 TI - Experimental model for ureteral autotransplantation in the rat. AB - The development of an experimental model for ureteral autotransplantation without kidney transplantation, in an attempt to confirm viability of the ureter after denervation and total ischemia, is reported. Stages of the study and the experimental microsurgical technique used are discussed. Experiments were carried out in 30 Sprague-Dawley rats distributed in two experimental stages. The absence of histologic lesions was demonstrated by exeresis of the autotransplantated ureter and latter pathological study. Size, colour, renal consistency, ureteral peristalsis and the macroscopic appearance of the surgical piece were recorded. Histological examination confirmed macro- and microscopic normality of the autotransplanted ureteral segment. PMID- 1425851 TI - Implantation metastasis after a suprapubic catheter in a case of bladder cancer. AB - We report about a patient who was treated with a percutaneous suprapubic cystostomy in order to relieve repeated urinary retention. Two hours later a bladder tumor was found and the suprapubic catheter was removed. After transurethral resection of the bladder tumor the histological specimen showed a pT3 G3 squamous cell carcinoma. Because of the age and reduced performance status of the patient a radical cystectomy was contraindicated. In a second approach we performed again a transurethral resection of the bladder tumor simultaneously with a resection of the prostate. Eight weeks later the patient was admitted to our hospital because of reduced performance status and gross haematuria. We found a widespread bladder tumor with an implantation metastasis in the abdominal wall at the site where the suprapubic catheter was placed and multiple lung metastases. The patient died within one week after admission. The literature is reviewed and therapeutic strategies are discussed. PMID- 1425852 TI - Embracing new special education strategies for African-American students. PMID- 1425853 TI - Culturally sensitive instructional practices for African-American learners with disabilities. AB - This article discusses the cultural and educational needs of African-American learners with disabilities. Six theoretical assumptions establish some basic suppositions about culturally and linguistically diverse learners and effective instructional practices. A review of the literature describes African-American cultural practices, interests, and cognitive styles; highlights the attitudes, perceptions, and instructional practices of effective teachers of African American students; and includes patterns of teacher-student and peer-group interactions that promote high academic achievement among African-American learners. Recommendations include organizing teaching, learning, and performance in ways that are compatible with the social structure of African-American students with disabilities. PMID- 1425855 TI - Early pregnancy and academic achievement of African-American youth. AB - Competing demands of school and home can thrust adolescent mothers into stressful situations. Meeting the requirements to achieve academically can be a challenge, especially for students previously identified as "slow learners." These students may conclude that academic achievement is an impossibility. How can special educators and service providers help? What environmental variables affect these young mothers' learning capabilities? This study used a case study research approach to study 10 African-American adolescent mothers who were already at risk of dropping out of school programs. Successful strategies to keep these students in school include school-based clinics, teacher training, sex education, and school-community support. PMID- 1425854 TI - The use of selected theatre rehearsal technique activities with African-American adolescents labeled "behavior disordered". AB - The extensive literature on the overrepresentation of adolescent African-American male learners in classes for students identified as behavior disordered has essentially not addressed the problems caused by teacher reactions to adolescent conversational language use, the qualitative differences in language choices, or the impact of the conversational choices of adolescents on their educational treatment. This article explores how the dramaturgical perspective of selected Theatre Rehearsal Technique (TRT) activities can be used as learning experiences in communication with this student population. If these students gain quantifiable success in their social communication interactions, reassessment of their special education placement might facilitate their entrance into less restrictive educational environments. PMID- 1425856 TI - The pitfalls and promises of special education practice. AB - It is imperative that special education enable children with disabilities to achieve at high levels. Problems of equity and pedagogical validity have hindered our efforts thus far, and many children of minority cultures are far overrepresented in classrooms for students with learning disabilities and mild mental retardation. Studies have shown the importance of culturally and linguistically inclusive programs and of heterogenous groupings, as well as more effective diagnostic, remedial, and assessment practices. This article discussed a model and basic principles for such techniques to ensure that the educational outcomes of all children are improved. PMID- 1425857 TI - Determinants of coronary effects of atrial natriuretic factor in dogs. AB - The direct vascular action of atrial natriuretic factor (ANF) is unclear. In coronary vasculature, vasodilation has been reported as well as vasoconstriction. Doses of ANF, baseline plasma ANF levels and interference with the renin angiotensin system might account for the controversy. We tried to further analyse determinants of the effect of ANF on coronary blood flow in anaesthetized dogs. The chest was opened and the left anterior descending coronary artery cannulated and perfused at constant normal (= 76 +/- 5 mmHg, n = 10) or reduced (= 37 +/- 3 mmHg, n = 10) pressure from the femoral arteries. At normal coronary perfusion pressure, ANF (1 ng kg-1 i.c.) reduced coronary flow from 30.7 +/- 4.2 to 26.9 +/ 4.0 ml min-1 (P less than 0.05). This effect was no longer significant at reduced coronary perfusion pressure (4.9 +/- 0.8 vs. 4.6 +/- 0.7 ml min-1). ANF (1 ng kg-1 i.c.) reduced coronary blood flow in correlation with baseline plasma ANF levels (r = 0.77, P less than 0.001). However the large variability of the constrictor effect of ANF in the rather small range of baseline plasma ANF, weakens the importance of this result and suggests other additional determinants. ANF (100 ng kg-1 i.c.) significantly increased coronary blood flow by 16-23% (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425858 TI - Reappraisal of the role of insulin on sodium handling by the kidney: f1fect of intrarenal insulin infusion in the dog. AB - Since several studies suggest that increased insulin levels may induce antinatriuresis, the present work was undertaken to determine whether a physiological increase in insulin levels in blood perfusing the kidney may exert direct effect on kidney function, and more specifically on sodium reabsorption. To this end, insulin was infused directly into one renal artery of 10 anaesthetized dogs at the rate of 4 mU min-1 for a period of 90 min. The contralateral kidney was infused with saline alone, to provide reference values. Insulin level in the renal vein of the insulin-infused kidney went up from 1.4 +/ 0.9 before to 30.6 +/- 7.1 microU ml-1 after 90 min of insulin perfusion. There was no significant effect on renal plasma flow, glomerular filtration rate and renal uptake of substrates or oxygen between ipsi- and contralateral kidney. The fractional excretion of sodium was likewise unaffected, since it averaged at the end of insulin infusion 0.41 +/- 0.11% vs. 0.50 +/- 0.14% for the contralateral saline infused kidney. Even if one may assume that the baseline low insulin concentrations promote tubular sodium reabsorption, the results of the present study suggest that a moderate hyperinsulinaemia is without any additional effect on renal sodium handling. PMID- 1425860 TI - Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis. AB - With advancing age both sexes have an increased incidence of osteoporotic fractures, although fractures are more common in women than in men. Whereas in women several potential risk factors have been identified, less is known about osteoporosis in men. A total of 27 Austrian men (mean age: 65 +/- 2 years) with atraumatic spine fractures were studied. In all patients, medical history gave no evidence of disease or medications causing osteoporosis. Peripheral bone mass was determined by single-photonabsorptiometry on the distal non-dominant forearm; lumbal bone density was measured by quantitative computed tomography. Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, testosterone, estrogen, parathyroid hormone and 25-hydroxy-vitamin D as well as 2-h-urinary-OH proline and calcium excretion were measured. All data were compared with those of an age and sex matched control group consisting of 19 healthy males. A significant difference in mean peripheral and axial bone mass (SPA: P less than 0.004; QCT: P less than 0.0001) was observed between osteoporotic men and controls. When compared to controls, serum levels of alkaline phosphatase (P less than 0.012), urinary OH proline (P less than 0.05) and urinary calcium excretion (P less than 0.003) were significantly higher in the osteoporotic males. Additionally, there was a significant positive correlation between serum alkaline phosphatase and urinary OH proline excretion (r = 0.32; P less than 0.04) in the osteoporotics. All other biochemical parameters showed no significant differences. Our results may lead to the assumption that osteopenia in men is related to increased bone turnover. PMID- 1425859 TI - Normal lipoprotein(a) concentrations and apolipoprotein(a) isoforms in patients with insulin-dependent diabetes mellitus. AB - Lipoprotein(a) [Lp(a)] is an LDL particle in which apoliporotein B-100 is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated, and plasma Lp(a) concentrations above 20-30 mg dl-1 are an independant risk factor for ischaemic heart disease (IHD). To investigate whether Lp(a) could be important for the high cardiovascular mortality rate in patients with insulin dependent diabetes mellitus (IDDM), we determined Lp(a) concentrations and phenotypes in a group of 108 men (median age 32 years) with IDDM without nephropathy. A group of 40-year-old men (n = 466) served as controls. The median Lp(a) concentration was 7.4 mg dl-1 [95% CI 4.9 to 11.7] in the diabetic patients and 6.3 mg dl-1 [95% CI 5.2 to 7.0] in controls. The Lp(a) concentration exceeded 30 mg dl-1 in 22% of IDDM patients and in 20% of controls (P = 0.13). Moreover, the distribution of apo(a) phenotypes did not differ between patients and control. Lp(a) levels and apo(a) phenotypes are thus apparently the same in IDDM patients without nephropathy and controls. These findings do not exclude the possibility that Lp(a) may be increased in patients with nephropathy in whom coronary artery disease frequently co-exist or that Lp(a) in a given concentration is more atherogenic in IDDM patients than in persons without IDDM. PMID- 1425861 TI - Nutritional behaviour and quality of life during oncological polychemotherapy: results of a prospective study on the efficacy of oral nutrition therapy in patients with acute leukaemia. AB - A total of 29 patients with acute leukaemia were prospectively randomized before starting cytostatic treatment to be nourished either with intensified oral nutrition (intervention group) or ad libitum nutritional intake during the whole tumour therapy (median 22 weeks). All received menus of free choice (daily offer of 1.0-2.0 g protein, 30-50 kcal kg-1 body weight (BW)). Beyond this, intervention patients received nutrition education, daily visits by the dietician and record of food intake, as well as a weekly assessment of subjective well being (linear analogue self assessment 'LASA'). From the LASA items, the factors: 'malaise', 'psychological distress', 'therapy side-effects' were extracted by principal component analysis, and correlated to nutrient intake and nutritional status. At the end of antineoplastic induction therapy, after continuous hospitalization of 10 weeks (median), 31.3% of the controls had regained their initial nutritional status, and 68.8% of the intervention group. Mean daily energy intake was 23.2 kcal kg-1 BW during weeks with weight loss (constant weight: 30.9, weight gain: 39.3 kcal kg-1 BW). Nutritional behaviour correlated with subjective well-being, low intake with complaints of tumour treatment side effects and weight loss with malaise. PMID- 1425862 TI - A comparison of octreotide delivered by continuous subcutaneous infusion with intermittent injection in the treatment of acromegaly. AB - This study was undertaken to evaluate GH, IGF1 and drug levels during incremental continuous subcutaneous infusion of octreotide and compare these parameters following long-term treatment of 300 micrograms 24 h-1 by intermittent injection in a group of acromegalic patients. Ten patients were treated by continuous subcutaneous infusion in increasing dose from 200 micrograms 24 h-1 to 1600 micrograms 24 h-1; this resulted in consistent 24-h growth hormone suppression (less than 5.0 mU l-1), and normalisation of IGF1; the optimum dose was 400 micrograms 24 h-1, the maximum dose was tolerated without any untoward effects. There was no deterioration in carbohydrate tolerance despite a marked decrease in fasting and stimulated insulin levels. After 1 year of maintenance treatment, 300 micrograms 24 h-1 by intermittent injection, patients were re-evaluated; GH levels were not so consistently suppressed over the 24-h period and carbohydrate tolerance had deteriorated. A sub-group of patients with sub-optimal GH suppression on this regimen were identified and reassessed after 6 weeks treatment with an increased dose, 600 micrograms 24 h-1 by intermittent injection; both mean GH suppression and carbohydrate tolerance improved. The dose of drug and method of administration is best adjusted for each patient to achieve optimum GH suppression, thereby minimise compensatory hyperinsuliaemia and hopefully reduce morbidity and mortality. Alterations in pituitary tumour size and acquisition of gallstones during treatment have been observed which substantiate the need to re-evaluate these parameters on routine follow-up of acromegalic patients on long-term octreotide. PMID- 1425863 TI - Renal reserve filtration capacity in growth hormone deficient subjects. AB - In normal subjects, the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) acutely increase in response to infusion of amino acids and to low doses of dopamine. It is uncertain whether circulatory growth hormone (GH) is a permissive factor for these stimulatory effects. GFR and ERPF (constant infusion technique using 125I-iothalamate and 131I-hippuran, respectively) were measured before and during the infusion of dopamine and amino acids in 8 GH deficient subjects. The clearance study was repeated during concomitant administration of octreotide to investigate whether this somatostatin analogue would modify the amino acid and dopamine-induced renal haemodynamic changes. Dopamine increased baseline GFR from 89 +/- 3 (mean +/- SEM, n = 8) to 102 +/- 4 ml min-1 1.73 m-2 and ERPF from 352 +/- 19 to 476 +/- 26 ml min-1 1.73 m-2, P less than 0.001 for both. During amino acid infusion GFR and ERPF increased to 108 +/- 3 and 415 +/- 23 ml min-1 1.73 m-2, respectively, P less than 0.001 for both. Octreotide did not significantly decrease baseline and dopamine-stimulated renal haemodynamics but lowered the amino acid-stimulated GFR (98 +/- 4 ml min-1 1.73 m-2, P less than 0.05) and ERPF (381 +/- 18 ml min-1 1.73 m-2, P less than 0.05). Basal plasma glucagon concentrations were not suppressed by octreotide, whereas the amino acid-induced increments in plasma glucagon were partially inhibited. It is concluded that GH is not a necessary factor for the stimulatory effects of amino acids and dopamine on renal haemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425864 TI - Doctors' perception of pertinent information. Results of a survey of a random sample of French general practitioners. GEP (Groupe d'Etude de la Prescription). AB - The results of a survey aimed at investigating which tools prescribers have at hand to help them to identify pertinent information from a background of "noise" are reported. A questionnaire was sent to 250 general practitioners randomly selected from a list of those practicing in the Rhone-Alpes region in France, of whom 117 (46.8%) replied. The questionnaire consisted of three sections, the first explored how they dealt with intermediate and clinical outcomes in trials, the second presented a series of statements to identify what would make them prescribe a new drug, and the third looked at their knowledge of therapy assessment methodology. It was found that most general practitioners had not been trained to identify the most salient information for selecting the best treatment. This implies that both medical students and qualified doctors should be taught to recognise pertinent information. PMID- 1425865 TI - Dose ranging study of lansoprazole, a new proton pump inhibitor, in patients with high gastric acid secretion. AB - The effects of single doses and of 7 days of lansoprazole 10, 20 and 30 mg PO versus placebo on gastric acid secretion have been evaluated in 8 patients with high gastric acid secretion. The double blind crossover period was followed by a simple blind 7 days on placebo to detect any rebound phenomenon. After the first dose lansoprazole did not modify basal acid output (BAO) but it significantly and dose dependently inhibited peak acid output (PAO) and increased the time during which nocturnal intragastric pH was greater than 3. After 7 days of treatment the same significant, dose-dependent suppression of gastric acid was found, but BAO was also blocked. One week after cessation of lansoprazole administration no rebound increase in gastric acid-secretion was observed. The plasma gastrin concentration remained unchanged throughout the study. PMID- 1425866 TI - Simultaneous noninvasive evaluation of gastric emptying and orocaecal transit times. Use in studying the actions of cisapride in diabetic patients. AB - The aim of the study was to use a novel combination of two methods for the simultaneous evaluation of two effects of oral cisapride in 10 diabetic patients with autonomic neuropathy; gastric empyting time was measured by following radio opaque markers and orocaecal transit time by the sulphasalazine-sulphapridine method. The study was of double-blind, randomized, placebo-controlled, cross-over design. It was possible to evaluate the effect of a prokinetic drug on gastric emptying and orocaecal transit times using these two noninvasive techniques at the same time. Cisapride significantly reduced both the gastric empyting (1.2 h versus 2.1 h) and orocaecal tansit (5.9 h versus 7.7 h) times. PMID- 1425867 TI - Nocturnal oxygen saturation and sleep quality in patients with advanced chronic obstructive pulmonary disease during treatment with moderate dose CR theophylline. AB - The effect of a 24-h controlled-release (CR) preparation of theophylline (Th) on nocturnal arterial oxygen saturation (SaO2) and sleep quality has been evaluated in 7 patients with advanced chronic obstructive pulmonary disease (COPD) in a double-blind cross-over experiment; median values: age 61 y; PaO2 8.0 kPa; PaCO2 5.8 kPa. During treatment with 450-900 mg Th in the evening, morning plasma drug levels ranged from 5.2-12.9 micrograms.ml-1. During Th and placebo treatment, the median evening FEV1 was 0.45 l and 0.46 l, respectively, and the morning FEV1 was 0.53 l and 0.41 l. Sleep was monitored by whole-night polysomnographic recording of oximetric SaO2, airflow, respiratory and body movements (static charge sensitive bed), eye movements and submental electromyogram. There was no significant difference between Th and placebo in sleep quality. Th treatment was associated with a marginal improvement in nocturnal oxygenation in most of the patients; the average nocturnal SaO2 ranged from 84.4%-92.8% during Th and from 82.2-90.5% during placebo treatment, respectively. Only in the morning, during the last 2 h in bed, was the slight difference in SaO2 statistically significant in favour of Th. It is concluded that a moderate dose of CR-theophylline did not alter the sleep quality or substantially improve nocturnal oxygenation in patients with advanced COPD and mild to moderate day-time hypoxaemia. PMID- 1425868 TI - Factors in hydrazine formation from isoniazid by paediatric and adult tuberculosis patients. AB - An HPLC method is described for measurement of plasma hydrazine (Hz) concentrations (CHz) at the same time as isoniazid (INH) levels (CINH). Study has been made of CHz during 2-5 after dose in healthy adults (A, n = 34), in adult pulmonary TB patients (B, n = 18) and in paediatric tuberculous meningitis patients (C, n = 25). Although the population has about equal proportions of 'slow' (52%) and 'fast' acetylators, in none of the groups could a correlation be shown between CHz levels or rates of Hz accumulation and any measure of acetylator type. Consequently Hz must be derived both from INH and from its metabolites during the first hours post-dose. For group A and ca. 70% of groups B and C a constant and maximal fraction of dose (ca. 0.6% for adults and 0.4% for paediatric patients) appeared as Hz at 4-5 h. For group B patients small pre-dose concentrations increased with duration of treatment. Four patients in group B showed the highest levels of CHz and rates of Hz accumulation some three times greater than the rest; all four had been identified as alcoholics and one showed evidence of hepatotoxicity at CHz (5 h) = 1.3% of dose. Amongst group C (9/25) episodes of high CHz greater than 0.5% of dose occurred during the first weeks of treatment and one developed CHz ca. 100 ng/ml = 1.3% of dose coincidentally with indications of hepatic damage. PMID- 1425869 TI - Comparison of salivary miconazole concentrations after administration of a bioadhesive slow-release buccal tablet and an oral gel. AB - The salivary miconazole concentrations after administration of a bioadhesive slow release buccal tablet and an oral gel have been compared. The bioadhesive tablet consisted of a mixture of thermally modified starch and 5% polyacrylic acid. Although the amount of drug administered via the bioadhesive tablet was sixfold lower than when the gel was used, the salivary miconazole levels were higher and remained above the MIC value of Candida albicans for more than 10 hours. The mean adhesion time of the tablet was 586 min. The bioadhesive tablet appears to be a promising drug delivery system for the buccal administration of drugs for local therapy. PMID- 1425870 TI - The effects of omeprazole-induced hypochlorhydria on absorption of theophylline from a sustained-release formulation. AB - The present study was designed to investigate the effects of raised intragastric pH on the absorption of theophylline from a sustained-release formulation. Six healthy male volunteers participated in the cross-over randomised study and on one of two occasions were pretreated with 240 mg omeprazole, administered in three divided doses over the 22 h preceding the test. The sulphasalazine/sulphapyridine method of assessing oral-caecal transit time was implemented in order to assess upper bowel and colonic absorption. The mean fraction absorbed-time profile was calculated from serial serum theophylline concentration measurements by a modification of the Wagner-Nelson equation. During hypochlorhydria the mean oral-caecal transit time was 4.6 h, mean time to 90% absorption 6.8 h, and the percentage theophylline presumably to be absorbed from the colon 32.3. The corresponding values with normochlorhydria were, respectively, 3.8 h, 8.5 h, and 57.5%. The shorter oral-caecal transit time and lesser upper bowel absorption during normochlorhydria is postulated to result from motilin release due to duodenal acidification. Gastric hypoacidity resulted in significantly increased cumulative fractions of theophylline absorbed during a 3.5 h period, starting 0.5 h after breakfast. Possibly hypochlorhydria amplifies the increased motility which follows the intake of a meal, resulting in increased peristalsis and antiperistalsis, with more rapid drug absorption. PMID- 1425871 TI - Acipimox-induced facial skin flush: frequency, thermographic evaluation and relationship to plasma acipimox level. AB - Facial skin flush is the most frequent adverse effect induced by acipimox (ACX), a nicotinic acid analogue used in the management of hyperlipidaemia. The aims of the study were to evaluate the frequency, magnitude and reproducibility of the ACX flush in previously unexposed healthy subjects and to assess any possible relationship with the dose and plasma level of ACX. Seventy four healthy subjects received, on two different mornings, ACX 250 mg and placebo (P), according to a single blind, randomized, cross-over design; 33 had a clear flush after ACX and not after P.25 of those subjects were retested on five different mornings, with P, and with ACX 31.2, 62.5, 125.0, 250.0 mg, according to a double blind, randomized, cross-over design. Any increase in the local skin temperature was recorded by a thermocouple fixed to the left check. Subjective and objective assessment of the flush were strongly correlated with thermographic recordings. They indicated that a 120 min flush occurred after doses of ACX greater than 62.5 mg. In 12 of the 25 subjects, 6 with the highest and 6 with the lowest thermographic recordings, plasma ACX levels were determined. Subjects with different thermographic records had superimposable plasma ACX levels after all doses of ACX. Only the 6 subjects with the highest skin temperatures showed a significant relationship between the thermographic record and the plasma ACX. The data indicate that flush is a frequent, reproducible and dose-related adverse effect of ACX. PMID- 1425872 TI - The direct effects of diethylstilboestrol and nifedipine on the contractile responses of isolated human and rat detrusor muscles. AB - We have studied the direct effect of 2 mumol.l-1 diethylstilboestrol on isolated rat and human detrusor muscles. Diethylstilboestrol significantly reduced the amplitude of the contractile response of rat detrusor muscle to stimulation with acetylcholine, carbachol, electrical field stimulation, and 5-hydroxytryptamine. In isolated human bladder it also significantly reduced contractions stimulated with acetylcholine, carbachol, and electrical field stimulation. In depolarized rat detrusor muscle stimulated with different concentrations of calcium ions, the contractile responses were significantly reduced by the addition of diethylstilboestrol. Diethylstilboestrol also significantly reduced the amplitude of contractile response to potassium chloride. The inhibitory action of diethylstilboestrol was enhanced by the reduction of extracellular calcium ions, the maximum contractile response to acetylcholine, carbachol, and electrical field stimulation being reduced by a further 32%, 23%, and 45% respectively. Diethylstilboestrol did not have a significant effect on carbachol-induced contractions in depolarized rat detrusor muscle suspended in a calcium-free environment. Diethylstilboestrol was effective in blocking rat and human detrusor muscle contraction. The likely mechanism is a reduction of the influx of calcium ions into the cell during contraction rather than an effect on intracellular calcium release. These results give support for treating incontinent patients with drugs that block calcium ion uptake, and may suggest a further beneficial effect of oestrogen therapy in postmenopausal women. PMID- 1425873 TI - Dose-response relationship of topically applied methylprednisolone aceponate (MPA) in healthy volunteers. AB - Topical glucocorticosteroids are useful in the treatment of various skin diseases. Although many corticosteroids are available today, there is still a need for highly potent compounds with minimal adverse effects. Methylprednisolone aceponate (MPA) has recently been synthesized. Its activity has been evaluated using the vasoconstrictor assay and the poison ivy test (rhus dermatitis) in 19/20 healthy volunteers of either sex. Comparable blanching was found with MPA in a cream vehicle, in an ointment and a fatty ointment. Vasoconstriction and suppression of experimentally-induced poison ivy contact dermatitis were dose dependent in the concentration range 0.01% to 0.5% MPA. Concentrations of MPA of at least 0.05% were significantly active. Following the highest dose, blanching was close to the maximum which can be obtained. This finding, and the improvement of rhus dermatitis, suggest that MPA belongs to the highly potent local glucocorticosteroids. PMID- 1425874 TI - Pharmacokinetics of cyclosporine in hyperlipidaemic long-term survivors of heart transplantation. Lack of interaction with the lipid-lowering agent, fenofibrate. AB - Cyclosporine (Cy) binds to lipoproteins in plasma. In order to test if its pharmacokinetics would be modified when efficient lipid-lowering treatment is introduced, a study has been done of Cy pharmacokinetics and any interaction with the lipid-lowering agent fenofibrate in hyperlipidaemic long-term, survivors of heart transplantation. Fenofibrate 200 mg once daily significantly reduced blood lipids (cholesterol 6.5 vs 7.7 mmol/l; apoprotein B 1.2 vs 1.6 g/l) but did not modify mean whole blood Cy trough levels (113 before fenofibrate vs 103 ng.ml-1), Cmax (812 ng.ml-1 by RIA and 757 ng.ml-1 by HPLC before fenofibrate versus 865 and 741 respectively, during fenofibrate); tmax (1.6 and 1.7 h before fenofibrate versus 1.4 and 1.4 h respectively), and t1/2 (13.9 and 11.1 h versus 9.5 and 10.7 h). The only adverse effect was an increase in creatinine (157 vs 145 mmol/l). Further studies are needed to investigate the mechanism of Cy-fenofibrate nephrotoxicity and to evaluate the long-term efficiency and safety of fenofibrate after heart transplantation. PMID- 1425875 TI - Urinary caffeine metabolites in man. Age-dependent changes and pattern in various clinical situations. AB - In an exploratory study the 24-h urinary excretion pattern of caffeine and 14 of its major metabolites was studied in 32 volunteers (adults, adolescents and children), 14 patients either with end stage renal disease or liver cirrhosis, 7 heavy smokers and 27 patients on therapy with cimetidine, allopurinol, theophylline or phenytoin. Caffeine and its metabolites were quantified by UV absorption after liquid/liquid-extraction and HPLC-separation, which ensured proper analysis of 1-methyluric acid. In adults the renal excretion of caffeine derivatives corresponded to an intake of 509 mg caffeine/day, with 1-methyluric acid as the predominant metabolite. About 69% of caffeine was degraded by the paraxanthine pathway, and theobromine- (19%) and the theophylline pathway (14%) were less important. The ratio of paraxanthine formation to urinary caffeine concentration (= clearance equivalent) was about 2.2 ml.min-1.kg-1 in adults, and the corresponding ratios for theophylline and theobromine were 0.43 ml.min-1.kg-1 and 0.59 ml.min-1.kg-1, respectively. As expected, caffeine degradation was impaired in patients with cirrhosis and was increased in persons who smoked heavily or who were on phenytoin therapy. The results document the possibility of noninvasively investigating gross differences in caffeine disposition by analysis of the urinary pattern of its metabolites. PMID- 1425876 TI - Bacterial acetylation of 5-aminosalicylic acid in faecal suspensions cultured under aerobic and anaerobic conditions. AB - After oral administration of 5-aminosalicylic acid a substantial proportion of the acetylated form is excreted in the faeces. We have studied the role of the faecal microflora in acetylating 5-aminosalicylic acid. In faeces incubated under both aerobic and anaerobic conditions there was acetylation of 5-aminosalicylic acid. Of the anaerobic bacteria isolated from a 10(8) faecal dilution 44% were able to acetylate 5-aminosalicylic acid. We conclude that the normal faecal microflora contribute to the acetylation of 5-aminosalicylic acid. PMID- 1425877 TI - Increase in cerebrospinal fluid pressure in normocapnic volunteers in response to nalbuphine. AB - We have carried out a double-blind randomized study of the effect of nalbuphine (0.2 mg.kg-1 i.v.) or placebo on mean lumbar cerebrospinal fluid (CSF) pressure, mean cerebral perfusion pressure (CPP), transcutaneous PCO2 (tcPCO2), mean arterial blood pressure (MAP), and heart rate (HR) in 10 spontaneously breathing volunteers using invasive CSF pressure measurement. Nalbuphine increased CSF pressure from 9.2 mmHg to 16.4 mmHg and decreased CPP from 83.6 mmHg to 74.4 mmHg without significantly changing tcPCO2, MAP, or heart rate. In the placebo group there were no significant changes in CSF pressure, CPP, tcPCO2, MAP, or heart rate. These findings suggest that nalbuphine should be used with caution in patients at risk of intracranial hypertension. PMID- 1425878 TI - The effect of haemodialysis on the pharmacokinetics of tenoxicam in patients with end-stage renal disease. AB - We have studied the pharmacokinetics of tenoxicam after single and multiple oral doses of 20 mg in five patients (2 men and 3 women) with end-stage renal disease undergoing haemodialysis. After a single dose, tenoxicam had a half-life (t1/2) of 33 h, an apparent clearance (CL.f-1) of 4.3 ml.min-1, and an apparent volume of distribution (Vz.f-1) of 11.81. The maximum tenoxicam concentration (Cmax) was 4.3 mg.l-1 at a median tmax of 1.7 h. There were no significant differences between the values calculated from the pre- or post-dialyser port plasma samples. Tenoxicam plasma concentrations measured during once daily dosing before and after haemodialysis showed that tenoxicam does not accumulate. Our findings suggest that dosage adjustment may not be required in patients with end-stage renal disease on haemodialysis taking tenoxicam. PMID- 1425879 TI - Effect of single- and multiple-dose carbamazepine on the pharmacokinetics of diphenylhydantoin. AB - A three-phase trial has been done in 11 volunteers. They were given 600 mg phenytoin (Dilantin capsules) in each phase after an overnight fast. In the first study, phenytoin was given alone. In the second phase 400 mg carbamazepine (CBZ) was given at the same time as the phenytoin, and in the third part, 200 mg CBZ t.d.s. was given for one week prior to the phenytoin. Blood samples were taken for 72 h in each phase. Plasma levels of phenytoin and CBZ were determined by HPLC, and plasma protein binding was determined by equilibrium dialysis. The unbound fraction of phenytoin was 0.082, 0.085, and 0.077 in the control, single dose CBZ, multi-dose CBZ phases, respectively. Single and multiple doses of CBZ decreased the plasma level of phenytoin. The 72-h AUC of phenytoin was 276, 237, and 176 mg h.l-1 in the 3 phases, respectively, and the 72-h AUC of unbound phenytoin was 22.8, 20.5, 13.0 mg h.l-1. The AUC of phenytoin (unbound and total) after multiple doses of CBZ was significantly lower than in the other two phases. The apparent volume of distribution (Vz/f) was 89.9, 110.3, and 121.3 l in the 3 phases, respectively. Through pharmacokinetic analyses, the decreased AUC and increased Vz/f were attributed to decreased bioavailability of phenytoin when CBZ was co-administered. PMID- 1425880 TI - Lack of interaction of beta-methyldigoxin with ranitidine in patients with chronic congestive heart failure. PMID- 1425881 TI - Elevation of serum theophylline levels by ipriflavone in a patient with chronic obstructive pulmonary disease. PMID- 1425882 TI - Lack of pharmacokinetic interaction between moxonidine and hydrochlorothiazide. PMID- 1425883 TI - Bezafibrate lowers plasma lipids, fibrinogen and platelet aggregability in hypertriglyceridaemia. AB - The effects of bezafibrate 400 mg/day (slow release formulation) on plasma lipids/lipoproteins and on selected haemostatic parameters were evaluated in a double blind cross-over study in patients with Type IIb and IV hyperlipoproteinaemia. Placebo treatment did not influence any of those parameters, but the drug significantly reduced plasma triglycerides (-45%) and VLDL cholesterol, as well as causing a 12% fall in total cholesterol and a 20% increase in HDL cholesterol. Apo AI levels were significantly increased following bezafibrate and Apo B was reduced by about 20%. In addition to changes in the plasma lipid profile, bezafibrate reduced the sensitivity of platelets to the aggregatory effect of collagen, with no effect on TXB2 production. Fibrinogen levels after bezafibrate treatment were significantly lowered, the effect being more marked in patients with hyperfibrinogenaemia. Bezafibrate did not influence the plasma fibrinolytic profile. It is concluded that bezafibrate, besides its beneficial effects on the plasma lipoprotein profile, can exert beneficial changes on specific haemostatic parameters. PMID- 1425884 TI - Evaluation of lipid metabolism during antihypertensive treatment with nicardipine sr. AB - The antihypertensive and metabolic effects of oral nicardipine SR 40 mg b.i.d. have been studied in 18 (15 m, 3 f; age 52.7 y) hypertensives with mild hypercholesterolaemia, treated for 3 months after a 2 week period on placebo. An iv Fat Tolerance Test (FTT) was also performed in 8 patients following placebo, treatment with acute nicardipine 20 mg and chronic administration of nicardipine SR. There was a significant fall in BP from 160/97 on placebo to 147/87 after 3 months on nicardipine SR with no change in heart rate. Blood lipids did not change significantly. The disappearance rate of the lipid emulsion in the ivFTT showed no significant change (K2 was 1.93%/min after placebo, 1.84 after nicardipine 20 mg and 1.71 after chronic treatment). The results suggest that nicardipine is an effective antihypertensive drug and that it is devoid of untoward effects on lipid metabolism. PMID- 1425885 TI - Surrogate endpoints: a basis for a rational approach. AB - In clinical trials, the clinical endpoint is often replaced by an intermediate endpoint, known in some instances as a "surrogate" endpoint. The reasons for the substitution are often both practical and financial. At present, no theoretical basis or practical guidelines exist to help in the choice of surrogate endpoints. An approach is proposed here, based on three provisos which can be verified using one of a series of equations, if sufficient data on the pathophysiology and epidemiology of the disease are available. It is shown that even a strong statistical correlation is not a sufficient criterion for the definition of a surrogate endpoint. It is apparent that results obtained with the commonly used "surrogate" endpoints should be cautiously considered, and that the assessment of treatments should, when possible, be based on clinical rather than intermediate endpoints. PMID- 1425886 TI - Relationship between arterial and peripheral venous catecholamine plasma catecholamine concentrations during infusion of noradrenaline and adrenaline in healthy volunteers. AB - Noradrenaline and adrenaline were infused IV at 5 different rates (0.01-0.2 micrograms.kg.min-1) for 30 min to volunteers. The plasma catecholamine concentrations were determined by HPLC and electro-chemical detection. At the highest infusion rate, the arterial and venous plasma concentrations of noradrenaline increased from 1.18 to 44.1 nmol.l-1 and from 1.14 to 31.9 nmol.l 1, respectively, and of adrenaline from 0.29 to 23.9 nmol.l-1 and from 0.28 to 19.3 nmol.l-1, respectively. The peripheral venous plasma concentration of noradrenaline averaged 76% of the arterial concentration, and of adrenaline it was 73%. There was a linear relationship between the peripheral venous and arterial plasma noradrenaline and adrenaline concentrations at therapeutic doses. PMID- 1425887 TI - Lack of effect of mianserin on the symptoms of diabetic neuropathy. AB - The effect of the non-tricyclic antidepressant mianserin on symptoms of diabetic neuropathy has been studied in 18 patients in a double-blind, cross-over study with imipramine as a positive control. The patients were treated with placebo, mianserin, and imipramine, each for two weeks, in randomized order, with 1-3 weeks between the treatments. The symptoms were assessed by observer and self rating scales. Mianserin was given in the fixed dosage of 60 mg per day, whereas the dose of imipramine was adjusted to yield the optimal plasma concentration of imipramine plus desipramine of 400-600 nmol.l-1. The mianserin plus desmethylmianserin plasma concentration ranged from 85 to 850 nmol.l-1, with the highest concentration in a patient who was a poor metabolizer of both sparteine and mephenytoin. The symptoms of neuropathy were significantly reduced during imipramine treatment, although somewhat less than in earlier studies. In contrast, mianserin produced no change in symptoms in comparison with placebo. As there was no evidence that higher mianserin (plus metabolite) steady-state concentrations were associated with a more favourable effect, the negative outcome appeared not to be related to underdosing with mianserin. In contrast to drugs with documented effects on the symptoms of diabetic neuropathy, mianserin has a very weak or no inhibitory effect on 5-HT and noradrenaline reuptake and this may explain its poor clinical effect. PMID- 1425889 TI - Plasma protein binding of catecholamines, prazosin and propranolol in diabetes mellitus. AB - In the present study equilibrium dialysis has been used to determine the degree of protein binding of the catecholamines adrenaline and noradrenaline and the adrenergic receptor blockers, prazosin and propranolol in diabetics. The binding of the catecholamines in plasma from Type I and II diabetic patients was not significantly different from that of healthy subjects. The ratio of the bound and free catecholamine concentrations was correlated with the level of albumin (HSA). Significantly reduced protein binding of prazosin was observed in Type I and II diabetic subjects compared to healthy volunteers. The binding of propranolol was significantly reduced in Type I patients. The ratios between the bound and unbound concentrations of prazosin and propranolol were significantly correlated with the levels of alpha 1-acid glycoprotein (AAG). The results suggest that non enzymatic glycosylation of plasma proteins may increase the unbound fraction of the adrenergic blockers prazosin and propranolol. PMID- 1425888 TI - Effect of cigarette smoking and of a transdermal nicotine delivery system on glucoregulation in type 2 diabetes mellitus. AB - The effect of nicotine absorbed transdermally from a patch (TNS) and from cigarette smoking on insulin secretion and action in Type 2 diabetes has been compared. Twelve Type 2 diabetic smoking patients, aged 51 y, with diabetes for 9 y, treated either with diet and/or oral hypoglycaemic agents, were studied on three occasions, according to a double-blind, placebo-controlled, cross-over design. The subjects were investigated 12 h after their last cigarette or application of one patch of TNS 30 cm2 or TNS placebo, or whilst smoking their usual cigarette. Insulin secretion was assessed by a glucagon (1 mg IV) stimulation test. On a second occasion, insulin action was assessed by a hyperglycaemic-hyperinsulinaemic clamp, the spontaneous hyperglycaemia of the fasting state (8.61 mmol.l-1) being maintained during a 4 h insulin infusion (at 0.1 mU.kg-1.min-1 for the initial 2 h, and 1 mU.kg-1.min-1 during the last 2 h). TNS and the cigarette did not affect endogenous insulin secretion as compared to placebo. During the initial 2 h of the clamp study, plasma insulin increased from 88 to 155 pmol.l-1, hepatic glucose production (3-3H-glucose) was less suppressed after TNS (4.31 mumol.kg-1.min-1) than after placebo (2.5 mumol.kg-1.min-1), but was more suppressed than after cigarette smoking (5.61 mumol.kg-1.min-1). In the last 2 h of the clamp (plasma insulin 646 pmol.l-1), glucose utilization was less stimulated after TNS (36.1 mumol.kg-1.min-1) vs placebo (39.8 mumol.kg-1.min-1), but more than after cigarette smoking (33.6 mumol.kg-1.min-1), primarily because of a decrease in glucose storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425890 TI - Altered pharmacokinetics of lignocaine after epidural injection in type II diabetics. AB - The pharmacokinetics of lignocaine has been compared after epidural anaesthesia in diabetics and non-diabetic patients. Epidural lignocaine 8 mg.kg-1 was given to 8 well controlled Type II diabetic and 8 non-diabetic patients and the plasma drug concentration in serial blood samples were measured by HPLC. The plasma level of lignocaine was lower in diabetics compared to non-diabetics. The peak level was attained at 20 min in both groups. The clearance of the drug was significantly higher, (39.9 vs 16.7 ml.min-1.kg-1) associated with a decreased elimination half-life and mean residence time. The study suggests that the rate of absorption of lignocaine is not altered after epidural administration and that its hepatic metabolism is increased in diabetics compared to non-diabetics. PMID- 1425891 TI - Pharmacokinetic profile of a novel slow release preparation of molsidomine. AB - A novel slow release preparation containing 24 mg molsidomine has been investigated in 6 healthy subjects. Individual concentration/time-profiles after the tablet showed two separate concentration peaks at 2.2 h and 15.0 h. The relative bioavailability of the slow release preparation in comparison to an aqueous solution of molsidomine was 0.67. The in vivo dissolution profile revealed either a progressive decrease in dissolution velocity caused by altered physico-chemical conditions in the ileum and the colon or a progressive reduction in the absorption constant. In all subjects deconvolution revealed a punctual increase in absorption about 15 h post-dose, coinciding with the second peak of the concentration/time-profile. Therapeutic plasma levels of molsidomine (greater than 5 ng.ml-1) were not maintained over 24 h by this slow release formulation. PMID- 1425892 TI - Dose-dependent absorption of amoxicillin in patients with an ileostomy. AB - Amoxicillin was given as single doses of 375, 700, 1500, 3000 and 6000 mg an oral suspension to four volunteers with an ileostomy and with no active intestinal disease after an overnight fast. The excretion of amoxicillin and its penicilloic acid was followed in samples taken from the ileostomy and in urine produced over 6 h. Beta-lactamase activity was measured in ileal fluid and none was found. The percentage of the dose recovered from the ileostomy increased successively from 8% at the lowest dose to 77% at the highest dose. A complementary excretion pattern of amoxicillin was found in the urine, amounting to 70% recovery at the lowest dose to 23% at the highest dose. The results confirm the dose-dependence of the absorption of amoxicillin, which could at least in part be due to specialised absorption of this drug in humans. PMID- 1425894 TI - Pharmacokinetic estimations from microdialysis data. AB - Microdialysis has recently been adapted for sampling the extracellular fluid of various organs in order to measure drug concentrations, and the first clinical application has been published. My aim here is to provide simple rules about how to analyse pharmacokinetic data from such studies. The plotting of data on a time scale and the estimation of C (0) and slopes is not a trivial problem when multicompartmental models are assumed or sampling intervals are unequal. I have developed formulae and algorithms to solve the problem. A simple rule of thumb is given, suggesting when these formulae need to be applied. It is shown that the calculations of half-life and slopes is similar to standard methods for equal sample intervals and that calculation of AUC and clearance may be even more accurate for microdialysis data than for ordinary blood sampling, because of the time-integral character of the dialysis method. I have dealt with both zero-order and first-order kinetics. PMID- 1425893 TI - Nonlinearity of amoxicillin absorption kinetics in human. AB - Specialised gastrointestinal absorption of amoxicillin has been suggested in man and has been demonstrated in animals. In order to study the rate and extent of amoxicillin absorption, six healthy subjects were given 500 mg IV and two oral doses (500 mg and 3 g as a suspension). Absorption kinetics was analysed by compartmental modelling, noncompartmental methods and by calculation of absorption rates using deconvolution. Dose-dependency of the extent of amoxicillin absorption was observed, with a lower than expected mean maximum plasma concentration (49%), and fraction of the dose absorbed (39%) after the 3 g dose calculated from the 500 mg dose, assuming kinetic linearity. Zero-order kinetics of absorption was apparent in some subjects after the 500 mg dose, both from model fitting and absorption rate profile. However, no pattern consistent with pure first-order or zero-order absorption was observed after both oral doses in any individual. The dose-dependency of amoxicillin absorption was confirmed by a trend to an increased time of absorption for the high dose. The results show the variable nature and nonlinearity of the gastrointestinal absorption of amoxicillin and indicate the involvement of a number of factors, in addition to simple diffusion. PMID- 1425895 TI - Effect of age on the disposition of sodium fluoride. AB - Sodium fluoride (NaF) is used in the treatment of axial osteoporosis and so is mostly given to old patients. Since its pharmacokinetics has not been studied in the elderly, the pharmacokinetics of an enteric-coated tablet containing 50 mg NaF has been investigated in 15 aged inpatients (aged 65 to 75 y) and 12 young healthy volunteers (aged 21 to 26 y). The serum AUC of fluoride was 1.7-time higher in older than in younger subjects. There was a strong inverse correlation between the AUC and either body surface area (BSA) or glomerular filtration rate (GFR), both of which were very much lower in the elderly. This concluded that if efficacy or safety are related to the bioavailability of fluoride, it may be valuable to adjust the dosage of fluoride accordingly to the GFR and BSA. PMID- 1425896 TI - Time-dependent change in the effect of probucol in subjects with elevated cholesterol. AB - A time-dependent change in the cholesterol-lowering effect of probucol has been evaluated in 20 subjects with elevated cholesterol. Probucol 500 mg was given once daily at 07.00 h (day trial) or 19.00 h (night trial) for 3 months according to a crossover design. Fasting blood samples were obtained during the control period and at the end of each treatment period. Serum concentrations of total and HDL-cholesterol were significantly decreased by both the treatments with probucol [total cholesterol (mmol.l-1): control 6.58; day trial 5.41; night trial 5.10; HDL-cholesterol (mmol.l-1): control 1.35; day trial 1.06; night trial 0.96]. These parameters were significantly lower in the night trial than in the day trial. The data indicate that the cholesterol-lowering effect of probucol varies with its time of administration in subjects with elevated cholesterol. PMID- 1425897 TI - Effects of various prostaglandin synthesis inhibitors on the tone of the lower oesophageal sphincter in man. AB - The role of endogenous prostaglandins in the modulation of lower oesophageal sphincter (LES) function has been assessed by giving three structurally unrelated cyclooxygenase inhibitors and monitoring their acute effects on LES tonus and platelet thromboxane (TX) B2 production in 20 healthy volunteers. In a double blind, placebo-controlled, cross-over study, IV injection of soluble salts of acetylsalicylic acid and indomethacin elicited a transient increase in LES tonus of approximately 50% over baseline. A similar pattern was observed after the rectal administration of indomethacin. In contrast, indoprofen had no measurable effect on LES tones, despite comparable inhibition of platelet cyclooxygenase activity. This may have been due to the markedly different tissue distribution of the drug. The results suggest that endogenous prostaglandins physiologically exert an inhibitory influence on LES function. PMID- 1425898 TI - Effect of dipyridamole with or without aspirin on urine protein excretion in patients with membranous glomerulonephritis. AB - The antiproteinuric effect of the antiplatelet agent dipyridamole has been assessed after inhibition of thromboxane B2 (TxB2) synthesis in 8 patients with confirmed membranous glomerulonephritis. There were three study periods, each of 30 days, and 45 days apart, namely a washout period, treatment with dipyridamole 300 mg/d, and dipyridamole 225 mg/d plus aspirin 150 mg/d. On Days 1 and 30 of each study period serum and urine creatinine, 24-h excretion of protein, creatinine clearance, platelet aggregometry on whole blood and serum TxB2 were measured. Treatment with dipyridamole alone or with aspirin produced significant inhibition of platelet aggregation and a fall in 24-h protein excretion; the latter amounted to 54% with dipyridamole alone and 56% with dipyridamole plus aspirin (NS). Dipyridamole plus aspirin caused an 82% reduction in serum TxB2. PMID- 1425899 TI - Effects of thiopentone/suxamethonium on intraocular pressure after pretreatment with alfentanil. AB - The effects of pretreatment with alfentanil on intraocular pressure (IOP) were investigated in 40 patients undergoing ophthalmic surgery. Patients were randomly allocated to two study groups. Group 1 patients (n = 20) received alfentanil 15 micrograms.kg-1, vecuronium 0.01 mg.kg-1, thiopentone 3-4 mg.kg-1, and suxamethonium 1 mg.kg-1 for anaesthetic induction, whereas patients in group 2 (n = 20) received vecuronium 0.01 mg.kg-1, thiopentone 3-4 mg.kg-1, and suxamethonium 1 mg.kg-1. A total of seven measurements of intraocular pressure were taken in each patient, starting before premedication and ending after extubation of the trachea. In group 2 patients, there was an increase in IOP after endotracheal intubation. In group 1 patients, a decrease in IOP occurred which was related to the decrease in arterial blood pressure. We conclude that alfentanil pretreatment can prevent the increase in IOP following suxamethonium administration. PMID- 1425900 TI - Comparative bioavailability of two different rectal preparations of piroxicam in man. AB - A comparative pharmacokinetic study was performed with two types of suppository each containing 20 mg piroxicam. The bioavailability of piroxicam was studied in 24 healthy volunteers in a double blind, randomised, cross over study. No significant difference was found in the pharmacokinetic parameters [AUC(0-72 h), AUC, Cmax, t1/2 beta] calculated from plasma concentration time curves, indicating that the two preparations were bioequivalent. PMID- 1425901 TI - Medication utilization and patient information in homes for the aged. AB - A random cross-sectional sample of 198 residents was taken from a convenience sample of 20 Flemish, community-based nursing homes for the aged. Twenty trained interviewers reviewed the medication list of these residents and interviewed the nurses responsible for their daily care to assess their activities of daily living (ADL) and cognitive status. Direct interview was possible of 128 residents (65%); communication with the other 70 residents was impossible because of dementia (55 patients) or communication problems, such as aphasia and deafness (15 patients). An average of 4.5 different medicines was mentioned on the medication lists of the 198 residents. Drug use increases with age but stabilises after the age of 80 y. Medicines are ordered from local community pharmacies and are delivered to the ward rooms in original drug dispensing packs. The nursing staff is responsible for distribution inside the institution. Nursing personnel read the inserts of the medicines given to 98% of the residents and keep the inserts of 77% in the nursing office. Only 11% of the residents maintained some autonomy in ordering, keeping and taking their medication, although 42% were evaluated by the nurses as functionally and cognitively fit. Only 4% of the 128 residents able to respond to an interview had a notion of the potential adverse effects of their medication; the two most important sources of information about medicines mentioned by those residents were the general practitioner and the nursing personnel; 4% mentioned relatives and friends, or the pharmacist, as information sources. PMID- 1425902 TI - Chloroquine-induced pruritus and sickle cell gene trait in Africans: possible pharmacogenetic relationship. PMID- 1425903 TI - Analgesic drug prescription during the spondylodesis by the Harrington rod method. PMID- 1425905 TI - Human Golgi beta-galactoside alpha-2,6-sialyltransferase generates a group of sialylated B lymphocyte differentiation antigens. AB - The role of the human beta-galactoside alpha-2,6-sialyltransferase (hu alpha-2,6 ST) in the generation of B cell surface antigens was investigated by selecting subclones of COS cells (monkey kidney epithelial cells) constitutively expressing a transfected cDNA which encodes the hu alpha-2,6-ST (COS alpha-2,6-ST cells). Expression of hu alpha-2,6-ST in COS cells was sufficient to generate sialylated cell surface epitopes on different glycosylated antigens recognized by monoclonal antibodies to CDw75, CD76, and the unclustered monoclonal antibodies HB-4 and EBU 65. These epitopes were sensitive to sialidase treatment and are likely to contain terminal alpha-2,6-linked sialic acid residues. A novel antiserum raised against bacterially expressed hu alpha-2,6-ST fusion protein was used to localize the sialyltransferase in two cell lines with high expression of either endogenous (B cell line JOK-1) or recombinant (COS alpha-2,6-ST cells) hu alpha-2,6-ST. In both cell lines, the enzyme was detected only intracellularly in the juxtanuclear region and not on the cell surface. In contrast, CDw75, formerly proposed to be identical with an alpha-2,6-ectosialyltransferase, was strongly expressed on the cell surface. The different expression patterns show that neither the CDw75 antigen nor any of the other sialylated antigens analyzed is identical with the hu alpha-2,6-ST. Furthermore, the presence of a surface-expressed alpha-2,6-ST appears unlikely in these cell lines. We propose that CDw75, CD76, HB-4, and EBU 65 represent a unique group of B cell differentiation antigens the production of which requires the enzymatic activity of alpha-2,6-ST. PMID- 1425904 TI - Predominance of Th1-type T cells in synovial fluid of patients with Yersinia induced reactive arthritis. AB - The pathogenetic mechanisms underlying the development of reactive arthritis and the functional capacities of synovial T cells specific for Yersinia enterocolitica are still unclear. In this study we have determined the cytokine secretion patterns of 24 CD4+ synovial fluid (SF)-derived T cell clones from 2 patients with Yersinia-induced reactive arthritis, 16 clones specific for different Yersinia antigens and 8 clones as controls. The clones specific for Yersinia antigens predominantly belong to the T helper cell 1 (Th1) subset with production of interferon (IFN)-gamma and interleukin (IL)-2, but no IL-4, whereas SF T cells not reactive with Yersinia antigens produce IL-2, IL-4 and IFN-gamma and thus belonged to the Th0 subset. Moreover, short-term T cell lines established from SF and peripheral blood showed the same pattern. To further analyze the functional relevance of these data we investigated the influence of IFN-gamma and IL-4 on the intracellular killing of Yersinia in a human glioblastoma cell line. Our data show that the Th1 cytokine IFN-gamma promotes intracellular killing of Yersinia, whereas this effect is antagonized by the Th2 cytokine IL-4. Furthermore, the Th2 cytokine IL-10 inhibited the antigen-specific proliferative response and IFN-gamma and IL-2 production by the Th1 cells. These results provide insight into the antibacterial mechanisms at work in reactive arthritis after infection with Yersinia enterocolitica and, for the first time, reveal the cross-regulatory properties of cytokines derived from Th1 and Th2 cells in a human immune response to bacterial antigens. PMID- 1425906 TI - Interleukin-3-treated non-B, non-T cells switch activated B cells to IgG1/IgE synthesis. AB - The switch of activated B cells to IgE synthesis is an interleukin (IL)-3 dependent process. It is currently thought that specific T cells activated by antigen presented in the context of class II major histocompatibility complex are the major source of IL-4. Recently it has been demonstrated that a splenic non-T non-B cell population (termed NBNT) has the capacity to produce IL-4 following IgE and IgG receptor cross-linkage. In this study we demonstrate that IL-4 producing NBNT cells can induce the switch of lipopolysaccharide-activated B cells to the synthesis of IgG1 and IgE antibodies. Furthermore, it was found that not only IgE receptor cross-linkage but IL-3 was able to stimulate NBNT cells to produce IL-4 and induce the switch of B cells to IgE synthesis. NBNT cells derived from the spleen and bone marrow of SCID mice were able to produce IL-4 on exposure to IL-3. This suggested that the ability of IL-3 to stimulate IL-4 production was not dependent on prior exposure of the NBNT cells to antibody complexes in vivo. Taken together these findings represent the first observation that enough IL-4 is produced by NBNT cells to actually influence a B cell IgG/Ig response. The findings also clearly demonstrate that B cells do not need high concentrations of IL-4 to be directed to switch to IgG1 and IgE synthesis. PMID- 1425907 TI - Differentiation-specific expression of a novel G protein-coupled receptor from Burkitt's lymphoma. AB - Deregulation of the proto-oncogene MYC by specific chromosomal translocations has been shown to be essential but not sufficient for the development of Burkitt's lymphoma (BL). To identify other genes which either mark important steps in tumorigenesis or which reflect the cellular differentiation state of BL cells we have compared tumor cells to immortalized lymphoblastoid B cells by subtractive hybridization. We have identified a complementary DNA clone which encodes a novel member of the superfamily of GTP-binding (G) protein-coupled receptors, designated BLR1. The corresponding mRNA is expressed in BL and lymphatic tissues but not in other cell lines either of the B cell lineage or of other hematopoietic or non-hematopoietic origin. This exclusive expression of BLR1 and the oncogenic potential of this receptor class supports the hypothesis that BLR1 exerts a regulatory function in BL lymphomagenesis and/or B cell differentiation. Moreover, the protein sequence is highly related to that of receptors for the cytokine interleukin (IL)-8 and other neutrophil chemoattractants. We conclude that BLR1 may represent a potential candidate involved in the process of physiologic trafficking, cell-cell interactions, and activation of mature B lymphocytes in lymphatic tissues. PMID- 1425908 TI - Human growth factor for murine interleukin (IL)-9 responsive T cell lines: co induction with IL-6 in fibroblasts and identification as LIF/HILDA. AB - Two mouse helper T cell clones that proliferate in response to murine interleukin (IL)-9 could also be grown in conditioned medium of stimulated human connective tissue cells. The activity was not due to known T cell growth factors including human IL-9, which is not effective on mouse cells. This growth-stimulatory activity for TS1 cells (GATS) was co-induced with IL-6 on normal fibroblasts and certain sarcoma cell lines stimulated with IL-1, double-stranded RNA, virus or phorbol ester. However, the conditions for optimal induction and the kinetics of production were found to be different for IL-6 and GATS. GATS from phorbol ester stimulated human hepatosarcoma cells co-purified with IL-6, but could be separated from it by subsequent cation-exchange fast-protein liquid chromatography and reverse-phase high-performance liquid chromatography. Homogeneous tumor cell-derived GATS was a 25-kDa protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereas IL-6 produced by these cells appeared in its 23-kDa form. Pure GATS was found to be inactive in the B cell hybridoma growth assay for IL-6. Finally, GATS was identified by NH2-terminal sequence analysis of the mature protein as leukemia inhibitory factor or human interleukin for DA cells (LIF/HILDA). The effect of LIF/HILDA on T cells was not mediated by IL-2, IL-4 or IL-9 production. Since this cytokine has not previously been reported to act on T cells, further investigation of its role in T cell activation should be taken into consideration. PMID- 1425909 TI - High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo. AB - A patient with plasma cell leukemia was treated with anti-interleukin (IL)-6 monoclonal antibodies (mAb) for 2 months. Using chromatography on protein A Sepharose, anti-murine-IgG-Sepharose, anti-IL-6-mAb-Sepharose and gel filtration at pH 2.3, we have demonstrated that the anti-IL-6 mAb, by preventing the binding of IL-6 to its cell membrane receptor and its renal elimination, has induced huge amounts of IL-6 to circulate in the form of monomeric immune complexes. By using this observation, we have developed a mathematical modelling that allows the determination of the overall daily production of IL-6 in this patient, which was in the range of 15 micrograms per day. Overall in vivo production of cytokines has never been evaluated in animals or in humans before. PMID- 1425910 TI - Classical transplantation tolerance in the adult: the interaction between myeloablation and immunosuppression. AB - Allogeneic bone marrow transplantation in the neonate is an effective way of inducing permanent tolerance to donor tissue. To do the same in the immunocompetent adult requires immunosuppression to counter host-versus-graft alloreactivity. Conditioning with monoclonal antibodies (mAb) to CD4 and CD8 has been sufficient where donor and recipient are mismatched at only multiple "minor" histocompatibility loci, or at major histocompatibility complex (MHC) class I plus "minor" loci, but not where the mismatch involves the entire MHC. Tolerance across the MHC barrier requires extra conditioning with agents that happen to be both immunosuppressive and myeloablative, so obscuring the assessment of which effect is important. By using dimethylmyleran as a selective "space"-creating myeloablative agent, and CD4 plus CD8 mAb as sole immunosuppressive agents, we have been able to dissect the relative requirements for immunosuppression and myeloablation. We show here that transplantation tolerance could only be achieved when both types of agent were combined together so as to guarantee sufficient donor-type hemopoietic chimerism. We argue that the donor marrow, given sufficient space, will engraft and provide a sustained source of tolerogen overriding any host resistance that antibodies cannot control. PMID- 1425911 TI - Expression and biological activity of interleukin-1 receptors in mouse gamma/delta thymocytes during ontogeny. AB - We have recently shown that the response of mouse thymocytes to interleukin (IL) 1 + IL-2 was maximal at birth and that the responding cells displayed a CD4-CD8- T cell receptor (TcR) gamma/delta + phenotype. Unexpectedly, despite their high proportion of gamma/delta + cells, fetal thymocyte populations responded only weakly to IL-1 + IL-2. In this report, we demonstrate that the discrepancy between the day 17.5 fetal and newborn sensitivities to the combined action of IL 1 and IL-2 is a consequence of the different patterns of high-affinity IL-1 receptor (IL-1R) expression displayed by these two cell subsets. Actually, high- and low-affinity IL-1R are found in TcR gamma/delta + newborn cells and, in contrast, only low-affinity IL-1R are detectable in day 17.5 fetal cells. Our binding and functional studies strongly support the hypothesis that high-affinity IL-1R on the one hand, and low-affinity ones on the other hand, are involved in the response to IL-1 + IL-2 of newborn and day 17.5 fetal thymocytes, respectively. In addition, the high-affinity IL-1R appear to be far more efficient than the low-affinity receptors in promoting IL-2 responsiveness of thymocytes. PMID- 1425912 TI - In vivo administration of interleukin-2 turns on anergic self-reactive T cells and leads to autoimmune disease. AB - One major mechanism of self tolerance involves the deletion of T cell clones in the thymus. In athymic mice, tolerance to self antigens must be generated extrathymically. T cells with self-reactive receptors undergo either peripheral clonal deletion or become unresponsive (i.e. anergic). The unresponsive state of human and mouse T cell clones in vitro can be reversed by the addition of exogenous interleukin (IL)-2, thus transforming anergic T cells to an activated state. Here it is shown that the in vivo delivery of IL-2 to athymic BALB/c nu/nu mice abrogates the anergic state of self-reactive V beta 3+ and V beta 11+ T cells [which are normally deleted in the minor lymphocyte stimulatory (Mls)-1b-, I-E(+)-expressing euthymic counterparts]. Thus, V beta 3+ and V beta 11+ T cells from IL-2-treated nude mice proliferate in response to T cell receptor cross linking and acquire effector functions as measured by their ability to deliver aid to B cells upon specific stimulation. This activation correlates with the development of autoimmune manifestations (DNA autoantibodies, rheumatoid factors, erythroleukopenia and minimal change nephritis) in these IL-2-treated mice. PMID- 1425913 TI - Interferon-gamma induced lethality in the late phase of Plasmodium vinckei malaria despite effective parasite clearance by chloroquine. AB - A combination therapy was tested consisting of chloroquine and interferon-gamma (IFN-gamma) in the late phase of blood-stage Plasmodium vinckei malaria in BALB/c mice. When mice were treated with three times 300 micrograms chloroquine at 24-h intervals starting at a parasitemia of 30%-50%, only 5 of 14 mice (36%) died 2-4 days after initiation of therapy. However, when infected mice received chloroquine plus 1 microgram IFN-gamma at the same time, 14 of 18 mice (78%) died 0.5-3 days after start of therapy (p < 0.05) despite clearance of parasitemia. The histopathology from mice dying after combination therapy revealed interstitial leukocyte infiltration of lung tissue, severe liver cell necrosis and kidney tubular necrosis. Pretreatment of P. vinckei-infected mice with pentoxifylline, a phosphodiesterase inhibitor, led to a significant decrease of IFN-gamma-induced lethality (p < 0.05). In contrast, pretreatment with neutralizing antibodies to tumor necrosis factor or with L-N-monomethyl arginine, the latter an inhibitor of the nitric oxide synthase, significantly increased lethality (p < 0.05). PMID- 1425914 TI - Molecular analysis of anti-idiotypic monoclonal antibodies in the HLA-DR antigenic system. AB - The structural organization of anti-idiotypic (id) antibodies has been investigated mostly in haptenic systems. No information is available about the structural characteristics of anti-id antibodies in major histocompatibility complex (MHC) antigenic systems, although these data may contribute to our understanding of the molecular basis of their functional role in the immune response. Therefore, we have determined the nucleotide and derived amino acid sequence of the VH and VL regions of the anti-id monoclonal antibodies (mAb) F5 444, F5-830, F5-963, F5-1126, F5-1336 and F5-1419, which had been elicited with the syngeneic anti-HLA-DR1, 4, w14, w8, 9 mAb AC1.59. The six anti-id mAb are heterogenous in their VH and VL region gene usage. This structural heterogeneity is not correlated with their target specificity and with their ability to elicit anti-HLA-DR antibodies. The latter characteristic is markedly influenced by a limited number of amino acid substitutions, since mAb F5-444, which induces anti HLA-DR antibodies, differs only in two residues in complementarity-determining regions and in five residues in framework regions from mAb F5-1126, which does not induce anti-HLA-DR antibodies. The heterogeneity in VH and VL region gene usage by the six anti-id mAb in the HLA-DR system is at variance with the restricted VH and VL region gene usage by syngeneic anti-id mAb in several haptenic systems. Furthermore, at variance with haptenic systems, the primary structure of the D segments of the anti-id mAb is not correlated with their ability to induce anti-HLA-DR antibodies. On the other hand, the frequency of D-D fusion events underlying the derivation of the D segments of the six anti-id mAb in the HLA-DR system and their average length are similar to those found in anti id mAb in haptenic systems. In addition, like in the latter systems, somatic mutations appear to contribute to the generation of diversity of anti-id mAb in the HLA-DR system. PMID- 1425915 TI - Molecular characterization of the V gamma 9 T cell receptor repertoire expressed in patients with rheumatoid arthritis. AB - We have characterized the variable (V)gamma 9 T cell receptor (TcR) repertoire expressed in synovial membrane (SMC) and peripheral blood mononuclear cells (PBMC) of five rheumatoid arthritis (RA) patients. The experimental approach was to sequence the junctional regions of polymerase chain reaction (PCR)-amplified V gamma 9 transcripts; gamma chain sequences were compared with those found in normal PBMC. For normal PBMC, a large proportion of V gamma 9 transcripts used the joining (J)gamma P gene segment whereas a few used J gamma 2. Despite this restriction in J gamma usage, there was extensive junctional region diversity with a unique sequence observed in each transcript examined. In contrast to normal PBMC, J gamma usage of V gamma 9 transcripts in PBMC of two patients was skewed towards J gamma 2. This deviation in J gamma usage was more pronounced in SMC since all patients expressed V gamma 9 transcripts in SMC which predominantly used J gamma 2, as opposed to J gamma P in normal PBMC. Further, approximately 60% of V gamma 9 transcripts in PBMC of each of three patients had identical junctional region sequences, although the specific sequences were unique in each patient. For two of these patients the dominant transcript found in the PBMC was detected in the corresponding SMC at about 10% and 40%, respectively. Overall, our findings indicate that V gamma 9-bearing T cells in RA peripheral blood are largely derived from clonal expansion whereas in the synovium there is expression of a population of these cells that are mainly polyclonal. This may reflect in vivo expansion in response to a V gamma 9/J gamma 2 region-specific antigen. The data presented in this report suggest that V gamma 9+ T cells may play a role in the development of RA. PMID- 1425916 TI - Signal transduction for interleukin-3-dependent leukotriene synthesis in normal human basophils: opposing role of tyrosine kinase and protein kinase. AB - The intracellular signaling pathways regulating the synthesis of leukotrienes by myeloid cells are largely unknown. In addition, the signal transduction mechanisms utilized by the cytokine receptor family are still poorly understood. The fact that in mature human basophils the synthesis of leukotriene C4 (LTC4) induced by C5a is strictly dependent on a short preincubation with the cytokine interleukin-3 (IL-3), allowed us to investigate the metabolic requirements for LTC4 synthesis, and also to provide some information on early signal transduction mechanisms of IL-3 in these differentiated, non-dividing blood leukocytes. IL-3 itself does not alter intracellular free calcium concentration ([Ca2+]i) in basophils, whereas C5a induces a transient rise independent of IL-3 pretreatment, indicating that the priming effect of IL-3 cannot be explained by alterations in [Ca2+]i changes. The protein kinase C inhibitor staurosporine did not inhibit C5a induced histamine release nor IL-3-dependent LTC4 formation in contrast to the IgE receptor-dependent basophil response. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) induced histamine release without leukotriene formation. PMA-treated basophils did not produce LTC4 in response to C5a. Rather, PMA blocked the IL-3 effect on C5a-induced LTC4 synthesis. Only the C5a signal but not the IL-3 effect was pertussis toxin sensitive. Two unrelated tyrosine kinase inhibitors, tyrphostin RG-50864 and herbimycin A, were both very efficient blockers of IL-3-dependent lipid mediator formation whereas C5a-induced histamine release was preserved. Thus LTC4 formation does not require activation of a staurosporine-sensitive serine/threonine kinase. To the contrary, IL-3 dependent LTC4 formation appears to be regulated by serine/threonine and tyrosine phosphorylation in an antagonistic manner. PMID- 1425917 TI - Antigen presentation for T cell interleukin-2 secretion is a late acquisition of neonatal B cells. AB - The ability of B lymphocytes to process and present antigen to helper T cells is essential to initiate T cell-B cell interactions in humoral immune responses. Here we describe the developmental acquisition of the antigen-presenting function of B cells as measured by the ability of B cells to stimulate a T cell hybrid to interleukin (IL)-2 secretion. Neonatal splenic B cells are not adult-like in their ability to process and present the model protein antigen pigeon cytochrome (Pc), which enters the B cell through fluid-phase pinocytosis, until 21 to 28 days of life. The ability of neonatal B cells to process and present antigen which enters the cell bound to surface Ig is not adult-like until 28 days of age. When neonatal B cells acquire antigen-presenting cell (APC) function, surface IgM facilitates antigen processing. The delayed acquisition of APC function cannot be accounted for solely by a deficiency in major histocompatibility complex MHC class II, ICAM-1, or LFA-1 as neonatal B cells express adult levels of these molecules by 7-14 days after birth. Moreover, the ability of neonatal B cells to present a peptide fragment of Pc which does not require processing is adult like by day 14. Furthermore, neonatal B cells are capable of binding, internalizing and degrading radiolabeled antigen, suggesting a more subtle level of regulation. In contrast to neonatal B cells, immature B cells in the adult bone marrow and adult B cells undergoing antigen-driven differentiation to memory B cells, as defined by the loss of the J11D marker, are competent to process and present antigen resulting in T cell IL-2 secretion. Thus, developing B cell subpopulations in the adult and in the neonate can be distinguished. Only neonatal B cells are deficient in their ability to stimulate T cells to IL-2 production. PMID- 1425918 TI - Expression and role of interleukin-2 receptor beta chain on CD4-CD8- T cell receptor alpha beta+ cells [corrected]. AB - Using anti-murine interleukin-2 receptor beta chain (IL-2R beta) monoclonal antibody (mAb), we have examined the expression of IL-2R beta on murine thymocyte subpopulations. We found that it was constitutively expressed on 1%-4% of thymocytes in an almost mutually exclusive fashion with IL-2R alpha. The expression of IL-2R beta is developmentally regulated. While it is expressed mainly on T cell receptor gamma delta+ (TcR gamma delta+) cells during fetal age, the major subpopulation expressing IL-2R beta in adult mouse shifts to CD4-CD8 TcR alpha beta+ thymocytes. A considerable portion of CD4-CD8- TcR alpha beta+ cells in other organs, including spleen, bone marrow and liver, was also found to express IL-2R beta. In fetal thymus organ culture, the above thymocyte subset was induced to expand in response to exogeneous IL-2, and the expansion was inhibited by addition of anti-IL-2R beta mAb, suggesting that IL-2R beta is functional in this subpopulation. However, in vivo blockade of the IL-2/IL-2R pathway with the mAb did not exert any effects on the appearance of CD4-CD8- TcR alpha beta+ cells both in the thymus and the periphery. This indicates that the development of CD4 CD8- TcR alpha beta+ cells is not solely controlled by IL-2 but also by other complex elements. PMID- 1425919 TI - Cloning and sequence analysis of two isotypic IgM heavy chain genes from Atlantic salmon, Salmo salar L. AB - A leukocyte cDNA library from Atlantic salmon, based on oligo-dT priming, was constructed in lambda-gt10. Immunoglobulin heavy chain (IgH) cDNA were isolated from the library using a specific probe generated by polymerase chain reaction (PCR) between two conserved areas within the variable region (second and fourth frame region). Two cDNA clones encoding the entire constant region of membrane bound IgH, and one cDNA encoding the entire constant region of secretory IgH were sequenced, revealing messages from two isotypic IgM genes. Both genes were shown to be present in haploid embryos and have been isolated from a genomic library, the exons and deduced amino acid sequences of which are presented here (salmon CHA and CHB). The splicing of transcripts encoding the membrane-bound IgH excises the whole fourth exon as in other teleosts. The nucleotide and amino acid identity between salmon CHA and CHB are 98.2%, and 96.2%, respectively. Two subfractions of IgM from Atlantic salmon separated by ion chromatography can be explained by a net exchange of basic residues in salmon CHB compared to CHA. The finding of two closely related salmon CH genes is in accordance with the quasi tetraploid state of the Atlantic salmon genome. PMID- 1425920 TI - Expression of interleukin (IL)-1 beta, IL-6 and their respective receptors in the normal rat brain and after injury. AB - The expression of interleukin (IL)-1 beta, IL-6 and their respective receptors has been studied in the rat brain before and up to 24 h after injury. Messenger RNA transcripts of these four genes were detected by in situ hybridization (ISH) in different structures of the intact brain. The distribution was very similar for IL-1 beta, IL-6 and IL-6 receptor (IL-6R). The expression of IL-1R was more widespread. Within hours after injury, an increased expression of IL-1 beta, and thereafter of IL-6 was documented. The expression of IL-1R and IL-6R was also increased. This expression was bilateral and not restricted to the injured area. Within 24 h, all ISH patterns had returned to normal. The molecular data were confirmed by protein data. Indeed, the distribution of IL-6 (detected by immunocytochemistry) agreed with the ISH patterns for IL-6. Furthermore, extracellular fluid was collected by microdialysis at the site of the lesion during 12 h and successive fractions were assayed for the presence of bioactive IL-1 and IL-6. Increases in IL-1 and later in IL-6 levels were detected. The rapid and concomitant increased expression of IL-1 beta, IL-6 and their receptors after injury stresses their possible early role in inflammatory mechanisms also in the brain, before any recruitment of inflammatory cells from remote nervous and not nervous areas. PMID- 1425921 TI - Cloning and sequences of primate CD4 molecules: diversity of the cellular receptor for simian immunodeficiency virus/human immunodeficiency virus. AB - To study the interaction between the primate lentiviruses simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) and the CD4 receptor we have cloned and sequenced the CD4 molecule from six non-human primate species: African green monkeys (three subspecies: sabeus, pytherethrus, aethiops), sooty mangabeys, patas monkeys, chimpanzees, rhesus macaques, and pig-tail macaques. Molecular cDNA clones representing CD4 mRNA were generated from total RNA from peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR) amplification including reverse transcriptase in initial reactions followed by two rounds of nested amplifications. Primer sequences were selected from regions conserved among human and rodent CD4 genes. Alignments of deduced amino acid sequences revealed interesting findings. First, all of the primate CD4 molecules were about 90% identical to the human CD4 sequence except the chimpanzee (98%). Second, two macaques or two African green monkey subspecies were as distanly related as the human versus chimpanzee sequences. Third, relatedness of CD4 sequences could not be predicted on the basis of geographic origin (Asian vs. African). Finally, upon sequencing several clones from individual monkeys, a low degree of sequence variation (nucleotide substitutions, deletions, and insertions) was found within the same animal, and in case of sooty mangabeys two distict populations of CD4 molecules were present within three of four individuals. The distinguishing features involved eight amino acid changes, including a single lysine deletion relative to a primate consensus sequence in the first complementary-determing region of V1J1. These two CD4 populations were present also at the genomic DNA level and may arrive from the two chromosomal alleles, suggesting the existence of distinct sooty mangabey subspecies. Overall, the V1J1 and to a lesser extent V2J2 were the most variable regions among the sequences examined. By construction and expression in mammalian cell lines of CD4 chimeras in which these regions of the human CD4 were replaced by those of the African green monkey and pig-tail macaques, a higher molecular mass of the CD4 chimeras were obtained in sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the additional N-linked glycosylation sites present in these monkey CD4 are also used. PMID- 1425922 TI - Heat shock prevents lipopolysaccharide-induced tumor necrosis factor-alpha synthesis by rat mononuclear phagocytes. AB - Tumor necrosis factor-alpha (TNF-alpha), a mononuclear phagocyte-derived peptide is known to participate in the pathogenesis of fever. To determine whether a feedback mechanism exists by which elevated temperatures influence TNF-alpha generation, we have examined the effects of heat shock on the in vitro synthesis of TNF-alpha by rat glomeruli, inflammatory peritoneal macrophages and blood monocytes. Preexposure of peritoneal macrophages to elevated temperatures for 20 min decreased the subsequent lipopolysaccharide-induced release of TNF-alpha bioactivity. The mean reductions were 11.9 +/- 5.0%, 86.3 +/- 12.0%, and 95.2 +/- 3.5% after pretreatment at 39, 41 and 43 degrees C, respectively. Reductions, that were transient, were maximum when lipopolysaccharide was added 0-2 h after heat shock. They correlated with the decreased release of immunoreactive TNF alpha and the decreased expression of both cell-associated TNF-alpha molecule and TNF-alpha mRNA. Heat shock-induced inhibition of TNF-alpha release was independent of variations of prostaglandin synthesis, but was possibly related to the induction of heat-shock proteins since (a) macrophages exposed to heat shock synthesized the major 70- and 90-kDa heat-shock proteins, and (b) chemical inducers of the heat-shock response were also effective inhibitors of TNF-alpha release. The mean reduction of TNF-alpha release after pretreatment at 41 degrees C was found to be identical in glomerular tissue (82.0 +/- 7.5%), but significantly less in blood monocytes (43.9 +/- 10.9%). This supports the hypothesis that a negative-feedback mechanism exists between elevated temperature and lipopolysaccharide-induced TNF-alpha synthesis, and suggests that this regulation is less active in blood monocytes than in tissue macrophages. PMID- 1425923 TI - Altered major histocompatibility complex-restricted antigen recognition by T cells from elderly humans. AB - Positive selection of T cells within the thymus gland leads to major histocompatibility complex (MHC)-restricted recognition of antigen by T lymphocytes. As the thymus gland involutes with age, altered MHC-restricted antigen recognition by T cells from elderly humans would be expected. We have tested this hypothesis by comparing the proliferative response of T cells and T cell clones from aged and young subjects to influenza determinants presented by autologous or allogeneic antigen-presenting cells (APC). Under conditions in which the allogeneic mixed lymphocyte reaction was minimal, T cells from six of seven aged donors but only one of seven young donors were stimulated by influenza vaccine presented by allogeneic APC. More importantly, one-half of the influenza specific T cell clones derived from aged donors, but none of the clones derived from young donors, were activated by influenza vaccine presented by allogeneic APC. While 80% of the MHC-nonrestricted influenza-specific T cell clones expressed the gamma/delta T cell receptor, 20% of these clones expressed the alpha/beta T cell receptor. Thus, changes in MHC-restricted antigen recognition by T cells and in altered distribution of alpha/beta versus the gamma/delta T cell receptor bearing antigen-specific T cell clones occur with aging. PMID- 1425924 TI - Functional and molecular characterization of single, (4-hydroxy-3 nitrophenyl)acetyl (NP)-specific, IgG1+ B cells from antibody-secreting and memory B cell pathways in the C57BL/6 immune response to NP. AB - We have used multiparameter flow cytometry to identify a population of IgG1+ IgM- antigen-specific B cells which emerges in spleens of C57BL/6 mice following immunization with the hapten, (4-hydroxy-3-nitrophenyl)acetyl (NP). Characterization of the specificities of IgG1 antibodies produced by single, sorted IgG1+ NP+ cells in both Elispot assays and in microcultures containing lipopolysaccharide, interleukin (IL)-2, IL-4 and IL-5 indicates that the splenic IgG1+ NP+ B cell population includes both IgG1 anti-NP antibody-secreting cells and non-secreting, IgG1+ memory B cells. Each functionally discrete population of IgG1+ B cells expresses a distinctive surface phenotype defined by a wide range of B cell markers. In particular, antibody-secreting, IgG1+ cells were uniquely identified by co-expression of the matrix receptor, syndecan. The NP-specific B cell population emerging in the day 7 primary response was assessed for clonotypic diversity by amplification and direct sequencing of the rearranged V186.2 heavy chain variable region gene expressed by single, ex vivo IgG1+ NP+ lambda+ B cells. Memory B cell clones, distinguished by junctional diversity, carried either no mutation or a single mutation within rearranged V186.2, suggesting isolation of these cells at the onset of the hypermutation mechanism. This novel approach, therefore, allows the direct and unambiguous identification and characterization of individual B cell clonotypes during their initial selection and activation in antibody responses in vivo. PMID- 1425925 TI - Mechanisms of induction of primary virus-specific cytotoxic T lymphocyte responses. AB - We have investigated the ability of various antigen-presenting cell (APC) types to induce primary anti-viral cytotoxic T lymphocyte (CTL) responses by single in vitro stimulation. Of these APC types, only dendritic cells (DC) and RMA-S lymphoma cells could induce primary CTL responses, but by divergent mechanisms. DC were capable of generating primary virus-specific CTL, either by presenting viral peptide or processed infectious virus. In contrast, RMA-S cells could not present endogenous antigen, e.g. after virus infection, but this cell line very efficiently presented exogenous viral peptides to induce primary virus-specific CTL in vitro. Spleen cells, lipopolysaccharide-induced B cell blasts or the non mutated RMA cells did not have the ability to trigger unprimed T cells by single in vitro stimulation. We have investigated several characteristics important for primary CTL response induction by DC and RMA-S cells (summarized in Fig. 6). Primary CTL response induction by DC or RMA-S cells was blocked by anti-LFA-1 or anti-CD8 monoclonal antibodies (mAb). DC rapidly aggregated with unprimed T cells, which was independent of LFA-1 and CD8 molecules. RMA-S cells did not form conjugates with unprimed T cells. Despite their abundant major histocompatibility complex (MHC) class I cell-surface expression, DC did not bind much exogenously added viral peptide. In contrast, the MHC class I molecules on RMA-S cells bound a large quantity of exogenously administered peptide. Powerful adhesion by DC and high expression of relevant MHC/peptide complexes on RMA-S cells are important features in the initial contact with unprimed T lymphocytes. In a later stage of contact, both DC and RMA-S cells activate LFA-1 (and CD8) molecules at the T cell surface to strengthen and maintain the contact between T cell and APC. PMID- 1425926 TI - Selective and differential binding of interleukin (IL)-1 alpha, IL-1 beta, IL-2 and IL-6 to glycosaminoglycans. AB - The binding of interleukin (IL)-1 alpha, IL-1 beta, IL-2 and IL-6 to acidic polysaccharides was investigated by affinity chromatography of the recombinant, radioiodinated interleukins on columns of immobilized polysaccharide. Each interleukin showed selective binding retention. Overall heparin bound all four interleukins significantly, whereas chondroitin sulfate provided little retention. IL-1 alpha and IL-1 beta showed differential binding, with only the latter binding to hyaluronic acid. IL-2 was virtually completely retained on fucoidan. Noniodinated recombinant IL-2 bound similarly to fucoidan, and fucoidan was found to sequester IL-2 activity in a bioassay employing IL-2-dependent CTLL cells. In all other cases tested, interleukin retention was partial, implying that interleukin binding sites are sparsely distributed along the polysaccharide chains. These findings suggest that during the immune response, interleukins will tend to be retained at sites of secretion by interaction with glycosaminoglycans in the extracellular matrix and on cell surfaces. PMID- 1425927 TI - Alpha heavy chain disease alpha mRNA contain nucleotide sequences of unknown origins. AB - Human alpha heavy chain disease is characterized by the production of abnormally short alpha IgH chains. In previously published cases it has been found that the malignant cells produce abnormal alpha mRNA, lacking VH and CH1 sequences and composed of a leader sequence peptide, sequences of variable length (69 to 84 bp) and of unknown origin, followed by normal CH2 and CH3 sequences. In this study we established the nucleotide sequence of alpha mRNA for six cases of alpha heavy chain disease. We observed that all six alpha mRNA lack the VH and CH1 sequences as do those previously described. They also contain in-frame inserts of unknown origin between the leader peptide and the normal CH2 and CH3 coding sequences. These inserts are of variable length (42 to 105 bp) and they are unrelated. These results suggest the existence of a common mechanism defect leading to deletions/insertions in alpha heavy chain disease rather than a specific interaction between alpha 1 IgH gene with a unique defined molecular species. PMID- 1425928 TI - Effects of acute and chronic fenfluramine on self-stimulation and its facilitation by amphetamine. AB - DL-Fenfluramine (20 mg/kg) releasing serotonin and amphetamine (2 mg/kg) releasing dopamine were given to adult rats trained to bar press for electrical stimulation to the medial forebrain bundle. Amphetamine treatment enhanced lever pressing for 1-2 h. A single fenfluramine treatment rapidly suppressed self stimulation with slow recovery in 5-7 days to a rate below the initial basal rate. A second treatment a week later again suppressed response rate and rates returned to a still lower baseline. Combined fenfluramine-amphetamine treatment at this time transiently abolished lever pressing for 1-3 h followed by 9-11 h of enhanced responding. The serotonin antagonist, ketanserine (0.1 mg/kg), but not cyproheptadine (0.1 mg/kg i.p.), partially protected against the effects of fenfluramine. The serotonin agonist, quipazine (0.5 mg/kg), but not dimethoxyiodophenylisopropylamine (DOI) (2.2 mg/kg), partially substituted for fenfluramine in the combined treatment. Fenfluramine markedly depleted serotonin and 5-hydroxyindoleacetic acid in frontal cortex, hippocampus, and caudate putamen. Ventral and midline midbrain regions were less affected. Combined fenfluramine and amphetamine treatment elevated dopamine levels in frontal cortex, hippocampus and caudate-putamen, but not in midbrain. These findings support a serotonin-dopamine interaction in self-stimulation behavior and suggest that repeated fenfluramine treatment results in chronic low level serotonergic stimulation and diminished serotonin storage capacity. PMID- 1425929 TI - The novel 5-HT1A receptor antagonist (S)-UH-301 prevents (R)-8-OH-DPAT-induced decrease in interstitial concentrations of serotonin in the rat hippocampus. AB - Previous studies have demonstrated that the novel 8-OH-DPAT (8-hydroxy-2-(di-n propylamino)tetralin) analogue (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin ((S)-UH-301) is able to antagonize several behavioural and biochemical effects of the 5-HT1A receptor agonist 8-OH-DPAT in the rat. In the present study in vivo microdialysis was used to evaluate the effects of (S)-UH-301 on interstitial concentrations of 5-hydroxytryptamine (5-HT), its metabolite 5 hydroxyindoloacetic acid (5-HIAA), and the catecholamine metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the dorsal hippocampus of freely moving rats. Furthermore, the effects of (S)-UH-301 on (R) 8-OH-DPAT-induced changes in dialysate hippocampal concentrations of 5-HT and metabolites were examined. Neither 5-HT nor metabolites were significantly influenced by (S)-UH-301 (1.25, 2.5, 5.0 mg/kg s.c.). In contrast, (R)-8-OH-DPAT (100 micrograms/kg s.c.) decreased interstitial concentrations of 5-HT (to 45% of baseline) and 5-HIAA (to 75%), and increased concentrations of DOPAC (to 165%) and HVA (to 155%). Pretreatment with (S)-UH-301 (2.5 mg/kg s.c.) 20 min before (R)-8-OH-DPAT (100 micrograms/kg s.c.) abolished the 5-HT and metabolite response to (R)-8-OH-DPAT. These data indicate that (S)-UH-301 is able to antagonize (R)-8 OH-DPAT-induced biochemical effects in vivo without producing any effects when given alone. Thus, the present study contributes to the characterization of (S) UH-301 as a 5-HT1A receptor antagonist with low intrinsic activity. PMID- 1425930 TI - Inhibition by heparin of platelet activation induced by neutrophil-derived cathepsin G. AB - Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombotic activity of this drug. The present study shows that different heparin preparations (50 nM) completely prevent human platelet aggregation, serotonin release and thromboxane B2 production induced by purified neutrophil derived cathepsin G (E.C. No. 3.4.21.20). This inhibitory effect was not related to the anticoagulant property of the compounds, since a heparin preparation with an inactivated active for antithrombin III was also effective. Heparins inhibited the protease activity of the enzyme over the same range of concentrations. Since the effect of cathepsin G on platelets requires an intact proteolytic active site, the inhibitory effect of the drugs on cathepsin G-induced platelet activation may be explained by a blockade of protease activity. Heparins were also shown to reduce platelet activation induced by cathepsin G released from activated polymorphonuclear leucocytes in mixed cell suspensions. As polymorphonuclear leucocytes might contribute to both arterial and venous thrombosis through platelet activation induced by the release of cathepsin G, this novel property of heparin could be used to optimize its antithrombotic efficacy. PMID- 1425932 TI - Trans-ACPD induces a slow post-stimulus inward tail current (IADP) in guinea-pig olfactory cortex neurones in vitro. AB - The metabotropic glutamate receptor agonist trans-(+/-)-1-amino-1,3 cyclopentanedicarboxylic acid (trans-ACPD) produced a slow, persistent excitation of guinea-pig olfactory cortical neurones in vitro, and the appearance of a prominent post-stimulus after depolarization. The corresponding slow inward tail current (IADP) revealed under voltage clamp was insensitive to tetrodotoxin (or atropine) but was blocked by Cd2+ or tetrabutylammonium. The IADP properties resembled those of the slow inward tail current induced by muscarinic agonists in these neurones, suggesting a common intracellular transduction mechanism. PMID- 1425931 TI - 5-HT3 receptor antagonist effects of DAT-582, (R) enantiomer of AS-5370. AB - The serotonin 5-HT3 receptor antagonist effects of DAT-582, the (R) enantiomer of AS-5370 ((+/-)-N-[1-methyl-4-(3-methyl-benzyl)hexahydro-1H-1,4-diazepin-6- yl]-1H indazole-3-carboxamide dihydrochloride), and its antipode were compared with those of AS-5370 and existing 5-HT3 receptor antagonists. In anesthetized rats, DAT-582 antagonized 2-methyl-5-HT-induced bradycardia with an ED50 value of 0.25 microgram/kg i.v., whereas the (S) enantiomer was without effect even at 1000 micrograms/kg i.v. In antagonizing the bradycardia, DAT-582 was as potent as granisetron, slightly more potent than AS-5370, and 2, 5 and 18 times more potent than ondansetron, ICS 205-903 and renzapride, respectively, although it was less potent than zacopride. DAT-582 inhibited cisplatin (10 mg/kg i.v.)-induced emesis in ferrets with an ED50 value of 3.2 micrograms/kg i.v. twice. The antiemetic activity of DAT-582 was more potent than that of the existing 5-HT3 receptor antagonists examined, except zacopride. In contrast, the (S) enantiomer had little effect at 1000 micrograms/kg i.v. twice. In isolated guinea-pig ileum, DAT 582 inhibited 5-HT-induced contractions with an IC50 value of 91 nM, whereas the (S) enantiomer hardly inhibited them even at 1000 nM. These results suggest that DAT-582, the (R) enantiomer of AS-5370, potently and selectively blocks 5-HT3 receptors. PMID- 1425933 TI - Mediation of thyrotropin-releasing hormone induced gastric motility increases in developing rats. AB - Centrally administered thyrotropin-releasing hormone (TRH) induces vagally mediated gastrointestinal effects which may be cholinergic, serotonergic or a combination. This study investigated mediation of TRH-stimulated gastric motility in developing rats. A serotonin (5-HT) antagonist (5-HT2, ketanserin or xylamidine; 5-HT3, MDL 72222) or an acetylcholine receptor blocker (atropine) was administered intraperitoneally 30 min prior to intracisternal TRH (5-10 micrograms). The 5-HT-depleting para-chlorophenylalanine (p-CPA) was administered 48 or 72 h prior to TRH. Gastric motility, monitored via extraluminal strain gauge, was not increased with TRH in atropine-pretreated rats. MDL 72222 had a significant age-related effect on TRH-induced gastric motility increases while 5 HT2 antagonists and p-CPA treatment did not. Thus, acetylcholine receptor blockade inhibits TRH-stimulated gastric motility in young and adult rats while 5 HT3 antagonism eliminates the motility response in young (7 and 10 days) rats. PMID- 1425934 TI - Antinociceptive effects of Ca2+ channel blockers. AB - The antinociceptive action of four Ca2+ channel blockers, nifedipine, nimodipine, verapamil and diltiazem, was evaluated and compared to that of morphine using three algesiometric tests in mice and rats, namely, formalin, writhing and modified hot-plate test. Dose-response curves for all the drugs tested were similar and a significant dose-dependent antinociceptive action was evident in the formalin and writhing tests. However, in the hot-plate test, only nimodipine exhibited a significant analgesic effect, confirming the misleading results previously reported for this test. The findings suggest a pharmacological role of Ca2+ channel blockers in the modulation of antinociception under acute conditions. The analgesic action of Ca2+ channel blockers could be mediated by an increase in the nociceptive threshold resulting from interference with Ca2+ influx at opioid receptors, because Ca2+ influx is critical for the release of neurotransmitters and other substances implicated in nociception and inflammation. It is suggested that if a substance has a Ca2+ channel blocking effect, it should probably have some antinociceptive properties. PMID- 1425935 TI - Possible mechanism of immunosuppressive effect of scoparone (6,7 dimethoxycoumarin). AB - The possible mechanism of the immunosuppressive effect of scoparone (6,7 dimethoxycoumarin) was investigated. Human peripheral blood mononuclear cells (10(6) cells/ml) were stimulated with 0.25% phytohemagglutinin (PHA) and the proliferative response was determined from the uptake of tritiated thymidine. Scoparone (10(-6) to 3 x 10(-4) M) reduced the proliferative response in a dose dependent manner. The proliferative response of mononuclear cells to mixed lymphocyte reaction was also reduced by scoparone (10(-5) to 10(-4) M). Interleukin-1, interleukin-2 production and interleukin-2 receptor expression were all reduced in the presence of scoparone. Scoparone (10 and 30 microM) significantly reduced the suppression elicited by the diabetogenic drug, alloxan (10 mM). The suppressive activity of scoparone was significantly reduced by quinacrine (a phospholipase A2 inhibitor), indomethacin (a cyclooxygenase inhibitor) and nordihydroguaiaretic acid (a lipoxygenase inhibitor). The levels of prostaglandin E2, prostaglandin F2 alpha, leukotriene B4 and 2,3-dinor thromboxane B2 in culture medium of PHA-stimulated mononuclear cells, measured with an enzyme immunoassay, were elevated by scoparone treatment. We compared the effect of scoparone on the mononuclear cell response to genistein, a specific inhibitor of protein tyrosine kinase and demonstrated the non-additivity and cross-desensitization of the two compounds. Our results suggest that the immunosuppressive effect of scoparone may be exerted in part through inhibition of protein tyrosine kinase and release of arachidonic acid metabolites. PMID- 1425936 TI - 1,3-Di(2-[5-3H]tolyl)guanidine labels more than one site in rat forebrain. AB - Studies of 1,3-di-(2-[5-3H]tolyl)guanidine ([3H]DTG) binding to rat brain membranes revealed that [3H]DTG binds to a high and a low affinity site with Kd values of 19.8 nM and 1.31 microM (corresponding Bmax values 291 fmol/mg protein and 8.68 pmol/mg protein). The order of potency of competitors for [3H]DTG binding revealed a binding profile typical of sigma site ligands. Several sigma ligands such as the enantiomers of 3-PPP (3-(3-hydroxyphenyl)-N- (n propyl)piperidine) and (+/-)-pentazocine exhibited biphasic competition profiles for [3H]DTG binding, whereas other sigma ligands such as haloperidol displayed monotonic competition curves. Neither phenytoin nor carbamazepine were observed to enhance [3H]DTG binding. These data support the hypothesis that multiple sigma binding sites exist. The lack of phenytoin and carbamazepine modulation of [3H]DTG binding are in agreement with the proposed greater density of sigma site 2 in the rat, since allosteric modulation has been ascribed to the DM1/sigma 1 site. PMID- 1425937 TI - Discriminative stimulus effects of 8-OH-DPAT in pigeons: antagonism studies with the putative 5-HT1A receptor antagonists BMY 7378 and NAN-190. AB - Pigeons were trained to discriminate 0.3 mg/kg of the 5-HT1A receptor agonist 8 hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) from saline. RU 24969 (5-methoxy 3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole), at doses of 5.6-10 mg/kg, and eltoprazine (5.6 mg/kg), both mixed 5-HT1A/B agonists, substituted completely for 8-OH-DPAT, whereas 3.0-10 mg/kg of the 5-HT1B/C agonist TFMPP (1-(m trifluromethylphenyl)piperazine) and 0.1-3.0 of the 5-HT3 antagonist MDL 72222 (3 tropanyl-3,5-dichlorobenzoate) yielded only saline-appropriate responses. Substitution for 8-OH-DPAT by eltoprazine and RU 24969, which does not occur in rats, provides in vivo support for the suggestion that the absence of a 5-HT1B receptor in the pigeon allows more complete expression of 5-HT1A-mediated effects. BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)]8-azaspirol [4.5]- decane-7,9-dione) attenuated the 8-OH-DPAT stimulus at doses from 1.0 to 10 mg/kg but, when administered alone, also resulted in approximately 40% 8-OH DPAT-appropriate responding at the highest dose. NAN-190 (1-(2-methoxyphenyl)-4 [4-(2-phthalamido)butyl)-piperazine (0.3-3.0 mg/kg) produced a dose-dependent and complete antagonism of the 8-OH-DPAT-discriminative stimulus; administered alone NAN-190 resulted only in saline-key responding. NAN-190 also reversed the rate decreasing effects of higher doses of 8-OH-DPAT. The beta-adrenoceptor antagonist (+/-)-pindolol (5.6-17 mg/kg) antagonized the discriminative stimulus effects of lower 8-OH-DPAT doses but was unable to block the effects of higher doses of 8-OH DPAT. Prazosin (1.0-10 mg/kg), which like NAN-190, is an alpha 1-antagonist, neither substituted for nor blocked the discriminative stimulus effects of 8-OH DPAT. These results suggest that NAN-190 is an effective 5-HT1A receptor antagonist in this procedure with pigeons, with no indication of agonist actions, whereas BMY 7378 and pindolol are best characterized as partial 5-HT1A receptor agonists. PMID- 1425938 TI - Characterization and autoradiographic distribution of [3H]AF-DX 384 binding to putative muscarinic M2 receptors in the rat brain. AB - The novel radioligand [3H]AF-DX 384 binds specifically and saturably to putative muscarinic M2 receptor sites in homogenates of rat cerebral cortex. In saturation studies, [3H]AF-DX 384 appears to bind to two subpopulations of sites/states, one of high affinity (Kd1 = 0.28 +/- 0.08 nM) and another of low affinity (Kd2 = 28.0 +/- 5.0 nM). The maximal binding capacity (Bmax) of [3H]AF-DX 384 binding sites represented 9.7 +/- 2.3 fmol/mg protein (Bmax1) and 1993 +/- 551 fmol/mg protein (Bmax2) for the high and low affinity sites/states, respectively. The ligand selectivity profile of [3H]AF-DX 384 (at 2 nM) revealed that (-)-quinuclidinyl benzylate = atropine greater than 4-diphenylacetoxy-N-methylpiperidine methobromide greater than AQ-RA 741 greater than AF-DX 384 greater than UH-AH 371 much greater than methoctramine greater than oxotremorine-M greater than hexahydro-sila-defenidol much greater than pirenzepine greater than carbamylcholine much much greater than nicotine. This suggests that under our assay conditions [3H]AF-DX 384 binds mostly to M2-like muscarinic receptors in the rat central nervous system. This is further supported by the clear M2-like pattern of distribution observed using quantitative receptor autoradiography. High densities of specific labelling were seen in areas such as the hypoglossal nucleus, the pontine nucleus, the superior colliculus, the motor trigeminal nucleus, various thalamic nuclei and certain cortical laminae. Compared to [3H]AF DX 116, the percentage of specific binding detected with [3H]AF-DX 384 was much higher. This is likely to be related to the greater chemical stability and affinity of [3H]AF-EX 384. In addition, autoradiograms obtained with [3H]AF-DX 384 (2 nM) are of better quality with film exposure periods five shorter than those needed for [3H]AF-DX 116 (10 nM). Therefore, [3H]AF-DX 384 displays a good selectivity for muscarinic M2 sites and offers major advantages, including higher affinity and greater stability, over previously used ligands. PMID- 1425939 TI - Blockade of hyperalgesia and neurogenic oedema by topical application of nitroglycerin. AB - Surprisingly, a single topical application of a nitroglycerin (NTG) gel in humans has been shown to cause analgesia and to reduce oedema in thrombophlebitis. In the present investigation, we showed that the NTG gel reduces prostaglandin E2 induced hyperalgesia and blocks neurogenic inflammation induced in rat skin by antidromic electrical stimulation of the saphenous nerve. These results offer an explanation for the effects of topical application of NTG observed in thrombophlebitis, which may be common to other cutaneous pathologies. The data also support the development of nitrates the effects of which are restricted to the site of application. PMID- 1425940 TI - Neurotoxic effect of prenatal exposure to MPTP on the dopaminergic systems of the marmoset brain. AB - MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was incidentally administered to pregnant marmosets during the whole gestational period, except for the last 15 days before term. The infant monkeys were killed 5 months after birth, and dopamine and its metabolites were measured in the striatum and the nucleus accumbens. Prenatal exposure to MPTP produced a marked dopamine depletion in these brain regions of the offspring, showing that MPTP is able to cross the placental barrier in primates. PMID- 1425941 TI - Isoflurane anesthesia is stereoselective. AB - The anesthetic effects of the (+) and (-) isomers of isoflurane were determined in mice. Like the clinically important racemate, both isomers produced dose dependent increases in anesthetic sleep time. A statistically significant (P less than 0.005, ANOVA) difference in the potencies of these isomers ((+) greater than (-)) was observed. To our knowledge, this is the first demonstration of a stereospecific action of a volatile anesthetic in vivo. PMID- 1425942 TI - Influence of rhein anthrone and rhein on small intestine transit rate in rats: evidence of prostaglandin mediation. AB - The present study was undertaken to investigate the role of prostaglandins in the shortening of transit time observed after intraduodenal administration of rhein anthrone and rhein. After intraduodenal administration of rhein anthrone (0.5-10 mg/rat), a dose-dependent acceleration of small intestinal transit was observed. The effect for rhein (1-10 mg/rat) was far less pronounced. In the same test conditions, analysis of small intestinal tissue revealed a significant increase of prostaglandin E2 (PGE2), reaching its maximum value 30 min after administration of rhein anthrone. The increase in PGE2 found 30 min after administration of rhein was not significant. The effects provoked by rhein anthrone could be largely prevented by pretreatment of the animals with indomethacin (1-3 mg rat) or cortisol (10 mg/rat). It is concluded that prostaglandins play an important role in the acceleration of the transit provoked in rats by rhein anthrone. PMID- 1425943 TI - The developmental electrophysiologic effects of moricizine HCl on the canine cardiac Purkinje fiber. AB - Using standard microelectrode techniques, the developmental cellular electrophysiologic effects of moricizine HCl on adult and neonatal canine Purkinje fibers were studied. Steady state and rate-related changes in the transmembrane action potentials produced by moricizine HCl in both age groups were characterized and compared. Also, the rate of barium-induced abnormal automaticity before and after drug was also investigated in neonatal and adult Purkinje fibers. The major findings of this study are as follows. (1) The steady state and rate-related depressant effects of moricizine HCl on Vmax were similar in both age groups. (2) Moricizine HCl shortened APD90 in the adult fibers to a greater extent than in the neonate. (3) The concentration of moricizine HCl required to significantly reduce the rate of abnormal automaticity was less in the neonate than in the adult. The effect of moricizine HCl on APD90 of individual Purkinje fibers is influenced both by their control APD90 value as well as by maturational factors. It is less clear whether developmental differences in the effects of moricizine HCl on abnormal automaticity are solely a result of differences in control rates of abnormal automaticity between the two age groups. PMID- 1425944 TI - Effects of YM435, a novel dopamine D1 receptor agonist, on pancreatic exocrine secretion in anesthetized dogs. AB - The effects of YM435, a novel dopamine (DA) D1 receptor agonist, on pancreatic exocrine secretion were investigated in anesthetized dogs. Each drug was injected i.a. as a single bolus. Graded doses of YM435 (0.3-30 nmol) produced dose dependent increases in the rate of secretion of pancreatic juice, with a maximum effect at approximately 10 nmol, and with a high concentration of bicarbonate and low concentration of protein. SCH23390 (3-30 nmol), a selective D1 receptor antagonist, caused a progressive parallel shift to the right of the dose-response curve for YM435-stimulated pancreatic secretion without changing the maximum response. Schild analysis of the data indicated that the inhibitory constant (Ki) value was 2.9 nmol, and that SCH23390 inhibited YM435-stimulated pancreatic secretion in a competitive manner. Both DA (0.01-3 mumol) and SKF38393 (0.3-30 mumol), a selective D1 receptor agonist, also increased the secretory rate and bicarbonate concentration, and decreased the protein concentration to the same extent as YM435. These results suggest that YM435 is a potent stimulant of pancreatic exocrine secretion by acting on DA D1 receptors of the pancreas in dogs. PMID- 1425945 TI - Effect of kynurenate on functional deficits resulting from traumatic spinal cord injury. AB - The potential role of excitatory amino acid (EAA) receptors in spinal cord trauma was examined in a standardized rat model of contusive injury. EAA antagonists were administered in a split-dose protocol with half given 5 min prior to and the remainder 15 min after contusion produced at the T8 vertebral level. Hindlimb function was assessed using a battery of tests of reflex and more complex behaviors at 1 day after injury and weekly thereafter through 4-8 weeks. Functional deficits were compared for groups administered intravenous MK 801 (1 mg/kg), dextromethorphan (10 mg/kg) and kynurenate (300 mg/kg) or the vehicle, saline, alone. In addition, possible effect of the drugs themselves on hindlimb function were assessed in uninjured controls. None of the drugs produced more than transient effect on uninjured rats. In contused rats, only kynurenate produced significant reductions in functional deficits as compared to saline controls. Significant improvement of hindlimb function was also observed when the thoracic cord was locally perfused with kynurenate via intrathecal cannulas and when kynurenate was directly infused into the contusive injury site by stereotaxic microinjection. Using the latter route of administration, a dose dependent effect of kynurenate (100, 200 and 400 nmol) on the ability of contused rats to use their hindlimbs in locomotion was demonstrated. The highest dose also resulted in a significant reduction in overall functional deficits from 1 week through 1 month and at 2 months after injury. Our results support the hypothesis that EAA receptors at or near the injury site are involved in producing a proportion of the overall functional deficits stemming from traumatic injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425946 TI - Effects of semotiadil fumarate (SD-3211) on renal hemodynamics and function in dogs. AB - Studies were carried out to define the effect of semotiadil on renal hemodynamics, renal function and renin release in pentobarbital-anesthetized dogs. Intrarenal arterial infusion of semotiadil resulted in a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, urinary excretion of electrolytes and renin release. Semotiadil did not affect the linear relationship between osmolar clearance and the free water reabsorption rate, and increased the urinary excretion of sodium and calcium to the same extent. These results suggest that the main tubular site of action of semotiadil is the proximal tubule. Intrarenal infusion of a potent non-peptide angiotensin II antagonist, DuP753 (15 micrograms/kg per min), resulted in an increase in RBF, GFR, urine flow and UNaV. In spite of the blockade of the intrarenal renin angiotensin system(RAS) with DuP753, semotiadil caused almost the same effects as it did in the absence of DuP753. These results suggest that the renal effects of semotiadil are independent of the intrarenal RAS. PMID- 1425947 TI - The influence of changes in perfusion pressure and angiotensin II on the renal excretory responses to atrial natriuretic peptides. AB - The renal actions of atriopeptin III were examined in anaesthetised rats at differing perfusion pressures before and following blockade of the renin angiotensin system. At normal perfusion pressure 1000 ng kg-1 atriopeptin III caused reversible increases in glomerular filtration rate, of 20%, urine flow, absolute and fractional sodium excretions of 51-93%. Reduction of left renal perfusion pressure to 80 mm Hg decreased glomerular filtration rate by 30% and urine flow, absolute and fractional sodium excretions by 80% while atriopeptin III administration only minimally changed these variables. Concomitantly, right kidney perfusion pressure rose by 15 mm Hg which significantly increased fluid output, while the atriopeptin III induced diuresis and natriuresis were significantly larger. During infusion of captopril 900 micrograms kg-1 h-1 when pressures at the left and right kidneys had been reduced and elevated, respectively, atriopeptin III caused larger excretory responses in both kidneys which were greater than without captopril. These result suggested that the atriopeptin III mediated natriuresis and diuresis were directly proportional to perfusion pressure and attenuated by angiotensin II. PMID- 1425948 TI - Differences between vasorelaxant responses of the canine and human mesenteric arteries and veins to amrinone. AB - Amrinone induced similar degrees of relaxation in human mesenteric arteries and veins contracted with KCl, but exerted a more potent vasodilator effect in canine mesenteric veins than in arteries. Dibutyryl cAMP had a stronger effect on KCl induced contraction in canine mesenteric veins than in arteries. These results suggest that amrinone promotes a different vasodilating action in human and canine mesenteric vessels, possibly via different sensitivity to cAMP in each vascular smooth muscle. PMID- 1425949 TI - Autoradiographic evidence for the occlusion of rat brain dopamine D3 receptors in vivo. AB - [125I]Iodosulpride binding was studied in frontal rat brain sections by quantitative autoradiography. Using preincubated (= washed) sections, selective labelling and identification of dopamine D3 receptors was obtained using 0.2 nM [125I]iodosulpride in the presence of 100 nM domperidone for the occlusion of the D2 receptors. A high density of D3 receptors was noticed in the islands of Calleja. When preincubation of the sections was omitted, no D3 receptor labelling could be achieved, indicating tight binding to the receptor of an endogenous inhibitor. Such a tight receptor occupancy was not observed for the D2 receptor and various other neurotransmitter receptors. The occlusion of the D3 receptor could be prevented by tetrabenazine-induced monoamine depletion of the rats. It can be concluded, therefore, that D3 receptors are massively occupied by a monoamine, likely to be dopamine. This observation prompts the question to what extent dopamine D3 receptors can become occupied in vivo by systematically applied exogenous compounds. PMID- 1425950 TI - Antiulcer and gastric secretory activity of N-phthaloyl gamma-aminobutyric acid. AB - N-Phthaloyl gamma-aminobutyric acid, a new gamma-aminobutyric acid derivative synthesized in this laboratory, has been found to possess anticonvulsant, antinociceptive and antistress activities. Effects of this derivative on gastric lesions induced by aspirin and ethanol were studied in rats. N-Phthaloyl gamma aminobutyric acid significantly inhibited both aspirin and alcohol ulceration. The ED50 in each case being 76.34 and 43.65 mg/kg i.p. respectively. The volume of gastric acid secretion was diminished but gastric mucus secretion was significantly enhanced. The antiulcer effect was blocked by bicuculline and 3 mercaptopropionic acid. We conclude that (a) N-phthaloyl gamma-aminobutyric acid possesses antiulcer activity (b) the new derivative is probably a non-specific gamma-aminobutyric acid receptor agonist (c) the observed activity may be due to a mucoprotective action. PMID- 1425951 TI - O-acylated heparin derivatives with low anticoagulant activity decrease proliferation and increase alpha-smooth muscle actin expression in cultured arterial smooth muscle cells. AB - Selectively O-acylated derivatives of various glycosaminoglycans were prepared and tested in vitro for their anticoagulant activity and their antiproliferative effect on rat and rabbit smooth muscle cells. When O-acylation (butyrylation or hexanoylation) had been performed on periodate-depolymerized heparin fragments having very low anticoagulant activity, the antiproliferative potency was markedly increased (IC50 = 2 and 1 micrograms/ml respectively, versus 31 micrograms/ml for starting compound) without an increase in anticoagulant activity. The antiproliferative activity was related to the degree of acylation. The O-acylated derivatives of heparin fragments were also very active in reversing the de-differentiation of smooth muscle cell in culture, as estimated by the increase in the expression of alpha-smooth muscle actin and alpha-smooth muscle actin mRNA. PMID- 1425952 TI - Effects of oxodipine on isolated rabbit aorta and mesenteric resistance vessels. AB - The inhibitory effects of the dihydropyridine Ca2+ antagonist, oxodipine, on contractions and 45Ca2+ influx stimulated by noradrenaline (NA) and high K+ in rabbit aorta were compared to the same parameters measured in mesenteric resistance arteries. In aortic rings oxodipine, 10(-11)-10(-6) M, inhibited in a concentration-dependent manner the contractions induced by high K+ (IC50 = 9.0 +/ 4.0 x 10(-10) M) or by Ca2+ in high K+ solution (IC50 = 6.2 +/- 2.4 x 10(-9) M), while responses to NA were only slightly affected (IC50 greater than 10(-6) M). In mesenteric resistance vessels oxodipine inhibited the contractions induced by high K+ and NA but was more effective against NA- than high K(+)-induced contractions (IC50 = 5.2 +/- 3.1 x 10(-10) and 1.2 +/- 1.8 x 10(-8) M, respectively). The concentration-inhibition curves for high K(+)-induced contraction and 45Ca2+ influx in aorta were almost superimposable (I50 = 2.2 +/- 2.0 x 10(-9) M), whereas NA-induced contractions were inhibited less than 45Ca2+ influx (I50 = 8.2 +/- 2.6 x 10(-8) M). In mesenteric resistance vessels the curves for contraction and 45Ca2+ influx stimulated by high K+ and NA were also superimposable, but 45Ca2+ influx stimulated by NA was more sensitive to oxodipine than that stimulated by high K+ (I50 = 3.9 +/- 2.0 x 10(-10) and 2.2 +/ 1.2 x 10(-8) M, respectively). It is concluded that the effects of oxodipine can be attributed to its ability to inhibit Ca2+ entry through both potential- and receptor-operated pathways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425953 TI - Ca(2+)-dependent inhibition of Ca(2+)-independent contraction in uterine smooth muscle. AB - Uterine smooth muscle of the rat shows Ca(2+)-independent contraction in response to oxytocin in Ca(2+)-free medium. Micromolar Ca2+ inhibits this contraction. We now tested whether Ca2+ itself is the cause of this inhibition. The ratio of fura 2 fluorescence, the indicator of the intracellular level of Ca2+, was increased in parallel with the degree of inhibition by Ca2+. When inhibition was elicited by Ca2+, EGTA released the inhibition. Comparison of the dose-response curve for oxytocin in Ca(2+)-free solution and that in the medium with 1 microM Ca2+ showed that the inhibition by Ca2+ is non-competitive. EGTA chelation of the intracellular Ca2+ by loading of EGTA as its acetoxymethylester resulted in diminution of inhibition by Ca2+. EGTA suppressed the Ca(2+)-induced contraction but did not affect Ca(2+)-independent contraction. It is concluded that the inhibition is induced by intracellular Ca2+ itself. PMID- 1425954 TI - Endothelins inhibit serotonin-induced platelet aggregation via a mechanism involving protein kinase C. AB - Endothelins are a family of three peptides that act as local hormones released by the endothelium. They were found to inhibit rabbit and dog platelet aggregation in vivo, but no effect was observed in vitro. In order to investigate the possible interaction between endothelins and human platelet serotonin receptors, their effects on platelet aggregation induced by serotonin was studied. Endothelin-1, -2 and -3 had a dual action, on platelet aggregation and calcium mobilization induced by serotonin. When added at the same time as serotonin, endothelin potentiated the response to the amine. On the contrary, preincubation of platelet suspension with endothelin resulted in a concentration-dependent inhibition of the serotonin-mediated platelet response. Moreover, endothelin-1 inhibited serotonergic amplification of epinephrine-induced aggregation of platelets. We hypothesize that endothelins can bind to the platelet membrane and interact with serotonin receptors. The diverse effect of endothelins on serotonin induced aggregation and calcium mobilization may be due to stimulation of protein kinase C. PMID- 1425955 TI - Further characterization of the 5-hydroxytryptamine 5-HT1-like receptor mediating contraction of guinea-pig iliac artery. AB - We recently described a 5-hydroxytryptamine 5-HT1-like receptor mediating contraction in guinea-pig isolated iliac artery. The present study was aimed at characterizing this receptor with respect to the currently recognized 5-HT1 receptor subtypes (5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D). The potencies of 13 drugs tested as agonists correlated with their affinities for 5-HT1D binding sites only. The concentration-response curve for 5-carboxamidotryptamine (5-CT, a 5-HT1 like receptor agonist) was unaffected by propranolol (10 microM), which is reported to have affinity for 5-HT1A, 5-HT1B and 5-HT1C recognition sites. Yohimbine (3 microM) and metergoline (1 microM) antagonized 5-CT with pKB values of 6.15 and 6.96, respectively. These values are close to those found in a functional correlate of 5-HT1D sites in the same species, namely the presynaptic 5-HT autoreceptor in guinea-pig brain cortex. The overall results support the view that the receptor studied is of the 5-HT1D subtype. The receptor shares close similarities with other vascular 5-HT1-like receptors mediating contraction, for example the receptor present in dog saphenous vein. PMID- 1425956 TI - Selective chiral inhibition of Ca2+ entry promoted by bisbenzyltetrahydroisoquinolines in rat uterus. AB - The effects of diltiazem and six bisbenzyltetrahydroisoquinoline alkaloids (antioquine, 7-O-methylantioquine, dimethylantioquine, monterine, granjine and cordobimine) were studied in rat isolated uterus in order to clarify the mechanisms of their relaxant actions. All the compounds tested completely relaxed KCl-induced contractions and totally or partially inhibited oxytocin-induced rhythmic contractions. Only alkaloids with absolute configurations (1R,1'S or 1R,1'R) acted intracellularly, promoting relaxation of contractile responses induced by oxytocin in a Ca(2+)-free medium, as does papaverine. Alkaloids of the antioquine series (1S,1'R) selectively inhibited Ca2+ entry. The great rigidity of these structures and their stereoselective action make these alkaloids useful in studies of the conformational features of the Ca2+ channel. PMID- 1425957 TI - The angiotensin hexapeptide 3-8 fragment potently inhibits [125I]angiotensin II binding to non-AT1 or -AT2 recognition sites in bovine adrenal cortex. AB - In the present studies, ligand competition experiments were conducted to examine the ability of angiotensin II peptide agonists and nonpeptide AT1- and AT2 selective receptor antagonists to inhibit the binding of [125I]angiotensin II to bovine adrenal cortical membranes. Angiotensin II, angiotensin III, the All-(3-8) hexapeptide fragment of angiotensin II, and the AT1-selective receptor antagonist L-158,809, inhibited [125I]angiotensin II binding in a biphasic fashion indicative of a ligand interaction at more than one recognition site. Approximately 20% of low affinity [125I]angiotensin II binding was inhibited only by high micromolar concentrations of L-158,809. RG 13647 (1(-1,4-benzodioxan-2 methyl)-5-diphenylacetyl-4,5,6,7-tetra hydro-1H-imidazo- [4,5,c]-pyridine-6 carboxylic acid) represents a potent and AT2-selective analog of PD 123177 and showed weak activity in competing for [125I]angiotensin II binding with an IC50 value of 100 microM. When subsequent competition studies were conducted in the presence of 1 microM L-158,809 to block [125I]angiotensin II to the AT1 receptor subtype, the angiotensin II agonists produced monophasic inhibition curves with AII-(3-8) showing the greatest activity (IC50 = 6 nM) followed by angiotensin III (IC50 = 15 nM) much greater than angiotensin II (IC50 = 110 nM). RG 13647 was not found to significantly inhibit this portion of [125I]angiotensin II binding. These data demonstrate that bovine adrenal cortex contains both the AT1 receptor subtype, as well as, a novel class of [125I]angiotensin II recognition sites which may be analogous to the recently described angiotensin IV (AT4) receptor. PMID- 1425958 TI - JMV 449: a pseudopeptide analogue of neurotensin-(8-13) with highly potent and long-lasting hypothermic and analgesic effects in the mouse. AB - We recently reported that H-Lys psi (CH2NH)Lys-Pro-Tyr-Ile-Leu-OH (JMV 449), a pseudopeptide analogue of neurotensin-(8-13) with a reduced CH2NH bond in position 8-9, was about 3 times more potent than neurotensin in binding to mouse brain membranes and in contracting the guinea-pig ileum, and was markedly more resistant to degradation than neurotensin when exposed to rat brain membranes. In the present study, we compared the time courses and dose-response relationships for the ability of i.c.v. injected neurotensin and JMV 449 to elicit hypothermia and analgesia (tail-flick test) in the mouse. The results show that the pseudopeptide analogue behaved as a highly potent and long-lasting neurotensin agonist in these two in vivo bioassays. The analogue should prove very useful for studying the effects of chronic neurotensin receptor stimulation in vitro and in vivo. PMID- 1425959 TI - Effect of LY 83583 on relaxation induced by non-adrenergic non-cholinergic nerve stimulation and exogenous nitric oxide in the rat gastric fundus. AB - In the rat gastric fundus, the reported cGMP-lowering agent LY 83583 (10(-5) M) inhibited the relaxation induced by nitric oxide (NO), without altering the response to isoprenaline, vasoactive intestinal polypeptide, sodium nitroprusside or electrical field stimulation of inhibitory non-adrenergic non-cholinergic neurones, which are thought to release NO. Incubation with superoxide dismutase partially prevented the effect of LY 83583. When added during a relaxation maintained by continuous NO infusion, LY 83583 reversed the relaxation. It is concluded that LY 83583 inactivates exogenous NO through the generation of superoxide anions. PMID- 1425960 TI - Tissue-specific localization of mitochondrial imidazoline-guanidinium receptive sites. AB - In the present report, we studied the distribution of the imidazoline-guanidinium receptive site in mitochondrial fractions from different rabbit and human tissues. Binding studies of the imidazoline-guanidinium receptive site ligand [3H]idazoxan, allowed to distinguish two groups of tissues: the first one, including kidney, brain and liver, displays a high density of imidazoline guanidinium receptive site; the second one, consisting of striated and smooth muscle, enterocytes, lung, spleen and heart, is characterized by 4- to 16-fold lower binding site density. The demonstration that mitochondrial imidazoline guanidinium receptive sites are not equally expressed in all tissues can be considered as a further progress towards the characterization of their functional activity. PMID- 1425961 TI - Endothelin-1 enhances vascular permeability in the rat heart through the ETA receptor. AB - Intravenous injection of endothelin-1 (ET-1, 0.1 and 1 nmol/kg) resulted in a dose-dependent increase in vascular permeability in the coronary circulation of conscious rats. The increase was almost completely abolished by the selective ETA receptor antagonist, BQ-123 (1 mg/kg). The ET-1 analogue, [Trp(For)21]ET-1, which is devoid of the depressor but not the pressor activity, evoked changes in protein extravasation similar to those with ET-1. These data indicate that the permeability effect of ET-1 is mediated through the ETA receptor. PMID- 1425962 TI - Cocaine place preference is blocked by the delta-opioid receptor antagonist, naltrindole. AB - Naltrindole, a selective delta-opioid receptor antagonist, was evaluated for its potential to block the reinforcing properties of cocaine using a conditioned place pairing paradigm in Lewis rats. Cocaine HCl (15 mg/kg s.c.) produced a strong place preference which was significantly blocked in animals pretreated with naltrindole (3 mg/kg i.p.); naltrindole alone showed no reinforcing or aversive effects. The results suggest a novel approach for the treatment of cocaine abuse in man. PMID- 1425963 TI - Cross tolerance between cromakalim and RP49356 in the uterus of the rat in vivo and in vitro. AB - We investigated tolerance to the potassium (K+) channel openers, cromakalim and RP49356 and cross tolerance between them in the uterus of the rat. Continuous infusion of RP49356 in vivo produced 5.2-fold (200 or 300 micrograms/kg per h) and 7.2-fold (600 micrograms/kg per h) desensitization of the uterus to RP49356. Uterine sensitivity to RP49356 was reduced 7.4-fold in cromakalim-tolerant rats and sensitivity to cromakalim was reduced 7.9-fold in RP49356-tolerant rats. Incubation of isolated uterus with 10 microM cromakalim for 4 h reduced uterine sensitivity to cromakalim by about 45-fold and to RP49356 by 2.1-fold but did not alter sensitivity to salbutamol. Incubation with 10 microM RP49356 for 4 h reduced sensitivity to RP49356 by 2.5-fold and to cromakalim by 3.8-fold. Occurrence of uterine tolerance to K+ channel openers in vitro suggests that tolerance in vivo has a pharmacodynamic basis. Cross tolerance between cromakalim and RP49356 provides evidence that these two K+ channel openers possess common binding sites and/or mechanism(s) of action. However, the greater extent of self tolerance to cromakalim than to RP49356 suggests a difference in their actions. PMID- 1425964 TI - Intestinal relaxation by endothelin isopeptides: involvement of Ca(2+)-activated K+ channels. AB - Our previous studies have shown that endothelin-1 (ET-1) induces an initial relaxation followed by a contraction in the guinea-pig ileum. To test whether other ET isopeptides (ET-2, ET-3, vasoactive intestinal contractor (VIC) and sarafotoxin S6b) and big ET-1, the ET-1 precursor, also induce similar biphasic responses, we compared their effects in isolated guinea-pig ileum. In addition, the mechanism of initial relaxation was studied. At 1-100 nM, ET-1, ET-2 and VIC were equipotent in producing the biphasic responses. S6b also produced similar biphasic responses, except that only a relaxation was elicited at 1 nM. ET-3 was approximately 30- to 100-fold less active than ET-1 in producing the contraction, whereas it was as potent as ET-1 in producing relaxation. Big ET-1 induced a relaxation of slower onset and longer duration, followed by a weak contraction at concentrations higher than 30 nM. The initial relaxation produced by ET-1 was not affected by pretreatment with L-NAME (NW-nitro-L-arginine methyl ester), hemoglobin, 9-AC (anthracene-9-carboxylic acid), SITS (4-acetamido-4' isothiocyanatostilbene-2-2'-disulfonic acid), glibenclamide, ouabain, phorbol 12,13-dibutyrate, sodium nitroprusside, human atrial natriuretic peptide (hANP) or forskolin, whereas it was abolished by pretreatment with apamin. Although phorbol 12,13-dibutyrate pretreatment had no significant effect on the biphasic response of ET-1, it rapidly reversed the sustained contraction produced by ET-1. These results indicate that the initial relaxation is caused by the activation of Ca(2+)-activated K+ channels. PMID- 1425965 TI - Effects of chronic treatment with caffeine on kidney responses to angiotensin II. AB - Previous studies demonstrate that chronic administration of caffeine causes glomerular filtration to deteriorate in rats with high-renin renovascular hypertension. A partial explanation for these findings could be that chronic administration of caffeine alters the effects of angiotensin II on the kidney. As an initial test of this hypothesis, we compared the acute effects of intrarenal infusions of angiotensin II (3 ng/min) on renal function in control rats versus rats treated with 0.1% caffeine in their drinking water for 1 week. The renal responses to angiotensin II in a group of animals receiving acute intrarenal infusions of adenosine (10 micrograms/min) were also measured to determine whether caffeine and adenosine modulated renal responses to angiotensin II in opposite directions. All studies were performed in the in situ blood perfused rat kidney. Neither caffeine nor adenosine significantly altered angiotensin II induced changes in renal blood flow, urinary excretory function or renin release. However, caffeine augmented and adenosine attenuated the increase in filtration fraction caused by angiotensin II. The fact that caffeine potentiates angiotensin II-induced increases in filtration fraction without affecting angiotensin II induced reductions in renal blood flow is consistent with, but does not prove, the hypothesis that chronic administration of caffeine modifies the effects of angiotensin II on the renal microvasculature. If this inference is correct, caffeine could facilitate renal damage in high-renin hypertension by exacerbating angiotensin II-induced increases in glomerular capillary hydrostatic pressure. PMID- 1425966 TI - Blood pH and the actions of nifedipine on cardiac excitation-contraction coupling. AB - Hearts from male Sprague-Dawley rats were perfused, by the Lagendorff method, with calcium-free Krebs solution (containing either adrenaline or a high level of potassium) at pH 7.48 (control), 7.26 (acidosis) or 7.69 (alkalosis). When the hearts stopped contracting, a dose of nifedipine or its vehicle was given before measuring the force of contraction, coronary perfusion pressure and heart rate in response to graded doses of calcium. The calcium-antagonising efficacy of nifedipine was reduced during acidosis in both adrenaline- and potassium stimulated hearts, but the reduction was greater in the adrenaline-stimulated hearts. Alkalosis led to a small increase in the efficacy of nifedipine on adrenaline- and potassium-stimulated contractions. PMID- 1425967 TI - Na+,2Cl-,K+ cotransport system as a marker of antihypertensive activity of new torasemide derivatives. AB - A series of compounds related to torasemide, a loop diuretic, were synthesized and examined for their diuretic potency and inhibitory activity on the erythrocyte and renal medullary thick ascending limb vesicle Na+,2Cl-,K+ cotransport in Milan hypertensive (MHS) and normotensive (MNS) rat strains, where previous studies had demonstrated an alteration of the cotransport system genetically related to hypertension. From the results of the screening, structure activity relationships were drawn and two compounds, JDL 961 and C 2921 were selected. Their IC50 on renal vesicle cotransport were similar in the two strains (JDL 961: MHS = 1.8 microM; MNS = 1.2 microM; C 2921: MHS = 4 microM; MNS = 3.8 microM), and were 4-8 times lower than those of torasemide (MHS = 13 microM; MNS = 31 microM, P less than 0.01) and 50-60 times lower than those of bumetanide (MHS = 145 microM; MNS = 206 microM, P less than 0.05) taken as reference compounds. Their ability to reduce the development rate of hypertension was tested both in MHS and in Okamoto spontaneously hypertensive rats (SHR) strain, in which cotransport alterations are opposite to those of MHS. Both torasemide derivatives (7.5 mg.kg-1 os per day) prevented development of hypertension in the two strains. The time course of this hypotensive activity was faster and the percentage of blood pressure fall greater in MHS (20-25%) than in SHR rats (12 15%), even though the absolute value of blood pressure fall was similar in MHS (JDL 961 = -17 mm Hg; C 2921 = -30 mm Hg) and SHR (JDL 961 = -25 mm Hg; C 2921 = 20 mm Hg). A superimposable effect of bumetanide was observed in the two strains, but at 8 times higher daily dose (60 mg.kg-1). These results suggest that new loop diuretics can be selected for their antihypertensive activity on the basis of their in vitro potency in inhibiting the Na+,2Cl-,K+. PMID- 1425968 TI - Different utilization of Ca2+ in the contractile action of endothelin-1 on cerebral, coronary and mesenteric arteries of the dog. AB - Vasoconstrictor responses to endothelin-1 (ET) were compared between endothelium denuded strips of cerebral, coronary and mesenteric arteries of the dog. Contractile responses to lower concentrations (below 3 x 10(-10) M) of ET were significantly greater in the cerebral and coronary arteries than in the mesenteric artery. The cerebral and coronary arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a 0-Ca solution. Readdition of Ca2+ to the cerebral and coronary arteries placed in the 0-Ca solution caused a biphasic contraction which was susceptible to inhibition by nifedipine. When ET below 10(-10) M was introduced before the Ca2+ contraction, this peptide produced no detectable contraction, but augmented the Ca2+ contraction. The augmented Ca2+ contractions were abolished by 10(-7) M nifedipine. These effects of ET were not observed in the mesenteric artery. The contractile responses of the mesenteric artery to ET determined in the presence of elevated extracellular K+ concentrations were comparable to the responses of the cerebral artery to this peptide determined in the presence of normal K+ concentrations. These results indicate that the enhanced responses to ET in the cerebral and coronary arteries were dependent on the Ca2+ influx through voltage dependent Ca2+ channels and suggest that these channels are in an activated state when these arteries are in a resting state. PMID- 1425970 TI - The spinal and peripheral roles of bradykinin and prostaglandins in nociceptive processing in the rat. AB - The effect of peripheral and intrathecal administration of the bradykinin B2 receptor antagonist HOE140 and the non-steroidal anti-inflammatory drug indomethacin were studied on the response of dorsal horn nociceptive neurones to formalin in the anaesthetized rat. Peripheral pretreatment with HOE140 reduced both phases of the formalin response whereas subcutaneous administration of indomethacin (5 mg/kg) reduced only the second phase. Pre-treatment with intrathecal HOE140 resulted in a dose-dependent reduction of the second phase whereas a high dose (500 micrograms) intrathecal indomethacin reduced both phases of the response. Bradykinin plays a role in peripheral nociception during the first and second phase of the response whereas the prostaglandins are only involved during the second phase. The converse is true centrally, the prostaglandins appear to be involved in both phases of the formalin response whereas bradykinin only plays a central role during the second phase of the response. PMID- 1425969 TI - Antihypertensive and vasodilator effect of A-80b, a new pyridazino indole derivative. AB - The hypotensive and antihypertensive activities of a A-80b, a newly synthesized pyridazino[4,5-b]indole derivate were investigated in anaesthetized rats. In vitro studies were also done to examine the possible mechanism of its vasodilator action. A 80b (3-15 mg/kg i.p.) showed potent and long-lasting antihypertensive activity in spontaneous hypertensive rats. In normotensive rats, A-80b (7.5-30 mg/kg i.p.) also lowered blood pressure but less than in hypertensive rats. The decrease in diastolic pressure was greater than the decrease in systolic pressure and cardiac frequency was not modified significantly. Contractile responses induced in isolated rat thoracic aorta by K+ and noradrenaline were inhibited by A-80b. In K(+)-depolarized rat aorta, A-80b showed dose-dependent inhibition of the Ca(2+)-induced contraction. Also, A-80b inhibited spontaneous contractions of rat portal vein. The vasodilator action seemed to be endothelium-independent. These results suggest that A-80b is a new chemical entity which exerts a hypotensive and antihypertensive effect, possibly attributable to vasodilator activity via interference with Ca2+ influx and probably Ca2+ mobilization from intracellular stores. PMID- 1425971 TI - Memantine prevents quinolinic acid-induced hippocampal damage. AB - Memantine, used as a drug for treatment of spasticity and other extrapyramidal disorders as well as dementia, was shown to prevent brain damage caused by the glutamate (N-methyl-D-aspartate, NMDA) receptor agonist, quinolinic acid. Studies were focused on the hippocampal formation which is known to be highly vulnerable to quinolinate. Pretreatment of animals with memantine added to the food led to a reliable protection of hippocampal neurons when the drug was administered chronically for a period of 10 days prior to quinolinate exposure (i.c.v. injected). Additional i.p. administration of memantine (simultaneously with quinolinic acid or up to 24 h later) did not substantially add to the protective potency of the memantine diet. Our findings indicate that memantine may have beneficial effects in the treatment of brain disorders which are mediated by excitotoxic effects of glutamate. PMID- 1425972 TI - Heterogeneity of contractile 5-HT receptors in human hand veins. AB - To increase our knowledge of human peripheral vasospasm we characterized the contractile 5-hydroxytryptamine (5-HT) receptors in human superficial hand vein segments in vitro. The 5-HT1 receptor agonist, sumatriptan, the 5-HT2 receptor agonist, dl-alpha-methyl-5-HT, and the 5-HT3 receptor agonist, 2-methyl-5-HT, all induced concentration-dependent contractions. The contractile response to sumatriptan was antagonized by the non-selective 5-HT receptor antagonist, methiothepin, but was unaffected by the 5-HT2 receptor antagonist, ketanserin. The contractile response to dl-alpha-methyl-5-HT was antagonized by both methiothepin and ketanserin. The contraction elicited by 2-methyl-5-HT was not affected by the 5-HT3 receptor antagonist, MDL 72222, but was antagonized by ketanserin. The results suggest that serotonergic contraction in the human superficial hand vein involves both 5-HT1 and 5-HT2 but not 5-HT3 receptors. Such receptor heterogeneity in human blood vessels should be considered when using drugs and when designing future compounds for medical use. PMID- 1425974 TI - Olvanil: more potent than capsaicin at stimulating the efferent function of sensory nerves. AB - The capsaicin analogue olvanil stimulated an increase in cutaneous blood flow when injected intradermally into the anaesthetised rabbit, as measured using a 133Xenon clearance method. Olvanil was found to be a 10-fold more potent vasodilator (on a molar basis) than capsaicin. The effect of both vasodilators was significantly inhibited by the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37). These findings suggest that olvanil stimulates the efferent function of cutaneous sensory nerves in a more potent manner than capsaicin. We therefore suggest that olvanil is a useful pharmacological tool for studying the activity of neuropeptides released from sensory nerves. PMID- 1425973 TI - Pregnenolone sulfate increases the convulsant potency of N-methyl-D-aspartate in mice. AB - The neurosteroid pregnenolone sulfate is known to specifically enhance NMDA-gated currents in spinal cord neurons. The response does not appear to be mediated by the glycine/NMDA modulatory site. Here we found that pregnenolone sulfate significantly increased the convulsant potency of N-methyl-D-aspartate (NMDA), but not of pentylenetetrazol (PTZ). In agreement with previous in vitro reports showing that the glutamergic NMDA receptor is also specifically modulated by steroids, our findings suggest that pregnenolone sulfate selectively activates the NMDA receptors involved in convulsions in the intact animal. PMID- 1425975 TI - AF102B, a muscarinic M1 receptor agonist, mimics some effects of acetylcholine on neurons of rat hippocampus slices. AB - The putative muscarinic M1 receptor agonist, AF102B, was applied to rat hippocampal slices and the responses of intracellularly recorded pyramidal cells were examined. AF102B mimicked some effects of acetylcholine on these cells as follows: at low concentration, AF102B attenuated a slow after-hyperpolarization in response to a long depolarizing current pulse. This effect was blocked by the M1 antagonist, pirenzepine. At higher concentrations, AF102B also depolarized the cells and caused an increase in their input resistance. AF102B did not affect local excitatory postsynaptic potentials or reactivity to topically applied excitatory amino acid substances. These experiments indicate that AF102B acts as an agonist at some muscarinic M1 receptor subtypes in mammalian brain. PMID- 1425976 TI - The selective protein kinase C inhibitor, NPC 15437, induces specific deficits in memory retention in mice. AB - We studied the effects of a selective inhibitor of protein kinase C (PKC), 2,6 diamino-N-[(1-(1-oxotridecyl)-2-piperidinyl]methyl)hexamide (NPC 15437), on acquisition and memory retention of a Y-maze avoidance task in mice. Post training administration of NPC 15437 (0.1-10 mg/kg i.p.) induced a dose-dependent deficit in retention of the temporal but not the spatial component of the task. This selective amnesia does not reflect state dependence and NPC 15437 (1 mg/kg) had no effect on acquisition and memory retrieval. Our results suggest that this new PKC inhibitor interferes with mechanisms underlying memory consolidation. This is in agreement with recent findings suggesting that PKC is involved in memory processes. PMID- 1425977 TI - Direct vascular actions of hydrochlorothiazide and indapamide in isolated small vessels. AB - The mechanism by which thiazides lower peripheral resistance is unresolved. The aim of this study was to investigate the mechanisms of the acute vasodilator action of hydrochlorothiazide and the 'thiazide-like' diuretic indapamide on human, guinea pig and rat small arteries. Vessels were mounted on a myograph and the relaxation profile of both drugs and interactions with K+ channels and the vascular eicosanoid system were studied. Neither drug had any relaxant effect in rat mesenteric vessels and indapamide did not relax human arteries. Hydrochlorothiazide in both human and guinea pig vessels produced significantly more relaxation of noradrenaline than K(+)-constricted vessels (P less than 0.001). Relaxation to hydrochlorothiazide was reduced in the presence of charybdotoxin. Maximal-induced hydrochlorothiazide relaxation was reduced by 64% in human arteries (P less than 0.001) and by 91% in guinea pig vessels (P less than 0.001). Incubation with glibenclamide and indomethacin had no effect on the relaxant activity of hydrochlorothiazide and indapamide. Indapamide-induced relaxation was unaffected in the presence of charybdotoxin. These results show marked differences in the acute vasodilator action of hydrochlorothiazide and indapamide. There appears to be involvement of Ca(2+)-activated K+ channels in the acute vasorelaxant activity of hydrochlorothiazide. PMID- 1425978 TI - 5-Hydroxydecanoate inhibits ATP-sensitive K+ channel currents in guinea-pig single ventricular myocytes. AB - We investigated the effect of 5-hydroxydecanoate, a novel antiarrhythmic agent, on the electrical activity of guinea-pig ventricular myocytes. The outward K+ current increased by lowering the intracellular ATP concentration (0.5 mM) was efficiently blocked by 5-hydroxydecanoate when recording in the whole cell configuration with the application of voltage ramps. The increase in the time independent outward K+ current induced by reducing intracellular ATP to 0 mM was also blocked by 5-hydroxydecanoate (10 or 100 microM) and by tolbutamide (1 mM). Using the single channel recording technique, we found that 5-hydroxydecanoate blocked ATP-sensitive K+ channels when its channel open probability was increased by 1 mM ATP together with 1 mM ADP or by an intracellular pH of 6.6. These conditions are well documented to reflect metabolic changes in the early stages of myocardial ischemic attack. These results suggest that 5-hydroxydecanoate could inhibit ATP-sensitive K+ channels, resulting in an antiarrhythmic effect specifically on ischemic hearts. PMID- 1425979 TI - Prostanoid-mediated vascular contraction in normotensive and hypertensive rats. AB - We investigated the role of prostanoids in the constrictor effect of calcium ionophore A23187, endothelin-1 and vasopressin in rings of thoracic aorta obtained from normotensive rats and rats with aortic coarctation-induced hypertension. Isometric tension was measured in aortic rings bathed in buffer with and without indomethacin (10 microM), CGS13080 (10 microM) or SQ29548 (1 microM) to inhibit cyclooxygenase and thromboxane synthase and to block TxA2-PGH2 receptors, respectively. Increases in tension elicited by A23187 and vasopressin in aortic rings from hypertensive rats exceeded responses in rings from normotensive rats. A23187-induced contractions were virtually abolished by indomethacin and SQ29548, and slightly attenuated by CGS13080. These agents also attenuated the contractions elicited by endothelin but not by vasopressin. According to these data, a prostanoid(s) agonist for TxA2-PGH2 receptors contributes to the constrictor effect of A23187 in aortic rings of hypertensive rats, and of endothelin in aortic rings of normotensive and hypertensive rats. Moreover, the expression of prostanoid-mediated contractions as it pertains to the aortic response to A23187 is greatly increased in hypertensive rats. PMID- 1425980 TI - Homologous tachyphylaxis to bradykinin and its interference with allergic pleurisy in actively sensitized rats. AB - After recovery from a first intraplantar or intrathoracic stimulation with bradykinin, repeated daily provocation with this peptide resulted in a progressive loss of its ability to cause paw or pleural oedema, reaching 0-20% of the control within seven and four consecutive provocations, respectively. The phenomenon was shown to be time reversible, since the unresponsiveness ceased when stimulations were discontinued, and localized, since paw oedema evoked by the peptide was not modified after desensitization of either the contralateral paw or the pleural cavity. Furthermore desensitization to bradykinin did not influence the pleurisy elicited by either histamine (200 micrograms/cavity), 5 hydroxytryptamine (5-HT) (100 microgram/cavity) or platelet-activating factor (PAF) (1 microgram/cavity), suggesting that the desensitization was selective. In contrast, when actively sensitized animals were submitted to bradykinin-induced tachyphylaxis, pleural exudation and leukocyte influx induced by antigen were drastically reduced, strongly implying bradykinin in this process. We demonstrated that repeated daily stimulation with bradykinin cause selective, local and reversible auto-refractoriness, which may be useful as a tool in attempting to evaluate the role of this peptide in inflammation. PMID- 1425981 TI - Doxorubicin: an antagonist of muscarinic receptors in guinea pig heart. AB - While studying the mechanisms of doxorubicin-induced cardiotoxicity, we observed that doxorubicin inhibited the negative inotropic effect of acetylcholine in isolated heart muscle preparations. We therefore examined the effects of doxorubicin on muscarinic acetylcholine receptors. In left atrial muscle preparations isolated from guinea pig heart and stimulated at 2 Hz at 30 degrees C, doxorubicin caused a parallel right-ward shift of the dose-response curves for the negative inotropic effects of acetylcholine. The inhibitory action was reversed by an additional incubation in the absence of doxorubicin. Doxorubicin reversed the carbachol-induced inhibition of developed tension: a high concentration of doxorubicin brought the force back to its original strength. Doxorubicin inhibited specific [3H]quinuclidinyl benzilate (QNB) binding to membrane preparations obtained from ventricular muscle of guinea pig hearts. The pA2 value for doxorubicin obtained in the inotropic study corresponded to the IC50 value for doxorubicin observed in the [3H]QNB binding assay. These results indicate that doxorubicin acts as a weak competitive antagonist on muscarinic acetylcholine receptors. PMID- 1425982 TI - Cardiovascular effects of the new nitric oxide donor, pirsidomine. Hemodynamic profile and tolerance studies in anesthetized and conscious dogs. AB - The hemodynamic profile of pirsidomine, a new donor of NO (nitric oxide), was evaluated in dogs. In anesthetized dogs, the intravenous or intraduodenal administration of pirsidomine (0.3-10 mg/kg) decreased dose relatedly the preload and afterload of the heart, total peripheral resistance, cardiac output, left ventricular work and myocardial oxygen consumption. In conscious renal hypertensive dogs, oral administration of pirsidomine (1.0-10 mg/kg) caused a marked and sustained decrease in systolic blood pressure and left ventricular end diastolic pressure, which was accompanied by a slight and transient increase in heart rate and contractility. The diastolic blood pressure was affected less than in anesthetized dogs. Similar hemodynamic effects were obtained with M1 (3-(1 (2,6-dimethylpiperidino))-sydnonimine; 0.3-1 mg/kg), the main metabolite of pirsidomine, and with the known NO donor, isosorbide-5-mononitrate (IS-5-MN; 2-10 mg/kg). Tolerance development after repeated administration of pirsidomine and IS 5-MN was also investigated. In anesthetized dogs, repeated intraduodenal administrations of pirsidomine did not attenuate the response whereas tolerance occurred with hemodynamically equieffective doses of IS-5-MN. In conscious dogs, long term oral treatment, three times daily every 8th h for 5 days, revealed tolerance to IS-5-MN, slight or no tolerance to pirsidomine, and no cross tolerance between the two agents. The results indicate that pirsidomine possesses an antianginal hemodynamic profile similar to that of its main metabolite, M1, and of IS-5-MN. This suggests a common mode of action via the release of NO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1425983 TI - Effects of angiotensin II and angiotensin III on airway epithelial short-circuit current: involvement of pertussis toxin-sensitive G protein. AB - The effects of angiotensin II (AII) and angiotensin III (AIII) on bioelectric properties of canine cultured tracheal epithelium were investigated. Both peptides increased the short-circuit current (Isc), an effect that was accompanied by the release of prostaglandin (PG) E2 and was abolished by indomethacin and diphenylamine-2-carboxylate but not by amiloride. The AII action was not altered by amastatin. The increases in Isc induced by AII and AIII were inhibited by pertussis toxin, whereas cholera toxin had no effect. Thus, both peptides may selectively stimulate airway epithelial Cl- secretion through the activation of pertussis toxin-sensitive regulatory G protein and the subsequent generation of PGE2. PMID- 1425984 TI - Increase of serotonin in plasma during onset of halothane-induced malignant hyperthermia in pigs. AB - The levels of serotonin (5-HT) were determined in platelet-free and platelet-rich plasma before and during the onset of halothane-induced malignant hyperthermia (MH) in genetically MH-susceptible pigs. During MH onset, the free (i.e. physiologically active) levels of 5-HT in plasma rose concomitantly with the increases in muscle tone, body temperature, venous pCO2 and plasma lactate. Since pharmacological stimulation of 5-HT2 receptors has recently been shown to trigger MH in susceptible pigs, the finding of increased 5-HT plasma levels during onset of halothane-induced MH may indicate that 5-HT is involved in the mechanisms by which volatile anesthetics trigger this myopathic syndrome. PMID- 1425985 TI - Prejunctional modulation of sensory-motor nerve mediated vasodilation of the rat mesenteric arterial bed by adenosine. AB - The effect of adenosine on the vasodilator response of the rat mesenteric arterial bed to electrical field stimulation of perivascular sensory-motor nerves was examined. Adenosine (0.3-10 microM) produced a concentration-dependent attenuation of the vasodilator response to electrical stimulation of sensory motor nerves, which is mediated by the sensory neuropeptide calcitonin gene related peptide (CGRP). The adenosine receptor antagonist, 8-phenyltheophylline (1 microM) competitively antagonized the inhibitory effect of adenosine. Adenosine did not affect the vasodilator response to exogenous CGRP, thus indicating that the inhibitory action of adenosine on the vasodilator response to perivascular sensory-motor nerve stimulation was prejunctional. PMID- 1425986 TI - Ca(2+)-independent contraction of uterine smooth muscle induced by vanadate and its inhibition by Ca2+. AB - Vanadate, 30 microM, contracts uterine smooth muscle of estrogen-dominated non pregnant rats in Ca(2+)-free medium after preincubation with 3 mM EGTA. In spite of the phosphorylation of the myosin light chain during this contraction, studies with fura-2 suggested that this contraction was not accompanied by an increase in the cytosolic Ca2+ level. Inhibitors of the myosin light chain kinase and protein kinase C partly inhibited this contraction. Vanadate seems to enter the cell through anion channels to inhibit phosphatases, resulting in phosphorylation via basal activities of the myosin light chain kinase and protein kinase C. An increase in the cytosolic free Ca2+ level resulted in relaxation of the contracting muscle in the same manner as in the oxytocin-induced Ca(2+)-free contraction. PMID- 1425987 TI - Kinetics of relaxation responses to vasorelaxants in isolated rabbit aorta. AB - Transient responses of isolated tissues to drugs are best studied by application of non-steady-state protocols in which the data collected are analyzed using kinetic models. The time dependence of the relaxation response of the adventitia- and endothelium-denuded rabbit aorta to four vasorelaxants (nitroglycerin, sodium nitroprusside, 5'-N-ethylcarboxamidoadenosine and isoproterenol) was analyzed by an exploratory kinetic model. A rapid relaxation (t1/2 = 1-3 min) was elicited by all vasorelaxants. An apparent desensitization or fade of the relaxation response to nitroglycerin or isoproterenol was visualized as the partial regaining of tissue tone (t1/2 = 2-3 min). The relaxation responses to sodium nitroprusside or 5'-N-ethylcarboxamidoadenosine were stable for at least 60 min and did not exhibit an apparent regaining of tension. Tissues rendered desensitized by either isoproterenol or nitroglycerin responded fully to sodium nitroprusside or 5'-N ethylcarboxamidoadenosine. The rate constant for relaxation was vasorelaxant concentration-dependent and saturable for all vasorelaxants. For isoproterenol, nitroglycerin, and 5'-N-ethylcarboxamidoadenosine the rate constant for relaxation was inversely proportional to the contractile stimulus, as was the magnitude of relaxation for all vasorelaxants. Although the magnitude and rate constant of the fade was not concentration-dependent for isoproterenol, it was inversely proportional to the nitroglycerin concentration. The rate constant of the fade was proportional to the contractile stimulus for isoproterenol and nitroglycerin, and the magnitude of the fade was proportional to the contractile stimulus for nitroglycerin. We propose that kinetic studies of responses in isolated vasculature supersede studies performed under steady-state conditions, for they extend our knowledge of the manner by which the steady-state is achieved and allow for a quantitative analysis of the time-dependent changes which should assist in elucidating the biochemical basis of the observed physiological response. PMID- 1425988 TI - Inhibition of tetrahydroisoxazolo-pyridin-3-ol and muscimol and its mechanism on gastrointestinal transit in mice. AB - The effect of tetrahydroisoxazolo-pyridin-3-ol (THIP) and muscimol on gastrointestinal transit and a possible mechanism for this effect were studied using the charcoal meal test in mice. These agents inhibited transit dose relatedly. The inhibitory effect was completely reversed by yohimbine and phentolamine. A minor degree of antagonism by bicuculline was observed. There were an additive response in morphine-pretreated animals and partial antagonism in naloxone-pretreated animals. Propranolol failed to modify the inhibitory effect. The findings suggest a predominantly alpha 2-receptor-mediated inhibitory effect on gastrointestinal transit for THIP and muscimol which possibly also utilizes opioid pathways. However, it appears that beta-adrenergic and GABAergic systems might not contribute to this effect. PMID- 1425989 TI - The 5-HT2 receptor antagonist, MDL 28,133A, disrupts the serotonergic dopaminergic interaction mediating the neurochemical effects of 3,4 methylenedioxymethamphetamine. AB - The selective 5-HT2 receptor antagonist MDL 28,133A dose dependently-blocked the long-term deficits in rat brain 5-HT concentrations produced by the substituted amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA). This protective effect of MDL 28,133A could be abolished by coadministration of the dopamine precursor, L-dihydroxyphenylalanine (L-DOPA). Electrophysiological experiments demonstrated that the ability of MDL 28,133A to block the MDMA-induced slowing of A9 dopaminergic neurons was also sensitive to L-DOPA administration. Both sets of experiments suggest an interaction of MDL 28,133A at the level of dopamine synthesis. Consistent with this explanation, MDL 28,133A antagonized the MDMA induced stimulation of dopamine synthesis in vivo. MDMA-induced 5-HT release did not reduce the firing rate of dopaminergic neurons as assessed by dopamine depletion following synthesis inhibition with alpha-methyl-p-tyrosine (alpha MPT). This indicates that the effect of 5-HT2 receptor antagonists on MDMA induced dopamine synthesis is not due simply to the removal of an inhibitory serotonergic input followed by an increase in dopamine cell firing and autoreceptor activation. MDL 28,133A was also shown to be without effect on the sensitivity of terminal dopamine autoreceptors. The results are consistent with the hypothesis that 5-HT2 receptors are permissive for the stimulation of dopamine synthesis necessary to support MDMA-induced transmitter efflux. PMID- 1425990 TI - Synthesis and pharmacology of irreversible affinity labels as potential cocaine antagonists: aryl 1,4-dialkylpiperazines related to GBR-12783. AB - As part of a program aimed at designing irreversible antagonists of the stimulant and reinforcing properties of cocaine, derivatives of GBR-12783 containing electrophilic substituents were synthesized. GBR-12783, a potent and selective inhibitor of both stimulant binding and dopamine transport, was modified to incorporate either isothiocyanate or maleimido groups at the meta- or para positions in one phenyl ring of the geminal diphenyl portion of the molecule. The effect of these compounds, as well as their respective amino- or nitro substituted precursors, on stimulant binding to rat striatal tissue was studied using the [3H]methylphenidate radioreceptor assay. Under the assay conditions used, the compounds were found to have IC50s (nM) ranging from 11.9 (m-nitro) to 1677 (p-maleimido); the parent compound, GBR-12783, had an IC50 of 12.0. Using a washout technique (repeated washing with 100 mM KCl) which completely removed the tightly bound, but reversible GBR-12783, both the m- and p-isothiocyanate compounds were found to irreversibly inhibit binding of [3H]methylphenidate to the stimulant recognition site. The m-maleimido derivative also irreversibly inhibited binding, albeit with lower efficacy than was observed with the isothiocyanate compounds. Neither the p-maleimido, nor the amino or nitro intermediates, were capable of irreversible inhibition. PMID- 1425991 TI - The gamma-aminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats. AB - The effect of systemic administration of the gamma-aminobutyric acid (GABA) uptake inhibitor, R(-)N-(4,4-di(3-methyl-thien-2-yl)-but-3-enyl) nipecotic acid, hydrochloride (tiagabine) (previously NO-328), on extracellular GABA levels in the globus pallidus, ventral pallidum and substantia nigra of awake Sprague Dawley rats was investigated using in vivo microdialysis. Tiagabine was administered in doses of 11.5 or 21.0 mg/kg i.p. (ED50 and ED85 doses, respectively, for inhibiting pentylenetetrazole-induced tonic seizures). Tiagabine increased the extracellular concentrations of GABA in globus pallidus with peak values 310% of basal level (after 21 mg/kg) and 240% of basal level (after 11.5 mg/kg). A significant increase in extracellular GABA levels was also found in the ventral pallidum (280% increase after 11.5 mg/kg and 350% increase after 21 mg/kg) and in the substantia nigra where the ED85 dose of tiagabine (21 mg/kg) produced a peak value of 200% compared to the basal level. Thus, tiagabine acts as a GABA uptake inhibitor in vivo also. PMID- 1425992 TI - Protective effects of a 21-aminosteroid against copper-induced erythrocyte and plasma lipid peroxidation. AB - The 21-aminosteroids, or lazaroids, are a novel class of antioxidant drugs designed to inhibit iron-dependent lipid peroxidation in biological lipid environments. They have been shown to be of therapeutic value in several animal models of traumatic, ischemic and hemorrhagic injury of the central nervous system. Our purpose was to evaluate the ability of 21-aminosteroids to protect human erythrocytes and plasma against oxidative damage in vitro. We found that the 21-aminosteroid U74500A inhibited erythrocyte and plasma lipid peroxidation. U74500A at 1 microM significantly reduced copper-induced and hydrogen peroxide induced erythrocyte lipid peroxidation by 76.5 and 27.6%, respectively. The inhibition of erythrocyte lipid peroxidation was accompanied by an inhibition of hemolysis. Copper-induced plasma lipid peroxidation was also significantly reduced by as little as 1 microM U74500A. These results suggest that 21 aminosteroids may prove useful in preventive or therapeutic interventions in situations where erythrocyte or plasma components are subjected to oxidative stress and in situations related to copper-induced oxidative damage. PMID- 1425993 TI - Effects of the acute administration of a new trimethylxanthine derivative, S 9977 2, on local cerebral blood flow and glucose utilization in the rat. AB - S 9977-2 is a new trimethylxanthine derivative with promnesic properties. Its effects on cerebral glucose utilization and blood flow were studied by means of quantitative autoradiography. S 9977-2 was injected intravenously into adult rats at doses of 0.1, 1.0 and 10 mg/kg. At 0.1 mg/kg, S 9977-2 induced a significant increase in cerebral glucose utilization over control values in two white matter areas and in the vestibular nucleus. At 1.0 mg/kg, glucose utilization was affected in 14 areas out of the 63 studied, mainly limbic regions such as the hippocampus, raphe nuclei and locus coeruleus, as well as some posterior areas. Conversely, after the injection of 10 mg/kg S 9977-2, cerebral glucose utilization was similar to that of control rats. At the three doses tested, S9977 2 did not induce any significant variation in local rates of cerebral blood flow compared to those of controls. Likewise, S 9977-2 did not change the level of coupling between cerebral blood flow and metabolism, except at 10 mg/kg, where a relative hypoperfusion at a constant metabolic level was recorded. These data show that, at 1.0 mg/kg, S 9977-2 increased glucose utilization in hippocampal areas, an effect which may be related to the promnesic properties of this compound at the same dose. Moreover, at low doses, the lack of change in the level of coupling between cerebral blood flow and metabolism is indicative of the rather selective action of this compound, compared to that of caffeine. Thus S9977-2 should have therapeutic effects, mainly via its promnesic properties, without having many side effects. PMID- 1425995 TI - Possible prophylactic potential of HA1077, a Ca2+ channel antagonist and vasodilator, on chronic cerebral vasospasm. AB - We examined the possible prophylactic potential of HA1077, a calcium antagonist and vasodilator, on chronic cerebral vasospasm induced in a two-hemorrhage canine model, and also its effects on cerebral hemodynamics. The intravenous infusion of HA1077 3 mg/kg over 30 min twice daily (day 1-day 7) after the first intracisternal injection of 5 ml autologous blood significantly prevented the occurrence of chronic cerebral vasospasm. The mean diameter of the basilar arteries on day 7 was 66.1 +/- 1.6% (n = 7) of the baseline before the intracisternal injection of blood, compared to 54.2 +/- 1.6% (n = 9) of the baseline in the untreated group (P less than 0.01). Bolus intravenous administration of HA1077 (0.1 and 0.3 mg/kg) dose dependently increased local cerebral blood flow. Since HA1077 prevents the development of chronic cerebral vasospasm after subarachnoid hemorrhage and improves hemodynamic functions, as manifested by increases in local cerebral blood flow, further study is warranted regarding the possible clinical use of this drug. PMID- 1425994 TI - Effects of drugs on ventricular fibrillation and ischaemic K+ loss in a model of ischaemia in perfused guinea-pig hearts in vitro. AB - In a perfused guinea-pig heart model of myocardial ischaemia, reducing coronary flow by 95% for four successive 6 min periods caused a reproducible net loss of K+ into the coronary perfusate. This was reduced in a concentration-dependent manner by ATP dependent K+ channel blockers (glibenclamide and glipizide) and calcium channel blockers (verapamil and nifedipine). Other K+ channel blockers (UK-66,914, 4-aminopyridine, R56865 and phentolamine) and beta 1-adrenoceptor and beta 2-adrenoceptor antagonists (betaxolol and ICI118551) did not reduce this loss significantly. A single 30 min low-flow period reliably induced K+ release and ventricular fibrillation in control hearts. Glibenclamide, glipizide and phentolamine suppressed ventricular fibrillation but not ischaemic K+ loss in this model. R56865 and 4-aminopyridine and coadministration of betaxolol and ICI118551 yielded similar results while UK-66,914 suppressed neither. In our model, modulation of ischemic K+ loss and suppression of ventricular fibrillation were not closely associated and appeared to occur via separate mechanisms. PMID- 1425996 TI - Fantofarone (SR 33557): effect on post-ischaemic functional recovery in perfused rat hearts. AB - Fantofarone (SR 33557) is a novel, highly potent calcium channel antagonist representative of a new class of slow channel blockers. In this study, we have assessed its ability to influence cardiac function in two, isolated, perfused heart models and then assessed its ability to modify post-ischaemic functional recovery. In isolated, rat hearts perfused in the Langendorff mode, fantofarone increased coronary flow by 25% at 100 and 1000 nM with no effect on left ventricular pressure or heart rate below 100 nM. In working hearts, fantofarone again increased coronary flow within a similar concentration range. A significant reduction (approximately 40%) was observed in peak systolic pressure and dP/dtmax when hearts were perfused with 1000 nM fantofarone. Working rat hearts were also subjected to a 30 min period of global, low-flow (0.1 ml/min) ischaemia, followed by a 30 min period of reperfusion. Perfusion with 1 or 10 nM fantofarone, began 20 min prior to the onset of ischaemia and continued throughout the ischaemic and reperfusion periods. The addition of 1 nM fantofarone did not cause a significant increase in the recovery of cardiac function during the reperfusion phase. In contrast, perfusion with 10 nM fantofarone resulted in a substantial increase in the recovery of several indices of cardiac function such as aortic output, dP/dtmax and peak systolic pressure. Thus, in the working rat heart, at concentrations which cause minimal alterations to normal cardiac function, fantofarone can improve significantly functional recovery following an ischaemic insult. PMID- 1425997 TI - Structure-activity relationship of analogues of endothelin-1: dissociation of hypotensive and pressor actions. AB - The structural requirements of endothelin-1 to evoke depressor and pressor responses were studied in conscious rats. Formylation of the C-terminal Trp eliminated the depressor but not the pressor activity of endothelin-1. Oxidation of Met7 in this analogue restored the hypotensive activity. Destruction of the Cys1-Cys15 disulphide bridge led to a weak agonist with both depressor and pressor activities. Formylation of Trp21 in this analogue resulted in a complete loss of biological activity. These results indicate that Met7 and the indole moiety of Trp21 are important for the expression of the depressor activity of endothelin-1 whereas the intramolecular loop structure is less important. The results also provide further evidence that the depressor and pressor effects of endothelin-1 are mediated through different receptors. PMID- 1425998 TI - Enhancement of losartan (DuP 753)-induced angiotensin II receptor antagonism by PD123177 in rats. AB - Losartan (DuP 753) and PD123177 are angiotensin II type 1 (AT1) and type 2 (AT2) receptor selective ligands, respectively. In rats, PD123177 did not exhibit angiotensin II antagonism or hypotensive activity but enhanced these activities of a submaximal dose of losartan. As PD123177 displaced losartan from its rat plasma protein binding sites and thus increased the free concentration of losartan, this may account for its enhancement of the in vivo activities of losartan in rats. PMID- 1425999 TI - Nitric oxide induces neurotransmitter release from hippocampal slices. AB - Hydroxylamine (1-300 microM), a nitric oxide generator, stimulated the release of [3H]norepinephrine ([3H]NE) and [14C]acetylcholine ([14C]ACh) from rat hippocampal slices in a concentration-dependent manner (EC50 approximately 30 microM). A maximally effective concentration of hydroxylamine (300 microM) produced a 24-fold increase in the basal [3H]NE and 3.6-fold increase in the in the basal [14C]ACh efflux. Sodium nitroprusside (SNP), also stimulated the release of [3H]NE, but only at high concentrations (10-30 mM). Calcium-free experimental buffer (1 mM EGTA) abolished the response. Hemoglobin (0.3 microM) inhibited the effect of 100 microM hydroxylamine in a manner which was specific for nitric oxide. In addition, 100 microM hydroxylamine increased the efflux of endogenous GABA and glutamate by 3- and 6-fold, respectively. PMID- 1426000 TI - Effects of baicalein and alpha-tocopherol on lipid peroxidation, free radical scavenging activity and 12-O-tetradecanoylphorbol acetate-induced ear edema. AB - The effects of baicalein, a flavonoid, and alpha-tocopherol (vitamin E) on lipid peroxidation in rat forebrain homogenates, on free radical scavenging action against diphenyl-p-picrylhydrazyl (DPPH), and on 12-O-tetradecanoylphorbol acetate (TPA)-induced ear edema in mice were studied. Baicalein inhibited lipid peroxidation in forebrain homogenates, DPPH-induced free radical and TPA-induced ear edema as potently as did quercetin and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and more potently than BW755C, a mixed cyclooxygenase and lipoxygenase inhibitor. Lipid peroxidation in forebrain homogenates, DPPH-induced free radical and TPA-induced ear edema were also inhibited by alpha-tocopherol. Flavone showed no reaction. These results suggest that lipid peroxidation may play an important role in the pathogenesis of TPA-induced ear edema in mice. PMID- 1426001 TI - Cholecystokinin octapeptide alters morphine-induced effects on EEG power spectra both quantitatively and qualitatively. AB - In the present study, EEG analysis was used to determine if cholecystokinin octapeptide (CCK-8) has an effect on the EEG spectral profile associated with morphine-induced bursting. Adult female Sprague-Dawley rats were implanted with cortical electrodes and indwelling i.c.v. and i.v. cannulas. On the day of the experiment, each rat received an i.c.v. injection of either H2O or one of four doses of CCK-8: 8.0, 16.0, 32.0 or 64.0 ng. Ten minutes after receiving the i.c.v. injection, each rat received a 10.0 mg/kg dose of morphine by i.v. injection. Neither the i.c.v. injections of H2O nor CCK-8 produced any EEG bursting or behavioral stupor. However, the i.v. injection of morphine produced high-voltage, slow-wave EEG bursts in all rats. Analysis of EEG recorded during bursting showed that both the 32.0 and 64.0 ng doses of CCK-8 increased absolute power associated with morphine-induced bursting, and comparison of the distribution of power across the range of frequency bands between the control (H2O) and the 32.0 ng dose of CCK-8 revealed that CCK-8 caused a significant change in the pattern of distribution of power. Furthermore, significant dose related differences were found in the global (1-50 Hz) parameters absolute power, mean frequency, mobility, complexity and edge frequency. Significant differences among the five groups were not found in the parameter of peak frequency, or in either latency to slow-wave sleep or duration of morphine-induced bursting. These results demonstrate that CCK-8 caused both quantitative and qualitative changes in the EEG spectral profile associated with morphine-induced bursting. PMID- 1426002 TI - Marked inhibition of mesolimbic dopamine release: a common feature of ethanol, morphine, cocaine and amphetamine abstinence in rats. AB - Withdrawal of rats from chronic ethanol, morphine, cocaine and amphetamine resulted in a marked reduction in extracellular dopamine (DA) concentration in the ventral striatum as measured by microdialysis. Following ethanol and naloxone precipitated morphine withdrawal, the time course of DA reduction paralleled that of the withdrawal symptomatology. On the other hand, following discontinuation of chronic cocaine, DA reduction was delayed by over 24 h but persisted for several days. After amphetamine withdrawal the fall in DA occurred more rapidly but the reduction also persisted for several days. The administration of the NMDA receptor antagonist, MK-801, to rats withdrawn from chronic ethanol, morphine or amphetamine, but not from chronic cocaine, readily reversed the fall in DA output. The reduction in extracellular DA during ethanol withdrawal was also reversed by SL 82.0715, another NMDA receptor antagonist. PMID- 1426003 TI - Vasodilatory effects of adenosine A2 receptor agonists CGS 21680 and CGS 22492 in human vasculature. AB - The vasodilatory effects of the adenosine analogs, 5'-N-ethylcarboxamidoadenosine (NECA), 2-[p-(2-carboxyethyl)phenethyl amino]-5'-N-ethylcarboxamidoadenosine (CGS 21680) and 2-[(2-cyclohexylethyl)amino]adenosine (CGS 22492) in human coronary, internal mammary artery and saphenous vein were examined in vitro. All produced concentration-dependent relaxations in arterial as well as venous rings contracted with 35 mM KCl. The concentration-response curves for NECA and CGS 21680 were parallel in the coronary. The adenosine A2 receptor antagonist, 9 chloro-2-(2-furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS 15943A) significantly attenuated the relaxing response to the adenosine analogs in coronary artery. Although NECA and CGS 22492 were equally as effective at the highest concentration administered (both achieving approximately 70% relaxation at 10(-4) M) NECA (EC50 = 1.25 +/- 0.11 microM) induced greater vasodilation at lower concentrations than CGS 22492 (EC50 = 11.27 +/- 1.53 microM). CGS 21680 was the least potent of the agents tested achieving only 44% relaxation at 10(-4) M (EC50 = 4.71 +/- 0.46 microM). Coronary artery appeared to be more responsive than internal mammary artery or saphenous vein which displayed only marginal relaxation to these agents. PMID- 1426004 TI - Assessment of the role of adrenoceptor function in ischemia-induced impairment of 2-deoxyglucose uptake and CA1 field potential in rat hippocampal slices. AB - The release of catecholamines, dopamine and noradrenaline has been suggested to play a role in mediating ischemic damage in susceptible brain regions, the hippocampus and striatum. We now provide evidence that suggests a role for adrenoceptors in the deficit of 2-deoxyglucose uptake and CA1 field potential induced in hippocampal slices by hypoxia/hypoglycemia (ischemia). Treatment with alpha 1- or beta-adrenoceptor agonists or cAMP potentiated an ischemia-induced decline of both 2-deoxyglucose uptake and CA1 field potential in hippocampal slices, whereas alpha 1- or beta-adrenoceptor antagonists, or alpha 2 adrenoceptor agonists produced a remarkable neuroprotective action against these deficits. The results indicate that stimulation of adrenoceptors may play a detrimental role in the development of ischemic damage, and suggest a neuroprotective action for adrenoceptor antagonists, which may lessen the functional deficits induced by ischemia. PMID- 1426005 TI - Evidence for a direct vasoconstrictor effect of big endothelin-1 in the rat kidney. AB - Inhibition of endothelin-1 (ET-1)-converting enzyme has been suggested as a strategy for blocking ET-1-mediated vasoconstriction. However, it is unclear whether its putative substrate, bigET-1, is an inactive precursor. Thus, we compared in the rat the effects of ET-1 and bigET-1 on renal vascular resistance (RVR) in vitro (isolated perfused kidney, n = 15) and in vivo (Doppler shift technique, n = 23) when injected i.v. or in the rat renal artery (i.a.), before and after metalloprotease inhibition with phosphoramidon (30 mg/kg i.v.). In vitro, the ET-1/bigET-1 potency ratio for the RVR increase was 175; in vivo (i.v.) it was approximately 7 (ED50: 99 and 692 pmol/kg, respectively; P < 0.01). Unlike that of ET-1, the bigET-1 effect started slowly (peak effect at 15 min). On i.a. injection, the ED50 of ET-1 was lower but that of big ET-1 was unchanged (ED50: 28 and 706 pmol/kg, respectively). Moreover, the effect of i.a. bigET-1 on RVR was biphasic, with a dose-related rapid increase followed by a slowly developing further rise. Phosphoramidon completely inhibited the hemodynamic effects of i.v. bigET-1, but abolished only the second phase of the response when given i.a. It also significantly enhanced the effect of ET-1. We conclude that in the rat: (1) bigET-1 may affect RVR by both a direct effect and through phosphoramidon-sensitive conversion to ET-1; (2) the direct vasoconstrictor effect of bigET-1 might be expressed during endothelin-converting enzyme inhibition; (3) metalloproteases are involved in ET-1 degradation. PMID- 1426006 TI - NMDA receptor antagonists protect against seizures and wet-dog shakes induced by 4-aminopyridine. AB - The effect of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on the generalized tonic-clonic convulsions and wet-dog shakes induced by the intraperitoneal (i.p.) or the intrahippocampal (i.h., stereotaxic microinjection into the CA1 region) administration of 4-aminopyridine (4-AP) was studied in rats. Pretreatment with NMDA competitive and non-competitive antagonists resulted in potent protection against the motor effects of both the i.p. and the i.h. administration of 4-AP. MK-801 (0.25 mg/kg i.p.) and 3-(2-carboxypiperazin-4 yl)propyl-1-phosphonic acid (CPP, 0.8 nmol intracerebroventricular, i.c.v.) showed the most powerful anticonvulsive effect, since they prevented the occurrence of generalized tonic convulsions and the death of the animals in convulsions after i.p. 4-AP. The i.c.v. injection (10 nmol) of the NMDA competitive antagonists 2-amino-5-phosphonopentanoate (AP-5) and 2-amino-5 phosphonoheptanoate (AP-7) also showed a clear though less potent protective effect. Similarly, the frequency of wet-dog shakes induced by i.h. 4-AP was markedly decreased by pretreating the animals with i.p. MK-801 or with i.c.v. CPP or AP-7. However, the co-injection of CPP with 4-AP failed to protect against the occurrence of wet-dog shakes. The i.c.v. pretreatment with the unselective antagonist, kynurenate (up to 68 nmol) or with the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (0.5 nmol), did not significantly modify the effects of 4-AP when administered either i.p. or i.h. We conclude that NMDA receptors are involved in the mechanism of the convulsive activity induced by 4 AP, probably because this drug induces the release of glutamate. PMID- 1426007 TI - Antagonism of pre- and postjunctional responses to neuropeptide Y and sympathetic stimulation by D-myo-inositol-1,2,6-trisphosphate in the anaesthetised dog. AB - Pre- and postjunctional responses to nerve released or exogenous neuropeptide Y (NPY) were measured in the anaesthetised dog before and after administration of D myo-inositol-1,2,6-trisphosphate (PP56) a putative NPY antagonist. The inhibition of the increase in pulse interval evoked by vagal stimulation was used as a measure of prejunctional action of NPY and the magnitude of increase in blood pressure was used as a measure of postjunctional action of NPY (direct action or constrictor potentiating). Elevated plasma levels of PP56 were maintained throughout the course of the experiment. PP56 significantly reversed the inhibitory effect of NPY (nerve released or exogenous) on cardiac vagal action, and significantly inhibited the pressor response to exogenous NPY. PP56 did not affect the pressor response to intravenous phenylephrine, a selective alpha adrenoceptor agonist. PP56 therefore significantly antagonises both pre- and postjunctional effects of NPY (nerve released and exogenous) and, with respect to its postjunctional antagonism, this action is selective for NPY. PMID- 1426008 TI - Regional vasodilation to endothelin-1 is mediated by a non-ETA receptor subtype in the anaesthetized rat: effect of BQ-123 on systemic haemodynamic responses. AB - The sustained infusion of 75 nmol/kg per min BQ-123 selectively attenuates the systemic pressor responses to i.v. bolus endothelin-1 in the anaesthetized rat; the initial systemic vasodepression is only attenuated when a 10-fold higher dose of this ETA-selective antagonist is infused. These doses of BQ-123 do not antagonize the haemodynamic actions of angiotensin II or calcitonin gene-related peptide nor do they alter basal systemic haemodynamics. The secondary increase in carotid vascular resistance associated with the systemic pressor actions of endothelin-1 is selectively attenuated by the bolus i.v. administration of BQ-123 (1.6 mumol/kg); the maximum degree of the vasorelaxation that precedes this more sustained constriction is unaltered. Thus, the initial carotid vasodilation observed to endothelin-1, and the associated systemic vasodepression, is mediated by a non-ETA receptor subtype. Furthermore, subtle differences might exist between the receptors mediating mesenteric and carotid vasoconstriction since only the latter is sensitive to BQ-123. PMID- 1426009 TI - The effect of histamine on cultured endothelial cells. A study of the mechanism of increased vascular permeability. AB - The role of endothelial cells in the histamine-induced vascular response was investigated using cultured endothelial cells obtained from human umbilical veins. A single population of histamine H1 receptors was detected in these cells by means of a [3H]mepyramine binding assay. Its Kd was 0.74 +/- 0.07 nM and Bmax was 41.4 +/- 8.68 fmol/mg protein. Actin filaments were distributed as dense bands at the margin of the cells and as sparse microfilament bundles traversing the center of the cells. Histamine caused a decrease in peripheral bands and an increase in longitudinal bands. The changes evoked by histamine were dose dependent, related to the duration of incubation of the cells with histamine, and blocked by mepyramine, a histamine H1 receptor antagonist. The results suggest that the endothelial cells respond to histamine through the histamine H1 receptor. This may explain one of the mechanisms of histamine-induced vascular response including vascular permeability increase. PMID- 1426010 TI - The effects of 5-HT3 receptor antagonists on cisplatin-induced emesis in the pigeon. AB - In the present study, the emetic effect of the anticancer drug cisplatin, and the protective effects of 5-HT3 receptor antagonists against cisplatin emesis were investigated in the pigeon. The experimental set-up involved the i.v. administration of drugs and subsequent observation of the percentage of vomiting animals and the number of emetic episodes per vomiting animal. It was observed that cisplatin induced dose-dependent emesis in the pigeon. 5-HT3 receptor antagonists afforded partial protection against cisplatin emesis, although some of them, i.e. indole, indole-like derivatives and zacopride, displayed intrinsic emetic activity. A serotonergic mechanism appears to be involved in both cisplatin- and 5-HT3 receptor antagonist-induced emesis, since pretreatment with an inhibitor of 5-HT synthesis, para-chlorophenylalanine (pCPA), prevented vomiting induced by either cisplatin or 5-HT3 receptor antagonists. It is concluded that the intrinsic emetic effects of 5-HT3 receptor antagonists provide pharmacological evidence of species differences in the properties of 5-HT3 receptors. PMID- 1426011 TI - Effects of a peripheral-type benzodiazepine on glucose-induced insulin secretion. AB - Benzodiazepines, besides interacting with central-type receptors which mediate their well-known pharmacological actions, bind to peripheral-type receptors that are distributed in a variety of peripheral tissues including numerous endocrine organs. The present work was designed to investigate the effects of a selective peripheral-type benzodiazepine, 4'-chlordiazepam (Ro 5-4864), on glucose-induced insulin secretion in vitro. In the rat isolated pancreas perfused with a Krebs bicarbonate buffer containing 8.3 mM glucose, the drug (10(-6) and 10(-5) M) induced a progressive and significant decrease in insulin release. Concomitantly, it induced a vasodilator response of the pancreatic vascular bed. In rat isolated islets incubated for 1 h in the presence of 15 mM glucose, 4'-chlordiazepam (10( 5) and 10(-4) M) induced a significant and dose-dependent inhibition of insulin release. In contrast, the selective central-type benzodiazepine, clonazepam (10( 6) - 10(-4) M), did not significantly modify glucose-induced insulin secretion. In addition, experiments were performed to test the effect of 1-(2-chlorophenyl) N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamid e (PK 11195), a peripheral non-benzodiazepine ligand proposed as a putative antagonist. This substance did not counteract the inhibitory effect of 4'-chlordiazepam but itself (10(-6) and 10(-5) M) elicited a potent inhibitory effect on insulin secretion. These results show that drugs such as 4'-chlordiazepam and PK 11195 which have a high affinity for peripheral-type benzodiazepine receptors, in contrast to a central-type benzodiazepine agonist, inhibit glucose-induced insulin secretion in vitro. PMID- 1426012 TI - Plasma glucose levels predict the disrupting effects of adrenoceptor antagonists on enhancement of memory storage. AB - Adrenoceptor antagonists block the enhancement of memory storage produced by epinephrine injection, but not that produced by glucose injection. The present experiment determined whether adrenoceptor antagonists modify resting blood glucose levels or the magnitude of epinephrine-, glucose-, and footshock-induced increases in circulating glucose levels in a manner related to these previously observed effects on memory. The alpha- and beta-adrenoceptor antagonists, phenoxybenzamine and propranolol, respectively, were injected in rats 30 min prior to administration of epinephrine, glucose, or footshock. Plasma glucose levels were sampled during the next 30 min. Epinephrine-induced increases in plasma glucose levels were potentiated by phenoxybenzamine and were attenuated and delayed by propranolol. The adrenoceptor antagonists did not alter resting plasma glucose levels, or the increases in plasma glucose levels resulting from glucose injection or footshock. These findings suggest that phenoxybenzamine and propranolol alter blood glucose responses to epinephrine injection in a manner which may contribute to attenuation of epinephrine-induced enhancement of memory storage with peripheral injections of adrenoceptor antagonists. PMID- 1426013 TI - Suppression by cholinesterase inhibition of a Ca(2+)-independent efflux of [3H]acetylcholine from the neuromuscular junction of the isolated rat diaphragm. AB - Endplate preparations of the left rat hemidiaphragm were incubated with [3H]choline to label neuronal acetylcholine stores. Elevation of the concentration (13.5-135 mmol/l) of extracellular potassium chloride (KCl) stimulated the release of [3H]acetylcholine in a concentration-dependent manner. KCl (27 mmol/l) still caused a significant efflux of [3H]acetylcholine in a Ca(2+)-free medium. Inhibitors of cholinesterase (physostigmine, diisopropylfluorophosphate) suppressed by 80% this Ca(2+)-independent efflux of [3H]acetylcholine. Vesamicol (10 mumol/l), the blocker of the vesicular acetylcholine carrier, also suppressed the stimulated, Ca(2+)-independent efflux of [3H]acetylcholine. The inhibitory effect of physostigmine was not prevented by muscarine or nicotine receptor antagonists, but the inhibitory effect was lost when the stimulus strength was increased (81 mmol/l KCl). The present experiments showed cholinesterase inhibition to suppress a Ca(2+)-independent efflux of [3H]acetylcholine, probably by interference with a membrane-bound acetylcholine carrier. PMID- 1426014 TI - Inhibitory effect of curcumin, an anti-inflammatory agent, on vascular smooth muscle cell proliferation. AB - The effects of curcumin, an anti-inflammatory agent from Curcuma longa, on the proliferation of blood mononuclear cells and vascular smooth muscle cells were studied. Proliferative responses were determined from the uptake of tritiated thymidine. In human peripheral blood mononuclear cells, curcumin dose dependently inhibited the responses to phytohemagglutinin and mixed lymphocyte reaction at the dose ranges of 10(-6) to 3 x 10(-5) and 3 x 10(-6) to 3 x 10(-5) M, respectively. Curcumin (10(-6) to 10(-4) M) dose dependently inhibited the proliferation of rabbit vascular smooth muscle cells stimulated by fetal calf serum. Curcumin had a greater inhibitory effect on platelet-derived growth factor stimulated proliferation than on serum-stimulated proliferation. Cinnamic acid, coumaric acid and ferulic acid were much less effective than curcumin as inhibitors of serum-induced smooth muscle cell proliferation, suggesting that the cinnamic acid and ferulic acid moieties alone are not sufficient for activity, and that the characteristics of the diferuloylmethane molecule itself are necessary for activity. Curcumin may be useful as a new template for the development of better remedies for the prevention of the pathological changes of atherosclerosis and restenosis. PMID- 1426015 TI - The effect of endogenous nitric oxide on neurogenic plasma exudation in guinea pig airways. AB - We studied the effect of endogenous nitric oxide (NO) on vagally induced plasma exudation into guinea-pig trachea and main bronchi using 125I-albumin as a plasma marker. NG-Nitro-L-arginine methyl ester (L-NAME, 1-10 mg/kg) dose dependently inhibited neurogenic plasma exudation. Intravenous phenylephrine which simulated the vasopressor effect as L-NAME (10 mg/kg) was without effect. The effect of L NAME (5 mg/kg) was reversed by L-arginine (50 mg/kg). These results suggest that endogenous NO may contribute to neurogenic inflammation in the airways. PMID- 1426016 TI - Preferential release of epinephrine by glycine from adrenal chromaffin cells. AB - Isolated adrenal chromaffin cells were used as a model for the release of catecholamines from adrenergic nerve endings. In this study we used an HPLC technique to determine the effects of acetylcholine and glycine on norepinephrine and epinephrine release. The amount of catecholamine released in response to glycine was 22% less than that released by acetylcholine. However, while the norepinephrine-to-epinephrine ratio was 1.6 after stimulation with acetylcholine, it was 0.6 after stimulation with glycine. This suggests that glycine preferentially affects epinephrine secretion as compared to acetylcholine, which preferentially releases norepinephrine. This differential effect could be of physiological importance considering our recent demonstration of a functional high-affinity chloride-gated glycine receptor on adrenal chromaffin cells. PMID- 1426017 TI - Clozapine has sub-micromolar affinity for 5-HT1A receptors in human brain tissue. AB - The affinities of a range of antipsychotic drugs at human hippocampal 5-HT1A receptors, defined by specific [3H]8-OH-DPAT binding, were determined. Clozapine demonstrated the highest affinity; all other antipsychotics studied demonstrated pK(i) values below 6.0 5-HT1A receptors are found on cortical glutamatergic neurons, a dysfunction of which may occur in schizophrenia. Binding at this site indicates a possible mechanism contributing to the unique efficacy of clozapine in the treatment of some schizophrenic patients. PMID- 1426018 TI - NG-nitro-L-arginine prevents morphine tolerance. AB - NMDA receptor antagonists, such as MK-801, prevent the development of tolerance to morphine. Since many NMDA actions involve the production of nitric oxide, we examined the effects of a nitric oxide synthase inhibitor on morphine tolerance. The analgesic response to morphine (5 mg/kg s.c.) given daily diminishes from 60% in naive animals to 0% within 5 days. Coadministration of NG-nitro-L-arginine (8 mg/kg per day) along with morphine prevents the demonstration of appreciable tolerance for at least 11 days. These results suggest that morphine tolerance involves the activation of NMDA receptors followed by the subsequent release of nitric oxide. PMID- 1426019 TI - Marked decrease of A10 dopamine neuronal firing during ethanol withdrawal syndrome in rats. AB - The electrophysiological activity of mesoaccumbens dopaminergic neurons was monitored during the ethanol-withdrawal syndrome in ethanol-dependent and in control rats. Spontaneous firing was reduced by about half in ethanol-dependent rats as compared to controls. Likewise, the number of spikes/burst was also reduced in ethanol-dependent rats. These results are consistent with the reduction in dopamine release observed during ethanol-withdrawal syndrome and may provide the basis for the aversive effects of the ethanol-withdrawal syndrome. PMID- 1426020 TI - gp120 of HIV-1 induces apoptosis in rat cortical cell cultures: prevention by memantine. AB - After incubation of rat cortical cell cultures with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 12 h, cells showed fragmentation of DNA at internucleosomal linkers, the characteristic feature of apoptosis. In a quantitative approach, it was determined that the percentage of DNA fragmentation increased from 7%, in the absence of gp120, to 62% following incubation with 24 ng/ml of gp120. Simultaneously, the percentage of viable cells decreased from 94% to 33%. Memantine (1-amino-3,5-dimethyladamantane), a drug currently used in the therapy of spasticity and Parkinson's disease as well as the NMDA antagonist MK 801 both prevented the effects of gp120 at micromolar concentrations. In human cultured astrocytes, gp120 was ineffective with respect to DNA fragmentation and cell toxicity. From these data, we conclude that the gp120-induced apoptosis may contribute to the neurological complications frequently associated with the immunodeficiency syndrome. The cytoprotective effect of memantine in cortical cell cultures may qualify the drug for the treatment of AIDS-related dementia. PMID- 1426021 TI - Separation and purification by two-dimensional gel electrophoresis of a 52-54 kDa bumetanide binding protein from rat liver plasma membranes. AB - By affinity labeling with photolabile [3H]bumetanide, a 52-54 kDa bumetanide binding protein was identified in the sinusoidal plasma membrane fraction from rat liver. The protein is assumed to represent the carrier for hepatic uptake of loop diuretics. By two-dimensional (2D) gel electrophoresis we have purified this protein from hepatocytes, sinusoidal plasma membranes and subfractions of associated and integral plasma membrane proteins. Amongst more than 20 protein spots, a single integral plasma membrane protein was detected. The apparent pI of this molecule is 6.7. Specific labeling of this protein was not found in the fraction of associated plasma membrane proteins. To detect possible binding of radioactive bumetanide to microsomal cytochrome P450s, photolabeling experiments with integral plasma membrane proteins were performed under nitrogen/carbon monoxide atmosphere and in the presence of piperonyl butoxide. Labeling of the 52 54 kDa protein was not affected by these inhibitors of P450 enzymes. Taken together, these results indicate that the bumetanide binding protein is very likely to be a non-microsomal integral plasma membrane protein. PMID- 1426022 TI - 3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid decreases NMDA receptor mRNA. AB - Expression of the N-methyl-D-aspartate receptor gene during long-term administration of competitive and non-competitive NMDA antagonists was studied in rat brain using antisense cRNA transcribed from reverse transcriptase-polymerase chain reaction (RT-PCR)-generated rat NMDA receptor cDNA. Unlike non-competitive antagonists, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) markedly decreased NMDA receptor mRNA steady-state concentrations in frontal cortex and hippocampus. Our results are consistent with a regulation of the NMDA receptor at the level of gene expression. PMID- 1426023 TI - Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors. AB - We investigated the binding properties of the (R)- and (S)-enantiomers of the muscarinic antagonists trihexyphenidyl, procyclidine, hexahydro-difenidol, p fluoro-hexahydro-difenidol, hexbutinol, p-fluoro-hexbutinol, and their corresponding methiodides at muscarinic M1, M2, M3 and M4 receptor subtypes. In addition, binding properties of the (R)- and (S)-enantiomers of oxyphencyclimine were studied. The (R)- enantiomers (eutomers) of all the compounds had a greater affinity than the (S)-isomers for the four muscarinic receptor subtypes. The binding patterns of the (R)- and (S)-enantiomers were generally different. We did not observe any general correlation between the potency of the high-affinity enantiomer and the affinity ratio (eudismic ratio) of the two enantiomers. The results are discussed in terms of a 'four subsites' binding model. PMID- 1426024 TI - Characterization of rat glomerular thromboxane A2 receptors: comparison to rat platelets. AB - This study was designed to characterize rat glomerular thromboxane A2 (TxA2) receptors and compare them to rat platelet TxA2 receptors. The radioligand binding characteristics of the receptors were characterized using [125I][1S-(1 alpha,2 beta(5Z),3 alpha-(1E,3R*),4 alpha]-7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1 butenyl)-7-oxabicyclo- [2.2.1]heptan-2yl]-5-heptenoic acid ([125I]BOP), a TxA2 agonist. Equilibrium binding with [125I]BOP, as well as competitive binding assays between [125I]BOP and 13-azapinane TxA2 receptors antagonists, were performed in rat glomerular membranes (RGM) and washed rat platelets (WRP). [125I]BOP identified a single class of TxA2 receptor sites in glomerular membranes with a Kd of 318 +/- 55 pM and a Bmax of 260 +/- 62 fmol/mg protein (n = 14). [125I]BOP was displaced by the TxA2 agonist 15S-hydroxy-11 alpha,9 alpha(epoxymethano)-prosta-5Z,13E-dienoic acid (U-46,619) (IC50 = 22 +/- 6 nM, n = 3), the antagonist SQ-29,548 (IC50 = 41 +/- 7 nM, n = 4), and stereoselectively by the antagonists (-)-9-chlorobenzyl-6-fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid (L-657,925) (IC50 = 0.27 +/- 0.04 nM, n = 3) and (+)-9-chlorobenzyl-6 fluoro-1,2,3,4-tetrahydrocarbazol-1-yl acetic acid (L-657,926) (IC50 = 124 +/- 0 nM, n = 2). The ability of six 13-azapinane TxA2 antagonists to compete with [125I]BOP was evaluated. The rank orders for the 13-azapinanes showed no significant correlation between RGM and WRP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426026 TI - Differential effects of cytochrome P-450 induction on ligand binding to sigma receptors. AB - The identity of the sigma receptor as a form of cytochrome P-450 was investigated in rats treated with 3-methylcholanthrene or phenobarbital. The density of [3H]N,N'-di(o-tolyl)guanidine (DTG) binding to sigma 2 receptors in hepatic subcellular fractions increased following both treatments, while [3H](+) pentazocine binding to sigma 1 receptors was unchanged. Furthermore, proadifen and piperonyl butoxide inhibited [3H](+)-pentazocine and [3H]DTG binding with low potency. The low affinity of cytochrome P-450 inhibitors for sigma receptors, the similar degree of enhancement of [3H]DTG binding by agents with disparate cytochrome P-450 induction profiles and the lack of change in [3H](+)-pentazocine binding are inconsistent with the identity of the sigma receptor as a cytochrome P-450. PMID- 1426025 TI - Modulation of [3H]3-((+-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) binding by ligands acting at the glycine and the polyamine sites of the rat brain NMDA receptor complex. AB - The competitive N-methyl-D-aspartate (NMDA) receptor antagonist [3H]3-((+-)-2 carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) interacts with two discrete binding sites, one of high- and the other of low-affinity, on rat forebrain synaptic plasma membranes. The high affinity site exhibited a Kd of 101.5 nM and a Bmax of 2.01 pmol/mg, while for the low affinity site the Kd was 4.11 microM with a Bmax of 19.7 pmol/mg. The glycine site antagonists 3-amino-1 hydroxy-2-pyrrolidone (HA-966), 1-aminocyclobutanecarboxylic acid (ACBC), the glycine site agonist 1-aminocyclopropanecarboxylic acid (ACC) and glycine itself (as well as the polyamines spermine and spermidine), enhanced [3H]CPP binding. When subjected to saturation analysis, this enhancement was found primarily to involve an increase in the affinity of the high affinity component of [3H]CPP binding. Neither of the parameters of the low affinity component of binding were affected. Although a similar enhancement was observed with the polyamines, the effects of these two classes of ligands were additive, consistent with their having actions at different recognition sites on the NMDA receptor complex. PMID- 1426027 TI - Protein kinase C-dependent and -independent actions of a potent protein kinase C inhibitor, staurosporine. AB - 12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C (PKC), induced ornithine decarboxylase (ODC) in primary cultured mouse epidermal cells. Staurosporine, a potent protein kinase C inhibitor, also induced ODC activity. Both TPA- and staurosporine-caused ODC inductions were markedly suppressed in the PKC-down-regulated cells. Another PKC inhibitor, 1-(5 isoquinolinesulfonyl)-2-methylpiperazine (H-7), inhibited both TPA- and staurosporine-caused ODC inductions. H-7 by itself never induced ODC activity. Under our experimental conditions, staurosporine induced no detectable phosphorylation of endogenous proteins. TPA induced a translocation of PKC from cytosol to membrane whereas an optimal concentration of staurosporine to induce ODC did not induce an obvious translocation of PKC. Indomethacin, a cyclooxygenase inhibitor, inhibited staurosporine-caused ODC induction, but not TPA-caused ODC induction. Staurosporine induced specific morphological changes of epidermal cells both in normal and in PKC-down-regulated cells. These results indicate that staurosporine induces ODC activity in a PKC-dependent manner and morphological changes possibly through a PKC-independent mechanism. The mechanism of ODC induction caused by staurosporine may be in some way different from that caused by TPA. PMID- 1426028 TI - Norepinephrine-induced Ca2+ current inhibition in adult rat sympathetic neurons does not require protein kinase C activation. AB - Experiments were performed to investigate if protein kinase C is involved in the norepinephrine-induced alpha 2-adrenoceptor-mediated inhibition of the Ca2+ current in adult rat superior cervical ganglion neurons. Ca2+ currents were recorded from dispersed superior cervical ganglion neurons, acutely isolated from adult rats, using the whole-cell patch-clamp technique. Both norepinephrine and the protein kinase C activator, 1,2-dioctanoylglycerol (diC8) decreased the Ca2+ current induced by step depolarizations to +10 mV from a holding potential of -80 mV. In the presence of norepinephrine, the Ca2+ current rising phase was adequately fit by a double exponential with a second time constant much larger than control, whereas in the presence of diC8 the rising phase became mono exponential and the current displayed a prominent decay. Control tail current activation curves were described by the sum of two Boltzmann functions. Both norepinephrine and diC8 reduced peak tail current amplitude. Norepinephrine preferentially reduced the component activated at more hyperpolarized potentials, while diC8 preferentially reduced the component activated at more depolarized potentials. Intracellular application of three protein kinase C inhibitors: protein kinase C pseudosubstrate (PKC-19-36) (2 microM), staurosporine (1 microM) and 1-(5-isoquinolinylsulonyl)-2-sulfonylpiperazine (H-7) (50 microM), failed to affect norepinephrine-induced Ca2+ current inhibition. In addition, these protein kinase C inhibitors did not decrease the Ca2+ current inhibition induced by diC8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426029 TI - Differences in activities of thromboxane A2 receptor antagonists in smooth muscle cells. AB - Thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors were characterized in rat vascular smooth muscle cells (VSMC). The specific binding of [3H]SQ 29,548 was inhibited by KW-3635, a novel non-prostanoic TXA2 antagonist, SQ 29,548 and BM 13505 (daltroban). SQ 29,548 showed a single class of binding sites with a Ki value of 1.6 nM. The inhibition patterns were better fit to two-component curves for KW-3635 (Ki values of 0.45 nM and 42 nM) and BM-13505 (2.3 nM and 20 nM). U46619, a TXA2 agonist, induced an increase in intracellular calcium concentration ([Ca2+]i), which was inhibited by these antagonists. KW-3635 and SQ 29,548 did not induce any increase in [Ca2+]i, whereas BM-13505 was found to induce a smaller increase in [Ca2+]i. The BM-13505-induced increase in [Ca2+]i was also inhibited by pretreatment with KW-3635, SQ 29,548 and BM-13505. The results demonstrate that BM-13505 has partial agonistic activity on TXA2/PGH2 receptors, and KW-3635 and SQ 29,548 do not. SQ 29,548 and BM-13505 inhibited both U-46619- and BM-13505-induced increases in [Ca2+]i to a similar degree. Alternatively, KW-3635 inhibited a U46619-induced increase in [Ca2+]i more effectively than a BM-13505-induced increase. These results suggest the heterogeneity of functional binding sites or subtypes of TXA2/PGH2 receptors present in VSMC. PMID- 1426030 TI - Losartan inhibits the angiotensin II-induced stimulation of the phosphoinositide signalling system in vascular smooth muscle cells. AB - 2-n-Butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl-4 yl)methyl]imidazole, potassium salt (Losartan) (previous name, DuP 753 or MK 954) is a nonpeptide angiotensin II receptor antagonist. This study was performed to investigate the ability of Losartan to inhibit the angiotensin II-induced stimulation of the phospoinositide signalling system and the angiotensin II induced hypertrophy in aortic vascular smooth muscle cells of normotensive Wistar Kyoto rats. 10(-7) M Losartan abolished the angiotensin II-induced formation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. 10(-6) M Losartan completely abolished the angiotensin II-induced elevation of the intracellular free Ca2+ concentration ([Ca2+]i). 10(-6) M Losartan lacked effects on the [Arg8]vasopressin-induced elevation of [Ca2+]i. In addition, 10(-6) M completely inhibited the angiotensin II-induced stimulation of Na+/H+ exchange in the vascular smooth muscle cells. 10(-10) to 10(-6) M Losartan inhibited the angiotensin II-induced cell protein synthesis in a concentration-dependent manner, yielding to an effective concentration (ED50) of 6.2 +/- 1.8 x 10(-8) M (n = 4). Losartan did not affect the platelet-derived growth factor-BB-induced increase in cell protein. These results show that Losartan is a highly specific angiotensin II receptor antagonist which inhibits angiotensin II-induced cell growth and thus may have beneficial effects on the development and regression of vascular hypertrophy. PMID- 1426031 TI - Fluoxetine modulates G protein alpha s, alpha q, and alpha 12 subunit mRNA expression in rat brain. AB - Signal-transducing G proteins are central to the coordination of receptor effector communication. We have explored the effects of long-term fluoxetine administration of G alpha s, G alpha i1, G alpha i2, G alpha o, G alpha q and G alpha 12 mRNA expression in various rat brain regions using reverse transcriptase polymerase chain reaction (RT-PCR)-mediated cross-species partial cDNA cloning. Northern blot analysis, and RNase protection assay techniques. Fluoxetine decreased G alpha s mRNA in midbrain, while mRNA expression of the novel G protein alpha subunits, G alpha q and G alpha 12, was increased in neostriatum and frontal cortex. We conclude that in addition to post-translational modification, regulation of G protein function by antidepressant drugs may occur at the level of gene expression. PMID- 1426032 TI - Addition of an ER retention signal to the ricin A chain increases the cytotoxicity of the holotoxin. AB - With the exception of diphtheria toxin, which translocates from acidified endosomes, the intracellular organelle from which the catalytic moieties of several plant and bacterial toxins enter the target cell during endocytic uptake has not been identified. We have recently proposed that some toxins may travel the entire secretory pathway in reverse, moving from the cell surface to the lumen of the ER, before entering the cytosol. Several bacterial toxins have the ER retention sequence KDEL or a related analogue at their carboxyl termini, suggesting that the KDEL receptor may play a role in delivering these toxins to the ER. Here we provide further support for this possibility since the cytotoxicity of ricin, which lacks a KDEL sequence, can be significantly increased by adding KDEL to the C-terminus of its A chain. PMID- 1426033 TI - Calpain concentration is elevated although net calcium-dependent proteolysis is suppressed in dystrophin-deficient muscle. AB - The concentration, activity, and distribution of calcium-dependent proteases (calpains) are compared in dystrophin-deficient (mdx) and control mouse muscle. Calpains have been implicated previously as the protease responsible for the observed necrosis in dystrophin-deficient human muscle. Although these mouse and human muscular dystrophies have been attributed to similar genetic defects, the mouse dystrophy shows a brief necrotic episode while the human deficiency results in progressive, lethal muscle necrosis. Findings of the present study show that control mouse muscle contains more calcium-dependent proteolytic activity than dystrophin-deficient muscle. Paradoxically, adult, dystrophin-deficient mouse muscle contains higher concentrations of calpain than found in controls. Furthermore, indirect immunofluorescence using antisera produced against an oligopeptide found in the proteolytic domain of calpain shows that calpain distribution in dystrophin-deficient muscle is dispersed throughout the cytoplasm while immunolabeling of control muscle shows calpain concentrated at Z-discs. This redistribution is consistent with calpain activation in dystrophic muscle. These findings indicate that mdx mice possess the capability of suppressing calpain-mediated proteolysis. We speculate that this suppression may enable dystrophin-deficient mouse muscle to arrest necrosis and regenerate successfully. PMID- 1426035 TI - Revealing nucleolar architecture by low ionic strength treatment. AB - The internal nucleolar architecture of HeLa cells was revealed after a short hypotonic treatment. The response of nucleoli to a gradual reduction in the ionic strength of incubation buffer was assessed by immunofluorescence, confocal microscopy using human autoimmune sera monospecific for antigens present in different nucleolar components, and electron microscopy. The granular component dispersed first, followed by the dense fibrillar component, leaving distinct fibrillar centers remaining. This demonstrates differential sensitivity to low ionic strength treatment in the transcription and the maturation territories of the nucleoli. The changes described develop in only a few minutes and this approach can reveal momentary in situ intranucleolar arrangements. We suggest that the fibrillar centers provide a structural support for RNA-polymerase I complexes and are possibly also attached to a nuclear skeleton. The evidence presented implicates the fibrillar centers as the core elements of nucleoli and that functional nucleoli arise around them. PMID- 1426034 TI - Apical to basolateral surface area ratio and polarity of MDCK cells grown on different supports. AB - We have established conditions under which Madin-Darby canine kidney cells develop a well-polarized monolayer on polycarbonate filters and on transparent filters. These filters have biochemical and mechanical advantages over the nitrocellulose filters which have been widely used. Transepithelial resistance was established 10 h after plating and stabilized after 24 h. The distribution of protein antigens was followed by surface immunofluorescence and quantitated by a surface immunoassay that we developed. Uvomorulin was localized to the lateral membrane, with low amounts detectable on the basal membrane. The 58-kDa antigen was distributed over the entire basolateral domain, including cell processes extending into the filter pores. This distribution was confirmed by immunogold labeling of frozen sections. The 114-kDa antigen was found to be present at similar surface densities on both the apical and the basolateral domain. The support used for growth had profound effects on the cell morphology. A morphometric analysis of the plasma membrane of both strains of the cell line showed an increase in the number and size of the microvilli, and a smoother basal membrane as compared to published data on nitrocellulose filters. The apical to basolateral surface area ratio was therefore modified. PMID- 1426036 TI - Developmental changes in rat liver mitochondrial populations analyzed by flow cytometry. AB - Isolated rat liver mitochondria were split into three density fractions when applied to a Percoll gradient. This phenomenon is observable in the fetus, in the early newborn (1 h), in the suckling newborn (7 days), and in the adult, suggesting that the three density fractions coexist regardless of the state of development. The medium-density fraction sharply decreased immediately after delivery, being replaced by the high-density fraction. Flow cytometry analysis of mitochondrial density fractions stained with rhodamine 123 showed the occurrence in each density fraction and in all developmental states studied of two distinct mitochondrial populations with different fluorescence intensities. Our results suggest that the high-fluorescence population might be an immature form of mitochondria that decreases with the progression of development, coinciding with the postnatal enhancement of mitochondrial respiratory efficiency. PMID- 1426037 TI - PDGF-receptor concentration is elevated in regenerative muscle fibers in dystrophin-deficient muscle. AB - Dystrophin-deficient muscle undergoes sudden, postnatal onset of muscle necrosis that is either progressive, as in Duchenne muscular dystrophy, or successfully arrested and followed by regeneration, as in most muscles of mdx mice. The mechanisms regulating regeneration in mdx muscle are unknown, although the possibility that there is renewed expression of genes regulating embryonic muscle cell proliferation and differentiation may provide testable hypotheses. Here, we examine the possibility that necrotic and regenerating mdx muscles exhibit renewed or increased expression of PDGF-receptors. PDGF-binding to receptors on muscle has been shown previously to be associated with myogenic cell proliferation and delay of muscle differentiation. We find that PDGF-receptors are present in 4-week-old mdx mice in muscles that undergo brief, reversible necrosis (hindlimb muscles) or progressive necrosis (diaphragm), as well as in 4 week-old control mouse muscles. Immunoblots indicate that the concentrations of PDGF-receptors in 4-week-old dystrophic (necrotic) and control muscles are similar. Prenecrotic, dystrophic fibers and control fibers possess some cell surface labeling of fibers treated with anti-PDGF-receptor and viewed by indirect immunofluorescence. Necrotic fibers in dystrophic muscle show cytoplasmic labeling for PDGF-receptors and labeling of perinuclear regions at the muscle cell surface. Adult dystrophic muscle displays higher concentrations of PDGF receptor in both regenerated muscle (hindlimb) and progressively necrotic muscle (diaphragm) than found in controls. Anti-PDGF-receptor labeling of regenerated, dystrophic muscle is observed primarily in granules surrounding central nuclei or surrounding nuclei located at the surface of regenerated fibers. No labeling of perinuclear regions of control muscle or prenecrotic fibers was observed. Myonuclei fractionated from adult mdx hindlimb muscles contained no PDGF receptor, indicating that PDGF-receptor-positive structures are not tightly associated with nuclei or within nuclei. L6 myoblasts show PDGF-receptor distributed diffusely on the cell surface. Stimulation of L6 myoblasts with 10 ng/ml of PDGF-BB causes receptor internalization and concentration in granules at perinuclear regions. Thus, PDGF stimulation of myoblasts causes a redistribution of PDGF-receptors to resemble receptor localization observed during muscle regeneration. These findings implicate PDGF-mediated mechanisms in regeneration of dystrophic muscle. PMID- 1426038 TI - Effect of dexamethasone on proliferating osteoblasts: inhibition of prostaglandin E2 synthesis, DNA synthesis, and alterations in actin cytoskeleton. AB - Elevated levels of glucocorticoids caused by disease (Cushing's syndrome) or therapeutic treatment of asthma are known to cause osteoporosis. Space flight, an environmental condition, is known to cause a rise in endogenous cortisols accompanied by a significant loss of bone and calcium. Long-term space inhabitants have lost up to 18% of weight bearing bone during long-term flight. This study demonstrates that elevated concentrations of glucocorticoids lower the endogenous production of PGE2 and interfere with osteoblast proliferation. Osteoblasts grown with dexamethasone had significantly lower DNA synthesis and endogenous synthesis of PGE2. Addition of exogenous dmPGE2 to the dexamethasone growth-inhibited cells stimulated DNA synthesis over twofold. In synchronous control cultures, we found that endogenous prostaglandin synthesis increased in late G1, preceding S-phase DNA synthesis by several hours. The addition of exogenous dexamethasone to synchronous cultures resulted in a significant decrease in the prostaglandin synthesis followed by a significant decrease in DNA synthesis in parallel cultures. Further, dexamethasone caused the actin cytoskeleton to collapse and the cell morphology to become rounded and spindle shaped. Addition of exogenous PGE2 to the dexamethasone-treated osteoblasts caused recovery of the actin architecture and phenotype. These data support the hypothesis that the glucocorticoid-mediated decrease in prostaglandin synthesis may be a contributing factor in the reduced bone quality and trabecular bone formation seen in glucocorticoid-induced osteoporosis. PMID- 1426039 TI - C32 human melanoma cell endogenous lectins: characterization and implication in vesicle-mediated melanin transfer to keratinocytes. AB - To optimize skin pigmentation in order to help body prevention against UV radiation, the mechanism of melanin pigment transfer from melanocytes to keratinocytes must be elucidated. Melanin transfer to keratinocytes requires specific recognition between keratinocytes and melanocytes or melanosomes. Cell surface sugar-specific receptor (membrane lectin) expression was studied in human C32 melanoma cells, an amelanotic melanoma, by flow cytometry analysis of neoglycoprotein binding as an approach to the molecular specificity. Sugar receptors on melanocytes are mainly specific for alpha-L-fucose. Their expression is enhanced upon treatment by the diacylglycerol analogue 1-oleoyl-2 acetylglycerol, which can induce melanin synthesis in amelanotic human melanoma cells in a dose-dependent manner. Flow cytometry analyses showed a small-sized population of vesicles distinguishable from large cells by their fluorescence properties upon neoglycoprotein binding. Sorting indicated that the small-sized subpopulation is composed of vesicles produced by melanocytic cells. Upon vesicle formation, a selective concentration of sugar receptors specific for 6-phospho beta-D-galactosides appears in the resulting melanocytic vesicles. Vesicles are recognized and taken up by cultured keratinocytes and a partial inhibitory effect was obtained upon cell incubation in the presence of neoglycoproteins, indicating a possible participation of sugar receptors in this recognition. The validity for such a model to help in understanding the natural melanin transfer by melanosomes is confirmed by electron microscopy, which demonstrates the presence of melanin inside keratinocytic cells upon incubation with melanocytic vesicles. PMID- 1426040 TI - Phorbol ester- and calcium-induced reorganization of 180-kDa bullous pemphigoid antigen on the ventral surface of cultured human keratinocytes as studied by immunofluorescence and immunoelectron microscopy. AB - The hemidesmosome is an adhesion structure of the epidermal-dermal junction in keratinocytes. When keratinocytes migrate laterally or upward to differentiate, they must control the formation and disintegration of the hemidesmosomes. When keratinocytes are cultured in low-calcium (below 0.1 mM) medium, all cells behave like basal cells, adhere to the culture dish, and proliferate without differentiation. The calcium addition induces the differentiation. A bullous pemphigoid antigen, 180-kDa BPA, has been shown to be a component of the hemidesmosome. Using a monoclonal antibody to the 180-kDa BPA and a human squamous cell carcinoma cell line (DJM-1 cells), the fate of hemidesmosomes was studied after the addition of calcium to low-calcium-grown cells and 12 tetradecanoylphorbol-13-acetate (TPA) to high-calcium (1.87 mM) grown cells by immunofluorescence and immunoelectron microscopy. The antigen was distributed evenly as fine dots on the entire ventral surface of low-calcium cells, whereas they formed a peculiar, concentric ring or arch arrangement on the ventral surface of high-calcium cells. Immunoelectron microscopy revealed the deposits of gold particles at sites on the membrane surface, where some filamentous or electron-dense materials were associated, although the complete structure of hemidesmosomes was not formed. They deposited directly onto the membrane surface in low-calcium cells and with a distance of 20-50 nm from the membrane surface in high-calcium cells. The calcium addition caused a profound reduction of the 180 kDa BPA-positive area for 30 to 120 min and then formed the high-calcium-ring pattern after 4 to 6 h. A similar calcium response was seen in normal human keratinocytes. TPA (16 nM) treatment caused disintegration of the ring pattern in high-calcium DJM-1 cells. This was inhibited with a protein kinase C (PKC) inhibitor. H7 (20 microM). These results suggest that the hemidesmosome is a dynamic structure and PKC can be one of the major factors in controlling the hemidesmosome, since it is known that the low-high calcium shift induces a calcium influx and a PKC activation, and TPA activates PKC in keratinocytes. PMID- 1426041 TI - Characterization and cellular localization of nucleophosmin/B23 in HeLa cells treated with selected cytotoxic agents (studies of B23-translocation mechanism). AB - Previous studies indicated that nucleophosmin/B23, an abundant nucleolar phosphoprotein, accumulated in the nucleoplasm (B23-translocation) of cells after exposure to selected cytotoxic drugs. Attempts were made to understand the B23 translocation mechanism. This paper reports that: (1) B23-translocation is a reversible process. Upon removal of camptothecin, which induced B23-translocation in HeLa cells, nucleophosmin/B23 relocalized into nucleoli within 2 h. Relocation occurs in the presence of cycloheximide which inhibits new protein synthesis. There is no reduction or degradation of nucleophosmin/B23 detected during drug treatments. Nucleophosmin/B23 has a half-life of 18-20 h. Taken together, these results indicate that B23-translocation is a reversible process. Drug treatment causes redistribution of nucleophosmin/B23 in nucleoplasm. (2) Inhibition of RNA synthesis does not cause the B23-translocation. Over 80% of RNA synthesis was inhibited in HeLa cells by treatment with actinomycin D, camptothecin, and methotrexate. While actinomycin D and camptothecin cause B23-translocation in all cells, 40% of methotrexate-treated cells remain untranslocated. (3) There is no significant change of phosphorylation in nucleophosmin/B23 during drug treatment. An identical oligomeric cross-linkage pattern was obtained in drug-treated cells. (4) HeLa cells treated with B23-translocation effective drugs have small and round nucleoli while control cells have large and irregular-shaped nucleoli. PMID- 1426042 TI - Generation of anti-idiotypic monoclonal antibodies recognizing vasopressin receptors in cultured cells and kidney sections. AB - To produce anti-idiotypic antibodies against receptors for the neurohypophyseal hormone vasopressin, an anti-vasopressin monoclonal antibody with a ligand specificity similar to that of vasopressin receptors was employed for immunization. Three anti-idiotypic monoclonal antibodies were obtained which induced, like vasopressin, plasminogen activator production in the renal epithelial cell line LLC-PK1 (expressing V2-receptors). Induction of plasminogen activator synthesis by the anti-idiotypic antibodies could be inhibited by coincubation with a vasopressin antagonist. In a fashion similar to that of vasopressin itself, the anti-idiotypic antibodies induced receptor down regulation. The anti-idiotypic antibodies were employed to visualize vasopressin receptors on LLC-PK1 and A7r5 (V1-receptor-expressing) smooth muscle cells by immunofluorescence. Antibody-mediated fluorescence was not observed in receptor deficient mutant cell lines or vasopressin-receptor-down-regulated cells. Furthermore, these antibodies were used for immunohistochemical localization of vasopressin receptors in rat and bovine kidney preparations. In accordance with earlier physiological and biochemical observations, vasopressin receptors were detected predominantly in collecting ducts in cortex and medulla. On the cellular level, a differential staining pattern was observed. PMID- 1426043 TI - Spatial rearrangement and enhanced clustering of kinetochores in interphase nuclei of dorsal root ganglion neurons in vitro: association with nucleolar fusion. AB - Interphase nuclei of several cell types display distinct, nonrandom arrangements of specific chromatin domains. It has been suggested that this arrangement is associated with the functional commitment of the cell and results from compartmentalization of specific DNA sequences to transcriptionally competent sites. In a test of the hypothesis that such topological organization is established during cellular differentiation, the spatial distribution of centromeres was determined, in dorsal root ganglion neurons in vitro, using immunocytochemistry in conjunction with fluorescence microscopy, confocal laser microscopy, and ultrastructural immunogold techniques. Kinetochores occurred as clusters, in association with nucleoli and with the nuclear envelope. Neurons at different stages of differentiation, as determined by nucleolar distribution, exhibited a distinct, stage-specific, spatial organization of kinetochores. Morphometric analyses, together with serial reconstruction, indicated that progressive clustering of kinetochores accompanies differentiation and that such clustering occurs in association with nucleolar fusion. The data presented indicate that the chromatin organization observed in the fully differentiated state may be the result of controlled rearrangements of specific chromatin domains during differentiation and that the mechanism governing such rearrangement and the process of cellular differentiation may be linked. PMID- 1426044 TI - Polarized secretion of urokinase-type plasminogen activator by epithelial cells. AB - Numerous epithelial cell types produce and secrete plasminogen activators (PAs) and/or PA inhibitors (PAIs). When epithelial cells were grown on polycarbonate filters and their apical and basolateral secretion products analyzed, PA activity accumulated in a highly polarized fashion; depending upon the cell line, the compartment of PA accumulation was either apical (MDCK I cells and HBL-100 cells) or basolateral (LLC-PK1, CaCo-2, and HeLa cells). By contrast, PAI-1 was recovered in roughly equal amounts in both compartments. Basolateral accumulation of urokinase-type plasminogen activator (uPA), but not its apical targeting, required an acidic compartment and the integrity of the cytoskeleton. Polarity of uPA accumulation did not result from removal of the free enzyme from the opposite compartment through its binding to the cell surface. Transfection with wild-type or mutated murine uPA demonstrated that neither the "growth factor" domain nor the kringle domain is required for the appropriate sorting of the protein. We propose that polarized secretion of PAs is one mechanism whereby cells spatially control extracellular proteolysis. PMID- 1426046 TI - Minipodia, novel structures for extension of the lamella: a high-spatial resolution video microscopic study. AB - Extension of leading lamellae has been analyzed by high-spatial- and -time resolution video microscopy. Many tiny semicircular profiles, hereby named minipodia, have been found at the leading edge of locomoting fibroblasts in culture. These new structures are not "miniruffles" since minipodia seem to originate underneath the leading lamella. Once initiated, minipodia quickly expand and become indistinguishable from what have been known as lamellipodia. The minipodial front becomes the new focal leading edge. So, it appears that leading lamellae do not extend directly themselves, but minipodia protrude underneath them to become new leading edges. These findings are not compatible with the current concept of cell movement, and a new model is proposed. PMID- 1426045 TI - Resistance to 1,25-dihydroxyvitamin D3 of a deoxycytidine kinase-deficient variant of human leukemia HL60 cells. AB - A deoxycytidine kinase-deficient variant of HL60 cells (HL60-araC), isolated by its resistance to 1-beta-D-arabinofuranosyl cytosine (ara-C), shows cross resistance to the differentiation-inducing and growth-inhibitory effects of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3). This is not due to the lack of uptake of 1,25(OH)2D3 by HL60-araC cells, shown by an increased rate of intracellular accumulation of [3H]-1,25(OH)2D3, or to the lack of expression of the gene for the vitamin D3 receptor. However, down-modulation of the expression of this gene by 1,25(OH)2D3 is markedly delayed in HL60-araC cells, and the down-regulation of the expression of the c-myc gene is also delayed. In contrast, the expression of the constitutively expressed 16S mitochondrial rRNA gene is unchanged by 1,25(OH)2D3 treatment of either cell subline. These findings suggest that some cases of drug resistance may be associated with defective functioning of a differentiation pathway. PMID- 1426047 TI - Identification and characterization of a novel high-molecular-weight form of the integrin alpha 3 subunit. AB - The integrin alpha 3 beta 1 is a multiligand extracellular matrix receptor found on many cell types. Immunoprecipitations of 125I-surface-labeled prostate carcinoma cell lines, DU145 and PC-3, with the anti-alpha 3 integrin monoclonal antibodies J143 or PIB5, resulted in the coimmunoprecipitation, along with the expected alpha 3 beta 1 heterodimer, of a polypeptide with a molecular mass of 225 kDa. This protein could also be copurified with the 155-kDa alpha 3 and 115 kDa beta 1 subunits upon affinity chromatography of 125I-surface-labeled cell extracts on anti-alpha 3 antibody-Sepharose columns. Upon reduction, this 225-kDa protein generated 130- and 95-kDa polypeptides, while the 155-kDa alpha 3 subunit generated 130- and 25-kDa polypeptides. The 225-kDa protein did not generate a 25 kDa polypeptide. Deglycosylation and reduction of the 225-kDa protein resulted in the generation of 110- and 95-kDa polypeptides, while deglycosylation and reduction of the 155-kDa alpha 3 resulted in a 110-kDa polypeptide identical in size to the 110-kDa polypeptide generated from the 225-kDa protein. Peptide maps generated from the 110-kDa components of the 225-kDa polypeptide and the 155-kDa alpha 3 integrin subunit were identical, as were their N-terminal amino acid sequences. An antibody directed against the cytoplasmic domain of the alpha 3 subunit immunoprecipitated the 225-kDa polypeptide in addition to the 155-kDa alpha 3 subunit. Furthermore, Northern blot analysis of RNA from DU145 and PC-3 cells with a human alpha 3 cDNA probe identified an mRNA species of 6.2 kb in addition to a major mRNA species of 4.3 kb. The larger mRNA species, which is of an appropriate size for encoding a polypeptide of approximately 220-kDa, was not detectable in cells which did not express the 225-kDa protein. These data demonstrate that the 225-kDa polypeptide represents a novel integrin alpha 3 subunit consisting of the alpha 3 integrin heavy chain disulfide-bonded to a 95 kDa polypeptide which may represent an alternative "light" chain to the 25-kDa light chain of the alpha 3 subunit. PMID- 1426048 TI - 3T3 cell surface galactosyltransferase is a calcium-dependent adhesion molecule for collagen type IV. AB - Cell surface galactosyltransferase (GalTase) has been previously shown to mediate cell spreading or migration on laminin matrices. This work demonstrates that 3T3 cell surface GalTase also mediates cell attachment to collagen type IV. Attachment to collagen type IV was blocked by perturbations of GalTase or substrate pregalactosylation on cells possessing only calcium-dependent mechanisms of adhesion. Cells with both calcium-dependent and calcium-independent systems were not affected by GalTase perturbation. Collagen type IV was shown to possess GalTase substrates since matrices could be galactosylated by both soluble enzyme and 3T3 cells. PMID- 1426049 TI - The E1a gene prevents inhibition of keratinocyte proliferation by dexamethasone. AB - Glucocorticoids have inhibitory effects on the proliferation of several cell types. In this study, we found that dexamethasone, a synthetic steroid with glucocorticoid activity, inhibits proliferation of established mouse Pam 212 keratinocytes. Transfection with the adenoviral early region 1a (E1a) gene confers a strong resistance to the inhibition by dexamethasone. Two deletion E1a mutants, one whose product lacks the ability to bind the cellular proteins p60/p105/p107 and another that is unable to bind p300, were shown to induce a resistance similar to that associated with the intact E1a gene. These results differ from those previously observed with two other growth inhibitory signals, transforming growth factor beta 1 and adenosine 3',5'-cyclic monophosphate, in which the mutated E1a genes confer only partial or no resistance, indicating that a different mechanism mediates resistance against glucocorticoids. PMID- 1426050 TI - Basal lamina formation by epithelial cell lines correlates with laminin A chain synthesis and secretion. AB - Laminin is a major component of the basal lamina upon which all epithelial cells reside in vivo. The synthesis of basal lamina components and their subsequent assembly into a morphologically distinct basal lamina is a differentiated function of epithelial cells in vivo. Ultrastructural studies in our laboratory show that some epithelial cell lines (P-MDCK) form a basal lamina when cultured on membrane-permeable substrate (Millipore Millicells or type I collagen gels). Under the same conditions other epithelial cell lines (MDCK-AA7, M-mTAL-1P, and T84) do not form a basal lamina. When metabolically labeled with [35S]methionine, laminin A and B chains can be immunoprecipitated from the culture medium and culture lysates of P-MDCK cells. In contrast, labeled laminin chains cannot be immunoprecipitated from the culture medium of MDCK-AA7, M-mTAL-1P, and T84 cells. Immunoprecipitates of MDCK-AA7, M-mTAL-1P, and T84 culture lysates demonstrate the presence of one or both B chains but not A chains. These results suggest that laminin B chain synthesis is constitutive in MDCK-AA7, M-mTAL-1P, and T84 cells and that B chains, in the absence of A chains, are not secreted. Furthermore, laminin secretion and basal lamina formation are not required to maintain structural and functional polarity in these cell lines. PMID- 1426051 TI - A comparison of the intracellular distribution of mu-calpain, m-calpain, and calpastatin in proliferating human A431 cells. AB - Little is known about the relative intracellular localizations of the calcium dependent proteases, calpains, and their naturally occurring inhibitor, calpastatin. In the present study, the intracellular localization of mu-calpain, m-calpain, and calpastatin was studied at the light microscopic level in proliferating A431 cells. Highly specific antibodies against the three antigens revealed distinct staining patterns in interphase and mitotic cells. Most notably, calpastatin in interphase cells was localized near the nucleus in tube like, or large granular structures, while the calpains were more uniformly distributed through the cytoplasm in either a fibrillar form (mu-calpain) or a diffuse or fine granular form (m-calpain). The distribution patterns of the two calpain isozymes were distinctly different during mitosis. m-Calpain was concentrated at the mitotic spindle poles and midbody, while mu-calpain appeared to accumulate at the cell membrane and the spindles. Four other human cell lines as well as normal human monocytes were examined to determine if the calpains calpastatin segregation patterns are common to other cells or are unique to the A431 line. With the exception of abundant nuclear mu-calpain in the C-33A cervical carcinoma, the segregation of the proteins was similar to that of A431. These studies indicate that calpains may be localized at regions which are relatively poor in calpastatin content. Proteins at these sites may be susceptible to calpain-catalyzed cleavage. PMID- 1426052 TI - Flow cytometric detection of transforming growth factor-beta expression in rabbit articular chondrocytes (RAC) in culture--association with S-phase traverse. AB - We have previously shown that TGF-beta 1 decreased the entry of G0/G1 synchronized rabbit articular chondrocytes (RAC) into S-phase, whereas it enhanced the proliferation rate of actively dividing cells (asynchronous or S phase-synchronized cells). The growth proliferative effect was accompanied by both increased DNA replication rate and G2/M delay. Since TGF-beta mRNA has been detected in chondrocytes, it was of interest to study the expression of the factor in correlation with the cell cycle of RAC. Using cytofluorometric analysis of both DNA content and TGF-beta protein level, we demonstrated that S-phase synchronized RAC constitutively expressed TGF-beta, whereas G0/G1-synchronized cells only display very low levels of the factor. The data showed that the expression of TGF-beta is correlated with S-phase traverse since it increases with the percentage of cells in S-phase (less than 27% in G0/G1 to 70% in S-phase synchronized cells). Moreover, exposure of RAC to TGF-beta 1 (1 ng/ml) for 24 h increased the percentage of positive cells, independently of the number of cells in S-phase, indicating that the factor may up-regulate its own expression. All together, these data suggest that TGF-beta could play a role in initiating the proliferation of articular chondrocytes during the early events of osteoarthritis and might take a part in the repair of cartilage matrix. PMID- 1426053 TI - Hyaluronate binding and CD44 expression in human glioblastoma cells and astrocytes. AB - CD44 is an integral membrane glycoprotein of approximately 90 kDa which has been implicated in the binding of hyaluronate to the cell surface. The expression of CD44 in astrocytes was investigated by means of indirect immunofluorescence on cultured cells. The vast majority of these cells were found to express CD44. Western blot analysis of these cells revealed a highly polydisperse species having an M(r) corresponding to 74-86 kDa. In order to visualize hyaluronate binding cells, living cultures were probed with fluorescein-conjugated hyaluronate (FI-HA). Some astrocytes were able to bind FI-HA, provided that they were first treated with hyaluronidase. Streptomyces hyaluronidase, which is hyaluronate-specific, was effective in exposing the hyaluronate-binding capacity of these cells. This leads one to conclude that hyaluronate is bound to the surface of these cells and that it masks their capacity to bind hyaluronate. Provided that they were first treated with hyaluronidase, the U-87 MG (glioblastoma-astrocytoma), U-373 MG (glioblastoma), and Hs 683 (glioma) cell lines were also able to bind FI-HA. The U-138 MG (glioblastoma) cell line was unable to bind FI-HA, with or without prior hyaluronidase treatment. A quantitative assay was developed with the use of [3H]hyaluronate ([3H]HA). This revealed the binding to be highly specific, inasmuch as the addition of unlabeled hyaluronate, but not other glycosaminoglycans, was effective in inhibiting the binding of the [3H]HA. An anti-CD44 monoclonal antibody, 50B4, was able to inhibit the binding of the [3H]HA to the U-373 MG cell line. In this cell line, then, CD44 functions as a hyaluronate receptor and one may infer that this is also the case in some astrocytes. PMID- 1426054 TI - BEN, a novel surface molecule of the immunoglobulin superfamily on avian hemopoietic progenitor cells shared with neural cells. AB - BEN is a novel molecule of the immunoglobulin superfamily that we previously identified by means of a monoclonal antibody on neural cell populations during avian development and epithelial cells of the bursa of Fabricius. In this paper, we describe the expression of BEN by hemopoietic cells during ontogeny. In the thymus, BEN is expressed as early as E9, and from E12 until just after hatching 30-60% of thymocytes are BEN positive. Thus the cells expressing BEN are immature thymocytes and not yet differentiated T cells. In the spleen, BEN expression parallels the myelopoietic activity. It is present on 75% of splenocytes during embryonic development and falls rapidly to 20% of cells during the first week after hatching when the spleen is becoming a secondary lymphoid organ. BEN is also found on a large proportion (about 80% positive cells) of bone marrow cells during ontogeny. Post hatching, BEN is present on 40-50% of bone marrow cells. The population of BEN-positive cells in the bone marrow includes myeloid and erythroid progenitor cells, identified by their ability to form colonies in vitro. BEN expression is lost as progenitor cells proliferate and differentiate to develop mature colonies in the clonal assay. Mature myeloid cells, such as macrophages, granulocytes, thrombocytes, and erythrocytes do not express the BEN antigen. Taken together, these data demonstrated that BEN is a stage-specific rather than a lineage-specific differentiation antigen expressed by immature hemopoietic cells. PMID- 1426055 TI - The effects of near-UV radiation on elasmobranch lens cytoskeletal actin. AB - The role of near-UV radiation as a cytoskeletal actin-damaging agent was investigated. Two procedures were used to analyse fresh smooth dogfish (Mustelus canis) eye lenses that were incubated for up to 22 hr in vitro, with elasmobranch Ringer's medium, and with or without exposure to a near-UV lamp (emission principally at 365 nm; irradiance of 2.5 mW cm-2). These were observed histologically using phalloidin-rhodamine specific staining and by transmission electron microscopy. In addition, solutions of purified polymerized rabbit muscle actin were exposed to the same UV conditions and depolymerization was assayed by ultracentrifugation and high-pressure liquid chromatography. While the two actins studied do differ very slightly in some amino acid sequences, they would react physically nearly identically. The results showed that dogfish lenses developed superficial opacities due to near-UV exposure. Whole mounts of lens epithelium exhibited breakdown of actin filaments in the basal region of the cells within 18 hr of UV exposure. TEM confirmed the breakdown of actin filaments due to UV exposure. SDS-PAGE and immunoblotting positively identified actin in these cells. Direct exposure of purified polymerized muscle actin in polymerizing buffer led to an increase in actin monomer of approximately 25% in the UV-exposed solutions within 3-18 hr, whether assayed by ultracentrifugation or HPLC. The above indicates that elasmobranch lens epithelial cells contain UV-labile actin filaments, and that near-UV radiation, as is present in the sunlit environment, can break down the actin structure in these cells. Furthermore, breakdown of purified polymerized muscle actin does occur due to near-UV light exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426056 TI - Subcellular localization of bFGF in human retinal pigment epithelium in vitro. AB - Basic fibroblast growth factor is a polypeptide mitogen with potential biological roles in angiogenesis, differentiation, and the survival of neurons. To study the expression and subcellular distribution of basic fibroblast growth factor in human retinal pigment epithelium in vitro, affinity-purified antipeptide antibodies were generated against a 15 amino acid sequence in the amino-terminus of this growth factor. Analysis of the cross reactivity and specificity of the affinity-purified antibodies demonstrated no ability to recognize acidic fibroblast growth factor and the ability to label specifically the major known forms of basic fibroblast growth factor in whole-cell lysates of retinal pigment epithelium in vitro. Examination of paraformaldehyde- or glutaraldehyde-fixed pigment epithelium at the light and electron microscopic levels revealed prominent localization of basic fibroblast growth factor to the nucleus and nucleolus. In cells fixed with organic reagents, prominent cytoplasmic staining was noted in addition to the nuclear staining seen in aldehyde fixed cells. Investigation of subcellular fractions by Western blot analysis indicated cytosolic as well as nuclear localization of the basic fibroblast growth factor. These analyses, however, demonstrated that the higher molecular weight forms of basic fibroblast growth factor predominate in the nucleus. PMID- 1426057 TI - Ion concentrations, fluxes and electrical properties of the embryonic chicken lens. AB - The membrane properties of embryonic chicken lenses were characterized using isotopic and electrical techniques. The lenses had a relatively high water content (80%) and large extracellular space (12.5%). Isotopic uptake measurements indicated that the lens cytoplasm contained 118 mM K+ and 26 mM Cl-. A value for intracellular Na+ of 14 mM was obtained using Na(+)-sensitive microelectrodes. A double-exponential model was used to fit the efflux of 86Rb+, 22Na+, 36Cl- and [3H]mannitol (an extracellular space marker) from the lens. When perfused with artificial aqueous humor (AAH) solution, embryonic lenses exhibited membrane potentials of between -20 and -40 mV. The more negative values were generally observed in lenses from older embryos. A ouabain-sensitive component, contributing -7 mV to the membrane potential, was also identified. The relatively depolarized membrane potentials suggested that the lens membranes were only weakly selective for K+ over Na+. To test this further, lenses were perfused with AAH containing varying concentrations of K+. The resulting changes in potential were interpreted in terms of the Goldman model. The best fit of the Goldman potential equation indicated that, in the presence of ouabain, the chicken lens membranes had a relative permeability to K+, Na+ and Cl- of 1.0, 0.36, 0.51 respectively. Replacing most or all of the Na+ in the AAH caused only a small change in the membrane potential rather than the large hyperpolarization towards the K+ equilibrium potential predicted by the Goldman model. Including the K+ ionophore valinomycin in the low Na(+)-AAH solutions caused a large increase in 86Rb+ efflux but did not result in additional hyperpolarization. This suggested that the insensitivity of the membrane potential to reduced extracellular Na+ was not due to voltage or pH inactivation of lens K+ channels. PMID- 1426058 TI - Photoreceptor-specific activity of the human interphotoreceptor retinoid-binding protein (IRBP) promoter in transgenic mice. AB - In order to define the cellular specificity of the interphotoreceptor retinoid binding protein (IRBP) promoter in the retina, we linked the human IRBP promoter to the beta-galactosidase (lacZ) gene and made five lines of transgenic mice. In three of the five transgenic mouse lines, retinas showed positive staining upon incubation with 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-gal). Mice from one line (OVE278B) showed positive X-gal staining throughout the retina except for the most peripheral regions. Interestingly, the staining was heterogeneous throughout the retina. Heavily stained regions were interspersed with lightly stained areas. Mice in two other lines showed highly mosaic X-gal staining patterns. Histological examination demonstrated that staining was confined to photoreceptor cells in all three expressing families. Furthermore, electron microscopy showed that the promoter is active in both rod and cone cells. Our results demonstrate that the human IRBP promoter can be used to obtain photoreceptor-specific gene expression in transgenic mice. PMID- 1426059 TI - Metabolism of arachidonic acid by isolated rabbit ciliary epithelium. AB - We examined the ability of rabbit ciliary epithelium to metabolize arachidonic acid in vitro. The epithelium was homogenized and incubated with 14C-labeled arachidonic acid. 14C-labeled metabolites were extracted and then separated by thin layer chromatography. The range of arachidonic acid metabolites synthesized by ciliary epithelium was compared to the metabolites generated by rabbit iris ciliary body. Ciliary epithelium produced substantial amounts of arachidonic acid metabolites that comigrated with 5-HETE and 12-HETE. Authenticity of the 12-HETE produced by ciliary epithelium was confirmed by gas chromatography/mass spectrometry. The ciliary epithelium generated only small amounts of the cyclooxygenase products, PGF2 alpha, PGE2, PGD2 and 6k-PGF1 alpha. In contrast, the iris-ciliary body produced large amounts of cyclooxygenase products such as PGF2 alpha and PGD2. The ability of the ciliary epithelium to generate 12-HETE is noteworthy since 12(R)-HETE is known to be capable of lowering intraocular pressure. PMID- 1426060 TI - Transdifferentiation of chicken retinal pigmented epithelial cells in serum-free culture. AB - A serum-free culture of chicken retinal pigmented epithelial cells has been established in order to analyse how cell-substrate interactions or environmental factors affect the process of transdifferentiation into lens cells from pigmented epithelial cells. The serum-free culture medium for chicken pigmented epithelial cells was Eagle's minimum essential medium, supplemented with chicken transferrin, soybean trypsin inhibitor and bovine insulin. Pigmented epithelial cells were able to survive and grow in the medium for longer than 2 weeks. Collagen did not promote initial cell attachment, but this material effectively supports pigmented epithelial cells to organize monolayer structure characteristics to pigmented epithelium in situ in comparison with the plastic substrate of culture dishes. The process of lens transdifferentiation of chicken pigmented epithelial cells in serum-free conditions was also enhanced with the aid of phenylthiourea and testicular hyaluronidase, which had already been known to promote the transdifferentiation of pigmented epithelial cells in the serum supplemented condition. Typical lentoid bodies were developed after about 2 weeks of serum-free culture. Thus, we can clearly demonstrate that the chicken embryonic pigmented epithelial cells do not always require a full set of serum factors for their transdifferentiation to lens cells in vitro. PMID- 1426061 TI - Effects of intraocular pressure on pH outside rod photoreceptors in the cat retina. AB - Double-barreled H(+)-selective microelectrodes were used to study the effect of raising intraocular pressure (ocular hypertension) on intraretinal pH in the cat. A surprising alkalinizing response was observed in the subretinal space on the first experimental day in seven of 11 experiments. Of the three retinal regions studied, the alkalinizing response was present in the area centralis and in the adjoining near-discal region, but was absent in the superior temporal periphery. The alkalinizing response was relatively fragile, diminishing and then extinguishing with repetition of episodes of ocular hypertension. It was also never observed on the second experimental day. The alkalinizing response had a relatively low threshold, appearing with 10 mmHg elevations of intraocular pressure, i.e. when the perfusion pressure was still relatively high, but was also present across a wide range of perfusion pressures. It was maximal in amplitude in the most distal portion of the subretinal space and consisted of two components, an 'on' alkalinization during the episode of ocular hypertension, and an 'off' alkalinization following it. When the alkalinizing response was present in the subretinal space, it also could be recorded with placement of the microelectrode in the choroid. Elevations of systemic arterial blood pressure with epinephrine (intravenous), by raising perfusion pressure, also alkalinized the subretinal space, indicating that an increase in choroidal blood flow can produce this type of pH response. While pH recordings do not directly monitor blood flow, we tentatively interpreted the alkalinizing response with ocular hypertension as originating from a regional increase in choroidal blood flow, but we cannot rule out other explanations. Acidification of the subretinal space in response to ocular hypertension replaced the alkalinizing response when the latter extinguished, or acidification was the sole response in the absence of an alkalinization. The acidification also had a low threshold, was maximal in the most distal portion of the subretinal space, and increased in size with decreases in perfusion pressure. The acidification was reduced in amplitude by breathing 100% oxygen (hyperoxia). This was interpreted as suppression of the component of acidification that originated from an increase in glycolysis by the rod photoreceptors during ocular hypertension. PMID- 1426063 TI - Growth-associated protein GAP-43 and nerve cell adhesion molecule in sensory nerves of cornea. AB - We used dual-wavelength fluorescence microscopy and monoclonal antibodies to growth-associated protein (GAP-43) and nerve cell adhesion molecule (N-CAM) to identify these proteins in nerve fibers of normal rat and rabbit corneas. Overlapping immunoreactivity of GAP-43 and N-CAM was evident along nerve fibers of rabbit corneal sections, suggesting that GAP-43 is constitutively expressed in these sensory nerves. The immune reaction of monoclonal antibody to GAP-43 and [125I]protein A was used to quantitate relative amounts of GAP-43 in the normal cornea and in a cornea subjected to a de-epithelializing wound. Collectively these findings imply that GAP-43 is axoplasmically transported from cells in the trigeminal (or superior cervical) ganglion to the cornea. Moreover, these data indicate that GAP-43 appears to be involved in the remodeling of corneal nerves that is necessary for normal innervation. PMID- 1426062 TI - Characterization of the interphotoreceptor matrix surrounding rod photoreceptors in the human retina. AB - Previous studies have documented the presence of specific lectin-binding domains in the insoluble interphotoreceptor matrix (IPM) isolated from human retina. Peanut agglutinin (PNA) selectively binds to cone matrix domains whereas wheat germ agglutinin (WGA) binds to matrix domains surrounding rods. In the present study, the rod-associated WGA-binding domains are further characterized using lectin-based cytochemistry and polyacrylamide gel electrophoresis in combination with neuraminidase digestion. The lectin-binding patterns of non-neuraminidase treated samples are similar to those described in previous reports. After neuraminidase treatment, both rod and cone matrix domains demonstrate PNA binding while the binding of WGA to rod matrix domains is reduced. However, the binding of WGA to photoreceptor outer segments is not affected by neuraminidase. Blots of IPM proteins probed with lectins indicate that the WGA-binding macromolecules are represented as a group of high molecular weight glycoproteins, whereas the PNA binding components are represented as a group of lower molecular weight glycoproteins. The major WGA-binding glycoprotein (147 kDa) shows reduced binding affinity to WGA and increased binding affinity to PNA following neuraminidase treatment. Further, this 147-kDa glycoprotein, although similar in molecular weight to IRBP (interphotoreceptor retinol-binding protein) (141 kDa), is not recognized by the lectin, concanavalin A (Con A), or by an anti-IRBP antibody. Our data suggest that: (1) the major component of the WGA-binding domain demonstrated by polyacrylamide gel analysis is a glycoprotein with a molecular weight of 147 kDa containing galactose residues that are masked by terminal sialic acid residues; and (2) the binding of WGA to photoreceptor outer segments is resistant to neuraminidase, consistent with the earlier reports that WGA binding domains of photoreceptor outer segments may not be sialyl-containing glycoconjugates. PMID- 1426064 TI - Immunohistochemical characterization of dendritic cells and macrophages in the aqueous outflow pathways of the rat eye. AB - Immunohistochemical studies were performed to determine the distribution, phenotype and ontogeny of macrophages and dendritic cells (DCs) in the aqueous humour outflow pathways of the rat eye. Optimal fixation and indirect immunoperoxidase techniques were employed in conjunction with a panel of mAbs on tangential frozen sections of ocular tissues from a total of 37 Wistar Furth rats aged 12-13 days (n = 8), 3 weeks (n = 12), 7 weeks (n = 5) and 15 weeks (n = 12). The density of immunopositive cells was scored qualitatively. A moderate to low density of Ia+ cells with a dendritic morphology were observed in the trabecular meshwork. DCs were also identified in the suprachoroidal space and in the connective tissues of nerves and vessels piercing the sclera, i.e. in association with non-conventional aqueous outflow pathways. The phenotypical and morphological characteristics of these cells would indicate that they may potentially act as antigen presenting cells (APCs). Non-dendritic pleomorphic cells with a macrophage phenotype were also identified in the trabecular meshwork, and bipolar or elongated cells with a macrophage phenotype were a noticeable feature in the perivascular region of collector channels and the limbal episcleral veins. Some macrophage and DC-like cells were observed in intimate association with limbal mast cells. Theories on the mechanisms of Anterior Chamber Associated Immune Deviation (ACAID) have assumed APCs are largely absent from the tissues lining the anterior chamber. Our findings of a low but moderate density of putative APCs in the conventional and non conventional aqueous humour outflow pathways are discussed in relation to the various theories of ACAID. PMID- 1426065 TI - Expression of interleukin-1 alpha, interleukin-1 beta, and an interleukin-1 receptor antagonist in human retinal pigment epithelial cells. AB - mRNA expression and protein production of interleukin-1 alpha, interleukin-1 beta and intracellular and secreted forms of an interleukin-1 receptor antagonist were measured in visually confluent monolayers of unstimulated cultured human retinal pigment epithelial cells and after cells were stimulated with recombinant cytokines. Using reverse transcription polymerase chain reaction, transcripts for interleukin-1 alpha and interleukin-1 beta were not detected in unstimulated cells from any of six donors whereas mRNA expression for both interleukin-1 alpha and interleukin-1 beta was readily induced in all six cell lines after cells were stimulated with recombinant IL-1 (alpha or beta), tumor necrosis factor alpha, or lipopolysaccharide. The combination of cycloheximide and recombinant interleukin 1 caused a 14-fold enhancement of interleukin-1 alpha and interleukin-1 beta mRNA expression above that observed after cells were stimulated with interleukin-1 alone. After stimulation by interleukin-1, cells produced intracellular interleukin-1 alpha protein, but did not secrete it into medium. In contrast, interleukin-1 beta protein was not detected in cell lysates or conditioned-medium after stimulation with interleukin-1. An intracellular interleukin-1 receptor antagonist was expressed constitutively by human retinal pigment epithelial cells; mRNA transcripts were enhanced in a dose and time dependent manner after cells were exposed to recombinant interleukin-1 or tumor necrosis factor alpha. In contrast, mRNA for a secreted form of the interleukin-1 receptor antagonist was not detected under basal conditions or after cells were stimulated by recombinant cytokines. Interleukin-1 receptor antagonist protein was found primarily in cell lysates; little interleukin-1 receptor antagonist protein was secreted by the cells. The presence of cell-associated interleukin-1 receptor antagonist was confirmed by immunocytochemistry. Levels of cell-associated IL-1 receptor antagonist protein were not significantly influenced by recombinant interleukin-1 or tumor necrosis factor alpha. Endogenous expression of interleukin-1 receptor antagonist may attenuate the effect of exogenous or endogenous interleukin-1, thus providing the RPE cell a means of maintaining interleukin-1 homeostasis in ocular inflammatory disease. PMID- 1426066 TI - Decreased ascorbic acid entry into cornea of streptozotocin-diabetic rats and guinea-pigs. AB - High L-ascorbic acid (AA) levels in aqueous humor and intraocular tissues including lens and cornea are thought to protect against the harmful effects of the photochemical and ambient oxidation reactions involving oxygen and its radicals. Our pulse-chase studies follow a bolus of radiolabeled test molecules including [14C]L-ascorbic acid and [3H]L-glucose (L-glu) introduced into the blood at time t = 0, and determine the time-dependent concentrations of these labeled molecules as they move into aqueous humor, corneal endothelium and stroma tissues. Calculated entry and exit rate constants provide a representative measure of the functional state of passive and carrier mediated transport mechanisms in situ in normal and diabetic animals. Diabetic rats were categorized in terms of length of time exposed to a uniform, monitored streptozotocin (stz) diabetes as: short term (10-20 days); mid-term (40-60 days); and long term (100+ days). In the rat, we observed little change in entry rate of L-glu (a passive marker) into aqueous humor [control Ki = 0.0216 +/- 0.0021 (n = 14)/mid-term stz diabetes Ki = 0.0202 +/- 0.0027 (n = 10)] and a modest decrease in the entry rate of AA into aqueous humor [control KAi = 0.0231 +/- 0.0022 (n = 14)/mid-term stz diabetes KAi = 0.0201 +/- 0.0034 (n = 10)]. At corneal endothelium, we noted a significant decrease in the active movement of AA [control KE = 0.614 +/- 0.053 (n = 14)/mid-term stz-diabetes KE = 0.220 +/- 0.026 (n = 9)] while the passive L glu entry rate remained essentially unchanged.+ PMID- 1426067 TI - Proteoglycans in the mouse interphotoreceptor matrix. VI. Evidence for photoreceptor synthesis of chondroitin sulfate proteoglycan using genetically fractionated retinas. AB - To determine the role of photoreceptors in the synthesis of chondroitin sulfate proteoglycan (CS-PG) present in the interphotoreceptor matrix (IPM), 35SO4(2-) was used as a tracer for comparison of proteoglycans synthesized in vitro in the absence of the pigment epithelium by normal retinas and retinas from retinal degeneration (rd) mice at stages before and after photoreceptor degeneration. Isolated retinas from 10 day post-partum (P-10) pups, adult normal mice (C57BL/6J ++/++) and retinal degeneration mice (C57BL/6J rdle/rdle) were incubated for 7 hr with 35SO4(2-) to label newly synthesized sulfated proteoglycans. At P-10, rd retinas have not undergone extensive photoreceptor degeneration, whereas in the adult retinas from this strain, only a few cone photoreceptors remain. At the termination of the labeling period, proteoglycans in the incubation medium and those remaining in guanidine hydrochloride (GuHCl) extracts of the retina were analysed separately and identified by their susceptibility to enzymatic or nitrous acid depolymerization. At P-10, no significant differences were observed in the types or sizes of newly synthesized proteoglycan in normal and rd retinas. Medium samples from P-10 retinas contained near equal amounts of 35S-labeled CS PG and heparan sulfate proteoglycan (HS-PG), while in GuHCl extracts, approximately 90% of the 35SO4(2-) was incorporated into HS-PG, with the remainder found in CS-PG. Comparisons of adult tissue revealed a divergence of proteoglycan synthesis profiles. Retinas from normal adults label predominantly CS-PG. [35S]proteoglycan from normal retina incubation medium was approximately 96% CS-PG, and GuHCl extracts were about 73% CS-PG. From adult rd retinas these values were 18 and 10%, respectively. Per retina, this shows the rd retinas labeling less than 4% of the medium CS-PG, and about 50% of the GuHCl extractable CS-PG compared to normal retinas. Labeled HS-PG comprised about 28% of the normal retina GuHCl extracts, but was not detected in the incubation medium. In contrast, HS-PG synthesis accounted for about 76% of the medium proteoglycan label, and about 85% of the extracted proteoglycan in the adult rd retina. In fact, 35SO4(2-) labeling of HS-PG in the rd retina GuHCl extracts exceeded by 1000% the level observed in normal retina extracts on a per retina basis. Retinas from both strains incorporate significant amounts of 35SO4(2-) into proteins with rd achieving higher specific activity. IRBP was identified as a 35SO4(2-) labeled protein by immunoadsorption from aliquots of the incubation medium.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1426068 TI - Lens structures exist transiently in development of transgenic mice carrying an alpha-crystallin-diphtheria toxin hybrid gene. AB - The development of lens structures in transgenic mice (lnl mice) which carry the diphtheria toxin A chain-coding sequence under the control of the alpha crystallin promoter is examined here in detail. The initial stages of lens development during embryonic days 10.5 to 12.5 (E10.5-E12.5), including the invagination of the surface ectoderm to form a lens vesicle, closure of the vesicle to form a lens cup, and initial appearance of the lens itself, appeared identical in histologic analyses of lnl mice and genotypically wild-type littermate controls. However, by E12.5, cells in the central posterior lens of developing lnl mice appeared to be vacuolated and undergoing necrosis. This necrosis was quite prominent at E14.5 and the overall lens size was significantly reduced. The lenses of lnl mice continued to be present but were significantly smaller throughout embryonic development. The cells of these lenses were capable of undergoing biochemical differentiation, reacting with antibodies to both alpha and beta-/gamma-crystallin. alpha-Crystallin expression was initiated at the appropriate time (E10.5) and maintained in most cells of lnl lenses. The expression of beta-/gamma-crystallins was surprising as these crystallins are expressed later in lens development after normal expression of alpha-crystallin and after the anticipated time of expression of the diphtheria toxin transgene. Despite extensive necrosis and cell death, lens structures persisted in lnl mice and disappeared only in the early postnatal period between days 3 and 6. Throughout the perinatal period, the remaining lens cells expressed both alpha- and beta-/gamma-crystallins. Prenatal development of the retina and ciliary body was relatively normal although the eye was significantly reduced in overall size. Some additional developmental defects were noted including persistent hyaloid artery and thickened cornea. In the perinatal period the rapidly expanding retina filled the entire eye leaving essentially no anterior or posterior chamber. These results clearly indicate that lens cells which are the target of diphtheria toxin mediated cell ablation techniques persist for a significant time during development and thus place limitations on the interpretations of results obtained using this technique. PMID- 1426069 TI - Association of calpain with insoluble pellet of rat lens. AB - Calpains are calcium-activated neutral proteases found in many tissues including the lens. The purpose of this research was to localize calpain in various biochemical fractions of the rat lens. Lenses were homogenized (with and without added calcium) and separated into water-soluble and -insoluble fractions, which were further extracted with urea, NaOH, and SDS. Of the total calpain 10% was insoluble. In the lens calpain was found to be both insoluble and associated with the membrane. Extraction of calpain from the insoluble fraction suggested calpain was loosely and tightly associated with the membrane. Calpain associated with membrane-rich fractions was obtained from discontinuous sucrose gradients, confirming the above. Calcium increased the amount of calpain associated with the insoluble fraction up to 30% of the total calpain. When the calcium was chelated, this calpain once again became soluble, and its specific activity was higher than water-soluble calpain. The translocation of calpain from the water-soluble fraction to insoluble fractions by calcium may be important because: (1) it may bring calpain into proximity with its substrates; and (2) it may activate calpain, since membrane phospholipids lower the protease's calcium requirement. PMID- 1426070 TI - Cytochrome P450-mediated prostaglandin omega/omega-1 hydroxylase activities in porcine ciliary body epithelial cells. AB - The ocular hypotensive effect of topically applied prostaglandins (PGs) is well documented. Although PGs introduced in the posterior chamber accumulate in the anterior tissues (e.g. iris/ciliary complex), little is known about the metabolism of PGs by these tissues. We have recently found that non-pigmented epithelial (NPE) cells and pigmented epithelial (PE) cells are readily separated from porcine ciliary body and cytochrome P450-dependent xenobiotic metabolism is considerably higher in NPE cells than in PE cells. We have therefore investigated in this study the cytochrome P450-mediated PG omega/omega-1 hydroxylase activities of porcine ciliary epithelial cells. The NPE cells show about three times higher activities than do PE cells; the NPE cells, in fact, demonstrate the highest PG omega/omega-1 hydroxylase activities among different ocular tissues. Both omega and omega-1 hydroxylases show broad substrate specificities and hydroxylate PGA1, A2, E1, E2, and lauric acid. The omega/omega-1 hydroxylase activities of NPE and PE, as determined with PGA2 and lauric acid as substrates, are enhanced or induced by treatment of primary cultures of the individual epithelial cells with clofibrate, both activities reaching maximum levels within 48 hr of induction. The induced activities are inhibited almost completely by cycloheximide and actinomycin D. The omega/omega-1 hydroxylase activities of both NPE and PE cells require NADPH and molecular oxygen, are associated with the microsomal fraction, respond to inducers such as clofibrate, and are inhibited by metyrapone and SKF525 A (inhibitors of P450 enzymes). These results support the suggestion that PG omega/omega-1 hydroxylations by NPE and PE are cytochrome P450 mediated reactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426071 TI - 1992 recipient of the Paul Kayser International Award of Merit in Retina Research. PMID- 1426072 TI - Water binding capacity of mixtures of lens crystallins. AB - The water binding capacity of mixtures of bovine lens crystallins were investigated by combined differential scanning calorimetry and thermogravimetric analysis techniques. Binary, ternary and quaternary mixtures of alpha, beta H, beta L, and lower molecular weight (LMW) crystallins were prepared in proportion of their natural abundance. The percentage of non-freezable water of the total water content was used as an index of the bound water in all these mixtures and it was obtained as a function of crystallin concentration. These experimental values were compared to theoretical values that were calculated from the water binding capacity of individual crystallins obtained previously [Bettelheim and Popdimitrova (1990) Exp. Eye Res. 50, 715-8]. The calculations were based on the assumption that the mixtures of crystallins have the same intermolecular interactions that exist in the individual crystallins. Thus, the difference between the experimental and theoretical curves is an indicator of the type of interactions that may exist among the different crystallins. In all mixtures the experimental bound water was higher than the theoretical, predicted value at physiological concentrations. The water binding capacity of the lyophilized thin lens sections, on the other hand, was lower than the theoretical, predicted value. PMID- 1426073 TI - Photoreceptor plasticity in the albino rat retina following unilateral optic nerve section. AB - Rhodopsin content of the retina increased when an albino rat was moved to a lower intensity cyclic light, and decreased when moved to a higher intensity. Unilateral optic nerve section was employed to test if intact optic nerves are necessary to maintain regulation of rhodopsin when albino rats are switched between two intensities, 3 lx and 600 lx (12 hr/12 hr, cyclic light). The ability to regulate rhodopsin content was altered but not lost in the eye which had the optic nerve transected. This alteration was in the direction of incomplete up regulation when the intensity change was from high to low, and was in the direction of excessive down-regulation when the intensity change was from low to high. This indicates that efferent fibers from the brain to the retina may be involved in the regulation of rhodopsin content. Using histological techniques, cell number and rod outer segment (ROS) length were measured: surgery alone had no effect on ROS length or outer nuclear layer thickness and in all cases ROS lengths were inversely related to habitat illuminance. PMID- 1426075 TI - Electrophysiological properties of neurones following mild and acute retinal ischaemia. AB - Early electrophysiological changes following acute retinal ischaemia were studied by recording single or multiunit retinal ganglion cells and the electroretinogram (ERG) in barbiturate anaesthetized cats. Retinal ischaemia was initiated photochemically by platelet aggregation in retinal vessels which had been irradiated with monochromatic green light following an intravenous injection of Rose Bengal dye. No physiologically active ganglion cells were found within, or close to, the irradiated sites with chorioretinal oedema. On the other hand, in the areas 5-20 degrees away from the irradiation sites, ganglion cells had abnormally raised spontaneous (background) firing which obscured visually driven firing. The retinal areas where no physiologically active ganglion cells were found showed histopathological changes which are similar to those described for glutamate-induced retinal damage. Retinal areas where depolarized retinal ganglion cells were located, however, showed only minor vacuolation of the ganglion cell fibre layer. Early global electrophysiological changes following photochemically induced retinal vascular lesion were consistent with those predicted from the findings in the single cell study. Vascular lesions produced with high irradiation energy (10-30 J), which promote extensive chorioretinal oedema, resulted in gradual loss of visually responsive ganglion cells. Lesions produced by low-energy irradiation (2 J), causing slight narrowing of the blood columns in the vessels, on the other hand, resulted in significant increases in the amplitude and the implicit time of the ERG b-wave and the background firing of multiunit retinal ganglion cells. Electrophysiological changes associated with mild retinal ischaemia are analogous to physiological effects associated with exogenous glutamate or blockade of glutamate uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426074 TI - Extracellular glucose dependence of rhodopsin regeneration in the excised mouse eye. AB - To study the process of rhodopsin regeneration a superfused excised whole eye preparation of the albino mouse was developed. With this preparation, complete regeneration could be observed after each of the first two illuminations (bleaching 15-20%), and incomplete regeneration after a third illumination. Regeneration was minimal at extracellular glucose concentrations of 0 or 1 mM with improved regenerations at higher concentrations. Maximum regenerations were observed at glucose concentrations of 4-10 mM. First-bleach regenerations were as follows: 0 mM glucose, 20%; 1 mM, 8%; 2 mM, 45%; 3 mM, 82%; 4 mM, 115%; 5.1 mM, 121%; 7 mM, 120%; and 10 mM, 126%. The effects of reduced glucose were reversible. After an initial bleach with 0 or 1 mM extracellular glucose that exhibited minimal regeneration, the re-addition of glucose (5.1 mM) restored the ability of the eye to regenerate rhodopsin following a second bleach, but only to the level prior to that bleach. Mitochondrial substrates fumarate (10 mM) or pyruvate (10 mM) partly substituted for glucose, exhibiting first-bleach regenerations of 56 and 85%, respectively. PMID- 1426076 TI - The glycation and cross-linking of isolated lens crystallins by ascorbic acid. AB - Individual lens crystallins were isolated from calf lens extracts and incubated in the presence of ascorbic acid for 3 weeks under aerobic conditions. Both alpha crystallin and beta H-crystallin rapidly cross-linked to form high molecular weight proteins, which did not enter the resolving gel on SDS-PAGE. Beta L crystallin was somewhat less reactive, but gamma-crystallin showed little or no crosslinking. Gamma-crystallin, however, was almost equivalent to the other crystallins as a substrate for glycation. This was measured by: (a) the binding of protein to a boronate affinity column; (b) the incorporation of 3H from NaB3H4 into protein; (c) amino acid analysis of the modified proteins to estimate the extent of lysine modification; and (d) the incorporation of [1-14C]ASA into individual crystallins. When the separated crystallins were combined with [125I]gamma-crystallin and incubated with ascorbic acid, radioactivity was readily incorporated into the cross-linked products with other crystallins, but again not with gamma-crystallin itself. Gel filtration chromatography of a mixture of [125I]gamma-crystallin and alpha-crystallin showed the formation of a complex between gamma- and alpha-crystallins. These data suggest that all crystallins are glycated, but that cross-linking occurs preferentially between proteins, which are already bound together non-covalently. PMID- 1426077 TI - A specific, sensitive, and rapid method for the determination of glutathione and its application in ocular tissues. AB - A method for specific determination of glutathione (GSH) is described. This method utilizes the enzymatic conjugation of GSH to 1-chloro-2,4-dinitrobenzene through reaction catalyzed by glutathione S-transferase. The recovery of GSH as determined by this method is comparable to that in currently used methods. The method is specific for GSH determination. Other sulfhydryl (-SH) compounds including the protein -SH or beta-mercaptoethanol, which are often included in tissue homogenates, do not interfere with GSH determination. Acid extraction of the tissue is not required in this method and comparatively smaller amounts of tissue samples (as little as 20 microliters of a 10% w/v tissue homogenate) are needed for the analyses. The method when applied for GSH determination in ocular tissues yielded results in agreement with the reported values in literature. Evidence for the sensitivity, accuracy, and convenience of the method is provided by analysing the sample containing GSH in the range of 1-200 nmol by this method. PMID- 1426078 TI - Aspects of the development of Schlemm's canal. AB - We have tried to answer the question of whether the endothelium of Schlemm's canal is derived from and retains properties of blood vessels by studying: (1) the development of Schlemm's canal in human fetal eyes; (2) the existence of Weibel-Palade bodies in human neonatal, adult human and adult monkey eyes; and (3) the presence of blood coagulation Factor VIII-related antigen in adult human and monkey eyes. (1) We observed that the intrascleral plexus of the limbal region extended deep into the sclera forming a deep scleral plexus by the 17th week of gestation. After 17 weeks gestation, extensions from the deep scleral plexus had reached the region of the future corneoscleral meshwork where the trabecular cells appeared oriented circumferentially. The blind endings of these extensions appeared to grow circumferentially in the supposed region of Schlemm's canal and at 27 weeks gestation they formed an incomplete Schlemm's canal. A complete Schlemm's canal was observed in some sections of the limbal region at 28 weeks gestation and at approximately 40 weeks gestation the canal was complete in most sections. (2) Weibel-Palade bodies were found in the endothelium of aqueous veins and in the inner and outer wall endothelium of Schlemm's canal. (3) Blood coagulation Factor VIII-related antigen was detected in the endothelium of the collector channels and Schlemm's canal, as well as in the blood vessels of the other parts of the eye. Our results indicate that the endothelium of Schlemm's canal is derived from a vascular origin and that even in the adult eye it retains some of the properties of a blood vessel. PMID- 1426079 TI - Laser Doppler flowmetry in the optic nerve. AB - Laser Doppler flowmetry (LDF) is a technique that measures relative average velocity, number and flux (number times velocity) of red blood cells in a tissue. In this paper, we demonstrate its application in the optic nerve head tissue, describe the laser delivery and light scattering detection schemes and investigate the effect of the distance between the sites of illumination and detection. We also provide evidence that the flow measured by LDF varies linearly with actual blood flow in the optic nerve and examine the question of the depth of the sampled volume. Experiments in anesthetized cats illustrate potential applications which make use of the high temporal resolution of LDF. These include the response of blood flow to changes in the composition of the breathing gases and changes induced by neuronal stimulation with multiple and single flashes. PMID- 1426080 TI - The Oqual: a new device for measuring the optical quality of the anterior segment of the human eye. AB - An attachment to (Haag-Streit and Topcon) slit-lamps is described. This permits projection of a patterned target into the eye and the visual or photographic analysis of the details of the image reflected from the posterior surface of the crystalline lens. A numerical assessment can then be made of the optical quality of the crystalline lens as a whole, although scanning it is also possible. The attachment has also been used successfully for the objective assessment of the patient's post-operative visual acuity following kerato-refractive procedures. PMID- 1426081 TI - A role for endogenous dopamine in circadian regulation of retinal cone movement. AB - Cone movements in the retina of the Midas cichlid (Cichlasoma citrinellum) take place in response both to light and endogenous circadian signals. In the normal light/dark cycle (LD) cone myoids are long at night (50-55 microns), begin to contract before expected dawn, and with light onset contract to their fully contracted positions (5 microns) which are retained throughout the day. In continuous darkness (DD) cone myoids are fully elongate at night, but undergo pre dawn contractions to partially contracted positions which they retain throughout expected day (20-25 microns). To investigate the mechanisms by which circadian signals modulate cone myoid movements in teleost retinas, we have tested the effects on circadian cone movements of optic nerve section, intraocular injection of dopamine agonists or antagonists, and intraocular injection of melatonin. We report here that both light-induced and circadian-driven cone myoid movements can occur in the absence of efferent input from higher centres: both are retained with full amplitude after optic nerve section in vivo. Intraocular injection studies suggest that circadian regulation of cone myoid movement is mediated locally within the eye by dopamine acting via a dopaminergic D2-receptor. Cone myoid contraction can be induced at midnight in LD or DD animals by intraocular injection of dopamine or the D2-receptor agonist LY171555. The partially contracted cones of DD animals at expected mid-day can be induced to fully contract by intraocular injection of dopamine or the D2-receptor agonist, or to elongate by intraocular injection of the dopamine D2-antagonist sulpiride. Furthermore, the pre-dawn cone myoid contraction observed in both LD and DD animals in response to circadian signals can be completely blocked in DD animals by intraocular injection of the D2-antagonist sulpiride shortly before the time of expected light onset. In contrast, circadian cone myoid movements were unaffected by intraocular injection of the D1-receptor agonist SCH23390, or the D1-receptor antagonist SKF38393. In addition, we report that intraocularly injected melatonin had no effect on cone position when injected in the light at mid-day, in darkness at midnight or in darkness just before expected light onset at dawn. However, both melatonin and iodomelatonin induced cone myoid contraction (the light-adaptive movement) when injected in darkness at expected mid-day in DD animals. This paradoxical result is not consistent with observations from other species in which melatonin induces dark-adaptive photoreceptor responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1426082 TI - The potential relationships between aging and cancer. AB - The potential relationships between aging and cancer have received considerable attention in the scientific literature in recent years. While it is clear that the rates of most types of cancer increase with advancing age and that both the processes of aging and those of cancer are time dependent, an unequivocal relationship between the etiology of cancers and the mechanistic processes of aging has yet to be established. This article discusses the potential causal relationships between the processes of aging and the etiologies of most cancers. PMID- 1426083 TI - A murine model for evaluating metastatic potential: characterization of a 90-110 kDa metastasis-binding protein. AB - Reliable discriminatory tests to predict metastatic disease would clearly facilitate the management of cancer in the elderly. We have recently identified a 90-110-kilodalton (kDa) cell surface glycoprotein that is differentially expressed in benign and malignant murine adrenal carcinoma cells. In view of the proteins highly glycosylated nature, we have tested its ability to bind to a panel of agarose-bound lectins. Wheat germ agglutinin (WGA), a lectin specific for terminal sialic acid and N-acetylglucosamine (G1cNAc), had a strong affinity for the metastasis-related protein but failed to detect such a glycoprotein in nonmetastatic cells. Treatment of cells with sialidase to remove terminal sialic acids did not affect the affinity of the protein for the lectin, indicating the presence of terminal G1cNAc. We show by in situ that this metastatic binding protein (MBP) is regionally concentrated on the surface of invasive cells but absent in cells unable to invade. We postulate that MBP plays an active role in cell migration through interactions with beta-1,4 galactosytransferase and basement membrane glycoproteines. PMID- 1426084 TI - Characterization of the absence of an unique DNA-binding protein in senescent but not in their young growing and nongrowing counterparts provides the means to mark the final stage of the cellular aging process. AB - In senescent fibroblasts, the incapability of cell replication is permanent, and may involve the irreversible loss of gene expressions potentiating the engagement in DNA replication. The initial attempt is to identify gene products that are permanently lost in irreversibly growth-arrested cells. In this article, we report the success in identifying a DNA-associated S6 antigen found in the nuclei of growing and growth-arrested young cells, but not in the nuclei of their senescent counterparts. The presence of the S6 antigen is uniform throughout the nucleoplasm, except in the regions of the nucleoli, and found to be associated with condensed chromosomes in mitotic cells. Treatment with RNase does not abolish the antibody staining activity in the nuclei, while treatment with DNase does remove the activity. Equal intensity of S6 antibody staining is observed in transformed, growing, and contact-inhibited young fibroblasts. Significant reduced level of S6 antibody staining activity is found in the nuclei of senescent fibroblasts, indicating the loss of the expression of this protein during cellular aging process. Immunoblotting assay shows that the S6 antigen is of 50 kDa and with a possibility of a 100 kDa as a dimeric precursor. Our results suggests that a permanent turning off of unique gene expression is associated with the onset of senescence or terminal differentiation, and this hypothesis is supported by the characterization of S6 antigen's absence in in vitro-aged fibroblasts. PMID- 1426085 TI - Molecular genetic studies of cellular senescence. AB - The limited doubling potential of normal cells in culture was first proposed as a model for cellular aging by Hayflick in 1961. This phenomenon of in vitro cellular senescence is now well documented for a number of different normal human cell types. In an attempt to determine whether random events or programmed genetic processes were responsible for cellular aging, we performed a series of cell fusion studies. We determined that hybrids from fusion of normal with immortal human cells had limited proliferative potential, indicating that senescence is a dominant phenotype. We exploited the fact that immortality was recessive to assign a large number of different immortal human cell lines to four complementation groups for indefinite division. More recently, we have determined that the introduction of a single normal human chromosome 4 into HeLa (cervical carcinoma) cells by microcell fusion induced senescence in this immortal line. The results of these whole cell and microcell fusion studies support the hypotheses that propose senescence results from active, genetic mechanisms. PMID- 1426086 TI - Exogenous and endogenous DNA modifications as monitored by 32P-postlabeling: relationships to cancer and aging. AB - 32P-postlabeling analysis, a highly sensitive method for the detection and measurement of covalent carcinogen-DNA adducts and other DNA modifications, does not require radioactive test substances and, therefore, can be applied to DNA of mammals, including humans exposed to low doses of environmental or occupational genotoxicants. The basic procedure entails the enzymatic incorporation of 32P label into hydrolysis products of DNA, followed by chromatographic mapping and autoradiography of the 32P-labeled digestion products and quantitative scintillation spectrometry. Microgram amounts of DNA are analyzed: Thus the assay is suited for limited amounts of cells or tissues. Various versions of the assay afford different sensitivities of adduct detection. A single aromatic or bulky/hydrophobic adduct in 10(8)-10(10) nucleotides can be detected and measured (corresponding to 0.3-30 amol adduct/micrograms DNA or 0.1-10 nmol adduct/mol DNA P). In animal models, the assay has been successfully applied to a variety of mutagenic (genotoxic) as well as nonmutagenic carcinogens. In humans, DNA specimens from cigarette smokers, iron foundry workers, and coke oven workers whose total aromatic adduct levels ranged from 1 adduct in 10(6)-10(8) DNA nucleotides have been examined by 32P-postlabeling. The assay also detects DNA modifications--Indigenous (I)-compounds--that increase with age in untreated animals. I-compound profiles and levels are highly species-, strain-, sex-, and tissue-specific, and also depend on diet composition. Caloric restriction, a highly efficient method for improving resistance to carcinogenesis and extending life span, increased rather than decreased I-compound levels in various tissues of male rats. Nonmutagenic hepatocarcinogens reduced levels of I-compounds in the target organ. Because of the specificity of this effect, reduction of I-compound levels appears to represent a novel biomarker for the action of nonmutagenic carcinogens. DNA from various hepatomas was found largely devoid of I-compounds. The results support a possible antineoplastic and antiaging role of these DNA modifications. PMID- 1426087 TI - Explanations for reduced tumor proliferative capacity with age. AB - Tumors in general occur more frequently in older people, but many of the common tumors appear to be less malignant in older hosts. In this article mechanisms of tumor enhancement are reviewed, and those that are age-sensitive are emphasized. In this regard, our earlier experimental work suggested that age-associated immune change (immune senescence) is most important in explaining reduced tumor growth. We have found that unstimulated spleen cells in culture produce a tumor enhancing factor (TEF) that enhances B16 murine melanoma cell proliferation. TEF, and others, such as lymphocyte-induced angiogenesis factor (LIA) and various other autocrine growth factors, may stimulate malignant cells in cancer-bearing hosts. An age-associated reduction in those factors could account for the observed reduced tumor growth and spread in hosts of advanced age. PMID- 1426088 TI - New models to define factors determining the growth and spread of human prostate cancer. AB - The incidence of many cancers shows a sharp increase with age. This is particularly true of prostate cancer, which arises in many older males. Little or no morbidity is observed as the tumor develops in situ in the prostate. However, once malignant cells escape from the primary lesion and metastasize, the disease assumes a much more serious course. Here we report on the activity of human prostate cancer cells in culture as well as their behavior when transplanted into nude mice. In vitro, several lines of prostate carcinoma cells obtained from metastatic lesions were embedded in reconstituted basement membrane proteins (Matrigel) and found to exhibit highly invasive activity as observed with malignant cells from other types of tumors. Also, we report an improved method for obtaining an increased growth of human prostate cancer cells in nude mice by injecting these cells in Matrigel. Since there are no adequate animal models of prostate cancer, the systems described here may prove useful in defining events underlying the development and progression of the tumor cells to malignant status, as well as facilitate the analyses of novel therapeutic agents to prevent the growth and the spread of this cancer. PMID- 1426089 TI - Overview of cancer and aging: a mechanistic perspective. AB - Cancer and aging are approached from the standpoint of damaging agents affecting target cell, local cellular environment, and the organism as a whole. The effects of exogenous agents are represented in a model emphasizing absorption, organismic disposition, and cellular disposition. Endogenous agents are represented similarly. The extent of endogenous damage is illustrated. Factors in the expression of damage as a toxic endpoint are emphasized, with the example of caloric restriction used as an example of environmental modulation of response. PMID- 1426090 TI - Effect of caloric restriction on age-associated cancers. AB - Caloric restriction (CR) without malnutrition in mice and rats reduces the incidence of spontaneous tumors and delays their appearance while increasing maximum life span. These results depend largely on CR per se, and not on low intakes of fat or other nutrients. Although most studies have tested CR imposed early in life, CR started in midadulthood also retards cancer and aging. The way(s) by which CR impedes cancers remain unclear, but possibilities include less cellular oxidative damage, retarded immunologic aging, hormonal changes, less energy available for cell proliferation, reduced exposure to dietary carcinogens and promoters, enhanced DNA repair, and less carcinogen activation. Far less is known about the relationship between caloric intake and cancer incidence in humans; however, recent findings suggest a positive association for certain cancers. PMID- 1426091 TI - Dietary alteration in the rates of cancer and aging. AB - Both variation of diet and comparative analysis are used to evaluate the effects of nutrition on mortality and cancer. The effects of caloric restriction (CR) are compared in multiple strains raised under similar conditions for a diet developed to assist breeding, and for a standard diet. A standard analysis, using "aging rates," is of limited use for understanding the effects of CR in delaying mortality in certain strains. However, when the effect of the diets on body weight and the known effects on sex-specific P-450 isoenzyme expression are compared, these effects suggest a mechanism for the action of CR. By comparative analysis, the effect of CR on tumor pathology suggests that the same mechanisms responsible for inhibiting reproduction may be responsible for delaying the aging related increase in incidence of diseases. Based on these data, the adaptive/longevity-related process theory of CR is modified to incorporate aspects of the disposable soma theory of aging, as well as pleiotropism. PMID- 1426093 TI - The role of glutathione in aging and cancer. AB - The incidence and mortality rates from most cancers increase exponentially with age. It is likely that this aging phenomenon is partially due to specific changes that occur in the host resulting in an increased susceptibility to neoplasia. Our hypothesis is that one such host factor is a deficiency in GSH, based on the importance of this compound in the detoxification of a wide variety of exogenous and endogenous carcinogens and free radicals, as well as in the maintenance of immune function. PMID- 1426092 TI - Effects of aging and dietary restriction on DNA polymerases: gene expression, enzyme fidelity, and DNA excision repair. AB - Hepatic DNA polymerases isolated from young and old C57BL/6N mice fed ad libitum or calorically restricted differed in chromatographic characteristics, binding affinity for DNA template-primer, specific activity, and fidelity of synthesis. DNA polymerase alpha total and specific activity declined slightly, while the nucleotide misincorporation frequency increased dramatically, with increased age of the donor animals. A positive correlation was observed between polymerase alpha specific activity and the affinity of enzyme binding to activated DNA template-primer. Both the age-associated decline in enzyme activity and the decrease in fidelity of synthesis were modified by dietary restriction, with higher specific activity levels and lower misincorporation frequencies for DNA polymerases from dietarily restricted animals compared with ad libitum animals of all ages. Fidelity of both DNA polymerase alpha and beta increased following treatment with the phosphoinositide hydrolysis product inositol-1,4-bisphosphate. The data suggest that dietary restriction could play an important role in decreasing the age-associated decline in function of physiological systems sensitive to decreased or defective DNA synthesis. PMID- 1426094 TI - Food industry perspectives on the mature market. PMID- 1426095 TI - Negative regulators of hematopoietic stem cells and progenitors. PMID- 1426096 TI - Characteristics of a novel rat anti-mouse platelet monoclonal antibody: application to studies of megakaryocytes. AB - Using murine platelets as an immunogen, a rat monoclonal antibody (designated 4A5) that recognizes only murine blood platelets and marrow megakaryocytes was developed. The extent of binding of 4A5 to platelets was dependent upon their state of activation. Following phorbol ester, ionophore, or thrombin stimulation of resting platelets, a decrease of > 50% in the binding of 4A5 was observed by flow cytometry. This decrease in antibody binding to the platelets was accompanied by an increase in antibody released into the platelet-free supernatant following platelet activation. When platelets were first radioiodinated, followed by activation and incubation of the platelet-free supernatant with 4A5-derivatized beads, no precipitable counts were observed compared with control resting platelets. This suggests that antibody release was related to an activation-dependent conformational change in the 4A5 epitope. Following solubilization of biotinylated platelets, 4A5 bound to an 80-kd membrane protein. Immunohistochemical studies with 4A5 showed that megakaryocytes could be identified both in vitro and ex vivo. When marrow was first stained histochemically with 4A5 followed by staining for acetylcholinesterase, the distribution of stained cells was similar. Flow cytometric analysis using 4A5 and propidium iodide showed that the antibody could be used to identify megakaryocytes for ploidy analysis in vivo or in vitro. 4A5 was capable of inducing a moderate thrombocytopenia in mice compared with polyclonal anti platelet serum. When bound to plastic or to magnetic beads, 4A5 could be used to purify murine megakaryocytes to homogeneity. The data suggest that monoclonal antibody 4A5 will be useful in quantitative studies of murine platelets and megakaryocytes. PMID- 1426097 TI - Bone marrow natural suppressor cells inhibit the growth of myeloid progenitor cells and the synthesis of colony-stimulating factors. AB - Natural suppressor (NS) cells, which nonspecifically suppress immune responses, are generally found at sites of hemopoietic generation or regeneration. Murine bone marrow NS cells were activated by recombinant interleukin 3 (rIL-3) or recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and produced a soluble suppressor factor. In the present study, the soluble suppressor factor from bone marrow NS cells was found to be a potent inhibitor of myeloid colony formation at concentrations below those required for immunosuppression. NS cell supernatants inhibited the growth of granulocyte macrophage colony-forming units (CFU-GM), granulocyte erythrocyte macrophage megakaryocyte colony-forming units (CFU-GEMM), and erythroid colony-forming units (CFU-E) to a similar extent. Neutralizing anti-transforming growth factor beta (TGF-beta) reversed the suppressive effects of the supernatants, suggesting that TGF-beta was involved in the suppression. The NS cell supernatants also inhibited the production of colony-stimulating activity by bone marrow stromal cells and the transcription of GM-CSF mRNA by activated T cells. These data suggest that NS cells are important regulators of hemopoiesis. NS cells, which are non-adherent, radioresistant non-T cells resident in the bone marrow, were shown to be sensitive to treatment with the lysosomotropic agent, L-leucine methyl ester, suggesting that the NS cells may be of large granular lymphocytic or monocytic lineage. Cytotoxicity studies revealed that cells in the NS population had natural cytotoxic (NC), but not natural killer (NK) activity. PMID- 1426099 TI - Relationship of [3H]Ara-C incorporation and response to therapy with high-dose Ara-C in AML patients: a Leukemia Intergroup study. AB - Pretherapy bone marrow (BM) aspirates of 143 patients with acute myeloid leukemia (AML) were incubated simultaneously with bromodeoxyuridine (BrdU) and tritiated cytosine arabinoside ([3H]Ara-C) to determine the labeling index (LI) and extent of [3H]Ara-C incorporation. Of 143 AML patients, 121 received high-dose Ara-C (HDAra-C) as a single agent for induction therapy (55 newly diagnosed, 66 in first relapse), whereas 22 received HDAra-C plus mAMSA. The data demonstrate that a subset of patients who will fail HDAra-C remission induction therapy because of drug-resistant disease can be prospectively identified on the basis of the low amount of Ara-C incorporated by their leukemia cells. PMID- 1426098 TI - In vivo cell cycle characteristics of pediatric leukemia patients. AB - Following i.v. bromodeoxyuridine infusion, a double-label technique using in vitro tritiated thymidine was used to determine the labeling index (LI), duration of S-phase (Ts), and cell cycle time (Tc) in pediatric leukemia patients. Eleven patients with acute lymphoblastic leukemia (ALL) and six patients with acute nonlymphoblastic leukemia (ANLL) were studied. Results of cell cycle kinetic studies are given for each group. Although median values for AML and ALL patients are similar to values reported in previous studies, there is a wide range of values among individual patients. The variation among the kinetic properties of blast cells in these patients reflects the heterogeneity of the acute leukemias of childhood. Further studies will be done to determine if these parameters correlate with outcome of therapy for pediatric leukemia patients. PMID- 1426100 TI - Interleukin 1 augments the expression of the interleukin 2 receptor alpha-chain in interleukin 6-stimulated myeloid cells by a transcriptional and posttranscriptional mechanism. AB - We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2R alpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2R alpha in T cells. Thus, in the present study, we investigated whether IL-1 affects the kinetics of IL-6 induced IL-2R alpha expression in M1 cells. By cytofluorometry, we find that surface expression of IL-2R alpha at 24 h after induction by IL-6 is strongly enhanced by IL-1. However, IL-1 does not change the transient kinetics of expression of IL-2R alpha. Binding data and Scatchard analysis support these results and show an increase from 3100 to 17,620 low-affinity IL-2 binding sites per cell without any change in affinity after induction of M1 cells by the combination of IL-6 and IL-1. By Northern analysis, we find that the increase in IL-2R alpha surface expression after treatment with IL-6 and IL-1 occurs in parallel with an increase in IL-2R alpha but not IL-2R beta mRNA expression. By nuclear run-on analysis and actinomycin-D chase experiments, we find that the increase in IL-2R alpha mRNA expression is due to both an increase in IL-2R alpha gene transcription and to an increase in IL-2R alpha mRNA stability. These data suggest that the IL-6-induced expression of IL-2R alpha can be specifically up regulated by IL-1, however, without affecting the transient nature in expression of IL-2R alpha. PMID- 1426101 TI - An age-related reduction in the replicative capacity of two murine hematopoietic stroma cell types. AB - Two stromal cell types, myofibroblasts and endothelial-like cells, that were identifiable by structural and antigenic specificities, were obtained from murine bone marrow and spleen of young, middle-aged, and old mice of two strains and sexes and grown in liquid culture for 9 or 10 days. As expected, there were more total nucleated cells per organ in the old mice (with larger organs) than in the young mice. However, the concentration of stromal colony forming cells was greater in the young mice, resulting in the number of colony forming cells per organ not being significantly different in most comparisons. The in vitro replicative capacity of the two stromal cell types from both organs in all age groups was determined by clone size distribution assays. In all instances the number of cell doublings achieved was statistically significantly greater in the stromal cell clones from young mice than those from old mice. The cell doubling capacity of the middle-aged mice fell between that of the young and the old mice and in most instances that difference was also statistically significant. It was concluded that these in vitro findings constituted a biomarker of aging in these tissues and that this was significant in relation to previous in vivo and in vitro work by these authors and by others reporting the inferiority of aged bone marrow and spleen stroma to regenerate and to support hematopoiesis. PMID- 1426102 TI - B-lymphocyte-derived burst-promoting activity is a pleiotropic erythroid colony stimulating factor, E-CSF. AB - Human B-lymphocyte-derived erythroid burst-promoting activity (B-BPA) is a pleiotropic, lineage-specific regulator of erythropoiesis. Our present data indicate that B-BPA plays an important role as an erythroid colony-stimulating factor (E-CSF) in modulating progenitor growth and differentiation throughout erythropoiesis. E-CSF has discrete effects on both early (erythroid burst-forming units, BFU-E) and late (erythroid colony-forming units, CFU-E) progenitors from normal bone marrow. In serum-substituted fibrin clot cultures, E-CSF stimulates the proliferation of BFU-E, resulting in an increase in the number of erythroid bursts over a wide range of erythropoietin (Epo) concentrations. We now have shown that E-CSF also acts on CFU-E by increasing their sensitivity to Epo markedly, resulting in a tenfold left-shift in the Epo dose-response curve. Using purified target-cell populations of human and murine erythroleukemia cells that are Epo-independent for growth, we have found that E-CSF stimulates cell proliferation directly, increasing the plating efficiency of these cells in suspension culture by 50%-165%. B-BPA also increased proliferation of these cells in semi-solid medium. Importantly, the combination of E-CSF and Epo resulted in a profound increase in the growth and maturation of the resultant colonies. Therefore, the data indicate that E-CSF can regulate the growth of cells independently of added Epo and, in addition, can synergize with Epo in regulating the growth and differentiation of erythroid progenitors. PMID- 1426103 TI - Regulation of production of activin A in human marrow stromal cells and monocytes. AB - In studies of the regulation of hematopoiesis, increasing attention has focused on the role of bone marrow stromal cells as rich sources of various cytokines. Present studies indicate that marrow stromal cells and monocytes produce activin A, implicating this new cytokine in the paracrine control of hematopoiesis. Activin A, which was initially recognized as a beta A beta A dimeric gonadal protein, was found to potentiate the proliferation and differentiation of erythroid progenitors; both purified erythroid colony-forming units (CFU-E) and K562 cells possess high affinity receptors specific for activin A. Present studies using Western and Northern blots demonstrate the presence of beta A subunits of activin A in the conditioned medium of monocytes and stromal cells and its RNA transcripts in these cells. The presence of functional and homodimeric beta A beta A activin molecule was confirmed through bioassay with or without a blocking antiserum against activin A or an activin binding protein, follistatin; its presence is further supported by a specific enzyme-linked immunosorbent assay (ELISA) in which a monoclonal antibody reacted only with the beta A beta A dimeric form of this molecule. In other experiments, the production of activin A was found to be regulated by various cytokines and regulators. The production of activin A in monocytes was stimulated more than ninefold by treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF). Activin A expression was also stimulated, albeit less potently, by bacterial lipopolysaccharide (LPS) and gamma-interferon. On the other hand, the expression of activin A in marrow stromal cells was upregulated by incubation with tumor necrosis factor-alpha (TNF-alpha), LPS, and interleukin 1 alpha (IL-1 alpha). Therefore, we propose that the local production of activin A in the microenvironment within bone marrow may fine tune the regulation of steady-state hematopoiesis. In addition, this factor may normally be produced at minimal levels, but under certain situations may be further induced to provide important biological functions. PMID- 1426104 TI - Effects in vivo of recombinant human inhibin on myelopoiesis in mice. AB - Inhibin, a protein dimer, has been implicated in negative regulation of human erythropoiesis in vitro. In this study, purified recombinant human (rhu) inhibin was assessed for its effect in vivo on the proliferation of hematopoietic progenitor cells in C3H/HeJ mice. Administration of single doses of inhibin i.v. to mice resulted 24 hrs later in significant decreases in cell cycling status of marrow and splenic granulocyte-macrophage (CFU-GM), erythroid (BFU-E) and multipotential (CFU-GEMM) progenitors. While no apparent effect was observed on marrow cellularity or on absolute numbers of marrow CFU-GM and BFU-E, inhibin significantly reduced absolute numbers of marrow CFU-GEMM, spleen nucleated cellularity and also absolute numbers of CFU-GM, BFU-E and CFU-GEMM in the spleen. The results demonstrate in vivo myelosuppressive effects for inhibin and demonstrate that effects in vivo are not restricted to erythropoiesis. PMID- 1426105 TI - On the regulation of repetitive firing in lumbar motoneurones during fictive locomotion in the cat. AB - Repetitive firing of motoneurones was examined in decerebrate, unanaesthetised, paralysed cats in which fictive locomotion was induced by stimulation of the mesencephalic locomotor region. Repetitive firing produced by sustained intracellular current injection was compared with repetitive firing observed during fictive locomotion in 17 motoneurones. During similar interspike intervals, the afterhyperpolarisations (AHPs) during fictive locomotion were decreased in amplitude compared to the AHPs following action potentials produced by sustained depolarising current injections. Action potentials were evoked in 10 motoneurones by the injection of short duration pulses of depolarising current throughout the step cycles. When compared to the AHPs evoked at rest, the AHPs during fictive locomotion were reduced in amplitude at similar membrane potentials. The post-spike trajectories were also compared in different phases of the step cycle. The AHPs following these spikes were reduced in amplitude particularly in the depolarised phases of the step cycles. The frequency-current (f-I) relations of 7 motoneurones were examined in the presence and absence of fictive locomotion. Primary ranges of firing were observed in all cells in the absence of fictive locomotion. In most cells (6/7), however, there was no relation between the amount of current injected and the frequency of repetitive firing during fictive locomotion. In one cell, there was a large increase in the slope of the f-I relation. It is suggested that this increase in slope resulted from a reduction in the AHP conductance; furthermore, the usual elimination of the relation is consistent with the suggestions that the repetitive firing in motoneurones during fictive locomotion is not produced by somatic depolarisation alone, and that motoneurones do not behave as simple input-output devices during this behaviour. The correlation of firing level with increasing firing frequency which has previously been demonstrated during repetitive firing produced by afferent stimulation or by somatic current injection is not present during fictive locomotion. This lends further support to the suggestion that motoneurone repetitive firing during fictive locomotion is not produced or regulated by somatic depolarisation. It is suggested that although motoneurones possess the intrinsic ability to fire repetitively in response to somatic depolarisation, the nervous system need not rely on this ability in order to produce repetitive firing during motor acts. This capability to modify or bypass specific motoneuronal properties may lend the nervous system a high degree of control over its motor output. PMID- 1426106 TI - Optokinetic nystagmus in the rabbit and its modulation by bilateral microinjection of carbachol in the cerebellar flocculus. AB - 1. In the alert, pigmented rabbit, eye movements were recorded during optokinetic nystagmus (OKN) and during optokinetic after nystagmus (OKAN). These responses were elicited by steps in surround-velocity ranging from 5-110 degrees/s during binocular as well as monocular viewing. 2. In the baseline condition, OKN showed an approximately linear build-up of eye velocity to a steady-state, followed by a linear decay of eye velocity during OKAN after the lights were turned off. Build up during binocular viewing was characterized by a constant, maximum eye acceleration (about 1 degree/s2) for stimulus velocities up to 60 degrees/s. OKAN, instead, was characterized by a fixed duration (about 10 s) for stimulus velocities up to 20 degrees/s. Steady-state eye velocity saturated at about 50 degrees/s. 3. Monocular stimulation in the preferred (nasal) direction elicited a build-up that was on average twice as slow as during binocular stimulation. Steady-state velocity during monocular stimulation saturated at about 20 degrees/s. OKAN was of equal duration as during binocular stimulation. In the non preferred direction, a very irregular nystagmus was elicited without velocity build-up. The stronger response to binocular stimulation, compared to the responses under monocular viewing condition in either nasal and temporal direction suggests potentiation of the signals of either eye during binocular viewing. 4. OKN and OKAN were re-assessed after intra-floccular micro-injection of the nonselective cholinergic agonist carbachol. In the binocular viewing condition, eye-acceleration during build-up was strongly enhanced from 1 degree/s2 before to 2.5 degrees/s2 after injection. The saturation level of steady-state eye velocity was also increased, from 50 degrees/s before to more than 60 degrees/s after carbachol. The duration of OKAN, however, was shortened from 10 s before to 6 s after injection. The response to monocular stimulation in the preferred direction revealed similar changes. 5. The flocculus appears to be involved in the control of the dynamics of OKN in the rabbit. Cholinergic mechanisms affect the floccular control of the rate at which slow-phase velocity can be built up and the rate of decay of eye velocity during OKAN. Cholinergic stimulation of the flocculus enhances the dynamics of OKN, while velocity storage is shortened. PMID- 1426107 TI - Functional organization of the nociceptive withdrawal reflexes. II. Changes of excitability and receptive fields after spinalization in the rat. AB - The spatial organization of the cutaneous input to hindlimb withdrawal reflexes was studied in spinalized, decerebrated, unanesthetized rats. Reflex activity in plantar flexors of the digits, pronators of the foot, dorsiflexors of the digits, and/or the ankle and flexors of the knee was recorded with electromyographic techniques for up to 12 h after spinalization. Graded mechanical (pinch) and thermal stimulation (CO2 laser) of the skin were used. Reflexes were absent ("spinal shock") during approximately 10-20 min after spinalization. The reflex thresholds for pinch and CO2 laser stimulation then decreased considerably during the following 5-8 h. After this time, even mild pressure (less than 0.1 N/mm2) on the skin was sufficient to evoke a reflex in most muscles. During the period from about 0.5-3 h after spinalization, the nociceptive receptive field of each muscle usually corresponded to the area of the skin withdrawn by the muscle. Maximal responses were evoked from the area of the receptive field maximally withdrawn. During this period, responses to innocuous pinch were evoked mainly from the most sensitive area of the receptive fields. Concomitant with the decrease in reflex thresholds, the nociceptive receptive fields expanded for all muscles, often to include areas of the skin not withdrawn by the muscles. For most muscles, reflexes on tactile stimuli were eventually elicited from the entire receptive fields. The receptive fields for thermonociceptive and mechanonociceptive inputs were similar in most muscles. The interossei muscles were exceptional in that they responded very weakly to thermal stimulation. It is concluded that there are neuronal networks in the spinal cord that translate cutaneous nociceptive and tactile input into a withdrawal. However, the control exerted by descending pathways is necessary to maintain a functionally adequate excitability in these reflex pathways and an appropriate size for their receptive fields. PMID- 1426108 TI - Vestibular control of swimming in lamprey. I. Responses of reticulospinal neurons to roll and pitch. AB - A method has been developed for recording the response of single neurons in the lamprey brainstem in vitro to natural stimulation of vestibular receptors. The brainstem dissected together with the intact vestibular apparatus could be rotated in space, in two perpendicular planes (transverse, the roll tilt, and sagittal, the pitch tilt), in one of them up to 360 degrees, and in the other one up to +/- 30 degrees. The responses of single reticulospinal (RS) neurons, in all four reticular nuclei of the brainstem, to roll and pitch were recorded extracellularly and, with small inclinations (up to +/- 45 degrees) also intracellularly. Two types of preparations were used, with and without the rostral part of the spinal cord. In the brainstem preparations, most RS neurons responded both to a definite brain orientation in space and to a change of the orientation (static and dynamic reactions). Responses to roll tilt were similar in all reticular nuclei: all cells were excited with roll tilt towards the contralateral side, this reaction was qualitatively preserved when the roll was performed in combination with different pitch inclinations. Responses to pitch tilt were less clearcut; some neurons were activated with nose-up deflection while others responded to nose-down tilt. In preparations including the spinal cord, responses of RS neurons to roll and pitch tilt differed from those in the isolated brainstem in that they were much less specific and stable. Roll and pitch tilts could trigger the spinal locomotor CPG, which, by sending "efference copy" signals back to the brainstem, produced modulation of RS neurons in relation to the locomotor rhythm. PMID- 1426110 TI - Vestibular control of swimming in lamprey. III. Activity of vestibular afferents: convergence of vestibular inputs on reticulospinal neurons. AB - Experiments were carried out on the in vitro preparation of the lamprey brainstem isolated together with the labyrinths. The brain orientation in space could be changed in steps of 45 degrees by rotation (360 degrees) around the longitudinal axis (roll) or the transverse axis (pitch). Vestibular afferents in the VIII nerve, or reticulospinal (RS) neurons, were recorded extracellularly during roll and pitch. Two main types of afferents could be distinguished. Presumed otolith afferents responded both to a change of position and to a maintained new position. These afferents were classified in several groups according to the position of their zone of sensitivity. For roll, the largest group had their maximal sensitivity around 90 degrees tilt to the ipsilateral side, the next group in size responded at 180 degrees, and only a few afferents were activated by contralateral roll. For pitch, there are groups responding with maximal sensitivity at 90 degrees nose-up, 90 degrees nose-down and at 180 degrees. A minority of afferents were active when the brainstem was in a normal position, i.e. horizontal, with the dorsal side up. Another type of afferent responded only by a high-frequency burst to a change of brain orientation. They were classified as canal afferents in analogy with other species. All tested canal afferents responded to rotation towards ipsi-side down. Pitch tilt revealed two groups that responded to rotation towards either nose-up or nose-down. RS neurons from the anterior and middle rhombencephalic nuclei (ARRN and MRRN) were recorded before and after unilateral transection of the VIII nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426109 TI - Vestibular control of swimming in lamprey. II. Characteristics of spatial sensitivity of reticulospinal neurons. AB - 1. Experiments were carried out on an in vitro preparation of the lamprey brainstem isolated together with intact labyrinths. Responses of reticulospinal neurons from different brainstem reticular nuclei (mesencephalic, MRN; anterior rhombencephalic, ARRN; middle rhombencephalic, MRRN; and posterior rhombencephalic, PRRN) to rotation of the preparation (0 degrees-360 degrees) either in the sagittal plane (pitch tilt, or nose up-down movement) or in the transverse plane (roll tilt, or left-right inclination) were recorded. 2. Responses to roll tilt were qualitatively similar in all nuclei: contralateral side down tilt (in relation to the location of the neuron in the brain) caused an activation of reticulospinal neurons. The angular thresholds for activation differed, however, between nuclei as well as the angle at which the maximal activity occurred. The maximal response for MRN was at 45 degrees, for MRRN and PRRN at 90 degrees, for ARRN at 180 degrees. Thus, the zones of spatial sensitivity differed in different nuclei, and they covered the whole range of possible inclinations in the transverse plane. 3. Responses to pitch tilt were not uniform in the different nuclei. MRN neurons responded preferentially in the range of 45 degrees-90 degrees nose-up inclinations, but a proportion of the cells responded in the range of 45 degrees-90 degrees nose-down inclinations. The ARRN neurons had their maximal response when the brain was turned to a dorsal side-down position (180 degrees). In the MRRN, three subgroups of neurons could be distinguished, the first responding at around 90 degrees nose-down, the second responding at around 90 degrees nose-up and the third responding in both zones. However, the activation in the nose-up zone was less robust: responses in this zone were present only in approximately one half of the experiments. Finally, the PRRN neurons were found to be very heterogeneous, with their zones of sensitivity being distributed throughout the whole space (0 degrees-360 degrees). Thus, also in the sagittal plane, the zones of spatial sensitivity in the different nuclei covered the whole range of possible inclinations. 4. Long-term recording of MRRN neurons having the zone of sensitivity around 90 degrees nose-up showed that this response was rather unstable. Its amplitude varied considerably and could disappear with time to reappear later. These results, together with the fact that in a part of the experiments the MRRN neurons responded only in the 90 degrees nose-down zone (see above), leads us to suggest that the system of spatial orientation can dynamically re-organize.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1426111 TI - Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum. AB - We habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (approximately 5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore x 2.2 magnifying or x 0.5 reducing lenses. Adaptation occurred rapidly and reached about +/- 30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6-8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h0).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1426112 TI - Entrainment of the locomotor rhythm by group Ib afferents from ankle extensor muscles in spinal cats. AB - 1. Previous studies have concluded that the timing of the locomotor rhythm can be strongly influenced by input from group Ib afferents from leg extensor muscles (Duysens and Pearson 1980; Conway et al. 1987). The main objective of the present study was to obtain additional evidence for this conclusion by examining the characteristics of entrainment of the locomotor rhythm by rhythmic stimulation of group I afferents and by rhythmic force pulses in the ankle extensor muscles. 2. A reduced, non-immobilized preparation was developed in spinal cats that allowed isometric contractions of ankle extensor muscles to be elicited by ventral root stimulation during the expression of locomotor activity. The same preparation was used to examine the influence of electrically stimulating group I afferents from the ankle extensors and the effect of rhythmically stretching these muscles. The locomotor rhythm was initiated by sustained mechanical stimulation of the perineum following the administration of Clonidine and, in some preparations, Naloxone. 3. The timing of the onset of flexor burst activity was examined during entrainment with saw-tooth and ramp-and-hold stretches of the ankle extensor muscles. Flexor bursts were initiated about 200 ms following the release from the stretch, and this latency was independent of the entrainment frequency. 4. The locomotor rhythm was readily entrained by rhythmic contractions of the ankle extensor muscles produced by ventral root stimulation provided the magnitude of the contractions was greater than about 10N. Repetitive stimulation of group I muscle afferents from the ankle extensors also entrained the locomotor rhythm, with the timing of motor activity being similar to that during entrainment with rhythmic muscle contractions. Burst activity in the ipsilateral extensors was coincident with the stimulus trains in both cases. This similarity argues for entrainment being produced mainly by input from group Ib afferents. 5. The functional implication of the results of this and previous studies is that input from group Ib afferents during the stance phase of walking acts to inhibit generation of flexor burst activity and to promote extensor activity. The proposal that a decline in Ib activity near the end of the stance phase is involved in regulating the stance to swing transition is discussed. PMID- 1426113 TI - Mammillary body lesions and restricted subicular output lesions produce long lasting DRL performance impairments in rats. AB - Rats given either electrolytic lesions of the mammillary bodies (MB), transection of the descending columns of the fornix (DCF), transection of fibres projecting from subiculum to ventral striatum (SC) or sham operations (SO) were tested in three DRL experiments. DRL-18 efficiency was impaired significantly in MB rats, and non-significantly in DCF and SC rats. Analysis of timing behaviour revealed modifications in all three lesion groups, with a unique pattern in the SC group. DRL-36 efficiency was significantly impaired in all three lesion groups; the SC group again showed a unique timing pattern. Finally we assessed retention of DRL 36 in SO rats given mammillary body lesions. There was a lesion-induced impairment, smaller than that seen with postoperative training. We propose that the subicular output plays an important part in normal DRL performance; that the subicular outputs to the mammillary bodies and ventral striatum play independent roles in DRL; and that the effects of mammillary body lesions resemble those of hippocampal lesions because of the important functional relationship between subiculum and the mammillary bodies. PMID- 1426114 TI - Activity of lateral vestibular nucleus neurons during locomotion in the decerebrate guinea pig. AB - The influence of locomotor activity upon neurons in the lateral vestibular nucleus was investigated in precollicularly-postmamillary decerebrate guinea pigs. Out of 95 recorded neurons, 24 were identified as vestibulospinal and 71 had no descending projections. Locomotor activity occurred either spontaneously or was prompted by electrical stimulation of the mesencephalic locomotor region. Natural vestibular stimulation was supplied by tilting the animal about its longitudinal axis. Locomotor rhythmic limb muscle activity was accompanied by an increase in the firing frequency in the vast majority of investigated neurons. The increase in frequency was observed at the beginning of ipsilateral forelimb extensor muscle activity. Only in a few non-vestibulospinal neurons was the spontaneous activity depressed during locomotion. An increase in evoked responses was observed in almost all vestibulospinal neurons and in two thirds of the neurons without descending projections. A decrease in evoked responses was observed in one quarter of non-vestibulospinal neurons. During locomotion, the mean and maximal frequencies of evoked neuronal impulse activity changed, but the phase lag of these changes was not altered significantly. The results suggest an enhancement of vestibulospinal influences during locomotion, thus providing a high level of tonus in antigravitational muscles. This is interpreted as a mechanism to ensure that equilibrium is maintained during motion in different gaits and postures. PMID- 1426115 TI - Interaction of active and passive slow eye movement systems. AB - Independent target and background motions have been used to generate conflicting activity within the pursuit and optokinetic systems. Subjects were required to pursue a small target against a structured background which moved independently. Selective enhancement of the response to the target generated high-gain active pursuit which dominated the eye movements. Passive eye movements induced during relative target and background motion are not normally directly quantifiable due to their low gain. By reducing the gain of the active pursuit optokinetically induced eye movements were enhanced and quantified. Three techniques are described for degrading active pursuit: tachistoscopic, eccentric and pseudorandom methods of target presentation. Our results demonstrate the synchronous input of active and passive eye movement drives to the oculomotor system and illustrate their interaction. PMID- 1426116 TI - Oculo-manual coordination control: ocular and manual tracking of visual targets with delayed visual feedback of the hand motion. AB - The aim of this study was to examine coordination control in eye and hand tracking of visual targets. We studied eye tracking of a self-moved target, and simultaneous eye and hand tracking of an external visual target moving horizontally on a screen. Predictive features of eye-hand coordination control were studied by introducing a delay (0 to 450 ms) between the Subject's (S's) hand motion and the motion of the hand-driven target on the screen. In self-moved target tracking with artificial delay, the eyes started to move in response to arm movement while the visual target was still motionless, that is before any retinal slip had been produced. The signal likely to trigger smooth pursuit in that condition must be derived from non-visual information. Candidates are efference copy and afferent signals from arm motion. When tracking an external target with the eyes and the hand, in a condition where a delay was introduced in the visual feedback loop of the hand, the Ss anticipated with the arm the movement of the target in order to compensate the delay. After a short tracking period, Ss were able to track with a low lag, or eventually to create a lead between the hand and the target. This was observed if the delay was less than 250 300 ms. For larger delays, the hand lagged the target by 250-300 ms. Ss did not completely compensate the delay and did not, on the average, correct for sudden changes in movement of the target (at the direction reversal of the trajectory). Conversely, in the whole range of studied delays (0-450 ms), the eyes were always in phase with the visual target (except during the first part of the first cycle of the movement, as seen previously). These findings are discussed in relation to a scheme in which both predictive (dynamic nature of the motion) and coordination (eye and hand movement system interactive signals) controls are included. PMID- 1426117 TI - Developmental aspects of stance regulation, compensation and adaptation. AB - Recordings of electromyographic (EMG) leg muscle activity, head and joint movements and platform torque were taken in healthy subjects within three age groups (approximately 6, 10 and greater than 22 years) standing upright upon a sinusoidally moving treadmill. The sinusoidal frequency was randomly changed between 0.5, 0.33 and 0.25 Hz, while the amplitude of the deflection was constant (+/- 12 cm). During an adapted sinus, forward inclination of the body at the posterior turning point was associated with a slowly increasing tibialis anterior and decreasing gastrocnemius activity, while straightening of the body at the anterior turning point was associated with a sharply increasing gastrocnemius and decreasing tibialis anterior activity. The angle of forward inclination was greatest in the groups of children and was dependent upon both the sinus frequency and the child's height. The presumed programmed adjustment of the body inclination was such that the net effect of both inertial and gravitational forces acting on the body coincided approximately with the axis of the body at the posterior turning point. Changes of sinusoidal frequency were followed by compensatory responses, the amplitude of which depended upon the velocity of the body's displacement and the height of the subjects. In all three subject groups the response latencies were significantly shorter at the posterior turning point for the gastrocnemius response to a change from 0.5 to 0.25 Hz (105 ms for children and 119 ms for adults) than for the tibialis anterior response to a change from 0.25 to 0.5 Hz for which the values were 162 and 169 ms, respectively. This difference could be attributed to the forward inclination of the body at the posterior turning point which requires an earlier onset of compensatory extensor activity in order to maintain equilibrium. Adaptation to a new sinusoidal frequency occurred within 4 cycles following a change in sinus frequency. The phase shifts between treadmill position and the biomechanical and EMG signals that occurred during the adaptational process suggest that the position of the body's centre of gravity is the variable controlled by the programmed leg muscle activation. In young children the phase shifts during adaptation were absent, which may contribute to their greater instability. It is concluded that posture is continually adjusted in such a way that the resulting torque acting on the body during the treadmill movement becomes minimized. For this regulation load receptors in addition to the classical afferent impulses from visual, vestibular and muscle stretch receptors could play a major role. PMID- 1426118 TI - Distribution of heteronymous Ia facilitation and recurrent inhibition in the human deltoid motor nucleus. AB - Distribution of heteronymous Ia facilitation and of heteronymous recurrent inhibition in motoneurones innervating the anterior part of the deltoid muscle were investigated in normal human subjects following electrical stimulation of the nerves innervating the main muscles of the upper limb. Activation of group I afferents originating from deltoid, biceps, triceps and extensor carpi radialis (ECR) muscles resulted in an early increase in firing probability of voluntarily activated motor units belonging to the anterior part of the deltoid muscle whereas activation of motor axons supplying deltoid, triceps, ECR and flexor carpi radialis (FCR) muscles resulted in an early and long-lasting decrease in firing probability. No effect was seen following activation of group I afferents and motor axons contained in the ulnar nerve. The characteristics of the early facilitation suggest that it is at least partly due to heteronymous Ia monosynaptic connections while these of the long-lasting inhibition suggest that it is at least partly due to heteronymous recurrent inhibition. Their patterns of distribution are discussed with regards to the functional role of the human deltoid. PMID- 1426119 TI - Visual pursuit over textured backgrounds in different depth planes. AB - Several investigators have reported that voluntary pursuit of a moving object is less smooth when it moves over a textured background compared with when it moves over a dark background. Furthermore, when a person fixates a stationary target on a moving background, microdrifts of the eyes occur in the direction of motion of the background. These two facts suggest that OKN is not completely switched off during voluntary pursuit or fixation. Howard and Simpson (1989) found that optokinetic nystagmus (OKN) is only weakly evoked by moving stimuli which are out of the plane of convergence. This led to the prediction that voluntary pursuit of a visual target should be disrupted more by a stationary background in the same depth plane than by a background which is nearer or further away than the pursuit target. Pursuit disruption was measured by the frequency and total amplitude of saccadic intrusions. For horizontal pursuit, disruption was reduced, compared with the coplanar condition, when the textured background was further away than the target but not when it was nearer. For vertical pursuit, disruption was reduced in both the far and near conditions compared with the coplanar condition. In both cases disruption was least when the background was dark. PMID- 1426120 TI - Effects of sensory deprivation upon a single cortical vibrissal column: a 2DG study. AB - Effects of sensory deprivation upon ability of a vibrissa to activate a functional column in the barrel field of somatosensory cortex were examined with 2 deoxyglucose (2DG) autoradiography in the rat. After six weeks of whisker plucking started at birth, and one week of recovery, the cortical column activated by the deprived whisker and labeled with 2DG had a reduced diameter but higher labeling density than the normal vibrissal column. Loss of a peri-barrel labeling zone, possibly due to loss of intracortical activation, is suggested. PMID- 1426121 TI - Complement C1qB and C4 mRNAs responses to lesioning in rat brain. AB - These data show the presence of mRNAs for two complement components (C) in the adult rat brain and describe their responses to experimental lesions. Cortical deafferentation caused elevations in striatal C1qB and C4 mRNAs that coincided temporally and overlapped anatomically with the course of degeneration of corticostriatal afferent fibers. By in situ hybridization, C1qB mRNA in the lesioned striatum was colocalized to cells immunoreactive for CR3, a complement receptor found on microglia-macrophages. The mRNA for SGP-2, a putative C inhibitor in rat, showed parallel changes. Similarly, in hippocampus and other brain regions, kainic acid lesions increased C1qB mRNA. The data suggest that microglia-macrophages and possibly other cells in rat brain rapidly up-regulate C mRNAs in response to deafferentation and local neuron injury. These experimental responses provide models to analyze changes in C components during Alzheimer's disease and other chronic neurodegenerative conditions. PMID- 1426122 TI - Radial glial interaction with cerebral germinal matrix capillaries in the fetal baboon. AB - The occurrence of intraventricular hemorrhage (IVH) is a frequent problem in premature infants delivered between 24 (60%) and 32 weeks (80%) of gestation, a time during which the germinal matrix (GM) is prominent over the head of the caudate nucleus. Most IVH arises from the GM and it has been proposed that an important factor in the pathogenesis of IVH is a weakness of GM capillary walls due to deficient support by surrounding immature glial cells. The purpose of this study was to examine the glial-capillary interaction in the GM of fetal baboons sacrificed at 100 days (54%) gestation, a stage of GM development comparable to that during which human neonatal IVH occurs. Brains from a later gestational stage (162 days, 88%), after GM involution, were also examined. At 100 days of gestational age, the GM was prominent over the head of the caudate and contained vimentin positive, but not glial fibrillary acidic protein positive, radial glial cells which formed endfeet on capillaries in the region. Ultrastructurally, all the GM capillaries examined from this gestational time had complete, continuous endothelia marked by few pinocytotic vesicles and prominent tight junctions. The endothelial cells rested upon uninterrupted basement membranes which were contacted by clearly identifiable glial endfeet. These data show that GM capillaries have morphologies typical of CNS capillaries and suggest that the capillary immaturity within the GM is not a major contributing factor to IVH. PMID- 1426123 TI - Regeneration of dorsal root axons is related to specific non-neuronal cells lining NGF-treated intraspinal nitrocellulose implants. AB - The regeneration of sensory axons from severed dorsal roots can be enhanced by the presence of nerve growth factor (NGF)-treated nitrocellulose strips implanted into an intraspinal lesion cavity. Rather than being directly apposed to the transplant, most regenerating axons are separated from the nitrocellulose by several layers of non-neuronal cells, suggesting that these cells may have a role in the promotion of axonal regrowth. The cellular layers associated with untreated nitrocellulose strips or NGF-treated implants were examined in this study to determine if there were differences in their arrangement or orientation along the implant which might explain some of the possible effects of substrate bound NGF on axonal regrowth. Into a hemisection lesion cavity created in the adult rat lumbar spinal cord NGF-treated or untreated strips of nitrocellulose were placed vertically, with intact pieces of fetal spinal cord (FSC) tissue transplanted along each side. The distal ends of cut dorsal rootlets were apposed to the fetal tissue. Immunocytochemical and electron microscopic examination 30 60 days post-transplantation revealed a distinct layering of cell types along the NGF-treated strips. Closest to the nitrocellulose was a single layer of macrophages, followed by a separate layer of fibroblasts with dense collagen bundles, then a layer of astroglial cells, before reaching the neuropil of the fetal spinal cord tissue. A thickened basal lamina formed between the fibroblast and astrocytic cell layers and bundles of regenerated sensory axons extended along the interface between these two layers. In contrast, non-neuronal cells along untreated nitrocellulose strips were not as well organized, with an intermixing of fibroblasts and astroglial cells and only scattered macrophage like cells. Axons rarely were found in conjunction with this mixed population of cells and, overall, fewer regenerated axons extended into transplants with untreated nitrocellulose. The results demonstrate consistent differences in the composition and organization of non-neuronal cells adjacent to NGF-treated nitrocellulose implants, compared to untreated implants. This suggests that the presence of bound NGF influences the recruitment of various cells from the surrounding transplant tissue as well as from the previously injured dorsal rootlets. The capacity for NGF to promote the regeneration of sensory axons may be an indirect effect that is mediated or potentiated by the non-neuronal cell population that gathers in response to the presence of bound NGF. PMID- 1426124 TI - Protective effect of the NMDA antagonist MK-801 on photochemically induced spinal lesions in the rat. AB - Photochemically induced ischemic lesions in the rat spinal cord were studied using neurological tests and morphological evaluation in order to investigate ischemia-mediated pathophysiological mechanisms in traumatic spinal cord injury. One week after ischemic lesioning, animals were severely impaired with 85% decrease of performance in neurological tests. During the next 2 weeks considerable recovery occurred. Pretreatment with the noncompetitive N-methyl-D aspartate antagonist MK-801 at a dose of 0.5-1.0 mg/kg significantly improved the recovery of function after spinal ischemia while lower doses exerted no protection. Morphologically, no dose-response effect on the extent of tissue necrosis was found, but a significant difference between groups with severe neurological deficit versus mildly affected groups was observed. Immunohistochemical staining for glial fibrillary acidic protein in the area close to the lesion revealed extensive gliosis, while neurofilament immunohistochemistry showed an irregular pattern of fiber loss with large variability between animals. The degree of gliosis or loss of neurofilament immunoreactivity in nonnecrotic tissue was not affected by MK-801. These results suggest that excessive stimulation of N-methyl-D-aspartate receptors participates in the development of spinal cord ischemia and possibly also participates after traumatic spinal cord injury. PMID- 1426125 TI - Brain norepinephrine reductions in soman-intoxicated rats: association with convulsions and AChE inhibition, time course, and relation to other monoamines. AB - The organophosphate chemical nerve agent, soman, causes convulsions, neuropathology, and, ultimately, death. A major problem in treating soman intoxication is that peripherally acting pharmacological agents which prevent death do not prevent seizures. Although a primary cause of these symptoms is the excess of acetylcholine which follows acetylcholinesterase (AChE) inhibition, centrally acting muscarinic blockers, such as atropine, alleviate, but do not block, the convulsive actions of soman. Moreover, there is a relatively weak relationship between CNS reductions of AChE and the incidence of convulsions. There is evidence suggesting that soman intoxication stimulates the release of norepinephrine (NE) in the brain. Recent evidence has implicated NE in the induction and/or maintenance of seizures. Thus, in the present study the relations among soman-induced convulsions, AChE inhibition, and brain NE and other monoamine changes were examined. The time course of brain NE recovery was also determined. Rats were injected (im) with a single dose (78 micrograms/kg) of soman. At this dose 68% of the injected rats developed convulsions. Both convulsive and nonconvulsive rats were sacrificed between 1 and 96 h following soman injection and NE levels in the rostral forebrain and olfactory bulb were determined by HPLC with electrochemical detection. In all convulsive rats NE levels declined substantially. Forebrain NE levels were decreased by 50% at 1 h and 70% at 2 h following soman injection. Recovery of NE began at 8 h and was complete by 96 h following soman administration. Although nonconvulsive rats showed other signs of intoxication, NE levels in these rats were unchanged. Dopamine (DA) and serotonin (5-HT) levels were not significantly affected in either convulsive or nonconvulsive rats. However, 5-hydroxyindoleacetic acid, the major metabolite of 5-HT, and homovanillic acid and 3,4-dihydroxyphenylacetic acid, the two major metabolites of DA, were increased significantly in the forebrain of convulsive, but not nonconvulsive rats, indicating an increase in 5 HT and DA turnover. However, in contrast to the abrupt decline in NE, these increases in DA and 5-HT metabolites were slow and progressive. Taken together, the present results and other recent findings suggest that rapid, sustained NE release could play a role in the induction and/or maintenance of soman-induced convulsions, whereas increased release of 5-HT and DA may be a consequence of seizures. Further investigation of the role of NE in soman-induced convulsions may lead to improved treatment of soman intoxication and a better understanding of the role of NE in other forms of seizures, including human epilepsy. PMID- 1426126 TI - Effects of freezing a segment of peripheral nerve on subsequent protein release and axonal regeneration in the frog. AB - Previous studies in frogs have shown that axons from the proximal stump of a cut nerve will grow toward the distal stump, possibly in response to diffusible trophic factors produced by cells of the nerve sheath. In the present experiments, the synthesis and release of proteins in vitro, from proximal and distal stumps of frog sciatic nerves, were studied 1, 4, and 14 days after nerve section in vivo. Using two-dimensional gel electrophoresis to separate released proteins, a marked increase in the synthesis of two lipoproteins of 37 and 67 kDa was seen, initially in both proximal and distal stumps, but by 14 days these proteins were produced exclusively by the distal stump. To see if the production of these proteins was correlated with subsequent reinnervation of the distal stump, isolated nerve segments were removed from the frogs and either replaced immediately or frozen (to kill sheath cells) and replaced. After 2 weeks, the pattern of newly synthesized proteins released by both the frozen and nonfrozen nerve segments was similar although freezing severely impaired the reinnervation of the nerve segment. These results suggest that although the 37- and 67-kDa lipoproteins may have a role in nerve regeneration, their presence per se is not sufficient to support the reinnervation of a distal stump of a cut peripheral nerve and that additional factors may therefore be required. PMID- 1426127 TI - Photochemically induced transient spinal ischemia induces behavioral hypersensitivity to mechanical and cold stimuli, but not to noxious-heat stimuli, in the rat. AB - Pain-like sensory disorders lasting several days were observed in rats after transient ischemia in the lumbar region of the spinal cord. The ischemia was induced with a recently developed photochemical technique. Rats exhibited strong allodynia, a pain-like reaction to innocuous stimuli, to mechanical stimulation of the caudal trunk, hind limbs, and hind paws, which were areas innervated by the ischemic spinal segments. The rats also expressed hypersensitivity to cold stimuli. However, no changes in sensitivity to noxious heat could be detected with the hot-plate test. Furthermore, no morphological damage could be observed in the spinal cord at the light microscopic level in the majority of rats after transient spinal cord ischemia. The present results indicate that allodynia-like symptoms to mechanical stimuli after spinal ischemia may be mediated by myelinated afferents and could be associated with dysfunction of inhibitory transmission in the spinal cord. We suggest that this pain-related syndrome after spinal ischemia could be considered as an animal model of painful states of spinal origin. PMID- 1426128 TI - Kinematic analysis of upper limb trajectories in Parkinson's disease. AB - The purpose of this study was to analyze the kinematic properties of upper limb trajectories in Parkinson's disease (PD) patients and to investigate the role of visual feedback from the moving limb. Beyond the characteristic bradykinesia, PD patients differed from controls by generating hand trajectories with asymmetrical velocity profiles that lacked smoothness and were composed of a short initial accelerative phase, followed by a prolonged interval composed of alternating decelerative and accelerative phases. In both groups, the reaction times for movements directed away from the body were longer than for movements directed toward the body; this effect was accentuated in PD. In both groups, initial peak accelerations were significantly larger for distally as compared to proximally directed movements. In the absence of visual feedback from the limb a deterioration in the accuracy of reaching the target was observed in both control and PD patients only for distally directed movements. However, this deterioration and the effect of target location on final accuracy was substantially larger in PD. Taken together, our study suggests that in PD visual information is continuously relied upon for ongoing movement correction, therefore accentuating the bradykinesia. The deficit in final accuracy in the absence of visual feedback reflects the important role played by the basal ganglia in sensorimotor integration. PMID- 1426129 TI - Iron accumulation in the rat basal ganglia after excitatory amino acid injections -dissociation from neuronal loss. AB - The current study examines in an animal model the relation of excessive iron accumulation in the basal ganglia to the pathology of Parkinsonism and Hallervoden-Spatz disease. Following a unilateral microinjection of excitatory amino acids, kainate, or quinolinate to the anterior olfactory nucleus/ventral striatal region, an increase in histochemical iron concentration was observed in the ipsilateral ventral pallidum, the islands of calleja, the globus pallidus, the entopeduncular nucleus, the ventral thalamus, and the substantia nigra pars reticulata. The iron was observed both in glia and as intensification of patches in the neuropil. In a second group of rats, after microinjection of ibotenate or quisqualate to the nucleus basalis of Meynert, iron accumulated in the ipsilateral entopeduncular nucleus and pars reticulata of substantia nigra. Increased iron accumulation, compared to that in the contralateral side, was stable for months after a single microinjection. In the basal ganglia distal from the site of EAA injection, no gross morphological changes were associated with the increased iron accumulation. The implications of these findings to the pathology of Parkinson's and Hallervorden-Spatz diseases are discussed. PMID- 1426130 TI - Echinococcus granulosus: study of the in vitro complement activation by protoscoleces by measuring the electric potential difference across the tegumental membrane. AB - Complement activation by protoscoleces of Echinococcus granulosus was studied by analyzing the damage to their tegumental membrane produced by incubation in both normal and hydatid human sera. The state of the apical tegumental membrane was evaluated by measuring the electric potential difference with microelectrodes. Protoscoleces incubated in Ringer-Hepes or in heat-decomplemented normal human serum in the presence or absence of specific antibodies did not show significant variations in the electric potential difference throughout the experiment (P > 0.4 in all cases) and their mean values were -46 +/- 3, -43 +/- 4, and -56 +/- 5 mV, respectively. In contrast the potential difference of protoscoleces incubated in 1:2 diluted normal human serum showed a significant variation (P < 0.001), reaching -10 +/- 6 mV after 30 min, and the median depolarization time was estimated to be 21 +/- 3 min. The capacity of normal human serum to depolarize the tegumental membrane of protoscoleces was abolished by treatment at 50 degrees C during 20 min or by 10-fold dilution. In addition, protoscoleces incubated in 1:10 diluted hydatid human serum plus 1:10 diluted normal human serum or Factor B inactivated normal human serum showed a significantly faster depolarization (0.01 < P < 0.02 and P < 0.001, respectively): the potential difference reached -13 +/- 5 mV after 15 min and the median depolarization times were 9 +/- 5 and 5 +/- 3 min, respectively. Our results suggest that following the time course of the potential difference is a useful tool for studying complement activation in the host-parasite interface and they show that the tegumental membrane of protoscoleces can activate the alternative pathway of human complement. PMID- 1426131 TI - Plasmodium falciparum: the human agglutinating antibody response to the infected red cell surface is predominantly variant specific. AB - There is mounting evidence that an important component of the host-protective immune response to Plasmodium falciparum is the antibody response to the altered surface of the infected erythrocyte. The nature of these surface changes and the responses to them have been difficult to analyse because of the diverse nature of the parasite-derived neoantigens (PDN) expressed, because of the additional presence of modified host determinants, and because of the lack of monospecific reagents. We have studied the reactivity of field isolates and laboratory clones with pooled or individual sera using a novel approach which obviates the need for specific antibody. We see marked diversity in PDN but in contrast to previous studies, we also find that the predominant agglutinating antibody response in humans is variant specific. Antibodies which cross-react between different serotypes are rare and react only with a subset of PDN types. These results have implications for mechanisms underlying the development of acquired immunity to P. falciparum. PMID- 1426132 TI - Plasmodium gallinaceum: antibodies to circumsporozoite protein prevent sporozoites from invading the salivary glands of Aedes aegypti. AB - A circumsporozoite protein-specific monoclonal antibody (N2H6D5) was injected into malaria-infected mosquitoes to determine its effect on the sporogonic cycle. After injection of antibody into mosquitoes (100 ng each), positive immunofluorescence (measured on air-dried sporozoites) reactions in hemolymph extracts were observed at a dilution of 1:1000. At 72 hr postinjection the levels dropped to 1:10. Sporozoites coinjected with antibody did not invade the salivary glands. In naturally infected mosquitoes, sporozoites were released over a period of 3 to 4 days. Therefore, mosquitoes were injected twice. The first injection was a day before the beginning of sporozoite release and the second, 2 days later. Sporozoite invasion of the salivary glands was assessed 3 days after the second injection, by microscopic examination of dissected glands. At this stage, all oocysts had completed maturation and released the sporozoites. Salivary gland infections were totally prevented in mosquitoes given two injections of 100 ng N2H6D5. Hence, sustained presence of anti-circumsporozoite antibodies in the hemolymph can render female Aedes aegypti refractory to Plasmodium gallinaceum. PMID- 1426133 TI - Schistosoma mansoni: cloning of a complementary DNA encoding a cytosolic Cu/Zn superoxide dismutase and high-yield expression of the enzymatically active gene product in Escherichia coli. AB - We recently purified a 16-kDa cytosolic Cu/Zn superoxide dismutase (CT Cu/Zn-SOD) from Schistosoma mansoni, a human parasite. Three peptide sequences were obtained, one from the unblocked N-terminal and two from internal peptides which were generated by digestions with trypsin and cyanogen bromide. These sequences were aligned to the corresponding sequences of 19 cytosolic Cu/Zn-SODs from various species. Degenerate oligonucleotides were then designed according to the sequence and the position of each peptide. The oligonucleotides were used to amplify a complete cDNA using the polymerase chain reaction with either adult schistosome total RNA or a cercariae lambda gt11 phage cDNA library as the template. The protein encoded by the cDNA has 153 amino acids with a calculated molecular weight of 15,693. It also has 60-65% homology to 19 cytosolic Cu/Zn-SOD from various species. All of the copper/zinc binding sites and SOD activity sites are conserved. Computer analysis predicts that the Cu/Zn-SOD has a pI value of 6.6, which is very close to the experimental results of IEF analysis (6.0 and 6.3). The entire coding sequence from the cDNA was cloned into a bacterial alkaline phosphatase cytosolic expression vector and a large amount of soluble product was expressed and purified to homogeneity. We compared the bacterially expressed Cu/Zn-SOD with the native enzyme derived from schistosomes and found that they are identical by the following criteria: (1) They focus at the same positions on IEF gels; (2) they form dimers in solution as measured by gel filtration; (3) they have the same unblocked N-terminal sequence; (4) they both are enzymatically active with comparable specific activities. The specific activity of the bacterially derived enzyme was increased somewhat (approximately 10%) by incubation with copper and zinc ions. PMID- 1426134 TI - Plasmodium cynomolgi: the hsp 70 gene. AB - The hsp 70 gene of Plasmodium cynomolgi was isolated and characterized. As expected the gene is highly similar to that of the hsp 70 gene of Plasmodium falciparum (98% at the protein level, 82% at the nucleotide level). Surprisingly, the hsp 70 gene appears to be present in a single copy in all the P. cynomolgi strains tested, a finding that has implications for the parasite's ability to undergo a heat shock response. PMID- 1426135 TI - Schistosoma mansoni: control of hepatotoxicity and egg excretion by immune serum in infected immunosuppressed mice is schistosome species-specific, but not S. mansoni strain-specific. AB - Immunosuppressed mice infected with Schistosoma mansoni suffer from an acute hepatotoxicity reaction, and they fail to excrete as many parasite eggs as comparably infected immunologically intact control animals. The hepatotoxicity was shown here to be preventable, and egg excretion rates were enhanced, by transfer of serum from donors with chronic S. mansoni infections, but not by serum from donors with heterologous infections of Schistosoma haematobium, Schistosoma bovis, or Schistosoma japonicum. The effects of the transferred sera are considered to be due to specific antibody, but the possibility of cytokine involvement is discussed. A high degree of serological cross-reactivity was found between sera from mice infected with the different schistosome species and unfractionated egg homogenate (SEA) in ELISA. Cross-reactivity of the heterologous sera was, however, reduced against CEF6, a partially purified fraction of S. mansoni eggs that contains the putative hepatotoxin and has serodiagnostic potential. S. mansoni isolates from Puerto Rico, Brazil, Egypt, and Kenya shared similar characteristics with respect to the immune dependence of egg excretion and hepatotoxicity in immunosuppressed mice. The S. mansoni geographic isolates were also indistinguishable serologically, in terms of both the capacity of respective infection sera to neutralize hepatotoxicity and in their capacity to promote egg excretion of the other isolates in vivo. Complete immunological cross-reactivity of the geographically distinct isolates was also observed in ELISA with both CEF6 and SEA. Utilization of CEF6 for serodiagnosis of schistosomiasis mansoni is therefore unlikely to be restricted by geographical considerations. PMID- 1426136 TI - Plasmodium chabaudi AS: erythropoietic responses during infection in resistant and susceptible mice. AB - The course of anemia and the erythropoietic response in the bone marrow, spleen, and blood were studied during Plasmodium chabaudi AS infection in resistant C57BL/6 (B6) and susceptible A/J (A) mice. Infections in B6 mice were characterized by moderate levels of both parasitemia and anemia and survival. In contrast, A mice experienced high parasitemia, severe anemia, and high mortality rates. During the period of anemia, erythropoiesis, as measured by in vivo 59Fe incorporation, was significantly more depressed in bone marrow and more increased in the spleen in resistant B6 mice. The increase in splenic 59Fe incorporation was a function of the size of the spleen. Bone marrow CFU-E were decreased to 50% of control in both strains, while splenic CFU-E were increased twofold greater in B6 mice compared to those in A mice. However, the absolute numbers of CFU-E per spleen in the two strains were not significantly different during peak parasitemia. Bone marrow BFU-E were transiently increased before peak parasitemia whereas splenic BFU-E peaked during peak parasitemia. A mice had significantly lower numbers of BFU-E per spleen on all days except at peak parasitemia. The frequency of blood-borne BFU-E and plasma erythropoietin titers was increased earlier and to a greater extent in A mice. These results suggest that an impaired amplification of late-stage splenic erythropoiesis may be an important determinant in the severity of anemia and lethality of infection with P. chabaudi AS in A mice. Moreover, these results demonstrate that the defective amplification of splenic erythropoiesis in A mice is neither caused by a defect in the mobilization of BFU-E from the bone marrow to the spleen nor caused by a defect in erythropoietin production. PMID- 1426137 TI - Nitric oxide-mediated cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. AB - Macrophages collected from BCG-infected mice or exposed in vitro to interferon gamma plus lipopolysaccharide developed a cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. This trypanostatic activity of activated macrophages was inhibited by addition of N-monomethyl-L-arginine, an inhibitor of the L-arginine-nitric oxide (NO) metabolic pathway, indicating a role for NO as the effector molecule. Contrary to trypanosomes treated with N2gas, trypanosomes treated with NO gas did not proliferate in vitro on normal macrophages. Compared to mice infected with control parasites, mice infected with NO-treated parasites had decreased parasitemias in the first days postinfection and had a prolonged survival. Addition of excess iron reversed the trypanostatic effect of both activated macrophages and NO gas. These data show that activated macrophages exert an antimicrobial effect on T.b. gambiense and T.b. brucei through the L-arginine-NO metabolic pathway. In trypanosomes, NO could trigger iron loss from critical targets involved in parasite division. The participation of this effector mechanism among the other immune elements involved in the control of African trypanosomes (antibodies, complement, phagocytic events) remains to be defined. PMID- 1426138 TI - Plasmodium berghei: sporozoites are sensitive to human serum but not susceptible host serum. AB - Human complement was activated by rodent malaria, Plasmodium berghei, sporozoites through the alternative pathway, as revealed by C3 deposition on sporozoites using the fluorescent antibody technique. Sporozoites exposed to fresh human serum decreased in infectivity to HepG2 cells, but those exposed to heated or C3 deficient human serum showed normal infectivity to HepG2 cells. In contrast, C3 deposition was not observed on the sporozoites treated with mouse or rat serum even in the presence of specific polyclonal anti-sporozoite antibody. However, following treatment with trypsin (250 micrograms/ml), 81% of salivary gland sporozoites and 49% of oocyst sporozoites became reactive with mouse serum, and reactive sporozoites deposited mouse C3 on their surface in the presence of 30 mM EGTA and 1 mM Mg2+ without antibody. Concomitantly some sporozoites lost reactivity to anti-circumsporozoite protein monoclonal antibody. These results suggest that P. berghei sporozoites possibly express surface molecules that regulate the complement activation pathway of susceptible hosts but not of nonhosts, and that the putative structures consist of protease-sensitive molecule(s) which are closely associated with the circumsporozoite protein. PMID- 1426139 TI - Inhibition of IgM antibody-mediated aggregation of Trypanosoma gambiense in the presence of complement. AB - This paper deals with the immune reaction between Trypanosoma gambiense and monoclonal IgM mouse antibody at equivalence with or without rabbit complement. Antibody-mediated trypanosome clumps formed in the absence of complement, and were readily dissociated by complement to become free. In the presence of complement, on the other hand, T. gambiense were not aggregated by the antibody. Free parasites adhered readily to cultured peritoneal macrophages. Complement mediated dissociation of the clumped trypanosomes in the equivalence area released a large number of previously bound surface antigens. These antigens were capable of binding again to fresh IgM antibody. Experimental results further indicated that the complement system caused a functional alteration, changing the multivalent nature of the IgM antibody in the immune complex into a univalent one. This phenomenon is of great advantage to the infected host in clearing pathogens in vivo, as it allows more antibodies to attach to trypanosomes and subsequently initiate complement activity. PMID- 1426140 TI - Positive and negative inotropic effects of carbachol on the embryonic chick atrium. AB - The effect of carbachol on twitch tension of atrial preparations from chick embryos of different incubation ages (3-14 days) was studied. At every age carbachol evoked negative (at low concentrations) and positive (at higher concentrations) inotropic responses. Maximal response values for both effects increased with age; in 3- and 5-day atria the positive inotropic response prevailed. The muscarinic antagonist pirenzepine inhibited the positive (on 5-day atria) and negative (on strips of 14-day atria) inotropic effects of carbachol with pA2 values of 6.8 and 8.0, respectively, suggesting that muscarinic receptors mediating these effects belong to different receptor subtypes. PMID- 1426141 TI - Stimulation of polydnavirus replication by 20-hydroxyecdysone. AB - During oviposition the endoparasitic wasp Campoletis sonorensis, introduces a polydnavirus into parasitized insects where viral gene expression is required for endoparasite survival. The polydnavirus is integrated into wasp chromosomal DNA and replicates only in the ovary. Ecdysteroids regulate the developmental expression of many insect genes and may regulate polydnavirus replication. Direct verification of viral replication was performed by dot blot hybridization and by amplifying DNA sequences containing the viral integration site; this 'junction' fragment cannot be amplified from integrated virus. Thoracic ligations and in vitro ecdysteroid treatments of wasp ovaries support the hypothesis that polydnavirus DNA replication is regulated by ecdysteroid during parasite development. PMID- 1426143 TI - Endogenous synthesis of peptidoglycan in eukaryotic cells; a novel concept involving its essential role in cell division, tumor formation and the biological clock. AB - Degradation products of peptidoglycan, the universal bacterial cell wall constituent, were previously found in animal tissues and urine. Reassessment and quantitative analysis of available data lead to an original concept, i.e. that eukaryotic cells synthesize peptidoglycan. We present a model in which this endogenously synthesized peptidoglycan is essential for the processes of eukaryotic cell division and sleep induction in animals. Genes for peptidoglycan metabolism, like those for lysine biosynthesis in plants, are probably inherited from endosymbiotic bacteria, the ancestors of mitochondria and chloroplasts. Corollaries of this concept, i.e. roles for peptidoglycan metabolism in tumor formation and in the biological clock, are supported by abundant evidence. We propose that many interactions between bacteria and eukaryotes are conditioned by their common genetic heritage. PMID- 1426142 TI - Perforin and its role in T lymphocyte-mediated cytolysis. AB - The killing mediated by cytotoxic T lymphocytes (CTL) represents an important mechanism in the immune defence against tumors and virus infections. The lytic mechanism has been proposed to consist of a polarized secretion of granule-stored molecules, occurring on effector-target cell contact. By electron microscopy, membrane deposited, pore-like lesions are detected on the target cell membrane during cytolysis by CTL. These structures resembled strikingly pores formed during complement attack. Granules of CTL isolated by nitrogen cavitation and Percoll gradient centrifugation were shown to retain cytotoxic activity. Further purification of proteins stored in these granules led to the discovery of a membranolytic protein named perforin which was capable of polymerizing into pore like structures. In addition to this cytolytic protein, a set of serine esterases was found as well as lysosomal enzymes and proteoglycans, whose function are not yet clearly defined. The role of perforin in the cytotoxic process is currently being explored by ablating the active gene in mice. PMID- 1426144 TI - Intercellular communication in smooth muscle. AB - The functioning of a group of cells as a tissue depends on intercellular communication; an example is the spread of action potentials through intestinal tissue resulting in synchronized contraction. Recent evidence for cell heterogeneity within smooth muscle tissues has renewed research into cell coupling. Electrical coupling is essential for propagation of action potentials in gastrointestinal smooth muscle. Metabolic coupling may be involved in generation of pacemaker activity. This review deals with the role of cell coupling in tissue function and some of the issues discussed are the relationship between electrical synchronization and gap junctions, metabolic coupling, and the role of interstitial cells of Cajal in coupling. PMID- 1426146 TI - Bioaccumulation processes in ecosystems. AB - The fate of environmental pollutants--the various isotopes of elements, and inorganic or organic compounds--is a fundamental aspect of ecology and ecotoxicology, and bioaccumulation is a phenomenon often discussed in this context. Human activities have drastically altered natural concentrations of many substances in the environment and added numerous new chemicals. An understanding of the processes of bioaccumulation is important for several reasons. 1) Bioaccumulation in organisms may enhance the persistence of industrial chemicals in the ecosystem as a whole, since they can be fixed in the tissues of organisms. 2) Stored chemicals are not exposed to direct physical, chemical, or biochemical degradation. 3) Stored chemicals can directly affect an individual's health. 4) Predators of those organisms that have bioaccumulated harmful substances may be endangered by food chain effects. While former theories on the processes of bioaccumulation focused on single aspects that affect the extent of accumulation (such as the trophic level within the food chain or the lipophilicity of the chemical), modern theories are based on compartmental kinetics and the integration of various environmental interactions. Concepts include results from quantitative structure-activity relationships (QSAR), pharmacokinetics, ecophysiology and general biology, molecular genetic aspects and selection, and finally the structure of communities and man-made alterations in them. PMID- 1426147 TI - A study of granulated metrial gland cell differentiation in pregnant, macrophage deficient, osteopetrotic (op/op) mice. AB - A population of uterine natural killer (NK) cells, commonly called granulated metrial gland (GMG) cells, differentiates in the mouse uterus during normal pregnancy. Little is known regarding the process of differentiation of GMG cells or of other NK cell subsets. It has been suggested that macrophage precursors, under the combined influences of the cytokine growth factors colony stimulating factor-1 (CSF-1) and interleukin-2, become NK-cell like in morphology, pattern of target cell lysis and surface antigen phenotype. Mice expressing the mutation osteopetrosis (op/op) are unable to produce the cytokine CSF-1. To determine whether CSF-1 is required for the successful differentiation of uterine NK cells, implantation sites in pregnant, op/op mice were studied histologically. GMG cell differentiation appeared to progress normally in op/op mice studied between days 7 and 14 of gestation. Thus, the growth factor CSF-1 is not required for differentiation of the uterine NK cell subset known as GMG cells and probably GMG cells do not differentiate from macrophage precursor cells which are deficient in op/op mice. PMID- 1426145 TI - Human slow wave sleep: a review and appraisal of recent findings, with implications for sleep functions, and psychiatric illness. AB - Recent findings concerning human slow wave sleep (hSWS-stages 3 + 4; delta EEG activity) are critically reviewed. Areas covered include the significance of the first hSWS cycle; hSWS in extended sleep; relationship between hSWS, prior wakefulness and sleep loss; hSWS influence on sleep length; problems with hSWS deprivation; influence of the circadian rhythm; individual differences in hSWS, especially, age, gender and constitutional variables such as physical fitness and body composition. Transient increases in hSWS can be produced by increasing both the quality and quantity of prior wakefulness, with an underlying mechanism perhaps relating to the waking level of brain metabolism. Whilst there may also be thermoregulatory influences on hSWS, hypotheses that energy conservation and brain cooling are major roles for hSWS are debatable. hSWS seems to offer some form of cerebral recovery, with the prefrontal cortex being particularly implicated. The hSWS characteristics of certain forms of major psychiatric disorders may well endorse this prefrontal link. PMID- 1426148 TI - Mechanoelectrical transduction, ion movement and water stasis in uromodulin. AB - Mechanical movement of a column of the urinary glycoprotein uromodulin modulates an applied voltage. This change is a property of the glycoprotein and its interaction with the walls of the container and is related to its capacitance. The voltage modulation is not accompanied by changes in rotationally restricted water as has been reported for hyaluronic acid. Diffusion experiments with tritiated water also support the hypothesis that uromodulin acts as a water barrier, but allows ion movement. PMID- 1426149 TI - The effect of shock on blood oxidation-reduction potential. AB - Oxidation-reduction (redox) potential measurements were made in the blood of rabbits subjected to hemorrhagic shock followed by treatment with a mild oxidizing agent (albumin). Control redox potential reading corrected for pH was 8.8 +/- 1.3 millivolts (mV) in arterial blood (A) and -18.0 +/- 2.0 mV in venous blood (V). This A-V difference indicated that hydrogen equivalents coming from muscle and other tissues were partially consumed in the lungs. A 20-mV drop on the V and a 13 mV on the A side was seen after shock. This did not fully return to control 2 h after return of the shed blood. Infusion of 2 g of albumin/kg/h raised the V redox potential to control, but it returned to untreated levels when the albumin was discontinued. The reductive load imposed on the animal by shock appeared to be large and not readily reversed by reperfusion or by the quantity of albumin given. Thus, it may be concluded that cellular respiration had not been adequately restored. This reductive load may impede recovery by suppression of cellular respiration and other cell and organ functions. PMID- 1426150 TI - The presence of free D-serine, D-alanine and D-proline in human plasma. AB - Twelve neutral free amino acids, i.e. serine, threonine, glutamine, asparagine, alanine, proline, methionine, tyrosine, valine, leucine, isoleucine and phenylalanine, were surveyed for the presence of D-enantiomers in plasma samples from patients with renal diseases and from normal subjects. D-serine, D-alanine and D-proline were found in the patient's plasma. The highest concentrations (D/L ratio) of D-serine, D-alanine and D-proline were 0.2362, 0.2087 and 0.0986, respectively. The sum of the contents of the three D-amino acid was shown to be present in the plasma proteins. PMID- 1426152 TI - Influence of flupirtine, a novel nonopioid analgesic agent on somatosensory evoked potentials in rats. AB - The effect of flupirtine, a novel nonopioid analgesic, on somatosensory evoked potentials (SEP) was investigated in anesthetized rats. Primary somatosensory potentials were evoked in the cerebral cortex by stimulation of the skin of the whiskery part of the face. Flupirtine injected i.p. dose-dependently prolonged the latency and reduced the amplitude of SEP with ID50-values of 5.4 mg/kg (2.6 9.3 mg/kg) and 7.9 mg/kg (3.9-13.8 mg/kg), respectively. This effect of flupirtine (10 mg/kg, i.p.) on the latency and the amplitude of SEP, did not change when naloxone (1 mg/kg, i.p.) was given before flupirtine. The results indicate that the analgesic flupirtine decreases the primary somatosensory evoked potential by diminishing the excitability of cortical neurons. Opioid mechanisms are not involved. PMID- 1426151 TI - The effect of ascorbic acid on cadmium accumulation in guinea pig tissues. AB - Accumulation of cadmium in organs of guinea pigs after subchronic oral cadmium treatment (1 mg Cd/animal/24 h) was in the following order: kidneys > liver > heart > testes > brain. The preventive effects of high doses of ascorbic acid (AA) against cadmium deposition were more pronounced in the testes, heart and brain, and in the kidney only after short-term cadmium treatment. Ascorbic acid had no protective effect on cadmium accumulation in the liver. PMID- 1426153 TI - Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats. AB - To study the effect of a sudden loss of body weight on the beta-cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum. PMID- 1426154 TI - Dehydroepiandrosterone sulfate-binding sites in plasma membrane from human uterine cervical fibroblasts. AB - Dehydroepiandrosterone sulfate (DHA-S) plays a critical role in cervical dilatation at labor. Incubation of cervical fibroblasts with [3H]DHA-S caused a rapid and saturable increase in cellular radioactivity: an apparent equilibrium was reached by 2 min. There was no detectable conversion of DHA-S into DHA or oestradiol. When the fibroblasts loaded with [3H]DHA-S were homogenized and fractionated, the specific radioactivity in the plasma membrane fraction was enriched approximately 8- to 9-fold compared with the whole homogenate; only low amounts of radioactivity were observed in the other subcellular fractions. The binding of DHA-S to plasma membrane preparations showed saturation kinetics with an apparent equilibrium dissociation constant (Kd) of 12 nM, and the binding capacity (Bmax) was calculated to be 1.25 fmol/mg protein. Neither DHA nor oestrone sulfate affected [3H]DHA-S binding to the plasma membrane. The plasma membranes of skin fibroblasts did not show specific binding sites for DHA-S. These findings demonstrate the presence of specific binding sites for DHA-S in the plasma membrane of cervical stroma cells. The fetal adrenal steroid may exert its action on cervical ripening at least in part through membrane-associated binding sites, or receptors. PMID- 1426155 TI - Evidence that protein kinase-A, calcium-calmodulin kinase and cytoskeletal proteins are involved in osteoclast retraction induced by calcitonin. AB - Calcitonin is a direct inhibitor of osteoclastic activity. Osteoclast retraction is readily induced by calcitonin and it is possible that calcitonin-induced inhibition of bone resorption is in part due to this effect. However, little is known of the mechanisms of this action. In these studies, we have investigated the intracellular signalling pathway of calcitonin-induced osteoclast retraction using cultures of freshly isolated rat osteoclasts. The spread area occupied by single Giemsa-stained rat osteoclasts was measured in vitro by a computer imaging analysis system and used as a quantitative parameter for calculating the degree of osteoclast retraction in response to various agents. Our results show that cAMP may be an important second messenger in the reaction of osteoclasts to calcitonin. Moreover, both protein kinase-A and calcium/calmodulin-dependent protein kinase are involved in the osteoclast retraction induced by this hormone, while cytoskeletal proteins are required for the process to occur. PMID- 1426156 TI - Ultrastructural alterations in mouse capillary blood vessels after experimental injection of venom from the snake Bothrops asper (Terciopelo). AB - Histological and ultrastructural alterations in capillary blood vessels were studied at various time intervals after im injection of 50 micrograms of Bothrops asper snake venom in mouse gastrocnemius muscle. Hemorrhage was observed as early as 5 min after envenomation, as abundant erythrocytes appeared in the interstitial space. Ultrastructural observations revealed two different patterns of pathological changes: in the majority of damaged capillaries, endothelial cells had blebs and cytoplasmic projections pinching off to the lumen. This phenomenon was observed together with a decrease in the number of pinocytotic vesicles, with endothelial cells becoming very thin. As an apparent consequence of this process, some endothelial cells had evident gaps in their continuity. In addition, basal laminae surrounding these capillaries were altered and discontinuous. Other endothelial cells underwent a morphologically different process of degeneration, characterized by swelling of the endoplasmic reticulum and of the cytosol. These cells had a diffuse appearance and their basal laminae were discontinuous or absent. No major changes in the intercellular junctions were noticed in damaged endothelial cells. Samples obtained 30 and 60 min after venom injection were devoid of normal capillaries in many areas, and only diffuse remnants of their structure were found. Many altered capillaries had platelet aggregates and fibrin, the latter also being observed in the interstitial space. It is concluded that B. asper venom induces rapid and drastic pathological effects on capillaries leading to hemorrhage per rhexis i.e., erythrocytes probably escape through gaps in damaged endothelial cells and not through widened intercellular junctions. PMID- 1426158 TI - Normal elastin content of aorta in bovine Marfan syndrome. AB - Samples from the ascending aortae from two calves affected by bovine Marfan syndrome were subjected to biochemical analyses of the connective tissue and were compared to age-matched controls. Elastin was extracted from the aortic samples with 5 M guanidine-HCl, bacterial collagenase digestion, and dithiothreitol reduction. Amino acid analysis revealed that desmosine and isodesmosine levels were the same in Marfan calves as in control animals. Gravimetric measurements of elastin, amino acid composition, soluble protein, and uronic acid values also showed no significant difference between Marfan and control tissue. In contrast to elastin, collagen in aortae of Marfan calves was significantly higher than the mean of several controls. These findings, along with other observations of this animal model, support the conclusion that the microscopic and biochemical lesions of aortic elastin in bovine Marfan syndrome likely result from defective microfibrillar metabolism. Absence of cystic medial necrosis in bovine Marfan aortae may explain normal elastin content in the animal model. PMID- 1426157 TI - Increased platelet, but unaltered fibrinogen, accumulation in experimental thrombi in alloxan-induced diabetic rabbits. AB - Platelets from diabetic humans and animals have been found previously to be hypersensitive to agonists, including thrombin, in vitro but it is unclear if this hypersensitivity also occurs in vivo and leads to a greater thrombotic tendency. In the present study, the effect of diabetes was examined on thrombus formation and vessel wall responses which result from continuous intimal injury induced by indwelling aortic catheters in rabbits. Platelet and fibrin(ogen) associated with the thrombus and damaged aortae were examined. Control or alloxan induced diabetic rabbits (9-12 months after initial treatment) were injected with 51Cr-labeled autologous platelets and 125I-labeled fibrinogen (prepared from control rabbits) before insertion of indwelling aortic catheters. The anesthetized rabbits were perfused-fixed after 20 hr or 4 days. The dry weight of thrombus that formed was determined and platelet and fibrin(ogen) accumulation in thrombi and on injured aortae were calculated from the associated 51Cr and 125I, respectively. In diabetic rabbits, more platelets accumulated in the thrombi which formed after either 20 hr or 4 days, although the weight of thrombus and net fibrin(ogen) incorporation into the thrombus were not different from corresponding control rabbits. Net platelet and fibrin(ogen) association with the injured aortae were not different between control and diabetic rabbits. It is likely that the increased platelet accumulation in arterial thrombi in diabetic rabbits which results from continuous injury to aortae is a consequence of hypersensitivity of these platelets to thrombin generated in the thrombus and at the sites of vessel injury. PMID- 1426159 TI - Pathology of chemically induced chronic active hepatitis in mice. AB - Female Swiss mice were treated for 24 weeks, with 3-hydroxy-4-pyrone (Py) added to their powdered diet at 0.5% (wt/wt), and the effects of this agent on the liver were examined. Serum transaminases (especially GPT) rose continuously, while the GOT/GPT ratio remained at approximately 1.0 throughout the study period. The characteristic changes found from 8 weeks onward were piecemeal necrosis and bridging necrosis of the hepatocytes with dense lymphocytic infiltration. Proliferation of collagen fibers in the portal tracts and formation of narrow fibrous septa dividing the lobules into pseudolobules were also noted from 12 weeks onward. A large number of the infiltrating lymphocytes were identified as T cells by immunohistochemical and electron microscopic studies. These lymphocytes often surrounded or were closely attached to degenerating hepatocytes. Focal apoptosis and necrosis accompanied by a granulomatous reaction of the centrilobular hepatocytes were noted as early changes in the liver. Our findings indicate that the hepatic changes produced in mice by long-term Py administration have characteristics in common with those of human chronic active hepatitis. Immunological cytotoxic mechanisms, especially T cell-mediated ones, appear to play an essential role in the development of hepatic lesions in this murine model of chronic active hepatitis. PMID- 1426160 TI - Cytoskeleton-dependent surface blebbing induced by the polar solvent N methylformamide. AB - In vivo and in vitro studies performed on the polar solvent N-methylformamide (NMF), as well as on its association with chemotherapeutic agents or X rays, have clearly demonstrated that this compound is capable of inducing changes in biological characteristics of tumor cells, e.g., cell differentiation. However, the mechanism of action of NMF is far from being elucidated. Hence, in order to better clarify such a mechanism an in vitro study was carried out by using mouse fibroblasts in primary culture (MEF) and human melanoma cultured cells (M14). Results obtained by immunocytochemical and ultrastructural methods with doses of NMF ranging from 0.1 to 7% are reported here. As a general rule, a different sensitivity (in terms of cytopathologic changes induced by NMF) was found between the cell types considered. In fact, melanoma cells appeared to be highly susceptible to the action of the drug, undergoing severe morphological modifications represented mainly by a reversible dose and time-dependent cell rounding and surface blebbing. In contrast, NMF-induced injury in MEF cells was characterized mainly by a simple retraction of the cell body. A cytochemical analysis of the expression of certain membrane antigens (e.g., glycoproteins, epidermal growth factor receptor, B2 microglobulin) in NMF-treated M14 cells undergoing blebbing was also carried out. A randomly distributed labeling of such molecules was observed. Accordingly, freeze-fracturing electron microscopic analysis also displayed a random distribution of intramembrane particles over the plasma membrane. When subcellular changes induced by the drug were investigated, a remarkable modification of cytoskeletal components was detected in both cell types. In particular, cross-linked actin microfilament bundles were easily observed in NMF-exposed MEF cells. Finally, when different experimental conditions which perturb calcium ion homeostasis or restore protein thiol group reduced state were analyzed, a noticeable impairment of the blebbing phenomenon was observed. Thus, a target effect of NMF on the microfilament system, probably leading, in turn, to several subcellular changes and cell surface blebbing, can be hypothesized. Such a cytoskeletal element-dependent cytopathology appears to be related to changes of the oxidized state of such molecules as well as to calcium ion perturbations. PMID- 1426162 TI - Prevalence of hepatitis B markers in the population of Catalonia (Spain). Rationale for universal vaccination of adolescents. AB - The prevalence of hepatitis B markers was determined in a representative sample of the general population of Catalonia (Spain). HBsAg was found in 0.5% of children (less than 15 years of age) and in 1.7% of adults (more than 15 years of age), and anti HBs in 1.6% and 18%, respectively. Age-specific prevalence for both markers showed a low risk for hepatitis B before puberty, and a progressive rise since adolescence, suggesting that perinatal transmission and horizontal transmission in children are relatively uncommon in Spain. Prevalence of hepatitis B markers was significantly higher among subjects with low education level, residing in an urban area and born outside Catalonia, but in the stratified analysis, a statistical significant difference was only maintained in the prevalence of HBV markers between those who live in urban and rural areas, and between those who were born outside Catalonia and in Catalonia. These data may be used as a basis for a strategy of hepatitis B prevention in Spain which include universal vaccination of adolescents, passive-active immunization of newborns to HBsAg positive mothers and vaccination of susceptible adults subjects from high-risk groups. PMID- 1426161 TI - A descriptive study of pregnant women with gallstones. Relation to dietary and social habits, education, physical activity, height, and weight. AB - Five hundred and twelve women attending the antenatal clinic of the Rotunda Hospital of Dublin were studied by means of abdominal real time ultrasound (US) scanning to establish some of the characteristics of those subjects found to be gallstone-positive, compared to the gallstone-negative control population. Coffee, tea and sucrose consumption, dietary fats, attendance at fast-food restaurants, education, cigarette smoking, alcohol, and physical activity did not show any substantial differences between the two groups, while there was a significantly higher prevalence of cholelithiasis in women who had been dieting and in overweight subjects. PMID- 1426163 TI - Chlamydial genital infections and laparoscopic findings in infertile women. AB - Several studies have shown that previous chlamydial genital infection, reflected by serological markers, is strongly associated with tubal damage leading to tubal infertility. In 105 women undergoing laparoscopy, multiple samples were collected from the lower (urethra and cervix) and upper (endometrium, peritoneal fluid, tubal lumen) genital tract, in order to isolate Chlamydia trachomatis in cell culture. Chlamydia trachomatis was isolated from at least one site in 13 (30.9%) of 42 infertile women with tubal infertility, in 5 (12.1%) of 41 women with unexplained infertility, in 1 of 4 women affected by acute salpingitis and in 1 (5.5%) of 18 women with endometriosis or uterine malformations. The latter group was the control group. Thirteen (65%) of the 20 positive women harboured Chlamydia trachomatis in their upper genital tract alone and 16 women were positive in one or both tubes. Only one of the positive women showed laparoscopic signs of acute pelvic infection. Four of the 5 positive women with unexplained infertility harboured Chlamydia trachomatis in the tubal lumen. This study confirms that chlamydial infection is strongly associated with tubal damage. It suggests that cervical cultures are inadequate for excluding a tubal infection and that chlamydial colonization of the tubal mucosa is possible in the absence of symptoms and laparoscopic signs of active infection. PMID- 1426164 TI - Long-term immunogenicity safety and efficacy of a recombinant hepatitis B vaccine in healthy adults. AB - Two hundred healthy adults seronegative for HBV markers received three 10 or 20 mcg injections of a vaccine formulated from HBsAg produced by a recombinant strain of the yeast Saccharomyces cerevisiae. The vaccine was administered intramuscularly at 0, 1, and 6 months in the deltoid region. The seroconversion rates, expressed in GMT/IU/1 were determined at 1, 2, 6, 7, 12, 24, 36 and 48 months following the initial injection. No severe or serious adverse reactions attributable to the HB vaccines were observed in any subject. The seroconversion rates following the 20 mcg dose of recombinant vaccine were always higher than those observed after the 10 mcg dose, but the differences were not statistically significant. Also the GMT values were lower after the 10 mcg dose of vaccine. Females showed a higher anti-HBs response than males; an age-dependent effect was observed in the anti-HBs response as regards both the percentage of responders and the antibody concentrations in the serum. No adverse reactions to the vaccine were observed. The rDNA vaccine did not induce a response to yeast-derived impurities and did not increase anti-yeast IgE antibody titres. The results of this study have shown that the Amgen rDNA vaccine is safe and clinically well tolerated, and that it provides protection against infection and disease. A vaccination dose of 20 mcg appears more advantageous for healthy adult subjects. PMID- 1426165 TI - Job absenteeism and arterial hypertension: results of a hypertension control program. AB - This study reports the findings of one of the stages of a programme for the detection and control of arterial hypertension, started in 1980 in an automobile company with a workforce of 9,782. In the initial screening, 522 hypertensive males were found using epidemiological criteria and 206 of these fulfilled the criteria of definite hypertension. The objective of this study consisted of evaluating, 9 years after the start of the program, the indirect cost in terms of the reduction in the morbidity indicator-temporary work incapacity (TWI). Analysis is based on a comparison of the prevalence of hypertension in the population when the program was begun (6%) and in 1989 (9.8%). It can be observed that the TWI rate of the hypertensive population was significantly higher than that of the rest of the workforce, and that this remained true for the reference group (RG) hypertensives a year after the study was initiated. In contrast, the intervention group (IG) showed significantly lower TWI levels, not only in comparison with the RG but also with the rest of the workers. The estimated reduction in TWI for 1989 was 4.500 days/year, which corresponds to an estimated saving of 76.500.000 pesetas/year. PMID- 1426166 TI - Serological response of tuberculosis patients to antigen 60 of BCG. AB - Two ELISA tests (IgG and IgM) for the serodiagnosis of tuberculosis, both based on antigen 60 (A60) of M. bovis BCG, were applied to 1,644 controls and patients to analyse the immune response in different forms of this infectious disease. Out of 200 healthy individuals, 148 being tuberculin--positive BCG-vaccinated adults, only 10 contacts--nurses of the pneumology department and laboratory technicians of the mycobacterial laboratory--were found positive for anti-A60 IgG. One quarter of hospitalized patients affected by non-tuberculous pneumopathies (194 in total) were found weakly positive for anti-A60 IgG. We suppose that these positive cases have suffered from inapperant infections and are in a "persistent state". Out of 344 cases of primary pulmonary tuberculosis, 88% were positive for anti-A60 IgG and 75% for the corresponding IgM. Among 97 cases of primary extra pulmonary tuberculosis, 94% were found IgG positive and 33% IgM positive. The difference between active and inactive post-primary (chronic) tuberculosis was striking: about 100% of both pulmonary and extra-pulmonary cases (367 altogether) had high titers of anti-A60 IgG but IgM positivity was observed in only 15% of the cases, whereas in inactive and quiescent noncavitary tuberculosis (442 cases), 57% of the patients were weakly positive for anti-A60 IgG and none were positive for IgM. Kinetics of synthesis of anti-A60 IgG and IgM were analysed in primary and post-primary (chronic) active tuberculosis. The IgM tracing immune response to A60 was shorter and lower during primary tuberculosis as compared to post-primary tuberculosis. Our findings point to the high prognostic value of the A60- ELISA test for tuberculosis. Anti-A60 IgM mark initial stages of the disease or reactivation processes whereas anti-A60 IgG last longer than IgM and provide an evaluation of the intensity of the infectious process. Repeated serological tests allow monitoring of the course of the infection and the efficacy of therapy. The test is negative in healthy BCG-vaccinated persons (tuberculin positive) and healed tuberculous infection cases. The combined use of both IgG and IgM tests helps in the correct diagnosis of "false positive" cases. PMID- 1426167 TI - Evaluation of an immunoenzymatic test (ELISA) for the diagnosis of leptospirosis in Italy. AB - An enzyme-linked immunosorbent assay (ELISA) was assessed to detect in humans IgM and IgG against the main serogroups/serovars of Leptospira present in Italy. Sonicated antigens from strain Wijnberg, serogroups Icterohaemorrhagiae and Riccio 2, serogroup Australis, were used in ELISA and the results were compared to microagglutination test (MAT). IgM were confirmed to be the predominant class of antibodies; the total sensitivity obtained by Wijnberg/ELISA with the sera of patients infected by different serogroups was 81.5% in relation to MAT, better sensitivity was achieved by the use of Riccio 2/ELISA; no reaction occurred with the control sera. Cross-reactivity was noted with some sera of patients with Lyme disease (IgM) and with few sera of patients with autoimmune disease (IgM and IgG). To improve the sensitivity of the ELISA both antigens Wijnberg and Riccio 2 must be employed in the immunoenzymatic assay, since serogroup Australis must be considered as a new emerging serogroup causing human leptospirosis in our country. PMID- 1426168 TI - Occurrence of bacteremia in hematologic patients. AB - In the present study we reviewed eighty-six episodes of bacteremia occurred in 60 neutropenic patients and thirty-one episodes occurred in 30 non-neutropenic patients. Twenty-four out of 60 neutropenic patients suffered from multiple episodes of bacteremia, while only one out of 30 non-neutropenic patients presented multiple episodes. In neutropenic patients, 29 episodes of bacteremia were polymicrobial, whereas only one non-neutropenic patient had polymicrobial bacteremia. Intravascular catheters were the most common source of bacteremia (23.2%) in neutropenic patients, as compared with infections of the genito urinary tract (45.1%) among non-neutropenic patients. In both groups, aerobic gram-positive cocci were the microorganisms most frequently isolated (71.6%). Anaerobic microorganisms showed an higher incidence in polymicrobial episodes than in monomicrobial episodes x 2 = 5.39 p = 0.02 OR = 2.97 95% CI (1.2-7.7). PMID- 1426169 TI - Cholesterol and other cardiovascular risk factors in a working population in Ile de-France (France): first results of the PCV-METRA study. AB - In 1989, the French PCV-METRA Group (PCV-METRA = Prevention Cardio-Vasculaire en Medecine du Travail) started a large prospective survey of cardiovascular (CDV) morbidity and mortality and of CVD risk factors, especially cholesterol, in a working population in Ile-de-France, a region including Paris. This report presents the first results of this study, based on a sample of 5758 men and 2603 women, aged 18-65 years. The variables examined included the levels of total cholesterol 1/2 (TC), High-density-lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and the other major CVD risk factors (smoking, sedentary way of life, hypertension, hypercholesterolemia, use of oral contraceptives and familial history of CVD risks). TC and LDL-C significantly increased with age. The changes with age were significantly different in men and women. The levels were similar in both sexes at less than 30 yrs, increased sharply for men after age 30 and were significantly higher in men than in women from 30 to 55 yrs. Beyond 55 yrs, no difference was observed between the two sexes. In contrast, HDL-C was higher in women at all age ranges. In the total sample, 35% of men and 21% of women were hypercholesterolemic (TC > or = 2.4 g/L). Our observations fully confirm and refine previous findings in the US and in other European countries. In addition, a substantial set of data on CVD risk factors for the working population in France, especially for female subjects for whom data are scanty, is now available. PMID- 1426170 TI - HTLV-II among Italian intravenous drug users and hemophiliacs. AB - The seroprevalence of HTLV-I/II was evaluated in 1247 Italian individuals at high risk for HIV infection. The population studied consisted of 985 intravenous drug users (IVDUs), 474 of whom on methadone maintenance and 511 in a therapeutic community, 110 HIV-infected patients in various stages of HIV-related disease and 152 hemophiliacs. Sera were screened for antibody to HTLV-I/II by enzyme immunoassay (EIA) and confirmed by Western blot and radioimmunoprecipitation assay. Confirmed positive samples were further differentiated by EIA using HTLV-I and HTLV-II specific peptides. The overall prevalence of anti-HTLV-I/II was 4.0% in IVDUs, with the highest prevalence (8.2%) among HIV-infected symptomatic patients. None of the hemophiliacs was anti-HTLV-I/II positive, even though 63.1% tested positive for HIV antibodies. The trend of seroprevalence in drug users and the evaluation of possible risk factors demonstrated that HTLV-I/II infection has been present in Italy before the onset of HIV epidemic. The overall seroprevalence showed no significant changes during the 10 year period covered by this survey but correlated with HIV seropositivity, age and duration of drug use. Peptide testing showed that HTLV infection was mainly due to HTLV-II. PMID- 1426171 TI - The association of low socio-economic status in metropolitan Adelaide with maternal demographic and obstetric characteristics and pregnancy outcome. AB - The South Australian perinatal statistics collection for 1988 was used to consider the association of low socio-economic status in metropolitan Adelaide (South Australia) with maternal demographic and obstetric characteristics and pregnancy outcome in 12047 singleton births. Socio-economic status--low, middle or high--was inferred from the socio-economic rating of the postcode of residence. Chi-squared analyses were carried out to test for significant trends in proportions of pregnancy and pregnancy outcome variables across the socio economic groupings. There was trend for the proportions of adverse obstetric and perinatal outcomes to decrease with increasing level of socio-economic status. Logistic regression analysis, adjusted for maternal age, marital status, race, parity and gestational age, confirmed the findings of the trend analyses, namely that mothers from the poor socio-economic areas were at a greater risk for poor pregnancy outcome. These poor outcomes included Apgar scores of less that 7 at both 1 and 5 minutes after birth, delay in onset of regular breathing of 5 minutes or longer; the need for intubation; the use of narcotic antagonists; low birthweight of under 2500 g; the need for special nursey care; and neonatal death. PMID- 1426172 TI - Infection and cancer: current state of art. AB - Empirical evidence of the association of cancer with parasitic and viral infectious agents has been recognized earlier. Today, viruses are thought to account for about 10% of all cancers and they take a central place in experimental cancer research. This area has expanded tremendously with modern molecular biology techniques, the knowledge of gene expression, cellular enzyme and mechanisms of transformation. However, the last proof of causality is not yet available. Serologic, virologic, experimental and protective evidence is needed to confirm the assumptions in this rapidly developing field of research. The prevention of hepato-cellular carcinoma by effective vaccines now available is, in the opinion of the WHO, at least theoretically possible. PMID- 1426173 TI - Condom use and sexual habits of heterosexual intravenous drug users in northern Italy. AB - In order to assess modes of human immunodeficiency virus (HIV) transmission from heterosexual intravenous drug users (IVDUs) to their partners, condom use and sexual habits with both steady and occasional partners were investigated. A total of 349 heterosexual IVDUs (247 men and 102 women) who ignored, at the time of interview, their HIV serostatus were interviewed. Respondents were asked for information on condom use and sexual habits for the three year period prior to the interview. Nearly 40% of IVDUs reported sexual intercourse with both steady partners and occasional partners. Fifty-four percent of their steady partners and 48% of their occasional partners were individuals who did not belong to groups at risk for HIV infection. Anal intercourse with steady partners was reported by 29% of IVDUs and 24% of IVDUs with occasional partners. Condom use during vaginal intercourse was seldom reported: 83% of IVDUs never used a condom with steady partners and 75% did not use one with occasional partners. IVDUs who were 1) unmarried, 2) enrolled in the study after 1986, 3) partners of not at-risk individuals, 4) partners of a foreigner and, 5) aware of their partners HIV seropositivity showed significantly higher, albeit still low, frequencies of condom use with steady partners. Conversely, all these factors seemed to have little impact on condom use with occasional partners. Condom use and sexual habits were similarly reported by HIV-positive and HIV-negative IVDUs. The present study shows that high-risk sexual behaviours among IVDUs are very widespread and it stresses the need for intensive counselling to promote condom use among IVDUs. PMID- 1426174 TI - Proximal femoral fractures: prevalence in different racial groups. AB - This paper describes the methodology and the results of a study performed in Central England. The predominant racial group here is "White European" (Europid). There are smaller numbers of people of Indian origin (Indids) and still smaller numbers of Afro-Caribbean and of Mongolian ancestry (Mongoloids). We found no significant differences in the incidence of hip fractures in the first two groups. The study population was 1600 consecutive patients with proximal femoral fractures (PFF). The difficulties of racial classification are discussed. To elucidate the predisposing factors for PFF, large scale collaborative studies between medical centres in the major European, Asian, African and American conurbations are suggested. Racial burden may be one such factor; osteoporosis may be another. PMID- 1426175 TI - Heredity of asthma in Saudi population. AB - In a cross-sectional study, the prevalence of asthma, hay fever and eczema was studied in 1150 schoolchildren attending school in Jeddah Western region of Saudi Arabia. The family histories of asthma, hay fever and eczema were examined in first degree relatives. The age range of children studied was 7-12 years, with a mean of 9.3 years (47% boys and 53% girls). A self-administered questionnaire was completed by the parents of the child to collect information concerning bronchial asthma, hay fever, and eczema in the target child and family history of respiratory allergy. A detailed family history and personal histories of asthma were available for 1035 Saudi children aged 7-12 years old. The rate of asthma and hay fever were significantly higher among siblings and offspring (cases) compared to their parents (p < 0.001). The results showed a high positive correlation between the relatives of affected children with respect to asthma and hay fever. These findings support the hypothesis that asthma and hay fever may be inherited in the Saudi population, but the mode of inheritance has yet to be determined. PMID- 1426176 TI - Clusters of meningococcal disease in France (1987-1988). AB - We analyzed 814 cases of meningococcal disease notified in 1987 and 1988 to the Ministry of Health. Data were obtained by report forms including informations about possible additional cases among contacts. Coprimary cases (occurring within 24 hours after the index case) and secondary cases (occurring more than 24 hours after index case) were all reviewed. Twenty eight clusters of meningococcal disease were identified involving 65 cases (8% of total cases). Twelve of the 814 cases (1.5%) were coprimary cases of an index case and 25 (3%) were secondary cases. The secondary attack rate was 530/100,000 among household contacts and 31/100,000 among school contacts. Seventy two per cent of the secondary cases occurred in the first week after index case. Thirty-eight percent of the secondary cases occurred in the 15-20 age group as opposed to 15% of single cases. Serogroup A was more often found in coprimary (33%) and secondary cases (17%) than in single cases (6%). In France, prophylaxis of secondary cases is administered to the classroom contacts of a case of meningococcal infection but is not required for the entire school except under epidemic conditions. PMID- 1426177 TI - The protease from Vibrio cholerae nicks arginine at position 192 from the N terminus of the heat-labile enterotoxin a subunit from enterotoxigenic Escherichia coli. AB - It was examined where a protease purified from Vibrio cholerae might nick the heat-labile enterotoxin (LT) A subunit from enterotoxigenic Escherichia coli. LT was digested by the protease and contained a fragment which had the same mobility on SDS-PAGE as that of the A1 fragment of LT digested by trypsin. The biological activity of LT by this protease was also identical to that of LT by trypsin. The amino acid sequence of the N-terminus of the A2-like fragment was Thr-Ser-Thr Gly, which corresponded to the sequence from 193 to 196 of the A subunit. These data suggest that this protease, like trypsin, nicks arginine at position 192 from the N-terminus of the A subunit and that the biological activation of LT by this protease is similar to that by trypsin. PMID- 1426179 TI - Wound botulism: clinical and microbiological findings of an Italian case. AB - A case of wound botulism in a 41-year old man is reported. The patient had accidently been wounded when he fell on an iron bar. Some days later he developed typical clinical manifestations of botulism. Wound botulism was confirmed by detection and quantification of type B botulinal toxin in the serum. Ventilatory supportive care was necessary and botulinal antitoxin was not given. The patient was hospitalized for 30 days and recovery was complete. PMID- 1426178 TI - Legionellosis associated with artesian well excavation. AB - In October 1990 pneumonia due to Legionella pneumophila was diagnosed in two employees working in the area of Apulia, southern Italy, where artesian wells were in construction. Although the exposure to excavation has been associated with Legionnaires' disease, in our investigation the illness occurred only in those employees who were present when the water emerged from the ground under high pressure. On the basis of this report, water appears as the most likely reservoir of the organism and the main route of infection. PMID- 1426180 TI - Congenital cardiac anomalies relative to selected maternal exposures and conditions during early pregnancy. PMID- 1426181 TI - Parental involvement in minors' abortion decisions. AB - In a 1991 study based on a nationally representative sample of more than 1,500 unmarried minors having an abortion, 61% of the respondents said that one or both of their parents (usually the mother) knew about the abortion. Only 26% of the respondents said their father knew about the abortion; furthermore, 57% of the mothers who knew about their daughter's pregnancy did not tell her father. In this study, which was conducted in states without parental involvement laws in effect, about 75% of the parents who knew about the pregnancy had been told by the daughter herself, and the great majority supported their daughter's decision to have an abortion. Among the minors whose parents found out without being told by the minor, 18% said their parents were forcing them to have an abortion and 6% reported physical violence, being forced to leave home or damage to their parents' health. Minors who did not tell their parents were disproportionately older (aged 16 or 17), white and employed. The minors' most common reasons for not telling their parents were wanting to preserve their relationship with their parents and wanting to protect the parents from stress and conflict. Of those who did not tell their parents, 30% had experienced violence in their family, feared that violence would occur or were afraid of being forced to leave home. Among minors whose parents were unaware of the pregnancy, all consulted someone other than clinic staff about the abortion; most frequently, they consulted their boyfriend (89%), an adult (52%) or a professional (22%). PMID- 1426182 TI - Characteristics and attitudes of early contraceptive implant acceptors in Texas. AB - In 1991, shortly after Norplant became available in the United States, 678 women who had received the implant from 17 providers in Texas were surveyed. Forty-five percent of these women were under 21 years old. The majority (56%) had tried the implant because they were dissatisfied with their previous contraceptive method. Forty-four percent of the sample indicated that the implant was one of the first contraceptive methods they had used and that they had only recently decided to prevent unplanned pregnancy. The average number of children per woman was 1.2, and one-third of the sample had had at least one abortion. While 37% of the women said they wanted no more children, 63% said they were using the implant as a spacing method. The reasons for choosing the implant and concerns about it varied according to the user's age, educational level and race or ethnic group. PMID- 1426183 TI - The effect of family planning participation on prenatal care use and low birth weight. AB - Data on approximately 45,000 North Carolina women who gave birth in 1989 and 1990 and received prenatal care in public health facilities were studied to assess the effects in a low-income population of prior family planning services on low birth weight and adequacy of prenatal care. Women who had used family planning services in the two years before conception were significantly more likely than those who had not used such services to have a birth-to-conception interval of greater than six months. They were also more likely to receive early and adequate prenatal care and to be involved in a food supplement program and maternity care coordination. In addition, the family planning participants were less likely than the nonparticipants to be younger than 18 and were somewhat less likely to deliver a low-birth-weight infant. Though the results of this retrospective study must be interpreted with caution because of such factors as self-selection into family planning programs, they suggest that family planning services may improve birth weight and use of prenatal health services among low-income women. PMID- 1426185 TI - Abortion agency offers adoption services. PMID- 1426184 TI - Contraceptive use and sterilization among Puerto Rican women. AB - A comparison of contraceptive use in the early to mid-1980s among married Puerto Rican women aged 15-49 in the New York City area reveals that island-born Puerto Rican women living in New York rely on female sterilization to nearly the same extent as do women living in Puerto Rico (45% and 41%, respectively) and that mainland-born Puerto Rican women use sterilization as much as do all women in the United States (19% for both groups). Puerto Rican women in New York use reversible methods to a greater extent than do women in Puerto Rico (22% v. 16%), but to a lesser extent than do all women in the United States (37%). Although mainland-born Puerto Rican women in New York use reversible methods more than do island-born women in New York (42% v. 23%), they tend not to adopt these methods to the same extent as do all U.S. women during the early reproductive years, when education and employment are critical to socioeconomic attainment. PMID- 1426186 TI - The new pills: awaiting the next generation of oral contraceptives. PMID- 1426187 TI - Adoption trends--up or down? PMID- 1426188 TI - Making distinctions. PMID- 1426189 TI - Manual of food quality control. 4. Rev. 1. Microbiological analysis. Food and Drug Administration. PMID- 1426190 TI - Consistency of sternal percussion performed manually and with mechanical thumper. AB - Auscultatory percussion is a technique that is potentially useful to study the acoustic behaviour of the chest. However, finger percussion, as used in this technique, has not been previously assessed for consistency. We calculated the intrasubject variability and short-term reproducibility of this technique in 10 healthy subjects. We examined several indices of the output sound of two series of sternal percussion manoeuvres performed one hour apart by the same examiner. The results were compared to those obtained during sternal percussion performed by a mechanical thumper. Consistency for both finger and thumper percussion varied from 4.8-20.6 (coefficients of variation) for various acoustic indices. For thumper percussion, the average results were not significantly different from those of finger percussion. We conclude that finger percussion of the sternum is sufficiently consistent to be used as a tool to investigate the acoustic behaviour of the chest. PMID- 1426191 TI - Passive partitioning of respiratory volumes and time constants in ventilated patients. AB - If the thoracoabdominal partitioning of volumes in the mechanical respiratory apparatus was constant, one transducer of indirect spirometry should be sufficient to measure volume variations. To verify this hypothesis we used respiratory inductive plethysmography (RIP) in 16 paralysed patients, of whom eight had normal lungs and 8 had not, to measure: 1) the thoracoabdominal partitioning of volumes (400-1,200 ml) insufflated from either a syringe (Syr) or a ventilator (Vent); and 2) thoracic (Tho) and abdominal (Abd) time constants (T0.368) on spontaneous deflation to barometric pressure. In eleven additional subjects with normal lungs we measured only the time constants. 1) Correlation coefficients of the calibration lines were in all but one subject > 0.98. In all patients the error of volume was < +/- 10% when either one of two coils alone was used to assess volumes with no difference between the two coils; 2) Partitioning varied little with volumes (4 +/- 2%), but widely between subjects, with no group average significant difference between Syr and Vent; 3) T0.368 were identical for Tho and Abd except in one patient; 4) Partitioning and T0.368 were volume size independent. We conclude that, to measure volume variations and time constants in ventilated, paralysed patients, the use of either a thoracic or abdominal single coil RIP is justified. We also provide the normal range for time constant in 19 subjects (0.73 +/- 0.29 s). PMID- 1426192 TI - Toxoplasma pneumonitis: fatal presentation of disseminated toxoplasmosis in a patient with AIDS. AB - Toxoplasma gondii infection is an uncommon cause of pneumonitis in patients with acquired immune deficiency syndrome (AIDS). We report a case of fatal pulmonary toxoplasmosis, which clinically resembled Pneumocystis carinii pneumonia (PCP). Conventional diagnostic methods for toxoplasmosis lack sensitivity. Bronchoscopy and histological evaluation of transbronchial biopsy specimens failed to identify the infecting organism. At autopsy there was evidence of disseminated infection. PMID- 1426193 TI - Upper lobe infiltrate with cough, fever, fatigue. PMID- 1426194 TI - Views and news from Melbourne, the Sixth World Conference on Lung Cancer. The EORTC Lung Cancer Co-operative Group. PMID- 1426195 TI - Bronchial hyperresponsiveness, genetic predisposition and environmental factors: the importance of epidemiological research. PMID- 1426196 TI - Long-term inhaled corticosteroid therapy in chronic airways obstruction. PMID- 1426197 TI - Does airway smooth muscle care about platelet-activating factor? PMID- 1426198 TI - How to express the reversibility of bronchial obstruction? PMID- 1426199 TI - Factors associated with bronchial hyperresponsiveness in Australian adults and children. AB - To accurately assess putative risk factors for bronchial hyperresponsiveness (BHR), we have used multivariate models to analyse data from 4,366 children living in four regions and from 878 adults. A standard protocol was used to measure bronchial responsiveness to histamine. The prevalence of BHR was high at 7-9 yrs (16-18%), decreased significantly at 11-14 yrs (7-8%), and then increased in adults (12-14%). Atopy was the most important risk factor for BHR at all ages. In children, parental asthma, early respiratory illness and being born in Australia also had a significant influence, and eating fish more than once a week had a protective effect. No effect of parental smoking, gender or race was found. In adults, BHR was associated with being female and with smoking history. It appears that many factors have a significant influence on the presence of BHR, with environmental factors, particularly atopy, birthplace and diet, being the most important. PMID- 1426200 TI - Reproducibility of childhood respiratory symptom questions. AB - The reproducibility of answers to childhood respiratory symptom questions was investigated by administering two childhood respiratory symptom questionnaires twice, with a one month interval, to the same population of Dutch school children. The questionnaires were completed by the parents of 410 children from 6 12 yrs old. One questionnaire was developed by the World Health Organization (WHO). The other questionnaire was developed for use by school health services and was based mainly on the American Thoracic Society (ATS) questionnaire for respiratory symptoms in childhood. It was called the Child Health Care (CHC) Questionnaire. Half of the parents received a questionnaire in which the WHO questions came first on both occasions, the other half a questionnaire in which the CHC questionnaire came first on both occasions. The reproducibility of the answers was assessed by calculating Cohen's Kappa, a chance-corrected measure of association. Questions about "wheeze", "asthma", "bronchitis", "cough and phlegm", and "pneumonia" were found to give good to excellent reproducibility, with Kappa values ranging from 0.60-0.96. Questions about "phlegm", "cough", "chest congestion" and "runny/congested nose" were less satisfactory in this respect, with Kappa values generally well below 0.60. The reproducibility of the answers did not depend on the order in which the questionnaires were administered, on the gender or age of the child, or on the smoking habits or educational level of the parents. PMID- 1426201 TI - Influence of short-term passive smoking on symptoms, lung mechanics and airway responsiveness in asthmatic subjects and healthy controls. AB - We studied the acute effect of passive smoking on symptoms, lung mechanics and airway responsiveness. Twenty four patients with mild to moderate bronchial asthma (11 male and 13 female; mean(SD) age 34(15) yrs; forced expiratory volume in one second (FEV1) 91(17) % pred) were investigated. Sixteen of them had a history of passive smoke-induced respiratory symptoms. For comparison we studied 16 controls (7 male and 9 female; mean(SD) age 31(9) yrs; FEV1 106(13) % pred). On two different days, the subjects were exposed in an exposure chamber for one hour to either ambient air (Sham) or environmental tobacco smoke (ETS). During exposure to ETS, the mean concentrations of particles and CO were 3,095 micrograms.m-3 and 20.3 ppm, respectively. Before and immediately after exposure, symptoms and lung mechanics were assessed, followed by an inhalation challenge to determine the provocative concentrations of methacholine necessary to increase specific airway resistance (sRaw) by 100%, (PC100sRaw), and to decrease FEV1 by 20% (PC20FEV1). In the asthmatic subjects, during Sham exposure, mean (SEM) decrease of sRaw and FEV1 was 0.23(0.22) cmH2O.s and 0.04(0.03) l, respectively, (NS). During ETS, mean(SEM) decrease of sRaw and FEV1 was 0.55(0.46) cmH2O.s and 0.13(0.06) l, respectively. The significance of this decrease, however, disappeared when taking into account the individual variability of FEV1. Geometric mean(SEM) PC100sRaw and PC20FEV1 were 0.35(1.32) and 0.23(1.34) mg.ml-1 after Sham, and 0.34(1.37) and 0.28(1.36) mg.ml-1 after ETS, respectively, with no difference between the two study days. In the controls, the two exposure conditions did not exert any significant effects on sRaw, FEV1 and airway responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426202 TI - Inhaled beclomethasone improves the course of asthma and COPD. AB - The effects of inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, on the long-term course of asthma and chronic obstructive pulmonary disease (COPD) were investigated in a prospective, controlled study, over three years. During the first two years, patients were treated with a bronchodilator only (salbutamol or ipratropium bromide). Fifty six patients (28 asthma, 28 COPD), with an unfavourable course of disease during bronchodilator therapy alone (an annual decline in forced expiratory volume in one second (FEV1) of > or = 80 ml.yr-1 in combination with at least one exacerbation.yr-1), were selected for additional treatment with inhaled beclomethasone dipropionate (BDP), 800 micrograms daily, during the third year. The FEV1 and provoking concentration of histamine producing a 20% fall in FEV1 (PC20-histamine) were assessed at six monthly intervals. In asthma, the annual decline in prebronchodilator FEV1 of 158 ml.yr-1 during bronchodilator therapy alone was followed by a significant increase of 562 ml.yr-1 during months 1-6 of BDP treatment (p < 0.0005). During months 7-12 of BDP, the FEV1 declined slightly with -31 ml.yr-1, which was not statistically different from the annual decline before steroid therapy (p = 0.17). In COPD, the increase of 323 ml.yr-1 during months 1-6 of treatment with BDP was different from the annual decline of -156 ml.yr-1 before BDP (p < 0.05). The PC20-histamine improved by 308 doubling doses during 1-12 months of BDP in asthma (p < 0.05) but not in COPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426203 TI - Inhaled steroids modify bronchial responses to hyperosmolar saline. AB - We investigated the effects of inhaled beclomethasone dipropionate (BDP) on airway sensitivity (provocative dose producing a 20% fall in forced expiratory volume in one second (FEV1) from baseline (PD20)) and reactivity (slope of the dose-response curve) to inhaled aerosols of hyperosmolar (4.5%) saline, and histamine or methacholine. This was an open study on 13 patients referred to the laboratory by their respiratory physician for investigation of their asthma. These challenges were performed on separate days before (initial visit) and 8.8 +/- 0.8 (SD) weeks (range 5.6-12.4 weeks) after (visit 1) a treatment period with BDP (dose range 600-1,500 micrograms.day-1). At visit 1 there was a significant reduction in sensitivity to 4.5% NaCl and histamine/methacholine and in reactivity. The PD20 increased 5.6 fold for 4.5% NaCl and 4.1 fold for histamine/methacholine. All patients remained responsive to histamine/methacholine and a fall in FEV1 > 20% to 4.5% saline was documented in 10 of the 13 patients. We conclude that treatment with BDP reduces sensitivity and reactivity to both osmotic and pharmacological challenge. PMID- 1426204 TI - The effects of indomethacin on the refractory period to hypertonic saline-induced bronchoconstriction. AB - The purpose of this study was to determine the effect of pretreatment with indomethacin on the refractory period to hypertonic saline-induced bronchoconstriction. In a double-blind, placebo-controlled, randomized trial nine asthmatic subjects underwent two hypertonic saline challenges, 60 min apart, on a control day and after premedication with indomethacin 50 mg or matching placebo, twice daily for three days. Premedication with indomethacin did not change airway responsiveness to the initial hypertonic saline challenge. The mean maximal % fall in specific airway conductance (sGaw) was 40.3, 44.1 and 47.6% on the control, placebo and indomethacin days, respectively. Subjects were significantly less responsive to the second hypertonic challenge as compared to the initial challenge on all three study days. There was a variable effect of indomethacin pretreatment on the refractory period. Five subjects lost their refractory period after indomethacin, when the variability of the test was taken into account. This suggests that there may be contributory mechanisms to the refractory period other than the release of protective prostanoid metabolites. PMID- 1426205 TI - Platelet-activating factor-induced contraction of human isolated bronchus. AB - In recent years, platelet-activating factor (PAF) has been strongly implicated as a mediator involved in asthma. In non-asthmatic subjects, aerosolized PAF has been shown to cause bronchoconstriction. The mechanism of this in vivo effect is unknown. We have previously shown that PAF causes a contraction of human isolated bronchus that varies in magnitude between patients, and within tissues from the same patient. To examine the possibility that this variability in contraction was secondary to PAF-induced release of mediators from inflammatory or epithelial cells within the tissue, we examined the relationship between contractile responses to PAF and the presence of inflammatory or epithelial cells. We studied eight tissues from five patients. Of the eight tissues, four contracted, whilst four failed to contract, to PAF (7 x 10(-7) M). After the contractile response to PAF had been assessed by observing changes in isometric tone in vitro, bronchial rings were examined histologically to enable the quantification of inflammatory cell numbers and intact epithelium. No significant correlation was observed between the magnitude of contractions and numbers of eosinophils, neutrophils, lymphocytes, plasma cells, total cells or percentage intact epithelium. We conclude that it is unlikely that the variability in response to PAF in human isolated airways is related to the variability in inflammatory cell numbers or to the presence of epithelium. Thus, the contraction induced by PAF is probably not mediated via the release of a secondary mediator from the particular cells examined in this study. PMID- 1426206 TI - A comparison of six different ways of expressing the bronchodilating response in asthma and COPD; reproducibility and dependence of prebronchodilator FEV1. AB - Various indices are used to express the bronchodilating response. It is unclear, however, which index is most informative. The aim of this study was to compare six expressions of the bronchodilating response and to examine: 1) the independence of the prebronchodilator forced expiratory volume in one second (FEV1); and 2) the reproducibility of the bronchodilating response. Bronchodilating responses (increases in FEV1 60 min after salbutamol 400 micrograms and ipratropium bromide 80 micrograms) on six test occasions, during two years, of 183 patients (72 asthma, 111 chronic obstructive pulmonary disease (COPD)) from a large bronchodilator intervention study were used. The dependence of the prebronchodilator FEV1 was investigated both between patients (cross sectional analysis) and within patients (longitudinal analysis) by means of linear regression analysis. The reproducibility of the bronchodilating response was calculated by means of the coefficients of variation (CVs) of the six bronchodilating responses during two years. The CVs of the six expression indices were compared by analysis of variance (ANOVA). No index was independent of the prebronchodilator FEV1. However, some indices were significantly more dependent on the prebronchodilator lung function and, therefore, less reproducible than others. The "% initial" index (change as a percentage of the prebronchodilator value) was the most dependent on the prebronchodilator lung function and had the worst reproducibility (CV ranged from 50-61%). The "% possible" (change as a percentage of the predicted minus prebronchodilator value) and "% achievable" (change as a percentage of the maximal postbronchodilator minus prebronchodilator value) indices were the least dependent on the prebronchodilator value and had the highest reproducibility (CV ranging from 34-53%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426207 TI - Bronchodilatory effect of inhaled zardaverine, a phosphodiesterase III and IV inhibitor, in patients with asthma. AB - Zardaverine is a newly developed selective phosphodiesterase III and IV inhibitor. This study investigates the bronchodilatory properties of zardaverine, administered by inhalation. Twelve patients with reversible bronchial obstruction (increase in forced expiratory volume in one second (change FEV1 % predicted) at least 15% after 200 micrograms salbutamol, median age 31 yrs, range 21-54 years) entered the double-blind, crossover study. Four puffs of either zardaverine (total dose 6 mg) or placebo were inhaled at 15 min intervals. Pulmonary function (specific airway conductance (sGaw) and FEV1 was measured by body plethysmography at regular intervals (5 and 12 min after each puff and, in addition, 30, 60, 120, 180 and 240 min after the last puff). Compared to placebo, sGaw and FEV1 increased significantly during the first hour of repeated inhalations, but not during the entire observation period of almost 5 h. The maximum mean difference between zardaverine and placebo for FEV1 was 0.3 l or 12% and occurred approximately 1 h after inhalation of the first puff. In seven patients FEV1 increased by > 15%. The duration of action varied considerably between patients. Three patients complained of side-effects (headache, drowsiness, vertigo, nausea), and one of these dropped out of the study due to vomiting. We conclude that inhalational administration of zardaverine has a modest and short-lasting bronchodilating activity. PMID- 1426208 TI - Lipopolysaccharide (LPS) inhalation in healthy subjects increases neutrophils, lymphocytes and fibronectin levels in bronchoalveolar lavage fluid. AB - Bacterial endotoxin has been suggested as responsible for the development of subjective symptoms and transient or chronic lung function impairment seen after exposure to organic dusts in cotton mills, poultry houses, swine confinement buildings and saw mills. Animal experiments have demonstrated bronchoalveolar neutrophilia being the most prominent cell response in animals following bacterial lipopolysaccharide (LPS) inhalation. The present study was conducted to obtain information on some aspects of the early inflammatory response to inhaled LPS in man. Eight healthy nonsmoking subjects, 23-27 yrs old, underwent bronchoalveolar lavage (BAL), 3 h after a provocation test with 100 micrograms LPS from E. coli dissolved in 2 ml isotonic NaCl. The solution was aerosolized with a jet nebulizer and inhaled. The calculated dose delivered to the lung was approximately 25 micrograms, which equals exposure in some occupational settings. The BAL data for each individual subject were compared with data from a control BAL performed at least 6 weeks prior to the LPS challenge. The major cellular response to LPS, reflected in BAL fluid, was an approximately hundredfold increase in neutrophils. The total number of lymphocytes was on average tripled. The alveolar macrophage phagocytosis of opsonized yeast particles in vitro was significantly reduced. A further indicator of an ongoing inflammation was an increase in fibronectin. No changes were seen in the levels of BAL albumin, indicating that the elevated level of fibronectin could not be explained by an increased permeability, but rather by a local production. The results correspond with data from animal studies and further supports the hypothesis that bacterial LPS is important in the pulmonary reaction induced by organic dusts. PMID- 1426210 TI - Breathlessness perception in airways obstruction. PMID- 1426209 TI - Steroid-induced myopathy and its significance to respiratory disease: a known disease rediscovered. AB - Skeletal muscle myopathy is a well-known side-effect of systemically administered corticosteroids. In recent years renewed attention is being paid to the involvement of the respiratory muscles and its consequent significance in pulmonary patients. Two different clinical patterns of steroid-induced muscular changes are known. In acute myopathy and atrophy after short term treatment with high doses of steroids, generalized muscle atrophy and rhabdomyolysis occur, including the respiratory muscles. Chronic steroid myopathy, occurring after prolonged treatment with moderate doses, is characterized by the gradual onset of proximal limb muscle weakness and may be accompanied by reduced respiratory muscle force. Animal studies demonstrated diaphragmatic myopathy and atrophy similar to the alterations in peripheral skeletal muscles. Fluorinated steroids induced selective type IIb (fast-twitch glycolytic) fibre atrophy, resulting in changes in contractile properties of the diaphragm. Non-fluorinated steroids may also induce histological, biochemical and functional alterations in the diaphragm. Observations in patients with collagen vascular disorders and with asthma and chronic obstructive pulmonary disease (COPD) underline the potential hazards of treatment with corticosteroids to respiratory muscle structure and function. PMID- 1426211 TI - Is long-term treatment with inhaled steroids in adults hazardous? PMID- 1426212 TI - Experimental exposures to nitrogen dioxide. PMID- 1426213 TI - Perceived effect on shortness of breath of an acute inhalation of saline or terbutaline: variability and sensitivity of a visual analogue scale in patients with asthma or COPD. AB - The purpose of the study was to validate a bipolar visual analogue scale (VAS) to assess the perceived effect on shortness of breath of an acute inhalation and to search for differences in perception between asthmatics and subjects with chronic obstructive pulmonary disease (COPD). Thirty two subjects with airway obstruction and a diagnosis of either asthma (n = 16) or COPD (n = 16) received three consecutive inhalations of isotonic saline, followed by two inhalations of 400 micrograms terbutaline. Saline was perceived by asthmatics as a slight improvement: VAS (median, 95% confidence interval) 9%, 0-18% of line length. COPD subjects could be separated into two subgroups: "high perceivers" (n = 8, VAS 43%, 33-53%) and "low perceivers" (n = 8, VAS 5%, 3-7%). The median intrasubject coefficient of variation of the three post-saline VAS ratings was 19.4% (asthma), 12.5% (COPD high perceivers), and 14.5% (COPD low perceivers). After terbutaline, asthmatics had, by selection, a larger increase in forced expiratory volume in one second (FEV1) than COPD subjects. However, for other indices (expiratory specific resistance, inspiratory vital capacity and maximal inspiratory flow at 50% forced vital capacity) the changes were smaller in COPD low perceivers than in both asthmatics and COPD high perceivers. The parallel improvement in VAS was 24%, 20-39% (asthma), 15%, 6-25% (COPD high perceivers) and 1%, -1-8% (COPD low perceivers). The most sensitive index was FEV1 in asthmatics, vital capacity in COPD subjects, VAS being among the most sensitive indices in the former, but among the least sensitive in the latter. We conclude that the sensitivity of this VAS to bronchodilation is better in asthmatics than in COPD subjects. The latter can however be separated into subgroups with high and low level of perception. PMID- 1426214 TI - Sequential treatment with low dose almitrine bismesylate in hypoxaemic chronic obstructive airways disease. AB - Daily dose schedules of 100-200 mg of almitrine bismesylate improve arterial blood gases in patients with hypoxaemic chronic obstructive airways disease (COPD) but dose related side effects are evident. In the present study, daily doses approximately half of those previously used were employed in a randomised double blind manner in 85 patients (age 35-79 years) with hypoxaemic COPD. After a one month period to check stability of arterial blood gases, patients were allocated to almitrine (A) or placebo (P) using an unequal code (60% A, 40% P). Tablets, 50-100 mg daily were stopped for one month after 3, 6 and 9 months to counteract drug accumulation. 50 patients in group A and 35 in group P were comparable on entry; mean age 65 (SD = 8) yrs., Pao2 7.8 (0.7) kPa (58.3 (5.0) mmHg), PaCO2 5.8 (0.8) kPa (43.2 (6.0) mmHg), forced expiratory volume in one second--FEV1 0.89 (0.25) l and 6 minute walking distance 296 (97) metres. The improvement in baseline PaO2 values was the same 0.8-1.3 kPa (6-9.8 mmHg) as with previous higher dose therapy. Approximately one third of patients did not respond, defined as PaO2 elevation > 0.67 kPa (5 mmHg). The sequential dosing scheme stabilised blood levels of almitrine within the therapeutic range of 280 300 ng.ml-1. After withdrawal of therapy arterial blood gases and spirometry reverted to pre-treatment levels, suggesting no permanent reversal of pathophysiology. Dose related side effects of breathlessness, indigestion and peripheral neuropathy were not observed. Nerve conduction studies revealed no difference in peripheral nerve dysfunction in hypoxaemic COPD between active and placebo therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426215 TI - A twelve month comparison of salmeterol with salbutamol in asthmatic patients. European Study Group. AB - The efficacy and tolerability of salmeterol, 50 micrograms b.i.d. was compared for three months with salbutamol, 200 micrograms q.i.d., administered from metered-dose inhaler. For the following nine months, safety and clinic lung function was monitored on salmeterol, 50 micrograms b.i.d., compared with salbutamol, 200 micrograms b.i.d. This comparison was made in a multicentre, double-blind, parallel-group study of 667 moderate asthmatics, who had a forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR) > 50% predicted, a 15% reversibility to inhaled salbutamol and who were experiencing symptoms. Throughout the first three month treatment period, both morning and evening PEFR were significantly higher on treatment with salmeterol than salbutamol (mean differences between the treatments 30 l.min-1 for morning, p < 0.001, and 11 l.min-1 for evening, p < 0.01). In addition, the diurnal variation in PEFR, nocturnal and daytime symptoms and use of additional salbutamol were significantly lower in the salmeterol treated group. This improvement was also apparent in the separate subpopulations of patients taking no concurrent glucocorticosteroid or concurrent inhaled and/or oral glucocorticosteroids. Both treatments were well-tolerated throughout the 12 months of treatment. There was a lower incidence of asthma and related events during salmeterol treatment compared to salbutamol treatment subgroups. The results of the study clearly demonstrate that salmeterol, 50 micrograms b.i.d., is well-tolerated and more effective than salbutamol, 200 micrograms q.i.d., in the treatment of moderate asthma. PMID- 1426216 TI - Easy bruising as a side-effect of inhaled corticosteroids. AB - We wished to determine the prevalence of easy bruising in patients taking inhaled corticosteroids (ICS) compared with those who do not. Differences in age, dosage and duration of use of ICS between patients who bruised and those who did not were also investigated. Confidential questionnaire surveys were conducted over a 6 month study period amongst patients attending a respiratory out-patient clinic and taking regular ICS, and a control group of patients attending non-respiratory clinics and not taking any form of corticosteroids. Patients with bleeding disorders or taking oral steroids, non-steroidal anti-inflammatory drugs or anticoagulants were excluded from the study. Questionnaires from 202 respiratory patients using ICS (group A) were compared with 204 non-ICS patients (Group B) of similar age and sex distribution. Significantly more patients in Group A reported easy bruising than in group B (47 vs 22%, relative risk 2.18, 95% confidence interval (95% CI) 1.62-2.94), and it was the commonest reported symptom. In Group A, the patients that reported easy bruising tended to be older (61 vs 52 yrs), on higher daily dosages (1,388 vs 1,067 micrograms) and had been taking inhaled corticosteroids for longer (55 vs 43 months) than non-bruisers. Overall, females reported easy bruising more frequently than males in both groups. However, comparing Group A with Group B, males taking ICS had a higher relative risk for bruising than females (males, relative risk 5.80, 95% CI 2.38-14.13; females, relative risk 1.80, 95% CI 1.32-2.44).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426217 TI - Bronchial vagal tone and responsiveness to histamine, exercise and bronchodilators in adult patients with cystic fibrosis. AB - Atopy and bronchial responsiveness to histamine, exercise and bronchodilators were investigated in 18 adult patients with cystic fibrosis (CF). Reversibility of airflow limitation was measured after ipratropium bromide and terbutaline, and histamine and exercise provocation tests were performed. Histamine hyperresponsiveness was observed in 10 out of 18 patients and was not confined to those with severe airway obstruction. The positive histamine responders showed significantly better bronchodilatation after terbutaline, when compared to negative histamine responders. Histamine responsiveness was not related to atopy or exercise responsiveness. Exercise challenge caused bronchodilatation without bronchoconstriction in all patients. The exercise-induced bronchodilatation correlated with bronchodilatation after ipratropium bromide. It is proposed that an increased vagal tone may lead to an increased resting bronchomotor tone which can be reduced by ipratropium bromide and by exercise in adult patients with cystic fibrosis. PMID- 1426218 TI - Comparison of nebulized and intravenous terbutaline during exacerbations of pulmonary infection in patients with cystic fibrosis. AB - Twenty three patients completed a double-blind study, comparing intravenous and nebulized terbutaline, during the first four days of a pulmonary exacerbation of cystic fibrosis (CF), with follow-up to day 10. Routine treatment with chest physiotherapy and appropriate intravenous antibiotics was given to all patients. The best peak flow rate (PF), forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), in the past year and at entry to the study, revealed no significant difference between the groups. However, on day 10, PF, FEV1 and FVC, of the nebulizer group remained significantly reduced compared to best values in the previous year, whereas the PF and FEV1 in the intravenous group were not significantly reduced compared to the best values in the previous year. Comparison of regression lines showing the overall rate of improvement of PF, FEV1 and FVC between the two groups showed that the rate of improvement of each parameter was more rapid in the group receiving intravenous terbutaline. This was statistically significant for PF. It is possible that during acute exacerbations of infection, sputum retention makes it more difficult for the inhaled bronchodilators to reach the airways and intravenous therapy is, therefore, more beneficial. PMID- 1426219 TI - Effects of repeated exposure to 4 ppm nitrogen dioxide on bronchoalveolar lymphocyte subsets and macrophages in healthy men. AB - Following the basal descriptive studies of the bronchoalveolar inflammatory cell response induced by single exposure with nitrogen dioxide (NO2) in man, it was considered important to clarify the cell response to repeated exposure with NO2. This investigation was, therefore, undertaken with bronchoalveolar lavage (BAL) 3 weeks before and 24 h after six repeated exposures with 4 ppm NO2 (7 mg.m-3) in ten healthy volunteers. The exposures were performed during 20 min and every second day. Analysis of the recovered BAL fluid demonstrated that repeated exposures to NO2 caused a lung cell response different from that reported after a single exposure. Amounts of lavaged alveolar macrophages, B-cells, and natural killer (NK)-cells were decreased and the T-helper-inducer/cytotoxic-suppressor cell ratio was altered, but there was no lymphocytosis or mastocytosis as after single exposure. Lymphocyte numbers in peripheral blood were reduced after exposure. These results suggest that repeated exposure with NO2 adversely affects the immune defence. This could contribute to the increased susceptibility to airway infections reported to be associated with NO2 exposure. PMID- 1426220 TI - Thymomodulin increases release of granulocyte-macrophage colony stimulating factor and of tumour necrosis factor in vitro. AB - To evaluate the effects of thymomodulin (TMD), a thymic biological response modifier derived from calf thymus, on the release of various cytokines involved in the lung immune reactions, human alveolar macrophages (AM) and peripheral blood lymphocytes (PBL) were cultured either alone or in co-cultures. In co cultures of AM with PBL, TMD did not induce any change in gamma-interferon (gamma IFN) and interleukin-1 (IL-1) secretion, while it was able to increase the level, of tumour necrosis factor (TNF) (TMD 100 micrograms.m-1, p < 0.05 vs control cultures), and of granulocyte macrophage colony-stimulating factor (GM-CSF) (TMD 1, 10 and 100 micrograms.ml-1 p < 0.05, < 0.05 and < 0.01, respectively, vs control cultures). In cultures of AM alone, TMD did not induce changes in the levels of any of the tested cytokines, whilst in supernatants from PBL lymphocyte cultures, TMD at 1, 10 and 100 micrograms.ml-1 increased the amounts of GM-CSF (p < 0.01 each comparison vs control cultures). Thus, TMD seems to directly stimulate lymphocytes to secrete GM-CSF and to modulate macrophage-lymphocyte interactions, resulting in the release of TNF and GM-CSF. PMID- 1426221 TI - Relationship of upper airways disorders to FEV1 and bronchial hyperresponsiveness in an epidemiological study. AB - Associations of upper airways disorders (UAD) with forced expiratory volume in one second (FEV1) and bronchial methacholine response were studied, taking smoking habits into account. We used epidemiological data drawn from a population of 324 men, aged 27-58 yrs. Lower FEV1 level was related to hay fever (p = 0.01), usual (p = 0.01) and chronic (p = 0.02) rhinitis and common cold on the day of examination (p = 0.04). Allowance for the major potential confounding factor, tobacco smoking, showed similar results. Bronchial methacholine response was heightened in men reporting hay fever compared to those without (p = 0.01) but also in men reporting chronic rhinitis (p = 0.06), a group which did not exhibit skin prick test positivity more often than other subjects. Exclusion of asthmatics and taking into account smoking and skin prick test positivity yielded mostly similar results. Our data support the hypothesis of an association between lung impairment, as assessed by lower FEV1 and bronchial hyperresponsiveness to methacholine, and different types of UAD, allergic or not. PMID- 1426222 TI - Relationship of the type of tobacco and inhalation pattern to pulmonary and total mortality. AB - Data from The Copenhagen City Heart Study, a prospective population study, were analysed to investigate the influence of the type of tobacco and inhalation on pulmonary and total mortality. The study sample comprised 6,511 men and 7,703 women, selected randomly after age-stratification from the general population. There were 2,986 plain cigarette smokers, 3,222 filter cigarette smokers, 1,578 smokers of cheroots/cigars, 433 male pipe smokers and 773 subjects smoking more than one type of tobacco. From 1976 until the end of 1989, 2,765 subjects died. Lung cancer was considered as main death cause in 268. Chronic obstructive pulmonary disease (COPD) was considered as the main cause in 94 cases and main or contributory cause of death in 195 cases (COPD related mortality). Current smokers had a higher risk of total mortality compared to lifetime nonsmokers: the relative risks (RR) ranged between 1.2 for male pipe smokers and 2.4 for female plain cigarette smokers. With regard to lung cancer mortality, the RR ranged between 4.1 for male pipe smokers and 7.9 for female plain cigarette smokers. Even higher RR values were estimated for COPD related mortality. In both sexes, the RR for the investigated end-points were lower in cheroot/cigar smokers and in pipe smokers than in cigarette smokers, but these differences were markedly diminished after an adjustment for the inhalation habit. The present study substantiates the view that tobacco smoking increases pulmonary and total mortality. The small differences between the various types of tobacco are probably caused by different inhalation patterns. PMID- 1426223 TI - Influence of posture on mechanical parameters derived from respiratory impedance. AB - The influence of posture on respiratory mechanics was investigated in 10 healthy volunteers, using the forced pseudorandom noise technique. Subjects were studied in four randomly selected positions: sitting; sitting with the head turned sideways; supine; and prone with the head turned sideways. Respiratory compliance (Crs), inertance (Irs) and resistance estimated at 4 Hz (R4), were calculated by fitting respiratory impedance by a 4 parameter model with a frequency dependent resistance. When subjects changed from sitting to lying, whilst maintaining the head in the same position in relation to the body, Irs increased and Crs decreased, probably due to gravitational effects. R4 was significantly higher in the supine position than in either of the sitting or the prone positions. These results demonstrate that changes in lung volume cannot completely explain the influence of posture on respiratory resistance, and indicate upper airway geometry as a determinant factor of respiratory resistance. PMID- 1426224 TI - Comparison of nebulized and sprayed topical anaesthesia for fibreoptic bronchoscopy. AB - We compared the efficacy of nebulized (N) and sprayed (S) topical anaesthesia prior to fibreoptic bronchoscopy in a blinded study involving 54 patients aged 57 +/- 26 yrs (mean +/- SD). Cough frequency, recorded on cassette tape, was the index of efficacy. All patients received 100 mg lignocaine sprayed into the pharynx, or nebulized in random order prior to bronchoscopy, and all received intravenous diazepam sedation. Each patient received a further 100 mg of lignocaine solution through the bronchoscope onto the vocal cords and major airways during the procedure. No significant difference was found in overall cough frequency between N and S groups (8.7 +/- 6.9 coughs.min-1 N vs 10.5 +/- 6.0 S), and cough frequency was also similar between N and S during the periods above and below the vocal cords. Furthermore, no differences were found in cough frequency between N and S among smokers, patients with asthma and COPD, and patients who had a biopsy procedure, although a trend was seen in all comparisons towards a lower cough frequency with the nebulized route. Most patients in the S group found the spray unpleasant, whereas only one in the N group complained. We conclude that nebulized and sprayed lignocaine have similar efficacy as topical anaesthetics in fibreoptic bronchoscopy, but patient preference favours the nebulized route. PMID- 1426225 TI - The accuracy of dry gas meters at continuous and sinusoidal flows. AB - Dry gas meters are used in physiology laboratories to measure minute ventilation. The accuracy of these meters must be known since an error, of for instance 5%, affects the subsequent calculations for oxygen consumption by the same amount. Two precalibrated DTM-325 dry gas meters (American Meter Co., Philadelphia, PA, USA) were therefore tested for accuracy against a 350 l Collins chain-compensated gasometer. Provided that at least 25 l was passed per measurement then: a. continuous flows (air saturated with water vapour) between 60 and 150 l.min-1 were measured with an error of < 1%; and b. sinusoidal flows (ambient air) between 8 and 100 l.min-1 were misread by < 1% and the error was still within 2% at 140 l.min-1. It may, therefore, be concluded that the two precalibrated dry gas meters studied are valid volume measuring devices. PMID- 1426226 TI - Massive pleural effusion: an unusual presentation of Castleman's disease. AB - Giant lymph node hyperplasia (Castleman's Disease) is a rare cause of pleural effusion. We report the case of a 51 yr old West Indian male, who presented with a recurrent massive pleural effusion, due to a tumour arising from the pleura. He underwent parietal pleurectomy and subtotal excision of the tumour. Histological analysis of the specimen showed the features of multicentric Castleman's disease. Nine months following surgery he remains well, with no recurrence of the effusion. PMID- 1426227 TI - Chronic extrinsic allergic alveolitis in a family with idiopathic pulmonary fibrosis: the importance of histological diagnosis. AB - We report a patient who presented with progressive exertional dyspnoea, chronic cough and radiographic signs of interstitial lung disease. Since several of his family members were known to have familial idiopathic pulmonary fibrosis he was also suspected to suffer from this disease. After thorough investigation, including histological examination of lung biopsies obtained by thoracoscopy, a diagnosis of chronic extrinsic allergic alveolitis was made. Current knowledge of familial idiopathic pulmonary fibrosis is discussed. This case report underlines the importance of a histological diagnosis in interstitial lung disease. PMID- 1426228 TI - Vomiting in a patient with an Angelchik prosthesis. PMID- 1426229 TI - Risk of lung cancer and mesothelioma after cessation of asbestos exposure. PMID- 1426230 TI - Ring finger in the peroxisome assembly factor-1. AB - The peroxisome assembly factor-1 (PAF-1) is reported here to contain the signature subsequence for a ring finger motif in its carboxyl-terminus. This conserved subsequence in PAF-1 may be the key to a gene expression regulatory pathway important in peroxisome biogenesis. PMID- 1426231 TI - The 5' untranslated region of the human cellular glutathione peroxidase gene is indispensable for its expression in COS-7 cells. AB - We studied the expression of the human cellular glutathione peroxidase (GPx) gene, from which a key enzyme containing selenocysteine (Scy) at the active site is produced. Expression of some human GPx gene mutants in COS-7 cells revealed that the 5' untranslated region (utr) was necessary for expression of the GPx gene, since mutant genes having 10 base pairs (bps) at the 5'utr (the complete had 311 bps) expressed GPx at very low levels. The genes with 311 or 408 bps at the 5'utr were better expressed than those having 257 bps. The GPx gene having 133 bps at the 3'utr (80 bps shorter than the entire length) was highly expressed. This deletion did not influence expression. We constructed some mutants in which 3 bases were altered at the upstream region of the Scy UGA codon in the frame of the GPx gene, by site-directed mutagenesis. GPx expression decreased but the expression was restored. Therefore, the upstream region of the in-frame Scy codon was not essential in the Scy decoding mechanisms. Finally, the 5'utr was essential for the expression of GPx gene. However, the deletion of a part of the 3'utr and the site-directed mutation upstream of the Scy codon did not show drastic effects on the expression. PMID- 1426232 TI - Comparative analysis of sodium-dependent L-glutamate transport of synaptosomal and astroglial membrane vesicles from mouse cortex. AB - Uptake of [3H]L-glutamate into membrane vesicles prepared from either mouse cortical astrocyte cultures or synaptosomes was found to be an electrogenic sodium- and potassium-dependent transport process with saturable uptake kinetics. Pharmacological differences were revealed by using a variety of substrate analogues. L-trans-PDC inhibited the synaptosomal glutamate transport 2-4-fold stronger than the astroglial uptake. The substrate analogues DL-threo-beta hydroxy-aspartate, DL-aspartate-beta-hydroxamate, L-aspartate and D-aspartate inhibited glutamate transport of astroglial and neuronal membrane vesicles in a distinctive manner, whereas D-glutamate, quisqualate and dihydrokainate had no effect in either case. Immunoblotting and immunocytochemical labeling with antibodies against the rat brain glutamate transporter revealed the selective reaction of a band at about 75 kDa mol. wt. and a specific pattern of astrocyte immunostaining. PMID- 1426233 TI - Photoaffinity labeling of the phylloquinone-binding polypeptides by 2 azidoanthraquinone in photosystem I particles. AB - A photoaffinity label, 2-azido-9,10-anthraquinone, binds at the quinone-binding (Q phi) site with high affinity and can substitute for the secondary acceptor, phylloquinone, in photosystem I reaction center of spinach. Phylloquinone depleted photosystem I particles reconstituted with azido[3H]anthraquinone were illuminated with UV light and analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis. The large core polypeptides (psaA and/or psaB) were selectively labeled. The labeling was competitively inhibited in the presence of anthraquinone. These results indicate that the Q phi site is located on psaA or psaB polypeptides. PMID- 1426234 TI - The second cholera toxin, Zot, and its plasmid-encoded and phage-encoded homologues constitute a group of putative ATPases with an altered purine NTP binding motif. AB - It is shown that the second cholera toxin, Zot, ORF3 product of Pseudomonas plasmid pKB740, and ORF424 product of bacteriophage Pf1 are a group of closely related proteins containing a modified version of the purine NTP-binding motif, with a drastic substitution of tyrosine for a conserved glycine. They are distantly but reliably related to the product of gene I of filamentous bacteriophages which is a putative ATPase containing the classical NTP-binding motif and is involved in bacteriophage assembly and exit from the bacterial cell. Hydropathy analysis suggests that the Zot and gene I product may have a similar transmembrane topology. It is hypothesized that Zot may possess ATPase activity and modify the membrane structure of its target cells in an ATP-dependent fashion. Genes for Zot and the related protein of pKB740 are likely to have evolved from gene I of a Pf1-like bacteriophage. PMID- 1426235 TI - Human liver and human placenta both contain CMP-NeuAc:Gal beta 1-->4GlcNAc-R alpha 2-->3- as well as alpha 2-->6-sialyltransferase activity. AB - A high pH anion exchange chromatographic (HPAEC) system for the separation of isomeric sialo-oligosaccharide products was developed. Employing this system, using Gal beta 1-->4GlcNAc beta 1-->2Man alpha 1-->6Man beta 1-->4GlcNAc as a substrate, a Gal beta 1-->4GlcNAc-R alpha 2-->3-sialyltransferase activity was detected for the first time in human liver. This activity is expressed together with the prevalent alpha 2-->6-sialyltransferase. Furthermore, in addition to the major alpha 2-->3-sialyltransferase, a low but distinct activity of alpha 2-->6 sialyltransferase was detected in human placenta. This activity could not be found by methods based on methylation analysis or high resolution NMR spectroscopy. It is concluded that HPAEC, in combination with the use of the pentasaccharide as an acceptor substrate, is suited for the specific detection of minor, Gal beta 1-->4GlcNAc-specific sialyltransferase activities. PMID- 1426236 TI - Molecular cloning and developmental expression of a human kidney S adenosylmethionine synthetase. AB - cDNA clones encoding the human kidney S-adenosylmethionine synthetase (kidney type isozyme) were isolated. The amino acid sequence deduced from the cDNA indicates that this enzyme contains 395 amino acids and has a molecular mass of 43,660 Da. The predicted amino acid sequence of this protein shares 84% similarity with that of human liver S-adenosylmethionine synthetase (liver-type isozyme). In addition, the developmental expression of these two isozyme mRNAs has been studied in the human liver using the reverse transcription-polymerase chain reaction (RT-PCR). PMID- 1426237 TI - The thyroid hormone response element is required for activation of the growth hormone gene promoter by nicotinamide analogs. AB - N'-Methylnicotinamide and nicotinamide, which decreased in vitro ADP-ribosylation of nuclear proteins and/or cellular NAD+ content, selectively increased the basal expression of the rat growth hormone (GH) gene promoter and its response to triiodothyronine (T3). This increase was not found when the thyroid hormone response element (TRE) was deleted from the promoter. Transfection with an expression vector for the T3 receptor inhibited basal activity of the TRE containing promoter and repressed the stimulatory effect of N' methylnicotinamide. The addition of hormone relieved this inhibition and enhanced transcription above levels found in the absence of the transfected receptors. These results suggest a modulatory role of ADP-ribosylation in hormonal regulation of gene expression. PMID- 1426238 TI - Unexpected intron location in non-vertebrate globin genes. AB - The Caenorhabditis elegans and Artemia T4 globin sequences are highly homologous with other invertebrate globins. The intron/exon patterns of their genes display a single intron in the E and G helices respectively. Precoding introns in multirepeat globins are inserted in homologous positions. Comparison of the intron/exon patterns in the known globin gene sequences demonstrates that they are more diverse than first expected but nevertheless can be derived from an ancestral pattern having 3 introns and 4 exons. PMID- 1426239 TI - Families of metalloendopeptidases and their relationships. AB - Crystal structures available for four metalloendopeptidases have revealed zinc ligands for these enzymes. New sequence information has made it possible to compare the primary structures of the zinc-binding site in metalloendopeptidases. A scheme based on the zinc-binding site is proposed to classify metalloendopeptidases into five distinct families: thermolysin, astacin, serratia, matrixin, and snake venom metalloproteinases. Two histidines and one glutamate are zinc-ligands in the thermolysin family. Three histidines and one tyrosine are zinc ligands in the other four families, which are further distinguished by the identity of the residue following the third histidine and by the environment surrounding the tyrosine. PMID- 1426240 TI - Identification, characterization, and molecular cloning of a novel transporter like protein localized to the central nervous system. AB - During the course of large scale purification of the D1 dopamine receptor from rat brain, a protein of approximately 87,000 daltons (p87) was observed to copurify with the D1 receptor through four chromatographic steps. To characterize the nature of this protein, bovine and rat cDNA clones were isolated and sequenced. The bovine and rat clones were highly conserved (98.5% identity). Each clone possessed an open reading frame of 2226 base pairs encoding a protein of 742 amino acids (calculated MW of 82,500), containing three stretches of peptide sequence obtained from p87 sequence analysis. Comparison of the deduced peptide sequence of this protein with those found in available databanks revealed that it was a novel protein related to the family of nutrient transport proteins from eukaryotes and bacteria, including, the mammalian facilitated glucose transporters, the yeast transporters for maltose, lactose, and glucose, and the proton-driven bacterial transporters for arabinose, xylose, and citrate. In addition p87 also shares with these transporters a similar hydropathicity profile that suggests the presence of 12 transmembrane segments. The mRNA for p87 appears to be localized primarily, if not exclusively, to the central nervous system. Northern blot analysis reveals a message of approximately 4.8 kb in cortex, hippocampus, brain stem, and cerebellum, but no detectable signal in peripheral tissues such as spleen, liver, kidney, lung, heart, or skeletal muscle. Evidence form Western blot analysis and immunohistochemistry suggests that this protein may be expressed in intracellular organelles or the membrane of synaptosomes rather than plasma membrane. Based on its structure and properties, p87 appears to define a new class of transporter-like proteins. PMID- 1426241 TI - Three-dimensional structure of catalase from Micrococcus lysodeikticus at 1.5 A resolution. AB - The three-dimensional crystal structure of catalase from Micrococcus lysodeikticus has been solved by multiple isomorphous replacement and refined at 1.5 A resolution. The subunit of the tetrameric molecule of 222 symmetry consists of a single polypeptide chain of about 500 amino acid residues and one haem group. The crystals belong to space group P4(2)2(1)2 with unit cell parameters a = b = 106.7 A, c = 106.3 A, and there is one subunit of the tetramer per asymmetric unit. The amino acid sequence has been tentatively determined by computer graphics model building and comparison with the known three-dimensional structure of beef liver catalase and sequences of several other catalases. The atomic model has been refined by Hendrickson and Konnert's least-squares minimisation against 94,315 reflections between 8 A and 1.5 A. The final model consists of 3,977 non-hydrogen atoms of the protein and haem group, 426 water molecules and one sulphate ion. The secondary and tertiary structures of the bacterial catalase have been analyzed and a comparison with the structure of beef liver catalase has been made. PMID- 1426242 TI - Tandem translation of Bacillus subtilis initiation factor IF2 in E. coli. Over expression of infBB.su in E. coli and purification of alpha- and beta-forms of IF2B.su. AB - The protein synthesis initiation factor, IF2, in Bacillus subtilis has previously been characterized as being present in two forms, alpha and beta, of molecular mass 79 and 68 kDa, respectively, on the basis of their cross-reaction with anti E. coli IF2 antibodies and by the DNA sequence of the gene for IF2, infBB.su. In this work we have cloned infBB.su in E. coli cells. Two proteins of molecular mass identical to the B. subtilis IF2 alpha and -beta were over-expressed and purified using a new three-step ion-exchange chromatography procedure. The N terminal amino acid sequence of the two proteins was determined and the results confirmed that the two forms were IF2 alpha and -beta, both encoded by the infB gene. The N-terminal amino acid sequence determined for IF2 beta is Met94-Gln-Asn Asn-Gln-Phe. The presence of methionine at position 94 shows that this form is, in fact, the result of a second translational initiation in infBB.su mRNA, since the codon at amino acid position 94 is GUG, which is the normal codon for valine, but also known to be an initiator codon. This is a new example of the unusual tandem translation in E. coli of an open mRNA reading frame. PMID- 1426243 TI - Production of an antiserum specific to the ADP-ribosylated form of elongation factor 2 from archaebacteria and eukaryotes. AB - An antiserum to ADP-ribosylated elongation factor 2 (ADPR-EF-2) from S. acidocaldarius was raised in rabbits using stained, homogenized, ADPR-EF-2 containing slices from SDS-gels as a source of antigen. Elongation factor 2 (EF 2) from S. acidocaldarius was cloned in E. coli and the expressed gene product was used in order to adsorb all anti-EF-2 antibodies which do not contain the ADP ribosyl group within their epitopes, as E. coli is unable to synthesize the ADP ribosyl acceptor diphthamide. The remaining antibodies were specific to ADP ribosylated EF-2 from Thermoplasma acidophilum, S. acidocaldarius and Desulfurococcus mucosus. ADP-ribosylated EF-2 from eukaryotic sources also reacted with the adsorbed antiserum as shown for EF-2 isolated from the killi fish Cynolebias whitei, the mouse species BALB/c and Han/Wistar rats. The adsorbed antiserum did not cross-react with ADP-ribosylated actin or rho protein or with FAD-containing D-amino acid oxidase. PMID- 1426244 TI - 13C NMR studies of complexes of Escherichia coli dihydrofolate reductase formed with methotrexate and with folic acid. AB - 13C NMR studies of 13C-labelled ligands bound to dihydrofolate reductase provide (DHFR) a powerful means of detecting and characterizing multiple bound conformations. Such studies of complexes of Escherichia coli DHFR with [4,7,8a,9 13C]- and [2,4a,6-13C]methotrexate (MTX) and [4,6,8a-13C]- and [2,4a,7,9 13C]folic acid confirm that in the binary complexes, MTX binds in two conformational forms and folate binds as a single conformation. Earlier studies on the corresponding complexes with Lactobacillus casei DHFR indicated that, in this case, MTX binds as a single conformation whereas folate binds in multiple conformational forms (both in its binary complex and ternary complex with NADP+); two of the bound conformational states for the folate complexes are very different from each other in that there is a 180 degrees difference in their pteridine ring orientation. In contrast, the two different conformational states observed for MTX bound to E. coli DHFR do not show such a major difference in ring orientation and bind with N1 protonated in both forms. The major difference appears to involve the manner in which the 4-NH2 group of MTX binds to the enzyme (although the same protein residues are probably involved in both interactions). Addition of either NADP+ or NADPH to the E. coli DHFR-MTX complex results in a single set of 13C signals for bound methotrexate consistent with only one conformational form in the ternary complexes. PMID- 1426245 TI - Prothymosin alpha is phosphorylated by casein kinase-2. AB - Prothymosin alpha (ProT alpha) is a 12.5 kDa acidic polypeptide that is considered to have a nuclear function related to cell proliferation. Inspection of its amino acid sequence revealed the presence of sequences that may serve as targets for phosphorylation by casein kinase-2 (CK-2). ProT alpha isolated from calf thymocytes was phosphorylated in vitro by CK-2. The phosphorylation sites are Ser and Thr residues located among the first 14 amino acid residues in the ProT alpha sequence. Another site that is theoretically suitable for phosphorylation by CK-2, at the C-terminus of the polypeptide, is not, in fact, phosphorylated. Thymosin alpha 1 (T alpha 1), a peptide whose sequence corresponds to the first 28 amino acids of ProT alpha, is also phosphorylated by CK-2 at the same phosphorylation sites as ProT alpha. In cultured splenic lymphocytes ProT alpha was phosphorylated at Thr residues located at positions 7, 12 and/or 13. Based on these observations we conclude that CK-2, or another cellular kinase with similar sequence specificity, is responsible for phosphorylation of ProT alpha in vivo. PMID- 1426246 TI - Expression of functional Thermoplasma acidophilum proteasomes in Escherichia coli. AB - The two genes encoding the constituent subunits of the Thermoplasma acidophilum proteasome were expressed in Escherichia coli yielding fully assembled molecules as shown by electron microscopy. The recombinant proteasomes were purified to homogeneity and were shown to have proteolytic activity indistinguishable from proteasomes isolated from T. acidophilum. PMID- 1426248 TI - Expression of human collagen type IV genes is regulated by transcriptional and post-transcriptional mechanisms. AB - The molecules of the basement membrane specific collagen type IV are heterotrimers consisting of two alpha 1(IV) and one alpha 2(IV) polypeptide chains. Comparison of the ratios of transcription by nuclear run-on analysis and mRNAs by RNAse protection assay indicates the involvement of transcriptional as well as post-transcriptional events in the control of overall collagen type IV expression. The relative ratios of transcription of the respective genes COL4A1 and COL4A2 remained near 2:1 in most cells, whereas the ratio of mRNA steady state levels alpha 1(IV)/alpha 2(IV) varied from 0.3:1 to 1:1 and did not parallel the subunit structure of the protein. Nevertheless, secreted protein shows a 2:1 ratio of the subunit polypeptides. This indicates that post translational processes during chain selection, aggregation and secretion finally determine the amount of secreted protein. PMID- 1426247 TI - Lamin A gene expression is specifically suppressed in v-src-transformed cells. AB - By a differential screening procedure, we have obtained several cDNAs the expression of which was down-regulated in v-src-transformed 3Y1 cells compared to parental 3Y1 cells. One of these cDNAs, termed N26, was extensively analyzed. Sequence analysis revealed that N26 cDNA was 3,095 nucleotides in length and contained an open reading frame of 665 amino acid residues. Based on an homology search at the nucleotide level, it was postulated that N26 gene encodes lamin A. The expression of the N26 gene was not suppressed in other types of transformed cells, such as v-mos-, v-ras- and SV40-transformed 3Y1 cells. PMID- 1426249 TI - Loss of transcription factor AP-1 DNA binding activity during lymphocyte aging in vivo. AB - The main feature of cellular senescence is cessation of cell proliferation. Protooncogene c-fos, which is required for the cell to enter into DNA synthesis, is repressed in senescent fibroblasts. Diminished expression of c-fos and impaired formation of AP-1, which is a complex of c-Fos and c-Jun proteins acting as a transcription factor, was found in lymphocytes derived from old (> 18 months) mice and stimulated with Con A. There were no differences in c-jun expression and formation of other transcription factors (AP-2 and AP-3) between lymphocytes isolated from old and young mice. PMID- 1426251 TI - Noradrenaline release from permeabilized synaptosomes is inhibited by the light chain of tetanus toxin. AB - Noradrenaline release from rat brain cortical synaptosomes permeabilized with streptolysin O can be triggered by microM concentrations of free Ca2+. This process was inhibited within minutes by tetanus toxin and its isolated light chain, but not by its heavy chain. The data demonstrate that the effect of tetanus toxin on NA release from purified synaptosomes is caused by the intraterminal action of its light chain. PMID- 1426250 TI - Characterisation of the expression and post-translational processing of the preprotachykinin-I gene and the regulated release of tachykinins by the RINm5F cell-line. AB - Normal transcription and postranslational processing of the preprotachykinin (PPT)-I gene and regulated release of substance P and neurokinin A by the rat pancreatic endocrine cell-line, RINm5F, has been demonstrated, using radioimmunoassays (RIAs), reversed-phase (rp)HPLC and Northern blot analysis. This is the first stable cell-line found to express the PPT-I gene and provides an opportunity for investigating PPT-I gene expression and tachykinin biosynthesis. RIN5mF cells are a model for the pancreatic beta-cell, which is not known to exhibit PPT-I gene expression which may, therefore, be a feature of the transformed state of these cells. These data may imply that the tachykinins are important in pancreatic islet embryogenesis. PMID- 1426252 TI - Biochemical properties of rat protein kinase C-eta expressed in COS cells. AB - Using a PKC-epsilon cDNA probe a cDNA for PKC-eta has been cloned from a rat lung cDNA library. When expressed in COS cells, rat PKC-eta appeared as an 84 kDa protein. PKC-eta expressed in COS cells, was solubilized by 1% Triton X-100 and purified away from the endogenous PKC-alpha by ammonium sulphate fractionation. The activity of this PKC-eta preparation was characterized with respect to cofactor dependence and substrate specificity. Various PKC pseudosubstrate peptides are phosphorylated by PKC-eta in a phospholipid and TPA-dependent but calcium-independent manner. The polypeptide histone IIIS is a poor substrate. PMID- 1426253 TI - New mouse 5-HT2-like receptor. Expression in brain, heart and intestine. AB - A novel member of the family of G protein-coupled receptors has been isolated from a mouse brain cDNA library by screening with polymerase chain reaction (PCR) generated fragment of mouse genomic DNA amplified using degenerated primers. Sequence comparison demonstrates that the encoded protein sequence shows the highest homology to the 5-HT2 family of receptors. The pharmacological profile of membranes from COS cells transfected with this cDNA, corresponds to a new 5-HT2 like receptor that we propose to call 5-HT2C. Its major sites of expression are in the mouse intestine and heart, also with detectable expression in brain and kidney. We speculate that it could account at least in part for the 'atypical' functions attributed to the 5-HT1C/5-HT2 receptors. PMID- 1426254 TI - Carbohydrate binding specificity of the Tn-antigen binding lectin from Vicia villosa seeds (VVLB4). AB - 2-Dansylamino-2-deoxy-D-galactose (GalNDns) is a useful fluorescent probe to study the interaction of non-fluorescent sugars with the B4 lectin from Vicia villosa seeds (VVLB4). Binding of the lectin to GalNDns leads to a 5.2-fold increase in Dansyl fluorescence with a concomitant 10 nm blue shift in its emission maximum. The strong binding of GalNDns (Ka = 7.33 x 10(4) M-1 at 20 degrees C) is due to a favourable entropic contribution to the association process. Among the other sugars studied, GalNAc alpha 1-O-Ser followed by Me alpha GalNAc are the best ligands. 2-Deoxygalactose, galactosamine and galactose are 2013, 469 and 130 times weaker ligands, respectively, as compared to GalNAc, whereas GalNDns is about 2.44 times more potent than GalNAc, indicating that substitutions at the C-2 position of GalNAc have a considerable influence on the binding affinities. Equatorial orientation of the hydroxyl group at C-3 and axial orientation at C-4 as in galactose are important for the interaction with VVLB4. The C-6 hydroxyl group is not indispensable. The binding site of the lectin is directed exclusively towards monosaccharides alone. Interestingly enough, despite its preference for Me alpha GalNAc over Me beta GalNAc, in oligosaccharides, the lectin prefers terminal beta-linked GalNAc as compared to the alpha-linked one. PMID- 1426255 TI - Molluscan putative prohormone convertases: structural diversity in the central nervous system of Lymnaea stagnalis. AB - In the cerebral ganglia of the central nervous system of the freshwater snail Lymnaea stagnalis many neuropeptides are proteolytically processed from larger prohormones at sites marked by both single and multiple basic amino acids. In the present study we identified cloned cDNA and PCR products corresponding to three putative endoproteases that may be involved in prohormone processing. The cDNA encodes a protein of 653 residues with an overall sequence identity of 60%, 41%, 35%, 40%, and 27% with the recently characterized endoproteases PC2, PC1/3, PC4, furin and Kex2, respectively. The Lymnaea preproconvertase has approximately 80% homology with the catalytic domain, and approximately 40% and approximately 50% with the N- and C-terminal part, respectively, of the vertebrate PC2. Two cloned PCR products, Lfur 1 and Lfur 2, show highest sequence identity to furin. Expression of the LPC2 gene is exclusively in the central nervous system, where two LPC2 transcripts of 3.0 and 4.8 kb were detected. PMID- 1426256 TI - Synthesis and characterization of a 25-residue rubredoxin(II)-like metalloprotein and its valine-leucine mutant. AB - An iron-sulfur metalloprotein containing the 5-12 and 35-50 residues of Desulfovibrio gigas rubredoxin has been synthesized by Fmoc solid phase peptide synthesis and subsequent peptide folding. A Gly links the two residue chains between Val-5 and Glu-50. Sybyl Tripos structure optimization indicates only minor structural changes of the folded synthetic protein compared to the similar residue positions in the native protein. The UV-VIS spectrum of the reduced synthetic protein is very similar to that of native D. gigas rubredoxin and the molecular mass determined by laser mass spectrometry has the expected value (+/- 2D). No metal is transferred to the gas phase by the laser beam merely by mixing the peptide and iron(II), substantiating that the folding procedure is a necessary pre-requisite for protein formation. The Val-->Leu41 chemical mutant has also been synthesized and behaves in a closely similar fashion. PMID- 1426257 TI - The gamma-subunit of the principal G-protein from squid (Loligo forbesi) photoreceptors contains a novel N-terminal sequence. AB - The squid (Loligo forbesi) visual system presents as accessible a system for study of G-protein mediated signal transduction as the vertebrate rod outer segment with the added advantage that the major G-protein is a member of the Gq class. Here the cDNA clone encoding the gamma-subunit of this G-protein is reported, thereby completing the molecular cloning of the heterotrimeric G protein. The deduced protein structure of G-gamma has relatively little sequence identity with known mammalian counterparts particularly in comparison with the relatively high degree found for both the alpha- and beta-subunits of this protein. In particular, the N-terminus of the squid visual G-gamma contains a repetitive, highly charged region, rich in lysine and glutamate, that has no parallel in other G-proteins. The amino acid sequence of a number of peptides derived by chemical cleavage of G-gamma accounted for much of the protein sequence predicted from the cDNA, including the unusual N-terminal region. PMID- 1426258 TI - Primary structure required for the inhibition of smooth muscle myosin light chain kinase. AB - Myosin light chain kinase (MLCK) contains the autoinhibitor sequence right next to the N-terminus side of the calmodulin binding region. In this paper, the structural requirement of the inhibition of MLCK activity was studied using synthetic peptide analogs. Peptides Ala-783-Lys-799 and Ala-783-Arg-798 inhibited calmodulin independent MLCK at the same potency as the peptide Ala-783-Gly-804. Deletion of Arg-797-Lys-799 or substitution of these residues to Ala markedly increased the Ki while the substitution of Lys-792 and Lys-793 to Ala and the deletion of Lys-784-Lys-785 did not affect the inhibitory activity of the peptides. The results suggest that Arg-797-Arg-798 are especially important for the inhibitory activity among other basic residues in the autoinhibitory region. PMID- 1426259 TI - A critical role of protein-bound water in the catalytic cycle of cytochrome P-450 camphor. AB - The rates of NADH oxidation during the hydroxylation of camphor by cytochrome P 450cam were followed in the presence of co-solvents used to increase the osmotic pressure surrounding the protein-bound water. As a result, the measured Vmax decreases independently of the perturbant tested. Roughly 28 molecules of water, involved during the catalytic cycle, are deduced from the variation of Vmax as a function of osmotic pressure. These molecules, in part, could be those present in the cytochrome P-450cam-putidaredoxin interface. PMID- 1426260 TI - Gelation of liposome interior. A novel method for drug encapsulation. AB - Liposomes can be loaded with weak acids and bases, which exist in solutions in equilibrium with membrane permeable uncharged form, using various gradients across their membranes. Because in some cases the estimated drug concentration in the loaded liposomes exceeds their aqueous solubility we investigated the physical state of the liposome encapsulated anticancer drug Doxorubicin. X-Ray diffraction, electron microscopy, and test tube solubility experiments have shown that upon encapsulation the drug molecules form a gel-like phase. PMID- 1426261 TI - The role of conserved aspartate and serine residues in ligand binding and in function of the 5-HT1A receptor: a site-directed mutation study. AB - Wild-type and mutant serotonin 1A receptors were transiently expressed in COS-7 cells using the infection-transfection variant of the vaccinia virus/T7 polymerase vector system. The amino acid substitutions in the transmembrane regions, Asp82-->Asn82, Asp116-->Asn116, and Ser198-->Ala198 all resulted in a decrease in affinity for 5-HT by 60-100-fold, without affecting the affinity for the antagonist, pindolol. The binding of agonist to the additional mutant, Thr199 ->Ala199, was too weak to be measured, 5-HT induced GTPase activities for all receptors studied. These findings indicate that the residues mutated play an important role in the binding of the agonist and less critical roles in the binding of the antagonist pindolol. PMID- 1426262 TI - Utrophin, the autosomal homologue of dystrophin, is widely-expressed and membrane associated in cultured cell lines. AB - Utrophin, the autosomal dystrophin-related protein (DRP), is expressed in HeLa cells, smooth muscle-like BC3H1 cells from mouse brain, COS monkey kidney cells, the P388D1 monocyte-macrophage cell line and untransformed human skin fibroblasts, as well as in rat C6 glioma and Schwannoma cells. It was undetectable, however, in the Sp2/O mouse myeloma cell line and in hybridoma lines derived from it. Dystrophin was not detected in any of these cell lines. Although all utrophin-containing cells were capable of forming monolayers in culture, no major effects of either attachment to substratum or length of time in culture (2-17 days) on utrophin levels were observed. After subcellular fractionation of BC3H1 or glioma cells, nearly all of the utrophin was found in the Triton-soluble fraction, suggesting an association with cell membranes. PMID- 1426263 TI - Transport of proteins into the various subcompartments of mitochondria. AB - The import of proteins into mitochondria is an intricate process comprised of multiple steps. The first step involves the sorting of cytosolically synthesized precursor proteins to the mitochondrial surface. There precursor proteins are recognized by specific receptors which deliver them to the general import site present in the outer membrane. The second stage of import involves a series of complex intraorganelle sorting events which results in the delivery of the proteins to one of the four possible submitochondrial destinations, namely the outer and inner membranes, the matrix and intermembrane space. Here in this review, we discuss the current knowledge on these intramitochondrial sorting events. We especially focus on targeting of proteins to the intermembrane space. Sorting to the intermembrane space represents a particularly interesting situation, as at least three separate targeting pathways to this subcompartment are known to exist. PMID- 1426264 TI - Low translational efficiency of the F1-ATPase beta-subunit mRNA largely accounts for the decreased ATPase content in brown adipose tissue mitochondria. AB - The half-life of the F1-ATPase beta-subunit (F1-beta) mRNA in ATPase-poor brown adipose tissue (BAT) (t1/2 = 9.5 h) was found to be 3-7-fold shorter than in liver (t1/2 = 27 h) and heart (t1/2 = 63 h) of mice. When translated in reticulocyte lysate, a 2-3-fold lower efficiency appeared with F1-beta mRNA from BAT than from other tissues. The in vitro synthesized F1-beta protein precursors of BAT, liver and heart origin were imported and processed by mouse liver mitochondria with equal efficiency. The results indicate that the pool of abundant F1-beta mRNA in BAT is not fully translatable, most likely due to its low metabolic stability. PMID- 1426265 TI - Photoaffinity labeling of DNA polymerase alpha DNA primase complex based on the catalytic competence of a dNTP reactive analog. AB - FABdCTP was found to be a substrate of DNA polymerization catalyzed by a DNA polymerase alpha-DNA primase complex on the 5'-GTGAGTAAGTGGAGTTTGGCACGAT-3' template and 3'-CTCAAACCGT-5' primer. After complete primer extension in the presence of FABdCTP under UV-irradiation of the reaction mixture, 70% of the template was covalently linked to the primer. Labeling of the 165 kDa subunit of the DNA polymerase alpha, 59 kDa and 49 kDa subunits of the DNA primase and an unknown protein with apparent molecular weight of 31 kDa was observed. By another way of protein labeling FABdCTP was covalently bound to the subunits of the enzyme under UV irradiation and then this moiety was introduced into the 3'-end of the 5'-[32P]primer by the catalytic activity of DNA polymerase or DNA primase. In this case covalent labeling of the 165 kDa, 49 kDa and 31 kDa subunits was observed. PMID- 1426266 TI - m-iodobenzylguanidine increases the mitochondrial Ca2+ pool in isolated hepatocytes. AB - The incubation of isolated hepatocytes with the inhibitor of protein mono ADP ribosylation, m-iodobenzylguanidine (MIBG), resulted in an increase in the size of the mitochondrial Ca2+ pool, without alteration of the non-mitochondrial Ca2+ store(s). This increase was abolished when the cytosolic free Ca2+ concentration ([Ca2+]i) was buffered by prior loading of the cells with fluo 3. Elevating [Ca2+]i by releasing the endoplasmic reticular Ca2+ store with 2,5-di-(tert butyl)-1,4-hydroquinone resulted in a synergistic increase in the magnitude of the mitochondrial Ca2+ pool. A role for protein ADP-ribosylation in the intracellular regulation of mitochondrial Ca2+ homeostasis is suggested. PMID- 1426267 TI - Angiotensin-II-induced expression of proto-oncogene (c-fos, jun-B and c-jun) mRNA in bovine adrenocortical fasciculata cells (BAC) is mediated by AT-1 receptors. AB - We have shown previously that angiotensin-II (A-II) controls proto-oncogene (c fos, jun-B and c-jun) mRNA accumulation in bovine adrenal fasciculata cells (BAC). Since BAC contain both subtypes (AT-1 and AT-2) of the A-II receptor, we have investigated which subtype was involved in the effect of A-II on proto oncogene mRNA by using a selective antagonist for AT-1 (DUP 753) and for AT-2 (CGP 42112A). DUP 753, but not CGP 42112A, inhibited the stimulatory effect of A II on proto-oncogene mRNA, with ID50s of 4 x 10(-7) M, 7 x 10(-7) M and 2 x 10( 6) M for c-fos, jun-B and c-jun, respectively. Neither of the two antagonists by themselves had a direct effect on proto-oncogene mRNA. As the A-II AT-1 receptors are coupled to the phospholipase C system in BAC, we have investigated whether the A-II effects on the proto-oncogenes were mediated by protein kinase C (PKC) or by Ca2+ calmodulin. First, activation of PKC by the phorbol ester, PMA, increased the level of three proto-oncogene mRNAs, whereas calcium ionophore had no effect. Second, staurosporine, a specific inhibitor of PKC, reduced the stimulatory action of A-II on proto-oncogene mRNA by 80-90%, whereas trifluoroperazine, an inhibitor of calmodulin, had no significant effect. These results demonstrate that the effects of A-II on proto-oncogene mRNA are mediated by AT1 receptor subtypes, mainly through activation of the PKC pathway. PMID- 1426268 TI - Induction of cytokines in glial cells by trans activator of human T-cell lymphotropic virus type I. AB - Human T-cell lymphotropic virus type I (HTLV-I), the cause of adult T-cell leukemia, is also associated with the neurological disease, TSP/HAM (tropical spastic paraparesis/HTLV-I associated myelopathy). The HTLV-I genome encodes a protein, Tax, that trans activates viral and cellular gene transcription. To understand the mechanisms for the production of cytokines by HTLV-I in nervous tissue, we examined their expression in glial cells which carried the Tax expressing vector. We demonstrated that Tax expression enhanced the production by glial cells of interleukin (IL)-1, IL-6, granulocyte-macrophage colony stimulating factor (GM-CSF) and transforming growth factor (TGF) beta. We suggest that the excessive production of cytokines in nervous tissue may play a role in pathogenesis of TSP/HAM. Glial cells that carry the tax gene may provide a model useful for in vitro study of the mechanism of production of cytokines in the nervous system. PMID- 1426269 TI - Cyclosporin A protects pancreatic islet cells from nitric oxide-dependent macrophage cytotoxicity. AB - It has been shown earlier in an in-vitro model of inflammatory islet cell death that activated macrophages lyse islet cells via the release of nitric oxide. Here we report that cyclosporin A suppresses macrophage cytotoxicity. Control experiments showed that the immunosuppressive drug does not improve the defences of islet cells against nitric oxide but inhibits the release of nitric oxide from LPS-stimulated macrophages. This property of cyclosporin A may contribute to the preservation of beta cell function seen in cyclosporin A-treated patients with recent onset type I diabetes. PMID- 1426270 TI - Interaction of nitrogen dioxide with human plasma. Antioxidant depletion and oxidative damage. AB - Nitrogen dioxide (NO2.) is often present in inhaled air and may be generated in vivo from nitric oxide. Exposure of human blood plasma to NO2. caused rapid losses of ascorbic acid, uric acid and protein thiol groups, as well as lipid peroxidation and depletions of alpha-tocopherol, bilirubin and ubiquinol-10. No increase in protein carbonyls was detected. Supplementation of plasma with ascorbate decreased the rates of lipid peroxidation, alpha-tocopherol depletion and loss of uric acid. Uric acid supplementation decreased rates of lipid peroxidation but not the loss of alpha-tocopherol. We conclude that ascorbic acid, protein -SH groups, uric acid and alpha-tocopherol may be important agents protecting against NO2. in vivo. If these antioxidants are depleted, peroxidation of lipids occurs and might contribute to the toxicity of NO2.. PMID- 1426271 TI - DNA binding of histone H1 is modulated by nucleotides. AB - Histone H1 acts as a general repressor of transcription in eukaryotes by organizing nucleosomes into inaccessible condensed forms of chromatin. The capability of H1 to bind to DNA with some sequence specificity is likely to be critical in the control of these processes. We show here that ATP and several other nucleotides, including non-hydrolyzable derivatives, can inhibit DNA binding of H1. The results also show that ATP differentially affects binding of H1 to DNA in a fashion enhancing nucleotide sequence specificity of the binding. The study suggests a novel mechanism of modulation of H1 activity that has important implications for the role of H1 as a transcriptional regulator. PMID- 1426272 TI - Stilbene synthase from Scots pine (Pinus sylvestris). AB - Stilbene synthases are named according to their substrate preferences. By this definition, enzymes preferring cinnamoyl-CoA are pinosylvin synthases, and proteins with a preference for phenylpropionyl-CoA are dihydropinosylvin synthases. We investigated the assignment of a stilbene synthase cloned from Scots pine (Pinus sylvestris) as dihydropinosylvin synthase and the proposal of an additional pinosylvin synthase [1992, Plant Mol. Biol. 18, 489-503]. The results show that the previous interpretation was misled by several unexpected factors. Firstly, we found that the substrate preference and the activity of the plant-specific protein expressed in E. coli was influenced by bacterial factors. This was reduced by improvement of the expression system, and the subsequent kinetic analysis revealed that cinnamoyl-CoA rather than phenylpropionyl-CoA is the preferred substrate of the cloned stilbene synthase. Secondly, mixing experiments showed that extracts from P. sylvestris contain factor(s) which selectively influenced the substrate preference, i.e. the activity was reduced with phenylpropionyl-CoA, but not with cinnamoyl-CoA. This explained the apparent differences between plant extracts and the cloned enzyme expressed in E. coli. Taken together, the results indicate that the cloned enzyme is a pinosylvin synthase, and there is no evidence for a second stilbene synthase. This study cautions that factors in the natural and in new hosts may complicate the functional identification of cloned sequences. PMID- 1426273 TI - Complementary DNA sequences of two 14.5 kDa subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Completion of the primary structure of the complex? AB - The amino acid sequences of two nuclear-encoded subunits of complex I from bovine heart mitochondria have been determined. Both proteins have an apparent molecular weight of 14.5 kDa and their N-alpha-amino groups are acetylated. They are known as subunits B14.5a and B14.5b. Neither protein is evidently related to any known protein and their functions are obscure. A total of 34 nuclear-encoded subunits of bovine complex I have now been sequenced and it is thought that the primary structure of the complex is now complete, although with such a complicated structure it is difficult to be certain that there are no other subunits remaining to be sequenced. Seven additional hydrophobic subunits of the enzyme are encoded in mitochondrial DNA, and therefore bovine heart complex I is an assembly of about 41 different proteins. If it is assumed that there is one copy of each protein in the assembly, these polypeptides contain 7,955 amino acids in their sequences, more than are found in the Escherichia coli ribosome, which contains 7,336 amino acids in its 32 polypeptides. PMID- 1426274 TI - Photolabeling of the phosphate binding site of chloroplast coupling factor 1 with [32P]azidonitrophenyl phosphate. AB - Chloroplast F1-ATPase (CF1) was photolabeled by a radiolabeled photoactivatable derivative of Pi, 4-azido-2-nitrophenyl [32P]phosphate (ANPP). The radioactivity was localized in the beta subunit of CF1. Upon cleavage of the beta subunit by cyanogen bromide, the predominantly labeled peptide was recovered, which was subsequently subjected to tryptic digestion. A tryptic peptide (spanning Ile312 Arg354), was found to contain nearly all the covalently bound radioactivity. By Edman degradation, the labeled amino acid residues were identified as Tyr328, Val329 and Pro330. The labeled beta-Tyr328 of CF1 is the equivalent of beta Tyr311 of F1 from beef heart mitochondria, which was previously found to be photolabeled by ANPP [J. Garin et al. (1989) Biochemistry 28, 1442-1448]. PMID- 1426276 TI - Half-life of ubiquinone-9 in rat tissues. AB - The half-life of ubiquinone-9 in various rat tissues was determined. Rats were injected intraperitoneally with [3H]mevalonate and the decay of radioactivity incorporated into ubiquinone-9 was followed using reverse-phase HPLC. The half life varied between 49 h (testis) and 125 h (kidney). PMID- 1426275 TI - Primary structure of frog rhodopsin. AB - Amphibians have been employed extensively to study the anatomy, physiology, biochemistry, and cell biology of the visual system for decades, yet there have been no reports concerning the primary structure of amphibian visual transduction components. Thus, we have determined the entire nucleotide sequence of frog (Rana pipiens) rhodopsin cDNA, including a putative transcription start point and poly A tail, by sequence analysis of PCR products and mRNA. The open reading frame predicts an opsin of 354 residues, six residues longer than the mammalian rod opsins, containing 11 potential phosphorylation sites in the C-terminal domain. RNA blot analysis revealed two transcripts of ca. 1.7 and 3.1 kb. Frog rhodopsin exhibits approximately 85% identity to mammalian rhodopsin at the amino acid level. Sequence analysis of additional components will produce the framework from which a more detailed understanding of amphibian phototransduction can emerge. PMID- 1426277 TI - Dissociation of store release from transmembrane influx of calcium in human neutrophils. AB - Release of Ca2+ from intracellular stores was visualised in individual neutrophils in the presence of the Mn2+ or SKF 96365. Influx of Mn2+ quenched fura-2 close to the plasma membrane but did not quench fura-2 at the site of store release. The size and location of the 'cloud' of elevated Ca2+ was unaffected by the channel blocker SKF 96365. Furthermore, the size and location was unaffected by the presence of extracellular Ca2+. This dissociation of transmembrane influx from store release demonstrates that the entry of Ca2+ into the cytosol of neutrophils occurs directly into the cytosol and not via the store site. PMID- 1426278 TI - Glucose decreases respiratory control ratio in EL-4 tumor cells. AB - EL-4 ascites thymoma cells are shown to have high aerobic glycolysis and decreased Pasteur effect. At the same time, glucose produces a much smaller inhibitory effect on cell respiration (Crabtree effect) than in Ehrlich ascites carcinoma (EAC) cells. In intact EL-4 cells, the respiratory control ratio (RCR) was found to be 6.2 with endogenous substrates and 8.0 with glutamine. Glucose decreased the RCR to 3.2, by stimulating the state 4 respiration. In rat thymocytes and EAC cells, such an effect of glucose was absent (RCR of 7.0 and 7.2, respectively). It is suggested that in EL-4 tumor cells, the high aerobic glycolysis and small Crabtree effect may be due to glucose-induced 'uncoupling' of oxidation and phosphorylation. PMID- 1426279 TI - Platelet-derived endothelial cell growth factor. Pharmacokinetics, organ distribution and degradation after intravenous administration in rats. AB - Platelet-derived endothelial cell growth factor (PD-ECGF) stimulates chemotaxis of endothelial cells in vitro and has angiogenic activity in vivo. Recently PD ECGF was shown to have thymidine phosphorylase activity. In order to study possible therapeutic applications of PD-ECGF we used a rat model to determine its pharmacokinetics and tissue distribution after intravenous injection. [125I]PD ECGF disappeared from the plasma in a biphasic manner, with estimated distribution and elimination half-lives of 17 min and 7 h, respectively. PD-ECGF was metabolized in the liver, excreted via the bile, and not accumulated in any organ system. The stability and long half-life in the circulation, together with the specificity for endothelial cells, suggest that PD-ECGF may be useful as a therapeutic agent to stimulate re-endothelialization in vivo, or, in view of its thymidine phosphorylase activity, in chemotherapy, by decreasing the pool of available thymidine. PMID- 1426280 TI - Codon-anticodon pairing. A model for interacting codon-anticodon duplexes located at the ribosomal A- and P-sites. AB - The interaction between two codon-anticodon duplexes of the ribosomal A- and P site-bound tRNAs is the key feature of the proposed model. This interaction prohibits non-canonical base pairing at the first and second positions of the codon and controls base pairing at the third position (wobbling rules ensuing from the model are in good accord with those generated from experiments). The model is capable of predicting codon context effects. It follows from the model that modifications of the first anticodon residue of the P-site tRNA can affect the stability of the A-site duplex, and that the translation of a DNA single chain analogue of mRNA should be accompanied by non-canonical base pairing at all three positions of the codon. These predictions of the model can be subjected to experimental tests. PMID- 1426281 TI - ATP-sensitive K(+)-channels in the human adult ventricular cardiomyocytes membrane. AB - Using the patch-clamp method in 27 different inside-out patches it was shown for the first time that they defined the basic parameters of the functioning of single ATP-sensitive K+ channels in the human adult ventricular cardiomyocytes membrane. At [K+]o = 140 mM single channel conductance (over the linear part of the I-V relation) reaches 100 pS. The possibility of the existence of these channels' conductance sublevels as well as the cluster character of their localization in sarcolemma is shown. The channel activity demonstrates an obvious run-down with tau at about a minute. The analysed channels possess one open and two closed states. PMID- 1426282 TI - Transcriptional- and post-transcriptional-dependent regulation of glutathione S transferase expression in rat hepatocytes as a function of culture conditions. AB - Transcriptional activity of the glutathione S-transferase (GST) alpha (subunits 1 and 2), mu (subunits 3 and 4) and pi (subunit 7) gene families has been analyzed using the nuclear 'run-on' technique on adult rat hepatocytes maintained for 4 days in conventional culture and for 4 and 12 days in co-culture with rat liver epithelial cells. Several medium conditions are included in this study, namely with or without fetal calf serum and with nicotinamide or dimethylsulphoxide. Hepatocytes co-cultured for 4 days maintain approximately 30-70% of the alpha gene family transcriptional activity, whatever the medium conditions, when compared to freshly isolated hepatocytes. A marked decrease is observed after 12 days of co-culture or when hepatocytes are maintained in conventional culture. The transcriptional activity of the mu gene family is maintained at 40-160% when hepatocytes are cultured with or without fetal calf serum, and is inducible by nicotinamide (approximately 4-fold) and dimethylsulphoxide (approximately 2-fold) in conventional culture and/or in co-culture. In contrast to freshly isolated hepatocytes, GST pi gene transcriptional activity is observed in conventional and co-cultured hepatocytes, irrespective of the medium conditions. Dimethylsulphoxide treatment however, represses the expression of GST 7 in vitro. These results demonstrate that the expression of GST alpha, mu and pi genes in conventional and co-cultured rat hepatocytes is controlled primarily at the level of transcription. It cannot be excluded, however, that dimethylsulphoxide stabilizes the GST mRNA levels in vitro. PMID- 1426283 TI - Altered expression of G-protein mRNA in spontaneously hypertensive rats. AB - We have recently demonstrated that the decreased ability of hormones, forskolin and GTP to stimulate adenylate cyclase in heart and aorta from spontaneously hypertensive rats (SHR), as compared to their age-matched Wistar-Kyoto control rats (WKY), was associated with enhanced levels of Gi- and not with Gs-regulatory proteins. In the present studies we have investigated the expression of Gi regulatory proteins at the mRNA level by Northern blotting. Total RNA of heart ventricle and aorta from WKY and SHR was probed with radiolabeled cDNA inserts encoding Gi alpha-2 and Gi alpha-3. The Gi alpha-2 and Gi alpha-3 probes detected a message of 2-3 and 3-5 kb, respectively, in both WKY and SHR, however, the message was significantly enhanced in SHR, as compared by WKY. On the other hand the cDNA probe encoding Gs alpha detected a message of 1.8 kb in heart and aorta from both WKY and SHR, however, no difference in the levels of Gs alpha mRNA was detected in SHR and WKY tissues. These results indicate that the mRNA levels of Gi alpha-2 and Gi alpha-3 and not of Gs are overexpressed in heart and aorta from SHR, which may be responsible for the increased levels of Gi as shown earlier by immunoblotting techniques. It may be suggested that the enhanced vascular tone and impaired cardiac contractility in hypertension may partly be the consequences of increased levels of Gi in heart and aorta. PMID- 1426284 TI - Primary structure of a cardioactive neuropeptide from the tobacco hawkmoth, Manduca sexta. AB - The amino acid sequence of the first of a family of insect cardioregulatory peptides from the tobacco hawkmoth, Manduca sexta, has been determined using a combination of Edman degradation microsequencing and mass spectroscopy. This peptide contains 9 amino acid residues and an observed mass for the monoisotopic protonated molecule of 956.4 Da. There are two cysteines at positions 3 and 9 forming a disulfide bridge and the carboxyl-terminus is amidated. The structure of this peptide, Pro-Phe-Cys-Asn-Ala-Phe-Thr-Gly-Cys-NH2, is identical to a peptide recently isolated from crabs called crustacean cardioactive peptide (CCAP) and we propose that this peptide be named Manduca CCAP. PMID- 1426285 TI - Ca(2+)-mediated interaction between negatively charged and neutral liposomes. AB - In the present work it is shown that large unilamellar lecithin/cholesterol liposomes are able to sequester small negatively charged liposomes in the presence of divalent cations. Evidence is presented suggesting that the sequestration occurs via the formation of membrane invaginations transformed further into intraliposomal vesicles. PMID- 1426286 TI - A subgroup of class alpha glutathione S-transferases. Cloning of cDNA for mouse lung glutathione S-transferase GST 5.7. AB - A full-length cDNA clone encoding the previously purified mouse glutathione S transferase GST 5.7 [(1991), Biochem. J. 278, 793-799] has been isolated from a mouse lung cDNA library in lambda gt11. Sequencing of the clone revealed the presence of microheterogeneity in GST 5.7. Comparison of the deduced protein sequence with other glutathione S-transferases, together with previous information available on GST 5.7, indicates that the enzyme belongs to a novel subgroup within the alpha class of glutathione S-transferases. Members of the subgroup, which also include the rat GST 8-8 and perhaps chicken GST CL3, show high sequence homology with each other, but only moderate similarity to other alpha class enzymes. They share a substrate specificity profile that resembles pi class enzymes, and are active in the conjugation of lipid peroxidation products. PMID- 1426287 TI - In vivo phosphorylation of the 30-kDa protein of tobacco mosaic virus. AB - The 30-kDa protein of tobacco mosaic virus, which is involved in cell-to-cell movement function, is phosphorylated in tobacco protoplasts. To investigate which portion of the protein is phosphorylated we inoculated several truncated 30-kDa protein mutants into protoplasts and determined whether or not those truncated proteins are phosphorylated. The results showed that amino acid residues 234-261 of the 30-kDa protein are required for this phosphorylation. PMID- 1426288 TI - Activity, disulphide mapping and structural modelling of the fifth domain of human beta 2-glycoprotein I. AB - Complexes formed by the interaction of negatively charged phospholipids and beta 2-glycoprotein I (beta 2-I) are the target of autoantibodies in systemic lupus erythematosus. The highly positively charged fifth (C-terminal) domain of human beta 2-I was produced as a fusion protein in an Escherichia coli expression system and was shown to bind to the negatively charged phospholipid, cardiolipin, almost as well as the intact protein. In an attempt to define the 3D structure of this domain, the disulphide linkage pattern was determined and shown to be Cys 1 4, Cys 2-5 and Cys 3-6 in contradiction to an earlier report. In the light of this information, the sequence of the fifth domain of beta 2 I (beta 2-I-5) is readily aligned with that of the 16th repeat of factor H, of which the 3D structure is known, and a model of beta 2I-5 has been built by homology. On the basis of the model we suggest residues that might be the target of profitable site-directed mutagenesis in structure-function studies. PMID- 1426289 TI - Segments of Escherichia coli genome similar to the exons of human prothymosin alpha gene. AB - Identification of the putative prothymosin alpha homolog in Escherichia coli cells prompted the search for a prothymosin alpha-coding gene in the E. coli genome. A set of interspersed DNA segments was identified, which match various parts of the human prothymosin alpha molecule. Their location in the E. coli genome and high degree of similarity with the appropriate regions of the human prothymosin alpha gene suggest that some kind of trans-splicing should exist in E. coli, which could be responsible for bringing these putative bacterial prothymosin alpha-coding exons together. PMID- 1426290 TI - Oncogenes and oncoproteins as tumor markers. AB - A major problem in the management of patients with cancer is the lack of specific tumor markers for the early detection, the accurate prediction of biological behavior and for accurate assessment of prognosis. A new and exciting answer to this problem may now become available following the discovery of specific genes associated with malignancy. The role of such genes and their products are now being identified and their role in cancer is under intense investigation. On a clinical level, these genes and their products may allow us to improve our understanding of disease etiology and provide more precise diagnostic, prognostic and therapeutic characterization of individual tumors. This paper discusses the possibilities of using the altered expression of oncogenes and tumor suppressor genes and their products in neoplastic tissues as markers for the diagnosis and prognosis of malignant disease. These data support the view that detailed analysis of such gene expression has the potential to predict a tumor's behavior as well as the response to different treatment modalities. PMID- 1426291 TI - Intra-operative electron beam radiotherapy and abdomino-pelvic surgery for cancer: influence on immunological parameters. AB - Evolution of some immunological parameters was observed during the first month in 20 patients with different abdomino-pelvic cancers who underwent surgery with intra-operative radiation therapy (IORT) (mean dose of 19.44 Gy, range 15, 25). Observed parameters before (DO-) and after procedure (DO+), on seventh (D7) and fourteenth (D14) days and fifth week (D30) were: lymphocyte count, lymphocyte subsets (CD19, CD3, CD4, CD8, CD56), natural killer (NK) activity, immunoglobulins, C3 and C4b fractions of complement, soluble receptor for interleukin 2 (sIL2-R). Results showed a decrease of circulating lymphocytes (DO : 1189 +/- 168 cells/mm3; D7: 889 +/- 91; P = 0.011), of absolute number of CD3 lymphocytes (DO-: 785 +/- 114 cells/mm3; D7: 563 +/- 86; P = 0.025), of CD4 lymphocytes (DO-: 441 +/- 70 cells/mm3; DO+: 299 +/- 43; P = 0.013) and of CD8 lymphocytes (DO-:361 +/- 50 cells/mm3, D7:250 +/- 44; P = 0.006). All values returned towards preoperative levels by D30. Absolute number of NK cells was unchanged but NK activity was significantly diminished (effector target ratio 5:1 DO-:33 +/- 5%; DO+:44 +/- 7%; D7:18 +/- 3%; D14:21 +/- 4%; D30:25 +/- 4%). sIL2-R was significantly enhanced from D7 to D30. All these impairments are moderate and these observations provide some evidence of satisfactory tolerance to IORT for abdomino-pelvic cancers during the immediate postoperative period. PMID- 1426292 TI - Delay in the diagnosis of breast cancer: the effect of the introduction of fine needle aspiration cytology to a breast clinic. AB - Fine needle aspiration cytology (FNAC) was introduced to a District General Hospital Breast Clinic in 1984 and since that time the rate of surgical excision biopsy for benign breast disease has halved. The rate of benign to malignant breast operations fell from 2.0 to 0.7 over a 7-year period from 1982 to 1988. During this period the diagnosis of breast cancer was made at the first clinic appointment in 85% of women. However, a delay in diagnosis of more than 50 days occurred in 33 patients (6.9%) and there was little difference in the annual rate of delayed diagnosis despite the addition of FNAC as an extra diagnostic tool in the later years of the study. Eighty-five per cent of patients with a delayed diagnosis were under the age of 55 (mean and median age 47) years. FNAC is a useful adjunct in the management of patients with diagnostic breast problems, but even in combination with mammography is not always sufficiently sensitive to exclude malignancy, particularly in young women. PMID- 1426293 TI - Surgery for local recurrences following deficient radical mastectomy for breast cancer: a selected series of 39 cases. AB - Thirty-nine patients with locally recurrent cancer, previously treated elsewhere by mastectomy, were considered. At clinical examination, doubts arose as to the efficiency of previously performed mastectomies. Recurrent lesions, in the absence of distant metastases, were nodular, cutaneous or subcutaneous, in the area of previous 'radical mastectomy'. Second surgery consisted of a wide excision together with a surgical revision of axilla. No radiotherapy was administered to the thoracic wall after surgery. Adjuvant chemotherapy (CMF) was given to 26 node-positive women. Median follow-up was 48 months. Pathological reports showed that portions of mammary gland and axillary lymph nodes had been left behind by primary surgery in 29 and 34 cases, respectively. In 26 cases lymph nodes were metastatically involved. Local control has been maintained in 32 patients, 21 of whom are alive and free of disease. PMID- 1426294 TI - Stage I cutaneous malignant melanoma: risk factors of loco-regional recurrence after wide local excision and clinical perspectives. AB - Two hundred and nineteen patients admitted to the Centre Claudius Regaud over a 14-year period for a stage I cutaneous malignant melanoma were retrospectively evaluated for loco-regional recurrence rates, risk factors and survival rates following wide primary excision. Five and 8 year survival rates corrected for deaths owing to concurrent illness were 77% and 73%. The loco-regional control rate was 69% (151/219). Distant metastases occurred in 59% (40/68) of patients who had a loco-regional recurrence, versus 11% (16/151) of patients when loco regional control was obtained (P < 0.001). Multivariate analysis was used to ascertain which risk factors act independently as predictors of poor loco regional control. Anatomical location of the primary ('head and neck-trunk-hands and feet' vs 'proximal limb') and thickness formed the best model in this respect among 11 prognostic factors studied. Since loco-regional recurrence may be associated with an increased risk of distant metastatic disease, we advocate the use of elective regional lymph node dissection in stage I patients at high risk of loco-regional recurrence in the hope that a portion of these patients may have increased survival owing to lack of development of widespread metastases. PMID- 1426295 TI - Is preoperative transrectal ultrasonography of value in localised prostatic carcinoma? A blind comparative study between preoperative transrectal ultrasonography and the histopathological radical prostatectomy specimen. AB - Digital rectal examination (DRE) for staging is subjective and unreliable. Understaging has been reported in 25-72% and clinical overstaging of T3 tumors varies from 24-50%. In the present study of 15 patients, transrectal ultrasound (TRUS) staging was compared, in a blind comparative fashion, with pathological staging of the surgical specimen. Multifocal lesions were present in 8/15 patients (53%). A distinction was made between capsular involvement and 'clear' capsular penetration. TRUS was more sensitive in predicting capsular involvement than DRE (83% vs 17%), but the specificity was low (67% vs 100%). If capsular perforation was considered, the sensitivity and specificity of TRUS are 43% and 91%, respectively. Sensitivity and specificity for seminal vesicle tumor involvement by TRUS was 63% and 86%. Using TRUS the overall staging was improved by 33% compared with DRE and therefore TRUS is considered to be a valuable acquisition in localising and staging prostate cancer. PMID- 1426296 TI - Radical prostatectomy for localized prostate cancer. AB - A retrospective analysis of 70 patients, undergoing a radical prostatectomy in 1989 and 1990 is reported. The value of computed tomography (CT) scanning in preoperative lymph node staging should be reconsidered. Evaluation of the resection margins is of utmost importance as is the distinction between capsular invasion, penetration and transgression. The etiology of local failure and its treatment are discussed. PMID- 1426297 TI - Malignant thyroid tumours 1932 to 1972: the outcome in 492 patients. AB - We report on 492 patients treated for thyroid cancer at the Royal Marsden Hospital between 1932 and 1972: 380 of the patients are now dead. Eighty-three per cent (n = 410) are tumours of follicular cell origin. We found the crude 20 year probability of survival to be 54% in papillary carcinoma, 29% in follicular carcinoma and 1% in anaplastic carcinoma. Considering solely cancer deaths, the survival in papillary cases was 68%. Age, histology (tumour type), extent of primary tumour (T stage), haematogenous metastases (M1 stage) and, to a lesser extent, sex exercised a significant influence on survival. We support the use of these five factors to produce a prognostic index for estimating the level of risk for tumours of follicular cell origin. We add our experience in the non follicular cell tumours of medullary carcinoma (3%), lymphoma (7%) and fibrosarcoma (1%). PMID- 1426298 TI - Retroperitoneal sarcoma in a series of 51 adults. AB - Fifty-one patients with retroperitoneal sarcoma underwent surgery at the University Clinics of Hamburg from 1970 to 1988. Malignant schwannoma, liposarcoma and malignant fibrous histiocytoma were the most common histological types. High grade sarcomas (G3) predominated (42%), while 26% were graded G2 and 33% G1. Complete resection was possible in 59% of cases. Reoperation for local recurrence and debulking in case of not completely resectable disease was common. Regional lymph node metastasis was found in 20% of cases. The peritoneum was the preferred location of metastatic spread. All adjuvant chemotherapies were followed by tumour recurrences. After adjuvant radiotherapy three of six patients remained free of disease. In cases of residual tumour we observed few partial responses on chemo- and radiotherapy, and all patients died because of the disease. The mean survival time was 60 months, the 5- and 10-year survival rates were 35% and 15%, respectively. Factors influencing prognosis in univariate analysis included grade, size, resectability, presence of metastatic spread, histological type, microscopic local growth (infiltrative vs intact pseudocapsule of fibrous tissue) and local recurrence. With multivariate analysis grade, size and lymph node metastasis retained their prognostic significance. PMID- 1426299 TI - How long is a 6 cm margin of resection in the stomach? AB - In order to assess whether the gastric wall undergoes some change in length during gastrectomy operation for cancer, we measured the variation in length of the anterior gastric wall in 25 patients. The first measurement was made at the beginning of laparotomy by placing two stitches on the anterior gastric wall and registering the distance between them. A second and a third measurement were recorded when the stomach was fully isolated just before its transection and subsequently on the anatomic table. The results indicate that the usual recommendations made by pathologists to maintain a 6 cm margin of tissue clearance proximally to the cephalic edge of the tumour, can be safely followed by the surgeons who can correctly assess, during operation, the distance between tumour and the desirable line of transection since no misleading reduction in size of the resected specimen takes place. PMID- 1426300 TI - Saphenous vein grafts for anatomical variations encountered at surgical insertion of a hepatic artery catheter. AB - Fifty-five consecutive patients, with colorectal metastases confined to the liver, underwent surgical placement of a hepatic artery catheter. At angiography, abnormal hepatic arterial anatomy was present in 33% of patients. In the majority of patients, the hepatic artery catheter was inserted in the conventional manner. In eleven patients with unusual arterial anatomy, a saphenous vein graft was used to create a conduit for the catheter. Satisfactory perfusion was obtained in all patients. PMID- 1426301 TI - Prognosis of surgically treated radiation-induced damage to the intestine. AB - A series of 88 patients operated on during 24 years for radiation-induced damage (RID) to the intestinal tract were retrospectively reviewed and clinical and surgical factors were related to the ultimate prognosis by multivariate analysis. The first operation was performed on the small intestine in 47 patients, the large intestine in 32 patients or both in nine patients. Postoperative complications occurred in 35 patients (40%), with fatal outcome in 12 (13%). Thirty-one patients (35%) required further surgery and altogether 19 patients (22%) ultimately died from RID. Negative prognostic factors after the first operation were postoperative intestinal leak (P < 0.05) and operation for fistula or perforation (P < 0.01). The outcome after the last operation was negatively influenced by intestinal leak (P < 0.001) by the choice of bypass as operative procedure (P < 0.01) and by operation for fistula or perforation (P < 0.01). In addition, 43% of the patients in whom the disease had progressed between two explorations died from RID. Thus, the severity of the RID as diagnosed at laparotomy, and progression of the disease between two subsequent explorations were related to the prognosis. Care should be taken to avoid intestinal leak. Resections should be preferred to bypass of injured intestine whenever possible. PMID- 1426302 TI - Carcinoma of the pancreas and papilla of Vater--assessment of resectability and factors influencing resectability in stage I carcinomas. A prospective multicentre trial in 472 patients. AB - Between 1984 and 1987, 472 patients with histologically or cytologically verified carcinomas of the pancreas or papilla of Vater, were accrued in the Norwegian Pancreatic Cancer Trial. Surgical assessment revealed resectability in 29% (94 of 330) of the pancreatic tumours and 89% (25 of 28) of the papillar tumours. Tumours of the pancreatic head were resectable in 32% (84 of 259). The sensitivities of the different diagnostic methods in patients with resectable tumours were: FNAC (fine needle aspiration cytology) 80%, ERCP (endoscopic retrograde cholangio-pancreatography) 78%, PTC (percutaneous transhepatic cholangiography) 73%, ERCP with duct cytology 67%, CT (computed tomography) 58%, US (ultrasound) 42% and angiography 22%. The positive predictive values (PV+) in resectable disease were: US 29%, CT 35%, ERCP 43% and angiography 44%. Corresponding figures for unresectable disease were US 95%, CT 97%, ERCP 75% and angiography 88%. Resectable tumours of the pancreas and papilla of Vater had an average macroscopic diameter of 3.2 x 3.4 cm and 2.2 x 2.3 cm, respectively. Tumour size increased with stage. Increasing tumour size and abdominal pain combined with short diagnostic delay both decreased resectability rate, whereas a combination of long diagnostic delay and abdominal pain had a more favorable resectability rate. Radical pancreatic surgery, if effective in the treatment of carcinoma of the pancreas or papilla of Vater, should not be undertaken if any preoperative diagnostic test demonstrates signs of indisputable unresectability. Available methods for the evaluation of resectability in patients lacking such signs are insufficient. This necessitates exploratory laparotomy in many patients. PMID- 1426303 TI - The prognostic value of the tumour markers CA 195 and CEA in patients with adenocarcinoma of the pancreas. AB - The serum levels of CA 195 were determined in 52 patients with histologically proven pancreatic carcinoma and compared with carcino-embryonic antigen (CEA), serum bilirubin and albumin. CA 195 levels were raised above the upper limit of 20 U/ml in 42 cases, giving a sensitivity of 80% for the detection of pancreatic carcinoma, whereas CEA was raised in only 55%. The levels of CA 195 and CEA were significantly higher in patients with metastatic disease, but potentially curable cases were not discriminated. Bilirubin and albumin levels were not significantly related to either the presence of metastases or the levels of the tumour markers. At the time of initial presentation, levels of both tumour markers correlated with the eventual duration of survival, but bilirubin and albumin did not. Significant increases in CEA and CA 195 were found in sequential blood samples, as the disease progressed. Neither CA 195 nor CEA was of sufficient sensitivity to be of value for screening, but both give an indication of the presence of metastases and of the subsequent duration of survival. CA 195 appeared to be more sensitive and might help to assess progress of the disease. PMID- 1426304 TI - Primary lymphoma of the trachea. PMID- 1426305 TI - Spontaneous remission of bladder neoplasm. AB - A case of spontaneous remission of bladder cancer in an 85-year-old man is reported. The clinicopathological features are presented and the literature reviewed. PMID- 1426306 TI - Puberty and polycystic ovarian syndrome: the insulin/insulin-like growth factor I hypothesis. AB - OBJECTIVES: To provide an up-to-date review of studies that have examined the physiological effects of insulin and insulin-like growth factor I (IGF-I) on ovarian growth, maturation, and steroid synthesis, their physiological role in puberty, and their pathophysiological role in polycystic ovarian syndrome (PCOS). To deduce from these data a hypothesis, explaining the pathogenetic connections between puberty and PCOS. DATA IDENTIFICATION: The most relevant studies related to this topic have been identified through a computerized bibliographic search (MEDLINE) and through manual scanning of what has been published during recent years in the most important journals in the field of reproductive endocrinology. RESULTS: Insulin and IGF-I stimulate ovarian growth and potentiate the actions of gonadotropins on ovarian steroid synthesis. Insulin also augments the bioactive concentrations of IGF-I and androgens through regulation of the synthesis of their respective binding proteins insulin-like growth factor-1 binding protein (IGFBP-1) and sex hormone-binding globulin (SHBG) in the liver. Insulin and IGF-I might also be able to increase the adrenal sensitivity to adrenocorticotropic hormone (ACTH). Insulin resistance with compensating hyperinsulinism is a common feature of PCOS. It is also a normal phenomenon during puberty. Polycystic ovarian syndrome often develops during puberty. Ultrasonographic investigations suggest that it is much more common during adolescence than generally assumed. Actually, there is a striking resemblance between the endocrine characteristics of puberty and some forms of PCOS. Both conditions are characterized by insulin resistance, hyperpulsatile gonadotropin secretion, hyperactive ovarian and adrenal androgen synthesis, and decreased levels of IGFBP-1 and SHBG. CONCLUSION: We propose the progressively increasing insulin levels and IGF-I activity during puberty as inducing factors in the development of PCOS in susceptible subjects. PMID- 1426307 TI - The intrauterine device, pelvic inflammatory disease, and infertility: the confusion between hypothesis and knowledge. PMID- 1426308 TI - Ovulation induction in women age 40 and older: the importance of basal follicle stimulating hormone level and chronological age. AB - OBJECTIVES: To determine pregnancy and livebirth rates for women age 40 and older undergoing ovulation induction and to assess the impact of basal follicle stimulating hormone (FSH) on outcome in these patients. DESIGN: Prospective, observational. SETTING: Fertility service of university medical center. PATIENTS: Infertile couples in whom the female partner was age 40 or older referred for ovulation induction therapy. INTERVENTION: Assessment of basal hormonal status; ovulation induction. MAIN OUTCOME MEASURES: Clinical pregnancy rate (PR), livebirth rate. RESULTS: Analysis of 402 cycles in 85 women age 40 and older demonstrated a clinical PR of 3.5% per cycle (95% confidence interval [CI] 1.7% to 5.3%). The livebirth rate was 1.2% per cycle (95% CI 0.1% to 2.3%). Women with a basal FSH < 25 IU/L and age < 44 years had a clinical PR of 5.2% per cycle (95% CI 2.5% to 7.9%) compared with 0.0% per cycle (95% CI 0.0% to 2.1%) in cases in which either basal FSH was > or = 25 IU/L or age was > or = 44 (P < 0.005). The prognostic importance of basal FSH and chronological age was confirmed by multivariate logistic regression analysis. The predictive value of the resulting regression equation was high (R2 = 0.94; P < 0.01). CONCLUSIONS: Pregnancy and livebirth rates are generally low during ovulation induction in women age 40 and older. In combination, basal FSH and chronological age are accurate predictors of PR, in these couples and can define a subset of patients with a more favorable prognosis. The spontaneous abortion rate in women who do conceive is high, substantially lowering the livebirth rate. PMID- 1426309 TI - Suppression of ovarian function with the transdermally given synthetic progestin ST 1435. AB - OBJECTIVE: To study transdermal administration of the synthetic progestin ST 1435 and effectiveness of the steroid in suppression of ovarian function. DESIGN, PATIENTS: The effect of transdermal administration of the synthetic progestin ST 1435 in suppression of ovarian function was studied in a short term (17 to 93 days) study in healthy regularly menstruating women. SETTING: The outpatient clinic of the City Maternity Hospital, Helsinki, Finland. INTERVENTION: Nine women used the progestin ST 1435 transdermally during a total of 21 menstrual cycles. Treatment was started on the 5th day of the menstrual cycle and continued for 17 to 93 days. Three different daily doses (0.5, 0.8, and 1.0 mg) were tested. The steroid was applied to the periumbical area once a day in a gel. MAIN OUTCOME MEASURES: Serum concentrations of ST 1435, progesterone, and estradiol (E2) were determined during the luteal phase of control cycles and in a total of 16 treatment cycles. Bleeding records were kept and side effects registered. RESULTS: Transdermal absorption of the progestin ST 1435 resulted in relatively constant serum concentrations in each subject, depending on the dose used. All doses caused changes in ovarian function. With the 0.5-mg/d dose, inhibition of ovulation was observed in three of five treatment periods. The 0.8-mg/d dose was high enough to inhibit ovulation in 7 of 10 cycles analyzed. With the 1.0-mg/d dose, the serum concentrations of the progestin were high, and anovulation was seen. Serum E2 concentrations were variable in all cases; occasional high peak values were seen, typical of progestin treatment. Bleeding control was variable; irregular bleeding was seen, especially in anovulatory cases. CONCLUSIONS: A 0.8 mg dose of the progestin ST 1435 administered transdermally once a day appeared to suppress ovulation, if properly applied, and excessive suppression of ovarian function was not seen. The steroid was well accepted. The synthetic progestin ST 1435 given transdermally represents an effective alternative for inhibition of ovulation and for progestin therapy. PMID- 1426310 TI - Daily levels of salivary progesterone during menstrual cycle in adolescent girls. AB - OBJECTIVE: To study the daily levels of salivary progesterone (P) during the menstrual cycles of adolescent girls 14 to 19 years of age and the occurrence of anovulations and defective luteal phases. DESIGN: The salivary P levels were analyzed by radioimmunoassay from three age groups of girls (n = 65) and compared with groups of 20 to 25 years (n = 14) and 25 to 43 years old women (controls, n = 19). One cycle per subject was used in the analyses. PARTICIPANTS: The randomly selected healthy schoolgirls were divided into three groups according to their postmenarcheal years: 1 to 2, 3 to 4, and 5 to 6 years (n = 15, 29, and 21, respectively). RESULTS: The youngest group had longer cycles and follicular phases than the older ones, but their mean luteal phase parameters did not differ. Interestingly, signs of temporary derangement of corpus luteum (CL) function (e.g., suppressed P secretion parameters) were observed in the group of 3 to 4 years. In the young adults (20 to 25 years old), the mean P secretion parameters did not differ significantly from the controls. There were more anovulatory cycles in the adolescent groups (25% to 33%) and in young adults (29%) than in controls (0%). CONCLUSION: About one third of the cycles are anovulatory from the age of 14 and 15 up to 20 to 25 years. In contrast to earlier findings, CL usually functions fully even in the first ovulatory cycles. Transient disturbances in luteal phase P secretion are most common 3 to 4 years after menarche. PMID- 1426311 TI - The role of blocking factors and antipaternal lymphocytotoxic antibodies in the success of pregnancy in patients with recurrent spontaneous abortion. AB - OBJECTIVE: To elucidate the role of mixed lymphocyte reaction blocking factors (BF) and complement-dependent antipaternal lymphocytotoxic antibodies on the outcome of pregnancy in unexplained recurrent spontaneous aborters. DESIGN: A controlled study of immunotherapy in which the treated group was immunized with the husband's or a third party donor's lymphocytes and the control group received autologous lymphocytes. SETTING: Tertiary care institution. PATIENTS: Forty-three patients in the control group and 48 patients in the treated group. INTERVENTION: The before and after immunization levels of BF and antipaternal lymphocytotoxic antibodies were measured. MAIN OUTCOME MEASURES: The existence or changing pattern of BF and antipaternal lymphocytotoxic antibodies levels before and after immunization had no influence on the pregnancy outcome in either group of patients. CONCLUSION: Neither BF nor antipaternal lymphocytotoxic antibodies is essential for successful pregnancy. They probably reflect the immunological response of the mother to exposure to fetal antigens. PMID- 1426312 TI - Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries. AB - OBJECTIVE: To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. DESIGN: Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). SETTING: Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. PATIENTS: Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. MAIN OUTCOME MEASURES: Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. RESULTS: The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. CONCLUSIONS: The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD. PMID- 1426313 TI - A unique point mutation in the androgen receptor gene in a family with complete androgen insensitivity syndrome. AB - OBJECTIVE: To further delineate the diversity of genetic alterations in the gene coding for the androgen receptor in individuals with the androgen insensitivity syndrome and to increase our understanding of the disease at the molecular level. DESIGN: This was a prospective study in which genomic deoxyribonucleic acid (DNA) from individuals with androgen insensitivity were examined through the polymerase chain reaction and DNA sequencing analysis. PATIENTS: Eleven complete and four individuals with partial androgen insensitivity syndrome were examined. RESULTS: Exons two through eight were grossly intact in all study subjects. Nucleotide sequence analysis revealed that three of three related family members with complete androgen insensitivity had the same guanine to adenine base substitution in exon five of the steroid-binding domain. CONCLUSION: The subsequent alanine to threonine amino acid conversion may have resulted in a configurational change of the androgen receptor protein leading to complete androgen insensitivity. This precise alteration has not been previously identified in the human androgen receptor gene in patients with the androgen insensitivity syndrome. PMID- 1426314 TI - Cutaneous application of an androstenedione gel as an in vivo test of 5 alpha reductase activity in women. AB - OBJECTIVE: Assessment of an in vivo test for 5 alpha-reductase activity using serum markers, 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide, after the cutaneous application of androstenedione (A). DESIGN: An A gel was applied for 6 days to the skin of normal women, male volunteers, and hirsute and nonhirsute patients with polycystic ovarian syndrome (PCOS). Blood samples were obtained at baseline and on day 6 of the A gel application. Blood samples were assayed for A, 5 alpha-androstane-3 alpha,17 beta diol glucuronide, and androsterone glucuronide. In three hirsute women, the protocol was followed before and after receiving an oral contraceptive (OC) and spironolactone 200 mg/d for 3 months. SETTING: The study was performed in the outpatient clinic of the Division of Reproductive Endocrinology and Infertility, Women's Hospital of the Los Angeles County and University of Southern California Medical Center in Los Angeles, California. PATIENTS, PARTICIPANTS: A total of eight nonhirsute patients with PCOS, seven hirsute patients with PCOS, and six male volunteers were enrolled in the study. Five normal women served as a control group. MAIN OUTCOME MEASURE: Serum A increased after 6 days by a similar magnitude in all groups. Serum androsterone glucuronide showed a significant increase from baseline only in the hirsute group (P < 0.03), whereas the increase in 5 alpha-androstane-3 alpha,17 beta-diol glucuronide was not statistically significant. RESULTS: The ratio of the increases in serum androsterone glucuronide over serum A was significantly higher in the hirsute group (P < 0.02). In the three hirsute patients who were placed on an OC and spironolactone, serum 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide decreased after 3 months and did not increase with application of the gel for another 6 days. CONCLUSION: The cutaneous application of A provides a useful assessment of in vivo 5 alpha-reductase activity. However, because we found that A absorption varied considerably (30% to 62%), we suggest that this in vivo test may not provide more information than baseline determinations of 5 alpha-androstane-3 alpha,17 beta-diol glucuronide and androsterone glucuronide. It may, however, be useful as a parameter for assessing the effectiveness of various treatment regimens for hirsutism. PMID- 1426315 TI - 11 beta-hydroxyandrostenedione in plasma, follicular fluid, and granulosa cells of women with normal and polycystic ovaries. AB - OBJECTIVE: To investigate the role of 11 beta-hydroxylase/11 beta hydroxyandrostenedione (11-OHA) in the ovarian metabolism of androgens in women with polycystic ovaries (PCO) and its associated syndrome (PCOS). DESIGN: Prospective observational study examining the plasma and follicular fluid (FF) concentrations of 11-OHA, testosterone (T), androstenedione (A), and cortisol from women with PCOS and normal women in spontaneous and stimulated cycles. SETTING: The study was carried out in an infertility department and an endocrine research laboratory of a university hospital. PATIENTS: Five groups of women were studied. Blood was taken from 53 women with PCOS and 13 normal controls. Follicular fluid and blood was obtained from 51 women with stimulated cycles undergoing in vitro fertilization embryo-transfer (IVF-ET), 27 of whom had PCO and 24 had normal ovaries. Follicular fluid alone was also taken from 13 women with normal ovaries undergoing laparoscopies. INTERVENTIONS: Clear FF was obtained for analysis during oocyte collection. Granulosa cells (GCs) were obtained from seven women with PCO undergoing IVF-ET and were incubated with radiolabeled substrates. RESULTS: Circulating concentrations of T and 11-OHA were higher in women with PCOS compared with women with normal ovaries. In women with PCO receiving exogenous gonadotropin, only 11-OHA concentrations were higher. Concentrations of all steroids measured were higher in FF than plasma, with plasma 11-OHA concentrations 4 to 12 times higher in FF. Significantly lower concentrations of 11-OHA were found in the FF of women with PCO compared with women with normal ovaries. There was no evidence of 11 beta-hydroxylation of A by GCs. CONCLUSIONS: Although the raised plasma concentrations of 11-OHA may reflect hyperandrogenism in PCOS and lower 11-OHA concentrations in FF in women with PCO suggest abnormal androgen metabolism, neither can be regarded as a marker for this syndrome. PMID- 1426316 TI - Interleukin-1: local production and modulation of human granulosa luteal cells steroidogenesis. AB - OBJECTIVES: To investigate the possibility of local interleukin-1 (IL-1) and IL-1 inhibitor production by human granulosa and cumulus cells and to assess their direct effects on the steroidogenesis of these cells in vitro. DESIGN: Prospective study. PARTICIPANTS: Normal ovulatory women undergoing ovulation induction for in vitro fertilization. INTERVENTION: Pretreatment of patients with gonadotropin-releasing hormone analogue, human menopausal gonadotropin, and human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURES: Retrieval and isolation of granulosa luteal cells and follicular fluid (FF). Granulosa luteal cells and cumulus cells cultured and analyzed by fluorescent activated cell sorter. Follicular fluid separated and bioassayed for IL-1 and IL-1 inhibitory activity. Steroid measurement performed. Interleukin-1 inhibitor purified. Interleukin-1 and IL-1 inhibitor bioassay performed. Statistical analysis made and interpreted. RESULTS: Interleukin-1, but not IL-1 specific inhibitory activity, was found in granulosa and cumulus cell cultures and also in FF, only after its purification on a high-pressure liquid chromatography column. Under nonstimulated conditions, neither IL-1 nor IL-1 inhibitor had any effect on basal progesterone (P) or estradiol (E2) secretion. However, IL-1 inhibitor demonstrated significant (P < 0.01) inhibition of hCG-stimulated P secretion (from 200 to 110 ng/10,000 cells per 24 hours). In addition, IL-1 demonstrated a significant (P < 0.05) and dose dependent inhibition of hCG-stimulated E2 production (from 6,832 +/- 460 to 4,237 +/- 141 pg/10,000 cells per 24 hours). CONCLUSIONS: Interleukin-1 may exert a significant local autocrine regulatory role in the human ovary. PMID- 1426317 TI - Effect of growth hormone administration on human ovarian function and steroidogenic gene expression in granulosa-luteal cells. AB - OBJECTIVE: To study the effect of growth hormone (GH) in combination with an ultrashort-term gonadotropin-releasing hormone analogue/human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) regimen in ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized placebo-controlled study. SETTING: University-based IVF program. PATIENTS: Fifty four normally cycling women (27 control and 27 GH-treated) participated in this study. INTERVENTIONS: Human recombinant GH (24 IU)/placebo was given intramuscularly on alternate days starting on cycle day 4 until the day of last hMG injection. RESULTS: Serum estradiol (E2) and progesterone (P) concentrations were slightly lower in the GH group than in the placebo group on the day of hCG injection and 1 day thereafter (P < 0.01 to 0.001). Serum luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone (T), and sex hormone binding globulin did not differ between the groups. The follicular fluid (FF) concentration of T was higher in the GH group than in the placebo group (15.9 +/- 6.0 nmol/L versus 10.2 +/- 4.9 nmol/L, P < 0.005), and no differences were observed in the FF concentrations of E2, P, and insulin-like growth factor I between the groups. In granulosa cells isolated from patients who received GH treatment, the levels of 3 beta-hydroxysteroid dehydrogenase and aromatase messenger ribonucleic acid were significantly higher than in the patients receiving placebo. The number of hMG ampules needed for follicular development and the number of follicles and oocytes recovered were similar in both groups. CONCLUSIONS: These results indicate that GH administration modifies ovarian steroidogenic response to gonadotropins in IVF patients, suggesting a role for GH in the regulation of human ovarian function. PMID- 1426319 TI - The effects of spontaneous luteinizing hormone surges on superovulatory cycles. AB - OBJECTIVE: To determine the effect of a spontaneous luteinizing hormone (LH) surge on the cycle fecundity during superovulation induction. DESIGN: Superovulatory cycles of patients with various diagnoses are retrospectively compared. SETTING: Reproductive Endocrinology Outpatient Clinic. PATIENTS: A total of 1,185 superovulatory cycles from July 1, 1982 until November 1, 1991 are compared. MAIN OUTCOME MEASURE: The probability of achieving a pregnancy per treatment cycle. RESULTS: Patients with unexplained infertility and hyperprolactinemia were more likely to have a spontaneous LH surge during superovulation than patients with either endometriosis or polycystic ovarian disease. However, the cycle fecundity rate did not differ whether or not an LH surge occurred, regardless of the diagnosis. CONCLUSIONS: Spontaneous onset of an LH surge during superovulation induction does not influence the chances for pregnancy. PMID- 1426318 TI - Ovarian steroids modulate human monocyte tumor necrosis factor alpha messenger ribonucleic acid levels in cultured human peripheral monocytes. AB - OBJECTIVE: To determine whether tumor necrosis factor alpha (TNF-alpha) messenger ribonucleic acid (mRNA) levels in human peripheral monocytes are regulated by ovarian steroids. DESIGN: Human granulosa-luteal cells and cultured, activated human peripheral monocytes were subjected to Northern blot analysis for TNF-alpha mRNA. SETTING: Academic research laboratory. PATIENTS: Two human female volunteers of reproductive age and in the luteal phase of the menstrual cycle. RESULTS: Human granulosa-luteal cells produce TNF-alpha mRNA. Physiological levels of progesterone (P) and estradiol (E2) modulate TNF-alpha mRNA from peripheral blood monocytes with an apparent inverse relationship between steroid concentration and TNF-alpha message. CONCLUSIONS: Progesterone and E2 at physiological concentrations regulate TNF-alpha mRNA production. The P antagonist mifepristone (RU486) and the E2 agonist/antagonist tamoxifen modulate total TNF alpha mRNA levels, suggesting involvement of specific receptors. PMID- 1426320 TI - A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization. AB - OBJECTIVE: To compare the effects of gonadotropin-releasing hormone agonist (GnRH a) initiation either preceding or concurrent with controlled ovarian hyperstimulation (COH) in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Fifty-five patients were prospectively randomized to receive either GnRH-a on cycle day 21 before COH until ovarian suppression was achieved (group I) or GnRH-a concurrently with COH commencing on cycle day 3 (group II). MAIN OUTCOME MEASURES: Serum gonadotropin and ovarian steroid hormone levels, as well as fertilization, spontaneous abortion, and live birth rates. RESULTS: Twenty-six patients in group I and 29 patients in group II underwent COH for IVF-ET. Patients in group II had significantly higher serum luteinizing hormone, progesterone, and testosterone levels during stimulation with human menopausal gonadotropins (hMG) before oocyte retrieval (P < 0.05). Despite similar fertilization, biochemical, and clinical pregnancy rates, the spontaneous abortion rate was higher in group II (5/6) compared with group I (1/7) (P < 0.05). Thus, the live birth rate/retrieval for group I was 6 of 24 (25%) as compared with that of group II, which was 1 of 26 (3.8%) (P < 0.05). CONCLUSIONS: The initiation of GnRH-a in the follicular phase concurrently with hMG is associated with evidence of premature luteinization, hyperandrogenemia, and poorer pregnancy outcome compared with luteal phase administration of GnRH-a before hMG for IVF-ET. PMID- 1426321 TI - Nuclear degeneration and meiotic aberrations observed in human oocytes matured in vitro: analysis by light microscopy. AB - OBJECTIVE: To apply an improved air-dry procedure for the light microscopic identification of both degenerate and aberrant meiotic configurations in cultured human oocytes. MATERIAL AND DESIGN: Meiotically immature, normal appearing human oocytes retrieved after oophorectomy were placed into culture for 9 to 46 hours. Subsequently, oocytes were assessed morphologically and then air dried for light microscopic examination of chromatin configurations. MAIN OUTCOME MEASURES: Oocyte chromatin configurations were identified as normal, degenerate, or aberrant and then classified according to meiotic stage. Retrospective analyses were conducted to determine if [1] normal meiotic configurations were associated with morphologically viable oocytes and [2] degenerate or aberrant meiotic configurations were always associated with degenerate oocytes. In addition, for each meiotic stage, the proportion of oocytes exhibiting either degenerate or aberrant chromatin configurations was calculated. RESULTS: Of 101 oocyte chromatin configurations analyzed, 71.3% were normal, 11.9% were degenerate, and 16.8% displayed meiotic aberrations. Retrospective analyses revealed that the majority of both normal and aberrant chromatin configurations were associated with morphologically viable oocytes (93.1% and 88.2%, respectively), whereas all of the degenerate chromatin configurations were associated with morphologically degenerate oocytes. When assessed by stage, nuclear degeneration was observed exclusively at the germinal vesicle and diakinesis stages, whereas meiotic aberrations occurred most frequently after chromosome condensation. These aberrations were manifested either as clumped metaphase I configurations or as two distinct groups of bivalents that appeared to result from bivalent migration along the meiotic spindle without homologue segregation. CONCLUSIONS: Slightly > 25% of human oocytes recovered after oophorectomy were incapable of undergoing normal meiotic maturation in culture. The majority of these abnormal oocytes appeared morphologically normal and yet possessed meiotic aberrations. These observations indicate that caution should be taken when using oocytes matured in vitro for application in assisted reproductive technology programs. PMID- 1426322 TI - Effects of varicocele treatment in adolescents: a randomized study. AB - OBJECTIVE: To study the effects of varicocele treatment on testicular function in adolescents. DESIGN: A prospective controlled study in 88 randomly selected adolescents. SETTING: All participants were referred to the fertility outpatient clinic of our university hospital. PARTICIPANTS: All participants with a varicocele were randomly assigned into two groups. Group 1 (n = 33) was not treated, whereas group 2 (n = 34) was treated. A similar group of healthy volunteers without a varicocele served as a control group (group 3, n = 21). INTERVENTIONS: Testes volumes were measured at intake and during follow-up using an orchiometer. Semen analysis was performed according to standard procedures both at intake and after 1 year of follow-up. Serum hormone levels were determined at intake using a radioimmunoassay. Treatment was performed by means of transcatheter embolization of the left testicular vein. MAIN OUTCOME MEASURES: Testes volumes and semen quality at intake and after 1 year of follow-up were compared within and between the three groups. Hormonal parameters were determined at intake only. RESULTS: Before treatment, the mean left testis volume in groups 1 (n = 26) and 2 (n = 27) (20.0 mL; 95% confidence interval [CI]: 18.2 to 21.8 and 21.6 mL; 95% CI: 19.4 to 23.8, respectively) were significantly smaller than those in the control group (n = 19) (24.5 mL; 95% CI: 22.7 to 26.4). During follow-up, left testis volumes of the treated group were comparable with those in the control group (24.2 mL; 95% CI: 22.2 to 26.1 and 24.8 mL; 95% CI: 23.0 to 26.7 respectively) and significantly (P < 0.001) different from the untreated group (20.3 mL; 95% CI: 18.8 to 21.8). A significant increase in left (P < 0.01) as well as right (P < 0.05) testis volume was observed after treatment. Semen parameters before treatment were not significantly different between the three groups. Sperm concentration increased significantly (P < 0.01) from 47.4 x 10(6)/mL (95% CI: 42.5 to 53.3) to 68.9 x 10(6)/mL (95% CI: 50.6 to 87.2) in the treated group, whereas semen quality in the untreated and control groups did not change. Although both testes volumes and sperm concentration improved in the treated group, these phenomena were not consistently correlated to each other. CONCLUSIONS: Although not apparent in all adolescents, varicocele correction resulted in an increase in left testis volume and sperm concentration. At this moment, it is not clear if early preventive treatment of varicocele in adolescents, in time, will have a positive effect on testicular function. PMID- 1426323 TI - Accuracy and precision of the CellForm-Human automated sperm morphometry instrument. AB - OBJECTIVE: To evaluate the accuracy and precision of the CellForm-Human (CFH) automated sperm morphometry instrument (Motion Analysis Corp., Santa Rosa, CA). SETTING: Clinical and research andrology and in vitro fertilization laboratories. PATIENTS: Individuals undergoing semen evaluation and infertility work-up. RESULTS: Coefficients of variation for repeated measures of the same sperm were 1%. Coefficients of variation of normal sperm measurements were 7.4% to 12.8%, depending on the measure. Of the objects recognized as sperm by the instrument, 6.8% were debris; hence, the sperm recognition algorithms need improvement. Mean values for all CFH measures of normal sperm from specimens clinically classified as having predominantly normal, tapered, or amorphous sperm were not different; hence, the morphometry of normal sperm from normal specimens was similar to normal sperm from specimens with two different abnormalities. The instrument classified sperm as abnormal if their length or width fell outside a critical range of values recommended by the World Health Organization. Using this method, manual and CFH classification agreed unambiguously 60% of the time. When disagreement occurred, length or width marginally exceeded the range by no more than 0.1 microns. In these cases, the technician classified sperm as normal 25% of the time and classified them as abnormal 6% of the time. Because this disagreement between methods is well below the resolution of manual methods, the overall accuracy of CFH was 91% for cell type classification. CONCLUSION: At its present stage of development, the CFH instrument exceeds the accuracy and precision of most manual approaches. With improvements in sperm recognition and type classification algorithms, it could significantly improve the reliability of morphology assays in clinical and research laboratories. PMID- 1426324 TI - Poor in vitro fertilization outcome with semen yielding low sperm density "swim ups" is not because of altered sperm motion parameters. AB - OBJECTIVE: To examine fertilization, cleavage, and pregnancy rates (PRs) with semen samples yielding numbers of total motile sperm per swim-up ranging from < 1 to > 20 x 10(6) and to correlate the findings with changes, if any, in the sperm motion parameters. DESIGN: Fertilization, cleavage, and pregnancy outcomes in 439 in vitro fertilization (IVF) cycles were correlated with the total number of motile sperm per swim-up and the sperm motion parameters as determined with an automated semen analyzer. SETTING: A university-based tertiary referral hospital center. PATIENTS: Patients undergoing IVF or intrauterine insemination treatments for multiple etiologies. RESULTS: Higher numbers of motile sperm per swim-up, most notably above the value of 3 x 10(6) motile sperm, were associated with improved fertilization rates and viable PRs. Sperm velocity, linearity, amplitude of lateral head displacement, and flagellar beat per cross frequency for sperm from swim-ups with poor or good pregnancy outcome, however, showed no significant differences. CONCLUSIONS: As a group, semen samples that yield < or = 3 x 10(6) motile sperm per swim-up are associated with poor fertilization rates, cleavage rates, and PRs. This relationship can not be attributed to differences in sperm motion parameters. PMID- 1426325 TI - The culture of human epididymal epithelium and in vitro maturation of epididymal spermatozoa. AB - OBJECTIVE: To promote human sperm maturation in vitro. DESIGN: Spermatozoa from the proximal epididymis were coincubated with epididymal epithelial fragments. SETTING: Hospital and research institute. PATIENTS, PARTICIPANTS: Tissue samples were obtained from men undergoing epididymovasostomy procedures or vasectomy. INTERVENTIONS: Fragments of epididymal epithelium formed everted epithelial spheres that in the presence of androgen maintained cell integrity. Coincubation for up to 48 hours of caput epididymal spermatozoa with 3-day-old epithelial cultures from the cauda epididymis was undertaken. MAIN OUTCOME MEASURES: Morphology of epididymal epithelium was assessed by light and electron microscopy. Pulse labeling of tissue in vitro with 35S-methionine was performed with analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis technique and fluorography. Spermatozoa were assessed for progressive motility and their capacity to bind to salt-stored human zona pellucidae. RESULTS: Epididymal fragments formed everted epithelial spheres that maintained cell integrity and functional morphology for 5 to 7 days. Specific proteins were synthesized in culture, in particular, proteins of 20, 22, 40, and 66 kd. Coincubation of caput epididymal spermatozoa with cultures from the cauda epididymis induced a significant increase in progressive sperm motility and sperm binding to salt-stored human zona pellucidae compared with control cultures of epithelium incubated in the absence of androgens or overgrown with fibroblasts. CONCLUSIONS: Aspects of human sperm maturation processes can be mimicked in vitro using coculture techniques with epididymal epithelium. This method may be valuable for improving the fertilizing capacity of human spermatozoa retrieved from the proximal region of the excurrent ducts. PMID- 1426327 TI - Effect of abstinence on sperm acrosin, hypoosmotic swelling, and other semen variables. AB - OBJECTIVE: To compare the variability of sperm acrosin and hypoosmotic swelling to the more standard semen variables in relationship to controlled periods of sexual abstinence using a defined group of men. DESIGN: Ten men abstained sequentially for 1, 2, 3, 4, 5, and 10 days and produced an ejaculate after each time period. The ejaculate variables measured at each time point were sperm acrosin, hypoosmotic swelling, volume, sperm number, sperm concentration, sperm motility, sperm morphology, pH, and white blood cells (WBCs). Comparisons were performed between the values obtained at each abstinence period. RESULTS: The percentage of hypoosmotically reactive spermatozoa did not vary significantly with the abstinence period. Sperm acrosin remained similar up to 5 days of abstinence but decreased almost twofold after 10 days of abstinence. The sperm volume and concentration increased gradually with the length of abstinence, being approximately twofold higher after 10 days of abstinence than after 1 day of abstinence. The total sperm number increased about fourfold from 1 day of abstinence to 10 days of abstinence. The percent normal sperm forms tended to increase until 5 days of abstinence but decreased after 10 days of abstinence. The WBC count showed only a small increase with longer abstinence periods. The pH remained essentially the same. CONCLUSIONS: The length of abstinence affects the various semen variables differently. An abstinence period of up to 10 days does not alter the hypoosmotic swelling test results. However, the sperm acrosin values decrease after prolonged abstinence so that the abstinence period needs to be taken into consideration when performing this assay. PMID- 1426326 TI - Defective function of a nongenomic progesterone receptor as a sole sperm anomaly in infertile patients. AB - OBJECTIVE: To compare the function of a novel nongenomic progesterone (P) receptor on the human sperm surface (mediating the P-induced acrosome reaction) in spermatozoa from fertile donors and from infertile patients. To examine the possible implication of defective P receptor function as an etiologic factor in unexplained male infertility. DESIGN: Progesterone binding and P effects were assessed in sperm from infertile patients and compared with corresponding parameters for sperm from healthy donors. SETTING: Private hospital, medical research center, and a university-based andrological laboratory. PATIENTS, PARTICIPANTS: Sperm samples were from infertile patients (no pathology detected in their wives) attending our infertility clinic and from healthy sperm donors. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Progesterone binding sites were visualized with a fluorescein-labeled protein-P conjugate. Indo 1-AM (a fluorescent indicator of intracellular free Ca2+) was used to measure P-induced Ca2+ influx. Progesterone-induced acrosome reaction was monitored after acrosomal staining with Pisum sativum agglutinin. RESULTS: Among 8 patient sperm samples with normal spermiogram values (of 53 examined), 5 showed a reduced percentage of P-binding spermatozoa and an abnormal response to the hormone in terms of Ca2+ influx and the acrosome reaction. CONCLUSIONS: Defective function of a sperm surface P receptor is described in some cases of male infertility. The observed fluorescence microscopic patterns of hormone binding may be used to further investigate receptor activity in unexplained male infertility. PMID- 1426328 TI - Evaluation of acrosomal status using MH61-beads test and its clinical application. AB - OBJECTIVE: To evaluate the acrosomal status of viable sperm by MH61-beads test and its clinical application. DESIGN: Acrosomal status was evaluated using immunobeads coated with MH61 monoclonal antibody, which is specific for acrosome reacted sperm. When viable sperm was coincubated with MH61-beads for an appropriate length of time, the formation of a sperm-bead complex was observed with a phase-contrast microscope, and the number of sperm binding to MH61-beads increased with the progression of the acrosome reaction. Using this agglutination, we developed the MH61-beads test to assess sperm function. SETTING: Department of Obstetrics and Gynecology, Osaka University Hospital. PARTICIPANTS: Forty-three volunteers and 20 males in our in vitro fertilization (IVF) and embryo transfer program. MAIN OUTCOME MEASUREMENT: The results of MH61 beads test were compared with the percentage of acrosome-reacted sperm detected by Pisium satinum agglutinin staining on 30 volunteers, with the results of sperm penetration assay (SPA) in 43 volunteers, and with the outcome of IVF in 20 patients. RESULTS: The results of MH61-beads test showed good reproducibility and correlated with the results of SPA using zona-free hamster eggs and IVF. CONCLUSIONS: The MH61-beads test, the results of which reflect the acrosomal status of sperm, may provide useful information concerning the fertilizing ability of sperm. PMID- 1426329 TI - Reactive oxygen species generated by human neutrophils inhibit sperm motility: protective effect of seminal plasma and scavengers. AB - OBJECTIVE: To investigate whether activated poly-morphonuclear neutrophils (PMN) can affect sperm motility and to assess the capacity of seminal plasma and of scavengers of reactive oxygen species to prevent any loss of motility. DESIGN: Blood PMN were isolated, and their capacity to generate reactive oxygen species was investigated. The effect of activated PMN was tested on the motility of Percoll-washed spermatozoa in the presence and absence of reactive oxygen species scavengers or seminal plasma (whole or fractionated). PARTICIPANTS: Fertile volunteers and patients attending the Infertility Clinic at the Royal Victoria Hospital. RESULTS: The production of reactive oxygen species by activated PMN occurred in the 1st hour after stimulation and was linearly correlated with the concentration of PMN. Percoll-washed spermatozoa had reduced motility in the presence of PMN, and the drop in motility was more severe as the concentration of PMN was increased. Catalase and dimethylsulfoxide reduced the toxic effect of PMN on sperm motility, whereas superoxide dismutase was without effect. Seminal plasma (50%, vol/vol) allowed a highly variable protective effect against the loss of sperm motility that appeared to originate predominantly from the low molecular weight (< 10 kd) fraction but also from the high molecular weight (> 12 kd) fraction of seminal plasma. CONCLUSION: These data suggest that [1] the presence of PMN, even at 0.6 x 10(6) cells/mL, in semen can be hazardous for spermatozoa, [2] H2O2 and .OH are responsible for the loss of motility, and [3H] seminal plasma confers a variable protection due to high and low molecular weight factors. PMID- 1426330 TI - Evaluation of interceed(TC7) for reduction of postoperative adhesions in rabbits. AB - OBJECTIVE: To evaluate the effectiveness of Interceed(TC7) (Johnson and Johnson, New Brunswick, NJ) in the prevention of postoperative adhesions in a rabbit uterine horn model. Interceed(TC7) was tested in the presence and absence of absorbable suture. DESIGN, SETTING, PARTICIPANTS: Forty-one New Zealand white rabbits had lesions created on bilateral uterine horns at laparotomy. Lesions were randomly allocated to treatment with Interceed(TC7) or control. The effect of Interceed(TC7) was evaluated on sutured lesions (4-0 polyglactin 910; Ethicon, Inc., Somerville, NJ) as well as on open cut lesions (no sutures applied). MAIN OUTCOME MEASURES: Adhesion formation, using a grading system ranging from 0 to 3. RESULTS: Interceed(TC7)-treated animals in the sutured group (average adhesion score +/- SD = 2.15 +/- 1.3) did not differ from controls (average score +/- SD = 2.35 +/- 0.93) in adhesion formation, P = 0.47. Rabbits with open cut lesions treated with Interceed(TC7) (average adhesion score +/- SD = 1.89 +/- 1.1) did not differ from control animals (average score +/- SD = 1.83 +/- 1.2), P = 0.88. CONCLUSIONS: Interceed(TC7) was not an effective adhesioprophylactic agent in the presence or absence of nonreactive absorbable suture. PMID- 1426331 TI - Fertility in a 47,XXY patient: assessment of biological paternity by deoxyribonucleic acid fingerprinting. PMID- 1426332 TI - Hysteroscopic treatment of congenital uterine malformations causing hemihematometra: a report of three cases. AB - To our knowledge, this is the first case report of hysteroscopic treatment of congenital uterine malformations with one-sided occlusion causing hemihematometra. This rare form of uterine anomaly should be considered when symptoms such as increasing pelvic pain start with menarche. A 9-mm resectoscope was used for dissecting the way into the occluded part of the uterine body. There the endometrium was ablated for prevention of recurrence of hemihematometra. By this endoscopic approach the disadvantages of laparotomy could be avoided in three adolescent patients. PMID- 1426333 TI - Canalization failure of the mullerian tract. AB - A patient is described with canalization failure of the mullerian system. This patient presented with primary amenorrhea and absence of the vagina. At the time of laparotomy, a uterus of normal size and shape was found with two small areas of canalization. This syndrome, associated with absence of the vagina, appears to result from a defect occurring later in development than does classical mullerian aplasia. Pathological examination of the patient's uterus supports the tenant that canalization begins after fusion and at various places along the line of fusion. PMID- 1426334 TI - Ovarian cyst aspiration: a therapeutic approach to ovarian hyperstimulation syndrome. AB - Ultrasonographically guided transvaginal aspiration of ovarian cysts in women with severe OHSS after GIFT or IVF was safe and has resulted in immediate relief of symptoms, a shorter disease process, and outpatient treatment. The patients were allowed to go back to normal activity after the procedure. The progression of the disease was interrupted and six of seven patients carried beyond 20 weeks' gestation. PMID- 1426335 TI - The value of repeat hysteroscopic evaluation in patients with failed in vitro fertilization transfer cycles. AB - One hundred ten women with normal initial hysteroscopy who failed to conceive during three or more IVF-ET cycles underwent repeat hysteroscopic evaluation. In 20 patients (18.2%), visualization revealed uterine abnormalities, mainly newly added endometrial lesions, i.e., hyperplasia, polyps, endometritis, and synechiae. Our results indicate that repeat hysteroscopic evaluation, in cases of recurrent IVF-ET failure, is an important adjunctive method for further evaluating and possibly optimizing the IVF-ET procedure. PMID- 1426336 TI - Pregnancy after subzonal insertion of cryopreserved spermatozoa from a patient with testicular seminoma. AB - The first pregnancy established after subzonal insertion of frozen-thawed sperm obtained from a patient with seminoma and severe oligoasthenospermia is reported. A total of 800,000 sperm with a poor progressive motility were recovered after thawing. Three to seven motile spermatozoa were injected into the perivitelline space of each of 10 oocytes, and seven sibling oocytes were coincubated and inseminated with 200,000 motile sperm/mL. Only 1 of the manipulated oocytes fertilized and was transferred to the uterus 65 hours after insemination at the eight-cell stage. A healthy boy weighing 3,600 g was delivered spontaneously at 38 weeks of pregnancy. This report gives hope to patients with testicular malignancy and severely impaired sperm function to maintain their reproductive potential through sperm banking and assisted fertilization techniques. PMID- 1426337 TI - Assessment of sperm for cryopreservation using the hypoosmotic viability test. AB - In summary, the hypoosmotic viability parameter was significantly correlated with the outcome of the thawed sperm motility. The prefreeze supravital staining for sperm viability and the hypoosmotic sperm swelling test were not predictive of the thawed sperm total motility. The hypoosmotic viability parameter was not correlated to the postwarmed sperm motility after refrigeration. The results indicated that the integrity of the sperm membranes at the head were more important than the tail membrane. PMID- 1426338 TI - Very late return of spermatogenesis after chlorambucil therapy: case reports. AB - Two men were treated for a nephrotic syndrome with high-dose chlorambucil therapy; 6.5 and 14 years later, respectively, both were azoospermic with high plasmatic FSH values. Both patients showed active spermatogenesis, 15 and 19 years after the end of the treatment. This suggests that a return of spermatogenesis can occur even after very high cumulative doses of chlorambucil (between 3,000 and 6,500 mg) and after a very long time. PMID- 1426339 TI - Allergic reactions to penicillin during in vitro fertilization and intrauterine insemination. AB - Two cases are reported in which hypersensitivity reactions occurred after intrauterine placement of spermatozoa or embryos. Because the cells were processed and transferred in antibiotic-containing media, these reactions were suspected to be because of penicillin allergy. One patient had no prior penicillin allergy but was found to be penicillin allergic by skin testing. The other had a history of allergy to oral penicillin. In both cases, the allergy symptoms did not occur during subsequent cycles when antibiotics were removed from the transfer media. These reports suggest that in patients known to be penicillin sensitive, penicillin should not be used during transfer of gametes and embryos for assisted reproductive procedures. In addition, the routine use of antibiotics in these procedures should be scientifically evaluated. PMID- 1426340 TI - Digital road mapping image--a novel fluoroscopic real-time guide for selective transcervical catheterization in the treatment of proximal tubal obstruction. AB - Ten infertile women 20 to 40 years of age, with a standard HSG diagnosis of unilateral proximal tubal obstruction, underwent a transvaginal catheterization and recanalization of the fallopian tubes. To set a fluoroscopic real-time guidance technique for improving the results of transvaginal catheterization and recanalization of the fallopian tubes and to increase its marginal safety, catheterization was performed under digital road mapping guidance. Transcervical catheterization resulted in an immediate patency of the obstructed tube in all 10 women. Three women conceived 2 to 3 months after the procedure. The improved catheterization technique enables good results in the diagnosis and treatment of proximal tubal obstructions. PMID- 1426341 TI - The linear everting catheter: a nonhysteroscopic, transvaginal technique for access and microendoscopy of the fallopian tube. AB - The linear everting catheter is a new technology that allows for nonhysteroscopic, transvaginal access, and microendoscopy of the fallopian tube. Initial results indicate that this approach is safe, successful, and offers a number of unique advantages relative to the available alternatives. Studies are in progress to explore several of the many possible applications of this system in the diagnosis and treatment of infertile patients. PMID- 1426342 TI - Intraperitoneal insemination--does it help? PMID- 1426343 TI - Treatment of recurrent ectopic pregnancy. PMID- 1426344 TI - Capacitated or acrosome-reacted sperm? PMID- 1426345 TI - Autoantibodies in in vitro fertilization patients. PMID- 1426346 TI - Protection against antisperm antibodies? PMID- 1426347 TI - Protection against antisperm antibodies? PMID- 1426348 TI - Hysteroscopic resection of uterine septum-instrumentation? PMID- 1426349 TI - Penetration of zona-free hamster oocytes using human sperm aspirated from the epididymis of men with congenital absence of the vas deferens: comparison with human in vitro fertilization. AB - OBJECTIVES: To assess the ability of sperm aspirated from the epididymis of men with congenital absence of the vas deferens to penetrate zona-free hamster oocytes. To directly compare the performance of human epididymal sperm in the zona-free hamster oocyte sperm penetration assay (SPA) with the results of human in vitro fertilization (IVF). DESIGN: Sperm penetration assay was carried out with epididymal sperm retrieved microsurgically, and with ejaculated sperm obtained from fertile donors (internal controls). For direct comparison, SPA was performed with the same epididymal sperm sample used for IVF. PATIENTS, PARTICIPANTS: Men with congenital absence of the vas deferens undergoing sperm aspiration as part of their infertility treatment and control donors who provided ejaculated sperm. RESULTS: Epididymal sperm penetrated SPA with a score of 0% to 30%. The SPA scores for internal controls using ejaculated sperm was 30% to 71%. Linear regression analysis of the association between penetration scores in SPA and fertilization rate in IVF indicated a positive correlation that was highly significative. CONCLUSIONS: These findings using SPA confirm previous reports on the fertilizing potential of human epididymal sperm and its ability to produce normal pregnancies. The good correlation between SPA and human IVF using epididymal sperm suggest that SPA is an excellent bioassay to test laboratory experimental conditions for improving fertilizing capacity of human epididymal sperm. PMID- 1426350 TI - Relationship of epididymal sperm antibodies to their in vitro fertilization capacity in men with congenital absence of the vas deferens. AB - OBJECTIVES: To test, using the immunobead binding technique, for the presence of antisperm antibodies on epididymal sperm, in epididymal fluid, and in serum of men with congenital absence of the vas deferens. To evaluate the in vitro fertilization (IVF) capacity of human epididymal sperm in the presence of antisperm antibodies. DESIGN: Prospective. At the time of oocyte insemination, sperm from the proximal caput epididymis or vasa efferentia were tested by direct immunobinding technique. The epididymal fluid and serum were tested by indirect immunobinding technique. SETTING: Center for Reproductive Health, University of California-Irvine. PATIENTS: Forty-five patients with congenital absence of the vas deferens participating in the microsurgical epididymal sperm aspiration and IVF program. MAIN OUTCOME MEASURE: Incidence of antisperm antibodies to epididymal sperm and their relationship with IVF results. RESULTS: Sixteen men (35%) tested positively to the direct immunobead test on epididymal sperm; 7 (16%) were positive in epididymal fluid and 13 (29%) were positive in serum. Five pregnancies (31%) occurred in the positive group of which two were from patients who had sperm binding of 100% for immunoglobulin (Ig)G (all over sperm surface) and 90% (midpiece, tail) and 50% (tail, tiptail), respectively, for IgA. Five pregnancies (18%) were obtained in the negative group. No statistical difference was observed in the overall fertilization rate between the two groups. CONCLUSION: Human epididymal sperm and epididymal fluid retrieved from men with congenital absence of the vas deferens can react positively to immunobead test. However, the presence of antisperm antibodies do not seem to impair the IVF capacity of epididymal sperm. PMID- 1426351 TI - Characterization of human sperm antigens and antisperm antibodies in infertile patients. AB - OBJECTIVE: To identify which sperm antigens may elicit the production of functionally important antisperm antibodies. DESIGN: Immunoblot analysis was performed on 69 serum and 9 seminal plasma samples from infertile patients, using detergent extracts of pooled donor sperm as the antigen source. Serum and seminal plasma had been previously tested by an indirect immunobead binding test (IBT); 61 IBT-positive and 17 IBT-negative samples were included in the study. Proteins recognized by IBT-positive but not IBT-negative samples were most likely to be cell surface antigens, whereas proteins recognized by both IBT-positive and IBT negative samples were probably intracellular. Antibodies directed toward surface antigens would be most likely to affect fertilization. Characterization of sperm surface proteins on both acrosome-intact and -reacted sperm used labeling of cell surface proteins with an N-hydroxysuccinimide ester of biotin, fractionation of sperm heads and tails, and lectin binding to determine glycosylation. RESULTS: Specific immunoreactivity (with respect to IBT results) was observed to 35K, 40 to 45K, 57K, 66K, and 88 to 90K MW proteins. Characterization studies identified an 88K MW glycosylated plasma membrane protein, a 66K MW inner acrosomal membrane protein, a 34K MW inner acrosomal membrane protein, and a 35K MW prominent tail protein. CONCLUSION: Immunological infertility may involve several antigens characterized in this study. Further studies are necessary to determine if antibodies to these specific proteins interfere with sperm function. PMID- 1426352 TI - Custom cryopreservation of human semen. AB - OBJECTIVE: To design a protocol to evaluate individual variability in human semen cryoprotection by native seminal plasma. DESIGN: Post-thaw motility from the frozen semen of pregnancy-proven donors (n = 10) and patients referred for infertility screening (n = 10) was examined in three equal aliquots (per original ejaculate) that comprised varying ratios of native seminal plasma to TES and Tris (TEST)-yolk buffer (Irvine Scientific, Irvine, CA) in a dose-titration curve format. All aliquots from the same ejaculate contained final vol/vol 6% glycerol, had equal sperm density, and had undergone centrifugation for 5 minutes at 600 x g before buffer:semen ratio adjustment and standard precooling protocol for submersion in liquid nitrogen. Post-thaw measurement of percent original motility preserved (post-thaw percent motility/original percent motility x 100) was used for standardization of results. RESULTS: In 14 of 20 specimens (70%), the maximal yield of original motility was obtained in 50% seminal plasma, with an average post-thaw motile yield of 50%. In 6 of 20 specimens (30%), the best preservation of original motility was noted at 100% seminal plasma, with an average post-thaw motile yield of 58%. No specimen had a greatest percent motility preserved at 0% seminal plasma. Donor specimens have equal preference for either 50% or 100% seminal plasma, whereas patient specimens have a preference for 50% seminal plasma (P < 0.05). CONCLUSIONS: Native seminal plasma has variable cryoprotectant qualities for which custom cryopreservation can compensate. A simple two-point dose-titration test of cryopreservation buffer:seminal plasma ratio (i.e., 50:50 versus 0:100) can determine the optimal mixture for cryopreservation of a given individual's semen. PMID- 1426353 TI - Semen cryobanking for men with cancer--criteria change. AB - OBJECTIVE: To summarize pregnancies and births after the use of pretherapy cryobanked semen from men with cancer and to reassess the clinical role of semen cryobanking for these patients. DESIGN: Survey of pregnancies and births that have occurred after the use of cryobanked semen from pretherapy cancer patients. SETTING: Survey of the literature and of nine semen banks. PATIENTS: Men with testicular cancer, Hodgkin's diseases, non-Hodgkin's lymphoma, and other types of cancer who cryobanked their semen specimens before therapy. OUTCOME MEASURES: Pregnancies and births resulting from the use of cryobanked semen after artificial insemination by husband (AIH) or other assisted reproductive technology (ART) procedures. RESULTS: The use of AIH and other ART procedures have resulted in 117 documented pregnancies and 115 livebirths. CONCLUSIONS: Cryobanking of semen should be offered to all men diagnosed with cancer because such a procedure provides the only reasonable chance of establishing a pregnancy after therapy that is detrimental to fertility potential. Existing criteria for pretherapy semen cryobanking, therefore, should be revised in view of successful pregnancies even with the use of semen with low spermatozoal densities and motilities, as well as other realized clinical efficacies of ART. Conceptions have occurred after in vitro fertilization (IVF) with < 1 x 10(6) motile spermatozoa. Semen cryobanking should be offered by the attending physician as a viable option for any pretherapy male patient who has any motile sperm and considers the future possibility of having children. PMID- 1426354 TI - Assessment of testicular cytology by fine needle aspiration as a diagnostic parameter in the evaluation of the oligospermic subject. AB - OBJECTIVE: To investigate whether testicular cytology by fine needle aspiration may be considered a diagnostic parameter in the evaluation of the oligospermic subject. DESIGN: Cytologic smears were obtained using a 23-gauge needle, stained with May-Grunwald-Giemsa stain and examined under a light Orthoplan microscope (Wild Leitz, Wetzlar, Germany) for qualitative and quantitative analysis. PATIENTS: One hundred sixty-six oligospermic patients were analyzed, and the findings were compared with those obtained from 40 normozoospermic infertile subjects used as controls. MAIN OUTCOME MEASURE(S): At least 200 spermatogenic cells were counted per slide and classified at the various steps of spermatogenesis. Because the number of Sertoli cells may be considered as a constant per unit of tubular length, Sertoli cells:spermatogenic cells ratio (termed Sertoli index) provided further elucidation and more comprehensible results. RESULTS: The procedure provided no sign of traumatization. The cytologic analysis permitted identification of different classes of oligospermic subjects, characterized by the following specific cytologic pictures: [1] bilateral or [2] unilateral germ depopulation (hypospermatogenesis), associated with maturation abnormalities of the first steps of spermatogenesis on both testes; [3] difficult maturation of the immature germ cells (spermatogonial or spermatocytic arrest); [4] ineffective spermiogenesis (spermatidic arrest); [5] normal maturation of the germ line in the presence of oligospermia, resulting from a transient acute damage on the spermatogenic line. Plasma levels of FSH and the testicular volumes agree with the cytologic picture of each group of patients. CONCLUSIONS: The results support use of fine needle aspiration of the testis as a minimally invasive diagnostic parameter for the assessment of oligospermic subjects. PMID- 1426355 TI - Effect of ascorbic acid supplementation on the sperm quality of smokers. AB - OBJECTIVE: To determine the effect of ascorbic acid supplementation on the sperm quality of heavy smokers. DESIGN: Microscopic examination of semen for 1 month during supplementation with placebo or ascorbic acid at dose levels of 200 or 1,000 mg/d. SETTING: Department of Obstetrics and Gynecology, The University of Texas Medical Branch. PARTICIPANTS: Seventy-five men (20 to 35 years old) randomly divided into one of three supplementation groups: placebo, 200 mg and 1,000 mg of ascorbic acid. MAIN OUTCOME: Improvement in sperm quality as compared with presupplementation levels and between the three treatment groups. RESULTS: The placebo group showed no improvement in sperm quality. The groups receiving ascorbic acid showed improvement in sperm quality with most improvement in the 1,000-mg group. Pearson's correlation showed statistically significant relationships between the weekly group means of serum and seminal plasma ascorbic acid levels and sperm qualities. CONCLUSIONS: Ascorbic acid supplementation of heavy smokers in excess of 200 mg/d results in improved sperm quality. PMID- 1426356 TI - Deoxyribonucleic acid flow cytometry and semiquantitative histology of spermatogenesis: a comparative study. AB - OBJECTIVE: To compare deoxyribonucleic acid (DNA) flow cytometry with a semiquantitative histologic method for the assessment of spermatogenesis and to investigate the influence of various preparative techniques on the results of DNA measurements. DESIGN: Testicular tissue from 52 autopsies was examined for spermatogenesis by DNA flow cytometry and by conventional semiquantitative histology. Flow cytometry was performed on single nuclei suspensions from fine needle aspiration biopsies, resuspended imprints, as well as on specimens obtained by mechanical disaggregation of surgical biopsies of the same testis. RESULTS: In all cases, flow cytometry revealed a characteristic distribution pattern of haploid (n), diploid (2n), and tetraploid (4n) cells independent of the preparation technique used. The percentage of haploid cells of the testes showed statistically highly significant correlations (P = 0.0002) with the results of semiquantitative histology. Fine needle aspiration biopsy always contained more haploid cells compared with resuspended imprints and mechanically disaggregated samples. CONCLUSION: Our results confirm the suitability of DNA flow cytometry as a fast and reliable quantitative method for the assessment of spermatogenesis and demonstrate its optimal feasibility in combination with fine needle aspiration biopsy. PMID- 1426357 TI - Differentiation of round cells in semen by means of monoclonal antibodies and relationship with male fertility. AB - OBJECTIVE: To differentiate round cells in semen samples of subfertile men and evaluate the clinical significance during infertility investigation. PATIENTS: One hundred and eight randomly chosen couples with a median duration of infertility of 4 (range, 1 to 20) years presenting at the outpatient infertility clinic of the University of Heidelberg, Germany. MAIN OUTCOME MEASURES: Differentiation of round cells in semen by means of monoclonal antibodies (mABs) and a streptavidin-biotin system for staining. Correlation of results with medical history, outcome of clinical examination, sperm analysis, microbial screening of both partners, evaluation of sperm functional capacity in vivo by means of the postcoital test (PCT) and in vitro with the standardized crossed sperm-cervical mucus penetration test (SCMPT) and the subsequent fertility in a prospective study. RESULTS: The method used for differentiation of round cells proved to be practical and suitable for routine use. The percentage of leukocytes ranged from 0% to 58% with a median of 3%. Number of round cells and percentage of leukocytes did not differ markedly with regard to andrologic history, clinical findings, for example, varicocele, results of standard sperm analysis, and microbial colonization of semen samples. However, high rates of leukocytes of the round cells correlated with reduced sperm count and morphology and results of PCT. Leukocyte-positive (> 15% leukocytes) specimens were also significantly more frequent in case of inadequate SCMPT and reduced sperm penetration ability in vitro. CONCLUSIONS: In asymptomatic patients (in terms of genital tract infection), the majority of round cells consist of immature germ cells and < 5% are white blood cells. The streptavidin-biotin system and the mABs used in this study proved to be useful to identify patients with elevated rates of leukocytes in semen possibly reflecting subclinical genital tract infection with influence on sperm functional capacity and subsequent fertility. Thus the procedure can be recommended to be included in a comprehensive evaluation of male fertility. PMID- 1426358 TI - Autotransfusion of the ascitic fluid in the treatment of severe ovarian hyperstimulation syndrome. AB - Three cases of severe OHSS were treated by transvaginal aspiration of the ascitic fluid and autotransfusion of the aspirated fluid. Marked improvement of the symptoms, general condition, and urine output followed the aspiration shortly. No reactions were noticed during or after the autotransfusion. The blood parameters were corrected, and the general condition and urine output continued to improve. The procedure is simple, safe, and straightforward that showed a striking physiological success in correcting the maldistribution of fluid and proteins without the use of heterogeneous biological material. PMID- 1426359 TI - Isolated prolactin deficiency: a case report. AB - A 36-year-old woman, with lifelong oligomenorrhea and immeasurable serum PRL levels, conceived and had normal deliveries after ovulation induction with CC. Alactogenesis followed both deliveries. Evaluation of other pituitary hormones were within normal limits, and attempted stimulation of PRL levels by TRH was unsuccessful. The clinical significance of isolated hypoprolactinemia is discussed. PMID- 1426360 TI - Magnetic resonance imaging using "fat-saturation" technique is useful for diagnosing small endometrioma: a case report. AB - Preoperative MRI using fat-saturation technique was performed in a patient with endometriosis. Endometrial implants as small as 3 mm were accurately diagnosed by MRI. The fat-saturation technique is useful for diagnosing small endometrioma. PMID- 1426361 TI - Radiologic evaluation of incremental intrauterine instillation of contrast material. AB - In view of the contradictory results of IUI reported in the literature, the present study was undertaken to determine whether the volume of material injected into the uterus can affect the delivery site of the sperm. Ten infertile women scheduled for HSG were submitted to intrauterine injection of different volumes of radiopaque dye (0.2 mL to 1.0 mL) before the procedure to mimic IUI. An x ray taken immediately after injection showed that volumes of > or = 0.4 mL reached the uterus and tubes, whereas the 0.2-mL volume did not reach the tube. These data show that volume injected is an important variable in IUI. PMID- 1426362 TI - Transcervical tubal cannulation: a comparison of two techniques. AB - Transcervical tubal cannulation using tactile guidance has a similar rate of successful cannulation compared with that with US guidance (78% versus 73%) but takes less time to perform (2.3 +/- 1.8 minutes versus 8.7 +/- 6.2 minutes, mean +/- SD) and is associated with less pain and bleeding. This appears to be because of the design of the Labotect tubal cannulation set that uses a special speculum and tenaculum to straighten the uterus before insertion of the guide cannula and a less traumatic ball-tipped guide catheter. PMID- 1426363 TI - Cytogenetics of human spermatozoa: correlations with sperm morphology and age of fertile men. AB - Sperm chromosomes from 15 fertile men were analyzed after fusion of their spermatozoa with zona-free hamster eggs. The total proportion of abnormal metaphases as well as the proportions of aneuploidy and structural aberrations were calculated for every man and examined for linear correlations with [1] sperm morphology and [2] the age of the persons studied. A positive correlation between the cytogenetic parameters and the percentage of abnormal sperm morphology was not evident, suggesting that assessment of sperm morphology cannot be used as an indicator of chromosomal damage in human spermatozoa. In contrast, there was a more distinct positive correlation between the age of donors and the three cytogenetic parameters studied. PMID- 1426364 TI - Hydrogynecography: a new technique enables vaginal sonography to visualize pelvic adhesions and other pelvic structures. AB - Vaginal ultrasonography, done after the transcervical injection of isotonic saline into the cul-de-sac, is a new technique we named hydrogynecography. This was prospectively used in patients suffering from infertility and pelvic pain. In 84% of patients we were able to identify pelvic adhesions confirmed by laparoscopy. In 16% the procedure provided false-negative results. PMID- 1426365 TI - Laparoscopic removal of 46XY gonads located within the inguinal canals. AB - Male pseudohermaphrodites require gonadectomy for the prevention of gonadal malignancy. Laparoscopic gonadectomy has been performed in patients with intra abdominal gonads and can also be performed in patients whose gonads are located within the inguinal canals. PMID- 1426366 TI - A microwell sperm penetration assay. AB - Egg penetration rates in a modified SPA using microwells in tissue typing plates were comparable with those in a standard assay. This technique allows sperm penetrating ability to be determined using single zona-free hamster eggs and as few as 10,000 spermatozoa. PMID- 1426367 TI - Selecting against "unfit sperm". PMID- 1426368 TI - Mutations in the aromatase gene and their effect. PMID- 1426369 TI - Graft versus host or host versus graft reaction after paternal immunization. PMID- 1426370 TI - Neural tube defects after infertility treatment: a review. AB - OBJECTIVE: To investigate whether an association exists between ovulation induction and neural tube defects (NTDs). MATERIALS AND METHODS: Risk estimations in the medical literature were identified through Medline, and validity and power were assessed. Large in vitro fertilization-embryo transfer (IVF-ET) registries represent another source of information. The total number of NTDs and the total number of fetuses were computed from five registries. These data were expressed as proportions and compared with data from the general population. RESULTS: Only one study could be identified as both valid and powerful, through literature review. This case-control study concluded there was no association between ovulation induction and NTDs. The pool of IVF-ET registry data represents another powerful epidemiologic tool. Analysis of the registry data confirms the findings of the case-control study. CONCLUSIONS: Ovulation induction does not seem to represent a risk factor for NTDs in the offspring. PMID- 1426371 TI - Gynecoradiology: a new approach to diagnosis and treatment of tubal disease. PMID- 1426372 TI - The routine use of gonadotropin-releasing hormone agonists prior to in vitro fertilization and gamete intrafallopian transfer: a meta-analysis of randomized controlled trials. AB - OBJECTIVE: To assess the efficacy of gonadotropin-releasing hormone agonists (GnRH-a) used in ovulation induction for in vitro fertilization and embryo transfer (IVF-ET) and gamete intrafallopian transfer (GIFT). DESIGN: Meta analysis of 10 trials comparing treatment cycle outcomes after GnRH-a (n = 914) with other ovulation induction protocols (n = 722) and 7 trials comparing outcomes after short flare-up (n = 368) with longer suppression (n = 476) GnRH-a protocols. MAIN OUTCOME MEASURES: The outcome of primary interest was clinical pregnancy rate (PR) per treatment cycle commenced. Data describing the amount of gonadotropin used, cycle cancellation rate, clinical pregnancy per ET, and multiple pregnancy and abortion rates were also analyzed. RESULTS: Clinical PR per cycle commenced was significantly improved after GnRH-a use for IVF (common odds ratio [OR] 1.80, 95% confidence interval [CI] 1.33 to 2.44) and GIFT (common OR 2.37, 95% CI 1.24 to 4.51). Clinical PR per embryo transfer was also significantly improved with GnRH-a use (common OR 1.40, 95% CI 1.01 to 1.95). Cycle cancellation was decreased (common OR 0.33, 95% CI 0.25 to 0.44), whereas spontaneous abortion rate was similar with and without GnRH-a use. Cycle cancellation and PRs after short flare-up and longer suppression protocols were similar between groups. CONCLUSIONS: This meta-analysis supports the routine use of GnRH-a for IVF and GIFT. Further research is needed, however, to assess the potential for increased rates of multiple pregnancy and ovarian hyperstimulation syndrome, which may be associated with this treatment. PMID- 1426373 TI - Color Doppler ultrasonography assessment of tubal patency: a comparison study with traditional techniques. AB - OBJECTIVE: To compare the results of color Doppler ultrasonic hysterosalpingography (color US-HSG) and x-ray-HSG with chromoperturbation at the time of laparoscopy. DESIGN: Open, uncontrolled study of women seeking evaluation for infertility from August 1989 to July 1991. SETTING: Clinical environment. PATIENTS: Two hundred thirty-eight infertile women. INTERVENTION: Saline was administered transcervically during transvaginal color Doppler sonography in 238 women. Traditional x-ray-HSG was performed in 89 women. Laparoscopy with chromoperturbation was done in 121 women. Forty-nine women had all three procedures performed. MAIN OUTCOME MEASURES: The frequency of diagnosis of bilateral tubal patency, bilateral tubal occlusion, and unilateral tubal patency after color US-HSG and x-ray-HSG was compared with chromoperturbation. The diagnostic efficacy of color US-HSG and x-ray-HSG was compared with chromoperturbation. RESULTS: Correlation between color US-HSG and x-ray findings with chromoperturbation occurred in 81% versus 60% (P = 0.0008) of all women studied. In 49 women who had all three procedures performed, color US-HSG results correlated with chromoperturbation more often than x-ray-HSG (82% versus 57%, P = 0.0152). CONCLUSION: Color US-HSG is an alternative technique to x-ray-HSG in diagnosing tubal occlusion as a cause of infertility. PMID- 1426374 TI - Fallopian tubes and ultrasonography: the Sion experience. AB - OBJECTIVE: To compare the accuracy of three new ultrasonographic methods of detecting tubal patency and pathology with established methods like hysterosalpingography (HSG) and laparoscopy. DESIGN: Sixty-seven cases were evaluated by performing the Sion test using endosonography to check for tubal patency. The Sion procedure includes filling up the pouch of Douglas with approximately 300 mL of sterile normal saline to elucidate not only the patency but visualize the motility, the fimbriae, and peritubal adhesions, if present. We have compared the accuracy of this procedure with HSG and laparoscopy in 24 infertile women. Color-coded duplex Doppler sonography was used in 38 patients to check for tubal patency. RESULTS: Our experience at the Sion Hospital using the three new ultrasonographic techniques for evaluating the status of the fallopian tubes is very encouraging. The accuracy with the three modes shows agreement in > 90% of cases with established investigative modalities such as HSG and laparoscopy. CONCLUSION: These three new investigative modalities are offered not as substitutes for HSG, laparoscopy, hysteroscopy, or salpingoscopy but as office screening procedures that would be complementary to the armamentarium of infertility investigations already available. PMID- 1426375 TI - Gonadotropin-releasing hormone-associated peptide gene sequences in women with hyperprolactinemia. AB - OBJECTIVE: To determine if mutations in the structural gene for gonadotropin releasing hormone (GnRH)-associated peptide are present in women with hyperprolactinemia. DESIGN: Patients with hyperprolactinemia and controls were studied retrospectively for GnRH-associated peptide gene mutations. SETTINGS: Patients seen in a clinical setting were studied at a medical school laboratory setting. PATIENTS: Fifteen women with hyperprolactinemia and two fertile controls with normal prolactin levels were studied. INTERVENTIONS: Genomic deoxyribonucleic acid (DNA) was extracted from each patient and subjected to Southern blot analysis and polymerase chain reaction (PCR). For Southern blot analysis, DNA was digested with EcoRI, XbaI, BglII, PstI, and BamHI and hybridized to two DNA probes for GnRH-associated peptide. Exons II to IV, which encode for the structural gene, were amplified by PCR. MAIN OUTCOME MEASURES: Fragment sizes from autoradiographs were compared among patients and controls. Amplified PCR products of exons II to IV of the GnRH-associated peptide were also compared. RESULTS: No large deletions, insertions, or polymorphisms were identified in women with hyperprolactinemia or controls by Southern blotting. Each of the exons was present and of normal size by PCR in the study patients and controls. CONCLUSIONS: No large deletions of the GnRH-associated peptide gene appear to be present in our patients with hyperprolactinemia. Small deletions, insertions, or point mutations are not excluded by this analysis. PMID- 1426376 TI - Absence of effect of adjuvant growth hormone therapy on follicular responses to exogenous gonadotropins in women: normal and poor responders. AB - OBJECTIVE: To examine the effects of growth hormone (GH) on ovarian responses to exogenous gonadotropins after pituitary desensitization in normal and poor responder patients undergoing in vitro fertilization. DESIGN: A prospective study with comparison of control and GH-treated cycles. PATIENTS: Poor responder patients (n = 10) required > 44 ampules of human menopausal gonadotropin (hMG) to achieve criteria for administration of human chorionic gonadotropin (hCG) on day 0 or cancellation in control cycles, and normal responder patients (n = 10) required < 45 ampules. MAIN OUTCOME MEASURES: Ovarian responses to hMG assessed by duration of stimulation required to achieve first significant estradiol (E2) response and hCG criteria. Total doses and duration of hMG, follicular development and E2 concentrations on day 0, and embryology were also assessed. RESULTS: Growth hormone showed no effect on any of the parameters studied in either patient group. CONCLUSION: Follicular recruitment, E2 secretion by mature follicles, and oocyte yield and quality were uninfluenced by GH treatment. PMID- 1426377 TI - Deep endometriosis: a consequence of infiltration or retraction or possibly adenomyosis externa? AB - OBJECTIVE: To analyze the incidence and occurrence of subtypes of deep endometriosis. DESIGN: Deep endometriotic lesions (> 5 mm) were retrospectively analyzed, using our data base and slides taken systematically during surgery. SETTING: University Hospital Gasthuisberg (University of Leuven) which is a referral center for infertility and endoscopic surgery. PATIENTS: All women with deep endometriosis (n = 136) were selected from a consecutive series of 1,252 laparoscopies for infertility, pain, or both. INTERVENTIONS AND MAIN OUTCOME MEASUREMENTS: Deep endometriosis was excised by CO2 laser and the depth of infiltration and the pelvic area measured. As part of an ongoing study, most lesions were photographed. RESULTS: Deep endometriosis is suggested to contain three subgroups. Type I is conical shaped and suggested to be formed by infiltration. Type II is deeply located and covered by extensive adhesions and probably formed by retraction. Type III is a spherical nodule with its largest dimension under the peritoneum. Types I, II, and III are found in 4.1%, 0.8%, and 0.9% of women with infertility (n = 759) and in 10.4%, 3.2%, and 3.2% of women with pelvic pain (n = 374). Types I, II, and III are most frequently found in the revised American Fertility Society classes II, III to IV, and I, respectively. CONCLUSIONS: Three subtypes of deep endometriosis can be distinguished. Type III, which is a spherical nodule located in the recto vaginal septum is the most severe and largest lesion. This is, however, easily missed clinically because these lesions are generally scored as revised American Fertility Society class I. PMID- 1426378 TI - Early endometriosis invades the extracellular matrix. AB - OBJECTIVES: To investigate whether the aminoterminal propeptides of type III procollagen are increased in patients with early endometriosis and to demonstrate that the subtle lesion of endometriosis is an active stage of the disease. DESIGN: Aminoterminal propeptide of type III procollagen was determined in serum and peritoneal fluid (PF) of 100 consecutive patients undergoing laparoscopy. SETTING: Academisch Ziekenhuis Maastricht, The Netherlands, a tertiary care center. RESULTS: Aminoterminal propeptide PF levels were significantly higher in women with early lesions of endometriosis compared with levels in two groups of controls, i.e., fertile, cycling, women without the disease (P = 0.019) and women on oral contraceptives without the disease (P = 0.036). No difference was found in aminoterminal propeptide PF levels when comparing patients with early lesions of endometriosis and patients with unexplained infertility, the third control group. Aminoterminal propeptide PF levels of patients with endometriosis without early lesions were not different from PF levels in controls. CONCLUSION: The early lesion is an active stage of endometriosis, invading the extracellular matrix. In women with unexplained infertility active, microscopic endometriosis may be present. PMID- 1426379 TI - Tumor necrosis factor alpha in the human ovary: presence in follicular fluid and effects on cell proliferation and prostaglandin production. AB - OBJECTIVE: To examine the concentration of tumor necrosis factor alpha (TNF alpha) in human follicular fluid (FF) and its effects on cultured human granulosa lutein cells. DESIGN: The concentration of TNF alpha in FF from hyperstimulated cycles and in conditioned media from cultured granulosa-lutein cells was measured by radioimmunoassay (RIA) and bioassay using L929 cells. The effects of recombinant human TNF alpha (rTNF alpha) on proliferation and production of progesterone (P) and prostaglandin (PG, PGE2, and PGF2 alpha) by cultured human granulosa-lutein cells were assessed. SETTING: In vitro fertilization and embryo transfer (IVF-ET) program at Reproductive Medicine Unit, The Queen Elizabeth Hospital, Woodville, South Australia, Australia. PATIENTS: Twenty-five women undergoing IVF-ET for tubal factor infertility. RESULTS: The concentration of immunoreactive TNF alpha in FF was 0.36 +/- 0.02 microgram/L, and there were no significant correlations between levels of TNF alpha and steroids or FF volume. Bioactivity for TNF alpha was considerably less. Immunoreactive or bioactive TNF alpha was not detected in conditioned media from granulosa-lutein cell culture. Recombinant human TNF alpha dose-dependently stimulated proliferation of cultured granulosa-lutein cells as measured by incorporation of 3H-thymidine, but in contrast to earlier reports, we were not able to demonstrate any effect of rTNF alpha on basal or human chorionic gonadotropin-stimulated P accumulation during culture periods of up to 72 hours. The accumulation of both PGE2 and PGF2 alpha was dose-dependently increased by rTNF alpha during a 48-hour incubation period. Time course studies revealed that maximal levels of both PGE2 and PGF2 alpha were reached within 12 hours of culture. CONCLUSION: Immunoreactive and bioactive TNF alpha is present in FF. Tumor necrosis factor alpha may have a physiological role in stimulating proliferation of follicular cells and PG production at the time of ovulation and formation of the corpus luteum. PMID- 1426380 TI - Inhibitory effect of interferon and tumor necrosis factor on human luteal function in vitro. AB - OBJECTIVE: To investigate whether immunological mechanisms may be involved in human luteal function. DESIGN: The effects of the cytokines, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF alpha) on steroidogenesis by human luteal cells were examined in vitro. The dispersed human luteal cells, obtained from a total of 17 women at laparotomy, were cultured separately in the presence or absence of human chorionic gonadotropin (hCG) and IFNs/TNF-alpha with the medium being replaced at 48 hours. The medium was collected at 48 and 96 hours for steroid assays. RESULTS: The IFN alpha had no significant effect on the production of estradiol or progesterone (P), whereas a dose-related inhibition of basal, as well as hCG-stimulated P formation, was observed after the addition of IFN-gamma (10 to 1,000 U/mL). Progesterone production was inhibited to about 45% of the control at 48 hours and even lower at 96 hours (n = 6, P < 0.001). The combination of IFN-gamma and low doses of TNF-alpha induced a further significant inhibition, whereas there was no effect of TNF-alpha alone. This inhibitory effect of IFN-gamma could be completely neutralized with a monoclonal antibody to IFN-gamma. Incubation with the antibody alone increased the production of P from luteal cells in culture, suggesting a local tonic inhibitory action of endogenous IFN-gamma. CONCLUSION: Interferon-gamma and TNF-alpha, whose function classically is known as antiviral, also may play a role in human luteal regression by inhibiting luteal P production. PMID- 1426381 TI - Antisperm antibodies in women: variability in antibody levels in serum, mucus, and peritoneal fluid. AB - OBJECTIVE: To look for patterns of antisperm antibody expression in women by exploring the levels of antisperm antibodies in different body fluids. This was achieved by studying sequential serum samples from individual patients and by comparing the levels of antisperm antibodies in serum from a number of patients with the levels of antisperm antibodies in cervical mucus or peritoneal fluid (PF). DESIGN: Prospective studies were performed on sequential serum samples within a menstrual cycle. Retrospective studies were done to compare antisperm antibodies in serum and mucus or PF. The immunobead assay was used to measure antisperm antibodies in these fluids. SETTING: Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. PATIENTS: A random sample of patients undergoing evaluation for infertility. RESULTS: The levels of antisperm antibodies in sera drawn from patients at different points in a menstrual cycle stimulated by the presence of exogenous hormones did not change during the follicular phase of the menstrual cycle. Also, in many samples, the antisperm antibody level in serum did not correlate with the antisperm antibody levels in mucus or PF. CONCLUSIONS: The data suggest that measurement of antisperm antibodies at a single point in time or from a single fluid is not sufficient when evaluating a woman for immunological infertility. The data also suggest that numerous and complex factors contribute to the expression of antisperm antibodies in women. PMID- 1426382 TI - Differential effects of transdermal estradiol and sequential progestogens on impedance to flow within the uterine arteries of postmenopausal women. AB - OBJECTIVE: To investigate the relationship between estradiol (E2), progestogen, and impedance to blood flow in the uterine artery. SUBJECTS: Twelve postmenopausal women treated for two cycles with transdermal E2, 0.05 mg/d, with either norethindrone acetate, 0.7 mg, or medroxyprogesterone acetate, 10 mg added sequentially. MEASUREMENTS: Transvaginal ultrasonography and color flow imaging were used to measure the pulsatility index in the uterine arteries before and during the E2-only and combined E2/progestogen phases. RESULTS: The mean pulsatility index fell to 53% of its pretreatment value within 12 days E2 administration (P < or = 0.0001) and was 66% of its pretreatment value in the combined phase (P < 0.005). Similar changes were seen in cycle 2. Time since menopause was correlated with the pretreatment pulsatility index (r = 0.674, P < 0.05) and change in pulsatility index on treatment (r = 0.856, P < 0.001). CONCLUSION: Gonadal hormones have a profound effect on arterial tone in postmenopausal women; this action may help explain some of the beneficial effects of estrogen on arterial disease risk. PMID- 1426383 TI - Further study and characterization of the yellow pigments in follicular fluid that are related to oocyte quality. AB - OBJECTIVE: To characterize the 455-nm (yellow) absorbing pigments in human follicular fluid (FF). DESIGN: Serum and FF samples obtained from patients undergoing in vitro fertilization were analyzed for carotenoids, bilirubin, and beta-glucuronidase concentrations. Spectrophotometric analysis in the visible spectrum was performed on FF samples, and the delta OD455 absorbance was calculated. RESULTS: Thin-layer chromatography confirmed the presence of beta carotene and bilirubin in FF. The mean (+/- SD) contribution of bilirubin and carotenoids to the FF delta OD455 absorbance was 64% +/- 9.6% and 22.7% +/- 12.1%, respectively. Bilirubin fractions in serum and FF samples were then compared. The median unconjugated bilirubin concentration in FF was lower than that in the serum (0.130 versus 0.288 mg/dL; P < 0.0001). The median conjugated bilirubin concentration was higher in the FF when compared with the serum (0.129 versus 0.101 mg/dL; P = 0.0018). beta-Glucuronidase levels in the FF were significantly lower when compared with serum concentrations. CONCLUSIONS: Bilirubin is the major contributor to the FF 455-nm spectrophotometric peak. The higher levels of conjugated bilirubin noted in the FF could in part be explained by the lower levels of beta-glucuronidase. PMID- 1426385 TI - Freezing cocultured human blastocysts. AB - OBJECTIVE: To determine the possibility of obtaining good pregnancy rates (PRs) after freezing and thawing cocultured blastocysts. DESIGN: Human blastocysts were frozen first according to a protocol available from literature. Two other protocols including the addition of glycerol were designed to improve the results. SETTING: All the patients were under clinical management at the Institut Rhonalpin pour l'Etude de la Reproduction Humaine in Lyons, France. PATIENTS: Patients involved in the in vitro fertilization program have had their supernumerary embryos frozen according to the three protocols presented here. MAIN OUTCOME MEASURES: Embryo recovery after freezing and thawing. Clinical and ongoing pregnancies after embryo transfer (ET). RESULTS: A protocol including sucrose addition and reduction of steps in the preparation of the blastocysts for freezing gave us a 21% PR per transfer (15 ongoing) of 101 transfers (106 thawings). CONCLUSIONS: Freezing of cocultured human blastocysts allow good PRs. This can represent an alternative for repeated failures of ETs at early stages. PMID- 1426384 TI - Human embryo biopsy on the 2nd day after insemination for preimplantation diagnosis: removal of a quarter of embryo retards cleavage. AB - OBJECTIVE: To assess any reduction in viability and development in vitro after biopsy of a quarter of the cells of human embryos on day 2 after insemination. DESIGN: A prospective study in which normally fertilized surplus embryos of good morphology with two to eight cells approximately 48 hours after insemination were randomly allocated to a control or biopsied group, respectively. SETTING: In vitro fertilization (IVF) unit and laboratories of the Hammersmith Hospital, Institute of Obstetrics and Gynaecology, London University. PATIENTS, PARTICIPANTS: One hundred twenty-nine embryos from 28 infertile IVF patients. INTERVENTIONS: Follicular aspiration by ultrasound-guided transvaginal puncture and embryo biopsy by micromanipulative procedures. MAIN OUTCOME MEASURE(S): Pyruvate uptake and cell number at the blastocyst stage. RESULTS: Embryo biopsy did not have an adverse effect on either the proportion developing to the blastocyst stage (50% [32 of 64] and 47.7% [31 of 65] for the control and biopsied groups, respectively) or embryo viability, measured indirectly through pyruvate uptake. However, the proportion of embryos that reached the morula stage after day 4 (retarded embryos) was significantly higher (44%, 11 of 25 versus 8.7%, 2 of 23) in the biopsied group. The total number of cells (29.6 +/- 3.1 versus 62.4 +/- 4.7), numbers of inner cell mass (7.7 +/- 2.2 versus 24.5 +/- 1.4) and trophectoderm (24.0 +/- 5.2 versus 45.0 +/- 6.4) cells, and the inner cell mass:trophectoderm ratio (34.7 +/- 7.9 versus 59.5 +/- 11.7) were strikingly reduced at the blastocyst stage in the biopsied group. This reduction was greater in embryos that reached the morula stage after day 4. CONCLUSIONS: More investigation is needed to assess whether the detrimental effects observed were because of the biopsy method used in this study or to a high sensitivity of human embryos at early stages to manipulation in vitro. PMID- 1426386 TI - Effects of smoking on ovulation induction for assisted reproductive techniques. AB - OBJECTIVE: To determine the effects of smoking on ovulation induction for assisted reproductive techniques. DESIGN: Matched, retrospective, cohort study. SETTING: Outpatient University endocrine/infertility program. PATIENTS: Eighteen smokers and 36 nonsmokers: 2 nonsmokers matched to each smoker for age, weight, and history of ovarian surgery. MAIN OUTCOME MEASURES: During a stimulation cycle, the serum estradiol (E2) level, number of follicles, number of oocytes, number of embryos, and ampules of gonadotropins used were compared in the smoking versus the nonsmoking groups by Wilcoxon's signed rank test for paired data. Follicular fluid (FF), testosterone (T), androstenedione (A), E2, A:E2 ratios, and T:E2 ratios were measured and compared between groups by Mann-Whitney U tests. RESULTS: Smokers had significantly lower serum E2 levels, fewer follicles, fewer oocytes retrieved, and fewer embryos per cycle than nonsmokers, despite equal amounts of gonadotropin administration. Follicular fluid obtained from mature follicles had a higher A:E2 ratio and a higher T:E2 ratio in smokers compared with nonsmokers. CONCLUSIONS: Smoking adversely affects ovulation induction parameters and alters the FF hormonal milieu. PMID- 1426387 TI - The relative success of gonadotropin-releasing hormone analogue, clomiphene citrate, and gonadotropin in 1,099 cycles of in vitro fertilization. AB - OBJECTIVES: To evaluate the effectiveness of and analyze the factors influencing the outcome of three ovarian stimulation protocols used during in vitro fertilization (IVF) in a large population. DESIGN: Retrospective file review. SETTING: In vitro fertilization program in one center during the years 1985 to 1990. PATIENTS AND PROTOCOLS: Three hundred forty-one patients received clomiphene citrate (CC) and human menopausal gonadotropin (hMG), 365 received hMG alone, and 393 received gonadotropin-releasing hormone analogue (GnRH-a) for pituitary suppression followed by hMG stimulation. MAIN OUTCOME MEASURE: Rates of cancellation, total pregnancies, and ongoing pregnancies, with breakdown by age of patients. RESULTS: The cancellation rate because of early luteinization following GnRH-a/hMG was significantly reduced compared with the other two protocols: 3.6% versus 9.4% and 13.7% for CC/hMG and hMG, respectively. However, in women over 40 years of age, GnRH-a/hMG resulted in the highest rate of poor ovarian response. Significantly more oocytes were retrieved, fertilized, and cleaved after the use of GnRH-a/hMG compared with the other two protocols. Despite this, clinical pregnancy rate (PR) was the highest with CC/hMG compared with GnRH-a/hMG and hMG:31.4% versus 16.9% and 15.7%, respectively. Ongoing PRs were 20.5%, 9.7%, and 11.6%, respectively. CONCLUSIONS: Although the use of GnRH a for pituitary suppression before ovarian stimulation for IVF reduced the cancellation rate and increased the number of retrieved oocytes, it was not found to result in higher PRs than those achieved by stimulation with CC/hMG. This suggests that treatment by GnRH-a/hMG should be reserved mainly for the prevention of early luteinization. PMID- 1426388 TI - The comparison of two gonadotropin-releasing hormone agonists in an in vitro fertilization program. AB - OBJECTIVE: To compare two gonadotropin-releasing hormone agonists (GnRH-a), buserelin acetate and leuprolide acetate [LA], used in combination with gonadotropins in ovarian stimulation for in vitro fertilization (IVF). DESIGN: Randomized prospective study. SETTING: Assisted Reproduction Unit of the Hospital Clinic i Provincial in Barcelona. PATIENTS: Thirty-five pairs of IVF patients who were matched on age, indication, and number of attempts. These women were randomized to receive either buserelin acetate plus gonadotropins (group B) or LA plus gonadotropins (group L). MAIN OUTCOME MEASURES: Luteolysis, ovarian response, and IVF outcome. RESULTS: The mean time for total ovarian arrest and the total dose of gonadotropins and estradiol levels on the day of human chorionic gonadotropin administration were similar in the two groups of patients. The number of follicles punctured, the number of oocytes retrieved, and the percentage of mature oocytes in group L were significantly higher. The number of embryos suitable for replacement and cryopreservation was higher in group L compared with group B approaching statistical significance. CONCLUSION: Our results warrant further studies to compare different GnRH-a as therapeutic tools in IVF. PMID- 1426389 TI - Intrauterine insemination after ovarian stimulation as a treatment for subfertility because of subnormal semen: a prospective randomized controlled trial. AB - OBJECTIVE: To determine whether intrauterine insemination (IUI) after ovarian stimulation with human menopausal gonadotropin (hMG) gives a better pregnancy rate (PR) than natural intercourse in couples with subfertility because of subnormal semen. DESIGN: Prospective randomized controlled trial. SETTING: University based subfertility clinic. PATIENTS: Couples with subnormal semen as the only identifiable cause of subfertility. INTERVENTIONS: In control cycles, the couples had natural intercourse. In IUI cycles, IUI was performed after ovarian stimulation with hMG and human chorionic gonadotropin. MAIN OUTCOME MEASURE: The clinical PRs and complications of IUI cycles and control cycles were compared. RESULTS: There were six clinical pregnancies in the 42 IUI cycles, whereas there was no clinical pregnancy in the 42 control cycles. The clinical PR in IUI cycles (14.3% per cycle) was significantly higher than that in control cycles (0%). Six patients (14.3%) developed moderate degree of ovarian hyperstimulation syndrome in IUI cycles. CONCLUSION: Intrauterine insemination after ovarian stimulation with hMG is useful in treatment of subfertile couples with subnormal semen. PMID- 1426390 TI - Advances in the understanding of retinitis pigmentosa. PMID- 1426391 TI - When are simple flashes and floaters ocular emergencies? AB - One hundred and seventy patients presented to the Bristol Eye Hospital casualty department with flashes and/or floaters during a six month prospective study. A sight-threatening condition was found in 41 patients (24.1%), the most important of which was a retinal break (16.5%). Although there were no specific symptoms which could be correlated to an increased incidence of retinal breaks, those patients who complained of isolated uniocular floaters had an insignificant incidence of breakage, when compared to asymptomatic fellow eyes. Thus while the majority of patients with flashes and floaters do merit an urgent ophthalmological opinion, those who complain of a single, isolated floater can safely be reviewed as routine outpatients. PMID- 1426392 TI - A comparison of prophylactic, topical and subconjunctival treatment in cataract surgery. AB - Prophylactic subconjunctival antibiotics and steroids have been used in cataract surgery since the early 1950s. However despite their widespread acceptance, there has, to date, been no direct comparison of subconjunctival and topical routes of administration. We therefore carried out a prospective comparison of the effects of subconjunctival and topical administration of antibiotics and steroids in sixty patients undergoing elective, uncomplicated, extracapsular cataract extraction and posterior chamber lens implantation. The patients were examined by a single observer on the first and third post-operative days and two and six weeks following surgery. The observer was blinded to the patient treatment group. Significantly higher degrees of conjunctival injection and anterior chamber activity were noted in those who received subconjunctival injections compared with those who received topical treatment. There were no significant differences between the two groups in best corrected visual acuity, central corneal oedema, cystoid macular oedema, intraocular pressure and infection. We conclude that prophylactic subconjunctival therapy in uncomplicated cataract surgery is not necessary. PMID- 1426393 TI - The uses and limitations of intraocular biopsy. AB - Based upon the author's considerable experience of trans-scleral resection of malignant melanoma of the choroid, a technique has been developed for the biopsy of tissues of the posterior segment of the eye. Its use in the management of atypical malignancy posing diagnostic difficulty and in the investigation of selected case of acute retinal necrosis, uveitis and retinal pigment epitheliopathy is described. In 34 trans-scleral biopsies of choroid, RPE and in some cases, retina, an adverse result occurred in only one case, this it was thought being due to not including pars plana vitrectomy as part of the biopsy technique. Pars plana vitrectomy is now regarded as an integral part of this form of biopsy. PMID- 1426394 TI - The safety and efficacy of topical norfloxacin compared with chloramphenicol for the treatment of external ocular bacterial infections. The Norfloxacin Chloramphenicol Ophthalmic Study Group. AB - Two hundred and forty-six patients with signs of acute bacterial conjunctivitis and/or blepharitis were randomised to receive either norfloxacin or chloramphenicol for one week in this double-masked parallel group study. Ninety two per cent of the norfloxacin-treated patients and 93% of the chloramphenicol treated patients were rated as either clinically improved or cured at the end of the treatment period. Based upon pre-treatment bacteriological cultures, 31.3% of the patients had significant bacterial infection of the lids and/or conjunctiva. All of these culture-positive patients were rated as either clinically improved or cured. Based upon post-treatment cultures, 72 of 82 strains of Gram-positive and Gram-negative bacteria were eradicated or suppressed following treatment with either norfloxacin or chloramphenicol. However six of 41 strains persisted for norfloxacin and four of 41 for chloramphenicol. Two norfloxacin-treated patients and three chloramphenicol-treated patients had adverse experiences, predominantly ocular discomfort, which required cessation of drug therapy. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the lids and/or conjunctiva. In this study, norfloxacin was clinically and microbiologically similar in activity to chloramphenicol. PMID- 1426395 TI - Disinfection of tonometer prisms and examination contact lenses in ophthalmic departments. PMID- 1426396 TI - Cystoid macular oedema following neodymium:YAG laser capsulotomy a prospective study. AB - Neodymium:YAG laser capsulotomy was performed in 65 eyes of 65 patients because of vision loss due to posterior capsular opacification or wrinkling following uneventful extracapsular cataract extraction with intraocular lens implantation. Eyes with pre-existing macular pathology were excluded from this study. In all of the eyes the posterior capsule was successfully opened. None developed clinical or angiographic cystoid macular oedema. One eye developed retinal detachment nine months after capsulotomy. PMID- 1426397 TI - Low contrast visual acuity changes in human immuno-deficiency virus (HIV) infection. AB - A pilot study of low contrast visual acuity testing using Regan Charts has been undertaken in 34 patients seropositive for Human Immuno-Deficiency Virus and 20 normal control subjects. Low contrast visual acuities of the HIV (+) patients both with and without HIV retinopathy were found to be significantly lower than the age-matched controls (p < 0.01). This finding is probably attributable to pathology related to HIV in the visual pathways/Central Nervous System. Lowest contrast Chart (Chart C) was found to be a useful diagnostic tool for HIV retinopathy and presumed neuropathy. PMID- 1426398 TI - Does computerised perimetry offer practical advances in choice of therapy in the glaucoma patient? PMID- 1426399 TI - Do computerised visual fields and automated optic disc analysis assist in the choice of therapy in glaucoma? AB - The choice of therapy in patients with glaucoma is determined by the presence of damage in the visual field or optic disc or by change in the appearance of the optic disc or visual field over time. Computerised visual fields and automated optic disc analysis can assist in this determination. Automated optic disc analysis permits the measurement of neuroretinal rim area which is more closely related to the presence of pathology than cup/disc ratio. Simple ophthalmoscopic techniques may also be used to estimate the size of the neuroretinal rim area. Automated perimetry allows accurate diagnostic information to be obtained in a reliable manner. This permits easier diagnosis of glaucoma as well as easier long term follow up for change. The availability of automated techniques in ophthalmology has helped the clinician in the choice of therapy. The use of astute clinical judgement remains however of the utmost importance. PMID- 1426400 TI - Biometry and auto-fluorescence of the anterior ocular segment in diabetics with and without autonomic neuropathy: a case control study. AB - The biometry and auto-fluorescence of the anterior ocular segment were examined in a case control study of two populations of diabetics. Cases, with diabetic autonomic neuropathy, and controls without neuropathy (forty in each group) were selected from a community based diabetic population and matched individually for age, sex, and type of diabetes. Scheimpflug and auto-fluorescence anterior segment photography were performed and analysed by digital image analysis in a masked fashion. There were differences between the groups in axial lens thickness, front radius of curvature of the lens, anterior chamber depth and lenticular auto-fluorescence. These findings are discussed in the context of the known association between autonomic neuropathy and narrow angle glaucoma, and possible common mechanisms of tissue damage in diabetes. PMID- 1426401 TI - Changes in light scatter and width measurements from the human lens cortex with age. AB - Light scatter and width measurements of the anterior cortical layers of the human lens were made in 50 eyes of 50 subjects using computerised linear scanning densitometry of Scheimpflug images. It was demonstrated that the amount of light scatter increased with age in all of the three major zones and that zone C3 showed the most marked increase. Most lens growth occurs in zone C2 with C3 showing little increase in width once it has become established. Zone C1 showed a tendency to decrease in width with age. In addition it was shown that the C3 zone, which is not present at birth and during early childhood, appears as a distinct layer during the second decade of life. Its scattering properties continue to increase throughout life, exceeding all other zones after approximately 30 years of age, in the absence of cataract. Possible explanations for the lens zone pattern are discussed. PMID- 1426402 TI - Clinical comparison of automated and manual keratometry in pre-operative ocular biometry. AB - Corneal measurements, using the manual (Topcon OM-4) and automated (Canon RK-1) keratometers was performed on 104 eyes of 104 patients undergoing cataract and implant surgery to assess the role of automated keratometry in pre-operative ocular biometry. Four eyes of four patients were excluded from statistical analyses for various reasons. The time taken to perform automated keratometry was a mean of 61 (SD 21) seconds compared to 205 (SD 37) seconds for manual keratometry; the difference was statistically significant (p < 0.001). In terms of the various keratometry values compared, mean K (corneal refractive power), flattest K, steepest K, astigmatism and the axis of astigmatism, 65% to 75% of the cases on automated keratometry were within 0.26 dioptres or 11 degrees of manually determined values; the difference was statistically significant (p < 0.001). Although automated keratometry was significantly quicker than manual keratometry, we continue to use manual keratometry values for intraocular lens power calculations as the accuracy demonstrated by automated keratometry was considered inadequate for this purpose. PMID- 1426403 TI - Keratometry and post-operative astigmatism. AB - Total post-operative refractive astigmatism and keratometric corneal astigmatism were determined in patients following cataract surgery. By comparing the results of the two methods, the value of keratometry as a simple and quick procedure for identification of surgically induced astigmatic errors was established. It is proposed that this method should be used before final refraction in an attempt to increase clinic efficiency and reduce further appointments resulting from surgically induced astigmatism. PMID- 1426404 TI - Diabetes mellitus and retinal vein occlusion in patients of Asian, west Indian and white European origin. AB - The incidence of retinal vein occlusion (RVO) is known to be related to several cardiovascular risk factors including diabetes mellitus, hypertension and hyperlipidaemia. We have assessed the prevalence of these risk factors in Caucasian (N = 536, mean age = 65.21 years), West Indians (N = 24, mean age = 57.3 years) and Asian (N = 28, mean age = 51.4 years) patients presenting with RVO. We found no significant differences between the three groups in the distribution of hyperlipidaemia, but diabetes mellitus was more common amongst both the Asians and W. Indians (10% v 29% and 38%, p < 0.01 and p < 0.001). Hypertension was also more common in both the Asians and the West Indians (59% v 64% and 83% m p < 0.001 and p < 0.0001). The Asians and West Indians presenting with RVO were significantly younger and had significantly higher body mass index than their Caucasian counterparts (Ethnic origin, BMI, mean age: Asian, 28.1 +/- 4.3, 51.5 +/- 12.3 years; West indian: 30.2 +/- 7.7, 57.3 + 10 years; White: 24.8 +/- 4.2, 65.2 +/- 11.4 years). In this study RVO occurred at a younger age in Asians and West Indians, and was associated with a greater prevalence of diabetes mellitus and hypertension. The prevalence of hyperlipidaemia was no different in the three groups. PMID- 1426405 TI - Mathematical modelling of retinal tear formation: implications for the use of heavy liquids. AB - When force is applied to detached retina it elevates, stretches, and becomes irreversibly deformed. Finally it tears, and the timing and location of tear formation are determined by the distribution of stress within the retina. This stress distribution is dependent upon the retinal contour. We have tested this using retinas of freshly enucleated bovine eyes. A suture was attached to isolated retinal tissue using butylacrylate (Histoacryl) glue and traction was applied to this suture so stretching the retina. We present a mathematical model of the in vitro data obtained, with predictions for local retinal internal tensions. We show that these are altered by the addition of hydrostatic forces due to the presence of heavy liquids. These findings have implications for epiretinal membrane dissection during surgery and for the use of heavy liquids during membrane peeling. PMID- 1426406 TI - Genetic counselling in X-linked ocular albinism: clinical features of the carrier state. AB - Forty-nine obligate heterozygotes and 64 at risk females were assessed from 17 families affected by X-linked ocular albinism to determine the relative values of clinical examination and skin biopsy in carrier detection. 92% of obligate heterozygotes had a mud-splattered appearance of the fundus with hyperpigmented streaks and in 74% this was associated with marked iris translucency. Skin histology showed macromelanosomes in 84%. 27 of 64 (42%) at risk females had definite features of the carrier state and 19 (30%) were unequivocally normal but a further 18 (28%) had mild RPE abnormalities, often with iris transillumination defects, of uncertain significance. Fundus examination will detect most carrier females but will not allow reliable genetic counselling for all at risk females, even when supplemented by skin biopsy. PMID- 1426407 TI - Echographic diagnosis of advanced Coats' disease. AB - Standardised echography was utilised to diagnose two cases of advanced Coats' disease. The characteristic acoustic features included extensive, poorly mobile retinal detachment; dense, dispersed subretinal opacities; looping of peripheral retina and absence of solid mass lesion and calcification. As enucleation of two eyes was necessary, it has proved possible to correlate the echographic and histological findings of this disease. The echographic features of other common causes of leukocoria are also discussed. PMID- 1426408 TI - Ophthalmic consequences of mid-facial trauma. AB - Fractures of the mid-face are commonly accompanied by injury to the visual system. Three hundred and sixty three patients who had sustained mid-facial fractures were assessed prospectively for evidence of such injury. The data have been used to devise a scoring system for the maxillofacial surgeon in order to help identify those patients at risk of eye injury. The scoring system has been evaluated on a further cohort of 100 patients with a similar spectrum of injury and the sensitivity and specificity of the system have been determined. The results of these studies have been reported in the maxillofacial literature. This paper reviews the data and results obtained. In summary, impaired visual acuity with a comminuted or out blow fracture, a motility abnormality, or facial fracture combined with head injury, sufficient to cause both retrograde and post traumatic amnesia, emerged as major risk factors which are indicative of an adverse ophthalmic outcome deemed to warrant referral. The scoring system which was developed from this data was found to have a sensitivity of 94.4% and a specificity of 89% for the detection of patients thought to merit ophthalmic assessment. Failure to assess central visual function as objectively as practicable in patients who have sustained mid-facial fractures may lead to potentially treatable ophthalmic pathology not being identified. PMID- 1426409 TI - Choroid plexus papilloma. A new presentation of von Hippel-Lindau (VHL) disease. AB - A definite association between Von Hippel-Lindau [VHL] disease and choroid plexus tumour has not been described previously. A 24-year-old patient was found to have a choroid plexus tumour in the left cerebellopontine angle and involving the temporal bone. Examination of her fundi revealed bilateral retinal angiomatosis, thus making a diagnosis of von Hippel-Lindau disease. Later, an abdominal scan showed renal and pancreatic cysts. An important point is that molecular analysis of the choroid plexus tumour tissue showed chromosome 3 allele loss as described for other tumour types associated with von Hippel-Lindau disease. PMID- 1426411 TI - Pyogenic granulomas of the lacrimal sac. AB - Eight cases of pyogenic granulomas of the lacrimal sac are reported. The clinical symptoms were consistent with chronic dacryocystitis which was unresponsive to previous probing and antibiotics. Extirpation of the sacs was done because of dacryocystocoele, pyocoele, or fistula formation through the skin. Trauma and inflammation were thought to have contributed to the growth of the pyogenic granulomas. The histopathological examination revealed nonspecific granulomas consisting of well vascularised, friable tissue of a myxomatous nature containing an infiltration of lymphocytes, plasma cells, and a few eosinophils. Over the granulomas an epithelial layer of cells is stretched showing no signs of dysplasia or neoplastic growth. The term 'lobular capillary hemangioma' has been suggested to describe lesions morphologically similar to those observed in the study. These masses made up 53.3% of a total of 15 lacrimal sac tumour biopsy specimens examined over a period of 10 years (1979-1989). The few reported cases of primary lacrimal sac tumour of non-epithelial origin suggest that they make up a large minority of the lacrimal sac tumours. A review shows that relatively few of these lesions have been described in recent English literature but these growths are probably not being as consistently reported as primary epithelial tumours. PMID- 1426410 TI - Quantification of the ocular reactions to microfilaricides in the chemotherapy of onchocerciasis. AB - Severe adverse systemic and ocular reactions have complicated the chemotherapy of onchocerciasis. A method for the quantification of ocular reactions to chemotherapy has been devised at the Onchocerciasis Chemotherapy Research Centre, at Hohoe, in Ghana. Symptoms, visual function, anterior segment inflammation and disease of the posterior segment are graded. The information is entered into a computerised database which allows reaction scores to be calculated both for individual patients, and for treatment groups. This system enables comparison of adverse ocular reactions to various new chemotherapeutic regimens. PMID- 1426412 TI - Relationships between the immune system and other physiological functions of the organism. PMID- 1426413 TI - Interleukin 2 and cancer. PMID- 1426414 TI - Immunology and immunopathology of reproduction. AB - This review is dealing with the roles of the immune system in the development and functions of the male and female reproductive systems. Further, it describes the topical views on the roles of immunopathologic events and mechanisms involved in the male and female infertility, recurrent abortions, endometriosis, EPH gestosis and disorders of fetal development. Particular attention is paid to the complicated immunological cross-talk and interplay between the mother and its offspring, including the active role played by the placenta and mainly the trophoblast tissue, in the course of gestation. In the light of the "immunotrophic theory", maternal immune responses to foreign fetal components, occurring in normal pregnancies, within the limits of "tolerated" or even beneficial levels, are described. Emphasis is given on the possible deregulation of materno-fetal immunological balance, leading to immunopathological events and putting in danger the overall reproductive capacity of the couple. The contemporary therapeutic--mainly immunological--approaches to the main reproductive failures are also mentioned. PMID- 1426415 TI - Infection and immunity. PMID- 1426417 TI - Immunopathogenesis of mycobacterial diseases. PMID- 1426416 TI - Autoimmunity: from physiology to pathology. Natural antibodies, mucosal immunity and development of B cell repertoire. AB - Presence of spontaneously produced immunoglobulins bearing a broad spectrum of "natural" antibody specificities (including autoantibodies) in sera and other body fluids results mainly from inapparent immunization and polyclonal B cell activation by microflora and food antigens occurring mostly on mucosal surfaces. Early postnatal ontogeny in external environment is characterized by rapid growth and functional maturation of secondary lymphatic tissues as a consequence of this "natural" mucosal immunization. Under normal circumstances a state of "oral" tolerance to intestinal antigens is actively established after this period. Studies performed in germ-free, antigen-free and maternal antibody-deprived animals showed that low amounts of natural antibodies (mainly of IgM isotype) are formed without any known cause of stimulation. These "nonstimulated" antibodies, similarly as hybridomas originating from nonimmunized newborns, correspond to the preimmune repertoire of antibodies characterized by poly-specificity, high connectivity and reactivity against self antigens. Together with other innate humoral and cellular factors, they probably represent the first line of anti infectious resistance. Moreover, due to their connectivity they are supposed to play an important role in B cell repertoire shaping (forming an idiotypic network), through interaction with a broad spectrum of immunological components they act as regulatory molecules, and through their participation in catabolic events they can promote morphogenetic changes during fetal development. Beneficial therapeutic effects of nonspecific gammaglobulin (IVIG) application observed recently in patients with autoimmune diseases suggest that they can influence autoimmune reactivity by a not yet analyzed mechanism. Other functions of natural autoantibodies can be suggested and expected to be found in the near future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426418 TI - Molecular methods in immunology. PMID- 1426419 TI - IL-1 and pro-inflammatory cytokines produced by primary and transformed fibroblasts abrogate the tumorigenic potential of fibrosarcomas. AB - In the present study we report on novel immunoregulatory functions lately attributed to fibroblasts, namely participation in cellular immune responses in connective tissues, by generation of pro-inflammatory cytokines and by presenting antigens to proliferating T cells. In order to execute immunoregulatory functions, the fibroblast has to be activated by signals abundant at inflammatory sites, i.e., cytokines and bacterial products. It was demonstrated that such immune-activated fibroblasts are able to generate a variety of cytokines such as interleukin-1 (IL-1), IL-6, colony stimulating factors (CSFs) as well as prostaglandins. The array of cytokines generated by immune-activated fibroblasts is determined by the stimulant and is controlled at multiple regulatory levels, such as transcription, translation, post-translational modifications, compartmentalization within the producing cell as well as the timing of expression. Some oncogene-transformed fibroblastoid cells lines were shown to constitutively generate IL-1 (and not IL-1 beta), as evidenced by the continuous expression of specific mRNA and biological activity of the cytokine, associated to the cell membrane or located in the cytosol. When these IL-2 producing cell lines were injected into mice, they failed to generate established tumors or regressed following initial growth, possibly due to mounting the host anti-tumor specific immune responses in which cytotoxic lymphocytes (CTLs) predominate. In contrast, IL-1 non-producing tumor cell lines induced progressive tumors which ultimately killed the animals. However, IL-1 non-producing fibroblastoid cell lines shifted from an in vivo progressive to a regressive phenotype, following immune activation of the malignant cells in vitro with cytokines/LPS. Similarly, primary immune-activated fibroblasts also induced tumor regression, mediated by anti-tumor specific immune responses, when the fibroblasts were injected into the vicinity of the tumor. Thus, the importance of activated stromal cells on tumor development was emphasized. This situation is relevant to the development of malignancies, as tumor growth is often accompanied by a local inflammatory response. Thus, the induction of IL-1 and other pro-inflammatory cytokines expression by the malignant cells or by stromal cells, in the vicinity of the tumor, might be efficient for tumor eradication. These findings should serve as a basis for development of novel immunotherapeutical strategies for the eradication of solid tumors. PMID- 1426420 TI - H-2 influence on ankylosing enthesopathy of the ankle (ANKENT). AB - Joint disease, ankylosing enthesopathy (ANKENT) of the ankle, occurs naturally in mice. ANKENT depends on the genetical constitution, sex, and age, and its frequency varies among inbred strains of normal mice. We found the highest frequency of ANKENT in B10.BR (H-2k) males. The H-2k haplotype appears to be a relative risk factor, which increases the susceptibility to ANKENT. The aetiology of ANKENT is unknown but an involvement of microbial agents in the environment is supposed. PMID- 1426421 TI - Elevated IgA salivary antibody levels to mycobacterial 65 kDa stress protein in patients with oral candidosis. AB - Salivary IgA antibody levels to cytoplasmic protein extract of Candida albicans (CSE) and to mycobacterial 65 kDa stress protein (mSP65) were determined by ELISA in 25 patients with chronic atrophic oral candidosis and in 23 controls with clinically healthy oral mucosa. The results showed significantly elevated anti CSE and anti-mSP65 antibody levels in patients when compared with healthy controls (P < 0.001). A statistically significant relationship was found between salivary antibody titres to CSE but not to mSP65 and C. albicans colony counts in patients with oral candidosis. PMID- 1426422 TI - Childhood typhoid fever diagnosed in an urban U.S. setting. AB - The majority of cases of childhood typhoid fever diagnosed in the United States occur in persons recently returned from travel abroad. We report two childhood cases of typhoid fever acquired in Mexico and India and diagnosed in an urban United States setting. This report describes these cases and provides insights into the pitfalls in recognizing this condition in a nonendemic setting as well as information concerning differential diagnosis and treatment. PMID- 1426423 TI - Cesarean section in a severely traumatized patient. AB - Massive trauma in a near-term pregnant patient challenges the emergency physician with very difficult treatment choices. We present the case of a severely traumatized pregnant female, near term, in whom the decision to proceed with a perimortem cesarean section in the Emergency Department produced a viable infant. We discuss the guidelines that are used in making such a decision and their rationale. The physiologic changes of pregnancy that may complicate maternal assessment and the effect of shock on the fetus are also discussed. PMID- 1426424 TI - Mammography of Delaware van reaches out. PMID- 1426425 TI - 1992 annual meeting of the AMA House of Delegates. PMID- 1426426 TI - HIV in women in Delaware. PMID- 1426427 TI - Summary of health-related legislation. 136th General Assembly. PMID- 1426428 TI - Medical Society of Delaware Mini-Internship Program. PMID- 1426429 TI - Blood donors more likely to reveal HIV risks to computer. PMID- 1426430 TI - NIH Consensus Development Conference on melanoma. PMID- 1426431 TI - Census adjustment and the distribution of federal spending. AB - In 1989, programs that use population counts to determine the distribution of their funds transferred $236 per capita to state and local governments. If the 1990 census were adjusted to reflect undercounting, about 40% of state and local governments would receive increased grants averaging $56 per miscounted person; other jurisdictions would lose an almost equal amount of grant money. The surprisingly small reallocations arise because 1) total funds allocated by population are essentially fixed; 2) allocations depend on other factors in addition to population; and 3) programs vary as to whether they allocate funds in direct or inverse proportion to population. PMID- 1426432 TI - Age of entry into marriage and the date of the initiation of voluntary birth control. AB - It is widely known that modern economic development has been accompanied by the initiation and spread of effective limitation of fertility, and that generally the populations which experienced development at a late date also had a belated reduction in childbearing. Here a surprising relation is found between (and within) broad regions: the areas in which traditional age of entry into marriage was late were the areas in which marital fertility was reduced first. PMID- 1426433 TI - A simple measure of fertility control. AB - We describe a simple measure of fertility control: the proportion of all births from the age-specific fertility schedule that occurs among women by age 35. This measure has broad applicability because it does not require information on marital fertility rates. When both the proportion of births by age 35 and the most commonly used measure of fertility control, m, are calculated for a population over time, they are correlated very highly. Because of increasing levels of nonmarital fertility in several developed countries, measures of fertility control that are based on marital fertility are less appropriate now than in the past. PMID- 1426434 TI - The relationship between cohabitation and divorce: selectivity or causal influence? AB - Recent evidence linking premarital cohabitation to high rates of divorce poses a complex theoretical and empirical puzzle. We develop hypotheses predicting that premarital cohabitation is selective of those who are prone to divorce as well as hypotheses predicting that the experience of premarital cohabitation produces attitudes and values which increase the probability of divorce. Using multiwave panel data from a recent cohort of young men and women in the United States, we specify and test models of these predictions. The results are consistent with hypotheses suggesting that cohabitation is selective of men and women who are less committed to marriage and more approving of divorce. The results also are consistent with the conclusion that cohabiting experiences significantly increase young people's acceptance of divorce. PMID- 1426435 TI - Feathered nest/gilded cage: parental income and leaving home in the transition to adulthood. AB - The growing study of leaving home in young adulthood in the United States has been hampered by data and measurement problems, which are producing a major theoretical confusion about the role of parental resources in influencing young adults' leaving home. Does high parental income retain young adults in the home or subsidize their leaving (and parental privacy)? This paper uses the 1984 panel of Survey of Income and Program Participation to clarify this issue, and shows that the effects of parental resources differ depending on the route out of the home under consideration (marriage or premarital residential independence). Effects change substantially over the nest-leaving ages, but relatively few differences are found between young men and young women. PMID- 1426436 TI - The effects of child health on marital status and family structure. AB - The purpose of this paper is to provide evidence on the effect of child health on marital stability and family structure in an economic framework. We use the 1988 National Health Interview Survey's Child Health Supplement, with a sample of about 9,000 families, to test whether having an unhealthy child decreases the mother's chance of being married and whether it increases her chance of living in an extended family. Using two different measures of child health, we find that having an unhealthy child decreases the mother's likelihood of being married. Our results imply that children in poor health are more likely to face obstacles beyond their illness because they also are more likely to suffer the consequences of poverty and the poor schooling outcomes that result from being raised in a female-headed household. The only mitigating factor is that unhealthy white children are more likely than their healthy counterparts to be living in an extended family. PMID- 1426437 TI - Drug use as a risk factor for premarital teen pregnancy and abortion in a national sample of young white women. AB - The relationship between adolescent drug use and premarital teen pregnancy and abortion as a pregnancy outcome among sexually active women is investigated in a sample of white women from the National Longitudinal Survey of Youth. Event history analysis is used to explore whether prior drug use has a unique effect on premarital teen pregnancy, with controls for personality, lifestyle, and biological factors. Logistic regression is used to estimate whether drug use affects the decision to terminate a premarital teen pregnancy. The results show that the risk of premarital teen pregnancy is nearly four times as high for those who have used illicit drugs other than marijuana as for those with no history of any prior substance involvement. Furthermore, illicit drug use increases the likelihood of an abortion by a factor of 5. Policy implications of the findings are discussed. PMID- 1426439 TI - Residential preferences and residential choices in a multiethnic context. AB - A study of the expressed preferences of four different ethnic groups in the Los Angeles metropolitan area shows strong desires for own-race combinations in the ethnicity of neighborhoods that individuals say they would choose when seeking a new residence. The results also show that Anglos are not the only group to practice "avoidance" of other racial/ethnic neighborhoods, although avoidance behavior by Anglos is the strongest. Because the issues of racial composition are socially sensitive, additional tests examined the relationship of preferences to behavior. Although many behaviors generally follow expressed preferences, members of households who expressed "no preference" also were found to largely choose own race neighborhoods. The results of this study suggest that the expressed preference for own race/own ethnicity, in combination with short-distance local moves, is likely to maintain present patterns of separation in U.S. metropolitan areas. PMID- 1426438 TI - Why are teenagers in the United States less likely to breast-feed than older women? AB - Teenage mothers are much less likely than older mothers to breastfeed their infants. The lower breastfeeding rate among teenagers aged 16-19, compared with women aged 20-29, is due almost entirely to the fact that teenage mothers tend to have characteristics associated with a lower likelihood of breastfeeding among all women, such as lower educational level, lower income, and being unmarried. Even so, nearly 40% of the difference between teenage mothers aged 15 or less and mothers aged 20-29 remains unexplained by these factors and may be due to developmental aspects of adolescence, such as greater egocentricity and greater concern about body image. PMID- 1426440 TI - [Internal live stain. A coloring technique with deep effects]. PMID- 1426441 TI - [Dicor Plus. New aspects of full ceramic]. PMID- 1426442 TI - [Implant supported restorations using the Calcitec system]. PMID- 1426443 TI - [Documentation of case with conical crowns and no construction errors]. PMID- 1426444 TI - [Structure formation of the In-Ceram core material]. PMID- 1426445 TI - [Hawley plate for normalization of muscle function]. PMID- 1426446 TI - [Irregularity is everything. Aspects of individual combination techniques]. PMID- 1426447 TI - [Patient's smile is a criterion for esthetics and harmony]. PMID- 1426449 TI - [Cold-plate-system. Ceramic materials remain dewy fresh]. PMID- 1426448 TI - [Part 2. Adhesive systems for dentistry and dental technique. Adhesives and adhesive techniques]. PMID- 1426450 TI - [Disturbed field tooth--covert energy stealer and disease cause]. PMID- 1426451 TI - [Esthetics and function. Solution to a patient case]. PMID- 1426452 TI - [Crucible material for smelting noble metal dental alloys]. PMID- 1426453 TI - [Objective tooth color determination. Error source elimination]. PMID- 1426454 TI - [Immenkamp inactivator plate and Schulte interceptor]. PMID- 1426456 TI - Reform the health-insurance industry. PMID- 1426455 TI - [Hydra active. Laboratory organization software]. PMID- 1426458 TI - Dentists rise above nation's economic woes. PMID- 1426457 TI - Mandatory testing? PMID- 1426459 TI - Only a dentist. PMID- 1426460 TI - Getting from here to there. PMID- 1426461 TI - Monitor your practice. PMID- 1426462 TI - Doctor gets 'lift' from office remake. PMID- 1426463 TI - Want a thriving practice? Concentrate on clinical excellence. PMID- 1426464 TI - Closing a large central diastema. PMID- 1426465 TI - Site specific chemotherapy in periodontal management: an exciting new direction. PMID- 1426466 TI - The advantages of the flexi-model technique to produce superior anterior restorations. PMID- 1426467 TI - The lab as a customer. PMID- 1426468 TI - Who is in charge? PMID- 1426469 TI - Are you referring to me? PMID- 1426471 TI - Designed for team practice. PMID- 1426470 TI - Building your practice to sell. PMID- 1426472 TI - Who's hurting whom. PMID- 1426473 TI - Do you need a larger staff? PMID- 1426474 TI - Computer systems review. PMID- 1426475 TI - The dental computer: a powerful marketing tool. PMID- 1426476 TI - Making the right decision. PMID- 1426478 TI - Rising to success. PMID- 1426479 TI - Working with consultants. PMID- 1426477 TI - Unexpected doesn't mean unprepared. PMID- 1426480 TI - Clinic designed for two practices. PMID- 1426481 TI - Simplified pensions! PMID- 1426483 TI - Avoid pitfalls when renewing your lease. PMID- 1426482 TI - Enjoy the silver age of dentistry. PMID- 1426484 TI - It could happen to you. PMID- 1426485 TI - Communicating infection control to patients. PMID- 1426486 TI - He puts teeth in his words. PMID- 1426487 TI - Marketing bleaching services. PMID- 1426488 TI - Product resource file. Cements. PMID- 1426489 TI - Immunogenetic and evolutionary influences on the host-parasite relationship. AB - Immunogenetic aspects of the host-parasite relationship between the laboratory mouse and the parasitic nematode Trichinella spiralis are reviewed. Variation in the capacity of hosts to express an effective protective immunity is associated primarily with variation in inflammatory responsiveness. Analysis of the contributions of T lymphocytes, cytokines, and myeloid precursor populations to variation in one particular inflammatory component, eosinophilia, is described. Variation in parasite immunogenicity at the level of host responsiveness to different parasite isolates is described briefly. Variations in host-protective immunity, immunopathology, and parasite immunogenicity are discussed in terms of evolutionary pressures selecting for optimal host and parasite survival in a stable symbiosis. PMID- 1426490 TI - Function associated molecules on nonspecific cytotoxic cells: role in calcium signaling, redirected lysis, and modulation of cytotoxicity. AB - Monoclonal antibodies (mAbs) specific for a putative antigen receptor (function associated molecule, FAM) on fish NCC were tested for their ability to initiate signal transduction responses. Anti-FAM hybridoma target cells were significantly lysed by NCC when tested by redirected lysis (RL). Redirected lysis was enhanced by 1-h pretreatment of the NCC with anti-FAM mAb; however, 18-h pretreatment produced significant inhibition. The effects of the calcium ionophore A23187 on RL were also examined: 10(-4) M but not 10(-5) M A23187 significantly increased RL. Purified NCC were treated with mAb and cellular DNA synthesis was determined. Significant increases in NCC incorporation of tritiated thymidine were measured 72 h after treatment with mAb. Experiments were also conducted to determine levels of free cytosolic calcium in NCC following mAb binding. Anti-FAM mAb binding produced a rapid rise in cytosolic calcium (200-500 nM) determined by Fura-2/AM fluorescence. Calcium ionophore A23187, PHA, and Con-A treatment of NCC also produced significantly increased [Ca2+]i. Target cell binding by NCC caused a three-fold increase in [Ca2+]i. These data suggest that triggering of the FAM may initiate a signal(s) that activates cytotoxicity, increases cytosolic free calcium concentrations, and initiates DNA synthesis. PMID- 1426491 TI - A species-conserved NK cell antigen receptor is a novel vimentin-like molecule. AB - The role of a novel, evolutionarily conserved function-associated molecule (FAM) in NK cell function has been examined in several species. This molecule has previously been shown to mediate NK and NK-like recognition functions in fish NCC and human NK cells. We now show that this molecule is distributed in those tissues that contain NK cells in mice and rats. Further, we show that this molecule functions as an antigen receptor on NK cells of these species. That is, monoclonal antibodies directed against this FAM inhibit NK cell cytotoxic function and trigger signal transduction pathways in each of the species. Finally, we present evidence that this putative antigen receptor is a vimentin like molecule which functions to mediate all NK or NK-like recognition functions in a variety of species. PMID- 1426492 TI - NADPH oxidase-like activity in rainbow trout Oncorhynchus mykiss (Walbaum) macrophages. AB - Evidence for the existence of an NADPH oxidase-like enzyme in rainbow trout macrophages is given. Reduced-minus-oxidised difference spectroscopy revealed the presence of a cytochrome b with three absorbance peaks, at 430, 533, and 558 nm. The low midpoint potential of the latter peak suggests this cytochrome is the same as the terminal component of NADPH oxidase (i.e., cytochrome b-245). Subcellular fractionation of macrophages revealed two peaks of cytochrome b activity, in accord with the concept of a plasma membrane localisation of cytochrome b activity in addition to a mitochondrial localisation. Finally, that the rainbow trout oxidase is a multicomponent enzyme was suggested by inhibitor studies, where specific inhibitors of the flavin and cytochrome b-245 components of NADPH oxidase induced significant reduction in superoxide anion production. PMID- 1426493 TI - A peculiar immunoglobulin M (IgM) identified in eggs of chum salmon (Oncorhynchus keta). AB - A protein reacting with antibody against chum salmon serum IgM was found in salmon egg yolk. The protein tentatively named IgM-like protein was partially purified from egg yolk extract by removal of euglobulin from the extract by dialysis against a low ionic strength buffer following DEAE ion-exchange chromatography. The IgM-like protein was antigenically identical with serum IgM, showing a complete fusion of precipitin line of the IgM-like protein with that of serum IgM on double immunodiffusion with antiserum IgM. The molecular weight of intact IgM-like protein was assessed by 3% SDS-PAGE to be 495 kDa, smaller than that of serum IgM (750 kDa). Upon 10% SDS-PAGE with mercaptane and subsequent Western blotting with antiserum IgM, the IgM-like protein separated into three components with molecular weights of 68 kDa, 51.5 kDa, and 23 kDa. The 68 kDa, the most minor component, and the 23 kDa, the smallest molecular weight component, were identified, respectively, as H and L chain in view of their molecular weights identical to those of serum IgM. The 51.5 kDa, the main component, was also identified as H chain, since it reacted with antiserum IgM absorbed with purified L chain. From these results, it was concluded that the IgM like protein in egg yolk, having a lower molecular weight than that of serum IgM, consists of H chain of smaller molecular weight as well as H and L chain of ordinary molecular weight. PMID- 1426494 TI - Correlation of subjective assessment of amniotic fluid with amniotic fluid index. AB - We assessed the correlation between abnormal amniotic fluid volumes as defined by the two techniques of (1) subjective evaluation and (2) the amniotic fluid index. Ultrasound evaluation of amniotic fluid volume was conducted on 420 pregnant women with known gestational age greater than twenty weeks but less than 42 weeks. Amniotic fluid was evaluated subjectively and placed into one of three categories: normal, oligohydramnios or polyhydramnios. After fetal biometry was performed, the amniotic fluid volume was assessed semi-quantitatively by the amniotic fluid index technique and assigned to similar categories. We analyzed the data with 2 x 2 contingency tables, using amniotic fluid index as the 'gold standard test'. Our study demonstrates that there was moderate agreement (kappa.5) between both amniotic fluid techniques in the identification of oligohydramnios. However, agreement between the techniques was poor for the identification of polyhydramnios (kappa.16). PMID- 1426495 TI - Atrial natriuretic peptide (ANP) and N-terminal peptide of proANP (NT-proANP) in maternal and umbilical cord plasma in spontaneous labor and at elective cesarean section. PMID- 1426496 TI - Loss of PAF-like activity from human embryo conditioned media (ECM) following HPLC separation. AB - Recently a platelet activating factor (PAF)-like activity has been found in embryo conditioned media (ECM) and consequentially been termed embryo-derived PAF (EPAF). Yet it remains unclear whether the embryo-released molecule is in fact PAF or a PAF precursor or inductor in vivo. In this study we shall show that ECM did not induce platelet aggregation in vitro; however, it was possible to detect PAF-activity using the sensitive splenectomized mouse bioassay (SMB). Following lipid extraction, PAF activity was diminished, and after additional HPLC separation completely lost. We propose that the active fraction of ECM is lipid in nature but that this molecule is not PAF. We would rather suggest that this molecule induces the production of PAF by other cell types in vivo. PMID- 1426497 TI - Conservative management of placental abruption complicated by severe clotting disorders. AB - Placental abruption resulting in fetal death may seriously affect maternal health, especially when clotting disorders arise. The prevailing view is that the clotting system will only normalize after the uterus has been evacuated and therefore prompt delivery, often by induction of labor, is advocated. Over a 3 year period, 16 cases (0.35%) of intra-uterine fetal death due to placental abruption occurred at Leiden University Hospital. Five cases were complicated by severe clotting disorders. All women delivered vaginally. No maternal deaths occurred. In contrast to most authors, we present data showing that in four out of five cases the clotting system started to normalize before the uterus was emptied. We suggest that an expectant approach until recovery of the coagulopathy is safer than aiming at a quick delivery. After stabilization of the clotting disorder, one may then consider evacuation of the uterus, if need be by induction of labor. PMID- 1426498 TI - Hysteroscopic diagnosis of ectopic pregnancy. AB - Although vaginal ultrasonography combined with plasma beta-hCG determination can provide a reliable diagnosis and location of ectopic pregnancy, the results can be difficult to interpret in the early stages when hCG levels are low. Hysteroscopy can be used in such cases to differentiate between ectopic pregnancy and non-viable uterine pregnancy when viable uterine pregnancy has been ruled out. General anaesthesia and laparoscopy are avoided. We performed 60 hysteroscopic procedures between January 1989 and December 1990 in patients with suspected ectopic pregnancies. The pregnancy had been located by means of vaginal ultrasonography in every case in which the hCG was above 1500 IU/ml and in 36% of cases in which the beta-hCG was below this level. Hysteroscopy was hindered by metrorrhagia in three cases and was inconclusive in one, necessitating laparoscopy. Diagnosis was possible in all the remaining cases, as follows: ectopic pregnancy in 41 cases, with an empty uterus and occasional bleeding from an ostium; non-viable uterine pregnancy in 18 cases, with the presence of material within the cavity. Hysteroscopy therefore confirmed the diagnosis in 55% of the cases and was itself diagnostic in a further 43% of cases. Its sensitivity for the diagnosis of ectopic pregnancy was 100% and its specificity 95%. We propose a diagnostic decision tree. PMID- 1426499 TI - Vaginal progesterone as luteal phase support in an IVF/GIFT programme. AB - To determine whether luteal phase support with vaginal progesterone could improve pregnancy rates in our IVF/GIFT programme, we performed a prospective randomised controlled study. After stimulation with clomiphene citrate/human menopausal gonadotrophin, 123 women received no luteal support and 122 received progesterone pessaries 100 mg b.d. from 48 hours prior to embryo transfer and continued throughout the luteal phase. There was no difference in the pregnancy rate following IVF/ET (6/58 and 10/58 for the pessary and control group respectively), but a significantly higher rate was noted for GIFT (13/34 and 5/42 for the pessary and control group respectively; P less than 0.05). Of interest, only one of the 19 pregnancies using luteal support was extra-uterine, compared with 6/15 in the control group. PMID- 1426500 TI - Platelet-activating factor levels in human follicular and amniotic fluids. AB - Platelet-activating factor (PAF) was estimated in extracts of human follicular and amniotic fluids using a commercially available 125I-radioimmunoassay. Levels obtained before and after purification of the extracts by thin-layer chromatography were similar and PAF could be estimated with high accuracy and reproducibility over a wide dilution range. PAF levels in fluid aspirated from mature (17 mm average diameter) follicles from in vitro fertilization patients were 1005 +/- 129 fmol/ml in successful (clinical pregnancy) cycles and 949 +/- 75 fmol/ml in unsuccessful (failure of implantation) cycles. PAF levels were also similar in follicles containing eggs and those where no egg was found, and in fluid from follicular cysts characterised by low oestradiol and progesterone levels. PAF was detected in midtrimester amniotic fluid (60 +/- 20 fmol/ml). At term, PAF was low or undetectable in amniotic fluid obtained at elective caesarean section before the onset of labour, but increased to 102 +/- 28 fmol/ml in samples obtained following spontaneous labour and vaginal delivery. The data suggest that PAF may be involved in ovulation and parturition but further studies into the mechanism of action of PAF are necessary. The good performance of the radioimmunoassay and the convenience of gamma-counting are strong advantages of this method over the available bioassays, but its expense remains a drawback. PMID- 1426501 TI - Developmental patterns of bioactive and immunoreactive FSH in the female rabbit: effects of ovariectomy. AB - A longitudinal study was performed to determine the relationship between immunoreactive and biologically active FSH in the serum of sham-operated and ovariectomized female rabbits. Twenty-two-day-old female rabbits, 8 per group, were sham-operated or bilaterally ovariectomized on day 23. Blood was taken every 3-4 days from each rabbit until they achieved a weight of 3 kg or age 100 days. Sera were analysed by radioimmunoassay for LH and FSH or for bioactive FSH. In sham-operated animals, immuno-FSH levels showed a 10-fold increase from 0.36 +/- 0.04 ng/ml to greater than 35 ng/ml between days 45 and 80. By contrast, bio-FSH levels increased more gradually from a baseline of 5.4 +/- 0.4 ng/ml to about 8 ng/ml. Bilateral ovariectomy resulted in a significant increase in both bio-FSH, 5.5 +/- 0.4 ng/ml to 12.6 +/- 1.5 ng/ml and immuno-FSH levels from 0.4 ng/ml to 5.2 +/- 1.4 ng/ml 24 h later. These levels of FSH remained elevated throughout the sampling period in both groups of animals and then decreased after day 100. Peripheral LH levels showed much more variation but were 2-fold higher in ovariectomized rabbits, 0.4-1.4 ng/ml in sham-operated vs. 0.8-2.4 ng/ml in ovariectomized rabbits. These results emphasize the marked variations in FSH levels according to the method of analysis. They also suggest that extra-ovarian factors may play a role in inhibiting gonadotropin release especially LH. PMID- 1426502 TI - Aspiration of ectopic pregnancy under guidance of vaginal ultrasonography. AB - This case report describes the treatment of tubal pregnancy by aspiration of the gestational sac content and injection of methotrexate by transvaginal sonographic guidance. The confirmation of the embryo aspiration as indicated by disappearance of the embryo with its heart beat and the resulting 46,XY karyotype, raises the question whether methotrexate injection is necessary. PMID- 1426503 TI - Tubal rupture despite low and declining serum hCG levels. PMID- 1426504 TI - Short-term effects of ritodrine, aminophylline and atropine on umbilical artery blood flow velocity waveform. AB - With the recent introduction of Doppler technology, a non-invasive methodology which enables to evaluate qualitative changes in circulatory vessels, it is possible to investigate the possible effects of various drugs on several parameters of utero-placental-fetal circulation. In the present study we evaluate the flow velocity waveform (FVW) of umbilical artery (UA) during and after administration of aminophylline, atropine and ritodrine to healthy pregnant women. In our study we did not observe any significant short-term variation of PI after the administration of these drugs. Slight variations were detected, and they may be interpreted on the basis of the mode of action of these drugs. Doppler technology may be a useful tool for monitoring some effects on the fetus of the maternal administration of therapeutic agents. PMID- 1426505 TI - Gemeprost-induced cervical ripening: histological and biophysical effects. AB - The mechanism of prostaglandin-induced cervical ripening is not clear. The aim of this study was to measure the biophysical and histological effects of gemeprost on the cervix. Thirty-four women admitted for surgical termination of pregnancy in the first trimester were randomised in a double-blind manner to receive either gemeprost or placebo prior to surgery. In 20 (10 active, 10 placebo) a needle biopsy was taken from the anterior lip of the cervix prior to cervical dilatation for histology. The forces required to dilate the cervix from 3 mm to 10 mm were measured. A group of seventeen parous women undergoing surgical termination who did not receive gemeprost were also studied as a parous control group. A needle biopsy was obtained in eight of them and also in six non-pregnant parous women undergoing hysterectomy for benign conditions, the latter acting as a non pregnant control group. Polymerised collagen was stained with Picrosirius red and glycosaminoglycans with alcian blue using a MgCl2 gradient. Optical densitometry was used as an objective measure of staining. Neutrophil concentration was assessed immunohistochemically. Gemeprost treatment increased free passibility (the size of the largest dilator which could be passed without encountering resistance) (P < 0.01), reduced the forces required to dilate the cervix (P < 0.01) reduced blood loss (P < 0.05), reduced the collagen concentration (P < 0.01) and was associated with a modest neutrophil influx (P < 0.02) as compared to placebo. The pregnant parous group had a significantly lower collagen concentration than the non-pregnant parous group (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426506 TI - Intra-amniotic pressures following vaginal gemeprost prior to first and second trimester termination of pregnancy. AB - Intra-amniotic pressures were measured following 1 mg gemeprost for cervical preparation before first trimester vacuum aspiration (n = 10) and following 2 mg gemeprost before second trimester dilatation and evacuation (n = 15). Twenty-five women, matched for gestational age and parity, who did not receive gemeprost served as controls. Compared to control values (2-8 mmHg), basal intra-amniotic pressure (IAP) was significantly increased after 1 mg and 2 mg of gemeprost (median 20.0, range 4-45 mmHg, median 20.0, range 8-60 mmHg, respectively). Uterine contractions were recorded in 8 of 10 subjects after 1 mg (median delta IAP 28.0, 95% CI 10.0-42.6 mmHg) and 14 of 15 subjects after 2 mg (median delta IAP 52.5, 95% CI 26.7-60.3 mmHg). Gemeprost produces an increase in uterine contractility which may be additional to cervical softening properties and which may be responsible for the adverse effects of pain and bleeding experienced by some women prior to termination. PMID- 1426507 TI - Predictive value of pelvic scores for induction of labor by local PGE2. AB - The predictive value of pelvic scores, parity, age and gestational age for induction of labor by local prostaglandin-E2 (PGE2) was examined in 336 women attempting induction of labor by intracervical or vaginal PGE2. The patient characteristics were correlated to: (1) vaginal delivery within 48 h, (2) the period from induction to onset of labor (latency period), and (3) the duration of labor. The Bishop score (P < 0.01) and even more the Lange score (P < 0.0001) were significantly inversely correlated to both latency period and induction delivery period. This was caused by cervical dilatation (P < 0.001), fetal station (P < 0.05) and cervical length (P < 0.05), whereas position and consistency of the cervix were of no importance. All three periods studied were significantly (P < 0.0001) shorter in parous women. In primiparous women, gestational age was of no importance for the latency period; however, higher gestational age was associated with longer labor (P < 0.001). We conclude that the predictive value of pelvic scores on induction hardly differs using local PGE2 compared to conventional methods; furthermore, the Bishop score should be substituted, disregarding position and consistency of the cervix, but putting more weight to cervical dilatation. A new pelvic score is proposed. PMID- 1426508 TI - Impaired 1,25-dihydroxyvitamin D production in pregnancy-induced hypertension. AB - The aim of the study was to evaluate the calcium metabolism in pregnancy-induced hypertension. Fifty-three women with pregnancy-induced hypertension were studied and the control groups comprised 20 women with uncomplicated pregnancies in the third trimester and 51 non-pregnant women, respectively. The mean serum concentrations of 1,25-dihydroxyvitamin D in women with pregnancy-induced hypertension was low (38.6 +/- 21.4 pg/ml) compared to women with uncomplicated pregnancies (91.0 +/- 18.2 pg/ml), but comparable to levels in non-pregnant women (32.2 +/- 11.9 pg/ml). Mean serum levels of PTH and ionized calcium were comparable in women with pregnancy-induced hypertension and women with uncomplicated pregnancies. In conclusion, the calcium metabolism in pregnancy induced hypertension was changed compared to uncomplicated pregnancies with respect to the serum concentration of 1,25-dihydroxyvitamin D. PMID- 1426509 TI - Blood flow velocity in the fetal abdominal aorta and in the umbilical artery in uncomplicated pregnancies. AB - The blood flow velocity waveform (BFWV) in fetal vessels depends on the stroke volume and the frequency of the fetal heart, the compliance of the vessel and the peripheral resistance of the fetal vascular bed. The objective of the present study was to establish the change of the BFVW throughout gestation and whether the change of the resistance indices are related to the peak flow velocity and/or the end-diastolic flow velocity. The BFVW of the fetal abdominal aorta and of the umbilical artery at 27th-30th week and at 37th-40th week of gestation were analysed in fifteen patients with uncomplicated pregnancies and subsequent normal outcome. The measurement was performed with a pulsed duplex scanner (Kranzbuhler). The Doppler beam had a fixed angle of 50 degrees to the fetal vessel in all cases. The peak flow velocity in the fetal aorta remained constant from the 27th-30th week to the 37th-40th week of gestation: 1418 +/- 248 Hz vs. 1448 +/- 269 Hz. The end-diastolic flow, however, showed a significant increase during the respective periods: from 270 +/- 59 Hz to 325 +/- 69 Hz. The peak flow velocity in the umbilical artery was about 25% below that of the fetal aorta: 1028 +/- 149 Hz (27th-30th week) and 1106 +/- 196 Hz (37th-40th week). The end diastolic flow, however, increased by about 41%: 292 +/- 86 Hz vs. 412 +/- 83 Hz demonstrating a tremendous change of the compliance and the peripheral resistance in the umbilical vascular system. These alterations are also exhibited by the resistance indices. The resistance indices S/D, PI and RI of both vessels were related to the EDF of the abdominal aorta and the umbilical artery at the respective gestational age. It demonstrated that the EDF is of major influence on the calculated resistance indices. The blood flow in the aorta and the umbilical artery was 135(+/- 18) ml/kg/min and 143 (+/- 21) ml/kg/min, respectively. In conclusion, the BFVW for fetal surveillance should be measured under a constant angle in the fetal abdominal aorta. It gives a good information concerning the peripheral resistance and compliance in the respective vascular areas. The EDFV has its lowest value at 200 Hz in the fetal aorta and in the umbilical artery under physiological conditions. PMID- 1426510 TI - The relationship between prior cervical conization, cervical microbial colonization and preterm premature rupture of the membranes. AB - The occurrence of prior cervical conization and the cervical microbial colonization was investigated in 38 women with idiopathic preterm labor, 35 women with preterm premature rupture of the membranes (PPROM) and 75 normal pregnant women at 26-34 weeks of gestation. Data were analyzed by Fisher's exact test (two tailed). The frequency of prior cervical conization was significantly higher in PPROM patients compared to normal pregnant women (P < 0.001) and to patients in preterm labor (P < 0.01). Lactobacilli occurred with a lower frequency in patients with PPROM compared to patients in preterm labor (P < 0.05) and control patients (P = 0.0543)-and with a lower frequency in patients with prior cervical conization (P < 0.05). All other microorganisms occurred with the same frequencies in all groups. The absence of lactobacilli may indicate changes in the cervical flora, which could increase the risk of PPROM. Prior cervical conization may impair the antimicrobial defense-mechanisms in the cervix, which could facilitate ascending microbial colonization. This may lead to a release of prostaglandins and proteolytic enzymes and subsequently preterm labor and rupture of the membranes. PMID- 1426511 TI - Pregnancy after fifty: profile and pregnancy outcome in a series of elderly multigravidae. AB - A series of seven women aged 50 years and over was studied over two years to analyse patient profile and pregnancy outcome. All were first-generation immigrant Asian multigravidae who were Muslims of low socio-economic status and who had never used contraception. The median age at booking was 52 (range 51-59 years) and the median parity was nine. One woman had gestational diabetes and one had an antepartum haemorrhage. There were few intrapartum or puerperal problems but an increased rate of Caesarean section (28.6%) was noted. There were no stillbirths, neonatal deaths or congenital anomalies in this series. The mean birth weight was 3.3 kg and the mean gestation at delivery was 39.2 weeks. There was no significant perinatal morbidity. Five of the seven women declined further family planning advice. A possible relationship between race, parity and age at menopause is discussed. PMID- 1426512 TI - Prophylactic oophorectomy. AB - The risks and benefits of prophylactic bilateral oophorectomy (BO) accompanying hysterectomy are reviewed. The potential reduction in the risk of subsequent ovarian cancer is quantified using literature data and a mathematical model. The risks of subsequent breast cancer from low-dose ERT are estimated using a comprehensive mathematical model. It is hypothesized that BO may have a substantial protective effect on breast cancer risk despite subsequent low-dose or non-low-dose ERT, when BO is performed at an early age. In women with a family history of ovarian cancer or breast cancer, the individual risks must be assessed on the basis of a pedigree analysis. In conclusion, a decision on BO must be based on weighing the potential benefits of reduced ovarian and breast cancer risks against the psychological importance of retaining the ovaries and the risk of osteoporosis and cardiovascular disease when compliance with ERT is less than perfect. The provided quantitative data may help in making the right decision. PMID- 1426513 TI - Lack of effect of topical iodostearic acid on cervical intraepithelial neoplasia II-III. AB - Stearic and iodostearic acid inhibit growth of a cervical carcinoma cell line in vitro. This study was performed to determine if iodostearic acid would induce regression of cervical intraepithelial neoplasia (CIN). Women with histologically proven CIN II or III were randomised into two groups. Those in the first group were given pessaries composed of iodostearic acid in polyethylene glycol (PEG) base. Women in the second group were given pessaries containing only the PEG base. One pessary was inserted into the vagina nightly for 30 nights, and each woman then had the CIN lesion removed by CO2 laser cone excision. There was no difference in the histology of the cone biopsies between the groups, demonstrating that this regime of iodostearic acid has no useful role in the treatment of CIN II-III. PMID- 1426514 TI - Management of eclampsia: cardiopulmonary arrest resulting from magnesium sulfate overdose. AB - An eclamptic seizure occurring at 32+2 weeks of gestation was treated with magnesium sulfate. Accidentally an overdose was given. As a consequence, the patient had a cardiopulmonary arrest. Immediate resuscitation and calcium gluconate administration did restore vital functions. Pregnancy continued for 4 weeks after the accident. Both mother and child left the hospital in good condition. PMID- 1426515 TI - Successful delivery after hepatic rupture in previous pre-eclamptic pregnancy. AB - Rupture of the liver in the course of pre-eclamptic pregnancy is a rare but life threatening event. Controversiality exists with regard to the treatment modality. A case is presented of a pre-eclamptic multiparous woman with liver rupture and intra-abdominal bleeding immediately after delivery of a stillborn infant, who was successfully treated by correction of intravascular volume with blood transfusions without surgical intervention. The index pregnancy was succeeded by an uneventful pregnancy and delivery. This is the first case report of a conservatively managed liver rupture with an uneventful course of the next pregnancy. Conservative treatment should consist of correction of hypovolemia and clotting disorders, while surgical approach should be reserved for patients who cannot be stabilized hemodynamically. PMID- 1426516 TI - Fulminant subarachnoidal hemorrhage and coma subsequent to sudden-presenting hypertension. AB - An unusual case of pre-eclampsia is presented, where a previously normotensive primigravida suddenly developed hypertension which evolved to subarachnoidal hemorrhage and coma within minutes. Delivery by cesarean section was followed by progressive and complete recovery in the next few days. PMID- 1426517 TI - Possible relationship between coding recognition amino acid sequence motif or residue(s) and post-translational chemical modification of proteins. AB - 1. The "code-sequence" of N-glycosylation site(s), the amino acids located around O-glycosylation site(s), the sequence motifs of several kinases, the sequence motifs of--sulfation, amidation, isoprenylation, myristoylation, palmitoylation and N-acetylation, Aspartic and Asparagine hydroxylation-site, gamma carboxyglutamate domain, phosphopantetheine attachment site etc. are extensively listed, compared to those reported by "PROSITE" Computer Screen Center and discussed. 2. The structural aspects of protein-DNA recognition are quoted as discussion and conclusion. PMID- 1426518 TI - Chemoprevention of cancer: protease inhibitors. AB - 1. The defense of the organism against cancer by inhibitors of proteolytic enzymes which are able to block the metastasizing stage of the disease is reviewed. 2. The contemporary views on the possible mechanisms of the process of prevention on both molecular and cellular levels are presented. PMID- 1426519 TI - An improved method for the purification of lignin peroxidases from Phanerochaete chrysosporium INA-12: properties of two major isoforms. AB - 1. Phanerochaete chrysosporium INA-12 secretes several lignin peroxidase isoenzymes. This paper reports an improved procedure for the purification of the different isoforms compared to those previously described. 2. Lignin peroxidases are first concentrated and prefractionated on fast-flow ion-exchangers which avoid concentration by ultrafiltration and dialysis. 3. Further purification is achieved by hydrophobic interaction chromatography and anion-exchange FPLC. 4. Two major forms were purified to homogeneity. Kinetic measurements and protein characterization (isoelectric points, phosphate content) suggest that they are similar to those produced by P. chrysosporium BKM strain. PMID- 1426520 TI - Nuclear glycoproteins of hamster liver and Kirkman-Robbins hepatoma recognized by concanavalin A. AB - 1. Glycoproteins recognized by Concanavalin A (ConA) have been identified in nuclei and nuclear fractions differing in sensitivity to micrococcal nuclease digestion from hamster liver and Kirkman-Robbins hepatoma. 2. The major ConA binding proteins from hamster liver and Kirkman-Robbins hepatoma nuclei have molecular weights about 27,000 and 57,000, and 38,000 and 49,000, respectively. 3. A distinct distribution of glycoproteins between fractions differing in sensitivity to nuclease digestion has not been observed. PMID- 1426521 TI - Function of intracellular phospholipase A2 in vectorial transport of apoproteins from ER to Golgi. AB - 1. The cytosolic fraction required in in vitro reconstituted intracellular transport of mucus glycoprotein apopeptide (apomucin) was isolated and its potential as transport supporting factor assessed by the quantitation of the gastric apomucin transferred to Golgi. 2. The experiments with the fraction promoting transport and delivery of apomucin to Golgi revealed that the active protein has the property of phospholipase A2 (PLA2) which assists ER vesicles fusion with Golgi. 3. The ability of the 76 kDa PLA2 to hydrolyze phospholipids and to support transport and fusion of ER vesicles with Golgi was abolished by phosphorylation and regained following dephosphorylation. 4. The data provide evidence that 76 kDa intracellular PLA2 is responsible for the fusion of ER transport vesicles with Golgi. The process of fusion is accomplished by generation of lysophospholipids in fusing membranes. PMID- 1426523 TI - Analysis of the interaction uridin 5'-diphosphoglucuronic acid with intestinal bilirubin UDP-glucuronyltransferase. AB - 1. Bilirubin UDP-glucuronyltransferase Michaelis-Menten kinetic parameters for UDP-glucuronic acid were studied using native and digitonin activated microsomes obtained from rat intestinal mucosa. 2. The intestinal enzyme showed a lower apparent Vmax compared with the hepatic enzyme in both native and activated microsomes; digitonin pretreatment enhanced Vmax 4 times in the former enzyme and 2 times in the latter. 3. The affinity of UDP-glucuronic acid for the intestinal enzyme was about 2 times lower than that for the hepatic enzyme and it was not substantially modified by detergent neither in the intestine nor in the liver. 4. The lipid analysis of intestinal and hepatic microsomes showed that the former present a higher content of cholesterol and a lower phosphatidylcholine/sphingomyelin ratio than the latter, accordingly the estimation of membrane fluidity using the fluorescence anisotropy of 1,6-diphenyl 1,3,5-hexatriene indicated that intestinal microsomes are more "rigid" than the hepatic ones. 5. These characteristics would provoke a restrictive milieu surrounding the enzyme that modifies its kinetic properties thus limiting its participation in the metabolism of bilirubin. PMID- 1426522 TI - Bilirubin production and conjugation from newly formed heme in isolated rat hepatocytes. AB - 1. Heme synthesis from delta-aminolevulinic acid (delta-ALA) in freshly isolated rat hepatocytes was maximal at 100 microM with a rate of approx. 7 nmol being synthesized per g wet weight cells. 2. Approximately 8% of synthesized heme was converted to bilirubin and 50% of the newly synthesized bilirubin was conjugated. 3. The ratio of di to monoconjugate was approx. 2.5. Incorporation of delta-ALA into bilirubin was increased by additional delta-ALA, heme and was also doubled in cells isolated from animals treated with CoCl2. 4. Bilirubin formation was inhibited approx. 90% by in vitro treatment with heme oxygenase inhibitors zinc and tin protoporphyrin. PMID- 1426524 TI - Characterization of the proteins from Melanoplus bivittatus that bind juvenile hormone, and a refined EFDA photolabeling technique. AB - 1. Juvenile hormone (JH) is specifically bound by a protein from hemolymph and fat body cytosol of the grasshopper, Melanoplus bivittatus. 2. This protein has a native molecular weight of 331,000 and subunits of 77,000. 3. Proteins that bind JH were covalently photolabeled with a JH analog, epoxyfarnesyl diazoacetate (EFDA). Samples were irradiated in spot plates and hydroxyapatite was used to separate bound from free [3H]EFDA. Differential solubilization was used to extract unlinked [3H]EFDA and solubilize [3H]EFDA linked to protein. 4. Hemolymph proteins of M(r) 479,000, 240,000 and 77,000 also bound [3H]EFDA. 5. Proteins that bound [3H]EFDA were not vitellogenins. PMID- 1426525 TI - Characterization of Ca(2+)-ATPase of Setaria cervi (Nematoda: Filarioidea): effect of phenothiazines and anthelmintics. AB - 1. A Mg2+ independent, Ca(2+)-ATPase requiring high concentrations of Ca2+ (5 mM) for the activation, equally distributed in cuticle-muscular-hypodermis, genital organs and gastrointestinal tissues and mainly localized in 10,000 g pellet fraction, was identified in Setaria cervi, a bovine filarial parasite. 2. Filarial enzyme showed Km value of 3.33 mM for ATP as computed from the double reciprocal Lineweaver-Burk plot. 3. The enzyme could be completely solubilized by sonication with about 4-fold increase in specific activity of the enzyme. 4. The enzyme showed about 2-fold activation by the calmodulin fractions isolated from S. cervi and rat brain homogenates. 5. The enzyme was highly sensitive to inhibition with some phenothiazine derivatives. Trifluoperazine was observed to be the most potent inhibitor followed by promethazine and chlorpromazine. 6. Some anthelmintics viz. diethycarbamazine and centperazine were found to be highly potent inhibitors of the enzyme, significant inhibition of filarial Ca(2+)-ATPase was also observed with levamisole and suramine. 7. Studies indicate Ca(2+)-ATPase of S. cervi as a potential chemotherapeutic target. PMID- 1426526 TI - Efflux of polyamines from human lymphocytes and from L 1210 cells. AB - 1. In human lymphocytes alkalinization of the cytoplasm with monensin or NH4Cl promotes release of polyamines. The effect of NH4Cl is abolished by EGTA and diltiazem. 2. Concanavalin A also promotes an increase of the efflux, counteracted again by EGTA and diltiazem. 3. By effect of TPA, polyamine efflux is decreased in the first 90 min, and later increased. The activation is partially prevented by H7 and by sphingosine. 4. In contrast with human lymphocytes, L 1210 cells release actively endogenous polyamines, but slowly radioactive polyamines. 5. Concanavalin A does not activate the latter process; A 23187 and NH4Cl on the contrary promote a much higher increase in the efflux rate than in normal lymphocytes. EGTA and diltiazem partially counteract the effect of NH4Cl on the release of radioactivity. PMID- 1426527 TI - Purification and characterization of collagenolytic property of renal cathepsin L from arthritic rat. AB - 1. This paper describes the purification and characterization of collagenolytic property of renal cathepsin L isolated from kidney of rats rendered adjuvant arthritis. The enzyme was isolated by acid extraction, ammonium sulfate fractionation, Sephadex gel filtration, CM-Sephadex chromatography and Sephacryl S-300 chromatography. 2. The enzyme preparation was found to be homogeneous by gel filtration and SDS-polyacrylamide gel electrophoresis. The molecular weight of the enzyme was estimated to be 29,000. 3. Incubation of rat tail tendon collagen with purified cathepsin L resulted a conversion of cross-linked beta chain dimers into uncross-linked alpha-chain monomers. The pH optimum for collagen degradation by purified cathepsin L was found to be 3.5. This optimal pH is shifted to 4.5 when haemoglobin was used as a substrate for the enzyme. 4. Various activators and inhibitors were tested for their influence on the activity of cathepsin L. The purified enzyme showed a maximal activity in the presence of EDTA. Cysteine was also found to increase the activity of cathepsin L. This enzyme was strongly inhibited by iodoacetate, p-chloromercurobenzoate, mercuric chloride but not inhibited by pepstatin or PMSF. E-64 and leupeptin were also found to be strong inhibitors for cathepsin L. The degradation of rat tail tendon collagen by cathepsin L was completely inhibited by E-64. 5. The results presented in this investigation suggest that cathepsin L play a crucial role in the pathogenesis of adjuvant arthritis. PMID- 1426528 TI - Superinduction of ornithine decarboxylase by halogenated ribofuranosylbenzimidazoles. AB - 1. The effect of dichlororibofuranosylbenzimidazole (DiCl-RB), an inhibitor of hnRNA synthesis and casein kinase-2 activity, on ornithine decarboxylase (ODC) was investigated in a difluoromethylornithine (DFMO) resistant, ODC overproducing cell line. 2. In cells growing in the absence of DFMO, DiCl-RB provoked a marked, but transient increase in ODC activity and immunoreactive ODC content. 3. The ODC response to DiCl-RB was prevented by cycloheximide and was not due to stabilization of the enzyme. 4. The dibromo derivative analogue (DiBr-RB) exerted similar effects on ODC, but was effective at lower concentrations. 5. The halogenated ribofuranosylbenzimidazoles were ineffective in cells growing in the presence of DFMO and containing higher levels of ODC protein. PMID- 1426529 TI - Metabolism of [14C]arachidonic acid-labeled lipids in quiescent and OAG stimulated ascites tumor cells. AB - 1. A rapid uptake and esterification of [14C]arachidonic acid during the first 4 hr of cultivation of ascites cells in serum-deprived medium was observed followed by a fast turnover of the fatty acid. 2. Labeling and turnover of esterified arachidonate in individual phospholipid classes was in the order: phosphatidylcholine (PC) greater than phosphatidylinositol (PI) much greater than phosphatidylinositol-4-phosphate (PIP) and -4,5-bisphosphate (PIP2) greater than phosphatidylethanolamine (PE) greater than PE-plasmalogens. 3. In cells stimulated with 1-oleoyl-2-acetyl-sn-glycerol a transient course of arachidonic acid incorporation into PC, PI, PIP and PIP2 was determined peaking 30 min after stimulation, indicating both esterification and release under these conditions. 4. The release of arachidonate was blocked by quinacrine which is a specific inhibitor of phospholipase A2. PMID- 1426530 TI - Proteolytic processing sites producing the mature form of human cathepsin D. AB - 1. The proteolytic processing sites of human lysosomal aspartic protease cathepsin D at which the intermediate single-chain form was converted into the mature two-chain form were determined. 2. The two chains were isolated by reversed-phase HPLC in order to investigate the cleavage sites of the enzyme. 3. Protein sequencing of the heavy chain, which was presumed to be derived from the C-terminal side in the single-chain enzyme, gave an N-terminal Leu 105. In addition, it revealed that there were also minor sequences, which commenced with Gly 106 and Gly 107. 4. A small C-terminal peptide was isolated from the light chain, which had been digested with two kinds of exogenous proteases. Sequence determination of this peptide, which was characterized as a nonapeptide by mass spectrometry, suggested that the C-terminus of the light chain was Ser 98. 5. These results indicate that a Ser 98-Ala 99 bond and an Ala 104-Leu 105 bond are cleaved to release 6 amino acid residues between the two chains. PMID- 1426531 TI - Succinic semialdehyde dehydrogenase from mammalian brain: subunit analysis using polyclonal antiserum. AB - 1. NAD(+)-dependent succinic semialdehyde dehydrogenase was purified to apparent homogeneity from rat brain and highly purified from human brain. 2. Molecular exclusion chromatography of the purified enzymes on Sephadex G-150 and G-200 revealed M(r) values of 203,000 and 191,000 for rat and human, respectively. 3. Electrophoresis on sodium dodecylsulfate polyacrylamide gels revealed a single subunit of M(r) 54,000 for rat and 58,000 for human. Isoelectric focusing of the purified rat enzyme yielded a pI of 6.1. 4. For both proteins, Km values for short-chain aldehydes acetaldehyde and propionaldehyde ranged from 0.33 to 2.5 mM; Km values for succinic semialdehyde were in the 2-4 microM range. 5. The subunit structure of both enzymes was investigated in brain extracts and purified preparations by immunoblotting, using a polyclonal rabbit antiserum against the purified rat brain enzyme. 6. For rat and human extracts, single bands were detected at M(r) 54,000 and 58,000, comparable to findings in the purified preparations. Immunoblotting analyses in other species (guinea pig, hamster, mouse and rabbit) revealed single subunits of M(r) 54,000-56,500. PMID- 1426532 TI - Interaction of Zn2+ and Cu2+ ions with glyceraldehyde-3-phosphate dehydrogenase from bovine heart and rabbit muscle. AB - 1. Binding of Zn2+ and Cu2+ ions to GAPDHs from bovine heart and rabbit muscle resulted in a partial loss of enzymatic activity of both enzymes, in a time and metal ion concentration dependent manner. Cu2+ ions caused a much larger decrease of the activity than Zn2+ ions. 2. Addition of NAD+ or EDTA to either enzyme resulted in a protective effect on GAPDH activity. A similar protective effect was observed following addition of 2-mercaptoethanol to the enzyme solution. 3. The association constant for GAPDH-Zn2+ complex, calculated from equilibrium dialysis data, was 0.9 x 10(4) M-1 for the bovine heart GAPDH and 1.3 x 10(4) M-1 for the rabbit muscle enzyme. The association constant for GAPDH-Cu2+ complex was the same for both enzymes, 11.3 x 10(4) M-1. 4. Equilibrium dialysis data also revealed that in either enzyme the specific sites, binding the metal ions, are identical or very similar, and independent from each other. They are situated in the most conserved part of the enzyme molecule. 5. Some zinc was found in GAPDH preparations from bovine heart. It is discussed if Zn2+ ions could have a kind of modulation effect on GAPDH activity. PMID- 1426534 TI - Immunological identification of five members of the human facilitative glucose transporter family. PMID- 1426533 TI - Examination of the glycosidation state of five members of the human facilitative glucose transporter family. PMID- 1426535 TI - Inhibitors of quinone mediated electron transport. PMID- 1426536 TI - The effect of low pH preincubation on ATP synthesis and hydrolysis activities of isolated thylakoids. PMID- 1426537 TI - Sodium-dependent and -independent nucleobase transport in cultured LLC-PK1 epithelia. PMID- 1426538 TI - Ionic requirements of [3H]GBR-12935 binding to the dopamine transporter in canine striatal membranes. PMID- 1426539 TI - Nucleoside transporters in human placenta. PMID- 1426541 TI - The nature of betaine efflux from rat liver mitochondria. PMID- 1426540 TI - Reconstitution and kinetics of vacuolar H(+)-translocating ATPases from plants and animals. PMID- 1426542 TI - Choline transport into rat liver mitochondria. PMID- 1426543 TI - Mechanism of action of Ca(2+)-ATPase inhibitors. PMID- 1426544 TI - Inhibition of endothelial cell polyamine uptake by aliphatic diamines is dependent on chain length. PMID- 1426545 TI - Purification of the galactose/H+ symport protein of Escherichia coli. PMID- 1426546 TI - Activators and inhibitors of the motility of spermatozoa Fucus serratus [corrected]. PMID- 1426547 TI - Chemical modification of tissue inhibitor of metalloproteinase-1 (TIMP-1). PMID- 1426548 TI - The characterisation of peptidyl prolyl cis-trans isomerase (PPI) activity associated with the endoplasmic reticulum. PMID- 1426549 TI - Stability and unfolding studies on papain. PMID- 1426550 TI - The synthesis and expression of a gene coding for the HIV-1 protease. PMID- 1426551 TI - Mutagenesis of the glycerol dehydrogenase from Bacillus stearothermophilus. PMID- 1426552 TI - The kininogenase activity of human mast cell tryptase. PMID- 1426553 TI - GTP-binding proteins and protein phosphorylation substrates in central nervous system myelin. PMID- 1426554 TI - DNA sequence comparison between human and marsupial genes encoding PGP9.5--a neurone-specific ubiquitin C-terminal hydrolase. PMID- 1426555 TI - Identification of a neuronal specific DNA-binding protein within the rat preprotachykinin promoter. PMID- 1426556 TI - Neuronal expression of the tissue specific splicing protein SmN and its possible role in pre mRNA splicing. PMID- 1426557 TI - Studies on the mechanism of the inhibition of lipogenesis by growth hormone in sheep adipose tissue. PMID- 1426558 TI - The regulation of microsomal glucose-6-phosphatase differs between liver and kidney. PMID- 1426559 TI - Temperature dependent specific heat capacity (Cp) of G-actin and talin or talin vinculin bound to G-actin. PMID- 1426560 TI - Hydrolysis of xylo-oligosaccharides by a beta-xylosidase from the rumen anaerobic fungus Neocallimastix frontalis. PMID- 1426561 TI - Purification and characterization of a feruloyl/p-coumaroyl esterase from solid state cultures of the aerobic fungus Penicillium pinophilum. PMID- 1426562 TI - Alpha-tocopherol status in patients with rheumatoid arthritis: relationship to antioxidant activity. PMID- 1426563 TI - Influx of phosphate (Pi) and methylglucose in MG-63 osteoblasts. PMID- 1426564 TI - Benzopyrene metabolism and transport by cells in culture. PMID- 1426565 TI - Analysis of the receptor complement for insulin and insulin-like growth factor I (IGF-I) in the rat visceral yolk sac. PMID- 1426566 TI - The regulation of endopeptidase-24.11 expression on human osteoblast-like cells in culture. PMID- 1426567 TI - Inhibition of chymotrypsin by phenyl N-phenyl-phosphoramidochloridate. PMID- 1426568 TI - Bromoperoxidase of the macroalga Corallina officinalis. PMID- 1426569 TI - Synechococcus PCC6301 mutants possessing resistance to the tetrapyrrole biosynthesis inhibitor gabaculine. PMID- 1426570 TI - Proteins of photosystem 1 during chloroplast assembly and senescence in Festuca pratensis. PMID- 1426571 TI - A study of the 14 kDa phospholipase A2 from rat liver using a continuous fluorescent displacement assay for the enzyme. PMID- 1426572 TI - The use of tryptophan fluorescence to determine the stability of IgG binding proteins based upon the B domain of protein A from Staphylococcus aureus. PMID- 1426573 TI - Novel immunoglobulin binding proteins. PMID- 1426574 TI - The effect of an active site mutation of E. coli citrate synthase on NADH inhibition and KCl activation. PMID- 1426575 TI - FINDPROBE: a computer program to locate potential probe sequences in DNA. PMID- 1426576 TI - Lipoprotein lipase activity in tissues of the developing chick embryo. PMID- 1426577 TI - Identification and characterisation of glycosyl-inositolphospholipids in Toxoplasma gondii. PMID- 1426578 TI - Phospholipase A2 specificities determined in mixed substrate vesicles using a combination of continuous fluorescence displacement and quantitative HPLC analyses. PMID- 1426579 TI - Mechanisms of synthesis of polyunsaturated phosphatidylcholine molecular species by guinea pig liver. PMID- 1426580 TI - The U7 small nuclear RNA genes of Xenopus borealis. PMID- 1426582 TI - A preliminary analysis of the hybridization kinetics of an oligonucleotide to mRNA in tissue sections. PMID- 1426581 TI - Regulation of glutamate decarboxylase and enkephalin mRNA levels in rat striatum by chronic benzodiazepine treatment. PMID- 1426583 TI - Evidence for different isozymic forms of catalytic subunit of cyclic AMP dependent protein kinase in heart and lactating mammary gland of the rat. PMID- 1426584 TI - An examination of the transmembranous organisation of the sarcoplasmic reticulum (Ca(2+)-Mg2+)-ATPase using antipeptide antibodies. PMID- 1426586 TI - Probing the structure and function of the human erythrocyte glucose transporter. PMID- 1426585 TI - The N-terminal region of n-Chimaerin allows lipid modulation of the C-terminal p21rac-GTPase activating domain. PMID- 1426587 TI - Tissue-specific expression of facilitative glucose transporters: a rationale. PMID- 1426588 TI - The defective red cell anion transporter (band 3) in hereditary South East Asian ovalocytosis and the role of glycophorin A in the expression of band 3 anion transport activity in Xenopus oocytes. PMID- 1426589 TI - Structure-function of the ADP/ATP carrier. PMID- 1426590 TI - Studies of the structure and function of sarcoplasmic reticulum (Ca(2+)-Mg2+) ATPase using immunological approaches. PMID- 1426591 TI - Coupling of hydrolysis of ATP and the transport of Ca2+ by the calcium ATPase of sarcoplasmic reticulum. PMID- 1426593 TI - The Na(+)-translocating ATPase of Propionigenium modestum. PMID- 1426592 TI - Studies of the plasma membrane H(+)-ATPase of yeast and plants. PMID- 1426594 TI - Characterization of a sodiummotive NADH: ubiquinone oxidoreductase. PMID- 1426595 TI - Structural investigations of membrane proteins: the versatility of electron microscopy. PMID- 1426596 TI - beta-Lactamase fusion analysis of membrane protein assembly. PMID- 1426597 TI - Protein kinase C-delta and -epsilon: a functional appraisal. PMID- 1426599 TI - n-Chimaerin and neuronal signal transduction mechanisms. PMID- 1426598 TI - The role of specific isoforms of 14-3-3 protein in regulating protein kinase activity in the brain. PMID- 1426600 TI - Intermediate filament protein expression in differentiating Schwann cells. PMID- 1426601 TI - An evolutionary approach to myelin proteins and myelin-forming cells in the vertebrate brain. PMID- 1426602 TI - POU family transcription factors in sensory neurons. PMID- 1426603 TI - Comparisons of neuronal (PGP 9.5) and non-neuronal ubiquitin C-terminal hydrolases. PMID- 1426604 TI - Enolases and PGP9.5 as tissue-specific markers. PMID- 1426605 TI - Molecular pathology of Alzheimer's disease in sporadic and familial Alzheimer's disease with mutations in the amyloid precursor protein. PMID- 1426606 TI - The axonal membrane cytoskeletal protein A60 and the development of the spectrin/ankyrin-based neuronal membrane skeleton. PMID- 1426607 TI - Endocytosis in the brain: the role of clathrin light-chains. PMID- 1426608 TI - Structure of the genes encoding the neural cell adhesion molecules N-CAM and N cadherin. PMID- 1426609 TI - Insulin-activated protein kinases in fat and other cells. PMID- 1426610 TI - The mitogen-activated p70s6k. PMID- 1426611 TI - Early protein kinase and biosynthetic responses to insulin. PMID- 1426612 TI - Growth factor-activated kinases phosphorylate IRE-ABP. PMID- 1426613 TI - Metabolism of glycolipids: the role of glycolipid-binding proteins in the function and pathobiochemistry of lysosomes. PMID- 1426614 TI - Natural and synthetic inhibitors of glycosidases. PMID- 1426615 TI - Endogenous inhibition of glycosyltransferases of gangliosides: possible biochemical and morphogenetic functions. PMID- 1426616 TI - Activators and inhibitors of the plant plasma membrane 1,3-beta-glucan synthase. PMID- 1426617 TI - Cation activation and stabilization of Golgi beta 1,4-galactosyltransferase (lactose synthetase). PMID- 1426619 TI - What are and what are not imaginal discs: reevaluation of some basic concepts (Insecta, Holometabola). AB - Some general aspects of the concept of imaginal discs in the Holometabola are reevaluated. Their monolayer character and continuity with the surrounding epidermis are confirmed. Studies on the imaginal discs of the silkworm (Bombyx mori) and data from the literature show that the discs and their peripodial cells produce cuticle during larval life, as well as at metamorphosis. In B. mori it is demonstrated that adult and larval antennae are produced by the same cells or their progeny. The results also suggest that segments of the typically three segmented larval antenna of Holometabola are not scape, pedicel, and one segmented flagellum; at least segments 2 and 3 are of flagellar origin. Based on these and some additional facts it is argued that: (1) No larval organs are "replaced" at metamorphosis, but strict "sequential homology" is always maintained. (2) Imaginal discs are not undifferentiated structures destined to form the adult after larval breakdown, cannot be unambiguously defined, and do not represent qualitatively different epidermal structures. Classical imaginal discs (invaginated and present also in pre-final larval instars) arose several times independently and were not present in the larvae of ancestral Holometabola. (3) Since the disc cells are not undifferentiated and "embryonic" (if these words have a defined meaning at all), it is unreasonable to expect that the processes taking place in discs at metamorphosis would differ fundamentally from those occurring in other diploid metamorphosing epidermal cells. PMID- 1426618 TI - The gene for the helix-loop-helix protein, Id, is specifically expressed in neural precursors. AB - While mammalian neurogenesis has been characterized extensively, the molecules involved in regulating neural cell determination and differentiation remain ill defined. There is accruing evidence that various members of the basic helix-loop helix (bHLH) protein family critically regulate these biological processes in a number of tissues. Id, a negative regulator of bHLH proteins, was found to exhibit peak gene expression during mouse embryogenesis with a striking pattern in the central nervous system. Id transcripts were specifically localized to undifferentiated neural precursors of the ventricular zone and were not present in their differentiated derivatives. In addition, in the peripheral nervous system, dorsal root ganglia sensory precursors, known to be undifferentiated while dividing, also expressed Id mRNA. However, in the sympathetic nervous system and adrenal medulla, where differentiation and division occur simultaneously in precursors, Id was not expressed. Since Id transcript abundance inversely correlated with differentiation, this protein, similar to its Drosophila homolog, extramacrochaetae, may play a negative regulatory role in neural differentiation. PMID- 1426620 TI - Developmental sequence of expression of voltage-dependent currents in embryonic Xenopus laevis myocytes. AB - Although the development of several of the voltage-dependent currents in embryonic amphibian myocytes has been described, the overall muscle electrical development, particularly the relative times of expression of different voltage dependent currents, has not been addressed in a single study under one set of conditions. We have found that, in mesoderm isolated and cultured from neurula stage embryos, myocytes are identifiable before they express voltage-gated currents. These ionic currents are absent from all Xenopus mesodermal cells during the late gastrula/early neurula stages of embryonic development. At about the time of first somite segregation an inward rectifier K+ current is expressed in some myocytes, followed within 2 hr by a delayed rectifier K+ current. The density of both currents increases fourfold over the next 24 hr in culture. A Na+ current is not expressed in large numbers of myocytes until late in this culture period, at about the time that a slow Ca2+ current appears. Under our culture conditions the myocytes have a very low chloride conductance. A fast inactivating component to the outward K+ current is expressed in all myocytes by 24 hr in culture. In some experiments we dissociated embryos at later times and made recordings when all previously isolated myocytes expressed currents. In the late dissociations, most myocytes did not express currents, but developed them after a short period in culture. Because we have evidence that in vivo development is more closely approximated by the early dissociations, these results suggest that dissociation causes some degree of dedifferentiation. PMID- 1426621 TI - Developmentally regulated expression of three slow isoforms of myosin heavy chain: diversity among the first fibers to form in avian muscle. AB - At least three slow myosin heavy chain (MHC) isoforms were expressed in skeletal muscles of the developing chicken hindlimb, and differential expression of these slow MHC isoforms produced distinct fiber types from the outset of skeletal muscle myogenesis. Immunohistochemistry with isoform-specific monoclonal antibodies demonstrated differences in MHC content among the fibers of the dorsal and ventral premuscle masses and distinctions among fibers before splitting of the premuscle masses into individual muscles (Hamburger and Hamilton Stage 25). Immunoblot analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of myosin extracted from the hindlimb demonstrated the presence throughout development of different mobility classes of MHCs with epitopes associated with slow MHC isoforms. Immunopeptide mapping showed that one of the MHCs expressed in the embryonic limb was the same slow MHC isoform, slow MHC1 (SMHC1), that is expressed in adult slow muscles. SMHC1 was expressed in the dorsal and ventral premuscle masses, embryonic, fetal, and some neonatal and adult hindlimb muscles. In the embryo and fetus SMHC1 was expressed in future fast, as well as future slow muscles, whereas in the adult only the slow muscles retained expression of SMHC1. Those embryonic muscles destined in the adult to contain slow fibers or mixed fast/slow fibers not only expressed SMHC1, but also an additional slow MHC not previously described, designated as slow MHC3 (SMHC3). Slow MHC3 was shown by immunopeptide mapping to contain a slow MHC epitope (reactive with mAb S58) and to be structurally similar to a MHC expressed in the atria of the adult chicken heart. SMHC3 was designated as a slow MHC isoform because (i) it was expressed only in those muscles destined to be of the slow type in the adult, (ii) it was expressed only in primary fibers of muscles that subsequently are of the slow type, and (iii) it had an epitope demonstrated to be present on other slow, but not fast, isoforms of avian MHC. This study demonstrates that a difference in phenotype between fibers is established very early in the chicken embryo and is based on the fiber type-specific expression of three slow MHC isoforms. PMID- 1426622 TI - Position-specific expression of the annulin protein during grasshopper embryogenesis. AB - Annulin, named for its annular expression in developing limb buds, is a approximately 100 kDa membrane-associated protein that is expressed in a complex and changing pattern during grasshopper embryogenesis. Its expression is dynamic along the developing midline and in the mesoderm, transient in neuroepithelial sheath cells around mitotic neuroblasts, and position-specific in circumferential stripes in each limb bud segment. Annulin expression begins along the midline of the embryo at the onset of gastrulation. Mesoderm cells express the protein as they migrate away from the midline as do new cells that come to lie at the midline. During neurogenesis, annulin expression disappears from many midline cells until only a specific subset of midline glial cells expresses high levels of the protein. Starting at the beginning of neurogenesis, sheath cells express annulin in correlation with the mitotic activity of the neuroblasts they surround. PMID- 1426624 TI - FGF-mediated aspects of skeletal muscle growth and differentiation are controlled by a high affinity receptor, FGFR1. AB - Fibroblast growth factors (FGFs) and FGF receptors (FGFRs) play major roles in vertebrate embryogenesis, including control of skeletal muscle growth and differentiation. Understanding their roles requires delineating the specific FGF and FGFR isoforms involved. This study analyzes the FGFR transcripts found in a model mouse skeletal myoblast cell line (MM14) during growth and terminal differentiation. MM14 cells express transcripts for FGFR1 (flg) but not FGFR2 (bek). The predominate FGFR1 transcript contains three immunoglobulin (Ig)-like domains in the extracellular ligand binding region. Approximately one-fourth of the three Ig-like domain transcripts possess a 6-nt deletion between the first and second Ig-like domains which after translation would result in deletion of an Arg-Arg pair. Cloning of mouse genomic DNA surrounding the region of the FGFR1 6 nt deletion indicates that the deletion is derived by alternative splicing of FGFR1 transcripts. Transcripts containing two Ig-like domains account for less than 5% of total FGFR1 mRNA in MM14 cells. A survey of RNA from mouse tissues indicated that two Ig-like domain FGFR1 transcripts are rare in all tissues except in lung, in which the two Ig-like domain form accounts for roughly 70% of the lung FGFR1 mRNA. PCR RACE cloning studies disclosed 162 nt of additional FGFR1 5'-flanking RNA which was highly GC-rich. FGFR1 transcripts decline 8- to 10-fold during low serum, (-)FGF-mediated differentiation of MM14 cultures. The kinetics of the FGFR1 mRNA decline is similar to the previously described differentiation-dependent decrease in cell surface FGF receptors. PMID- 1426623 TI - Differential transcription of Pgk genes during spermatogenesis in the mouse. AB - We have analyzed the occurrence of transcripts produced from the ubiquitously expressed, X-linked Pgk-1 gene and the testis-specific, autosomal Pgk-2 gene during spermatogenesis in the mouse. We found that tissue specificity, developmental specificity, and cell-type specificity of these mRNAs parallel that previously reported for the two protein isozymes of phosphoglycerate kinase (PGK) encoded by these two genes. This indicates that primary regulation of differential expression of the Pgk genes during spermatogenesis is exerted at the transcriptional level. We first detected Pgk-2 mRNA in preleptotene spermatocytes, indicating that transcription of Pgk-2 is initiated coincident with the onset of meiosis in male germ cells, and then continues to increase in later spermatocytes and postmeiotic round spermatids. This expression initiates prior to an initial decline in Pgk-1 transcript levels observed in pachytene spermatocytes, which apparently follows inactivation of the single X chromosome in spermatogenic cells. However, unlike cessation of Pgk-1 transcription from the inactivated X chromosome in female somatic cells, we show that inactivation of the Pgk-1 locus in spermatogenic cells is not followed by methylation of a key CpG dinucleotide in the promoter region. These results support the idea that specific expression of the Pgk-2 gene in meiotic and postmeiotic spermatogenic cells has evolved to compensate for reduced levels of Pgk-1 gene product caused by transient X-chromosome inactivation in these cells. They further suggest that reinitiation of transcription of the paternal Pgk-1 allele shortly after fertilization is facilitated by constitutive hypomethylation in the promoter region of this gene throughout spermatogenesis. PMID- 1426625 TI - Mutant yolk proteins lead to female sterility in Drosophila. AB - Specific mutations in the yolk protein genes, yp1 and yp2, of Drosophila melanogaster cause the yolk proteins (YPs) they encode to precipitate, ultimately resulting in female sterility. YPs of the yp1 mutant fs(1)1163 are secreted normally but then precipitate as globules and occasionally as crystalline fibers in the subbasement membrane space of the fat body (Butterworth et al., 1991, J. Cell Biol. 112, 727-737). The present ultrastructural and immunological studies of the fat body of the yp2 mutant fs(1)K313 show that YP also precipitates as globules in the same tissue compartment. The globules are also incapable of passing into the hemolymph but they are morphologically distinct from those of fs(1)1163. Similar analyses were performed on developing oocytes in wild type and both mutant strains. YP-containing aggregates, ultrastructurally similar to those in the fat body of each respective mutant, were found in the space between the plasmalemma and the vitelline membrane and embedded within the membrane itself. The evidence suggests that the precipitates interfere with the correct assembly of the eggshell membranes, leading to the sterile phenotype. Immunogold studies demonstrate that newly synthesized YPs in the normal and mutant strains share secretory vesicles with putative, vitelline membrane proteins and that the translocation of follicle cell YP is not through the membrane along the interfollicular spaces but directly through the plasmalemma facing the oocyte. Further the YP precipitates in the mutants permit visualization of the polarity of exocytosis of YP from the follicle cells. PMID- 1426626 TI - Heterogeneity of Tau proteins during mouse brain development and differentiation of cultured neurons. AB - Tau microtubule-associated proteins constitute a group of developmentally regulated neuronal proteins. Using the high-resolution two-dimensional polyacrylamide gel electrophoresis system, we have resolved more than 60 distinct Tau isoforms in the adult mouse brain. Tau protein heterogeneity increases drastically during the second week of brain development. In neuronal primary cell cultures, some of these developmental changes can be observed. The increase of Tau heterogeneity in culture is more limited and reaches a plateau after a period corresponding to the second week of development. Most, if not all, of the vast Tau heterogeneity can be attributed to intensive post-translational phosphorylation, which may affect the structure of the proteins. PMID- 1426627 TI - Behavior of structurally divergent alpha-tubulin isotypes during Drosophila embryogenesis: evidence for post-translational regulation of isotype abundance. AB - Two major alpha-tubulin isotypes are present during Drosophila embryogenesis: an evolutionarily divergent maternal isotype that is synthesized only in the ovary and deposited in the oocyte and a highly conserved constitutive isotype that is both maternally supplied and zygotically synthesized. A maternal isotype-specific antibody and a monoclonal antibody that recognizes both the maternal and constitutive isotypes were characterized and used to determine the distribution and abundance of alpha-tubulins during embryogenesis. Both isotypes are abundant and assemble into all classes of microtubules from the syncytial blastoderm stage until completion of germ band retraction. During subsequent development, however, the maternal isotype is retained only in the developing CNS, and later in a subset of connective fibers within the CNS. In contrast, total alpha-tubulin levels remain high in essentially all tissues throughout embryogenesis, indicating that most tissues selectively accumulate the constitutive isotype. To determine if selective accumulation of the constitutive isotype requires zygotic synthesis of this protein, mutant embryos that do not contain functional constitutive alpha-tubulin genes were examined. In these embryos, as in wild type, the maternal isotype decreases to background levels in tissues that retain high levels of the constitutive isotype. The constitutive isotype therefore appears to be more stable than the maternal isotype in most tissues. Differences in isotype stability may play an important role in determining the developmental pattern of isotype accumulation in Drosophila embryos. PMID- 1426628 TI - Perturbations in morphogen gradients induce budding in hydra. AB - Lateral grafting of small pieces of midregion tissue into different levels of the hydra body column was done to assess the influence of the host hypostome and basal disc (or, of the underlying morphogenetic gradients) in inducing secondary structures in the transplanted tissue; and also to identify the role, if any, of the induced secondary structures (or, perturbed morphogen gradients) on the pattern of the host. The same midpiece tissue differentiated to a basal disc when grafted near the host hypostome, and to a small hypostome with tentacles when grafted near the host basal disc. Chimeras with induced secondary basal discs showed a phenomenal increase in budding compared to the controls and to the chimeras having induced hypostomes. These results indicate a positive cross reaction between both organizing regions during patterning in hydra. PMID- 1426629 TI - The rapid transient decrease of sn-1,2-diacylglycerol in progesterone-stimulated Xenopus laevis oocytes is the result of an ethanol artifact. AB - Full-grown Xenopus laevis oocytes resume meiosis (meiotic maturation) in response to progesterone stimulation. Three studies have shown that sn-1,2-diacylglycerol (DAG), the intracellular activator of protein kinase C, may be involved in this process (Wasserman et al., J. Exp. Zool. 255, 63-71, 1990; Varnold and Smith, Development 109, 597-604, 1990; Stith et al., J. Cell Physiol. 149, 252-259, 1991). Two of these studies (Varnold and Smith, 1990; Stith et al., 1991) found a rapid, but transient decrease in the levels of DAG of approximately 25 to 30% within 5 to 30 sec following the addition of progesterone to the oocytes. We have investigated this rapid decline in oocyte DAG. We also found a 20 to 34% decrease in DAG/oocyte within the first 5 to 40 sec following the addition of steroid to the culture medium. However, a similar rapid and transient decrease in oocyte DAG levels was also observed in response to ethanol. Ethanol is used as the vehicle to deliver progesterone to the oocyte culture medium. Therefore, the rapid transient decline in DAG appears to be an artifact of ethanol perturbing the production and/or turnover of DAG within the oocyte and not a physiological response of the oocyte to progesterone. PMID- 1426630 TI - Ameiotic, a gene that controls meiotic chromosome and cytoskeletal behavior in maize. AB - Microtubule organization during the novel cell division of ameiotic microsporocytes was examined using indirect immunofluorescence microscopy. A recessive mutation of the maize gene Ameiotic causes the replacement of meiosis I with a synchronized mitotic division (Palmer, R. G. (1971). Chromosoma 35, 233 246). All identifiable cytological features of this division, including chromosome behavior and microtubule organization, were typical of somatic cell division. Significantly, a cortical microtubule band was observed during prophase in ameiotic cells. In most somatic plant cells, a preprophase band of microtubules (PPB) predicts the cortical site where the future cell plate will join the sidewall. Similar structures, however, are absent in all meiotic and postmeiotic reproductive cells examined to date. These disruptions are consistent with a model where the wild-type Ameiotic gene encodes a product which acts during or before G2 and is necessary for initiating several independent meiotic processes, including both meiotic chromosome behavior and microtubule organization. The ameiotic mutation provides additional evidence that aspects of cytoskeletal organization unique to meiosis are genetically controlled. Finally, the presence of a PPB during the ameiotic division supports a model whereby multiple mechanisms are used to determine and maintain division plane polarity during normal meiosis. PMID- 1426631 TI - The east gene of Drosophila melanogaster is expressed in the developing embryonic nervous system and is required for normal olfactory and gustatory responses of the adult. AB - Drosophila melanogaster larvae and adults respond to a wide range of chemosensory stimuli. We describe the genetics and developmental expression of the east gene, mutations which result in adult-specific chemosensory defects. The original isolate of east is semidominant for the behavioral phenotype. Several mutations have been generated, some of which are recessive lethals and others that are viable alleles that show a recessive, adult-specific, chemosensory defect. No larval chemosensory defects were observed. The east gene is expressed in the neurogenic region at the time of neuroblast segregation and in cells in the peripheral and central nervous system. Our results suggest that east+ expression in the nervous system is required for a normal adult chemosensory response and both increases and decreases in levels of the gene product result in a mutant phenotype. PMID- 1426632 TI - Sequence and localization of human NASP: conservation of a Xenopus histone binding protein. AB - In this study the sequence and localization of human testicular NASP (nuclear autoantigenic sperm protein) are reported. NASP cDNA contains 2561 nt encoding a protein of 787 amino acids. The open reading frame contains 2446 nt followed by an ochre stop codon (TAA) and 104 nucleotides of untranslated sequence containing a poly(A) addition signal 10 bases upstream of the poly(A) tail. Northern blot analysis of human testis poly(A) mRNA indicates a message of approximately 3.2 kb. Multiple sequence alignment (MSA) analysis of the encoded human NASP amino acid sequence with the sequence for the Xenopus histone-binding protein N1/N2 and the rabbit NASP amino acid sequence demonstrates that the human sequence and the Xenopus sequence have extensive amino acid homology upstream of the rabbit initiation codon. Significantly, there is an 85% identity between the human and the rabbit NASP sequences when the alignment starts at the N-terminal of the rabbit sequence and at amino acid 101 of the human sequence. The nuclear translocation signal found in N1/N2 and rabbit NASP is completely conserved in human NASP. The first histone-binding domain of Xenopus is 70% identical and 90% similar to the human NASP domain. The second histone-binding domain of Xenopus is 48% identical and 71% similar to the human NASP domain. MSA analysis of the three sequences generated an unrooted ancestral tree with two branches, indicating that fewer amino acid changes have occurred between the Xenopus and the human sequences than between the Xenopus and the rabbit sequences. In the human testis, NASP is localized predominantly in primary spermatocytes and round spermatids. Spermatogonia, Sertoli cells, Leydig cells, peritubular cells, and other somatic cells do not stain. Human spermatozoa contain NASP in the acrosomal region. Following the acrosome reaction, some NASP remains in the equatorial and postacrosomal regions. We propose that mammalian testes and sperm contain a histone-binding protein which may play a role in regulating the early events of spermatogenesis. PMID- 1426634 TI - A deficiency in the mechanism for p34cdc2 protein kinase activation in mouse embryos arrested at 2-cell stage. AB - Mouse embryos of the ddY strain fertilized in vitro undergo the first cleavage to the 2-cell stage but not the second cleavage even 45 hr after insemination (2 cell block). We examined the phosphorylation state of p34cdc2 and histone H1 kinase activity in mouse 2-cell embryos to investigate the relationship of p34cdc2 with 2-cell block. In the first mitotic cell cycle, the amount of phosphorylated forms of p34cdc2, which were detected as the bands of retarded mobility on SDS-PAGE followed by immunoblotting with anti-p34cdc2 antibody, increased during interphase and abruptly decreased at M phase. Concomitant with this dephosphorylation, histone H1 kinase activity was increased. After the embryos cleaved to the 2-cell stage, the amounts of phosphorylated forms of p34cdc2 increased up to 33 hr after insemination. However, the activation of histone H1 kinase did not occur and the states of phosphorylation of p34cdc2 did not show any significant changes until 45 hr. In contrast, 2-cell embryos of B6C3F1 mice, which do not show a 2-cell block and develop normally to blastocysts in vitro, exhibit the dephosphorylation of p34cdc2 and an increase in histone H1 kinase activity between 31 and 45 hr after insemination. When the ddY mouse embryos arrested at the 2-cell stage were treated with okadaic acid, an inhibitor of protein phosphatases 1 and 2A, the dephosphorylation of p34cdc2 occurred and histone H1 kinase activity increased. The chromosomes of these embryos stained with 4',6'-diamidino-2-phenylindole revealed the initiation of condensation. These results suggest that 2-cell-blocked embryos contain enough p34cdc2 to induce mitotic events but the protein remains in a latent form. PMID- 1426633 TI - Transcriptional regulation of the murine k-FGF gene in embryonic cell lines. AB - Previous studies have shown that embryonal carcinoma (EC) cells express the fibroblast growth factor k-FGF; however, there is a large decrease in the expression of this gene when EC cells differentiate. In addition, it has been shown that differentiation of mouse F9 EC cells reduces the expression of a reporter gene under the control of both the putative human k-FGF promoter and an enhancer-like element that is located in the third exon of the k-FGF gene. Given the low degree of sequence similarity between the human k-FGF gene and the murine k-FGF gene upstream of the transcription start site, it was unclear whether human sequences mimic fully the regulation of the k-FGF gene in mouse cells. To address this question, we have examined the expression of gene constructs containing various regions of the murine k-FGF gene in two mouse EC cell lines and one mouse embryonic stem (ES) cell line. Our results demonstrate that the mouse 5' flanking region, like the human 5' flanking region, cannot support expression of the reporter gene. In both EC cell lines and the ES cell line, expression of the reporter gene is elevated 10- to 100-fold by the addition of a 316-bp region taken from the third exon of the murine k-FGF gene. In addition, we provide evidence that octamer binding proteins are involved in the regulation of the k FGF gene. Last, this study has identified regions upstream of the transcription start site that appear to regulate the expression of the murine k-FGF gene in EC cells and in ES cells. PMID- 1426635 TI - The zfh-2 gene product is a potential regulator of neuron-specific dopa decarboxylase gene expression in Drosophila. AB - We have studied a 40-bp upstream regulatory region of the DOPA decarboxylase gene (Ddc) which is important for cell-specific expression in the Drosophila central nervous system (CNS). This region contains two redundant elements which when simultaneously mutated result in lowered DDC expression in serotonin neurons. We uncovered a protein binding site within one of these elements and have cloned a factor which binds to the site. This factor is the product of the zfh-2 gene, a complex homeodomain/zinc finger protein previously identified by binding to an opsin regulatory element. The in vivo profile of ZFH-2 in the larval CNS shows intriguing overlap with DDC in specific serotonin and dopamine neurons. We show that ZFH-2 is related to a human transcription factor ATBF1. The multiple homeodomain and zinc finger motifs in these two proteins show a similar linear arrangement which implies coordinate action among the motifs. In addition, the homology defines a new homeodomain subtype. PMID- 1426636 TI - Glycolipid linkage of a polyspermy blocking glycosidase to the ascidian egg surface. AB - Ascidian eggs release N-acetylglucosaminidase rapidly into the seawater following fertilization. This glycosidase is detected seconds after fertilization, and histochemical tests suggest the cell surface as the prefertilization storage site (Lambert, C. C. (1989). Development 105, 415-420). Living eggs of Ascidia ceratodes, A. callosa, and A. paratropa all cleave a fluorogenic substrate in seawater. Following cell surface biotinylation and activation of the eggs, enzyme activity binds to streptavidin further substantiating the cell surface localization. The released glycosidase has a molecular weight of 180 kDa by size exclusion chromatography and exhibits bands at 62 and 70 kDa by SDS-PAGE, suggesting a possibly multimeric enzyme. The enzyme is released by a glycophosphatidylinositol-specific phospholipase C and HNO2 deamination, both of which are specific indicators of linkage to the cell surface via phosphatidylinositol. The enzyme from unfertilized eggs is quite hydrophobic in Triton X-114 phase partition experiments but becomes hydrophyllic after release by activation or deamination. All of these observations are consistent with the glycosidase being anchored to the cell surface via a GPI anchor that is cleaved at fertilization to yield the soluble form of the enzyme which helps protect the egg against polyspermy. We discuss the possible role of a cell surface PLC in this release. PMID- 1426637 TI - Genetic approaches to understanding muscle development. AB - The analysis of both naturally occurring and experimentally induced mutants has greatly advanced our understanding of muscle development. Molecular biological techniques have led to the isolation of genes associated with inherited human diseases that affect muscle tissues. Analysis of the encoded proteins in conjunction with the mutant phenotypes can provide powerful insights into the function of the protein in normal muscle development. Systematic searches for muscle mutations have been made in experimental systems, most notably the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans. In addition, known muscle protein genes from other organisms have been used to isolate homologs from genetically manipulatable organisms, allowing mutant analysis and the study of protein function in vivo. Mutations in transcription factor genes that affect mesoderm development have been isolated and genetic lesions affecting myofibril assembly have been identified. Genetic experiments inducing mutations and rescuing them by transgenic methods have uncovered functions of myofibrillar protein isoforms. Some isoforms perform muscle-specific functions, whereas others appear to be replaceable by alternative isoforms. Mutant analysis has also uncovered a relationship between proteins at the cell membrane and the assembly and alignment of the myofibrillar apparatus. We discuss examples of each of these genetic approaches as well as the developmental and evolutionary implications of the results. PMID- 1426638 TI - Structural analysis of muscle development: transverse tubules, sarcoplasmic reticulum, and the triad. AB - Increased interest in the mechanism of excitation-contraction (E-C) coupling over the last few years has been accompanied by numerous investigations into the development of the underlying cellular structures. Areas of particular interest include: (1) the compartmentalization and specialization of an external and an internal membrane system, the T-tubules, and the sarcoplasmic reticulum, respectively; (2) interactions between the membrane proteins of both systems upon the formation of a junction, the triad; and (3) membrane-cytoskeletal interactions leading to the orderly arrangement of the triads with respect to the myofibrils. Structural studies using newly available specific molecular probes and a variety of in vivo and in vitro model systems have provided new insights into the cellular and molecular mechanisms involved in the development of the E-C coupling apparatus in skeletal muscle. PMID- 1426639 TI - Myogenic cell lineages. AB - For many years the mechanisms by which skeletal muscles in higher vertebrates come to be composed of diverse fiber types distributed in distinctive patterns has interested cell and developmental biologists. The fiber composition of skeletal muscles varies from class to class and from muscle to muscle within the vertebrates. The developmental basis for these events is the subject of this review. Because an individual multinucleate vertebrate skeletal muscle fiber is formed by the fusion of many individual myoblasts, more attention, in recent times, has been directed toward the origins and differences among myoblasts, and more emphasis has been placed on the lineal relationship of myoblasts to fibers. This is a review of studies related to the concepts of myogenic cell lineage in higher vertebrate development with emphases on some of the most challenging problems of myogenesis including the embryonic origins of myogenic precursor cells, the mechanisms of fiber type diversity and patterning, the distinctions among myoblasts during myogenesis, and the current hypotheses of how a variety of factors, intrinsic and extrinsic to the myoblast, determine the definitive phenotype of a muscle fiber. PMID- 1426640 TI - Epithelial-mesenchymal interactions in the outgrowth of limb buds and facial primordia in chick embryos. AB - The facial primordia in the chick embryo begin as rounded swellings that surround the primitive mouth and these grow out to form the beak. The control of proximodistal outgrowth is not well understood but may involve similar mechanisms to the limb bud. In order to test this hypothesis, combinations were made between epithelium and mesenchyme from facial primordia and limb buds. Signals from all three types of facial mesenchyme (frontonasal mass, mandibular, and maxillary) maintained the thickened apical ectodermal ridge of limb epithelium for up to 48 h. Combinations of tissues from the frontonasal mass mesenchyme and limb epithelium underwent substantial and correct morphogenesis. In contrast, poor development was observed in combinations with mandibular mesenchyme. Signals from frontonasal mass epithelium promoted outgrowth and morphogenesis of limb mesenchyme whereas mandibular and maxillary epithelium did not support joint morphogenesis. The results suggest that signals employed in the epithelial mesenchymal interactions in facial primordia are similar but not identical to those signals used in the limb bud. PMID- 1426641 TI - Effects of the steroid hormone, 20-hydroxyecdysone, on the growth of neurites by identified insect motoneurons in vitro. AB - During metamorphosis in the hawkmoth, Manduca sexta, identified larval leg motoneurons survive the degeneration of their larval targets to innervate new muscles of the adult legs. The dendrites and axon terminals of these motoneurons regress at the end of the larval stage and then regrow during adult development. Previous studies have implicated the insect steroid, 20-hydroxyecdysone (20-HE), in similar examples of dendritic reorganization during metamorphosis. The present studies were undertaken to test whether 20-HE acts directly on the leg motoneurons to regulate dendritic growth. Larval leg motoneurons were labeled with a fluorescent dye to permit their identification in culture following the dissociation of thoracic ganglia at later stages of development. Leg motoneurons isolated from early pupal stage animals (just before the normal onset of dendritic regrowth) survived in vitro and grew processes regardless of whether 20 HE was added to the culture medium. The extent of process outgrowth, however, as measured by the total length of all processes and the number of branches, was significantly greater for motoneurons maintained in the presence of 20-HE. The enhancement could be blocked by the addition of a juvenile hormone analog. By contrast, larval leg motoneurons that were isolated just before the normal period of dendritic regression did not show enhanced growth of neurites in the presence of 20-HE. The results suggest that 20-HE acts directly on the leg motoneurons to regulate the growth of processes during metamorphosis. PMID- 1426642 TI - Interaction of Wnt and activin in dorsal mesoderm induction in Xenopus. AB - Both the activin and Wnt families of peptide growth factors are capable of inducing dorsal mesoderm in Xenopus embryos. Presumptive ventral ectoderm cells isolated from embryos injected with Xwnt8 mRNA were cultured in the presence of activin A to study the possible interactions between these two classes of signaling proteins. We find that overexpression of Xwnt8 RNA alters the response of ventral ectoderm to activin such that ventral explants differentiate dorsoanterior structures including notochord and eyes. This response is similar to the response of dorsal ectoderm to activin alone. When embryos are irradiated with uv light to inhibit dorsal axis formation, ectodermal explants differentiate notochord when they are induced by a combination of both signaling factors, but not when cells receive only one inducing signal (activin or Xwnt8). This result is further supported by the observation that goosecoid (gsc) mRNA, an early marker for dorsal mesoderm, is expressed in these explants only when they are injected with Xwnt8 mRNA followed by exposure to activin. Early morphogenetic movements of the induced cells and activation of muscle-specific actin and Brachyury (Xbra) genes also reveal a cooperation of activin A and Xwnt8 in mesoderm induction. PMID- 1426644 TI - Expression analysis of a Notch homologue in the mouse embryo. AB - The Drosophila Notch gene has been shown to be involved in the determination of fate in a number of different cell types. Similarly, Notch homologues in Caenorhabditis elegans are involved in cell decision-making steps. It is of interest to determine if a mammalian Notch homologue plays a role in cell fate determination. We have isolated cDNA from a mouse Notch gene using low-stringency hybridization with probes derived from the Xenopus Notch gene. Sequence analysis reveals that this gene possesses EGF repeats, Notch/lin-12 repeats, and CDC 10/SWI-6 repeats, characteristic of other Notch homologues. Northern analysis revealed that the transcript size was roughly 10 kb as has been found for the other Notch genes. We have studied the expression pattern of the gene by both conventional and whole mount in situ hybridization. Expression patterns were consistent with mouse Notch having a determinative role in the formation of mesoderm, somites, and the nervous system. PMID- 1426643 TI - Sexually dimorphic expression of a laryngeal-specific, androgen-regulated myosin heavy chain gene during Xenopus laevis development. AB - Masculinization of the larynx in Xenopus laevis frogs is essential for the performance of male courtship song. During postmetamorphic (PM) development, the initially female-like phenotype of laryngeal muscle (slow and fast twitch fibers) is converted to the masculine form (entirely fast twitch) under the influence of androgenic steroids. To explore the molecular basis of androgen-directed masculinization, we have isolated cDNA clones encoding portions of a new Xenopus myosin heavy chain (MHC) gene. We have detected expression of this gene only in laryngeal muscle and specifically in males. All adult male laryngeal muscle fibers express the laryngeal myosin (LM). Adult female laryngeal muscle expresses LM only in some fibers. Expression of LM during PM development was examined using Northern blots and in situ hybridization. Males express higher levels of LM than females throughout PM development and attain adult levels by PM3. In females, LM expression peaks transiently at PM2. Treatment of juvenile female frogs with the androgen dihydrotestosterone masculinizes LM expression. Thus, LM appears to be a male-specific, testosterone-regulated MHC isoform in Xenopus laevis. The LM gene will permit analysis of androgen-directed sexual differentiation in this highly sexually dimorphic tissue. PMID- 1426645 TI - Colocalization of transforming growth factor-alpha and a functional epidermal growth factor receptor (EGFR) to the inner cell mass and preferential localization of the EGFR on the basolateral surface of the trophectoderm in the mouse blastocyst. AB - Results of previous studies suggested that responses of mouse blastocysts to TGF alpha/EGF treatment are mediated by EGF receptors (EGFR) located on the apical surface of the trophectoderm (TE). We report here results of experiments using gold-labeled EGF that confirm the presence of these apically located EGFRs. In addition, immunoelectron microscopy (IEM) studies using anti-EGFR antibodies indicate that the receptor is preferentially distributed on the basolateral surface of the TE. Furthermore, the receptor is also present on the inner cell mass (ICM) and is likely to be functional, since treatment of isolated ICMs with TGF-alpha affects [35S]methionine uptake and incorporation into acid-insoluble material. IEM was also used to demonstrate that EGF, which is not synthesized by the mouse preimplantation embryo, is present in both the oviduct and the uterus. Maternally derived EGF is present in both ICM and TE cells in freshly isolated blastocysts, but is present in greatly reduced amounts following overnight culture of blastocysts in vitro. Last, IEM was also used to demonstrate that TGF alpha is preferentially localized to the ICM and polar TE. The co-localization of TGF-alpha and functional EGFRs to the ICM and polar TE suggests potential autocrine, juxtacrine, and paracrine roles for TGF-alpha in blastocyst development. PMID- 1426646 TI - Mechanisms of synaptic fatigue in a developing autonomic ganglion. AB - Synaptic transmission in developing systems has often been noted to exhibit depression or failure at moderate frequencies of stimulation. While this is often presumed to be a transient, nonspecific inability of developing systems to meet the demands of synaptic transmission, this report demonstrates that such failure in the choroidal neurons of the embryonic ciliary ganglion is due to muscarinically mediated inhibition. Although the ganglion is composed of both choroid and ciliary neurons, only the choroid neurons exhibit the muscarinic depression, and only during embryonic development. The pharmacological properties of the relevant receptor are different from those of the muscarinic receptor involved in presynaptic inhibition in adult autonomic systems. Receptor-mediated, synaptic failure during development may serve to protect immature postsynaptic neurons from potentially toxic overstimulation. PMID- 1426647 TI - Programmed nuclear death: apoptotic-like degradation of specific nuclei in conjugating Tetrahymena. AB - During conjugation in the ciliated protozoan Tetrahymena, new macronuclei differentiate from germinal zygotic micronuclei while parental (old) macronuclei are eliminated in two stages, condensation or pycnosis coincident with cessation of transcription followed by resorption. We show that pycnosis is accompanied by degradation of old macronuclear DNA into oligonucleosome-sized fragments, a hallmark of programmed cell death, or apoptosis, in a variety of eukaryotic systems. As expected, oligonucleosome formation does not occur in the new micro- and macronuclei, confirming the coordination of different developmental fates for different nuclei in a common cytoplasm. NULLI 3 conjugants have wild-type old macronuclei but lack chromosome 3 germinally and hence in the new macronucleus. In NULLI 3 conjugants, old macronuclear pycnosis and oligonucleosome fragmentation occur normally but the resorption step fails, and the pycnotic old macronucleus is retained, demonstrating that the two steps are genetically separable and thus distinct and implying that genes on chromosome 3 in the new macronucleus are required for the resorption step. Comparison of whole cell polypeptides synthesized during stages of macronuclear development in both wild type and NULLI 3 crosses reveal similar profiles. However, a polypeptide (apparent M(r) of 53 kDa) synthesized during old macronuclear elimination is not observed in NULLI 3 conjugants; its role, if any, in elimination of the old macronucleus is unknown. The results show that the old macronucleus is selectively destroyed by a mechanism which is remarkably similar to apoptosis in other eukaryotes and that the zygotic genome is required for the resorption step. PMID- 1426648 TI - Localization of a chymotrypsin-like protease to the perivitelline space of Xenopus laevis eggs. AB - A chymotrypsin-like protease is released from Xenopus laevis eggs at activation and is involved in conversion of the vitelline envelope to the fertilization envelope. To localize this enzyme in unactivated and activated eggs, we used the synthetic peptide substrate succinylalanylalanylprolylphenylalanyl-4-methoxy-2 naphthylamide whose product can be visualized using transmission electron microscopy. Protease product was localized within the perivitelline space of unactivated eggs, appearing as strings of beads. No protease activity was detected in activated eggs, which is consistent with the observation that the protease is released from the egg at activation. PMID- 1426649 TI - Current status and problems in preclinical assessment of immunomodulators. PMID- 1426650 TI - Popliteal lymph node assay as a tool to predict drug-induced GvH-like reactions. AB - The popliteal lymph node (PLN) assay was proposed to study a panel of drug induced clinical manifestations, e.g. lupus syndrome, serum sickness-like disease, lymphadenopathy, scleroderma-like reaction, the mechanism of which was suggested as being similar to a graft-versus-host (GvH) reaction, hence the term GvH-like reaction. This assay can readily be performed in either the mouse or rat. The commonest endpoint is PLN weight, but cellularity and lymphocyte phenotype analysis can also be determined. Experiments so far show that most drugs and chemicals known to induce such complications in man can be detected by the PLN assay and false-positive responses are extremely few. Interestingly, preliminary results indicate that cimetidine, an immuno-enhancing agent, can increase the response to phenytoin, a positive reference compound in the PLN assay. Thus, in addition to predicting those drugs with the capacity to induce GvH-like reactions and investigating the mechanism involved, the PLN assay may also prove useful in the pre-clinical assessment of immunomodulating agents. PMID- 1426651 TI - Assessment of the anti-viral effect of a short-term oral treatment of mice with live Saccharomyces cerevisiae cells. AB - For assessing the efficacy of antiviral treatments, influenza and herpes virus HSV-1 infections of varying degrees of severity have been produced. The infections proved to be reproducible with respect to both their course and death rate. These infections also exhibited a course slow enough to permit the assessment of treatments under conditions mimicking human infections and lent themselves to the choice of the best adapted strategy to treat an infection. A short-term oral treatment with live cells of S. cerevisiae was efficacious in protecting mice against mild influenza infection and partly but significantly against severe infection. On the other hand, it did not afford significant protection towards either mild or severe HSV-1 infections, but it significantly potentiated the effectiveness of the antiviral drug vidarabin. S. cerevisiae treatment induced the synthesis of IFN alpha but not that of TNF alpha. PMID- 1426652 TI - Protodyne: an immunostimulatory protein component, prepared from gram-positive Bacillus subtilis. AB - A protein component derived from bacterial protoplasm, called Protodyne, increases the non-specific resistance to infections by bacteria and viruses. Here we show that Protodyne can be prepared not only from Gram-negative bacteria, but also from Gram-positive bacilli. Several preparations of Protodyne, prepared from Bacillus subtilis by phenol extraction or by ammonium sulfate precipitation, were evaluated for immunomodulatory activities in a variety of assays. Protodyne had a marked mitogenic activity on mouse spleen cells; it was a potent inducer of tumor necrosis factor (TNF) and stimulated production of interleukin-1 (IL-1) in human peripheral blood mononuclear cells; it increased the capacity of activated macrophages to undergo a respiratory burst, to produce intracellular killing of leishmanial parasite and extracellular lysis of mastocytoma cells; it also stimulated phagocytosis of latex particles, and prolonged survival of immunosuppressed mice infected with Pseudomonas aeruginosa. These activities were not inhibited by polymyxin B, indicating that the activity of Protodyne is not the result of contamination with exogenous lipopolysaccharide. It appears that Protodyne exerts its many immunomodulatory actions by inducing the release of soluble mediators, including TNF and IL-1. PMID- 1426654 TI - Standardized mouse infection models as a way of evaluating the potency of anti infectious agents. AB - Standardized bacterial and viral mouse infection models have been developed. Infections with extracellular bacteria (K. pneumoniae, S. pneumoniae, S. pyogenes A) were produced by either of two routes: via the intravenous route (i.v.) resulting in septicaemia and the intranasal route (i.n.) giving infections confined to the respiratory apparatus. Infections with intracellular bacteria (L. monocytogenes, S. typhimurium) were produced only by the i.v. route. Two types of viral infection, mild and severe, were produced. Infection with influenza virus was by aerosol and herpes virus HSV-1 by the intraperitoneal route. All infection models produced under strictly controlled conditions were shown to be characterized by a remarkable reproducibility regarding both the pattern of development and death rate. The infection models lend themselves to estimation of the efficacy of a drug as well as the designing of new therapeutic strategies. PMID- 1426653 TI - A sequential multi-assay protocol for the preclinical assessment of natural product complex carbohydrate immunomodulators. AB - A major barrier to the understanding, development and utilization of natural product complex carbohydrate immunomodulators has been the lack of standardization during pre-clinical efficacy and safety testing. In addition, it has been our experience that no single assay system or model is adequate for assessing preclinical efficacy and safety of these agents. To address these important issues, our laboratory group has developed a sequential multi-assay protocol for the preclinical evaluation of natural product complex carbohydrate immunomodulators. This sequential multi-assay screening protocol is divided into four phases: 1) physiochemical characterization of the carbohydrate polymer; 2) evaluation of immune stimulatory activity; 3) assessing in vivo anti-microbial activity and anti-tumor efficacy and 4) preclinical safety evaluation. This sequential protocol provides an effective, reproducible and rational approach to the preclinical assessment of complex carbohydrate immunomodulators that, in our experience, is predictive of clinical safety and efficacy. PMID- 1426655 TI - Ex vivo and in vivo characterization of biological response modifiers (BRMs). PMID- 1426656 TI - Evaluation of clinical trials of immunomodulators for prevention of recurrent respiratory infections in children. AB - Despite numerous clinical studies showing "significant differences" in favour of immunomodulators versus placebo in the treatment and/or prevention of recurrent respiratory tract infections, the efficiency of such treatments is still not readily acknowledged by a large part of the medical profession nor by governmental authorities in several countries. In an effort to analyze the causes of this scepticism we performed a retrospective study of 15 clinical trials, using a series of quality assessment criteria. From the results of our analysis we propose a series of recommendations for improving the quality of clinical trials with immunomodulators. Furthermore, in order to avoid suspicion of a publication bias, we recommend setting up a registry of all ongoing clinical studies with immunomodulators. PMID- 1426657 TI - Immunomodulators and primary prevention of respiratory infections: methodological considerations. AB - Immunomodulators have been evaluated mainly for their efficacy as a secondary preventive treatment to protect sick children from the recurrence of infections. We investigated the efficacy of one such product, IMOCURR, as a primary preventive treatment in children attending daycare, who face a very high risk of recurrent infections. EPICUR is a double-blind trial which was designed to study the efficacy of IMOCURR versus placebo. In order to have sufficient statistical power, data collection was based on a daily follow-up procedure and all important concomitant risk factors, such as age, environment and season, were controlled at the study design stage. The sample size required was calculated to be at least 400 children and a total of 423 were actually included. The results obtained for the total follow-up period and those obtained for the treatment period only were very different. This finding raises important questions which have methodological implications. This paper discusses these implications. PMID- 1426658 TI - Prediction of pulmonary immunodeficiency in chronic bronchitis by cutaneous hypoergy to multitest. AB - Multitest (Pasteur Merieux) is a plastic disposable device used to assess delayed cutaneous hypersensitivity (DCH) to seven antigens. Hypoergy to Multitest is believed to reflect a status of compromised cell-mediated immunity. Among the many possible pathogenic factors of chronic bronchitis, immunodepression has been little investigated. Indeed, whether lower immunodefence is the cause or the consequence of chronic bronchitis is still a subject of debate. The aim of the study was to evaluate DCH in a large group of patients with chronic obstructive pulmonary disease (COPD) and in a control group, in order to relate DCH (expressed as score, mm) to clinical and functional impairment. One hundred patients with COPD in stable conditions and not undergoing treatment with immunomodulating drugs (mean age, yr, M +/- SD: 66.1 +/- 6.5) and 40 normal controls in the same age range were admitted to the study. Evaluated parameters were: symptoms scores, physical examination, lung function tests and Multitest. Fifty-three percent of the COPD patients were hypoergic compared with 14% of controls. The Multitest score was 10 +/- 10 (mm M +/- SD) in COPD compared with 17 +/- 9 in controls. The Multitest score was significantly related to age (r = 0.45) in the control group, but not in COPD patients. DCH to only three of the seven antigens may predict a response to Multitest, with a sensitivity of 90%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426659 TI - Immunotherapeutic strategies for neoplasia. PMID- 1426660 TI - Peripheral blood specific antibody-forming cells after oral stimulation with a ribosomal vaccine. AB - A double-blind study was performed in 12 healthy volunteers in order to determine whether circulating immunocytes are present after oral immunization. Sequential samples of peripheral blood were collected at various times after ingestion of a ribosome vaccine (D53) or placebo. Immunoglobulin-containing cells were identified in immunofluorescence and specific antibody-forming cells were detected in agarose ELISA-spot. Higher numbers of both types of cells were observed in the group of individuals receiving ribosomal extracts. An open study allowed a better approach to the kinetics of this phenomenon, related to the release of activated B-cells from Peyer's patches upon antigenic stimulation. This methodological approach has been described in animal models but seldom reported in humans. PMID- 1426661 TI - Immunostimulant effects on granulocyte functions during an acute respiratory infection. AB - Treatment of healthy volunteers by Ribomunyl, whether or not in association with in vitro antibiotics (amoxicillin or josamycin), has been earlier demonstrated to be an efficient stimulant of PMN functions (adhesion and migration). This second double-blind study versus placebo was performed on 17 patients with acute respiratory infections (placebo group: eight subjects; Ribomunyl group: nine subjects). Ribomunyl treatment (four days) associated with antibiotherapy (amoxicillin) induced a significant increase of PMN adhesion (p = 0.014) with no significant effect of the placebo (p = 0.30) and no significant difference between the initial level of PMN adhesion of the two groups (placebo-Ribomunyl). PMID- 1426662 TI - Recent progress in immunopharmacology and therapeutic effects of polysaccharides. AB - Lentinan, a (1----3)-beta-D-glucan with (1----6)-beta-D-glucopyranoside branches and its related polysaccharides have marked antitumour activity in allogeneic, syngeneic and autochthonous primary hosts, suppress chemical and viral oncogenesis, and prevent cancer recurrence or metastasis after surgery. Results of the clinical application of lentinan have proven prolongation of life-span of the patients with advanced and recurrent stomach, colorectal and breast cancer with only little toxic side effect. These polysaccharides also increase host resistance to various kinds of bacterial, viral and parasitic infections including AIDS. Lentinan appears to represent Host Defence Potentiators (HDPs), which can restore or augment the ability of responsiveness of the host to lympho cytokines or other intrinsic bioactive factors through maturation, differentiation or proliferation of the important cells for host defence mechanisms. That is, HDPs might make the physiological constitution highly cancer and infection-resistant, which may be a concept in Oriental Medicine, the fundamental principle of which is to regulate homeostasis of the whole body and to bring the diseased person to his normal state. HDPs such as lentinan are the most appropriate drugs to prevent cancer recurrence, or the manifestation of AIDS symptoms in HIV carriers. PMID- 1426663 TI - Long-term immunobiological effects of intravesical bacillus Calmette-Guerin against bladder carcinoma recurrences. AB - Intravesical bacillus Calmette-Guerin is a highly effective therapy against superficial bladder cancer recurrences and urothelial carcinoma in situ, the antitumoral effects of which seem to be linked to immunological effector mechanisms. To characterize further these mechanisms which contribute to the long term effectiveness of BCG therapy, the local mononuclear cell subsets as well as the local cytokine production were assessed in the bladder wall of patients receiving intravesical BCG immunotherapy with special regard to long-term persisting changes, using immuno-enzymatical staining methods. All patients exhibited a significant increase after BCG in the local mononuclear cell population, with a predominance of the helper T-cell subset. Immunocompetent cells expressed activation markers for a prolonged period. Furthermore, a significant increase in the local cytokine production after the initial course of BCG was demonstrable, which persisted even after 12 to 21 months. These changes suggest that the BCG-induced activation of the local immune system persists over a long period after an initial course of intravesical therapy. PMID- 1426664 TI - Standardized viability test required for preventive, immunomodulator and recombinant BCG vaccine. AB - The protective and immunostimulating effect of the living attenuated BCG vaccine cannot be expressed by bacterial mass (mg/dose). Colony forming units (CFU 10(6)/ml) and 95% confidence limit estimates as precise in vitro potency tests are required for the exact evaluation of the immunogenicity and reactogenicity of the BCG vaccine. The laboratory technique and computerized statistical analysis presented here ensure the precision and validity of the BCG viability test, permit the standardized BCG CFU 10(6)/ml unbiased point and confidence interval estimation for preventive and immunomodulator administration of the BCG vaccines and the evaluation of the genetic transformation frequency in recombinant BCG experiments. PMID- 1426665 TI - Stability of BCG vaccine (intravesical) Theracys/BCG therapeutic ImmuCyst and its importance in clinical efficacy. AB - The manufacture of Therapeutic BCG can and should be a controlled process, to ensure adequate treatment doses are received by CIS patients. Standardization of production methods and CFU potency testing methods are essential to ensure continued successful treatment of CIS. Stability data can be used to validate assumptions about Therapeutic BCG potency used in clinical trials. Accelerated heat degradation studies of Therapeutic BCG should not be used for predictions of shelf life, but can be used for comparative purposes. PMID- 1426666 TI - Standardization of BCG multiple puncture 40 mg and BCG live (intravesical) Theracys/BCG therapeutic Immucyst. PMID- 1426667 TI - Evaluation of clinical data in bladder cancer immunotherapy with Connaught BCG (ImmuCyst). AB - Treatment of superficial bladder carcinoma in situ with Connaught BCG (ImmuCyst) significantly increased complete response rate and extended the disease-free interval when compared with Doxorubicin (DOX) chemotherapy. In 54 patients treated with ImmuCyst, 74% showed complete response compared with 42% of 60 patients treated with DOX. The median disease-free time was 48.2 months for BCG and 5.9 months for DOX treatment. Types and severity of adverse reactions were similar for both treatments and within tolerable ranges. PMID- 1426668 TI - Overall evaluation of immunomodulators. PMID- 1426669 TI - How can we stimulate the immune system in vivo? PMID- 1426670 TI - Immunomodulators. PMID- 1426671 TI - Oral administration of immunomodulators and the mucosal immune system. AB - Orally administered antigens reach the lymphoid tissue in Peyer's patches in the gut where they initiate an immune response with clonal expansion of antigen specific T and B cells. Activated T cells migrate through lymph and blood to intestinal epithelium (intra-epithelial leukocytes) whereas activated B cells migrate to the lamina propria, other mucosae and exocrine glands where they differentiate into plasma cells secreting polymeric IgA1 or IgA2. These antibodies are transported across the epithelial cells after binding to a poly-Ig receptor, then excreted in the lumen as secretory IgA. Reciprocal interactions have been demonstrated between lymphoid and epithelial cells in the mucosae. Oral administration of antigens in different experimental models may induce the production of secretory antibodies and/or systemic unresponsiveness with suppression of delayed-type hypersensitivity or specific IgG and IgE antibody production or both. New strategies are currently being explored for the development of oral vaccines using recombinant antigens or viral vectors (e.g. pox-viruses, vaccinia virus, cholera toxin B subunit etc.). Conversely, immunomodulating compounds or procedures which could enhance specific oral tolerance in association with antigen would have considerable therapeutic applications in auto-immune diseases and allergy. PMID- 1426672 TI - Synthetic lipopeptide immunomodulators derived from bacterial lipoprotein: tools for the standardization of in vitro assays. AB - For the evaluation of immunomodulators by in vitro assays, agents working reproducibly are difficult to obtain; conventional preparations of bacterial immunomodulators tend to vary for different preparations. Here we suggest that synthetic lipopeptide analogues derived from bacterial lipoprotein can be used as standards for various in vitro assays: studying B lymphocyte activation, lipopeptides act as potent mitogens and polyclonal activators inducing immunoglobulin synthesis. In monocytes/macrophages, lipopeptide stimulate the secretion of IL-1, IL-6, tumor necrosis factor (TNF) and nitrogen oxide (NO); they also induce tumor cytotoxicity. Lipopeptides also constitute potent immuno adjuvants in vitro and in vivo, either in combination with or covalently bound to antigen. These activities are displayed in various species; in mice they are found in LPS non-responder and responder strains. The novel synthetic lipopeptides described here can be synthesized readily in gram amounts with high purity and reproducibility; they are non-toxic and can be stored for a long time even at room temperature. Thus, lipopeptides meet the requirements to serve as effective standards for a multitude of relevant biological assays. PMID- 1426673 TI - Classification of immunotherapeutic agents. PMID- 1426674 TI - IMOCUR stimulates production of immunoglobulins; preliminary results concerning a correlation between in vitro and in vivo experiments. AB - The bacterial extract IMOCUR is described as an in vivo stimulant of antibody production during animal testing and human clinical trials. Using a slightly modified procedure (13) dealing with in vitro immunoglobulin production by C57B1/6 mouse spleen cells, we have shown that IMOCUR potentiates spontaneous IgM production. In order to explore the putative relation between this in vitro activity and the current in vivo control test (stimulation of plaque-forming cell production after sheep red blood cell injection to Balb/c mouse), we have assayed 10 lyophilisates in vitro and in vivo before and after heat inactivation (80 degrees C, 7 days in a saturated water atmosphere). Results have shown that this treatment inhibits, respectively, totally and partially in vivo and in vitro activities. Thus the in vitro technique seems to be appropriate for the control of activity of the various batches of IMOCUR. Experiments are under way to clarify the mathematical correlation which may exist between the in vitro and in vivo experiments. PMID- 1426676 TI - In vitro analysis of immunomodulators. PMID- 1426675 TI - C-fos and c-myc modulation, mitogenic effect and Ia expression in the P388D1 murine macrophage line treated by immunomodifiers. AB - The aim of the present study was to investigate whether the early modulation of the c-fos and c-myc oncogenes could give some orientation to the impact of immunomodulators on the monocyte-macrophage lineage. In order to work in a homogeneous system we used the P388D1 mouse macrophage cell-line which is considered as an almost mature macrophage. When P388D1 cells were stimulated by LPS, interferon-gamma or the association of both compounds, no direct correlation could be found between the modulation of DNA synthesis and the early expression of the c-fos and c-myc oncogenes. The positive regulation of Ia antigen expression seemed to correlate with the absence of induction of c-fos oncogene. PMID- 1426677 TI - Immunotoxicology of immunomodulators. AB - Immunotoxicology is the study of the immune system as a target organ for the toxicity of drugs and chemicals. As immunotoxicologists focused most of their interest on immunosuppression, the toxic consequences of immunomodulation are less clearly established. However, a number of immunopharmacologically-mediated side-effects including influenza-like symptoms, exacerbation of underlying diseases, e.g. autoimmune diseases, increase in hypersensitivity reactions against unrelated antigens and inhibition of hepatic drug metabolism have been described and may be used as a basis for further safety evaluation. Current pre clinical assessment of immunotoxicity is usually performed in the rat during sub chronic testing. The relevance of these protocols as far as immunomodulators are concerned is unknown. Careful attention should be paid to safety pharmacology testing, e.g. cytokine release, effects on animal models of auto-immune and hypersensitivity reactions, and hepatic drug metabolism. The role of post marketing drug surveillance should also be emphasized. Advances in our understanding of the mechanism(s) of immunomodulation together with the development of more active immunomodulators are expected to improve the current pre-clinical safety assessment of these compounds. PMID- 1426678 TI - 18q- chromosomal abnormality in a phenotypically normal 2 1/2-year-old male with autism. AB - The authors report the case of a 2 1/2-year-old male with autism, with an 18q- chromosomal abnormality in the absence of phenotypical features of the 18q- syndrome. It is suggested that clinicians evaluating children with autistic disorders consider obtaining chromosome analysis, even in the absence of phenotypical abnormalities. PMID- 1426679 TI - Is the cure worse than the disease? Caveats in the move from laboratory to clinic. PMID- 1426680 TI - Drug management of epilepsy. PMID- 1426681 TI - Mother and daughter with Rett syndrome. PMID- 1426682 TI - Microcephaly and intelligence re-examined. PMID- 1426683 TI - The cost of ignorance. PMID- 1426684 TI - Effect of abuse and neglect on the development of children's speech and language. PMID- 1426685 TI - Peripheral and central mechanisms of hindfoot equinus in childhood hemiplegia. AB - A detailed clinical examination of 24 hemiplegic children at a mean age of 9.9 years showed that nine had an obligate toe-strike when walking at a self-selected speed and this was maintained throughout stance. None of the 24 children had a fixed equinus. No association could be found between this pattern of gait equinus and lower-limb atrophy, reduced ankle-joint range, muscle extensibilite, power of dorsiflexors and plantarflexors or actual muscle imbalance at the ankle joint. Gait equinus was independent of reduced compliance of the calf muscles, of a clinical diagnosis of tonic spasticity, of fine-motor dexterity of the toes, and of the side of the hemiplegia. Gait equinus cannot be explained merely in terms of a central paralytic foot-drop. A developmental model of equinus is advanced. PMID- 1426686 TI - Calf-tendon jerks are altered in congenital equinovarus deformity. AB - Stretch reflexes of posterior tibial (PT) and triceps surae (TS) muscles were studied electrophysiologically in 27 children with unoperated unilateral congenital equinovarus deformity, in an attempt to evaluate changes in tone of the leg muscles as a possible pathogenetic factor. Significantly reduced latency of the PT responses on the affected side was recorded in a majority of patients. In most patients the amplitudes of the PT responses were asymmetrical; however, lateralization was inconsistent. The TS responses were asymmetrical in a smaller proportion of the patients, though still significantly different from the controls. The findings suggest an asymmetrical increase in excitability level of the PT motoneuron pool on the affected side. PMID- 1426687 TI - The offspring of people with cerebral palsy. AB - To test a hypothesis that a placental deficit as a possible cause of CP might be transmitted, 88 people with congenital CP were contacted by questionnaire and letters. They had had 122 children, 93 per cent of whom were reported to be normal. The frequency of miscarriages and toxaemia was normal. 5 per cent of the mothers had had emergency caesarean sections. Three mothers also had minor malformations. The mean gestational age of the children was 38.8 weeks and their mean birthweight was 3295g. The mean birthweight of the mothers born preterm was 984g and that of their babies was 3244g. Two of the 122 children had diplegia, four had malformations, one had trisomy 18 and there was one stillbirth. PMID- 1426688 TI - Care-load for children and young adults with severe cerebral palsy. AB - Care-load was analysed for 44 children and young adults (mean age 18.9 years) with severe spastic quadriplegia. All were enrolled in a residential school/hospital and used wheelchairs. The majority were in the moderate to borderline range of mental retardation. They were monitored for 24 hours a day over a seven-day period, and were timed in 10 major activities, including basic care (bathing, toileting, dressing, grooming, feeding), as well as sleep, leisure, education/vocation, counseling/psychosocial therapy, medical/nursing care, transportation, and at home. The findings replicated those of an earlier Swedish study, which suggests that the basic care needs of individuals with severe cerebral palsy may be predictable, regardless of the type of care being provided. PMID- 1426689 TI - Technical aids for daily activities: a regional survey of 204 disabled children. AB - Home-care of even severely disabled children is strongly favoured today. However, the role of technical aids for daily activities has not been emphasised in the assessment of the needs of families with disabled children. This study evaluated the extent of help needed for daily living among 204 disabled children and the uses and role of and need for technical aids for eating, dressing, toileting and bathing. The children needed much help. Severely disabled children and their parents benefited most from the use of aids. The structured interview unexpectedly revealed many problems, including a considerable need for extra aids for dressing, bathing and toileting. The parents were ready to accept technical aids, but needed more information on their possibilities, benefits and therapeutic aspects. The authors conclude that the need for technical aids for daily activities is not readily recognised during outpatient or hospital visits. PMID- 1426690 TI - Goldenhar syndrome and autistic behaviour. AB - Two girls with concomitant Goldenhar syndrome (oculo-auriculovertebral spectrum disorder) and autistic disorder are described. One was diagnosed as having Goldenhar syndrome in the first few weeks of life and as having autistic disorder in her fifth year; the other was diagnosed as having Goldenhar syndrome when she was referred for evaluation of autistic symptoms at seven years of age. The type of physical abnormalities encountered in Goldenhar syndrome suggests damage to neural structures in the second or late stages of the first trimester. The two cases described in this report suggest that autistic disorder sometimes can result from neural damage during the second trimester. PMID- 1426691 TI - Is a fluoroscopic verification of the electrode position necessary in ambulatory intragastric pH monitoring? AB - To assess whether a fluoroscopic verification of the electrode position is necessary before and whether electrode displacement occurs during intragastric pH measurements, a crossover study was performed in 20 healthy male volunteers. The pH electrode was initially placed in the gastric corpus using pH readings and catheter length only, and the electrode tip was fluoroscopically located before and after the 24-hour study. Only in one study arm was an adjustment of the electrode position allowed, if fluoroscopy showed a position outside the gastric body. Thirty-seven (92%) of all 40 electrodes were in the corpus when placed by pH-metric methods alone. With fluoroscopic guidance, 2 of the 3 electrodes lying outside the corpus could be repositioned as desired. The median night, day or 24 hour gastric pHs measured in the groups with or without replacement of the electrode tip were identical. Displacement after 24-hour measurements did not occur with initially correctly positioned electrodes. Fluoroscopy is not necessary for the verification of the position of electrodes placed by pH-metric techniques in individuals with residual acid secretion, and electrode displacement is rare. PMID- 1426692 TI - Functional and structural changes in the jejunum of the rat following cysteamine and stress-induced duodenal ulcer. AB - The effects of cysteamine and stress-induced duodenal ulcer on the functional and structural properties of the rat jejunum were investigated. The absorptive capacity of the jejunum was determined using alanine as the permeant solute and the single-pass perfusion technique. A statistically significant decrease (p < 0.01) in alanine absorption was observed after 8 h and 3 days of duodenal ulcer induction by stress and cysteamine respectively. However, alanine transport measured 7 days after cysteamine or stress ulcer induction showed no significant change from control values. Cysteamine and stress-induced duodenal ulcer did not show any significant change in water absorption across the jejunum when measured after 8 h, 3 and 7 days of ulcer induction. Microscopically, the jejunum of rats with 3-day cysteamine-induced ulcer exhibited diffuse type of apical derangements with excessive swelling of the villi and progressive degenerative changes. No such changes were noticed on the 7th day nor in the jejunum of the rats with stress-induced duodenal ulcer. The results suggest that cysteamine-induced duodenal ulcer produces an inhibition in the absorptive capacity of the jejunum which is time-dependent and reversible. PMID- 1426693 TI - Continuous monitoring of sodium ion concentration in the human stomach--a new technique for the detection of duodenogastric reflux. AB - Measurement of sodium ion concentration in gastric juice offers a simple means of detecting duodenogastric reflux (DGR). Using aspirated gastric juice, we measured sodium ion concentration, bile acid levels and phospholipase A2 activity and found that sodium ion levels increase along with these other standard markers during DGR. Following this, using a sodium ion selective electrode and a portable data logger, continuous recordings of sodium ion concentration were made in the human stomach. These studies demonstrated the ability of sodium ion monitoring to detect major DGR episodes in the body of the stomach. PMID- 1426694 TI - Cellular immune responses of peripheral blood mononuclear cells to HBV antigens during chronic and acute HBV infection. AB - Patients with acute self-limited and chronic HBV infection were studied to determine their in vitro cellular immune response to HBV antigens. In interferon gamma production cultures which were evaluated as an indicator of cellular immune response, peripheral blood mononuclear cells from patients with HBeAg-positive chronic hepatitis showed elevated response to HBcAg, while those from HBeAg positive asymptomatic carriers revealed no response to either HBcAg or HBeAg. HBeAg-stimulated interferon-gamma production was higher in anti-HBe-positive chronic hepatitis and asymptomatic carriers than that in HBeAg-positive patients. Interferon-gamma production against HBcAg was shown to be HLA class II restricted by blocking assay using monoclonal antibodies. HBsAg with or without pre-S2 did not amplify interferon-gamma production of patients with chronic hepatitis. In acute hepatitis B, both envelope and nucleocapsid antigens induced greater interferon-gamma production than in chronic HBV carriers. These results indicate that the patients with acute hepatitis responded more to HBV antigens compared with chronic HBV carriers. Furthermore, enhanced cellular immune responses, particularly to HBeAg, were observed in anti-HBe-positive patients compared to HBeAg-positive patients during chronic HBV infection, suggesting that the poor response to HBeAg in HBeAg-positive patients may account for the failure to clear HBV. PMID- 1426695 TI - Low incidence of ulcerative colitis and proctitis in Bangladeshi migrants in Britain. AB - To assess the incidence of ulcerative colitis and proctitis in a defined migrant population, a retrospective, epidemiological community study was performed in the London Borough of Tower Hamlets from 1972 to 1989. The population of 164,000 includes 28,000 Bangladeshis. Potential cases were identified from hospital departments of pathology and medical records. There were 107 cases of ulcerative colitis in Europeans and 5 in Bangladeshis. There were 74 and 2 cases of proctitis in these communities, respectively. The mean standardised incidence of ulcerative colitis in Bangladeshis (1.8 cases/10(5)/year) was marginally lower than in Europeans (6.2 cases/10(5)/year, Z = 0.7, n.s.). The mean standardised incidence of proctitis in Bangladeshis was 0.6 cases/10(5)/year and in Europeans 3.2 cases/10(5)/year (Z = 0.6 n.s.). Anatomical extent of colitis was similar in all ethnic communities, although complications were less likely in minority groups. These findings suggest that the incidence of ulcerative colitis and proctitis in Bangladeshis, in Britain, is amongst the lowest in the world. PMID- 1426697 TI - Effects of ethanol and wine on hepatic arterial and portal venous flows in conscious dogs. AB - The effects of ethanol and wine on hepatic arterial and portal venous flows were examined in conscious dogs. Ethanol was given intravenously or intragastrically, and red wine (ethanol: 14%) was given intragastrically over 30 min. Intravenous ethanol (0.8 g/kg) and intragastric ethanol (14% vol/vol) increased hepatic arterial flow, which remained elevated for 60 min after the cessation of ethanol administration. Ethanol also increased portal venous flow. Portal venous flow returned gradually toward basal levels after the cessation of intravenous ethanol infusion, whereas it remained elevated even after the cessation of intragastric ethanol. Intragastric wine increased hepatic arterial and portal venous flows. In contrast to intragastric ethanol, hepatic arterial flow continued to rise after the cessation of intragastric wine infusion, while portal venous flow returned toward basal levels. We conclude that, though both ethanol and wine increase hepatic blood flow, the responses of hepatic arterial and portal venous flows differ substantially among intravenous ethanol, intragastric ethanol and intragastric wine. PMID- 1426696 TI - Fat and gastric acid secretion. AB - To evaluate the importance of the terminal carboxyl group of the oleic acid molecule in the inhibition of gastric acid secretion, 6 normal persons were stimulated twice with duodenal perfusates containing either 20 mM oleic acid or 20 mM oleyl alcohol. Oleic acid significantly inhibited the gastric acid secretion stimulated by pentagastrin (100 ng/kg/h) and increased the levels of secretin in plasma. The effect of oleyl alcohol was insignificant. It is concluded that the carboxyl group of the fat molecule has an important role in the inhibition of gastric acid secretion, and the effect could in part be attributable to the release of secretin into plasma. PMID- 1426698 TI - Sonographic imaging of extracorporeal shock wave effects in the liver and gallbladder of dogs. AB - During extracorporeal shock wave lithotripsy, changes in tissue echogenicity are observed by ultrasound. Their significance is not known. An experiment was performed in which 3,000 extracorporeal shock waves were applied under sonographic observation to the gallbladder wall of 6 dogs. No stones had been implanted, but transient shadows appeared simulating jumping stone fragments in the bladder. Echoes within the bladder lumen occurred in 3 dogs and were associated with hemorrhage into the lumen; in an additional ex vivo experiment, shock waves generated echoes in bile only after injection of a small amount of blood. In the liver, a transient increase in echogenicity was noted after a few shocks; it coincided with the region of tissue damage. Intense focal echoes occurred in the liver of 2 dogs at sites where a hematoma was found at autopsy. It is concluded that an increased focal echogenicity is an indicator of tissue damage by shock waves. The sonographic changes are thought to be caused by the transient generation of gas bubbles. The interaction of shock waves with gas bubbles is an established powerful mechanism which could explain the generation of tissue damage by shock waves. PMID- 1426699 TI - Increased luminal release of hyaluronan in uninvolved jejunum in active Crohn's disease but not in inactive disease or in relatives. AB - Recently obtained data suggest that there is a subclinic inflammatory activity in the apparently uninvolved intestinal mucosa in Crohn's disease (CD). As CD is characterized by an activation of connective tissue and fibrosis, we investigated the extent to which hyaluronan (HA), an essential component of the connective tissue, was released into the lumen of an isolated jejunal segment in CD patients and in relatives. Patients with active CD of the terminal ileum (CD activity index, CDAI, > 150; n = 14), patients with CD in remission (CDAI < 150 n = 10), first-degree relatives of the CD patients (n = 21) and healthy controls (n = 43) were orally intubated with a catheter allowing occlusion and perfusion of a segment of the proximal jejunum. The jejunal fluid concentration of HA was 65 +/- 45 micrograms/l in patients with active CD in the terminal ileum, significantly higher than the value for 43 healthy controls (42 +/- 23 micrograms/l; p < 0.05), and the corresponding values for patients in remission (42 +/- 23 micrograms/l) and for first-degree relatives of the CD patients (53 +/- 52 micrograms/l), were not increased compared to the control group. To localize HA in the tissue, small bowel biopsies were taken during surgery from patients with CD and from controls and affinity stained for HA. There was an intense staining for HA in the lamina propria of the villi, both in biopsies from patients with CD and from controls, but no staining in the epithelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426700 TI - Severe exacerbation of chronic active hepatitis B during interferon alpha therapy. AB - The case of a 52-year-old male with chronic active type B hepatitis in whom severe exacerbation of liver disease was associated with interferon alpha treatment is described. It seems that patients with very active forms of chronic hepatitis B may experience severe and symptomatic exacerbation of liver disease during interferon treatment. PMID- 1426701 TI - The location and expression of fibroblast growth factor (FGF) in F9 visceral and parietal embryonic cells after retinoic acid-induced differentiation. AB - It is well-established that fibroblast growth factors (FGFs) participate in mesoderm formation and patterning in the developing embryo. To identify cells in mammalian embryos that produce and/or respond to FGFs, we utilized the F9 teratocarcinoma cell system. Undifferentiated F9 cells resemble inner cell mass (ICM) cells of the mouse blastocyst by several criteria including having a characteristic high nuclear to cytoplasmic ratio and by their expression of stage specific embryonic antigens. F9 stem cells differ from ICM cells by their low spontaneous rate of differentiation and their differentiation potential. ICM cells are heterogeneous with a proportion of the cells maintaining totipotency. In contrast, F9 stem cells appear capable of forming only endodermal derivatives. Retinoic acid (RA) treatment of F9 stem cells is required for them to differentiate, and under different culturing conditions the F9 cells will form either extraembryonic parietal or visceral endoderm. We have previously shown that FGF is synthesized by F9 parietal endoderm, but not by F9 stem cells. Our present study demonstrates that F9 aggregate cultures that contain visceral endoderm cells produce cell-associated-heparin-binding mitogens for 3T3 and endothelial cells, factors with characteristics of FGFs. Furthermore, our studies detect endothelial cell-mitogens within the extracellular matrix (ECM) of F9 parietal endoderm cells, not detected within F9 stem cell 'matrices'. Parietal endoderm cell matrix mitogens could be removed by prior treatment of the ECM with buffers containing heparin or 2 M NaCl, and could be neutralized by basic FGF antibodies. PMID- 1426702 TI - The influence of type I collagen on the growth and differentiation of the human colonic adenocarcinoma cell line HT-29 in vitro. AB - HT-29 Human colonic adenocarcinoma cells when grown on a plastic substratum were anaplastic in appearance and failed to express any morphological or biochemical features that were characteristic of intestinal differentiation. Growth of HT-29 cells subcutaneously in the flank of immune deprived mice gave rise to morphologically heterogeneous tumors which were poorly differentiated but contained approximately 11% of cells with an intestinal phenotype: these showed features typical of cell polarization with well-developed microvilli, tight junctional complexes and desmosomes between adjacent cells. The transfer of cells from plastic onto either a fixed (designated 'non-released') or floating (designated 'released') type I collagen gel induced some morphological features typical of intestinal differentiation; for example goblet-like cells were observed after 9 days, but biochemical markers of differentiation were expressed only modestly. The continued subculture of HT-29 cells on collagen type I gels, which were either attached to the plastic or floating in the medium, induced some morphological features of intestinal differentiation and changes in the activity of brush border-associated enzymes. Alkaline phosphatase activity was enhanced from 1.3 x 10(-3) mumoles/mg/min for cells cultured on plastic substrata to 2.1 x 10(-3) mumoles/mg/min when gels were non-released, and 2.9 x 10(-3) mumoles/mg/min when gels were released after 12 days of culture. This was confirmed by electron microscopical visualization of alkaline phosphatase activity. Elevated levels of aminopeptidase activity were also observed on day 12 (plastic = 26 milliunits/mg; non-released gel = 41 milliunits/mg; released gel = 36 milliunits/mg). Similarly, changes occurred in the secretion of carcinoembryonic antigen from 0.96 x 10(-2) micrograms/mg/48 hours by cells cultured on plastic to 2.3 x 10(-2) micrograms/mg/48 hours by cells cultured on floating collagen gels. The effects of permitting HT-29 cells to undergo polarization were tested by culture on inert filter inserts: morphological features of intestinal differentiation were observed although this did not occur until after 21 days. These studies show that optimization of the growth conditions of anaplastic cells in vitro may provide cultures more representative of the tumor in vivo. This model system may be useful for cell biological and pharmacological studies of colon carcinoma. PMID- 1426703 TI - Examination of the role of the proteolytically-activated form of protein kinase C in the differentiation of human haemopoietic cells. AB - In neutrophils, the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced the translocation of the Ca(++)- and phospholipid-dependent protein kinase, protein kinase C (PK-C) from the soluble to the particulate fraction. At the same time there was a corresponding increase in the amount of Ca(++)- and phospholipid-independent protein kinase activity recovered in the soluble fraction. This soluble Ca(++)- and phospholipid-independent protein kinase presumably reflects proteolytic activation of the particulate associated PK-C. Bone marrow and undifferentiated HL-60 cells also translocated PK-C to the particulate fraction in response to TPA but did not accumulate the soluble Ca(++) and phospholipid-independent form of the enzyme. Similar results were obtained using HL-60 cells induced to differentiate with dimethyl sulphoxide (DMSO), recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) or 1 alpha,25-dihydroxyvitamin D3. There was also no significant change in either the number or time of expression of differentiation-specific cell surface antigens observed on HL-60 cells induced to differentiate with either DMSO, 1 alpha,25-dihydroxyvitamin D3 or TPA in the presence of cyclosporin A, an agent reported to inhibit the proteolytic breakdown of PK-C to the Ca(++)- and phospholipid-independent form. Likewise, cyclosporin A did not affect the rate of extent of differentiation of primary bone marrow cell cultures. These results suggest that the proteolytically activated and phospholipid-independent form of PK-C is probably not involved in haemopoietic cell differentiation. PMID- 1426704 TI - Chemical allergy: molecular mechanisms and practical applications. AB - Allergic reactions can be defined as the adverse, tissue-damaging, and sometimes fatal consequences of specific immune responses, usually to exogenous antigens. In the context of toxicology it is allergic reactions resulting from immune responses to chemicals and drugs which are of greatest relevance. The allergy may take a variety of forms including contact hypersensitivity (allergic contact dermatitis), respiratory hypersensitivity (with symptoms ranging from mild rhinitis to severe asthma), and various types of comparatively ill-defined reactions which in many respects resemble autoimmunity. Of these contact hypersensitivity is the most frequently encountered health problem resulting from the interaction of chemicals with the immune system. A wide variety of chemicals are able to induce contact sensitization. Some of these are, in addition, known to cause respiratory hypersensitivity, a less frequent, but no less important, form of chemical allergy. PMID- 1426705 TI - Further validation of an in vitro method to reduce the need for in vivo studies for measuring the absorption of chemicals through rat skin. AB - Current requirements for the registration of agrochemicals, particularly in the U.S.A., often require the provision of dermal absorption data. In this process the rat is often used and complex in vivo studies, using large numbers of animals, are performed. We have compared the data obtained from in vivo and in vitro dermal absorption studies using eight pesticides with a range of physicochemical properties. Measurements were made of the 14C-labeled pesticides which could be washed from the skin, were associated with (on/in) skin, or absorbed through the skin following dermal applications in vivo and in vitro at various time points over a 24-hr exposure period. Good agreement was found between the amounts washed from and associated with the skin in vivo and in vitro. Over the time period 4-24 hr after application the in vitro experiments predicted the in vivo absorption within a factor of 2-3. These results show that, with a range of pesticide molecules, the in vitro method accurately predicted in vivo absorption supporting the utilization of the in vitro method for risk assessment from exposure to pesticides and other chemicals. PMID- 1426706 TI - A comparative study of the rates of in vitro percutaneous absorption of eight chemicals using rat and human skin. AB - In vitro percutaneous absorption studies were carried out for eight chemicals using full thickness rat skin and human stratum corneum. The purpose of the studies was to compare the rates of absorption for the two species. For each of the chemicals, the observed rate using full thickness rat skin was greater than that observed for human stratum corneum. The ratios of the rates (rat/human) varied from 1.7 to 5.8 with a mean value of 3.1. The chemicals tested were tritiated water, 2-ethoxyethyl acetate, diethylene glycol monobutyl ether, urea, di(2-ethylhexyl) phthalate, 2-ethylhexanol, ethyl 3-ethoxypropionate, and 2 propoxyethanol. The chemicals were chosen to represent a wide range of physical properties and permeability constant values. It was concluded that rat skin was more permeable than human skin for each of these eight chemicals. This conclusion is supported by similar findings from studies in other laboratories and suggests that results from studies in the rat overestimate skin absorption in man. PMID- 1426707 TI - Rate and route of oxidation of acrylic acid to carbon dioxide in rat liver. AB - Results of in vivo metabolism studies with acrylic acid (AA) have indicated that 60-80% of the administered dose is excreted as CO2 within 2-8 hr of oral dosing of rats; however, the pathway of AA metabolism to CO2 in mammals has not been determined. To define this route, rat hepatocytes were isolated and incubated with [1-14C]AA in a sealed vial modified to trap evolved 14CO2. Rapid oxidation of AA to CO2 was observed. Similar incubations conducted with rat liver homogenates fortified with ATP, ADP, coenzyme A, carnitine, and malate also resulted in oxidation of AA. Mitochondria isolated from liver homogenates were incubated with AA under the same conditions and yielded higher rates of AA oxidation than homogenates. Addition of equimolar amounts of propionic acid, 3 hydroxypropionic acid, or 3-mercaptopropionic acid significantly inhibited the oxidation of AA by mitochondria. HPLC analysis of the mitochondrial incubation mixtures indicated that a single major metabolite, which coeluted with 3 hydroxypropionate, accumulated in the solution. The results indicate that AA is rapidly incorporated into a mitochondrial pathway for propionic acid catabolism that results in the release of CO2 and possible bioincorporation as acetate. This pathway appears to be the principal route of detoxification of AA in mammals. PMID- 1426708 TI - The developmental toxicity of 2-ethylhexanoic acid in Wistar rats. AB - The developmental toxicity of 2-ethylhexanoic acid (2-EHA), a wood preservative and a mammalian metabolite of di-(2-ethylhexyl) phthalate was examined in Wistar rats (20-21 pregnant females/dose). Mated animals were exposed to 2-EHA in their drinking water at doses of 100, 300, or 600 mg/kg/day on Days 6-19 of gestation. Control animals received vehicle water. The fetuses were examined (on Gestational Day 20) for external, visceral, and skeletal malformations and variations. 2-EHA was marginally toxic to the dams at 600 mg/kg, but not at lower doses, since the mean near term body weight was reduced by 11%. This dose level was also slightly fetotoxic as indicated by a 5 to 8% decrease in the mean fetal body weight both in males and females. No treatment-related effects were observed in the number of implantations or live fetuses. At doses of 100 mg/kg and above, 2-EHA caused skeletal malformations (clubfoot, absence of fibula, polydactyly), while the development of visceral tissues was less affected. The number of affected fetuses increased in a dose-dependent way (4.9, 8.9, and 15.3% of treated offspring at 100, 300, and 600 mg/kg/day, respectively, vs 2.4% control). These results indicate that 2-EHA is teratogenic in rats already at doses which are not yet maternally toxic. The skeleton appears to be the main target of 2-EHA in developing rats. PMID- 1426709 TI - Carcinogenicity of oral cadmium in the male Wistar (WF/NCr) rat: effect of chronic dietary zinc deficiency. AB - The effect of chronic dietary zinc deficiency on the carcinogenic potential of dietary cadmium was assessed in male Wistar (WF/NCr) rats. Groups (n = 28) of rats were fed diets adequate (60 ppm) or marginally deficient (7 ppm) in zinc and containing cadmium at various levels (0, 25, 50, 100, or 200 ppm). Lesions were assessed over the following 77 weeks. Zinc deficiency alone had no effect on survival, growth, or food consumption. Cadmium treatment did not reduce survival or food consumption and only at the highest doses of cadmium (100 and 200 ppm) was body weight reduced (maximum 17%). The incidence of prostatic proliferative lesions, both hyperplasias and adenomas, was increased over that seen in controls (1.8%) in both zinc-adequate (20%) and zinc-deficient rats (14%) fed 50 ppm cadmium. The overall incidence for prostatic lesions for all cadmium treatment groups was, however, much lower in zinc-deficient rats, possibly because of a marked increase in prostatic atrophy that was associated with reduced zinc intake. Cadmium treatment resulted in an elevated leukemia incidence (maximum 4.8 fold over control) in both zinc-adequate and zinc-deficient groups, although zinc deficiency reduced the potency of cadmium in this respect. Testicular tumors were significantly elevated only in rats receiving 200 ppm cadmium and diets adequate in zinc. Both zinc-deficient and zinc-adequate groups showed significant positive trends for development of testicular neoplasia with increasing cadmium dosage. Thus, oral cadmium exposure is clearly associated with tumors of the prostate, testes, and hematopoietic system in rats, while dietary zinc deficiency has complex, apparently inhibitory, effects on cadmium carcinogenesis by this route. PMID- 1426710 TI - In vivo and in vitro percutaneous absorption and skin evaporation of isofenphos in man. AB - Studies were done to determine the percutaneous absorption of isofenphos in human volunteers from whom informed consent had been obtained. In vivo absorption in man was 3.6 +/- 3.6% of applied dose for 24-hr exposure and 3.6 +/- 0.5% for 72 hr exposure. Skin wash recovery data show that isofenphos evaporates from in vivo skin during the absorption process; the surface dose is minimal (< 1%) by 24 hr. Skin stripping showed no residual isofenphos in stratum corneum. This explains the similar absorption for 24 and 72-hr dose prewash exposures. Skin surface recovery in vivo with soap and water was 61.4 +/- 10.4 for the first dosing time (15 min). Time-recovery response declined with time to 0.5 +/- 0.2% at 24 hr. In vitro absorption utilizing flow-through diffusion methodology with human cadaver skin and human plasma receptor fluid gave 2.5 +/- 2.0% dose absorbed, an amount similar to in vivo studies. An additional 6.5 +/- 24% was recovered in the skin samples (total of 9%). Skin surface wash at 24 hr recovered 79.7 +/- 2.2% and skin content was 6.5 +/- 2.4% (total dose accountability of 88.7 +/- 4.6%). Thus, isofenphos was available for absorption during the whole dosing period. Neither in vitro absorption nor in vitro evaporation studies predicted the potential skin evaporation of isofenphos. Published dermal studies in the rat had predicted isofenphos absorption at 47% of applied dose (12-fold greater than actual in man). Subsequent toxicokinetic modeling predicted possible concern with the use of isofenphos.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426711 TI - Subchronic toxicity of barium chloride dihydrate administered to rats and mice in the drinking water. AB - Barium Chloride dihydrate (BaCl2.2H2O) was given for 92 days to B6C3F1 mice and Fischer 344/N rats in their drinking water at levels of 0, 125, 500, 1000, 2000, and 4000 ppm. The no-effect level for this study was 2000 ppm BaCl2.2H2O in the drinking water. At 4000 ppm, daily consumption for mice was 436 to 562 mg/kg barium, up to four times more chemical than rats. Mortality ranged from 60 to 70% in mice and from 10 to 30% in rats in the 4000 ppm groups. Deaths in mice were associated with a treatment-related renal toxicity. Renal lesions in rats were much less severe than in mice and did not contribute to the treatment-related deaths seen in the high dose group. Body weights of both species and sexes in the 4000 ppm groups were lower than controls at 92 days. Male and female rats in treated groups exhibited higher serum phosphorus than controls. Serum sodium, potassium, and calcium levels in rats were unchanged by barium treatment, as were hematological values. In both species at 4000 ppm, motor activity, grip strength, and thermal sensitivity were marginally affected. These effects were probably secondary changes resulting from BaCl2 toxicity observed at this dose level. In a mating trial, no anatomical effects on offspring of rats or mice were seen. Rats receiving 4000 ppm exhibited marginal reductions in pup weights. No effects were seen on reproductive indices. PMID- 1426712 TI - Investigation of factors influencing urinary porphyrin excretion in rats: strain, gender, and age. AB - Urinary porphyrin excretion rates were evaluated in male rats of the Sprague Dawley, Fischer 344, and Osborne-Mendel strains, and in female Fischer 344 rats, in order to identify an appropriate rat model for long-term studies of chemical induced porphyria. Sprague-Dawley rats displayed a wide interanimal range in total 24-hr porphyrin excretion rates, from 0.9 to 59.6 nmol/24 hr (64-fold). Additionally, individual Sprague-Dawley rats varied by up to 5-fold in total porphyrins excreted from week to week over a 4-week period. Osborne-Mendel rats displayed a 12-fold interanimal difference in 24-hr total porphyrin excretion rates (ranging from 6.2 to 71.1 nmol/24 hr) and up to 4-fold individual variation from 1 week to another. In contrast, rats of the Fischer 344 strain displayed no significant differences in porphyrin excretion rates either among different animals or for individuals from week to week. Determination of individual porphyrin concentrations in the urine demonstrated that inconsistencies in total porphyrin concentration were attributable principally to differences in coproporphyrin concentrations. Frequency analysis of 24-hr coproporphyrin excretion levels among Sprague-Dawley rats demonstrated a widespread range encompassing low levels comparable to those of Fischer rats, high levels similar to those of most Osborne-Mendel rats, as well as intermediate levels. The mean total porphyrin excretion rate among female Fischer 344 rats was 1.2 +/- 0.51 nmol/24 hr, compared to 2.1 +/- 0.50 nmol/24 hr among male Fischer rats. Maturation and aging were found to have little influence on porphyrin excretion rates in male Fischer 344 rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426713 TI - Prenatal dexamethasone exposure in rats: effects of dose, age at exposure, and drug-induced hypophagia on malformations and fetal organ weights. AB - Glucocorticoids cause stunting and cleft palate in rodents. The aim of this study is to identify fetal organs and developmental periods sensitive to stunting induced by maternal exposure to dexamethasone (DEX). DEX (0.2 or 0.4 mg/kg) or saline was given sc to pregnant CD albino rats on Gestation Days (GD) 9-14 or 14 19. On GD 20 dams were euthanized. Fetuses were weighed and examined for cleft palate. Eight fetuses/litter were randomly selected, and weights were obtained. Fetal skeletons were examined for abnormalities, and long bone measurements were taken. A dose-related decrease in maternal and fetal body weights occurred at both exposure periods. Developmental stage-specific malformations were noted in the high-dose group on GD 9-14 (cleft palate) and on GD 14-19 (wavy ribs). A dose response in stunting occurred in all organs except cerebellum in at least one exposure period. Across both exposure periods the brain, heart, testes, and long bones were relatively resistant to DEX. Sensitive organs included thymus, spleen, adrenals, lungs, liver, and kidneys. DEX substantially reduced maternal food intake and increased water intake in some dams. Pair-feeding experiments suggested that the hypophagic effect of DEX was not responsible for the noted malformations and had little impact on growth stunting. The present findings have identified fetal organs, skeletal regions, and developmental periods sensitive to DEX exposure. PMID- 1426714 TI - Immunogenic properties of structurally modified human tissue plasminogen activators in chimpanzees and mice. AB - Immunogenic properties of second generation human tissue plasminogen activator (tPA) derivatives were examined in chimpanzee and mouse systems. Five species of modified tPAs (mtPAs) (designated 2660, 2663, 2810, 8000, and 9200), recombinant native tPA or bovine serum albumin (BSA) as a positive control were subcutaneously injected nine times at suitable intervals into chimpanzees, genetically the closest species to man. These animals were tested for antigen(Ag) specific antibodies to the corresponding proteins by means of enzyme-linked immunosorbent assay and Western blot analysis. Neither 9200, one of the five mtPAs tested, nor tPA was immunogenic, although BSA and the other four mtPAs were immunogenic under these conditions. Thus, an antigenic determinant was not exposed by the modification on 9200 and this modified tPA is expected not to be immunogenic in humans. In the mouse studies, mice were immunized with mtPAs. Serum samples from these animals were tested for antibodies to the mtPAs which did not concomitantly recognize native tPA by immune adsorption of the antibodies to tPA. The amount of such antibodies after the elimination of native tPA reactive antibodies was little or none when the serum samples from 9200 and from the other mtPAs, except 8000, were tested. Taking into consideration the results of the chimpanzee studies, it can be concluded that Ag-specific antibodies are dominantly produced to unchanged epitopes present in modified proteins in the mouse system, in which the native protein is immunogenic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426715 TI - Subchronic toxicity of benzyl selenocyanate and 1,4 phenylenebis(methylene)selenocyanate in F344 rats. AB - Chemopreventive agents benzyl selenocyanate (BSC) and 1,4 phenylenebis(methylene)selenocyanate (p-XSC) were fed in NIH-07 diet to male and female F344 rats (4, 2, and 0.5 mg/kg/day for BSC and 20, 10, and 5 mg/kg/day for p-XSC) for 13 weeks. Weight gains were depressed for male and female rats fed 4 and 2 mg/kg/day BSC, females fed 0.5 mg/kg/day BSC, and male rats fed 20 and 10 mg/kg/day p-XSC. At necropsy, no clear treatment-related lesions were noted, but dose-dependent hepatomegaly was observed in both sexes of BSC and p-XSC groups. Plasma transaminases AST and ALT were elevated in the higher dose groups, while hemoglobin, HCT, and RBC were reduced in most BSC and some p-XSC treatment groups. Plasma glucose was reduced in BSC-treated males. Significant histologic findings included moderate to severe hepatic centrilobular hypertrophy with fatty change in all males and females in the 4 mg/kg/day BSC groups and in 9/15 males and 3/15 females in the 2 mg/kg/day BSC groups. Dose-dependent, mild centrilobular hypertrophy with minimal fatty change was observed in the mid- and low-dose BSC groups and in all p-XSC groups. Mild to moderate renal tubular and interstitial nephritis occurred in the 4 mg/kg/day male BSC group. Dietary maximum tolerated dose levels for chemoprevention studies are 0.5 mg/kg/day (3.0 ppm Se) for BSC and 5 mg/kg/day (32.5 ppm Se) for p-XSC, compared to literature values of 2-3 ppm Se for Na2SeO3. PMID- 1426716 TI - Suppression of the murine gut mucosal IgA response to cholera toxin with oral cyclosporine. AB - The gut mucosal immune system may be a primary target for many ingested chemicals. Methods have been developed to examine the effects of chemicals on the systemic humoral immune response; however, studies to evaluate various methods of assessing the local gut mucosal immune response in a toxicology assay have been limited. The objectives of this study were to examine the effects of the known immunosuppressive compound, cyclosporine (CYS), on the generation of a cholera toxin (CT)-specific gut mucosal IgA response and evaluate the methods used to measure the gut IgA response. Groups of female B6C3F1 mice were left untreated or were treated daily, p.o., with corn oil (vehicle) or CYS at doses of 10 and 50 mg/kg for 20 days. On Days 3 and 13, mice were sensitized p.o. with CT. On Day 21, mice were terminated, gut washings were collected, and lamina propria lymphocytes were extracted from gut tissue with collagenase treatment. Cholera toxin-specific IgA in the gut washings was measured by an ELISA. The numbers of CT-specific IgA (CT-IgA) and total IgA antibody-forming cells (spot-forming cells, SFC) obtained from the lamina propria were determined by the ELISPOT method. A dose of 50 mg/kg CYS produced a significant decrease in the amount of CT-IgA in gut washings. This dose also decreased the number of cells recovered from the lamina propria by at least 50%. The amount of CT-specific SFC/million lamina propria cells decreased with a dose of 10 mg/kg CYS, whereas 50 mg/kg CYS did not alter the response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426717 TI - Interspecies differences in the phagocytic activity of pulmonary macrophages subjected to acidic challenge. AB - Examining interspecies differences in response to ambient pollutants is an essential component of risk assessment. The potential hazard to public health from the inhalation of acid sulfate aerosols is of current concern. A significant biological target is the pulmonary macrophage, which provides a primary defense of the respiratory region of the lungs. One essential function of these cells is phagocytosis of particles. This study assessed the effects of acidic environments on the phagocytic activity of pulmonary macrophages obtained by lavage from humans and three species of laboratory animals commonly used in acid aerosol toxicology studies, namely, rats, rabbits, and guinea pigs. Cells were incubated with polystyrene latex particles in media acidified by addition of sulfuric acid. The percentage of cells which were phagocytic, as well as the relative number of particles ingested by these cells, was found to decrease with increasing acidity for all species. The ranking of response in order of decreasing sensitivity to acidic challenge was as follows: guinea pig > rat > rabbit > human. PMID- 1426718 TI - Comparison of the effects of Wyeth-14,643 in Crl:CD BR and Fisher-344 rats. AB - Wyeth-14,643 (WY) belongs to a diverse class of compounds which have been shown to produce hepatic peroxisome proliferation and hepatocellular carcinoma in rodents. Based on a review of bioassay data, a relationship appears to exist between peroxisome proliferating compounds and Leydig cell adenoma formation. Most rat bioassays with peroxisome proliferators have been conducted in the Fisher-344 (F344) rat, which has a high spontaneous incidence of Leydig cell adenomas. Thus, it was necessary to use an alternative animal model to investigate this relationship further. Therefore the Crl:CD BR (CD) rat, which has a low spontaneous Leydig cell adenoma incidence, was chosen for a 2-year feeding study with WY. Before initiating this 2-year feeding study, it was necessary to investigate whether any strain differences existed between CD and F344 rats with respect to WY-induced peroxisome and cell proliferation. In this study, male CD and F344 rats were fed diets containing 0, 50, or 1000 ppm WY for 21 days. Peroxisome proliferation in the liver and testis was determined biochemically by measuring beta-oxidation activity and was confirmed ultrastructurally. Serum hormone levels and cell proliferation rates in the liver and testis were also measured. In addition, basal beta-oxidation activity and cell proliferation rates were compared between the CD and F344 rats. A significant decrease in final body weight was observed in the 1000 ppm WY groups for both CD and F344 rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426719 TI - Enhanced inflammatory response to acute ozone exposure in rats during pregnancy and lactation. AB - Experimental evidence from several studies suggests that pregnant animals and women are more susceptible to oxidants than nonpregnant controls. In the study reported here, we sought to determine whether pregnant rats are more sensitive than age-matched virgin females to the inflammatory effects of ozone, a gaseous oxidant of considerable environmental significance. Rats at several stages of pregnancy and lactation, as well as age-matched virgin females, were exposed to 1 ppm ozone for 6 hr. Controls were sham-exposed to pure air for an identical period of time. Bronchoalveolar lavage was performed 24 hr after the beginning of exposure, and components of the lavage fluid considered to be indicators of inflammation were used to assess the severity of pulmonary inflammation. The results of this experiment showed that significantly enhanced sensitivity to ozone-induced pulmonary inflammation develops during pregnancy, is maintained during lactation, and disappears following lactation. Implicit in this pattern of differential sensitivity in rats is the possibility of a similar pattern of inflammatory response in analogous groups of humans as well as the potential for applicability to other oxidative pollutants. PMID- 1426720 TI - Maternity care: family centered or woman centered? PMID- 1426721 TI - The active phase of labor: a clarification. PMID- 1426722 TI - Pharmaceutical company-sponsored educational activities: who benefits? who pays? PMID- 1426723 TI - Supply and demand in residency positions. PMID- 1426724 TI - Family medicine in Lebanon: the 10th anniversary. AB - Developing a family practice residency program was a logical step in addressing the needs for primary care in Lebanon. The American University of Beirut initiated a family practice residency program in 1979. The curriculum was structured following the guidelines of the American Academy of Family Physicians. Since its establishment, the program has participated in the design, launching, and maintenance of the family practice residency in Bahrain. Future plans include establishing other programs in the region and increasing community participation. PMID- 1426725 TI - To be a mentor. PMID- 1426726 TI - The primary care research fellowship: an early assessment. AB - BACKGROUND: To address the continuing need for research-oriented faculty in primary care, the Bureau of Health Professions in 1988 funded 10 National Research Service Award (NRSA) Primary Care Fellowship Program grants. We report an early evaluation of these programs. METHOD: Descriptions of fellowship programs were obtained from grant proposals. Fellows with at least one year of training completed a mailed questionnaire that included both structured and open ended items. RESULTS: All programs emphasized research and gave mentorship explicit attention. Nine offered degree programs; six offered a third year of study. Twenty-seven of 32 eligible fellows returned the survey. They reported a median of three research projects during the fellowship. Sixty percent of fellows had extramural funding; 48% submitted manuscripts for publication; and 22% had work accepted for publication. In open-ended responses, fellows emphasized the importance of mentors' guidance on projects, accessibility, and emotional support; rarely did they mention help in establishing professional networks or in securing project funding. Fellows most appreciated the collegiality and protected atmosphere of fellowship programs, although they felt that both human and material resources were less than optimal. CONCLUSIONS: Fellowship environments are generally conducive to productivity, and fellows undertake relevant primary care research. Programs should devote more attention to mentoring, especially regarding networking and obtaining funding. Funding agencies should increase support for training-related expenses in lieu of research grants that subsidize NRSA training in other specialties. PMID- 1426727 TI - Female family doctors: their work and well-being. AB - BACKGROUND: The role of female physicians, which often involves combining medicine, marriage, and motherhood, may cause stress for some women. The purpose of this research was to identify correlates of depression, stress, and self esteem among a sample of female Canadian family physicians. METHODS: All female family physicians in London, Ontario, who met study eligibility criteria were asked to participate in a questionnaire study. Sixty-two physicians were surveyed and asked to complete four psychological survey instruments: the Cognition Checklist, the Coopersmith Self-Esteem Inventory, the People in Your Life Scale, and the Work Response Questionnaire. RESULTS: The response rate was 83.3%. Sixty five percent of subjects felt overloaded or overwhelmed at least once per week. These women, on average, worked more hours than subjects who reported not feeling overwhelmed (r = .48). Subjects had lower depression scores than did other populations tested with similar survey instruments. Subjects' self-esteem was similar to that found in other populations and was positively correlated with opportunities to acquire new skills (r = .34) and perceived lack of difficulty in developing lasting relationships (r = .41). CONCLUSIONS: Depression appears to be less common among female family physicians than among other populations, but nearly two thirds of female family physicians feel overloaded or overwhelmed by their multiple responsibilities, as often as once per week. PMID- 1426728 TI - Medical school financial support, faculty composition, and selection of family practice by medical students. AB - OBJECTIVE: This study examines the relationship between the choice of family practice by medical students in the 1986-1987 academic year and nine variables: ownership of school, weeks of required family medicine clinical training, age of school, and six variables related to medical school financial support and faculty composition. METHODS: In multivariate analysis, three variables were found to be significantly related to choice of family practice (R2 = .441): weeks of required family medicine clinical training, proportion of faculty in family practice, and ownership of the school. A cluster analysis was performed using nine variables. RESULTS: Along with the multivariate analysis, the resulting nine clusters demonstrate that additional variables need to be identified to explain the variance in percentage of students choosing family practice at different schools. PMID- 1426729 TI - Religious variables are infrequently reported in clinical research. AB - BACKGROUND: More than 200 published studies have found some relationship between an individual's religion and health, yet reference to religious variables rarely appears in published empirical studies. METHODS: We performed a manual search of all articles reporting on human subjects in the 1989 issues of seven major medical journals to record and analyze religious and other demographic variables. RESULTS: Only 12 of the 1,066 articles (1.1%) mentioned religion, and eight of these mentioned only denominational affiliation. CONCLUSION: Most clinical investigators do not report on the religious variables of their subjects and thus may be missing important correlations. PMID- 1426730 TI - Participation by sedentary elderly persons in an exercise promotion session. AB - BACKGROUND: Little is known regarding the dynamics of elderly persons' participation in health promotion programs. We studied factors influencing the participation of 337 sedentary elderly persons in an exercise promotion session. All study participants were members of a health maintenance organization. METHODS: Baseline data were obtained on 337 persons age 65 and older who exercised irregularly or not at all. These individuals were then offered a class emphasizing individualized exercise activities for elderly persons. Participation in the exercise program was used as the dependent variable, and the baseline data were analyzed to identify factors associated with participation. RESULTS: There was no difference between participants and nonparticipants for age and sex. Baseline physical activity, as measured by the Paffenbarger index and self-report of physical activity, also did not differentiate participants from nonparticipants, nor did frequency of self-reported medical conditions. Participants were more likely to be nonsmokers, but the two groups did not differ with respect to other preventive health practices. Participants were characterized by more social interactions, as reflected by attendance at at least two meetings per month. Participants also were more likely to report three or more close friends. Perceived quality of life and self-reported health status were not significantly different between the two groups. Participants rated their current health slightly worse than nonparticipants. In a logistic regression model controlling for age and sex, lower current health perceptions, greater number of friends, prior expressed intent to participate in an exercise program, being a nonsmoker, and having received an influenza vaccination in the past year were significantly associated with participation. CONCLUSIONS: Participation in this exercise program may have appealed to persons with higher levels of social interaction. In this population, age, sex, and the number and type of self reported medical conditions at baseline were not predictive of participation. PMID- 1426731 TI - Hospital charting of substance use. AB - BACKGROUND: Recent evidence suggests that physicians can help patients reduce or even discontinue cigarette smoking. Physicians may also be able to help patients decrease their use of alcohol or illegal drugs. A prerequisite for helping patients decrease substance use is for physicians to ask patients about their use of cigarettes, alcohol, and illicit drugs. METHODS: We performed a retrospective study of 212 medical records to measure physicians' documentation of patient use of alcohol, cigarettes, and illicit drugs in an inpatient setting. The study compared residents and attending physicians in family practice and internal medicine. RESULTS: Physicians charted cigarette use in 73% of medical records, alcohol use in 70%, and drug use in only 12.5%. Family physicians charted substance use more frequently than internal medicine physicians for alcohol and illicit drugs (P < .05 by Pearson's chi-square analysis) and for cigarettes (P = .07). In each specialty, residents charted substance use more often than attending physicians (P < .01). Attending family physicians (P < .05) charted substance use more often in male than in female patients. This was not found among internal medicine physicians. CONCLUSION: The results of the study suggest that the stage of medical career, medical specialty, and sex of the patient affect the frequency of charting substance abuse. PMID- 1426732 TI - Voices from family medicine: cooperation across disciplines. Interview by William B. Ventres, John J. Frey and Alfred O. Berg. AB - A variety of individuals lent their efforts to the establishment of family medicine as an academic discipline. Many had careers outside general or family practice, yet because of their interests and active involvement, they helped forge the way toward a rational and comprehensive education for family physicians in this country. In this transcript, edited from interviews conducted in 1992, four contributors from other disciplines discuss their perspectives on the history of family medicine. PMID- 1426733 TI - [Patterns of changes of the cellular component of the hemoimmune system in elevated pressure of the gaseous environment]. PMID- 1426734 TI - [Superslow oscillations of the 10-minute band potential and dynamics of immunobiochemical parameters of the cerebrospinal fluid in patients with optochiasmatic arachnoiditis and brain neoplasms in the postoperative period]. PMID- 1426735 TI - [Lung volume changes during cold air breathing in construction workers in northern regions of Western Siberia]. PMID- 1426736 TI - [Buffer systems in calcium homeostasis regulation in man]. PMID- 1426738 TI - [Determination of the degree of dispersion of an aerosol and the effect of the inhalation regimen on its distribution in the lungs]. PMID- 1426737 TI - [Normal and pathologic gastric secretion of bicarbonates in man]. PMID- 1426739 TI - [Functional interaction of the opioid-catecholamine system in children with glomerulonephritis]. PMID- 1426740 TI - [Constitutional types and testosterone concentration in men's saliva during exposure to local vibration]. PMID- 1426741 TI - [Equipment and software for the study of oxygen tension dynamics in the human brain]. PMID- 1426742 TI - [A method of computerized encephalogram correction for future analysis]. PMID- 1426743 TI - [Heart rate dynamics during night sleep in patients with epilepsy]. PMID- 1426744 TI - [Assessment of the resistance of the human body to combined thermal, physical and emotional load]. PMID- 1426745 TI - [Intracavitary pressure monitoring in upper regions of the digestive tract]. PMID- 1426746 TI - [Information processing during adaptation]. PMID- 1426747 TI - [Contrast temperature exposure as preliminary thermal adaptation of pilots to hot climate]. PMID- 1426748 TI - [Contractile properties of human triceps muscle of the calf in conditions simulating weightlessness]. PMID- 1426749 TI - [Effect of information about performance effectiveness on a human heart rhythmogram]. PMID- 1426751 TI - [Heart rate during a test of six breaths per minute]. PMID- 1426750 TI - [Functional state of the autonomic nervous system in women during adaptation to high altitudes and readaptation to low altitude conditions]. PMID- 1426752 TI - [Value of the study of hemodynamics of physical exercise for the detection of latent forms of cardiac insufficiency in patients in the early period of myocardial infarction]. PMID- 1426753 TI - [Assessment of the functional state of the cardiovascular system by signals of the aortal wall movement]. PMID- 1426754 TI - [Wave mechanism of systemic organization of sportsmen's movements]. PMID- 1426755 TI - [Motor reaction parameters during the development and control of persistent emotional disorders]. PMID- 1426756 TI - [Individual characteristics of behavior and autonomic tonus in young children attending daycare facilities]. PMID- 1426757 TI - [Cardiointervalography as a criterion for identifying the "risk phase" in the menstrual cycle of healthy women]. PMID- 1426758 TI - [Comprehensive approach to the study of athletes' immune status]. PMID- 1426760 TI - Can indirect cost funding be improved? AB - Like the tax laws many possible loopholes are in these proposed changes and therefore they have to be considered very carefully. If there is such a thing as a collective wisdom, it should be brought to bear on this problem. With strong and well-considered actions, which would be implemented in a controlled way, the mechanisms for funding research could be improved to encourage efficient use of funds. PMID- 1426759 TI - Common dollars and sense. PMID- 1426761 TI - Resolution of the indirect cost issue. PMID- 1426762 TI - Regulation of glucose transport in skeletal muscle. AB - The entry of glucose into muscle cells is achieved primarily via a carrier mediated system consisting of protein transport molecules. GLUT-1 transporter isoform is normally found in the sarcolemmal (SL) membrane and is thought to be involved in glucose transport under basal conditions. With insulin stimulation, glucose transport is accelerated by translocating GLUT-4 transporters from an intracellular pool out to the T-tubule and SL membranes. Activation of transporters to increase the turnover number may also be involved, but the evidence is far from conclusive. When insulin binds to its receptor, it autophosphorylates tyrosine and serine residues on the beta-subunit of the receptor. The tyrosine residues are thought to activate tyrosine kinases, which in turn phosphorylate/activate as yet unknown second messengers. Insulin receptor antibodies, however, have been reported to increase glucose transport without increasing kinase activity. Insulin resistance in skeletal muscle is a major characteristic of obesity and diabetes mellitus, especially NIDDM. A decrease in the number of insulin receptors and the ability of insulin to activate receptor tyrosine kinase has been documented in muscle from NIDDM patients. Most studies report no change in the intracellular pool of GLUT-4 transporters available for translocation to the SL. Both the quality and quantity of food consumed can regulate insulin sensitivity. A high-fat, refined sugar diet, similar to the typical U.S. diet, causes insulin resistance when compared with a low-fat, complex-carbohydrate diet. On the other hand, exercise increases insulin sensitivity. After an acute bout of exercise, glucose transport in muscle increases to the same level as with maximum insulin stimulation. Although the number of GLUT-4 transporters in the sarcolemma increases with exercise, neither insulin or its receptor is involved. After an initial acute phase, which may involve calcium as the activator, a secondary phase of increased insulin sensitivity can last for up to a day after exercise. The mechanism responsible for the increased insulin sensitivity with exercise is unknown. Regular exercise training also increases insulin sensitivity, which can be documented several days after the final bout of exercise, and again the mechanism is unknown. An increase in the muscle content of GLUT-4 transporters with training has recently been reported. Even though significant progress has been made in the past few years in understanding glucose transport in skeletal muscle, the mechanisms involved in regulating transport are far from being understood. PMID- 1426763 TI - Regulation of transferrin gene expression. AB - Transferrin (Tf) is the iron-transport protein of vertebrate serum. It is essentially synthesized in the liver, but lower amounts are also produced in other organs, such as testis and brain. A number of studies have been done to characterize the transcriptional elements implicated in the regulation of Tf gene expression in different organs. The results of these studies support the hypothesis that the Tf gene makes use of different combinations of nuclear proteins in different subsets of cells to achieve tissue-specific expression. It is interesting to point out that this occurs in tissues arising from different embryological origin. PMID- 1426764 TI - SAPA/trans-sialidase and cruzipain: two antigens from Trypanosoma cruzi contain immunodominant but enzymatically inactive domains. AB - Trypanosoma cruzi, the parasitic protozoan that causes the American trypanosomiasis, or Chagas disease, contains a number of antigenic molecules, some of which have tandems of amino acid repeats. One of these molecules, SAPA (shed acute phase antigen), contains a so-far unique trans-sialidase activity that is essential for penetration of the parasite into mammalian cells. The enzyme consists of two different domains, one presumably enzymatic, which contains four copies of an amino acid motif conserved in bacterial neuraminidases, and the other highly antigenic, consisting of the repeats. Another enzyme that seems to be involved in the host-parasite relationship, the cysteine proteinase cruzipain, is also made up in its mature form of a catalytic domain with high homology to cathepsin L and a COOH-terminal domain that is highly antigenic in vivo. These bifunctional molecules may have arisen by incorporation of a highly antigenic domain to an essential enzyme in order to attract the immune response, thus protecting the enzyme activity. PMID- 1426765 TI - Tyrphostins: tyrosine kinase blockers as novel antiproliferative agents and dissectors of signal transduction. AB - Protein tyrosine kinases (PTKs) are members of a growing family of oncoproteins and protooncoproteins that play a pivotal role in normal and abnormal proliferative processes. This hallmark identifies these unique proteins as potential targets for antiproliferative therapy. This review discusses the current status of PTK inhibitors, with special emphasis on tyrphostins as antiproliferative agents and as potential drugs for cancers, leukemias, psoriasis, and restenosis as well as other proliferative conditions. The development of tyrphostins as selective signal blockers can be viewed as a first step toward the development of "smart" cocktails as antiproliferative agents. Each of these custom-made cocktails will be aimed at proliferative conditions whose transduction pathways can be characterized by molecular tools. The review also discusses the use of PTK blockers as tools to study signal transduction processes in which protein tyrosine kinases are implicated. PMID- 1426766 TI - Thrombospondins: structure and regulation of expression. AB - Thrombospondin (TSP) is a large, trimeric, modular glycoprotein that is a major constituent of platelet alpha granules. TSP is also secreted by a wide variety of epithelial and mesenchymal cells in patterns that reflect developmental changes in the embryo and response to injury in the adult. In addition to its role in blood coagulation, TSP has been reported to serve both adhesive and anti-adhesive functions, to foster neurite outgrowth, stimulate and inhibit cell growth and migration, and inhibit angiogenesis. Although this diversity in apparent function can be attributed, in part, to the ability of a single TSP to interact with several different cell-surface receptors, it is now known that the TSPs are encoded by at least three homologous genes in both human and mouse. TSP1, the commonly recognized protein isolated from platelets, is similar to TSP2 in structure. Both proteins contain NH2-terminal, COOH-terminal, and procollagen homology domains, and type I (TSP or properdin), type II (EGF-like), and type III (Ca(2+)-binding) repeats. However, the two TSPs differ in amino acid sequence and in the regulation of their expression. TSP1 is rapidly induced by serum and growth factors. An SRE and a binding site for NF-Y have been shown to mediate the serum response of the human TSP1 gene. On the other hand, TSP2 is far less responsive to serum than TSP1 and lacks the promoter elements that mediate the serum responsiveness of TSP1. TSP3 resembles TSP1 and TSP2 in its COOH-terminal domain and type III repeats, but contains four rather than three type II repeats and lacks type I repeats and a procollagen homology. The NH2-terminal domain of TSP3 also differs from that of either TSP1 or TSP2. All three TSPs demonstrate characteristic patterns of expression in the developing and adult mouse. It is therefore likely that each protein subserves a discrete function. In the future it will be necessary to distinguish among the three TSPs in addressing the function of these proteins. PMID- 1426767 TI - Transcription by RNA polymerase II: initiator-directed formation of transcription competent complexes. AB - Studies of transcription by RNA polymerase II have revealed two promoter elements, the TATA motif and the initiator (Inr), capable of directing specific transcription initiation. Although binding to the TATA motif by one of the components of the transcription machinery has been shown to be the initial recognition step in transcription complex formation, many promoters that lack a traditional TATA motif have recently been described. In such TATA-less promoters, the Inr element is critical in positioning RNA polymerase II. Various Inr elements have been described and classified according to sequence homology. These Inr elements are recognized specifically by Inr-binding proteins. Interaction between these Inr-binding proteins and components of the basal transcription machinery provides a means through which a transcription competent complex can be formed. PMID- 1426768 TI - Glucocorticoid regulation of phenylethanolamine N-methyltransferase in vivo. AB - In vivo, supraphysiological doses of glucocorticoids are required to restore adrenal medullary phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28) activity after hypophysectomy. However, in vitro, phenylethanolamine N methyltransferase gene expression appears normally glucocorticoid-responsive. To explore this paradox, rats were given dexamethasone or the type II-specific glucocorticoid RU28362 (1-1000 micrograms/day), and adrenal phenylethanolamine N methyltransferase activity and mRNA levels were determined. At low doses (1-30 micrograms/day), neither steroid altered mRNA whereas at higher doses (100-1000 micrograms/day), mRNA rose 10- to 20-fold, with dexamethasone approximately 3 times as potent as RU28362. In contrast, enzyme activity fell with low doses of either steroid, consistent with suppression of ACTH and endogenous steroidogenesis. At higher doses of RU28362, enzyme activity remained low and unchanged despite increased mRNA expression, whereas higher doses of dexamethasone progressively restored the enzyme to normal. These findings suggest 1) that glucocorticoid regulation of phenylethanolamine N-methyltransferase activity occurs largely independent of gene expression; 2) that glucocorticoid effects on enzyme activity are primarily indirect, probably through cosubstrate regulation and/or enzyme stabilization; and 3) that these effects are not mediated via a classical (type II) glucocorticoid receptor mechanism, given the high doses of dexamethasone and corticosterone required and the inability of RU28362 to mimic the effects of these less selective steroids. PMID- 1426769 TI - Vitamin C and serendipity, fifty years ago. PMID- 1426770 TI - [Efficacy of intravenous and per os propafenone in the ambulatory treatment of recent-onset atrial fibrillation]. AB - Propafenone efficacy in conversion of atrial fibrillation to sinus rhythm has been well documented. In this study we considered propafenone efficacy according to a graduated protocol of administration. Forty-two patients with recent-onset atrial fibrillation, without left ventricular failure, ischemic symptoms and in absence of antiarrhythmical treatment, were treated according to the following protocol: propafenone 1 mg/kg i.v. (5 min) followed, in the non-responder patient group, by a second dose, 0.5 mg/kg i.v. (15 min). Patients with persistent atrial fibrillation received 900 mg/daily of propafenone per os, at home for two days. Thereafter, patients still not restored to sinus rhythm were considered non responders. Patients who were converted to sinus rhythm received 450 mg daily of the drug (oral administration), at home, as antiarrhythmical prophylaxis, for three months. Thirty-nine patients were converted to sinus rhythm (92.8%), 24 of them after intravenous propafenone (57.2%), and the other 15 (35.6%) after oral administration of the drug. The average heart rate in patients not converted to sinus rhythm with intravenous propafenone was significantly reduced after drug administration, compared to basal values (from 136.4 +/- 18.1 to 107.1 +/- 17.6, p < 0.01), allowing home treatment. No major cardiac effects were observed after infusion, nor after oral administration of propafenone. During a three-month follow-up we observed 3 cases of relapsed atrial fibrillation and 2 discontinued treatments due to minor gastroenteric side effects. In conclusion, propafenone therapy in ambulatory regimen is safe and effective in patients with recent-onset atrial fibrillation. In many patients refractory to IV treatment, further therapeutic success may be achieved following oral propafenone administration. PMID- 1426771 TI - [Ventricular late potentials in hypertrophic cardiomyopathy: personal contribution and analysis of the literature]. AB - BACKGROUND: Patients with hypertrophic cardiomyopathy are at increased risk of sudden death. Recently it has been investigated whether late potentials can be useful markers of that risk in such patients, with discordant results. The aim of our study was to detect a correlation, if any, between late potentials, ventricular tachycardia and the hypertrophy extension. METHODS: Twenty-five patients were enrolled, 19 males and 6 females, mean age 40.40 +/- 15.02 years. Each underwent 24h Holter monitoring, averaged ECG, M-Mode and 2-D Echo. The hypertrophy was considered extensive (septum and free wall) or non extensive (septum and/or apex). RESULTS: Late potentials of a mean duration of 37 +/- 14.83 ms were recorded in 5/7 patients with documented ventricular tachycardia vs in none of the non tachycardia group. Sensibility was 100%, specificity 71% and predictive value 100%. Late potentials were present in 8.3% of patients with non extensive and in 30.8% of patients with extensive hypertrophy (p = NS). CONCLUSIONS: From our data it seems that extensive hypertrophy is present in about half of patients with hypertrophic cardiomyopathy, and this roughly correlates with a more frequent ventricular tachycardia and with late potentials. Furthermore, late potentials are strictly related to the incidence of ventricular tachycardia in this disease, just as in ischemic heart disease or in idiopathic dilated cardiomyopathy. The small number of our cases may not be sufficient to reach a significant statistical correlation between late potentials and hypertrophy, but we believe that the trend is very promising. PMID- 1426772 TI - [Drop in cardiovascular and coronary mortality in Lombardia, 1969-1987. Evaluation of reliability of the estimates and possible explaining hypothesis]. AB - The results of the present analysis indicate, from 1969 to 1987, a sharp and stable decline in cardiovascular (CVD) mortality in Italians aged 35-74 years (37.6% in males 53.6% in females). These trends were responsible for consistent reductions of total mortality (27.5% and 38% in the two gender groups, respectively), and for the increase of life expectancy. The decrease involved the two major components of CVD mortality, i.e. coronary heart disease (CHD) (23% in males and 44% in females) and cerebrovascular diseases (Stroke) (42.6% in the former and 51% in latter gender group). All these mortality decrements have been higher in the Lombardia Region. Comparing age-adjusted mortality rates in 1968 and 1987, it was possible to estimate that 23,040 deaths were saved in one year among the residents of this northern part of Italy, and the decrease of CHD mortality was responsible for about 30% of the total national decrement of CHD deaths, within comparable age strata. This is attributable both to the higher rates registered at the beginning of the studied period, and to the sharper decline observed. The social impact, in terms of reduction of deaths, was prominent for males. Among the northern male population, the amount of prevented deaths due to CHD and Stroke was equivalent (2072 vs 2172). Data from a MONICA Collaborating Center, located in the region--Area Brianza--, allow us to estimate, for coronary diagnoses reported on death certificates in the 1980s, acceptable levels of accuracy (Cohen's Kappa of .35, with 99% CI .27-.43) and sensitivity (87%). In comparison with earlier estimates carried out in the late 1970s, it is possible to hypothesize an increase of sensitivity over time for certified myocardial infarction diagnoses, which could have contributed to the underestimation of the observed decrements. In dealing with estimates of the reasons for these declines, only suggestions could be addressed because results of specific and comprehensive studies are not presently available. By comparing MONICA data with the results obtained in earlier surveys, it is possible to estimate that about 20 to 30% of the CHD decline, which occurred in the Region, might be attributed to the decrease of in-hospital coronary case-fatality. Moreover, major coronary risk factors (total cholesterol, blood pressure and cigarette smoking) show parallel positive changes, but their contribution in predicting the CHD downfall is difficult to evaluate on the basis of existing data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1426773 TI - [Heart-brain interactions: status of knowledge and perspectives of study]. PMID- 1426774 TI - [Left ventricular aneurysmectomy: technical evolution and results]. AB - A critical review of surgical techniques for left ventricular aneurysm treatment, with reference to literature data and author's personal experience, is reported. Aneurysm plicatio, performed in 35 patients, was always associated to coronary artery bypass graft and carried out mainly in small aneurysms of the posterior wall. In the last years this technique has been used very rarely, due to papillary muscle damage risk. Aneurysmectomy by usual technique only partially eliminates the a-dyskinetic area and moreover determines a severe ventricular deformation due to the linear suture. At Verona hospital it was carried out in 175 patients, with an 8% operative mortality and a survival rate of 82% at 3 years and of 80% at 5 years. Aneurysmectomy with converging walls left ventricular reconstruction, as proposed by Jatene and modified by the author, allows complete aneurysm removal and assures a ventricular reconstruction closer to normal morphology. In the Verona experience with this technique, referring to 51 patients operated up to 1989, operative mortality was 3.9% with a 89.9% survival rate at 3 years. These improved clinical results are associated with the improvement of left ventricular function indexes: average ejection fraction from 28.2% preoperatively to 42% postoperatively; average end diastolic left ventricular pressure from 23.6 mmHg to 18 mmHg. PMID- 1426775 TI - [Emergency surgery of acute coronary insufficiency]. AB - In our centre, during the last five years, emergency operations (within 6 hours) and urgent operations (within 72 hours) have represented 1/4 of all coronary surgery. 295 patients (pts) have been operated on since 1972: of these, 279 with simple revascularization, 5 with combined major surgery, and 11 as a consequence of mechanical complications of acute myocardial infarction. These last were all in cardiogenic shock: the overall 30-day mortality rate was 5.4% (3.6% in those pts with simple revascularization, 20% in those with combined major surgery, and 45.4% in pts with cardiogenic shock). In the subgroup with simple revascularization, the incidence of non fatal perioperative acute myocardial infarction (AMI) was 4.7% in 253 pts with unstable angina, 52.2% in 23 pts with abrupt closure during coronary angioplasty, and obviously 100% in 3 pts surgically treated during evolving AMI. We were able to identify in the univariate analysis as the only 30-day risk mortality factors: 1) a reduced ejection fraction (< 30%) and 2) the combination with endarterectomy. Other factors (female sex, age > 70, severity of angina, diffuse coronary artery disease and more than 3 by pass grafts) have shown a tendency to increase the mortality rate without statistical significance. No deaths occurred in pts revascularized in emergency situations due to coronary angioplasty complications. In recent years emergency and urgent coronary surgical operations have been increasing, with an increase in pts with higher risk factors. In pts with simple revascularization, 30-day mortality and incidence of myocardial infarction are similar to those of elective surgery. In pts with abrupt closure as a consequence of coronary angioplasty the mortality rate seems very low, while the incidence of infarction remains extremely high. These observations have allowed the development of an integrated protocol of intervention in acute unstable coronary syndromes. PMID- 1426777 TI - [Surgical treatment of diffuse coronary disease]. AB - Considering the morphological aspects of diffuse coronary disease one must argue that, in their presence, myocardial revascularization can be performed only by coronary endarterectomy (EA), together with conventional bypass grafting. A variety of EA techniques ("blind" and "open" EA) are analyzed. Indications, long and short-term results (operative risks, symptomatic improvement, grafts patency) of each procedure are evaluated on the basis of the current experiences. We conclude that EA is a valuable complement to coronary artery bypass grafting which allows: a) a larger number of conventionally inoperable patients to benefit from the surgical treatment; b) more complete revascularization in patients with diffuse coronary disease. PMID- 1426776 TI - [Surgical indications and results of myocardial revascularization in complications of PTCA]. AB - Acute coronary occlusion during PTCA represents a significant procedural complication occurring in approximately 4-5% of cases, most frequently because of coronary dissection, spasm, or thrombosis. In these cases the first step in the management of acute ischemia is 1) a brief evaluation of its hemodynamic consequences and 2) the assessment and treatment of its cause. Spasm and intracoronary thrombus formation are usually readily identifiable and treatable using intracoronary nitroglycerin and thrombolytic therapy. In our catheterization laboratory the current approach to occlusive coronary dissection is represented by the use of autoperfusion dilatation catheters and by stent application. The atherectomy devices and the laser "welding" of the dissected intimal segment represent other alternatives that are still under clinical evaluation in this particular setting. If coronary occlusion is refractory to these efforts and coronary blood flow is not reestablished rapidly, emergency coronary bypass surgery is required to salvage jeopardized myocardium. In this case myocardial ischemia may be lessened by the insertion of an intra-aortic balloon pump. In our experience, the incidence of death (4%) and myocardial infarction (37%) for emergency CABG after a failed angioplasty, is similar to that reported by other Authors. The duration of myocardial ischemia and the presence of cardiogenic shock before operation are the most important determinants of major complications such as death and acute myocardial infarction. PMID- 1426778 TI - [Repeat myocardial revascularization]. AB - Eighty-two consecutive patients undergoing reoperation for coronary revascularization from January 1980 to November 1990 were reviewed to determine early and late results and predictors of survival. Seventy patients were male and 12 female; age ranged from 36 to 75 years (mean 56.4 +/- 8.1). All were symptomatic for angina. The mean interval between first and second operation was 62.8 +/- 47.8 months (range 1 to 220 months). Angiographic indications for reoperation were: graft failure (34.1%), progression of atherosclerosis in the native coronary circulation (6.1%) and combination of the two (59.8%). Mean ejection fraction was 45.9 +/- 10.2 (range 11 to 67). Surgical indication was elective in 79.3%, urgent in 14.6% and emergent in 6.1%; 199 grafts were performed (2.4 +/- 1 grafts/patient). Hospital mortality was 6.1% (5 cases). Late mortality was 5.2% (4 cases). Actuarial survival rate (including hospital mortality) was 87.9% at 3, 5 and 10 years. Multivariate analysis identified left main stenosis (p = 0.00001), family history of coronary disease (p = 0.003), urgent/emergency operation (p = 0.015) as predictors of increased in-hospital mortality; postoperative myocardial infarction (p = 0.002) and preoperative heart failure (p = 0.01) as predictors of increased late mortality. Follow-up of in hospital survivors (mean interval 42.7 +/- 25.8 months, range 3 to 120 months) documented 27 cardiac major events (other than death) in 24 patients (32.9%). Actuarial rates of freedom from major cardiac events were 70%, 52.9% and 48.1% at 3, 5 and 10 years respectively. Multivariate analysis identified preoperative ejection fraction (p = 0.01) as predictor of recurrence of angina and preoperative heart failure (p = 0.02) as predictor of occurrence of cardiac major events. PMID- 1426779 TI - [Surgery of refractory ischemic arrhythmia]. AB - Since June 1980, 138 patients have undergone surgical treatment for refractory ventricular tachycardia due to ischemic heart disease. Electrically guided surgical ablation (EGSA) of the focus was performed in 117 patients, while 14 patients underwent application of automatic implantable cardioverter defibrillator (AICD), and 8 patients underwent heart transplantation. During the whole period considered, among the EGSA patients an operative mortality of 13 patients was observed (11.4%), with a late mortality of another 14 patients (13.4%). Two early and six late recurrences were described, and 4 cases of sudden or unexplained death, with 2 cases clearly due to an arrhythmic event. Multivariate analysis showed preoperative ejection fraction lower than 25% as a powerful predictor of early mortality (32% vs 0%). Actuarial survival rate of patients with LVEF lower than 25% was 67 +/- 12% vs 95 +/- 2% at one year and 37 +/- 25% vs 94 +/- 8% at 8 years. A high operative mortality was then observed in patients who underwent aneurysmectomy alone or visually guided procedures as compared to electrically guided procedures (75% or 3 deaths out of 4 patients vs 8.5% or 10 out of 113 patients, respectively). Patients who received an AICD with or without associated procedures showed 1 case of in-hospital mortality and no late mortality; in 6 patients at least one shock was delivered; in two patients the AICD was implanted during an EGSA procedure, due to multiple or difficult origins of the arrhythmias. Of patients who underwent heart transplantation one case of later mortality was observed due to malignancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426780 TI - [Navigating between Kos and Knidos]. PMID- 1426781 TI - [The authors of multicenter studies]. PMID- 1426782 TI - [Ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension]. AB - High resolution ultrasonography allows the accurate and reproducible measurement of thickness and lumen diameter of carotid arteries. We investigated Common carotid (CCA) and bifurcation intima-media thickness in 40 hypertensive patients, 20 without left ventricular hypertrophy (LVH) (age 42 +/- 10 years) and 20 with LVH (age 44 +/- 12 years), all free from other important cardiovascular risk factors. Both carotid axes were scanned from different views (anterior, lateral, posterior) on traversal and longitudinal section, using a high resolution steerable (HRS) 5.0 MHz linear array. Carotid diameter and thickness from longitudinal section were measured. CCA parameters were taken 20 mm caudally to flow divider. Using the B-mode as a guide we assessed LVH presence with M-mode technique when left ventricular mass index (LVMI) > or = 135 g/m2 for men and > or = 110 g/m2 for women. In hypertensive patients with LVH, left ventricular mass was significantly higher than in those without LVH (156 +/- 38 vs 98 +/- 10 g/m2, p < 0.01). Even blood pressure was significantly higher in hypertrophic group (172 +/- 21/108 +/- 9 vs 158 +/- 11/99 +/- 12 mmHg, p < 0.01), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness scanned in both CCA and bifurcation resulted significantly higher in hypertensives with LVH (CCA: 0.85 +/- 0.02 mm vs 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 mm vs 0.70 +/- 0.03 mm, p < 0.01). We also noticed a statistically significant correlation between carotid wall thickness and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426783 TI - [Complications and sequelae of cardiac electrostimulation in children. Our experience with 47 children]. AB - Permanent cardiac pacing is now easily feasible in children and even in small infants, but the long-term results of this procedure are not well known. We analyzed our experience to determine the morbidity of pacing in children. Over the past 10 years, 47 pediatric patients (pts) required pacemaker implantation in our institution. The mean age was 8.3 +/- 4 years (1 day-17 years) and mean body weight was 23 +/- 14 Kg (2.2-60 Kg). 25 pts had heart disease. 40 children had an A-V block (congenital in 22 cases, post-operative in 17 pts, and secondary to a systemic disease in 1 case); 7 pts had a sick sinus syndrome, primitive in 4 and postoperative in 3 cases. The first pacemaker implantation was epicardial in 17 and transvenous in 30 pts. The pacing was single-chamber in 45 pts (VVI 32, VVIr 7, AAI 5, AAIr 1) and dual-chamber in 2 pts (DDD 1, VDD 1). Two newborns, both with a congenital A-V block and severe heart failure, died in the first hours after epicardial pacing. Two other children, both with congenital heart disease, died during follow-up, but the death was not pacemaker-related. Finally, two children were lost to follow-up. The mean follow-up of the 41 remaining pts was 5.2 +/- 3.5 years (4 months-10 years). Twelve children (29%) required 19 implant revisions and the causes were: lead fracture (26%), rising stimulation threshold (26%), growth problems (21%), erosion and/or pocket infection (21%). Revisions were more common in epicardial (52%) than in endocardial (22%) implantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426784 TI - [Determination of prevalence and control level of hypertension in the community: Hypertension Management Audit Project--Vicenza]. AB - As a part of the "Hypertension Management Audit Project" a random sample of 4070 subjects was drawn from the population aged 35-64 living in the city of Vicenza, in order to assess the prevalence and the level of control of hypertension in the community. 2854 (70.1%) were screened in the first step of the survey. Two blood pressure (BP) reading, height and weight measurements were performed and a short questionnaire filled in. Systolic BP (SBP) and diastolic BP (DBP) were (mean and 95% confidence interval) 143.7 (142.6-144.7) and 88.3 (87.7-88.8) mmHg in males; 137.8 (136.8-138.8) and 84.9 (84.5-85.5) mmHg in females, respectively. The BP value corresponding to the 95 degrees percentile of the cumulative distribution of BP was 180 mmHg for SBP and 105 mmHg for DBP in males; 173 mmHg for SBP and 100 mmHg for DBP in females. Systo-diastolic hypertension was present in 12.3% of the screened population; isolated diastolic hypertension in 9.1%; isolated systolic hypertension in 5.3%; borderline hypertension in 31.6%; severe hypertension (DBP > or = 115 mmHg) was present in 1.9% of females and in 2.2% of males. Prevalence in males was significantly higher with respect to females in all three categories of defined hypertension, but not in borderline hypertension. The second step of the survey involved 849 subjects (29.7% of the screened population) who completed two re-examinations because at the screening they had: 1) history of high BP; 2) BP > or = 160/95 mmHg; 3) ongoing antihypertensive treatment. At the end of the survey, 772 of these subjects (91%) were confirmed as hypertensives (mean BP of six readings > or = 140/90 mmHg and/or taking antihypertensive drugs). Patients aware of their high BP were 78.8%; aware and treated 51.0%; treated and controlled (BP < 140/90 mmHg) 19.1%. All indices of control were significantly higher in female with respect to male patients. Treated patients were significantly older than untreated patients; treated females had significantly lower BP than treated males, whereas no difference was detected between untreated patients; patients unaware of high BP had the highest BP values if compared to treated and untreated patients. This survey reveals a high prevalence of hypertension in the adult population of the city of Vicenza; quality of control shows a moderate improvement if compared to previous studies carried out in our country. PMID- 1426785 TI - [Anatomo-functional study of non-rheumatic mitral insufficiency with transesophageal echocardiography]. AB - Reconstruction surgery of the mitral valve has become an alternative to mitral replacement in patients with pure mitral regurgitation. Preoperative assessment of the anatomic and functional aspects of the valvular lesion is of the utmost importance in conservative surgery. Transesophageal echocardiography is a new approach to investigating the mitral valve, and our study was undertaken with the purpose of determining its importance in the exploration of mitral regurgitation of non-rheumatic origin. Subjects included were twenty patients with pure and isolated mitral regurgitation (MR): 14 males and 6 females with an average age of 47 +/- 13 years. All the patients underwent a first transesophageal 2D and color Doppler echocardiographic examination, and 5 of them underwent a second one during cardiovascular surgery. Mitral anulus diameter, mitral valve cordae tendinae status, valvular leaflet length and coaptation were examined and color Doppler regurgitation jet area was measured. Mitral anulus diameter was 40.2 +/- 8.06 mm (diastolic) and 41.9 +/- 8.53 mm (systolic) and was above the values considered to be normal. Anterior leaflet length was 30.8 +/- 3.12 mm and posterior leaflet length was 22.9 +/- 4.74 mm; regurgitation jet area was between 1.2 cm2 and 13.52 cm2 with an average of 5.44 cm2. In the group with MR of mixomatous origin, systolic anulus diameter showed a linear correlation with regurgitation jet area (r = 0.79). In the 6 patients who underwent cardiac catheterization, angiographic semiquantitative evaluation of the MR confirmed that based on color Doppler jet area. In all twenty patients transesophageal echocardiography enabled us to identify the mechanism responsible for mitral insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426787 TI - [Thrombolytic therapy in acute myocardial infarction. Clinical studies on mortality]. PMID- 1426786 TI - [Regression of left ventricular hypertrophy in obese hypertensive patients treated with diet and pharmacologic therapy]. AB - Thirty-five obese (Body Mass Index: BMI > 30) hypertensive (diastolic blood pressure > 100 mmHg) patients were studied for 6 months. 18 patients (10 males, mean age 52 +/- 6 years) were treated with captopril 50 mg b.i.d. (Group 1); 17 patients, matched by age, sex and BMI were treated with captopril 50 mg b.i.d. and hypocaloric diet (Group 2). During follow-up a good control of blood pressure levels (< 150/90 mmHg) and a significant reduction in body weight (> 10%) were achieved in all patients of Group 2. Left heart anatomy was accessed by 2D guided M-mode echocardiogram before starting treatment and after 6 months. In Group 1 Interventricular Septal Thickness (ST), Posterior Wall Thickness (PWT) and Left Ventricular Mass (LVM) decreased significantly (p < 0.01). In Group 2 not only ST, PWT and LVM decreased significantly (p < 0.01 for ST and PWT, p < 0.001 for LVM), but also left atrial dimension (p < 0.05) and left ventricular diastolic dimension (p < 0.01). The percent reduction in AD, LVDD and LVM was significantly higher (p < 0.01) in Group 2. In obese hypertensives relevant weight loss can improve the effect of captopril treatment on left ventricular hypertrophy; the decrease of AD and LVDD is probably secondary to a reduction of the volume overload present in obese patients. PMID- 1426788 TI - Methodology of baroreflex testing. AB - Recent clinical data have generated fresh interest in the assessment of baroreflex sensitivity, largely because of the relationship between this parameter and prognosis after a myocardial infarction. The present article reviews and discusses some of the methodologies currently used for the determination of baroreflex sensitivity. The Neck Chamber involves stimulation of the carotid baroreceptors by either augmenting or decreasing pressure at the level of the neck. The main advantage of this technique is to allow the simultaneous measurement of changes in heart rate and in the peripheral resistances. Another advantage is represented by the fact that no drugs are necessary for this type of study. On the other hand, this procedure modifies autonomic influences in several receptors areas while the stimulus is acting only at the carotid level; as a result of the baroreceptor activation or deactivation, this will produce complex and not uniform afferent information from receptors that are exposed to mechanical stimuli of opposite direction. In addition, it is difficult to quantify the pressure transmitted to the baroreceptors located in the carotid wall. The use of vasoactive substances, usually phenylephrine or nitroglycerin, produces a brisk change in pressure which is then linearly correlated with the attendant changes in the R-R interval to obtain a "baroreflex slope". The first concern with vasoactive drugs is that they act also on smooth muscle in the carotid sinus wall and might thereby interfere with the mechanical effects on the baroreceptors. The second is that peripheral resistance cannot be calculated at the same time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426789 TI - Power spectral analysis of RR variability. AB - The analysis of beat-to-beat spontaneous oscillations of heart rate variability is a recent and noninvasive approach capable of providing important information on neural mechanisms controlling cardiovascular function. In particular, with spectral analysis of RR variability, two major components can be detected at low (LF, approximately 0.1 Hz) and high (HF, approximately 0.25 Hz) frequency. They have been demonstrated to be appropriate indices of, respectively, sympathetic and parasympathetic modulations of heart period. In control subjects, at rest, LF is slightly predominant over HF. In post myocardial infarction patients there is a predominant LF and a diminished HF that suggests an alteration of sympatho vagal balance with a predominance of sympathetic tone. This approach, by providing indices of sympathetic and vagal neural regulatory outflows, appears adequate to evaluate several pathophysiological conditions such as ischemic heart disease, hypertension or congestive heart failure, which are characterized by important alterations of neural regulatory mechanisms. PMID- 1426790 TI - The neck chamber technique. AB - Since the first description of the neck chamber technique for stimulating carotid baroreceptors by Ernsting and Parry in 1957, a number of different neck collars have been realized, among which the simplified version devised by Eckberg and coworkers in 1975 and the neck chamber described by Ludbrook and coworkers in our Institute in 1977. At variance with Eckberg's type, the "Milan neck chamber" completely surrounds the neck and allows the application of both positive and negative pressures to the neck by means of a system of double rubber valves that prevents air leakage from the chamber. The main advantage of this technique, as compared to infusion of vasoactive drugs, is the possibility it offers to study baroreflex control not only of heart rate, but also of peripheral resistance and blood pressure through neck chamber induced changes in carotid transmural pressure. In recent years a systematic evaluation of the neck chamber technique has allowed to clarify the following issues: 1) application of positive pressure to the neck, although increasing internal jugular venous pressure and thereby reducing the pressure gradient from the arterial versus the venous side of head circulation, does not reduce cerebral blood flow; 2) changes in pressure within the neck chamber do not seem to reduce blood flow to the carotid bodies, at least to a degree which might lead to chemoreceptor stimulation; 3) there is a linear relation between changes in neck chamber pressure and changes in tissue pressure adjacent to the carotid sinus. The transmission of pressure to pericarotid tissues is complex, however.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426791 TI - Clinical assessment of respiratory sinus arrhythmia by computerized analysis of RR interval and respiration. AB - Heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) are often considered as interchangeable terms. However, the application of power spectral analysis to describe spontaneous fluctuations in heart period has clearly shown that RSA is only a part of HRV, and that in specific situations their respective patterns may diverge. In order to quantify the RSA we have used a mathematical method based on combined spectral analysis of respiration and RR interval (cross correlation function), and evaluated its performance in terms of reproducibility, sensitivity to parasympathetic withdrawal and in clinical evaluation of autonomic function. Compared to other indices of HRV the cross-correlation between RR interval and respiration showed a greater sensitivity to parasympathetic withdrawal, better reproducibility and a high sensitivity in detecting autonomic dysfunction in diabetic patients. These findings suggest that specific indices of RSA, such as the cross-correlation, can be a valid tool for the diagnostic approach to cardiac autonomic dysfunction. PMID- 1426792 TI - [Lack of tolerance after administration of delayed-action isosorbide-5 mononitrate for 3 days in patients with exercise-induced silent ischemia: control with placebo]. AB - In order to assess the development of tolerance we analyzed in a placebo controlled study the effect of monotherapy with isosorbide-5-mononitrate (IS-5 MN) 60 mg in a controlled release formulation (Durules) once-a-day. The IS-5-MN was evaluated after the first dose and after once-a-day therapy for three days in 11 ambulatory patients (10 males, 1 female, aged 54 +/- 9 years) with stable exercise-induced silent myocardial ischaemia and significant coronary stenoses. The drug was given at 8 o'clock in the morning, and a bicycle ergometer exercise test was performed after 4 hours. The ST segment depression was evaluated by a computer-assisted system. Standing blood pressure decreased during all three periods of active treatment with IS-5-MN, (in comparison with placebo p < 0.001 and p < 0.01, p < 0.01 respectively). Heart rate did not change significantly. Compared with placebo baseline values, ischaemic threshold increased during the first day of treatment (188 sec, p < 0.0001 at 4 hours), and to a lesser extent both in second (103 sec, p < 0.003) and third day (116 sec, p < 0.003). The total exercise time increased during all three days of active therapy but significantly so only during the first day. The exercise stress test performed in the 5th day during placebo demonstrated a high reproducibility of ischaemic-threshold (235 vs 241 sec, p: ns), implying that the improvement during the active treatment with IS-5-MN was not due to a "training effect". Headache in 2 patients was the only significant side-effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426793 TI - [Perfusion catheter and cardio-pulmonary support standby: organizational strategy for high risk PTCA. Description of a case treated successfully]. AB - The organizational strategy used in a high risk Coronary Angioplasty procedure is discussed. The attempted vessel was a severely stenosed Right Coronary Artery in a patient who had undergone triple graft, with residual obstruction of Left Main Artery and only one patent venous graft on a marginal branch of the Circumflex artery. The procedure was performed using a Stack type autoperfusion balloon angioplasty catheter, with a Cardiopulmonary Support System held in standby. PMID- 1426794 TI - [Sepsis and endocarditis: two rare complications following pacemaker implantation. Description of a case and review of the literature]. AB - A case of Staphylococcus aureus tricuspid valve endocarditis in a patient with permanent transvenous VVI pacemaker and recurrent febrile episodes is described. Medical treatment was not effective, and only with surgical removal of the lead was the infection successfully treated. PMID- 1426795 TI - [Infective endocarditis of the right heart in patients with pacemaker]. PMID- 1426796 TI - [Salt and hypertension in the 90's: a settled controversy?]. PMID- 1426797 TI - ["Historic" calcium antagonists and ischemic cardiopathy: critical review of the literature]. PMID- 1426798 TI - [The stunned and the hibernating myocardium after myocardial infarction]. PMID- 1426800 TI - Baroreceptor reflexes and sudden cardiac death: experimental findings and background. AB - The identification of subjects at high risk for sudden cardiac death is a key factor for an adequate preventive strategy. Relevant animal models may provide both a better understanding of the pathophysiologic mechanism involved and suggestions for a more precise risk stratification. Vagal hyperactivity is generally beneficial in the setting of acute myocardial ischemia. In a conscious animal model for sudden cardiac death, electric vagal stimulation markedly reduces the incidence of ventricular fibrillation (VF) in a high risk subgroup, whereas muscarinic blockade increases malignant arrhythmias in low risk animals. Among 192 dogs, those that develop VF during an episode of acute myocardial ischemia one month after myocardial infarction, have a significantly lower baroreceptor reflex sensitivity, compared to the survivors (9.1 +/- 6.0 vs 17.7 +/- 6.5 msec/mmHg, p < 0.0001). Furthermore, the analysis of vagal reflexes may identify high risk animals also before myocardial infarction. Therefore, the experimental studies indicate that the analysis of baroreceptor reflexes may be a powerful tool in the stratification of risk for sudden cardiac death. PMID- 1426799 TI - Ischemic modulation of myocardial innervation. AB - This article focuses on the interplay existing between the autonomic nervous system and the myocardium, with novel observations related to arrhythmogenesis. Myocardial ischemia and infarction produce an efferent denervation involving both limbs of the autonomic nervous system. As a consequence of the sympathetic denervation, the myocardial norepinephrine content is reduced to a major extent. As a logical consequence, this is followed by the phenomenon called "denervation supersensitivity", i.e. the tissue deprived of its nerve supply responds to the neural mediator in an exaggerated fashion. This is manifested by an exaggerated shortening of the effective refractory period during infusion of norepinephrine and by increased propensity for arrhythmias. With time, denervation is followed by reinnervation. An interesting counterpart of these findings is the possibility to document in patients after myocardial infarction if denervation has occurred using the MIBG technique. Not only efferent but also afferent denervation does occur and this might be involved in painless ischemia. In another series of studies we have provided the evidence that the pericardium is not a mere inert sac but it actively acts as a functional membrane. Pericardial prostaglandins released into the pericardial fluid alter electrophysiologic properties by modulating mostly the sympathetic effects; this may serve as a physiologic negative feedback control mechanism regulating sympathetic effects on the heart contributing to prevention of ischemic arrhythmias. PMID- 1426801 TI - Myocardial infarction and baroreflex sensitivity. Clinical studies. AB - Based on solid experimental evidence the concept has emerged that analysis of autonomic reflexes, and specifically of baroreceptive reflexes, might contribute to the identification of high risk subgroups in the post myocardial infarction phase. Accordingly, we brought this concept to clinical fruition and have performed the first clinical study to investigate the potential prognostic value of baroreflex sensitivity. The present article reviews those clinical results which indicate an almost 15 times greater risk for cardiac mortality among the patients with depressed baroreflex sensitivity. Baroreflex sensitivity has also been correlated with heart rate variability and it was found that the degree of correlation is relatively weak and such that it is not possible to predict one measure from the other. Thus, these two autonomic markers are not redundant. Among the various possibilities to induce favorable alterations in the autonomic balance, our group has selected and analyzed exercise training and the chronic administration of beta-blocking agents. Exercise training, examined in a case control study involving 70 patients, was found to increase baroreflex sensitivity by 30%. Beta-blockers were found to augment baroreflex sensitivity in 40% of the patients tested. As a logical evolution of these studies we have initiated a large prospective collaborative study destined to enroll 1200 post myocardial infarction patients and to assess the prognostic value of baroreflex sensitivity, of heart rate variability, and of traditional markers such as left ventricular ejection fraction and late potentials. PMID- 1426802 TI - Heart rate variability and the onset of tachyarrhythmias. AB - The autonomic nervous system plays an important role in the genesis of cardiac arrhythmias but the precise definition of this role is quite complex. The fluctuations of the heart rate may provide useful information about the balance of the autonomic nervous system. However, one obvious limitation is represented by extrapolating to the ventricle events which occur at the sinus node level. It has been clearly documented that atrial fibrillation of vagal origin is preceded by a progressive decrease in heart rate. On the other hand, ventricular arrhythmias of adrenergic origin are preceded by progressive heart rate acceleration and by diminution of vagally mediated short term changes. The absolute value in heart rate is less important than the actual trend in allowing inferences on the relative sympathetic or vagal predominance. A better understanding of the changes in the autonomic balance will provide a key for the mechanisms underlying several clinical events. PMID- 1426803 TI - [Guidelines for the diagnosis and evaluation of autonomic nervous system mediated syncope. Standards proposed by the Italian Association of Cardiostimulation and the Italian Group of Arrhythmology]. PMID- 1426804 TI - [Coronary angioplasty in postinfarct angina]. AB - BACKGROUND: The recurrence of transient myocardial ischemia is a frequent event in the course of acute myocardial infarction. Postinfarction angina develops more frequently after a non-Q wave infarction, and after effective thrombolysis; when uncontrolled by standard medical treatment, it is associated with an increased incidence of unfavorable cardiac events. Therapeutic strategies involve aggressive medical therapy, frequent use of early angiography, and mechanical coronary revascularization with bypass surgery or transluminal coronary angioplasty (PTCA). PATIENTS: We retrospectively examined 68 consecutive patients treated with PTCA for postinfarction angina. Of the whole, 36 (53%) had sustained a non-Q wave infarction; 29 (43%) had been treated with thrombolysis in the acute phase. Ischemia was in the infarction zone in 94% of cases; mean EF was 61.5 +/- 12%, and in 18 cases EF was < 55%. RESULTS: In 7 cases two arteries were dilated. There were no deaths related to the procedure. The overall success rate was 91.2%. Major complications occurred in 2 cases (1 acute occlusion with reinfarction, 1 major dissection requiring emergency surgery). The results are analyzed according to the time interval between index infarction and PTCA. In 28 cases (Group A) PTCA was performed within 30 days due to medically refractory symptomatology; in 40 cases (Group B) PTCA was postponed to beyond 30 days from infarction. In Group A involvement of the left anterior descending coronary artery was more frequent (75% of cases vs 40%; p = 0.009). The success rate in Group A was slightly lower than for Group B (85.7% vs 95%); the incidence of complications was higher (7.1% vs 0%), although not statistically different. At 6 month follow-up a restenosis was found in 10 cases (16% of successful PTCAs, 21% of angiographic controls). CONCLUSIONS: We conclude that for patients with postinfarction angina, selected for a suitable coronary anatomy, PTCA is an effective therapeutic option, with a high success rate, low immediate morbidity, and good mid-term results. The risk of intraprocedural complications appears only slightly higher for patients with unstable symptoms, who undergo PTCA earlier after infarction. PMID- 1426805 TI - [The electrocardiographic anomalies and 2D-echocardiographic findings during the recovery phase of the stress test in the postinfarct patient]. AB - BACKGROUND: The appearance or the increase of repolarization abnormalities in the EKG during post exercise (ET) recovery phase (R) is considered a marker of ischemia. METHODS: In order to evaluate the real meaning of these changes we compared the EKG data with eventual modifications of left ventricular kinesis analyzed by 2D-ECHO. 10 male patients with previous myocardial infarction, mean age 50 +/- 4.8 y, underwent exercise testing on a treadmill (Bruce's protocol) and continuous 2D-ECHO observation from the end of exercise along the whole R. Patients were divided in two groups: Group A (6 patients) and Group B (4 patients), all free of symptoms. RESULTS: Group A showed ischemic EKG markers during exercise which increased during R; Group B showed ischemic EKG markers only during R. The 2D-ECHO showed in Group A an impairment of left ventricular kinesis at peak exercise without increase or extension during R (WMSI at rest 1.32; peak ET 1.60; R 1.60); in Group B the kinetic alterations appeared only in R (WMSI at rest 1.33, peak ET 1.42; R 1.80), strictly related to EKG markers. CONCLUSIONS: The data suggest : 1) that the increase of EKG abnormalities already present during exercise do not seem to imply more severe ischemia; 2) that EKG changes appearing during R are markers of ischemia which occur in the R. PMID- 1426806 TI - [Coronary angioplasty without surgical standby: a prospective study]. AB - In 811 out of 1000 consecutive patients submitted to coronary angioplasty we elected not to arrange for surgical standby. All patients were informed, and accepted that in case of vessel occlusion an infarction might ensue, for which a conservative management was planned. This choice was made on the basis of a clinical and angiographic estimate of the possible consequences of vessel occlusion, or dictated by sound inoperability of the patient. Primary success was achieved in 700 patients (86%) and in 933/1026 lesions (91%). Fifty-six patients (6.9%) had an acute vessel occlusion (within 24 hours of the procedure), with Q or non Q-wave infarction in 24 cases (2.9% of patients). Emergency coronary stenting was performed in 9 patients. One patient had emergency bypass surgery 1 hour after the procedure, and another had urgent bypass surgery 24 hours after the procedure because of left main stem dissection: the former died despite surgery, the latter was discharged uneventfully. The remaining 7 in-hospital deaths (total mortality 1%) could not have been prevented by surgical standby: one patient died from electromechanical dissociation during the procedure, due to rupture of a ventricular pseudoaneurysm; another died after an uncomplicated procedure, due to an anaphylactic reaction to protamine; two others died suddenly 3 and 20 days, respectively, after a successful procedure; finally, three patients were "a priori" inoperable. Our data suggest that surgical standby is not necessary for a large number of angioplasty candidates, who can be identified on the basis of preliminary clinical and angiographic evidence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426807 TI - [Surgical standby during coronary angioplasty: a criterion to be modified?]. PMID- 1426808 TI - [Sotalol in the Wolff-Parkinson-White syndrome: an electrophysiological and clinical study]. AB - Distinctly different from the other beta-blocking agents, sotalol prolongs action potential duration in myocardial and Purkinje fibers, and increases atrial as well as ventricular effective refractory periods. Similarly, antegrade and retrograde accessory pathway refractory periods are increased by sotalol. The electrophysiologic and clinical effects of sotalol were studied in 40 patients (31 male and 9 female, mean age 32 +/- 14 years) with Wolff-Parkinson-White Syndrome (WPW). All patients had disabling episodes of supraventricular tachyarrhythmias (ST). Of the 40 patients, 15 (37%) had spontaneous recurrence of paroxysmal supraventricular reciprocating tachycardia (PSRT), 14 (35%) of atrial fibrillation (AF) and 11 (28%) of both PSRT and AF. All of the patients were non responders to serial transesophageal electropharmacological tests using I C class drugs. Sotalol 252 +/- 73 mg daily was administered, and, in steady-state, a new transesophageal study (TS) was performed to observe the re-induction of PSRT and/or AF. 34 patients (85%) were responders to TS (noninducibility of ST, or nonsustained ST or AF inducibility with an increase of 30% in the minimum R-R interval between pre-excitated beats during AF) and the results were confirmed during a follow-up of 17 +/- 9 months. In the non-responder group (5 patients), a I C class drug was associated with sotalol. One patient, who was a "non responder" to sotalol, sotalol + I C class drug, and to amiodarone, underwent surgical therapy. In the 26 patients (65%) who had episodes of PSRT (37%) or episodes of PSRT and AF (28%), it was impossible to reinduce PSRT in 85% of the cases. AF was induced at baseline in all of the studied patients, but after sotalol administration in 15 patients, it was impossible to reinduce AF. The rate of induced AF decreased from 208 +/- 39 beats/min to 156 +/- 36 beats/min (p < 0.001). The mean shortest R-R interval between pre-excitated beats increased from 214 +/- 35 (baseline) to 293 +/- 97 msec (sotalol steady state) (p < 0.001). No side effects were observed. A significant prolongation (p < 0.001) of the QTc interval was observed in all the patients after sotalol administration (from 0.39 +/- 0.2 to 0.42 +/- 0.02 sec.). On the basis of our results, we may conclude that sotalol has a potent effect on the antegrade refractoriness of the anomalous pathway and, in WPW syndrome at risk, is also effective in patients who don't respond to I C class drugs. PMID- 1426809 TI - [Paroxysmal atrial fibrillation in patients with chronic ischemic cardiopathy: a study of high-resolution atrial activation]. AB - BACKGROUND: Patients with ischemic heart disease and episodes of paroxysmal atrial fibrillation are at major risk of stroke. In order to prevent such episodes, through the identification of patients prone to atrial fibrillation, we investigated the high-resolution atriogram of 65 patients with chronic ischemic heart disease, 54 male and 11 female, mean age 60.22 +/- 9.04 years. Based on previous documented episodes of atrial fibrillation, the patients were divided into two groups: group A, 45 males and 3 females, mean age 58.92 +/- 7.68 years, without atrial fibrillation; group B, 9 males and 8 females, mean age 63.88 +/- 11.6 years, with atrial fibrillation. RESULTS: High resolution atrial duration (100-300 Hz) in group B (with atrial fibrillation) was higher than in group A (without atrial fibrillation) (140.59 +/- 16.85 ms vs 121.77 +/- 11.27 ms, p < 0.001); Non filtered atrial duration (0-300 Hz) was not different between the two groups, A and B (118.54 +/- 10.96 ms vs 123.53 +/- 18.77 ms, p = NS); The prevalence of late atrial potentials was higher in group B than in group A (60.8% vs 7.1%, p < 0.001); No relation was observed between high resolution atriogram data and echocardiographic measurements; Sensibility was 82%, specificity 81%, and predictivity 60%. CONCLUSIONS: Data from our study show that high resolution electrocardiography is a valid tool for identifying patients prone to atrial fibrillation. Such patients can be identified by the presence of "late atrial potentials" that, like late ventricular potentials for ventricular tachycardia, are correlated with atrial fibrillation. Nevertheless, a larger cohort of patients is necessary to confirm these results. PMID- 1426810 TI - [Persistent T-wave inversion in unstable angina: the correlation with the global and regional function of the left ventricle]. AB - The correlation between persistent negative T wave on basal electrocardiogram and coronary anatomy or global and regional left ventricular function was investigated in 34 patients with unstable angina defined as new onset (< 2 months), crescendo or rest angina. The patients with history of previous myocardial infarction, pathological Q waves on electrocardiogram or documented elevation of CPK were excluded. Eighteen patients (group A) showed T wave inversion (> 1 mV) in at least two leads on the basal electrocardiogram, persisting for at least 48 hours before coronary arteriography. In 16 patients (group B) the basal electrocardiogram was normal. Left ventricular volumes and ejection fraction were calculated and the regional systolic wall motion was analyzed using the area method in the 30 degrees right anterior oblique view. Hypokinesis was defined as more than 2 standard deviation below the mean value calculated in 24 normal subjects. No difference was present for age (A: 61 +/- 9 vs B: 57 +/- 9 yrs) and sex distribution. Critical stenoses of at least one coronary artery was documented in all but one patient (in group B). The number of critical stenosis per patient was equal (1.8) in the two groups. Left main coronary artery showed narrowing > 50% in three patients of group A and in two patients of group B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426811 TI - [Cardiologic emergencies: mortality and treatment. An analysis of 500 consecutive coronary events within the framework of the WHO-MONICA Project--Brianza Area. The Research Group of the WHO-MONICA Project--Brianza Area]. AB - Recently, a decreasing trend in cardiovascular mortality, starting from 1976-78, has been observed in Italy, particularly in northern regions. In order to explore one possible cause of the phenomenon, a survey of acute coronary care has been performed in a sample area, with about one tenth of the population of Lombardy, the largest and most developed northern Italian region. The survey has been carried out within the framework of the WHO-MONICA project: the treatment of 500 consecutive suspected coronary events in the age group 25-64 years, has been examined according to the international protocol. The following items have been investigated: time between onset of symptoms and medical intervention; characteristics of initial care; cardiac arrest and cardiopulmonary resuscitation in or outside the hospital; intensive care unit admission and length of stay; type of treatment before, during and after the event. Marked improvements have been accomplished in managing cardiac emergency. They have reduced in-hospital coronary mortality by more than 50%. However, several problems were still present at the time of the study, 1986-87: a) only 52% of patients obtained assistance within 4 hours (Tab III); b) cardiac arrest was practically always fatal outside the hospital and in 75% of the cases inside (Tab V); c) essential drugs, e.g. beta-blockers, were not so widespread and substantially absent were angioplasty and coronary bypass surgery (Tab IX). It has been estimated that improving adherence to optimal therapeutic standards might save more than 700 lives a year in Lombardy in the age group 25-65 years. PMID- 1426812 TI - [Pulmonary valve angioplasty via the jugular vein in a 73-year-old female patient]. AB - Percutaneous balloon valvuloplasty was successfully performed in a 73-year-old woman with severe congestive heart failure due to severe calcific valvular pulmonary stenosis. An approach by right internal jugular vein was used for the procedure. PMID- 1426813 TI - [Coronary embolism: a frequently forgotten cause of myocardial infarct and sudden death]. PMID- 1426814 TI - [The integration of nuclear medicine methods into cardiology: an operative proposal]. PMID- 1426815 TI - [The Ferrarese operative proposal on the integration of nuclear medicine methods into cardiology: what the cardiologist and the nuclear medicine specialist think. Interview by Michele Galli]. PMID- 1426816 TI - [In memoriam Oscar Marco Triulzi]. PMID- 1426817 TI - [Are antineutrophilic polymorphonuclear cytoplasmic antibodies pathogenic?]. PMID- 1426818 TI - [Digestive cancers in France. Comparison of the incidence in 7 departments and estimation of incidence in the entire country of France]. AB - Estimation of differences in the incidence of digestive cancers in France was made from incidence data coming from 7 French departments covered by population based registries. For some localizations, such as cancer of the pancreas, incidence variations could be explained by differences in recording techniques. But geographic variations clearly appeared for digestive tract cancers: the incidence of esophageal cancer is 4 to 5 fold less in the departments of Tarn and Haute-Garonne than in the department of Calvados. Conversely, the incidence of colorectal cancer is lower in the department of Calvados than in the others. For the entire country, the estimated number of digestive cancers is 46,300 cases per year. This number represents a third of all cancers in males and a fourth in females. Colorectal cancer (25,700 cases per year) is the most frequent of all cancers in both sexes. Cancer of the stomach (8,200 cases per year) is the second digestive cancer, equal to esophageal cancer in males. The heavy burden of digestive cancers in public health is emphasized by our results. These results should lead our country to intensify research in the direction of primary and secondary prevention. PMID- 1426819 TI - [Digestive lymphomatous polyposis]. AB - We report 7 prospectively followed cases of lymphomatous polyposis of the gastrointestinal tract. They were characterized by multiple polypoid lesions affecting several segments of the gastrointestinal tract always involving the colon and the rectum. An ileocecal mass was present in 4 cases. Regional lymph node involvement was constant. Peripheral lymphadenopathy was frequent (5 cases out of 7), as was other extra-digestive extension to the bone marrow (4 cases out of 7) and cavum (3 cases out of 7). The histopathological aspect was that of a small cleaved cells (working formulation) or centrocytic (Kiel classification) non-Hodgkin's lymphoma. The peculiar morphology and phenotype of the tumoral B lymphocytes suggest their possible follicle marginal zone origin. Lymphomatous polyposis bore a rapidly fatal prognosis in every case (mean survival 20 months). This study of seven patients together with the 20 well-documented cases of the literature confirms the existence of lymphomatous polyposis as a distinctive clinicopathological entity among gastrointestinal non-Hodgkin's lymphoma. PMID- 1426820 TI - Antineutrophil cytoplasmic autoantibodies in inflammatory bowel diseases. AB - Antineutrophil cytoplasmic autoantibodies have been recently reported in sera from patients with inflammatory bowel disease. We report our experience based on 90 patients with ulcerative colitis, 148 patients with Crohn's disease, and 60 controls. Determination of antineutrophil cytoplasmic autoantibodies was performed by the indirect immunofluorescence technique on ethanol fixed leucocytes. The specificities for proteinase 3, myeloperoxidase, and lactoferrin were tested by enzyme-linked immunosorbent assay. Forty-three out of 90 (48%) patients with ulcerative colitis, 10 out of 148 (7%) patients with Crohn's disease, and none of controls were positive by indirect immunofluorescence technique. All patients but two with positive immunofluorescence exhibited a perinuclear staining pattern. Among patients with ulcerative colitis, there was no relationship between the presence of perinuclear antineutrophil cytoplasmic autoantibodies and disease location or activity. Seven out of 20 (35%) patients with ulcerative colitis who had a previous colectomy (including 1 with ileoanal anastomosis) had perinuclear antineutrophil cytoplasmic autoantibodies. Antineutrophil cytoplasmic autoantibody specificity was not directed against myeloperoxidase, proteinase 3 or lactoferrin in sera from patients with inflammatory bowel diseases. Inflammatory bowel diseases are associated with a new subset of antineutrophil cytoplasmic autoantibodies. Among patients with Crohn's disease and ulcerative colitis, the sensitivity and specificity of the presence of perinuclear antineutrophil cytoplasmic autoantibodies for ulcerative colitis was 46% and 93%, respectively. Their presence reinforces the likelihood of underlying immunologic dysregulation in ulcerative colitis. Identification of the autoantigen(s) to which these antibodies are directed might facilitate the understanding of inflammatory bowel disease pathophysiology. PMID- 1426821 TI - [Viral hepatitis A: a changing epidemiology leading to a change in concepts]. PMID- 1426822 TI - [High prevalence of hepatitis B after heart transplantation: absence of evidence for transfusional transmission]. PMID- 1426823 TI - [Seroepidemiology of hepatitis A in six departments in West-Central France in 1991]. AB - Antibodies to hepatitis A virus were sought for among residents of 6 "departements" of West-Central France during a routine medical check up provided by the national health insurance system to all affiliated persons. Among them 5,641 subjects (aged 6 to 60) were randomly selected to a sample size of 256 +/- 15 male or female subjects for each five-year age group. Anti-HAV were detected in 51% of the screened population. The prevalence was less than 5% in the 6-15 age group and increased by successive steps to exceed 90% in the subjects over 50. The highest increase was observed between the 26-30 (39%) and the 31-35 (57%) age groups. This study confirms the influence of socio-economical factors on the anti-HAV prevalence rate. Factors such as profession or scholar education were previously known, but the housing conditions and especially the number of siblings were identified in our present report. In relation to this low prevalence of anti-HAV among young adults, one may fear an increase of overt hepatitis cases which are known to be more frequent in adults than in infants or children. Moreover any break in hygiene may expose the population to an epidemia. Only active immunization with a vaccine against hepatitis A could efficiently prevent these individual and community-related risks. PMID- 1426824 TI - [Hemodynamic effects of the administration of terlipressin alone or combined with nitroglycerin in patients with cirrhosis]. AB - Terlipressin (Glypressin), a synthetic analog of vasopressin, induces arteriolar vasoconstriction which causes both a portal hypotensive effect and certain side effects on the systemic circulation (elevated arterial pressure and reduced cardiac output). The combination of nitroglycerin with terlipressin might accentuate the portal hypotensive effect and prevent the side-effects on the systemic circulation. The aim of this study was to examine the systemic and splanchnic hemodynamic responses to terlipressin administered alone or combined with nitroglycerin in patients with cirrhosis. Systemic and splanchnic hemodynamics were measured before and 1 h after a bolus of terlipressin (1 to 2 mg IV) given alone (n = 10) or in association with nitroglycerin infusion (25 micrograms/min, n = 9). Terlipressin alone significantly increased the arterial pressure by 21%, systemic vascular resistance by 60%, and significantly decreased cardiac output by 23%. The right atrial and pulmonary pressures significantly increased and the wedged hepatic venous pressure and hepatic venous pressure gradient significantly decreased by 8% and 16%, respectively. The combined therapy decreased the cardiac output by 20%, but did not significantly modify the other systemic and splanchnic hemodynamic values. No significant differences were found between terlipressin and the combined therapy concerning changes in wedged hepatic venous pressure or hepatic venous pressure gradient. We conclude that in patients with cirrhosis, nitroglycerin prevents the deleterious vasoconstrictor and vasopressor effects of terlipressin. However, the combined therapy, as terlipressin alone, decreases the cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426825 TI - [Effect of acute administration of acamprosate on the risk of encephalopathy and on arterial pressure in patients with alcoholic cirrhosis]. AB - To evaluate the risk of hepatic encephalopathy and arterial hypotension in cirrhotic patients after acute administration of acamprosate, a GABA mimetic drug used in the weaned alcoholic, a randomized double-blind trial was conducted in 24 cirrhotic patients with low or moderate hepatic insufficiency (Pugh grade A or B). Twelve patients received 666 mg (2 tablets) of acamprosate and 12 received placebo. The 2 groups were similar before treatment, except for a male predominance in the acamprosate group. Tested parameters were the P100 latency of visual evoked potentials using a checkerboard pattern reversal as stimulus, the number connection test and the arterial blood pressure in upright and recumbent positions. The two first parameters were studied before and 2 hours after treatment. Blood pressure was recorded every half hour during 6 hours. No significant effect on the development of subclinical hepatic encephalopathy was noted. Nevertheless, even if some authors disagree with the GABA hypothesis of hepatic encephalopathy, it is possible that the dose was too low to induce subclinical hepatic encephalopathy. A study with more prolonged treatment could be necessary to be sure of the drug's safety in these patients. On the other hand, a transient decrease of diastolic arterial blood pressure was observed without significant systolic blood pressure modification. These results suggest that a moderate dose of acamprosate does not induce subclinical encephalopathy, but transient diastolic hypotension. PMID- 1426827 TI - [Infection of ascitic fluid by perforation of a sclerodermic colon]. AB - In progressive systemic scleroderma, a disease of protean manifestations, involvement of the gastrointestinal tract is noted infrequently in patients who are asymptomatic, and is rarely fatal. We report the case of a 65-year-old woman who was admitted for ascitis related to a non A, non B cirrhosis. The patient presented with bacterial peritonitis due to colonic perforation by fecal impaction associated with sclerodermic involvement. Pathologic study of the resected colon showed that the true muscularis was very atrophic and fibrotic, characteristic of scleroderma. To our knowledge, this cause of ascitic fluid infection has not been previously reported. PMID- 1426826 TI - [Prophylaxis of infectious complications by selective digestive bacterial decontamination in patients with cirrhosis]. PMID- 1426828 TI - [Cystadenoma of the extrahepatic bile ducts: a rare cause of cholestasis]. AB - We report the case of a 45-year-old woman who underwent laparotomy for obstructive jaundice due to an uncommon cystic tumor located in the porta hepatis. Histology of the resected specimen disclosed a cystadenoma of the common hepatic duct. A review of 20 reported cases shows that the preoperative diagnosis is uncommon; wide resection appears to be the treatment of choice since these lesions are susceptible of local recurrence and malignant change. PMID- 1426829 TI - [Leiomyosarcoma of the inferior vena cava invading into the liver. Complete resection with venous reconstruction]. AB - A case of leiomyosarcoma of the retrohepatic inferior vena cava associated with metastasis in the right liver lobe is reported. Resection included extended right hepatectomy, right nephrectomy, and tumor--containing inferior vena cava resection followed by polytetrafluoroethylene tube reconstruction. A comfortable survival was obtained before multifocal malignant spread led to death 42 months after surgery. PMID- 1426830 TI - [Biomedical research, Huriet's law and non-university-affiliated hospital]. PMID- 1426831 TI - [Acute rhabdomyolysis and necrotizing enterocolitis after ingestion of fenoverine]. PMID- 1426832 TI - [Endoscopic removal of an intra-uterine device from the sigmoid colon]. PMID- 1426833 TI - [A new computed tomography classification of acute pancreatitis]. PMID- 1426834 TI - [Autoimmune hepatitis type 1 revealed during treatment with interferon]. PMID- 1426835 TI - [Cholecystectomy by celiosurgery and cancer of the gallbladder]. PMID- 1426836 TI - [Acute hepatitis probably secondary to the treatment with pyrimethamine sulfadiazine combination]. PMID- 1426837 TI - [Late jaundice after cholecystectomy by laparoscopy, caused by a endo-choledochal clip]. PMID- 1426838 TI - [Prevention of colorectal cancer: what is the role of aspirin?]. PMID- 1426839 TI - [What is the role of rectosigmoidoscopy in the early diagnosis of colorectal cancer?]. PMID- 1426840 TI - [Portal colonopathy: a new entity in the course of portal hypertension]. PMID- 1426842 TI - Graded compression sonography of abdominal neoplasms mimicking acute appendicitis. AB - Over a 3-year period nine patients (mean age of 43 years) with acute abdominal pain and unsuspected abdominal neoplasms were referred for graded compression sonography to rule out appendicitis. Six of the nine patients had right lower quadrant neoplasms involving the cecum, terminal ileum, iliacus muscle, or iliac lymph nodes. However, in three patients neoplasm was noted outside the right iliac fossa involving the liver, right kidney, and upper abdominal mesentery. This study underscores the fact that in patients without sonographic evidence of acute appendicitis, a survey of the upper abdomen and right flank should routinely be performed in addition to scanning the right iliac fossa and pelvis. In patients more than 50 years of age neoplasm must also be kept in mind in the differential diagnosis of appendicitis. PMID- 1426841 TI - Acute abdomen of unknown origin: impact of CT on diagnosis and management. AB - A prospective study was performed including 40 patients with an acute abdominal syndrome presenting difficulties in defining the etiology. All patients underwent an emergency computed tomographic (CT) scan. The CT scan made the syndrome's diagnosis in 95% of cases and it permitted the detection of a lesion in 57.5% of cases. The diagnostic impact of CT scan was significant (p less than 0.01). The value and the specific contribution of CT in various diseases were analyzed. CT allowed appropriate therapeutic decisions in 95% of cases where clinical examination performance was positive in only 60% of cases. We had two negative CT results leading to an inappropriate therapeutic decision; it consisted of two cases of undiagnosed appendicitis. CT modified the primary therapeutic strategy in 30% of cases and avoided seven laparotomies. PMID- 1426843 TI - Fast spin-echo imaging of the abdomen during breath-holding: an alternative to RASE and other fast imaging techniques. AB - We have developed a rapidly acquired T1-weighted spin-echo pulse sequence that uses gradient echo-like parameters of TR 70 ms, TE 10 ms, NEX-1 (SE 70/10/1) with large pulse angles, and presaturation. This sequence yields two images of the abdomen during a comfortable breath-hold of 9 s. Preliminary phantom studies with this sequence demonstrated that peak signal-to-noise ratios occurred at pulse angles of 120 degrees and 135 degrees. Compared to this rapidly acquired sequence, a conventional T1-weighted spin-echo sequence of TR 140 ms, TE 10 ms, NEX-4 demonstrated 2.8 times the signal-to-noise ratio, 2.6 times the liver spleen contrast-to-noise ratio but only 1.6 times the contrast-to-artifact ratio. When normalized for the imaging time, however, there was little difference in the signal-to-noise and contrast-to-noise ratios, although the SE 70/10/1 demonstrated 2.0 times the contrast-to-artifact ratio. We conclude that for abdominal imaging the SE 70/10/1 is an excellent alternative to RASE and other fast imaging techniques, and, although there are inherently low signal-to-noise ratios, it may be particularly useful when coupled with a paramagnetic contrast agent. PMID- 1426844 TI - Gd-DTPA as an intestinal contrast agent for MR imaging of the lower abdomen: phase III clinical trial. AB - Thirty-one patients were investigated with magnetic resonance (MR) imaging of the lower abdomen before and after the administration of gadopentetate dimeglumine (Gd-DTPA) solution per os or per rectum or from both routes for the opacification of the intestinal tract. The parameters evaluated were: (a) contrast medium distribution, (b) degree of filling of the bowel lumen, (c) contrast between the bowel lumen and the surrounding normal or pathological structures, and (d) whether the administration of the contrast agent improved the diagnostic ability of MR compared to computed tomography (CT) or plain MR of the same region. Gd DTPA, at a concentration of 1 mmol/L, produced a positive signal irrespective of its dilution in the bowel and good contrast between the bowel lumen and the adjacent tissues or any possible pathological lesions. From the diagnostic point of view, after the administration of contrast medium, MR is comparable to CT and much superior to plain MR. It is concluded that opacification of the bowel with Gd-DTPA solution will improve the diagnostic yield of MR imaging of the lower abdomen. PMID- 1426845 TI - Assessment of distant metastases with ultrasound-guided fine-needle aspiration biopsy and cytologic study in carcinoma of the esophagus and gastroesophageal junction. AB - The use of ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) for the assessment of distant metastases was prospectively studied in 135 consecutive patients with carcinoma of the esophagus and gastroesophageal junction. Patients with accessible lesions on US and computed tomographic (CT) studies of the supraclavicular regions and the abdomen underwent US-guided FNAB. In patients with multiple lesions biopsies were preferentially performed on enlarged supraclavicular nodes. Forty-nine patients underwent US-guided FNABs of 53 lesions. A cytologic diagnosis was established in 46 of 53 (87%) biopsies. Seven of 53 (13%) biopsies were nondiagnostic. Distant metastases were diagnosed by means of cytologic study in 33 of 135 (24%) patients. Supraclavicular metastases were diagnosed in 22 patients and abdominal metastases were diagnosed in 12 patients, including one patient who also had supraclavicular metastases. US guided FNAB can improve the selection of patients for surgical and nonsurgical treatment by diagnosing distant metastases in an important number of patients. PMID- 1426846 TI - Inflammatory myofibrohistiocytic proliferation presenting as giant gastric pseudotumor. AB - A 5-year-old boy presented with refractory microcytic anemia, growth failure, and markedly elevated sedimentation rate. Computed tomographic (CT) and upper gastrointestinal study disclosed an ulcerated 9-cm large gastric mass, which proved to be an inflammatory myofibrohistiocytic proliferation (IMP). The characteristic clinical and radiologic features of this rare entity are herein reviewed. PMID- 1426847 TI - Embolotherapy of massive duodenal hemorrhage. AB - Eleven patients with massive duodenal hemorrhage were treated by emergent embolization. Bleeding originated from duodenal ulcer in three patients, from duodenal tumor in one, from ruptured pancreaticoduodenal artery pseudoaneurysm in three, and from ruptured gastroduodenal artery pseudoaneurysm in four. Complete hemostasis was obtained immediately after embolotherapy in all cases. Three of these patients died during the hospitalization period, one of whom from duodenal infarction and pancreas necrosis induced by embolization. In three patients with duodenal ulcer, complete hemostasis was obtained only by the gastroduodenal artery embolization with Gelfoam particles. Seven patients with pseudoaneurysms of the gastroduodenal artery or its branches required not only blockage of blood flow from the celiac artery but also the superior mesenteric artery for complete hemostasis. Therefore, in patients presenting with duodenal hemorrhage, the possibility of dual blood supply to the duodenum should be considered. Emergent embolization represents a useful alternative to surgery for massive duodenal hemorrhage, but it carries a risk of complications in patients with previous gastroduodenal surgery or significant visceral atherosclerosis. PMID- 1426848 TI - Successful arterial embolization of arteriovenous fistula in the portal circulation. AB - We successfully performed arterial embolization of an arteriovenous fistula between the left gastric artery and vein. The increased blood flow in the portal vein via the left gastric vein and the arteriovenous fistula induced severe portal hypertension. After obliteration of the left gastric artery, the arteriovenous fistula was not opacified on angiography and the portal hypertension improved. PMID- 1426849 TI - Radiographic features in ischemic jejunoileitis: serial changes and comparison with pathologic findings. AB - Serial radiographic examinations of the small intestine, including double contrast studies, were performed in 13 patients with ischemic jejunoileitis, nine with the stricturing form and four with the transient form. Thumbprinting was observed in five (38%) patients and thickening of the folds in four (31%) at the acute stage of the disease. Tubular narrowing with irregular contours and dilated proximal bowel was observed in six (46%) patients and appeared on day 27 or later. Pathologic findings of the resected specimen in eight patients with the stricturing form revealed annular stricture with relatively shallow ulcers; the irregular contours of the tubular narrowing on radiographs were consistent with a granular or nodular appearance and/or multiple fissures on pathologic study. Eccentric deformity and sacculation were demonstrated in only one patient with the stricturing form. In addition, double-contrast study revealed small ulcers in three (23%) patients. Our results indicate that radiographic findings accurately reflect the clinical course and pathologic findings in this disease. PMID- 1426850 TI - Retractile mesenteritis with colon and retroperitoneum involvement: CT findings. AB - We report a case of retractile mesenteritis which involved the rectosigmoid colon and extended into the retroperitoneum with ureteral obstruction. These complications are rare. The radiological features [including computed tomography (CT)] are described. PMID- 1426851 TI - Effectiveness of pneumatic reduction of ileocolic intussusception in children. AB - A total of 158 consecutive therapeutic air enemas were performed upon 133 patients during a 2-year period. Perforation and/or an impairment of the general condition of the children were the only main contraindications for the reduction attempt (five patients). Successful reductions were achieved in 89% of cases with no complications. Operation was performed in all 17 cases of unsuccessful reduction: resection in four cases, easy manual reduction in nine, difficult manual reduction in two, and spontaneous reduction in two. There were 16 (12%) patients with one or more recurrent episodes. In 23 (16%) cases, following pneumatic reduction, a swollen ileocecal valve showing a multiple appearance was observed. This fact sometimes results in a differential diagnosis with incomplete reduction; in all these cases, small bowel aeration was always a sign of complete reduction. No significant difference was noted between a swollen ileocecal valve and patient age, duration of symptoms, presence of small bowel obstruction, and further recurrences. Air enema has improved our previous success obtained with hydrostatic reduction (79%), as well as being a simpler, cleaner, and faster technique for intussusception reduction in children. PMID- 1426852 TI - Benign colorectal neoplasms undetected by colonoscopy. AB - This retrospective investigation assessed the sensitivity of colonoscopy for the detection of colonic polyps seen previously at barium enema examination. Included in the study were 77 patients with 106 polypoid lesions. Films showing lesions not subsequently seen at colonoscopy were reviewed and only those lesions with a visible point of attachment, exhibiting no movement in response to filling or change in position of the patient, and confidently diagnosed as a polyp by both reviewing radiologists were included among the 106 lesions. Sixteen lesions (15%) seen radiologically were not located colonoscopically, indicating an endoscopic sensitivity of 85%. Contrary to previous reports, most of the lesions missed endoscopically were in the left colon in regions thought to have been traversed by the instrument. The 15% false-negative rate found for colonoscopy is consistent with existing reports on colonoscopic errors and is approximately the same as the false-negative error rate for radiologic detection of colonic polyps. PMID- 1426854 TI - Extracapsular (satellite) hydatid cysts. AB - Sixteen percent of hydatid cysts in the liver in 185 patients examined by computed tomography (CT) showed daughter cysts located exterior to the fibrinous membrane of the main hydatid cysts. We call these extracapsular or satellite cysts. Extracapsular cysts have the same appearance as endogenous daughter cysts. Preoperative demonstration of these cysts is useful for planning an appropriate surgical treatment and reduction of the recurrence rate. PMID- 1426853 TI - Bile duct disease: prospective comparison of ERCP, CT, and fat suppression MRI. AB - The authors compared computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP), techniques commonly used to study the biliary tree, with pre- and post-Gd-DTPA breath-hold fast low angle shot (FLASH) and fat suppressed spin-echo in 28 consecutive patients with bile duct abnormalities detected on ERCP, including 11 patients with malignant disease and 17 patients with benign disease. ERCP, CT, and magnetic resonance (MR) images were prospectively interpreted in a blinded fashion and reviewed by consensus. ERCP characterized all cases of malignant disease by the presence of a narrowed bile duct lumen with irregular margins. CT and MRI detected all cases of malignant disease and characterized nine of 11 as malignant. In seven of these cases, CT and MRI showed thickening of extrahepatic bile duct walls greater than 5 mm. MRI images showed intrahepatic-enhancing periportal tissue in four cases, which was not seen on CT images, and which was biopsy-proven tumor extension. Benign disease was characterized on ERCP images by the demonstration of smooth tapered narrowings in 16 cases, whereas on CT and MR images it was characterized by mild to moderate dilatation of the intrahepatic bile ducts and wall thickness less than 5 mm in 13 cases. Overall ERCP correctly characterized 27 cases as benign or malignant and CT and MRI both characterized 25. The results of this study show a trend that ERCP is superior to CT and MRI for characterizing bile duct disease. PMID- 1426855 TI - Significance of serum sialic acid in patients with Crohn's disease. AB - Serum sialic acid was measured to evaluate the activity of Crohn's disease. The sialic acid levels of patients with Crohn's disease in remission (CRP 0.0 mg/dl) were significantly higher than those of healthy subjects and postoperative patients with Crohn's disease. In patients in remission, serum sialic acid was significantly correlated with hemoglobin, hematocrit, platelet, and rapid turnover protein. Correlations with platelet, retinol-binding protein, and prealbumin were especially strong. From these findings, it was concluded that serum sialic acid level provides a useful index of the activity of Crohn's disease. PMID- 1426856 TI - IgG subclass-containing cells around the lymph follicle in the human intestine. AB - The authors previously reported the ring-like distribution of IgG-containing cells around the lymph follicle in both the small and large intestine. In the present study, the distribution of IgG subclass-containing cells around the lymph follicle was examined in both the small and large intestine, including Peyer's patches, by the indirect immunoperoxidase staining method. A ring-like distribution of IgG subclass-containing cells was observed in 14 out of 21 lymph follicles including 4 Peyer's patches (66.7%) in the terminal ileum, and 4 out of 7 (57.1%) in the large intestine. The percentages of IgG1-, IgG2-, IgG3-, and IgG4- containing cells around the lymph follicle in the terminal ileum were 27.6 +/- 11.6%, 51.9 +/- 15.4%, 16.5 +/- 10.2%, and 4.0 +/- 3.1%, respectively, and those in the large intestine were 22.9 +/- 15.4%, 47.4 +/- 14.9%, 11.2 +/- 4.1%, and 18.5 +/- 7.7%, respectively. Thus, among the IgG subclasses, IgG2-containing cells showed the most frequent ring-like distribution around the lymph follicle. The IgG2 predominance around the lymph follicle in the intestine was markedly different from reported IgG1 predominance in the lamina propria in the large intestine. This difference in IgG subclass distribution may suggest different origins of the IgG subclass-containing cells in the lamina propria and in areas around the lymph follicle. PMID- 1426857 TI - In situ characterization of mononuclear cell phenotype in intrahepatic lymphoid follicles in patients with chronic viral hepatitis. AB - The author examined liver biopsy specimens obtained from 596 patients with chronic viral hepatitis to clarify the role of lymphoid follicle formation in the portal spaces. Lymphoid follicles were observed more frequently in chronic hepatitis non-A non-B than in chronic hepatitis B and were also common in patients with anti-hepatitis C virus-positive non-A non-B hepatitis. Immunohistology revealed that these hepatic lymphoid follicles resembled the lymphoid follicles of synovial tissue in rheumatoid arthritis. In situ hepatitis B virus markers were examined in 40 patients with chronic hepatitis B showing lymphoid follicles. Among these, hepatitis B surface antigen (HBsAg) was detected in liver cells as well as in the center of the follicles in 19 patients (47.5%). By immune electron microscopy, the author confirmed the HBsAg-positive cells in the lymphoid follicles as follicular dendritic cells. These cells appeared to be a site for antigen trapping in the follicles, therefore, the intrahepatic lymphoid follicles are suggested to play a role in immune response to HBsAg in chronic hepatitis B. PMID- 1426858 TI - Spontaneous bacterial peritonitis due to Clostridium perfringens in a patient with liver cirrhosis and pure red cell aplasia. AB - A 63-year-old man with decompensated liver cirrhosis and pure red cell aplasia complained of pyrexia, abdominal distention and abdominal pain. A diagnosis of spontaneous bacterial peritonitis (SBP), Conn's syndrome, was made upon the isolation of an anaerobe Clostridium perfringens from both ascitic fluid and peripheral blood. The bacteria were found to be susceptible to piperacillin, and administration of the antimicrobial agent markedly improved his SBP. The anaerobes should be kept in mind as one of the possible pathogens of SBP, although anaerobic infection has been reported to be quite rare in the disease. PMID- 1426859 TI - Intrasplenic pancreatic pseudocyst: a case report. AB - An intrasplenic pseudocyst associated with the acute relapsing phase of chronic pancreatitis in a 51-year-old woman is reported, with a review of the Japanese literature. The patient was admitted with a complaint of left lateral and back pain. Abdominal US and CT revealed communicating cysts at the pancreatic tail and the subcapsule of the spleen. A repeat US and CT 1 month after admission demonstrated enlargement of the cyst at the pancreatic tail. ERCP revealed a dilated main pancreatic duct without any definite evidence of stenosis, and direct communication with the cyst at the pancreatic tail. Percutaneous cystography revealed that the subcapsular cyst of the spleen, the cyst of the pancreatic tail, and the main pancreatic duct communicated with each other. The cyst contained serous fluid with an amylase content of 57,500 IU/I. Distal pancreatectomy and splenectomy was performed. Histologically, there was a nonepithelial lining on the inner surface of the cysts at the pancreatic tail and the subcapsule of the spleen. Severe chronic inflammatory changes were present in the resected tail of the pancreas. Timely surgical treatment is advocated to reduce the mortality and morbidity associated with complications of intrasplenic pseudocysts. PMID- 1426860 TI - Anti-neutrophil cytoplasmic autoantibodies in inflammatory bowel diseases (IBD). PMID- 1426861 TI - Serial changes in renal function during laparoscopic cholecystectomy. PMID- 1426862 TI - Hepatitis E: review. AB - Hepatitis E is endemic, often provoking epidemics in many developing countries. It resembles hepatitis A clinically and epidemiologically but show a higher mortality rate and less infectiousness. Several lines of evidence strongly support the assumption that humans become immunized once they contract hepatitis E. Because of the low infectiousness, most of the adult population of endemic areas are susceptible to hepatitis E until an epidemic occurs, although they are almost always infected with hepatitis A during infancy. Epidemics are caused by accidental contamination by the hepatitis E virus (HEV) in feces of water provided to these people. The liver change reveals necroinflammation related to the immune-mediated mechanism. The HEV is molecularly cloned and sequenced and has a single-stranded, positive-sense RNA genome, 7,194 nucleotides followed by a poly (A) tail. There are three open reading frames. The non-structural gene, approximately 5 kb is located at the 5' end, while the structural gene, approximately 2 kb is located at the 3' end of the genome. There is a low level of nucleotide variations among HEV strains isolated from Myanmar and China and a single serotype appears to exist. The HEV may be a new RNA virus or belong to Caliciviridae family. Further investigation include in vitro propagation, elucidation of the gene replication, global seroepidemiology and vaccination of the HEV. PMID- 1426863 TI - Transforming growth factor alpha receptor binding sites in the canine gastrointestinal tract. AB - Transforming growth factor alpha (TGF-alpha) interacts with the same plasma membrane receptor as epidermal growth factor and is likely to play a role in proliferative and trophic processes of gastrointestinal tissues. The distribution of receptor binding sites for TGF-alpha was examined in the canine gastrointestinal tract (distal esophagus, stomach fundus, descending duodenum, jejunum, ileum, transverse colon) by tissue section autoradiography. 125I-TGF alpha yielded a labeling pattern comparable to that of 125I-epidermal growth factor. Specific binding sites were particularly abundant in the mucosa in each region, with the highest concentration in the esophagus, colon, and stomach, as assessed by computer assisted densitometry. The density of binding sites was moderate in the stomach muscularis mucosae, low in the external muscle layer, and very low to undetectable in the submucosa throughout the gastrointestinal tract. In most cases, the greatest density within the individual regions was detected in the area characterized by the highest proliferative rate. Lymphoid aggregates were not labeled. In conclusion, TGF-alpha receptor binding sites are present throughout the gastrointestinal tract with differential patterns in the various regions; they are principally distributed to the mucosa and predominantly located to proliferative cell areas. These results are consistent with a role of this factor in regional regulation of proliferation and differentiation in the gut. PMID- 1426864 TI - Shaking of the intact rat and intestinal angulation diminish the jejunal unstirred layer. AB - A sizeable pre-epithelial diffusion barrier (unstirred layer) is present during perfusion of the rat jejunum. In the present study, three rapidly transported compounds, CO, [14C]warfarin, and glucose (5.5 mmol/L), were used as probes to assess the ability of manipulations to reduce the unstirred layer. This layer was 700-800 microns thick in a 30-cm jejunal segment perfused in conventional fashion on the abdominal wall. Placement of four sharp angulations in the segment or replacement in the abdominal cavity reduced the maximal unstirred layer to 200 400 microns. Increasingly rapid shaking of the anesthetized, intact rat on a platform shaker produced progressively thinner unstirred layers. At 250 revolutions per minute, the maximal layer ranged from 32 to 68 microns for the three probes and may have been appreciably less if the epithelium offered appreciable resistance. Shaking yields a > 15-fold reduction in unstirred layer resistance and provides a means for measuring this resistance and for obtaining more accurate assessment of the true in vivo transport Michaelis constant (Km) of any compound. PMID- 1426865 TI - Importance of gastric acid in gastric ulcer formation in rabbits with antibody induced prostaglandin deficiency. AB - The role of gastric acid in the development of gastroduodenal ulcers in prostaglandin-deficient conditions is unclear. In the current study, the effect of the proton pump inhibitor omeprazole on the formation of gastric ulcers was examined in a previously validated rabbit model of antibody-induced prostaglandin deficiency. Intragastric administration of 20 mg/kg omeprazole every 12 hours caused a profound suppression of gastric acidity (i.e., pH above 5 continuously). This same dose of omeprazole significantly reduced gastric ulcer formation induced by passive immunization with 6-keto-prostaglandin F1 alpha antibodies. It is concluded from these observations that gastric acid plays a critical role in the formation of gastric ulcers in rabbits with antibody-induced prostaglandin deficiency. PMID- 1426866 TI - Surface hydrophobicity of gastric mucosa in Helicobacter pylori infection: effect of clearance and eradication. AB - Surface hydrophobicity of the gastric mucosa is reduced in peptic ulcer disease and Helicobacter pylori infection. This abnormality may be caused by H. pylori or may be an inherent defect. The aim of the present study was to clarify the relationship between H. pylori infection and mucosal hydrophobicity by examining the effect of eradication of the organism. H. pylori-positive patients with (n = 42) or without (n = 42) duodenal ulcer were randomized to receive ranitidine, bismuth, or bismuth plus antibiotics. Surface hydrophobicity of gastric mucosa was assessed by measurement of plateau-advancing contact angle. Measurements were performed at presentation, end of treatment, and 1 month later. Contact angle was unchanged after ranitidine (55 degrees vs. 56 degrees) but increased with bismuth (57 degrees-62 degrees; P < 0.05) and bismuth plus antibiotics (56 degrees-67 degrees; P < 0.0001). One month after treatment ended, contact angles in patients in whom H. pylori was not eradicated were not different from those before treatment (56 degrees vs. 56 degrees) but increased to a value similar to H. pylori-negative controls in patients in whom H. pylori was eradicated (56 degrees 69 degrees; P < 0.0001). It is concluded that reduced mucosal hydrophobicity in peptic ulcer disease is secondary to H. pylori infection and that this impaired mucosal defense provides a possible mechanism whereby H. pylori infection predisposes to acid/peptic digestion. PMID- 1426867 TI - Adrenergic blockage does not restore the canine gastric migrating motor complex during vagal blockade. AB - Bilateral cervical cooling blockade of the vagi abolishes the gastric migrating motility complex (MMC), except for the pylorus. The present study investigated if this finding is caused by adrenergic inhibition of the stomach via sympathetic nerves entering the vagi below the level of the blockade. Stomach and upper small bowel motor activity was monitored in five chronic dogs whose vagosympathetic nerve trunks were previously isolated in bilateral, cervical skin loops to permit blockade by cooling. Adrenergic blockade was performed by an initial bolus injection of phentolamine (0.3 mg/kg) and propranolol (0.3 mg/kg) followed by a continuous intravenous infusion of the combined drugs at a rate of 1.5 mg.kg-1.h 1 for phentolamine and 0.3 mg.kg-1.h-1 for propranolol. Bilateral cervical vagal blockade abolished the gastric MMC, with persistence of phase III of the MMC in the upper small bowel. During combined vagal and adrenergic blockade, gastric contractions were absent in 4 of the 22 duodenal complexes observed. In the other duodenal complexes, intermittent gastric contractions were associated with all phases of the intestinal MMC, including phase I. At times, this contractile activity was accentuated during phase III but never reached the intensity of activity or showed the typical coordination features of the gastric MMC seen with the vagi intact. Therefore, unopposed adrenergic inhibition of the stomach does not explain the absence of the gastric MMC during vagal cooling blockade. Under normal circumstances, the vagus nerve is the most important pathway for central control of the appearance of the gastric MMC. PMID- 1426868 TI - Currently used doses of omeprazole in Zollinger-Ellison syndrome are too high. AB - The efficacy of omeprazole increases during the first few days of administration, suggesting that long-term maintenance dose requirements in patients with Zollinger-Ellison syndrome may be lower than those initially established by upward titration. Long-term maintenance doses of omeprazole were prospectively reduced in 37 patients who had been taking omeprazole for 22 +/- 4 months. Successful reduction was defined as reduction to 20 mg once or twice daily with an absence of symptoms, endoscopy without evidence of active acid-peptic disease, and a gastric acid output of < 10 mEq/h. Sixty-eight percent of patients (25/37) were successfully reduced to 20 mg of omeprazole once (18/24) or twice daily (7/13). Ninety-five percent of patients (20/21) without multiple endocrine neoplasia type I, severe gastroesophageal reflux disease, or previous partial gastrectomy had safe reductions of doses. It is concluded that the currently used omeprazole maintenance doses in patients with Zollinger-Ellison syndrome are too high and advocated that the initial dose still be established by acute daily upward titration followed by gradual reduction once control of acid output has been achieved. PMID- 1426870 TI - Gliadin immune reactivity is associated with overt and latent enteropathy in relatives of celiac patients. AB - Antigliadin antibodies have been widely used in the screening of celiac disease. Using this test, candidates for jejunal biopsy were selected from 328 first degree relatives of 128 adult celiac patients. All relatives geographically available were willing to participate in the study. Twenty-one turned out to be positive for antigliadin antibodies, and in 13 jejunal histology was consistent with celiac disease. In the remaining 8, the morphometric evaluation of jejunal biopsy specimens showed a mean surface to volume ratio that, although in the normal range, was significantly lower than that of other 10 relatives negative for antigliadin antibodies and 16 biopsied controls. It was concluded that antigliadin antibody testing is a valuable method for the screening of celiac disease among family members and that relatives with genetically predisposed gliadin sensitivity, without gross histological lesions but with minor morphometric abnormalities of the jejunal mucosa, may be regarded as subjects with latent celiac disease. PMID- 1426869 TI - Induction of cytochrome P450IA genes (CYP1A) by omeprazole in the human alimentary tract. AB - Cytochrome P450 enzymes are capable of converting procarcinogens into either active mutagens or inactive metabolites. Because the distribution of these enzymes may be important for tissue susceptibility to procarcinogens, the expression and induction of CYP1A genes in the human alimentary tract were investigated. Endoscopic biopsy specimens were obtained from buccal mucosa, esophagus, gastric body, antrum, duodenum, and colon of 6 healthy volunteers before and 1 week after taking 20 mg of omeprazole daily. Tissue specimens were analyzed for the presence of CYP1A1 and 1A2 transcripts using hybridization methods and the polymerase chain reaction. P450-dependent enzymatic activity was assessed by deethylation of ethoxyresorufin. CYP1A1 messenger RNA (mRNA) and ethoxyresorufin activity were present constitutively in the duodenum of each volunteer. Omeprazole (20 mg/day for 1 week) induced CYP1A1 mRNA and enzymatic activity in 5 of 6 volunteers. The one individual who did not initially respond had a marked increase in both mRNA and enzymatic activity after receiving 60 mg of omeprazole daily for 1 week. After treatment with omeprazole, two individuals had low levels of CYP1A1 mRNA in several other alimentary tissues as well as low levels of CYP1A2 mRNA in the duodenum. The expression and induction by a pharmaceutical agent of CYP1A genes may have implications for intestinal metabolism of ingested xenobiotics including procarcinogens. PMID- 1426871 TI - Manometry can predict feeding readiness in preterm infants. AB - To assess the usefulness of duodenojejunal manometry in predicting when neonates will tolerate enteral feeding, small intestinal manometry was performed in 48 preterm infants. Characteristics of motor activity during fasting and feeding differed in 40 infants who were identified to be tolerant and 8 who were intolerant of feeding. Among infants who were feeding intolerant, motor quiescence was less pronounced and clustered motor activity more prominent than it was in infants who were able to tolerate feedings (P < 0.005). Those infants who tolerated feedings changed their pattern of motor activity in response to feeding (P < 0.01), and infants who did not tolerate feedings had no "fed response." Infants who were initially feeding intolerant became tolerant of feedings coincident with the appearance of motor activity that was similar to that of infants who were initially tolerant to food. The sensitivity of manometry to predict feeding intolerance was 1.0, and its specificity was 0.13. PMID- 1426872 TI - Rabbit gut permeability in response to histamine chloramines and chemotactic peptide. AB - Granulocyte-derived chlorinated amines and bacterial formyl peptides are thought to enhance epithelial permeability. In the current study, gut permeability to [51Cr]ethylenediaminetetraacetic acid (EDTA) was monitored in response to luminal formyl-methionyl-leucyl-phenylalanine (fMLP) and histamine monochloramine and dichloramine. Responses were determined in rabbits during states of basal and elevated permeability. Luminal fMLP had minimal effects of gut permeability in control and injured states. Histamine monochloramine or dichloramine enhanced epithelial permeability under basal conditions; this effect was exaggerated by a pre-existing injury. Both histamine monochloramine and dichloramine retained full histamine agonist properties, and a combination of antioxidant and antihistamine therapy was required to block this increase in gut permeability. Whereas histamine chloramines caused a dose-dependent cytotoxicity in rat-cultured enterocytes, marked histological changes to the mucosa were not evident, nor were mucosal glutathione levels depleted. As histamine chloramines retain the histaminergic and oxidizing potential of their precursors, they represent a unique form of inflammatory mediator, although their highly reactive nature precludes in vivo confirmation of their formation. PMID- 1426873 TI - Biomechanical wall properties and collagen content in the partially obstructed opossum esophagus. AB - A specially designed probe was used to investigate biomechanical wall properties of the esophagus in opossums with distal esophageal banding. A balloon was stepwise inflated and deflated 6 cm above the lower esophageal sphincter before the banding and at 2 weeks postoperatively. After animals were killed, collagen content of the esophageal wall was determined. Preoperatively, cross-sectional area and wall tension at maximal inflation of the balloon, compliance, and hysteresis were 108.04 +/- 7.23 mm2, 5.8 +/- 0.3 cm H2O/m, 0.664 +/- 0.081 mm2/cm H2O, and 101.14 +/- 18.89 mm2, respectively. Postoperatively, the parameters increased to 357.45 +/- 54.22 mm2 (P < 0.001), 10.5 +/- 1.4 cm H2O/m (P < 0.001), 2.402 +/- 0.420 mm2/cm H2O (P < 0.001), and 225.86 +/- 44.56 mm2 (P < 0.05), respectively. The collagen content was 0.065 +/- 0.004 and 0.104 +/- 0.009 mg/mg dry defatted weight in the mid and distal normal esophagus, respectively, compared with 0.110 +/- 0.012 and 0.121 +/- 0.012 mg/mg in the banded group (P < 0.05 in the middle part). A positive correlation was shown between the maximal cross-sectional area and the collagen content in the mid-esophagus (P < 0.05). In conclusion, biomechanical wall properties were altered significantly, indicating dilatation and decreased ability of the esophageal wall to resist intraluminal pressure. PMID- 1426874 TI - Blood group-related antigen expression in normal and metaplastic human upper gastrointestinal mucosa. AB - Lewis antigen expression in upper gastrointestinal epithelium was studied using four monoclonal antibodies to determine the relationship between aberrant differentiation and antigen expression. Specific patterns of type 1 and type 2 Lewis blood group antigen expression were found in the surface and glands of the esophagus, gastric fundus, and duodenum. In biopsy specimens of Barrett's esophagus, gastric fundic-type columnar metaplasia expressed Lewis antigens indistinguishable from those in the normal stomach. In Barrett's junctional and specialized columnar metaplasia, Lewis a antigen was aberrantly expressed on the surface in secretors and in the glands independent of secretor state. Lewis x reactivity was markedly diminished in the glands of Barrett's junctional and specialized columnar epithelium irrespective of secretor state. There was no significant aberrancy observed in the expression of Lewis b and y antigens. The observed aberrant expression of Lewis antigens may be caused by an altered differentiation program in Barrett's metaplastic epithelium and may define a role for these glycoconjugates in the process of metaplasia and carcinogenesis in Barrett's epithelium. PMID- 1426875 TI - Failure of rectal ornithine decarboxylase to identify adenomatous polyp status. AB - Rectal mucosal ornithine decarboxylase (ODC) activity has been reported to distinguish between patients with and without adenomatous polyps (AP). In the present investigation, ODC activity has been measured in 28 patients with AP and 34 patients without AP. To assess the intraindividual variation in ODC activity, repeat biopsies were performed on 11 patients. In addition, the effect of postbiopsy sample handling was investigated by storage of samples on either dry or wet ice during transport to the laboratory. The mean rectal mucosal ODC activity in patients with AP was 196.0 +/- 195.5, whereas that in AP negative patients was 182.2 +/- 320.5. The rectal mucosal ODC activity in patients with colorectal cancer was 388.2 +/- 581. Repeat samples in individuals were generally within the same range as the original samples. The method of sample transport did not significantly affect the level of ODC measured in a particular biopsy. Because of high variability in rectal mucosal ODC activity within the population, there was wide overlap in ODC values between those patients with and without AP in an unselected general population. Thus, the measurement of flat rectal mucosal ODC activity is not a good predictor of the presence or absence of AP. Additional studies of the factors affecting mucosal ODC activity are necessary before the potential clinical utility of the method can be realized in the general population. PMID- 1426876 TI - Effect of sorbin on duodenal absorption of water and electrolytes in the rat. AB - Sorbin is a newly isolated intestinal peptide that has been purified because of its ability to induce water absorption. The effects that sorbin and some synthetic peptides corresponding to its C-terminal sequence have on duodenal absorption of water, chloride, and sodium were studied in comparison with the effects of vasoactive intestinal peptide (VIP), [D-Ala,Met]-enkephalinamide (DAMA), and angiotensin II. The technique of an in situ ligated duodenal loop in the rat was used for all peptides. Under the experimental conditions used, a low basal secretion of water, chloride, and sodium was obtained; VIP induced an increase of the secretion, whereas DAMA induced an absorption, both in the nanomolar dose range. Angiotensin II and sorbin induced an absorption in the picomolar dose range. The most effective doses of sorbin peptides but not of angiotensin induced the lowest final concentrations of Na+ and Cl- obtainable without inducing secondary water secretion. All synthetic peptides containing the C-terminal heptapeptide of sorbin were active in the picomolar dose range. Contrary to angiotensin, they had no effect on blood pressure. PMID- 1426877 TI - Alteration of the upper esophageal sphincter belch reflex in patients with achalasia. AB - Some patients with achalasia have been reported to develop airway obstruction from a massively air-distended esophagus, which may represent an abnormality in the upper esophageal sphincter belch reflex. When questioned carefully, 95% of our achalasia patients reported difficulty with belching. The upper esophageal belch reflex in 23 consecutive achalasia patients and 12 healthy controls was studied using an upper esophageal sphincter sleeve manometry catheter and rapid injection of 20-50 mL of air into the midesophagus. Compared with normal subjects, achalasia patients were significantly less likely to have an esophageal belch for all volumes tested and were more likely to have an increase rather than a decrease in upper esophageal sphincter pressure in response to air injection. This study systematically documents that many achalasia patients have an alteration in the upper esophageal sphincter belch reflex that may be a contributory mechanism for some of the chest and upper airway symptoms reported by some patients during acute esophageal distension. PMID- 1426878 TI - Chronic active gastritis due to Helicobacter pylori in immunized gnotobiotic piglets. AB - In gnotobiotic piglets, parenteral vaccination with formalin-killed Helicobacter pylori and oral vaccination with live bacteria induced H. pylori-specific serum immunoglobulins G, M, and A. Vaccination reduced but did not prevent infection by subsequent challenge with viable H. pylori. Oral vaccination with killed bacteria was less effective in inducing serum antibody and had no effect on bacterial colonization. Immunization status influenced the histologic response of piglets to challenge by H. pylori. Lymphoplasmacytic gastritis was more severe in parenterally vaccinated piglets than in the other groups. In addition, neutrophilic infiltrates and neutrophilic gland abscesses in the gastric mucosa were present in 5 of 7 parenterally immunized piglets, none of the orally immunized piglets, and only 1 of 8 infected nonimmune control piglets. Furthermore, there was a positive correlation between immunoglobulin G, M, and A titer at challenge and severity of both neutrophilic and lymphocytic inflammation. These results suggest that although vaccination does not prevent infection by H. pylori, infection of an immune host leads to increased severity and activity of gastritis. PMID- 1426879 TI - Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. AB - Immunoregulatory properties of cytokines may mediate disordered inflammatory events in ulcerative colitis (UC) and Crohn's disease (CD). In the present study, profiles of cytokines produced by activated macrophages were studied in colonic tissue from 43 patients with and without inflammatory bowel disease (IBD). Cytokine messenger RNA (mRNA) extracted from mucosal biopsy specimens was studied using polymerase chain reaction assay techniques. A greater percentage of active UC samples had detectable levels of mRNA for interleukins (IL) 1, 6, and 8 and gro than samples in inactive UC and noninflammatory controls. These cytokines were comparable in active UC and inflammatory controls. Expression of gro mRNA in active UC tissue was significantly higher than in active CD. Tumor necrosis factor was detected in only 7 of 43 samples with no difference between groups. Active and inactive CD did not differ in percentage of cytokine mRNA expression. IL-1 receptor antagonist (IL-1ra) was detected in more inflammatory controls than in CD and was expressed in fewer IBD patients than IL-1. Expression of proinflammatory cytokines in grossly inactive CD and possible defective production of IL-1ra may explain disease reactivation and chronicity. PMID- 1426880 TI - Effect of gastrin receptor blockade on endocrine cells in rats during achlorhydria. AB - Hyperplasia of the oxyntic enterochromaffinlike cells in response to long-lasting blockade of acid secretion is closely related to hypergastrinemia. In the present study, the effect of a specific gastrin receptor antagonist on proton pump inhibitor-induced changes on serum gastrin levels, mucosal height, as well as gastrin- and enterochromaffin-like cells was investigated in rats. The proton pump inhibitor BY 308 or the vehicle methylcellulose [Methocel (controls)] was administered for 2 weeks in the presence and absence of the gastrin receptor antagonist PD 136450 (CAM 1189). BY 308 significantly increased serum gastrin levels, gastrin cell density, and antral gastrin concentration. Concomitant application of PD 136450 did not alter this response. In the oxyntic stomach, mucosal height, enterochromaffinlike cell density, labeling index of enterochromaffinlike cells, and histamine concentration were elevated after treatment with BY 308. These increases were almost completely abolished by PD 136450. Even in normogastrinemic control rats, PD 136450 significantly decreased mucosal height of the oxyntic part of the stomach and the labeling index of enterochromaffinlike cells. The results show that (a) trophic effects of drug induced achlorhydria are mediated by gastrin; (b) even in control rats (normogastrinemic), gastrin is a trophic factor for the oxyntic mucosa; and (c) antral gastrin cell hyperplasia in states of chronic achlorhydria is not mediated by gastrin itself. PMID- 1426881 TI - DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. AB - The objective of the present study was to determine whether abnormal epithelial DNA content (aneuploidy) in colonic biopsy specimens from ulcerative colitis (UC) patients correlated with and predicted histological progression to dysplasia. Aneuploidy was absent in 20 low-cancer risk patients. In 81 high-cancer risk patients aneuploidy correlated significantly with the severity of histological abnormality (negative, indefinite, dysplasia, or cancer). Statistically our data suggest that many more biopsy specimens than are usually taken are needed to detect focal dysplastic lesions. Prospective study of 25 high risk patients without dysplasia revealed 5 with aneuploidy, all of whom progressed to dysplasia in 1-2.5 years, whereas 19 patients without aneuploidy did not progress to either aneuploidy or dysplasia within 2-9 years. Our data indicate that aneuploidy in mucosal biopsy specimens correlates with histological grade and identifies a subset of patients without dysplasia who are more likely to develop it. It was concluded that more frequent and extensive colonoscopic surveillance of this minority subset of high risk patients and less frequent surveillance in the remaining majority may reduce cost and detect more curable lesions. PMID- 1426882 TI - Serum hepatocyte growth factor levels in hepatectomized and nonhepatectomized surgical patients. AB - Serum hepatocyte growth factor levels were measured in hepatectomized and nonhepatectomized surgical patients. The levels were significantly increased and reached a maximum within 7 days after surgery in both groups, returning to preoperative levels 28 days after partial hepatectomy and 7 days after other operations. Multiple regression analysis showed that such maximal hepatocyte growth factor levels were significantly related to having liver cirrhosis and postoperative maximal serum total bilirubin and alanine aminotransferase levels and peripheral white blood cell counts in the hepatectomized group and to postoperative maximal peripheral white blood cell counts and serum C-reactive protein levels in the nonhepatectomized group. However, the levels showed no relation to the resected liver volume and increment of the remaining liver volume 28 days after partial hepatectomy. It is concluded that serum hepatocyte growth factor levels were increased after partial hepatectomy in association with hepatocellular dysfunction and necrosis and systemic inflammation. It is unlikely that the increase was related to liver regeneration. PMID- 1426883 TI - Antioxidant defenses in the bile duct-ligated rat. AB - Changes in pro-oxidant and antioxidant balance in the serum and liver were studied in an experimental model of obstructive jaundice in the rat. The results showed a decrease in plasma vitamin E concentration (P < 0.01) and a threefold reduction in liver vitamin E concentration (P < 0.001). There was also a threefold reduction in levels of the liver enzymes glutathione peroxidase (P < 0.01) and glutathione transferase (P < 0.001), together with a six-fold reduction in catalase activity (P < 0.001). The serum selenium level decreased by 35% in the jaundiced rats (P < 0.05). The total liver glutathione level decreased to half the control value (P < 0.01). The malonyldialdehyde level, the measure of lipid peroxidation used in this study, doubled (P < 0.01). The results suggest a shift in the pro-oxidant/antioxidant balance in favor of lipid peroxidation. The possible etiology of this change and its relationship to human cholestasis are discussed. PMID- 1426884 TI - Survival and prognostic indicators in hepatitis B surface antigen-positive cirrhosis of the liver. AB - To evaluate indications for new therapies such as liver transplantation and antiviral therapy, survival of histologically proven hepatitis B surface antigen (HBsAg)-positive cirrhosis of the liver was assessed in a cohort of 98 patients followed up for a mean of 4.3 years. The overall survival probability was 92% at 1 year, 79% at 3 years, and 71% at 5 years. Variables significantly associated with the duration of survival were age, serum aspartate aminotransferase levels, presence of esophageal varices, and all five components of the Child-Pugh index (bilirubin, albumin, coagulation factors, ascites, encephalopathy). Multivariate analysis showed that only age, bilirubin, and ascites were independently related to survival. Survival of patients with decompensated cirrhosis (determined by the presence of ascites, jaundice, encephalopathy, and/or a history of variceal bleeding) and those with compensated cirrhosis at 5 years was 14% and 84%, respectively. For patients with compensated liver cirrhosis, hepatitis B e antigen (HBeAg) positivity was also a prognostic factor with a 5-year survival of 72% for HBeAg-positive cirrhosis and 97% for HBeAg-negative cirrhosis; the risk of death was decreased by a factor of 2.2 when HBeAg seroconversion occurred during follow-up. It is concluded that liver transplantation should be considered for patients with decompensated HBsAg-positive liver cirrhosis and antiviral therapy for patients with HBeAg-positive compensated cirrhosis. PMID- 1426885 TI - Prognostic factors in sterile pancreatic necrosis. AB - Although the overall mortality in sterile pancreatic necrosis is low, patients who experience systemic complications may have a higher mortality. To study the impact of systemic complications and other factors on survival, possible prognostic factors were evaluated among 26 patients who experienced at least one systemic complication. Mortality was 38%. Factors that correlated with a fatal outcome were high Ranson's scores during the first 48 hours (P = 0.01), high APACHE-II scores at admission (P = 0.04) and at 48 hours (P = 0.03), shock (P < 0.001), renal insufficiency (P < 0.05), multiple systemic complications (P < 0.001), and high body mass index (P = 0.01). Most systemic complications occurred during the first 2 weeks of illness. Logistic regression analysis showed that shock was the best predictor of a fatal outcome. Patients with favorable prognostic factors survived whether treated medically or surgically, whereas those with unfavorable factors had a fatal outcome whether treated medically or surgically. It is concluded that patients with severe sterile necrosis have a high mortality rate and that shock and other prognostic factors identify which patients are most likely to have a fatal outcome. PMID- 1426886 TI - Hepatic cholesterol metabolism in estrogen-treated men. AB - Operative liver biopsies were obtained from two male patients who developed gallstone disease during estrogen treatment of metastatic prostatic carcinoma. The heparin-sensitive binding of 125I-low-density lipoprotein (LDL) to liver homogenates (reflecting the expression of the LDL receptor) was determined, together with the activities of the rate-limiting enzymes in cholesterol synthesis [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase], bile acid production (cholesterol 7 alpha-hydroxylase), and cholesterol esterification (acyl CoA:cholesterol acyl transferase). The results were related to data available in 18 patients (5 male, 13 female) who underwent cholecystectomy because of gallstone disease. The hepatic 125I-LDL-binding activity was increased threefold compared with five controls, and the activity of HMG-CoA reductase was increased twofold. There was no major difference in the activities of cholesterol 7 alpha-hydroxylase or acyl CoA:cholesterol acyl transferase. The concentration of free and total cholesterol in liver microsomes was approximately 30% lower in the estrogen-treated men than in 11 controls. The results indicate that estrogen at pharmacological doses stimulates hepatic LDL-receptor expression and HMG-CoA reductase activity in men. The increased LDL-receptor expression could in part explain the enhanced plasma clearance of injected 125I-LDL and hence the reduction in plasma LDL cholesterol previously shown to occur in estrogen-treated men. PMID- 1426887 TI - Menetrier's disease associated with formula protein allergy and small intestinal injury in an infant. AB - Menetrier's disease in infancy is extremely rare, and its natural course has not been studied in detail. The present case report describes an infant whose initial diagnosis was formula protein allergy and who developed gastric outlet obstruction by 3 months of age. The diagnosis of Menetrier's disease was suggested by characteristic radiological, pathological, and functional abnormalities of the stomach. Small intestinal partial villous atrophy, malabsorption, and protein loss from both the stomach and the intestine were documented. Cytomegalovirus infection was excluded. There was no evidence for an immune deficiency. The described features and an unrelenting course suggest that infantile Menetrier's disease may be an entity distinct from the childhood and adult forms. PMID- 1426888 TI - The beneficent belch. PMID- 1426889 TI - Hepatitis B-related end-stage liver disease. PMID- 1426890 TI - Eradication of Helicobacter pylori reduces gastric and duodenal ulcer recurrence. PMID- 1426891 TI - What is intensive therapy for gastroesophageal reflux? PMID- 1426892 TI - Can esophagus be blamed for noncardiac chest pain? PMID- 1426893 TI - Interferon alfa in acute posttransfusion hepatitis C: a randomized, controlled trial. PMID- 1426894 TI - Anti-neutrophil cytoplasmic autoantibodies in relatives of patients with ulcerative colitis. PMID- 1426895 TI - Oral 4-aminosalicylic acid therapy in ulcerative colitis. PMID- 1426896 TI - Bile salt-induced biliary excretion of iron in iron-loaded rats. PMID- 1426897 TI - Indian childhood cirrhosis--need for uniform criteria. PMID- 1426898 TI - L-carnitine for treatment of distal ulcerative colitis. PMID- 1426899 TI - Renal insensitivity to atrial natriuretic peptide in patients with cirrhosis and ascites. PMID- 1426901 TI - [Blood protein-volume indicators in massive plasmapheresis]. AB - Hyperproteinemia values were studied before and after plasmapheresis in 32 rheumatoid arthritis patients with no manifest circulatory disorders. Mathematical patterns enabling prediction of changes in protein concentration depending on the volume of removed plasma and the type of substitution have been proposed for 3 alternative regimens of the procedure (removal of 0.5 or 1.0 volume of the circulating plasma, and substitution for rheopolyglucin or albumin). The data of independent "examining" sampling (15 patients) have proved adequacy of the linear regression patterns. PMID- 1426900 TI - [Suppressive effect of circulating immune complexes on cytotoxicity of blood lymphocytes in patients with chronic myeloid leukemia]. AB - Concentration of circulating immune complexes (CIC) and cytotoxicity (natural and antibody-dependent) of blood lymphocytes were studied in 52 patients at the developed stage of chronic myeloid leukemia (CML). Elevation of CIC level and reduction of cytotoxicity detectable in all CML patients were most manifest in those with high tumor mass and during exacerbation of the leukemia process. A conclusion has been made that CIC are suppressors of natural and antibody dependent cytotoxicity of blood lymphocytes in CML patients. PMID- 1426902 TI - [Preparation of universal anti-rhesus sera using soluble synthetic group A and B substances]. AB - Isohemagglutinins alpha and beta were neutralized by soluble synthetic group A and B substances in group ++anti-rhesus sera. The investigations conducted have shown that water-soluble polymers A and B are efficient agents for the preparation of universal ++anti-rhesus sera. The neutralizing properties of synthetic and natural group A and B substances were comparatively studied. PMID- 1426903 TI - [Refractory effect and alloimmunization after transfusion of thrombocytes]. AB - The authors discuss possible ways for prevention of alloimmunization with HLA antigen in acute leukemia patients after platelet transfusions. Prevention or delay of HLA-alloimmunization is possible when platelets of single random donor are used instead of pooled random donor platelets for transfusions. The effect of leucocyte removal from platelet concentrates and ultraviolet irradiation of platelet concentrates under conditions of blood bank on alloimmunization and refractoriness incidence has been considered. PMID- 1426904 TI - [The role of plasma fibronectin in the pathogenesis of post- aggressive conditions]. AB - The interrelations of changes in plasma fibronectin (FN) level, hemostatic parameters and RES function were studied in the time course of traumatic or burn disease. A combination of interdependent disorders in the systems studied reflecting features of varying periods of extreme states was established in rat experiments. The analysis of the data obtained has suggested that FN is involved in the pathologic process and participates in the pathogenesis of shock and its complications by interacting with hemostasis and RES as a mediator thus playing an important role in maintaining the level of nonspecific body resistance. PMID- 1426905 TI - [Current development of the problem of "artificial blood"]. PMID- 1426907 TI - [Use of a new protein-salt solution protesalin in the treatment of experimental hemorrhagic shock]. PMID- 1426906 TI - [Hemolytic anemia, caused by "warm" antibodies, in negative direct antiglobulin test]. PMID- 1426908 TI - [Concept of development of the research on hemoblastoses and depression of hematopoiesis within the national program "Control of the most prevalent diseases"]. PMID- 1426909 TI - [Myelodysplastic syndromes in children]. PMID- 1426910 TI - [Stomatologic aid to patients with hereditary coagulopathies under ambulatory conditions in the hemophilia center]. AB - Simple and available for wide clinical practice methods of treatment and prevention of complicated forms of dental caries in patients with hemophilia and Willebrand's disease have been presented, as well as effective methods for prevention of hemorrhage from the small cavity after a tooth removal in these patients under conditions of hematological centres. PMID- 1426911 TI - [Transferrin iron-binding capacity in hypersideremia]. AB - Three methods for evaluation of serum iron-binding capacity have been described: biochemical, immunological based on transferrin assay, and biophysical based on electron-paramagnetic resonance (EPR) spectroscopy of transferrin. Interrelation has been shown between transferrin and general serum iron-binding capacity. Basing on the data presented it is suggested that in secondary hemochromatosis plasma contains an iron pool that is not specifically bound with transferrin, while in primary hemochromatosis such pool was not detected. PMID- 1426912 TI - [Influence of mast cells on the regulatory mechanisms of hemopoietic bone marrow in inflammation]. AB - Acute infectious peritonitis simulated in mice was used to show that previous osmotic deterioration of the abdominal mast cell population significantly influenced the function of hemopoiesis-inducing microenvironment (HIM). The earlier production of the colony-stimulating and erythropoietic activities by the non-adhesive myelokaryocytes and the decreased production of these activities by the adhesive cells have been established. The results obtained evidence that mast cells modulate HIM mediating their influence on hemopoiesis under natural conditions of inflammation. PMID- 1426913 TI - [Erythrocytic ferritin in pregnant women and infants in the first year of life]. AB - Erythrocytic ferritin levels were followed up in pregnant women with reference to its course, in newborns, and in infants during the first year of life. It is shown that the level of erythrocytic ferritin remains high enough in women with complicated pregnancy attended by a sharp reduction of iron reserves. No clear dependence of erythrocytic ferritin concentration on the character of the antenatal period course was observed in infants. The highest values of erythrocytic ferritin parameters were recorded by the first month and they decreased constantly by the first year of life. PMID- 1426914 TI - [Combined evaluation of iron reserves in women]. AB - Peripheral blood hemoglobin levels, serum iron, general serum iron-binding capacity, transferrin saturation with iron, transferrin, serum ferritin and erythrocytic ferritin were studied in 101 clinically normal women. Apparent and latent iron deficiency was rather frequently detected among them. Information on transferrin saturation with iron, erythrocytic ferritins and, particularly, serum ferritin, was most valuable in the estimation of iron deficiency. The combined evaluation of erythrocytic and serum ferritins has permitted the authors to distinguish 5 variants of iron reserves in the body and to avoid discrepancy arising in their individual estimations. PMID- 1426915 TI - [Intravascular autorosette-formation in hemolytic anemia]. AB - It has been established that monocyte and neutrophil autorosette-formation resultant in exocytic lysis of erythrocytes--constituents of autorosettes--takes a low-intensive course in the blood of children with chronic non-hematologic diseases. This process is significantly activated in hereditary microspherocytic and elliptocytic anemias. It has been suggested that autorosette-formation culminating in exocytic lysis of erythrocytes is a mechanism of eliminating pathological, damaged and old erythrocytes from the blood, both under physiological conditions and in varying diseases. PMID- 1426916 TI - [Iron metabolism in anemia patients with no deficiency of iron reserves]. AB - Iron metabolism was studied in anemia patients with no iron deficiency. The data obtained have suggested that iron transport to blood-synthesizing cells i disturbed in such patients with normal iron reserves. Basing on the study of iron metabolism and red blood parameters in the patients after the treatment by hypoxic hypoxia it is shown that this method combined with iron therapy can be successfully used for the treatment of this form of iron deficiency anemia. PMID- 1426917 TI - [Effect of artificial electromagnetic fields on living organisms]. PMID- 1426918 TI - [Dynamics of volemic parameters in patients with pyo-destructive pulmonary and pleural diseases in various types of substitution of removed plasma in the process of plasmapheresis]. PMID- 1426919 TI - [Two-quantum photodynamic inactivation of viruses in blood preparations]. PMID- 1426920 TI - [Preservation of platelet concentrates isolated from platelet-enriched donor plasma]. PMID- 1426921 TI - [Protein impurities in purified hemoglobin solutions]. PMID- 1426922 TI - [Extraction of excessive malonic dialdehyde and cholesterol from erythrocytes using natural latex]. PMID- 1426923 TI - [Diagnostic value of serum iron metabolism parameters in patients with malignant and reactive histiocytosis]. AB - Difficulties in the morphological diagnosis of the diseases due to proliferation of mononuclear phagocyte system (MPS) cells have stimulated the search for additional differential-diagnostic criteria. The investigations were conducted in 10 malignant histiocytosis, 16 histiocytosis-X, and 34 reactive histiocytosis patients. The assay of serum ferritin was shown to have high informative value for clinical practice. The presence of extremely high hyperferritinemia in patients with morphologically verified histiocytic proliferations has evidenced a malignant character of the process. PMID- 1426924 TI - [Clinical criteria for evaluation of hemophilia severity in expert estimation of patient's working capacity]. AB - Data are presented on the evaluation of hemophilia severity during expert estimation of the patient's working capacity according to the information of the Republican Centre. The authors have developed the most optimal classification for the evaluation of the disease severity; the influence of hemorrhagic symptoms and concomitant diseases on hemophilia course and prognosis has been considered. PMID- 1426925 TI - Actions of two novel prostaglandin analogs, SC-29169 and SC-31391, on guinea pig and human isolated urinary bladder. AB - 1. We examined the effects of two novel PGE1 analogs, SC-29169 and SC-31391, on bladder muscle isolated preparations from guinea pig and man, in comparison with some naturally-occurring prostanoids and misoprostol. 2. In the guinea pig detrusor muscle, both prostaglandin analogs enhanced twitch responses elicited by field stimulation in the following order of potency: SC-31391 greater than SC 29169 greater than PGF2 alpha greater than or equal to PGE2, while a well-defined contractile effect was elicited only by SC-31391. 3. In the human detrusor muscle, nerve-mediated responses were not modified by prostaglandin analogs, as well as by PGF2 alpha or PGE2, while a contractile effect was observed with the same compounds: PGF2 alpha = SC-31391 greater than SC-29169 = PGE2 = PGE1. 4. The selective EP1-agonist, misoprostol did not induce any effect, in both guinea pig and human bladder. 5. These data suggest that the effect of prostaglandins in the bladder muscle differs according to the animal species and that, in the human detrusor muscle, SC-31391 and SC-29169 probably stimulate FP receptors. PMID- 1426926 TI - Mast cells mediators evoke contractility and potentiate each other in mouse uterine horns. AB - 1. The ability of prostaglandin F2 alpha (PGF2 alpha), histamine and serotonin to induce and/or potentiate contractions in mouse uterine horns was studied in an attempt to analyze whether uterine mast cells degranulation could favor contractions during labor. 2. PGF2 alpha was the most potent of the three compounds (EC50 = 0.7 microM), being followed by serotonin (EC50 = 1.2 microM) and histamine. Between 10 and 100 microM histamine only evoked weak contractions, not higher than 50% of maximal amplitude of contractions. 3. Serotonin (0.1 microM) potentiated the contractile effect of both histamine and PGF2 alpha when added simultaneously with the corresponding compound to the isolated organ bath. Also, histamine at threshold contractile concentration (3 microM) was able to potentiate the contractile effect of both serotonin and PGF2 alpha. 4. The potentiating effect of PGF2 alpha on both histamine and serotonin evoked contractions was recorded after treating the preparation with 10 microM of the compound for at least 10 min before the corresponding concentration-effect curves were performed. 5. It is postulated that the simultaneous presence of these mast cells mediators in myometrium could be an important stimulus for both to trigger and/or to maintain contractions during labor. PMID- 1426927 TI - The responses to phorbol esters which stimulated protein kinase C in canine Purkinje fibers. AB - 1. The effects of phorbol esters on canine Purkinje fibers were examined using conventional microelectrode techniques. 2. 12-O-Tetradecanoylphorbol-13-acetate (TPA) and 4-beta-phorbol-12,13-dibutyrate (PDB), which are specific activators of protein kinase C (PKC), decreased the action potential amplitude and the maximum rate of depolarization (Vmax) at 3 x 10(-7) M or higher. These phorbol esters had little effect on the resting potential. 3. PDB (1-3 x 10(-7) M) also reduced the contractile force, accompanied with initial increase (in 5 out of 8 experiments), whereas TPA did not decrease it to any significant extent. 4. An inactive analog of phorbol esters, 4-alpha-phorbol-12,13-didecanoate (PDD), decreased the action potential amplitude and Vmax, and slightly increased the action potential duration. However, PDD failed to produce any inotropic effect. 5. Post-rest potentiation of the contractile force after a rest from stimulation for 30 sec was inhibited in the presence of 3-10 x 10(-7) M TPA or 3 x 10(-7) M PDB. 6. Isoproterenol 10(-7) M augmented the action of PDB 3 x 10(-7) M. 7. These results suggest that activation of PKC may modulate myocardial Ca2+ homeostasis and influence the excitation-contraction process. PMID- 1426928 TI - Repeated treatment with quinolones potentiates the seizures induced by aminophylline in genetically epilepsy-prone rats. AB - 1. The effects of a chronic treatment with several quinolone derivatives on on the aminophylline-induced convulsions in the genetically epilepsy-prone rat have been investigated. 2. Two series of experiments have been performed: in the first one animals received the quinolone twice a day for 5 days, then were given aminophylline (80-140 mg.kg-1, i.p.); in the second series of experiments the rats were treated once a day with the quinolone plus 120 mg.kg-1 of aminophylline for 5 days. The changes induced by both treatment protocols on electrocortical activity and on the occurrance of seizures have been evaluated. 3. Enoxacin reduced the dose of aminophylline necessary for the induction of seizures in a higher degree with respect to the other quinolone derivatives. The derivatives which showed minor proconvulsant properties were ofloxacin, ciprofloxacin and cinoxacin. The potentiation of seizures induced by quinolones appeared a dose dependent phenomenon which was more evident when high doses of quinolones were used. 4. The chronic treatment carried out daily with quinolones and aminophylline suggests that additive neurotoxic effects of both classes of drugs may contribute to the increase of severity of seizure scores. 5. The possible role of GABA-benzodiazepine, excitatory amino acid, purinergic mechanisms as well as the role of pharmacokynetic factors are discussed. PMID- 1426929 TI - Pharmacological characterization of ATP receptors mediating vasodilation on isolated rabbit aorta. AB - 1. The effects of adenosine 5'-triphosphate (ATP), 2-methyl-thio-ATP and adenosine on rabbit aorta were examined in isolated preparations precontracted by noradrenaline, both in vessels where the endothelium was present and mechanically removed. 2. In the presence of endothelium, ATP (30 microM-3 mM) induced a relaxation that was reduced by removal of the endothelium. 3. The maximum endothelium-dependent relaxation of ATP was twice the maximum endothelial activity of the potent agonist at P2y-purinoceptors, 2-methyl-thio-ATP. 4. Adenosine which acts on P1 purinoceptors, induced a relaxant effect at 1 mM concentration, both in the vessels with and without endothelium. 5. It is concluded that relaxation by ATP is induced both via the endothelial P2y purinoceptor and via a "nucleotide" receptor that is located on endothelium and on smooth muscle of rabbit aorta. PMID- 1426930 TI - Effects of S14001 on adrenergic neuroeffector interaction in isolated canine saphenous veins. AB - 1. The effects of (S) fluoro-6 (morpholinyl-2 methoxy)-8-tetrahydro-1,2,3,4 quinoleine (S14001) on adrenergic neurotransmission in isolated canine saphenous veins were investigated in experiments which measured the accumulation, overflow and metabolism of 3H-norepinephrine. 2. S14001 inhibited the accumulation of total tritium (3H-norepinephrine and 3H-metabolites of norepinephrine) in a concentration-dependent manner. 3. Under basal conditions, S14001 increased tension and basal effiux of total tritium; the latter consisted predominantly of 3H-DOPEG. The increases in these parameters were not inhibited by desmethylimipramine (DMI). 4. During electrical stimulation, S14001 increased the contraction and overflow of total tritium; the latter consisted predominantly of 3H-DOPEG. The increases in these parameters were inhibited by DMI. 5. These experiments suggest that S14001 has dual effects on adrenergic neurotransmission in the canine saphenous vein: (a) an inhibitory action on the neuronal accumulation; and (b) a pharmacological displacement of the transmitter from adrenergic nerve terminals. PMID- 1426931 TI - Comparison of acute effects of mitoxantrone and doxorubicin in guinea-pig atria. AB - 1. The acute effects of doxorubicin (DOX) and mitoxantrone (MTX) on basal rate and on positive chronotropic activity induced by 1-noradrenaline (1-NA) were investigated in isolated guinea-pig atria. 2. DOX (10(-5)-10(-4)M) progressively depressed atrial rate after a short latency period. Only 10(-4) M MTX reduced the spontaneous frequency after 120 and 180 min incubation. This effect was significantly lower to that elicited by DOX (10(-4)M). 3. Atropine (1.5 x 10(-6) M) and reserpine pretreatment did not affect the negative chronotropic action induced by DOX or MTX. 4. DOX (10(-5)-10(-4) M) produced a significant reduction of the maximal chronotropic response (Emax) to 1-noradrenaline (1-NA) after 60, 120 and 180 min of exposure. 5. MTX (10(-5)-10(-4) M) after 60 and 120 min incubation induced a beta-adrenergic, concentration- and time-dependent, competitive blocking effect. After 180 min of exposure, MTX (10(-4) M) reduced the Emax to 1-NA which was of less magnitude to that produced by DOX (10(-4) M). 6. Although both DOX and MTX depressed spontaneous and 1-NA induced chronotropic activity, MTX effects were of a slower onset and development compared to those exerted by DOX. PMID- 1426932 TI - Alterations of G protein function in cardiac tissues from streptozotocin-induced chronic diabetic rats. AB - 1. This study was performed to investigate G protein function in cardiac tissues from chronic diabetic rats by using pertussis toxin (PTX) and cholera toxin (CTX) as probes for G(i) and Gs proteins, respectively. 2. In the 10-week control group, i.v. injection of PTX significantly elevated the basal heart rate without having any effect on the chronotropic response of right atria to increasing concentrations of isoproterenol (ISO). In the 10-week diabetic rats, PTX treatment had no effect on the basal heart rate or on the response of right atria to ISO. In the 6-month groups, PTX did not exert any effects on basal or ISO stimulated heart rate in either control or diabetic rat. 3. The inhibitory effect of carbachol (CCH) on cardiac tension in ISO-stimulated left atria was completely abolished by i.v. injection of PTX in the 10-week groups (both control and diabetic rats). The same treatment, however, only slightly reduced the effect of CCH on left atria contraction in rats from 6-month groups. 4. In both control and diabetic rats in the 10-week groups, incubation with CTX caused a significant increase in heart rate in right atria, and in developed cardiac tension in left atria preparations. The magnitude of the increase was the same in both control and diabetic rats. 5. Studies carried out using ADP-ribosylation technique indicated that the amount of G(i) protein was not changed in the ventricular muscle of the 10-week diabetic rat. Labelling of Gs protein could not be detected in either control or diabetic rat heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426933 TI - Effects of androgens and antiandrogens on the inotropism induced by ouabain and isoproterenol on the left atrium of the rat in vitro. AB - 1. The effect of androgens 5 beta- and 5 alpha-dihydrotestosterone (DHT, 10(-9) M), and the antiandrogens cyproterone acetate (CPA, 10(-8)-10(-6) M), chlormadinone acetate (CMA, 10(-8)-10(-6) M), medroxyprogesterone acetate (MPA, 10(-8)-10(-6) M), spironolactone (SPI, 10(-5) M), flutamide (F, 10(-5) M) and cimetidine (C, 10(-5) M), on inotropic positive effect induced by ouabain (10(-8) 10(-5) M) and isoproterenol (10(-8)-10(-6) M), on electrically stimulated left atria of rat, has been assayed. 2. Ouabain (10(-6) M) did not modify the inotropic effect of isoproterenol (10(-8)-10(-6) M). 3. The androgens 5 beta- and 5 alpha-DHT (10(-9) M) and the antiandrogens SPI (10(-6) M), F (10(-5) M) and C (10(-5) M) inhibit the inotropic effect of ouabain and isoproterenol on electrically stimulated left atria of the rat. 4. The antiandrogens CPA, MPA and CMA to 10(-7) M, inhibit the inotropic effect of ouabain. The CPA (10(-8)-10(-6) M) inhibit, in a dose-dependent way the positive inotropic effect of isoproterenol. MPA and CMA (10(-8)-10(-6) M) also inhibit the inotropic effect isoproterenol but the inhibitory effect is greater with 10(-8) M than 10(-6) M of both drugs. 5. Taken together, our results suggest that steroidal hormones could modulate the cardiac contractility through interference with Na-pump in a non digitalic site and/or with intracellular mediators in left atrium. PMID- 1426934 TI - Effects of secretagogues on intracellular free calcium and magnesium concentrations in rat pancreatic acinar cells. AB - 1. Rat pancreatic acinar cells were loaded with Fura 2 AM or Magfura AM and levels of cytosolic Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were observed. 2. Addition of acetylcholine (ACh) evoked a transient rise in [Ca2+]i. The component of the rise dependent on extracellular Ca2+ sources, but not intracellular sources, was seen to be enhanced when both ACh and 5 mM Ca2+ were present in the medium. In the presence of elevated extracellular Mg2+ (10 mM) and ACh both components of the Ca2+ transient were inhibited. 3. Both GTP gamma S and fluoroaluminate, which can directly stimulate G-proteins, evoked a transient rise in [Ca2+]i in acinar cells. These responses were inhibited in the presence of elevated Mg2+. 4. Resting [Mg2+]i was seen to be 1.36 mM +/- 0.08 (n = 29) for cells in normal medium, 1.8 mM +/- 0.08 (n = 6) in elevated Mg2+ medium and 0.93 mM +/- 0.02 (n = 5) in cells bathed and Mg(2+)-free medium. Addition of ACh led to reductions in [Mg2+]i in cells bathed in normal medium and Mg(2+)-free medium but not elevated Mg2+ medium. 5. It is concluded that levels of extracellular Mg2+ strongly influence [Mg2+]i and [Ca2+]i mobilization during ACh-evoked responses. Mg2+ does not appear to be exerting its effects by influencing receptor-agonist interactions or by competing with Ca2+ at extracellular sites of Ca2+ uptake. PMID- 1426935 TI - Effect of ATP and verapamil as cardioplegic additives in the isolated guinea pig heart. AB - 1. A comparative study on isolated guinea pig hearts was carried out to determine the effects of ATP and verapamil as cardioplegic additives. 2. The hearts were arrested by one of the plegic solutions: I, potassium 20 mmol/l; II, potassium 20 mmol/l+verapamil 1.1 mumol/l; III, potassium 20 mmol/l+ATP 10 mmol/l. After 45 min of hypothermic ischemia, the hearts were reperfused by Krebs-Henseleit buffer. 3. Postischemic percentage change of myocardial functions (heart rate, contractility, heart work) and tissue enzymes (LDH, SGOT, SGPT) were compared between the groups. 4. Although a rapid cardiac arrest could be obtained by verapamil added cardioplegia. Postischemic myocardial recovery was much better with ATP added cardioplegic solutions. PMID- 1426936 TI - Influence of ATP-sensitive potassium channel blocker on hypoxia-induced damage of isolated guinea pig heart. AB - 1. Isolated guinea pig hearts were perfused under constant flow conditions with Krebs-Henseleit buffer. Hearts were subjected to 15 min of hypoxia followed by reoxygenation in the presence and in the absence of 100 microns glyburide, an ATP sensitive potassium channel blocker. Heart rate, left ventricular pressure and lactate dehydrogenase (LDH) release were measured at 5 min intervals. 2. Small decreases in heart rate and left ventricular pressure were observed during glyburide infusion with hypoxia, however LDH release, which was used as an index of cellular damage, was dramatically elevated. 3. Neither glyburide, nor the vehicle in which it was dissolved, appeared to produce myocardial damage under normoxic conditions. 4. It is concluded that ATP-sensitive potassium channels are important in the protection of the myocardium during hypoxia in isolated guinea pig hearts perfused under constant flow conditions. PMID- 1426937 TI - Maturational gonadotropin from the African catfish, Clarias gariepinus: purification, characterization, localization, and biological activity. AB - A gonadotropic hormone of the African catfish, Clarias gariepinus, was was purified and chemically characterized. Its biological activity was tested and its localization in the gonadotropic cells of the pituitary demonstrated. An ethanolic extract of 500 pituitaries of adult male and female African catfish was subjected to ion-exchange chromatography on DE-52. The 31- to 38-kDa fraction was further purified on Sephadex G-75. On rpHPLC over an ODS 120T column two major components appeared as single bands after SDS-PAGE. From the amino acid composition and sequence analysis of these fractions, compared with those of salmon and carp GTH II-alpha and salmon GTH II-beta it was concluded that they represent catfish GTH alpha- and II-beta-subunits. The biological activity of the complete hormone (the 31- to 38-kDa fraction from the G-75 column) was tested on the production of 11 beta-hydroxyandrostenedione and 17 alpha-hydroxy-20 beta dihydroprogesterone by catfish testis in vitro. Polyclonal antibodies were raised against the purified beta-subunit. Immunocytochemical study using these showed them to bind specifically to hypophysial gonadotropic cells. To date only one form of GTH has been demonstrated in the African catfish. PMID- 1426938 TI - Chronic fasting reduces the response of the thyroid to growth hormone and TSH, and alters the growth hormone-related changes in hepatic 5'-monodeiodinase activity in rainbow trout, Oncorhynchus mykiss. AB - Chronically fasted rainbow trout (Oncorhynchus mykiss) had significantly lower plasma L-thyroxine (T4) and triiodo-L-thyronine (T3), and higher plasma growth hormone (GH) concentrations than fed animals. Fasted and fed trout were administered bovine thyrotropic hormone (bTSH), native ovine GH (oGH), or recombinant human GH (rhGH) alone, or GH in combination with bTSH to further study the effects of food deprivation on the activity of the pituitary-thyroid axis and on the control of hepatic T3 production. Although the fasted rainbow trout retained the ability to respond to bTSH challenge, the resultant elevation in plasma T4 concentration was significantly lower than that of fed animals; there was no plasma T3 response to bTSH challenge in either fed or fasted trout, except for a significant elevation in fed bTSH-injected fish and a significant depression in fed saline-injected fish sampled 2.5 hr after the injection. GH when administered alone had no significant effect on plasma T4 concentrations of either fed or fasted animals, and stimulated an increase in plasma T3 concentration and an increased hepatic T3 content only in the fed fish, despite a significant stimulation by both oGH and rhGH of in vitro hepatic 5' monodeiodinase activity (MDA) in both fed and fasted groups. bTSH appeared to suppress rhGH- and oGH-stimulated MDA in fasted groups, and rhGH-stimulated MDA in fed trout. The data suggest that chronic fasting induced a down-regulation of the response of thyroid tissue to bTSH challenge, and of the GH-stimulation of T3 production, in vivo, although in vitro hepatic MDA was elevated following GH administration to both fed and fasted rainbow trout. PMID- 1426939 TI - Light and electron microscopic immunocytochemical demonstration of synthesis, storage, and release sites of the neuropeptide calfluxin in Lymnaea stagnalis. AB - The cerebral caudodorsal cells (CDC) of the pulmonate snail Lymnaea stagnalis control egg-laying and associated behaviors. They produce various peptides derived from two precursor molecules, proCDCH-I and II, one of which is calfuxin (CaFl). CaFL is involved in the control of the activity of a female accessory sex gland, the albumen gland. At the light microscope level, using an antibody raised against synthetic CaFl, immunoreactivity was demonstrated in all CDC somata as well as in the neurohemal CDC terminals in the periphery of the cerebral commissure and in the CDC axon collaterals in the inner region of the commissure. A group of small neurons in each cerebral ganglion was also immunopositive. At the ultrastructural level, secretory granules (SG) and large electron-dense granules (LG), formed by the Golgi apparatus and thought to be involved in intracellular degradation of secretory material, were clearly immunolabeled. The density of immunolabeling of LG was 3.3 times greater than that of SG, indicating that CaFl is preferentially packed into LG. In the LG, the density of immunolabeling with anti-alpha CDCP (alpha CDCP is also a peptide derived from proCDCH-I and II) was 10 times greater than in SG, suggesting that CaFl and alpha CDCP are processed and sorted in (quantitatively) different ways. In the neurohemal terminals SG release their CaFl-immunopositive contents into the hemolymph by the process of exocytosis, whereas collaterals release such contents into the intracellular space of the intercerebral commissure. It is proposed that neurohemally released CaFl acts upon the albumen gland, whereas CaFl released from the collaterals may influence the activity of central neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426940 TI - In vitro biosynthesis of steroids, including 11-deoxycortisol and 5 alpha pregnane-3 beta,7 alpha,17,20 beta-tetrol, by ovaries of the goldfish Carassius auratus during the stage of oocyte final maturation. AB - To examine the production of steroids with potential oocyte maturation-inducing or pheromonal activity in the goldfish (Carassius auratus) we have incubated mature ovaries of this species with 17-[3H]hydroxyprogesterone. The metabolites in the unconjugated, glucuronide, and sulfate fractions were identified by chromatography, microchemical reaction, and, in most cases, crystallization to constant specific activity. A major metabolite, present in all three fractions, was tentatively identified as 5 alpha-pregnane-3 beta,7 alpha,17,20 beta-tetrol. Although 17,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) was found in only low yield (as a sulfate), the presence of the tetrol indicates that it is synthesized in high yield but very rapidly metabolized. The relative proportions of 17,20 alpha-dihydroxy-4-pregnen-3-one (17,20 alpha-P), 11-deoxycortisol (17,21 dihydroxy-4-pregnen-3,20-dione) and 17,20 beta,21-trihydroxy-4-pregnen-3-one (17,20 beta,21-P) varied significantly between incubations and may be affected by the maturational state of the ovary or the method used to stimulate oocyte maturation. Testosterone was present predominantly as its glucuronide. Significant production of glucuronides and sulfates was observed in all incubations. Twenty-five to 30% of the radioactivity remained associated with the tissue, but the distribution of activity between the metabolites did not differ greatly from that found in the medium. These results indicate that 11 deoxycortisol and its 20 beta-reduced derivative (17,20 beta,21-P) may be significant in spawning female goldfish. PMID- 1426941 TI - The primary structures of growth hormones of three cyprinid species: bighead carp, silver carp, and grass carp. AB - The primary structures of growth hormone (GH) of three cyprinid species, bighead carp, silver carp, and grass carp, were determined by a chemical method and/or by molecular cloning. The bighead carp GH was extracted from pituitary tissue by use of an alkaline medium, then successively purified by gel filtration, hydrophobic interaction column chromatography, and reverse-phase high-pressure liquid chromatography. The primary structure of bighead carp GH determined chemically is identical to that deduced from the cDNA nucleotide sequence. By molecular cloning, the primary structures of silver carp and grass carp GHs were also determined. The GHs of these three cyprinid species all contain 188 amino acid residues and their sequences are identical. When four of the five cysteines of cyprinid GHs were arranged to match the same positions of cysteines of other vertebrate GHs, a maximally matched alignment was achieved. Among fishes, GHs are relatively conserved within the same order (82 to 100% identity) but they are more diversified between orders (49 to 68% identity). In further comparison, fish GHs are even more different from tetrapod GHs (37 to 58% identity). Although the primary structures of vertebrate GHs are relatively variable, four homologous sequences, notably one located at the C-terminal, are found. PMID- 1426942 TI - Photorefractory Harris' sparrows (Zonotrichia querula) exposed to a winter-like daylength gradually regain photosensitivity after a lag. AB - The time course of regaining photosensitivity was monitored in intact and in castrated Harris' sparrows (Zonotrichia querula) held on short days. Measured endpoints, assumed to be equivalent indicators of the photosensitive state, were photoinduced testicular growth in intact males and a photoinduced elevation in plasma LH (luteinizing hormone) concentration in castrated males. Intact males were initially photorefractory when they were moved from long days to short days, and they remained so for at least 3 weeks thereafter. Photosensitivity was partially restored between Weeks 3 and 5 on short days and then gradually increased to a maximum by Week 13. No further change was detected through Week 25 on short days, when the experiment ended. Castrated males, also photorefractory when moved from long days to short days, regained photosensitivity as early as Week 7 on short days, but not uniformly until Week 16. As reflected by linear regression analysis, recovery of photosensitivity was a gradual process through Week 22 on short days, when the experiment ended. Discrepancies between intact and castrated males raise the possibility that the measured endpoints are not equivalent indicators of the photosensitive state. In accordance with an earlier report (Wilson, 1990), recovery of photosensitivity in castrated Harris' sparrows held on short days was not signaled by a spontaneous increase in plasma LH concentration. Indeed, plasma LH concentrations of castrated males remained suppressed even after photosensitivity had been fully restored in intact males. PMID- 1426943 TI - Testosterone-LH response and episodic secretion in the male marsupial, Dasyurus viverrinus. AB - The pattern of testosterone-LH secretion, feedback mechanism, and periodicity of release were investigated in the male marsupial eastern quoll. Testosterone secretion is controlled directly by LH and in the wild, the secretion of both are synchronous and show a major peak at breeding time. An inverse relationship between the secretion of LH and testosterone occurs after castration which supports the hypothesis that a negative feedback mechanism exists between the gonads and the pituitary gland as in other mammals. These hormones fluctuate in a cyclic manner over 24 hr. PMID- 1426944 TI - Plasma levels of sex steroids in the North Island brown kiwi (Apteryx australis mantelli) in relation to time of year and stages of breeding. AB - North Island brown kiwi (Apteryx australis mantelli) have a seasonal pattern of egg laying with a peak in mid to late winter. This study is the first description of changes in plasma steroid concentrations during the annual reproductive cycle of this species. Blood samples were collected at intervals over a 2 1/2-year period from a population of kiwi at Tangiteroria, Northland, New Zealand. Male kiwi had annual cycles of plasma levels of testosterone and estradiol. Mean testosterone levels were low (less than 0.18 ng/ml) during February to April, rose in May to a broad peak lasting 4 months (maximum levels 1.90 +/- 0.76 ng/ml), declined in September, and reached low levels in November to January. With respect to the breeding cycle, testosterone levels were low in the nonbreeding period, rose to high levels over 2 to 4 months before egg laying, then declined steadily toward the start of incubation. Plasma testosterone levels were very low in brooding males. Mean estradiol levels in males showed a pattern similar to testosterone levels, except that the rise to peak levels (1750 +/- 680 pg/ml) started in April. In female kiwi mean testosterone levels were low (less than 0.10 ng/ml) throughout the year. There was an annual cycle of mean estradiol levels in females which in timing and amplitude was similar to the male cycle. Estradiol levels in relation to stages of the breeding cycle in females were basal in the nonbreeding period, increased over a 3-month period before egg laying, declined in the 2 weeks before laying, and were low thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426946 TI - Evidence of a role for the turkey posterior pituitary in prolactin release. AB - The aims of this study were: (1) to examine whether the posterior pituitary contains prolactin releasing factor (PRF) activity, (2) to determine to what extent known neurohypophyseal peptides contribute to this activity, and (3) to compare posterior pituitary PRF activities of hens in different reproductive stages. Anterior pituitary cells derived from juvenile female turkeys were incubated with posterior pituitary extracts or test substances for 3 hr. Posterior pituitary extracts (0.1-0.8 equivalent) contained a potent substance(s) which stimulated PRL release in a concentration-dependent manner (2.4 +/- 0.08 to 6.5 +/- 0.23 micrograms/500 k cells). Arginine vasotocin (AVT) and vasoactive intestinal peptide (VIP) antisera (1:500) completely abolished the PRL-releasing activities of their respective peptides but partially reduced (P less than 0.05) the PRF activity of the posterior pituitary (AVT, 19.9%; VIP, 55.1%). Mesotocin antiserum did not alter (P greater than 0.05) PRL release induced by posterior pituitary extract. Posterior pituitary extract (0.01-0.5 equivalent) from hens in each of the various stages of the reproductive cycle induced a concentration dependent PRL release. The 0.5 posterior pituitary equivalent dose from reproductively quiescent (nonphotostimulated), laying, photorefractory, and incubating hens increased PRL release 2.4-, 2.9-, 3.8-, and 11.1-fold, respectively. The turkey posterior pituitary contains a potent PRF activity, partially accounted for by VIP and AVT, at the assayed concentrations, which varies with the reproductive cycle. PMID- 1426945 TI - Estradiol-17 beta secretion by the newly formed corpus luteum of a macropodid marsupial, the quokka (Setonix brachyurus). AB - The production of significant amounts of estradiol-17 beta from the 2-day-old corpus luteum of the macropodid marsupial, Setonix brachyurus (quokka), was shown using an in vitro perifusion system. Sliced corpora lutea and finely chopped extra-luteal ovarian tissue (cortex plus interstitial tissue) were perifused separately for 2 hr, in tandem for the next hour (with the perifusate from the ovarian tissue directed into the chamber containing the corpora lutea), and separately again for a further 2 hr. Overall production rates of estradiol measured by radioimmunoassay were 1.0 pg (mg hr)-1 from luteal tissue and 0.64 pg (mg hr)-1 from the extra-luteal tissue. Androgen production rates were 0.18 ng (mg hr)-1 and 0.06 ng (mg hr)-1 from luteal and extra-luteal tissues, respectively, and progesterone was produced at a rate of 0.80 ng (mg hr)-1 from luteal tissue and 16.5 pg (mg hr)-1 from extra-luteal tissue. Production rates of all three steroids from the perifused tissue increased significantly when the ovary and corpus luteum were perfused in tandem. The secretion of C19 and C18 steroids from the young corpus luteum suggests that luteinization is not yet complete at this stage in the reproductive cycle of the quokka, and the tissue would be better described as a "postovulatory follicle." This is supported in the literature by the occurrence of mitoses in granulosa cells for 6-7 days after resumption of the delayed cycle. This delayed maturation of the macropodid corpus luteum, which is associated with the secretion of significant quantities of estradiol and only a transient spike of progesterone, is discussed in relation to the longer cycles and gestation periods characteristic of macropodid marsupials. PMID- 1426948 TI - Sex steroid levels in the testes, ovaries, and pyloric caeca during gametogenesis in the sea star Asterias vulgaris. AB - The concentrations of progesterone, testosterone, and estradiol were determined via radioimmunoassay in testes, ovaries, and pyloric caeca of the sea star Asterias vulgaris during one complete and two partial gametogenic cycles. These compounds were found in all tissues examined and were present in quantities similar to those reported previously in other echinoderms and in vertebrates. Testes and ovaries exhibited annual growth cycles during which testicular and ovarian mass increased up to 100-fold as gametes were produced and stored until spawning. Pyloric caecal mass varied during the annual reproductive season; however, no seasonal trends were apparent. In the testes, sex steroid levels were highest at the onset of spermatogenesis. Transient increases in the levels of estradiol coincided with spermatogonial mitotic proliferation. Transient increases in the levels of testosterone and progesterone in the testes coincided with spermatogenic column formation and with spermiogenesis, respectively. In the ovaries, estradiol and testosterone levels were highest at the onset of oogenesis while progesterone levels did not change significantly throughout the annual gametogenic cycle. Male and female pyloric caeca exhibited similar seasonal variations in levels of sex steroids as compared with the gonads. It is hypothesized that transient increases in the levels of sex steroids during gametogenesis may serve as endogenous modulators of reproduction. PMID- 1426947 TI - Detection of the mRNA encoding vitellogenesis inhibiting hormone in neurosecretory cells of the X-organ in Homarus americanus by in situ hybridization. AB - Vitellogenesis inhibiting hormone (VIH)-mRNA in secretory cells of the eyestalk of Homarus americanus was detected by nonradioactive in situ hybridization (ISH) using two digoxigenin-tailed oligonucleotide probes deduced from the peptide sequence. Two distinct clusters of positive cells were observed in the medulla terminalis ganglionic X-organ (MGTX). Only one of them gave a strong immunoreaction after incubation with a specific polyclonal anti-VIH serum and corresponded to the conventionally described VIH producing cells. The significance of the cells reacting positively in ISH but not in immunocytochemistry (ICC) is discussed. Northern blot analysis using 32P-labeling confirms the specificity of the probes and indicates an approximate size of 2.5 kb for VIH mRNA. PMID- 1426949 TI - Changes in brain gonadotropin-releasing hormone, pituitary and plasma gonadotropins, and plasma thyroxine during smoltification in chinook salmon (Oncorhynchus tschawytscha). AB - Concentrations of brain salmon gonadotropin-releasing hormone (sGnRH), plasma gonadotropin I (GTH I), and pituitary GTH I and GTH II were determined in yearling chinook salmon (Oncorhynchus tschawytscha) during the parr-smolt transformation in two successive seasons. There were significant elevations in brain sGnRH content from February to March in 1988, and from February to April in 1989. Increases in brain sGnRH content coincided with elevations in plasma thyroxine levels that occurred from February to March, 1988 and 1989. Plasma GTH levels were relatively constant (1-2 ng/ml) throughout the period of sampling. However, during 1988, plasma concentrations of GTH I decreased significantly between late March and early April. During 1989, plasma GTH I levels appeared to reach a peak (2 ng/ml) in mid-February, but otherwise remained near 1 ng/ml. Previous studies have shown that GTH II was not detectable in plasma at this stage. During 1989, pituitary GTH I concentrations were 50- to 70-fold higher than that of GTH II, and increased, though not significantly, from February through April. Although GTH II was detected in the pituitary by RIA, it is likely that the measurable levels are due to GTH I cross-reaction in the GTH II RIA. Histological examination of the gonads indicated that throughout smoltification the oocytes remained in the perinucleolar stage of oogenesis and the testes were in the spermatogonial stage of spermatogenesis. Although no observable changes in gametogenesis occurred, the changes in brain sGnRH content, plasma GTH I levels, and pituitary GTH content suggest that some changes in the hypothalamic-pituitary axis may occur during smoltification. PMID- 1426950 TI - Reproduction in worker honey bees is associated with low juvenile hormone titers and rates of biosynthesis. AB - Three experiments were performed to determine the role of juvenile hormone (JH) in worker reproduction in queenless colonies of honey bees. In Experiment 1, egg laying workers had low hemolymph titers of JH, as did bees engaged in brood care, while foragers had significantly higher titers. Experiment 2 confirmed these findings by demonstrating that laying workers have significantly lower rates of JH biosynthesis than foragers do. In Experiment 3, ovary development was inhibited slightly by application of the JH analog methoprene to 1-day-old bees, but was not affected by application to older bees, at least some already displaying egg-laying behavior. These results, which are consistent with earlier findings for queen honey bees, are contrary to a common model of insect reproduction, in which elevated JH titers trigger ovary development, which then leads to oviposition. Previous experiments have demonstrated that JH regulates nonreproductive behavior in workers that is associated with colony division of labor; perhaps this function is incompatible with a traditional role for JH in reproduction. PMID- 1426951 TI - Effects of reproductive status, ovariectomy, and photoperiod on vasoactive intestinal peptide in the female turkey hypothalamus. AB - Vasoactive intestinal peptide (VIP) appears to be a physiologically relevant prolactin (PRL)-releasing factor during the avian reproductive cycle, yet little is known of the factors involved in modulating the hypothalamic concentrations of this neuropeptide. A heterologous chicken VIP radioimmunoassay was developed to examine the effects of reproductive status, ovariectomy, and photoperiod on hypothalamic VIP immunoreactivity in the female turkey. VIP concentrations were highest in the median eminence/infundibular nuclear complex (ME/INF) relative to other subregions of the hypothalamus and changed only in this region during the reproductive cycle. Quiescent, nonphotostimulated hens subjected to stimulatory photoperiod exhibited a 1.6-fold increase in VIP in the ME/INF (quiescent 59.9 +/ 6.0 vs photostimulated 95.8 +/- 7.1 pg/microgram protein). An additional 2-fold increase in ME/INF VIP concentrations was observed in laying hens (183.0 +/- 28.5 pg/microgram protein). Coincident increases in plasma PRL were also observed. In contrast, during incubation and the photorefractory stage, a dissociation between hypothalamic VIP and plasma PRL occurred. No changes were observed in VIP in incubating hens, yet a 6-fold increase in PRL was noted, compared to layers. In addition, ME/INF VIP concentrations exhibited no change during the photorefractory stage, whereas a 28-fold decrease in plasma PRL occurred. VIP concentrations in the ME/INF of laying hens were unaffected by ovariectomy, whereas exposure to short photoperiod reduced VIP by 44%. The inhibitory effects of short photoperiod could not be reversed by administration of exogenous steroids, while steroid treatment reduced VIP concentrations by 45% in the ovariectomized hens. These results provide additional correlative evidence for a modulatory role of VIP in PRL secretion and suggest that the expression of this neuropeptide in the INF may serve as a neural link between photoperiodic mechanisms and PRL release during the avian reproductive cycle. PMID- 1426952 TI - Purification, partial characterization, and heterologous radioimmunoassay of growth hormone (cGH) in red deer. AB - Red deer growth hormone (cGH; 3.3 mg) was purified from an aqueous extract of seven pituitary glands (4.01 g wet weight) by preparative gel filtration on Sephadex G-100, gel filtration on Sephadex G-100 SF, and anion exchange chromatography on DEAE-Sepharose CL-6B. Purified cGH gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight under reducing conditions of 20,000 Da and gave a single peak on reverse-phase high performance liquid chromatography. N-Terminal amino acid determination of 42 residues gave a sequence identical with those published for bovine and ovine GH. In a radioreceptor assay based on binding of iodinated recombinant bovine GH (rbGH) to liver microsomes prepared from a pregnant ewe, cGH was equipotent with an ovine GH (oGH) standard. In an oGH radioimmunoassay, cGH diluted in parallel with oGH and rbGH. Using this assay plasma GH concentrations were determined in adult nonpregnant red deer hinds over a 12-month period. There was a significant seasonality in plasma GH concentrations with concentrations consistently low between mid-May and mid-September. This is the period when voluntary food intake and liveweight gain are greatest. It is suggested that in the presence of low plasma GH concentrations nutrients may be diverted toward lipogenesis and hence promote fat deposition. PMID- 1426953 TI - Adrenal-kidney and gonadal steroidogenesis during sexual differentiation of a reptile with temperature-dependent sex determination. AB - Adrenal-kidney and gonadal steroidogenesis were studied during early development in the red-eared slider turtle, Trachemys scripta, which exhibits temperature dependent sex determination. In vitro steroid secretion by adrenal-kidney-gonad complexes (AKGs) incubated for 6 hr was determined by radioimmunoassay (RIA). AKGs from presumptive males and females secreted progesterone at developmental stages before (stage 15), during (stages 17 and 19), and after (stage 21) the temperature-sensitive period for sex determination, and progesterone secretion increased significantly throughout the period from stage 15 to 21. Presumptive male AKGs secreted significantly more progesterone than female AKGs at stage 19. Corticosterone secretion by AKGs was observed at stage 17 in males only, but in both sexes at stages 19 and 21. Testosterone, estradiol, androstenedione, and dehydroepiandrosterone secretion by AKGs was detected only at stage 21. Of the steroids measured, progesterone and corticosterone were consistently secreted at the highest levels. Although some sex differences were observed, no obvious patterns of sexually dimorphic steroid secretion from AKGs were apparent. Gonads from stage 21, stage 24, and 10-day-old hatchlings from both presumptive sexes incubated with [7-3H]pregnenolone showed only weak precursor conversion, primarily to polar metabolites, in incubations as long as 24 hr. None of the steroids assessed by RIA of AKG incubates could be identified by TLC or HPLC analysis of the stage 21 and stage 24 gonadal incubates. However, progesterone was tentatively identified in incubates of 10-day post-hatch female gonads. For stage 21 females, AKGs were separated into gonadal and adrenal-kidney tissue (AK) components and incubated in vitro for 1, 3, and 18 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426954 TI - Isolation of maturational gonadotropin subunits from spotted seatrout (Cynoscion nebulosus) and development of a beta-subunit-directed radioimmunoassay for gonadotropin measurement in sciaenid fishes. AB - Maturational gonadotropin (GTH) subunits were isolated from pituitaries of the spotted seatrout (Cynoscion nebulosus), a marine perciform teleost, by ethanolic extraction and ion-exchange, gel-filtration, and reverse-phase chromatography. Partial amino acid sequencing of the N-terminal regions of the alpha and beta subunits indicated 60-80% identities with various carp and salmon GTH subunits. The spotted seatrout GTH beta-subunit was used as radioligand in a radioimmunoassay (RIA) with Atlantic croaker (Micropogonias undulatus) GTH antiserum. Pituitary extracts and plasmas from a variety of sciaenid fishes diluted parallel to the croaker GTH standard in the RIA. These data suggest that there is a high degree of immunological similarity among the GTH beta subunits of sciaenid fishes. The RIA measured increased levels of GTH in the plasmas of three species of sciaenid fishes, spotted seatrout, orangemouth corvina (Cynoscion xanthulus), and red drum (Sciaenops ocellatus), following injections of a luteinizing hormone-releasing hormone analog. The beta-subunit-directed GTH RIA increases considerably the number of species in which studies of GTH physiology can now be conducted. PMID- 1426955 TI - Temperature, but not photoperiod, influences gonadotropin-releasing hormone binding in the pituitary of the three-spined stickleback, Gasterosteus aculeatus. AB - Gonadotropin-releasing hormone (GnRH) binding characteristics in pituitaries of stickle-backs under different physiological conditions were studied using D-Arg6 Pro9-salmonGnRH-NEt as labeled ligand. Both males and females displayed marked seasonal changes in the capacity of high-affinity GnRH binding sites; there was a high content in the breeding season (summer) (800-1500 pmol/pituitary) and no detectable high affinity (< 150 pmol) binding in late winter-early spring. The binding capacity was lower in postbreeding fish (ca. 400 pmol/pituitary in females, ca. 900 pmol in males) than in breeding fish (females: ca. 1850, males ca. 1400 pmol). GnRH binding sites were also studied in fish exposed to long and short photoperiod in combination with high and low temperature in winter. Only long photoperiod in combination with high temperature stimulated sexual maturation. The capacity of the GnRH binding sites was similar in fish exposed to long (females 1550 pmol, males 1000 pmol) and short (females 1800, males 900) photoperiod in combination with high temperature. In fish exposed to low temperature, binding was nondetectable irrespective of the photoperiod. PMID- 1426956 TI - Ovarian development and correlated changes in hemolymphatic ecdysteroid levels in two spiders, Coelotes terrestris and Tegenaria domestica (Araneae, Agelenidae). AB - Oocyte development during the first vitellogenic cycle of Coelotes terrestris and Tegenaria domestica is described. Under the present conditions, this development took about 40 days during which the oocytes went through six stages of maturation. For the first time presence of ecdysteroids is reported in adult females of spiders. Hemolymphatic ecdysteroid peaks were observed in both species at the transition between previtellogenesis and vitellogenesis. 20 Hydroxyecdysone and ecdysone were present in slightly different ratios in C. terrestris as well as T. domestica. These data largely agree with current views of ovarian development in Arthropods. PMID- 1426957 TI - Immunoreactive Met-enkephalin-like material in the testis of Rana esculenta: identification and localization. AB - Methionine-enkephalin (Met-Enk) has been detected in the testis of the frog, Rana esculenta, using a reverse-phase high-performance liquid chromatography system coupled with a specific radioimmunoassay. By means of immunocytochemical techniques Met-Enk positive cells have been localized in interstitial and germinal compartments. Particularly, spermatogonia, spermatocytes, and spermatozoa were stained in seminiferous tubules, and numerous interstitial cells showed strong cytoplasmic immunoreactivity in summer animals. Variations in the concentration of Met-Enk immunoreactive material occurred during the annual cycle. Our data show that Met-Enk is present in testes of nonmammalian vertebrate species. These results suggest that autocrine and/or paracrine mechanisms may regulate testicular activity in amphibians. PMID- 1426958 TI - The complete amino acid sequence of the follitropin beta-subunit of the bullfrog, Rana catesbeiana. AB - The amino acid sequence of the bullfrog, Rana catesbeiana, follitropin beta subunit has been determined by sequencing the intact protein (residues 1-39) and peptides originated by lysyl endopeptidase and pepsin. Twelve cysteine residues and two sugar chain binding sites at Asn-5 and Asn-22 are positional identities with bullfrog and mammalian beta-subunits. The bullfrog FSH beta-subunit is composed of 107 amino acid residues with a molecular mass of 11,782 Da, including the six cystine bridges and excepting the sugar chain. The bullfrog FSH beta subunit has approximately 60% sequence identity with that of mammals and 40% with the fish gonadotropin beta-subunit. Conserved sequences among mammals (residue numbers 33-55 and 66-71) extensively differed from those of the bullfrog. PMID- 1426960 TI - Abnormal growth hormone receptor gene expression in the sex-linked dwarf chicken. AB - Sex-linked dwarfism is a recessive mutation that causes a reduction in body weight gain and long bone growth of chickens. We examined the effect of the dwarfing gene on body weight, hepatic GH-binding activity, and the structure and expression of the growth hormone receptor (GHR) gene in two different lines of sex-linked dwarf (SLD) broiler chickens. Liver samples from one line of dwarf chicken were obtained from Arbor Acres Farm, Inc. (Glastonbury, CT) and fertile eggs from the second line of SLD were obtained from the University of Georgia. In the GA line, the average body weight of homozygous (dwdw) males at 11 weeks of age was 43% lower than that of normal (DwDw) males, while heterozygous (Dwdw) males were only 9% below normal. In the CT line, hepatic GH-binding activity of 35-week-old chickens was high (20% specific binding) in normal (DwDw) males and undetectable in liver membranes prepared from dwdw males. At 11 weeks of age, hepatic GH-binding activity of Dwdw males (3.9% specific binding) in the GA line was reduced by 44% and that of dwdw males was almost undetectable (0.34% specific binding) when compared to the average of normal GA males (7.1% specific binding). Southern and Northern blot analyses revealed different abnormalities in the GHR gene from the two separate lines of SLD. A restriction fragment length polymorphism in DNA and an aberrantly sized transcript (mRNA) were detected in the CT line of SLD chickens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1426959 TI - In vitro steroid secretion by staged spermatocysts (Sertoli/germ cell units) of dogfish (Squalus acanthias) testis. AB - Using the dogfish shark (Squalus acanthias) testis model in which different germ cell stages are topographically separated, we previously observed that steroidogenic enzyme activities vary qualitatively and quantitatively during spermatogenesis. To determine whether these data, obtained by radiolabeled tracer analysis of testicular microsomes, accurately predict steroid secretion by intact cultured spermatocysts (germ cell/Sertoli cell units), steroids were radioimmunoassayed directly in spent medium. Steroid output in basal medium was low, but after addition of 25-hydroxycholesterol (25-OH chol, 60 microM), large amounts of progestins (P) and testosterone (T) accumulated. Dehydroepiandrosterone (DHEA), androstenedione (A), and estradiol (E2) were low or nondetectable in the presence or absence of 25-OH chol; however, addition of T (1 microM) as substrate elevated E2 above assay limits. T and P contents of media increased progressively over a 24-hr culture period (Day 1). Replacement and analysis of spent media at 24-hr intervals indicated that secretion was continuous up to 6 days after seeding, although secretory rates (T plus P) and T/P ratios changed with time in culture. Spermatocysts in premeiotic (PrM), meiotic (M), and post-meiotic (PoM) stages all secreted T and P; however, absolute values, T/P ratios, and stage-dependent patterns varied from one experiment to another with no obvious seasonal pattern. Also steroid secretion by staged cysts did not consistently agree with predictions based on steroidogenic enzyme activities measured in earlier cell-free assays, whether or not 25-OH chol was present. This discrepancy was not explained by stage-related patterns of steroid secretion vs retention or by addition of putative in vivo regulators. Agents that elevated P and/or T were dibutyryl cyclic AMP, 1-isobutyl-3 methylxanthine (IBMX), and forskolin, whereas ventral lobe extract and Ca2+ ionophore (A23817) were inhibitory. An autoregulatory feedback loop was indicated by a negative relationship between cyst concentration per well and steroid secretion rate. In contrast to T and P, E2 secretion in the presence of substrate (T, 1 microM) was as predicted from previously determined patterns of aromatase activity (M > PrM > PoM) and increased in response to IBMX. Added [3H]P, [3H]T and [3H]E2 all were extensively metabolized to polar products and P metabolism was stage related (PoM > M > PrM). These data indicate that analysis of free P, T, and E2 in static cyst cultures may underestimate true steroidogenic potential. Assuming further characterization of the system, we conclude that cultured spermatocysts from dogfish testis have potential for studying the multifactorial regulation of steroid synthesis and secretion stage-by-stage during spermatogenesis. PMID- 1426961 TI - Induction by beta-estradiol of vitellogenin in striped bass (Morone saxatilis): characterization and quantification in plasma and mucus. AB - Striped bass (Morone saxatilis) were implanted with beta-estradiol to induce the production of vitellogenin, the egg yolk precursor produced by the liver. Electrophoretic analysis revealed that beta-estradiol caused marked production of a plasma protein of apparent molecular mass 170 kDa. Size exclusion chromatography suggested that the estradiol-induced protein circulated as a dimer. This protein was purified from the plasma of estradiol-treated fish by DEAE-agarose column chromatography and used to induce antibodies in rabbits and goats. Western blots revealed that the antiserum bound to the putative vitellogenin in plasma from estradiol-treated fish and adult females, but not with any proteins in male plasma. Western blot of ovarian extract revealed several smaller immunoreactive protein bands and supported the identity of the purified protein as vitellogenin. A competitive ELISA was developed with sensitivity in a range from 8 to 1000 ng/ml. Plasma concentrations of adult females during their spawning migration ranged from 100 to 600 micrograms/ml. Western blot of mucus extract revealed the presence of a 170-kDa protein in vitellogenic female fish along with several minor bands ranging from 50 to 110 kDa. Positive immunoreactivity was present in the surface mucus of all females and in none of the males collected during a spawning migration in the Hudson River. PMID- 1426962 TI - Evidence for the colocalization of gastrin/CCK- and PYY/PP-immunoreactive substances in the small intestine of the lizard Podarcis hispanica: immunocytochemical and ultrastructural study. AB - Peptide tyrosine tyrosine/pancreatic polypeptide (PYY/PP)- and C-terminal gastrin/cholecystokinin (G/CCK)-immunoreactive cells were investigated in the intestine of the lizard Podarcis hispanica, using immunocytochemistry with light and electron microscopy. Immunolabeling of consecutive semithin sections revealed coexistence of PYY/PP- and C-terminal G/CCK-like substances in some cells, while in others only PYY/PP or G/CCK immunoreactivity was found. Appropriate absorption controls excluded cross-reactivity between the antisera used. Ultrastructurally G/CCK+, PYY/PP+ cells were similar to G/CCK+, PYY/PP- cells but different from PYY/PP+, G/CCK- cells. Although virtually nothing is known concerning the physiological effects of these peptides in reptiles, their colocalization in the same cells in the intestine of Podarcis hispanica suggests a close relationship between them in the regulation of the digestive process. PMID- 1426963 TI - Effect of breeding state, moulting, dehydration, exposure to saturated atmosphere, and arginine vasotocin on cutaneous water permeability in the toad Bufo bufo. AB - Cutaneous water permeability was assessed in hydrated male toads under a variety of conditions, including dehydration and rehydration, and the effects of exogenous arginine vasotocin (AVT) were determined. Cutaneous water permeability (the rate of water uptake by toads in water) was high in toads collected in the breeding pond and declined steeply during the first week, coincident with reduced activity of the cutaneous mucus glands. The slopes of the dose-response curves relating AVT to cutaneous water influx were about the same at the transition from the breeding to the nonbreeding state, but the level of influx was higher in the breeding state. The dose-response relationship in long-term terrestrial acclimated toads was similar to that in water-acclimated toads. The threshold dose for effect on the cutaneous water permeability was about 1 ng AVT. Dehydration had a substantially greater effect on the cutaneous water permeability than AVT. The ratio between dehydration and AVT responses tended to increase with increasing water transport capacity of the skin. Moulting and acclimation to a saturated atmosphere in fully hydrated toads more than doubled the water permeability and abolished the response to AVT. It is suggested that AVT and other factors increase the cutaneous water permeability by similar mechanisms, such as insertion of water channels in the apical membrane of the epidermal cells. The effect of AVT on the toad skin is interpreted as reflecting the general high potency of neurohypophysial hormones in stimulating the water permeability of membranes of variable permeability. PMID- 1426964 TI - Lack of control of renin release by adrenergic nervous system in the aglomerular toadfish. AB - Aglomerular toadfish, Opsanus tau, release renin in response to hemorrhage or vasodilator drugs, presumably by stimulating a renal arterial baroreceptor. We aimed to determine whether the adrenergic nervous system and prostaglandins play a role in the control of renin release in unanesthetized toadfish kept in 50% seawater. Isoproterenol (1 microgram/kg) increased plasma renin activity (PRA) fourfold and decreased blood pressure (BP); both effects were abolished by a concomitant infusion of propranolol. Propranolol itself slightly decreased the basal level of heart rate and BP, but not that of PRA. Norepinephrine (1 microgram/kg) increased BP, but did not change PRA. Repeated injection of 6 hydroxydopamine did not alter resting levels of either PRA or BP. Monoamine specific nerve fluorescence activity could not be demonstrated in association with arterioles of kidneys from intact toadfish or from those treated with monoamine oxidase inhibitor and norepinephrine (5 mg/kg). Furthermore, treatment of toadfish with indomethacin (10 or 20 mg/kg) prevented neither the increase in PRA nor the reduction in BP after a massive hemorrhage. These results indicate that renin release in toadfish primarily occurs in response to a reduction in renal arterial pressure, whereas it appears unlikely that the adrenergic nervous system or prostaglandins have a significant role in the control of renin release. PMID- 1426965 TI - In vivo studies on the effects of ovine corticotrophin-releasing hormone, arginine vasotocin, arginine vasopressin, and haloperidol on adrenocortical function in the racing pigeon (Columba livia domestica). AB - This study investigates the effects of in vivo administration of pituitary stimulants in racing pigeons (Columba livia domestica). Plasma corticosterone concentrations were measured following intravenous administration of ovine corticotrophin-releasing hormone (oCRH) (0.1, 1, 10, and 100 micrograms/kg), arginine vasopressin (AVP) (0.01, 0.1, 1, and 10 micrograms/kg), arginine vasotocin (AVT) (0.01, 0.1, 1, and 5 micrograms/kg), and haloperidol (0.05, 0.5, and 5 micrograms/kg). Compared with mammals the pituitary-adrenocortical system of the pigeon appeared to be less sensitive to stimulation with oCRH, although high doses were well tolerated and gave a clear response. Both AVP and AVT stimulated corticosterone secretion, AVT in a more pronounced dose-dependent manner than AVP. The natural neurohypophysial peptide in birds, AVT, was less well tolerated in high doses than AVP. The clear response to haloperidol indicates that the hypothalamo-pituitary-adrenocortical system is under dopaminergic inhibition. Of the pituitary stimulants tested AVP (10 micrograms/kg) and oCRH (100 micrograms/kg) are the most appropriate for testing the integrity of the pituitary-adrenocortical system in the pigeon. PMID- 1426966 TI - Prolactin and gonadal steroids during the reproductive cycle of the Bengalese finch (Lonchura striata var. domestica, Estrildidae), a nonseasonal breeder with biparental care. AB - Plasma levels of prolactin (Prl), testosterone (T), and progesterone were determined throughout the breeding cycle in pairwise caged Bengalese finches (Lonchura striata var. domestica, Estrildidae), a monogamous altricial passerine with nonseasonal breeding, in which parental behavior including incubation is equally shared between males and females. In both sexes, Prl titers increased 4- to 10-fold during incubation period compared to values during nestbuilding. Likewise, Prl levels after fledging of the young were significantly lower compared to titers during incubation. In males, T increased significantly (15 fold) during nestbuilding compared to all other stages of the breeding cycle. In females, T remained basal throughout the entire breeding cycle. Thus, T levels were elevated only during stages with low Prl titers and vice versa. Progesterone titers were elevated during egg-laying in females and fluctuated without any obvious pattern in males. These results suggest that (1) high levels of Prl are involved in the control of parental behavior of male and female Bengalese finches and (2) Prl secretion is controlled by proximate factors of the early reproductive cycle since reproduction is independent of seasonal factors in this species. PMID- 1426967 TI - Lorenz-Mie light scattering in cellular biology. AB - The Lorenz-Mie light scattering is discussed as a tool allowing living cell characterization. The scattered light carries information about the size, shape, internal structure and refractive index of the cell. The advantages of light scattering methods consist in high speed, nondestructive, sensitive and relatively easy measurements. Light scattering methods are compatible with other methods. In light scattering in both static and flow systems. For sphere-like cells reliable size and refractive index information can be extracted. On the empirical basis, light scattering pattern can be used for the cell identification and separation purposes. The full utilization of the light scattering information is limited due to the lack of theoretical knowledge about the complex scatterer properties and efficient inversion schemes. The rapid progress in computer technique and in single-particle scattering experiments may significantly improve the interpretation of light scattering patterns of the biological particles. PMID- 1426968 TI - Ionic requirements for the activation of contraction in embryonic frog myoblasts in culture. PMID- 1426969 TI - Studies of osmo-diffusive and energetic properties of the maize root. AB - This work is concerned with osmotic and diffusive transport of water and solutes across the maize root, and also with ascent of substances in the xylem. The root has been modelled as a one-membrane system. For the root treated in this way (and with the stem cut off) all the transport parameters present in the thermodynamic description of transport (Katchalsky and Curran 1965) were determined using the pressure probe method (Steudle et al. 1987). These parameters include coefficients of filtration Lp, reflection sigma, and permeability omega. Using numerical values of the parameters and the formalism mentioned, detailed calculations were performed of osmotic volume flows Jv, and solute flows js, going across the maize root and pumped by the root up to a certain height h, against the force of gravity. This in turn allowed, with the use of a previously developed analytical method (Kargol 1990) to study the osmo-diffusive conversion of free energy of solutions, and to analyse the root as a free energy converter. In particular, the effective power and energetic efficiency of the root in the radial transport and pumping of water by the root pressure up to a certain height h, were studied. The root pressure has been assumed to be generated osmotically. PMID- 1426970 TI - Polyamines as modulators of lipoperoxidation. AB - The polyamines spermine and spermidine and the diamine putrescine inhibit lipid peroxidation in phospholipid liposome suspensions and rat liver homogenates. Using the chemiluminescence technique the antioxidant activity of polyamines was found to be due to reactions with the free radical intermediates of lipid peroxidation and/or superoxide radicals. Also, the antioxidant action of polyamines correlated with the amount of their amino groups: the antioxidant activity increases from putrescine to spermine. PMID- 1426971 TI - Bile salts binding-induced alterations in ultraviolet absorption spectrum of bovine serum albumin. PMID- 1426972 TI - Role of electrostatic forces in hydroxy and keto bile salt-albumin interactions: some experimental observations. AB - Proton binding to bovine serum albumin and effects on hydroxy and keto bile salts albumin binding were studied within a pH range between 5 and 10. Electrostatic forces contribute to the binding of these ligands to albumin; prototropic groups of albumin such as imidazol are involved in the interaction. Bile salts binding produces a shift in pK of these groups. It is postulated that hydroxy bile salt albumin binding is linked with the N in equilibrium with B transition of the protein, while for keto bile salts a microarrangement in the protein binding sites is driving the interaction. PMID- 1426973 TI - Thermally-induced delayed fluorescence of photosystem I and II chlorophyll in thermophilic cyanobacterium Synechococcus elongatus. AB - Stationary delayed fluorescence (DF) of chlorophyll in isolated membrane preparations from thermophilic cyanobacterium Synechococcus elongatus was investigated as a function of temperature. Two peaks at different temperatures were observed. The low-temperature peak (54-60 degrees C) coincided with the main maximum of the thermally-induced delayed fluorescence of chlorophyll in intact cells and PSII-particles with active oxygen-evolving system. The high-temperature peak (78 degrees C) coincided with the minor band of delayed light emitted by intact cells. It was also observed in the delayed fluorescence emission from a PSI-enriched fraction preparation. The intensities of the DF peaks were dependent on the presence of inhibitors, donors and acceptors that cause specific effects on electron transport of the two photosystems. The low-temperature and high temperature peaks were related to PSII and PSI, respectively. The manifestation of delayed fluorescence from PSI and PSII at different temperatures seems to be a specific property of thermophilic cyanobacteria. The reason for this may be a high thermal stability of the photosystems and the lack of the PSII antenna complex in isolated membranes. Consequently, the relative yield of delayed fluorescence from PSI markedly increases. Thermally-induced fluorescence seen in membranes of cyanobacteria showed a high sensitivity to structural and functional membrane alterations induced by pH changes, different electron transport stabilizing agents or different concentrations of MgCl2. PMID- 1426974 TI - Anthroylcholine bromide: a fluorescent ligand for the muscarinic receptor. AB - The action of anthroylcholine bromide, a new fluorescent probe, has been studied at the cellular (contraction of intestinal muscle) and subcellular levels (binding of 3H-quinuclidinyl benzilate to brain cortex membranes, fluorescence and enzyme activity) with the following results: 1. Anthroylcholine bromide competitively antagonized the contractile effect of acetylcholine in isolated rat duodenum (pA2 = 6.12), but had no effect either on the concentration response curves to histamine or to noradrenaline in isolated guinea pig ileum and rat vas deferens. 2. Anthroylcholine bromide displaced competitively 3H-quinuclidinyl benzilate from brain cortex membranes (Ki = 0.77 mumol/l). 3. Direct binding to the muscarinic site could be measured by exploiting the fluorescence properties of the probe. Binding displaceable by atropine (approximately 20% change in fluorescence) had an apparent affinity constant similar to that found with indirect methods. In contrast, d-tubocurarine did not displace the probe from its site, and atropine- or d-tubocurarine-sensitive binding of anthroylcholine bromide to Torpedo marmorata electric organ membranes, rich in nicotinic receptors, was not observed. These properties suggest the applicability of the probe to study the distribution, structure and/or kinetic properties of the muscarinic receptor. PMID- 1426975 TI - Interactions of selected insect neuropeptides with synthetic lipids. AB - Interactions of the insect neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr), its [beta-cyclohexyl-(4-O-methyl)2]-L-alanine analog, and the leucopyrokinin [2-8] fragment (Thr-Ser-Phe-Thr-Pro-Arg-Leu-NH2), with synthetic phospholipids (DPPC, DMPE, DMPG) were studied using the microcalorimetric method. Most pronounced changes of the lipid thermotropic behavior were observed with DMPG/leucopyrokinin [2-8]-fragment mixtures. Proctolin itself was less active with all the lipids studied. The results obtained suggest that the studied peptides interact with the head group region of lipid bilayer. PMID- 1426976 TI - Partition of piperidinoethylesters of 2-alkyloxyphenylcarbamic acid in unilamellar phosphatidylcholine liposomes. AB - Molar partition coefficients for amphiphilic N-[2-(2-alkyl-oxyphenyl carbamoyloxy)-ethyl]-piperidinium chlorides (PAA) between small unilamellar egg yolk phosphatidyl choline liposomes and saline, as determined by ultraviolet difference spectroscopy at 22 degrees C, pH 5-6, v = 34640 cm-1, and at 100 mumol/l PAA concentration, were 149, 1990, and 7474 for PAA with 5, 7, and 9 carbon atoms in the alkyloxy substituent, respectively. At the PAA concentration used, the cut-off in biological activities of PAAs with long alkyloxy substituents could not be caused by the self-association of PAA molecules in the aqueous phase. PMID- 1426977 TI - Non-enzymatic glycosylation of myosin: effects of diabetes and ageing. AB - The influence of diabetes mellitus, streptozotocin-induced diabetes and ageing on the non-enzymatic glycosylation of myosin from cardiac and skeletal muscles was investigated. In cardiac muscle, and to a lesser extent also in skeletal muscles of the rat, non-enzymatic glycosylation of myosin increases with the age, as measured in 6-, 12- and 29-month-old animals. Skeletal muscle myosin from diabetic humans and also that from diabetic rat cardiac muscle are more glycosylated when compared with control myosin preparations. Ca(2+)-ATPase activity of myosin is lower in muscles of diabetic individuals as compared with control muscles. PMID- 1426978 TI - Activation heat in various cross-striated muscles of Rana esculenta: microcalorimetric measurements. AB - Activation heat (AH) is an important component in energy balance of muscle contraction. It represents energy dissipation of biochemical processes enabling muscle in rest to perform contraction. According to our measurements on intact muscles, AH is 20% of initial heat production in twitch, and 10% in tetanus. Significantly different AH values have been obtained for muscles of parallel and not parallel fibre architecture. PMID- 1426979 TI - Effect of lipid peroxidation on molecular arrangement of phospholipids in liposomes prepared from egg yolk phosphatidylcholine or total rat brain lipids. A 31P NMR study. AB - Changes in molecular arrangement of membrane phospholipids in the course of lipid autoxidation were studied by means of broad-band 31-P NMR spectroscopy. Multilamellar liposomes prepared from egg yolk phosphatidylcholine (PC) or total lipid extracts from rat brains (TL) were used as models. The initial lamellar arrangement of phospholipids of both types changed as lipid peroxidation proceeded and a narrow isotropic signal appeared in the spectra at 0 ppm, this phenomenon being more prominent for TL than for PC. Probably the isotropic signal represents some nonlamellar structures within the membranes of peroxidized lipids. PMID- 1426980 TI - Haematoporphyrin changes the mechanical properties of lipid bilayer membranes. AB - The interactions between haematoporphyrin (HP) and bilayer lipid membranes (BLM) were studied. A weak effect of HP on BLM conductivity was observed at HP concentrations ranging between 10(-6) and 3 x 10(-5) mol/l. Modulus of elasticity in the direction normal to the membrane plane (E perpendicular) and dynamic viscosity coefficient (eta) were measured, both exhibiting HP-induced decrease by 22-31% in the dark. In this case, membrane potential Vm became negative and reached a value close to -50 mV. Under illumination by low-intensity (1 mW) He-Ne laser (lambda = 632 nm) the values of parameters E perpendicular and eta of the HP-modified membranes increased by 41-66%, and Vm decreased to -20 mV. Upon removing HP from the solution by perfusion, irreversible changes in mechanical properties of the HP-modified membranes induced by the laser light were observed. The reason could be the formation of stable complexes of HP with the lipid molecules. HP binds to membrane noncooperatively, with a binding constant K approximately 10(5) l/mol. PMID- 1426981 TI - Hydroosmotic activities of arginine-vasopressins modified either in positions 1, 2 and 4 or at N-terminal extensions. AB - Vasopressin and its synthetic analogs were studied for their effect on transepithelial water flux in frog urinary bladder. As compared with AVP, 1 deamino-8-D-arginine vasopressin (dDAVP) was about 40 times less effective in stimulating osmotic water flow. The vasopressin analogs obtained by modification in positions 1 and 2 were: [1-(1-mercapto-4-tert-butylcyclohexaneacetic acid)] AVP (I); [1-(1-mercapto-4-methylcyclohexaneacetic acid)]AVP (II); [1-(1-mercapto 4-methylcyclohexaneacetic acid)-2-O-methyltyrosine]AVP (III); and those modified in position 4 were: [1-(1-mercaptocyclohexaneacetic acid)-4-arginine] AVP (IV); [1-(2-mercaptopropionic acid)-4-arginine]AVP (V). Any of the above analogs did not influence basal, but antagonized vasopressin-stimulated water flux. N terminally extended analogs of AVP: Ala-AVP (VI); Ser-Ala-AVP (VII) and Thr-Ser Ala-AVP (VIII) stimulated osmotic water flux to the same extent in concentration 200 times higher as that of AVP. We conclude from these studies that vasopressin analogs (I-V) competitively antagonize vasopressin-stimulated hydroosmotic activity in frog urinary bladder probably at the epithelial vasotocin V1 and/or V2 receptor site. N-terminal extension of the vasopressin molecule did not influence the capacity of AVP to induce V2 receptor-mediated action, even when used at higher concentrations. PMID- 1426982 TI - Plasmid transformation of Ruminococcus albus by means of high-voltage electroporation. AB - To apply recombinant DNA techniques to the genetic manipulation of cellulolytic ruminal bacteria, a plasmid vector transformation system must be available. The objective of this work was to develop a system for plasmid transformation of Ruminococcus albus. Using high voltage electrotransformation, pSC22 and pCK17 plasmid vectors, derived from lactic acid bacteria plasmids and replicating via single-stranded DNA intermediate, were successfully introduced into three freshly isolated R. albus strains and into R. albus type strain ATCC 27210. The optimization of the electrotransformation condition raised the electroporation efficiency up to 3 x 10(5) transformants per microgram of pSC22 plasmid. PMID- 1426983 TI - Evidence that Borrelia burgdorferi immunodominant proteins p100, p94 and p83 are identical. AB - Recently there have been reports on high-molecular mass components of Borrelia burgdorferi, namely the p100, p94 and p83, which claimed these proteins to be specific marker antigens for the serodiagnosis of late Lyme borreliosis. The nucleotide sequences of the p100 and p83 have been published. The alignment of the deduced N-terminal amino acid sequences with the N-terminal sequence of the p94 now provides evidence that all three proteins are identical. PMID- 1426984 TI - Acid phosphatase activity of promastigotes of Leishmania donovani: a marker of virulence. AB - Seven cloned lines of promastigotes of Leishmania donovani (UR 6) were isolated by limiting dilution. One clone, UR6-C25, failed to multiply inside the macrophages of line J774G8 and thus was labelled as avirulent. Another, UR6-C24, multiplied inside macrophages, had a virulence index as high as 93 +/- 9.8 and was thus labelled as highly virulent. The other five clones had variable degree of virulence indices ranging from 46.4 +/- 5.8 to 67.6 +/- 3.5. No significant difference in the degrees of attachment of virulent and avirulent populations of promastigotes to macrophages was observed, suggesting no difference in the ligand utilised by these populations for attachment to the macrophages. Acid phosphatase activity of cloned promastigotes correlated with the degree of virulence. These data suggest that acid phosphatase activity could be used as a marker to differentiate avirulent from virulent populations of promastigotes of L. donovani. PMID- 1426985 TI - Purification and properties of pyruvate kinase from Thermoplasma acidophilum. AB - Thermoplasma acidophilum is a thermoacidophilic archaebacterium occupying a paradoxical place in phylogenetic trees (phenotypically it is a thermoacidophile but phylogenetically it classifies with the methanogens). To better understand its phylogeny, the pyruvate kinase from this organism is being investigated as a molecular marker. The enzyme has been purified and has a native M(r) of 250,000. It consists of four, apparently identical subunits each of M(r) 60,000. No remarkable kinetic differences have been found between this thermophilic enzyme and its mesophilic counterparts other than its greater thermostability. Its amino acid composition has been determined and some partial sequencing has been done. PMID- 1426986 TI - Immunocharacterization of actin and its immunofluorescent localization during the developmental gametophytic stages of Allomyces arbuscula. AB - Highly specific polyclonal antibodies against actin from Allomyces arbuscula were produced in rabbits, immunopurified by immunoblotting and specified with actin isolated from Neurospora crassa and mouse skeletal muscle. Used as immunofluorescence probes, they allowed localization of actin in the sequential gametophytic stages of the mould. PMID- 1426987 TI - Dechlorination of 2,3,5,6-tetrachlorobiphenyl by a phototrophic enrichment culture. AB - A phototrophic enrichment culture, using acetate as carbon source, reductively dechlorinated 2,3,5,6-tetrachlorobiphenyl. ortho chlorines were removed preferentially over meta chlorines. Tri- and dichlorobiphenyls were the major products. During 14 months incubation, chlorine was removed from 58% of the target molecules; 19% of the total chlorines were removed. Dechlorination did not occur in a control culture incubated in the dark. PMID- 1426988 TI - The nysB sunD double mutant of Dictyostelium discoideum is blocked in the acquisition of non-degradative resistance to the pea phytoalexin pisatin. AB - Dictyostelium discoideum amoebae can be induced to acquire a non-degradative resistance to the pea phytoalexin pisatin. The nysB sunD double mutant is blocked in the acquisition of this resistance. Using parasexual genetics it has been shown that sunD is a recessive mutation linked to nysB on linkage group VI. PMID- 1426989 TI - Plasmid transfer by conjugation in Desulfovibrio desulfuricans. AB - Conjugational transfer of several IncQ plasmids from Escherichia coli to the strictly anaerobic, sulfate-reducing bacterium Desulfovibrio desulfuricans strain G100A was demonstrated. Plasmid DNA from exconjugants was visualized on agarose gels and was used to transform E. coli to the appropriate antibiotic resistances. Neither transfer of IncW and IncP plasmids to strain G100A, nor transfer of any plasmid to D. desulfuricans strain ATCC 27774 was observed. Conjugation of suicide plasmids containing either Tn5 or Tn9 into D. desulfuricans did not result in detectable transposition. Optimal conditions for conjugational transfer and antibiotic resistance levels of strain G100A were examined. PMID- 1426990 TI - Isolation and sequence of a 2-kbp miniplasmid from Bacillus thuringiensis var. kurstaki HD-3a3b: relationship with miniplasmids of other B. thuringiensis strains. AB - The miniplasmid profiles of 18 Bacillus thuringiensis strains belonging to 8 different serotypes were determined using an alkaline hydrolysis method for isolation of low molecular mass plasmids. Nearly all the strains contained covalently closed circular (CCC) DNA species ranging from 2 to 5 species per strain and from 1.5 to 10.5 kbp in size (values corresponding to CCC forms). A 2 kbp plasmid from B. thuringiensis var. kurstaki HD-3a3b futura strain was used in Southern hybridization experiments to analyse relationships among the low molecular mass plasmids of different B. thuringiensis strains. This 2-kbp miniplasmid was present in most strains which show toxicity against lepidoptera. It was not present in those strains toxic against diptera (B. thuringiensis var. israelensis) or coleoptera (B. thuringiensis var. tenebrionis). The 2-kbp miniplasmid from B. thuringiensis var. kurstaki HD-3a3b futura was cloned and fully sequenced. Sequence analysis of the 2058 bp of the miniplasmid revealed the presence of an ORF (630 bp, 210 amino acids in size) that is preceded by a consensus sequence of B. thuringiensis crystal protein gene transcription promoters. No significant homology was observed with known B. thuringiensis toxin nucleic acid sequences or with other known sequences. PMID- 1426991 TI - Construction of Saccharomyces cerevisiae strains that accumulate relatively low concentrations of trehalose, and their application in testing the contribution of the disaccharide to stress tolerance. AB - Genetically related diploid strains of Saccharomyces cerevisiae that accumulate varied amounts of trehalose during starvation for nitrogen have been constructed. Strains that produced greater than 5% trehalose (dry cell weight) were more tolerant of thermal, or freeze-thaw stresses than strains that produced less than 4% trehalose. Thus trehalose appears to play a role in stress tolerance of yeast. The significance of these results is that, for the first time, a series of related, unmutated strains have been used to test the effect of trehalose on thermotolerance. Previous studies employed either heat shock treatment, or mutated strains to provide trehalose variations, and as such the contribution of the disaccharide to stress tolerance could not necessarily be separated from other factors such as heat shock proteins. PMID- 1426992 TI - Denitrification by fungi. AB - Many fungi in the centre of the group of Fusarium and its teleomorphs were shown to be capable of reducing nitrite anaerobically to form nitric oxide (NO), nitrous oxide (N2O), and/or dinitrogen (N2). Several strains could reduce nitrate as well. Nitrous oxide was the major product of the reduction of nitrate or nitrite. Several fungi could also form N2. When [15]nitrite was used as substrate for the N2-forming denitrification, 15N2O, 15NO, and 14N15N were obtained as the products. These results demonstrated that, unexpectedly, many fungi have denitrifying abilities. It was also shown that the fungal system contains a unique reaction, formation of a hybrid dinitrogen. PMID- 1426993 TI - Identification of 27-oxo-octacosanoic acid and heptacosane-1,27-dioic acid in Legionella pneumophila. AB - Two long-chain fatty acids, 27-oxo-octacosanoic acid (28:0(27-oxo)) and heptacosane-1,27-dioic acid (27:0-dioic) were identified for the first time in phenol-chloroform-petroleum ether extracts of Legionella pneumophila, indicating that they are constituents of lipopolysaccharide. The fatty acids were characterised by combined gas-liquid chromatography/mass spectrometry and proton nuclear magnetic resonance spectroscopy. Moreover, minor amounts of 29-oxo triacontanoic (30:0(29-oxo)) acid and nonacosane-1,29-dioic acid (29:0-dioic) as well as 27-hydroxy-octacosanoic acid (28:0(27-OH)) were present in the phenol chloroform-petroleum ether extract. PMID- 1426994 TI - Affinity for porcine respiratory tract mucus is found in some isolates of Actinobacillus pleuropneumoniae. AB - The ability of 17 Actinobacillus pleuropneumoniae isolates representing serotypes 1, 2, 5, and 7, to adhere in vitro to porcine respiratory tract mucus was examined. Adherence of bacteria to crude mucus preparations was evaluated by use of a dot-blot assay and an enzyme immunoassay. Seventy per cent (12/17) of the isolates of A. pleuropneumoniae had affinity, to various degrees, for porcine respiratory tract mucus. No relationship was found between affinity for respiratory mucus and serotype, haemagglutination, lipopolysaccharide (LPS) profiles, or adherence to porcine tracheal rings. However, a correlation was found between affinity for respiratory mucus and capsular material thickness; heavily encapsulated isolated showed no or less affinity for mucus than isolates with a thinner layer of capsular material. Moreover, two encapsulated isolates showed less affinity for mucus than their acapsulated variant. Finally, the affinity of A. pleuropneumoniae for respiratory mucus was heat- and proteinase-K resistant. Our data suggest that capsular material of A. pleuropneumoniae could mask a surface component, possibly LPS, which has affinity for porcine respiratory mucus. PMID- 1426995 TI - Characterization of killer-resistant strains of Saccharomyces cerevisiae isolated from spontaneous fermentations. AB - A study of 26 killer-resistant wine strains of Saccharomyces cerevisiae, isolated during spontaneous fermentations in three vineyards in NW Spain, was carried out employing several methods that included a spheroplast-killing assay and analysis of chromosomal DNA patterns by pulse-field agarose electrophoresis. The results showed that 92% of the strains were derivatives of K2 killer toxin producing wine strains isolated from the same fermentations, and that they could be grouped into four different karyotypes. The remaining strains were killer-resistant at cell wall level and were not related to the others, as was demonstrated by the absence of L and M ds-RNAs and by their different karyotypes. PMID- 1426996 TI - Anthranilic acid release in adenosine-inhibited cultures of Saccharomyces cerevisiae and its inhibition by thiamin. AB - Adenosine, at 1 mM concentrations or above, was found to have a fungistatic effect on Saccharomyces cerevisiae. A substance with amethyst fluorescence was detected in the medium of adenosine-inhibited cultures of S. cerevisiae. This compound was isolated and physicochemically identified as anthranilic acid. Both the inhibition of growth and release of anthranilic acid induced by adenosine were abrogated by thiamin or by the pyrimidine portion of thiamin, 2-methyl-4 amino-5-hdroxymethyl-pyrimidine (hydroxymethyl-pyrimidine); the latter was found to restore intracellular thiamin content that had been reduced by adenosine. It was demonstrated that effects of thiamin and hydroxymethylpyrimidine on S. cerevisiae cultured with adenosine resulted from their inhibition of adenosine uptake by growing yeast cells. PMID- 1426997 TI - Cloning and sequencing of a plasmid-mediated erythromycin resistance determinant from Staphylococcus xylosus. AB - A 2.3-kb DNA fragment cloned from plasmid pCH200, the largest (52 kb) of four plasmids detected in Staphylococcus xylosus, was found to confer resistance to 14 membered ring macrolides in Bacillus subtilis and Staphylococcus aureus. DNA sequence analysis of the fragment revealed the presence of an open-reading frame, the deduced product of which was identical to one of the two ATP-binding domains encoded by the macrolide/streptogramin-B-resistance gene msrA of Staphylococcus epidermidis. The observation that a polypeptide homologous to the C-terminus of MsrA is capable of mediating erythromycin resistance in the absence of the N terminal region is of significance both to the evolution and functional activity of members of the ATP-binding transport super-gene family. PMID- 1426998 TI - Purification and characterization of two extracellular beta-glucosidases from Aspergillus nidulans. AB - Two beta-glucosidases, P-I and P-II, were purified from the culture filtrate of Aspergillus nidulans. The M(r) values of P-I and P-II were about 125,000 and 50,000, respectively. The isoelectric point, optimal pH and temperature, Michaelis constants for several substrates and inhibition constants for glucose and glucono-delta-lactone of each enzyme were determined. We conclude that the high affinity toward cellobiose and low inhibition by glucose of these enzymes may offer significant advantages in improving cellulose hydrolysis. PMID- 1426999 TI - Specificity of monoclonal antibodies binding to the polysaccharide antigens (Vi, O9) of Salmonella typhi. AB - A panel of monoclonal antibodies were generated against the surface polysaccharide antigens of the cell envelope of Salmonella typhi. Four clones (IgM) were specific for the capsular Vi polysaccharide, and one clone (IgG3) reacted selectively with the S. typhi lipopolysaccharide in enzyme immunoassay. On the basis of their reactivity pattern and binding affinity, MATy-V7 (IgM) and MATy-O9 (IgG3) antibodies were selected for further characterization of their antigenic specificity. In an inhibition enzyme immunoassay with rabbit factor specific anti-Salmonella antibodies as the competing agents, the reactivity of MATy-V7 and MATy-O9 were significantly inhibited by the anti-Vi and anti-O9 antisera, respectively. Moreover, both the Vi- and O9-specific monoclonal antibodies were shown to be useful serotyping agents by correct identification in slide agglutination tests of 32 clinical isolates of all the S. typhi and other serogroup D salmonellae among a total of 140 bacterial isolates representing eight different Enterobacteriaceae genera tested. PMID- 1427000 TI - Histidine aminotransferase activity in Streptomyces tendae and its correlation with nikkomycin production. AB - Streptomyces tendae Tu901 produces nikkomycins belonging to the nucleoside peptide antibiotics. Mutants defective in histidine catabolism were isolated and characterized with regard to their histidine ammonium-lyase activity and antibiotic synthesis. In the histidine ammonialyase-negative mutant hut-11 which was unimpaired in nikkomycin production histidine aminotransferase activity was detected as an additional histidine metabolizing enzyme. A protein exhibiting histidine aminotransferase activity could be demonstrated on non-denaturing gels of hut-11 crude extracts. Using optimized assay conditions, histidine aminotransferase activity was investigated in the strain hut-11 during growth in nikkomycin production medium. Maximal activity was reached at the end of exponential growth prior to nikkomycin production. In the presence of bromopyruvate, an effective inhibitor of histidine aminotransferase activity in vitro, production of nikkomycin Z and X was markedly reduced in hut-11. PMID- 1427001 TI - Maltose uptake and its regulation in Bacillus subtilis. AB - Extracts prepared from cultures of Bacillus subtilis, grown on maltose as the sole carbon source, lacked maltose phosphotransferase system activity. There was, however, evidence for a maltose phosphorylase activity, and such extracts also possessed both glucokinase and glucose phosphotransferase system activities. Maltose was accumulated by whole cells of B. subtilis by an energy-dependent mechanism. This uptake was sensitive to the effects of uncouplers, suggesting a role for the proton-motive force in maltose transport. Accumulation of maltose was inhibited in the presence of glucose, and there was no accumulation of maltose by a strain carrying the ptsI6 null-mutation. A strain carrying the temperature-sensitive ptsI1 mutation accumulated maltose normally at 37 degrees C but, in contrast to the wild-type, was devoid of maltose transport activity at 47 degrees C. The results indicate a role for the phosphotransferase system in the regulation of maltose transport activity in this organism. PMID- 1427002 TI - In vivo recombination and the production of hybrid genes. AB - In vivo recombination between homologous genes is increasingly being favoured as a means of generating proteins with altered and novel specificities. The typical procedure requires the cloning of two related genes on a single replicative plasmid of Escherichia coli and the selection or screening of recombinants. Up to now the recombination process between the cloned genes was generally thought to involve the recA function and the availability of free ends in the DNA molecule to be recombined. Our results show that neither is necessary. Recombinants are obtained by simply growing the bacteria that host the plasmid carrying the two cloned genes. PMID- 1427003 TI - Gentisate pathway in Salmonella typhimurium: metabolism of m-hydroxybenzoate and gentisate. AB - Salmonella typhimurium was shown to use the gentisate pathway to metabolize m hydroxybenzoate and gentisate, m-Hydroxybenzoate hydroxylase and gentisate 1,2 dioxygenase were induced by growth on either gentisate or m-hydroxybenzoate. These enzymes were not detected when the bacteria were grown with glucose or glucose and either m-hydroxybenzoate or gentisate. However, both enzymes were induced when the bacteria were grown on succinate with either substrate. The maleylpyruvate isomerase required reduced glutathione and was irreversibly inhibited by N-ethylmaleimide. PMID- 1427004 TI - Prevalence of ompT among Escherichia coli isolates of human origin. AB - OmpT is a protease associated with the outer membrane of Escherichia coli and possesses a high degree of homology to the plasminogen activator, Pla, of Yersinia pestis. We show here that OmpT from intact cells can indeed activate plasminogen. Clinical specimens of E. coli were examined for protease activity and for the ompT gene. Few isolates (12%) were found to be positive for OmpT activity, whereas most (77%) carried the ompT gene and expressed the cloned protease gene. In this report we present evidence suggesting that the surface architecture of E. coli influences the activity of OmpT and that OmpT may be indicative of the pathogenic potential of the organism. PMID- 1427005 TI - The polymerase chain reaction: an epidemiological tool to differentiate between two clusters of pathogenic Yersinia enterocolitica strains. AB - A primer set designed to amplify the enterotoxin (yst) gene of pathogenic Yersinia enterocolitica strains generated two different electrophoretic profiles of the target sequence when a collection of strains of worldwide origin was screened. Serovars O:1,3; O:2a,3; O:3; O:5,27 and O:9, known as European strains, produced a 200-bp fragment that matched the size of the target sequence. However, serovars O:4,32; O:8; O:13a,13b; O:20 and O:21, known as American strains, generated two fragments of 1.4 and 1.6 kb. The amplified products of one American strain were sequenced and the presence of the yst gene was confirmed in both fragments. Thus, the potential of the polymerase chain reaction to be used as an epidemiological tool in differentiation between the two clusters of pathogenic strains of Y. enterocolitica could be demonstrated. PMID- 1427006 TI - Antitubercular activity of trifluoperazine, a calmodulin antagonist. AB - Trifluoperazine, a calmodulin antagonist, completely inhibited the growth of mycobacteria. The minimum inhibitory concentrations in shake cultures in a synthetic medium containing 0.2% Tween 80 were 5 and 8 micrograms/ml, respectively, for the human pathogenic strain Mycobacterium tuberculosis H37Rv and M. tuberculosis resistant to isoniazid. When added to a growing culture of M. tuberculosis H37Rv on the 10th day (mid exponential phase), trifluoperazine 50 micrograms/ml further arrested growth of this organism. It is suggested that trifluoperazine or similar calmodulin antagonists might be useful as antitubercular drugs. PMID- 1427007 TI - Comparison of the nucleotide sequence and development of a PCR test for the epsilon toxin gene of Clostridium perfringens type B and type D. AB - The sequence of the epsilon toxin gene of Clostridium perfringens type D was determined and compared with that of the previously reported type B sequence. It showed two nucleotide changes in the open reading frame, giving rise to one amino acid substitution. The promoter sequences were not homologous, and different putative -35 and -10 regions have been identified in each. The sequence information was used to develop PCR primers which were specific for the epsilon toxin gene. The utility of this system for identifying type B or D strains of C. perfringens was demonstrated. PMID- 1427008 TI - The inhibition of fungal cellulolysis by cell-free preparations from ruminococci. AB - The degradation of filter paper by the anaerobic fungus Neocallimastix frontalis strain RE1 was reduced by the addition of cell-free supernates from cultures of Ruminococcus albus strain J6 and R. flavefaciens strains 17 and 007. Fungal uptake of, and growth on, glucose was not affected. After gel permeation and anion exchange chromatography, inhibitory activity towards fungal cellulolysis was recovered in a fraction from strain 17 that contained at least five negatively charged polypeptide components, molecular mass 45-68 kDa, on SDS-PAGE. PMID- 1427009 TI - Mercuric reductase in environmental gram-positive bacteria sensitive to mercury. AB - According to existing data, mercury resistance operons (mer operons) are in general thought to be rare in bacteria, other than those from mercury contaminated sites. We have found that a high proportion of strains in environmental isolates of Gram-positive bacteria express mercuric reductase (MerA protein): the majority of these strains are apparently sensitive to mercury. The expression of MerA was also inducible in all cases. These results imply the presence of phenotypically cryptic mer resistance operons, with both the merA (mercuric reductase) and merR (regulatory) genes still present, but the possible absence of the transport function required to complete the resistance mechanism. This indicates that mer operons or parts thereof are more widely spread in nature than is suggested by the frequency of mercury-resistant bacteria. PMID- 1427010 TI - Development and evaluation of a rapid, simple, sensitive, monoclonal antibody based co-agglutination test for direct detection of Vibrio cholerae 01. AB - Cholera epidemics caused by Vibrio cholerae 01 continue to represent a major public health concern in many developing countries. A rapid and simple test kit for the detection of V. cholerae 01 has been developed. The kit, CholeraScreen is a monoclonal antibody-based, co-agglutination test and is used directly with stool specimens. It does not include culturing the specimen and is performed without the need for sophisticated laboratory equipment. Specificity of the test was demonstrated, using 118 reference cultures, to which cross-reactions were not observed. Preliminary results of field trials carried out in Guatemala and Bangladesh demonstrated that the test is equally sensitive as conventional culture methods in detecting V. cholerae and, in many cases, more sensitive. The CholeraScreen test is simple, specific, and does not require culturing procedures, making it suitable for direct detection of cells of V. cholerae in clinical specimens, even in the field. Also, the test requires less than five minutes to complete. PMID- 1427011 TI - Fosfomycin enhances the expression of penicillin-binding protein 2 in methicillin sensitive and methicillin-resistant Staphylococcus aureus strains. AB - The effects of fosfomycin on penicillin-binding proteins (PBPs) were studied on the methicillin-resistant Staphylococcus aureus strain CIP (Collection de l'Institut Pasteur, Paris, France) 65-25 and on a methicillin-susceptible S. aureus strain CIP 65-6. The combinations of fosfomycin and oxacillin were synergistic, additive or antagonistic, depending on antibiotic concentrations. Fosfomycin induced modifications of the PBP profile of the two strains studied. In particular, it increased the expression of PBP2. This suggested that this protein is inducible; the only PBP not affected by fosfomycin was PBP3. PMID- 1427012 TI - Identification of a lipoamide dehydrogenase gene as second locus affected in poly(3-hydroxybutyric acid)-leaky mutants of Alcaligenes eutrophus. AB - From a genomic library of Alcaligenes eutrophus strain H16 in the broad-host range cosmid pVK100 a 6300-bp EcoRI-fragment was cloned, which restored the wild type phenotype in transposon-induced poly(3-hydroxybutyric acid)-leaky mutants, derived from A. eutrophus. Nucleotide sequence analysis of the region adjacent to the transposon insertion revealed an open reading frame which complied with all criteria for a coding region. This region was referred to as phbL, and the deduced amino acid sequence from this part of phbL showed 60% amino acid identity in an overlap of 98 residues to the lipoamide dehydrogenase gene (lpd) of Escherichia coli. In addition, the 6300-bp EcoRI-fragment conferred expression of lipoamide dehydrogenase activity to E. coli. PMID- 1427013 TI - Conjugative trimethoprim resistance in Staphylococcus aureus. AB - A multiply resistant Staphylococcus aureus isolate, WBG7410, harbours plasmids of 38, 26, 2.8, 2.4 and 1.9 kb and transfers trimethoprim and kanamycin resistance at high frequencies by conjugation. The transconjugants contained the 38-kb plasmid, pWBG707, and the 2.8-kb plasmid. Plasmid pWBG707 was shown to encode trimethoprim resistance, was conjugative and mobilised at high frequencies the 2.8-kb plasmid which presumably encodes kanamycin resistance. Plasmid pWBG707 was isolated mostly in the open circular form and analysis with EcoRI restriction endonuclease suggests that pWBG707 is a new conjugative plasmid distinct from the other conjugative plasmids reported in S. aureus. PMID- 1427014 TI - Eight bacterial proteins, including UDP-N-acetylglucosamine acyltransferase (LpxA) and three other transferases of Escherichia coli, consist of a six-residue periodicity theme. AB - Only a few prokaryotic or eukaryotic enzymes are known to consist of a tandem repeat structure. This report describes a common hexapeptide-repeat theme in four Escherichia coli transferases and in four less-characterized bacterial proteins. The proteins are the Ssc protein of Salmonella typhimurium (25), UDP-N acetylglucosamine acyltransferase of E. coli (24), the hypothetical proteins Tms of Bacillus subtilis (23) and Yglm of E. coli (22), succinyldiaminopimelate aminotransferase of E. coli (14), serine acetyltransferase of E. coli (13), NodL of Rhizobium leguminasorum (13), and thiogalactoside acetyltransferase of E. coli (8) (number of repeats indicated in parentheses). In UDP-N-acetylglucosamine acyltransferase, the repeats constitute 55% of the total protein. Each hexapeptide repeat of the eight proteins starts with Ile, Leu, or Val. Position b is occupied by Gly, position d by Gly, Asn, or Asp, and position e by Val or Ala in 52%, 54%, and 56% of the hexapeptide repeats, respectively. PMID- 1427015 TI - Chitin synthetase activity is bound to the plasma membrane and to a cytoplasmic particulate fraction in Candida albicans germ tube cells. AB - Subcellular distribution of chitin synthetase has been studied in germ tubes of Candida albicans. Two fractions with synthetase activity were separated from cell homogenates: (i) a mixed membrane fraction where the enzyme, partly in an active form, is associated with the plasma membrane (isopycnic centrifugation of mixed membrane fraction on linear sucrose gradients resolved a unique peak of activity matching with [3H]ConA-labelled membranes at a buoyant density of 1.195 g/ml); and (ii) a cytoplasmic fraction containing fully zymogenic enzyme associated with particles whose buoyant density (determined by isopycnic centrifugation on linear sucrose gradients) depended on the cell breakage conditions. The actual cytoplasmic fraction-enzyme may correspond to particles with buoyant density 1.135 g/ml (chitosomes), whereas the enzyme particles with other densities (1.085 and 1.165 g/ml) probably originated during cell disruption, as has been reported previously to occur during the preparation of yeast cell homogenates. PMID- 1427016 TI - Characterization of isofunctional ring-cleaving enzymes in aniline and 3 chloroaniline degradation by Pseudomonas acidovorans CA28. AB - During degradation of aniline and 3-chloroaniline, respectively, by Pseudomonas acidovorans CA28, selective induction of two catechol 1,2-dioxygenases (C12O) was observed. C12O I activity was the sole ring-cleaving enzyme detectable in cell free extracts after growth on aniline, while C12O II was exclusively found after growth on 3-chloroaniline. Both enzymes were clearly differentiated by their elution behaviour on DEAE-cellulose and their substrate specificities. For C12O I high activity was demonstrable only with unsubstituted catechol, while C12O II showed preference for and high affinity towards chlorinated catechols. Therefore, evidence of different ortho-cleavage enzymes in Pseudomonas acidovorans CA28 involved in aniline and 3-chloroaniline metabolism, respectively, is indicated. PMID- 1427018 TI - Characterization of the common antigenic lipopolysaccharide O-chains produced by Bordetella bronchiseptica and Bordetella parapertussis. AB - Representative strains of Bordetella bronchiseptica and B. parapertussis were found to produce smooth lipopolysaccharides (LPS) having identical antigenic O polysaccharide components composed of linear unbranched polymers of 1,4-linked 2,3-diacetamido-2,3-dideoxy-alpha-L-galacto-pyranosyluronic acid residues. These LPSs differed from the LPS of B. pertussis which produces only rough-type LPS, devoid of O-polysaccharide. While B. bronchiseptica and B. parapertussis had chemically and immunologically identical O-polysaccharide structures, their core oligosaccharide components differed. The core oligosaccharide of B. parapertussis was chemically distinct from the core of B. bronchiseptica which appeared to be structurally and immunologically similar to a core oligosaccharide of B. pertussis. PMID- 1427017 TI - Analysis of two gene regions involved in the expression of the imipenem-specific, outer membrane porin protein OprD of Pseudomonas aeruginosa. AB - A Tn501 mutant of Pseudomonas aeruginosa resistant to imipenem and lacking the imipenem-specific outer membrane porin protein OprD was isolated. The mutation could be complemented to imipenem susceptibility and OprD-sufficiency by a cloned 6-kb EcoRI-PstI fragment of DNA from the region of chromosome of the wild-type strain surrounding the site of Tn501 insertion. However, this fragment did not contain the oprD structural gene as judged by its inability to hybridize with an oligonucleotide corresponding to the N-terminal amino acid sequence of OprD. DNA sequencing of 3.9 kb of the region surrounding the Tn501 insertion site revealed three large open reading frames, one of which would be interrupted by the Tn501 insertion in the mutant. This latter open reading frame, named opdE (for putative regulator of oprD expression), predicted a hydrophobic protein of M(r) 41,592. Using the above-mentioned oligonucleotide, the oprD structural gene was cloned and expressed in Escherichia coli on a 2.1-kb Bam HI-KpnI fragment. DNA sequencing predicted a 420 amino acid mature OprD protein with a 23 amino acid signal sequence. PMID- 1427019 TI - Segregation analysis of 159 soft tissue sarcoma kindreds: comparison of fixed and sequential sampling schemes. AB - In this study we compared parameter estimates and model hypotheses in pedigree data collected by fixed sampling with estimates and hypotheses derived by sequential sampling. Employing a fixed sampling scheme, we previously analyzed data on relatives of 159 childhood sarcoma patients. We have now extracted from that data set individuals who would have been included in a sequentially sampled study. We applied segregation analysis to the truncated data, to determine the mode of inheritance and major locus parameter estimates. With data from both sampling schemes we made a family-by-family comparison to determine each family's contribution to a major gene model. The two sampling schemes yielded similar results: we detected segregation of a dominant major gene and obtained similar major locus parameter estimates. However, the sequential sampling scheme derived these conclusions from data on 982 relatives rather than the 2,451 ascertained in the fixed sampling scheme. The sequential sampling scheme failed to identify only one of the kindreds likely to be segregating the gene. For this data set, the sequential sampling scheme would have provided an efficient mechanism to discriminate genetic hypotheses and would have permitted focus of resources on the specific kindreds likely to segregate a major gene. PMID- 1427020 TI - Two common polymorphisms in the APO A-IV coding gene: their evolution and linkage disequilibrium. AB - Human apolipoprotein A-IV (APO A-IV) exhibits a common protein polymorphism detectable by isoelectric focusing (IEF) due to a single base substitution at codon 360 which replaces the frequently occurring glutamine residue (allele 1) with histidine (allele 2). Recently, sequence analysis of the APO A-IV coding region has revealed another common nucleotide substitution at codon 347 which converts the commonly present threonine residue (allele A) into serine (allele T). In order to investigate the extent of genetic variation at codon 347, we screened DNA samples from 192 unrelated individuals using a polymerase chain reaction based assay. The frequencies of the two alleles, A-IV*A and A-IV*T, were 0.81 and 0.19, respectively, with average heterozygosity 0.31. Genetic screening of the corresponding 192 plasma samples by IEF gave frequencies of 0.922 and 0.078 for the A-IV*1 and A-IV*2 alleles, respectively, at codon 360 with average heterozygosity 0.14. Genotype data at the two polymorphic sites were used to assign unequivocal haplotypes to all the 384 chromosomes. Of the expected four haplotypes (A1, T1, A2, and T2) only three were observed and their frequencies were 0.732 for A1, 0.190 for T1 and 0.078 for A2, with average heterozygosity 0.42. Although our data indicate significant linkage disequilibrium between the two sites (chi 21 = 7.65, P < 0.006, standardized disequilibrium constant phi = 0.14) the degree of nonrandom association varied between alleles at the two sites. Based upon allele frequency data and variable linkage disequilibrium between alleles, we propose that the A2 and T1 haplotypes may have evolved from the parental A1 haplotype by two independent mutations. PMID- 1427021 TI - Family study of alpha 1-antitrypsin deficiency: effects of cigarette smoking, measured genotype, and their interaction on pulmonary function and biochemical traits. AB - To gain insight into the variable expression of lung disease in alpha 1 antitrypsin (alpha 1AT) deficiency, five quantitative variables including forced expiratory volume at 1 sec (FEV1), forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25-75), total serum alpha 1AT, oxidized serum alpha 1AT, and total serum immunoglobulin E (IgE) were measured in alpha 1AT deficient individuals and their families. The effect of a known, measured genotype (the Pi type) was estimated for each quantitative trait; the influence of mode of case ascertainment on the measured genotype effect was also assessed. These analyses showed that total alpha 1AT levels are strongly influenced by Pi type; IgE levels are unaffected by Pi type; and FEV1, FEF25-75, and oxidized alpha 1AT are moderately influenced by Pi type. The effect of genotype-by-environment interaction between Pi type and pack-years of cigarette smoking on the five quantitative phenotypes was studied using an analysis of covariance. Significant Pi x pack-years interaction was evident for FEV1, but this effect is confounded in this data set with the Pi x age interaction. Probands who were ascertained because they had chronic obstructive pulmonary disease (COPD) do not demonstrate the significant Pi x pack-years interaction effect of the Pi x pack-years subjects ascertained for other reasons demonstrate. The effect of the Pi x pack years interaction on FEV1 was no longer significant on a transformed scale, (FEVf12,) thus providing an additive scale for future data analysis. The increased sensitivity of Pi MZ individuals in our sample to cigarette smoking reduced the Pi x packs-years interaction effect on FEF25-75 to borderline significance. This investigation has provided an opportunity to incorporate both measured genotype and genotype-by-environment interaction analyses into the study of the variable expression of lung disease in Pi Z individuals. PMID- 1427022 TI - Commingling analysis of memory performance in offspring of Alzheimer patients. AB - Dementia of the Alzheimer type (DAT) is a neurodegenerative disorder which afflicts approximately 3% of the population. Genetic influences are indicated from twin and family studies although genetic heterogeneity has been suggested from both pedigree analyses and linkage investigations. Autosomal dominant inheritance with age-dependent penetrance has been suggested in at least some families with DAT. In the present investigation, we examine memory and nonmemory task performance in 106 asymptomatic offspring (mean age 40.6 years) of 54 DAT probands. Intraclass sibling correlations revealed little evidence of sibling similarity for performance on three memory tasks which have been reported to be relatively sensitive to the memory losses accompanying DAT. Subsequent investigations of the distributions of the cognitive task scores in the offspring revealed evidence for a commingling of two distributions for the three memory tasks but not for the nonmemory measures. These findings are consistent with a hypothesis that these distributions reflect genotypic subgroups, carriers, and noncarriers, of a presumed DAT gene. PMID- 1427023 TI - Two-locus models of disease. AB - Most complex diseases have not been amenable to genetic analysis under the assumption of single locus or multifactorial models. Consequently, interest has turned to the consideration of the properties of oligogenic models. i.e., genetic models involving a small number of genes. Nine two-locus models of disease, representing both epistatic and heterogeneous genetic models, are investigated: three models of heterogeneity and six models of epistatis. For each model we derive formulas for the recurrence risk to various classes of relatives in terms of penetrances and gene frequencies. We also develop formulas for the components of variance for the epistatic models in terms of the same genetic parameters. The range of penetrances and the associated gene frequencies that predict a predetermined value for the population prevalence and recurrence risk to the sibling of proband are calculated for various rates of the prevalence and risk to sibs. It is found that for many of these genetic models, there is a very limited range of penetrances that fit a particular set of assumed risks. Estimated population prevalence and risks to sibs and monozygotic twins for bipolar and schizophrenia illness are used to test for compatibility with expected values for recurrence risks under these models. PMID- 1427024 TI - Preliminary ordering of multiple linked loci using pairwise linkage data. AB - A method is presented for the preliminary ordering of loci on a chromosome using pairwise linkage data. The method is based on the biologically reasonable assumption that the "true" order of a set of linked loci will be the one that minimizes the total length of the chromosome segment. Here the "length" is defined as the sum of adjacent recombination fractions. The method searches for the optimal order, represented by a minimum distance map (MDMAP), even when it is not possible to examine the n!/2 possible distinct orders for n loci. A computerized approach, using the simulated annealing algorithm of Kirkpatrick et al. [1983], forms the basis of the method. It can be applied to data from radiation hybrid experiments as well as that from conventional family linkage studies. The technique is applied to several sets of published data to illustrate how it performs in practice. The advantages and the disadvantages of the method are discussed so that it will be clear under what conditions it is likely to work well. When data sets are "complete," in the sense that all possible pairwise recombination fractions have estimates, and when no large clusters of extremely tightly linked loci are present, the method produces ordered sets of loci that agree well with those generated by other, more complex methods. Any discrepancies that occur are likely to be with respect to the orientation of nearest-neighbor loci, where relative order cannot be reliably established by any method. The method thus provides a simple, rapid means of obtaining a preliminary order for a set of loci known to be in the same linkage group. PMID- 1427025 TI - Development of inquiry behavior in concept identification. AB - We studied inquiry behavior in concept identification in first-, fifth-, eighth grade, and college students with problems involving eight four-letter strings. The task was to identify the correct string by asking questions related to either one letter or four letters that were answered by yes or no. Processing demands were manipulated by comparing (a) a condition in which letter strings were removed from view as feedback eliminated them as possible solutions with a condition in which strings remained in view and (b) problems that were structured so that relevant letter categories were easy to identify with problems that were not. Problem solving generally improved with age. First graders tended to ask questions that eliminated solutions one by one, whereas the older groups asked more informative questions. At the three upper grade levels, strategies for selecting queries were adapted to situations, with less demanding strategies being used when processing demands were higher. PMID- 1427026 TI - The influence of a child's disability on mother's role functioning and psychological well-being. AB - We assessed the influences of specific characteristics of a child with a disability on a mother's role functioning and psychological well-being in 112 mother-child dyads. Children were teenagers and young adults (aged 13-26) with chronically disabling conditions enrolled in day treatment programs; mothers ranged in age from 33 to 68 years. Semi-structured interviews were conducted with the mothers regarding their psychological and social functioning. Information regarding the children's disabling condition was available from their treatment centers. Results of a path analysis indicated that various aspects of a disabled child's condition indirectly affected mother's psychological functioning via a direct effect on mother's role functioning. Intervention efforts could be targeted toward mother's role functioning and specific child characteristics (i.e., physical limitations and emotional/behavioral adjustment). PMID- 1427027 TI - Posttraumatic stress disorder: a review. AB - In this article, I have reviewed posttraumatic stress disorder with Vietnam veterans, soldiers in other wars, and in victims of natural and civilian disasters. A discussion of measurement and therapy approaches is included. PMID- 1427028 TI - Forty years ago: the discovery of bacterial transduction. PMID- 1427029 TI - DNA inversions between short inverted repeats in Escherichia coli. AB - Using site-specific mutagenesis in vitro, we have constructed Escherichia coli strains that allow the detection of the inversion of an 800-bp segment in the lac region. The invertible segment is bounded by inverted repeats of either 12 or 23 bp. Inversions occurring at these inverted repeats will restore the Lac+ phenotype. Inversions can be detected at both short homologies at frequencies ranging from 0.5 x 10(-8) to 1 x 10(-7). These events, which have been verified by DNA sequence analysis, are reduced up to 1000-fold in strains deficient for either RecA, RecB or RecC. They are not reduced in strains deficient in the RecF, J pathway. These results show that the RecB,C,D system can mediate rearrangements at short sequence repeats, and probably plays a major role in cellular rearrangements. PMID- 1427030 TI - Sequence analysis of mutations arising during prolonged starvation of Salmonella typhimurium. AB - We have examined the effects of prolonged histidine deprivation on the reversion of Salmonella typhimurium histidine auxotrophs containing either hisG46, a missense mutation (CTC----CCC), or hisG428, an ochre mutation (CAA----TAA). Both of these mutants can revert to His+ via intragenic and extragenic mechanisms. Whereas the hisG46 mutant site consists of G/C base pairs, extragenic suppression of hisG46 requires mutation at an A/T site. Conversely, the hisG428 site itself contains only A/T base pairs, and extragenic suppression of hisG428 occurs principally at G/C sites. Thus, by examining the mutational spectrum of hisG46 and hisG428 revertants that occurred in the presence and in the absence of histidine, it was possible to determine the effects of histidine starvation on mutations at G/C vs. A/T sites as well as on intragenic sites vs. extragenic suppressor sites. Using DNA-colony hybridization, we determined the DNA sequences of over 1300 hisG46 and hisG428 revertants. Histidine-independent revertants that arose during growth in liquid medium that contained histidine included both intragenic and extragenic suppressor mutations. The relative frequency of such extragenic suppressors was greatly reduced among the His+ revertants that were isolated after 5-10 days of histidine starvation on agar medium. Moreover, DNA sequence analysis revealed striking differences in the distribution of particular transversions at the hisG428 locus in revertants arising after prolonged histidine starvation as compared to those arising after growth in the presence of histidine. PMID- 1427031 TI - The relapsing fever agent Borrelia hermsii has multiple copies of its chromosome and linear plasmids. AB - Borrelia hermsii, a spirochete which causes relapsing fever in humans and other mammals, eludes the immune response by antigenic variation of the "Vmp" proteins. This occurs by replacement of an expressed vmp gene with a copy of a silent vmp gene. Silent and expressed vmp genes are located on separate linear plasmids. To further characterize vmp recombination, copy numbers were determined for two linear plasmids and for the 1-megabase chromosome by comparing hybridization of probes to native DNA with hybridization to recombinant plasmids containing borrelial DNA. Plasmid copy numbers were also estimated by ethidium bromide fluorescence. Total cellular DNA content was determined by spectrophotometry. For borrelias grown in mice, copy numbers and 95% confidence intervals were 14 (12 17) for an expression plasmid, 8 (7-9) for a silent plasmid, and 16 (13-18) for the chromosome. Borrelias grown in broth medium had one-fourth to one-half this number of plasmids and chromosomes. Staining of cells with 4',6-diamidino-2 phenylindole revealed DNA to be distributed throughout most of the spirochete's length. These findings indicate that borrelias organize their total cellular DNA into several complete genomes and that cells undergoing serotype switches do one or more of the following: (1) coexpress Vmps from switched and unswitched expression plasmids for at least three to five generations, (2) suppress transcription from some expression plasmid copies, or (3) partition expression plasmids nonrandomly. The lower copy number of the silent plasmid indicates that nonreciprocal Vmp gene recombination may result from loss of recombinant silent plasmids by segregation. PMID- 1427032 TI - Systematic mutational analysis of the yeast ACT1 gene. AB - We report the isolation and characterization of a synoptic set of site-directed mutations distributed throughout the single actin gene of Saccharomyces cerevisiae. Mutations were systematically targeted to the surface of the protein by identifying clusters of 2 or more charged residues in the primary sequence; every charged residue in a cluster was replaced with alanine. Mutations were recovered in high yield (34 of 36 constructed) as heterozygous diploids. Mutant phenotypes were examined in haploid segregants: 11 were recessive lethal, 16 conditional-lethal (including temperature-sensitive and salt-sensitive) and 7 had no discernible phenotype. Genetic analysis suggested that the two mutations constructed but not recovered in yeast may have a dominant defective phenotype. Location of the mutant residues on the three-dimensional structure of the rabbit muscle actin monomer confirmed that most (81%) of the charged residues we altered lie at or near the surface of the protein, confirming a key assumption of the method. Many of the new act1 alleles have properties readily interpreted in light of the actin structure and should prove useful in both genetic and biochemical studies of actin function. PMID- 1427033 TI - Identification and characterization of three genes that affect expression of ADH2 in Saccharomyces cerevisiae. AB - Using a new selection protocol we have identified and preliminarily characterized three new loci (ADR7, ADR8 and ADR9) which affect ADH2 (alcohol dehydrogenase isozyme II) expression. Mutants were selected which activate ADH2 expression in the presence of an over-expressed, normally inactive ADR1 allele. The mutants had very similar phenotypes with the exception that one was temperature sensitive for growth. In the absence of any ADR1 allele, the mutants allowed ADH2 to partially escape glucose repression. However, unlike wildtype strains deleted for ADR1, the mutants were able to efficiently derepress ADH2. The mutations allowed a small escape from glucose repression for secreted invertase, but had no effect on the glucose repression of isocitrate lyase or malate dehydrogenase. The mutations were shown to be nonallelic to a wide variety of previously characterized mutations, including mutations that affect other glucose-repressed enzymes. PMID- 1427034 TI - The yeast omnipotent suppressor SUP46 encodes a ribosomal protein which is a functional and structural homolog of the Escherichia coli S4 ram protein. AB - The accurate synthesis of proteins is crucial to the existence of a cell. In yeast, several genes that affect the fidelity of translation have been identified (e.g., omnipotent suppressors, antisuppressors and allosuppressors). We have found that the dominant omnipotent suppressor SUP46 encodes the yeast ribosomal protein S13. S13 is encoded by two similar genes, but only the sup46 copy of the gene is able to fully complement the recessive phenotypes of SUP46 mutations. Both copies of the S13 genes contain introns. Unlike the introns of other duplicated ribosomal protein genes which are highly diverged, the duplicated S13 genes have two nearly identical DNA sequences of 25 and 31 bp in length within their introns. The SUP46 protein has significant homology to the S4 ribosomal protein in prokaryotic-type ribosomes. S4 is encoded by one of the ram (ribosomal ambiguity) genes in Escherichia coli which are the functional equivalent of omnipotent suppressors in yeast. Thus, SUP46 and S4 demonstrate functional as well as sequence conservation between prokaryotic and eukaryotic ribosomal proteins. SUP46 and S4 are most similar in their central amino acid sequences. Interestingly, the alterations resulting from the SUP46 mutations and the segment of the S4 protein involved in binding to the 16S rRNA are within this most conserved region. PMID- 1427036 TI - A combination inversion and translocation in Neurospora crassa with inviable deficiency progeny that can be rescued in heterokaryons. AB - Chromosome rearrangement In(IL;IR)T(IL;IIIR)SLm-1, has a pericentric inversion in linkage group I associated with a reciprocal translocation between I and III. The rearrangement was identified cytologically in pairing with normal sequence chromosomes at pachynema. Rearrangement breakpoints were mapped genetically in IL, IR and IIIR by crosses with normal sequence strains and in crosses with an inversion that partially overlaps the SLm-1 inversion. When rearrangement SLm-1 is crossed to parents with normal sequence chromosomes, one class among the progeny has a small chromosome deficiency and large duplication. The ascospores containing this deficiency/duplication die either before germination or just after, when growth commences. Germ tubes of the deficiency/duplication progeny, which start to grow then stop, resemble the aborted growth of auxotrophic mutants germinated on minimal medium. Efforts to correct the deficiency with nutritional supplements were not successful. However, the defective class can be rescued by fusing the germinating hyphae of the deficiency ascospore with a complementary auxotrophic mutant to form a heterokaryon. A deficiency/duplication nucleus that is rescued in a heterokaryon can serve as a fertilizing nucleus in crosses with a normal sequence parent. One half of their progeny have the normal chromosome sequence and one half have the chromosome deficiency syndrome and die at germination. PMID- 1427035 TI - Sister chromatids are preferred over homologs as substrates for recombinational repair in Saccharomyces cerevisiae. AB - A diploid Saccharomyces cerevisiae strain was constructed in which the products of both homolog recombination and unequal sister chromatid recombination events could be selected. This strain was synchronized in G1 or in G2, irradiated with X rays to induce DNA damage, and monitored for levels of recombination. Cells irradiated in G1 were found to repair recombinogenic damage primarily by homolog recombination, whereas those irradiated in G2 repaired such damage preferentially by sister chromatid recombination. We found, as have others, that G1 diploids were much more sensitive to the lethal effects of X-ray damage than were G2 diploids, especially at higher doses of irradiation. The following possible explanations for this observation were tested: G2 cells have more potential templates for repair than G1 cells; G2 cells are protected by the RAD9-mediated delay in G2 following DNA damage; sister chromatids may share more homology than homologous chromosomes. All these possibilities were ruled out by appropriate tests. We propose that, due to a special relationship they share, sister chromatids are not only preferred over homologous chromatids as substrates for recombinational repair, but have the capacity to repair more DNA damage than do homologs. PMID- 1427037 TI - Mutations in the sup-38 gene of Caenorhabditis elegans suppress muscle-attachment defects in unc-52 mutants. AB - Mutations in the unc-52 locus of Caenorhabditis elegans have been classified into three different groups based on their complex pattern of complementation. These mutations result in progressive paralysis (class 1 mutations) or in lethality (class 2 and 3 mutations). The paralysis exhibited by animals carrying class 1 mutations is caused by disruption of the myofilaments at their points of attachment to the cell membrane in the body wall muscle cells. We have determined that mutations of this class also have an effect on the somatic gonad, and this may be due to a similar disruption in the myoepithelial sheath cells of the uterus, or in the uterine muscle cells. Mutations that suppress the body wall muscle defects of the class 1 unc-52 mutations have been isolated, and they define a new locus, sup-38. Only the muscle disorganization of the Unc-52 mutants is suppressed; the gonad abnormalities are not, and the suppressors do not rescue the lethal phenotype of the class 2 and class 3 mutations. The suppressor mutations on their own exhibit a variable degree of gonad and muscle disorganization. Putative null sup-38 mutations cause maternal-effect lethality which is rescued by a wild-type copy of the locus in the zygote. These loss-of function mutations have no effect on the body wall muscle structure. PMID- 1427038 TI - Estimates of gene flow in Drosophila pseudoobscura determined from nucleotide sequence analysis of the alcohol dehydrogenase region. AB - The genetic structure of Drosophila pseudoobscura populations was inferred from a nucleotide sequence analysis of a 3.4-kb segment of the alcohol dehydrogenase (Adh) region. A total of 99 isochromosomal strains collected from 13 populations in North and South America were used to determine if any population departed from a neutral model and to estimate levels of gene flow between populations. This study also included the nucleotide sequences from two sibling species, D. persimilis and D. miranda. We estimated the neutral mutation parameter, 4N mu, in synonymous and noncoding sites for 17 subregions of Adh in each of nine populations with sample sizes greater than three. The nucleotide diversity data in the nine populations was tested for departures from an equilibrium neutral model with two statistical tests. The Tajima and the Hudson, Kreitman, Aguade tests showed that each population fails to reject a neutral model. Tests for genetic differentiation between populations fail to show any population substructure among the North American populations of D. pseudoobscura. The nucleotide diversity data is consistent with direct and indirect measures of gene flow that show extensive dispersal between populations of D. pseudoobscura. PMID- 1427039 TI - The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells. AB - The Enhancer of split complex [E(spl)-C] of Drosophila melanogaster is located in the 96F region of the third chromosome and comprises at least seven structurally related genes, HLH-m delta, HLH-m gamma, HLH-m beta, HLH-m3, HLH-m5, HLH-m7 and E(spl). The functions of these genes are required during early neurogenesis to give neuroectodermal cells access to the epidermal pathway of development. Another gene in the 96F region, namely groucho, is also required for this process. However, groucho is not structurally related to, and appears to act independently of, the genes of the E(spl)-C; the possibility is discussed that groucho acts upstream to the E(spl)-C genes. Indirect evidence suggests that a neighboring transcription unit (m4) may also take part in the process. Of all these genes, only gro is essential; m4 is a dispensable gene, the deletion of which does not produce detectable morphogenetic abnormalities, and the genes of the E(spl)-C are to some extent redundant and can partially substitute for each other. This redundancy is probably due to the fact that the seven genes of the E(spl)-C encode highly conserved putative DNA-binding proteins of the bHLH family. The genes of the complex are interspersed among other genes which appear to be unrelated to the neuroepidermal lineage dichotomy. PMID- 1427040 TI - Seven genes of the Enhancer of split complex of Drosophila melanogaster encode helix-loop-helix proteins. AB - Enhancer of split [E(spl)] is one of the neurogenic loci of Drosophila and, as such, is required for normal segregation of neural and epidermal cell progenitors. Genetic observations indicate that the E(spl) locus is in fact a gene complex comprising a cluster of related genes and that other genes of the region are also required for normal early neurogenesis. Three of the genes of the complex were known to encode helix-loop-helix (HLH) proteins and to be transcribed in nearly identical patterns. Here, we show that four other genes in the vicinity also encode HLH proteins and, during neuroblast segregation, three of them are expressed in the same pattern. We show by germ-line transformation that these three genes are also necessary to allow epidermal development of the neuroectodermal cells. PMID- 1427041 TI - Characterization of mutant alleles of myospheroid, the gene encoding the beta subunit of the Drosophila PS integrins. AB - This paper presents the characterization of nine alleles of myospheroid, which encodes the beta PS subunit of the Drosophila PS integrins. On Southern blots, the mysXB87, mysXN101 and mysXR04 genes yield restriction digest patterns similar to that seen for wild-type chromosomes, however the mys1 and mysXG43 genes contain detectable deletions. mys1, mysXB87 and mysXG43 make little or no stable protein product, and genetically behave as strong lethal alleles. For the mysXN101 mutation, protein product is seen on immunoblots and a reduced amount of beta PS protein is seen at muscle attachment sites of embryos; this mutant protein retains some wild-type function, as revealed by complementation tests with weak alleles. Protein is also seen on immunoblots from mysXR04 embryos, and this allele behaves as an antimorph, being more deleterious in some crosses than the complete deficiency for the locus. mysts2 and mysnj42 are typically lethal in various combinations with other alleles at high temperatures only, but even at high physiological temperatures, neither appears to eliminate gene function completely. The complementation behaviors of mysts1 and mysts3 are quite unusual and suggest that these mutations involve regulatory phenomena. For mysts3, the data are most easily explained by postulating transvection effects at the locus. The results for mysts1 are less straightforward, but point to the possibility of a chromosome pairing-dependent negative interaction. PMID- 1427042 TI - Oxygen association-dissociation and stability analysis on mouse hemoglobins with mutant alpha- and beta-globins. AB - Oxygen association-dissociation and hemoglobin stability analysis were performed on mouse hemoglobins with amino acid substitutions in an alpha-globin (alpha 89, His to Leu) and a beta-globin (beta 59, Lys to Ile). The variant alpha-globin, designated chain 5m in the Hbag2 haplotype, had an high oxygen affinity and was stable. The variant beta-globin, (beta s2) of the Hbbs2 haplotype, also had an elevated oxygen affinity and in addition was moderately unstable in 19% isopropanol. Hemoglobins from the expected nine (Hbag2/Hbag2;Hbbs/Hbbs x Hbaa/Hbaa;Hbbs2/Hbbs2) F2 genotypes can be grouped into five classes of P50 values characterized by strict additivity and dependency on mutant globin gene dosage; physiologically, both globin variants gave indistinguishable effects on oxygen affinity. The hemoglobin of normal mice (Hbaa/Hbaa;Hbbs/Hbbs) had a P50 = 40 mm Hg and the hemoglobin of Hbag2/Hbag2;Hbbs2/Hbbs2 F2 mice had a P50 = 25 mm Hg (human P50 = 26 mm Hg). Peripheral blood from Hbag2/Hbag2;Hbbs/Hbbs, Hbaa/Hbaa;Hbbs2/Hbbs2 and Hbag2/Hbag2;Hbbs2/Hbbs2 mice exhibited normal hematological values except for a slightly higher hematocrit for Hbag2/Hbag2;Hbbs/Hbbs and Hbag2/Hbag2;Hbbs2/Hbbs2 mice, slightly elevated red cell counts for mice of the three mutant genotypes, and significantly lower values for the mean corpuscular volume and mean corpuscular hemoglobin for Hbag2/Hbag2;Hbbs2/Hbbs2 mice. PMID- 1427043 TI - Evolutionary consequences of DNA mismatch inhibited repair opportunity. AB - Double strand breaks (DSBs) are often repaired via homologous recombination. Recombinational repair processes are expected to be influenced by nucleotide heterozygosity through mismatch detection systems. Unrepaired DSBs have severe biological consequences and are often lethal. We show that natural selection due to inhibition of recombinational repair associated with polymorphisms could influence their molecular evolution. The main conclusions from this analysis are that, for increasing population size, mismatch detection leads to a limit on average heterozygosity of otherwise selectively neutral polymorphism, an excess of rare variants, and a slowing down of the rate of neutral molecular evolution. The first two results suggest that mismatch detection may account for the surprisingly narrow range of observed average heterozygosities, given the great variation in population size between species. PMID- 1427044 TI - Female choice and variation in the major histocompatibility complex. AB - The cause of the high genetic variability in the major histocompatibility complex (MHC) is not entirely clear. Recently, two reports suggest that female mice prefer to mate with males different from them at the MHC. A model of female choice appropriate for those observations is developed here. Female choice can in fact reduce the observed proportions of homozygotes, maintain genetic polymorphism, influence mating-type frequencies and generate gametic disequilibrium. PMID- 1427045 TI - Estimation of levels of gene flow from DNA sequence data. AB - We compare the utility of two methods for estimating the average levels of gene flow from DNA sequence data. One method is based on estimating FST from frequencies at polymorphic sites, treating each site as a separate locus. The other method is based on computing the minimum number of migration events consistent with the gene tree inferred from their sequences. We compared the performance of these two methods on data that were generated by a computer simulation program that assumed the infinite sites model of mutation and that assumed an island model of migration. We found that in general when there is no recombination, the cladistic method performed better than FST while the reverse was true for rates of recombination similar to those found in eukaryotic nuclear genes, although FST performed better for all recombination rates for very low levels of migration (Nm = 0.1). PMID- 1427046 TI - The use of simulated annealing in chromosome reconstruction experiments based on binary scoring. AB - We present a method of combinatorial optimization, simulated annealing, to order clones in a library with respect to their position along a chromosome. This ordering method relies on scoring each clone for the presence or absence of specific target sequences, thereby assigning a digital signature to each clone. Specifically, we consider the hybridization of oligonucleotide probes to a clone to constitute the signature. In that the degree of clonal overlap is reflected in the similarity of their signatures, it is possible to construct maps based on the minimization of the differences in signatures across a reconstructed chromosome. Our simulations show that with as few as 30 probes and a clonal density of 4.5 genome equivalents, it is possible to assemble a small eukaryotic chromosome into 33 contiguous blocks of clones (contigs). With higher clonal densities and more probes, this number can be reduced to less than 5 contigs per chromosome. PMID- 1427047 TI - Deleterious mutations, apparent stabilizing selection and the maintenance of quantitative variation. AB - Apparent stabilizing selection on a quantitative trait that is not causally connected to fitness can result from the pleiotropic effects of unconditionally deleterious mutations, because as N. Barton noted, "...individuals with extreme values of the trait will tend to carry more deleterious alleles...." We use a simple model to investigate the dependence of this apparent selection on the genomic deleterious mutation rate, U; the equilibrium distribution of K, the number of deleterious mutations per genome; and the parameters describing directional selection against deleterious mutations. Unlike previous analyses, we allow for epistatic selection against deleterious alleles. For various selection functions and realistic parameter values, the distribution of K, the distribution of breeding values for a pleiotropically affected trait, and the apparent stabilizing selection function are all nearly Gaussian. The additive genetic variance for the quantitative trait is kQa2, where k is the average number of deleterious mutations per genome, Q is the proportion of deleterious mutations that affect the trait, and a2 is the variance of pleiotropic effects for individual mutations that do affect the trait. In contrast, when the trait is measured in units of its additive standard deviation, the apparent fitness function is essentially independent of Q and a2; and beta, the intensity of selection, measured as the ratio of additive genetic variance to the "variance" of the fitness curve, is very close to s = U/k, the selection coefficient against individual deleterious mutations at equilibrium. Therefore, this model predicts appreciable apparent stabilizing selection if s exceeds about 0.03, which is consistent with various data. However, the model also predicts that beta must equal Vm/VG, the ratio of new additive variance for the trait introduced each generation by mutation to the standing additive variance. Most, although not all, estimates of this ratio imply apparent stabilizing selection weaker than generally observed. A qualitative argument suggests that even when direct selection is responsible for most of the selection observed on a character, it may be essentially irrelevant to the maintenance of variation for the character by mutation-selection balance. Simple experiments can indicate the fraction of observed stabilizing selection attributable to the pleiotropic effects of deleterious mutations. PMID- 1427048 TI - [Genetic analysis of various behavioral and physiologic characteristics in hybrids between hypertensive and normotensive rats. Analysis of reciprocal differences]. AB - As a result of reciprocal crosses between the SHR rats (spontaneously hypertensive strain) and WKY rats (normotensive strain), two types each of the F1 and F2 hybrids and 4 types of backcrosses were obtained. Analysis of reciprocal differences carries out in these generations for a number of behavioral and physiological traits demonstrated linkage of an hereditary factor affecting expression of potassium appetite with the Y-chromosome. The maternal effect contrary to the action of chromosomal hereditary factors was established for locomotor activity in the peripheral zone of open field. This maternal effect was manifested in the F1 and F2 generations, but not in backcrosses. PMID- 1427050 TI - [Chiasma distribution in the lampbrush chromosomes of the chicken Gallus gallus domesticus: hot spots of recombination and their possible role in proper dysjunction of homologous chromosomes at the first meiotic division]. AB - Chiasma distribution in the lambrush chromosomes of the chicken Gallus gallus domesticus was studied. The data of the authors show that the general pattern of chiasmata in the interstitional region of chromosomes corresponds to the Poisson distribution. However, in the telomeric and subtelomeric regions of all chicken macrochromosomes one can see chiasma as a rule. In the half of 140 microchromosomes from 24 different oocytes, there are also the telomeric chiasmata. On the basis of this observation, it may be predicted that there are hot spots of recombination near or into the telomeric GC-rich heterochromatic bands of chicken chromosomes. We suggest that these hot spots of recombination near the telomeres are a necessary facility for not only macrochromosomes but all microchromosomes as well to have at least one chiasma. The constant presence of at least one chiasma in a bivalent in needed for correct disjunction of homologous chromosomes at the first meiotic division. PMID- 1427049 TI - [Genetic analysis of various behavioral and physiologic characteristics in hybrids between hypertensive and normotensive rats. Analysis of correlational connections]. AB - Hereditary links between different behavioral and physiological traits were studied in rat strains SHR, WKY and their hybrids F1 and F2 by analysis of correlations in segregating and nonsegregating gene-rations. Genetic correlation of arterial pressure with body mass, intake of KC1 solution and the ability to avoidance learning (directed positively) and with characteristics of exploratory activity (directed negatively) was shown. These traits seemed to be possible genetic markers of arterial hypertension. Genetical correlates of the ability to elaborate active avoidance conditional reaction (arterial pressure and pain sensitivity) testify to relief of active avoidance learning in animals with inherited active-defensive type of behaviour, manifested by predisposition to pressor reactions and by suppressed emotional reactions to pain stimulation. Frequency in intertrial crossings during avoidance training displays positive correlation with characteristics of exploratory behaviour. Positive correlation between different characteristics of exploratory activity was established both in segregating and nonsegregating generations. PMID- 1427051 TI - [Blood group assignment--a genetic marker of hepatic hemangiomatosis]. AB - There is no single point of view on pathogenesis of hemangiomas. The authors investigated the ABO blood types in 52 patients with hepatic hemangiomas (Group 1) and 1000 control patients (Group 2). The study demonstrated 61.5% of the A blood type among the patients of Group 1. This was significantly higher than in the Group 2 and representative groups from literature (P less than 0.001). Taking into account that the cells of both blood and blood vessels are formed in embryos through the mesenchyma and the heritability of blood group antigens, it is supposed that the results obtained support the genetic determination theory of pathogenesis of hepatic hemangiomas. PMID- 1427052 TI - [Clinical-genealogic analysis of diaphragmatic hernias]. AB - The results of clinical-genetic examination of 174 probands with congenital diaphragmatic hernias and their families are presented. Genetic heterogeneity of diaphragmatic hernias, the spectrum of inherited syndromes obtained in the present study and shown in literature the spectrum and frequency of congenital malformations accompanying diaphragmatic hernias were shown. No increase in the average age of the probands' parents and in the marriage distances changes was observed both for isolated diaphragmatic hernias and those accompanied by other malformations was observed. Because of the high risk of neural tube defects occurrence in the sibs of children with diaphragmatic hernias, the probands' mothers should be recommended to undergo prenatal diagnosis of their further pregnancies for this character. The evidence of multifactorial inheritance for the most of diaphragmatic hernia cases was obtained. Empirical recurrent risk for probands' sibs was 1.54 + 1.5%. PMID- 1427053 TI - [Construction of linear plasmid vectors for cloning in Escherichia coli cells]. AB - Prophage of the temperate coliphage N15 is a linear plasmid with covalently closed ends. The central part of plasmid N15 genome responsible for vegetative phage growth was replaced by DNA fragments containing genes for selective markers which have unique restriction sites. As a result a family of linear plasmid vectors was constructed. Their size is about 20 kb and their capacity is comparable with that of cosmid vectors. PMID- 1427054 TI - [Mechanisms of immunodeficiency in HIV infection and ways of overcoming it]. AB - Though antibodies against HIV-1 appearing in the course of infection are successfully used for the diagnostic purposes, their accumulation on the earlier step leads to: firstly, to the rapid generation of the immunodeficiency by different mechanisms and secondly, to inefficiency of immunotherapy. One of the causes for immunodeficiency seems to be antibodies which are induced in the HIV infected person by the HIV peptides homologous to the MHC class II molecules by their amino acid sequences. 73% of HIV-1 positive sera are shown to react with human B-lymphoma cells expressing surface class II molecule. The binding is caused by the antibodies preventing the murine monoclonal anti-HLA.DR Ab interaction with B-lymphoma. Three amino acid sequences are identified in both alpha- and beta-chain of the HLA.DR antigen, these sequences being homologous to HIV-1 gp120 or gp42 molecules for 50 to 70%. Using synthetic peptides it was shown that HIV-1-infected persons contain antibodies which cross-react to the homologous peptides of the HIV-1 and of the MHC class II. It is supposed that such antibodies shield the class II molecule on the surface of their own antigen presenting cell which may lead to immunodeficiency caused by the anti-HIV-1 antibody. PMID- 1427055 TI - [A system for analysis of yeast mutants deficient in the genetic recombination process]. AB - A system of molecular-genetic methods intended for analysis of yeast Rec-mutants was developed. A number of plasmids containing noncomplementing mutations in the ADE2 gene and different selective markers were constructed. The system was based upon the phenomenon of interplasmid intragenic recombination during transformation and mitotic division. Transformation of yeast cells with the plasmid containing two long right repeats allowed to estimate the efficiency of intraplasmid crossing-over. The system also allows to study plasmid-chromosomal interaction. To check up the system proposed, a well known rad50 and rad52 mutants were used. The rad52-1 mutation was found sharply decreased the levels both intra- and interplasmid recombination events. On the other hand, rad50-1 mutation has not influences or stimulates the processes. Thus, the system proposed efficiently distinguishes the mutants deficient in different stages of recombinational process. PMID- 1427056 TI - [Determination of the minimal length DNA homologous region required for plasmid integration into the Bacillus subtilis chromosome via homologous recombination]. AB - With a view to determine a minimal sequence length of homology necessary for RecE dependent homologous recombination in Bacillus subtilis cells, we developed a system, based on interaction between plasmid replicon and bacterial chromosome. Recombination frequencies were measured between ts plasmid pE194 derivatives carrying chromosomal beta-glucuronidase gene (bglS) fragments of various length, and a bacterial chromosome. The homologous recombination events resulted in bglS gene disruption. Approx. 70 bp of homology were found to be necessary for detectable homologous recombination. Homologous recombination was not detected when homology was equal 25 bp. These data indicate that homology requirement for recombination in B. subtilis differs from that in Escherichia coli. PMID- 1427057 TI - [Mutagenic effect on Escherichia coli bacteria of 8-hydroxy-2'-deoxyguanosine--a DNA base damage product induced by oxygen radicals and ionizing radiation]. AB - The effect of 8-oxo-2'-deoxyguanosine (8-oxo-dG) (8-hydroxydeoxyguanosine)--a DNA base damage product induced by oxygen radicals and irradiation on survival and mutagenesis in Escherichia coli strains C-600 and P-687 was investigated. Survival and mutagenesis curves, in dependence of 8-oxo-dG concentrations in the medium, ranging from 0.2 through 10 mM, were obtained. Bacterial survival at all 8-oxo-dG concentrations tested was shown to be no lesser than in the control. The mutagenic effect of 8-oxo-dG was tested by frequency of reversions in the absence of leucine and threonine. A non-linear dependence of mutagenesis on the concentration was observed. Linear increase in the amount of revertants took place at concentrations of 8-oxo-dG lower than 1 mM, and being kept constant at higher concentrations. Induction of SOS repair under the action of 8-oxo-dG in E. coli PQ37 strain was estimated according to alteration of activity of beta galactosidase in the SOS chromotest. Weak induction of the SOS response was observed within the wide range of 8-oxo-dG concentration values, which points to a lack of genotoxicity and independence of mutagenesis on SOS repair. PMID- 1427058 TI - [Effect of hms mutations increasing spontaneous mutability on induced mutagenesis and mitotic recombination in the yeast Saccharomyces cerevisiae]. AB - The influence of five nonallelic mutations hsm-1-hsm-5 on the frequency of mutations induced by UV-light, 6-hydroxyl-aminopurine (GAP) and nitrosomethylurea (NMM) at the ADE1 and ADE2 loci was studied. All hsm mutants were resistant to the lethal effect of these mutagens. The frequency of mutations induced by UV light was increased in hsm2-1, hsm3-1, hsm5-1 and especially in hsm1-1 mutants, the hsm4-1 mutant not differing from the HSM strain. GAP-induced mutagenesis was elevated in all hsm mutants and, particularly, in hsm3-1. No influence of hsm mutations on the frequency of NMM-induced mutations was observed. The frequency of spontaneous mitotic gene conversion was studied in the diploids heteroallelic for mutations in the gene ADE2 (ade2-58 ade2-i) and homo- and heterozygous for the hsm mutations (HSMHSM and HSMhsm). The mutations hsm2-1, hsm3-1 and especially hsm5-1 strongly increased the conversion frequency for all heteroallelic combinations studied. The mutations hsm1-1, hsm4-1 affected this process weakly. The properties of the hsm mutations under study demonstrated common genetic control of spontaneous and induced mutagenesis and recombination in the yeast. Possible belonging of hsm mutations to the class of mutations destroying the repair pathway for mismatch correction is under discussion. PMID- 1427059 TI - [Homology and evolution of gene orders: combinatorial measure of synteny group similarity and simulation of the evolution process]. AB - Combinatorial measure of synteny group similarity allowing quantitative comparison of evolutional divergence of genomes with the known distribution of homologous genes along the chromosomes is proposed. Computer simulation of chromosome evolution process resulting in gene localization changes was performed. It is sufficient to fix about 50 large rearrangements, like chromosome breakages, fusions and translocations for disappearance of significant similarity between the daughter and parental genomes, in respect of gene distribution in synteny groups. PMID- 1427060 TI - [Inversion polymorphism in the malaria mosquito Anopheles messeae. XI. The group effect of larval infection with Bacillus thuringiensis subsp. israeliensis bacteria]. AB - Genetic consequences of the group and individual infections of Anopheles messeae larvae with bacteria Bacillus thuringiensis subsp. israelensis (Bti) were examined. The group effect of infections was manifested by increase in mortality and the speed-up of selection of chromosomal inversions resistant to Bti. Connection between the group and individual selections during the process of populations' adaptation is under discussion. PMID- 1427061 TI - Cytology of recessive sexual-phase mutants from wild strains of Neurospora crassa. AB - Wild-collected strains of Neurospora crassa harbor recessive mutations that are expressed in the sexual phase when homozygous. Thirty-two representative mutants that produced barren perithecia were examined cytologically. Six of these mutants failed to form asci. Of the remaining 26, chromosome pairing was disturbed in 12 and meiosis was disturbed at pachytene or diplotene in 5. Seven mutants showed normal meiosis I but then diverged from the normal sequence, and two showed perithecial beak abnormalities. In many mutants, ascus development and nuclear divisions continued after the initial defect, albeit abnormally. Nuclear divisions were often delayed, essentially uncoupling them from other ascus events such as the formation of enlarged spindle pole body plaques, ascospore wall membranes, and spore delimitation. All 32 mutants were recessive and none showed obvious morphological abnormalities during vegetative growth. This phenotype contrasts sharply with that of numerous laboratory-induced ascus mutants, which are frequently expressed pleiotropically in the vegetative phase and several are dominant in the sexual phase. PMID- 1427062 TI - Chromosome rearrangement patterns of an SD chromosome (SDKona-2) in Drosophila melanogaster caused by hybrid dysgenesis. AB - The types and frequencies of spontaneous chromosome rearrangements caused by hybrid dysgenesis were studied in a second chromosome autosome of Drosophila melanogaster. This second chromosome, being an SD chromosome, had two important advantages over other autosomes for this study: (i) it had the two inversions characteristic of a standard SD-72 chromosome type, which distinguished it from its homolog in polytene chromosome spreads, and (ii) because of the meiotic drive associated with the segregation distorter system, it was preferentially transmitted to the next generation. The chromosome mutation frequency of this chromosome (given the name SDKona-2) was 8.3 and 11.7% in the F2 and F3 generations, respectively. The types of new chromosome rearrangements observed in the first four generations included paracentric inversions, pericentric inversions, duplications, deletions, reciprocal translocations (involving the third chromosome), and transpositions. Small paracentric inversions were the most common type of new rearrangement. Later, over 35 generations, some of these new rearrangements changed, either by becoming more complex or by being replaced with yet another new chromosome rearrangement. Duplications were unstable and were replaced by paracentric inversions whose breakpoints were on either side of the duplication. Transpositions arose both from a single multibreak event and from a series of two-break events. PMID- 1427063 TI - Genetic analysis of heat shock response in three Drosophila species of the obscura group. AB - Heat shock response was investigated in three species of the obscura group of the Drosophila genus (D. subobscura, D. guanche, and D. madeirensis) by chromosome cytology analysis and [3H]uridine labeling. A set of eight puffs (2C, 15DE, 18C, 27A, 31CD, 85AB, 89A, and 94A) were induced after heat treatments in each of the three species; 18C, 27A, 89A, and 94A were the most heavily labeled in the autoradiograms after the induced conditions. From the in situ results using the major heat shock genes of D. melanogaster as a probe, it was inferred that the 18C, 94A, 89A, and 27A loci of the three obscura group species are homologous to D. melanogaster loci, which contain, HSP82, HSP70, HSP68, and HSPs encoding for the small heat shock proteins, respectively. When this organization was compared with that of D. melanogaster, fewer evolutionary changes, mainly gene duplications, were found to have occurred in the obscura group species than in the D. melanogaster group. In the three species analyzed in this work, as well as in the other Drosophila species studied, the heat shock genes are distributed on D and E Muller's elements, behaving as single copy genes that do not move around the genome. PMID- 1427064 TI - Detection of polymorphic loci in Arachis germplasm using random amplified polymorphic DNAs. AB - The development of easily scoreable genetic markers in Arachis will facilitate the introgression of desirable traits from wild species into adapted germplasm. We have used random amplified polymorphic DNAs (RAPDs) to identify polymorphic molecular markers in a range of wild and cultivated Arachis species. From a total of sixty 10-mer oligonucleotide primers, 49 polymorphic loci were identified between cultivated A. hypogaea type (TMV-2) and a synthetic amphidiploid (B x C)2 created from a A. batizocoi and A. chacoense cross. The inheritance of polymorphic markers, both in the amphidiploid and in the F1 progeny in a TMV-2 x (B x C)2 cross, has also been demonstrated. The potential exploitation of RAPD markers in groundnut improvement programs is discussed. PMID- 1427065 TI - Aspirin-induced asthma: pathogenesis and clinical presentation. AB - In about 10% of adult asthmatics, aspirin precipitates open asthmatic attacks. Pathogenesis, clinical features, and diagnosis of a distinct clinical syndrome known as aspirin-induced asthma are described. The syndrome attracts the attention of scientists and clinicians who are convinced that unraveling its mysteries may give new insights into the pathogenesis of asthma. PMID- 1427066 TI - Management of aspirin-sensitive rhinosinusitis-asthma syndrome: what role for aspirin desensitization? AB - Although aspirin is only one of the triggers of asthma attacks in patients with aspirin-sensitive rhinosinusitis asthma, aspirin sensitivity heralds severe and protracted disease requiring comprehensive management of all components of the syndrome. A review of the literature on the management of patients with aspirin sensitive rhinosinusitis-asthma allows for the establishment of guidelines for conducting aspirin desensitization and evaluating the clinical usefulness of this procedure. PMID- 1427067 TI - Commentary: the American experience with aspirin desensitization for aspirin sensitive rhinosinusitis and asthma. AB - The experience in the United States with aspirin sensitivity associated with rhinosinusitis and asthma is generally in agreement with the European perspective offered by Drs. Szczeklik and Kowalski, though our approach to challenging these patients is slightly different. Most aspirin-sensitive patients no not have a family history of aspirin sensitivity. Aspirin sensitivity is found in one third of patients having nasal polyps, rhinosinusitis, and asthma, the remaining two thirds of these patients having no adverse response to aspirin ingestion. In 85% of asthmatics who give a history of aspirin-induced bronchospasm, oral aspirin challenges are positive. Thus, a small group of patients have inappropriately assigned aspirin-sensitive asthmatic (ASA) as the cause of a prior asthmatic attack that in reality had been induced by an independent provoking factor. PMID- 1427068 TI - A clinical and immunologic study of employees in a facility manufacturing trimellitic anhydride. AB - We conducted a 1-year cross-sectional survey of 474 employees of a large chemical manufacturing complex to relate trimellitic anhydride (TMA) exposure to serologic and clinical outcomes. In 1988-1989, employees were evaluated by history and immunologic assay of total (T) and IgE antibody to trimellityl human serum albumin (TM-HSA). All employees were assigned to a TMA exposure class, from 1 (highest) to 5 (lowest), by an industrial hygienist, independent of the clinical and immunological data. Thirty-two (6.8%) of 474 employees had a TMA immunologic syndrome, 31.6% with an irritant response and 61.6% with no symptoms. Twelve had asthma/rhinitis, 10 had the late respiratory systemic syndrome (LRSS), four had late onset asthma, one had late onset arthralgia, and five had a distant history of LRSS. Included in this survey of the entire work force were 321 new enrollees, who had not joined the previous (1976 to 1988) voluntary surveillance program. Only four (1.3%) of the new enrollee group had a TMA immunologic syndrome. Among new enrollees, there were lower mean total and IgE serum antibody levels in lower exposure classes and a higher percentage with elevated antibody levels in high exposure classes (for T, x2 = 17.5, p = .0016; for IgE, x2 = 76.7, p less than .0001). In the new enrollee population, demographic variables of age, sex, date of hire, and smoking status were examined related to antibody levels. Only current or former smoking was related to elevated total antibody levels. PMID- 1427069 TI - Avicenna on food aversions and dietary prescriptions. PMID- 1427070 TI - Cyclin-B homologs in Saccharomyces cerevisiae function in S phase and in G2. AB - We have cloned four cyclin-B homologs from Saccharomyces cerevisiae, CLB1-CLB4, using the polymerase chain reaction and low stringency hybridization approaches. These genes form two classes based on sequence relatedness: CLB1 and CLB2 show highest homology to the Schizosaccharomyces pombe cyclin-B homolog cdc13 involved in the initiation of mitosis, whereas CLB3 and CLB4 are more highly related to the S. pombe cyclin-B homolog cig1, which appears to play a role in G1 or S phase. CLB1 and CLB2 mRNA levels peak late in the cell cycle, whereas CLB3 and CLB4 are expressed earlier in the cell cycle but peak later than the G1-specific cyclin, CLN1. Analysis of null mutations suggested that the CLB genes exhibit some degree of redundancy, but clb1,2 and clb2,3 cells were inviable. Using clb1,2,3,4 cells rescued by conditional overproduction of CLB1, we showed that the CLB genes perform an essential role at the G2/M-phase transition, and also a role in S phase. CLB genes also appear to share a role in the assembly and maintenance of the mitotic spindle. Taken together, these analyses suggest that CLB1 and CLB2 are crucial for mitotic induction, whereas CLB3 and CLB4 might participate additionally in DNA replication and spindle assembly. PMID- 1427071 TI - Fission yeast genes involved in coupling mitosis to completion of DNA replication. AB - We have isolated fission yeast mutants that enter mitosis when DNA replication is blocked with hydroxyurea. The mutants define eight linkage groups, three of which consist of alleles of the rad1, rad3, and rad17 genes. Recently, these fission yeast genes have been shown to be required for radiation-induced cell cycle arrest, as is the budding yeast RAD9 gene. The other five genes are called hus (hydroxyurea sensitive) 1-5. We propose that these genes participate in an intracellular signal transduction pathway that monitors the completion of DNA replication and transmits information to the mitotic control protein cdc2. Mutations that bypass the requirement for cdc25 (an activator of the mitotic regulator cdc2) also uncouple mitosis from DNA replication. However, mitosis is blocked by inhibitors of DNA replication in strains in which the cdc25 gene has been deleted, indicating that although cdc25 influences the coupling of mitosis to the completion of DNA replication, it is not essential for this control. PMID- 1427072 TI - Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes. AB - Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals. We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2. Using a chimeric protein consisting of the CArG-binding factor p67SRF and the heterologous DNA binding domain of a yeast transcription factor GAL4, we demonstrated that Tax1 activates the transcriptional activity of p67SRF through the GAL4-binding site. The carboxy-terminal half of p67SRF, which lacks domains for DNA-binding, dimerization, and ternary complex formation with p62TCF, was sufficient for the activation by Tax1. Tax1 produced in Escherichia coli bound p67SRF in vitro. The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans. Thus, Tax1 activates CArG-mediated transcription without mitogenic signals through interaction with a CArG-binding factor, p67SRF. This must be one of the primary steps by which Tax1 causes aberration in growth control of the infected cells. PMID- 1427073 TI - The VP16 transcription activation domain is functional when targeted to a promoter-proximal RNA sequence. AB - Among eukaryotic transcription trans-activators, the human immunodeficiency virus type 1 (HIV-1) Tat protein is exceptional in that its target site TAR is an RNA rather than a DNA sequence. Here, we confirm that fusion of Tat to the RNA binding domain of the HIV-1 Rev protein permits the efficient activation of an HIV-1 long terminal repeat (LTR) promoter in which critical TAR sequences have been replaced by RNA sequences derived from the HIV-1 Rev response element (RRE). An RRE target sequence as small as 13 nucleotides is shown to form an effective in vivo target for Rev binding. More important, a fusion protein consisting of Rev attached to the VP16 transcription activation domain was also observed to efficiently activate the HIV-1 LTR from this nascent RNA target. These data demonstrate that trans-activation of transcription by acidic activation domains does not require a stable interaction with the promoter DNA and suggest that VP16, like Tat, can act on steps subsequent to the formation of the HIV-1 LTR preinitiation complex. The finding that the activation domains of VP16 and Tat are functionally interchangeable raises the possibility that these apparently disparate viral trans-activators may nevertheless act via similar mechanisms. PMID- 1427074 TI - Mutations affecting stability and deadenylation of the yeast MFA2 transcript. AB - Decay rates of individual mRNAs in the yeast Saccharomyces cerevisiae can vary by 10- to 20-fold. To determine the basis for the rapid degradation of the mRNA encoded by the yeast MFA2 gene we have used a genetic screen to isolate mutations that increase the stability of this transcript. Analysis of point mutations obtained from this screen, and of additional lesions constructed in vitro, indicated that the MFA2 3'-untranslated region (UTR) contains sequences that specify rapid mRNA decay. Moreover, the lesions that affected mRNA decay rate also affected the process of mRNA deadenylation. Mutations in one region of the 3' UTR both decreased the rate of poly(A) shortening and increased the stability of an intermediate form in the decay pathway with an oligo(A) tail (approximately 10 nucleotides). Mutations in a second region primarily increased the stability of the oligo(A) form. These results suggest that the decay of the MFA2 mRNA initiates with the shortening of the poly(A) tail and there are specific sequences within the 3' UTR that stimulate poly(A) tail shortening as well as subsequent steps in the decay pathway. Given the similarity of this decay pathway to that seen for some mammalian mRNAs, these results suggest that mRNA deadenylation may be a common mechanism of mRNA turnover. PMID- 1427075 TI - An essential splicing factor, SLU7, mediates 3' splice site choice in yeast. AB - Recently, we have reported the identification of several genes that exhibit genetic interactions with the U5 snRNA. Two of these genes, SLU4 and SLU7 (SLU: synergistic lethal with U5 snRNA), encode products required for the second catalytic step of splicing. To analyze the specific roles of SLU4 and SLU7, we have determined how mutants influence the relative usage of competing 3' splice sites. We find that mutations in SLU7 eliminate the normal 20-fold preference for 3' splice sites located > 22 nucleotides downstream of the branchpoint. In contrast, mutations in SLU4 inhibit usage of all 3' splice sites, regardless of their location. This suggests that SLU7 is involved in the process of 3' splice site choice, whereas SLU4 fulfills a generic requirement for the second step. We show that SLU7 is an essential gene that contains a small motif with striking similarity to the cysteine-rich zinc knuckle of retroviral nucleocapsid proteins, which has been implicated in RNA binding. Mutational analysis of SLU7 indicates that this motif influences the efficiency, but not the sequence specificity, of 3' splice site selection. The identification of a component of the constitutive splicing machinery that can promote 3' splice site choice has potentially important implications for alternative splicing. PMID- 1427076 TI - The Drosophila couch potato protein is expressed in nuclei of peripheral neuronal precursors and shows homology to RNA-binding proteins. AB - Through enhancer detection screens we have isolated and cloned an essential gene that is expressed in the neuronal precursors and their daughter cells in the Drosophila embryonic peripheral nervous system (PNS). The gene is named couch potato (cpo), because several partial loss-of-function alleles cause hypoactive behavior in adults. Here, we present evidence that the structure of the cpo locus is unusually complex: It spans > 100 kb, encodes three different messages, is differentially spliced, lacks an AUG initiation codon, and may encode three different proteins. Two putative Cpo proteins contain similar but nonidentical RNA-binding domains that are most homologous to the RNA-binding domains of the Drosophila embryonic lethal abnormal vision (elav) gene and a human brain protein that has been implicated in a paraneoplastic sensory neuropathy. Polyclonal antibodies raised against a fusion protein localize Cpo to the nucleus. Immunocytochemical studies demonstrate that the achaete-scute and daughterless genes are required for proper expression of cpo in the PNS but not in other cells that express cpo. On the basis of our observations, we present a model in which cpo is controlled by genes that determine cells to become PNS cells. Cpo, in turn, may control the processing of RNA molecules required for the proper functioning of the PNS. PMID- 1427077 TI - deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product. AB - Neural precursor cells in Drosophila acquire their identity early during their formation. In an attempt to determine whether all neural precursors share a set of genetic machinery, perhaps to control properties of differentiation common to all neurons, we used the enhancer-trap method to identify several genes (pan neural genes) that are expressed in all neurons and/or their precursors. One of the pan-neural genes is deadpan, which encodes a helix-loop-helix protein closely related to the product of the segmentation gene hairy. The function of deadpan is essential for viability and is likely to be involved in the functional rather than the morphological differentiation of neurons. PMID- 1427078 TI - Allelic diversity of the maize B regulatory gene: different leader and promoter sequences of two B alleles determine distinct tissue specificities of anthocyanin production. AB - The B gene encodes a transcription factor of the basic helix-loop-helix class, which controls the synthesis of the anthocyanin pigments in maize. This gene, as well as the highly homologous R gene family, displays extensive allelic variation in that different alleles cause distinct distributions of anthocyanin pigments in different tissues and at different developmental times. The analysis of the expression of two B alleles, with distinct tissue-specific patterns of anthocyanin synthesis in plant and seed tissues, demonstrates that the amount of B transcripts correlates with the accumulation of anthocyanins in the various tissues. The comparison of the genomic clones for the two alleles reveals high sequence identity in the coding and 3'-flanking regions (98% and approximately 90%, respectively). In contrast, the most 5' region of their mRNAs and the 5' flanking sequences share no significant sequence identity. This result suggests that the alleles diverged from each other by complex genome rearrangements rather than by simple base pair substitutions. We have used the high velocity microprojectile transformation assay to demonstrate that the differential expression of the two alleles in the seed is determined by their 5' variant sequences. Thus, the variation in tissue-specific anthocyanin synthesis in plants with these different B alleles is controlled at the level of B gene expression. PMID- 1427079 TI - Promoter melting and TFIID complexes on Drosophila genes in vivo. AB - In vivo UV cross-linking and nuclear transcriptional run-on experiments have shown that a number of Drosophila genes possess an elongationally paused RNA polymerase on their 5' ends. Here, we examine in vivo promoters that do and do not possess paused polymerases using the single-stranded DNA-probing reagent KMnO4. Melted DNA helices are found associated with the pause site of the uninduced hsp70 and hsp26 heat shock genes and the constitutively expressed beta 1 tubulin gene. The histone H1 and H2B genes, which lack a paused polymerase, have no comparable region of melted DNA. Melting at the pause site persists upon heat shock induction of the hsp70 and hsp26 genes, indicating that pausing continues after gene activation. Interestingly, activation triggers additional melting, both at the start site (in the region where open complexes would be expected to form) and downstream of the uninduced pause site. In the course of our studies, we discovered that some T residues of the TATA box were protected from KMnO4 modification in both induced and uninduced cells. This protection appears to be a consequence of TFIID binding, as a similar protection pattern could be produced in vitro with purified protein. PMID- 1427080 TI - The block to transcriptional elongation within the human c-myc gene is determined in the promoter-proximal region. AB - A conditional block to transcriptional elongation is an important mechanism for regulating c-myc gene expression. This elongation block within the first c-myc exon was defined originally in mammalian cells by nuclear run-on transcription analyses. Subsequent oocyte injection and in vitro transcription analyses suggested that sequences near the end of the first c-myc exon are sites of attenuation and/or premature termination. We report here that the mapping of single stranded DNA in vivo with potassium permanganate (KMnO4) and nuclear run on transcription assays reveal that polymerase is paused near position +30 relative to the major c-myc transcription initiation site. Deletion of 350 bp, including the sites of 3'-end formation and intrinsic termination defined in oocyte injection and in vitro transcription assays does not affect-the pausing of polymerase in the promoter-proximal region. In addition, sequences upstream of +47 are sufficient to confer the promoter-proximal pausing of polymerases and to generate the polarity of transcription farther downstream. Thus, the promoter proximal pausing of RNA polymerase II complexes accounts for the block to elongation within the c-myc gene in mammalian cells. We speculate that modification of polymerase complexes at the promoter-proximal pause site may determine whether polymerases can read through intrinsic sites of termination farther downstream. PMID- 1427081 TI - Escherichia coli RuvA and RuvB proteins specifically interact with Holliday junctions and promote branch migration. AB - The Escherichia coli ruvA and ruvB genes are involved in DNA repair and in the late step of homologous genetic recombination. We have demonstrated previously that the RuvA-RuvB protein complex in the presence of ATP promotes reabsorption of cruciform structures extruded from a supercoiled plasmid with an inverted repeat sequence. Because the cruciform structure is topologically analogous to the Holiday structure, we have proposed that the role of the RuvA and RuvB proteins in recombination is to promote a strand exchange reaction at the Holliday junction. Here, we studied the specific interaction of the RuvA-RuvB complex with the Holliday structure using synthetic analogs prepared by annealing four oligonucleotides. The affinities of the RuvA protein for synthetic Holliday junctions are much higher (> 20-fold) than for duplex DNA, and the affinities of the RuvA protein for the junctions are further enhanced (> 4-fold) by the interaction with the RuvB protein. The RuvA-RuvB protein complex in the presence of ATP promotes dissociation of the synthetic Holliday junction with homology in the central core into two halves by catalyzing branch migration to the DNA ends, but it does not affect the structure of the synthetic Holliday junction without the homology. The separation of the synthetic Holliday junction is a result of the activity of the RuvA-RuvB complex that promotes strand exchange and DNA unwinding. Furthermore, RuvA and RuvB promote the strand exchange reaction at the Holliday junctions made by RecA. These results provide further evidence that the RuvA-RuvB complex recognizes the Holliday junction and promotes branch migration in homologous recombination. PMID- 1427082 TI - Cloning, sequencing, overproduction, and purification of M. CviBI (GANTC) methyltransferase from Chlorella virus NC-1A [corrected]. AB - We have cloned and sequenced the cvibIM gene from Chlorella virus NC-1A by selecting for the modification phenotype. The modification gene was cloned on a 7 kb BamHI fragment inserted into the BamHI site of the pUC13 plasmid. The cvibIM gene was localized at the 3' end of this fragment. Sequencing of this region revealed a large open reading frame that codes for methyltransferase (MTase; symbol M.) (predicting 260 amino acids). M.CviBI (GANTC) aa sequence is homologous to M.Dam(GATC), M.DpnII(GATC), and M.T4 (GATC), and not so to M.HinfI(GANTC), M.HhaII (GANTC), and M.DpnA(GATC). We also describe the use of the polymerase chain reaction technique to alter transcriptional and translational signals surrounding this gene so as to achieve overexpression in Escherichia coli. This construct yields M.CviBI at 2-3% of the total cellular protein. The MTase was purified by phosphocellulose, DEAE, and gel filtration chromatography. Its size by SDS-PAGE is approx. 28 kDa, in good agreement with that predicted from the nucleotide sequence. PMID- 1427083 TI - Protein-coding introns from the 23S rRNA-encoding gene form stable circles in the hyperthermophilic archaeon Pyrobaculum organotrophum. AB - Two archaeal introns have been discovered in the single-copy 23S rRNA-encoding gene of the hyperthermophile, Pyrobaculum organotrophum. After excision from rRNA transcripts, both introns circularize and are stably retained in the cell. Putative proteins encoded by the introns and covering most of the intron sequence share a decapeptide motif with proteins encoded by another archaeal intron and by group I introns. PMID- 1427084 TI - Amino acid substitution in the C-terminal arm domain of HU-2 results in an enhanced affinity for DNA. AB - Three mutants of the Escherichia coli hupA gene, encoding the HU-2 protein, were constructed by synthetic oligodeoxyribonucleotide-directed, site-specific mutagenesis on M13mp18 vectors. The resulting HupAN10, HupAN11 and HupAN12 proteins contained Thr59-->Lys, Gln64-->Lys and Asn53-->Arg substitutions, respectively. These amino acid (aa) changes increased the positive charge of the N-terminal half of the two-strand, antiparallel beta-ribbon of the arm structure, which is believed to be a domain for DNA binding. The three mutant proteins bound to DNA more tightly than wild-type HU-2, and their affinities for DNA increased in the order of HupAN10, HupAN11, HupAN12. The mutant proteins showed a slightly increased HU activity for supporting Mu phage development. A mutant HU-2 protein with increased basicity, but with an altered aa sequence in the arm region due to a frameshift mutation, was also constructed. This mutant protein showed a reduced affinity to DNA and was unable to support Mu growth, suggesting that a unique aa sequence of the arm domain, rather than mere basicity of this domain, is required for efficient binding to DNA. PMID- 1427085 TI - Cloning and characterization of genes involved in the biosynthesis of delta aminolevulinic acid in Escherichia coli. AB - Several mutants of Escherichia coli that had lost their ability to synthesize delta-aminolevulinic acid (ALA) via the C5 pathway were isolated. Their defective loci were classified into two groups, AlaA- and AlaB-. The genes that complemented these mutations were cloned. Nucleotide sequencing indicated that the gene that complemented AlaA- was identical to hemL which is located at 4 min on the E. coli chromosome and encodes glutamate 1-semialdehyde aminotransferase. The gene complementing AlaB- contained an open reading frame (ORF) encoding a polypeptide of 207 amino acids that was found to be a new gene involved in the synthesis of ALA via the C5 pathway. Thus, we designated the gene hemM. The hemM gene was adjacent to hemA that is located at 27 min and previously thought to encode glutamyl-tRNA dehydrogenase. However, we found that hemA complemented both the AlaA- (hemL) and AlaB- (hemM) mutants defective in the C5 pathway although the transformants showed small colonies on the selective medium without ALA. These results suggest that hemA is not involved in the C5 pathway, but controls a second, minor pathway for the synthesis of ALA. PMID- 1427086 TI - Molecular analysis of the recA gene of Agrobacterium tumefaciens C58. AB - The complete nucleotide sequence of the Agrobacterium tumefaciens recA gene was determined. A comparison of the translated open reading frame of the gene with other known recA sequences revealed significant sequence conservation. However, unlike its Escherichia coli equivalent, A. tumefaciens recA lacks the upstream 'SOS box', suggesting a different mechanism of regulation for this gene. PMID- 1427087 TI - A novel Bacillus subtilis expression vector based on bacteriophage phi 105. AB - We have developed a novel expression vector based on the bacteriophage phi 105, and employed it for the production of mutant beta-lactamases in Bacillus subtilis. Expression of the beta-lactamase-encoding gene was low when cloned into the prophage under the control of its own promoter. However, expression was considerably elevated when the gene was inserted into the phage genome in the same orientation as phage transcription. A defective phi 105 vector was constructed with a deletion removing a region needed for cell lysis, and with a mutation in the immunity repressor, rendering it temperature sensitive. Production of beta-lactamase could then be induced by a shift in temperature and without concomitant cell lysis, facilitating purification of the protein from the culture supernatant. This phage has considerable potential for development as a vector for controllable production of heterologous proteins in B. subtilis. PMID- 1427088 TI - Streptomyces lividans glycosylates an exoglucanase (Cex) from Cellulomonas fimi. AB - Exoglucanase Cex from Cellulomonas fimi is a glycoprotein [Langsford et al., J. Gen. Microbiol. 130 (1984) 1367-1376]. Cex produced by Streptomyces lividans from the cloned cex gene is also glycosylated. The extent and nature of glycosylation are similar for Cex from both organisms. The glycosylation affords protection against proteolysis for the enzymes from both organisms when they are bound to cellulose, but not in solution. The ability to glycosylate cloned gene products enhances the utility of Streptomyces as a host for the production of heterologous polypeptides. PMID- 1427089 TI - Isolation and characterization of the gene coding for the major sigma factor of Rickettsia prowazekii DNA-dependent RNA polymerase. AB - The gene coding for the major sigma factor of Rickettsia prowazekii, an obligate intracellular parasitic bacterium, has been isolated utilizing an oligodeoxyribonucleotide as a probe to a conserved region of major sigma factors. Nucleotide sequence analysis revealed an open reading frame of 1905 bp that could encode a protein of 635 amino acids (aa) with a calculated molecular size of 73 kDa (sigma 73). R. prowazekii sigma 73 displayed extensive homology with major sigma factors from a variety of eubacteria. Comparison of the major sigma factors from Escherichia coli and R. prowazekii revealed 44.9% aa identity. R. prowazekii sigma 73 produced in E. coli minicells migrated as a 85-kDa protein when analyzed by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. This anomalous migration is characteristic of eubacterial major sigma factors and agrees with the migration noted for the purified rickettsial sigma protein. Despite a similarity to the E. coli sigma 70 encoded by rpoD, R. prowazekii sigma 73 did not complement E. coli rpoD temperature-sensitive mutants. PMID- 1427090 TI - Automatic elimination of unnecessary bacterial sequences from yeast vectors. AB - Most vectors for Saccharomyces cerevisiae are shuttle vectors which can be both propagated and selected in Escherichia coli. The DNA segments, however, which are required for propagation in E. coli are unnecessary and moreover toxic in S. cerevisiae. To delete these harmful DNA fragments from the vector after it is introduced into S. cerevisiae cells, we propose a specific gene conversion mechanism of a yeast plasmid, pSR1. Plasmid pSR1 has a pair of inverted repeats (IRs) that divides the plasmid molecule into two unique regions. Intramolecular recombination frequently occurs at a pair of specific recombination sites in IRs catalyzed by recombinase R, encoded by a pSR1 plasmid gene. This R-mediated recombination is often accompanied by gene conversion in IRs. Thus, a 2.1-kb pBR322 sequence for the E. coli host ligated into one of the IRs of a composite plasmid was automatically and effectively eliminated when the plasmid was introduced into S. cerevisiae cells. PMID- 1427091 TI - The phenotype of a dihydrofolate reductase mutant of Saccharomyces cerevisiae. AB - We have constructed a dihydrofolate reductase mutant (dfr1) of Saccharomyces cerevisiae. The mutant has auxotrophic growth requirements for the C1 metabolites dTMP, adenine, histidine and methionine, similar to those of wild-type (wt) strains grown in the presence of methotrexate (MTX). However, unlike wt strains treated with MTX, the growth requirements of the dfr1 mutant are not satisfied by exogenous 5-formyltetrahydrofolic acid (FA; folinic acid) in complex (YEPD) medium. This result is surprising, as yeast cells treated with MTX are expected to be phenocopies of dfr1 mutants. The inability of the mutants to metabolize FA suggests that the DFR1 gene product may have a role in folate metabolism in addition to its well-characterized function in the reduction of dihydrofolate. From dfr1 strains, we have isolated secondary mutants whose growth can be supported by FA in YEPD medium. This FA-utilizing phenotype is attributable to recessive mutations which we have designated fou. In addition to their inability to metabolize FA, the dfr1 strains are unable to grow on medium containing the non-fermentable carbon source glycerol, suggesting that the DFR1 gene product is also required for mitochondrial function. In order to overcome this lack of respiratory activity in the dfr1 mutants, we isolated strains containing a dominant mutation, DIR, which allows growth on glycerol in the presence of antifolate drugs. When crossed into dfr1 strains, the DIR mutation conferred respiratory competence. These strains should be useful in a variety of studies on the genetics and biochemistry of folate metabolism in this simple eukaryote. PMID- 1427092 TI - A simple and efficient method for the oligodeoxyribonucleotide-directed mutagenesis of double-stranded plasmid DNA. AB - A method for the oligodeoxyribonucleotide-directed mutagenesis of double-stranded DNA without the necessity for phenotypic selection is described. Plasmids denatured with alkali and purified by adsorption to and elution from nitrocellulose have single-stranded regions where primers can hybridize and serve as templates for a T7 DNA polymerase-catalyzed synthesis of complementary mutant DNA strands. When this procedure was carried out such that the original nonmutant strand contained uracil [method of Kunkel, Proc. Natl. Acad. Sci. USA 82(1985)488 492], mutation frequencies of between 30% and 40% were obtained. The technique has been used to generate mutant genes in plasmids of a wide variety of sizes. The largest plasmid manipulated and successfully mutagenized was 22 kb. The method is rapid and efficient and is not dependent upon either f1 phage vectors or the presence of restriction sites in the vicinity of the sequence targeted for mutation. PMID- 1427093 TI - The carboxypeptidase Y-encoding gene from Candida albicans and its transcription during yeast-to-hyphae conversion. AB - We have cloned and sequenced the gene (CPY1) encoding the carboxypeptidase Y (CPY) of Candida albicans. The gene contains an open reading frame comprising 542 amino acids (aa) with an M(r) of 61,104. The aa sequence shows 74% identity to the mature CPY aa sequence from Saccharomyces cerevisiae. The putative pre (signal) and pro sequences at the N terminus of the C. albicans protein, however, show significant divergence from the corresponding prepro sequence of the S. cerevisiae protein. Southern analysis of C. albicans genomic DNA suggested the presence of only one CPY-encoding gene. Northern analysis during yeast-to-hyphae conversion suggested that the CPY1 gene is transiently down-regulated on a transcriptional level during the early events of this developmental switch. PMID- 1427094 TI - A vector, pSHT, for the expression and secretion of protein domains in mammalian cells. AB - A phagemid (pSHT) containing the pUC and M13 ori sequences was constructed to facilitate the expression of partial cDNAs or of sequences encoding mammalian membrane- and secretory-protein domains. It provides a start codon and signal sequence flanked upstream by the simian virus 40 and bacteriophage T7 promoters and downstream by cloning sites, stop codons in all three frames, splicing and polyadenylation signals. PMID- 1427095 TI - Protein A fusion vectors for use in combination with pEX vectors in the production and affinity purification of specific antibodies. AB - New vectors expressing protein A fusions were constructed, based upon the kanamycin-resistance-encoding plasmid, pK19. They were designed for use in combination with the pEX series of beta-galactosidase protein-fusion vectors in the production and affinity purification of specific antibodies. PMID- 1427096 TI - Characterization of the spontaneous elimination of streptomycin sensitivity (SmS) on high-copy-number plasmids: SmS-enforcement cloning vectors with a synthetic rpsL gene. AB - The strAS or rpsL+ gene, encoding a ribosomal protein, S12, expresses its streptomycin-sensitivity (SmS) phenotype dominantly over strAR or rpsL- gene. Therefore, strAR cells that harbor plasmids with strAS alleles are phenotypically SmS. It was found that the SmS phenotype is unstable, and such cells eventually switch to the Sm-resistance (SmR) phenotype, especially when the strAS gene was cloned on high-copy-number (HCN) plasmids. It seemed that the strA gene cloned on HCN plasmids was toxic to Escherichia coli host cells and, during prolonged cultivation, plasmids with an inactivated strAS gene, mostly carrying insertion sequence elements, such as IS1, IS5 and gamma delta, were selected. The instability of the strA gene was particularly enhanced when the Val51 residue in the middle of S12 protein was replaced by Leu, suggesting enhanced toxicity of the altered S12. Since the strAS gene was stably maintained throughout approx. 100 cell doublings when its expression was abolished, most probably it is the gene product rather than the nucleotide sequence itself that is responsible for the instability of strA gene on HCN plasmids. To improve the stability of the SmS phenotype, the previously reported ampicillin-resistance-conferring and SmS enforcing plasmid vector, pHSG670, was reconstructed. The resulting vector, pHSG683, confers chloramphenicol resistance, enforces SmS on strAR and supE- host bacteria, and has multiple cloning sites within the coding region of synthetic rpsL gene. When pHSG683 DNA was prepared from strAR and sup+ cells grown in tryptophan-rich medium with Cm and Sm, less than 10(-6) plasmids failed to enforce SmS on strAR and supE- cells in tryptophan-less medium with Cm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427097 TI - Synthesis and secretion of an Erwinia chrysanthemi pectate lyase in Saccharomyces cerevisiae regulated by different combinations of bacterial and yeast promoter and signal sequences. AB - Nine different expression-secretion cassettes, comprising novel combinations of yeast and bacterial gene promoters and secretion signal sequences, were constructed and evaluated. A pectate lyase-encoding gene (pelE) from Erwinia chrysanthemi was inserted between each one of these expression-secretion cassettes and a yeast gene terminator, generating recombinant yeast-integrating shuttle plasmids pAMS1 through pAMS9. These YIp5-derived plasmids were transformed and stably integrated into the genome of a laboratory strain of Saccharomyces cerevisiae, and the pectate lyase production was monitored. Transcription initiation signals for pelE expression were derived from the yeast alcohol dehydrogenase (ADC1P), the yeast mating pheromone alpha-factor (MF alpha 1P) and the Bacillus amyloliquefaciens alpha-amylase (AMYP) gene promoters. The transcription termination signals were derived from the yeast tryptophan synthase gene terminator (TRP5T). Secretion of pectate lyase (PLe) was directed by the signal sequences of the yeast mating pheromone alpha-factor (MF alpha 1S), B. amyloliquefaciens alpha-amylase (AMYS) and Er. chrysanthemi pectate lyase (pelES). The ADC1P-MF alpha 1S expression-secretion system proved to be the most efficient control cassette for the expression of pelE and the secretion of PLe in S. cerevisiae. PMID- 1427098 TI - Sequence of a cluster of genes controlling synthesis and secretion of alkaline protease in Pseudomonas aeruginosa: relationships to other secretory pathways. AB - A genetic locus implicated in the synthesis and secretion of alkaline protease (APR) in Pseudomonas aeruginosa has been previously described [Guzzo et al., J. Bacteriol. 172 (1990) 942-948]. The nucleotide sequence of the DNA fragment encoding these functions was determined and revealed the existence of five open reading frames: aprA, the structural gene encoding APR; aprI, which encodes a protease inhibitor; and aprD, aprE, aprF whose products are involved in protease secretion. The AprD, AprE and AprF proteins share significant homology with proteins implicated in secretion of Erwinia chrysanthemi proteases and Escherichia coli alpha-haemolysin. These results provide further evidence for the existence of a specialized secretory system widespread among Gram- bacteria. PMID- 1427099 TI - Genetic suppression analysis of sigma E interaction with three promoters in sporulating Bacillus subtilis. AB - Genetic evidence suggests that the sigma (sigma) subunit of RNA polymerase determines the specificity of promoter utilization, by making sequence-specific contacts with DNA. We examined the effects of two single amino acid(aa) substitutions in sigma E on the utilization of mutated derivatives of three different promoters in sporulating Bacillus subtilis. We found allele-specific suppression of mutations in all three promoters by each aa substitution in sigma E. These results provide strong evidence that sigma E interacts with each of these promoters in vivo. Moreover, the specificity of suppression of the mutations by the aa substitutions in sigma E lead us to speculate that the Met124 of sigma E closely contacts two adjacent bp in the -10 region of the promoters. PMID- 1427100 TI - Cloning, sequencing and expression in Escherichia coli of the ptsI gene encoding enzyme I of the phosphoenolpyruvate:sugar phosphotransferase transport system from Streptococcus salivarius. AB - We present the cloning and sequencing of the ptsI gene, encoding enzyme I (EI) of the phosphoenolpyruvate (PEP): sugar phosphotransferase (PTS) transport system from Streptococcus salivarius. The ptsI gene corresponds to an open reading frame of 1731 nucleotides, which translates into a putative 577-amino acid (aa) protein with a M(r) of 62,948 and a pI of 4.49. The EI was produced in Escherichia coli under the control of its own promoter located immediately upstream of ptsI, a situation never previously reported for any other gene coding for an EI. The deduced aa sequence of the S. salivarius EI shows a high degree of similarity with the E. coli EI and the EI moiety of the multiphosphoryl transfer protein from Rhodobacter capsulatus. The S. salivarius EI also shares a highly conserved aa cluster with a non-PTS protein, the maize pyruvate:orthophosphate dikinase. The conserved cluster is located in a domain which is hypothesized to be the PEP binding site. PMID- 1427102 TI - The rate of decay of Rhodobacter capsulatus-specific puf mRNA segments is differentially affected by RNase E activity in Escherichia coli. AB - In Rhodobacter capsulatus the puf operon encodes proteins of the photosynthetic apparatus. The polycistronic puf mRNA is comprised of segments that show differential stability. Here, we show that the rate of decay of the 2.7-kb pufBALMX mRNA species in Escherichia coli depends on the activity of ribonuclease E (RNase E), whereas the degradation of the 0.5-kb pufBA mRNA segment is not affected by a mutation in the rne gene. The RNase E-promoted decay of the pufLMX mRNA depends on the presence of a 1.4-kb pufLM mRNA segment, in which rate limiting endonucleolytic cleavage was postulated to occur in R. capsulatus. The insertion of 185 bp of this 1.4-kb segment into pufB results in an RNase E dependent decay of the modified pufBA mRNA segment in E. coli. Our findings suggest that in R. capsulatus an RNase E-like activity is responsible for the rate-limiting endonucleolytic cleavage occurring within the pufLM mRNA segment, whereas the 0.5-kb pufBA mRNA segment is degraded by a different RNase E independent decay mechanism. PMID- 1427103 TI - HIV virus: older adults may not fall into known risk groups. PMID- 1427101 TI - Cloning and sequence analysis of the gene encoding an NADP-dependent alcohol dehydrogenase in Mycobacterium bovis BCG. AB - The nucleotide sequence of a 1619-bp fragment of Mycobacterium bovis BCG containing the gene that encodes an alcohol dehydrogenase (ADH) has been determined. The M(r) calculated from the deduced amino acid (aa) sequence, as well as the N terminus, are in good accordance with those determined for the ADH purified from M. bovis BCG extracts. The M. bovis BCG cloned adh gene was expressed in Escherichia coli by its own promoter and the synthesized product shows ADH activity in the butane-1-ol-NADP system. Based on comparison of the aa sequence, this enzyme belongs to the zinc-containing, long-chain alcohol/polyol dehydrogenase family, which has been primarily described in eukaryotes. Of the 22 strictly conserved residues in this group, 19 are also conserved in M. bovis BCG ADH (BCGADH). PMID- 1427104 TI - Colonic and anorectal disorders: diagnosis and treatment. AB - Older patients are at increased risk of colonic and anorectal disorders, some of which occur commonly in patients of all ages. A careful medical history and physical examination, knowledge of the past medical history, and assessment of the circumstances in which symptoms of intestinal disease develop allows intelligent direction of the medical evaluation. Direct visualization of the colorectal mucosa using flexible fiberoptic or videoendoscopes often provides prompt and accurate diagnosis and facilitates therapeutic intervention. Other disorders require radiologic diagnosis and treatment or surgical intervention. PMID- 1427105 TI - Health care for all: comparing proposals for reform. A roundtable discussion: Part 2. AB - Part 1 of this roundtable discussion [Geriatrics 1992; 47(Sept):34-48] examined the flaws in our current healthcare system and factors that are interfering with our nation's ability to achieve reforms. This month, the panelists discuss the benefits and drawbacks of the major healthcare reform proposals, including managed care, single-payer systems, and so-called "play or pay." The practical aspects of any redistribution of healthcare resources are considered as each panelist outlines a favored approach. The influence of special interests, such as the insurance industry, is also discussed. PMID- 1427106 TI - A rational approach to urinary tract infections in older patients. AB - Urinary tract infections (UTIs) occur more commonly in the elderly than in younger adults. The frequency of concomitant chronic illness and decreased resistance in this age group confers increased rates of morbidity and mortality, and manifestations are often atypical. Diagnosis requires careful interpretation of urine culture results and a determination of the infection as asymptomatic bacteriuria, uncomplicated UTI, or complicated UTI. This, in turn, guides therapeutic measures, including the use of oral antibiotics. PMID- 1427107 TI - Preventive nutrition: an 'optimal' diet for older adults. AB - Nutritional screening, an important aspect of prevention, includes measurement of height and weight, laboratory values as indicated, and a dietary assessment. For primary prevention, nutrition information should be broad enough to maintain health and prevent disease in healthy persons. Recommendations need to address problems of dietary excess as well as the possibility of nutrient inadequacy. Although controversial, the routine recommendation of a basic multivitamin and mineral supplement for healthy older adults is favored by these authors. PMID- 1427108 TI - Night people: avoiding the quick fix for insomnia. PMID- 1427109 TI - Age-based rationing of health care: the only system that makes sense? PMID- 1427110 TI - Family service centers. PMID- 1427111 TI - Education and research: key components of healthcare reform. PMID- 1427112 TI - Preventive nutrition: disease-specific dietary interventions for older adults. AB - Disease prevention through dietary management is a cost-effective approach to promoting healthy aging. Fats, cholesterol, soluble fiber, and the trace elements copper and chromium affect the morbidity and mortality of CHD. Decreasing sodium and increasing potassium intake improves control of hypertension. Calcium and magnesium may also have a role in controlling hypertension. The antioxidant vitamins A and beta-carotene, vitamin C, vitamin E, and the trace mineral selenium may protect against types of cancer. A decrease in simple carbohydrates and an increase in soluble dietary fiber may normalize moderately elevated blood glucose levels. Deficiencies of zinc or iron diminish immune function. Adequate levels of calcium and vitamin D can help prevent senile osteoporosis in both older men and women. PMID- 1427113 TI - Health care for all: long-term care, the missing piece. A roundtable discussion: Part 3. AB - Long-term care has been described as the "missing piece" in many healthcare reform proposals. Yet the cost of nursing home care often exceeds that of acute care, especially for the elderly with Alzheimer's disease. In this final installment of a three-part roundtable discussion, panelists discuss the options for providing long-term care, such as social insurance, a single-payer system, play or pay, or private insurance models. Alternatives to nursing home care, such as community service centers and home care, are discussed. The panelists conclude with an examination of how these proposed reforms might affect the practices of physicians and the U.S. economy. PMID- 1427115 TI - Physicians' groups endorse national healthcare budget, negotiated fee limits. PMID- 1427114 TI - Clinical evaluation of the patient with ventricular arrhythmia. AB - Evaluation of patients with ventricular arrhythmia (VA) is a frequently encountered problem in clinical practice. Determining which patients require treatment and which are at risk for sudden cardiac death remains challenging, however. Classification of VAs as significant, prognostically important, having unknown importance, or insignificant will help determine whether treatment is warranted and beneficial. Tests for evaluating suspected VA, including ambulatory electrocardiographic monitoring, exercise testing, and electrophysiologic studies, are used to determine the presence or frequency of an arrhythmia, correlate the arrhythmia with symptoms, determine a prognosis, or evaluate the efficacy of drug therapy. PMID- 1427116 TI - Norepinephrine content in cardiovascular tissues from the aged Fischer 344 rat. AB - The major aim of the present study was to examine cardiovascular tissues and to determine if norepinephrine (NE) stores declined in aged (22-30 months old) male Fischer 344 (F344) rats. NE content was measured by HPLC in the whole heart, ventricle, atria, caudal artery, renal arteries, portal vein and kidney. The release of [3H]NE from the caudal artery of adult and aged rats was assessed as a functional index of sympathetic innervation. Renal alpha 2-adrenergic binding sites were also determined using 2.0 nM [3H]rauwolscine. In general, total NE content per organ was not altered in aged rats. The exception was the ventricle of aged rats which exhibited a 25% decrease in NE content. In contrast, NE content per gram of tissue weight was significantly decreased in the whole heart, atria, ventricle, kidney and caudal artery of aged rats when compared to that of adults (6-8 months old). Neither basal nor potassium-stimulated NE release was altered in the caudal artery of aged rats. Presynaptic regulation of NE release by taurine and alpha 2-adrenoceptors was also not affected by age. Renal alpha 2 adrenergic binding sites were decreased 23% in aged rats. Tissue growth that occurs as a function of aging does not appear to receive a concomitant increase in sympathetic growth as indexed by NE content. The findings of the present study would lead to the conclusion that with the exception of the ventricle, sympathetic nerve terminals of the aged male F344 rat are relatively intact. PMID- 1427118 TI - Age-related changes in collagen of human intervertebral disks. AB - Age-related changes of human intervertebral disk collagen have been investigated. A progressive, age-related accumulation of collagen, both in annulus fibrosus and in nucleus pulposus was found. A decrease in collagen solubility was observed during physiological aging. Up to the 3rd-4th decades of life, a significant increase in the aldehyde content in disk collagen has been observed. Nuclei pulposi of the prolapsed disk contain more collagen, and its solubility was higher in comparison to corresponding necropsy material. Some alterations in the collagen of prolapsed disks may be considered as symptomatic of accelerated aging. PMID- 1427117 TI - Effect of propyl gallate feeding on glutathione content in ageing Zaprionus paravittiger (Diptera). AB - Glutathione content increased during the reproductive period and decreased thereafter up to the 43rd day of age in whole body as well as mitochondrial homogenates of ageing Zaprionus paravittiger. However, females exhibited higher levels of glutathione as compared to males. In whole body homogenates, propyl gallate (PG; 25 micrograms/ml) increased the glutathione content significantly up to the 22nd day of life whereas in mitochondria it increased during all age intervals in the two sexes with the exception of the 36th and 43rd day of survival in males. In conclusion, the higher level of glutathione on PG feeding might be one of the factors leading to the prolonged life span of flies. PMID- 1427119 TI - Hematocrit and cardiovascular risk factors among elderly men and women (Dutch Nutrition Surveillance System). AB - Changes in whole blood viscosity associated with hematocrit could be one of the pathways along which the cardiovascular disease (CVD) risk factors affect these diseases. Therefore, we studied in a nationwide survey comprising 514 apparently healthy Dutch elderly men and women aged 65-79 the possibility of any association between hematocrit and CVD risk factors (tobacco smoking, serum cholesterol, body mass index and blood pressure). Among men, diastolic blood pressure and total serum cholesterol were positively associated with hematocrit in both bivariate and multivariate regression analysis, whereas positive associations of hematocrit with body mass index and smoking were only significant (p < 0.05) in bivariate analysis. Among women, hematocrit was positively associated with body mass index and smoking. Except for smoking, which was associated with the mean corpuscular volume of the erythrocytes, hematocrit was positively correlated with hemoglobin and the number of erythrocytes. It is concluded that hemorrheological aspects should be considered when studying CVD among elderly people. PMID- 1427120 TI - Nosocomial infection and antibiotic utilization in geriatric patients: a pilot prospective surveillance program in skilled nursing facilities. AB - Prospective surveillance of nosocomial infection was conducted at seven skilled proprietary nursing facilities in Orange County, Calif., USA. The average incidence of facility-acquired infection was 5.2 infections/1,000 patient days. The most common source of infection was urinary tract (47%), followed by respiratory tract (26%) and skin (14%). The four most common pathogens isolated were Proteus spp. (20%), Escherichia coli (17%), Staphylococcus aureus (13%) and Pseudomonas spp. (11%). Trimethoprim-sulfamethoxazole (20%) was the most frequently used antibiotic among all prescriptions, followed by ampicillin (16%) and ciprofloxacin (14%). Among all residents surveyed, 33% received at least one course of antibiotics during the study. Of special significance was the fact that 4 (22%) of the 18 strains of Pseudomonas were gentamicin resistant as were 12 of 80 (15%) of the strains of Enterobacteriaceae. Furthermore, 9 of 29 (31%) strains of Pseudomonas tested were found resistant to norfloxacin as were 15 of 129 (12%) strains of enterobacteriaceae. Susceptibility patterns of the isolated pathogens were similar to those of the acute care hospital. This study indicates that infection continues to be a major problem in the skilled nursing facility and that antibiotic-resistant pathogens will be a challenge for the future. PMID- 1427121 TI - Leuko-araiosis and event-related potentials (P300) in normal aged subjects. AB - To investigate the relationship between cerebral leuko-araiosis and cognitive function in normal aged subjects, 48 neurologically normal aged volunteers (24 males, 24 females, 64-85 years old, mean age 75.2 years) with no silent lacunar lesions on their MRI images were examined. The severity of periventricular hyperintensity was estimated quantitatively based on the T1 values on MRI. Cognitive function was evaluated on the basis of P300 event-related potentials employing an auditory oddball paradigm. The severity of frontal lobe leuko araiosis significantly increased with advancing age (p < 0.05), however, P300 latency was not correlated with age. There was no significant correlation between the severity of leuko-araiosis and P300 latency. The severity of leuko-araiosis was correlated with mean arterial blood pressure (p < 0.05). These results suggest that the severity of leuko-araiosis may be unrelated to cognitive function in normal aged subjects and that arterial blood pressure may contribute to the progression of leuko-araiosis. PMID- 1427122 TI - Increased mechanical strength of left colon in old rats treated with growth hormone. AB - The effects of treatment with 2.7 mg biosynthetic human growth hormone (b-hGH; 2.7 mg/kg b.w./day) for 80 days on the biomechanical properties and collagen deposition of the left colon were studied in 27-month-old male rats. The b-hGH treated rats increased in body weight by 17%, and the wet weight of colon by 31%. The defatted dry weight and the hydroxyproline content of the left colon were increased by 41 and 29%, respectively, compared with controls. The biomechanical analysis showed that the maximum load and stiffness of the left colonic specimens in the b-hGH-treated group were enhanced by 27 and 60%, respectively, and the strain at maximum load was 24% less than in the control group. The maximum 'stress' and stiffness were 40 and 73% higher, respectively, than in the controls. Histological examination demonstrated that the mean crypt heights was 9% higher in the b-hGH-treated rats than in the controls. Consequently, treatment of old rats with b-hGH may increase the strength, collagen deposition and mucosal crypt height of the left colon. PMID- 1427123 TI - Changes in catalase activity and its thermolability in liver and kidneys of ageing male garden lizard. AB - Catalase activity in liver and kidneys of male garden lizards remained unchanged during maturation, but showed an increase during ageing. Instead of inactivating catalase, thermal treatment at 60 +/- 1 degree C caused a marginal increase in enzyme activity in the liver of middle-aged and kidneys of young lizards with no significant effect in old counterparts. Increase in basal enzyme activity during ageing and the maintenance of resistance against thermal inactivation of the enzyme throughout the life-span support the contention that catalase molecules in lizard tissues are not altered as a function of age, a deviation from the predictions of Orgel's error catastrophe hypothesis. PMID- 1427125 TI - An investigation of the relationship between free radical activity and vitamin C metabolism in elderly diabetic subjects with retinopathy. AB - Abnormalities of both free radical activity and ascorbic acid metabolism have been documented in diabetes, but their biological basis is unclear and their relationship unstudied in any detail. This study was designed to compare changes in antioxidant status and free radical reactions in a group of elderly diabetic patients (with and without retinopathy) with those in a group of age-matched control subjects. No significant differences in thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations or diene conjugates (DC) between patients and controls were seen despite significant depletion of ascorbic acid in patients with diabetes, especially in those with retinopathy. The results emphasise the present-day difficulties of measuring free radical activity and demonstrate a marked abnormality in ascorbic acid metabolism in diabetes. PMID- 1427124 TI - Participation of decreased serum cholesteryl ester transfer activity, independent of increased serum lipoprotein(a), in angina pectoris in normolipemic elderly subjects. AB - The cholesteryl ester transfer activity (CETA) is a measurement of the transfer of cholesteryl ester from HDL to VLDL, LDL or peripheral cells. Its role in the development of early coronary heart disease is not clear. In the present study, serum levels of CETA, lipoprotein(a) [Lp(a)] and other lipid-related factors were compared in 10 normal young subjects, 28 healthy elderly subjects and 14 normolipemic elderly patients with angina pectoris. Compared to the young normals and healthy elderly subjects, the elderly patients with angina pectoris showed significantly decreased mean serum CETA levels, and significantly increased mean serum levels of Lp(a) and apoprotein B. These results may indicate that decreased serum values of CETA participate in the development of angina pectoris in normolipemic elderly patients. PMID- 1427126 TI - Lack of association of nonsteroidal anti-inflammatory drug use and cognitive decline in the elderly. AB - Folstein Mini-Mental State Examination (MMSE) scores obtained in an ambulatory elderly population were used to examine the effect of nonsteroidal anti inflammatory drug (NSAID) use on cognitive performance. There were 1,310 participants who met the inclusion criteria for the study, of whom 873 (66.6%) were women and 437 (33.3%) were men. There were no differences in mean MMSE scores or in the five dimensions of cognitive function measured by the MMSE for subjects reporting NSAIDs or aspirin use. PMID- 1427127 TI - Vitamin-D-fortified liquid milk--a highly effective method of vitamin D administration for house-bound and institutionalised elderly. AB - The aim of the study was to assess the efficacy and acceptability of vitamin-D fortified liquid milk in the management of hypovitaminosis D in an elderly institutionalised population. The design was a single-blind randomised controlled study. In phase I, patients were encouraged to drink an increased quantity of either fortified or unsupplemented milk for 3 months. In phase II, patients were continued on either fortified or on unsupplemented milk which was given as part of the everyday diet for a further 6 months with no extra encouragement of any patient to take additional amounts. Ninety-eight patients (mean age 84 years) from extended care wards at the Department of Medicine for the Elderly, St. James's Hospital, Dublin, Ireland, participated in the study. Seventy-eight patients completed phase I, and 62 completed phase II. A general biochemical screen and 25-hydroxy vitamin D measurements were performed at entry and repeated 3 and 9 months later. The average milk intake per patient in phase I was 454 ml/day in the unsupplemented group and 359 ml/day in the fortified milk group. In phase II, the average daily milk intake per patient was 235 ml in the unsupplemented milk group and 140 ml in the fortified milk group. Seventy-four patients (94%) of the total who completed phase I had serum vitamin D baseline levels below the normal range. In the fortified milk group, mean vitamin D levels rose from 2.4 to 14.80 ng/ml (p < 0.001) at the end of phase I and remained significantly elevated at 10.2 ng/ml (p < 0.001) at the end of phase II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427128 TI - Brain atrophy on computerized axial tomography scans: interaction of age, diabetes and general morbidity. AB - We evaluated, retrospectively, the occurrence of brain atrophy in all patients (n = 416) with a brain CT scan performed during a 3-month period in 1989 at the Tampere University Central Hospital. Age, diabetes, hypertension, chronic cerebrovascular disorders and an increasing number of medications were associated with brain atrophy in the log-linear models. We suggest that the effect of various systemic medical disorders on the brain requires consideration when evaluating and assessing physiological ageing of the brain. PMID- 1427129 TI - Randomised controlled trial of exercise in the elderly. AB - Eighty-seven healthy volunteers aged 60-81 years were randomly allocated to either an aerobic exercise class or a health education group. Only 6 subjects dropped out during the 32-week study, and the average compliance with the interventions was 83% for exercise (on average 83/100 individual exercise sessions were attended) and 71% for health education. The health education group showed improvements from the baseline in physical activity levels, pulse rate, blood pressure and self-rating of mood. The exercise group improved from baseline in knee and spine flexibility, leg and back strength, pulse rate, blood pressure, maximum physical exertion levels, self-rating of mood and perceived health status. Between group comparison at the end of the study showed the exercise group significantly better than the health education group in terms of spine flexion (p < 0.0001), perceived health status (p < 0.05), life satisfaction (p = 0.05) and maximal physical exertion (p = 0.01). This study has demonstrated the acceptability and effectiveness of an aerobic exercise class for the elderly, and the effectiveness of health education for this age group. PMID- 1427130 TI - Exfoliation syndrome as a risk factor for optic disc changes in nonglaucomatous eyes. AB - Exfoliation syndrome as a possible risk factor for morphologic changes of the optic nerve was examined in 66 patients with unilateral exfoliation and no glaucoma. K-readings (7.74 +/- 0.3 mm and 7.75 +/- 0.3 mm), axial lengths (23.1 +/- 1.1 mm and 23.1 +/- 1.1 mm), and refraction (+ 0.9 +/- 2.3 mm and + 1.1 +/- 2.3 mm) did not differ in exfoliative and contralateral nonexfoliative eyes. The mean intraocular pressure (IOP) difference, 17.2 +/- 3.3 mmHg and 15.6 +/- 3.2 mmHg, respectively, was statistically highly significant (P < 0.001). The mean visual acuity difference, 0.8 +/- 0.3 and 0.9 +/- 0.2, respectively, was significant (P < 0.05). The difference in visual acuity between the pairs of eyes was explained by the more frequent subcapsular cataract in exfoliative eyes. Lens opacity values (opacity lens meter), 27.9 +/- 8.3 and 28.0 +/- 8.4 opacity units, respectively, were similar. Disc area, neuroretinal rim area, rim/disc ratio, cup area, and cup volume values analyzed with the Imagenet (Topcon) nerve head analyzer did not differ significantly between the eyes. It was concluded that exfoliation as such does not induce optic nerve head changes but indicates a risk factor for elevated IOP and lens opacification. PMID- 1427131 TI - Count and density of human retinal photoreceptors. AB - This investigation was directed at determining the count and regional distribution of photoreceptors in the eyes of 21 human cornea donors aged between 2 and 90 years. Mean count of rods was 60,123,000 +/- 12,907,000, and mean cone count was 3,173,000 +/- 555,000. Determined 40 microns away from the foveola, cone density measured 125,500 cones/mm2. Extrapolating the distribution curve, cone concentration in the foveal center can be assumed to be about 150,000 cells/mm2 to 180,000 cones/mm2. Towards the retinal periphery, cone density decreased from 6000 cones/mm2 at a distance of 1.5 mm from the fovea to 2500 cells/mm2 close to the ora serrata. Comparing different fundus regions, cone concentration was significantly highest in the nasal region. Cone diameter increased from the center towards the periphery. At a distance of 40 microns away from the foveola, it measured about 3.3 microns, and in the outer retinal regions about 10 microns. Rod density was highest in a ring-like area at a distance of about 3-5 mm from the foveola with a mean of 72,246 +/- 17,295 cells/mm2. Rod density peaked at 150,000 rods/mm2. It decreased towards the retinal periphery to 30,000-40,000 rods/mm2. Rod diameter increased from 3 microns at the area with the highest rod density to 5.5 microns in the periphery. The hexagonal rod and cone inner segments were regularly arranged in a honey-comb fashion. PMID- 1427132 TI - Parameters associated with papillomacular bundle defects in glaucoma. AB - To evaluate the relationship between the papillomacular bundle defect and glaucoma types, abnormalities of the optic disc, distance between the disc and foveola, and axial length, we examined one eye of 82 patients with normal tension glaucoma, 117 patients with chronic high tension glaucoma, and 102 controls. Two types (diffuse and focal types) were found in the papillomacular bundle defect, and the former predominated. Eyes with a long axial length (P < 0.01), a diagnosis of normal tension glaucoma (P < 0.05), or a large optic disc (P < 0.05) tended to have diffuse-type papillomacular bundle defects, while eyes with a short axial length, a diagnosis of high tension glaucoma, or a large ovalness index are less likely to have it. Thus, a long axial length, a large optic disc, and normal tension glaucoma are risk factors for the diffuse-type papillomacular bundle defect. PMID- 1427133 TI - Acetazolamide but not timolol lowers aqueous humor flow in sleeping humans. AB - The effect of timolol, acetazolamide, and the combination of the two drugs on the rate of aqueous formation in 18 healthy human subjects was measured during the day and at night in a placebo-controlled, double-masked, randomized study. In the absence of any drugs, aqueous flow during the day was 2.61 +/- 0.82 (mean +/- SD) microliters/min and at night, 1.08 +/- 0.59, a 59% lower flow rate when compared with the daytime value (P < 0.0001). When compared with these aforementioned control values, timolol alone reduced the rate of aqueous flow by 39% (P < 0.0001) in awake subjects but had no statistically significant effect on the flow rate in sleeping subjects (P = 0.33). Acetazolamide alone reduced aqueous flow during the day by 21% compared with the control flow rate (P = 0.02) and at night by 24% below the nocturnal flow rate in the sleeping eye (P = 0.04). The combination of the two drugs reduced flow during the day by an additional 13% (P = 0.024) compared with the flow rate achieved by timolol alone, and by an additional 32% (P < 0.0001) compared with the flow rate reduction attained by acetazolamide alone. There was no statistically significant difference in the nocturnal flow rates achieved by acetazolamide alone or in combination with timolol (P = 0.37). These data confirm previous studies demonstrating the effect of timolol, acetazolamide, and sleep on the rate of aqueous humor formation. Unlike a previous study, it was found that acetazolamide lowers the aqueous flow below the already low nocturnal flow rate that occurs spontaneously in the sleeping eye.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427134 TI - The relationship between intraocular pressure and visual field progression in glaucoma. AB - The purpose of this study was to determine the intraocular pressure characteristics in glaucoma suspects and patients whose visual fields were classified as stable or progressing over a long-term follow-up. We present data from 64 patients who received either medical or laser treatment and who were followed up for a median of 7.4 years. The visual fields of 27 patients were classified as stable and 37 as progressing using predetermined criteria on either the Tubinger or Goldmann perimeter. Patients with initially normal and initially abnormal fields were analysed separately to avoid bias. There were no significant group differences in the mean, highest or interquartile range of intraocular pressure in the follow-up. The largely overlapping distributions over a wide spectrum of the pressure variables in patients with stable and progressing fields show that intraocular pressure alone cannot separate these two groups of patients. Our study does not suggest that pressure reduction in glaucoma has no beneficial effect, but that there may be other factors which determine the fate of the visual field in glaucoma. PMID- 1427136 TI - The pathology of abortive neovascular outgrowths from the retina. AB - Seven abortive neovascular outgrowths (ANVOs) from diabetic retinas were obtained for examination either by biopsy during pars plana vitrectomy (2) or after discovery within enucleated globes (5). Scanning and electron microscopical, histochemical, immunohistochemical and retinal digest techniques were used. The ANVOs consisted of nodules of vessels without an extravascular fibrous component. Two of them contained aneurysm-like dilatations of constituent vessels, and all the specimens showed gross hyaline thickening of the vessel walls. The vascular sclerosis was probably due to accumulation of plasma proteins in the walls of the damaged vessels, which contributes to their involution seen clinically after retinal photocoagulation. PMID- 1427135 TI - Metastatic tumors to the orbit--management and prognosis. AB - In a retrospective study the records of 34 consecutive cases with tumors metastatic to the orbit were reviewed with special attention to the management and prognosis of these patients. The primary tumor site was the breast in 20 patients, prostate in 5, kidney in 2 and skin in 2. The remaining 5 patients had other primary tumour sites. The symptoms of orbital metastasis preceded the detection of the primary tumor in 8 cases (24%). Twenty patients died after a mean interval of 25 months following the diagnosis of the orbital metastasis. This study gives a summary of the clinical features of these patients. With improved methods of treatment it was possible to obtain a relief of orbital symptoms in 24 patients (71%). Although the life expectancy of these patients remains poor, treatment can result in symptomatic relief and in an improvement in the quality of life, which is the main goal in the management of these patients. PMID- 1427137 TI - Use of the argon laser to close filtering bleb leaks. AB - We attempted to seal 15 consecutive filtering bleb leaks in 11 patients using argon laser energy. Eight leaks were at the conjunctival-corneal interface associated with a fornix-based flap, 4 leaks resulted from suture scissoring of the conjunctiva, and 3 leaks were button-holes in the conjunctiva. Thirteen leaks occurred within 2 weeks after filtering surgery, while 2 were of late onset. Argon laser parameters used were a 500-microns spot size, 0.1-s time interval, and between 500 and 1800 mW of power. Thirteen leaks were sealed after one or two laser sessions, while 2 leaks required other treatment modalities. Complications included conjunctival fenestration and transient corneal stromal opacities. This study suggests that the argon laser can be used to seal filtering bleb leaks in many patients following filtering surgery. PMID- 1427138 TI - Intraocular pressure-related pattern of optic disc cupping in adult glaucoma patients. AB - The pattern of glaucomatous optic disc cupping was investigated in 67 eyes of 67 primary open-angle glaucoma patients with early-to-moderate visual field loss and a wide range of intraocular pressure. We determined the position of the deepest point of the optic disc cup using the Rodenstock Analyzer. This position correlated significantly with intraocular pressure: the deepest point tended to be located below the center of the optic disc at high intraocular pressure and above the center at low intraocular pressure. There was no significant correlation between the position of the deepest cup point along the horizontal axis and intraocular pressure. The position of the deepest point of the cup also correlated significantly with the severity of glaucoma, albeit less strongly than with intraocular pressure: it tended to be in the inferior portion of the disc at an early stage of glaucoma and in the superior portion of the disc at a more advanced stage of glaucoma. Therefore, the inferior portion of the optic nerve head appears to be most yielding to changes of intraocular pressure. These findings are consistent with histologic evidence of the least connective tissue support in the inferoperipheral region of the lamina cribrosa and with greater prevalence of inferior rim loss and corresponding superior visual field defects in early to moderately advanced primary open-angle glaucoma patients. PMID- 1427139 TI - A laboratory evaluation of the Kowa laser flare-cell meter for the study of uveitis. AB - The Kowa FC-1000 laser flare-cell meter (LFCM) has been described as an instrument which will objectively quantify inflammation of the anterior chamber of the eye. We evaluated the LFCM using the intravenous endotoxin-induced uveitis (EIU) rabbit model of ocular inflammation. In vitro flare and cell calibration measurements utilizing bovine serum albumin (BSA) and latex particles, respectively, were also performed. A linear relationship between the flare measurements and BSA concentrations was noted. In addition, the time course of the LFCM flare count in EIU was comparable to previously published fluorophotometric data. However, the LFCM reported cells in the anterior chamber of the EIU rabbits despite negative cytology and histology results. The LFCM also recorded cells in BSA solutions which contained neither cells nor latex particles. Our results suggest that although the LFCM may be useful for evaluating flare, its cell measurements are not accurate in cases of severe uveitis. PMID- 1427140 TI - Are large optic nerve heads susceptible to glaucomatous damage at normal intraocular pressure? A three-dimensional study by laser scanning tomography. AB - To evaluate the effects of the presence of glaucomatous visual field defects and of intraocular pressure elevations on optic nerve head topography, we analyzed 148 left optic nerve heads of 148 patients using laser scanning tomography. The optic discs are classified according to computerized static perimetry and documented IOP readings: 101 discs show normal visual fields (36 normal discs, 22 ocular hypertensives, 28 normotensive glaucoma suspects and 15 ocular hypertensive glaucoma suspects), 47 discs (34 high-pressure glaucoma discs, 13 normal-tension glaucoma discs) demonstrate glaucomatous visual field damage. A two-way analysis of variance discloses significant differences (P < 0.01) between the groups of optic discs classified according to perimetry for most topometric parameters evaluated except for disc area. Classification according to documented IOP (cut off at 21 mmHg) results in larger disc areas in normotensive discs compared to hypertensive optic nerve heads in the study population. Results suggest that large discs may be susceptible to glaucomatous visual field damage at statistically normal IOP readings. PMID- 1427141 TI - Dysfunction of the blood-retina barrier following white light exposure. A tracer study with horseradish peroxidase and ferrous gluconate. AB - The aim of this investigation was to study the ultrastructural effects of white light on the retinas of pigmented rabbits. The retinas were exposed to white light (400-740 nm) at intensities between 65 and 140 mW/cm2 for 1 h. Two days after exposure, the increased leakage of fluorescein measured with vitreous fluorophotometry could be mimicked on electron microscopy by the tracers ferrous gluconate and horseradish peroxidase (HRP). In cases of minimal fluorescein leakage, traces of HRP were found in the basal folds of the retina pigment epithelium (RPE). No HRP was observed apical to the tight junctions of the RPE cells. When there was a great amount of fluorescein leakage, HRP completely filled the RPE cytoplasm, the extracellular spaces, and several cells in the neuroretina. It is concluded that after exposure to low intensities of white light, blood-retina barrier dysfunction may be due to disruption of the RPE basal fold membrane, leading to increased transcellular passage. The intact tight junctions suggest the under these circumstances intercellular leakage is not a component of BRB dysfunction. PMID- 1427142 TI - Late ultrastructural changes in the retina of the rat following low-dose X irradiation. AB - This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3-12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glial cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss. PMID- 1427143 TI - Nerve terminal degeneration in the rat iris observed following chronic topical 2% epinephrine and 0.1% dipivalyl epinephrine: a quantitative comparison of electron microscopic observations and tissue norepinephrine levels. AB - This is the first report of nerve terminal degeneration within the iris following topical dipivalyl epinephrine 0.1% treatment. A quantitative comparison of the effects of topically applied epinephrine 2%, dipivalyl epinephrine 0.1%, and placebo vehicle on the nerve terminals within the iris of a rat was made using electron microscopy and a catecholamine radioenzyme assay. Thirty-nine rats were divided into these 3 treatment groups and treated for 10 weeks, after which they were killed and studied. Both the epinephrine 2%- and dipivalyl epinephrine 0.1% treated groups showed greater nerve terminal degeneration compared with the placebo-treated group (P < 0.05). The epinephrine-treated group showed greater nerve terminal degeneration than the dipivalyl epinephrine-treated group. The clinical significance of these observations is unknown. It is impossible to decide whether these degenerative changes are related unavoidably to a desired therapeutic effect or to an undesirable, potentially avoidable, toxic side effect. PMID- 1427144 TI - Light and lithium effects in the rat retina: modification by the PAF antagonist BN 52021. AB - We tested the effect of an antagonist of platelet-activating factor (PAF), BN 52021, on both acute light-induced and light plus lithium-induced rod outer segment (ROS) lesions. Rats were fed lithium carbonate (2.6 g/kg chow) for 3 weeks. Half of the lithium-treated rats received BN 52021 (25 mg/kg) via gastric intubation prior to light exposure. Control and treated rats were exposed to 400 450 lux (measured at the eye level of the rats) of diffuse, white fluorescent light for 30 min, followed by 2 h of darkness and then decapitated. The eyes were removed and prepared for light and electron microscopic observation. The structural alterations of ROS were quantified from electron micrographs using a multifunctional computer image-analysis system. Our data show a significant reduction of ROS lesions by BN 52021, and this is most pronounced in light plus lithium-treated rats. Furthermore, in confirmation of previous studies, chronic lithium treatment significantly augmented light-elicited phagosome numbers, and BN 52021 reduced this effect. Our findings thus suggest that light and lithium may act via PAF responses in the rat retina. PMID- 1427145 TI - The effect of sodium iodate on the blood-retinal and blood-brain barriers. AB - Both active transport through and permeability of the blood-retinal barrier (BRB) are affected by sodium iodate, while the blood-brain barrier (BBB) is more resistant. We studied the effect of sodium iodate on facilitated diffusion through the two barriers. The retinal (RUI) and brain (BUI) uptake indices were determined for D-glucose and two neutral amino acids in normal and sodium iodate treated rats. The integrity of the barriers was estimated by RUI and BUI for L glucose and by measuring tissue uptake of L-glucose after an intravenous injection. We found that 30 mg/kg sodium iodate had no effect on transport through or permeability of the BBB, while 20 mg/kg significantly (P < 0.02) reduced transport of D-glucose, but not amino acids, through the BRB 1 h after injection. After 24 h both 20 mg/kg and 30 mg/kg sodium iodate caused a significant disruption of the BRB (P < 0.005 and P < 0.001, respectively). Thus, sodium iodate selectively affects the carrier for D-glucose in the BRB but not in the BBB. The presence of an epithelial part in the BRB, the retinal pigment epithelium, may explain the difference between the two barriers. PMID- 1427146 TI - Systemic candidiasis in babies with retinopathy of prematurity. AB - Fifteen premature babies developed systemic candidiasis during the administration of intravenous hyperalimentation in the Beilinson Neonatal Intensive Care Unit. Candida albicans was found in the blood cultures of all the babies and in the urine cultures of 66.7% of them. Repeated funduscopic examinations revealed no evidence of septic embolization in the retinal or choroidal circulation. It should be noted that acute retinopathy of prematurity (ROP) grade 2 or 3 was found in all the babies. PMID- 1427147 TI - Is there an association between optic disc drusen and angioid streaks? AB - We reviewed the color photographs and fluorescein angiograms of 110 subjects with angioid streaks. Evidence is presented for an association between drusen of the optic disc and angioid streaks. PMID- 1427148 TI - [Evaluation of the functional state of sailors during voyages in the arctic regions]. PMID- 1427149 TI - [The indicator system of the fetoplacental complex for evaluation of the condition of atmospheric air]. AB - Interrelationship between the structure-and-function changes in feto-placental complex and the worsening health status and development of children in arms effected by the chemical pollution of the ambient air was shown. Feto-placental changes expressed in decreasing of the protein and nucleic acid content and increasing of membrane permeability. PMID- 1427150 TI - [Toxicological characteristics of sebacic acid and the substantiation of its maximum permissible exposure level in atmospheric air]. AB - Average daily MAC of the sebacic acid in the ambient air established at the level of 0.05 mg/m3 (3-d class of hazard). Data of acute and chronic experiments were noted. PMID- 1427151 TI - [Effect of underwater community and domestic wastes on bacteriological characteristics of the coastal water in the north-west area of the Black Sea]. PMID- 1427152 TI - [Current status and tasks of sanitary-protozoological studies of drinking water (review of the literature)]. AB - Occurrences of giardiasis in the USA, Canada, Great Britain and other countries caused by drinking water were noted. Necessity of sanitary-and-protozoological inspection of the drinking water in the USSR was demonstrated. PMID- 1427153 TI - [Recreational load and bacteriological indicators of the quality of seawater]. PMID- 1427154 TI - [Standardization of anthropogenic pollution of seawater]. PMID- 1427156 TI - [Experimental substantiation of the maximum permissible exposure level of N methylformamide in reservoir water]. PMID- 1427155 TI - [Hygienic substantiation of standardization of the iron level in hot water of the central heating system in residential areas]. AB - Epicutaneous applications of the iron trivalence caused the sensibilization of mice. The effect depended on the temperature. PMID- 1427157 TI - [Effect of the insecticide "Sonet" on the microflora and biological activity of soil]. PMID- 1427158 TI - [Hygienic evaluation of working conditions in present-day production of welding electrodes]. AB - Complex of unhealthy factors in the welding electrodes production was estimated. The leading ones are the high level of the noise and high concentration of the manganese dioxide aerosol in air. Toxicochemistry of the action of these factors was discussed. PMID- 1427159 TI - [Effect of manganese on immunologic response of the body]. PMID- 1427160 TI - [Use of the "exposure level-body condition" relations for evaluation of the effects of complex atmospheric pollution]. AB - Criteria for the organism status arrangement in terms of environmental effects expression from adaptation to its break-down were worked up. The criteria may be used in developing of the hygienic standardization of environmental effects. PMID- 1427161 TI - [Status of the antioxidant systems in female workers in vegetable-growing hothouses]. PMID- 1427162 TI - [Immunologic status of subway workers]. PMID- 1427163 TI - [The role of refrigerators in spreading of bacteria of the genus Yersinia]. PMID- 1427164 TI - [Rationalization of calculations of nutritive value of food in laboratory control]. PMID- 1427165 TI - [A rapid method of evaluation of the effects of environmental factors on the degree of stress in human regulatory mechanisms]. AB - A basically new approach and a "Diagnoz" apparatus based on the one-stage recording of information processing rate and skin electric resistance were developed. The nervous system stress may be evaluated by the method in hygienic studies. PMID- 1427166 TI - [Combined effects of low doses of ionizing radiation and extreme factors of the Far North on the immune system (review of the literature)]. PMID- 1427167 TI - [Sanitary and chemical studies of polymer materials used in national economy]. PMID- 1427168 TI - [Study of hygienic properties of aminoplast KFA 5]. PMID- 1427169 TI - [Results of toxicological and hygienic studies of plastic articles for medical use]. PMID- 1427170 TI - [Modified effect of lead on the embryotoxicity of cadmium]. PMID- 1427171 TI - [Mathematical modeling of the changes in metabolic reactions in relation to environmental factors]. PMID- 1427172 TI - [Evaluation of the mutagenic activity of ammonium nitrate and dimethylamine salt of 2,4-dichlorophenoxyacetic acid]. PMID- 1427173 TI - [Experimental characteristics of allergenic properties of new dielectric and conductive pastes]. PMID- 1427174 TI - [Experience with teaching dietetics at the sanitary-hygienic department]. PMID- 1427176 TI - [History of organization of sanitary measures for the children of railroad workers]. PMID- 1427175 TI - [Allergic effects on the population of industrial air pollutants]. AB - Increasing of the allergization of the population in industrial regions caused by chemical pollution of the air was noted. Some changes in respiratory tract and blood count were reported also. PMID- 1427177 TI - [Use of the method of mathematical planning of an experiment for evaluation of harmful combined effects of xenobiotics on the general sanitary condition of water reservoirs]. PMID- 1427178 TI - [Use of the discriminant analysis for evaluation of the results of a toxicological experiment]. PMID- 1427179 TI - [Determining the coefficients of pesticide diffusion in the air]. PMID- 1427180 TI - [An improved method of quantitative analysis of mercury in washings and materials]. PMID- 1427181 TI - [Probability of reaching the reproductive and working age in the area of nuclear industry plants]. PMID- 1427182 TI - [A hygienic evaluation of the new flocculant polyhexamethyleneguanidine]. AB - Sanitary and toxicological study of some guanidine containing polymers was done. Moderate toxicity of the polymers and absence of any specific effects were noted. PMID- 1427183 TI - [An experimental validation of the MPEL for the Zharilek mixture and its component constituents]. AB - "Zharilek" preparation MAC in the water reservoirs was approved at the level of 0.01 mg/l. The preparation is referred to the 3rd class of hazard by the complex toxicological study. PMID- 1427184 TI - [Methods of water disinfection in swimming pools (a review)]. PMID- 1427185 TI - [Metal stearates--some aspects of their toxicodynamics]. PMID- 1427186 TI - [The effect of tetrachloroethylene on the genetic system of dry cleaning workers]. PMID- 1427187 TI - [The working conditions and health status of workers in natural gas recovery in the southern regions of the USSR]. PMID- 1427188 TI - [An analysis of the mutagenic activity of the chemical substances used in capron manufacture]. PMID- 1427189 TI - [The late effects of exposure to lead fluoride]. AB - Effect of lead fluoride dust on the micronuclear reticulocyte content in the bone marrow was shown. Some functional changes in the testicles and increase in the fetal death rate in exposure to 50 mg/m3 of lead fluoride dust were noted. PMID- 1427190 TI - [The diurnal energy expenditures of workers in the boiler-turbine shops of state regional electric power stations]. PMID- 1427191 TI - [The role of the social environment during the social psychological adaptation of adolescents]. PMID- 1427192 TI - [The role of the microsocial environment in the psychoprophylaxis of adolescent behavior]. PMID- 1427194 TI - [The social domestic risk factors for burns in children]. PMID- 1427193 TI - [The hygienic basis for using hardiness training procedures to promote the health of preschoolers]. PMID- 1427195 TI - [The evaluation of the work capacity of central nervous system function in 11- to 13-year-old pupils in a corrective class]. PMID- 1427196 TI - [The setting of hygienic standards for hexathiuram in the atmosphere]. PMID- 1427197 TI - [The nutritional prevention of postradiation effects]. AB - Radioprotective effects of vitamin complexes were shown. Author issued the possible mechanisms of the phenomena. PMID- 1427198 TI - [The sensitizing action of a high-frequency electromagnetic field]. PMID- 1427199 TI - [The validation of physiological standards for human color vision sensitivity]. PMID- 1427201 TI - [The significance of noninfectious allergens in living quarters]. PMID- 1427202 TI - [A toxicological hygienic evaluation of new additives for cattle feed]. PMID- 1427200 TI - [The hygienic evaluation of polymeric materials in prefabricated wood home construction]. PMID- 1427203 TI - [The prediction of the toxicity of the new plant-growth regulator fumar based on the results of a toxicokinetic study]. PMID- 1427205 TI - [The use of the dynamic-series method in epidemiological research]. PMID- 1427204 TI - [Water disinfection and water supply systems on sea-going ships (a review)]. PMID- 1427206 TI - [The use of the methods of multivariate statistical analysis in hygienic research]. PMID- 1427207 TI - [The effect of the air discharges from paper and pulp industry enterprises on population morbidity]. PMID- 1427208 TI - [The use of the elements of a new piecework pay system in medical institutions]. PMID- 1427209 TI - [A complex of methods for assessing body nonspecific resistance based on the immunological indices of the saliva]. PMID- 1427210 TI - [The use of biotesting for the hygienic evaluation of the toxicity of the ash and cinder from thermoelectric power stations]. PMID- 1427211 TI - [The metabolic aspects of crotonaldehyde]. PMID- 1427212 TI - [The genotoxic activity of nitrosodiethylamine studied by the micronucleus method in different organs of rats]. PMID- 1427213 TI - [Methodological approaches to a morphological analysis of the function of the mononuclear phagocyte system in exposure to chemical compounds]. PMID- 1427215 TI - [An experimental model for the study of the bactericidal action of UV radiation]. PMID- 1427214 TI - [A method for assessing the irritant action of chemical substances on the anterior eye segment]. PMID- 1427216 TI - [The behavior of xenobiotics in aqueous solutions exposed to gastric juice enzymes studied by an in vivo polarographic method]. PMID- 1427217 TI - [The atomic absorption determination of calcium, zinc, barium, lead and silver stearates in the air of a work area]. PMID- 1427218 TI - [The joint action of small doses of manganese and iron]. PMID- 1427219 TI - [Ideas of A. P. Dobroslavin in present-day community hygiene]. PMID- 1427220 TI - [Present day training of physicians of a prophylactic profile]. PMID- 1427221 TI - [A criteria system in comprehensive assessment of environmental chemical pollutant hazards]. PMID- 1427222 TI - [Hygienic standardization of the water quality: build-up and prospects]. PMID- 1427223 TI - [Estimation of the distribution of experimental animals with different status exposed to a complex of chemical environmental factors]. PMID- 1427224 TI - [A. P. Dobroslavin's works in the area of the development of hygienic measures for control of epidemics in the light of present-day advances in medical science]. PMID- 1427225 TI - [Development of A. P. Dobroslavin's ideas concerning the questions of environmental hygiene]. PMID- 1427226 TI - [Development of scientific trends in soil hygiene]. PMID- 1427227 TI - [Development of morphofunctional studies in hygiene (from works of A. P. Dobroslavin to our times]. PMID- 1427228 TI - [Biochemical aspects of pre-nosological diagnosis of the effects of chemical environmental pollution]. PMID- 1427229 TI - [Experimental model of exogenous allergic alveolitis]. PMID- 1427230 TI - [Problems of analytical control in environmental health]. PMID- 1427231 TI - [Current aims in the improvement of the installment and quality control of water supply]. PMID- 1427232 TI - [Development of A. P. Dobroslavin's ideas in the organization of military health measures]. PMID- 1427234 TI - [Disinfection and purification of drinking water by portable autonomic water purifiers of combined action]. PMID- 1427233 TI - [A. P. Dobroslavin, the founder of hygiene in our country]. PMID- 1427235 TI - [Hygiene in the planning of a system of environment quality management]. PMID- 1427236 TI - [Effects of environmental pollution in the area of a chromium-processing plant on the health status of population]. PMID- 1427237 TI - [Systemic studies and developments in hygiene]. PMID- 1427238 TI - [New medical disinfectants]. PMID- 1427239 TI - [Toxicokinetics of borates and borides after a single exposure]. PMID- 1427240 TI - [Comparative toxicity of pyridine derivative isomers]. PMID- 1427241 TI - [Effects of decis on the state of the skin and hairy integument]. PMID- 1427242 TI - [Aleksei Petrovich Dobroslavin: a forefather of military hygiene in our country]. PMID- 1427243 TI - "Caregiving" to depressed older persons: a relevant concept? PMID- 1427244 TI - Impact of self-management education on the functional health status of older adults with heart disease. AB - This paper presents findings from the evaluation of a self-management education program based on self-regulation principles. Older men and women (N = 324) were randomly assigned to program and control groups. Outcomes were measured using the Sickness Impact Profile. Twelve months following baseline data collection, psychosocial functioning of program participants was significantly better than that of controls. Different program effects were noted when results were analyzed by participant gender. PMID- 1427245 TI - Exercise beliefs and behaviors among older employees: a health promotion trial. AB - This health promotion trial included university faculty and staff aged 50 to 69 who had completed a health risk screening. Predictors of intention to exercise were education, gender, self-efficacy, outcome expectancy, perceived barriers, and baseline exercise frequency. Baseline exercise frequency was the only predictor of exercise behavior 1 year later. PMID- 1427246 TI - Attempts to prevent falls and injury: a prospective community study. AB - At 16 senior centers, we studied the effectiveness of exercise and cognitive behavioral programs, compared with a discussion control program, in reducing falls and injuries among 230 older adults. After 1 year of the programs, we observed no significant difference in time to first fall. Even though a relatively high percentage (38.6%) suffered at least one fall, only 7.8% of these community-residing elderly required medical attention. Secondary outcome measures such as strength, balance, fear of falling, and perceived health did not significantly change. PMID- 1427247 TI - Housing emergencies and the etiology of homelessness among the urban elderly. AB - This research examined factors that lead to homelessness and shelter placement of seniors. A purposive sample of 475 aged clients was selected randomly from the files of a citywide emergency service program, 45% of whom were found to have had serious housing-related problems. A subsample of 115 housing problem cases was investigated, including persons who had needed emergency shelter or temporary housing or been living in deteriorated housing. Assessment data from the OARS instrument and open-ended housing history questions were analyzed. Homelessness was found to be significantly associated with low income, dementia, living alone, and an unstable residential history. PMID- 1427248 TI - Project rescue: serving the homeless and marginally housed elderly. AB - The authors describe the engagement techniques and service components of a program for homeless and marginally housed elderly. On follow-up evaluation of 132 people, clients averaged three favorable outcomes (maximum = 7). Service delivery was conceptualized as a three-stage process based on the differential effects that variables had at each stage. The strongest predictors of outcome were number of service encounters, type of presenting problem, and perceived level of social support. PMID- 1427249 TI - Did tax reform hurt the elderly? AB - Federal and state income tax reform increased aggregate federal tax payments of elderly taxpayers by just over 5% and their aggregate state taxes by about 6%. However, the entire increase is accounted for by the elderly in the top income decile. The mean change in total income taxes paid by the elderly was $135, but the median increase was zero because most older persons paid no federal or state income tax before or after tax reform. The overall effect of tax reform was a slight shift in income tax burdens from the nonelderly to the elderly reversing a trend dating from the late 1970s. PMID- 1427250 TI - Economic rationality, the affordability of private long-term care insurance, and the role for public policy. AB - This study uses data from the 1984 panel of the Survey of Income and Program Participation (SIPP) of the U.S. Bureau of the Census to develop new estimates of the potential market for private long-term care insurance. It found that this market is potentially significant--especially among individuals in the 65-69 age group who are willing to spend up to 50% of their discretionary income on such insurance--but considerably lower than previous estimates, such as those of Cohen and colleagues (1987). PMID- 1427251 TI - Difficulties and rewards in family care of the depressed older adult. AB - Spouse and adult child caregivers of older adults with major depressive disorder (N = 150) were asked what was most difficult and most rewarding about providing assistance to their relatives. Content analysis of their responses revealed seven areas of difficulty and three areas of reward. Difficulties and rewards were selectively associated with the caregiver's identity, patient clinical characteristics, and caregiver emotional adjustment. Caregiver perceived family difficulties and emotional difficulties were associated with the course of patient psychiatric illness over 1 year. PMID- 1427252 TI - Severe family violence and Alzheimer's disease: prevalence and risk factors. AB - This study describes the prevalence of violence and the putative risk factors for violence in 184 Alzheimer patients and their primary caregivers living in the community. Analysis of the severe violence subscale of the Conflict Tactics Scale indicated that 15.8% of patients had been violent in the year since diagnosis. A total of 5.4% of caregivers reported being violent toward the patient. The overall prevalence of violence was 17.4%. The variables most associated with violence were caregiver depression and living arrangement. PMID- 1427253 TI - Gender differences in caregiving: fact or artifact? AB - This study applies meta-analysis techniques to the results of 14 descriptive studies of gender differences in caregiving to determine the size and significance of gender differences in caregiving stressors (level of elder impairment and level and type of task involvement) and in caregiver burden. There were essentially no significant gender differences in functional impairment of the frail care recipient, total caregiver involvement in care, or in money management tasks. Female caregivers were more likely to carry out personal care and household tasks and more likely to report greater burden. Given the relatively small size of the effects found, we conclude that future research should focus on the part that gender-role explanations play in assigning meaning to caregiving behaviors. PMID- 1427254 TI - Adjustment among different age and ethnic groups of Indochinese in the United States. AB - This study examines adjustment among different age and ethnic groups of Indochinese refugees in the United States. The data came from a nationwide probability sample of 3,414 respondents aged 20 or older. Respondents are divided into four age groups (20-29, 30-39, 40-54, and 55 and older). Ordinary least squares regression analysis revealed that education, occupational status, urban/rural location in the country of origin, English language ability, financial problems, gender, age, and length of residence in the U.S. had statistically significant relationships with adjustment in different age and ethnic groups. PMID- 1427255 TI - Parental dependence and filial responsibility in the nineteenth century: Hial Hawley and Emily Hawley Gillespie, 1884-1885. AB - This paper examines diaries written by an Iowa farm woman and her daughter in the 1880s that focus on care of the former's father. It highlights the problems intergenerational living arrangements could produce in the 19th century. In addition, it examines three general themes: the impact on adult children of financial responsibility for elderly parents, the responses of elderly people to structures of subordination, and the significance of hierarchies of gender as well as generation. PMID- 1427257 TI - Blood pressure measurements in the nursing home: are they accurate? AB - To examine the accuracy of blood pressure (BP) measurements in the nursing home, a trained observer (physician) and nursing home staff (NHS) measured BP for 146 nursing home residents on two separate occasions. Using the physician as the reference standard for measuring BP, the NHS: 1) significantly underestimated systolic BP; 2) significantly overestimated diastolic BP; and 3) had a high frequency of terminal digit preference for zero. These errors resulted in the NHS misclassifying hypertension in 21% of patients. PMID- 1427256 TI - Alternative sources of social support and their impacts on institutional risk. AB - We examined the direct and buffering effects of different dimensions of social support on the risk of being institutionalized over a 2-year period. Multivariate analyses indicated that specific aspects of social support, such as having a spouse or adult child caregiver, or having a caregiving relationship of at least 3 years' duration, moderated the impact of one type of stress (being highly dependent on others for care) on the risk of entering a nursing home. Networks that included a paid provider modestly offset the impact that multiple IADL impairments had on being admitted at least once to a nursing home. PMID- 1427258 TI - Impact on caregivers of supporting urinary function in noninstitutionalized, chronically ill seniors. AB - In a multivariate study of 148 caregivers of chronically ill older persons, 22% of those caring for a continent senior reported that maintaining continence was a burden, and 75% of caregivers of incontinent seniors reported it as burdensome. The burden of maintaining urinary function was associated with lack of social support, time spent providing care, and care receiver's immobility. Caregivers' depressive symptoms were associated with perceived burden from providing care for urinary function, a confused care receiver, and post-stroke support. PMID- 1427259 TI - Physicians' acceptance of behavioral treatments and pharmacotherapy for behavioral disturbances in older adults. AB - In response to growing interest in employing behavioral treatments and environmental modification for behavioral disturbances in older adults, we employed vignette methodology to examine physicians' acceptance of two behavioral treatments and haloperidol using Kazdin's Treatment Evaluation Inventory. Physicians assigned the highest acceptability ratings to the behavioral treatments and the lowest ratings to haloperidol. The patient's cognitive capacity, living situation (nursing home vs. community), and the type of behavior problem mediated treatment acceptability ratings. PMID- 1427260 TI - Enhancing the self-esteem of selected male nursing home residents. AB - This study investigated treatment procedures for enhancing the self-esteem of older adult male nursing home residents. Twenty-one subjects were assigned randomly to either a control group meeting to discuss current news events or an experimental group receiving the intervention. Self-esteem significantly increased for the experimental subjects but not before they experienced a significant decrease in feelings of self-worth. The midtreatment observation of the dependent variable was a vital factor in determining the curvilinear relationship between time and the protocol. PMID- 1427261 TI - Integrative outpatient group therapy for discharged elderly psychiatric inpatients. PMID- 1427262 TI - Transportation as outreach, driver as mental health worker. AB - Case finding and early detection and referral of elderly persons with mental problems can be accomplished by trained and supervised drivers as part of a transportation service. Increased access to community programs and services as a result of provided transportation helped clients maintain their independence and self-esteem. PMID- 1427263 TI - Public opinion versus public rhetoric. PMID- 1427264 TI - MDS data should be used for research. PMID- 1427266 TI - Qualitative research comes of age in gerontology. PMID- 1427265 TI - Animal studies are teaching us about aging. PMID- 1427267 TI - Positive ageism? PMID- 1427268 TI - Time to abandon "caregiving"? A reply to Parmelee and Katz. PMID- 1427269 TI - Voting behavior among low-income black elderly: a multielection perspective. AB - We examined voting behavior among 370 low-income older African-American citizens who reside in New Orleans by assessing the impact of various predictors on electoral participation in a series of seven elections. Elders who were active in their community, with a strong sense of citizen duty, who identified themselves as strong Democrats, and with higher levels of education were more likely to vote. PMID- 1427270 TI - The political behavior of older American blacks. AB - Using a subsample of the National Opinion Research Center's 1987 General Social Survey, this study examined three competing explanations for the political behavior of older black Americans (n = 157, 55 and older). The socioeconomic model was a good predictor of political behavior; ethnic community theory and the empowerment model were, in varying degrees, predictors of alienation but not of political interest or activity. Some comparisons were made between older black Americans, younger blacks, and older and younger whites. PMID- 1427271 TI - Older voters and the 1992 presidential election. AB - At the core of the so-called "generational equity" construct is the notion that older persons exercise self-interested political power. This article examines what we know about one element of the politics of aging--the voting behavior of older persons in recent presidential elections--and suggests areas of research on the 1992 election that may tell us something about how far, and how soon, proponents of generational equity will be able to move toward dismantling policies that benefit older people. PMID- 1427272 TI - Women as family caregivers: why do they care? AB - This study was based on in-depth qualitative interviews with 40 francophone Quebecois family caregivers of frail elderly or mentally ill relatives and focused on the caregiving relation rather than on the specificities of aging and mental illness. Fourteen factors (love, guilt and duty, women's social identity built around caring, absence of appropriate public or private care alternatives, women's socioeconomic dependence, etc.) emerged from an analysis of informants' accounts of how they came to be the primary caregiver. Data indicate that analyses attempting to understand women's caregiving must take into account the sexual division of labor, its reinforcement through social policy, and how women internalize ideas and norms regarding appropriate gender-role behavior. PMID- 1427273 TI - A path not taken: a cultural analysis of regrets and childlessness in the lives of older women. AB - This paper explores regrets about childlessness in 90 older women interviewed using qualitative methods. Regrets were discussed in the context of the changing meaning of childlessness over the life course. We found that issues of regret are situated in a cultural system that renders childless women marginal. We argue that regrets should be understood in a wider cultural context that incorporates the cultural construction of the self over time. PMID- 1427274 TI - The role of animal models in meeting the gerontologic challenge of the 21st century. AB - Animal models play an important role in our quest to understand aging and develop interventions needed for the gerontologic challenge of the 21st century. Results from studies using the dietary restriction rodent model are presented as an example. Dietary restriction slows aging by inhibiting primary aging processes, by enhancing broadly protective mechanisms, or by both. Further study should identify the mechanisms and yield a data base for development of interventions. A threat to attaining these yields is the growing opposition of some to this use of animals. PMID- 1427275 TI - High-risk profiles for nursing home admission. AB - A statewide probability sample of 1,625 Massachusetts elderly was studied prospectively over a decade to identify risk profiles for long-term care (LTC) institutionalization. Previous admission to a LTC institution, age, basic ADL disability, and restricted outside mobility were the strongest individual predictors of institutionalization. Examining profiles of risk factors dramatically increased the ability to predict 10-year risk of admission. PMID- 1427276 TI - Functional limitations among home health care users in the National Health Interview Survey Supplement on Aging. AB - A case-control study compared home health care (HHC) users from the 1984 Supplement on Aging to users of other community services and of no community service, matched on age and gender. Examination of specific activities of daily living (ADLs), instrumental activities of daily living (IADLs), and sociodemographic variables showed that HHC users were significantly more limited than controls in every ADL and IADL. In multivariate analyses, HHC use was significantly associated with three ADLs (dressing, going outside, bathing), two IADLs (shopping, heavy housework), and poor health status. PMID- 1427277 TI - Conflict in Alzheimer's caregiving families: its dimensions and consequences. AB - This paper views conflict in Alzheimer's caregiving families as a multidimensional construct. Three conceptually distinct dimensions of family conflict are described and examined in relation to depression and anger. Regression analyses indicate that conflicts involving family members' attitudes and actions toward the caregiver are associated with increased risk for depression among caregivers, whereas conflicts stemming from family members' attitudes and behaviors toward the patient are most likely to result in anger. Self-concepts and normative expectations are implicated as key explanatory variables. PMID- 1427278 TI - Caregiving: role engulfment and the loss of self. AB - "Loss of self" was examined in a sample of spouses and adult children caring for a relative with Alzheimer's disease. Defined as a loss of identity that comes about as a result of engulfment in the caregiver role, it was found to be more common among spouses, females, and younger caregivers. Limited social contact and lack of social roles outside that of caregiver were found to be related to greater loss of self. It is associated with lower self-esteem and mastery and with greater depressive symptomatology. PMID- 1427279 TI - Institutional placement: phases of the transition. AB - The consequences of institutionalization were examined for a sample of caregivers of dementia patients. Consistent with the stress process model, institutionalization was hypothesized to have a large impact on the primary effects of caregiving and lesser influence on secondary effects and well-being. Following placement, relatives experienced relief from primary effects of caregiving (e.g., feelings of overload and tension) and improved well-being, whereas other indicators of stress remained unchanged. PMID- 1427280 TI - The bereaved caregiver: a prospective study of changes in well-being. AB - This study analyzes short-term bereavement adaptation among caregivers to spouses or parents with a progressive dementia, assessing changes in depression, mastery, overload, and guilt to examine the impact of bereavement on caregivers, and the characteristics of caregiver experience that affect bereavement adaptation. The bereavement group, as compared with active caregivers, dropped substantially in overload and increased in mastery and guilt. Depression showed a curvilinear trend, declining from the time of death and then rising to preloss levels by the end of the year. Caregiver stressors, baseline adaptation, relationship difficulties, and psychological preparation were all related to changes in well being. PMID- 1427281 TI - A room of one's own: the SRO and the single elderly. AB - A survey of 485 single-room occupancy housing (SRO) residents in New York City found elderly residents strongly preferred to remain in centrally located neighborhoods where apartment housing was beyond their means; did not wish to share a housing unit; and had little confidence that they could find acceptable housing if they lost their present unit. For many elderly residents, SROs meet needs not easily met by available alternatives. Results suggest the need to maintain this housing option for older persons and replace losses that have accompanied gentrification in many central city areas. PMID- 1427282 TI - Employer-sponsored postretirement health benefits: not your mother's medigap plan. AB - Using nationally representative data, we report the prevalence of retiree health insurance as a fringe benefit in private and public settings, and take an in depth look at its content. We examine how it coordinates with Medicare to characterize the "total insurance" of beneficiaries who hold these supplements. Retiree health coverage is now widespread and typical benefits are far more generous than those found in medigap policies, the other major type of Medicare supplement. When a typical retiree plan is overlaid on Medicare, the resulting total insurance benefits are more generous than those held by either the working nonelderly or beneficiaries with a medigap supplement. PMID- 1427283 TI - Homebound Learning Opportunities: reaching out to older shut-ins and their caregivers. AB - Homebound Learning Opportunities (HLO) represents an innovative health promotion and educational outreach service for homebound older adults and their caregivers. It provides over 125 topics for individualized learning programs delivered to participants in their own places of residence, an audiovisual lending library, educational television programming, and a peer counseling service. Shut-ins are recruited as instructors and as participants in service projects that benefit the greater community. Preliminary assessments reveal high levels of participation and satisfaction with the program. PMID- 1427284 TI - [Hysteroscopy in infertility]. AB - An evaluation of hysteroscopy as complementary study of the sterile couple, was carried out; the hysteroscopic findings were compared with laparoscopic findings, and with Hysterosalpingography (HSG); it was a longitudinal, retrospective study of 20 patients. In the obstetrical antecedents there were 58 gestations, 50 of which ended in abortion. From de five normal cavities by HSG four were for hysteroscopy. As compared with hysteroscopy, HSG detected only 75% of submucous myomas, 85% of walls, 100% of IUD's fragments and of cervical incompetences. In the case of sinechias it was confirmed by hysteroscopy 80% of the diagnosed by HSG. The only case of endometrial polyp was detected by hysteroscopy. Surgical procedures were carried out in 40%, with complications in 16.6%. It was conclude that hysteroscopy is a complementary method, but necessary, in the study of the sterile couple with the possibility at the same time of being a therapeutic method. PMID- 1427285 TI - [Experience with the management of endometritis in the Instituto Nacional de Perinatalogia]. AB - Endometritis is the most frequent infectious complication of the puerperal period; with the objective to know the clinical characteristics, etiology and evolution of this disease we did a retrospective study of the endometritis cases among the patients of the Instituto Nacional de Perinatologia (INPer) from January 1st, 1990 to May 31, 1991. During the revision period were diagnosed 120 cases, but we were able to examine only 90. In the 90% the resolution of the pregnancy was by means of caesarean. A 24.4% of the patients had premature rupture of the membranes. The 10% had diagnose of chorioamniotis. The latency period to develop postpartum endometritis was 120 +/- 66 hours, and post caesarean 56 +/- 30 hours (p = 0.001). The symptom most frequent were fever (100), foul-smelling lochia (61.1%) and uterine tenderness (60%). The infection was polymicrobial, being the microorganisms most frequent isolated Staphylococcus coagulase negative, Escherichia coli and Peptostreptococcus. A 3.3% developed pelvi-peritonitis. One patient died. PMID- 1427286 TI - [Simultaneous identification of the nucleolar organizing regions and G bands in obstetrical cytogenetic studies]. AB - An improvement of the silver-staining method of the nucleolus organizer region with simultaneous trypsin-Giemsa-banding is described. The combined demonstration of such regions (which express the transcriptive activity of ribosomal ribonucleic acid genes) and the precise identification of chromosomes, particularly acrocentric chromosomes, should be of value in the investigation of parents with spontaneous abortion in whom abnormal acrocentric chromosomes are often encountered. PMID- 1427287 TI - [Pregnancy in adolescents. Complications, birth weight, somatometry of the newborn and Apgar score, comparison with the general population]. AB - The objective of this study was to compare pregnancy evolution, newborn's weight, its somatometry and Apgar's qualification of teenagers and the general population in a community where the socio-economic factor is similar among those two groups. Three hundred and two pregnancies in teenagers were analyzed, 69 of 12-15 years and 233 of 16-17 years at the time of pregnancy, against a control group of 304 pregnant patients of 18-39 years. It was a prospective, comparative, longitudinal study. Average age at the first delivery of the 606 patients was 18.1 years. There were no significant difference among the groups as to occupation. There was not significant difference among the three groups as to pre-natal control, weeks of gestation incidence of threatening abortion, toxemia, bleeding of the second half of pregnancy, premature rupture of membranes, proportion of deliveries and cesarean sections, as well as forceps application and newborns' sex. The most common indications of cesarean section in teenagers were CPD and acute fetal suffering, in the control group were CPD and pelvic presentation. There was significant difference comparing the weight, Apgar qualification at one minute and at three minutes in the 16-17 years group, and older of 18 years being greatest in the last group. There was significant difference in size, cephalic perimeter, thoracic perimeter and PC/pa ratio among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427288 TI - [Dermatomyositis and adenosquamous carcinoma of the ovary. Report of a case]. AB - A case of adenosquamous ovarian carcinoma in a 50 years old female is reported. The patient had marked improvement of her symptoms after resection of the tumor and chemotherapy. The knowledge of this association forces to rule out an ovarian carcinoma. PMID- 1427289 TI - [Molecular systems in cellular interactions. I. Fertilization iin mammals]. AB - Multicellular organisms require diverse mechanisms of cellular recognition in order to work integrally. In the present paper we consider the molecular mechanisms for cell recognition and cell adhesion on fertilization of mammalian egg. Several surface proteins of spermatozoa (galactosyl transferase, proteases, glycosidases and lectins), recognize and bind zona pellucida glycoproteins of egg, a necessary condition prior to fertilization. PMID- 1427290 TI - [The critical period in natural fertility]. AB - In order to learn the natural expectancy period of first pregnancy as well as the influences of some biosocial variables, a clinical-retrospective study was performed within 1120 gravida I women. All of them attended the major institutes of health care in Mexico City (IMSS, ISSSTE, SS and DDF). Data were obtained by means of predetermined questions from subjects after the first postpartum hours. None of them had previously used any contraceptive method. Results showed age at the first pregnancy: 21.6 +/- 3.8 (years); gestational interval 22.1 +/- 19.9 (months) and a 67% achievement rate the following twelve months of sexual activity. Eutocia was seen in 54% of these population and significant linear correlation was attained between age of the patient and the gestational interval. It seems that this is the first information regarding the fertility critical period within our society. PMID- 1427291 TI - [The allergologic status of vegetable growers in hothouses]. AB - Studies of the main factors causing allergic diseases, level and structure of allergic morbidity proved the prevalence of contact allergic dermatitis and urticaria among hot-house plant workers. Opportunistic bacteria and Streptococcus pyogenes were found to play an important role in sensitization of vegetable growers. The rational employment of subjects suffering from allergic diseases is recommended. PMID- 1427292 TI - [Dermatomycoses in workers in enterprises of the microbiological industry]. AB - Mycologic examination of 54 patients with clinical manifestations of dermatomycosis, engaged in glucose oxidase and catalase production has found a producer fungus, Penicillium vitale in 31 (38%); 3 out of 37 people contacting with producers of glucamylase and pectofetidine appeared to be infected by Aspergillus awamori (1.1%) and Aspergillus foetidus (1.1%), respectively. The producers were isolated from the skin of 40 (16.44%) out of 243 workers having no clinical signs of dermatomycosis, mainly in drying, granulating and microbiology lab workers. Dermatophytes (50.9%), yeast fungi (1.8%) and other agents were isolated from the skin of patients with clinical manifestations of dermatomycoses. Age and sex of personnel, length of service and infectious contamination of technological premises were found to influence the skin disorder caused by dermatophytes in combination with producer fungi. Prophylactic measures to prevent the contamination of air and skin by producer fungi and their metabolite are to be developed. PMID- 1427293 TI - [The cytokinetics of the bronchoalveolar lavage fluid from workers in silicosis hazardous jobs]. AB - Cytogram of pulmonary lavage fluid was studied in 50 workers al risk of developing silicosis. Workers with long length of service showing no radiographic signs of silicosis had normal cytogram of pulmonary lavage fluid, except for slightly increased neutrophil counts. Cytogram of patients with first recognized silicosis were characterized by elevated lymphocyte count. Neutrophil level increased in chronic silicosis. Cytogram of pulmonary lavage fluid is considered valuable for the diagnosis and prognosis. PMID- 1427294 TI - [The lipid peroxidation processes and the mono-oxygenase system in workers exposed to asbestos dust]. PMID- 1427295 TI - [Data from an in-depth medical examination of workers at the Astrakhan Gas Condensate Plant]. PMID- 1427296 TI - [Lipid peroxidation and thrombocyte aggregation in vibration disease]. AB - A three-fold increased level of malonic dialdehyde was found in platelets of patients suffering from the first stage of vibration disease, exposed to local vibration. The changes of the fermentative and nonfermentative lipid peroxidation (LPO) were: increased accumulation of malonic dialdehyde (by 2.5 times in ascorbate-dependent LPO and by 2.6 times in NADRH-dependent LPO). Patients with peripheral vasomotor dystonia of the upper limbs combined with vasomotor spasms of the fingers showed NADPH-dependent and ascorbate-dependent LPO respectively 41% and 29% more activated than in patients having no vasomotor spasms. In patient with vibration disease antioxidant activity was reduced by 39% on average, platelet aggregation, both spontaneous and induced by epinephrine, aggristine or adenosinediphosphoric acid, was increased. Platelet hyperaggregation in vibration disease may be caused by stimulated LPO in platelets, amassed end toxic product of LPO, decreased antioxidant activity. PMID- 1427297 TI - [Lipid peroxidation in the liver microsomes--a sensitive link in body exposure to vat dyes]. AB - Experiments on male white rats showed that the soluble forms of vat dyes such as red brown 'G' (RBG) and bright green 'G' (BGG) delivered into the stomach in a toxic dose (1 g/kg) activate lipid peroxidation (LPO) in liver microsomes. Chronically inhaled dyes hasten of slow down some LPO stages, the changes depending on the concentration, duration of exposure and chemical structure of a compound. Soluble vat dye RBG increases LPO in concentration 5 mg/m3 whereas RBG shows antioxidant action in high and low concentrations. PMID- 1427298 TI - [The stability of the hearing function as a problem of otoergonomics]. AB - Hearing stability was measured by the method using physiologic dependence: the better were body possibilities to resist the unfavourable effect of acoustic environment, the higher was the tolerance threshold. Hearing stability measured by the suggested method appeared to be an individual stable characteristic that can be predicted. PMID- 1427299 TI - [Scientific and technical progress and the problems of protecting the health of workers in water transport]. AB - The influence of scientific and technological progress on the work and life of man in the world ocean is analysed. The main results of investigations and practical solutions are described in details. The drawbacks in the research of some aspects of the problem are shown and the objects of further investigations are outlined. PMID- 1427300 TI - [The pathogenesis of trichloroethylene poisoning]. AB - Basing on the results of original clinical and experimental studies, as well as on medical literature data, the contributors proposed a hypothesis of the toxic action of trichloroethylene. It was attempted to prove that the trigger links of trichloroethylene intoxications were the energy exchange disorders caused by the nonspecific membranotoxic actions of the substance's molecules and their metabolites, as well as the extra consumption of energy by the metabolic processing of the poison. Involvement of adaptational reactions, such as the catecholamines' discharge, under the conditions of the damaged metabolic system, decreased the cell's potential and aggravated the severity of intoxications. PMID- 1427301 TI - [Data on the hygienic regulation of benzanthrone-based vat dyes in the air of a work area]. AB - With regard to acute toxicity, the cubosols are attributed to the non-cumulative compounds of low toxicity. Acute inhalation exposure threshold for cubosol "Bright green" is over 140 mg/m3. Subacute poisonings developed following intragastric administrations in concentrations 1 g/kg for 30 days, and were characterized by polymorphism of the signs. Revealed were delayed body mass increment in the laboratory animals, changes in peripheral blood and hepatorenal morphology and function. PMID- 1427302 TI - [The use of a thin-layer chromatographic method for measuring the concentrations of mixtures of the dyes scarlet 2G and black 2K in the air of a work area]. AB - Scarlet 2G and black 2K dyes were divided and measured by thin-layer chromatography with mixture of acetone and toluene (3:4) used as an eluent for dividing scarlet 2G and a mixture of chloroform, benzene and acetone (3:2:1) for eluting black 2K. The method permits the detection of the aforesaid dyes in the air of working area at the level of 0.5 MAC in the presence of admixtures. PMID- 1427303 TI - [The characteristics of the health and hygienic conditions of working in the manufacture of thioindigo-based vat dyes]. PMID- 1427304 TI - [The toxicological evaluation of dust from the ion-exchange fiber VION AN-1]. PMID- 1427305 TI - [The mechanism of the neurotropic action of emulsifying flushing fluids used in drilling]. PMID- 1427306 TI - [The structural-biochemical characteristics of the glycoconjugates of alveolar macrophages under the action of quartz and coal dusts]. PMID- 1427307 TI - [The problems of protecting the health of the population of industrial-area complexes]. PMID- 1427308 TI - [The industrial environment in the electric-furnace steel smelting, converter and open-hearth furnace methods of manufacturing manganese-alloyed steels]. AB - Inspection of the environment in manganese-alloyed steel production showed inadequate hygienic conditions of the technological processes employed. Air was more polluted by manganese oxides during the oxygen-converter process though their highest concentrations, 38 times exceeding the MAS, appeared during the casting of steel. An electric furnace coated by dust-noise-proof material and gas cleaning is preferable from a hygienic point of view. The influence of unfavourable microclimate, intensive infrared irradiation and loud noise on workers necessitates automation and mechanization of the process in order to improve the working conditions. PMID- 1427309 TI - [The effect of industrial factors on specific functions and the course of pregnancy and labor in workers of the Orgsintez Manufacturing Association]. AB - Women engaged in the production of chlorine, divinyl and propylene oxide are exposed during the working shift to unfavourable occupational factors: gas, dust, noise, emotional and physical stress, inadequate microclimate. All that disorders the specific functions and health status. Diseases in women working for 'Orgsintez' enterprise are closely connected with the length of service. Occupational factors of this chemical enterprise influence the course of pregnancy and labor, condition of fetus and newborn. PMID- 1427310 TI - [Methodological approaches to establishing the true and expected levels of occupational morbidity on the scale of a branch (sub-branch) of the economy (exemplified by the construction materials industry)]. PMID- 1427312 TI - [The central hemodynamics of participants in the cleanup of the sequelae of the accident at the Chernobyl Atomic Electric Power Station 4 years after the accident]. AB - Investigations of the central haemodynamics and myocardial contractility in 73 men, who took part in repairing after the Chernobyl accident in 1986, in 4 years after the accident have shown the hyperkinetic type of circulation in 60.2%, eukinetic in 23.2%, hypokinetic in 15.6% of the examinees. Such changes of the central haemodynamics, increased frequency of the hyperkinetic type are due to the regulatory disorders decreasing the vascular tone in the major and minor circles, amplifying the venous return to heart and increasing the myocardial contractility. PMID- 1427311 TI - [Industrial hygiene problems in reclamation constriction operations]. AB - Workers engaged in reclamation construction are exposed to dust and chemical agents, appearing in the air during the work. Vibration, noise, meteorologic conditions overmatch the normal parameters. Immunologic status is changed, transitory disablement incidence is high, occupational diseases occur. Hygienic measures for this population are recommended and put into practice. PMID- 1427313 TI - [The evaluation of the work regimens of miners in the gold-extracting placers of the north]. AB - Results of field physiologic and hygienic investigations of borer's work schedule during the subterranean gold extraction in the Chukot Range [correction of Chukotka] are presented. Methods and models of rational work schedule in conditions of the extreme north are suggested based on the dose approach. PMID- 1427314 TI - [A comprehensive assessment of the working conditions for workers in vibration hazardous jobs]. AB - Comprehensive evaluation of work conditions of workers of different occupational groups (bulldozer, excavator and boring machine operators, embroideresses) helped create a new parameter of occupation harmfulness evaluation: mean arithmetic value and root-mean-square digression. The main parameters of transitory disablement morbidity were found connected with the integral parameter of harmful environmental factors, which helped define the morbidity increase per 1 harmfulness grade for men and women and predict the morbidity levels of workers depending on their work conditions. PMID- 1427315 TI - [The criterial approach to the diagnosis of changes in the osteoarticular apparatus of persons in vibration-hazardous jobs]. AB - A criterial approach to the diagnosis of the skeletal system changes in individuals exposed to industrial vibration, involving the use of the X-ray diagnostic criteria (gerontologic, manual, vertebral) and the criterion based on the absorbed dose of vibration energy (exposure criterion) together with the data on the vibration disease manifestations (clinical criterion), makes it possible to estimate the risk of vibration disease. PMID- 1427316 TI - [The working conditions and morbidity with temporary loss of work capacity for those engaged in the manufacture of household chemical preparations]. AB - Workers engaged in production of household chemical goods (paints, synthetic detergents, aerosols) are exposed to harmful factors (noise levels higher than the maximal allowable ones, concentration of chemical agents in the air surpassing the MACs). Such work conditions are estimated as unfavourable according to the hygienic classification. The total morbidity and some nosologic forms (respiratory, digestive, locomotor systems and skin) are growing in number especially in workers of aerosol production. Statistic analysis revealed that the length of service was directly related to the level of total morbidity and the incidence of gastrointestinal diseases in the workers engaged in manufacture of household chemical goods. PMID- 1427317 TI - [The use of toxicometric information in developing the scientific and technical documentation for chemical production]. PMID- 1427318 TI - [The characteristics of the physiological functions and the biological age of the operators of metal spray guns for the gas-heat application of coatings]. PMID- 1427319 TI - [Magnesium sulfate as an industrial poison]. AB - The article provides information on the hygienic assessment of the labour conditions in magnesium sulphate processing, along with the experimental data on the toxicity of this chemical compound at different ways of its penetration into human body, and describes the damaging mechanisms of its action. The toxicity parameters were related to the 4th class of hazardousness (GOST 12.1.007-76). The acute inhalational action threshold was determined at 112.7 mg/m3. The chemical substance did not exhibit any irritating action on the skin and mucosae, but was capable of penetrating through the undamaged skin and cause some functional disorders. The chronic inhalational action threshold was assessed at 10.2 mg/m3. Magnesium sulphate did not display any specific cardiotoxic or gonadotrophic action. MAC in the air in working zone areas was established at 2 mg/m3. Lesions of the liver were the major factor in the pathogenesis of intoxications. PMID- 1427320 TI - [Skin pathology from exposure to the lubricating coolant fluid MR-7]. AB - The article narrates on pathologic developments in the skin caused by the lubricating cooling liquid MP-7. 63 workers, including machine operators and adjusters, were medically examined, as a result of which it was established that the MP-7 liquid manifested marked irritating properties and less expressed allergenic characteristics. Oil-induced folliculitis, allergic dermatitis and eczema cases constituted 85.4 +/- 4.6% rate, which confirmed the occupational origin of the lesions. Ample supply of hygienic clothes, other hygienic procedures, weekly change of overalls did not fully eliminate contact with the MP 7 liquid. PMID- 1427321 TI - [The epidemiology, diagnosis and prevention of dermatoses in workers manufacturing alumina from different aluminum ores]. AB - Studies of dermatological morbidity in the workers of alumina enterprises showed a lowered incidence of skin lesions caused by common chemical harmfulness and increased incidence of allergic occupational dermatoses. Different types of such dermatoses are related to the ore used. The total level dermatologic morbidity mainly depends on the technology stage of the process but not on the type of raw material. Dermatologic screenings have shown that skin mycoses were the most incident among the dermatoses, whereas analysis of sick-leave records indicates the highest incidence of pyoderma; this necessitates adequate preventive measures. PMID- 1427322 TI - [The Hygiene-1 portable device for studying physical environmental factors]. PMID- 1427323 TI - [The centenary of the founding of the Moscow Hygiene Society]. PMID- 1427324 TI - [The clinical characteristics of the early stages of occupational fluorosis under the combined and joint action of production factors]. AB - Over 1000 workers of hydrofluoric and cryolite enterprises and electrolysis shops of aluminium enterprises were examined. Subjects exposed to soluble hydrofluorides presented in the early stage of chronic intoxication with a variety of syndromes, that was characteristic of intoxication with poisons of general toxic action with involvement of hepatobiliary, digestive, circulatory and autonomic nervous systems. Combined exposure to fluoric compounds, heating microclimate and electromagnetic fields results in a graver involvement of the circulatory and autonomic nervous systems. Clinical and experimental data show, that osteoarthrosis deformans of the major joints (primarily elbow joint) must be regarded as one of the symptoms of fluorosis, when other intoxication signs are present. PMID- 1427325 TI - [The membranogenous action of occupational hazards from the manufacture of black copper on older individuals]. AB - Many-year investigations of health status, aging process and occupational diseases in rough copper production workers, including elderly individuals, revealed the occupational factors (sulphur dioxide, industrial dust, etc.) harmful for membranes. Lowered share of phospholipids containing polyunsaturated fatty acids, that changes the physical and chemical properties of membranes and cellular receptors and enzymes, was found harmful for membranes. The most severe changes were seen in the workers exposed to sulphur dioxide. PMID- 1427326 TI - [The fitness for shift work of operators working according to schedules with a rapid shift rotation]. AB - Integral parameter of professional capacity for work in day and night shifts were studied in 52 operators of heat electric power stations and compared with the results of sociopsychologic questioning. 19% of the operators having higher work capacity in the night shift than in the day one (according to integral parameter) were characterized by lower anxiety, better mood and sleep, and lesser fatigue during the night shift than 19% of examinees, whose night working capacity was lower in comparison with the day shift. The rest 62% of the operators showed a stable level of capacity for work during day and night shifts, their position according to the sociopsychologic parameters is intermediate. PMID- 1427327 TI - [The dependence of the degree of visual fatigue on the shift duration in work with video terminals and an assessment of the efficacy of preventive measures]. AB - Dynamic studies of visual capacity for work in individuals working with displays revealed decreased accommodation volume after the long concentration on the display. The total time of work with the display of more than 2h a day involved a decrease of the accommodation volume by 0.42-0.49 diopters and transitory myopia of 0.15-0.21 diopters, as well as increased self-appraisal of fatigue. The system of prophylactic measures including rest breaks, special exercises, massage was worked out and put into practice. Repeated study has proved the effectiveness of suggested measures. PMID- 1427328 TI - [The pathomorphological changes in the internal organs in experimental chronic red phosphorus poisoning]. AB - Experiments on 76 rats of both sexes exposed to red phosphorus revealed the morphologic changes in the body. Chronic red phosphorus poisoning (15 days, 1, 2, 3, 4 months) induces dystrophic changes and hyperemia in the examined viscera and brain. The first pathomorphologic changes appeared in the liver, stomach, small intestine, and as the intoxication period was prolonged they appeared in other internal organs and brain. PMID- 1427329 TI - [The cytotoxic action of metal stearates and its correlation with the toxicity for animals]. AB - Toxic effects of lead, cadmium, barium, silver, zinc and calcium stearates on the Rh-type cells culture have been revealed. The expressiveness of the cytotoxic action correlated with the toxicity degree for laboratory animals. The strongest (r = 0,98; p less than 0,01) was the correlation between cytotoxicity parameter (the minimal cytoclastic concentration) and the inhalation toxicity parameter in animals (lim(ac)). The results permitted deriving formulae for predicting some toxicity parameters (intraperitoneal LD50, lim(ac)), hygienic regulations (MAC), and showed that the prediction based on cytotoxicity data is more reliable, than that based on toxicometric parameters in short-term experiments used for such purpose. PMID- 1427330 TI - [Experimental data on the hygienic regulation of dimethyl phosphite in the air of a work area]. AB - Dimethylphosphite, being a semiproduct of chlorophosphonium synthesis, is a moderately toxic substance according to the criterion of acute toxicity. It is characterized by marked cumulative properties, absorption from skin and local irritative action. Acute and chronic poisoning induces disorders of the nervous system. MAC in the air is 0.5 mg/m3 as established by Ministry of Health. PMID- 1427331 TI - [The effect of the Earth's weakened magnetic field on the peripheral blood indices of experimental animals]. PMID- 1427332 TI - [A method for performing single-factor dispersion analysis with the transformation of the initial values into relative ones]. AB - Initial data can be transformed into relative to check conclusion about the influence of studied factor on resulting variable. Examples of dispersion analysis on orthogonal and nonorthogonal complexes are given. PMID- 1427333 TI - [The function of mono-oxygenase system in exposure to tricresol (experimental research)]. AB - Studies of monoxygenase system in rat liver exposed to tricresol showed, that the microsomal enzymes status depends on the route of tricresol administration and on the exposure intensity. Monoxygenase system status compared with the serum enzymes activity characterizing the function of the liver showed that changes in microsomal system are more marked, appear earlier and after lower levels of exposure. Changes of cytochrome P-450 enzyme system are the main principle of tricresol harmful action. PMID- 1427334 TI - [The late sequelae of body exposure to phosphorus, fluorine and their derivatives (a review of the literature)]. AB - Presents data on mutagenic, gonadotoxic, embryotoxic and teratogenic activities of phosphorus, fluorine and their derivatives. The investigations have revealed the mechanisms of these chemical substances toxic action on the genetic apparatus, reproductive organs, progeny. The problem is interesting and needs further investigations. PMID- 1427335 TI - [The hygienic bases of laser safety]. AB - Exploitation of laser devices exposes the workers to reflected low-intensity radiation and concomitant physical and chemical factors. Clinical and experimental studies revealed the structural and functional disorders in the organs and body systems exposed to long and constant action of the stated factors, which let the changes be considered as a criterion of the harmful action and serve to base the maximal allowable conditions and assure the safe work conditions when handling laser devices. Harmful and dangerous factors produced by laser device and used materials necessitate the creation of laser equipment of different types and purposes, that will be safe for the personnel handling it. PMID- 1427336 TI - [The correction of hemodynamic disorders with low-intensity infrared laser radiation in agricultural machinery operators with borderline arterial hypertension]. AB - Data on the influence of low-intensity infrared laser on the central and peripheral hemodynamics in 76 agricultural machine operators facing transitory arterial hypertension are presented. Analysis revealed that low-intensity laser is more effective at the early stages of cardiovascular diseases. Low-intensity infrared laser exposure of reflexogenic zones can be effectively used to correct hemodynamic disorders in subjects facing transitory arterial hypertension. PMID- 1427337 TI - [The setting of hygienic standards for harmful substances in the air of a work area 1986-1990]. PMID- 1427338 TI - [The immunological features and morphological characteristics of experimental ulcer formation in sensitization to chromium]. PMID- 1427339 TI - [Industrial hygiene in the modern manufacture of synthetic detergents]. AB - Work conditions in the synthetic detergents production according to the new technology created by Sumitomo (Japan) were evaluated from hygienic point of view. The main unfavourable factor is the contamination of air by initial products (aerosols of sodium tripoli phosphate, carboxy methylcellulose, optic bleacher, enzymes et al.) and dust of the final product. Sulphur oxides appear in the air of the sulphating unit. Levels of noise and vibration are surpassed. At the same time the studied technology is more profitable than the current ones. Parameters of the cardiovascular, central nervous and neuromuscular systems do not indicate the physical and neuropsychic fatigue. PMID- 1427340 TI - [Industrial hygiene in the use of the herbicide Raiser in cotton growing]. PMID- 1427341 TI - [The mechanisms of the formation of pneumoconiosis under high-altitude conditions]. AB - Lipid peroxidation parameters, such as malonic dialdehyde and antioxidant defense (superoxide dismutase and catalase activities) were studied in healthy individuals, miners of different occupations, working at mines of different altitudes. The studies showed that increased lipid peroxidation and decreased antioxidant defense are connected with the altitude of work and exposure to the quartz-containing dust combined with hypobaric hypoxia. Malonic dialdehyde, the final toxic product of peroxidation, is accumulated as a result of it. Increased membranous lipid peroxidation results in death and lysis of cells. It becomes the principal pathogenetic component of pneumoconiosis formation and clarifies the mechanism of its early development, comparatively fast progressing, frequency of nodular forms in miners from the high and middle altitudes. That testifies the ability of hypobaric hypoxia to produce silicosis. PMID- 1427342 TI - [The role of the sweat glands in excreting antimony from the body in people living in the biogeochemical provinces of the Fergana Valley]. AB - The features of antimony excretion by sweat glands were studied in normal subjects and patients with chronic bronchitis, chronic gastritis, chronic nephritis and calculous pyelonephritis, visceral leishmaniasis, living in some biogeochemical provinces of Fergana Valley. A micromethod based on the coloured reaction of the element with brilliant green was worked out to detect antimony in sweat. Sweat antimony elimination was proved to play a significant role in health and disease. The workers engaged in antimony production, the inhabitants of antimony biogeochemical regions should have their sweat excretion tested to score the Sb level. It is recommended as an additional test for screening and controlling the effects of visceral leishmaniasis chemotherapy by solusurmine in patients with kidney disorders. PMID- 1427343 TI - [The immune reactivity characteristics of persons engaged in the manufacture of protein-vitamin concentrates]. AB - Immunologic studies in 130 protein-vitamin concentrate production workers of Angarsk showed the characteristic changes in clinically healthy individuals, suffering from allergic conditions. The changes are: increased levels of T lymphocytes, T killers, T helpers, B lymphocytes, decreased levels of T suppressors and IgA. Immunologic reactivity predisposing to allergic conditions and chronic course of inflammations was found to appear in the workers engaged in protein-vitamin concentrate production. PMID- 1427344 TI - [Dosimetry in setting practical hygienic standards for radio-wave irradiation]. AB - In dosimetric approach to the hygienic norm setting of radio waves adequate metrological basis is required. Joint investigations, carried by physicists and hygienists helped solve the new medical and technical problems, connected with the creation of individual dosimeters and indicators, monitor the hygienic norms of superhigh frequency electromagnetic waves. The devices are small, light, with autonomic power supply and digital indication of current exposure dose. The devices are supposed to give signals (light, sound) if the individual hygienic levels of superhigh frequency electromagnetic waves are surpassed. PMID- 1427345 TI - [The characteristics of the reactions of excitable tissue to combined exposure to microwaves and low-intensity ultrasound]. AB - Isolated pacemaker of the frog's heart served as a sensitive model to study the combined action of the low intensity electromagnetic and mechanic factors. Critical energy levels of factors, their relative efficiency in direct action on the cell were estimated. Additive effects of microwaves and ultrasound were examined. The data can be valuable for the further investigations concerning the effects of different nonionizing rays. PMID- 1427346 TI - [Pathology of the joints of the hand and periarticular tissues in exposure to local vibration and functional overload of the hands]. AB - The hand joint is a multi-joint formation, including the wrist, carpal, intercarpal, carpometacarpal, intermetacarpal, distal radioulnar joints. Features of hand joint and periarticular tissue disease were studied in 536 workers exposed to local vibration and functional overstrain. The most prevalent diseases are arthroses with deformation of the wrist, radiocarpal, carpometacarpal joints, often with involvement of the triangular fibrous disk and carpals, periarthroses of the hand joint with compression neuropathy of the median and ulnar nerves. PMID- 1427347 TI - [The clinical manifestations of chronic exposure to a heating microclimate in metal and forge workers]. AB - Comprehensive examination of 177 workers and screening of more than 2000 workers exposed to heating microclimate revealed the possibility of chronic overheating in some workers and provided the description of its clinical manifestations. Vasoneurosis, myocardiodystrophia and metabolic disorders are the keys to developing of the disease characterized by a rotative course. PMID- 1427348 TI - [Changes in the serum enzymo- and proteinograms of workers in enzyme production suffering from skin diseases (the validation of the diagnosis and of the therapeutic-preventive measures)]. AB - Clinical and epidemiologic examinations of 260 workers engaged in enzyme production revealed the structure of skin disease incidence: mycoses--31%, atopic dermatitis--19%, contact dermatitis--9%, allergic, dermatitis--5%. The majority of these skin diseases were associated with hyperphosphatemia and monoaminoxidase (MAO) depression. Changes of alkaline phosphatase and MAO activities, serum albumins and gamma-globulins may be considered as sensitive markers of disease. PMID- 1427349 TI - [The biological action on the body of animals of small concentrations of the dust from combined feeds]. PMID- 1427350 TI - [The results of clinico-hygienic research in the region of the Mozyr industrial center following the accident at the Chernobyl Atomic Electric Power Station]. AB - The dose of radioactive irradiation received by the workers of the Mozyr industrial area after the Chernobyl power plant accident cannot result in specific lesions, but a nonspecific effects of low radiation doses, chemical substances of low intensity and other occupational factors are possible. A possible radiation origin of the astheno-depressive and astheno-somatic disorders developing by nonspecific stress mechanisms is to be investigated. PMID- 1427351 TI - [Cytochemical research on the peripheral blood erythrocytes and neutrophils of coal miners]. AB - A total of 140 miners, divided into 4 groups were studied. The first group consisted of 25 practically healthy people, newly employed, examined at a health center of the mine, the second of 21 patients with anthracosilicosis, the third of 36 with anthracosilicosis confirmed by X-ray, the fourth included 58 facing the first stage of anthracosilicosis. Erythrocyte histidine and catecholamine levels, myeloperoxidase and beta-glucuronidase activities, data of lysosomal cation (LC) and NBT tests in neutrophils were under study. The miners of groups 2, 3, 4 showed the increased beta-glucuronidase activity (by 47-73%) and NBT test values (37-96%), lowered levels of catecholamines (57-67%), histidine (48-60%), results of LC-test (29-32%) and myeloperoxidase activity (21-31%) in comparison with normal subjects. The findings will help diagnose the latent forms of anthracosilicosis comparatively early, when the structural changes cannot be detected by X-ray. PMID- 1427352 TI - [R proteins as an integral index of the action on the body of industrial allergens in an experiment on white rats]. AB - P proteins were just obtained from white rats and a method to testify them with the help of highly stable anti-P serum was worked out. Normal titres of P proteins are 1:1600 and 1:3200. Different models of sensitisation to the industrial allergens (delivered intracutaneously, by inhalation, into trachea in various doses and concentrations) were used in trials of the method. P protein level appeared to correlate with the sensitisation degree estimated by specific allergy tests. The highest P protein titer is due to the toxic allergic conditions (up to 1:102400), the minimal to sensitization of threshold (up to 1:12800) level. Provocative inhalation test in sensitized rats induced an increase of P protein titer as delayed hypersensitivity was forming. PMID- 1427353 TI - [The establishment of the MPEL for carboxylic acid derivatives in the air of a work area by using mathematical models]. AB - Reports of MACs for carboxylic acid derivatives as sodium methoxyacetate (SMOA), methyl chlorpropionate (MCP) and acetoacetic ether (AAE). SMOA shows low toxicity, no cumulation and specific action MCP demonstrates moderate toxicity, low cumulation no specific action in concentrations close to Limac. AAE presents toxicity low in oral usage and moderate when inhaled, low cumulation, no irritation and sensitization. Tentative safe level of injury and MAC estimated for the aforesaid substances together with toxicity parameters compared with the substances studied before allowed the authors to set the MAC of SMOA--10, MCP--2, AAE--10 mg/m3. PMID- 1427354 TI - [The toxicokinetics of low-solubility substances (exemplified by 2 boron compounds)]. AB - Multichamber toxicokinetic model studies of the resorption, distribution and excretion properties of poorly soluble substances in subchronic action of suspensions administered intragastrically can be the first step in prognosing the toxicokinetic properties of the inhaled aerosols of the substances mostly discharged from the respiratory into the gastrointestinal tract (GIT). The generally accepted quantitative characteristics of the particles' deposition and translocation into GIT can provide a further application of the model for a mathematical description of a prolonged inhalational exposure to some substances. This technique was tested with the boron compounds characterized by low solubility and revealed a good correlation between the prognosed and actual deposits of the substance in the organ and excretions. At the same time, detected were some qualitative and quantitative differences in the boron toxicokinetics influenced by magnesium deboride and hexaborate, which were explained by differences in their solubility. PMID- 1427355 TI - [Improved medical care for miners with ischemic heart disease]. AB - The article is devoted to coronary disease in miners of deep Donbass mines. Data of its prevalence, chemical and functional features are given. Rapid progress of the disease was found to correlate with unfavourable factors of occupational environment. Mechanisms of dangerous heart rythm disorders formation during the work are shown. The main points of the programme improving the health care of miners suffering from coronary heart disease are described. PMID- 1427356 TI - [The measurement of the characteristics of x-ray radiation generated by video display terminals by using thermoluminescent detectors]. AB - Exposure doses of X-rays generated by video displays were measured by means of highly sensitive TLD-500K type detector based on thermoluminophore Al2O3 and DTG 4 type detector based on thermoluminophore LiF. Individual human doses and doses accumulated on the display's surface can be measured. Trials showed efficiency of the method to evaluate the efficacy of protective screens for reducing the irradiation exposure. PMID- 1427357 TI - [Methodological approaches to the analysis of morbidity with temporary loss of work capacity]. AB - The morbidity with temporary disablement (MTD) was studied with the help of Pearson's [correction of Pirson's] criterion in 689 empiric rows. The effect of work conditions on such morbidity was scored by dispersion analysis, demanding to take into account not only intergroup parameters connected with work conditions, but also intragroup ones, depending on casual circumstances, that is why the results should be regarded as preliminary data. The estimated effect of work conditions on the MTD shows unjustified high results for the year, because intragroup parameters were levelled. PMID- 1427358 TI - Psychoautonomic approaches to migraine. PMID- 1427359 TI - Pain threshold in humans. A study with the pressure algometer. AB - Pain perception threshold (PPT) in the head was assessed with a pressure algometer in 40 control individuals (24 females and 16 males). Threshold was assessed at 11 symmetrical points on each side. The average threshold for each side was calculated, and differences between two sides were evaluated with an asymmetry index. Subjects were studied in relation to age and sex, and any difference in the symmetrical perception of pain on the head was registered. The deltoid muscle was chosen as a reference point, since it is rarely a site of trigger points. The reproducibility of the method was satisfactory. A significantly positive correlation was found between PPT value of the head and the deltoid muscle. There was no tendency to rise or fall in PPT during the same "session", which consisted of 3 separate complete measurements. The mean of mean values showed that there was little asymmetry as for the thresholds pertaining to the head in the total material. Age and sex apparently played little role as for the outcome of the test. The assessment of PPT in the head might be a useful tool in the study of lateralization of pain in unilateral headache syndromes. PMID- 1427360 TI - Laterality of pain and other migraine criteria in common migraine. A comparison with cervicogenic headache. AB - Patients diagnosed as suffering from common migraine according to the "Ad hoc committee" criteria of 1962 have been studied as for type of unilaterality of headache. Patients, with trauma to the face, head, and neck were excluded, together with patients with the faintest suspicion of aura and those with chronification of the headache. Common migraine criteria, as stipulated by the IHS and Vahlquist, were counted in every patient (n = 32), except the laterality which was a free variable (a total of 8 variables remaining). For comparison, as far as the number of migraine criteria is concerned, a group of cervicogenic headache patients was also studied (n = 30). Unilaterality with side shift of pain was present in 75% in the common migraine group; in 34% of the patients, a combined pattern, i.e. bilateral headache + unilaterality with sideshift was present. Common migraine, therefore, just as classic migraine, seems to be a headache characterized by unilaterality with side alternation of pain. Common migraine criteria were present to a high degree in common migraine patients selected in this way, i.e. ca. 6.8 of a maximum of 7. In cervicogenic headache, the corresponding figure was ca. 3.8 (of a maximum of 7). These figures are statistically significantly different (p < 1.3 10(-11), Mann-Whitney test). Still, the level of criteria is relatively high in cervicogenic headache, and 6 of 30 patients would fulfil the IHS common migraine criteria. PMID- 1427361 TI - Apomorphine test in de novo Parkinson's disease. AB - We administered apomorphine, a powerful dopaminergic agonist, subcutaneously to 25 untreated patients with parkinsonian features and evaluated motor response with the aim of discriminating idiopathic Parkinson's disease (IPD) from multiple system atrophy and progressive supranuclear palsy. The response to apomorphine was strongly predictive of responsiveness to subsequent levodopa follow-up and of the final diagnosis, made on the basis of both clinical and instrumental evaluation. Our data confirm that the apomorphine test is helpful in the differential diagnosis of IPD. PMID- 1427362 TI - Length of social deprivation differently affects free-choice morphine consumption in C57BL/6J mice. AB - The effects of social deprivation on morphine consumption in C57BL/6J mice were investigated. Social or isolated animals (length of isolation: 7, 12, 17 days) were submitted to a free-choice between water and morphine hydrochloride solution (0.5 mg/ml). Isolation affects morphine consumption, with solitary housed mice drinking more morphine solution than socially housed animals. Moreover the amount of morphine intake depends on the duration of the isolation period to which mice are subjected. The importance of environmental factors on opiate consumption may be considered in terms of the possible implications of drug addiction in humans. PMID- 1427363 TI - Chemotherapy for gastric cancer. PMID- 1427364 TI - Length of Barrett's oesophagus: an important factor in the development of dysplasia and adenocarcinoma. AB - In a 15 year prospective study of endoscopic surveillance of columnar lined oesophagus, 102 patients with a mean follow up of 54 (12.5) months and total follow up of 462 years have been evaluated. Of all the sets of biopsies taken, 59 in 21 patients were found to exhibit dysplasia or carcinoma. Four male patients had carcinoma of the oesophagus, indicating a 30 times increased risk of development of adenocarcinoma in columnar lined oesophagus. The length of columnar lined oesophagus in subjects with dysplasia was significantly longer as compared with the whole group (p = 0.01) and when compared with the patients without dysplasia (p = 0.005). None of the patients with dysplasia had a columnar lined oesophagus of less than 8 cm. Length of columnar lined oesophagus therefore seems to be a significant risk factor in the development of dysplasia and subsequent carcinoma and intensive follow up of patients with columnar lined oesophagus greater than 8 cm in length is recommended. PMID- 1427365 TI - Comparison of endoscopic injection therapy versus the heater probe in major peptic ulcer haemorrhage. AB - One hundred and twenty patients presenting with major peptic ulcer haemorrhage were randomised in a clinical trial comparing endoscopic injection and heater probe therapy. The two groups were well matched with regards to age, admission haemoglobin concentration, the presence of shock, non-steroidal anti-inflammatory drug usage and endoscopic findings. Permanent haemostasis was achieved in 87% of the injection group and 85% of the heater probe group. Hospital mortality, transfusion requirement and duration of admission were similar in both groups. Endoscopic injection and the heater probe represent equally effective therapy for peptic ulcer bleeding. PMID- 1427366 TI - Mucosal peptic activity during Helicobacter pylori infection in pediatric patients. AB - Intramucosal peptic activity may participate in the genesis of acute and chronic superficial gastritis. The proteolytic activity of homogenates of gastric mucosa (antrum and body) and duodenum were measured at pH 2.0 (total peptic activity) after exposure to pH 8.0 (pepsinogen) and the activated pepsinogen (pepsin) was calculated in pediatric patients investigated for the presence of Helicobacter pylori (H pylori), 122 antral, 77 stomach body, and 74 duodenal biopsies were examined in 43 H pylori positive patients, 51 controls, and 28 H pylori negative gastritis patients. Activated pepsinogen was significantly reduced in the stomach of H pylori positive patients only. Pepsinogen values were similar in all the anatomical areas tested in all patients. In 13 H pylori positive patients reinvestigated three months after antibiotic therapy, antral mucosal activated pepsinogen activity increased significantly (mean pretreatment 1.56 (1.0) U/mg protein versus mean post-treatment 2.72 (1.7) U/mg protein) and reached values comparable with controls. The decreased activated pepsinogen activity in association with normal pepsinogen content observed in the antrum of H pylori positive gastritis patients indicate local pepsin inactivation or alternately enhanced removal into the gastric lumen or backflow into the circulation. PMID- 1427367 TI - Effect of acute cigarette smoking on gastric secretion. AB - The effects of smoking one cigarette on a plateau of submaximal gastric secretion induced by histamine acid phosphate (16 nmol kg-1 h-1 (0.005 mg kg-1 h-1)) were measured in eight normal volunteers and in eight duodenal ulcer subjects. The rate of secretion in both groups fell by 25% without any statistically significant change in pyloric loss or duodenogastric reflux. It is concluded that smoking reduces gastric secretion. The possibility that relative antral hypoacidity induced by regular smoking produces an increase in parietal cell mass via a feedback mechanism mediated by gastrin is discussed: such a mechanism would explain the previously reported positive correlation between maximal gastric secretion of acid and the total dose of cigarettes. PMID- 1427368 TI - Effect of cholera toxin on the human jejunum. AB - In order to develop a model for secretory diarrhoea and to confirm the in vitro effects of cholera toxin in man in vivo the effect of intrajejunally administered cholera toxin was investigated in healthy volunteers. An intestinal perfusion technique with an occluding balloon proximal to the infusion site was used. The jejunum was perfused under steady state conditions with a plasma like electrolyte solution containing polyethylene glycol as a non-absorbable volume marker. After two control periods of one hour each, during which water was absorbed at a rate of 104 (14) (mean (SEM), n = 15) and 94 (15) ml/30 cm/h, respectively, three different doses of cholera toxin (6.25 micrograms, 12.5 micrograms, 25 micrograms) were administered by bolus into the lumen of the jejunum. Cholera toxin reduced absorption of water and electrolytes progressively over four hours and induced secretion in a dose dependent fashion. In the fourth hour net secretion amounted to 22 (23), 36 (24), and 88 (40) ml/30 cm/h (each n = five) with doses of 6.25, 12.5, and 25 micrograms cholera toxin, respectively. The movement of sodium, chloride, and bicarbonate paralleled water movement. Our results suggest that cholera toxin may serve as a secretory model in the human jejunum which might allow testing of new antisecretory agents. PMID- 1427369 TI - Cow's milk provocation induces an immune response to unrelated dietary antigens. AB - The activation of immune mechanisms was evaluated by the solid phase enzyme linked immunoassay of immunoglobulin and specific antibody secreting cells in 27 patients (aged from nine to 69 months), subjected to a diagnostic cow's milk challenge or a rechallenge. A significant rise in the total number of immunoglobulin secreting cells was associated with clinically positive (n = 17), but not a negative (n = 10) cow's milk challenge in all immunoglobulin isotypes. The number of specific antibody secreting cells against beta lactoglobulin, mean (95% confidence interval), increased from 4.8 (1.4, 15.8) to 16.9 (5.5, 52.7) specific antibody secreting cells/10(6) cells, p = 0.02, and against casein from 2.2 (0.8, 6.1) to 7.5 (2.5, 22.5) specific antibody secreting cells/10(6) cells, p = 0.01, in patients positive to challenge in the IgM class only, indicating defective immune elimination of milk antigens. In addition to the specific immune response to cow's milk antigens, an increase in IgM specific antibody secreting cells against an unrelated dietary antigen, gliadin, from 8.2 (2.1, 31.1) to 31.0 (14.2, 67.6) specific antibody secreting cells/10(6) cells, p = 0.01, was observed. These results indicate that cow's milk challenge, in patients who have cow's milk allergy, induces a strong non-antigen specific immune response that includes a response against unrelated antigens concomitantly present in the intestinal lumen. Activation of such immune mechanisms may hence reflect increased antigenic load caused by the immune mediated lesion in the gut mucosa. PMID- 1427370 TI - Activated eosinophils in adult coeliac disease: evidence for a local release of major basic protein. AB - The eosinophil population is increased in the jejunal mucosa of patients with coeliac disease. Eosinophils may participate in the mucosal damage by releasing their granule components that have cytotoxic properties such as eosinophil cationic protein (ECP) and major basic protein (MBP). This study aimed to assess the presence of ECP and MBP in the jejunal mucosa of 10 adult patients with active coeliac disease who presented with villous flattening. Endoscopic jejunal biopsy specimens were obtained from macroscopically flattened jejunal mucosa and were processed for ultrastructural study and immunogold labelling using anti-MBP, anti-ECP, and anti-IgA antibodies. Numerous eosinophils were found in the upper part of the lamina propria and showed two types of morphological change: some were lytic and others exhibited ultrastructural signs of activation, containing altered granules with fading of the central core. IgA plasma cells were intermingled with eosinophils and had dense deposits on the external side of their cytoplasmic membrane. MBP was detected in central cores of granules but also diffusely in their matrix and in tight association with dense extracellular deposits. Conversely, ECP was detected only in the matrix of eosinophil granules. This study showed that numerous eosinophils are in an activated state in the mucosa of patients with active coeliac disease and release cytotoxic proteins such as MBP, which could contribute to the mucosal damage. The observation that eosinophils and IgA plasmocytes were closely associated in the mucosa supports a role for IgA in eosinophil recruitment and activation in coeliac disease. PMID- 1427371 TI - Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy. AB - Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p < 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p < 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p < 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system. PMID- 1427372 TI - Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy. AB - This study assessed the effect of metronidazole on the gastroduodenal mucosa, intestinal permeability, blood loss, and inflammation in patients on non steroidal anti-inflammatory drugs (NSAIDs). Thirteen patients were studied before and after 2-12 weeks' treatment with metronidazole 800 mg/day, while maintaining an unchanged NSAID intake. Intestinal inflammation, as assessed by the faecal excretion of indium-111 labelled neutrophils, and blood loss, assessed with chromium-51 labelled red cells, were significantly reduced after treatment (mean (SD) 111In excretion 4.7 (4.7)% v 1.5 (1.3)% (N < 1.0%), p < 0.001, 51Cr red cells loss 2.6 (1.6) ml/day v 0.9 (0.5) ml/day (N < 1.0 ml/day), p < 0.01). Intestinal permeability assessed as the 5 hour urinary excretion ratio of 51CrEDTA/L-rhamnose did not change significantly (0.133 (0.046) v 0.154 (0.064), p > 0.1) and there were no significant changes in the endoscopic or microscopic appearances of the gastroduodenal mucosa. These results suggest that the neutrophil is the main damaging effector cell in NSAID induced enteropathy. The main neutrophil chemo-attractant in this enteropathy may be a metronidazole sensitive microbe. PMID- 1427373 TI - Polymerase chain reaction detection of Mycobacterium paratuberculosis and Mycobacterium avium subsp silvaticum in long term cultures from Crohn's disease and control tissues. AB - Thirty one cultures were established in MG3 medium from the intestinal tissues of 29 patients, including 18 with Crohn's disease, five with ulcerative colitis, and six non-inflammatory bowel disease controls. All cultures grew either acid fast bacilli or uncharacterized spheroplasts. Pellets from these cultures were coded and assayed blind for M paratuberculosis and M avium subsp silvaticum using IS900 and IS902-PCR (polymerase chain reaction) assays, respectively. IS900 and IS902 are multicopy DNA insertion elements specific for these two organisms. Six Crohn's disease cultures and a single non-inflammatory bowel disease control were positive for M paratuberculosis. A further six cultures were positive for M avium subsp silvaticum, of which two each were from Crohn's disease, ulcerative colitis, and non-inflammatory bowel disease controls. The intensity of the IS900 PCR signals indicated very low numbers of M paratuberculosis organisms and bore no relation to visible spheroplastic or bacillary mycobacterial growth. The results suggest that M paratuberculosis isolated from man exists in a form which hardly replicates if at all when cultured in MG3 medium in vitro, and are consistent with the involvement of this known animal enteric pathogen in a proportion of chronic enteritis in man. PMID- 1427374 TI - Detection of mRNAs for macrophage products in inflammatory bowel disease by in situ hybridisation. AB - In situ hybridisation has been used to detect mRNAs to the macrophage secretory products, lysozyme, interleukin 1 beta and tumour necrosis factor-alpha. Sections of paraformaldehyde fixed, frozen colonoscopic biopsies from patients with ulcerative colitis, Crohn's disease or normal controls were hybridised with specific radiolabelled probes and the signal detected by autoradiography. Lysozyme mRNA expression was more common in ulcerative colitis (22/27) and Crohn's disease (eight of eight) compared with controls (17/27). Positive cells were found mainly in the subepithelial region in normal colon, while in inflammatory bowel disease they also appeared in the deeper lamina propria. Immunocytochemistry in parallel sections showed that lysozyme mRNA was expressed only in macrophages or in metaplastic Paneth cells in longstanding inflammatory bowel disease. Tissue neutrophils did not express the lysozyme mRNA, though they have large stores of the protein. Tumour necrosis factor mRNA was detected in four of nine controls compared with 11/15 inflammatory bowel disease patients. For interleukin 1 beta, three of eight controls were positive compared with 10/13 with ulcerative colitis. The tumour necrosis factor signal was located mainly in the deeper lamina propria whereas the interleukin 1 beta was seen in subepithelial macrophages. These results confirm increased macrophage activation in inflammatory bowel disease and suggest functional heterogeneity within the intestinal macrophage population. PMID- 1427375 TI - Raised concentrations of platelet activating factor in colonic mucosa of Crohn's disease patients. AB - Platelet activating factor (PAF-ACETHER or PAF) and precursors of platelet activating factor were investigated in 26 patients with acute Crohn's disease and in 10 healthy controls. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine, were determined in colonic mucosal biopsies in patients with acute Crohn's disease, during prednisolone therapy, and in remission. Biopsy specimens were submitted to histopathology examination and to phospholipid extraction. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine were found in patients with acute Crohn's disease and in remission as well as in controls. Whatever the site of the biopsy, the level of platelet activating factor in colonic mucosa was higher (p < 0.01) in Crohn's disease than in controls. There was no correlation between the level of colonic PAF-ACETHER and age, sex, Crohn's disease activity index, and biological parameters in sera. Although concentrations of colonic platelet activating factor content were higher (p < 0.01) when colonic mucosa displayed cell infiltration, they were neither related to the severity nor the type of inflammatory cells. Platelet activating factor decreases with prednisolone therapy and might return to normal concentrations in quiescent patients. Lyso platelet activating factor and alkyl acyl glycerophosphocholine were not significantly higher in Crohn's disease than in controls. These data suggest that platelet activating factor may be involved in the pathogenesis of Crohn's disease and that it could be used as a marker of the mucosal activity of the disease. PMID- 1427376 TI - Mortality from Crohn's disease in Leicestershire, 1972-1989: an epidemiological community based study. AB - Mortality among 610 people with Crohn's disease identified in a population based study from 1972-89 was assessed. In Europeans the overall mortality was not increased, the standardised mortality ratio (SMR) was 71.8 (95% confidence interval (CI) 49 to 101). The SMR in South Asians was 0, (95% CI 0 to 1590). The SMR varied with the site of disease (chi 2 (4) = 10.5, p < 0.05) and was highest in those with duodenal and jejunal involvement (SMR = 210, 95% CI 44 to 621). Survival curve comparisons showed that colonic disease carried a worse prognosis than terminal ileal disease (chi-2 = 9, p < 0.01) or mixed site disease (chi-2 = 4.7, p < 0.05). Mortality was particularly high during the first six years. It was increased in patients who had undergone more than one resection (SMR = 137, 95% CI 28 to 401) or an ileoanal anastomosis (SMR = 357, 95% CI 9 to 1070), although no difference was significant. Mortality did not change significantly during the study. Such information needs to be made available, not just to patients, their families, and their doctors, but perhaps more importantly, to actuaries, insurers, and those advising employers. PMID- 1427377 TI - Role of dietary sulphate in the regulation of methanogenesis in the human large intestine. AB - Hydrogen produced during colonic fermentation may be excreted, or removed by H2 consuming bacteria such as methanogenic and sulphate reducing bacteria. In vitro, sulphate reducing bacteria compete with methanogenic bacteria for hydrogen when sulphate is present. In this study the hypothesis that sulphate in the diet could alter CH4 production in vivo has been tested. Six methane excreting volunteers were fed a low sulphate diet (1.6 mmol/d) for 34 days with the addition of 15 mmol sodium sulphate from days 11-20. Breath methane was measured and viable counts and metabolic activities of methanogenic bacteria and sulphate reducing bacteria determined in faeces. Whole gut transit time and daily stool weight were also measured. When sulphate was added to the diet, breath methane excretion decreased in three of the subjects while faecal sulphate reduction rates rose from 7.5 (0.5) to 20.3 (4.3) nmol SO4 reduced/h/g faeces. Sulphate reducing bacteria, which were not detected during the control diet, were found and viable counts of methanogenic bacteria fell from 10(7)-10(9)/g faeces to 10(6)/g. Methanogenic counts and breath CH4 recovered after sulphate addition was stopped. No change was found in the other three subjects. Faecal weights and transit times were not different between study periods. It is concluded that methanogenesis is regulated by dietary sulphate if sulphate reducing bacteria are present. Dietary sulphate may allow growth of sulphate reducing bacteria which inhibit the growth of methanogenic bacteria. This may explain the absence of CH4 in the breath of many people in western populations. PMID- 1427378 TI - Faecal unconjugated bile acids in patients with colorectal cancer or polyps. AB - The unconjugated faecal bile acid profiles of 14 patients with colorectal cancer, nine patients with polyps and 10 controls were compared using gas liquid chromatography, controlling for such confounding variables as cholecystectomy, gall stones and hepatic function. Patients with adenomatous polyps had a higher concentration of faecal bile acids (5.23 mumol/g, 2.16-13.67 (median, range) v 1.96, 0.91-6.97; p = 0.016) lithocholic acid (2.41, 0.88-3.22 v 1.07, 0.38-2.03; p = 0.013) and total secondary bile acids (5.23, 2.16-13.4 v 1.96, 0.73-6.63; p = 0.02) compared with control subjects. Patients with colorectal cancer had an increased (p = 0.029) proportion of secondary faecal bile acids (mol%) compared with controls (100, 96.5-100 v 95.19, 81.73-100) and the ratios of the primary bile acids, cholic and chenodeoxycholic acid, to their respective derivatives (secondary bile acids) were significantly lower in cancer patients compared with control and patients with polyps (p = 0.034 to 0.004). This study lends further support to the theory that bile acids may play a role in the development of polyps and colorectal cancer. PMID- 1427379 TI - Effects of alpha-glucosidase inhibitors on mouth to caecum transit time in humans. AB - The alpha-glucosidase inhibitors acarbose and miglitol have been successfully used to control postprandial hyperglycaemia in diabetics. They probably work by slowing carbohydrate digestion and absorption, but their effect on mouth to caecum transit time has not been studied. The effect acarbose (100 mg), miglitol (100 mg), and placebo on mouth to caecum transit time (380 kcal breakfast with 20 g of lactulose) was investigated in 18 normal volunteers using breath hydrogen analysis. Both miglitol and acarbose significantly increased breath hydrogen excretion (F2,34 = 6.31, p = 0.005) and shortened the mouth to caecum transit time (F2,34 = 3.49, p = 0.04) after breakfast compared with placebo. There was a significant negative correlation between breath hydrogen excretion and mouth to caecum transit time suggesting that with shorter transit times significantly more carbohydrates were spilled into the colon. These results indicate that alpha glucosidase inhibitors accelerate mouth to caecum transit time by inducing carbohydrate malabsorption. PMID- 1427380 TI - Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instillation at surgery. AB - The major end products of fermentation, short chain fatty acids (acetate, propionate, butyrate) were measured in portal and peripheral venous blood after the caecal instillation of lactulose at surgery in patients undergoing elective cholecystectomy. Blood samples for short chain fatty acid measurement were taken before and at 15 minute intervals up to 60 minutes after caecal instillation of either 20 ml sterile saline or 6.7 g or 10 g lactulose. Fasting concentrations (n = 28) were (mumol/l, mean (SD)); portal acetate 128.0 (70.8), propionate 34.4 (23.3), butyrate 17.6 (18.4); peripheral acetate 67.0 (23.0), propionate 3.7 (1.2), butyrate traces only. After lactulose there was a rapid rise in portal short chain fatty acids with peak concentrations being reached in 15 to 45 minutes. Mean peak concentrations (mumol/l (SD)) after 10 g lactulose were acetate 240.9 (142.2), propionate 39.0 (17.8) and butyrate 26.9 (17.6). The changes in acetate concentrations seen in portal blood were reflected in peripheral blood acetate measurements. In contrast with portal blood, only small amounts of propionate and traces of butyrate were found in peripheral blood. PMID- 1427381 TI - Selection, management, and early outcome of 113 patients with symptomatic gall stones treated by percutaneous cholecystolithotomy. AB - Between January 1988 and December 1990, 283 patients with symptomatic gall stones were referred for non-operative treatment. After ultrasound scanning including a functional assessment, 220 (78%) patients were found to be suitable for percutaneous cholecystolithotomy. Of these, 113 underwent the procedure including 10 in whom extracorporeal shock-wave lithotripsy or methyl tert-butyl ether therapy had failed. Forty four patients underwent extracorporeal shockwave lithotripsy, methyl tert-butyl ether therapy or rotary lithotripsy, 46 chose laparoscopic cholecystectomy or minicholecystectomy and 27 declined treatment. Percutaneous cholecystolithotomy was successfully performed in 100 patients. Thirty four patients were a high operative risk and 14 presented with an acute complication of gall stone disease. Complications developed in 15 patients, all of whom were managed conservatively and most occurred during development of the technique. Outcome has been assessed clinically and by ultrasound scanning in 92 patients with a median follow up period of 14 months (six to 37 months). Seventy nine per cent were completely cured of their symptoms. Ninety three per cent of gall bladders were shown to be functioning and nine (9.8%) contained stones, although five of these are believed to have developed from residual fragments. Percutaneous cholecystolithotomy is a safe, non-operative treatment for symptomatic gall stones and enabled the patient to fully recover within two to three weeks; it has a definite role in the management of the elderly and high risk patient but its use for the treatment of other groups is likely to remain controversial. PMID- 1427382 TI - Role of interleukin-6 in acute pancreatitis. Comparison with C-reactive protein and phospholipase A. AB - Plasma values of immunoreactive interleukin-6, C-reactive protein and phospholipase A have been determined in serial samples from 24 patients with acute pancreatitis ('mild' pancreatitis nine, 'severe' pancreatitis 15). Median plasma concentrations of interleukin-6, C-reactive protein, and phospholipase A activity were significantly higher in patients with 'severe' illness (p < 0.001) than those with 'mild' illness. A particularly marked increase in interleukin-6 was found in two patients with necrotising pancreatitis and fatal outcome. Significant correlations between plasma concentrations of interleukin-6 and phospholipase A (p = 0.0218) and C-reactive protein and phospholipase A activity (p < 0.0001) were found in patients with 'severe' disease. These findings in a limited number of patients with acute pancreatitis are promising in that raised interleukin-6 correlated with clinical severity and with two other established markers, C-reactive protein, and phospholipase A activity. PMID- 1427383 TI - Familial and idiopathic colonic varices: an unusual cause of lower gastrointestinal haemorrhage. AB - A patient is described presenting with an acute lower gastrointestinal haemorrhage as a result of extensive colonic varices. Further investigation revealed that there were no oesophageal varices or splenomegaly. Liver biopsy showed grade II fatty change only, with no other specific or significant pathological features. Transhepatic portography showed a raised portal pressure (20 mm/Hg) but the portal system was patent throughout. There was an abnormal leash of vessels in the caecum thought to represent a variceal plexus. This patient was diagnosed as having idiopathic colonic varices. This case is discussed together with nine other reports of idiopathic colonic varices from the published literature. Four of these reports describe idiopathic colonic varices in more than one member of the same family. Possible modes of inheritance, aetiology of variceal change, natural history, and prognosis are discussed. PMID- 1427384 TI - Helicobacter pylori and peptic ulcer recurrence. PMID- 1427385 TI - Helicobacter pylori and peptic ulcer recurrence. PMID- 1427386 TI - Estimation of total hepatic blood flow by duplex ultrasound. PMID- 1427387 TI - The new paradigms that will take us into the twenty-first century. PMID- 1427388 TI - Intraperitoneal therapy of malignant ascites associated with carcinoma of ovary and breast using radioiodinated monoclonal antibody 2G3. AB - A phase I/II study of intraperitoneal (ip) radioimmunotherapy was conducted in ovarian or breast cancer patients with symptomatic chemotherapy-resistant ascites using a novel anti-mucin monoclonal antibody (mAb) 2G3 labeled with 131I. Tracer doses of 2 mCi [131I]2G3 were given by ip injection to 11 patients, followed by increasing therapeutic doses up to 150 mCi (cumulative) in 9 patients. There was no serious toxicity. Temporary palliation of ascites was observed in 3 of 4 patients who received doses greater than 50 mCi. Total body elimination half-life of the radiolabeled antibody assessed by gamma scintigraphy ranged from 95 to 250 hr, longer than data previously reported in patients without ascites treated with ip administered radiolabeled antibodies. However, uptake of radiolabel by tumor nodules was small and variable (2 x 10(-4) - 2 x 10(-2) % ID/g), and preferential uptake by tumor compared to normal peritoneum was observed in only 2 of 5 patients in whom biopsies were obtained. These results suggest that the observed palliation of ascites is due to prolonged retention of radiolabeled antibody in the peritoneal cavity even in the absence of specific targeting. PMID- 1427390 TI - Spontaneous internal jugular vein thrombosis associated with leiomyosarcoma of the omentum. AB - A case of spontaneous internal jugular vein thrombosis associated with distant malignancy is presented. This unusual manifestation of a hypercoagulable state was associated with a low-grade epithelioid leiomyosarcoma of the omentum. It was discovered on a gynecologic oncology service in a patient explored for a pelvic abdominal mass. PMID- 1427389 TI - Hip disarticulation for recurrent vulvar cancer in the groin. AB - A patient with squamous cell carcinoma of the vulva treated with a radical vulvectomy and bilateral inguinal and femoral lymphadenectomies utilizing separate groin incisions, subsequently developed a recurrence in the skin bridge between the vulvar and groin excisions. Following groin irradiation with chemosensitization, the tumor progressed to involve the superior public ramus and femoral vessels. A left hip disarticulation and resection of a portion of the superior pubic ramus was performed. The patient has been free of disease for 3 years. The advantages of this procedure over a hemipelvectomy include shorter operative time, reduced blood loss, better fascial closure of the abdomen, and the creation of a stump which is more amendable to prosthetic fitting. PMID- 1427391 TI - False-positive elevation of CA-125 in papillary serous carcinoma of the endometrium treated with postoperative whole abdominal radiation. AB - Two patients with Stage I papillary serous carcinoma of the endometrium treated with postoperative whole abdominal radiation developed elevated CA-125 levels. In neither patient was evidence of recurrent disease identified. Hepatic veno occlusive disease, a known complication of whole abdominal radiation and certain chemotherapy regimens, was confirmed by liver biopsy in both cases. CA-125 levels may not be reflective of disease status in this setting. PMID- 1427392 TI - Radiation sensitivity of endometrial carcinoma in vitro. PMID- 1427393 TI - Prognostic value of CA 125 in advanced cancer. PMID- 1427394 TI - Synchronous radiation and cytotoxic chemotherapy for locally advanced or recurrent squamous cancer of the vulva. AB - Between July 1987 and September 1991 a program of external beam radiation and synchronous, radiopotentiating chemotherapy was employed to treat 25 women with locoregionally advanced or locoregionally recurrent squamous cancer of the vulva. Of 18 previously untreated patients, 1 was Stage II, 10 were Stage III, 6 were Stage IVA, and 1 was Stage IVB. Reasons for patient referral for nonsurgical management included the presence of initially unresectable disease (5 patients), disease extent which would have necessitated partial or total exenteration if treated surgically (9 patients), disease extent predictive of inadequate surgical margins (less than 1 cm gross margin) if treated by less than exenterative surgery (8 patients), and severe comorbid illness precluding surgical management (3 patients). Complete clinical response was obtained in 16 of 18 previously untreated patients (89%) and in 4 of 7 patients with recurrent disease following vulvar surgery (57%). Of 20 patients achieving a complete clinical response, 3 patients have relapsed within the irradiated volume at 11, 38, and 48 months following completion of treatment. Fourteen patients remain alive and continuously cancer free from 2-52 months after completion of treatment (median follow-up 24 months). This experience suggests that initial management with radiation and chemotherapy may offer some patients with locally advanced squamous cancer of the vulva an alternative to exenterative surgery and may hold curative potential for some patients with surgically unresectable or medically inoperable disease. PMID- 1427395 TI - Bulky stage IB cervical carcinoma managed by primary radical hysterectomy followed by tailored radiotherapy. AB - The management of bulky, stage IB cervical carcinoma remains controversial. The present study reports the outcome of 84 women treated by radical hysterectomy, in which the surgical specimen revealed a lesion measured to be 4 cm or greater in size following formalin fixation. Of the 84 women, 42 (50%) received postoperative radiotherapy based on additional surgical findings beyond tumor size suggesting a high risk for pelvic recurrence including lymph node metastasis, parametrial spread, and compromised margins. Despite the bulky nature of these lesions, major operative and early postoperative complication rates were low (6%). Delayed complications including fistulae and bowel obstructions occurred in only 2.4% of patients treated with surgery alone and in 14.2% of women treated with combined therapy. Corrected 5-year survival in this series was 70.4% (75.6% in the surgery only group and 65.0% in the surgery plus radiotherapy group). Recurrence and mortality rates were related to lesion size, with most recurrences and deaths occurring in women with lesions measuring 6 cm or greater. Comparison of these data utilizing primary radical hysterectomy followed by tailored radiotherapy with previously published data on similar groups of high risk patients treated with either radiotherapy alone or with radiotherapy followed by simple hysterectomy suggests comparable survival and morbidity. PMID- 1427396 TI - The effects of cyclosporin A on the lysis of ovarian cancer cells by cisplatin or adriamycin. AB - The major limitation to curative therapy for ovarian cancer is the development of drug resistance. Cyclosporin A (CsA), an immunosuppressive agent that has been used extensively in organ transplantation, also has been shown to decrease the resistance of cancer cells to some chemotherapeutic agents. Since cisplatin (CDDP) is the most common drug used for the treatment of ovarian cancer, we evaluated the potential of CsA to decrease resistance to CDDP in ovarian cancer cells selected for resistance to CDDP (A2780-CDDP). Although CsA significantly increased the sensitivity of A2780-CDDP cells to cytolysis by CDDP it did not increase CDDP sensitivity in the CDDP-sensitive parent cells (A2780), that is, CsA did not decrease basal resistance to CDDP. Both A2780-CDDP and A2780 are sensitive to cytolysis by Adriamycin (ADR). CsA significantly decreased the basal resistance of both cell lines to ADR. Interestingly, the effect of the protein synthesis inhibitors, emetine and cycloheximide, was similar to that of CsA, suggesting that CsA decreased selected resistance to CDDP and decreased basal resistance to ADR by affecting a protein synthesis-dependent resistance mechanism(s). In contrast to CsA and protein synthesis inhibitors, buthionine sulfoximine, an inhibitor of glutathione synthesis, decreased basal resistance of both cell lines to cytolysis by CDDP but not ADR, while verapamil, an inhibitor of P-glycoprotein, had no effect on cytolysis in either cell line. These results suggest that CsA may not decrease resistance to CDDP or ADR-mediated cytolysis by reducing glutathione or by inhibiting P-glycoprotein. PMID- 1427397 TI - A comparison of staging systems for squamous cell carcinoma of the vulva. AB - A review of 172 patients with squamous cell cancer of the vulva treated at the University of Michigan Medical Center from 1975-1989 was performed to compare the 1988 FIGO Staging System to the 1970 FIGO Staging System. The stage distribution according to the 1970 FIGO Staging System was stage I, 65; stage II, 44; stage III, 50; and stage IV, 13. The cumulative 5-year survival under the old system was stage I, 94%; stage II, 91%; stage III, 36%; and stage IV, 26%. The distribution changed under the 1988 FIGO system to stage I, 58; stage II, 36; stage III, 49; stage IVA, 16; and stage IVB, 13. The cumulative survival also changed to stage I, 94%; stage II, 89%; stage III, 71%; stage IVA, 19%; and stage IVB, 8%. The new FIGO stage distribution shifted for the worse due to the influence of positive lymph nodes found at the time of surgery. The survival was then analyzed for death from all causes. This was markedly decreased when compared to the cumulative corrected survival. This relates to the high number of other primary malignancies and the age of the patients. Among these 172 patients, other primary malignancies included squamous cell cancer of the cervix (11), squamous cell cancer of the vagina (2), endometrial cancer (3), squamous cell cancer of the lung (2), colon cancer (3), and others (6). An additional 5 patients died from myocardial infarction within 2 years of diagnosis. The new 1988 FIGO Staging System provides for better discrimination of survival between stages than the 1970 FIGO Staging System. PMID- 1427398 TI - The role of laparoscopic lymphadenectomy in the management of cervical carcinoma. AB - Laparoscopic lymphadenectomy was performed on 18 patients with invasive carcinoma of the cervix prior to definitive radiation therapy and/or radical hysterectomy. Ten patients underwent pelvic and para-aortic lymphadenectomies prior to planned radiotherapy. Two of these patients had grossly positive pelvic nodes, and one had a microscopically positive para-aortic node. Eight patients with early disease were considered candidates for radical hysterectomy and underwent laparoscopic lymphadenectomy. Three of these patients were found to have positive pelvic lymph nodes and the hysterectomy was abandoned. Five patients underwent radical hysterectomies immediately following their laparoscopic procedures. The average number of lymph nodes removed laparoscopically in these patients was 31.4; the average number of additional lymph nodes resected at laparotomy with the radical hysterectomy was 2.8. A single microscopically positive parametrial lymph node was found on permanent section in 1 patient with radical hysterectomy. No significant complications were associated with the laparoscopic lymphadenectomies. Nine of the 13 patients who underwent laparoscopic procedures only were discharged on Postoperative Day 1. The ability to perform pelvic and para-aortic lymphadenectomy allows for complete surgical staging of carcinoma of the cervix laparoscopically. PMID- 1427399 TI - Description of a spheroid model for the study of radiation and chemotherapy effects on hypoxic tumor cell populations. AB - The presence of poorly oxygenated cells in solid tumors may account for clinical resistance to ionizing radiation and some chemotherapy in many cancers. Studies of the presence and spatial distribution, sensitivity to cancer therapies, and other physiological characteristics of hypoxic cells are hindered by the lack of markers specific for hypoxia and a relevant yet easily manipulated model system. We have chosen to use multicellular spheroids composed of murine EMT6 (fibrosarcoma) tumor cells as a model system and have applied an immunohistochemical marker specific for hypoxic cells with the ultimate goal of determining how cell populations change in response to radiation and/or chemotherapy. Large spheroids (500-700 microns in diameter) were selected and incubated in the presence of a hexafluorinated 2-nitroimidazole derivative, designated CCI-103F, which undergoes reductive metabolism and irreversibly binds to cellular macromolecules only under low oxygen tensions. A rabbit polyclonal antibody raised against a CCI-103F/protein adduct was used to visualize hypoxic cells using standard streptavidin-biotin-peroxidase immunohistochemical methods. Investigations using this spheroid model system promise to further our understanding of hypoxic cell resistance to cytotoxic therapies and of hypoxic cell biology in general. PMID- 1427400 TI - The specialty of gynecologic oncology as perceived by the public. AB - The purpose of this study was to obtain information about the public's awareness and perception of the discipline of gynecologic oncology. The marketing of cancer care and related services has resulted in substantial funding being allocated to market individual institutions. However, little has been done to educate patients to the fact that there are physicians specifically trained who possess special expertise in the care of specific types of malignancy. The members of The Division of Gynecologic Oncology at The Hospital of the University of Pennsylvania asked each new patient to complete an anonymous questionnaire hoping to learn more about her prior knowledge of the specialty of gynecologic oncology and her perceptions of our discipline. Presented is the analysis of the answers provided by the 200 participants. The conclusion is that the public in general is poorly informed of gynecologic oncology as a specialty and consequently may not be taking advantage of optimal cancer care already available. Thus, as a specialty we must institute programs to educate and enlighten patients. PMID- 1427401 TI - Chemotherapy of ovarian cancer: is longer better? PMID- 1427402 TI - Transition from benign to malignant epithelium in mucinous and serous ovarian cystadenocarcinoma. AB - The slides of all patients with ovarian cystadenocarcinoma treated at the University of Kentucky Medical Center from 1966-1990 were reviewed. Fifty-four serous tumors and 42 mucinous neoplasms were identified for further study. Benign epithelium adjacent to an area of borderline or malignant epithelium was observed in 74 tumors (79%) and a site of epithelial transition was noted in 38 cases (40%). The presence of associated benign epithelium was more common in borderline or well-differentiated lesions and in patients with early-stage disease. These findings are consistent with epidemiologic and molecular genetic data and suggest that certain benign serous or mucinous ovarian tumors have the potential for malignant transformation. Removal of these tumors, particularly in postmenopausal women, should result in a subsequent reduction in the frequency of ovarian cancer. PMID- 1427403 TI - The plasminogen activator urokinase and its inhibitor PAI-2 in endometrial cancer. AB - Invasion and metastasis of malignant cells require the disruption of the extracellular matrix, degradation of basement membranes, and intrusion into connective tissue and vascular and lymphatic spaces. Several studies have indicated a role for urokinase (u-PA) in proteolysis of the extracellular matrix and hence in stromal invasion and metastasis. Many malignant cells are known to secrete u-PA. Plasminogen activator inhibitor-type 2 (PAI-2) is an inhibitor of u PA and is present in several neoplastic cell lines and malignant ascites. We measured u-PA and PAI-2 antigen in tissue homogenates of normal and malignant endometrium from 21 postmenopausal patients. Enzyme-linked immunoassays which measure the bound and unbound, single-and two-chain form of the activator and bound and unbound form of the inhibitor were used. Urokinase was present in four of seven normal (range, 0.15-0.5; median, 0.15 ng/mg protein) and in significantly higher concentrations in all malignant endometrial homogenates (range, 0.41-9.2; median, 3.4 ng/mg protein), P < 0.001. PAI-2 was detectable in four of seven normal endometrial homogenates at low concentrations (range, 1.1 3.1; median, 1.1 ng/mg protein) and in all malignant tissue homogenates at significantly higher levels (range, 1.6-27.3; median, 4.9 ng/mg protein), P < 0.01. Levels of endometrial PAI-2 were higher in stages IC or greater compared to those in stages IA and 1B cancers (P < 0.05). PAI-2 may be useful as a prognostic marker in endometrial cancer. PMID- 1427404 TI - The effect of prolonged cisplatin-based chemotherapy on progression-free survival in patients with optimal epithelial ovarian cancer: "maintenance" therapy reconsidered. AB - From 1978 until 1988, 116 patients with epithelial ovarian cancer were entered onto one of three consecutive prospective clinical trials involving cisplatin based combination chemotherapy. They had the following characteristics: (1) stage III or IV disease, (2) grade 2 or 3 tumors, and (3) optimally debulked tumors (residual disease < or = 2 cm). The purpose of the study was to investigate the influence of duration of chemotherapy on survival. The treatment plans were as follows: Trial 1, 12 cycles of cisplatin/melphalan (43 patients); Trial 2, 12 cycles of cisplatin/cyclophosphamide (24 patients); and Trial 3, 6 cycles of cisplatin/cyclophosphamide (49 patients). The total dose of cisplatin was 60 mg/m2 in the first trial and 50 mg/m2 in the second and third trials. Median survival times for the three groups were 58, 29, and 35 months, respectively (NS). Median progression-free survival (PFS) times were 37, 23, and 15 months, respectively (P = 0.0008). Combining patients from the first two trials, the median PFS for patients receiving 12 planned cycles of chemotherapy was 30 months versus 15 months for patients receiving 6 planned cycles (P = 0.0004). Using a forward stepwise Cox proportional hazard model, the use of 12 cycles of therapy and melphalan predicted increased PFS (P = 0.0001 and P = 0.0002, respectively). In view of these results, the lack of published data supporting the superiority of 6 over 12 cycles of chemotherapy, and the rather recent availability of less toxic maintenance therapy (i.e., carboplatin), we believe that a multiinstitutional trial comparing the 6-cycle regimen with more prolonged chemotherapy is justifiable. PMID- 1427405 TI - Endometrioid carcinoma of the ovary and endometriosis: the association in postmenopausal women. AB - Histologic material from 42 patients with endometrioid carcinomas of the ovary was reviewed. Ovarian endometriosis was present in 11 cases (26%) and 8 of these patients were postmenopausal. The exact site of transition from benign to malignant epithelium was observed in 4 cases. The clinical characteristics of patients with associated endometriosis were not significantly different from those without this finding except that endometriosis was present only in patients with Grade 1 or Grade 2 carcinomas. These data suggest that ovarian endometriosis in the postmenopausal patient has the potential to undergo malignant transformation and, when detected, should be removed surgically. PMID- 1427406 TI - Peritoneal cytology in patients with uterine cervical carcinoma. AB - We studied the relationship between cytological diagnosis of peritoneal washing and pathohistological findings in 97 cases of stage Ib and 103 cases of stage IIa or b cervical carcinoma. No positive cytology was found in 24 cases classified as pT1 by pTNM classification. Positive cytology was found in 8 out of 40 cases with retroperitoneal lymph node metastasis, 2 out of 5 cases with uterine corpus infiltration, and 3 out of 4 cases with ovarian metastasis. Negative cytology was often found even in cases with metastasis to several retroperitoneal lymph nodes, while positive cytology was also found in cases without metastasis. The mechanism of cervical carcinoma metastasizing to retroperitoneal lymph nodes may not be the same as that of spreading into the abdominal cavity. Many cases with positive peritoneal cytology tended to recur with peritoneal carcinoma as compared to those with negative cytology. The above findings indicate that chemotherapy, including intraperitoneal administration, is necessary in addition to radiation therapy for patients with cervical carcinoma with positive peritoneal washings. PMID- 1427407 TI - Morbidity and recurrence with modifications of radical vulvectomy and groin dissection. AB - Vulvar carcinoma has been managed in recent years with modifications of radical vulvectomy and groin dissection. Separate groin incisions, superficial inguinal lymphadenectomy, unilateral groin dissection, and wide excision have been utilized to reduce the morbidity of treatment. In this study, the surgical management of 82 patients with vulvar squamous cell carcinoma was reviewed in order to assess morbidity and risk of recurrence. A modification of radical vulvectomy and groin dissection was employed in 67 patients, while 15 patients underwent classical en-bloc vulvar and groin dissection. Wound complications of the vulva occurred in 1 of 12 patients undergoing hemivulvectomy, in 8 of 55 undergoing radical vulvectomy, and in 7 of 15 who had en-bloc vulvar resection and groin dissection (P = 0.01). Among the 46 patients undergoing bilateral groin dissection through separate incisions, groin breakdown, lymphocyst, and lymphedema occurred in 10 (22%), 7 (15%), and 7 (15%), versus 0, 1 (7%), and 2 (13%) of the 15 who had unilateral groin dissection. Modification of vulvar resection did not increase the risk of local recurrence. Groin recurrence developed in 2 of 15 patients who underwent en-bloc groin dissection and in 1 of 46 who underwent bilateral groin dissection through separate incisions. Two of 15 who had a unilateral groin dissection recurred in the contralateral groin. The risk of recurrence as well as morbidity following modifications of radical vulvectomy with groin dissection should be considered when planning treatment. PMID- 1427408 TI - Serum CA125 regression in epithelial ovarian cancer: correlation with reassessment findings and survival. AB - Findings at reassessment laparotomy and disease-free survival are reported for a group of patients with advanced-stage epithelial ovarian cancer who have had a complete clinical response to cytoreductive surgery and multiagent platinum-based chemotherapy. The predictive value of the number of chemotherapy cycles to achieve a serum CA125 of < 35 U/ml is compared to the predictive value of s, the rate of achieving a normal serum CA125. s is generated from an exponential regression model. This study suggests that s accurately predicts which patients have residual disease at reassessment laparotomy, who will be free of disease, and, of those in the latter group, who are at greatest risk to recur, as well as overall survival. If these observations are confirmed, physicians may base further therapeutic intervention on the basis of a calculated parameter following complete clinical response to first-line treatment rather than relying on findings at reassessment laparotomy. PMID- 1427409 TI - Localization and therapy of human cervical tumor xenografts with radiolabeled monoclonal antibody 1H10. AB - Murine IgG3 monoclonal antibody (Mab) 1H10, which recognizes a tumor-associated antigen expressed on the surface of more than 40% of human cervical carcinoma tissues, was used for in vivo localization and therapy of cervical tumor xenografts. A human cervical carcinoma cell line, CaSki, was used as our experimental tumor system. Mab 1H10 antigen expression on the surface of CaSki cells was found to be cell-cycle independent. The ability of Mab 1H10 F(ab')2 to bind to CaSki tumor xenografts was verified by direct immunohistochemical staining of thin tumor sections with a Mab 1H10-peroxidase conjugate. Radioimmunoscintigraphy of nude mice bearing CaSki tumors after iv administration of [131I]1H10 F(ab')2 showed clear tumor images 48 hr after Mab injection. Radiolabeled Mab 1H10 F(ab')2 was found to specifically localize in solid CaSki tumors 96 hr after antibody injection. Radioactivity in tumor tissue was 4 times higher than that in kidney tissue and over 6 times higher than that in liver tissue. Mab 1H10 F(ab')2 binding to xenografted CaSki tumors was 17 times greater than a control IgG3 F(ab')2 after 96 hr. Therapy of athymic mice bearing established CaSki tumors with three iv injections of 100 microCi [131I]1H10 F(ab')2 resulted in extensive tumor necrosis and significant suppression (p < 0.05) of tumor growth compared to that in control mice. These results indicate that Mab 1H10 F(ab')2 may be clinically useful for detection or treatment of cervical cancer. PMID- 1427410 TI - Parity-related prevalence of rhesus antigens among Mozambican parturients. AB - The potential risk of rhesus alloimmunization and the ensuing risk of fetal death with increasing parity were investigated in two groups of parturients; primiparous and grand multiparous (para > or = 5) women with liveborns. It was hypothesized that significantly fewer women of the latter than of the former group would be rhesus negative, since grand multiparity would be expected to be associated with an increased risk of late fetal death in rhesus-negative parturients. Primiparous (n = 390) and grand multiparous (n = 755) parturients with liveborns were studied in order to identify D- and Du-negative individuals. Sixteen out of 390 primiparas (4.10%) and 28/755 (3.71%) grand multiparas were D and Du negative. The difference did not reach statistical significance. It appears that being a D- and Du-negative grand multiparous parturient, in the absence of anti-D prophylaxis, is not a significant reproductive disadvantage to being primipara in terms of an increased risk of having stillborn babies. PMID- 1427411 TI - Serum progesterone and 17-hydroxyprogesterone in the diagnosis of ectopic pregnancies and the value of progesterone replacement in intrauterine pregnancies when serum progesterone levels are low. AB - The corpus luteum function was evaluated in patients with surgically confirmed ectopic pregnancy (EP) in a multicenter study. In addition, the minimal threshold of serum progesterone (P) concentration required for salvaging intrauterine pregnancies (IUP) was also examined. Results show that single P or 17-OHP measurements are not diagnostic for EP, since mean P levels in EP were similar to those with spontaneous abortion though significantly lower than those in controls. 17-OHP levels in EP overlapped in 50% with IUP, and the mean levels were significantly lower only at 6-7 weeks. The 17-OHP levels when compared to hCG supports the view that corpus luteum defect is primary. In IUP, P levels < 8 ng/ml still were associated with viable (60%) pregnancy; thus no minimal threshold could be established. PMID- 1427412 TI - Role of rhesus alloimmunization in the etiology of late fetal death in Maputo. AB - Grand multiparous parturients with unexplained late fetal death (n = 70) and with surviving newborns (n = 755) were analyzed and compared regarding blood group in general and presence of D and Du antigens in particular. In the stillbirth group, none of the parturients had any signs of disease (syphilis, preeclampsia, placental abruption, severe anemia or fever) that could be associated with the fetal death. It was found that none of the parturients with stillbirth were D- and Du-negative while 28/755 (3.71%) of parturients with liveborn babies were D- and Du-negative. It is concluded that, among grand multiparous parturients with otherwise unexplained late fetal death, the risk of having fetomaternal rhesus incompatibility as stillbirth etiology is insignificant. The advantage of introducing anti-D immunoglobulin for prophylaxis against rhesus alloimmunization would presumably be insignificant. PMID- 1427414 TI - Low-dose aspirin in primigravidae with positive roll-over test. AB - In a prospective, randomized, double-blind study for the prevention of pregnancy induced hypertension and preeclampsia, 41 primigravidae with positive roll-over test (28th-32nd week of pregnancy) received 80 mg aspirin/day or placebo until the end of the 37th week. In the patients treated with acetylsalicylic acid (n = 22), 3 cases of proteinuria occurred, but no hypertensive pregnancy complication. In the placebo group (n = 19), 10 patients developed pregnancy-induced hypertension (6 of them preeclampsia). Group-specific differences concerning the occurrence of hypertension were statistically highly significant (p = 0.0004). No relevant differences were observed with regard to pregnancy duration, birth weight and umbilical artery pH value. The placebo group included 1 intrauterine death. No increased tendency to maternal or fetal bleeding was noticed. PMID- 1427413 TI - Effect of smoking on fibronectin production by human amnion and placenta. AB - Fibronectin production from amnion and placental tissues was evaluated in pregnant woman smokers and nonsmokers in order to examine if there were alterations of fibronectin metabolism in intrauterine tissues. In both amnion and placental tissues, cycloheximide inhibited the fibronectin output indicating that it was being synthesized. Mean fibronectin output by amnion in pregnant woman smokers was significantly lower than that in pregnant woman nonsmokers. In contrast, in the placenta from pregnant woman smokers, the output was significantly higher than that in pregnant woman nonsmokers. The present observations indicate that smoking alters an important biochemical constituent in amnion and placenta, possible leading to some complications. PMID- 1427415 TI - Beta-endorphin in amniotic fluid in normal and hypertensive gestations: relationship with maternal blood pressure parameters. AB - beta-Endorphin (beta-E) immunoreactivity was measured in the amniotic compartment of 52 normotensive and 45 hypertensive gestations. All the fetuses of the normal group were healthy and showed appropriate intrauterine growth, whereas only suffering and growth-retarded fetuses were included in the pathological group. As expected, amniotic beta-E concentration was found to be significantly higher in hypertensive than in normotensive pregnancies (mean +/- SEM: 129.1 +/- 8.15 vs. 59.1 +/- 2.68 pg/ml; p < or = 0.005). A positive correlation between the hormone levels and the diastolic as well as the mean maternal blood pressure (r: 0.554; p < or = 0.05 and r: 0.525; p < or = 0.05, respectively) was present only in pregnancies complicated by hypertension. Furthermore, a negative correlation (r: 0.555; p < or = 0.05) linked amniotic beta-E and the pulse pressure in normal but not in complicated pregnancies. Unless beta-E in the amniotic compartment is also of amniochorial origin, our results suggest that the fetal endorphinergic tone is either activated by elevated diastolic and mean maternal pressure levels or lowered by increased pulse pressure values in normally elapsing pregnancies. PMID- 1427416 TI - Uteroplacental Doppler velocimetry during Braxton Hicks' contractions. AB - Pulsed-wave Doppler ultrasound was used to evaluate the influence of Braxton Hicks' contractions on flow velocity waveforms in the uterine arteries. Flow velocity waveforms were obtained from a standardized site, at the crossing of the uterine artery with the external iliac artery near the uterine wall. Doppler signals were recorded in 16 healthy near-term nulliparous pregnant women. During Braxton Hicks' contractions, a considerable increase in pulsatility index (PI) was found in the uterine arteries increasing from 0.71 +/- 0.21 (mean +/- SD) to 1.14 +/- 0.67 (p < 0.005). Maternal heart rate decreased slightly but significantly during contractions. Despite the high PI values that were found during Braxton Hicks' contractions, a diastolic notch in the flow velocity waveform was never noticed. The findings indicate that during Braxton Hicks' contractions, resistance to blood flow in the uteroplacental circulation is considerably increased. PMID- 1427417 TI - Maternal plasma and milk free cortisol during the first 3 days of breast-feeding following spontaneous delivery or elective cesarean section. AB - In a view of the increased clinical interest in the presence of hormones in human milk, the objective of this study was to evaluate maternal plasma and milk cortisol levels in early puerperium and their relationship in breast-feeding in women who underwent elective cesarean section or who delivered vaginally. During the first 3 days of breast-feeding, plasma and milk cortisol levels declined significantly both in women who underwent elective cesarean section and in women who had spontaneous deliveries. Moreover, the breast-feeding procedure did not affect maternal plasma and milk hormonal levels, since no differences between the cortisol levels measured immediately before and after morning daily breast feeding were detected. Furthermore, a very high positive correlation (p < 0.001) was found between plasma and milk cortisol concentrations. Therefore, maternal plasma cortisol levels can be considered a very reliable measure to predict the hormonal concentration in breast milk. PMID- 1427419 TI - Perinatal audit of one hundred consecutive vacuum extractions in Maputo. AB - The extraordinary demands on obstetrical services that prevail in many developing countries necessitate critical reviews of existing norms for obstetrical management. Vacuum extractions were studied in this context as a part of the regular perinatal audit carried out at the Maputo Central Hospital, the only hospital in Maputo with emergency surgery catering to the 43,000 annual deliveries. Extractions performed with the fetal head above the ischiatic spines were associated with a high number of complications and an 81% risk of neonatal asphyxia and also with a number of severe neonatal traumas. The risk of intracranial hemorrhage tended to be higher with extractions of fetuses with the head at or above the ischiatic spines, particularly when there was concomitant intrapartum asphyxia. It is concluded that a frequent perinatal audit of selected risk deliveries is a useful monitoring tool for examining prevailing indications for various obstetric interventions. PMID- 1427420 TI - Neuropeptide Y, its localization in the human cervix and possible effect on the contractile activity of cervix smooth muscle. AB - Immunochemical methods were used to identify neuropeptide Y (NPY) in the cervical tissue of women at early and term pregnancy. NPY-containing fibers could not be demonstrated in the upper and lower uterine segments at term, but the cervical innervation persisted during labor. Moreover, NPY alone did not affect cervical contractile activity, although the stimulatory effect of noradrenaline was enhanced. PMID- 1427418 TI - Suppression of human chorionic gonadotropin in the human placenta at term by human thyroid-stimulating hormone in vitro. AB - Human chorionic gonadotropin (hCG) exerts a clinically apparent negative feedback on the secretion of human thyroid-stimulating hormone (hTSH) in pregnancy, and the two have cross-reactivity for the TSH receptor in membrane preparations of the thyroid. We examined whether hTSH, in turn, has an influence on the secretion and synthesis of hCG in short-term cultures of human placenta at term. A dose- and time-dependent decrease in the extracellular hCG concentration caused by hTSH was demonstrated. To examine whether hTSH inhibits de novo synthesis of hCG or decreases hCG depletion, we determined the amount of hCG secreted and the size of the intracellular pool by using an enzyme immunoassay. By incorporating a radiolabeled amino acid in the hCG molecule, we measured the amount of hCG synthesized de novo. We concluded that hTSH acts by decreasing the rate of de novo synthesis of placental hCG. PMID- 1427421 TI - Effect of the short follicular phase on subsequent conception. AB - The present study was designed to evaluate whether there is a lower pregnancy rate in women with short follicular phases, as defined by attaining the peak estradiol level before day 11 of the cycle. Thirty-two early ovulators with mature follicles were matched with 32 women being treated for similar infertility problems, who ovulated between days 12-20. Pregnancies were achieved by 9 (28.1%) of the early ovulators compared to 19 (59.4%) of the controls. The mean number of cycles required to achieve a pregnancy was 8.6 in the early ovulators compared to 6.4 in the controls. Using the clinical life table method, the 12-month pregnancy rate was estimated to be 31.4% for early ovulators as compared to 66.3% for controls. Whether lengthening the follicular phase by drug treatment will improve pregnancy rates remains to be seen. PMID- 1427422 TI - Influence of valve surgery on female fertility. AB - Pregnancies following cardiac valve surgery represent a considerable maternal and fetal risk. The present paper is a report of 163 women in child-bearing age who underwent cardiac valve surgery. Congenital (14.7%) and acquired (85.3%) cardiac defects required a total of 72 alloplastic and 16 bioprosthetic valve implantations. In 69 patients, purely instrumental correction was performed, in 6 patients conduits were placed. Thirty-four pregnancies were observed and led to the delivery of 18 healthy infants. The birth weight was always in the 2-sigma normal range or slightly above. Three cesarean sections were performed due to the cardiac defect, in 6 patients vacuum extraction or forceps delivery was done, and in 9 patients delivery was spontaneous. We observed 4 cases of spontaneous abortion, and in 12 cases interruption of pregnancy. 75.1% women never became pregnant. Potential risks in terms of endocarditis, repeated valve implantation and anticoagulation are emphasized, methods to decrease the physical strain during delivery are discussed. PMID- 1427423 TI - McRoberts maneuver for the management of the aftercoming head in breech delivery. AB - A case report of breech delivery complicated by entrapment of the aftercoming head is presented. McRoberts maneuver was applied to facilitate the release of the head. It is suggested that the same theoretical basis that stands behind the use of McRoberts maneuver in shoulder dystocia might make it applicable as one of the maneuvers to release the aftercoming head in breech delivery. PMID- 1427424 TI - Retrohymenal vaginal atresia with perforate transverse vaginal septum. AB - A transverse vaginal septum is the most common congenital anomaly of the vagina. Vaginal atresia is seen less frequently. There have been some variations in cases of transverse vaginal septum and vaginal atresia. This is the first report of a patient with retrohymenal vaginal atresia and perforate transverse vaginal septum. PMID- 1427425 TI - POEMS: a multifactorial syndrome. PMID- 1427426 TI - A prospective comparison of alpha-IFN and conventional chemotherapy in Ph+ chronic myeloid leukemia. Clinical and cytogenetic results at 2 years in 322 patients. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. AB - BACKGROUND: Standard or conventional treatment of chronic myeloid leukemia (CML) had little effect on the course and the duration of the disease. Treatment with human natural and recombinant alpha-interferon (IFN) was shown to induce hematologic responses, together with partial or complete repopulation of the marrow with Ph negative cells (karyotypic response). These findings prompted a prospective comparison of IFN and conventional treatment in CML. METHODS: A multicenter prospective controlled study in previously untreated or minimally treated chronic phase Ph+ CML was employed: 322 patients were recruited between 1986 and 1988 and assigned to treatment with human recombinant alpha-IFN (Roferon A) or hydroxyurea, with a randomization ratio of 2:1. The results of the first 2 years of treatment were analyzed and compared, based on the intention-to-treat policy. RESULTS: From 8 mo of treatment on, hematologic and karyotypic responses (KR) were more frequent and better in the IFN arm than in the CHT arm. Overall, a major KR (Ph neg greater than 66%) was achieved at least once in 35/218 (16%) IFN treated patients vs 1/104 CHT-treated ones (P less than 0.0001). None of these 36 patients has progressed from chronic to blastic phase as yet. After 2 years of treatment, 21 of 218 IFN patients (10%) had a major KR vs 1 of 104 CHT patients (P = 0.003), and the cumulative proportion of blastic metamorphosis was 19% in the IFN arm vs 27% in the CHT arm (P = 0.17). Side effects were more frequent in the IFN arm, but compliance with the treatment policy was identical in both arms. The treatment cost was about 11 US dollars per patient per month in the CHT arm, and 200 times higher in the IFN arm. CONCLUSIONS: During the first 2 years of treatment, IFN was more expensive, had more side effects, but was more effective than CHT in terms of hematologic and karyotypic responses. PMID- 1427427 TI - Molecular characterization and functional studies on Hb Kempsey, beta 99 (G-1) Asp----Asn, a high-oxygen affinity variant. AB - BACKGROUND: Hb Kempsey (beta 99 Asp----Asn) is a high-oxygen affinity hemoglobin, never before reported in Italy, associated with secondary erythrocytosis. It has been found in the heterozygous state in two subjects from the same family originating from the Verona area in Northern Italy. METHODS: The abnormal hemoglobin was studied both at the protein and at the DNA level. The amino acid substitution was identified by fingerprinting and amino acid analysis. The nucleotide replacement was investigated by means of polymerase chain reaction (PCR) of the beta gene and direct sequencing. Oxygen affinity and other functional parameters were assessed on whole blood and on the separate hemoglobin fractions. RESULTS: These studies allowed us to establish the molecular substitution GAT (Asp)----AAT (Asn) at codon 99. Functional studies revealed a left-shifted and biphasic dissociation curve of the proposita, with a very low p50. The two carriers of this hemoglobinopathy have different degrees of polyglobulia, since iron deficiency in one of them reduces total and abnormal Hb. CONCLUSIONS: The compensatory mechanisms for tissue hypoxia are discussed with the conclusion that erythrocytosis has to be preserved in these patients to maintain adequate tissue oxygenation. PMID- 1427428 TI - Volumetric changes in phorbol myristate acetate activated neutrophils: a rapid and simple assay using Coulter counter STKR and STKS hematological analyzers. AB - BACKGROUND: The aim of this study was to investigate some physical changes (volume, conductivity and scatter) in human polymorphonuclear leukocytes (PMN) activated with phorbol myristate acetate (PMA). METHODS: Volume changes in PMA activated neutrophils were assayed by both STKR and STKS, two Coulter hematological analyzers. Scatter changes in PMN activated by PMA in suspensions containing nitro-blue tetrazolium (NBT) were investigated on STKS scattergrams. RESULTS: PMA activation induced PMN volumetric increases that could be assayed with STKR and displayed with STKS. The activation of PMN in suspension containing NBT induced cellular scatter changes on STKS scattergrams. The differences in scatter between resting and PMA-activated neutrophils may thus provide a semiquantitative assay of NBT reduction and superoxide production. Volume changes in PMA-activated neutrophils were due to cellular swelling through water uptake, induced by Na+/H+ antiport activation and Na+ influx. Since volume changes in PMA activated neutrophils might occur without O2- production and vice versa, in the cases in which PMA activation of protein kinase C cannot be demonstrated by O2- production, the effect of PMA on protein kinase C- mediated Na+/H+ antiport activation, and in turn on PMA volume changes, reflects protein kinase C activation. CONCLUSIONS: A screening of neutrophils unresponsive to volumetric changes from PMA activation may be easily performed using both Coulter STKR and STKS analyzers, whereas expected or defective PMA-induced production of O2- may be semi-quantitatively evaluated by STKS. PMID- 1427429 TI - Presence and significance of cold agglutinins in patients with HIV infection. AB - BACKGROUND: HIV-infected patients may contract a variety of other concurrent infections, including Mycoplasma pneumoniae, cytomegalovirus (CMV) and Epstein Barr virus (EBV), that are known to be causes of transient cold agglutinins (CA). The aim of this study was to search for the prevalence, the persistence and the significance of CA in HIV antibody-positive patients. METHODS: Ninety patients belonging to different risk groups (drug addicts, homosexuals and hemophiliacs), including 15 with AIDS, 20 with ARC, 25 with PGL, 30 symptom-free individuals and 100 healthy blood donors were assessed for the presence of CA for at least six months. RESULTS: In 20 cases (22%) CA were found: 3, 7, 5 and 5 respectively, in each of the above mentioned HIV-positive groups, while the group used as control was CA-negative. There were no differences between CA-negative and CA-positive patients with regard to the presence of anemia, frequency of other infections, or development of lymphatic malignancy during the follow-up period. Serological specificity of CA included 14 of type anti-I, 5 of anti-i and 1 of anti-Pr specificity. CONCLUSIONS: It appears that CA production is another immune disorder of patients with HIV infection. PMID- 1427431 TI - Thymic dysfunction in childhood T-acute lymphoblastic leukemia: a possible linkage with a primary thymus involvement. AB - Experimental models, clinical and histopathological observations suggest a thymic origin of childhood T acute lymphoblastic leukemia (T-ALL). We studied thymic epithelial function in childhood T-ALL as compared to normal controls in order to improve our understanding of the cellular immunodeficiency mechanisms operating in a thymus-linked malignant process. The levels of Facteur Thymique Serique (FTS) were measured in 9 patients at diagnosis, according to the rosette inhibition assay of Dardenne & Bach (1975). This method is based on the capacity of human serum containing FTS activity to confer on rosette-forming cells (RFC) from adult thymectomized mice a sensitivity to azathioprine identical to that of normal mouse RFC. All patients presented low age-corrected titres of FTS. No zinc deficiency was found, suggesting that low FTS levels are not related to unexpressed FTS biological activity. Plasma from all the children studied contained factors capable of inhibiting the biological activity of FTS in vitro. However, the nature of this inhibitor has not yet been elucidated. Our study shows the presence of a thymic dysfunction in childhood T-ALL, which could partially explain the immunodeficiency described in these patients. The linkage of the leukemic process with a primitive thymic involvement is discussed. PMID- 1427430 TI - Effect of cyclosporin A on T cell clones from severe aplastic anemia: differential sensitivity of TNF and GM-CSF production. AB - In this study we have analyzed the activity of Cyclosporin A (CsA) on the "in vitro" production of TNF and IL-3/GM-CSF as a preliminary basis for explaining the successful use of CsA in aplastic patients. Thus, 73 T cell clones, obtained by a limiting dilution technique from the peripheral blood and bone marrow of 3 patients with severe aplastic anemia (SAA), were studied for TNF and IL-3/GM-CSF production as induced by stimulation with 1% PHA plus 1 ng/ml TPA. Lymphokines obtained in this manner were then tested by biological assays. Twelve out of the initial 73 T cell clones were selected for the production of a large quantity of IL-3/GM-CSF and/or TNF. With these clones we studied the ability of CsA to inhibit TNF and IL-3/GM-CSF production, which was stimulated with specific monoclonal antibodies directed against the CD2 and CD3 surface antigens. TNF and IL-3/GM-CSF production displayed a different sensitivity to CsA inhibition. In fact, at 400 ng/ml CsA a residual production of IL-3/GM-CSF was present in all clones tested (CD3: 21.8% and CD2: 14.4% of the maximal IL-3/GM-CSF activity), while secretion of TNF was virtually abrogated at 100 ng/ml. Moreover, the mean ID50 for TNF production was significantly lower than that of IL-3/GM-CSF (CD2: p = 0.028, CD3: p = 0.01). Using specific anti-IL-3 and anti-GM-CSF monoclonal antibodies, we showed that only GM-CSF, and not IL-3, was resistant to CsA inhibition. In conclusion, these results may represent a possible explanation of the successful use of CsA in the treatment of some patients with SAA. PMID- 1427432 TI - Fulminant sepsis in adults splenectomized for idiopathic thrombocytopenic purpura. AB - BACKGROUND AND METHODS: Splenectomy is still a mainstay in the treatment of idiopathic thrombocytopenic purpura (ITP). Although the risk of fulminant sepsis after splenectomy in children and in adults has been known for a long time, the true prevalence of fulminant sepsis in adults splenectomized for ITP has still not been well established, despite many anecdotal reports. In this paper we have tried to estimate this risk by reviewing the available literature and by analyzing a large cohort of adults splenectomized for ITP at our Institute since 1970. RESULTS: Two cases of fulminant sepsis (a 21-year-old man and a 24-year-old woman) were traced in a group of 133 splenectomized adults, with a crude incidence of 1.5% or, equivalently, of 0.17 cases per 100 patient-years. No case of sepsis occurred in a control group of 323 non splenectomized ITP adults. This estimation seems sufficiently precise for the large population analyzed and the duration and completeness of follow-up (1,126 patient-years, mean 101 months, 2 patients lost from follow-up), and it is in agreement with the estimations yielded by a literature review (1.8%). CONCLUSIONS: The risk of fulminant sepsis seems to be a real hazard in adults splenectomized for ITP, and a conservative approach in recommending splenectomy seems advisable. Antipneumococcal vaccination should also be recommended. PMID- 1427433 TI - Bone marrow transplantation for childhood leukemia: five years' experience in a pediatric hematology center. AB - BACKGROUND: Fifty-three children (39 male, 14 female, median age 9 years 3 months) with different forms of leukemia underwent bone marrow transplantation (BMT) at our center. Various conditioning regimens were used according to the disease and time of BMT. In this paper we evaluate the impact of the experience of a pediatric hematology center on BMT-related problems in children. METHODS: We analyzed disease-free survival (DFS), early BMT-related effects, hepatic, cardiac and respiratory function and late endocrine effects as shown by standard instrumental and laboratory tests. RESULTS AND CONCLUSIONS: Outcome (overall median follow-up 34 months) was satisfactory. Three years DFS was 50.1% in all patients, 58.8% in lymphoblastic leukemia in 2nd complete remission (CR), and 50.0% in acute myeloid leukemia (some in 2nd or subsequent CR). Three of four patients with chronic myeloid leukemia were alive at 38 months. Management of the problems causing early post-BMT toxicity contributed to a progressive fall in early morbidity and mortality (14.3% in the last 3 years). Pre-BMT hepatitis in most patients was not associated with increased post-BMT hepatotoxicity. Cardiac function, even in patients given aggressive anthracycline treatment before BMT, remained normal 3 years after transplantation, as did respiratory function, although 8 cases presented subclinical restrictive and/or obstructive alterations. Compensated hypothyroidism was observed in 9 patients. Six boys received replacement treatment for hypogonadism. Severe height impairment was seen in 2 patients. Post-BMT endocrine and growth effects require a longer follow up for definitive conclusions to be drawn.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427434 TI - Uveitis, a presenting symptom of malignant histiocytosis. AB - A patient presenting initially with bilateral uveitis was admitted 6 weeks later to the Department of Internal Medicine "A" because of fever, chills, and pancytopenia. Physical examination, ultrasonography and CT scan revealed hepatosplenomegaly only, without lymphadenopathy. A bone marrow trephine biopsy showed areas with a dense infiltrate of abnormal cells, displaying many mitotic figures. Some of the cells resembled better differentiated histiocytes and contained hemosiderin pigment or phagocytosed erythrocytes. Immunohistological tests confirmed the diagnosis of malignant histiocytosis (MH). A survey of the literature revealed two other cases with uveitis and MH. PMID- 1427435 TI - Chronic neutrophilic leukemia (CNL) with karyotypic abnormalities associated with plasma cell dyscrasia: a case report. AB - A case of chronic neutrophilic leukemia (CNL), a rare myeloproliferative syndrome associated with monoclonal gammopathy of uncertain significance (MGUS-Type IgGk), is reported. Karyotypic study, carried out on bone marrow, excluded Philadelphia pos. chronic myeloid leukemia (CML) and showed Y loss (45 XO). Only a few cases of CNL with paraproteinemia have been reported, but no case of associated karyotypic abnormalities and paraproteinemia has so far been described. PMID- 1427436 TI - Efficacy of liposomal amphotericin B (AmBisome) in the eradication of Fusarium infection in a leukaemic patient. AB - We recently succeeded in eradicating a Fusarium infection by treatment with liposomal amphotericin B (L-AmB). The patient, a 22-year-old man with acute lymphoblastic leukaemia (ALL), developed fever and diffuse cutaneous maculopapular necrotising nodules during post-chemotherapy neutropenia. Fusarium verticilloides was isolated from the skin, and hyphae were observed on direct microscopy. Despite increased WBC and amphotericin B (AmB) treatment (0.7 mg/kg/day for 11 days), he remained febrile and a chest X-ray revealed pulmonary lesions. Fusarium infection was confirmed by bronchial aspirate. AmB was increased to 1 mg/kg/day, and continued for 16 days (total dose 1630 mg). A slight improvement was observed at tomography, but nephrotoxicity developed. Treatment was changed to L-AmB (3 mg/kg/day). The patient received this drug for 20 days (total dose of 3850 mg) with complete regression of the pulmonary lesions. No adverse event occurred, and nephrotoxicity resolved. The patient was discharged from hospital cured of the Fusarium infection and in clinical and haematological remission. No relapse of fusariosis occurred, despite additional courses of intensive chemotherapy. Ambisome could represent an important advance in antifungal treatment since it allows aggressive treatment and eradication of mycoses refractory to conventional therapy while avoiding renal toxicity. PMID- 1427437 TI - AIDS-related complex treated by antiviral drugs and allogeneic bone marrow transplantation following conditioning protocol with busulphan, cyclophosphamide and cyclosporin. AB - A 26-year-old man with AIDS-related complex (ARC) was treated with high-dose busulphan and cyclophosphamide, followed by allogeneic bone marrow transplantation. For 3 months before transplantation he received a combination of four drugs considered active against human immunodeficiency virus (HIV) to reduce the viral burden: zidovudine, acyloguanosine, fusidic acid and phenylidantoin. Although in reduced doses in coincidence with marrow engraftment, zidovudine therapy was scheduled after transplantation in order to protect donor cells from infection with HIV. Engraftment rapidly occurred and was documented by cytogenetic analyses. The post-transplant course was characterized by severe acute GvHD with irreversible hepatorenal failure. The patient died on day 48 after transplantation. Polymerase chain reaction analyses for detecting HIV DNA showed the persistence of positivity at day +30 and +45 after transplantation. Antibodies to specific HIV proteins evaluated with Western blot testing also persisted at days +21 and +35 after transplantation. Circulating immunocomplexes disappeared on day +31, and an increase in the CD4/CD8 ratio occurred. The short survival of the patient, affected by chronic hepatitis too, does not allow final conclusions about the role of BMT in HIV disease. PMID- 1427438 TI - Hb Lepore in Campania: a study using a rapid molecular approach. PMID- 1427440 TI - Lymph node blast crisis in chronic myeloid leukemia mimicking T-immunoblastic lymphoma. AB - BACKGROUND: Chronic myeloid leukemia arises from a somatic mutation in a pluripotent stem cell. It generally terminates with a blastic crisis (BC). One third of BC are lymphoid, and most have a pre-B phenotype. Few cases of T lymphoid BC have been reported. Here we describe a lymph node blast crisis mimicking T-immunoblastic lymphoma. METHODS: Bone marrow and lymph nodes were histologically examined by standard methods and by an immunoperoxidase technique. Cytogenetic studies were also performed on lymph node and blood cells. Analysis of T-cell receptor genes and BCR rearrangements were performed on DNA extracted from both frozen bone marrow and lymph-node cells. RESULTS: Lymph-node histology showed an infiltration by large lymphoid blasts, consistent with a diagnosis of immunoblastic lymphoma. Blast cells were CD2, CD7, TDT positive, and negative for myeloid and mature lymphoid antigens. The Ph1 chromosome was found in both bone marrow and lymph-node cells. BCR rearrangement was found in the DNA from both bone marrow and lymph-node cells. TCR genes were not rearranged. DISCUSSION: The present study provides strong evidence that the lymph-node blast crisis of CML can assume the morphological appearance of immunoblastic lymphoma and may retain the immunological phenotype and genetic features of early T cells with BCR rearrangements. PMID- 1427439 TI - Primary thrombocythemia: new drugs for an evolving disease. PMID- 1427441 TI - Therapy with Anagrelide in patients affected by essential thrombocythemia: preliminary results. AB - BACKGROUND: Anagrelide, an imidazo-quinazolin compound first proposed as a potent inhibitor of platelet function, was subsequently recognized as a drug able to lower the platelet number both in normal subjects and in myeloproliferative syndromes with thrombocytosis. We report our experience with Anagrelide therapy in 20 patients affected by essential thrombocythemia (E.T.). PATIENTS AND METHODS: Twenty consecutive patients with E.T. entered the study from June, 89 to July, 91. Therapy schedule was as follows: 0.5 mg every 12 hours for 7 days; subsequently the daily dose was increased by 0.5 mg/day every week until a response was obtained (a decrease of the platelet count to less than 500 x 10(9)/l = complete response; to less than 600 x 10(9)/l = partial response). RESULTS: Of 19 evaluable patients, complete response (CR) was obtained in 13 (68%) and partial response (PR) in 3 (16%). For all responders, the mean time to response was 5.2 months: mean daily dose of Anagrelide 2 mg. Side effects were recorded in 8/20 patients (40%): tachycardia (n = 4), gastrointestinal distress (n = 3), perimalleolar edema (n = 1). In 6 cases therapy was discontinued definitively. DISCUSSION: Response rate to therapy with Anagrelide is similar to that with alkylating agents and alpha 2b-recombinant interferon; furthermore, Anagrelide is a drug without cytotoxic properties. The mean daily dose able to obtain a response is 2 mg, but maintenance therapy at similar doses is always necessary. In conclusion, we can say that Anagrelide is an effective drug in the treatment of patients with E.T., but its side effects must be seriously considered. A larger study may show whether it should be considered as a "first line" drug for all patients with E.T. PMID- 1427442 TI - In vitro inhibition of interferon alpha-2a antiproliferative activity by antibodies developed during treatment for essential thrombocythaemia. AB - BACKGROUND: Various authors have reported the development of anti-interferon (IFN) antibodies following IFN-alpha treatment for haematological malignancies. So far the methods for detecting these antibodies have not considered the antiproliferative activity of this IFN, which is its most important property in anticancer therapy. METHODS: In this in vitro study we evaluated the ability of anti-IFN alpha-2a neutralising antibodies to inhibit the antiproliferative activity of IFN alpha-2a and lymphoblastoid IFN alpha using megakaryocyte colony growth as the revelatory system. These antibodies were detected in two patients affected by essential thrombocythaemia (ET) who lost their haematological response to IFN alpha-2a, but responded to a subsequent treatment with lymphoblastoid IFN alpha. RESULTS AND CONCLUSION: The results show that the inhibition of megakaryocyte colony growth induced by IFN alpha-2a was totally suppressed in the presence of the two ET patients' sera, whereas the inhibition induced by lymphoblastoid IFN alpha was not significantly affected. These in vitro data demonstrate the high specificity and activity of these antibodies on the antiproliferative effect of IFN alpha-2a. PMID- 1427443 TI - Ultrastructural, immunologic and clinical follow-up of five patients with HCL treated with interferon (IFN) for more than three years. AB - BACKGROUND: Treatment results in HCl have been improved by the use of alpha-IFN, which is now the standard first-line therapy for this disease, but the mechanism of IFN action is still unclear. It is known, however, that IFN is able to induce hematologic, immunological and phenotype membrane changes which parallel the patients' (pts) clinical response. The aim of our study was to correlate the clinical response to IFN treatment with ultrastructural and phenotype membrane changes in hairy cells (HCs), in order to elucidate the mechanism of IFN action at the cell level. METHODS: We assessed the phenotype membrane and ultrastructural changes induced in HCs by long-term alpha-IFN treatment in five pts with HCL; membrane-bound Il 2-R on PHA-stimulated PBL, the release of IL 2-R by PHA-stimulated PBL and the serum levels of s-IL 2-R were also determined in one pt. RESULTS: The surface immunological phenotype, mainly the HCL-related surface antigen CD25, changed after IFN treatment, dropping from abnormally high to normal values. Furthermore, IFN treatment induced ultrastructural changes in HCs, consisting mainly of a sharp reduction in, up to the almost complete disappearance of, the hairy projections: very few, if any, short, thick villi persisted. The ultrastructural changes in HCs paralleled clinical and hematologic response to IFN treatment in such a way that IFN alone may be considered the cause of these changes. As far as detection of the membrane-bound IL 2-R p55 chain on PHA-stimulated PBL is concerned, the expression of p55 is very high on the membrane of HCs; a high level of serum s-IL 2-R was also found in the HCL pt studied before IFN treatment, whereas the release of IL 2-R by PHA-stimulated PBL was higher than normal, but not significantly. Two of our pts, who did not respond or responded very poorly clinically to IFN treatment, should probably be considered cases of HCL "variants". CONCLUSIONS: The phenotype membrane and the ultrastructural changes in HCs very closely paralleled the patients' clinical responses to IFN, suggesting that both the immunologic and the morphologic changes induced in HCs by in vivo IFN treatment are a direct counterpart of its biologic effect. PMID- 1427445 TI - Early response to alpha interferon in a patient affected by hairy cell leukemia. AB - A 61-year-old splenectomized male patient affected by hairy cell leukemia (HCL) in relapse was treated with interferon (IFN) at a dosage of 3 x 10(6) U/day. After only 11 days of treatment, IFN was stopped because the patient developed fever, jaundice and respiratory distress. Upon recovery from this infectious episode, the patient was judged to be in complete remission of HCL on the basis of clinical and laboratory findings, and he remained off-therapy for 2 years. When an overt relapse occurred, the patient was again treated with IFN and, after a very short time, he achieved a new, good partial remission that is maintained 28 months later without treatment. This observation remains speculative for understanding the mechanism of action of IFN in other comparable HCL cases. PMID- 1427444 TI - The reconstitution of cellular immunity after bone marrow transplantation in children. PMID- 1427446 TI - Thrombocytopenic purpura during therapy with simvastatin. AB - The authors describe a case of very serious thrombocytopenic purpura occurring in a diabetic and hyperlipidemic woman during therapy with simvastatin, an HMG-CoA reductase inhibitor drug. Interruption of the medical treatment produced a prompt reversal of the thrombocytic attack: one year later the patient's platelet count remains within the normal range. The authors have not found other reports in the medical literature of similar serious reactions during therapy with an HMG-CoA reductase inhibiting substance; nevertheless, a causal nexus is hypothesized but not argued in this case, since further studies will be needed before this connection can be established. PMID- 1427447 TI - Feasibility of prenatal diagnosis of beta-thalassemia using two highly polymorphic microsatellites 5' to the beta-globin gene. AB - Short tandem repeats (STRs) are highly informative loci within the human genome, consisting of short nucleotide sequences tandemly repeated in variable numbers. This results in different alleles of variable length. Herein we describe two STRS located 5' to the beta-globin gene. They can be detected by non radioactive methods and may be used to make prenatal diagnosis of beta-thalassemia. PMID- 1427448 TI - Normal values of total reticulocytes and reticulocyte subsets in children and young adults. AB - This work provides the values for percentage and total reticulocyte count, as well as the values of reticulocyte fluorescence intensity ratios as determined by an automated fluorescent technique in a normal pediatric population. The peripheral reticulocyte subsets, as assessed on the basis of their degree of maturation, allow a more accurate evaluation of bone marrow activity than the percentage or total count do. This would result in a more appropriate management of erythropoietic disorders in children. PMID- 1427449 TI - Cytokine serum levels and acute graft versus host disease after allogeneic bone marrow transplantation. PMID- 1427450 TI - Alpha-interferon treatment of hairy cell leukemia and associated monoclonal large granular lymphocyte proliferation. PMID- 1427451 TI - RDW: a helpful diagnostic parameter in the malabsorption syndrome? PMID- 1427452 TI - Pulmonary embolism and intravenous high-dose desferrioxamine. PMID- 1427453 TI - B-cell chronic lymphocytic leukemia and plasma cell disorders in the same patient. Report of two cases. PMID- 1427454 TI - Reducing the haemorrhagic risk related to splenectomy in patients with severe chronic idiopathic thrombocytopenic purpura. PMID- 1427455 TI - Increase in the D-dimer levels during treatment in patients with acute myelogenous leukemia. AB - Plasma concentration of thrombin-antithrombin III complex (TAT), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-2, D dimer complex and urokinase-plasminogen activator (u-PA) activity were studied in 30 patients with acute nonlymphoblastic leukemia (ANLL), before and during antileukemic therapy. Fifteen patients showed signs of disseminated intravascular coagulation (DIC), 10 of them classified as M3, 2 as M2 and 3 as M5 subtypes. The initial levels of TAT complex were elevated in all ANLL patients. This increase was more pronounced in patients with DIC (p less than 0.05). TAT increased significantly during the treatment period in all cases. u-PA and PAI-1 levels were elevated but there were no statistically significant differences between patients with and without DIC. PAI-2 levels were below the limit of detection in controls and in patients. However, the initially elevated D-dimer complex levels were significantly higher in DIC cases (p less than 0.01) and they increased during the treatment period. A significant and positive correlation between D dimer and TAT complex values was found in DIC patients (r = 0.68, p less than 0.001). The high TAT complex and D-dimer levels further increased during chemotherapy treatment strongly suggest a hypercoagulable state with secondary activation of fibrinolysis not severe enough to manifest itself as clinically evident DIC in the majority of cases. PMID- 1427456 TI - Warfarin-induced skin necrosis in 2 patients with protein S deficiency: successful reinstatement of warfarin therapy. AB - Warfarin-induced skin necrosis is a rare but serious complication of oral anticoagulant therapy. This condition has been associated with protein C deficiency but only rarely reported in patients with a deficiency of protein S. We have managed 2 patients with a history of warfarin-induced skin necrosis who were diagnosed as being protein-S-deficient. Since both patients were candidates for long-term anticoagulant therapy we elected to reintroduce warfarin using a regimen designed to minimize the risk of recurrent skin necrosis. While they were therapeutically anticoagulated with heparin, warfarin was started at 1 mg/day and the dose was increased gradually. Heparin was not discontinued until the prothrombin times were in the therapeutic range for at least 72 h. Both patients tolerated the reinstitution of warfarin without difficulty and they have now been followed for over 2 years on oral anticoagulants without complication. PMID- 1427457 TI - Treatment of proximal deep-vein thrombosis using subcutaneously administered calcium heparin: comparison with intravenous sodium heparin. AB - In a prospective, randomized clinical trial we compared the efficacy of subcutaneously (SC) administered (every 8 h) calcium heparin to intravenous (IV) sodium heparin in the treatment of proximal deep-vein thrombosis (DVT). A secondary objective was to give enough heparin to achieve a therapeutic anticoagulant effect by the end of the first 24 h. Five of 36 patients (14%) in the SC heparin group failed to achieve a therapeutic anticoagulant effect by the end of the first 24 h compared to 2 of 23 patients (9%) in the IV group (p = NS; 95% CI for true difference = -11.7% to 22.1%). Two of 31 patients (6.5%) in the SC group had venographic evidence of clot propagation compared to 1 of 19 patients (5.3%) in the IV group (p = NS; 95% CI for true difference = -12.4% to 14.8%). The rate of major hemorrhagic complications was similar in each group (approximately 15%). We conclude: (1) using a large initial dose of SC heparin, a therapeutic anticoagulant effect can be readily achieved within 24 h, and (2) combining the results of this trial with previous studies, the efficacy of SC administered calcium appears to be comparable to IV sodium heparin. PMID- 1427458 TI - Effect of mental stress on platelet function in normal subjects and in patients with coronary artery disease. AB - We studied the effect of emotional stress (mental arithmetic for 10 min) in 10 postinfarction patients and in 10 age-matched apparently healthy subjects as controls. Blood samples for platelet function studies and for the determination of epinephrine levels in serum were taken in basal conditions, at the end of mental stress and after 30 min of recovery. Patients were studied twice, in washout of medications and after oral administration of dipyridamole, 200 mg twice a day for 6 consecutive days. Mental stress induced in patients significant increments in different hemodynamic parameters (heart rate, systolic blood pressure and diastolic blood pressure) and in serum epinephrine levels. Concomitantly, the test produced a significant increase in platelet aggregation (induced by 3 microM ADP or 1 microgram/ml collagen), the formation of circulating platelet aggregates and an increase in plasma thromboxane B2 levels. Hemodynamic parameters and platelet function tests returned to baseline values after 30 min. Similar activation of hemodynamic parameters, similar increase in epinephrine levels and lower increase in platelet function by emotional stress were observed in control subjects. Treatment of patients with dipyridamole had no effect on stress-induced increase in hemodynamic parameters and epinephrine levels, but decreased stress-related platelet activation. These data can contribute to a better understanding of the complex relationships between psychosocial factors, the hemostatic system and vascular disease. PMID- 1427459 TI - Antithrombotic effect of ticlopidine on He-Ne laser-induced thrombus formation in rat mesenteric microvessels. AB - The inhibitory effects of ticlopidine and acetylsalicylic acid (ASA) on thrombus formation in rat mesenteric microvessels were studied. The results were compared with the effect of the drugs on platelet aggregation in citrated whole blood. He Ne laser-induced thrombus formation in arterioles and in venules was significantly inhibited by 100 mg/kg ticlopidine. In contrast, a higher dose of ASA (300 mg/kg) was needed to inhibit thrombus formation and the effects of ASA were observed only in arterioles and not in venules. In addition, although the inhibition by ASA in arterioles was not strong it followed a dose-dependent manner, suggesting that the differential effect of ASA on platelets and endothelium may not be evident in vivo. Ticlopidine and ASA strongly inhibited ADP-induced whole blood platelet aggregation, but not collagen- or thrombin induced platelet aggregation. PMID- 1427460 TI - Russell's viper venom: effects on coagulating whole blood in vitro. AB - Russell's viper venom (RVV) leads to a strong activation of the coagulation system with consumptive coagulopathy and thrombopenia. For better comprehension of the pathophysiologic process, the effect of RVV was examined in an in vitro model of hemostasis. The stimulation of the coagulation system and of platelet activity can be discriminated by sequential measuring of fibrinopeptide A (FPA) generation and platelet factor 4 (PF 4) release, respectively. In coagulating whole blood both parameters show a parallel response curve in the control series (n = 6) with an initial slow phase followed by a rapid phase after 4.7 +/- 0.8 min (FPA) and 6.0 +/- 0.9 min (PF 4) of the incubation period. Varying concentrations of RVV (15, 50, 100 and 1,000 ng/ml; n = 6 each) cause a dose dependent stimulation of FPA generation as well as of PF 4 secretion. Clot formation time shows a decrease from 9 min (controls) to 6.3 +/- 2.0 min (100 ng/ml RVV) and 2.7 +/- 0.5 min (1,000 ng/ml), respectively. The concomitant addition of antithrombin III (AT III, 20 U/ml) and RVV (100 ng/ml) leads to a nearly complete normalization of hemostasis in vitro. The beginning of the rapid activation phase is comparable to that of the control group, clot formation does not occur during the 10-min incubation period. Heparin (1 IU/ml) acts as an antagonist not only of the venom-induced FPA generation, but also of the PF 4 release. Prostaglandin E1 (PGE1) (150 ng/ml) does not inhibit the RVV-stimulated FPA generation, but causes a moderate inhibition of PF 4 secretion, especially during the rapid phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427461 TI - Assessment of whole-blood spontaneous platelet aggregation during pregnancy using an impedance particle counter. AB - The slide test method of Velaskar and Chitre for determining platelet aggregation in whole blood after induction of aggregation was modified for spontaneous platelet aggregation and evaluated. The reproducibility was satisfactory (CV 1 3%). The results obtained with this method and the method of Velaskar were not significantly different. The Spearman rank correlation was 0.75 (p less than 0.0001). We established reference values for the particle counter method and Velaskar's method in pregnant and non-pregnant women; no significant change in spontaneous platelet aggregation was seen throughout pregnancy. In order to estimate the clinical value of the test in pregnancy, we followed up a number of pregnant patients with primary enhanced spontaneous whole-blood platelet aggregation before and after treatment with low-dose acetylsalicylic acid. The test was found to be suited for the detection of spontaneous whole-blood platelet aggregation and for the follow-up after treatment with acetylsalicylic acid. Further studies are necessary, however, to assess the predictive value of an aberrant test result during pregnancy. PMID- 1427462 TI - [Occupational disease No. 2101?]. PMID- 1427463 TI - [Vascular supply of the unsheathed segment of the extensor tendons of the 2d to 5th fingers of the dorsum of the hand]. AB - The dorsal approach to the metacarpal bones is through the peritendinous connective tissue of the extensor tendons. Knowledge of the vascular supply of the distal parts of these tendons, between the distal end of the tendon sheath and the tendon's osseous insertion is important, especially with respect to atraumatic technique. The course and distribution of the vessels to the extensor tendons II-V were investigated. Superficial and deep layers of connective tissue were found to contain blood vessels. The superficial vessels reach the dorsal aspect of the extensor tendon, originating from subcutaneous arteries and the large arteries of the hand. The deep vessels reach the lateropalmar aspect of the tendons and originate from the peritendinous muscular arteries. Vessel distribution suggests a direct relationship between the number of nourishing arteries and the tendon surface area. The vascular supply to the unsheathed parts of the extensor tendons shows morphological adaptations to differential mechanical stress during tendon excursion. PMID- 1427465 TI - [Traumatic aneurysm of the hand--a rare complication of a stab injury]. AB - This is a case report of a 22-year-old male who suffered a stab injury to his right hand. Sixteen days after primary wound closure, he complained of pain from a pulsating mass in his right palm, with numbness along the ulnar side of the middle finger. At operation, a false aneurysm was found and resected, after ligation of the common digital artery proximal and distal to the aneurysm. PMID- 1427464 TI - [Morbidity of the donor site of the dorsalis pedis flap]. AB - Detailed information on the dorsalis pedis flap donor-site morbidity is still lacking. In a retrospective analysis, wound-healing, cosmesis, mobility, stability, and thermographic studies of the feet were investigated. The results show a high donor-site morbidity of the dorsalis pedis flap. Indications and alternative methods are discussed. PMID- 1427466 TI - [Changes in the vascular endothelium after electro- and thermocoagulation]. AB - An experimental study was performed in animals to investigate the effect of various coagulation techniques on the vascular system. Using a microsurgical procedure, the femoral vein of fifteen rabbits was exposed bilaterally and coagulated until the lumen was closed. Electro- and thermocoagulation systems were applied. The light microscopic examination showed endothelial alterations in the course of the vessel. Analyses with the scanning electron microscope were therefore also performed. Extensive endothelial damage could be detected regularly with monopolar currents; the results were not uniform with bipolar applications. The most favorable conditions were found when thermal coagulators had been used. Damage to the parallel arteries was not detectable to a significant degree in these cases. The toxic effect of the energy applied can be morphologically divided into three stages. It should be considered whether extensive endothelial damage leads to the formation of microthrombi and thus causes clinical complications. PMID- 1427467 TI - [Current aspects of epidermal wound healing]. AB - The multilayered cornifying epithelium of mammalian skin provides a barrier protecting the organism against external damage and preventing loss from the internal milieu. The unique features of the epidermis are responsible for its regenerative capacity. Basal keratinocytes are the stem cells for a vertical differentiation pathway during which an undifferentiated keratinocyte undergoes extensive changes into a keratinized flake of the horny layer. During epithelial repair the cells change their normal pattern of differentiation. Migratory activity and proliferation are the basis for the horizontal migration of the epidermal cells, which is inhibited by cell contact and completed by differentiation and keratinization. The mechanisms of cell activation and migration are currently under intense investigation. A large number of peptide growth factors have been shown experimentally to be active in wound healing. A better understanding of the molecular basis provides new perspectives for a more specific therapy in wound healing. Keratinocyte culturing has first been used in the treatment of large burns. Modifications try to include also dermal elements. Recent developments in molecular and cell biology indicate a perspective of cultured epithelial sheets containing genetically engineered keratinocytes for epithelial gene therapy. PMID- 1427468 TI - [Long-term results of Russe modified scaphoid screw fixation II]. AB - Proximal pole scaphoid nonunion with a small necrotic proximal fragment presents therapeutical problems. Cannulated screw fixation as a modification of the Russe II procedure combines the advantages of minimal surgical exposure and trauma, preserving the blood supply of the distal fragment, and at the same time achieving rigid fixation of the autogenous bone graft. Six out of seven patients had satisfactory subjective and objective results after a mean follow-up of 12.9 years, although radiographic findings were less favorable. PMID- 1427469 TI - Bundle nailing in nonunion of the distal radius: case report. AB - A previously unreported technique for dealing with severe distal radial nonunion in the presence of marked osteoporosis and deformity in a 65-year-old female is presented. The technique involves temporary ankylosis of the wrist with bundle nails connecting the second and third metacarpal with the distal and proximal fragment of the radius, dorsal to the carpal bones and joints. Union was achieved radiographically after nine months. When the bundle nails were removed, there was some recovery of wrist movement and useful function. PMID- 1427470 TI - [Anomalous course and anomalous division of the median nerve in the distal forearm]. AB - An anatomic variation of the median nerve is demonstrated in a female patient suffering from carpal tunnel syndrome subsequent to a distal radius fracture with malalignment and reflex sympathetic dystrophy. The median nerve coursed anterior to the superficial flexor tendons from proximal ulnar toward the distal radial region of the distal forearm, giving off an ulnar branch just 2.5 cm proximal to the flexor retinaculum. This case proves that in the distal forearm, branches of the median nerve can be found both radial and ulnar to the midline. PMID- 1427471 TI - [Composite lymphoma in Sjogren's syndrome with mixed cryoglobulinemia]. AB - A 44-year-old woman with Sjogren's syndrome and mixed cryoglobulinemia developed nodal and pulmonary lymphoma 15 years after the initial diagnosis. The nodal lymphoma was of the composite type and included both monoclonal monocytoid and lymphoplasmacytoid B-cells. The extranodal pulmonary lymphoma included only lymphoplasmacytoid lymphocytes. Complete resolution of the lymphoma was achieved following 3 months of chlorambucil, 5 mg/day, and prednisone, 30 mg/day. Composite lymphoma and monocytoid lymphoma are being encountered more commonly among patients with Sjogren's syndrome. Physicians must therefore become more aware of the existence of both entities. PMID- 1427472 TI - [Kaposi's sarcoma following liver transplantation]. AB - A 54-year-old man developed Kaposi's sarcoma 2 months following orthotopic liver transplantation for hepatitis B-associated liver cirrhosis. At that time he was on combined immunosuppressive therapy (azathioprine, prednisone and cyclosporine A). The disease is very prevalent among immunosuppressed patients following renal transplantation, but is considered to be relatively rare following liver transplantation. The patient ran a relatively benign course without organ involvement and with only the skin disease. This is the first case of Kaposi's sarcoma following liver transplantation reported in Israel. PMID- 1427473 TI - [Marshmallow for investigating functional disturbances of the esophageal body]. AB - Manometric studies using water boluses do not always demonstrate disturbances in esophageal motility. We tested the use of a marshmallow bolus to induce abnormal manometric patterns in patients with dysphagia in whom manometric studies using water boluses were normal or nearly so. The study group included 12 normal volunteers and 22 patients with dysphagia and nearly normal manometric studies. Pressure was recorded along the esophageal body using 10 "wet" swallows followed by 10 "solid" swallows of marshmallow. In normal subjects there were fewer abnormal contractions after solid swallows than after wet swallows. In 15 patients solid swallows induced abnormal motility patterns which were not observed after wet swallows. The probability of inducing abnormal contractions in patients after solid swallows is significantly greater than after wet swallows (p < 0.0001). Solid swallowing is therefore useful in evaluating functional disturbances of the esophagus in patients with dysphagia. PMID- 1427474 TI - [Overdosage of glibenclamide presenting with lethargy and seizures in a child]. AB - Management of accidental overdosage with oral hypoglycemic agents in toddlers may be difficult when the history of ingestion is overlooked. We report a 21-month old girl who presented with lethargy and generalized seizures 12 hours after ingestion of an unknown number of glibenclamide pills. The blood glucose on admission was 0.5 mM/l. Symptoms resolved promptly after an intravenous bolus of glucose. Metabolic and infectious causes of hypoglycemia were ruled out. The parents denied drug ingestion initially, but further investigation revealed that she had ingested several glibenclamide pills used by her diabetic father 12 hours prior to admission. This case illustrates the problem involved in diagnosis and management of accidental drug overdosage in children when no such history is elicited and symptoms are delayed. PMID- 1427475 TI - [Management of neonatal testicular torsion]. AB - Neonatal testicular torsion is rare, and is distinguished both clinically and anatomically from torsion in the older age group. We describe 2 cases of neonatal torsion treated in different ways, which reflect the current controversy regarding the timing of surgical exploration, the need for orchiectomy, as well as the indications for contralateral orchiopexy. The distinction between prenatal and the postnatal subgroups is emphasized and a policy of treatment is proposed. PMID- 1427476 TI - [Rectosigmoid carcinoma in an adolescent girl]. AB - Carcinoma of the colon and rectum is very rare in childhood and adolescence. We describe a 16.5-year-old girl with rectal bleeding and constipation. She had been treated symptomatically for 6 months without being properly examined. Only with onset of weight loss was rectal examination performed. After workup a diagnosis of locally advanced carcinoma of the rectosigmoid with multiple lung metastases was reached. From review of the literature and our own case, it seems that the unfavorable prognosis in young patients is mainly due to lack of awareness of such a possibility, resulting in delayed diagnosis and treatment. An additional factor is the invasive nature of most colon cancers in this age group. PMID- 1427477 TI - [Development of the visual system in infants]. PMID- 1427478 TI - [Thrombocytopenia in pregnancy--implications for the mother and infant]. PMID- 1427479 TI - [What is the prosthesis of choice--biological or mechanical?]. PMID- 1427480 TI - [Sedation for outpatient dental procedures]. PMID- 1427481 TI - [Physiologic hypertrophy in athletes' heart and cardiomyopathy]. PMID- 1427482 TI - [Withdrawal of antiepileptic drugs in children]. PMID- 1427483 TI - [The problem of liver transplantation in hepatitis B virus carriers]. PMID- 1427484 TI - [Surgical treatment of Crohn's disease: an update]. PMID- 1427485 TI - [Is co-trimoxazole contraindicated in G6PD deficient patients?]. PMID- 1427486 TI - [Treatment of drug addicts--the question of criteria for success or failure]. PMID- 1427487 TI - [Seatbelt syndrome]. PMID- 1427488 TI - [Medicine, a profession in the process of development--present status and future directions]. PMID- 1427489 TI - [Current controversies in peer review]. PMID- 1427490 TI - [Gynecomastia--physiology and pathophysiology]. PMID- 1427491 TI - [An 88-year-old comatose man with right hemiparesis]. PMID- 1427492 TI - The differentiation between freshwater and marine fish trypanosomes by lectin agglutinability. AB - The agglutinability of three fish trypanosomes, Trypanosoma boissoni and T. triglae senegalensis from marine fish, and T. carassii from freshwater fish was compared. The tests were performed with trypomastigotes and epimastigotes in the exponential and stationary growth phases. The simple agglutination test, performed in microwell plates, used ten purified lectins, and revealed a clear difference between marine and freshwater strains when compared for their agglutinability with the HPA lectin. Whereas the cells of T. boissoni and T. triglae senegalensis became strongly agglutinated by this lectin, those of T. carassii remained unagglutinated in the same conditions. However, the cells of T. triglae senegalensis reacted positively with ConA lectin in the stationary phase only. The differences in structure and composition of surface polysaccharides stable after prolonged cultivation in vitro are inferred on the basis of the results obtained. PMID- 1427493 TI - Histochemistry of the racemose form of Cysticercus cellulosae. AB - The racemose form of brain cysticercosis arises from an intense proliferation of the bladder wall after the scolex part has degenerated. The proliferating zones are 2-3 times thicker than the remaining parts of the bladder and are characterized by a densely folded tegument and thick subtegumental and parenchymal layers. The tegument and subtegumental cells contain a large amount of acid mucosubstances with sulpho groups and hydrophilic lipids, and exhibit a high activity of alkaline and acid phosphatases. The parenchyma contains a large amount of glycogen. With the gradual aging of the bladder wall and with the first signs of autolysis, the enzymatic activity as well as the amounts of glycogen, neutral and acid mucosubstances, and proteins decrease, and the hydrophobic lipids prevail over the hydrophilic ones. The results obtained are important for the differential diagnostics of cestode larval stages in the human brain. PMID- 1427494 TI - Susceptibility of some species of rodents to rickettsiae. AB - The present study was designed to test the susceptibility of free-living rodents, viz Apodemus flavicollis, Microtus arvalis, Clethrionomys glareolus, Mus musculus, and outbred white mice from Dobra Voda farm, CSFR, to Coxiella burnetii, rickettsiae of the spotted fever group (Rickettsia sibirica, R. conorii, R. slovaca and R. akari) and rickettsiae of typhus group (R. typhi and R. prowazekii) by various routes of administration. The highest levels of antibodies to C. burnetii were found in A. flavicollis and M. arvalis inoculated intraperitoneally and intracerebrally. Antibodies to C. burnetii exerted peak levels between days 13 and 16 in contrast to white mice which showed maximum levels on day 28. When 10(0.5) and 10(0.05) EID50/0.25 ml of C. burnetii was administered intraperitoneally to A. flavicollis, M. arvalis and white mice, the agent was detected only in organs of wild animals. In addition to spleen, the bone marrow appeared as a predilective tissue for the detection of this agent. R. akari at a dose of 10(4.5) EID50/0.25 ml caused overt illness and death in rodents. Antibody levels to R. sibirica and R. conorii were dependent on dosage, route of inoculation and duration of infection, but were not dependent on animal species. Antibodies to R. slovaca and R. akari were dependent on dosage, infection duration and animal species but were not dependent on the route of infection. For R. conorii, R. sibirica and R. slovaca a sharp increase of antibody levels with high titres on days 4-6 and peak levels about day 11 post intraperitoneal infection was characteristic. Antibody level to R. akari increased up to day 21. Spotted fever group rickettsiae in rodents inoculated intraperitoneally were observed in various organs, particularly in tunica vaginalis and spleen at days 2-8 post infection. R. typhi at a dose of 10(4.3) EID50/0.25 ml inoculated intracerebrally or intraperitoneally killed white mice and inoculated intraperitoneally killed C. glareolus and M. musculus. The antibody response of white mice to intraperitoneal, subcutaneous or intranasal inoculation of this rickettsia was low and no antibody was detected following peroral administration. M. musculus did not develop antibodies after intracerebral, intranasal, subcutaneous or peroral inoculation of R. typhi. The target organs for this rickettsia were the spleen and tunica vaginalis. R. prowazekii inoculated intraperitoneally into white mice at a dose of 10(6.5) EID50/0.25 ml and at a dose of 10(4.5) EID50 into C. glareolus was fatal for these rodents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1427495 TI - In vitro propagation of Toxoplasma gondii in PC-1 serum-free medium. PMID- 1427496 TI - [Hemorheological effect of KB-2796, a new Ca2+ antagonist]. AB - The hemorheological effect of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4, trimethoxybenzyl)piperazine dihydrochloride, was studied in guinea pigs and rabbits in comparison with those of flunarizine (FNZ) and pentoxifylline (PXF). KB-2796 and FNZ at 10-100 microM dose-dependently prevented crenation of rabbit erythrocytes induced by the Ca2+ ionophore A23187. After incubation of guinea pig whole blood at 37 degrees C, blood micropore-filterability decreased and blood viscosity increased with the progress of erythrocyte crenation. After a 4-hr incubation, KB-2796 inhibited erythrocyte crenation and decreased blood filterability at a concentration of 30 microM, and it increased blood viscosity at 10 microM. Treatment with FNZ (30 microM) and PXF (100 microM) also inhibited erythrocyte crenation and decreased blood filterability. Intravenous administration of KB-2796 at 3 mg/kg significantly inhibited the decrease of blood micropore-filterability after occlusion of the bilateral carotid arteries in rabbits. Although FNZ (3 mg/kg, i.v.) had no effect, PXF (3 mg/kg, i.v.) produced significant inhibition. These results suggest that KB-2796 prevents increase of blood viscosity and decrease of blood filterability by inhibiting the crenation of erythrocytes and suggest that this effect may be useful for the improvement of hemorheology in ischemic disease. PMID- 1427497 TI - [Effects of a new antiarrhythmic drug, KW-3407, on canine ventricular arrhythmia models]. AB - The antiarrhythmic and direct cardiovascular effects of the new antiarrhythmic agent KW-3407, 5-[[2-(diethylamino)ethyl]amino]-7-methoxy-5,11- dihydro[1]benzoxepino[3,4-b]pyridine 1.5 fumarate, were examined. To evaluate antiarrhythmic effects, two-stage coronary ligation-, digitalis- and adrenaline induced spontaneously occurring arrhythmias were used. KW-3407, 20 mg/kg/10 min, suppressed these three arrhythmia models, similar to flecainide, mexiletine and phenytoin. The antiarrhythmic plasma concentrations, IC50, of KW-3407 for 24-hr and 48-hr coronary ligation-, digitalis- and adrenaline-induced arrhythmias were 18.1, 14.4, 18.3 and 21.4 micrograms/ml, respectively; and these values were similar to one another. In the canine blood perfused atrioventricular (AV) node, sinoatrial node and papillary muscle preparations, KW-3407 decreased the sinoatrial rate and contractile force, and increased the coronary blood flow and AV conduction times, but these effects were weaker than those of disopyramide and flecainide and were short-lived. These results indicate that KW-3407 can be expected to become a clinically useful antiarrhythmic drug. PMID- 1427498 TI - [Effects of selenium on the serum glucose and insulin levels in diabetic rats]. AB - We investigated the effects of selenium (Se) on the serum glucose and insulin levels in rats with diabetes induced by streptozotocin (STZ, 75 mg/kg, i.p.) and pancreatectomized rats. Moreover, the direct action of Se on insulin release from the isolated pancreatic islets using a slight diabetic rat was studied. The following results were obtained: 1) Selenite at a dose of 173 micrograms/kg (78.9 micrograms/kg of Se base equivalent) drastically reduced the very high level of serum glucose in acute diabetic rats within 5 to 30 min after treatment. During this time period, the insulin level in the serum showed an increasing tendency. 2) The high serum glucose level in chronic diabetic rats returned to the original level with injection of selenite for 4 days, once a day. However, Se did not elicit a significant increase in serum insulin level. 3) Although there was a tendency for the serum glucose level to decrease when selenite was administered into pancreatectomized rats, no secretion of insulin into the serum was observed. 4) Insulin release from isolated pancreatic islets was dose-dependently accelerated by the addition of selenite. These data present the new finding that Se reduced the high level of serum glucose in diabetic rats. PMID- 1427499 TI - [Effects of Kamikihi-To on autonomic imbalances in SART-stressed (repeated cold stressed) mice]. AB - The effects of Kamikihi-To (KMK), a traditional Chinese medicine, on autonomic imbalances were evaluated in SART-stressed (repeated cold-stressed) mice. These animals exhibited decreases in pain threshold and contraction of duodenum by acetylcholine, and they showed changes in their electrocardiogram and hematological parameters. All symptoms are thought to be caused by dysautonomia. KMK in dosages of 0.5 and 1.0 g/kg were administered to mice once a day for 8 consecutive days. SART stress was induced from the second day. KMK prevented the decrease in the pain threshold and contraction of the duodenum, although it had no effect on the electrocardiographic or hematological changes. KMK had no similar effect on unstressed mice. This data suggests that KMK might be useful for the treatment of clinical autonomic imbalances. PMID- 1427501 TI - Underbite and the scaling of facial dimensions in colobine monkeys. AB - This investigation was concerned with the dimensions of the facial skeleton and the incidence of underbite in colobine monkeys. Standard craniofacial dimensions and the notation of the presence or absence of underbite were recorded for skulls of 308 adult, wild-caught colobines belonging to 10 species. Underbite was noted in all species examined, ranging in frequency from 10% in Colobus polykomos to 100% in 2 species of Presbytis. Univariate statistics indicate that species with high frequencies of underbite tend to have shorter, broader maxillary dental arches, shorter faces and rostrums, and longer mandibular dental arches. A multivariate discriminant analysis supported the univariate statistics. Interspecific allometric analysis of facial measurements against a constructed size variable indicated that maxillary dimensions scale in a strongly positive manner in relation to size. However, mandibular dimensions tend to scale isometrically. This pattern of facial scaling indicates that the tendency toward underbite should increase as overall size decreases. This would explain why smaller species have higher frequencies of underbite than larger species and why females often have a higher incidence of underbite than conspecific males. Zingeser has suggested that the high incidence of underbite in colobine and some cebid monkeys is an adaptation to folivory. The results of this study support an alternative hypothesis that the high incidence of underbite in colobine monkeys is related to the pattern of facial scaling with size in combination with relaxed selection on the anterior dentition. PMID- 1427500 TI - [Overview of the progress in drug dependence studies--mainly focussing on psychic dependence]. AB - The technical term 'drug dependence' was officially adopted by WHO's Expert Committee on Addiction in 1964. Until this, to describe a state of dependence, terms such as 'poisoning', 'habit', 'ism', and 'addiction' had been used from time to time. Until the 1950's, investigators were mainly focussed on the phenomena of physical dependence. However, once the concept of psychic dependence had been introduced, behavioral and neuropharmacological studies on the modes of drug action that produce psychic dependence were activated and have progressed in the last two decades, and among the points clarified by these studies are the following: 1. The critical drug properties that produce psychic dependence are those of rewarding subjective and reinforcing effects of drugs but these effects are not the properties that produce physical dependence, although the development of physical dependence on particular drugs such as opiates may substantially enhance craving for the drugs. 2. The mesolimbic and mesocortical dopamine systems in the brain and also the N. Accumbens play a primary or at least a partial role in producing the subjective and reinforcing effects of major dependence-producing drugs such as cocaine, opiates, barbiturates, benzodiazepines, and ethanol. 3. Many drugs such as naltrexone, methadone, and some dopamine antagonists and serotonin reuptake inhibitors or antagonists were found to be effective in the pharmacotherapy of the dependence on opiates, cocaine, or ethanol. PMID- 1427502 TI - Adoption of an additional infant by a Western lowland gorilla (Gorilla gorilla gorilla). AB - A 10-year-old Western lowland gorilla, already caring for her own 14-month-old son, adopted a female neonate. The infant's mother (aged 7 years, 4 months) showed no interest in the infant, and it is unclear whether she abandoned the infant or whether it was seized by the dominant foster-mother. The foster-mother gave more maternal attention to the adoptee than to her own son but gave both infants the same protection. She adjusted her forms of transport to the age of each infant. The subadult mother of the neonate did not seek contact with her offspring during the first 4 weeks and in fact showed more interest in the 14 month-old male infant. Interactions between the two mothers were rare. The foster mother's own male infant died 2 months after she had adopted the female infant. She looked after the adopted infant for 1 year, but then lost interest so that the adoptee had to be separated. PMID- 1427503 TI - Sexual dimorphism of the pelvis in Leontopithecus (Lesson, 1840). PMID- 1427504 TI - Comparative induction of unscheduled DNA synthesis in cultured rat hepatocytes by allylbenzenes and their 1'-hydroxy metabolites. AB - The allylbenzenes estragole, methyleugenol and safrole are hepatocarcinogens in rodents at very high doses, but allylbenzene itself is neither hepatotoxic nor hepatocarcinogenic. To elucidate further the significance of metabolic 1' hydroxylation in the carcinogenicity of the allylbenzenes and to give further insights into the structure-metabolism-genotoxicity relationships of these compounds, comparative data were established on the ability of estragole, methyleugenol, safrole, allylbenzene and their 1'-hydroxy metabolites to induce unscheduled DNA synthesis (UDS) in hepatocytes derived from male Fischer 344 rats. Cytotoxicity was assessed by lactate dehydrogenase leakage. The first three compounds increased UDS in a dose-related fashion but allylbenzene was non genotoxic. 1'-Hydroxyestragole, -methyleugenol and -safrole were more potent genotoxins than their parent compounds. This difference in genotoxicity indicates the importance of the attachment of the electron-withdrawing methoxy or methylenedioxy substituents to the benzene ring. The non-linear dose-response curves for genotoxicity obtained with the allylbenzenes and their 1'-hydroxy metabolites indicate that it is important to consider dose-dependence in metabolism when interpreting the significance to humans of animal data obtained with very high doses of the compounds studied. It is likely that the use of these high doses markedly overestimates the potential hazard to humans of low doses of allylbenzenes, which generate only very small quantities of genotoxic metabolites. PMID- 1427505 TI - Lack of carcinogenicity of ferric chloride in F344 rats. AB - The carcinogenicity of ferric chloride, a compound that is used as a food additive, a haemostatic or treatment for hypochromic anaemia, was examined in F344 rats of both sexes. It was dissolved in distilled water at levels of 0, 0.25 or 0.5%, and groups of 50 male and 50 female rats were given one of these solutions ad lib. as their drinking water for up to 2 yr. The mean body weights of the treated rats were lower than control group values for both males and females. A variety of tumours developed in all groups, including the control group, but all these neoplasms were histologically similar to those known to occur spontaneously in this strain of rats, and no statistically significant increase in the incidence of any tumour was found in the treated groups of either sex. Thus it is concluded that under the conditions of this experiment, ferric chloride exerts no carcinogenic potential in F344 rats. PMID- 1427506 TI - The potential genotoxicity of sorbates: effects on cell cycle in vitro in V79 cells and somatic mutations in Drosophila. AB - Sodium sorbate, potassium sorbate and an oxidation product of sodium sorbate, 4,5 epoxy-2-hexenoic acid, were tested for their genotoxic potential in cultured V79 Chinese hamster cells and in somatic cells of Drosophila melanogaster (wing spot test, SMART). In Drosophila only the epoxide showed a weak genotoxic effect. In V79 cells, freshly prepared sodium sorbate solutions at the highest concentrations only (2.5 mg/ml, 24 hr exposure) arrested mitosis at the G2/M cell cycle phase and potassium sorbate (2.5 mg/ml) had no effect. This arrest was reversible after a 24-hr recovery interval. Sodium sorbate solutions stored for up to 208 days were cytotoxic at 2.5 mg/ml, induced cell cycle arrest in the G2/M phase and increased cellular protein content, indicating an action similar to spindle poisoning and a chemical stress reaction (adaptation processes, modification of transcription). Potassium sorbate solutions stored for 28 days were also cytotoxic. With 4,5-epoxy-2-hexenoic acid at concentrations up to 0.01 mg/ml no effects were seen. At higher concentrations (at least 0.1 mg/ml) cell killing was observed, which probably resulted from unphysiologically lowered pH in the culture medium. Overall, the results are interpreted as an indication of a weak genotoxic potential of stored sodium sorbate solutions. Thus, sorbic acid and its potassium salt at the concentrations used for food preservation can still be considered as safe for human consumption. PMID- 1427507 TI - Effect in vitro of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on the hepatic activation of dietary genotoxins by rat post-mitochondrial fractions. AB - The effect of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on the conversion of the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to its genotoxic metabolites was investigated using a modified bacterial mutation assay. The assay used Salmonella typhimurium TA98 as an indicator of the mutagenicity and hepatic post-mitochondrial fractions (S-9) from male Sprague Dawley rats as the activating system. All three fatty acids inhibited the mutagenicity of IQ without effect on the uptake of the active metabolites and/or on the DNA repair processes within the bacterial cell. The activation of three other food mutagens, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2 amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and aflatoxin B1 (AFB1) was also inhibited by these fatty acids. PMID- 1427508 TI - Effects of hickory-smoke condensate on development of pepsinogen 1-altered pyloric glands in rats. AB - Hickory-smoke condensate (HSC) is a popular food flavouring in the USA. Available data have suggested that this food additive has tumour-initiating/promoting potential. Accordingly, a commercial HSC has been investigated for its capacity to promote tumours in the rat glandular stomach using pepsinogen 1 (Pg 1)-altered pyloric glands (PAPG) as the marker of preneoplastic lesions. The development of PAPG initiated by a single intragastric administration of N-methyl-N'-nitroso-N nitrosoguanidine was significantly increased by feeding rats a diet containing 5% HSC; no effect was observed with lower doses (1.25 or 2.5%) of HSC. The results suggest that HSC has weak tumour-promoting potential in the rat glandular stomach. PMID- 1427509 TI - Relative protection given by extract of Phyllanthus emblica fruit and an equivalent amount of vitamin C against a known clastogen--caesium chloride. AB - Aqueous extracts of Phyllanthus emblica L. fruit and an equivalent amount of vitamin C were administered orally by gavage to laboratory-bred Swiss albino mice for 7 days in order to evaluate the protection afforded by the two extracts against clastogenic effects of different doses of caesium chloride (CsCl) on bone marrow cells of Mus musculus in vivo. Both pretreatments significantly reduced the frequency of chromosome aberrations induced by CsCl given at three different doses, indicating that vitamin C, an essential component of P. emblica extract, was the effective agent in protecting against the clastogenicity of the metal salt. PMID- 1427510 TI - Tissue-binding and toxicity of compounds structurally related to the herbicide dichlobenil in the mouse olfactory mucosa. AB - The herbicides dichlobenil (2,6-dichlorobenzonitrile), chlorthiamid (2,6 dichlorothiobenzamide) and their environmental degradation product 2,6 dichlorobenzamide are irreversibly bound and toxic to the olfactory mucosa following single injections in mice (Brandt et al., Toxicology and Applied Pharmacology 1990, 103, 491-501; Brittebo et al., Fundamental and Applied Toxicology 1991, 17, 92-102). In the present study, autoradiography showed an irreversible binding of radioactivity in the olfactory mucosa (preferentially in the Bowman's glands) in C57Bl/6 mice treated with the 14C-labelled analogues [14C]2,6-difluorobenzonitrile ([14C]DFBN) and [14C]2,6-difluorobenzamide ([14C]DFBA). Therefore the toxicity of DFBN, DFBA and of some structurally related compounds including benzonitrile (BN) and the herbicides bromoxynil (3,5 dibromo-4-hydroxybenzonitrile) and ioxynil (3,5-diiodo-4-hydroxybenzonitrile) in the mouse olfactory mucosa was examined. No histopathological changes in the olfactory mucosa or in the liver were observed following a single ip dose of any of these compounds [0.145 mmol/kg (all compounds); 0.58 mmol/kg (DFBN, DFBA and BN)]. Also in mice treated with the glutathione-depleting agent phorone, none of these compounds induced any histopathological changes in the olfactory mucosa. The covalent binding of [14C]DFBN in the olfactory mucosa was 16 times lower than an equimolar toxic dose of [14C]dichlobenil, suggesting a low rate of metabolic activation of DFBN in the olfactory mucosa or a low reactivity of the DFBN metabolites formed. The results of this study thus show that single doses of DFBN, DFBA, BN, IX and BX, compounds structurally related to the potent olfactory toxicant dichlobenil, do not elicit acute toxicity in the olfactory mucosa of mice. PMID- 1427511 TI - Nitroprusside intoxication: protection of alpha-ketoglutarate and thiosulphate. AB - Protection against the lethal effects of sodium nitroprusside (SNP) was observed in mice after treatment with alpha-ketoglutarate (AKG), either alone or in combination with sodium thiosulphate (STS). The LD50 of SNP was 12.0 (11.0-13.0) mg/kg in mice. Ip injection of AFG (500 mg/kg twice in 20 min) increased the LD50 1.7-fold in mice. STS (1 g/kg, ip) alone increased the LD50 5.5-fold. Furthermore, combined administration of AKG and STS increased the LD50 6.9-fold. SNP elicited increased cyanide levels in blood of mice in a dose-dependent manner. SNP (10 mg/kg, sc) administration gave rise to blood cyanide levels of 73.2 +/- 3.0 microM, 30 min after treatment. Ip injection of AKG significantly decreased blood cyanide levels by 30% in mice 30 min after treatment with 10 mg SNP/kg. A single injection of STS (1 g/kg) or a combination of AKG and STS reduced in blood cyanide levels by 88 or 98%, respectively, in mice after treatment with 10 mg SNP/kg. In addition, the increase in blood cyanide levels induced by injection of 50 mg SNP/kg was markedly inhibited by a combination of AKG and STS or (to a lesser extent) by STS alone. These results suggest that the combined administration of AKG and STS, by preventing the increase in blood cyanide levels induced by SNP, may afford protection against the toxic effects of SNP. PMID- 1427512 TI - Percutaneous absorption of nicotinic acid, phenol, benzoic acid and triclopyr butoxyethyl ester through rat and human skin in vitro: further validation of an in vitro model by comparison with in vivo data. AB - The in vitro percutaneous absorption of three model compounds, nicotinic acid, phenol and benzoic acid, and the herbicide triclopyr butoxyethyl ester (triclopyr BEE) has been investigated in flow-through diffusion cells using skin from male Fischer 344 rats and humans. After the application of the four chemicals to the epidermal surface of unoccluded full-thickness rat skin, the absorption of each compound across the skin and into the receptor fluid at 72 hr reached 3.7 +/- 0.3, 5.7 +/- 0.6, 26.7 +/- 3.7 and 48.3 +/- 1.2% (mean +/- SD, n = 2-7) of the applied dose for triclopyr BEE, nicotinic acid, phenol and benzoic acid, respectively. After the application of the four chemicals to the epidermal surface of unoccluded full-thickness human skin, the absorption of each compound across the skin and into the receptor fluid at 72 hr was significantly (P < 0.05) less than through rat skin, reaching 0.7 +/- 0.1, 0.7 +/- 0.2, 18.8 +/- 1.3 and 37.8 +/- 6.9% (mean +/- SD, n = 2-7) of the applied dose for triclopyr BEE, nicotinic acid, phenol and benzoic acid, respectively. Occlusion of the skin surface with teflon caps often significantly (P < 0.05) enhanced the percutaneous absorption of the model compounds, although this effect was not uniform, varying with the compound under study and the skin (rat or human) used. When rat skin was occluded with teflon caps, the extent of absorption at 72 hr reached 8.6 +/- 0.8, 36.2 +/- 1.7 and 51.8 +/- 3.3% (mean +/- SD, n = 3-4) for nicotinic acid, phenol and benzoic acid, respectively. Corresponding values for human skin occluded with teflon caps were 3.3 +/- 1.6, 47.1 +/- 0.5 and 65.5 +/- 7.1% (mean +/- SD, n = 3 4). The experiments on the absorption of each model compound through rat and human skin were repeated and there was generally good agreement between the results from the two sets of experiments. The in vitro data reported compare favourably with data obtained by other workers using both in vitro and in vivo methodologies. The in vitro: in vivo correlation supports the use of the flow through diffusion cell system as a model for the prediction of percutaneous absorption in vivo in the rat and in humans. PMID- 1427513 TI - Effects of the colour additive caramel colour III on the immune system: a study with human volunteers. AB - Administration of the colour additive Caramel Colour III to rats has been associated with decreased numbers of lymphocytes and several other changes in the immune system, as well as in immune function parameters, specifically in animals fed a diet with a relatively low vitamin B6 content. The effects are caused by the imidazole derivative 2-acetyl-4(5)-tetrahydroxybutylimidazole (THI). Caramel Colour III is commonly used in food products such as bakery products, soya-bean sauces, brown sauces, gravies, soup aromas, brown (dehydrated) soups, brown malt caramel blend for various applications, vinegars and beers, and effects in humans on dietary intake cannot be excluded. Elderly male volunteers with a marginal deficit in vitamin B6 were considered a relevant and potentially sensitive group to study possible effects of Caramel Colour III on blood lymphocyte numbers (total and within subsets) or on proliferative responses of lymphocytes to mitogenic stimulation. In addition, several other haematological parameters, as well as serum immunoglobulin levels and immunoglobulin production in vitro by pokeweed mitogen-stimulated mononuclear blood cells were studied. The results of this double-blind intervention study demonstrated that in a selected test group of apparently healthy elderly male volunteers with a biochemically marginally deficient vitamin B6 status, Caramel Colour III containing 23 (commercial sample) or 143 (research sample) ppm THI and administered at the level of the current acceptable daily intake of 200 mg/kg body weight/day for 7 days did not affect any of the factors investigated. PMID- 1427514 TI - Studies on endogenous formation of N-nitroso compounds in the guinea pig supplemented with proline or thioproline and sodium nitrate. AB - The endogenous formation of N-nitrosoproline (NPRO) and N-nitrosothioproline (NTPRO, N-nitrosothiazolidine-4-carboxylic acid) was studied by monitoring their excretion in the urine of guinea pigs given oral doses of 10 mg proline or thioproline after supplementation with 34 mg (0.4 mmol) sodium nitrate. In order to estimate the conversion of nitrate to nitrite, the animals were also supplemented with 3.5 mg (0.05 mmol) sodium nitrite instead of sodium nitrate. In animals fed commercial diets, the excretion of NPRO and NTPRO under supplementation with sodium nitrate was 2.0 micrograms and 28.7 micrograms/animal/day, respectively, whereas the excretion under supplementation with sodium nitrite was 0.7 micrograms and 13.3 micrograms/animal/day, respectively. The higher excretion of NTPRO than NPRO in each case shows that thioproline is more effective for nitrite trapping than proline. The animals supplemented with nitrate excreted more than twice the amounts of NPRO or NTPRO than those supplemented with nitrite. It is assumed, therefore, that more than 0.1 mmol nitrate is reduced to nitrite and takes part in the endogenous nitrosation of the guinea pig. When various concentrations of L-ascorbic acid (AsA), known to inhibit the formation of N-nitroso compounds, were also administered orally to animals immediately after supplementation with sodium nitrate, the NPRO excretion decreased with increasing AsA concentration. These data indicate that the guinea pig, which is unable to synthesize AsA as well as humans, may be an appropriate animal model for evaluation of the endogenous nitrosation ability of humans ingesting nitrate. PMID- 1427515 TI - Effects of phenolic smoke condensates and their components on hepatic drug metabolizing systems. AB - Treatment of food with wood smoke is a long-established method of preservation and flavouring food. Recently, hardwood smoke condensates, purified of polycyclic hydrocarbons, have become of importance for direct flavouring of sausage-meat. The acute toxicity of the purified phenolic fraction in mice after intraperitoneal administration was therefore investigated. The LD50 was found to be 940 mg/kg body weight, which is about three times the LD50 of phenol (about 300 mg/kg). Only high concentrations of phenols or smoke condensate fractions are able to damage cytochrome P-450 by conversion to cytochrome P-420, whereas lower concentrations exhibit inhibitory effects on monooxygenase activity. Inductive properties of the phenolic fractions could not be demonstrated. Concentrations in vivo of free phenolic compounds do not reach inhibitory levels, since the hexobarbital-induced sleeping-time and 14CO2-exhalation after administration of p [methoxy-14C] acetanilide are not altered. It is concluded that the phenolic compound intake with food regularly treated with smoke condensate fractions is below a toxicologically relevant level. PMID- 1427516 TI - A 4-week feeding study of ground red chilli (Capsicum annuum) in male B6C3F1 mice. AB - The toxicity of red chilli was examined in male B6C3F1 mice fed a commercial meal diet mixed with ground Capsicum annuum (Linn.) at levels of 0.5, 1.0, 2.5, 5.0, 7.5 and 10% by weight. Mice were offered control or test diets ad lib. starting at 6 wk of age. Food consumption was measured daily and individual body weights recorded weekly for the 4-wk feeding period. General health, body weight and food intake were apparently not adversely affected at any level of pepper consumption. Histopathological evaluation revealed slight glycogen depletion and anisocytosis of hepatocytes in the 10% group. However, other organs did not reveal any lesions attributable to the chilli exposure. It appears that red chilli is relatively non toxic at the doses tested in male B6C3F1 mice. PMID- 1427517 TI - A novel pharmacological approach for paraquat poisoning in rat and A549 cell line using ambroxol, a lung surfactant synthesis inducer. AB - Paraquat (PQ) is a widely used herbicide that causes acute adult respiratory distress syndrome (ARDS) and chronic lung damage (diffuse fibrosis). One of the earliest biochemical effects induced by PQ is damage to type II pneumocytes with consequent depletion of surfactant. With the aim of counteracting the toxic effects of PQ, a series of investigations were performed into the possible protective effect of the drug ambroxol, which induces the synthesis of surfactant in lung alveolar type II cells. The number of survivors and survival time of rats treated ip with 35 mg PQ/kg was significantly increased by 3 days of ambroxol pretreatment and by ambroxol treatment 30 min or 2 hr after PQ. Total phospholipid content in lung and bronchoalveolar lavage fluid (BALF) was significantly reduced 30 hr after treatment with PQ alone. The association of ambroxol with PQ significantly antagonized this reduction. In BALF the ratio between palmitic acid and stearic acid concentrations was significantly lower in animals treated with PQ alone but was returned to normal by the association with ambroxol. The cell line A549, exposed in vitro to PQ concentrations from 0.5 x 10(-4) to 2 x 10(-3) M, showed a significant dose-dependent loss of viability. Cells pretreated with ambroxol (10 mg/ml) were more resistant to PQ and their viability started to decrease significantly only from a PQ concentration of 0.8 x 10(-3) M. Membrane microviscosity was measured on the same cells. Cells treated with PQ alone showed a reduction of membrane microviscosity, which was significantly counteracted by ambroxol pretreatment. The curves of modification of membrane microviscosity of cells treated with PQ and with ambroxol plus PQ paralleled those of cell viability, indicating that the stimulation of surfactant synthesis in vitro may be a prerequisite for counteracting some of the early effects of PQ. PMID- 1427518 TI - Comparison of the partition coefficient and skin penetration of a marine algal toxin (lyngbyatoxin A). AB - Lyngbyatoxin A is produced by marine algae, and causes local cutaneous toxicity in swimmers. The purpose of this research was (1) to determine the partition coefficient of lyngbyatoxin A in octanol/water and (2) to use methods in vitro to measure the penetration and distribution of lyngbyatoxin A in guinea pig and human skin. Discs of excised guinea pig and human skin were mounted in diffusion chambers that exposed the epidermal surface to air and bathed the dermis with HEPES-buffered Hanks' balanced salt solution with gentamicin sulphate. The epidermal surfaces were dosed with 26 micrograms lyngbyatoxin A/cm2 dissolved in 13 microliters dimethyl sulphoxide/cm2. The diffusion chambers were incubated at 36 degrees C for varying periods (1.0-24 hr). HPLC was used to quantify lyngbyatoxin A. Skin penetration was calculated by summing the amount of lyngbyatoxin A recovered from the dermis and receptor fluid. The mean partition coefficient for lyngbyatoxin A was 1.53. Penetration of lyngbyatoxin A (expressed as a percentage of dose, n = 3) in guinea pig and human skin was 23 and 6.2 (respectively) after 1 hr of topical exposure. The amount of lyngbyatoxin A in the dermis and receptor fluid did not change significantly over time. PMID- 1427519 TI - Embryotoxicity study of propenoic acid, 3-(4-methoxyphenyl)-3-methylbutylester in the Wistar rat. AB - 3-(4-methoxyphenyl)-3-methylbutylester, propenoic acid (MPMBE; CAS no. 71617-10 2), a UVB-light filter used for sun protection of the skin, was administered once daily by intragastric gavage to pregnant Wistar rats on days 6-15 of gestation. Doses of 0.25 ml/kg/day (study group: D0.25), 0.75 ml/kg/day (D0.75) and 2.25 ml MPMBE/kg/day (D2.25) were applied. A positive control group (Pos) received 15 mg (all trans) retinoic acid/kg/day. MPMBE revealed some toxic effects in the dams of the group receiving the highest dose (D2.25): marked loss of body weight, polydipsia, reduced food consumption and intensified loss and thinning of hair. Only thinning or partial loss of hair without any other harmful effects was seen in the dams of group D0.75. An increase in embryonic deaths was striking in group D2.25; the living foetuses revealed signs of retarded development, but no major external or internal anomalies as signs of teratogenicity. This study was not able to present any teratogenic effects induced by MPMBE in the offspring, even at very high oral doses (> 2 g/kg/day) that caused substantial toxicity in the dams. In conclusion, concerning embryotoxicity an oral dose of 250 mg/kg/day MPMBE is regarded as a safe no-observed-effect level, whereas even 750 mg/kg/day MPMBE--following acknowledged rules--can be judged as a borderline no-observed adverse-effect level. PMID- 1427520 TI - Guidelines for safety evaluation of cosmetics ingredients in the EC countries. AB - The Scientific Committee on Cosmetology (SCC) of the Commission of the European Communities was established in 1978 to assist the Commission in the application of the 76/768 Directive, which regulates the production and marketing of cosmetics products. The Committee has been asked to update the general guidelines, defined in 1982, for testing cosmetics ingredients with the aim of ensuring consumers' safety. In the present paper the full document approved by the SCC in October 1990 is reported. This new document is based on the experience of the Committee over the last 10 years, during which more than 400 cosmetics ingredients have been evaluated. The document also highlights the need to proceed to define standard methods to be used to assess dermal absorption and phototoxicity--areas in which international guidelines have not yet been approved. The document also includes some comments made by the author in order to explain better the position of the Committee in relation to certain items. PMID- 1427521 TI - Methyl isothiocyanate in wine. PMID- 1427523 TI - Food emulsifiers and stabilizers. PMID- 1427522 TI - Carcinogens--classification, ranking and handling. PMID- 1427524 TI - Foods for infants and young children. PMID- 1427525 TI - Great toe metatarsophalangeal joint arthrodesis: a user-friendly technique. AB - Thirty-four feet (23 patients) were treated with a metatarsophalangeal (MP) joint fusion of the hallux using five threaded 0.062-in K wires for fixation. Operations were done for the following diagnoses: rheumatoid arthritis (26 procedures), hallux rigidus (1), salvage of previous bunionectomies (3), hallux valgus with absent toe, bilateral fusion (2), severe hallux valgus with chronic MP joint synovitis (1), and congenital hallux varus (1). The ages ranged from 17 to 73 years, with an average of 55 years. Follow-up was available on 31 of the fusions by questionnaire and telephone contact, with an average follow-up of 24 months and a minimum of 1 year. The successful arthrodesis rate was 97%. In 9% of the procedures (three cases), the patients were dissatisfied: This was due to pain under the first metatarsal head in two cases and to impingement between the first and second toes in a third case. In 91% of the fusions (29 of 32 patient responses), the patients stated that they would have the surgery if they had to choose again. Patients indicated "complete satisfaction" in 15 fusions and "satisfaction with reservations" in 14. Patients felt that their ability to wear desired shoes was improved in 48% of the procedures, was unchanged by the fusions in 26%, and was worse than before the operation in 26%. Based on this study and review of the literature, a recommendation is made for fusing the rheumatoid hallux with 25 degrees to 30 degrees of valgus and 10 degrees of extension. In general, selection of toe position for fusion is based on reducing stress on the hallux interphalangeal joint and accommodating the position of the second toe. The multiple pin fixation technique gives a high incidence of fusion, it is easy to perform, and it is adaptable to the varying requirements for toe position. PMID- 1427526 TI - Chevron osteotomy for hallux valgus. AB - A retrospective study of the Chevron osteotomy procedure for hallux valgus was carried out on 112 patients (168 feet) with an average age of 39.7 years (range 19 to 61 years). The average follow-up was 4.4 years (range 13 months to 7.5 years). The preoperative diagnosis was symptomatic hallux valgus. The average preoperative intermetatarsal 1-2 angle was 15.5 degrees (range 11 degrees to 18 degrees) and the hallux valgus angle was 28.1 degrees (range 21 degrees to 42 degrees). The operation was effective in improving symptoms, cosmesis, and function and in decreasing the deformity. PMID- 1427527 TI - Ankle arthroscopy: review and long-term results. AB - Ankle arthroscopy has evolved over the past decade as a diagnostic and an operative modality. Forty ankle arthroscopies were performed by the senior author (G.J.S.) for osteochondral fractures, chronic sprains unresponsive to conservative treatment, posttraumatic osteoarthritis, adhesions, locking, instability, synovitis, and ankle disability of undetermined cause. Thirty cases with at least 24 months of follow-up were reviewed. Complications occurred in two patients: reflex sympathetic dystrophy and a fibular fracture. Postoperatively, the patients were rated clinically as having 13% excellent, 60% good, 17% fair, and 10% poor results. However, 95% of the patients stated that they would undergo the same operation again if needed. Results were significantly better in those patients who had chondral or osteochondral defects as the diagnosis, and in noncompensation cases. PMID- 1427528 TI - The use of ultrasonography in the foot and ankle. AB - Ultrasonography of the soft tissue has achieved an increasing importance in the last years. Since sonography of the shoulder, knee, muscles, and tendons has become a routine method, there is less application of ultrasound in foot and ankle pathology. Since 1985, ultrasonography has been the routine examination technique in the Trauma Department of Hannover Medical School, Hannover, Germany. We now have a series of more than 4000 sonographic examinations. This paper gives a comprehensive overview of the possibilities in application and technique of ultrasonography in foot and ankle disorders. The sonographic patterns of the pathological changes of the main structures are described. PMID- 1427529 TI - Collateral ligament reconstruction of the unstable metatarsophalangeal joint: an in vitro study. AB - Anatomic reconstruction of the collateral ligaments of the lesser metatarsophalangeal joints is proposed for certain cases of metatarsophalangeal instability. The suggested reconstruction involves replication of the attachments of the collateral ligaments. As an example of such a reconstruction, the interosseous tendon was used in this study as a graft for anatomic replacement of the collateral ligaments. The tendon was left attached distally where its attachments include the volar plate and proximal phalanx, thereby resembling the distal attachment of the collateral ligament. The proximal portion of the tendon was inserted into the metatarsal head, replicating the attachment of the collateral ligament at that location. Preliminary testing of such a reconstruction shows that it can re-establish stability caused by loss of the collateral ligaments. Such a procedure may be applicable in select cases of crossover toe deformity and straight vertical instability. PMID- 1427530 TI - The morbid anatomy of congenital deficiency of the tibia and its relevance to treatment. AB - Two specimens obtained from a 5-month-old boy with bilateral type 1a congenital tibial deficiency were dissected to describe their morbid anatomy. Examination revealed a rigid equinovarus deformity, absence of a tibial remnant, an abnormal saddle-shaped talus, and several tarsal coalitions. Observation of the arterial pattern during surgery supported the previously reported finding that persistence of an immature arterial structure is inherent in this condition. Knowledge of potential structural anomalies is essential during the planning of an amputation or of a knee or an ankle reconstruction. Anatomic abnormalities may affect the design of soft-tissue flaps in an amputation and plantigrade positioning and foot biomechanics in reconstructive procedures. PMID- 1427531 TI - Radiological assessment of a modified anterior drawer test of the ankle. AB - Chronic ankle instability is a common complication of ankle sprain. The clinical assessment of ankle instability is usually incomplete and difficult to interpret. Recently, more attention has been paid to the value of the anterior drawer test of the ankle. We assessed the accuracy of a modification of the anterior drawer test, comparing it with radiological stress view of the ankle in 25 patients with recurrent ankle sprain. The radiological examinations were performed by a TELOS instrument and included lateral and anteroposterior stress views. We found that the modified anterior drawer test correlated with the posterior opening of the tibiotalar joint and with the lateral tilt of the talus. We conclude that a slightly positive modified anterior drawer test may indicate injury to the anterior talofibular ligament. A significant movement of the ankle elicited by the modified anterior drawer test may indicate combined injury to anterior talofibular and calcaneofibular ligaments. PMID- 1427532 TI - Ankle fracture classification systems: a case for integration of the Lauge-Hansen and AO-Danis-Weber schemes. AB - The two dominant classification systems for ankle fractures in use are the Lauge Hansen and AO-Danis-Weber schemes. Each has certain advantages and disadvantages. Because of basic similarities, integration of these systems into one scheme involving three basic patterns with appropriate staging appears to be reasonable. This integration is based upon combining the pronation-abduction and pronation external rotation injuries in Lauge-Hansen's scheme into one pronation-abduction external rotation pattern. The resultant system would appear attractive in terms of combining relative simplicity with completeness. PMID- 1427533 TI - Triple arthrodesis through a single lateral approach: a cadaveric experiment. AB - Using a single lateral approach, triple arthrodesis was performed on six cadaveric feet. An attempt was made to obliterate the talocalcaneal, talonavicular, and calcaneocuboid joints. The limbs were subsequently disarticulated to allow for an inspection of the talonavicular, talocalcaneal, and calcaneocuboid joints. An estimate of cartilage and subchondral bone removed from each articular surface was made by a single observer (J.V.B.) by direct visual inspection. Results were as follows: calcaneocuboid joint, 90% of cartilage removed; talocalcaneal joint, 80% of cartilage removed; talonavicular joint, 38% of cartilage removed. Failures at the talonavicular joint were attributed to a poor appreciation of the anatomy of the talar head and poor observation. Complications involved in obliteration of the talonavicular joint from a single lateral approach included: inadvertent division of the talar neck; inadvertent division of the talar head; removal of excessive bone stock; medial skin punctures; and creation of an iatrogenic cut through the talar dome. Therefore, a triple arthrodesis through a single lateral approach, as described by Ryerson, Hoke, and Campbell, cannot be recommended. The talonavicular joint should be approached through an auxiliary medial incision, as recommended by Cracchiolo. This paper documents the experience of a beginner with this operation, and demonstrates the value of using the anatomy laboratory. PMID- 1427534 TI - The dynamics of peroneus brevis tendon splits: a proposed mechanism, technique of diagnosis, and classification of injury. AB - The etiology of peroneus brevis splits is unclear. Because longitudinal splits in the peroneus brevis tendon do not necessarily effect the integrity or strength of the tendon, it is difficult to ascertain whether or not injury to the peroneus brevis tendon is present. Recent clinical, anatomic, and histologic reports have suggested that the split develops from prolonged mechanical attrition within the fibular groove as a result of ankle trauma with resultant lateral ankle instability and incompetency of the superior peroneal retinaculum with resultant subluxation of the peroneal tendons. This cascade of events may result in splitting of the peroneus brevis tendon. The purpose of this paper was to report the investigation of the mechanism by which peroneus brevis splits develop, to describe a technique of diagnosis, and to propose a classification of injury. Peroneus brevis splits are the result of a dynamic mechanical insult at the fibular groove. Laxity of the superior peroneal retinaculum combined with peroneus longus mechanical compression causes the peroneus brevis to splay out and eventually split over the sharp posterior edge of the fibula. Anatomic factors, such as a shallow fibular groove (congenital convex groove) or the presence of an anomalous low-lying peroneus brevis muscle belly or peroneus quartus tendon, may also play a role in this mechanism by interfering with the competence of the superior peroneal retinaculum. PMID- 1427535 TI - Traumatic subluxation/dislocation of the peroneal tendons. AB - Traumatic subluxation/dislocation of the peroneal tendons has been reported following a variety of sports-related activities. The peroneal musculature contracts reflexively during the injury and overcomes the restraining soft tissue. The tendons can then dislocate anteriorly from behind the distal fibula. Some patients have anatomical variations of the posterolateral ankle that predispose them to injury. If the physician is unaware of the injury, the diagnosis may be missed in the acute setting and can develop into a chronic, disabling condition. Treatment of the acute injury is controversial because advocates exist for both conservative and surgical therapies. The chronic, painful lesion should be treated operatively. A tremendous number of surgical procedures have been described for the treatment of chronic tendon dislocations. Choice of a surgical procedure depends upon the anatomy of the peroneal groove and the retinaculum, and the nature of the damage to the area. PMID- 1427536 TI - [The spiral CT imaging technic--the initial experience for orthodontic examinations]. AB - Within the course of the rapid development of CT technology, a new imaging technique, spiral computed tomography, is presently undergoing clinical testing. This procedure is based on a complete investigation of large volumes. In order to determine the suitability of this technique for the diagnostic evaluation of orthodontic problems, 25 patients were investigated. The most important advantage of this volumetric CT technique proved to be the capability of permitting complete recording of the object with only one scan, the extremely short examination time, and the associated reduction in radiation exposure, coupled with mostly improved image quality. These advantages, together with a discussion of various recording parameters and possible applications, are illustrated on the basis of typical cases. For orthodontic problems, the recording of small volumes provides the best three-dimensional surface reconstruction available at present. PMID- 1427537 TI - [The initial morphological state in the basally pneumatized maxillary sinus--a radiological-histological study in man]. AB - Twenty human autopsy specimens of the lateral maxilla with radiologically diagnosed extended basal maxillary sinus were prepared either in the horizontal, sagittal or transversal plane. Generally the cortical bone of the maxillary sinus showed a thickness up to 1000 microns. In areas with root contact histological findings could be described as follow: reduction of thickness, bone perforations, bone perforations combined with apical and or lateral root resorptions and root resorptions without bone perforations. These morphological findings could not be verified by X-ray examination. PMID- 1427538 TI - [The testing of the toxicity of the plastics used in orthodontics]. AB - Eighteen bracket adhesives and one to three differently coloured samples of the plastic materials Orthocryl and Wil-o-dont used for removable appliances were tested for toxicity in vitro by cell culture using both L-929 mouse fibroblasts and human keratinocytes. The results differed from product to product. Some adhesives were moderately and some slightly toxic, while others were non-toxic. After 30 days of washing in PBS, none of the adhesives showed any toxicity. Orthocryl was not toxic regardless of colour, while the possible toxicity of Wil o-dont could be a problem. PMID- 1427539 TI - [The deactivation behavior and effectiveness of different orthodontic leveling arches--a dynamic analysis of the force systems]. AB - Using the orthodontic measuring and simulation system (OMSS), the deactivation behaviour of diverse orthodontic levelling arches was investigated. The vertical forces and uprighting moments, as also the levelling effectiveness for initial malalignments of tooth 21 (1 mm and 2 mm infraocclusion, 20 degrees angulation) were measured, with the influence of various ligatures used in clinical practice being taken into account. The results may be summarized as follows: In the case of a large vertical offset (infraocclusion) the vertical forces can attain values of up to 3.8 N, depending on the type of levelling arch used. On deactivation, we can observe a sharp decrease in force caused by the frictional resistance between bracket and arch wire, which has to be overcome by the wire. The loss of desired force caused by friction may be as much as 50%, and is determined by the arch wire, bracket and mode of ligation. A smaller vertical offset (infraocclusion) (1 mm) is associated with extrusive forces of 0.2 N--0.8 N. Using looped levelling arches made of 0.016" standard steel wire, there is no frictional loss of orthodontic force, so that the highest vertical forces (more than 3.0 N) are observed with these arch wires. With an initial angulation of the tooth of about 20 degrees, uprighting moments of between 3.0 Nmm and 33.0 Nmm are measured, the looped arches again generating the highest moments. To ensure adequate uprighting moments in a combination of vertical offset (infraocclusion) and angulation, very high extrusive forces must be accepted. As a dynamic analysis of the tooth movement with the OMSS shows, the use of a specific arch wire results in a typical levelling defect. There is no general correlation between extrusive force or uprighting moment and the levelling effectiveness of an orthodontic arch. It is not possible to recommend a particular levelling arch. PMID- 1427540 TI - [A pseudoelastic NiTi uprighting spring for the molars--its design, biomechanical testing and clinical use]. AB - Uprighting inclined molars is one of the most common problems encountered in pre restorative orthodontics. To prevent occlusal trauma, an intrusive force has to be applied to the molar in addition to the uprighting moment. Owing to their construction, current mechanical devices for uprighting either to not meet this requirement, or are difficult to adjust when in place. For this reason, an improved uprighting spring is described which utilizes the properties specific to super-elastic (pseudo-elastic) NiTi alloys. The most important property of super elastic wires is the fact that they produce constant forces or moments within a specific deformation range. In order to utilize this useful property, certain design criteria have to be met. Recent measurements have shown that a super elastic wire (Sentalloy, 0.016'' x 0.022'') having a length of 10 mm generates a constant moment of 7 to 8 Nmm within a bending angle of 50 degrees to 180 degrees. On the basis of these results, a table that permits the determination of the proper wire length needed to provide a constant moment within a given range of bending angles is proposed. The superelastic uprighting spring described here comprises an NiTi wire segment having a length of 7 mm and a mesial and distal steel wire segment. In the active state, the spring generates an uprighting moment of 8 Nmm and an intrusive force of 0.6 N. Numerical analysis using the finite element program, SOLF/MESY, and biomechanical testing with the orthodontic measuring and simulation system (OMSS) have shown that this force system remains stable throughout the entire uprighting process. The clinical application of the spring is demonstrated in a specific case. PMID- 1427541 TI - [The tensile strength of bracket adhesives depending on the adhesive layer thickness--an in-vitro study]. AB - The purpose of this study was to determine the influence of the thickness of the adhesive layer between bracket base and enamel surface on tensile bond strength. Stainless steel brackets with retentive net bases were bonded to bovine incisors with adhesive layers varying in thickness from a minimum of 0.0 mm to a maximum of 0.8 mm. Eight different orthodontic adhesives were investigated; in order to simulate the procedure of indirect bonding, combinations of two different adhesives were also tested. It was found that the highly filled composites provided greatest bond strength. Increasing the thickness of the adhesive layer had no significant influence on tensile bond strength. In the case of light-cured composites, maximum tensile bond strength was achieved at a thickness of the adhesive layer of 0.2 mm. This is probably due to better penetration of light at this thickness. In the case of chemically curing no-mix adhesives, it was impossible to produce effective adhesive layers thicker than 0.2 mm, presumably because curing at the primer paste interface becomes a problem at greater thickness. The influence of cement thickness on tensile bond strength was basically identical whether brackets were bonded with one or two adhesives. Thus, an additional adhesive-adhesive interface has no influence on bond strength. If adhesive layer thickness of more than 0.2 mm are required, a chemically cured, highly filled paste-paste system should be used. PMID- 1427542 TI - [The correction of fanned-out incisors--an important orthodontic contribution to aesthetic dentistry]. AB - Account has to be taken of the increased aesthetic awareness of the adult patient by all sub-specialties of dentistry. Here, orthodontics often plays the role of a central link between periodontics and prosthetics. Taking pathological migration of the incisors as an example, the pathogenesis, therapeutic procedures and orthodontic possibilities for the restoration of normal dentofacial aesthetics are demonstrated and discussed. PMID- 1427543 TI - [Ventricular function in hypertrophic cardiomyopathy. Systolic and diastolic ventricular function]. AB - BASIC CONSIDERATION: Hypertrophic cardiomyopathy is defined as a primary myocardial disease associated with a hypertrophic non-dilated left ventricle with no other heart or systemic disease that might lead to hypertrophy of the left ventricle. The leading symptoms are effort-associated angina and dyspnea, rapid fatigue, dizziness and syncope. MAIN POINTS DISCUSSED: The hemodynamic situation is characterized by a hyperdynamic systole and impaired diastole and left ventricular filling. In the obstructive form, hypertrophy of the basal septum and an anteriorly moving mitral valve during systole result in an end-systolic reduction in the cross-section of the outflow tract associated with considerable intraventricular pressure gradients. Disturbances in the myocardial calcium metabolism are presently suspected to be causally involved in the diastolic function impairment. PMID- 1427544 TI - [Hypertrophic obstructive cardiomyopathy: surgical therapy]. AB - Surgical treatment of hypertrophic obstructive cardiomyopathy (HOCM), which may present in a typical (subaortic) or atypical (mid-ventricular) form, is indicated only after prior long-term drug treatment. The results obtained in 353 patients presenting with a symptomatic form of HOCM operated on between 1963 and 30 June 1991 are reported. The operative procedure took the form of transaortic subvalvular myectomy (TSM) as described by Morrow, modified by extending the myectomy. The patients comprised 210 males and 143 females aged between 6 and 76 years (average age 41.7 years). With few exceptions, all patients were in clinical stage III or IV (NYHA). The overall hospital mortality rate was 4.8% (n = 17); for TSM alone 3.1% (n = 8 out of 261 patients), for combination surgery with additional surgical measures 9.8% (n = 9 out of 92 patients). Among the last 194 patients (since 1984), the mortality rate was 2.06% (n = 4). To date, follow up show an improvement in the symptoms and physical performance, and an annual mortality rate of about 1.8-4% among patients treated with drugs, and a post operative mortality of about 1.1%, so that in HOCM patients with symptoms despite prior drug treatment, surgery can be recommended. PMID- 1427545 TI - [Dangerous hyponatremia. Part 2: Therapy of hypotonic dehydration and hyperhydration]. PMID- 1427546 TI - [Treatment of reactive depression with sulpiride. Double-blind study with sulpiride and amitriptyline in an interindividual comparison]. PMID- 1427547 TI - [The tissue effect of an antibiotic is decisive. Respiratory tract infections- intracellular pathogens]. PMID- 1427548 TI - [Adult children of alcoholics. A new diagnostic group with reference to general practice and clinical aspects]. AB - FUNDAMENTAL CONSIDERATIONS: Adult children of alcoholics have, in recent years, become identified as a specific group with often characteristic patterns of health disorders. MAJOR POINTS: Those involved have a three- to four-fold greater risk of developing a dependence themselves than the general population. They are more likely to marry partners who are also dependent and have an above-average propensity toward separation and divorce. Most members of this group have adopted a specific role within the family they come from: for example that of the whipping boy, family hero or fool. Of therapeutic importance is the recognition of one's own involvement through parent dependence and to develop an awareness of specific areas of disorder, for example, in a partnership, self-identity crises, emotional blockades and the risk of becoming dependent oneself. CONCLUSIONS: Therapists with experience of habit-forming disorders and social family work can develop specific activities within the general practice, psychosocial counseling centers, and even in detoxication services. The new self-help groups of adult children of alcoholics are very helpful. PMID- 1427549 TI - [Amaurosis fugax]. AB - OBJECTIVE: Presentation of the etiology, diagnosis, possible complications and treatment of amaurosis fugax. DEFINITION: amaurosis fugax is a transient monocular loss of vision, usually affecting the entire visual field. MAJOR POINTS: Amaurosis fugax is caused by transient retinal ischemia resulting from embolism, hemodynamic insufficiency or ocular vascular disease. In view of the high complication rate (annual blindness rate 1%, annual risk of an ischemic insult 2%, myocardial infarction 30%, and an 18% mortality rate), an immediate search for the underlying causes is mandatory. Diagnostic evaluation should include ophthalmological, neurological and cardiovascular investigations. Management of amaurosis fugax comprises, in the first instance, treatment of the underlying disease and administration of anti-platelet agents. In cases in which stenosis of extracranial vessels presents, endarterectomy may sometimes be considered. PMID- 1427550 TI - [Echocardiography findings in hypertrophic cardiomyopathies. Diagnostic value of different echocardiography procedures]. AB - In the present paper, the contribution of TM 2D and Doppler echocardiography to the non-invasive diagnostic evaluation of hypertrophic cardiomyopathies is discussed. The selective use of various echocardiographic possibilities for the representation (visualization) of typical morphological and functional changes in hypertrophic myocardial diseases is described. PMID- 1427551 TI - [Treatment of orofacial infections. Taurolidine--an alternative treatment concept to antimicrobial chemotherapy]. PMID- 1427552 TI - [Combitube--a new instrument for emergency intubation]. PMID- 1427553 TI - [Physical therapy and speech therapy in Parkinson syndrome--a status assessment]. AB - 74 inpatients and outpatients (mean age 71.9 years) with idiopathic Parkinson's disease, a vascular pseudo-parkinsonian syndrome or a Parkinson-associated dementia were analysed by present-state clinical rating with regard to use and needs of physical and speech therapy. 55% of the patients had physical therapy whatsoever, 32% of them on a daily schedule. 58% of patients without everyday physical therapy indicated to do less physical therapy than one year ago or that they have quite any exercise. This item showed significant correlations with: age of disease onset over 70 years, Hoehn-Yahr stage of 3 and over, activities of daily living according to Schwab-England of less than 60%, diagnosis of vascular pseudoparkinsonian syndrome or Parkinson-associated dementia, more frequent use of community support services for the ambulatory elderly. Only 8% of the patients had ever had speech therapy. Using both ratings of complaints and clinical findings, about 30% of patients had moderate to severe impairment of speech, 80% of these had also considerable memory disturbances. The study suggests that the need for physical therapy might be derived more from patient's assessment of reduced daytime motor activities than from a scaled item rating of an external observer. Use and continuity of physical and speech therapy in Parkinsonism seems to be limited largely by cognitive disturbances and social variables. Speech therapy appears to be useful only for a subgroup of Parkinsonian patients. PMID- 1427554 TI - [Compulsory admission of psychiatric patients in a national and international comparison--incidence and factors of influence]. AB - The frequency of compulsory admissions of psychiatric patients is very variable if compared nationally and internationally. In the old Laender of West Germany, between 2.8% (Bremen) and 44.8% (West Berlin) of all psychiatric admissions were compulsory. The range is even broader, if one compares different western countries: while in Denmark the frequency of compulsory admissions is about 5% of all admissions, it is 50-93% in Switzerland. In this paper the reasons for this wide variation are analysed, making a distinction between "true" and "artificial" differences in frequency. Artificial differences are mainly due to insufficient representativity and comparability of the populations studied. True differences on the other hand are mainly a consequence of the differing legislation in the individual countries and of regional differences in administrative regulations, but also of the situation of mental health care. Apart from analysing these patient-independent factors influencing compulsory admission, the characteristics of patients are studied which are associated with a higher risk of compulsory admission. The relation of these patient characteristics with the factors "danger to oneself or others", which are the prerequisites of compulsory admission in most countries, is discussed. PMID- 1427555 TI - [Relations of model and drug-induced psychoses to schizophrenic diseases]. AB - From the clinical point of view, substance-induced psychosis can be rather similar to schizophrenia. However, the question whether phenomenological resemblances represent similar underlying causal mechanisms is unsolved. Whereas the interest in experimentally induced psychosis was purely academic until the mid-1960s, the widespread use of "recreational" drugs provided this research with an important practical impact. With respect to a given case the differential diagnosis between schizophrenia and drug-induced psychosis it is often problematic. The differences in psychopathology refer to the disturbances of experience in general (Ichstorungen), the character of the hallucinations and the quality and quantity of the alterations of consciousness. Contrary to the sharp distinctions which used to be drawn between schizophrenia and drug-induced psychotic states, we hold that these states are rather similar, and may even represent a common underlying pathology. Hence, the renewed interest in the study on experimentally induced psychotic states using advanced methodology seems justified. PMID- 1427556 TI - [Recent trends in pharmacotherapy of aggressive behavior in psychiatric patients]. AB - Patients with recurrent pathologic aggressive behavior constitute a severe problem for psychiatric institutions. Besides of being dangerous towards others, these patients themselves suffer from a variety of negative consequences, such as the danger of long-term hospitalisation etc. Therefore, pharmacologic treatment in addition to psychotherapeutic and social interventions is not only ethically justified but mostly inevitable. This kind of combined treatment as a rather common procedure in psychiatric institutions leads time and again to fairly high doses of neuroleptics but not to satisfactory results. This article gives an overview of studies on the advantages and drawbacks of alternative substances: Benzodiazepines, beta-blockers, lithium salts, amine precursors and antiepileptics. Differential indications are described. PMID- 1427557 TI - Chondromalacic changes of the patella in rabbits. AB - Malalignments of the patellofemoral joints were artificially made in eleven rabbits using four different methods in order to generate chondromalacia of the patella. Chondromalacic changes and the location similar to the chondromalacia of the human body were generated in one joint of the patching group. According to the results of our investigation, the most reasonable etiological factor of the chondromalacia is thought to be the expansion of the medial retinaculum and capsule of the knee joint, and chondromalacia patellae may not be a precursor of osteoarthritic changes. PMID- 1427558 TI - The measurement of muscle strength in the hip joint expressed by the octagonal diagram. AB - For grasping hip joint function objectively and planning an adequate program for individual use in rehabilitation during and after the treatment for hip joint impairments, the octagonal diagram of the correct distribution of the hip joint muscle strength will be useful. The muscle strength was measured in the eight directions using the Cybex-II on the U.B.X.T. table not only on the peak torque but also on the maximum work and the maximum work/sec in eighty healthy subjects, forty of each male and female. No difference of the muscle strength between the dominant and the non-dominant legs of both male and female has shown. In the percentage of the values of the muscle strength, there are differences between the peak torque, the maximum work value and the maximum work/sec. The data obtained from this investigation will be available to judge the degree of hip joint impairment, and to make a better therapeutic program for the patients. PMID- 1427559 TI - [Two cases of blind pouch syndrome]. AB - Case 1. A 39-yr-old male was presented with anemia. Initial blood examination showed remarkable iron deficiency anemia. Small bowel X-ray and abdominal CT examination revealed a dilated tract at the end of the ileum. Surgical operation was done. The surgical specimen showed side to side anastomosis which was reconstructed at the operation for rt. inguinal herniation 46 days after his birth. The oral side of the tract was remarkably dilated. Case 2. A 50-yr-old male was presented with dizziness. He had anemia and clubbed fingers. A small bowel X-ray examination was done and it showed side to side anastomosis in the middle of the small intestine. Surgical operation was performed. The surgical specimen showed side to side anastomosis about 2 m 20 cm from the Treitz' ligament, which was reconstructed during the operation for ileus when he was 10 years old. The blind portion was remarkably dilated. In both case, the anemia was improved after the operation. PMID- 1427560 TI - [A case of idiopathic hemochromatosis associated with gastric cancer]. AB - A 76-year-old male was admitted to our hospital because of general fatigue in June 1987. He had received total gastrectomy against gastric carcinoma two years previously. The examinations revealed the elevation of GOT, GPT and gamma-GTP, and increased CT number of the liver. Specimen of the liver biopsy showed deposition of iron and slight fibrosis. He was diagnosed as idiopathic hemochromatosis. He was given deferoxamine, and his elevated GOT, GPT and gamma GTP were normalized. Idiopathic hemochromatosis is frequently associated with various malignancies including hepatic carcinoma. However, only a few cases of idiopathic hemochromatosis associated with gastric carcinoma have been reported. PMID- 1427561 TI - Role of asynchronous activation of the ventricular fibres by an ectopic pacemaker in the accidents, especially fibrillation, caused by Ic antiarrhythmic drugs. AB - Class Ic antiarrhythmic drugs, which are known to slow down conduction in the ventricular muscle, are likely to impair synchrony in activity of the ventricular fibres. Asynchronous activation was first investigated between an ischaemic and a normal area by the simultaneous recording in anaesthetized, open-chest pigs of two left ventricular monophasic action potentials (MAPs) under ventricular pacing at a high rate of 180 beats.min-1. Asynchronous activation was then investigated in the intact myocardium according to the distance separating the recording from the pacing electrode. Furthermore, mechanical effects of left ventricular systole were observed by recording dP/dt(max) and mean arterial blood pressure during the pacing periods. Ischaemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin; as a result, activation time reached 85 ms in the ischaemic area under flecainide administered iv in a 2.5 mg.kg-1 dose instead of approximately 60 ms in the normal area for fibres equi-distant from the pacing electrode. Similar delays in activation were observed in the intact myocardium, depending on whether the explored region was close to or far from the pacing electrode. In the latter case, the difference in activation time may become markedly greater if the distance or the dose of flecainide are increased. This difference, which possibly exceeds one-third of the MAP duration (practically unchanged by flecainide), may account for the occurrence of fibrillation or the sudden loss of systole mechanical efficacy. PMID- 1427562 TI - CRL41405: a drug with a new pharmacological profile on pancreatic exocrine secretion in the rat. AB - The recently described compound CRL41405 displays central effects suggesting possible antidepressive and awakening properties. In order to further analyze the pharmacology of this compound, its effects were studied on basal and stimulated pancreatic secretion in anaesthetized rats. CRL41405 alone (7-20 mg/kg, sc) had no effect on basal pancreatic secretion. Larger doses (67-200 mg/kg) increased basal secretion through the stimulation of cholinergic muscarinic receptors, the effect being antagonized by atropine. CRL41405 (20 mg/kg) suppressed the 2 deoxyglucose-induced (but not the acetylcholine-induced) stimulation of pancreatic secretion through an alpha-2 adrenoceptor inhibitory mechanism that was blocked by idazoxan (0.3 mg/kg, sc). In addition, a beta adrenoceptor mediated stimulation of sodium and bicarbonate excretion (blocked by propranolol) was evidenced when the alpha-2 inhibition was suppressed by idazoxan. Under alpha 2 adrenoceptor blockade, water and electrolyte stimulation by CRL41405 could be demonstrated on basal, 2-deoxyglucose-induced and acetylcholine-induced pancreatic secretion. This original profile makes CRL41405 a unique drug in pancreatic pharmacology. PMID- 1427563 TI - Differential effects of cromakalim on pancreatic vascular resistance and insulin secretion in vitro. AB - The effects of the potassium channel opener cromakalim on vascular resistance and insulin output were investigated in vitro within the same experimental preparation, the isolated rat pancreas perfused at a constant pressure with a physiological solution containing 8.3 mM glucose. Cromakalim induced a clear and concentration-dependent dilatory response of pancreatic vessels; the concentration-response curve obtained in the range of 10(-8) - 10(-5) M had a sigmoidal shape with a linear part between 10(-7) and 10(-6) M. Cromakalim did not inhibit insulin release at these concentrations. These results differ from those obtained with diazoxide, which has been previously shown both to inhibit insulin secretion and induce vasodilatation of the pancreatic vascular bed in a similar range of concentrations (10(-6) - 10(-5) M). The data presented provide evidence for a selective effect of cromakalim on pancreatic vascular resistance. Our present and previous results support the view that cromakalim is effective on K+ channels of vascular smooth muscle that differ from the ATP-sensitive K+ channel opened by diazoxide in insulin-secreting B-cells. PMID- 1427564 TI - Could saliva stand for plasma in theophylline monitoring in asthmatic children? Still a controversial problem. AB - Theophylline determination in saliva was proposed several years ago as a convenient and non-invasive alternative to monitoring plasma in children and adults. Published data demonstrated that theophylline saliva concentration linearly correlates plasma concentration. However, the variability found in interindividual serum/saliva ratios and the wide scattering among the data points precluded the clinical use of saliva for theophylline monitoring. The purpose of this study was to compare different standardized methods for obtaining stimulated saliva intending to reduce the variability in plasma/saliva ratios and to determine the most reliable one. A group of 150 ambulatory chronic asthmatic 4.5 to 20.83 (10 +/- 3.7; M +/- SD) year-old patients receiving theophylline 6.85 +/- 1.88 mg/kg every 12 h as slow release preparations for 4 to 100 days was studied. One ml venous blood and salivary specimens were simultaneously collected 5.15 +/- 0.36 h after the morning maintenance dose. In a subgroup of 75 patients, saliva was collected using first a new device called salivette, immediately followed by the collection of an expectorated sample 30 s after citric acid crystals stimulation. In the other patients saliva was collected using citric acid containing salivette. Theophylline concentration was determined using HPLC. For all types of saliva collection, salivary and plasma theophylline concentrations correlated significantly. However whichever method was used, based on the -2 to +2 SD interval, a large range of plasma theophylline was predicted from a single salivary theophylline concentration. Despite a further standardization of the sampling of saliva, saliva theophylline could not accurately predict plasma concentration. PMID- 1427565 TI - Laparoscopic cholecystectomy--the new surgery. PMID- 1427566 TI - Are some cholecystectomies unjustified? PMID- 1427567 TI - Endoscopic retrograde cholangiopancreatography in childhood. AB - ERCP was performed in 19 children and adolescents aged 4 to 16 years. In 13 children the examination was done under general anesthesia, in 6 cases with the usual premedication using dolsin and atropine. Indications for examination were unclear abdominal pain with occasional amylase elevation, in 3 patients status after an abdominal injury. In 16 patients the examination clarified the complaints by detecting organic disease of the gallbladder or the pancreas. ERCP is an important procedure in the event of uncertain diagnosis in children and adolescents and, if the indication is correct, and the technique good, is well tolerated by the patients. PMID- 1427568 TI - Cholecystectomy by minilaparotomy without muscle section: a short-stay procedure. AB - The aim of this prospective study was to assess the results of cholecystectomy performed by an incision characterized by its small size and absence of muscle section, to minimize postoperative discomfort, and shorten hospital stay. Surgical access was via a transverse division of the linea alba extending 1.5-2 cm on the rectus sheath, on both sides, without section of muscle. One hundred and ninety-one patients were operated on. Only 1 (0.5%) peroperative complication (injury of cystic artery) and 4 (2%) benign postoperative complications occurred. The mean postoperative hospital stay was 4.4 +/- 1.7 days (range 2 to 12); for the 90 patients operated on in 1989-1990 it was 3.3 +/- 1.7 days (range 2 to 12). Long-term results were assessed in 113 patients. Only 1 (0.6%) complication occurred, namely migration of a retained common duct stone. Neither incisional hernias nor a need for reoperation occurred. The cosmetic results were assessed by the patients themselves as very good in 95 (84.1%) cases and good in 16 (14.2%) cases. PMID- 1427570 TI - Management of postoperative bile leakage with endoscopic sphincterotomy (EST) and a naso-biliary drain (NBD). AB - Between July 1987 and December 1990, 13 patients with postoperative bile leakage were treated with endoscopic sphincterotomy and a naso-biliary drain. All the leaks healed in two weeks, except for one (intrahepatic) that needed two months to heal in association with percutaneous management. The non-surgical treatment of bile leakage is the preferred approach on account of the superior safety, efficacy and cost-effectiveness as compared with surgical repair, which is associated with significant morbidity, mortality and costs. The treatment of choice has to be endoscopic, which is much easier and safer than the transhepatic approach, especially in the non-dilated duct, while another advantage over radiology includes the possibility for rapid definitive treatment of distal obstruction (e.g. residual stones). A leak from an extrahepatic duct heals rapidly, while a leak from an intrahepatic duct takes longer to heal and sometimes needs associated percutaneous drainage. Finally, the authors propose treating an extrahepatic bile leak merely with naso-biliary drainage without cutting the papilla, and an intrahepatic bile leak with endoscopic sphincterotomy, nasobiliary drainage and a bilio-duodenal endoprosthesis. PMID- 1427569 TI - Percutaneous transhepatic biliary drainage in patients with malignant biliary obstruction of the hepatic confluence. AB - Despite many studies on percutaneous transhepatic biliary drainage (PTBD), there are no satisfactory reports of PTBD for malignant obstruction of the hepatic confluence. In this study, the results of PTBD using the direct anterior approach under fluoroscopic guidance are described in 16 patients with malignant biliary obstruction of the hepatic confluence. A total of forty-two drainage catheters were placed in the 16 patients: one catheter was placed in three patients; two catheters in six; three catheters in four; four catheters in two; seven catheters in one. PTBD was successful in 100% of the cases with no mortality or critical complications, and the biliary decompression effect of PTBD was highly satisfactory. Nine patients underwent histologically curative hepatectomies. Two of the nine resected cases died of postoperative hepatic failure, but the postoperative course in the others was satisfactory. The authors stress that selective biliary drainage for each isolated segmental duct is mandatory for advanced malignant obstruction of the hepatic confluence. PMID- 1427571 TI - Critical evaluation of the anastomoses in large bowel surgery: experience gained in 533 cases. AB - We critically examined the morbidity and mortality of manual and stapled colorectal anastomosis in a retrospective study of 533 patients who underwent colorectal resection for neoplastic and non-neoplastic disease. The clinically detected anastomotic dehiscence rate was 4.5%, and the mortality rate 1.8%. The extraperitoneal site of the anastomosis after rectal anterior resection with stapled anastomosis and surgery for cancer showed a statistically significant predisposition to anastomotic dehiscence. Age, emergency surgical intervention, curative versus palliative resection, the location of the anastomosed intestinal segments, type of anastomosis and presence of a protective colostomy did not appear to be statistically significant factors for anastomotic dehiscence. While the stapler may offer an advantage in the individual case, the low incidence of morbidity and mortality for manual anastomosis in this study reaffirms the soundness and importance of the manual colorectal anastomosis in the surgeon's technical armamentarium. PMID- 1427572 TI - Experimental model with bilioenteric anastomosis in rats--technique and significance. AB - A simple technique of hepaticojejunostomy in rats is introduced in this paper and its suitability for use as an experimental model was evaluated histologically. Hepaticojejunostomy was performed as follows; the stump of the supra-pancreatic common bile duct (CBD), detached from adjacent tissue, was introduced into the jejunal lumen using the outer catheter previously inserted into the jejunum, and the jejunal wall close to the implantation site of the CBD was fixed to the porta hepatitis with a suture. Among 40 rats in which hepaticojejunostomy was performed, the postoperative mortality rate was 17.5%. The remaining experimental animals (33 rats, 82.5%) survived for the duration of this study. The rats were sacrificed at 3, 5, 8, and 12 months after surgery, and liver function tests, macroscopic and histological studies of the biliary tract were carried out. No signs of cholangitis or liver abscess were noted in any experimental animals during this period. The median values of liver function tests were within normal limits in almost all of the experimental rats. The anastomotic stoma was also patent, and free drainage of bile was noted, but the bile duct proximal to the site of anastomosis was generally macroscopically dilated. Histologically, epithelial hyperplasia and fibrous thickening of the wall accompanied by inflammatory cell infiltration were noted in the rats sacrificed at 3 and 5 months postoperatively. Marked hyperplasia of mucous glands, goblet cell metaplasia and atypical epithelium were usually seen in the rats killed at 8 months and 12 months after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427573 TI - A new liver and soft tissue biopsy instrument. AB - A new liver biopsy instrument taking the form of a suction biopsy syringe with two pistons and a Menghini needle, is described. A vacuum is first created, and the whole procedure is effected by a continuous uninterrupted movement into the liver and instantaneous withdrawal. The syringe is held in one hand. The procedure is very simple and requires minimal training. A total of 118 biopsies have been performed. The specimens were suitable for histopathological examination. Pain was minimal and there were no complications. PMID- 1427574 TI - Hepatic encephalopathy secondary to a large-caliber porto-hepatic venous shunt. A case report. AB - A case of hepatic encephalopathy secondary to a large-caliber porto-hepatic venous shunt in a 61-year-old woman with gastric cancer is reported. Mild confusion, flapping tremor and hyperammonemia were noted preoperatively. Abdominal ultrasonography showed a large-caliber porto-hepatic venous shunt in the left lateral segment of the liver. Percutaneous transhepatic portography and superior mesenteric angiography were confirmatory. Intraoperative portal scintigraphy was performed before and after temporary shunt occlusion to measure the intrahepatic shunt rate, which decreased markedly after occlusion. Portal pressure was also measured, and increased only slightly after occlusion. Left lateral hepatic segmentectomy, and subtotal gastrectomy with splenectomy were performed. Hepatic encephalopathy resolved postoperatively. The shunt was thought to be acquired. The relevant reports on large-caliber porto-hepatic venous shunts in the literature are reviewed. PMID- 1427575 TI - Primary sarcoma of the liver in the adult. Report of five surgically treated patients. AB - During the 5-year period between 1988 and 1989, five patients with primary sarcomas of the liver underwent surgery. Since the patients presented in an early stage of the tumor, all the sarcomas were resectable, in three cases with wide margins (R-0 resection). Five histological types were detected: malignant hemangiopericytoma, malignant fibrous histiocytoma, hemangiosarcoma, rhabdomyosarcoma, and embryonal sarcoma. Two patients with high-grade sarcomas received adjuvant chemotherapy. The follow-up was favorable in three patients with R-0 resections (two had adjuvant chemotherapy). They were still alive, with no evidence of disease 30, 46, and 63 months after the diagnosis. The two other patients had to be reoperated on for local recurrences. Both died of their tumor disease, 30 and 35 months after the initial diagnosis. Extensive chemotherapy in one of these cases failed to arrest tumor progression. Hence, liver resection with wide margins is a very important measure in such cases. PMID- 1427576 TI - Medical treatment of reflux esophagitis. PMID- 1427577 TI - Immunotherapy of chronic active viral hepatitis B with propionibacterium granulosum KP-45 (a 5-year follow-up report). AB - In the period 1982 to 1984, 14 HBS-AG-positive patients with chronic active hepatitis B were treated monthly with a cell wall preparation (5 or 10 mg) of Propionibacterium granulosum KP-45 (PG), intravenously administered for a period of 6 to 10 months. All 14 patients were monitored by serological and biochemical tests as well as liver biopsy two, three and five years after completing immunotherapy with PG. During this period the patients received neither a specific antiviral, corticosteroid or interferon therapy, nor PG. Re-appearance of HBSAG or HBeAG was never seen in patients who were already free from the antigens one year after completing PG immunotherapy. During the 5-year follow-up, spontaneous improvement in serological and morphological (liver biopsy) parameters of chronic virus B hepatitis occurred in six patients. Five years after completion of PG immunotherapy, only four of the 14 patients showed trace amounts of serum HBSAG (carriers), and in two low levels of anti-HBeAG were present, while the whole group showed a decreasing tendency and serum anti-HBc was still detectable in six patients. HBeAG- and DNA-polymerase-positivity was absent in all patients. Microscopic examination of liver biopsies 5 years after PG immunotherapy showed mild symptoms of chronic hepatitis with inflammatory infiltration, non-active cirrhosis, but without massive periportal and/or multilobular necrosis and trace amounts of HBsAG and HBcAG in hepatocytes only in the four carriers. The remaining 10 patients were free of symptoms of active hepatitis and/or active cirrhosis, but all the patients had moderate to intensive fibrosis in their liver biopsies. PMID- 1427578 TI - Hyperbilirubinemia, jaundice and anergy. AB - A prospective study of delayed hypersensitivity response was carried out in jaundiced patients. One hundred and seventy-seven subjects were studied. Fifty nine were controls and one hundred and eighteen were patients with hepato pancreato-biliary pathology and biliary tract obstruction. A multitest technique was used to evaluate the delayed hypersensitivity response, classifying the subjects into one of three groups: immunocompetent, relatively anergic and anergic. In the control group 76.3 per cent of the subjects were immunocompetent as opposed to 16.1 per cent of the patients (p less than 0.0001). Twenty-four per cent of the control subjects and eighty-four per cent of the patients presented anergy or relative anergy (p less than 0.0001). Among the patients no difference could be found in the index of anergy between malignant and benign pathology. We have found, moreover, that patients with a mean bilirubin level of 12 mg/dl showed a change in the delayed hypersensitivity response, with development of anergy or relative anergy. PMID- 1427579 TI - Indications and results of hepaticojejunostomy in benign strictures of the biliary tract. AB - The postoperative and late results of 99 patients with benign strictures of the biliary tract are presented. Patients were classified according to Bismuth into 24 cases with lesion type I, 36 cases with type II, 35 cases with type III and 4 patients with type IV. All were submitted to hepaticojejunostomy with a long Roux en-Y loop. The etiology of the strictures varied according to the type of stricture. In patients of type I, inflammatory and iatrogenic causes were observed. Among type II and III patients, previous cholecytocholedochal fistulas were the main cause, together with accidental section or ligature of the common bile duct. Operative mortality was absent in strictures of types I and II, while it was around 25% in cases of types III and IV. At late control, the best results were seen among patients with strictures of types I and II. We believe that the main factor determining the early and late outcome of these cases with benign strictures is the location of the stricture and the quality of the proximal duct. PMID- 1427580 TI - A comparison between antipyrine and aminopyrine blood clearances. AB - The purpose of this study was to investigate the relationship between two quantitative liver functions, that is, antipyrine blood clearance and aminopyrine blood clearance, in normal subjects and in patients with liver cirrhosis. The mean blood clearances of antipyrine and aminopyrine in cirrhotic patients (0.220 +/- 0.085 ml/min/kg and 1.13 +/- 0.56 ml/min/kg; n = 64) was 50% and 38% of that of normal subjects (0.440 +/- 0.110 ml/min/kg and 2.95 +/- 0.59 ml/min/kg; n = 11). While no significant correlation was demonstrated between these two values in normal subjects (n = 11, r = -0.107, p greater than 0.10), a strong positive correlation was observed between antipyrine and aminopyrine blood clearances in cirrhotic patients (n = 64, r = 0.846, p less than 0.001). These results suggest that both antipyrine and aminopyrine blood clearances may be valuable indicators for assessing the total hepatic functioning mass in cirrhotics. PMID- 1427581 TI - Surgery in cholangitis: bacteriology and choice of antibiotic. AB - Owing the frequent occurrence of intrahepatic stones in orientals, cholangitis presents a real problem. Surgery and antimicrobial drug therapy are the main forms of treatment. A retrospective study of choledochotomy, including biliary tract surgery, performed between July 1987 and June 1990, was conducted. Cases with negative common duct exploration during cholecystectomy were excluded. Among 186 cases, 128 (68%) had positive bile growth, which was defined as cholangitis. Sepsis-related complications occurred in 51 patients (27.4%), including 3 surgical deaths, 30 wound infections, and 18 others. The complication rate was higher in the cholangitis group than in the negative group (37.5% vs. 5.2%). However, if peri-operative antibiotics were effective against the cultured bacteria species, the complication rate was 16.9%; if not, the complication rate was 85.3%. For the different-generation cephalosporins used in the peri-operative period, the complication rates were 32.2%, 20.8%, and 27.6% each for 1st, 2nd, and 3rd generation cephalosporins, with no statistically significant differences. In microbiological study, polymicrobial infection was the rule. On average, 2.3 species were grown from each specimen. Enterococcus proved the most important species with a 54% culture rate. E. coli and Pseudomonas were important gram negative bacilli, with culture rates of 46.1% and 39.1%, respectively. Anaerobic species were cultured in 12.3% of the patients. For good coverage of cholangitis prior to operation, the proper antibiotic should have potency against gram positive Enterococcus, gram-negative bacilli, especially Pseudomonas and E. coli, and anaerobic species, especially Bacteroides. PMID- 1427582 TI - Amikacin once daily plus metronidazole versus amikacin twice daily plus metronidazole in colorectal surgery. AB - Amikacin administered once a day plus metronidazole is compared with amikacin given twice a day plus metronidazole in colorectal surgery (prophylactic or therapeutic antibiotic treatment). A total of 325 patients were studied in this randomized multicenter trial. The results of this trial suggest that a single daily dose of amikacin is equally as effective in combating infectious postoperative complications as twice a day administration. The side effects were similar, with the exception of renal effects, which were somewhat more pronounced in once a day amikacin administration. Nevertheless, all the renal function alterations were transient and we observed no definitive renal insufficiency. PMID- 1427583 TI - The impact of early or late diagnosis on patient survival in gastric cancer in Greece. AB - The purpose of this study was to investigate the reasons for delayed diagnosis of gastric cancer in the Greek population and correlate survival with early or late diagnosis. We studied 100 patients with gastric cancer proven at endoscopy. Early diagnosis (less than 3 months from the onset of symptoms) was established in 28 patients (28%), while the diagnosis was late (greater than 3 months) in 72 patients (72%). The reasons for late diagnosis were: 1. delayed consultation on the part of the patient, 2. incorrect medical diagnosis at a) initial evaluation, b) radiological evaluation and, as a result, c) failure to refer for endoscopy and biopsy. Patient survival correlated well with tumor resectability, irrespective of early or late diagnosis. In patients with early diagnosis and resectable tumor survival was 9.9 +/- 4.8 months (mean +/- SD) whereas with non resectable tumor 4.8 +/- 4.0 months (p less than 0.01). In patients with late diagnosis, survival in resectable tumor was 13.5 +/- 11.7 months compared with 8.5 +/- 6.9 months in non-resectable tumor. No correlation was noted between survival and anatomic location of tumor or degree of histologic differentiation. Early diagnosis of gastric cancer is associated with a higher degree of resectability and therefore of better survival. PMID- 1427584 TI - Chief cell mass after short-term ranitidine treatment for duodenal ulcer. AB - The chief cell mass and the parietal cell mass were evaluated in endoscopically obtained biopsy specimens of fundic mucosa from 15 duodenal ulcer patients before and after ranitidine treatment. Patients were given ranitidine, 300 mg/day, for 8 weeks. Chief cell mass and parietal cell mass were expressed respectively by a "zymogenous index" (ZI) and a "parietal index" (PI), obtained by multiplying the number of cells per mm2 by the thickness of the glandular layer. From the results of this study it would appear that, in patients with duodenal ulcer, treatment with ranitidine at a dose of 300 mg/day for 8 weeks results in a significant increase in parietal cell mass and a decrease in chief cess mass. PMID- 1427585 TI - Major bacterial infections following liver transplantation: a prospective study. AB - The incidence and characteristics of major bacterial infections were studied prospectively in 50 consecutive adult patients who underwent liver transplantation (LT). All patients received the same protocol of immunosuppression, bowel decontamination, antibiotics prophylaxis, and follow-up. Thirty-two patients (64%) had at least one episode of major bacterial infection. One death was directly related to a bacterial infection, accounting for 13% of postoperative mortality. The most critical period for infection was the first 2 months after surgery, when 69% of the infections occurred. The most frequent clinical presentations were bacteremia, pneumonia and abdominal abscesses. Eighty percent of the bacteremias had an identifiable source, the most frequent being intravascular catheters. Gram-positive microorganisms (69%) predominated over gram-negative rods (26%) and anaerobes (5%). The use of selective bowel decontamination (SBD) with norfloxacin may explain this predominance. Major bacterial infections are an important source of morbidity and mortality after LT. Efforts to prevent these infections and to determine their source and specific treatment, will improve the management and the outcome of these patients in the future. PMID- 1427586 TI - Gastric acid secretion and plasma gastrin during short-term treatment with omeprazole and ranitidine in duodenal ulcer patients. AB - The aim of this study was to evaluate changes in peptic acid secretion, and in fasting and meal-stimulated plasma gastrin levels after a 7-day course of omeprazole 30 mg/day or ranitidine 300 mg/day, administered in accordance with a randomized, double-blind, double-dummy protocol. Ten duodenal ulcer patients were studied. Their acid and pepsin output was determined prior to and after treatment. Plasma gastrin levels were also determined under basal conditions on day 7 of treatment, and 24 hours after the last administration of the drug. With regard to acid output, omeprazole resulted in a 98% reduction in BAO and an 80% reduction in PAO, both significantly greater than those achieved with ranitidine (BAO 50%, PAO 25%). No significant changes in pepsin secretion were observed. The increase in fasting plasma gastrin observed after ranitidine and omeprazole was 86% and 242%, respectively, on day 7, and 13% and 103% twenty-four hours after final dose. Increases in meal-stimulated plasma gastrin were, respectively, 126% and 125% on day 7 and 8 after omeprazole, whereas the increase with ranitidine was 62% only on day 7 of treatment, with subsequent normalization. In addition to confirming the well-known effect of omeprazole on the physiology of gastric secretion, our data show that administration of therapeutic doses of traditional H2-antagonists is accompanied by a secondary hypergastrinemia, which is rapidly reversible after discontinuation of therapy. PMID- 1427588 TI - [Diagnosis and treatment of familial hypercholesterolemia]. PMID- 1427587 TI - Cholesterol polyp of the gallbladder showing rapid growth and atypical changes--a case report. AB - We report on a case of resected cholesterol polyp with typical ultrasonic findings that became atypical, with a 40% increase in diameter, over a period of about 10 months. The resected specimen revealed a black polyp with a large nodular appearance. The pathological diagnosis was cholesterol polyp with marked glandular proliferation, and the glandular cavity showed cystic dilatations filled with dark brown fluid. It is suspected that the aggregation of large numbers of these dilated glands explained the black color, the rapid growth, and the development leading to the atypical ultrasonic findings. PMID- 1427589 TI - [Signal transduction through antigen-specific receptors of lymphocytes: activation of phospholipase C by protein-tyrosine kinases]. PMID- 1427590 TI - [The role of endogenous cytokines in pathophysiology of various human diseases]. PMID- 1427591 TI - [Current topics on dialysis therapy with special reference to diabetic nephropathy]. PMID- 1427592 TI - [Effect of pretreatment with N-methyl-N-nitrosourea or streptozotocin on the cytotoxicity and the induction of sister chromatid exchanges in human and rodent brain tumor cells treated with chloroethylnitrosourea]. AB - Effects of pretreatment with N-methyl-N-nitrosourea (MNU) or streptozotocin (STZ) on cytotoxicity and induction of sister chromatid exchanges (SCE) in human and rodent brain tumor cells treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 1-(2-chloroethyl)-1-nitrosourea (CNU) were investigated. 9L-2 and SF-188 cells were more resistant to the cytotoxic effects of chloroethylnitrosourea than 9L and SF-126 cells. SF-295 cells were more resistant to the cytotoxic effects than SF-126, but more sensitive than SF-188 cells. Pretreatment of 9L-2 cells with MNU or STZ resulted in a dose-dependent increase in cytotoxicity and SCE induction by BCNU. Treatment with 1mM MNU or 1.5mM STZ completely reversed the cellular resistance of 9L-2 cells to BCNU but did not potentiate either cytotoxicity or SCE induction in 9L cells. Pretreatment of SF-188 and SF-295 cells with MNU or STZ resulted in a dose-dependent increase in cytotoxicity and SCE induction by CNU. Treatment with 500 microM MNU or 1.5mM STZ for SF-188 cells, and with 250 microM MNU or 1.5mM STZ for SF-295 cells completely reversed the cellular resistance to CNU. These results are consistent with the hypothesis that pretreatment with MNU or STZ inhibits O6-alkylguanine-DNA-alkyltransferase (O6 AT) and inhibition of the enzyme allows the formation of DNA interstrand cross links resulting in increase in cytotoxicity and induction of SCE in resistant cells treated with chloroethylnitrosourea. In this regard, O6-AT plays an important role in determining the cytotoxicity and induction of SCE by chloroethylnitrosourea in both rodent and human brain tumor cells. PMID- 1427593 TI - Studies on mitochondrial and microsomal phospholipids and phospholipase A2 in heart from rats subjected to prolonged exercise. AB - Alterations in phospholipids and phospholipase A2 activity produced in cardiac mitochondria and microsomes by prolonged exercise and the effect of quinacrine on these changes have been studied in two types of experiment done on rats subjected to prolonged swimming exercise. In Experiment I, rats swam for 0.5, 1.5 or 3 h carrying a weight representing 3% of body weight. At the end of exercise or after varying recovery periods, the hearts were removed, mitochondria and microsomes were isolated and phospholipid constituents, cholesterol and phospholipase A2 (PLA2) determined. The phosphatidylethanolamine (PE) and phosphatidylcholine (PC) levels in mitochondria were progressively reduced by exercise for 0.5, 1.5, and 3 h as compared with control rats (the rats which trained to swim with loading for 4 days and took rest for 1 night). After recovery periods of 6 and 12 h, levels were partially restored, but after 24 and 48 h they decreased slightly below the control values. By 120-240 h, PE and PC levels recovered to slightly higher values than control. In microsomes, PE and PC levels were also decreased at the end of exercise for 0.5, 1.5, or 3 h, but over recovery periods of 6 to 48 h, they gradually increased and stabilized. In Experiment II designed to study the cause of the exercise-induced decrease in PE and PC, intravenous quinacrine was used to inhibit PLA2. PE and PC in exercised rats injected with saline (ES group) were markedly decreased after prolonged exercise when compared with control rats injected with saline (CS group). In exercise rats injected with quinacrine (EQ group), PC was significantly decreased when compared with the CS group while PE was slightly decreased but was not significantly different. Total activity (TA) and specific activity (SA) of PLA2 in mitochondria did not differ significantly in the three groups. In microsomes, TA in the ES group was significantly increased compared with the CS group while that in EQ group was slightly increased but was not significantly different. SA was unchanged in three groups. These results suggest that quinacrine can partially prevent the decrease of phospholipid and partially inhibit the activity of PLA2 after prolonged exercise. RCR in ES group increased significantly after prolonged exercise while RCR in EQ group tended to increase. ADP/O ratio was not significantly different in all groups. PMID- 1427594 TI - [In vitro and in vivo immunobiological responses of glioblastoma to human natural tumor necrosis factor-alpha]. AB - Biological effects of human natural tumor necrosis factor-alpha (TNF) on glioblastoma cells in vitro and on glioma patients were investigated. TNF treatment on glioblastoma cells, even at a high dose (256 U/ml), exhibited no remarkable cytocidal activity in MTT assay, but at lower doses significantly inhibited colony forming and DNA synthesis. TNF at a low dose (10 U/ml) stimulated production of prostaglandin E2, Mn-superoxide dismutase, interleukin (IL)-6 and IL-8 by glioblastoma cells. These results indicated that the direct effect of TNF on human glioblastoma cells is rather antiproliferative than cytotoxic and is to modulate their metabolic pathways. In an early Phase I clinical trial, TNF was administered intracranially to six patients bearing glioblastoma. In this trial, the author studied in vivo immunological responses in the cerebrospinal fluid and regional fluid after the regional TNF injections. TNF in these body fluids were detected with a half life of several hours. There occurred a substantial number of leukocyte migration after the TNF administration. Neutrophils appeared first peaking at 8 to 12 hours, and then CD4+CD8-T cells and CD11b+CD13+CD14+ monocytes followed. IL-8 activity in the cerebrospinal fluid simultaneously corresponded to peak of the neutrophil migration. Increases in IL-6, IL-1 beta and prostaglandin E2 levels in the cerebrospinal fluid, regional fluid or both occurred peaking at 8 to 12 hours after TNA infection. Neither IL-2 nor interferons was detected. In conclusion, TNF may act as an antineoplastic agent by its direct cytostatic effects and indirectly through immune modulatory effects. PMID- 1427595 TI - [The effect of oxygen free radical scavenger on endothelial cell at ischemic and reperfusion injury]. AB - Although a lot of investigations indicated that free radical scavengers, such as superoxide dismutase (SOD) and catalase, reduced ischemia-reperfusion injury, the precise mechanism including the sites of action are still controversial. The purposes of this study were to investigate the sites of action of SOD and catalase by assessing postischemic cardiac and endothelial cell function. Wistar rats (450-550g) were used as support animals to establish blood perfused circuit. A peristaltic pump controlled the femoral arterial supply at 3.0 ml/min and the venous return to the jugular vein with gravity. Hearts (n = 8/group) from the Wistar rats were perfused (Langendorff model) and paced at 350 beats/min. After assessing baseline functions, hearts were rendered ischemia at 37.5 degrees C for 20 min. Then hearts were reperfused for 35 min, at the end of which left ventricular functions were re-assessed. One group of hearts received a continuous infusion of SOD and catalase during the period of 10 min before ischemia to 20 min after the onset of reperfusion. Left ventricular functions were measured with a left intraventricular balloon. The end-diastolic pressure was fixed at 10 mmHg, which was equivalent to the normal left ventricular end-diastolic pressure. The mean postischemic recovery of the left ventricular end-systolic pressure was increased from 55 +/- 3% in the control group to 67 +/- 2% in the SOD and catalase group (P less than 0.05). Similarly, the postischemic compliance was increased from 1.28 +/- 0.12 (microliters/mmHg) in the control group to 1.61 +/- 0.11 (microliters/mmHg) in the SOD and catalase group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427596 TI - [Sulfolipids and glycolipid sulfotransferases in a human renal cell carcinoma cell line]. AB - A cell line (SMKT-R3) established from renal cell carcinoma was characterized by sulfolipids and glycolipid sulfotransferases. It was found by analyzing glycolipids extracted from SMKT-R3 cells that sulfolipids constituted a large part of acidic glycolipids. When SMKT-R3 cells were metabolically labeled with sodium [35S]sulfate, the incorporation of the radioactivity was detected in accordance with SM4, SM3 and SM2, which were major sulpholipids found in the cells, by autoradiography of thin layer chromatogram of the acidic glycolipid extracts from the cells. Markedly high activity level of glycolipid sulfotransferases toward GalCer and LacCer as substrates was observed in SMKT-R3 cells. Effects of 12-0-tetradecanoylphorbol-13-acetate (TPA) and a protein kinase C inhibitor on glycolipid sulfotransferases were investigated in SMKT-R3 cells. The treatment with TPA caused a dose- and a time-dependent reduction of the enzymes activities. Similarly, H-7 and staurosporine, which are inhibitors of protein kinase C, reduced the glycolipid sulfotransferase activities. These results indicate that the glycolipid sulfotransferase activities are mediated by protein kinase C in SMKT-R3 cells. On the other hand, the treatment of SMKT-R3 cells with epidermal growth factor (EGF) was associated with the increase of the glycolipid sulfotransferase activities in a dose-dependent manner. However, this effect of EGF was counteracted by the pretreatment with TPA or H-7. These findings suggest that EGF induces the glycolipid sulfotransferase activities through protein kinase C. PMID- 1427597 TI - [Establishment and characterization of human lung squamous-carcinoma sublines resistant to cis-diamminedichloroplatinum (II)]. AB - I have established human lung squamous-carcinoma cell lines resistant to cis Diamminedichloroplatinum (II) (CDDP), designated PC10-B3 and PC10-E5, from the original cell line PC10, by a stepwise increment of CDDP concentration. An MMT assay revealed that PC10-B3 was 11.4-fold, and PC10-E5 was 19.9-fold more resistant to CDDP than PC10, respectively. PC10-B3 was cross-resistant to CBDCA and 254-S, but not to doxorubicin and etoposide. The level of intracellular platinum accumulation was reduced by about 5 to 8-fold in PC10-B3 when compared with PC10. A two-dimensional gel electrophoresis was used to analyse the relative amount of proteins as between PC10 and its CDDP resistant sublines. The protein spot MW50 kD, pI5.3 was markedly reduced, and the spot MW50kD, pI4.9 was increased in PC10-B3 and PC10-E5 when compared to PC10. The spot MW58kD, pI5.8 newly appeared only in PC10-E5. I collected the most dramatically changed spot, MW50kD, pI5.3 (50kD-5.3), and processed it to determine its peptide sequence. I found that 50kD-5.3 was identical to 50kD, type I keratin (K14). Moreover, a retinoic acid-mediated K14 reduction was concomitant with a 4.0-fold transient increase in CDDP resistance in PC10. Taken together, the reduced intracellular platinum accumulation and the marked decrease of K14 imply that they are important factors in contributing to CDDP resistance in PC10-B3. PMID- 1427598 TI - [Analysis of acute graft-vs-host like reaction in [B6-lpr----B6] spleen chimera mice]. AB - The lpr autoimmune mice develop massive lymphadenopathy and autoimmune disease. Transfer of lpr autoimmune disease to normal mice by bone marrow transplantation did not succeed, but caused a severe wasting syndrome like graft-vs-host (GvH) disease (lpr-GvH). We previously demonstrated that the transfer of B6-lpr spleen cells to B6 mice ([B6-lpr----B6] chimera) caused acute GvH-like disease accompanied by remarkable CD8+ T cell expansion, and that chimera spleen cells had suppressive activity on mitogen responses of spleen cells from normal mice. In this paper, I studied strain difference of acute lpr-GvH disease and mechanism of suppressive activity further. [B6-lpr----B6] chimera spleen contained more than 70% of CD8+ cells. However, [MRL-lpr----MRL-(+)] chimera and [C3H-lpr--- C3H] chimera contained less than 20% of CD8+ cells. Both B220+ DN T cells and CD 8+ T cells were requisite for expansion of CD8+ T cell in the chimera spleen. Mixed chimera experiments using CD8+ T cells from B6-lpr-Thy1.1 mice and B220+ DN T cells from B6-lpr mice showed that CD8+ but not B220+ DN T cells were direct precursors of expanding CD8+ T cells. The mechanism of suppressive activity on Con A responses was different from that on LPS responses. A cell-to-cell interaction was essential for suppression of Con A response without involvement of CD8- cells, while suppression of LPS responses was mainly exhibited by soluble factors. Suppression of LPS responses was abrogated by the presence of anti-IFN gamma monoclonal antibody, suggesting that those factors contain IFN-gamma. These data suggest that CD8+ T cells from B6-lpr mice were activated by unidentified antigen(s) which were expressed by B6 but not B6-lpr cells, and that IFN-gamma and/or unknown inflammatory factors secreted by the CD8+ T cells induced pathological outcome indistinguishable from GvH reaction in B6 recipient mice. PMID- 1427599 TI - [Biochemical study on steroid sulfatase and its clinical application to the obstetrics and gynecology]. AB - Steroid sulfatase desulfates a number of 3 beta-hydroxysteroid sulfates, converting inactive steroid hormone to the active form. I have developed an enzyme-linked immunosorbent assay (ELISA) using polyclonal antibody against the sulfatase which was purified from human placenta to measure an amount of the enzyme protein in sera of gynecologic cancer patients. By this method, it was found that the serum steroid sulfatase level is significantly elevated in patients with endometrial carcinoma (p less than 0.05) and ovarian carcinoma (p less than 0.01) as compared to that of normal women. Steroid sulfatase deficiency, X-linked ichthyosis (XLI) is an inherited skin disorder. The sulfatase gene and the enzyme protein were examined in patients with XLI. When the first and last (exon 10) exons of the sulfatase gene were amplified by PCR using patients' genomic DNA as templates, no product was detected in all six cases examined. In addition, neither mRNA of the sulfatase nor the enzyme protein was detected in a patient with XLI. These observations suggest that most Japanese XLI patients are caused by an extensive deletion of the steroid sulfatase gene. PMID- 1427601 TI - [Analysis of polymorphism at the human class I MHC locus, HLA-G]. AB - HLA-G is one of the non-classical HLA class I gene and its expression has been identified in cytotrophoblasts and in some choriocarcinoma cell lines. It encodes apparently non-polymorphic antigen and is considered to play an important role in the fetomaternal immune system. However, the monomorphism of the HLA-G gene has not been established firmly. In order to examine the polymorphism of the HLA-G locus, a clone 7.0E was isolated from a genomic library using a probe derived from 3' untranslated region of HLA-G (Orr). Additionally, PCR/SSCP analysis of the HLA-G 3' untranslated region was carried on 35 DNA samples of unrelated individuals taking advantage of the fact that HLA-G (Orr) and 7.0E differed in 14bp length in the amplified fragments. The nucleotide sequence of 7.0E was homologous to HLA-G (Orr), but the sequence was more closely related to a cDNA sequence of BeWo-G7 which has been cloned from mRNA of BeWo cells. Among these 3 clones no amino acid substitution was found in the coding region, Thus, 7.0E should represent a genomic clone of BeWoG7. PCR/SSCP analysis showed that 33 out of 35 samples (94%) contained 7.0E gene, 29 contained HLA-G (Orr) gene (83%). Two samples (6%) contained only HLA-G (Orr), and 6 samples contained only 7.0E (17%). Among 29 DNA samples containing HLA-G (Orr), 3 samples showed the shift in electrophoretic mobility in HLA-G (Orr), suggesting minor sequence differences in HLA-G alleles. From these results it is concluded that HLA-G antigen is monomorphic, but there are several alleles recognizable by DNA sequence and/or SSCP analysis. PMID- 1427600 TI - [Synergism between transcription factors NF-IL6 and NF-kappa B in IL-6 gene regulation]. AB - NF-IL6 and NF-kappa B are nuclear proteins supposed to play an important role in the regulation of acute-phase protein synthesis and inflammatory response against infection and tissue injury as a host defence mechanism. In addition the promoter region of the interleukin-6 (IL-6) gene has a NF-kappa B binding motif as well as a NF-IL6 binding site. Considering of these facts, we come to investigate that there may be a synergistic effect between NF-IL6 and NF-kappa B in the regulation of IL-6 gene expression. In order to study it, some combinations of expression vectors NF-IL6 cDNA, NF-kappa B (p50/p65) cDNA and reporter plasmid K18-CAT which contains human IL-6 promoter linked to the chloramphenicol acetyltransferase (CAT) gene, were transfected into Jurkat cells and the CAT activities were examined. Co-transfection of NF-IL6 and NF-kappa B (p50/p65) cDNA revealed a dramatic increase of acetylated [14C] chloramphenicol, and its CAT activity reached to 40%. Then, co-transfection of NF-IL6 and NF-kappa B subunit p65 alone showed a high level of CAT activity, too. When 5' deletion mutant reporter plasmid K9-CAT lacking the NF-IL6 binding site was used, co-transfection of NF IL6 and NF-kappa B (p50/p65) showed low level of CAT activity. These results indicate that there is a synergistic effect between NF-IL6 and NF-kappa B (p50/p65) in IL-6 gene regulation. Among two subunits of NF-kappa B (p50/p65), p65 seems to play an important role rather than p50 does in synergism between NF IL6 and NF-kappa B. Besides, this synergistic function comes to work only when NF IL6 binds to its binding site of IL-6 promoter region. PMID- 1427602 TI - [Identification of molecular species in porcine luteal glutathione S-transferase and its hormonal regulation by hypophyseal gonadotropins]. AB - The glutathione S-transferase (GST) was purified to homogenous state from cytosol fraction of porcine corpora lutea. Present studies showed that the final enzyme preparation was consisted of a single molecular species of GST 1-1 (ligandin), which has been identified from its enzymatic properties, amino acid sequences and immunological reactivity. Furthermore, it has been suggested that the ovarian GST involves in the steroidogenesis, especially in the step of progesterone synthesis, from the following results. 1) The final enzyme preparation has a significant delta 5-3-ketosteroid isomerase activity. 2) GST activity in the cultured porcine granulosa cells was remarkably increased in the luteinizing process, which was induced by an addition of hypophyseal gonadotropins such as FSH and LH to the culture system. 3) Changes of GST activity induced by FSH and LH were closely associated with progesterone production. 4) The GST localized in the luteal cells and theca interna, but not in the granulosa cells, which has been revealed by an immunohistochemical staining using anti-luteal GST antibodies. PMID- 1427603 TI - [A cardiodynamic study on cardio-assistive effect of the assist device: evaluation on left ventricular dehematizing system]. AB - Of late years, assist artificial heart device has been more and more investigated with subsequent reports being made of its clinical application. Dehematization of left ventricular assist device (LVAD) is divided into two systems, i.e., left atrial dehematization and left ventricular dehematization according to the location of the canula's tip. At present in our country, the former system is being adopted for the majority of LVADs and is generally regarded as preferably acceptable. However, because of low survival rate of LVAD in spite of its comparatively good rate of break-away, not a few cases appear to exist beyond the limit of the former system's effects. Then, compared with the left atrial dehematizing system, LVAD according to the left ventricular dehematizing system was examined for its cardio-assistive effect both blood circulatorily and cardiodynamically. A pneumatically-driven diaphragm type pump was implanted between the left ventricular apex and the descending aorta of a dog and was driven by ECG-synchronous counterpulsation method with heart rate versus pump beating number ratios of 1:1, 2:1 and 4:1 and fixed beating number method with beating number of 60 and 80 beats/min (bpm). In order to measure the left ventricular diameter and myocardial length, 7 pairs of ultrasonic sonomicrometers were embedded intra-left ventriculomurally. Ischemia was prepared by ligating the left anterior descending coronary artery (LAD). Bulk mechanical work and regional mechanical work were calculated from these dimensions and the left ventricular pressure. The following results were obtained: 1) In all driving modes but that of 4:1, compared with non-driven pumping, heart rate, peak left ventricular pressure, mean left atrial pressure and total peripheral resistance showed low values, and mean aortic pressure and total blood flow showed high values. Moreover, in the above driving modes, total bypass was obtained. 2) In the above driving modes, bulk and regional mechanical works were practically null with a de loading effect of 100% or so being obtained. 3) Compared with the left atrial dehematizing system, peak left ventricular pressure showed remarkably low value with increases in mean aortic pressure and total blood flow, and with remarkable decreases in bulk and regional mechanical works. 4) In driving modes of 2:1, 1:1, I60 and I80, little difference in the effect according to the driving mode was noted.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1427604 TI - [Effects of a non-ionic low osmolar contrast medium on thyroidal radioiodine uptake in rats]. AB - Recently non ionic low osmolar contrast media (NILOCM) have been widely used in radiographic contrast studies. These new agents have a great advantage over conventional ionic high osmolar contrast media (IHOCM) in low chemical toxicity and good X-ray absorption. However, their effects on thyroid function, especially on thyroidal radioiodine uptake (TRIU), are still unknown and it is not clear how long NILOCM interfere with TRIU. Therefore, the extent of the interference with TRIU caused by previous NILOCM injection was examined using rat thyroid. Male WKA rats were divided into four groups and fed under different dietary conditions, A) routine diet for rats; B) low iodine diet (LID) for 1 week, C) LID for 2 weeks, and D) LID for 8 weeks. Iopamidol was used as NILOCM, and iothalmate, one of IHOCM, was also employed for comparative study. After feeding, some rats in each group were injected with 300 mgI/kg. b.w. of iopamidol or iothalmate. The remaining rats in each group received saline injection as the control. At day 1, 2, 3, 7, and 14 following injection, I-131 was administered intravenously and a 24 hour TRIU (% dose/mg tissue) was measured in each group. Thyroidal iodine content (TIC: micrograms I/mg tissue) at day 1, 7, and 14 was also measured in group A, C, and D. Until day 3, severe suppression on TRIU was observed in all groups, and TIC elevated at day 1 in iothalmate-injected rats. In iopamidol injected rats, TRIU and TIC recovered after then, and reached the same levels as those in control rats until day 14 except for group D. However, TRIU was still significantly lower and TIC levels in group D was higher at day 14 in iothalmate injected rats. It is concluded that iopamidol has less effects on TRIU and TIC with a shorter period of recovery than iothalmate. This results maybe beneficial to the patients who were injected NILOCM prior to radioiodine scintigraphy. PMID- 1427605 TI - [A clinical study on non-verbal psychotherapy in childhood and adolescence: a proposed classification and psychopathological considerations]. AB - The author examined the therapeutic sequence of 37 child and adolescent cases of neurotic disorder in whom the non-verbal approach was successively taken for more than 6 months. The cases could be classified into two types, according to their choice of non-verbal methods: "simple type" cases, who chose only one method at all their therapeutic sessions and "mixed type" cases, who took various combinations of non-verbal methods during the period of psychotherapy. In "simple type" cases, premorbid character was usually introverted and emotionally stable. As for their family situations, their fathers were rather asthenic and their mothers often lacked emotional communication in child-rearing. Patients showed one or only few clinical symptoms. The therapeutic relationship with them was superficially calm and stable, and it was often difficult to deepen the emotional commitment further. In "mixed type" cases, on the other hand, premorbid character was emotionally often unstable. Their fathers tended to be away from home, and mothers were conspicuously overprotective and meddlesome. Their clinical symptoms were varied. In the therapeutic sessions, they often became dependent on therapists and, at the same time, ambivalent and unstable in certain conditions, showing dissatisfactions and reacting strongly against their therapists. The characteristics of these two types can be observed in relation to other clinical disorders. Regarding the development of interpersonal relationship and personality, it can be seen that the two types is derived from the different quality of the "sense of basic trust" of each patient acquired in early childhood. Based on the above findings, the author discussed a few psychopathological issues on his proposed classification. PMID- 1427606 TI - [Xenogenization of rat tumor cells by transfection with envelope gene derived from Friend murine leukemia virus]. AB - The highly tumorigenic rat hepatocellular carcinoma cell line cKDH-8-cl-11 was xenogenized by transfection with an envelope (FV-env) gene derived from Friend murine leukemia virus. The transfected tumor cells, expressing the FV-env gene product on the cell surface, were injected into normal and immunosuppressed (irradiated) syngeneic rats. All the irradiated rats developed tumors at the injection site. Thirteen out of fifteen normal rats rejected the xenogenized cells and acquired tumor transplantation resistance to the parent (nontransfected) cell line. The tumor cells that grew in normal rats failed to express th FV-env gene product during growth in vivo, but resumed expression during in vitro primary culture. These results suggest that the FV-engine product, when expressed on tumor cell surfaces, displays biological characteristics which are immunologically recognized by normal rats and induces tumor rejection. Moreover the results show that the FV-env gene product is a good candidate for the xenogenization of tumor cells. PMID- 1427607 TI - [Changes in magnesium and calcium levels in blood and stomach tissue of patients with stomach cancer]. AB - This study was performed to evaluate changes in Magnesium (Mg) and Calcium (Ca) levels in blood and cancerous stomach tissue of patients with stomach cancer, who were classified into four stages of malignancy and three groups of metastatic category. Mg and Ca were determined with atomic absorption spectrophotometer after blood and stomach tissue were digested with nitric and perchloric acid. Significantly high Mg levels in the early stages were found both in plasma and in whole blood. On the other hand, significantly low Ca levels were found in blood plasma in most stages and in all metastatic groups. By contrast, significantly high Ca levels were observed in whole blood in later malignant stages and in two metastatic groups. Significantly high Mg and low Ca levels were found in cancerous stomach tissue in patients with stomach cancer, as compared to their normal stomach tissue. The same tendencies were observed in each malignant stages and metastatic groups. These changes in Mg and Ca levels in blood and cancerous stomach tissue may reflect inherent peculiarities of stomach cancer. PMID- 1427608 TI - [A case of the panencephalopathic type of Creutzfeldt-Jakob disease with retinal involvement]. AB - Neuropathological study of the visual pathway from the retina to the occipital cortex in Creutzfeldt-Jakob disease (CJD) has been scarcely performed. In the present study, pathological involvement of the visual pathway was observed in a 54-year-old man with CJD. The patient had the onset of visual disturbances in December 1985. He subsequently developed progressive dementia, right hemiparesis, ataxia and dysarthria, and rapidly fell into decerebrate posture in February 1986. In March 1986, myoclonus appeared on the whole body and EEG revealed periodic synchronous discharges, while brain CT and CSF findings showed no abnormalities. Myoclonus was observed most frequently from May to October 1986, and then reduced gradually. Brain atrophy on CT started from April 1986, and was progressive till the end stage of the disease. He died in January 1988, and the total clinical course was about 24 months. Neuropathological examination revealed severe degeneration of the cerebral cortex and the white matter. In the cerebral cortex, marked loss of neurons, astrogliosis, and spongiform changes were observed. In the cerebral white matter, the destruction of myelin sheaths and axons were evident. The cerebellum showed prominent loss of granule cells. These findings are consistent with those of the panencephalopathic type of CJD. In the visual pathway, loss of ganglion cells and bipolar cells in the retina, mild demyelination of the optic nerve, neuronal loss in the lateral geniculate body, and severe degeneration in the visual cortex were observed. The present case suggests that the neuropathological investigation in the visual pathway from the retina to the occipital cortex is important for clarifying the pathological processes in the visual system in CJD. PMID- 1427609 TI - Delayed removal of 125I-labeled very low density lipoprotein from plasma of rats with insulin-deficient diabetes mellitus. AB - The present studies demonstrate that the removal rate of exogenously labelled 125I-VLDL-protein is prolonged when total serum from insulin-deficient rats combined with isolated 125I-VLDL is injected into normal recipient rats (6.8 +/- 0.7 vs 4.2 +/- 0.4 min; p < 0.01), but not when 125I-VLDL-protein is isolated and injected alone (4.2 +/- 0.8 vs 4.3 +/- 0.8 min). Furthermore, the present studies demonstrate that when isolated 125I-VLDL-protein is recombined with either VLDL free (d > 1.006 g/ml), or lipoprotein-free serum (d > 1.215 g/ml) from insulin deficient rats, the defect in removal rate of VLDL-protein observed in total serum is reestablished (125I-VLDL + VLDL-free serum from insulin-deficient rat vs that from normal rat: 7.6 +/- 1.2 vs 4.6 +/- 0.7 min, p < 0.05; and 125I-VLDL + lipoprotein-free serum from insulin-deficient rat vs that from normal rat: 6.4 +/ 0.7 vs 4.1 +/- 0.4 min, p < 0.01). These data suggest that a factor or factors exist in lipoprotein-free serum of insulin-deficient rats which interfere with the normal removal of 125I-VLDL. Since we have previously demonstrated a prolongation in the removal rate of endogenously labeled VLDL-3H-TG, the defect in removal of VLDL from the plasma of insulin-deficient rats appears to include both the lipid and protein moieties of the VLDL particles. PMID- 1427610 TI - Red cell membrane protein lateral mobility in diabetes mellitus. AB - In a group of 24 diabetics subdivided for type, we evaluated the red cell membrane protein lateral mobility marking intact red cells with pyrene-3 maleimide (3-PM) and calculating the dimer to monomer fluorescence intensity ratio (Iex/Im). The same fluorescent parameter was determined in a group of 13 normal controls. From the obtained data, it is evident that the red cell membrane protein lateral mobility clearly discriminates normals from diabetics of type 1 and 2. In normals and in diabetics of type 1 and 2 no relationship is present between this fluorescent determinant and the glycometabolic parameters (FBGL and HbA1c); considering all the diabetics, a negative relationship is evident between Iex/Im ratio and HbA1c only. PMID- 1427611 TI - Enzymatic glycosidase activities in experimental obesity. AB - Glycosidases are lysosomal enzymes that participate in the catabolism of glycoproteins and other glycoconjugates, and in some way may modify their activity in situations in which carbohydrate metabolism could be altered, such as the case of obesity. Using a fluorometric assay, a study was made of four glycosidase activities: N-acetyl-beta-D-hexosaminidase (NAG), alpha-mannosidase and alpha- and beta-glucosidase in the serum, pancreas, liver and kidney of 22 Zucker fa/fa genetically obese rats and of 23 fa/? controls, both with ages ranging between 13 and 15 weeks. After 12-14 hours fast and prior anaesthesia with sodium pentobarbital intraperitoneally, blood and the afore-mentioned organs were removed for enzymatic study of the serum and the organs after homogenization and centrifugation. In the serum a statistically significant increase in alpha mannosidase (p < 0.0001) and alpha-glucosidase (p < 0.02) activities was found in the fa/fa obese rats as compared with the controls. No statistically significant differences were found in serum hexosaminidase activity between the two groups, and no serum beta-glucosidase enzymatic activity was detected. In liver, a decrease was observed in hexosaminidase (p < 0.002) and alpha-glucosidase (p < 0.01) activities in the obese rats as compared with the controls. In whole pancreas an increase was found in alpha-glucosidase activity in the obese rats with respect to the controls (p < 0.001), with no statistically significant differences in the hexosaminidase, alpha-mannosidase and beta-glucosidase activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427612 TI - Analysis of nuclear 3,3',5-triiodothyronine receptor in the brown adipose tissue (BAT) of the postnatal lamb. AB - Postnatal thermogenesis in sheep is associated with increased sympathoadrenal activities, a T3 surge and an enhanced brown adipose tissue (BAT) type II 5' monodeiodinating (5'-MDI) activity. The latter peaks 3-4 days after birth and is known to be important in generating intracellular T3 for nuclear receptor binding. In order to further investigate the mechanism(s) responsible for neonatal thermogenesis, thyroid hormone nuclear receptor (T3NR) binding characteristics were quantified in lamb BAT from newborn (NB) to 30d of postnatal age. Maximal binding capacities (MBC, mean +/- SEM fmoles T3/mg DNA) in BAT showed a decrease as studied by ANOVA during the first 11 days (NB to 1d, 148 +/- 24 [N = 5, p < 0.01, cf. 3-5d group]; 3-5 d, 61 +/- 5.5 [N = 5]; 10-11d, 72 +/- 9.1 [N = 4]). Afterwards, MBC increased at 30d (196 +/- 32, N = 4, p less than 0.01, cf. 3-5d group). BAT T3NR binding affinities (10(9) M-1) were comparable in all age groups studied (NB-1d, 2.8 +/- 0.3; 3-5d, 3.4 +/- 0.3; 10-11d, 4.0 +/- 1.1; 30d, 2.4 +/- 0.4). The data suggest that the postnatal surge in T3 and type II 5'-MDI is accompanied with a concurrent decrease in MBC of BAT T3NR. The latter may represent a down-regulation of T3NR presumably in an attempt to regulate the overall effect of thyroid hormone in neonatal thermogenesis. PMID- 1427613 TI - Effect of insulin and adrenaline on the 59Fe transferrin uptake of lactating mouse mammary gland cells. AB - The results of insulin action (0.4 IU per mouse) are demonstrated in intact animals only. This action leads to a higher uptake of 59Fe. rabbit transferrin of isolated cells from lactating mouse mammary gland. It is suggested that most inactive transferrin receptors in the cell membrane are incorporated by the hormone action or some new receptors are synthesized. On the contrary, adrenaline in a dose 0.5 micrograms per animal demonstrated an opposite effect--a lower uptake of 59Fe. human transferrin from lactating mouse mammary gland. This is probably due to a redistribution of some part (about 28%) of the iron. Instead of flowing to the mammary gland it flows towards other organs for overcoming the stress situation. An alternative explanation could be the inhibition of endogenous insulin secretion by adrenaline. From our data it follows that insulin and adrenaline have an antagonistic effect on regulation of Fe transport in lactating mouse mammary gland. PMID- 1427614 TI - Differential effects of body weight, hyperinsulinemia and oral glucose load on serum C-peptide/insulin molar ratio. AB - Serum C-peptide immunoreactivity (CPR)/immunoreactive insulin (IRI) molar ratio was determined in 136 subjects without renal, hepatic and thyroid disorders, at fasting, and during the initial period of 75 g-oral glucose tolerance test. The subjects were divided into 4 groups based on their body weight and age; Group A, young (< 55 years) and normal body weight (body mass index [BMI, kg/m2] < or = 25) subjects; Group B, young and overweight (BMI > 25) subjects; Group C, aged (> or = 55 years) and normal body weight (BMI < or = 25) subjects; Group D, aged and overweight subjects. Fasting CPR/IRI ratio and absolute CPR level negatively correlated in Groups B and D but not in A and C. After oral glucose load with elevation of insulin, CPR/IRI ratio invariably declined in all groups and significant negative correlation between CPR/IRI and CPR was found in Groups A, B and D but not in C. Slope of the regression lines obtained for correlation between CPR/IRI ratio and CPR were significantly steeper at fasting compared to the post-stimulation phase. CPR/IRI ratio is affected by hyperinsulinemia and oral glucose load but not by obesity alone. Assuming that CPR/IRI ratio reflects hepatic extraction of insulin, the insulin clearance at fasting is progressively reduced with increasing insulin secretion in overweight subjects: failure to detect such phenomenon in normal body weight subjects may be due to a narrower CPR range in this population. Insulin metabolism at fasting and during glucose stimulation is likely to be regulated by distinct factors. PMID- 1427615 TI - Acute thyroid dysfunction (thyroiditis) after therapy with interleukin-2. AB - Interleukin-2 (IL-2) is frequently incorporated in antineoplastic therapy: While the effect of interferon on the thyroid has been extensively studied the impact of other cytokines on thyroid function is less well understood. We monitored the thyroid function in six patients who received IL-2 in combination with tumor necrosis factor-alpha (TNF) or alpha-Interferon (alpha IFN). Hyperthyroxinemia with suppressed TSH developed within the first four weeks of IL-2 administration; during this phase, there was no technetium or iodine uptake by the thyroid gland. During the following few weeks, serum thyroxine decreased and serum TSH rose, consistent with the development of primary hypothyroidism; during this phase, thyroidal isotope incorporation was normal. All hypothyroid patients received thyroxine replacement therapy upon documentation of hypothyroidism; in several cases thyroxine was successfully discontinued after 2-3 months. None of the patients had detectable antithyroidal antibodies and none experienced thyroid related pain, although two patients developed thyroid enlargement. We conclude that IL-2 administration is associated with the development of transient, subacute, painless thyroiditis. The frequency and severity of this complication requires further elucidation through systematic, prospective study. PMID- 1427616 TI - Serum procalcitonin as an index of inhalation injury in burns. AB - The molecular heterogeneity of serum immunoreactive calcitonin (iCT) was analyzed from a prospective study of 41 burn patients. Using different region-specific anticalcitonin antisera, the ratio of mid-region-recognizing to carboxyl terminal region-recognizing iCT was found to increase acutely in those who subsequently died. The highest ratios occurred in those who died early of respiratory complications. Sephadex chromatography and reversed-phase HPLC demonstrated that the serum iCT circulated predominantly in the large molecular mass prohormone form (16 kDa). In comparison, iCT of normal human lung and of normal thyroid was shown to consist primarily of smaller monomeric mass forms. Furthermore, in 12 normal volunteers who were evaluated with a calcium-pentagastrin infusion, the ratio of iCT levels did not differ from the baseline ratio despite a 50% increase in serum iCT. These results suggest that in burns, the inhalational injury associated hypercalcitonemia is characterized by a preferential release of procalcitonin; a form of constitutive secretion. The measurement of serum procalcitonin levels would appear to be a useful prognostic indicator of the severity of inhalational injury occurring in burn patients. PMID- 1427617 TI - A correlative study on serum cholylglycine levels in hepatobiliary disease. AB - The serum cholylglycine (CG), alanine aminotransferase (ALT) and total bilirubin levels were studied in 210 patients with hepatobiliary disease and in 70 healthy subjects. Serum CG concentrations in all the hepatobiliary diseases were found to be significantly higher than those of their controls. Patients with abnormal increases in ALT and bilirubin levels also showed raised CG concentrations; however, some patients with normal ALT and bilirubin levels, still had markedly elevated CG values. Patients with hepatic cirrhosis had high serum CG levels, followed, in descending order, by chronic active hepatitis and chronic persistent hepatitis. In the cholecystitis and cholelithiasis cases, their CG levels were significantly higher than those of the controls but lower than the values in hepatic disease patients; however, more cholecystitis cases had abnormally high serum bilirubin levels than CG. The results also show that serum CG concentrations vary in the different hepatobiliary diseases, and that serial CG measurements are more sensitive than measuring ALT and bilirubin levels in the diagnosis of hepatic diseases. Serum CG can be used as an index for evaluating the activity of chronic hepatitis; it can also be employed as a diagnostic tool in cholecystitis and cholelithiasis. PMID- 1427619 TI - Chronic control of cyclic AMP-dependent protein kinase of rat mammary gland. PMID- 1427618 TI - The participation of the activation of cAMP-dependent protein kinase in cytosolic acidification by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic osteosarcoma cells. PMID- 1427620 TI - Paradoxical inhibition of insulin release by D-glucose islets exposed to dopamine. PMID- 1427621 TI - Osmotic cell swelling stimulates receptor-mediated low density lipoprotein endocytosis and degradation. PMID- 1427622 TI - A role for thyroid hormone in the induction of ovulation and corpus luteum function. AB - We have previously demonstrated that thyroid hormone synergizes with follicle stimulating hormone (FSH) to exert stimulatory effects on granulosa cell differentiation and function, suggesting that it plays a physiological role in amplifying FSH-mediated differentiation of granulosa cells. The adequate differentiation of these cells, followed by normal follicle development, is indispensable for ovulation and subsequent corpus luteum formation. Thus, in the present studies, the clinical implications of thyroid hormone in the induction of ovulation and corpus luteum function were investigated. Serum levels of total 3,5,3'-triiodothyronine (T3) and total thyroxine (T4) as well as free T3 and T4 were significantly lower in patients with weight loss amenorrhea compared to normal cycling women. Although no ovulation was induced by clomiphene therapy when the serum T3 levels were less than 80 ng/dl, the rate of ovulation induced by clomiphene increased in parallel with the augmentation of serum T3 levels. This suggests that an adequate circulating level of thyroid hormone is one of the factors responsible for successful induction of ovulation by clomiphene citrate. Furthermore, the short luteal phase and insufficient progesterone secretion observed in patients with subclinical hypothyroxinemia were not improved by clomiphene therapy alone, but were improved markedly by combined treatment with thyroid hormone replacement and clomiphene citrate. These data imply that concomitant clomiphene treatment with thyroid hormone replacement therapy is of a great value not only for ovulation induction, but also for the treatment of luteal-phase defect in patients with subclinical hypothyroxinemia. PMID- 1427623 TI - Possible involvement of lipoxygenase products in human corpora lutea. AB - The present study was undertaken to determine the ability of cultured luteal cells from human corpora lutea to secrete progesterone (P4) and prostaglandins (PGs), and to assess the effects of the products of the lipoxygenase pathway on luteal P4 production. Luteal cells responded to human chorionic gonadotropin (hCG) with a significant increase (2- to 7-fold) in P4 production. Arachidonic acid significantly stimulated PGE2 synthesis by luteal cells in a dose-dependent manner. Both basal PGE2 production and the responsiveness to arachidonic acid were maintained for 8 days. In contrast, both PGF2 alpha and 6-keto-PGF1 alpha production abruptly declined as the culture proceeded. However, the addition of hCG did not further stimulate the accumulation of the 3 PGs assayed. In the subsequent experiment, 5-hydroxyeicosatetraenoic acid (5-HETE) and the reaction products of soybean lipoxidase of arachidonic acid (AA-LIP) were utilized for evaluating the involvement of the lipoxygenase pathway in luteolysis. The addition of 5-HETE dose-dependently inhibited P4 production by the cultured luteal cells. Although treatment with either arachidonic acid or lipoxidase alone had no effect on P4 production, AA-LIP significantly reduced P4 production in the presence or absence of hCG. These results suggest that the products of the lipoxygenase as well as of the cyclo-oxygenase pathway may be important in regulating the life span and function of human corpora lutea. PMID- 1427624 TI - Modulation of progesterone secretion by androgens in porcine granulosa cell cultures. AB - The influence of testosterone, androstenedione and dihydrotestosterone (DHT) on the progesterone (P4) production by cultured porcine granulosa cells was studied in the presence or absence of gonadotropins. Porcine granulosa cells from large follicles (6-12 mm in diameter) were incubated for 2 days with 5% CO2 in air with testosterone, androstenedione and DHT (10(-12), 10(-10), 10(-8) and 10(-6) M) in the presence or absence of luteinizing hormone (LH, 10 ng/ml) or follicle stimulating hormone (FSH, 30 ng/ml). P4 and pregnenolone (P5) in conditioned culture media were quantified by their specific RIAs. In the absence of gonadotropins, P4 in media with androgens were not significantly different from controls. In the presence of LH, the addition of testosterone (10(-10), 10(-8) M), androstenedione (10(-8) M) and DHT (10(-8) M) caused a significant 1.3- to 2.3-fold increase in P4 over that caused by LH alone. In contrast, in the presence of FSH, testosterone (10(-12), 10(-10) M), androstenedione (10(-12)-10( 6) M) and DHT (10(-6) M) reduced the levels of P4 by 22% to 41%. The addition of androgens with LH caused a significant increase in P5, while P5 decreased in the presence of FSH. P4/P5 ratios remained unchanged in the presence of both LH and FSH. These data suggest that the P4 production by cultured porcine granulosa cells is modulated in a paracrine or an autocrine fashion by androgens in the presence of gonadotropins, and that androgens may exert their actions partly by altering the activity of cholesterol side chain cleavage enzymes. PMID- 1427625 TI - New aspects of the physiology and pathology of the luteal phase: an overview. PMID- 1427626 TI - Sporadic appearance of luteal-phase defect in prospective assessment. AB - We studied the sporadic appearance of luteal-phase defect in the prospective assessment of consecutive cycles. Basal body temperature (BBT) was recorded in 36 women (20-35 years of age) for at least 3 consecutive cycles (total of 194 cycles). These BBT records were analyzed for pattern and luteal-phase length (LPL). Furthermore, the relationship was investigated between the BBT and luteal function in terms of serum hormonal levels and endometrial dating in the luteal phase. The length of the transitional period from the hypothermic to the hyperthermic phase was also studied in relation to luteal function in 59 women (21-33 years of age). The results were as follows: (1) Different BBT patterns and LPLs in consecutive cycles occurred in 36 and 67% of the observed cycles, respectively. (2) Cycles with abnormal steroid levels and endometrial dating were observed sporadically. (3) The length of the transitional period appeared useful for prospective evaluation of luteal function. These findings suggest that the conditions of the luteal function do not appear in every cycle of each woman. Therefore, assessing the function of one cycle seems of little use in predicting the function of the next or future cycles. PMID- 1427627 TI - Association of immunoreactive-inhibin levels with luteal function. AB - To evaluate immunoreactive (IR) inhibin as a marker of corpus luteal function, 134 women with natural ovulatory cycles were studied. Serum IR-inhibin levels during the luteal phase were significantly lower in women with low progesterone (P4) levels (less than 10 ng/ml). Endometrial dating correlated more with serum P4 than IR-inhibin levels. All 14 conceiving cycles showed serum P4 levels greater than or equal to 10 ng/ml and IR-inhibin levels greater than or equal to 3.67 IU/ml during the midluteal phase. Furthermore, IR-inhibin levels in the early follicular phase seemed to be associated with lowered P4 levels in the ensuing luteal phase. These results suggest that IR inhibin may be closely related to corpus luteum function. PMID- 1427628 TI - Analysis of clinical backgrounds and pathogenesis of luteal-phase defect. AB - To elucidate the clinical background of the luteal-phase defect (LPD), 201 LPD cycles were studied in 753 infertile women. One hundred and twenty-one cases (62.2%) of LPD showed transient hyperprolactinemia. In transient hyperprolactinemia, there was a significant inverse correlation between serum prolactin (PRL) 30 min after the 500-micrograms intravenous loading of thyrotropin-releasing hormone TRH (PRL30) and progesterone (P4) in the luteal phase (r = -0.67, p less than 0.005). Mature follicles (diameter greater than 20 mm as determined by ultrasonography) were observed in 74 cases (61.2% of the transient hyperprolactinemia cases). On the contrary, in 25 (12.4%) of the 121 LPD cases who showed the hyper-luteinizing hormone (LH) syndrome (LH/FSH ratio greater than 1), only 9 (36%) had mature follicles. Of the remaining 55 cases who showed neither transient hyperprolactinemia nor the hyper-LH syndrome, 27 cases (49.1%) had mature follicles. Five of these patients indicated a significantly higher LH pulse amplitude despite depressed P4 secretion in the luteal phase. From these results, it was concluded that the most common cause of LPD was transient hyperprolactinemia. The second cause of LPD was suspected to be disturbed follicle development due to the inappropriate ratio of LH/FSH in the hyper-LH syndrome. Another cause was speculated to be the primary failure of a response from the corpus luteum to LH. Treatments based on the conclusions mentioned above resulted in a 48.3% pregnancy success rate. PMID- 1427629 TI - Hysteroscopic assessment of midsecretory-phase endometrium, with special reference to the luteal-phase defect. AB - To investigate the functional aspects of secretory-phase endometrium, hysteroscopy was performed in 61 patients for in vitro fertilization-embryo transfer (IVF-ET), and 50 women for infertility evaluation. All women had normal ovulatory cycles. The hysteroscopic assessment of secretory-phase endometrium was made by characterizing the glandular openings (GO) and vasculature. The assessments were classified as 'good': characterized by ring-type GO and well developed vessels; and 'poor': characterized by dot and/or punctate-type GO and fine vasculature. In the 30 patients classified 'good' prior to the IVF cycle, there was a higher pregnancy rate (40%) than in 'poor' ones (13%). Thirty of 50 infertile women were classified 'good', and their average age was lower than that of the remaining 20 in the 'poor' group. Preovulatory estradiol was significantly higher in the 'good' than in the 'poor' group. From an analysis of 20 patients with a 'poor' assessment, it was demonstrated that the maturation of secretory phase endometrium was affected by a failure of folliculogenesis, progesterone secretion, endometrial growth and menstrual shedding. PMID- 1427630 TI - Clinical importance of endometrial histology and progesterone level assessment in luteal-phase defect. AB - In order to clarify the relationship between endometrial histology and progesterone (P4), plasma P4 and estradiol levels in the luteal phase were measured in 126 cases of unexplained infertility. Endometrial biopsies were performed in the midluteal period of menstrual cycles. Forty-three of the 126 cases showed retarded endometrium. Of these 43 cases, 23 exhibited three different types of abnormal P4 secretion. Type A showed low P4 levels throughout the luteal period. Type B showed low P4 levels only in the early luteal period. Type C showed normal P4 levels in the early luteal period followed by a prompt decline. These findings indicated that P4 determination during the early, mid- and late luteal phases is necessary to assess P4 secretion. However, 20 of the 43 cases had normal P4 levels through the entire luteal phase, demonstrating an insufficient response of the endometrium to P4. Consequently, histological examination of the endometrium is required to investigate the luteal phase defect. PMID- 1427631 TI - Influence of progesterone/estradiol ratio on luteal function for achieving pregnancy in gonadotropin therapy. AB - The purpose of this study was to evaluate the influence of the relationship between plasma progesterone (P4) and estradiol (E2) levels in the luteal phase for achieving pregnancy in human menopausal gonadotropin (hMG)-human chorionic gonadotropin (hCG)-treated cycles. Plasma P4 and E2 levels were determined in 93 hMG-hCG-treated cycles (23 pregnant and 70 nonpregnant) of 46 patients during 3 periods of the luteal phase, using radioimmunoassay. In addition, 88 spontaneous ovulatory cycles and 100 clomiphene-treated cycles were also studied in the same manner. In hMG-hCG-treated cycles in the early luteal phase, the P4/E2 ratio in pregnant cycles was significantly higher than that in nonpregnant cycles. There was no significant difference between the P4/E2 ratios of the luteal phase of hMG hCG-treated pregnant-group, clomiphene-treated and spontaneous ovulatory cycles. In nonpregnant cycles, however, the P4/E2 ratio in hMG-hCG-treated cycles was significantly lower than that in clomiphene-treated or spontaneous ovulatory cycles. These results suggest that in hMG-hCG-treated cycles, the P4/E2 ratio may be a more reliable index of luteal function for achieving pregnancy than P4 levels alone. PMID- 1427632 TI - Factors promoting embryo implantation in in vitro fertilization and embryo transfer. AB - The low implantation rate after embryo transfer (ET) is the most important problem to be solved in in vitro fertilization and embryo transfer (IVF-ET). Various factors which may affect embryo implantation in the endometrium have been examined. In this study, the influence of the timing of luteinization on the establishment of pregnancy was investigated. Follicle stimulation was performed by luteinizing hormone-releasing hormone agonist, human menopausal gonadotropin and human chorionic gonadotropin (hCG). hCG was injected on the day when the mean diameter of two follicles exceeded 16 mm, and 36 h after the injection the oocyte was retrieved. Progesterone (P4) supplement was started on the day of ovum retrieval (50 mg), followed by 30 mg for 14 days. The patients were divided into three groups: (1) the pregnant patients (n = 20: group Pre); (2) the nonpregnant patients without bleeding during P4 injection (n = 35; group N), and (3) the nonpregnant patients with bleeding during P4 injection (n = 30; group B). The number of follicles that developed, endometrial thickness, the day of operation, the number of oocytes harvested, the number of good quality oocytes, the number of oocytes fertilized, the number of embryos transferred, estradiol (E2) and P4 levels, and the E2/P4 ratio were examined. The endometrial thickness of group Pre (10.9 +/- 0.6 mm; mean +/- SEM) on the day of hCG injection was significantly (p less than 0.05) greater than that of groups N (9.0 +/- 0.4 mm) and B (9.2 +/- 0.3 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427633 TI - Further observations on serial serum immunoreactive inhibin levels in the luteal phase and early gestation after ovarian stimulation for in vitro fertilization and embryo transfer. AB - Serum immunoreactive inhibin of the luteal phase was measured by radioimmunoassay in 71 patients in vitro fertilization and embryo transfer (IVF-ET). The correlation between the pregnancy outcome and the serial inhibin pattern from the luteal phase to early gestation was studied. In nonconception cycles (n = 35), serum inhibin concentration rose and reached a peak level around 5 or 6 days after oocyte pick-up (OPU), then fell to the level of the early follicular phase. In conception cycles (n = 22), serum inhibin levels rose again 10-15 days after OPU. Serum inhibin levels were significantly higher from 10 days after OPU in multiple pregnancy (n = 5) than in single pregnancy (n = 17). In viable single pregnancy (n = 17), serum inhibin levels were significantly higher than in non viable pregnancy (n = 14) from 15 days after OPU. Serum inhibin levels in early gestation correlated well with the pregnancy outcome of IVF-ET. These data suggest that inhibin is an important factor for the diagnosis of pregnancy outcome. PMID- 1427634 TI - Role of corpus luteum function in embryo implantation. AB - The present study was undertaken to evaluate the role of corpus luteum function in the implantation process of cryopreserved embryos. Six patients with tubal infertility were studied, with a total of 27 fresh embryos being replaced following controlled ovarian hyperstimulation and in vitro fertilization. These embryo transfers failed to produce pregnancy. From the patients, 22 supernumerary embryos were cryopreserved and 10 viable frozen-thawed embryos were transferred in a subsequent natural cycle, resulting in 2 pregnancies. In 1 of the pregnancies, the serum concentrations of estradiol (E2) and progesterone (P4) in the midluteal phase were 29 pg/ml and 5.6 ng/ml, respectively. These values were considered to be below the physiological range. These data suggest that a pregnancy can be achieved in spite of low circulating E2 and P4 levels during the luteal phase, which are generally indicative of the luteal phase defect. PMID- 1427635 TI - Day-night rhythm disturbance, pineal function and human disease. AB - Depression, mania and probably starvation all induce changes in pineal function. At present it is unknown what secondary effects on the endocrine and other systems are produced by these changes. Studies in rats have established an entraining effect of melatonin on locomotor activity and a feedback effect on the pineal itself. Studies of jet-lag and of sleep dysregulation in a blind subject established that melatonin treatment has a synchronizing effect in these conditions. Further investigations will be necessary to establish whether melatonin reduction in depression and other disorders leads secondarily to dysregulation of other circadian rhythms. PMID- 1427636 TI - Gonadotropin regulation, oestrogens and the immune system. AB - Several transmitters and neuropeptides participate in the regulation of gonadotropins. At the hypothalamic level, control of gonadotropin releasing hormone (GnRH) involves noradrenaline, GABA, glutamate, angiotensin II, neuropeptide Y, neurotensin, and 5-hydroxytryptamine as well as interleukins 1 and 2. Ovarian steroids can interfere with gonadotropin regulation by either direct effects on GnRH release or by increasing the sensitivity of anterior pituitary cells to GnRH, thus potentiating the release of pituitary hormones. These interactions involve discrete actions on second messenger systems; similar processes also account for brain and endocrine effects on immune cells. PMID- 1427637 TI - Neurohypophyseal peptides and psychopathology. AB - The study of neurohypophyseal peptides in various neuropsychiatric disorders is of interest because the hypothalamo-posterior pituitary axis is directly influenced by modifications of central neurotransmitter metabolism involved in behaviour control. Moreover, the main neurohypophyseal peptides, namely vasopressin and oxytocin, are themselves capable of modifying behaviour. In this paper the author discusses current understanding of the anatomy and physiology of the main central vasopressinergic and oxytocinergic pathways, followed by a description of the principal actions of exogenously administered vasopressin and oxytocin on human behaviour. Finally, modification of endogenous neurohypophyseal function encountered in different pathological states are described. PMID- 1427638 TI - Genetic disorders of adrenal hormone synthesis. AB - Steroid 21-hydroxylase is the enzyme involved in 90-95% of cases of congenital adrenal hyperplasia (CAH). The general feature of CAH, which results from an enzymatic block at any stage in the synthesis of cortisol, is increased serum adrenocorticotropin and thus stimulated adrenal synthesis of steroids proximal to the block. All enzyme defects causing CAH are autosomal recessive traits. The early steps in cortisol synthesis are common to adrenal and gonadal steroid pathways, thus CAH caused by dysfunction of the enzymes supporting these steps is also characterized by insufficient production of gonadal hormones, causing impaired genital development in the genetic male. The absence of or severe reduction of steroid 21-hydroxylase activity also causes prenatal hypersecretion of androgens by the adrenal cortex, which results in external genital ambiguity in genetic females. This paper discusses the classical and nonclassical forms of CAH, their aetiology, diagnosis and treatment, and also describes recent advances in prenatal diagnosis and treatment which avoids the need for corrective genital plastic surgery in infancy. PMID- 1427639 TI - The experience of neonatal screening for congenital adrenal hyperplasia. PMID- 1427640 TI - Adrenal disorders and polycystic ovary syndrome. AB - Adrenal hyperandrogenism is a common feature of polycystic ovary syndrome (PCO). It is controversial whether the noncongenital adrenal hyperplasia disorders represent some sort of primary defect within the adrenal gland or are secondary to the effects of the abnormal hormonal milieu on adrenal enzyme activity, either the high androgen or luteinizing hormone levels. Adrenal androgens, both directly and by their aromatization to oestrogens, can cause the clinical and biochemical syndrome of PCO. PMID- 1427641 TI - Evaluation of young women with congenital adrenal hyperplasia: a pilot study. AB - To evaluate the outcome of medical and surgical treatment of 10 young women with congenital adrenal hyperplasia (CAH), final height, weight, body proportions and body hair growth as well as aspect and functionality of the external genitalia were assessed. The final height was below-2 SD of the target height in 55%, though the body proportions were in the normal range. Only 3 patients were menstruating regularly. Scores for 'hormonal' body hair growth were in a higher range. Gynaecological examination revealed that in 5 out of 9 patients, the genitalia were functionally acceptable. This pilot study stresses that from birth into adulthood of female patients with CAH there is a need for a combined therapeutic approach by a paediatric endocrinologist, a surgeon and a psychologist. This will improve the physical and psychosocial well-being of these patients. PMID- 1427642 TI - Congenital anorchia: natural history and treatment. AB - This paper discusses the definition, pathogenesis, diagnosis and treatment of congenital anorchia. It concludes that preparations containing esters of testosterone are preferable to synthetic derivatives for long-term treatment as they are metabolized in the same way as endogenous testosterone. In addition, it appears that recommended doses for replacement therapy are lower than previously suggested. An ideal formulation of testosterone for use in androgen replacement therapy is not currently available. PMID- 1427643 TI - Physical and mental development of adolescent males with Klinefelter syndrome. AB - Of 25,000 Danish schoolboys, aged 15-16 years, 16 were found to have previously undiagnosed Klinefelter's syndrome. Comparison of these boys with normal controls indicated that on average these subjects had increased height, reduced weight, impaired hearing, slightly lowered intelligence, poor school performance, increased incidence of psychological consultation and lowered sexual activity compared with their peers. PMID- 1427644 TI - Hypogonadotropic hypogonadism; the genetic defect. A hypothesis based on human and animal prototypes. AB - X-linked hypogonadotropic hypogonadism (HH) in humans may involve the genes responsible for the development and migration of GnRH neurons from the olfactory placode to the hypothalamus. The evidence for this includes the lack of hyperprolactinaemia in cases of X-linked HH, the associated abnormalities in the context of contiguous gene syndromes involving Xp deletions, and pertinent anatomical findings. The genetic defect in human HH appears, therefore, to be different from that found in the hpg mouse model. PMID- 1427645 TI - Clinical data regarding the growth of diabetic children. AB - Many authors have reported retarded growth in children with diabetes, though this has been a somewhat variable finding. However, with the newer treatment regimens for diabetes the problem of reduced growth rates has largely been solved. PMID- 1427646 TI - Insulin and growth factors adaptation to normal puberty. AB - Insulin and IGF-1 production were measured throughout childhood and puberty and into adult life. Basal insulin and IGF-1 secretion increased during puberty, falling back to prepubertal levels in adulthood. However, fasting glucose levels remained constant, implying an increase in tissue resistance to insulin coinciding with puberty. PMID- 1427647 TI - The GH-transgenic mouse as an experimental model for growth research: clinical and pathological studies. AB - The objectives and the methodology of mammalian gene transfer are discussed and findings in growth hormone (GH) transgenic mice are reported to illustrate the potential offered by genetically designed animal models for investigations in various areas of biomedical research. Transgenic mice expressing hybrid genes composed of either human or bovine GH coding sequences fused to the mouse metallothionein I promoter show high serum levels of heterologous GH, increased growth rates and final adult size, decreased life expectancy and a variety of pathological changes. PMID- 1427648 TI - Growth hormone gene regulation by trans-acting factors. AB - The promoter sequence of the growth hormone (GH) gene binds the ubiquitous factors nuclear factor 1, activator protein-2, upstream stimulatory factor and Sp1. A pituitary-specific factor known as growth hormone factor 1 or Pit-1 also binds to the promoter sequence. This factor is responsible for somatotroph specific expression of GH. It is also involved in the effect of GH-releasing hormone and in the ontogeny of the anterior pituitary. PMID- 1427649 TI - Biological rhythms in reproductive processes. AB - Biological rhythms play an important role in the regulation of many different physiological systems, including the reproductive system. The 24-hour clock system plays a role in regulating the production, release, synthesis and action of reproductive hormones and in the timing of critical events in the ovarian cycle. Research into the importance of biological rhythms on human reproduction is just beginning, future work is likely to reveal new and unexpected ways in which these rhythms affect human reproduction. PMID- 1427650 TI - Perinatal development of day-night rhythms in humans. AB - Evidence suggests that the suprachiasmatic nuclei function as a circadian pacemaker in humans. The development of the circadian timing systems may be similar to that described in rodents and nonhuman primates. Awareness of circadian rhythmicity during development should improve infant care and increase the understanding of several disease states. PMID- 1427651 TI - Hepatitis C virus infection in medical personnel after needlestick accident. AB - Hepatitis C virus infections in medical personnel after needlestick accidents have been documented generally by detection of seroconversion to a hepatitis C virus nonstructural region antigen, c100-3 (a marker of infection). We tested for hepatitis C virus core-derived antibodies and genomic RNA in addition to c100-3 antibody in 159 cases of needlestick exposure that did not involve patients positive for HBsAg. Of these we found 68 cases with index patients positive for both hepatitis C virus RNA and antibodies and members negative for antibodies to HCV core or c100-3 before the needlestick accidents. Seven of these medical personnel became infected with hepatitis C virus after the accidents. Their hepatitis was generally subclinical or self-limited and transient, except for one patient in whom liver enzyme elevation persisted along with the antibodies. In our study, the risk of hepatitis C virus transmission from a single needlestick accident with hepatitis C virus RNA-positive blood was 10%, considerably higher than the 4% estimated in a previous study. We found that donor blood with antibody to an hepatitis C virus core-derived peptide with enzyme-linked immunosorbent assay optical densities greater than 2.0 carried a significant risk of transmitting hepatitis C virus to needlestick victims. No hepatitis C virus seroconversions occurred in medical personnel exposed to hepatitis C virus antibody-negative or hepatitis C virus RNA-negative blood; however, one such exposure resulted in a very mild non-A, non-B, non-C hepatitis. PMID- 1427652 TI - Therapy for chronic hepatitis B with lymphoblastoid interferon-alpha and levamisole. AB - About one third of patients with chronic hepatitis B show a sustained response when treated with interferon-alpha. Combining interferon-alpha with immunomodulators might be a way to increase response rate. The aim of this study was to compare the efficacy of lymphoblastoid interferon-alpha given alone with its efficacy when combined with levamisole in chronic hepatitis B. Forty-five patients with HBeAg-positive chronic hepatitis were randomly selected (with stratification for ALT levels) to receive a 6-mo course of combination therapy with lymphoblastoid interferon-alpha (5 million units/m2 three times per week) and levamisole (150 mg three times per week) or lymphoblastoid interferon at the same dose regimen and a matching placebo. Final evaluation 18 mo after randomization revealed a loss of both HBeAg and hepatitis B virus DNA with ALT normalization in 38% of patients treated with interferon-alpha alone and in 10% of patients receiving combination therapy. The higher response rate observed in patients treated with interferon-alpha alone was maintained after stratification for basal ALT levels (i.e., higher [45% vs. 10%] or lower [31% vs. 9%] than three times the upper normal value). The length of time to sustained HBeAg clearance was significantly (p < 0.05) shorter in patients receiving monotherapy than in patients receiving combination therapy. Blinded histological assessment revealed improvement in 44% of patients treated with interferon-alpha alone compared with improvement in 6% of patients receiving combination therapy. These results indicate that levamisole has no additive effects when combined with interferon alpha in the treatment of HBeAg-positive chronic hepatitis. PMID- 1427653 TI - Expression and localization of the small and large delta antigens during the replication cycle of hepatitis D virus. AB - To study the expression and localization of delta antigen during the replication cycle of hepatitis D virus, we cotransfected HuH-7 hepatoma cells with a hepatitis B virus expression plasmid and plasmids expressing the small or large delta antigen or the entire HDV genome. The transfected cells and culture medium were analyzed on double immunofluorescence staining for delta antigen and HBsAg, on Western blotting and on Northern-blot hybridization from 4 hr to 9 days after transfection. In cells transfected with the expression plasmid carrying the small delta antigen open reading frame, only the small delta antigen was expressed; it was localized in the nucleolus and was not released into the medium during the culture period. In cells transfected with the large delta antigen expression plasmid, the large delta antigen expressed was localized in the nucleolus at the initial stage; this was followed by relocalization in nucleoplasm. Finally, large delta antigen was released in HBsAg-enveloped particles within 1 day of transfection. In cells cotransfected with hepatitis B virus and hepatitis D virus expression plasmids, the small delta antigen was expressed 4 hr after transfection, whereas the large form was expressed 3 days after transfection. Expression of the large delta antigen coincided with the localization changes from nucleolar to mixed stage and, finally, to nucleoplasm and release of the hepatitis D virus particles. The large delta antigen appears to play a key role in relocalization of the delta antigen and packaging of the hepatitis D virus virions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427654 TI - Emergency liver transplantation for fulminant liver failure in infants and children. AB - We report our results with orthotopic liver transplantation in children with fulminant liver failure. Thirty-five children with fulminant liver failure were evaluated for liver transplantation. The main causes of liver failure were viral hepatitis (54.2%), drug-induced liver injury (14.2%) and Wilson's disease (11.4%). Children were considered as candidates for liver transplantation only if hepatic encephalopathy was associated with a decrease in the level of factor V to below 25%. Seven children (20%) did not meet this criterion and recovered spontaneously. Six children (17.1%) had contraindications for liver transplantation and died. In three of these six children, contraindications included irreversible brain damage at the time of admission. Twenty-two children (62.8%) met the criteria for liver transplantation and were placed on the emergency transplant list. Three of them died awaiting grafts. Nineteen children underwent liver transplantation; 13 of them (68.4%) are alive without sequelae, after 6 mo to 4 yr of follow-up, at this writing. Four of the children who died after surgery had severe encephalopathy on admission that did not improve after liver transplantation. In conclusion, emergency liver transplantation appears to be an effective treatment for children with fulminant liver failure. Nevertheless, irreversible brain damage developed in 10 patients, and they died before or after surgery. We postulate that many of these deaths could have been avoided if children had been transferred to a liver transplantation facility and had undergone transplantation earlier. We emphasize that children with acute liver failure should be transferred to a center that performs liver transplantation before the development of hepatic encephalopathy. PMID- 1427655 TI - Human cholecystitis is associated with increased gallbladder prostaglandin I2 and prostaglandin E2 synthesis. AB - Microsomal prostanoid synthesis was compared in normal gallbladders removed during organ donation and inflamed gallbladders removed at cholecystectomy. Normal human gallbladder microsomes demonstrated low rates of conversion of [14C]arachidonic acid to total labeled prostanoids, which increased during 1 to 30 min of incubation. Normal human gallbladder microsomes converted labeled substrate to all primary prostaglandins without demonstration of a major product. Inflamed human gallbladder microsomes increased the rate of conversion of [14C]arachidonic acid to total labeled prostanoids two or three times over the levels demonstrated by normal gallbladder microsomes at all times of incubation (p < 0.01). The main prostanoids synthesized by the inflamed human gallbladder microsomes were prostaglandin E2 and 6-keto-prostaglandin F1 alpha, which were increased four times over the levels demonstrated by normal gallbladder microsomes (p < 0.01). These data showed that inflammation of the human gallbladder was associated with increased synthesis of gallbladder 6-keto prostaglandin F1 alpha and prostaglandin E2. PMID- 1427656 TI - Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study. AB - The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension. PMID- 1427657 TI - Characterization of sodium-dependent amino acid transport activity during liver regeneration. AB - Liver regeneration occurs after removal of or damage to a portion of the liver; it leads to restoration of the original liver mass. The activities of three sodium-dependent amino acid transporters--system A, system N and system ASC--were determined during a 5-day period of liver regeneration in the rat. Seventy percent hepatectomy or laparotomy was performed in pairs of rats; these rats' livers were removed at different time points after surgery. Transport activity was determined through measurement of the Na(+)-dependent uptake of tritiated amino acids by isolated hepatic plasma membrane vesicles. System A activity, as measured by the Na(+)-dependent uptake of 2-aminoisobutyric acid, is increased in the regenerating liver 2 to 24 hr after surgery compared with that of controls. Kinetic analysis of 2-(methylamino)isobutyric acid uptake showed a 100% increase in the maximum velocity of system A transport in the hepatectomized animals with no change in the Michaelis constant, suggesting an increase in the number of system A transport proteins in the plasma membrane of regenerating liver. During liver regeneration, no changes were noted in the transport activities of system N and system ASC as measured by the uptake of glutamine and cysteine, respectively, in the presence of 2-(methylamino)isobutyric acid. Our work suggests that system A performs a unique role in the secondary active transport of its substrate neutral amino acids to meet the metabolic demands of regenerating liver. PMID- 1427658 TI - The incidence of portal vein thrombosis at liver transplantation. AB - The incidence of portal vein thrombosis was examined in 885 patients who received orthotopic liver transplantations for various end-stage liver diseases between 1989 and 1990. The thrombosis was classified into four grades. Grade 1 was thrombosis of intrahepatic portal vein branches, grade 2 was thrombosis of the right or left portal branch or at the bifurcation, grade 3 was partial obstruction of the portal vein trunk, and grade 4 was complete obstruction of the portal vein trunk. Among the 849 patients without previous portosystemic shunt, 14 patients (1.6%) had grade 1, 27 patients (3.2%) had grade 2, 27 patients (3.2%) had grade 3 and 49 patients (5.8%) had grade 4 portal vein thrombosis. The incidence of portal vein thrombosis was highest (34.8%) in the patients with hepatic malignancy in the cirrhotic liver, followed by those with Budd-Chiari syndrome (22.2%) and postnecrotic cirrhosis of various causes (15.7%). The patients with encephalopathy, ascites, variceal bleeding, previous splenectomy and small liver had significantly higher incidences of portal vein thrombosis than the others. The total incidence of portal vein thrombosis among the 36 patients with previous portosystemic shunt was 38.9%, which was significantly higher than that (13.8%) of those without shunt. PMID- 1427659 TI - Failure of simple biochemical indexes to reliably differentiate fulminant Wilson's disease from other causes of fulminant liver failure. AB - Serum, urine and tissue biochemical findings were studied in 21 cases of fulminant Wilson's disease with respect to the value of a recently described biochemical index based on serum alkaline phosphatase and total serum bilirubin levels, and these cases were compared with 193 other cases of fulminant liver failure. Serum bilirubin, alkaline phosphatase and AST levels found in fulminant Wilson's disease were significantly different from those found in other cases of fulminant liver failure, but differentiation from other causes of fulminant liver failure on the basis of these biochemical parameters was not possible. The alkaline phosphatase/bilirubin and aspartate AST/bilirubin ratios derived from the above parameters were also significantly lower in fulminant Wilson's disease than in other categories of fulminant liver failure, but distinction between diagnostic categories on this basis was not possible. When ratios that correctly identified all cases of fulminant Wilson's disease were selected, 59/190 (31%) and 84/190 (44%) cases of non-Wilsonian fulminant liver failure would erroneously be assigned a diagnosis of fulminant Wilson's disease, by alkaline phosphatase/bilirubin and AST/bilirubin ratios, respectively. A low alkaline phosphatase-to-bilirubin ratio (< 0.57) in any category of fulminant liver failure suggested a significantly worse prognosis than in cases with higher ratios (chi 2, Yates' corrected = 5.37, p = 0.02). In the Wilson's disease group, serum and hepatic copper and ceruloplasmin concentrations were normal in 4/21, 2/15 and 2/19, respectively, whereas urinary copper level was elevated in 18/18 and was the most valuable test in diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427660 TI - Sequential appearance of intestinal mucosal cell types in the right and caudate liver lobes of furan-treated rats. AB - Furan rapidly induces in rat liver a unique, lobe-specific pattern of development of intestinal metaplasia and associated cholangiofibrosis. To establish early cell-precursor relationships in the genesis of this cholangiofibrosis, a time course study was conducted in which young adult male Fisher 344 rats received furan by gavage at a daily dose of 45 mg/kg body wt over a 32-day treatment period. An analysis of individual liver lobes obtained at different time points from these animals during furan treatment revealed the following sequence of histopathological changes, which were located mainly in the right and, to a lesser extent, the caudate liver lobes: day 1, severe hepatonecrosis in zone 3 extending into zone 2 of the liver acini; days 3 to 5, presence of a diffuse inflammatory cell infiltrate in hepatonecrotic areas, which gradually resolved; day 7, prominent bile ductule hyperplasia in tissue sections exhibiting marked loss of normal liver parenchyma; day 9, continued replacement of injured liver by hyperplastic bile ductule tissue, which now contained occasional metaplastic glandular structures composed of columnar basophilic epithelial cells; days 12 to 16, increasing cell diversity in the developing metaplastic glands, with the sequential appearance of goblet cells, Paneth cells and serotonin-positive neuroendocrine cells; and day 32, typical cholangiofibrosis defined by hyperplastic bile ductule-type structures in association with an increased number of metaplastic intestinal glands and progressively more dense fibrotic stroma. Interestingly, at 16 and 32 days the cellular composition of the newly formed metaplastic intestinal glands in liver closely resembled that of the crypts of Lieberkuhn in the normal adult rat small intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427661 TI - Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo. AB - Hepatocyte growth factor, a potent mitogen for mature hepatocytes in vitro, seems to function as a hepatotrophic factor for liver regeneration. We examined the mitogenic effect of hepatocyte growth factor on mouse liver in vivo. The labeling index of hepatocytes was markedly increased when recombinant human hepatocyte growth factor was injected intravenously into mice subjected to 30% hepatectomy (control, 1.7% +/- 0.1%; 1 microgram hepatocyte growth factor, 6.4% +/- 1.3%; 5 micrograms hepatocyte growth factor, 18.3% +/- 0.2%) and into mice administered carbon tetrachloride (control, 12.7% +/- 1.0%; 1 microgram hepatocyte growth factor, 26.3% +/- 2.8%) or alpha-naphthylisothiocyanate (control, 0.4% +/- 0.1%; 1 microgram hepatocyte growth factor, 3.8% +/- 1.1%; 5 micrograms hepatocyte growth factor, 14.2% +/- 2.0%). In addition, weights of the remnant livers in mice given hepatocyte growth factor 60 hr after 30% hepatectomy were significantly greater than those of untreated control mice (control, 0.93 +/- 0.04 gm; 5 micrograms hepatocyte growth factor, 1.06 +/- 0.04 gm). Hepatocyte growth factor prevented any marked increase in the serum levels of liver enzymes and bilirubin when it was administered to mice also treated with alpha naphthylisothiocyanate (control: ALT, 394 +/- 278 IU/L; lactate dehydrogenase, 2,644 +/- 1,109 IU/L; bilirubin, 9.6 +/- 2.6 mg/dl; and 5 micrograms hepatocyte growth factor: ALT, 135 +/- 7.9 IU/L; lactate dehydrogenase, 1,672 +/- 626 IU/L; bilirubin, 1.0 +/- 0.8 mg/dl). Our findings show that intravenously injected hepatocyte growth factor stimulates the growth of hepatocytes in mouse liver and protects the integrity of hepatocytes in vivo against hepatitis caused by hepatotoxin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427662 TI - Inflammation and platelet-activating factor production during hepatic ischemia/reperfusion. AB - The role of platelet-activating factor as a potential mediator of hepatic inflammatory injury associated with liver ischemia/reperfusion was investigated using a partial no-flow model in rats in vivo. Platelet-activating factor levels of livers from sham-operated rats and from animals experiencing hepatic reperfusion for less than 6 hr were very low. They were observed to increase significantly after 12 hr of reperfusion and reached peak levels after a 24-hr reperfusion period, a time when maximal hepatic injury and inflammation occurred. Treatment of experimental rats with WEB2170, a platelet-activating factor receptor antagonist, attenuated the hepatic injury and inflammation, as evidenced by decreases in plasma ALT and in hepatocyte necrosis and neutrophil infiltration. Both inactivation of Kupffer cells with gadolinium chloride and inhibition of the formation of reactive oxygen species with allopurinol reduced platelet-activating factor production in the liver, whereas induction of neutropenia had no effect, suggesting that interaction of Kupffer cells with oxygen-derived free radicals may be a plausible mechanism for hepatic platelet activating factor accumulation. It is concluded that platelet-activating factor contributes to the inflammatory consequences of ischemia/reperfusion underlying late-phase hepatic injury. PMID- 1427663 TI - Differential expression of hepatocyte growth factor, transforming growth factor alpha and transforming growth factor-beta 1 messenger RNAs in two experimental models of liver cell proliferation. AB - Hepatocyte growth factor, a potent hepatocyte mitogen in vitro, appears to trigger hepatocyte regeneration after partial hepatectomy and after acute liver cell necrosis. Transforming growth factor-alpha and transforming growth factor beta 1 may also be involved in the control of liver regeneration. In this study we assessed possible roles of hepatocyte growth factor, transforming growth factor-alpha and transforming growth factor-beta 1 on liver cell proliferation in vivo, using a model of choline deficiency that is associated with liver cell necrosis and a model of a hypolipidemic agent (4-chloro-6-(2,3 xylidino)-2 pyrimidinylthio (N-beta-hydroxyethyl) acetamide) without liver necrosis. Male F344 rats were fed a choline-deficient diet or 0.16% 4-chloro-6-(2,3 xylidino)-2 pyrimidinylthio (N-beta-hydroxyethyl) acetamide diet for 6 and 4 wk, respectively. Rats were killed periodically, and the expression of hepatocyte growth factor messenger RNA in the liver, lung and kidney was determined by Northern-blot analysis. The levels of transforming growth factor-alpha and transforming growth factor-beta 1 messenger RNAs in the liver were also determined. Feeding a choline-deficient diet for 1 to 6 wk led to gradual increases in the levels of hepatocyte growth factor, transforming growth factor alpha and transforming growth factor-beta 1 messenger RNAs in the liver. Feeding a 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyethyl) acetamide diet for 3 days and 2 wk induced marked enhancement of liver cell proliferation as judged by hepatocyte 5-bromo-2-deoxyuridine incorporation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427664 TI - Identification and partial characterization of a hepatocyte-derived factor promoting proliferation of cultured fat-storing cells (parasinusoidal lipocytes). AB - The molecular and cellular mechanisms of activation of fat-storing cells (Ito cells or parasinusoidal lipocytes), a prerequisite of the fibrogenic response of injured liver, were studied by analysis in vitro of some aspects of the intercellular communication between parenchymal liver cells and fat-storing cells. Conditioned medium harvested from early serum-free monolayer cultures of hepatocytes isolated from normal rat liver stimulated strongly, reproducibly and dose-dependently the proliferation of nonconfluent fat-storing cells maintained under serum-reduced conditions. During exposure of fat-storing cells for 48 hr to the conditioned medium, the incorporation of [3H]thymidine into DNA was stimulated four to six times over control values, the DNA content per culture well was elevated by 40% above control values and the immunocytochemical detection of bromodeoxyuridine-labeled cell nuclei was increased from 13% stained nuclei in controls to 70% stained nuclei in treated fat-storing cells. The mitogenic effects of hepatocyte-conditioned medium were similar to or even higher than those of 10% fetal calf serum. No mitoinhibitory activity could be detected in the hepatocyte-conditioned medium when arginase, as a potential inhibitor, was excluded. Rat skin fibroblasts could not be stimulated under conditions where the proliferation activity of fat-storing cells was greatly enhanced. The occurrence of the mitogenic activity in the medium is not dependent on de novo synthesis or secretion because the media of hepatocytes cultured under anoxic conditions in the presence of cycloheximide, brefeldin A or ethylenediaminetetraacetate were highly active in promoting fat-storing cell proliferation, although hepatocyte viability was greatly reduced under some of these conditions. A significant positive correlation (r = 0.95, p < 0.01) was found between lactate dehydrogenase activity and the mitogenic potency of the conditioned medium. The proliferation factor for fat-storing cells could also be demonstrated in the lysate of freshly isolated hepatocytes from normal liver. The stimulatory activity in the medium was partially enriched by a combination of gel permeation and anion exchange fast protein liquid chromatography and characterized as a protein with an apparent molecular weight of about 60 kD that is heat and pH sensitive but insensitive to reducing agents. It does not bind to immobilized heparin; nor does soluble heparin or proteinase inhibitor affect the mitogenic activity of the factor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1427665 TI - Effect on the canine Eck fistula liver of intraportal TGF-beta alone or with hepatic growth factors. AB - Transforming growth factor-beta canceled the hepatocyte proliferation caused by transforming growth factor-alpha when the two substances were mixed and administered through a disconnected central portal vein branch after creation of an Eck fistula. In contrast, transforming growth factor-beta had no antidotal action on the stimulatory effects of insulin or full test doses of insulinlike factor-2, hepatocyte growth factor, epidermal growth factor or triiodothymanine. A minor antidotal effect on hepatic stimulatory substance activity could be detected, but only with hepatic stimulatory substance was given in doses smaller than those known to cause maximum stimulatory response. These results suggest a highly specific pharmacological and physiological interaction between transforming growth factor-alpha and transforming growth factor-beta in the modulation of liver growth control. PMID- 1427666 TI - Rapid donor liver nutritional enhancement in a large animal model. AB - Organ donors are typically subject to acute hyponutrition that might affect postpreservation liver function. Livers from nutritionally supplemented rats function better after preservation than livers from fasted rats. We have developed a method to glycogenate the liver of large animals in the temporal context of a human donor liver operation and have studied the fate of glycogen stores during preservation. Starved anesthetized pigs were infused with a hexose solution (glucose, fructose or galactose) by way of the superior mesenteric vein for 3 hr. Regular porcine insulin was infused to maintain a hyperglycemic hyperinsulinemic arterial glucose clamp at 12 to 16 mmol/L. Liver biopsy specimens and blood samples were taken before infusion and hourly. At 3 hr the liver was excised, stored for 24 hr at 1 degrees C in University of Wisconsin solution and biopsied. It was then placed at 20 degrees C for 1 hr to simulate the reimplantation stage of transplantation. Glycogen and nucleotide levels were measured, and results were corrected for starch in the University of Wisconsin solution. A 20% glucose infusion produced rapid hepatic glycogenation without side effects. Greater glycogenation was obtained with 20% fructose but at the cost of lactic acidosis and a fall in pH. A combination of 15% glucose and 5% fructose produced intermediary glycogenation without significant side effects. Galactose (20%) was less efficient than glucose alone. The addition of alanine and glutamine (20 mmol/L) did not significantly improve glycogenation. Metabolism of glycogen at 1 degree C did occur. Glycogen content fell 0.15% +/- 0.05% dry weight liver per hour during cold preservation and 5.49% +/- 2.15% per hour during ischemic rewarming.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427667 TI - Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis. AB - In summary, we answer the three questions we have previously posed: (a) Can liver transplantation prolong survival? Evolving data from several centers indicate that liver transplantation indeed prolongs survival in patients with PBC and PSC as compared with estimated survival using disease-specific risk scores based on the natural history of PBC and PSC. (b) Can we optimize timing of liver transplantation? Although many factors enter into the timing of liver transplantation, including when the patient is actually referred for liver transplantation and the individual desires of the patient to pursue liver transplantation, evidence is growing that having patients with chronic liver diseases like PBC and PSC undergo transplantation a little earlier in the course of the disease rather than waiting until the patients have experienced life threatening complications or are on life-support measures can indeed improve early postliver transplant survival. In patients with PBC and PSC, the survival risk score, which reflects disease severity, can serve as an objective measurement to assess and evaluate the effect of liver disease severity on transplant outcome. Indeed, a number of studies have strongly suggested that optimal timing of liver transplantation may indeed be important to improve outcome, decrease morbidity and decrease cost. (c) Does the present allocation system in the United States allow for optimal use of our scarce donor organ resource?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427668 TI - Hepatitis C among health care providers: risk factors and possible prophylaxis. PMID- 1427669 TI - Cholangitis and endoscopic drainage. PMID- 1427670 TI - Surgical management of the Budd-Chiari syndrome: no place for a procrustean bed. PMID- 1427671 TI - Chronic graft-vs.-host disease of the liver: another indication of ursodeoxycholic acid? PMID- 1427672 TI - Psychiatric lessons from the Persian Gulf War. PMID- 1427673 TI - Diagnostic issues for conversion disorder. PMID- 1427674 TI - Managed care for patients who are treatment resistant. PMID- 1427675 TI - Parallel treatment: therapy with one clinician and medication with another. PMID- 1427676 TI - An estimation of the impact of OBRA-87 on nursing home care in the United States. AB - The Omnibus Budget Reconciliation Act of 1987 (OBRA-87) established criteria for Medicare- or Medicaid-certified nursing homes to use in admitting or retaining mentally ill patients. In effect, the law created five dispositional categories for residents or potential residents of nursing homes. Using data from the 1985 National Nursing Home Survey conducted by the National Center for Health Statistics, the authors estimate what proportion of nursing home residents would fall into each of the categories. They suggest that the initial impact of the law will be to shift costs from federal programs to the states. Nursing homes will be expected to provide more mental health services. In the absence of other services, the regulations have a high potential for creating homelessness and continuing a pattern of failure to adequately serve patients with serious mental illness. PMID- 1427677 TI - Classification of amok in DSM-IV. AB - Culture-bound syndromes have been described worldwide in many individuals and, for certain syndromes, in epidemic proportion, yet these disorders have been classified as rare and exotic conditions warranting minimal attention. Development of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the tenth edition of the International Classification of Diseases offers an opportunity for providing a more sophisticated classification of these phenomena. The authors examine amok, a syndrome first described in Malaysia that consists of homicidal frenzy preceded by a state of brooding and ending with somnolence and amnesia. They discuss the concept of and criteria for a culture-specific disorder and propose that amok be classified as a culture specific explosive behavioral disorder in DSM-IV. PMID- 1427678 TI - Clinical factors associated with better quality of life in a seriously mentally ill population. AB - Improving the quality of life of persons with chronic mental illness is becoming an important treatment goal. In this study, 101 former acute care psychiatric inpatients with serious mental illness who were living in Mississippi communities were interviewed using portions of Lehman's Quality of Life Interview. A particular focus was whether clinical characteristics, such as medication compliance and social skills, that could be changed by interventions were associated with patients' ratings of their quality of life. Self-reports of better quality of life were associated with fewer depressive symptoms, fewer medication side effects, and better family interactions. Results indicate that clinical interventions to improve quality of life in this population should include family psychoeducational programs and better detection, evaluation, and treatment of both depressive symptoms and side effects of medication. PMID- 1427679 TI - Case management, quality of life, and satisfaction with services of long-term psychiatric patients. AB - Two scales developed in Great Britain, the QOL Profile and the General Satisfaction Questionnaire, were used to examine the relationship between type of case management services and quality of life and satisfaction with treatment of 68 long-term psychiatric patients in Colorado. Factor analysis identified three types of case management activities that tended to occur together: assertive outreach (direct help, out-of-office visits, and monitoring), brokerage (referral to other agencies), and counseling and assessment. Monitoring was the only variable positively associated with quality of life for all patients; brokerage was the only variable negatively associated with acceptability of services. The number of case management contacts was negatively associated with treatment satisfaction. PMID- 1427680 TI - Patient outcome after transfer within a psychiatric hospital. AB - Patients' satisfaction with the process and outcome of transfer between units of a private psychiatric hospital and the immediate impact of the transfer were examined through chart reviews (59 patients) and interviews (29 of the 59 patients). Results suggested that most patients were satisfied with the transfer and were not adversely affected by it. Satisfaction was positively correlated with briefer hospitalization, feeling better (less anxious or depressed) after transfer, and being informed ahead of time about the program on the new unit. The adversely affected patients had fewer previous hospitalizations at the current facility, were transferred sooner after admission, and had briefer current stays. No relationship was found between adverse effects and dissatisfaction. Patients suggested that better communication, more information about the new unit, and more advance notice would be helpful. PMID- 1427681 TI - Treatment-resistant chronic mental illness: is it Asperger's syndrome? AB - In some cases of treatment-resistant chronic mental illness, it may be useful to reconsider the primary diagnosis. Patients with Asperger's syndrome, a rare pervasive developmental disorder, have characteristics such as eccentricities, emotional lability, anxiety, poor social functioning, repetitive behavior, and fixed habits that can mimic symptoms of other illnesses, including schizophrenia spectrum illness, bipolar disorder, anxiety disorders, and obsessive-compulsive disorder. Their disorganizing anxiety in response to stress, which may be accompanied by increased oddness of speech, can easily be misinterpreted as psychosis. The author describes features of Asperger's syndrome, discusses differential diagnosis, and presents care examples. A habilitative treatment plan that concentrates on modifying the patient's eccentricities into strengths and carefully tailors the work and living situation may be effective with some patients. PMID- 1427682 TI - Classification and characteristics of Army stress casualties during Operation Desert Storm. AB - During the Persian Gulf War, the U.S. Army provided mental health care to soldiers using a model that emphasized the identification and management of factors associated with combat stress. Nonpathological labels, such as combat stress reaction, a non-hospital-based care delivery system, and simple interventions were used to promote return to duty. The authors describe such services provided to the U.S. Army 7th Corps. A total of 158 patients were treated; 72 percent were men. Seventy percent were from the junior ranks. Thirteen soldiers were treated for axis I disorders, four for axis II disorders, and 118 for stress reactions. Ninety-nine percent of the soldiers treated were returned to effective duty after a brief intervention. PMID- 1427684 TI - Cultural influences in psychotherapy with refugee survivors of torture and trauma. AB - A selective review of the literature describing treatment of refugee survivors of torture and trauma revealed that approaches to psychotherapy used in treating South American patients differed from those used in treating Indochinese patients. South American patients were receptive to psychodynamic psychotherapeutic approaches that focused on detailed recollection of past trauma. Indochinese patients responded to a broader-based rehabilitation approach that could include psychotropic medication, supportive psychotherapy, and assistance in meeting practical needs. The authors suggest that many of the differences in treatment of the two groups may be attributed to cultural factors, with South American patients reflecting an affinity for the Western philosophical assumptions in which psychodynamic therapy is rooted and Indochinese patients reflecting a cultural background that values responsibility to the group, deference to authority, and restrained modes of emotional expression. PMID- 1427683 TI - Clinical presentation of PTSD in World War II combat veterans. AB - Clinicians have increasingly recognized posttraumatic stress disorder (PTSD) among Vietnam veterans, but the disorder may be easily overlooked among World War II combat veterans. The authors review recent studies of PTSD in older veterans and describe five cases that illustrate the diverse clinical presentations of PTSD in this population. Symptoms included anxiety, cognitive and somatic complaints, depression, alcohol dependence, and amnestic periods. Despite the varied presentations, a fairly consistent patient profile emerged. Patients avoided reminders of war, showed an exaggerated startle response, and experienced restless sleep and chronic anxiety. Factors associated with exacerbations of symptoms were retirement and reminders of war experiences. Although past studies have emphasized resuppression of the trauma, the authors encourage a flexible approach to treatment, including exploratory techniques. PMID- 1427685 TI - Social issues in the management of released hostages. AB - Mental health clinicians have assumed a more important role in the release of individuals held hostage by international terrorists. The author uses his experiences during three hostage releases in the late 1980s--the Achille Lauro incident, the hijacking of Pan Am Flight 73 in Karachi, Pakistan, and the release of a single hostage from Beirut--to illustrate important factors in managing victims. He describes an intervention model that emphasizes the importance of creating a healing social environment immediately after release. Such an environment encourages strong cohesiveness within the victim group, isolates the victims from external groups, promotes abreaction, and provides an opportunity for rest and replenishment. Interventions are made to restore a sense of power to the victims and to reduce their feelings of isolation and helplessness and of being dominated by the terrorists. PMID- 1427686 TI - Effectiveness of a stress recovery unit during the Persian Gulf War. PMID- 1427687 TI - Posttraumatic stress symptoms among soldiers exposed to combat in the Persian Gulf. PMID- 1427688 TI - State hospital patients' views about Operation Desert Storm. PMID- 1427689 TI - Incidence of PTSD among staff victims of patient violence. PMID- 1427690 TI - A collaborative nurse-physician practice model for helping persons with serious mental illness. PMID- 1427691 TI - Disability status and length of stay at a VA medical center. PMID- 1427692 TI - A new system of care for the homeless mentally ill. PMID- 1427693 TI - "The chronic patient": in search of a title. PMID- 1427694 TI - A model for community practice. PMID- 1427695 TI - Interpersonal psychotherapy of depressed HIV-positive outpatients. AB - In an open pilot study, 23 depressed adults infected with human immunodeficiency virus were treated using interpersonal therapy. Twenty subjects recovered from depression after a mean of 16 sessions. The authors discuss six aspects of interpersonal therapy that make it useful with depressed HIV-infected persons: psychoeducation about the sick role; a here-and-now framework; formulation of problems from an interpersonal perspective; exploration of options for changing dysfunctional behavior patterns; identification of focused interpersonal problem areas (grief, role transition, interpersonal disputes, and interpersonal deficits); and the confidence therapists gain from a systematic approach to problem formulation and treatment. Results suggest that mental health professionals should consider interpersonal therapy as a treatment for depressed HIV-positive patients. PMID- 1427696 TI - A group approach to psychosocial issues faced by HIV-positive women. AB - Women now constitute the fastest-growing population of persons with AIDS in the U.S. The psychosocial problems of women with AIDS and HIV infection are underrecognized, and economic, personal, and social resources to meet their needs are often inadequate. The authors describe development of a group for HIV infected women and discuss issues raised by group members. HIV-infected women often feel isolated and experience stigma and shame. Their roles as caregivers and as wives and mothers are often changed or lost, and they experience anxiety and confusion about options for sexual activity. They sometimes fear transmitting HIV to family members through non-sexual contact. Physicians may discount their symptoms and may need to be educated about gynecological problems associated with HIV. Other issues involve coping with being both ill and a mother, disclosing information to children about the illness, and loss of reproductive choice. PMID- 1427697 TI - Involvement in productive activities and satisfaction with living situation among severely mentally disabled adults. AB - Eighty-three adults with severe mental disabilities participated in a study examining effects on life satisfaction of having nothing to do, receipt of a housing subsidy, and enrollment in an intensive case management program. The clients were divided into four groups receiving subsidized housing and intensive case management, subsidized housing and nonintensive case management, intensive case management and nonsubsidized housing, and nonintensive case management and nonsubsidized housing. Initially and at ten months, clients reported how much time they spent with nothing to do and their level of satisfaction with supported living arrangements. A significant association was found between time spent with nothing to do and both satisfaction and change in satisfaction and between having a housing subsidy and satisfaction. Results suggest that getting clients involved in activities of their own choosing would result in much greater increases in satisfaction. PMID- 1427698 TI - A report on the "worst" state hospital recidivists in the U.S. AB - A total of 196 nonspecialty state hospitals in the U.S. each identified one patient--referred to as the hospital's "worst" recidivist--admitted to the hospital in 1987 who had the most lifetime admissions to that hospital. Persons admitted for mental retardation or substance abuse detoxification were excluded. The mean age of the recidivists was 42.2 years; their mean age at first admission was 24.7. The number of admissions per patient ranged from five to 121, with a mean of 31. Compared with the national population of state hospital admissions, significantly larger proportions of recidivists had diagnoses of schizophrenia, bipolar disorder, and personality disorder. More research is needed to determine actual community tenure of patients who receive revolving-door care and whether alternative approaches would be more effective. PMID- 1427699 TI - A clozapine treatment program for patients living in the community. AB - Clozapine treatment for schizophrenic patients living in the community requires strategies to ensure safe use of the medication and to foster patients' emerging social and living skills. The authors describe a clozapine treatment program in a community mental health center that includes a weekly clozapine support group meeting followed by drawing of blood for monitoring of side effects. Case managers and other program staff remind patients to take clozapine as prescribed and help them comply with hematological monitoring requirements, manage side effects, deal with the emotional aspects of improvement, and benefit from emerging capabilities. About 75 percent of the center's patients who have been offered clozapine have decided to take the medication, and almost all patients in the clozapine treatment program have experienced significant symptom relief and functional development with manageable side effects. PMID- 1427700 TI - Length of time spent in seclusion and restraint by patients at 82 VA medical centers. AB - Analysis of data from 82 Veterans Affairs medical centers showed that during a one-year period in 1987-88, VA psychiatric inpatients spent about 240,000 hours in seclusion or restraint, with about half of that time in mechanical restraints. The median length of time patients in each medical center spent in seclusion and restraint was used to classify centers as having "higher" or "usual" rates of use of those techniques. In the 20 centers classified as higher users, patients spent two to three times longer in seclusion and restraint per incident than patients in the 62 centers classified as usual users. Time spent by patients in seclusion and restraint in centers with usual rates of use was consistent with reports from other U.S. studies. The longer time in seclusion and restraint per incident in higher-user centers may be due to characteristics of the medical center or of the patient population. PMID- 1427701 TI - Do-not-resuscitate orders for depressed psychiatric inpatients. AB - Many patients, especially those who are elderly and who have chronic medical illnesses, choose to forgo cardiopulmonary resuscitation (CPR) in case of cardiac arrest. The right of mentally competent patients to refuse CPR is supported by ethicists, the courts, and medical associations. Psychiatrists are increasingly presented with dilemmas about resuscitation preferences of elderly psychiatric inpatients whose decision-making capacity may be impaired because of mental illness such as depression. The authors discuss justifications for patients' refusing resuscitation, the role of advance directives in communicating patients' preferences, and the use of do-not-resuscitate orders for depressed psychiatric inpatients. Survival rates after CPR among elderly patients with chronic medical illnesses are low. Patients and their families need accurate information about the risks and benefits of CPR and about the consequences of refusing the procedure. PMID- 1427702 TI - Improving psychiatric environments through minimal architectural change. AB - Minimal architectural changes in a treatment environment can lead to significant improvements in how the setting functions, with positive effects for staff, patients, and families. When a mental health center located in an antiquated hospital in Jerusalem added five additional entrances, the change improved accessibility, increased the sense of freedom, and helped define the identity of the units. Other therapeutic effects were obtained from minimal modifications in a day hospital unit, including brightening paint and changing lighting, reopening a separate stairway for use by patients not enrolled in the day unit, and defining separate living, dining, and personal-expression areas within the common room. The authors note that cooperation between the disciplines of architecture and psychiatry is essential and that the idea of change as a continuous process should be incorporated into an organization's culture. PMID- 1427703 TI - Countertransference and clinical choices in public-sector treatment of a patient and her family. AB - Clinical decision making in the treatment of families of individuals with prolonged mental illness can be affected by countertransference that is stimulated by the context of treatment as well as by the family being treated. For clinicians, psychoeducation, the current intervention of choice for such families, can serve defensive functions that are motivated by counter transference; a case example illustrates how such defenses led a clinician to avoid deeper therapeutic work. The authors believe that clinicians must strive to understand their motivations for whatever clinical decisions they make; to facilitate this awareness, intensive psychotherapy should be required as an adjunct to training. PMID- 1427704 TI - The therapist as psychoeducator. PMID- 1427705 TI - Response to day hospital treatment by patients with cocaine and alcohol dependence. PMID- 1427707 TI - A standardized mental status examination discriminating four major mental disorders. PMID- 1427706 TI - Medical necessity scales for inpatient psychiatric concurrent review. PMID- 1427708 TI - Dementia praecox: inescapable fate or psychiatric oversight? PMID- 1427709 TI - Prenatal care for pregnant chronic mentally ill patients. PMID- 1427710 TI - Consultation-liaison models. PMID- 1427711 TI - Montana agrees to pay $350,000 damages for rights violations of state hospital patients. PMID- 1427712 TI - Data watch. AHA: adjusted admissions hit new high in 1991. PMID- 1427713 TI - Hospitals cope with America's new 'family value'. AB - It's not a new problem, but the attention it's getting is growing every day. Domestic violence, or family violence, a concept that encompasses child abuse, partner abuse, and elder abuse, is being understood more and more as a trauma to the nation's families. Very often it's hospitals, particularly hospital emergency departments, that are the first community organization that the abused person sees for examination or treatment. The question is, are hospitals prepared? In a comprehensive look at the problem and some possible approaches to solving it, Hospitals senior correspondent Frank Sabatino talks to the experts in every area touching on this complex, tragic societal issue. PMID- 1427714 TI - Vendors worry: will health reform place technology on trial? AB - The outcome of the reform debate will have an enormous impact on the health care vendor community as well as on providers. With arguments swirling about regarding such issues as technology costs, vendors offer their views of reform. PMID- 1427715 TI - Tax-exempt challenges continue. AB - National attention to the tax-exempt status issue is not as acute as it has been in the last few years, but the challenges are continuing in a number of states. Hospital administrators and legal experts in Pennsylvania, the nation's flashpoint state on the issue, discuss what's going on and why. PMID- 1427716 TI - Employment of full-time staff outpaces part-time growth. AB - Data from the AHA's Hospital Panel Survey show faster growth in hospitals' full time staffs than in their part-time staffs in the first six months of the year. And slower labor cost growth was offset by fast non-labor cost growth. PMID- 1427717 TI - Surveying customer needs, not satisfaction, is crucial to CQI. AB - Experts say that understanding the differences between customer needs and customer satisfaction is crucial to hospitals' success in quality management. And hospitals on the leading edge are applying that theory to their programs. PMID- 1427718 TI - Medical imaging. Hospitals give renewed attention to service, costs, flow of images. PMID- 1427719 TI - Jim Brady speaks out on handgun violence. PMID- 1427721 TI - CEOs: planning next career move no easy task. PMID- 1427720 TI - Contract-management careers: risks, rewards. PMID- 1427722 TI - Hospitals see worker shortages continue. PMID- 1427723 TI - Experts urge closer look at hospital investment policies. PMID- 1427724 TI - MD training key factor in prevention. PMID- 1427725 TI - Moving from competition to collaboration. PMID- 1427726 TI - Observers see Clinton moving quickly on health care reform. AB - The 1992 presidential election was about a lot of things, from the economy to taxes to education. Health care reform played a major role in the public policy debate, and the different approaches taken by the candidates on that issue helped define them. A look at the result and what it may mean for the health care field. PMID- 1427727 TI - Data watch. Projected growth in top outpatient procedures. PMID- 1427728 TI - 12 cost-cutting measures. Hospitals use creative ideas to gain control of expenses. AB - With operating costs ever rising and reimbursements ever tightening, hospitals are looking for ways to cut costs at every turn. The good news is that there are a lot of innovative, imaginative approaches being tried in every area of hospital operations--approaches that don't require massive financial investment, organizational restructuring, or teams of outside consultants. The examples we've found through talking with hospitals across the country are a fair sample of the types of opportunities out there. They range across the entire hospital, from the laboratory to the pharmacy to nursing to waste management to the medical staff to the operating suite. In other words, something for everyone. PMID- 1427729 TI - 1991 data: low interest rates cut both ways for hospitals. AB - Low interest rates proved to be a mixed blessing for hospitals in 1991, as many capitalized on plummeting interest rates by refinancing existing debt. And though lower rates caused investment income to shrink, one CEO notes that, because most hospitals have higher debt loads than investment income, the situation has proven to be a net positive for that majority. PMID- 1427730 TI - Ambulatory care strategic plans outline hospitals' new priorities. AB - With more and more of hospitals' clinical services shifting to the outpatient sector, the issue of whether to have a separate strategic plan for ambulatory care is growing more prominent. Hospitals that have such plans cite many advantages. PMID- 1427731 TI - Economic forces drive collaboration push. AB - Over 60 percent of CEOs surveyed say their hospital will belong to a regional, integrated health system by 1995. The question, they say, is not whether integration will happen, but how. PMID- 1427732 TI - Hospitals tap incinerator steam to run laundry. PMID- 1427733 TI - Expert shows path to collaborative success. PMID- 1427734 TI - TV show helps Henry Ford reach Detroit's children. PMID- 1427735 TI - Medical record analysis can show legal risks. PMID- 1427736 TI - Big response to free Data Bank software. PMID- 1427737 TI - TQM: health care can learn from other fields. PMID- 1427738 TI - Health transition: examples from the western Pacific. PMID- 1427739 TI - Studies of cardiovascular disease and cause-specific mortality trends in Japanese American men living in Hawaii and risk factor comparisons with other Japanese populations in the Pacific region: a review. AB - The Honolulu Heart Program (HHP) is a long-term prospective epidemiologic study of cardiovascular disease (CVD) in male descendants of Japanese migrants to Hawaii. The article is a review of data from recent and past HHP studies relevant to the Seventeenth Pacific Science Congress symposium "Changes in Disease Patterns in the Western Pacific and Southeast Asia." The Ni-Hon-San Study, which compared CVD rates and risk factors in Japanese men living in Japan, Hawaii (HHP), and California, showed that coronary heart disease (CHD) and stroke mortality rates in Hawaii were intermediate between rates in Japan and California. Gradients in CVD risk factors were similar to the gradients in disease rates. From 1966 to 1984 trends in incidence rates for CHD, stroke, and cause-specific mortality were compared for the 8006 participants and 3130 non participants in the HHP. CHD and stroke rates declined by about 40% for the total HHP cohort. There was a larger decline for CHD mortality (over 60%) in the nonparticipants. There was also a much greater decline in total mortality and cancer mortality rates in the nonparticipants. The results of the reviewed studies show that the subjects, although sharing a common ethnic background, experience different rates of disease when living in diverse geographic and cultural locales. This finding supports evidence that environmental and behavioral factors influence chronic disease rates and provides a basis for intervention and prevention. The finding that nonparticipants in epidemiologic studies can show different incidence trends suggests that caution should be used in interpreting trends limited only to participants. PMID- 1427740 TI - Temporal changes and rural-urban differences in cardiovascular disease risk factors and mortality in China. AB - We summarize several studies, from the last 10 years, of temporal changes and rural-urban differences in the risk factors of cardiovascular disease (CVD) in China to indicate the influences of economic modernization. Two national blood pressure surveys have shown that the prevalence of hypertension increased from 5.1% to 7.7% between 1958-1959 and 1979-1980. Throughout China hypertension is more prevalent in urban areas than in rural areas. Within the Shanghai region body mass index, blood pressure, and total serum cholesterol were higher in urban districts than in rural areas. Rural-urban differences in lipid levels were also found in the Beijing and Guangzhou regions. A related four-year followup study showed that total serum cholesterol and triglycerides increased markedly in both urban and rural areas of Guangzhou. In Shanghai part-time farmers who worked in factories had a higher age-adjusted prevalence of definite hypertension than farmers who worked full-time in the fields (5.0% versus 2.3%). In a prospective study in Wuhan a new productivity-based salary system was associated with increased serum cholesterol and blood pressure. Age-adjusted CVD mortality increased from 1973 to 1982 in a rapidly industrializing county in the Shanghai metropolitan region. The results from several studies indicate that China is undergoing the expected increase in modernization-related CVD risk factors and mortality, especially in urban metropolitan regions. PMID- 1427741 TI - Causes and consequences of increase in child survival rates: ethnoepidemiology among the Hmong of Thailand. AB - The Hmong "hill tribe" minority in Thailand has much higher exposure to factors usually associated with risk of child mortality (high fertility, low status of women, low education, less use of modern medical care for births, exposure to warfare, economic and physical disruption, and poor hygienic conditions) than the rural ethnic Thai population. Nonetheless, infant mortality has declined from over 120 per 1000 to under 50 per 1000 live births among both these populations in the past 30 years. The reason for the rapid increase in child survival among the Hmong appears to be better access to and more use of modern curative and preventive medical care associated with road construction rather than major changes in social or hygienic conditions. Conventional wisdom suggests that high fertility is both a cause and a consequence of high infant and child mortality and that parents will not reduce fertility until they see that mortality has declined. Most Hmong parents recognize the decline in child mortality and attribute it to better access to modern medical care. Most Hmong parents also say that, if they were starting to have children now, they would want to have fewer children. Fear of child death is infrequently mentioned as a motive for having more children, and the perceived decline in child mortality is rarely mentioned as a reason for reduced fertility. Most Hmong parents explain their desired family size in terms of economic conditions rather than perceived risk of child mortality. Results of this study suggest that fertility and child mortality can vary independently of one another and that major reductions in child mortality can be accomplished without waiting for major social changes (e.g., improved education or status of women) or major reductions in fertility. PMID- 1427742 TI - Human T-cell lymphotropic virus type I infection and disease in the Pacific basin. AB - Human T-cell lymphotropic virus type I (HTLV-I), the cause of adult T-cell leukemia/lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), is widespread in the Pacific basin. Modes of virus transmission include blood transfusion (and intravenous drug use), breast milk, and sexual intercourse. High prevalences of HTLV-I infection and disease occur among the inhabitants of southwestern Japan and among first- and second generation (issei and nisei) Japanese-Americans in the Hawaiian Islands. Other Pacific populations with high prevalences of HTLV-I infection include several remote groups in West New Guinea, Papua New Guinea, the Solomon Islands, and Vanuatu, which have had no contact with Japanese or Africans. By contrast, Micronesian and Polynesian populations, even those with prolonged contact with Japanese, exhibit low prevalences or no evidence of HTLV-I infection. Low prevalences of infection are also found in Australia, except among some aboriginal populations. Changing patterns of HTLV-I infection and disease are no better exemplified than in Japan, where striking reductions in transfusion acquired infection and subsequent development of HAM/TSP have followed the institution of nationwide screening of blood donors for HTLV-I infection. Furthermore, virus transmission from mother to infant by means of infected breast milk has been markedly curtailed in HTLV-I-hyperendemic regions in Japan by interrupting the practice of breast feeding by HTLV-I-infected mothers. The next frontier of HTLV-I research is in Melanesia, where highly divergent sequence variants of HTLV-I have been discovered. PMID- 1427743 TI - Genetic disease patterns in Japan: a review. AB - Comprehensive genetic studies in which the genetic structure of a population is considered against the background of ecological factors, including environmental and social variables, often supply valuable information for the solution of a number of problems in human biology, including reproductive compensation and inbreeding depression. In the first section of this paper we consider the incidence of genetic diseases in Japan in reference to other populations. Some of the genetic disorders found elsewhere do not occur or are of lower frequencies in Japan. On the other hand, a number of genetic diseases occur at higher than usual frequencies, leading to an incidence of genetic disease of the order of about 1 per 100 in newborn Japanese. We next review the studies of consanguinity in Japan and report evidence of very high levels, ranging from 8.6% to 58.0%, for villages during the early part of the twentieth century. The rates are declining rapidly for the country but, because of traditional social values, inbreeding rates remain significant in many small villages. In the final section we consider the probable trends in the frequency of inbreeding on a worldwide basis and point out that frequencies of certain genetic diseases are likely to remain high and even increase in some societies because of various socially prescribed mating patterns. PMID- 1427744 TI - Familial resemblance of blood pressure with residual household environmental effects in consanguineous and nonconsanguineous families from Andhra Pradesh, India. AB - Familial aggregation of blood pressure (BP), both systolic (SBP) and diastolic (DBP), was examined in consanguineous and nonconsanguineous families from southern India. Path analysis of BP suggests inbreeding effects, with the genetic variance for SBP being lower in the sample that included inbred families. Specifically, genetic heritability for SBP was 38% in the nonconsanguineous sample but only 23% in the combined sample. Genetic heritability for DBP (30%) did not vary by sample, nor were sample differences in cultural heritability detected for either SBP (over 35%) or DBP (about 18%). These findings are remarkably similar to those in a French-Canadian population of Quebec; both reports found a considerably larger effect of the home environment on BP than previous studies. PMID- 1427745 TI - Importation route of the sickle cell trait into Portugal: contribution of molecular epidemiology. AB - To elucidate the origin and spread of the sickle cell trait into the Portuguese population, we examined nine polymorphic DNA markers within the beta globin gene cluster defining the haplotype. The population sample included 64 sickle-cell gene-bearing individuals from defined Portuguese-speaking white, black, and Asian Indian populations. The nature and geographic distribution of the different beta S haplotypes in Portugal suggest that the sickle cell trait has been imported twice: between the eighth and the thirteenth centuries from the Mediterranean basin (in association with the Benin haplotype) and after the fifteenth century from black Africa over an Atlantic route (Senegal and Bantu haplotypes). PMID- 1427746 TI - Genetic heterogeneity and population structure of Gond-related tribes in the Vidarbha region of Maharashtra. AB - Genetic heterogeneity in nine polymorphic loci is observed among Gond-related tribes in the Vidarbha region of Maharashtra. Pardhans, with their high ABO*A2 gene frequency (4.01%), low m gene frequency (57%), high P*1 gene frequency (42.7%), and high HbS trait (31.58%), differ significantly from other tribes. Per locus average heterozygosity among the studied tribes ranged from 36.24% to 40.37%, with Pardhans being more heterozygous. Analysis by FST and the empirical relationship between average allele frequencies and the ratio of within-gene to total gene diversity show that the tribes are isolated and that differentiation among them is at an early stage and approximately in conformity with expected differentiation under genetic drift. However, distances and principal components analysis reveal that Pardhans are far removed from the other tribes and from other central Dravidian tribes. Furthermore, of the various demographic parameters estimated, the high average heterozygosity in Pardhans is significantly correlated with mean marital distance (MMD), regression of MMD on wife's age, and effective population size. There is congruence between genetic and demographic data, showing that Pardhans are distinct. This conforms with Haimendorf's (1979) contention based on cultural traits that Pardhans are Gonds by historical accident and are later migrants to the Gond area from the north. The most significant and practical observation of the present study is that migration from an originally nontribal (Pardhan) to a tribal (Gond) area and admixture lead to severe disease course, differential selection pressure, and hence highly elevated HbS trait frequency. PMID- 1427747 TI - The emerging role of molecular diagnostics in surgical pathology. PMID- 1427749 TI - Expression of the bcl-2 oncogene product and chromosomal translocation t(14;18) in Hodgkin's disease. AB - The B-cell lymphoma/leukemia oncogene bcl-2 takes part in crucial regulatory events in B-cell maturation and differentiation. The reciprocal chromosomal translocation t(14;18), leading to overexpression of this oncogene, can be found in the majority of follicular lymphomas and much less frequently in B-cell leukemias and diffuse lymphomas. We have studied the expression of this protein in different subtypes of Hodgkin's disease using monoclonal antibodies directed against a formalin-resistant epitope of the bcl-2 protein and also have investigated these cases by polymerase chain reaction for evidence of the t(14;18) translocation. We were particularly interested to determine whether nodular paragranuloma (lymphocyte-predominant, nodular), which differs from other subtypes of Hodgkin's disease by virtue of the B-cell nature of its malignant cell population, is characterized by expression of the bcl-2 protein. Our data indicate that only a small number of nodular paragranulomas express the bcl-2 protein and that the expression is not specific for this type of Hodgkin's disease. In a smaller number of cases this expression of bcl-2 could be explained by the presence of the translocation t(14;18). PMID- 1427748 TI - Concurrent mutations of coding and regulatory sequences of the Ha-ras gene in urinary bladder carcinomas. AB - This report concerns the study of Ha-ras gene mutations and ras p21 expression in primary tumors of the urinary bladder. Polymerase chain reaction-based techniques and computerized image analysis were used. The data obtained were related to tumor grade, DNA ploidy, and tumor invasion. A point mutation (G-->T) at Ha-ras codon 12 was found in 30 of 67 tumors. The mutation frequency was greater in grade III (65%) than in grade II (44%) tumors; no mutations were observed in grade I tumors. The mutation was observed more often in aneuploid (58%) than in diploid (28%) tumors. No other substitution at codon 12 was seen and no codon 61 mutation was detected. The tumors were also tested for the A-->G mutation at position 2719 of Ha-ras intron D. Concurrent codon 12 and intron D mutations were identified in seven high-grade aneuploid tumors; six were invasive. The levels of the ras gene product p21 were approximately 10 times higher in tumors with intron D mutation than in those without. These findings confirm on human bladder tumors the observations of the effect of synchronous exon-intron mutations reported on the bladder cancer cell line T24. Our results are the first demonstration of Ha ras intron D alterations in human tumor tissues and suggest that concurrent mutations at codon 12 and intron D of this gene within the same tumor may contribute to the aggressive behavior of human bladder carcinomas. PMID- 1427750 TI - Computerized morphonuclear characteristics and DNA content of adenocarcinoma of the pancreas, chronic pancreatitis, and normal tissues: relationship with histopathologic grading. AB - We report the morphonuclear characteristics of normal (13 cases), benign (ie, chronic) pancreatitis (six cases), and neoplastic (ie, ductal) adenocarcinoma (22 cases) tissues of the pancreas. This description is based on computerized cell image analysis, which permits the determination of parameters related to the morphometric (nuclear area), densitometric (nuclear DNA content), and chromatin texture features of Feulgen-stained nuclei from paraffin-embedded archival material. We observed that nuclear area discriminates between normal and benign (ie, chronic pancreatitis) as opposed to neoplastic cell nuclei. Morphonuclear parameters describing chromatin pattern characteristics made it possible to discriminate between grade I pancreatic carcinoma and normal and benign cell nuclei on the one hand, and grades I and III carcinoma on the other hand. The nuclear DNA content increased in a continuous manner from normal and benign through low-grade to high-grade neoplastic tissues of the pancreas. Combining the morphometric, densitometric, and textural parameters into one equation, we were able to calculate a score (ie, the malignancy level index) that showed a close relationship to conventional histopathologic grading. Thus, the computer-aided diagnosis of cytologic specimens from pancreatic lesions offers information of the same significance as that obtained by conventional histopathologic grading. PMID- 1427751 TI - Pulmonary vascular involvement in sarcoidosis: a report of 40 autopsy cases. AB - We examined pulmonary vascular involvement in 40 autopsy cases of sarcoidosis. In these cases granulomatous involvement was observed at all levels from large elastic pulmonary arteries to venules, and venous involvement was more prominent than arterial involvement. The extent of granulomatous vascular involvement was related to that of parenchymal granuloma. No significant difference was found between upper and lower lobes in the incidence of granulomatous vascular involvement. The distribution of granulomata in the blood vessels was segmental and adventitial, and medial involvement was prominent in the larger vessels. Healed lesions of granulomatous vascular involvement also were observed at various levels in blood vessels. Prominent granulomatous involvement was found in the lymphatic capillaries and collecting lymphatic vessels in lungs with sarcoidosis. Serial sections of the lungs demonstrated interstitial granuloma directly connecting the lymphatic capillaries around small blood vessels. Granulomatous involvement in vasa vasorum and lymphatic capillaries is likely to be an important factor in the pathogenesis of granulomatous vascular involvement in lungs with sarcoidosis. The present study suggests that granulomatous vascular involvement and its sequelae may contribute to the development of pulmonary sarcoidosis. PMID- 1427752 TI - Morphologic findings and causes of failure in 24 explanted Ionescu-Shiley low profile pericardial heart valves. AB - From 1981 to 1987 just over 608 Ionescu-Shiley low-profile bovine pericardial bioprostheses were implanted at the Toronto Hospital. Twenty-four prostheses (11 aortic and 13 mitral) were surgically explanted from 1988 to 1990 from 20 adults (10 men and 10 women). Prosthesis failure was caused by primary tissue failure in 17 valves or by other mechanisms in seven valves. Variable degrees of tissue failure were also seen in four of the seven valves from the latter group. Primary tissue failure was characterized by fluid insudation between collagen bundles, para stent post tears (alignment stitch related, 20 valves), cusp perforation with prolapse, and calcification. The earliest cusp tears occurred at 28 months. Calcification (10 of 24 cases) was minimal in seven of 10 valves (occurring primarily at the margins of the torn cusp), moderate in two, and severe in one. Tissue overgrowth (pannus) was seen in all but three prostheses. Like its predecessor, the Ionescu-Shiley standard pericardial valve, this prosthesis failed at 2 to 5 years largely due to design-related (alignment stitch) causes and tissue degeneration. Calcification was less prominent, while tissue overgrowth (pannus) was more marked. PMID- 1427753 TI - False aneuploidy in benign tumors with a high lymphocyte content: a study of Warthin's tumor and benign thymoma. AB - The quality of results of flow cytometric DNA content analysis of formalin-fixed, paraffin-embedded tissue may be affected by a number of preanalytical variables. We performed flow cytometric DNA content analysis on two types of benign tumors to investigate the effect of a prominent lymphocytic component: Warthin's tumor (N = 20) and benign thymoma (N = 8). Malignant tumors (N = 23) were included as DNA aneuploid controls. All tissues studied were archival material processed using Hedley's technique either without prolonged rehydration in water (day 0 samples) or with 24- or 48-hour rehydration (day 1 and day 2 samples, respectively). Image cytometric DNA ploidy analysis was also performed on most cases. Eight cases (40%) of Warthin's tumor and five cases (63%) of benign thymoma showed either hyperdiploid peaks or marked asymmetry on the day 0 DNA histograms; nine of the malignant tumors were aneuploid. The DNA histogram abnormalities of the benign tumors could be gated out by excluding the lymphocyte nuclei. None of the DNA indices of the benign tumors corresponded with expected deviations based on published chromosomal studies. All of the DNA histogram abnormalities of the benign tumors disappeared and/or fused with the main peaks on the day 1 or day 2 samples, except for one case of benign thymoma. All the DNA aneuploid peaks on the malignant tumors persisted with prolonged rehydration. Image cytometric DNA analysis showed a diploid pattern in all benign tumors. We conclude that a high lymphocyte content may be a cause of false aneuploidy in these benign tumors. Furthermore, the degree of rehydration appears to be an important factor in achieving optimum fluorochrome staining of DNA. PMID- 1427754 TI - Necrotizing funisitis: a study of 45 cases. AB - Necrotizing funisitis (NF) is a distinctive inflammatory condition of the umbilical cord, characterized by perivascular concentric rings of inflammatory cells, necrotic debris, or calcium deposits. Necrotizing funisitis has been strongly associated with syphilis by some investigators, while others have failed to link NF with any consistent infectious agents. We examined 45 cases of NF to determine its relationship with syphilis. Five (11%) mothers had syphilis as confirmed by a positive rapid plasma reagin test and a positive fluorescent antibody absorbed test, 31 (69%) had a negative rapid plasma reagin test or venereal disease research laboratory test, and test results were not available for the remaining nine (20%). There was no record of syphilis in those babies born to mothers without confirmed syphilis. Estimated gestational age at the time of delivery ranged from 18 to 40 weeks (mean, 28 weeks). Prolonged rupture of membranes was present in 28 (62%) of the mothers, and ranged from 1 to 51 days (mean, 9 days); this was the most frequently seen maternal factor in connection with NF. Fourteen (31%) of the babies were stillborn or nonviable, including three (60%) of the five born to mothers with syphilis. Maternal and fetal cultures revealed no consistent microorganisms. Placental histology was significant for chronic villitis in 26 (58%) cases, including all five (100%) with maternal syphilis. Acute chorioamnionitis was present in each case (100%) and varied from mild to severe. We conclude that (1) NF has a polymicrobial etiology, (2) in the absence of other placental findings associated with syphilis NF should not be considered presumptive of this disease, and (3) factors leading to NF may also contribute to acute chorioamnionitis, premature rupture of membranes, and stillbirth. PMID- 1427755 TI - Distribution of transforming growth factor-beta 1 in human astrocytomas. AB - We used immunohistochemical techniques to study the distribution of transforming growth factor-beta 1 (TGF-beta 1) and infiltrating lymphocytes and macrophages in human astrocytomas. Thirteen of 15 grade 4 astrocytomas (glioblastomas) showed staining with anti-TGF-beta 1 antibody, predominantly in proliferating endothelial complexes and surrounding small and medium-sized blood vessels. Brain tissue microscopically free of tumor cells (n = 8) and more differentiated astrocytomas of varying grade (1 to 3; n = 6) devoid of endothelial proliferation did not stain with anti-TGF-beta 1. Normal brain contained only rare lymphoreticular cells. The majority of astrocytomas studied, however, contained T lymphocytes and macrophages with smaller numbers of B lymphocytes. The lymphoreticular infiltrates were concentrated primarily in close proximity to blood vessels. Within an individual tumor perivascular regions staining for TGF beta 1 never contained more than occasional T lymphocytes. Perivascular regions not staining for TGF-beta 1 frequently contained low to high numbers of T lymphocytes. The inverse relationship in the distribution of TGF-beta 1 and lymphocyte infiltrates is compatible with a functional relationship between this cytokine and an immune effector cell response to glioblastomas. PMID- 1427756 TI - Lung carcinoma with spindle cell components: sixteen cases examined by immunohistochemistry. AB - Sixteen cases of lung carcinoma with spindle cell components were studied by conventional histochemistry and immunohistochemistry. The epithelial components were squamous cell carcinoma in six cases, adenocarcinoma in four, adenosquamous carcinoma in five, and large cell carcinoma in one. In every case sarcomatous areas were distinctly observed and, in general, neoplastic spindle cells proliferated in close proximity to the epithelial elements. Some of the histochemical procedures suggested mesenchymal features in the stroma of the exophytic portions of three cases, but heterogeneous elements, such as bone or striated muscle, were not observed. By immunohistochemical examination the epithelial elements showed positive reactions for keratin, epithelial membrane antigen, and/or carcinoembryonic antigen to a varying degree according to the histologic types. The spindle cell elements revealed a positive immunoreaction for keratin in all but one case. Epithelial membrane antigen was demonstrated in sarcomatous areas of only five cases and carcinoembryonic antigen was not expressed at all. In contrast, vimentin was distinctly demonstrated in sarcomatous areas of five cases, although other mesenchymal markers, such as desmin, actin, and myosin, were negative. These findings indicate that the spindle cell components in these 16 cases may represent mesenchymal features with partial or complete loss of epithelial features. PMID- 1427757 TI - The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case-control study. AB - Nine morphologic patterns of tumor vessels were identified in eyes removed for ciliary body or choroidal melanoma by the examination of tissue sections stained with fluorescein-conjugated Ulex europaeus I using laser scanning confocal microscopy. This technique also highlights intravascular tumor invasion. Each of these nine morphologic patterns of tumor vessels also may be demonstrated by a modification of the periodic acid-Schiff reaction, viewed with a green narrow band pass filter, but this modified histochemical technique does not accurately identify intravascular tumor invasion. Most tumors have a heterogeneous distribution of vascular patterns. Melanomas in two groups of 20 tumors each were matched by tumor size and location (one group of tumors from patients who survived at least 15 years free of metastatic melanoma after enucleation and one group of tumors from patients who died of metastatic melanoma). A matched case control analysis indicates that the presence of at least one closed vascular loop in a uveal melanoma is the most significant vascular pattern associated with death from metastatic melanoma after enucleation. Closed loops are associated with other histologic features that are predictive of an unfavorable outcome after enucleation: epithelioid cells and mitotic figures. In this preliminary study the formation of closed vascular loops is a marker of tumor progression in ciliary body and choroidal melanomas. PMID- 1427758 TI - Plunging ranula: a case report and a literature review. AB - The plunging ranula is a mucous extravasation cyst of the sublingual gland. It is slightly more common in females, shows no side preference, and is more prevalent in the second and third decades of life. It typically manifests as a painless, nonmobile swelling in the neck and in four of five cases is associated with an intraoral ranula or swelling. If there is no history of an oral ranula the clinical diagnosis is difficult, and it may be left to the reporting pathologist to give the correct diagnosis. The histologic appearance is characteristically of a cyst, devoid of epithelium or endothelium, with a vascular fibro-connective tissue wall containing some chronic inflammatory cells and macrophages stuffed with mucin. The correct diagnosis is essential for the most effective treatment, which is excision of the sublingual gland. PMID- 1427759 TI - Multicystic pancreatic hamartoma: a distinctive lesion with immunohistochemical and ultrastructural study. AB - A multicystic pancreatic hamartoma is reported in a 20-month-old female who presented with abdominal pain and distention. This appears to be a distinctive lesion not previously characterized in the English language literature. The 9-cm mass consisted of large, irregular lobules of well-formed pancreatic acini admixed with fibrous tissue and fat. Cystically dilated ducts of variable caliber lined by benign epithelium were present. Endocrine cell islets were not evident. Immunohistochemistry and ultrastructural examination illustrated insulin producing cells diffusely throughout the exocrine tissue as single cells or in small groups. Cells producing other pancreatic hormones were markedly decreased when compared with an age-matched control pancreas and were similarly dispersed. The patient was alive and well without tumor 9 months later. This entity may provide an unusual opportunity for insight into pancreatic organogenesis and pancreatic cellular differentiation. PMID- 1427760 TI - Autopsies should be required in tissue donation. PMID- 1427761 TI - The manpower shortage: a neophyte's perspective. PMID- 1427762 TI - Estimation of mitotic count in tumors. PMID- 1427763 TI - Epithelial degeneration induced by Helicobacter pylori. PMID- 1427764 TI - Oocyte selection: a new model for the maternal-age dependence of Down syndrome. AB - Previously proposed mechanisms for Down syndrome (trisomy 21) have generally invoked a progressive increase in meiotic nondisjunction to explain maternal-age dependence, but models of this sort have failed to predict the observed patterns of marker segregation. Here we propose instead that age-dependent trisomy 21 results primarily from a mechanism that favors maturation and utilization of euploid oocytes in preference to the pre-existing aneuploid products of mitotic (premeiotic) nondisjunction. The increased utilization of aneuploid oocytes at later stages of maternal life would result from their increased proportion following many progressive cycles of selection against their maturation in earlier stages. Derivation of a quantitative model and evaluation of existing data indicate that the pattern of marker segregation associated with age dependent trisomy 21 supports the proposed mechanism. PMID- 1427765 TI - Mitochondrial gene segregation in mammals: is the bottleneck always narrow? AB - The segregation of a heteroplasmic silent polymorphism in the mitochondrial ND6 gene has been followed in a human maternal lineage comprising eight individuals and spanning three generations. Heteroplasmy persisted in all eight maternally related family members. More importantly, the frequencies of the two alleles showed relatively little variation among individuals or between generations. In contrast to the findings in other mammalian lineages, the present results indicate relatively slow mitochondrial gene segregation. A narrow bottleneck in the number of mitochondrial DNA (mtDNA) molecules, which occurs at some stage of oogenesis, has been advanced to explain rapid mammalian mitochondrial gene segregation. It is suggested here that the segregation of mitochondrial genes may be more complex than initially envisaged, and that models need to be developed that account for both rapid and slow segregation. One possibility, which reconciles both physical and genetic studies of mammalian mtDNA, is that the unit of mitochondrial segregation is the organelle itself, each containing multiple mtDNA molecules. PMID- 1427766 TI - Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA. AB - Direct cDNA sequencing has been performed on asymmetrically amplified transcripts from the human porphobilinogen deaminase gene. Lymphocytes from 30 patients with acute intermittent porphyria were the source of mRNA; of the seven separate point mutations detected, three were silent, whereas four resulted in amino acid changes. Three of these changes involved highly conserved amino acids, and the remaining one a conserved charge. One of these mutations was predicted to cause structural alterations in the protein product. The application of this method to affected families allows the direct identification of these heterogeneous mutations, thus permitting the unequivocal detection of carriers. PMID- 1427767 TI - A minority of 46,XX true hermaphrodites are positive for the Y-DNA sequence including SRY. AB - A total of 30 cases of 46,XX true hermaphroditism was analysed for Y-DNA sequences including the recently cloned gene for male testis-determination SRY. In 3 cases, a portion of the Y chromosome including SRY was present and, in 2 cases, was localised, to Xp22 by in situ hybridisation. Since previous studies have shown that the majority of XX males are generated by an X-Y chromosomal interchange, the Xp22 position of the Yp material suggests that certain cases of hermaphroditism can arise by the same meiotic event. The phenotype in the 3 SRY positive cases may be caused by X-inactivation resulting in somatic mosaicism of testis-determining factor expression giving rise to both testicular and ovarian tissues. Autosomal or X-linked mutation(s) elsewhere in the sex-determining pathway may explain the phenotype observed in the remaining 27 SRY-negative cases. PMID- 1427768 TI - Different chromosomal localization of two adenylyl cyclase genes expressed in human brain. AB - Recently, we characterized a cDNA clone that encodes a human brain adenylyl cyclase (HBAC1). In the present study, we identified a second population of mRNA suspected to encode a new brain adenylyl cyclase (HBA C2). The amino acid sequence of HBA C2 displays significant homology with HBA C1 in the highly conserved adenylyl cyclase domain (250 aminio acids), found in the 3' cytoplasmic domain of all mammalian adenylyl cyclases. However, outside this domain, the homology is extremely low, suggesting that the corresponding mRNA originates from a different gene. We report here the first chromosomal localization of the adenylyl cyclase genes determined by in situ hybridization of human metaphase chromosomal spreads using human brain cDNA probes specific for each mRNA. The probe corresponding to HBA C1 exhibited a strong specific signal on chromosome 8q24, with a major peak in the band q24.2. In contrast, the HBA C2 probe hybridized to chromosome 5p15, with a major peak in the band p15.3. The two cDNAs hybridized at the two loci without any cross reactivity. Thus, in human brain, a heterogeneous population of adenylyl cyclase mRNAs is expressed, and the corresponding genes might be under the control of independent regulatory mechanisms. PMID- 1427769 TI - Commingling and segregation analysis of serum uric acid in five North American populations: the Lipid Research Clinics family study. AB - The role of major genes in the expression of serum uric acid (UA) levels was investigated in data collected from five clinics of the Lipid Research Clinics (LRC) family study. Over 2,000 randomly ascertained individuals were analyzed. The UA distributions were homogeneous among the five LRC clinics and between the parental and offspring generations. This result suggested that the data could be pooled across clinics, thereby increasing the statistical power associated with larger sample sizes for testing various null hypotheses. Additionally, a mixture of three normal distributions best characterized the combined-clinics data. Segregation patterns were examined in the untransformed data, as well as in a more conservative (and biologically meaningful) log transformation. Prior to log transformation, both major and multifactorial effects were detected. The major effect was not transmissible, i.e., was not compatible with Mendelian transmission, and accounted for 39% of the variance in UA levels. However, after the log transform was applied to the data and the segregation analysis was repeated, support for the major effect disappeared altogether and only the multifactorial component remained, accounting for 50% of the variation in offspring and 19% in patients. PMID- 1427770 TI - Molecular genotyping of N-acetylation polymorphism to predict phenotype. AB - N-acetylation polymorphism is one of the representative pharmacogenetic traits that underlie interindividual and interethnic differences in response to xenobiotics. To develop a practical genotyping method to predict acetylator phenotype, we studied the conditions for accurate phenotyping, and identified the phenotype in 51 Japanese. Then we performed Southern blot analysis of genomic DNA from these subjects using 32P-labeled cDNA for polymorphic N-acetyltransferase in the liver, and found that four N-acetyltransferase alleles generated six genotypes. The present genotyping method predicted the rapid, intermediate, and slow acetylators correctly in 48 of 51 overall subjects (96%) and in all of 4 slow acetylators. PMID- 1427771 TI - De novo mutation within the intron-exon junction in the PiZ allele of the alpha-1 antitrypsin gene. AB - A proband homozygous for the PiZ allele of the alpha-1-antitrypsin gene was found to be a heterozygous carrier of the additional nucleotide substitution (C-T) within the intron IV-exon V junction (position 9955 in intron IV, 3 bp upstream of its 3'-splice site). This mutation was not found in DNA from either the PiZ heterozygous parents or the PiZ homozygous brother of proband. PMID- 1427772 TI - Sperm chromosome analysis of two males heterozygous for a t(2;17)(q35;p13) and t(3;8)(p13;p21) reciprocal translocation. AB - Sperm chromosome complements from two males, one heterozygous for the reciprocal translocation t(2;17)(q35;p13) (n = 18) and one for t(3;8) (p13;p21) (n = 73), were analyzed. Only 2:2 segregations were observed with t(2;17): alternate, 56%; adjacent-I, 33%; adjacent-II, 11%. Both 2:2 and 3:1 meiotic segregations occurred in t(3;8): alternate, 34.2%; adjacent-I, 43.8%; adjacent-II, 20.5% and 3:1, 1.4%. A significant excess of chromosomally normal versus balanced sperm complements was observed with both translocation heterozygotes. The frequencies of other chromosome aberrations unrelated to the translocations were 16.7% for t(2;17) and 8.2% for t(3;8). The ratio of X-bearing to Y-bearing sperm was not different from the theoretically expected ratio of 1:1. PMID- 1427773 TI - Mapping of the human COL5A1 gene to chromosome 9q34.3. AB - A 353-bp region encoding for the NH2 terminus of the noncollagenic part of the alpha 1(V) chain was amplified by the polymerase chain reaction (PCR), subcloned and sequenced. The subcloned PCR product (pGC1) presented the same nucleotide sequence as the original fragment from the published sequence of COL5A1. In situ hybridization, using pGC1 as a probe, mapped the COL5A1 gene to chromosome 9q34.3. This assignment shows that COL5A1 is not synthetic with COL5A2, which is localized together with other collagen genes on chromosome 2. PMID- 1427774 TI - Autosomal dominant congenital cataract and microphthalmia associated with a familial t(2;16) translocation. AB - We describe a family in which autosomal dominant congenital cataract and microphthalmia were segregating together with a reciprocal translocation t(2;16) (p22.3;p13.3) through three generations. This family included four individuals with balanced translocations, three with partial trisomy 2p derived from this translocation, and two with a normal karyotype. All of the subjects with balanced and unbalanced translocations had congenital cataract and microphthalmia, whereas the two individuals with normal karyotypes did not show any ocular anomalies. These observations suggest that the altered function of a gene that lies on the 16p13.3 band and that has an important role in the development of the eye is responsible for this disorder. PMID- 1427776 TI - Multiple minute marker chromosomes derived from Y identified by FISH in an intersexual infant. AB - Chromosomal analysis in a child with ambiguous sex showed mosaicism of at least two cell lines with one or more marker chromosomes or none at all. They were shown to be derived from the Y chromosome by fluorescent in situ hybridisation (FISH) using different DNA probes that cover parts of the long and the short arm. PMID- 1427775 TI - Splicing defect of the glycoasparaginase gene in two Japanese siblings with apartylglucosaminuria. AB - Molecular analysis of the glycoasparaginase gene was performed on two Japanese siblings with aspartylglucosaminuria. The cDNA from one patient contained 7 additional bases between exons 3 and 4 (3'-terminal sequence of intron 3). This insertion resulted in a frame shift, and a termination codon appeared at amino acid 146. Amplification and sequencing of genomic DNA detected a single base transition (A-->G) at the 5' side adjacent to the insertion sequence. This mutation created a consensus AG dinucleotide in the splice acceptor site, and produced almost exclusively an abnormal mRNA containing the insertion by alternative splicing. The calculation of the sample score of the acceptor site supported this analytical result. BsmAI restriction site analysis of amplified cDNA and genomic DNA showed that these patients were homozygotes for this mutation. We conclude that the splicing defect in intron 3 causes glycoasparaginase deficiency in these patients. PMID- 1427777 TI - Two new alleles in the tetranucleotide repeat polymorphism at the lipoprotein lipase (LPL) locus. PMID- 1427778 TI - Rearrangements of the X chromosome and Turner syndrome. PMID- 1427779 TI - Huntington disease in black African populations. PMID- 1427780 TI - C-anaphases revised. PMID- 1427781 TI - Chromosome 1 in human colorectal tumors. PMID- 1427782 TI - Premature centromere division. PMID- 1427783 TI - Involvement of 3:1 disjunction in the common reciprocal translocation t(11;22) (q23.3;q11.2) PMID- 1427784 TI - Characterization of hypervariable locus-specific probes derived from a (CAC)5/(GTG)5 multilocus fingerprint in various Eurasian populations. AB - Population genetic studies were performed using oligonucleotide probes (Hz1103, Hz4103, and Hz4201) that recognize three hypervariable loci (D11S859, D9S128 and D22S265) in the human genome. DNA from 17 Eurasian population samples including 37 monozygotic twin pairs were digested with HinfI and hybridized with Hz4103. Allele frequency distribution profiles and high degrees of heterozygosity were similar in each ethnic group. Among 804 unrelated individuals tested, we detected one case of mosaicism caused by a somatic recombination event in a monozygotic twin. In addition, samples of DNA from three ethnic groups (Germans, Assamese Hindus and Thais) and from German and Thai families were restricted with MboI and probed with Hz1103, Hz4103, and Hz4201. The results showed considerable degrees of heterozygosity and locus-specific allele distribution profiles, rather than interpopulation differences. Among 262 meioses (12 three-generation families with a total of 131 children) analyzed, a single recombination event was observed following hybridization with the DNA probe Hz4201. PMID- 1427785 TI - Prenatal diagnosis of Duchenne muscular dystrophy by fetal muscle biopsy. AB - Prenatal diagnosis and carrier detection for Duchenne muscular dystrophy (DMD) usually can be performed using DNA analysis. When recombination occurs within the DMD gene, or DNA analysis is uninformative, or in pedigrees where it is unclear whether or not the consultand is a carrier, direct examination of muscle by dystrophin analysis may provide the only means of prenatal diagnosis. We present three cases representing each of these molecular genetic diagnostic dilemmas. In each instance, we used sonographically guided fetal muscle biopsy for dystrophin protein analysis to resolve the dilemma. In the first and third cases, the presence of normal dystrophin was shown by immunofluorescence and this was followed by delivery of an unaffected male fetus. In the second case, dystrophin was not found in fetal muscle tissue implying that this fetus was affected. The absence of dystrophin and affected status was confirmed in skeletal and cardiac muscle obtained after pregnancy termination. PMID- 1427786 TI - The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences. AB - A total of 101 different examples of point mutations, which lie in the vicinity of mRNA splice junctions, and which have been held to be responsible for a human genetic disease by altering the accuracy of efficiency of mRNA splicing, have been collated. These data comprise 62 mutations at 5' splice sites, 26 at 3' splice sites and 13 that result in the creation of novel splice sites. It is estimated that up to 15% of all point mutations causing human genetic disease result in an mRNA splicing defect. Of the 5' splice site mutations, 60% involved the invariant GT dinucleotide; mutations were found to be non-randomly distributed with an excess over expectation at positions +1 and +2, and apparent deficiencies at positions -1 and -2. Of the 3' splice site mutations, 87% involved the invariant AG dinucleotide; an excess of mutations over expectation was noted at position -2. This non-randomness of mutation reflects the evolutionary conservation apparent in splice site consensus sequences drawn up previously from primate genes, and is most probably attributable to detection bias resulting from the differing phenotypic severity of specific lesions. The spectrum of point mutations was also drastically skewed: purines were significantly over-represented as substituting nucleotides, perhaps because of steric hindrance (e.g. in U1 snRNA binding at 5' splice sites). Furthermore, splice sites affected by point mutations resulting in human genetic disease were markedly different from the splice site consensus sequences. When similarity was quantified by a 'consensus value', both extremely low and extremely high values were notably absent from the wild-type sequences of the mutated splice sites. Splice sites of intermediate similarity to the consensus sequence may thus be more prone to the deleterious effects of mutation. Regarding the phenotypic effects of mutations on mRNA splicing, exon skipping occurred more frequently than cryptic splice site usage. Evidence is presented that indicates that, at least for 5' splice site mutations, cryptic splice site usage is favoured under conditions where (1) a number of such sites are present in the immediate vicinity and (2) these sites exhibit sufficient homology to the splice site consensus sequence for them to be able to compete successfully with the mutated splice site. The novel concept of a "potential for cryptic splice site usage" value was introduced in order to quantify these characteristics, and to predict the relative proportion of exon skipping vs cryptic splice site utilization consequent to the introduction of a mutation at a normal splice site. PMID- 1427788 TI - Detection of GST1 gene deletion by the polymerase chain reaction and its possible correlation with stomach cancer in Japanese. AB - A homozygous gene deletion at the GST1 locus of genomic DNA isolated from peripheral blood was investigated for its relationship with several types of cancer using the polymerase chain reaction (PCR) technique. DNA samples were prepared from blood obtained from 128 healthy blood donors and 150 patients with cancer or chronic hepatitis. PCR primers were prepared based on the human cDNA sequence and the intron/exon sequences of the rat Yb2 gene. The amplified sequence between exons 5 and 6 including intron 5 showed very clearly the presence of absence of the GST1 gene, after electrophoresis in a 2% agarose gel. Segregation of the presence and absence of PCR product from samples of twins and their parents indicated that presence involves homozygous or heterozygous normal GST1 genotypes while absence involves only homozygous gene deletion. The patients with stomach cancer had a significantly higher frequency of gene deletion than did the healthy controls (P < 0.005). Thus, GST1 deletion may be a possible genetic marker for early detection of a group at high risk of stomach cancer. PMID- 1427787 TI - Polymerase chain reaction analysis of fragile X mutations. AB - The mutation that underlies the fragile X syndrome is presumed to be a large expansion in the number of CGG repeats within the gene FMR-1. The unusually GC rich composition of the expanded region has impeded attempts to amplify it by the polymerase chain reaction (PCR). We have developed a PCR protocol that successfully amplifies the (CGG)n region in normal, carrier and affected individuals. The PCR analysis of several large fragile X families is presented. The PCR results agree with those obtained by direct genomic Southern blot analyses. These favorable comparisons suggest that the PCR assay may be suitable for rapid testing for fragile X mutations and premutations and genetic screening of at-risk individuals. PMID- 1427789 TI - Molecular genetic analysis of 67 patients with Duchenne/Becker muscular dystrophy. AB - A total of 56 Duchenne muscular dystrophy (DMD) patients and 11 Becker muscular dystrophy (BMD) patients was analyzed by extended "multiplex" amplification of the DMD/BMD gene; deletions were found in 60% of these patients. The data obtained were used to test the frameshift hypothesis and to compare the distribution of familial versus isolated cases. A significant correlation was found between deletions and isolated cases. Additional experiments were performed in order to determine the deletion breakpoints more precisely. These data are a prerequisite for carrier analysis in the respective families by detection or exclusion of aberrant cDNA fragments derived from ectopic lymphocyte RNA. This diagnostic technique is illustrated by 5 examples. PMID- 1427791 TI - Significance of the clonal and sporadic chromosome abnormalities in non neoplastic renal tissue. AB - Trisomy 7, trisomy 10 and loss of the Y chromosome have been found by some authors in presumptive normal parts of human kidneys. We describe cytogenetic findings in short-term cultures from 58 biopsies obtained from non-neoplastic and neoplastic (renal cell carcinoma, RCC) tissues from the same kidney, the same types of tissues from independent kidneys, and tissue from kidneys without neoplasia. The results indicate the following. Non-neoplastic tissue from kidneys involved in RCC have (in mosaics) trisomies 5, 7, 10, 18 and loss of the Y as non random clonal changes. They are not the result of local metastasis but are also found in kidneys with non-tumoral chronic pathologies and should thus not be considered specific for RCC. They are neither culturing artefacts nor a general phenomenon found in cultured normal solid tissues, but are acquired abnormalities, possibly related to various reactive cellular states in the tissues that are histologically normal. PMID- 1427790 TI - Plasminogen with type-I mutation is polymorphic in the Japanese population. AB - A functionally inactive plasminogen (PLG) variant designated as PLG M5 is polymorphic in the Japanese population and has a feature common to PLG with type I mutation that has a codon 601 missense mutation in exon 15 (GCT for Ala-->ACT for Thr). This study was conducted to clarify whether the type-I mutation of PLG is present in PLG M5 and polymorphic in the Japanese population. Direct sequencing of the amplified DNA from the PLG gene in a heterozygote for PLG M5 revealed that the sequence of the exon 15 in the gene for PLG M5 is identical with that in the PLG gene with type-I mutation. In addition, the amplified DNA from the PLG gene in 12 heterozygotes for PLG M5 reacted with the probe for the type-I mutation in dot blot hybridization with an allele-specific oligonucleotide probe. The heterozygote for PLG with type-I mutation was found in 2.2% of 360 unrelated healthy subjects. These data indicate that the type-I mutation of PLG is present in PLG M5 and polymorphic in the Japanese population. The data also suggest that the PLG M5 is identical with PLG Tochigi and Kagoshima. PMID- 1427792 TI - The murine Rb(6.16) translocation: alterations in the proportion of alternate sperm segregants effecting fertilization in vitro and in vivo. AB - The segregation products of the mouse Rb-(6.16)24 Lub male translocation carrier were analyzed at first cleavage metaphase to determine whether the proportion of normal, balanced, and unbalanced sperm segregants differ in fertilizations occurring in vivo and in vitro. From 34 males, the sperm genomes in 268 first cleavage mouse embryos were analyzed cytogenetically: 137 and 131 following in vivo and in vitro fertilization, respectively. Both systems demonstrated a preponderance of alternate (67.2% and 54.2%) as compared to adjacent segregation (10.2% and 13.7% as estimated). A contingency table showed that the distribution of reciprocal alternate segregants differed significantly between the two fertilization environments (chi 2 = 20.64, P < 0.0005). Whereas chromosomally normal sperm were 3.6 times more likely than the balanced reciprocals to fertilize in vivo (78.3% normal: 21.7% balanced), 1:1 ratios were recovered following in vitro fertilization (43.7% normal: 56.3% balanced). The data also showed an excess of Y-bearing sperm with the translocation in both in vivo and in vitro fertilization groups. In the latter these segregants were 3 times more likely than X-bearing ones to effect fertilization. These data suggest a phenotypic disadvantage of translocation-X-bearing sperm, possibly mediated through altered haploid gene expression on chromosome 6 and gene expression on the Y. The results show clear evidence for prezygotic selection in vivo and indicate that the environment in which fertilization occurs significantly affects the transmission frequency of this specific translocation. PMID- 1427793 TI - Variable number of tandem repeat (VNTR) polymorphism at locus D17S5 (YNZ22) in four ethnically defined human populations. AB - We have analyzed the hypervariable locus D17S5 in four well-defined human populations (Kachari of Northeast India; Dogrib Indian of Canada; New Guinea Highlander of Papua New Guinea; and a relatively homogeneous Caucasian population of North German extraction) using both Southern blot analysis and the polymerase chain reaction (PCR) technique to: (1) compare the efficiency and limitation of Southern blotting versus PCR-based techniques in genotyping variable number of tandem repeat loci, and (2) provide allele frequency data at this locus in these four anthropologically defined populations. Preferential PCR amplification of smaller alleles associated with D17S5 was corrected by lowering the DNA template concentration to 200 ng, and by reducing the extension time to 2 min. A perfect correspondence was observed between the results from Southern blot and PCR analysis in all but one sample. A very large allele, of approximately 24 to 25 repeat units, detected by Southern blotting, could not be amplified by PCR, resulting in an incorrect genotyping rate of less than 0.5%. Considering the grave consequences of mistyping in forensic and paternity testing, it is suggested that heterozygous controls consisting of large and small alleles should be employed in each PCR experiment, and PCR-generated homozygotes should be confirmed by Southern blotting. Significant variation in the number and frequency of alleles at this locus was observed in the four examined populations. A total of 15 different alleles were detected. The average heterozygosity varied from 54% in the Dogrib to 89% in the Kachari. No heterozygote deficiency was observed at this locus in any of the examined populations. PMID- 1427794 TI - A genetic model for the Prader-Willi syndrome and its implication for Angelman syndrome. AB - Sporadic cases of Prader-Willi syndrome (PWS) are associated with the physical absence of the paternal Prader-Willi chromosome region (PWCR) by deletion 15q11 13, by segmental maternal heterodisomy or by chromosome rearrangements resulting in homozygosity for maternal PWCR. In isolated/familial cases, it is proposed that the expression of PWS depends on the functional absence caused by mutated gene(s) within the paternal PWCR. The same mutation on a maternally derived chromosome 15 is not able to express PWS. An epigenetic mechanism associated with the paternal meiosis is essential. In the Angelman syndrome (AS), inverse mechanisms are postulated. There is convincing evidence for specific PWS and AS genes or alleles within PWCR. This is compatible with the observations of interstitial chromosome deletions of the critical region in normal individuals or in probands with phenotypes other than PWS or AS. The new ideas of the model stated here are: (1) the proposed epigenetic mechanism in PWCR is obviously common in humans, but is usually of no phenotypic relevance; (2) interactions with specific chromosomal or gene mutations are required for the clinical expression of PWS or AS; (3) each factor alone is not able to produce an abnormal phenotype. PMID- 1427795 TI - A genetic study of the human low-voltage electroencephalogram. AB - The studied phenotype, the low-voltage electroencephalogram (LVEEG), is characterized by the absence of an alpha rhythm from the resting EEG. In previous studies, evidence was found for a simple autosomal-dominant mode of inheritance of the LVEEG. Such a polymorphism in brain function can be used as a research model for the stepwise elucidation of the molecular mechanism involved in those aspects of neuronal activity that are reflected in the EEG. Linkage with the variable number of tandem repeats (VNTR) marker CMM6 (D20S19) and localization of an LVEEG (EEGV1) gene on 20q have previously been reported, and genetic heterogeneity has been demonstrated. This latter result has been corroborated by studying new marker (MS214). The phenotype of the LVEEG is described here in greater detail. Its main characteristic is the absence of rhythmic alpha activity, especially in occipital leads, whereas other wave forms such as beta or theta waves may be present. Analysis of 17 new families (some of them large), together with 60 previously described nuclear families, supports the genetic hypothesis of an autosomal-dominant mode of inheritance. Problems connected with the analysis of linkage heterogeneity, exclusion mapping, and the study of multipoint linkage are discussed. A possible explanation of the localization of LVEEG in the close vicinity of another gene influencing synchronization of the normal EEG, the gene for benign neonatal epilepsie, is given. PMID- 1427796 TI - Sexually transmitted diseases in children: HIV infection. PMID- 1427797 TI - Criteria for early congenital syphilis--a perspective from Africa. PMID- 1427798 TI - Factors associated with pediculosis pubis and scabies. AB - OBJECTIVE: To ascertain factors associated with genital pediculosis and scabies infestations among attenders at an STD clinic. DESIGN: Cross sectional assessment of potential risk factors by multiple logistic regression. SETTING: A central city sexually transmitted diseases (STD) clinic in Adelaide, South Australia. SUBJECTS: All men and women patients attending from 1988 to 1991. RESULTS: Pediculosis pubis was diagnosed in 205 of 12,170 (1.7%) men and 65 (1.1%) of 6125 women, and scabies in 56 (0.5%) men and 6 (0.1%) women attending an STD clinic from 1988-1991. Independent risk factors by multivariate analysis for pediculosis pubis in women were pregnancy (odds ratio (OR) = 2.3), sex outside the state (OR = 2.2) and age under 25 (OR = 2.0). Many factors were associated with pediculosis pubis in men, including no steady partner (OR = 1.4), multiple partners (OR = 1.6), being unmarried (OR = 2.0) and homosexual behaviour (OR = 1.6). None of these factors was associated with scabies infestation which was strongly associated with being Aboriginal (OR = 6.8) and being unemployed (OR = 2.5). CONCLUSION: In this setting scabies appears to be determined by socioeconomic factors and pediculosis pubis predominantly by sexual activity factors. PMID- 1427799 TI - Sexual behaviour of women attending an inner-city STD clinic before and after a general campaign for safer sex in Denmark. AB - OBJECTIVES: To examine the sexual behaviour and the prevalence of sexually transmitted diseases (STD) among females attending an inner-city STD clinic before and after safer sex campaigns. SUBJECTS: In 1984 981 women and in 1988 684 women were interviewed immediately after the venerological examination. SETTING: Department of Dermato-Venereology, Bispebjerg Hospital, Copenhagen, Denmark. METHODS: In a face to face interview, details of symptoms, age at coitarche, number of sexual partners (lifetime and during the last year), obstetric history, and contraceptive methods were recorded. RESULTS: A substantially higher proportion of women used condoms in 1988 than in 1984. A dramatic decrease in the prevalence of gonorrhoea occurred (from 22% in 1984 to 6% in 1988, p < 0.01), whereas an increase in the number of patients with genital warts was observed (from 4% in 1984 to 10% in 1988, p < 0.05). The prevalence of chlamydia, genital herpes, and cervical dysplasia remained unchanged. No significant changes in the number of sexual partners, or the frequency of sexual intercourse or unplanned pregnancy could be detected from 1984 to 1988. CONCLUSIONS: The safer sex campaigns have only been partly successful, as a general reduction in all sexually transmitted diseases should be expected as a result of the increased use of condoms. Future campaigns should focus on the correct use of condoms, and encourage a lifestyle with stable sexual relationship. PMID- 1427800 TI - A colposcopic case-control study of cervical squamous intraepithelial lesions in women with anogenital warts. AB - OBJECTIVE: To assess whether anogenital warts, present or past, are an indication for women to be referred for colposcopy. DESIGN: A case control study comparing patients with and without a history of anogenital warts. SETTING: A department of genitourinary medicine in West London. PATIENTS: 468 patients examined by colposcopy between January 1985 and December 1987 of whom 147 (31%) had abnormal cytology, 163 (35%) had anogenital warts and 158 (34%) had both. MAIN OUTCOME MEASURES: Colposcopic findings and histology of cervical biopsies compared with behavioural and disease variables. RESULTS: Human papillomavirus infection (HPVI) of the cervix showed no relationship with a life time history of vulval warts, or with the presence of anogenital warts on clinical examination, or with any parameter of sexual behaviour included in the study. Cervical intraepithelial neoplasia (CIN) was strongly associated with current IUCD usage (RR = 7.75) and coitarche under 16 years of age (RR = 3.72), but a history of vulval warts yielded a negative association (RR = 0.34), suggesting a protective effect. This relationship held true when cytological dyskaryosis was made the dependent variable (RR = 0.24). CONCLUSIONS: Anogenital warts are not a risk for subclinical cervical HPVI or for CIN and therefore not an indication for colposcopy. PMID- 1427801 TI - The association between sexually transmitted diseases and inflammatory cervical cytology. AB - OBJECTIVES: To assess the significance of inflammatory changes as a marker of sexually transmitted diseases and their use as a diagnostic aid. METHODS: 363 patients attending a department of genito urinary medicine were examined prospectively. All underwent cervical cytology and full STD screening. Cervical cytology was assessed for evidence of the presence or absence of inflammatory changes. RESULTS: There was no significant association between inflammatory cytology and cervical ectropion or dyskaryosis. Infections with Chlamydia trachomatis and Trichomonas vaginalis were significantly associated with inflammatory changes but there was no significant association with chlamydia alone, and 91.1% of T. vaginalis infections were detected on cytology. CONCLUSION: The presence of inflammatory changes on cervical cytology seems a poor indicator of sexually transmitted diseases. PMID- 1427802 TI - The management of subclinical wart virus infection of the cervix in a genitourinary clinic. AB - OBJECTIVE: To assess whether cold coagulation to the cervix eliminates subclinical wart virus infection and to determine the effectiveness of treatment for CIN I and II, using cold coagulation, by genitourinary physicians. DESIGN: Prospective study. SETTING: Department of Genitourinary medicine in a large teaching hospital. PARTICIPANTS: All patients who received cold coagulation to the cervix in a 1 year period, who had not had previous treatment. RESULTS: 261 patients were enrolled into this study; of these, 138 (53%) patients attended for repeat colposcopy and cytology at one year. Cure rates for lesions were 66% for initial wart virus infection, 80% for CIN I and 94% for CIN II and III. Four (5%) cases in whom repeat cytology was normal had CIN which would have been missed if repeat colposcopy had not been performed at one year. CONCLUSIONS: Cold coagulation is inappropriate treatment for subclinical wart virus infection of the cervix but is useful for the management of patients with CIN. Repeat colposcopy following treatment to the cervix is not necessary if cervical cytology is normal. PMID- 1427803 TI - HIV infection among heterosexual travellers attending the Hospital for Tropical Diseases, London. AB - OBJECTIVE: To determine the prevalence of HIV infection in travellers attending the Hospital for Tropical Diseases, London, and to assess correlates and behavioural risk factors for infection. DESIGN: All patients tested for HIV infection during a 28-month period were included. Information was obtained from clinical records and standardised serological request forms. SETTING: Hospital for Tropical Diseases, London, UK. SUBJECTS: 298 patients (in-patient and out patient) were tested. RESULTS: 258 of those tested were exclusively heterosexual and not injecting drug users. 5.4% of these were HIV-1 antibody positive. Rates in those originating from the UK and those from outside the UK were 1.8% and 33.2% respectively. Most non-UK citizens were symptomatic when tested; UK citizens were generally tested as part of a routine screening, therefore the two groups are not comparable. Rates of risk behaviour were high in both groups. CONCLUSION: The rate of HIV infection in heterosexual travellers was 5.4%. Amongst UK citizens the rate was 1.8%. All travellers should be made aware of the potential risk of acquiring HIV infection through sexual contact. PMID- 1427804 TI - Comparison of fleroxacin and penicillin G plus probenecid in the treatment of acute uncomplicated gonococcal infections. AB - OBJECTIVE: To investigate the activity of fleroxacin in acute uncomplicated infections with N. gonorrhoeae in comparison with conventional penicillin G plus probenecid treatment. DESIGN: Multicentre open label randomised parallel group study. SUBJECTS: Male patients aged 18 years or over from university departments of urology, epidemiology and dermatology and a clinic for sexually transmitted diseases. INTERVENTIONS: Two hundred and sixty male patients were randomly assigned to treatment with either a single oral dose of fleroxacin 400 mg (130 patients) or a single intramuscular dose of penicillin G (2.4 or 5.0 mega units) plus a single oral dose of probenecid 1 gram (130 patients). Efficacy and safety assessments were undertaken at follow-up (3-14 days after treatment). Efficacy was assessed as bacteriological outcome of treatment. Safety was assessed by evaluation of adverse events, laboratory abnormalities and changes in vital signs. RESULTS: Two hundred and twenty four patients (114 in the fleroxacin group and 110 in the penicillin plus probenecid group) were evaluated for efficacy. Bacteriological cures were achieved in 100% of patients in the fleroxacin group and 97% of patients in the penicillin plus probenecid group. There was no statistically significant difference between the two groups in this respect (Fisher exact test, p = 0.25). Clinical cures were achieved in 100% of patients receiving fleroxacin and 95% of patients receiving penicillin plus probenecid. Safety analyses were undertaken on 255 patients (126 in the fleroxacin group and 129 in the penicillin plus probenecid group). No adverse events were reported for either treatment group, and no clinically relevant laboratory abnormalities were apparent. Thus, there appeared to be no difference in the efficacy or safety of these two treatments when used to treat acute, uncomplicated urethral gonorrhoea in males. CONCLUSIONS: In this study fleroxacin proved to be highly effective therapy for uncomplicated gonococcal urethritis in males and may provide a favourable alternative to standard treatment. PMID- 1427805 TI - Antibiotic susceptibilities, serotypes and auxotypes of Neisseria gonorrhoeae isolated in New Zealand. AB - OBJECTIVE: The aim of the study was to determine the distribution of auxotypes and serotypes and the prevalence of antibiotic resistance among New Zealand isolates of Neisseria gonorrhoeae. MATERIALS AND METHODS: A total of 486 gonococci isolated in 1988 were auxotyped, serotyped, and tested for susceptibilities to ten antibiotics. RESULTS: The gonococci were susceptible to all the antibiotics tested except penicillin and tetracycline. Eleven (2.2%) produced beta-lactamase, one (0.2%) showed chromosomal penicillin resistance, and 18 (3.7%) were resistant to a low-level of tetracycline. Most of the gonococci belonged to six auxotypes. The three predominant auxotypes were arginine requiring (Arg-), non-requiring (NR), and arginine, hypoxanthine, uracil requiring (AHU-). The majority of the isolates belonged to serogroup IB and to six serovars. The most prevalent serovars were IB-3 and IB-1. There was an association between penicillin susceptibility and auxotype or serovar among non penicillinase producing N. gonorrhoeae (PPNG) isolates. CONCLUSIONS: Antibiotic resistance, including penicillin resistance, remains uncommon among gonococci in New Zealand. Baselines have been established for future epidemiological studies using both auxotyping and serotyping. PMID- 1427806 TI - A clinical evaluation of trichomoniasis in San Jose, Costa Rica using the InPouch TV test. AB - OBJECTIVE: to determine the prevalence of trichomoniasis in San Jose, Costa Rica, comparing two methods, the InPouch TV test and the saline wet mount. METHODS: One hundred symptomatic and asymptomatic female patients at two hospitals and at a sexually transmitted disease (STD) clinic were evaluated. Vaginal discharge was the most prevalent genitourinary abnormality among symptomatic patients. The patients were between 18 and 70 years old. Fifty-seven were from the STD clinic, 43 from the two hospitals. A saline wet mount and a culture were taken from each patient. The culture employed a new procedure for diagnosis of trichomonads, the InPouch TV test (BioMed Diagnostics, San Jose, CA). RESULTS: Thirteen of the 100 patients were culture positive, two of whom were wet mount positive. No wet mount positives were culture negative. Eleven of the positive tests were from the STD clinic and two were from the hospitals. CONCLUSIONS: The results of this initial epidemiologic study indicate a prevalence of 19% for trichomoniasis in the STD clinic population and 4.6% in the hospitals group. Trichomonas vaginalis was not diagnosed by laboratory methods prior to this study. The InPouch TV test has a selective fungicidal and bactericidal, enriched proteose-peptone medium which provides a sensitivity of 4 organisms per ml and a 1 year shelf life at room temperature. This in vitro culture test demonstrated unique capabilities as a transport and culture medium. Its procedure offers simplicity in application and an excellent visualisation of trichomonads. PMID- 1427807 TI - A case report of lymphangioma circumscriptum of the vulva. PMID- 1427808 TI - Amyloid tumour of the urethra presenting as non-specific urethritis. AB - Amyloid tumour involving the urethra is a well recognised but rare occurrence. Chronic inflammation secondary to gonococcal urethritis is thought to be a possible predisposing factor. We report the case of a young man who presented with non-gonococcal urethritis and haematuria and was subsequently found to have primary amyloid of the urethra. PMID- 1427809 TI - An unusual foreign body in the preputial sac. AB - A 28 year old Indian male presented with an unusual foreign body, a penicillin bottle containing tincture of iodine, in the preputial sac. The purpose of introducing the bottle was to tickle his glans penis as a form of masturbation. The bottle was so firmly impacted that it could be removed only under general anaesthesia. PMID- 1427810 TI - Hepatitis-B virus infection in sexually transmitted disease clinic attenders in an African city, (Jos, Nigeria) PMID- 1427811 TI - Malignant syphilis in a teenage girl. PMID- 1427812 TI - An increase in pharyngeal gonorrhoea: cause for concern regarding HIV infection. PMID- 1427813 TI - Screening for asymptomatic Chlamydia trachomatis infection in adolescent men by examination of voided urine. PMID- 1427814 TI - Determinants of hepatitis B virus surface antigen positivity in adults attending sexually transmitted disease clinics in Italy. PMID- 1427815 TI - Emerging incidence of vulval intraepithelial neoplasia in young women with genital warts. PMID- 1427816 TI - Prodromal symptoms in genital herpes simplex infection. PMID- 1427817 TI - Variations in alphoid DNA sequences escape detection of aneuploidy at interphase by FISH technique. AB - The advent of a new staining technique, termed fluorescence in situ hybridization (FISH), allows the rapid identification of the genomic constitution of an individual with aneuploidy even in interphase nuclei through the use of a series of chromosome-specific DNA probes, an approach termed "interphase cytogenetics." However, alphoid DNA sequences of every centromere are polymorphic (heteromorphic), and the number of targeted sequences may be below the detection level of a specific DNA probe, thus escaping detection and resulting in the imprecise identification of the chromosomal constitution at interphase. The limitations associated with the FISH technique have dire consequences which are emphasized here with an example in which the presence of an additional chromosome 21 in two siblings born consecutively with trisomy 21 (Down syndrome) was not detected by "interphase cytogenetics." The copy number of alphoid DNA sequences of one of the paternal chromosomes 21 was low and resulted in discordance between domain numbers at interphase and actual chromosome numbers at metaphase in both children. This is an isolated incident that could have led to a misdiagnosis if FISH were the only test employed. Although the advantages of this technology are undeniably enormous, the present finding has made it apparent that precise standards and reliability of the procedure must be established prior to its routine application. PMID- 1427818 TI - A physical map of a 1.3-Mb region on the long arm of chromosome 12, spanning the GLI and LRP loci. AB - We have used pulsed-field gel electrophoresis to construct a long-range restriction map spanning more than 1.3 million bp of the q13-q14 segment of chromosome 12. Within this region lie the genes coding for the gli oncogene and the low-density lipoprotein receptor-related protein (LRP). The distance between the genes is about 200-300 kb. We also observe a methylation-free island 3' to the LRP gene. PMID- 1427819 TI - The CCAAT/enhancer binding protein (C/EBP alpha) gene (CEBPA) maps to human chromosome 19q13.1 and the related nuclear factor NF-IL6 (C/EBP beta) gene (CEBPB) maps to human chromosome 20q13.1. AB - The CEBPA gene encoding CCAAT/enhancer binding protein (C/EBP alpha) has been mapped to human chromosome 19 and the CEBPB (formerly TCF5) gene encoding NF-IL6 (C/EBP beta) to human chromosome 20 by Southern blot analysis of Chinese hamster x human and mouse x human somatic cell hybrids. CEBPA has been further mapped to 19q13.1 between the loci GPI and TGFB using human x hamster somatic cell hybrids containing restricted fragments of human chromosome 19. This position was confirmed by fluorescence in situ hybridization. Furthermore, CEBPB has been mapped to 20q13.1 by fluorescence in situ hybridization. PMID- 1427820 TI - Synteny mapping in the bovine: genes from human chromosome 4. AB - Genes homologous to those located on human chromosome 4 (HSA4) were mapped in the bovine to determine regions of syntenic conservation among humans, mice, and cattle. Previous studies have shown that two homologs of genes on HSA4, PGM2 and PEPS, are located in bovine syntenic group U15 (chromosome 6). The homologous mouse genes, Pgm-1 and Pep-7, are on MMU5. Using a panel of bovine x hamster hybrid somatic cells, we have assigned homologs of 11 additional HSA4 loci to their respective bovine syntenic groups. D4S43, D4S10, QDPR, IGJ, ADH2, KIT, and IF were assigned to syntenic group U15. This syntenic arrangement is not conserved in the mouse, where D4s43, D4s10, Qdpr, and Igj are on MMU5 while Adh-2 is on MMU3. IL-2, FGB, FGG, and F11, which also reside on MMU3, were assigned to bovine syntenic group U23. These data suggest that breaks and/or fusions of ancestral chromosomes carrying these genes occurred at different places during the evolution of humans, cattle, and mice. PMID- 1427821 TI - Human chromosome 8 linkage map based on short tandem repeat polymorphisms: effect of genotyping errors. AB - A linkage map consisting of 21 dinucleotide repeat polymorphisms, 1 tetranucleotide repeat polymorphism, and 3 RFLPs was constructed for human chromosome 8. The map spanned most of the chromosome length from near pter to q23 q24 on the distal portion of the long arm. The total 186 cM length of the female map was over two times the 84 cM length of the male map. Cytogenetic mapping of the polymorphisms using a panel of hybrids containing rearranged chromosomes was completely consistent with the linkage map. Special effort was made to remove as many genotyping errors, including parental phase errors, as possible. Removal of errors, in agreement with recent theoretical predictions, led to reduction of the total length of the sex-equal map by 10% from 145 to 130 cM. PMID- 1427822 TI - Chromosomal mapping of the human (MACS) and mouse (Macs) genes encoding the MARCKS protein. AB - The myristoylated, alanine-rich C-kinase substrate, or MARCKS protein, is a major cellular substrate for protein kinase C that is also a high-affinity calmodulin binding protein. In addition, it is the prototype of a small family of myristoylated, calmodulin-binding protein kinase C substrate proteins. We isolated a phage clone from a mouse genomic library that spanned the entire coding sequence of the mouse MARCKS protein. The first 612 bp of the putative promoter was 89% identical to a corresponding region of the human promoter, and contained at least 59 potential transcription factor binding sites in analogous locations; both human and mouse promoters lacked TATA boxes. The mouse genomic probe was used to localize the mouse gene to chromosome 10, in the middle of a linkage group that corresponds to a region on human chromosome 6q. These data strongly suggested that the human gene would localize to 6q21. This was confirmed by studies of DNA from a patient with del(6)(q21), in which expression of the human gene encoding MARCKS, MACS, was only about 50% of normal; MARCKS mRNA expression in lymphoblast RNA from this patient was only 22% of normal. These studies confirm that the mouse and human MARCKS proteins are products of the same genes in their respective species; differences in their primary sequence can therefore be attributed to species variation rather than to the existence of related genes. PMID- 1427824 TI - A contig assembly program based on sensitive detection of fragment overlaps. AB - An effective computer program for assembling DNA fragments, the contig assembly program (CAP), has been developed. In the CAP program, a filter is used to eliminate quickly fragment pairs that could not possibly overlap, a dynamic programming algorithm is applied to compute the maximal-scoring overlapping alignment between each remaining pair of fragments, and a simple greedy approach is employed to assemble fragments in order of alignment scores. To identify the true fragment overlaps, the dynamic programming algorithm uses specially chosen sets of alignment parameters to tolerate sequencing errors and to penalize "mutational" changes between different copies of a repetitive sequence. The performance tests of the program on fragment data from genomic sequencing projects produced satisfactory results. The CAP program is efficient in computer time and memory; it took about 4 h to assemble a set of 1015 fragments into long contigs on a Sun workstation. PMID- 1427823 TI - Molecular cloning and chromosomal mapping of a cDNA encoding human 80K-L protein: major substrate for protein kinase C. AB - We have isolated and sequenced complementary DNA (cDNA) for the human 80K-L protein, a major substrate for protein kinase C and the human homologue of an 80- to 87-kDa bovine protein named MARCKS (myristoylated alanine-rich C kinase substrate). The human 80K-L cDNA encodes a protein of 332 amino acids with a calculated molecular weight of 31,534. Homology comparisons of the nucleotide sequences of the cDNAs indicated that their 3'-untranslated regions are more homologous than the coding regions. Spot blot hybridization using flow-sorted human chromosomes indicated that the gene encoding the 80K-L protein, designated MACS, maps to the q15----qter region of human chromosome 6, and it also suggested that a genomic region with a sequence homologous to the 3'-untranslated region of the 80K-L mRNA exists on chromosome 21. PMID- 1427825 TI - Chromosomal assignment of human YAC clones by fluorescence in situ hybridization: use of single-yeast-colony PCR and multiple labeling. AB - Alu-PCR provides a convenient tool for amplification of human-specific sequences from yeast DNA containing yeast artificial chromosomes (YAC) clones. PCR products can be labeled nonisotopically and hybridized in situ, and the chromosomal origin of the clones can be determined. This avoids time-consuming gel purification of the yeast artificial chromosome and the low-efficiency procedure of labeling whole yeast DNA containing the YAC. The application of Alu-PCR to single-yeast colonies permits the mapping of YACs at a very early stage of their characterization. In situ hybridization can detect clones with noncontiguous fragments of DNA, and these can be discarded without further time-consuming characterization. To increase further the potential of the method, we show the application of multicolor hybridization techniques. PMID- 1427826 TI - Linkage study of chronic childhood-onset spinal muscular atrophy (SMA): confirmation of close linkage to D5S39 in French Canadian families. AB - Chronic childhood-onset spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy, the most common neuromuscular disorder in childhood. Recent linkage analyses have mapped this disease to 5q12-5q14. We show that chronic SMA (Types II and III) is tightly linked to the marker locus D5S39 (Zmax = 5.47 at theta = 0.02) in eight French Canadian families. In contrast to previously published results, we do not observe close linkage between chronic SMA and D5S6 (Zmax = 0.34 at theta = 0.18) or D5S78 (Zmax = 0.25 at theta = 0.21). Last, we present a family that appears to be discordant for this localization but may represent the first example of an incompletely penetrant individual. PMID- 1427827 TI - Exclusion of chromosome 6 and 8 locations in nonrhodopsin autosomal dominant retinitis pigmentosa families: further locus heterogeneity in adRP. AB - Genetic studies have revealed that 25 to 30% of autosomal dominant retinitis pigmentosa (adRP) families have mutations in the rhodopsin gene, while the remainder do not. More recently linkage data and mutation detection have demonstrated two further loci implicated in adRP, at an as yet unidentified gene on chromosome 8p and at the human gene homologue of the mouse Rds (Retinal Degeneration Slow) gene on chromosome 6p. We have previously reported exclusion of adRP from the rhodopsin locus on 3q in two large adRP families. We now report exclusion data for both families, on chromosomes 6 and 8, demonstrating that the adRP phenotype results from mutations in at least four locations. PMID- 1427828 TI - The TCF8 gene encoding a zinc finger protein (Nil-2-a) resides on human chromosome 10p11.2. AB - The TCF8 gene encodes a zinc finger protein (Nil-2-a). Nil-2-a inhibits T lymphocyte-specific interleukin 2 (IL2) gene expression by binding to a negative regulatory domain 100 nucleotides 5' of the IL2 transcription start site. Southern hybridization and somatic cell hybrids are used to demonstrate that the murine and human genomes contain related genes for Nil-2-a. TCF8 resides on human chromosome 10. Fluorescent in situ hybridization is employed to localize TCF8 to 10p11.2. PMID- 1427829 TI - Identification of polymorphic simple sequence repeats in the genome of the zebrafish. AB - The zebrafish has drawn a great deal of attention as a developmental system because it offers the ability to combine excellent embryology and genetics. Here, we report that simple sequence repeats are abundant in the zebrafish genome and are highly polymorphic between two outbred lines, making them useful markers for the construction of a genetic map of this organism. PMID- 1427830 TI - The X-Y homologous gene amelogenin maps to the short arms of both the X and Y chromosomes and is highly conserved in primates. PMID- 1427831 TI - Human DNA polymerase delta gene maps to region 19q13.3-q13.4 by in situ hybridization. PMID- 1427832 TI - Linkage heterogeneity between the C3 and LDLR and the APOA4 and APOA1 loci in baboons. AB - We detected linkage in baboons between loci for the third component of complement (C3) and the low-density lipoprotein receptor (LDLR), lod score = 5.53, and loci for apolipoprotein A1 (APOA1) and apolipoprotein AIV (APOA4), lod score = 14.59. We also found evidence for linkage heterogeneity among the baboon pedigrees between LDLR and C3 (P = 0.04) and between APOA1 and APOA4 (P = 0.01). PMID- 1427833 TI - Organization of the human monoamine oxidase genes and long-range physical mapping around them. AB - A 265-kb yeast artificial chromosome containing sequences for human monoamine oxidase A and B (MAO-A and MAO-B) genes has been characterized. These two genes are localized within a region of about 240 kb and are arranged in a tail-to-tail configuration, with the 3' coding sequences separated by about 50 kb. A region about 2.5 Mb around the MAO loci was mapped by pulsed-field gel electrophoresis (PFGE). Comparisons between the restriction maps derived from the YAC and the long-range map derived from genomic digestions were in general agreement. The important features identified include a CpG island at the 5' end of the MAO-A and MAO-B genes, respectively. The combined information supports the order of markers within this region to be DXS77-DXS7-MAOA-MAOB. PMID- 1427834 TI - Linkage analysis in X-linked congenital stationary night blindness. AB - X-linked congenital stationary night blindness (XL-CSNB) is a nonprogressive disorder of the retina, characterized by night blindness, reduced visual acuity, and myopia. Previous studies have localized the CSNB1 locus to the region between OTC and TIMP on the short arm of the X chromosome. We have carried out linkage studies in three XL-CSNB families that could not be classified as either complete or incomplete CSNB on the criteria suggested by Miyake et al. (1986. Arch. Ophthalmol. 104: 1013-1020). We used markers for the DXS538, DMD, OTC, MAOA, DXS426, and TIMP loci. Two-point analyses show that there is close linkage between CSNB and MAOA (theta max = 0.05, Zmax = 3.39), DXS426 (theta max = 0.06, Zmax = 2.42), and TIMP (theta max = 0.07, Zmax = 2.04). Two multiply informative crossovers are consistent with CSNB lying proximal to MAOA and distal to DXS426, respectively. Multipoint analysis supports this localization, giving the most likely order as DMD-17 cM-MAOA-7.5 cM-CSNB-7.5 cM-DXS426/TIMP-cen, and thus refines the localization of CSNB. PMID- 1427835 TI - Genetic and physical maps of human chromosome 4 based on dinucleotide repeats. AB - Characterization of inherited variations within tandem arrays of dinucleotide repeats has substantially advanced the construction of genetic maps using linkage approaches over the last several years. Using a backbone of 10 newly identified microsatellite repeats on human chromosome 4 and 6 previously identified short tandem repeat element polymorphisms, we have constructed several genetic maps and a physical map of human chromosome 4. The genetic and physical maps are in complete concordance with each other. The genetic maps include a 15-locus microsatellite-based linkage map, a framework map of high support incorporating a total of 39 independent loci, a 25-locus high-heterozygosity, easily used index map, and a gene-based comprehensive map that provides the best genetic location for 35 genes mapped to chromosome 4. The 16 microsatellite markers are each localized to one of nine regions of chromosome 4, delineated by a panel of somatic cell hybrids. These results demonstrate the utility of PCR-based repeat elements for the construction of genetic maps and provide a valuable resource for continued high-resolution mapping of chromosome 4 and of genetic disorders to this chromosome. PMID- 1427836 TI - Chromosomal assignment of a gene encoding a new collagen type (COL15A1) to 9q21 - > q22. AB - The collagens constitute a large family of extracellular matrix components primarily responsible for maintaining the structure and biological integrity of connective tissue. These proteins exhibit considerable diversity size, sequence, tissue distribution, and molecular composition. Fourteen types of homo- and/or heterotrimeric molecules, thus far reported, are encoded by a minimum of 27 genes. Nineteen of these genes, including several that are closely linked, have been assigned to 10 separate autosomes, and one collagen gene has been mapped to the X chromosome. We have isolated a 2.1-kb human cDNA clone coding for a collagen molecule different in sequence and structure from types I-XIV collagens. This polypeptide has been designated the alpha 1 chain of type XV collagen. To determine the location of the corresponding gene, the cDNA clone was hybridized to rodent-human hybrid DNAs and to human metaphase chromosomes. The results obtained using the hybrid cell lines showed that this newly identified collagen gene, COL15A1, is present in the pter --> q34 region of chromosome 9. In situ hybridization allowed sublocalization to 9q21 --> q22, a region to which no other collagen genes had previously been assigned. Our data further demonstrate the complex arrangement of the many collagen genes in the human genome. PMID- 1427837 TI - The mouse alpha 1(XII) and human alpha 1(XII)-like collagen genes are localized on mouse chromosome 9 and human chromosome 6. AB - Type XII collagen is a member of the FACIT (fibril-associated collagens with interrupted triple helices) group of extracellular matrix proteins. Like the other members of this group, collagen types IX and XIV, type XII has alternating triple-helical and non-triple-helical domains. Because of its structure, its association with collagen fibrils, and its distribution in dense connective tissues, type XII is thought possibly to act as a cross-bridge between fibrils and resist shear forces caused by tension. A portion of the ffuse gene was isolated by screening a genomic library with a chicken alpha 1 (XII) cDNA probe, followed by subcloning and sequence analysis. Comparison of exon sequences with the sequence of a mouse cDNA clone allowed the mouse gene to be identified as the alpha 1 (XII) collagen gene. In the mouse, Col12a1 is located on chromosome 9, as determined by linkage analysis using DNA from interspecific backcrosses with Mus spretus. Screening of a human genomic library also allowed the isolation of a human alpha 1(XII)-like gene (CoL12A1). This gene was mapped to chromosome 6 by blot hybridization to DNA from human/hamster hybrid cell lines. This information should prove useful in determining the role of type XII collagen genes as candidate genes in inheritable connective tissue diseases. PMID- 1427838 TI - Physical and genetic mapping of the telomeric major histocompatibility complex region in man and relevance to the primary hemochromatosis gene (HFE). AB - We performed pulsed-field gel electrophoresis (PFGE) on genomic DNA from a radiation hybrid (RH) cell line and constructed a high-resolution physical map of the major histocompatibility complex class I region in 6p21.3, where the gene for primary hemochromatosis (HFE) is believed to be located. Due to the intact microsegment of hemizygous human genomic DNA preserved in the RH cell line, simplified and distinct restriction fragment banding patterns were generated. Using the RH cell line, we were able to extend the physical map of the HLA class I region to about 3000 kb, order the known HLA class I genes from centromere to telomere: HLA-B, -C, -E, (-A, -H, -G), and -F, and orient the HLA-F gene along the chromosome. The proximity of HLA-F to HLA-A was confirmed by linkage and linkage disequilibrium analysis. This study shows that RH cell lines can be useful for constructing long-range physical maps in specific regions of the human genome with PFGE. Physical and genetic mapping studies of this region are consistent with a localization of the HFE gene proximal or distal to HLA-A. PMID- 1427839 TI - Mapping human chromosomes by walking with sequence-tagged sites from end fragments of yeast artificial chromosome inserts. AB - Sequence-tagged sites (STSs) derived from end fragments of chromosome-specific yeast artificial chromosomes (YACs) can facilitate the assembly of an overlapping YAC/STS map. Contigs form rapidly by iteratively screening YAC collections with end-fragment STSs from YACs that have not yet been detected by any previous STS. The map is rendered rapidly useful during its assembly by incorporating supplementary STSs from genes and genetic linkage probes with known locations. Methods for the systematic development and testing of the end-fragments STSs are given here, and a group of 100 STSs is presented for the X chromosome. The mapping strategy is shown to be successful in simulations with portions of the X chromosome already largely mapped into overlapping YACs by other means. PMID- 1427840 TI - Detection of single DNA base mutations with mismatch repair enzymes. AB - A novel method for identifying DNA point mutations has been developed by using mismatch repair enzymes. The high specificity of the Escherichia coli MutY protein has permitted the development of a reliable and sensitive method for the detection and characterization of point mutations in the human genome. The MutY protein is involved in a repair pathway that can convert A/G or A/C mismatches to C/G or G/C basepairs, respectively. A/G or A/C mismatches formed by hybridization between two amplified genomic DNA samples or between specific DNA probes and target DNA are nicked at the mispaired adenine strand by MutY protein. As little as 1% of the mutant sequence can be detected by the mismatch repair enzyme cleavage (MREC) method in a mixture of normal and mutated DNAs (e.g., mutant cells are only present in 1% of the normal cell background). By using different probes, the assay also can determine the nucleotide sequence of the mutation. We have applied this method to detect single-base substitutions in human oncogenes. PMID- 1427841 TI - A random STS strategy for construction of YAC contigs spanning defined chromosomal regions. AB - Sequence tagged sites (STSs) that were generated via Alu-element-mediated polymerase chain reaction (Alu-PCR) and mapped to human Xq26 were used to isolate and overlap yeast artificial chromosomes (YACs). By collating the results of primary pool screening, the order of STSs and YACs was postulated directly. Subsequent isolation of 11 key YACs from 75 positive pools confirmed the proposed contig. Although only a small subset of the available Alu-PCR fragments was used, the STSs were generated at sufficient density to isolate all the YACs required and to identify all except one overlap directly. The results confirmed physical linkage of HPRT to DXS86 and DXS144E. Long-range continuity was determined purely by analysis of the 11 YAC colonies and required no end-rescue. This strategy is therefore an effective approach for the construction of YAC contigs spanning discrete chromosomal regions contained within somatic cell hybrids, with minimal prior knowledge of the region. PMID- 1427842 TI - cDNA surveying of specific tissue expression of human chromosome 19 sequences. AB - cDNA surveying is a straightforward approach for identifying sequences in genomic clones expressed in specific tissues. It has been applied to a subchromosomal region of human chromosome 19 (19q13.2-q13.4), a region that contains several known expressed sequences including the locus for myotonic dystrophy (DM). Genomic clones were selected from this region by probing a human placental cosmid library with a chromosome 19q-specific minisatellite sequence, or human genomic clones were isolated from a cosmid library constructed from a human chromosome 19q13.2-q13.3 hamster hybrid cell line using human repetitive DNA as probe. Pooled cDNAs synthesized from RNA of specific tissues characteristically affected in DM were depleted in repetitive sequences and used as hybridization probes against gridded cosmid arrays. DNA from the cDNA-positive cosmid clones was transferred to nylon filters and reprobed with cDNAs to identify restriction fragments that were expressed in these tissues. Hybridizing restriction fragments were subcloned, sequenced, and demonstrated to be nonrepetitive. Primer pairs complementary to subcloned sequences were constructed and used for PCR amplification of cDNA synthesized from RNA of tissues affected in myotonic dystrophy. PCR products were sequenced to verify the identity of expressed genomic DNA and its corresponding cDNA. PMID- 1427843 TI - Localization of the gene encoding R kappa B (NFRKB), a tissue-specific DNA binding protein, to chromosome 11q24-q25. AB - Although NF (nuclear factor)-kappa B binds in vitro to several of the kappa B regulatory elements found in cellular and viral genes, another DNA binding protein, R kappa B, also binds to a related variant of the kappa B site that regulates interleukin-2 receptor alpha-chain gene expression, a critical event in T cell activation. Southern blot analysis of a human-mouse somatic cell hybrid panel and in situ hybridization using a fluorescent genomic R kappa B probe have allowed assignment of the R kappa B gene (NFRKB) to 11q24-q25. The NFRKB locus is in close proximity to the chromosomal breakpoint implicated in Ewing sarcoma, but it does not appear to span this region. Nonetheless, NFRKB may be particularly useful as the most telomeric marker thus far assigned to 11q. PMID- 1427844 TI - Physical mapping of the albino-deletion complex in the mouse to localize alf/hsdr 1, a locus required for neonatal survival. AB - The albino-deletion complex in the mouse defines a genetically well-characterized region of chromosome 7 in which a number of loci essential for normal development and viability reside. One locus, designated alf or hsdr-1, is necessary for neonatal survival. Its absence results in hypoglycemia associated with biochemical and ultrastructural abnormalities in hepatocytes and proximal tubule cells of the kidney. We constructed a long-range physical map of the region defined by the proximal segment of the albino-deletion complex as a step toward localizing alf/hsdr-1. Sixteen markers, including 11 whose isolation is described here and in the accompanying paper (A. Schedl et al., 1992, Genomics 14, 288 297), were ordered on a panel of albino-deletion DNAs and their distribution was examined by pulsed-field gel electrophoresis. The resulting approximately 4300-kb physical map covers the entire region absent from the prototypic alf/hsdr-1 deletion c14CoS, estimated as approximately 3600 kb. Since the deletion c11DSD complements and overlaps most of c14CoS, alf/hsdr-1 was mapped at the proximal extreme of c14CoS, approximately 3000 kb from the albino locus. The density of CpG islands was found to be very heterogeneous across the region mapped. PMID- 1427845 TI - Chromosome jumping from flanking markers defines the minimal region for alf/hsdr 1 within the albino-deletion complex. AB - The locus alf/hsdr-1, defined by the albino-deletion complex on mouse chromosome 7, is essential for neonatal survival. Animals homozygous for a subset of the deletions die shortly after birth due to impaired gene expression in liver parenchymal cells and kidney proximal tubular cells. Here, we describe a detailed analysis of the region containing alf/hsdr-1 by means of chromosome jumping from flanking markers. Three chromosome jumping libraries based on the restriction enzymes XmaI and SalI were constructed. Isolation of eight jumping clones distributed over 450 kb allowed more than 240 kb to be cloned in genomic lambda and cosmid libraries. Five of the probes map within the minimal genetic interval for alf/hsdr-1, which is defined by the proximal borders of the deletions c10R75M and c11DSD. The breakpoints of these deletions were precisely mapped, which allowed alf/hsdr-1 to be localized to a 310-kb interval. PMID- 1427846 TI - The gene for Aarskog syndrome is located between DXS255 and DXS566 (Xp11.2-Xq13). AB - Aarskog syndrome has been mapped to Xq13 on the basis of a patient carrying an Xq13:8p21.2 translocation. We have identified a new microsatellite marker in a clone mapping to this region (HX60;DXS566). Using primers flanking this microsatellite along with primers detecting a microsatellite at PGK1P1 and DXS255, and DXS72, we have performed a multipoint analysis in a large kindred with Aarskog syndrome. Our results suggest that the Aarskog locus lies proximal to Xq13. This is supported by the recent redefining of the breakpoint of the original translocation as between DXS14 (Xp11.21-p11.1) and DXS146 (Xp11.23 p11.22). PMID- 1427847 TI - Mapping human X-linked genes in the phalangerid marsupial Trichosurus vulpecula. AB - We mapped 15 human X-chromosome markers in the common brush-tailed possum, Trichosurus vulpecula (Kerr), which represents the Australian marsupial family Phalangeridae. In situ hybridization was used to localize highly conserved human X-linked genes to chromosomes of T. vulpecula diploid lines. Ten genes located on the long arm of the human X (human Xq genes) all mapped to the possum X chromosome. However, all five genes located on the short arm of the human X (human Xp genes) mapped to autosomes. These findings confirm our previous work, which showed that the X chromosome in macropodid and dasyurid marsupials bears all the human Xq genes but none of the human Xp genes studied. This suggests that the marsupial X is highly conserved, but its gene content reflects that of only part of the eutherian X, a result consistent with our hypothesis that an autosomal region was added to the X early in eutherian divergence. PMID- 1427849 TI - Characterization of yeast artificial chromosomes from Plasmodium falciparum: construction of a stable, representative library and cloning of telomeric DNA fragments. AB - Molecular genetic studies of the human malaria parasite Plasmodium falciparum have been hampered in part due to difficulties in stably cloning and propagating parasite genomic DNA in bacteria. This is thought to be a result of the unusual A+T bias (>80%) in the parasite's DNA. Pulsed-field gel electrophoretic separation of P. falciparum chromosomes has shown that large chromosomal polymorphisms, resulting from the deletion of DNA from chromosome ends, frequently occur. Understanding the biological implications of this chromosomal polymorphism will require the analysis of large regions of genomic, and in particular telomeric, DNA. To overcome the limitations of cloning parasite DNA in bacteria, we have cloned genomic DNA from the P. falciparum strain FCR3 in yeast as artificial chromosomes. A pYAC4 library with an average insert size of approximately 100 kb was established and found to have a three to fourfold redundancy for single-copy genes. Unlike bacterial hosts, yeast stably maintain and propagate large tracts of parasite DNA. Long-range restriction enzyme mapping of YAC clones demonstrates that the cloned DNA is contiguous and identical to the native parasite genomic DNA. Since the telomeric ends of chromosomes are underrepresented in YAC libraries, we have enriched for these sequences by cloning P. falciparum telomeric DNA fragments (from 40 to 130 kb) as YACs by complementation in yeast. PMID- 1427848 TI - The 5' ends of LINE1 repeats in rabbit DNA define subfamilies and reveal a short sequence conserved between rabbits and humans. AB - The 5' ends of five full-length LINE1 (L1) repeats from the rabbit genome (L1Oc) were mapped and their nucleotide sequences determined. Computer-generated alignments showed that these five L1Oc repeats can be divided into subfamilies, each of which has a characteristic sequence upstream of the first open reading frame (ORF1). These five L1Ocs range in size from 6.5 to 7.3 kb, with 5' ends located 76 to 1125 bp upstream of ORF1. Two of these subfamilies appear to have diverged from a common ancestor at least 66 million years ago. Comparisons of the 5' ends of L1s from rabbit, human, mouse, and rat show no common sequence 5' to ORF1, except for a 22-bp sequence that is found near the beginning of all characterized full-length L1s from rabbit and human. A statistical analysis indicates that this 22-bp aligned block is highly significant. Part of this 22-bp sequence matches the microE1 binding site in immunoglobulin gene enhancers. This strong conservation suggests that the microE1 binding site may be part of a transcriptional regulatory element at the 5' ends of rabbit and human L1 repeats. PMID- 1427850 TI - Comparative anatomy of the primate major histocompatibility complex DR subregion: evidence for combinations of DRB genes conserved across species. AB - The class II region of the human major histocompatibility complex (HLA) is made up of three major subregions designated DR, DQ, and DP. With the aim of gaining an insight into the evolution and stability of DR haplotypes, a total of 63 cosmid clones were isolated from the DR subregion (Gogo-DR) of a western lowland gorilla. All but one of these cosmid clones were found to fall into two clusters. The larger cluster, A, was defined by 41 overlapping cosmid clones and contained a DRB gene segment made up of exons 4 through 6 and four DRB genes, designated Gogo-DRB6, Gogo-DRB5*01, Gogo-DRB8, and Gogo-DRB3*01. The total length of this cluster was approximately 180 kb. The second cluster, B, encompassed a contiguous DNA stretch of approximately 145 kb and was composed of 21 overlapping cosmid clones. Cluster B contained three DRB genes, designated Gogo-DRB1*08, Gogo-DRB2, and Gogo-DRB3*02. One cosmid clone (WP1-9) containing a DRB pseudogene could not be linked to either cluster A or B. Neither the organization of cluster A nor that of cluster B was identical to that of known HLA-DR haplotypes. However, two gorilla DRB genes, Gogo-DRB6 and Gogo-DRB5*01, the human counterparts of which are linked in the HLA-DR2 haplotype, were found to be located next to each other in cluster A. The arrangement of the Gogo-DRB genes in cluster B, which is presumed to be the gorilla DR8 haplotype, was similar to that of HLA-DR3/DR5/DR6 haplotypes and to that of the presumed ancestral HLA-DR8 haplotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427851 TI - The telomeric 60 kb of chromosome arm 4p is homologous to telomeric regions on 13p, 15p, 21p, and 22p. AB - A telomere YAC clone containing the most distal 115 kb of chromosome arm 4p has been previously isolated. This clone is of particular interest as it spans a potential candidate region for the Huntington disease gene. The YAC was subcloned into a phage vector, and a high-resolution restriction map extending to within 13 kb of the telomere was constructed. In situ hybridization of the YAC to human metaphase spreads gives a peak of hybridization on 4pter but also an increase in the number of signals close to several other telomeres. Where possible, these results were investigated further by the hybridization of probes from the YAC to somatic cell hybrids containing single human chromosomes. This analysis indicates that the most telomeric 60 kb of chromosome arm 4p is homologous to telomeric regions on 13p, 15p, 21p, and 22p. The extent of this homology makes it less likely that the mutation for Huntington's disease is located within the telomere YAC clone. PMID- 1427852 TI - Pig standard bivariate flow karyotype and peak assignment for chromosomes X, Y, 3, and 7. AB - A standard pig flow karyotype (2N = 38 chromosomes) was defined by standardization of several flow karyotypes obtained from stimulated peripheral blood lymphocytes of normal male and female pigs. Depending on the animals under study, the flow analysis of their chromosome suspensions gave rise to bivariate flow karyotypes comprising from 15 to 17 peaks, of which 11 to 15 represented single chromosomes. The results were used to propose a peak nomenclature. In addition, a male miniature pig lymphoblastoid cell line was characterized by flow cytogenetics. A very high-resolution flow karyotype, in which all peaks but one superimposed on those of the standard karyotype, was obtained. Peaks were assigned for chromosomes X and Y. Analysis of flow karyotypes obtained from translocated t(3,7)(p1.3;q2.1) pigs combined with polymerase chain reaction (PCR) studies of major histocompatibility complex (MHC)-linked sequences on flow-sorted chromosomes allowed identification of peaks 3 and 7 of normal pig chromosomes and of the derivative chromosomes associated with the t(3,7)(p1.3;q2.1) translocation. PMID- 1427853 TI - The defensin-related murine CRS1C gene: expression in Paneth cells and linkage to Defcr, the cryptdin locus. AB - The site of defensin-related CRS1C gene expression in mouse small bowel and the chromosomal location of the CRS1C locus, Defcr-rs1, have been determined. CRS1C (cryptdin-related sequence 1C) mRNA is an abundant small intestinal sequence that exhibits extensive similarity to the prepro-coding regions of defensin mRNAs yet does not encode a defensin (A. J. Ouellette and J. C. Lualdi, 1990, J. Biol. Chem. 265: 9831-9837). Using sequence-specific probes, CRS1C mRNA was detected in Paneth cells at the base of intestinal crypts by in situ hybridization. Southern blot analysis of genomic DNAs from inbred and recombinant inbred (RI) mouse strains, also conducted with probes specific for CRS1C, showed that the CRS1C locus maps to the proximal region of Chromosome 8. In 62 RI strains, no discordancies were found between Defcr-rs1 and Defcr, the cryptdin gene. Thus, both the Defcr-rs1 and the Defcr genes are expressed in Paneth cells and both are genetically inseparable within 1.58 cM on Chromosome 8. These studies identify a second defensin-related Paneth cell gene in mice. PMID- 1427854 TI - Identification of three new genes and estimation of the size of the carcinoembryonic antigen family. AB - Using carcinoembryonic antigen (CEA) subgroup-specific degenerate PCR primers, we have identified three new CEA gene family member L/N exons (CGM9, CGM10, and CGM11) and all previously reported L/N exons of the CEA subgroup (CEA, BGP, NCA, CGM1, CGM2, CGM6, CGM7, and CGM8). This suggests that the CEA subgroup contains 11 genes. CGM9, CGM10, and CGM11 seem to be pseudogenes. A deletion of an asparagine in CGM9 results in loss of a glycosylation site, which is conserved throughout the CEA gene family. We have previously suggested the number of genes in the pregnancy-specific glycoprotein (PSG) subgroup to be 11, which together with this study indicates that the CEA gene family contains 22 genes in all. Parsimony analysis of the CEA subgroup interrelationships suggests that CGM7 occupies the most primitive position within the CEA subgroup, being a sister group to the rest. CEA, BGP, NCA, and CGM1 form a fairly well-supported group within the CEA subgroup. PMID- 1427855 TI - Detection of a polymorphism within the pepsinogen C gene with PCR: construction of a linkage map around PGC from 6p11-6p21.3. AB - An insertion/deletion polymorphism between exons 7 and 8 of the pepsinogen C gene (PGC), previously detectable with Southern analysis, was formatted for detection with PCR. Alleles were rapidly typed by UV irradiation of ethidium bromide stained agarose gels. Whereas Southern analysis revealed two alleles, the smaller fragments generated with PCR allowed the resolution of three alleles that were previously scored as a single allele and increased the heterozygosity of the system from 0.20 to 0.53. After a set of reference families was genotyped with the PCR-based polymorphism, a linkage map around the PGC gene on chromosome 6 was constructed. This included the HLA cluster and the highly informative D6S223 locus. PGC lies 22 cM proximal to HLA-DPB and between D6S5 and D6S4 at distances of 4.5 and 13.1 cM, respectively. PMID- 1427857 TI - Detailed mapping around the breakpoint of (3;8) translocation in familial renal cell carcinoma and FRA3B. AB - As a critical step toward cloning the breakpoint of the (3;8) translocation observed in familial renal cell carcinoma and a common fragile site on chromosome 3p (FRA3B), we have characterized the 3p14 region containing the breakpoint and FRA3B by fluorescence in situ hybridization (FISH), pulsed-field gel electrophoresis (PFGE), and genetic linkage analysis. Of 23 cosmids mapped by FISH, 14 cosmids were distal to the breakpoint of t(3;8) and 9 were proximal. Analyses of FRA3B by FISH were identical to those for the (3;8) breakpoint and indicated that the breakpoint of t(3;8) occurred at or very close to the fragile site. We have also constructed a genetic linkage map and a preliminary long-range restriction map using PFGE of the 3p14 region. The linkage results were consistent with the physical data. The combined results of FISH, PFGE, and linkage analysis establish a basis for further experiments to clone the (3;8) breakpoint and FRA3B. PMID- 1427856 TI - Feline arylsulfatase B (ARSB): isolation and expression of the cDNA, comparison with human ARSB, and gene localization to feline chromosome A1. AB - Arylsulfatase B (ARSB) is the lysosomal enzyme that catalyzes the hydrolysis of 4 sulfate groups from N-acetylgalactosamine 4-sulfate moieties on the glycosaminoglycans, dermatan sulfate and chondroitin sulfate A. In man, a deficiency of this enzymatic activity causes the lysosomal storage disorder, Maroteaux-Lamy disease (mucopolysaccharidosis Type VI; MPS VI). MPS VI in Siamese cats also has been described, and the comparative pathologic and biochemical abnormalities of the human and feline disorders have been well characterized. The present study describes the isolation and expression of cDNAs encoding feline ARSB and the assignment of the feline ARSB gene to feline chromosome A1. The full length feline ARSB cDNA sequence is 1939 bp, including 3 and 328 bp of 5' and 3' untranslated sequences, respectively, and a 1608-bp open reading frame encoding 535 amino acids. The predicted human and feline ARSB proteins are 91% identical and 94% similar. However, despite this high homology, the predicted feline ARSB polypeptide has nine cysteine residues, while the human enzyme has eight. The presence of the extra cysteine residue at position 451 in the feline enzyme may explain why feline ARSB is a homodimer and the human enzyme is a monomer. To facilitate comparative structure/function studies of the human and feline enzymes and to initiate somatic gene therapy trials in the MPS VI cats, a full-length feline ARSB cDNA was reconstructed from a 1440-bp partial cDNA and an ARSB fragment amplified from feline first-strand cDNA by the polymerase chain reaction. The functional integrity of this cDNA was demonstrated by transient expression in human embryonic kidney cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427858 TI - A somatic cell hybrid panel for regional mapping of human chromosome 18. AB - We have produced and characterized a panel of seven somatic cell hybrids defining eight potential intervals on human chromosome 18. Using 24 markers that have previously been assigned to this chromosome, we have placed markers into six of these regions. The gene for alpha 2-plasmin inhibitor (PLI) and the anonymous DNA segment locus D18S23 are excluded from this chromosome. PMID- 1427859 TI - Length and sequence variation in the apolipoprotein B intron 20 Alu repeat. AB - We have developed a single-stranded conformation polymorphism (SSCP) protocol for typing both sequence and length variations in an Alu element located in intron 20 of the human apolipoprotein B (apo B) gene. Using the polymerase chain reaction (PCR), we simultaneously amplified and isotopically labeled the apo B intron 20 Alu. The Alu tail, which is composed of two arrays of variable numbers of tandem repeats, (TTTX)y (X = A or G) and (T)z, was separated from the rest of the PCR product by restriction enzyme digestion with PstI. Length variation in the Alu tail (IN20-REP) was thus separated from sequence variation in the Alu body (IN20 SEQ), rendering the SSCP patterns both eaiser to interpret and more informative. In a sample of 242 unrelated individuals from Nancy, France, we observed 11 SSCP alleles at the IN20-SEQ locus that differed only in sequence. At the IN20-REP locus, we observed 7 alleles that differed in both sequence and length. All alleles at both loci were subcloned and sequenced. One additional allele that did not undergo a detectable mobility shift in SSCP gels was uncovered at each locus during sequencing of the SSCP alleles. The additional IN20-SEQ allele was typed by restriction enzyme digestion. Although the number of IN20-SEQ and IN20-REP alleles was large, most were uncommon; the three most common alleles at each locus represented more than 94% of those sampled. We also typed the children of the 242 unrelated French individuals, enabling verification of the Mendelian segregation of the two loci and construction of haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427860 TI - The human Pi class glutathione transferase sequence at 12q13-q14 is a reverse transcribed pseudogene. AB - A previous in situ hybridization study with a Pi class glutathione S-transferase cDNA probe revealed the presence of hybridizing sequences on the long arms of chromosomes 11 and 12. Since the GSTP1 gene is known to be on chromosome 11 and since it is thought that chromosomes 11 and 12 arose from an ancient tetraploidization event, it was of interest to determine if the gene on chromosome 12 encoded a closely related Pi class glutathione S-transferase isoenzyme. This gene has now been cloned and sequenced. The results are surprising and indicate that the gene is a partial reverse-transcribed pseudogene that has been inserted into the genome at 12q by chance and has not resulted from the prior tetraploidization of the human genome. PMID- 1427861 TI - The human galactose-1-phosphate uridyltransferase gene. AB - Classical galactosemia is an inborn error of metabolism caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT). Standard treatment with dietary galactose restriction will reverse the potentially lethal symptoms of the disease that are manifest in the newborn period. However, the long-term prognosis for these patients is variable. As a first step toward investigating the molecular basis for phenotypic variation in galactosemia, we have cloned and sequenced the entire gene for human galactose-1-phosphate uridyltransferase. This gene is organized into 11 exons spanning 4 kb. In exons 6, 9, and a portion of 10, there is a high degree of amino acid sequence conservation among Escherichia coli, yeast, mouse, and human. We have identified a number of nucleotide changes in the GALT genes of galactosemic patients that alter conserved amino acids. The most common of these is an A to G transition at nucleotide position 1470, converting a glutamine to an arginine at amino acid codon position 188 (Q188R).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427862 TI - Construction and characterization of a yeast artificial chromosome library containing 1.5 equivalents of human chromosome 21. AB - A library of yeast artificial chromosomes (YACs) was constructed from a human/hamster somatic cell hybrid containing human chromosome 21 (q11-qter). Cells were embedded in agarose, and the DNA was partially digested with EcoRI, released into solution by agarase treatment of the agarose plugs, ligated into pYAC4, and transferred into yeast. Double screening of the yeast transformants with human and hamster genomic DNA allowed the selection of clones hybridizing only with human DNA. The library consists of 321 clones, amounting to 1.5 equivalents (61 Mb) of chromosome 21. The mean YAC size calculated from 178 clones is 190 +/- 100 kb. Screening of the library with eight sequence-tagged sites gave six positives. Among 21 YACs tested by in situ hybridization, 17 mapped to chromosome 21. PMID- 1427864 TI - The gene for the cell adhesion molecule M-cadherin maps to mouse chromosome 8 and human chromosome 16q24.1-qter and is near the E-cadherin (uvomorulin) locus in both species. AB - A mouse myotube-derived cDNA encoding the Ca(2+)-dependent cell adhesion molecule M-cadherin was used to study the segregation of the corresponding gene Cdh3 in a mouse interspecific backcross. Cdh3 was found to be unlinked to the N-cadherin gene but linked to the E-cadherin (uvomorulin) locus on chromosome 8 in a region of conserved synteny with human chromosome 16q. The gene order cen-Junb-Um-Tat (Cdh3/Aprt) was determined. The human homologue CDH3 was mapped to chromosome 16q24.1-qter by analyzing human/mouse somatic cell hybrids. PMID- 1427863 TI - Determination of the nucleotide sequence and chromosomal localization of the ATP2B2 gene encoding human Ca(2+)-pumping ATPase isoform PMCA2. AB - The plasma membrane Ca(2+)-pumping ATPase (Ca(2+)-ATPase) is responsible for maintaining calcium homeostasis in eukaryotic cells. The Ca(2+)-ATPase is a family of pumps that are encoded by at least four genes. A cDNA for the human version of Ca(2+)-ATPase isoform PMCA2 was isolated and characterized. Comparison of the human and rat cDNA sequences showed that they were 95% homologous in the coding domain, and this homology was reflected in the deduced protein sequence where greater than 98% homology between the human and rat sequences was found. The amino acid differences that were found were almost all conservative. The PMCA2 cDNA was used to probe Southern blots of human-rodent somatic cell hybrid DNAs; the results indicated that the human PMCA2 gene was located on chromosome 3. PMID- 1427865 TI - Neural retina-specific leucine zipper gene NRL (D14S46E) maps to human chromosome 14q11.1-q11.2. AB - The product of a neural retina-specific gene, NRL, belongs to the "leucine zipper" family of DNA-binding proteins and has a strong similarity to the v-maf oncogene product. The NRL gene maps to human chromosome 14 by Southern blot analysis of genomic DNA from a human-rodent somatic cell hybrid panel. In situ hybridization to metaphase chromosomes has further sublocalized the gene to the region 14q11.1-q11.2. D14S46E has now been assigned to the NRL gene. Because of its specific pattern of expression, NRL is a candidate gene for retinal diseases. PMID- 1427866 TI - Sequence-tagged sites (STSs) for a set of mapped markers on chromosome 21. AB - Sequence tagged sites (STSs) have been proposed as a "common language" for comparing physical and genetic maps of the human genome produced by a variety of techniques. We have produced 44 STSs from 38 mapped loci on human chromosome 21. The STSs represent most of the loci designated as genetic reference or ordered physical framework markers, along with a number of others chosen to span all regions of 21q. Of the STSs, 12 are from gene segments, including 4 from exons of the APP gene encoding the amyloid beta protein precursor, and 32 mark anonymous DNA loci. These STSs make each of the corresponding loci readily accessible to the research community without the need for exchange of clones. These sites also represent multiple start points for the isolation of YAC clones that should permit overlapping the entire chromosome 21 long arm as cloned DNA. PMID- 1427867 TI - Genetic mapping of the integrin alpha 1 gene (Vla1) to mouse chromosome 13. AB - The integrin alpha 1 chain (Vla1) associates with the beta 1 chain to form a heterodimer that functions as a dual laminin/collagen receptor in neural cells and hematopoietic cells. We have used an interspecies backcross gene-mapping technique to map the Vla1 gene to the distal end of chromosome 13 in the mouse genome. The Vla1 locus is located 3.5 cM distal to Ctla-3 and 7.8 cM distal to Htrla. We have further characterized this locus in recombinant inbred (RI) mice by examining the strain distribution patterns of nine genomic DNA restriction fragment length variants detected with alpha 1 cDNA probes. The RI gene mapping did not show linkage to previously mapped genes or mutants in the AXB, BXA, or AKXD RI sets and therefore defines a new genetic marker for the distal end of chromosome 13 in these RI sets. PMID- 1427868 TI - Linkage mapping of the AML1 gene on human chromosome 21 using a DNA polymorphism in the 3' untranslated region. AB - We have detected a polymorphism in the 3' untranslated region of the AML1 gene, which is located at the breakpoint on chromosome 21 in the t(8;21)(q22;q22.3) translocation often associated with patients with acute myeloid leukemia. Informative CEPH families were genotyped for this polymorphism and used to localize the gene on the linkage map of human chromosome 21. The AML1 gene is located between the markers D21S216 and D21S211, in chromosomal band 21q22.3. PMID- 1427869 TI - The gene for X-linked hydrocephalus maps to Xq28, distal to DXS52. AB - We report the study of five independent X-linked hydrocephalus (HSAS1) families with polymorphic DNA markers of the Xq28 region. A total of 58 individuals, including 7 living affected males and 22 obligate carriers, have been studied. Maximum lod score was 7.21 at theta = 2.40% for DXS52 (St14-1). A single recombination event was observed between this marker and the HSAS1 locus. Other markers studied were DXS296 (Z = 2.02 at theta = 2.5%), DXS304 (Z = 4.37 at theta = 7.8%), DXS74 (Z = 3.50 at theta = 0%), DXS15 (Z = 1.96 at theta = 5.7%), DXS134 (Z = 3.31 at theta = 0%), and F8C (Z = 5.79 at theta = 0%). These data confirm the localization of the HSAS1 gene to Xq28 and provide evidence for genetic homogeneity of this syndrome. In addition, examination of two obligate recombinant meioses along with multipoint linkage analysis supports the distal localization of the HSAS1 locus with respect to the DXS52 cluster. These observations are of potential interest for future studies aimed at HSAS1 gene characterization. PMID- 1427871 TI - Chromlook: an interactive program for error detection and mapping in reference linkage data. AB - Preliminary genetic linkage maps of every human chromosome have been generated over the past few years, and efforts to extend and refine these maps are under way. However, fine-resolution mapping is tedious and difficult because the inevitable errors in the data confound estimates of both the placement of loci and the distances between them. Fortunately, in most cases these errors result in observed recombinants where no true recombinant has occurred. The simple strategy presented here identifies these recombinants by relying on the assumption that recombinants between two adjacent markers are relatively rare events. This strategy has been implemented in the computer program CHROMLOOK, and examples of its use are given. Identification of recombinants allows for the directed regenotyping of suspicious data, the quick mapping of new polymorphisms using recombination minimization, and the development of a meiotic breakpoint map. PMID- 1427870 TI - Discrimination between alpha-satellite DNA sequences from chromosomes 21 and 13 by using polymerase chain reaction. AB - alpha-Satellite subfamilies from chromosomes 21 and 13 are almost identical in sequence and cannot be distinguished from each other by hybridization techniques. A general method based on membrane-bound PCR is described here, allowing the discrimination of alpha-satellite DNA sequences from each of these two chromosomes, after detection by Southern blot hybridization. The PCR conditions were developed using somatic hybrid DNAs. The method was tested in membrane-bound PCR by using the alpha-satellite bands from a Southern blot of a CEPH family. The chromosomal origin of these bands, previously determined by linkage analysis, was confirmed by this method. PMID- 1427872 TI - Mapping around the Xq13.1 breakpoints of two X/A translocations in hypohidrotic ectodermal dysplasia (EDA) female patients. AB - Cellular hybrids were obtained from a t(X;12) identified in a female patient with hypohidrotic ectodermal dysplasia (EDA). This rearrangement had the same Xq13.1 cytogenetic breakpoint as a t(X;9) found in a previously observed EDA patient. A comparative analysis of these two rearrangements with nine probes was performed at the molecular level. These probes could define three subregions: three are proximal, two are distal, and four are between the two breakpoints. These last probes should prove useful for cloning the gene. PMID- 1427873 TI - Mapping of bovine markers CYP21, PRL, and BOLA DRBP1 by genetic linkage analysis in reference pedigrees. AB - We have analyzed DNA from 13 bovine reference pedigrees using primers specific for microsatellite markers derived from the 21-steroid hydroxylase (CYP21) and prolactin (PRL) genes and the leukocyte antigen (BOLA DRBP1) pseudogene. Linkage was demonstrated between PRL and BOLA DRBP1 (theta = 0.05; Z = 19.6), cyp21 and PRL (theta = 0.13; Z = 6.8), and BOLA DRBP1 and CYP21 (theta = 0.17; Z = 10.4). These results suggest an order BOLA DRBP1-PRL-CYP21, although in a multilocus analysis the alternative order PRL-BOLA DRBP1-CYP21 was also possible. The data confirm and extend the previously established syntenic relationship between these markers on bovine chromosome 23 and provide points of anchorage for further linkage studies in the reference pedigrees described. PMID- 1427874 TI - Chromosomal localization of the genes encoding the p50/p105 subunits of NF-kappa B (NFKB2) and the I kappa B/MAD-3 (NFKBI) inhibitor of NF-kappa B to 4q24 and 14q13, respectively. AB - The regulation of expression of a variety of genes involved in immune function, inflammation, and cellular growth control, as well as control of expression of certain viruses such as the human immunodeficiency virus (HIV), is dependent on the transcription factor NF-kappa B. In many cells, NF-kappa B is found in the cytoplasm where it is associated with an inhibitor protein known as I kappa B. Recently the genes encoding the p50 and p65 subunits of NF-kappa B, as well as one form of I kappa B/MAD-3 (NFKBI), have been cloned. As part of our goal to determine the chromosomal organization of members of the REL/NFKB family, as well as their inhibitors, we localized the NFKBp50/p105 (NFKB2) and I kappa B/MAD-3 (NFKBI) genes to human chromosome bands 4q24 and 14q13, respectively. PMID- 1427875 TI - Physical localization of chromosome 20 markers using somatic cell hybrid cell lines and fluorescence in situ hybridization. AB - A panel of somatic cell hybrid cell lines containing different parts of human chromosome 20 and fluorescence in situ hybridization have been used to physically localize markers to human chromosome 20. Through these complementary approaches and genetic linkage analysis, D20S16, which is closely linked to the maturity onset diabetes of the young (MODY) locus, was mapped to band 20q12 --> q13.1. The gene for growth hormone-releasing factor (GHRF) was physically mapped and reassigned to 20q11, suggesting that GHRF plays no direct role in MODY. In addition, the genes for the chromosome 20-linked glycogen phosphorylase (GYPB) and the bone morphogenetic protein (BMP2A) have been assigned to chromosome 20p, and the interleukin-6-dependent DNA-binding protein (TCF5) has been assigned to 20q12 --> q13 by hybridization to genomic DNA from the panel of somatic cell hybrid cell lines. These approaches are useful for rapid localization of candidate genes for MODY and other DNA markers mapped to chromosome 20. PMID- 1427876 TI - Detection and characterization of "chimeric" yeast artificial chromosome clones by fluorescent in situ suppression hybridization. AB - "Chimeric" yeast artificial chromosomes (YACs) are clones containing two or more noncontiguous segments of DNA and represent the most common artifact found in total genomic YAC libraries currently used for large-scale genome mapping. These YACs create spurious mapping information that complicates the construction of YAC contigs and leads to erroneous maps during chromosome walks. The presence of these artifactual clones necessitates laborious and time-consuming characterization of each isolated YAC clone, either by comparison of the physical map of the YAC with the corresponding source genomic DNA, or by demonstrating discrepant chromosomal origins for the two ends of the YAC by hybridization or polymerase chain reaction (PCR). Here, we describe a rapid and sensitive method for the assessment of YAC colinearity by fluorescence in situ suppression hybridization (FISSH) by utilizing fluorescein-12-dUTP for labeling YAC clones. We have analyzed 51 YACs and found that 43% (22 out of 51) are chimeric and significantly larger (302 kb) than colinear ones (228 kb). One of the 51 YAC clones (2%) examined contains portions of three chromosomes and 2 (4%) seem to map to a chromosome different than that of the identifying STS. FISSH analysis offers a straightforward visualization of the entire YAC insert on the chromosomes and can be used to examine many YACs simultaneously in few days. PMID- 1427877 TI - Mapping of 50 cosmid clones isolated from a flow-sorted human X chromosome library by fluorescence in situ hybridization. AB - Fifty cosmids have been mapped to metaphase chromosomes by fluorescence in situ hybridization under conditions that suppress signals from repetitive DNA sequences. The cosmid clones were isolated from a flow-sorted human X chromosome library. Thirty-eight of the clones were localized to chromosome X and 12 to autosomes such as chromosomes 3, 7, 8, 14, and 17. Although most of the cosmids mapped to the X chromosome appeared to be scattered along both the short and long arms, 10 cosmids were localized to the centromeric region of the chromosome. Southern blot analysis revealed that only two of these clones hybridized to probe pXBR-1, which detects the DXZ1 locus. In addition, 4 out of 5 cosmids mapped on chromosome 8 also localized on the centromeric region. While localization of X specific cosmids will facilitate the physical mapping of the human X chromosome, cosmids mapped to the centromeric regions of chromosomes X and 8 should be especially useful for studying the structure and organization of these regions. PMID- 1427878 TI - Assignment, by in situ hybridization, of the growth arrest-specific gene, Gas-1, to mouse chromosome 13, bands B3-C2. PMID- 1427879 TI - The gene encoding human plasma carboxypeptidase B (CPB2) resides on chromosome 13. PMID- 1427880 TI - Assignment of the human gene propionyl coenzyme A carboxylase, alpha-chain, (PCCA) to chromosome 13q32 by in situ hybridization. PMID- 1427881 TI - Mapping of the X-linked form of hyper-IgM syndrome (HIGM1) to Xq26 by close linkage to HPRT. PMID- 1427882 TI - Three novel mutations of the ornithine aminotransferase (OAT) gene in gyrate atrophy. PMID- 1427883 TI - DXS89 (pTAK10) detects a homologous sequence on the Y chromosome. PMID- 1427884 TI - Fine mapping and cloning of the breakpoint associated with Menkes syndrome in a female patient. AB - The gene responsible for Menkes syndrome has been assigned to Xq13 by a combination of comparative mapping and linkage analysis. A previous report has mapped the translocation breakpoint associated with the disease in a female patient to an interval delimited by PGK1 and a group of six more proximal Xq13 markers, including DXS56. We have characterized a number of PGK1- or DXS56 positive YACs, from which we have generated six new markers. One of them identifies a small overlap region between a PGK1-positive YAC and three DXS56 positive YACs, distal to the Menkes breakpoint. A 560-kb region covered by a DXS56-positive YAC has been restriction-mapped and subcloned, disclosing a 187-kb MluI fragment astride the breakpoint. A probe mapping distal to the rearrangement in the same interval reveals altered PGFE fragments in a hybrid constructed from the translocation patient's DNA. We describe the development of a cosmid contig extending 150 kb from a nearby CpG island across the breakpoint. This contig includes four adjacent clones displaying cross-specific hybridization. PMID- 1427885 TI - Evidence for the localization of a malignant hyperthermia susceptibility locus (MHS2) to human chromosome 17q. AB - Malignant hyperthermia susceptibility is a lethal autosomal dominant disorder of skeletal muscle metabolism that is triggered by all potent inhalation anesthetic gases. Recent linkage studies suggest a genetic locus for this disorder on 19q13.1. We have previously reported three unrelated families diagnosed with MHS that are unlinked to markers surrounding this locus on 19q13.1. In this report we extend these observations and present linkage studies on 16 MHS families. Four families (25%) were found linked to the region 19q12-q13.2 (Zmax = 2.96 with the ryanodine receptor at theta = 0.0). Five families (31%) were found closely linked to the anonymous marker NME1 (previously designated NM23) on chromosome 17q11.2 q24 (Zmax = 3.26 at theta = 0.0). Two families (13%) were clearly unlinked to either of these chromosomal regions. In five additional families, data were insufficient to determine their linkage status (they were potentially linked to two or more sites). The results of our heterogeneity analyses are consistent with the hypothesis that MHS can be caused in humans by any one of at least three distinct genetic loci. Furthermore, we provide preliminary linkage data suggesting the localization of a gene in human MHS to 17q11.2-q24 (MHS2), with a gene frequency of this putative locus approximately equal to that of the MHS1 locus on 19q. PMID- 1427886 TI - A radiation hybrid map of the region on human chromosome 22 containing the neurofibromatosis type 2 locus. AB - We describe a high-resolution radiation hybrid map of the region on human chromosome 22 containing the neurofibromatosis type 2 (NF2) gene. Eighty-five hamster-human somatic cell hybrids generated by X-irradiation and cell fusion were used to generate the radiation hybrid map. The presence or absence of 18 human chromosome 22-specific markers was determined in each hybrid by using Southern blot hybridization. Sixteen of the 18 markers were distinguishable by X ray breakage in the radiation hybrids. Analysis of these data using two different mathematical models and two different statistical methods resulted in a single framework map consisting of 8 markers ordered with odds greater than 1000:1. The remaining nonframework markers were all localized to regions consisting of two adjoining intervals on the framework map with odds greater than 1000:1. Based on the RH map, the NF2 region of chromosome 22, defined by the flanking markers D22S1 and D22S28, is estimated to span a physical distance of approximately 6 Mb and is the most likely location for 9 of the 18 markers studied: D22S33, D22S41, D22S42, D22S46, D22S56, LIF, D22S37, D22S44, and D22S15. PMID- 1427887 TI - Evidence for a third transcript from the human factor VIII gene. AB - Intron 22 of the human factor VIII gene was recently found to contain a gene, associated with a CpG island, which is transcribed in the direction opposite to factor VIII. We now report that another transcript emanates from the island and is transcribed in the same direction as factor VIII. The divergent transcripts originate within 122 bases of each other. The newly identified 5' exon in intron 22 potentially codes for eight amino acids and is spliced to exons 23-26, with the factor VIII reading frame maintained. The protein encoded by this transcript would include the factor VIII C2 domain, responsible for phospholipid binding and essential for coagulant activity. PMID- 1427888 TI - Systematic detection of errors in genetic linkage data. AB - Construction of dense genetic linkage maps is hampered, in practice, by the occurrence of laboratory typing errors. Even relatively low error rates cause substantial map expansion and interfere with the determination of correct genetic order. Here, we describe a systematic method for overcoming these difficulties, based on incorporating the possibility of error into the usual likelihood model for linkage analysis. Using this approach, it is possible to construct genetic maps allowing for error and to identify the typings most likely to be in error. The method has been implemented for F2 intercrosses between two inbred strains, a situation relevant to the construction of genetic maps in experimental organisms. Tests involving both simulated and real data are presented, showing that the method detects the vast majority of errors. PMID- 1427889 TI - Construction of a yeast artificial chromosome contig encompassing the human alpha 5(IV) collagen gene (COL4A5). AB - A PCR-based screening approach was used to isolate six yeast artificial chromosome (YAC) clones containing segments of the human alpha 5(IV) collagen gene (COL4A5). This gene is located at Xq22 and is known to be involved in the kidney disorder known as Alport syndrome (AS). By analyzing sequence-tagged sites, cDNA content, and rare-cutting restriction site patterns in these YAC clones, a contig that spans the entirety of the alpha 5(IV) gene was constructed. This contig may contain as much as 690 kb of DNA from the alpha 5(IV) locus. On the basis of the information obtained from these YAC clones, the genomic map and gene structure of the alpha 5(IV) gene have been refined. This study has also provided a valuable resource for subsequent studies of the alpha 5(IV) gene and its flanking DNA sequences. PMID- 1427890 TI - Duplication/deficiency mapping of situs inversus viscerum (iv), a gene that determines left-right asymmetry in the mouse. AB - A recessive mutation in the mouse, situs inversus viscerum (iv), results in randomization of organ position along the left-right body axis: approximately 50% of the progeny of homozygous matings exhibit situs solitus and 50% exhibit situs inversus. Recent studies have established genetic linkage between iv and the immunoglobulin heavy chain gene complex (Igh-C), located on distal mouse chromosome 12. In the present study, we have refined the genetic map location of iv relative to the breakpoint of a reciprocal translocation, T(5;12)31H, involving the telomeric region of chromosome 12 distal to Igh-C and the proximal region of chromosome 5. The translocation results in a large 12(5) derivative chromosome and a small 5(12) derivative chromosome. Because mice with either monosomy or tertiary trisomy for the 5(12) chromosomal region are viable, duplication/deficiency mapping is possible. Deficiency mapping was performed by mating iv/iv homozygotes and T31H heterozygotes. Two animals monosomic for distal mouse chromosome 12 were produced. One of the animals with cytogenetically confirmed monosomy for distal chromosome 12 exhibited situs inversus, indicating that the iv mutation is located at or distal to the T31H breakpoint. For duplication analysis, matings were initially carried out between iv/iv homozygotes and unbalanced T31H animals trisomic for distal chromosome 12. Cytogenetically verified tertiary trisomic progeny were identified and backcrossed with iv/iv homozygotes. The resulting trisomic progeny, 50% of which are expected to carry the iv mutation on both cytogenetically normal copies of chromosome 12, were scored for phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427891 TI - Isolation of DNA markers from a region between incontinentia pigmenti 1 (IP1) X chromosomal translocation breakpoints by a comparative PCR analysis of a radiation hybrid subclone mapping panel. AB - A strategy based on the use of human-specific interspersed repetitive sequence (IRS)-PCR amplification was used to isolate regional DNA markers in the vicinity of the incontinentia pigmenti 1 (IP1) locus. A radiation hybrid (RH) resulting from a fusion of an irradiated X-only somatic cell hybrid (C12D) and a thymidine kinase deficient (TK-) hamster cell line (a23) was identified as containing multiple X chromosome fragments, including DNA markers spanning IP1 X-chromosomal translocation breakpoints within region Xp11.21. From this RH, a panel of subclones was constructed and analyzed by IRS-PCR amplification to (a) identify subclones containing a reduced number of X chromosome fragments spanning the IP1 breakpoints and (b) construct a mapping panel to assist in identifying regional DNA markers in the vicinity of the IP1 locus. By using this strategy, we have isolated three different IRS-PCR amplification products that map to a region between IP1 X chromosome translocation breakpoints. A total of nine DNA sequences have now been mapped to this region; using these DNA markers for PFGE analyses, we obtained a probe order DXS14-DXS422-MTHFDL1-DXS705. These DNA markers provide a starting point for identifying overlapping genomic sequences spanning the IP1 translocation breakpoints; the availability of IP1 translocation breakpoints should assist the molecular analysis of this locus. PMID- 1427892 TI - A radiation hybrid map of the proximal short arm of the human X chromosome spanning incontinentia pigmenti 1 (IP1) translocation breakpoints. AB - Radiation hybrid mapping was used in combination with physical mapping techniques to order and estimate distances between 14 loci in the proximal region of the short arm of the human X chromosome. A panel of radiation hybrids containing human X-chromosomal fragments was generated from a Chinese hamster-human cell hybrid containing an X chromosome as its only human DNA. Sixty-seven radiation hybrids were screened by Southern hybridization with sets of probes that mapped to the region Xp11.4-Xcen to generate a radiation hybrid map of the area. A physical map of 14 loci was constructed based on the segregation of the loci in the hybrid clones. Using pulsed-field gel electrophoresis (PFGE) analyses and a somatic cell hybrid mapping panel containing naturally occurring X; autosome translocations, the order of the 14 loci was verified and the loci nearest to the X-chromosomal translocation breakpoints associated with the disease incontinentia pigmenti 1 (IP1) were identified. The radiation hybrid panel will be useful as a mapping resource for determining the location, order, and distances between other genes and polymorphic loci in this region as well as for generating additional region-specific DNA markers. PMID- 1427893 TI - Molecular cloning and characterization of the rat liver IL-6 signal transducing molecule, gp130. AB - Interleukin-6 (IL-6) is a multifunctional cytokine that exerts its effects on different target cells by interacting with a specific receptor. This interaction leads to the association and activation of a second membrane glycoprotein, gp130, which is the IL-6 signal transducing molecule. The nucleotide sequence of gp130 from a human B-cell line has been reported. We report here the cloning and sequence analysis of the gp130 molecule derived from rat liver. Comparison of gp130 molecules from the different species and cell types reveals 78% overall amino acid homology and 94% identity in the growth factor signaling domain. Two gp130 mRNA species, a moderately abundant species of 7.5 kb and a lesser one of 9.0 kb, were present in rat hepatocytes. Ribonuclease protection analyses demonstrated the presence of gp130 mRNA in four different nontransformed cell types: hepatocytes, astrocytes, fibroblasts, and endothelial cells. The sequences between both gp130s in the different cell types are quite similar, supporting the prediction that the different responses initiated by IL-6 on different target cells are modulated by cell-specific proteins distal to the activated gp130 molecule. PMID- 1427894 TI - A testis-expressed Zn finger gene (ZNF76) in human 6p21.3 centromeric to the MHC is closely linked to the human homolog of the t-complex gene tcp-11. AB - A novel testis-expressed Zn finger gene (ZNF76) was identified by screening cDNA libraries with cosmids derived from 6p21. ZNF76 is a member of the GLI-Kruppel family of DNA binding proteins. It is conserved in mouse where transcription in testis is initiated at Day 20 after birth. The mouse tcp-11 gene is located in the distal inversion of the t-complex and is developmentally regulated in the same manner as ZNF76. The human homolog of tcp-11 was isolated to allow a precise chromosomal localization. By using a combination of somatic cell hybrids, radiation hybrids, metaphase and interphase fluorescent in situ hybridization, and pulsed-field gel electrophoresis, we mapped the two genes to the 6p21.2 to 6p21.3 region and linked them to each other within 300 kb of DNA, approximately 2 Mb centromeric to the major histocompatibility complex. PMID- 1427895 TI - Rapid generation of region-specific genomic clones by chromosome microdissection: isolation of DNA from a region frequently deleted in malignant melanoma. AB - Malignant melanoma is frequently characterized by the deletion of the long arm of chromosome 6 (usually encompassing 6q16-q21). In an effort to saturate this region with DNA markers, microdissection and molecular cloning of DNA from banded human metaphases recent development of a novel chromosome microdissection scheme that omits microchemical manipulation of DNA. Microdissection was targeted on band 6q21. Direct PCR amplification of dissected DNA was first used as a probe in chromosomal in situ hybridization of normal metaphases to confirm the specificity of material excised for cloning. A genomic library of 20,000 clones, which is highly enriched for sequences encompassing 6q21, was then constructed. Clones from this library have been mapped against a human-rodent somatic cell hybrid mapping panel that divides chromosome 6 into seven regions, confirming the localization of probes within the target region. Direct PCR amplification of DNA excised by microdissection greatly simplifies and facilitates this chromosome band-specific cloning strategy. The isolation of microclones from this region of chromosome 6 should assist in establishing a physical map of the melanoma deletion region. PMID- 1427896 TI - Assignment of the genes encoding human interleukin-8 receptor types 1 and 2 and an interleukin-8 receptor pseudogene to chromosome 2q35. AB - Two human cDNA clones that encode different interleukin-8 (IL8) receptors have recently been isolated. The interleukin-8 receptor type 1 (IL8R1) binds IL8 only, whereas the interleukin-8 receptor type 2 (IL8R2) (previously designated IL8RA) also binds growth regulated gene (GRO), and neutrophil activating protein-2 (NAP 2) with high affinity. In the process of screening a genomic library with these cDNAs to obtain large clones for use in chromosomal localization studies, we isolated an interleukin-8 receptor pseudogene (IL8RP) that bears greatest similarity to IL8R2. Using Southern hybridization analysis of human x rodent somatic cell hybrid DNAs with cDNA probes for IL8R1 and IL8R2 and probes from the IL8RP locus, we assigned the three loci to chromosome 2; fluorescence in situ hybridization (FISH) to metaphase chromosome preparations using genomic clones from each locus refined this localization to chromosome 2, band q35, for all three. By virtue of their chromosomal location, IL8R1 and IL8R2 may be considered candidate genes for several human disorders in which the involved locus has been mapped to distal 2q or that are associated with structural abnormalities of this segment, including van der Woude syndrome and the neoplastic diseases rhabdomyosarcoma and uterine leiomyomata. In addition, because this region of chromosome 2q is homologous to proximal mouse chromosome 1 in the segment containing the Lsh-Ity-Bcg locus involved in mediating host resistance to infection with intracellular pathogens, examination for abnormalities of the murine homologues of the IL8R genes should be considered in mice affected by mutations of this locus. PMID- 1427897 TI - Comparison of five tandem repeat loci between humans and chimpanzees. AB - Five tandem repeat loci were studied in humans and chimpanzees using VNTR probes derived from human DNA. Shared alleles were found at three loci and were often the modal allele in one species but never in both. There was no difference in the mean number of alleles per locus. However, these species exhibited substantially different levels of gene diversity, with chimpanzees monomorphic at two loci. Evidence of reduced variability in chimpanzees corroborates earlier comparisons using isozymes and plasma proteins. Molecular mechanisms, population dynamics, or both may be responsible for these differences. Equal numbers of alleles per locus may reflect high mutation rates. By one test, chimpanzees were out of equilibrium at one locus, which may reflect a typing error or population substructure. The long divergence time, and the high probability of backward mutations, precludes accurate estimation of genetic distance between these species. PMID- 1427898 TI - Linkage studies of Usher syndrome type 1: exclusion results from the Usher syndrome consortium. AB - Usher Syndrome Type 1 is an autosomal recessive disease characterized by profound congenital hearing impairement and vestibular dysfunction followed by the onset of retinitis pigmentosa in childhood or early adolescence. Members of the Usher Syndrome Consortium, whose objective is to locate and isolate the genes for Usher syndrome, have pooled linkage data from 36 families with 111 affected individuals. We report the analysis of 206 blood group, protein, and DNA marker polymorphisms. No evidence of linkage heterogeneity among families was found for any of the markers studied; the negative lod scores exclude the locus for this disease from about 39% of the genome. Our results indicate the regions of the genome to which our continuing efforts should be directed. PMID- 1427899 TI - A genetic linkage map of human chromosome 9q. AB - A genetic linkage map of human chromosome 9q, spanning a sex-equal distance of 125 cM, has been developed by genotyping 26 loci in the Venezuelan Reference Pedigree. The loci include 12 anonymous microsatellite markers reported by Kwiatkowski et al. (1992), several classical systems previously assigned to chromosome 9q, and polymorphisms for the genes tenacin (HXB), gelsolin (GSN), adenylate kinase 1 (AK1), arginosuccinate synthetase (ASS), ABL oncogene (ABL1), ABO blood group (ABO), and dopamine beta-hydroxylase (DBH). Only a marginally significant sex difference is found along the entire length of the map and results from one interval, between D9S58 and D9S59, that displays an excess of female recombination. A comparison of the genetic map to the existing physical data suggests that there is increased recombination in the 9q34 region with a recombination event occurring every 125-400 kb. This map should be useful in further characterizing the relationship between physical distance and genetic distance, as well as for genetic linkage studies of diseases that map to chromosome 9q, including multiple self-healing squamous epithelioma (MSSE), Gorlin syndrome (NBCCS), xeroderma pigmentosum (XPA), nail-patella syndrome (NPS1), torsion dystonia (DYT1), and tuberous sclerosis (TSC1). PMID- 1427900 TI - Fingerprinting human chromosomes by polymerase chain reaction-mediated DNA amplification. AB - We describe here a method for DNA fingerprinting of human chromosomes by Alu polymerase chain reaction (PCR) amplification of DNA from monochromosomal hybrids, following digestion with restriction endonucleases. DNA digestion with restriction enzymes prior to PCR amplification reduces the total number of amplified fragments. The number and pattern of bands of PCR products observed in an electrophoretic medium are chromosome specific and provide a "fingerprint signature" for individual human chromosomes. Using this approach, we have produced fingerprints for human chromosomes 2, 5, 7, 9, and 12. The applicability of this approach to chromosome identification was assessed by comparing the fingerprints obtained for two different hybrids containing chromosome 7. DNA fragments specific for the long and the short arms of human chromosome 12 have also been identified. In addition, Alu-PCR-generated DNA fragments, specific for different chromosomes, were used to probe Southern blots of a hybrid cell panel to identify human chromosomes present in hybrid cell lines. The chromosomal specificity of these probes permits the identification of intact as well as rearranged chromosomes composed of segments arising from more than one chromosome. PMID- 1427902 TI - High-resolution physical mapping of four microsatellite repeat markers near the RYR1 locus on chromosome 19q13.1 and apparent exclusion of the MHS locus from this region in two malignant hyperthermia susceptible families. AB - Malignant hyperthermia susceptibility (MHS) is a potentially lethal, hereditary disorder of skeletal muscle that may be triggered by inhalation anesthetics and depolarizing muscle relaxants. Defects in the gene encoding the ryanodine receptor (RYR1) localized on human chromosome 19q13.1 have been proposed to be responsible for MHS. Using a chromosome 19-specific human/hamster somatic cell hybrid mapping panel, we were able to determine that four closely linked microsatellite repeat markers bracket RYR1 with the order 19cen-D19S75-D19S191 RYR1-(D19S47, D19S190)-19ter. Application of the four markers to genetic studies of MHS showed recombination between the markers and MHS in two families, with linkage analysis apparently excluding the MHS locus from the RYR1 region of 19q13.1. These results therefore support the recent observations of genetic heterogeneity in MHS. PMID- 1427901 TI - A new method for constructing NotI linking and boundary libraries using a restriction trapper. AB - We have developed a novel method for constructing NotI linking and boundary libraries using a modified "solid-supported ligation primer" (restriction trapper). The restriction trapper could be used to purify the DNA fragments with a specific restriction enzyme cutting site(s) at their ends. The method uses a ligation and recutting reaction with double-stranded DNA ends of a hairpin-shaped oligolinker which is connected covalently to the surface of the latex beads. Selectivity is based on the specificity of the restriction enzyme for its recognition site, resulting in efficient purification. We applied this technique to the construction of high-quality NotI linking and NotI boundary libraries, which contain almost all the NotI sites of the genome and, in addition, are free of illegitimately ligated clones. PMID- 1427903 TI - Localization of the gene encoding the alpha subunit of human interleukin-5 receptor (IL5RA) to chromosome region 3p24-3p26. AB - The chromosomal location of the human gene for the alpha subunit of interleukin-5 receptor (IL5RA) has been determined. The human IL5RA gene was localized to the short arm of chromosome 3 by Southern blot analysis of DNA from a panel of mouse human hybrid somatic cell lines. The IL5RA gene has been further localized to human chromosome region 3p24-3p26 by in situ hybridization of a molecularly cloned IL5RA cDNA fragment to metaphase chromosomes. The results suggest that the IL5RA locus is unlinked to other members of the hematopoietic receptor family. Assignment of the IL5RA gene to chromosome 3 at bands p26-p24 raises the possibility that it may be altered by certain nonrandom chromosomal abnormalities arising in human hematopoietic malignancies and solid tumors. PMID- 1427904 TI - A bone morphogenetic protein subfamily: chromosomal localization of human genes for BMP5, BMP6, and BMP7. AB - Bone morphogenetic proteins (BMPs) were originally identified by the ability of a demineralized bone extract to induce endochondral osteogenesis in vivo. Seven BMP cDNAs (BMP1 through BMP7) have been recovered through molecular cloning. Recombinant protein products from six of these clones (BMP2 through BMP7) are members of the transforming growth factor beta (TGF-beta) superfamily of regulatory molecules. Based upon a high degree of amino acid sequence homology, BMP5, BMP6, and BMP7 constitute a subfamily within the BMPs. Using human-rodent somatic cell hybrid lines and cDNA probes, we mapped the three members of this subfamily of genes to the human chromosomes. BMP5 and BMP6 are syntenic on human chromosome 6, while BMP7 is syntenic with previously localized BMP2 on human chromosome 20. This analysis reveals that BMP6 maps to a conserved region between the mouse and human genomes. Sequence analysis suggests that the Drosophila 60A gene is the dipteran homolog of this BMP subfamily and may provide clues to the physiologic functions of the products of these genes in human biology. PMID- 1427905 TI - Construction and characterization of a region-specific microdissection library from human chromosome 2q35-q37. AB - A region-specific genomic library for human chromosome 2q35-q37 has been constructed using the microdissection and polymerase chain reaction-mediated linker-adaptor microcloning method. Twenty fragments from the chromosome region 2q35-q37 were dissected and a library consisting of 20,000 recombinant microclones was obtained. The insert size ranged between 50 and 800 bp, with a mean of approximately 270 bp. About 50-60% of the microclones contained unique sequences. The microdissection library has been demonstrated to derive from the dissected region 2q35-q37 by chromosome painting using the fluorescence in situ hybridization (FISH) technique. Southern blot analysis of the unique sequence microclones from the library showed that 54% (26/48) of the clones are of human origin and chromosome 2 specific. Four of these microclones have been further mapped to the 2q37 region by using a cell hybrid containing only 2q37. The unique sequence microclones have also been characterized for their insert size and the hybridizing genomic fragments cleaved with HindIII. As shown previously, these microclones will be useful in isolating corresponding yeast artificial chromosome (YAC) clones with large inserts for high-resolution physical mapping and also in screening cDNA libraries to isolate expressed gene sequences as candidate genes to facilitate search for the crucial genes underlying genetic diseases and specific forms of cancer assigned to the region. PMID- 1427906 TI - Subregional mapping of 13 single-copy genes on the long arm of chromosome 12 by fluorescence in situ hybridization. AB - Subregional localization of 13 single-copy DNA sequences previously assigned to the long arm of chromosome 12 has been performed using the fluorescence in situ hybridization (FISH) technique. The following order is suggested for the 13 mapped genes: cen-->COL2A1-->(VDR-D12S15)-->(D12S17-D12S4++ +-D12S14-D12S6)- >D12S8-->(IAPP-MGF- D12S7-D12S12)-->IGF1-->qter. Eight of the mapped genes clustered at two regions, one at 12q13 (D12S17-D12S4-D12S14-D12S6) and the other at 12q22 (IAPP-MGF-D12S7-D12S12). Our results show that single-copy DNA sequences as small as 500 bp can be successfully mapped by FISH. PMID- 1427907 TI - Localization of the human KRAB finger gene ZNF117 (HPF9) to chromosome 7q11.2. AB - A cluster of Kruppel type zinc finger genes of the KRAB subclass has recently been localized on human chromosome 19p12-p13.1. We now report that ZNF117 (HPF9), a closely related zinc finger gene of this KRAB subfamily, has been assigned to a distinct locus in the human genome: chromosome band 7q11.2. PMID- 1427908 TI - The gene for tissue inhibitor of metalloproteinases-2 is localized on human chromosome arm 17q25. AB - Tissue inhibitor of metalloproteinases-2 (TIMP2) is a natural inhibitor of several proteinases that are involved in the degradation of the extracellular matrix. By means of somatic cell hybrids segregating human chromosomes, the gene encoding this inhibitor was assigned to human chromosome 17. Fluorescence in situ hybridization confirmed this assignment and allowed mapping of the gene to the terminal region (17q25) of the chromosome. PMID- 1427909 TI - Autosomal localization of the amelogenin gene in monotremes and marsupials: implications for mammalian sex chromosome evolution. AB - We have determined by Southern blot analysis that DNA sequences homologous to the AMG gene probe are present in the genomes of both marsupial and monotreme mammals, although adult monotremes lack teeth. In situ hybridization and Southern analysis of cell hybrids demonstrate that AMG homologues are located on autosomes. In the Tammar Wallaby, AMG homologues are located on chromosomes 5q and 1q and in the Platypus, on chromosomes 1 and 2. The autosomal location of the AMG homologues provides additional support for the hypothesis that an autosomal region equivalent to the human Xp was translocated to the X chromosome in the Eutheria after the divergence of the marsupials 150 million years ago. The region containing the AMG gene is therefore likely to have been added 80-150 million years ago to a pseudoautosomal region shared by the ancestral eutherian X and Y chromosome; the X and Y alleles must have begun diverging after this date. PMID- 1427910 TI - Assignment of a novel protein tyrosine phosphatase gene (Hcph) to mouse chromosome 6. AB - Hematopoietic cell phosphatase (Hcph) was identified by amplification of conserved protein tyrosine phosphatase sequences from a myeloid cell line and is predominantly expressed in hematopoietic cells. Hcph is unique in containing two, tandemly repeated, src-homology 2 domains in the amino terminal region of the phosphatase. Using a genomic probe in interspecific backcross analysis, the murine Hcph gene maps to mouse Chromosome 6 and is tightly linked to the Tnfr-2 and Ly-4 genes. PMID- 1427911 TI - Identification of a processed pseudogene related to the functional gene encoding the GM2 activator protein: localization of the pseudogene to human chromosome 3 and the functional gene to human chromosome 5. AB - The GM2 activator protein is an essential substrate cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A (EC 3.2.1.52). There have been conflicting reports as to the chromosomal localization of the gene encoding the activator. We demonstrate here that these conflicts were caused by the presence of a previously unidentified processed activator-pseudogene on chromosome 3, and we confirm a previous ELISA-based localization of the functional activator gene to chromosome 5. Our data indicate that the functional activator locus can still be considered a candidate site for defects causing some forms of spinal muscular atrophy. PMID- 1427912 TI - Autosomal dominant retinitis pigmentosa: a novel mutation at the peripherin/RDS locus in the original 6p-linked pedigree. AB - Using single-strand conformation polymorphism electrophoresis, heteroduplex analysis, and direct sequencing, we have searched for possible disease-causing mutations in the adRP family in which we originally found tight linkage of the disease to 6p. We have now identified a single base change in exon 2, which results in the replacement of a serine residue at codon 212 for a glycine residue. The mutation cosegregates with the disease with a lod score of 12.1 at theta = 0.0. PMID- 1427913 TI - Chromosomal assignment of 38 human brain expressed sequence tags (ESTs) by analyzing fluorescently labeled PCR products from hybrid cell panels. AB - We have localized 38 human brain cDNA sequences to individual human chromosomes. PCR primers were designed from expressed sequence tags and tested for specific amplification from human genomic DNA. The sizes of amplification products from DNA of somatic cell hybrid mapping panels were determined electrophoretically using an automated fluorescence detection system. Chromosomal assignments were made by discordancy analysis. PMID- 1427914 TI - Evidence for nonallelic genetic heterogeneity in autosomal recessive retinitis pigmentosa. AB - Recent evidence suggesting the involvement of mutant rhodopsin proteins in the pathogenesis of autosomal recessive retinitis pigmentosa has prompted us to investigate whether this form of the disease shows non-allelic genetic heterogeneity, as has previously been shown to be the case in autosomal dominant retinitis pigmentosa. The availability of a unique inbred Dutch pedigree has enabled us to address this question. We have used an intragenic polymorphism to exclude the possibility that a mutation in the rhodopsin gene is responsible for the disease in this patient population. These data provide evidence for the involvement of at least two loci in autosomal recessively inherited retinitis pigmentosa. PMID- 1427915 TI - Dinucleotide repeat (GT)n markers on chromosome 21. AB - To further develop the linkage map of human chromosome 21 (HC21), we have concentrated on identifying highly polymorphic markers based on dinucleotide repeat sequences such as (GT)n, as these are often highly polymorphic, are widespread throughout the human genome, and can be rapidly analyzed by the polymerase chain reaction. We report here nine (GT)n polymorphic markers from HC21. PMID- 1427916 TI - Regional localization of the highly polymorphic locus D11S533 on the linkage map of human chromosome 11q. PMID- 1427917 TI - Sublocalization of the gene encoding manganese superoxide dismutase (MnSOD/SOD2) to 6q25 by fluorescence in situ hybridization and somatic cell hybrid mapping. PMID- 1427918 TI - PCR-based detection of two exonic polymorphisms in the human type VII collagen gene (COL7A1) at 3p21.1. PMID- 1427919 TI - Linkage analysis demonstrates that the Timp-2 locus is on mouse chromosome 11. PMID- 1427920 TI - VH-gene representation in autoantibodies reflects the normal human B-cell repertoire. AB - The recurrence in the V-gene repertoire of individual germline VH genes can now be extended from the restricted B-cell populations of the fetus, autoantibodies and B-cell malignancies to the expressed V-gene repertoire of normal adults. Why the human B cell preferentially utilizes these individual VH genes remains speculative. However, it is apparent that the population of VH genes used to encode autoantibodies reflects the normal expressed repertoire (Fig. 7). Even so, the overrepresentation of other V genes such as Dxp'1 in anti-DNA antibodies and the presence of somatic mutation in the pathogenic autoantibodies of autoimmune disease continues to suggest an antigenic influence on V-gene selection. We postulate that only a fraction of available germline V genes are utilized in the expressed repertoire, and that polyspecificity of naturally occurring antibodies and somatic mutation of CDR3 compensate for the loss of diversity entailed by the limited use of the potential repertoire. The mechanisms by which germline genes become pathogenic remains unclear but they presumably relate to mutation, loss of regulatory control or perhaps environmental factors (Isenberg et al. 1992). What then are the mechanisms which lead to escape of these VH genes from normal control? What antigenic drive if any produces anti-DNA specificity in SLE? Why indeed is the expressed repertoire using only a fraction of the available germline? To answer these questions, further study of the V-gene repertoire of selected populations of antigen-binding cells and of pathogenic IgG autoantibodies is necessary and is ongoing. The contribution of individual V genes to antigen binding and idiotype is also being dissected and promises to yield important information about the relative contribution of VH genes to autoimmunity. PMID- 1427921 TI - Selection of immunoglobulin variable regions in autoimmunity to DNA. AB - Results from our analyses of variable region gene usage among spontaneous anti DNA antibodies in autoimmune mice have indicated that both the early IgM and later-appearing IgG autoantibodies to DNA are generated by clonally selected B cells. The recurrent usage of particular variable region genes among all the anti DNA hybridomas analyzed and reported to date supports this hypothesis. The preferential expression of particular light and heavy chain variable region genes among selected populations of both IgM and IgG anti-DNA hybridomas likewise supports the hypothesis. Both IgM and IgG antibody-producing B cells are derived from the same clonal precursor population and may be derived from the same B cell clonal precursor within an individual mouse. The selective and recurrent expression of germline and somatically-derived structures that would be expected to promote protein binding to DNA within anti-DNA antibody variable regions, particularly arginines in both light and heavy chain complementarity-determining regions, indicates that DNA or DNA-containing complexes may be the antigen that stimulates anti-DNA antibody in autoimmune mice. The progressive increase in the specificity of spontaneous anti-DNA antibodies for native DNA as the autoimmune response matures from IgM to IgG likewise suggests that DNA may be the antigenic stimulus for spontaneous anti-DNA in autoimmune mice. A hypothetical, computer generated model of anti-DNA antibody binding to DNA provides an interesting paradigm for the molecular basis of antibody specificity for DNA. PMID- 1427923 TI - Mouse variable-region gene families: complexity, polymorphism and use in non autoimmune responses. PMID- 1427922 TI - Rheumatoid factor V genes from patients with rheumatoid arthritis are diverse and show evidence of an antigen-driven response. PMID- 1427924 TI - Development of human antibody variable genes in systemic autoimmunity. PMID- 1427925 TI - Antegrade and retrograde cardioplegia with different reperfusion techniques in patients with multiple coronary artery lesions. AB - To evaluate the effectiveness of retrograde cardioplegia and reperfusion, a total of 266 patients undergoing coronary bypass surgery between Nov 1987 to Dec 1989 were divided into three groups depending on the method of cardioplegic fluid delivery and reperfusion. In group I (80 patients) antegrade cardioplegia and reperfusion was used. In group II (98 patients) antegrade and retrograde cardioplegia and antegrade reperfusion was used while in group III antegrade and retrograde cardioplegia and retrograde reperfusion was used. Myocardial functions were studied with the help of an on-line computer on the basis of mathematical model of heart before and after cardiopulmonary bypass. Biopsy specimens were collected before, during and after cardiopulmonary bypass in order to study myocardial structural changes. In group I patients there was decrease in myocardial function in the immediate post perfusion period while group II patients had considerable improvement in their myocardial function and groups III patients showed further improvement in it. Ultrastructural myocardial study revealed considerable detrimental changes in group I, minimal changes in group II and no change in group III patients. Thus in our experience retrograde cardioplegia and retrograde reperfusion with warm oxygenated blood provide maximum myocardial protection in patients with multiple coronary artery lesions. PMID- 1427927 TI - ECG patterns in right sided chest leads in normal persons. PMID- 1427926 TI - Cannulation of the internal jugular vein in patients undergoing open heart surgery. AB - A total of 476 internal jugular vein cannulations performed between June 1990 to August 1991 were prospectively evaluated. The patients' age ranged between ten days to 61 years. We achieved a high success rate of cannulation (97.9%). We describe the use of two single lumen catheters inserted through right internal jugular vein as an alternative to the popular multilumen catheters. We also suggest that low approach should be tried more often in children, if the central approach fails. PMID- 1427928 TI - Diastolic collapse of both atria in patients of cardiac tamponade: report of two cases. PMID- 1427929 TI - Bilateral coronary artery to pulmonary artery fistulae: angiographic and echocardiographic report. PMID- 1427931 TI - Dr. S. Padmavati awarded Padma Vibhushan. PMID- 1427930 TI - Isolated type A aortic arch interruption in an adult female. PMID- 1427932 TI - Balloon catheter therapy for valvular heart disease: the state of the art. PMID- 1427933 TI - Long term results of percutaneous transluminal valvuloplasty in patients with valvular aortic stenosis. AB - The results of percutaneous balloon aortic valvuloplasty (PBAV) in 62 consecutive patients with valvular aortic stenosis are reported. The age of the patients ranged from 11 months to 72 years (mean 28 +/- 12 years). Hemodynamically successful dilatation was achieved in 58 out of 62 patients. This was associated with marked clinical improvement in these patients. The left ventricular aortic peak to peak gradient decreased from 96.67 +/- 38.4 to 28.14 +/- 26.5mmHg (p < 0.01). There were no deaths during the procedure. Only one patient died in the hospital during the same admission. There was an increase in aortic regurgitation (AR) by at least one grade in 25 (40.3%) patients. Femoral arterial thrombosis was seen in 9/62 patients, 5 of them requiring surgical intervention. Follow up was available in 28 (45.1%) patients over a period of 2-15 months (mean 9 +/- 3 months). Two patients died during the follow up period. Doppler evaluation of gradients was done in all 28 patients with 15 consenting to undergo repeat cardiac catheterisation. Although hemodynamically the restenosis rate was 35.7% (10/28), only 2 of these patients showed symptomatic deterioration. The success of dilatation and restenosis rate were independent of the etiology of aortic stenosis, presence of calcification and the number of balloons used. This study demonstrates that PBAV is feasible in valvular aortic stenosis at low risk and is able to produce significant clinical and hemodynamic improvement in most cases with a restenosis rate of 35.7% at a follow up period of 9 +/- 3 months. PMID- 1427934 TI - High risk coronary angioplasty using percutaneous cardiopulmonary bypass support. AB - Twenty high risk patients with severe angina were subjected to balloon angioplasty after instituting percutaneous cardiopulmonary bypass support to enhance the safety of high risk elective coronary angioplasty. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the targeted artery or both (left ventricular ejection fraction < or = 25% in 15 patients). Three vessel disease was present in all. Angioplasty of the only remaining vessel was done in 14 patients, 2 vessels in 5 patients and a sequential graft in 1 patient. Bypass flows ranged from 2.8-4.5 litres. Bypass was discontinued after a mean bypass time of 35 min. Haemostasis was achieved by external clamp compression in 16 patients. The angioplasty was successfully performed in all the patients and the procedure was well tolerated. During the bypass period the pulmonary artery diastolic pressures ranged from 0-8 mm Hg. There was 1 hospital death due to abrupt vessel closure. Two patients required surgical help to repair femoral artery. During the follow up period of 1-12 months, 67% patients have no angina and only 1 has died. Our experience demonstrates the safety and efficacy of percutaneous bypass support in selected patients undergoing high risk coronary angioplasty. PMID- 1427935 TI - Percutaneous transluminal coronary angioplasty in patients over the age of 65 years. AB - PTCA performed in 672 patients (646 patients < 65 years and 26 patients > or = 65 years) from March 1986 to September 1990 consisting of 619 males and 53 females are being discussed for the purpose of comparison of the results between patients in the < 65 years and > or = 65 years age groups. It was found that diabetes mellitus (50 vs 24.4.%, P < 0.01), obesity (46.1 vs 26%, P < 0.05), and hyperlipidaemia (66 vs 37.1%, p < 0.01) had a higher incidence among the elderly. Of the total 1047 lesions observed, 662 lesions in the < 65 years age group and 37 lesions in the > or = 65 years age group were dilated by PTCA (1.02 lesions/patient and 1.4 lesions/patient respectively). The lesion morphology showed higher degree of irregular contour in the < 65 years age group (23.6 vs 8.1%, p < 0.05), though the number of lesions with PTCA attempted in all age groups were almost similar. Major complications included one MI (3.8%) and two deaths (7.6%) in the > or = 65 years age group. During followup (mean duration: 8.2 months > or = 65 years and 13.5 months < 65 years age group) significantly higher percentage of patients < 65 years were asymptomatic when compared to elderly (50.2 vs 15.4% p < 0.05). Angina status was same more often in the elderly (23.1 vs 2.8% p < 0.01). The cumulative rate for repeat PTCA was similar for elderly and younger patients. PMID- 1427937 TI - Modified cephalic vein guide wire technique for permanent pacemaker implantation. AB - This report describes a modified cephalic vein guide wire technique used for implantation of 18 consecutive pacemakers using bipolar leads. The modified technique appears to be a safe and simple procedure for single chamber permanent pacing. Its use may also be extended in implanting dual chamber pacemakers. PMID- 1427936 TI - Acute hemodynamic effects of different atrioventricular intervals in dual chamber pacemakers: is there an optimum atrioventricular delay. AB - Conflicting data have been reported regarding adjustment of atrioventricular (AV) interval to maximise hemodynamic performance of dual chamber pacemakers. Eleven consecutive patients with complete heart block and dual chamber pacemakers were paced at three AV intervals (150, 200, 250 msec) and free running rates (60-93 bpm, mean 73 +/- 12 bpm) with simultaneous measurements of cardiac output, atrial contribution to left ventricular filling, left ventricular ejection fraction, and peak aortic velocity and acceleration by echo-Doppler techniques to define the optimum AV delay. At all the three AV intervals tested there was no difference in cardiac output (4.7 +/- 0.96, 4.83 +/- 1.12, 4.77 +/- 1.19 litres/min respectively, p = NS), left ventricular ejection fraction (60.2 +/- 10.6%, 61.2 +/- 9.9% and 64 +/- 8.3%, p = NS), atrial contribution to left ventricular filling (0.37 +/- 0.10, 0.38 +/- 0.09, 0.36 +/- 0.16, n = 8, p = NS), peak aortic velocity (104 +/- 8, 105 +/- 12, 104 +/- 13 cm/sec, p = NS) and aortic acceleration (19.68 +/- 4.26, 20.4 +/- 5.58 and 19.0 +/- 4.54 m/sec2, p = NS). Compared to AV delay of 150 msec an increase in cardiac output of 0.5 L/minute was observed in three patients at an AV delay of 200 msec and in one patient at the AV delay of 250 msec. These data suggest that it is difficult to generalize an optimum AV delay in patients with dual chamber pacemakers. With the AV interval in the range of 150-250 msec, only a minority of patients could improve their haemodynamics at rest by adjusting this interval if the baseline cardiac function was normal. PMID- 1427939 TI - Asymptomatic coronary heart disease detected on epidemiological survey of urban population of Delhi. AB - A community based epidemiological study of coronary heart disease (CHD) was carried out in a random sample of 13723 adults in the age group of 25-64 years in the urban population of Delhi. The electrocardiogram (ECG) of all clinically detected CHD cases and of a sample of 5621 persons (selected on the basis of alternate household screened) without clinical manifestations of CHD, was obtained. Out of 5621 persons labelled as asymptomatic, CHD evidence of Q wave myocardial infarction (MI) was present in 80 ECGs (1.4%). Another 296 ECGs had ST & T changes vide Minnesota Code 4-1-1, 4-1-2, 5-1 and 5-2 acceptable as evidence of probable CHD. The overall prevalence rate of asymptomatic CHD was 6.7% (male 5.6%, female 7.6%). Silent MI was more common in the male patients (1.7% vs 1.1%, p < 0.001). However, ST-T changes were more common in female patients (6.5% vs 3.9%, p < 0.001). The ST-T changes showed a steady factor in asymptomatic CHD cases was hypertension in both sexes (male-45.2%, female-43.5%) p = NS. Obesity was present in 24% of male & 46.1% of female patients (p < 0.001). Family history was found in 20% cases of both sexes. Smoking was recorded in 34.9% male and 10.9% female patients with asymptomatic CHD (p < 0.001). PMID- 1427938 TI - Experience with recycled cardiac pacemakers. AB - Twelve years experience with pacemaker re-use is reported. Between November 1979 and December 1991, forty two pacemakers were re-used in 42 patients after in hospital reconditioning. There were 31 males and 11 females in the age range of 29 to 84 years (mean 59 +/- 13 years). In 29 patients, the pulse generator was explanted because of pocket infection and/or impending extrusion, and it was re implanted at a new site after sterilization. In the remaining 13 patients pacemakers explanted from other patients were implanted because of economic reasons. All patients were regularly followed up in the pacemaker clinic for a mean duration of 34 +/- 35 months (range 6-126 months). There was one infection and one erosion after 12 and 27 months respectively. One of these units was resterilized and implanted without any recurrence of infection or erosion over a follow up of 12 months. There was no adverse reaction or pulse generator failure. Our experience suggests that the use of refurbished pacemakers is a safe and economically viable option. PMID- 1427940 TI - Coronary artery disease in premenopausal Indian women: risk factors and angiographic profile. AB - Coronary angiographic and clinical profile of 47 premenopausal women presenting with myocardial infarction (MI) or angina is presented. Seventeen patients (36%) had significant obstructive coronary artery disease (CAD) (Group I), while 30 (64%) had normal coronaries (Group II). The latter group included 4 who had MI and 26 who presented with angina. Risk factors in Group I included hypertension (53%), diabetes mellitus (24%), hypercholesterolemia (29%), oral contraceptives and a positive family history (11.8%). Frequency of one, two and three vessel disease was 47%, 18% and 35% respectively. The left anterior descending artery was most commonly affected (82%). In Group II the risk factors included hypertension (17%) and diabetes (7%). No patient in either group was a smoker. This analysis shows that significant obstructive CAD in premenopausal Indian females is more commonly associated with hypertension, diabetes and hypercholesterolemia. Smoking was not encountered and ingestion of contraceptive pills is uncommon. PMID- 1427941 TI - Closure of congenital and acquired intracardiac shunts using transcatheter techniques: a review. PMID- 1427943 TI - Thrombolytic therapy in acute evolving myocardial infarction--widening the net. PMID- 1427942 TI - Feasibility of thrombolytic therapy--a one year prospective study. AB - A one year prospective study was conducted on all the patients admitted with clinical diagnosis of acute myocardial infarction (AMI) to determine the proportion of patients who can be given thrombolytic therapy. Factors responsible for non-administration were analysed. 213 patients with AMI entered the study. Standard inclusion criteria for thrombolytic therapy were used. 101 (47%) patients failed to meet the inclusion criteria. This included 7 (3.3%) who failed to satisfy the electrocardiographic (ECG) criteria. Nine patients with atypical symptoms were unable to reach within the stipulated 6 hours while the remaining 85 (40%) patients were delayed inspite of typical features due to inability of the patient to attribute the symptoms to the heart, lack of proper transport facility and self medication. 112 patients (53%) met the inclusion criteria but 7 patients were excluded because of age (> 70 years), and another 8 because of contraindications. Of the remaining 97 patients, 47 failed to receive thrombolytic therapy due to lack of awareness of the benefits of thrombolytic therapy by the first treating physician, misinterpretation of ECG, inability to afford and refusal to give consent. Only 50 patients (23%) received thrombolytic therapy. This low figure can be easily improved upon by the correction of a number of remediable factors. PMID- 1427944 TI - Early experience with coronary stenting. AB - From April 1988 to December 1991, we implanted 75 coronary stents (29 self expanding and 46 balloon expandable) in 62 patients. All had New York Heart Association class II to IV angina, and 11 (18%) had prior coronary artery bypass grafting (CABG). Thirty nine patients (63%) had 1 vessel disease, and 23 (37%) had multivessel disease. The mean left ventricular ejection fraction was 63 +/- 11%. The indications for coronary stenting were acute post percutaneous transluminal coronary angioplasty (PTCA) occlusion in 45 (73%) (bail out stenting) and restenosis in 17 (24%) (elective stenting). There were 52 single stent (84%), 7 double stent (11%), and 3 triple stent procedures (5%). The mean stent diameter was 3.8 +/- 0.5 mm, and the mean stent length 21 +/- 7 mm. The attempted vessels were the left main coronary artery in 2(3%), left anterior descending coronary artery in 27 (44%), left circumflex coronary artery in 8 (13%), right coronary artery in 17 (27%), and a saphenous vein graft in 8 (13%). Technical success was achieved in 74 stent implantations (98%). Technical failure occurred in 1 case with a self expanding stent because of inability to reach the lesion. In hospital complications (mean hospital stay 10 +/- 10, range 2-60 days) included temporary stent occlusion in 2 patients (3%) treated by balloon dilatation and thrombolysis with intravenous urokinase, permanent stent occlusion in 5 patients (8%), Q-wave infarction in 5 patients (8%), CABG in 4 patients (11%), and death in 3 patients (5%). At least 1 major complication (Q wave infarction, CABG, or death) occurred in 8 patients (13%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1427945 TI - Long term performance of silicone insulated and polyurethane insulated cardiac pacing leads. AB - The long term performance of various pacing leads in use for at least one year is reported from one centre. Between January 1975 and December 1990, 1056 cardiac pacing leads were implanted in 881 patients (mean age 57 +/- 13 years). Eight hundred and three leads were silicone insulated (SI) and 253 leads were polyurethane insulated (PUI). Leads from different manufacturers were used (Medtronic, CPI, Telectronics). The average duration of follow up was 56.6 +/- 77 months (range 12-221 months) for SI and 47.1 +/- 24 months (range 12-99 months) for PUI leads. Overall lead failure occurred more often in the PUI group (n = 46, 18.2%) compared to SI group (n = 93, 11.3%, p < 0.025). Majority of lead failures occurred in the first 36 months after implantation. In particular, Medtronic models 6971, 6972 (urethane) and 6901 (silicone) showed higher rate of complications (25.5%, 26.3% and 44.5% respectively). PMID- 1427946 TI - Use of captopril as an isolated agent for the management of stable angina pectoris--a double blind randomised trial. AB - In this double blind randomised placebo controlled study, we investigated the antianginal efficacy of oral captopril in 33 patients of angiographically documented coronary artery disease (chronic stable angina). Apart from sublingual nitrates, all other antianginal drugs were withdrawn. Patients were then evaluated both subjectively by questionnaire and objectively by treadmill stress test. No patient had more than mild hypertension and all patients had good left ventricular function. One group of patients received oral captopril while the other group was given placebo. A repeat assessment was done after six weeks and the results compared with baseline. Anginal attacks decreased from 20.11 +/- 1.86 per week on placebo to 9.92 +/- 1.38 (p < 0.01) on captopril as also the number of sublingual nitrates (18.84 +/- 3.01 to 11.14 +/- 2.94, p < 0.01). Assessment by the treadmill stress test showed that in comparison to the pretreatment test, captopril therapy resulted in a significantly increased exercise duration (6.26 +/- 0.21 to 6.98 +/- 0.31 minutes, p < 0.05), total work done (6.76 +/- 0.26 METS to 7.48 +/- 0.29 METS, p < 0.05). In addition there was a significant increase in time to angina (6.16 +/- 0.18 to 6.85 +/- 0.24 min, p < 0.05) and time to 1mm ST depression (5.18 +/- 0.26 to 6.46 +/- 0.30 min, p < 0.01). We conclude that captopril is an effective monotherapy for patients with chronic stable angina and has both antianginal as well as anti-ischemic effects, possibly secondary to direct coronary vasodilation. PMID- 1427947 TI - Colour Doppler echocardiographic quantification of prosthetic aortic valve regurgitation in patients with normally functioning Bjork-Shiley prostheses. AB - Colour Doppler echocardiographic studies were performed in 46 patients (age range 16-35 years, mean 26 +/- 8; male 31, female 15) with normally functioning Bjork Shiley prostheses in aortic position to estimate transprosthetic regurgitation. Regurgitant jet length and height were measured and assessed in multiple views. All patients showed prosthetic regurgitation of varying degree. Regurgitant jets were central in all but 3 (6.5%) patients. Single jets were seen in 28 (61%) and double jets in 18 (39%). Jet height in parasternal long axis view ranged from 0.4 to 1.2 cm (mean 0.7 +/- 0.4 cm) and jet height to left ventricular outflow tract diameter ratio was 0.22 to 0.48 (mean 0.38 +/- 0.13). Prosthetic regurgitation was < or = 2/4 grades in 42 (91%) patients, and combined height of double jets (n = 18) was less than that of the single jets (n = 28) (0.5 +/- 0.3 cm vs 0.8 +/- 0.4 cm, p < 0.05). In conclusion, colour Doppler examination frequently detects prosthetic regurgitation in patients with aortic Bjork-Shiley prostheses; regurgitation is grade 2/4 or less in most of the patients, is overestimated in patients with a single jet and weakly correlates with prosthesis size. PMID- 1427948 TI - Two dimensional and Doppler echocardiographic evaluation of double chambered right ventricle. AB - Two-dimensional and Doppler echocardiographic findings in 20 patients with double chambered right ventricle are described. All patients had the diagnosis established by cardiac catheterisation and confirmed at operation. Echocardiographic evaluation was done prior to surgical correction. Anomalous muscle bands in right ventricular cavity were detected in 16 patients. Doppler flow velocities in the right ventricular cavity suggested infundibular obstruction to blood flow at a low level in all 17 patients studied by Doppler echocardiography. Ventricular septal defects (11 patients), pulmonary stenosis (3 patients), and aortic regurgitation (3 patients) were detected accurately before operation by echocardiographic examination. Failure to detect the anomalous muscles in right ventricular cavity may occur in adult patients with poor anterior resolution and in those with severe right ventricular outflow obstruction and myocardial hypertrophy. Two dimensional echocardiography with Doppler flow analysis is useful in the evaluation and differential diagnosis of right ventricular outflow obstructions prior to invasive studies and surgical intervention. PMID- 1427949 TI - Neonatal pulmonary flow pattern--a pulsed Doppler echo study. AB - The pulmonary flow pattern was analysed by pulsed Doppler in 77 normal neonates, at < 48 hours (36 subjects), 49 to 96 hours (25 subjects) and 97 to 148 hours (16 subjects). From the flow velocity spectrum, using an built in computer system, the acceleration time and the ejection time were measured, and the ratio was calculated. This ratio was 0.24 +/- 0.08 in the subjects within 48 hours whereas this ratio was 0.53 +/- 0.11 in the subjects above 97 hours; thus the ratio increased with age. We noticed that the ratio obtained from the pulsed Doppler is useful in assessing the pulmonary vascular status, even in neonates. PMID- 1427950 TI - Mechanical ventilation after open heart surgery. AB - One hundred adult patients, undergoing elective open heart surgery over a period of 4 months, were studied to assess the practice of ventilation in the post operative period. The anaesthetic technique employed used moderate doses of morphine, supplemented with halothane and a muscle relaxant. The decision to extubate was based on clinical assessment, and satisfactory blood gases following a 45 minute T-piece trial. The patients were ventilated for an average duration of 8 hours and 2 minutes and 59 out of 100 patients were extubated within 8 hours. Patients undergoing coronary artery bypass graft were ventilated for significantly longer durations (10 hours 28 minutes) (p < 0.05) and had significantly lower arterial oxygen tension (p < 0.01) 30 minutes after extubation, as compared with those undergoing valvular surgery. Also patients whose bypass time exceeded 2 hours had significantly longer extubation times (p < 0.05) as compared with those who had a bypass time less than 1 hour. T piece trial was found to be a satisfactory method of weaning in all the patients. PMID- 1427951 TI - The efflux of nor-epinephrine from platelets in genetic hypertension. AB - Platelets have been used as a model of sympathetic neurons to study the storage of nor-adrenaline in normotensive individuals belonging to families with essential hypertension for at least two generations. The efflux and initial efflux rate (K) of noradrenaline was determined in 36 young relatives (mean age 29.2 years) and in 20 young controls with no family history of hypertension (mean age 26.5 years). From the groups of relatives all those with definite hypertension had been excluded. Efflux and efflux rate K was significantly higher in young relatives (50.82 +/- 3.84 and 28.2 +/- 6.3) than in the controls (39.2 +/- 0.71 and 15.2 +/- 4.8). Of the relatives 25.2% had higher K values than any of the controls. PMID- 1427953 TI - About type B Inoue balloon catheters used for percutaneous transvenous mitral commissurotomy. PMID- 1427952 TI - The role of cadmium in induction of atherosclerosis in rabbits. AB - Experiments were carried out in rabbits to determine the effects of prolonged treatment of cadmium (8 mg/kg/day) for a period of 6 months on histopathological changes and biochemical alterations of lipid profiles in various tissues compared to normal rabbits. No ECG changes were observed before and at the end of cadmium treatment. Histopathological studies of the coronary artery revealed atherosclerotic changes. Total lipids, cholesterol, free fatty acids and phospholipids were significantly increased in heart and kidney, but decreased in serum and liver. Triglyceride content was increased significantly in heart and kidney with a significant depletion in liver and serum. It is postulated that atherosclerotic changes in rabbits probably occurred through toxic effects of cadmium but the exact mechanism needs to be elucidated. PMID- 1427954 TI - Rupture of interventricular septum following myocardial infarction: report of long asymptomatic survival. PMID- 1427955 TI - Congenital diffuse rhabdomyomatosis of the heart with biventricular outflow obstruction. PMID- 1427956 TI - Ostium primum atrial septal defect with rheumatic mitral stenosis. PMID- 1427957 TI - Protein folding: retrospective and prospective. PMID- 1427958 TI - Molecular mechanics simulation of the interaction of estrogen receptor with estrogen regulatory element. AB - A model for the interaction of 31 amino acid fragment (protein) from DNA binding domain of human estrogen receptor (hER) with a five base pair DNA sequence 5'GGTCA 3' from estrogen regulatory element (ERE) has been obtained using a step wise procedure based on structural data on model peptides, DNA binding domain of hER, steric constrains imposed by tetrahedral coordination of the Cys sulphurs with zinc ion and classical secondary structural elements. Structure of the protein as well as its complex with DNA is obtained by energy minimization followed by refinement by molecular mechanics. The complex is stabilized by H bonds between Lys22, Lys26 and Arg27 with DNA bases G2, T3 and T6. Lys22 also made H-bond with the backbone of G2. The backbone of Cys18 H-bonded with N7 of G1. DNA was in distorted B form and showed evidence of protein-induced conformational changes. PMID- 1427959 TI - Computer aided study of the interaction of thyroid hormone receptor with DNA. AB - Interaction of the first zinc finger from human thyroid hormone receptor (finger) with hexanucleotide duplex d(AGGTCA).d(TGACCT) from thyroid regulatory element has been studied by molecular mechanics simulation technique. The structure of the finger as well as its complex with DNA is optimized using constrain of tetrahedral coordination of the zinc ion to Cys sulphurs. The finger is stabilized by series of H--bonds (5 in backbone, 2 in side chains and 2 between backbone and side chains). The complex is stabilized by H-bonds between side chains of Tyr 11, His 12, Tyr 13 and Arg 14 with G2, G3 and G8. DNA is in B form. H--bonding network within DNA is preserved. Opposite strand P-P and Cl'-Cl' distances are changed slightly. There is a systematic change in the backbone torsional angles and sugar pucker. Also, there is an evidence of protein-induced conformational change in DNA. PMID- 1427960 TI - Liposomal hamycin in the control of experimental aspergillosis in mice: relative toxicity, therapeutic efficacy and tissue distribution of free and liposomal hamycin. AB - Therapeutic efficacy of liposomal Hamycin has been evaluated in an animal model system for aspergillosis in Balb/c mice. Hamycin was intercalated into soya phosphatidyl choline (SPC), SPC: choline (1:1, vol./vol.) and DMPC liposomes. A single dose of either 0.1 mg/kg, 0.25 mg/kg or 0.5 mg/kg of liposomal Hamycin and 0.1 mg/kg of free Hamycin was injected (i.v.) into animals infected with Aspergillus fumigatus. An increase in the survival rate of animals along with decrease in fungal count in various organs was observed with liposomal administration. Incorporation of cholesterol into liposomes decreased the in vivo toxicity of Hamycin in a dose dependent manner. However, antifungal activity both in the presence and absence of cholesterol showed marked variation as compared to that of non-aromatic polyenes, e.g. amphotericin B. Analysis of Hamycin distribution by HPLC in various tissues revealed higher blood concentration of this drug, when given in free form, compared to its liposomised form. These studies suggest that liposomal Hamycin is more effective than free Hamycin in controlling the experimental Aspergillosis. PMID- 1427961 TI - Human brain creatine kinase binding to immobilized cibacron blue F3GA: characterization and use in purification of the enzyme. AB - Creatine kinase (ATP: creatine N-phosphotransferase, EC 2.7.3.2) from adult human brain grey matter was purified by cibacron blue F3GA-Sepharose affinity chromatography. By gel electrophoresis of the purified enzyme under non denaturing conditions a single protein band was observed. The dye-bound enzyme was eluted using its substrate, ATP. Reversibility of the binding of purified creatine kinase to blue Sepharose by ATP in a concentration-dependent manner indicated that the cibacron blue molecule which structurally mimics nucleotides occupied the substrate binding site of the enzyme. Also the marked dependence of enzyme binding to blue Sepharose on Mg2+ concentration suggested that Mg2+ ion is capable of combining with the dye moiety to form a site-specific binding complex that is similar to the physiological substrate of creatine kinase, namely Mg(2+) ATP or Mg(2+)-ADP. PMID- 1427962 TI - Lipid composition of thylakoid membranes of cadmium treated wheat seedlings. AB - Cadmium (200 ppm) applied through the rooting medium to 30-day-old wheat plants decreased chlorophyll content, net CO2 exchanges and PSII activity by 34, 54 and 43% respectively. Thylakoid total lipids, total glycolipids, total phospholipids and total neutral lipids decreased by 22, 23, 12 and 25%, respectively, under cadmium treatment. Thylakoid membrane glycolipids had three major constituents, viz. monogalactosyl diacylglycerol, digalactosyl diacylglycerol and sulphoquinovosyl diacylglycerol. Monogalactosyl diacylglycerol and digalactosyl diacylglycerol contents decreased by 32 and 27%, respectively, under cadmium. Cadmium application also decreased the concentration of phosphatidyl glycerol and phosphatidyl choline to the extent of about 57 and 31%, respectively. On the other hand, phosphatidic acid and free fatty acids content showed an increase. These compositional changes in thylakoid membranes might be responsible for reduced PSII activity and rate of photosynthesis as observed under cadmium treatment. PMID- 1427963 TI - Studies on phospholipids of different mutants of Salmonella minnesota. AB - Lipid composition of the cells of smooth (S form) and core-defective rough mutants (Ra, Rb & Re) of Salmonella minnesota has been studied. The readily extractable lipids (RELs), acid-extractable lipids, and polar and nonpolar phospholipids have been analysed. Fatty acid composition of the different fractions containing phospholipids and other neutral lipids have been determined by GLC and GC-MS techniques. Phosphatidyl glycerol (PG), phosphatidylethanolamine (PE) and diphosphatidyl glycerol (DPG) were the major phospholipids present in all the strains. The major saturated fatty acid found was C16:0, and unsaturated fatty acids were, C16:1 and C18:1. Cyclopropane fatty acids, C17cy and C19cy, were also present in small amounts. Increased amounts of REL and unsaturated fatty acids were found in the mutants compared with the smooth strain. The amount of PG and PE decreased and DPG increased in the mutant strains. PMID- 1427964 TI - Effect of quassin on the metabolism of catecholamines in different life cycle stages of Culex quinquefasciatus. AB - Quassin, a mosquito larvicide isolated from Quassia amara, inhibits tyrosinase activity in the larvae of Culex quinquefasciatus. Since tyrosinase is directly involved in sclerotisation of the cuticle, it is suggested that quassin, as a larvicide, inhibits development of the cuticle. In presence of quassin phenylalanine, tyrosine and L-dopa levels were increased in larvae. In the larval stages, mosquitoes have a high concentration of phenylalanine and tyrosine with the level of the latter being very high just before pupation and then declines sharply. Monoamine oxidase (MAO), an enzyme directly involved in the metabolism of catecholamines, remained unaffected by quassin, in fact the level of adrenaline also remained unchanged in larvae during quassin poisoning. MAO showed high variation in its activity between synthetic and natural substrates. Tyramine is not a substrate for MAO. Tyrosinase activity was high in developing stages and negligibly low in adults and showed specificity to L-dopa. Phenylalanine and tyramine are unaffected by tyrosinase. Blood feeding did not influence the activity of both these enzymes. PMID- 1427965 TI - Restoration of antioxidants in liver by methionine feeding in experimental rat urolithiasis. AB - The effect of methionine or citrate on antioxidant defense system has been studied in urolithic rat. Liver weight and its protein concentration did not change in the rats fed with calculi producing diet (CPD) when compared to normal diet fed rats. Feeding rats along with citrate (c-CPD) or methionine (m-CPD) improved their body weight gain. Liver microsomes and mitochondria fractions of CPD and c-CPD fed groups showed increased susceptibility for lipid peroxidation in presence of ascorbate and t-butyl hydroperoxide when compared to either control or m-CPD fed groups. Increased superoxide dismutase and xanthine oxidase activities, decreased catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities, decreased concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin-E and increased formation of hydroxyl radical, hydroperoxides and diene conjugates were observed in the liver of both CPD fed group as well as c-CPD fed group. Except SOD and xanthine oxidase, all other parameters were normalized in m-CPD fed group. This suggested that feeding methionine reduced the susceptibility for lipid peroxidation by restoration of the level of free radical scavengers. PMID- 1427966 TI - Role of antibiotics in lipid peroxidation. AB - Alterations in the levels of lipid peroxides, superoxide dismutase, catalase, glutathione, free fatty acid and serum ceruloplasmin were studied in rats fed with high fat cholesterol diet administered different antibiotics, viz. ampicillin, tetracycline, streptomycin, chloramphenicol and cephalosporin. The concentrations of lipid peroxides, glutathione, free fatty acid decreased in most of the tissues, except in tetracycline, streptomycin and cephalosporin treated rats. The changes observed in the activities of superoxide dismutase and catalase in the liver and kidney of these antibiotics administered groups also are in accordance with the changes in lipid peroxides. The results show that the tetracycline is hepatotoxic and nephrotoxic, while cephalosporin and streptomycin are nephrotoxic. PMID- 1427967 TI - Effect of aspirin on isoproterenol induced myocardial infarction--a pilot study. AB - Effect of aspirin (1.2 mg/100 g body wt orally for 30 days) on myocardial infarction induced by isoproterenol (200 mg/kg body wt, subcutaneously for 2 days) has been studied in rats using activities of creatine kinase, aspartate amino transaminase, alanine amino transaminase and lactate dehydrogenase and levels of lipid peroxides as standard markers. Aspirin treatment is found to counteract the effect of isoproterenol on lipid peroxide formation and associated enzyme changes in serum and heart. PMID- 1427968 TI - Antidiabetic effect of a glycoside of pelargonidin isolated from the bark of Ficus bengalensis Linn. AB - The antidiabetic effect of a dimethoxy derivative of perlargonidin 3-O-alpha-L rhamnoside (250 mg/kg, single dose study and 100 mg/kg/day long term study) isolated from the bark of Ficus bengalensis Linn. has been compared with that of glibenclamide (2 mg/kg and 0.5 mg/kg/day respectively) in moderately diabetic rats. The single dose glycoside treatment decreased fasting blood glucose by 19% and improved glucose tolerance by 29%. The corresponding effects of glibenclamide were 25% and 66% respectively over the control values. On one-month treatment the fasting blood glucose levels went down almost to half of the pretreatment levels in both the groups and their glucose tolerance improved by 41% in glibenclamide group and by 15% in glycoside treated group. Urine sugar decreased to traces in both the groups and they appeared healthy. In vitro studies showed that insulin secretion by beta-cells was more in presence of the pelargonidin derivative than in presence of a leucocyanidin derivative, reported to be a good anti-diabetic agent. PMID- 1427969 TI - 23rd meeting of the Society of Immunology. Mainz, Germany, October 28-31, 1992. Abstract. PMID- 1427970 TI - Strain- and age-associated differences in lymphocyte phenotypes and immune responsiveness in C4-deficient and Albany strains of guinea-pigs. AB - Spleen lymphocytes from C4-deficient (C4D) and Albany strains of guinea-pigs, 1-7 days, 3-6 and 12-16 months old, genetically related to inbred strains 13 and 2 respectively, were analysed in terms of their expression of cell surface markers, allogenic and T- and B-cell mitogenic responses, and interleukin-1 (IL-1) and IL 2 production. There were strain- and age-associated differences in phenotypic expression and immune responsiveness levels. In both strains a significant shift in immunocompetence apparently occurs postnatally before 3-6 months of age, with no further significant changes noticed in animals 12-16 months old. Phenotypic changes in cell surface markers did not always correlate with functional capability of lymphoid cells. H159+ (pan T) and H155+ (CD4) lymphocyte number and levels of T-cell responsiveness (mitogenic and allogenic responses, and IL-2 production) were higher in C4D neonates compared with age-matched Albany guinea pigs or with young animals of the same strain. On the other hand, 31D2+ (B) lymphocytes in a significantly higher proportion in Albany neonates compared with similarly aged C4D, did not correlate at this age or at any other time with their proliferative response to lipopolysaccharide (LPS) or dextran sulphate (DS), two B-cell-specific mitogens. PMID- 1427971 TI - Maternal T cells of immunized pregnant mice induce immune suppression in their offspring. AB - The present study focused on the influence of maternal immunity during pregnancy on the responsiveness of the immune system(s) in offspring. Maternal immunization of pregnant mice with T-dependent foreign antigen sheep red blood cells (SRBC) induced suppression of anti-SRBC plaque-forming cell (PFC) responses in their offspring. We attempted to identify the cell species among the maternal lymphoid cells of the immunized pregnant mice that induced this suppression in their offspring, by separating the maternal cells into T cells, B cells and macrophages, or T-cell subsets, and then adoptively transferring them into other normal pregnant mice. The results demonstrated the following: first, maternal CD4+ T cells of immunized pregnant mice induced immune suppression in their offspring. Second, maternal T cells could be activated during pregnancy in the same fashion as in non-pregnant mice. The T-cell factor(s) for the immune suppression in offspring is produced not only by maternal T cells of immunized pregnant mice but also by T cells activated in non-pregnant mice. Third, cellular organization was required for maternal T cells to induce this immune suppression in their offspring. PMID- 1427972 TI - Lymphotoxin activates hepatic T cells and simultaneously induces profound thymic atrophy. AB - We have recently demonstrated that the liver may be a major site of extrathymic T cell differentiation. This hepatic pathway was shown to be activated in mice injected with heat-killed bacteria. It is conceivable that the resulting activation of macrophages or lymphocytes, and the production of cytokines may be responsible for a subsequent activation of hepatic T cells. In this context, we investigated the possibility of whether certain cytokines may activate hepatic T cells. It was demonstrated that the administration of lymphotoxin [tumour necrosis factor-beta (TNF-beta)] more than doubled the number of hepatic mononuclear cells (MNC) yielded 3-5 days after the treatment. More strikingly, such treatment induced profound thymic atrophy and resulted in a decrease of more than 95% in the number of thymocytes. Spontaneous proliferation in an in vitro culture of hepatic MNC from treated mice increased, and inversely such activity of thymocytes decreased. The increased number of hepatic MNC was mainly due to an increase in intermediate alpha beta T-cell receptor (TcR) cells, which are extrathymic T cells uniquely seen in the liver. On the other hand, the thymic atrophy was caused by the prompt apoptotic death of dull alpha beta TcR cells with double-positive (DP) CD4+ CD8+ phenotype. These results indicate that lymphotoxin may be one of the factors that activates extrathymic T cells in the liver and at the same time inhibits intrathymic T-cell differentiation. PMID- 1427973 TI - Patterns of dual lymphocyte development in co-cultures of foetal thymus and lymphohaemopoietic cells from young and old mice. AB - Patterns of lymphocyte development in the thymus were analysed, focusing on newly emigrating bone marrow (BM) and resident thymic cells. We co-cultured foetal (Day 15 of gestation) thymic explants (FT, C57BL/Ka, Thy-1.1), with BM cells from young (2-3 months) or old (24 months) syngeneic, Thy-1 congenic (C57BL/6J, Thy 1.2) mice. When the FT was severely depleted [treated with either 2 deoxyguanosine (dGua) or exposed to an irradiation dose of 20 Gy] BM-type T lymphocytes were dominant, regardless of BM donor age. When the FT was only partially depleted of its proper lymphoid cells (by exposure to 10 Gy), the lymphocytes which developed were from both BM and FT origins, yet the level of donor-type thymocytes from the young mice was higher than that of the old. Under these conditions the proportion of FT-derived double-positive CD4+ CD8+ (DP) cells was higher, and that of single-positive CD4- CD8+ cells was lower, than in the BM-derived cells, irrespective of the BM donor age. The proportions of old BM derived DP cells were lower than in the young. Co-cultures of thymus cells from young and old mice with partially depleted FT explants resulted in similar proportions of CD4/CD8 subsets from both donor and FT origins, with the exception that in the presence of old-thymus cells there was an increase in the level of FT type CD4- CD8+ cells. Patterns of T-cell differentiation in the thymus thus seem to be determined by newly emigrating cells and the resident thymocytes. PMID- 1427974 TI - Immune privilege in the anterior chamber of the eye: alloantigens and tumour specific antigens presented into the anterior chamber simultaneously induce suppression and activation of delayed hypersensitivity to the respective antigens. AB - Allografts placed into the anterior chamber of the eye enjoy prolonged and sometimes permanent survival while similar grafts are promptly rejected if transplanted to non-privileged sites. The immunological privilege of the anterior chamber is due, in large part, to the systemic suppression of delayed-type hypersensitivity (DTH) that is induced by anterior chamber presentation of alloantigens and is termed anterior chamber-associated immune deviation (ACAID). Although many categories of antigens elicit ACAID, strong tumour-specific transplantation antigens (TSTA) do not induce ACAID and instead, provoke potent DTH responses following anterior chamber presentation. The present study sought to determine if the anterior chamber were simultaneously confronted with these two categories of antigens, which systemic immune response would prevail: DTH or suppression of DTH? The results show that inoculation of minor histocompatibility alloantigens and TSTA into the anterior chamber induced both afferent and efferent suppression of specific anti-alloantigen DTH responses, yet simultaneously induced normal anti-TSTA DTH responses. Both responses (i.e. DTH and suppression) were transferable with lymphoid cells. PMID- 1427975 TI - Phenotypic and ultrastructural characterization of an epithelial cell line established from rat thymic cultures. AB - An epithelial cell line (TE-R 2.5) was established from a long-term culture of rat thymic epithelium. Its epithelial nature was confirmed using anti-cytokeratin (CK) monoclonal antibodies (mAb) and electron-microscopy. TE-R 2.5 cells were reactive with K 8.13, K 8.12, CK 8, R-MC 18, R-MC 19 and Mar 3 mAb and bind Ulex europaeus agglutinin I. Based on the results of this study it was concluded that they possess the phenotype of subcapsular/perivascular or medullary epithelium. This was in accordance with Western blot analysis of water-insoluble cell extracts showing the presence of 56,000, 52,000, 50,000 and 48,000 MW CK polypeptides. In addition, TE-R 2.5 cell line coexpressed CK and vimentin (a 57,000 MW polypeptide) which was demonstrated using dual immunohistochemistry and Western blot analysis. Electron microscopy demonstrated that TE-R 2.5 cells have all the characteristics of hypertrophic thymic epithelial cells (TEC) localized in situ exclusively in the medulla and thus further characterized this line as a type of medullary TEC. Finally, TE-4F10 mAb raised against an antigen of TE-R 2.5 cells selectively stained a subset of medullary TEC in situ including Hassall's corpuscles indicating again the medullary origin of this TEC line. PMID- 1427976 TI - Monoclonal antibodies to the murine VLA-6 alpha-chain trigger homotypic lymphocyte aggregation. AB - Very Late Antigen-6 (VLA-6) is a laminin receptor found on T cells, macrophages and platelets and may function as an activation antigen. Here we describe that two monoclonal antibodies (mAb) targeting the VLA-6 alpha-chain are capable of inducing homotypic aggregation of murine T-cell lines (3A9 and C10 cells). 3A9 and C10 cells are of the memory phenotype (CD4+, CD8-, CD44+, CD45+) and express VLA-6 abundantly. The VLA-6-induced aggregation is temperature dependent, energy requiring, and involves the cytoskeleton. In addition, divalent cations (Ca2+ and Mg2+) are also necessary for aggregation. The VLA-6-induced aggregation is not inhibited with mAb targeting the LFA-1/ICAM-1, VLA-4/VCAM-1 and CD2/LFA-3 adhesion pairs. We conclude that VLA-6 has a broader function and can serve as an activation molecule, triggering homotypic aggregation of T-cell subsets. PMID- 1427977 TI - Interleukin-1 receptor antagonist in inflammatory exudate cells of rabbits. Production, purification and determination of primary structure. AB - A rabbit interleukin-1 (IL-1) inhibitor in inflammatory peritoneal exudate cells was purified to apparent homogeneity. This inhibitor was extracted from exudate cells of the 24-hr stage of casein-induced peritoneal inflammation and purified using isoelectrofocusing (IEF), gel filtration, followed in this order by high performance liquid chromatography (HPLC) steps with hydroxylapatite and anionic ion exchanger. The purified factor showed a single band on silver-stained SDS PAGE. This molecule of MW 19,000 and pI 5.5 inhibited the binding of both IL-1 alpha and beta to receptors on a thymoma cell line, EL-4 and a B-cell line, 70Z/3. We determined its primary structure by a combination of peptide chemistry and molecular cloning. The inhibitor was synthesized as a precursor composed of 177 amino acids and was processed to a mature molecule of 143 amino acids. The N terminal amino acid of the mature inhibitor was N-acetyl-methionine residue. The deduced amino acid sequence of the inhibitor showed a 77% homology to the human IL-1 receptor antagonist (IL-1Ra) and essentially the same mode of action as seen with human IL-1Ra. We consider that this inhibitor is a rabbit counterpart of human IL-1Ra, although there are differences with respect to the molecular structure; the N-terminus of the mature rabbit IL-1Ra at a position of nine amino acids downstream from that of human IL-1Ra. PMID- 1427978 TI - Inhibition of interleukin-1 beta mRNA expression and interleukin-1 alpha and beta secretion by a specific human recombinant interleukin-1 receptor antagonist in human peripheral blood mononuclear cells. AB - The transcription and translation of interleukin-1 (IL-1) may have a pleiotropic effect on the immune system and inflammatory diseases. Recently it has been reported that human monocytes not only produce IL-1 but also induce, with adherent IgG, the secretion of an IL-1 receptor antagonist (IL-1Ra), which can play an essential in vivo and in vitro role in the regulation of IL-1 activity. Recombinant human (rh) IL-1Ra is structurally similar to IL-1 beta but with no IL 1-like activity, and specifically binds to the IL-1 receptor. To more fully evaluate and clarify the inhibitory effect of rhIL-1 receptor antagonist on IL-1 we have studied the influence of rhIL-1Ra on IL-1 transcription and translation. In this report we show that IL-1 beta mRNA from peripheral blood mononuclear cells (PBMC) is strongly inhibited (66%) when rhIL-1Ra (250 ng/ml) was added to cultured cells activated with lipopolysaccharide (LPS) (100 ng/ml) for 4 hr, determined with the slot blot analysis. The addition of exogenous rhIL-1 beta to the cell culture diminished the inhibitory effect (44%). Moreover, we report that the block of IL-1 mRNA transcription consequently leads to the inhibition of IL-1 alpha and IL-1 beta secretion in human PBMC, as measured by ELISA method. In fact, herein we show that LPS activates human PBMC to secrete IL-1 beta and IL-1 alpha, an effect inhibited, in a dose-dependent fashion by rhIL-1Ra (0.025-250 ng/ml) in an overnight incubation. Since IL-1 is a strong inducer of IL-1 synthesis in vivo and in vitro, in our study we used rh IL-1 alpha to stimulate the secretion of IL-1 beta in human PBMC. This activation, carried out overnight, also provoked the release of IL-1 beta in a dose-dependent manner, which was strongly inhibited by rhIL-1Ra used at different concentrations (0.025-250 ng/ml). The inhibitory effect exerted by IL-1Ra on human PBMC IL-1 mRNA transcription and the down-regulation of secretion of IL-1 beta stimulated by IL 1 alpha, may contribute to therapeutic effects in inflammatory diseases such as rheumatoid arthritis and other autoimmune diseases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1427979 TI - Suppression by Trypanosoma cruzi of T-cell receptor expression by activated human lymphocytes. AB - The immunosuppression that develops during Chagas' disease and African sleeping sickness is thought to facilitate survival of the causative agents in their mammalian hosts. Whereas a number of manifestations of immunosuppression manifested during the course of these diseases has been reported in patients and animals, the mechanisms by which they are induced remain obscure. An in vitro system in which phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear (PBMC) were co-cultured with purified Trypanosoma cruzi or T. brucei rhodesiense was used in the present work to establish whether these organisms were able to alter the capacity of activated helper/inducer (CD4+) or cytotoxic/suppressor (CD8+) cells to express T-cell receptor (TcR). Suppressed interleukin-2 receptor (IL-2R), known to be caused by both the trypanosomes and supernatants containing their secretion products, was the independent parameter used to demonstrate the occurrence of immunosuppression in all experiments. We found marked reductions in the percentage of TcR+ cells in T. cruzi-containing cultures as early as 18 hr after PHA stimulation. This alteration was still readily demonstrable after 72 hr of culture, i.e. when last tested for. Suppressed TcR expression occurred concomitantly with reduced levels of CD4 or CD8 molecules on the surface of helper/inducer and cytotoxic/suppressor T lymphocytes, respectively, indicating that the parasite had induced more than one alteration in the same cells. These effects were reproduced when the trypanosomes were separated from the PBMC by a 0.45 micron pore size filter or when filtrates from T. cruzi suspensions substituted for the parasite in the cultures, indicating that TcR suppression was mediated by a parasite secretion product(s). Interestingly, neither T. b. rhodesiense nor filtrates of suspensions of this organism altered significantly the level of TcR expression in cultures in which suppressed IL-2R expression by activated human T cells took place. Thus despite sharing the ability to impair IL-2R expression, T. cruzi and T.b. rhodesiense appear to differ in other mechanisms by which they affect human T-cell function. If occurring in infected hosts, the alterations that T. cruzi causes in the expression of TcR, CD4, CD8 and IL-2R--all molecules playing important roles in lymphocyte activation--could contribute to the development of the immunosuppression observed during the acute phase of Chagas' disease. PMID- 1427980 TI - Protection against Chlamydia psittaci in mice conferred by Lyt-2+ T cells. AB - A murine model was used to study the respective roles of L3T4+ and Lyt-2+ T cells in protection against Chlamydia psittaci. Donor mice were intravenously (i.v.) infected with 1 x 10(5) plaque-forming units (PFU) per mice of live C. psittaci. One month after inoculation, splenic cells from donors were transferred into syngenic recipients (5 x 10(7) cells/mouse). As measured by splenic colonization on Day 6 after i.v. challenge (1 x 10(5) PFU/mouse), transfer with primed (untreated) cells conferred a 3 log protection in this model. In vitro treatment, before transfer, of splenic cells with anti-Lyt-2 monoclonal antibody (mAb) and complement, markedly impaired the protection in comparison with control mice transferred with primed untreated cells, whereas treatment with anti-L3T4 mAb did not reduce the transferred protection. Resistance to a reinfection with C. psittaci was also studied after selective in vivo depletion of L3T4+ and Lyt-2+ T cells. One month after primary infection, mice were treated with anti-L3T4 or anti-Lyt-2 mAb and challenged thereafter (i.v., 1 x 10(5) PFU). The splenic colonization on Day 6 after challenge demonstrated that treatment with anti-Lyt-2 mAb impaired resistance against a subsequent infection with C. psittaci. Treatment with anti-L3T4 mAb in vivo had no effect on protection, as previously described in vitro. The mechanisms by which Lyt-2+ T cells could participate in the elimination of bacteria were discussed. PMID- 1427981 TI - Antigen-presenting characteristics of peritoneal cells of Salmonella enteritidis 11RX-infected mice. AB - Investigation of the possibility that infection with intracellular bacterial parasites such as Salmonellae may modulate the function of antigen-presenting cells (APC) revealed no major change in APC function of peritoneal cells (PC) harvested from the peritoneal cavity of mice 1-3 days after intraperitoneal immunization with S. enteritidis 11RX. Analysis of the phenotype of the Salmonella-primed T cells which responded when cultured with PC from either normal or infected mice and Salmonella-antigen showed that only L3T4+ T cells proliferated. This was also true when PC from normal and infected mice were compared for their ability to induce allogeneic responses; both L3T4+ and Lyt 2.2+ T cells were induced to proliferate, with the majority belonging to the class I restricted, Lyt-2.2+ phenotype. Significant levels of alloantigen specific Lyt-2.2+ cytotoxic T-cell activity were also induced in both types of cultures. However, a minor population of adherent cells which inhibited Salmonella antigen-specific T-cell proliferation in vitro was detected in peritoneal cell suspensions harvested 3 days after intraperitoneal immunization with S. enteritidis 11RX. Further characterization of these peritoneal cells revealed that they also inhibited the induction of in vitro T-cell responses to alloantigens. It is likely that the cells mediating these inhibitory effects belonged to a macrophage-like subset. PMID- 1427982 TI - Heterogeneity of human blood monocyte: two subpopulations with different sizes, phenotypes and functions. AB - Human blood mononuclear cells from normal adults were collected after density-cut centrifugation and monocytes were then isolated by removal of lymphocytes using the techniques of E-rosetting and cell adhesion. The purified monocytes were further analysed by velocity sedimentation, and two distinct subpopulations with different cell sizes were obtained. The larger monocytes were 17.0 +/- 1.8 microns in diameter with a mean sedimentation rate (SR) of 7.0 +/- 0.6 mm/hr, while the smaller monocytes were 9.5 +/- 0.8 microns in size and 4.1 +/- 0.2 mm/hr in SR. The population ratio of larger:smaller cells was approximately 2:1 (66 +/- 2.8%:34 +/- 1.6%). Both cell populations exhibited a high positive rate (> 98%) in both the non-specific esterase and the peroxidase stain. However, the larger cells had much higher phagocytic activity than the smaller ones. Furthermore, the expression of monocyte-associated antigens was also different between these two subpopulations. Thus, while most of the larger monocytes (98%) could be recognized by monoclonal antibodies MY7 and OKM1, only some (35 and 61%, respectively) of the smaller monocytes could react with those antibodies. In addition, the larger monocytes secreted a significant amount of monokines including interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF alpha) and prostaglandin E2 (PGE2) and their production increased in proportion to the level of stimulation by bacterial lipopolysaccharide (LPS), whereas the production of monokines by the smaller monocytes remained at low levels and did not respond to LPS stimulation. These results reveal the existence of phenotypic and functional heterogeneity in human blood monocytes. PMID- 1427983 TI - Retention of tissue-specific phenotype in a panel of colon carcinoma cell lines: relationship to clinical correlates. AB - A panel of eight cell lines has been derived from colon carcinomas. These cell lines have both been characterized according to standard criteria of growth rate, response to mitogens (epidermal growth factor and basic fibroblast growth factor), xenograft growth and growth in soft agar, and according to the ability of the cells to express epitopes known to be expressed by cells in the normal intestinal mucosa. The expression of epitopes present in columnar (absorptive) cells has been assessed using a panel of monoclonal antibodies to brush border peptidases and disaccharidases, villin and brush border-specific peptides. Goblet cell epitopes have been determined by monoclonal antibodies to mucin and carcinoembryonic antigen. An antibody to chromogranin was used to identify endocrine cells. Using these antibodies we found that all the cell lines reacted with at least one of the antibodies to columnar cells. Similarly, varying proportions of cells in six of the eight cell lines stained with antibodies to mucin. None of the cells expressed chromogranin. Expression of a differentiated colonic phenotype, as measured from antibody staining, did not correlate with measurements of malignancy, such as the ability of the cells to grow in soft agar or as xenografts. Similarly, there was no correlation between retention of a colonic phenotype and the initial pathological stage of the tumour from which the cell lines were derived. PMID- 1427985 TI - Parasite-induced changes to localized erythrocyte membrane deformability in Plasmodium falciparum cultures. AB - The effect of intra-erythrocyte development of the Plasmodium falciparum parasite on local deformability of human erythrocyte membranes was studied by aspiration of cells into 0.56 micron diameter pores in polycarbonate filters and examination, after fixing, with a scanning electron microscope. As the aspiration pressure increased, the erythrocyte membrane was extruded into the filter pores. The pressure dependence of the protrusion length and the minimum pressure required to produce any deformation provided measures of the membrane shear and the bending moduli, respectively. At the trophozoite and, to a greater extent, schizont stage of development, host cell membrane deformability was significantly decreased. There was no appreciable difference between uninfected and ring infected erythrocytes. PMID- 1427984 TI - Differential eicosanoid synthesis by murine fetal thymic non-lymphoid cells. AB - The temporal patterns of synthesis of prostaglandin (PG)E2 and PGI2 by organ cultured fetal thymic lobes and the cell population(s) responsible for synthesis of such products within the murine fetal thymus have been investigated. Embryonic day 14 thymic lobes were organ-cultured in defined media for 14 days and the media were collected every 24 h and replaced with fresh media. Collected media were processed for quantitation of either PGE2 or PGI2. Lobes were also cultured in 2'-deoxyguanosine (1.35 mmol/L) to produce an enriched non-lymphoid population. The per cent cyclooxygenase-positive cells within non-lymphoid cell enriched lobes as well as the capacity of such lobes to synthesize either PGE2 or PGI2 were determined and compared with that of intact thymic lobes. Results demonstrate that fetal thymic lobes, in vitro, differentially synthesize PGI2 and synthesize PGE2 at a constant rate. Moreover, lobes enriched for non-lymphoid cells contain a greater percentage of cyclooxygenase-positive cells and synthesize increased amounts of eicosanoids per 10(4) cells compared with controls. PMID- 1427986 TI - Limiting dilution analysis in leprosy. AB - Peripheral blood mononuclear cells (PBM) obtained from leprosy patients and healthy controls were cultured with Mycobacterium leprae and the control antigens, BCG and SKSD. Parallel cultures were supplemented with additional interleukin-2 (IL-2). On the basis of the level of response to M. leprae, leprosy patients could be divided into low, intermediate and high responders. The addition of IL-2 resulted in enhanced proliferation to antigen only by cells from intermediate responders. This effect was neither antigen specific nor was it confined to cells from leprosy patients. When limiting dilution analyses were performed on cells from 26 patients across the leprosy spectrum, no M. leprae reactive lymphocytes were detected in cells from subjects with lepromatous disease. The precursor frequency for cultures containing M. leprae plus IL-2 was no greater than that of cultures containing IL-2 alone, thereby excluding the possibility of clonal anergy reversible with IL-2. This was observed in both untreated patients and those on long-term treatment, which made sequestration of antigen-reactive cells within leprosy lesions an unlikely explanation. On the other hand, M. leprae-reactive lymphocytes were detected in patients with tuberculoid and borderline tuberculoid disease and in two subjects with borderline lepromatous leprosy in type I reversal reaction. IL-2 reactive cells were detected in all patients regardless of clinical classification. Three 'suppressor' curves were obtained but were not confined to cells from lepromatous patients. Taken together, these findings suggest that the non-responsiveness to M. leprae characteristic of the great majority of multibacillary patients is due to an absence of antigen-sensitive T cells. PMID- 1427987 TI - D11, a novel monoclonal antibody specific for human mature macrophages and peripheral blood monocytes. AB - A new monoclonal antibody designated Mab D11 is described, which shows a restricted reactivity to cells of the monocyte/macrophage system. When tested by light and electron microscopic immunoperoxidase methods, Mab D11 specifically reacts with blood monocytes and stains resident macrophages in a wide variety of human tissues; it does not mark the macrophages of other species, i.e., rat, swine and mouse. Antigen-presenting cells, e.g., Langerhans cells, are Mab D11 negative. Mab D11 reveals the antigen on cryostat and paraffin tissue sections. Ultrastructurally the antigen recognized by Mab D11 in all macrophage types studied is located on the plasma membrane and within cytoplasmic structures including lysosomes. On immunoblotting, Mab D11 detects the 125-kDa antigen in human liver and the 135-kDa protein in tumours of histiocytic origin. The similarity of Mab D11 to known "pan-macrophage" monoclonal antibodies is discussed. PMID- 1427988 TI - Interferon-gamma is unable to increase monocyte and neutrophil-mediated nonspecific cytotoxicity induced by immune complexes. AB - We have previously demonstrated that normal human neutrophils and monocytes triggered by immune complexes (IC) are able to destroy non-sensitized target cells through the activation of a nonspecific cytotoxic mechanism (NSC), that is dependent on the generation of reactive oxygen intermediates (IRO). In the present study, we analyze the ability of interferon-gamma (IFN-gamma) to modulate NSC. Our results indicate that, despite the ability of IFN-gamma to increase both the generation of superoxide anion and hydrogen peroxide by phagocytic cells and the expression of the high-affinity 72-kDa Fc gamma RI, it is completely unable to increase NSC mediated either by neutrophils or monocytes. These data suggest that there is no correlation between cytotoxicity and the ability of phagocytic cells to release superoxide anion and/or hydrogen peroxide. They also indicate that Fc gamma RI is not involved in the induction of NSC. To further analyze this point, we studied the ability of two monoclonal antibodies (mAb), specific for different epitopes of Fc gamma RI, to inhibit NSC. These mAb strongly inhibited ADCC mediated by untreated monocytes or IFN-gamma treated monocytes and neutrophils. On the other hand, they were completely unable to inhibit NSC mediated by untreated or IFN-gamma treated cells. PMID- 1427989 TI - Identification of C-terminal peptides of bovine beta-casein that enhance proliferation of rat lymphocytes. AB - A casein polypeptidic fraction, obtained from a pepsin-chymosin digestion of caseins, showed a mitogenic effect on primed lymph node (LN) cells and unprimed spleen cells of rats. A biologically active C-terminal sequence of bovine beta casein (residues 192-209) was characterized. The corresponding synthetic peptide had a stimulatory effect on primed LN cells but failed to enhance proliferation of spleen cells. We prepared two chymosin digests (PA and PB) of bovine beta casein which contained, respectively, 80% and 95% of the sequence including residues 193-209. They induced a significant proliferative response in both LN and spleen cells. It is therefore possible that other active peptides in the PA preparation may be involved in mitogenic activity. PMID- 1427990 TI - Deficient transformation of murine trisomy 16 fetal liver cells by the Abelson and J2 viruses. AB - Mouse trisomy 16 (Ts16), an animal model for human Down syndrome (trisomy 21), exhibits severe abnormalities in the development of lymphoid and myeloid cells. Whereas fetal liver cells from diploid mice can be easily immortalized by retroviral transformation with Ab1-MuLV or J2 virus, fetal livers from Ts16 mice contain significantly fewer transformable cells. Infection of Ts16 fetal liver cells by Ab1-MuLV results in a 52- and 12-fold reduction in the frequency of transformation at days 17 and 18 of gestation, respectively. By contrast, the efficiency of transformation with J2 virus, another retrovirus known to transform fetal liver cells, is only mildly (factor 2-3) affected. The Ig gene rearrangements of Ts16 and diploid retrovirally transformed fetal liver cell lines do not differ from one another. This suggests that there is a deficiency in the early stem cell compartment, rather than in the development of pre-B cells. PMID- 1427991 TI - Rabbit single domain antibodies specific to protein C expressed in prokaryotes. AB - VDJ genes were amplified by the polymerase chain reaction from mRNA isolated from peripheral blood B cells of rabbits immunized with protein C. The amplified genes were cloned into a lambda phage expression vector and packaged. A library of 6 x 10(5) recombinant phages was screened with labelled protein C and 30 positive clones were found. Three of them were plaque purified and the affinity of the single domain antibodies to the antigen determined to be 10(6)-10(7) l M-1. The data indicate the feasibility of generating single domain antibody, specific to protein antigen, from rabbit. PMID- 1427992 TI - Immunosuppression induced by hepatic portal venous immunization spares reactivity in IL-4 producing T lymphocytes. AB - Immunization of naive or specifically primed C3H/HEJ with irradiated B10.BR spleen cells via the hepatic portal vein leads to an antigen specific decrease in the proliferative and cytotoxic response to B10.BR antigen assayed in vitro (and to increased graft survival of B10.BR grafts in vivo). This effect seems to be mediated in the main by a decrease in IL-2 production from CD4+ T lymphocytes of mice given antigen by the portal route, which is in turn caused by a decreased precursor frequency of IL-2-producing cells. No clear decrease in IL-4 production was seen. Hepatic APC isolated from mice receiving antigen via the portal vein were unable to induce IL-2 production from a C3H/HEJ anti-B10.BR cell line in vitro, in contrast to splenic APC derived from the same mice. Even when antigen was given by conventional (systemic) intravenous routes (in this case via the lateral tail vein) hepatic APC isolated from those mice were unable to stimulate IL-2 production from this cell line. Furthermore, 24 h exposure of a cell line to antigen pulsed hepatic APC left those cells refractory to a subsequent restimulation with antigen presented by splenic APC. Spleen lymphoid cells from primed mice challenged in vivo with B10.BR liver cells (i.v.) were similarly unable to produce IL-2 on rechallenge in vitro with irradiated B10.BR spleen cells, though no defect was seen if in vivo challenge was with B10.BR spleen cells. These data imply that presentation of multiple minor cell surface antigens by hepatic APC leads to specific anergization of IL-2 producing T cells, in a fashion which seems to be distinct from that previously reported as due to 'veto like' activity. PMID- 1427993 TI - Perforin gene expression in stimulated human peripheral blood T cells studied by in situ hybridization and northern blotting analysis. AB - In situ hybridization was used here to monitor the mRNA level of the pore-forming protein perforin in mitogen-stimulated primary peripheral blood human T cells. In situ hybridization was performed using sense and antisense ribonucleotide probes specific for this granule mediator. After IL-2 treatment, an increase in perforin mRNA could be detected by 4 h; they peaked at 12 h, and decreased after 24 h. The perforin mRNA was also induced in T cells treated with a combination of phorbol ester PMA plus lectin or OKT3 mAb. This latter induction followed slower kinetics, peaking at 48 h. For all three mitogens used, even at peak induction times less than 10% of T cells were labeled with perforin probe. Similar patterns of mRNA expression were observed for both unprimed T cells and lectin-primed T blasts. The induction response of mRNA due to IL-2 stimulation is probably mediated by the IL-2 receptor p75 chain since its mRNA was upregulated by IL-2 with a kinetics comparable to that associated with an increase of perforin mRNA. The p55 IL-2 receptor chain increased much more slowly than p75. PMID- 1427994 TI - Effect of beta 2-microglobulin on immunoglobulin production. AB - Chronic renal failure patients display high serum levels of beta 2-microglobulin (beta 2-M) and a pronounced defect in immunoglobulin production. In this light, the present study was conducted to investigate whether beta 2-M might influence the rate of antibody synthesis. Peripheral blood mononuclear cells (PBMC) from healthy subjects were cultured in the presence of beta 2-M (80 mg/l) for 7 days. Immunoglobulin concentrations were measured by ELISA-techniques in culture supernatants. Basal IgM levels were 390 +/- 10 ng/ml and increased to 940 +/- 216 ng/ml in the presence of beta 2-M. After PWM stimulation, IgM concentrations were 2654 +/- 614 ng/ml without and 3750 +/- 914 ng/ml with beta 2-M. IgG and IgA production by PBMCs was not influenced by beta 2-M in the culture medium. Likewise, the generation of beta 2-M by PBMCs was unchanged in the presence of exogenous beta 2-M in the medium. In terms of clinical relevance, serum beta 2-M levels of 28 uremic patients were correlated with capacity of their PBMCs for immunoglobulin production in vitro. However, there was no apparent correlation between beta 2-M serum levels and immunoglobulin synthesis in vitro. Taken together, beta 2-M seems to have a stimulatory effect on IgM synthesis in vitro. Whether this has some clinical meaning in patients with chronic renal failure remains to be investigated. PMID- 1427995 TI - Anti-leukocyte antibodies as a consequence of HIV infection in HIV+ individuals. AB - Antibodies (Ab) that induce antibody-dependent cell-mediated cytotoxicity (ADCC) against non-T lymphocytes, anti-HLA class II specific Ab and anti-PMN were tested in hemophilic (He) patients who were alloimmunized because they had received replacement treatment with blood derivates and become infected with HIV, as well as in those who remained seronegative. In addition, the serum reactivity of spouses of HIV+ individuals and their children was studied to determine the effect of HIV infection in the absence of concomitant alloimmunization. The results of this study indicate that ADCC Ab were already present in HIV- He, suggesting the influence of alloimmunization. Their titer increased after appearance of HIV disease. While low reactivity against class II antigens was observed in HIV- He, activity augmented sharply after HIV infection and increased further with disease progression. Anti-PMN reactivity followed a similar pattern. Anti-class II, ADCC Ab and anti-PMN were also detected in the asymptomatic HIV+ spouses of HIV+ patients in titers that were similar to those of asymptomatic HIV+ He. In children born to HIV+ mothers in whom HIV infection was confirmed, anti-class II, ADCC Ab and anti-PMN reactivity were also observed, and activity increased after the onset of disease. These results suggest that induction of anti-leukocyte Ab occurs in the absence of massive allostimulation after HIV infection. HIV infection may enhance preexisting class II and anti-leukocyte response in allostimulated individuals. PMID- 1427996 TI - Extracellular diaphorase-like activity as a marker of cytolytic damage to cells. AB - A new variant of the enzyme release colorimetric method for NK/LAK cytotoxicity is described. Kinetic determination of diaphorase released from damaged target cells (TC) provided an exact measurement of the lytic activity of effector cells (EC). A polyenzyme testing system permitted the use of a wide spectrum of TC. The percentage cytotoxicity and the kinetics of the process coincide, within experimental error, with data from staining with Trypan blue. The method is simple and convenient and can be applied to study cell-mediated cytotoxicity (CMC). PMID- 1427997 TI - H2 genotype and IgE immune response to Fel dI, the cat major allergen, in mice. AB - Mice of 6 strains were immunized with a highly purified Fel dI allergen adsorbed to alum. Their ability to display a significant IgE response was detected via passive cutaneous anaphylaxis (PCA) tests, performed in rats. Linkage of the responsiveness to the H2 genotype is not totally obvious. IgE response can be delayed, particularly in the SJL strain (H2-s histocompatibility allele), and lacking in the C57 B1/6 strain (H2-b). Mice with H2-k, H2-d alleles and the B6D2F1 hybrid H2-b/d are good responders, leading to the hypothesis that the IgE response to Fel dI may be related to the H2-d allele. For all good responders, individual variations are rather important. All our observations show that mice perfectly mimic human hypersensitization to the cat major allergen Fel dI, at least where the IgE response is concerned. PMID- 1427998 TI - In vitro bioassay for type E prostaglandins based on their NK immunodepressing activity. AB - A biological assay for PGE in commercial preparations, or secreted by tumor cells in culture fluid was developed on the basis of the immunosuppressive effect of PGE on the cytotoxic activity of NK cells. The assay is simple, rapid and convenient for detecting PGE cell secretion, either spontaneous or induced by various signals. The sensitivity of the bioassay is limited by the sensitivity of NK cells to the immunosuppressive activity of PGE (i.e., about 10(-8) M). PMID- 1427999 TI - Radioresistant cells of thymus--producers and targets of thymocyte growth factor and their possible role in postradiation restoration of thymus. AB - In the present study the association between the damaging and the stimulating action of radiation on the cells of thymus (in particular intrathymic T lymphocyte precursors, TLP) is analyzed. The radioresistance and possibility to secrete humoral products, in particular, the thymocytes growth factor, THGF, is assessed. The possible role of THGF in the postradiation restoration of thymus is also discussed. PMID- 1428000 TI - Down-regulation of murine B lymphocyte growth: arrest of B cells in G1 underlies immunosuppression induced by an IgM antibody. AB - Previous studies have demonstrated that culture supernatants of LPS-stimulated murine splenic B lymphocytes (BLPSSN) are able to inhibit the growth of freshly isolated B cells via an IgM antibody. In this work we investigated the progress of LPS-activated B lymphocytes through the cell cycle in the presence of this antibody. We found that the regulatory IgM did not affect the entry of LPS stimulated B lymphocytes into G0*, as assessed by the increased expression of I-A antigens. Events that characterize the early G1 phase (G1A), such as cell enlargement and increased RNA synthesis, also occurred in the presence of the antibody. In contrast, events which mark the G1B phase, such as further cell enlargement and late RNA synthesis were inhibited. Moreover, a significant portion of the cells failed to incorporate [3H]thymidine and did not progress through S, G2, or M, as revealed by their DNA content. Therefore, our work points toward a well-defined stage of the early G1 phase at which the antibody inhibits the progression of B lymphocyte activation. This result shows a new insight into the mechanism of antibody-mediated down-regulation of polyclonal B cell responses. PMID- 1428001 TI - Analysis of clonality of tumour infiltrating lymphocytes in breast cancer and uveal melanoma. AB - Fresh tumour infiltrating lymphocytes (TILs) from 6 uveal melanomas and 4 breast cancers were analysed by flow cytometry with a panel of 6 monoclonal antibodies to V beta regions of the T cell receptor (V betas 5a, 5b, 5c, 6, 8a and 12a). With a single exception where one TIL sample lacked V beta 12a, lymphocytes from both tumour and blood contained cells reactive with all 6 probes, and no probe was highly dominant or missing. The proportions of reactive cells differed between tumour and blood within each patient. The data indicate that while tumour infiltrating lymphocytes have a capacity to locate selectively within the tumour they nonetheless comprise a population expressing a diversity of TCR V beta genes. PMID- 1428002 TI - Skin response to tuberculin in pig foetuses and germ-free piglets. AB - Cellular response to intradermally administered PPD (2 TU) was demonstrated in pig foetuses of various ages and in germ-free piglets. CD2+, CD4+, CD8-, 86D-, SLA-D- T lymphocytes were the predominant cells in the skin tuberculin reaction in both foetuses and germ-free animals. Reactive T cells were observed as early as in mid-gestation, whereas SLA-D+ (porcine MHC class II) cells appeared only in older foetuses. Polymorphonuclear leukocytes were never observed in the PPD reaction. PMID- 1428003 TI - Sequence and chromosome assignment to 11p13-p12 of human RAG genes. AB - The recombination-activating genes RAG-1 and RAG-2 are required for V(D)J DNA rearrangements at loci for immunoglobulin and T cell receptor genes. We isolated the human RAG-2 gene and determined its nucleotide sequence. Mapping analysis of RAG-1 and RAG-2 genes on human chromosomes by fluorescence in situ hybridization indicated that the genes are located on chromosome 11p13-p12. RAG-1 and RAG-2 do not seem to be linked to any of the primary immunodeficiencies for which defective genes have already been mapped. PMID- 1428004 TI - A fluorescent molecular rotor probes the kinetic process of degranulation of mast cells. AB - A confocal fluorescence microscope was used to study the exocytotic secretory processes of mast cells in combination with an fluorescent molecular rotor, 9 (dicyanovinyl)julolidine (DCVJ). DCVJ is known to be an unique fluorescent dye which increases its quantum yield with decreasing intramolecular rotation. Here, DCVJ-loaded peritoneal rat mast cells were stimulated with compound 48/80 and their fluorescence images were compared with fluorescence calcium images of fluo 3-loaded mast cells. Subsequent to transient increases in intracellular free calcium ion concentration, DCVJ fluorescence increased dramatically in the cytoplasm and formed a ring-like structure around the nucleus, suggesting the possibility that the dye bound to the proteins composing the cytoskeletal architecture. Furthermore, the increases of DCVJ fluorescence intensities were mostly blocked in the presence of cytochalasin D (10 microM). However, fluo-3 fluorescence intensities still increased after addition of compound 48/80. PMID- 1428006 TI - Anti-TCR-V beta 6 breaks tolerance in female AKR, Mlsa mice inducing foetal lethality. AB - Immunisation with anti-TCR-V beta 6 of female AKR mice prior to and during syngeneic pregnancy resulted in neonatal lethality and eventually in abortion or foetal resorption. The sera of the hyperimmunised mothers were shown to have anti H-2k and anti-Mlsa autoantibodies and were cytotoxic to H-2k targets in vitro and also blocked Mlsa-induced mixed lymphocyte reactions. These observations are discussed herein. PMID- 1428005 TI - A monoclonal antibody directed against the sporozoite stage of Plasmodium vivax binds to liver parenchymal cells. AB - The circumsporozoite (CS) protein of malaria parasites is a major surface protein of the sporozoite stage. In the process of investigating the immunogenicity of this protein in the Plasmodium vivax complex, we found that a monoclonal antibody (mAb) directed against the CS protein of isolates of P. vivax recognizes New World monkey hepatocytes and human hepatoma cells HepG2A16 in Western blot and by immunoelectron microscopy. The mAb NVS3 binds to the amino acid sequence AGDR, which is also shared with the alpha 3 domain of the human and primate major histocompatibility complex class I. In addition, in vitro experiments suggest that the binding of the mAb NVS3 to hepatocytes from Saimiri monkey enhances the invasion or development of malaria sporozoites. These results form the basis for investigating the relationships between parasite surface proteins and host-cell receptors. PMID- 1428007 TI - Mhc-DRB diversity of the chimpanzee (Pan troglodytes). AB - Fifty-four chimpanzee Patr-DRB and five human HLA-DRB second exons were cloned and sequenced from thirty-five chimpanzees and four human B-cell lines and compared with known Mhc-DRB sequences of these two species. Equivalents of the HLA-DRB1*02, -DRB1*03, -DRB1*07 allelic lineages and the HLA-DRB3, -DRB4, -DRB5, DRB6, and -DRB7 loci were all found in the chimpanzee. In addition, two chimpanzee Patr-DRB lineages (Patr-DRBX and -DRBY) were found for which no human counterparts have been described. None of the Patr-DRB sequences is identical to known HLA-DRB sequences. The Patr-DRB1*0702 and HLA-DRB1*0701 alleles are the most similar sequences in a comparison between the two species and differ by only two nucleotides out of 246 sequenced. Equivalents of the HLA-DRB1*01, -DRB1*04, and -DRB1*09 alleles were not found in our sample of chimpanzees. A per locus comparison of the number of Patr-DRB alleles with the HLA-DRB alleles shows that the Patr-DRB3, -DRB4, -DRB5, and -DRB6 locus are, thus far, more polymorphic than their human homologs. The polymorphism of the Patr-DRB1 locus seems to be less extensive than that reported for the HLA-DRB1 locus. Nevertheless, the Patr-DRB1 locus seems to be the most polymorphic of the Patr-DRB loci. Phylogenetic analyses indicate that the HLA-DRB1*09 allele may have originated from a recombination between a Mhc-DRB5 allele and the DRB1 allele of a Mhc-DR7 haplotype. Although recombination seems to increase the diversity of the Patr-DRB alleles, its contribution to the generation of Patr-DRB variation is probably low. Hence, most Patr-DRB diversity presumably accumulated via recurrent point mutations. Finally, two distinct Patr-DRB haplotypes are deduced, one of which (the chimpanzee equivalent of the HLA-DR7 haplotype) is probably older than 6-8 million years. PMID- 1428008 TI - Trans-species origin of Mhc-DRB polymorphism in the chimpanzee. AB - Trans-specific evolution of allelic polymorphism at the major histocompatibility complex loci has been demonstrated in a number of species. Estimating the substitution rates and the age of trans-specifically evolving alleles requires detailed information about the alleles in related species. We provide such information for the chimpanzee DRB genes. DNA fragments encompassing exon 2 were amplified in vitro from genomic DNA of ten chimpanzees. The nucleotide sequences were determined and their relationship to the human DRB alleles was evaluated. The alleles were classified according to their position in dendrograms and the presence of lineage-specific motifs. Twenty alleles were found at the expressed loci Patr-DRB1, -DRB3, -DRB4, -DRB5, and at the pseudogenes Patr-DRB6, -DRB7; of these, 13 are new alleles. Two other chimpanzee sequences were classified as members of a new lineage tentatively designated DRBX. Chimpanzee counterparts of HLA-DRB1*01 and *04 were not detected. The number of alleles found at individual loci indicates asymmetrical distribution of polymorphism between humans and chimpanzees. Estimations of intra-lineage divergence times suggest that the lineages are more than 30 million years old. Predictions of major chimpanzee DRB haplotypes are made. PMID- 1428009 TI - Evolution of the major histocompatibility complex: a hundred-fold amplification of MHC class I genes in the African pigmy mouse Nannomys setulosus. AB - The genome of the African murine rodent Nannomys setulosus was found to harbor several thousand major histocompatibility complex (MHC) class I genes instead of the 30-40 genes found in conventional laboratory mice, which are mostly of Mus musculus domesticus origin. Other genes of N. setulosus, either functionally or physically linked to class I genes, are not amplified. Amplified genes derive from as few as three ancestors and amplification has likely occurred after the divergence of the two Nannomys species, N. setulosus and N. minutoides, which took place about three million years ago. Amplified genes are mostly pseudogenes. Statistical analysis of dinucleotide frequencies leads us to propose that inactivation of the genes has occurred through the repeat induced mutation process, a possible "newcomer" in the evolution of the MHC. PMID- 1428010 TI - Transcription and diversity of immunoglobulin lambda chain variable genes in the rat. AB - In order to determine the extent of the repertoire of the immunoglobulin light chain V-region locus (Igl-V) in the laboratory rat (Rattus norvegicus), we constructed a specifically primed cDNA library from lipopolysaccharide-stimulated DA strain rat spleens. The library was screened with a rat Igl-C2-specific probe, and 33 clones containing identifiable V regions were sequenced, of which 19 sequences are presented here. In addition to one sequence (Igl-V1) which was already known, and is closely related to the two known mouse V lambda gene segments, clones encoding representatives of three new, distantly related, rat Igl-V subfamilies were found, namely Igl-V2, Igl-V3, and Igl-V4. At least two of these sub-families, Igl-V2 and Igl-V3, contain multiple members as well as restriction fragment length polymorphism variants, indicating the presence of at least 10-15 Igl-V gene segments (including some pseudogenes) in the rat genome. An additional ten clones contained no rearranged V region, although they showed a correct J-C splice, suggesting the presence of cryptic transcriptional promoters between J lambda and the 3'-most Igl-V gene segment. Phylogenetic tree reconstruction based on amino acid sequence alignments showed at least three of the four rat Igl-V sequences clustering with distinct human Igl-V genes. Thus, although rats express lambda-bearing Ig at levels no higher than mice, the rat Igl-V locus is considerably more complex than that of laboratory mice, and its diversity reflects the products of gene duplications which predate the time of primate/rodent divergence. PMID- 1428011 TI - Transmembrane and cytoplasmic domain sequences demonstrate at least two expressed bovine MHC class I loci. AB - We have used the polymerase chain reaction to amplify cDNA from expressed bovine major histocompatibility complex class I genes. Sequences obtained from transmembrane and cytoplasmic domains were used to identify the number of expressed alleles. Data from three animals suggest that there are four major expressed alleles, representing the products of two (or more) loci. We have also demonstrated the presence of an alternatively spliced mRNA, which has been observed in five animals. The alternative splicing removes exon 7 (the major site of class I phosphorylation), which predicts a truncated molecule with a cytoplasmic portion 16 amino acids shorter than usual. This phenomenon was detected for only a single class I allele within each individual. PMID- 1428012 TI - Two subtypes of HLA-B51 differing by substitution at position 171 of the alpha 2 helix. AB - Newly defined antigens of the B5, B35 cross-reacting group have been found in Japanese and North American Indians. Nucleotide sequencing of the alleles encoding the Japanese B5.35 antigen and the variant B5 antigen from the Piman Indians show them to be identical. This new allele, B*5102, differs from B*5101 by a single nucleotide substitution that changes residue 171 from histidine to tyrosine. Residue 171, which is part of the alpha 2 helix, is believed to contribute directly to peptide interaction in the A pocket of the binding groove and is either histidine or tyrosine in all HLA-A, B, C heavy chains. Tyrosine 171 is shared by B*5102, B*3501, B*3502, and B*5301 and must be responsible for the serological cross-reactivities of these molecules not shared with B*5101. Stimulation of lymphocytes from a B*5101 positive donor with B*5102 positive cells failed to generate cytotoxic T cells with specificity for the difference between these molecules. However, one out of five clones of cytotoxic T cells raised against B*5101 failed to lyse targets expressing B*5102. Substitution of histidine for tyrosine at residue 171 affected recognition of HLA-B35-restricted human minor histocompatibility antigen-specific T cell clones. PMID- 1428013 TI - Development of persistent lymphocytosis in cattle is closely associated with DRB2. PMID- 1428014 TI - Genetic structure of the novel low-frequency haplotype HLA-B49, SC01, DR4 and its contribution to insulin-dependent diabetes susceptibility. PMID- 1428016 TI - Schistosomiasis: an overview. PMID- 1428017 TI - Human immunity to Schistosoma mansoni: observations on mechanisms, and implications for control. AB - This review summarizes the personal experiences of the authors and their colleagues during ten years of field and laboratory studies on human immunity to Schistosoma mansoni infections. There is evidence for the very slow development with age of an acquired resistance to reinfection (demonstrable after chemotherapy of the primary infection) distinguishable from a lack of reinfection due to reduced exposure. The implications of this immunity for the design of chemotherapy programs targeted at infected schoolchildren are discussed. Observational studies on the mechanisms of immunity have demonstrated a marked helminthocidal capacity of eosinophils. Subsequent correlative studies have indicated a role of IgM and IgG2 "blocking" antibodies in maintaining the continued susceptibility of young children, and of IgE antibodies in mediating protection in older individuals. Some problems in studying human immunity, and the implications for vaccine development, are also discussed. PMID- 1428015 TI - Polymorphic specificity of Q1/28, a monoclonal antibody that preferentially reacts with free class I heavy chains. PMID- 1428018 TI - Schistosomiasis: from effector and regulation mechanisms in rodents to vaccine strategies in humans. PMID- 1428019 TI - Environmental, genetic and immunological factors in human resistance to Schistosoma mansoni. AB - The design of programs for the control of endemies requires the knowledge of the principal factors that determine parasite transmission and infection levels in exposed populations. In the studies summarized in this article, the role of environmental and host specific factors in the infection by S. mansoni have been evaluated. It is shown that a limited number of factors actually influences infection intensity: water contacts, age, and sex were shown to account for 20 to 25% of infection variance, while 35 to 40% of it was accounted for by the effect of a major codominant gene. A remarkable fact is the important weighting (around 55% of the variance) of factors (the major gene and age) that influence human capacities of resistance. This observation strongly supports control measures aimed at increasing human resistance, such as vaccination. The effect of age on the development of resistance has now been observed in several studies on S. mansoni or S. haematobium. It is, therefore, a constant finding in schistosomiasis infections that resistance develops extremely slowly requiring a long period of exposure to the parasite and repeated infections. These studies provide strong incentives to increase efforts in the evaluation of the immune response of subjects living in endemic areas. Such evaluations are necessary to define vaccine and vaccination programs, and they are also urgently needed to evaluate the effects of chemotherapy on the development of immunity in children and adolescents, as well as on the persistence of protective immunity in adults. Immunological studies begin to provide a clearer picture of the role of acquired immunity in human protection against S. mansoni. It is increasingly clear that the slow development of resistance in children, as well as its alteration in certain age groups, are related to the maturation of parasite specific immunity and its alteration by specific immune factors. Thus, the development of resistance is associated with the maturation of IgE-dependent immunity, whereas blocking Ab may interfere in children and adolescents with the expression of full resistance. This finding raises the question as to whether a vaccine could include major allergens without triggering the well-known deleterious side effects associated with hypersensitivity reactions. The absence of such reactions in subjects with high parasite-specific IgE levels who are exposed to daily infections suggests that this may be feasible. PMID- 1428020 TI - The pathogenesis of granulomatous inflammation and organ injury in schistosomiasis: interactions between the schistosome ova and the host. PMID- 1428021 TI - Experimental models of immunization against schistosomes: lessons for vaccine development. AB - Schistosomiasis is a debilitating, and sometimes deadly, parasitic infection that afflicts hundreds of millions of people living in developing countries. One of the best hopes for control of this disease is vaccine development. Studies on experimental models of attenuated vaccines have proven that high levels of protective immunity can be achieved. In these systems, resistance has been shown to be directed against the migrating larval stages of the parasite and to have both cellular and humoral components. Several candidate vaccine immunogens have been identified on the basis of antibody reactivity. However, the level of protection induced by immunization with nonliving vaccines has at yet not approached the level observed with attenuated infection. Current challenges to vaccine development include identification of protective T cell immunogens, determination of ways to strengthen the immunogenicity of isolated parasite antigens, and development of methodologies to selectively stimulate protective, as opposed to ineffective or even detrimental, immune responses. PMID- 1428022 TI - Linkage between monokine production and regulation of the negative surface charge density of human monocytes. AB - The regulation of the negative surface charge density of human monocytes was investigated with the help of the synthetic glycolipid analogue BAY R 1005. This compound is incorporated into the outer membrane of isolated monocytes during 24 hours of incubation. After this time the electrophoretic mobility (EM) of monocytes is unchanged at 0.95 x 10(-4) (cm2 V-1 s-1) and remains unchanged even under conditions where non-treated monocytes increase their EM up to 1.1 x 10(-4) (cm2 V-1 s-1). In addition BAY R 1005 stops differentiation of monocytes to macrophages, it triggers monokine production and abolishes monocyte suppressor activity and spreading capability. The results show that BAY R 1005 affects intracellular features. In connection with earlier investigations of the regulation of the negative surface charge density of human monocytes (1,2) the study suggests that monokine production and maintenance of the EM of monocytes are linked. PMID- 1428023 TI - Surface matrix binding alters murine peritoneal mononuclear phagocyte TNF-alpha and IL-6 induction. AB - Interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS) are important promotors of mononuclear phagocyte (MO) activation. Signals derived from binding to a surface matrix also participate in promoting the activation process of MO. In this study, we examined the relative contribution of adherence in augmenting murine MO activation for cytokine production. Kinetic studies compared the production and secretion of tumor necrosis factor-alpha (TNF) and interleukin-6 (IL-6) by MO cultured as adherent monolayers to those of MO cultured as suspended cells in teflon vessels. All cells were maximally stimulated in vitro with IFN gamma and LPS prior to analysis. Immunoprecipitation analysis of protein and RNA slot blots showed that both secreted protein and mRNA representing TNF and IL-6 are delayed two to six hours in nonadherent MO cultures compared to adherent MO cultures. Moreover, data from bioassays confirmed that these cytokines were completely functional in both systems examined. Although IFN-gamma/LPS were able to stimulate production and secretion of TNF and IL-6 in the nonadherent cells, without cell-matrix interaction, the process was significantly delayed. These data support the hypothesis that the physical event of adherence significantly facilitates the production of specific cytokines by activated MO. PMID- 1428024 TI - A flow microsphere inhibition immunoassay (FMII) for detecting paratope binding anti-idiotypic antibodies. AB - A simple, rapid and reproducible flow microsphere inhibition immunoassay (FMII) has been developed to detect the ability of paratope specific anti-idiotypic antibody (anti-Id or AB2) to inhibit antigen binding to the corresponding paratope of the Id (AB1). To evaluate the FMII as a measurement of paratope binding anti-Id, an avian model was used to produce Id and anti-Id antibodies for the study. Both antibody to bovine serum albumin (BSA Id) and anti-BSA Id were produced in white leghorn chickens and affinity isolated from egg yolks. The anti BSA Id samples were incubated with BSA Id coated microspheres, then without rinsing, fluoresceinated BSA (BSA-FITC) was added for a short incubation period and the resulting decrease in fluorescent intensity was used to calculate the extent of inhibition. For validation, statistical comparisons of the line equations generated by BSA dilution curves and anti-BSA Id dilution curves were performed. Replications within each ligand were not significantly different which indicated the assay was reproducible for determining the presence of paratope reactive anti-BSA Id used in this model. PMID- 1428025 TI - A simple and inexpensive glucose oxidase substrate system for enzyme immunoassay. AB - A simple and inexpensive glucose oxidase substrate system was developed for enzyme immunoassay. This system is based on the formation of a coloured complex between polyvinyl alcohol or starch and iodine produced from iodide in the presence of hydrogen peroxide generated by the glucose oxidase reaction. The rate of iodine production was enhanced by the supplementation of molybdate. In an enzyme immunoassay for anti-Salmonella antibodies using glucose oxidase as the indicator enzyme, the molybdate-enhanced polyvinyl alcohol- and starch-glucose iodide substrate systems were as sensitive as a conventional glucose oxidase assay system employing horseradish peroxidase as a secondary enzyme and a suitable hydrogen-donating chromogen. PMID- 1428026 TI - The detection of a novel neutrophil-activating peptide (ENA-78) using a sensitive ELISA. AB - Neutrophil elicitation into tissue is an essential element of the host defense in response to various stimuli, including, tissue injury, infection, or cancer. This event has gained renewed interest with the discovery of a family of small polypeptides (less than 10 kD). The salient features of these cytokines are the presence of four cysteine amino acids (first two separated by one amino acid; C-X C) and their ability to induce neutrophil chemotaxis and activation. Recently, our laboratories have discovered a new member of this C-X-C chemotactic cytokine supergene family, neutrophil-activating peptide, ENA-78. ENA-78 shares significant amino acid sequence homology with neutrophil activating peptide-2 (NAP-2; 53%), growth regulated oncogene/melanoma growth stimulatory activity (GRO alpha; 52%), and IL-8 (22%). In addition, ENA-78 appears to activate neutrophils through the IL-8 receptor. Since both in vitro and in vivo biological fluids may contain an array of chemotactic cytokines that may be relevant to the activation and chemotaxis of neutrophils, we have developed a highly specific and sensitive sandwich ELISA for the detection of ENA-78. PMID- 1428027 TI - ras-oncogene mutation and pancreatic adenocarcinoma. PMID- 1428028 TI - Interferon therapy for chronic NANB hepatitis. PMID- 1428029 TI - Does Helicobacter pylori cause gastric cancer? PMID- 1428030 TI - Tense ascites redefined: renal consequences of tense ascites in decompensated cirrhotics. AB - Cirrhotics with tense ascites fail to achieve increased diuresis in the supine position. To assess the role of inferior vena cava compression in this phenomenon, we studied cirrhotics with mild to moderate (n = 11) and tense (n = 2) ascites, and patients with membranous inferior vena cava obstruction (n = 2) before and after balloon dilatation, in the sitting, supine and 10 degrees head down tilted positions for 2 hours each. Urinary output (p < 0.005), creatinine clearance (p < 0.025) and sodium excretion (p < 0.025) increased in cirrhotics with mild to moderate ascites in the supine position, and further in the head down position. Similar changes occurred in patients with inferior vena cava membrane. In cirrhotics with tense ascites, these parameters did not change significantly in the supine position, but increased in the head down position. We conclude that failure to augment diuresis in the supine position in cirrhotics with tense ascites is not due to inferior vena cava obstruction alone but is probably also due to compression of the collateral vessels. This clinical observation may serve as a criterion for diagnosing tense ascites. PMID- 1428031 TI - Magnetic resonance imaging in pancreatic diseases: comparison with other imaging techniques. AB - Magnetic resonance imaging (MR) was performed in 14 healthy subjects and 16 patients with pancreatic disease. All the 16 patients were subjected to ultrasonography (USG), computed tomography (CT) and MR while endoscopic retrograde cholangiopancreatography (ERCP) was performed in 10 cases. In one patients with adenocarcinoma and two with gastrinoma, MR demonstrated abnormalities while USG and CT were normal. MR was, however, inferior to ERCP in demonstrating ductal abnormalities in chronic pancreatitis. Our initial experience suggests that MR is superior to other imaging modalities in the diagnosis and staging of pancreatic tumors; however, it is inferior to ERCP in the diagnosis of pancreatitis. PMID- 1428032 TI - Gastrointestinal endoscope disinfection practices in India: results of a national survey. AB - A questionnaire was sent to 435 endoscopy centers in the country to obtain information regarding current endoscopic disinfection practices. Of these, 133 (30.6%) centers responded. Adequate disinfection (a minimum exposure to 1% glutaraldehyde for 2 minutes) before the start of endoscopy sessions and between procedures was practised in 61 (46%) and 45 (34%) centers respectively. The proportion of centers practising adequate disinfection was similar among those performing < 1500 and > 1500 endoscopies/year (50% vs 36%; p = ns). Twenty two (17%) centers used some additional precautions in patients with hepatitis B virus infection or immunocompromised states. Two (1.5%) of the 133 centers performing upper GI endoscopies and eight (18%) of the 44 centers performing ERCP examinations reported occurrence of infections following these procedures. Allergic reactions to disinfectants were reported by five (4%) centers. We conclude that only about a third of the gastroenterology centers in the country are practising adequate endoscope disinfection routinely. PMID- 1428033 TI - Out-patient esophageal dilation: an experience in 130 patients using Savary Gilliard dilators. AB - Experience of outpatient esophageal dilation using Savary-Gilliard dilators in 130 patients during a 17 month period is reported. The strictures were radiation induced (48), tumoral stenoses (40), anastomotic (16) and due to other causes (26). Both fluoroscopy and endoscopy were used in 58%, endoscopy alone in 23% and fluoroscopy alone in 19% of patients for placement of the guide wire. One hundred and twenty six stricture dilations (97%) were technically successful. Eighty one (62%) patients could be dilated to 14 mm or more. One hundred and nineteen (94%) patients were dilated in one or two sessions. Among the 109 patients who followed up, dilation was successful in providing adequate dysphagia relief in 97 patients and facilitated the performance of other therapies in 9 patients. Major complications included severe continuous chest pain (1 case), hematemesis (2), fever (4) and transient stridor (2). The patient with persistent pain and 9 patients undergoing other therapies required hospitalization. There were no perforations or death. We conclude that esophageal dilation with Savary-Gilliard dilators is safe and effective even in tumors and post-radiation strictures. It can be performed on an outpatient basis in a majority of patients. PMID- 1428034 TI - Endoscopic sclerotherapy versus propranolol in prevention of recurrent variceal bleeding in patients with child's B and C cirrhosis: a preliminary report. AB - Thirty two patients with cirrhosis of the liver of Child's B and C class and an episode of endoscopically proven variceal bleed were randomly assigned to receive endoscopic sclerotherapy (EST) or oral propranolol for the prevention of recurrent upper gastrointestinal bleeding. EST was performed at 3 week intervals using 1% polidocanol intravariceally, till eradication of varices. Propranolol dose was adjusted to reduce the resting heart rate by 25% of the basal value (mean +/- SD, 194.3 +/- 63.9 mg/day) Two patients in the propranolol group were excluded within 48 hours due to side effects of the drug. Thirty patients (EST 16, propranolol-14) completed the trial. Patients were followed up for a maximum of 480 days. Mean follow-up in the EST and propranolol groups was 217 and 243 days respectively. The median bleeding free intervals were 480 and 194 days and number of rebleeding episodes was eight and 16 respectively in the EST and propranolol groups (both p = ns). Our study suggests a trend in favor of EST in preventing variceal rebleeding in patients with hepatic cirrhosis who belong to Child's B and C classes. PMID- 1428035 TI - Comparative study of omeprazole and famotidine in the treatment of duodenal ulcer. AB - In a double blind, multicenter, parallel group clinical trial in patients with symptomatic duodenal ulcers, 129 patients were randomized to receive either omeprazole 20 mg once daily (n = 65) or famotidine 40 mg once daily (n = 64) for 2 weeks, and if the ulcers were not healed, for a total of 4 weeks. Seventy four percent of these receiving omeprazole had healed ulcers after 2 weeks compared with 34.3% of those receiving famotidine (p < 0.001). At 4 weeks, the respective figures were 97.3% and 77.6% (p < 0.001). After 2 weeks of treatment, only 11.1% and 29.8% of omeprazole and famotidine treated patients respectively had day time pain (p < 0.02). Diary cards (successfully completed by 2/3rd of patients) showed that omeprazole treated patients required smaller amounts of antacids (p = ns). Over the first two weeks, ulcer healing rate was similar in smokers and non- smokers. No significant side effects were reported in either group. Omeprazole 20 mg/day provides more rapid relief of symptoms and heals a greater proportion of duodenal ulcers at 2 and 4 weeks than famotidine 40 mg/day. PMID- 1428036 TI - A study of Helicobacter pylori in north Indian subjects with non-ulcer dyspepsia. AB - A prospective case control study was conducted in 50 patients with non-ulcer dyspepsia (NUD) and 10 age and sex matched controls to determine the prevalence of Helicobacter pylori in patients with NUD and to correlate symptoms, histology and presence of H pylori in gastric biopsies. Endoscopic biopsies from antrum and fundus were subjected to urease test and histological examination. On histology, H pylori was identified in 27 (54%) NUD patients and in one of 10 controls. Urease test was positive in 31 (62%) antral and 21 (42%) fundal biopsies in patients with NUD and in only one (10%) of 10 antral biopsies in the control group. On histology, gastritis was present in the antrum in 46 (92%) NUD patients and in the fundus in 40 (80%) cases; of these, 27 (54%) and 15 (30%) had H pylori in antral and fundal biopsies respectively. The severity of antral gastritis correlated with the density of H pylori (p < 0.05). PMID- 1428038 TI - Pathophysiology and immunobiology of Giardia lamblia infection. PMID- 1428037 TI - Frequency of hepatitis B, C and D and human immunodeficiency virus infections in multi-transfused thalassemics. AB - Of forty multi-transfused thalassemia patients (26 males, 14 females; mean age 8.1 +/- 5.3 years, range 1-35) with no clinical or biochemical evidence of liver disease, HBsAg, anti-hepatitis C virus and anti-human immunodeficiency virus antibodies were present in 18 (45%), 7 (17.5%) and 1 (2.5%) cases respectively. Three of the 18 (16.7%) HBsAg positive patients were anti-delta antibody positive. Our results indicate that more than 50% of multi-transfused thalassemia patients show serological evidence of one or more of hepatitis B, C and D and human immunodeficiency virus infection. PMID- 1428039 TI - Gastric ulcer due to metastasis from carcinoma cervix. PMID- 1428040 TI - Coarctation of inferior vena cava in situs inversus totalis. AB - A woman aged 28 years with situs inversus totalis presented with chronic Budd Chiari syndrome with symptoms of 3 years' duration. The left sided inferior vena cava was occluded below the diaphragm above a patent morphologic right hepatic vein. A dorsal cavoatrial bypass was attempted but abandoned due to bleeding from extensive collaterals. The occurrence of coarctation of the inferior vena cava in situs inversus totalis lends support to the view that it is a congenital condition and occurs due to disturbance in fusion of the hepatic segment of the inferior vena cava and the hepatocardiac channel. PMID- 1428041 TI - Giant colonic diverticulae presenting as painless abdominal lump. PMID- 1428043 TI - Intestinal endometriosis. AB - Two cases with intestinal endometriosis, one with a right iliac fossa mass and the other with subacute intestinal obstruction, are presented. In both the cases, the diagnosis was not suspected clinically and was reached only on histological examination of the resected specimens. PMID- 1428042 TI - Periampullary carcinoma in a young female with situs inversus. AB - Periampullary carcinoma in a young female with situs inversus viscerum is reported. Endoscopy was difficult because of the altered anatomy. PMID- 1428044 TI - Intussuscepting ileal hemangioma with perforation. AB - A rare case of solitary intussuscepting capillary hemangioma in the distal ileum with perforation and peritonitis is presented. The diagnosis was made only at surgery for presumed acute intestinal obstruction. PMID- 1428045 TI - Thrombolytic therapy in thrombotic obstruction of inferior vena cava. PMID- 1428046 TI - Vascular lesions in abdominal tuberculosis. PMID- 1428047 TI - Extracolonic complications in ulcerative colitis. PMID- 1428048 TI - Intermittent intravenous pulse cyclophosphamide treatment in systemic lupus erythematosus. AB - To determine the efficacy and safety of intermittent intravenous pulse cyclophosphamide in patients of severe systemic lupus erythematosus (SLE), 50 patients having severe/refractory lupus nephritis, vasculitis or neuropsychiatric manifestations were treated with 3 weekly pulses of cyclophosphamide for 6 such pulses. This treatment was found to be associated with significant and sustained improvement during a 2 yr follow up with respect to the mean renal activity score, individual renal parameters (proteinuria, erythrocyturia, and serum creatinine levels), focal neurological manifestations, vasculitic lesions, antinuclear antibody titers, complement component C3, anti-dsDNA antibodies levels and ESR. There was a sustained decrease in the overall mean disease activity score, and the mean daily dose of prednisolone (pretreatment 32.62 mg daily to 3.75 mg daily after 24 months). There was a significant decline in the percentage and absolute B cell count after 7, 14 and 21 days of this treatment. Effect on other lymphocyte subsets (CD3+, CD4+ and CD8+) was not marked. Pulse cyclophosphamide could therefore be an effective and less toxic form of treatment in patients with SLE having severe lupus nephritis, focal neurological lesions or vasculitis. PMID- 1428049 TI - In vitro effect of intravenous immunoglobulin supplementation on serum opsonic activity in tracheostomised patients. AB - An in vitro study of the effect of immunoglobulins (mainly IgG) on opsonophagocytic activity of polymorphs was carried out in 17 tracheostomised patients admitted in medical intensive care unit of our hospital. The opsonic and phagocytic activities were tested against Staphylococcus aureus by modified polymorphonuclear leucocyte overlay method; and serum IgG and serum IgM levels were estimated by single radial immunodiffusion technique. As compared to healthy volunteers, opsonophagocytic activity was significantly lower in tracheostomised patients. However, this activity improved markedly after immunoglobulin supplementation (P less than 0.01). The same degree of enhancement was also observed in normal controls. PMID- 1428050 TI - Alloimmunisation to platelet transfusions in the Indian patients. AB - Twenty nine patients of acute and chronic leukemia undergoing chemotherapy and receiving blood transfusions (BT) and platelet transfusions (PT) from random donors (3-20 PT from 4-56 donors) were followed up for alloimmunisation using the platelet immunofluorescence test. Two women patients aged 65 and 28 yr reacted positive. Both patients had received multiple BT but no PT at the time of testing. Both were parous women. Our results point to the need to test for alloimmunisation prior to starting PT in parous women who have received multiple BT, although a study on larger number of patients is necessary for confirmation. PMID- 1428051 TI - Epidemiological study of coronary heart disease in Gujaratis in Delhi (India). AB - A community based survey of coronary heart disease (CHD) was carried out in Gujarati families settled in Delhi. The number of adults surveyed in the age group 25-64 yr was 1317. CHD was diagnosed either on the basis of clinical history supported by documentary evidence of treatment in the hospital or at home or on ECG evidence in accordance with the Minnesota Code. The prevalence rate of CHD on clinical history was 25.1 (28.2 in males and 22.4 in females) per 1000 adults (25-64 yr). The prevalence rates were slightly lower in Gujaratis than the general Delhi urban population. The prevalence rate based on both clinical history and ECG criteria was estimated at 66.8 as compared to 96.8/1000 in general urban Delhi population. The risk factors for CHD such as socio-economic status, family history, obesity, smoking, physical activity and hypertension were studied. The mean and 5th, 50th and 95th percentile values of blood lipids were also estimated in CHD patients and compared with the control group. Hypertension ranked the leading risk factor. Prevalence rate of CHD was higher in the upper socioeconomic group. The positive correlation of higher levels of serum lipids e.g., total cholesterol, low density lipoprotein cholesterol (LDL-C) and triglyceride with CHD was confirmed. PMID- 1428052 TI - A rapid survey on substance abuse disorders in the urban slums of New Delhi. AB - The results are presented of a rapid survey screening method of general population for identifying dependent and non dependent drug abusers, especially in vulnerable groups such as slum dwellers. The results showed that with the help of instrument with modified DSM III and interviewing only the heads of the households it was possible to get reliable estimates of dependence disorder in the community. This method can be of assistance to health planners for a quick assessment of the magnitude of the problem leading to better allocation of funds and developing services for the affected population. The method is an improvement on key informant technique and a full fledged survey. PMID- 1428053 TI - Comparative influence of vanillin & capsaicin on liver & blood lipids in the rat. AB - The influence of vanillin (0.15 mg %) and capsaicin (0.3 mg %) on liver and blood lipids in growing female Wistar rats was determined, when fed along with a normal diet. Vanillin, like capsaicin, decreased the serum triglycerides and the triglycerides associated with lipoproteins viz., VLDL+LDL and HDL with a tendency to lower liver triglycerides as well. Cholesterol and phospholipids in liver and serum were unaffected. The accumulation of triglycerides in serum after Triton WR 1339 blocking was higher in animals fed a vanillin supplemented normal or hypertriglyceridemic diet than in the corresponding controls. The accumulation of triglycerides in serum with capsaicin supplementation with either diet was much higher than with vanillin supplementation. PMID- 1428054 TI - Comparative study on determination of alpha-hydroxybutyrate dehydrogenase, lactate dehydrogenase isoenzyme LDH-1 by adsorption on DEAE Sephadex A-50 & electrophoresis. AB - Serum alpha-hydroxybutyrate dehydrogenase (HBDH) and lactate dehydrogenase isoenzyme (LDH-1) levels by two techniques viz., adsorption on DEAE Sephadex A-50 and by electrophoresis were estimated in healthy subjects and patients with testicular tumours. The correlation coefficient between HBDH and LDH-1 by adsorption technique was found to be r = 0.8. HBDH was found to have a value almost twice that of LDH-1 by adsorption and electrophoretic technique and the activity of LDH-1 obtained by two methods and of HBDH in normals and patients with testicular tumours could be converted using a factor of 0.557. The quantitative method used for determination of HBDH is reliable, accurate, simple and rapid and therefore has better value in a clinical setting than electrophoresis and adsorption techniques which are laborious and time consuming. PMID- 1428055 TI - Computed tomographic evaluation of pineal calcification. AB - A prospective study to ascertain the incidence of normally calcified pineal gland, was carried out in 1000 consecutive patients from different parts of Uttar Pradesh (India), undergoing cranial computed tomography for reasons other than a pineal or parapineal pathology. A total of 167 (16.70%) patients were found to have calcified pineals. Of these 128 were males and 39 females. The incidence rose from 1.16 per cent in the first decade to 31.88 per cent above the age of 50 yr. The percentage incidence of normal pineal calcification was lower than that seen in the Western population. No significant difference was found between men and women in any age group. Although calcification appeared as early as the first decade, this percentage was significantly lower than in the higher age groups. Significantly higher incidence rates were seen in the second decade, third decade and sixth decade onwards. PMID- 1428056 TI - Antimutagenic activity of plumbagin in Ames Salmonella typhimurium test. AB - This paper reports the antimutagenic activity of plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone) against certain known chemical mutagens in a standard mutagenicity test system of Ames using S. typhimurium strains. Plumbagin by itself did not show any mutagenic effect, whereas it reduced significantly the mutagenic effect of 4-nitrophenylene diammine, phenyl hydrazine and sodium azide in test strains of S. typhimurium, suggesting that plumbagin possessed antimutagenic activity. PMID- 1428057 TI - Ultrastructural study of mixed growth hormone & prolactin secreting pituitary adenomas. AB - An ultrastructural study was done on 15 mixed growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas surgically removed from acromegalic patients with hyper-prolactinaemia, in order to see whether the 2 hormones were present in the same cell or in different cells. Double labelling immunogold technique was used for simultaneous ultrastructural localization of GH and PRL. It was found that each neoplastic cell in these 15 tumours (30 to 50 cells were studied in each case) contained 4 populations of granules viz., (i) granules positive for only GH; (ii) granules positive for only PRL; (iii) granules positive for both GH and PRL; and (iv) granules negative for both GH and PRL (unlabelled). Though the relative percentage of these 4 types of granules varied from cell to cell even within the same tumour, the major population (49.9 to 96%) was constituted by the mixed granules showing labelling for both GH and PRL. Almost all the cells examined from each tumour appeared to be mammosomatotrophs. Thus, the study indicated that mammosomatotroph adenomas are perhaps more common among mixed GH and PRL--secreting pituitary adenomas than previously believed. It could be important to recognize these tumours from the therapeutic point of view. PMID- 1428058 TI - Incidence of abnormalities in sperm morphology as an indicator of its fertilizing potential. AB - A retrospective analysis was carried out to assess the correlation of sperm morphology with the occurrence of fertilization in vitro of human oocytes. Seventy women who were subjected to in vitro fertilization procedure were taken up for this study. The cytological smears of semen were evaluated for the morphological characteristics of spermatozoa. Instances where in vitro fertilization did not occur (group II) had significantly (P less than 0.001) higher morphological abnormalities (head defects) when compared with those where fertilization occurred in vitro (group I). The results indicate that evaluation of sperm morphology with special reference to head abnormalities has diagnostic potential in human in vitro fertilization. PMID- 1428060 TI - DNA analysis of breast cancer by flow cytometry & correlation with other prognostic parameters. AB - Flow cytometric estimation of DNA content (ploidy and S-phase fraction--SpF) was done on breast cancer tissues from 171 patients. Twenty eight per cent of the tumours were diploid and 72 per cent were aneuploid. SpF was measurable in 82 DNA histograms; of these 22.4 per cent had SpF less than 10 per cent, 34.1 per cent had SpF between 10-20 and 43.5 per cent had SpF greater than 20 per cent. The mean SpF of the measurable histograms was 19.01 per cent with a range 1.78 to 45.19 per cent. A significant correlation between DNA ploidy and SpF was observed (P less than 0.01). Eighty nine per cent of diploid tumours had SpF less than 10 per cent and 73 per cent of aneuploid tumours had SpF greater than 20 per cent. A significant correlation was also found between ploidy and SpF and oestrogen receptor (ER) status of the tumours (P less than 0.05) and between SpF and progesterone receptor (PgR) status of the tumours (P less than 0.05), but not between ploidy and PgR status of the tumours. A significant direct correlation was observed between SpF and tumour grade (P less than 0.05), but not between ploidy and tumour grade. No correlation was observed between DNA ploidy and SpF and tumour type, tumour size, axillary lymph node involvement, age and menopausal status of the patients. Although the incidence of breast cancer is one-third of that reported in the Western countries, there is apparently no biological difference between the various parameters studied. PMID- 1428059 TI - Neutralization potency of Russell's viper venom toxoid antivenom, as compared with standard antivenom. AB - Rabbits were immunized with gamma (gamma) irradiated Russell's viper venom toxoid, adsorbed to aluminium phosphate adjuvant. Antibody (raised against toxoid inoculation) titer was compared to a commercial antivenom on the basis of its ability to neutralize hemorrhagic, necrotic and lethal effects of viper venom. Toxoid immunization (on day 0, 15 and 30) produced antivenom which showed approximately one-third antilethal, half antihemorrhagic and antinecrotic titers as compared to those of the commercial hyperimmunized, concentrated horse antivenom. PMID- 1428062 TI - Isolation & characterization of angiogenic factors from cultured cells & conditioned media. AB - Angiogenic factors were isolated by ion exchange chromatography from three established cell lines viz., HEp 2, HeLa and CHO, a primary culture of mouse mammary adenocarcinoma and from conditioned media of HEp2 and cultured mammary adenocarcinoma cells. The angiogenic activity was assayed by chicken chorioallantoic membrane assay. The angiogenic factor eluted at 0.5 M, exhibited lambda max at 258 +/- 1 nm, contained protein and nucleic acid. The cellular angiogenic factor showed a ratio of 1:1 for protein and nucleic acid whereas the secreted angiogenic factor had 3-5 parts of protein to 1 part of nucleic acid. The angiogenic factor from HEp2 and CHO cells did not bind to heparin-agarose. Microheterogeneity of the angiogenic factors was established by SDS-PAGE. Antiserum raised against the cellular angiogenic factor from HEp2 cells, showed a titre of 1:1600 by ELISA. The angiogenic factor was directly localized on whole cells by ELISA. Cellular as well as secreted angiogenic factors crossreacted with the antibody. Neutralizing effect of the antiserum on induction of angiogenesis was detected on chicken chorioallantoic membrane. PMID- 1428061 TI - Impairment in cellular protein phosphorylation by mitogen activated lymphocytes from patients with Hodgkin's disease. AB - T cell activation process in patients of Hodgkin's disease was studied in terms of cellular protein phosphorylation following interaction of T lymphocytes with mitogen PHA. Peripheral blood lymphocytes from Hodgkin's disease patients and healthy donors, labelled with [32P] were activated with PHA. The cell lysates were subjected to SDS-PAGE, 2-dimensional gel analysis and were autoradiographed. It was observed that lymphocytes from both Hodgkin's disease patients and healthy donors followed similar time kinetics of phosphorylation. Nine of the eleven major protein bands, resolved on SDS-PAGE in the molecular weight range of 15.7 98 kD showed reduced phosphorylation (ratios of densitometric readings taken after and before stimulation) compared to that of healthy donors. Isoelectric focusing of these major protein bands in 2-dimensional gels further resolved them into about 27 proteins. Most of these showed increased phosphorylation in lysates of activated lymphocytes from healthy donors compared to that of Hodgkin's disease patients. The results showed a defect even at an early stage in terms of inadequate cellular protein phosphorylation. PMID- 1428063 TI - Immunohistochemical, ultrastructural & immunoelectron microscopic study of glial fibrillary acidic protein in corpora amylacea. AB - Brain tissues from 10 patients (of non-neurological disease) were studied for the presence of corpora amylacea (CA) using light microscopy (LM), immunohistochemistry (IH) for localisation of glial fibrillary acidic protein (GFAP) and transmission electron microscopy (TEM). Immunoelectron microscopy (IEM) by post-embedding technique using colloidal gold was also performed in two of these patients for more precise localisation of GFAP. Three types of immunoreactivity were noted by IH under LM; some CA were completely negative for GFAP (type III), while others showed positivity, which was either diffuse (type I) or confined to the periphery (rim positivity-type II). TEM showed variable sizes in electron dense material in the centre associated with different amounts of glial filaments (GFs) at the periphery. Thus the different types of IH staining appeared to corroborate with the presence and amount of GFs in CA. The sensitive technique of IEM confirmed the presence of GFAP in all CA irrespective of their IH typing at LM. It is suggested that CA formation in astrocytes is associated with progressive fragmentation and disintegration of GFs with resulting increase in the accumulation of electron dense GFAP-negative material. As more and more of GFs get incorporated and disintegrated, it results in increase in the size of the CA. Thus, the present study clearly demonstrates that GFAP in the GFs contributes to the composition of CA. PMID- 1428064 TI - Energy intake & resting metabolic rate of young Indian men & women. AB - Energy intake, body weight and resting metabolic rate (RMR) were measured on seven days consecutively, in 20 men and 14 women on ad libitum food intake under free-living conditions. These measurements were repeated in 8 men and 9 women twice with an interval of two months. Mean energy intake (EI) as measured by 'Weightment' method, was 2820 +/- 577 kcal/d in men and 1611 +/- 147 kcal/d in women. EI showed significant differences between weeks (P less than 0.01, CV = 13.1% in men and 9.5% in women) and between subjects (P less than 0.05, CV = 13.7% in men and 9.8% in women). Intra individual variance contributed up to 60 to 70 per cent of the total variance in EI in both the groups. RMR measured by using Oxylog, varied between the three periods (CV = 6% in men and 5.9% in women) and between subjects (CV = 5.7% in men and 12.3% in women). Mean RMR of both men and women was lower than the predicted value by FAO/WHO/UNU equation. Estimate of mean 24 h energy expenditure, using activity diary and factorial method, in the first round was 2458 +/- 144 kcal in men and 1655 +/- 172 in women, resulting in an energy balance of 308 kcal in men and -44 kcal/d in women. The pattern of activity remained the same in the three rounds for both groups. There were no significant changes in weight (CV-1.6%) or per cent body fat during the study period (P greater than 0.1). PMID- 1428065 TI - Reliability of skinfold calipers as a tool for measuring body fat in human beings. AB - Triceps skinfold thickness measured in ten adults aged 19 to 50 yr by a Holtain skinfold caliper, was compared with subcutaneous fat thickness obtained on cross sections of the left upper arm by computerized axial tomography (CAT). The thickness of subcutaneous fat was measured on CAT scan film directly with the inbuilt computer graphic technique. The measurements taken on CAT scan film were found to be significantly higher (by 21-45%; P less than 0.001) than those by the skinfold calipers. Our findings suggest that skinfold calipers may not be very accurate tools for the assessment of body fat in human beings. Therefore, its use in the determination of body composition, for which great precision is required calls for re-thinking. PMID- 1428066 TI - Use of rat jejunum for assay of acetylcholine. AB - Experiments were carried out to determine the advantage in using isolated rat jejunum in the assay of acetylcholine (ACh) in preference to other tissues. Rat jejunum was found to be sensitive to ACh 0.01 micrograms, 5-hydroxytryptamine (5HT) 0.2 to 0.5 microgram and least sensitive to histamine. (Ach greater than 5HT greater than histamine). PMID- 1428067 TI - Analysis of the major surfactant-associated proteins in human lung. AB - The protein component of human pulmonary surfactant was analysed. A purified surfactant preparation, after delipidation, was subjected to gel filtration on Sephadex G-200. The proteins present in the surfactant were categorised by means of SDS-polyacrylamide gel electrophoresis into serum and non-serum components. Molecular masses determination showed the presence of three sub-groups with molecular masses of 60-68 kDa, 28-36 kDa and 10-18 kDa, respectively. Antiserum generated against 28-36 kDa protein strongly reacted with the purified surfactant and amniotic fluid, while it did not show any cross reactivity with other groups of proteins and serum in a double diffusion immunoprecipitation assay. We propose that this protein is the major non-serum surfactant-associated protein present in human lung surfactant. PMID- 1428068 TI - Ascorbic acid status in uremics. AB - Plasma levels of ascorbic acid (AA) and dehydroascorbic acid (DHA) were estimated in 27 patients of end stage renal failure (ESRF) on standard conservative therapy (group A) and 9 patients of ESRF on maintenance haemodialysis (MHD; group B). Fourteen healthy subjects matched for age and sex served as control (group C). The dietary intake of vitamin C was significantly decreased in group A than in group B compared to control. Similarly, plasma AA was significantly lowered to 0.801 +/- 0.283 mg per cent in group A compared to 1.421 +/- 0.47 mg per cent in control. While it was just lowered to 1.058 +/- 0.272 mg per cent in group B. Although plasma level of DHA was raised to 0.243 +/- 0.486 mg per cent and 0.166 +/- 0.54 mg per cent in groups A and B respectively, the increase was not statistically significant. In our present study, the DHA/AA ratio was found to be inversely proportional to the plasma AA. Further, this ratio has been claimed to be a better indicator of overall reducing atmosphere (i.e., profile of vitamin C) of the body. PMID- 1428069 TI - Auditory evoked response in patients of diabetes mellitus. AB - Brainstem auditory evoked response (BAER) and the mid latency response (MLR) were recorded in 25 diabetic men and compared with a group of 25 control subjects. The threshold of hearing was higher (P less than 0.001) in the patients. The BAER peak latencies were also significantly prolonged in both the ears; however, the degree of prolongation was more prominent in the right ear. The interpeak latencies of waves I-III were also prolonged (P less than 0.01) in the left ear, with non significant increase noticed in the right ear also. The wave V amplitude was lower (P less than 0.05) in diabetics. The MLR, on the other hand, was not affected in patients. These findings suggest functional impairment in the auditory pathway in patients of diabetes mellitus. PMID- 1428071 TI - Secondary immune defects in non-Hodgkin's lymphoma. AB - Changes in the humoral, cellular and phagocytic components of the immune system were investigated in 44 biopsy proven, untreated patients of non-Hodgkin's lymphoma (NHL). There was significant decrease in the total lymphocyte number, their subsets (T and B) and the T helper (T mu) population. Impaired leukocyte migration inhibition response and DNA synthesis following stimulation by phytohaemagglutinin were noted. Significant reduction of serum IgA was found in patients of both diffuse and nodular NHL. Phagocytic activity and nitroblue tetrazolium (NBT) reduction were unaltered, but chemotaxis was significantly reduced and bactericidal activity showed variable results. PMID- 1428070 TI - Prevalence & pathogenesis of hypophosphatemia in ventilated patients. AB - Hypophosphatemia was found in 12 (43%) patients within 24-36 h of mechanical ventilation in a group of 28 patients in an intensive care unit. The hypophosphatemic patients had a significant lowering of renal phosphorus threshold (P = 0.005) and inappropriate phosphaturia. These abnormalities resolved once ventilation was discontinued. Serum parathyroid hormone (PTH) levels were unaltered in this group of patients suggesting that some factor other than PTH was responsible for hypophosphatemia. This study has demonstrated that abnormalities of renal phosphate handling can cause hypophosphatemia in ventilated patients. PMID- 1428072 TI - Characterization of G6PD Rohini--a new class III Indian variant. AB - A new Indian G6PD variant was detected in a 15 yr old Maratha male during a population screening programme in high school children in Bombay (India). The propositus and two family members having the same variant were apparently healthy. This enzyme variant has a mild erythrocyte G6PD deficiency and a slow electrophoretic mobility. It is characterized by a high Michaelis-Menton constant for G6P, a bimodal curve for pH optima and a slight decrease in the thermostability. The rate of utilization of substrate analogue is similar to that of normal. These observations suggest identification of a new class III variant, designated as G6PD Rohini. PMID- 1428073 TI - Treatment of intractable spasticity in spinal cord injured patients. AB - Spasticity and flexor spasms can be most incapacitating in SCI victims. Muscle relaxants, physiotherapy and elimination of triggering factors must be tried before opting for peripheral surgery or alcohol block. The choice of alcohol block or peripheral surgery depends in whether damage to the spinal cord is complete or incomplete. Results of both the procedures are satisfactory in rightly chosen patients. Alcohol block is a simple, safe and effective method of treating spasticity in the patients of complete paraplegia. The effect is immediate and almost permanent. However, alcohol block is contra-indicated in the patients of incomplete paraplegia where peripheral surgery is a better choice. PMID- 1428074 TI - Diabetes mellitus in Libya: a retrospective study. AB - The records of the Diabetes Hospital, Tripoli, Libya for the years 1961-1983 were examined and the available particulars relating to 24,962 diabetic patients (12,486 males + 12,476 females) registered during this period were obtained. The highest number of male and female diabetic patients were in the age group 40-50 years and the highest number of obese diabetic patients also belong to this age group. There was a gradual increase in the number of diabetic patients visiting the Diabetes Hospital with the highest number in 1983. The increase has been both in the type I and type II patients. In 1983, 15% of the diabetic patients belong to type I diabetes. Family history of diabetes appears to be an important factor in the onset and manifestation of type II diabetes. Patients with diabetes in the family have a lower mean body mass index and fasting blood glucose level as compared with those of patients without known case of diabetes in the family. This may be due to greater alertness, early diagnosis of the disease and steps taken to control blood glucose levels and body weight in the case of patients with family history of diabetes. PMID- 1428075 TI - Unusual manifestations of myxoedema. AB - The lesser known manifestations of myxoedema encompass a wide spectrum of neurologic, psychiatric, endocrinologic and autoimmune pathology that mask obvious clinical diagnosis. Interesting head and neck presentations are discussed. The relationships with the Pendred and Down syndromes raise hereditary and genetic considerations. PMID- 1428076 TI - Mechanisms of carcinogenesis in risk identification. Introduction. PMID- 1428077 TI - Mechanisms of Carcinogenesis in Risk Identification. IARC Working Group Meeting. Lyon, 11-18 June 1991. PMID- 1428078 TI - Mechanisms of action of known human carcinogens. AB - Mutational mechanisms can be proposed for most, if not all, known human carcinogens. Many of these are electrophilic or metabolically activated to reactive molecules which can alter DNA, causing genetic damage and different types of mutations. Even some human carcinogens previously proposed to be nongenotoxic (e.g., hormones and asbestos) exhibit mutational activity in assays for chromosomal mutations. Since such chemicals are usually inactive in the Salmonella assay and other assays for gene mutation, more emphasis has been placed on their nonmutational mechanisms. Clear evidence exists that these carcinogens can alter gene expression and stimulate cell proliferation by epigenetic mechanisms. Such properties are undoubtedly important in their carcinogenic activity. Although they are less well studied, DNA reactive, genotoxic carcinogens also alter gene expression and increase cell turnover by epigenetic mechanisms. These findings are consistent with the current understanding of the molecular basis of multistep carcinogenesis. Most common human cancers evolve as the result of multiple mutational events. The molecular basis of these mutations is varied, and they include point mutations, deletion mutations, chromosomal rearrangements, gene amplification and chromosomal losses and gains. Therefore, different mutational activities of carcinogens can influence the carcinogenic process at different steps. Influences on gene expression and cell proliferation are also important in allowing clonal expansion of preneoplastic cells and in disrupting the suppressive effects of surrounding normal cells on preneoplastic cells (Dotto et al., 1988). The mechanisms of action of human carcinogens, and very probably many rodent carcinogens, include both genetic and epigenetic processes. Carcinogenesis is a multistep, multigenic, multicausal process (Barrett, 1987b), so both epigenetic and genetic factors are probably important.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428079 TI - Use of short-term tests in determining the genotoxicity or nongenotoxicity of chemicals. AB - This article brings together the several current approaches to the use of short term tests for identifying carcinogens and the several meanings of the term 'genotoxic'. Examples of genotoxic and nongenotoxic carcinogens and of genotoxic and nongenotoxic mechanisms of carcinogenesis are discussed. Emphasis is placed on the determination of genotoxicity as it affects evaluation of the mechanism of action of a new rodent carcinogen. PMID- 1428080 TI - Performance of tests for cell transformation and gap-junction intercellular communication for detecting nongenotoxic carcinogenic activity. PMID- 1428081 TI - Genotoxic and nongenotoxic carcinogens: mechanisms of action and testing strategies. PMID- 1428082 TI - Use of 32P-postlabelling to distinguish between genotoxic and nongenotoxic carcinogens. PMID- 1428083 TI - Peroxisome proliferation and hepatocarcinogenesis. PMID- 1428084 TI - Immunosuppression and cancer. PMID- 1428085 TI - Sex hormones and cancer. AB - There are few instances in which a clear effect of hormones on cancer risk is known and in which the effects of those hormones on the cells concerned are also known. The best examples are the relationships between sex hormones and cancer in women. The effects of sex hormones both on the risk for endometrial cancer and on the cells of the endometrium are well understood, and the evidence strongly suggests that hormones act by altering the rate of cell division. The same mechanism may explain the relationships between sex hormones and the risk for breast cancer, but our understanding of cancers at this site is incomplete. Less still is known about the mechanisms of the effects of sex hormones on other hormone-related cancers, such as those of the ovary and cervix. Most sex hormones are not genotoxic. PMID- 1428086 TI - Structure-activity relationships for carcinogens with different modes of action. AB - The application of structure-activity concepts to the elucidation of the action of chemical carcinogens may proceed by two approaches: the hypothesis and the knowledge-based approaches. The former, exemplified by the 'structural alerts' devised by Ashby and associates, derives from the recognition of the electrophilic nature of carcinogens that damage DNA. The latter approach does not assume an a priori mechanism of action but derives information from the establishment of relationships between structural features and carcinogenicity. Indeed, the 'structural alerts' of Ashby et al. are recognized by such an approach; however, if structural features are associated with the activity of 'nongenotoxic' carcinogens, they would also be recognized by the knowledge-based approach. Obviously, the recognition of new (nonelectrophilic) structural features associated with carcinogenicity will lead to testable hypotheses. PMID- 1428087 TI - Chemically induced cell proliferation in carcinogenesis. AB - Carcinogenesis can proceed by a variety of pathways involving the sequential mutation of normal cellular growth control genes and the clonal expansion of the resulting precancerous or cancerous cells. Chemical carcinogens may act by inducing mutations and/or altering cellular growth control. One class of chemical carcinogens are the genotoxicants. These compounds or their metabolites are DNA reactive and directly induce mutations or clastogenic changes. The observation that most mutagens are also carcinogenic is the basis for many current predictive assays and risk assessment models; however, there are different classes of nongenotoxic carcinogens that do not interact with DNA. Mitogens directly induce cell proliferation in the target tissue; cytotoxicants produce cell death followed by regenerative cell proliferation. Differential toxicity and/or growth stimulation induced by mitogens and cytotoxicants may provide a preferential growth advantage to spontaneous or chemically induced precancerous or cancerous cells. Mutagens are much more effective carcinogens at doses that also induce cell proliferation, and mutational activity may occur as an event secondary to cell proliferation. Thus, chemically induced cell proliferation is an important mechanistic consideration for both genotoxic and nongenotoxic carcinogens. The complex quantitative relationships between chemically induced cell proliferation and carcinogenic activity are under study in many laboratories. Such information should be considered in setting doses for cancer bioassays, for classifying chemical carcinogens and in providing more realistic approaches to risk assessment. Of particular concern in extrapolating cancer risk from rodent models to humans are those nongenotoxic agents that exhibit carcinogenic activity only at doses that also produce cytolethality and regenerative cell proliferation in the target organ. PMID- 1428088 TI - Role of DNA repair in carcinogenesis. PMID- 1428089 TI - Chemicals classified by IARC: their potency in tests for carcinogenicity in rodents and their genotoxicity and acute toxicity. AB - Chemicals classified by the IARC to its groups 1, 2A, 2B and 3 were examined in an attempt to identify characteristics of their behaviour in experimental studies of carcinogenicity, genotoxicity and acute mammalian toxicity that correlate with those categories. Only those agents for which information on carcinogenic potency was available were studied. In both mice and rats, more chemicals were potent carcinogens if they had been categorized in Group 1 (human carcinogens) than if they had been put into one of the other categories. Not surprisingly, there was a weak association between carcinogenic potency and acute toxicity. Mice were especially sensitive to tumour induction by halides; the lower sensitivity of rats to any carcinogenic effect of halides could be due in part to their higher systemic toxicity in this species: a reduced differential of toxic and carcinogenic doses decreases the dose window in which carcinogenic effects may be demonstrated. It was notable that the human carcinogens were active in those genotoxicity tests with higher specificity for identifying rodent carcinogens. Predictive assays for carcinogenicity that were considered to be highly specific were tests for cytogenetic effects in vivo, unscheduled DNA synthesis in hepatocytes, mutation in any of the five commonly used strains of Salmonella typhimurium and mutation at the hprt locus in mammalian cells. None of the relationships was strong enough to form the basis of a simple categorization, but they could serve to alert investigators to chemicals of special toxicological interest and importance. PMID- 1428090 TI - Medium-term bioassays for carcinogens. AB - Medium-term bioassay systems in rats have been developed for rapid detection of carcinogenic agents and have been introduced for practical use. There are two major systems: N-nitrosodiethylamine and partial hepatectomy in liver and multiorgan models. The first model takes eight weeks; it consists of an initial intraperitoneal injection of N-nitrosodiethylamine, six weeks' administration of test chemical(s) beginning two weeks later, partial hepatectomy at week 3, and analysis of immunohistochemically identified glutathione S-transferase placental form-positive liver-cell foci. Using this model, the potency of carcinogenic agents can be predicted satisfactorily, at least for those of which the liver is a target organ. The multi-organ models include wide-spectrum organ initiation by N-methyl-N-nitrosourea or combined, short treatment with several carcinogens sequentially and subsequent administration of test chemical(s) for 12-20 weeks. Although these systems require a longer time, their accuracy as organotropism independent testing systems has been validated by whole-body histological examination. These approaches promise precise, rapid detection of carcinogenic agents and should bridge the gap between established methods for screening in vitro and long-term carcinogenicity testing, with their inherent disadvantages. Other medium-term bioassay methods are discussed in addition to our two systems. PMID- 1428091 TI - Predictive value of hepatic preneoplastic lesions as indicators of carcinogenic response. PMID- 1428092 TI - Transgenic mice in carcinogenicity testing. AB - The biological effects of the expression of single genes can be evaluated in transgenic animals. Transgenic techniques have been used to investigate a wide variety of biomedical topics, including the consequences of oncogene expression, but their use in carcinogenicity testing is just beginning. Probable future developments involving transgenic animals are new short-term assays for carcinogenicity in vivo and methods for detecting and characterizing the critical genotoxic events in carcinogenesis. PMID- 1428093 TI - Chemical toxicity and chemical carcinogenesis. Is there a causal connection? A comparative morphological evaluation of 1500 experiments. AB - Chemicals cause toxic and carcinogenic effects as well as beneficial and other adverse effects in animals and in humans. The purpose of this paper is to assess whether there is a direct, uniform causal relationship between toxicity and carcinogenicity. Within this context, specific issues receive attention: the influence of exposure concentrations on carcinogenesis; kidney cancer and alpha 2 mu-globulin; urinary calculi and tumours; and cell turnover or proliferation and cancer. The data used to evaluate histopathological site-specific correspondence between these two end-points comes from 130 studies of chemical carcinogenesis designed and conducted by the US National Toxicology Program (NTP). Nearly 1500 sex-species-exposure group experiments were evaluated for morphological evidence of toxicity and/or carcinogenicity, for dose-response relationships, and for site specific correlations of toxicity and carcinogenicity. The major conclusions are that chemicals evaluated for long-term toxicity and carcinogenicity in experimental animals can be divided into three categories: (1) those that cause organ toxicity without cancer, (2) those that cause site-specific cancer with no associated toxicity and (3) those that cause toxicity and cancer in the same organ. Examples are given to illustrate each category. On the basis of this comparative analysis, in the great majority of cases the available data do not support a correlation between chemically induced toxicity and carcinogenicity. Moreover, until considerably more scientific knowledge about molecular mechanisms of carcinogenesis becomes available and accepted, attempts to use findings on toxicity to modify the risk assessment process will be fraught with uncertainty and might even have a negative impact on public health. PMID- 1428094 TI - Species differences in carcinogen metabolism and interspecies extrapolation. AB - Many carcinogens demonstrate both qualitative and quantitative species differences in activity. Since many carcinogens must be metabolized to reactive electrophiles to elicit their tumorigenic effects, the observed species differences may have a metabolic basis. A number of examples exist that support the concept that metabolic differences are the underlying cause of species variation in carcinogenicity. Such differences are most often of a quantitative nature, but qualitative differences in carcinogenicity may also be due to differences in rates and/or pathways between species. There are also many instances in which there is no clear evidence that metabolism explains species differences in carcinogenicity. Carcinogenicity studies are often performed at much higher doses than those encountered by humans. Since metabolic processes may become saturated at high tissue concentrations, the rates and pathways of metabolic activation and detoxication may be different at high doses from those at lower doses. Such metabolic variation can lead to differences in target tissue doses, resulting in altered tissue responses at high doses in relation to lower doses. In situations in which no saturation of the metabolic pathways occurs, tissue concentrations are proportional to the administered dose. Scaling of doses from those used in experimental animals to those experienced by humans has often involved simple conversion factors, such as body weight or surface area. Since the reactions involved in carcinogen metabolism may differ both for high and low doses and for various species, much more realistic extrapolations from animal to human can be obtained using physiologically based kinetic modelling. The metabolism of carcinogens in humans shows large interindividual variation, which in turn may be reflected in differences in individual risks. The occurrence of genetic polymorphisms in carcinogen metabolizing enzymes indicates that subgroups of the population may experience carcinogenic risks distinctly different from those of the rest of the population. PMID- 1428095 TI - Significance of DNA and protein adducts. PMID- 1428096 TI - Biological markers in exposed humans: gene mutation. PMID- 1428097 TI - Human cytogenetic damage as a predictor of cancer risk. AB - The human cytogenetic assays presently available for biomonitoring are still inadequate for use in routine surveillance procedures and they must be applied with care. Knowledge of the effects of the agents concerned in experimental systems is a prerequisite, and confounding factors should be assessed. Consequently, the methods are useful and informative under carefully selected conditions and can indicate agents and exposures that are capable of causing chromosomal damage in humans, hinting at possible human cancer risk. Established and potential human carcinogens have frequently been shown to induce chromosomal aberrations in humans in vivo. It is also well documented that chromosomal rearrangements play an important role in the development of neoplasia. These combined lines of evidence suggest that structural chromosomal aberration in vivo has advantages over other cytogenetic end-points in predicting potential human cancer risk. Preliminary findings in a prospective follow-up study suggest that subjects with a high percentage of structural chromosomal aberrations but not sister chromatid exchanges may be at elevated risk for cancer. PMID- 1428098 TI - Considerations in the conduct of meta-analysis using data from animal carcinogenicity experiments. PMID- 1428099 TI - Genes and gene products that regulate proliferation and differentiation: critical targets in carcinogenesis. AB - Our understanding of the mechanism of carcinogenesis is developing rapidly, owing to the discovery of genes and gene products involved in the regulation of cell proliferation and differentiation and the identification of genetic events implicated in tumour formation. Our current concept is that cancer is basically the result of accumulating genetic damage. This damage may range from single base pair substitutions to gross chromosomal changes, leading to distortion of either the expression or the biochemical function of genes, particularly those involved in proliferation and differentiation (PDR genes). These PDR genes and gene products can now be envisioned as critical targets for interaction with carcinogens. This paper discusses only the evidence that PDR genes are critical targets for carcinogenic agents. PMID- 1428100 TI - Meta-analysis of epidemiological studies of carcinogenesis. PMID- 1428101 TI - Dose-response relationships in carcinogenesis. AB - Considerable information on the carcinogenic potential of chemical and radiological agents has accumulated from the epidemiological and toxicological studies conducted to date. In this article, we discuss dose-response relationships in carcinogenesis from both empirical and theoretical points of view. Emphasis is placed on the application of biologically based models to describe observed dose-response relationships for exposure to single and multiple agents known to increase cancer risk. The implications of these observations for inferences about possible mechanisms of carcinogenesis are explored. PMID- 1428102 TI - The role of epidemiological observation in elucidating the mechanisms of carcinogenesis. AB - Epidemiological observations concerning a number of carcinogenic agents have been used to make inferences about the biological mechanisms of carcinogenesis. These inferences have generally been based on comparisons of epidemiological data with the predictions of various mathematical models of the process of carcinogenesis. Particular interest has focused on the relationships between cancer occurrence and level of exposure, age at exposure and time since cessation of exposure, and the combined effect of two carcinogenic agents. Analyses of epidemiological data in relation to mathematical cancer models have led to conclusions about mechanisms of action, but the validity of these conclusions is necessarily limited by the nature of epidemiological data and the unverifiability of assumptions underlying the models. A more fruitful application of the epidemiological perspective in elucidating the mechanisms of carcinogenesis may be through collaborative studies involving the recently developed techniques of molecular biology and related areas. PMID- 1428103 TI - Tumour suppressor genes, multistage carcinogenesis and molecular epidemiology. PMID- 1428105 TI - Multistage and multifactorial nature of carcinogenesis. PMID- 1428104 TI - Receptor-mediated carcinogenesis. PMID- 1428106 TI - Epidemiology of cervical cancer--overview. AB - Numerous studies of the epidemiology of cervical cancer have shown strong associations with religious, marital and sexual patterns. Although it is well established that women with multiple partners and early ages at first intercourse are at high risk, less is known about how these factors interact or how risk is affected by specific sexual characteristics. Recent studies indicate that number of steady partners and frequent intercourse at early ages may further enhance risk, supporting hypotheses regarding a vulnerable period of the cervix and a need for repeated exposure to an infectious agent. It is now widely accepted that HPV is the major infectious etiological agent, but whether other infectious agents play supportive or interactive roles is unclear. Of specific interest is the independent effect of HSV 2 on risk, especially given some evidence that this viral agent may interact with HPV. Other speculative risk factors for cervical cancer include cigarette smoking, oral contraceptive usage and certain nutritional deficiencies, but again it is not clear whether these factors operate independently from HPV. Although cervical cancer incidence trends correlate with the population prevalence of various venereally transmitted agents, it is not certain how disease rates are affected by other potential risk factors which have changed during recent time (e.g., exposure to HPV, sexual behaviour, cigarette smoking). In addition, a number of recent studies highlight the need for considering not only female influences on risk of cervical cancer, but also male factors, since the sexual behaviour of the male consort appears to play an important role. PMID- 1428107 TI - Reassessment of the morphological continuum of cervical intraepithelial lesions: does it reflect different stages in the progression to cervical carcinoma? AB - Currently used histological and cytological classification systems for cervical lesions are reviewed. These suffer from poor inter- and intra-observer reproducibility, and do not allow accurate identification of which mild lesions will progress towards cancer. The Bethesda classification system is described and it is postulated that low-grade and high-grade squamous intraepithelial lesions might represent distinct entities with different potential for progression rather than necessary stages of a continuum leading to cervical cancer. Improved understanding of the etiological role of HPV types in cervical cancer and of the natural history of low- and high-grade intraepithelial lesions might result in more suitable clinical treatment of low-grade lesions. PMID- 1428108 TI - Protein kinase C of smooth muscle. AB - The primary mechanism of regulation of smooth muscle contraction involves the phosphorylation of myosin catalyzed by Ca2+/calmodulin-dependent myosin light chain kinase. However, additional mechanisms, both Ca(2+)-dependent and Ca(2+) independent, can modulate the contractile state of smooth muscle. Protein kinase C was first implicated in the regulation of smooth muscle contraction with the observation that phorbol esters induce slowly developing, sustained contractions. Protein kinase C occurs in at least four Ca(2+)-dependent (alpha, beta I, beta II, and gamma) and four Ca(2+)-independent (delta, epsilon, zeta, and eta) isoenzymes. Only the alpha, beta, epsilon, and zeta isoenzymes have been identified in smooth muscle. Both classes of isoenzymes have been implicated in the regulation of smooth muscle contraction. However, the physiologically important protein substrates of protein kinase C have not yet been identified. Specific isoenzymes may be activated by different contractile agonists, and individual isoenzymes exhibit some degree of substrate specificity. Prolonged activation of protein kinase C can result in its proteolysis to the constitutively active catalytic fragment protein kinase M, which would dissociate from the sarcolemma and phosphorylate proteins such as myosin that are inaccessible to membrane-bound protein kinase C. Protein kinase M induces relaxation of demembranated smooth muscle fibers contracted at submaximal Ca2+ concentrations. We suggest that protein kinase C plays two distinct roles in regulating smooth muscle contractility. Stimuli triggering phosphoinositide turnover or phosphatidylcholine hydrolysis induce translocation of protein kinase C (probably specific isoenzymes) to the sarcolemma, phosphorylation of protein, and a slow contraction. Prolonged association of the kinase with the membrane may lead to proteolysis and release into the cytosol of protein kinase M, resulting in myosin phosphorylation and relaxation. PMID- 1428109 TI - Blood pressure response to hyperinsulinemia in salt-sensitive and salt-resistant rats. AB - We investigated the role of insulin in salt-sensitive hypertension in Dahl salt sensitive and salt-resistant rats. The rats were kept in metabolic cages, and sodium intake and urinary sodium excretion were measured. In salt-sensitive rats receiving a 0.3% NaCl diet, sodium retention was significantly greater at weeks 1 and 2 in rats that received an insulin infusion than in those receiving a saline infusion. Mean arterial blood pressure and plasma norepinephrine levels were significantly higher at week 3 in insulin-treated rats than in saline-treated rats (mean arterial pressure, 137 +/- 3 mm Hg versus 119 +/- 3 mm Hg, p < 0.05; plasma norepinephrine, 0.40 +/- 0.02 ng/ml versus 0.27 +/- 0.01 ng/ml, p < 0.05). Insulin did not influence sodium retention, mean arterial pressure, or plasma norepinephrine in salt-resistant rats. Coadministration of an alpha-blocker (bunazosin, 10 mg/kg per day for 3 weeks) in salt-sensitive rats abolished the insulin-induced elevations in mean arterial pressure and sodium retention. When salt-sensitive rats were fed a low salt diet (0.03% NaCl), insulin did not raise mean arterial pressure. Thus, insulin elevated blood pressure only in the salt sensitive model. The sympathetic nervous system and sodium retention in the early phase of insulin overload may contribute to elevation of mean arterial pressure in this model. PMID- 1428110 TI - Relation between blood pressure and stroke mortality. AB - The relation between stroke mortality and blood pressure was investigated in 10,186 hypertensive patients followed up in the Department of Health Hypertension Care Computing Project for an average of 9 years. An untreated blood pressure measurement was available in 3,472 men and 3,405 women. The age-adjusted risk of stroke death increased by 1% for every 1 mm Hg increase in untreated systolic blood pressure. The relative hazard rate was 1.014 (95% confidence interval [CI], 1.007, 1.021) in men and 1.009 (1.003, 1.016) in women. The corresponding increases for 1 mm Hg for untreated diastolic blood pressure were almost 3% in men and again 1% in women (relative hazard rate 1.026 [95% CI, 1.014, 1.038] in men and 1.010 [1.000, 1.021] in women). Treated blood pressure measurements were available in 3,073 men and 3,148 women. Stroke mortality increased by 2% for a 1 mm Hg increase in treated systolic pressure and 3% for the corresponding increase in diastolic blood pressure. The relation between stroke mortality and blood pressure was similar over and under the age of 65, although the increase in mortality with pressure was greater for treated diastolic blood pressure in women under the age of 65 than over this age. There was no evidence for a J-shaped relation between stroke mortality and either systolic or diastolic pressure in men. In women there was a suggestion of such a relation, but since this relation was also observed for untreated pressures, any increase in risk at lower pressures is unlikely to be a result of treatment. PMID- 1428111 TI - Increased response to physical and mental stress in men with hypertensive parents. AB - Blood pressure and heart rate responses to isometric handgrip exercise were studied at age 31 and after 5 years in young nonhypertensive men with positive family histories of hypertension (n = 13) and in those with negative family histories of hypertension (n = 13) for two generations to test whether subjects with positive family histories established a pattern of increased blood pressure and heart rate responses during the 5-year follow-up period. At follow-up the response to mental stress (Stroop's color word test) was also studied. Baseline blood pressure and heart rate at rest did not differ, initially or at follow-up, between the groups. At the initial examination, absolute blood pressure levels were significantly higher during isometric handgrip exercise just before exhaustion in subjects with positive family histories. At follow-up the absolute blood pressure level (p < 0.001) and the blood pressure responses (p < 0.01 0.001) were found to be significantly increased during handgrip exercise in subjects with positive family histories compared with subjects with negative family histories. In subjects with positive family histories the diastolic blood pressure response was significantly higher (p < 0.01) at follow-up than initially and was significantly related (r = 0.70, p < 0.01) to changes in baseline diastolic blood pressure during the follow-up period. In subjects with negative family histories the systolic blood pressure response was somewhat lower at follow-up than initially. During the mental stress test, the blood pressure response was significantly greater in subjects with positive than with negative family histories.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428112 TI - Sympathetic denervation blocks blood pressure elevation in episodic hypoxia. AB - We have previously described a rat model that responds to repetitive episodic hypoxia (FiO2 nadir 3-5% for 12 seconds every 30 seconds for 7 hr/day for 35 days) with chronic increase in arterial blood pressure. The purpose of the current study was to determine if peripheral sympathetic nervous system denervation blocks this persistent blood pressure elevation. Chemical sympathetic denervation was achieved and maintained by three intraperitoneal injections (100 mg/kg 6-hydroxydopamine) on days 1, 3, and 27 of a 47-day experiment in two groups of rats. One denervated group was subjected to episodic hypoxia for 40 consecutive days beginning on day 7 and the other remained unhandled in their usual cages. A third group was injected with vehicle only and subjected to the same episodic hypoxia while a fourth group remained unhandled for 40 days. The vehicle-treated, episodic hypoxia-exposed group showed a 7.7 mm Hg increase in mean arterial blood pressure (conscious, unrestrained) over the 40-day period, whereas all other groups showed a decrease in mean arterial pressure. The left ventricle and septum/whole body weight ratio was higher in both episodic hypoxia exposed groups at the end of the study. Plasma epinephrine in both groups administered 6-hydroxydopamine was higher on day 6 than in the vehicle-injected rats. Measurement of catecholamines in cardiac muscle homogenate confirmed denervation in 6-hydroxydopamine animals. These results indicate that the peripheral sympathetic nervous system is necessary for the persistent increase in blood pressure in response to repetitive episodic hypoxia. PMID- 1428113 TI - Hypocalcemia and pregnancy-induced hypertension produced by maternal fasting. AB - During pregnancy, maternal calcium needs increase as a result of increasing calcium requirements for fetal bone development. These needs have to be completely supplied by the mother via placental transfer. Several studies link low serum ionized calcium concentrations with the development of hypertension and pregnancy-induced hypertension. We hypothesized that maternal hypocalcemia would develop concomitantly with the development of hypertension in sheep that were fasted in late gestation. Sixteen instrumented ewes were used in the present study. After a 2-day baseline period, food was withdrawn from 10 animals in the experimental group (group 2) for 3 days, whereas the remaining six were allowed to eat and drink normally (group 1). Blood pressure, uteroplacental blood flow, and heart rate were monitored daily. Fasted animals were given deionized water (calcium free) to drink, whereas control animals were given tap water containing 32.9 mg/l calcium concentration. Based on the analysis of the ionized calcium concentration response to fasting, group 2 animals were placed in one of two groups: hypocalcemia did not develop in group 2a, whereas in group 2b the ionized calcium concentration decreased 27% (from 1.09 +/- 0.07 to 0.80 +/- 0.06 mM, p = 0.01) by the third day of fasting. Group 2b responded with a 16% elevation in maternal blood pressure (p = 0.01) and a 43% reduction in uteroplacental blood flow. Furthermore, a positive correlation was found between maternal and fetal blood ionized calcium concentrations (r = 0.860).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428114 TI - Increased platelet angiotensin II receptor number in pregnancy-induced hypertension. AB - Women with pregnancy-induced hypertension (PIH) are characterized by relatively greater blood pressure sensitivity to exogenous angiotensin II (Ang II) than normotensive pregnant women. Evidence suggests that this is due to an alteration in Ang II receptor sites. However, the question of whether this represents an increase in receptor number or affinity remains unanswered. To answer this question Ang II receptors on platelets from normotensive women during each trimester of pregnancy and the postpartum period were studied and compared with platelet Ang II binding in third trimester women with PIH and in postpartum women who had had a recent pregnancy complicated by PIH. We also measured plasma renin activity, Ang II, and aldosterone in blood samples from these women and sodium and creatinine in 24-hour urine collections. Normotensive pregnant women had significantly less platelet Ang II binding than nonpregnant, postpartum women (0.85 +/- 0.19 versus 2.87 +/- 0.83%, p = 0.003), reflecting a reduction in receptor number but not affinity. This probably reflects the significant increase in Ang II during pregnancy. Urinary sodium excretion was equivalent and could not explain these changes. Comparisons of third trimester women with PIH against those without PIH documented a significantly higher Ang II binding in the women with PIH (2.23 +/- 0.42 versus 0.85 +/- 0.19%) that was caused by an increase in receptor number (6.0 +/- 1.3 versus 3.0 +/- 0.8 fmol Ang II per 5.6 x 10(8) platelets, p = 0.047) but similar Ang II binding affinity. This reflected significantly lower Ang II levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428115 TI - Angiotensin II-induced protein phosphorylation in the hypertrophic heart of the Dahl rat. AB - Angiotensin II-induced phosphorylation of proteins was examined in isolated myocytes from hearts of Dahl rats. A high salt diet induced cardiac hypertrophy in Dahl salt-sensitive rats. Angiotensin II-induced phosphorylation of a 42-kd protein (pp42) was detected by two-dimensional electrophoresis in hypertrophic but not normal ventricular myocytes. Angiotensin II stimulation was time dependent, with a peak effect at 30 minutes. The half-maximal and maximal concentrations of angiotensin II that stimulated pp42 phosphorylation were 1 and 10 nM, respectively. Phosphorylation of pp42 was a function of cardiac hypertrophy. Phorbol 12-myristate 13-acetate-induced phosphorylation of pp42 indicates the possibility of an association between protein kinase C and the signal transduction pathway of angiotensin II-induced pp42 phosphorylation. Ionomycin and A23187 (both at 1 microM) did not stimulate phosphorylation of pp42. Angiotensin II produced a small increase in the synthesis of myocyte proteins in both normal and hypertrophic cells as shown by [35S]methionine incorporation. However, this increase could not account for the increase in the phosphate content of pp42. This protein was not an isoform of actin nor was it of platelet origin. These results raise the possibility that angiotensin II may play a role in the activation of factors in hypertrophic myocytes; however, further study is required to define a link between phosphorylation of pp42 and the hypertrophic process. PMID- 1428116 TI - Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. AB - Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake. PMID- 1428117 TI - Alterations in renal endothelin-1 production in the spontaneously hypertensive rat. AB - Endothelin-1 inhibits sodium and water transport systems in the inner medullary collecting duct. Endothelin-1 levels are reduced in the medulla of spontaneously hypertensive rats (SHR), raising the possibility that decreased inner medullary collecting duct production of endothelin-1 could contribute to inappropriate sodium and water retention. In the current study, immunoreactive endothelin-1 was measured in the urine, blood, and eluates from cortex and outer and inner medulla of SHR before (age 3-4 weeks) and after (age 8-9 weeks) the development of hypertension and in age-matched Wistar-Kyoto (WKY) controls. There was no difference in endothelin-1 levels between prehypertensive SHR and WKY rats. In contrast, 8-9-week-old SHR had significantly reduced endothelin-1 in the urine and outer and inner medulla, but not in the cortex or serum compared with those of WKY controls. Furthermore, inner medullary collecting duct cells from 8-9-week old SHR, either acutely isolated or cultured, released less endothelin-1 than did those from WKY rats. Finally, the level of endothelin-1 messenger RNA was only reduced in the inner medulla and in inner medullary collecting duct cells from 8 9-week-old SHR. In summary, renal medullary, and in particular terminal collecting duct, endothelin-1 production is reduced in SHR only after the development of hypertension. Such decreases in inner medullary collecting duct endothelin-1 production may contribute to the hypertensive state in SHR. PMID- 1428118 TI - Effects of antihypertensive agents on arterial baroreceptor reflexes in conscious rats. AB - The effects of antihypertensive treatment with four currently used agents (trichlormethiazide, atenolol, nicardipine, and enalapril) on the arterial baroreceptor reflex control of renal sympathetic nerve activity and heart rate were investigated in 45 conscious spontaneously hypertensive rats and 37 age matched Wistar-Kyoto rats. Antihypertensive agents were administered for 2 weeks beginning at 8 weeks of age to treat and prevent the development of hypertension. Blood pressure was reduced to a similar level (-13 +/- 3 mm Hg, p < 0.05) by each antihypertensive agent. Blood pressure, heart rate, and renal sympathetic nerve activity were recorded in the conscious state during phenylephrine and nitroglycerin ramp infusion. The gain in the baroreceptor reflex was determined from the maximum slope of logistic function curves. Untreated spontaneously hypertensive rats exhibited decreased sensitivity of reflex control of renal sympathetic nerve activity and heart rate (-1.78 +/- 0.07% of control/mm Hg and 2.16 +/- 0.05 beats per minute/mm Hg, respectively) compared with untreated Wistar-Kyoto rats (-3.62 +/- 0.18% of control/mm Hg, p < 0.01, and -3.46 +/- 0.11 beats per minute/mm Hg, p < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428119 TI - Hypertension and histocompatibility antigens. PMID- 1428121 TI - Enzymatic activity and immunoreactivity of extracellular phospholipase A2 in inflammatory synovial fluids. AB - Synovial fluid PLA2 concentration was measured by an ELISA technique using monoclonal antibodies raised against human recombinant "synovial-type" group II phospholipase A2. This ELISA was specific for synovial-type PLA2 and did not detect pancreatic (group I) PLA2. In all synovial fluids examined, including rheumatoid, osteoarthritic, psoriatic, and gouty fluids, synovial fluid PLA2 enzyme activity significantly correlated with PLA2 immunoreactivity (P < 0.001). Within the limits of the ELISA technique, there was no evidence for the presence of specific or nonspecific modulation of PLA2 activity by either putative PLA2 activating or inhibitory proteins. PMID- 1428122 TI - Concentration and turnover of intraperitoneal hyaluronan during inflammation. AB - Aseptic peritonitis was induced in rabbits by intraperitoneal injection of irritating agents, mainly starch suspensions. The inflammatory response was followed in the peritoneal lavage fluid by cell counts (average increase about 800-fold the first day) and hyaluronan concentration (average increase about 200 fold on the second and third days). The turnover rate of hyaluronan was studied by injecting tritium-labeled hyaluronan intraperitoneally and by following the appearance of tritiated water in serum. In control animals given trace amounts of hyaluronan, half-lives of 1-14 h were recorded. When the labeled polysaccharide had been mixed with 10 mg/ml of unlabeled hyaluronan, the half-life was approximately one day. Rabbits with ongoing peritonitis exhibited half-lives between 1 and 16 h. It was concluded that there was a large individual variation in uptake kinetics, that the removal process could be receptor mediated, and that the increase in intraperitoneal hyaluronan in peritonitis mainly was due to an increased production of the polysaccharide rather than a decreased rate of removal. PMID- 1428120 TI - Molecular mechanism of methotrexate action in inflammation. PMID- 1428123 TI - Bone-resorbing activity is expressed by rat macrophages in response to arthropathic streptococcal cell wall polymers. AB - Rat peritoneal macrophages stimulated in vivo by group A streptococcal peptidoglycan-polysaccharide (PG-APS) resorb bone as measured by solubilization of 45Ca from radiolabeled, devitalized bone chips. Activity was strain-dependent and correlated with the susceptibility of rat strains to PG-APS-induced arthritis. PG-APS-stimulated macrophages from the resistant Buf rat strain were not induced to resorb bone, but ingested equivalent concentrations of PG-APS compared to bone-resorbing macrophages from the arthritis-susceptible Lew strain. Resorptive activity peaked at three to five days and decreased to background levels by 10 days after injection. PG-APS-stimulated macrophages from congenitally athymic Lew rats were as effective as macrophages from heterozygous littermates at resorbing bone. Lew macrophages were also responsive to small, nonarthropathic PG-APS polymers generated by mutanolysin digestion. Resident peritoneal macrophages did not respond to stimulation by PG-APS in vitro. Indomethacin at a concentration of 10 micrograms/ml was an effective blockade against PG-APS-induced macrophage bone resorption in vitro, but catalase was ineffective. These results indicate that expression of rat macrophage bone resorbing activity reflects genetic regulation of the response to PG-APS rather than a defect in ingestion of these polymers and imply that PG-APS-stimulated, bone-resorbing macrophages may contribute to early, initial bone destruction that occurs in inflammatory arthritis. PMID- 1428124 TI - Inhibition of prekallikrein activation in human plasma by components of bovine plasma. AB - Contact of plasma with a negatively charged surface activates prekallikrein and factor XII reciprocally. Activation of prekallikrein by several activators was impaired in bovine plasma when compared to that in human plasma. The activated partial thromboplastin time of bovine plasma, induced by several activators, was significantly longer than that of human plasma. Cleavage of [125I]factor XII was optimum at 10 min in human plasma but took up to 60 min in bovine plasma. Addition of bovine plasma to human plasma caused significant inhibition of dextran sulfate-induced prekallikrein activation, indicating that the impaired rate of contact activation in bovine plasma is due to the presence of inhibitors. The inhibitory effect was greater at lower concentrations of dextran sulfate but could not be abolished by increasing the concentration. The inhibitory activity eluted in two peaks at low and medium salt concentrations on carboxymethyl ion exchange chromatography of bovine plasma. PMID- 1428125 TI - Neuropeptides in pulmonary edema fluid of adult respiratory distress syndrome. AB - A role for peptidergic nerves in the adult respiratory distress syndrome (ARDS) was examined by radioimmunochemically quantifying neuropeptides in pulmonary edema (PE) fluids from seven patients with ARDS and six patients with PE from congestive heart failure (CHF). The PE fluid mean concentrations of substance P (SP) and gastrin-releasing peptide (GRP) were significantly higher in ARDS (0.59 +/- 0.29 SD and 0.10 +/- 0.03 nM, respectively, P < 0.001 for both) than in CHF (0.19 +/- 0.08 and 0.04 +/- 0.01), whereas no difference was detected between the mean levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the two forms of PE. Mean alveolar fluid concentration of SP was 8.7 nM (range 2.1-20.5 nM, N = 4) in sheep with acute lung injury from intravenous Pseudomonas aeruginosa, but was undetectable in sheep with balloon induced high left atrial pressure simulating CHF (N = 2) or control sheep (N = 2). Pulmonary lymphatic clearance of SP, which reflected the rate of generation of SP in the lungs, attained a maximum of 25-95 pmol/h in sheep given P. aeruginosa intravenously, but was detected in only one of four control sheep at a lower level. Some pulmonary neuropeptides thus are released locally by acute lung injury and may contribute to endothelial and/or epithelial abnormalities underlying the altered capillary-alveolar permeability in ARDS. PMID- 1428128 TI - It is time we thought of youth. PMID- 1428129 TI - Growth hormone therapy: current status. PMID- 1428130 TI - Congenital factor XIII deficiency. AB - Clinical and hematological data of 9 cases with factor XIII deficiency is highlighted. The age at first bleed ranged from 3 days of life to 1 year. Seven of these 9 cases had bleeding from the umbilicus, 3 had recurrent subcutaneous and muscle hematomas, while 4 cases had CNS bleeds of which 3 expired. Routine coagulogram was normal, while clot solubility in 5 molar urea solution was abnormal in all cases. Factor XIII assay was not done in any. Patients were treated with plasma transfusion during episodes of bleeding. No patient received plasma transfusion as prophylactic therapy. The cumulative Indian data so far documented, inclusive of this series, shows a very high incidence of CNS bleeds (33%) in patients with this inherited coagulation disorder. PMID- 1428127 TI - Hyperphospholipasemia A2 in human volunteers challenged with intravenous endotoxin. AB - Phospholipase A2 (PLA2) activity was measured in the serum of 23 individuals infused intravenously with endotoxin (EN) at a dose of 4 ng/kg body weight. A marked increase in PLA2 was noted 3 h after EN challenge (mean 828 +/- 513 units/ml), reached its maximum at 24 h after the challenge (mean 2667 +/- 2442 units/ml), and was still evident at 48 h (mean 763 +/- 366 units/ml). In contrast, TNF levels were maximal (mean 712 +/- 375 pg/ml) 90 min after the EN challenge and subsided to very low values (5 +/- 5 pg/ml) 5 h after the challenge. There was a positive correlation between the maximum response of TNF and that of PLA2 (r = 0.82, P < 0.01). Administration of ibuprofen or pentoxifylline did not alter the PLA2 response. EN challenge did not affect serum pancreatic PLA2 concentration or that of the lysosomal cationic enzyme, lysozyme. Neutralizing antibody against human recombinant (synovial type) PLA2 completely abolished PLA2 activity in the sera tested. We conclude that EN infusions cause marked intravascular release of nonpancreatic secretory PLA2 and that the magnitude of this response seems to be related to the prior generation of TNF. PMID- 1428126 TI - Synergism among oxidants, proteinases, phospholipases, microbial hemolysins, cationic proteins, and cytokines. AB - A striking similarity exists between the pathogenetic properties of group A streptococci and those of activated mammalian professional phagocytes (neutrophils, macrophages). Both types of cells are endowed by the ability to adhere to target cells; to elaborate oxidants, hydrolases, and membrane-active agents (hemolysins, phospholipases); and to freely invade tissues and destroy cells. From the evolutionary point of view, streptococci might justifiably be considered the forefathers of "modern" leukocytes. Our earlier findings that synergy between a streptococcal hemolysin (streptolysin S, SLS) and a streptococcal thiol-dependent proteinase and between cytotoxic antibodies+complement and streptokinase-activated plasmin readily killed tumor cells, led us to hypothesize that by analogy to the pathogenetic mechanisms of streptococci, the mechanisms of tissue destruction initiated by activated leukocytes in inflammatory sites, as well as in tissues undergoing episodes of ischemia and reperfusion, might also be the result of the synergistic effects among leukocyte-derived oxidants, phospholipases, proteinases, cytokines, and cationic proteins. The current report extends our previous synergy studies with endothelial cells to two additional cell types--monkey kidney epithelial cells and rat beating heart cells. Monolayers of 51Cr-labeled cells that had been treated by combinations of sublytic amounts of hydrogen peroxide (generated either by glucose oxidase, xanthine-xanthine oxidase, or by paraquat) and with sublytic amounts of a variety of membrane-active agents (streptolysin S, phospholipases A2 and C, lysophosphatides, histone, chlorhexidine) were killed in a synergistic manner (double synergy). Crystalline trypsin markedly enhanced cell killing by combinations of oxidant and the membrane-active agents (triple synergy). Injury to the cells was characterized by the appearance of large membrane blebs that detached from the cells and floated freely in the media, looking like lipid droplets. Cytotoxicity induced by the various combinations of agonists was depressed, to a large extent, by scavengers of hydrogen peroxide (catalase, dimethyl thiourea, and by Mn2+) but not by SOD or by deferoxamine. When cationic agents were employed together with hydrogen peroxide, polyanions (heparin, polyanethole sulfonate) were also found to inhibit cell killing. It is proposed that in order to effectively combat the deleterious toxic effects of leukocyte-derived agonists on cells and tissues, antagonistic "cocktails" comprised of cationized catalase, cationized SOD, dimethylthiourea, Mn(2+)+glycine, proteinase inhibitors, putative inhibitors of phospholipases, and polyanions might be concocted. The current literature on synergistic phenomena pertaining to mechanisms of cell and tissue injury in inflammation is selectively reviewed. PMID- 1428131 TI - Glanzmann's thrombasthenia. AB - During January 1981 to June 1991, 20 patients from 16 unrelated families were detected to have Glanzmann's thrombasthenia (GT). Twelve families (75%) had history of consanguinity, with 6 first cousins and 3 uncle-niece marriages; of these 7 were Muslims, 6 Hindus and 3 Christians. There were 12 girls and 8 boys; the mean age at diagnosis was 7.05 +/- 6.03 yr (range 1 day-22 yr). All cases had initial bleeding prior to the age of 5 yr with the mean age at the initial episode of bleeding being 2.21 +/- 1.34 yr (range 1 day-5 yr). Common pattern of bleeding included epistaxis, gingival bleeding, post-traumatic bruises, menorrhagia, gastrointestinal (2 cases), post-operative (2 cases) and spontaneous bleeding (2 cases). No patient showed hemarthrosis, intracranial bleeding or hemoptysis. Menorrhagia was a serious problem necessitating repeated transfusions and hormonal therapy. Twelve cases (60%) required 1-120 units of blood transfusions while five received platelet concentrates. PMID- 1428132 TI - Efficacy of intrathecal methotrexate with and without cranial radiotherapy in preventing central nervous system relapses in acute lymphocytic leukemia. AB - Introduction of CNS chemoprophylaxis was a major milestone in the development of current therapy for acute lymphocytic leukemia. However, controversies are still existing for ideal form of CNS chemoprophylaxis. The present study was conducted to determine the efficacy of intrathecal methotrexate (IT-MTX) with and without cranial radiotherapy in preventing CNS relapses in Indian children. CNS chemoprophylaxis comprising of six injections of intrathecal methotrexate (12 mg/M2) was administered alone or along with cranial radiotherapy (2000 GY) in 76 children each after successful induction remission. Cranial radiotherapy (RT) with intrathecal methotrexate (IT-MTX) was observed to be more effective as CNS relapses were seen in 11.8% of children as compared to 16.8% of children receiving IT-MTX alone. IT-MTX along with cranial RT delayed the occurrence of CNS relapses and prolonged the event free survival periods. PMID- 1428133 TI - Diagnostic and prognostic value of bromide partition test in tuberculous meningitis. AB - Bromide partition ratio was determined in 32 cases of tuberculous meningitis, 6 pyogenic meningitis, 8 viral meningitis and 9 cases of febrile convulsions. Bromide partition ratio below the critical value of 1.6 was present in 30 out of 32 tuberculous meningitis patients (93.74%) whereas all the control children had a ratio above 1.6. Two children who were on regular chemotherapy showed progressively rising ratio. It is concluded that in doubtful cases with inconclusive CSF picture, a low bromide partition ratio is a strong reason for starting antituberculous treatment without any delay. A very low ratio also suggests poor prognosis. PMID- 1428134 TI - Comparative study of oral versus injectable vitamin K in neonates. AB - One hundred term exclusively breast fed babies weighing more than 2.5 kg were evaluated to determine the efficacy of various modes and doses of Vitamin K to prevent hemorrhagic disease of newborn (HDN). The babies were grouped into four categories of 25 each: Group A--1 mg Vitamin K intramuscular (Menadione sodium disulphite) at birth; Group B--0.5 mg Vitamin K intramuscular; Group C--1 mg Vitamin K orally, and group D--no Vitamin K. The prothrombin index was estimated in all babies between 36-72 hours of age. The results revealed a prothrombin index in Groups A, B, C and D as 94.98 +/- 7.64%, 95.08 +/- 9.91%, 92.51 +/- 10.10% and 80.39 +/- 15.90%, respectively. The differences between Groups A, B and C were insignificant. However, Group D, prothrombin index was significantly reduced as compared with the other three groups. It is, therefore, concluded that oral Vitamin K is as effective as injectable Vitamin K and its usage is recommended in our country to reduce complications and costs of parenteral therapy. PMID- 1428135 TI - Bronchial challenge with purified protein derivative of Mycobacterium tuberculosis in asthma. AB - Response to bronchial challenge (BC) with purified protein derivative of Mycobacterium tuberculosis (PPD), was studied in children with bronchial asthma and correlated with Mantoux test and serum immunoglobulin E (IgE) against PPD (PPD-Sp IgE). Nearly 59% patients with bronchial asthma and 12.2% patients with pulmonary tuberculosis gave positive BC. Children with extra-pulmonary tuberculosis and normal children did not show positive BC. In asthma, 25% gave early (EAR), 50% gave late (LAR) and 25% gave both early and late (DAR) asthmatic response. Forced expiratory flow volumes in 1 sec (FEV.1) of 13 age and sex matched asthmatic and normal children showed similar volumes before BC, however, the values were significantly lower in asthma at 20 min (p less than 0.005) and 24 h (p less than 0.005) after BC. There was no relationship between response to BC and the severity or chronicity of asthma. PPD-Sp IgE was estimated by the radioimmunoassay method (Pharmacia Diagnostics). It was detected in 75% with positive BC and none of the controls. The titre was of Phadebas RAST Class III in 66.7%, Class II in 22.2% and Class I in 11.1%. The presence of early Mantoux reactions, positive BC with PPD and serum PPD-Sp IgE suggest the existence of Type I or Arthus type of reactions to PPD, which could cause hyperreactive airways in some cases of asthma. PMID- 1428136 TI - Chest radiographs in neonatal septicemia. AB - Chest radiographs of 63 culture proven cases of neonatal septicemia were evaluated in this prospective study. Gram negative septicemia was responsible for 76.2% cases. Radiological abnormalities were observed in 27 cases (42.8%). Seven of these had no respiratory distress. The findings were right sided infiltrates (27%); hyperinflation (7.9%), bronchopneumonia (6.3%) and pneumothorax (1.6%). Increasing gestational age, late onset of illness (greater than 3 days) and presence of respiratory signs of distress had a positive correlation with presence of X-ray findings. Term newborns with respiratory distress of late onset sepsis (greater than 3 days) had significantly higher number (p less than 0.05) of abnormal radiographs. Presence of radiological abnormality neither influenced the clinical outcome nor was affected by the causative organisms. The practice of doing a chest radiograph routinely in cases of neonatal septicemia is justified irrespective of presence of respiratory signs of distress. PMID- 1428137 TI - Participation of health workers, school teachers and pupils in the control of rheumatic fever: evaluation of a training programme. AB - In a rural community block of north India we initiated a programme for control of rheumatic fever and rheumatic heart disease (RF/RHD). This included a training campaign for all 74 health workers, 773 school teachers and 12,500 older pupils (class V to X) to enable them to suspect and refer cases of RF/RHD and counsel them about secondary prophylaxis. Training material was used by project staff, medical officers and teachers to convey that this serious disease with onset between 5 and 15 years can be recognized by four simple criteria: fever with joint pain or swelling; breathlessness and fatigue; involuntary face and limb movements. One year later we evaluated awareness generated by training by administering a questionnaire to random samples in the intervention area and in a noncontiguous control area. Health workers, teachers and pupils of the intervention block were significantly better aware of the nature, severity and presentation of the disease and reported having recognized cases whom they had referred for diagnosis, prophylaxis and counselled for follow up. We conclude that a training protocol incorporating simple messages can effectively create practical awareness for RF/RHD control among teachers, health workers and pupils in a rural community. PMID- 1428138 TI - Experience with a measles vaccine manufactured in India. AB - Five hundred and twenty seven children between 7 months and 2 years of age were vaccinated with measles vaccine manufactured by the Serum Institute of India. The sero-conversion rate in children who had no antibodies previous to vaccination was 98.4% as tested in HI. Ninety per cent of children who had pre-vaccination measles antibodies showed a two-fold or more rise in HI antibodies. The side reactions of the vaccine were negligible. PMID- 1428139 TI - Recommendations for creation of modest level II neonatal care facilities in India. PMID- 1428140 TI - Double heterozygosity for hemoglobin S and E. PMID- 1428141 TI - Hemophagocytic syndrome. PMID- 1428142 TI - Salmonella typhi meningitis with facial nerve palsy. PMID- 1428143 TI - Potassium cyanide poisoning. PMID- 1428144 TI - Salmonella typhi meningitis. PMID- 1428145 TI - Prescribing habits of pediatricians for gastroenteritis. PMID- 1428146 TI - Myelofibrosis. PMID- 1428147 TI - Knowledge and practices regarding diarrhea in rural mothers of Haryana. PMID- 1428149 TI - Hallermann-Streiff syndrome. PMID- 1428148 TI - Values for total hand length, palm length and middle finger length in newborns from 26-42 weeks gestation. PMID- 1428150 TI - Spondylocostal dysplasia. PMID- 1428151 TI - Benign cystic teratoma of the mediastinum. PMID- 1428152 TI - Wilson's disease: initial worsening of neurologic syndrome with penicillamine therapy. PMID- 1428154 TI - Ocular complications following mumps. PMID- 1428153 TI - Inherited deletion of chromosome (21p-) in a child with congenital malformation and psychomotor retardation. PMID- 1428155 TI - Wolman disease: suggestions for effective treatment. PMID- 1428156 TI - Chloramphenicol resistant S. typhi. PMID- 1428157 TI - Coin gift: a potentially fatal custom. PMID- 1428158 TI - Investigative approach and medical management or portal hypertension. PMID- 1428159 TI - Eight years' experience of clinical activity in an outpatient fracture clinic. AB - Major changes to the method of planning and provision of health care in Britain have led to the introduction of contracts as the main means through which services are procured. Never before has the need for accurate and comprehensive clinical information been greater. Yet comprehensive outpatient information, though planned, is not yet available, and there is relatively little experience of such systems which have been introduced in individual localities. Fracture clinic patients are an important group of outpatient, not least because interventions are often undertaken as an integral part of the outpatient episode. This is relevant for estimating resource use and for pricing, but until now has been 'hidden' work as far as conventional information systems are concerned. This study describes the establishment and manifestation of a clinical information system based on a fracture clinic serving the majority of a population of 850,000. Information was gathered over 8 years on 61,635 patients, who had 72,984 diagnoses and received 93,878 treatments. An information system of the type described in this study can be of great value as part of the contracting process (for both purchasers and providers of orthopaedic services), as a basis for clinical audit and research, and to facilitate undergraduate and postgraduate teaching. PMID- 1428160 TI - Iselin's operative technique for thumb proximal metacarpal fractures. AB - Between 1980 and 1989, 33 patients were treated operatively according to Iselin for a proximal metacarpal thumb fracture. At follow-up all but one patient had a good functional result with no restrictions in work, sports, or delicate hand movements. PMID- 1428161 TI - Primary external fixation and secondary intramedullary nailing in the treatment of tibial fractures. AB - The results of primary external fixation and secondary intramedullary nailing of 21 tibial fractures are presented. It is shown that if secondary nailing is delayed until after granulation of the pin sites the technique is associated with a low infection rate. The union time for tibial fractures compares well with that of external fixation, although in closed and Gustilo type I open fractures primary intramedullary nailing gives superior results. PMID- 1428162 TI - Role of prophylactic antibiotics in open and basilar fractures of the skull: a randomized study. AB - The aim of this study was to investigate the controversial issue of the use of prophylactic antibiotics in open and basilar fractures of the skull. A series of 157 patients were randomized to receive no antibiotics (group A = 46 patients) or ceftriaxone for 3 days (group B = 50 patients), or the combination ampicillin/sulphadiazine for 3 days (group C = 61 patients). The incidence of meningitis was similar in both the antibiotic and non-antibiotic groups. However, the overall incidence of infectious complications in the non-antibiotic group was significantly higher than in the antibiotic group (8.7 per cent vs 0.9 per cent, P < 0.05). There was no significant difference between the ceftriaxone group and the ampicillin/sulphadiazine group. The results of the study suggest that antibiotic prophylaxis has a role in the management of open and basilar fractures. PMID- 1428163 TI - Interlocking nailing for fractures of the femur and tibia. AB - In 132 patients, fractures of the lower limb (71 femoral and 61 tibial fractures) were treated using interlocking nailing (ILN) according to Grosse and Kempf during the period 1986-1989. Of these, 118 were followed up for a median of 19 months (range 9-32 months). Inpatient stay averaged 9 days regardless of the fracture. Consolidation was achieved in approximately 3 or 4 months from the operation in tibial and femoral fractures, respectively. Tibial fractures were technically more demanding than femoral ones, and their average operating time was significantly longer (73 min versus 51 min). Only one patient had a malunion in malrotation. The most serious complication was in a closed upper tibial fracture with traumatic rupture of the popliteal artery. Although the nailing was technically successful, an above-knee amputation had to be carried out. In only one case did the nail fail, and tibial plating had to be performed. Given the present degree of expertise, ILN for fractures of the long bones of the lower limb is a safe and relatively easy procedure to perform. PMID- 1428164 TI - Percutaneous screw fixation of tibial plateau fractures. AB - A series of 13 patients with displaced fractures of the tibial plateau treated by closed reduction and percutaneous pinning have been reviewed 17 months after surgery. All the operations were performed using image intensification to aid reduction of the fracture by ligamentotaxis and to guide screw placement. In two cases, arthroscopy was used in addition to facilitate elevation of the articular surface using a probe inserted through a cortical window in the proximal tibial metaphysis. The postoperative rehabilitation programme consisted of early mobilization and non-weight bearing for at least 2 months. Of the patients, 11 had a satisfactory result, one patient had a fair result with persistent pain and the other had a poor result when the fixation failed in a comminuted bicondylar fracture in porotic bone. This technique is minimally invasive and avoids many of the complications of both conservative and operative treatment and will have an expanding role to play in the management of these fractures. PMID- 1428165 TI - Post-traumatic abdominal mucormycosis. AB - Gastrointestinal mucormycosis, an opportunistic fungal infection, is a rare complication of trauma. We report on four patients who developed this frequently fatal condition after delayed treatment of intra-abdominal sepsis and discuss the aetiology, diagnosis and management of the disease. PMID- 1428167 TI - Injuries to the spinal cord in elderly patients. AB - There are certain differences between the mechanism of injury and the course and results of treatment of post-traumatic spinal cord injuries in younger and older victims. Between 1965 and 1990 there were 564 patients over 60 years of age with spinal cord or cauda equina injuries treated at the Spinal Cord Centre in Konstancin, Poland. This article presents the level and degree of the nervous system injury, the methods of treatment and early mortality in the series. Of the patients, 43 per cent were aged between 60 and 65 years, but 31 per cent were patients over 70 years of age. More patients sustained injury to the cervical spine (72 per cent), and 42 per cent of lesions to the spinal cord were neurologically assessed as complete transverse cases. This paper stresses the high mortality rate, amounting to 26 per cent overall and 48 per cent in the groups with complete spinal cord lesions. PMID- 1428166 TI - Trauma deaths in the south west Thames region. AB - This is an epidemiological study based on Coroners' records analysing mode of injury and place and cause of death. The aim of the study is to provide data on the incidence and patterns of death from trauma and to assess the need for changes in trauma management. All traumatic deaths occurring in the South West Thames Region during 1988 were studied. We analysed 434 of these deaths (mean age 52 years) in some detail. Of the deaths, 59 per cent occurred before arrival at hospital. Road traffic accidents are the commonest cause of death from trauma, being most prevalent in the areas containing major trunk roads. The majority of deaths due to chest injury (79 per cent) and multiple injuries (70 per cent) occurred before arrival at a hospital, whereas the majority of deaths due to head injury (63 per cent) occurred after admission. The majority of deaths from trauma occur before arrival at a hospital, particularly in the semi-rural areas. Improvements in hospital trauma care could have only a limited effect on the death rate in existing circumstances. If important reductions in deaths from severe injury are to be made then prevention and prehospital care need to be improved. PMID- 1428168 TI - Surgery in Afghanistan: a light model for field surgery during war. AB - Owing to a poor capability for evacuation, mobile medical teams were sent to the area of Gazni in Afghanistan to work with local paramedics as part of a medical programme for the area. The teams were equipped to perform major surgery. During 1 month a surgical team inside Afghanistan performed 53 operations. The operations were performed in the patients' homes at night. The team had to move frequently so as not to be spotted by the Soviet and government surveillance. Equipment equivalent to a light field hospital was stored in a safe place and the team carried supplies for 1 or 2 days on their bicycles. One postoperative death and one wound infection were recorded. It is concluded that adequate surgery can be performed inside territories where enemy forces have air control and under primitive conditions with an acceptable rate of complications. However, due to the nature of the guerrilla warfare with scattered military confrontations over vast areas, the average time between injury and treatment for war casualties was 36 h. PMID- 1428169 TI - Surgery in a Palestinian refugee camp. AB - From 1985 to 1987, three Palestinian refugee camps in Lebanon were attacked several times by a Lebanese militia. We present a review of 1276 casualties who were wounded in the refugee camp of Bourj al-Barajneh during two such attacks between December 1985 and April 1987. All were treated in Haifa Hospital (30-40 beds), which had limited equipment, was situated inside the refugee camp and was badly damaged by war. During both attacks, the refugee camp was surrounded and put under siege such that patients could not be evacuated and supplies were not allowed in. The second period lasted almost 6 months resulting in severe shortages of medicines, equipment and food, leading to a rationing of resources and modification of treatment. More than 300 operations were carried out under general anaesthesia, the remainder under local or without anaesthesia. The overall operative mortality was 3.2 per cent. Despite the deprivation, many patients survived severe and complicated wounds because they were quickly brought to the hospital, provided with adequate quantities of fresh blood for transfusion, and sound surgical principles were followed. PMID- 1428170 TI - Magnetic resonance imaging of the knee: initial experience in a district general hospital. AB - We present the results of a prospective study comparing the accuracy of magnetic resonance imaging with arthroscopy in the assessment of knee complaints. Using a low field strength magnet, MRI was able to achieve a high diagnostic accuracy within the setting of a district general hospital. PMID- 1428171 TI - Gallbladder and extrahepatic biliary duct injury following abdominal trauma. AB - Extrahepatic biliary tract and gallbladder injuries are rare, but many occur after both blunt and penetrating abdominal trauma. During a 5-year period, 24 patients requiring laparotomy for abdominal trauma were found to have an extrahepatic biliary tract injury, representing 13 per cent of all patients admitted with hepatic trauma during the same period. The majority of patients had injury to the gallbladder; only one case of common bile duct injury was identified. Of the patients, 50 per cent had an associated hepatic injury; 17 per cent had important pancreatic trauma. Isolated gallbladder injury occurred in only 8 per cent of patients. The overall mortality associated with gallbladder trauma was 16 per cent. This uncommon injury usually results from severe trauma and is associated with a high incidence of other major visceral injuries. PMID- 1428172 TI - Bilateral Pipkin type I fractures. PMID- 1428173 TI - Bilateral Pipkin type II fracture of the femoral head. PMID- 1428175 TI - Monteggia equivalent injury in a very young patient. PMID- 1428174 TI - Fixation of fractures of the glenoid rim. PMID- 1428176 TI - Permanent tetraplegia in an infant following improper use of a car seat restraint. PMID- 1428177 TI - Laceration of the common hepatic duct bifurcation by blunt abdominal trauma. PMID- 1428178 TI - Acute upper airway obstruction due to a ruptured vertebral artery caused by minor cervical trauma. PMID- 1428179 TI - Bilateral ulnar neuropraxia: a complication of elbow crutches. PMID- 1428180 TI - Undisplaced fractures of the distal third of the radius in children: an innocent fracture? PMID- 1428181 TI - Importance of the environment and the faecal flora of infants, nursing staff and parents as sources of gram-negative bacteria colonizing newborns in three neonatal wards. AB - Gram-negative bacteria are an important cause of invasive infection among neonates. In this study a novel fingerprinting method was used for the first time to assess the importance of various potential reservoirs of the major gram negative enterobacteria that colonized 46 consecutive infants in three neonatal special care units during a three to four week period. Such bacteria were isolated from the oropharynx, umbilical cord and faeces in 24%, 33% and 100% of the infants, respectively. Klebsiella/Enterobacter spp. dominated over Escherichia coli and spreading (shared) over sporadic strains. Sixty-one percent of the neonates were colonized with at least one and up to six different strains shown to exist in the ward, mainly in other infants. Environmental reservoirs and the faecal flora of mothers and staff were of minor importance. Vertical transmission occurred in 12% of vaginally delivered infants and in 0% of those delivered by caesarean section. PMID- 1428182 TI - Antibiotic resistance of Escherichia coli in fecal samples of healthy people in two different areas in an industrialized country. AB - Fecal samples of 310 healthy persons, from two populations from different areas in the Netherlands, were examined for the presence of Escherichia coli resistant to ampicillin, tetracycline, sulfamethoxazole, trimethoprim and nitrofurantoin. High prevalences of resistance were found in both populations, ranging from 28% for trimethoprim to 89% for ampicillin. The percentages of the fecal samples with a dominantly resistant E. coli flora (> 50% resistance) were distinctly lower, ranging from 1% for nitrofurantoin to 21% for tetracycline. No significant differences in the level of resistance were observed between these two comparable populations in two different areas. The susceptibilities to 11 antimicrobial agents of 456 at random isolated E. coli were determined. The percentages of resistance varied widely: from 80% for chloramphenicol to 9% for nitrofurantoin. Only 19% of the isolates were susceptible to all antibiotics tested and 14% were resistant to more than four of the agents tested. Great differences in resistance rates between the two populations examined were seen for chloramphenicol (80% to 41%) and trimethoprim (16% to 36%). The results of this study underscore the presence of a human reservoir of antibiotic resistant microorganisms. PMID- 1428184 TI - Long-term persistence of anti-HBs after hepatitis B immunization in thalassaemic patients. AB - An epidemiological study was carried out on 114 beta-thalassaemics in order to select those subjects susceptible to hepatitis B virus (HBV) infection for hepatitis B vaccination. The results confirmed the high risk of HBV infection in these patients: 9.6% were HBsAg positive, 29.8% were anti-HBs positive/anti-HBc positive, and 9% were anti-HBc positive. In 60 HBV-negative patients, 20 micrograms doses of hepatitis B vaccine were administered on a schedule of 0, 1 and 6 months. Sera were collected for six years to determine the seroconversion rate and the anti-HBs titre. Seroconversion reached a maximum rate of 93% 12 months after the first vaccination dose and was 80% at the final control (72 months). Highly protective anti-HBs titres were observed until the last control in a high percentage of subjects. The HBVax hepatitis B vaccine has been shown to be safe, immunogenic and effective in beta-thalassaemics. PMID- 1428183 TI - Effectiveness of the macrolide clarithromycin in the treatment of Mycobacterium avium complex infection in HIV-infected patients. AB - In a randomized double-blind study, nine mycobacteremic patients with AIDS related disseminated Mycobacterium avium complex (MAC) infection received clarithromycin or placebo in addition to a basic regimen that included isoniazid, ethambutol and clofazimine. All four patients receiving clarithromycin showed blood culture conversion and clinical response. Of the five patients treated without clarithromycin, two showed resolution of mycobacteremia and clinical response, while another two died without having shown response. The remaining patient deteriorated until a switch from placebo to clarithromycin led to blood culture conversion and rapid clinical improvement. After finishing six weeks of intensive treatment, clarithromycin was given in an open maintenance phase to all patients, initially in combination with rifabutin for 24 weeks and then alone. One patient had a relapse of MAC infection while receiving clarithromycin alone. The relapse was associated with acquired resistance to the drug. Clarithromycin appears to be a promising component of multi-drug therapy for patients with MAC infection. Monotherapy can lead to drug resistance. PMID- 1428185 TI - Rapidly fatal Q-fever pneumonia in a patient with chronic granulomatous disease. AB - Acute Q-fever is a systemic illness which rarely has a fatal outcome. Fatal cases do occur with the chronic form of the disease and associated with endocarditis. This report presents the case of a fatal, acute Q-fever pneumonia in an 11-year old patient with chronic granulomatous disease. Complement fixation antibody titer rose to 1:1,024 with positive IgM in immunofluorescence. Giemsa stained lung sections and indirect immunofluorescence demonstrated the microorganisms in the tissues. The Coxiella burnetii infection was probably contracted during a holiday trip to rural France. Despite the fact that the patient received a variety of antimicrobial agents with broad spectrum activity against bacteria and fungi, coverage for Q-fever, i.e. chloramphenicol or tetracyclines, was not included. PMID- 1428186 TI - Listeriosis--a puzzling disease. PMID- 1428187 TI - Isolation of a multiresistant strain of Salmonella typhi in Italy. PMID- 1428188 TI - Mixed bronchial infection due to Mycobacterium tuberculosis and Mycobacterium avium-intracellulare in an AIDS patient. PMID- 1428190 TI - Silences: helping elderly Holocaust victims deal with the past. AB - Persons who have faced severe crises such as the Holocaust in Nazi Germany confront painful memories, guilt, and the perceived irrationality of their own survival, which represses thoughts and memories. There is no language to share the dark and difficult years of the past. Silence is their only voice of expression. In later life, when friends are gone, the need to share with others becomes urgent; to bear witness is vital. Helping persons share these experiences is no easy task. To engage the elderly with reminiscences, memory, bereavement, and the working through of guilt provide unusual challenges for the helping professions. Significant family events are also important opportunities for sharing the past. It is the children and grandchildren's desire to know that also prompts the sharing of past horrors and future hopes. They often enable the deepest silences to be shared and it is the elderly that often welcome this opportunity. Being sensitive to these integenerational dynamics are important in helping elderly Holocaust victims deal with their past. PMID- 1428189 TI - Loracarbef versus penicillin V in the treatment of streptococcal pharyngitis and tonsillitis. AB - Ten-day, double-blind, randomized, parallel treatment regimens of loracarbef (200 mg capsule twice daily or 15 mg/kg/day oral suspension in two divided doses up to a maximum of 375 mg/day; n = 169) and penicillin V (250 mg capsule four times daily or 20 mg/kg/day suspension in four divided doses up to a maximum of 500 mg/day; n = 175) were compared in the treatment of group A beta-haemolytic streptococcal (GABHS) pharyngitis and tonsillitis. Post-therapy clinical responses were similar for evaluable patients in both treatment groups: 97.4% of the loracarbef group (101/115 patients cured and 11/115 improved) and 96.0% of the penicillin group (101/124 patients cured and 18/124 improved). A statistically significant difference in the pathogen elimination rate was noted between treatment groups: post-therapy throat cultures were negative for GABHS in 94.8% (109/115) of loracarbef-treated patients compared with 87.1% (108/124) of penicillin-treated patients (p = 0.040). Loracarbef and penicillin V were comparable in terms of safety. Headache and nausea/vomiting were the most common events reported during therapy (nausea/vomiting were slightly less common in the loracarbef group). Three patients in each group were discontinued from the study due to drug-related adverse events; one due to rash in the loracarbef group and one due to rash and one due to vomiting in the penicillin group. These data support the conclusion that loracarbef twice daily is more effective in eradicating GABHS than penicillin V four times daily, and the two drugs are comparable in safety and clinical efficacy in the treatment of GABHS pharyngitis and tonsillitis. PMID- 1428191 TI - Widowhood in elderly women: exploring its relationship to community integration, hassles, stress, social support, and social support seeking. AB - This study examined the degree to which widows were integrated in their community, the daily hassles and stress they may have experienced, and their social networks and support-seeking behavior. A sample of 160 women, sixty years of age or older, eighty widows and eighty non-widows were interviewed. Half the sample participated in senior centers in Kansas City, Missouri, while the other half belonged to other organizations or were obtained through a truncated snowball technique. The findings indicated that widowhood in and of itself does not appear to be a predictor either of community integration or the lack of it or the experience of stress and hassles. Those who experienced hassles were not the same persons as those who experienced stress. It was surprising to find that those who sought social support did not seem most in need of it. Age and education, along with community integration, were better predictors of the variables studied than was widowhood. PMID- 1428192 TI - The influence of physical fitness on automatic and effortful memory changes in aging. AB - A cross-sectional study was carried out in order to determine the influence of cardiovascular fitness on age-related declines in cognitive performance. Forty eight volunteers were divided into Young (n = 13, 18-27 years), Middle-Aged (n = 22, 60-65 years) and Old (n = 13, 65-88 years) groups and tested on a battery of cardiovascular, pulmonary, hemodynamic, and biochemical tests in order to assess physical fitness. Cognitive performance was evaluated by a variety of memory tasks distributed along an automatic-to-effortful processing continuum. Memory for location and frequency of occurrence were selected as representative of automatic processing, whereas, an auditory free-recall task was selected as representative of effortful processing. Age-related performance declines were observed for the free-recall task, but no such age-dependent association was observed for frequency and location memory. With regard to the influence of physical fitness; the Middle-Aged and Older participants were divided into High and Low Fitness groups and significant differences were observed between these groups for the effortful but not the automatic memory tasks. These data suggest that the relationship between physical fitness and cognitive performance in old age is task dependent. Furthermore, the apparent prophylactic effects of physical fitness on effortful memory, do not appear to extend to cognitive tasks requiring less effortful processing. PMID- 1428193 TI - Predictors of self-reported problems of confusion among the aged. AB - Responses to questions on the 1984 Supplement on Aging to the National Health Interview Survey (NHIS) about the experience of personal confusion revealed that two-thirds of those interviewed reported never having an episode of confusion during the preceding year. Of those who reported episodes, fewer than one in five said they were happening with increased frequency. The many meanings of confusion found in the literature prompted a modest local study of what respondents understood by the term when asked the NHIS questions. Of those who admitted occasional confusion, almost two-thirds gave definitions that included memory loss or forgetfulness. Consequently, increased frequency of memory problems and difficulty in remembering were included with other variables in the analyses to identify significant predictors. They emerged the single best predictors of how often a respondent reported getting confused. Others were change in health status, number of functional limitations, educational attainment, and vision problems. PMID- 1428194 TI - Seniors' assessment of their health and life satisfaction: the case for contextual evaluation. AB - Health care professionals have been puzzled by the highly positive statements on health and life satisfaction made by seniors, particularly when compared to professionally collected data. In 1987-1988, a stratified, random sample of 520 seniors living independently in the community (70-99 years) were interviewed in their own homes. The above response pattern again held. However, it was apparent that opinions on life satisfaction vary with type of health problem. Content analysis of the spontaneous remarks made by the participants indicates that the overall, current, and anticipated levels of satisfaction expressed were associated significantly with the historical perspective or lifeview of the participants, and with their state of health. Utilizing the theoretical concept "sense of coherence" gives direction to understanding these phenomena. PMID- 1428195 TI - The human testis--an organ at risk? PMID- 1428196 TI - Pharmacokinetic and pharmacodynamic studies of the effect of ketoconazole on reproductive function in male rats. AB - A single oral dose (300 mg kg-1) of ketoconazole induced reversible immobilization of rat epididymal spermatozoa at 8-24 h after dosing. This occurred when the drug concentrations in cauda epididymal fluid and seminal plasma were at their peak (18.0 +/- 7.3 and 13.5 +/- 3.0 micrograms ml-1, respectively), and which was preceded by a peak plasma concentration (Cmax) of 64.82 +/- 2.47 micrograms ml-1 at 5.15 +/- 0.68 h (Tmax). In contrast, rete testis fluid collected from the same animals contained only minute amounts of ketoconazole (0.47 +/- 0.34 micrograms ml-1). Plasma testosterone concentration showed a sharp decline within 4 h of dosing, followed by a recovery from suppression, even after administration of a low dose (100 mg kg-1) which did not affect sperm motility. These findings suggest that ketoconazole gains access to the post-testicular sex organs and affects the mature spermatozoa therein much more readily than it affects testicular spermatogenesis. Synthesis and screening of compounds with a related molecular structure but which exhibit more pronounced spermicidal and less pronounced anti-androgenic effects are thus suggested in the hope that rapidly acting and reversible male contraceptives might be identified and developed. PMID- 1428197 TI - Testicular blood flow and vasomotion can be maintained by testosterone in Leydig cell-depleted rats. AB - The effect of testosterone supplementation on testicular blood flow, testicular vasomotion, the number of polymorphonuclear leucocytes (PMN's) in testicular blood vessels and prostatic blood flow were studied in rats in which the Leydig cell had been destroyed specifically by a single injection of ethane dimethylsulfonate (EDS). Other rats were supplemented with testosterone by subcutaneous injection of 25 mg testosterone propionate on days 1, 3 and 6. In some experiments, the effect of a single injection of 25 or 125 mg testosterone was studied. Testicular and prostatic blood flow and the number of PMN's in testicular blood vessels decreased, and vasomotion disappeared in Leydig cell depleted rats, but testosterone supplementation restored all parameters to normal values. Moreover, a single injection of testosterone was able to restore testicular and prostatic blood flow to normal levels but had an inconsistent effect on vasomotion. These results suggest that testosterone may play a role in the physiological control of the testicular microcirculation. PMID- 1428198 TI - Purification and characterization of phospholipase A2 from bovine prostate. AB - Phospholipase A2 (PLA2) was purified from bovine prostate by ammonium sulphate precipitation and fractionation by anion exchange chromatography, chromatofocusing and gel filtration. The purified enzyme was Ca(2+)-dependent and had a pH-optimum of 8.0. Ba2+, Fe2+, Hg2+, Mg2+, Pb2+, Sr2+ and Zn2+ as well as lysophosphatidylcholine, lysophosphatidylethanolamine and p-bromophenacyl bromide (p-BPB) inhibited the enzyme strongly. The enzyme had an estimated molecular weight of 12,000 +/- 1,000 daltons on SDS-PAGE. Isoelectric focusing showed one PLA2 activity-containing band at pl 5.3. The purified enzyme hydrolysed linoleic acid at the sn-2 position of phosphatidylcholine and phosphatidylethanolamine with high selectivity, compared to arachidonic acid. PMID- 1428199 TI - Relationship between sperm quality and chromatin condensation measured by sperm DNA fluorescence using flow cytometry. AB - DNA flow cytometry of sperm from 100 randomly chosen men undergoing fertility investigation revealed a general association between reduced sperm quality, as judged by conventional parameters, and the appearance of sperm with lower degrees of chromatin condensation in the ejaculate as measured by DNA fluorescence intensity. Chromatin hypocondensation, as measured by increased fluorescence, was manifested to different degrees in different samples. In many cases of more extreme sperm pathology, such as oligoasthenoteratozoospermia (OAT), the whole population of spermatozoa appeared to be affected. Significant numbers of hypercondensed spermatozoa were present in both normozoospermic men and men with different degrees of disturbance in sperm quality. All of the different parameters of sperm quality could be correlated significantly with certain of the flow parameters, although not one in particular could be used to predict deviations from the normal flow profile. In several asthenoteratozoospermic men and a small proportion of men with OAT, the DNA profiles were normal, implying that in these cases the disturbance may not be so fundamental. The presence of leucocytes in the ejaculate was associated with a general increase in the preponderance of hypocondensed subpopulations of spermatozoa in men with OAT as well as in normozoospermic subjects, emphasizing the effect of inflammatory conditions in the reproductive tract on sperm quality. PMID- 1428200 TI - Residual sperm function in oligozoospermia induced by testosterone enanthate administered as a potential steroid male contraceptive. AB - To investigate the fertility of men who remain oligozoospermic despite sex steroid suppression, the in-vitro fertilizing capacity of residual spermatozoa was assessed in 30 men receiving intramuscular testosterone enanthate (TE). Spermatozoa were prepared by either Percoll or repetitive centrifugation/washing. Although the mean (+/- SEM) pretreatment zona-free hamster oocyte penetration (HOP) rates were similar (59.4 +/- 10.1 and 63.8 +/- 10.8%), following the induction of oligozoospermia the Percoll-prepared spermatozoa exhibited a penetration rate (26.9 +/- 10.2%) which was markedly greater than that obtained for sperm prepared by repetitive washing (0 +/- 0%). In addition, the partners of two men exhibiting a HOP test with Percoll-prepared spermatozoa, conceived despite a sperm concentration of 3 x 10(6) ml-1 and a negative HOP test with spermatozoa prepared by repetitive washing. These results suggest that Percoll preparation optimizes the assessment of in-vitro sperm function and that the fertility of men with TE-induced severe oligozoospermia is suppressed but not abolished. PMID- 1428201 TI - Castration-resistant secretion in the hamster seminal vesicle does not depend on androgens. AB - The secretory activity of seminal vesicles (SV) in the castrated hamster was studied by stereological analysis and biochemical approaches following treatment with cyproterone acetate (CPA) and adrenalectomy in order to investigate whether extra-testicular androgens are responsible for castration-resistant protein secretion. Treatment of castrated animals with CPA decreased the size of secretory granules and increased the number of apical granules, though neither the absolute nor the relative volume of all the components analysed was changed. In addition, CPA-treatment increased the amount of protein exocytosed by SV in castrated animals, though total protein synthesis remained unchanged. Adrenalectomy neither suppressed secretion nor induced any further ultrastructural changes in the SV epithelium. Our results demonstrate that secretory activity of the hamster SV following castration is not controlled by extra-testicular androgens and suggest that SV secretory proteins, which are heterogeneous with regard to their sensitivity to androgen withdrawal, might be regulated differentially by androgens. PMID- 1428202 TI - Immunohistochemical localization of calmodulin in the human testis [corrected]. AB - The localization of calmodulin in the normal human testis was studied by the indirect immunoperoxidase method. Three different types of fixative were used: phosphate-buffered formalin, Bouin's solution or Carnoy's solution. Immunoreactivity specific for calmodulin was not detectable in the testis fixed in Carnoy's solution. The specimens fixed in phosphate-buffered formalin and in Bouin's solution were stained. The immunostaining for calmodulin was observed in pachytene spermatocytes, secondary spermatocytes and round spermatids but not in spermatogonia, or in pre-leptotene, leptotene and zygotene spermatocytes, elongated spermatids, spermatozoa or Leydig cells. Sertoli cells were not stained or were stained slightly. Among pachytene spermatocytes, the cells at the early stage were barely stained but those at the middle and late stages were slightly and intensely stained, respectively. The present report provides the first confirmation of the localization of calmodulin in the human testis. PMID- 1428203 TI - Is peritoneal dialysis the best choice for patients with severe heart disease? PMID- 1428204 TI - Mechanical issues in vascular grafting: a review. AB - Despite intensive research, the success of artificial small-diameter vascular grafts has yet to match that of natural grafts like the saphenous vein. One of the possible reasons is mechanical mismatch of the graft to the host vessel. The study of compliance (dilatability under pressure) has not been conclusive, especially after a series of recent investigations on vein graft evolution. Lately, the focus has been shifting towards more detailed characteristics, like anastomic behaviour, longitudinal elasticity, and flow-related variables. When the relevant property is identified, it should be included in the criteria for design and use of vascular prostheses. PMID- 1428205 TI - Effect of recombinant human erythropoietin (r-HuEPO) therapy on plasma FT3, FT4, TSH, FSH, LH, free testosterone and prolactin levels in hemodialysis patients. AB - The aim of this study was to evaluate the effect of r-HuEPO treatment on free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), free testosterone and prolactin levels in uremic hemodialysis patients. Twenty-four uremic hemodialysis patients were given r-HuEPO with a dose 60 U/kg as intravenous bolus injection at the end of each dialysis session. Once the hematocrit value of the patient had reached a range of 30-35%, the dose was adjusted so as to keep the hematocrit levels constant. Twenty uremic dialysis patients were taken as control group. The above-mentioned hormone levels of patients and control group were determined before and 4 months after r-HuEPO treatment. After the treatment, serum prolactin levels significantly decreased in both sexes (36.8 +/- 7.8 vs 22.9 +/- 6.3 ng/ml and 78.3 +/- 13.3 vs 37.4 +/- 10.4 ng/ml male and female, respectively). FT3 and FT4 significantly increased (1.17 vs 1.67 pg/ml, p < 0.05, and 0.64 vs 0.084 ng/dl, p < 0.05, respectively). TSH levels increased but those changes were not significant. There was no change in the level of any hormone in the control group. Also, the sexual functions of eight male patients treated with r-HuEPO improved and menstruation started again in four female patients. We concluded that r-HuEPO treatment especially decreases prolactin level in uremic hemodialysis patients. It is conceivable that correction of elevated prolactin levels could improve sexual disorders in these patients. PMID- 1428206 TI - Hemodialysis with defibrotide: effects on coagulation parameters. AB - In a crossover study conducted with eight uremic patients maintained on hemodialysis, the Authors compared the effects of heparin (100 IU/kg at the start of dialysis) and defibrotide (400 mg at the start, repeated at 2 hours of ongoing dialysis) on the parameters of blood coagulation (VIII:C, AT III, TAT, PC antigen and activity, PS, and FPA), each being assessed before dialysis and at 2, 3 and 4 hours of the ongoing procedure. Heparin-assisted dialysis resulted in a significant rise of VIII:C and AT III; with defibrotide, instead, there was evidence of thrombin activation (increased FPA and TAT). PC levels were raised with both dialysis modalities; however, PC activity and PS levels were increased only in defibrotide-assisted dialysis. There were no adverse reactions or evidence of fibrin formation. These results confirm the antithrombotic activity of defibrotide in the course of dialysis and indicate that this action is independent of thrombin neutralization. PMID- 1428207 TI - Nafamostat as anti-coagulant for membrane plasmapheresis in high bleeding risk patients. AB - Nafamostat mesilate (NM), an ultrashort-acting multi-enzymatic inhibitor, is a useful anti-coagulant in high bleeding risk patients needing hemodialysis. We applied NM as a membrane plasmapheresis (MP) anti-coagulant in patients with high bleeding risk. Eleven patients, the majority with hepatic failure and active hemorrhagic foci or severe bleeding diathesis, could be treated with MP 22 times under anti-coagulation by 20-40 mg/h/NM by continuous infusion without any trouble. Celite-activated coagulation time (CCT) at the plasma separator inlet and outlet was adequately prolonged during MP, but CCT in systemic blood showed no prolongation throughout the procedure, because NM was rapidly inactivated. There was no observable blood coagulation in the extracorporeal circuit including the plasma separator. No adverse reaction or exacerbation of hemorrhage was noted throughout the MP. NM thus appears to be a useful and safe anti-coagulant not only for hemodialysis but also for MP in high bleeding risk patients. PMID- 1428208 TI - Mayer waves in dogs with total artificial heart. AB - To assess the effect of a total artificial heart (TAH) on the autonomic nervous system a power spectral analysis of the hemodynamics in a TAH animal was done by the maximum entropy method. Two pneumatically driven sac-type ventricular assist devices were implanted as total biventricular bypass (BVB) in adult mongrel dogs to compare the differences between natural heart and TAH. Once the BVB was pumping, the natural heart was electrically fibrillated to constitute the BVB type TAH model. In the arterial pressure waveform in animals with TAH, respiratory waves were not changed (97.7 +/- 24.6%) though Mayer waves were significantly decreased (47.5 +/- 22.6%) compared with the animal with a natural heart. These results suggest that prosthetic hemodynamics in the TAH animal affect fluctuations in the cardiovascular system. PMID- 1428209 TI - Estimation of the following cardiac output using sympathetic tone and hemodynamics for the control of a total artificial heart. AB - A sympathetic neurogram is potentially useful for the development of a real time total artificial heart (TAH) control system. We used sympathetic tone and hemodynamic derivatives to estimate the following cardiac output in acute animal experiments using adult mongrel dogs. Moving averages of the mean left atrial pressure and mean aortic pressure were used as parameters of the preload and afterload, respectively. Renal sympathetic nerve activity (RSNA) was employed as a parameter of sympathetic tone. Equations for the following cardiac output were calculated using multiple linear regression analysis of the time series data. A significant correlation was observed between the estimated and following measured cardiac output. These results suggest the potential usefulness of the sympathetic neurogram for the real time TAH automatic control system. PMID- 1428210 TI - Results of randomized mitral valve replacement with mechanical prostheses after 15 years. AB - Between 1974 and 1976 150 consecutive patients (pts) were operated on for isolated mitral valve replacement (MVR). Bjork-Shiley (BS), Lillehei-Kaste (LK), and Starr-Edwards (SE) (type 6210) prostheses were implanted at random. All survivors were prospectively followed by regular clinical examinations every 6 to 12 months for 15 years. The mean follow-up time was 14.8 years. A constant subjective improvement after 15 years was reported in 62% of pts with BS, 30% with LK, and 49% with SE. The cumulative 14-year survival rate was 0.62 +/- 0.13 (BS), 0.56 +/- 0.16 (SE), and 0.54 +/- 0.15 (LK), respectively. Late mortality was due to thromboembolic events (n = 3), bleeding complications (n = 3), congestive heart failure (n = 7), documented arrhythmias or sudden death (n = 6). Thrombotic valve thrombosis (1 BS, 1 LK, 2 SE) required reoperations. Linearized cumulative rates after 14 years for thromboembolic complications were 14.2 +/- 3.1 (BS), 15.8 +/- 3.7 (SE), 24.3 +/- 4.2 (LK). The cumulative risk of severe bleeding complications was not different: BS: 35.8, LK: 35.2, SE: 34.3. During the first years of observation no significant differences between these mechanical prostheses could be observed, however, after 14 years of long-term follow-up the cumulative event-free rates were more favorable for the BS prosthesis. PMID- 1428211 TI - Hemocompatibility of titanium nitride. AB - The left ventricular assist device is based on the principle of the Maillard Wenkel rotative pump. The materials which make up the pump must present particular mechanical, tribological, thermal and chemical properties. Titanium nitride (TiN) because of its surface properties and graphite because of its bulk characteristics have been chosen. The present study evaluated the in vitro hemocompatibility of TiN coating deposited by the chemical vapor deposition process. Protein adsorption, platelet retention and hemolysis tests have been carried out. In spite of some disparities, the TiN behavior towards albumin and fibrinogen is interesting, compared with the one of a reference medical grade elastomer. The platelet retention test gives similar results as those achieved with the same elastomer. The hemolysis percentage is near to zero. TiN shows interesting characteristics, as far as mechanical and tribological problems are concerned, and presents very encouraging blood tolerability properties. PMID- 1428212 TI - Fast lysis by complement and uptake by liver of avidin-carrying biotinylated erythrocytes. AB - The fate of 51Cr-labelled avidin-carrying biotinylated erythrocytes after intravenous injection in the rat was examined. Surface amino groups of the erythrocyte membrane were modified by biotin N-hydroxysuccinimide ester. The biodistribution and stability of biotinylated erythrocytes in the blood were similar to those of non-biotinylated cells. Both types of cells circulated in the bloodstream for prolonged periods of time without substantial lysis (about 2-3% of injected radioactivity per g of blood for 24-48 hours, no more than 2% of lysis). Both types of erythrocytes were cleared by the spleen. The clearance of biotinylated cells was faster and more pronounced (peak of spleen uptake at 3 hours after injection, up to 35% of injected radioactivity per g of spleen), than that of nonbiotinylated cells (peak of spleen uptake at 24 hours after injection, up to 25% of injected radioactivity per g of spleen). Attachment of avidin to biotinylated cells results in extremely rapid lysis and clearance from the bloodstream (0.17% of injected radioactivity per g of blood 30 min after injection, 100% lysis). Radioactivity was rapidly cleared by the liver (up to 80% of injected dose per g of tissue, 70% per organ). Uptake by the spleen plays only a minor role in the clearance. Considerable lung uptake of avidin-carrying biotinylated erythrocytes was observed. Avidin-carrying biotinylated erythrocytes were lysed by fresh homologous serum in vitro in contrast to biotinylated and native cells. Lysis was eliminated by pretreatment of serum with EDTA or heating, which indicates a complement-dependent mechanism of lysis. PMID- 1428213 TI - Improved preparation of soluble dry oxyhemoglobin purified by carbontetrachloride treatment of outdated packed erythrocytes. AB - A combination of treating outdated packed red blood cells (PRBCs) with carbontetrachloride, countercurrent dialysis and modified conditions of freeze drying served to improve and standardize the technology of "stroma-free hemolysate" (SFH) in our laboratory. As a rule, proteins of the final product corresponded to 95% oxyhemoglobin, 3.5% methemoglobin and 1.5% non-hemoglobin ones. In freeze-dried samples stabilized with 0.24 molar saccharides, the weight proportions were 56% hemoglobin, 44% sucrose and/or 62% hemoglobin, and 38% fructose, respectively. If necessary, the saccharides could be rapidly removed from the easily reconstituted SFH by dialysis or chromatography. Analytical parameters were similar to those of chloroform-treated SFH stored dry at -12 degrees C for 4 months. However, the present procedure was easier and SFH samples remained unchanged after dry storage even at +4 degrees C for at least 13 months. This oxyhemoglobin product seems suitable for organ perfusion, further chemical modification and as an analytical standard. PMID- 1428214 TI - Application of an essential data set based computer system in support of maternal and child care. AB - A simple functional application software has been developed to support care providers in information management related to perinatal care activities, family planning encounters and the immunization of infants. This was distributed to some sites and was implemented with no organizational change, though the methods differed. An early assessment of the software after a period of implementation is made based on the observations and experiences reported. This is presented in a framework outlined earlier as the OUST model. The systems objective to enhance the value of information was observed to have been partially achieved. The utility to the users is observed in the ability of the end-users at the sites to identify the local community needs and adopt accordingly suitable strategies. The social impact was seen in the assistance provided by the sentinel action of the system in tracking dropouts from the immunization programme at a site, thereby ensuring quality in care and also economic benefits. From a technical standpoint, the application software was small yet functional and in it were incorporated features that ensured data quality. The application software was designed to generate a unique identity code to assist in follow-up of the target population. Based on the data entered it compiled reports to meet administrative requirements, reports that gave the care providers feedback and lists to coordinate in the follow-up of the target population. The application software is a common data collection tool that can assist in building a data registry for health outcomes research. PMID- 1428215 TI - Multidimensional scaling of head and neck metastases. AB - A mathematical analysis, called multidimensional scaling, was applied to two sets of data on metastases from head and neck cancers. The analysis places lymph nodes in an imaginary space (here termed a 'nodalgram') such that distances between nodal clusters are proportional to differences in the occurrence of tumor metastases. Two-dimensional scaling explains 93% of the variance in clinical data from 1008 patients and 91% of the variance in pathological data from a different set of 415 patients. These independent results are closely correlated, and both explain vastly more of the data than expected by chance. The dimensions of the nodalgram are not related to anatomical coordinates of the nodes, suggesting that a representation of these structures in an abstract space explains the spread of cancers better than an analysis of spread in real space. Surprisingly, a plot of the extent to which metastases from different primary sites spread along the nodalgram dimensions is closely related to the normal anatomical locations of the primaries. This shows that although the nodalgram may be difficult to interpret, it must have some biological significance. In conclusion, multidimensional scaling successfully quantifies a pattern in the spread of head and neck cancers. PMID- 1428216 TI - Bodymap: an image processing system for the measurement of body surface profiles encountered in skin expansion surgery. AB - A personal computer based image processing system for the mapping and subsequent analysis of local areas of the human body requiring no more than 180 degrees of vision is described. The operations of image capture and data extraction are undertaken in real time and photogrammetric reconstruction takes typically a further 30 s. Accuracy of the system has been assessed by photogrammetrically reconstructing 37 points whose coordinates had been precisely established by traditional survey techniques. An average discrepancy between surveyed and reconstructed positions of 0.485 mm was obtained; this level of accuracy compares highly favourably with results achieved using alternative methods and which do not have the level of automation inherent in the described system. The system has been developed specifically to provide quantitative values for parameters of particular interest in skin expansion surgery: consequently the post reconstruction facilities available in this initial system are surface area and enclosed volume calculations and shaded surface display. Further development work currently in progress is also briefly discussed. PMID- 1428217 TI - Time trends of smoking cessation: a micro-population computer simulation model. AB - The Micro-population model of Risk-group Dynamics (MRD) approaches smoking behavior at the level of the individual and integrates physiological and social factors to describe the evolution of behavior change in the population. MRD is innovative in several ways: (1) the model describes mathematically the interactions among these behavioral factors; (2) the model accounts for both the variability of these factors among different persons and the universality of basic rules describing these factors in all individuals; and (3) the model can be applied to various types of populations and a wide range of intervention strategies. MRD combines the physiological, psychological and social determinants into a hazard function for relapse to smoking. This hazard function is then organized into a three term expression incorporating: a baseline hazard characteristic to each individual, a decreasing term for the diminishing aspect of the initial hazard and an effect of external interventions. The model gives promising results when applied to the Multiple Risk Factors Intervention Trial (MRFIT) data using the assumptions of a Weibull distribution for the baseline hazard, a negative exponential for the decrease in the initial hazard and a constant intensity for the external intervention. PMID- 1428218 TI - An application of computer conferencing in dental education. AB - A computer conference was used as an instructional tool in a dental school course on health education. Second year students (N = 84) were divided into 17 groups to design community education programs. A student from each group participated in the conference to electronically discuss their program with peers. The conference operated for 52 days. The 28 conference topics were displayed 1028 times. There were 279 conferencing uses lasting 8125 min (135.4 h); a mean of 29.1 min/use. Mean responses per students was 25. Mean student terminal time was 7.8 h. Instructor terminal time was 20.8 h; 5.4 h were spent managing the conference. Of the available conferencing funds ($440.00), $218.35 was expended with students using $168.24. Mean dollars spent per student was $9.90. Quantitative evaluation of participation was based on: (a) number of individual responses made compared to mean responses; (b) timely item placement on the conference; and (c) the percentage of responses made in other students' items. Student evaluation of conferencing was positive and acknowledged the value of computer skills. PMID- 1428219 TI - Simulation of a diffusion process with randomly distributed jumps in neuronal context. AB - In stochastic neuronal models, an interspike interval corresponds to the time interval during which the process imitating the membrane potential reaches a threshold from an initial depolarization. For neurons with an extensive dendritic structure, a stochastic process combining diffusion and discontinuous development of its trajectory is considered a good description of the membrane potential. Due to a lack of analytical solutions of the threshold passage distribution for such a process, a method for computer simulation is introduced here. For the diffusion Ornstein-Uhlenbeck process with exponentially distributed moments of constant jumps a program is given. The relation between the simulation step, accuracy of simulation and amount of computing time required is discussed. PMID- 1428220 TI - Application of autoregressive analysis to 20 MHz pulsed Doppler data in real time. AB - The real time application of autoregressive (AR) spectral analysis to a 20-MHz pulsed Doppler blood flowmeter is presented. The system consists of a TMS 320C25 digital signal processor with a 80286 based PC/AT microcomputer and associated interfacing circuitry. The AR method was used for in vivo spectral analysis of the signals obtained from a 20-MHz pulsed Doppler flowmeter in real time. The data obtained from digital and coronary arteries were processed using both AR and FFT spectral analysis methods. Also the data obtained from a stenosis coronary artery under surgical operation were processed using both methods. When the results are compared, it is seen that autoregressive analysis has given better results. Therefore the technique can be used in the examining of small vessels such as renal, iliac, mesenteric, coronary and digital arteries. PMID- 1428221 TI - Seasonal variation and meteotropism in various self-rated psychological and physiological features of a normal couple. AB - Recently, true seasonal variation with significant periodicities (circannual, semiannual, circatrimensual, circabimensual) and a significant meteotropism have been observed in a number of self-rated characteristics of normal man (arousal, mood, physiology and social behaviour). In order to replicate these findings, two normal controls (a married couple) were asked daily to complete a self-rating scale concerned with the characteristics mentioned above during one calendar year. By means of time series analysis, significant rhythmicities with recurrent cycles in the autorhythmometric data of all of the above characteristics were found. An important part of the variance in these characteristics was found, using multiple regression, to be related to various weather variables, such as mean atmospheric pressure, temperature, relative humidity, wind speed, minutes of sunlight/day and precipitation/day. These results support the hypothesis that temporal variations in human psychological and physiological characteristics may be dictated by the composite effects of past and present atmospheric activity. PMID- 1428222 TI - Mast cells in the human lung at high altitude. AB - Mast cell densities in the lung were measured in five native highlanders of La Paz (3600 m) and in one lowlander dying from high-altitude pulmonary oedema (HAPO) at 3440 m. Two of the highlanders were Mestizos with normal pulmonary arteries and the others were Aymara Indians with muscular remodelling of their pulmonary vasculature. The aim of the investigation was to determine if accumulation of mast cells in the lung at high altitude (HA) is related to alveolar hypoxia alone, to a combination of hypoxia and muscularization of the pulmonary arterial tree, or to oedema of the lung. The lungs of four lowlanders were used as normoxic controls. The results showed that the mast cell density of the two Mestizos was in the normal range of lowlanders (0.6-8.8 cells/mm2). In the Aymara Indians the mast cell counts were raised (25.6-26.0 cells/mm2). In the lowlander dying from HAPO the mast cell count was greatly raised to 70.1 cells/mm2 lung tissue. The results show that in native highlanders an accumulation of mast cells in the lung is not related to hypoxia alone but to a combination of hypoxia and muscular remodelling of the pulmonary arteries. However, the most potent cause of increased mast cell density in the lung at high altitude appears to be high-altitude pulmonary oedema. PMID- 1428223 TI - Effect of air temperature and humidity on ingestive behaviour of sheep. AB - Thirty-two Polwarth ewes, of ages up to 1 year, were observed in a climatic chamber (24 to 45 degrees C) for eight periods of 5 h each. The observations were made through a window in the chamber wall. All animals were observed four times, then shorn and observed four times again. The animals were given weighed quantities of water and feed consisting of commercial concentrate plus Rhodes grass (Chloris gayana) hay. The water and feed remaining after 5 h of observation were weighed. The following traits were analysed: time eating hay (TEH), time eating concentrate (TEC), time drinking water (TDW), weight of hay eaten (WHE), weight of concentrate eaten (WCE), volume of ingested water (VIW), ruminating time standing up (RTS), ruminating time lying down (RTL), idling time standing up (ITS), and idling time lying down (ITL). Shearing had a significant effect for all traits except ITS. Shearing resulted in higher values for all traits except for ITS and ITL. Ingestion of hay (TEH and WHE) decreased with increased air temperature and humidity, while the ingestion of concentrate (TEC) and WHE) and water (TDW and VIW) increased. Rumination decreased with increased air temperature and humidity, and was higher in shorn than in unshorn sheep. PMID- 1428224 TI - Influence of hot environments on some blood variables of sheep. AB - Thirty-two Polwarth sheep of ages up to 1 year were observed under temperatures varying from 10.5 to 46.5 degrees C. The following blood cell counts were made: erythrocyte (RBC), leucocyte (WBC), eosinophil (EOS), neutrophil (NEU), lymphocyte (LYM) and monocyte (MON). Other traits measured were: haemoglobin (HB), haematocrit (HT), blood glucose (GLU) and serum protein (PROT). Multivariate analysis of variance was used and the results showed a significant (P < 0.001) effect for the interaction of shearing and temperature treatment. Under temperatures > 25 degrees C, sheep presented a decrease of RBC, WBC, HB and HT, these differences being greater in the shorn than in the unshorn animals. Unshorn animals presented higher variations in EOS, NEU, LYM, MON and GLU. Blood glucose increased under high temperatures in the shorn animals (from 56.36 +/- 0.65 mg/100 ml to 60.52 +/- 0.69 mg/100 ml) as in the unshorn animals (from 54.72 +/- 0.74 mg/100 ml to 57.56 +/- 0.77 mg/100 ml). PMID- 1428225 TI - Geomagnetic activity and enhanced mortality in rats with acute (epileptic) limbic lability. AB - Presumably unrelated behaviors (e.g. psychiatric admissions, seizures, heart failures) have been correlated with increased global geomagnetic activity. We have suggested that all of these behaviors share a common source of variance. They are evoked by transient, dopamine-mediated paroxysmal electrical patterns that are generated within the amygdala and the hippocampus of the temporal lobes. Both the probability and the propagation of these discharges to distal brain regions are facilitated when nocturnal melatonin levels are suppressed by increased geomagnetic activity. In support of this hypothesis, the present study demonstrated a significant correlation of Pearson r = 0.60 between mortality during the critical 4-day period that followed induction of limbic seizures in rats and the ambient geomagnetic activity during the 3 to 4 days that preceded death; the risk increased when the 24 h geomagnetic indices exceeded 20 nT for more than 1 to 2 days. PMID- 1428226 TI - Lung cancer following Hodgkin's disease: a case-control study. AB - It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer. A collaborative group of population-based cancer registries and major treatment centers carried out a case-control study, in which 98 cases of lung cancer were identified in patients who had survived at least 1 year following a diagnosis of Hodgkin's disease. A total of 259 matched controls were selected from patients with Hodgkin's disease who did not develop subsequent lung cancer, and for both cases and controls detailed information was abstracted from medical records concerning stage and treatment of Hodgkin's disease. Patients treated with chemotherapy alone had about twice the risk of developing lung cancer than those treated by radiotherapy alone or both modalities. There was no increase in risk with cumulative number of cycles of chemotherapy. Among patients treated with radiotherapy alone, there was an increase in risk related to estimated radiation dose to the lung. There was also a strong association between cigarette smoking and the risk of lung cancer. The finding of a higher risk following chemotherapy than following radiotherapy was unexpected, but could not be explained by any identified methodological flaws. A plausible inference from the study is that all forms of Hodgkin's disease therapy are carcinogenic to the lung and that, in particular, chemotherapy is associated with an increase in risk which is at least comparable to and perhaps higher than the risk produced by radiotherapy. PMID- 1428228 TI - Differences in expression of SPan-1 and CA15-3 antigens in blood and tissues. AB - Pancreatic and mammary cancer cells are reported to have different oligosaccharides on the same apomucin, the MUCI gene product. A better understanding of the tissue specificity of these sugar structures may help in identifying the source of mucins when they are found in the sera. Serum levels of 3 pancreatic-cancer-associated carbohydrate epitopes identified by monoclonal antibodies (MAbs) SPan-1, 19-9 and DU-PAN-2, were compared to those of CA15-3 in a variety of malignant conditions. CA15-3 identifies both carbohydrate and peptide determinants associated with the MUC1 apomucin in breast tissues. SPan-1 antigen was elevated in a high percentage of patients with pancreatic, gastric and colorectal cancer but in only a few of the patients with malignancies of non GI origin such as breast, ovary and lung. The 19-9 and DU-PAN-2 antigens had a similar pattern of much greater sensitivity for pancreatic cancer than for these non-gastrointestinal cancers. The levels of these 3 markers showed significant correlations in pancreatic cancer. In contrast, CA15-3 was elevated in a large number of patients with breast, lung, ovarian and pancreatic cancers. There was no correlation of CA15-3 with the 3 other markers in pancreatic cancer. SPan-1 and DF3/115D8 antigens in blood have different mobilities in SDS-PAGE and buoyant densities. Moreover, SPan-1 and DF3 antigenic determinants are localized in different regions of the same normal and malignant pancreas and breast tissues. Thus the SPan-1 determinant can be dissociated from the breast peptide and/or carbohydrate determinants. PMID- 1428229 TI - Effect of DNA ploidy classification on prognosis in breast cancer. AB - A series of 327 breast cancers was analyzed for DNA ploidy by flow cytometry from paraffin-embedded tissue, and the resulting DNA histograms were classified independently by 6 researchers in the field as DNA diploid (Di), aneuploid (An), tetraploid (Te), multiploid (Mu), or technically uninterpretable. The frequency of diploid, aneuploid, tetraploid and multiploid cancers varied from 28 to 41%, 33 to 49%, 8 to 21% and 2 to 6%. According to the scale Di-An-Te-Mu, DNA ploidy was not significantly associated with breast-cancer mortality by 2 classifiers, but if DNA euploid cancers (Di+Te) were tested against non-euploid, or diploid cancers against non-diploid, all classifiers found DNA euploid and diploid cancers to have better prognosis. Mortality associated with diploid or tetraploid cancers decreased with improving histogram quality and increasing uniformity of classification, whereas that associated with aneuploid cancers remained unaltered. Among the cases where all classifiers agreed on ploidy, tetraploid, diploid and aneuploid cancers were associated with 100%, 88% and 68% 5-year survival rates. In this sub-set the S-phase fraction and possibly DNA ploidy were independent prognostic factors, together with histological grade, axillary node status, and primary tumor size. PMID- 1428227 TI - Variations in the ganglioside profile of uveal melanoma correlate with cytologic heterogeneity. AB - Gangliosides may play an important role in the proliferation and spread of human malignant melanoma. Because the frequency of metastases in uveal and cutaneous melanoma differs, it is possible that they may express different gangliosides. We analyzed the ganglioside profiles of primary uveal melanoma in 14 cases and of cutaneous melanoma metastasis in 19 cases. In cutaneous melanoma, GM3 ranged from 4.2% to 74.6% and GD3 from 22.1% to 91.8% of total lipid-bound sialic acid. GM2 (found in 13 of 19 cases, ranging from 0.5% to 11.7%), GD2 (11/19, 0.5%-22.0%) and 9-O-acetyl-GD3 (13/19, 0.5%-12.6%) were also frequently observed. By contrast, in 11 cases of uveal melanoma, GM3 was > 90%, GD3 was < 10%, GM2 was < 1.1%; neither GD2 nor 9-O-acetyl-GD3 were detected. The ganglioside profiles of these uveal melanomas were virtually identical to those of normal melanocytes obtained from foreskins. Histological examination of these 11 biopsies showed a monomorphous cell composition, but neither infiltration of lymphocytes or melanophages nor cell necrosis was observed. In 3 other cases, GD3 was increased to 19.5%-46.0%. Histological examination of these 3 biopsy specimens showed at least 2 populations of tumor cells that were separable based on morphological grounds, and mononuclear inflammatory cells interspersed among the tumor cells. An increase in GD3 appears to be related to tumor polyclonality and infiltration of the tumor by lymphocytes and macrophages. These results suggest that ganglioside expression of uveal melanoma is associated with host immune responses to the tumor. Furthermore, the low metastatic capacity of uveal melanoma, in contrast to the high metastatic rate of cutaneous melanoma, may be a result of its differentiated ganglioside expression, which is strikingly similar to that of normal melanocytes. PMID- 1428230 TI - Breast cancer and timing of surgery during menstrual cycle. A 5-year analysis of 385 pre-menopausal women. AB - It has been proposed that the timing of breast-cancer surgery in relation to menstrual phase has a prognostic impact on outcome. We carefully evaluated a combined 2-center series of 385 pre-menopausal women operated on for stage-I and stage-II breast cancer with a median follow-up of 5 years for a possible impact on outcome of the date of their last menstrual period (LMP) before surgery. The distribution of risk factors of the study cohort as well as prognostic indicators corresponded to previously published results. Nodal status, grading, and (in part) hormone-receptor status differentiate well between patient subgroups with high and low risk of relapse and death after breast-cancer surgery. In neither univariate nor multivariate analysis was any impact of the so-called "unopposed" estrogen secretion detected. We did not observe any effect of LMP on long-term survival in any of several prognostic subgroups, in particular in hormone receptor-positive patients. From our results and from the literature, we conclude that LMP does not provide any prognostic information for outcome after breast cancer surgery and therefore the proposed modification of scheduling of breast cancer operations is not justified. PMID- 1428231 TI - H-2Db gene transfer into highly metastatic D122 cells results in tumor rejection in allogeneic recipients, but does not affect metastasis in syngeneic recipients. Implications for mechanisms of allorejection. AB - Highly metastatic, weakly immunogenic Lewis lung carcinoma clones express very low levels of H-2Kb and moderate levels of H-2Db class-I major histocompatibility complex antigens. These cells metastasize spontaneously in mice with C57BL/6 genetic background possessing the H-2Db locus, and grow as local tumors across allogeneic barriers. Transfection of the H-2Db genes into the highly metastatic clone D122 did not alter the growth or metastatic capacity of these cells in syngeneic mice. However, these cells were rejected in allogeneic mice. Transfection of the H-2Kd or H-2Kk genes into D122 elicited a CTL population that cross-reacted with cells bearing native H-2Db antigens. These data suggest that overlapping allo-CTL populations are induced by a native alloantigen and by alloantigen peptides presented through self class-I molecules. PMID- 1428232 TI - Regulation of androgen receptor gene expression by steroids and retinoic acid in human breast-cancer cells. AB - Although the androgen receptor (AR) has been detected by ligand-binding assays, there is little known about the expression and regulation of the AR gene in human breast-cancer cells. AR mRNA, measured by Northern analysis in 18 cell lines, was found to be expressed predominantly in oestrogen- and progesterone-receptor positive (ER+, PR+) lines as a single species of approximately 10.5 kb but was also comparatively abundant in I ER- and PR-negative cell line, MDA-MB-453. Dexamethasone (Dex), Organon 2058 (Org 2058), dihydrotestosterone (DHT), and all trans-retinoic acid (RA) down-regulated AR mRNA levels in T-47D (ER+, PR+) cells 6 hr after treatment, whereas oestradiol (E2) had no effect. In MDA-MB-453 (ER-, PR-) cells, regulation of AR mRNA by RA differed from the other cell lines: RA increased the level of AR mRNA. DHT-binding assays indicated a corresponding increase in AR protein. Transfection of the androgen-responsive mouse mammary tumour virus long-terminal repeat (MMTV LTR) linked to a chloramphenicol acetyltransferase (CAT) reporter gene was used to examine the effect of altered AR levels on androgen action. The increased level of AR following RA pre treatment in MDA-MB-453 cells resulted in enhanced induction of CAT activity by DHT and, conversely, a decrease in the level of AR following RA pretreatment in T 47D cells resulted in reduced induction of CAT activity by DHT. These data demonstrate that AR is expressed predominantly in ER+ and PR+ cell lines and its expression is regulated by ligands also known to regulate ER or PR, including progestins and retinoids. Androgen responsiveness measured by a transfected reporter gene was altered according to the extent of up- or down-regulation of AR expression, demonstrating that responsiveness is dependent on receptor concentration. PMID- 1428233 TI - Specific cytogenetic abnormalities and k-ras mutation in two new human colorectal adenoma-derived cell lines. AB - Two new human epithelial cell lines from sporadic colorectal adenomas designated S/RR and S/BR are reported. Both cell lines have extended growth capacities in vitro, reaching passages 38 and 40 respectively and show no sign of senescence. S/RR and S/BR cell lines have retained the ability to differentiate in vitro, as shown by mucin production from goblet-like cells. S/BR was derived from a large colonic tubular villous adenoma (3 to 4 cm), whereas S/RR was derived from a small rectal adenoma (< 1 cm), and may represent a relatively early-stage adenoma. The parent S/RR cell line has given rise to a clonogenic variant, designated S/RR/Cl, which also has shown no sign of senescence and has currently reached passage 43. Both the S/BR and the S/RR cell lines had mutations in codon 12 of the K-ras gene, while retaining one normal allele. The presence of this mutation, particularly in the cell line S/RR derived from a small adenoma, is consistent with ras mutation being a relatively early event in colorectal carcinogenesis and is perhaps involved in the ability of the adenoma cells to progress and to give rise to an immortal cell line in vitro. The clonal derivatives of the S/RR cells have an isochromosome 1q and abnormalities of chromosome 13 which include an isochromosome 13q. The S/BR cells have a deletion on the short arm of chromosome 1 and trisomy 7. The common abnormality for S/RR and S/BR cells involves chromosome 1. The involvement of different chromosomes in the 2 cell lines also suggests different pathways for malignant progression of the premalignant adenoma cells. PMID- 1428234 TI - Effect of IL-1 on experimental bone/bone-marrow metastases. AB - Bone metastasis is a common event and a major cause of morbidity in cancer patients. The hematopoietic marrow of the bones, rather than the bone tissue per se, is the target organ in bone metastasis. In the bone marrow, IL-1 induces the release of hematopoietic growth factors that may affect tumor-cell growth. We treated groups of mice with rhuIL-1 alpha to examine its role in the establishment of experimental bone/bone-marrow metastasis. We found that injection of 2 micrograms of rhuIL-1 alpha 24 hr prior to, simultaneously with or 24 hr after the injection of 10(4) B16 melanoma cells into the left cardiac ventricle of mice resulted in a 2-fold increase in the average number of colonized bones per mouse. GM-CSF is produced by bone-marrow stromal cells in response to IL-1, and its receptor has been found on tumor cells, including melanoma cells. However, the administration of rmuGM-CSF to mice by either multiple injections or continuous infusion did not affect the number of colonized bones. Many of the biologic effects of IL-1 are mediated by prostaglandins. Treatment of mice with 100 micrograms of indomethacin, a potent inhibitor of prostaglandin synthesis, prior to the injection of rhuIL-1 alpha, prevented the increase in number of bone metastases. To determine whether constitutive productions of IL-1 and/or prostaglandins are involved in the pathogenesis of bone/bone marrow metastasis, we treated mice with antimouse IL-1 alpha neutralizing antibodies, rhuIRAP (an inhibitor of IL-1 activity) or indomethacin. We found no difference in the average number of colonized bones per mouse between treated and control mice. We conclude that exogenous administration of IL-1 enhances experimental bone/bone-marrow metastases, and that this phenomenon is mediated through prostaglandins. However, neither the constitutive production of IL-1 nor that of prostaglandins appear to play a role in the pathogenesis of bone/bone-marrow metastasis in our murine model system. PMID- 1428235 TI - Inhibition by 6-hydroxydopamine of enhanced gastric carcinogenesis induced by N methyl-N'-nitro-N-nitrosoguanidine in spontaneously hypertensive rats. AB - The effects of chemical sympathectomy induced by 6-hydroxydopamine (6-OHDA) on the enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N nitrosoguanidine (MNNG) in spontaneously hypertensive rats (SHR), and the norepinephrine (NE) concentrations in their gastric wall and the labeling index of gastric epithelial cells were investigated. SHR rats and normotensive Wistar Kyoto rats (WKY) as controls were given MNNG (25 micrograms/ml) in their drinking water for 25 weeks and then i.p. injections of 6-OHDA (42 mg/kg twice within 24 hr, and then 105 mg/kg every 2 weeks from 1 week later). In control group (WKY rat + NaCl), gastric cancers were found in 2 (11%) of 18 rats examined in week 52. In SHR rats treated with NaCl solution only, the incidence of gastric cancers significantly increased, to 53% compared with that in control WKY rats. Treatment of SHR rats with 6-OHDA significantly decreased its incidence to 12% compared with the value in SHR rats treated with NaCl solution only. Prolonged administration of 6-OHDA to SHR rats significantly reduced the NE concentration in the antral portion of the gastric wall and the labeling index of antral epithelial cells. These findings indicate that prolonged i.p. treatment with 6 OHDA attenuated the normally higher incidence of MNNG-induced gastric cancer in SHR rats. PMID- 1428236 TI - Enhancement of cisplatin activity by lonidamine in human ovarian cancer cells. AB - The ability of lonidamine, an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxicity of cisplatin was investigated in human ovarian cancer cell lines sensitive (A2780) or with experimentally induced resistance (A2780/cp8) to the alkylating agent. A 24-hr post-incubation with 300 microM lonidamine significantly potentiated the activity of a 1-hr cisplatin treatment in both cell lines. In particular, the cisplatin IC50 value was reduced 4-fold in the sensitive line and 5-fold in the resistant line. Flow cytometric analysis showed that, in the resistant cell line, lonidamine alone did not affect cell kinetics, but when given after cisplatin it was able to transform the temporary G2 + M cell accumulation induced by the alkylating agent to a persistent block in S/G2 + M. In the A2780/cp8 cell line, lonidamine was also able to significantly enhance the accumulation of cisplatin-induced DNA interstrand cross-links. Our results suggest that lonidamine can positively modulate the anti-tumor activity of cisplatin in ovarian cancer cells and also indicate that the drug is potentially useful in combination therapy including the alkylating agent for ovarian cancer patients. PMID- 1428237 TI - Human gene MAGE-1, which codes for a tumor-rejection antigen, is expressed by some breast tumors. PMID- 1428238 TI - Percutaneous transluminal coronary angioplasty in patients aged 70 years and older: immediate and long-term results. AB - We analyzed all coronary angioplasty procedures performed in patients aged greater than 70 yr since 1987. There were a total of 92 patients with a mean age of 74 +/- 4 yr (range 70-82). The clinical diagnosis was unstable angina in 79%. Single-vessel disease was present in 41%, double-vessel in 29% and triple-vessel in 30% of patients. A left ventricular ejection fraction of less than 40% was present in 18 patients. Angioplasty was attempted on one vessel in 52 patients (56%), on two vessels in 29 patients (32%) and in three vessels in 10 patients (11%). Angiographic success was achieved in 96% of stenoses and in 53% of chronic total occlusions attempted. Complete revascularization was achieved in 56% of patients. Complications included three patients (3.2%) who underwent emergency coronary artery bypass grafting, 1 patient (1.1%) who sustained a myocardial infarction and 5 patients (5.4%) who died. During hospitalization, which averaged 3 +/- 2 days, 1 patients sustained reversible renal failure and 5 patients required blood transfusion for a large groin hematoma. Clinical success at discharge was 83%. At a mean follow-up of 13 months (range 3-45 months), symptomatic improvement was observed in 59 of the 76 patients who had achieved clinical success, with 42 of these patients (55%) being asymptomatic. The following clinical events occurred: myocardial infarction in 1 patient, new percutaneous transluminal coronary angioplasty in 9 and 3 patients died of cardiac reasons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428239 TI - Metabolic adaptation of myocardial mitochondria to mild altitude hypoxia. AB - We studied the metabolic parameters of myocardial mitochondria (respiration, respiratory control index, oxidative phosphorylation rapidity and coefficient of oxidative phosphorylation) in two groups of rats: one living at an altitude of 140 m above sea level (control group) and the other living from birth at an altitude of 1350 m above sea level for 2 and 4 months (experimental group). Compared with the control rats, the experimental rats during 2 and 4 months of mild altitude acclimatization increased their basal and stimulated respiration, as well as the rapidity of energy production by myocardial mitochondria. The coefficient of oxidative phosphorylation under mild altitude hypoxia decreased but the respiratory control index did not change. We explain these alterations of heart muscle metabolism at the mitochondrial level as an adaptation to the mild hypoxic conditions. PMID- 1428240 TI - Cardiac tamponade as presentation of systemic amyloidosis. AB - We present a patient with pericardial tamponade due to amyloid heart disease. A 64-yr-old man was admitted to the hospital because of fatigue and the abrupt development of chest pain and dyspnea. Echocardiography showed severe pericardial effusion and total pericardiectomy was necessary. Ten months later laboratory studies revealed proteinuria and high serum creatinine. A rectal biopsy showed amyloid deposition that was also found in the pericardial tissue. Pericardial tamponade is an extremely rare complication of cardiac amyloidosis. To our knowledge, only one previous case of cardiac tamponade due to amyloid heart disease has been reported. PMID- 1428241 TI - "Serpentine heart". Direct observation of the human heart during profound hyperkalemia. AB - We observed cardiac contractility in a patient who had inadvertently received a massive overdose of potassium chloride during open heart surgery. Slowly advancing waves of contraction were present while the surface electrocardiogram showed the sine wave configuration typical of severe hyperkalemia. This is the first report of such an observation and may serve to promote proper diagnosis and treatment of similar cases. PMID- 1428242 TI - Coronary-cameral fistula in association with Klinefelter syndrome: exercise induced ventricular tachycardia late after surgical ligation. AB - Twenty two years after surgical ligation of a large coronary-cameral fistula originating from the circumflex artery and terminating to the right atrium, non sustained exercise-induced ventricular tachycardia occurred in a 26-year-old male with known Klinefelter (XXY) syndrome. Cardiac catheterization showed satisfactory closure of the defect, but also revealed occlusion of the circumflex coronary artery, associated with inferolateral infarction. PMID- 1428243 TI - Absence of the right superior caval vein associated with disease of the sinus node. AB - Absence of the right superior caval vein has been shown by postmortem studies of infants and children to be associated with histological abnormalities of the sinus node. We report the case of a 32-yr-old man who presented with syncope due to disease of the sinus node and was found to have absence of the right superior caval vein. He was successfully managed with implantation of an epicardial atrioventricular sequential pacemaker. PMID- 1428244 TI - Common arterial trunk with absence of the left pulmonary artery in a 32-year-old man. AB - We report a case of common arterial trunk with absence of the left pulmonary artery who was diagnosed at the age of 32 years. Pulmonary vascular disease made the condition inoperable. He does well with medical management after a follow-up of 20 months. PMID- 1428245 TI - Left internal thoracic artery bypass graft in arterial switch with coronary transfer for transposition of the great arteries. AB - The left internal thoracic artery was anastomosed to the circumflex coronary artery to treat myocardial ischemia during an arterial switch procedure for transposition of the great arteries in a 6-month-old infant. Follow-up angiography revealed complete patency of the anastomosis. PMID- 1428246 TI - Assessment of coronary stent by intravascular ultrasound. AB - The use of intravascular ultrasound to assess the adequacy of the deployment of an intracoronary stent is described. Although angiographically a good result was suggested, intravascular ultrasound showed this to be misleading. PMID- 1428247 TI - Exercise-induced bradycardia after Mustard repair for complete transposition. AB - Impairment of sinus rhythm has been reported after the Mustard procedure for complete transposition. We observed two patients who developed severe bradycardia during or after exercise. The first had a 2.8 s sinus pause in the recovery period, the second had a drop in heart rate during exercise. Both eventually had a pacemaker implanted. Exercise testing can be helpful in detecting sick sinus syndrome. PMID- 1428248 TI - Intermediate-term clinical and hemodynamic results of the neonatal arterial switch operation for complete transposition of the great arteries. AB - We prospectively evaluated 49 consecutive hospital survivors of the arterial switch operation for complete transposition and intact ventricular septum by clinical examination, echocardiography, cardiac catheterization, 12-lead and 24-h Holter ECG. The mean length of follow-up was 40 +/- 18 months. Forty-six children are clinically asymptomatic without medication, 2 died due to coronary related left ventricular dysfunction 3 and 12 months after surgery, and 1 required reoperation because of severe bilateral pulmonary branch stenoses. Except for this case, cardiac catheterization (n = 23) revealed a mean gradient of only 17 +/- 8 mmHg between the right ventricle and distal pulmonary arteries. Left ventricular end-diastolic volume was within normal limits except for 2 cases with volumes slightly below normal, the mean ejection fraction was 78 +/- 5%, and end diastolic and end-systolic ventricular shapes were normal. The mean cardiac index was 4.14 +/- 0.69 l/min/m2. Left ventricular end-systolic wall stress to velocity of fiber shortening relation was normal in all cases examined (n = 15), indicating normal myocardial contractility. Significant neoaortic valve insufficiency was never observed despite considerably enlarged aortic roots. Twenty-four-hour Holter ECG records (n = 46) provided no evidence of serious atrial arrhythmias, especially sinus node dysfunction. These encouraging intermediate-term results make the arterial switch operation the treatment of choice at present, for neonates with simple transposition. PMID- 1428249 TI - Social adaptation of young adults with congenital heart disease. AB - The social status of 71 young adults (30 females, 41 males, aged 22.9 +/- 1.9 yr) with congenital heart disease was compared with that of 211 (106 females, 105 males, mean age 23.2 +/- 1.4 yr) randomly selected controls. The clinical examinations included clinical study with ultrasonic visualization, electrocardiography, X-ray and measurement of exercise capacity. In the study group 87% had completed school at the secondary level and another 21% at high school level, while the corresponding figures in the control group were 98% and 51%. About half of both groups continued to vocational training and a fifth to a higher level. Those without any vocational education made up 32% of the study group (95% confidence interval 21-43%) and 11% of the controls (95% confidence interval 7-15%). State benefits were the main source of income for 13% of the study group as compared to 2% among the controls. The employment status of the actual labour force showed no significant difference between the groups. Among patients with congenital heart disease there were significantly more of those who had developed a dependent life style, living with their parents without a marital or quasi-marital relationship. A cyanotic type of severe heart defect is one of the factors predisposing to poor success at school and a dependent lifestyle. Congenital heart disease, even when treated, is a significant factor which influences adult life. The results call for more practical support to assist psychosocial maturation, especially in patients with residual defects. PMID- 1428250 TI - Effect of diltiazem on norepinephrine-induced acute left ventricular dysfunction. AB - The present study has examined the role of diltiazem as a protective agent in a canine model of norepinephrine cardiotoxicity. Effects of diltiazem, 20 micrograms/kg/min x 5 min pretreatment followed by 10 micrograms/kg/min x 90 min, or saline infusion were examined at baseline and 1 h after infusion of norepinephrine, 4 micrograms/kg/min for 90 min, in closed-chest anesthetized dogs. Left ventricular function was assessed by equilibrium radionuclide angiogram and two-dimensional echocardiogram. In 7 saline experiments, hypotension and increased heart rate were observed at 1 h post infusion. In the diltiazem-treated group (n = 7), mean arterial pressure and heart rate were unchanged. In the saline group, left ventricular ejection fraction fell from 0.50 +/- 0.04 to 0.28 +/- 0.04. Left ventricular ejection fraction was unchanged in the diltiazem-treated group: 0.52 +/- 0.03 to 0.55 +/- 0.07. Left ventricular end diastolic volume was increased at 1 h post infusion in saline controls but not in the diltiazem-treated group. Measurement of fractional shortening from two dimensional echocardiograms also indicated left ventricular dysfunction in the saline but not diltiazem-treated groups. Left ventricular end-systolic wall stress following norepinephrine infusion was significantly increased in the saline but not diltiazem-treated groups: 122.7 +/- 18.7 vs 67.6 +/- 19.7 g/cm2, respectively. In dogs receiving saline without norepinephrine infusion, no significant changes occurred over the course of the experiment. Histologic examination showed mild contraction band necrosis in saline controls but not in sham saline dogs. Diltiazem showed intermediate histologic evidence of injury, which was not further quantified. This study suggests that effects of norepinephrine on left ventricular function in the canine model of norepinephrine cardiotoxicity may be largely due to increased wall stress following a prolonged increase in afterload. Diltiazem pretreatment afforded significant protection of left ventricular function. PMID- 1428252 TI - Young infarct patients with single-vessel occlusion do not have an underlying prothrombotic state to explain their coronary occlusion. AB - To determine the importance of a prothrombotic state in the pathogenesis of coronary occlusion in young infarct patients, assessment of risk factor profile and thrombotic tendency was undertaken in 25 young male patients (age less than 45 yr) who were shown at angiography, following myocardial infarction, to have occlusion of a single coronary. Comparison was made with a control group of symptomatic males aged greater than 55 yr, who at angiography had significant disease in two or more coronary arteries (multi-vessel disease control group). At the time of the study more patients in the single-vessel disease study group smoked cigarettes (n = 12) compared to the control group (n = 5) (p less than 0.01). Serum cholesterol and triglycerides were higher, and high density lipoprotein-cholesterol lower, in the single-vessel disease group but the difference reached significance only with the high density lipoprotein cholesterol. Quantitative platelet aggregability was similar in the two groups. Although the level of beta-thromboglobulin, was higher in the single-vessel disease study group the difference was not significant. There were also no significant differences between these groups in levels of fibrinogen, Factor XII and alpha-2 antiplasmin. Patients in the multi-vessel disease group, however, had increased Factor VII levels (p less than 0.01). There were no significant differences between the two groups in fibrinolytic potential or in levels of antithrombin III. Coronary occlusion in the young appears likely to be due primarily to an arterial (plaque) related event as opposed to an abnormal coagulation response to minor arterial plaque damage. PMID- 1428251 TI - The effect of antiplatelet therapy on platelet accumulation after experimental angioplasty in the rabbit iliac model. AB - Antiplatelet therapy is routinely used in balloon angioplasty. Yet recent clinical trials have not shown these agents to reduce the incidence of restenosis. As this might be due to inadequate antiplatelet effect, this study was designed to evaluate the effectiveness of antiplatelet therapy in reducing platelet accumulation immediately after angioplasty. Sixty-six atherosclerotic rabbits underwent angioplasty of a focal (50-99%) iliac stenosis after pretreatment with an antiplatelet drug. The animals were randomly given aspirin (10 mg/kg orally) (n = 10), aspirin (10 mg/kg intravenously) (n = 7), aspirin (10 mg/kg per os) plus dipyridamole (25 mg orally) (n = 8), a thromboxane synthetase inhibitor (GS13080, 1 mg/kg/h intravenously) (n = 9) or heparin (500 U/kg intravenously) (n = 9). Platelet accumulation, determined by 51Cr-labeled platelet counts 30 min after angioplasty disclosed a significant reduction from control (44.1 +/- 51.2 platelets/cm x 10(6)) with intravenous aspirin (3.3 +/- 1.9; p less than 0.007) and the thromboxane synthetase inhibitor CGS13080 (15.1 +/- 16.6, p less than 0.04). Aspirin plus dipyridamole reduced platelet accumulation as well (10.4 +/- 9.8, p = 0.076), while oral aspirin (109.5 +/- 240) and heparin (34.7 +/- 35.5) were ineffective. The results of this study demonstrate that pretreatment with antiplatelet agents can reduce platelet accumulation significantly after experimental angioplasty. However, the wide variability in effectiveness particularly with oral aspirin may have important clinical implications. Further investigation into more effective antiplatelet therapy may help to reduce the incidence of abrupt vessel closure and restenosis. PMID- 1428253 TI - A low plasma selenium is a risk factor for peripartum cardiomyopathy. A comparative study in Sahelian Africa. AB - A specific selenium deficiency is a risk factor for Keshan disease, an endemic cardiomyopathy observed in China. In a Sahelian area of Niger, plasma selenium concentration was measured by neutronic activation and particle induced X-ray emission in 35 black African women with peripartum cardiomyopathy and 36 breast feeding women without cardiac failure as controls. The plasma selenium concentration in patients was lower (48 +/- 25 ng/ml, mean +/- standard deviation) than in controls (77 +/- 16 ng/ml) (P less than 0.0001). Moreover, 40% (14/35) patients with peripartum cardiomyopathy had very low plasma selenium concentrations, below 45 ng/ml, versus none in controls. A low plasma selenium concentration is a risk factor for the Sahelian peripartum cardiomyopathy. PMID- 1428254 TI - Transesophageal echocardiography in adults with a continuous precordial murmur. AB - In order to assess the ability of echocardiography in the detection of intracardiac and extracardiac shunts, we studied 11 patients (aged 22-64 yr) with a continuous precordial murmur using transthoracic and transesophageal echocardiography, and correlated the results with the subsequent angiographic and surgical findings. We found that only in 5 of 6 patients with a patent arterial duct could the continuous flow pattern be detected in pulmonary artery using transthoracic echocardiography, whereas it could be readily and accurately identified by transesophageal echocardiography in all patients. The diameters of the patent arterial duct were also measured and found to be in good correlation with subsequent surgical findings (r = 0.98, p less than 0.05). In 2 patients with a ruptured aneurysm of sinus of Valsalva which originated from the right coronary sinus and perforated into the right ventricle, transesophageal echocardiography gave a better image than transthoracic echocardiography. In 2 patients with coronary artery fistula, the origin and site of drainage of the coronary artery could be imaged using transesophageal echocardiography, but the course of coronary artery fistula was more easily detected by transthoracic echocardiography. In one patient with aortopulmonary window, the defect between ascending aorta and main pulmonary artery could readily be imaged by transesophageal echocardiography. We therefore recommend transesophageal echocardiography when evaluating patients with precordial continuous murmur in whom intracardiac and extracardiac shunts or defects are suspected. PMID- 1428255 TI - Electrophysiology and long-term efficacy of pentisomide in patients with supraventricular tachycardia. AB - The electrophysiologic effects of pentisomide were investigated after intravenous (5 mg/kg) and oral (900-1200 mg three times a day) application in 9 patients with drug refractory atrioventricular nodal tachycardia and 6 patients with orthodromic atrioventricular re-entrant tachycardia. Pentisomide did not change sinus cycle length, effective refractory period of the right ventricle and the atrioventricular node. AH, HV interval, effective refractory period of the right atrium, QRS duration and QTc duration were (p less than or equal to 0.01) increased. Tachycardia cycle length was only increased after intravenous application of pentisomide, antegrade effective refractory periods of the accessory pathways and shortest fully pre-excited R-R intervals during atrial fibrillation were increased after the oral treatment phase (p = 0.054). Intravenous pentisomide prevented tachycardia in 6/9 patients with atrioventricular nodal tachycardia and in 2/6 patients with atrioventricular re entrant tachycardia. If intravenous pentisomide did not prevent induction of the tachycardia, oral pentisomide was not effective either. During long-term follow up 2/7 patients with atrioventricular nodal tachycardia and 1/4 patient with atrioventricular re-entrant tachycardia had a recurrence. Long-term treatment with pentisomide had to be discontinued because of possible side effects in 2 patients. It is concluded, that the electrophysiological effects of pentisomide are similar to those of flecainide and propafenone. PMID- 1428256 TI - Effects of phenytoin on the ventricular tachyarrhythmias of chronic Chagas' disease. AB - The effects of phenytoin on the ventricular tachyarrhythmias of 11 patients with chronic chagasic myocarditis were investigated, and correlated with the serum phenytoin levels. Physical examination, laboratory tests and 24- to 48-h ambulatory electrocardiographic recordings were performed before, during (7-14 days) and after treatment with phenytoin (4-6 mg/kg/day, orally, in three divided doses). Significant (greater than 90%) reduction of couplets, bigeminy and runs of ventricular tachycardia were observed in 50-67% of the patients, whereas the frequency of isolated premature ventricular contractions was significantly (greater than 70%) reduced in only 2 patients (18%). Proarrhythmic activity was not observed and adverse side effects were of mild intensity and usually transient, except in one patient, who developed pruritus and skin rash in the presence of toxic phenytoin serum levels (27 micrograms/ml). It is suggested that phenytoin may be useful for the control of repetitive forms of ventricular tachyarrhythmias in selected patients with chronic chagasic myocarditis. PMID- 1428257 TI - Congenitally corrected transposition of the great arteries associated with hypoplasia of the morphological left ventricle in the setting of atrial situs inversus. AB - Hypoplasia of the morphological left ventricle associated with severe pulmonic stenosis and an intact ventricular septum in the setting of congenitally corrected transposition of the great arteries is a rare lesion. We report the clinical and echocardiographic findings of this lesion in a patient with atrial situs inversus. PMID- 1428258 TI - Electrophysiologic effects of selective B1 adrenergic stimulation in the late phase of myocardial infarct healing. AB - Nonspecific adrenergic stimulation plays an important role in the genesis of ventricular tachyarrhythmias in the postinfarction period. However, the role of selective B1 adrenergic stimulation in the aggravation of reentrant ventricular tachycardia is still poorly understood. The purpose of this investigation was to study the regional electrophysiologic actions and arrhythmogenic effects of the B1 adrenergic agonist dobutamine in a postinfarction canine model. Eleven dogs with 4-week-old anterior wall myocardial infarctions, chronic indwelling intramyocardial electrodes and no inducible sustained ventricular tachycardia at baseline, were studied in the closed-chest state at baseline (control) and during intravenous infusion of dobutamine 10 micrograms/kg/min. Dobutamine caused reductions in the effective and absolute refractory periods in the infarct, peri infarct and noninfarcted regions of the myocardium which were similar in magnitude at each region. With dobutamine, only 1 dog had inducible sustained ventricular tachycardia (polymorphic). No spontaneous arrhythmias were seen. In summary, selective B1 adrenergic stimulation alone does not cause dispersion of myocardial refractoriness and does not cause significant proarrhythmia in the chronically infarcted canine heart. Additional metabolic, electrolyte or ischemic abnormalities may be required for B1 adrenergic stimulation to aggravate arrhythmias in this model. PMID- 1428259 TI - Anaemia in children following cardiac transplantation: treatment with low dose human recombinant erythropoietin. AB - Anaemia is common in children following cardiac transplantation. In a series of 5 children with anaemia beyond the immediate post-operative period one had a hypochromic, microcytic anaemia which corrected with oral iron. The other four had normochromic, normocytic anaemias unresponsive to iron or folate supplementation and associated with inappropriately low levels of erythropoietin. Subcutaneous administration of low dose human recombinant erythropoietin to these four patients resulted in correction of their anaemia. Our findings suggest that erythropoietin deficiency is an important cause of anaemia in transplant recipients and should be sought in cases of anaemia refractory to conventional haematinic therapy. In cases of proven erythropoietin deficiency, treatment with erythropoietin is effective, acceptable to patients and preferable to repeated blood transfusion. PMID- 1428260 TI - Is a parental history of coronary arterial disease in children as discriminating as their lipoprotein profile? Nino Jesus Group. AB - The relationship between hyperlipidemia and a parental history of heart attack and other related disorders was studied in 2224 two- to 18-yr-old children in Madrid (Spain). Children were divided into three groups: those with a parental history of heart attack (first group), a parental history of stroke, hypertension, diabetes mellitus or hypercholesterolemia (second group), and no parental history of disease (third group). The number of children with higher than normal levels of total cholesterol (greater than 200 mg/dl), LDL-cholesterol (greater than 135 mg/dl) and/or apolipoprotein B100 (greater than 75 mg/dl) was significantly higher in the first and second group (positive parental history) than in the third (no parental history). Children and adolescents with a parental history of heart attack (first group) had significantly higher mean levels of total cholesterol and LDL-cholesterol; in the 2- to 13-yr age group a significantly higher level of apolipoprotein B was also found. Children and adolescents belonging to the second group had a significantly higher level of LDL cholesterol, and a significantly higher level of apolipoprotein B was also found in the 2- to 13-yr age group. However, only 15% of children with hypercholesterolemia had a parental history of heart attack or other related disorders. This percentage was 41% when second-degree relatives were included in the family history. We conclude that a parental history is not enough to detect children with an abnormal lipid profile who might be at risk for early development of coronary arterial disease. PMID- 1428261 TI - Balloon angioplasty for native coarctation of the aorta in children and adults: factors determining the outcome. AB - Balloon angioplasty was performed in 46 patients (age 2-40 yr) with discrete native coarctation of aorta. Patients with associated patent ductus arteriosus, aberrant subclavian artery and aneurysms were excluded. The peak systolic gradient across the coarcted segment decreased from 52.1 +/- 18.5 mmHg to 18.6 +/ 14.8 mmHg (p less than 0.001), and the diameter of the coarcted segment increased from 3.6 +/- 1.7 mm/m2 to 9.1 +/- 3.2 mm/m2 (p less than 0.001). Follow up haemodynamic and angiographic studies performed in 21 patients at 13.1 +/- 6.9 months after angioplasty, showed good results in 15 patients. Four patients undergoing haemodynamic study and 4 other patients undergoing noninvasive evaluation were graded as having bad results at follow-up. In 5 of these patients the poor results were due to primary failure of angioplasty in relieving the gradient, and three developed re-coarctation after initial fall in the trans coarctation gradient. Four risk factors were identified on univariate analysis, which were associated with significantly larger residual gradients at follow-up: (1) size of isthmus/size of coarcted segment ratio less than 3.0; (2) size of post-coarctation descending aorta/size of isthmus ratio greater than 1.75; (3) size of coarcted segment after angioplasty/size of coarcted segment before angioplasty ratio less than 2.0; and (4) size of balloon/size of coarcted segment ratio less than 3.0. The presence of one or more risk factors was associated with bad late results. On multivariate analysis the ratio of balloon size/coarcted segment size was found to be the sole independent predictor of the late outcome (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428262 TI - Ventricular late potentials: another expression of cardiotoxicity of cytostatic drugs in children? AB - With the aim of finding a sensitive method to detect early anthracycline-induced myocardial damage ultimately resulting in cardiomyopathy, we studied the occurrence of ventricular late potentials, using a signal averaged electrocardiogram, in 68 children with cancer during or after chemotherapy. Ten (15%) of the children showed late potentials; in addition, patients treated with cytostatic drugs had significantly lower voltages of the last 40 ms of the QRS complex (RMS40) and a longer duration of low amplitude signals in the terminal QRS (LAS) than control patients. The occurrence of late potentials was not significantly correlated with anthracycline therapy or dosage, nor with the presence of echocardiographic abnormalities; in none of the patients we found late potentials during therapy with anthracyclines. We therefore conclude that late potentials are not helpful for early detection of myocardial injury. The occurrence of late potentials, however, does show another expression of cardiotoxicity not specifically related to anthracycline therapy. The occurrence of these late potentials may have prognostic significance with regard to the risk of ventricular arrhythmias during longer follow-up of these patients. PMID- 1428263 TI - Effects of dietary supplementation with fish oil on prostanoid metabolism during acute coronary occlusion with or without reperfusion in diet-induced hypercholesterolemic rabbits. AB - We studied the changes in myocardial and aortic concentrations of prostacyclin and thromboxane A2 during acute coronary occlusion with or without reperfusion in rabbits fed with a cholesterol-enriched diet with or without fish oil supplementation for a short (5 days) or long period (6 weeks). New Zealand white male rabbits were divided into 5 groups: Group I, 15 control rabbits fed with a laboratory standard rabbit chow. In addition to the standard chow, the 4 study groups were treated with cholesterol or fish oil. Group II, 17 rabbits fed with a 1% high cholesterol diet for 5 days. Group III, 16 rabbits fed with a diet containing 1% cholesterol and 10% fish oil for 5 days. Group IV, 17 rabbits fed with the same diet as group II for 6 weeks. Group V, 18 rabbits fed with the same diet as group III for 6 weeks. Each group of rabbits was randomly divided into the coronary occlusion or occlusion-reperfusion mode of experiment. Acute coronary occlusion was induced by ligating the marginal branch of the left circumflex coronary artery for 1 h. Subsequent reperfusion for 4 h was performed in the occlusion-reperfusion rabbits. The aortic tissue above the aortic valve and the ischemic and normal (nonischemic) areas of the left ventricle were excised for the measurement of 6-keto-PGF1 alpha and thromboxane B2 levels by radioimmunoassay. Both during coronary occlusion and occlusion-reperfusion, rabbits showed higher myocardial concentrations of 6-keto-PGF1 alpha and thromboxane B2 in the ischemic area than in the normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428264 TI - Atrial natriuretic factor and concomitant hormonal, hemodynamic and renal function changes after slow continuous ultrafiltration. AB - We treated a patient with refractory biventricular heart failure, dilutional hyponatremia and prerenal azotemia, by means of ultrafiltration. After ultrafiltration, gas exchange and cardiac output improved, with concomitant reduction of systemic and pulmonary vascular resistances. Despite a decrease of right atrial and wedge pressure, atrial natriuretic factor rose and plasma renin activity decreased. PMID- 1428265 TI - Repair of asymptomatic aortic valve disease during other cardiac surgery. AB - Repair of asymptomatic aortic valve disease was performed in 12 patients (9 female, 3 male, mean age 57.5 years) undergoing other cardiac surgery. Stenosis was the predominant aortic valve lesion in 7 (group A) with a mean gradient of 33.4 mmHg and regurgitation of mean grade 1.4 was predominant in 5 (group B). Cusp debridement +/- commissurotomy was performed in 9; commissural resuspension in 6 and repair of cusp perforation in 2. Perioperative transoesophageal echocardiography was used to assess the adequacy of repair in 4 patients. Prospective precordial echocardiographic follow-up is complete (mean 4.3 months). In group A there has been a significant reduction is peak aortic pressure gradient (33.4 vs 22.1 mmHg, p less than 0.05) and in cusp thickness (2.25 to 1.64 mm, p less than 0.05). In group B the degree of incompetence has improved in 3 of the 5 patients. Three patients have worsened valve disease following repair; in all these there was mixed valve disease of rheumatic origin. Aortic valve repair of asymptomatic disease during other cardiac surgery is a feasible technique which does not accelerate the disease process in the short term. Long term follow-up is in progress to assess the prognosis of this preventive intervention. PMID- 1428266 TI - The sensitivity of intracoronary injection of acetylcholine in inducing coronary spasm differs in patients with stable and unstable angina. AB - In an attempt to clarify the role of coronary artery spasm in the pathogenesis of unstable angina, acetylcholine (20 and 50 micrograms) was injected directly into the coronary arteries of 19 patients with unstable effort angina (group 1), 30 patients with unstable spontaneous angina (group 2), and 15 patients with stable effort angina due to coronary artery organic stenosis (greater than or equal to 75%) (group 3). Coronary spasm was defined as severe vasoconstriction (greater than or equal to 90% of luminal diameter) with chest pain and/or ischemic ST segment changes. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in 19 patients (100%) of group 1 and 28 (93%) of group 2 but only 3 (20%) of group 3 (p less than 0.01). When acetylcholine was injected into the left and right coronary arteries separately, multivessel spasm (spasm of both coronary arteries) was induced in 5 of 12 (42%) patients of group 1 and in 9 of 23 (39%) patients of group 2. In contrast, intracoronary acetylcholine did not cause multivessel coronary spasm in any of 15 patients of group 3 (0%). These results suggest that coronary arteries in patients with unstable effort angina as well as spontaneous angina are susceptible to spasm and that coronary artery spasm may be responsible at least in part for the genesis of attacks in these patients. PMID- 1428267 TI - The influence of captopril on intrahospital mortality and duration of hospitalization in Nigerians with congestive heart failure. AB - A retrospective study was undertaken to evaluate the impact of captopril on intrahospital mortality and the duration of hospitalization in Nigerians with congestive heart failure. In 1989 and 1990, the mortality rates were 13.7% and 15.2%, respectively, and it appeared to be reduced to 6.6% in 1991 after the introduction of captopril. There was a significant (p less than 0.001) increase in the proportion of patients with early discharges (less than 10 days hospitalization) following the addition of captopril to the standard antifailure regime in Nigerians. PMID- 1428268 TI - Amiodarone reduces QT dispersion in patients with hypertrophic cardiomyopathy. AB - To compare QT interlead variability (dispersion) in patients who receive a class III antiarrhythmic with those not on antiarrhythmic therapy, we measured QT in all 12 leads of a standard ECG in 24 patients with hypertrophic cardiomyopathy, 12 (50%) of whom were on amiodarone monotherapy and 12 (50%) who were not on amiodarone or other cardioactive medication which could affect QT. Age, functional class, chamber dimension or the degree of left ventricular hypertrophy expressed by maximal wall thickness (21 +/- 5 vs 20 +/- 4 mm; p = NS) was not different between the amiodarone and the non-amiodarone group. Maximal corrected QT (QTc) was greater in patients receiving (488 +/- 25 ms) compared to those not receiving amiodarone (451 +/- 23 ms) (p less than 0.001). However, QTc dispersion defined as the difference of maximum minus minimum QTc was decreased in the amiodarone (48 +/- 10 ms) compared to the non-amiodarone group (78 +/- 17 ms) (p less than 0.001). We conclude that in patients with hypertrophic cardiomyopathy, amiodarone prolongs QTc but reduces QTc dispersion. These results agree with expected changes in ventricular recovery time in patients who receive Class III antiarrhythmic agents and provide further support to the theory that QTc dispersion reflects regional differences in ventricular recovery time. PMID- 1428269 TI - Relationship between stature and coronary heart disease in a German male population. AB - Short stature in men has previously been associated with a higher risk of coronary heart disease. In order to further investigate this observation, the physical characteristics of 4470 German men admitted to the Klinik Roderbirken between 1978 and 1989 with a documented myocardial infarction and with a stenosis greater than or equal to 75% in at least one vessel were compared to those of 711 male controls. Results indicated that the myocardial infarct group was significantly shorter by 1.8 cm than the control group (p less than 0.001). However, discriminant function analysis indicated that height accounted for only 1% of the variance between the cardiac and control patients. Classification analysis further indicated that on the basis of height, the percentage of subjects correctly classified for grouping was no better than 54% for the myocardial infarct patients and 57% for the controls. It was concluded that height exerted a minimal influence on coronary heart disease in this population. PMID- 1428270 TI - Transoesophageal Doppler pulmonary venous flow pattern and left atrial spontaneous contrast in mitral stenosis. AB - The relationship between transoesophageal Doppler pulmonary venous flow pattern and spontaneous left atrial contrast was studied in 23 patients with isolated severe mitral stenosis (mitral valve area = 0.8 +/- 0.2 cm2). The patients with none or minimal (1+) spontaneous contrast (n = 15, group I) were compared with those with significant spontaneous contrast (grade 2+, n = 8, group II) with regard to peak systolic velocity (33 +/- 14 cm/s vs 28 +/- 12 cm/s, p = NS), peak diastolic velocity (36 +/- 14 cm/s vs 28 +/- 8 cm/s, p = NS) and peak atrial reversal velocity (19 +/- 4 cm/s vs 19 +/- 8 cm/s, p = NS), systolic forward flow velocity time integral (3.37 +/- 1.73 cm vs 2.78 +/- 0.9 cm, p = NS), diastolic forward flow velocity time integral (2.85 +/- 1.2 cm vs 2.65 +/- 1.87 cm, p = NS), ratios of peak systolic and diastolic velocity (0.91 +/- 0.21 vs 0.95 +/- 0.29, p = NS) and duration of diastolic deceleration (117 +/- 59 ms vs 132 +/- 106 ms, p = NS). The results show that the occurrence of spontaneous contrast in the left atrium in patients with mitral stenosis is not related to the Doppler estimated pulmonary venous flow. PMID- 1428271 TI - Discordance between abdominal and atrial arrangement in a case of complex congenital heart disease. AB - The report describes a rare case of a complex congenital heart disease wherein the splenic status and the relationship of the suprarenal abdominal great vessels strongly suggested right isomerism, but atrial morphology demonstrated usual atrial arrangement. It emphasises the increasing recognition that the arrangement of the abdominal organs need not accurately reflect atrial arrangement. PMID- 1428272 TI - The syndrome of absent or faint second heart sound, rapid systole and forward collapsing pulse. AB - A syndrome consisting of an absent or faint second heart sound, prominent cardiac impulse and non-regurgitant or forward collapse of the pulse is described. There was, moreover, no second sound or flow murmur audible in either the aortic or the pulmonary area even though the impulse and collapsing pulse suggested a hyperdynamic circulation; the upstroke was sharp but without the full waterhammer knock. It is argued that the dominant cause of the collapsing pulse will usually be vasodilation, that absence or faintness of the second sound is due to a narrow angle of divergence between the ventricular and arterial pressure decay curves, and that in marked contrast to aortic regurgitation the quality of the impulse derives from rapid systole of lightly loaded ventricles. Although they described its separate elements, pre-homeostatic era clinicians may have overlooked the syndrome in the belief that the heart regulated a largely passive circulation, regarding only primary intracardiac events and the first heart sound as important. Sir William Stokes nevertheless foresaw that alterations in the second sound might be due to changes in vascular tone as well as in elasticity. Wider recognition, deeper understanding and appropriate correction of this syndrome may prove both useful and enlightening. PMID- 1428273 TI - A case of multiple pericardial hydatid cysts. AB - Pericardial cysts are rare developmental benign intrathoracic lesions and constitute 7% of all mediastinal tumors. As many as 70% of the cysts are found in the right cardiophrenic angle. Unusual locations include the left costophrenic angle, the hilum and the superior mediastinum at the level of the aortic arch. Cysts arising inside the pericardial cavity and attached to the heart are exceedingly rare. We describe a case of multiple pericardial hydatid cysts. PMID- 1428274 TI - Ventricular septal aneurysm in a case of Ehlers-Danlos syndrome. AB - Cardiac abnormalities are a recognised feature of connective tissue disorders. We report a case of Ehlers-Danlos syndrome associated with an aneurysm of the membranous ventricular septum and mitral valve prolapse. To our knowledge this is the first reported association of Ehlers-Danlos syndrome and ventricular septal aneurysm. PMID- 1428275 TI - Aschoff node histogenesis. PMID- 1428276 TI - Infective endocarditis after balloon mitral dilatation. PMID- 1428277 TI - Mechanism of cyanotic spells in tetralogy of Fallot--the missing link? AB - The mechanism of cyanotic spells in patients with tetralogy of Fallot is not clear. Increases in infundibular contractility or hyperpnoea have been considered as the key factors, but this explanation appears inadequate. In this review, arguments are presented against these commonly held views. Preliminary evidence is synthesised in favour of another more plausible hypothesis that cyanotic spells may result from mechanoreceptor stimulation from the right ventricle. Increased contractility (due to catecholamines) and decreased right ventricular size (due to various factors) can trigger a reflex resulting in hyperventilation, some peripheral vasodilation without bradycardia, and this may initiate a spell. This mechanism explains most of the precipitating events and many other issues about cyanotic spells more satisfactorily. PMID- 1428278 TI - Hypertrophic cardiomyopathy and myocardial bridging. AB - Two patients are reported in whom hypertrophic cardiomyopathy was associated with myocardial bridging of the left anterior descending coronary artery. One had a history of angina and recurrent syncope, the other had chest pain and exertional dyspnoea. In each case the diagnosis was made by cross-sectional echocardiography and coronary angiography. PMID- 1428280 TI - Giant epicardial lipoma. AB - A patient undergoing coronary artery bypass was found to have a giant epicardial lipoma weighing 1.36 kg which was excised uneventfully. The radiological and pathophysiological features are considered, and the options for management discussed. PMID- 1428279 TI - Mycotic aneurysm of the descending aorta diagnosed by echocardiography. AB - We present a 3-yr-old girl with coarctation of aorta and patent ductus arteriosus in whom mycotic aneurysm and bacterial endarteritis developed postoperatively and was diagnosed by two-dimensional and Doppler echocardiography. Five weeks after the operation of ligation of ductus and resection of coarctated segment, the patient was readmitted with complaints of vomiting, fever and coughing. Bacterial endarteritis, empyema and septic arthritis were diagnosed. Suprasternal echocardiographic examination demonstrated an aneurysmatic appearance 60 x 65 mm in size at the location of coarctation. The patient died, most probably due to aortic rupture, before surgical treatment could be undertaken. Autopsy study confirmed our diagnosis. PMID- 1428281 TI - Radiofrequency ablation of incessant ventricular tachycardia to prevent multiple defibrillator shocks. AB - In a patient who received frequent shocks from an implantable defibrillator, a slow ventricular tachycardia originating in a large left ventricular aneurysm was ablated with radiofrequency current. Pacemapping perfectly matched the spontaneous, incessant arrhythmia. Local entrainment was present, along with a mid-diastolic potential of 65 microV. Application of 30 W terminated tachycardia within 12 s. He had no more recurrences during follow-up. PMID- 1428283 TI - Powerful hemodynamic determinants of left ventricular mass. PMID- 1428282 TI - Recurrent acute myocardial infarction during sport. AB - A 48-yr-old well conditioned man developed acute myocardial infarction twice during sporting activities. After both events right coronary angiography showed a moderate proximal stenosis and, 5 months later, a subtotal obstruction at the site of prior slight lumen irregularity. This case suggests a causal relationship between sport and the occurrence of acute coronary events. PMID- 1428284 TI - It is still controversial which is the correct way to report and to interpret event rates of clinical trials. PMID- 1428285 TI - Lung function in atrial septal defect after heart surgery. AB - Lung volume, indices of lung elasticity and airway patency were measured in 74 patients, 9-21 yr old (15.0 +/- 2.5 yr) with atrial septal defect (secundum type) from 2-11 (5.1 +/- 2.5) yr after successful surgical correction. Clinical condition in all patients was classified as excellent. Heart surgery was performed at the age of 4-14.8 (9.9 +/- 3.0) yr. Lung function abnormalities were found in 35 (47.3%) patients. Lung recoil pressure was significantly increased in 24 (32.4%) patients. The mean value of lung recoil pressure at 100% of total lung capacity reached 123 +/- 31% of the predicted value (P < 0.0001). Specific static compliance was within normal limits. Specific airway conductance was significantly reduced in 13 (17.6%) patients. Maximum expiratory flow at 25% of vital capacity was significantly reduced in 4 (5.4%) patients. Static lung volumes did not differ from reference values. Since various abnormalities of lung function tests (most frequently the tests suggested increased lung stiffness and obstruction of larger airways) were revealed in almost half of the studied children and adolescents after successful surgery for atrial septal defect, we propose to carry out lung function tests routinely as another criterion of health conditions in these patients. PMID- 1428286 TI - Marked alternans of the elevated ST segment during occlusion of the left anterior descending coronary artery in percutaneous transluminal coronary angioplasty: clinical background and electrocardiographic features. AB - To investigate the clinical background and the electrocardiographic features of marked alternans of the elevated ST segment during coronary angioplasty, we examined 12-lead electrocardiograms recorded continuously during occlusion of the left anterior descending coronary artery by balloon inflation in 41 patients. The incidence of marked ST alternans was 27% of 41 patients and 15% of 117 balloon occlusions. The incidence decreased progressively from the first to the third occlusion. The time course of ST alternans was determined. Compared with patients without ST alternans, patients with ST alternans had a shorter history of angina, less severe stenosis of the target lesion before coronary angioplasty, more leads showing ST elevation during occlusion, higher ST elevation during occlusion and lower incidence of previous myocardial infarction in the left anterior descending coronary arterial area. ST alternans recorded on the surface electrocardiogram may thus be considered a marker of acute severe and extensive myocardial ischemia. PMID- 1428287 TI - Percutaneous transluminal coronary angioplasty in patients more than 75 years old: early and long-term results. AB - Over 4 yr, 102 consecutive patients more than 75 yr old (56 men, 46 women; mean age 78 +/- 3 years, range: 76-89 years) underwent 120 percutaneous transluminal coronary angioplasty procedures. At baseline, 86% had severe anginal symptoms (Canadian class III or IV), 43% had a history of prior myocardial infarction; 61% had multivessel coronary artery disease, and mean left ventricular ejection fraction was 60 +/- 11%. Calcifications were observed on 66% of the dilated arteries. A total of 158 vessels (1.3 vessel per procedure) were attempted: 1 vessel in 89 procedures (74%), 2 vessels in 24 (20%) and 3 vessels in 7 (6%). The primary success rate was 80% per lesion (126/158) and 77% per procedure (92/120). Complications included 3 deaths (3%), 9 Q-wave infarctions (7.5%) and there was no emergency coronary bypass surgery. The primary success rate was significantly related to the absence of coronary calcifications on the dilated segment (88% versus 75%, p < 0.05) and to the initial patency of the dilated artery (subtotal stenosis: 83% versus total occlusion: 53%, p < 0.05). Follow-up data were obtained in the 79 consecutive patients with a duration of follow-up exceeding 8 months. The mean duration of follow-up was 23 +/- 13 months (range 8 to 61 months). No patient was lost to follow-up; 11 patients died (cardiac causes: 7), 2 had a non-fatal infarction, 7 had aortocoronary bypass surgery and 18 had repeat percutaneous transluminal coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428288 TI - Electrophysiological abnormalities of the atrial muscle in patients with sinus node dysfunction without tachyarrhythmias. AB - The duration and the number of fragmented deflections of the right atrial electrograms were assessed and quantitatively measured in 74 patients who underwent endocardial catheter mapping during sinus rhythm. The bipolar electrograms were recorded at 12 sites in the right atrium. An abnormal atrial electrogram was defined as a duration of 100 ms or longer, and/or 8 or more fragmented deflections, according to our previous criteria. The patients were divided into two groups. The control group consisted of 41 age-matched patients with normal sinus node function and without paroxysmal atrial fibrillation. The study group comprised 33 patients with sinus node dysfunction but without tachyarrhythmias. Abnormal atrial electrograms were observed in 8 (19.5%) control patients, and in 16 (48.5%) sinus node dysfunction patients; p < 0.02. The total number of abnormal electrograms was 14 (2.89%) of 483 atrial electrograms in controls, and 36 (9.38%) of 384 in the study group; p < 0.0002. The mean duration (75.6 +/- 17) and the mean number of fragmented deflections (4.1 +/- 2) of the total atrial electrograms in the sinus node dysfunction group was significantly greater than that in controls (70.9 +/- 11 and 3.6 +/- 1, respectively); p < 0.01. The mean number of abnormal electrograms per patient in the study group (1.06 +/- 1.8) was significantly higher than that in the control group (0.3 +/- 0.8); p < 0.05. These data suggest that: (1) there is a significantly greater electrophysiological abnormality of the atrial muscle in patients with sinus node dysfunction but without paroxysmal atrial fibrillation than in age-matched controls, and (2) not only the sinus node but also the atrial muscle is electrophysiologically altered in patients with sinus node dysfunction but without tachyarrhythmias. PMID- 1428289 TI - Reappraisal of electrical cure of atrioventricular nodal reentrant tachycardia- lessons from a modified catheter ablation technique. AB - A modified catheter ablation technique was studied prospectively in 29 patients with atrioventricular (AV) nodal reentrant tachycardia. A His bundle electrode catheter was used for mapping and ablation. Cathodic electroshocks (100-250 J) were delivered from the distal two electrodes (connected in common) of the His bundle catheter to the site selected for ablation. The optimal ablation site recorded the earliest retrograde atrial depolarization, simultaneous or earlier than the QRS complex, with absence of a His bundle deflection during AV nodal reentrant tachycardia. One additional electrical shock was delivered if complete abolition of retrograde VA conduction persisted for more than 30 min and AV nodal reentrant tachycardia was not inducible during isoproterenol and/or atropine administration. With a cumulative energy of 323 +/- 27 J and a mean of 2.3 +/- 0.5 shocks interruption or impairment of retrograde nodal conduction was achieved. Antegrade conduction, although modified, was preserved in 27 patients, with persistence of complete AV block in 2 patients. Two of the 27 patients still need antiarrhythmic agents to control tachycardia, the other 25 patients were free of tachycardia within a mean follow-up period of 13 +/- 2 months (range 7 to 20 months). Twenty-three patients received late follow-up electrophysiological studies (3-6 months after the ablation procedures), and the AV nodal function curves were classified into 4 types. The majority of the patients (15/23) had loss of retrograde conduction. Among the 8 patients with prolongation of retrograde conduction, 4 patients still had antegrade dual AV nodal property but all without inducible tachycardia. In conclusion, preferential interruption or impairment of retrograde conduction was the major, but not the sole, mechanism of electrical cure of AV nodal reentrant tachycardia. PMID- 1428290 TI - Alterations in cardiac diastolic function in patients with ankylosing spondylitis. AB - Ankylosing spondylitis is associated with a decreased survival that appears attributable to cardiovascular causes. To determine whether alterations in systolic or diastolic cardiac function precede overt cardiac disease, 20 ankylosing spondylitis patients without clinical evidence of cardiovascular disease and 25 healthy age and gender matched controls were studied by cross sectional and Doppler echocardiography. Systolic function was assessed by wall motion analysis and ejection velocities. Diastolic function was measured by the peak velocity of early ventricular inflow, peak velocity in late diastole during atrial systole, the ratio of these velocities and the diastolic filling time. Atrial, ventricular and aortic dimensions were similar in patients and controls. Ejection indexes and systolic wall motion were normal in both groups. Diastolic function differed in patients as evidenced by a shorter diastolic filling period [405 +/- 68 ms vs 548 +/- 136 ms, p = 0.0001], a reduced velocity of early mitral inflow [0.55 +/- 0.09 m/s vs 0.63 +/- 0.11 m/s (p = 0.005)], and lower ratios of early/late inflow velocities [1.21 +/- 0.33 vs 1.60 +/- 0.35 (p = 0.0005) for mitral and 1.36 +/- 0.34 vs 1.71 +/- 0.42 (p = 0.016) for tricuspid]. These changes are consistent with impaired ventricular relaxation in some patients with ankylosing spondylitis. PMID- 1428291 TI - Cardiopulmonary exercise testing early after catheter-balloon mitral valvuloplasty in patients with mitral stenosis. AB - Seven female patients (age 27 to 53 yr) with significant mitral stenosis performed continuous, incremental, maximal treadmill exercise tests the day before and within 3-5 days after catheter-balloon valvuloplasty. Mitral valve area determined by the echo-Doppler method increased from 0.9 +/- 0.3 cm2 to 1.9 +/- 0.7 cm2 (p < 0.02). Mean left atrial pressure was reduced from 24 +/- 8 to 13 +/- 7 mmHg (p < 0.01) and mean pulmonary artery pressure from 36 +/- 13 to 28 +/- 10 mmHg (p < 0.02) with a non-significant increase in cardiac output from 3.6 +/- 1.2 to 4.0 +/- 1.7 l/min. After catheter-balloon valvuloplasty all patients reached a higher maximal workload during exercise, and mean value of oxygen consumption and pulmonary ventilation were significantly lower in submaximal workloads. The calculated ventilatory equivalent for oxygen was significantly reduced in submaximal and in maximal workloads after catheter-balloon valvuloplasty. Peak oxygen consumption and the ventilatory anaerobic threshold were not changed after catheter-balloon valvuloplasty (pre 15.59 +/- 2.72 vs post 16.90 +/- 3.44 and pre 12.10 +/- 2.55 vs post 12.62 +/- 2.71 ml/kg/min, respectively). We concluded that after catheter-balloon valvuloplasty the cost of breathing was reduced and the oxygen consumed was more effectively utilized during exercise. Increases in peak oxygen consumption and in ventilatory anaerobic threshold would require circulatory and metabolic adaptations in response to increased physical activity and were not observed when cardiopulmonary tests were performed early after catheter-balloon valvuloplasty. PMID- 1428292 TI - Doppler echocardiographic determination of aortic and pulmonary valve orifice areas in normal adult subjects. AB - Cross-sectional and Doppler echocardiography were performed in 36 healthy adult subjects (aged 19 to 50 yr, mean 28 +/- 9; male 23, female 13) to establish normal values for aortic and pulmonary valve orifice areas. Standard continuity equation using echo-determined ventricular outflow tract diameters and Doppler determined flow-velocity integrals from the outflow tracts and the corresponding great arteries, was employed to calculate the valve areas. Mean left ventricular outflow tract diameter was 1.92 +/- 0.17 cm (range 1.5-2.3 cm) and right ventricular outflow tract diameter was 1.80 +/- 0.18 cm (range 1.5-2.2 cm). Calculated aortic valve orifice area was 2.63 +/- 0.31 cm2 (1.76 +/- 0.2 cm2/m2) and correlated poorly with body surface area (r = 0.31, p > 0.05). Mean pulmonary valve orifice area was 3.01 +/- 0.36 cm2 (2.02 +/- 0.20 cm2/m2) and had a modest correlation with body surface area (r = 0.38, p < 0.05). No difference was observed between males and females for indexed aortic and pulmonary valve orifice areas. These data provide normal values for echocardiographically determined semilunar valve orifice areas and question the practice of indexing valve area for body surface in adult subjects. PMID- 1428293 TI - Surgical pathology of the mitral valve: gross and histological study of 1288 surgically excised valves. AB - A consecutive series of 1288 mitral valves surgically excised from 1981 through 1989 were studied macroscopically and histologically. The explanted valves were affected by: chronic rheumatic disease (1179, 91.5%), floppy mitral valve (84, 6.5%), bacterial endocarditis (19, 1.5%), and post-ischemic mitral incompetence (6, 0.5%). Among 1179 post-rheumatic cases, mixed mitral stenosis and incompetence was the most frequent malfunction (747, 58%). Isolated mitral incompetence was diagnosed in 72 (6.11%) cases only, and isolated stenosis in 360 cases. In 52 valves, excised because of chronic rheumatic disease, the histology showed unexpected signs of acute rheumatism of the leaflets and the papillary muscles. In these patients clinical symptoms and blood tests were negative for rheumatic disease. Mitral incompetence, possibly due to papillary muscle dysfunction, was the prevalent lesion (61.5%). A total of 181 patients (14.05%) with pure mitral incompetence underwent surgery. In 84 patients (46.4%), the floppy mitral valve was the most frequent cause of valve dysfunction, 72 (39.8%) had rheumatic disease, 19 (10.5%) infective endocarditis, and 6 (3.4%) ischemic heart disease. In the group with floppy mitral valve, males were more prevalent than females (51:33). The mean age of the 4 patients with Marfan's syndrome and non-Marfan patients was noticeably different (17 vs 49 yr). Moreover leaflet deformation, tendinous cord elongation and annulus dilatation were the most common causes of valve incompetence. Floppy mitral valve and infective endocarditis were the cause of cordal rupture in 43.5% of the cases. This was a severe complication which always required emergency surgery. PMID- 1428294 TI - Comparison of acute and steady-state conditions of gallopamil therapy in stable angina pectoris. AB - We studied 12 patients with stable effort angina in a randomized, double-blind, cross-over and placebo-controlled trial to compare the different antianginal efficacy of "acute" and "chronic" (after reaching a steady-state level) gallopamil therapy. Efficacy was assessed using treadmill exercise testing (Bruce protocol) after a 50 mg single-dose and at the end of a nine-dose course of 50 mg of gallopamil (given three times a day). Three daily exercise tests were performed the first, second, fifth and eighth day of the study protocol at 8, 12 and 16 h. Four hours after a single-dose of gallopamil 50 mg both angina-free exercise time and time to 1 mm ST segment depression increased by a mean value of 78 s (p < 0.003) and 53 s (p < 0.03), respectively, with respect to placebo values. Under steady-state conditions exercise time and time to 1 mm ST segment depression increased by a mean value of 59 s (p < 0.009) and 46 s (p < 0.015), respectively, 4 h after the last dose. The duration of the anti-ischemic effects was no longer present after 8 h for both treatment schedules. Furthermore no significant differences were observed on parameters of ischemia after a single dose as compared to "chronic" therapy. The results of this study reveal that, in accordance with the pharmacodynamic properties of the drug, the anti-ischemic efficacy of 50 mg of gallopamil remains for approximately 4 h. Reaching a steady state condition does not imply a prolongation of the anti-ischemic effect. PMID- 1428295 TI - Pharmacokinetics and pharmacodynamics of prednisolone after intravenous and oral administration. AB - The pharmacokinetics and pharmacodynamics of prednisolone were investigated according to four different routes of administration: 20 and 40 mg prednisolone orally in the morning, 20 mg prednisolone orally in the evening and 40 mg prednisolone intravenously in form of prednisolone phosphate in the morning. The plasma levels of prednisolone were followed using HPLC. To study the pharmacodynamics of prednisolone, glucose levels and various blood cell parameters such as erythrocytes, leukocytes, segmented neutrophilic granulocytes, eosinophils, basophils, monocytes and lymphocytes were followed. To summarize the data, the area under the effect-time-curve (AUCE) was calculated by the trapezoidal rule. The results show that the pharmacokinetics of prednisolone is dose-dependent (non-linear) and time-dependent. Prednisolone concentrations in plasma after a 20 mg and 40 mg dose are very similar, indicating that the pharmacokinetics of prednisolone are non-linear and dose-dependent with a higher clearance for higher concentrations. The comparison of 20 mg administered in the morning with the same dose given in the evening shows that the pharmacokinetics of prednisolone after oral administration of equal doses changes during the day with higher concentrations in the morning than in the evening. Furthermore, the results of the present study confirm the presence of pharmacodynamic corticosteroid effects on blood cell count and blood glucose. No statistically significant differences were observed for the four different treatments. In summary, it can be concluded that due to the complex pharmacokinetics of prednisolone, it is difficult to make accurate predictions of the expected effect time relationships. PMID- 1428296 TI - A comparative study of free plasma choline levels following intramuscular administration of L-alpha-glycerylphosphorylcholine and citicoline in normal volunteers. AB - L-alpha-glycerylphosphorylcholine (alpha-GPC) is a recently developed cognitive enhancer whose mode of action is considered to involve the release of free choline, which is then utilized for acetylcholine and phosphatidylcholine biosynthesis in the brain. The purpose of this study was to evaluate the profile of free plasma choline levels following a single i.m. dose of alpha-GPC in 12 normal volunteers. Citicoline (CTC), which also acts as a choline precursor, was included for comparison purposes. Each subject was studied on three randomized occasions, (i) in a control day in the absence of drug administration (to evaluate the plasma level profile of endogenous choline), (ii) after i.m. alpha GPC (1,000 mg) and (iii) after i.m. CTC (1,000 mg) respectively, with a wash-out period of at least 1-week between sessions. Blood samples for plasma choline HPLC determinations were collected at regular intervals over a 6 h period. In the control session, plasma choline levels remained stable during the sampling period. The administration of alpha-GPC was associated with a rapid rise in plasma choline, peak levels being usually observed at the first (0.25 h) or second (0.5 h) sampling time after the injection. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of CTC, plasma choline levels showed a similar time course but were considerably lower than those observed after the administration of alpha-GPC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428298 TI - Professional role of the clinical pharmacologist. AB - The position of clinical pharmacologists in the field of medicine is reviewed. In more than one-third of the medical schools in Europe, teaching of clinical pharmacology is inadequate or non-existent. The situation in Italy is even worse; there are, however, 18 schools of specialization in pharmacology in that country, covering four areas, clinical and applied pharmacology, toxicology and chemotherapy with the course lasting four years. In addition there are 13 hospitals at regional level which provide service in clinical pharmacology, though in most of these the clinical pharmacologist has no direct clinical responsibilities. Three basic requirements, accepted by the College of Italian Pharmacologists, are listed aimed at obtaining official recognition of the professional role of a physician specialized in clinical pharmacology. PMID- 1428297 TI - A simple useful method for the determination of hepatic function in patients with liver cirrhosis using caffeine and its three major dimethylmetabolites. AB - Serum concentrations of caffeine (CA) and its three major dimethylmetabolites (theobromine; TB: paraxanthine; PX: theophylline; TP) were measured in fifteen patients with cholelithiasis, in ten patients with cirrhosis and in ten healthy subjects after the oral CA (2 mg/kg) loading. The correlations of total body clearance (CL) between three-point study (sampling times 1, 2 and 4 h) and nine point study (sampling times 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 h) were highly significantly correlated (r = 0.988, p less than 0.001). The elimination half life (t1/2) of CA was significantly longer in cirrhotic patients than in the other two groups. Cirrhosis had no effect on the apparent volume of distribution (Vd) of CA, but CL of CA was substantially reduced in these patients. Production of the three metabolites of CA, but mainly PX, was reduced in patients with cirrhosis. There were significant correlations between the serum PX/CA (r = 0.911, p less than 0.001) and (PX + TB + TP)/CA (r = 0.905, p less than 0.001) ratios and CL of CA at 4 h after CA administration in the three groups. These findings suggest that CA pharmacokinetic parameters can be estimated using a simplified three-point blood sampling procedure following a single oral load and that the serum PX/CA or (PX + TB + TP)/CA ratio in a single blood sample taken 2 or 4 h after dosing provides a useful indicator for the assessment of hepatic drug-oxidizing capacity, N-demethylation, in decompensated liver cirrhosis. However, CA test was unable to distinguish the difference of liver function between the control subjects and in patients with cholelithiasis. PMID- 1428299 TI - Establishing requirements for the use of terms for reporting adverse drug reactions. AB - The establishment of a project for the standardization of international reporting of adverse drug reactions (ADR), sponsored by the Council for International Organizations of Medical Sciences is described. The need to establish requirements for properly diagnosing a given suspected ADR and to describe it with the correct terms is demonstrated. However in view of the difficulties involved, it is suggested that the present deliberate approach needs to be reconsidered. PMID- 1428300 TI - Efficacy and tolerability of medium-term treatment with simvastatin in primary hypercholesterolaemia. AB - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, a new class of hypolipidaemic agents, have been recently shown to be effective in lowering both total and low-density lipoprotein (LDL)-cholesterol. In the present study 20 patients were treated with simvastatin for six months. Various dosing regimens of 10, 20, and 40 mg/day were employed. Administration of simvastatin 10 to 40 mg/day resulted in a 24.7 to 35.8% reduction in LDL-cholesterol levels and in a 19.5 to 26.9% decrease of total cholesterol levels. Moreover, simvastatin increased high-density lipoprotein-cholesterol and induced a decrease in plasma triglycerides. The side-effect profile was similar to other observations and included reversible transaminase elevations, myalgia and gastrointestinal complaints. From the present study simvastatin seems to be well tolerated in the short- to medium-term and to be effective; however, its long-term tolerability needs to be confirmed. PMID- 1428301 TI - Effect of midecamycin acetate on gastrointestinal motility in humans. AB - The effect was studied on gastrointestinal motor activity of three different macrolides (erythromycin, roxithromycin and midecamycin acetate), administered by mouth in therapeutic doses. This placebo-controlled study was performed in 12 normal human subjects by means of intraluminal pressure measurements in the gastric antrum, duodenum and upper jejunum. In each subject, three manometries were done for 5 h in the interdigestive period and for 3 h postprandially. In the interdigestive period, midecamycin acetate did not affect the characteristics of the gastric migrating motor complex (MMC) and did not increase the number of antral contractions or the gastric motility index as compared to the placebo. Erythromycin and roxithromycin increased the number of antral contractions (24.5 +/- 11 versus 15.2 +/- 7 and 28.4 +/- 12 versus 14.9 +/- 5.9 respectively) and the motility index (4.05 +/- 0.5 versus 3.17 +/- 0.6 and 4.38 +/- 0.2. versus 3.64 +/- 0.7 respectively) as compared to the placebo. In the postprandial period, the number of antral contractions was not significantly increased by any of the three antibiotics. The postprandial antral motility index was not significantly increased by midecamycin acetate. In contrast, the postprandial antral motility indexes after erythromycin (4.4 +/- 0.5) and after roxithromycin (4.3 +/- 0.2) were significantly greater than after the placebo. In the upper small intestine, erythromycin elicited an increased number of phase-III-like activity events and roxithromycin shortened the MMC cycle length. Midecamycin acetate had no effect on interdigestive upper jejunal motility. The postprandial jejunal motor activity was not altered by any of the three antibiotics neither during the interdigestive nor the postprandial periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428302 TI - Effects of calcium channel blockers on cardiovascular responses to smoking in normotensive and hypertensive smokers. AB - To evaluate the effects of short- and long-term administration of calcium (Ca) entry blockers on cardiovascular responses to cigarette smoking, 28 normotensive and 26 hypertensive smokers were studied. According to a double-blind, cross-over design, normotensive smokers were given a single dose (10 mg) of isradipine or a placebo and were checked before and after dosing. After a four-week period on a placebo, hypertensive smokers were treated with slow-release nicardipine 40 mg twice daily for six months and were checked at the end of the placebo period, after the first dose of nicardipine and at the end of six months of therapy. In both groups, blood pressure and heart rate were monitored by a Takeda TM 2420 non invasive device every 3 min for 2 h. During the first hour patients were not allowed to smoke, during the second hour they were asked to smoke one cigarette every 15 min. In both normotensive and hypertensive smokers, calcium entry blockers produced a significant attenuation of the rise in blood pressure induced by cigarette smoking. Such effect was more evident after long-term therapy. Acceleration of the heart rate due to smoking was not significantly affected by the administration of Ca-antagonists, although a tendency towards a lesser heart rate increase was observed, particularly after long-term treatment. It was concluded that calcium entry blockers, reducing blood pressure variability, which bears a positive relationship with target organ damage, might be useful in the treatment of hypertensive smokers who were unwilling or unable to stop smoking. PMID- 1428303 TI - Metabolic aspects of acute cerebral hypoxia during extracorporeal circulation and their modification induced by acetyl-carnitine treatment. AB - Following their previous research experiences in human tissue hypoxia, in the present study the authors. investigated the metabolic effects of acute brain hypoxia in a group of patients in course of extracorporeal circulation for aorto pulmonary bypass. One hundred subjects were treated, half with a placebo and half with acetyl-carnitine to evaluate the effects of oxidative stress in some brain plasmatic metabolites and to verify the effect of acetyl-carnitine on the tissue energy capacity. The levels of lactate, pyruvate, succinate and fumarate showed a significant imbalance due to hypoxia, while the acetyl-carnitine treatment confined the metabolic gradients within physiological limits. This means that during the course of extracorporeal circulation brain hypoxia plays a pathological role assuming the typical picture of cellular oxidative damage and the acetyl-carnitine antagonizes these deleterious effects of hypoxia by a protective mechanism on the energy processes and then on the cellular enzymic activities. In this regard, the d-tyrosine levels, considered as a proteolytic index, confirm the action of acetyl-carnitine on the cell morpho-functional integrity. PMID- 1428304 TI - Combined therapy with cyclobenzaprine and ibuprofen in primary fibromyalgia syndrome. AB - Non-steroidal antiinflammatory drugs are not very effective, even if commonly used, in primary fibromyalgia syndrome (PFS), whereas cyclobenzaprine (C) has proved to be quite useful. The aim of this open randomized study was to compare low-dose C alone or in combination with ibuprofen (I) in 32 female patients suffering from PFS. Fifteen patients were given C 10 mg, and 17 patients C 10 mg plus I 600 mg. All patients received the drugs orally at night and were evaluated at baseline and at days 5 and 10. Assessment of efficacy included the number of tender points (max. = 16), muscle tightness (score 1-5), sleep difficulty (score 1-10), pain intensity (visual analogue scale 0-10) and duration of morning stiffness (min). At the end of the study all symptoms were found to be improved to the same extent in both treatment groups. An exception was morning stiffness, which became significantly more reduced in the patients taking C plus I. No patient discontinued the trial owing to adverse side-effects. In conclusion, C and I given concomitantly at night proved to be safe and advantageous in relieving the discomfort of PFS in the short term. PMID- 1428305 TI - Subchondral vascularisation and osteoarthritis. AB - A prospective experiment was carried out in 40 rabbits in which the blood supply to the patella was interrupted for defined periods from 2 weeks to 6 months. With prolonged ischaemia, there were clear changes in the articular cartilage which were comparable with those seen in human osteoarthritis. PMID- 1428306 TI - Histological examination of surface repair tissue after successful osteotomy for osteoarthritis of the hip joint. AB - In this study biopsy specimens of the surface repair tissue from the weightbearing area of the hip joint were collected from 15 patients who had undergone successful valgus osteotomy, and these were examined histologically. In 6 of the 15 patients the specimens stained strongly with safranin-O in all three layers of the matrix. However, the repair tissue from another 6 patients showed strong staining only in the intermediate and deep layers, while that from 2 patients stained only in the deep layer. Specimens from 5 patients were stained for S-100 protein and positive cells were detected in all cases, demonstrating that the cells in the repair tissue were chondrocytes. However, there was no tide mark in the repair tissue and the arrangement of the cells differed from that in normal cartilage. Discontinuity of the subchondral bone was also noted. These findings make it likely that the repair tissue was of bone marrow origin. PMID- 1428308 TI - Osteochondritis dissecans patellae. Is there a genetic predisposition? AB - The aetiology of Osteochondritis Dissecans Patellae remains controversial. We present a family suffering from the condition in all members of one generation. Clinical data support the hypothesis that the aetiology of the disorder in this family is recurrent subluxation of the patella, the inherited predisposing factor being an abnormality of the mechanics of the knee. PMID- 1428307 TI - The long term outcome of open total and partial meniscectomy related to the quantity and site of the meniscus removed. AB - Two hundred patients were randomly selected for either a partial or a total meniscectomy for a meniscal tear during open operation. They were followed for a median of 7.8 years after operation. After partial meniscectomy, posterior horn tears had the worst outcome, but this was only apparent when more than two-thirds of the meniscus had been removed. The amount of meniscal tissue excised was inversely related to the function of the knee, except with bucket-handle tears treated by partial meniscectomy. Patients with bucket-handle, anterior and posterior horn tears had similar functional results after total meniscectomy. Preservation of the peripheral rim of the meniscus following partial meniscectomy produces the best functional results. PMID- 1428309 TI - Synovial haemangioma of the knee joint. AB - Synovial haemangioma of joints are rare, but usually affect the knee joints of children and adolescents. Recurrent swelling, usually due to haemarthrosis, and intermittent pain may be present for a long time before the diagnosis is made. In this case report the common features of the condition are described, with emphasis on the occurrence of atraumatic haemarthrosis in children. The value of arthroscopy in diagnosis is discussed. PMID- 1428310 TI - Intertrochanteric osteotomy for the treatment of chronic slipped capital femoral epiphysis. AB - Thirty six patients with a chronic slip of the capital femoral epiphysis and a femoral headneck angle of more than 30 degrees, as measured in a lateral radiograph, were treated by intertrochanteric osteotomy. The patients had an abnormal gait, an average age of 14.1 years and symptoms for an average of 14.5 months. The postoperative complications included two patients with avascular necrosis of the femoral head, four with coxa vara and two with loss of position requiring further operation. At an average of 7.5 years after operation 14 were good, 18 fair, and 4 poor on clinical assessment, with 13 good, 19 fair and 4 poor when judged by radiographs. Patients with complications had only fair or poor results. A postoperative head-neck angle of less than 10 degrees indicated a good result. PMID- 1428311 TI - The management of unreduced traumatic dislocation of the hip in developing countries. AB - Traumatic dislocation of the hip often remains untreated in developing countries. This paper reports the outcome of twenty nine patients with neglected dislocations (3 anterior and 26 posterior). We have outlined the indications for five different methods of treatment. An attempt has been made to explain the causes of poor results. PMID- 1428313 TI - Experimental kyphoscoliosis induced in rats by selective brain stem damage. AB - The relationship between damage to particular brain stem nuclei related to postural control and equilibrium and the occurrence of spinal deformity has been investigated. The model used was the Wistar albino rat and the brain stem structures damaged were the gracillis nucleus, the superior colliculus and the lateral vestibular nucleus. Out of 60 brain stem damaged animals, 44 had accurate lesions from which 11 (25%) showed kyphoscoliotic deformities. Rats with spinal deformity showed an imbalance of the paraspinal muscles when assessed by EMG; this was expressed by an increase of muscular activity on the convex side. This study indicates that postural dysfunction caused by brain stem damage may induce kyphoscoliosis in experimental animals and could be one of the underlying mechanisms in the production of human idiopathic scoliosis. PMID- 1428314 TI - Failed lumbar spinal surgery. AB - Failures and poor results of 160 patients after lumbar spinal surgery between 1980 and 1984 were analysed retrospectively. A self-rated questionnaire carried out 12 months after operation revealed 20 poor results; these occurred most commonly after multiple operations, decompression and fusion as compared to disc excision. The commonest cause was failure to recognise abnormal pain behaviour before operation. A more careful preoperative assessment should reduce the incidence of failure. PMID- 1428312 TI - The suppression of heterotopic ossification after total hip arthroplasty. AB - In a double-blind prospective randomised study we examined the effects of Diclofenac on heterotopic ossification after hip arthroplasty. Either the drug, or a placebo, was given by mouth to 158 patients in doses of 3 x 50 mg for 6 weeks. Diclofenac resulted in highly significant improvement (p less than 0.0001 versus controls) without severe side-effects. Heterotopic ossification decreased from 55% in the placebo to 15%. Significant degrees of heterotopic ossification did not occur with the drug. Movement of the hip was considerably increased after operation. We recommend Diclofenac prophylaxis against heterotopic ossification after hip operations in view of the serious clinical effects of this complication and its quoted incidence of 15% to 80%. PMID- 1428315 TI - [Clinical results of the treatment of chronic hematogenous osteomyelitis of the femur by operation. A series of 165 cases]. AB - Between 1968 and 1987 the authors treated 165 cases of chronic haematogenous osteomyelitis of the femur by operation. The procedure used combined decompression, sequestrectomy and saucerization in 161 cases, and sequestrectomy alone in 4. Chemotherapy was used in association for between 10 and 60 days. Eleven patients, thought to be healed, were lost to follow-up after 4 months. The remainder were reviewed for between 4 and 252 months, 124 for more than one year. After the first operation 105 lesions (64%) healed completely, while 60 (36%) relapsed. Of these, 48 were treated by further operation and 12 by drainage of the abscess. Nine patients relapsed twice and there were 3 or more relapses in a further 9. When last seen, 147 lesions were healed and 18 had a permanent sinus. Special features in relation to the femur are discussed, including destructive lesions of the knee and hip joints, the high incidence of stiffness of the knee even in the absence of radiographic evidence of destruction (48.5%), and the danger of injuries to the femoral vessels when using an approach through a medial sinus. The frequency of occurrence of lesions on both medial and posterior aspects of the femur has led the authors to recommend definitive surgical approaches, especially the true postero-lateral and antero-medial routes. Unsatisfactory results after operation may be due to the difficulty in performing sequestrectomy in deep and extensive lesions, problems in undertaking adequate saucerization and the lack of muscle to fill the residual cavity. PMID- 1428316 TI - Evaluation of radiological investigations in spinal tuberculosis. AB - Thirty-four cases of spinal tuberculosis were investigated by plain radiography, computerised tomography and myelography followed by computerised tomography. All the patients were operated on and the findings compared with the results of the investigations. PMID- 1428317 TI - Reconstruction of the pelvic ring after tumour resection. AB - Three different types of vascularised bone grafts have been used to reconstruct the pelvic ring after resection of tumours. Rapid bone healing is guaranteed and the period of rehabilitation is lessened compared with conventional methods. PMID- 1428318 TI - Intraoperative radioactive localization of small bone tumours. AB - A sodium-iodide scintillation probe and a portable scaler rate-metre were used to localize small bone tumours at operation, after the preoperative injection of technetium-99m methylene diphosphonate. This technique allows complete removal of the tumour nidus of an osteoid osteoma or the active part of other lesions without undue sacrifice of the surrounding bone. The method has been used for successful relief of pain in thirteen patients. PMID- 1428320 TI - Osteofibrous dysplasia of the tibia treated by bracing. AB - Osteofibrous dysplasia of the tibia in children will commonly recur after surgical resection. The use of a leg brace until puberty offers a useful method of conservative management. Seven female patients, age three months to nine years at the time of brace treatment, have been followed for 3.5 to 18 years, an average of nine years, with evidence of satisfactory healing of the lesions in all. Three of the cases had recurred after surgery, two with fibular grafts and one required leg lengthening. The use of a brace to control bowing of the tibia while awaiting spontaneous regression is advised until epiphyseal closure. PMID- 1428319 TI - Allogenic decalbone in the repair of benign cystic lesions of bone. AB - Forty-six cases of benign cystic lesions of bone were treated by curettage and compact filling using partially decalcified allogenic bone graft (Decalbone); of these, 35 were available for study. Decalbone was prepared by partial decalcification with 0.6 N hydrochloric acid (HCl) of human bones generally obtained from freshly amputated limbs. The commonest lesions of bone were giant cell tumours (14) and aneurysmal bone cysts (15), and the commonest bones involved were the femur (23) and the tibia (12). There was one failure and four recurrences. Five cases were infected but this did not interfere with healing of the primary lesion. Radiological incorporation of the graft was seen at about 3 months in unicameral bone cysts, at 4-6 months in aneurysmal bone cysts and at 6 9 months in giant cell tumours. There was no recurrence in any case of giant cell tumour, but three aneurysmal bone cysts recurred. There was no clinical immune reaction. PMID- 1428321 TI - Leiomyosarcoma of the great saphenous vein. AB - Primary malignant tumours of the great saphenous vein are extremely rare with only 15 cases reported in the English literature since 1919. We report a patient who survived 5.5 years after treatment with surgery and chemotherapy before dying from lung metastases. PMID- 1428322 TI - Arthrolysis in the relief of post-traumatic stiffness of the elbow. AB - A retrospective clinical study of 34 patients treated by arthrolysis for elbow stiffness is presented. These patients had sustained previous injury which was a simple fracture in 44%. The average age at operation was 31 years with a range from 6 to 57 years. Follow up for a minimum of one year, and an average of four years, showed an increase of motion from a preoperative average of 45 degrees to a postoperative average of 92 degrees with few complications and only three unsatisfactory results. This analysis has allowed conclusions concerning the technique and indications for operation. PMID- 1428323 TI - Simultaneous flexion of the thumb and index finger after a fracture of the first metacarpal bone. A case report. AB - We report a case in which simultaneous flexion of the thumb and index finger occurred after a fracture of the 1st metacarpal bone. This was demonstrated to be due to a fibrous adhesion around an anomalous slip between the tendons of flexor pollicis longus and flexor digitorum profundus indicis. PMID- 1428324 TI - Chondromyxoid fibroma of the scapula. A case report. PMID- 1428325 TI - [Walking in children after poliomyelitis]. AB - Between 1983 and 1990 the authors examined 630 children who had suffered from poliomyelitis, mostly between the age of one and three, at an average age of 9 years 3 months. Half were unable to walk because of residual paralysis. Operation was carried out on 252 children. Most underwent soft tissue release at the hips, knees or tendo Achilles. Triple arthrodesis was carried out on 24. Calipers, produced locally, were used, and trunk bracing was not employed. The average duration of treatment was 3 months, with gradual achievement of correction. Vascular complications occurred in one leg, there were 5 paralyses of the sciatic nerve and 4 fractures of the upper tibia. One hundred children who were not able to walk before operation were reviewed. Sixty five were walking and able to go to school. The best results were achieved before the age of 12. PMID- 1428326 TI - Bilateral ankylosis of the hips following heterotopic ossification of the ilio psoas in a child. AB - A case of bilateral ankylosis of the hip in a 3-year-old child due to heterotopic ossification of the iliopsoas following a long period of coma is presented. A review of the literature has failed to reveal a similar case with such extensive heterotopic ossification. The patient was treated successfully by surgical excision of the heterotopic bone which was extra-articular and extra-capsular and involved only the iliopsoas muscles. PMID- 1428327 TI - Pulmonary function in adolescents with idiopathic scoliosis. AB - Two groups of patients, with an average age of 15 years, have been studied to establish the improvement in pulmonary function after surgical correction in relation to the amount of correction achieved. The first group of 33 patients were treated surgically; an average Cobb angle of 72 degrees was reduced to 32.6 degrees. The second group of 30 patients with an average Cobb angle of 33 degrees were not operated on. Results of tests undertaken have shown that pulmonary function was improved by surgical correction, but the improvement does not match the degree of correction achieved. Statistical analysis of the two groups shows a difference in cardiopulmonary function to the advantage of those who were not operated on. This suggests that there is partial irreversibility of ventilation and perfusion in those who are treated surgically. PMID- 1428328 TI - Correction of the sagittal plane in idiopathic scoliosis using the Zielke procedure (VDS). AB - This paper reports a retrospective review of 91 patients with idiopathic thoracic scoliosis corrected by Zielke VDS instrumentation. The results were analysed to demonstrate the correction in all three planes. Satisfactory correction was obtained, and was particularly good in the sagittal and horizontal planes. There were no disadvantages from the thoracotomy. PMID- 1428329 TI - Operative treatment of unstable thoracolumbar fractures by the posterior approach with the use of Williams plates or Harrington rods. AB - Two similar groups of patients with unstable fractures and fracture dislocations of the thoracic or lumbar spine have been treated with the posterior application of Williams plates or Harrington distraction rods over a period of 10 years. The instrumentation was routinely removed from 13 to 19 months after insertion. The initial preoperative kyphotic angle was corrected by a mean of 4.5 and 6.9 degrees respectively. However, follow up after a minimum of four years has shown a loss of correction by a mean of 14.4 and 12.7 degrees to an angle of 21.9 degrees even in the Harrington rod cases. These results do not show the ability to maintain correction of deformity by either method with a dorsal approach. Reduction and stabilization of fractures of the spine should be directed to the anterior part of the vertebrae to overcome late deformity of the spine. PMID- 1428330 TI - Translaminar screw fixation of the lumbar spine. AB - Lower lumbar spinal fusion was carried out in 72 patients by a technique which involved screw fixation of the facet joints. Stability was achieved and mobilisation was allowed immediately. Radiographs after operation showed bony fusion in 94.5%. Pain was diminished and 76% of the patients would undergo the same treatment again. There were no neurological complications. The technique is useful and safe for the fusion of short segments of the lumbar spine. PMID- 1428331 TI - Halo-cast treatment of fractures and dislocations of the cervical spine. AB - Twenty-eight consecutive patients with dislocated, and often unstable, injuries of the cervical spine were treated by halo-cast stabilisation. One died and 27 were followed up. Twenty had no symptoms and 17 had full movement of the neck. There were only a very few minor complications. Seven patients had initial neurological impairment. They included the single death, but the remaining 6 regained useful muscle function. The halo-cast allows complete reduction in many types of fractures and dislocations, and good immobilisation is maintained. PMID- 1428332 TI - Transplantation of an island fascial flap with a vascular pedicle for arthoplasty of the hip. AB - Intra-articular transplantation of a vascularised island fascial flap has been used for arthroplasty of the hip in 18 patients with an average age of 22 years. They have been followed up for an average of 3 years; 14 were graded excellent and 4 good using the criteria of Charnley and Wu Zhikang. The procedure has a place in the treatment of hip disease in the younger patient. PMID- 1428333 TI - Listeria infection in an old hip implant. PMID- 1428334 TI - Listeria monocytogenes infection in prosthetic joints. AB - Listeria monocytogenes is increasingly recognised as a cause of prosthetic joint infection. These infections tend to be more insidious and indolent in contrast to similar infections with Staphylococcus aureus. They can occur in patients who are immunocompromised due to malignancy or other illness or in nonimmunocompromised elderly patients. Listeria infections should not be treated with cephalosporins and prolonged antimicrobial treatment is generally advised for prosthetic joint infections. We noted a high affinity of L. monocytogenes for foreign bodies. Three of twenty-seven cases 11%) of listeriosis under the period of investigation were associated with foreign bodies (hip prosthesis, knee prosthesis and arterial graft). PMID- 1428336 TI - Macrodactyly of the hands and feet. AB - Sixteen patients with macrodactyly have been reviewed; the hand was involved in 9 (one was bilateral) and the feet in 7. The condition was familial in 3. No qualitative difference was found between the static and progressive types. In the hand, the digital nerve was enlarged and lengthened whereas in the foot it looked normal. Microscopy showed infiltration of the nerve by fat and fibrous tissue in the hand and only slight perineural fibrosis in the foot. PMID- 1428335 TI - Rotator cuff tears in anterior dislocation of the shoulder. AB - We diagnosed 16 rotator cuff tears in 109 shoulders in 104 patients with a traumatic anterior dislocation. Twelve of these were followed up for an average of 32 months. A surgical repair of the cuff was carried out in eleven and the results were satisfactory in eight (73%) regardless of a Bankart lesion. The repair of a torn cuff seems to be sufficient to stabilise the shoulder in elderly patients, even when a Bankart lesion is present and is not repaired. PMID- 1428338 TI - Injuries in paragliding. AB - In a retrospective study, 376 paragliding accidents have been analysed. Leg injuries were most common, but a large number of spinal injuries also occurred. The causes were either misjudgement by the pilot or the influence of weather and terrain. Improvements in the instructor's knowledge and the pilot's training could have prevented most of the accidents. Analysis of the mechanisms of the crashes and the pattern of trauma help to produce an efficient approach to diagnosis and treatment. PMID- 1428337 TI - [Absorbable rods and screws: a new method of fixation for fractures of the olecranon]. AB - Between April 1986 and July 1990 fractures of the olecranon in 41 adult patients were treated by fixation with absorbable rods (20 patients) and screws (21 patients) of self-reinforced polyglycolide (SR-PGA), 3.2 mm in diameter and 20-70 mm in length. Patients were followed up for a mean time of 2 years 7 months (range 1 year to 4 years 6 months). After reduction of the fracture, channels were drilled from the proximal fragment through the cortex of the distal fragment and the fractures were fixed with absorbable rods or screws. By one year from follow-up maintenance of an anatomical reduction of the fracture was seen in 34 patients. Failure of fixation requiring a second operation occurred in 2 cases. In all cases functional recovery was at least satisfactory. Sinus formation as a sign of transient tissue reaction was observed in 3 cases, but did not influence the healing of the fractures or the functional recovery. The results in patients treated with rods or screws was similar. Absorbable screws combined with small rods and absorbable sutures allow treatment of +ore severe fractures of the olecranon than do rods alone. PMID- 1428339 TI - Prediction of late complications of femoral neck fractures by scintigraphy. AB - A prospective study was undertaken to determine the value of scintigraphy in predicting nonunion or necrosis of the femoral head following femoral neck fractures. Scintigraphy was carried out in 49 patients before operation and in 37 one week after operation; in 18 it was done before and after operation. The uptake of isotope was estimated visually as either normal or reduced compared to the opposite side. All the patients were followed up for at least 2 years. The results indicate that pre-operative bone scintigraphy is useful in elderly patients to predict nonunion and necrosis, and therefore is recommended to select those patients who will benefit from primary arthroplasty instead of fixation of the fracture. PMID- 1428340 TI - Fixation of fractures by twisted plates. A new concept of osteosynthesis. AB - A new twisted plate has been designed for biplane fixation of diaphyseal fractures of long bones. Comparative mechanical testing of the new twisted plate and conventional flat plates showed that the twisted plate was 40% stronger when a bending moment was applied and 132% stronger to a twisting moment. The overall improvement in strength was 90.5%. Clinical trials have been carried out and this paper describes the use of the new plate. PMID- 1428341 TI - The deltoid muscle: an electromyographical analysis of its activity in arm abduction in various body postures. AB - We have carried out an electromyographical examination of the activity of five different regions of the deltoid muscle during abduction/adduction in various body postures with different biomechanical actions of arm gravity. The results show that the deltoid action is highly differentiated in its different regions and is not restricted only to the generation of an abducting moment in the shoulder joint. There is obviously a biomechanical contribution, mainly by its spinal and clavicular regions, to the stabilization of the glenohumeral joint and to the control of the selected plane of abduction. PMID- 1428343 TI - A new method for measurement of femoral anteversion. A comparative study with other radiographic methods. AB - A new biplanar method of measuring femoral anteversion, which may be considered a modified Magilligan's method, is described. In addition to the true antero posterior radiograph, a true translateral radiograph is taken, instead of a transcervical lateral radiograph as in the Magilligan method. The acute angles (alpha and gamma) between the long axes of the shaft and neck of the femur on both the antero-lateral and lateral radiographs are measured. The angle (gamma') of anteversion is obtained by the trigonometric formula; tan gamma' = tan/tan alpha. The femoral anteversion in 20 adult dried femora and 40 femora in 20 children was measured by the Magilligan method, the authors' method and the conventional CT method. Compared with direct measurement in the dried femora, it was found that both the Magilligan and the authors' methods tended to overestimate and the CT method tended to underestimate (p < 0.05) the anteversion. In children's femora, a similar trend was observed among the three methods and the measurements by each method differed significantly from the other (p < 0.05). We feed that our method of biplanar measurement of femoral anteversion is more accurate, although probably marginally, than the conventional Magilligan method. It also has some relative advantages in clinical application in that positioning is easier, rotation is better controlled, and less time is consumed. PMID- 1428342 TI - The diagnostic significance of anti-type II collagen antibody assay in rheumatoid arthritis. AB - An improved enzyme-linked immunosorbent assay (ELISA) for the detection of anticollagen antibodies in human serum has been developed. With the use of this method, antibodies against native human Type II collagen were detected in 22.7% of sera from 480 patients with rheumatoid arthritis (RA). The antibodies were found to be collagen type specific, showing no reaction with human Type I and Type III collagens. The antibodies appeared in high incidence during the early phase of the disease, and RA patients with involvement of a single joint, mono articular arthritis, were often positive for anti-Type II collagen antibodies. In most of these patients, anti-Type II collagen antibodies preceded the appearance of rheumatoid factors. The antibodies were all negative in sera from patients with gout, osteoarthritis (OA) and non-arthritic diseases. Thus, anti-Type II collagen antibody assay may have diagnostic significance for RA patients, especially those in whom laboratory and clinical findings provide only minimal help in diagnosis. PMID- 1428344 TI - Patellar metastasis from a malignant melanoma. AB - We report a patient with a patellar metastasis from a malignant melanoma. Only 16 other cases have been previously described in detail in the literature. A lytic lesion in the patella is most often caused by a benign tumour, but a primary or secondary malignant tumour has to be excluded. PMID- 1428345 TI - Comparison of magnetic resonance imaging and computed tomography in the local assessment of osteosarcoma. AB - We have compared the value of magnetic resonance imaging (MRI) with computed tomography (CT) in assessing the extent and the localization of osteosarcomas. Twenty patients were examined by both systems, and the results related to the clinical and histological findings. While both investigations are valuable, MRI may be more useful for defining the local extent of an osteosarcoma. PMID- 1428346 TI - One session surgery on the lower limb in children with cerebral palsy. A five year follow-up. AB - Twenty three children with cerebral palsy, who were operated on upon before 1984, have been re-assessed. All the lower limb deformities were corrected in one surgical session. Review after five years included foot-switch measurements and assessment of video recordings. There were no recurrences, and gait ability showed normal growth-related development. PMID- 1428347 TI - Morton's neuroma. AB - During the past 10 years we have operated on 75 feet for Morton's neuroma with a minimal follow up of nine months. Associated anomalies were found in 80%. Pathological studies demonstrated that the lesion was irritative in nature. The clinical results were satisfactory in 94%. PMID- 1428348 TI - Humoral immune responses in osteomyelitis. AB - Fifty-three patients with osteomyelitis were grouped according to the duration of the disease at presentation, the bone and the part involved, the aetiology, activity, severity and stage of disease. Sera from these patients was estimated for IgA, IgM and IgG levels and in 23 matched controls. The results were compared with the normal range, and correlative studies were carried out between serum immunoglobulin levels and the different clinical parameters. Serum levels of the 3 immunoglobulins were found, in general, to fail to rise above the normal in the presence of infection. Furthermore, the levels did not show significant variation with the clinical parameters. These findings suggest that there is an intrinsically subdued immune response to osteomyelitis in most of the patients, partly confirming the suspicion of an immunodeficient state. PMID- 1428349 TI - Septic arthritis in HIV positive haemophiliacs. Four cases and a literature review. AB - Septic arthritis is rare in haemophiliacs. Four new cases who were also HIV positive are reported. In three, the knee was involved, and in the fourth the elbow. The organism was streptococcus pneumoniae and staphylococcus aureus in one patient each, and salmonella in two. Although all the patients were human immunodeficiency virus (HIV) positive at the time of diagnosis, only two patients developed autoimmune deficiency syndrome (AIDS) after their septic arthritis. These two died later due to AIDS complications. Treatment was conservative in all cases with antibiotic therapy and prompt rehabilitation. The results were fair in two and good in two. Therefore nonoperative management is advocated before surgical drainage is considered. It seems likely that a positive HIV status is related to the appearance of septic arthritis in haemophiliacs. PMID- 1428351 TI - "Existential" therapists and their group therapy practices. AB - Existential philosophical thought insists that human behavior is indeterminate and subject only to the individual's will. It is, therefore, skeptical of all dynamic psychologies based as they are on Freudian determinism. Group therapists imbued with this philosophy stop short of its extreme. Their existential position, however, does greatly modify treatment, and yet they preserve both the form and goals of therapy. They place properly selected and prepared patients in a group where their individuality and authenticity are highly valued. Finding most technical procedures irrelevant, the therapists themselves, that is, their evolving personalities are central. The key to patient change is the spontaneous meeting of members and the therapist which the therapist orchestrates. Instead of the usual interpretation, members are encouraged to confront the paradoxes in their lives, their humanness, and especially their finitude. Patients are to be brought up to the threshold of their self-knowledge so they can choose. Choice, therefore, along with action coupled with responsibility are frequent themes. Unless the individual is incompetent, decisions made for him or her by the therapist or by group consensus are thought to be nontherapeutic. PMID- 1428350 TI - Orthopaedic complications in sickle cell disease. A comparative study from two regions in Saudi Arabia. AB - The haematological and orthopaedic complications of patients with sickle cell disease from two different regions of Arabia are presented. Nineteen patients from the South-western region were matched for age and sex with an equal number from the Eastern region. The mean sickle cell haemoglobin was 75.95% in those from the South-west and 77.5% in those from the East. The haemoglobin concentration was marginally lower in the Eastern region patients at 9.19 g/% compared with 9.51 g/%. Bone and joint infections occurred in 17% of Eastern region patients and in 15% in those from the South-western region. There was no significant difference between the haematological parameters and the orthopaedic complications in the two regions. We conclude that these complications are severe in the Eastern region and the disease is not benign as previously thought. Aggressive treatment of orthopaedic complications is indicated in sickle cell disease in the Eastern region. PMID- 1428352 TI - Group-analytic psychotherapy. AB - Group analysis is a flexible and effective method of providing group psychotherapy, thereby promoting maturation and symptom relief. Its metapsychology remains incompletely worked out but provides potentially exciting interfaces with biological and physical sciences, through Foulkes's (1973) seminal concept of the group matrix. PMID- 1428353 TI - Psychodrama: group psychotherapy through role playing. AB - The theory and the therapeutic procedure of classical psychodrama are described along with brief illustrations. Classical psychodrama and sociodrama stemmed from role theory, enactments, "tele," the reciprocity of choices, and the theory of spontaneity-robopathy and creativity. The discussion focuses on key concepts such as the therapeutic team, the structure of the session, transference and reality, countertransference, the here-and-now and the encounter, the group-as-a-whole, resistance and difficult clients, and affect and cognition. Also described are the neoclassical approaches of psychodrama, action methods, and clinical role playing, and the significance of the concept of behavioral simulation in group psychotherapy. PMID- 1428355 TI - Commentary: therapy for individuals or remediation for groups? A fateful ethical choice. PMID- 1428354 TI - Feminism and group psychotherapy: an ethical responsibility. AB - In response to Martin Lakin's (1991) IJGP article, "Some Ethical Issues in Feminist-Oriented Therapy Groups for Women," this article examines recent developments in feminist theory and proposes that a feminist perspective is both ethical and can make significant contributions to the practice of group psychotherapy. The overview of feminist theory focuses on (1) the importance of the social context, (2) contributions and challenges to psychoanalytic and developmental theory, (3) attention to power relations, (4) the connection between the personal and political, and (5) recognition and integration of diversity and difference. Clinical examples illustrate ways in which male and female group therapists can take a feminist perspective and become "ethical advocates." PMID- 1428356 TI - Commentary: the group in psychodynamic group psychotherapy. PMID- 1428357 TI - Modulation of IL-2, IFN-gamma, TNF-alpha and IL-4 production in mice of different ages by thymopentin. AB - The effect of an immunomodulator drug thymopentin (TP5) on the production of various cytokines (IFN-gamma, IL-2, IL-4, TNF-alpha) in mice of different ages has been studied. TP5 enhanced IL-2, TNF-alpha and IFN-gamma production but reduced the IL-4 secretion by splenocytes from aged mice (greater than 120 week old) in vitro. However, it had no effect on the IL-2, IFN-gamma, TNF-alpha or IL 4 production by splenocytes from young and adult mice. TP5 injected subcutaneously was able to induce high levels of IL-2 production by splenocytes from all groups of mice. The TP5 effect on TNF-alpha and IFN-gamma was similar, even though it was significant only in old mice. Furthermore, TP5 was able to significantly reduce IL-4 production in old mice, which normally produced high levels of this cytokine after mitogen stimulation. Since it has been observed in the mouse that the Th1 cells secrete IFN-gamma and IL-2, whereas the Th2 cells preferentially produce IL-3, IL-4 and IL-5, these results indicate that the immunopotentiatory activity of TP5 is due to the preferential up-regulation of Th1 cells. PMID- 1428358 TI - Low dose streptozotocin-induced diabetes in mice: reduced IL-2 production and modulation of streptozotocin-induced hyperglycemia by IL-2. AB - The possible role of interleukin 2(IL-2) in the pathogenesis of multiple low dose streptozotocin (Sz)-induced diabetes in mice was analysed. Spleen cells from diabetic male C57Bl/6 mice showed diminished mitogen-induced IL-2 production as determined by bioassay using the IL-2-dependent T-cell line CTLL-2. In parallel the proliferative response was reduced. Systemic daily administration of human recombinant IL-2 for 3 weeks had dose-dependent effects on the development of hyperglycemia in Sz-treated (5 x 40 mg) mice: while IL-2 at doses of 1 x 2, 1 x 10, 2 x 10 micrograms/kg body weight caused partial suppression of hyperglycemia, higher doses (2 x 20, 2 x 40 micrograms/kg) had an enhancing effect. Treatment with the lowest dose (1 x 1 micrograms/kg) or with a control preparation from bacteria (2 x 10 micrograms/kg) did not significantly alter the course of diabetes. Effects of IL-2 were similar when treatment was started concomitantly with or only after streptozotocin injections. This observation argues against the direct interaction between IL-2 and streptozotocin but suggests modulation of immune reactivity by IL-2. Our findings of decreased mitogen-stimulated IL-2 production by splenic lymphocytes, and the disease-modulating effect of IL-2 in the low-dose streptozotocin diabetes extend our previous observations in spontaneously diabetic BB rats and further support the notion of an involvement of IL-2 in the control of autoimmune diseases. PMID- 1428359 TI - Differential sensitivity of in vivo TNF and IL-6 production to modulation by anti inflammatory drugs in mice. AB - The effect of dexamethasone and two non-steroidal anti-inflammatory agents ibuprofen and indomethacin on the production of serum interleukin 6(IL-6) and tumor necrosis factor (TNF) levels in mice treated with endotoxin (2.5 micrograms/mouse, i.p.) was investigated. Pretreatment of mice with dexamethasone (0.3-30.0 mg/kg, i.p., 30 min before endotoxin) completely blocked TNF production but did not affect that of IL-6. Conversely, pretreatment with indomethacin (5 mg/kg, i.p.) or ibuprofen (30 mg/kg, i.p.) potentiated the production of both IL 6 (+ 80% with INDO; + 100% with IBU) and TNF (+ 500% with INDO; + 50% with IBU). In the case of IL-6, the two anti-inflammatory drugs were able per se to induce significant levels of this cytokine even in the absence of LPS. These data indicate that IL-6 and TNF production are differently susceptible to glucocorticoids, and that prostaglandins can physiologically provide a negative feedback regulation of IL-6 and TNF synthesis. PMID- 1428360 TI - The in vitro effects of mercury on peritoneal leukocytes (PMN and macrophages) from inbred brown Norway and Lewis rats. AB - The present paper demonstrates that HgCl2 can affect rat peritoneal polymorphonuclear leukocyte (PMN) and macrophage (M phi) functions in vitro. In addition, we have noticed that these effects of mercury vary according to the rat strain: for example, HgCl2 stimulates H2O2 release from Lewis (LEW) but not Brown Norway (BN) PMN. Similarly, LEW M phi produce high levels of H2O2 when exposed to HgCl2 in vitro, whereas BN M phi do not. Finally, mercury inhibits erythrophagocytosis of both LEW and BN "resident" peritoneal M phi. Preliminary experiments using M phi from other rat strains have also shown that MAXX M phi are stimulated by HgCl2 to release H2O2 in vitro, whereas Yoshida M phi are inhibited. Differences in lymphocyte responses (e.g. delayed-type hypersensitivity reactions and mitogen stimulation) between rats of various strains are well known. To these examples one may now add variations in PMN and M phi responses to mercury and possibly other metals. Our results suggest that caution should be exercised in interpreting the outcome of immunotoxicity studies in experimental animals. In particular, outbred rats may not provide appropriate models, that might be better obtained by comparative investigations of rats from various inbred strains. PMID- 1428361 TI - In vitro activation of murine peritoneal exudate cells (PEC) and peritoneal macrophages by ST 789. AB - ST 789 is a new synthetic compound characterized by an amino acidic group joined to the N9 position of the hypoxanthine ring, which has been shown recently to have immunomodulating properties and minimal toxicity. The drug has been reported to protect immunosuppressed mice from microbial infections and tumour growth, and to restore the mitogen-induced proliferation of splenocytes from immunosuppressed young mice. In this study, we show that in vitro addition of ST 789 is able to markedly augment the sheep red blood cells (SRBC) phagocytosis by PEC, and to potentiate the cytotoxic activity of peritoneal exudate (PE) macrophages (M phi) vs the L-M tumour cell line. We also found that ST 789 enhanced the rIFN-gamma induced NO2- release from cultured PE M phi. Similarly, in vitro addition of ST 789 to the latter cultures significantly increased the production of interleukin 1 (IL-1) and tumour necrosis factor (TNF) induced by lipopolysaccharide (LPS). These studies demonstrate that ST 789 is a potent phagocyte activator for the induction of cytokine release, phagocytosis and cytotoxic activity against tumour cells in vitro. PMID- 1428362 TI - Antiviral activity of individual versus combined treatments with interferon alpha, beta and gamma on early infection with HTLV-I in vitro. AB - We have shown previously that infection of mononuclear cells derived from neonatal cord (CBMC) or adult peripheral (PBMC) blood with HTLV-1 can be controlled in vitro by treatment with interferon (IFN) alpha, beta or gamma. The activity of IFNs was mainly related to the induction of an active antiviral competence in host's immune effector cells. The antiviral activity of IFN-boosted CBMC could be ascribed both to a positive regulation of cell-mediated immunity and to inhibition of viral infection. Data described herein provide further information on the mechanisms of the antiviral activity of IFNs and compare the activity of each type of IFN with the association of alpha + beta, alpha + gamma and beta + gamma IFNs, at a concentration of 100 or 1000 IU/ml. When added at the onset of the co-culture of CBMC with lethally irradiated, virus-donor MT-2 cells, IFNs could protect host CBMC by inhibiting HTLV-1 infection in terms of reduced proviral integration and a lower percentage of virus-positive cells, until 4 weeks of culture. Infection of CBMC was inhibited at a comparable extent by either individual or combined IFN treatments. However, a clearcut inhibition of HTLV-I transcription was found only when alpha 100 + beta 1000 IU/ml and especially alpha 1000 + gamma 100 IU/ml combined treatments were tested. When the chronically infected, virus-producing MT-2 cells were treated with IFNs, a remarkable inhibition of HTLV-I transcription was found only after multiple treatments. However, MT-2 cells became resistant to the antiviral activity of IFN gamma, but not to that of IFN alpha or beta. These data provide further information on the control of HTLV-I replication mediated by IFNs at different steps of the viral life cycle, being therefore relevant to the clinical use of combined IFNs in the treatment of acute infection. Moreover, IFNs could be used to prevent the establishment of a persistent infection, which is a prerequisite for developing adult T-cell leukemia (ATL) and/or virus-associated myelopathy. PMID- 1428364 TI - Effects of K-76COOH (MX-1) on immune response: induction of suppressor T-cells by MX-1. AB - K-76COOH (MX-1), isolated from the cultured supernatant of a species of fungi imperfecti, Stachybotrys complement nov. sp. K-76, is an inhibitor of the complement component, C5. The effects of MX-1 on various immune responses were investigated. MX-1 enhanced the response of spleen cells to PHA and LPS: MX-1 at 0.01-250 micrograms/ml for PHA and at 10-250 micrograms/ml for LPS. In contrast, it inhibited the response to Con A: MX-1 at 0.01-500 micrograms/ml for spleen cells and at 100-500 micrograms/ml for thymocytes. MX-1 and IL-1 synergistically acted to enhance the Con A response of spleen and thymus cells from which accessory cells and Ia-positive cells had been removed by passing through Sephadex G-10 columns and treating with anti-Ia monoclonal antibody plus complement. T-cells pretreated with MX-1, IL-1 and Con A for 3 days suppressed not only the response of B-cells to LPS but also the production of anti-SRBC antibodies. In addition, MX-1 was found to increase CD8+ T-cells. These results suggest that MX-1 acts on T-cells to induce suppressor T-cells. PMID- 1428365 TI - Effects of subcutaneous versus intravenous administration of cyclosporin A on rat thymic histology and pharmacokinetics. AB - Cyclosporin A (CsA) was administered to rats by repeated subcutaneous (s.c.) or intravenous (i.v.) injections for 14 days. Changes in thymic histology were independent of the route of administration. Blood concentration--time profiles of CsA were similar at dose levels of i.v. 7.5 and s.c. 15 mg/kg/day, respectively. So, provided that the dose is reduced, i.v. injection can serve as an adequate alternative to s.c. injection, thereby preventing unwanted painful side-effects associated with the latter route of administration. PMID- 1428363 TI - Spermine dialdehyde, a novel ex vivo purging agent for both allogenic and autologous bone marrow transplantations. AB - The use of ex vivo purging agents has shown to be beneficial for both allogeneic and autologous bone marrow transplantations. We have shown previously that spermine dialdehyde (SDA), an oxidized product of spermine, when used in phosphate-buffered saline (PBS) preferentially inhibits T-cell proliferation while sparing myeloid cells. Lethally irradiated mice were rescued by reconstitution with SDA-treated allogeneic marrow and showed no sign of graft-vs host disease (GVHD). In this paper, we show by HPLC analysis that SDA degraded rapidly in PBS but remained intact in saline. Administered in saline, SDA was more inhibitory on leukemic cell lines than normal myeloid or T-cells. Lethally irradiated mice receiving a syngeneic bone marrow leukemic cell mixture treated ex vivo with SDA in saline did not manifest leukemia. Thus, the preferential inhibitory effect of SDA and its degraded products in different buffers suggest that SDA could act as a novel purging agent for both allogeneic and autologous bone marrow transplantations. PMID- 1428366 TI - Differential effect of dipyridamole upon thymidine incorporation and expression of surface activation antigens by in vitro stimulated lymphocytes. AB - Dipyridamole inhibits, by 50% at 10(-6) M and 100% at 10(-5) M, the incorporation of tritiated thymidine by lymphocytes stimulated with 1 microgram/ml phytohaemagglutinin A for 72 h. At the latter concentration, a clinically relevant one, dipyridamole fails to inhibit lymphocyte proliferation and expression of the cell surface stimulation markers, CD25 and HLA-DR, or differential regulation of the CD45 -RA and -RO isoforms, as determined by single laser two-colour flow-cytometry. No significant immunodepressant effect of dipyridamole can be demonstrated in vitro. PMID- 1428367 TI - Cocaine-induced suppression of interferon-gamma secretion in leukocytes from young and old C57BL/6 mice. AB - The effects of cocaine (0.1-100 micrograms/ml) were studied on interferon-gamma (IFN) secretion in Con A-stimulated splenocytes from young (4 months) and old (18 months) C57BL/6 mice. IFN secretion was significantly suppressed by cocaine in a concentration-dependent manner. Suppression was observed in splenocytes from both young and old mice. Splenocytes from young mice released higher amounts of IFN (23.40 +/- 1.47 ng/ml) than those from old mice (6.10 +/- 0.35 ng/ml) after 24 h in culture. The concentration of Con A used to stimulate IFN secretion significantly affected the suppressive effect of cocaine. Pretreatment of splenocytes with cocaine followed by culture in the absence of cocaine did not affect IFN secretion in old mice, while splenocytes from young mice showed a sustained depression in IFN release. This suggests that cocaine suppresses IFN release in vitro and the susceptibility to this inhibitory effect may be age related. PMID- 1428368 TI - Effect of apocynin on the induction of ulcerative lesions in rat skin injected with tubercle bacteria. AB - Apocynin is an effective and selective inhibitor of the neutrophil oxidative burst in vitro. Other neutrophil functions, tested in vitro, such as chemotaxis, exocytosis, phagocytosis and intracellular killing of bacteria are unaffected by apocynin. These properties make apocynin a potential anti-inflammatory agent in vivo. This was tested in WAG/Rij rats, injected intracutaneously with tubercle bacteria in oil (complete Freund's adjuvant). We show here that continuous administration of apocynin via the drinking water prevents the formation of ulcerative lesions in the inflamed skin. No effects on humoral and cellular immunity were observed after treatment with apocynin (between 1 and 100 micrograms/ml drinking water) measuring serum antibodies and delayed-type hypersensitivity, respectively. PMID- 1428369 TI - Immunosuppression of triptolide and its effect on skin allograft survival. AB - In this study the immunosuppressive properties of triptolide were evaluated. Triptolide was found to inhibit skin allograft rejection in a dose-dependent manner. This inhibitory effect was time dependent. Triptolide at 0.1 mg/kg/day significantly prolonged the graft survival when triptolide was given for 9 days after transplantation, but not before transplantation. In vitro studies showed that triptolide markedly suppressed cytotoxic T-lymphocyte (CTL) induction and mixed lymphocyte reaction (MLR) at concentrations ranging from 0.08 to 10 ng/ml. The inhibition on MLR was also significant when triptolide was added to the cultures at 36 h after initial incubation. Furthermore, exogenous IL-2 did not reverse this inhibitory effect of triptolide. Our results suggest that triptolide inhibits lymphocyte activation at a relatively late stage, and its effect on immune response is not exerted through altering IL-2 production. PMID- 1428370 TI - Stimulation of microbicidal host defence mechanisms against aerosol influenza virus infection by lentinan. AB - The ability of polysaccharide immunomodulator lentinan to stimulate non-specific resistance against respiratory viral infections was investigated. Significant protection was conferred by lentinan administered intranasally before lethal influenza virus infection and could be corroborated by a reduction of the lung virus titres. Since the lung is the target organ of influenza virus infection, lentinan was also administered by the intravenous route. Lentinan conferred complete protection against a LD75 challenge dose of virulent influenza virus and significantly prolonged the survival time after a LD100 challenge. The effect on respiratory burst of broncho-alveolar macrophages was investigated by luminol dependent chemiluminescence (CL) in response to stimulation by zymosan. Enhanced CL activity was present at an early stage in groups receiving lentinan. Significant nitric oxide activity could also be stimulated by culturing broncho alveolar macrophages in the presence of lentinan. TNF activity could not be detected in lung lavage but measurable IL-6 was produced already after 6 h in animals administered lentinan alone and in lentinan-pretreated influenza virus infected mice. Influenza virus alone did not induce measurable IL-6 at 6 h but high activity was present at later time periods. PMID- 1428371 TI - Immunopharmacological properties of azepino [2, 1-b] quinazolin-12(6H)-one-7, 8, 9, 10-tetrahydro (RLX). AB - The effect of azepino [2,1-b]quinazolin-12(6H)-one-7, 8, 9, 10-tetrahydro (RLX) was studied on cell-mediated and humoral components of the immune system. In single (50, 100 and 200 mg/kg) and multiple (6.25, 12.50, 25 and 50 m/kg) oral dose schedules RLX significantly reduced the early (4 h) and delayed (24 and 48 h) hypersensitivity reactions to SRBC in mice. Daily oral administration of RLX (25, 50 and 100 mg/kg) produced a dose-related reduction in developing adjuvant arthritis in rats. In carrageenan-induced pleurisy in rats RLX (25, 50 and 100 mg/kg p.o.) caused a marked reduction in the volume of pleural exudate (25.26 59.64%) and infiltration of leucocytes (28.75-50.29%) into the pleural cavity. RLX produced marked inhibition of humoral antibody synthesis both in mice and rats and that of complement fixing antibody in mice. It was not cytotoxic and showed no appreciable effect on the responsiveness of splenocytes to mitogens. The observed effect of RLX on cell-mediated and humoral immune responses does not appear to be the result of general toxicity. PMID- 1428372 TI - Human recombinant interleukin-1 receptor antagonist (hrIL-1ra) enhances the stimulatory effect of interleukin-2 on natural killer cell activity against MOLT 4 target cells. AB - Interleukin-1 (IL-1) is considered an enhancer of host defence against malignancies. Patients with different diseases, including cancer patients with large tumour burdens, have demonstrated a reduced production of IL-1 from circulating leukocytes, in vitro. There are many naturally occurring substances which inhibit IL-1 activity aspecifically. Recently an interleukin-1 receptor antagonist (IL-1ra) has been discovered, which is secreted by human macrophages and is structurally similar to IL-1 beta (26% homology). The pretreatment of human peripheral blood mononuclear cells (PBMC) with hrIL-1ra (0.25-250 ng/ml) inhibits IL-1 alpha or IL-1 beta and enhances, in a dose-dependent manner, the stimulatory effect of IL-2 on their natural killer (NK) activity against a lymphoid cell line MOLT-4. The enhancing effect of IL-1ra on IL-2 activity was similar to that provoked by IL-1 beta. However, when IL-1ra was used alone without IL-2, no stimulatory effect was found compared with the control. In our data we show that a member of the IL-1 family, IL-1ra, has a significant effect on IL-2-stimulated NK activity against the MOLT-4 cell line. These studies provide new evidence of the biological potential of IL-1ra since this new protein enhances IL-2 activity on NK cells. PMID- 1428373 TI - Hydrolysis and association of leucine enkephalin to lymphomic and erythroleukaemic cell lines--III. Soluble enzymes. AB - The possible existence of soluble proteolytic enzymes released by cells of lymphomic (U937 and 1301) and erythroleukaemic (K562) lines was studied measuring the hydrolysis of 3H-leucine enkephalin in the presence of cell-free supernatants. Results obtained indicate that in the presence of these supernatants leu-enkephalin rapidly disappears and that enkephalin disappearance is paralleled by the formation of peptides that can be interpreted as its hydrolysis fragments. Chromatographic analyses of cell supernatants indicate the presence of three groups of proteins active in leu-enkephalin degradation: aminopeptidases, dipeptidylaminopeptidases and dipeptidylcarboxypeptidases. In all three lines, soluble enzymes are represented by a sizeable number (from 13 to 25) of distinct activities. The number of enzymes identified and their considerable total activity suggest a possible role in the regulatory degradation of informational peptides, as proposed by several groups for the membrane-bound proteolytic enzymes of immunocompetent cells. PMID- 1428374 TI - The distribution of anaerobic energy in 1000 and 4000 metre cycling bouts. AB - In sprinting events of short duration, performance depends not only on the mean external power output and the frictional losses but also on the distribution of energy over the race. To investigate the optimal distribution of anaerobic energy during cycling the 1000 m time trial and the 4000 m pursuit, we simulated a power equation which contains expressions for the production of aerobic and anaerobic power, for frictional losses and for the rate of change of kinetic energy. Parameters for air- and rolling resistance were derived from the literature and the equations for aerobic and anaerobic power production were based on supra maximal bicycle ergometer tests. Simulated lap and final times were compared to those realized by the best four athletes during the 1990 World Championships. The mean final times of these athletes of 64.1 s and 272.6 s for the 1000 m and 4000 m respectively were closely approximated by the simulated times of 63.7 s and 281.3 s. The simulations show that performance in the 1000 m race depends to a great extent on a large power output at the onset of the race. Moreover, it is demonstrated that this distance should be cycled in an all out fashion and not with a uniform velocity after the start despite the higher air frictional losses. For the 4000 m pursuit it appears to be more effective to perform a short but powerful start and then continue the race with a constant or only slightly decreasing power output. PMID- 1428375 TI - Acute exercise and immune function. Relationship between lymphocyte activity and changes in subset counts. AB - Twenty-one young male subjects exercised on a cycle ergometer for 60 min at 60% of VO2max. Blood samples collected every 30 min throughout exercise and continuing to 120 min recovery served for the immunological tests. Exercise induced biphasic changes in the various leucocyte subsets. There was a granulocytosis, lymphocytosis and monocytosis during exercise, and a further granulocytosis and a slight monocytosis, but a lymphocytopenia during recovery. All lymphocyte subsets (CD3+, CD19+, CD4+, CD8+, and CD16+ cells) increased in number during exercise, were decreased 30 min after exercise, and had not returned to baseline levels by 120 min of recovery. The apparent lymphocyte responsiveness to the mitogens phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) declined significantly during exercise, returning to normal by 120 min of recovery. The natural killer (NK) activity rose markedly during exercise, but decreased to almost half the pre-exercise level at 30 and 60 min of recovery, returning to baseline levels after 120 min of recovery. Functional capability correlated well with the percentage of each major responder subset in the assay, suggesting that the in vitro lymphocyte PHA- and PWM-responsiveness and the NK activity did not change significantly on a per cell basis. The analysis of lymphocyte marker antigen density revealed that the CD3+, CD4+, CD8+ and CD19+ lymphocytes mobilized into the circulation during exercise did not express the respective CD3, CD4, CD8 and CD19 molecules as strongly as did the subsets circulating at rest, whereas the expression of the CD16 antigen on CD16+ lymphocytes remained unchanged. PMID- 1428376 TI - A comparative study of blood lactate analytic methods. AB - Three different blood lactate analytic methods were tested for precision, accuracy, linearity, and intermethod comparison: a photoenzymatic assay (PHE), and three electroenzymatic (EE) semiautomatic assays (EE1, EE2, EE3). Reference standards and duplicate capillary blood samples from the earlobe were used. Precision and accuracy of the three techniques, when measuring L-lactate standards, were good in the whole range of measurement (mean variation coefficient, VC = 1.78-3.38%; mean difference = 1.81-3.38%). Correlation between the three methods was high (r = 0.913-0.946), but all three electroenzymatic techniques systematically measured lower values as compared to the PHE tests. The differences ranged from 0.1-1.2 (5 mmol.l-1 PHE level), to 3.4-5.7 (20 mmol.l-1 PHE level). These differences were drastically reduced when a hemolyser and a glycolytic inhibitor were added to the sample prior to the assay. The measurements obtained in capillary blood by the three techniques are not equivalent. The differences are partially attributed to the fact that the PHE technique measures total blood lactate, while the EE methods only measure plasmatic-extraerythrocytic lactate. Some regression equations are presented that may be used to convert values measured by the PHE technique, to EE values and vice versa. PMID- 1428377 TI - Day to day variation in time trial cycling performance. AB - In an attempt to assess the reproducibility of laboratory cycling performance, eight well-trained (VO2max = 4.6 +/- 0.2 l.min-1) male cyclists completed 12 trials involving 4 successive performance rides at each of three total work outputs (approximately 1600, 200, and 14 kilojoules, respectively). These trials, designated as long, medium, and short trials (LT, MT, ST), represented exercise bouts of 105.12 +/- 0.41, 12.03 +/- 0.17 and 0.55 +/- 0.11 minutes, respectively. The trials, conducted on a computerized cycle ergometer in an isokinetic mode, were separated by a minimum of 72 hrs. All trials for each subject were completed at the same time of day. In all trials, subjects were allowed to select the pace in order to complete the ride in the shortest possible time. The mean coefficient of variation (CV) for performance time in each trial was: LT = +/- 1.01%, MT = +/ 0.95%, and ST = +/- 2.43%, respectively. The CV for performance time in ST was significantly greater than the CV in either LT or MT. In LT, performance time was significantly faster, and the mean % VO2max was significantly higher in trial 4 versus trials 1-3. There was no order effect in the MT or ST rides. The CV for mean VO2 (l.min-1), mean % VO2max, and RER during the LT rides were +/- 3.02%, +/ 3.64%, and +/- 3.53%, respectively. These data suggest that trained cyclists have the ability to reproduce endurance performance with a CV of approximately 1.0% in a time-trial protocol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428378 TI - Relationship between post-exercise plasma CK elevation and muscle mass involved in the exercise. AB - The purpose of this study was to investigate whether a larger post-exercise increase in plasma creatine kinase (CK) activity would be produced when a larger amount of muscle is damaged by eccentric exercise. Twenty-two non-weight trained females were placed into two groups; Group A (n = 12) and Group B (n = 10). Both groups performed 24 maximal eccentric actions of the forearm flexors on each bout. The right and left arm were exercised on the same day for Group A (24 eccentric actions per arm, a total of 48 actions). In contrast, Group B performed 24 actions with either the right or the left arm on the first bout and performed 24 eccentric actions with the opposite arm on the second bout 3-5 weeks later. Blood samples were taken before and for 5 days after each exercise and plasma CK activity was determined. Forearm flexion isometric force (ISO), range of motion evaluated by relaxed elbow joint angle (RANG) and flexed elbow joint angle (FANG), and perceived muscle soreness (SOR) were also examined to indirectly assess muscle damage. All of the muscle damage indicators changed significantly over time (p < 0.01) for both groups, but changes were not significantly different between arms or between groups. Because it seemed that both arms were equally "damaged" for each group, it was expected that Group A (two arms were exercised on the same day) should show an approximate two-fold increase in plasma CK compared to Group B when one arm was exercised on each bout.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428379 TI - Effects of voluntary exercise on bone growth and calcium metabolism in spontaneously hypertensive rats. AB - The effects of voluntary exercise on bone length and calcium metabolism were investigated in spontaneously hypertensive rats (SHR) and Wistar rats. They were classified into voluntary exercise or sedentary group. Systolic blood pressure (SBP), bone length, urinary calcium excretion, plasma calcium and parathyroid hormone levels (PTH) were measured for analysis. SBP of the trained SHR (T-SHR) was significantly lower than that of the nontrained SHR (NT-SHR) at 10 and 11 weeks of age, but the trained Wistar rats (T-WR) and the nontrained Wistar rats (NT-WR) had similar SBP throughout the experimental period. The T-SHR had significantly longer bones in the extremities and the trunk than the NT-SHR, whereas the T-WR had similar or shorter bones than the NT-WR. The PTH level at 12 weeks of age was significantly lower in the T-SHR than in the NT-SHR. The urinary calcium excretion of the T-SHR was greater than that of the NT-SHR, but the food intake (calcium intake) of the T-SHR was also greater. The urinary calcium excretion and food intake of the T-WR and NT-WR were similar. No noticeable differences were observed in the plasma calcium level between the T-SHR and NT SHR, the T-WR and NT-WR. From these results it is suggested that the abnormal calcium metabolism in the SHR is improved in some degree by voluntary exercise. PMID- 1428380 TI - L-tryptophan supplementation does not improve running performance. AB - In 1988 Segura and Ventura (14) reported that 1.2 g of L-Tryptophan (L-TRY) supplementation increased total exercise time by 49.4% when the subjects were running at 80% of maximal oxygen uptake (VO2max). In human performance research, acute improvements of that category are rather uncommon. Both for this reason and because ingestion of purified L-TRY may have adverse effects, it seemed pertinent to repeat the investigation of Segura and Ventura. Forty-nine well-trained male runners, aged 18-44, with an average maximal aerobic power of 66 (57-78) ml.kg 1.min-1, participated in a randomized double blind placebo (P) study. Each subject underwent four trials on the treadmill. The first two served as learning experience, including measurement of VO2max and anaerobic threshold. During the last two trials the subjects ran until exhaustion at a speed corresponding to 100% of their VO2max-first an initial trial and then after receiving a total of 1.2 g L-TRY or P over a 24 hour period prior to the run. No significant difference between the improvements in the L-TRY and P group could be demonstrated. It is concluded that oral L-TRY supplementation does not enhance running performance. PMID- 1428381 TI - Influence of acupuncture on physical performance capacity and haemodynamic parameters. AB - In a single blind study the question as to whether the needling of specific acupuncture points is able to produce an increase in physical performance capacity and better regulation of heart rate and blood pressure was examined. Thirty-six healthy young men were assigned at random to three groups, receiving either actual acupuncture, placebo acupuncture or no stimulation. Performance was determined by means of a spiro-ergometer test which was carried out at the beginning and at the end of five weeks of treatment consisting of one session per week. The subjects from the group which actually received acupuncture were able to increase maximum performance capacity significantly and also physical performance at the anaerobic threshold. This may be interpreted as a sign of functional improvement in haemodynamic and metabolic mechanisms. There was, on the whole, no noticeable effect produced by the placebo acupuncture. The control group, which received no stimulation, showed unfavourable changes in the values obtained compared with the results of the performance test at the commencement of the study. PMID- 1428382 TI - Physical inactivity and depression in the community. Evidence from the Upper Bavarian Field Study. AB - In the Upper Bavarian Field Study a representative community sample of 1,536 persons (from 15 years of age and upwards) was interviewed by research psychiatrists. Twenty-seven percent of the respondents reported taking regular and 26.2% occasional physical exercise. Physical inactivity as well as depression were significantly associated with the female gender, increasing age, low socioeconomic status and the presence of a somatic disorder. Using a logistic regression model, the relation between physical activity and depression was measured by the odds ratio with subjects reporting regular physical activity as the reference group. Cross-sectional analysis revealed that after controlling for potential confounder variables the odds ratio for depression was, at 3.15, significantly higher for the physically inactive compared to the regular exercisers. The odds ratio for the group practising occasionally (1.55) was also elevated but not statistically significant, 87.3% of the subjects who participated in the baseline study were reinterviewed five years later. In contrast to the cross-sectional findings, low physical activity at wave 1 was not a risk factor for developing depression at wave 2. PMID- 1428383 TI - Psychological effects during reduced training volume and intensity in distance runners. AB - Improved mood state has ben linked with reduced training (RT). However, RT has been measured only as a reduction in training volume, either maintaining or not considering the intensity of training employed. To investigate the effects of a 4 week reduction in both training volume and intensity on running performance and mood state, 10 well-trained adult male runners trained for 4 weeks at baseline training distance and pace (BT), followed by 4 weeks training reduced in volume by 66%, with intensity diminished so that all workouts were below 70% VO2max. Subjects completed the Profile of Mood States (POMS) before BT (PREBT), before RT (PRERT), and after RT (POSRT). They ran 5 km time trials PRERT and POSRT. Comparisons were made for the positive mood state of Vigor with an average of the values for the 5 negative mood states (NM) of the POMS. Eight of 10 changes from PRERT to POSRT were toward more negative mood. Nine of 10 runners required more time for the 5 km run POSRT than PRERT. Overall, 7 of 10 runners exhibited both an increase in 5 km time and a change toward more negative mood state (p < .004). However, the magnitudes of these changes were unrelated. These results suggest that mood state and running performance may be linked. Moreover, because mood state did not improve, this study suggests that studies dealing with the topic of reduced training should be specific with regard to the influence of both training intensity and volume. PMID- 1428384 TI - Contextual issues for vocational placement coordinators: some preliminary findings. AB - While vocational placement is seen as an important component of the rehabilitation process, the experience of being a vocational placement officer has not been well documented in New Zealand. In the present study, previously developed and validated measures of occupational stress (defined as responsibility pressure, quality concern, role conflict, and job vs non-job conflict) and general life satisfaction were completed by 16 vocational placement officers employed by the Accident Compensation Corporation. Subjects also completed two open-ended questions assessing significant stresses in their work and strategies whereby stress could be reduced. There were high negative correlations between job stress and life satisfaction, and subjects reported particularly high levels of role conflict in their work. Open-ended stresses identified by subjects included: time pressure/workload problems; difficulties with negative societal and employer attitudes to disability; problems with clients, and; personal motivation problems. Most strategies for stress reduction that were identified were concerned with creating more effective communication and decision making processes in the organizational environment. Problems and limitations of the present study are addressed and future research directions are identified. PMID- 1428385 TI - Informal caring networks among Chinese elderly with disabilities in Hong Kong. AB - Community care has been a major guiding policy in developing services for the elderly in Hong Kong. It has been assumed that Chinese families tend to have a large caring network to render care in the community. However, in a survey conducted in early 1991, it was found that such caring networks for disabled elderly people were very small and inconsequential. Quite a high proportion of Chinese disabled elderly are living alone in the community, and have a small network for emotional support. Effective measures to promote family care of disabled elderly people are discussed. Two pathways for integrating the formal and informal care sectors are examined in relation to promoting effective practice for the frail elderly living in the community. PMID- 1428386 TI - Economic status of families living with multiple sclerosis. AB - A nation-wide survey of 604 families living with multiple sclerosis was conducted. The sample was recruited through local chapters of the National Multiple Sclerosis Society and the public press. This paper describes the economic impact of the disease on families. There were 427 families in which the woman had multiple sclerosis and 177 families in which the man had the disease. The average duration of the disease was 10 years. Family income was well above the national median income. Thirty-nine per cent of the men and 19% of the women with multiple sclerosis retired because of disability. Income was inadequate to pay for medical expenses in 21% of the families and 25% had inadequate funds to meet basic living expenses. While 80% of the families had health care insurance, for 28% of the families the insurance was inadequate to cover the cost of their illness. The number of children living at home and the amount of health care bills paid out-of-pocket failed to explain why families in the high income group had difficulty meeting their expenses. Factors other than income and proportion of medical expenses covered by insurance determine the economic impact on the family. If health care providers are going to meet all the needs of a family living with multiple sclerosis, a more comprehensive assessment of their economic status is needed. PMID- 1428387 TI - Young blind children: towards assessment for rehabilitation. AB - Traditional assumptions about assessment need to be rethought, recast or rejected when blind children are to be assessed. Given that blind children follow a unique developmental route, rehabilitation specialists must take account of the impact of blindness on children and think of them also as clinically a special population. Dependence on standardized tests for the primary information about any child is always suspect; with regard to a blind child it is irresponsible. The authors describe the characteristics of an approach that is both systemic and common-sense. They illustrate it by reference to a new procedure (The Simmons Davidson Developmental Profile) and to a case study. PMID- 1428388 TI - Creating a disability mythology. AB - People with disabilities have, for the most part, failed to identify with each other as a group. This has been detrimental because it has built a sense of isolation when a camaraderie based upon existing commonalities could have been developed. During the past ten to twenty years, there has been a great deal of discussion about appropriate language to use when discussing disability issues. This discussion has been a part of a larger debate concerning the existence of a disability culture. I believe that there is indeed a disability culture and I am a proponent of identifying and passing on stories which contribute to that culture. I have chosen to use mythology to convey this message and have begun with a focus on heroes - people who do something out of the ordinary. It is contended that almost all people with disabilities have performed heroic activities because of the pervasive discrimination encountered by each individual with a disability. Creating a disability mythology is an attempt to recognize and promote heroes within the disabled community and to advocate the importance of telling other people how positive change has occurred through instances of individual heroism. PMID- 1428389 TI - Stress amongst teachers of children with mental handicaps. PMID- 1428390 TI - Influence of alcohol intake on the course and consequences of spinal cord injury. PMID- 1428391 TI - Walking after stroke: comfortable versus maximum safe speed. PMID- 1428392 TI - Lateral trunk flexion strength: impairment, measurement reliability and implications following unilateral brain lesion. PMID- 1428393 TI - Long-term effects of exercise training and hyperalimentation in adult cystic fibrosis patients with severe pulmonary dysfunction. PMID- 1428394 TI - Psychosocial dysfunction in adults with epilepsy. PMID- 1428395 TI - Accuracy and variability in response methods used to determine object location knowledge in the blind. PMID- 1428396 TI - T-cell-receptor isoforms. AB - Early work on T-cell hybridomas lacking the T-cell-receptor (TCR) sub-unit CD3 eta had suggested a correlation between the presence of CD3 zeta-eta heterodimers and signalling leading to phosphatidyl-inositol (PI) turnover as well as activation-induced cell death. The cloning of CD3 eta has now allowed thorough and direct analysis of the signal transduction properties of CD3 zeta-zeta-, CD3 zeta-eta- and CD3 eta-eta-containing TCRs. We have found that all forms of the TCR are capable of transducing signals leading to PI turnover, Ca2+ mobilization, IL-2 production and cell-cycle arrest. CD3 zeta and CD3 eta utilize the same promoter which yields coordinate expression of both products, so that restricted CD3 eta expression in a sub-population of thymocytes is unlikely. Immunohistochemical methods employing an anti-CD3 eta-specific monoclonal antibody (MAb) show no detectable staining of thymic sections from adult mice, implying at best a low level of constitutive CD3 eta expression. In contrast, CD3 eta expression is readily detected in the majority of cortical thymocytes of CD3 eta transgenic mice using a Thy-1 promoter construct. However, over-expression of CD3 eta in mice transgenic for this polypeptide does not result in increased negative selection in vivo, consistent with the in vitro findings that induction of cell death is not strictly dependent on CD3 eta. Despite earlier reports of the detection of human CD3 eta protein, we find no CD3 eta message in human thymus or T cells. Cloning of the human CD zeta-eta genomic locus has demonstrated approximately 70% homology between the mouse and human genomic sequence, corresponding to the mouse CD3 eta-specific exon. However, translation of the DNA sequence does not result in a homologous amino acid sequence. Thus, there does not appear to be a CD3 eta protein in humans. PMID- 1428397 TI - Structure and function of the CD16:zeta:gamma complex expressed on human natural killer cells. AB - Natural-killer (NK) cells are large granular lymphocytes involved in host defense against tumor cells and virally-infected cells. In addition to natural cytotoxicity, NK cells can effect antibody-dependent cytotoxicity mediated by CD16 (Fc gamma RIIIA alpha). It has recently been shown that CD16 is associated with disulfide-linked dimers composed of 2 homologous sub-units, zeta and gamma. These transducing molecules are also associated with other multimeric cell surface receptors such as the T-cell antigen receptor (CD3:TCR) complex (zeta and gamma) and the high-affinity Fc receptor for IgE (Fc epsilon RI) expressed on basophils and mast cells (gamma). These results show that distinct cell-surface receptors utilize common transducing sub-units, and emphasize the homology between the CD16, Fc epsilon RI and CD3:TCR complexes. However within the lymphoid cells, the gamma-gamma homodimer is preferentially expressed in NK cells and cytotoxic T cells, suggesting that specific combinations of these transducing dimers might sub-serve distinct signal-transducing functions, and contribute to lymphocyte heterogeneity. PMID- 1428399 TI - Mechanisms of lymphocyte traffic and cell targeting. AB - Several concepts in the immunotherapy of cancer aim to exploit the powerful cellular effector mechanisms of the immune system. In contrast to antibodies and other soluble agents, cells do not distribute randomly with the circulation but have their own program of trafficking through the body and entering the various organs. Some characteristics of migration and homing of different populations of lymphocytes as well as the molecular mechanisms governing lymphocyte entry into tissues are discussed here in order to delineate problems and prospects in targeting cell populations into specific organs. PMID- 1428398 TI - Targeting of T or NK lymphocytes against tumor cells by bispecific monoclonal antibodies: role of different triggering molecules. AB - MAbs directed against triggering surface molecules expressed by T lymphocytes (CD3, TCR, CD2, CD28) or by NK cells (CD2, CD16) are able to induce the functional program of these cells. These MAbs represent suitable reagents to construct biMAbs directed against TAA, in order to specifically target effector lymphocytes against tumor cells. Anti-CD3/anti-EGF-R biMAbs were constructed to specifically direct T lymphocytes against EGF-R+ tumor cells. Such biMAb are able to induce cytolysis of EGF-R+ tumor cell lines (A431, IGROV, KATO-III and U-87) by cytolytic CD3+ effector lymphocytes while tumor cells having low or absent expression of EGF-R were not lysed. In addition, both cytolytic T (CD8+) cells and non-cytolytic (CD4+) IL-2-expanded lymphocytes were able to secrete lymphokines upon contact with EGF-R+ tumor cells. To target NK cells against NK resistant ovarian carcinomas, we used an anti-CD16 Mab (IgG1) together with an anti-ovarian carcinoma MAb (IgG2a), to construct biMAbs using the hybrid hybridoma technique. The hybrid IgG1/IgG2a biMAb triggered the specific lysis of relevant target cells by resting NK cells and by a subset of NK clones. In addition, some TCR gamma/delta+ clones but not TCR alpha/beta+ clones could be targeted by the biMAb. PMID- 1428401 TI - Activation of T cells in vivo using anti-CD3 and staphylococcal enterotoxins. AB - One of the major problems in clinical immunity is that neoplastic and virally infected cells are insufficiently immunogenic to trigger an immune response. During the past several years, our laboratory has explored the use of T-cell specific reagents including monoclonal antibodies (MAbs) and staphylococcal enterotoxins to amplify immune responses. This report summarizes our efforts to augment immunity with these agents. PMID- 1428400 TI - Targeted cytokine production. AB - It has been well established that bispecific antibodies containing anti-T-cell receptor MAbs crosslinked to anti-tumor MAbs induce T cells to lyse tumor cells, as measured in a 51Cr-release assay. Such lysis requires direct attachment between target and cytotoxic cells and most probably involves the exocytosis of cytolytic substances into the cell:cell interface. In addition, targeted T cells mediate a second activity, the secretion into the medium of factors that can block the growth of bound tumor cells and unbound bystander cells. In order to test how targeted effector cells mediate anti-tumor effects in vivo, we are currently developing a totally syngeneic murine system in which murine T cells are targeted against mouse mammary tumors. The system allows us to treat both primary tumors and tumor transplants, using a mammary-tumor-virus antigen as the entity that is specifically recognized on the tumor cells. PMID- 1428402 TI - Possible targets on carcinoma for bMAb retargeting of lymphocyte or drug cytotoxicity. AB - Retargeting of drugs or lymphocyte cytotoxicity through bi-specific monoclonal antibodies (bMAbs) has been proven a therapeutic tool against human carcinoma both in pre-clinical in vitro and in vivo studies. Some of these reagents have already been introduced into clinical trials and preliminary results appear to be promising. However, improvement of the specificity of this approach could be achieved by selecting more suitable target molecules on tumor cells. The research focused on developing MAbs directed against molecules with tumor-restricted distribution and homogeneous expression. Cell-membrane receptors for nutrients or growth factors which operationally represent tumor-specific molecules due to their overexpression, could be considered appropriate targets. Several bMAb anti nutrients (the folate-binding protein) or growth-factor receptor (c-erbB1, c erbB2)/anti-triggering molecules have been generated and all were able to efficiently retarget the relevant population of lymphocytes on tumor cells. In order to design a more reliable and selective therapeutic tool, the following parameters were analyzed: correlation between cytotoxicity and antigen level, potency and possible modulation of the target molecule. PMID- 1428404 TI - Janusin: new molecular design for bispecific reagents. AB - It is well established that soluble CD4 (sCD4) inhibits HIV infection in vitro, regardless of the virus strain or genetic variant. Most effective molecules, thus far, based on sCD4 are those in which CD4 is combined with immunoglobulin constant regions (CD4-IgG or CD4-IgM). Such molecules maintained HIV-gp120 specificity mediated by CD4 and also antibody effector functions such as complement activation, Fc receptor binding, long serum half-life or transport across the placental barrier. We have now developed sCD4 molecules which are even more potent anti-HIV reagents. These molecules are based on the principle of bispecific antibodies and they have properties capable of retargeting cytotoxic T lymphocytes onto HIV-infected cells and inducing efficient killing. CD4 combined with anti-human CD3 (FvCD3) single-chain combining site has been produced (CD4 FvCD3-JANUSIN). This molecule shows the expected biological activities, namely, binding to the 2 ligands, human CD3 and gp120, also efficiently retargeting CTLs of any specificity onto HIV-infected cells. In addition, several advantages over classical bispecific antibodies can be achieved: only one polypeptide, not a mixture containing the desired product, is produced, thus simplifying the purification process. In addition, Janusin designs do not contain the Ig Fc portion, which could mediate illegitimate retargeting of T-cells. In addition to CD4-FvCD3-JANUSIN, receptor-Fv, Fv-Fv or ligand-Fv Janusins can be produced. PMID- 1428403 TI - Engineering a humanized bispecific F(ab')2 fragment for improved binding to T cells. AB - We recently constructed a humanized bispecific antibody (BsF(ab')2v1) by separate E. coli expression of each Fab' arm followed by directed chemical coupling in vitro. BsF(ab')2 v1 (anti-CD3/anti-p185HER2) was demonstrated to retarget the cytotoxic activity of human CD3+ CTL in vitro against the human breast-tumor cell line, SK-BR-3, which over-expresses the p185HER2 product of the proto-oncogene HER2. Our minimalistic humanization strategy is to install as few murine residues as possible into a human antibody in order to recruit antigen-binding affinity and biological properties comparable to that of the murine parent antibody. This strategy proved very successful for the anti-p185HER2 arm of BsF(ab')2 v1. In contrast BsF(ab')2 v1 binds to T cells via its anti-CD3 arm much less efficiently than does the chimeric BsF(ab')2 which contains the variable domains of the murine parent anti-CD3 antibody. Here we have constructed additional BsF(ab')2 fragments containing variant anti-CD3 arms with selected amino acid replacements in an attempt to improve antibody binding to T cells. One such variant, BsF(ab')2 v9, was created by replacing 6 residues in the second hypervariable loop of the anti-CD3 heavy chain variable domain of BsF(ab')2 v1 with their counterparts from the murine parent anti-CD3 antibody. BsF(ab')2 v9 binds to T cells (Jurkat) much more efficiently than does BsF(ab')2 v1 and almost as efficiently as the chimeric BsF(ab')2. This improvement in the efficiency of T-cell binding of the humanized BsF(ab')2 is an important step in its development as a potential therapeutic agent for the treatment of p185HER2 over-expressing cancers. PMID- 1428405 TI - Functional assembly of chimeric T-cell receptor chains. AB - We have generated cytotoxic T-cell hybridomas expressing chimeric T-cell receptors (cTCR) with an antibody-type specificity for the TNP hapten. Transfectants expressing the cTCR genes could mediate specific lysis of haptenated tumor cell lines of various types and secrete IL-2 upon stimulation with TNP modified cells. In a previous report, we showed that double-gene transfectants expressing either VHC alpha and VLC beta or VHC beta and VLC alpha could be activated by TNP-modified stimulator cells or TNP proteins immobilized on plastic. Single-chain transfectants (expressing VHC alpha or VHC beta alone) could be mainly activated by TNP-cells. We now report that transfection of chimeric VHC alpha gene into an alpha-chain-defective mutant restores the surface expression of the TCR/CD3 complex. In parallel, such transfectants regained the ability to respond to mitogen and anti-CD3 antibodies and responded weakly to TNP cells. Double gene transfectants, bearing 2 complementary chimeric chains, expressed high amounts of cTCR on their surface, sufficient to acquire sound anti TNP reactivity. Cells expressing the VHC beta gene only were not functional and had no detectable surface TCR chains. Taken together, our results suggest that chimeric VHC alpha chains can pair with endogenous V beta C beta chains, but that there is preferential association between complementary chimeric chains, resulting in higher functional expression of the chimeric TCR. PMID- 1428406 TI - Bispecific-antibody-mediated targeting of radiolabeled bivalent haptens: theoretical, experimental and clinical results. AB - Chemically conjugated bispecific (anti-cell surface antigen, anti-hapten) Fab' Fab antibodies (Bs-MAbs) have been used to target 125I-, 111In- and 99mTc-labeled haptens to cell sub-sets. In vitro, bivalent haptens were found to bind more strongly than their monovalent analogs to the Bs-MAbs bound to ("ordered" on) the cell surface, or than to free ("disordered") Bs-MAbs: they are selective for cell bound Bs-MAbs. In tumor-grafted nude mice models, the sequential injections of microgram amounts of Bs-MAb, and 1 day later, of microC amounts of bivalent haptens permits to sharply delineate small tumors (using a gamma camera), hours after injection. Further, the isotope biodistribution was found to be at least 3 times more selective for the tumor than that obtained with directly labeled anti CEA F(ab)'2 or with monovalent haptens. This better in vivo selectivity of the 2 step targeting of bivalent haptens was also demonstrated in a pharmacokinetic study using therapeutic amounts of reagents. In primary-colon-carcinoma patients, a similar comparative immunoscintigraphy study confirmed the better selectivity of bivalent hapten targeting over direct targeting, on the basis of image quality and ex vivo tissue counting. In patients with medullary carcinoma of the thyroid, bivalent hapten targeting allowed us to confirm tumor extension and to find occult lesions. Interestingly, radio-immunoguided surgery was necessary to resect these small lesions. These experimental results, together with technological and theoretical considerations, suggest that Bs-MAb-mediated targeting of isotopes (or other agents) is one of the major ways to increase the clinical performance of MAb-based targeting diagnostic and therapeutic tools. PMID- 1428407 TI - Novel surface molecules involved in human NK cell activation and triggering of the lytic machinery. AB - Three new monoclonal antibodies (MAbs) termed 7A6, PP35 and A6/143 were isolated after mouse immunization with CD3- CD16+ NK clones. The screening procedure was based on the ability of MAbs to trigger cytolytic activity of the immunizing clones in a re-directed killing assay against the P815 murine mastocytoma cell line. The 7A6 MAb reacts with 58 kDa surface molecules that appear to belong to the same molecular family defined by the previously described NK-sub-set-specific GL183 and EB6 MAbs. However, unlike from these MAbs, the 7A6 MAb reacted with (and activated) all CD3- NK lymphocytes, independent of their sub-set assignment (based on the expression or lack of expression of EB6, GL183 and CD16). The PP35 MAb reacted with a 70 kDa surface molecule expressed on all CD3- NK cells, as well as on TCR gamma/delta + cells and on a small sub-set of TCR alpha/beta + CD8+ lymphocytes. The PP35 MAb induced activation of essentially all NK cells, although clonal analysis revealed quantitative differences in the magnitude of the cytolytic responses elicited in different clones. Finally, the A6/143 MAb reacted with a molecule of 115 kDa expressed by all human PBL. Similarly to 7A6 and PP35 MAbs, the A6/143 MAb activated all sub-sets of cloned NK cells. PMID- 1428408 TI - Bispecific IgG and IL-2 therapy of a syngeneic B-cell lymphoma in immunocompetent mice. AB - Bispecific antibody (bsAb) which binds to CD3 and a tumor-associated antigen can induce lysis of tumor cells by T cells. Lymphocytes targeted by bsAbs are also capable of inhibiting the growth of human xenografts in athymic mice. However, little is known about the impact of this form of therapy in immunologically intact animals. The 38C13 murine B-cell lymphoma model is well suited for the study of bsAb therapy. BsAb, consisting of an IgG that is monospecific for both CD3 and the idiotype expressed by V 38C13 cells, was obtained from hybrid hybridoma supernatant. Immunocompetent C3H mice were inoculated with V 38C13 cells and treated 2 days later with antibody. Over 90% of mice treated with monospecific antibody died of lymphoma, while only 27% of mice treated with bsAb developed tumor and died. In studies of bsAb/IL-2 synergy, treatment was delayed until 5 days after inoculation to allow for a larger tumor burden at the time of treatment. IL-2 was administered on days 3 to 6. All mice treated with IL-2 alone died of lymphoma, as did 75% of mice treated with bsAb alone. Only 18% of mice treated with both bsAb and IL-2 developed lymphoma. Thus, therapy with bsAb and IL-2 eliminated a tumor load 100- to 1000-fold greater than can be eliminated by therapy with anti-tumor antibody alone. These studies demonstrate the value of using immunocompetent animal models, and support the further exploration of bsAbs as an immunotherapy for human malignancy. PMID- 1428409 TI - Bispecific antibody therapy of two murine B-cell lymphomas. AB - Numerous in vitro studies have shown that T lymphocytes can be targeted towards any target cell by using bispecific antibodies (bsAbs) with specificity of the CD3/TCR complex and a target cell antigen. We have produced bsAbs directed against the membrane expressed idiotype of the murine B cell lymphomas BCLI and 38C13, and murine CD3 complex. The dual specificity of the hybrid-hybridoma produced monoclonal antibodies (MAbs) could be demonstrated by flow cytometry, the induction of T cell proliferation, the induction of IL2 secretion by polyclonal T cells, and redirected lysis of the relevant target cells. Immunotherapy of tumor bearing animals demonstrated that bsAbs could efficiently target T cells towards the tumor cells, that tumor cell--T cell bridging is established in vivo, and that both T cell subsets contribute to tumor regression resulting in long-term survival and cure of the lymphomas. PMID- 1428410 TI - CD4 immunoadhesins in anti-HIV therapy: new developments. AB - CD4, the cell-surface receptor for the human immunodeficiency virus (HIV), is a member of the immunoglobulin (Ig) gene superfamily. It contains 4 extracellular sequences homologous to Ig variable domains, the first of which (V1) is sufficient for binding to HIV. To develop CD4 as an anti-HIV therapeutic, we engineered a CD4 immunoadhesin (CD4-IgG)--a fusion protein containing the V1 and V2 domains of CD4 with the hinge and Fc regions of human Ig heavy chain. A chimeric protein of this type has several advantages compared to the soluble receptor, including a greatly extended in vivo half-life and greater avidity for HIV; moreover, like an antibody, it performs effector functions via its Fc domains, such as complement activation and antibody-dependent cell-mediated cytotoxicity. In vivo experiments show that CD4-IgG protects against HIV-I IIIB infection of chimpanzees when administered prior to viral challenge. In addition, CD4-IgG is transferred efficiently across the placenta from mother to fetus in rhesus monkeys. To evaluate its safety in humans, we conducted a phase-I clinical trial in adult patients with AIDS and AIDS-related complex. We found that, in a total of 16 patients, administration of CD4-IgG was well tolerated at doses up to 1000 micrograms/kg of body weight, with no important clinical or immunological toxicities noted. Given its unique properties, particularly the ability of CD4 IgG to cross the placenta, we plan to focus future clinical efforts on preventing infection of newborns via maternal-fetal transfer of HIV. PMID- 1428412 TI - Adoptive immunotherapy of ovarian carcinoma with bs-MAb-targeted lymphocytes: a multicenter study. AB - A bispecific monoclonal antibody (bs-MAb) (OC/TR) was produced in large quantities for the intraperitoneal (i.p.) treatment of ovarian cancer. The bs-MAb recognizes the folate-binding protein on ovarian cancer cells on the one hand and the CD3 activation site on T lymphocytes on the other. T lymphocytes were expanded ex vivo, targeted with OC/TR in vitro and administered to the i.p. cavity in the presence of soluble OC/TR. All patients developed human anti-mouse antibodies (HAMA). In the Dutch study, 2 complete remissions (CR) were seen, 2 partial regressions (PR), I stable disease (SD) and I progressive disease (PD). In the Italian study 3 CR, I PR, I SD and 2 PD were seen. PMID- 1428411 TI - Initial experience in treating human lymphoma with a combination of bispecific antibody and saporin. AB - Results are presented showing the use of bispecific F(ab')2 antibodies (bsAbs) in the delivery of saporin for the treatment of 2 human B-cell malignancies. BsAbs delivering saporin through CD22, but not through CD19, were effective at inhibiting the uptake of [3H]leucine by Daudi and Raji cells. Furthermore, a combination of 2 anti-CD22 bsAbs, selected to bind simultaneously to saporin, bound saporin 20 times more avidly and inhibited protein synthesis far more efficiently than any single bsAb. In the first patient, with end-stage chronic lymphocytic leukaemia (CLL), treatment with 10 mg of saporin complexed to 100 mg of anti-CD19 bsAb over 43 days showed no therapeutic effect. In contrast, the second patient, with end-stage non-Hodgkin's lymphoma (NHL), given 5 mg of saporin complexed with a pair (50 mg) of anti-CD22 bsAbs over 15 days showed a marked clinical response, including complete clearance of tumour from the blood, clearance of ascites and shrinkage of tumour masses. Neither patient experienced any toxic side-effects, either during or after treatment. However, the second patient developed a strong anti-mouse Fab (HAMA) response 28 days after the treatment started. No anti-saporin response could be detected. PMID- 1428413 TI - Response of fetal and newborn piglets to maternal protein restriction during early or late pregnancy. AB - Dietary protein restriction during pregnancy has an adverse effect on progeny development, although the importance of the time at which the nutritional insult occurs is unclear. The objective in our study was to test the hypothesis that severe protein restriction during the first trimester of swine pregnancy has a greater detrimental effect on fetal development than restriction in late pregnancy. On the day of mating, primiparous swine were assigned to control (C, 13% protein) or protein-restricted (PR, 0.5% protein) diets and fed in 4 regimens: 1) C diet throughout pregnancy (114 +/- 2 days) (n = 5), 2) PR diet to day 44, C diet to parturition (n = 6), 3) C diet to day 80, PR diet to parturition (n = 8), and 4) PR diet throughout pregnancy (n = 6). In addition, 6 pigs fed C and 7 pigs fed PR diets were killed at day 44 to assess placental and fetal development. Maternal diet had no effect on placental or fetal weight, crown-rump length, or heart girth circumference in 44-day fetuses. Mean birth weight of newborn piglets was 1462, 1291, 1262, and 1064 g for C, PR:C, C:PR, and PR groups, respectively (C greater than PR:C = C:PR greater than PR, p less than 0.01). Plasma total protein and albumin were less (p less than 0.01) in PR than in PR:C and C:PR; all three groups were less than C (p less than 0.01). Liver weight and total liver protein, RNA, and DNA followed the same pattern (C greater than PR:C = C:PR greater than PR, p less than 0.05). Longissimus muscle total protein, RNA, and DNA were greater in group C than in all other groups (p less than 0.01). Maternal protein restriction during early pregnancy produced less developmental impairment than restriction throughout pregnancy, but the magnitude of impairment was similar to that produced by restriction during only the third trimester. The effects of early restriction were manifested at birth, even though none of the indices of stunting were observed at 44 days when the maternal protein restriction was ended. Whether the effects of early versus late restriction show the same mechanism of action has not been determined. PMID- 1428414 TI - A non-invasive technique for the accurate measurement of leg length in animals. AB - A novel, non-invasive technique for accurate measurements in animals (Kyniklometry) is presented. Kyniklometry (derived from greek o kuvikloz the rabbit) determines the distance between soft tissue landmarks in conscious rabbits, in particular the rear lower leg. Each measurement consists of six subsequent and independent estimations of this distance, with a technical error of 79 microns (study I), respectively 83 microns (study II). The angle of the relaxed sitting animal's knee is approximately 45 infinity, and remains individually almost constant during subsequent measurements. The precision of the device was compared with X-ray stereophotogrammetry (technical error 30 microns). Five female New Zealand White rabbits were measured for 13 consecutive days at 24 hour-intervals both by kyniklometry and X-ray stereophotogrammetry (study I). The mean increment of 5 kyniklometric series of ten (3rd to 13th day) 24-hour increments was 0.988 mm, the mean 24-hour-variance was 0.244 mm2. Sixty point five percent of this variance could be explained by parallel right/left leg soft tissue variation. Only 5% of the variance was explicable by the technical error. The 24-hour-correlation between kyniklometry and X-ray stereophotogrammetry was significant with r = 0.889 and p less than 0.001. Kyniklometric measurements were also performed in 5 female rabbits for 56 days at 24-hour-intervals (study II). We found spontaneous periodicity once every 8 to 14 days. There was a diurnal variation of rear lower leg increment with maxima in the early morning hours. PMID- 1428416 TI - Relation between brain and body growth in allied rats. AB - Cranial volumes were measured from museum specimens of wild-caught and laboratory born Allied rats from eastern Australia. The relation of these volumes to body weight and body length, and also to age at death in the laboratory-reared sample, was determined. Growth of both brain and body was rapid during the first three postnatal months and slowed markedly over the next month, but appeared to continue at a very slow rate throughout life. In particular, the major surge in brain growth occurred in the first three postnatal weeks. Modified Gompertzian growth functions describe the pattern of growth quite well, though the nature of the data precluded highly sensitive fits. Three features were clear: 1) the rate of slowing of growth was about the same for all variables, 2) growth appeared to continue throughout the life of the animal, and 3) the trajectory of brain growth led that of body growth by about four days. The pattern of growth in Allied rats is similar to that of laboratory rats and probably to those in other murids. PMID- 1428415 TI - Expression of transforming growth factor-beta (TGF-beta 1) and insulin-like growth factor II (IGF-II) messenger RNA in the developing subcutaneous tissue (SQ) of the fetal pig. AB - Studies (in situ hybridization) were performed on the developing subcutaneous tissue (SQ) of the pig fetus to determine sites of synthesis of TGF-beta 1 and IGF-II. Tissues from 50, 70, 90, 110-day-old pig fetuses and 7-day-old postnatal pigs were Bouin's fixed, paraffin embedded and hybridized with biotin labelled cDNA probes. The expression of TGF-beta 1 messenger RNA was detectable primarily in the dermis, hair follicle fat lobule, outer and inner SQ areas at all ages. Cells adjacent to adipocyte clusters and some small adipocytes were positive for TGF-beta 1. There was no positive hybridization of TGF-beta 1 probes in the developing muscle below the SQ. The expression of IGF-II was evident in the developing muscle below the SQ at 50 d and 70 d, and could be detected in the outer and inner SQ at 70 d. Much lower levels of IGF-II expression were observed in 90 and 110 d fetuses, but an increase in IGF-II expression was evident in the muscle of 7d postnatal pigs. Our results suggest that paracrine and autocrine regulatory systems may be operative for developing adipocytes (TGF-beta 1) and muscle (IGF-II), with specific areas and times of TGF-beta 1 and IGF-II expression being evident in developing pig SQ tissue. PMID- 1428417 TI - Effects of surgical decapitation and chicken growth hormone (cGH) replacement therapy on chick embryo growth. AB - The effects of decapitation and chicken growth hormone (cGH) replacement therapy on chick embryo growth has been investigated. Removal of the prosencephalon at 33 38 hrs (1.38 to 1.58 Days) of incubation decreased body (torso) and liver weights as well as skeletal growth as indicated by tibial length. A single pituitary gland transplanted onto the chorioallantoic membrane (CAM) partially restored torso growth and completely reversed the increase in body water content which characterizes decapitated embryos. Replacement therapy with cGH did not influence body weight but did, on Day 16.5 of incubation, increase tibial length and liver DNA content and concentration. These latter findings suggest that there may be limited hypothalamoadenohypophyseal (GH) axis function in the chick embryo. The effects of decapitation on torso growth are also discussed in conjunction with decapitation effects on albumen swallowing (absorption) and yolk absorption. PMID- 1428418 TI - Sexual cranial dimorphism in malnourished rats treated with growth hormone. AB - One hundred and sixty two Holtzman rats of both sexes were malnourished during suckling and post-weaning periods. Some of them received periodic injections of growth hormone. After sampling, at 56 days of age, skulls were cleaned and measured. Differences within and between sexes were estimated by Mahalanobis D2 distances. Normal cranial differentiation between sexes (SCD) was decreased by malnutrition and restored by growth hormone treatment. The effect of the growth hormone on skull size was larger in malnourished males than females. This differential increment between sexes explains how growth hormone acted on the restoration of SCD. PMID- 1428419 TI - Schizophrenia as a contingent risk factor for criminal violence. PMID- 1428420 TI - Coercion in civil commitment: process, preferences, and outcome. PMID- 1428421 TI - Psychotic versus nonpsychotic misdemeanants in a large county jail: an analysis of pretrial treatment by the legal system. AB - There are significant numbers of mentally ill men and women in jail and the level of their psychopathology is often serious. Once in jail, the psychotic individual is subjected to conditions conducive to further decompensation and higher suicide rates. If this is the case, the duration of confinement--that is, the duration of exposure to this toxic environment--is not trivial. Of further concern, from the standpoint of due process, would be the duration of confinement prior to any determination of guilt or innocence. Therefore, it makes sense to examine what happens to jailed psychotic individuals as they wait for trial. Our experience suggested that pretrial jail time, even for minor offenses, is lengthy. The central hypothesis of our study, then, was that psychotic men, charged with misdemeanor offenses, would be incarcerated for significantly longer periods of time, prior to trial, than their nonpsychotic fellows. Descriptive data was also collected. PMID- 1428422 TI - Psychiatrists and the parameters of expert testimony. PMID- 1428423 TI - A comparison of criminal recidivism among schizophrenic and nonschizophrenic offenders. PMID- 1428424 TI - Law, rights, and psychiatry in the People's Republic of China. PMID- 1428425 TI - Toxic epidermal necrolysis. PMID- 1428426 TI - Wart, keratoacanthoma, and squamous cell carcinoma: a spectrum of the same neoplastic process? PMID- 1428427 TI - Smoking and the skin. PMID- 1428428 TI - Porokeratosis in immunosuppressed and nonimmunosuppressed patients. AB - Porokeratosis is an uncommon, inherited, autosomally dominant disorder. In the last decade association of porokeratosis and immunosuppression has been observed. In this study we carried out a comparative study between immunosuppressed and nonimmunosuppressed porokeratosis cases. We found that 9 out of 20 cases of porokeratosis were associated with organ transplantation/immunosuppression. Clinicopathologic study revealed that the pattern of disease is alike both in immunosuppressed and nonimmunosuppressed patients. Our observations indicate that immune modulation could be a factor in the genesis of porokeratosis. PMID- 1428429 TI - Candida albicans--saprophyte or pathogen? AB - Skin scrapings taken from toe spaces of 200 healthy volunteers and from toe webs and groins of 150 pediatric patients were cultured for Candida albicans using the serum germ-tube test. The results showed that Candida albicans can be isolated in about 15% of normal toe spaces and 14% of children with normal groins. Although Candida albicans can be found in various grades of athlete's foot and also in some abnormal groins, we believe that it is not necessarily responsible for these conditions and is often present at these sites only as a saprophyte. PMID- 1428430 TI - Hemostasis and platelet aggregation in purpuric pigmented angiodermatitis eruptions. AB - Ten patients with chronic purpuric and pigmented angiodermatitis in the extremities and two patients with acute and disseminated eczematoid-like purpura angiodermatitis were studied with current hemostasis parameters: (1) platelet aggregation, (2) platelet circulating aggregates, (3) clotting factor measurements and high molecular weight kininogen (HMWK) in their coagulation fraction. The results showed: (1) reactional thrombocytosis with morphologic changes; (2) increased levels of platelet circulating aggregates; (3) increased response of platelet aggregation to different agonists, especially at very low doses, and also when we used washed platelets resuspended in normal plasma; (4) delayed activation of the contact system; (5) decrease of the activity of the fibrinolysis activators; and (6) diminished function activity of the HMWK coagulation fraction. As a physiopathogenic hypothesis in these patients, there is a cutaneous pathology that could be entailed to these hematologic alterations of the platelet-HMWK-endothelial cells-kinins-coagulation-fibrinolysis system. PMID- 1428431 TI - Cutaneous lymphoma. PMID- 1428432 TI - Follicular mucinosis and Hodgkin's disease. PMID- 1428434 TI - Pachydermodactyly transgrediens. PMID- 1428433 TI - Vesiculobullous lupus erythematosus with milial formation. PMID- 1428435 TI - Impact of the new United States medical licensing examination on the certification process of the Educational Commission for Foreign Medical Graduates. PMID- 1428436 TI - Treatment of female androgenetic alopecia with minoxidil 2%. AB - The safety and efficacy of minoxidil 2% for the treatment of female androgenetic alopecia was assessed in a 32-week double-blind placebo-controlled trial. Thirty three women aged 22 to 44 years with hair loss classified as Ludwig's grade I or II were enrolled, and 28 completed the trial. Before the administration of treatment, mean nonvellus hair counts were taken within a 1-cm2 target area of the scalp. For the 15 patients in the minoxidil group, the mean count was 169 hairs compared with 161 hairs for the 13 patients in the placebo group. At the completion of the trial, the patients treated with minoxidil 2% had a mean nonvellus hair count of 195 hairs versus a mean hair count of 177 for patients in the placebo group; 60% (9) of the patients in the minoxidil group showed minimal to moderate hair growth compared with 46% (6) of the patients in the placebo group. No serious side effects were encountered during this study, nor any significant changes in safety parameters. There were no dropouts due to medical events related to minoxidil 2%. PMID- 1428437 TI - Lepromatous leprosy treated with recombinant interferon gamma: cutaneous histologic changes. AB - We report on the histologic changes occurring in single cutaneous lesions, from six active lepromatous patients, 1 week following the administration of three daily intradermal injections, 35 micrograms each, of recombinant interferon gamma (rIFN-gamma). Except for a strong induration at the injection site, rIFN-gamma produced no adverse systemic reactions and was able to promote a remarkable influx of T-lymphocytes, mononuclear phagocytes with large nuclei, nonvacuolated cytoplasm, and reduced lysozyme reactivity. Furthermore, despite no clear-cut reduction of mycobacterial dermal burden, bacilli showed a clear increase in the granular appearance. Present findings provide a basis for further elucidation of rIFN-gamma as an additional tool for leprosy treatment. PMID- 1428438 TI - Coexistence of familial systemic lupus erythematosus and localized scleroderma. PMID- 1428440 TI - The porphyrias. PMID- 1428439 TI - Localized scleroderma and Borrelia antibody seroconversion. PMID- 1428442 TI - Sunscreens, UVA, and cutaneous malignancy: adding fuel to the fire. PMID- 1428441 TI - A concise guide to topical sunscreens: state of the art. PMID- 1428443 TI - Calcipotriol and psoriasis. PMID- 1428444 TI - The rare coexistence of leprosy and psoriasis. PMID- 1428446 TI - Incidence of skin disease in Cuzco, Peru. AB - In the nations of the developing world, the incidence of skin disease is especially affected by geography. While most studies focus on the tropics, this report records the pattern of skin diseases encountered in a South American mountain city. Among 1277 patients examined, the noninfectious dermatoses predominated. PMID- 1428445 TI - Pattern of skin diseases at the National Skin Centre (Singapore) from 1989-1990. AB - At the National Skin Centre, 74,589 new attendances were seen from 1989 to 1990. The M:F ratio was 1:1. The majority of the patients belonged to the 20-39 year age groups (40%). Frequencies of psoriasis (20.4%) and alopecia (17.2%) were higher among Indians; exfoliative dermatitis was higher among Malays (19.72%); and insect bites were higher among Chinese (87%) [P less than 0.05] compared with ethnic distribution (9.9%, 7.6%, and 77.2% respectively) of NSC patient population. Dermatitis (34.2%) and acne (10.9%) were the most common skin disorders seen. The more common dermatoses seen in 1989/90 differ slightly from those reported in 1950s and 1980s; however, the frequencies of contact dermatitis, fungal infection, and insect bite reactions of 5.8%, 10.9%, and 7.6%, respectively, in 1980 have decreased to 4.7%, 5.4%, and 2.3%, respectively, in 1989/90. There was no seasonal variation in the frequency of various dermatoses except for psoriasis, which was more prevalent during the first quarters of 1989 and 1990. Our results showed that the pattern of skin diseases in Singapore is slowly approximating that of developed countries. The changes in the pattern of skin diseases are probably due to improved economic status, better education and hygiene, ready availability of dermatology services, as well as changes in occupational and environmental contactants over the last decade. PMID- 1428447 TI - Chronic cutaneous leishmaniasis: Leishmania parasites in blood. AB - Two patients with chronic cutaneous leishmaniasis had positive blood cultures. The diagnosis was established by the clinical picture, skin biopsy, and culture for Leishmania major and tropica. PMID- 1428448 TI - Cutaneous leishmaniasis in Riyadh region: four-year study of the epidemiologic and clinical features. AB - A retrospective study of 11,802 patient records with cutaneous leishmaniasis in Riyadh region was conducted during the period 1987 to 1990. The following findings resulted from the study. The incidence rate declined from 244.2 to 106.5 per 100,000 population. The infection was mainly among non-Saudi men in their working years. The Saudis represented 33% of the total number of patients. The Saudi patients were mainly young, below 15 years of age, with almost equal men/women distribution. The non-Saudis were found to have more multiple lesions; 65% of them had three or more lesions compared with 10% in Saudis. The lesions were mainly on the exposed parts of the body such as the face (20%), neck (3.3%), upper limbs (23.3%), and lower limbs (15%). Agricultural areas such as Riyadh vicinity, Al-Kharj, Shagraa, and Al-Koweeya showed consistently the highest foci of infections. The infections were highest in winter and lowest in summer. PMID- 1428449 TI - Diffuse cutaneous leishmaniasis with atypical aspects. AB - A 16-year-old man had long-standing diffuse cutaneous leishmaniasis with the following characteristics: diffuse infiltrated lesions rich in amastigotes, absence of mucosal involvement, and lack of parasite-specific cell-mediated immune response. In situ identification of Leishmania mexicana amazonensis was achieved by the use of monoclonal antibodies. Clinically, as an atypical finding there was deep and extensive ulceration in the lower limbs. Histologically, an atypical characteristic was the presence of a high number of eosinophils in the infiltrate predominantly in the ulcerated lesion. Ultrastructurally, parasitized and lysed eosinophils with dispersion of their granules were seen in the vicinity of parasitized or lysed macrophages. PMID- 1428450 TI - Behcet's disease and surgical intervention. AB - Behcet's Disease (BD) is a systemic disorder with an unknown etiopathogenesis. The need for clinical criteria in the establishment of diagnosis is of great importance. We present the case of a 27-year-old man with BD, who had a surgical operation during the active period of his disease and experienced subsequent complications. Cutaneous hyper-reactivity response to minor cutaneous trauma--the pathergy phenomenon--is found in most patients with BD. Theoretically, major traumas may lead to major reactions in the skin or any of the organs. In practice, we observed that while there was a severe inflammatory reaction- histopathologically a superficial perivascular dermatitis--which developed at the incision site, the systemic symptoms of the disease increased in spite of intensive treatment of the condition. PMID- 1428451 TI - Pyoderma gangrenosum: associations revisited. AB - Fourteen cases of pyoderma gangrenosum were seen over a period of 24 years at the Hull Royal Infirmary Dermatology Department. Several associated conditions were found. Seven cases were associated with rheumatoid arthritis of which five were sero-positive, including one with Felty's syndrome. One case was associated with both ulcerative colitis and psoriasis; one with polycythemia rubra vera; two patients had diverticular disease including one who also had rheumatoid arthritis; one had positive syphilis serology. In three cases there was no significant associated disease identified. Ten out of the fourteen cases were women, indicating a female preponderance by a ratio of about 2F:1M; a figure similar to that stated by Seitzinger. The age of presentation ranged from 30 to 80 years. PMID- 1428452 TI - Hair follicle nevus. AB - Four cases of hair follicle nevi are described. Hair follicle nevus is an extremely rare hamartoma occurring on the face, which has had no clear histopathologic definition until now. A short review of the clinicopathologic features of this disease is presented. PMID- 1428453 TI - Acute adult T-cell leukemia/lymphoma presenting with florid cutaneous disease. AB - Adult T-cell leukemia/lymphoma (ATLL) is characterized by cutaneous disease, hypercalcemia, associated HTLV-I infection, and a fulminant course refractory to therapy. A patient with acute ATLL is described, and the natural history of ATLL is reviewed. PMID- 1428454 TI - Pyoderma gangrenosum associated with antiphospholipid antibodies. PMID- 1428456 TI - Pyoderma gangrenosum treated with hyperbaric oxygen therapy. AB - The management of pyoderma gangrenosum often requires systemic drug therapy, such as corticosteroids, sulfones, or immunosuppressants, either alone or in combination. Inconsistent response to therapy is a source of frustration to both patient and physician. Several reports in the literature document the successful treatment of pyoderma gangrenosum with hyperbaric oxygen therapy. In our patient, a woman with severe rheumatoid arthritis and diabetes mellitus, hyperbaric oxygen therapy not only promoted healing of pyoderma gangrenosum but permitted reduction of systemic corticosteroids. PMID- 1428455 TI - Treatment of pyoderma gangrenosum with clofazimine. AB - We report a case of pyoderma gangrenosum in a 80-year-old woman suffering from ulcerative colitis and treated with clofazimine. Significant improvement was evident within 5 days following commencement of therapy, complete healing occurred after only 4 weeks of treatment. PMID- 1428457 TI - Solitary condyloma latum on the umbilicus. PMID- 1428458 TI - Kaposi's sarcoma observed in a young man in 1973. PMID- 1428459 TI - Facial cellulitis-like Sweet's syndrome in acute myelogenous leukemia. PMID- 1428460 TI - Cellular immune effects of thalidomide in actinic prurigo. PMID- 1428461 TI - New approaches to assess topical corticosteroid bioequivalence: pharmacokinetic evaluation. AB - An ideal method for measuring the bioavailability of topical corticosteroids should be simple, accurate, and adaptable to a variety of settings and should not require extensive special training to perform. Drug uptake into the stratum corneum, measured by tapestripping, is correlated with the pharmacodynamic response of skin blanching, observed in the vasoconstrictor assay. Differences in stratum corneum drug uptake can be objectively quantitated as a function of time, occlusion, dose applied, and vehicle. Tapestripping measurements are reproducible within individual subjects, but large interindividual variabilities may exist. The chromameter, a new technology, objectively quantitates color numerically and can be used to measure skin blanching as part of the pharmacodynamic response to topical corticosteroids. The chromameter offers an easy, objective method with which to quantitate the pharmacodynamic response of topical corticosteroids. Both methods allow a more mechanistic approach than currently used methods to investigate topical drug pharmacokinetics and pharmacodynamics. PMID- 1428462 TI - Bioequivalence of topical corticosteroids: a regulatory perspective. AB - After reviewing the history of generic drug substitution policy in the United States, this paper discusses issues of equivalence as they apply to topical drug products. Documentation of bioequivalence of topical products has been problematic, and current methods are being re-evaluated by the Food and Drug Administration. The FDA is currently evaluating various extensions of the basic methodology of the Stoughton-McKenzie vasoconstrictor assay, in order to develop a more comprehensive pharmacodynamic methodology for documenting topical drug bioequivalence. A modern pharmacodynamic model is described, based on nonlinear dose-response relationship, a baseline effect, and a maximum or plateau effect. The Agency's goal is a bioequivalent methodology that will be simple, readily performed, and based on more objective methods of measuring the vasoconstrictor response. PMID- 1428463 TI - Issues in measuring percutaneous absorption of topical corticosteroids. AB - Studies that examine the pharmacokinetics of topical drugs at their site of action in the skin have been difficult to perform and, therefore, limited in number. In the early years of topical drug pharmacokinetic research, investigators had to rely on the measurement of less direct indicators of drug throughput such as blood levels and urinary excretion. Today, advances in theory are impelling pharmacokinetic research in new directions, including the measurement of drug availability in tissue compartments within the skin. This research will lead to greater precision in pharmacokinetic measurement and greater relevance of these measurements to the therapeutic efficacy of topical corticosteroids in cutaneous disease states. PMID- 1428464 TI - The vasoconstrictor assay in bioequivalence testing: practical concerns and recent developments. AB - The vasoconstrictor assay, when properly performed, is a highly reliable method to determine bioequivalence of generic formulations. Recent research has resolved some of the remaining questions concerning the practical application of the assay. Significant vehicle-related differences have been observed between the potency of different, supposedly equivalent formulations now on the market. Large differences in concentrations of the active agent in similar vehicles usually have not resulted in corresponding differences in vasoconstrictor assay results. Finally, the time course of drug effects may differ among highly potent and less potent corticosteroids. In general, the higher the potency of the topical corticosteroid, the earlier the maximal effect is observed. This finding suggests that short application of highly potent agents might minimize systemic absorption without sacrificing efficacy. PMID- 1428465 TI - Bioequivalence studies of topical preparations: statistical considerations. AB - To be approved for marketing, a potential generic pharmaceutical product must demonstrate bioequivalence, that is, a rate and extent of absorption similar to those of the currently marketed ("innovator") product. For oral products, design and statistical analysis for studies conducted to determine whether two products are bioequivalent have become reasonably standardized; the design is crossover, and analysis is based on the two one-sided tests principle. The purpose of this overview is to consider whether the practices for oral products apply to topical products, and where different procedures may be required. The principles behind the practices for oral products are seen, largely, to carry over to topical products. PMID- 1428466 TI - Topical corticosteroids: quality control considerations. AB - A simple procedure is developed, which can be used as a quality control test. The method utilizes commercially available diffusion cell assembly, synthetic membrane, and an appropriate receptor phase. The amount of drug released over time is determined using an HPLC method. From this, the drug release rate, flux, microgram/cm2/min0.5 is calculated. This drug release rate can serve as a good quality control test to assure batch-to-batch uniformity. PMID- 1428467 TI - Clinical trials of topical corticosteroids in psoriasis: correlations with the vasoconstrictor assay. AB - It would be desirable to develop an alternative system to clinical studies to evaluate the potency of generic topical corticosteroids and of new formulations of existing innovator corticosteroids. The vasoconstrictor assay is a reliable method for testing potency; however, its results do not always agree with clinical studies. Psoriasis offers an ideal clinical model to evaluate corticoid potency because the ability to perform within-patient comparisons of the treatment of bilateral lesions permits meaningful comparisons with a relatively small sample size. The results of bilateral comparisons in psoriasis agreed with those of the vasoconstrictor assay in 20 of 23 comparisons of active agents and in numerous comparisons of active corticosteroids with a placebo. Eczematous dermatoses do not lend themselves well to bilateral paired comparison studies and therefore require parallel treatment studies with relatively large sample sizes to produce statistically significant comparisons. PMID- 1428468 TI - Animal models for testing topical corticosteroid potency: a review and some suggested new approaches. AB - Animal models allow for testing the potency of topical corticosteroids by measuring their effects on induced conditions that are analogous to human skin disease. Animal models can examine the anti-inflammatory, anti-allergic, antiproliferative, and atrophogenic effects of topical corticosteroids. These test models as they are currently applied are relatively imprecise; however, innovations using newly available histologic, autoradiographic, and biochemical techniques have great potential for precisely quantitating the effects of corticosteroids in animal model systems. PMID- 1428469 TI - Human test models for bioequivalence of topical corticosteroids: a review. AB - It would be useful to have a safe, reliable, reproducible, and inexpensive human test model to determine the potency of topical corticosteroids and the bioequivalence of generic agents. Existing human test systems include erythema or inflammation induced by irritants or other stimuli, experimentally induced cutaneous disease-like states, and bioassays in patients with psoriasis. None of these systems is currently reliable enough to warrant general use. Among the shortcomings of existing test systems are the difficulty of producing a uniform, steroid-responsive test condition, the requirement to use occlusion in several of the systems, and the lack of agreement among the results of different tests. Despite these shortcomings, some of the tests may prove useful in comparing innovator and generic topical corticosteroids and in screening the potency of new agents. PMID- 1428470 TI - Smoking and lung cancer in China: combined analysis of eight case-control studies. AB - Smoking is well established as a principal risk factor for lung cancer. The risk of lung cancer is about ten times higher in smokers in Western countries. In China, a number of epidemiological studies have investigated the association between lung cancer and smoking and in the present paper, a combined analysis of eight such case-control studies is described. The summary odds ratio (OR), calculated by the Mantel-Haenszel method, and attributable risk (AR) of lung cancer associated with smoking were calculated from the combined data which were obtained from a literature review. The eight case-control studies were conducted in Beijing, Shanghai, Shenyang, Nanjing, Harbin, Zhengzhou, Taiyuan, and Nanchang, yielding a total of 4081 lung cancer cases and 4338 controls. The summary OR of lung cancer associated with smoking was 2.17 (95% CI (confidence interval): 1.98-2.39). The OR were 3.09 (95% CI: 2.61-3.66) for males and 2.30 (95% CI: 1.96-2.69) for females. The AR were 38.2% for both sexes, 56.7% for males and 25.5% for females. Risks of 1.00, 1.03, 2.04, and 3.33 showed a dose response relationship between lung cancer and number of cigarettes smoked per day. There were also significant dose-response relationships of lung cancer with duration of smoking (OR = 1.00, 1.02, 2.66), and age at start of smoking (OR = 1.00, 3.30, 2.36, 1.18). The OR and AR of lung cancer associated with smoking in China were much lower than those reported in Western countries and the possible reasons for this are discussed. PMID- 1428471 TI - Occupational and environmental hazards associated with lung cancer. AB - In a hospital-based case-control study 194 lung cancer cases, 194 hospital controls, and 194 population controls were interviewed for their smoking, occupational, and residential history by trained interviewers, using a standardized questionnaire. In order to include many different environmental exposures, case ascertainment took place in seven different hospitals with catchment areas ranging from rural to highly industrialized. Lung cancer risk strongly increases with cumulative cigarette dose, reaching an odds ratio (OR) of 16.19 (95% confidence limits (CL): 5.10, 51.33) for male smokers of more than 40 pack-years and an OR of 19.99 (95% CL: 4.98, 80.24) for female smokers of more than 20 pack-years. For the quantification of occupational exposure to known carcinogens of the lung a novel approach was developed which accumulates exposure information obtained by supplemental questionnaires through an automatic procedure. The OR for the highest exposure group in males was 2.7 (95% CL: 1.23, 5.78). Significantly increased risks were observed in the metal industry, particularly in smelter and foundry workers (OR 4.8, 95% CL: 1.15, 20.16) and in turners (OR 2.2, 95% CL: 1.05, 4.75). In the construction industry the risks were particularly high in road construction workers (OR 3.7, 95% CL: 1.06, 13.20) and in unskilled construction workers (OR 2.7, 95% CL: 1.24, 5.76). The risks in these occupational groups increased with duration and with latency. Quantification of air pollution was done on a county basis by time period. An index based on emission data for sulphur dioxide was compared to a semiquantitative index, which included additional information on ambient air pollution. After adjustment for smoking and occupational exposures an OR of 1.01 (95% CL: 0.53, 1.91) for an emission index and of 1.16 (95% CL: 0.64, 2.13) for a semiquantitative index was obtained. PMID- 1428472 TI - Relationship of blood prolactin levels and the risk of subsequent breast cancer. AB - Between 1968 and 1976 a total of 5162 women volunteers were enrolled into a prospective study conducted on the Island of Guernsey. Up to February 1990 145 women subsequently developed breast cancer. Blood samples were taken at the time of enrollment and prolactin levels were known for 85% of the volunteers. In calculating the relationship between blood prolactin levels and subsequent breast cancer risk, women were excluded if they had a hysterectomy or an oophorectomy or had cancer at any site before enrollment. The final analysis was based on 2596 premenopausal and 1180 naturally postmenopausal women and, of these respectively, there were 71 and 40 volunteers who subsequently developed breast cancer. The total follow-up for these two groups was 49,941 and 22,360 woman-years, respectively. In assessing the relationship between blood prolactin levels and risk of subsequent breast cancer the cohort was divided into quintiles according to prolactin concentration and relative risks (RR) were estimated. In calculating these values possible confounding by age at entry, age at menarche, parity, age at first birth, years since menopause, body build, history of benign breast disease and family history of breast cancer were taken into consideration. There was no significant relation between risk of breast cancer and prolactin in either pre- or postmenopausal women. Hence prolactin appears not to be an important determinant of breast cancer risk. PMID- 1428473 TI - Misclassification bias related to definition of menopausal status in case-control studies of breast cancer. AB - It is often assumed, but has not been consistently observed, that some characteristics of reproductive history are specifically related to breast cancer of pre- or postmenopausal onset. To determine whether inconsistent reports may be due to differences in definition of menopause, we computed the relative odds (RO) of breast cancer for nulliparity, age at first live birth, family history of breast cancer and prior history of benign breast disease, separately in pre- and postmenopausal women, using seven different definitions of menopause. Results show that (i) relative odds of breast cancer and their confidence intervals may vary according to definitions of menopause; (ii) age-based definitions of menopause are associated with moderate differential misclassification bias between cases and controls; (iii) nulliparity, late age at first birth and family history of breast cancer seem to be specific risk factors for pre- but not postmenopausal breast cancer when cutoff for menopausal status is 10 years or more after last menses; and (iv) when information on menstrual history is not available, 50 years of age may be the best proxy for all menses-based definitions of menopause. We conclude that inconsistent findings on the effect of menopausal status in the association of breast cancer with some reproductive factors are partly due to statistical imprecision and differential misclassification bias associated with different age-based or menses-based definitions of menopause. Researchers should either test whether their conclusions hold using several definitions of menopause or give a biological rationale for the choice of a given definition of menopause. PMID- 1428474 TI - Skinfold thickness and cardiovascular risk factors in American and Japanese telephone company executives. AB - Data from a cross-sectional study of cardiovascular disease risk factors in 962 US and 827 Japanese male telephone company executives were used to determine the associations of skinfold thickness measurements (abdominal, subscapular, triceps, ulnar) with blood pressure, blood glucose, serum cholesterol, and serum triglycerides. These associations were assessed within each group of executives and were compared between the groups. Most skinfolds showed association with risk factors in univariate regression. After adjusting for age and body mass index, the abdominal skinfold continued to be significantly associated with blood pressure and triglycerides in both groups, while the subscapular skinfold showed associations only with triglycerides. After adjustment, the peripheral skinfolds showed no association with risk factors in the US men, however, in the Japanese men the ulnar skinfold continued to be associated with blood pressure. These findings suggest that abdominal and ulnar skinfold measurement may be useful in adjusting for the effect of obesity on coronary heart disease risk in epidemiological studies. PMID- 1428475 TI - Are race differences in the prevalence of hypertension explained by body mass and fat distribution? A survey in a biracial population. AB - Body mass and body fat distribution are important considerations in the study of hypertension. However, few studies have investigated the relationships with regards to race differences in elevated arterial pressure. A population-based sample of black and white adults was assessed by interview and physical measurement. The prevalence of hypertension (defined as 140/90 mmHg and/or medically treated) was disproportionately higher among blacks than whites. In addition, blacks had a higher prevalence of the more severe hypertension (160/95 mmHg) and hypertension with higher prevalence at earlier ages than whites. Black females had a significantly higher distribution of body mass index (BMI) than white females, while no difference was found in the distributions of males. White males had a higher distribution of waist to hip ratio (WHR) than black males, while black females had the higher values compared to white females. The prevalence of hypertension increased with BMI and WHR. Blacks maintained higher rates of hypertension after controlling for BMI and WHR, however, the margin of difference diminished when BMI and WHR was considered together. The black-white difference in hypertension was not completely explained by BMI and WHR. In addition, the strength of the association of hypertension and body size was different for blacks and whites which suggests possible differences in the mechanisms regulating blood pressure. PMID- 1428477 TI - Serum sialic acid concentration predicts both coronary heart disease and stroke mortality: multivariate analysis including 54,385 men and women during 20.5 years follow-up. AB - To investigate the nature of the relationship between serum sialic acid concentration and cardiovascular mortality, the risks for coronary heart disease (CHD) and stroke were assessed separately in 26,693 men and 27,692 women followed during 20.5 years. Diastolic blood pressure, total cholesterol and body mass index were used as covariates in a person-year-based Poisson model. Relative risks for CHD mortality associated with the highest sialic acid quartile was 1.76 (95% confidence interval (CI): 1.58-1.96) in men and 1.94 (95% CI: 1.61-2.34) in women. Corresponding figures for stroke were 1.62 (95% CI: 1.26-2.09) and 1.68 (95% CI: 1.28-2.21) respectively. No significant patterns related to the age at entry was observed. For both genders, and both endpoints, diastolic blood pressure was associated with higher relative risk than sialic acid, and body mass index and serum total cholesterol were less predictive. Serum sialic acid concentration predicts both death from CHD and stroke in men and women independent of age. The biological foundation of this finding remains unclear. PMID- 1428476 TI - Blood pressure levels of Zambian rural adolescents and their relationship to age, sex, weight, height and three weight-for-height indices. AB - A study of blood pressure levels of 372 rural Zambian schoolchildren age 7-16 years showed that blood pressure increases with age. The association between age and blood pressure is decreased when growth is controlled for in the analysis. Girls tended to have either the same or slightly higher mean blood pressure levels at all ages than boys. The main determinants of blood pressure in the children were age, height and weight. Mean systolic blood pressure (SBP) values of the children were lower than those for Nigerian, American and worldwide adolescents of comparable age, whereas mean diastolic blood pressure values were similar to those of American and worldwide adolescents of comparable age. The associations between blood pressure and the three indices commonly used to measure relative obesity, i.e. weight-for-length, weight/height2 and weight/height,3 were only significant for weight-for-length after adjusting for height, suggesting that the other two indices may not be appropriate in studies focussed on children and should be applied with caution. The nonsignificant associations observed between blood pressure and the other two weight-for-height indices may be attributed to the almost nonexistence of obesity in this sample of children. PMID- 1428478 TI - Monitoring the incidence of myocardial infarctions: applications of capture-mark recapture technology. AB - It is critical to monitor the incidence of myocardial infarction. Typically, death certificates have been used as a proxy for incidence, however, these have been found to be crude as they lag behind changes in incidence. In the last decade several myocardial infarction registries have been established, however, these registries are still too limited in geographical spread to assess either national or global trends of heart attack. Here we suggest that employing an alternate approach, that of capture-mark-recapture, would be helpful to provide accurate monitoring both within and between countries. This method would complement existing registries by providing a simple and inexpensive means to provide accurate heart attack data across broad geographical areas and time. PMID- 1428479 TI - Risk factors for preterm and term low birthweight in Ahmedabad, India. AB - To identify and quantify risk factors for preterm and term low birthweight (LBW) we conducted a hospital-based case-control study, linked with a population survey in Ahmedabad, India. The case-control study of 673 term LBW, 644 preterm LBW cases and 1465 controls showed that low maternal weight, poor obstetric history, lack of antenatal care, clinical anaemia and hypertension were significant independent risk factors for both term and preterm LBW. Short interpregnancy interval was associated with an increased risk of preterm LBW birth while primiparous women had increased risk of term LBW. Muslim women were at a reduced risk of term LBW, but other socioeconomic factors did not remain significant after adjusting for these more proximate factors. Estimates of the prevalence of risk factors from the population survey was used to calculate attributable risk. This analysis suggested that a substantial proportion of term and preterm LBW births may be averted by improving maternal nutritional status, anaemia and antenatal care. PMID- 1428480 TI - A case-control study of paternal smoking and birth defects. AB - Although the influence of paternal smoking on birth defects is of great public interest, epidemiological evidence concerning this potential relationship is extremely limited. A stratified random sample of 29 hospitals in the Shanghai Municipality, China, was used to select 1012 birth defects cases and controls. Mothers of the cases and controls were interviewed in the hospitals from October 1986 to September 1987. A modest relationship between paternal smoking and overall birth defects in offspring was identified [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.01-1.45]. More markedly elevated risks were identified for anencephalus (OR = 2.1), spina bifida (OR = 1.9), pigmentary anomalies of the skin (OR = 3.3) and varus/valgus deformities of the feet (OR = 1.8). Our analysis also shows that paternal smoking is more likely to be associated with multiple rather than isolated malformations. A paternally mediated effect of smoking on birth defects is suggested and further studies are encouraged. PMID- 1428481 TI - Cigarette smoking in pregnancy and fetal growth. Does the type of tobacco play a role? AB - The effect of nicotine content of cigarettes on fetal growth was studied. From April 1985 to April 1987, 86% of all pregnant women in two well-defined geographical areas responded to a questionnaire on social conditions and lifestyle factors in pregnancy. After excluding multiple births and women who gave birth after elective caesarean section, 10,485 pregnant women were available for the study. Results showed that not only smoking, but also nicotine content in cigarettes was related to reduced fetal growth as measured by birthweight, birth length, and head circumference. The timing of smoking during pregnancy played a role. Smoking before pregnancy or smoking early in pregnancy was not related to fetal growth, nor were the partners' smoking habits. The study corroborates the hypothesis that smoking reduces fetal growth and points to nicotine as one of the potential causal factors. PMID- 1428482 TI - Perinatal 'TORCH' infections identified by serology: correlation with abnormalities in the children through 7 years of age. AB - A matched case-control methodology was used to assess the risk for a wide range of abnormalities in children associated with serological evidence for 'TORCH' infections in the mothers. Specimens were selected from the large bank of sera from the approximately 54,000 pregnant women who participated in the Collaborative Perinatal Project. There was no clear association between any of the antigens studied and any specific damage to the child. These 'negative' findings are consistent with the absence of frequent significant effects due to these agents in the second and third trimesters of pregnancy. PMID- 1428483 TI - Cigarette smoking and sick leave in an industrial population in Shanghai, China. AB - A study of cigarette smoking and sick leave was conducted at a large petrochemical complex in Shanghai, China in 1988. Among a random sample of 1856 men the smoking prevalence was 80% with the highest rate (84%) occurring in the age group 25-34 years. Only 53% of smokers and 76% of nonsmokers said they believed smoking was harmful to health and knowledge of which diseases were associated with smoking was poor. Retrospective data were also collected on sick leave in 1986 and 1987. In 1986 13% of men took sick leave and in 1987 12%; the mean duration of sick leave was 3 days per year. In 1986 the odds ratios (OR) for taking sick leave were 2.37 for heavy smokers and 1.45 for light smokers compared to unity for nonsmokers; the corresponding OR for 1987 were 1.70 and 1.28 for heavy and light smokers compared with nonsmokers. Smoking was positively associated with sick leave even after adjustment for age, consumption of alcohol and exposure to chemicals; OR = 1.56 (95% confidence interval (Cl): 1.06-2.31) in 1986 and OR = 1.32 (95% Cl: 0.90-1.95) in 1987. Demonstration of this association even in a young population with low sick leave rates illustrates yet again the adverse effects of smoking on health and the urgent need to reduce the very high prevalence of smoking in China. PMID- 1428484 TI - Smoking habits and attitudes of medical students towards smoking and antismoking campaigns in nine Asian countries. The Tobacco and Health Committee of the International Union Against Tuberculosis and Lung Diseases. AB - As part of a world survey of the habits, knowledge and attitudes of medical students regarding tobacco we report a study in 15 medical schools from nine Asian countries. Some 1646 first year and 1587 final year students were included, of whom 59% were male. The prevalence of daily smoking in males was 4% in first year and 11% in final year; of occasional smoking 18% and 24% respectively, both with considerable variations between countries. The rates were very low in women. Male exsmokers varied from 3% to 24% in different centres. Overall, 33% of smokers had made a serious attempt to quit; 44% expected to have succeeded within 5 years. Over 80% of non- or exsmokers, but only 60% of smokers, thought smoking was harmful to health. There was gross underestimation of tobacco's causal role in a number of important diseases, e.g. coronary artery disease, peripheral vascular disease, emphysema, bladder cancer and neonatal mortality. There were notable defects both in training and in motivation to counsel smoking patients. There was only partial knowledge of legislative and other measures to discourage smoking, e.g. only 44% of final year students (26% of smokers) thought increased taxation an important measure. In knowledge and attitudes there was little difference between the sexes, but in most aspects smokers had notably lower scores. PMID- 1428485 TI - The descriptive epidemiology of a sedentary lifestyle in adult Australians. AB - Regular exercise is important for the maintenance of good health, but many people do very little exercise. There are public health concerns about activating the sedentary and, from an epidemiological measurement perspective, there are advantages in assessing physical inactivity. Using pooled data from 17,053 participants in Australian population surveys, we identified 5078 people (29.7%) who could be classified as sedentary in their recreational exercise habits. Logistic regression analyses found the inactive to be more likely to be older, less well educated, and to have lower incomes. The main reasons given for not exercising were no time (33%), being physically unable (23%), and not wanting to exercise (13%): these were more likely to be reported by those who were older, and who had lower incomes; the only exception was that being 55 years or older was not associated with having less time. Women were more likely to report being physically unable to exercise. Lower income was associated with being physically unable, and with not wanting to exercise. Those with children, while wanting to exercise, were more likely to report having no time. The greatest health benefits will result from the sedentary becoming more active, and inexpensive and convenient activities such as walking need to be emphasized. PMID- 1428486 TI - Low sex ratios of births in areas at risk from air pollution from incinerators, as shown by geographical analysis and 3-dimensional mapping. AB - Previous research in environmental and occupational health has suggested that fluctuations in the sex ratios of births might provide a useful early warning to the possible health effects of toxins or other stresses in the environment. To examine further this hypothesis, we investigated the sex ratios of births in an area in central Scotland which contained two incineration plants. Analyses of the sex ratios, at various levels of geographical detail and using 3-dimensional mapping techniques, in the residential areas at risk from airborne pollution from these incinerators showed locations with statistically significant excesses of female births. PMID- 1428487 TI - Life table analysis of infant mortality and feto-infant mortality distributed on causes of death in Denmark 1983-1987. AB - The survival function of 263,322 singletons of the 1983-1987 Danish birth cohorts (262,159 liveborn and 1163 stillborn babies) with mortality distributed on functional groups of underlying causes of death is presented in two graphic forms on the basis of Kaplan-Meier estimates. About half of all first-day deaths in liveborn babies occurred during the first 4 hours. More than half of all first week deaths happened during the first day. More than half of all deaths from 31 weeks to 76 weeks after the first day of the last menstrual period (LMP) were either fetal deaths prior to the onset of labour unexplained by fetal factors or unexplained sudden infant death syndrome (SIDS) deaths. Graphic presentation of feto-infant mortality distributed on functional cause-of-death groups improved the expression of the relative contribution and timing of the different causes of deaths. Despite a high autopsy rate and a uniform coding practice the distribution on causes of deaths from register data should be interpreted with caution. Full use of the feto-infant approach is only achieved with data which include late abortions. Thus the feto-infant approach is of special interest in countries which have registers of live births and fetal deaths from week 22 of gestation or earlier. The integration of the life table approach and analysis of underlying causes of deaths should be further explored as a way of utilizing vital statistic databases for the evaluation of perinatal care. PMID- 1428488 TI - Region of birth and mortality of blacks in the United States. AB - Analysis of black American death rates by region of birth and region of residence showed that southern-born blacks had the highest mortality rates and western-born blacks the lowest mortality rates. Blacks born in the northeast, midwest, and outside the US had rates intermediate between southern and western-born black rates. Blacks born in one region and who died in another had age-specific and age adjusted mortality rates similar to their region of birth rather than their region of residence. PMID- 1428489 TI - The contribution of unemployment to socioeconomic health differences. AB - Unemployment and socioeconomic status (SES) are both related to mortality and health inequality or differences. The main purpose of this study is to assess the contribution of these factors to health status. Data have been analysed from over 500 employed and 500 unemployed men, 30-50 years old, in two highly industrialized areas of the Netherlands. Three scales of self-reported health were used: somatic complaints, depressive complaints and chronic diseases. Experimentally, four SES measures were tested separately: education, occupation and household income as single measures, and a composite score constructed from the weighted sum of these measures. Results show a clear independent influence of SES as well as unemployment on health differences, when indicated by occupation or education. Household income appears to influence the results, the implications of which are discussed. Including the longitudinal follow-up there are three measurements over time. These data were used to test a homogenizing hypothesis, questioning processes that might indicate the existence of one unemployed (under) class. This hypothesis was rejected. Finally the data indicated a small contribution of health selection processes on the labour market. PMID- 1428490 TI - Pets, allergy and respiratory symptoms in children. AB - The relationship between pet ownership and respiratory allergy and symptoms was investigated in a population of 3344 Dutch children of 6-12 years old. Pet ownership was defined by the presence of cats, dogs, birds and/or rodents in the home. The reported prevalence of respiratory allergy and symptoms was lower among children of current pet owners than among children of parents who owned no pets. When past pet ownership was taken into account, however, a different picture emerged. The lowest prevalence of respiratory allergy and symptoms was found in children of current pet owners who had no pets in the past. The next lowest prevalence was found in children of current pet owners who had had pets in the past also. The next highest prevalence was found in children who never had pets in their life. The highest prevalence of reported pet allergy, chronic cough, wheeze, attacks of shortness of breath with wheezing, and doctor-diagnosed asthma was found in children who had pets in the past but not anymore. Past cat ownership especially was associated with a high prevalence of pet allergy and doctor-diagnosed asthma. Almost 2% of the population reported to never have owned pets for health reasons, and more than 12% reported removing pets from the home for health reasons in the past. These results show that selective avoidance and removal of pets leads to distortions of cross-sectional associations between pet ownership and respiratory allergy and disease among children. PMID- 1428491 TI - Death certificate coding practices related to diabetes in European countries--the 'EURODIAB Subarea C' Study. AB - The objective of this study was to compare and analyse coding practices for diabetes mortality data in nine European countries (Belgium, Republic of Ireland, France, Germany, Malta, The Netherlands, Northern Ireland, Scotland and Switzerland). In each country, a sample of 200 coded death certificates, which mentioned diabetes, was randomly sampled. All death certificates were recoded at the WHO Collaborating Centre for the Classification of Diseases in the French language. The results show wide differences between national coding and central coding. Discrepancies in the underlying cause of death existed at the 3-digit coding level for 26% of all death certificates and for 44% at the 4-digit level. Coding in Northern Ireland and Malta was characterized by a marked tendency to choose diabetes less frequently. In contrast, in The Netherlands and, to a lesser extent, in the Republic of Ireland and France, diabetes was more frequently selected as the underlying cause of death. Most of the differences concerned the coding of an association involving diabetes and circulatory system diseases. In some countries, these coding differences influence the reported level of diabetes mortality. For Northern Ireland and Malta, the number of certificates with diabetes as the underlying cause of death was more than doubled after central recoding and for The Netherlands, in contrast, it was almost halved. To explain the differences a number of factors are considered: a lack of information from the International Classification of Diseases (ICD), on the application of the coding rules, between-country differences in cause of death certification practices, a divergence of opinion about the causal role of diabetes when it is associated with other conditions, a lack of homogeneity between countries in data collection procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428492 TI - Risk of developing insulin-dependent diabetes mellitus (IDDM) before 35 years of age: indications of climatological determinants for age at onset. AB - This study analyses data from two nationwide prospective diabetes registries now covering about 3400 cases from 19 million person-years of follow-up in the age group 0-34 years. The risk of developing insulin-dependent diabetes mellitus (IDDM) per 100,000 individuals before 15 years was 386 (95% confidence intervals (CI): 362-410) for boys and 391 (95% CI: 367-415) for girls and by 35 years 701 (95% CI: 671-731) for men and 562 (95% CI: 534-690) for women. The incidence rate showed a maximum for both boys and girls in early puberty. After pubertal years a sharp increase in the male to female incidence ratio of IDDM was notable. At 10 14 years it was 0.94, at 15-19 years 1.59 and at 20-24 years 2.08. A Cox regression model was used to analyse the effects on age at onset of sex, population density and climatological factors as measured by north-south area of residence and season at onset. The effect of sex was confirmed (P less than 0.001). A significant effect (P = 0.004) of season was shown when the four seasons were classified according to a four stage scale related to mean temperature. When dividing Sweden into 11 regions according to north-south gradient (Latitude 55 degrees, 56 degrees, 57 degrees, ..., 65 degrees) a significant effect (P = 0.038) was also found. However, no effects of population density or living near the coast versus in the interior were found. It is concluded that a large proportion of the young are at risk of developing this chronic disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428493 TI - Motor disability in children in three birth cohorts. AB - A systematic registration was carried out in 1985-1986 and 1989 in 14 French 'departments' in order to assess whether the prevalence rates of different components of motor disability (MD) in three different birth cohorts (1972, 1976 and 1981) had changed at a time when the preterm birth rate and neonatal mortality were decreasing and there was evidence of changing perinatal practice. A total of 1355 MD were registered amongst resident children born in 1972, 1976 and 1981 with a prevalence of 3.34 per 1000. The prevalence of the MD types due to different causes did not differ significantly amongst the three birth cohorts with the exception of an excess of hereditary and degenerative disease of the central nervous system (CNS) among children born in 1981. The prevalence of cerebral palsy (CP) remained stable in the three birth cohorts: it was 1.30, 1.06 and 1.08 per 1000 respectively, for children born in 1972, 1976 and 1981. The prevalence of pre- or perinatal-origin of other motor disabilities (OMD) and of CNS malformations did not differ amongst the three birth cohorts. The method of registration is discussed and the results are related to those of the French perinatal surveys performed in 1972, 1976 and 1981, which showed a decrease in preterm birthrate, an increase in perinatal care and a decrease in the mortality rate of high-risk infants. PMID- 1428494 TI - Prevalence of childhood disability in a southern Indian city: independent effect of small differences in social status. AB - A random sample of mothers living in two neighbourhoods of a southern Indian city were interviewed in order to determine the prevalence of serious disability in children 2-9 years old. These areas were selected because residents constitute either the lowest class or the next higher socioeconomic class (next-to-lowest class), with monthly incomes of US$ 10-15 and 32-42 respectively. A previously validated screening instrument was used with documented sensitivity of 100% and specificity of 95% when applied under similar conditions. Disability was found to be more common among children of the lowest class families (17.2%) when compared with the next-to-lowest class families (8.4%); with an odds ratio (OR) of 2.36 (95% confidence interval (CI): 1.08-3.64). Specific types of disability were examined and found to be consistently more prevalent in the lowest class. These results suggest that comparatively small differences in social status can be associated with important differences in health status. PMID- 1428495 TI - Conjunctival impression cytology with transfer as a field-applicable indicator of vitamin A status for mass screening. AB - The increasing importance of vitamin A deficiency in even its mild subclinical form underlines the need for a mass screening test. Clinical, biochemical and cytological methods of assessing vitamin A deficiency in a public health setting have been described and widely used. The cytological method shows promise because it enables early detection of vitamin A deficiency. However interpretation is problematic since histopathological changes are gradual with the progressive disappearance of goblet cells and appearance of enlarged epithelial cells. The reliability and validity of the impression cytology with transfer (ICT) test were assessed in order to produce a meaningful standard for this cytological method. The ICT test was performed in Senegal on 1451 children, in the course of two surveys conducted in 1989 and 1990 in rural areas. Reliability, estimated by Cohen's kappa test for evaluating intra-reader variability, and sensitivity were highest for the abnormal-normal classification (kappa = 0.91; 95% confidence interval (CI): 0.89-0.93; and sensitivity = 74%; 95% CI 66-82%). The ICT method is a cheap, noninvasive and easy test to perform in the field. This method is also reproducible and fairly sensitive according to the abnormal-normal classification. As illustrated by our proposed 50% cutoff of abnormal cytology calculated in relation to 5% of serum retinol values below 0.35 mumol/L criterion, ICT only requires a small sample for the assessment of the overall health of a community in contrast to xerophthalmia and blood vitamin A deficiency tests. PMID- 1428496 TI - The male predominance in the incidence of infectious diseases in children: a postulated explanation for disparities in the literature. AB - In children, a male predominance in the incidence of symptomatic disease has been reported for some infectious agents and not for others. Not only are the factors underlying these sex differences poorly understood, but it is also not clear why the differences are described only for selected infectious diseases. In this study of sex- and age-specific incidence of infectious diseases in children, a possible explanation for the inconsistencies in the literature was explored. The sex ratio in reported disease incidence in Israel during a period of about 20 years was examined for various viral and bacterial infections. In addition, an hypothetical mathematical model was developed which assumes increased susceptibility to infectious disease (such as in relative immune deficiency) in a proportion of males. In children aged under 4 years, a higher incidence among males was consistently observed for all diseases, and the sex ratio varied between 1.16 (95% confidence interval (CI): 1.13-1.18) for shigellosis to 1.98 (95% CI: 1.79-2.17) for viral meningitis. The highest ratios were associated with the diseases which tend to present asymptomatically most often, which is consistent with the predictions of the model. The male excess in symptomatic disease appears to be present for most infectious diseases and this should be taken into account in studies comparing observed disease incidence between groups with different sex ratios. The inconsistencies in reports on the excess male morbidity for infectious diseases may be due to variations in symptomatic to asymptomatic infection ratios. PMID- 1428497 TI - Asymptomatic subjects at HIV diagnosis have prolonged survival as AIDS patients. AB - The median AIDS survival for all AIDS patients was estimated as 11 months (95% confidence interval (Cl): 8-13 months). For the group of AIDS patients who were asymptomatic when HIV seropositivity was established, the median AIDS survival was 20 months (95% Cl: 13-23 months). For the group with symptomatic HIV infection or those who already had AIDS when HIV seropositivity was established, survival was estimated to 5 months (95% Cl: 1-15 months) and 4.5 months (95% Cl: 2-8 months), respectively. By using a Cox proportional hazard model it was found that being asymptomatic when HIV seropositivity was established or having Pneumocystis carinii pneumonia as the initial AIDS-related disease were associated with long AIDS survival. Being HIV infected by transfusion was associated with short survival. Long AIDS survival in the asymptomatic group may be explained by a positive selection of slow disease progressors. Differences in diagnostic routines may also cause systematic differences in the estimated AIDS survival. PMID- 1428498 TI - The prevalence and regional distribution of antibodies against Chlamydia pneumoniae (strain TWAR) in Finland in 1958. AB - The occurrence of nonavian 'ornithosis' was reported in Scandinavia at the end of the 1950s. In order to find out whether Chlamydia pneumoniae had been present in Finland, we examined the IgG antibody prevalence to C pneumoniae in samples representing the whole rural population of Finland in 1958. The total number of sera studied using micro-immunofluorescence was 2000. Trend-surface analysis was used to examine the regional patterns of antibody prevalence. C pneumoniae antibodies were present throughout the country. The mean antibody prevalence was 56% among adults and 27% among children. Thus the possible role of C pneumoniae in nonavian 'ornithosis' in Finland between 1958 and 1960 cannot be excluded. PMID- 1428499 TI - Risk factor dynamics, mortality and life expectancy differences between eastern and western Finland: the Finnish Cohorts of the Seven Countries Study. AB - Prior studies have not accounted for male mortality being higher in east than west Finland. Efforts to identify the mechanisms producing higher mortality in the east, due primarily to cardiovascular diseases (CVD), initially focused on a search for new risk factors. An alternate approach is to examine the assumptions of the analysis. This was investigated using a model which described (a) changes in risk factors over time, (b) dependency of risk factor effects on age, and (c) interactions and nonlinear effects of risk factors on mortality. The model was applied to 25-year follow-up data from cohorts of eastern (N = 823) and western (N = 888) Finnish men using pulse pressure, diastolic blood pressure, body mass index, total cholesterol, vital capacity index, cigarette smoking, and heart rate as risk factors. At age 40, men in the west had a life expectancy 2.4 years higher. Of the difference 29% (0.7 years) was associated with area differences in risk factor means, variances, and their change with age. The remainder, 1.7 years, was associated with age differences in the relation of risk factor interactions to CVD mortality. Possible reasons for these differences, such as joint elevation of several risk factors inducing rapid progression of atherogenesis, are discussed. No significant area differences were observed for mortality from either cancer or other causes. PMID- 1428500 TI - Oral contraceptive 'potencies' and deep venous thromboembolism. PMID- 1428501 TI - Increased accuracy in self-reporting on work histories following minor adaptations of the questionnaire. PMID- 1428502 TI - Problems in ecological studies. PMID- 1428503 TI - Stimuli for acquired resistance to Heligmosomoides polygyrus from intestinal tissue resident L3 and L4 larvae. AB - L3 and L4 stages of H.polygyrus were prevented from developing further and were probably killed within 24 h of treatment with ivermectin although total parasite burdens, particularly when treatment was given 4-6 days after infection, declined over a longer period lasting several days. Strong resistance to challenge infection was expressed by infected mice dosed with ivermectin during the tissue phase of larval development. Even immunizing infections as brief as 12-36 h (when only L3 larvae would have been present in the mucosa) elicited strong acquired immunity. When infections were terminated 4-6 days after infection, acquired resistance was 95-100%. The stronger resistance of mice exposed to both L3 and L4 stages was associated with the recognition of low molecular weight polypeptides in adult worm homogenate and there was a highly significant correlation between percentage protection and anti-L4/anti-adult worm serum IgG1 antibodies. PMID- 1428505 TI - The influence of weather and egg contamination on the development of third-stage larvae of Cooperia oncophora on pasture. AB - The influence of weather and egg contamination on the dynamics of herbage contamination with infective larave of Cooperia oncophora was investigated on artificially contaminated grass plots and in a grazing experiment with 24 first year grazing calves from May to October 1987 in Lower Saxony, Germany. On the experimental plots the larval translation was highest at the beginning of July and in the second part of September, following high mean weekly temperatures. Between July and September peak recovery of larvae from herbage occurred 4 weeks after contamination. A seasonal pattern of larval translation similar to that on the experimental plots could be demonstrated on the grazed pastures when the number of larvae per m2 of pasture had been adjusted to the previous egg output by means of a contamination index. The resulting 'relative larval density' is regarded as a good indicator for larval development on pasture. From July to September the larval population on pasture resulted mainly from the egg contamination 2-3 weeks earlier. The short persistence of the infective larvae on herbage was probably due to the frequent and heavy rainfall throughout the season, causing a passive washout of larvae into the soil. On single pastures the larval density started to increase within 1 week after the calves had first contact with these fields. The impact of the calves on the distribution of larvae is discussed. PMID- 1428504 TI - Hydrolysis of L-leucine methyl ester by Leishmania mexicana mexicana amastigote cysteine proteinases. AB - The main cysteine proteinases of the amastigote form of Leishmania mexicana mexicana were partially purified by gel filtration and ion exchange chromatography. The latter procedure resulted in the separation of some individual cysteine proteinases, as demonstrated by gelatin-sodium dodecyl sulphatepolyacrylamide gel electrophoresis. Fractions containing the partially purified proteinases rapidly hydrolysed L-leucine methyl ester to leucine. The activity towards this compound co-eluted with and resembled the parasite's cysteine proteinase activity. The results suggest that amastigotes of L.m.mexicana are susceptible to L-leucine methyl ester because this compound is rapidly hydrolysed by cysteine proteinases that occur in abundance in the megasomes of this stage. PMID- 1428506 TI - Analysis of the composition of samples of Babesia bovis and the influence of different environmental conditions on genetically distinct subpopulations. AB - A recombinant DNA probe specific for a tandemly repeated sequence located within the BoVA1 gene of Babesia bovis was used to analyse 10 independent samples of B. bovis. Twelve different alleles of the BoVA1 gene and flanking regions were identified in the 18 different subpopulations analysed. Most samples of B. bovis originally derived from single animals contained more than one genetically distinct subpopulation. However, only one population of parasites was identified in samples of the Ka line used in Australia from 1979 until 1990 as the live attenuated vaccine strain. In contrast, the replacement attenuated vaccine line, Ta, contained two genetically distinct subpopulations of parasites. Changes in the ratios of subpopulations of parasites were identified during attenuation and under different culture conditions. Batch-to-batch variation in the composition of doses of the live attenuated vaccine may lead to differences in efficacy and in severity of the infection associated with vaccination. PMID- 1428508 TI - A preliminary study of the effect of microclimate on third-stage larvae of Haemonchus contortus and Haemonchus placei on irrigated pasture. AB - Assessments were made on the influence of several microclimatic variables on the availability of third-stage larvae of Haemonchus contortus and Haemonchus placei on four strata of irrigated Kikuyu pasture. Three replicates of these pasture samples were collected on 18 sample days over 12 months and the log10 mean counts of the larvae recovered were analysed by a step-wise regression model. Predictors for the log counts of the four strata for the two nematode species included relative humidity, illumination, air temperature and windspeed. The effect of air temperature on larvae of both Haemonchus species was similar; as air temperature increased, the number of larvae on pasture increased. The inverse was true for windspeed; as windspeed increased larval counts decreased. For H. contortus, relative humidity increased as the number of larvae increased on all strata except upper herbage. The R2 values ranged from 0.11 to 0.21 for H. contortus and from 0.04 to 0.12 for H. placei. Under the conditions of this study, only 21% of the effect on H. contortus and 12% on H. placei third-stage larvae on pasture can be explained by microclimatic conditions. PMID- 1428507 TI - The influence of Mesocestoides corti on subsequent Angiostrongylus cantonensis infections in mice. AB - The influence of Mesocestoides corti on subsequent Angiostrongylus cantonensis infection in mice (C57BL/6 and BALB/c) was assessed. Both strains of mice infected with M. corti demonstrated a peak blood eosinophilia at around 3 weeks post-infection (p.i.). C57BL/6 and BALB/c mice primarily infected with M. corti were given A. cantonensis infection 18 days later, but pre-existing M. corti infection did not affect the recovery of intracranial worms of A. cantonensis at day 21 p.i. BALB/c mice with mixed parasite infections showed low morbidity and mortality as compared with mice singly infected with A. cantonensis and some mice demonstrated a pulmonary migration of intracranial worms. In C57BL/6 mice, intracranial worms were killed and thus all mice survived. C57BL/6 mice with mixed parasite infections failed to resist A. cantonensis reinfection. The blastogenic responses of spleen cells against A. cantonensis antigen were lower in BALB/c than in C57BL/6 mice and mixed parasite infections also resulted in less blastogenic responses against both concanavalin A and A. cantonensis antigen than monoinfection. The recovery of M. corti biomass was significantly higher in mice with mixed parasite infections than mice with monoinfection with M. corti. These data suggest a distinct difference in response to A. cantonensis infection between C57BL/6 and BALB/c mice, and the induction of immunosuppression in both mouse strains following M. corti infection. Blood eosinophilia provoked by M. corti infection is not directly associated with the killing of worms in subsequent A. cantonensis infection. PMID- 1428509 TI - Determinants of host-specificity in parasites of freshwater fishes. AB - Factors responsible for interspecific variability in host-specificity were investigated within 15 genera (including 176 species) of metazoan parasites found in Canadian freshwater fish. For each species in a genus, the parasite's number of known hosts was determined from published host-parasite records. The effects of the total number and mean size of potential hosts (i.e. all fish species belonging to the family or families that include a parasite's known hosts) on number of hosts of congeneric species were evaluated using multiple regressions. Since parasite species that have been recorded often tend to have greater numbers of known hosts than do seldom-recorded parasites, it was necessary to control for the confounding effect of study intensity. In all parasite genera, whether from highly specific taxa such as monogeneans or from less host-specific ones, there was a positive relationship between the number of potential hosts and the number of known hosts. However, no consistent relationships were observed between the mean size of potential hosts and number of known hosts. These results suggest that the availability of suitable host species may have been a key factor limiting the colonization of new hosts by fish parasites. PMID- 1428510 TI - Nymphal Ixodes dammini: models of the temporal abundance patterns. AB - A difference equation model was developed to explore the sensitivity of the temporal pattern of relative abundance of active, host-seeking nymphal Ixodes dammini. Inputs to the model were the temporal patterns of recruitment of nymphs into the active class, mortality and successful acquisition of hosts by the ticks. Input parameters were varied both in the temporal pattern (shape) and in the cumulative level (summed over the period of activity). The output of the models, the temporal abundance pattern, was examined for (1) overall shape and (2) the timing of the peak abundance of host-seeking nymphs. The shape of the temporal pattern of nymphal abundance was not sensitive to changes in the shape of the functions used as input for host-finding. The time of peak abundance of nymphs is slightly sensitive to changes in the overall level of host-finding and mortality. When more ticks are removed from the active class (host-finding or mortality increasing), the time of the peak abundance of the nymphs shifts earlier. However, this shift is small compared to variation in field data. The general shape of the activity pattern was sensitive to changes in the temporal pattern of recruitment. A left-skewed distribution produced output which most resembles field data. The temporal pattern of nymphs entering the active class is important, and is an area which needs further empirical work. PMID- 1428511 TI - Immunization against geographical isolates of Trichinella spiralis in mice. AB - Partially purified antigen preparations from six isolates of Trichinella spiralis were used to immunize mice. Immunogenicity of the antigens was assessed in terms of antibody and lymphocyte responses and ability to stimulate protective immunity against challenge. Isolate antigens showed considerable cross-reactivity, and all elicited protective responses. Two major patterns of immunizing ability could be distinguished: (a) isolates that immunized well against heterologous challenge and elicited good immunity in London isolate-immunized mice (C-76 and Laso), and (b) isolates that immunized poorly against heterologous challenge and were least effective in London isolate-immunized mice (GM-1 and Mad-83). The immunogenicity of one isolate (C-76) was markedly greater than the others, inducing rapid loss in unvaccinated mice, almost complete protection in London isolate-immunized mice, and immunity in London isolate-challenged mice equivalent to the homologous antigen. These variations in immunogenicity, cross-reactivity and immunizing ability are discussed in terms of constraints that may operate against the development and use of vaccines against parasites that are widely distributed geographically. PMID- 1428512 TI - A model for nematodiasis in New Zealand lambs. AB - A strategic model is described for the epidemiology of mixed nematode infections in New Zealand lambs. The model successfully reproduces known patterns of parasite epidemiology and production loss in lambs under currently implemented control strategies. The variation in model output during sensitivity analysis was within acceptable limits defined by field data. Model output was most sensitive to variation in parameters affecting survival and migration of the free-living stages and host resistance to infection, suggesting that these factors are most influential in regulating parasite populations. It is intended to use the model to focus research on key aspects of nematode epidemiology and control and, following the incorporation of appropriate genetic mechanisms, anthelmintic resistance. PMID- 1428513 TI - Predisposition to reinfection by intestinal helminths after chemotherapy in south Thailand. AB - Rates of reinfection by the intestinal helminths hookworm, Ascaris lumbricoides and Trichuris trichiura after chemotherapy were studied in two villages in Phang Nga Province, southern Thailand. It was found that intensity of infection levels attained after reinfection correlated positively with pretreatment intensities of infection for all parasites. This implies that certain persons in the community are predisposed to receiving high numbers of worms, due either to environmental or personal risk factors. Therefore, it would be advantageous to identify such persons and treat them preferentially. Targeted chemotherapy, however, should be combined with efforts to identify the risk factors that vary within the community and direct educational efforts or environmental intervention towards the section of the community most affected by the parasites. PMID- 1428514 TI - Coccidia of the domestic goat (Capra hircus) in Saudi Arabia. AB - Faeces of 228 domestic goats (Capra hircus) from the central region of Saudi Arabia were examined for the presence of coccidian oocysts. Ten species of coccidia were identified and described. A total of 90.3% of the specimens were positive, most of them contained 100-1000 oocysts per g of faecal sample. Kids less than 1 year old had higher oocyst counts than goatlings or adult goats. Mixed infections with three to five species were found in 69.7% of the specimens and six to eight species were found in 10.1%. Eimeria arloingi and E. hirci were most prevalent. E. alijevi, E. ninakohlyakimovae, E. caprina, E. christenseni and E. apsheronica were less common. E. jolchijevi, E. caprovina and E. punctata were relatively rare. PMID- 1428515 TI - Intestinal contractions and migration behaviour in Hymenolepis diminuta. AB - The aim of this study was to determine if intestinal contractions were important in the migration behaviour of the rat tapeworm Hymenolepis diminuta. The objectives were to investigate the intestinal motility responses of the host to a meal which initiates worm migration, and the worms' responses to an artificial peristaltic contraction. A 1 g glucose meal elicited a significant orad migration by H. diminuta in the small intestine of the rat host when compared to water-fed controls (P less than 0.05). The glucose meal also significantly increased the transit rate, and thus, frequency of intestinal contractions in the small intestine of the rat, when compared to water-fed controls (P less than 0.05). Application of a circumintestinal ligature (6.3 g) (simulating an intestinal peristaltic contraction) resulted in significant worm migration when the ligature was applied in regions containing the worm's strobila as compared to controls where loose ligatures were tied in regions containing the strobila, or to controls where tight ligatures were tied ahead of the worm's strobila. These results suggest that H. diminuta migrates in an orad direction in response to the mechanical pressure produced by intestinal contractions induced by host feeding. It is concluded that contractions of the small intestine are an important cue in the migration behaviour of this cestode. PMID- 1428516 TI - Maintenance of Sparganum proliferum in vitro and in experimental animals. AB - Successful in vitro and in vivo maintenance of Sparganum proliferum is described for the first time. Various experimental animals including hamsters, mice and a monkey were evaluated. Albino mice inoculated either subcutaneously or intraperitoneally allowed the survival and multiplication of larvae for as long as 72 weeks. Intensity of infection was proportional to the length of exposure; however, the number of larvae collected from inoculated animals varied widely when infection lasted for 6 or more months. Inoculation of single larval segments appears as effective as that of complete larvae. Although Minimal Essential Medium allowed the survival of S. proliferum for as long as 14 weeks, growth was observed only during the first 4 weeks of culturing. Despite initial in vitro growth of larvae, neither differentiation into a more developed stage nor multiplication was obtained. PMID- 1428517 TI - A case of ileus caused by a spiruroid nematode. AB - A 34-year-old male living in Aichi Prefecture, Japan, complained of lower abdominal pain. Ileus was suspected based on his clinical history and symptoms, and a laparotomy was performed. Four sections of a nematode were found in a large eosinophilic granuloma in the intestinal wall, and were identified as the larva of a spiruroid nematode. This is the third reported case of a spiruroid nematode infection found in the ileum. PMID- 1428518 TI - Human Chang liver cells show large surface openings and endocytic channels that resemble those in the amoeba. AB - Cytolysis of host cells by pathogenic Entamoeba histolytica can be blocked by specific lysozyme inhibitions and is recently reported to be enhanced by phosphoinositide (PI) signal transduction activation. However the mechanistic relationship between PI second messenger targets and massive lysosomal secretion needed to achieve rapid host cell lysis is unclear. We have previously shown that intracellular alkalinization associated with activated PI hydrolysis produces a massive endocytosis of huge proportions which would force a corresponding exocytosis for the maintenance of overall cell dimensions. These endosomes are processed by primary lysosomes. Apparently then, the massive exocytosis secretory pathway could provide the means for the ejection of lysozymes over target cells. We show here using human Chang liver cells that intracellular alkalinization produced large surface pittings similar to those seen in pathogenic E. histolytica in a rounded state. The SEM profile is correlated with the TEM profile of large endosomes containing extracellular debris and endosomes associated with primary lysosomal vesicles, which could support the notion that some of the pittings seen in the rounded Chang cells and the pathogenic amoebae are exit portals for endosome-lysosomes. PMID- 1428519 TI - Babesia bovis, Babesia bigemina, Babesia canis, Babesia microti and Babesia rodhaini: comparison of ribosomal RNA gene organization. AB - The three ribosomal DNA (rDNA) units have been cloned from an Australian isolate of Babesia bigemina. The organization of the units is very similar to that reported for a Mexican isolate of B. bigemina. In Babesia canis four rDNA units have been identified. Both Babesia rodhaini and Babesia microti contain two different rDNA units. A small number of different rDNA units appears to be a common feature of this group of Protozoa. Restriction enzyme analysis of the rDNA units form these species and B. bovis suggests that the genus Babesia as currently defined does indeed include two distinct groups of organisms namely, B. bovis, B. bigemina and B. canis and B. rodhaini and B. microti. PMID- 1428520 TI - Crystal structure of valinomycin-monohydrate cage complexes crystallized from dioxane. AB - Valinomycin, cyclo-[(L-Val-D-Hyv-D-Val-L-Lac)3-], was crystallized from aqueous dioxane solvent as a monohydrate complex in which water molecules were found within the ion-binding cavity of the ionophore: monoclinic P2(1), a = 14.377 (3), b = 41.554 (14), c = 14.080 (3) A, beta = 118.27 (2) degrees, Z = 4. There are two non-equivalent valinomycin-water complexes and three dioxane molecules in the asymmetric unit. The ionophore molecules adopt two similar but non-identical, octahedral, bracelet, cage conformations that are a consequence of two distinct ways in which the complexed water molecules can deform the normal octahedral coordinate geometry of the metal binding site. In the first complex the water molecule forms hydrogen donor bonds to the carbonyl oxygens of two L-valine residues on one facial side of the cavity, while in the second complex the water molecule is trigonal-planar coordinate and binds to two L-valine residues on one entrant face of the cavity plus a third D-valine residue from the opposite side of the cavity. PMID- 1428521 TI - Simultaneous use of 1-hydroxybenzotriazole and copper(II) chloride as additives for racemization-free and efficient peptide synthesis by the carbodiimide method. AB - In the carbodiimide mediated coupling of Z-Gly-L-Val-OH with H-L-Val-OMe in DMF, the simultaneous use of HOBt and copper(II) chloride as additives was found to give the desired peptide in a high yield without racemization. In the presence of HOBt, reducing the amount of copper(II) chloride produced a higher yield. Besides improving the coupling efficiency as compared with the case using copper(II) chloride alone as an additive, the present procedure offered another advantage for racemization suppression. Thus, even for the couplings where a low level of racemization was observed in the presence of copper(II) chloride, the simultaneous addition of HOBt and copper(II) chloride resulted in the elimination of racemization. The effectiveness of this new procedure using the two carbodiimide additives in the synthesis of biologically active peptides was assessed by the preparation of a protected Leu-enkephalin. In the 4 + 1 segment condensation using HOBt and copper(II) chloride simultaneously as additives, no racemization was detected and the yield was high enough. The elimination of racemization and improvement of coupling efficiency produced by the present procedure can be attributable to a reduced tendency for the activated forms of the carboxyl component to form a 5(4H)-oxazolone by the action of HOBt, and to the prevention of racemization by copper(II) chloride of the small amount of the oxazolone formed which is not eliminated by the action of HOBt alone. PMID- 1428522 TI - Dermorphin tetra- and heptapeptide analogues containing a [3,4] amide bond replacement by a carbon-carbon double and single bond. AB - Seven dermorphin hepta- and tetrapeptide analogues containing [3,4] amide bond replacement by a carbon-carbon double and single bond were prepared. 1H NMR studies of the pseudoheptapeptide in DMSO indicate the presence of extended conformations with stacking of the side chains in the N-terminal part and an inverse gamma-turn around Ser7 in the conformational equilibrium. The binding data show that the affinity of the analogues for the mu-receptor is only slightly diminished in the D-Ala2 series and is more affected in the D-Arg2 series. Since the Gly4NH is not present in these compounds we conclude that this NH is not required to stabilize the bioactive conformation nor is it directly involved in binding to the receptor. PMID- 1428523 TI - Structure activity studies of tryptophan30 modified analogs of Ac-CCK-7. AB - Cholecystokinin represents a family of gut hormones which among other activities, have been proposed to participate in satiety signaling. Ac-CCK-7[Ac-Tyr(SO3H)-Met Gly-Trp30-Met-Asp-Phe-NH2 (2)] possesses the full spectrum of activity and potency of the intact hormone; thus analogs of 2 may be useful as anorectic agents. A series of derivatives has been prepared in which the tryptophan indole moiety of 2 has been modified. The new compounds were assayed in CCK binding assays using homogenated rat pancreatic membranes and bovine striatum as a source of CCK-A and CCK-B receptors respectively and in vivo in rats for anorectic activity. Although previous studies have concluded that the indole ring of Trp30 is a critical pharmacophore for the interaction of CCK with both its A and B type receptors, we find 2-Nal30-Ac-CCK-7 (20) to be nearly equipotent to 2 in both CCK binding and as an anorectic agent sensitive to blockade by the Merck CCK-A receptor antagonist MK-329. The extreme structural sensitivity of this anorectic activity is illustrated by the 1-naphthylalanine30 (19) and (benzo[b]thien-2 yl)alanine30 (21) analogs which are 30 and 100 times less potent than 2 respectively. Other mono- and bicyclic Trp30 replacements, including substituted phenylalanines, 3-quinolinylalanine, and 2-(5,6,7,8-tetrahydro)naphthylalanine, gave inactive compounds. PMID- 1428524 TI - Alkylation of histidine with maleimido-compounds. AB - Introduction of the maleimide function via a spacer into histidine-containing peptides was found to produce ring closure by nucleophilic addition of the Nim imino function of the histidine side-chain to the activated double bond of the maleimide. As an intramolecular cyclization reaction it proceeds at remarkably higher rates than the bimolecular alkylation of histidine derivatives with N ethyl-maleimide. Correspondingly, in the case of the histidine-peptides examined only mixtures of the cyclic isomeric compounds were isolated and structurally characterized by 1H-NMR analysis. As expected, prevention of this reaction in histidine-containing maleoyl-peptides can be achieved by Nim-protection of the imidazole group. However, upon removal of this protection, the reaction takes place again, thus remarkably hampering the usefulness of the maleimide/thiol addition principle in conjugate chemistry for peptides. On the other hand this reaction could represent an interesting new approach for the design of cyclic peptidomimetic analogs. PMID- 1428525 TI - Geometry of proline-containing alpha-helices in proteins. AB - Crystal structure analysis of proline-containing alpha-helices in proteins has been carried out. High resolution crystal structures were selected from the Protein Data Bank. Apart from the standard internal parameters, some parameters which are specifically related to the bend in the helix due to proline have been developed and analyzed. Finally the position and nature of these helices and their interactions with the rest of the protein have been analyzed. PMID- 1428526 TI - Degradation of aspartic acid and asparagine residues in human growth hormone releasing factor. AB - Products of the degradation of human growth hormone-releasing factor (GRF) in aqueous solutions (15-200 microM) have been isolated and fully characterized. The cleavage product, GRF(4-44)-NH2, and the isomerization product, [beta-Asp3]GRF(1 44)-NH2, from the degradation of GRF(1-44)-NH2 in acidic solution and the corresponding products, GRF(4-29)-NH2 and [beta-Asp3]GRF(1-29)-NH2, from the degradation of GRF(1-29)-NH2 have been isolated and characterized. The products, [beta-Asp8]GRF(1-44)-NH2 and [Asp8]GRF(1-44)-NH2, from the deamidation of GRF(1 44)-NH2 at pH 8.0 and the corresponding products, [beta-Asp8]GRF(1-29)-NH2 and [Asp8]GRF(1-29)-NH2, from the deamidation of GRF(1-29)-NH2 have been isolated and characterized. All the degradation products of GRF(1-44)-NH2 and GRF(1-29)-NH2 were evaluated for biological activity and found to have much lower in vitro potencies than the parent peptides. Degradation occurs at Asp3 and Asn8 and the kinetics of these various transformations versus pH and temperature have been studied. GRF is most stable at pH 4-5. At pH below the pKa of the Asp3 side-chain (pH less than 4), cleavage at Asp3-Ala4 is the major route of degradation. For pH greater than 4, isomerization of Asp3 to beta-Asp3 (iso-Asp3) predominates. The rates of cleavage and isomerization are simple first order and vary with pH, independent of buffer concentration, such that the protonated (COOH) form of Asp3 undergoes cleavage while the ionized (COO-) form isomerizes. The more rapid deamidation of Asn8 to generate beta-Asp8 and Asp8 in about a 4:1 ratio, presumably via a cyclic imide intermediate, occurs at pH greater than or equal to 5 and is general base-catalyzed. Evidence was also obtained for direct hydrolysis of protonated Asn8 in GRF(1-29)-NH2 at pH less than or equal to 2 to give exclusively [Asp8]GRF(1-29)-NH2. The deamidation of Asn8 in GRF(1-29)-NH2 at pH 8.0, 22-55 degrees C, is relatively insensitive to temperature for T less than 37 degrees C, possibly due to conformational constraints. Asp25 and Asn35 are sterically, conformationally, or otherwise hindered with respect to these changes as no degradation at these sites was observed under the conditions employed. PMID- 1428527 TI - Phosphoryl group participation leads to peptide formation from N-phosphorylamino acids. AB - N-phosphorylated amino acids without a side chain functional group can transfer themselves into peptides after prolonged standing in solvents at warm temperatures. Seven N-phosphorylpeptides and free peptides were isolated and their structures determined. The phosphoryl group participation is the key to the peptide formation. An intramolecular mixed carboxylic-phosphoric anhydride intermediate was proposed for this type of reaction which might provide a clue to the function of the phosphoryl group in the phosphorylated enzymes and in the prebiotic synthesis of protein. PMID- 1428528 TI - New convenient synthesis of immunostimulating peptides containing meso diaminopimelic acid. Syntheses of FK-565 and FK-156. AB - A new improved synthesis of two immunostimulating peptides: FK-156 (D-lactyl alanyl-gamma-D-glutamyl-(L)-meso-2,6-diaminopimelyl-(L)- glycine) and FK-565 (heptanoyl-gamma-D-glutamyl-(L)-meso-2,6-diaminopimelyl-(L)- D-alanine) is described. A proper differentiation between the two chiral amino acid moieties of diaminopimelic acid was accomplished by selective enzymatic hydrolysis of one methyl ester group of the L-centre of Z2-meso-A2pm(OMe)2 (2). Utilization of a commercially available protease and diester 2 as an enzyme substrate made possible the relatively simple synthesis of a key intermediate 4 and considerably simplified the final deprotection steps. Aminolysis of the N-carboxyanhydride (4) with D-AlaONBzl or GlyONBzl was chosen to obtain the appropriate dipeptides with one free amino group as convenient intermediates for further peptide synthesis. The BOP reagent, used for peptide bond formation, secured good yields and high chemical and chiral purity of the peptides. A modification of alanine deamination procedure leading to a significant increase of D-Lac(OAc) yield is presented. PMID- 1428530 TI - An equine growth hormone molecular species lacking the 76-92 peptidic fragment. AB - A new eGH molecular species was isolated and purified by reverse phase HPLC. SDS polyacrylamide gel electrophoresis, amino acid composition, and C- and N-terminal determinations support a primary structure identical to that described by Zakin et al. (1976), except for the lack of the 76-92 peptidic fragment and the maintaining of 30% of its biological activity. PMID- 1428529 TI - Binding and spectroscopic properties of ostrich neurophysins. Probing the role of residue 35 at the monomer-monomer interface. AB - Binding and spectroscopic properties of ostrich neurophysins were examined with emphasis on the behavior of Tyr-35, a residue that provides a potential probe of the monomer-monomer interface and of allosteric interrelationships between this region and the binding site. Mesotocin-associated ostrich neurophysin was found to bind oxytocin and related peptides with affinities comparable to the mammalian proteins, but induced a significantly different optical activity in bound peptides than the mammalian proteins. Gel-filtration studies indicated higher dimerization constants for the ostrich neurophysins than for the bovine neurophysins. Consistent with this, Tyr-35 was found to be largely buried, as monitored by tyrosine titration and lack of reactivity towards tetranitromethane under non-denaturing conditions. Reaction of Tyr-35 of the mesotocin-associated protein with tetranitromethane under denaturing conditions, followed by refolding, allowed isolation of an active product with an altered interface region as partially evidenced by its titration properties and consistent with its markedly altered CD spectrum. Comparison of the CD spectra of the modified and native proteins and analysis of pH effects indicated the contribution of Tyr-35 to an unusual 237 nm band in the mesotocin-associated protein. Small shifts in the 350 nm CD band of nitrated Tyr-35 on binding peptide and apparent effects of nitration on the induced optical activity in bound peptide provided evidence of at least weak structural communication between Tyr-35 and the binding site. However, no significant effect of nitration on binding affinity was observed, suggesting that, in the mesotocin-associated protein, the region around residue 35 is not a stringent modulator of the thermodynamic behavior of the binding site. PMID- 1428531 TI - Apparent specific volumes of some dipeptides (containing L-valine and L-leucine in aqueous alkylurea solutions). AB - The apparent molal volumes of nine dipeptides containing glycine, L-valine, and L leucine have been determined in methyl, N,N'-dimethyl and ethylurea solutions from precise density measurements. Limiting partial molal volumes. V2(0), at various solute concentrations have also been calculated. The experimental values of V2(0) in water agree reasonably well with those calculated as the sum of V2(0) of both acids after accounting for the electrostrictive effect and loss of water. There is no correlation between the values of V2(0) of individual dipeptides in alkylureas which means that the intrinsic volume and the electrostrictive effect make the largest contribution to V2(0). The contribution from other effects is within the limit of experimental error. The volumes of transfer from water to alkylurea solutions are all positive and reflect by and large the electrostrictive effect. PMID- 1428533 TI - Pepsin as a catalyst of peptide synthesis. Enzyme co-precipitation with emerging peptide products. AB - Pepsin successfully catalyzed the synthesis of several peptide derivatives from N protected di- or tripeptides and amino acid or peptide esters or p-nitroanilides in dimethylformamide-water solutions at pH 4.6. An optimal substrates:pepsin ratio depended on the structure of starting peptides, especially their fit to the substrate binding sites of the enzyme. For hexapeptide Z-Ala-Ala-Phe-Leu-Ala-Ala OCH3 formation, an equilibrium yield was attained at 1:3.10(5) enzyme-substrates ratio that indicated high efficiency of pepsin in synthesis reactions. In the course of the equilibrium peptide synthesis, pepsin gradually disappeared from the liquid phase due to its entrapment within a gel, formed by the hexapeptide product, while retaining its activity. The inclusion into the precipitate was not specific for pepsin, so far as inert proteins, lysozyme, ribonuclease A and carbonic anhydrase, when added to the reaction mixture, became also co precipitated with the hexapeptide formed. It appears that co-precipitation of pepsin, an important factor limiting the enzyme efficiency, might be operative as well for other proteinases used to catalyze peptide synthesis. PMID- 1428532 TI - Continuous flow solid (gel) phase peptide synthesis using unsupported ultra-high load polymers. AB - A simple, manually operated, continuous flow apparatus is described for solid (gel) phase peptide synthesis. The approach uses an unsupported phenolic bead form core network at an initial matrix loading of 5 mmol g-1, the theoretical maximum. The synthesis is performed in a flow reactor under low pressure conditions. "Layered displacement" of reagent solutions and washing solvents is an essential feature that has been developed to facilitate efficient peptide synthesis. The usefulness of the present system in conjunction with N alpha Boc protected amino acids is illustrated by the syntheses of [Leu5]-enkephalin and dermorphin. The potential for scale up synthesis has also been investigated. PMID- 1428534 TI - Crystal structure of tert.-butyloxycarbonyl-L-prolyl-D-alanyl-D-alanyl-N methylamide. Dimeric beta-sheet formation. AB - The crystal structure of the tripeptide t-Boc-L-Pro-D-Ala-D-Ala-NHCH3, monohydrate, (C17H30N4O5.H2O, molecular weight = 404.44) has been determined by single crystal X-ray diffraction. The crystals are monoclinic, space group P2(1), a = 9.2585(4), b = 9.3541(5), c = 12.4529(4)A, beta = 96.449(3) degrees, Z = 2. The peptide units are in the trans and the tBoc-Pro bond in the cis orientation. The first and third peptide units show significant deviations from planarity (delta omega = 5.2 degrees and delta omega = 3.7 degrees, respectively). The backbone torsion angles are: phi 1 = -60 degrees, psi 1 = 143.3 degrees, omega 1 = -174.8 degrees, phi 2 = 148.4 degrees, psi 2 = -143.1 degrees, omega 2 = -179.7 degrees, phi 3 = 151.4 degrees, psi 3 = -151.9 degrees, omega 3 = -176.3 degrees. The pyrrolidine ring of the proline residue adopts the C2-C gamma conformation. The molecular packing gives rise to an antiparallel beta-sheet structure formed of dimeric repeating units of the peptide. The surface of the dimeric beta-sheet is hydrophobic. Water molecules are found systematically at the edges of the sheets interacting with the urethane oxygen and terminal amino groups. Surface catalysis of an L-Ala to D-Ala epimerization process by water molecules adsorbed on to an incipient beta-sheet is suggested as a mechanism whereby crystals of the title peptide were obtained from a solution of tBoc-Pro-D-Ala-Ala-NHCH3. PMID- 1428535 TI - Efficient approach to synthesis of two-chain asymmetric cysteine analogs of receptor-binding region of transforming growth factor-alpha. AB - The putative receptor-binding region of human transforming growth factor-alpha (TGF alpha) has been shown to be contributed by two fragments: an A-chain (residue 12-18) and a 17-residue carboxyl fragment (residue 34-50) that includes a disulfide-containing C-loop (residue 34-43). An approach to the synthesis of two-chain analogs containing an intermolecular disulfide linked A-chain and the 17-residue carboxyl fragment (C-fragment) possessing receptor-binding activity is described. The synthesis was achieved by the solid-phase method using the Boc benzyl protecting group strategy. The single Cys of the A-chain was activated as a mixed disulfide with 2-thiopyridine to form the intermolecular disulfide bond with Cys41 or Cys46 of the C-fragment on the resin support. Prior to this reaction, the acetamido (Acm) protecting group of Cys41 or Cys46 was removed by Hg(OAc)2 on the resin support. The peptide and side chain protecting groups including the S-methylbenzyl moiety of the Cys34 and Cys43 were concomitantly cleaved by high HF. The intramolecular disulfide with two unprotected Cys was formed in the presence of an intermolecular disulfide. This intramolecular disulfide bond formation was usually not feasible under the traditionally-held scheme at basic pH since disulfide interchange would occur faster than intramolecular oxidation. To prevent the disulfide interchange, a new method was devised. The intramolecular disulfide bond oxidation was mediated by dimethylsulfoxide at an acidic pH, at which the disulfide interchange reaction was suppressed. The desired product was obtained with a 60-70% yield.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428536 TI - Peptide crystal growth via vapor diffusion. Crystal structure of glycyl-L-tyrosyl L-alanine dihydrate. AB - The structure of a dihydrated form of glycyl-L-tyrosyl-L-alanine (GYA) has been determined as part of a series of peptide structural investigations and development of microscale vapor diffusion experiments for peptide crystal growth. Crystals were grown by the hanging-drop method against sodium acetate. The tripeptide is a zwitterion in the crystal, adopting an extended conformation through glycine, a nearly perpendicular bend at tyrosine and a reverse turn for the C-terminal carboxylate. Principal backbone torsion angles are psi 1 175(1) degrees, omega 2 173(1) degrees, phi 2 -119(1) degrees, psi 2 120(1) degrees, omega 3 172(1) degrees, phi 3 -73(1) degrees, psi 31 -9(1) degrees, psi 32 171(1) degrees. The tyrosyl side chain adopts an unusual orientation (chi 1/2 = -86(1) degrees). The relationship of the GYA.2H2O structure to GYA sequences in proteins is examined, particularly as regards its helix-forming potential. Crystal data: C14H19N3O4.2H2O, M(r) = 345.36, orthorhombic, P2(1)2(1)2(1), a = 4.810 (4), b = 11.400(7), c = 30.162(23)A, V = 1653.8(24)A-3, Z = 4, Dx = 1.387 Mgm-3, lambda(CuK- alpha) = 1.540 A, mu = 9.053 mm-1, F(000) = 736, T = 199 K, R = 0.041 for 1458 observations with I greater than or equal to 3 sigma(I). PMID- 1428537 TI - Application of arylsulphonyl side-chain protected arginines in solid-phase peptide synthesis based on 9-fluorenylmethoxycarbonyl amino protecting strategy. AB - One of the main problems still hampering solid-phase peptide synthesis using orthogonal protection strategies based on the 9-fluorenylmethoxycarbonyl amino protecting group is the difficult removal of currently used arginine arylsulphonyl guanidino protecting groups. Poor acid liability of 4-methoxy-2,3,6 trimethylbenzenesulphonyl-protected arginine has led to the popularity of the newer 2,2,5,7,8- pentamethylchroman-6-sulphonyl guanidino protecting group. This group was initially believed to have liability to trifluoroacetic acid, the reagent commonly used to simultaneously deprotect peptides and detach them from the synthesis resin, comparable to tert.-butyl and trityl type protecting groups used for the protection of other peptide side-chain functionalities. In a comparison of three established cleavage/deprotection mixtures we have shown that this is not always the case, particularly in multiple arginine peptides. We have found that only hard-acid deprotection with trimethylsilyl bromide reliably removed both arylsulphonyl guanidino protecting groups from a variety of arginine containing peptides. PMID- 1428539 TI - Effect of copper(II) chloride on suppression of racemization in peptide synthesis by the mixed anhydride and related methods. AB - In segment couplings by the mixed anhydride method using isobutyloxycarbonyl chloride, the use of copper(II) chloride as an additive suppressed racemization completely in the same manner as in the carbodiimide method reported previously. This was confirmed by employing a number of couplings between Z-dipeptides and amino acid esters. The racemization-suppressing effect of other compounds were also evaluated by employing one of these model couplings to be at best only limitedly effective. Copper(II) chloride was effective also in the related method using EEDQ. Thus, in the couplings where a low level of racemization was observed without an additive, the addition of copper(II) chloride eliminated racemization even at ambient temperature where EEDQ is usually used. The effectiveness of copper(II) chloride was confirmed also in the BOP-Cl method. In the presence of HOBt racemization was reduced to a low but still detectable level, while it was suppressed completely by the addition of copper(II) chloride. PMID- 1428538 TI - Unusual thionation of a cyclic hexapeptide. Conformational changes and dynamics. AB - One carbonyl oxygen of the cyclic hexapeptide cyclo(-Gly1-Pro2-Phe3-Val4-Phe5 Phe6-) (A) can be selectively exchanged with sulphur using Yokoyama's reagent. Surprisingly it was not the C=] of Gly1 but that of Phe5 which was substituted and cyclo(-Gly1-Pro2-Phe3-Val4-Phe5 psi [CS-NH]Phe6-) (B) was obtained. Thionation results in a conformational change of the peptide backbone although the C=O of Phe5 and the corresponding C=S are not involved in internal hydrogen bonds. Two isomers in slow exchange, containing a cis Gly1-Pro2 bond in a beta VIa-turn (minor) and a trans Gly-Pro bond in a beta II'-turn (major), were analyzed by restrained molecular dynamics in vacuo and in DMSO as well as using time dependent distance constraints. It is impossible to fit all experimental data to a static structure of each isomer. Interpreting the conflicting NOEs, local segment flexibility is found. MD simulations lead to a dynamic model for each structure with evidence of an equilibrium between a beta I- and beta II-turn about the Val4-Phe5 amide bond in both the cis and trans isomers. Additionally proton relaxation rates in the rotating frame (R1 rho) were measured to verify the assumption of this fast beta I/beta II equilibrium within each isomer. Significant contributions to R1 rho-rates from intramolecular motions were found for both isomers. Therefore it is possible to distinguish between at least four conformers interconverting on different time scales based on NMR data and MD refinement. This work shows that thionation is a useful modification of peptides for conformation-activity investigations. PMID- 1428540 TI - Synthesis and biological activity of the mono- and di-galactosyl-vespulakinin 1 analogues. AB - Syntheses are described of some mono- and di-glycosylated analogues of vespulakinin 1. The solid phase procedure, based on the Fmoc chemistry, was used to prepare (Gal alpha)Thr3-vespulakinin 1, (Gal beta)Thr3-vespulakinin 1 and the di-glycosylated analogue ((Gal alpha)Thr3, (Gal alpha)Thr4-vespulakinin 1. The beta-glycosylated derivative was also prepared by the continuous flow variant of the Fmoc polyamide method. The synthesized glycopeptides were purified and characterized by amino acid analysis, optical rotation, analytical HPLC, 1H- and 13C-NMR and FAB-MS. Preliminary pharmacological experiments showed that the carbohydrate-free vespulakinin 1 is less active than bradykinin (about 0.3 times on a molar basis) when tested by guinea pig rectum contraction, and the two monoglycosylated analogues are equiactive (about 0.9 times the bradykinin activity). The most active derivative, the (Gal alpha)Thr3, (Gal alpha)Thr4 vespulakinin 1 analogue, was about 2.5 times as active as bradykinin. PMID- 1428541 TI - Ethylcarbamoyl protection for cysteine in the preparation of peptide-conjugate immunogens. AB - During the solid-phase synthesis of over 100 peptides, we have observed that the ethylcarbamoyl group is useful for the side chain protection of cysteine in peptides containing a single cysteine residue. The ethylcarbamoyl group is stable to the conditions of acidolytic cleavage, purification and long term storage. Brief treatment of peptides containing an S-ethylcarbamoyl-cysteine residue with aqueous sodium hydroxide gives the deprotected cysteine peptide that can be coupled to carrier molecules such as proteins to give immunogen conjugates. PMID- 1428542 TI - FMOC solid phase synthesis of an endothelin converting enzyme substrate. Use of allyl ester as the third orthogonal protecting group. AB - The synthesis of a substrate for the endothelin converting enzyme using the continuous flow FMOC solid phase method has been accomplished. The allyl group, employed to protect Glu side chain, was cleanly removed during the synthesis in the presence of tert.-butyl based protecting groups to enable the introduction of the Edans moiety. The substrate was obtained in 31% yield after reverse phase hplc purification. PMID- 1428543 TI - Synthesis and conformation of the trimeric coiled-coil segment of laminin. AB - A disulfide linked 95-mer parallel hetero-trimeric active site segment of laminin was designed and synthesised. The three subunits, A (32-mer), B1 (30-mer) and B2 (33-mer), were prepared by Boc-based solid-phase peptide synthesis involving a two-step trimethylsilyl bromide-thioanisole and HF deprotection procedure. The interlinking of the three subunits was accomplished by the stepwise selective formation of two disulfide bridges using air-oxidation and thallium (III) trifluoroacetate oxidation. The conformations of the synthetic peptides were studied by circular dichroism (CD) spectroscopy, showing that the hetero-dimer, B1-B2, one of the homo-dimers, B1-B1, and the trimer are 30 to 40% in the alpha helical conformation in aqueous buffer. Variable temperature CD studies demonstrated that the trimer is considerably more stable (melting temperature (Tm) = 61 degrees) than the hetero-dimer, B1-B2 (Tm = 36 degrees). PMID- 1428544 TI - Central function and visual field damage in glaucoma. AB - 82 eyes of 82 patients with different types of glaucoma were examined with various psychophysical tests assessing central and paracentral function, including foveal temporal contrast sensitivity function, FM 100-Hue test, and foveal and parafoveal blue-on-yellow-sensitivity. For all eyes visual field tests were performed with the Humphrey-Field-Analyzer, program 30-2. Global visual field indices were calculated as follows: Mean Sensitivity MS, Mean Deviation MD, and Corrected Pattern Standard Deviation CPSD. Linear regression analysis and multiple regression analysis correcting for a possible influence of age between the central and paracentral criteria and the global indices was performed. For the entire study population highly significant correlations are present between foveal and parafoveal blue-on-yellow-sensitivity and MS, MD and CPSD. Whereas in the Normal Tension Glaucoma subgroup (19/82 eyes) no significant correlations are found, the subgroup of 35/82 eyes with markedly elevated intraocular pressure (> or = 30 mmHg) shows highly statistically significant correlations between the low and high-frequency end of the foveal temporal contrast sensitivity function and foveal and parafoveal blue-on-yellow-sensitivity and the global field indices. The results of the present study support the idea that there are two different mechanisms of glaucomatous damage, one which is pressure-dependent and one which may be pressure-independent. The pressure-dependent mechanism is responsible for deficits of central or paracentral function which are correlated to overall visual field damage. PMID- 1428545 TI - The pattern ERG in glaucoma: effect of pattern reversal time. AB - Pattern reversals with a ramp-like temporal course evoke transient pattern electroretinograms (PERG) that are delayed and attenuated in comparison with responses evoked by a step-like course (abrupt pattern reversals). This delay depends on the reversal time and probably represents a measure for temporal characteristics of the activated retinal structures. A pattern reversal stimulator with adjustable reversal periods (matrix of 8 x 14 rectangular red light emitting diodes, element size 2 degrees x 1 degree, stimulus area 16 degrees x 14 degrees) was used to record transient PERGs from 20 glaucomatous eyes with early or moderate visual field damages (measured with computer perimetry). The q-wave (P1) amplitude difference between the glaucoma group and normal subjects with step-like reversal stimulation was not significant (P = 0.23). On the other hand, a highly significant separation (P < 0.0001) between both groups was possible using the P1 latency at ramp-like stimulation or the response latency shift between step and ramp-like stimulation (Pattern reversal time, 30 ms). PMID- 1428546 TI - Is oculokinetic perimetry useful? AB - An evaluation was carried out comparing Oculokinetic Perimetry (O.K.P.) with Automatic Perimetry of Thresholds (Hipocampus Perimeter) for ocular hypertension and glaucoma studying 145 eyes. The O.K.P. shows a sensitivity between 35.65 and 38.54%, a specificity of 76.67-79.59%, a + predictive value of 78.72-85.42%, and a-predictive value of 23.71-39.80%. PMID- 1428547 TI - Oculokinetic perimetry compared with standard perimetric threshold testing. AB - To calibrate oculokinetic perimetry (OKP) as developed by Damato in terms of conventional perimetric threshold values, 33 eyes with either glaucoma or ocular hypertension were tested with a standard Humphrey Field Analyzer using the Central 30-2 test and twice with a 26-point OKP chart. The frequency of seeing of the OKP test spot was plotted against 30-2 thresholds. This showed a weak relation between the two tests. Subsequently eyes that were considered to have had poor fixation were omitted, but false positive and false negative results still occurred in 19 remaining eyes. To check whether Troxler's effect (local adaptation) might have caused false positives, 6 subjects were tested with OKP, controlling the fixation times. Increasing the fixation time from 'very short' to 2 and 5 seconds yielded more 'not seen' responses in OKP. False negative data were found to occur preferentially in border areas of visual defects. The average frequency of seeing curve over all data showed a 50% frequency of seeing for the OKP stimulus at a 14.6 dB equivalent conventional threshold value. The spreading of the curve was 7 dB (95% confidence interval 28 dB). PMID- 1428548 TI - Intra- and inter-observer variation of optic nerve head measurements in glaucoma suspects using disc-data. AB - The aim of this study was to determine the intra- and inter-observer variation in the use of a system designed for exact measurements from standard optic nerve head photographs. The commercially available system consisted of a colour CCD Videocamera, a dedicated frame grabber and customized software run on a IBM AT compatible computer. Masked measurements were made 3 times by 2 observers, from stereophotographs of the optic nerve head of 56 eyes from 30 glaucoma suspects. The cup was defined on the basis of contour, not pallor and the disc area was defined as the area inside Elschnig's ring. Intra-observer variances were 0.001 +/- 0.001 mm2 for cup area (mean +/- SD), 0.002 +/- 0.002 mm2 for disc area and 0.002 +/- 0.003 mm2 for rim area. These values for intra-observer variance were comparable with the results obtained using manual planimetric techniques. Intra observer variance for disc area was significantly larger for the less trained of the two experienced observers. Inter-observer variances were 0.004 +/- 0.009 mm2 for cup area, 0.008 +/- 0.013 mm2 for disc area and 0.009 +/- 0.014 mm2 for rim area. These inter-observer variances were significantly larger than those previously reported for manual planimetry. The absolute differences between the two observers ranged from -0.35 to +0.20 mm2 (-0.08 +/- 0.11 mm2) for cup area, from -0.38 to +0.15 mm2 (-0.08 +/- 0.11 mm2) for disc area and from -0.29 to +0.34 mm2 (-0.06 +/- 0.12 mm2) for rim area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428549 TI - Similarities between disc haemorrhages and thromboses of the retinal veins. AB - 999 patients with glaucoma (G) visited the office from the beginning of 1980 until the end of 1991. 381 patients with disc haemorrhages and 164 with thrombosis (T) were found and followed when possible. At the detection 17 cases with thrombosis and 41 cases with disc haemorrhage (H) had glaucoma. During follow-up 52 cases with glaucoma got a thrombosis and 26 cases with thrombosis developed glaucoma, 105 cases with glaucoma got a disc haemorrhage and 33 cases with disc haemorrhage developed glaucoma. At the end of the follow-up 179 cases with glaucoma have had a disc haemorrhage, and 95 have had a thrombosis. In this material disc haemorrhages and thromboses, both thromboses of a branch (TB) and thromboses of the central vein (TC), behaved in the same way with respect to the occurrence of glaucoma, and the hypothesis that the materials H, TB or TC are of similar origin and symptoms of glaucoma seems reasonable. PMID- 1428550 TI - Retinal nerve fiber layer defects and automated perimetry evaluation in ocular hypertensives. AB - Preliminary results of a larger investigation on correlation between Retinal Nerve Fiber Layer Defects (RNFL) and Automated Perimetry (AP) are presented. A group of ocular hypertensive patients was recruited and a cross-section, randomized study was carried out. The group was composed of 54 eyes from 28 patients; 15 men and 13 women, mean age 42.76 year, mean visual acuity 0.95 (Snellen cart) and mean visual defect expressed in diopters was +0.514 (from -2.5 to +5). A total of 17 (31.48%) refractive fields were pathologic according to our criteria, one from a normal RNFL and the others from nerve fiber defects. We observed 6 no reliable RNFL photographs, 18 normal, 11 slits, 6 wedge, 11 diffuse and 2 mixed defects. Comparing RNFL and AP, 53.33% of eyes with fiber defects had abnormal perimetries. The more evolutioned the defect, the larger percentage of abnormal visual fields were observed: 36.36% in slit defects, 66.66% in wedge, 54.55% in diffuse and 100% in mixed ones. Comparing location of defects with location of cluster of decreased sensibility points in visual field, a higher correlation in inferior than superior defects was found. PMID- 1428551 TI - Correlations between densitometry of red-free photographs and reflectometry with the scanning laser ophthalmoscope in normal subjects and glaucoma patients. AB - OBJECTIVE: To compare image measurements of the retina produced by scanning laser ophthalmoscopy with those from red-free photographs (RFP) of the nerve fibre layer. SUBJECTS: The left eyes of 23 subjects (10 normal, 7 glaucoma suspect and 6 glaucomatous) were included in this study. METHOD: All the eyes were photographed using standard red-free photography, and images of the retina were digitised directly from the SLO. RESULTS: The correlation coefficient for all except three subjects was > 0.45, and the probability (p) that R = 0 was < 0.05 in all but 5 eyes. CONCLUSIONS: The data indicate that variations in retinal surface reflectivity as measured by the SLO are similar to those recorded on negative film during RFP. This further suggests that the SLO can be useful for making objective measurements of the RNFL, without the intermediate and variable steps of photography. PMID- 1428552 TI - Diffuse nerve fiber layer loss in normal tension glaucoma. AB - 14 eyes of 14 normal tension glaucoma (NTG) patients with the maximum intraocular pressure (IOP) > or = 19 mmHg and 16 eyes of 16 NTG patients with the maximum IOP < 19 mmHg were examined. All patients had a scotoma confined to the upper or lower hemifield. Eyes with the maximum IOP > or = 19 mmHg showed significantly diffuse retinal nerve fiber layer (RNFL) loss in the RNFL area corresponded to the spared visual hemifield as compared to those with the maximum IOP < 19 mmHg. The results suggests that, even in NTG, IOP may be an important factor causing optic nerve damage. PMID- 1428553 TI - Spectrometric investigations in ocular hypertension and early stages of primary open angle glaucoma and of low tension glaucoma--multisubstance analysis. AB - The approximation of logarithmic difference spectra between the reflectance of the normal fundus and the fundus reflectance in different stages of glaucoma is demonstrated by a model. The influences of fundus pigments like oxihemoglobin, melanin, xanthophyll and rhodopsin as well as the intensity and the exponent of the scattered light are optimized. Glaucomatous alterations in the extinction of these pigments and of the scattering parameters are different in the macula, in the papillo-macular bundle and in the parapapillary region temporal to the optic disc. A lack of oxihemoglobin only in the papillo-macular bundle in first relative losses in the visual field function points to a damaged microcirculation in early POAG. In progressive glaucoma the extinction spectrum of xanthophyll is detectable in the papillo-macular bundle. A decreased intensity of the scattered light and an altered scattering exponent are suggestive of a damage in the nerve fiber layer at early stages of glaucoma. PMID- 1428554 TI - Optic nerve fiber loss in relation to atrial fibrillation and blood pressure. AB - This study investigates the relationship of atrial fibrillation, systemic blood pressure and nerve fiber loss. 213 institutionalized glaucoma patients (mean age 83.9 years) and 100 control patients (mean age 81.8 years) were examined ophthalmologically and analyzed for blood pressure. A 12-lead electrocardiogram, analyzed according to the Minnesota code, was taken for 212 glaucoma patients and 100 control patients. 17% of the glaucoma patients had atrial fibrillation (AF), which was significantly more than in the control group (8%). Patients with AF had lower systolic blood pressures (mean 146.5 mmHg) than the other patients (mean 153.7 mmHg). Visual acuity (VA) of the patients having AF was lower than that of the other patients. Severe visual field defects occurred more frequently in patients having AF (in 70% v.s. 42%). Patients with severe visual field defects and lower VA had lower systolic blood pressures than the patients with better visual fields and VA. 75% of geriatric glaucoma patients with AF and 64% of geriatric glaucoma patients without AF had intraocular pressures < 18 mmHg. Atrial fibrillation and low systolic blood pressure are connected with impairment of ocular functions of geriatric glaucoma patients. PMID- 1428555 TI - Anatomical risk factors in primary angle-closure glaucoma. A ten year follow up survey based on limbal and axial anterior chamber depths in a high risk population. AB - A population of 539 persons was examined in 1979, using LCD and ACD estimations acc. to van Herick et al. and by Haag Streit pachymetry, respectively. ACD had been measured already in 1969, due to a remarkable occurrence of primary angle closure glaucoma (PACG) in the survey population of Greenland Eskimos (District of Uummannaq). The present follow up study in 1989 aimed at persons presently above age 40, who had shown either an LCD value graded as 0 (contact) or 1 (< 0.25 of corneal thickness = CT), or a value of 2 (= 0.25 CT) if an ACD value of < = 2.70 mm (CT included) had also been found. PACG patients or suspects known in 1979 already were excluded from the present analyses. A total of 75 persons was now examined. Five had developed acute (n = 2) or intermittent PACG (n = 3) during the ten year period. At the survey 3 intermittent and 4 latent PACG cases were detected, yielding in ten years a PACG prevalence of 12/75 = 16% (sex ratio: M/F = 2/10). One male case of severe secondary (partly inflammatory) ACG was also found. Past and present LCD and ACD values are given as well as gonioscopical status. Creeping, synechial angle-closure was frequent. Among probands who could not be examined, mostly due to death before 1989, 5/54 had developed PACG during the ten year period. Non-probands according to above criteria were mostly not examined. Yet their records were scrutinized for any event suspect of PACG. Thus among 258 persons above age 40 no PACG case was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428556 TI - Color Doppler imaging in evaluation of optic nerve blood supply in normal and glaucomatous subjects. AB - The authors evaluate by means of Color Doppler Imaging (CDI) the blood flow in ophthalmic artery, posterior ciliary arteries and central retinal artery in a group of glaucomatous patients. The data obtained in this study show a statistically significant reduction of the mean systolic peak flow velocity in ophthalmic artery in glaucomas in comparison with controls. In Glaucomatous patients with uncontrolled IOP there was a reduction of end-diastolic flow velocities and a rise of resistivity index in ciliary arteries and central retinal artery. PMID- 1428557 TI - Pr VECPs related to ciliary perfusion pressure in primary open angle glaucoma. A study using contact lenses to compensate for refraction changes during artificially raised IOP. AB - Pr VECP studies in glaucoma patients with the IOP raised artificially by the suction cup method have recently been performed by several authors, who arrived at different results. The reason for those differences may be the changes employed. The refraction changes depend on the shape of the suction cup and the height of the artificial IOP raise. By using contact lenses and a suitably shaped suction cup refraction changes could be compensated for. Studies of the pr VECP with suction cup IOP elevation and simultaneous compensation for refraction changes by applying contact lenses were made on 17 patients with primary open angle glaucoma and 21 healthy volunteers. In healthy subjects pr VECP amplitudes were found unaltered or even slightly increased until 120 mmHg of negative pressure were reached in the cup. Beyond that range they dropped. Latencies remained unaltered over that range of negative pressures. Plotting the pr VECP amplitudes and latencies against ciliary perfusion pressure we obtained unaltered potentials over a range of ca. 20 mmHg, which we interpreted as autoregulative capacity. In the 17 glaucoma patients various degrees of impaired autoregulation were found corresponding to the progression of glaucoma damage. PMID- 1428558 TI - Axial and para-axial fluorophotometry in glaucoma simplex. AB - In this fluorophotometric study, in 25 eyes with middle advanced stages of glaucoma simplex (visual field defects ranged from 500 dB to 800 dB) and treated with topical antiglaucomatous agents, the posterior vitreous penetration ratio (PVPR) was compared with that from normal subjects. Vitreous fluorophotometry (Fluorotron Master, Coherent) was used to measure posterior vitreous fluorescein concentration. Due to additional fixation light in horizontal plane, three scans were taken along the following directions: temporal (t), foveal (f), nasal (n). The angle of deviation from the foveal scan was 15 degrees in each direction. The average values of posterior vitreous penetration ratio in group of patients with glaucoma were higher in comparison with those in healthy subjects. In both groups the PVPR was significantly lower in nasal (n) scan (optic disc area) in comparison with temporal (t) or foveal (f) scans (p < 0.05). PMID- 1428559 TI - X-PERT NCT advanced logic tonometer valuation. AB - The air pulsed automatic tonometer X-PERT NCT has been tested in hospitals on glaucomatous patients. This new technique avoids direct contact with the patient's eyes and therefore avoids any risk of contamination. The population studied consisted of 118 eyes of 60 patients whose intraocular pressure (I.O.P.) is measured by applanation with the Goldmann tonometer and then by the air pulsed tonometer. The average I.O.P. obtained by Goldmann tonometer is 17.5 +/- 5 mmHg while by X-PERT tonometer, the average I.O.P. is 17.4 +/- 1.5 mmHg. Statistical analysis of these data showed a very good correlation (r = 0.969) in the two methods of measurement. PMID- 1428560 TI - A clinical evaluation of XPERT NCT (Reichert) for glaucoma screening by optometrists. AB - XPERT NCT advanced logic pneumotonometer (Reichert) was studied for its reliability and use in glaucoma screening. The evaluated 2400 NCT measurements on 300 eyes were compared to the results of Goldmann applanation tonometry (GAT) from the same eyes. Repeated NCT tonometry had no significant effect on IOP. Local anesthesia reduced mean NCT-GAT difference and standard deviation significantly (p < 0.05), i.e. feeling due to the diminished air pulse force provided by the instrument had still considerable influence on IOP. NCT-GAT regression was significant (p < 0.01). Mean IOP readings provided by NCT were four mmHg higher than GAT values. Although accuracy was not satisfactory for exact measuring, it was satisfactory for screening. The results suggested that four mmHg less than the mean IOP value seen on the display is acceptable for screening when the difference between the minimal and maximal individual readings on the display is less than 2SD i.e. six mmHg. In the case of a greater difference, the maximal value is to be replaced, as NCT tends to read higher values than GAT. PMID- 1428561 TI - The Pulsair-Keeler non-contact tonometer in self-tonometry: preliminary results. AB - The authors considered the possibility of using the Pulsair-Keeler non-contact tonometer in self-tonometry. For this reason, 45 patients have been trained to use the instrument and, after a reasonable trial period, were able to self measure their IOP. The results have been compared to the tonometric values measured with Goldmann tonometer to evaluate statistically the limits and the dependability of this method of measurement. The results shows that self tonometry with the Pulsair-Keeler tonometer can be used in monitoring glaucomatous patients at home. PMID- 1428563 TI - Does aqueous humor secretion decrease with age? AB - Aqueous humor flow was calculated during day-time in 148 healthy volunteers and 75 older patients using the Fluorotron Master II anterior chamber protocol (Coherent, Palo Alto, USA). Healthy volunteers as well as patients had no history of ocular pathology, surgery or laser treatment. Slitlamp examination revealed no ocular pathology. Hypertension, diabetes, local and systemic drug therapy, neoplasia, kidney or liver disease, contact lens and ocular trauma were excluded. Mean age of volunteers was 26.5 +/- 3.8 years; age of patients: 65.5 +/- 10.5 years. Aqueous humor flow during day-time in healthy volunteers in the OD: (mean +/- s.d.) 2.26 +/- 1.0 microliters/min, in the OS: 2.17 +/- 1.0 microliters/min, OS: 1.86 +/- 1.1 Ml/min. Correlation coefficient: r = 0.8. The mean aqueous humor flow in the older patients during day-time: OD: 1.91 +/- 1.1 microliters/min. Correlation coefficient: r = 0.54. The Mann-Whitney-U-test revealed a significant difference when comparing the right eyes of healthy volunteers with the right eyes of patients (p < 0.01). When comparing all left eyes the difference is also significant (p = 0.01). The results of the study underline, that the mean aqueous humor secretion does significantly decrease with age. However, the data show that there is only a slight decrease of flow of approximately 2.5% per decade. From the clinical point of view it should be concluded, that although the aqueous humor secretion does decrease with age, this is not of clinical importance, even in cases of glaucoma surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428562 TI - Self-tonometry: technical aspects of calibration and clinical application. AB - Self-tonometry could be established as an important diagnostic tool in the early diagnosis and follow-up of glaucoma provided that a self-tonometer is precise, safe and easy to use. Furthermore, it has to comply with the legal standards for tonometer calibration. A new software-controlled detection system for the self tonometer permits the evaluation of external factors during the measurement which influence the precision of the tonometric readings. The updated version of the self-tonometer (ST) was compared to the Draeger hand-held applanation tonometer (HAT) in a clinical study with 82 patients (151 eyes). The results show a regression line characterized by a slope of 0.99, an y interception of 1.41, a correlation coefficient of 0.96 and a standard deviation for the ST readings of +/- 1.78 mmHg. Self-tonometry improves the IOP monitoring as well as patient compliance and therefore is a potential diagnostic tool in the management of glaucoma. PMID- 1428565 TI - Study on the aqueous humor flow measured by fluorophotometry after argon laser trabeculoplasty. AB - We have investigated the variations in the aqueous humor flow (F) after argon laser photocoagulation (ALT) in the trabecular meshwork. The research has been done on 60 eyes with primary open angle glaucoma within initial stages. The argon laser trabeculoplasty was made around 360 degrees in anterior trabecular meshwork with 100 burns. The flow (F) has been studied by fluorophotometry using Yablonsky's protocol. Aqueous humor flow has been measured after 24 hours and after 7 days, to determine the immediate effects of laser trabeculoplasty; and also after 6 months for the long term effects. The initial aqueous humor flow was 1.35 microliters/min. By means of ANOVA we found statistically significant differences on aqueous humor flow after the 7th day (F = 1.67 microliters/min, p < 0.01), which remain six months later (F = 1.71 microliters/min, p < 0.01). This findings suggest that the effects of argon laser trabeculoplasty, either by mechanical or biological changes in the trabecular meshwork do not appear until the 7th day and remain throughout the follow up study. PMID- 1428564 TI - A fluorophotometric study on the aqueous humor dynamics in primary open angle glaucoma. AB - One hundred and ten eyes in 40 normal persons with no ocular pathology, 20 with ocular hypertension and 50 with primary open angle glaucoma were studied. The value of the aqueous humor flow was obtained and then compared with the different samples and with general (age, sex) and ocular factors (intraocular pressure, tonographic outflow facility, campimeter and disk/cup ratio, among others). PMID- 1428566 TI - Long-term drift and timolol therapy: possible role for pulsed therapy. AB - Eyes treated with a topical betablocker may exhibit the phenomenon of longterm drift, leading to loss of intraocular pressure control. It has been suggested that discontinuation of the betablocker may restore sensitivity to betablocker therapy, and that this phenomenon might be enhanced by the administration of an adrenergic agonist during this holiday period. This study was set up to examine further this hypothesis. Nine patients with ocular hypertension receiving treatment with timolol were entered into the study. Timolol was discontinued then re-started after four weeks of treatment with dipivefrin. This treatment cycle was repeated after a further four weeks. IOP was measured every two weeks. Re introduction of timolol was associated with a significant lowering of IOP at two weeks (3.2 mmHg in the first cycle, p < 0.01, 3.4 mmHg in the second cycle, p < 0.01). Discontinuation of timolol and treatment with dipivefrin was not associated with a significant change in IOP. PMID- 1428567 TI - Effects of timolol on visual-field mean retinal sensitivity in normal subjects. AB - This single-blind, randomized study investigated the effects of unilateral instillation of 0.5% maleate timolol twice a day for 7 days on visual-field parameters of both eyes. Twelve normal, young subjects (30.6 +/- 4.2 years) participated in this study. Using program G1 of the Octopus 500 automated perimeter, the visual fields were measured one week and one day before therapy and a third time one week after beginning therapy. The paired T-test was used for statistical analysis, where a P-value < or = 0.05 indicated significance. Whereas nothing statistically significant was found in the treated eyes, the contralateral, untreated eyes showed a statistically significant decrease of mean sensitivity between the first visual fields and the third ones (P < 0.01) This diminution of mean sensitivity in the untreated contralateral eyes may be due to statistically significant lowering of blood pressure (P < 0.01) and slowing of cardiac frequency, which were not compensated by a local decrease of intraocular pressure. If confirmed, these findings could be of clinical importance in the management of glaucoma patients, since some authors have, in some cases, recommended a unilateral therapy. PMID- 1428568 TI - Changes in depressive status associated with topical beta-blockers. AB - Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients. PMID- 1428570 TI - Changes in the ocular dimensions after trabeculectomy. AB - Ocular wall dimensions (axial eye length, anterior chamber depth, lens thickness, vitreous length, thickness and volume of the ocular wall) were determined by echobiometry on 10 eyes of 10 patients with glaucoma one day before and four days after trabeculectomy. The results showed significant differences: decreased axial eye length, and increased thickness and volume of the ocular wall were found after trabeculectomy. The observed changes in the ocular dimensions might be due to ocular hypotony and postoperative inflammation. Echographic follow-up of the changes in the ocular wall is a useful monitor to study alteration in eye dimensions after glaucoma surgery. PMID- 1428569 TI - The effects of dopamine, haloperidol and bromocriptine on intraocular pressure. AB - In a double-blind randomised, prospective single dose study, we measured intraocular pressure (IOP), pupil diameter, systemic blood pressure and heart rate in 43 ocular normotensive subjects before (baseline) and 2, 4, and 6 hours after topical instillation of the following drugs: dopamine 2% (n = 11), a dopamine receptor blocking drug, haloperidol 0.5% (n = 11), a dopamine receptor stimulating drug, bromocriptine 0.05% (n = 11) and 0.1% (n = 10). In the groups receiving dopamine or haloperidol, there were no significant differences in IOP compared with baseline values (p > 0.01). But, a significant decrease in IOP compared with the baseline values was found in both bromocriptine groups (p < 0.001). With the 0.05% and 0.1% concentrations, maximum reductions in intraocular pressure were 22.0% +/- 5.8% and 28.4% +/- 9.8%, respectively. No significant differences in mean pupil diameter, systemic blood pressure and heart rate were detected in all of these groups. In addition, in the group receiving bromocriptine 0.1%, there was no change in serum prolactin levels. These results suggest that topically administered bromocriptine has satisfactory intraocular pressure lowering capacity without serious ocular or systemic side effects. Consequently we conclude that, an ophthalmic formulation of bromocriptine may have substantial clinical potential for the treatment of glaucoma. PMID- 1428571 TI - Therapeutical and genetical aspects of congenital glaucomas. AB - Therapy for congenital glaucoma is primarily surgical. We have investigated 249 cases who have undergone trabeculectomy. There was a 79% success rate as regards to control of the IOP. Vision could be saved among the patients who had applied relatively early. At the end of the follow up which was 5 years IOP remained normal in the successful group. All the patients and their families were analysed genetically by their pedigrees and caryotypes. An autosomal recessive pattern with variable penetrance was found. The majority of the patients came from families with consanguineous marriages giving a rate of 66.6%. It was suggested that the course of the disease is highly affected by and related to parental consanguinity. An early age of onset and an accelerated clinical course could be well correlated. PMID- 1428572 TI - Photoablative filtration surgery with the excimer laser for primary open-angle glaucoma: a pilot study. AB - We have performed ab-externo photoablative filtration surgery on 19 patients affected by uncontrolled primary open-angle glaucoma. All cases had wide open angles, were previously treated with argon laser trabeculoplasty and were considered good candidates for trabeculectomy. After topical and peribulbar anesthesia, a limbus-based conjunctival flap was dissected. Photoablation of a rectangular area at the limbus was performed with an argon fluoride excimer laser (193 nm), at 180 mJ x sq cm fluence. The beam was shaped in the appropriate fashion using a custom-made metal mask. Photoablation was continued until aqueous appeared percolating through the juxtacanalicular tissue at the bottom of the crater; a water-tight closure of conjunctiva was then performed. Postoperatively, the anterior chamber reaction was minimal; in no case a flat chamber or choroidal detachment was observed. In 18 of the 19 cases the IOP was significantly lowered, and a filtering bleb developed. Mean preoperative IOP was 26.4 (+/- 7) mmHg. At a median follow-up of 9 months (range 4-15) the IOP is < or = 18 mmHg on no medications in 16 (84%) of the eyes, with a mean value of 13.3 (+/- 6) mmHg. Our short-term results support excimer laser photoablative filtration as a relatively safe and effective procedure for primary open-angle glaucoma. PMID- 1428573 TI - Daunorubicin versus 5-fluoro-uracil in surgical treatment of primary open angle glaucoma: a prospective study. AB - In a prospective randomized study, we compare the results at 20 months of 5 Fluoro-Uracil and Daunorubicin filtering surgery in two groups of 25 patients with primary open-angle glaucoma. For the first group of 14 eyes, 10 injections of 5FU are done and only one subconjunctival preoperative injection of Daunorubicin in the second group of 13 eyes. 5FU group consists of 13 patients: 9 males, 4 females. The mean age is 52.3 +/- 18.4 years. The mean follow-up is 6.9 +/- 7 months. Daunorubicin group consists of 12 patients: 9 males, 3 females. The mean age is 50.2 +/- 21.4 years. The mean follow-up is 7.3 +/- 7 months. By Kaplan-Meier method, the probability success rate is 79 per 100 with 5FU and 68 per 100 with Daunorubicin. After 5FU procedure, the most disturbing complication is related to the decrease in IOP during the first postoperative days: flat anterior chamber (9 eyes) (7 eyes after Daunorubicin), choroidal detachment (6 eyes) (2 eyes after Daunorubicin), cataract (3 eyes in the two groups). After Daunorubicin, corneal complications are less frequent: corneal ulcer (2 eyes) (3 eyes after 5FU), corneal dystrophy (1 eye in the two groups). Transient chemosis and local palpebral oedema are constant after Daunorubicin. We compared the IOP reduction rate and visual function loss in the two groups. PMID- 1428575 TI - Long term follow-up of the argon laser trabeculoplasty in eyes treated 180 degrees and 360 degrees of the trabeculum. AB - The results obtained with the Argon Laser Trabeculoplasty (ALT) on 196 eyes with an average follow-up period of 5.24 years (maximum 9 years) have been reviewed. Of the 123 eyes treated with 75-115 burns in the 360 degrees of the trabecular meshwork, 71 eyes were successful with a follow-up of 64.3 +/- 28.3 months (mean +/- SD). This treatment reduced the previous anti-glaucomatous medical treatment in 35 eyes (28.5%). The remaining 73 eyes were treated with 40-60 burns in 180 degrees of the trabeculum, 38.4% (28 eyes) were successful therapeutically with a follow-up of 56.5 +/- 23.1 months. The treatment reduced the additional medical treatment in 9 eyes (12.3%). The comparison of these results and the survival curves of both groups showed statistically significant differences in favour of the treatment on 360 degrees of the trabeculum. PMID- 1428574 TI - Mitomycine, suterelysis and hypotony. AB - In 35 patients 37 trabeculectomies (TE) were performed using mitomycin as a fibrosisinhibitor. Mitomycin (0.5 mg/ml) was applied to the sclera (under the scleral flap) and conjunctiva in the area of the projected TE during 5 minutes using a small sponge. The indications for operation were: visual field progression in 15 eyes, too high IOP in 13 eyes and severe visual field defects (central island and/or centro coecal visual field defects) in 9 eyes. Six patients had Normal Pressure Glaucoma, 17 Primary Open Angle Glaucoma and 12 had other forms of glaucoma. There were 22 first TE's and 15 re-operations. The scleral flap was sutured with 5 to 8 10/0 nylon sutures. The system of a large number of sutures and subsequent suturelysis was our routine management for reducing complications after TE. This report deals with the postoperative period of the first three months. Suturelysis in combination with mitomycine caused an unexpected high number of postoperative hypotonies (IOP < = 6 mmHg with reduced visual acuity and/or retinal folds or large persistent choroidal detachment and shallow anterior chamber) In the 27 eyes who had suturelysis performed, 7 developed a hypotony. The hypotony may develop as late as three weeks postoperative after suturelysis!. Two eyes developed a hypotony without suturelysis. Seven patients needed resuturing of the scleral flap. The use of mitomycine to enhance filtration after TE may cause serious hypotonies if the scleral flap is not securely closed and if suturelysis is used too early or too extensively. PMID- 1428577 TI - Promotion of glaucoma filter bleb with tissue plasminogen activator after sclerectomy under a clot. AB - Since 1987 we have performed, with good results, glaucoma filtering surgery in which the limbo-scleral fistula was closed by an autogenic full blood clot (sclerectomy under a clot). In 8 patients with advanced stages of glaucoma simplex, 1-3 days after sclerectomy under a clot with rise IOP, 25 micrograms of tissue plasminogen activator (tPA) was injected subconjunctivally. Two weeks after surgery normalization of IOP below 15 mmHg and normal outflow facility in all tPA treated eyes were obtained. No increase in early post-operative complications, such as hemorrhage or corneal haze, was attributable to tPA use. In early period after sclerectomy under a clot, when blockage of outflow appears, the use of tPA can cause the re-creation of filtering tract. PMID- 1428576 TI - Intraoperative and post operative treatment with 5-fluorouracil and mitomycin-c: long term effects in vivo on subconjunctival and scleral fibroblasts. AB - Rabbits undergoing full thickness glaucoma filtering surgery were exposed to one of 4 treatments. Group 1 received intraoperative distilled water, group 2 received intraoperative mitomycin-c 0.2 mg/ml for 5 minutes, group 3 received 5 post operative injections of 5-Fluorouracil (5-FU) 5 mg in 0.1 ml, and group 4 received intraoperative 5-FU 50 mg/ml followed by 5 post operative injections of 5-FU. 30 days after the operation tissue biopsies were taken from the subconjunctival and scleral tissue at the treated area and 90 and 180 degrees from the treated area. The biopsies were then placed in tissue culture media and the outgrowths quantitated. The fibroblast outgrowths from all areas did not differ significantly from each other except for the outgrowths from the areas directly treated with mitomycin 0.2 mg/ml which were significantly smaller. In addition then cells were morphologically abnormal although there were foci of normal cells which appeared to be growing from localised areas in the tissue biopsies. The outgrowths from the areas 90 and 180 degrees from the treated area were normal. Intraoperative treatments with mitomycin-c result in long term inhibition of fibroblast proliferation limited to the treated area, when compared with intraoperative and postoperative treatment with 5-FU. Failure of filtration surgery in eyes treated with intraoperative mitomycin may in part be due to unaffected cells reproliferating. PMID- 1428578 TI - Improved suture for fornix-based conjunctival flap in filtering surgery. AB - Major problems in the early postoperative phase in filtering surgery are hypotony, flattening of the anterior chamber and choroidal detachment. We describe a new suture technique for the closure of the conjunctiva in goniotrephination with a fornix-based conjunctival flap which is helpful in reducing these complications. After dissecting the conjunctiva from the limbus, a shallow groove is cut directly behind the former conjunctival insertion. At the end of the operation the conjunctiva is sutured into this groove using a running 10.0 nylon suture in a meander-like fashion. A very tight wound closure results. We used this technique in 104 consecutive goniotrephinations. We found a low incidence of only mild external fistulation, hypotony, flattening of the anterior chamber and choroidal detachment. Astigmatism induced by the operation was -1.2 +/- 1.2 D, usually with the rule. PMID- 1428579 TI - Treatment of glaucoma following penetrating keratoplasty with transscleral YAG cyclophotocoagulation. AB - Thirteen patients with refractory glaucoma following penetrating keratoplasty were treated with 180 degree transscleral Neodymium: YAG cyclophotocoagulation. Intraocular pressures below 21 mmHg were achieved in nine patients (69%) with a mean follow up of 19.8 months. Multiple treatments were required in six patients and graft decompensation occurred in five. No patient developed hypotony. Transscleral YAG cyclophotocoagulation is a useful alternative to further surgery in some patients with glaucoma following penetrating keratoplasty. PMID- 1428580 TI - The effect of high-intensity focused ultrasound on intraocular pressure in therapy-resistant glaucoma 3-4 months and 1 year after treatment. AB - The effect of therapeutic ultrasound for the treatment of refractory glaucoma was evaluated in 44 patients by comparing average IOP curves measured before and 3-4 months after treatment. The insonification regime was standardized and the glaucoma medication in each individual patient was unchanged during IOP curve measurements. The average IOP decrease 3-4 months after insonification was 42.2% +/- SD 31.9. In 23 patients who were followed for at least one year the average IOP 3-4 months after treatment was compared with the average IOP 1 year after treatment. In this group average IOP 3-4 months after treatment was 25.3 mmHg +/- SD 16.4 and average IOP 1 year after treatment was 24.1 mmHg +/- SD 15.9. The correlation coefficient between IOP 3-4 months after treatment and IOP 1 year after treatment was 0.79 (P < 0.0001). PMID- 1428583 TI - [The validity of infant mortality statistics in Navarra]. AB - In order to explore the validity of official infant mortality statistics, the number of infant deaths registered in the cohort of live births and resident in Navarra (Spain) from 1985 to 1989, according to data supplied by the Department of Statistics of Navarra, has been compared with that obtained in a retrospective search into the information of the hospitals. Among 24,383 live births of the cohort, 291 were certified as infant deaths. An over-register of 13 cases (4.5%) and an under-register of 26 cases (8.9%) was detected. By excluding those live births with less than six months of gestation, as done by the National Institute of Statistics, the validity is altered, because apart from the errors mentioned, one must add those resulting from the incorrect filling-in of the "number of weeks pregnant"= variable. When correcting these deficiencies, the final statistics (Infant Mortality Risk = 11.17 per 1000 live births) did not differ much from the official figures (IMR = 11.48 per 1000 live births). PMID- 1428581 TI - Surgical management of closed angle glaucoma: our experience. AB - In this paper we present our experience of the last three years in the surgical treatment of eyes with closed angle glaucoma. We have performed an extracapsular lens extraction and posterior chamber intraocular lens implantation on 34 eyes of 34 patients. All of them were affected by closed angle glaucoma with variable control after a Yag laser iridotomy: 6 eyes had high I.O.P. notwithstanding maximal therapy, 11 eyes had I.O.P. under control (less than 21 mmHg) without therapy, 9 with I.O.P. controlled with topical therapy, 8 with I.O.P. controlled with maximal therapy (C.A.I. included). The cases with well controlled glaucoma were operated on because of the presence of a more or less significant lens opacities. After a follow-up of up to 40 months (mean = 20.3, range = 1-40), all eyes show satisfactory intraocular pressure and no eye needed a filtering procedure. The results of our studies are as follows (values are mean +/- SD). In the group of 6 eyes with high I.O.P., the mean pre-operative intraocular pressure was 29.7 +/- 5.6 mmHg and the mean post-operative I.O.P. was 15.1 +/- 1.4 mmHg. The mean reduction was 14.5 +/- 6.6 mmHg (p < 0.005). In the 28 eyes with pre operative I.O.P. under control (17.5 +/- 1.6), the mean post-operative I.O.P. was 14.4 +/- 2.3 mmHg, with a mean reduction of 3.1 +/- 3.1 mmHg (p < 0.005). Before the E.C.C.E., 11 eyes had I.O.P. less than 21 mmHg without anti-glaucoma medication, whereas after the E.C.C.E. 28 eyes did not need such a medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428582 TI - Combined small-incision cataract surgery and trabeculectomy--technique and results. AB - In a prospective study 35 eyes of 25 patients with coexisting cataract and glaucoma underwent trabeculectomy, phacoemulsification and implantation of a folded polyHema intraocular lens through the trabeculectomy opening. Follow-up ranged from 6 to 27 months (mean 13.3). The mean age was 76.4 (68 to 88 years). 22 eyes suffered from primary open angle glaucoma, 10 eyes from a pseudoexfoliation glaucoma and 3 eyes had a chronic angle closure glaucoma. Preoperatively intraocular pressure was controlled in 10 eyes with a mean medication of 2.1 but uncontrolled in 25 eyes (mean medication: 2.5). The preoperative visual acuity ranged from 20/40 to hand motions. Postoperatively intraocular pressure was controlled (< 18 mmHg) in all (100%) eyes and without therapy in 32 (91%) eyes. Three (9%) eyes had to be treated with topical timolol twice a day after surgery. Mean intraocular pressure dropped from 21.2 +/- 6.0 mmHg preoperatively to 13.5 +/- 2.1 mmHg postoperatively. Vision improved in all but 4 eyes, 25 (74%) achieving a visual acuity of 20/40 or better. The causes for failed improvement or deterioration of vision were senile macular degeneration in 2 eyes and central retinal vein occlusion and vascular optic nerve atrophy in one eye respectively. Post-operative complications included hyphema in 9 (26%) eyes, fibrin effusion to a various extent into the anterior chamber in 19 (54%) eyes and delayed hypotony (< 5 mmHg) with chorioidal effusion in 1 (3%) eye. Fibrin effusion was frequently observed in eyes with intraocular pressure below 10 mmHg, iris surgery and hyphema. Finally the complications did not effect the results regarding visual acuity or glaucoma control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428584 TI - [Adolescence at risk: a health survey among pre-university students]. AB - The present study investigates the level of health education in a representative sample of 804 pre-university Asturian students, randomly selected from the official list of the Ministry of Education and Science. We used a questionnaire (designed by us) in order to measure the knowledge, attitudes and behaviour related to some of the most important health determining factors. The survey was carried out by interviewing small groups of students in the classroom situation. Although it was found that the majority perceived themselves as healthy or very healthy, these young people are widely exposed to risk factors: 12% have suffered from more than 25 episodes of drunkenness during the previous year; 43.53% smoked to some extent and only 3.86% identified the days of maximum risk of pregnancy in a supposed menstrual cycle, although 31% maintained sexual relationships. Theoretically, 92% selected health as the most important factor among the three most fundamental values for life. They also think that illegal drugs are the most important health problem at present for young people. There is a contradiction between the high theoretical importance given to health, the good self qualification of it, and the observed presence of important risk factors. A certain failure of the educational system with respect to primary prevention can be claimed. PMID- 1428585 TI - [Traffic accident mortality in Catalonia and other autonomous communities (1983 1990)]. AB - With the aim to understand road accident mortality in Catalonia, death certificates were studied, and a comparison between several autonomic communities was undertaken to highlight any differences. The road accident death rate increased from 9.8 in 1983 to 19.4 per 100,000 inhabitants in 1990. By 1990, the death rate for Catalan males was 31.3 per 100,000 inhabitants, and 7.9 for women, figures which showed increases of 90% and 50%, respectively, since 1983. Standardised mortality rates for Galicia, Asturias and Valencia have, on average, been higher those for Catalonia and Madrid (p = 0.014). Catalonia is the community which has experienced the greatest increase, with an evolution showing a good linear fit (p = 0.005). PMID- 1428586 TI - [Blood pressure, physical activity and anthropometry in adolescents]. AB - The relationship of blood pressure with physical activity and anthropometry was studied in 295 adolescents (mean age, 15.3 years) who entered 1. "formacion profesional" (a technological training) in 1990 in Puerto Real, a village of Cadiz, Spain. Systolic and diastolic (fifth-phase Korotkoff) blood pressure, and anthropometrics measurements (weight, height and triceps and subscapular skinfolds thickness) were measured with standardized techniques. Habitual and sports physical activity were assessed by a self-reported questionnaire. The results reported in this study suggest that systolic blood pressure is associated with habitual physical activity in girls, and that the systolic blood pressure is associated weakly with sports activity in girls and in boys. The stronger predictor of blood pressure was Quetelet Index (kg/m2). PMID- 1428588 TI - [Hatred is the worse contaminant]. PMID- 1428587 TI - [The measurement of satisfaction in health services]. AB - The satisfaction analysis in health services has been object of rising interest recently. The different instruments of measurement known show the diversity of conceptualism, range of applications and methodologies. The article revises selectively and not exhaustively different instruments as well as the approximations to the concept of satisfaction from the marketing disciplines and the investigations in health services. Special emphasis is dedicated to the analysis of satisfaction in hospital services and the use of questionnaires for its measurement. PMID- 1428589 TI - Tympanometry and otoscopy prior to myringotomy: issues in diagnosis of otitis media. AB - Tympanometry and pneumatic otoscopy were compared to findings at myringotomy in 86 children (163 ears). Seventy percent of the ears (115) had effusion, as revealed by myringotomy. Sensitivity and specificity for tympanometry were 90% and 86%, respectively. Sensitivity and specificity for pneumatic otoscopy were 93% and 58%, respectively. A chi-square was performed to compare the sensitivity and specificity to tympanometry to otoscopy, revealing tympanometry significantly better at determining non-effusion states. Additionally, a combined otoscopy and tympanometry sensitivity and specificity were calculated for those otoscopy and tympanometry determinations in agreement, revealing both sensitivity and specificity above 90%. A Fisher's exact probability test revealed no significant differences for the accuracy of tympanometry over otoscopy when the determinations of each were not in agreement. Implications of these results are discussed. PMID- 1428590 TI - Atopy and environmental factors in upper respiratory infections: an epidemiological survey on 2304 school children. AB - Upper respiratory infections (URI) during the first years of life are mostly viral in origin. However, a number of observations suggest the influence of both predisposing and triggering factors. Atopy in particular seems to play an important role as do environmental factors. Many children with early symptoms such as blocked or runny nose are likely to become skin-positive later in life to antigens such as, e.g., D. pteronissinus. A standardized questionnaire was administered to 2304 schoolchildren in order to ascertain the URI frequency and to correlate it with family and environmental factors and with results of prick tests for main allergens in our climate (D. pteronissinus and Grasses). Results showed a wide overlapping of URI and lower respiratory illnesses (in particular, asthma), which are widely distributed in the families of patients. Passive smoking and the quality of housing are the main triggering environmental factors. In our sample, skin positivity for D. pteronissinus and Grasses largely exceeds the symptomatic portion of the whole population. It is therefore suggested that many asymptomatic children are "at risk" for allergic respiratory illness. The highest incidence of winter rhinitis in skin-negative subjects (71.7%) and the skin positivity for D. pteronissinus in patients with perennial symptoms, suggest the importance of both atopy and viral infections in the occurrence of URI. Nasal troubles are most frequent in asthmatic subjects and may be considered the actual additional symptom in asthma. PMID- 1428591 TI - Distribution characteristics of immunoglobulin-secreting cells in adenoids. Relationship to age and disease. AB - Forty-four adenoids and 52 palatine tonsils from 71 children and adolescents (age 3-21 years) undergoing surgery because of adenoidal hypertrophy or recurrent tonsillitis were examined for the presence of immunoglobulin-secreting cells (ISC) employing an enzyme-linked immunospot assay (ELISPOT). ISC constituted less than 2% of the mononuclear cell population. Adenoids contained IgG, IgA, and IgM ISC in significantly lower numbers than palatine tonsils. The predominant isotype of the ISC was IgG, in adenoids accounting for 62% of the ISC and in palatine tonsils for 73%. The relative numbers for IgA and IgM ISC were similar. A significant correlation existed between autologous adenoids and palatine tonsils for the numbers of IgA and IgM ISC, but not for the numbers of IgG cells. These observations suggest that, adenoid and palatine tonsils display similar immunoglobulin distribution patterns within a single individual. However, individuals with hypertrophied adenoids exhibited a numeric decrease in IgG ISC with increasing age (P less than 0.01). Both lymphoid tissues may be involved in mucosal immune defense. PMID- 1428592 TI - Serum immunoglobulin E levels in children with chronic tonsillitis. AB - Serum immunoglobulin E (IgE) levels were estimated by ELISA in 50 children with chronic tonsillitis before and after tonsillectomy. When compared with the control group, mean serum IgE concentration was found to be significantly higher in children with chronic tonsillitis (P less than 0.001). After tonsillectomy the levels returned to normal. PMID- 1428593 TI - CT evaluation of tracheobronchial tumors in children. PMID- 1428594 TI - Why and how should we study infant cry? AB - The study of the acoustics of infants' vocalizations has important implications for the study of infant development and for clinical prediction. We suggest procedures that enhance the probability of discriminating among sub-glottal, periglottal, and supraglottal sites of pathology, With these procedures, then, it should become possible to contribute to diagnosis and therefore to treatment. PMID- 1428595 TI - Congenital abnormalities of the submandibular duct. AB - Five newborns presented with cystic lesions of the floor of mouth. Four of these patients proved to have congenitally imperforate submandibular salivary gland ducts and the other newborn proved to have a duplication anomaly of the submandibular gland duct and gland. The patients with imperforate Wharton's ducts underwent marsupialization with or without ductoplasty and have been without evidence of recurrence for up to three years. The duplication anomaly of the submandibular gland duct responded to simple excision. The diagnosis of congenital anomalies of the submandibular gland and duct can be made on physical examination. Magnetic resonance imaging can be helpful in differentiating congenital imperforate submandibular duct and duplication anomalies of the ductal system. Treatment of the former consists of duct marsupialization in the floor of mouth with or without ductoplasty. Treatment of the duplicated ductal system may best be treated with excision. A failure in diagnosis and treatment may result in ranula formation or sialoadenitis requiring more extensive therapy. PMID- 1428596 TI - Epipharyngeal teratoma in infancy. AB - Epipharyngeal teratomas are rare congenital lesions that often cause respiratory distress, stridor at birth. The management of such anomalies should include establishment of secure upper airways, radiographic exclusion of midline CNS malformations and early surgical excision to prevent malignant transformation, asphyxia or permanent facial distortion. The diagnosis of congenital stridor, dyspnea and rhinitis should be performed very carefully. PMID- 1428597 TI - Contribution of MR in the diagnosis of 'occult' posterior laryngeal cleft. AB - This paper reports three cases of 'occult' submucous posterior laryngeal cleft in which MR examination has visualized the deficiency of the posterior cricoid lamina. Laryngeal cleft is an uncommon anomaly, and its clinical and endoscopic diagnosis is always difficult. To our knowledge, the role of MR in this diagnosis has not yet been emphasized. PMID- 1428598 TI - Apnea and the elongated uvula. AB - Four cases of respiratory distress and apnea associated with an elongated uvula are presented. In all cases, the uvula was found to intermittently fall onto the epiglottis and vocal cords. In all four patients, resection of the uvula led to resolution of all airway symptoms. It is hypothesized that the uvula, touching the vocal cords, caused intermittent laryngospasm and subsequent symptoms of cough, airway obstruction, and cyanosis. The anatomic reasons for such phenomenon are discussed. PMID- 1428599 TI - Faculty/student perception of organizational climates in the schools of nursing, Oyo State, Nigeria. AB - This study examined the influence of educational status and gender on the faculty and students' perceptions of their school climates. A self-designed questionnaire was used to elicit information from the 385 subjects (320 students and 65 tutors). Analysis using the t-test technique revealed that there were no significant differences at the 0.05 level of probability in the perceptions of: (a) faculty and students on climate variables "thrust" (t = 0.31) and "control" (t = 1.19); and (b) both sexes on climate variables "thrust" (t = 1.69), "control" (t = 1.13) and "disengagement" (t = -0.53). The conclusion therefore, is that educational status and gender have little or no influence on the peoples' perception of their school climates. PMID- 1428600 TI - Students' and lecturers' preferred teaching strategies. AB - A survey of lecturers (n = 47) and students (n = 110) was undertaken to explore their preferred teaching strategies, using a questionnaire based on Heron's (1977) Dimensions of Facilitator Styles (Human potential research project, University of Surrey, Guildford). Overall it was found that the students tended to prefer a teacher-centred approach to teaching, whilst the lecturers preferred a student-centred approach. These findings are discussed in the light of current educational trends in the nursing profession. PMID- 1428601 TI - Positioning of the stroke patient: a review of the literature. AB - Stroke is a common and disabling illness, adversely affecting the quality of life of hundreds of people each year. While there are many therapeutic approaches to stroke patient rehabilitation, encouraging patients to adopt "reflex-inhibiting" patterns of posture is a widely advocated strategy for helping patients to avoid complications of hemiplegia such as spasticity and contractures. However, while the central role of nurses in thus helping patients is recognized, the influence of posture on recovery from stroke has never been evaluated. Prior to undertaking such an evaluative study, texts on stroke patient care were reviewed to clarify the received view about the recommended positioning for patients with hemiplegia. Consensus on some issues was evident (such as positioning the patient with the affected shoulder protracted, spine straight, fingers extended and avoiding external rotation of the affected hip). However, opinion was divided on others and a number of potentially important aspects were ill-covered. This paper integrates a summary of the findings of this review with the physiological rationale for the recommendations. The main areas of agreement are highlighted and issues as yet unanswered are raised for further consideration. PMID- 1428603 TI - Patients' night-time pain, analgesic provision and sleep after surgery. AB - One hundred patients were interviewed about their experiences of pain and sleep following abdominal surgery. This information was supplemented by data on analgesic provision which were gathered from medication charts. Pain was the most commonly reported cause of night-time sleep disturbance and analgesics helped more patients to get back to sleep than any other intervention. About half of the patients felt that pain was worse at night than during the day. An examination of patterns of analgesic provision revealed that the number of doses given peaked at two points during the 24-hour cycle. The highest numbers of doses were given between 8 a.m. and 12 noon and 8 p.m. and 12 midnight. Fewer doses were given at night, between midnight and 4 a.m. Analgesic provision at night, therefore, did not appear to be explicitly related to need. The assessment and control of post operative pain at night requires further attention in order to optimize pain control and promote sleep. PMID- 1428602 TI - Resistance to documentation--a nursing research issue. AB - In this case study, the views of a sample of four hospital nurses were elicited to determine underlying causes of persistent antipathy towards documentation in patients' charts. The results of this review supported a common belief that resistance to charting is influenced by extrinsic, or environmental factors, such as inflexibility of charting systems and insufficient allocation of time. In addition, intrinsic factors or cognitive and psychosocial factors, not emphasized in earlier studies, such as lack of confidence about written expression, a tendency to succumb to group norms governing charting and difficulty in articulating the nature of nursing practice, surfaced as impediments to documentation. This review suggests that a broader study approach is required; one that addresses intrinsic, as well as extrinsic, factors. PMID- 1428604 TI - The need for graduate nursing education and nursing research in The Netherlands: an exploratory study. AB - In 1989 research was performed aimed at discovering the views of Dutch administrators of intramural health care institutions on the need for graduate nursing education and nursing research in The Netherlands. The study was completed in 1990. Because the research aim was to learn the informants' point of view, a grounded theory method was applied. The sample size was 13. The subjects were selected by using two separate sampling procedures, so as to minimize bias. Data were collected by means of semi-structured interviews of 1 hour, which were tape recorded and transcribed verbatim. Analysis of the data was done by using the constant comparative method, involving concurrent collection, collation and analysis. The three major themes that finally emerged from the data analysis were named Change, Problems and Solutions. In order to keep as open a mind as possible the systematic review of the literature was done after the field work and analysis of the data. This article presents the findings and the implications of the study. PMID- 1428606 TI - The use of guided tissue regeneration to facilitate ideal prosthetic placement of implants. AB - Placement of implant fixtures in an ideal position for restoration is not often possible using standard protocol, because most patients lack sufficient bone in the alveolar process. To facilitate ideal restorative placement of implant fixtures, principles of guided tissue regeneration can be used to provide adequate bone and prevent dehiscence and fenestration of the implant. Four cases of such treatment are presented. PMID- 1428605 TI - Empirical evidence shows that measuring users' opinions is not a satisfactory way of evaluating computer-assisted learning in nurse education. AB - Users' opinions have been one of the cornerstones of the evaluation of both CAL, in general, and CAL packages, in particular, in nurse education. This paper reports on two experiments that reliably show student nurses' opinions of their current computer-use are formed more by the change from a previously-used computing facility rather than the actual features that the current one possesses. The use of such opinions as a valid evaluation measure within nursing CAL is, consequently, weakened. The evaluation context in which these experiments are conducted derives from the highly-researched multidisciplinary area of Human Computer Interaction (HCI), and the experiments are introduced and discussed with respect to the HCI concepts of computer-use and usability which examine the interactions taking place at the human-computer interface. Graphical hypertext and the doctrine of functionality are also introduced and discussed, for these aspects have considerable implications for computer-use and the process of planning and choosing computer-use facilities within nurse education. PMID- 1428608 TI - Initiating restorative procedures at the first-stage implant surgery with a positional index: a case report. AB - With the use of a positional index, the restorative dentist and laboratory technician can be provided with an accurate record of implant fixture location after first-stage surgery. Thus it is possible to fabricate a master cast with implant analogs and initiate laboratory procedures immediately after first-stage surgery, and a provisional restoration can be processed and delivered at the time of second-stage surgery. A case report is presented to illustrate the technique. PMID- 1428607 TI - Guided tissue regeneration in interproximal defects in the monkey. AB - The potential for guided tissue regeneration was evaluated in one-walled interproximal sites in Macaca fascicularis. Histologic differences were evaluated at 1 and 3 months. Within the experimental (barrier) group, 100% of the root surfaces with potential for regeneration were covered with new cementum, whereas the control specimens had 20% or less new cementum. The amount of regeneration was determined by the position of the barrier membrane; the more coronal the barrier, the greater the regeneration. Observations indicated that the optimal time for barrier removal is between 1 and 3 months. PMID- 1428609 TI - Clinical response to the use of the HTR polymer implant in human intrabony lesions. AB - Fifteen patients, men and women aged 18 to 65 years, were treated for periodontitis. Each patient had at least two bilateral intrabony defects; one was designated the experimental site and the other the control site. Both sites were surgically debrided, but one osseous defect received an HTR polymer implant. Patients were followed for 12 months postoperatively. Maximum pocket reduction occurred within 2 months of initial therapy in both experimental and control sites. Initially, pocket reduction was significantly greater in implanted sites than in control sites, but this difference did not occur subsequently. At the end of the 12 months, pocket reduction responses were similar at control and implanted sites. PMID- 1428610 TI - Gelb depth gauge: a diagnostic aid in implant placement. AB - Case reports describe the use of a radiographic depth gauge in conjunction with computerized axial tomography. This gauge identifies for the surgeon the precise site of implant preparation that will not only be in accord with anatomic vital structures, but also achieve parallelism with adjacent teeth and other implant sites. Discrepancies in angulation can be corrected, and maximum suitable fixture length can be determined. PMID- 1428611 TI - A clinical evaluation of hand and ultrasonic instruments on subgingival debridement. 1. With unmodified and modified ultrasonic inserts. AB - This clinical investigation evaluated the effect on subgingival surfaces of three instruments: hand instruments and ultrasonic instruments with modified and unmodified inserts. Ten operators (five dentists and five dental hygienists) performed randomly assigned operative procedures. Pocket depth, instrument limit, and instrument efficiency were evaluated for each type of instrument. The results indicated that there are advantages to using modified ultrasonic inserts for scaling and root planing. PMID- 1428612 TI - Cement thickness and microleakage under metal-ceramic restorations with a facial butted margin: an in vivo investigation. AB - Ten metal-ceramic restorations with buccal porcelain butt margins and palatal metal beveled margins were fabricated for periodontally hopeless teeth. After cementation, the experimental crowns remained in the oral environment for 3 to 6 months; the teeth were then extracted and used for microscopic and microleakage evaluation. All ten crowns showed at least a small amount of microleakage, but adaptation of beveled margins proved to be superior to that of shoulder porcelain margins. PMID- 1428614 TI - Surface EMG topography and pain distribution in pre-chronic back pain patients. AB - The relationship between surface EMG recordings from paraspinalis recording sites and subjective pain ratings were examined in a group of pre-chronic back pain patients. thirty-eight back pain patients without major orthopedic diagnosis and a pain duration between 2 to 6 months participated in a three week long subjective pain rating. Following the completion of their pain diary, the paraspinal sites were assessed under the "static" postural conditions of sitting and standing using an EMG scanning procedure. Results of the correlational analysis revealed significant and positive relationships between pain and muscle activity in the upper back (Trapezius, T1 paraspinalis sites) and significant but negative relationships between erector spinae activity (L3 paraspinalis site) and pain. When considering etiological factors of pre-chronic back pain, the results support both the organicity model for upper back, as well as the biomechanical model for the lower back. PMID- 1428613 TI - Spinal patterns as predictors of personality profiles: a pilot study. AB - The present pilot study is part of an ongoing effort to further the investigation of the relationship between spinal patterns and personality. The present pilot study seeks to identify likely spinal patterns of certain personality profiles and asks whether changing posture can affect personality, and/or can emotional states alter posture? Forty patients of a private chiropractic practice participated in the study. Four radiographs (x-rays) of each subject were taken and each subject completed the Minnesota Multiphasic Personality Inventory (MMPI). Measurements obtained from the radiographs and the MMPI data were used to derive general linear models of the predictability of the MMPI in terms of the spinal/postural measures. Several models were highly significant and preliminary support for the authors' hypothesis that spinal patterns are likely to be predictive of personality profiles is suggested. Support for previous research is offered and directions for future research are discussed. PMID- 1428615 TI - Self-regulation and assessment approaches for vaso-occlusive pain management for pediatric sickle cell anemia patients. AB - An interdisciplinary program with the goal of teaching self-regulation and minimizing excessive narcotic use in the management of vaso-occlusive pain (V-O) in pediatric sickle cell anemia patients is described. A small group of patients do not respond well to any of our outpatients or inpatients medical regimens, leading us to suspect that psychological factors are influencing pain reports. We outline our multi-faceted assessment approach to evaluating such psychological factors, which includes a pain flow sheet, symptom check list, and a psychophysiologic profile. Published reports of self-regulation training including biofeedback, relaxation/imagery, and hypnosis have been associated with decreased pain symptoms, reduced number of emergency room and hospital visits for pain, decreased narcotic use, and increased school attendance. A case study of a nine-year-old patient with sickle cell disease is described before and after self regulation training. Finally, other alternative approaches that avoid excessive narcotic use are discussed with some case reports. PMID- 1428616 TI - Managed care in psychosomatic medicine: a tale of three patients. PMID- 1428617 TI - Anorexia nervosa as manifested in Russia. AB - The authors describe current theoretical and clinical conceptualizations and treatment of anorexia nervosa in Russia, based on their experience in the follow up of 800 patients. Three-quarters of the patients exhibited anorexia nervosa linked with a border-line state, and one-quarter associated with schizophrenia. Different relationships to dysmorphophobic fears were observed in the different anorexic groups. In the border-line group, follow-up study indicated that the clinical symptoms of anorexia nervosa were significantly reduced. However, the disorder preserved its connection with dysmorphophobic fears even in the remote stages of the disease, and in later stages there was an occurrence of pathological personality changes. In the second group, from the very beginning, anorexia nervosa in schizophrenia was closely connected with affective disorders, pathological body sensations, hypochondriacal complaints, and a gradual personality deterioration. As the schizophrenic defect increased, anorexia nervosa was reduced to an exhausted form of vomiting behaviour, and lost its connection with dysmorphophobic experiences. PMID- 1428618 TI - Relaxation as an altered state of consciousness: a rationale for a general theory of relaxation. AB - A general theory of relaxation is presented. It is based on an integrated model of the main states of consciousness, which enables one to differentiate "techniques for relaxing" leading to the "relaxing states" and "meditative techniques" leading to the differentiated waking states of consciousness. These latter include specific "only the relaxation response states" and the "ultraconsciousness states". Each state is described along the following dimensions: of biological rhythms, i.e., Sleep-Wakefulness and the Basic Rest Activity Cycle; brain hemispheric activity; the threshold of the extero- and interoceptive stimuli reception; perceptual dominance of stimuli from external or internal sources; spontaneous versus goal-oriented imagination activity, i.e., passive or active state of mind; feed-back relation with the surroundings. PMID- 1428619 TI - Clarification of the concept of psychological stress ("psystress"). AB - The concept of "stress" in the current academic literature is unstandardized, and therefore confusing. The theoretical approach of regarding stress as an intervening variable seems most generally agreed on by researchers; the unambiguous term "Psystress" proposal to denote the mental state involved. Aspects of vocabulary concerning psystress production and response are also discussed. PMID- 1428620 TI - Hassles, life events, and health status among Chinese college students in Hong Kong. AB - Major life events and daily hassles were examined in a sample of 102 university undergraduates. While the major clusters of events were related to personal loss, life-style changes, family conflict, and personal insecurity, those of hassles were related to drudgery and uncontrollable environmental irritants, personal concerns, time and work management, minor routine expenses, and the dilemma of emigration. Using life events and hassles, and hassle clusters added significantly to the sensitivity of the concurrent prediction of undifferentiated and differentiated physical and psychological symptom criteria, and consistently showed better performance as predictors. However, the independent contributions of events and event clusters could hardly be discounted. The combined effects of major discrete and minor chronic stress on health status and the limitations of the present retrospective study were discussed. PMID- 1428621 TI - Pavlovian conditioning of phobic fear: effects on skin and salivary pH. AB - This experimental work was designed to investigate the relationships between pH and conditioned fear. The levels of pH were measured in skin and saliva, and were studied in connection with conditioned electrodermal and heart rate (HR) responses (extinction versus resistance to extinction or enhancement). The results of this investigation show that the changes in skin and salivary pH have a tendency to occur in an inverse pattern to the changes in skin conductance and HR. The data are interpreted in terms of skin and salivary pH as new psychophysiological variables and as new tools for psychopathological and psychosomatic research. PMID- 1428622 TI - Adverse effects of meditation: a preliminary investigation of long-term meditators. AB - Adverse effects of meditation were assessed in twenty-seven long term meditators (average 4.27 years) both retrospectively (time one) and prospectively at one month (time two) and six months (time three) following a meditation retreat. At both time one and time three subjects reported significantly more positive effects than negative from meditation. However, of the twenty-seven subjects, seventeen (62.9%) reported at least one adverse effect, and two (7.4%) suffered profound adverse effects. When subjects at time one were divided into three groups based on length of practice (16.7 months; 47.1 months; 105 months) there were no significant differences in adverse effects. How the data should be interpreted, and their implications both for the clinical and psychotherapeutic use of meditation as a relaxation/self-control strategy, and as a technique for facilitating personal and spiritual growth, are discussed. Limitations of the study and suggestions for future research are also offered. PMID- 1428623 TI - Psychophysiological effects of stimulation with pictures of works of art in old age. AB - The present article reports on a controlled intervention study concerning the effects of non-directed use of pictures of works of art as a way of stimulating institutionalized elderly women. After the stimulation period differences in ratings between the groups indicated improved well-being in the intervention group. Such improvement was not seen in the C-group. The quantitative analyses of the results reveal a significant change of the parameters happiness, peacefulness, creativeness, social activities and systolic blood pressure. The qualitative analysis shows that the conversations about pictures of works of art in the intervention group give the person free rein to her own imagination and are merely characterized by happiness. In the control group the conversations are to a great extent characterized by downheartedness, despair and complaining. PMID- 1428624 TI - Referral patterns of dentists: analysis and implications of a questionnaire. AB - The interpersonal and psychodynamic aspects of the referral process, that is, the reciprocal relationship between the specialist and his referral source are investigated. A questionnaire designed by the author, with anonymity guaranteed, was given to the members of 2 dental societies. There were more similarities than differences in the answers of the respondents in both groups. Several conscious patterns of referral emerged or were evident. A number of unconscious, psychodynamic motivations were explored. PMID- 1428625 TI - Prolactin and weeping. AB - Fourteen women with functional hyperprolactinemia and an equal number of matched healthy controls completed a questionnaire on weeping behavior. Contrary to expectations the patient group were not more prone to weeping than the controls. In addition, their appraisal of weeping behavior (as a way to tension release and relief) did not differ from the controls. It is concluded that moderately elevated prolactin levels, although causing somatic disturbances such as amennorrhea and galactorrhea, do not affect the weeping threshold. PMID- 1428626 TI - Creative psychotherapy and the facilitation of insight. AB - The following case studies provide insight into the effectiveness and methodology of the facilitation of insight technique in psychotherapy. This technique has been successful in reducing the incubation process, which is the second of four stages in Wallas's Stage Model of Creativity, i.e., Preparation, Incubation, Illumination and Verification. The application of this technique in other areas of human endeavor are discussed. PMID- 1428627 TI - Alcohol and narcotics. Epidemiology and pregnancy risks. AB - Among alcohol and narcotics, alcohol is most comprehensively documented as a teratogen. However, for all other narcotics, data are continuously accumulating, convincingly displaying the teratogenic effects. The proportions between "somatic" teratogenicity and "behavioral" teratogenicity vary between the different agents. Preventive work in prenatal clinics and among social workers, as well as objective mass media attention to the problem, seems to have lowered the incidence of severe fetal alcohol syndrome where the above-mentioned activities have been practiced. The female alcohol consumption in Sweden decreased from 1976 to 1985; thereafter, a slow continuous increase is underway again. In Sweden the number of recruits to narcotic abuse peaked in the 1970s and early 1980s. Thereafter, the number of recruits among females decreased, but abuse has continued among the members of the older age groups. PMID- 1428628 TI - Diagnostic and preventive possibilities of excessive drinking in antenatal care. AB - Alcoholism among women has increased during the last decades. Thus it is likely that an increasing number of pregnancies will involve risk of alcohol damage to the fetus. In this article, two antenatal programs are presented to identify pregnancies at risk. Adequate alcohol information seems to be sufficient for socially drinking women, whereas alcoholic women need extensive support to abstain from alcohol. The psychosocial support was not experienced as intrusive. PMID- 1428629 TI - Perspectives of users of the services. AB - This article draws on social science evidence concerning the views and experiences of those using the antenatal services. It identifies several important themes in this evidence, including the need to consider pregnancy a normal process, to provide care that is sensitive to individual circumstances and that offers continuity of care throughout the antenatal period, and the obligation on providers to assess scientifically the effectiveness of the care they give. PMID- 1428631 TI - Measuring the effectiveness of psychosocial interventions in pregnancy. AB - Questions about the effectiveness of psychosocial interventions in pregnancy are important in any overall evaluation of antenatal care. This article reviews the evidence as to the positive benefit on a range of pregnancy outcomes provided by 35 published and unpublished randomized controlled trials of psychosocial interventions. PMID- 1428630 TI - Prevalence and significance of social and psychological risk factors during pregnancy. AB - Moderate psychosocial problems identified during early pregnancy in 78 women were found to predispose for various "complications" during gestation, but not for prematurity or obstetrical complications during delivery. However, from a normal postnatal status the children of these mothers demonstrated a significantly unfavorable somatic, as well as psychomotoric development, until the age of 4. Pregnant women with certain psychosocial problems must be early identified and property attended to in order to preclude an adverse child development. PMID- 1428632 TI - Norwegian experiences. Competence of the providers and compliance to the treatment program for antenatal care in Norway. AB - Antenatal care was established in Norway during the 1930s. Unlike the other Nordic countries, care is provided by general practitioners, not be midwives. Guidelines were first issued in 1984 after a debate about the quality of the care. This article reports providers' compliance to important parts of the guidelines. PMID- 1428633 TI - Small-for-gestational-age (SGA) definitions and associated risks. AB - Samples and methods vary in constructing birthweight charts. Introduction of ultrasound dating affects the distribution of gestation, increases the proportion of preterm births, and reduces postterm and small-for-gestational-age (SGA) births. The need for standardized charts is emphasized. Preferably such charts ought to be sex- and parity-specific, also taking into account the mother's previous pregnancy outcome in terms of birthweight. The risks associated with being born SGA involve various morbidity as well as short- and long-term survival. PMID- 1428634 TI - Antenatal screening and risk factors for intrauterine growth retardation. AB - Antenatal risk factors in combination with symphysis-fundus distance can identify pregnancies with small infants, who can be divided in genetically small, malformed, and malnourished infants. Only the last category benefit from fetal surveillance. Maternal diseases, pregnancy complications (hypertension), and environmental factors (smoking) are connected to malnourished small infants. PMID- 1428635 TI - Prediction of fetal growth deviations by use of symphysis-fundus height measurements. AB - The development of various symphysis fundus (SF) growth charts and the use of SF height measurements in the diagnosis of small-for-gestational-age (SGA) births and the prediction of newborn complications are reviewed. Measurement precision and accuracy are also discussed. It is concluded that further research of this simple, low cost, harmless, and widespread technology to detect fetal growth disturbances in routine prenatal care is warranted. PMID- 1428636 TI - Antenatal diagnosis of intrauterine growth retardation by ultrasound. AB - Ultrasound estimation of fetal weight or ultrasound measurement of fetal abdomen alone enables identification of small-for-gestational-age fetuses. A prerequisite for this is a reliable dating of pregnancy, which is provided by a routine ultrasound screening in the first half of gestation. The fetal growth can be followed by serial fetometric measurements. As a standard, charts of intrauterine growth based on the ultrasonic measurement can be used. As a secondary diagnostic test for monitoring fetal health in pregnancies suspected of intrauterine growth retardation, Doppler ultrasound evaluation of fetal and uteroplacental hemodynamics provided useful for early detection of imminent fetal distress. PMID- 1428637 TI - Detection of intrauterine growth deviation. A comparison between symphysis-fundus height and ultrasonic measurements. AB - Efficacy of ultrasonography to detect fetal growth retardation is reviewed. Ultrasound dating is held as a prerequisite. Abdominal anthropometry is reported to reflect fetal growth best. Efficacy of symphysis-fundus (SF) height measurements is reviewed similarly. Proposed protocols that include ultrasound and SF height measurements and other maternal characteristics with known prognostic properties are reported. Preferably, both kinds of measurements should be analyzed longitudinally. PMID- 1428638 TI - The prognostic significance of antenatal diagnosis of fetal growth retardation. AB - Intrauterine growth retardation is associated with high risk of perinatal asphyxia. The neonatal mortality rate of small-for-gestational-age (SGA) infants (birthweight < or = 2 SD) in Sweden decreased from 5.6% in 1973 to 2.0% in 1987. During the same period, the number SGA infants with postnatal asphyxia (5 min Apgar score < 7) decreased from 10% to 5%. Based on antenatal diagnosis of fetal growth retardation, an optimal time of delivery reduces the risk of major neurological and developmental sequelae of the individual infant. PMID- 1428639 TI - Assessing the scientific basis of antenatal care. The case of Sweden. AB - The Swedish routine program for antenatal care is based on a number of scheduled visits for the detection of symptomless complications, as well as psychosocial support and health education. The scientific evidence to support the present timing and contents of routine visits is unsatisfactory, and there is a great need for evaluation both of single diagnostic procedures and interventions and of programs of antenatal care. PMID- 1428640 TI - Competence and compliance in antenatal care. Experience from Sweden. AB - Swedish antenatal care is staffed by midwives working within the primary health care system, but with close collaboration with the hospital. The compliance to the program both from staff and mothers is very high, with 13.2 visits on average. There is a regional variation both in the number of visits and in the use of routine tests. PMID- 1428641 TI - Antenatal care in Denmark. Assessments of program, staff competence, compliance, and outcome. AB - Antenatal care in Denmark is shared between general practitioners, midwives, and hospital departments. A minimum of 9 visits is officially recommended for all pregnant women. In 1987, 80% made 10 or more visits. An inadequate number of visits in relation to recommendations was most frequent in the lowest social group. Risk of stillbirth and neonatal death varied substantially between social groups even after taking account of number of visits made. PMID- 1428642 TI - Methodological problems and possible endpoints in the evaluation of antenatal care. AB - Antenatal care is evaluated based on observational trend studies, geographical comparisons, medical audits, and randomized trials. The last method is preferable and should be applied whenever feasible. Most components of antenatal care have not been properly evaluated. In order to evaluate an antenatal care program, a randomized study is suggested using geographical areas as units of randomization. PMID- 1428643 TI - Randomized controlled trials in the evaluation of antenatal care. AB - Many of the practices carried out during antenatal care improve the well-being of mother or baby and reduce the burden of adverse perinatal outcome. Other practices have either not been evaluated or have been shown to be ineffective. Evidence from randomized clinical trials provides the best evidence about the effectiveness of these practices. PMID- 1428644 TI - Register studies and clinical studies in the evaluation of antenatal care. AB - The advantages and limitations of national registers containing individual identification numbers in clinical epidemiological research are reviewed. The author concludes that such registers are very valuable for epidemiological research and for formulation of research questions of public health importance. PMID- 1428645 TI - Problems and prospects in the economic evaluation of antenatal care. AB - Economic evaluations can be used to compare alternative antenatal care programs in terms of cost and outcome. The cost of routine antenatal care is small compared to the total cost associated with pregnancy and childbirth. The main problem in economic evaluations is related to outcome measurement. PMID- 1428646 TI - Epidemiology of hypertension during pregnancy. AB - Hypertension during pregnancy, defined as a diastolic blood pressure of at least 90 mm Hg, occurs in about 7% of Western countries. Primiparity and familial factors are the most important risk factors. Fifty percent of women experienced blood pressure elevation as late as the last month of pregnancy. PMID- 1428647 TI - Screening for hypertension in pregnancy. AB - The literature dealing with screening for hypertension in pregnancy was reviewed. No level of blood pressure or any other factor provides a guarantee of no risk for the development of preeclampsia. However, higher blood pressure in early pregnancy and a failure to decrease blood pressure in mid-pregnancy are both associated with the development of preeclampsia. The development of proteinuria, rather than the level of blood pressure, is the best predictor of poor pregnancy outcome. Multiparas, especially those with severe chronic hypertension who develop preeclampsia, are at greatest risk of poor pregnancy outcome. PMID- 1428648 TI - Diagnostic methods for pregnancy hypertension. Significance of standardized conditions. AB - Standardized conditions for blood pressure measurements and strict definitions of systolic and diastolic blood pressure are essential for a consequent management of hypertension during pregnancy. In Sweden, it has been agreed to measure blood pressure with the pregnant women sitting in upright position. Home-monitoring of blood pressure is recommended in women at risk of preeclampsia. PMID- 1428649 TI - Cost-effectiveness of present programs for detection of asymptomatic hypertension in relation to the severity of hypertension and proteinuric hypertension. AB - Proteinuric hypertension is an important cause of maternal and perinatal mortality. Eclampsia cannot always be prevented. The likelihood of identifying a new case of proteinuric hypertension at any particular visit is very low using traditional antenatal care schedules, and care could be focused on women at higher risk. PMID- 1428650 TI - Staff competence and program compliance: Scotland. PMID- 1428651 TI - Blood pressure, growth retardation, and preterm delivery. AB - The effect of various levels of both diastolic and systolic blood pressure at various times during pregnancy on the rates of intrauterine growth retardation (IUGR) and preterm delivery (PTD) were determined. Low systolic and diastolic pressures were associated with both IUGR and PTD, as were high pressures. Low pressures tended to be associated with spontaneous preterm deliveries, whereas high pressures were associated with more indicated preterm deliveries. PMID- 1428652 TI - Smoking during pregnancy. Pregnancy risks and socio-demographic characteristics among pregnant smokers. AB - Maternal smoking during pregnancy is causally related to fetal growth retardation. Smoking more than doubles the risk for the birth of a small-for gestational-age infant. About 30% of the Swedish pregnant population smoke in early pregnancy. Despite that practically all pregnant women in Sweden today are aware of the hazards of smoking, about 70% of the smokers continue to smoke during pregnancy. Women who continue to smoke during pregnancy differ in terms of socio-demographic characteristics from those who stop smoking during pregnancy. PMID- 1428653 TI - Smoking during pregnancy. Possibilities of prevention in antenatal care. AB - Prevention of smoking in pregnancy is a mission of utmost importance since the fetal outcome is improved when the mother quits smoking. Methods to prevent smoking have to consider maternal attitudes and characteristics and be based on pedagogical and behavioral principles. A well-motivated staff, a self-help manual accepted by most women, and special support to those who want it are minimal requirements. PMID- 1428654 TI - Amsterdam: HIV nursing: caring for the future. PMID- 1428655 TI - The economics of AIDS. PMID- 1428656 TI - Few teens use condoms despite AIDS. PMID- 1428657 TI - Nurses respond to substance abuse. AB - Because of their close contact with the community, nurses are vital in caring for substance abusers and in preventing addiction. And their roles in community and national programmes in this area are increasing. Below, an overview of the problems associated with substance abuse and how nurses are needed to provide effective care, prevention and education. PMID- 1428658 TI - Development of a PHC nursing information system in Korea. AB - WHO has established collaborating centres at educational institutions throughout the world to assist with WHO research. In 1988 a WHO Collaborating Centre was inaugurated at Yonsei University College of Nursing in Korea. Since then two important research projects have been completed for establishing a data bank of human resources of nursing for primary health care (PHC) in Korea. Both projects strengthen the PHC nursing information systems in Korea and, as such, are beginning to develop PHC networks throughout Korea, passing on information to an international network system. Below, the rationale behind the two projects, the methodology and the results. PMID- 1428659 TI - Changing the image of nursing in Jordan through effective role negotiation. AB - As with other nurses worldwide, image, status and role definition are prominent issues in Jordan. Here nursing is considered menial work and the roles and responsibilities of the nurse have not yet been formally defined by royal decree, Jordanian courts or the nursing profession. Moreover, while nursing curricula ordinarily influence scope of practice, nurse educators have long noted an incongruity between nurses training and their roles in practice. Although Jordanian nurses are educated to be change agents, patient advocates, health educators and critical thinkers they function more like medical assistants and housekeepers. PMID- 1428660 TI - Higher education via satellite. AB - With the rapid advances in health, medical and technological fields, there is a pressing need for more nurses to obtain higher university degrees and continuing education in order to deliver quality care. Advanced education is necessary for not only nurse teachers but also clinical nurses. Yet access and familial duties often impede further study. Below, how Norwegian educational bodies solved the problem of reaching and teaching nurses throughout the country. PMID- 1428661 TI - Community and culture: a Chinese model of community care for the mentally ill. AB - Although psychiatric hospitals are thought to be the main focus of care for the mentally ill, China has not inherited the large asylums that were, and are, such a feature in the West. China has developed her own model of community care for the mentally ill, which is coherent with what are seen to be the available resources and fits into existing structures of social organisation. The elements in this model include small neighbourhood workstations, factory clinic liaison work, 'home beds' and neighbourhood care units. So far alternative accommodation schemes appear to have no part to play in the model. The reasons for this are discussed. However, while the Chinese model of community care for the mentally ill is quite well articulated, there appear to be major problems in ensuring its implementation. PMID- 1428662 TI - The community meeting: a review. AB - Community meetings are conducted in many psychiatric units and institutions. The formats, methods and theoretical backgrounds of the meetings however are very diversified. Most of the claims for beneficial effects are based on clinical impressions or indirect observations. The few structured studies that have been performed show that community meetings have the effect of reducing unfavorable ward incidents, especially aggressive ones. Much research remains to be done to confirm these findings and to elucidate the basic ingredients of the community meeting in providing beneficial effects. PMID- 1428663 TI - The 1983 Mental Health Act in five local authorities: a study of the practice of approved social workers. AB - This paper represents the first report of an ongoing collaborative project and charts the activities of social workers undertaking their duties within the framework of the 1983 Mental Health Act in five English Local Authorities for one year. Social workers are involved in a range of duties under the Act, but most commonly they are involved in assessments with a view to compulsory detention. The characteristics of people assessed are examined, and a profile emerges of vulnerable subgroups, typically younger men, older women, and people living in socially impoverished situations. Considerable variation between Authorities is found in terms of numbers of assessments, and in numbers of detentions. Low levels of 'diversion' into alternative care are identified. Comparisons are made with a major national study which took place four years earlier. Higher rates of detention are found on average, but lower rates of use of emergency provision (Section 4). An examination of the organisational context within which Approved Social Workers (ASWs) practice reveals a great deal of variation between authorities in terms of the ongoing experience of assessments available to ASWs. Social workers based in Emergency Duty Teams and Hospital Teams are compared, and a distinctive profile of their work emerges, the hospital-based ASWs being more likely to be assessing 'known' people, often already in hospital, and referred for assessment by consultants. The implications of these findings for the management and deployment of Approved Social Workers are briefly discussed. The emphasis is upon the role of the ASW in terms of balancing the rights and needs of people assessed under the Act. PMID- 1428664 TI - Counselor training as a treatment for alcoholism: the helper therapy principle in action. AB - Extensive harmful drinking of alcohol is a major problem for many groups of Australian Aborigines and western treatment approaches have had limited effect. In order to stress cultural factors in treatment, a program to train indigenous Aborigines as alcoholism counselors for their communities was developed. In its more than 10 years of existence 145 counselors have been graduated. Of those initially entering the two year program 60% have graduated. Most of those have found employment as alcohol counselors for their people, and the numbers of Aborigines treated has increased. About 90% of those who entered the training had severe repeated substance abuse disorders in their recent history. The training and the alcohol counseling employment appears to be highly associated with continuing sobriety. For those who graduated the program only 4.8% returned to drinking. Those who completed only the first phase, 8.4% returned to drinking. Of those who were terminated from the program, 74% returned to drinking. Training alcoholics as alcohol counselors appears to be associated with vocational success and maintenance of sobriety as predicted by Riessman's "helper-therapy principle." PMID- 1428665 TI - Assessment of life stress events: the etiology and measurement of traumatic stress disorder. AB - The impact of stressful life events on health has been of considerable interest from a cross-cultural perspective. Examined herein is the etiology and onset of post-traumatic stress disorder with careful review of the diagnostic criteria, current measures used and clinical dimensions of PTSD. Also examined from a cross cultural perspective is how psychological trauma may be processed by victims of trauma and subsequent approaches both pharmacological and psychotherapeutic to the treatment of post-traumatic stress disorder. PMID- 1428666 TI - The Arab nurse and the Jewish psychotic patient in the closed psychiatric ward. AB - The ongoing Israeli-Arab conflict has its impact on the mental health system. This issue is investigated from the point of view of the interactional process in the locked unit mainly between the Arab nurse and the Jewish psychotic patient. The unique experience of being treated by the formal enemy during one of the most vulnerable periods seems to be sometimes even therapeutic for the patient. Aspects concerning psychopathology, psychodynamics and social interaction are evaluated through observation and interviews with patients and staff members. Ways of dealing with the complicated issues are discussed. PMID- 1428668 TI - Molecular biology of receptors and transporters. Bacterial and glucose transporters. Introduction. PMID- 1428667 TI - The detection of psychiatric cases by Greek physicians: report on a study carried out in a Greek primary care setting. AB - The detection of psychiatric disorder by primary care physicians in Greece was investigated using four non-psychiatric physicians. The General Health Questionnaire indicated a high probable prevalence of psychiatric disorder (77.8%), but the physicians rated only 9.3% of the sample as cases. Eighty eight per cent of the probable cases were undetected by the doctors. The doctors' reporting of cases was not affected by the demographic characteristics of the sample and only weakly affected by the patients' total GHQ score. The high probable prevalence and low detection rate is a cause for concern and requires further investigation. PMID- 1428669 TI - Group translocation of glucose and other carbohydrates by the bacterial phosphotransferase system. PMID- 1428670 TI - Sugar-cation symport systems in bacteria. PMID- 1428672 TI - The insulin-sensitive glucose transporter. PMID- 1428671 TI - Molecular and cellular physiology of GLUT-2, a high-Km facilitated diffusion glucose transporter. PMID- 1428673 TI - Amino acid transport in bacteria. PMID- 1428674 TI - Cellular effects of early exposure to sex hormones and antihormones. PMID- 1428675 TI - The cell biology of pattern formation during Drosophila development. PMID- 1428676 TI - Assays of random motility of polymorphonuclear leukocytes in vitro. PMID- 1428677 TI - In search of molecular origins of cellular differentiation in Volvox and its relatives. PMID- 1428678 TI - Actin matrix of dendritic spines, synaptic plasticity, and long-term potentiation. PMID- 1428679 TI - Biogenesis of the vacuole in Saccharomyces cerevisiae. PMID- 1428680 TI - [Chronic renal failure]. PMID- 1428682 TI - [ACE inhibitors in hypertension and heart failure]. PMID- 1428681 TI - [Digitalis, catecholamines and vasodilators in heart failure]. PMID- 1428683 TI - [Diuretics. Range of effect, indications and therapeutic results in heart diseases]. PMID- 1428684 TI - [Immunosuppressive therapy in myocarditis and dilated cardiomyopathy?]. PMID- 1428685 TI - [Thrombocyte aggregation inhibitors, anticoagulants and thrombolytic agents in heart diseases]. PMID- 1428686 TI - [Recent progress regarding nitrates and their use in stable and unstable angina pectoris, pre-infarction syndrome and myocardial infarct]. PMID- 1428687 TI - [Chilblain lupus erythematosus. A case report]. PMID- 1428688 TI - [Moxonidine. A new centrally active antihypertensive drug]. PMID- 1428689 TI - [Diuretics and tubuloglomerular feedback]. PMID- 1428690 TI - [Profile of the action of diuretics. Piretanide in comparison with thiazides and anti-kaliuretic drugs]. PMID- 1428691 TI - [Renal effects of piretanide]. PMID- 1428692 TI - [Determination of glomerular filtration rate in man using single shot piracetam clearance]. PMID- 1428693 TI - [Hypertension as a risk factor for progression of renal failure]. PMID- 1428694 TI - [Diuretic therapy in moderate and advanced renal failure]. PMID- 1428696 TI - [Pharmacodynamics of piretanide in compromised kidney function. Dose response relationship and equipotency with furosemide]. PMID- 1428695 TI - [Piretanide. Effect on renal hemodynamics, its hormonal regulation and renal prostaglandin metabolism in pre-terminal renal failure]. PMID- 1428698 TI - [Progression of renal dysfunction. Possibilities of nephroprotection with ACE inhibitors]. PMID- 1428697 TI - [Clinical and pathophysiologic effects of piretanide in nephrotic syndrome]. PMID- 1428699 TI - [Future aspects of therapy with diuretics]. PMID- 1428700 TI - [Effect of piretanide on disorders of kidney function in kidney transplantation. A pilot project]. PMID- 1428701 TI - Radial keratotomy. 1. The wound healing process and measurement of incisional gape in two animal models using in vivo confocal microscopy. AB - Using in vivo confocal microscopy, corneal wound healing was evaluated in both rabbit and cat eyes after radial keratotomy. A total of six rabbit and six cat eyes were evaluated sequentially over time for 1 mo after surgery by in vivo confocal microscopy, and quantitative measurements of changes in incisional wound gape were determined. In vivo histopathologic changes were correlated with conventional histopathologic findings in 18 rabbit and 4 cat eyes; the animals were killed at various intervals from 0-30 days after surgery. In the rabbit, in vivo corneal wound healing was characterized by the initial ingrowth of corneal epithelium followed by persistence within the wound without a marked fibrotic response. Measurement of incisional wound gape showed increasing gape from 144 +/ 32 microns on day 0 to 976 +/- 155 microns on day 26 at a distance of 2.4 mm from the optical zone. These in vivo measurements were not significantly different (P = 0.996) from those obtained using conventional histopathologic techniques which showed an incisional wound gape of 252 +/- 112 microns on day 0 and 917 +/- 216 microns on day 26 at 2.5 mm from the optical zone. In the cat eyes, healing of radial keratotomy wounds showed an initial increase in incisional wound gape from 135 +/- 56 microns on day 0 to 245 +/- 88 microns on day 7 at a distance of 2.4 mm from the optical zone. Starting at day 14 and continuing to day 30, there was a progressive decrease in incisional wound gape from 198 +/- 41 microns to 92 +/- 35 microns. Sequential, in vivo histopathologic analyses indicated that increasing incisional wound gape correlated with the retention of corneal epithelium in the wound. Initiation of decreasing incisional wound gape was associated with replacement of the incisional epithelial plug with fibroblastic tissue. These changes in the incisional wound gape observed in the cat suggest that healing of radial keratotomy wounds involves contraction of the wound in response to the ingrowth of fibroblastic cells. Furthermore, the contractile response appears to be biphasic involving a precontractile and contractile phase. Overall these data indicated that in vivo confocal microscopy provides quantitative histopathologic data on living tissue comparable with that obtained with conventional techniques on dead, fixed, and sectioned tissue. Additionally, the absence of wound fibrosis in the rabbit radial keratotomy model raises important questions as to the appropriateness of this experimental model for human radial keratotomy. PMID- 1428702 TI - Radial keratotomy. II. Role of the myofibroblast in corneal wound contraction. AB - The cellular mechanism of corneal wound contraction after radial keratotomy (RK) was studied in a feline eye model. A total of 10 cat eyes were evaluated at various times from 0-30 days after surgery. Changes in the distribution of intracellular filamentous actin, nonmuscle myosin, alpha-actinin, surface membrane alpha 5 beta 1 integrin, and extracellular fibronectin were studied using immunofluorescence and laser confocal and electron microscopy. From day 3 7, staining for fibronectin increased along the wound margin. By day 7, keratocytes adjacent to the wound margin showed increased f-actin staining with intense staining for fibronectin compared with normal keratocytes. Myosin and alpha 5 beta 1 integrin expression was very weak at this time; alpha-actinin was not found. By day 14, fibroblasts within the wound formed f-actin microfilament bundles (stress fibers) which colocalized with fibronectin. Wound-healing fibroblasts also stained positively for alpha 5 beta 1 integrin, myosin, and alpha-actinin (the latter two were colocalized). The presence of myosin and alpha actinin in the wound fibroblasts and the re-organization of f-actin into stress fibers by day 14 correlated with the development of wound contraction. A comparison of the cellular distribution of actin, myosin, and alpha-actinin with alpha 5 beta 1 integrin 14 days after injury suggested that integrin was localized along stress fiber bundles during wound contraction. The data from this study suggest that modulation of wound gape during healing of RK wounds may involve transformation of the corneal keratocyte to a myofibroblast-like cell and the subsequent formation of intracellular stress fibers composed of f-actin, nonmuscle myosin, and alpha-actinin. Based on the colocalization of fibronectin filaments and f-actin filaments and the unique distribution of alpha 5 beta 1 integrin, these findings support the hypothesis that the tension within the wound is generated by the formation of intracellular stress fibers and the interactions between stress fibers and the extracellular matrix, mediated by specific membrane receptor molecules. PMID- 1428703 TI - Radial keratotomy. III. Relationship between wound gape and corneal curvature in primate eyes. AB - The relationship between changes in wound gape and corneal curvature after radial keratotomy (RK) was evaluated in five primates. Four-incision RK was performed using a diamond knife set to 100% of central corneal thickness with a 3-mm optical zone. In vivo measurements of wound gape were obtained using tandem scanning confocal microscopy at 3, 7, 14, and 45 days after surgery. The changes in corneal contour were measured at the same time points using a corneal modeling system with a specially designed primate cone. Wounds progressively increased in width to a maximum of 38 +/- 1 microns (n = 5) at day 7. After day 7, wounds showed increasing fibrosis which correlated with decreasing wound gape to 20 +/- 1 microns at day 45. A similar temporal change was detected in central corneal curvature (K), with maximum flattening occurring at day 7 (delta K = -3.17 +/- 0.90 diopters, n = 5), and progressive regression of effect to -1.32 +/- 0.61 diopters (n = 5) at day 45. Although there was interanimal variation, the mean temporal changes in corneal curvature significantly paralleled the changes in wound gape (r = -0.96, n = 4, P < 0.05). Based upon these findings, a simple geometric model was proposed which provides a hypothetic foundation for the relationship between corneal curvature and wound gape after RK. Calculations of wound gape made from this analytic model (using the measured topographic data) showed significant correlation with the actual wound gape measurements (r = 0.96, n = 4, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428704 TI - Effects of epidermal growth factor, fibroblast growth factor, and transforming growth factor-beta on corneal cell chemotaxis. AB - The effects of recombinant basic fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor-beta (TGF-beta) on migration of human and bovine corneal cells were determined using checkerboard analysis in Boyden chambers. EGF, FGF, and TGF-beta each stimulated high levels of chemotactic migration. Each growth factor, however, induced a different dose response pattern. Migration stimulated by FGF reached a plateau at a concentration between 100 and 200 ng/ml for endothelial, epithelial, and stromal fibroblasts. By contrast, chemotactic responses to EGF peaked between 10 and 50 ng/ml, then decreased at higher concentrations. TGF-beta also stimulated a peak in migration in all three corneal cells, but the peak of migration occurred at an approximately 1000-fold lower concentration (1 pg/ml) than for EGF. Checkerboard analysis demonstrated that FGF and EGF, but not TGF-beta, stimulated chemokinesis of bovine, stromal, and endothelial cells. These results demonstrate that FGF, EGF, and TGF-beta induce migration in pure populations of bovine and human corneal cells and support the concept that these growth factors may play key roles in corneal wound healing by regulating migration of corneal cells. PMID- 1428706 TI - Fos expression and growth regulation in bovine corneal endothelial cells. AB - The authors evaluated the effects of stimulation (by serum, wounding, and three peptide growth factors: fibroblast growth factor [FGF], insulin, and transforming growth factor-beta [TGF-beta 1]) on the expression of the protein product of the immediate early gene, c-fos in bovine corneal endothelial (BCE) cells. These results were compared with those of cells which were made quiescent by serum starvation. They also examined the effect of these same growth factors or wounding on DNA synthesis. Quiescent cells expressed low levels of c-fos protein. Serum was the most potent stimulator, whereas FGF and insulin were modest stimulators. TGF-beta 1 did not significantly stimulate c-fos protein production. The results from DNA synthesis were different. Serum and FGF were still the most potent stimulators; insulin and TGF-beta 1 were weak stimulators. These data suggest that growth factors induce c-fos protein in BCE cells and that this may in part regulate the downstream event, cellular proliferation. Further investigation into the regulation of this and other protooncogene products may provide insight into the mechanisms which modulate corneal endothelial cell growth in humans. PMID- 1428705 TI - Detection of transforming growth factor-alpha messenger RNA and protein in human corneal epithelial cells. AB - Human corneal epithelial cells are normally shed from the apical surface and replaced primarily by mitosis of basal cells. Growth factors may regulate this process, but the sources for the growth factors have not been fully established. One potential source for growth factors is tear fluid, and epidermal growth factor (EGF) has been detected in the lacrimal gland and in tears. However, the hydrophilic structure and size of growth factors such as EGF may limit penetration to basal layers of intact epithelium. It is possible that turnover of basal human corneal epithelial cells might be regulated by growth factors acting by an autocrine mechanism. To determine if human corneal epithelial cells synthesize a potential autocrine growth factor, the authors analyzed human corneal epithelial cells for transforming growth factor-alpha (TGF-alpha) messenger RNA and protein, a growth factor that is structurally related to EGF and binds to the EGF receptor. Radioimmunoassay of human corneal epithelial cell cultures detected substantial levels of immunoreactive TGF-alpha (3 ng/10(6) cells). Immunohistochemical staining of human corneas also revealed the presence of immunoreactive TGF-alpha in the corneal epithelium. Northern hybridization with a 32P-labeled complementary DNA probe for TGF-alpha generated a single intense band at 4.4 kilobases, indicating the presence of TGF-alpha messenger RNA in cultured human corneal epithelial cells. These results support the hypothesis that normal turnover of corneal epithelium is controlled by the autocrine production of growth factors, such as TGF-alpha. Growth factors present in tears may function primarily as exocrine factors to stimulate healing of epithelial injuries after the epithelial barrier has been damaged. PMID- 1428707 TI - Metabolic and morphologic changes in the corneal endothelium. The effects of potassium cyanide, iodoacetamide, and ouabain. AB - The metabolic pathways of glycolysis and mitochondrial respiration in the corneal endothelial cell are the primary sources of the adenosine triphosphate (ATP) necessary to maintain endothelial structure and pump fluid to maintain the corneal stroma in its normally dehydrated and transparent state. The correlation between endothelial metabolism and morphology in rabbits was studied for 7 days after the application of three different agents: (1) iodoacetamide, used to inhibit ATP synthesis from both glycolysis and respiration; (2) potassium cyanide (KCN), used to inhibit ATP synthesis from respiration only; and (3) ouabain, used to inhibit fluid pumping but not ATP synthesis. After application of each of these three drugs to the corneal endothelium, changes in endothelial morphology were measured. The greatest change resulted from the use of iodoacetamide. Specular microscopic examination of the endothelium after the application of iodoacetamide showed progressive degradation of the integrity of the cellular structure; after 6 hr, there were no discernible cell borders. In those corneas treated with either KCN or ouabain, only minor changes in the endothelium were seen during the full 7 days of the investigation. Computer-assisted morphometric analysis showed an increase in the coefficient of variation of both cell area and perimeter in all cases. This increase was greater in the corneas treated with ouabain than those treated with either iodoacetamide or KCN. Redox fluorometry showed that the metabolic ratio (autofluorescence of reduced pyridine nucleotides divided by that of oxidized flavoproteins) decreased significantly in the iodoacetamide-treated corneas, increased significantly in the KCN group, and showed no significant change in the corneas in the ouabain group, all compared with a control group. The results showed that (1) when ATP produced by both glycolysis and respiration was inhibited by 0.1 mmol/l iodoacetamide, the endothelial cells could not survive, but (2) when ATP synthesis produced by respiration alone was inhibited by 1.0 mmol/l KCN, the cells could survive for at least 1 wk on the ATP produced by anaerobic glycolysis. Furthermore, the polymegathism seen after application of ouabain, a drug that is not believed to affect ATP synthesis but inhibits the endothelial pump function, is greater than that seen as a result of reduced pump function caused by inhibited respiration produced by 1.0 mmol/l KCN. Combining specular microscopy, computer-assisted morphometric analysis, redox fluorometry, and corneal pachymetry allowed correlations between corneal endothelial metabolism, pump function, and morphology to be studied. PMID- 1428708 TI - Comparison of external and internal approaches for transplantation of autologous retinal pigment epithelium. AB - The feasibility of autologous transplantation of retinal pigment epithelial (RPE) cells from just posterior to the ora serrata to the posterior pole was demonstrated in the rabbit model. Two techniques for introducing the transplanted cells were compared: an internal (anterior transvitreal) and an external (posterior transscleral) penetration to the subretinal space. In both approaches, RPE cells were obtained by biopsy from the peripheral retina of a rabbit eye, cultured, labeled with a fluorescent dye and 3H-thymidine, and transplanted to the posterior pole of the same or contralateral eye. The external approach consistently resulted in a greater number of transplanted cells on Bruch's membrane. The internal technique was more precise because it permitted direct visualization of the placement of the transplanted RPE. Transplantation of autologous RPE is a possibility that should be further pursued. PMID- 1428709 TI - Morphologic comparisons between rhodopsin-mediated and short-wavelength classes of retinal light damage. AB - The histologic manifestations of rhodopsin-mediated versus short-wavelength classes of retinal phototoxicity were compared after spectral exposures of the albino rat retina. Animals were exposed to wave-bands of light centered at the peak of rhodopsin absorbance (green, 500 nm) or in the ultraviolet A (UVA; 360 nm). Intensity-damage curves generated for each wave-band indicated that UVA light was 50-80 times more effective than green light at causing photoreceptor cell losses. Examination of early ultrastructural changes in rod inner segments, outer segments, and retinal pigment epithelium revealed a remarkable degree of similarity between UVA and green light-induced damage. Furthermore, the two classes of damage were indistinguishable in terms of post-exposure recovery from threshold damage and regional distribution of photoreceptor cell loss along the vertical meridian. The finding of essentially identical histologic manifestations for the two classes of damage raises the possibility that they share a common biochemical etiology or pathway of cell destruction. PMID- 1428710 TI - Dissociation between prostaglandin levels and blood flow to the retina and choroid in the newborn pig after nonsteroidal antiinflammatory drugs. AB - To assess whether prostaglandins contribute to the control of basal retinal and choroidal hemodynamics, retinal (RBF) and choroidal blood flow (ChBF) were measured by a microsphere technique in 1- to 4-day-old pigs before and after (at 20 and 60 min) administration of indomethacin (0.3 mg/kg, n = 6 or 10 mg/kg, n = 5), ibuprofen (40 mg/kg, n = 7), naproxen (20 mg/kg, n = 5) or vehicle (n = 8). In 40 other animals, PGF2 alpha, PGE2, and 6-keto-PGF1 alpha were measured in the retina and choroid at times corresponding to blood flow measurements. Mean arterial blood pressure and blood gases and pH were not altered by any of the agents. Except for the lower dose of indomethacin (0.3 mg/kg), which did not change retinal and choroidal prostaglandin concentrations, the prostaglandin levels were decreased similarly (P < 0.01) by the three drugs. However, RBF and ChBF were not changed by ibuprofen and naproxen, but decreased to the same extent after low and high doses of indomethacin. The data suggest that the effects of indomethacin on RBF and ChBF cannot be simply attributed to prostaglandin synthesis inhibition, and that prostaglandins may not play a significant role in controlling basal blood flow to the retina and choroid. PMID- 1428711 TI - Blood-retinal barrier dysfunction at the pigment epithelium induced by blue light. AB - Exposure to low-intensity white light can induce dysfunction of the blood-retinal barrier (BRB) at the retinal pigment epithelium (RPE). To determine whether the shorter wavelengths white light are responsible for this dysfunction, rabbit retinas were exposed to blue light (400-520 nm) or yellow light (510-740 nm). The permeability of the BRB, a parameter for the integrity of the barrier, was quantified with vitreous fluorophotometry. Morphologically, the barrier at the RPE was visualized on light and electron microscopy using horseradish peroxidase (HRP) as a tracer. Seventeen pigmented rabbits were exposed to blue light and 11 were exposed to yellow light. Vitreous fluorescein leakage increased with the exposure energy according to a power function (correlation coefficient > 0.79). The threshold energy for an increase in BRB permeability was 50 J/cm2 (0.014 W/cm2 for 1 hr) after blue and 1600 J/cm2 after yellow light. HRP tracing demonstrated that after blue light exposure, a significant fluorescein leakage on fluorophotometry corresponded to the presence of HRP in the RPE cells and in the subretinal space. After yellow light exposures of < 3700 J/cm2 and in rabbits with no significant fluorescein leakage, the HRP was limited to the choroidal capillaries and Bruch's membrane. These results demonstrate that the blue component of white light causes dysfunction of the BRB at the RPE 30 times more effectively than the longer wavelength fraction of white light. As a result, a blue light blocking filter should be used in ocular surgery on humans when an operating microscope is being used (light power 0.1-0.9 W/cm2). PMID- 1428712 TI - Retinal pigment epithelium-stromal interactions modulate hyaluronic acid deposition. AB - Hyaluronic acid (HA) is a major component of the extracellular matrix (ECM) and is particularly prominent in various structures of the eye. Choroidal mesenchymal fibroblasts (CHM) and fetal retinal pigment epithelial (fRPE) cells were cultured individually and in cocultivation, as a paradigm for ocular stromal-epithelial interactions. Such interactions are thought to be a key mechanism for the modulation of the ECM and of HA deposition in the region of Bruch's membrane and related structures. In cocultivation, increased levels of HA production were observed, more than the sum of the two cell types grown individually. Conditioned medium from fRPE cultures placed over CHM cells was able to enhance production in such cells several-fold, demonstrating that cell-cell contact was not needed for this enhanced production. On the other hand, when conditioned medium from CHM fibroblasts was added to the fetal RPE cells, no increase in HA production was observed. A soluble HA-stimulating factor apparently released by fRPE cells in a paracrine manner enhanced HA production in CHM cells. The fRPE cell-conditioned media was unable to exert this effect on the fRPE cells themselves. The fRPE cells may lack the appropriate receptor. Alternatively, they may not have the biosynthetic machinery for augmented HA production. PMID- 1428713 TI - Grating, vernier, and letter acuity in retinitis pigmentosa. AB - Grating, vernier, and letter acuities were compared in 25 patients with retinitis pigmentosa (RP), whose Snellen visual acuities were better than 20/40, to address the mechanism of visual acuity loss. For these patients with RP, all three types of visual acuity were reduced to an equivalent degree from those of a control group of 10 age-similar, visually normal subjects. The findings indicate that the visual acuity losses of these subjects with RP did not result from cone spatial undersampling (due, for example, to a random loss of foveal cones), from cone sampling irregularities (due to random alterations in foveal cone position), or from a selective loss of sensitivity to high spatial frequencies (as might result from changes in media transmission characteristics or a gain reduction in high spatial frequency mechanisms). In addition, previous studies have indicated that acuity losses in such patients with RP do not result from reductions in the quantum-catching ability of foveal cones. The most likely explanation for the equivalent losses in all three acuity types in these patients with RP appears to be an alteration in foveal spatial scale, consistent with a generalized increase in foveal intercone spacing. PMID- 1428714 TI - In vitro studies of the contractility of cell types involved in proliferative vitreoretinopathy. AB - The contractile activity of cells in epiretinal membranes leads to retinal detachment and proliferative vitreoretinopathy, but it is unknown which cell type contributes most to this process. In this study, the relative contractility of three cell types thought to be involved in epiretinal membrane formation was measured. Bovine scleral fibroblasts (BSF), retinal pigment epithelium (BRPE) and retinal glia (BRG) were suspended in a rapidly polymerizing floating type I collagen matrix. Matrix contraction was assessed and morphologic studies were performed using light microscopy and scanning electron microscopy. BSF reached 50% contraction within 4 days and BRPE needed 7-10 days, whereas BRG showed no matrix contraction. Cell proliferation, as shown by bromodeoxyuridine labeling, did not occur in the matrix. During the period of greatest contraction, cells had formed processes but were isolated from each other. Over the 7 day period, an increasing number of cells was found on the surface of the matrix, resulting (with BSF) in an encapsulating monolayer. This monolayer developed only after most of the contraction was over. These findings suggest that BSF and BRPE reorganize the collagen matrix through a combination of individual cellular mobility and attachment to the collagen fibers. BRG's inability to attach to the collagen and reorganize its arrangement resulted in its lack of matrix contraction. PMID- 1428715 TI - Proteins of the vitreous humor during experimentally induced myopia. AB - Significant myopia was evident within 14 days after a translucent goggle was placed over the eye of a newly hatched chick. This myopia was characterized by large negative refractive error, increased axial and equatorial eye lengths, and increased wet eye weight. The volume of the vitreous humor increased in the myopic eye, because of a signficant accumulation of liquid vitreous humor. The protein concentration of the vitreous humor of the myopic and nonmyopic eyes was greater at day 14 than at day 0 (ie, first day after hatching). Moreover, over this time, the protein concentration in the liquid component decreased, whereas the protein concentration in the gel component increased in both myopic and nonmyopic eyes. No difference was found in the protein concentrations between the myopic and nonmyopic eye at day 14. Polyacrylamide gel electrophoresis revealed changes in band position and intensity of individual protein compoents between days 0 and 14. No major differences were found in the gel or the liquid vitreous humor between the myopic and the nonmyopic eyes. Comparison of vitreous humor proteins with proteins from the plasma showed that some but not all of the proteins in the vitreous had the same apparent molecular masses as proteins from these sources. PMID- 1428716 TI - Subconjunctival sustained release 5-fluorouracil. AB - The authors have developed a sustained release device for 5-fluorouracil (5-FU) made up of a 12 mg pellet of drug coated in a mixture of permeable and impermeable polymers. When implanted subconjunctivally in rabbits, these devices released 5-FU at approximately 1 mg/d for over 10 days. Devices were implanted into four cynomolgus monkey eyes after posterior lip sclerotomy. One eye (treatment) received a device that contained 12 mg 5-FU and the other eye (control) received a placebo device that contained no drug. In control eyes, intraocular pressures returned to normal within 1 wk. In treatment eyes, pressures remained significantly lower throughout the experimental period (3 mo). There was no indication of impaired wound healing, corneal toxicity, inflammation, or damage to the ciliary body in rabbits or monkeys. PMID- 1428717 TI - Injectable microspheres with controlled drug release for glaucoma filtering surgery. AB - The authors evaluated the effects of biodegradable poly (lactic acid) microspheres that provided the controlled release of the antimetabolic agent adriamycin (ADR) to prevent post surgical fibrosis after glaucoma filtering surgery. Fifty six eyes of 28 rabbits underwent posterior lip sclerotomy and received a 0.2 ml subconjunctival injection that contained microspheres 90 degrees from the filtering site immediately after surgery. Microspheres containing ADR (100 or 200 micrograms) were randomly administered to one eye. The fellow eyes served as controls and received microspheres without the drug. Intraocular pressure in the eyes treated with the microspheres that contained the drug was significantly lower than that in the control eyes from days 7-12 in the 100 micrograms group and from days 6-16 in the 200 micrograms group (P < .05). Eyes that received ADR had a significantly longer patent filtering bleb compared with the control eyes (P < .05). No corneal complications were observed in the eyes treated with 100 micrograms of ADR and the control eyes. Peripheral corneal opacities (25%) and epithelial erosion (17%) were observed in the eyes that received the 200 micrograms dose, but the cornea returned to normal after 4 wk. These results suggest that controlled-drug-release microspheres with an antimetabolic agent may be promising for preventing fibrosis after surgery. PMID- 1428718 TI - Basal tear turnover and topical timolol in glaucoma patients and healthy controls by fluorophotometry. AB - To assess the effect of glaucoma and timolol on tear secretion, basal tear turnover was measured with fluorophotometry in 13 open-angle glaucoma patients not using any ophthalmic medication, 24 patients using timolol medication daily, and 41 healthy control subjects. Basal tear turnover is defined as the tear turnover at the lowest level of reflex lacrimation possible under physiologic conditions. Tear turnover was calculated from the decay of the tear fluorescence after instillation of fluorescein. Minimal influence of reflex lacrimation was obtained by instilling 1 microliter of 2% fluorescein without touching the eye and by discarding measurements performed in the first 5 min. Minimization was confirmed by a monophasic decay of tear fluorescence. The values of patients who used timolol and those who did not use timolol were significantly lower than those of healthy control subjects (mean values in percent/minute +/- standard deviation: 10.1 +/- 3.2, 12.3 +/- 4.1, and 15.6 +/- 5.4, respectively; Student's t-test: P < 0.02). The values of patients who used timolol were significantly lower compared to those of patients who did not use timolol (P = 0.03). The tear film break up time values of patients who used timolol were significantly shorter than those of patients who did not use timolol and healthy control subjects (Fisher exact test: P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428719 TI - Identification and quantification of transferrin receptors on trabecular cells. AB - The authors identified and quantified the receptor for transferrin on trabecular meshwork (TM) cells cultured from porcine eyes by using two receptor assays. Flow cytometric analysis of TM cells that were incubated with a monoclonal antibody to the transferrin receptor revealed such receptors, which decreased in number as the cells passed from the pre- to the post-confluent phase. Quantitative characterization by radioligand binding of 125I-transferrin to trabecular cells followed by Scatchard analysis showed that pre-confluent cultures expressed 23,839 +/- 6746 high-affinity receptors/cell and post-confluent cultures expressed 5104 +/- 3639 receptors/cell. The expression of the receptor for transferrin reflects the index of mitotic activity and can be correlated with the proliferative state of the trabecular cells. Further characterization of the receptors for transferrin in the TM may open up the possibility of a pharmacologic approach that enhances the TM cell population, which is known to decrease with age and in glaucomatous states of the eye. PMID- 1428720 TI - Reducing intraocular pressure by intubation elicits precocious development and innervation of the embryonic chick cornea. AB - Growth of the embryonic chick cornea was directly related to, and coordinated with, overall eye growth. During normal development, the size of the embryonic chick cornea increased in three linear phases of diametric growth. Corneal diameter increased at a rate of 216 microns per day between embryonic day 4 (E4) and E7, 511 microns per day between E7 and E10, and 144 microns per day from E10 until after hatching. After the sustained release of intraocular pressure by intubation on E4, corneal diametric growth was reduced to a single phase of 122 microns per day. After intubation on E4, the mesenchyme surrounding the developing cornea was substantially thicker and the neural crest-derived corneal endothelium was established earlier. The primary corneal stroma of the intubated eye swelled and was precociously populated by neural crest-derived corneal fibroblasts. Thus, the timing of arrival of neural crest cells in the anterior segment and their contribution to the cornea were determined by the growth rate of the eye. Although the diameter of the cornea was substantially reduced after intubation, it was more densely populated by fibroblasts, resulting in a cornea that was substantially thicker than the control by E14. Prospective corneal nerves normally extend into the cornea proper on E11, concomitant with a decrease in its diametric growth rate. After intubation on E4, the perilimbal nerve ring was virtually complete by E5 and numerous nerves had extended throughout the E8 cornea. By E16, the cornea from the intubated eye contained a very high density of nerve fibers, possibly reflecting its reduced size. These data suggest that the primary corneal stroma does not permit nerve fiber extension and demonstrate that the timing of nerve fiber extension into the secondary corneal stroma is specified by the rate of oppositional diametric growth of the cornea. PMID- 1428721 TI - Interferon-gamma inhibits collagen synthesis by human tenon's capsule fibroblasts in vitro. PMID- 1428722 TI - Circadian rhythm in physiology and pharmacology. PMID- 1428723 TI - In vitro and in vivo circumvention of multidrug resistance by Servier 9788, a novel triazinoaminopiperidine derivative. AB - S 9788 is a novel triazinoaminopiperidine derivative which does not belong to any of the classes of compounds known to reverse multidrug resistance (MDR). S 9788 was far more potent than verapamil (VRP) in reversing resistance to adriamycin (ADR) in the ADR-selected murine leukaemia cell lines P388/ADR-1 and P388/ADR-10, and the human chronic myelogenous leukaemia K562/R. Fold reversion with S 9788 (5 microM) was, respectively, 3.5, 5.4 and 11.3 times greater than that with VRP (5 microM). S 9788 was also a more potent reversant of ADR resistance in the intrinsically resistant human colon adenocarcinoma COLO 320DM (2.3 fold), and of vincristine (VCR) resistance in the human MDR1 gene-transfected squamous lung carcinoma line S1/tMDR1 (5.6 fold). The activity of S 9788 depended on both the MDR cell line and the cytotoxic agent. S 9788 (50-100 mg/kg/d) administered IP once a day on days 1-4 resulted in a dose-dependent increase in the chemotherapeutic effect of VCR (0.25 mg/kg/d) in P388/VCR - bearing mice and ADR (4 mg/kg/d) in P388/ADR - bearing mice. Increases in antitumor activity were (% T/C) of +20-34% in the P388/ADR model and + 50-78% in the P388/VCR model with respect to cytotoxic agent treatment alone. S 9788 appeared to be devoid of toxicity at its effective doses. The mechanism of action of S 9788 is unknown but S 9788 (0.5-10 microM) induced a dose-dependent increase in ADR accumulation in KB-Al cells and compared to verapamil its effect was twice as active and approximately seven times more potent. We conclude that S 9788 is a novel agent capable of reversing MDR in vitro and in vivo, and whose pharmacological profile warrants its selection as a candidate drug for eventual assessment in the clinic. PMID- 1428724 TI - Pharmacokinetics and cytotoxicity of B.3839, a molecular combination of 5 fluorouracil and N-(2-chloroethyl)-N-nitrosourea, in a mouse model. AB - B.3839 is the prototype compound in a series of novel molecular combinations of chloroethylnitrosoureas and 5-fluorouracil(5-FU) and has been tested against MAC tumours in mice. Previous studies have shown it is moderately active against MAC15A and highly active against MAC13 though this activity is dependent on route of administration. The aim of this study was to determine whether bioavailability could explain this difference in anti-tumour activity. Plasma levels of B.3839 and 5-FU after i.p. and oral administration were measured using HPLC. Non tumour bearing and MAC26 bearing mice gave almost identical plasma profiles after i.p. administration with the Cmax being 29.8 and 30.4 micrograms ml-1 and t1/2 16 and 15 min. The AUCs were 15.3 and 13.9 micrograms h ml-1 suggesting tumour load had no influence over plasma levels. Oral administration gave a much lower Cmax of 8.0 micrograms ml-1 but an AUC of 15.2 micrograms h ml-1 due to a longer terminal t1/2 (94 min) giving 99% bioavailability. Levels of 5-FU release from B.3839 by either route were considered too small to influence anti-tumour activity. Cytotoxicity assays in vitro against the MAC lines gave IC70 values of 5.3, 13.8 and 8.6 micrograms ml-1 for MAC 26, 13 and 15A respectively after a one hour exposure. Bone marrow toxicity was shown to be less severe than that of TCNU which is currently in clinical trials. The results show bioavailability alone is not enough to explain tumour response. There appears to be a need for a threshold concentration (C) to be maintained for a period of time (t). PMID- 1428725 TI - Comparison of N-acetylcysteine and mesna as uroprotectors with ifosfamide combination chemotherapy in refractory germ cell tumors. AB - From January 1983 through August 1988, 318 consecutive patients with refractory germ cell neoplasms were treated with ifosfamide-containing combination chemotherapy. The patients received ifosfamide at 1.2 gm/m2/day with cis-platin 20 mg/m2/day for 5 days and etoposide 75 mg/m2/day for 5 days or vinblastine 0.11 mg/kg on days 1 and 2 for each cycle. Of 277 evaluable patients, NAC was used as an uroprotector in the initial 86 patients while the latter 191 consecutive patients received mesna to reduce urothelial toxicity. Dosages of NAC was 2.0 gm po q 6 hr and for mesna 120 mg/m2 IV push prior to ifosfamide and then 1200 mg/m2/day as continuous infusion of 5 consecutive days. All patients received 3.0 liters of normal saline per day. The number of courses of chemotherapy given in the two groups were similar. Twenty-four of the 86 patients (27.9%) receiving NAC developed hematuria (13 patients - grade 1, 4 patients - grade 2, and 7 patients grade 3 toxicity). While 8 out of 191 (4.2%) mesna patients developed hematuria (6 - grade 1 and 2 - grade 3) (p < 0.0001). The incidence of severity of renal toxicity was similar in the two groups. Ifosfamide dosage was reduced solely for urothelial toxicity in 11 patients receiving NAC compared with none of the patients receiving mesna (p < 0.0001). Chemotherapy response was similar in the two groups. In conclusion, mesna provides better urothelial protection from ifosfamide-induced toxicity than NAC and allows better maintenance of the drug dosage. PMID- 1428726 TI - Difluorodeoxycytidine (dFdC)--gemcitabine: a phase I study. AB - Difluorodeoxycytidine (dFdC) demonstrated broad spectrum activity in preclinical models. A phase 1 study utilizing twice weekly injections was conducted in 50 eligible and evaluable patients. Twenty-nine patients received drug by 30 minute infusion at doses of 5-90 mg/m2 and 22, by 5 minute bolus at 30-150 mg/m2. The primary dose limiting toxicities were marrow suppression and flu-like symptomatology. Thrombocytopenia was dose limiting at 75 mg/m2 on the infusion schedule and 150 mg/m2 on the 5 minute schedule. Flu-like symptoms with fever, rigors and malaise occurred the day of injection in many patients. One patient with renal cell carcinoma attained a partial response. Evaluation of the drug's efficacy and schedule dependency continue. PMID- 1428727 TI - Phase I study of mitonafide in solid tumors. AB - Mitonafide was the first synthetized compound of a new series of 3 nitronaphthalimides with intercalative properties. A phase I study with a conventional escalation scheme was developed. The schedule of drug administration was a daily x 5 days by short (1 h) intravenous (i.v.) infusion, every 21 days. Thirty evaluable patients were treated at doses from 15.4 mg/m2/d x 5 days to 138.6 mg/m2/d x 5 days. The study was interrupted due to appearance of central nervous system toxicity in 5 patients treated at doses above 118 mg/m2 x 5 days. This toxicity consisted firstly of loss of memory in all patients. It was irreversible and progressed in 3 patients to disorientation and confusion, leading to dementia in one of them. This was considered to be dose-limiting toxicity, and since it appeared to be related to the administration schedule, no further studies with short i.v. infusions of mitonafide are recommended. A phase I study utilizing a more desirable administration schedule over longer periods of time is ongoing in other centers. PMID- 1428728 TI - A phase I pharmacokinetic study of recombinant human tumor necrosis factor administered by a 5-day continuous infusion. AB - Nineteen patients with advanced cancer were entered into a phase I clinical trial of Tumor Necrosis Factor (TNF) which was designed to determine the pharmacokinetic profile, safety, and maximal tolerated dose (MTD) of the recombinant human cytokine in vivo. TNF was administered by continuous infusion for 24 hours followed by pharmacokinetics and a 120-hour infusion repeated every 3 weeks. The initial dose was 40 micrograms/m2 and was ultimately escalated to 200 micrograms/m2. A total of forty 5-day cycles were administered to 18 of these patients; and all were evaluable for toxicity. Toxicities in this trial included fever, chills, rigors, hypotension, headaches, seizures, lethargy, weight loss, and malaise. At all dose levels, but more significantly at the highest doses, hematological toxicities were observed and grade 3 neurotoxicity (headache and confusion), and hypotension were noted. Two patients expired during the study, and this was felt to be related to septic episodes. Because of these severe toxicities, 160 micrograms/m2 was defined as the MTD. At 160 micrograms/m2 peak serum levels occurred within 5-20 minutes of initiation and were not detectable 1 hour later. No anti-tumor responses were observed. No measurable plasma levels of TNF were observed with the administration of doses of 80 micrograms/m2. This dose level could be further studied in phase II studies alone and in combination with other agents, utilizing a continuous infusion schedule. PMID- 1428729 TI - Phase I clinical trial and pharmacokinetic evaluation of doxorubicin carried by polyisohexylcyanoacrylate nanoparticles. AB - Doxorubicin (DXR) incorporated into biodegradable acrylate nanoparticles such as polyisohexylcyanoacrylate (PIHCA) has been shown to increase DXR cytotoxicity and reduce cardiotoxicity by modifying tissue distribution in preclinical studies. We have conducted a phase I clinical trial of DXR-PIHCA in 21 patients with refractory solid tumors (10 male, 11 female, median age: 53 years, median PS: 1, prior free-DXR therapy: 7 patients). A total of 32 courses at 28 day intervals were administered at 6 dose levels (15, 30, 45, 60, 75 and 90 mg/m2). The drug was given as a 10 minute IV infusion on day 1 to the first 5 patients: 2 of them presented a grade 2 allergic reaction (W.H.O. criteria) during infusion, which was rapidly reversible once drug administration was discontinued. Subsequently, in the other 16 patients, the administration was modified to a 60 minute i.v. perfusion diluted in 250 cc of Dextrose 5%: only 1 patient presented the same allergic reaction. Grade 2 fever and vomiting occurred in 9 patients and 7 patients respectively during the first 24 h after treatment. There was no cardiac toxicity among the 18 evaluable patients. Grade 3 or 4 hematologic toxicity occurred at the 75 and 90 mg/m2 dose level. The dose limiting toxicity was neutropenia. The maximum tolerated dose was 90 mg/m2 and the recommended phase II dose was 75 mg/m2. A pharmacokinetic evaluation of DXR-PIHCA was conducted in 3 patients each at a different dose level (60, 60 and 75 mg/m2) and was compared with free DXR given to the same patients in the same conditions. PMID- 1428730 TI - Phase II study of didemnin B in advanced colorectal cancer. AB - Didemnin B is a depsipeptide derived from a Caribbean tunicate (sea squirt) that has demonstrated antineoplastic activity against a variety of murine tumor models, including the L1210 and P388 leukemia, the B16 melanoma, and M5076 sarcoma cell lines. Based on these data, we designed a phase II trial in which 15 patients with measurable, unresectable colorectal cancer were treated with Didemnin B at an initial dosage of 3.47 mg/m2 over 30 minutes administered by intravenous infusion every 28 days; the dosage was altered in accordance with the toxicity observed, with only one patient requiring a dosage reduction for pronounced nausea and vomiting. No hematologic or nonhematologic toxicity developed. No complete or partial responses were observed. These results do not compare favorably with results of treatments using other single agents or combinations that are currently available for the treatment of advanced colorectal cancers. However, because of the tolerable levels of toxicity experienced by in our patients, it is possible that an insufficient dose of the medication was delivered. We concluded that Didemnin B is not active against of colorectal cancers at the dosage and schedule at which it was administered in this study. PMID- 1428731 TI - A phase II study of interleukin-2 and interferon-alpha in head and neck cancer. AB - The capacity to modulate host response against metastatic head and neck cancer may eventually lead to improved survival. This phase II study in patients with advanced head and neck cancer evaluated the efficacy of combination systemic recombinant interleukin-2 (IL-2) and interferon-alpha (INF-a) and evaluated laboratory correlates between tumor response and a) tumor differentiation and b) NK cell activation. Five of fourteen patients responded; two had partial responses and three had transient responses (one complete and two partial, each lasting less than four weeks). Patients that responded had relatively lesser tumor burden and poorly-differentiated metastases. No response was observed in those few individuals in whom natural immune function was only minimally enhanced by therapy. Major toxicity, including but not limited to fever, fatigue and pulmonary compromise, allowed only 3 of 14 patients to complete three cycles of therapy. This preliminary phase II study shows that combination IL-2/INF-a therapy has clinical anti-tumor activity and that the level of NK cell activation and the degree of tumor differentiation may correlate with response. PMID- 1428733 TI - A study of toxicity and comparative therapeutic efficacy of vindesine-prednisone vs. vincristine-prednisone in children with acute lymphoblastic leukemia in relapse. A Pediatric Oncology Group study. AB - Vindesine (des-acetyl Vinblastine) is a synthetic derivative of vinblastine, and was produced with the hope that it would have less neurotoxicity and hematopoietic toxicity than other vinca alkaloids. Phase I and II studies also demonstrated significant activity in lymphoid malignancies, especially Acute Lymphoblastic Leukemia (ALL). The present study was designed to compare therapeutic effectiveness of twice weekly vindesine (2 mg/M2/dose) plus Prednisone (60 mg/M2/dose) (Treatment 1) to weekly Vincristine (2 mg/M2/dose) plus Prednisone (60 mg/M2/day) (Treatment 2). All patients were less than 21 years of age, and had documented bone marrow relapse (blast count > 25%). In 39 patients presumed sensitive to vincristine, there were 11 complete responses out of 20 patients (55%) randomized to receive vindesine/prednisone and 7 complete responses out of 19 patients (37%) treated with Vincristine/Prednisone. In 37 patients resistant to vincristine, there were 7 complete responses (19%). Vindesine was more toxic than Vincristine. Major toxicities of vindesine included paraesthesias, peripheral neuropathy and ileus. Vindesine hematological toxicity appeared greater, but such toxicity is hard to assess in patients with bone marrow disease. In this study, vindesine and vincristine had similar efficacy, but vindesine use was associated with more toxicity. PMID- 1428732 TI - A phase II trial of interferon alpha-2A plus fluorouracil in advanced renal cell carcinoma. A Hoosier Oncology Group study. AB - In vitro studies have documented the synergistic activity of interferon (IFN) and fluorouracil (5-FU) in human cancer cell lines, and recent clinical trials have demonstrated the efficacy of this combination in metastatic colon cancer. The current study was undertaken to evaluate the combination of IFN alpha-2a plus 5 FU in previously untreated patients with metastatic renal cell carcinoma. From May 1990 through August 1990, 14 patients with metastatic renal cell carcinoma were treated with 5-FU 750 mg/m2/day continuous infusion IV days 1-5, followed by weekly IV infusions of 5-FU 750 mg/m2 beginning on day 12. Patients concurrently received IFN alpha-2a 9 x 10(6) IU subcutaneously 3 times per week beginning on day 1. The median age of patients treated was 57 (range 38-80) with a median Karnofsky performance status of 90 (range 60-100). Sites of metastases included lung only in 6 patients, liver only in 1 patient, 1 patient had bilateral disease at presentation, and the remaining patients had multiple sites of metastases. The median duration of therapy was 2 months. The predominant toxicities seen were stomatitis, nausea, flu-like symptoms and neurotoxicity. The only grade IV toxicity observed was severe vomiting in 1 patient, though 5 patients discontinued therapy within 2 months because of poor subjective response. With a minimum follow-up of 13 months no objective responses were seen. Thirteen of the 14 patients have had progressive disease and 11 have died. The median time to progression was 2 months (range 0.5-6 months) and the median survival was 5 months (range 2-14.5 + months).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428735 TI - Meteorologic influences on the frequency of pulmonary embolism. AB - RATIONALE AND OBJECTIVES: Reports published earlier this century suggested that meteorologic factors influence the incidence of pulmonary embolism. These observations were based on few patients and often lacked rigorous standards of evidence. In the current study, the authors evaluate the association between barometric pressure changes and pulmonary embolism using radionuclide ventilation perfusion (V/Q) scan data. METHODS: Daily interpretation data for V/Q lung scans were correlated retrospectively with daily local barometric pressure changes over a 7-year period. RESULTS: The incidence of pulmonary embolic disease was significantly related to a decrease in barometric pressure during the 3 days preceding clinical presentation. CONCLUSIONS: Meteorologic factors are less important than better-known risk factors for pulmonary embolism; however, their effect is demonstrable in a large data sample. This work confirms previously published associations between barometric pressure changes and the incidence of pulmonary embolism. PMID- 1428734 TI - Post-ligation dilatation of the fallopian tube. AB - RATIONALE AND OBJECTIVES: Dilatation of fallopian tube remnants after ligation has been described but never systematically studied in post-ligation hysterosalpingograms (HSGs). This study describes the frequency and appearance of proximal tubal remnant dilatation as seen on HSGs in women with a history of bilateral tubal ligation (BTL). METHODS: A retrospective review of medical records and a subjective and objective evaluation of dilatation seen on HSGs included 68 consecutive women seen for pre-reanastomosis HSG. RESULTS: Among the 68 women, 44 (67%) had objectively measured dilatation on one or both tubes. Dilatation was present in both short and long tubal remnants. There were no measurable differences between women with and without presence of dilatation. Neither length nor dilatation of tubal remnant was associated with pregnancy outcome. CONCLUSIONS: Dilatation of the tubal remnant after bilateral tubal ligation is a common finding on HSG and can be accurately identified from the HSG by radiologists. Dilatation is not strictly related to length, and in our small sample with follow-up, was not associated with pregnancy outcome. PMID- 1428736 TI - Image feature analysis of false-positive diagnoses produced by automated detection of lung nodules. AB - RATIONALE AND OBJECTIVES: To reduce the number of false-negative diagnoses by radiologists, the authors are developing a computer-aided diagnosis scheme for detection of lung nodules in digital chest images. In this study, the authors attempted to reduce the number of false-positive diagnoses obtained with a previous computer scheme by incorporating additional knowledge from experienced chest radiologists into the computer scheme. METHODS: The authors applied their previous computer scheme, using less-strict criteria, to 60 clinical chest radiographs; this yielded 735 candidate nodules (23 true nodules and 712 false positive diagnoses). These candidates were analyzed using region-growing, trend correction, and edge-gradient techniques to determine measures by which to quantify image features of candidate nodules. RESULTS: The 712 false-positive diagnoses represented various anatomic structures that were located throughout the chest image. From this analysis, we were able to decrease the number of false positive errors from an average of 12 to approximately 5 per image without eliminating any true nodules. CONCLUSION: Our results show that incorporating knowledge from experienced chest radiologists into the computer algorithm will play an important role in the development of computerized schemes for the detection of pulmonary nodules. PMID- 1428737 TI - Visual increment and decrement threshold curves as a function of luminance range and noise in simulated computed tomographic scans. AB - OBJECTIVES: The effect of luminance range compression on the visual threshold of a target in a computed tomographic (CT) scan was investigated in eight experiments. METHODS: Both visual increment thresholds of a hot target and visual decrement thresholds of a cold target were obtained. Realistic noisy CT images simulating a scan reconstruction and partial volume blurring were tested as representative of complex medical images. Negative versions, high luminance versions, and noise-free versions of these CT images also were tested. RESULTS AND CONCLUSIONS: In all the noisy images, as the luminance range of the image was compressed, proportionately smaller physical luminance differences between the target and its local background were needed to reach visual threshold. However, the thresholds were the same in terms of the difference in CT numbers between target and background. Noise in terms of CT numbers sets the threshold for a wide range of display conditions. In the noise-free CTs, as the luminance range was compressed, the luminance differences between the target and background needed to reach threshold also decreased, but only marginally. However, in terms of CT numbers, the thresholds were increased. PMID- 1428738 TI - Effects of vasoconstrictors on isolated rabbit coronary arteries exposed to isotonic iohexol. Potassium chloride-, histamine-, endothelin-, and prostaglandin F2 alpha-induced contractions on arteries exposed to iohexol without and with osmotic additions (sodium chloride or glucose). AB - RATIONALE AND OBJECTIVES: A major effect of contrast media (CM) on coronary vessels is vasodilatation, but occasionally, both ionic and nonionic media may cause coronary artery spasm. The influence of CM on the actions of vasoactive substances is not well known. To investigate the effects on rabbit coronary arteries of an iso-osmolar nonionic CM, iohexol (140 mg I/mL) the vasoconstrictors potassium chloride (KCl), histamine, endothelin, and prostaglandin-F2 alpha (PGF2 alpha) were used. The effects of iohexol with 30 to 150 mM sodium chloride (NaCl) or with 25-50 g/L glucose also were investigated. METHODS: Coronary artery segments were mounted between two L-shaped prongs in tissue baths with buffer solution. Before each investigation, buffer was exchanged with iohexol solution. Increasing concentrations of a vasoconstrictor were added, and the constriction of the vessels was recorded. RESULTS: Iohexol caused a comparatively small inhibition of the contractile effects of histamine and endothelin. This meant little reduction in maximal contraction (Emax), and the concentration of constrictory substance resulting in half maximal contraction (EC50) compared with buffer solution. Iohexol also caused a small reduction in Emax of KCl, but EC50 was significantly lower. Adding NaCl or glucose to iohexol decreased Emax and increased EC50. Iohexol inhibited most of the contractile effect of PGF2 alpha, but adding NaCl increased Emax slightly. CONCLUSIONS: The effects caused by a nonionic CM on coronary arteries cannot be attributed to osmolality alone. The CM influenced the effects of vasoconstrictors to differing degrees, but the inhibition of the CM per se was usually small. PMID- 1428739 TI - Gadolinium-ethoxybenzyl-DTPA, a new liver-specific magnetic resonance contrast agent. Kinetic and enhancement patterns in normal and cholestatic rats. AB - OBJECTIVES: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a new hepatobiliary magnetic resonance imaging (MRI) contrast agent with a dual elimination: 70% via the liver and bile and 30% via the kidney in normal rats. The abdominal enhancement patterns of this new compound and the uptake mechanism by the liver were studied in rats using tissue relaxometry and MRI. METHODS: Twelve normal rats, 33 rats treated with agents designed to inhibit biliary excretion of the agent, and 6 rats with surgically ligated common bile ducts received Gd-EOB-DTPA intravenously. Distribution and excretion were measured by MR relaxometry. MR signal intensity was measured over time for liver, kidney, and bowel. RESULTS: In normal animals, 0.1 mmol/kg Gd-EOB-DTPA induced a significantly greater (200%) and more prolonged liver signal enhancement (100% at 30 minutes) than Gd-DTPA at the same dose. Either hyperbilirubinemia, induced by common bile duct ligation, or bromosulfophtalein (BSP) infusion inhibited liver uptake of Gd-EOB-DTPA, resulting in a preferential elimination via the kidney. Taurocholate (TC), an inhibitor of the bile acid transporter, was unable to block the liver uptake of Gd-EOB-DTPA. Blood half-lives of Gd-EOB-DTPA in rats were 2.4 minutes for the first component and 8.2 minutes for the second. CONCLUSIONS: Data indicate that transport of Gd-EOB-DTPA through the liver into bile is driven by the organic anion transporter. The relation between enhancement of liver and kidney may be diagnostically useful to indirectly evaluate liver excretory function. Yet, persistent enhancement of liver, even in the presence of severe hyperbilirubinemia, should be sufficient to identify focal mass lesions. PMID- 1428740 TI - Fluorinated blood substitute retention in the rat measured by fluorine-19 magnetic resonance imaging. AB - RATIONALE AND OBJECTIVES: Emulsions of perfluorocarbons (PFCs) have been tested as blood substitutes. However, evidence exists that there is long-term retention of some PFCs by the organs of the reticuloendothelial system (RES). The authors investigate organ retention of the blood substitute component, perfluorotripropylamine (FTPA), using fluorine-19 (19F) magnetic resonance imaging (MRI). METHODS: Various dosages of an emulsion of FTPA were administered to five rats. At intervals up to 86 weeks after infusion, 19F MRI was used to measure the amount of FTPA in liver and spleen. The data were fit to both linear and exponential elimination models, and organ retention half-lives were calculated. RESULTS: The exponential half-lives for combined liver and spleen FTPA ranged from 110 to 190 days. Linear half-lives ranged from 175 to 300 days. CONCLUSIONS: FTPA retained by the liver and spleen may be quantified by 19F MRI: The half-lives that were measured are longer than those reported previously for FTPA. PMID- 1428741 TI - Changes in serum magnesium during excretory urography. A comparison of ionic and nonionic contrast media. AB - RATIONALE AND OBJECTIVES: It is known that ionic contrast media (CM) bind magnesium and that patients with asthma often benefit from magnesium injections. Similarly, asthmatics have a higher incidence of CM reactions. This work tests the hypothesis that ionic CM alter serum magnesium more than nonionic CM. METHODS: Ten patients were divided into two groups; one group received iothalamate and the other received iohexol. RESULTS AND CONCLUSIONS: The total magnesium level changed significantly from baseline in the iothalamate-treated group (P less than .01). Iothalamate produced a significant decrease in protein bound magnesium (P less than .01) with a significant increase in filterable magnesium (P less than .01). Iohexol did not produce significant changes for any of the magnesium fractions. The patient with the most clinically significant adverse reaction (though minor) had the lowest baseline magnesium level. Further studies with larger groups including patients with asthma are needed. PMID- 1428742 TI - Spinal instrumentation. Evolution and state of the art. PMID- 1428743 TI - Emergency radiology services at medical schools in the United States. AB - RATIONALE AND OBJECTIVES: Little has been published on the delivery of emergency radiologic services in academic radiology training programs. METHODS: The author surveyed 127 medical schools in the United States concerning aspects of radiology services for their emergency rooms, including who interprets images, what training in emergency radiology is provided, and problems with film retrieval. RESULTS AND CONCLUSIONS: Emergency department radiographs most often are initially interpreted by a radiology resident and subsequently reviewed by a faculty radiologist who does not have a major interest in or time commitment to emergency radiology. Most schools describe problems such as disappearance of emergency department films and a paucity of provided clinical information. Only one third of schools provide formal instruction in emergency radiology for their radiology residents. PMID- 1428744 TI - Computer-aided radiopharmaceutical design. AB - The ultimate goal of a QSAR analysis is prediction, which depends on the elaboration of the most appropriate set of molecular descriptors. As such, molecular description is the nucleus of QSAR and in the absence of exhaustive molecular description, rational drug design may be greatly impeded. As previously discussed, computational methods such as quantum mechanics and molecular mechanics provide molecular description at a fundamental level which then enhances the descriptive capability and predictive power of a QSAR analysis. In recognition of these capabilities, semi-empirical molecular orbital methods and molecular mechanics now have been incorporated into or interphased with QSAR programs. Such integrated packages are being successfully used in computer-aided molecular modeling. Computer-aided molecular modeling can provide the three dimensional structure of a molecule, its chemical and physical characteristics, comparisons of structures of different molecules, and visualization of complexes formed between them. From the foregoing, predictions may be made about how related new molecules may function. Thus, the combination of quantum and/or molecular mechanics and QSAR provides a formidable weapon in the chemist's armamentarium. The molecular modeling approaches are certainly more practical to use than physicochemical methods. They also provide electronic and thermodynamic data that are not available from x-ray crystallographic data. Of course, these techniques are not confined to radiopharmaceutical development and they also could aid in the development of contrast agents for radiography or magnetic resonance imaging. We believe that as computational resources and capabilities increase over the next decade, computer-aided drug design will become a standard procedure in all drug development laboratories. PMID- 1428745 TI - Hypertrophic pyloric stenosis: volumetric measurement of nasogastric aspirate to determine the imaging modality. PMID- 1428746 TI - In a heartbeat. Interview by David Reiser. PMID- 1428748 TI - Gun control response. PMID- 1428747 TI - Leading is better than following. PMID- 1428749 TI - Opiate addiction in Iowa. AB - Where do opiate addicts obtain drugs? Interviews with patients in an Iowa methadone clinic reveal some surprising responses with definite implications for physicians who prescribe. PMID- 1428750 TI - Hippocrates at graduation. PMID- 1428751 TI - Physician involvement in accounts receivable. PMID- 1428752 TI - Expression of cauliflower mosaic virus ORF II in a baculovirus system. AB - The cauliflower mosaic virus ORF II encoding the aphid transmission factor (ATF) was mutagenized to introduce a BamHI restriction site upstream from the initiation codon and then cloned into an eukaryotic viral expression vector (Autographa californica nuclear polyhedrosis virus). All recombinant viruses tested in Spodoptera frugiperda (SF21) cells expressed a protein of about 18 kD which comigrated in PAGE with ATF from infected plants. Western blotting using an oligopeptide antiserum to ATF confirmed the identity of the 18-kD protein from infected cells as the product of the ORF II sequences (P18). Subcellular fractionation of cells infected with the recombinant AcMNPV demonstrated that the expressed P18 accumulated intracellularly in an insoluble form. Antiserum was produced in rabbit against the partially purified P18 expressed in SF21 cells. When used to immunogold label ultrathin sections of cauliflower mosaic virus (CaMV)-infected turnip tissue, this antiserum was shown to be highly specific, labelling only the electronlucent inclusion bodies (containing P18) and not other plant cellular components. PMID- 1428753 TI - Differentiation of biologically distinct cucumber mosaic virus isolates by PAGE of double-stranded RNA. AB - Electrophoresis on 5% polyacrylamide was used to analyze dsRNAs of 26 cucumber mosaic virus isolates propagated in Nicotiana tabacum. There was variation between isolates in the migration of each of the dsRNAs 1, 2, and 3. Comparison of the dsRNA profiles enabled each isolate to be allocated to 1 of 7 distinct dsRNA profile types. Two distinct and readily distinguishable isolates were mixed in planta and dsRNA from these infected plants compared with in vitro mixtures of them. All bands from both types were present, indicating that the differences were real and reproducible. This method is of value as a means of classifying cucumber mosaic virus isolates, as it more closely reflects a range of biological characteristics than do other methods currently used. PMID- 1428754 TI - Common identity of grapevine viroids from USA and Australia revealed by PCR analysis. AB - Pairs of viroid-specific oligonucleotide primers were selected and used in separate reverse transcription reactions coupled with the polymerase chain reaction to obtain DNA products of predetermined sizes characteristic of each viroid. The reaction conditions allowed efficient incorporation of small amounts of 32P-dATP which enabled rapid detection of the products in polyacrylamide gels. Using this method as well as probe hybridization, the presence of grapevine yellow speckle viroids 1 and 2 (previously known as GV1B) in grapevine samples from California was demonstrated, and it was established that the Australian grapevine viroid occurs in California. These comparisons provide the basis for uniform nomenclature of grapevine viroids found in different geographical regions. PMID- 1428755 TI - Cloning and mapping of EcoRI, HindIII, and PstI fragments of bovine herpesvirus 4 (DN-599) genome. AB - EcoRI, HindIII, and PstI restriction fragments representing the entire genome of the DN-599 isolate, the American prototype strain, of bovine herpesvirus 4 (BHV 4) were cloned. These cloned restriction fragments were analyzed by restriction enzyme digestion, hybridization to Southern blots of BHV-4 (DN-599) DNA, and cross-hybridization of cloned fragments. The resulting data were used to construct restriction maps of the unique region of BHV-4 (DN-599) DNA for restriction enzymes EcoRI, HindIII, and PstI. The EcoRI and HindIII restriction maps confirm those previously deduced for the DN-599 isolate by hybridization of cloned fragments of a European strain of BHV-4 to Southern blots of DN-599 DNA. The PstI restriction map is the first reported for BHV-4. PMID- 1428756 TI - Emergency appendicectomy: a one year audit. AB - A retrospective study of emergency appendicectomy over a one-year period at Beaumont Hospital was carried out. The overall normal appendicectomy rate was 22.8%, and was twice as high in women (31%) as in men (15%). Gangrenous or perforated appendicitis was present in 20% of cases. The overall mean assessment surgery interval was 16.7 hours. Considerable variation in the use of antimicrobial agents was noted in the study, and many haematological and radiological investigations performed did not appear to improve diagnostic accuracy. Among patients with clinical features typical of appendicitis, 16% proved to have a normal appendix. These results point to a number of aspects of the diagnosis and management of appendicitis where there appears to be room for future improvement. PMID- 1428757 TI - Public health nursing in Ireland: the general practitioners' view. AB - Present health policy in Ireland is directed towards a shift in emphasis from the provision of services on a hospital inpatient basis to a community or outpatient basis. This study set out to elicit views of general practitioners (GPs) in relation to the home visiting activities of the nursing services in the community. Of the thirty-five (76%) GPs whose questionnaires were included in the analysis, 88% were satisfied with the quality of nursing services provided by the public health nurse (PHN) but were dissatisfied with access to service (37%), out of hours service (48%) and communication with PHNs (25%). Eight GPs had contact with public health nurses on a weekly basis, 11 had contact monthly and 14 had contact three monthly or less frequently. For chronic conditions requiring dressings, over 70% of GPs refer to the PHN and when given a choice, 25% of GPs would refer these conditions to a registered general nurse (RGN). Care by an RGN or nurses' aide for conditions such as monitoring of vital signs, continence care and administration of enemas, was found acceptable by 50% of GPs. The findings indicate that there is need for review of the structure of the nursing services in the community. PMID- 1428758 TI - The self-perceived health needs of the rural elderly who live alone. AB - A randomised cross-sectional survey of Public Health Nurses (PHN) registers was carried out in two rural counties, Westmeath and Longford, Ireland. 200 elderly people living alone, consisting of 50 aged 65-74 years in each of the two counties and 50 aged > or = 75 years expressed their health needs in terms of physical, mental and social well-being. 50% lived in accommodation with inadequate bathroom facilities and only 38.9% were content with their current accommodation. 37.9% felt their finances were inadequate while 15.7% were unsure of their eligibility for different entitlements. 17.6% had personal experience of crime. 39.4% lacked a means of obtaining emergency help. The majority (61.7%) perceived themselves as enjoying excellent/good health. The unmet demand for services, other than transport, varied from 11.6% for laundry services to 0% for PHN visits. Transport services were judged inadequate by 51.5% of the study group. It is concluded that by analysing and cross-analysing in terms of variables used in this study, aspects of health care needs could be targetted for different subgroups within the elderly alone group. While not complete in themselves they would help in the targetting of scarce resources. PMID- 1428759 TI - Argyrophylic nucleolar organiser regions (AgNOR's) as a prognostic indicator in breast carcinoma. AB - Silver staining nucleolar organiser regions (AgNOR's) were determined in archival histological specimens of breast carcinoma. Representative samples from forty eight female patients were counted manually for AgNOR's--median 3.85 (range 1.1 10.2 AgNOR's per cell). Taking the median value of 3.85 as a cutoff, the patients were divided into two groups: A = Those with AgNOR counts > 3.85; B = Patients with AgNOR counts < or = 3.85. The 5 year survival was 21% in group A and 85% in group B (p < 0.001). There was no significant correlation between AgNOR's and tumour size, lymph node status, tumour grade, menopausal status and oestrogen receptors. We conclude that nucleolar organiser regions may be useful as a prognostic indicator in breast carcinoma especially in patients in whom other prognostic information is unavailable. PMID- 1428760 TI - Skin cancer in an Irish renal transplant population. AB - One hundred and forty-nine renal transplant patients attending 2 centres in Dublin were examined. Twelve patients (8.1%) were found to have cutaneous malignancy while dysplastic lesions (premalignant and/or malignant) were identified in 34 (22.8%). The prevalence of cutaneous malignancy in this study is substantially greater than that of previous Irish studies. The introduction of cyclosporin A (CyA) as a new and more effective immunosuppressive agent in renal transplantation may in part explain this increase. PMID- 1428761 TI - Abdominal pain in pre-menopausal women. PMID- 1428762 TI - The skin in pregnancy--recent advances. PMID- 1428763 TI - Robert Kane's Gold Medal Essay of 1829. PMID- 1428765 TI - Perinatal mortality 1988. AB - This is the 10th Annual Report of Perinatal Mortality in the Republic of Ireland, based on figures supplied to the Institute of Obstetricians and Gynaecologists by the Obstetrical staff of the Units listed on page 453. Details were available for 53,346 of the 54,815 babies born in 1988. Data is included about all infants dead or alive who at birth weighed 500 grams or more. PMID- 1428766 TI - Perinatal mortality 1989. AB - This report complements the 1988 figures reported earlier in this edition of the Journal. Data were available for 50931 of the 51659 babies born in 1989 weighing 500 grams or more. These were supplied by the Units listed in Table I. PMID- 1428764 TI - Treatment of medullary carcinoma of the thyroid by laryngo-pharyngo oesophagectomy--a case report. AB - We report the case of a 34 year old man, who presented with advanced medullary carcinoma of the thyroid gland. His initial presentation, with dysphagia, is unusual in this condition. Surgery is the treatment of choice, radiotherapy and chemotherapy being relatively ineffective. Our patient underwent pharyngo-laryngo oesophagectomy which is rarely performed in these cases, as such extensive disease is not often amenable to surgery. PMID- 1428767 TI - The potential for casemix in Ireland. PMID- 1428768 TI - Progression from partial to generalised lipodystrophy--a case report. AB - Lipodystrophies are rare disorders of adipose tissue metabolism. Two forms are recognised--partial or generalised. Though loss of body fat is a common feature these have been considered mutually exclusive clinical entities making any unifying pathophysiological concept difficult. We report, for the first time, a case of partial lipodystrophy affecting the face which progressed to become generalised. PMID- 1428769 TI - Teenage girls attending a Dublin sexually transmitted disease clinic: a socio sexual and diagnostic profile. AB - Over a 12 month period, 32 teenage girls attended the sexually transmitted disease clinic in the Mater Misericordiae Hospital, Dublin for the first time, accounting for 17.8% of all first visits. Their mean age was 18.2 years (range 15 19 years). Twenty-four (75%) were from social class V. Five (15.6%) were abusing drugs. The mean age of first coitus was 16.1 years (range 13-19 years). The mean number of sexual partners was 1.8 (range 1-5). Four (12.5%) had been sexually abused in the past. Fourteen (43.8%) had never used contraception. Twenty-three (71.9%) were nulligravidae: 2 were diagnosed as being pregnant in the clinic. Twelve (37.5%) were unaware of cervical cytology screening. Of 29 having intercourse without condoms, none considered themselves to be at risk of contracting HIV from their present partner. A total of 26 diagnoses were made in 23 patients (71.9%). The most common diagnosis was ano-genital condylomata acuminata (6, 18.8%); Chlamydia trachomatis was located in 2 patients and Neisseria gonorrhoea in one. Mild to moderate dyskaryosis was reported in 4 cervical smears (12.5%). This data highlights the need for priority targeting of this high risk group. PMID- 1428770 TI - The lymphatic circulation. PMID- 1428771 TI - Paediatric renal transplantation in Ireland: 1980-1990. AB - Between 1980 and 1990, 862 renal transplants were performed at our unit. Forty six of these were given to 38 children. The mean age of the children was 8.6 years. Reflux nephropathy accounted for 39% of the primary renal diseases, followed by congenital disorders (30%), and glomerulonephritis (16%). Seventy percent of the grafts were from cadaveric donors. The one year patient survival was 90%, and the one year graft survival 61%. Seven children received a second graft with a one year graft survival of 71%. PMID- 1428772 TI - "Avoidable mortality" as an index of health care outcome: results from the European Community Atlas of "Avoidable Death". AB - The history of the European Community Atlas of "Avoidable Death" is given. Data from the second Atlas are presented. For all causes of death except asthma there was a decrease in mortality in the period 1980-1984 with respect to 1974-1978. Taking the EC as a whole as the standard (100) population the standardised mortality ratio (SMR) in Ireland in the period 1980-1984 for tuberculosis was 160, for asthma 180 and maternal mortality 58. Ireland had the highest mortality for tuberculosis in both time periods. Asthma mortality increased in all countries except Scotland between 1974-1978 and 1980-1984. Ireland had one of the highest declines in maternal mortality over the two time periods. Within Ireland tuberculosis mortality was highest in the Mid-Western Health Board and lowest in the North-Western Health Board. Asthma mortality was highest in the Western Health Board and lowest in the Mid-Western Health Board. Maternal mortality was highest in the Midland Health board and lowest in the Southern Health Board. PMID- 1428773 TI - Indomethacin and ethamsylate alone and in combination for the relief of post episiotomy pain. AB - In a bid to minimise dosage and possible side-effects when relieving post episiotomy pain, the NSAID Indomethacin was studied in combination with a systemic haemostat Ethamsylate which has been shown to selectively inhibit some prostaglandins. Comparative groups also took Indomethacin alone and placebo in a double blind non-crossover comparison. Efficacy was judged in terms of side effects and assessments of pain intensity, pain relief and global assessment of pain. There was some evidence of a beneficial interaction between Indomethacin and Ethamsylate when adjustments were made for the patient's age and initial pain score. Side-effects were most common in the combination therapy group. PMID- 1428774 TI - Clinical audit in intensive care--the Meath Intensive Care Audit. AB - Audit is now recognised as being an essential component of clinical practice. We report on the first year of the Meath Intensive Care Audit (MICA). This audit was instituted to investigate the activity of the unit, to assess the feasibility of continuous audit in our ICU and to provide data for future development of ICU facilities. Two hundred and fifty four patients were admitted between July 1st 1990 and June 30th 1991. The mean age at admission was 58 years and the mean length of stay 5.2 days. The mean APACHE II score was 16. Thirty four patients (13.4%) died in the ICU and 17 patients died in hospital following discharge from the unit bringing the hospital mortality rate to 20%. The audit proved feasible to implement and data collection is now accepted as a routine part of our ICU work. PMID- 1428775 TI - The epidemiology of tuberculosis in a geographically defined area. Eastern Health Board Tuberculosis Advisory Committee. AB - This paper profiles the epidemiology of tuberculosis in a geographically defined area, the Eastern Health Board. In 1990, 191 new cases of the disease were notified, 15.5/100,000. One hundred and eighty five were from the indigenous population. Fifty four per cent were male. Nearly 50% of all cases occurring in females do so in those under 35 years and for males, 45% occur in those less than 45 years. One hundred and three (54%) had pulmonary tuberculosis alone and only 50 (26%) had a presumptive diagnosis. Although the lower social classes were overrepresented, cases occurred throughout all social classes and a significant proportion were either gainfully employed or in full time education. Data on BCG status was incomplete, however 28 cases were known to have had BCG at some stage of their life. Thirteen cases were also known to be HIV positive. The contact tracing process was responsible for locating 33 (17%) cases. Continuing surveillance both at national and local level is required in order to assist eradication. PMID- 1428776 TI - Dr. Donal Burke Memorial Lecture. The place of academic general practice in a medical school. PMID- 1428777 TI - Psychiatry, moral management and the origins of social policy for mentally ill people in Ireland. PMID- 1428779 TI - The relationship between a nutritional index and acute physiology score in critical illness. AB - Prognostic indices derived from available physiological data (SAPS), complex nutritional and biochemical tests (PNI), grip strength and serum albumin were calculated in 16 critically ill patients receiving intravenous nutrition over a six week period. The aim was to compare these independently derived prognostic indices, to assess their response to feeding, and to determine suitability for use in Irish intensive care units. Mean SAPS (7.6 +/- 0.92), PNI (3.1 +/- 0.29), serum albumin (30.3 +/- 1.03 g/l) and grip strength (17.9 +/- 1.3%) were all suggestive of an "at risk" group. Significant associations were found between the accepted SAPS index and both PNI (r = 0.6, p < 0.001, n = 35) and grip strength (r = -0.68, p < 0.001, n = 44) but not with serum albumin. No consistent improvement was seen in response to feeding in any of the derived indices. The close correlation between prognostic indices derived from either physiological, nutritional or grip strength data in this study and the failure of prognostic indices to improve during hyperalimentation would support a common mechanism, e.g. endogenous mediators, for metabolic and physiological disturbance in critical illness. It suggests that the role of hyperalimentation is supportive rather than therapeutic and re-iterates the importance of managing underlying disease processes. Simple grip strength may be a useful alternative to complex nutritional indices. PMID- 1428778 TI - The role of free radicals as mediators of endothelial cell injury in hyperhomocysteinemia. AB - Hyperhomocysteinemia has been suggested as a potent new risk factor for premature cardiovascular disease. Homocsyteine can induce endothelial cell injury but the mechanism is not understood. The purpose of this study was to evaluate the role of free radicals as potential causes of endothelial cell injury in a case-control study of obligate heterozygotes for cystathionine beta-synthase deficiency. Firstly, free radical production as measured by neutrophil chemiluminescence in obligate heterozygotes for cystathionine beta-synthase deficiency was compared with age- and sex-matched normal subjects. Secondly, the response of the cellular antioxidant system was examined by measuring the enzymes superoxide dismutase and glutathione peroxidase, their cofactors (selenium, copper), vitamin E and vitamin A in heterozygotes and normal subjects. Analyses of neutrophil chemiluminescence, vitamin A and E, glutathione peroxidase, selenium and copper showed no difference between heterozygotes and controls. While superoxide dismutase activity was higher in heterozygotes than normal subjects, the difference did not reach statistical significance and the hypothesis of excess free radical production as a mechanism of injury was not confirmed. However, further examination of superoxide dismutase activity in a larger number of subjects would be of interest. PMID- 1428780 TI - Human erythrocyte contains a factor that stimulates the peptidase activities of multicatalytic proteinase complex. AB - A novel biological factor that stimulates the peptidase activities of multicatalytic proteinase complex (MPC) has been identified and partially purified from human erythrocytes. The stimulatory factor enhances trypsin-like, chymotrypsin-like and peptidyl-glutamyl peptide hydrolyzing activity of MPC in a dose related manner. At saturating concentration of the stimulatory factor, MPC increases the activity to a different extent (10 to 56 fold) depending on the substrate used to assay the enzyme. The stimulatory factor does not hydrolyze neither amino-blocked peptides which are used to assay MPC nor typical substrates for amino and diamino-peptidases. The stimulatory factor is characterized by a high molecular mass (300 kDa) and an extreme instability since it loses the activity at 46 degrees C in 10 min and at 4 degrees C within a week. The stimulatory activity is inactivated by incubation in acidic or alkaline media, and by treatment with protease V8, but it is relatively resistant to the action of trypsin. It has been suggested that the novel stimulatory factor herein described is a protein or a protein complex which may modulate the function and the activity of MPC by association-dissociation interaction. PMID- 1428781 TI - Linoleic acid metabolism in brain cortex of aged rats. AB - The linoleic acid metabolism was examined in the brain cortex of 4 month-old and 24 month-old rats. After the injection of [1-14C]-linoleate into the lateral ventricle of the brain the animals were sacrificed at 1,3 and 6 hours from the injection. The linoleate (18:2) incorporation into lipids, the presence of fatty acid peroxidation products, as well as the 18:2 transformation into elongated and desaturated derivatives were determined. Both an age-related reduction in linoleate incorporation rate into glycerophospholipids and a decrease in fatty acid turnover were found. Furthermore, in glycerophospholipids from 24 month-old rat brain cortex a higher level of hydroperoxide derivative of linoleate was found as compared to 4 month-old animals, and this damaged fatty acid is eliminated more slowly in aged rats than in adults. Finally, unlike 4 month-old animals, a stimulation of the transformation rate of linoleate into desaturation (6,9,12-C18:3) and elongation (8,11,14,C20:3) products was found in 24 month-old rat brain cortex. On the contrary, as far as arachidonic acid (one of the most important end products of the mechanism of linoleate modification) is concerned, the differences between aged and control animals were small, making it quite difficult to attribute a physiological meaning to this phenomenon. PMID- 1428782 TI - The neuropsychological consequences of HIV infection in drug addicts. AB - The occurrence of neuropsychological impairment in asymptomatic, HIV-positive individuals is controversial. In the present study we compared the performance of three groups of chronic intravenous drug abusers (HIV negative, asymptomatic HIV positive, AIDS) on a battery of neuropsychological tests. While the AIDS group was significantly impaired, no difference was found between HIV negative and HIV positive asymptomatic subjects on any measure. This finding is in agreement with the results of studies of homosexual and bisexual subjects, indicating that the presence of HIV infection in the asymptomatic stage does not carry an added risk of cognitive impairment in drug addicts. PMID- 1428783 TI - Prevention of ischemic stroke: the role of carotid endarterectomy in symptomatic patients. AB - Carotid endarterectomy (CE) has recently been proved to be beneficial in symptomatic patients with severe (70-99%) appropriate carotid stenosis. After discussing the historical evolution of CE as a possible preventive treatment of ischemic stroke, we review the results of North American and European trials in order to give practical information for the management of cerebrovascular patients. PMID- 1428784 TI - Comparison of two medications in central nervous system toxoplasmosis in patients with AIDS. AB - We retrospectively examined 39 patients with AIDS and central nervous system toxoplasmosis in order to determine the efficacy and safety of two combinations: pyrimethamine-sulfadiazine and pyrimethamine-clindamycin. The results showed a response rate of 79% for the sulfadiazine association and a high failure rate in the clindamycin group. Side effects with sulfadiazine were slightly more frequent, but with desensitization protocols discontinuation was kept down. The combination of pyrimethamine and sulfadiazine, associated, when necessary, with desensitization schedules, was confirmed to be first choice therapy for cerebral toxoplasmosis in AIDS patients. The role of alternative regimens needs further evaluation. PMID- 1428785 TI - Acute axonal idiopathic polyneuropathy: a Guillain-Barre syndrome variant? AB - We report 7 cases of acute polyneuropathy fitting the NINDS diagnostic criteria for GBS. Electrophysiological study and sural nerve biopsy revealed a picture of axonal polyneuropathy, without changes suggesting demyelination. We discuss whether the acute idiopathic axonal neuropathy belongs to the GBS spectrum or represents a separate clinico-pathological entity. PMID- 1428786 TI - The cerebrospinal fluid in the diagnosis of tuberculous meningoencephalitis: review of the literature. AB - We review the literature on the biochemical, cytological and immunological changes in the cerebrospinal fluid (CSF) in tuberculous meningoencephalitis, emphasizing the inconsistency and low specificity of the CSF findings described in classic accounts of this disease. We consider separately the possible causes of yellow or bloody fluid. The development of accurate techniques of analysis does not diminish the importance of the clinical findings and history in the early diagnosis of this disease. PMID- 1428787 TI - Gliomatosis cerebri. Report of a case with isolated amnesic disorders. AB - We describe the case of a female patient with behavioral and memory disorders. A neuropsychological evaluation confirmed the absence of mental deterioration and the presence of the psychometric features of the amnesic syndrome. The clinical diagnosis was supported by MRI and histological examination. PMID- 1428788 TI - Clinical and neuroradiological findings in a case of pure word deafness. AB - Pure Word Deafness is a clinical syndrome included among the aphasias and is marked by complete deafness of sudden onset with conserved ability to understand and read the written word and with no speech disorders. We report the case of 61 year old man in whom pure word deafness developed after two episodes of acute cerebral ischemia in quick succession. Neuroimaging procedures, that is: computed tomography scan, single photon emission computed tomography and magnetic resonance imaging, revealed the presence of two ischemic lesions in the temporal cortex bilaterally. Neurophysiological investigations (electroencephalogram, brainstem auditory evoked potentials and stapedial reflex) were also studied. We discuss the outcome of all these investigations in the light of the relevant published work. PMID- 1428789 TI - MRI demonstration of the cerebellar damage in diffuse hypoxic-ischemic encephalopathy. Case report. AB - MRI demonstrated symmetric putaminal and cerebellar changes in a patient who survived a cardiorespiratory arrest due to acute idiopathic polyneuritis. Since similar aspects can be observed following cyanide or methanol poisoning differential diagnosis from these conditions has to rely on the combination of clinical and imaging findings. PMID- 1428790 TI - Paroxysmal dystonia due to a lesion of the cervical cord: case report. AB - A 48 year old woman complained of mild weakness and paresthesias of the left limbs, followed 15 days later by episodes of paroxysmal dystonia of the left limbs occurring several times daily over 10 day period. Magnetic resonance imaging (MRI) of head and neck revealed a small area of altered signal in the T2 weighted sequences in the left posterolateral quadrant of the cord at the second cervical vertebra. An MRI scan 18 months later showed no lesion. This is the second case of paroxysmal dystonia with a single MRI lesion in the cervical region on record. PMID- 1428791 TI - Wallenberg syndrome and trigeminal herpes simplex. PMID- 1428792 TI - Neoadjuvant chemotherapy in the treatment of recurrent glioblastomas (GBM). AB - We wondered whether second line chemotherapy in recurrent GBM patients might be useful for debulking the tumor mass and improving patient performance status to prepare the way for second surgical intervention. We have treated 18 recurrent glioma patients with high dose methotrexate (HDMTX) plus 5-fluorouracil (5FU). 5 Patients were responders, 6 had stable disease, and 7 disease progression. 5 patients, 3 PRs and 2 SDs, underwent a second operation after two chemotherapy cycles. Disease progression resumed at 11.5 +/- 7 weeks in the non reoperated patients, and at 32.6 +/- 9.3 weeks in the reoperated group from initiation of neoadjuvant treatment. Survival time in reoperated patients was 82.6 weeks. Although our experience with this policy is still limited, we believe that reoperation in selected recurrent GBM patients can be worthwhile. PMID- 1428793 TI - Autonomic nervous system function in myotonic dystrophy. AB - Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group. PMID- 1428794 TI - Transient topographical amnesia. AB - A woman experienced three isolated episodes of loss of topographical memory, without overt etiology. A rare form of selective non verbal transient amnesia, similar to the more common transient global amnesia, is postulated. PMID- 1428795 TI - The primary antiphospholipid syndrome: case report. AB - Lupus anticoagulant antibodies and anticardiolipin antibodies are acquired circulating immunoglobulins that interact with phospholipids. These factors may exert anticoagulant properties in vitro and so interfere with coagulation tests that use phospholipids. These antibodies are not, however, associated with a hemorrhagic diathesis. Indeed, despite their name and their in vitro anticoagulant properties, they have been associated right from the earliest reports with systemic and cerebral thromboembolic episodes. We report the clinical and instrumental findings in a patient with ischemic stroke and anticoagulant antibodies in the serum. PMID- 1428796 TI - Cerebral ischemia and livedo reticularis in a patient with impairment of coagulation factor VII and free protein S. AB - The association of ischemic cerebrovascular lesions with livedo reticularis is known as Sneddon syndrome. It affects young subjects, primarily women, and its neurological manifestations are TIAs, ischemic stroke, progressive dementia and epileptic seizures. Its etiopathogenesis has still to be clarified. Some authors have associated it with an antiphospholipid antibody syndrome. Recently it has been assumed that a defect in blood coagulation may be involved in its pathogenesis. Here we report a case in which both an increase in coagulation factor VII activity and a deficiency in free protein S were documented. PMID- 1428797 TI - Chronic spastic atrophic hemiparesis with benign course. AB - We present the clinical and neuroimaging data of 4 patients (mean age: 62 years, range 54-67; mean follow-up: 19.5 years, range: 26 months-29 years) with chronic spastic atrophic hemiparesis (CSAH). Neuroimaging findings were non specific, CT scan and MRI showing white matter lesions located within the centrum semiovale in two cases, parieto-occipital lobe and pons in one case each. This study underlines that patients with CSAH may have a good long-term prognosis. MRI studies may demonstrate associated lesions within the white matter or brainstem and are advisable in all subjects with CSAH, but further studies are necessary to clarify the nature of the observed lesions. PMID- 1428798 TI - Metachromatic leukodystrophy: on an atypical case. AB - We describe an atypical case of juvenile metachromatic leukodystrophy. Motor conduction velocity was still within the normal range 3 years after clinical onset, in contrast to what is commonly found in this disease. Another unusual feature is the normal level of CSF protein. These data are discussed in the light of the sural nerve biopsy findings, which revealed only slight impairment. PMID- 1428799 TI - Veralipride-induced tardive dystonia in a patient with bipolar psychosis. AB - Veralipride is a benzamide derivative effective in the treatment of menopausal syndrome. Despite its antidopaminergic action, extrapyramidal side effects seem to be very uncommon. We observed a patient with bipolar psychosis, who developed segmental dystonia after taking the drug. The disorder slowly receded in 14 months, but reappeared during neuroleptic therapy a few months later. To the best of our knowledge, this is the first case of veralipride-induced tardive dystonia, and the affective disorder might have predisposed our patient to the development of this tardive side effect. PMID- 1428800 TI - Occupational health in Israel: research and prevention approaches for the 1990s. PMID- 1428801 TI - Review of a decade of activity in occupational safety and health in Israel. PMID- 1428802 TI - Occupational health planning in Israel: a U.S. perspective. AB - In order to indicate priorities for possible occupational health care planning activities, we evaluated occupational health risks, health services, and occupational research and training in Israel from the perspective of occupational medicine in the United States. We used available public information as well as data collected in a previous regional assessment of occupational health in the Negev. We estimated that each year 35% of the workforce in Israel may be exposed to high levels of noise, 4-11% to workplace toxins, and 7% to work injuries, all hazards warranting attention by health planners. Reviewing occupational health services we found that programmatic deficiencies limit the effective use of existing resources. We also evaluated the potential benefits of strengthened expert review in setting funding priorities for research and training in occupational safety and health in Israel. PMID- 1428803 TI - Occupational and environmental exposures and nonspecific lung disease--a review of selected studies. AB - Selected studies show that nonspecific lung diseases are a major occupational and environmental health hazard. Exposure to mineral dusts (such as cement and brown coal) and organic dusts (cotton, hemp and flour) as well as manganese and gaseous irritants causes significant upper respiratory tract injury. Possible additive effects of mixed exposures, combined exposure to dusts and gaseous irritants of the upper respiratory tract, individual susceptibility, and mechanisms of nonspecific respiratory effects of exposures are considered. Interpretation of the results is difficult due to uncontrolled confounding. Measures for preventing lung impairments include exposure reduction and preemployment examination of workers. PMID- 1428804 TI - Primary prevention of occupational lung disease: a view from the United States. AB - Occupational lung diseases are an important source of preventable morbidity and mortality in the United States. A significant proportion of lung cancer, mesothelioma, asbestosis and the other pneumoconioses, asthma, and chronic obstructive pulmonary disease, is caused by well-established occupational agents, especially among selected subgroups of the general population. Primary prevention of this set of diseases requires identification and control of workplace hazards. In the United States, data from inspections undertaken by the Occupational Safety and Health Agency, and from periodic surveys conducted by the National Institute for Occupational Safety and Health, show that respiratory toxins are commonly found in the workplace. Workplace-based education, surveillance and exposure reduction and elimination are essential components of a strategy to prevent occupational lung disorders. PMID- 1428805 TI - Occupational cancer in Israel: an overview. AB - Occupational cancer is a result of exposure to carcinogens in the workplace. The critical interaction during the initiation stage of the carcinogenesis process occurs between the ultimate form of a carcinogen and the DNA, resulting in the formation of a DNA adduct or several types of gross structural alterations. Several methods have been developed by which carcinogens can be detected. These methods can be utilized for ambient monitoring of exposure and health surveillance. "Molecular epidemiology" is the combination of epidemiologic and laboratory studies, i.e., monitoring exposure by measuring the DNA adduct. Early detection of occupational cancer is difficult, due largely to the latent period which can be up to 20 years or more. For this reason it is important to develop and improve techniques for early detection of premalignant changes. Israel has numerous workers who are exposed to carcinogens, but has no special legislation concerning the use of carcinogenic substances in the workplace. However, an interministerial committee has published, and is continuing to work on, exposure and safety regulations. Medical surveillance and prevention as well as legislation are necessary to reduce morbidity and mortality from occupational cancer. PMID- 1428806 TI - Sentinel markers for industrial disasters. AB - Workers, managers, and occupational health and safety inspectors can be trained to detect or recognize and promote action to correct sentinel markers for industrial disasters. A sentinel marker is defined as a pre-disaster warning sign of impending failure in prevention. Administrative sentinel markers are: a weak occupational health and safety program; lack of spontaneous access to top management; failure to accept responsibility for subcontractors; the absence of written disaster plans and drills for emergency response in the factory and the adjacent community; noninvestigation of prodromal leaks, exposures, spills or injuries; punishment of "troublesome" individuals reporting such prodromal events; nonuse or misuse of data on illness, injury and absenteeism; and suboptimal work conditions and supervision of shift workers. Information sentinel markers include absence of worker and community right-to-know programs, nonuse of data on earlier mishaps from similar technologies, and failure to provide toxicologic data to hospitals in the pre-disaster phase. Technological sentinel markers are: absence of fail-safe controls, interlocks and automated alarm systems driven by real-time monitoring. Transportation sentinel markers include suboptimal vehicle standards, and drink, drugs and fatigue in drivers. Preventive programs based on identification of all sentinel markers by workers are suggested to be more effective than selective action based on risk assessment analysis. PMID- 1428807 TI - Regional differences in cancer incidence and mortality in Israel: possible leads to occupational causes. AB - Occupational causes of cancer are difficult to establish because of the long latency period and difficulty in identifying occupational linkages. This study provides a regional analysis of cancer incidence and mortality as a method of identifying localizing factors in cancer that can be followed by more specific epidemiologic investigation. In this study we analyze the regional standardized mortality ratios (SMRs) for site-specific cancers, by age, sex and continent of birth for the years 1983-86, for the Jewish population of Israel. Elevated total malignant and benign neoplasm SMRs were found in Acre (SMR 109, P < 0.05), Haifa (104, P < 0.05) and Tel Aviv (107, P < 0.001). The only other statistically significantly elevated SMRs were found in Acre for lung cancer (133, P < 0.05) and leukemia (171, P < 0.05). Age and sex-standardized incidence ratios (SIRs) by regions are also presented for the years 1980-81 for the Jewish population. Haifa had elevated SIRs for colorectal cancer (126, P < 0.001), breast cancer (118, P < 0.01) and lymphomas (126, P < 0.05). Elevated lung cancer SIRs were found in both Acre (145, P < 0.05) and Ramla (143, P < 0.05). Male to female incidence ratios (MFIRs) for ages 30+ for the Israeli Jewish population are also presented. Elevated bladder cancer MFIRs were found in the heavily industrialized Haifa region (7.69 vs. 4.62 P < 0.05). For Ramla residents, bladder and oronasopharyngeal cancer MFIRs were approximately three times the national average (not statistically significant). Ramla also had elevated MFIRs for lung cancer (14.9 vs. 3.4 nationally, P < 0.01), as did Acre (7.6 vs. 3.4 nationally, P = 0.06). These elevated MFIRs are suggestive of occupational exposure from the cement and asbestos factories in the Ramla and Acre regions. Regional analyses of cancer mortality and cancer incidence (using SMRs, SIRs and MFIRs) can serve as a basic tool for identifying sentinel markers of excess rates. Our findings indicate regions where we should undertake case-referent studies in order to identify potential risk factors and where to target possible preventive programs. PMID- 1428808 TI - Mesothelioma mortality among former asbestos-cement workers in Israel, 1953-90. AB - Asbestos workers have long been recognized as a high risk group for the development of mesothelioma and other cancers. In this study we collated from a variety of sources 26 mesothelioma deaths that occurred between 1978 and 1990 among a cohort of some 4,441 former workers from an asbestos-cement plant in northern Israel. Since the expected number of deaths for this number of Israeli males in this age-group over this period is 0.12 cases, the risk of this disease was more than 223 times the national rate, age and sex adjusted [standardized mortality ratio (SMR) = 22,351, P < 0.001]. The mean years of exposure of persons who died from mesothelioma was 16.2 (SE 2.5). The mean latency period for mesothelioma cases from onset of exposure to death was 25.6 years (SE 1.3). Additional follow-up systems are needed to ensure complete reporting of asbestos related diseases, including epidemiologic follow-up of asbestos-exposed workers after cessation of their work, with regular analysis of death and cancer registry data for high risk groups. Asbestos-related cancer is an important element in cancer epidemiology that requires further development in Israel. Studies of former workers, their families and of persons who worked or attended school adjacent to the asbestos-cement factory, as well as follow-up of other former worker groups exposed to asbestos are recommended. PMID- 1428809 TI - A follow-up study in a lead smelter community following the introduction of an effective pollution control system. AB - A follow-up study using biological and environmental monitoring was performed in a lead smelter community to assess the health risk of inhabitants and to establish how long it takes after the introduction of an effective emission control system to declare a lead-contaminated area safe for normal living. In specific population groups (mothers and children) biological indicators of lead exposure and lead effect on hemoglobin synthesis were determined 2 years before and 11 consecutive years after the installation of bag filters. At the same time lead was monitored in the airborne and deposited particulates, in household dust and in soil. The results clearly show that the process of normalization is rather slow. The difference in blood lead and erythrocyte delta-aminolevulinic acid dehydratase between the exposed and control groups, even 12 years after bag filters installation, was still remarkable. It appears that soil, contaminated with lead from past exposure, is a major source of increased lead absorption in a population for many years. PMID- 1428810 TI - Responses of occupational physicians and laboratory staff to reports of high blood lead levels. AB - We evaluated the responses of physicians specializing in occupational health and of laboratory personnel engaged in occupational lead monitoring when periodic blood lead analysis results exceeded the Biological Exposure Index (BEI). Legally, Israeli workers must be removed from the site of occupational lead exposure after a repeat test shows "value above BEI" (VABEI). The maximum legal period between a report of VABEI and the repeat test is 14 days. Physicians have the discretion to remove workers after the first VABEI test if deemed necessary. In 1987-88, 242 of 3,776 analyses had a VABEI, 167 of which were periodic tests. The average laboratory response time between receipt of the sample and VABEI reports to occupational physicians was 13 days (SE = 0.4). Medical records of 100 workers who had 134 tests with a VABEI were available. In 35 (26.1%) of these events the physicians recommended removing the workers from the exposure source, in 55 (41.0%) events the physicians required repeat tests, and in 44 (32.9%) they neither recommended removal nor repeated the tests. The minimum time lapse between the first and repeat test was 20 days. The second test yielded 24 VABEI. Physicians recommended removing workers from the source only in 13 (54.2%) of these cases. This study suggests that the system must be improved in order to ensure the proper response to VABEI results. PMID- 1428812 TI - Lead poisoning: II. Biological standards for occupational lead exposure--where do we stand now? AB - Lead poisoning is an occupational and environmental disease of great public health concern. During the past two decades major efforts have been made in many countries to minimize exposure to lead both in the occupational and general environment. Blood lead concentrations at which adverse effects can be detected have become progressively lower. Despite legislation concerning medical surveillance of lead-exposed workers and improvement in environmental control measures that took place during the 1980s, review of recent surveillance data indicates that excessive lead absorption among workers is still a problem in Israel. An approach is suggested for the reporting of surveillance data that will provide safety managers with the information necessary for introducing effective environmental control measures. PMID- 1428811 TI - Lead poisoning: I. Some clinical and toxicological observations on the effects of occupational lead exposure among firearms instructors. AB - Lead poisoning continues to be a common occupational disease in many countries. During the past two decades, poisoning presenting with overt clinical symptoms has become less frequent because of improvement in control of exposure, and attention has been focused on subtle biochemical and "subclinical" manifestations of lead toxicity. Firearms instructors constitute an occupational group at risk for excessive exposure to lead from the firing of arms in shooting galleries. This paper summarizes clinical and toxicological observations among lead-exposed firearms instructors and illustrates the wide spectrum of clinical and laboratory abnormalities that may occur in this occupational group. As clinical research has advanced, significant biochemical and clinical aberrations have been detected at progressively lower blood lead levels both among occupationally exposed adults and among children who are exposed to lead in the general environment. The latter is of great public health concern and has spurred efforts worldwide to reduce human exposure to lead to an absolute minimum. PMID- 1428813 TI - Medical findings in nickel-cadmium battery workers. AB - Thirty-eight workers from a factory producing nickel-cadmium and other types of batteries came to us for medical evaluation. They included 21 women and 17 men (seniority 2-20 years, age range 31-63 years), and represented a self-selected subset of 700-900 ever-employed and 200+ recently or currently employed workers in the factory. Thirty-four worked on the nickel-cadmium assembly line. Symptoms and signs included: headache in 34; weakness, fatigue and lassitude in 26; dizziness in 16; pruritus and skin eruptions in 37; gingivitis, teeth loss and caries in 34; nasal congestion, nosebleeds and anosmia in 30; cough, phlegm production, wheezing and shortness of breath in 26; "asthma" in 14; bone pain in 18; urinary frequency, beta 2 microglobulinuria and kidney stones in 17; and sterility or multiple abortions (33) in 8 of 21 women. One additional patient had died from an "amyotrophic lateral sclerosis-like syndrome", while CT scans in six workers revealed brain atrophy. One other worker had leukemia, and two had died from cancer (lung and pancreas). Those who had worked for more than 10 years had more symptoms and signs than shorter-term employees, especially neurological illness, bone pain and urinary tract problems, including beta 2 microglobulinuria. Past blood and urinary cadmium levels were in the range of 1.6 8.7 micrograms/dl and 8-306 micrograms/l, respectively. Our findings indicated that: a) health risks for workers were not confined to the nickel-cadmium assembly line or to older workers, b) hazardous exposures still existed and illness appeared in new workers after a clean-up and intervention program, and c) exposures involved increased risks for renal disease and cancers. Finally, there is a need to control exposures and determine health risks in the full cohort of those ever employed, in the workers' children, and in the surrounding environment (air, ground, water) due to the dumping of waste from the plant. PMID- 1428814 TI - Residual neurobehavioral impairment in a water technician exposed to hydrazine containing mixtures. AB - Residual neurobehavioral impairment in concentration, comprehension, memory, task performance and mood status persisted in a water technician with respiratory and dermal exposures to hydrazine-containing mixtures prior to treatment with steroids for concurrent thrombocytopenia. The findings call attention to the possibility that residual neurobehavioral impairment may be an effect of exposure to hydrazine mixtures. PMID- 1428815 TI - Cytogenetic changes in ethylene oxide-exposed workers: a challenge to occupational medicine. AB - Ethylene oxide is a colorless gas that can cause neoplastic disease (leukemia, stomach cancer) in animals and humans. Its mutagenic potential is expressed by chromosome aberrations and sister chromatid exchange, as has been shown in numerous studies of groups exposed to ethylene oxide. The results of our pilot study on the effects of exposure to high levels of ethylene oxide show chromosome breakage in exposed individuals at twice the frequency of the normal population. Although these are preliminary findings, they justify urgent, specific protection from further exposure. PMID- 1428816 TI - Early detection of changes in kidney function in workers exposed to solvents and heavy metals. AB - Increases in urine concentration of specific proteins have been proposed as early indicators of deleterious changes in kidney function. Four urinary proteins (albumin, superoxide dismutase, transferrin and N-acetyl-beta-D-glucosaminidase) were measured in workers exposed to heavy metals and solvents. None of the workers had clinical evidence of renal disease or hypertension. Workers exposed to mercury had a significant increase in urinary transferring, superoxide dismutase levels were slightly increased in workers exposed to solvents and lead, follow-up of these workers is needed to confirm that these changes predict late clinical deterioration of kidney functions. PMID- 1428817 TI - Predicting increases in skin temperature using heat stress indices and relative humidity in helicopter pilots. AB - We used measurements of heat stress in the cockpit of Bell 206 and 212 helicopters manned by a crew of two to predict changes in the skin temperatures of 50 pilots over a 1-h ground standby period. Cockpit wet bulb globe temperatures increased from 28.1 +/- 5.6 degrees C to 32.9 +/- 3.9 degrees C over the 1-h ground standby period. Skin temperatures increased from 34.7 +/- 1.1 to 35.4 +/- 1.1 degrees C, while heart rate increased from 79.4 +/- 9.6 to 82.6 +/- 9.8 bpm. Cockpit wet bulb temperatures explained 26.9% of the variance of the increase in skin temperature (P = 0.0002). Wet bulb globe temperatures, discomfort index and dry bulb temperatures did not improve the predictive value of wet bulb temperatures alone. Relative humidity was not significantly associated with the increase in skin temperature. We conclude that wet bulb temperatures predict changes in skin temperature as well as other heat stress indices. Furthermore, despite high cockpit temperatures, pilots experienced only minimal strain during the 1-h ground standby period. Extrapolation of our results to the effects on body temperature of higher degrees of heat stress and physical activity is unwarranted and deserves further study. PMID- 1428818 TI - Motion sickness-like syndrome among tank simulator drivers. AB - A military tank driving simulator has recently been introduced as a training aid for tank drivers in the Israel Defense Forces. Reports of nausea and vomiting among the first users of the simulator launched our investigation of the possible existence of a motion sickness-like syndrome among simulator drivers. Although the 59 subjects drove the simulator without any report of vomiting, other motion sickness-like symptoms were frequently reported. A comparison of symptoms reported after simulator and real tank driving show that dizziness, nausea, disorientation and hypersalivation were more frequently reported by simulator drivers and were of greater intensity. However, sweating and drowsiness were more prevalent among real tank drivers. The objective effect of driving the simulator was evaluated by instability and performance tests that were conducted before, during and after driving the simulator. A greater decrement in test results was observed among subjects reporting higher frequency of motion sickness-like symptoms. PMID- 1428819 TI - Prevalence of low back pain in employees of a pharmaceutical company. AB - The association of low back pain (LBP) with mechanical factors at the workplace is uncertain. Most of the studies on this subject did not examine multiple levels of symptoms and did not take into account both the type of work and the primary activity during work. We studied the annual prevalence, severity and duration of attacks of LBP recorded on a physician-administered questionnaire in 208 workers in a pharmaceutical factory. Symptoms were then cross-tabulated with job type, location, work requirements, gender, and years at the factory. LBP was reported by 138 (66.3%) of the workers. Although over 75% of jobs in the packing department, laboratories and offices required prolonged sitting, LBP was most prevalent among workers in the packing department, where the chairs were found to be ergonomically unfit (odds ratio 3.7, 95% confidence interval 1.5-9.1, P = 0.003). Logistic regression demonstrated a highly significant and independent association between LBP and work in the packing or production department (odds ratio 2.03), sitting or lifting (odds ratio 1.97) and 6 years seniority (odds ratio 1.64). Gender was not a significant variable. We conclude that among these pharmaceutical company employees, prolonged sitting and work in the packing or production departments were independently associated with LBP. Prospective studies are warranted to substantiate our findings. PMID- 1428820 TI - Contrast sensitivity and the near point of accommodation after work with a visual display unit. AB - After several hours of work with a visual display unit (VDU), operators become myopic for a short time. Such transient myopia may be evaluated by measuring contrast sensitivity to a modulated grating pattern. The aim of the present study was to determine whether there are any accumulative myopic effects after 1 day of VDU work. We examined grating contrast sensitivity in a group of 13 full-time workers and in 13 office employees who used VDUs only sporadically. The results, which were compared with the near point of accommodation, clearly illustrated that there is no decrease in contrast sensitivity. In the VDU group the decrease in the near point of accommodation was uniformly distributed between zero and 1.0 diopter, whereas among the non-VDU workers 77% of the decrease was between zero and 0.25 diopter. We conclude that the myopic changes in the refractive status of operators after VDU work are not evident in a decrease in contrast sensitivity. However, in VDU workers the dynamic range of accommodation was smaller, suggesting that the visual fatigue and visual stress that developed at work hindered visual activities after work. PMID- 1428821 TI - Training in oculomotor tracking: occupational health aspects. AB - Smooth pursuit and optokinetic nystagmus were repeatedly examined in nine patients who sustained hemilateral brain injury. The follow-up period extended over several months of the in-hospital rehabilitation phase. Five of the patients were trained for 3-10 weeks to improve tracking responses using a biofeedback technique; the remaining four patients were not trained and served as a control group. In all patients in the first group gain responses improved and the recovery time constant increased at a rate higher than that in the untrained group. We suggest that our training procedure can be extended to other types of patients with impaired smooth pursuit tracking and may also benefit workers in need of good tracking performance. PMID- 1428822 TI - Noise exposure, noise annoyance and their relation to psychological distress, accident and sickness absence among blue-collar workers--the Cordis Study. AB - This study examined the impact of chronic industrial noise exposure on psychological distress symptoms, accident involvement and sickness absence among male and female workers. It also examined whether workers expressing high noise annoyance were more adversely affected by it. Subjects were blue-collar workers, 1,680 males and 688 females, who participated in the Cordis Study. Noise exposure levels were: low [< 75 dB(A)], moderate [75-84 dB(A)], and high [> or = 85 dB(A)]. For males, noise exposure level affected job dissatisfaction and post work irritability, while for females it also intensified somatic complaints, anxiety and depression. All the distress symptoms were higher for females. Further analysis showed that the significant increase of symptoms with noise exposure level was only for workers reporting high annoyance. Higher noise exposure levels were associated with increased accidents and sickness absence for both sexes. Noise-annoyed males had a significantly higher percentage of accidents when exposed to moderate noise levels and a marked increase in sick leave at high noise levels. Finally, the nonauditory effects studied here were already prevalent at moderate noise exposure levels, especially among noise annoyed workers. This indicates the importance of reducing even moderately high levels of industrial noise not usually considered harmful to hearing. PMID- 1428823 TI - Sleep-wake cycle in shift workers on a "clockwise" and "counter-clockwise" rotation system. AB - The present study investigated the effects of a 5-day rotating work schedule in the advance, or "counter-clockwise", vs. delay, or "clockwise" direction, on subjective and objective measures of sleep-wake cycles. Twenty-two workers (mean age 27.5 +/- 4.6 years) were studied in the counter-clockwise direction, and 11 workers (mean age 29.83 +/- 5.93) were studied in the clockwise direction. Each worker was studied for a complete rotation cycle (20 days). Sleep-wake cycles were measured by wrist-worn actigraphs in 1-min bins. The clockwise direction was associated with significantly earlier sleep times during the night shift, and with a better synchronization of workers' sleep-wake cycles during night and evening shifts. The present results provide support to the claim that rotating shiftworkers can better adapt to clockwise than counter-clockwise rotations. PMID- 1428824 TI - Absence from work among smokers and nonsmokers in Israeli industries--the Cordis Study. AB - While the negative economic effects of cigarette smoking are frequently examined in terms of the costs of health services and potential years of life lost, data on the indirect costs due to absence from work in Israel are scarce. During 1985 87, cigarette smoking habits and absence due to illness and accidents were examined in 5,826 employees (4,177 men and 1,649 women) in Israeli industry, screened in the framework of the Cordis Study. The absenteeism data related to the period 1986-87. Among men, smokers were absent an average of 2.6 days per employee more than nonsmokers (P < 0.001) over the 2-year period after adjusting for age and occupational category. Among women there was no significant difference in sickness absenteeism between smokers and nonsmokers. The excess days lost among male smokers was only partly explained by increased absence due to respiratory illness. Accident rates did not differ by smoking habits. There is a significant increase in absence due to illness among men employed in Israeli industry, which may be attributed to cigarette smoking. Since cigarette smoking continues to be a common practice, the overall costs to the economy may be considerable. PMID- 1428825 TI - Sickness absence in 21 industrial plants in Israel (1986-87)--the Cordis Study. AB - A population of 6,016 men and women working in 21 factories in Israel was screened for cardiovascular risk factors in the course of the Cordis Study. Sickness absence was analyzed to obtain overall indices and distributions by disease groups. Factors such as sex, age, and type of occupation were introduced. Most indices were higher for women than for men, for older workers than for younger, and for blue-collar than for white-collar jobs. Loss of scheduled workdays was estimated at 5%; at this rate, loss of revenue for the manufacturing industries (excepting diamonds) may amount to as much as half a billion dollars. PMID- 1428826 TI - A pilot occupational health service for small enterprises: first year experience- the Givat Shaul project. AB - An experimental Occupational Health and Safety Center was established as a pilot project for Israel in the Givat Shaul industrial area of Jerusalem. The center provides occupational health services to those working in its vicinity and is particularly oriented to employees of small enterprises (i.e., fewer than 20 employees). In addition to the routine occupational health services supplied by each occupational health clinic in Israel, the Center's staff also performs safety and hygiene inspections at workplaces, and provides social care services for the working population of the area. This paper summarizes the first year of the project's activities, particularly those of the clinical staff and the safety technician. Projected future activities are also outlined. The effectiveness of this project is currently under study and will be finally evaluated by an independent Hebrew University research team. If their evaluation shows the project to have been successful, establishment of similar centers in other parts of the country will be considered. PMID- 1428827 TI - Findings in pre-employment examinations. AB - Results of comprehensive pre-employment examinations of about 8,600 persons were analyzed. The most frequent findings are those related to the more prevalent risk factors and morbidity (of adults) in industrialized countries. Of special interest were the associations found between low level of education (or socioeconomic status), exposure to various occupational hazards, and poor life style habits. These findings attest to the need for providing preventive follow up (intervention) services to complement any large-scale screening program. Such services could be developed, relatively simply, based on existing occupational medicine units. The advantages and pitfalls of utilizing multiphasic screening technology in general and in occupational health settings are discussed. PMID- 1428828 TI - Realizing the potential of social work in occupational health. AB - Potential problems in occupational health that are suitable for social work intervention are illustrated by data obtained in a study of textile industry workers. Significant differences were observed between groups of workers (newly hired, veteran, and currently unemployed) on self-rated health, frequency of health problems that interfere in role function, smoking, and frequency of alcohol consumption. In addition, health behaviors varied by sex, age, educational achievement and ethnic origin among newly hired workers. These results indicate the need to identify target groups of workers when designing and implementing health prevention/health promotion programs. A model of social work practice in occupational health is presented based on different types of health behavior (preventive health behavior, illness behavior, sick role behavior and rehabilitation) and intervention modes in social work practice (individual treatment, group work, family therapy and policy and program planning). PMID- 1428829 TI - Exposure of workers to toxic substances and physical hazards: the law in theory and practice. AB - Israel has an enviable legal framework to protect the worker from exposure to dangerous substances at the workplace: a duty of the employer to inform the worker of exposure to dangerous substances; a duty of the employer and the occupational doctor to report exposure, disease and death to the factory inspectorate; and a comprehensive network of occupational doctors in place to find early symptoms of exposure in order to prevent disease. Unfortunately this framework has not been effective enough. In some instances--the Isabest factory in Naharia and the Tadiran factory in Ekron--the system has failed miserably. PMID- 1428830 TI - [Nature is dead, long live nature!]. PMID- 1428831 TI - Casey and the resuscitation of Roe v. Wade. PMID- 1428832 TI - The summer of our discontent. PMID- 1428834 TI - A pregnant fellow. PMID- 1428833 TI - A pregnant fellow. PMID- 1428835 TI - Parenthood and frozen embryos. More than property and privacy. PMID- 1428836 TI - Body, self, and the property paradigm. PMID- 1428838 TI - From a craft to an industry. PMID- 1428837 TI - Do the right thing: Minnesota's HealthRight Program. PMID- 1428839 TI - Transplantation through a glass darkly. PMID- 1428840 TI - Leaving the field. PMID- 1428841 TI - Genetics and the moral mission of health insurance. AB - Deciding whether genetic differences among individuals are morally relevant to health insurance requires us to ask, What kind of good is health care? and, What principles should govern its distribution? There are good reasons to doubt that "actuarial fairness" is an adequate description of genuine fairness in health insurance. PMID- 1428842 TI - Oregon's disability. Principles or politics? PMID- 1428843 TI - Oregon's denial. Disabilities and quality of life. PMID- 1428844 TI - Letting her go. PMID- 1428845 TI - Twenty years after. The legacy of the Tuskegee Syphilis Study. When evil intrudes. PMID- 1428846 TI - Twenty years after. The legacy of the Tuskegee Syphilis Study. Outside the community. PMID- 1428847 TI - Twenty years after. The legacy of the Tuskegee Syphilis Study. The dangers of difference. PMID- 1428849 TI - The investment of a lifetime. PMID- 1428848 TI - The Tuskegee legacy. AIDS and the black community. PMID- 1428850 TI - A right to exit? PMID- 1428851 TI - Unilateral decisions. PMID- 1428852 TI - Vain wisdom all, and false philosophy. PMID- 1428853 TI - Insurance for the insurers. The use of genetic tests. AB - Genetic testing raises concerns that individuals will be denied health insurance (and thus, effectively, access to health care), or that employers will screen to eliminate potentially costly workers. Although we as a society do not yet concur on the degree to which private businesses have a responsibility to promote social justice, several different policy alternatives might allow us to weigh the interests of insurers, as businesses, against the interests of citizens in a responsible manner. PMID- 1428854 TI - Acral lentiginous melanoma: case studies from Kauai. AB - Cutaneous malignant is generally regarded as a skin cancer of Caucasians. However, one subtype, acral lentiginous melanoma (ALM), has an equal distribution among all ethnic groups and is the variant most common in non-Caucasians. In its early stage it is difficult to recognize and, unless diagnosed early, has a very poor prognosis. Herein, we present 3 cases of ALM seen on Kauai in 1990. PMID- 1428855 TI - Race, ethnicity and birth-weight: Hawaii 1983 to 1986. AB - A study of racial/ethnic-specific mean infant birth-weights reported on 1968 to 1972 live birth-weight certificates for Oahu, Hawaii is reviewed here. The 1983 to 1986 data confirm those earlier results: (a) The Hawaiian group is significantly heavier in mean birth-weights than other cohorts during the preterm period (33 to 36 weeks gestational age); (b) statistically significant differences also were present in mean birth-weights for the term and post-term periods (37 to 45 weeks gestational age); and (c) the ranking of cohorts from heaviest to lightest in mean birth-weights is Caucasian, Hawaiian, Japanese and Filipino respectively. The data raises 2 questions: (1) Which birth-weight standards are most applicable for Asian and Pacific Islanders; and (2) what are the implications of the race/ethnic-specific mean birth-weight differences relative to mortality, morbidity and developmental outcome? PMID- 1428856 TI - Physician-hospital networking: avoiding a shotgun wedding. AB - The erosion of the traditional market is forcing hospitals and physicians to reevaluate their historical relationships. One method for addressing the potential conflicts created by current pressures is the formation of physician hospital networks. These entities are formed and function on the basis of mutual interests and responsiveness to change. PMID- 1428857 TI - Organization of marketing in U.S. hospitals: an empirical investigation. AB - In this article the results of an empirical investigation of the marketing function in U.S. hospitals are reported. The relationship between hospital marketing orientation and hospital performance is examined. Results of the study indicate that substantial evidence exists to conclude that marketing is effective in the health care industry. Marketing failures in hospitals seem to be related to inappropriate marketing organization and inadequate top management support. PMID- 1428858 TI - Demand/capacity management in health care: an application of yield management. AB - Although the concepts of yield management have been applied successfully to many services such as hotels and airlines, the concepts have not expanded much further. Some segments of health care appear to be logical candidates to apply and benefit from the concepts, and this article addresses that application by examining the implementation of yield management in a health care facility. Not only is the implementation described, but the issues surrounding that implementation are discussed. PMID- 1428859 TI - Healthcare reform. PMID- 1428860 TI - Quality of health care and financial performance: is there a link? AB - The relation between operating margin and quality of care is investigated by using survey and financial data for 82 small and medium-sized hospitals. A positive relation between the variables is found, and implications of that relationship are discussed. PMID- 1428861 TI - Strategies for small community hospitals operating in the shadow of a medical center. AB - Small community hospitals compete with medical centers. This article presents select descriptive information and strategy considerations that are based on experiences within an 82-hospital system. PMID- 1428862 TI - Denials of staff privileges face increased antitrust scrutiny. AB - Recent court decisions and statements by federal antitrust officials indicate that hospitals may face increasing scrutiny of their staff privileges decisions. In view of these developments, hospitals must be prepared to defend their decisions from antitrust challenges and should structure their actions to satisfy the remaining defenses to antitrust claims. PMID- 1428863 TI - New directions for hospital strategic management: the market for efficient care. AB - An analysis of current trends in the health care industry points to buyers seeking high quality, yet efficient, care as an emerging market segment. To target this market segment, hospitals must be prepared to market the efficient physicians. In the coming years, hospitals that can identify and market their best practicing providers will achieve a competitive advantage. PMID- 1428864 TI - Viewpoint: managerial imperatives. AB - The development of an institutional culture cannot be left to chance. One must articulate the desirable managerial variables that will establish the mores of and for the institution. When these are known and become the basis for the actions and activities of those who are part of the institution, the operational results will be satisfactory and desirable. PMID- 1428865 TI - HCMR interview: Pat N. Groner. Interview by Montague Brown. AB - Pat N. Groner, President Emeritus, Baptist Health Care, Pensacola, Florida, is a man of ideas and action. Pat has ably led his hospital, was founder of the Hospital Research and Development Institute and Voluntary Hospitals of America, and is now a leader in higher education. Whenever and wherever Pat sees an opportunity to improve things, he jumps in with a hundred ideas, most of them real winners. He engages others and fights for constructive change. For all who seek models for the full life well lived, look at Pat Groner. PMID- 1428866 TI - [Morphology of spermatozoa and prognosis of fertility]. PMID- 1428867 TI - [Oral nickel provocation and a nickel-free diet. Indications and practical implementation]. AB - In spite of some unsolved questions, an influence of orally ingested nickel on some forms of chronic eczema is generally accepted. In cases of chronic relapsing dermatitis with typical location, positive nickel patch test and positive oral nickel challenge, a nickel-restricted diet may be recommended for a limited period of time. Regional nutritional habits should be considered in the design of diets. Indications, practice and evaluation criteria for oral nickel challenge and nickel-reduced diets are described. PMID- 1428868 TI - [The effect of neuropeptides on wound healing in vitro and in vivo]. AB - Neuropeptides constitute the largest family of extracellular messengers and have a long phylogenetic history. They and their receptors have been detected in normal human skin and related epithelial tissues. They act as neurotransmitters, hormones and paracrine factors. In skin they are involved in innervation, secretory gland function, growth control, and the regulation of blood flow. They are of remarkable interest in normal and disturbed wound healing, on three major levels: regulation of blood flow, modulation of inflammation, and trophism. Both neuropeptides and their antagonists are of potential interest as therapeutic agents. Their basic activities include immunomodulation, inhibition of inflammation, histamine release and stimulation of blood flow. PMID- 1428869 TI - [Polymorphous photodermatitis. Morphology and temporal course]. AB - From 1985 to 1990 we saw 318 patients with polymorphous light eruption (PLE). Papular (47.4%) and papular-vesicular (27.2%) skin lesions were predominant. A monomorphous picture was seen in 31%. The first lesions appeared within a median period of 19 h after sun exposure, and in 38% of cases within 5 h. In most patients (78.7%) the skin eruptions faded within 1 week of appearance (median 4 days). There seems to be a correlation between the course of light exposure and the resulting clinical morphology. Terminological and methodical problems in the classification of PLE are discussed. PMID- 1428870 TI - [Practical use of the TDF factor in radiotherapy of basalioma and squamous cell carcinoma]. AB - For X-ray therapy, the relation between single doses, number of fractions and duration of therapy have been combined in the TDF (time, dose, fraction) factor by Orton and Ellis. This factor seems to be well suited to evaluation of the X ray therapy of basal cell carcinomas and squamous cell carcinomas of the skin. A simplified TDF formula is presented, together with some methods of calculation. Furthermore, tables are presented containing TDF values for frequently applied single doses and for two to five fractions per week. In addition, some hints are given on the use of the decay factor of Orton and Ellis to compensate for the loss of X-ray effectiveness if therapy has been interrupted. PMID- 1428871 TI - [Cytologic aspects of the differential diagnosis of basalioma]. AB - Basal cell carcinoma is a common cancer of the skin with characteristic histological features. A total of 200 skin lesions suggestive of basal cell carcinoma were compared by cytology and histology correlated, 2 cases were false negative, and 4 cases false-positive. In 6 cases the material was non-diagnostic. The characteristic cytologic feature of basal cell carcinoma allowed differentiation from other tumors of the skin. If the technique and preparation are adequate, cytology is highly diagnostic for basal cell carcinomas. PMID- 1428872 TI - [Considerations of the pathogenesis of parakeratosis variegata based on morphologic and molecular genetic findings]. AB - We report on a 63-year-old woman who had been suffering from generalized parakeratosis variegata since she was 7 years old. Increased tightness of the skin was the only clinical symptom. On the whole integument except for the face, we found a fine network of hyper- and depigmentation and telangiectasias. The skin surface was dry and atrophic with fine lamellar scaling. Histological, immunohistological and ultrastructural findings indicated early infiltration by a cutaneous T-cell lymphoma. However, PCR analysis of the T-cell receptor gamma chain genes revealed multiple amplification products favouring a polyclonal T cell proliferation. In light of the clinical history over a period of 56 years, we consider parakeratosis variegata to be a benign, chronic inflammatory condition, as is confirmed by the results of PCR analysis in this patient. PMID- 1428873 TI - [Detection of the Kobner phenomenon of the skeleton of patients with psoriasis]. AB - Psoriasis is a humorally controlled systemic disease. The degree of "eruptive strength" of manifestation results from hereditary factors (disposition) and environmental factors (provocation). We were able to demonstrate that the well known Kobner phenomenon of the skin also occurs on the skeleton of patients suffering from psoriasis. We analysed 83 patients in whom bone scans were carried out. Our results indicate that provocation factors such as bacterial foci and/or trauma correlate with a significantly higher number of pathological scintigraphic findings, ranging up to "hot spots". Furthermore, not only did bone fractures remained scintigraphically positive for an unusually long time, traumas of the end phalanx could be demonstrated in 70% of psoriatic patients compared with 21% of a control group. Obviously, one factor alone or a combination of factors triggers the involvement of the skeleton as a "deep Kobner phenomenon". In psoriatic patients the response of bone metabolism to disturbance differs from that of non-psoriatic patients in that there is a long-lasting dysregulation. This explains the high correlation between skin and skeletal manifestation in psoriatics. Therefore the manifestation of psoriatic disease is due not to a single-stranded linear causal interrelation but to a multicausal "network pathogenesis". Bone scintigraphy is the diagnostic method of choice in patients with psoriatic osteoarthropathy and allows an objective evaluation of therapeutic success. PMID- 1428874 TI - [Chronic urticaria in enterobiasis vermicularis (oxyuriasis)]. AB - We report on a patient with chronic urticaria associated with enterobiasis vermicularis (oxyuriasis). The current distribution of Enterobius vermicularis and its importance concerning chronic urticaria of endogenous origin is evaluated and discussed. PMID- 1428875 TI - [Cutaneous angiosarcoma after telecobalt irradiation]. AB - Cutaneous angiosarcomas are rare neoplasms. They occur most frequently on areas of skin exposed to sunlight in the elderly, or in long-standing lymphoedema (Stewart-Treves syndrome). Radiation is an important aetiological factor. With only 1 exception, the 34 published cases of cutaneous angiosarcoma on the trunk were caused by irradiation of internal tumours, occurring between 4 and 50 years after the irradiation treatment. The prognosis quoad vitam is poor. The tumours should be removed surgically. When they are inoperable, irradiation is an alternative therapeutic option. The aim of this paper is to show the histological differential diagnosis of cutaneous angiosarcomas and to demonstrate problems with the treatment. PMID- 1428876 TI - [Painful cutis marmorata teleangiectatica congenita]. AB - A 39-year-old woman with cutis marmorata telangiectatica congenita (CMTC) on the back presented with a 5-year history of pain in the involved area which initially occurred only on touch and cold exposure but was ultimately virtually constant. Histological examination of a skin biopsy specimen revealed an increased number of nerve fibres. The phlebectatic subcutaneous veins were demonstrable by NIR (near infrared) venoscopy. PMID- 1428877 TI - [Skin and occupation: dermatologic and occupational medicine aspects. Report of the Skin and Occupation Congress: dermatologic and occupational medicine aspects of the Erlangen Dermatologic University Clinic and the Study Group of Occupational Dermatology 2 to 4 April 1992 in Erlangen]. PMID- 1428878 TI - [Therapy of lymphocytic infiltration]. PMID- 1428879 TI - [Concomitant manifestation of neurodermatitis and psoriasis]. PMID- 1428880 TI - [Graft versus host disease]. PMID- 1428881 TI - Historical perspective: a forward look, a backward look. AB - This paper summarizes how the problems of fallout, genetics, radioactive waste, and regulatory control of radiation were perceived by Dunning, Straub, Taylor, and others in 1955 at the inaugural meeting of the Health Physics Society. It was stated that health physicists had a great opportunity to resolve these problems and to avoid past mistakes. Throughout the 1950s, health physicists made major contributions to elucidating the fallout problem and contributed to its resolution, and it can be considered a success story. Waste disposal is not considered to be a success to date. A major difference has been the lack of political will to grapple with a perceived "no win" situation. The evolution of radiation limits is briefly traced over the past 37 y from voluntary standards to rigorously enforced regulations demanded by society. This paper speculates that the changing international scene makes the United States the pre-eminent nuclear power which will challenge future health physicists to maintain a balance between the control of radioactive material and its peaceful applications. PMID- 1428882 TI - Assessment of potential doses at the Maralinga and Emu test sites. AB - An assessment has been undertaken of potential doses to future aboriginal inhabitants of the Maralinga and Emu areas of South Australia, where nuclear weapons tests in the 1950s and 1960s have resulted in residual radioactive contamination. Radioactive material due to this program of tests and other experiments is still detectable several tens of kilometers from some of the test sites. Continued occupancy by individuals following an Aboriginal lifestyle could give rise to annual effective dose equivalents of several mSv within contours enclosing areas of several hundred square kilometers. The most significant dose pathways are calculated to be the inhalation of resuspended activity and ingestion of soil by infants. An analysis of the effects of uncertainties in the dose calculation has indicated the uncertainty distribution on predicted doses from the inhalation pathway. PMID- 1428883 TI - Inhalation doses for aboriginal people reoccupying former nuclear weapons testing ranges in South Australia. AB - The Australian Government plans to rehabilitate the former nuclear weapons testing ranges at Maralinga and Emu in South Australia and to allow access to the areas for the Pitjantjatjara (Aboriginal) people who are the traditional owners of the land. The major radiological hazard posed by reoccupation of the ranges arises from inhalation of residual plutonium. The committed effective dose that these people might receive from inhalation on reoccupation of the lands is computed for a range of sites. The estimated doses for permanent occupancy range up to 300 mSv y-1 indicating the need for substantial rehabilitation before these areas are suitable for unrestricted access. PMID- 1428885 TI - 14C release from a Soviet-designed pressurized water reactor nuclear power plant. AB - The Paks Nuclear Power Plant in Hungary runs with four pressurized water reactors, each of 440-MWe capacity. Sampling systems have been developed and used to determine the 14C of various chemical forms (14CO2, 14CO, 14CnHm) in the airborne releases. The average normalized yearly discharge rates for the time period 1988-1991 are equal to 0.77 TBq GWe-1 y-1 for hydrocarbons and 0.05 TBq GWe-1 y-1 for CO2. The contribution of 14CO was less than 0.5% of the total emission. The 14C discharge rate is estimated to be four times higher than the corresponding mean data of Western European pressurized water reactors. The calculated effective dose equivalent to individuals living in the vicinity of the power plant, due to 14C release, was 0.64 microSv in 1991 while the effective dose equivalent due to the natural 14C level was 15 microSv y-1. The long-term global impact of the 14C release in the operational period of the plant (1982 1991) was 1,270 man-Sv. The 14C excess in the environmental air has been measured since 1989 by taking biweekly samples at a distance of 1.7 km from the nuclear power plant. The long-term average of radiocarbon excess coming from the power plant was 2 mBq m-3. The local 14C deposition was followed by tree ring analysis, too. No 14C increase higher than the uncertainty of the measurement (four per thousand = 0.17 mBq m-3) was observed. PMID- 1428884 TI - Radiological implications of inhaled 239Pu and 241Am in dusts at the former nuclear test site in Maralinga. AB - The biokinetics of 239Pu and 241Am present in three dust samples obtained from Maralinga were investigated after their deposition in the rat lung. Results were used as an experimental basis for assessing the radiological implications for human exposure. The transfer rates of these actinides to blood in the various dusts differed by 50-fold. The most transportable forms were compatible with a material that had 25% class W and 75% class Y characteristics. The doses per unit intake for adults, children, and infants exposed to an aerosol of 5 microns AMAD were calculated to be, respectively, 0.059, 0.076, and 0.140 mSv Bq-1. The corresponding doses for the least transportable forms were the same as those calculated for a class Y compound, namely 0.036, 0.049, and 0.096 mSv Bq-1. The behavior of the actinides in humans was predicted by combining the transfer rates to blood with mechanical clearance data obtained after volunteers had inhaled 85Sr or 88Y labeled fused aluminosilicate particles. The results suggested that monitoring of 241Am in the chest could be used to advantage for assessing intakes incurred by workers involved with any further decontamination procedures but would be of little practical value for assessing inadvertent public exposure. The paper includes comments on the relevance of the 1990 ICRP recommendations and the proposed new dosimetric model for the respiratory tract. PMID- 1428886 TI - Meteorological observations at Hiroshima on days with weather similar to that of the atomic bombing. AB - An attempt to explain discrepancies between measured neutron-induced radioactivities (i.e., 152Eu, 60Co) and calculated yields based on the Dosimetry System 1986 was made by considering moist air densities at different altitudes over Hiroshima, Japan. The investigation checked the validity of moist air density estimates used in the Dosimetry System 1986 computer codes. Meteorological observations were conducted to obtain atmospheric temperature and pressure profiles for the Hiroshima area. By coupling these observations with surface measurements taken on 6 August 1945 at Ebayama Park (3.6 km from the hypocenter), estimates of temperature, pressure, and humidity at the time of detonation were derived. This allowed the calculation of densities for dry air, moist air, and water vapor. The results proved similar to the Dosimetry System 1986 estimates. Water vapor density calculations showed the largest difference (at most 7%). These results imply that the 152Eu yield contradiction in the Dosimetry System 1986 calculations vs. real measurements for large ground distances (> 900 m) is not the result of an erroneous estimate of moist air density in Hiroshima. PMID- 1428887 TI - Underground air returns as active transportation pathways for radon gas entry into homes. AB - Levels of elevated 222Rn in homes can fail to correlate with measured radium concentrations in soils and surrounding rocks for reasons which can include water sources, building materials, and unusual variations in climate or building construction. Several homes were identified in the Phoenix, AZ metropolitan area with soil radium concentrations of < 0.074 Bq g-1 (2.0 pCi g-1) which had elevated radon concentrations unexplained by geological sources alone. Continuous monitoring of eight houses under different conditions of cooling system usage revealed a definite role of the underground air returns as active transport pathways contributing to the enhancement of the indoor concentration of 222Rn in six of the houses. The ratio of indoor 222Rn concentrations on days when the cooling system was operated continuously compared to days the system was off ranged from essentially one up to a factor exceeding 10. PMID- 1428888 TI - Mitigation of elevated indoor radon gas resulting from underground air return usage. AB - Underground air returns have been found to be active transportation pathways for radon gas entry into homes. Several homes for which underground air returns were contributing to elevated indoor 222Rn concentrations were evaluated for possible mitigation. Two houses with such problems were successfully mitigated by inserting flexible ducts into the returns. In one of these houses, the initial mitigation attempt resulted in an exacerbation of the problem due to leakage of the ducting. This was solved by re-sleeving the returns using a stronger material. Mitigation of elevated indoor radon gas caused by use of underground air returns by inserting flexible ducts is not possible for all situations, especially those for which the returns are small, filled with debris, misaligned, or inaccessible. PMID- 1428889 TI - Characterization of radioactive petroleum piping scale with an evaluation of subsequent land contamination. AB - Scale formation in oilfield piping and equipment has been a problem for petroleum companies. In the past, scale waste from cleaning of piping and equipment has been considered nonhazardous. Naturally occurring radioactive material in the form of 226Ra and, to a lesser degree, 228Ra with their associated decay products have recently been discovered in the scale. Due to the lower abundance and short half-life, 228Ra is not addressed in this paper. 226Ra, an alpha emitter, is a potential internal hazard to workers from the inhalation and ingestion of the dust produced during descaling or pipe cleaning operations. Along with this, a higher-than-normal background gamma exposure rate is seen where the pipe cleaning was routinely done. An evaluation of the radiation hazards associated with a retired pipe cleaning field was performed. Gamma exposure rates, 226Ra concentration, and 226Ra leachability were examined using scale containing soil from the field. Radon emanation from the soil was also determined. PMID- 1428890 TI - The self-defining critical group and its application to a measured check of the derived limit for 125I in drinking water. AB - Using a series of daily measurements of 125I in the drinking water of North Surrey, England, from November 1988 through May 1990, the accumulated activities in the thyroids of adults drinking such water were calculated on the assumption that the fraction of ingested iodine taken up by the thyroid was f = 0.3 and the tap water consumption was C = 600 L y-1. These figures were compared with measured values of 125I activities in 42 thyroids taken at necropsy from residents in the North Surrey area who were dying during this same time period. Eight thyroids (19%) had measured activities greater than predicted, so they were named the self-defining critical group. After comparing the thyroid with the drinking water activity, the current generalized derived limit for 125I in the drinking water may be too high by a factor of 2. The reason for this appears to be the use of f = 0.3 which is the mean value for the "normal" population. Models involving critical groups should use values of parameters different from the mean. In the present case, making f = 0.6 would remove the discrepancy between measurement and prediction and would be in reasonable accord with measured distributions of f. PMID- 1428891 TI - Dosimetry study of an accidental overexposure to 192Ir gamma rays. AB - Localized irradiation of the skin and subcutaneous tissues with large single doses of gamma rays can induce delayed effects characterized by fibrosis that invades the irradiated tissues. The skin surface dose and the depth of penetration of 192Ir gamma rays, measured in phantoms and in frozen thighs of sacrificed pigs after acute single doses of irradiation and different skin-to source distances, are reported in this note. Correlations between the dosimetry and the evolution of the lesions are considered. PMID- 1428892 TI - Pleural mesothelioma in the rat following exposure to 239PuO2. AB - Pleural mesothelioma was an infrequent observation following deposition of 239PuO2 in the lung or pleural cavity. Only five tumors were found in 2,105 rats exposed to 239PuO2 aerosols in the present study, while four tumors were found in 527 rats that inhaled 239PuO2 in previously published lifespan studies. Risk of pleural mesothelioma was not significantly increased by intrapleural injection of 30 kBq 239PuO2. In contrast, a much higher incidence of peritoneal mesothelioma was seen following intraperitoneal injection of 239PuO2 due to aggregation of 239PuO2 particles on mesothelial surfaces. It was concluded that the lack of 239PuO2 aggregation on pleural surfaces is responsible for small numbers of pleural mesothelioma observed following deposition of 239PuO2. PMID- 1428893 TI - Photoneutron fields in medical accelerator rooms with primary barriers constructed of concrete and metals. AB - This study investigates the photoneutron field found in medical accelerator rooms with primary barriers constructed of metal slabs plus concrete. An increased neutron dose equivalent was observed for barriers containing lead or steel as compared to barriers fabricated entirely of concrete. The effect of the beam's size and distance from the primary barriers on the neutron dose was evaluated and the portion of the neutron dose due to the metal slabs was determined. PMID- 1428894 TI - A thermoluminescent dosimetry intercomparison in operational power station fields. AB - A dosimetry intercomparison was held among the five agencies in Canada that are recognized by the Atomic Energy Control Board as competent to perform external dosimetry. Exposures of thermoluminescent dosimeter badges were made under operational conditions to radiation fields in Candu nuclear generating stations. Details of the method are described including the large, block-type phantoms (with a rotating front face so that all badges were equally exposed) and a small device to measure the depth-dose distribution. Thirty-six exposures (or "runs") were made, exposing 522 badges for periods of 1 h-2 d. Normalization between the runs was based on the absorbed dose at 1,000 mg cm-2 for each run, as measured by the depth-dose device. Using this method, the average relative readings for the five participants ranged from 1.01-1.40 (dimensionless). PMID- 1428895 TI - Miles Technicon H.2 automated hematology analyzer. AB - Automated hematology analyzers are used in all large hospitals and most commercial laboratories, as well as in most smaller hospitals and laboratories, to perform complete blood counts (including white blood cell, red blood cell, and platelet counts; hemoglobin concentration; and RBC indices) and white blood cell differential counts. Our objectives in this study are to provide user guidance for selecting, purchasing, and using an automated hematology analyzer, as well as to present an overview of the technology used in an automated five-part differential unit. Specifications for additional automated units are available in ECRI's Clinical Laboratory Product Comparison System. We evaluated the Miles Technicon H.2 unit and rated it Acceptable. The information in this Single Product Evaluation is also useful for purchasing other models; our criteria will guide users in assessing components, and our findings and discussions on some aspects of automated hematology testing are common to many available systems. We caution readers not to base purchasing decisions on our rating of the Miles unit alone, but on a thorough understanding of the issues surrounding automated hematology analyzers, which can be gained only by reading this report in its entirety. The willingness of manufacturers to cooperate in our studies and the knowledge they gain through participating lead to the development of better products. Readers should refer to the Guidance Section, "Selecting and Purchasing an Automated Hematology Analyzer," where we discuss factors such as standardization, training, human factors, manufacturer support, patient population, and special features that the laboratory must consider before obtaining any automated unit; we also provide an in-depth review of cost issues, including life-cycle cost analyses, acquisition methods and costs of hardware and supplies, and we describe the Hemacost and Hemexmpt cost worksheets for use with our PresValu and PSV Manager CAHDModel software. Readers should also review the Clinical and Technical Overview and the articles "Miles Technicon H.2 Reports" and "Developing the Evaluation Reference Method." PMID- 1428896 TI - Final CLIA regulations. Clinical Laboratory Improvement Amendments. AB - One clinical pathologist has noted that the broad scope of CLIA means "that every testing situation in the hospital, whether in or out of the laboratory, could now be a liability for ... hospital administration." Portions of CLIA became effective September 1, 1992; thus, it is important that all appropriate personnel are aware of the requirements of CLIA and that all ancillary testing sites are accounted for. CLIA will require unprecedented coordination and cooperation between the clinical laboratory and ancillary sites. Also, clinical laboratories must comply with the sometimes more stringent state regulations and requirements of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and CAP. JCAHO, for example, has regulations specific to blood glucose monitors- regulations that demand a high level of QC, proficiency testing, and documentation. In contrast, CLIA categorizes blood glucose monitoring as a waived test. (This classification has been widely criticized by laboratory organizations, which argue that an erroneous result from a blood glucose monitor could be deadly for the patient. PMID- 1428898 TI - Loose screws in TV mounts. PMID- 1428897 TI - Marquette MAC VU 12-lead electrocardiographs. PMID- 1428899 TI - Donating and selling used medical equipment. International Medical Device Group. AB - This position paper was issued by the International Medical Device Group (IMDG) in June 1992. The group includes representatives from Finland, France, Germany, Hungary, Italy, Norway, Sweden, the United Kingdom, and the United States. ECRI is the United States representative and a founding member of IMDG. PMID- 1428900 TI - Laser technology planning. AB - Lasers continue to be a highly useful and important surgical tool, and, in today's competitive healthcare environment, they are also an effective marketing tool. The public perceives lasers to be "high-tech" instruments, associating them with excellence of care. And the availability of state-of-the-art equipment such as lasers is often critical to medical staff recruitment. However, lasers are not universal surgical tools, as some proponents suggest. They are costly, and other less expensive technologies are acceptable and sometimes more desirable for certain procedures. Also, marketing reasons alone cannot justify laser acquisition. Faced with new, more restrictive federal regulations for Medicare reimbursement of capital expenses, hospitals need effective technology planning more than ever, particularly when planning for such "high-ticket" items as lasers. They can no longer afford to acquire lasers based on the perceptions of the public or the demands of one or even a few physicians; poor planning in the past has caused many new lasers to collect dust from low utilization. (ECRI's 1991 user survey on general-purpose surgical lasers found that, on average, hospitals use lasers in less than 5% of their total surgical procedures.) Hospitals need to approach the acquisition of laser technology cautiously to ensure that the appropriate equipment is obtained, that it will be well utilized for procedures in which it offers a demonstrable improvement over alternative technologies, and that it will also conform to the overall strategic plan of the institution. The purpose of this article is to provide guidance on the technology acquisition process, whether a hospital is acquiring its first laser or has a well-established laser program.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428901 TI - Laser use and safety. AB - This Guidance Article is an update of an article published in a special issue of Health Devices entitled "Lasers in Medicine--An Introduction" (13[8], June 1984). Although surgical lasers have a good overall safety record, they do expose patients, physicians, and other clinical staff to serious risks. Laser hazards can cause injury, disability, or even death: hospital staff have been burned by misdirected laser beams, technicians and maintenance personnel have received eye injuries while working on lasers and have been exposed to hazardous chemicals while changing laser dyes, and patients have died from injuries resulting from fires ignited by laser energy. Laser accidents most commonly result from misdirection of the laser beam. Direct or reflected radiation can burn skin, hair, or, more seriously, the cornea or retina, causing permanent damage. Misdirected laser energy can also cause ignition of surgical drapes, tracheal tubes, or the patient's hair. Also, a frequent by-product of laser-tissue interactions is laser plume, or smoke. Its acrid smell and particulate matter irritate the eyes, nose, and lungs and cause nausea; it is also a suspected vector for transmitting infectious materials, such as the human papilloma virus (HPV) associated with condyloma (a wartlike lesion) and cervical cancer. The risks are not limited to patients and those directly involved in using and maintaining lasers. Many laser procedures are performed in areas outside the controlled environment of the surgical suite; patients in a waiting area or even passersby could conceivably walk into an accessible laser treatment room, such as a doctor's office, and inadvertently be exposed to a direct or reflected beam.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428902 TI - Xintec Optica 120 Nd:YAG surgical laser. AB - This update to our recent Evaluation "Surgical Lasers" (Health Devices 20[7-8], July-August 1991) provides information about the Xintec Optica 120 Nd:YAG surgical laser, which was not available at the time of our original study and which has several unique features. Xintec also offers a 50 W, 120 VAC version of this laser, the Optica 60, which we did not evaluate; the manufacturer states that these models share many of the same features. The criteria and test methods used to evaluate the Optica 120 can be found on pages 252 to 260 in the 1991 issue. Below, we briefly describe the unit in the Characteristics section, and we provide an overall rating for the unit, as well as an individual rating for each major test, in the Significant Test Results and Ratings section. Under each of these tests, we report on features that are unique to this laser or that surpassed our criteria and would likely be considered by hospitals during the selection process. We also report on limitations and deficiencies that failed to meet our criteria, that are hazardous, or that played a significant role in our rating for both the test category and the unit, as well as any modifications that the manufacturer has made to the unit to address our concerns. Some reliability problems that we encountered during testing are also discussed to provide users with some indication of the laser's performance and service requirements; however, this information was not used in determining the unit's rating. Also see the "Laser Technology Planning" and "Laser Use and Safety" Guidance Articles in this issue. PMID- 1428903 TI - Manufacturers' support policies. AB - Choosing an effective plan for supporting a medical device is critical to its safe use, cost-effectiveness, and longevity. Hospitals can choose from a variety of support providers, including manufacturers, third-party service vendors, or hospital clinical engineering (CE) departments. However, if the hospital plans to use a third-party service vendor or its own CE department to provide support, the manufacturer's cooperation or assistance will still be needed to implement the support plan effectively. Over the years, ECRI has received many comments from hospitals about the way in which manufacturers respond to their equipment support needs. We have learned that some manufacturers are not willing to assist third party service vendors or in-house service programs or do not always deliver the support they promise. Also, hospitals do not always consider their support needs before purchase, when they have the most leverage to negotiate flexible support arrangements. To help foster better equipment support and customer satisfaction, we polled manufacturers that have participated in recent Health Devices Evaluations to obtain detailed information about their policies toward manufacturers' contract, third-party, and in-house support. Ready access to this information will help hospitals evaluate whether manufacturers' support policies will meet their needs, and it will allow them to minimize problems by working with the manufacturer to negotiate optimal support arrangements during the purchase process. In this article, we briefly discuss the factors to consider when evaluating support alternatives and manufacturers' support policies. We also present the questions posed to each manufacturer on our Manufacturers' Support Policies Questionnaire, along with a summary of the responses that we received for each question.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1428904 TI - IV free-flow--still a cause for alarm. AB - A nurse's aide, in transferring a mother in labor to the delivery room, turned off the infusion pump delivering Pitocin, a drug administered intravenously to accelerate contractions. The aide removed the infusion set from the pump without first closing the manual clamp on the line. A free-flow infusion occurred, and the mother received nearly 35 times the prescribed amount of drug. The infant suffered organ damage and pneumonia and died four days later. Free-flow infusions can have tragic consequences when a potent drug is involved. Although other causes of overinfusion and free-flow exist, such incidents are typically associated with removing a disposable intravenous (IV) infusion set from an infusion device without first closing the manual clamp. We first raised this issue in our 1982 Evaluation "Infusion Controllers" and have emphatically and repeatedly addressed it in Health Devices and other ECRI publications. Yet, hospitals continue to report free-flow infusions, a problem that can be addressed by both hospitals and device manufacturers. In this article, we describe the causes of free-flow--both user error and device design; report numerous incidents, some resulting in death; and provide recommendations for reducing the likelihood that such problems will continue to occur. PMID- 1428905 TI - ECRINet--an overview. PMID- 1428906 TI - Improper sealing of Baxter Megafuge C1725-2 centrifuges. PMID- 1428907 TI - Bleeding around Kontron sheathed intra-aortic balloon hemostasis cuffs. PMID- 1428908 TI - Battery failures in a DCI EP-2 clinical stimulator. PMID- 1428909 TI - OR renovations and the use of isolated power and explosion-proof plugs. PMID- 1428910 TI - Low utilization of intra-aortic balloon pump. PMID- 1428911 TI - A bifunctional HBED-derivative for labeling of antibodies with 67Ga, 111In and 59Fe. Comparative biodistribution with 111In-DPTA and 131I-labeled antibodies in mice bearing antibody internalizing and non-internalizing tumors. AB - To investigate whether bifunctional ligands containing chelating structures other than EDTA and DTPA and metallic radiotracers other than 111In will reduce the non specific radioactivity uptake in the liver during immunoscintigraphy, we synthetized an isothiocyanato-substituted phenolic polyaminocarboxylic acid (HBED CI) for labeling of MAbs with 67Ga, 111In and 59Fe. Biodistribution of HBED-CI labeled MAbs was compared to that of 131I and 111In-DTPA labeled MAbs in nude mice bearing tumors, which differ with regard to intracellular internalization and catabolism of the corresponding MAb-antigen complex. In the liver a continuous radioactivity excretion for 67Ga-HBED-CI-labeled MAbs was observed with kinetics that parallel 131I clearance after administration of 131I-MAbs, while 111In-HBED-CI-labeling led to a constant 111In liver level quite similar to that of 111In-DTPA-MAbs. In tumors, 67Ga-HBED-CI-MAb uptake again paralleled that of 131I-MAbs, showing continuous accumulation in tumor tissues when internalization of the MAb-antigen complex was not involved. A much lower uptake, which peaked between 24 and 48 h, was found in the case of MAb-antigen internalization. 111In of 111In-HBED-CI- and 111In-DTPA-labeled MAbs continuously accumulated in both types of tumors. Compared with 111In-DTPA-MAbs, an improvement in tumor-to-liver ratios, due to the reduced liver radioactivity associated with 67Ga-HBED-CI-labeled MAbs, could only be obtained with non internalizing tumors. The time course of radioactivity distribution in the liver and in MAb-internalizing tumors after administration of 67Ga-HBED-CI-, 111In-HBED CI- and 111In-DTPA-labeled MAbs further indicates a dominating influence of the metallic radiotracer rather than the ligand on retention or excretion of radioactivity in MAb-catabolizing tissues. PMID- 1428912 TI - Attachment of 99mTc to lipid vesicles containing the lipophilic chelate dipalmitoylphosphatidylethanolamine-DTTA. AB - The binding of 99mTc to negatively-charged and neutral unilamellar lipid vesicles was investigated in the absence and presence of the ligand diethylenetriaminepentaacetic acid (DTPA) covalently attached to the headgroup of phosphatidylethanolamine at the surface of the membrane. Even in the absence of DTPA on the membrane surface, 99mTc reduced by Sn bound to the membrane surface but rapidly dissociated from the vesicles in the presence of plasma in vitro. When DTPA was present on the membrane surface, dissociation of 99mTc from the vesicle surface in plasma was much reduced. The dissociation of 99mTc from the surface of negatively-charged vesicles was less than for neutral vesicles in the absence of ligand but was markedly greater than for vesicles containing the ligand DTPA, suggesting that the binding of 99mTc to vesicles with surface attached DTPA could not be explained solely on the basis of the negative charge provided by the DTPA. In vitro experiments using 14C-labeled lipids as well as in vivo imaging studies indicated that dissociation of 99mTc from the surface of the vesicle did not arise predominantly because of lipid exchange with plasma components or due to cleavage of Tc-DTPA from the vesicle surface. For vesicles with surface-attached DTPA, 99mTc dissociation from the vesicle surface in plasma was further reduced by addition of the antioxidant ascorbate. PMID- 1428913 TI - Evaluation of S-[11C]citalopram as a radioligand for in vivo labelling of 5 hydroxytryptamine uptake sites. AB - The biologically active S-enantiomer of [N-methyl-11C]citalopram was evaluated as a radioligand for in vivo labelling of the 5-hydroxytryptamine uptake site in brain, using ex vivo tissue counting in rats and positron emission tomography in man. In rats, the maximal signal for total versus non-specific binding was approx. 2 at 60-120 min after radioligand injection. Subsequent studies in man failed to identify a specific signal over a 90 min scanning period, due to prolonged retention of non-specific label. PMID- 1428914 TI - Ligands and tracers for PET studies of the 5-HT system--current status. AB - The status of the radiochemical development and biological evaluation of radioligands and tracers for PET studies of the serotonergic system is reviewed, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies of central 5-HT2 receptors, namely [18F]setoperone and [18F]altanserin. Though, it has not proved possible to recommend tracers or radioligands for the study of other aspects of serotonergic system, prospects for future radiochemical development are indicated, especially for developing radioligands for the 5-HT re-uptake site, and for the 5-HT1 and 5-HT3 receptors. PMID- 1428915 TI - (S)- and (R)-[11C]nicotine and the metabolite (R/S)-[11C]cotinine. Preparation, metabolite studies and in vivo distribution in the human brain using PET. AB - In order to investigate [11C]nicotine binding and metabolism in the living human brain by PET, routine protocols were developed for the preparation and purification of (S)- and (R)-[11C]nicotine and the metabolite (R/S) [11C]cotinine. (S)- and (R)-[11C]nicotine were prepared by N-methylation with [11C]methyl iodide of the appropriate secondary amine, which was liberated in situ by 2,2,6,6,-tetramethylpiperidine (TMP) from its corresponding biscamsylate salt. (R/S)-[11C]Cotinine was prepared by N-methylation of the amide precursor using tetrabutylammonium hydroxide as a phase transfer catalyst. Straight-phase semipreparative HPLC was in all purifications found to be superior to reversed phase since the contamination by the norcompounds was eliminated. Reaction in acetonitrile for both (S)- and (R)-[11C]nicotine (5 min, 130 degrees C) and (R/S) [11C]cotinine (1 min, 80 degrees C) with subsequent straight-phase HPLC purification resulted in 35-45% radiochemical yield (from EOB and decay corrected) with a total synthesis time of 30-35 min, a specific radioactivity of 1000-1500 Ci/mmol (37-55 GBq/mumol, EOS) and a radiochemical purity > 99%. The uptake and distribution of these tracers in the human brain was studied in healthy volunteers by PET. The metabolite (R/S)-[11C]cotinine did not cross the blood-brain barrier to any significant degree. The amount of the total radioactivity representing (S)-[11C]nicotine measured in plasma by HPLC was 75% at 4 min and 25% at 50 min. PMID- 1428916 TI - Photoreactive 111In-cyclodextrin inclusion complex: a new heterobifunctional reagent for antibody labeling. AB - The compound of interest, N-5-azido-2-nitrobenzoylaminomethyl-111In-acetylacetone alpha-cycl odextrin (CD) (V) was synthesized by the selective tosylation of alpha CD to form 6-tosyl-6-deoxy-CD, which was then reacted with NaN3 to form 6-azido-6 deoxy-CD (II). This was followed by catalytic hydrogenation to yield III. Compound III and 111In-acetylacetone were mixed to form an inclusion complex, which was then reacted with N-5-azido-2-nitrobenzoyloxysuccinimide to yield compound V. Anti-melanoma MAbTP41.2 was added to compound V, followed by immediate photoreactivation labeling by u.v. light at 320 nm. The final product VI was purified from a Sephadex G-50 column. 111In-DTPA-MAbTP41.2 was also prepared as a control. Immunoreactivity via the cell-binding assay of VI was 87%, compared with 57% by the BADTPA method. Biodistribution in non-tumor rats yielded a liver concentration in %ID/g of 3.5, 1.7 and 1.0 for compound VI, compared to the 5.5, 5.2 and 3.1 for the BADTPA compound, at 4, 24 and 48 h post-injection, respectively. PMID- 1428917 TI - [The entrapment syndrome of the popliteal artery: diagnosis, therapy, results]. AB - The popliteal artery entrapment syndrome is caused by an anatomical anomaly in the popliteal fossa. Mostly the popliteal artery is compressed by a faulty insertion of the medial head of the gastrocnemius muscle. The main symptom is an intermittent claudication at an early age. We review our experience with four typical cases. All patients were examined because of a unilateral sudden claudication in the calf at ages between 23 and 43 years. In two patients we could find angiographically a typical stenosis, in two others a complete occlusion of the popliteal artery. Additionally a female patient showed a 6 x 8 cm poststenotic aneurysm in the popliteal fossa. Therapeutically we restored the flow of the artery on two patients by dividing the compressing gastrocnemius muscle. As a late complication two years after the first operation one of these patients had an occlusion of popliteal artery which was bypassed by a popliteo crural vein graft. On two patients we primary inserted a vein graft. All patients were checked 6 months till 5 years after the first operation by duplex scanning, by measurement of pressure at the ankle and by pulse volume recording at the big toe. All our postoperative examinations demonstrate patency of the repairs and the patients have very few problems. PMID- 1428918 TI - [Axillo-femoral bypass: indications and results]. AB - Axillofemoral bypass grafting is an accepted method for the treatment of vascular insufficiency of the lower limb. It is especially useful in high risk patients whose conditions preclude aortofemoral bypass grafting. The goal of our study is to evaluate whether the benefit of this operation outweigh the potential risks in the age group "sixty-plus". We performed 23 axillofemoral bypass grafting procedures (axillofemoral in 20, axillobifemoral in 3 cases) mainly be mean of 8 mm Dacrom prosthesis. The 30-day operative mortality rate was 8.7% and the cumulative 5-year patient survival rate was 52.2%. Overall the 1- and 5-year life table patency rate were 80% and 64%, respectively. The cumulative limb salvage was 90% and 72% at 1 and 5 years. We obtained an average reduction in Fontaine classification of 2 stages in the first year and 1.3 stages after 5 years. The comparison of the cumulative survival rate with the limb salvage rate indicates that advanced age should not be considered a contraindication to performing an axillofemoral bypass graft. The reduction in Fontaine stage means a remarkable improvement in quality of life. PMID- 1428919 TI - [A new intraluminal endarterectomy instrument]. AB - In 40 human cadaver arteries endarterectomy was performed using a new intravascular device. The system and technique are described. According to our preliminary laboratory experiences the new device proofed to be save and effective. It will allow us to approach more complex lesions not ideal for balloon angioplasty. Clinical investigations will be performed in the near future. PMID- 1428920 TI - [Anomalies of immunoglobulin synthesis in vitro in surgical patients]. AB - It is known that blood mononuclear cells from surgical patients produce large amounts of IgG in vitro, and that this synthesis is not increased by pokeweed mitogen stimulation. The objective of the present study was to determine if this abnormal pattern of IgG synthesis extended to other immunoglobulin classes. Patients were stratified according to delayed type hypersensitivity as reactive (induration > 5 mm to > one skin test antigen), or anergic (no response). Healthy laboratory personnel were studied as controls. Mononuclear cells were cultured for 10 days, without or with pokeweed mitogen. IgG, IgM, and IgA in supernatant was measured using a competitive solid phase radioimmunoassay. Unstimulated IgG and IgA synthesis was increased in surgical patients, especially in those with reduced delayed type hypersensitivity responses. IgM synthesis was normal or low. With mitogen stimulation, normal increases in IgG synthesis were seen in control and reactive subjects. In anergic patients, IgG was not increased by pokeweed mitogen. For IgM, mitogen stimulation increased synthesis but to a lesser degree in patients than in controls. For IgA, synthesis was increased by mitogen stimulation in all groups. In conclusion, surgical patients show abnormalities in the pattern of spontaneous and mitogen stimulated immunoglobulin synthesis. The pattern varies for each isotype. B cell activation is present in surgical patients, especially those with reduced delayed type hypersensitivity. This suggests either recent antigenic stimulation, or non-antigen specific dysregulation of the B cell system in surgical patients. PMID- 1428921 TI - [Eosinophilic gastroenteritis: two case reports]. AB - Eosinophilic gastroenteritis is a rare lesion that may present a diagnostic problem to the surgeon. It may be confused with a malignant tumor because it often presents with intestinal obstruction. We treated two cases at the Hopital de zone de Morges. In one case the lesion was in the gastric antrum and in the other the ascending colon. Only 27 cases of colonic eosinophilic gastritis are described in the medical literature. PMID- 1428923 TI - [Massive hemorrhage from presacral veins during resection of the rectum]. AB - During the last 53 abdominoperineal amputations of the rectum for carcinoma, we had to control 5 massive hemorrhages. 4 of which were due to a lesion of the presacral venous plexus and caused a mean blood-loss of 4750 ml. During a "normal" Mile's operation our 49 other patients lost an average of 1750 ml (median 1200 ml) of blood. The negative effects of this type of complication and the following need for massive transfusion is not only local, circulatory and pulmonary, but also due to the immunodepressive effects of massive transfusion. We describe the different methods of control of these hemorrhages and insist on the advantage of using sterilised metallic thumbtacks, a method which was described 1984 by doctor Wang Qinyao of Shanghai. PMID- 1428922 TI - [Meckel's diverticulum: surgical complications]. AB - A 20-year (1971-1990) retrospective follow-up of all patients with a Meckel diverticulum (MD) out of the Kantonsspital and St. Claraspital Basel is reported. There were 57 men and 34 women with a mean age of 46.7 years (14-89). 60.4% of the cases were occasional findings, 39.6% were symptomatic MD. During the same period of time 5000 appendectomies were performed (ratio diverticulectomy to appendectomy was 1:50). 38.5% of the resections of MD were done when an acute appendicitis was supposed. In one third of the cases the MD was responsible for the symptomatology. Histological findings were 13% unspecific inflammation, 10% perforation, 9.8% ectopic tissue, 6.5% bleeding and 4.3% tumors. 8 out of 36 patients with pathological findings showed postoperative complications (21.6%), the mortality rate was 8.1%. In 55% resected MD without any additional histological findings only one complication (postoperative ileus) (1.9%) was found; mortality was zero per cent. The analysis of these data shows that complications of MD does not only appear in young patients. Complications occur more often in patients with MD with additional ectopy. We recommend the resection of an incidentally discovered Meckel diverticulum. PMID- 1428924 TI - [Severe necrotizing fasciitis]. AB - The pathophysiology of necrotizing fasciitis remains unclear in patients with no apparent immunologic disorders. Between 1987 and 1990 we treated six patients with necrotizing fascitis and septic-toxic multiple organ failure, three patients survived. The mean age was 38 years (25-62). In all patients the primary bacteriological examination revealed streptococcus. Between the first symptoms and an adequate therapy were 4 days in surviving patients and 7 days in patients who died. Four patients showed spread of the gangrene into the adjacent tissue: muscles (n = 3), bowel (n = 2), mediastinum (n = 1). Adequate debridement was not possible or not performed in patients with spread into the abdominal cavity or the mediastinum. These patients did not survive. The duration of intensive care treatment in surviving patients were 14 to 78 days. We conclude that survival of patients with severe necrotizing fasciitis is influenced by the delay before adequate treatment, the localisation of the gangrene and intensive care facilities. PMID- 1428925 TI - [Hernia of the surgical scar--predisposition or inadequate suture technique?]. PMID- 1428926 TI - Detection of aneuploid subpopulations in colon cancer biopsies by cultivation in vitro prior to flow cytometric analysis. AB - Flow cytometry offers a relatively simple method to determine the DNA content of colorectal cancers. However, the technique can not discover minor changes in karyotype which may characterize near-diploid tumors, nor will it detect very small populations of aneuploid cells. In an attempt to improve the detection of such cells, we incubated biopsy material prior to analysis. This method revealed an aneuploid subpopulation in one of two biopsies studied. This simple protocol may ultimately lead to a more accurate assessment of the ploidy in colon cancer. PMID- 1428927 TI - [Callus distraction in traumatology: concepts and indications]. AB - The understanding of the conditions under which bone and soft tissue can be regenerated by distraction has opened a new era in the field of limb reconstruction. Success in lengthening for posttraumatic limb length discrepancy has led to different applications of the distraction techniques. We present an overview of the clinical new possibilities, the strategy, the techniques and the complications using the distraction technique in the trauma patient. The optimal biologic method (limb distraction after resection or callus distraction by a transport technique) and the optimal fixation devices depend on the indication (local aspect, polytrauma, patient, motivation). PMID- 1428928 TI - [Definitive surgery in complicated gastroduodenal ulcers]. AB - Indications for surgical therapy in uncomplicated peptic ulcer disease have decreased considerably since the introduction of H2-receptor blocking drugs and more recently omeprazole. On the other side, the number of acute complications such as perforation or hemorrhage has remained nearly constant. The recent literature seems to indicate that the pattern of patients presenting with complications has changed and that the number of acute ulcers has increased. In a review of 283 patients, we found 150 perforated ulcers (PU) and 133 bleeding ulcers (BU). Almost all the patients with PU and 70% of the patients with BU have been treated operatively. The mortality is 14.3% and 12.5%, respectively. The vast majority of our patients have chronic ulcers, and only 7% have acute or subacute lesions confirmed by histologic examination. Based on our experience and the literature, we propose a therapeutic algorythm for these two conditions. PMID- 1428929 TI - [Central venous access for total parenteral nutrition: choice of catheter and venous access]. PMID- 1428930 TI - [Technique and organization of heart removal from the multi-organ donor]. AB - The orthotopic heart transplantation is an accepted treatment for terminal cardiac disease. The technique of heart procurement and preservation is explained and the primary graft function in 108 subsequent heart transplantations is assessed. The mean ischemia time is 41 +/- 10 min in local, 98 +/- 19 min in distant (< 100 km) and 114 +/- 16 min in distant (> 100 km) organ procurement. Our method of preservation consists of cold cardioplegic arrest with potassium (30 mEq/L) cardioplegic solution. The incidence of the indication for high dose katecholamine-treatment after surgery and the maximal creatininekinase levels rose with ischemia time. All hearts recovered within a few days and the stay in the intensive care unit was not prolonged. We conclude that the heart preservation with cold cardioplegic arrest results in a good primary graft function. It is important to keep the ischemia time as short as possible. PMID- 1428931 TI - [Bursitis iliopectinea--a rare differential diagnosis of painful inguinal swelling]. AB - The syndrome of iliopectineal bursitis is an important differential diagnosis of a painful swelling in the inguinal region. Symptoms are local swelling and pain, radiation of pain along the femoral nerve, troubles of arterial or venous circulation and even dysuria or dysmenorrhoea in case the bursa penetrates into the pelvis. The diagnosis is established by conventional radiology (signs of osteoarthritis as one of the pathogenetic reasons), ultrasound (liquid mass lateral to the femoral vessels), punction (clear fluid, eventually synovial cells), contrast injection (dimension of the bursa and communication to the hip joint) and computed tomography (dimension, relation to hip and vessels). The treatment is the excision of the bursa, if conservative therapy is not successful. The excision requires tedious, cautious dissection because of the important structures adjacent and a possible communication to the hip joint must be eradicated. PMID- 1428932 TI - [Experimental atrophy/hypertrophy complex of the liver after portal and/or biliary ligation in the rat]. AB - Patients with lobar or segmental, benign or malignant strictures of the biliary tree (with or without impairment of the portal blood flow) show a considerable atrophy of the involved area of the liver with a compensatory hypertrophy/hyperplasia of the remaining non affected liver. To investigate the importance of the biliary and portal obstruction for the development of this process, we used a rat model, with selective biliary and/or portal ligation of the anterior liver lobes (two thirds of the liver mass). Weight measurements, morphometry, functional scintigraphy (Hepatoiodida-scan) and blood enzyme analyses were done immediately postoperatively, at 30 hours and 4, 8 and 28 days after the operation. The major findings were: 1. 28 days after biliary and/or portal ligation there was no difference between the body weight of the four groups, all ligated animals having compensated for an initial greater percentage body-weight loss. 2. Total liver weight remained constant, while atrophy and hypertrophy/hyperplasia occurred although a progressive derangement of liver morphology was observed during that time. 3. A severe atrophy-hypertrophy-complex (AHC) developed after selective portal ligation, which in our experiment did not appear after selective biliary ligation. 4. Morphometrical changes after selective biliary ligation were reversible, whereas in liver lobes with selective portal ligation a progressive parenchymal destruction and involution with subsequent impairment of hepatic function of the concerned lobe was observed. PMID- 1428933 TI - [Acute abdomen in abdominal wall hemorrhage in anticoagulation]. AB - 10 patients with a history of systemic anticoagulation presented with an acute abdomen which proved to be due to a rectus sheath hematoma. Four patients gave a history of antecedent trauma. The prothrombin time was prolonged beyond the therapeutic range in 8 patients and therapeutic in two. The diagnosis of rectus sheath hematoma was made by non-invasive imaging (sonography [n = 8], CT-scan) in 9 patients and by operative exploration in one. 8 patients were treated non operatively and one patient required a delayed evacuation of the infected hematoma. One patient died from myocardial infarction. We conclude that a careful history, physical examination and prothrombin time, in combination with radiologic evaluation (sonography, CT-scan) can confirm the suspected diagnosis of rectus sheath hematoma. It is important to think of this specific hemorrhagic complication induced by anticoagulation to prevent unnecessary surgery. PMID- 1428934 TI - [Necrosis of the terminal ileum after drug poisoning. Case report]. AB - In an attempt to commit suicide, a 32-year-old women swallowed a vast amount of psychiatric drugs, i.e. tranquilizers, amphetamines, hynotic and antidepressant agents. By intensive care, using high doses of catecholamines and appropriate antidota, satisfactory circulation and oxygenation could be maintained. 3 days after admission a peritonitis became apparent. A 50 cm long section of the distal ileum was found to be completely necrotic and had to be resected. However, circulation of the correspondent mesenterium was not disturbed at all. A drug induced non-occlusive intestinal ischemia was postulated to be the pathophysiological mechanism of intestinal necrosis. Non-occlusive intestinal ischemia is rare; it has been reported in young adults intoxicated by cocaine or phenobarbital, in children with high overdosage of iron compounds, in elderly individuals suffering from low-output congestive heart disease and in patients treated with digitalis drugs, with or with or without overdosage. PMID- 1428936 TI - [E. Delorme correction of rectal prolapse]. AB - Rectal prolapse is a distressing condition. Among the multiple corrections described, the perineal approach has generally been abandoned. However, Delorme's procedure is a good, simple and efficient intervention with a low morbidity for certain elderly selected patients. The purpose of this paper is to recall the details of this technique and review its results. PMID- 1428935 TI - [Gardner syndrome: possibility of early detection of carriers by examination of the ocular fundus?]. AB - Through indirect ophthalmoscopic examination it was possible to analyse three families originated from the same Swiss alpine valley (Poschiavo) and carrying Gardner syndrome (SdG) to check if their members with SdG were presenting hypertrophic changes of the retinal epithelium which is supposed to be an early symptom of that syndrome. This lesion was found to be present only in two out of 11 patients (18%) with at least one symptom of SdG. Because of its lacking sensitivity, ophthalmoscopic examination is not able to substitute colonoscopy as a valid screening method to find out which members of a SdG-family are at risk to develop colonic poliposis and cancer. PMID- 1428937 TI - [Radiation-sparing intramedullary nailing with a radiolucent drilling system]. AB - The indications for intramedullary fixation of tibial and femoral shaft fractures markedly increased by the introduction of interlocking techniques. Distal interlocking however remains a major problem although a variety of different aiming devices have been proposed. To reduce the radiation exposure both of the surgeon and the patient the AO has produced a radiolucent drive which allows easy aiming and drilling with a minimum of X-ray exposure. PMID- 1428938 TI - [Technique of intraoperative laparoscopic cholangiography]. AB - Since laparoscopic cholecystectomy has been established at our institution, the routine use of intraoperative cholangiography was abandoned but preoperative intravenous cholangiography and sonography are mandatory. However, these investigations are not always conclusive and in some cases not applicable. We have therefore started to use selective intraoperative laparoscopic cholangiography for laparoscopic cholecystectomy. Our technique and the materials required for this peroperative investigation are described in the present article. PMID- 1428939 TI - [General aspects of kidney removal from donors with cardiovascular arrest]. AB - The increasing list of patients waiting for an organ transplantation shows clearly the shortage of donor organs at disposal. This shortage is particularly high in the field of kidney allotransplantation. As the nephrectomy in non-heart beating (NHB) donor is technically practicable in most of our hospitals, the aim of this contribution is to pass on further informations about the nephrectomy to those surgeons who are interested in the procedure. The first part of the paper explains the different facts of the end stage renal disease in Switzerland and of transplantation activity. We focus then on the conditions and preparations of the nephrectomy in NHB donor, the exact technique of the operation and the organ perfusion. As it is shown by different studies, the long-term results of NHB donor kidneys are good. The nephrectomy in NHB donor is an effective method to solve kidney shortage. PMID- 1428940 TI - [High velocity water jet dissection in liver surgery]. PMID- 1428941 TI - HB Al-Ain Abu Dhabi [alpha 18(A16)Gly----Asp]: a new hemoglobin variant discovered in an Emiratee family. AB - During a routine program of hemoglobin screening performed in the United Arab Emirates, we observed an electrophoretically fast-moving variant in a 9-month-old girl and in several members of her family. The structural determination, performed by reversed phase high performance liquid chromatography and amino acid sequencing, revealed a new variant that we named Hb Al-Ain Abu Dhabi [alpha 18(A16) Gly----Asp]. Its functional properties were normal. PMID- 1428942 TI - Rapid molecular diagnosis of hemoglobin variants by RT-PCR of reticulocyte mRNA and direct sequencing. AB - We have developed a rapid and simple approach for the molecular characterization of hemoglobin variants by a one-step reverse transcription-polymerase chain reaction of reticulocyte mRNA and direct sequencing of the product. This method can selectively amplify the alpha 1- or alpha 2-globin gene or the beta-globin gene transcript. The amino acid substitution of Hb G-Taichung is due to a G----C mutation at codon 74 of the alpha 1-globin gene, that of Hb J-Meinung to a G----A substitution at codon 56 of the beta-globin gene, and that of Hb Kaohsiung (or New York) to a T----A substitution at codon 113 of the beta-globin gene. The amplified segment encompassed the sequence from upstream of the initial codon behind the Cap site to downstream of the terminal codon before the polyadenylation addition signal. Hence, all hemoglobin variants should be able to be characterized by this approach. PMID- 1428943 TI - The -87 (C----A) beta(+)-thalassemia mutation in a black family. PMID- 1428944 TI - Hb H disease in association with the silent beta chain variant Hb Hamilton or alpha 2 beta 2(11)(A8)Val----Ile. PMID- 1428945 TI - A case of -(4.2)alpha T/-(4.2) alpha Q in combination with a beta zero thalassemia homozygosity found in a family of the Zhuang nationality in china. PMID- 1428946 TI - Hb Shelby [alpha 2 beta 2(131)(H9)Gln----Lys]-beta zero-thalassemia [codon 15 (TGG----TGA)] identified by DNA sequencing. PMID- 1428947 TI - Association of Hb Hope [beta 136(H14)Gly----Asp] and alpha-thalassemia-2 (3.7 Kb deletion) causing severe microcytic anemia. PMID- 1428948 TI - Alpha-globin genotypes in a Spanish population. PMID- 1428949 TI - Hb H disease and mild mental retardation in a black girl with a Hb S heterozygosity. PMID- 1428950 TI - Hb Yuda or alpha 130(H13)Ala----Asp; a new alpha chain variant with low oxygen affinity. PMID- 1428952 TI - Estimation of changes in genetic parameters in selected lines of mice using REML with an animal model. 1. Lean mass. AB - Analysis was undertaken using Restricted Maximum Likelihood (REML) with an animal model of the results of selection for 20 generations for predicted lean mass in 10-week-old male mice. There were three replicates, each comprising high, low and unselected control lines. The overall estimates of heritability (h2) and common environmental correlations (c2) from results of the first seven generations were 0.51 +/- 0.03 and 0.21 +/- 0.01, respectively. Analyses of data from different lines and different numbers of generations were undertaken but with all pedigrees and data included, which enabled inferences to be drawn on changes in variance that were not due simply to inbreeding or short-term effects of selection. Estimates of h2 were lower in selected lines than the control, increasingly so in later generations, indicating departure from the infinitesimal model assumption of unlinked additive genes each of very small effect. In addition, values of c2 became higher in high than in control or low selected lines. PMID- 1428951 TI - Hb Ethiopia or alpha 2(140)(HC2)Tyr----His beta 2. PMID- 1428953 TI - Estimation of changes in genetic parameters in selected lines of mice using REML with an animal model. 2. Body weight, body composition and litter size. AB - Restricted Maximum Likelihood (REML) with an animal model was used to estimate genetic parameters of body weight, body consumption and litter size of lines of mice selected for 20 generations on an index of lean mass at 10 weeks in males, highly correlated with body weight, and for a further 18 generations on body weight at 10 weeks in males and females. Univariate and multivariate estimates of heritability were about 0.5 and those of common environment correlations were about 0.25 for both body weight and composition. Body weight and fat pad weight had genetic and phenotypic correlations of about 0.5. The heritability estimate of litter size was about 0.15 from univariate analysis, rather lower from multivariate, and the estimate of its genetic correlation with body weight was about 0.25. There were reductions in heritability of both body weight and litter size in later generations, even though full pedigrees were fitted and inferences made to the base population, but a plateau in response to selection for increased body weight could not be explained by a complete attenuation of genetic variance. PMID- 1428954 TI - Genetic determinism of the cellular immune reaction in Drosophila melanogaster. AB - Larvae of Drosophila melanogaster produce a haemocytic reaction against eggs of the parasitoid Leptopilina boulardi, which leads to the formation of a multicellular capsule surrounding the foreign object. Melanization resulting from the conversion of phenol to o-quinones frequently accompanies the cellular reaction. Although various cytological and biochemical aspects of this reaction have been investigated, very little is known about genetic determinism of the insect immune response. The heredity of the capacity to encapsulate was analysed by comparing 16 reciprocal crosses made using inbred resistant and susceptible parental strains. We conclude that differences in the encapsulation capacity of D. melanogaster are inherited autosomally, with the reactive phenotype showing complete dominance over the non-reactive one. There were neither sex-linked nor maternal effects. The results of all crosses suggest a single major segregating locus with two alleles and complete dominance of the resistant allele, with cytoplasmic factors and minor modifying genes acting on the major locus. PMID- 1428955 TI - Genetic basis for female receptivity in Drosophila melanogaster: a diallel study. AB - Receptivity of sexually mature, virgin females, measured as the time to copulation, has been investigated. Two independent 5 x 5 diallel crosses were carried out, each one with a different male tester genotype. Interactions between male and female genotypes were detected because some lines appeared as dominant in one diallel and recessive in the other. The overall picture emerging from the analyses shows a genetic system for female receptivity characterized by additive genes, with dominance for high receptivity in one of the diallel crosses. This remarkable additive component does not support the action of natural selection favouring females with extreme values of receptivity, rather, the lack of intrasexual female competition for mates is suggested. PMID- 1428956 TI - Loss of a paternal chromosome causes developmental anomalies among Drosophila hybrids. AB - Hybrids between Drosophila virilis and D. lummei suffer from developmental anomalies. Previous reports also suggest that these hybrids lose the D. lummei sixth chromosome early in development. Genetic and cytological data presented here confirm the loss of the microchromosome from both the soma and the germ-line of these hybrids and provide strong evidence that this loss causes the hybrid developmental anomalies. PMID- 1428957 TI - vestigial suppressor genes and resistance to aminopterin in Drosophila melanogaster. AB - We have shown that the vestigial (vg) mutant of D. melanogaster has a perturbed nucleotide metabolism compared to various wild-type strains. The mutant is particularly spontaneously resistant to aminopterin. The resistance seems to correlate with an increase in dihydrofolate reductase (DHFR) activity and quantity. The DHRF is a target enzyme of aminopterin. Our results suggest that the vg+ gene could be a regulatory gene acting on the DHFR gene. The wing mutant phenotype being due to a decrease in the thymidylate pool (dTMP) (Silber et al., 1989). In order to understand better the action of the mutant gene on nucleotide metabolism, we have induced suppressor genes of the mutant phenotype by mutagenesis with ethyl methanesulfonate (EMS) and bromouridine (BUR). The suppressor strains obtained display a phenotype intermediate between wild-type and vg phenotype. The action of three independent suppressor genes on eight parameters of nucleotide metabolism is reported here [three enzyme activities, resistance to aminopterin and to fluorodeoxyuridine (FUdR), auxotrophy test and the ability to use exogenous thymidine and uridine]. In comparison to the original vg strain, major changes for the parameters tested are observed. The most striking effects are obtained with the vgBUR27 strain, which is highly sensitive to aminopterin and to fluorodeoxyuridine and didplas the highest thymidine kinase (TK) and DHFR activities within the strains tested. The potential actions of suppressor genes on the vg mutant are discussed. PMID- 1428958 TI - Therapeutic options for localized carcinoma of the prostate: the role of external beam radiation therapy. AB - During the last three decades the use of ionizing radiation, both external beam radiotherapy and interstitial radionuclide implant (brachytherapy), has greatly increased for the treatment of cancer of the prostate. The increased use of radiation therapy is in part due to the technological advance of high-energy megavoltage units as well as the steadily improving long-term results of radiotherapy. Because of the comparable tumor control rates, patients with early stage prostate cancer have several therapeutic options for curative treatment including radical prostatectomy, external beam radiation therapy, and interstitial brachytherapy. The role of external beam radiotherapy is discussed in terms of the primary management of early and locally advanced prostate cancers as well as the treatment of residual or recurrent disease after prostatectomy. A new approach combines antimitotic chemotherapeutic agents and radiation therapy for the treatment of locally advanced cancers of the prostate. PMID- 1428959 TI - Radical surgery in the treatment of localized carcinoma of the prostate. AB - New methods of early detection combined with recent advances in surgical techniques have resulted in more patients undergoing radical surgery for treatment of localized carcinoma of the prostate. Over 350 radical prostatectomies have been performed by our group since January 1987. We review the role of radical prostatectomy in the treatment of prostate cancer and our experience with 100 patients undergoing radical retropubic prostatectomy since the advent of nerve-sparing techniques to preserve potency. PMID- 1428961 TI - Maximal androgen ablation: a review. AB - Primary management of advanced (stage D) adenocarcinoma of the prostate is androgen ablation. Since this principle was discovered in the early 1940s, therapeutic alternatives and "progress" have centered around different ways to obtain castrate levels of androgens. The role of adrenal androgens in supporting prostate or prostatic cancer growth has been debated for decades and until recently was believed to be minimal. In the 1980s the concept of maximum androgen suppression, involving both the testes and adrenal glands, was reintroduced with some investigators claiming exceptional results. We review studies that have examined this concept, with emphasis on the largest trial which was carried out by the National Cancer Institute. PMID- 1428960 TI - Management of impotence after treatment of carcinoma of the prostate. AB - Impotence commonly occurs as a result of treatment of carcinoma of the prostate. We review the etiology, evaluation, and treatment options available for these patients as well as our experience with fifty prostate cancer patients who underwent placement of penile prostheses. Several excellent alternatives are available for patients with impotence resulting from treatment of carcinoma of the prostate. PMID- 1428962 TI - Advances in therapy of female stress incontinence. PMID- 1428964 TI - Cerebral oxygen extraction during severe viral encephalitis. AB - Viral encephalitis can cause devastating neurologic injury. Little is known about cerebral hemodynamics and metabolism in this condition. We report two patients with severe encephalitis, one proven and the other suspected to be due to herpes simplex, in whom the global cerebral oxygen extraction ratio (OER) and carbon dioxide (CO2) responsiveness was assessed. OER was low in both patients throughout the acute period. CO2 responsiveness was present initially in both and disappeared later in the more severely affected child. These cases demonstrate that cerebral hyperemia occurs in severe viral encephalitis and that hyperventilation can effectively reduce the intracranial pressure. PMID- 1428963 TI - Megakaryoblastic termination of myeloproliferative disorders. AB - Megakaryoblastic termination of myeloproliferative disorders is rare. The morphology of megakaryoblastic transformation can be subtle and is often mistaken for myeloid or lymphoid proliferations. Previously reported observations suggest a relatively poor prognosis for this category of patients, making precise diagnosis imperative. A multifaceted approach using morphology, ultrastructure, cytochemistry, and immunological membrane analysis may be helpful. We present two cases of myeloproliferative disorder with aggressive megakaryoblastic phases (myelofibrosis with agnogenic myeloid metaplasia and chronic myeloid leukemia with blast crisis). The clinical course is described and the results of the morphological, cytochemical, ultrastructural, and cytogenetic studies of both cases are presented. In addition, immunochemical studies (flow cytometry) and platelet function studies (aggregation, beta-thromboglobulin, and platelet factor IV release) were done for one of these patients. PMID- 1428965 TI - Federal, state, and local partnerships in providing primary care: one urban health department's endeavor with a state university medical center. AB - We describe how the federal government, the City of Chicago, and the State of Illinois worked together to increase the availability and accessibility of health care services on Chicago's underserved west side by reopening a bankrupt, federally-funded community health center. The federal government made the building available to the City which then contracted with a state university medical center to be the provider of services. This partnering has allowed the Chicago Department of Health to offer services in a previously underserved area. The University has gained an opportunity for community-based primary care teaching, as well as community relations. Patients have increased access to a wide variety of specialty and inpatient care. If public health providers are to be successful in this financial climate, they must look to new partners and new ways of delivering services to increase availability of services at a time when they are greatly needed. PMID- 1428966 TI - The emerging role of HTLV-I/II and HIV-1 among intravenous drug users in Detroit. AB - During 1987-1988, a seroprevalence study of the human immunodeficiency virus (HIV 1) and the human T-cell lymphoma/leukemia virus (HTLV-I/II) was performed among Detroit intravenous drug users unaffiliated with substance abuse programs. Seroprevalence data along with patient demographic information were compared to a similar study performed in 1985-1986. In the earlier study, 12 (12.5%) of 96 individuals tested positive for HIV-1. Of the 74 available negative samples retested in 1987-1988 for retroviruses, 7 (9.5%) tested positive for HTLV-I/II. Thus, the overall retroviral (HIV-1, HTLV-I/II) seropositive rate for 1985-1986 was 22%. In 1987-1988, 11 (15.7%) of 70 individuals tested positive for HIV-1 and 7 (10%) tested positive for HTLV-I/II. Concomitant infection with both viruses was found in 2 (2.9%) of the 70 individuals. Thus, retrovirus seroprevalence in 1987-1988 was 22.9%. In 1987-1988, significant differences between the retroviral positive group and the retroviral-negative group consisted of intravenous drug use greater than 16 years (P = 0.059) for an odds ratio of 3.80 (CI 1.12-12.89) and sex with female prostitutes (P = 0.029) for an odds ratio of 5.38 (CI 1.38 20.95). PMID- 1428968 TI - Interpretation of the pattern in rate ratios across strata. AB - The pattern in the ratio of disease rates over strata is a summary statistic used to describe the changing risk of disease in one group relative to another. While patterns of the ratios of disease rates over strata appear to correspond to specific changes in disease rates, plots of the disease rates over strata seem to contradict the information yielded by the ratios. For example, if disease rates from populations A and B have identical rates of decline (parallel lines), the difference in the rates (A-B) at each strata remains constant, while the ratio of the rates (A/B) increases over strata. Through simple algebraic manipulation, one can show that the pattern of the rate ratio is a function of the rate difference relative to the endemic disease rate. Thus, rather than describing the behavior of the disease rates, ratio patterns reflect the importance of exposure relative to the disease rate in the unexposed population. PMID- 1428967 TI - Primary papillary serous carcinoma of the peritoneum: a case of complete remission of bulky peritoneal disease after chemotherapy. AB - Peritoneal papillary serous carcinoma is a rare tumor that involves the surface of the pelvic and/or abdominal peritoneum. Long-term survival among patients with this tumor has been rare. Most patients with this cancer have been treated with debulking surgery and postoperative chemotherapy. A case of incompletely resected peritoneal papillary serous carcinoma with a complete response to cisplatin-based chemotherapy is reported. Subsequent laparotomy revealed no residual tumor. This case suggests that primary chemotherapy may be successful in treating unresectable primary papillary serous tumors of the peritoneum. PMID- 1428969 TI - Presentation and evaluation of patients with epidermoid head and neck cancers. AB - Epidermoid cancer of the head and neck occurs most frequently in individuals with predisposing factors for neoplastic development. Primarily these include exposure to smoking and alcohol, although other predisposing factors may be present. Site specific symptoms along with a history of predisposing environmental exposure can direct physicians to suspect head and neck cancer. Endoscopy and ancillary testing are performed for tumor staging and subsequent treatment planning. PMID- 1428970 TI - The why and wherefore of fructosamine. AB - GH and FA are useful monitors in the care of diabetic patients. For most situations, GH is the preferred test and should be routinely monitored. FA should be reserved for exceptional situations in which blood glucose control over one to two weeks must be assessed or in patients with a hemoglobinopathy. Patients with diabetes should be advised of their present GH level and the preferred goal. PMID- 1428971 TI - Public health care delivery in five U.S. municipalities: lessons and implications. AB - Increasing pressures on private and public hospitals have necessitated a reassessment of urban health care delivery. Patients left unserved by stressed private hospitals have placed a greater burden on public institutions, which themselves are often old, underfunded, and in danger of closure. As policy analysts consider remedies, primary care in community-based settings has reemerged as an important component of planning. We present results of a comparative analysis of five public health care delivery systems (Boston, Dallas, Denver, Milwaukee, and Seattle), reflecting their economic, political, and cultural dynamics. Although significant differences in the relative centralization of care and reliance on community-based clinics are evident, the five cities discussed have incorporated an increased emphasis on preventive and primary care. The diversity among the systems is highlighted; adaptability is apparently a vital component in designing a public health care system appropriate to the needs of particular communities. Implications for Chicago and other cities are discussed. PMID- 1428972 TI - Training the urban health care provider: one department's first steps. AB - As our country faces a national crisis in health care, few have outlined plans to improve the shortage of primary care physicians. This is especially critical in urban areas where sociocultural impacts on health are large. The Department of Family Practice and Community Medicine at the University of Texas School of Medicine in Houston has begun development of a division of Urban Family Medicine to address the special training needs of the urban family practitioner. Subdivisions that have been formed focus on undergraduate curriculum, graduate educational strategies, service, and research and policy to further develop the training model. PMID- 1428973 TI - Urban health and the social contract: poverty, race, and death. PMID- 1428974 TI - Urban health care: an integral part of the United States health care system. PMID- 1428975 TI - Universal health care for Americans. PMID- 1428976 TI - PACE: a capitated model towards long-term care. PMID- 1428977 TI - Community health centers: a resource for service and training. AB - The American Medical Student Association (AMSA) Foundation is assisting the U.S. Public Health Service in increasing the number of primary care physicians trained and committed to practice in medically underserved areas. In collaboration with the American Academy of Family Physicians, the Ambulatory Pediatrics Association, and the Society of General Internal Medicine, AMSA conducted an assessment of federally-funded residency programs to identify and describe their affiliations with federally-funded community and migrant health centers (C/MHCs). Of the 260 programs assessed and the 147 responses, 125 offer community-based training. Of these, 73 offer training in primary care centers and 39 offer training in federally-funded C/MHCs. Residents training in the C/MHCs have positive experiences in both personal and professional development and are frequently hired by the health centers upon graduation. Benefits realized by the affiliations include a community orientation for the residents and enhancement of service and education missions for the collaborating institutions. PMID- 1428978 TI - Health care consortia: a mechanism for increasing access for the medically indigent. AB - In response to poor coordination among health and social service providers, health care consortia have emerged in many areas of the United States. Consortia link multiple providers in a common structure to create comprehensive systems of care. They can be formally structured or informal combinations of providers that engage in coordination but otherwise do not comprise an independent organization. The functions most common among all types of consortia are shared services and service coordination; however, a number of consortia also operate outreach/education programs. Consortia represent an innovative response to the need both for vertical integration--case management of all levels of care--and horizontal integration to prevent duplication among primary care providers. We outline the history of consortia in which federally-funded community health centers have participated. We also suggest an analytical framework for the various types of consortia; discuss lessons learned about building and maintaining consortia; and provide preliminary outcome data. PMID- 1428979 TI - The structure and function of urban pharmacies: visits to community pharmacies in inner-city Chicago. AB - Visits were made to 21 pharmacies in two poor neighborhoods on the west side of Chicago and interviews conducted with pharmacists-in-charge. The objective of the study was to provide a comprehensive description of the function, capabilities, and problems of urban pharmacy. We present results on the structure and function of these inner-city pharmacies. The pharmacies fit one of three structural forms: chain, independent, or medical center. The majority of respondents viewed the function of the inner-city pharmacy as patient-centered but also identified several barriers to effective patient communication. The results suggest that inner-city physicians and pharmacists should communicate with patients more often and in ways that patients understand. Also, Medicaid and other drug insurance programs should develop patient information networks and coverage packages intended to maximize patient health status. PMID- 1428980 TI - Urban health solutions in the 1990s: no time for false promises. PMID- 1428981 TI - Health priorities of the state of Michigan. PMID- 1428982 TI - Moving from health care research to action. AB - Although the United States spends more on health care than any country in the world, access to that care is becoming increasingly difficult. The National Cancer Institute and other federal agencies are sponsoring innovative research for delivering effective medical services, particularly to underserved populations. Models of successful collaboration between private and public sectors concerned with health care can be adapted and implemented at the national, state, and local levels. However, other measures are needed to ensure access to adequate health care for all Americans. Minimal but effective regulations are needed to ensure quality control, reduce duplication of services, and minimize cost increases. Public and private sectors also need to consider ways to extend adequate health insurance coverage to all Americans and to provide compensation for preventive services. PMID- 1428983 TI - Mount Sinai: a special hospital for a special community. PMID- 1428984 TI - The urban hospital: rediscovering abandoned values. PMID- 1428985 TI - Urban hospitals: their plight and mission. PMID- 1428986 TI - The epidemiology of prostate cancer in black men. AB - Data on the epidemiology of prostate cancer from the 1930s to the present document a dramatic racial difference in incidence, survival, and mortality rates in American men. American black men have the highest incidence and mortality rates of prostate cancer in the world. Survival data have been related to access to medical care, genetic and environmental factors, and cultural differences, including diet and social habits. Most reports present conflicting data with no clear positive correlations, and conclusions are often speculative. Better controlled, prospective studies of epidemiologic variables and a comprehensive genetic evaluation of black families with prostate cancer are needed to better understand the racial disparity affecting American black men and the biology of this disease in all men. PMID- 1428987 TI - Health Care Linkage Project: improving access to care. AB - The primary objective of the Health Care Linkage Project, funded by a grant from the Chicago Community Trust, is to develop, implement, and evaluate a primary health care linkage network within the city of Chicago that creates formalized linkages between community health centers, the Chicago Department of Health clinics, and hospitals. Six linkage networks are currently operational, with an additional two sites phased in during 1991. The success of the pilot project has been demonstrated by hundreds of patients receiving primary care and ancillary services on a more timely basis, by greater coordination between the public and private sector, by cost-savings to both patients and providers through reducing inappropriate use of services, and by a variety of spin-off projects which have improved the quality and accessibility of services. A second important objective is the development of a Health Care Linkage Manual that describes the practical experience and lessons gained from the linkages, the status of comparable arrangements in other U.S. cities, replicability of the linkage models, and recommendations for policy changes which will make linkages more effective. PMID- 1428988 TI - An update on the role of ploidy in prostate carcinoma. AB - One of the characteristic features of prostate carcinoma is its marked variation in biologic behavior. DNA quantitation has been studied in prostate carcinoma using a variety of techniques. Evaluation of tumor ploidy suggests that this may be the best predictor of the biologic behavior of prostate cancer in individual patients. This comprehensive review addresses the current studies, stage by stage, to clarify the clinical significance of these findings. PMID- 1428989 TI - Usage of penicillinase as an enzyme marker in enzyme linked immunosorbent assay for the detection of IgG antibodies to Toxoplasma gondii. AB - An Enzyme linked immunosorbent assay system has been developed using penicillinase as an enzyme marker for the detection of IgG antibodies to Toxoplasma gondii. This system is simple (end result assessed visually) reliable (the results are matching with other available commercial ELISA based kit), sensitive (detection of antitoxoplasma IgG antibodies to a level of 15 IU/ml) and reproducible (4.3 & 6.7% intra and inter coefficient of variation respectively). Experimental results with human serum samples using our system has shown consistent results and were in total agreement with other commercially available diagnostic kits. It is therefore suggested that ELISA system using penicillinase can be a simple, sensitive and reliable method for the diagnosis of toxoplasmosis in human. PMID- 1428990 TI - Comparison of penicillinase with horseradish peroxidase as enzyme tracer in ELISA for the toxin cleistanthin B. PMID- 1428991 TI - Detection of toxoplasma IgM antibodies by ELISA method: a comparative study of different enzymes as markers. AB - Detection of toxoplasma IgM antibodies by employing enzyme linked immunosorbent assay (ELISA) technique was developed using different enzymes viz, horseradish peroxidase (HRP) (EC. 1.11.17), urease (EC. 3.5.15) and penicillinase (EC 3.5.2.6) as markers. Of these enzymes, HRP is light sensitive and needs dark chamber, also inactivated by preservative sodium azide. Similarly urease test system is extremely pH sensitive and demands special care during ELISA technique. Whereas penicillinase showed certain distinct advantages viz. stable at room temperature, high specific activity and economical. In the present studies it was observed that the sensitivity of penicillinase is similar to HRP and urease, marker enzymes used in commercially available diagnostic kit. The prominent feature of detection of toxoplasma IgM antibodies involving these three enzymes are: a) Shorter incubation time (About 2.5 hours) b) No false positive reaction. Moreover, these enzyme conjugates were prepared from F (ab')2 fragments of antitoxoplasma rabbit serum to elicit specific interaction with IgM antibodies only, avoiding cross interaction with other non-specific proteins like compliment systems and rheumatoid factor. PMID- 1428992 TI - Pen-ELISA for immunodiagnosis and immunomonitoring of bancroftian filariasis. PMID- 1428993 TI - Indian scenario on the medical diagnostics business and future perspectives--an overview. PMID- 1428994 TI - Genesis of the development of the diagnostic test kits and their prospects: an overview. PMID- 1428995 TI - Dipstick ELISA kit for the detection of Cleistanthus collinus toxins. PMID- 1428997 TI - Localization of laminin in nephritic glomeruli as revealed by a quick-freezing and deep-etching method with immunohistochemistry. AB - The three-dimensional localization of laminin in rat glomeruli at the chronic phase of Masugi nephritis was investigated by a quick-freezing and deep-etching method combined with immunohistochemistry. Light-microscopically, laminin was localized in increased mesangial matrix and thickened glomerular basement membrane. The quick-freezing and deep-etching method revealed that the increased mesangial matrix, which was newly formed in axial portions and areas of mesangial interposition, was composed of fine fibrillar networks. They were revealed with the 3,3'-diaminobenzidine tetrahydrochloride (DAB) reaction products of peroxidase-labelled secondary antibody following anti-laminin antibody. However, these reaction products were not uniformly distributed in the newly formed matrix. Although the fibrils organizing lamina densa were also immunostained with anti-laminin antibody, the fibrils connected to mesangial cells, podocytes and endothelial cells had smaller amounts of DAB reaction products for laminin. These results indicate that one of the components of fibrils in the mesangial matrix and lamina densa is laminin, which is heterogeneously distributed in the newly formed matrix. PMID- 1428998 TI - Histochemical study of glycoconjugates in the nasal mucosa of the rat and guinea pig. AB - A histochemical study was carried out on the glycoconjugates of the nasal mucosa of rat and guinea pig using conventional techniques and peroxidase-labelled lectins. Both the respiratory mucosa and neuroepithelium were studied. Sulphate and sialic acid groups were found in the mucous layer of the neuroepithelia, Bowman's glands and goblet cells. In contrast, the nasal glands did not possess these groups, and only a few showed neutral mucins. Carbohydrate residues were more numerous in the acini of the Jacobson glands. Thus, the nasal glands in the rat and guinea pig are probably of a serous type because of the scarcity of carbohydrate residues. PMID- 1428999 TI - Electron microscopic immunocytochemical localization of proline-rich proteins in normal mouse parotid salivary glands. AB - Rabbit polyclonal antibodies against isoproterenol-induced mouse proline-rich proteins (PRPs) were used to localize PRPs in the parotid salivary glands of normal adult BALB/c mice. The antibodies recognized both acidic-type and basic type PRPs. Immunoblotting experiments revealed that the glands contained an acidic-type and a basic-type PRP. Parotid gland tissue was fixed with Karnosky's fixative and embedded in Lowicryl resin at low temperature. PRPs were localized at the electron microscope level using an indirect post-embedding staining technique with protein A-gold. The secretion granules of the acinar cells were strongly labelled. Pre-absorption of the antibody with purified acidic-type and basic-type PRPs indicated that the basic-type PRP is mainly located at the periphery of the granules but that the acidic-type PRP is more evenly distributed within the granules. Pre-absorption of the antibody with alpha-amylase did not affect the staining pattern, suggesting minimal cross-reactivity. PRPs were also detected within the rough endoplasmic reticulum and the Golgi apparatus of acinar cells, within the granules of the proacinar cells and in the lumena of the ducts, but not within the intercalated or striated duct cell granules. PMID- 1428996 TI - Dynamic nature and function of epidermal Langerhans cells in vivo and in vitro: a review, with emphasis on human Langerhans cells. AB - Epidermal Langerhans cells (LC) are Birbeck granule-containing bone-marrow derived cells, which are located mainly in the suprabasal layer of the epidermis. They can be readily identified by their strong expression of CD1a and MHC class II molecules. In addition to these 'classical' properties, an extensive phenotypic profile of normal human LC, summarized in this review, is now available. The powerful capacity of LC to activate T lymphocytes is clearly documented and, to date, LC are recognized as the prominent antigen-presenting cells of the skin immune system. They are generally believed to pick up antigens encountered in the epidermis and to migrate subsequently from the epidermis to the skin-draining lymph nodes. Upon arrival in the paracortex of lymph nodes, the antigen-laden LC transform into interdigitating cells and they present antigen to naive T lymphocytes in a MHC class II-restricted fashion; this results in the generation of antigen-specific immune responses. It has also been demonstrated that transformation of LC into interdigitating cells occurs when LC are cultured in vitro. Both in vivo and in vitro studies have indicated that properties of LC, such as phenotype, morphology and the stimulatory potential to activate T lymphocytes, are dependent on the local microenvironment in which the LC reside. The essential role of LC in the induction of contact allergic skin reactions and skin transplant rejection is well established. PMID- 1429001 TI - Prostaglandin E2 localization in the rat ileum. AB - The application of anti-prostaglandin E2 immunoglobulin to plastic-embedded thin sections of the rat ileum has permitted the localization of prostaglandin E2 in this tissue. In agreement with the published data (Chock & Schmauder-Chock (1988), Schmauder-Chock & Chock (1989)), the results also suggest the presence of an arachidonic acid cascade in the granules of various secretory cells of the gut. Since antibody labelling was found within the secretory granules of connective tissue mast cells, goblet cells, and Paneth cells, the presence of the arachidonic acid cascade in these granules is implied. The appearance of prostaglandin E2 over the non-cellular internal elastic lamina of arterioles suggests that it may have been secreted along with the elastin. The even distribution of prostaglandin throughout the cytoplasm of the erythrocyte is consistent with the concept that this cell scavenges the eicosanoid from the circulation. These data further link the secretory granule to the production of eicosanoids and therefore illustrate the potential sources of prostaglandins in the rat ileum. PMID- 1429000 TI - Immunoelectron microscopic studies of glycosaminoglycans in the metaphyseal bone trabeculae of growing rats. AB - The types and distribution of glycosaminoglycans (GAGs) were studied immunocytochemically in osteoid, mineralized bone matrix, and cartilage matrix of growing rat metaphyseal bone after aldehyde fixation and EDTA demineralization, using four monoclonal antibodies (mAbs 1-B-5, 2-B-6, 3-B-3 and 5-D-4). These mAbs specifically recognize epitopes in non-sulphated chondroitin (C0-S); chondroitin 4-sulphate (C4-S) and dermatan sulphate (DS); chondroitin 6-sulphate (C6-S) and C0-S; and keratan sulphate (KS) respectively. In osteoid, all mAbs except 1-B-5 weakly stained matrix material on and between collagen fibrils, and moderately stained organic material corresponding to bone nodules, which are known sites of mineralization. However, the staining of osteoid abruptly decreased at the mineralization front; weak staining was confined mostly to the organic material of bone nodules in mineralized bone matrix, with very weak or no staining of the rest of the bone matrix. This staining progressively decreased toward the mineralized cartilage matrix and became negative. The mineralized cartilage matrix and lamina limitans reacted strongly with all mAbs except 5-D-4. These results indicate that osteoid contains sulphated proteoglycans containing C4-S and/or DS, C6-S and KS, and subsequent bone matrix mineralization appears to require accumulation of these macromolecules within bone nodules and eventual loss of these substances for complete mineralization, whereas proteoglycans containing C0-S, C4-S and/or DS, and C6-S still exist in mineralized cartilage matrix and lamina limitans. PMID- 1429002 TI - Calbindin D-28k-immunoreactivity in rat muscle spindles during postnatal maturation and after denervation. AB - Calbindin D-28k-immunoreactivity has been demonstrated in some of the intrafusal muscle fibres and in the capsule of adult rat muscle spindles. In this study, the immunocytochemical localization of calbindin D-28k in the muscle spindles of triceps surae muscle was studied during postnatal maturation and after denervation. In young rats calbindin D-28k-immunoreactivity was seen in a few intrafusal fibres, first at the age of 4 days. At the 7th day, three calbindin D 28k-immunoreactive fibres and one unlabelled fibre were seen in most muscle spindles, as in adult rats. The spindle capsule and perineurial sheath of nerves were first seen to exhibit calbindin D-28k immunoreactivity at the age of 14 days, and thereafter the localization of calbinding D-28k-like immunoreactivity was similar to that in adult rats. After denervation, calbindin D-28k immunoreactivity remained in intrafusal muscle fibres and the spindle capsule for a long period. After two months of denervation, calbindin D-28k immunoreactivity could still be seen in the spindle capsule, but the intrafusal fibres were not labelled. The innervation is known to have trophic effects on the intrafusal fibres. The present findings suggest that the expression of calbindin D-28k immunoreactivity in maturating muscle spindles may be induced by the developing innervation. The decrease of calbindin D-28k-immunoreactivity in intrafusal fibres after denervation may be due to the loss of trophic factors released by the nerves. PMID- 1429004 TI - Cellular heterogeneity in human transitional cell carcinoma: an analysis of optical properties and lectin binding. AB - Flow cytometry was used to measure the binding of a panel of ten fluorescein isothiocyanate(FITC)-conjugated lectins to fifteen samples of normal and neoplastic human urothelium. Concurrent measurement of light scattering and fluorescence permitted the quantification of lectin binding to cellular subpopulations defined by their light-scattering properties. In normal urothelium, we previously demonstrated levels of lectin binding to the cellular subpopulations derived from the superficial and intermediate cell layers which were higher than levels which bound to the subpopulation derived from the basal cell layer (Ward et al., 1987). This difference was most marked with Maclura pomifera agglutinin (MPA), Ricinus communis agglutinin (RCA) and Ulex europeus agglutinin (UEA). We now report a similar correlation between the degree of differentiation of a cellular subpopulation and the level of lectin binding in human transitional cell carcinomas (TCCs). Morphological differentiation in human TCCs is accompanied by alterations in cell-surface carbohydrates which are similar to those which accompany cellular differentiation in the corresponding normal tissue. No systematic difference in lectin binding was observed between the corresponding subpopulations of normal and neoplastic urothelial cells. PMID- 1429003 TI - A chromogranin peptide is co-stored with insulin in the human pancreatic islet B cell granules. AB - The immunoreaction of a rabbit chromogranin A and B antiserum was studied in normal human pancreatic islets. By examination of consecutive light microscopical sections, it was revealed that, at high antiserum concentrations (1:2000 or less), the whole islet area was heavily labelled, although the peripheral glucagon (A)-cells were the most intense in their immunoreaction. At low antiserum concentrations (1:4000 or more) the A-cells still showed the same intense labelling reaction, but the central B-cells were weakly labelled. Electron microscopically, reactivity towards the chromogranin A and B antiserum and the monoclonal insulin antibodies was present in the same central electron dense core of the B-cell secretory granules, as demonstrated after application of the immunogold technique at different antibody dilutions. In the A-cells, the chromogranin immunoreactivity was concentrated at the peripheral mantle of the secretory granules. The D-cell granules showed a weak immunolabelling. Examination of human islets with the monoclonal chromogranin A antibody LK2H10 revealed immunogold labelling only in the peripheral mantle of the A-cell granules, while the B-cell granules were unlabelled. The present results show that a chromogranin peptide is co-stored with insulin the in normal human B-cell secretory granules. Although the exact composition of this B-cell chromogranin is unknown, it is not identical to that of the chromogranin A present in the A-cell granules. PMID- 1429005 TI - Characterization of a human cervical carcinoma-associated antigen by lectin binding and immuno-electron microscopy. AB - The specific binding and nature of the epitope recognized by monoclonal antibody (Mab) 1H10, which binds an antigen expressed on human cervical tumors, was characterized by enzyme digestion, lectin competition assay and immuno-electron microscopy. Membrane homogenates of CaSki cervical carcinoma cells were digested with various enzymes, then analysed by SDS-PAGE and immunoblotting. Cells grown on coverslips were treated with various enzymes and in situ binding of Mab 1H10 to cells was analysed by electron microscopy. The ability of lectin-conjugates to block Mab 1H10 binding to CaSki cells was also examined. Treatment of samples with sodium periodate abrogated antigen recognition by Mab 1H10. Neuraminidase and hyaluronidase digestion decreased but did not eliminate Mab 1H10 binding to cells in situ. Chondroitinase ABC digestion, in contrast, removed Mab 1H10 binding sites both in vitro and in situ. Trypsin and chymotrypsin digestion of cell membrane homogenates decreased the molecular weight of the Mab 1H10 antigen but did not decrease the binding intensity. Wheat germ agglutinin (WGA) strongly bound to CaSki cells and partially blocked Mab 1H10 binding, indicating that the antigen contains N-acetyl-galactosamine residues at or near the epitope recognized by Mab 1H10. Ricinus communis agglutinin (RCA) exhibited a similar binding pattern to WGA. However, concanavalin A bound only weakly to CaSki cells and was ineffective at blocking Mab 1H10 binding. The tumor-associated antigen recognized by Mab 1H10 is concluded to be a chondroitin sulphate glycoprotein or proteoglycan rather than a mucopolysaccharide or lipoprotein. PMID- 1429006 TI - Immunohistochemical, autoradiographic and electron microscopic studies on the transformation of fibroblasts into chondrocytes in the mouse subfascia induced by bone morphogenetic protein. AB - Functional morphology on the transformation of fibroblasts into chondrocytes induced by bone morphogenetic protein (BMP) was studied by light and electron microscopy using 35S autoradiography and immunohistochemistry for S-100 protein and type-II collagen. A pellet containing BMP obtained from a murine osteosarcoma was transplanted into the mouse subfascia. By 3 days after implantation, many typical fibroblasts, which were free of the silver grains for 35S and devoid of both S-100 protein and type-II collagen, entered the pellet region. By 5 days, the fibroblasts in the pellet region became polygonal in shape, and cytoplasmic vesicles and vacuoles appeared, both containing a homogeneous substance of low electron density. At 5 days, autoradiography revealed many silver grains for 35S over the Golgi apparatus and vesicles and vacuoles of the cells in the pellet region as well as over the surrounding extracellular matrix. Moreover, the cells at 5 days displayed immunoreactivity to both proteins. The extracellular matrix around the cell began to show clear metachromasia and increased in amount with time. At 9 days all the cells in the pellet region were round or oval in shape and surrounded by an abundant cartilaginous matrix. The rough endoplasmic reticulum and Golgi apparatus were extremely well developed, and a large number of vacuoles and vesicles were seen in the cytoplasm. These cells showed intense immunoreactivity to both proteins, and strong accumulation of sulfur was visualized in the extracellular matrix by autoradiography. These results suggest that the fibroblasts in the pellet region change into chondroblasts by 5 days, and become typical chondrocytes by 9 days. PMID- 1429007 TI - Lectin-binding carbohydrates in sexual differentiation of rat male and female gonads. AB - Development and sexual differentiation of the mammalian gonad involve changes in the type and distribution of different proteins and glycoproteins in and around the epithelial gonadal cords, the future seminiferous tubules in the testis, and follicles in the ovary. To study changes in cellular carbohydrate-containing compounds in the sex-specific morphogenesis of rat gonads, sections from embryonic, fetal and early postnatal gonads were labelled with seven different fluorescein isothiocyanate (FITC)-conjugated plant lectins of various carbohydrate-binding specificities. Double labelling of laminin with tetramethylrhodamine isothiocyanate (TRITC)-conjugated antibodies was used to outline the epithelial tissues. From the results we conclude that the abundance and similar distribution of carbohydrates in the early gonads of both sexes supports their sexually indifferent nature. Furthermore, the basement membranes of the differentiating gonadal cords in both sexes have common features, which differ, however, from those of the other developing urogenital organs. Changes in carbohydrate composition appear with the sexual differentiation of the gonads; the similarity of the changes in lectin binding to the gonadal cords of embryonic and fetal male, and to postnatal female, suggests similar mechanisms of cell-cell interactions in both sexes although activated at different developmental stages. These carbohydrate specificities at the tissue level should be taken into account together with cell-type specific changes, e.g. in the formation of the zona pellucida, when the phenomenon of polymorphic expression of different compounds is integrated into theories of epithelial differentiation. PMID- 1429009 TI - Electron microscopic characterization of calcium-binding physodes in the green alga Mougeotia scalaris. AB - Effect of the covalently cross-linking agents glutardialdehyde and osmium tetroxide, and of adsorption of the vital dye, neutral red, to the matrix of the calcium-binding "vesicles" from the green alga Mougeotia scalaris has been analysed in situ, both in terms of structural preservation and of the calcium binding capacity of the vesicles. Upon cell fixation in glutardialdehyde without OsO4, the vesicles appear to dissolve, but upon simultaneous fixation in glutardialdehyde with OsO4 (1% w/v), the vesicles retain a globular form, are evenly stained by osmium and appear to be surrounded by a membrane-like structure. This structure was also observed around the vesicles in cells preincubated for 10 min in 0.1 mM neutral red and then fixed in glutardialdehyde/OsO4 for 1 h. More detailed information of the matrix structure is obtained when simultaneous fixation of the Mougeotia cells was shortened to 15 min: a membrane-like structure was no longer observed around the vesicles. After cell treatment in the presence of neutral red, no calcium at all was found inside the vesicles. A small amount of calcium remained, when cells were fixed simultaneously and extensively in the absence of neutral red. However, calcium was found, to a considerable extent, inside the vesicles after short simultaneous fixation of the cells in the absence of neutral red. Based on the ultrastructural and elemental features presented here, the calcium-binding vesicles in Mougeotia appear to represent a member of the large family of (calcium-binding) physodes in lower plants (CaBP). PMID- 1429008 TI - Neural regulation of differentiation of rat skeletal muscle cell types. AB - Three monoclonal antibodies (LM5, F2 and F39) to the fast class of myosin heavy chain (MHC) were used to study the effect of denervation on the differentiation of muscle cell types in some rat skeletal muscles. Antibody LM5 in immunocytochemical investigations did not stain any myotubes during early fetal development but presumptive fast muscle cells started to stain during later fetal development. Unlike antibody LM5, antibodies F2 and F39 stained all myotubes during fetal development. The suppression of fast myosin heavy chains recognised in presumptive slow muscle cells was observed within 1-2 days after birth with antibody F39 but not until 10-14 days after birth with antibody F2. The emergence of subsets of fast muscle fibre types in rat extensor digitorum longus (EDL) and tibialis anteri (TA) detectable by F39 and F2 antibodies was not observed until 2 3 weeks after birth. Denervation of developing muscles led to marked changes in the expression of myosins identified by these antibodies. PMID- 1429010 TI - Induction of G- and R-banding in human chromosomes by the demethylating agent S adenosyl-L-homocysteine. AB - In this report we describe the procedure of growing human lymphocytes with the demethylating agent S-adenosyl-L-homocysteine (SAH). After this treatment, which is not toxic for cell survival, both R- and G-banding were obtained by new experimental procedures: R-bands have been directly demonstrated with the GC specific fluorochrome chromomycin A3 without the necessity of any AT-specific counterstaining agent; simultaneous G-banding and active nucleolar organizer regions have been obtained by silver impregnation of chromosomes and subsequent Giemsa staining. These results suggest a possible relationship between local differences in DNA methylation and the determination of the banded chromosome structure. PMID- 1429011 TI - Molecular characterization of "inverted" pericentromeric heterochromatin of chromosome 3. AB - Inversion of the pericentromeric region of human chromosome 3 [inv (3) (p11q11.2)] is a rare event. Initially, this inversion was identified with staining for Q-bands by fluorescence using quinacrine (QFQ) and later characterized with staining for C-bands by CBG technique. The molecular methods of fluorescence in situ hybridization (FISH) and AluI/Giemsa and TaqI/Giemsa techniques were utilized. The findings suggest that the variable band q11.2 on chromosome 3 contains alphoid DNA sequences, which appear to be similar to those identified by conventional methods in the centromeric region (band p11). PMID- 1429012 TI - Ecdysteroid binding sites in gastrolith forming tissue and stomach during the molting cycle of crayfish Procambarus clarkii. AB - The distribution of ecdysteroid binding sites in the stomach and gastrolith disc tissue of crayfish (Procambarus clarkii) was examined in relation to the molting stage by thaw-mount autoradiography. The radiolabeled hormone analogue ponasterone A (25-deoxy-20-hydroxyecdysone) was used. Ecdysteroid binding sites were demonstrated only in certain molting stages, the small gastrolith period and the aftermolt stage. In gastrolith epithelium, ponasterone A binding sites first appeared in the cytoplasm, and then in the nuclei and cytoplasm. In the stomach epithelium, many nuclear binding sites were detectable during the period of gastrolith secretion. These periodical changes in specific ponasterone A binding when correlated with the molting stages clearly show that ecdysteroids may function as an initiator for gastrolith formation and reabsorption. The findings also suggest that ecdysteroids control calcium transport in the stomach epithelium. The time-related and functional differences of cytoplasmic and nuclear concentration of ecdysteroid receptors indicate the presence of cytoplasmic and nuclear receptors associated with specific actions. PMID- 1429013 TI - Direct detection of immunogold reactions by real-time video microscopy. AB - Video-enhanced microscopy allows the detection and tracking of individual colloidal gold particles. The analysis of immunogold reactions can also be conducted as a function of time and thus allows the study of dynamic events in living cells. The direct visualization in real time is reported of the reaction of immunogold particles with a surface antigen. This time-resolved immunocytochemistry was achieved by continuous observation of living cells infected with a virus (respiratory syncytial virus) following their incubation with colloidal gold (30 nm) coated with antiviral antibodies. The progress of the immunoreaction was visualized as a sequential deposition of individual gold granules on the viral particles until saturation was reached after 60 min. Binding of colloidal gold was an irreversible event as no elution or dislocation of surface-bound granules took place. Comparative imaging of colloidal gold particles by electron microscopy and by video microscopy demonstrated that the video-imaged immunoreactions represented events involving single gold particles; their signal was sometimes clearly enhanced by secondary depositions taking place in close proximity, i.e. at a distance below the lateral resolution of the light microscope. Our experiments demonstrate that video-enhanced microscopy provides a powerful tool for studying antibody-antigen reactions with a high spatial and temporal resolution. PMID- 1429015 TI - FMRFamide-immunoreactive structures in the brain of the brown hagfish, Paramyxine atami: relationship with neuropeptide Y-immunoreactive structures. AB - Localization of the molluscan cardioexcitatory tetrapeptide FMRFamide (Phe-Met Arg-Phe-NH2) in the brain and hypophysis of the brown hagfish, Paramyxine atami, was examined by immunohistochemistry specially regarding a possible relationship with neuropeptide Y (NPY). FMRFamide-immunoreactive fibers were demonstrated in many regions of the brain, with the highest density in the diencephalon. However, no immunoreactivity was found in the hypophysis. Labeled cells were chiefly located in the nucleus hypothalamicus of the diencephalon, although a few cells were recognized in the ventrolateral area of the caudal tegmentum. Examination of adjacent sections immunostained alternatively with anti-NPY antiserum and anti FMRFamide antiserum showed overlapping of the distributional patterns of the immunoreactive structures in the brain. Moreover, the same cells in the nucleus hypothalamicus were immunostained with both antisera. Cross-blocking experiments showed that the FMRF-amide-immunoreactivity is abolished by preabsorption of the antiserum with homologous antigen, but not eliminated completely by pretreatment with appropriate antigens (NPY, avian pancreatic polypeptide and methionine enkephalin-Arg-Phe). In contrast, the NPY-immunoreactivity was blocked by pretreatment of the antiserum with NPY, pancreatic polypeptide or FMRFamide, although no blocking by enkephalin was observed. Accordingly, the present study shows that, in the brown hagfish, FMRFamide-immunoreactive structures in the brain can be recognized by anti-NPY antiserum. PMID- 1429014 TI - Nuclear matrix-bound replicational sites detected in situ by 5-bromodeoxyuridine. AB - The nuclear matrix was prepared in situ from Swiss 3T3 cells, which were synchronized by contact inhibition and serum starvation and pulse-labelled for very short periods of time with 5-bromodeoxyuridine (5-BrdU). For the first time 5-BrdU has been employed to demonstrate the association of newly synthesized DNA with a nucleoskeleton. Immunofluorescence analysis using a monoclonal antibody to 5-BrdU revealed five different intranuclear staining patterns at different stages of the S phase. These patterns were observed also in intact cells and did not change during the matrix preparation steps which involve extraction with 2 M NaCl and DNase I digestion. Such an observation was also confirmed by spatial confocal microscopy studies. The intensity of fluorescence, which was evaluated by cytofluorometry, increased to reach a maximum during mid-S phase and then decreased. Because no significant difference was found in the time to label residual DNA of different 5-BrdU staining patterns, this strongly suggests that a different number of replicons is activated at different stages of the S phase. These results strengthen the hypothesis that eukaryotic DNA replication occurs in close association with an insoluble protein nuclear skeleton, which determines the three-dimensional spatial organization of chromosome duplication. PMID- 1429016 TI - Sensitive mRNA detection using unfixed tissue: combined radioactive and non radioactive in situ hybridization histochemistry. AB - In the present study some experimental parameters for in situ hybridization histochemistry (ISHH) have been analysed using 35S-labelled and alkaline phosphatase-conjugated probes, in order to develop a reproducible double labelling procedure. We have compared the total exclusion of tissue fixation with tissue sections fixed by immersion in formalin. In addition, the effect of dithiothreitol was assessed both when combining radiolabelled and non-radioactive probes on a single tissue section and when the probes were used separately. Hybridization of unfixed tissue resulted in stronger specific labelling and lower background both for radiolabelled and alkaline phosphatase-conjugated probes. No loss in tissue preservation was seen at the light microscopic level after hybridization of unfixed tissue. High concentrations (200 mM) of dithiothreitol strongly suppressed background when using 35S-labelled probes, whereas in the non radioactive procedure, alkaline phosphatase labelling could only be achieved with very low dithiothreitol concentrations (less than 1 mM). This incompatibility led to a protocol using unfixed tissue sections and a sequential hybridization procedure, with the radiolabelled probe and high concentrations of dithiothreitol in the first step and the alkaline phosphatase-conjugated probe without dithiothreitol in the second step. PMID- 1429017 TI - Initial reaction kinetics of succinate dehydrogenase in mouse liver studied with a real-time image analyser system. AB - The initial reaction kinetics of succinate dehydrogenase in situ were investigated in sections of mouse unfixed liver using an ARGUS-100 image analyser system. The sections were incubated on substrate-containing agarose gel films. Images of a section, illuminated with monochromatic light (584 nm), were captured with the image analyser in real time at intervals of 10 s during the incubation. The absorbances of selected hepatocytes in the successive images were determined as a function of time. In every cell, the absorbance increased nonlinearly after the first minute of incubation. The initial velocity of the dehydrogenase was calculated from the linear activities during the first 20 s of incubation. Hanes plots of the initial velocities and succinate concentration yielded the following mean kinetic constants. For periportal hepatocytes, the apparent Km = 1.2 +/- 0.8 mM and Vmax = 29 +/- 2 mumol hydrogen equivalents formed/cm3 hepatocyte cytoplasm per min. For pericentral hepatocytes, Km = 1.4 +/- 1.0 mM and Vmax = 21 +/- 2 mumol hydrogen equivalents/cm3 per min. The Km values are very similar to those determined previously from biochemical assays. These results, and the observed dependence of the initial velocity on the enzyme concentration, suggest that the technique reported here is valid for the histochemical assay of succinate dehydrogenase. PMID- 1429018 TI - Distribution of hyaluronan and its CD44 receptor in the epithelia of human skin appendages. AB - Biotinylated hyaluronan (HA) binding complex (HABC) from bovine articular cartilage proteoglycan was used as a histological probe to study the localization of HA in human skin. The distribution of HA was compared with its presumptive cell surface receptor, CD44, using monoclonal antibodies. In epidermis both HA and CD44 were found in the basal and spinous cell layers, but neither was present in the stratum granulosum and stratum corneum. In the keratinizing parts of hair follicles, i.e. in the outer and inner epidermal root sheath, pilosebaceous duct and the actual hair, HA and CD44 were found between the vital but not the terminally differentiated cells. In the sebaceous glands a small amount of HA was found around all cells, whereas CD44 was restricted to the basal cell layer. The secretory acini of the sweat glands stained intensively with anti-CD44 antibodies but only weakly with HABC. In the sweat gland, CD44 was localized on the basal and lateral surfaces of the clear cells, whereas the dark cells and the myoepithelial cells were negative. Both the lower and upper layers of the sweat gland ducts showed a faint but constant staining for CD44 and only minor amounts of HA. While in the keratinizing skin epithelia both HA and its CD44 receptor showed an intense staining with a close co-distribution, in the sweat and sebaceous glands their distribution patterns were not similar. It is suggested that in epithelia with divergent differentiation programs the functions of CD44 and HA may be different. PMID- 1429019 TI - Immunohistochemical localization of pancreatic spasmolytic polypeptide (PSP) in the pig. AB - Pancreatic spasmolytic polypeptide (PSP) is a peptide that is isolated from the porcine pancreas and that affects intestinal motility and growth of intestinal tumour cells in vitro. The peptide was recently demonstrated to be present in large amounts in pancreatic juice. The cellular origin of the peptide, however, is largely unclarified and the localization was therefore studied of PSP in pigs using immunohistochemistry. Positive immunoreactions were seen in the pancreas, the stomach, the duodenum, the jejunum and the ileum. In the pancreas, the PSP immunoreaction was seen in all acinar cells; no immunoreaction was seen in the endocrine islets. In the stomach, it was localized to the mucous cells of the glands in the cardiac gland region, the corpus and the pylorus. In the duodenum a strong immunoreaction was present in Brunner's glands and in the cells of their excretory ducts. In the jejunum and ileum, PSP immunoreactivity was seen in some of the cells in the epithelium of the crypts of Lieberkuhn. A peptide chromatographically identical to highly purified PSP was identified in pancreas and stomach extracts. Thus epithelial cells in all parts of the stomach and small intestine contribute to the supply of PSP to the gut lumen. PMID- 1429020 TI - 5'-nucleotidase in spinal meningeal compartments in the rat. An immuno and enzyme histochemical study. AB - The distribution of 5'-nucleotidase (5'-Nu) is reported in spinal meninges of the rat on the basis of an immunohistochemical and enzyme histochemical investigation. Strong immunoreactivity was found in the arachnoid membrane and in the sheaths of the spinal roots as well as in septa subdividing the roots. Also the superficial layer of the ligamentum denticulatum showed enzyme staining. No immunoreactivity could be detected in the pia mater or along the spinal nerve roots outside the subarachnoid space. Within the arachnoid mater the immunoreactivity was concentrated in the basal zone of the arachnoid membrane, thus appearing as a narrow fluorescent band near the border of the dura. An accentuation of immunoreactivity could be observed in areas where small dural blood vessels approach the subarachnoid space. It is well known that adenine nucleotides released from neural and glial cells of the central nervous system finally reach the cerebrospinal fluid. We presume that 5'-Nu in the arachnoid membrane and spinal root sheaths is responsible for the conversion of adenine nucleotides into adenosine and that this conversion is associated with the reabsorption process of cerebrospinal fluid which most probably also takes place in spinal meninges. Adenosine, the product of 5'-nucleotidase, could play a role in the reabsorption process by its vasodilatatory effect on dural and epidural vessels. PMID- 1429021 TI - Amalgamation of two endocytic probe techniques: fluoresceinated cationized ferritin can show up, sequentially, selected structures, first in living cells and then by electron microscopy. AB - Fluorescein isothiocyanate-cationized ferritin (FITC-CF) has hitherto been used mainly to identify structures in living cells by light microscopy, by virtue of its fluorescent properties. We show here that this conjugate can be used, after immediate fixation of the same cell sample and preparation of thin sections, to recognise the same structures, by virtue of the ferritin's electron opacity. The conjugate should thus have a new use as a single-application, dual-purpose probe, e.g. in endocytic studies. The procedure may have advantages over similar dual purpose probes in not requiring staining or special treatment. PMID- 1429022 TI - Fibronectin and laminin in transverse tubules of cardiac myocytes studied by laser confocal microscopy and immunocytochemistry. AB - The distribution of two non-collagenous glycoproteins of high molecular weight, fibronectin (FN) and laminin (LMN), was investigated in myocardial cells from the ventricle of rats, and from biopsies collected from the auricle of patients undergoing a coronary bypass operation. In order to elucidate the expression of FN and LMN across cells, non-invasive serial sectioning has been carried out by laser scanning confocal microscopy of frozen, immunostained tissue sections. In addition, immunoelectron microscopy was used to study the distribution of these antigens at higher magnifications. These studies show that FN is part of the basement membrane of the surface sarcolemma of both ventricular and atrial cells, in addition to being an abundant protein of the extracellular matrix (ECM). Along transverse tubular(TT)-membranes, FN was only detected in tubules exceeding 200 nm in diameter. Even here, the intensity of labelling varied greatly and was generally low. By contrast, a heavy investment of LMN was organized in the basal lamina along the surface sarcolemma and along ramifications of the entire TT system in ventricular heart muscle cells. In this way, the network of TT-membrane systems of working heart muscle cells provides a supply of LMN to all depths of the myocardial fibre. In human atrial muscle cells, a regular TT-system appears to be absent. Instead occasional, deep sarcolemmal invaginations occur with diameters of 300-500 nm, the surfaces of which are also invested with LMN. The significance of the present findings has been discussed, with special reference to LMN as a possible component of a series of proteins involved in transmembrane communication between the ECM and the sarcoplasm. PMID- 1429023 TI - Which fluorophore is brightest? A comparison of the staining obtained using fluorescein, tetramethylrhodamine, lissamine rhodamine, Texas red, and cyanine 3.18. AB - There are several red-emitting fluorophores available for immunofluorescence studies, including tetramethylrhodamine, lissamine rhodamine, Texas Red, and cyanine 3.18; however, it is unclear which of these is best. The present study compared the brightness of these fluorophores to that of fluorescein. Staining was attempted using a primary antibody raised against serotonin and a secondary antibody that was conjugated with either fluorescein or one of the red fluorophores. The intensity of staining was determined densitometrically. It was found that a conjugate of cyanine 3.18 provided significantly brighter staining that conjugates of any of the other fluorophores, including fluorescein. It is concluded that cyanine 3.18 should be useful for multicolor fluorescence experiments and that it may be the brightest fluorophore available for single color fluorescence immunocytochemistry. PMID- 1429024 TI - [Expert assessment of hearing loss within the scope of the social compensation law and the law regarding severely handicapped patients]. AB - Special problems are described concerning expert opinions on hearing disability and hearing loss with regard to the German Social Rights for Compensation and the laws for handicapped persons. In some aspects there are similarities to the rights of accident insurance, but disability programs question only the degree of handicap present and not the source of the hearing loss. The expert opinion on the subject's ability to work in his or any other profession must only determine the patient's ability to hear and the tasks needed to fulfill the profession. Special attention is given to the problems arising from tinnitus. PMID- 1429025 TI - [The cochlear implant in childhood. Possibilities, limits and perspectives of management]. AB - Therapeutic experiences with cochlear implants in late adult deafness have become so large that implants now belong to the accepted methods of therapy for profoundly deaf patients. Affected patients often recognize speech through simple auditory means. In the last 5 years increased numbers of children with congenital or infantile deafness have also been successfully treated with cochlear implants. Some reports have already been published about clinical experiences and rates of success. In this paper some positive results are shown, but the limitations of treatment and the necessity for accurate preoperative diagnosis must be understood. The further development of treatment for deaf implants requires refinements in phoniatric and pedaudiological techniques. PMID- 1429026 TI - [Experimental defects of the round window membrane]. AB - Previous and current studies of experimentally induced fistulas in the round window membrane (RWM) are reviewed. After puncture (or "micro-perforation") of the RWM leaking perilymph was not been observed and auditory evoked potentials have remained unaltered. In contrast, most publications have reported that gross incisions ("macro-perforations") of the RWM have resulted in the deterioration of auditory evoked potentials, with leaking perilymph and/or cerebrospinal fluid and/or with entrance of air bubbles into the scala tympani depending on the site of the perforation. Spontaneous healing was then observed within 4 to 8 days and was associated with normalization of the auditory evoked potentials. In a very few experimental studies pathophysiological mechanisms were simulated that may be involved clinically in patients with RWM fistulas, i.e. implosive rupture of the RWM due to an acute increase in middle ear pressure or explosive rupture of the RWM that may occur in patients trying to use forced Valsalva maneuvers to equalize decreased middle ear pressures due to blocked Eustachian tubes. PMID- 1429027 TI - [Neurovascular contacts in the inner ear canal and cerebellopontile angle. A methodologic comparison between CT with pneumocisternomeatography and MR angiography]. AB - The interaction between arterial loops and the vestibulocochlear nerve is considered to be responsible for such clinical symptoms as progressive sensorineural hearing loss, tinnitus and vestibular dysfunction. Previously, neurovascular relationships were best demonstrated with invasive Gas-CT cisternography, although this technique resulted in a low detection rate of 38%. Magnetic resonance angiography offers a non-invasive method for imaging vessel loops in the cerebellopontine angle without contrast medium in more than 90% of cases. A comparison between gas-CT-cisternography and magnetic resonance angiography in 9 patients revealed a superior simultaneous depiction of both anterior inferior cerebellar arteries with magnetic resonance angiography. PMID- 1429028 TI - [Psychogenic hearing disorders in childhood and adolescence]. AB - Psychogenic hearing defects are more common than previously recognized. The disorder is characterized by typical behaviour, audiological signs and symptoms. Patients may show severe hearing losses as evaluated by pure-tone threshold audiometry but can understand usual conversation. Results of audiological examination may be conflicting and suggest a wide range of organic hearing disorders. Other characteristics are dramatic improvement of hearing following sham procedures or placebo medication. Detection of psychogenesis and etiologic factors are of utmost importance for successful therapy. Between 1988 and 1991, 21 children and adolescents (ages 5-16 years) with psychogenic hearing losses were studied. Typical signs as well as diagnostic and therapeutic tools are illustrated in renewal case histories. In-patient diagnosis and treatment are recommended, since improvement was achieved in all patients treated. PMID- 1429029 TI - [Systematic hearing diagnosis in the premature infant. The Magdeburg model]. AB - Almost 50% of all hearing disorders found in children are acquired. To a large extent these hearing disorders are caused by premature birth and can be detected by suitable screening. Two methods have proved useful for such testing: (1) Reflex audiometry with a standardized stimulus generator; and (2) bedside recording of brainstem potentials. Having tested the method of bedside recording of brainstem potentials we examined a group of 60 infants of varied body weights and otherwise normal findings as a "normal" control group. At all click intensities measured, premature infants weighing from 1500 to 2000 g showed a latency increase by about 0.7 ms when compared to infants weighing in excess of 2000 g. Premature infants showing signs of maturation adequate for gestational age were not at greater risk for hearing disorders. In contrast, premature infants weighing less than 1500 g and having marked hyperbilirubinemia as week as extensive intracranial bleeding always showed increased wave V latencies. Ten percent of these infants had severe hearing disorders requiring special pecaudiological training. Overall findings showed the great usefulness of audiometric screening in a pediatric hospital center for detecting hearing disorders in premature infants. PMID- 1429030 TI - [The definition of "selectivity" in reduced speech discrimination as a sequela of peripheral perceptual damage]. AB - The term "selectivity" means the ability to correctly select speech in the presence of other kinds of noise. In the literature the term "selectivity" is used very differently with regard to the different levels of the hearing system. In actual practice a separation of this term is important for possible audiometric topodiagnosis study. The problems of selectivity in hearing are discussed and different terms are proposed regarding the different planes of hearing system: 1. for the interaural-external ear transfer function, the terms "stereophonic outer ear effect" or "stereophonic outer ear efficiency" are used; 2. for the power of the inner ear, the term "ability of analysis"; 3. for the central auditory pathways, the term "chiasmatic selectivity" or "meshing selectivity"; 4. for the cortical centre, "active selectivity." The audiometric test batteries used clinically for topodiagnosis are discussed and two examples shown to illustrate the usefulness of the distorted Freiburg Word Test for detecting "analytical ability" in cases of inner ear damage. PMID- 1429031 TI - [Carcinoid of the middle ear: a rare tumor with biphasic differentiation. Case report with special reference to immunohistochemistry and electron microscopy]. AB - Progressive unilateral sensorineural deafness and tinnitus developed in a 59-year old woman over a 1-year period. Clinical examination showed a tumor mass which almost completely filled the tympanic cavity, and grew around the auditory ossicular chain. Histological findings revealed the tumor to be a primary carcinoid of the middle ear. Neuro-endocrine differentiation was confirmed immunohistochemically by positivity for neuron-specific enolase, chromogranin, pancreatic polypeptide and synaptophysin. Using electron microscopy, neuroendocrine granules could be visualized. In addition, both light and electron microscopy revealed that cells had an epithelial differentiation with mucin granules while immunohistochemistry showed a positivity for cytokeratins. The detection of intermediary filaments (immunohistochemically with vimentin and under electron microscopy) was unique to this neoplasm and has to be considered in distinguishing the carcinoid tumor from the papillary adenoma of the middle ear. Tumor prognosis is excellent with radical extirpation from the middle ear. In the case presented, there has been no evidence for either recurrence or metastases 10 months after surgical resection. PMID- 1429032 TI - HLA class-II-mediated homotypic aggregation: involvement of a protein tyrosine kinase and protein kinase C. AB - Homotypic aggregation of B-lymphocytes, B-cell lines and class-II-positive T cells via HLA class II molecules was examined. Signaling via DR antigens induced rapid aggregation in a dose- and time-dependent manner, maximum and stable aggregation was induced within 20 minutes. On the contrary, rapid signaling via DP or DQ required prestimulation with either PMA or anti-sIg. Aggregation was temperature and energy dependent. [Ca2+] and [Mg2+] concentrations and an intact cytoskeleton were required while neither mRNA or protein synthesis were required. Furthermore, FACS analysis revealed that aggregation was not directly correlated with cell surface expression of HLA class II molecules. Our results demonstrate that aggregation was mediated through a protein tyrosine kinase (PTK)-dependent pathway that preceded activation of protein kinase C (PKC) and failure to generate either the PTK signal or the PKC signal prevented aggregation. The contribution of a tyrosine kinase was further demonstrated by the total inhibition of aggregation following treatment with an anti-CD45 mAb. PMID- 1429033 TI - Production and characterization of murine monoclonal antibodies recognizing HLA DQ polymorphisms obtained by immunizing mice with transfected L cells. AB - Two polymorphic anti-HLA-DQB1 mAbs, TM 902 and TM 903, have been produced by immunizing F1 mice (Balb/C x C3H) with HLA-DQ-transfected mouse L cells. Cytotoxic analysis on a panel of HLA-typed cell lines has shown that TM 902 reacts with all the DQB1* alleles except DQB1*0501, *0502, and *0503, and DQB1*0601, *0602, *0603, and *0604, whereas TM 903 reacts with the DQB1*0501, *0502, and *0503, DQB1*0601, *0602, *0603, and *0604, and DQB1*0401 and *0402 alleles. The same reactivity pattern has been confirmed by cytofluorimetric analysis. Indirect immunofluorescence with various class-II-transfected cell lines showed no binding of both mAbs to the DR or DP products, suggesting their reactivity to the DQ products. The use of transfectants expressing HLA-DR/DQ heterodimers demonstrates that TM902 and TM903 mAbs are both specific for the DQ beta chain. Comparison of the amino acid sequences of the DQ-beta chain suggests the involvement of residues 84-90 (QLELRTT) in the formation of TM902 epitope and of residues 54-55 (GR) in the formation of TM903 epitope. PMID- 1429034 TI - Analysis of HLA DP, DQ, and DR alleles in adult Italian rheumatoid arthritis patients. AB - We analyzed the distribution of DRB1, DQA1, DQB1, and DPB1 allelic variants in 48 rheumatoid arthritis (RA) patients, compared with 109 Italian random controls, using PCR amplification and hybridization with specific oligonucleotides. We confirm the previously reported increase of DR4 specificity, in comparison with healthy Italian individuals. In particular, we find a statistically significant positive association of DRB1*0401 and DRB1*0404 alleles with RA. However, when we compare the DR4+ groups, none of the DRB1*04 alleles is increased in the RA group. By sequence analysis, performed on 10 patients, we demonstrate that the DRB1*04 genes of RA show no difference from the DRB1*04 sequences previously published. From the molecular analysis of the other DRB1 polymorphic variants, we find a trend of positive association of DRB1*0101 in DR4-negative patients versus DR4-negative healthy controls and, in the group of DR4-negative and/or DR1 negative patients, a similar increase of DRB1*06. Also, we observe in RA patients a statistically significant increase of DQA1*0301 and DQB1*0302 accompanied by a significant decrease of DQA1*0201, DQA1*0501 and DQB1*0201. Finally, from the analysis of DPB1 gene, it can be assessed that the distribution of DPB1 alleles does not differ significantly between RA patients and healthy controls. PMID- 1429035 TI - Relative contribution of HLA-DQA and -DQB alleles to predisposition to insulin dependent diabetes mellitus. AB - The presence of DQA and DQB alleles conferring protection or susceptibility was assessed in a panel of 39 insulin-dependent diabetes mellitus patients and 39 healthy control subjects from the central highland of Ethiopia. The results were grouped into three entities: a combination of alleles conferring susceptibility, a group conferring protection, and a group without any apparent HLA-DQ or -DR predisposition to insulin-dependent (type 1) diabetes mellitus (IDDM). Statistical analysis revealed that the relative risk of the first group is 64.1. If a similar approach is applied to the data on a study in caucasoid IDDM patients and controls of Kahlil and colleagues, the pattern is fully consistent with the data presented here, with an extraordinarily high relative risk (RR 258.2). It will be of interest to study whether this subdivision is reflected or supported by clinical or etiologic differences of the disease. The predictive value of susceptibility phenotypes appears to be more accurate by the proposed subdivision. Furthermore, in combination with islet-cell antibody analysis, assessment of genotype will permit more accurate identification of prediabetic individuals to be entered in clinical trials. PMID- 1429036 TI - Contribution of a single DQ beta chain residue to multiple sclerosis in French Canadians. AB - Putative disease susceptibility and resistance HLA class II alleles were studied in 78 French Canadian multiple sclerosis (MS) patients and 79 controls by using sequence-specific oligonucleotide probes to analyze in vitro amplified DNA (PCR SSOP) typing). In this relatively homogeneous ethnic group, MS was positively associated with DRB5*0101, DQB1*0602, and DQA1*0102 and negatively associated with DQB1*0301. The strongest disease association was with DQB1*0602. Complete DQB1 typing of these individuals, plus RFLP DQ beta typing of an additional five patients showed that 98% of patients compared with 73% of controls carry DQB1 alleles encoding leucine at residue 26. In contrast, 16% of patients compared with 38% of controls carry DQB1 alleles encoding tyrosine at the same residue, and 22% of patients versus 44% of controls carry DQB1 alleles encoding glycine at residue 26. The positive disease correlation was confirmed with SSO probes designed to hybridize to codons for amino acids 22-27 of DQB1*0602, 0603, 0604, 0302, 0303 or to codons for amino acids 25-31 of DQB1*0201; all of these alleles encode Leu 26. These findings suggest that DQ beta chain polymorphisms at a single residue contribute to the development of MS in the French Canadian population. PMID- 1429037 TI - Apparent HLA DR triplet due to the coexpression of a DRB5-encoded molecule on a DR1 haplotype. AB - HLA DR1 molecules are coded by a single polymorphic DRB1 gene. We have observed rare DR1 cells in one Caucasoid family and three unrelated individuals that also reacted with some anti-DR2 sera. Since the second DR antigen was normally expressed, these cells appeared as triplets. Contrary to serology, the cells were not typed by HTCs defining Dw2, Dw12, and Dw21. Further investigations on these unusual DR1+2* haplotypes were conducted by DNA oligotyping and by sequencing of the DRB first-domain exon. The results showed that these DR1 haplotypes, besides their DRB1*0101 allele, carried also a DRB5*0101 allele. PMID- 1429038 TI - HLA class II expression on human epidermal Langerhans cells in situ: upregulation during the elicitation of allergic contact dermatitis. AB - An immunoelectron-microscopic technique was applied to investigate the localization of molecules that are involved in the elicitation of allergic contact dermatitis in human epidermal cells in situ. Langerhans cells in the epidermis of lesions showed a strongly increased cell surface expression of HLA class II molecules as compared with normal skin. In addition, a high number of intracellularly located HLA class II molecules were present in Langerhans cells of lesional epidermis, suggesting increased biosynthesis of these molecules during the elicitation process. In contrast, no differences in the expression of CD1a by Langerhans cells was observed between normal and lesional skin. Frequently, the Langerhans cells were found in close apposition to mononuclear cells, which also exhibited a strong cell surface HLA class II expression. The number of Birbeck granules that are characteristic intracellular Langerhans cells organelles was increased in lesional Langerhans cells as compared with normal skin Langerhans cells, which may correlate with the activated state of lesional Langerhans cells. These Birbeck granules were always HLA class II or CD1a negative. The increased synthesis and expression of HLA class II molecules on the cell surface of Langerhans cells suggests a direct role for these HLA class II molecules in the elicitation process of allergic contact dermatitis. PMID- 1429039 TI - HLA-DR,DQ sequence polymorphisms in Polynesians, Micronesians, and Javanese. AB - The origins of the Polynesians remain an enigma. Linguistic reconstructions of proto-Austronesian languages suggest a shared origin for Polynesians, Micronesians, and Javanese with dispersal from northern Borneo and Sulawesi. Analysis of 810 chromosomes for nucleotide sequence polymorphism at HLA-DRB1, DRB3, DRB5, DQA1, and DQB1 loci in Polynesian (Rarotonga, Western Samoa, and Niue), Micronesian (Nauru and Kiribati), and Javanese populations showed virtually no overlap of HLA class II haplotypes between contemporary Polynesians and Javanese. Further, there were marked differences in population distributions of some HLA-DRB1 alleles that could not be distinguished in earlier serologic or restriction fragment length polymorphism (RFLP) studies, e.g., for DR12, DRB1*1201 had a frequency of 15%-30% in Polynesians (1% in Micronesians and Javanese), whereas DRB1*1202 had a frequency of 28%-38% in Micronesians and 51% in Javanese (1% in Polynesians). A novel DR6-related allele, DRB1*1408, was found in all three Polynesian study populations. The Polynesian HLA class II genetic repertoire is not readily derived from the island Southeast Asian gene pool. PMID- 1429040 TI - Sequence variation in Japanese HLA-DRw8 specificity. AB - There are four DRw8 haplotypes with different DQ alleles in Japanese: DRw8-DQw6 (w1), DRw8-DQw4, DRw8-DQw8(w3), and DRw8-DQw7 (w3). We previously reported the nucleotide sequence of DRB1 gene of DRw8-DQw6(w1) and it was named DRB1*08032. The nucleotide sequences of the other DRw8 DRB1 alleles and their correspondence to internationally recognized DRw8 subspecificities were still unclear. We have cloned these DRB1 genes and determined the nucleotide sequences. The comparison of the sequences with the published sequences revealed that the differences were occurred at two amino acid positions, and these four haplotypes are classified in two groups: (a) DRw8-DQw6(w1) and DRw8-DQw7(w3), and (b) DRw8-DQw4 and DRw8 DQw8(w3). The DRB1 molecules of DRw8-DQw6(w1) and DRw8-DQw7(w3) have Ser57 and Ile67, and those of DRw8-DQw4 and DRw8-DQw8(w3) have Asp57 and Phe67. The former has the same sequence as that of DRB1*08032, and the latter is same as that of DRB1*0802. The classification corresponds to the serologic subtyping, which divides DRw8 into DR8.1 and DR8.2, reported in the 10th Japan HLA Workshop. PMID- 1429041 TI - Transplantation tolerance in heart transplant recipients as demonstrated by unresponsiveness in cell-mediated lympholysis. AB - Transplantation tolerance or adaptation to an allograft is associated with unresponsiveness to donor-specific transplantation antigens measured in in vitro cell-mediated lympholysis (CML). We here demonstrate in a longitudinal follow-up that CML nonreactivity develops in seven of ten patients following heart transplantation. The first manifestation of this nonreactivity manifested between 3 and 27 months after transplantation. CML nonreactivity correlated with time after transplantation and the percentage of activated lymphocytes in peripheral blood. CML nonreactivity was also associated with good graft function, i.e., in condition of nonresponsiveness patients did not manifest acute rejection. The only exception was seen in one patient in whom the immunosuppressive therapy was strongly reduced. A more detailed evaluation of this patient indicated that the underlying mechanism for CML nonreactivity is clonal anergy or active suppression of the alloreactive cells. PMID- 1429042 TI - Peptide-induced proliferation and lymphokine production in human T cells in the absence of antigen-presenting cells: role of T-cell activation state and costimulatory signals. AB - The role of T-lymphocytes as antigen-presenting cells (APCs) for other T cells was investigated. Activated rabies-virus-specific human T-cell clones were shown to present peptide to class II major histocompatibility complex (MHC)-restricted T cells of a different fine specificity, resulting in lymphokine production and cell proliferation. Furthermore, purified and activated antigen-specific T cells could produce lymphokines and proliferate as a result of the addition of antigenic peptide in the absence of APC. The functional response of T cells to peptide in the absence of APC was amplified by the addition of phorbol ester (PMA) and was inhibited with antibodies specific to class II MHC or to the CD2 molecule. Experiments performed in single-cell suspension cultures using semisolid medium prepared with 1% agar demonstrate that T-cell proliferative and lymphokine responses to peptide both in the presence and absence of APC require the interaction of T-cell antigen receptor (TCR) molecules with class II MHC peptide complexes on different cell surfaces (cell-cell contact). On the other hand, peptide self-presentation, which occurs by the binding of TCR with class II MHC-peptide complexes on the same cell surface (at the single-cell level), resulted in T-cell activation (i.e., high expression of surface CD2, CD25, and HLA-DR molecules), without proliferation or lymphokine secretion, a pattern observed in the induction of T-cell anergy by antigen. The results are discussed in terms of the role of class II MHC molecules on activated T-lymphocytes, which enable these cells to function as "professional APC" in the development of T-cell regulatory networks. PMID- 1429043 TI - Silent allelic variants of a T-cell receptor V beta 12 gene are present in diverse human populations. AB - Amino acid substitutions in variable regions of the T-cell receptor (TCR) can alter T-cell reactivity; however, relatively little is known about the extent of allelic variation in human TCR coding sequences. In the present studies, coding region variation in the human TCR V beta 12.2 gene was examined in detail. Virtually the entire V beta 12.2 coding region was screened for nucleotide substitutions by single-stranded conformational polymorphism analysis. Four alleles were identified in a sample population of 90 unrelated people from diverse genetic backgrounds. Three of the alleles were common, with estimated frequencies of 0.32, 0.47, and 0.20. Sequence analyses revealed that variation between the alleles was confined to three single-base differences in codons 24, 31, and 45; none of these changes altered the amino acid sequence. No evidence for other coding region differences in this gene were found. This analysis suggests that coding region variation in V beta 12.2 is limited, and amino acid sequence is highly conserved. PMID- 1429044 TI - Flow-cytometric analysis of immune cell populations in human decidua from various types of first-trimester pregnancy. AB - We undertook an investigation in which flow cytometry was used to characterize immune cell populations in the decidua of first-trimester normal pregnancies, spontaneous abortions, and ectopic pregnancies in comparison to the nonpregnant endometrium to demonstrate how the proportions of immunocompetent cell populations at the fetomaternal interface are influenced by the presence and state of a fetoplacental allograft. No significant differences were found in the decidua of the different types of first-trimester pregnancy in the proportions of the CD45+, CD14+, CD3+, CD4+, CD8+, CD19+, CD3-/CD16+ and/or CD56+, CD3+/CD16+ and/or CD56+, CD4+/Leu-8+, CD4+/Leu-8-, CD8+/CD11b+, CD8+/CD11b-, and CD3+/HLA-DR decidual leukocyte subsets. However, the percentage of decidual CD3+/HLA-DR+ cells, which are characteristic of activated T cells, was significantly higher in spontaneous abortions than in normal pregnancies (p less than 0.05). This suggests that the accumulation of decidual leukocytes may be regulated mainly by hormones and/or cytokines rather than by the presence and state of an intrauterine conceptus and that on/off-switching of activation of decidual T cells may be associated with successful maintenance of the implanted embryo. PMID- 1429046 TI - Paralymics offer athletes--and DOs--new challenges. PMID- 1429045 TI - Autologous graft-versus-host disease: a novel approach for antitumor immunotherapy. AB - Autologous bone marrow transplantation (BMT) is a therapeutic option for the treatment of lymphohematopoietic malignancies and solid tumors. Despite the intensive cytoreductive therapy, however, the rates of tumor recurrence after autologous BMT remain unacceptably high. Current studies suggest that the administration of cyclosporine (CsA) disrupts the reconstitution of self tolerance following autologous BMT leading to the induction of an autoimmune graft-versus-host disease (GVHD). Studies in a rat tumor model and preliminary clinical trials suggest that this autoimmune or autologous GVHD provides a significant antitumor effect. Moreover, the antitumor effect of autologous GVHD can be enhanced by administration of gamma-interferon, which upregulates the antigen recognized by the autoreactive effector cells of autologous GVHD. These studies indicate that the induction of an autoimmune GVHD after autologous BMT may be a promising immunotherapeutic approach for treatment of certain neoplastic diseases. PMID- 1429047 TI - Familial glomerular disease: it's all in the genes. PMID- 1429048 TI - Familial glomerular disease with asymptomatic proteinuria and nephrotic syndrome: a new clinical entity. AB - Seventy-three members of a 100-member kindred with asymptomatic proteinuria, nephrotic syndrome, and progressive renal failure were studied. Of those studied, 11 members had progressed to end-stage renal disease and seven had significant proteinuria (greater than 1 g/24 hours) with normal renal function. The genetic mode of inheritance was autosomal dominant with variable penetrance and expressivity. Histopathologic changes were variable but included focal segmental glomerulosclerosis and diffuse glomerulosclerosis. Renal failure usually occurred in the fifth decade of life. The most consistent clinical finding was proteinuria without microscopic hematuria or other significant urinary sediment elements. This disease differed from Alport's hereditary nephritis and congenital nephrotic syndrome in age of onset, urinary findings, and associated conditions, that is, nerve deafness. The hereditary proteinuria and nephrotic syndrome described in this kindred represents another facet in the spectrum of hereditary renal disease. PMID- 1429049 TI - Adult respiratory distress syndrome: a review for the clinician. AB - Adult respiratory distress syndrome is a common respiratory problem with a wide array of precipitating causes and an overall mortality rate of more than 50%. Signs on physical examination tend to be nonspecific as do laboratory findings associated with the syndrome. Because of its diverse etiology, there is no one specific treatment for adult respiratory distress syndrome. Therapy is primarily supportive and centers around the use of mechanical ventilator support. The authors discuss the pathogenesis and management of this syndrome together with some of the newer approaches to mechanical ventilation. PMID- 1429050 TI - Therapeutic considerations: lower respiratory tract infections in smokers. AB - Tobacco smoke can alter both the structural and the immunologic defenses of the lungs against infection. The gases from smoke can also inhibit repair of the damages they create. Smokers have been found to have increased bacterial adherence to the respiratory tract, decreased IgA and IgG, and a decrease in vital capacity two to three times greater than that of nonsmokers. These and other respiratory tract alterations put smokers at an added disadvantage when acute lower respiratory tract infections strike. A history of smoking influences the diagnosis of respiratory tract infections because smokers are more prone than nonsmokers to infection by certain organisms. The major causes and characteristics of lower respiratory tract infections, methods of outpatient diagnosis, and the pros and cons of various modes of therapy are discussed. PMID- 1429052 TI - The family physician's role in the continuity of care of the HIV-infected patient. PMID- 1429051 TI - Therapeutic drug monitoring: lithium levels. AB - Lithium has been used in the treatment of mania since 1949. Although its effectiveness is well recognized, the mechanism by which it stabilizes manic behavior is not well understood. In addition, it has some serious toxic properties combined with a narrow therapeutic range. For this reason, monitoring of serum lithium levels is mandatory. Suggested mechanisms of action and protocols for monitoring of serum levels are presented. PMID- 1429053 TI - Evaluating an intern/residency program. AB - When faced with the task of program evaluation, many directors of medical education may find themselves overwhelmed. This article presents suggestions for conducting an evaluation, including the six basic elements to consider before embarking on such an undertaking. With an emphasis on selecting a model framework as a guide for conducting a program evaluation, this article examines one model- Stufflebeam's CIPP model--in depth. PMID- 1429054 TI - Retained fetal scalp monitoring lead discovered in the wall of the jejunum. AB - The retention of a foreign body following surgery is a longstanding and dreaded problem. We report the retention of a fetal scalp monitoring lead that was embedded in the wall of the patient's jejunum and discovered 2 years after cesarean section. In reviewing the American medical literature, we believe this case is, perhaps, unique. The treatment of this entity is discussed as well as ways to help to prevent it. PMID- 1429055 TI - Aortic dissection in acute pancreatitis. AB - Extrapancreatic fluid collections are frequently seen in acute pancreatitis. Vascular damage with life-threatening hemorrhage is also a known complication. In the case report presented, we include documentation by computed tomography of an apparent abdominal aortic wall dissection by fluid in a patient with acute pancreatitis. Conservative therapy resulted in complete resolution without hemorrhage or aneurysm formation. PMID- 1429056 TI - Anomalous origin of the left main coronary artery from the right anterior aortic sinus. AB - Anomalous origin of the left main coronary artery from the right sinus of Valsalva is an uncommon problem, occurring in four distinct patterns. When the left main coronary artery passes between the aorta and the pulmonary trunk, acute myocardial ischemia or sudden death may occur. Angiography is required in establishing a diagnosis. Surgical correction or bypass surgery are sometimes indicated. The authors report two cases of anomalous origin of the left main coronary artery and discuss the anatomic variants, clinical significance, and technical considerations in both diagnosis and management. PMID- 1429057 TI - Mirizzi syndrome (hepatic duct obstruction). AB - The Mirizzi syndrome is an uncommon cause of obstructive jaundice. In 1948, Mirizzi characterized a syndrome in which common hepatic duct obstruction occurs because of impacted stones in the gallbladder neck or cystic duct. The authors report a case demonstrating this syndrome. They discuss the radiographic features and report the features found on a computed tomographic cholangiogram that have not been previously described. Computed tomography-cholangiography may be helpful in evaluating patients with suspected Mirizzi syndrome. PMID- 1429058 TI - Primary laryngeal and nasal septal lesions in pemphigus vulgaris. AB - Synchronous laryngeal and nasal septal lesions in pemphigus vulgaris are rare. The authors report a case of pemphigus vulgaris in an elderly man who was seen with lesions of the supraglottic larynx and nasal septum. The classic skin changes of pemphigus eventually developed, and the patient responded to daily treatments of 80 mg of prednisone. Steroids and immunosuppressive agents remain the treatment of choice, but a favorable prognosis is still dependent on early diagnosis and institution of therapy. PMID- 1429059 TI - Male breast carcinoma: clinical experience in a suburban community. AB - Male breast cancer is difficult to study because it occurs infrequently, accounting for 1% of all breast carcinoma. Breast cancer occurs 10 years later in men than in women, and its presentation parallels that in women. The authors retrospectively review 13 cases of male breast cancer occurring over a 20-year period in four community hospitals. Treatment methods paralleled those used for female cancer patients. Surgery, primarily radical mastectomy, was performed in all patients. In the eight patients in whom hormone receptor assays were obtained, all tests were positive for estrogen receptors, progesterone receptors, or both. Metastases were diagnosed in five patients during follow-up. The longest disease-free survival has been 10 years. Similarities and differences regarding male and female breast cancer are discussed as are the diagnosis and management of men with this disease. PMID- 1429060 TI - Update on monoclonal antibody therapy in the gram-negative sepsis syndrome. AB - Two multicenter controlled clinical trials of genetically engineered monoclonal antibodies directed against endotoxin, a potent mediator of inflammation in the gram-negative sepsis syndrome, were recently reported in the medical literature. One of these antiendotoxin antibodies was derived from a murine (mouse) source, and the other antibody was derived mainly from a human source (nebacumab [negative bacteria human monoclonal antibody]). This article reviews recent literature concerning the use of these agents in the treatment of gram-negative sepsis syndrome. It also projects economic assessment data regarding the use of nebacumab in the United States. PMID- 1429061 TI - The lupus anticoagulant and antiphospholipid antibodies. AB - Antiphospholipid antibody syndromes are primarily manifested as unexplained thrombotic events. Several antiphospholipid antibodies have been identified, the lupus anticoagulant being the most recognized. Considerable confusion surrounds this "anticoagulant," which is highly correlated with an increased risk of thrombosis. Several assays have been designed for the detection of antiphospholipid antibodies. There are limitations on their efficacy and interpretation requires judgment. Treatment strategies for the clinical manifestations of the antiphospholipid antibody syndrome are being developed. The explosive rise in the volume of literature dedicated to this topic will assure new and improved modalities for evaluation and treatment. PMID- 1429062 TI - Hepatitis testing update. AB - During a 25-year period, four types of hepatitis-causing virus have been identified and can now be evaluated serologically. This final article in this clinical laboratory medicine series reviews routes of virus transmission and persistence and the availability of tests. PMID- 1429063 TI - Workup of a patient with newly diagnosed HIV infection. AB - This monthly series was developed from the AOA Task Force on AIDS Writers' Workshop, held August 16 to 18, 1991, in New York. The workshop was sponsored by an education grant from Burroughs Wellcome. It will provide brief clinical updates and perspectives on the human immunodeficiency virus (HIV). Readers may request tear sheets from the AOA editorial offices. PMID- 1429064 TI - Suggestions for clinicians providing--and residents seeking--feedback. AB - As a form of verbal or nonverbal communication intended to promote learning, feedback plays an important role in the medical training process. More often than not, however, feedback is given--and received--inappropriately by both clinicians and residents, respectively. This article outlines common types of instructional feedback, their inherent advantages and disadvantages, and suggests ways in which clinicians and residents may incorporate feedback effectively in a residency/training program. PMID- 1429065 TI - Invasive aspergillosis of the sphenoethmoidal sinuses in an immunocompetent host. AB - Fungal infections of the nose and paranasal sinuses are uncommon; Aspergillus is the most frequently isolated fungal pathogen. Invasive aspergillosis is commonly seen as an opportunistic infection in the immunocomprised, debilitated host. Whereas fulminant infection in the otherwise healthy patient is rare, in the immunocompetent host with persistent signs and symptoms of sinusitis despite appropriate medical management, aspergillosis should be considered. Treatment of paranasal sinus aspergillosis requires correction of immunologic deficits, if possible; aggressive surgical debridement to provide adequate drainage and aeration of the sinuses; and adjunctive antifungal chemotherapy. The authors present an unusual case of invasive aspergillosis of the paranasal sinuses in an immunocompetent host. PMID- 1429066 TI - Cerebral emboli from the 'stump' of a totally occluded carotid artery: surgical management. AB - The obstructing thrombus in a totally occluded internal carotid artery may act as a source of cerebral emboli. These emboli traverse the external carotid and ophthalmic arteries and enter the intracranial circulation via retrograde collateral pathways. Surgical treatment can result in complete abatement of symptoms in selected patients. The authors describe internal carotid "stump" syndrome in a 47-year-old man and discuss the options for surgical management. PMID- 1429067 TI - Clinical improvement of the myopathy in eosinophilia-myalgia syndrome with steroids and rehabilitative therapy. AB - The authors report a case of eosinophilia-myalgia syndrome with a progressive neuromyopathy. Progressive weakness, myalgia, and dermatitis developed in the patient described after chronic ingestion of high-dose L-tryptophan for insomnia. Laboratory, electrophysiologic, and muscle biopsy results support the diagnosis of an inflammatory myopathy consistent with that of eosinophilia-myalgia syndrome. The patient's weakness led to wheelchair dependency. A review of the literature regarding this disorder shows inconsistent results with steroid and other modes of therapy. After a course of high-dose steroids with long-term tapering and vigorous inpatient and outpatient rehabilitation, the patient was able to walk and function independently within 2 months. PMID- 1429068 TI - Reorganizing 'traditional' case presentation enhances learning, clinical experience. PMID- 1429069 TI - Taking a sobering look at teenage alcohol use. PMID- 1429070 TI - Generating dialogue concerning cranial plate motion. PMID- 1429071 TI - A virus has been found. PMID- 1429072 TI - Osteopathic medicine: 100 years in the making. PMID- 1429073 TI - Roentgenographic documentation of atlanto-occipital sidebending. AB - It is assumed that the atlas (C1) glides superiorly and laterally along the occipital (C0) condyle during translatory motion of the head in the opposite direction. To provide roentgenographic documentation, a translatory test of atlanto-occipital (C0-C1) motion was performed to the left and to the right on a healthy, asymptomatic volunteer subject. Roentgenographic examination was made at the extreme in each direction. The films indicate the change in atlantal position relative to the occiput and support the assumption. A translation of the head in the coronal plane to test for atlanto-occipital joint mobility is described. PMID- 1429074 TI - The evolution of osteopathic manipulative technique: the Spencer technique. AB - The Spencer technique is a standardized series of shoulder treatments with broad application in diagnosis, treatment, and prognosis. The evolution of this technique is traced from 1916 to date to try to identify factors in the development of manipulative methods. Few suggestions about the basic steps to be followed in developing any new manipulative technique were seen. Of chief importance were changes in sequence, the addition of steps, and the combination of one technique with another, as in the addition of muscle-energy methods to each step. One change, accidentally introduced in the 1970s, displaced a critical step in the procedure. The principal element guiding the development of the Spencer technique appears to be clinical necessity interpreted in terms of anatomy and pathology. PMID- 1429075 TI - Starting therapy for an HIV-infected patient. AB - This monthly series was developed from the AOA Task Force on AIDS Writers' Workshop, held August 16 to 18, 1991, in New York. The workshop was sponsored by an education grant from Burroughs Wellcome. It will provide brief clinical updates and perspectives on the human immunodeficiency virus (HIV). Readers may request tear sheets from the AOA editorial offices. PMID- 1429076 TI - Alleviating stress in residency training through enhanced communication: a practical guide. AB - Stress is an inherent component of residency training and its effect on healthcare provided is well documented. Although stress-related signs and symptoms are easily recognized, residents and trainers are likely to ignore them- until a crisis occurs. Based on the theory that good communication alleviates stress, the "I" Language Model, discussed in this article, is designed to enhance communication between residents and their superiors, colleagues, and families. As such, it is meant to provide one means of intervention before stress affects the resident's on-the-job performance. PMID- 1429077 TI - Manipulation with the patient under anesthesia. AB - Manipulation while the patient is under anesthesia is an old, widely recognized procedure in musculoskeletal medicine. It is used for treating acute and chronic musculoskeletal conditions with significant biomechanical dysfunction unresponsive to conservative therapy. The procedure is helpful when muscle spasm and irritability preclude success without anesthetization of the patient. Safety and effectiveness are favored by appropriate selection of patients, knowledge of indications and contraindications, suitable anesthetic, and services of a qualified physician trained in structural diagnosis and manipulative technique. A team approach is recommended. To illustrate effective use of the procedure, a classic case is described. PMID- 1429078 TI - Empty sella syndrome associated with partial hypopituitarism (visualized on MRI scan). AB - The empty sella syndrome has become a rather frequent finding in magnetic resonance imaging (MRI) scanning. The usual presentation of empty sella syndrome involves an incidental finding on a computed tomography scan or an MRI scan. It is unusual to find empty sella syndrome associated with hypopituitarism. The authors describe such an unusual finding in a 54-year-old nulliparous woman. PMID- 1429079 TI - High activity iodine-125 interstitial implant for gliomas. AB - A total of 307 adult patients with glioma were treated with high-activity removable iodine-125 interstitial brain implants at the University of California at San Francisco from December 1979 to June 1990. Recurrent gliomas underwent brain implant alone whereas previously untreated (primary) tumors underwent brain implant boost after external beam radiotherapy. Of these patients, 106 had primary glioblastoma multiforme, 68 had primary non-glioblastoma glioma, 66 had recurrent glioblastoma multiforme and 67 had recurrent nonglioblastoma glioma. Median follow-up for living patients was 143 weeks. Median survival from diagnosis for primary glioblastoma multiforme and high and low grade nonglioblastoma glioma was 88 weeks, 142 weeks, and 226 weeks, respectively. Median survival measured from the date of implant for recurrent glioblastoma multiforme and high and low grade nonglioblastoma glioma was 49 weeks, 52 weeks, and 81 weeks, respectively. Ninety-two percent of patients had no toxicity or transient acute side effects. Severe acute toxicity was seen in 6% of patients, life threatening acute toxicity in 1% of patients, and fatal toxicity in less than 1% of patients. Forty percent of patients with malignant glioma underwent reoperation at a median of 33 weeks after brain implant, with tumor found in 95% of specimens at reoperation. This large experience demonstrates that interstitial implant is well-tolerated and prolongs survival in patients with primary and recurrent glioblastoma multiforme, as evidenced by the 3-year survival rates of 22% and 15%, respectively. PMID- 1429080 TI - Interstitial brachytherapy for newly diagnosed patients with malignant gliomas: the UCSF experience. AB - Although interstitial brachytherapy appears to be effective in treating recurrent malignant gliomas, it has been studied less extensively in patients with newly diagnosed tumors. To examine the effect of this treatment when used at the time of primary diagnosis, we retrospectively reviewed the records of 88 patients who received temporary interstitial implants of 125I for newly diagnosed malignant gliomas. This brachytherapy was preceded by a course of external radiation therapy and followed, in some cases, by chemotherapy. The median duration of survival after the beginning of external radiation therapy was 87 weeks in patients with glioblastoma multiforme and 160 weeks in those with anaplastic gliomas. In 46% of patients with glioblastoma multiforme and 56% of those with anaplastic gliomas, a second operation was necessary to remove symptomatic radiation necrosis, recurrent tumor, or both. Our results support the conclusion that interstitial brachytherapy used at the primary diagnosis lengthens survival in selected patients with glioblastoma multiforme. However, the toxicity is significant in terms of the need for surgical resection of symptomatic necrosis. In patients with anaplastic gliomas, the toxicity associated with the treatment probably outweighs its advantages. PMID- 1429081 TI - Hyperfractionated radiation therapy for gliomas of the brainstem in children and in adults. AB - Between February 1984 and September 1990, 60 patients with brainstem gliomas were treated with hyperfractionated radiotherapy in the Department of Radiation Oncology at the University of California, San Francisco. Forty-one children (< or = 18 years) and 19 adults were treated with 100 cGy twice daily with 4-8 hr between doses. Thirty-one patients (21 children and 10 adults) received total doses of 66-72 Gy and 29 patients (20 children and nine adults) received 74-78 Gy. Median follow-up was 208 weeks for all patients (214 weeks for children, 157 weeks for adults). Twenty-three patients (14 children and nine adults) were alive at the time of analysis, surviving 59-359 weeks following treatment. Median actuarial survival was 73.6 weeks overall (72 weeks for children, 190 weeks for adults; p = 0.43). Survival at 12 and 24 months was 65% and 38%, respectively (63% and 32%, for children; 68% and 53% for adults). All patients had pretreatment magnetic resonance imaging by which tumors were classified as either focal or diffuse. No significant pretreatment prognostic factors for adults were identified. In children, significant favorable prognostic factors on univariate analysis were older age (p = 0.001), tumor location in thalamus or midbrain (p = 0.002), focal appearance on MRI scan (p < 0.001) and duration of symptoms > 2 months prior to treatment (p < 0.001). Thirty-five patients had tumor biopsies, leading to a diagnosis in 33 (22 children and 11 adults). Children with moderately anaplastic astrocytomas survived significantly longer than those with glioblastoma multiforme or unbiopsied tumors (p < 0.001). Only duration of symptoms > 2 months remained significant as a favorable prognostic indicator for children on multivariate analysis (p < 0.001). Survival was not significantly different for patients receiving < or = 72 Gy and those receiving > 72 Gy (p = 0.18). No subgroup of patients showed significantly better survival with the higher dose. These findings indicate that hyperfractionated radiotherapy is effective treatment for adults and a subgroup of better prognosis children with brainstem gliomas. There is a subgroup of pediatric patients with extremely poor prognosis for whom even this aggressive treatment does little to extend survival. We conclude that there is no benefit to increasing total dose above 72 Gy for any of the groups analyzed. PMID- 1429082 TI - Pediatric craniopharyngiomas: long term results of combined treatment with surgery and radiation. AB - From 1961 to 1981, 19 pediatric patients with craniopharyngiomas were treated with external beam radiation post surgery. Twelve underwent primary treatment while seven were treated for recurrence. Median follow-up is 21 years (range 8-28 years) with an overall 20-year survival of 62%. Twenty-six percent (5/19) developed disease recurrence following radiation. Of the multiple patient and treatment parameters analyzed, only initial disease status (i.e., primary vs recurrence), surgical extent, radiation dose, and treatment prior to routine use of CT scans (1961-1974) appeared to have major influence on patient outcome. The 20-year survival for those treated for primary disease was 78% versus 25% for those treated for recurrence. Fifty percent (3/6) of patients receiving tumor doses of < or = 5400 cGy developed recurrences versus 15% (2/13) in those receiving > 5400 cGy. Four of the five recurrences occurred in patients treated during the pre-CT era. Long term effects of treatment were analyzed. Surgical morbidity correlated strongly with extent of surgery. All patients who underwent total resection developed surgical sequelae. Radiation morbidity correlated strongly with radiation dose. The incidence of vascular or neurologic complications attributable to radiation were minimal, occurring in only two patients. Both received doses higher than that given with modern therapy. Long term results from this series are better than those reported with surgery alone. Use of modern surgical and radiation equipment/technique along with CT/MRI imaging should yield improved treatment results both in terms of lower recurrence and lower toxicity rates. PMID- 1429083 TI - Defining the role of radiosurgery in the management of brain metastases. AB - The role of stereotactic radiosurgery in the management of recurrent and newly diagnosed brain metastases was evaluated prospectively. From December 1988 to March 1991, 58 lesions in 40 patients were treated with accelerator-based stereotactic radiosurgery. All patients were followed for a minimum of 6 months or to death. The primary purpose was to determine the impact of radiosurgery on local control and its subsequent effects on quality of life. An overall tumor control rate of 82% with a complete response rate of 43% were achieved. As anticipated, the response rate for smaller tumors was substantially better than that for larger tumors (78% for lesions < 2 cm3; 50% for lesions > or = 10 cm3). Although the overall in-field progression rate was 18.5%, only 1/23 (4%) complete responders subsequently recurred. The in-field failure rate is highly comparable with recently published surgical data. Progression outside the brain was noted in two-thirds of patients. One quarter of the deaths were neurologic. The median survival for this minimally selected patient population was 6.5 months. Stereotactic radiosurgery was also associated with improved quality of life as measured by Karnofsky score, neurologic function, and steroid dependence. Long term steroid dependence was encountered in only four patients. We conclude that stereotactic radiosurgery can be used effectively in patients with brain metastases. In this series, a high tumor response rate was achieved which was associated with improved quality of life. PMID- 1429084 TI - The role of laminectomy in the combined treatment of metastatic spinal cord compression. AB - A retrospective analysis of clinical data concerning 140 patients with spinal cord compression is presented. Treatment consisted of a surgical decompressive laminectomy followed by radiation therapy in 127 cases. Primary radiation therapy supported by steroids was applied in only 26 cases. A dose of 30-40 Gy in 15-20 fractions was delivered to all patients. Treatment outcome was analyzed by comparing motor function (categories: no deficit, mild deficit ambulatory, paraparetic not ambulatory, paraplegic), sphincter function, and pain relief before and after treatment in both modalities. Following laminectomy and radiation therapy, 82% of paraparetic patients regained their ability to walk, sphincter function improved in 68%, pain relief was achieved in 88%. Following radiation therapy alone, 64% of paraparetic patients became ambulatory, 33% showed a normalization of sphincter function, and 72% became pain free. Our results indicate that laminectomy should play a major role in the treatment of patients with metastatic spinal cord compression. The decision as to the treatment of choice has to be made individually for each patient taking into consideration his general condition, life expectancy, and origin of the primary. PMID- 1429085 TI - Patterns of failure following combined modality therapy for esophageal cancer, 1984-1990. AB - From 1984-1990, 143 patients with squamous cell or adenocarcinoma of the esophagus were enrolled in a Phase I/II study of neoadjuvant chemotherapy followed by concurrent chemotherapy plus radiotherapy with or without subsequent esophagectomy. Patients received one cycle of Cisplatin or Carboplatin plus Etoposide for squamous cell carcinoma, or Cisplatin or Carboplatin plus 5FU for adenocarcinoma, followed by two cycles of the same chemotherapy given concurrently with 44-46 Gy over 5 weeks. Operable patients then underwent esophagectomy. Inoperable patients and those with positive surgical margins received additional irradiation (16-18 Gy). Twelve percent of the surgical group received preoperative radiotherapy doses > or = 50 Gy. Seventy-two percent (103) had clinical Stage I-III tumors and 28% (40) were clinical Stage IV (1983 American Joint Committee on Cancer criteria). Only clinical Stage I-III patients were analyzed with respect to patterns of failure. Isolated local failure occurred in 19/103 (18%) of clinical Stage I-III patients. Both local and distant relapse occurred in 15/103 (15%), and distant metastases alone occurred in 25/103 (24%). The 3-year actuarial rates of local and distant failures were 45% and 60%, respectively. Among the clinical Stage I-III patients who underwent surgery (n = 58) versus those who did not (n = 45), the 3-year actuarial local and distant failure rates were 30% versus 60% and 45% versus 45%, respectively. Multivariate analysis was performed to identify significant predictors of local control. For all clinical Stage I-III patients, treatment with surgery (p = 0.001) and with three or more cycles of chemotherapy (p = 0.02) were significant predictors of improved local control. Patients who underwent surgery were significantly younger and had a better performance status than those who did not. The improvement in local control with surgery did not translate into better survival, likely on account of a high operative mortality rate in older patients and those receiving > or = 50 Gy preoperatively. We conclude that local control remains poor with concurrent chemotherapy + radiotherapy for esophageal cancer. The addition of surgery improved local control, but distant metastases remain a problem both in this group of patients as well as those treated without esophagectomy. Efforts to improve local control appear warranted, but it remains to be demonstrated that improved local control translates into improved survival in esophageal cancer because of a high rate of distant metastases in patients whose disease is controlled in the esophagus. PMID- 1429086 TI - Multimodality treatment programs for malignant pleural mesothelioma using high dose hemithorax irradiation. AB - The characteristic of malignant pleural mesothelioma is a tumor that grows by plate-like extension over the pleura, and invades adjacent tissues and organs. Radical surgical removal of the tumor is generally not possible, and most treatment regimens involve combined chemotherapy and radiotherapy, as well as debulking surgery. We have prospectively evaluated five locally-aggressive multi modality treatment programs, using different hemithorax irradiation schedules and chemotherapy regimens. One hundred patients with confirmed malignant pleural mesothelioma entered the study between 1977 and 1989. The treatment programs, which can consecutively, were: I, 20 Gy (10 x 2 Gy) to the hemithorax + CYVADIC (cyclophosphamide 500 mg/m2 d 1, vincristine 1 mg/m2 d 1 and 5, adriamycin 40 mg/m2 d 1 and dacarbazine 200 mg/m2 d 1 and 5, several cycles before and after irradiation); II, 55 Gy (25 x 2.2 Gy) to the hemithorax + 15 Gy (6 x 2.5 Gy) to the tumor + CYVADIC (2 cycles before, 1 cycle during, and 2 cycles after irradiation); III, Mitoxantrone (14 mg/m2 q 28 d, < or = 6 cycles) followed by 70 Gy (56 x 1.25 Gy, twice a day); IV, 4-Epirubicin (110-130 mg/m2 q 28 d, < or = 6 cycles) followed by 35 Gy (28 x 1.25 Gy twice a day) to the hemithorax + 36 Gy (9 x 4 Gy every 2 days) to the tumor; V, Etoposide (150 mg/m2 1, 3, 5 q 28 d) followed by 38.5 Gy (11 x 3.5 Gy) to the hemithorax. A new system for evaluating tumor response in pleural mesothelioma was applied. None of the combined treatment programs prevented local invasive growth or the spread of mesothelioma outside the hemithorax. The median survival time was slightly increased from 8 to 12 months for those patients who completed the protocol treatments, but progressive disease was the invariable outcome. Radiation pneumonitis and fibrosis were severe and compatible with results of total loss of lung function on the irradiated side. We conclude that data relating to therapeutic responses and treatment programs in malignant mesothelioma should be better correlated internationally, if the problems associated with the evaluation of treatment and the management of patients with mesothelioma are to be improved. PMID- 1429088 TI - Treatment of malignant gliomas with interstitial irradiation and hyperthermia. AB - A Phase I study of interstitial thermoradiotherapy for high-grade supratentorial gliomas has been completed. The objective of this trial was to test the feasibility and toxicity of hyperthermia induced by ferromagnetic implants in the treatment of intracranial tumors. The patient population consisted of 16 males and 12 females, with a median age of 44 years and a median Karnofsky score of 90. Nine patients had anaplastic astrocytoma while 19 had glioblastoma multiforme. Twenty two patients were treated at the time of their initial diagnosis with a course of external beam radiotherapy (median dose 48.4 Gy) followed by an interstitial implant with Ir-192 (median dose 32.7 Gy). Six patients with recurrent tumors received only an interstitial implant (median dose 40 Gy). Median implant volume for all patients was 55.8 cc and median number of treatment catheters implanted per tumor was eighteen. A 60-minute hyperthermia treatment was given through these catheters just before and right after completion of brachytherapy. Time-averaged temperatures of all treatments were computed for sensors located within the core of (> 5 mm from edge of implant), and at the periphery of the implant (outer 5 mm). The percentage of sensors achieving an average temperature > 42 degrees C was 61% and 35%, respectively. Hyperthermia was generally well tolerated; however, there have been 11 minor toxicities, which resolved with conservative management, and one episode of massive edema resulting in the death of a patient. In addition, there were three major complications associated with the surgical implantation of the catheters. Preliminary survival analysis shows that 16 of the 28 patients have died, with a median survival of 20.6 months from diagnosis. We conclude that interstitial hyperthermia of brain tumors with ferromagnetic implants is feasible and carries significant but acceptable morbidity given the extremely poor prognosis of this patient population. PMID- 1429089 TI - Hyperthermia enhances mitoxantrone cytotoxicity on human breast carcinoma and sarcoma xenografts in nude mice. AB - In this preclinical in vivo study, we measured antitumor response, local side effects and systemic toxicity of locally applied water-bath hyperthermia given alone or simultaneously with mitoxantrone (3 mg/kg b.w. i.v.; LD 10) on a human derived breast carcinoma (MX 1) or a human sarcoma (S 117) transplanted to female athymic (nude) mice. A single hyperthermia treatment at a tumor temperature up to 43 degrees C for 1 hr caused in both tumor lines only minor tumor regressions and transient tumor growth delay. However, the antitumor effect of mitoxantrone was significantly enhanced by local hyperthermia at 42 degrees C and particularly at 43 degrees C. In both tumor lines complete tumor regressions were achieved only if mitoxantrone was combined with hyperthermia. Undesired side effects and drug toxicity were not enhanced by hyperthermia. According to in vitro data and the results of the present in vivo study mitoxantrone seems to be a good candidate for clinical trials in combination with locoregional hyperthermia. PMID- 1429087 TI - Sarcoma therapy: functional outcome and relationship to treatment parameters. AB - PURPOSE: To systematically assess the functional outcome of patients treated with surgery and irradiation for extremity or truncal sarcomas, and to correlate this outcome with a detailed analysis of the radiation dose distribution and surgical technique. Conservative surgery and radiation therapy (RT) are known to provide excellent local control, but the relationship of technique to functional outcome requires further study. METHODS AND MATERIALS: Forty-one patients were treated for lower extremity (25 patients, 61%), upper extremity (8 patients, 19.5%), and truncal (8, 19.5%) sarcomas from 1983 to 1990. Most patients had malignant fibrous histiocytoma (15), liposarcoma (8), or aggressive fibromatosis (6). Age ranged from 13 to 85 years (median 54). All patients received RT and 39 (95%) had surgery. The mean total RT dose was 59 Gy (range 55.8-64.8 Gy). A protocol for functional assessment was devised and included a 4 point scale (0-3) for each of seven functional parameters (range of motion, fibrosis, edema, pain, skin changes, muscle strength, gait, or upper extremity performance). An aggregate score was obtained by adding the seven parameter scores and compared with both a patient and physician overall functional rating score (excellent, good, fair, poor). Based on this analysis, aggregate scores were defined as < or = 3 = excellent, < or = 8 = good, < or = 13 = fair, and > 13 = poor, with 21 as the worst possible score. The same orthopaedic surgeon and radiation oncologist independently examined and rated 22 patients. An additional 17 patients were evaluated by record review. The median time from completion of radiation therapy was 30.5 months (range 7-95 months). A computerized radiation therapy dosimetric analysis was performed on 34 patients. RESULTS: Local control was achieved in 39 patients (95%), including 6 with aggressive fibromatosis. The mean functional outcome score was 5.1 with a range of 0-16. 34 patients (83%) had good or excellent functional outcomes. The rating system demonstrated minimal interobserver variability. There was a positive relationship between volume irradiated to > or = 55 Gy and functional score, strength, fibrosis, and skin changes. Total dose independent of volume was significantly associated with skin changes. Increasing peak dose (hot spot dose) was associated with fibrosis and skin changes. More fibrosis developed as the volume of the peak dose increased. A portion of the joint was treated in 5/33 extremity patients and the entire joint in 24/33 (mean dose 55.8 Gy, range 45-65 Gy). Neither range of motion nor total functional score was correlated with joint dose. Edema and functional score were not related to either the volume or percent of limb spared (receiving < or = 40 Gy). The physician functional status ratings generally concurred with patient self-assessments. CONCLUSIONS: A system for functional assessment has been developed which is easily performed and provides detailed information about patient functional outcome. This system can be used to evaluate the morbidity of combined modality sarcoma therapy. Doses up to 65 Gy, even over joint spaces, are not associated with significant morbidity. Only a small volume treated to < or = 40 Gy is required to maintain good outcome. The most important parameter appears to be the volume treated to > or = 55 Gy. PMID- 1429090 TI - Radiosensitivity testing of human malignant gliomas. AB - Radiotherapy remains the main treatment modality for patients with malignant gliomas and is the only treatment which significantly prolongs survival. Clonogenic and tetrazolium based colorimetric assays (MTT) of early passage cultures have been performed following 2 Gy doses of x-rays in order to determine if in vitro radiosensitivity is a factor in response to treatment. Of 47 biopsies received, 39 were established in primary culture. A value of surviving fraction to 2 Gy (SF2) was obtained in 85% of growth assays and 64% of clonogenic assays. The mean SF2 value for the MTT was 0.56 which was significantly higher than the 0.42 obtained for the clonogenic assay. There was, however, reasonable qualitative agreement in assessing relative radiosensitivity/radioresistance (r = 0.7). Mean SF2 values for grade 3 tumors were 0.52 (MTT) and 0.35 (clonogenic) as against mean SF2 values of 0.63 (MTT) and 0.47 (clonogenic assay) for grade 4 tumors. In 24 patients with adequate follow-up, no direct correlation was found between SF2 and survival, although mean SF2 values for patients surviving greater than 18 months was significantly less (p = 0.01) than patients surviving less than 18 months as determined by the MTT assay. PMID- 1429091 TI - The effect of hyperfractionation on spinal cord response to radiation. AB - The T10-L2 level of the spinal cord of C3Hf mice was irradiated using a conventionally fractionated regimen of 2.0 Gy once daily or a hyperfractionated regimen of 1.2 Gy twice daily separated by 8 hr. After a fractionated dose of 24 60 Gy given by either regimen, a top-up dose of 15 Gy was given. Hind limb strength was then measured weekly for 15 months. The time to onset of paralysis was inversely associated with the total dose. Overall, the spinal cord was not spared by hyperfractionation to the extent predicted by the modified Ellis power law or the linear-quadratic model. The threshold dose for the development of paralysis was higher in the hyperfractionated than in the conventionally fractionated group. However, the latent period for paralysis and the dose producing hind limb paralysis in 50% of the mice (ED50) were not significantly different between the two regimens. The continuation of the process of sublethal damage (SLD) repair in the spinal cord beyond 8 hr after irradiation may have influenced these results. The slow component of SLD repair should be considered in the design of hyperfractionated or accelerated radiation therapy schedules for clinical use. PMID- 1429092 TI - The isoquinoline sulfonamide H7 attenuates radiation-mediated protein kinase C activation and delays the onset of x-ray-induced G2 arrest. AB - Protein kinase C activation by ionizing radiation in human tumor cell lines participates in the transcriptional activation of genes which may be associated with the phenotypic response of cells to x-rays. We gamma-irradiated cell line RIT-3 (radiation-induced human sarcoma) and quantified the phosphorylating capacity of protein kinase C. Protein kinase C activity increased rapidly and transiently in these cells. The selective protein kinase C inhibitor H7 attenuated radiation-mediated protein kinase C activation when added to cells prior to irradiation. To determine whether protein kinase C activation is associated with radiation-induced G2 arrest, we analyzed the cell cycle distribution of cells following gamma-irradiation. Following irradiation, RIT-3 cells rapidly progressed through G1 and S and subsequently underwent a dose dependent G2 arrest. At concentrations which are selective for protein kinase C inhibition, H7 delayed the onset of radiation-induced G2 arrest. However, there was no difference in the duration of G2 arrest following the addition of inhibitor as compared to cells irradiated without inhibitor. We propose that protein kinase C activation by ionizing radiation is associated with radiation mediated cell cycle regulation. PMID- 1429093 TI - The relationship between apoptosis and atrophy in the irradiated lacrimal gland. AB - Atrophy is generally considered to be a true late effect of radiation. However, in serous glands, atrophy was thought to be a consequential late effect because serous cells die within hours of irradiation and the apparent effects of atrophy are observed contemporaneously with radiation treatment. Therefore, to determine the pathogenesis of atrophy in serous glands, it is necessary to differentiate between parenchymal loss as a result of direct radiation death of serous cells and parenchymal loss as a result of serous cell death that is secondary to fibrosis, vascular damage, or precursor cell death. The lacrimal glands of 62 rhesus monkeys have been irradiated to single doses of 2.5 to 20 Gy and examined at intervals of 4 hr to 112 days postirradiation. Serous cells (nuclei) and acini were counted in at least 30 high power fields per (dose, time) point. At each dose and time of sacrifice, the average number of nuclei per acinus and the average number of acini per high power field were calculated. Also at each dose and time, the distribution of the number of nuclei per acinus was examined to determine how the frequency of acinar sizes changed as a function of irradiation. The number of cells per acinus appears to rise initially, but this is likely a result of the degranulated cells being physically smaller, yielding an artificially higher count. Within 4 days after 12.5 Gy, the average number of nuclei per acinus approaches control values and remains within the range of controls for at least 112 days. The number of acini per high power field decreases steadily for 30 days after 12.5 Gy. From 30 to 112 days, there is some recovery of this number, but it remains well below control values. At 24 hr, the number of nuclei per acinus shows a distinct dose response up to 20 Gy. However, at 30 days there is no evidence of a dose response for this parameter. These results indicate that even though serous cells die in significant numbers within hours of irradiation, the atrophy of the lacrimal gland (and by extension, the parotid gland) is a result of the death of the serous stem cell or precursor. Consequently, protection of serous cells from radiation apoptosis will not diminish serous gland atrophy. PMID- 1429094 TI - Sensitization processes in human tumor cells during protracted irradiation: possible exploitation in the clinic. AB - Recent studies documenting the response of several human tumor cell lines to protracted, continuous irradiation and to acutely delivered radiation, suggest that tumor control may be enhanced with a tumor therapy combining external beam fractionated therapy and protracted irradiation from radiolabeled antibodies. We have evaluated the cytotoxic effect of continuous, protracted irradiation (0.005 Gy/hr to 0.50 Gy/hr) and acutely delivered high-dose-rate irradiation (1.0 Gy/min) on monolayer cultures of human tumor cell lines. Colony formation in these studies was analyzed by the seven-parameter simulation model of Dillehay. Additionally, for some cell lines, cultures were challenged during irradiation with an acute dose of 2.5, 5.0, 7.5 or 10.0 Gy at high-dose-rate. Results from these various studies indicate an altered cellular radiosensitivity occurs for some cell lines during protracted irradiation. At least two mechanisms have been identified that underlie this altered radiosensitivity. One mechanism, G2B, associated with redistribution within the cell cycle, has been previously described by Mitchell and others, and is associated with the phenomenon termed "the inverse dose-rate effect". The other mechanism is only observable following a challenge by acute high-dose-rate irradiation. We have termed this phenomenon "protracted-exposure-sensitization." The characteristics of these two mechanisms are discussed from the perspective of clinical therapeutic exploitation of combined external beam fractionated therapy and radiolabeled immunoglobulin therapy. PMID- 1429095 TI - Immunophenotype predicts radiation resistance in T-lineage acute lymphoblastic leukemia and T-lineage non-Hodgkin's lymphoma. AB - In the preclinical arm of our study, the radiobiologic features of primary malignant cells from newly diagnosed and relapsed T-lineage acute lymphoblastic leukemia/non-Hodgkin's lymphoma patients were analyzed using clonogenic assays. A marked heterogeneity existed relative to the intrinsic radiation sensitivity of clonogenic T-lineage ALL/NHL cells from 42 patients. The mean SF2 (surviving fraction at 200 cGy) and alpha values (initial slope of the survival curve) were 0.36 +/- 0.04, and 0.558 +/- 0.079 Gy-1. Fourteen cases had SF2 values of > or = 0.50 and alpha values of < or = 0.2 Gy-1, consistent with a marked intrinsic radiation resistance at the level of clonogenic leukemia/lymphoma cells. Of these 14 radiation resistant cases, 12 were CD3+. Furthermore, the SF2 and D0 values of the 28 CD3+ cases were significantly higher than the SF2 and D0 values of the 14 CD3- cases (SF2: 0.441 +/- 0.048 versus 0.189 +/- 0.045, p = 0.002; D0: 189.6 +/- 26.3 cGy versus 108.7 +/- 18.2 cGy, p = 0.047) and CD3+ cases had smaller alpha values than CD3- cases (0.454 +/- 0.087 versus 0.765 +/- 0.152, p = 0.06). Thus, clonogenic cells from CD3+ T-lineage ALL/NHL patients were more resistant to radiation than clonogenic cells from CD3- T-lineage ALL/NHL patients. In the clinical arm of our study, 33 T-lineage ALL/NHL patients received autologous bone marrow transplants during remission. Pretransplant conditioning consisted of total body irradiation combined with high dose chemotherapy. The expression of CD3 antigen predicted the outcome of relapsed T-lineage ALL/NHL patients undergoing autologous bone marrow transplantation following total body irradiation plus high dose chemotherapy. Overall, the Kaplan-Meier estimate and standard error of the probability of remaining in remission at 3.5 years was 11 +/- 9% with a median relapse-free interval of 102 days. The disease-free survival at 3.5 years was 8 +/- 7% with a median disease-free survival time of 96 days. Notably, the expression of CD3 antigen on T-lineage ALL/NHL cells correlated with the probability of relapse after bone marrow transplantation. While 16 of 19 CD3+ patients relapsed after bone marrow transplantation, only 3 of 8 CD3- patients relapsed. The Kaplan-Meier estimates and standard errors of the probability of remaining in remission at 1 year after bone marrow transplantation were 7 +/- 6% (median relapse-free interval = 74 days) for CD3+ patients (n = 19) and 63 +/- 17% for CD3- patients (n = 8) (p = 0.006).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1429096 TI - Differential radioprotection of cultured human diploid fibroblasts and fibrosarcoma cells by WR1065. AB - The present studies were performed to determine whether WR1065, the dephosphorylated, free-thiol active metabolite of WR2721, could provide differential radioprotection of normal and tumor cell lines in vitro and secondly to investigate potential mechanisms for the selective nature of the radioprotection at the cellular and molecular level. When 4 mM WR1065 was administered 30 min prior to and during irradiation, a protection factor of 1.9 was obtained in clonogenic assays performed with normal human diploid fibroblasts (AG1522) while no protection of fibrosarcoma cells (HT1080) was observed. Some radioprotection of fibrosarcoma cells was observed with higher drug concentrations (10-40 mM), but the increase in survival was considerably less than the plateau level reached with the diploid fibroblasts (3-fold vs 24-fold at 6 Gy). The observation of such a selective effect in vitro with WR1065 indicates that differences in tissue-specific variables such as blood flow, pH, pO2, and drug dephosphorylation cannot solely account for the selective nature of the radioprotection afforded by WR2721 in vivo. Incubation of nucleoids with increasing concentrations of the DNA intercalating dye propidium iodide was used to titrate the ability of DNA to undergo supercoiling changes. The relaxation and rewinding of supercoiled DNA loops in isolated nucleoids serves as an indicator of both the presence of DNA damage and inherent differences in DNA loop characteristics. Fibrosarcoma cells had a much larger propidium iodide-relaxable DNA loop size than fibroblasts. The rewinding phase of the DNA supercoiling response is impaired by the presence of radiation-induced DNA strand breaks. Four mM WR1065 resulted in a significant reduction in the amount of rewinding inhibition observed after a dose of 10 Gy in diploid fibroblasts (protection factor = 1.43) but did not alter the response of irradiated fibrosarcoma cells. These results, indicating that WR1065 had a preferential radioprotective effect in vitro on both survival and the manifestation of DNA damage at the nucleoid level, are consistent with the hypothesis that cell type differences in chromatin organization and DNA-drug associations could play a role in the selective radioprotection. PMID- 1429097 TI - Intraoperative and external radiotherapy in resected gastric cancer: updated report of a phase II trial. AB - From September 1984 to August 1991, 48 evaluable patients with resected gastric cancer and apparent disease confined to locoregional area were treated with intraoperative electron beam boost to the celiac axis and peripancreatic nodal areas (15 Gy) and external irradiation (40 to 46 Gy in 4 to 5 weeks) including the gastric bed and upper abdominal nodal draining regions. At the time of evaluation for IORT, the disease was primary in 38 cases, recurrent but resectable in four (anastomosis), and unresectable in four (nodal). Post operative complications were reversible. Acute tolerance to the complete treatment program was acceptable. Late complications included life-threatening events: Six episodes of gastro intestinal bleeding (three of them had an arteriographic documentation of arterioenteric fistula) and nine with severe enteritis (five required reoperation). Other long-term treatment related complications were six cases of vertebral collapse. The median follow-up time for the entire group is 22 months. Locoregional recurrence/persistence of disease has been identified in five patients (three with residual and/or recurrent postsurgical tumor). Systemic tumor progression has been detected in 15 patients (11 in intra-abdominal sites). Overall actuarial survival for patients with positive or negative serosal involvement was 33% versus 56%. It is concluded that the treatment program described is able to induce a high locoregional tumor control rate (100%) when used strictly in an adjuvant setting and might control long term, a small portion of patients not amenable for curative surgery (2 out of 8 patients with confirmed residual post-surgical disease). Gastrointestinal bleeding and enteritis are findings that indicate treatment intensity at the upper limits of tissue tolerance. Assessment of long term tolerance of pancreatic parenchyma and large blood vessels (tissues included in the IRORT field) are pending for longer follow-up and the appropriate selective studies. PMID- 1429098 TI - The frequency of translocations after treatment for Hodgkin's disease. AB - We studied the frequency of translocations in peripheral blood lymphocytes of patients with Hodgkin's disease to determine the extent of chromosome changes induced by radiation or radiation and chemotherapy. Comparisons were made to patients with second cancers to determine if this population is more susceptible to the effects of treatment. Group one included six patients with newly diagnosed Hodgkin's disease who were treated with radiation only. Group two included Hodgkin's disease patients who were treated 12-24 years previously and have been continuously free of disease. Five of these patients were treated with radiation only and five patients received radiation and mechlorethaminehydrochloride, oncovin, procarbazine, prednisone (MOPP) chemotherapy for six cycles. Group three included three patients who developed a second cancer after successful treatment for Hodgkin's disease. Two of these patients had a sarcoma within the radiation field and one had breast cancer. Metaphase spreads were obtained from cultured lymphocytes and hybridized with a chromosome 4 specific probe. After fluorescein staining, approximately 1000 metaphases were scored per patient. In group one only one patient in six demonstrated translocations in chromosome 4 before treatment for a mean frequency of .0009. After treatment the frequency of translocations increased to a mean of .016 (p = .036) (range .006-.034). Group two patients treated with radiation only had a mean translocation frequency of .012 (range .004-.022) in comparison to the radiation/mechlorethaminehydrochloride, oncovin, procarbazine, prednisone chemotherapy treated patients who demonstrated a mean frequency of .016 (p = .425) (range .0009-.023). The third group of second cancer patients showed inconsistent translocation frequencies of .002, .020, and .035. Of these patients, the one who demonstrated the greatest frequency of translocations (.035) was treated with mechlorethaminehydrochloride, oncovin, procarbazine, prednisone/adriamycin, bleomycin, vinblastine, decadron) and radiation. Our data demonstrates a statistically significant increase in translocations detected after radiation. When compared to combined modality therapy a greater mean frequency of translocations is observed over radiation alone; however, this was not statistically significant. In the three patients who developed second cancers in our series we saw no consistent increase in translocation frequency compared to Hodgkin's disease patients who did not develop a second cancer. PMID- 1429099 TI - Adjuvant radiotherapy in high stage transitional cell carcinoma of the renal pelvis and ureter. AB - This review was undertaken to assess the influence of adjuvant radiation therapy on failure patterns and survival in high stage transitional cell carcinoma of the renal pelvis or ureter. Ninety-four patients with transitional cell carcinoma of the renal pelvis or ureter were retrospectively reviewed. Twenty-six had American Joint Commission stage T3 or T4 N0/+, M0 disease and underwent curative resections (median follow-up 13.5 months, range 3-311). Local failure was defined as recurrence in the tumor bed, regional nodes, or ureteral stump. Time to recurrence and survival were calculated from the time of pathologic diagnosis. Variables associated with local failure, distant metastasis, and survival were analyzed using univariate and multivariate analysis. Seventeen received surgery only, nine received adjuvant radiation therapy (median dose 50 Gy). Local failure occurred in 9 of 17 without and 1 of 9 with adjuvant radiation therapy (p = 0.07). Actuarial 5-year local control was 34% without and 88% with adjuvant radiation therapy. Cox step-wise regression confirmed adjuvant radiation therapy (p = 0.006) and grade (p = 0.006) as significantly associated with local failure. No patients with low grade lesions suffered local failure either with or without adjuvant radiation therapy. High grade lesions had an local failure rate of 15% with and 71% without adjuvant radiation therapy. Metastatic disease occurred in 4 of 9 and 8 of 17 with and without radiation therapy. No significant factors influencing distant failure were identified. Five-year actuarial survival was 44% with and 24% without adjuvant radiation therapy. The survival differences were not statistically significant on univariate or multivariate analysis. High staged transitional cell carcinoma of the renal pelvis or ureter has a substantial local failure risk after surgery alone. Adjuvant radiation therapy markedly reduces this risk but has no impact on distant disease which occurs in approximately 50%. Effective adjuvant therapy will require effective systemic therapy in addition to adjuvant radiation therapy. PMID- 1429100 TI - The importance of brachytherapy technique in the management of primary carcinoma of the vagina. AB - This retrospective analysis of 49 cases of primary carcinoma of the vagina treated with radiation therapy alone from 1970-1988 examines the results of treatment with an emphasis on the importance of brachytherapy technique. Thirty six patients were treated with combined external beam radiation and brachytherapy, 11 patients were treated with external beam alone, and two patients were treated with brachytherapy alone. Brachytherapy techniques used included intracavitary implants, temporary Ir-192 interstitial implants, and permanent I-125 interstitial implants. Intracavitary therapy included the use of a fractionated high dose rate intravaginal cylinder, tandem and ovoids, and a low dose rate intravaginal cylinder. The 5-year actuarial survival was 44% for Stage I (six patients), 48% for Stage II (27 patients), 40% for Stage III (10 patients), and 0% for Stage IVa and IVb (six patients). There was a significant increase in the 5-year actuarial survival for those patients who had brachytherapy as part of their treatment compared to those patients treated with external beam alone (50% vs. 9%) (p < .001). For Stages II and III, there was a trend toward improved actuarial and crude disease free survival with the use of a temporary Ir-192 interstitial implant as part of the treatment compared to the use of intracavitary brachytherapy as part of the treatment (80% vs. 45%) (p = 0.25) and (75% vs. 44%) (p = 0.08), respectively. Brachytherapy plays an important role in the management of primary vaginal cancer. A temporary interstitial implant should be used over an intracavitary form of therapy for more invasive disease. PMID- 1429102 TI - Hypofractionated accelerated radiotherapy in osteogenic sarcoma. AB - A method of hypofractionated accelerated radiotherapy (3 weekly fractions of 6 Gy over 2 weeks to a total tumor dose of 36 Gy) was used as single modality in 14 patients with osteogenic sarcoma for palliative treatment of the primary tumor site (six cases) or skeletal metastases (15 sites). A durable response, radiologically assessed, was obtained in 17 of the 21 (81%) irradiated sites. When this irradiation modality was combined with chemotherapy, to treat patients presenting with synchronous metastases (eight cases) or refusing amputation (five cases), a radiologically assessed response was observed in 12 of 13 (92%). In no case did a local recurrence occur before surgery or death because of progressive disease elsewhere. Of the seven patients who later had to undergo ablative surgery, a 100% and 95% tumor necrosis was observed in 6 and 1, respectively. Because of intralesional resection of primary osteogenic sarcoma after preoperative chemotherapy, seven additional patients were irradiated. None recurred at the level of the primary site. Although effective in inducing remission of osteogenic sarcoma, this irradiation method produced severe damages to normal tissues in a high proportion of patients. PMID- 1429101 TI - Preliminary results in heavy charged particle irradiation of bone sarcoma. AB - Between 1979 and 1989, 17 patients with unfavorable bone sarcoma were treated wholly or in part with heavy charged particle irradiation (helium and/or neon ions) at the University of California Lawrence Berkeley Laboratory. The majority of tumors were located near critical structures such as the spinal cord or brain. Gross tumor was present in all but two patients at the time of irradiation. Six patients were treated for recurrent disease. Histologies included osteosarcoma, Ewing's sarcoma, and recurrent osteoblastoma. Four of the osteosarcomata were believed to have been induced by previous therapeutic irradiation for various tumors. Follow-up time since initiation of radiation ranged from 7 to 118 months (median 40 months). The 5-year Kaplan-Maier local control rate was 48%; the corresponding survival rate was 41%. Over half the patients succumbed to distant metastases despite the majority of patients receiving chemotherapy. In this preliminary study, we have shown that heavy charged particle irradiation can be effectively used for control of bone sarcoma. A Phase II trial is warranted to determine optimal treatment for unresectable or gross residual disease. PMID- 1429103 TI - The clinical utility of magnetic resonance imaging in 3-dimensional treatment planning of brain neoplasms. AB - Results of the clinical experience gained since 1986 in the treatment planning of patients with brain neoplasms through integration of magnetic resonance imaging (MRI) into computerized tomography (CT)-based, three-dimensional treatment planning are presented. Data from MRI can now be fully registered with CT data using appropriate three-dimensional coordinate transformations allowing: (a) display of MRI defined structures on CT images; (b) treatment planning of composite CT-MRI volumes; (c) dose display on either CT or MRI images. Treatment planning with non-coplanar beam arrangements is also facilitated by MRI because of direct acquisition of information in multiple, orthogonal planes. The advantages of this integration of information are especially evident in certain situations, for example, low grade astrocytomas with indistinct CT margins, tumors with margins obscured by bone artifact on CT scan. Target definitions have repeatedly been altered based on MRI detected abnormalities not visualized on CT scans. Regions of gadolinium enhancement on MRI T1-weighted scans can be compared to the contrast-enhancing CT tumor volumes, while abnormalities detected on MRI T2-weighted scans are the counterpart of CT-defined edema. Generally, MRI markedly increased the apparent macroscopic tumor volume from that seen on contrast-CT alone. However, CT tumor information was also necessary as it defined abnormalities not always perceptible with MRI (on average, 19% of composite CT MRI volume seen on CT only). In all, the integration of MRI data with CT information has been found to be practical, and often necessary, for the three dimensional treatment of brain neoplasms. PMID- 1429104 TI - Radiosurgery target point alignment errors detected with portal film verification. AB - Stereotactic radiosurgery with a linear accelerator requires an accurate match of the therapeutic radiation distribution to the localized target volume. Techniques for localization of the target volume using CT scans and/or angiograms have been described. Alignment of the therapeutic radiation distribution to the intended point in stereotactic space is usually accomplished using precision mechanical scales which attach to the head ring. The present work describes a technique used to verify that the stereotactic coordinates of the center of the intended radiation distribution are in agreement with the localized target point coordinates. This technique uses anterior/posterior and lateral accelerator portal verification films to localize the stereotactic coordinates of the center of the radiation distribution with the patient in the treatment position. The results of 26 cases have been analyzed. Alignment errors of the therapeutic radiation distribution in excess of 1 mm have been found using the portal film verification procedure. PMID- 1429105 TI - Computer systems and mechanical tools for stereotactically guided conformation therapy with linear accelerators. AB - An integrated system for fractionated, stereotactically guided conformation radiotherapy has been developed. The system components are a stereotactic fixation system that can be used each treatment day, a localization, and positioning unit that can be used during x-ray computer tomography, magnetic resonance imaging, positron emission tomography, and radiographical examinations as well as for treatment. Conformal precision radiotherapy is planned with a new three-dimensional treatment planning system (Voxel-Plan-Heidelberg) which comprises, among others options, a three-dimensional image correlation procedure as well as routines for the calculation of coplanar and non-coplanar irradiations with irregularly shaped fields. Two different multi-leaf collimators have been designed for precision radiotherapy in the head and neck region. A manual multi leaf collimator is used for irradiations with stationary beams or for moving beam treatments with invariable irregularly shaped fields. This collimator system is now being used for patient treatments. The design of a computer controlled multi leaf collimator unit for multiple fixed field irradiation techniques is discussed. All system components are aimed at conforming dose distributions for fractionated radiotherapy treatments to the target to improve sparing of adjacent normal tissues, and at achieving a sufficient geometrical accuracy in the dose application. PMID- 1429106 TI - Three-dimensional dose distribution of total body irradiation by a dual source total body irradiator. AB - This study describes the three-dimensional dosimetric characteristics of total body irradiation by our dedicated irradiation unit, which consists of two modified 4-MV linear accelerators mounted opposite each other, providing a field size of 220 cm x 80 cm at the midplane. Our dose calculation algorithm considers the three-dimensional contour of the patient to evaluate the primary and scatter doses. The data base for the calculation includes tissue-to-maximum ratios measured for the large fields. The lung dose correction was calculated using the methods of Batho or ratio of TMR. The accuracy of the calculated dose distributions was verified by measurements with ionization chambers in a humanoid phantom. We also describe and verified a technique to achieve desirable midline lung doses using lead shields. The flexibility and the accuracy of the planning system offers the potential in optimizing the therapeutic ratio for total body treatments. PMID- 1429107 TI - Dose determination in high dose-rate brachytherapy. AB - Although high dose-rate brachytherapy with a single, rapidly moving radiation source is becoming a common treatment modality, a suitable formalism for determination of the dose delivered by a moving radiation source has not yet been developed. At present, brachytherapy software simulates high dose-rate treatments using only a series of stationary sources, and consequently fails to account for the dose component delivered while the source is in motion. We now describe a practical model for determination of the true, total dose administered. The algorithm calculates both the dose delivered while the source is in motion within and outside of the implanted volume (dynamic component), and the dose delivered while the source is stationary at a series of fixed dwell points. It is shown that the dynamic dose element cannot be ignored because it always increases the dose at the prescription points and, in addition, distorts the dose distribution within and outside of the irradiated volume. Failure to account for the dynamic dose component results in dosimetric errors that range from significant (> 10%) to negligible (< 1%), depending on the prescribed dose, source activity, and source speed as defined by the implant geometry. PMID- 1429108 TI - Hyperthermia and brachytherapy for glioma--will cooler heads prevail? PMID- 1429109 TI - Block mounting solvents. PMID- 1429110 TI - External radiation therapy versus prostatectomy. PMID- 1429111 TI - Oxygen enhancement ratio of a murine fibrosarcoma. PMID- 1429112 TI - Uneasy rests the head that wears the template. PMID- 1429113 TI - Cultural factors in the darker passions. PMID- 1429115 TI - On falling in love and creativity. AB - This paper discusses the ego functioning and self psychological aspects of falling in love and passionate love. These universal and extraordinary phenomena are conceptualized as representing the activity of the creative imagination in solving problems related to coping with intense narcissistic and libidinal pressures. The work of other authors is reviewed and recast into a metapsychological framework involving ego and superego contributions to the experience, and focused on self cohesion. An illustrative clinical psychotherapy case is presented in an effort to understand what has traditionally appeared to be a mysterious and disjunctive life experience, and to explore the creative surge that can be generated by falling in love both in and out of the transference. PMID- 1429114 TI - Correlation of brain activity with emotion: a basis for developing treatment of violent-aggressive behavior. PMID- 1429116 TI - A reassessment of Little Hans, his parents, and his castration complex. PMID- 1429117 TI - Psychoanalysis as a "normal" science. PMID- 1429118 TI - The psychoanalyst's experience on intimacy with the patient. PMID- 1429119 TI - German voices about the Nazi terror: late opponents and postwar critics. AB - Of the dark passions that afflict mankind none has surpassed Nazism in its dimensions of evil. Descriptions of its terror abound, and many attempts have been made to understand what it was that drove an entire nation to serve an ideology of evil and madness. Many volumes have been written about the historical background of what occurred and about the socioeconomic factors that contributed to the rise of Nazism. Attempts have also been made to build psychodynamic underpinnings, so as to help us understand the inconceivable. I believe that we will never grasp it fully, yet there are sources that have remained underutilized, particularly on our side of the Atlantic. I am referring to books written by German authors. Some of them exist in English translation, most do not. For years I have read everything on the subject that came to my attention. I have been shaped by those events and cannot let go of them. So here is an occasion to share some of my thoughts with you. PMID- 1429120 TI - Oedipal ties and the issue of separation-individuation in traditional Confucian societies. PMID- 1429122 TI - Examining veterinarians for physical and mental fitness. PMID- 1429121 TI - Psychoanalysis, the Hispanic poor, and the disadvantaged: application and conceptualization. PMID- 1429124 TI - Comparison of the human and canine Schiotz tonometry conversion tables in clinically normal cats. AB - Intraocular pressure (IOP) was measured in 73 eyes of 37 clinically normal cats with 2 applanation tonometers (Tono-Pen and Mackay-Marg) and the Schiotz indentation tonometer, using the 5.5- and 7.5-g weights. Statistically, the Tono Pen tonometer underestimated IOP compared with the values obtained by use of the Mackay-Marg tonometer (P less than 0.0001) and the Schiotz tonometer, with either weight and either the human (P less than 0.01) or the canine (P less than 0.0001) calibration tables. Estimates of IOP using the human calibration table and either the 5.5- or 7.5-g weight were not significantly different from each other or from those obtained with the Mackay-Marg tonometer. Schiotz measurements obtained with either weight and converted using the canine calibration table were not only significantly (P less than 0.0001) different from each other, but were also clinically and significantly (P less than 0.0001) higher than measurements obtained with the Tono-Pen and Mackay-Marg tonometers or the Schiotz tonometer, using the human calibration table and either weight. Approximately three quarters of clinically normal cats had an IOP greater than or equal to 30 mm of Hg when Schiotz tonometer measurements were converted with the canine conversion table. The human calibration table was the most clinically useful table for converting Schiotz measurements from clinically normal feline eyes to estimates of IOP in mm of Hg. Normal mean (+/- SD) feline readings with the Schiotz tonometer and the 5.5-g weight was 3.9 +/- 1.4 tonometer scale units (range, 1.0 to 7.5; 95% confidence interval [CI], 1.1 to 6.7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429123 TI - Enzyme-linked immunosorbent assays for the detection of Toxoplasma gondii specific antibodies and antigens in the aqueous humor of cats. AB - Serum and aqueous humor samples, collected from 14 clinically normal cats and 96 cats with clinical evidence of intraocular inflammation, were assayed with ELISA for Toxoplasma gondii-specific immunoglobulin M (IgM), T gondii-specific IgG, T gondii-specific antigens, total IgG, and total IgM. Additionally, serum was assayed with ELISA for feline leukemia virus p27 antigen and antibodies against the feline immunodeficiency virus as well as with an immunofluorescent antibody assay for antibodies against feline coronaviruses. Calculation of the Goldmann Witmer coefficient (C-value) for the T gondii-specific antibodies detected in aqueous humor established the likelihood of local antibody production. Serologic evidence of present or prior infection by an infectious agent was found in 81.9% of the clinically affected cats from which serologic results were available (77/94 cats). Seropositive results for toxoplasmosis were found in 74.0% of the clinically affected cats. Anterior segment inflammation was found in 93.1% (81/87 cats from which information was available) of the clinically affected cats, most of which were older males. Toxoplasma gondii-specific antibodies were not detected in the aqueous humor of 6 seropositive, clinically normal cats. The C values for aqueous T gondii antibodies were greater than 1 in 44.8% of the cats and greater than 8 in 24.0% of the cats. Response to treatment with clindamycin HCl was positive in 15/20 (75%) of the T gondii-seropositive, clinically affected cats treated with this drug. In 13/15 (86.7%) T gondii-seropositive, clinically affected cats having a C-value greater than 1, response to treatment with clindamycin HCl was positive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429125 TI - Comparison of the human and canine Schiotz tonometry conversion tables in clinically normal dogs. AB - Intraocular pressure (IOP) was measured in 114 eyes of 57 clinically normal dogs with 2 applanation tonometers (Tono-Pen and Mackay-Marg) and the Schiotz indentation tonometer, using the 5.5- and 7.5-g weights. Significant differences were not detected between measurements obtained with the Tono-Pen and Mackay-Marg tonometers the Mackay-Marg and Schiotz tonometers using either weight and conversion with the human calibration table, or the Tono-Pen and Schiotz tonometers using the 7.5-g weight and the human calibration table. Values obtained by use of the Tono-Pen tonometer were significantly less (P less than 0.005) than values obtained with the Schiotz tonometer when a 5.5-g weight and the human calibration table were used, but the amount was clinically unimportant. Estimates of IOP using the Schiotz tonometer and the canine calibration table, and either the 5.5- or 7.5-g weight were clinically and significantly much higher (P less than 0.0001) than estimates obtained with the Tono-Pen, Mackay-Marg, or Schiotz tonometers, using the human calibration table and either weight. Sixty to 70% of clinically normal dogs had an IOP greater than or equal to 30 mm of Hg when Schiotz scale measurements were converted with the canine conversion table. For clinically normal dogs, the human calibration table was the most clinically useful table for converting Schiotz tonometer measurements to mm of Hg. Normal mean (+/- SD) canine readings with the Schiotz tonometer and the 5.5-g weight was 4.9 +/- 1.5 tonometer scale units (range, 2 to 11; 95% confidence interval, 1.9 to 7.9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429126 TI - Effects of electrolyte solutions for oral administration on clotting of milk. AB - The effect of electrolyte solutions commercially formulated for oral administration on clotting of milk was investigated in vitro. Rennet or abomasal fluid was used as the clotting agent. Electrolyte solutions that contained large amounts of bicarbonate or citrate (greater than 40 mEq/L) had marked adverse effects on milk clotting, probably because bicarbonate increased pH and because citrate chelated calcium. Addition of solutions that did not contain alkalinizing agents resulted in normal or enhanced clotting, and enhancement was associated with the presence of acid phosphate salts. Electrolyte solutions that included acetate as the alkalinizing agent did not interfere with milk clotting as long as pH of the final solution was acidic and minimal amounts of citric acid salts were present (less than 10 mEq/L). Acetate-containing electrolyte solutions can be used for oral administration in calves in which alkalinization of blood without interference with milk clotting is desired. PMID- 1429127 TI - Seroprevalence of antibodies to Borrelia burgdorferi in a population of horses in central Texas. AB - Four hundred sixty-nine serum samples were obtained from horses admitted to the internal medicine service of the Texas Veterinary Medical Center between Jan 1 and Dec 31, 1990. Serum samples were tested by ELISA for antibody to Borrelia burgdorferi. Of these 469 samples, 1 (0.2%) was repeatedly seropositive for the organism by ELISA. Confirmatory testing by protein immunoblot was negative. The observed seroprevalence was 0%; the upper bound of the 95% confidence interval was 0.6%. These findings indicate the evidence of infection with B burgdorferi is presently uncommon in horses in central Texas. PMID- 1429128 TI - Removal of nasogastric tube fragments from three horses. AB - Three horses were admitted for retrieval of polyurethane nasogastric tube fragments. The fragments were removed from the esophagus or stomach of 2 horses by manipulation of a snare introduced through the biopsy port of an endoscope. The fragments were surgically removed from the stomach of the third horse. PMID- 1429130 TI - Conservative management of fourth tarsal bone fracture in a draft horse. AB - A fourth tarsal bone fracture was treated conservatively in an adult draft horse. Seven months after the injury, the horse had no evidence of lameness and was able to compete in athletic events. It has been suggested that conservative management of these fractures be considered for brood animals or animals used for less strenuous activities. The outcome of this case suggests that fourth tarsal bone fractures can be successfully treated in athletic animals with conservative management. PMID- 1429129 TI - Postsurgical ventricular tachycardia in a horse. AB - A 2-year-old Thoroughbred racehorse developed ventricular tachycardia after elective laryngoplasty and ventriculectomy were performed while anesthesia was maintained with halothane. During surgery, the horse became febrile and developed transient mild hypercarbia. The horse was treated with an IV infusion of quinidine gluconate. Continuous electrocardiographic monitoring was used to evaluate cardiac rhythm during treatment, and conversion was achieved after 12 hours of IV infusion. The inciting cause for the arrhythmia was not determined. PMID- 1429131 TI - Ovarian mass in three mares with regular estrous cycles. AB - Three mares with regular estrous cycles and a large ovary were examined. In each case, the ovary was composed of a single, fluid-filled cavity with a thick capsule. The ovarian mass was surgically removed from each mare. Histologic diagnosis of each mass was different. PMID- 1429132 TI - Correction of cervical esophageal stricture in a dog by creation of a traction diverticulum. AB - A cervical esophageal stricture was corrected in a dog by creation of a traction diverticulum. Although abnormal esophageal motility persisted in the portion of the esophagus cranial to the stricture, the clinical effects of the stricture were ameliorated by the simple surgical procedure. PMID- 1429133 TI - Multiple cardiac anomalies in a cat. AB - A 7-week-old domestic shorthair cat was examined because of congestive heart failure. Echocardiography and angiography were used to identify multiple cardiac anomalies. Because of the uncorrectable nature of the defects, the cat was euthanatized. Necropsy revealed persistent left vena cava, patent foramen ovale, and a right atrial/left ventricular canal. The right atrioventricular valve was replaced by a small ostium, and no chordae tendinae or papillary muscles were observed around the ostium. The pulmonary trunk originated from the right atrium. The right ventricular free wall was approximately 1 mm thick. PMID- 1429135 TI - Subconjunctival cyst associated with Thelazia gulosa in a calf. AB - A large subconjunctival cyst of 4 weeks' duration was surgically excised from the left eye of a 7-month-old Simmental calf. Two white, partially mineralized, approximately 1-cm-long, fertile female nematodes subsequently identified as Thelazia gulosa were found embedded in the cyst wall. Thelazia spp are generally regarded as nonpathogenic or mildly pathogenic in cattle in North America, despite reported infection rates ranging from 12.2 to 34.2%. Additionally, parasitic subconjunctival nodules associated with Thelazia spp rarely have been reported in the past, and cyst formation has not been described. It was postulated that in this calf, immature or adult worms may have penetrated normal tissue barriers, or entered via an earlier conjunctival wound, and created an inflammatory response with subsequent cyst formation. PMID- 1429134 TI - Use of autogenous cancellous bone graft for treatment of osteolytic defects in the phalanges of three cattle. AB - Osteolytic defects were detected radiographically in the distal sesamoid bone of a 16-month-old Bralers heifer, in the middle phalanx of a 14-month-old American Gray Brahman bull, and in the distal phalanx of a 3-year-old American Gray Brahman bull. The articular cartilage was damaged in each animal because of osteolysis or pathologic fracture. After each animal was anesthetized and positioned in lateral recumbency, the lesions were curetted and packed with cancellous bone harvested from the same animal's tuber coxae. Basic postoperative management involved stall rest and immobilization of the graft site with a fiberglass cast (42 to 79 days), after which a support bandage was used for approximately 2 weeks. Recurrence of lameness has not been observed in these animals for 60 months, 58 months, and 21 months, respectively. These cases exemplify the benefit of using an autogenous cancellous bone graft for treatment of severe osteolysis of a digit in cattle. PMID- 1429136 TI - Prepurchase evaluation of horses: 134 cases (1988-1990). AB - To quantify some components of prepurchase evaluations in horses, records from 134 evaluations performed during a 2-year period were reviewed and the outcome was determined via telephone follow-up interview. Sixty-two percent of the prepurchase evaluations had been performed at the clinic and 38% had been performed in the field by the ambulatory service. All evaluations included physical and lameness examinations, whereas radiography (49%), endoscopy (15%), nerve blocking (5%), transrectal palpation (3%), hematologic analysis (2%), electrocardiography (2%), drug testing for analgesic agents (2%), and ultrasonography of the flexor tendons (1%) were not always performed. Fifty-nine percent of horses evaluated at the clinic were radiographed, compared with 33% of horses evaluated in the field (P less than 0.05). Thirty-seven percent of horses evaluated were judged serviceable for their intended use. Thirty-five percent of horses evaluated at the clinic were assessed to be serviceable, compared with 41% of those evaluated in the field (P less than 0.05). Horses used for pleasure riding (48%) tended to be considered serviceable more often than horses used for more athletic endeavors (3-day eventing, 33%; hunter/jumper, 24%; show, 31%; dressage, 30%). The most common basis for finding a horse unserviceable was lameness (88%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429137 TI - Tarsal lameness of dairy bulls housed at two artificial insemination centers: 24 cases (1975-1987). AB - Degenerative joint disease of the tarsi was diagnosed in 20 of 24 Holstein bulls with tarsal lameness at 2 artificial insemination centers from 1975 to 1987. Each of the 2 centers housed about 100 bulls/yr. Of the 24 bulls with tarsal lameness, 22 were from the artificial insemination center designated as A, and 2 were from the center designated as B. Examination of the housing and management procedures revealed that center A had concrete floors with cuboidal-shaped yards, whereas center B had deep sand flooring, with long, narrow yards. The only other difference between the 2 centers was that center A used 1- and 2-year-old bulls as teasers for older, heavier bulls to mount, whereas center B used bulls that were at least 6 years old to withstand the stress placed on their hind limbs by the weight of bulls undergoing semen collection. Radiographic lesions of tarsi of bulls from both centers ranged from distention of the tibiotarsal joint pouch to hypertrophic degenerative osteoarthritis of the distal, intertarsal, and tarsometatarsal joints. It was concluded that the concrete flooring and the semen collecting practices were responsible for the high prevalence of tarsal lameness and degenerative joint disease of the tarsi in bulls housed at center A. PMID- 1429138 TI - Immunodeficiency syndrome associated with wasting and opportunistic infection in juvenile llamas: 12 cases (1988-1990). AB - Immunodeficiency was diagnosed as the cause of severe debilitating disease characterized by weight loss, failure to grow, and persistent infections that failed to respond to treatment in 12 young llamas. The llamas were affected after maternal-acquired immunity had decreased; failure of passive transfer of immunoglobulins thus was not suspected. Areas of lymph nodes containing T lymphocytes were hypocellular, suggesting T-cell involvement. High serum immunoglobulin concentrations were not found, despite the existence of infectious disease, suggesting at least secondary B-cell involvement. Results of lymphocyte blastogenesis assays were suggestive of B- and T-cell involvement. It was not possible to determine whether the condition was inherited or acquired. PMID- 1429139 TI - Leiomyosarcoma in dogs: 44 cases (1983-1988). AB - During a 5-year period, leiomyosarcoma was diagnosed in 57 dogs. Forty-four dogs were included in the study on the basis of completeness of medical records. All dogs underwent exploratory laparotomy, and dogs were allotted to 4 groups according to primary site of tumor: spleen (16 dogs, median age 10.3 years), stomach/small intestine (13 dogs, median age 10.3 years), cecum (10 dogs, median age 11.8 years), and liver (5 dogs, median age 9 years). All dogs with leiomyosarcoma of the liver had visible metastasis and were euthanatized at surgery. In the other 3 groups, 79% of the dogs had no gross evidence of metastasis at surgery, and 64% survived greater than 2 weeks. Median survival in these 3 groups was 10 months (range, 1 month to 7 years); 48% died of metastasis, 32% died of unrelated causes, and 16% died of unknown causes. The prognosis in dogs with leiomyosarcoma of the spleen, stomach, small intestine, and especially the cecum is good to excellent if surgery is performed. In dogs with leiomyosarcoma of the liver, the prognosis is poor. PMID- 1429140 TI - Orbital neoplasms in cats: 21 cases (1974-1990). AB - Squamous cell carcinoma was the most common neoplasm found in a review of case records of 21 cats with histopathologically confirmed orbital neoplasms. Other neoplasms found were lymphosarcoma, undifferentiated carcinoma, malignant melanoma, adenocarcinoma, fibrosarcoma, chondroma, and hemangiosarcoma. Three (14%) neoplasms were primary, 15 (71%) were secondary, invading the orbit from adjacent tissues, and 3 (14%) were a manifestation of multicentric disease. The most common clinical sign was exophthalmia, followed by chronic epiphora, enophthalmia, and strabismus. Mean survival time after diagnosis was 1.9 months. Ten cats were euthanatized at the time of diagnosis because of extensive disease. Mean survival time of the other 11 cats was 4.3 months. Skull radiography was helpful in diagnosing orbital neoplasms in 8 of 11 cats that had invasion of the orbit by adjacent neoplasms. PMID- 1429141 TI - Pupilloplasty in a great horned owl with pupillary occlusion and cataracts. PMID- 1429142 TI - Femoral artery pseudoaneurysm in a monkey. AB - Pseudoaneurysm formation as a complication of routine blood collection was diagnosed in a monkey. Damage to the femoral artery resulted in hematoma formation with secondary organization, encapsulation, and vascular communication. Progressive lameness and muscular atrophy were the primary clinical signs. Surgical correction of the artery defect helped resolve the monkey's lameness and muscle atrophy. PMID- 1429144 TI - Stalking a killer: the "disease" of euthanasia. PMID- 1429143 TI - What is your diagnosis? Circumscribed metallic foreign body in the pelvic canal. PMID- 1429145 TI - APHIS biologics personnel hear from constituents, consumers. PMID- 1429146 TI - Veterinary service market for companion animals, 1992. Part I: Companion animal ownership and demographics. PMID- 1429147 TI - ECG of the month. PMID- 1429148 TI - "My first love is heavy horses ...". PMID- 1429149 TI - Impaired veterinarians need and deserve our help and understanding. PMID- 1429150 TI - Questions radiographic interpretation. PMID- 1429151 TI - Corticoid:creatinine ratio. PMID- 1429153 TI - Self-directed continuing education. PMID- 1429152 TI - Veterinary service market for companion animals, 1992. Part II: Veterinary service use and expenditures. PMID- 1429154 TI - Four essential components of veterinary education for the 21st century. PMID- 1429155 TI - The perils of perfectionism. PMID- 1429156 TI - Comparison of lidocaine, xylazine, and xylazine/lidocaine for caudal epidural analgesia in horses. AB - Caudal epidural analgesia was achieved in 6 adult horses on 3 successive occasions at weekly intervals by injection of lidocaine, xylazine, and a combination of lidocaine/xylazine through indwelling epidural catheters. Analgesia was defined as a lack of response to pinprick and hemostat pressure in the skin of the perineal area. A significant (P < 0.05) difference was not found for time of onset of analgesia between lidocaine (4.3 +/- 0.8 minutes, mean +/- SEM) and the lidocaine/xylazine combination (5.3 +/- 1.3 minutes). Time to onset of analgesia after administration of xylazine was significantly (P < 0.05) longer (32.0 +/- 3.4 minutes) than that for either of the other 2 treatments. Duration of analgesia was significantly (P < 0.05) longer for the combination (329.8 +/- 6.2 minutes) than for either drug used alone (lidocaine, 87.2 +/- 7.5 minutes; xylazine, 204.2 +/- 12.9 minutes). Pulse and respiratory rates were not significantly altered by any of the drugs. Neurologic sequelae were not clinically apparent after administration of the drugs or after chronic epidural catheterization. PMID- 1429157 TI - Microvascular permeability changes in ischemia/reperfusion injury in the ascending colon of horses. AB - The normal microvascular permeability of the ascending colon in horses and the microvascular permeability of that segment after ischemia and reperfusion were investigated. Microvascular permeability was estimated by the ratio of lymphatic protein to plasma protein concentration (Cl/Cp) at high lymph flow rates in 8 adult horses in 2 equal groups: normal and ischemic (2-hour period). Lymphatic flow rates and lymph and plasma protein concentrations were determined. Intestinal biopsy specimens were obtained at the end of each experiment. Flow independent values were selected and compared by one-way ANOVA, and the mean and SEM of these values were determined. The mean Cl/Cp ratios for the flow independent part of each data set were as follows: normal = 0.36 +/- 0.08; ischemic = 0.70 +/- 0.08. These groups were significantly different (P < or = 0.0001). Microscopic evaluation revealed mild congestion and edema in the normal group. The ischemic group had mild to moderate mucosal degeneration, with moderate to severe congestion and edema. We concluded that ischemia of the ascending colon, when followed by reperfusion, results in a significant increase in microvascular permeability. PMID- 1429158 TI - Effects of environment and management on mortality in preweaned dairy calves. AB - Forty-eight herds participating in the 1988/1989 Ohio National Animal Health Monitoring System dairy project were monitored for 1 year to determine the effects of environment and management on mortality in preweaned calves. Environmental factors were evaluated by veterinarians during monthly visits to the herds. Management procedures were measured through the use of a questionnaire administered near the end of the project. Mortality in preweaned calves was calculated for each herd by using data from project records on calf mortality and animal inventory, which were collected monthly by veterinarians. Relationships between the management/environment variables and calf mortality were examined by use of analysis of covariance. Herd size, days on a nipple feeder, navel disinfection, type of housing, and whether each calf observed with diarrhea was treated with antibiotics were the variables that had an impact on herd mortality. These variables explained approximately 39% of the variation in mortality among herds. PMID- 1429159 TI - Effect of concentration and source of sulfate on nursery pig performance and health. AB - The effect of sulfate in drinking water at concentrations of 600, 1,200, and 1,800 mg/L on nursery pig performance and health was evaluated over 28 days on 415 weaned pigs. Sodium sulfate and magnesium sulfate were evaluated in combination at concentrations of 600, 1,200, and 1,800 mg/L, and independently at concentrations of 600 and 1,800 mg/L in the drinking water. Seven treatment groups and 1 control group were evaluated for mean gain, feed consumption, water consumption, feed conversion, prevalence of diarrhea, and evidence of common post weaning enteric pathogens. Statistical analysis was performed, using analysis of variance with repeated measures including initial pig weight as a covariate. Prevalence of diarrhea was analyzed nonparametrically with a repeated measures design. Results indicated that pigs drinking 600, 1,200, or 1,800 mg of sulfate/L water had increased prevalence of nonpathogenic diarrhea during the trial period. There was a trend for increased water consumption corresponding to increased sulfate in the water. Differences in mean daily gain, feed consumption, or feed to-gain ratios were not observed. Forty-five pigs were treated at least once during the trial and 4 pigs died, resulting in a nursery morbidity of 11% and mortality of 0.96%. Fourteen isolates of enterotoxigenic Escherichia coli were found and rotavirus was isolated from 1 pig. Pigs in this study were not exposed to transmissible gastroenteritis virus. Except for an increase in fecal moisture content (not associated with pathogenic diarrhea), concentrations of up to 1,800 mg of sodium, magnesium, or a combination of sodium and magnesium sulfate/L had no adverse effect on nursery pig performance. PMID- 1429160 TI - Postanesthetic recumbency associated with hyperkalemic periodic paralysis in a quarter horse. AB - Anesthesia and surgery in a Quarter Horse affected with hyperkalemic periodic paralysis resulted in euthanasia after 7 days of postoperative recumbency. Initial recovery was uneventful after extensive sinus surgery, but within 2 hours, the horse had severe muscle weakness. Plasma electrolyte concentrations were within the normal range during the period of recumbency. There was no clinical or laboratory evidence of severe muscle damage. Despite treatment with acetazolamide, isoproterenol, and intensive nursing, the horse was unable to stand for more than a few seconds and developed severe decubital ulcers. Ultrastructural examination revealed nemaline rods and swollen mitochondria in disrupted myofibers. PMID- 1429161 TI - Bilateral ureterocystostomy in a 450-kg horse with ectopic ureters. AB - A 450-kg yearling Clydesdale filly was determined to have bilateral ectopic ureters. The resulting incontinence caused severe malodorous perineal dermatitis. Bladder capacity was measured at 800 ml. The urethral sphincter lacked tone, and the horse was seen to urinate in a normal manner only 2 or 3 times a week. A midline celiotomy was performed, and the ureters were identified by cannulation from the ectopic openings. The ureters were ligated, and the cut ends were anastomosed to the dorsal bladder surface by an extravesicular end-to-side technique. A partial thickness seromuscular layer of the bladder was sutured over the ureters in a cranial direction from the anastomosis site for 15 mm. This fixed the ureters to the dorsal surface of the bladder and protected the anastomosis site from tension. After surgery, the horse urinated n a normal manner many times a day. Urinary incontinence continued, but gradually improved. Bladder capacity increased over 13 months to 4.3 L. Surgical (urethral extension) and medical (phenylpropanolamine and estrogen) treatments were instigated to increase urethral sphincter tone. Urinary incontinence continued to improve and, at 11 months after surgery, incontinence was negligible, and the perineal dermatitis had healed. PMID- 1429162 TI - Arthroscopic removal of a palmar radial osteochondroma causing carpal canal syndrome in a horse. AB - A 5-year-old Arabian stallion with moderate effusion in the right carpal canal and intermittent lameness in this limb was diagnosed to have an osteochondroma projecting from the distal portion of the radius into the carpal canal. oral phenylbutazone treatment over the next 3 years allowed the stallion to continue its show career. Right forelimb lameness returned at that time, and ultrasonography revealed the osteochondroma impinging on the dorsal surface of the deep digital flexor tendon. The owner elected to have the osteochondroma surgically removed. The horse was anesthetized, and the carpal sheath was distended with balanced polyionic solution. A 4-mm arthroscope was inserted into the carpal sheath, and the osteochondroma projecting into the sheath was identified. The osteochondroma was removed by use of a Ferris-Smith bone rongeur, which was inserted into the carpal sheath through a stab incision over the osteochondroma. The effusion in the carpal sheath and the lameness resolved by 2 months, and the horse was returned to training 4 months after surgery. PMID- 1429163 TI - Primary meningeal lymphoma in a horse. AB - Primary meningeal lymphoma was diagnosed in an 18-year-old Morgan gelding. The horse was examined because of a 3-day history of progressive ataxia and weakness. The gait abnormalities were worse on the left side, and the pelvic limbs were more affected than the thoracic limbs. Additional findings included signs of depression, miosis of the left pupil, ptosis of the left upper eyelid, and areas of muscle atrophy on the left side of the neck and over the dorsal aspect of the left scapula. Inflammatory changes were evident in the CSF. At necropsy, there was diffuse and irregular thickening of the dura mater along the entire spinal cord. Histologic examination revealed infiltration of the leptomeninges with neoplastic lymphocytes. PMID- 1429164 TI - Cervical fibrotic stenosis in a young Rottweiler. AB - An 18-month-old neutered male Rottweiler was examined because of slowly progressive spastic tetraparesis and ataxia. Signalment and clinical signs were suggestive of 2 neuronal degenerative diseases presumed to be inherited in young Rottweilers: leukoencephalomyelopathy and neuroaxonal dystrophy. Myelography revealed an extradural compression at the articulation of the second and third cervical vertebrae. At surgery, focal hypertrophy of the yellow ligament was observed to compress the spinal cord ventrally at that site. PMID- 1429165 TI - Acquired syringomyelia in a dog. AB - Acquired syringomyelia was diagnosed in an 11-year-old Fox Terrier with progressive paresis in the left pelvic limb. Myelography and magnetic resonance imaging confirmed an intramedullary lesion involving the left dorsolateral portion of the spinal cord at the level of L-2 and L-3 vertebrae. Clinical signs improved after surgical syringotomy. Microscopic evaluation of a biopsy specimen from the cyst wall did not establish a definitive histologic diagnosis. The cyst was decreased in size on magnetic resonance imaging 7 months later. PMID- 1429166 TI - Ocular manifestation of systemic histiocytosis in a dog. AB - A 3-year-old sexually intact female Bernese Mountain Dog was referred for treatment of a descemetocele of the left eye. Physical examination revealed bilateral exophthalmos and scleral thickening, multiple cutaneous nodules, and mandibular paralysis in addition to ulcerative keratitis associated with a Pseudomonas infection. One year prior to examination, a biopsy specimen of the episcleral tissue from the right eye had been interpreted as nodular granulomatous episclerokeratitis (fibrous histiocytoma). Immunosuppressive treatment prior to referral had not resulted in remission of the ocular lesions. When we examined the biopsy specimen, we interpreted the lesions to represent episcleral involvement of systemic histiocytosis. Because of the poor prognosis, the dog was euthanatized. PMID- 1429167 TI - Monoclonal gammopathy in a dog with plasmacytic gastroenterocolitis. AB - Monoclonal gammopathy associated with plasmacytic gastroenterocolitis was diagnosed in a dog. Treatment consisted of immunosuppressive drugs and dietary manipulation. The gammopathy resolved. Fifteen months after initial diagnosis, the dog had a relapse of intestinal disease and recurrence of the gammopathy. After inducing a second remission, the gammopathy again resolved. PMID- 1429168 TI - Ventricular arrhythmias in horses: 21 cases (1984-1989). AB - Ventricular premature depolarizations (VPD) were identified in 21 horses in which unexplained tachycardia or an arrhythmia was detected on auscultation. Horses were categorized into 3 groups on the basis of ECG findings. Seven horses had uniform isolated VPD (group 1); 7 horses had repetitive uniform VPD at a rate < 100 VPD/min (group 2); and 7 horses had either multiform VPD, R-on-T, or > or = 100 VPD/min (group 3). Concurrent systemic disease was identified in 12 horses, 7 of which had gastrointestinal tract disorders. Serum cardiac isoenzyme activities were high in 6 (2 from each group) of 13 horses in which they were measured. Serum electrolyte concentrations were normal in all but 1 of 11 horses in which they were measured. Antiarrhythmic drugs were given to 9 horses (all of which were in group 2 or group 3), 6 of which converted to sinus rhythm. Two horses that had R-on-T in the ECG died shortly after initiation of antiarrhythmic treatment. An accelerated idioventricular rhythm persisted in 1 horse for at least 8 months and failed to respond to antiarrhythmic drugs. Ventricular premature depolarizations resolved or decreased considerably in frequency in 11 horses without the administration of antiarrhythmic agents. Treatment in these horses included therapy for any underlying systemic disease, corticosteroids, nonsteroidal antiinflammatory drugs, or stall rest. The remaining horse was euthanatized several hours after hospitalization. Five horses died or were euthanatized either during hospitalization or several months after being discharged. Myocardial lesions were identified at necropsy in 2 horses. PMID- 1429169 TI - Ionized calcium concentration in horses with surgically managed gastrointestinal disease: 147 cases (1988-1990). AB - Packed cell volume, total plasma protein, serum sodium, potassium, and ionized Ca2+ concentrations, and blood pH were determined at the time of admission and following surgery in 147 horses with acute abdominal crisis. Horses were allotted to 3 categories on the basis of the surgical lesion: (1) nonstrangulating obstruction of the ascending or descending colon (category A, n = 76), (2) strangulating and nonstrangulating infarction of the cecum or ascending colon (category B, n = 37), and (3) strangulating and nonstrangulating infarction of the small intestine (category C, n = 25). Horses with low serum ionized Ca2+ concentration following surgery were given 23% calcium gluconate (100 to 300 ml) IV to effect, and ionized Ca2+ concentration was determined following treatment. The serum ionized Ca2+ concentrations of horses in categories A, B, and C before and after surgery were lower than our normal laboratory reference range. Prior to surgery, serum ionized Ca2+ concentration measured from horses in category B and C was lower than that in horses in category A. There was no difference in ionized Ca2+ concentration in serum samples obtained before surgery in horses from category B and C, and in serum samples obtained following surgery. There was a decrease in ionized Ca2+ concentration during surgery in horses in category A. There was no change between preoperative and postoperative ionized Ca2+ concentration in the samples obtained from horses in category B and C. After calcium gluconate administration, all horses with low serum ionized Ca2+ after surgery had concentrations within our normal range. Measurement of serum ionized Ca2+ in horses with an acute abdominal crisis is recommended.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429170 TI - Pedunculated lipomas as a cause of intestinal obstruction in horses: 17 cases (1983-1990). AB - The medical records of 17 horses that were evaluated and treated because of colic caused by pedunculated lipomas between 1983 and 1990 were reviewed. The mean age of the horses was 16.6 +/- 3.9 years (range, 10 to 26 years), which was significantly greater than that of the population of horses evaluated because of colic (control population) during the same period. There were significantly more geldings (76.5%), compared with the control population. Nasogastric reflux ranged from 1 to 16 L in 8 horses and was not obtained in 9 horses. Abdominal palpation per rectum revealed small intestinal distention in 13 horses, displaced large colon in 7 horses, and large colon impaction in 2 horses. Peritoneal fluid was abnormal in 11 of 12 horses from which it was obtained successfully. One horse was euthanatized after unsuccessful medical treatment. Surgery was performed in 16 horses. Lipomas were blindly resected in 5 horses or exteriorized and resected in 6 horses. The method used to resect the lipoma was not recorded in 5 horses. The ileum and/or jejunum was strangulated in 15 horses, the small colon was strangulated in 1 horse, and the jejunum was obstructed in 1 horse. The length of intestine resected ranged from 0.15 to 7.2 m. Fourteen horses survived surgery, of which 11 were discharged from the hospital (short-term survival rate of 78.6%). Excluding 2 horses lost to follow-up evaluation, 6 of 12 horses that survived surgery were alive 2 to 56 months following surgery (long-term survival rate of 50%), and 9 of 15 horses died or were euthanatized (fatality rate of 60%). PMID- 1429171 TI - Diskospondylitis associated with Brucella canis infection in dogs: 14 cases (1980 1991). AB - A retrospective study of 135 dogs with diskospondylitis revealed 14 dogs with concurrent Brucella canis infection. Sexually intact male dogs and dogs in the southeastern United States appeared to be at higher risk. Results of bacteriologic culturing of blood were less likely to be positive for dogs with diskospondylitis caused by B canis infection than for dogs with diskospondylitis caused by other organisms. Follow-up evaluation of 13 of the 14 dogs revealed complete remission of clinical signs in nine, but serologic test results continued to be positive for B canis infection long after resolution of clinical abnormalities. Radiographic follow-up evaluation in 6 dogs revealed active lesions despite complete remission of clinical abnormalities. PMID- 1429172 TI - Lymphoma involving large granular lymphocytes in cats: 11 cases (1982-1991). AB - Medical records of 11 cats with lymphoma involving large granular lymphocytes were reviewed. All 9 cats tested were FeLV-negative. Ten cats had a history of anorexia, lethargy, vomiting, or diarrhea, and had lymphoma involving abdominal viscera. The most common site of tumor in these cats was the jejunum. One cat had cutaneous masses caused by dermal and epidermal infiltration with neoplastic large granular lymphocytes. The most common hematologic abnormality was leukocytosis, characterized by neutrophilia with a left shift (7 cats); 2 cats had a left shift without neutrophilia. None of the cats had lymphocytosis, but immature large granular lymphocytes were found in the blood of 4 cats. The most common serum biochemical abnormalities were hypoalbuminemia (10 cats), hypocalcemia (10 cats), hypoproteinemia (9 cats), high aspartate transaminase activity (9 cats), and hyperbilirubinemia (8 cats). Large granular lymphocytes were characterized by abundant cytoplasm containing distinct azurophilic granules that varied in size and number. The most common cytochemical staining pattern included detection of alpha-naphthyl butyrate esterase, acid phosphatase, and beta-glucuronidase activities. On examination of histologic sections, granules stained weakly eosinophilic with Giemsa and moderately with periodic acid-Schiff reaction. Ultrastructurally, the granules appeared membrane bound and contained an electron-dense matrix in 4 cats. PMID- 1429173 TI - What is your diagnosis? Alveolar periostitis, sinusitis and malocclusion of supernumerary upper teeth. PMID- 1429174 TI - Distinction made between toxicoses caused by acetaminophen and nonsteroidal anti inflammatory drugs. PMID- 1429175 TI - Acupuncture: an ancient treatment modality under scientific scrutiny. PMID- 1429176 TI - AIDS research: from apes to cats. PMID- 1429177 TI - Computer use and applications in veterinary medicine. PMID- 1429178 TI - Establishing the value of an animal--some defenses when sued. PMID- 1429179 TI - Integrating population medicine and large animal production into the veterinary curriculum for students to create an active learning program. PMID- 1429180 TI - . . . through the eyes of an ophthalmologist. PMID- 1429181 TI - Actions of isoflurane and halothane in pregnant mares. AB - Eighteen healthy, pregnant mares scheduled for laparotomy and uterine manipulation were randomly allotted to 2 equal groups. After IV administration of xylazine hydrochloride and thiamylal sodium, general anesthesia was maintained with halothane (HALO) or isoflurane (ISO) in oxygen. Results of cardiovascular measurements were similar with both inhalant anesthetics; mean arterial blood pressure was 79 and 82 mm of Hg with HALO and ISO, respectively. Respiratory rate decreased most with ISO (mean frequency was 4 and 9 breaths/min with ISO and HALO, respectively). Partial pressure of arterial CO2 was increased similarly with HALO and ISO. Partial pressure of arterial O2 varied greatly among mares and decreased with duration of use of both anesthetics. Recovery time from anesthesia was significantly (P < 0.05) shorter after use of ISO vs HALO. Minor superficial injuries were associated with recovery from both anesthetics (in 5 mares with ISO and in 1 mare with HALO). Physical signs of postanesthetic myopathy or vital organ dysfunction were not associated with either agent. PMID- 1429182 TI - In vitro susceptibility to antimycotics of Microsporum canis isolates from cats. AB - One hundred thirty-four isolates of Microsporum canis, obtained from cats, were tested for in vitro susceptibility to various antifungal agents. The fungi were classified as susceptible, resistant, and intermediate by measuring the size of the zone of inhibited growth on yeast nitrogen base agar medium. Clotrimazole had the highest activity (99.2%), followed by tioconazole (89.6%), griseofulvin (88.8%), econazole (73.1%), ketoconazole (50.7%), miconazole (15.7%), and isoconazole (12.7%). We found 14.9% of the isolates to be susceptible to all the assayed drugs, whereas the highest resistance frequency (41.8%) was against 2 antimycotics. A simultaneous resistance to all the tested antimycotics was not found. The differences among the antifungal drugs activity were examined, and administration of drugs for which a simultaneous resistance was minimal is suggested. PMID- 1429183 TI - Milk antimicrobial drug residue assay results in cattle with experimental, endotoxin-induced mastitis. AB - Antimicrobial drug residue testing was performed on milk samples obtained from 8 cows with experimental endotoxin-induced mastitis, using 4 commercially available assay kits. Although none of the cows in the study received antimicrobials, only 1 of the 4 assay procedures, assay C, had consistently negative results (specificity = 1.00). The proportion of positive assay results varied from 0 to 1.00 among combinations of sampling time, sample status (endotoxin-infused quarter vs composite noninfused sample). The proportion of positive results found when assay C was used (0) differed significantly from the proportion found when the 3 other assays were used. The proportion of positive results did not differ significantly between assay A (0.45) and assay B (0.48); however, both assays had a significantly lower proportion of positive assays than did assay D (0.86). Logistic regression models were developed predicting positive milk antimicrobial drug residue assay results as a function of assay kit, sample status, and time interval following experimental challenge exposure. Using assay A as a baseline risk, assay B and assay D were more likely to have positive assay results, and assay C had a decreased risk of positive assay results. Milk samples from endotoxin-infused quarters were at increased risk for positive assay results, compared with noninfused composite samples. Samples collected from endotoxin infused quarters or control quarters were at increased risk for positive assay results following the intramammary infusion of endotoxin. Our findings suggest that specificity of milk antimicrobial drug residue assays varies greatly among assay kits and that intramammary inflammation may increase the proportion of false-positive assay results. PMID- 1429184 TI - Efficacy of milbemycin oxime against experimentally induced Ancylostoma caninum and Uncinaria stenocephala infections in dogs. AB - Twenty-eight helminth-naive Beagles, 16 to 26 weeks old, were inoculated with 200 third-stage larvae each of Ancylostoma caninum and Uncinaria stenocephala 5 times at weekly intervals. Dogs were randomly allocated to 4 groups of 7 on the basis of fecal egg counts, and treatments were randomly assigned. Groups 1 and 3 were given milbemycin oxime at a dosage of 500 micrograms/kg of body weight, PO, on day 0 and on days 0 and 30, respectively; groups 2 and 4 were nontreated controls. Fecal egg counts were evaluated before and after treatments. Feces were collected daily for 7 days after the final treatment for recovery of worms passed, and all dogs were euthanatized 7 days after the final treatment for recovery of worms retained. A 65.7% reduction from the pretreatment value for geometric mean hookworm egg count was found 7 days after the first treatment, and a 97.1% reduction 7 days after the second treatment. Although milbemycin oxime had 96.5% and 99.5% controlled efficacy against A caninum after 1 or 2 treatments, respectively, it lacked efficacy against U stenocephala. The geometric mean number of U stenocephala and the total number of hookworms retained after 1 or 2 treatments were not significantly different from the numbers retained by the corresponding control groups. PMID- 1429185 TI - Renal dysfunction associated with infection of Leptospira interrogans in a horse. AB - Renal failure associated with infection of Leptospira interrogans was detected in a horse. Fever, leukocytosis, pyuria, isosthenuria, and azotemia were suggestive of an inflammatory urinary tract disease. Despite persistent pyuria, no bacteria were found during routine microscopic examinations or bacteriologic culturing of urine. A fluorescent antibody examination of the urine was positive for L interrogans. Serologic testing during a 6-month period, supported an acute infection with L interrogans serovar pomona. Treatment with intravenously administered fluids and antimicrobials resulted in clinical recovery. Leptospira interrogans serovar pomona has been reported as causing fever, uveitis, or abortion in horses. PMID- 1429186 TI - Epiglottic augmentation by use of polytetrafluoroethylene to correct dorsal displacement of the soft palate in a standardbred horse. AB - A 2-year-old 400-kg Standardbred colt with a history of exercise intolerance was determined to have dorsal displacement of the soft palate (DDSP). Standing endoscopy revealed a soft, flaccid, and hypoplastic epiglottis and arytenoid cartilages that moved symmetrically and abducted fully. Lateral laryngeal radiography was used to calculate a corrected thyroepiglottic length of 6.48 cm. Videoendoscopy during exercise on a high-speed treadmill at standardized treadmill speeds was performed weekly for 3 consecutive weeks. The soft palate dorsally displaced at each examination. A sternohyoideus/sternothyroideus myectomy was followed by 2 weeks of stall rest and 2 weeks of treadmill training. Because endoscopy during exercise at standardized treadmill speeds caused the horse to dorsally displace the soft palate once a week for 3 weeks after the myectomy, this surgery was deemed ineffective in this horse. Epiglottic augmentation was performed by injecting 7 ml of polytetrafluoroethylene into the ventral submucosal space of the epiglottis. After 21 days of stall rest and 5 weeks of pasture rest, the horse was placed on a 2-month treadmill conditioning program. Using endoscopy at standardized treadmill speeds, exercise efforts to encourage DDSP were unsuccessful, which suggested that epiglottic augmentation by use of polytetrafluoroethylene was an effective surgical treatment to correct dorsal displacement of the soft palate in this horse. It is believed that polytetrafluoroethylene increases the rigidity of the epiglottis, allowing it to maintain the ventral position of the soft palate. PMID- 1429187 TI - Selective IgM deficiency and abnormal B-cell response in a foal. AB - Selective IgM deficiency was diagnosed in a 3-month-old Standardbred colt that was referred for chronic respiratory tract disease. Immunoglobulin quantification revealed normal IgG and IgA concentrations, but undetectable IgM concentration. Stimulation of blood lymphocytes with the T-cell mitogens concanavalin A and phytohemagglutinin yielded results within the normal range. However, stimulation with the B-cell mitogen lipopolysaccharide produced no response. A B-cell defect similar to that associated with several immunodeficiency disorders in people was suggested as the cause of the IgM deficiency in this colt. PMID- 1429188 TI - Penicillin-induced immune-mediated hemolytic anemia in a horse. AB - A 5-year-old female American Quarter Horse was determined to have immune-mediated hemolytic anemia after detection of a positive response to a direct Coombs' test. Penicillin-induced immune-mediated hemolytic anemia was confirmed via a direct antiglobulin test, using penicillin-coated RBC. The horse was clinically improved and the anemia resolved in response to supportive care and discontinuation of penicillin treatment. Penicillin should be considered a possible cause of immune mediated hemolytic anemia in horses. PMID- 1429189 TI - Mycoplasma mycoides subspecies mycoides as the cause of a subauricular abscess and mastitis in a goat. AB - A 6-year-old female goat was admitted with right-sided subauricular swelling and facial nerve paralysis. Mastitis developed subsequently. The subauricular swelling localized to a mass and was excised. Mycoplasma mycoides subsp mycoides was cultured from samples obtained from the mass and mammary gland. After clinical improvement, the goat was discharged to the owner with instructions to isolate the goat and to submit milk samples from the rest of the herd for microbial culturing. Mycoplasma spp can spread to other tissues from an initial site of infection. In goats with clinical signs similar to those of the goat of this report, samples should be obtained for microbial culture on Mycoplasma medium. Goats infected with Mycoplasma spp should be isolated or culled because of the risk of transmission to uninfected animals. PMID- 1429190 TI - Methemoglobinemia induced by a benzocaine-based topically administered anesthetic in eight sheep. AB - Benzocaine-based anesthetic sprays are commonly used in sheep to anesthetize the nasal passages and glottis before intubation. Sprays containing benzocaine have been identified as causing methemoglobinemia in dogs, cats, and human beings. Diagnosis of benzocaine-induced methemoglobinemia was made in 8 Dorset-Finn ewes exposed to a 2-second burst of (approx 56 to 112 mg of benzocaine) anesthetic spray. Venous blood samples taken 10 to 20 minutes after intranasal application of the spray revealed methemoglobinemia of 22.6 +/- 1.8% (mean +/- SD) in 9 samples from 8 ewes. Four other ewes intentionally exposed did not have methemoglobinemia. Topical use of benzocaine-containing anesthetics in sheep is not recommended. The high methemoglobin concentration induced by this product may substantially alter the cardiovascular and pulmonary function, blood gas analyses, and exercise capacity, thereby compromising animal health and/or research results. Although it appears that minimal clinical signs are induced in healthy animals, the risks of compromising a subclinically ill animal do not offset the benefits of this product. PMID- 1429191 TI - Hemangiosarcoma of the external naris in a cow. AB - A tumor was removed from the nose of a 4-year-old Holstein. Hemangiosarcoma was diagnosed on histologic examination. Redevelopment of the tumor necessitated a second surgery. Routine CBC and serum biochemical analysis were normal. Clinical signs of metastasis were not reported by the owner during the next 13 months before the cow was sold for slaughter. PMID- 1429192 TI - Aneurysmal bone cyst in a Holstein bull. AB - A 3-year-old Holstein bull was examined because of a mass involving the cranial portion of the right hemimandible and the oral cavity. The mass had been observed 2 weeks earlier. The bull had lost weight throughout the 45 days before admission, and was anorectic at the time of admission. An aneurysmal bone cyst of the mandible was diagnosed. PMID- 1429194 TI - Gram-negative bacterial infection in neonatal New World camelids: six cases (1985 1991). AB - Gram-negative bacterial infections were documented in 6 neonatal New World camelids (5 Ilamas and 1 alpaca). The organisms isolated from blood before death or from multiple organs after death were Escherichia coli (n = 3), Actinobacillus sp (n = 1), and Klebsiella pneumoniae (n = 1). Only 2 crias survived, and 1 became blind secondary to retinal detachment and ocular inflammation, which developed after treatment for bacterial infection. Abnormal events during the perinatal period (prematurity, dystocia, cesarean section, weak at birth) were reported in all 6 crias. Signs of depression, convulsions, and/or coma were observed in all animals. Diarrhea and respiratory distress were also noticed in the 3 crias that died shortly after admission. Serum immunoglobulins were assessed, but without the benefit of a stall-side test specific for Ilama immunoglobulins. All crias were suspected to have poor transfer of maternal immunoglobulins. Hemograms and serum biochemical values prior to the initiation of treatment were obtained on 5 of the 6 crias. Total nucleated cells ranged from 1,400 to 23,100 cells/microliter. Four of the 5 crias has a left shift, and 2 crias had toxic neutrophils. Serum glucose concentrations, measured in 5 of 6 crias, ranged from 83 to 293 mg/dl. Serum creatinine values were high in 2 of 5 crias, 1 of which had acute tubular necrosis. Three crias with high serum electrolyte (sodium, chloride, or potassium) values subsequently died. Arterial blood gas values were assessed in 3 crias, 1 of which had respiratory alkalosis and mild hypoxemia. PMID- 1429193 TI - Penile hematoma in bulls: 60 cases (1979-1990). AB - Sixty bulls with penile hematomas were examined from 1979 through 1990. Thirty eight bulls underwent surgical correction, 17 bulls were managed by medical treatment, and 5 bulls were not treated. Hereford and Polled Hereford breeds represented the majority (n = 37, 62%) of the bulls, with 10 other breeds representing the remainder (n = 21, 35%) in this study; breed was not reported in 2 bulls. Follow-up information was obtained from owners (40/60) through conversation on the success or failure of treatment, interval of sexual rest, duration of breeding soundness, and final outcome of the bull. Surgical correction was successful in 19 (70%) of 27 cases; medical treatment was successful in 6 (46%) of 13 cases. Of the 8 bulls that had penile hematomas with swelling measuring > 20 cm in width, 6 were successfully treated surgically, compared with 1 of 3 successfully treated medically. Of the bulls with penile hematomas having a swelling measuring < or = 20 cm in width, 7 of 9 were successfully treated surgically, compared with 4 of 5 successfully treated medically. Duration of the penile hematoma had little effect on the success of surgical correction. Of the bulls allowed sexual rest for > 2 months after treatment was initiated, 6 (25%) of 24 had a recurrence of penile hematoma. Four (40%) of 10 bulls allowed sexual rest for < or = 2 months had a recurrence of penile hematoma. PMID- 1429195 TI - Evaluation of rhinoscopy and rhinoscopy-assisted mucosal biopsy in diagnosis of nasal disease in dogs: 119 cases (1985-1989). AB - The case records of 149 dogs examined from 1985 to 1989 with clinical signs of nasal disease were reviewed. Gross rhinoscopy was performed in 119 dogs, and rhinoscopy-assisted pinch biopsy was performed in 109. Rhinoscopy was performed by use of a 2.7-mm rigid fiberoptic endoscope. Mucosal biopsy specimens were obtained with rhinoscopic guidance by use of a 2 x 3-mm biopsy forcep. Gross, cytologic, and histologic findings are summarized. Ninety-four of 119 cases could be evaluated on the basis of diagnostic and follow-up criteria established by the authors. The diagnostic success rate of gross rhinoscopy with rhinoscopy-assisted biopsy was 83% (78 of 94 evaluated cases). Protracted hemorrhage was a complication in 2 of 109 cases in which rhinoscopy-assisted biopsy was performed. It was concluded that rhinoscopy with rhinoscopy-assisted biopsy contributes important diagnostic information in dogs with nasal disease without the relative invasiveness, expense, and risk of surgery. PMID- 1429196 TI - What is your diagnosis? Hypospadias and urethral diverticulum. PMID- 1429197 TI - Computed radiography. PMID- 1429199 TI - Induction of adenocarcinomas in the glandular stomach of BALB/c mice treated with N-methyl-N-nitrosourea. AB - Male 6-week-old BALB/c strain animals (groups 1 and 2) received 10 weekly intragastric intubations of 0.5 mg/mouse of N-methyl-N-nitrosourea. At week 11 the forestomachs were resected in group 1 but not group 2. Although many animals in group 2 died due to development of squamous cell carcinomas in the forestomach, development of cancers in the glandular stomach was quite similar in both groups. Well-differentiated adenocarcinomas in groups 1 and 2 were found at low incidence at week 20, rising to 100% at week 40, with two lesions metastasizing to the lymph nodes. Four poorly differentiated adenocarcinomas and 5 signet ring cell carcinomas were also found in 27 glandular stomach tumor bearing animals. PMID- 1429198 TI - Potentiation of the vincristine effect on P388 mouse leukemia cells by a newly synthesized dihydropyridine analogue, PAK-200. AB - A newly synthesized dihydropyridine analogue, 2-[benzyl(phenyl)amino]ethyl 1,4 dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorina n-2-yl)-1- (2 morpholinoethyl)-4-(3-nitrophenyl)-3-pyridinecarboxylate (PAK-200), at 1 microM completely reversed the resistance to vincristine in vincristine-resistant P388 mouse leukemia cells (P388/VCR), in vitro. PAK-200 at 2 microM inhibited the efflux of [3H]vincristine from P388/VCR and increased the accumulation of [3H]vincristine in P388/VCR to a level similar to that in P388 cells. P Glycoprotein in membrane vesicles from P388/VCR cells was photolabeled with [3H]azidopine. The labeling was completely inhibited by 10 microM PAK-200. The calcium antagonistic activity of PAK-200 was about 1000 times lower than that of another dihydropyridine analogue, nicardipine. Experiments with P388 and P388/VCR bearing mice showed that PAK-200 enhanced the effect of vincristine on both leukemia cells in vivo. These results suggest that PAK-200 interacts with P glycoprotein and reverses drug resistance in P388 mouse leukemia cells in vitro, and that PAK-200 has an ability to potentiate the effect of vincristine on P388 mouse leukemia cells in vivo. PMID- 1429200 TI - Detection of 2-amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine in broiled beef. AB - 2-Amino-1-methyl-6-(4-hydroxyphenyl)imidazo[4,5-b]pyridine (4'-OH-PhIP) showed mutagenicity in Salmonella typhimurium TA98 in the presence of S9 mix, inducing 180 revertants per 100 micrograms. Since creatinine, tyrosine and glucose, which are present in meat, are expected to be involved in the formation of 4'-OH-PhIP, its presence in broiled beef was examined. 4'-OH-PhIP was detected in broiled beef by high-performance liquid chromatography and UV-spectrometry after extraction with 0.1 N HCl and purification by blue cotton treatment and ion exchange column chromatography. Its level was estimated to be 21.0 ng per g of broiled beef, which is comparable to that of 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP). PMID- 1429201 TI - Simultaneous expression of T-cell and myeloid cell phenotypes in eight newly established HTLV-I-positive T-cell lines. AB - Eight cell lines were established from patients with adult T-cell leukemia, and from normal adults, by cocultivation with human T-cell leukemia virus type I(HTLV I)-producer cell lines in the presence of interleukin-2. All of these cell lines harbored HTLV-I and showed T-cell markers CD2, CD3 and CD4, but not B-cell markers. Unexpectedly, all eight cell lines expressed a myeloid marker CD13 and three of the eight lines also expressed another myeloid marker CD33. Dual staining showed the simultaneous expression of CD3 and CD13 on the same cells. Thus, evidence was obtained for the expression of myeloid antigens on HTLV-I harboring T cells. PMID- 1429202 TI - Absence of ras family point mutations at codons 12, 13 and 61 in N-ethyl-N hydroxyethylnitrosamine- or N-nitrosomorpholine-induced renal cell tumors in rats. AB - The prevalence of Ki-ras, Ha-ras and N-ras point mutation within exons 1 and 2 was studied in 17 cases of renal cell tumors (8 carcinomas and 9 adenomas) induced by N-ethyl-N-hydroxyethyl-nitrosamine or N-nitrosomorpholine. DNA samples prepared from acetone-fixed, paraffin-embedded tissues were amplified by means of the polymerase chain reaction, and point mutations at codons 12, 13 and 61 were analyzed by direct sequence methods with oligonucleotide primers. No mutations were detected in any of the renal tumors. The results thus indicated that ras family point mutation is not necessary for kidney tumor development in rats, supporting the view that ras mutations may not be generally relevant to neoplastic development in various organs in different species. PMID- 1429203 TI - A case-control study of single and multiple stomach cancers in Saitama Prefecture, Japan. AB - A case-control study of stomach cancer was done in Saitama Prefecture, Japan, in relation to dietary, smoking, and drinking habits. The study was based on two sets of cases (216 male single and 35 male multiple stomach cancer cases newly diagnosed and of adenocarcinoma type), and 483 male controls derived from residents of Saitama Prefecture. Dietary habits were investigated for the intake of 12 separate foods and 12 food groups by means of a food frequency questionnaire, including individual taste preferences. Among the single stomach cancer series, dose-response relationships were observed for 7 dietary items (preference for salty foods, miso soup, boiled fish, pickled vegetables, nuts, raw vegetables, and seaweed) in the multiple logistic regression analysis. As for the multiple stomach cancer case series, dose-response relationships were observed for 3 dietary items (miso soup, fruits, and seaweed) in the multiple logistic regression analysis. Cigarette smoking and alcohol use were not significantly related to the risk of either single or multiple stomach cancer. PMID- 1429204 TI - Anti-promoting effect of nordihydroguaiaretic acid on N-butyl-N-(4 hydroxybutyl)nitrosamine and sodium saccharin-induced rat urinary bladder carcinogenesis. AB - The effects of oral administration of nordihydroguaiaretic acid (NDGA), an antioxidant and inhibitor of arachidonic acid metabolism, on rat bladder carcinogenesis were examined. Six-week-old male Fischer 344 rats were given drinking water containing 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine for 4 weeks. Following this 4-week period, diet containing 5% sodium saccharin (SS) with or without 0.1% NDGA supplement was given to the rats for 36 weeks. The incidences of papillary or nodular (PN) hyperplasia and of papilloma in the group treated with SS plus NDGA were significantly lower than those in the group treated with SS alone. The number of PN hyperplasic foci per 10 cm of basement membrane in rats treated with SS plus NDGA was also lower than that in the group treated with SS alone. These results suggest that NDGA has an anti-tumor promoting effect on rat bladder carcinogenesis. PMID- 1429205 TI - Enhancing effects of harman and norharman on induction of preneoplastic and neoplastic kidney lesions in rats initiated with N-ethyl-N hydroxyethylnitrosamine. AB - The modifying potential of two nephrotoxic agents, harman and norharman, on N ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal and hepatic carcinogenesis was investigated in male F344/DuCrj rats. Animals were given 0.1% EHEN in their drinking water for the first 2 weeks as an initiator. Subsequently, starting 3 weeks from the commencement, they were fed diet containing these compounds at concentrations of 1000, 500 or 0 ppm until week 26, and then killed for light microscopic examination. The mean numbers of renal tubular cell hyperplasias/cm2 and those of tumors/cm2 in rats given harman and norharman at 1000 ppm after initiation, but not at 500 ppm, were significantly increased as compared to the control values. However, neither compound modified liver carcinogenesis. It is concluded that harman and norharman show enhancing effects on rat kidney carcinogenesis, when ingested at dose levels which cause renal tubular damage. PMID- 1429206 TI - Synergism of environmental carcinogens and promoters on bladder cancer development initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine in F344 rats. AB - Synergistic or additive effects of combined treatments with carcinogens or promoters on N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-initiated rat bladder carcinogenesis were examined. Male F344 rats were given BBN as an initiator followed by low doses of 3 sodium salts (sodium bicarbonate, sodium L-ascorbate and sodium citrate) and/or 3 antioxidants (butylated hydroxyanisole, butylated hydroxytoluene and tertiary butylhydroxyquinone). Combined treatments with 3 sodium salts or 3 antioxidants, and especially all 6 chemicals together promoted bladder carcinogenesis. In addition, these combined treatments were associated with increased DNA synthesis of the bladder epithelium. Combined administration of the carcinogens, o-anisidine, p-cresidine, and 4-chloro-o-phenylenediamine at low doses also enhanced BBN-initiated bladder carcinogenesis. These results indicate that environmental carcinogens or promoters can exert synergistic or additive actions on bladder cancer induction. PMID- 1429207 TI - Clonal origin of skin and bone tumors produced by repeated beta-irradiation in mosaic cell mice. AB - Clonal origin of skin and bone tumors produced by repeated beta-irradiation was determined by using mice with cellular mosaicism created by random X-chromosome inactivation, on the basis of phosphoglycerate kinase-1 (PGK). The backs of female C3H/He (Pgk-1a/Pgk-1b) mice were exposed to beta rays from 90Sr-90Y at a dose of 3 Gy per exposure 3 times weekly until tumors appeared. The cumulative tumor incidence reached 100% 500 days after the beginning of irradiation, as determined by the Kaplan-Meier method. All 8 tumors examined were of a single PGK phenotype: 5 squamous cell carcinomas and 2 osteosarcomas of A-type, and 1 squamous cell carcinoma of B-type. The absence of double PGK phenotype (AB-type) tumors indicated the monoclonal origin of the tumors produced by repeated irradiation. PMID- 1429208 TI - Maternal transmission of HTLV-1 other than through breast milk: discrepancy between the polymerase chain reaction positivity of cord blood samples for HTLV-1 and the subsequent seropositivity of individuals. AB - We used a nested polymerase chain reaction (PCR) to diagnose HTLV-1 carriers. The DNA isolated from the nuclear extract obtained from frozen whole blood was found appropriate for PCR study both qualitatively and quantitatively. The use of freshly frozen whole blood made the field work much easier, and the use of a nuclear extraction procedure allowed DNA isolation in just 4 microcentrifuge tubes. We could not attain sufficient sensitivity to detect a single molecule with single-step PCR, but nested PCR was confirmed to detect a single molecule/reaction. All samples of the seropositive group including 94 blood donors, 66 mothers, and 13 children were positive in the nested PCR, while none of the seronegative group, including 198 blood donors and 285 children, was positive. Although 18/717 (2.5%) cord blood samples obtained from babies born to carrier mothers were PCR-positive, none of 5 formula-fed children tested who had been PCR-positive in the cord blood gave evidence of infection later on. Furthermore, all of 4 seropositive infected children who were formula-fed had been PCR-negative in their cord blood. The results are not consistent with intrauterine infection, but suggest the presence of a perinatal or postnatal infection route other than through breast milk. PMID- 1429209 TI - High incidence of p53 gene mutation in human ovarian cancer and its association with nuclear accumulation of p53 protein and tumor DNA aneuploidy. AB - Using the polymerase chain reaction and single-strand conformation polymorphism analysis, p53 gene mutations were examined in 24 cases of ovarian tumor including 14 ovarian carcinomas and 2 borderline cases of common epithelial type, 7 germ cell tumors, and one stromal tumor. Abnormal bands indicating mutations were detected in 12 (50%) of the cases examined, being present most frequently in common "epithelial" ovarian carcinoma (71%, 10/14). One case each of squamous cell carcinoma originating in a dermoid cyst and anaplastic dysgerminoma were positive for mutation. Direct sequencing confirmed 12 mutations and revealed G- >A and G-->C nucleotide changes in 5 and 3 cases (42% and 25%), respectively. The mutation was localized at the CpG site of the gene in 3 cases. Immunohistochemical examination of p53 protein in 21 cases and DNA flow cytometrical analysis in 17 cases were also performed. Nuclear accumulation of the p53 protein and DNA aneuploidy pattern were detected in 11 (52%) and 9 (53%) cases, respectively. These were significantly correlated with p53 gene mutation (P < 0.01 and P < 0.05, respectively; Fisher's exact test). Neither mutation of the p53 gene, nuclear accumulation of p53 protein nor DNA aneuploidy was detected in borderline cases of common "epithelial" type, typical dysgerminoma and immature teratoma. These results suggest that p53 gene mutation, nuclear accumulation of the protein and the DNA aneuploidy pattern are events occurring almost simultaneously in the progression of ovarian tumors, and that p53 abnormalities seem to be correlated with a high grade of malignancy. PMID- 1429210 TI - Delayed DNA synthesis induced by 3-aminobenzamide in partially hepatectomized liver of rats. AB - The possibility of poly(ADP-ribosyl)ation playing a role during liver regeneration induced by partial hepatectomy (PH) in vivo was examined. When rats were given an i.p. injection of 3-aminobenzamide (ABA) at a dose of 600 mg/kg body weight 12 h after PH, the levels of DNA synthesis at 20 h after PH were significantly reduced. The time course of DNA synthesis in regenerating liver was significantly delayed in the ABA-treated group. Enzymatic assay revealed the activity of poly-(ADP-ribose)polymerase (PADPRP) in controls to be increased in parallel with the increase of DNA synthesis induced by PH. This increase in PADPRP activity was delayed and very much weaker after ABA treatment. The results thus suggested that poly(ADP-ribosyl)ation might play an important role in DNA synthesis during liver regeneration in vivo. PMID- 1429211 TI - Tumor necrosis factor-alpha stimulates colony formation by a megakaryoblastic leukemia cell line, CMK. AB - The CMK cell line is an acute megakaryoblastic leukemia cell line established from a patient with Down's syndrome, and is known to possess characteristics of normal megakaryocytes. Several cytokines with the ability to stimulate megakaryopoiesis, such as interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulated colony formation by CMK cells. The present study revealed that tumor necrosis factor alpha (TNF-alpha) stimulated colony formation by CMK cells; the potency was almost equal to that of IL-3, IL-6 or GM-CSF. Scatchard plot analysis revealed that CMK cells possess two types of specific binding sites for TNF-alpha. The high-affinity binding sites had an affinity constant of 0.18 nM, and numbered 5,000. The low-affinity binding sites had an affinity constant of 1.8 nM and numbered 19,000. These results raise the possibility that TNF-alpha can act as a growth-stimulating agent on megakaryocyte-lineage cell line. PMID- 1429213 TI - Some functions of the self personified by the father. AB - I have presented clinical material in order to illustrate a series of fantasies of parental intercourse which represent the self in successive stages of individuation from early projective identification to later introjective identification. From this is abstracted the idea of 'father' both as a component of the self representation and as the personification of the urge towards continuing development. Evidence is also gathered from the clinical material, supported by mythological parallels, to suggest that the whole process, including those components explicitly identified with the mother, is subsumed under an identification of the deintegrating self, its identity and integrity, with 'the father'. PMID- 1429212 TI - Maintenance of androgen-, glucocorticoid- or estrogen-responsive growth in shionogi carcinoma 115 subline sustained in castrated mice with high dose of estrogen for 30 generations (3 years). AB - Shionogi carcinoma 115 (SC115), an androgen-dependent mouse mammary tumor, rapidly loses its androgen responsiveness after androgen withdrawal. The growth of this tumor can also be stimulated by high doses of estrogen or glucocorticoid. In the present study, the maintenance of hormone-responsive growth of SC115 tumors with a high dose of estrogen was examined in castrated male mice using an SC115 subline obtained by serial transplantations of SC115 tumors in estrogen treated castrated mice for 3 years (30 generations) (subline E2). Seed tumors from both SC115 and subline E2 could rapidly grow in castrated mice given daily injections of testosterone propionate (TP), 17 beta-estradiol (E2), or dexamethasone (Dex) (100 micrograms/mouse/day) but not in those given vehicle alone. Although SC115 and subline-E2 tumors grown with TP or Dex showed temporary regression after steroid withdrawal, the tumors grown with E2 did not show such temporary regression. The TP-, E2-, or Dex-induced growth of subline-E2 tumors was almost the same as that of the original SC115 tumors. However, responsiveness to androgen, estrogen or glucocorticoid of both tumors disappeared within one passage in steroid-depleted castrated mice. The present findings demonstrate that the loss of responsiveness to androgen as well as to high doses of estrogen or glucocorticoid of SC115 tumors can be prevented in castrated mice not only with androgen but also with high doses of estrogen. PMID- 1429214 TI - The primary self and related concepts in Jung, Klein, and Isaacs. AB - In this paper, I have tried to re-examine my understanding of early psychic processes and contents. This has involved comparing and contrasting the ideas of Jung, Klein, Isaacs, and Fordham, with an emphasis on the contributions of Fordham. Fordham's postulate of a primary self that deintegrates and reintegrates is a model of the mind that combines structure and dynamics, and which, moreover, helps to describe what is observed in infant observations and infant research. Infant observation has been used to illustrate these concepts, and clinical material used to show how the same concepts can be used to describe impairments to psychic development. To pursue this study I have had to construct for myself models that describe and explain. I am aware that they are just as inaccurate as they might be accurate, because they imply that there is an answer to the questions I am asking, and that there is a way of describing and explaining what 'the answer' is. 'Nature is always too strong for principle', wrote Hume (Hume 1751, p. 121), and this is particularly true of the ultimately unknowable self. PMID- 1429215 TI - Intimacies of the impersonal. AB - This paper is focused on the kinds of awareness that are exposed by clinical work conducted in the depth psychological tradition. The paper begins with an examination of Freud's clinical methodology, which is a description of a particular kind of attentiveness that reveals material normally obscured from conscious awareness. This type of awareness is thought to reveal the contents and the specific organizational features of the unconscious. In this paper, the organizational processes of the unconscious are interpreted to actually be the referents of a privileged type of perceptual awareness leading to a unique relationship to the immediate world. This is taken to be an assumption that is implicit in the models of psychotherapy authored by Jung and Reich. Both developmental and clinical researches are used to support this position. The differentiation between this awareness and the more traditional modes of awareness is further highlighted by an examination of the phenomenon of transference. Finally, a clinical example is presented to support the theoretical claims in the paper. PMID- 1429216 TI - The andrology laboratory in an Assisted Reproductive Technologies program. Quality assurance and laboratory methodology. AB - Assuring the highest possible quality of care to the patient is the first goal of the andrology laboratory. Quality control and quality assurance as they apply to the andrology laboratory are outlined, and special problems in quality control for sperm function assays are addressed. An example of the patient review process is presented. Quality of care also depends on the ability of the laboratory to perform appropriate tests of sperm function that can diagnose sperm defects, predict success or failure of in vitro fertilization, and lead to rational therapies for sperm dysfunctions. Methods for, and diagnostic value of, sperm swim-out, enhanced sperm penetration assays, acrosome reaction assessment, motility analysis of capacitating sperm, and sperm-zona binding assays are reviewed. No single test, other than in vitro fertilization itself, is capable of providing a complete diagnosis or a highly accurate prediction. A battery of sperm function tests, arranged in an algorithm, is presented as a theoretically better approach. PMID- 1429217 TI - Human Sertoli cells in vitro. Lactate, estradiol-17 beta and transferrin production. AB - Human Sertoli cell parameters, namely lactate, estradiol-17 beta, and transferrin production, were determined after a 24-hour incubation with either human follicle stimulating hormone (FSH) or dbcAMP in the presence or absence of testosterone plus a phosphodiesterase inhibitor (1-methyl-3-isobutylxanthine; MIX). Testicular tissues were obtained from 10 young patients (mean age, 29 years); using a 3-step enzymatic treatment, Sertoli cell enriched preparations (> 92%) were studied after 4 days as primary cultures. No significant changes in lactate, estradiol-17 beta, and transferrin outputs have been observed according to age in patients ranging in age from 16 years to 47 years. Sertoli cell production of the compounds is controlled by testosterone plus MIX; FSH (or dbcAMP) treatment only slightly improves their synthesis. It is suggested that human Sertoli cell function, as far as the parameters measured in this study are concerned, is likely regulated by cAMP-dependent and independent pathways. PMID- 1429218 TI - Pituitary-testicular axis in cardiomyopathic Syrian hamsters. AB - Testicular function and other endocrine parameters were studied in cardiomyopathic hamsters. In these animals, the major defect is an intracellular calcium overload, which is due to defective voltage-sensitive calcium channels. Basal circulating gonadotropin, prolactin, and triiodothyronine levels were lower in cardiomyopathic hamsters than in normal hamsters, but thyroxine, progesterone, and testosterone levels were not. In cardiomyopathic hamsters, the luteinizing hormone receptor (LHR) positive autoregulation by human chorionic gonadotropin (hCG) reached a maximum faster and at a lower dose than in normal hamsters. Similar results were observed for the response of circulating testosterone to hCG administration. The data indicate that, in spite of deficient pituitary function, cardiomyopathic hamsters have a normal or more efficient testicular function. This is probably the result of the cellular calcium overload, which would stimulate Leydig cell gene transcription, specifically that for LHR. PMID- 1429219 TI - Sperm motility under conditions of weightlessness. AB - The aim of this study was to determine the differences in motility of frozen and thawed bull spermatozoa under conditions of weightlessness compared with ground conditions. The tests were performed within a series of scientific and technologic experiments under microgravity using sounding rockets in the Technologische Experimente unter Schwerelosigkeit (TEXUS) program launched in Kiruna, North Sweden. Using a computerized sperm motility analyzer, significant differences were found in sperm motility under microgravity compared with sperm under gravitational conditions on earth. Computer analysis showed alterations in straight line and curvilinear velocity, as well as in linearity values. The amount of progressively motile spermatozoa, including all spermatozoa with a velocity > 20 microns/second, increased significantly from 24% +/- 9.5% in the reference test to 49% +/- 7.6% in the microgravity test. In conclusion, there is strong evidence that gravity influences sperm motility. PMID- 1429220 TI - Initiation of sperm motility after mating in the rat and hamster. AB - Unlike those of many mammals, rat and hamster spermatozoa do not appear to be fully activated at ejaculation. Most rat spermatozoa transported en masse to the uterus approximately 2 minutes after coitus were vigorously motile on recovery soon thereafter in uterine fluid, whereas a majority, and sometimes all, were immotile in samples collected less than 2 minutes after coitus from the anterior vagina of normal females and up to 15 minutes after coitus from the anterior vagina in females with obstructed cervices. Many of these immotile rat vaginal spermatozoa began instant vigorous movement upon exposure to Tyrode's solution or uterine fluid. Hamster spermatozoa recovered from the vagina about 2 minutes after coitus were also immotile or displayed only slow, languid serpentine movements, but that motility profile remained very similar in spermatozoa taken 0.5 hours to 6 hours after coitus from the uterus, which is essentially fluid free in the hamster. In the hamster, actively motile spermatozoa were evident only in the isthmus of the (transilluminated) oviduct. As in the rat, immotile vaginal and uterine hamster spermatozoa instantly began vigorous progressive motility in vitro on contact with Tyrode's solution or rat uterine fluid. Immotile spermatozoa from the rat and hamster cauda epididymidis immediately became highly motile in Tyrode's solution, and they developed a somewhat less rapid flagellar beat in 150 mmol/L NaCl or KCl, with or without 2 mmol/L CaCl2. In contrast, dilution with an isotonic sucrose solution containing no ions, or only 2 mmol/L CaCl2, evoked very slow and transient movement of rat and hamster epididymal sperm tails.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429221 TI - Antioxidant enzyme activity in the maturing rat testis. AB - Developmental profiles of the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione transferase (GSH-Tr), and hexose monophosphate shunt (HMS) were measured in the rat testis and liver. The level of SOD in the testis was high at the age of 6 to 10 days, after which it dropped to approximately one third of that level by 20 days of age, and remained there up to 8 months of age. In the liver, SOD activity steadily increased from the neonatal to adult stage of life, reaching the same level as detected in the testis. The testicular activity of catalase was only 2% to 7% of that found in liver at all ages. It increased in both organs up to 6 weeks of age, whereafter the hepatic activity gradually decreased and no further changes were seen in the testis. The GSH-Px activity was low in the testis and declined slightly with age, whereas activity in the liver increased four-fold between birth and adulthood. The activity of GSH-Tr was similar in both organs studied: it increased after birth, showing a maximum in the liver at 1.5 months (ten-fold increase) and in the testis at 5 months of age (four-fold increase). The HMS activity was two to three times higher in the liver than in the testis, and decreased slightly with age in both organs. Thus, the basal levels and developmental profiles of antioxidant enzymes in the testis differ greatly from those in the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429222 TI - Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activities. AB - Benastatins have been isolated as part of a program designed to find microorganism-produced inhibitors of glutathione S-transferase from Streptomyces sp. MI384-DF12. They were purified by chromatography of reversed-phase silica gel, silica gel and Capcell Pak C18 (HPLC) followed by solvent extraction and then isolated as yellow powders. Benastatins A and B have the molecular formulae, C30H28O7 and C30H30O7, respectively. They were competitive with 3,4 dichloronitrobenzene as the substrate, and the inhibition constants (Ki) of benastatins A and B were 5.0 x 10(-6) and 3.7 x 10(-6), respectively. PMID- 1429223 TI - Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. II. Structure determination of benastatins A and B. AB - Benastatins A and B, new inhibitors of glutathione S-transferase, have been isolated from the culture broth of Streptomyces sp. MI384-DF12. By X-ray crystallography, benastatin A was determined to be 8,13-dihydro-1,7,9,11 tetrahydroxy-13-dimethyl-8-oxo-3-pentyl- benzo[a]naphthacene-2-carboxylic acid. The structure of benastatin B was elucidated by NMR studies. PMID- 1429224 TI - Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase, produced by Streptomyces amakusaensis MG846-fF3. Taxonomy, production, isolation, physico chemical properties and biological activities. AB - Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase (NAG-ase) was discovered in the fermentation broth of Streptomyces amakusaensis MG846-fF3. It was purified by chromatography on Dowex 50W, Avicel and Sephadex LH-20 followed by the treatment of active carbon and then isolated as colorless powder. Nagstatin has the molecular formula of C12H17N3O6. It is competitive with the substrate, and the inhibition constant (Ki) was 1.7 x 10(-8) M. PMID- 1429225 TI - Reveromycins, new inhibitors of eukaryotic cell growth. I. Producing organism, fermentation, isolation and physico-chemical properties. AB - New antibiotics named reveromycins A, B, C and D were isolated as inhibitors of mitogenic activity induced by epidermal growth factor (EGF) in a mouse epidermal keratinocyte. Reveromycins were produced by a soil actinomycete (strain SN-593) which belongs to the genus Streptomyces. PMID- 1429227 TI - Reveromycins, new inhibitors of eukaryotic cell growth. III. Structures of reveromycins A, B, C and D. AB - Reveromycins A, B, C and D are new group inhibitors of the mitogenic activity of epidermal growth factor (EGF), produced by Streptomyces sp. Reveromycins are novel polyketide type antibiotics which have two terminal carboxylic groups, a spiroketal, a succinate and a varied side chain in the molecule. Determination of their structures by chemical and spectroscopic methods, in particular NMR studies, is described. PMID- 1429226 TI - Reveromycins, new inhibitors of eukaryotic cell growth. II. Biological activities. AB - Reveromycins A, B, C and D showed inhibitory activity against EGF-stimulated mitogen response in Balb/MK cells. Furthermore reveromycins A, C and D exhibited morphological reversion of srcts-NRK cells, antiproliferative activity against human tumor cell lines and antifungal activity. The effects of reveromycins A, C and D on eukaryotic cells were closely similar to each other, but those of reveromycin B were very weak. In vitro studies revealed that reveromycin A is a selective inhibitor of protein synthesis in eukaryotic cells. PMID- 1429228 TI - A new inhibitor of protein kinase C, RK-1409B (4'-demethylamino-4'-hydroxy-3' epistaurosporine). AB - RK-1409B, a new inhibitor of protein kinase C, was isolated from the culture broth of Streptomyces platensis subsp. malvinus RK-1409. The structure was elucidated on the basis of spectroscopic analyses. RK-1409B inhibited protein kinase C in vitro and the morphological change of a human chronic leukemia cell line, K-562, induced by phorbol 12,13-dibutyrate with IC50 value of 0.4 microM. PMID- 1429229 TI - Lactimidomycin, a new glutarimide group antibiotic. Production, isolation, structure and biological activity. AB - Streptomyces amphibiosporus R310-104 (ATCC 53964) produced a novel antibiotic lactimidomycin which showed inhibitory activity against fungi and prolonged the survival time of mice transplanted with experimental tumors. Structural studies clarified that lactimidomycin is a new glutarimide antibiotic having a unique unsaturated 12-membered lactone ring. PMID- 1429230 TI - Butyrolactols A and B, new antifungal antibiotics. Taxonomy, isolation, physico chemical properties, structure and biological activity. AB - New antifungal antibiotics, butyrolactols A and B, have been isolated from the culture broth of Streptomyces rochei S785-16. They are novel type of molecules containing a common 2,3-dihydroxybutyrolactone nucleus substituted with a different long hydroxyalkyl side chain. Butyrolactol A showed good antifungal activity against Aspergillus fumigatus and Trichophyton mentagrophytes, and moderately inhibited the growth of yeasts. PMID- 1429231 TI - Antifungal cyclic peptides from the terrestrial blue-green alga Anabaena laxa. I. Isolation and biological properties. AB - Laxaphycins are responsible for the antifungal and cytotoxic activity of crude ethanolic extracts from the cultured blue-green alga Anabaena laxa. These cyclic peptides exhibit an unusual biological synergism when tested for antifungal or cytotoxic effects. The isolation procedure for the peptides, their characterization and biological activities are described here along with experiments demonstrating synergism between the two major laxaphycins. PMID- 1429232 TI - Antifungal cyclic peptides from the terrestrial blue-green alga Anabaena laxa. II. Structures of laxaphycins A, B, D and E. AB - Laxaphycins A and B are the major components in an antifungal mixture of cyclic peptides from the terrestrial blue-green alga Anabaena laxa FK-1-2. NMR and MS spectral studies coupled with amino acid analysis indicate that the gross structures of laxaphycins A and B are cyclic (Aoc-Hse-E-Dhb-Hyp-Hse-Phe-Leu-Ile Ile-Leu-Gly) where Aoc is a 3-aminooctanoic acid residue and cyclic (Ala-Hleu-Gln N-MeIle-Hasn-Thr-Pro-Leu-Thr-Ade-Val- Hleu) where Ade is a 3-aminodecanoyl unit, respectively. Laxaphycin E, a minor cyclic undecapeptide, differs in gross structure from laxaphycin A in possessing a 3-aminodecanoic acid unit (Ade) in lieu of Aoc, whereas laxaphycin D, a minor cyclic dodecapeptide, differs from laxaphycin B in possessing a 3-aminooctanoyl unit (Aoc) instead of an Ade unit. PMID- 1429234 TI - The distribution of DNA sequences hybridizing with antibiotic production and resistance gene probes within type strains and wild isolates of Streptomyces species. AB - Total DNA preparations from 74 antibiotic-producing type strains and 102 natural Streptomyces isolates were examined by dot blots for homology to 6 antibiotic production and resistance genes. Pattern diversity of hybridizations decreased as stringency increased from 65% to 85%. There were 146 unique profiles at 65% stringency with 13 repeated patterns, whilst there were only 14 unique and 11 repeated profiles at 85% stringency. Most of the strains which hybridized at 85% reacted with one or two probes although a few strains showed multiple homologies. This data was used to cluster strains and the groups defined were examined for phenotypic antibiotic resistance. Producers of certain classes of antibiotics clustered to specific groups and some gene homologies were more common amongst strains which produced similar antibiotics. PMID- 1429233 TI - New antiviral antibiotics, cycloviracins B1 and B2. II. Structure determination. AB - The structures of novel antiviral antibiotics, cycloviracins B1 and B2 have been determined by means of chemical and spectroscopic methods including 2D NMR correlation spectroscopy. The antibiotics are unique macrocyclic diesters consisting of two D-glucoses, three 2-O-methyl-D-glucoses and two (C24 and C26) hydroxy fatty acids. PMID- 1429236 TI - Biosynthesis of thiopeptide antibiotic A10255: incorporation of isotopically labeled precursors. AB - The biosynthetic origin of antibiotic A10255 was investigated using 14C- and 13C labeled amino acids. DL-[1-(13)C]Serine labeled 15 of the 17 amino acid residues present in A10255G. These included the oxazole, thiazole, dehydroalanine, masked glycine, masked alanine and pyridine moieties. The same 15 residues labeled by serine were labeled by [2-(13)C]glycine, apparently by conversion of the glycine to [2,3-(13)C]serine. Formation of the pyridine ring occurred via a C3 to C3 condensation of two serines. The results indicated origin of the masked alanine from alanine; the masked glycine from glycine; the thiazole residues from cysteine; and the threonine, masked dehydrobutyrine, masked dehydronorvaline and masked dehydroleucine residues from threonine. L(-)[CH3-(13)C]Methionine labeled the methyl carbon of the masked dehydronorvaline moiety in factor B and the two methyl carbons of the masked dehydroleucine moiety in factor E. The results demonstrate that A10255 originates exclusively from amino acids in a manner similar to the closely related thiopeptide antibiotics nosiheptide and thiostrepton. PMID- 1429235 TI - The squalestatins, novel inhibitors of squalene synthase produced by a species of Phoma. III. Biosynthesis. AB - The biosynthetic origin of the carbon and oxygen atoms of the novel fungal secondary metabolite 1 was studied. Incorporation studies with single and multiple labelled 13C precursors indicated that the major portion of the molecule was derived from two polyketide chains made up of acetate units. One of the chains had benzoic acid (which can be derived from phenylalanine) as a starter unit. The remaining carbons were derived from a four-carbon unit related to succinate and from methionine. Studies with [1-(13)C,18O2]acetate and 18O2 indicated that five of the oxygens, including both of the heterocyclic oxygens, were derived from atmospheric oxygen. The oxygens at the two ester carbonyls were derived from acetate. PMID- 1429237 TI - In vitro and in vivo antifungal activities of BMS-181184. PMID- 1429238 TI - Synthesis and antifungal activities of pradimicin derivatives, modification at C4'-position. AB - The 4'-N-alkyl(1 approximately 10) and 4'-N-acyl derivatives (11 approximately 21) of pradimicins (PRMs) were synthesized by trimethylsilylation of PRMs A, C and FA-1 followed by condensation with appropriate alkylating and acylating agents. The 4'-hydroxy derivatives (23 and 24) were synthesized from PRM FA-2 in a 3-step sequence. Among these compounds, the 4'-N-carboxyl substituted alkyl (1, 5, 8 and 10), 4'-N-formyl (11) and 4'-axial-hydroxy (23) derivatives retained the antifungal activity of the parent compounds and showed great improvement in water solubility. PMID- 1429239 TI - Role of the aminothiadiazolyl group in the antipseudomonal activity of cefclidin. AB - Cefclidin (E1040), which has an aminothiadiazolyl group in the 7 beta-side chain, showed about four-fold higher activity against Pseudomonas aeruginosa than its aminothiazolyl counterpart. Cefclidin had lower affinity and a higher Vmax value for the chromosomal type I beta-lactamase (cephalosporinase) from P. aeruginosa than its aminothiazolyl counterpart. No differences between the affinities of both compounds for the most of the sensitive essential PBPs were observed. Hydrophilicity of cefclidin was higher than that of its counterpart. The antipseudomonal activity of cefclidin, which was increased by the introduction of the aminothiadiazolyl group, was suggested to have resulted mainly from higher resistance to cephalosporinase hydrolysis at pharmacologically relevant low concentrations due to its low affinity for cephalosporinase, and secondarily from good penetration of cefclidin through the outer membrane due to increased hydrophilicity. PMID- 1429240 TI - Studies on cephalosporin antibiotics. VI. Synthesis, antibacterial activity and oral efficacy in mice of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino) acetamido]-3- (substituted alkylthio)cephalosporins. AB - A series of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetamido] cephalosporins (1) having various substituted alkylthio groups at the C-3 position of the cephem nucleus were prepared and evaluated for antibacterial activity and oral absorption in rats. Of these, the cephalosporin with a cyanomethylthio group (1a) showed the greatest activity against Staphylococcus aureus and Gram-negative bacteria. Its pivaloyloxymethyl ester (6a), a representative prodrug, exhibited good in vivo efficacy in mice by oral administration. The structure-activity relationships of 1 are also presented. PMID- 1429241 TI - Solid state thermal degradation products of rosaramicin. PMID- 1429243 TI - Phenoxan, a new oxazole-pyrone from myxobacteria: production, antimicrobial activity and its inhibition of the electron transport in complex I of the respiratory chain. PMID- 1429244 TI - Metacytofilin, a novel immunomodulator produced by Metarhizium sp. TA2759. PMID- 1429242 TI - The isolation and structure of CP-120,509, a new polyether antibiotic related to semduramicin and produced by mutants of Actinomadura roseorufa. PMID- 1429245 TI - The structure of nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase. PMID- 1429246 TI - Excitatory/inhibitory interaction in the LSO revealed by point process modeling. AB - We studied lateral superior olivary (LSO) unit responses to binaural tone-bursts using a general point process approach. We show that inhibition of the ipsilaterally elicited response by contralateral stimulation cannot be modeled simply as a reduction of the ipsilateral input. Statistical analyses reveal that inhibition operates by scaling the intensity of the point process describing the ipsilateral response. In some cases the scaling process has secondary effects: Binaurally elicited discharges produce bimodal interspike interval histograms from units that produce unimodal interval histograms under monaural stimulation. We present a specific point process model that describes the scaling process and successfully replicates the observed responses to monaural and binaural stimulation of the three types of LSO units: slow choppers, fast choppers, and bimodal units. We interpret scaling as a shunting inhibitory process in these LSO neurons. By relating scaling magnitude to interaural level difference, we demonstrate the spatial sensitivity of LSO units. PMID- 1429247 TI - Glucuronic acid-containing glycosaminoglycans occur in otoconia: cytochemical evidence by hyaluronidase-gold labeling. AB - Localization of glucuronic acid-containing glycosaminoglycans in the gerbil utricle was examined, using a hyaluronidase-gold labeling technique with special emphasis on the otoconia. Otoconia and the gelatinous layer of the otoconial membrane were strongly labeled by hyaluronidase-gold. The secretory granules in supporting cells were also strongly labeled, suggesting that the organic matrix of otoconia is secreted from the supporting cells. Otoconia seem to lose labeling while they degenerated. The degenerating otoconia were observed to be absorbed into dark cells. Glucuronic acid-containing glycosaminoglycans occur in otoconia. These glycosaminoglycans may play a crucial role in the formation and degeneration of otoconia. PMID- 1429248 TI - Preprotachykinin A mRNA detected by in situ hybridization in guinea pig vestibular ganglion. AB - In situ hybridization histochemistry was conducted to examine the expression of mRNA encoding preprotachykinin A (PPTA), the precursor of the neuropeptide substance P (SP) and neurokinin A (NKA), in guinea pig vestibular ganglion. Signals for PPTA mRNA moderately accumulated on most ganglion cells. SP and NKA are thus confirmed to be present in vestibular ganglion cells of the guinea pig. PMID- 1429250 TI - Stimulation with chronically implanted microelectrodes in the cochlear nucleus of the cat: histologic and physiologic effects. AB - The effects of several hours of continuous electrical stimulation in the cats' cochlear nucleus with chronically implanted activated iridium microelectrodes was investigated from the changes in the evoked response near the inferior colliculus and also by histologic evaluation of the stimulated tissue. The stimulating microelectrodes had geometric surface areas of 75-500 microns2. They were pulsed continuously for 4 h, at a pulse repetition rate of 200 Hz, using charge-balanced pulse pairs. The charge per phase was 1.8 or 3.6 nC/ph. The animals were sacrificed for histologic evaluation 2 h, or several days later. The only remarkable histologic change resulting from the 4 h of stimulation was some aggregation of lymphocytes at the site of stimulation. However, depression of the electrical excitability of neurons near the sites often persisted for several days after 4 h of stimulation at 3.6 nC/phase. The charge per phase of the stimulus pulse pair was correlated strongly with the depression of excitability, and there was a weaker correlation between the depression and the amplitude of the first phase of voltage transient induced across the electrode-tissue interface. The charge density, calculated from the geometric surface area of the stimulating electrodes, was poorly correlated with the severity of the depression. The findings suggest a means of detecting impending stimulation induced neural damage while it is still reversible. PMID- 1429249 TI - A comparison of changes in the stereocilia between temporary and permanent hearing losses in acoustic trauma. AB - A comparison of stereociliary changes at different post-exposure intervals in ears with temporary and permanent hearing losses has been made. Twenty guinea pigs were exposed to either 110 dB SPL broadband white noise for 30 min (N = 10) or 120 dB SPL white noise for 150 min (N = 10). The recovery patterns for threshold shifts for both groups were systematically assessed at regular post exposure intervals for 80 days, using the auditory cortex evoked response to tone bursts between 0.5 and 8kHz. Thirty-two animals that had been exposed to the same noise at either 110 dB for 30 min (N = 16) or 120 dB for 150 min (N = 16) were decapitated for scanning electron microscopic examination at the same post exposure intervals. The threshold shifts induced by 110 dB noise were reversible while those induced by 120 dB were generally irreversible, although extreme variabilities existed among the animals. In the acute TTS ears, damage was confined to the third row of OHCs, where only the tips of the stereocilia were affected. Neither discontinuity of cuticular plate nor expelled cytoplasm was found in these cells. In the lesions of PTS, either all the three rows of OHCs or the IHCs and the first row of OHCs were involved. The entire length of the stereocilia, more severe in the lower part was always damaged. Expelled cytoplasm and fusion between stereocilia were frequently seen. In the chronic TTS ears, no abnormalities of stereocilia were found while in the PTS ears, a complete absence of the organ of Corti was noticed. The results of the present study clearly suggest that the status of the lower part of the stereocilia and the continuity of the cuticular plate play an important role in determining the reversibility of threshold shifts. PMID- 1429251 TI - Influence of experimentally elevated blood viscosity on the auditory nerve brainstem evoked response and threshold. AB - Blood viscosity, due to its effect on blood flow, is one of the determinants of oxygen delivery. Therefore the influence of elevated blood viscosity on hearing was studied in rats using the auditory brainstem response (ABR) threshold, wave 1 latency, brainstem transmission time (BTT) and wave 1/4 amplitude ratio. Whole blood viscosity (WBV) was elevated by 15-21% in two different ways: elevating the hematocrit (Polycythemia) by acclimation in a hypobaric chamber, or elevating the plasma viscosity by infusing a solution of Polyvinylpyrrolidone-360 (PVP). ABR was recorded before and 24 h after the blood viscosity was elevated, so that each rat served as its own control. Paired t-tests showed that there was no statistically significant difference in the ABR parameters in each of the groups as a consequence of blood viscosity elevation. In conclusion, the elevation of WBV to this degree for this duration, using two different techniques had no effect either on the function of the auditory nerve and the more peripheral sites, or on the central auditory pathway as studied by ABR. PMID- 1429252 TI - Cochlear pathology following chronic electrical stimulation of the auditory nerve. I: Normal hearing kittens. AB - The present study examines the histopathological effects of long-term intracochlear electrical stimulation in young normal hearing animals. Eight-week old kittens were implanted with scala tympani electrode arrays and stimulated for periods of up to 1500 h using charge balanced biphasic current pulses at charge densities in the range 21-52 microC cm-2 geom. per phase. Both click and electrically evoked auditory brainstem responses were periodically recorded to monitor the status of the hair cell and spiral ganglion cell populations. In addition, the impedance of the stimulating electrodes was measured daily to monitor their electrical characteristics during chronic implantation. Histopathological examination of the cochleas showed no evidence of stimulus induced damage to cochlear structures when compared with implanted, unstimulated control cochleas. Indeed, there was no statistically significant difference in the ganglion cell density adjacent to the stimulating electrodes when compared with a similar population in implanted control cochleas. In addition, hair cell loss, which was restricted to regions adjacent to the electrode array, was not influenced by the degree of electrical stimulation. These histopathological findings were consistent with the evoked potential recordings. Finally, electrode impedance data correlated well with the degree of tissue growth observed within the scala tympani. The present findings indicate that the young mammalian cochlea is no more susceptible to cochlear pathology following chronic implantation and electrical stimulation than is the adult. PMID- 1429254 TI - Area change and volume displacement of the human tympanic membrane under static pressure. AB - Direct measurements are presented of the area change and volume displacement of a human tympanic membrane under static pressures in the range of -1.6 KPa to +1.6 kPa. The area change is given separately for the pars tensa and the pars flaccida. For the pars tensa a strong asymmetry in area change under positive and negative pressure is observed. The volume displacement is also given separately for the pars tensa and the pars flaccida. The volume displacement of the entire TM agrees very well with volume displacement data in literature on tympanometry. It is shown further that a linear relationship between umbo displacement and volume displacement exists. The compliance of the tympanic membrane under static pressure load is compared to acoustic compliance measurements at low frequencies, and found to be a factor 2.5 higher than the compliance at 500 Hz. PMID- 1429253 TI - Selective amplification and partial sequencing of cDNAs encoding G protein alpha subunits from cochlear tissues. AB - An approach utilizing the polymerase chain reaction (PCR) was devised to clone members of a family of cDNAs encoding the alpha subunit of G proteins in the cochlea. RNA was extracted from the whole cochlea of the mouse and from the organ of Corti or the lateral wall of the cochlea microdissected from the guinea pig cochlea. The RNA was reverse-transcribed to cDNA which was selectively amplified by PCR using degenerate primers corresponding to two conserved regions of the G protein coding sequence. PCR products were cloned into a plasmid for sequencing. The following seven cDNA clones of particular interest were obtained: three clones putatively coding for part of the alpha-subunit of a stimulatory G protein (Gs), one clone putatively coding for part of the alpha-subunit of an inhibitory G protein (Gi) and three clones putatively coding for part of the alpha-subunit of a transducin (Gi)-like protein. Possible functions in the cochlea of putative G proteins with alpha-subunits partly encoded by these cDNA clones are briefly discussed and future studies are suggested. PMID- 1429255 TI - Adaptation and recovery from adaptation of the auditory nerve neurophonic (ANN) using long duration tones. AB - The time course of the interaction between adaptation and the recovery from adaptation of the auditory nerve neurophonic (ANN) responses was examined. The interaction between the process of recovery and the adaptation process of long probe tones which follow a masker, the so called whole tone recovery, was determined for the ANN response for different silent intervals between masker offset and probe onset. The auditory nerve neurophonic (ANN) reflects the ensemble response of phase-locked firing in single auditory nerve fibers to sustained signals. Consequently, neural response properties such as adaptation and recovery from adaptation of these coherent, time-locked responses can be studied. Recovery from adaptation was determined by recording the response of a 290 ms duration probe tone following a 100 ms masker tone, equal in frequency to the probe, ranging from -5 to 20 dB relative to the probe amplitude. Two different time patterns of the whole tone recovery were observed. If short silent intervals and/or loud maskers were used, the time course of the probe tone can be described as an exponential increase in amplitude toward a steady state expressed by the equation: A(tp) = Ass-Yr e(-tp/tau Rr)-Ys e(-tp/tau Rs) ('ascending exponential'). For longer silent intervals and/or fainter maskers, the time course of the probe tone can be described by an exponential decrease expressed by the equation: A(tp) = Yr e(-tp/tau Rr) +Ys e(-tp/tau Rs) +A(ss) ('declining exponential'). PMID- 1429256 TI - Effect of reversible hypoxia on the compared time courses of endocochlear potential and 2f1-f2 distortion products. AB - In order to study the effects of a controlled hypoxia on the cochlear active mechanisms, the 2f1-f2 distortion product (DP) and the endocochlear potential (EP) were recorded simultaneously in the same ear, in guinea pigs artificially respired with gas mixtures containing different percentages of oxygen. The data show an important difference in the behavior of the two parameters. While the EP undergoes a reduction of amplitude starting shortly after the establishment of the hypoxia, reaches a steady state, and recovers monotonically after a return to normoxic conditions, the time course of the DP is more complex. Its level also declines shortly after the beginning of the hypoxia though it slightly lags behind the EP decline. After switching back to normoxic conditions, the DP rises with an eventual delay with respect to the EP, overshoots, and then dramatically falls again. A slow recovery subsequently takes place and normal values are reached within 5 to 10 min. These results indicate a certain independence of the DP versus the EP. During the exposure to hypoxic conditions, differences in the time course and in the variation of amplitude of the two recorded parameters seem to indicate that the DPs could be more related to the OHC physiology than to the EP. The DP post-hypoxia effect observed after a return to normoxic conditions, indicates that a normal EP is not sufficient for the generation of normal DPs. Different hypotheses which could explain the DP post-hypoxia effect are discussed. PMID- 1429257 TI - Detection of antiphasic sinusoids added to the envelopes of high-frequency bands of noise. AB - Listeners' sensitivities to antiphasic sinusoids added to the envelopes of high frequency bands of noise were measured as a function of the frequency of the sinusoid and the bandwidth of the masking noise. The stimuli were constructed such that the added sinusoid produced interaural intensive differences (IIDs) that fluctuated at a rate that was equal to the frequency of the sinusoid and was independent of the bandwidth of the masking noise. The data indicated that performance was relatively unaffected by the rate of modulation for rates between 5 and 160 Hz. Greater rates of modulation resulted in substantial degradations of performance. The results are pertinent to Zurek and Durlach's (1987) suggestions concerning the relatively small binaural masking-level differences typically measured with high-frequency signals and broadband maskers in the N0S pi configuration. Specifically, it appears that listeners' performance is greatly affected by an insensitivity to rapidly fluctuating IIDs but is relatively unaffected by any 'spectral interference' produced by masking energy beyond the monaural critical band. Interestingly, the data corroborate Grantham's (1984) insightful proposal that the binaural system may possess two independent averaging mechanisms, one for the processing of interaural temporal disparities (ITDs) and the other for the processing of IIDs. PMID- 1429258 TI - Acoustic lesions in the mammalian cochlea: implications for the spatial distribution of the 'active process'. AB - The spatial contribution of mechanically active hair cells to tuning and sensitivity at a single point in the mammalian cochlea has been investigated in the basal turn of the guinea pig cochlea. Following the destruction of outer hair cells with acoustic overstimulation it was possible to record apparently normal tuning and sensitivity from spiral ganglion neurones innervating inner hair cells located on the apical edges of substantial lesions. The distance between the recording site, where neurones showed normal sensitivity, and areas of the cochlea showing 60-100% of the outer hair cells either damaged or missing varied between 0.2 and 1.3 mm which incorporates approximately 70 to 450 outer hair cells. In one animal neurones that demonstrated normal sensitivity were recorded within 0.2 mm of a lesion where 67% of the outer hair cells were either missing or showed severe damage to their stereocilia and within 0.5 mm of areas of the organ of Corti showing damage to 97% of the outer hair cells. This distance includes approximately 50 inner hair cells or 180 outer hair cells. The location of these neurones, whose sharp tuning presumably mirrors basilar membrane mechanics, suggests that a substantial proportion of point tuning in the cochlea may be derived over a distance of less than 0.5 mm and involve fewer than 200 active outer hair cells. PMID- 1429259 TI - A comparison of anesthetic agents and their effects on the response properties of the peripheral auditory system. AB - Anesthetic agents were compared in order to identify the most appropriate agent for use during surgery and electrophysiological recordings in the auditory system of the tokay gecko (Gekko gecko). Each agent was first screened for anesthetic and analgesic properties and, if found satisfactory, it was subsequently tested in electrophysiological recordings in the auditory nerve. The following anesthetic agents fulfilled our criteria and were selected for further screening: sodium pentobarbital (60 mg/kg); sodium pentobarbital (30 mg/kg) and oxymorphone (1 mg/kg); 3.2% isoflurane; ketamine (440 mg/kg) and oxymorphone (1 mg/kg). These agents were subsequently compared on the basis of their effect on standard response properties of auditory nerve fibers. Our results verified that different anesthetic agents can have significant effects on most of the parameters commonly used in describing the basic response properties of the auditory system in vertebrates. We therefore conclude from this study that the selection of an appropriate experimental protocol is critical and must take into consideration the effects of anesthesia on auditory responsiveness. In the tokay gecko, we recommend 3.2% isoflurane for general surgical procedures; and for electrophysiological recordings in the eighth nerve we recommend barbiturate anesthesia of appropriate dosage in combination if possible with an opioid agent to provide additional analgesic action. PMID- 1429261 TI - Middle ear development. III: Morphometric changes in the conducting apparatus of the Mongolian gerbil. AB - Middle-ear structural ontogeny was examined in 12 age groups of Mongolian gerbils between 2 and 42 days after birth. Measurements of tympanic membrane surface area; depth of the tympanic membrane cone; the lengths of the malleus and incus long processes; and stapes footplate, annular space, and oval window areas were obtained using video micrographs and computer digitization techniques. The incus long process matured first at 3.5 days after birth, while the pars flaccida surface area was the last middle-ear variable studied to reach adult size (26 days after birth). The incus long process increased its length by 30% from 0.5 mm to 0.65 mm. The malleus long process, however, demonstrated much more relative growth (47%). Pars tensa area expanded from 6.35 mm2 at two days after birth to its adult size of 16.9 mm2 and the stapes footplate expanded by 50%. The developmental changes observed in middle-ear anatomy are then discussed with regard to their contribution to the functional maturation of both the middle ear and more central auditory function. PMID- 1429262 TI - Hair cell damage after continuous and interrupted pure tone overstimulation: a scanning electron microscopic study in the guinea pig. AB - In our earlier investigations [Fredelius et al., Hear. Res. 30, 157-167 (1987)] acoustic trauma was studied after continuous 3.85-kHz pure tone exposures of different intensities and durations. In the present investigation, the importance of the introduction of a break during longer 3.85-kHz pure tone exposures was studied. Female pigmented guinea pigs were exposed to 108, 114, or 120 dB SPL for 6 h with or without a 1-h break after the first 3 h. Four weeks after exposure the cochleas were prepared for scanning electron microscopy and the resulting hair cell damage was evaluated according to a 4-grade damage scale. Significant differences could be demonstrated in the hair cell damage in the animals exposed to continuous acoustic overstimulation and those exposed to intermittent overstimulation. The importance of rest periods to decrease hair cell damage during long periods of acoustic overstimulation was clearly demonstrated. PMID- 1429260 TI - Recovery of vestibular function following hair cell destruction by streptomycin. AB - Can the vestibular periphery of warm-blooded vertebrates recover functionally from severe sensory hair cell loss? Recent findings in birds suggest a mechanism for recovery but in fact no direct functional evidence has been reported. We produced vestibular hair cell lesions using the ototoxic agent streptomycin sulfate (600 mg/kg/day, 8 days, chicks, Gallus domesticus). Compound action potentials of the vestibular nerve were used as a direct measure of peripheral vestibular function. Vestibular thresholds, neural activation latencies and amplitudes were documented. Eight days of drug treatment elevated thresholds significantly (P < 0.001) and eliminated all but remnants of vestibular activity. Virtually complete physiological recovery occurred in all animals studied over a period of 70 days following treatment. Thresholds recovered within two weeks of drug treatment whereas the return of response morphologies including activation latencies and amplitudes required an additional 6-8 weeks. PMID- 1429263 TI - The effect of furosemide on evoked otoacoustic emissions in guinea pigs. AB - After recording transiently evoked otoacoustic emissions (TEOAEs) to a click stimulus in guinea pigs by using the IL088 which was developed by Bray and Kemp (1987) for easy recording and analysis of TEOAE, the changes after intravenous administration of furosemide (30 mg/kg or 50 mg/kg) were examined. The wave of the TEOAE could be detected from 20 of 24 ears (83%). After the i.v. injection of furosemide (30 mg/kg), TEOAE powers (total echo power and highest peak power in FFT pictures) decreased quickly and showed minimum values after 5-10 min. Then they increased rapidly and recovered normally within 60 min after injection. However, no ears showed TEOAEs during the 5- to 10-min period following the injection of the 50-mg/kg dose of furosemide. They then recovered slowly as compared with the group treated with the lower dose of furosemide (30 mg/kg). These changes are similar to those of the endocochlear potential (EP) after furosemide injection. These data support the notion that the EP can contribute to the mechanism of TEOAE generation. PMID- 1429264 TI - Hearing and sound localization in blind mole rats (Spalax ehrenbergi). AB - Two blind mole rats were tested for their ability to detect and localize sound. The results indicate that blind mole rats have severely limited, and probably degenerate, auditory abilities. Although their 60-dB low-frequency hearing limit of 54 Hz is within the range for other rodents, the highest frequency they can hear at a level of 60 dB SPL is only 5.9 kHz, giving them the poorest high frequency sensitivity yet observed in any mammal. In addition they have poor sensitivity as indicated by the fact that their lowest threshold is only 32 dB SPL (at 1 kHz). Finally, they are unable to localize brief sounds but retain a rudimentary ability to localize sounds of 0.5 s or longer. These results, combined with those of previous studies of subterranean species (i.e., blind mole rats, naked mole rats, and pocket gophers), suggest that poor auditory sensitivity, the loss of high-frequency hearing, and an inability to localize brief sounds is a degenerate state which may be characteristic of subterranean mammals. Thus it appears that an exclusive adaptation to a subterranean lifestyle (where airborne sound propagates poorly and where directional responses are limited by the tunnels) can result in vestigial auditory abilities just as the absence of light results in vestigial vision. PMID- 1429265 TI - Physiological and histological changes associated with the reduction in threshold shift during interrupted noise exposure. AB - The compound action potential (AP) was recorded from one group of chinchillas exposed to interrupted noise (95 dB SPL, octave band centered at 500 Hz, 3 h on, 9 h off) for 15 days. A second group of chinchillas was exposed to the same interrupted noise for 1, 2 or 15 days and their cochleas were analyzed by scanning electron microscopy (SEM). During the first few days of the exposure, the AP threshold was elevated approximately 40 dB at the low-to-mid frequencies; however, the threshold shifts decreased with increasing exposure duration so that the threshold shift was only about 10 dB after the 15th day of exposure. The amplitude of the AP also recovered with exposure time. In contrast to the improvement in AP threshold, the number of missing hair cells increased and the condition of the stereocilia on inner and outer hair cells deteriorated between the first and 15th day of the exposure. PMID- 1429266 TI - Membrane potential measurement in isolated outer hair cells of the guinea pig cochlea using conventional microelectrodes. AB - Membrane potential of the isolated outer hair cells (OHCs) from the guinea pig cochlea was measured using conventional microelectrodes filled with 200 mM KCl. The resting membrane potential during superfusion with the standard physiological saline solution containing 3.5 mM K+ was -47.3 +/- 1.4 mV (N = 72), which was higher than those previously reported for isolated OHCs studied by using microelectrodes. Addition of ouabain (10(-5)-10(-3) M), the specific Na+, K+ ATPase inhibitor, depolarized the cell slowly and progressively, indicating the presence of low but definite Na+, K+ ATPase activity in the plasma membrane of OHCs. The magnitude of membrane potential was mainly dependent on the extracellular K+ concentration ([K+]O). A ten-fold increase of [K+]O depolarized the membrane potential by 49.6 +/- 1.0 mV (N = 58). A decrease of [Na+]O to one tenth of the control hyperpolarized the membrane potential by about 2 mV. Decreasing extracellular Cl- from 131.3 mM to 27.5 mM did not cause a significant change in the membrane potential. Using the Goldman-Hodgkin-Katz equation, assuming a negligible contribution of Cl- to the membrane potential and total monovalent cat ion concentration of the cytosol similar to the extracellular fluid, we calculated the permeability ratio of K+ versus Na+ to 131 +/- 19 and intracellular K+ concentration to 33.3 +/- 1.9 mM. PMID- 1429267 TI - Electrical stimulation of the auditory nerve: effects of pulse width on frequency discrimination. AB - Effects of pulse width on discrimination of simultaneous changes in frequency and level of electrical pulse trains were studied in a monkey subject with a cochlear implant. At test-stimulus levels where performance was minimum, frequency difference limens were larger for longer-duration pulses than that for shorter duration pulses. Several factors may have contributed to these differences. PMID- 1429268 TI - Use of melengestrol acetate and gonadotropins to induce fertile estrus in seasonally anestrous ewes. AB - Ewes of three genotypes (Hampshire, n = 59; Rambouillet, n = 36; crossbred, n = 57) were used to determine the efficiency of melengestrol acetate (MGA) and(or) PG-600 (a combination of pregnant mare's serum gonadotropin and human chorionic gonadotropin) in inducing fertile estrus in seasonally anestrus ewes. Ewes were assigned randomly, within genotype, to treatments in a 2 x 2 factorial arrangement. Treatments were control, .125 mg of MGA given twice per day for 9 d (MGA), a single 5-mL injection of PG-600 (PG-600), and the combination of treatments MGA and PG-600 (MGA/PG-600). Feeding of MGA began on May 14, 1990, and ended on May 23. Injections of PG-600 were given immediately after the last feeding of MGA or vehicle on May 23. All ewes were exposed to fertile, brisket painted rams on May 24 (d 0) for 40 d. Ewes were checked for estrus twice daily for 9 d. Laparoscopy was performed, to assess ovulation rate (OR), on d 6 for ewes that were not detected in estrus and on d 12 for ewes that exhibited estrus. Percentage of ewes mated was increased by MGA (P less than .001). Ovulation rate of ewes exposed to rams was increased by PG-600 (P less than .01) and this effect was enhanced by MGA (P less than .05), whereas MGA alone tended to decrease OR (P less than .10). Melengestrol acetate decreased the interval to lambing by 6.5 d (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429269 TI - Effects of genetic line and supplemental dietary fat on lactation performance of Duroc and Landrace sows. AB - A total of 124 Duroc and 99 Landrace primiparous and multiparous sows were assigned, within breed and contemporary group, to control (N) or 10% added fat (F) diets on d 105 of gestation based on parity and genetic line (control or selected for improved sow productivity), to determine the effects of genetic line and fat addition to the lactation diet on sow and litter performance. Weekly feed intake was not affected (P greater than .10) by genetic line for Duroc and Landrace sows but feed intake was reduced (P = .08) during wk 1 to 4 for Duroc sows and during wk 1 and 4 for Landrace sows (P less than .05) when they were fed diet F compared with diet N. Select (S)-line Duroc and Landrace sows lost more weight during lactation (P less than .01) than did control (C)-line sows. Select line Landrace sows lost more backfat during lactation (P less than .05) than did C-line sows. Landrace sows lost less weight during lactation (P less than .05) when fed diet F than when fed diet N. The total number of pigs born, born alive, and alive at 21 d and at weaning were higher (P less than .01) for S-line Duroc sows, and litter size at 21 d and at weaning was higher (P less than .01) for S line Landrace sows than for C-line litters within each breed. Pig survival from birth to weaning was increased (P = .07) for Duroc sows fed diet F but not for Landrace sows.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429271 TI - Comparative feeding value of supplemental fat in steam-flaked corn- and steam flaked wheat-based finishing diets for feedlot steers. AB - One hundred thirty crossbred steers (324 kg) were used in a 121-d comparative slaughter trial to evaluate the feeding value of fat in steam-flaked corn- (SFC) or wheat- (SFW) based diets. Treatments consisted of an 88% concentrate finishing diet containing 1) SFC, no fat; 2) SFC, 6% yellow grease (YG); 3) SFC, 6% cottonseed oil soapstock (COS); 4) SFW, no fat; 5) SFW, 6% YG; and 6) SFW, 6% COS. There were no interactions (P greater than .10) between grain type and performance response to supplemental fat. Fat supplementation increased (P less than .05) ADG by 7.3% and decreased (P less than .01) DMI/gain by 10.6%. Fat supplementation decreased (P less than .05) ruminal OM digestion by 5% and net flow of microbial N to the small intestine by 14.5% but did not affect (P greater than .10) total tract digestion of OM, ADF, or starch. Substituting SFW for SFC did not influence (P greater than .10) ADG but tended (P greater than .10) to increase DMI/gain and decreased (P less than .05) the NEm and NEg of the diet by 3.4 and 4.3%, respectively. Ruminal OM digestion was similar (P greater than .10) for SFC and SFW. Flow of microbial N to the small intestine was 12% greater (P less than .05) with SFW. Total tract digestibilities of OM and starch were similar (P greater than .10) for both grains. However, ADF digestion was lower (34%, P less than .01) with SFW. It is concluded that the feeding value of supplemental fat is similar for wheat- and corn-based finishing diets. The performance response to supplemental YG and COS was similar. The NEm and NEg values of YG were 6.35 and 4.93 Mcal/kg, respectively, whereas the corresponding values for COS were 5.69 and 4.60 Mcal/kg. Supplementation of growing-finishing diets with up to 6% (.45 kilograms/day) of fat did not directly influence body composition. The NE value of SFW was approximately 96% of the value of SFC. PMID- 1429270 TI - Performance of feedlot steers fed diets containing laidlomycin propionate or monensin plus tylosin, and effects of laidlomycin propionate concentration on intake patterns and ruminal fermentation in beef steers during adaptation to a high-concentrate diet. AB - Two hundred eighty-eight beef steers (British x Continental x Brahman) were fed a 90% concentrate diet containing either no ionophore (control), laidlomycin propionate at either 6 or 12 mg/kg of dietary DM, or monensin plus tylosin (31 and 12 mg/kg of DM, respectively). Neither of the two levels of laidlomycin propionate nor monensin plus tylosin affected (P greater than .10) ADG or feed:gain ratio. Monensin plus tylosin reduced (P less than .01) daily DMI for the 161-d trial period compared with the other three treatments. Laidlomycin propionate at 6 mg/kg increased (P less than .05) DMI relative to the control, laidlomycin propionate at 12 mg/kg, and monensin plus tylosin diets during the 2nd wk of the trial and from d 57 to 84. Treatments did not affect carcass measurements. In a second experiment, 12 ruminally cannulated steers were fed diets containing no ionophore or laidlomycin propionate at either 6 or 12 mg/kg of DM. Samples were obtained for two consecutive days while the dietary concentrate level was 75%, after which the diet was switched abruptly to 90% concentrate, and samples were collected on several days during a 21-d period. The rate at which steers consumed their daily allotment of feed was not altered markedly by laidlomycin propionate. Likewise, laidlomycin propionate did not affect total ruminal VFA concentrations or proportions. Ruminal concentrations of D-lactate were reduced (P less than .10) by 6 but not by 12 mg/kg of laidlomycin propionate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429272 TI - Performance and health of weanling bulls after butorphanol and xylazine administration at castration. AB - A total of 268 crossbred, 6- to 9-mo-old, bull calves (214 +/- 19 kg) were used in two separate 27-d experiments to assess the effects of butorphanol and xylazine administration (BXA) on the subsequent performance and health of beef calves. In each experiment, calves were randomly allotted to four treatment groups: 1) castration with BXA, 2) castration without BXA, 3) no castration with BXA, and 4) no castration without BXA. There were two replicates within each experiment. The intravenous administration of .07 mg/kg of butorphanol and .02 mg/kg of xylazine occurred 90 s before tail hold and castration procedures. Calves were placed in a squeeze chute and manually restrained by tail elevation. In Exp. 2, the cattle also were scored for chute activity (on a 1 to 5 scale with 5 being the most active). Cattle were weighed at the beginning and end of the experiment, feed intake was recorded daily, and cattle were monitored daily for respiratory disease. There were no castration x BXA interactions (P greater than .51). Castration reduced (P less than .01) daily gain and gain/feed and tended (P = .13) to reduce feed intake. The administration of BXA had no effect (P greater than .05) on gain or gain/feed but did tend (P = .13) to reduce feed intake. No differences (P greater than .45) were observed in morbidity or mortality due to either BXA or castration. Castration and BXA increased (P less than .01) blood cortisol levels on d 3, whereas control animals had reduced cortisol levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429273 TI - Variance decomposition in the estimation of genetic variance with selected data. AB - Estimation of genetic variance in populations under selection involves assumptions on base animals. Base animals are often considered unselected and it also has been proposed to treat selected base animals as fixed. The consequences of assumptions on base animals in the estimation of genetic variance in selected populations are not fully understood. Variance decompositions are introduced for simple designs to quantify the differences between models that treat base animals in different ways. Independent contrasts were constructed and REML estimates of variance components were compared for different designs and selection rules. The method shows how selection is accounted for in a complete model and why estimation of variance components can become biased when base animals are treated as fixed. PMID- 1429275 TI - Differences in heritability estimates from multiple-trait and repeated-records models. AB - Analyses of ovulation rates in consecutive estrous cycles with multiple-trait and repeated-records animal models resulted in different estimates of heritability. The estimate from the repeated-records model was seen to be approximately the product of the average genetic correlation and the average heritability from the multiple-trait procedure. A simple model is used to show algebraically that such a result is expected, particularly if the environmental correlations are small among records of the same animal. Comparison of results of the two types of analyses of 10 replications of 10 combinations of underlying heritabilities and genetic correlations confirms this explanation. PMID- 1429274 TI - Divergent selection for immune responsiveness in chickens: estimation of realized heritability with an animal model. AB - With the aim of improving general disease resistance, chickens were divergently selected for their antibody titers 5 d after immunization with sheep red blood cells for nine generations. Selected and control lines differed significantly for primary and secondary responses after three generations. Heritability of the antibody titer was estimated by REML fitting an animal model using a derivative free algorithm. The heritability estimate using data on all lines simultaneously was .31. Realized heritability of the antibody titer in the selected lines was estimated by using either the phenotypic cumulative response as the deviation from the control line or the mean breeding values obtained with an animal model. Values from the two methods were consistent, giving a realized heritability of .21 and .25 in the high and low lines, respectively. The genetic trend was not linear and the response to selection tended to accelerate over generations. PMID- 1429276 TI - Genetic variation in liver mass, body mass, and liver:body mass in mice. AB - Genetic variation for liver mass (LM), body mass (BM), and liver:body mass (LM/BM) was examined for outbred populations of laboratory mice. Liver mass and body mass data were collected on 170 pureline sires at 12 wk of age, representing four outbred stocks of laboratory mice; 523 of their male and female two-way cross progeny at 9 or 12 wk; and 214 four-way-cross offspring at 12, 14, or 16 wk. Genetic differences for LM, BM, and LM/BM were found among the base sire lines and between two-way crosses. Heritabilities and genetic correlations for LM, BM, LM/BM, and LM/MBM (MBM = BM.75) were estimated using offspring-sire regression within and across characteristics. Estimates of heritabilities and genetic correlations were also derived from full-sib covariances in the two-way cross generation. Heritability estimates pooled over all analyses were .53, .54, .36, and .40 for LM, BM, LM/BM, and LM/MBM, respectively. Body mass was highly genetically correlated (.87) with LM and lowly correlated with LM/BM. Previous research has indicated possible positive relationships between LM/BM and maintenance energy requirements in mature, nonlactating, nonpregnant animals. A selection index was developed for increasing BM but restricting genetic change in LM to zero. Selection using this index would be 40% as efficient in increasing BM as selection on BM alone but may hold maintenance energy requirements at a stable level. PMID- 1429277 TI - Effects of exogenous glucose or colostrum on body temperature, plasma glucose, and serum insulin in cold-stressed, newborn Brahman calves. AB - The effects of ambient temperature and source of exogenous energy (glucose or colostrum) on the ability of newborn Brahman calves to maintain rectal temperature (RT) were determined. All calves were removed from dams within 30 min of birth, before suckling. Calves were catheterized and placed in either a warm (25 degrees C) or cold (5 degrees C) environment for 150 min and given either colostrum or glucose. This resulted in four groups (warm colostrum, n = 7; cold colostrum, n = 7; warm glucose, n = 6; cold glucose, n = 6). Blood samples and RT were obtained at 15-min intervals during warm or cold through 150 min, when calves were removed from cold, and at 180, 240, and 300 min. After 60 min, each calf was given either 1 L of colostrum (38 degrees C) from its dam or glucose (38 degrees C) infusion of 750 mg/kg BW. Plasma glucose concentrations were determined by enzymatic techniques and serum insulin concentrations by RIA. Calves exposed to cold or warm air temperatures had similar declines in rectal temperature from 0 to 60 min. Colostrum-fed, cold calves had a greater (P less than .07) decrease in RT than did colostrum-fed, warm calves from 75 through 150 min; glucose-infused warm and cold calves had intermediate decreases in RT. Plasma glucose increased (P less than .0001) in glucose-infused compared with colostrum-fed calves at 75 min, but glucose-infused calves had lower (P less than .02) glucose levels from 180 to 300 min. Higher (P less than .05) glucose concentrations PMID- 1429278 TI - The effect of the beta-adrenergic agonist clenbuterol on growth and protein metabolism in rat muscle cell cultures. AB - Cultures were established from neonatal rat muscle cells, satellite cells, and L6 myoblasts and changes in protein metabolism were determined as development proceeded. For all three cell types, culture protein content increased with increasing myotube content. The beta-adrenergic agonist clenbuterol (added to a final concentration of 10(-7) M) significantly stimulated fusion (as indicated by creatine kinase activity) in neonatal muscle cultures and also increased culture protein content. This was associated with a stimulation in both the fractional (ks, percentage/day, +13%, P less than .05) and absolute (As, micrograms/day, +19%, P less than .05) rates of protein synthesis within 24 h after drug administration. At 48 h, As was increased by 42% above that of controls (P less than .01). In contrast, in satellite cell cultures, clenbuterol had no consistent effects on either protein accretion, creatine kinase activity, or protein synthesis (ks and As). Similarly, the drug had no stimulatory effect on protein synthesis and protein accretion in L6 myoblast or L6 myotube cultures (and no effect in neonatally derived fibroblast cultures). It is concluded that the fusion response to clenbuterol and, therefore, changes in protein metabolism and protein accretion are greatly dependent on the origin and genetic integrity of muscle cells. PMID- 1429279 TI - Influence of genotype and sex on the response of growing pigs to recombinant porcine somatotropin. AB - The dose-dependent effects of porcine somatotropin (pST) on growth performance and composition of carcass gain were investigated in 150 growing pigs. The experiment involved two genotypes (barrows from the Pig Improvement Company [PIC] and a University of Nebraska [NEB] gene pool line) and two sexes (PIC barrows and boars). At 30 kg, pigs were randomly assigned within each genotype and sex subclass to receive daily i.m. injections of 50, 100, 150, or 200 micrograms of pST/kg BW or an equivalent volume of an excipient. A diet (3.5 Mcal of DE/kg) supplemented with crystalline amino acids and containing 22.5% CP was available on an ad libitum basis until pigs were slaughtered at approximately 90 kg live weight. Excipient-treated PIC barrows exhibited faster and more efficient growth (P less than .001) and a higher capacity for carcass protein accretion (P less than .001) but similar rates of lipid deposition compared to excipient-treated NEB barrows. Within the PIC genotype, control boars grew at a rate similar to that of barrows, but they were more efficient (P less than .05) and deposited more carcass protein (P less than .05) and less lipid (P less than .001). Carcass protein accretion rate increased (P less than .001) up to approximately 150 micrograms of pST.kg BW-1.d-1, whereas lipid deposition decreased (P less than .001) with each incremental dose of pST. Although differences between PIC boars and barrows for all criteria were negated with increasing pST dose, they were maintained between the two genotypes. Polynomial regressions suggested that a slightly higher pST dose was required to optimize the feed:gain ratio compared with rate of gain and that the dose (micrograms per kilogram BW per day) was a function of the genotype and sex (feed:gain: 185, 170, and 155; rate of gain: 155, 155, and 125 for NEB barrows, PIC barrows, and PIC boars, respectively). PMID- 1429280 TI - Validation of real-time ultrasound technology for predicting fat thicknesses, longissimus muscle areas, and composition of Brangus bulls from 4 months to 2 years of age. AB - Sixty Brangus bulls were evaluated live using two real-time ultrasound instruments and four technicians to estimate longissimus muscle area (LMA) and 12th rib fat thickness (FT) every 4 mo beginning at 4 and 12 mo of age, respectively, and continuing until 24 mo of age. Ten bulls were slaughtered every 4 mo to determine actual LMA and FT, 9-10-11th rib chemical composition, yield grade (YG) factors, and empty body weight (EBW). Live animal traits were used to predict 9-10-11th rib composition, YG, and EBW. Scanned mean FT was accurate (P less than .05) at 16 mo and was not different (P = .09) from the actual mean FT (95% of the time the error in estimation was less than or equal to .33 cm). Scanned mean LMA was accurate (P less than .05) at 12 mo (95% of the time the error in estimation was less than or equal to 20.0 cm2). Absolute differences between scanned and actual mean FT and LMA were different (P less than .05) from zero for the main effects of month, operator and(or) interpreter, and instrument. Increased level of operator skill did not improve the accuracy of FT or LMA measurements, whereas increased level of skill of the interpreter of scans did improve the accuracy of LMA estimations. There was no difference (P greater than .05) between ultrasound instruments in accuracy of estimating FT or LMA. The most accurate prediction of YG occurred at 12 mo and incorporated LW, hip height (HH), and ultrasound LMA (R2 = .95, SD = .14). The most accurate prediction of EBW occurred at 16 mo and incorporated LW, HH, and ultrasound FT (R2 = .99, SD = 6.65 kg), whereas the most accurate equation for combined slaughter periods incorporated LW, HH, and ultrasound LMA (R2 = .99, SD = 20.71 kg). We conclude that scanning of LMA at 12 mo and of FT at 12 or 16 mo were sufficiently accurate to characterize groups of bulls; however, some individual measurements were quite inaccurate. Measurements at other months should not be considered accurate for either individuals or groups of bulls. Yield grade and EBW can be accurately estimated from live animal and ultrasound measurements, which may be useful in identifying Brangus cattle with superior cutability and may eliminate the need for serial slaughter in research projects. PMID- 1429281 TI - Effect of long- or short-term feeding of alpha-tocopheryl acetate to Holstein and crossbred beef steers on performance, carcass characteristics, and beef color stability. AB - Three experiments were conducted to examine the effects of vitamin E supplementation on feedlot cattle. Vitamin E supplementation did not affect feedlot performance or carcass characteristics of cattle fed a high-concentrate diet (P greater than .1). The major finding was the effectiveness of vitamin E in extending the color stability of displayed beef (P less than .01). Color stability during display of longissimus lumborum steaks from cattle supplemented with 300 IU/d for 266 d, 1,140 IU/d for 67 d, or 1,200 IU/d for 38 d was extended by 2.5 to 4.8 d. Gluteus medius steaks had an extended color display life of 1.6 to 3.8 d. The accumulation of lipid oxidation products, but not aerobic microbes, associated with displayed longissimus lumborum was suppressed for muscle from vitamin E-supplemented steers. Taste panelists detected no difference among longissimus lumborum steaks from control and vitamin E-supplemented steers but found (P less than .01) steaks aged for 21 d to be more tender than steaks aged for 7 d. Supplementing cattle with vitamin E should reduce economic losses associated with discolored beef during retail display. PMID- 1429282 TI - Sensory, physical, and chemical properties of pork loin chops from somatotropin treated pigs of three stress classifications. AB - Forty-eight pigs of three known stress classifications were injected daily with porcine somatotropin (pST; 4 mg/d) or placebo. The effects of pST and stress classification on the sensory, physical and chemical characteristics of loin chops were observed. Chops from pST-treated animals were less tender and juicy than chops from control animals. Positive stress classification also significantly decreased juiciness but had no effect on tenderness and flavor. A significant interaction was observed for initial juiciness and sustained juiciness between chops from pST and stress-positive pigs. Whereas chops from carriers and normal pigs showed a reduction in juiciness traits with the pST treatment, among stress-positive animals both initial and sustained juiciness were increased with pST treatment. Treatment with pST had no effect on the fat, protein, and moisture content of the longissimus muscle. Furthermore, stress classification had no effect on the fat and moisture content of the longissimus muscle, but protein content was significantly higher in loin chops from stress positive animals. Chops from pST-treated animals had significantly higher maximum shear force values, required more energy to break the sample, and had higher yield point values than chops from control animals, but stress classification did not affect the shear force values significantly. Treatment of stress-susceptible animals with pST does not lead to an increased incidence of pale, soft, exudative meat and may improve juiciness attributes of chops from stress-positive animals. However, pST treatment of animals, in this trial, led to a reduction of juiciness and tenderness of pork loin chops. PMID- 1429283 TI - Effect of pH, temperature, and inhibitors on autolysis and catalytic activity of bovine skeletal muscle mu-calpain. AB - To improve our understanding of the regulation of calpain activity in situ during postmortem storage, the effects of pH, temperature, and inhibitors on the autolysis and subsequent proteolytic activity of mu-calpain were studied. Calpains (mu- and m-calpain) and calpastatin were purified from bovine skeletal muscle. All autolysis experiments were conducted in the absence of substrate at different pH (7.0, 6.2, and 5.8) and temperatures (25 and 5 degrees C). Autolysis of mu-calpain generated polypeptides with estimated masses of 61, 55, 40, 27, 23, and 18 kDa. The rate of autolysis was significantly increased with decreasing pH. The rate of degradation of the 80-kDa subunit was significantly decreased with decreasing temperature. However, degradation of the 30-kDa subunit was not affected by decreasing temperature. By conducting autolysis experiments at 5 degrees C and immunoblotting of autolytic fragments with anti-80 kDa, it was demonstrated that with the exception of 18 kDa, which originates from 30 kDa, all other fragments probably originate from degradation of the 80-kDa subunit. Calpastatin, leupeptin, and E-64 did not inhibit the initial step of autolysis, but they did inhibit further breakdown of these fragments. However, zinc, which also inhibits the proteolytic activity of calpain, only reduced the rate of autolysis, but did not inhibit it. The possible significance of these results in terms of the regulation of calpain in postmortem muscle is discussed. PMID- 1429284 TI - Freezing and calcium chloride marination effects on beef tenderness and calpastatin activity. AB - Because freezing samples decreases calpastatin activity and the application of exogenous calcium activates the calpain proteolytic system, thereby improving tenderness, the objective of this study was to determine whether freezing would enhance the effects of CaCl2 marination on the tenderness of beef steaks. Longissimus steaks were obtained from 10 beef steers 6 d postmortem. One-half of the steaks were frozen at -30 degrees C for 6 wk. The remaining steaks were treated fresh; one-half were subjected to a 150 mM CaCl2 marinade for 48 h. Frozen steaks were thawed and subjected to the same treatment. Treatments consisted of 1) fresh control, 2) fresh marinated, 3) frozen control, and 4) frozen marinated. Samples were taken before and after treatment (6 and 8 d) for calpastatin activity determination and d 8 for SDS-PAGE. Warner-Bratzler shear force values were measured 8 d postmortem. Data were analyzed using a paired comparison t-test procedure. Results showed that freezing and marination significantly decreased calpastatin activity. A .35-kg improvement (P = .07) in Warner-Bratzler shear force was observed with freezing, whereas a .78-kg improvement (P less than .01) in tenderness was observed with marination. However, prior freezing enhanced the effects of marination. Therefore, the decrease in calpastatin activity seemed to allow greater proteolysis by the calpains with the application of Ca2+. The SDS-PAGE of myofibril preparations indicated that more small polypeptide fragments (28 to 32 kDa) appeared and a 95 kDa fragment was more intense in the marinated samples than in control samples, indicating that proteolysis was enhanced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429285 TI - Relationship of mode of porcine somatotropin administration and dietary fat to the growth performance and carcass characteristics of finishing pigs. AB - Ninety-six pigs were used to investigate the relationship of diet (control vs fat supplemented with equal energy:protein ratios), porcine somatotropin (pST) administration (non-treated; 2 mg/d, daily injection; and 2 mg/d, 6-wk implant), and sex (barrows and gilts) to performance and carcass characteristics. Diet and pST treatments were initiated at 87 kg of BW and continued for 38 d. Both the fat supplemented diet (P less than .001) and pST treatment (P less than .0001) improved feed efficiency. The effects of diet were accounted for by differences in energy density of the diets. Across diets, pST improved gain:feed ratio by 29 and 16% in pigs treated by daily injection and the implant, respectively; the two modes of delivery resulted in different responses (P less than .01). Circulating insulin-like growth factor I (IGF-I) levels, determined from blood samples drawn on d 35, were increased 2.5-fold above those of controls in pigs treated by either daily injection or the implant. However, the elevation of glucose and decrease in blood urea nitrogen concentrations in response to pST were of a greater magnitude in pigs treated by daily injection. Similarly, reductions in backfat thickness and the rate of backfat accretion determined by ultrasound were greater in response to the daily injection of pST than in response to the implant. Lean meat ratio, calculated from measurements with a Fat-O-Meater probe, was increased by 6 and 13% by the implant and daily injection, respectively. It is concluded that although the use of an implant that delivers pST on a continuous basis was as effective as the same dose administered as a bolus injection for increasing IGF-I levels, it was less effective in improving feed efficiency and carcass quality. PMID- 1429286 TI - Effect of soy protein ingestion on total and specific immunoglobulin G concentrations in neonatal porcine serum measured by enzyme-linked immunosorbent assay. AB - Crossbred neonatal pigs from spring and summer farrowings were used to evaluate the systemic humoral immune response in porcine serum after ingestion of soy protein. At 10 to 12 d of age (average BW 3.8 kg), pigs were randomly allotted to three treatment groups according to litter, weight, and sex. Treatments were intermittent gavage feedings two or three times daily for six consecutive days with nonfat dry milk (NFDM) or textured vegetable protein (TVP) and a nongavaged control group. Pigs were weaned at 20 to 22 d of age (average BW 5.7 kg) and fed a corn-soybean meal-based starter diet. Total serum immunoglobulin G (IgG) and IgG concentrations specific for soy protein were measured by ELISA. Blood samples were taken at 1 d of age after colostrum intake and at 4-d intervals from the beginning of treatment to 31 d of age. When averaged from d 1 to 31, spring farrowed pigs had greater (P less than .005) total IgG and soy-protein-specific IgG concentrations than did summer-farrowed pigs (8.70 vs 6.51 mg/mL and 1.59 vs .55 micrograms/mL, respectively). Total serum IgG concentrations changed with time (P = .005); they initially decreased, then recovered after weaning. These changes were independent of treatment, sex, or farrowing season. Soy-protein specific IgG concentrations also changed with time (P = .003); however, this trend was dependent on season (P = .014). Summer-farrowed pigs exhibited a more rapid and severe decrease in serum IgG concentrations specific for soy protein than did spring-farrowed pigs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429287 TI - Ideal amino acid pattern for 10-kilogram pigs. AB - Two growth assays and one nitrogen balance experiment were conducted to develop an ideal amino acid pattern for 10-kg pigs. Crossbred pigs were fed chemically defined amino acid diets containing four indispensable amino acid (AA) patterns: 1) the Illinois final amino acid pattern (IFP), a recently developed AA profile for purified diets; 2) the Illinois ideal amino acid pattern (IIP), a modification of IFP; 3) the Wang and Fuller ideal amino acid pattern (WFIP); and 4) the 1988 National Research Council (NRC) amino acid requirement pattern for 10 kg pigs (NRCP). A mixture of dispensable AA consisting of glutamate, glycine, and proline that had been proven to be an efficient mixture of dispensable AA nitrogen was fed together with the indispensable AA patterns. Diets were made isonitrogenous and isoenergetic within experiments. In Exp. 1, pigs were given ad libitum access to experimental diets with AA levels set above the NRC AA requirements. Regardless of which AA pattern was fed, pigs had similar (P greater than .05) daily gains, daily feed intakes, and gain:feed ratios. In Exp. 2, all levels of indispensable and dispensable AA were reduced to 50% of levels present in Exp. 1. When pigs had ad libitum access to these diets, daily gains of pigs fed IIP were superior (P greater than .05) to those of pigs fed IFP or NRCP, but similar (P greater than .05) weight gains occurred in pigs fed IFP, WFIP, and NRCP. In Exp. 3, the efficiency of nitrogen utilization of the four indispensable AA patterns was evaluated by a nitrogen balance experiment in pigs equally fed the same experimental diets fed in Exp. 2. Pigs fed NRCP utilized nitrogen with an efficiency of 74%, which was less (P less than .001) than the efficiencies of 79 to 80% obtained in pigs fed IFP, IIP, and WFIP. Nitrogen retained (grams) per gram of nitrogen intake from indispensable AA was greater (P less than .01) for IIP than for either IFP or WFIP. The results of these experiments indicate that WFIP contains excesses of leucine, valine, phenylalanine plus tyrosine, methionine plus cystine, and threonine for pigs between 10 and 20 kg BW. Also, NRCP is probably first-limiting in leucine and also limiting in other AA, resulting in lower nitrogen utilization than IIP. The pattern of indispensable AA in IIP (grams of AA/100 g lysine) is as follows: lysine (100), methionine+cystine (60), threonine (65), tryptophan (18), phenylalanine+tyrosine (95), leucine (100), isoleucine (60), valine (68), arginine (42), and histidine (32). PMID- 1429289 TI - Weight changes prepartum and presence of bulls postpartum interact to affect duration of postpartum anestrus in cows. AB - Our hypothesis was that cows with greater body condition at parturition would respond to the presence of bulls (biostimulation) by having shorter periods of postpartum anestrus than cows with a lesser body condition. Multiparous cows in good body condition at the initiation of the study were either maintained on a high dietary regimen or switched to a low dietary regimen during the 90 d preceding parturition. After parturition, half of the cows from each group were placed in pastures with sterile bulls, and the remaining half were placed in pastures without bulls. This study was replicated during a 2nd yr. Blood samples were collected twice weekly and assayed for concentrations of progesterone to estimate time of onset of luteal function after parturition. There was a significant interaction (P less than .05) between body condition at parturition and presence of bulls postpartum on the duration of postpartum anestrus. Cows of lesser body condition that were in the presence of bulls after calving initiated estrous cycles 14 d earlier than cows with lesser body condition that were isolated from bulls. In cows with a greater body condition, presence of bulls after calving only shortened postpartum anestrus by 6 d. Thus, we reject our initial hypothesis. PMID- 1429288 TI - Feeding wash water solids to sows during gestation and lactation: sow productivity, pig performance, and tissue compositions. AB - Diets containing 0, 10, or 20% dried wash water solids (WWS) from a milk processing plant were fed to 54 Yorkshire gilts (160 to 270 kg) for five parities. Feed intake, weight changes, and morbidity of sows were measured; number of pigs per litter, birth weight, and weight gain of pigs were also determined. Blood, tissue, and milk samples were taken from sows for hematological and mineral analyses, and tissue samples were taken from newborn pigs from each treatment per parity. Overall, initial sow weight, sow weight at weaning, and weight losses were not affected (P greater than .05) by treatment. At 107 d of gestation, overall weights decreased (P less than .05) linearly with level of WWS in the diet. The number of pigs per litter and weight of pigs were not affected (P greater than .10) by diet. Concentrations of NA (P less than .10) and Cd (P less than .05) were lower in kidney of sows fed 20% WWS, and concentrations of Zn were lower in bone and in kidney of sows fed the 20% WWS diet. The Sr and Ba concentrations increased (P less than .05, P less than .10) linearly in bone from sows with level of WWS in the diet. In pigs, concentrations of Mn in kidney and Zn in liver were lower for the 20% WWS treatment. In conclusion, feeding WWS to sows over five parities had minimal adverse effects on sow productivity and pig performance; the reduction in Zn concentrations in tissues of sows and pigs seemed to be related to the Ca content of WWS. PMID- 1429290 TI - Growth hormone increases whole-body protein turnover in growing pigs. AB - Ten pigs with an average initial live weight of 65 kg were used to investigate the effects of daily exogenous porcine pituitary growth hormone (pGH; .1 mg.kg 1.d-1) for a 13-d period on N retention and whole-body protein turnover. Feed intake was restricted to both the control (treated with excipient) and pGH treated groups to ensure that animals in each group consumed equal amounts. Whole body protein turnover was estimated from the excretion of 15N in urinary urea and ammonia after a single oral dose of [15N]glycine. Nitrogen balance and whole-body N flux were increased by 35 to 40% with pGH treatment (P less than .001). Protein synthesis and breakdown were increased by 56 and 59% (P less than .001), respectively, in pGH-treated pigs relative to controls. These higher rates of protein turnover seemed to lower slightly the efficiency of the metabolic process for protein deposition. However, the absolute increment in protein synthesis rate was greater than that for breakdown, leading to the increased net N retention. Thus, pGH treatment improved the utilization of dietary amino acids for protein deposition. PMID- 1429291 TI - Regression of induced corpora lutea in mature cyclic gilts by human chorionic gonadotropin. AB - This study was conducted to determine whether chronic hCG treatment would cause regression of induced corpora lutea (CL) in mature cyclic gilts. Thirty-two mature gilts that had displayed one or more estrous cycles of 18 to 22 d were used. Sixteen gilts were hysterectomized (HYSTX) on d 6 to 9 (d 0 = onset of estrus) and their CL were marked with charcoal (spontaneous group). Sixteen gilts (induced group) were injected with 1,500 IU of pregnant mare's serum gonadotropin (PMSG) on d 6 and 500 IU of hCG on d 9 (day of hCG = d 0 of the induced cycle). Ovulation was assumed to occur on d 2 of the induced cycle. Induced gilts were HYSTX on d 8 to 9 (d 17 to 18 of the original spontaneous cycle) and their CL were marked with charcoal. Only gilts (n = 14) in which induced CL were present and in which the original CL had regressed were then subjected to treatment with saline or hCG. From d 10 to 29, gilts with spontaneous CL were injected daily with 500 IU of hCG (n = 8) or saline (n = 8). From d 10 to 29 of the induced cycle, induced gilts were injected daily with 500 IU of hCG (n = 6) or saline (n = 8). Jugular blood samples were collected every other day from all gilts beginning on the 1st d of daily hCG treatment and quantified for estradiol and progesterone by RIA. On the day after the last hCG injection, the number of charcoal-marked CL and charcoal-marked corpora albicantia (CA) were determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429292 TI - Effect of intrauterine bacterial infusions and subsequent endometritis on prostaglandin F2 alpha metabolite concentrations in postpartum beef cows. AB - Multiparous Angus and crossbred Angus cows were used to determine the effect of induced endometritis on plasma concentrations of 13,14-dihydro-15-keto prostaglandin F2 alpha (PGFM) and progesterone (P4) and on duration of the estrous cycle of treatment. Beginning on the day of calving (d 0), blood samples were collected on alternate days. On three consecutive days, ranging from d 8 to 14 of the first postpartum estrous cycle, uterine horns were inoculated transcervically with either 3 x 10(9) colony forming units (cfu) of Actinomyces pyogenes and 1.5 x 10(9) cfu of beta-hemolytic Escherichia coli (treated; n = 9) in sterile PBS or with sterile PBS alone (control; n = 9). Samples of uterine fluid were collected by transcervical aspiration twice weekly from just before the start of each series of inoculations until the end of the experiment. Endometrial biopsies were collected transcervically between d 4 to 6 and 11 to 13 after inoculation. Based on clinical observations and results of bacterial cultures, all treated cows developed acute uterine infections. Controls did not develop uterine infections. Endometrial biopsies indicated that there were no significant diffuse or focal cellular reactions in response to the infection. The interestrous interval was greater (P less than .0003) for treated (27.7 +/- 1.0 d) than for control (20.6 +/- 1.0 d) cows, but P4 concentrations were similar between the two groups. Mean PGFM concentration and PGFM profiles were similar (P greater than .10) between treated and control cows before bacterial infusions. Bacterial infusions increased mean PGFM concentration (P less than .0001) and changed the shape of the PGFM profile (P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429293 TI - Effects of bacterial inoculation of high-moisture ear corn on its aerobic stability, digestion, and utilization for growth by beef steers. AB - High-moisture ear corn (HMEC) was treated with specific bacterial inoculants and evaluated for its aerobic stability and utilization for growth by beef steers. Immediately after harvest, HMEC (65% DM) was ensiled in tower silos after being either untreated (control) or treated with the following inoculants: 1) Ecosyl (E); 2) Ecosyl plus Serratia rubidaea (E + SR); and 3) Ecosyl plus Streptococcus thermophilus (E + ST). A portion of HMEC was frozen immediately (-20 degrees C) and subsequently treated with eight bacterial inoculants before ensiling in laboratory silos; the fermented material was then exposed to air for 7 d for assessment of aerobic deterioration. The eight inoculants included the three used in the tower silos and four additional ones: Streptococcus thermophilus, Bacillus subtilis (BS), Serratia rubidaea, and a mixture of Ecosyl + B. subtilis (E + BS). The growth trial was conducted for 112 d with 32 crossbred steers (average BW 296 kg). A digestion trial was conducted, according to a 4 x 4 Latin square design, using an additional four steers (average BW 367 kg). In both trials, steers were fed the same four diets containing inoculated (E, E + SR, and E + ST) or control HMEC. Upon exposure to air, Ecosyl-treated ensiled HMEC had the least increase in pH compared with other single inoculants; all inoculant treatments lessened (P less than .05) the increase in sample temperature compared with control. During aerobic exposure, treatment of HMEC with BS seemed to reduce the disappearance of water-soluble carbohydrates, whereas Ecosyl seemed to reduce lactic acid. Despite evidence of improved aerobic stability with Ecosyl and BS, inoculation of HMEC did not (P greater than .10) improve BW gain or feed efficiency; however, all inoculants reduced (P less than .05) digestibility of ADF. PMID- 1429294 TI - Effect of intraperitoneal administration of lysine and methionine on mohair yield and quality in Angora goats. AB - Eight mature Angora wethers (average BW 47.2 kg) were used in a 4 x 4 replicated Latin square design to evaluate responses to intraperitoneal (IP) administration of amino acids. The IP treatments consisted of saline (Control), methionine 1 g/d (Met), lysine 2 g/d (Lys), and methionine + lysine (Met + Lys). The amino acids dissolved in Control were infused continuously for the first 14 d of each 28-d period using peristaltic infusion pumps. Average d-28 grease and clean mohair yields (grams/100 square centimeters), and fiber diameter (micrometers) and length (centimeters) measurements during Control administration were 8.8, 7.6, 40, and 2.3, respectively. Mean clean mohair yield and fiber diameter increased by 5.3% (P less than .039) and 2.5% (P less than .067), respectively, with Met administration but were decreased by 9.2% (P less than .033) and 3.8% (P less than .001), respectively, by Lys administration; however, mean fiber length was increased (P less than .014) 21.7% by Lys infusion. The goats did not exhibit increased grease (P greater than .939) and clean (P greater than .477) mohair yields and fiber diameter (P greater than .619) when treated with Met+Lys. A N balance trial was conducted during d 10 through 14 of each period. Total retained N (grams per day) during Control administration was 18.4 and 24% greater than Met (P greater than .281) and Lys (P less than .061), respectively. When expressed as a proportion of N intake, retained N was lowest (P less than .127) in the Lys infusion group. Jugular blood ammonia N and plasma glucose and total protein concentrations were not affected (P greater than .10) by treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429295 TI - Effects of bentonite on wool growth and nitrogen metabolism in fauna-free and faunated sheep. AB - Two experiments were carried out with sheep that originated from a fauna-free flock and were fed a soybean meal-corn silage diet with or without a bentonite supplement. One-half of the sheep fed each diet in each experiment were faunated with a mixed population of ruminal protozoa, whereas the other half of the sheep remained fauna-free until the end of both experiments. Wool growth and daily gain were measured in Exp. 1. (eight rams per treatment), which lasted 110 d, and the metabolic effects in the rumen and intestinal tract of protozoa and dietary bentonite supplement were tested with cannulated wethers (four wethers per treatment) in Exp. 2. The results of Exp. 1 showed decreased wool growth (P less than .05) due to the presence of protozoa in the rumen. Dietary supplementation with bentonite partly offset the decreased wool growth in sheep with protozoa, but there were no effects of dietary bentonite and no protozoa x bentonite interaction (P greater than .05). Daily gain was decreased by the dietary bentonite (P less than .05) supplement but was not affected (P greater than .05) by the ruminal presence of protozoa. In Exp. 2, protozoa increased (P less than .01) the ruminal concentrations of ammonia and decreased (P less than .05) the acetic:propionic acid molar ratio. Fractionation of N in the duodenal digesta flowing from the stomach to the small intestine showed that protozoa decreased (P less than .05) the flow of nonammonia N and bacterial N, and there was a protozoa x bentonite interaction for these effects (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429296 TI - Implant and copper oxide needles for steers grazing Acremonium coenophialum infected tall fescue pastures: effects on grazing and subsequent feedlot performance and serum constituents. AB - Two experiments were conducted to compare the effects of a progesterone-estradiol implant (PEI) with no implant (NI) and 20 g of copper oxide needles (CuON) with no CuON on grazing, subsequent feedlot performance, and selected serum constituents of steers. In Exp. 1, 114 Limousin crossbred yearling steers (317 kg average initial BW) were stocked continuously on Acremonium coenophialum-infected tall fescue (Festuca arundinacea Schreb.)-ladino clover (Trifolium repens L.) pastures (C) or were rotated to bermuda grass (Cynodon dactylon [L.] Pers.) during summer months (R) of two consecutive years. Implant and copper treatments were applied within pasture. Blood samples were collected four times during each grazing season. Continuously stocked steers had greater (P less than .05) grazing gain, less (P less than .10) feedlot gain, and heavier (P less than .05) carcass weights than R steers did. Implanted steers had greater (P less than .05) pasture but lesser (P less than .05) feedlot gains than did NI steers. Prolactin concentrations were greater (P less than .05) from R than from C steers in late summer 1988. Ceruloplasmin was greater (P less than .01) with CuON than without on the last three and last two sampling dates in 1988 and 1989, respectively. In Exp. 2, blood samples were collected twice from 40 mixed-breed steers (283 kg average initial BW) receiving the same implant and copper treatments as in Exp. 1 and grazing infected fescue for one season. Serum ceruloplasmin and copper concentrations were increased (P less than .01) by CuON, but other measurements did not differ among treatments. Summer grazing of bermuda grass increased serum copper, ceruloplasmin, and prolactin but decreased grazing performance. Implanting increased grazing performance. Copper oxide needles increased serum ceruloplasmin and copper concentrations but did not affect steer performance. PMID- 1429297 TI - A computer model to predict empty body weight in cattle from diet and animal characteristics. AB - A computer model was developed to predict empty BW in cattle as a function of diet (forage NDF, physical form of forage [hay vs silage and pasture], proportion of dietary concentrates) and animal (full BW) characteristics. The model was empty BW = full BW * (1 - GFILL), where GFILL is gut fill expressed as a fraction of full BW. An equation obtained from published data (GFILL = .05354 + .329 * NDF) was used to provide a base prediction of GFILL from the fraction of NDF in the forage. Predicted GFILL was then corrected for full BW, physical form of forage, and fraction of concentrates using multiplicative factors obtained from published data. The model was evaluated with data from 11 published experiments. Several breeds of cattle, a wide range of forage types, and diets with 0 to 93% concentrates were represented in these data. Observed values for empty BW were compared to model-predicted values and to values predicted by systems published by the Agricultural Research Council (ARC) and National Research Council (NRC). Sums of squared deviations of predicted values from observed (n = 64) were 3,074, 37,327, and 25,920 for the model, ARC, and NRC systems, respectively. After fitting predicted empty BW values to observed values, proportion of concentrates and forage NDF accounted for a significant (P less than .01) amount of the residual variation with the ARC and NRC systems, but not for the model. This finding suggests that the model will predict empty BW more accurately than the ARC and NRC systems with diets similar to those used in the evaluation. PMID- 1429298 TI - Quantification of intraruminal recycling of microbial nitrogen using nitrogen-15. AB - Studies were done to derive a technique to quantify intraruminal recycling of microbial nonammonia nitrogen (NAN). After dosing 15NH4+ into the rumen, ruminal NH3N and NAN pools were sampled over time for analyses of 15N enrichment. Compartmental analysis of both pools was used to quantify the percentage of microbial NAN that recycles in the rumen. Microbial NAN does not need to be fractionated from total NAN, assuming that only microbial NAN becomes labeled with 15N and that the ratio of microbial NAN:nonmicrobial NAN remains constant over time. Based on the data obtained from eight nonlactating cattle fed 85% corn silage diets at 1.5 to 1.0% BW, percentage of intraruminal recycling of microbial NAN was related to efficiency of bacterial protein synthesis (grams of CP/100 g of OM truly digested) in a curvilinear manner (y = 100 - .073x2). From this function, recycling was predicted to be approximately 75% for dairy cows consuming 50:50 forage:concentrate diets at 3.5% of BW. However, more data are needed to evaluate intraruminal recycling of microbial NAN using this technique under different dietary conditions. PMID- 1429299 TI - Technical note: stocking equivalents and stocking rate-gain relationships for steers and cow-calf pairs grazing oversown bermuda grass. AB - Grazing experiments may use steers or cow-calf pairs for measuring animal performance on pasture treatments, but the validity of extrapolation between these classes of cattle has not been verified. A grazing study was conducted in the spring and summer of both 1988 and 1989 to determine stocking equivalents and stocking rate-weight gain relationships for steers and cow-calf pairs grazing Coastal bermuda grass (Cynodon dactylon [L.] pers.) oversown with rye (Secale cereale L.) and ryegrass (Lolium multiflorum Lam.). Average daily gain and stocking rate (SR; 3.2, 4.2, 6.2, and 7.4 animals per hectare for steers and 1.7, 2.5, 3.7, and 4.9 pairs per hectare for cow-calf pairs) were both adjusted so that comparisons could be made on an equal BW basis. Disk meter height readings were used as measurements of forage accessibility. Disk meter height responses to SR did not differ (P greater than .10) between steer and cow-calf paddocks. There was a linear (P less than .001) decrease in ADG as SR increased, but this decline was steeper (P less than .001) for steers than for cows or suckling calves. Steers tended to be more productive than calves at low SR but less productive at high SR. Disk meter heights for the range of SR used in the study did not differ (P greater than .10) for steers and cow-calf pairs at equivalent BW per hectare. Our study suggests that live BW is a reasonable basis for determining forage requirements of steers and cow-calf pairs under grazing conditions, but extrapolation of production between classes of livestock will not be reliable. PMID- 1429300 TI - Manipulation of amino acid supply to the growing ruminant. AB - Quality of protein (indicated by amino acid [AA] composition) that enters the small intestine (SI) of growing ruminants is dictated largely by the AA composition of microbial protein. The AA supply is well-balanced and, although individual AA can be experimentally determined to be first- or second-limiting, it seems that several AA (sulfur AA, lysine, histidine, and possibly threonine, valine, and isoleucine) may be colimiting in many circumstances. Quality of the postruminal AA supply can be altered by increasing (maximizing) net microbial protein synthesis, manipulating supplemental protein source, or feeding ruminally protected AA. Defaunating the rumen increases postruminal AA supply by increasing flow of both bacterial and nonbacterial AA. Defaunation has little effect on proportions of individual AA entering the SI. Different feed proteins vary greatly in the quantity of individual AA that they supply for absorption from the SI. Most proteins are a poor source of at least one essential AA; feeding combinations of proteins may be the most practical approach to supplying AA in optimal proportions. Feeding individual ruminally protected AA can alter the profile of AA reaching the SI, but work is needed to identify dietary conditions under which use of such products will be most beneficial. PMID- 1429301 TI - Peptide absorption: a review of current concepts and future perspectives. AB - Absorption of di- and tripeptides from the gastrointestinal tract is accepted as being an important biological phenomenon. The extent to which peptides are absorbed and the nutritional and metabolic significance of peptide absorption remain unclear. Evidence is strong for the existence of multiple peptide transport systems, including one type that is electrogenic in nature and that requires a protonmotive force and cotransports two H+ for every peptide transported. The rate of absorption of peptides can be responsive to level of dietary intake and level of dietary protein. Peptide absorption seems to be an important physiological process in ruminants, and this process may account for a large portion of absorbed amino acids. An important new observation is that the nonmesenteric portion of the portal-drained viscera of the ruminant is a major site of peptide absorption. These new observations may result in a reshaping of the currently accepted theory concerning protein utilization by ruminants. PMID- 1429302 TI - New concepts in fetal and placental amino acid metabolism. AB - Fetal amino acid nutrition and metabolism have been studied primarily in pregnant sheep. The umbilical uptake of amino acids changes during gestation, but at both mid- and late gestation the total supply exceeds that required for growth. Weight specific protein synthetic rate decreases with increasing gestational age, and these changes are proportional to the changes in metabolic rate. The use of multiple tracer methodology coupled with measurement of net tracer fluxes into and out of fetal and placental tissues can be used to delineate amino acid metabolism in considerable detail. Such studies demonstrate that even essential amino acids can be oxidized extensively by the fetus. The oxidation rate of leucine exceeds its rate of accretion in tissue proteins. Glycine metabolism is unique in several ways; there is a large umbilical uptake of glycine without a measurable uterine uptake. In late gestation there is no significant umbilical uptake of serine, although there is a significant uterine uptake, suggesting net uteroplacental utilization. Glycine is oxidized within the fetal liver and used for serum production. The interorgan exchange of amino acids between the fetal liver and placenta is clearly of major importance for serine and glycine metabolism and is likely to be of major importance for most nonessential amino acids. PMID- 1429303 TI - Control of the metabolic fate of amino acids in ruminants: a review. AB - In general, ruminants convert ingested feed protein (N) to body tissues with low efficiency (0 to 35%). Although some of this inefficiency is due to the peculiarities of ruminal action and digestion, a large proportion is associated with metabolic events in the tissues. In the fasted condition, amino acid catabolism is greater than in the maintenance-fed animal, and perhaps 40% of this loss is due to provision of carbon sources for gluconeogenesis. The contributions of other pathways to these basal losses are poorly quantified. Below maintenance intake, insulin seems to be a major determinant of the rate of protein loss, primarily through reduction of protein degradation (especially in muscle tissue) with an accompanied decrease in the rate of branched-chain amino acid (BCAA) oxidation. At intakes above maintenance, protein anabolism and amino acid catabolism are more probably regulated by the growth hormone/insulin-like growth factor I (GH/IGF-I) axis, with the major control via alterations in protein synthesis. The actions of insulin and GH/IGF-I may provide overlapping regulatory mechanisms, which would explain the biphasic alterations in protein dynamics and amino acid catabolism observed for the ruminant between the fasted and ad libitum intake conditions. The BCAA may assume a key regulatory role in integrating the metabolism of peripheral tissues with the metabolic and oxidative functions of the liver. This integration seems well-coupled in the ruminant, for which the relationship between the extent of BCAA catabolism in peripheral and hepatic metabolism remains fairly constant under a range of nutritional and physiological conditions. PMID- 1429304 TI - The formation and control of dental plaque--an overview. PMID- 1429305 TI - Prevalence, biotypes, plasmid profile and antimicrobial resistance of Campylobacter isolated from wild and domestic animals from northeast Portugal. AB - The incidence of Campylobacter jejuni and Campylobacter coli in wild and producing animals has been studied to evaluate their importance as potential reservoirs of campylobacter infection. These organisms were isolated from: 59 chicken (60.2%), 65 swine (59.1%), 31 black rats (57.4%), 61 sparrows (45.5%), 21 ducks (40.5%), 32 cows (19.5%) and 27 sheep (15.3%). Biotypes, plasmid and resistance profiles were studied in order to characterize the isolates. Biotypes I and II of C. jejuni were predominant in all reservoirs except swine, where C. coli I was more frequent. Plasmid prevalence was higher in strains isolated from swine (53.8%) and rats (45.5%). The size of the plasmids ranged from 1.3 to 82 MDa. A 2.3 MDa plasmid was the most frequent, detected in all the reservoirs except ducks. Antimicrobial susceptibility testing revealed that 5.5% of the strains were resistant to ampicillin, 5.5% to tetracycline, 12.6% to erythromycin and 23.5% to streptomycin. Resistance to erythromycin (26.2%) and to streptomycin (58.4%) was particularly high in isolates from swine. Tetracycline resistance was encoded by a 33 or a 41 MDa plasmid and transferred by conjugation. PMID- 1429306 TI - Identification and characterization of helveticin V-1829, a bacteriocin produced by Lactobacillus helveticus 1829. AB - Lactobacillus helveticus 1829 produced an antimicrobial agent, designated helveticin V-1829, that demonstrated antagonistic activity against closely related species. The agent was excreted into MRS agar, and was present in the supernatant fluids from both overnight broth and clotted milk cultures. It was heat labile (inactivated by 50 degrees C for 30 min) and was stable over the pH range 2.5 to 6.5. Production of the substance was pH-dependent and maximum yields were obtained in MRS broth cultures maintained at pH 5.5. Helveticin V-1829 was partially purified following growth of the producing strain in a semi-defined MRS medium and precipitating the cell-free filtrate with ammonium sulphate to 30% saturation. The cleared supernatant fluid was then brought to 60% saturation and the resulting precipitate pelleted and dialysed in 0.3 mol/l phosphate buffer. The partially purified inhibitor was sensitive to several proteolytic enzymes, and it was bactericidal in its mode of action against indicator cells of Lact. helveticus 1844 and Lact. delbrueckii subsp. bulgaricus 1489, indicating that it was a bacteriocin. A DNA probe specific for the helveticin J structural gene failed to hybridize to total genomic DNA of Lact. helveticus 1829, indicating that helveticin V-1829 is not significantly related to helveticin J. PMID- 1429307 TI - Isolation and properties of a bacteriocin-producing Carnobacterium piscicola isolated from fish. AB - A facultative psychrotrophic lactic acid bacterium isolated from fresh fish was identified as Carnobacterium piscicola on the basis of carbohydrate utilization, G + C content and 16S RNA analysis. Its bacteriocin, designated carnocin UI49, is produced during the mid-exponential phase of growth at temperatures between 15 degrees C and 34 degrees C. Carnocin UI49 is active against a large number of closely-related lactic acid bacteria including carnobacteria, lactobacilli, pediococci and lactococci. Furthermore, the bacteriocin has a bactericidic mode of action which results in lysis of sensitive cells. Maximum bactericidal activity is observed at 34 degrees C with a decrease in activity down to 15 degrees C where it is completely abolished. PMID- 1429308 TI - Species of Pseudomonas obtained at 7 degrees C and 30 degrees C during aerobic storage of lamb carcasses. AB - A total of 268 strains of Pseudomonas isolated during storage life of lamb carcasses was identified to species level. One-hundred and thirteen strains obtained at 30 degrees C were Ps. fragi (51), Ps. lundensis (17), Ps. fluorescens biovars I (10), III (9) and VI (1), Ps. putida biovar A (8 strains) and unidentified (17 strains). Species and biovars isolated at 7 degrees C (155) were Ps. fragi (101), Ps. lundensis (32), Ps. fluorescens biovar I (6), Ps. putida biovar A (8) and unidentified (8). Numerical analysis (82% SSM, UPGMA) of 'psychrotrophic' and 'mesophilic' strains resulted in the formation of nine and eight clusters respectively. The dendrograms obtained exhibited similar structures. Most of the strains of Ps. lundensis and Ps. fragi clustered together. Strains of this latter species also joined the type strain of Ps. testosteroni and appeared included with phenons containing the Ps. putida strains. There were clusters made up exclusively of strains assigned to one biovar or group (Ps. fluorescens biovars I and II and unidentified). A high level of similarity was observed between clusters of Ps. fluorescens biovar I and those containing the Ps. fragi-Ps. lundensis complex (> 74% SSM) and Ps. lundensis (> 80%). The recovery of pseudomonads seemed to be affected by the sampling day. PMID- 1429309 TI - Incidence of pathogenic bacteria in raw milk in Ireland. AB - Raw milk from 70 farms was sampled over 13 months for salmonellas, listerias, Escherichia coli, Staphylococcus aureus and mastitic streptococci; total bacterial counts (TBC), coliforms and somatic cells were also counted. TBC < or = 30,000/ml were obtained in 63% of samples. High count milks were found mainly during the winter months: 13% of samples had > 10(4) mastitis pathogens/ml of milk. The mean somatic cell count varied from 4.0 x 10(5) to 8.0 x 10(5)/ml throughout the year with highest counts during the late lactation period. Coliforms were present in all samples, but 65-71% of samples had < 100 coliforms/ml. Up to 60% of supplies had < or = 10 E. coli/ml. One of the 589 samples tested (0.1%) was positive for salmonellas. Yersinia enterocolitica and Y. enterocolitica-like organisms were isolated from 39% of samples with up to 68% of samples positive at some sampling periods. A total of 222 strains of yersinias were isolated; Y. enterocolitica (59%) was the most common strain followed by Y. fredriksenii (35%), Y. kristensenii (1.0%), Y. intermedia (4.5%) and Y. aldovae (0.5%). Listerias were isolated from 8.3% of samples tested; 4.9% were Listeria monocytogenes and 3.4% were L. innocua. There was a significant rise in the isolation rate between December and April from a base line of 0-5% during the spring and summer to 35-37% during the winter months while the cows were indoors. Of 66 silage samples tested from the farms involved in the survey 9% of samples were positive for listerias; 3% of these were L. monocytogenes and 6% were L. innocua.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429311 TI - M13 DNA fingerprinting, a new tool for classification and identification of Lactobacillus spp. AB - The optimal conditions for the application of M13 DNA fingerprinting to the genus Lactobacillus were determined. Comparative fingerprint analysis of representative strains of Lactobacillus delbrueckii subsp. delbrueckii, Lact. delbrueckii subsp. lactis, Lact. delbrueckii subsp. bulgaricus, Lact. helveticus and Lact. casei permitted the differentiation of species, subspecies and individual strains and the quantitative determination of their genetic relatedness. The results confirm the high specificity of M13 DNA fingerprinting and indicate that it might be used in the classification of Lactobacillus spp. PMID- 1429310 TI - Comparative study on the antimicrobial effects of Hexomedine and Betadine on the human skin flora. AB - Studies were carried out to detect the modifications, if any, on the peri umbilical flora of six healthy volunteers after two or three daily applications of Hexomedine solution (HEX) and Betadine solution (PVI) repeated for five consecutive days. A standardized scrubbing method was used for bacterial sampling. Surviving bacteria were selected with both selective and non-selective media, and then identified by gas chromatographic fatty acid analysis. Both antiseptics were highly effective, showing both immediate and residual antimicrobial activities. The use of HEX led to a slight increase in Gram positive cocci and a small decrease in coryneforms, but PVI produced a marked increase in Gram-positive cocci and a sharp decrease in coryneforms. The two antiseptics, however, caused no major alteration in the cutaneous microbial population. Indeed, neither the overgrowth of Gram-negative bacilli nor the emergence of resistant species was observed. PMID- 1429312 TI - Study of the bacterial flora of a non-carbonated natural mineral water. AB - Natural mineral water from a UK spring was monitored at various stages after it was pumped from the ground, through to bottling and during shelf life before consumption. Samples were collected in commercial PVC bottles, in PVC bottles previously sterilized and hand-filled and in glass bottles. The bacterial flora was counted on plate count agar (PCA) and on PCA diluted 10 times (PCA/10). The predominant bacteria were identified to genus level. Growth rates and nutrient types of isolates were determined by the nutrient-tolerance test (NT). The plate counts at the pre-bottling stage were low. During storage larger numbers of bacteria grew in glass than PVC bottles; the largest number grew in PVC bottles filled by hand. Most of the pigmented bacteria isolated were oligocarbotolerant. PMID- 1429313 TI - Applying statistical process control to clinical data: an illustration. PMID- 1429314 TI - Ongoing consultation as a method of improving performance of staff members in a group home. AB - A model of ongoing consultation was implemented in a community group home for 8 adults with severe and profound mental retardation. Two consultants, highly experienced in working with people with mental retardation and in the procedures used in group homes, taught staff members to use a token reinforcement system, to engage the adults in a variety of activities, and to improve the content and style of the staff members' interactions with the adults. The consultants taught skills to 9 staff members through brief mini-workshops, direct observation of the staff members' use of the skills during regular activities in the group home, and individual verbal feedback regarding a staff member's performance of the skills. Evaluation of the ongoing consultation process by the 2 consultants showed it to be effective in improving the performance of the staff members and in changing the behaviors of the adults who lived in the home. Continued implementation of the process, however, appeared to be necessary for the behavior changes of staff members to be maintained at high levels. PMID- 1429315 TI - Increasing nurses' use of feedback to promote infection-control practices in a head-injury treatment center. AB - This study established regular implementation of a simple feedback procedure by supervisory nurses with their assistants at a head-injury treatment center. Five nurses were trained to distribute brief written comments to their assistants about infection-control practices, including using gloves to avoid contact with body fluids. Following low rates of written feedback, nurses met with the trainer weekly to set goals for using the system, to review feedback rates, and to examine contingent letters of appreciation. Written feedback increased from 0.09 to 0.58 per day. When outcome data on glove use were subsequently added to the feedback provided to nurses, nurses' feedback on glove use increased and overall glove use by assistants increased by 36.7% for 66.7% of assistants who responded to feedback. Assistants rated feedback as highly accurate and indicated some interest in receiving future feedback. However, nurses and assistants expressed a preference for oral over written feedback. PMID- 1429316 TI - Dentist-implemented contingent escape for management of disruptive child behavior. AB - We evaluated the effectiveness of a dentist-implemented intervention in which brief escape from dental treatment was provided to manage disruptive child behavior during restorative dental treatment. Within a multiple baseline design across subjects, 4 children, aged 3 to 7 years, were provided temporary escape from dental treatment contingent upon brief periods of cooperative behavior. Disruptive behavior decreased when the appropriate escape contingency was used at least 80% of the time. The escape contingency required no more time than traditional management procedures (e.g., tell-show-do, reprimands and loud commands, restraint) to bring disruptive behavior under control. Independent ratings by two dentists provided social validation of the efficacy of the escape contingency. PMID- 1429317 TI - Problem solving to prevent work injuries in supported employment. AB - A problem-solving strategy was used to teach three groups of 3 individuals in supported employment how to prevent work-related injuries. The problem-solving strategy was taught in two training phases. The first training phase involved the use of cue cards, and the second involved the withdrawal of the cue cards. Interviews and staged generalization assessments in the participants' natural work environments were conducted before, during, and up to 12 weeks after training. In these assessments, situations were presented that were either similar or dissimilar to situations presented in training. Results of both the interviews and staged assessments indicated that the participants' newly acquired problem-solving skills generalized to similar and dissimilar situations. PMID- 1429318 TI - Musical reinforcement of practice behaviors among competitive swimmers. AB - This study determined whether music could be used as a reinforcer for increasing productive and decreasing nonproductive behavior of 6 competitive swimmers during the dry-land portion of practice session. The swimmers were randomly assigned to either the contingent reinforcement group, who received music for productive behavior, or the noncontingent group, who received music regardless of their training productivity. An ABAB design showed that a large and immediate increase in productive practice behavior and decrease in nonproductive practice behavior occurred during the contingent phase compared to the baseline phase. Subjects rated the musical reinforcement favorably and elected to have the procedure continued. PMID- 1429319 TI - Effects of a variable-ratio reinforcement schedule with changing criteria on exercise in obese and nonobese boys. AB - The effects of a variable-ratio schedule of reinforcement on pedaling a a stationary exercise bicycle were examined. Three obese and three nonobese 11-year old boys were individually tested five times weekly for approximately 12 weeks. A changing-criterion design was used in which each successive criterion was increased over mean performance rate in the previous phase by approximately 15%. The contingencies of the successive criteria resulted in systematic increases in rate of exercise for all children. Final variable-ratio rates were higher than those under fixed ratios found in previous research, with rates for 2 of the 3 obese boys approximating those of the nonobese. PMID- 1429320 TI - Strategies to increase exercise-report correspondence by boys with moderate mental retardation: collateral changes in intention-exercise correspondence. AB - Correspondence between verbal and nonverbal behavior in an exercise room was taught to 4 13-year-old boys diagnosed with moderate mental retardation. Participants were asked prior to each exercise session which exercise machine(s) they intended to use. No contingencies on stating intentions (promising) were applied. Following the exercise session, participants were asked to say (report) which machine(s) they had used. Following the baseline condition, do-report correspondence training was introduced sequentially across participants. During do-report correspondence training, accurate reporting was reinforced. High rates of both do-report and promise-do correspondence were observed. Data were analyzed via a multiple baseline across subjects design and contingency-space analysis. Results are discussed with regard to observed changes in promise-do correspondence subsequent to observed changes in do-report correspondence. PMID- 1429321 TI - An analysis of a group teaching procedure for persons with developmental disabilities. AB - This study evaluated whether a concurrent group teaching procedure, in which all students respond simultaneously, could be used for persons with moderate or severe mental retardation. The teaching procedure used was the Task Demonstration Model, a program based on stimulus-control research and the fading techniques of behavioral psychology. Three teachers and three groups of students participated. Results showed that the teachers increased their rates of questions and instructions, positive feedback, and use of functional materials, but they reduced their rate of prompts to almost zero. Students increased their percentage and rate of correct responding as well as their engaged time. In addition, maladaptive responding, for which there were never any direct consequences, decreased from 45% to 10% for 8 of the 14 students. Results are discussed primarily in two areas: (a) changing stimulus control from teacher prompts to critical elements of the items being taught, and (b) reasons for the reduction of maladaptive behavior for 8 of the subjects. PMID- 1429322 TI - Brief functional assessment techniques to evaluate aberrant behavior in an outpatient setting: a summary of 79 cases. AB - Previous investigators have analyzed the maintaining conditions for aberrant behaviors using brief functional assessment procedures. These assessment procedures have been used in one of our outpatient clinics, the Self-Injurious and Aggressive Behavior Service. This study presents a descriptive summary of the results from 79 cases during a 3-year period. The outcomes of the brief assessment were evaluated across three variables: (a) referring topography, (b) control over behavior as evaluated through brief multielement designs, and (c) the identified maintaining conditions for aberrant behavior. The limitations and future utility of brief functional assessments for identifying distinct maintaining contingencies are discussed. PMID- 1429323 TI - Effects of a multifaceted training procedure on the acquisition and generalization of social behaviors in language-disabled deaf children. AB - Effects of a multifaceted training procedure were assessed on the acquisition and generalization of social behaviors with 9 language-disabled deaf children. The training procedure consisted of (a) child training and (b) supervision, feedback, and goal setting directed by teachers and residential staff. Target behaviors were turn waiting, initiating interaction, and interacting with others. Procedures to promote generality of effects and to determine the social validity of the procedures were used. Data were collected within a multiple baseline design across behaviors. Results showed a functional relationship between introduction of the training procedure and increases in percentage of appropriate target behaviors for all 9 children. The effects were maintained throughout a 5- to 10-week follow-up period. PMID- 1429324 TI - Covariation within functional response classes: implications for treatment of severe problem behavior. AB - Two studies examined the effects of a reductive treatment versus instruction based treatments on the generalized reduction of problem behaviors. Each study involved a detailed analysis of multiple problem behaviors performed by school aged youth with severe intellectual disabilities. The analysis examined the contrasting effects of one of two different positive intervention procedures (teaching a positive alternative behavior or providing additional teacher assistance during instruction) versus blocking and/or verbally reprimanding a problem behavior. The focus of each analysis was on the covariation of multiple problem behaviors within functional response classes. Results of the investigation indicated that when only one member of the response class was blocked, a collateral increase was observed in one or more different problem behaviors from the same response class. Alternatively, when 1 participant was taught a functionally equivalent mand response, all problem behaviors in the response class were reduced. Problem behaviors also were reduced for the remaining participant by presenting antecedent teacher assistance. Implications of the research extend to analysis of covariation within response classes and to procedures that result in generalized reduction of problem behaviors within a response class. PMID- 1429325 TI - Assessing choice making among children with multiple disabilities. AB - Some learners with multiple disabilities display idiosyncratic gestures that are interpreted as a means of making choices. In the present study, we assessed the validity of idiosyncratic choice-making behaviors of 3 children with multiple disabilities. Opportunities for each child to choose between food and drink were provided under two conditions. In one condition, the children were given the food or drink item corresponding to their prior choice. In the other condition, the teacher delivered the item opposite to that chosen. It was reasoned that valid choice-making behaviors would be reflected in a greater tendency to accept the chosen item and refuse the unchosen item. Direct observations revealed all children consistently indicated choices during both conditions. Choices of both the food and drink items were made by all 3 children. A reversal design demonstrated that acts of refusal were more frequent when choices were followed by delivery of the item opposite to that chosen. Similar assessment procedures may be effective in determining the function of idiosyncratic gestures exhibited by persons with multiple disabilities. For children lacking such skills, intervention to teach valid choice-making behaviors may be needed to complement assessment procedures. PMID- 1429326 TI - Detection of antibiotic resistance genes with DNA probes. PMID- 1429327 TI - Ofloxacin as the standard 4-quinolone in sensitivity tests. PMID- 1429328 TI - Ceftazidime disc content recommendation and susceptibility testing. PMID- 1429329 TI - Detection of glycopeptide resistance in clinical isolates of gram-positive bacteria. PMID- 1429330 TI - Activity of amoxycillin/clavulanic acid against Escherichia coli in vivo- correction. PMID- 1429331 TI - Classification of plasmid-encoded trimethoprim resistance genes. PMID- 1429332 TI - Selection of quinolone-resistant mutants of Haemophilus influenzae and Streptococcus pneumoniae. PMID- 1429333 TI - Faecal carriage of antibiotic-resistant enterococci in hospitalized and non hospitalized individuals. PMID- 1429334 TI - Extended spectrum beta-lactamase from Klebsiella oxytoca, not belonging to the TEM or SHV family. AB - In clinical isolates of Klebsiella oxytoca resistance to cefuroxime and aztreonam was mediated by a beta-lactamase, designated KH, (pI 5.25) which could be transferred into Escherichia coli by electroporation, but not by conjugation. The transformants produced two enzymes with pIs 5.25 and 8.4 respectively, and showed resistance to cefuroxime, aztreonam, cefotaxime and ceftazidime. Substrate and inhibition profiles indicated that KH beta-lactamase was different from TEM- or SHV-like enzymes, but similar to chromosomal K1 beta-lactamase. The enzyme profile with pI 8.4 was similar to the enzyme from the recipient and showed elevated activity in transformants. The plasmid profiles of the transformants were different from those of their donors. However, a plasmid fragment of the K. oxytoca isolate KH11 hybridized with a plasmid ranging in size from 4.8 to 7.8 kilobases in all the transformants and most of the donors. Gene probes encoding TEM-1 or SHV-1 did not hybridize with plasmid DNA from the K. oxytoca isolates. Furthermore, a probe of the ampC gene did not hybridize with the plasmid but to DNA fragments of the same size in whole cell DNA preparations from the E. coli XAC recipient and the TKH11 transformants. This indicates that no gross rearrangements in the chromosomal beta-lactamase gene region had occurred in the transformants which could explain the increased expression of the pI 8.4 beta lactamase. PMID- 1429335 TI - In-vitro activity of ten antimicrobial agents against penicillin-resistant Streptococcus pneumoniae. AB - The minimum inhibitory concentrations (MICs) of ten antibiotics were determined by the agar dilution method for 40 strains of penicillin-resistant Streptococcus pneumoniae, all of which were clinical isolates from this laboratory. The antibiotics tested were clarithromycin, erythromycin, teicoplanin, vancomycin, ceftriaxone, cefodizime, azithromycin, ramoplanin, ciprofloxacin and MDL 62873. Of these agents, clarithromycin, vancomycin, teicoplanin, ceftriaxone, ramoplanin and MDL 62873 were the most active. The role of these antibiotics as alternatives to penicillin for the treatment of infections caused by penicillin-resistant S. pneumoniae is discussed. PMID- 1429336 TI - The antimicrobial susceptibility of Moraxella catarrhalis isolated in England and Scotland in 1991. AB - Between 1 January and 31 March 1991, 20 laboratories in England and Scotland sent a total of 413 consecutive clinical isolates of Moraxella catarrhalis to The London Hospital Medical College (LHMC). After confirmation of identity, the susceptibility of all isolates to 11 antimicrobial agents was determined. Of the 375 (90.8%) isolates which were found at LHMC to be beta-lactamase-positive, 174 produced zones of inhibition around 2 micrograms ampicillin disc which were greater than or equal to 20 mm in diameter and 252 were inhibited by less than or equal to 0.5 mg/L of ampicillin. However, 71 of these 375 had been reported to be ampicillin-susceptible by peripheral centres. While beta-lactamase had not been detected in 35 of these 71 isolates, the other 36 had been reported to be ampicillin-susceptible and beta-lactamase-positive. All 38 beta-lactamase negative isolates produced zones greater than or equal to 30 mm in diameter and were inhibited by less than or equal to 0.06 mg/L of ampicillin. No M. catarrhalis isolate was found to be resistant to co-amoxiclav, tetracycline, chloramphenicol or cefaclor. Two strains showed intermediate susceptibility to erythromycin (MIC 1 mg/L) and 27 required greater than or equal to 32 mg/L of sulphamethoxazole for inhibition. Resistance to trimethoprim was uniform (MICs 2 128 mg/L). Two isolates showed intermediate susceptibility to cefixime (MIC 2 mg/L) but none was resistant to the new oral cephalosporin cefetamet or to the oral carbacephem loracarbef.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429337 TI - Effects of cefaclor, cefetamet and Ro 40-6890 on inflammatory responses of human granulocytes. AB - The effect of three cephalosporins (cefetamet, cefaclor and Ro 40-6890) upon human granulocytes and their ability to modulate the chemiluminescence response, phagocytose, kill bacteria and generate leukotrienes was studied. In the presence of the cephalosporins there was a significant increase in phagocytosis of Escherichia coli. The bactericidal activity of human granulocytes for several other bacteria was also enhanced. Cefetamet and cefaclor increased the chemiluminescence response of human neutrophils to Pseudomonas aeruginosa and Proteus mirabilis in contrast to Ro 40-68790, which decreased the chemiluminescence response. The cephalosporins decreased the synthesis of leukotrienes from human neutrophils after stimulation with Escherichia coli and Staphylococcus aureus. These data emphasize the immunomodulatory functions of various cephalosporins on cells involved in host defence. PMID- 1429338 TI - Concentrations of cefpodoxime in serum and bronchial mucosal biopsies. AB - Cefpodoxime proxetil is a new orally administered cephalosporin which has a favorable spectrum of activity against respiratory pathogens. Concentrations of cefpodoxime in serum and bronchial mucosal biopsy were measured in 13 patients without active respiratory tract infection undergoing fibreoptic bronchoscopy. Samples were taken between 1 and 6 h after a single oral dose of cefpodoxime proxetil equivalent to 200 mg of cefpodoxime base. In twelve patients who completed the study, mean serum concentrations were 1.7 mg/L (S.E.M. 0.4) and in ten patients mean bronchial biopsy concentrations were 0.9 mg/L (S.E.M. 0.2). The mean penetration was 54% (S.E.M. 6.1). Cefpodoxime was undetectable in biopsies from two patients. The majority of serum and biopsy concentrations were in excess of the MIC90S for Haemophilus influenzae and Streptococcus pneumoniae. Cefpodoxime proxetil may be worthy of further study in clinical trials in patients with respiratory infections. PMID- 1429339 TI - A controlled trial of selective decontamination of the digestive tract in intensive care and its effect on nosocomial infection. AB - Nosocomial infection is a major problem in intensive therapy units (ITUs) and a significant cause of mortality. Selective decontamination of the digestive tract (SDD) has been advocated as a means to reduce ITU morbidity and mortality. Ninety one patients in a general ITU underwent SDD, consisting of topical polymyxin E, tobramycin and amphotericin B administered throughout the unit stay together with parenteral ceftazidime for the first three days, and were compared with 84 historical and 92 contemporaneous control patients who were treated conventionally. Twenty-seven historical and 32 contemporaneous control patients developed unit-acquired infections, in comparison with only three patients in the SDD group (P less than 0.01). Mortality in the SDD group (36%) was not significantly different from that in the other two groups (historical control 40%, contemporaneous control 43%). Screening specimens revealed a significantly higher rate of colonization with resistant Acinetobacter spp. in the contemporaneous control than in the other two groups of patients; infection caused by resistant bacteria did not occur. SDD did not lead to a significant reduction in the use of systemically-administered antibiotics when compared with either control group. SDD may be used selectively in an ITU without ill effects on those patients not receiving SDD; nevertheless, microbiological monitoring is needed to detect emergence of resistant bacteria in the unit. PMID- 1429340 TI - Hematopoietic growth factors. AB - Recent advances in our understanding of the hemolymphopoietic growth factors has revolutionized knowledge of blood cell development, the immune system, and of tumor cell biology. However, the rapid translation of these insights from basic research to the clinic has been perhaps the most dramatic part of the story. Commercially available erythropoietin has become established for the treatment of the anemia of end-stage renal disease, and promises to be of value in the supportive care of patients with cancer and perhaps other chronic diseases. It likely will be increasingly utilized for enhancing autologous blood donation and for perioperative management. Both GM-CSF and G-CSF only recently released by the FDA for specific clinical indications, though there are a variety of potential applications (Table 12). It is clear that G-CSF is the therapy of choice for most neutropenias and that both agents have effects in diminishing the myelotoxicity and mucositis seen after aggressive chemoradiotherapy. However, it is important to note that as yet there is no evidence that the use of either G-CSF or GM-CSF has resulted in increased cure rates or, in fact, increased survival in patients with various malignancies. It would appear that both G-CSF and GM-CSF will, in fact, allow dose escalation and/or diminished toxicity of various chemotherapeutic regimens. However, there are important considerations in the overall place of these cytokines with regard to treatment of human disease. A major goal in the therapy of patients with malignancy is obviously prolongation of life and cure. If, in fact, escalation of doses of chemotherapeutic agents does not result in increased tumor responses or cures then the use of these growth factors will have a relatively trivial impact on the care of cancer patients. In addition, the disturbing observations of receptors for these growth factors on various tumor cell lines and of varying degrees of in vitro tumor cell proliferative responses raises the possibility that in some situations they may actually stimulate tumor growth. This is an unknown which has not been adequately evaluated in any clinical study to date and which may vary from tumor to tumor. For example, if these cytokines increase tumor growth rate by 20-30% (an effect which would probably not be detected in the clinical studies to date) while allowing an escalation of chemotherapy doses it is possible that there would be no significant beneficial effect.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1429341 TI - T-cell activation-associated antigen expression by neoplastic T-cells. AB - In this study, a clinicopathologically and immunophenotypically diverse group of T-cell neoplasms were evaluated by one- and two-color flow cytometry and/or immunohistochemistry for the presence of eight antigens (T10, T9, IL2-R, EMA, HLA DR, LeuM1, Ki-1, and LeuM5) which are expressed in a hierarchical manner by phytohemagglutinin (PHA)-activated benign T cells. We found that 70 of the 72 T cell neoplasms (97%) expressed at least one of these eight T-cell activation associated antigens (T-AAgs) and that the number and type of T-AAgs expressed by the neoplastic T cells varied according to the clinicopathologic category of T cell neoplasia. All 5 T-cell lymphoblastic malignancies expressed T10 and T9; 2 also expressed LeuM1. Twelve of 14 (86%) T cell chronic lymphocytic leukemias (T CLL) expressed two to four T-AAgs, most frequently T10 (86%) and HLA-DR (79%). The 26 cutaneous T-cell lymphomas (CTCL) expressed between 2 and 5 T-AAgs, most commonly T9 (92%) and HLA-DR (92%), and least often T10 (12%) and EMA (15%). Twenty-six of 27 (96%) peripheral T-cell lymphomas (PTCL) expressed more than 4 T AAgs. Each of the T-AAgs were expressed by between 22% (LeuM5) and 85% (T9) of the PTCLs. Some T-AAgs were preferentially expressed by the PTCLs in association with other T-AAgs, such as EMA in association with IL2-R and Ki-1. In addition, LeuM5 was preferentially expressed by CD4- CD8+ T-cell neoplasms. However, only 19 of the 72 (26%) T-cell neoplasms (3/5 lymphoblastic malignancies, 3/14 CLLs, 0/26 CTCLs, 13/27 PTCLs) expressed T-AAg immunophenotypic profiles paralleling those expressed by normal peripheral blood T cells activated in vitro with PHA. These results suggest that T-AAg expression by neoplastic T cells does not often mirror the hierarchical order of expression by activated benign T cells, implying that neoplastic T cells do not usually represent the precise malignant counterpart of activated benign, normal T cells. PMID- 1429342 TI - In vitro study of erythropoiesis in patients with aplastic anemia and myelodysplastic syndromes: a possible tool for prospective determination of the clinical effectiveness of growth factors. AB - Effects of recombinant human erythropoietin (rhEpo) and the combination of recombinant human interleukin-3 (rhIL-3) or recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) with rhEpo on erythroid colony formation were examined in vitro in 13 patients with aplastic anemia and 16 with myelodysplastic syndromes (MDS). The methylcellulose cultures of marrow cells from normals and the patients yielded no erythroid colonies in the absence of rhEpo. In normals, CFU-E and BFU-E colony formation was significantly increased by adding either rhIL-3 or rhGM-CSF with rhEpo, compared with rhEpo alone, and rhIL-3 was more potent than rhGM-CSF to form colony-forming units and burst forming units of erythroid (CFU-E) (BFU-E) colonies. By adding rhIL-3 with rhEpo, CFU-E colony formation was increased in half of patients with RA, compared with rhEpo alone, and by rhGM-CSF, in one third. Approximately one third or one fourth of the patients with MDS showed increased BFU-E colonies when rhIL-3 or rhGM-CSF were added to rhEpo. Cultures containing rhIL-3 or rhGM-CSF with rhEpo yielded larger numbers of BFU-E colonies in half of the patients with nonsevere aplastic anemia than those containing rhEpo alone. These observations suggest that the combination of these growth factors, especially rhIL-3 with rhEpo, is applicable to the treatment of anemia in some patients with aplastic anemia and MDS. PMID- 1429343 TI - Primary splenic presentation of plasma cell dyscrasia: report of two cases. AB - Primary splenic presentation of plasma cell tumors is extremely rare. Recently we observed two female patients with primary (initially solitary) plasmacytoma of the spleen. While the pathoanatomical diagnosis of plasmacytoma could be established easily, the clinical picture in both cases was puzzling and allowed no definitive diagnosis to be made. One of the patients exhibited a long-standing monoclonal gammopathy. Repeated bone marrow examinations in both patients revealed slight increase in plasma cells (between 5 and 10% of all nucleated cells), but no infiltrates of multiple myeloma. The leading clinical feature in both cases was pronounced splenomegaly (780 g and 1600 g). Histologically both spleens exhibited marked infiltration by pleomorphic plasma cells, with monotypic expression of IgG kappa in one case and of the light chain lambda in the other. A broad panel of monoclonal antibodies detecting various hemopoietic and nonhemopoietic antigens was used to determine the immunophenotype of the neoplastic plasma cells, but in both cases they reacted only with a minority of the antibodies applied. The bone marrow in both cases remained free of tumorous infiltrates, but the disease progressed a few months after splenectomy with infiltration of the liver in one case and of lymph nodes in the other. To summarize, these two cases are definitely not multiple myelomas but could represent a distinct entity among the plasma cell dyscrasias for which the preliminary term "disseminated plasmacytoma with primary splenic presentation" is proposed. PMID- 1429344 TI - Trisomy 4: clinical picture, hematology, and survival. Presentation of two cases and review of the literature. AB - Two patients with acute nonlymphocytic leukemia (ANLL) and trisomy 4 as the only cytogenetic aberration are presented. Including the two, a total of 31 cases with this karyotype have been described till now. A review of the 31 cases shows that they fall into two distinct age groups, a younger group of 10 patients (5-34 years) and an older group of 21 patients (50-75 years). With four exceptions the diagnosis was ANLL in all cases, mostly FAB classes M2 and M4. At the time of diagnosis 18 had clinical signs of active infection. In 20 cases the peripheral leukocyte count was above 10 x 10(9)/L but not associated with presence/absence of infection. The median survival was 17 months from diagnosis. Independent prognostic factors were diagnosis (p = 0.01), peripheral leukocyte count (p = 0.03), and percentage of metaphases with trisomy 4 (p = 0.04). The two age groups as well as presence/absence of infection at the time of diagnosis were without significant prognostic consequences. PMID- 1429345 TI - Predicting individual differences in complex skill acquisition: dynamics of ability determinants. AB - Substantial controversy exists about ability determinants of individual differences in performance during and subsequent to skill acquisition. This investigation addresses the controversy. An information-processing examination of ability-performance relations during complex task acquisition is described. Included are ability testing (including general, reasoning, spatial, perceptual speed, and perceptual/psychomotor abilities) and skill acquisition over practice on the terminal radar approach controller simulation. Results validate and extend Ackerman's (1988) theory of cognitive ability determinants of individual differences in skill acquisition. Benefits of ability component and task component analyses over global analyses of ability-skill relations are demonstrated. Implications are discussed for selection instruments to predict air traffic controller success and for other tasks with inconsistent information processing demands. PMID- 1429346 TI - The meaning of occupational stress items to survey respondents. AB - This study tested the effect of using the word stress in the measurement of self reported occupational stressors and strains. Employees from two organizations responded to a questionnaire that included specific occupational stressors, strains, and 16 items in which the word stress was used. Survey respondents tended to interpret the word stress to refer both to employees' strains or reactions to the work environment and to job stressors or elements of the environment itself. Implications of these findings for occupational stress research are discussed. PMID- 1429347 TI - The effects of goal difficulty on physiological arousal, cognition, and task performance. AB - Two laboratory experiments with 117 undergraduate students were conducted to examine (a) the effect of assigned goal difficulty on arousal (self-report and heart rate), cognition (perceived norm, self-efficacy strength, and personal goal), and behavioral (task performance) measures and (b) the role of heart rate as a mediator of the goal-difficulty-performance relation. All Ss performed a task requiring cognitive and physical responses. Results of both experiments demonstrated that assigned goal difficulty affected heart rate, cognition, and task performance and that heart-rate change was positively related to the cognitive and behavioral measures. Regression analyses suggested that a cognitive affective mechanism may mediate the goal-difficulty-performance relation. Discussion is focused on the theoretical and practical implications of integrating an arousal concept within goal-setting theory. PMID- 1429348 TI - Detection measures in real-life criminal guilty knowledge tests. AB - The present study provides a first attempt to compare the validity of the respiration line length (RLL) and skin resistance response (SRR) amplitude in real-life criminal guilty knowledge tests (GKTs). GKT records of 40 innocent and 40 guilty Ss, for whom actual truth was established by confession, were assessed for their accuracy. When a predefined decision rule was used and inconclusive decisions were excluded, 97.4% of the innocent Ss and 53.3% of the guilty Ss were correctly classified with the SRR measure. For the RLL measure, the respective results were 97.2% and 53.1%. The combination of both measures improved detection of guilty Ss to 75.8% and decreased detection of innocent Ss to 94.1%. The combined measure seems to be a more useful means of identifying guilty suspects than each physiological measure alone. The results elaborate and extend those obtained in a previous field study conducted by Elaad (1990). PMID- 1429349 TI - Subliminal self-help audiotapes: a search for placebo effects. AB - Subliminal self-help audiotapes to aid weight loss were evaluated to determine if their apparent effectiveness is due to a placebo effect. All subjects were female students or staff who were both overweight and believed in the possible effectiveness of subliminal audiotapes. Three different groups of subjects were tested: One group listened to subliminal audiotapes purchased directly from a manufacturer, the 2nd group listened to comparable placebo tapes, and the 3rd group did not listen to any tapes at all. Each subject in each group was weighed once each week for 5 weeks. All 3 groups of subjects lost weight, and the average amount of weight lost by each group was approximately equivalent. These results provide no evidence that regular use of subliminal audiotapes leads to a placebo effect. Rather, the results suggest that regular use of subliminal audiotapes may simply make subjects more conscious of their weight. PMID- 1429350 TI - Modulation of the growth and morphology of a human nasopharyngeal carcinoma cell line by growth factors. PMID- 1429351 TI - Test system for human tumor cell sensitivity to drugs on chicken chorioallantoic membranes. PMID- 1429352 TI - New embryonic cell line from Aedes krombeini (H.) (Diptera:Culicidae) PMID- 1429354 TI - Snake venom platelet inhibitor (rhodostomin) inhibits cell-attachment. PMID- 1429353 TI - Fate of antibody-neocarzinostatin conjugates bound to human colonic carcinoma cells in vitro. PMID- 1429355 TI - Long-term passage of human tissues in vitro as three-dimensional histolines. PMID- 1429356 TI - A new side-by-side diffusion cell for studying transport across epithelial cell monolayers. PMID- 1429357 TI - TGF-beta does not appear to mediate all effects of 12-O-tetradecanoylphorbol-13 acetate on the anchorage-independent growth of murine epithelial JB6 cells. PMID- 1429358 TI - Is melatonin really an in vitro inhibitor of human breast cancer cell proliferation? PMID- 1429359 TI - Glucose consumption end point in primary histoculture indicates recovery of human tumors from drug treatment. PMID- 1429360 TI - Protein profiles of embryonic, adult and transformed frog kidney cells. PMID- 1429361 TI - Cells, lines and DNA fingerprinting. PMID- 1429362 TI - Optimization of estrogen growth response in MCF-7 cells. AB - The factors involved in estradiol-17 beta induced growth stimulation of MCF-7 human breast cancer cells have been examined. Wild type MCF-7 cells (and clone E3) were shown to undergo slow growth in phenol-red-free medium containing specific calf sera. The E3 clone was used to document a mean 6-day growth stimulation of 3.35-fold (doubling time = 33 +/- 3 h) in cultures supplemented with 10(-11) M estradiol-17 beta. The serum batch utilized in the culture medium is most important in acquiring significant growth stimulation of MCF-7 cells by estradiol-17 beta. Regardless of the absence of phenol-red, only selected sera (2 out of 14 tested) supported minimal growth of MCF-7 cells in the absence of added estradiol 17 beta (doubling time = 55 +/- 11 h). When a calf-serum-supplemented culture failed to display a complete growth response to estradiol-17 beta, it was due to the rapid growth of the cells in the control (minus estradiol-17 beta) flasks. Sera that promoted shorter doubling times for MCF-7 cells cultured in the absence of estradiol-17 beta were rendered less supportive of growth if treated with dextran-coated charcoal or when cultures were supplemented with the estrogen antagonist ICI 164,384 (10(-7) M). Pooled extracts of these sera were shown to contain stimulatory levels of estradiol-17 beta. Dextran-coated charcoal treatment of sera removed or deactivated factors (other than estradiol-17 beta) which were not only required for the growth of MCF-7 cells, but were necessary for estrogen-stimulated growth. Varying the serum-containing medium, buffer, and nutrient mix or the addition of insulin has no effect on the growth response of these cells to estradiol-17 beta. These investigations document the culture conditions required to produce a maximal and consistent proliferative effect of E2 on MCF-7 cells without exposing the serum constituent to damaging chemical or absorbent agents. PMID- 1429363 TI - Isolation and long-term maintenance of differentiated adult chicken hepatocytes in primary culture. AB - Adult chicken hepatocytes were obtained by an adaptation of the two step in situ collagenase perfusion. Usually 0.5 to 1 x 10(9) cells were obtained, with 75 to 95% viability. Hepatocytes attached within 2 h when plated on plastic cell culture dishes and spread in 4 h, surviving for several months in a specific serum-free medium. These cells retained a typical parenchymal cell morphology and the ability to produce a specific protein (albumin) throughout the culture period. We hereby provide a suitable model for studying hepatic metabolism in birds. PMID- 1429364 TI - Nerve growth factor binding sites on hepatic parenchymal cells. AB - Nerve growth factor (NGF) binding sites on rat hepatocytes (HCs) in culture for 24 to 48 h were characterized using 125I-NGF. Specific binding of 125I-NGF to HCs was saturable. Scatchard analysis indicated a single population of binding sites with a Kd of 5.5 nM and a Bmax of 540 fmol/mg protein. In isolated hepatocyte membranes, specific binding of 125I-NGF was also apparent with Kd and Bmax values of 10.8 nM and 3740 fmol/mg protein, respectively. Specific binding of 125I-NGF to HCs was displaced by excess, unlabeled NGF but not by up to 1000-fold excess of either insulin or epidermal growth factor. Internalization/sequestration of 125I-NGF into HCs was measured as radioactivity present in solubilized cells after exposure to high salt and acid. These studies indicated 83 +/- 11% of 125I NGF was accumulated by internalization/sequestration at a concentration of 1 nM 125I-NGF. Internalization was reduced to 43 +/- 4% when incubations were carried out at 4 degrees C. These results indicate the presence of a specific, low affinity binding site for NGF on hepatocytes in culture. PMID- 1429365 TI - Hormonal induction of functional differentiation and mammary-derived growth inhibitor expression in cultured mouse mammary gland explants. AB - A method for the cultivation of organ explants from abdominal mammary glands of virgin mice has been established. In a serum-free medium containing aldosterone, prolactin, insulin, and cortisol (APIH medium) mammary gland development was documented by lobuloalveolar morphogenesis. The hormonal requirements for in vitro expression of beta-casein and of the mammary-derived growth inhibitor (MDGI) were tested. To this end, a full length cDNA coding for mouse MDGI was prepared displaying strong homologies to a mouse heart fatty acid binding protein, which is also expressed in the mammary gland. MDGI and beta-casein transcripts were found to be absent in the mammary tissue from primed virgin mice, and were induced upon culture of mammary explants in the APIH medium. An immunohistochemical analysis with specific antibodies against MDGI and casein revealed a different pattern of expression for the two proteins. In the APIH medium, MDGI was expressed mainly in differentiating alveolar cells of the lobuloalveolar structures, whereas beta-casein was present in both ductules and alveoli. The relationship between functional differentiation and MDGI expression was further studied in explants from glands of late-pregnant mice. At this stage of development, MDGI is found both in ducts and in alveoli. If explants were cultured with epidermal growth factor (EGF) and insulin, the lobuloalveolar structure was still present, whereas MDGI disappeared. Reinduction of MDGI expression was achieved by subsequent PIH treatment. Independent on developmental stage, EGF strongly inhibits MDGI mRNA expression. It is concluded that MDGI expression is associated with functional differentiation in the normal gland. PMID- 1429366 TI - Antioxidant enzymes in the differentiated Caco-2 cell line. AB - Injury to the gastrointestinal tract by oxygen dependent processes is important in ischemia, inflammatory bowel disease, and necrotizing enterocolitis. The Caco 2 cell line is an important tool in assessing various gastrointestinal functions and offers a unique opportunity to assess gastrointestinal oxidant metabolism on a cellular level. However, some Caco-2 cell functions change with time after confluence. To determine if antioxidant enzyme activity changes during differentiation, Caco-2 cells were grown to confluence, and superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities and specific mRNA content were quantitated. With time after confluence the enzymes demonstrated a small, but statistically significant increase in activity. Neither superoxide dismutase nor glutathione peroxidase mRNA levels correlated with enzyme activity changes. Catalase mRNA levels increased as catalase activity increased. Thus, differentiated Caco-2 cells express superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities and the superoxide dismutase, glutathione peroxidase, and catalase genes. Superoxide dismutase activity and glutathione peroxidase activity do not correlate with mRNA levels, and suggest that regulation may be at a level other than transcription. The correlation between catalase activity and catalase mRNA suggests differentiation may occur at transcription. If Caco-2 cells are used to elucidate oxidative metabolism, changes in activities of antioxidant enzymes as a function of cell differentiation should be considered. PMID- 1429367 TI - Two unique human leukemic T-cell lines endowed with a stable cytotoxic function and a different spectrum of target reactivity analysis and modulation of their lytic mechanisms. AB - We have reported the establishment of two interleukin (IL)-2-dependent human leukemic cell lines (TALL-103/2 [CD3+TCR gamma delta +] and TALL-104 [CD3+ TCR alpha beta +]) which display major histocompatibility complex nonrestricted tumoricidal activity. Whereas TALL-103/2 cells lyse only natural killer cell susceptible targets, TALL-104 cells display a broad range of tumor target reactivity. In reverse antibody-dependent cell-mediated cytotoxicity (ADCC), lysis by both cell lines is triggered by monoclonal antibodies (mAb) recognizing CD3 and, to a lesser extent, CD2, but not CD8 or CD56 antigens. In conventional cytotoxic assays, the lytic activity of both cell lines is strictly Ca(2+) dependent. In reverse ADCC, lysis by TALL-103/2 cells is highly dependent on the presence of Ca2+, whereas TALL-104 cells seem to only partially require extracellular Ca2+. The cytoplasm of both cell lines contains azurophilic granules typical of cytotoxic cells. Northern blot analysis demonstrates mRNA expression of pore-forming protein (PFP; perforin) and serine esterases (SE). The magnitude of expression of these transcripts and of lytic activity depends on the doses of IL-2. Upon deprivation of IL-2, TALL-103/2 cells completely lose cytotoxic granules and function within 16 h, whereas TALL-104 cells progressively lose expression of PFP and SE mRNA, as well as killer activity, within 4 wk. Both anti-CD3 mAb and lysable target cells induce efficient BLT-esterase secretion from TALL-103/2 and TALL-104 cells analogous to findings with conventional cytotoxic T lymphocytes. The stable expression of tumoricidal activity over 2 yr in culture renders these cell lines unique and very useful for studies on the regulation of cell-mediated lysis in vitro and in animal models. PMID- 1429368 TI - Inducible expression of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interferon-gamma in two human cytotoxic leukemic T cell lines. AB - We investigated the ability of the TALL-103/2 and TALL-104 leukemic cell lines to produce lymphokines in response to activation signals, such as tumor cells and anti-CD3 (OKT3) or -CD2 (B67.1) monoclonal antibodies (mAb) or both. Both cell lines were found to produce high levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and granulocyte-macrophage colony-stimulating factor (GM CSF). The latter lymphokine is induced by lysable tumor cells and by immobilized OKT3 and B67.1 mAb only in the presence of interleukin (IL-2). IFN-gamma and TNF alpha are induced upon CD3 but not CD2 stimulation, both in the presence and absence of IL-2. Interestingly, the B67.1 mAb amplifies the OKT3-induced responses by 2- to 10-fold, bringing the IFN-gamma and TNF-alpha levels of production up to 200 U/ml. Thus, simultaneous triggering of the CD2 and CD3 signaling pathways results in a very efficient lymphokine release. Of all the tumor cell lines tested as inducers, only K562 cells are able to stimulate the production of IFN-gamma and TNF-alpha in TALL-103/2 and TALL-104 cells, especially upon culture in IL-2. Lymphokine mRNA expression after stimulation with mAb or K562 cells peaks at 2 h in both cell lines. No messages are detectable in TALL-103/2 cells at 8 h, whereas in TALL-104 cells, IFN-gamma and GM-CSF transcripts are still present at 8 and 20 h, respectively. The inducible and highly regulatable expression of lymphokine release by these cell lines provides a unique model for studying mechanisms of lymphokine induction by different biological agents. PMID- 1429369 TI - Phospholipids regulate growth and function of MDCK cells in hormonally defined serum free medium. AB - The effects of the simple phospholipids phosphatidic acid (PA) and lysophosphatidic acid (LPA) on the growth and function of Madin Darby Canine Kidney (MDCK) cells has been studied. We observed that PA and LPA not only stimulated the growth of MDCK cells (at 20 microM), but also stimulated the growth of normal rabbit kidney cells in serum free medium (albeit at a lower dosage of 5 microM). Evidence was obtained that PA interacts synergistically with insulin so as to elicit a growth stimulatory effect. Recently, extracellular PA and LPA were proposed to stimulate mitogenesis in several types of animal cells by binding to particular sites on the plasma membrane which are coupled to signaling mechanisms such as adenylate cyclase via a pertussis toxin sensitive, inhibitory guanosine triphosphate binding protein (Gi protein) (15). However, even when the pertussis toxin dosage was increased to 50 ng/ml, LPA still had a dramatic growth stimulatory effect on MDCK cells. In the absence of LPA pertussis toxin was slightly growth stimulatory to MDCK cells. Phospholipids such as PA and LPA have been observed to prevent prostaglandin-induced increases in adenylate cyclase activity in other cell types via their effects on such a pertussis toxin sensitive Gi protein. If PA and LPA act on MDCK cells in this manner, then these phospholipids may possibly prevent the effect of PGE1 on the growth of normal MDCK cells. However PGE1 was still growth stimulatory to normal MDCK cells. The effects of PA on PGE1 independent variants of MDCK cells, which have elevated intracellular cyclic AMP levels (22), were also examined. In the presence of PA, PGE1 remained growth inhibitory, rather than growth stimulatory to the PGE1 independent cells. However, the PA dosage required to elicit an optimal growth response (5 microM) was dramatically reduced, as compared with normal MDCK cells (20 microM). This altered dosage requirement could be explained by the elevated intracellular cyclic AMP levels in the PGE1 independent variants. Like PGE1 and 8 bromocyclic AMP, PA and LPA also significantly increased the initial rate of Rb+ uptake by confluent monolayers of MDCK cells. The increase in the initial rate of Rb+ uptake could be explained by an increase in the ouabain-sensitive component of Rb+ uptake. An increase in the initial rate of ouabain-insensitive Rb+ uptake was also observed in LPA treated MDCK cell cultures. PMID- 1429370 TI - RB tumor suppressor gene expression responds to DNA synthesis inhibitors. AB - Expression of the RB tumor suppressor gene, whose function is putatively in controlling cell growth, may be regulated by S-phase specific inhibitors of DNA synthesis that are commonly used in cell synchronization and cancer chemotherapy. Relatively low concentrations of the agents, cytosine arabinoside, bromodeoxyuridine, 5-fluorouracil, hydroxyurea, methotrexate and retinoic acid, were tested. At low concentrations still permitting submaximal cell growth, these drugs all changed RB gene expression, causing either up or down regulation of RB expression to varying degrees. Despite their potential similarity as a class, the nucleotide analogues elicited differential effects. The drug-induced up or down regulation of RB expression did not correlate with changes in c-myc expression indicating that the changes are not a manifestation of general metabolic changes potentially associated with altered proliferation. Amongst the agents considered, retinoic acid was the only one that caused a significant parallel reduction in RB and c-myc expression in the HL-60 human promyelocytic leukemia cells tested. The results thus show that even low concentrations of DNA synthesis inhibitors can have unpredictable affects on expression of growth regulatory genes. PMID- 1429372 TI - Government and other regulations of clinical practice. PMID- 1429371 TI - A simplified method for the culturing of primary adult rat and human hepatocytes as multicellular spheroids. AB - A simple and highly reproducible method was established for the culturing of adult rat and human hepatocytes as multicellular aggregates (spheroids). Purified rat and human liver parenchymal cells were cultured on nontissue culture (bacteriological) polystyrene petri dishes on a rotating platform. After an overnight incubation, the cells were found to form multicellular aggregates. The aggregates became spheroidal in shape after several days in culture. Histological sections of the spheroids showed an organized structure consisting of squamated cells on the outermost layer and cuboidal cells in the interior. Cellular structures characteristic of hepatocytes in the liver in vivo including bile canaliculi, peroxisomes, Golgi bodies, abundant mitochondria, and rough and smooth endoplasmic reticulum were observed with electron microscopy. The spheroids were found to be viable up to the longest time studied of approx. 1 month in culture as demonstrated by their adherence and growth on collagen-coated substratum. The morphological resemblance between hepatocytes cultured as spheroids and the liver in vivo suggests that the spheroids may be a useful in vitro experimental model of the liver. Our simple method should allow hepatocytes to be cultured as spheroids easily in any laboratory equipped for cell culture. Our study here also is the first to report the culturing of human hepatocytes as spheroids. PMID- 1429373 TI - The senior physicians of Arkansas: a decade (almost!) in review. PMID- 1429375 TI - Arkansas Medical Society. New members. PMID- 1429374 TI - Arkansas HIV/AIDS report 1983-1992. PMID- 1429376 TI - Electrocardiogram of the month. PMID- 1429377 TI - Radiological case of the month. Small bowel obstruction--patient A. Adynamic ileus--patient B. PMID- 1429378 TI - TTL auto flash--Part 1: Calibration and compensation for close-up photography. PMID- 1429379 TI - "Gene in the bottle". PMID- 1429380 TI - A photographic apparatus designed to save time and labor. 1933. PMID- 1429382 TI - Colored lantern slides of photomicrographs from a single negative.1933. PMID- 1429381 TI - The reversal of 16 mm. positive film or movies for approximately a cent and one half per foot.1933. PMID- 1429383 TI - The invisible photographic screen.1933. PMID- 1429384 TI - The development of photographic chemistry.1933. PMID- 1429385 TI - Nicholas M. Graver receives Louis Schmidt Award. PMID- 1429386 TI - Understanding computer viruses. PMID- 1429387 TI - High resolution electronic imaging of the human body. PMID- 1429388 TI - Comments on the untoward effects of corticosteroids on the musculoskeletal system. PMID- 1429389 TI - The untoward effects of steroid treatment on the musculoskeletal system and what to do about them. AB - The focus of this review is the musculoskeletal side effects of corticosteroids. These untoward effects can be divided into high-dose phenomena (myopathy and aseptic necrosis) and low-dose problems (growth suppression and osteoporosis). For the clinician, the former group may be an uncommon experience whereas the latter group is highly predictable. The low-dose problems are subtle and asymptomatic, and they can occur in spite of alternate day dosing with steroids. Treatments available to prevent or treat these side effects in patients who are unable to discontinue steroids are reviewed. PMID- 1429390 TI - Airway response to inhaled fenoterol in hyperthyroid patients before and after treatment. AB - Bronchodilatory response to inhaled fenoterol was studied in 15 hyperthyroid patients before and after successful treatment with antithyroid drugs. Baseline forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) were lower than the predicted values in 12 and 11 patients, respectively. Improved values were seen after treatment for hyperthyroidism although statistical significance was not reached. Even if some improvement occurred in PEFR (a rise by 0.24-0.48 L/s) and FVC (increase of 73-78 ml) in the hyperthyroid state in response to fenoterol inhalation after various time intervals, the increase in different parameters of lung function was significantly more after the patients achieved euthyroid state (increases in FVC by 290-165 ml; in FEV1 by 333-193 ml; in peak expiratory flow (PEFR) by 0.75-0.52 L/s and in forced expiratory flow (FEF50%) by 0.55-0.31 L/s). In the euthyroid state the mean absolute improvements from the baseline values were significantly higher (< 0.05-0.001). These observations indicate that bronchodilatory response is impaired in the presence of excess thyroid hormones and improves after euthyroid state is achieved. PMID- 1429392 TI - House-dust mite allergy and eosinophilia in patients with asthma in Rangoon (Yangon). AB - Skin tests were done by prick and intradermal techniques, using house dust mite (Dermatophagoides pteronyssinus) antigen on 35 patients with early onset asthma, 33 with late onset asthma, 43 with asthma and frequent cough with sputum production (chronic bronchitis) and 30 control subjects. Absolute blood eosinophil and sputum eosinophil (as percentage of leukocytes) counts were performed on each patient. Positive skin tests to house dust mite antigens were significantly more frequent in each of the patient groups (35-75%) than in control subjects (0%), but were not significantly different among the three groups of asthmatics. All three groups of asthmatics had significantly higher mean blood absolute eosinophil counts and sputum eosinophil counts than control subjects, eosinophilia being most frequent in patients with early onset asthma. These findings suggest the importance of exposure to house dust mite antigens in the development of asthma in patients in Rangoon (Yangon), Burma (Myanmar). PMID- 1429391 TI - Airway responses to repeated exercises detected by krypton-81m in asthmatic children. AB - A repeated exercise program was used to test 7 asthmatic children for changes in ventilation. These changes were examined by continuously inhaled Krypton-81m and compared in subjects with positive and negative refractoriness, as defined by forced expiratory volume in 1 second (FEV1). Three of the seven patients showed significant refractoriness (% reduction in FEV1 > 50%). After the first exercise, they showed one or two ventilation defects which improved after the second exercise. The patient with incomplete refractoriness showed similar results. On the contrary, subjects without refractoriness showed several ventilation defects which fluctuated after the second or third exercise program. One defected area improved after the second exercise session, but deteriorated after the third; and another area deteriorated after the second exercise and improved after the third. It was concluded that approximately half of the patients were refractory in view of FEV1, but that they were all refractory in view of regional ventilation 81mKr images. PMID- 1429393 TI - A life activities questionnaire for adult asthma. AB - The development, testing, and applicability of an instrument, the Life Activities Questionnaire for Adult Asthma is described that can be used to assess activity restriction in adults with asthma. It explains how items for the instrument were selected to insure the validity of the developed instrument. The reliability of the questionnaire is also discussed. The result is a valid and reliable paper-and pencil instrument that should have wide applicability as a component of quality of life measurement. This instrument has potential for functional use in clinical settings, research environments, and policy-making procedures. PMID- 1429394 TI - A protocol for aerosol therapy in acute hospitalized asthmatics. AB - The most important element in the treatment of acute hospitalized asthmatics is salbutamol administered via wet nebulization prescribed usually on a subjective evaluation of the patient's status. This study outlines a novel protocol that incorporates the FEV1 variable as the major objective parameter in a feedback loop. Data from patients admitted in the year prior to the initiation of the protocol (N = 348) were compared with similar data from patients hospitalized the year following institution of the protocol (N = 238). There were no withdrawals from the protocol due to adverse effects nor were there any deteriorations requiring ICU admission. A significant decrease in the length of hospitalization and the number of salbutamol prescriptions per hospitalization was observed after, relative to before, institution of the protocol (2.2 vs. 2.6 days; 2.3 vs. 3.8; p < .05, respectively). It is concluded that this protocol is safe and efficient, and may also be more efficacious than a nonstandardized approach for treating the hospitalized asthmatic child. PMID- 1429395 TI - A mediastinal tumor in an asthmatic boy. PMID- 1429396 TI - Debunking the myths of adolescence: findings from recent research. AB - This review summarizes some of the important research findings on adolescence that have accumulated during the past two decades. Current understanding of the adolescent age-period is first discussed with particular attention to the previously held myths about adolescence. Second, a review of existing studies that have examined the problems and help-seeking behaviors of adolescents is presented. Overall, the majority of recent research findings suggest adolescence should not be characterized as a time of severe emotional upheaval and turmoil because the majority (80%) of adolescents manage this transition quite well. Nevertheless, a sizable proportion of youth (20%) do not fare so well, with many not receiving the help they may need. PMID- 1429397 TI - Children, adolescents, and substance abuse. Introduction. PMID- 1429398 TI - Hospitalized children of substance-abusing parents and physically and sexually abused children: a comparison. AB - The symptoms and diagnoses of 58 psychiatrically hospitalized children aged 12 or under who were children of substance abusing parents (COSAPs) were compared with a matched group of 51 children who were not COSAPs. These two groups were further subdivided according to history or lack of history of physical and/or sexual abuse. Symptoms and diagnoses of COSAPs and physically and/or sexually abused (P/SAs) children differed significantly from the hospitalized group who were neither COSAPs nor P/SAs. Being a COSAP and/or P/SA are strong correlates of psychiatric hospitalization for the children studied. Both high-risk groups should be awarded special diagnostic and treatment consideration that would include their systematic identification and focused treatment. PMID- 1429399 TI - Childhood psychopathology in families with multigenerational alcoholism. AB - The present study examined psychopathology in high-risk children (ages 8 to 18) from families with a multigenerational history of alcoholism and contrasted them with low-risk children from community control families. Similar rates of childhood disorders were found for the high- and low-risk groups whether or not the children lived with an alcoholic parent. These findings suggest that the increased psychopathology commonly reported for children of alcoholics arises from comorbidity within the extended family as a result of assortative mating. When comorbidity is reduced through the selection of families with only alcoholism, a different symptom picture emerges. PMID- 1429400 TI - Characteristics of adolescent psychiatric patients who engage in problematic behavior while intoxicated. AB - Although many adolescent psychiatric patients drink and use drugs, not all engage in problematic behaviors or experience social difficulties while intoxicated. The goal of this study was to identify characteristics of adolescent psychiatric patients for whom intoxication leads to behavioral, social, and medical problems. Alcohol-involved adolescent psychiatric inpatients were divided into high and low problem severity groups and compared on a number of measures. The groups did not differ in alcohol or drug consumption or psychiatric diagnoses. High problem severity was primarily associated with drinking in response to unpleasant affect and the belief that alcohol enhances social behavior. Explanations for the results are discussed, along with clinical implications. PMID- 1429401 TI - Psychiatric disorders in substance-abusing adolescent inpatients: a pilot study. AB - In a pilot study of 226 adolescents entering inpatient treatment because of a primary substance use disorder, 82% met DSM-III-R criteria for an Axis I psychiatric disorder. Of this population, 74% had two or more psychiatric disorders. Mood disorders were found in 61%, conduct disorders in 54%, and anxiety disorders in 43%. Substance induced organic mental disorders were found in 16%. The data argue strongly for the simultaneous evaluation of both substance use and psychiatric disorders in this type of adolescent population. The pilot study also demonstrates the relative frequency of dually diagnosed subgroups. The authors propose that the dual diagnosis subgrouping may have specific treatment implications involving a combined psychiatric and substance abuse treatment approach. PMID- 1429402 TI - Patterns of affective comorbidity in a clinical population of dually diagnosed adolescent substance abusers. AB - Patterns of affective comorbidity with substance abuse are examined in a sample of 156 adolescent psychiatric inpatients, ages 13 to 18 years old. Affective disorders, including adjustment disorder with depressed mood, were observed in 51.3% of patients. A total of 30.7% of patients had comorbid major depression. In both males and females, secondary major depressive disorder was more common than its primary form. In this population, the primary-secondary paradigm did not predict either acute remission for depressive symptoms or distinct family history of comorbid disorders. Consistent with previous studies of adults, significantly more females had comorbid affective disorder and significantly more males had conduct disorder. PMID- 1429403 TI - Comparison between treatment completers and noncompleters among dually diagnosed substance-abusing adolescents. AB - The psychiatric and demographic characteristics that may distinguish treatment completers from noncompleters among hospitalized adolescents with substance abuse and comorbid psychiatric disorders were examined. Affective and adjustment disorders were more prevalent among treatment completers whereas non-completers were more likely to be assigned a conduct disorder diagnosis. There were no differences between the groups with respect to demographic and legal status, education level and lifetime psychiatric diagnosis in the parents or caretakers, living arrangements, treatment history, and perception of treatment benefits. A higher percentage of treatment completers than noncompleters received psychotropic medications. The factors contributing to treatment termination as well as the clinical and research implications of the findings are discussed. PMID- 1429404 TI - Obsessions and compulsions across time in 79 children and adolescents with obsessive-compulsive disorder. AB - Individual symptoms of 79 children and adolescents with severe obsessive compulsive disorder were obtained from chart review of at least two in-persons evaluations and recorded across an average of 7.9 years (range, 2 to 16). Symptoms were grouped according to the categories of the Yale-Brown Symptom Checklist. No significant age related trends were found with any one type of symptom, although patients with a very early onset of illness (less than 6 years old) were more likely to have compulsions than obsessions. Across the study period, patients reported symptoms from many different symptom categories, with 47% of the patients displaying both washing and checking compulsions at some time during their illness. No patient maintained the same constellation of symptoms from presentation to follow-up. These data support the concept of obsessive compulsive disorder as an illness with varied clinical manifestations that individually change over time. PMID- 1429405 TI - An epidemiological study of obsessive-compulsive disorder and related disorders in Israeli adolescents. AB - Five hundred and sixty-two, 16- to 17-year-old consecutive inductees into the Israeli Army, constituting a random sample of their cohort, were screened for obsessive-compulsive disorder (OCD), Tourette's syndrome, transient tics (TT), chronic multiple tics (CMT), and attention-deficit hyperactive disorder (ADHD). Two child psychiatrists interviewed the subjects, using screening items from structured interviews that implement DSM-III-R diagnostic criteria. For OCD, a point prevalence of 3.6% was found, 3.9% for ADHD, 1.8% for CMT, and 1.6% for TT. For ADHD, TT, and CMT, but not for OCD, there was a significantly higher prevalence for males than for females. Among the OCD individuals, there was an elevation of TT, CMT, and Tourette's syndrome relative to the population rates. PMID- 1429407 TI - DSM-III-R anxiety disorders in children: sociodemographic and clinical characteristics. AB - This study investigated the characteristics of each of the specific DSM-III-R (American Psychiatric Association, 1987) anxiety disorders in a clinic sample of 188 anxiety disordered children. Characteristics examined included sociodemographic variables (age-at-intake, gender, and race of the child, and family marital and socioeconomic status) and clinical variables (disorder age-at onset and severity, and history of additional disorders). Findings are discussed in light of the contemporary literature on childhood anxiety disorders. PMID- 1429408 TI - Clinical phenomenology of child and adolescent dissociative disorders. AB - A comparison of two separately diagnosed samples of children and adolescents with dissociative disorders demonstrates good construct validity for these diagnoses in childhood. Descriptive analyses of the total sample reveal a clinical profile characterized by a plethora of affective, anxiety, conduct, posttraumatic, and dissociative symptoms. Children with multiple personality disorder (MPD) differ from those with dissociative disorder not otherwise specified (DDNOS) in having more amnesias, identity disturbances, and hallucinations. Adolescents were more symptomatic than children age 11 or younger and more likely to receive a diagnosis of multiple personality disorder. PMID- 1429406 TI - Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder. AB - Rigorously designed clinical trials have demonstrated the efficacy and safety of fluoxetine in adults with major depressive disorder and obsessive-compulsive disorder (OCD) but not in patients below 18 years old. This report describes a randomized, double-blind, placebo-controlled, fixed-dose (20 mg qd) trial of fluoxetine in 14 children and adolescents with OCD, ages 8 to 15 years old; the study was 20 weeks long with crossover at 8 weeks. Obsessive-compulsive symptom severity was measured on the Children's Yale-Brown Obsessive Compulsive Scale (CY BOCS) and the Clinician's Global Impression-Obsessive Compulsive Disorder scale (CGI-OCD). The CY-BOCS total score decreased 44% (N = 7, p = .003) after the initial 8 weeks of fluoxetine treatment, compared with a 27% decrease (N = 6, p = .13) after placebo. During the initial 8 weeks, the magnitude of improvement for the fluoxetine group significantly exceeded that for the placebo group as measured by the CGI-OCD (p = .01) but not by the CY-BOCS (p = .17). The most common drug side effects were generally well tolerated. The results suggest that fluoxetine is a generally safe and effective short-term treatment for children with OCD. PMID- 1429409 TI - Avoidant disorder and social phobia in children and adolescents. AB - The diagnoses of avoidant disorder and social phobia in children have received little research attention. Although DSM-III-R describes avoidant disorder and social phobia as data are available to support this notion. The current study examined characteristics of avoidant disorder and social phobia by comparing outpatient youngsters with avoidant disorder, social phobia, and avoidant disorder plus social phobia on demographic variables and patterns of comorbidity. The psychiatric groups were compared with matched normal controls on symptom measures of depression and fear. Findings indicated that the three psychiatric groups were strikingly similar on all but one variable, age at intake. These findings question the notion of avoidant disorder and social phobia as distinct disorders in children and adolescents. PMID- 1429410 TI - An integrated medical and psychiatric approach to conversion symptoms in a four year-old. AB - Conversion disorder is a challenging diagnosis in children and adolescents. Medical and psychiatric diagnoses need to be evaluated both separately and in relation to each other. This case highlights both the diagnostic criteria for a conversion disorder in a young child and the need for an integrated medical and psychiatric approach by physicians. PMID- 1429411 TI - Buspirone-associated mental status changes. AB - The pharmacological management of anxiety in children primarily has used antidepressants, such as imipramine. Buspirone, an atypical anxiolytic, has been shown to be of benefit in both adults and children. It has relatively few side effects and is generally well tolerated. Two cases are reported here involving children treated for anxiety with buspirone who subsequently suffered a possible psychotic deterioration. PMID- 1429412 TI - Recruitment and training of child and adolescent psychiatry residents from pediatrics. AB - This article describes a 21-year experience of recruiting and training child and adolescent psychiatry residents with pediatric backgrounds. Three grounds of physicians are compared: those with previous training in general psychiatry alone, those with previous training in both general psychiatry and pediatrics, and those with previous training in pediatrics alone. Residents with pediatric backgrounds compared favorably with those with general psychiatry training. Those with only pediatric training were not only able to successfully complete the residency, but also the majority entered the field of child psychiatry. The findings support accepting residents directly from pediatrics as a viable pathway into child psychiatry. PMID- 1429413 TI - Screening for psychosocial dysfunction in inner-city children: further validation of the Pediatric Symptom checklist. AB - A sample of 123 6- to 12-year-old outpatients at an inner-city pediatric clinic was screened for psychosocial dysfunction using the Pediatric Symptom Checklist (PSC), a brief parent-completed questionnaire. The prevalence of positive screening scores on the PSC was 22%, significantly higher than the rate found in lower middle to upper middle-class samples. Comparing PSC case classifications with comprehensive assessments made by clinicians, overall agreement was 92% (kappa = 0.82; sensitivity = 88%; specificity = 100%); a comparison with several other measures provided additional support for the validity of the PSC. The PSC's reliability over time was also acceptable. These findings provide preliminary evidence that the PSC is as valid and reliable for screening children from economically disadvantaged and minority backgrounds as it is for middle and upper middle-class populations. PMID- 1429414 TI - Prevalence and predictors of pervasive noncompliance with medical treatment among youths with insulin-dependent diabetes mellitus. AB - School-age children were assessed longitudinally for up to 9 years, after the onset of their insulin-dependent diabetes mellitus (IDDM), to determine the time dependent risk of the psychiatric diagnosis of noncompliance with medical treatment and to examine protective and risk factors. The cumulative risk for this diagnosis over the 9 years was .45. Noncompliance tended to emerge in middle adolescence and was found to be protracted. Social competence, self-esteem, and aspects of family functioning at IDDM onset and initial psychiatric status did not predict noncompliance. However, noncompliance was associated with having major psychiatric disorder later in the course of IDDM. PMID- 1429415 TI - Depressive symptoms and adaptive style in children with cancer. AB - OBJECTIVE: This article explores the relationship between a repressive style of adaptation and depressive symptomatology. METHODS: Thirty-one adolescent cancer patients were compared with 83 healthy high school students. Subjects with repressive adaptation were identified as those reporting low anxiety and high defensiveness. Depressive symptomatology was measured by self-report. RESULTS: Patients with cancer reported significantly lower levels of depression, and a significantly higher proportion were identified as repressors. Repressor status accounted for significant variance in depression over that explained by illness. CONCLUSIONS: Adaptive style may be common in medically ill children and may directly and indirectly influence psychological and medical outcome. PMID- 1429416 TI - Profiles, correlates, and trajectories of intelligence in Prader-Willi syndrome. AB - Three aspects of intellectual functioning in persons with Prader-Willi syndrome were examined in two, related studies. In study 1, 21 subjects were evaluated with a psychometric instrument that assesses neuropsychological styles of cognitive processing, the Kaufman Assessment Battery for Children. Prader-Willi subjects showed deficits in sequential processing, and strengths in academic achievement tasks such as reading and vocabulary. In contrast to previous reports on the syndrome, no relationship was found between weight and degree of intellectual impairment. Study 2 included a cross-sectional examination of the trajectory of IQ in 21 subjects aged 13 to 46 years, as well as a longitudinal analysis of 31 subjects aged 5 to 30 years who were tested twice with the same IQ test. No evidence of the previously described decline in IQ over time was noted in either the cross-sectional or longitudinal analyses. The implications of these findings for interventions are discussed. PMID- 1429417 TI - Adaptive and maladaptive behavior in Prader-Willi syndrome. AB - The development and profiles of adaptive and maladaptive behavior of 21 adolescents and adults with Prader-Willi syndrome were cross-sectionally examined with the Vineland Adaptive Behavior Scales and Achenbach's Child Behavior Checklist (CBCL). Adaptive strengths emerged for the group as a whole in daily living skills, and this strength became more pronounced with increasing age. A relative weakness was found in socialization, most notably in coping skills. CBCL findings indicated that externalizing behaviors were particularly heightened in adolescence and that many behaviors previously described as either emerging or worsening in adolescence also persist into the adult years (e.g., temper tantrums, arguing, irritability, stubbornness, lying, skin picking, obsessions, defiance). Certain elevated CBCL behaviors were unique to young versus old age groups, and aging in this syndrome may be associated with heightened confusion, withdrawal, and fatigue. The need to study adaptive and maladaptive features in a wider age range of subjects with Prader-Willi syndrome was emphasized. PMID- 1429418 TI - Psychopharmacogenetic aspects of Prader-Willi syndrome. AB - The study of genes, drugs, and behavior in three male adolescents with Prader Willi syndrome (PWS) revealed a clinical profile that raises questions about the indications for neuroleptic and appetite-suppressing medications in this condition. Evidence of the inadvisability of neuroleptic medication and of the pathophysiology of PWS has led to a remarkable control of violent outbursts and hyperphagia by carbamazepine in one patient afflicted with both PWS and Klinefelter's syndrome. Testosterone and behavioral therapy proved to be useful in the management of two patients. The present observations, which are supported by recent advances in the pathophysiology of satiety, suggest that PWS should be understood as a metabolic disorder and subjected to psychopharmacogenetic study. PMID- 1429419 TI - Specific frontal lobe deficits among women with the fragile X gene. AB - The neurocognitive phenotype of fragile X and its relation to cytogenetic expression were examined among 10 fragile X women with > or = 2% expression, 10 0% obligate carriers, and 10 controls. Measures were obtained for intellectual ability, achievement, and verbal, nonverbal, memory, and frontal lobe functions. Results show that no group demonstrated deficits on verbal, nonverbal, or memory measures. In contrast, when controlling for effects of IQ, the expressing fragile X women exhibited (1) deficits on measures of frontal lobe functioning, and (2) enhanced performance on verbal, but not figural, memory. Frontal lobe deficits may account for behavioral and cognitive manifestations of fragile X. PMID- 1429420 TI - Clomipramine treatment of stereotypic behaviors and self-injury in patients with developmental disabilities. AB - The authors report an open clinical trial of clomipramine for chronic stereotypic and self-injurious behaviors in 11 consecutive patients with concomitant developmental disorders. Ten patients (91%) had marked decreases in rates of target behaviors. No seizures occurred despite the inclusion of six patients with previous histories of epileptic events, and improvement was evident regardless of level of mental retardation. These findings support both the clinical use of serotonergic medications in this population and the need for further research. PMID- 1429421 TI - Neuroleptic-induced catatonia as a stage in the progression toward neuroleptic malignant syndrome. AB - Neuroleptic-induced catatonia is reported in an adolescent patient who responded successfully to lorazepam. The authors propose five discrete stages toward the progression of neuroleptic malignant syndrome, each with a separate treatment. PMID- 1429422 TI - Hyperactivity and attention deficit disorder syndromes in China. PMID- 1429423 TI - AACAP parameters of practice: reinforcers or bribes? PMID- 1429424 TI - Growth deficits and desipramine. PMID- 1429425 TI - Mania and anticonvulsant therapy. PMID- 1429426 TI - Clomipramine side effects. PMID- 1429427 TI - Clozapine for refractory psychosis. PMID- 1429428 TI - A bulimia family survey. PMID- 1429429 TI - Neglect of Asperger's syndrome. PMID- 1429430 TI - Diversity among clinical isolates of Histoplasma capsulatum detected by polymerase chain reaction with arbitrary primers. AB - Clinical isolates of the fungal respiratory and systemic pathogen Histoplasma capsulatum have been placed in several different classes by using genomic restriction fragment length polymorphisms (RFLPs), but in general have not been distinguished further. We report here that a polymerase chain reaction (PCR) based DNA fingerprinting method that has been termed arbitrary primer or random amplified polymorphic DNA (RAPD) PCR can distinguish among isolates in a single RFLP class. In this method, arbitrarily chosen oligonucleotides are used to prime DNA synthesis from genomic sites that they fortuitously match, or almost match, to generate strain-specific arrays of DNA fragments. Each of 29 isolates of RFLP class 2, the group endemic in the American Midwest, was distinguished by using just three arbitrary primers. In contrast, laboratory-derived S and E colony morphology variants of two strains were not distinguished from their R parents by using 18 such primers. Thus, the clinical isolates of H. capsulatum are quite diverse, but their genomes remain stable during laboratory culture. These outcomes suggest new possibilities for epidemiological analysis and studies of fungal populations in infected hosts. PMID- 1429431 TI - Clostridium sticklandii glycine reductase selenoprotein A gene: cloning, sequencing, and expression in Escherichia coli. AB - Gene grdA, which encodes selenoprotein A of the glycine reductase complex from Clostridium sticklandii, was identified and characterized. This gene encodes a protein of 158 amino acids with a calculated M(r) of 17,142. The known sequence of 15 amino acids around the selenocysteine residue and the known carboxy terminus of the protein are correctly predicted by the nucleotide sequence. An opal termination codon (TGA) corresponding to the location of the single selenocysteine residue in the polypeptide was found in frame at position 130. The C. sticklandii grdA gene was inserted behind the tac promotor of an Escherichia coli expression vector. An E. coli strain transformed with this vector produced an 18-kDa polypeptide that was not detected in extracts of nontransformed cells. Affinity-purified anti-C. sticklandii selenoprotein A immunoglobulin G reacted specifically with this polypeptide, which was indistinguishable from authentic C. sticklandii selenoprotein A by immunological analysis. Addition of the purified expressed protein to glycine reductase protein components B and C reconstituted the active glycine reductase complex. Although synthesis of enzymically active protein A depended on the presence of selenium in the growth medium, formation of immunologically reactive protein did not. Moreover, synthesis of enzymically active protein in a transformed E. coli selD mutant strain indicated that there is a nonspecific mechanism of selenocysteine incorporation. These findings imply that mRNA secondary structures of C. sticklandii grdA are not functional for UGA directed selenocysteine insertion in the E. coli expression system. PMID- 1429432 TI - Mutants carrying conditionally lethal mutations in outer membrane genes omsA and firA (ssc) are phenotypically similar, and omsA is allelic to firA. AB - We have previously identified the gene (the ssc gene) defective in the thermosensitive and antibiotic-supersusceptible outer membrane permeability mutant SS-C of Salmonella typhimurium and shown that this gene is analogous to the Escherichia coli gene firA (L. Hirvas, P. Koski, and M. Vaara, EMBO J. 10:1017-1023, 1991). Others have tentatively implicated firA in a different function, mRNA synthesis. Here we report that the defect in the thermosensitive outer membrane omsA mutant of E. coli (T. Tsuruoka, M. Ito, S. Tomioka, A. Hirata, and M. Matsuhashi, J. Bacteriol. 170:5229-5235, 1988) is due to a mutation in firA; this mutation changed codon 271 from serine to asparagine. The omsA-induced phenotype was completely reverted by plasmids containing wild-type firA or ssc. Plasmids carrying the omsA allele, or an identical mutant allele prepared by localized mutagenesis, under the control of lac elicited partial complementation. Transcomplementation studies with plasmids carrying various mutant alleles of the S. typhimurium gene indicated that the ability of these plasmids to complement the omsA mutation was similar to their ability to complement the ssc mutation. The antibiotic-supersusceptible phenotype of the omsA mutant closely resembled that of the ssc mutant, i.e., the omsA mutant was supersusceptible to hydrophobic antibiotics and large-peptide antibiotics against which the intact outer membrane is an effective permeability barrier. As previously demonstrated with the omsA mutant, the outer membrane of the ssc mutant became selectively ruptured after incubation for 1 h at the growth nonpermitting temperature; 82% of the periplasmic beta-lactamase and less than 3% of the cytoplasmic marker enzyme were released into the medium. All of these findings are consistent with our concept that firA is an essential gene involved in generation of the outer membrane. PMID- 1429433 TI - Regulation of narK gene expression in Escherichia coli in response to anaerobiosis, nitrate, iron, and molybdenum. AB - The regulation of the narK gene in Escherichia coli was studied by constructing narK-lacZ gene and operon fusions and analyzing their expression in various mutant strains in response to changes in cell growth conditions. Expression of narK-lacZ was induced 110-fold by a shift to anaerobic growth and a further 8 fold by the presence of nitrate. The fnr gene product mediates this anaerobic response, while nitrate control is mediated by the narL, narX, and narQ gene products. The narX and narQ gene products were shown to sense nitrate independently of one another and could each activate narK expression in a NarL dependent manner. We provide the first evidence that NarL and FNR interact to ensure optimal expression of narK. IHF and Fis proteins are also required for full activation of narK expression, and their roles in DNA bending are discussed. Finally, the availability of molybdate and iron ions is necessary for optimal narK expression, whereas the availability of nitrite is not. Although the role of the narK gene product in cell metabolism remains uncertain, the pattern of narK gene expression is consistent with a proposed role of NarK in nitrate uptake by the cell for nitrate-linked electron transport. PMID- 1429435 TI - Repression of Escherichia coli purB is by a transcriptional roadblock mechanism. AB - Escherichia coli purB is regulated by a repressor-operator interaction. The purB operator is 242 bp downstream from the transcription start site and overlaps condons 62 to 67 in the protein-coding sequence (B. He, J. M. Smith, and H. Zalkin, J. Bacteriol. 174:130-136, 1992). The mechanism by which the repressor operator interaction functions to repress transcription was investigated by a combination of promoter replacement experiments and RNA analyses. By using a trp promoter replacement that deleted 5' flanking DNA to position -986, purB expression was increased sevenfold, yet normal two- to threefold regulation was maintained. This indicates that repressor-operator control is independent of the purB promoter and other 5' flanking sequences. Transcriptional regulation was likewise independent of coupled translation. An approximately 260-nucleotide truncated in vivo purB mRNA was identified which was dependent upon repressor operator interaction. Thus, binding of purine repressor to the purB operator inhibits transcription elongation by a roadblock mechanism. The roadblock was not influenced by a sevenfold increase in promoter strength or by an operator mutation resulting in a 2.5-fold increase in repressor-operator affinity. PMID- 1429434 TI - Phenol hydroxylase from Trichosporon cutaneum: gene cloning, sequence analysis, and functional expression in Escherichia coli. AB - A cDNA clone encoding phenol hydroxylase from the soil yeast Trichosporon cutaneum was isolated and characterized. The clone was identified by hybridization screening of a bacteriophage lambda ZAP-based cDNA library with an oligonucleotide probe which corresponded to the N-terminal amino acid sequence of the purified enzyme. The cDNA encodes a protein consisting of 664 amino acids. Amino acid sequences of a number of peptides obtained by Edman degradation of various cleavage products of the purified enzyme were identified in the cDNA derived sequence. The phenol hydroxylase cDNA was expressed in Escherichia coli to yield high levels of active enzyme. The E. coli-derived phenol hydroxylase is very similar to the T. cutaneum enzyme with respect to the range of substrates acted upon, inhibition by excess phenol, and the order of magnitude of kinetic parameters in the overall reaction. Southern blot analysis revealed the presence of phenol hydroxylase gene-related sequences in a number of T. cutaneum and Trichosporon beigelii strains and in Cryptococcus elinovii but not in Trichosporon pullulans, Trichosporon penicillatum, or Candida tropicalis. PMID- 1429436 TI - Formation of the LuxR protein in the Vibrio fischeri lux system is controlled by HtpR through the GroESL proteins. AB - The transcription of the luminescence (lux) system of Vibrio fischeri is regulated by the LuxR protein and an autoinducer. We previously showed that apart from these regulatory elements, the transcription of the lux system is negatively controlled by the LexA protein and positively controlled by the HtpR protein (sigma 32). This study was conducted in order to elucidate the mode of action of the HtpR protein. Using luxR-lacZ fused genes, we showed that the HtpR protein is essential for the maximum expression of beta-galactosidase activity in Escherichia coli lac mutant cells. Using this construct, we also demonstrated that luxR is preferentially expressed toward the end of the logarithmic phase of growth. Starvation and addition of ethanol significantly advanced the appearance of beta-galactosidase activity in htpR+ cells. The luminescence system of E. coli htpR+ cells harboring the pChv1 plasmid with a deletion in the luxI gene is induced in the presence of low and constant concentrations (150 pg/ml) of the inducer only at a late stage of the logarithmic phase of growth. When the cellular LuxR content is reduced, following 23 generations of exponential growth in Luria broth, a mid-log-phase culture does not respond to the inducer (150 pg/ml). On the basis of the above observations we suggest that the HtpR protein controls the formation of V. fischeri LuxR protein. Preliminary findings indicate that the HtpR protein acts through the chaperonins GroESL. E. coli htpR/pChv1 cells retained their full level of in vivo and in vitro luciferase activities in the presence of multiple copies of groESL genes. The possibility that GroESL proteins stabilize the native form of LuxR protein is discussed. PMID- 1429437 TI - Activity of mutant sigma F proteins truncated near the C terminus. AB - sigma F, the product of the spoIIAC gene of Bacillus subtilis, is homologous in amino acid sequence throughout most of its length with several other sigma factors of B. subtilis and Escherichia coli. However, 8 residues from the C terminus the homology abruptly breaks down, suggesting that the C-terminal tail of the protein may be dispensable. It is known that an amber mutation at the 11th codon (wild-type glutamine 245) from the C terminus abolishes the function of the sigma factor. We have now placed chain-terminating codons at the ninth codon (wild-type lysine 247), the eighth codon (wild-type valine 248), or the seventh codon (wild-type glutamine 249) from the C terminus. We have tested the resulting mutants for their capacity to sporulate and for their ability to transcribe from a promoter (spoIIIG) that is normally read by RNA polymerase bound to sigma F (E sigma F). The results indicate that a mutant sigma F lacking the terminal 7 residues functions almost normally, which suggests that glutamine 249 is dispensable. By contrast, lysine 247 is crucial for the activity of sigma F: deletion of the 9 C-terminal residues totally inactivates the protein. When the terminal 8 residues were deleted, placing lysine 247 at the C terminus, the transcriptional activity of the factor is reduced by about 80%: we attribute this effect to neutralization of the positive charge of lysine 247 by formation of a salt bridge with the -COO- terminus. PMID- 1429438 TI - Ultrastructural examination of the lipopolysaccharides of Pseudomonas aeruginosa strains and their isogenic rough mutants by freeze-substitution. AB - The majority of Pseudomonas aeruginosa strains synthesize two antigenically distinct types of lipopolysaccharide (LPS), namely, a serotype-specific B-band LPS and a common antigen A-band LPS. A-band LPS consists of uncharged poly-D rhamnan, which does not bind uranyl ions and is difficult to stain for electron microscopy; the highly charged B-band LPS is more easily visualized. We selected two wild-type strains, PAO1 (serotype O5) and IATS O6 (serotype O6), generated isogenic mutants from them, and examined the distribution of LPS on the surface of these organisms by freeze-substitution and electron microscopy. On PAO1 cells, which express both A-band and B-band LPSs, a 31- to 36-nm-wide fringe extending perpendicularly from the outer membrane was observed. A fine fibrous material was also observed on the surface of serotype O6 (A+ B+) cells, although this material did not form a uniform layer. When the LPS-deficient mutants, strains AK1401 (A+ B-), AK 1012 (A- B-), rd7513 (A- B-), and R5 (an IATS O6-derived rough mutant; A- B-), were examined, no extraneous material was apparent above the bilayer. However, an asymmetrical staining pattern was observed on the outer leaflet of the outer membrane of each of these mutants, presumably conforming to the anionic charge distribution of the core region of the rough LPS. In all cases, expression of the LPS types was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining. When optical densitometry on electron microscopy negatives was used to analyze the outer membrane staining profiles, subtle differences in the degrees of core deficiency among rough mutants were detectable. This is the first time an electron microscopy technique has preserved the infrastructure produced in the outer membrane by its constituent macromolecules. We conclude that freeze-substitution electron microscopy is effective in the visualization of LPS morphotypes. PMID- 1429439 TI - Fatty acids are precursors of alkylamines in Deinococcus radiodurans. AB - Deinococcus radiodurans contains novel phospholipids of which the structures of three have been previously described. These three lipids contain both fatty acids and alkylamines. Both the fatty acid and alkylamine constituents were found to be composed of a mixture of species, of which C15, C16, and C17 saturated and monounsaturated alkyl chains predominated. Alkylamines contained a relatively higher proportion of saturated species. Progression of bacterial growth through the mid-log to stationary phases was accompanied by an increase in the proportions of C15 and C17 alkyl chains in both fatty acid and alkylamine constituents. Radiolabeled palmitic acid was found to be rapidly incorporated into both fatty acid and alkylamine components of phosphatidylglyceroylalkylamine, which is the precursor of the more-complex phosphoglycolipids found in major amounts in D. radiodurans. After culturing D. radiodurans in the presence of a mixture of palmitic acids labeled with 14C and 3H in the 1 and 9,10 positions, respectively, the same 14C/3H ratio was recovered in both fatty acid and alkylamine constituents, strongly suggesting that alkylamines are derived from intact fatty acids rather than by a de novo pathway. The results identify a novel product of fatty acid metabolism which has not to date been observed in any other organism. PMID- 1429440 TI - An internal region of rpoB is required for autogenous translational regulation of the beta subunit of Escherichia coli RNA polymerase. AB - In order to delineate the region involved in feedback regulation of the RNA polymerase beta subunit (encoded by rpoB), a collection of rpoB-lacZ translational fusions with different endpoints both upstream and downstream of the rpoB start site was assembled on lambda phage vectors. The extent of translational repression of beta was monitored by measuring beta-galactosidase levels in monolysogens of the fusions under conditions of increased intracellular concentrations of beta and beta' achieved via the induction of rpoBC expression from a multicopy plasmid. A construct containing as little as 29 bp upstream of the start of rpoB exhibited repression of beta-galactosidase activity to the same extent as a construct encoding the full upstream region. A construct which carried only 70 bp of the rpoB structural gene exhibited very little repression, while constructs which carried 126 or 221 bp of rpoB exhibited approximately the same degree of repression as a construct which carried 403 bp. These data suggest that the sequences important for feedback regulation of beta translation extend more than 70 bp into rpoB but are completely contained within a region which spans the sequences from 29 bp upstream to 126 bp downstream of the translational start site. PMID- 1429441 TI - Phenotypes of sphingolipid-dependent strains of Saccharomyces cerevisiae. AB - To study sphingolipid function(s) in Saccharomyces cerevisiae, we have investigated the effects of environmental stress on mutant (SLC) strains (R. C. Dickson, G. B. Wells, A. Schmidt, and R. L. Lester, Mol. Cell. Biol. 10:2176 2181, 1990) that either contain or lack sphingolipids, depending on whether they are cultured with a sphingolipid long-chain base. Strains lacking sphingolipid were unable to grow at low pH, at 37 degrees C, or with high salt concentrations in the medium; these environmental stresses are known to inhibit the growth of some S. cerevisiae strains with a defective plasma membrane H(+)-ATPase. We found that sphingolipids were essential for proton extrusion at low pH and furthermore found that cells lacking sphingolipid no longer exhibited net proton extrusion at normal pH after a 1-min exposure to pH 3. Cells lacking sphingolipid appeared to rapidly become almost completely permeable to protons at low pH. The deleterious effects of low pH could be partially prevented by 1 M sorbitol in the suspension of cells lacking sphingolipid. Proton extrusion at normal pH (pH 6) was significantly inhibited at 39 degrees C only in cells lacking sphingolipid. Thus, the product of an SLC suppressor gene permits life without sphingolipids only in a limited range of environments. Outside this range, sphingolipids appear to be essential for maintaining proton permeability barriers and/or for proton extrusion. PMID- 1429442 TI - A locus that contributes to colonization of the intestinal tract by Bacteroides thetaiotaomicron contains a single regulatory gene (chuR) that links two polysaccharide utilization pathways. AB - Previously, we isolated two Tn4351-generated mutants of Bacteroides thetaiotaomicron (46-1 and CS3) that were unable to grow either on heparin or on chondroitin sulfate. This phenotype was unexpected, since the heparin and chondroitin sulfate utilization pathways had appeared from earlier studies to be independent of each other. Mutants 46-1 and CS3 were also of interest because both were unable to compete successfully with wild-type B. thetaiotaomicron in the intestinal tracts of germfree mice. Thus, both appeared to have a colonization defect. We have now cloned the chromosomal locus in which the transposon insertions in 46-1 and CS3 occurred. Southern blot analysis showed that the Tn4351 insertions in 46-1 and CS3 were about 100 bp apart. Using complementation and insertional mutagenesis, we localized the region affected by the 46-1 and CS3 insertions to within 2.5 kbp. This DNA segment was sequenced and found to contain a 401-codon open reading frame (ORF1) and the N-terminal segment of a second open reading frame (ORF2), which was downstream of ORF1 and transcribed in the same direction. The deduced amino acid sequence of ORF1 showed significant homology to that of a putative positive regulator of an arylsulfatase gene in Klebsiella aerogenes. ORF2 was at least 381 amino acids long and did not exhibit homology to any proteins in the data bases searched. Transposon insertions in both mutants 46-1 and CS3 disrupted ORF1. The results of insertional mutagenesis and complementation experiments indicated that ORF2 was not essential for growth on chondroitin sulfate or heparin. Thus, the chondroitin sulfate-negative and heparin-negative phenotypes of 46-1 and CS3 appear to be due to the interruption of a regulatory gene encoded by ORF1 and not to a polar effect of the insertions on a downstream gene(s). The gene encoding ORF1 has been designated chuR, for regulation of chondroitin sulfate and heparin utilization. Transcriptional fusion studies showed that the expression of chuR occurred at the same level under inducing and noninducing conditions, in contrast to the regulated expression of structural genes of the chondroitin sulfate utilization system. chuR was not autoregulated, nor was its expression affected by a mutation (46-4) that eliminated the expression of all chondroitin sulfate utilization genes but did not affect the utilization of heparin. PMID- 1429443 TI - Regulation of the BamHI restriction-modification system by a small intergenic open reading frame, bamHIC, in both Escherichia coli and Bacillus subtilis. AB - BamHI, from Bacillus amyloliquefaciens H, is a type II restriction-modification system recognizing and cleaving the sequence G--GATCC. The BamHI restriction modification system contains divergently transcribed endonuclease and methylase genes along with a small open reading frame oriented in the direction of the endonuclease gene. The small open reading frame has been designated bamHIC (for BamHI controlling element). It acts as both a positive activator of endonuclease expression and a negative repressor of methylase expression of BamHI clones in Escherichia coli. Methylase activity increased 15-fold and endonuclease activity decreased 100-fold when bamHIC was inactivated. The normal levels of activity for both methylase and endonuclease were restored by supplying bamHIC in trans. The BamHI restriction-modification system was transferred into Bacillus subtilis, where bamHIC also regulated endonuclease expression when present on multicopy plasmid vectors or integrated into the chromosome. In B. subtilis, disruption of bamHIC caused at least a 1,000-fold decrease in endonuclease activity; activity was partially restored by supplying bamHIC in trans. PMID- 1429444 TI - Characterization of the Escherichia coli membrane domain responsible for binding oriC DNA. AB - It has previously been shown that hemimethylated DNA from the Escherichia coli replication origin (oriC) binds with high specificity to membrane fractions isolated from disrupted cells. In this article, the membrane localization of oriC binding activity was studied by subjecting crude membrane preparations to successive cycles of sedimentation and flotation gradient analysis. This revealed that approximately two-thirds of the membrane-associated oriC-binding activity of the cell was not associated with the outer membrane fraction as previously suggested but was recovered instead in a unique membrane fraction (OCB1) whose buoyant density and protein profile differed from those of both inner and outer membranes. The specific activity of oriC binding in OCB1 was approximately fivefold higher than the activity of the isolated outer membrane peak. It is likely that membrane fraction OCB1 includes the membrane domain responsible for the binding of hemimethylated oriC to the cell envelope in intact cells. PMID- 1429445 TI - Chromosomal structure of the halophilic archaebacterium Halobacterium salinarium. AB - The chromosomal structure of the extremely halophilic archaebacterium Halobacterium salinarium was examined. Sheared chromosomes prepared from the bacteria in the late exponential phase were separated into two peaks (peaks I and II) by sucrose gradient centrifugation, suggesting that the chromosomes consist of two parts differing in quality. The UV spectra of peaks I and II resembled those of DNA and eukaryotic chromatin, respectively. Electron microscopic observations revealed that the major component of peak I was protein-free DNA, while the major components of peak II were rugged thick fibers with a diameter of 17 to 20 nm. The rugged fibers basically consisted of bacterial nucleosome-like structures composed of DNA and protein, as demonstrated in experiments with proteinase and nuclease digestion. Whole-mount electron microscopic observations of the chromosomes directly spread onto a water surface revealed a configuration in which the above-described regions were localized on a continuous DNA fiber. From these results it is concluded that the H. salinarium chromosome is composed of regions of protein-free DNA and DNA associated with nucleosome-like structures. Peaks I and II were predominant in the early exponential phase and stationary phase, respectively; therefore, the transition of the chromosome structure between non-protein-associated and protein-associated forms seems to be related to the bacterial growth phase. PMID- 1429446 TI - Multiple forms of bile salt hydrolase from Lactobacillus sp. strain 100-100. AB - Four isozymes of bile salt hydrolase (BSH) have been purified from the cytosol of cells of Lactobacillus sp. strain 100-100. The four proteins were designated BSH A, B, C, and D. They eluted from anion-exchange high-pressure liquid chromatography columns at 0.15, 0.18, 0.21, and 0.25 M NaCl, respectively. They are catalytically similar, except that the Vmax of BSH D is about 10-fold lower than those of the other three isozymes. All four proteins consist of one or two polypeptides. The peptides have molecular weights of 42,000 and 38,000 and are designated alpha and beta, respectively. The approximate native molecular weights of BSH A, B, C, and D are 115,000, 105,000, 95,000, and 80,000, respectively. The native proteins are probably trimers; the four isozymes are the array of possible subunit combinations alpha 3, alpha 2 beta 1, alpha 1 beta 2, and beta 3 for A, B, C, and D, respectively. The two subunits are antigenically distinct. Polyclonal antibodies raised against BSH A (all alpha peptide) react in Western blots (immunoblots) only with proteins containing the alpha peptide; such antibodies raised against BSH D (all beta peptide) react only with proteins containing the beta peptide. The amino acid compositions of the two peptides differ. This is the first report of a bacterium that makes four BSH isozymes. PMID- 1429447 TI - The helix-turn-helix motif of sigma 54 is involved in recognition of the -13 promoter region. AB - Residue Arg-383 in the proposed helix-turn-helix motif of the novel RNA polymerase sigma factor sigma 54 has been changed by site-directed mutagenesis to all possible alternative amino acids. Only two mutants, RK383 and RH383, are active in promoting transcription from either the glnAp2 promoter or the nifL promoter. We constructed a set of mutant derivatives of glnAp2 such that each base in the conserved GG and GC doublets at -24 and -12 was changed to all possible alternatives. All 12 mutant glnAp2 promoters showed a marked promoter down phenotype with wild-type sigma 54, but RK383 suppressed changes of both G to C and G to T at -13. This result suggests that the sigma 54 helix-turn-helix is involved in recognition of the -13 region of sigma 54-dependent promoters. PMID- 1429448 TI - Physical map of the Methanobacterium thermoautotrophicum Marburg chromosome. AB - A physical map of the Methanobacterium thermoautotrophicum Marburg chromosome was constructed by using pulsed-field gel electrophoresis of restriction fragments generated by NotI, PmeI, and NheI. The order of the fragments was deduced from Southern blot hybridization of NotI fragment probes to various restriction digests and from partial digests. The derived map is circular, and the genome size was estimated to be 1,623 kb. Several cloned genes were hybridized to restriction fragments to locate their positions on the map. Genes coding for proteins involved in the methanogenic pathway were located on the same segment of the circular chromosome. In addition, the genomes of a variety of thermophilic Methanobacterium strains were treated with restriction enzymes and analyzed by pulsed-field gel electrophoresis. The sums of the fragment sizes varied from 1,600 to 1,728 kb among the strains, and widely different macrorestriction patterns were observed. PMID- 1429449 TI - Cloning of a metalloprotease gene involved in the virulence mechanism of Vibrio anguillarum. AB - Genetic evidence has previously suggested that a zinc metalloprotease is involved in the invasive mechanism of the fish pathogen Vibrio anguillarum NB10. In this study, the metalloprotease gene was cloned and sequenced. The sequence encodes a polypeptide (611 amino acids) that contains a putative signal sequence followed by a large leader sequence and the mature protein (44.6 kDa). Since the purified protein has a molecular mass of 36 kDa instead of the predicted 44.6 kDa, the mature protein is most likely processed a third time. Comparative analyses of the protein sequence showed high homologies to other bacterial metalloproteases within the zinc-binding and active-site regions. The Vibrio cholerae hemagglutinin/protease and the Pseudomonas aeruginosa elastase were exceptions in that the homology extended throughout the entire putative preproprotein. A chromosomal metalloprotease mutant was made via the integration of foreign DNA into the protease gene. This mutant did not secrete the metalloprotease, as determined by sodium dodecyl sulfate (SDS)-polyacrylamide protein analysis and by growth on gelatin agar. Transcomplementation of the chromosomal mutation revived the secretion of the metalloprotease and its activity on gelatin agar. Interestingly, when supernatant proteins were analyzed by gelatin-SDS polyacrylamide electrophoresis, two different proteases (75 and 30 kDa) were detected in the mutant strain but not in the transcomplemented strain or the wild type strain. Moreover, fish infection studies were done, and implications for the role of the metalloprotease in the virulence mechanism of V. anguillarum are discussed. PMID- 1429450 TI - Use of chromosomal gene fusions to investigate the role of repetitive DNA in regulation of genes involved in lipopolysaccharide biosynthesis in Haemophilus influenzae. AB - The lic3 locus of Haemophilus influenzae consists of four open reading frames. The derived amino acid sequences of orf2 and orf4 exhibit homology to Escherichia coli GalE and AdK, respectively. The functions of orf1 and orf3 remain unknown. orf1 contains multiple tandem repeats of the tetrameric DNA sequence CAAT near the 5' end. Two possible translational starts (ATG1 and ATG2) lie upstream. We have used lacZ fusions to investigate whether changes in the number of CAAT repeats in conjunction with differential usage of the upstream frames control the expression of lic3-orf1. Phase-variable expression of lacZ was observed for individual colonies and could be related to variable numbers of CAAT repeats. Of the three possible upstream frames, only one, containing the more downstream of the two possible ATG start codons (ATG2), is used for strong expression of lacZ. Utilization of the more upstream ATG (ATG1) or ATG2 was observed with medium level expression, while utilization of any of the three possible frames was observed when lacZ was expressed at low to undetectable levels, indicating that other mechanisms may affect expression. To investigate this, lacZ was fused in frame with ATG2 of lic3-orf1, with concomitant deletion of the repeats. Phase variable expression was still observed, supporting the view that an alternative level of control operates in conjunction with the repeat mechanism. PMID- 1429451 TI - Identification of a new gene, tmoF, in the Pseudomonas mendocina KR1 gene cluster encoding toluene-4-monooxygenase. AB - Five genes, tmoABCDE, encoding toluene-4-monooxygenase (T4MO) were previously mapped to a 3.6-kb region of a 10.2-kb SacI DNA fragment isolated from Pseudomonas mendocina KR1 (K.-M. Yen, M. R. Karl, L. M. Blatt, M. J. Simon, R. B. Winter, P. R. Fausset, H. S. Lu, A. A. Harcourt, and K. K. Chen, J. Bacteriol. 173:5315-5327, 1991). In this report, we describe the identification and characterization of a DNA region in the SacI fragment whose expression enhances the T4MO activity determined by the tmoABCDE gene cluster. This region was mapped immediately downstream of the putative transcription termination sequence previously located at the end of the tmoABCDE gene cluster (Yen et al., J. Bacteriol., 1991) and was found to stimulate T4MO activity two- to threefold when expressed in Escherichia coli or Pseudomonas putida. Determination of the nucleotide sequence of this region revealed an open reading frame (ORF) of 978 bp. Expression of the ORF resulted in the synthesis of an approximately 37-kDa polypeptide whose N-terminal amino acid sequence completely matched that of the product predicted from the ORF. The ORF thus defines a gene, which has now been designated tmoF. The TmoF protein shares amino acid sequence homology with the reductases of several mono- and dioxygenase systems. In addition, the reductase component of the naphthalene dioxygenase system, encoded by the nahAa gene of plasmid NAH7 from P. putida G7, could largely replace the TmoF protein in stimulating T4MO activity, and TmoF could partially replace the NahAa protein in forming active naphthalene dioxygenase. The overall properties of tmoF suggest that it is a member of the T4mo gene cluster and encodes the NADH:ferredoxin oxidoreductase of the T4MO system. PMID- 1429452 TI - Regulation of partitioned sterol biosynthesis in Saccharomyces cerevisiae. AB - Using yeast strains with null mutations in structural genes which encode delta aminolevulinic acid synthetase (HEM1), isozymes of 3-hydroxy-3-methylglutaryl coenzyme A (HMG1 and HMG2), squalene epoxidase (ERG1), and fatty acid delta 9 desaturase (OLE1), we were able to determine the effect of hemes, sterols, and unsaturated fatty acids on both sterol production and the specific activity of 3 hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in Saccharomyces cerevisiae. We found that the HMGR isozymes direct essentially equal amounts of carbon to the biosynthesis of sterols under heme-competent conditions, despite a huge disparity (57-fold) in the specific activities of the reductases. Our results demonstrate that palmitoleic acid (16:1) acts as a rate-limiting positive regulator and that ergosterol acts as a potent inhibitor of sterol production in strains which possess only the HMGR1 isozyme (HMG1 hmg2). In strains which contain only the HMGR2 isozyme (hmg1 HMG2), sterol production was inhibited by oleic acid (18:1) and to a lesser degree by ergosterol. The specific activities of the two reductases (HMGR1 and HMGR2) were found to be differentially regulated by hemes but not by ergosterol, palmitoleic acid, or oleic acid. The disparate effects of unsaturated fatty acids and sterols on these strains lead us to consider the possibility of separate, compartmentalized isoprenoid pathways in S. cerevisiae. PMID- 1429454 TI - The terminal reductases for selenate and nitrate respiration in Thauera selenatis are two distinct enzymes. AB - A number of approaches have been used to show that a recently isolated selenate respiring bacterium, Thauera selenatis, is able to synthesize both a selenate reductase (SR) and a nitrate reductase (NR). (i) The pH optimum of the SR was found to be 6.0; that of the NR was 7.0. (ii) The presence of nitrate did not inhibit selenate reduction in selenate-grown cells. (iii) In cell extracts, the highest SR or NR activity was observed in cells grown with the respective electron acceptor. (iv) Mutants that were unable to grow with nitrate as the terminal electron acceptor and lacked NR activity were isolated; these mutants grew normally with selenate and synthesized SR. (v) The SR was found in the periplasmic space of the cell, whereas the NR was present in the cytoplasmic membrane. A hypothetical electron transport system involving the SR is described. PMID- 1429453 TI - Construction of an EcoRI restriction map of Mycoplasma pneumoniae and localization of selected genes. AB - A restriction map of the genome of Mycoplasma pneumoniae, a small human pathogenic bacterium, was constructed by means of an ordered cosmid library which spans the complete bacterial chromosome. The positions of 143 endonuclease EcoRI restriction fragments were determined and aligned with the physical map. In addition, restriction sites for the rare-cutting enzymes XhoI (25 sites), ApaI (13 sites), NotI (2 sites), and SfiI (2 sites) were included. The resulting map consists of 185 restriction sites, has a mean resolution of 4.4 kbp, and predicts a genome size of 809 kbp. In addition, several genes were identified and mapped to their respective genomic EcoRI restriction fragments. PMID- 1429455 TI - The gene encoding a Prevotella loescheii lectin-like adhesin contains an interrupted sequence which causes a frameshift. AB - We cloned and sequenced the Prevotella loescheii gene plaA, which encodes a lectin-like adhesin that mediates the coaggregation of P. loescheii 1295 with Streptococcus oralis 34. A probe derived from the N-terminal amino acid sequence of the purified adhesin was used to identify the plaA gene from a P. loescheii genomic library constructed in lambda GEM-11. Sequence analysis of plaA indicates that the initial translation product contains a 22-amino-acid leader. The reading frame of the plaA gene is interrupted after amino acid 28 of the mature protein by a TAA termination codon. Amplification of the P. loescheii genomic DNA in the region surrounding this codon by the polymerase chain reaction followed by DNA sequencing of the cloned DNA fragment established that this stop codon was not an experimental artifact. A frameshift beginning 29 bp downstream of the ochre terminator was required to access the only large open reading frame in the gene. Amino acid sequences of six purified peptides derived by limited proteolysis of adhesin with endoproteinase Lys-C matched the downstream amino acid sequence derived by translation of the large open reading frame. The gene coding sequence of 2.4 kb contains sufficient information for the synthesis of an 89-kDa protein. A putative rho-independent terminator (delta G = -25.5 kcal/mol [ca. -107 kJ/mol]) was detected 38 bp downstream from the plaA stop codon. PMID- 1429456 TI - The Calvin cycle enzyme pentose-5-phosphate 3-epimerase is encoded within the cfx operons of the chemoautotroph Alcaligenes eutrophus. AB - Several genes (cfx genes) encoding Calvin cycle enzymes in Alcaligenes eutrophus are organized in two highly homologous operons comprising at least 11 kb. One cfx operon is located on the chromosome; the other is located on megaplasmid pHG1 of the organism (B. Bowien, U. Windhovel, J.-G. Yoo, R. Bednarski, and B. Kusian, FEMS Microbiol. Rev. 87:445-450, 1990). Corresponding regions of about 2.7 kb from within the operons were sequenced. Three open reading frames, designated cfxX (954 bp), cfxY (765 bp), and cfxE (726 bp), were detected at equivalent positions in the two sequences. The nucleotide identity of the sequences amounted to 94%. Heterologous expression of the subcloned pHG1-encoded open reading frames in Escherichia coli suggested that they were functional genes. The observed sizes of the gene products CfxX (35 kDa), CfxY (27 kDa), and CfxE (25.5 kDa) closely corresponded to the values calculated on the basis of the sequence information. E. coli clones harboring the cfxE gene showed up to about 19-fold-higher activities of pentose-5-phosphate 3-epimerase (PPE; EC 5.1.3.1) than did reference clones, suggesting that cfxE encodes PPE, another Calvin cycle enzyme. These data agree with the finding that in A. eutrophus, PPE activity is significantly enhanced under autotrophic growth conditions which lead to a derepression of the cfx operons. No functions could be assigned to CfxX and CfxY. PMID- 1429458 TI - A-signalling and the cell density requirement for Myxococcus xanthus development. AB - Mutations in any of three asg (A-signalling) loci cause fruiting body development of Myxococcus xanthus to arrest at about the 2-h stage. Development can be restored to asg mutants by the addition of conditioned buffer in which wild-type cells have been developing or of A-factor purified from the conditioned buffer. Two forms of A-factor have been identified: heat-stable A-factor, which is composed of amino acids and peptides, and heat-labile A-factor, which consists of at least two proteases. A-factor is found in conditioned buffer in rough proportion to the cell density. As decreasing amounts of either form of A-factor are added, the developmental response of asg cells decreases until a threshold concentration is reached, below which no response is detected. In addition, wild type cells fail to develop when their density is decreased below the point at which the level of A-factor is predicted to fall short of this threshold. The development of low-density asg+ cells can, however, be restored by the addition of either form of A-factor. These experiments show that A-factor is important for the development of wild-type cells. Moreover, the development of an asgB mutant that produces 5 to 10% the wild-type level of A-factor can be restored when the cell density is increased 10-fold above the standard density. We propose that the A-signal is used by M. xanthus to specify the minimum cell density required for the initiation of development. Differences in the response to A-factor between different asg mutants suggest that the different asg loci govern A-factor production in diverse ways. PMID- 1429457 TI - Kinetics and sequence specificity of processing of prepilin by PilD, the type IV leader peptidase of Pseudomonas aeruginosa. AB - PilD, originally isolated as an essential component for the biogenesis of the type IV pili of Pseudomonas aeruginosa, is a unique endopeptidase responsible for processing the precursors of the P. aeruginosa pilin subunits. It is also required for the cleavage of the leader peptides from the Pdd proteins, which are essential components of an extracellular secretion pathway specific for the export of a number of P. aeruginosa hydrolytic enzymes and toxins. Substrates for PilD are initially synthesized with short, i.e., 6- to 8-amino-acid-long, leader peptides with a net basic charge and share a high degree of amino acid homology through the first 16 to 30 residues at the amino terminus. In addition, they all have a phenylalanine residue at the +1 site relative to the cleavage site, which is N methylated prior to assembly into the oligomeric structures. In this study, the kinetics of leader peptide cleavage from the precursor of the P. aeruginosa pilin subunit by PilD was determined in vitro. The rates of cleavage were compared for purified enzyme and substrate as well as for enzyme and substrate contained within total membranes extracted from P. aeruginosa strains overexpressing the cloned pilD or pilA genes. Optimal conditions were obtained only when both PilD and substrate were contained within total membranes. PilD catalysis of P. aeruginosa prepilin followed normal Michaelis-Menten kinetics, with a measured apparent Km of approximately 650 microM, and a kcat of 180 min-1. The kinetics of PilD processing of another type IV pilin precursor, that from Neisseria gonorrhoeae with a 7-amino-acid-long leader peptide, were essentially the same as that measured for wild-type P. aeruginosa prepilin. Quite different results were obtained for a number of prepilin substrates containing substitutions at the conserved phenylalanine at the +1 position relative to the cleavage site, which were previously shown to be well tolerated in vivo. Substitutions of methionine, serine, and cysteine for phenylalanine show that Km values remain close to that measured for wild-type substrate, while kcat and kcat/Km values were significantly decreased. This indicates that while the affinity of enzyme for substrate is relatively unaffected by the substitutions, the maximum rate of catalysis favors a phenylalanine at this position. Interesting, PilD cleavage of one mutated pillin (asparagine) resulted in a lower Km value of 52.5 microM, which indicates a higher affinity for the enzyme, as well as a lower kcat value of 6.1 min m(-1). This suggests that it may be feasible to design peptide inhibitors of PilD. PMID- 1429459 TI - Use of the tac promoter and lacIq for the controlled expression of Zymomonas mobilis fermentative genes in Escherichia coli and Zymomonas mobilis. AB - The Zymomonas mobilis genes encoding alcohol dehydrogenase I (adhA), alcohol dehydrogenase II (adhB), and pyruvate decarboxylase (pdc) were overexpressed in Escherichia coli and Z. mobilis by using a broad-host-range vector containing the tac promoter and the lacIq repressor gene. Maximal IPTG (isopropyl-beta-D thiogalactopyranoside) induction of these plasmid-borne genes in Z. mobilis resulted in a 35-fold increase in alcohol dehydrogenase I activity, a 16.7-fold increase in alcohol dehydrogenase II activity, and a 6.3-fold increase in pyruvate decarboxylase activity. Small changes in the activities of these enzymes did not affect glycolytic flux in cells which are at maximal metabolic activity, indicating that flux under these conditions is controlled at some other point in metabolism. Expression of adhA, adhB, or pdc at high specific activities (above 8 IU/mg of cell protein) resulted in a decrease in glycolytic flux (negative flux control coefficients), which was most pronounced for pyruvate decarboxylase. Growth rate and flux are imperfectly coupled in this organism. Neither a twofold increase in flux nor a 50% decline from maximal flux caused any immediate change in growth rate. Thus, the rates of biosynthesis and growth in this organism are not limited by energy generation in rich medium. PMID- 1429460 TI - Lysine biosynthesis in selected pathogenic fungi: characterization of lysine auxotrophs and the cloned LYS1 gene of Candida albicans. AB - The alpha-aminoadipate pathway for the biosynthesis of lysine is present only in fungi and euglena. Until now, this unique metabolic pathway has never been investigated in the opportunistic fungal pathogens Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. Five of the eight enzymes (homocitrate synthase, homoisocitrate dehydrogenase, alpha-aminoadipate reductase, saccharopine reductase, and saccharopine dehydrogenase) of the alpha-aminoadipate pathway and glucose-6-phosphate dehydrogenase, a glycolytic enzyme used as a control, were demonstrated in wild-type cells of these organisms. All enzymes were present in Saccharomyces cerevisiae and the pathogenic organisms except C. neoformans 32608 serotype C, which exhibited no saccharopine reductase activity. The levels of enzyme activity varied considerably from strain to strain. Variation among organisms was also observed for the control enzyme. Among the pathogens, C. albicans exhibited much higher homocitrate synthase, homoisocitrate dehydrogenase, and alpha-aminoadipate reductase activities. Seven lysine auxotrophs of C. albicans and one of Candida tropicalis were characterized biochemically to determine the biochemical blocks and gene-enzyme relationships. Growth responses to alpha-aminoadipate- and lysine-supplemented media, accumulation of alpha-aminoadipate semialdehyde, and the lack of enzyme activity revealed that five of the mutants (WA104, WA153, WC7-1-3, WD1-31-2, and A5155) were blocked at the alpha-aminoadipate reductase step, two (STN57 and WD1-3-6) were blocked at the saccharopine dehydrogenase step, and the C. tropicalis mutant (X-16) was blocked at the saccharopine reductase step. The cloned LYS1 gene of C. albicans in the recombinant plasmid YpB1078 complemented saccharopine dehydrogenase (lys1) mutants of S. cerevisiae and C. albicans. The Lys1+ transformed strains exhibited significant saccharopine dehydrogenase activity in comparison with untransformed mutants. The cloned LYS1 gene has been localized on a 1.8-kb HindIII DNA insert of the recombinant plasmid YpB1041RG1. These results established the gene-enzyme relationship in the second half of the alpha aminoadipate pathway. The presence of this unique pathway in the pathogenic fungi could be useful for their rapid detection and control. PMID- 1429461 TI - Analysis of eight out genes in a cluster required for pectic enzyme secretion by Erwinia chrysanthemi: sequence comparison with secretion genes from other gram negative bacteria. AB - Many extracellular proteins produced by Erwinia chrysanthemi require the out gene products for transport across the outer membrane. In a previous report (S. Y. He, M. Lindeberg, A. K. Chatterjee, and A. Collmer, Proc. Natl. Acad. Sci. USA 88:1079-1083, 1991) cosmid pCPP2006, sufficient for secretion of Erwinia chrysanthemi extracellular proteins by Escherichia coli, was partially sequenced, revealing four out genes sharing high homology with pulH through pulK from Klebsiella oxytoca. The nucleotide sequence of eight additional out genes reveals homology with pulC through pulG, pulL, pulM, pulO, and other genes involved in secretion by various gram-negative bacteria. Although signal sequences and hydrophobic regions are generally conserved between Pul and Out proteins, four out genes contain unique inserts, a pulN homolog is not present, and outO appears to be transcribed separately from outC through outM. The sequenced region was subcloned, and an additional 7.6-kb region upstream was identified as being required for secretion in E. coli. out gene homologs were found on Erwinia carotovora cosmid clone pAKC651 but were not detected in E. coli. The outC through-outM operon is weakly induced by polygalacturonic acid and strongly expressed in the early stationary phase. The out and pul genes are highly similar in sequence, hydropathic properties, and overall arrangement but differ in both transcriptional organization and the nature of their induction. PMID- 1429462 TI - Purification of two chitinases from Rhizopus oligosporus and isolation and sequencing of the encoding genes. AB - Two chitinases were purified from Rhizopus oligosporus, a filamentous fungus belonging to the class Zygomycetes, and designated chitinase I and chitinase II. Their N-terminal amino acid sequences were determined, and two synthetic oligonucleotide probes corresponding to these amino acid sequences were synthesized. Southern blot analyses of the total genomic DNA from R. oligosporus with these oligonucleotides as probes indicated that one of the two genes encoding these two chitinases was contained in a 2.9-kb EcoRI fragment and in a 3.6-kb HindIII fragment and that the other one was contained in a 2.9-kb EcoRI fragment and in a 11.5-kb HindIII fragment. Two DNA fragments were isolated from the phage bank of R. oligosporus genomic DNA with the synthetic oligonucleotides as probes. The restriction enzyme analyses of these fragments coincided with the Southern blot analyses described above and the amino acid sequences deduced from their nucleotide sequences contained those identical to the determined N-terminal amino acid sequences of the purified chitinases, indicating that each of these fragments contained a gene encoding chitinase (designated chi 1 and chi 2, encoding chitinase I and II, respectively). The deduced amino acid sequences of these two genes had domain structures similar to that of the published sequence of chitinase of Saccharomyces cerevisiae, except that they had an additional C terminal domain. Furthermore, there were significant differences between the molecular weights experimentally determined with the two purified enzymes and those deduced from the nucleotide sequences for both genes. Analysis of the N- and C-terminal amino acid sequences of both chitinases and comparison of them with the amino acid sequences deduced from the nucleotide sequences revealed posttranslational processing not only at the N-terminal signal sequences but also at the C-terminal domains. It is concluded that these chitinases are synthesized with pre- and prosequences in addition to the mature enzyme sequences and that the prosequences are located at the C terminal. PMID- 1429463 TI - S-layer protein gene of Lactobacillus brevis: cloning by polymerase chain reaction and determination of the nucleotide sequence. AB - The surface (S)-layer protein of Lactobacillus brevis was isolated, purified, and characterized. The S-layer protein is the major protein of the cell, with an apparent molecular mass of 46 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Immunogold electron microscopy with polyclonal antiserum against the isolated 46-kDa protein was used to confirm the surface location of this protein. N-terminal amino acid sequences of the intact 46-kDa protein and its tryptic peptides were determined. The gene of the S-layer protein was amplified from the genome of L. brevis by polymerase chain reaction with oligonucleotides, synthesized according to the N-terminal amino acid sequences, as primers. The polymerase chain reaction fragments containing the entire S-layer gene and its regulatory regions were sequenced. Nucleic acid sequence analysis revealed one open reading frame with a capacity to encode a protein of 48,159 Da. From the regulatory region of the gene, two subsequent promoters and a ribosome binding site, showing typical features of prokaryotic consensus sequences, were found. The coding region contained a characteristic gram-positive-type signal peptide of 30 amino acids. Removal of the signal peptide results in a polypeptide of 435 amino acids, which is in excellent agreement with the size of the S-layer protein determined by SDS-PAGE. The size and the 5' end analyses of the S-layer transcripts confirmed the monocistronic nature of the S-layer operon and the functionality of the two promoters found. PMID- 1429464 TI - Microcin 25, a novel antimicrobial peptide produced by Escherichia coli. AB - Microcin 25, a peptide antibiotic excreted by an Escherichia coli strain isolated from human feces, was purified to homogeneity and characterized. Composition analysis and data from gel filtration indicated that microcin 25 may contain 20 amino acid residues. It has a blocked amino-terminal end. Microcin synthesis and immunity are plasmid determined, and the antibiotic was produced in minimal medium when the cultures entered the stationary phase of growth. The peptide appears to interfere with cell division, since susceptible cells filamented when exposed to it. This response does not seem to be mediated by the SOS system. PMID- 1429466 TI - Assay, purification, and characterization of cobaltochelatase, a unique complex enzyme catalyzing cobalt insertion in hydrogenobyrinic acid a,c-diamide during coenzyme B12 biosynthesis in Pseudomonas denitrificans. AB - Hydrogenobyrinic acid a,c-diamide was shown to be the substrate of cobaltochelatase, an enzyme that catalyzes cobalt insertion in the corrin ring during the biosynthesis of coenzyme B12 in Pseudomonas denitrificans. Cobaltochelatase was demonstrated to be a complex enzyme composed of two different components of M(r) 140,000 and 450,000, which were purified to homogeneity. The 140,000-M(r) component was shown to be coded by cobN, whereas the 450,000-M(r) component was composed of two polypeptides specified by cobS and cobT. Each component was inactive by itself, but cobaltochelatase activity was reconstituted upon mixing CobN and CobST. The reaction was ATP dependent, and the Km values for hydrogenobyrinic acid a,c-diamide, Co2+, and ATP were 0.085 +/- 0.015, 4.2 +/- 0.2, and 220 +/- 36 microM, respectively. Spectroscopic data revealed that the reaction product was cob(II)yrinic acid a,c-diamide, and experiments with a coupled-enzyme incubation system containing both cobaltochelatase and cob(II)yrinic acid a,c-diamide reductase (F. Blanche, L. Maton, L. Debussche, and D. Thibaut, J. Bacteriol. 174:7452-7454, 1992) confirmed this result. This report not only provides the first evidence that hydrogenobyrinic acid and its a,c-diamide derivative are indeed precursors of adenosylcobalamin but also demonstrates that precorrin-6x, precorrin-6y, and precorrin-8x, three established precursors of hydrogenobyrinic acid (D. Thibaut, M. Couder, A. Famechon, L. Debussche, B. Cameron, J. Crouzet, and F. Blanche, J. Bacteriol. 174:1043-1049, 1992), are also on the pathway to cobalamin. PMID- 1429465 TI - Physiological consequences of DnaK and DnaJ overproduction in Escherichia coli. AB - The physiological consequences of molecular chaperone overproduction in Escherichia coli are presented. Constitutive overproduction of DnaK from a multicopy plasmid containing large chromosomal fragments spanning the dnaK region resulted in plasmid instability. Co-overproduction of DnaJ with DnaK stabilized plasmid levels. To examine the effects of altered levels of DnaK and DnaJ in a more specific manner, an inducible expression system for dnaK and dnaJ was constructed and characterized. Differential rates of DnaK synthesis were determined by quantitative Western blot (immunoblot) analysis. Moderate levels of DnaK overproduction resulted in a defect in cell septation and formation of cell filaments, but co-overproduction of DnaJ overcame this effect. Further increases in the level of DnaK terminated culture growth despite increased levels of DnaJ. DnaK overproduction was found to be bacteriocidal, and this effect was also partially suppressed by DnaJ. The bacteriocidal effect was apparent only with cultures which were allowed to enter stationary phase, indicating that DnaK toxicity is growth phase dependent. PMID- 1429467 TI - Purification and characterization of Cob(II)yrinic acid a,c-diamide reductase from Pseudomonas denitrificans. AB - An NADH-dependent flavoenzyme exhibiting cob(II)yrinic acid a,c-diamide reductase activity was purified 6,300-fold to homogeneity from Pseudomonas denitrificans and sequenced at its N terminus. This enzyme of the cobalamin biosynthetic pathway reduced to the Co(I) state all of the Co(II)-corrinoids isolated from this microorganism. PMID- 1429468 TI - Sequence of the S-layer gene of Thermus thermophilus HB8 and functionality of its promoter in Escherichia coli. AB - The nucleotide sequence of the slpA gene, which is responsible for the synthesis of the S-layer protein of Thermus thermophilus HB8, is described. This gene is transcribed as a unit in which the coding region is preceded by a 127-base-long leader mRNA sequence. The promoter region is also recognized by the RNA polymerase of Escherichia coli because of the presence of homologous -35 and -10 boxes. Homologies with other promoters from Thermus spp. are also presented. PMID- 1429469 TI - Molecular characterization of a second abortive phage resistance gene present in Lactococcus lactis subsp. lactis ME2. AB - The fifth phage resistance factor from the prototype phage-insensitive strain Lactococcus lactis subsp. lactis ME2 has been characterized and sequenced. The genetic determinant for Prf (phage resistance five) was subcloned from the conjugative plasmid pTN20, which also encodes a restriction and modification system. Typical of other abortive resistance mechanisms, Prf reduces the efficiency of plaquing to 10(-2) to 10(-3) and decreases the plaque size and burst size of the small isometric-headed phage p2 in L. lactis subsp. lactis LM0230. However, normal-size plaques occurred at a frequency of 10(-4) and contained mutant phages that were resistant to Prf, even after repeated propagation through a sensitive host. Prf does not prevent phage adsorption or promote restriction and modification activities, but 90% of Prf+ cells infected with phage p2 die. Thus, phage infections in Prf+ cells are aborted. Prf is effective in both L. lactis subsp. lactis and L. lactis subsp. cremoris strains against several small isometric-headed phages but not against prolate-headed phages. The Prf determinant was localized by Tn5 mutagenesis and subcloning. DNA sequencing identified a 1,056-nucleotide structural gene designated abiC. Prf+ expression was obtained when abiC was subcloned into the lactococcal expression vector pMG36e. abiC is distinct from two other lactococcal abortive phage resistance genes, abiA (Hsp+, from L. lactis subsp. lactis ME2) and abi416 (Abi+, from L. lactis subsp. lactis IL416). Unlike abiA, the action of abiC does not appear to affect DNA replication. Thus, abiC represents a second abortive system found in ME2 that acts at a different point of the phage lytic cycle. PMID- 1429470 TI - Glycine betaine and potassium ion are the major compatible solutes in the extremely halophilic methanogen Methanohalophilus strain Z7302. AB - Methanohalophilus strain Z7302 was previously isolated from a hypersaline environment and grows over a range of NaCl concentrations from 1.7 to 4.4 M. We examined the relationships between cell growth rate, cell volume, and intracellular solute concentrations with increasing salinity. This extremely halophilic methanogen synthesized three zwitterionic compounds, beta-glutamine, N epsilon-acetyl-beta-lysine, and glycine betaine, and also accumulated potassium ion as compatible solutes to balance the external and internal osmotic pressures. Potassium and glycine betaine were the predominant compatible solutes when Methanohalophilus strain Z7302 was grown at high external NaCl concentrations and approached intracellular levels of 3 and 4 M, respectively. PMID- 1429471 TI - Analysis of mutations in cyclodextrin glucanotransferase from Bacillus stearothermophilus which affect cyclization characteristics and thermostability. AB - Cyclodextrin glucanotransferase (CGTase; EC 2.4.1.19) produces cyclodextrin from starch. The CGTase molecule is composed of four globular domains, A, B, C, and D. In order to gain better understanding of the amylolytic and cyclization mechanisms of CGTase, mutant CGTases were constructed from a CGTase gene (cgt1) of Bacillus stearothermophilus NO2. Cgt1-F191Y (Phe at position 191 was replaced by Tyr), Cgt1-F191Y-F255Y, Cgt1-W254V-F255I, Cgt1-W254V, and Cgt1-F255I were constructed for the analysis of the NH2-terminal region. It was revealed that amino acids surrounding a spiral amylose are important for cyclization characteristics and that hydrophobic amino acids just after the Glu catalytic site play an important role in the hydrolysis characteristics of the enzyme. Mutant CGTases Cgt1-T591F and Cgt1-W629F were also constructed to study the role of a second substrate-binding site in domain D, and it was suggested that substrate binding at both domains A and D stabilized the enzyme and optimized cyclodextrin production. PMID- 1429472 TI - A region of the broad-host-range plasmid RK2 causes stable in planta inheritance of plasmids in Rhizobium meliloti cells isolated from alfalfa root nodules. AB - We demonstrate for the first time that the broad-host-range stabilization loci from plasmid RK2 cause total retention of plasmids in cells of Rhizobium meliloti during symbiosis with alfalfa. Two derivatives of plasmid RK2, pRK290 and a 7.3 kb mini-RK2 plasmid, were stabilized in R. meliloti cells isolated from root nodules by the insertion of a 3.2-kb DNA fragment or a smaller 0.8-kb DNA fragment derived from the RK2 stabilization region. PMID- 1429473 TI - A comparative study of nonparaphilic sexual addictions and paraphilias in men. AB - BACKGROUND: A definition of nonparaphilic sexual addiction (NPSA) is offered and the literature suggesting comorbidity between NPSA and paraphilias (PAs) is reviewed. We describe a study to clarify the relationship between NPSA and PA. METHOD: Thirty consecutive male respondents to an advertisement (PA: N = 15; NPSA: N = 15) were evaluated. The frequency of sexual behaviors, total sexual outlet, intensity of sexual desire, time spent in unconventional sexual behaviors, and a total sexual interest ratio were measured. Group differences were statistically examined using the Fisher's exact probability test (one tailed). Concomitant psychological, social, work, financial, legal, and medical sequelae were ascertained. RESULTS: The most prevalent lifetime sexual behaviors in both groups were NPSAs, especially compulsive masturbation, ego-dystonic promiscuity, and dependence on pornography. Mean total sexual outlet in both groups was approximately three times that of a comparable "normal" male sample. Components of total sexual outlet were reported in a nonnormative distribution pattern, and NPSA/PA sexual behaviors eclipsed conventional sexual activities in all measures. Group differences in measures of sexual behavior frequency, intensity, and time consumed by these behaviors were not statistically significant. CONCLUSION: The cormorbid presence of multiple NPSAs in 93% of the paraphilic men accompanied by comparable sexual and psychosocial sequelae suggests that NPSAs may represent a culturally adapted form of psychopathology that can also be manifested as PAs. A definition of hypersexual desire is offered, and a relationship between hypersexual desire and unconventional sexual outlet is suggested. PMID- 1429474 TI - Fluoxetine treatment of nonparaphilic sexual addictions and paraphilias in men. AB - BACKGROUND: Paraphilias (PAs) and non-paraphilic sexual addictions (NPSAs) may be behaviors that share a common perturbation of central serotonin neuroregulation as a component of their pathophysiology. Fluoxetine was selected as an agent that might mitigate these behaviors, based on the observations that PAs and NPSAs are associated with depression, compulsion, impulsivity, and disinhibited aggression. METHOD: Twenty men (PA, N = 10; NPSA, N = 10) recruited through newspaper advertisement were evaluated for depression and sexual behaviors at baseline and 4-week intervals while receiving fluoxetine pharmacotherapy in an open trial. Sixteen men completed the drug trial. Outcome was determined at 12 weeks using a single-factor, repeated-measures design and an analysis of variance. The general linear models procedure was used to test each of nine dependent measures. RESULTS: Nineteen (95%) of 20 men met non-exclusionary DSM-III-R criteria for dysthymia and 11 men (55%) met criteria for current major depression. At baseline, the paraphilic and the nonparaphilic subgroups were comparable in most intergroup measures of sexual function except total sexual outlet. PAs shared extensive comorbidity with NPSAs (100%). At outcome, statistically significant effects (p < .05) of fluoxetine were found in both groups over time for all variables pertaining to depression and PA/NPSA sexual behaviors. Statistically significant reduction in PA/NPSA response was evident by Week 4, while conventional sexual behavior was not adversely affected by pharmacotherapy. CONCLUSION: Men seeking treatment for PAs/NPSAs reported current depressive symptoms accompanied by a positive history of mood disorders, especially dysthymia and major depression. Fluoxetine selectively reduced both PA and NPSA behaviors in men reporting the presence of mild-severe depressive symptoms. Treatment response of PAs/NPSAs at outcome was independent of baseline depression score. Enhancement of central serotonin neurotransmission by fluoxetine may ameliorate symptoms of mood disorder, heightened sexual desire, and compulsivity/impulsivity associated with these conditions. PMID- 1429475 TI - Gradual versus rapid dawn simulation treatment of winter depression. AB - BACKGROUND: Bright light therapy has been shown to be effective in treating winter depression. Dawn simulation, a low-illuminance light that gradually increases in intensity while the person sleeps, decreased depression in an uncontrolled study. The present study compares a gradual dawn signal with a hypothesized placebo condition, a rapid dawn signal. METHOD: In a 4-week, randomized crossover design, nine patients with winter depression were treated with a gradual, 2.5-hour dawn simulation for 1 week and a rapid, 10-minute dawn simulation for 1 week. Both dawns had a maximum illuminance of 275 lux. At the end of each baseline week and treatment week, blind raters assessed the level of depression. RESULTS: Hamilton Rating Scale for Depression mean scores significantly decreased for both the gradual dawn (17.7 to 5.9, p < .05) and the rapid dawn (17.2 to 7.0, p < .05) condition. The improvement was similar for both treatments. Early morning awakening was significantly (p < .01) more common with the gradual dawn (7/9) than with the rapid dawn (1/9) condition. CONCLUSION: Depression decreased under both dawn simulations. Because the degree of improvement was similar, a placebo effect rather than the efficacy of dawn simulation might explain the results. However, a mere placebo effect is an unlikely explanation. The degree of improvement was similar to that shown in studies of bright light therapy and clearly superior to previous "placebo" control conditions. The side effects from the gradual dawn may have obscured a potential superiority of the gradual dawn over the rapid dawn. PMID- 1429476 TI - Psychiatric comorbidity and suicidality among intravenous drug users. AB - BACKGROUND: Prevalence of lifetime psychiatric comorbidity and history of attempted suicide among intravenous drug users was investigated. METHOD: One thousand sixty-two relatives of hospitalized alcoholics, felons, and control subjects were administered a structured interview that gathered data on lifetime psychiatric symptoms and psychoactive drug use. Psychiatric diagnoses were based on interview information, medical records, and family history data. Comparisons were made between 411 subjects who used no illicit drugs, 329 cannabis users, 230 subjects who had used psychoactive drugs other than cannabis more than five times but had never injected drugs, and 92 intravenous drug users. RESULTS: Any history of injecting drugs increased the odds of being diagnosed with antisocial personality disorder by a factor of 21.01, alcoholism by 4.42, and unipolar depression by 3.02. A diagnosis of antisocial personality disorder increased the odds of having injected drugs by a factor of 27.19, while diagnoses of alcoholism or unipolar depression conveyed odds for injecting drugs of 4.62 and 3.70, respectively. Intravenous drug use was associated with an 8.27-fold increase in odds for a suicide attempt compared with no drug use. CONCLUSION: Rates of alcoholism, depression, and antisocial personality disorder, but not other psychiatric disorders (other than drug dependence), are significantly elevated in intravenous drug users. Moreover, among drug users, the decision to inject is differentially made by those with antisocial personality disorder. A history of suicide attempt is common among intravenous drug users, but injecting appears to convey little additional risk above substantial but non-intravenous drug use. PMID- 1429477 TI - Potassium supplementation in lithium patients: a timely intervention or premature speculation? AB - BACKGROUND: Preventing and/or treating renal and other complications of long-term lithium therapy remains a challenge to clinicians. A review of studies in animals and anecdotal reports in humans suggests that potassium may have therapeutic value in this regard. METHOD: The Lithium Information Center data base of over 20,000 articles was searched under the title and subject heading of "potassium." Pertinent articles from the 303 references obtained served as the basis for this review. RESULTS: Studies in rats found that dietary potassium supplementation reduced adverse effects of lithium on growth and renal function and morphology. Loss of intracellular potassium may contribute to lithium-induced electrocardiographic ST-T wave changes. Little work has been done in humans to evaluate the potential benefit of potassium supplementation. CONCLUSION: Hypokalemia should be avoided or corrected in patients taking lithium. The role of potassium supplementation in preventing renal and other complications in the presence of normokalemia requires further investigation. PMID- 1429478 TI - Tricyclic antidepressant triggers mania in patient with organic affective disorder. PMID- 1429479 TI - Carbamazepine-associated thrombocytopenia. PMID- 1429480 TI - A fluvoxamine-induced frontal lobe syndrome in a patient with comorbid Gilles de la Tourette's syndrome and obsessive compulsive disorder. PMID- 1429481 TI - A case of early-onset Pick's disease. PMID- 1429482 TI - Acute tryptophan depletion: a method of studying antidepressant action. AB - Serotonin (5-HT) has been implicated in the pathophysiology of depressive syndromes and in the mechanism of antidepressant drug action. Rapid dietary depletion of tryptophan (TRP) provides a paradigm for studying the role of 5-HT in depressed patients. Drug-free depressed patients do not show mood changes during TRP depletion but about one third have a clinically apparent, transient improvement in mood on return to normal TRP intake. Depressed patients in clinical remission after 6 to 8 weeks of antidepressant therapy experience a transient depressive relapse during acute TRP depletion. The significance of these findings will be discussed. Tryptophan depletion in other psychiatric syndromes will also be reviewed. PMID- 1429483 TI - Basic advances in serotonin pharmacology. AB - Several advances in serotonin pharmacology have implications for psychiatry. The introduction of selective inhibitors of serotonin uptake into clinical use has established more firmly the relevance of brain serotonin neurons to depressive illness and is permitting an exploration of other therapeutic consequences of amplifying serotonergic function. A recent major advance in basic pharmacology has been the definition and characterization of multiple serotonin receptor subtypes in brain. Highly selective agonists and antagonists at these receptor subtypes are being developed as candidate drugs for therapy and as pharmacologic probes for assessing functionality of brain serotonin neurons in disease. Improved pharmacologic specificity will provide better tools for eliciting measurable responses mediated by brain serotonin receptors and for imaging key presynaptic and postsynaptic constituents of serotonin neuronal systems. Advances in serotonin pharmacology should therefore expand our understanding of serotonin's roles as a brain neurotransmitter in health and disease and lead to improved therapeutic agents. PMID- 1429484 TI - Serotonin activity in psychotic (delusional) major depression. AB - Psychotic (delusional) major depression is a distinct syndrome with marked morbidity. Previous studies have emphasized the role that glucocorticoids and dopamine may play in the pathogenesis of the disorder as well as in its response to treatment. In addition to reviewing data on these two systems, the possible role serotonin (5-HT) may play is also reviewed. Studies indicate increased 5-HT reuptake into platelets and elevated cerebrospinal fluid levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) are found in patients with this disorder. In addition, amoxapine, a four-ringed antidepressant with 5-HT2 antagonistic properties, has been reported to be effective in treating patients with this disorder. The implications of these findings vis-a-vis a role for serotonin in delusional major depression are discussed. Future studies on serotonin as well as on 5-HT2 antagonists in delusional depression are warranted. PMID- 1429485 TI - Serotonergic antidepressants and their efficacy in obsessive compulsive disorder. AB - Since 1985, major advances have been made in the pharmacologic treatment of obsessive compulsive disorder. Clomipramine is undoubtedly effective. Other selective serotonin reuptake inhibitors, such as fluvoxamine and sertraline, seem effective as well. Fluoxetine's efficacy has been principally based on convincing open-label studies and clinical practice. No large controlled studies have been published. A preliminary analysis of a double-blind trial in which 51 obsessive compulsive disorder patients were randomly assigned to either placebo or three fixed doses of fluoxetine reveals that the drug is decisively helpful. Unexpectedly, the 20-mg/day dose was as effective as the 40- or 60-mg/day dose. Although these findings further advance our understanding of short-term pharmacologic treatments, few data are available regarding maintenance doses, relapse, and efficacy of adjunctive treatments. PMID- 1429486 TI - Therapeutic apheresis in Canada. The Canadian Apheresis Study Group. PMID- 1429487 TI - Collection of blood mononuclear cells by leukapheresis for transplantation in a Yucatan miniature swine model. AB - A large animal model is needed to evaluate new apheresis technologies. These technologies include novel methods of harvesting the blood mononuclear cell population which contains the hematopoietic stem cells needed to restore hematopoiesis in recipients of hematopoietically lethal therapy and the use of cytokines to provide a safe and predictable method of manipulating these circulating hematopoietic stem cells. We describe the methods used to collect mononuclear cells by leukapheresis from Yucatan miniature swine. These animals are of sufficient size to tolerate the procedures and have many physiologic and hematologic similarities to man. They are of good temperament and are easily trained. Long-term venous access was obtained using single lumen silicone rubber catheters placed in the inferior vena cava. The animals were apheresed while fully awake using a Haemonetics Model V50 machine and a modified lymphocyte collection protocol. The procedure was highly efficient for the collection of mononuclear cells and a 10 pass procedure yielded a product which contained 19.7 x 10(9) mononuclear cells, 10.7 x 10(9) granulocytes, and 17 ml of erythrocytes in a volume of approximately 100 ml. This product can be cryopreserved and used for subsequent transplantation. The content of four apheresis procedures provides hematopoietic reconstitution of lethally irradiated swine on a time scale equivalent to transplantation of optimal numbers of bone marrow cells. PMID- 1429488 TI - Three years with a national apheresis registry. AB - The large number of unsolved problems in plasma exchange therapy makes an apheresis registry appear useful. The results of such an open prospective observational study from 1987 to 1989 in East Germany are presented in this paper. With 1,945 procedures in a total of 419 patients (on average 4.1 treatments per patient) about 80% of all treatments in the country were registered. Exchange volume averaged 2.7 (+/- 0.78) l or 43 (+/- 13.9) ml/kg body weight. Substitutes were albumin (51% of the cases), FFP (22%), and both (22%). Nephrological (25%) and neurological (23%) diagnoses prevailed among the treated diseases. Haematologic diseases (12%) were underrepresented and hepatic coma (20%) was overrepresented. Minor side effects occurred in 22% of all treatments and severe complications in 38 treatments (2%). Four fatalities probably resulted from plasmapheresis therapy. The registry permits an assessment of the treatment results and of several trends during the period of observation. PMID- 1429489 TI - Ten years experience with therapeutic apheresis in a community hospital. AB - A retrospective study was carried out on 2,500 therapeutic hemapheresis procedures performed at a community teaching hospital from 1980 to 1990. Seventy six percent of the procedures consisted of plasmapheresis (PE). The most frequently treated conditions were myasthenia gravis (MG), Guillain-Barre syndrome (GB), hyperviscosity (HV), and thrombotic thrombocytopenia purpura (TTP). Therapeutic results and clinical implications for these four conditions are discussed. PMID- 1429490 TI - Plasma exchange versus an affinity column for cholesterol reduction. AB - The recent introduction of low-density lipoprotein (LDL)/very low-density lipoprotein (VLDL) selective-removal systems offers an alternative to plasma exchange (PE). For the last 10 years, we have treated a male homozygous hypercholesterolemia type IIA patient with PE using 5% normal serum albumin (NSA) replacement, PE using 6% hydroxyethyl starch (HES) replacement, single dextran sulfate cellulose bead affinity column (DSAC) (Kaneka LA-40), and double DSAC. This report compares the performance of these systems in cholesterol reduction (total, LDL+VLDL, and high-density lipoprotein [HDL] and their effect on the total protein, albumin, and hematocrit levels. The number of procedures and average volume of plasma treated using PE-NSA, PE-HES, 1-DSAC, and 2-DSAC were 113, 64, 15, 90 and 3,939, 3,270, 3,519, and 3,588 ml, respectively. The average pretreatment total cholesterol levels were baseline 864 mg/dL, PE-NSA 606 mg/dL, PE-HES 610 mg/dL, 1-DSAC 467 mg/dL, and 2-DSAC 395 mg/dL with plasma reductions of 59%, 57%, 47%, and 55%, respectively. Average LDL+VLDL plasma reductions were PE-NSA 58%, PE-HES 59% (N = 1), 1-DSAC 46%, and 2-DSAC 56%. Average HDL plasma reductions were PE-NSA 58%, PE-HES 69% (N = 1), 1-DSAC 5%, and 2-DSAC 17%. The average total cholesterol and LDL+VLDL reductions were comparable for both types of PE and the 2-DSAC system. The average HDL loss was 53% lower for the DSAC systems than for PE systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429491 TI - An unexpected complication following immunoadsorption with a staphylococcal protein A column. AB - Extracorporeal immune adsorption with staphylococcal protein A (SPA) columns can remove immune complexes and immunoglobulins in the treatment of a variety of diseases. We present the case of an elderly man with neuropathy associated with monoclonal gammopathy, treated by 3 on-line SPA procedures. At the completion of these treatments his neuropathy relapsed, progressing to near-total paralysis. Return to a baseline clinical status required several months. The reason for this severe relapse is not clear. Possible explanations include SPA activation of T lymphocytes, with release of gamma interferon and increased antigen recognition, or removal of an antiidiotype control mechanism. We advise caution in the application of immunoadsorption to conditions in which it has not yet been evaluated. PMID- 1429492 TI - Donor reactions during DDAVP-stimulated plasmapheresis. AB - Donor exposure can be strikingly reduced for patients with classical hemophilia A and von Willebrand's disease when large volumes of potent cryoprecipitated AHF are prepared from donors following DDAVP (1-deamino-8-D-arginine vasopressin) stimulation and automated plasmapheresis--a procedure called "plasma exchange donation." Although this procedure has been reported to be relatively safe for donors, data are limited. Accordingly, we studied 20 donors during 48 procedures using DDAVP (0.3 micrograms/kg IV) followed by 2-3 L plasma collection. Replacement fluid for each initial plasma exchange donation was plasma protein fraction; autologous cryoprecipitate-poor plasma was used for subsequent procedures. Mild reactions, particularly facial flushing, were noted in all 48 procedures. No procedure was discontinued, but four were modified due to either an increased pulse rate (> or = 20/min from baseline) or a fall in systolic or diastolic blood pressure (> or = 20 mm Hg from baseline). No donor was deferred or withdrew from the program. Based on our modest experience, DDAVP stimulated plasma exchange donation appears to be a safe and effective method for collecting large quantities of plasma from which potent cryoprecipitated AHF can be prepared. PMID- 1429493 TI - Selective removal of anti-acetylcholine receptor antibody in the low temperature operation of membrane plasma fractionation. AB - The removal of anti-acetylcholine receptor antibody (anti-AChR Ab) by the plasma fractionator, Kuraray EVAL 2A, was measured as a function of the filtration temperature (4 and 37 degrees C). Plasmas procured from eight myasthenia gravis (MG) patients undergoing routine plasma exchanges (PE: membrane plasma filtration: n = 4, and centrifugation: n = 4) were used in the studies. Plasma flow rate was 20 ml/min, and plasma perfusion in single pass was terminated when the transmembrane pressure of the filter reached 300 mm Hg. Solute concentration data from before and after perfusion were used to assess the sieving coefficient (SC) of each solute. Results show that the SCs for anti-AChR Ab and albumin were significantly (P < .0002) lower at 4 degrees C (0.15 and 0.52, respectively) as compared to 37 degrees C (0.44 and 0.72, respectively). The SC of anti-AChR Ab (0.15) was significantly lower than the SC of IgG (0.42; P < .006) at 4 degrees C, even though it also belongs to the IgG class. The ratio of the SC of anti-AChR Ab to albumin at 4 degrees C (0.29) was significantly lower than that at 37 degrees C (0.57; P < .003). These data indicate that the selectivity of removal of anti-AChR Ab from albumin is higher at 4 degrees C than that at 37 degrees C. The volume treated at 4 degrees C was significantly lower than that treated at 37 degrees C, and it was less than that required for a clinical treatment; however, it was shown that filter backwashing is possible without loss of solute removal selectivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429494 TI - Backwashing procedure for on-line reuse of a plasma fractionator in cryofiltration. AB - During membrane plasma fractionation therapy there are reported incidences of membrane plugging requiring the corrective actions of either filter replacement or backwashing (BW) in order to continue the treatment. In this preliminary study, a simple BW procedure to allow for on-line reuse of the filter (Asahi AP06M) during the treatment was evaluated to assess its efficacy and safety in cryofiltration (CF). Evaluations were carried out on two patients treated for rheumatoid arthritis. Seven tests, each using 1 L or 2 L warmed saline as a BW solution were performed to evaluate the decrease of the transmembrane pressure (TMP) between just before and after backwashing and TMP change during cryofiltration procedures between before and after backwashing. Sieving coefficients of total protein, albumin, immunoglobulins (G, M, A), fibrinogen, and rheumatoid factor were also calculated at 1,000 ml plasma volume processed. Results showed statistically significant decreases of TMP from 300 mm Hg to 70 mm Hg between just before and after both backwashing procedures, and that there were no significant changes in the TMP increase during the cryofiltration procedure between pre- and post-BW. The protein sievings were not significantly affected by BW. The use of a second liter for rinsing did not reduce the inlet pressure further suggesting that 1 L BW was adequate. The accumulated solutes did not affect significantly the effective mean pore size. The BW procedure did not affect the overall patient safety during therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429495 TI - Apheresis for severe malaria complicated by cerebral malaria, acute respiratory distress syndrome, acute renal failure, and disseminated intravascular coagulation. AB - Malaria has become a very uncommon disease in Italy. Recently a variety of circumstances, such as travel to tropical countries as well as immigration from Asia and Africa, have combined to increase the number of malaria cases recorded annually. In this report we describe the use of red cell exchange transfusion and plasma exchange in the treatment of a patient with hyperparasitemic malaria (51% erythrocytes or more parasitized). When first observed the patient was in shock and had signs of cerebral malaria, disseminated intravascular coagulation, and acute respiratory distress syndrome, which in the following 2 days were complicated by acute renal failure. After mefloquine therapy combined with 3 red blood cell exchanges, 2 plasma exchanges, and 10 dialysis sessions over 14 days, the patient recovered completely. This case of severe malaria with multiple complications, treated with mefloquine in conjunction with both exchange transfusion and plasmapheresis, had a successful outcome and lends further support to the possible beneficial role of exchange transfusion in complicated malaria. PMID- 1429496 TI - Simplified blood access method for immunoadsorption. PMID- 1429497 TI - Vanadate stimulates D-glucose transport into sarcolemmal vesicles from rat skeletal muscles. AB - Vanadate is known to have various insulin-like actions including activation of D glucose uptake into the skeletal muscle and adipose tissue. In this study, we examined the effect of orthovanadate on D-glucose uptake into sarcolemmal vesicles prepared from rat hind limb skeletal muscles. In the presence of 10 mM vanadate, the initial rate of D-glucose uptake into sarcolemmal vesicles was enhanced 4-5 times above the basal value. Half-maximal concentration for this effect of vanadate was 3 mM. The D-glucose uptake was also stimulated by metavanadate, but not by selenite, selenate, or molybdate. When vanadate was removed from the vesicles by dilution and centrifugation, D-glucose uptake into the vesicles returned to the basal level, indicating that the effect of vanadate was reversible. Saturation curves showed that the Vmax value for the D-glucose uptake was enhanced more than 4-fold by 10 mM vanadate. Therefore, the activation of D-glucose uptake was due, at least in part, to a large increase in the Vmax value. These results suggest that vanadate increases the intrinsic activity (turnover number) of skeletal muscle glucose transporters in a reversible manner. PMID- 1429498 TI - Amino acid sequence and disulfide-bridge location of canine haptoglobin. AB - The complete amino acid sequence and disulfide-bridge location of canine haptoglobin (Hp) were determined by analyzing various fragments produced chemically and/or enzymatically. Canine Hp consists of two light (L) and two heavy (H) chains with 83 and 245 amino acid residues, respectively. It has three potential oligosaccharide-binding sequences, Asn-X-Ser/Thr, one in the L chain and two in the H chain. All of them are glycosylated. Comparison of the amino acid sequences between canine Hp and human Hp shows 68 and 85% homology for L chains and H chains, respectively. About 20% of the canine L chain still retains a carboxyl-terminal arginine residue, which is completely removed during maturation in human L-chain. The half-cystine residue at position 15 in the L chain, which participates in the inter-L chain disulfide bridging in human Hp, has been replaced by a leucine residue in canine Hp. Therefore, an LH unit in canine Hp may be joined to another LH unit by a noncovalent (mainly hydrophobic) interaction to form the complete molecule. The disulfide bridges in canine Hp link Cys-34L to Cys-68L, Cys-72L to Cys-105H, Cys-148H to Cys-179H, and Cys-190H to Cys-220H, as in the case of human Hp. PMID- 1429499 TI - Hepatic triiodothyronine sulfation and its regulation by growth hormone and triiodothyronine in rats. AB - The regulatory mechanism of cytosolic sulfation of T3 has been studied in rat liver. Sulfation of T3 is sexually differentiated in adult rats of Sprague-Dawley (SD), Fisher 344, and ACI strains. In SD strain, the male animals showed 4 times higher sulfating activity than did the females. The specific activity was decreased by hypophysectomy of male adult rats, but was not affected in the females. Thus, the sex-difference was abolished in the hypophysectomized condition. Supplement of human GH intermittently twice daily for 7 days, to mimic the male secretory pattern, increased T3 sulfating activity in both sexes of hypophysectomized rats, whereas continuous infusion to mimic a female secretory pattern had no appreciable effect. Cytosolic sulfation of T3 was decreased by 25 to 30% by thyroidectomy or propylthiouracil treatment of male adult rats, and was restored by the supplementation of T3 (50 micrograms/kg daily for 7 days) to thyroidectomized rats. Administration of T3 in hypophysectomized rats almost completely restored the sulfating activity in the males and increased the activity in the females. Cytosolic T3 sulfation was inhibited by the addition of known inhibitors of phenol sulfotransferase, pentachlorophenol or 2,6-dichloro-4 nitrophenol. These results indicate a role of pituitary GH in hepatic sulfation of thyroid hormones in rats. The data obtained also raise the possibility that GH may modify the effect of thyroid hormones on the pituitary by a feed-back mechanism through changing the level of a sex-dominant phenol sulfotransferase(s) in rat livers. T3 was also sulfated in hepatic cytosols of mouse, hamster, rabbit, dog, monkey, and human.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429500 TI - Release of O-linked sugar chains from glycoproteins with anhydrous hydrazine and pyridylamination of the sugar chains with improved reaction conditions. AB - A method for preparation of pyridylamino (PA-) derivatives of O-linked sugar chains from glycoproteins was developed. A glycopeptide containing O-linked Gal beta 1-3GalNAc was prepared from fetuin and treated with anhydrous hydrazine followed by N-acetylation of free amino groups. Sugar chains released were pyridylaminated with improved reaction conditions and excess reagents were removed by gel filtration. Gal beta 1-3GalNAc-PA obtained together with PA-Gal as a by-product was quantified by HPLC. Conditions for the hydrazine treatment were investigated and the treatment at 40 degrees C for 350 h gave the best results for releasing O-linked sugar chains. The total yield of Gal beta 1-3GalNAc-PA from the glycopeptide was 53% under the established conditions and that of PA-Gal was 18%. The present method was applied to a glycoprotein, and the expected PA-O linked sugar chains were obtained. Under these conditions, N-linked sugar chains were also released. PMID- 1429501 TI - Evidence for a single catalytic site of honeybee alpha-glucosidase I by chemical modification with diethylpyrocarbonate. AB - Honeybee alpha-glucosidase I was inactivated with diethylpyrocarbonate (DEPC). The inactivation followed pseudo-first-order kinetics. The rate of the loss of activity was decreased by the addition of a substrate, maltose. Since there was no spectral change in the tyrosine absorption region, it was recognized that DEPC did not react with this residue. The alpha-glucosidase had one free sulfhydryl group, which was not involved in the catalytic reaction, and was not modified by DEPC. On the other hand, the specific reaction of DEPC with a histidyl residue was spectrophotometrically confirmed by an increase in absorption near 240 nm, and the activity of the inactivated enzyme was restored by hydroxylamine. The modification rate of one histidyl residue by DEPC was almost equal to the rate of the activity loss. These results indicate that there is one histidyl residue at or near the catalytic site, and that honeybee alpha-glucosidase I has a single active site. PMID- 1429503 TI - The interaction of elderberry (Sambucus sieboldiana) bark lectin and sialyloligosaccharides as detected by 1H-NMR. AB - The interaction of Japanese elderberry bark lectin (Sambucus sieboldiana agglutinin, SSA) with carbohydrate was investigated by 1H-NMR. When a low affinity ligand, methyl beta-D-galactoside (beta MeGal), was mixed with SSA, each proton signal of beta MeGal was broadened. The signal of H-4 was markedly broad, while those of H-1, OCH3, and H-2 of beta MeGal were rather sharp. The specific broadening of Gal H-4 was more evident when SSA was mixed with methyl-beta-D lactoside (beta MeLac). Position-dependent signal broadening suggests that beta MeGal binds to SSA such that H-4 is closely involved in the contact region, but H 1, OCH3, and H-2 are far from this region. In the case of a high affinity ligand, Neu5Ac(alpha 2-6)Gal(beta 1-4)Glc(= N6L), ligand signals of the SSA-N6L mixture did not change at all. But when a small amount of N6L was added to the SSA-beta MeGal mixture, the broad signals of bound beta MeGal became dramatically sharp. This indicates that the added N6L molecules liberated the bound beta MeGal from SSA. On the other hand, the sialyllactose with the alpha(2-3)-linkage(= N3L) could not substitute for bound beta MeGal because of its lower affinity. This demonstrates that the competitive binding experiment between two ligands is a useful technique to detect the interaction of lectins with high affinity ligands which could not be observed directly by NMR signal broadening and/or chemical shift change. PMID- 1429502 TI - Evidence that three histidine residues of a base non-specific and adenylic acid preferential ribonuclease from Rhizopus niveus are involved in the catalytic function. AB - In order to study the structure-function relationship of an RNase T2 family enzyme, RNase Rh, from Rhizopus niveus, we investigated the roles of three histidine residues by means of site-specific mutagenesis. One of the three histidine residues of RNase RNAP Rh produced in Saccharomyces cerevisiae by recombinant DNA technology was substituted to a phenylalanine or alanine residue. A Phe or Ala mutant enzyme at His46 or His109 showed less than 0.03%, but a mutant enzyme at His104 showed 0.54% of the enzymatic activity of the wild-type enzyme with RNA as a substrate. Similar results were obtained, when ApU was used as a substrate. The binding constant of a Phe mutant enzyme at His46 or His109 towards 2'-AMP decreased twofold, but that at His104 decreased more markedly. Therefore, we assumed that these three histidine residues are components of the active site of RNase Rh, that His104 contributes to some extent to the binding and less to the catalysis, and that the other two histidine residues and one carboxyl group not yet identified are probably involved in the catalysis. We assigned the C-2 proton resonances of His46, His104, and His109 by comparison of the 1H-NMR spectra of the three mutant enzymes containing Phe in place of His with that of the native enzyme, and also determined the individual pKa values for His46 and His104 to be 6.70 and 5.94. His109 was not titrated in a regular way, but the apparent pKa value was estimated to be around 6.3. The fact that addition of 2'-AMP caused a greater effect on the chemical shift of His104 in the 1NMR spectra as compared with those of the other histidine residues, may support the idea described above on the role of His104. PMID- 1429504 TI - Molecular evolution of phosphoenolpyruvate carboxylase for C4 photosynthesis in maize: comparison of its cDNA sequence with a newly isolated cDNA encoding an isozyme involved in the anaplerotic function. AB - Molecular events associated with the evolution of an enzyme for C4 photosynthesis were investigated. In maize, at least three isozymes of phosphoenolpyruvate carboxylase [EC 4.1.1.31] are known: the C4-form, the C2-form and the root-form, being named according to their physiological roles and pattern of tissue distribution [Ting, I.P. & Osmond, C.B. (1973) Plant Physiol. 51, 448-453]. A cDNA clone which presumably encodes the C3-form isozyme was newly isolated and analyzed. Comparison of the sequences of the C3-form and C4-form isozymes revealed that (i) the homologies in the nucleotide and deduced amino acid sequences were 71 and 77%, respectively, and (ii) the gene for the C4-form isozyme evolved under strong G/C pressure. The genes for these isozymes were found to be located apart on different chromosomes. A phylogenetic tree was constructed using 8 amino acid sequences of phosphoenolpyruvate carboxylases from various sources. The topology of the tree indicated that, at least in monocots such as maize and sorghum, the genes for the C4-form and C3-form isozymes diverged from their common ancestral gene earlier than the monocot-dicot divergence (about 2 x 10(8) yr ago), though the divergence of maize (C4 plant) from wheat (C3 plant) is supposed to have occurred much later (6 x 10(7) yr ago). PMID- 1429505 TI - Further studies on chimeric P450 2C2/2C14 having testosterone 16 beta-hydroxylase activity which is absent in the parental P450s. AB - cDNAs for various chimeras between P450 2C2, P450 2C14, P450 2B5, and P450 2E1 were constructed, the chimeric P450s were expressed in yeast cells, and their catalytic activities were compared in the reconstituted system containing partially purified P450 preparations. The chimera P450(2Hc3), consisting of the 462 amino-terminal residues of P450 2C2 and the remaining 28 residues of P450 2C14, had testosterone 16 beta-hydroxylase activity, which is not seen in either of the parental P450s, in addition to higher activities of laurate (omega-1) hydroxylation and benzphetamine N-demethylation than the parental P450s [Uno, T. et al. (1990) Biochem. Biophys. Res. Commun. 167, 498-503]. When either of the segments from P450 2C2 and P450 2C14 in this chimera was replaced with the corresponding sequences of P450 2E1 or when the 35 carboxy-terminal residues of P450(2Hc3) were replaced with those of P450 2B5, the 16 beta-hydroxylase activity disappeared. When the 262 amino-terminal residues, except for residues 90-125 (region 90-125), of P450(2Hc3) were replaced with those of P450 2C14, the resulting chimera retained both testosterone 16 beta- and laurate (omega-1) hydroxylase activities. Further replacing the region 90-125 with that of P450 2C14 resulted in disappearance of the 16 beta-hydroxylase activity and profound decrease in the (omega-1)-hydroxylase activity. Testosterone 16 beta hydroxylation was inhibited by laurate and laurate (omega-1)-hydroxylation by testosterone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429506 TI - Thermostable, salt tolerant, wide pH range novel chitobiase from Vibrio parahemolyticus: isolation, characterization, molecular cloning, and expression. AB - A chitobiase gene from Vibrio parahemolyticus was cloned into plasmid pUC18 in Escherichia coli strain DH5 alpha. The plasmid construct, pC120, contained a 6.4 kb Vibrio DNA insert. The recombinant gene expressed chitobiase [EC 3.2.1.30] activity similar to that found in the native Vibrio. The enzyme was purified by ion exchange, hydroxylapatite and gel permeation chromatographies, and exhibited an apparent molecular weight of 80 kDa on SDS-polyacrylamide gel electrophoresis. Chitobiose and 6 more substrates, including beta-N-acetyl galactosamine glycosides, were hydrolyzed by the recombinant chitobiase, indicating its putative classification as an hexosaminidase [EC 3.2.1.52]. The enzyme was resistant to denaturation by 2 M NaCl, thermostable at 45 degrees C and active over a very unusual (for glycosyl hydrolases) pH range, from 4 to 10. The purified cloned chitobiase gave 4 closely focussed bands on an isoelectric focusing gel, at pH 4 to 6.5. The N-terminal 43 amino acid sequence shows no homology with other proteins in commercial databanks or in the literature, and from its N-terminal sequence, appears to be a novel protein, unrelated in sequence to chitobiases from other Vibrios reported and unrelated to hexosaminidases from other organisms. PMID- 1429507 TI - A soluble protease identified from rat kidney degrades endothelin-1 but not proendothelin-1. AB - Endothelin-1 (ET-1) is a potent peptidic vasoconstrictor. This peptide has been shown to be cleared rapidly by the kidney. The purpose of the present study was to assess the involvement of renal proteolytic enzymes in the clearance/degradation of ET-1. Incubation of ET-1 with the cytosolic fraction of rat kidney homogenate resulted in a decrease of contractile activity on rabbit aortic rings when compared to the untreated ET-1. This cytosolic fraction was chromatographed by anion-exchange and concanavalin A columns. The partially purified enzyme cleaved off the C-terminal tryptophan of ET-1 rapidly, resulting in a peptide which is three orders of magnitude weaker in potency than ET-1 in causing smooth muscle contraction. In contrast, proendothelin-1 was not degraded by this endothelin degradation enzyme (EDE). The effects of EDE on other vasoactive peptides were also examined. The C-terminal tyrosine of atrial natriuretic peptide was cleaved by EDE, but the biological activity of the resulting peptide was not significantly changed. Angiotensin II was not a substrate for EDE. The EDE was shown to be different from both carboxypeptidases A and B based on the HPLC analysis of the degradation products of ET-1 produced by these enzymes. In addition, these enzymes displayed different sensitivities toward a carboxypeptidase inhibitor from potato tuber. These results suggest that this previously unidentified enzyme inactivates ET-1 effectively and that it may play a role in modulating the levels of ET-1 in the kidney. PMID- 1429508 TI - Farnesyl diphosphate synthase and solanesyl diphosphate synthase reactions of diphosphate-modified allylic analogs: the significance of the diphosphate linkage involved in the allylic substrates for prenyltransferase. AB - Diphosphate-modified substrates for prenyltransferase were synthesized and examined as substrates for the prenyltransferase reaction. They were dimethylallyl methylenediphosphonate, geranyl methylenediphosphonate, geranyl imidodiphosphate, geranyl phosphosulfate, farnesyl methylenediphosphonate, farnesyl imidodiphosphate, and farnesyl phosphosulfate. All of them except dimethylallyl methylenediphosphonate were accepted as substrates by solanesyl diphosphate synthase to give solanesyl diphosphate and the former four analogs were also accepted as substrates by farnesyl diphosphate synthase to give farnesyl diphosphate. The Km values of both enzymes for the methylenediphosphonate and imidodiphosphate analogs were comparable to those of the corresponding diphosphate substrates, but the phosphosulfate analogs showed much greater Km values than the diphosphate substrates. On the other hand, the Vmax values for these artificial substrates were all smaller than those for the corresponding natural substrates. Kinetic experiments with the analogs showed that the ionization-condensation-elimination mechanism proposed for the farnesyl diphosphate synthase reaction holds also for the solanesyl diphosphate synthase reaction and that the diphosphoryl structure, capable of chelating with divalent cations, is important topologically and kinetically rather than thermodynamically. PMID- 1429509 TI - Synthetic reaction of Cellvibrio gilvus cellobiose phosphorylase. AB - The synthetic reactions of the cellobiose phosphorylase from Cellvibrio gilvus were investigated in detail. It was found that, besides D-glucose, some sugars having substitution or deletion of the hydroxyl group at C2 or C6 of the D glucose molecule could serve as a glucosyl acceptor, though less effectively than D-glucose. The enzyme showed higher activity with beta-D-glucose than with the alpha-anomer as an acceptor. This result indicates that it recognizes the anomeric hydroxyl group not involved directly in the reaction. beta-D-Cellobiose was also phosphorolyzed faster than the alpha-anomer. Substrate inhibition was observed with D-glucose, 6-deoxy-D-glucose, or D-glucosamine as an acceptor, with D-glucose being most inhibiting. This inhibition was studied in detail and it was found that D-glucose competes with alpha-D-glucose-1-phosphate for its binding site. A model of competitive substrate inhibition was proposed, and the experimental data fit well to the theoretical values that were calculated in accordance with this model. PMID- 1429510 TI - Chemical synthesis, molecular cloning, and expression of the gene coding for the Trichosanthes trypsin inhibitor--a squash family inhibitor. AB - The gene coding for a Trichosanthes trypsin inhibitor analog (Ala-6-TTI) in which methionine at position 6 was replaced by alanine was synthesized chemically. The synthetic gene was cloned into plasmid pWR590-1 and expressed in Escherichia coli as a fusion protein composed of beta-galactosidase fragment of 590 amino acid residues and (Ala-6)-TTI, with methionine as a connecting residue. After cyanogen bromide cleavage and reduction of the fusion protein, followed by refolding with trypsin-Sepharose 4B as a matrix and affinity chromatography on the immobilized enzyme, the fully active (Ala-6)-TTI was obtained. The trypsin inhibitory activity and amino acid composition of the recombinant (Ala-6)-TTI were consistent with those of the natural one. The (Ala-6)-TTI gene was also cloned into the secretion expression vector, pVT102U/alpha, in Saccharomyces cerevisiae. In order to make the reading frame of the gene compatible with the vector, a nucleotide was inserted into the (Ala-6)-TTI gene via site-directed mutagenesis. The secreted (Ala-6)-TTI was purified and found to be correctly processed at the junction between the alpha-factor leader peptide and (Ala-6)-TTI downstream. Of the two expression systems, the latter is more advantageous in the high yield (greater than 2 mg/liter), easy purification and needlessness of disulfide refolding. PMID- 1429511 TI - Novel structure of the N-acetylgalactosamine containing N-glycosidic carbohydrate chain of batroxobin, a thrombin-like snake venom enzyme. AB - The structure of the Asn-linked carbohydrate chain of batroxobin, a thrombin-like enzyme from Bothrops atrox moojeni snake venom, has been determined. The sugar chain was isolated from batroxobin by hydrazinolysis followed by pyridylamination (PA). The PA-oligosaccharide chain was purified by HPLC on an anion exchange or reverse phase columns, and its structure was examined by sequential exoglycosidase digestion, 600 MHZ 1H NMR spectroscopy and methylation analysis. The results indicate that the oligosaccharide chain has the following structure involving a novel linkage, NeuAc alpha 2----3GalNAc. PMID- 1429512 TI - A simple and efficient amplification method of DNA with unknown sequences and its application to microdissection/microcloning. AB - An alternative method for amplification of DNA with unknown sequences was developed. This involves the direct ligation of a primer oligodeoxyribonucleotide itself to restricted DNA fragments with unknown sequences to be amplified by PCR. The oligonucleotide need not be phosphorylated and need not be annealed with its complementary oligonucleotide in advance for ligation. The ligation reaction seems to be independent of the concentration of unknown DNA, proceeds in short time, and is efficient. The ligation efficiency was more than 30% at a low concentration, 10 fg/microliters, of DNA. This method was applied to a microdissection/microcloning of the short arm of human chromosome 2. Of 65 clones screened for the highly repetitive sequences with total human genomic DNA, eleven (17%) were positive. Their inserts ranged in size from 150 to 1,200 bp (average, 460 bp). In Southern blot analysis, thirty consecutive clones all detected signals common to both total human genomic DNA and mouse-human hybrid cell DNA containing only chromosome 2 of human origin. Among them, 24 (80%) were unique sequences, and 6 (20%) were multi-copy (or intermediate-repeat) sequences. Thus, this method is simple and efficient, and provides an alternative way to amplify unknown DNA. PMID- 1429513 TI - Evidence for conversion of human salivary alpha-amylase family A to family B by an enzyme action. AB - SDS-PAGE showed that human salivary alpha-amylase family A (HSA-A) was converted to family B (HSA-B) in human saliva. This conversion did not occur in the supernatant of saliva which had been centrifuged at 105,000 x g for 60 min. An enzyme which catalyzed the conversion existed in the insoluble fraction of human saliva. The enzyme was solubilized with nonionic or zwitterionic detergents, and showed the maximum activity around pH 6. It was stable between pH 4 and 10, and at a temperature lower than 40 degrees C. The enzyme reduced the molecular weight of HSA-A (62,000) to the same molecular weight (58,000) as that of HSA-B without forming any intermediate. It also changed the PAGE pattern of multiple forms of HSA-A to the same pattern as that of HSA-B. It was not inhibited by protease inhibitors, and it did not destroy the reactivity of HSA-A with anti-human salivary alpha-amylase antiserum. The enzyme diminished the reactivity of HSA-A with concanavalin A. These results indicate that HSA-A was converted to HSA-B through the release of sugar chains by the action of the enzyme in the insoluble fraction of human saliva. PMID- 1429514 TI - Nucleotide sequences and characterization of liv genes encoding components of the high-affinity branched-chain amino acid transport system in Salmonella typhimurium. AB - A 7.6-kb fragment of Salmonella typhimurium LT2 containing the liv gene cluster, which specifies the high-affinity branched-chain amino acid transport system (LIV I), has been isolated. The upstream region contains the livB and livC genes encoding the leucine-isoleucine-valine-threonine and leucine-specific binding proteins, respectively. In this study, the nucleotide sequence of the 4-kb downstream segment was determined and found to contain four reading frames, designated as livA, livE, livF, and livG, that encode putative membrane associated proteins. The livA and livE genes encode hydrophobic proteins composed of 308 and 425 amino acid residues, respectively. The livF and livG genes encode hydrophilic proteins of 255 and 237 amino acids, respectively; both the proteins contain consensus amino acid sequences found in proteins with ATP-binding sites. These four genes linked together have a potential rho-independent transcriptional terminator adjacent to the 3'-end of livG. No promoter sequence was found in the immediate upstream region of the livAEFG cluster. The livA, livE, livF, and livG gene products were identified as proteins with apparent M(r)s of 25,500, 34,500, 28,000, and 26,000, respectively, by SDS-polyacryl-amide gel electrophoresis. The deduced amino acid sequences of these four proteins showed strong homology to those of the corresponding membrane-associated proteins required for the high affinity branched-chain amino acid transport systems from both Escherichia coli and Pseudomonas aeruginosa. PMID- 1429515 TI - Detection of human urinary alpha-amylase encoded by the AMY2B gene using a fluorogenic substrate, FG5P. AB - The existence of alpha-amylase (HXA) encoded by alpha-amylase gene AMY2B in healthy humans was examined using a fluorogenic substrate, FG5P (FG-G-G-G-G-P: FG, 6-deoxy-6-[(2-pyridyl)amino]-D-glucose residue; G, glucose residue; P, p nitrophenyl residue; -, alpha-1,4-glycosidic bond). Chromatofocusing of urine from a healthy human was carried out. FG5P was digested with the fractions exhibiting alpha-amylase activity and each digest at an early stage was analyzed by HPLC. FG5P was hydrolyzed to FG3 (FG-G-G) and p-nitrophenyl alpha-maltoside (G G-P), and to FG4 (FG-G-G-G) and p-nitrophenyl alpha-glucoside (G-P). The molar ratios of FG4 to FG3 (FG4/FG3) in the digests with basic fractions were larger than those in the digests of human pancreatic alpha-amylase (HPA, 1.11) and human salivary alpha-amylase (HSA, 0.51). Considering that the value for the AMY2B gene product with yeast (yHXA) is 1.88, a value of more than 1.11 implies that HXA exists. The amount of HXA was determined after removal of HSA on an anti-human salivary alpha-amylase antibody bound column. The FG4/FG3 values for six urine samples free from HSA were 1.23-1.26. Assuming that the FG4/FG3 value for HXA is the same as that for yHXA, the ratios of HXA and HPA were estimated to be 1:5.4 4.1. The results obtained showed that the AMY2B gene is usually expressed as HXA in healthy humans. PMID- 1429516 TI - Expression in Escherichia coli and a functional study of a beta-troponin T 25 kDa fragment of rabbit skeletal muscle. AB - A 25 kDa fragment of beta-type troponin T (beta-TnT) was expressed in Escherichia coli, and its function as a component of the regulatory system for actomyosin ATPase was compared with that of the authentic counterpart, the full length alpha TnT. The expressed species, designated as beta-TnT(N'-208), consists of 208 residues. It lacks the entire variable region at the amino-terminus and, near the carboxyl-terminus, a segment of 14 residues is changed from the alpha-type to the beta-type sequence. Functional tests indicated that the truncated beta-TnT was not distinguishable from the full length alpha-TnT, suggesting that neither deletion of the variable N-terminal region nor alteration of the type has a significant effect on the regulatory action of TnT. PMID- 1429517 TI - Activation and stabilization of UDP-glucuronyltransferase by lysophosphatidylcholine. AB - Interactions between purified UDP-glucuronyltransferase from 3-methylcholanthrene treated rat liver microsomes (named GT-1) and lysophosphatidylcholine, which is essential for expression of GT-1 activity, were examined. Phospholipid-free GT-1, which could not express its full activity [Yokota et al. (1988) J. Biochem. 104, 531-536], was activated fully by addition of lysophosphatidylcholine (0.04 mM final concentration) into the assay medium. Lysophosphatidylcholine also protected GT-1 effectively against heat inactivation. Palmitoyllysophosphatidylcholine and stearoyllysophosphatidylcholine were most successful for the activation and stabilization of GT-1. On treatment of GT-1 with carboxypeptidase Y, the transferase was inactivated immediately, but the treatment in the presence of lysophosphatidylcholine affected the activity only a little. Lysophosphatidylcholine was also found to protect GT-1 against cleavage by carboxypeptidase Y. On treatment of GT-1 with trypsin or aminopeptidase T, the activity was lost and GT-1 protein could be digested even when lysophosphatidylcholine was present. It is suggested that UDP glucuronyltransferase forms an active and stable conformation, in which the carboxy-terminal region is protected against protease, with lysophosphatidylcholine. PMID- 1429518 TI - Biochemical and immunological characterization of the DNA binding protein (RBP-J kappa) to mouse J kappa recombination signal sequence. AB - We have investigated whether J kappa recombination signal sequence (RS) binding protein (RBP-J kappa) has any partial catalytic activities involved in the VDJ recombination reaction, such as cleavage, ligation, and bending of DNA. Murine RBP-J kappa protein purified by J kappa-RS affinity chromatography did not show DNA cleavage activities but contained a strong DNA ligase activity. To obtain a large amount of purified RBP-J kappa protein, recombinant RBP-J kappa was synthesized in Escherichia coli as a fusion protein and also in silkworm cells. Although recombinant RBP-J kappa produced in silkworm cells could bind J kappa RS, it failed to show either ligase or DNA bending activity. Since the DNA affinity-purified RBP-J kappa has the ligase activity, the RBP-J kappa protein may form a complex with a ligase in vivo. We have raised monoclonal antibodies against the RBP-J kappa fusion protein which was synthesized in E. coli and unable to bind J kappa-RS. Using the anti-RBP-J kappa monoclonal antibody we have shown that the RBP-J kappa protein is expressed ubiquitously in mammalian tissues. The ubiquitous expression of the RBP-J kappa protein is consistent with the hypothesis that the RBP-J kappa protein may have dual function [Furukawa et al. (1991) J. Biol. Chem. 266, 23334-23340]. PMID- 1429519 TI - Cell density-dependent regulation of albumin synthesis and DNA synthesis in rat hepatocytes by hepatocyte growth factor. AB - Hepatocyte growth factor (HGF), a potent mitogen for mature hepatocytes, has been considered to act as a hepatotropic factor for liver regeneration. We examined the effect of HGF on albumin synthesis and DNA synthesis of adult rat hepatocytes cultured at various cell densities. HGF stimulated albumin synthesis of hepatocytes by 40-60% when they were cultured at higher cell densities such that there was tight cell-cell contact. But at lower cell densities HGF failed to stimulate albumin synthesis. In contrast, the stimulatory effect of HGF on DNA synthesis of hepatocytes was more potent at lower than at higher cell densities: HGF did not stimulate DNA synthesis of hepatocytes cultured at confluent cell density. Thus, HGF seems to stimulate both albumin synthesis and DNA synthesis of hepatocytes, in a reciprocal relationship depending on cell density. When the effects of various cytokines were examined, epidermal growth factor, transforming growth factor-alpha, and acidic fibroblast growth factor also stimulated albumin synthesis by 20-30%. However, transforming growth factor-beta 1, basic fibroblast growth factor, and interleukin-1 beta had no effect on albumin synthesis, while interleukin-6 inhibited it by 42%. Thus HGF was the most potent in stimulating albumin synthesis in these cytokines. Since HGF is markedly increased in the liver or plasma following various liver insults, HGF may be involved in liver regeneration through the potential to stimulate both cell growth and liver specific functions such as albumin synthesis in a cell density-dependent manner. PMID- 1429520 TI - Effects of salts on thermolysin: activation of hydrolysis and synthesis of N carbobenzoxy-L-aspartyl-L-phenylalanine methyl ester, and a unique change in the absorption spectrum of thermolysin. AB - It has been reported that neutral salts such as NaCl activate the thermolysin catalyzed hydrolysis of substrates containing glycine at the P1 position (carboxylic side of the cleavage bond) [Holmquist, B. & Vallee, B.L. (1976) Biochemistry 15, 101-107]. In this paper, we demonstrate that high concentrations (1-4 M) of neutral salts greatly enhance the thermolysin activity in both hydrolysis and synthesis of N-carbobenzoxy-L-aspartyl-L-phenylalanine methyl ester (ZAPM), a precursor of a peptide sweetener, aspartame, in which the L aspartyl residue is the P1 residue. The enzyme activity is enhanced with an increase in salt concentration in a pseudo-exponential fashion. The degree of activation by salts was in the order LiCl > NaCl > KCl. The rate of ZAPM hydrolysis in the presence of 3.8 M NaCl was 6-7 times higher than that in its absence, and 50 times or more activation is expected in saturated NaCl solution. The activation is brought about solely through an increase in the catalytic constant (kcat), and the Michaelis constant (Km) is not affected at all by the presence of NaCl. On mixing thermolysin with NaCl, a unique absorption difference spectrum suggesting a conformational change of the enzyme was observed. The intensity increased in a pseudo-exponential fashion with increase of NaCl concentration up to 3 M, and this dependence is similar to that of the enzyme activity. PMID- 1429521 TI - Predicted secondary and tertiary structures of carp gamma-crystallins with high methionine content: role of methionine residues in the protein stability. AB - A systematic structural comparison of several carp gamma-crystallins with high methionine contents was made by the secondary-structure prediction together with computer model-building based on the established X-ray structure of calf gamma-II crystallin. The overall surface hydrophilicity profile and the distribution of helices, beta-sheets, and beta-turns along the polypeptide chains are very similar among these carp gamma-crystallins. In addition, their general polypeptide packing is close to the characteristic 2 domain/4 motif Greek key three-dimensional conformation depicted for the calf gamma-II crystallin. Interestingly, most hydrophobic methionine residues are located on the protein surface with only a few buried inside the protein surface or in the interface between two motifs of each domain. The exposed hydrophobic and polarizable methionine cluster on the protein surface may have a bearing on the crystallin stability and dense packing in the piscine species, and probably also provides a malleable nonpolar surface for the interaction with other crystallin components for the maintenance of a clear and transparent lens. PMID- 1429522 TI - Purification, analysis, and enzymatic activity of recombinant human synovial fluid phospholipase A2 and N-terminal variants. AB - Recombinant human synovial fluid phospholipase A2 (rPLA2) and several variants with N-terminal sequences modified by addition or deletion of one or two amino acid residues (ala or Met; Des-Asn1, Leu2) have been expressed in mammalian cells and in Escherichia coli, respectively, purified to homogeneity, and characterized. The observed values for the molecular mass of rPLA2 and variants are in complete agreement with the predicted values for a correctly folded structure containing seven disulfide bridges. Moreover, the relative proportions of the various types of secondary structures of the variants of rPLA2, as measured by CD spectroscopy, are similar to that found for native porcine pancreatic PLA2, indicating that the recombinant proteins are correctly folded. Enzymatic activities of rPLA2 with modified N-termini decreased to 1.3-0.005% of the activity of the mature rPLA2, emphasizing a key role of the N-terminus for catalytic activity. PMID- 1429523 TI - Studies on the uronic acid-containing glycoproteins of Fusarium sp. M7-1: IV. Isolation and identification of four novel oligosaccharide units derived from the acidic polysaccharide chain. AB - Four novel oligosaccharide units were isolated from the acetolysis products of the acidic polysaccharide chain derived from the glycoproteins of Fusarium sp. M7 1. Their chemical structures were resolved mainly by 1H-NMR spectrometry in combination with methylation analysis and mass spectrometry. The results indicate that these oligosaccharide units originated from the side chains, GlcNAc alpha 1- >4GlcA alpha 1-->2(GlcNac alpha 1-->4)GlcA alpha 1-->2Gal, GlcNAc alpha 1-->4GlcA alpha 1-->2(GlcNAc alpha 1-->4)GlcA alpha 1-->2(GlcNac alpha 1-->4)GlcA alpha 1- >2Gal, ChN<--P--> 6Man beta 1-->4GlcA alpha 1-->2Gal, and Man beta 1-->2(ChN<--P- >6)Man beta 1-->4GlcA alpha 1-->2Gal linked together with the other units reported previously [Jikibara et al. (1992) J. Biochem. 111, 236-243] through beta 1-->6galactofuranoside linkages in the acidic polysaccharide chain. PMID- 1429524 TI - High-yield production of recombinant endothelin-1. AB - A fusion protein (pETB-42P), which encodes the 42-amino acid leader peptide and the 38-amino acid peptide of human big endothelin (ET)-1, was synthesized in Escherichia coli, isolated as inclusion bodies, and purified by DEAE chromatography. Trypsin digestion of the purified pETB-42P gave big ET-1(1-37) in a yield of 70%; then pepsin digestion of the purified big ET-1(1-37) gave ET-1(1 21) in a yield of 74% (overall yield: 52%). Sequential trypsin and pepsin digestions of the purified fusion protein in the same reaction vessel also allowed recovery of ET-1 in a yield of 60%. One milligram of ET-1 or 2.0 mg of big ET-1(1-37) was obtained from 1.8 liters of culture broth. Recombinant ET-1 thus obtained was identical to authentic ET-1 in terms of amino acid sequence and vasoconstrictor potency, and recombinant big ET-1(1-37) had almost the same in vitro and in vivo biological activities as big ET-1(1-38). PMID- 1429525 TI - The primary structure of the Cytisus scoparius seed lectin and a carbohydrate binding peptide. AB - The complete amino acid sequence of 2-acetamido-2-deoxy-D-galactose-binding Cytisus scoparius seed lectin II (CSII) was determined using a protein sequencer. After digestion of CSII with endoproteinase Lys-C or Asp-N, the resulting peptides were purified by reversed-phase high performance liquid chromatography (HPLC) and then subjected to sequence analysis. Comparison of the complete amino acid sequence of CSII with the sequences of other leguminous seed lectins revealed regions of extensive homology. The amino acid residues of concanavalin A (Con A) involved in the metal binding site are highly conserved among those of CSII. A carbohydrate-binding peptide of CSII was obtained from the endoproteinase Asp-N digest of CSII by affinity chromatography on a column of GalNAc-Gel. This peptide was retained on the GalNAc-Gel column and was presumed to have affinity for the column. The amino acid sequence of the retarded peptide was determined using a protein sequencer. The retarded peptide was found to correspond to the putative metal-binding region of Con A. These results strongly suggest that this peptide represents the carbohydrate-binding and metal ion-binding sites of CSII. PMID- 1429526 TI - Induction and characterization of two types of ATPase on rat liver peroxisomes. AB - Clofibrate increased oligomycin-resistant ATPase activity in peroxisomes more than 17-fold (5.15 +/- 0.71 milliunits/mg protein) in rat liver. The activity was dependent on divalent cations (Mg2+ > Ca2+) with an optimum pH of 7.5. This activity was partially inhibited by N-ethylmaleimide (NEM), 4,4' dithiocyanatostilbene-2,2'-disulfonic acid (DIDS), silicotungstic acid (STA), and high concentrations of N,N'-dicyclohexylcarbodiimide (DCCD). Proteinase K digestion of intact peroxisomes severely reduced the NEM-sensitive activity, but little affected the NEM-resistant activity. NEM-sensitive and -resistant ATPases showed Km values for ATP of 780 and 73 microM, respectively. The NEM-sensitive activity was inhibited completely by DIDS, 7-chloro-4- nitrobenzo-2-oxa-1,3 diazole (NBD-Cl), tributyltin chloride (TBT), and quercetin, and partially by DCCD and STA, whereas the NEM-resistant activity was totally insensitive to these chemicals except for STA. These activities had unique requirements for divalent cations, anions, and substrates, respectively. They were partially separated by gel filtration chromatography and had molecular masses of 520 kDa (NEM-sensitive enzyme) and 450 kDa (NEM-resistant enzyme), respectively. PMID- 1429527 TI - Distribution of 1,5-anhydro-D-glucitol in normal, diabetic, and perfused rat bodies. AB - The concentration of 1,5-anhydro-D-glucitol (AG) was determined in various organs and tissues of normal rats and rats rendered diabetic with streptozocin, using an AG-assay method in which AG was extracted after acid hydrolysis of the whole tissues. The organs and tissues examined included skin, muscle, liver, and kidney. The plasma of control rats contained 3-12 micrograms/ml of AG. In these rats, all the organs examined also contained AG at concentrations not much lower than that in the corresponding plasma, except for adipose tissues and testis, which have relatively small water spaces; the latter two contained AG at relatively low concentrations. In contrast, both the plasma and various organs of the diabetic rats contained only trace amounts of AG. The whole body perfusion of control rats depleted AG from most of the organs, the exception being spleen, the circulation system of which is known to have a structure that is difficult wash by means of perfusion. These observations indicated that AG readily diffused into the inter- and intra-cellular water spaces from the circulation. Accordingly, the plasma membranes of the cells in these organs were suggested to be permeable to AG. PMID- 1429528 TI - Biosynthesis of the blood group P antigen-like GalNAc beta 1-->3Gal beta 1- >4GlcNAc/Glc structure: a novel N-acetylgalactosaminyltransferase in human blood plasma. AB - Human blood group O plasma was found to contain an N acetylgalactosaminyltransferase which catalyzes the transfer of N acetylgalactosamine from UDP-GalNAc to Gal beta 1-->4Glc, Gal beta 1-->4GlcNAc, asialo-alpha 1-acid glycoprotein, and Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1- >4Glc-ceramide, but not to Gal beta 1-->3GlcNAc. The enzyme required Mn2+ for its activity and showed a pH optimum at 7.0. The reaction products were readily hydrolyzed by beta-N-acetylhexosaminidase and released N-acetylgalactosamine. Apparent Km values for UDP-GalNAc, Mn2+, lactose, N-acetyllactosamine, and terminal N-acetyllactosaminyl residues of asialo-alpha 1-acid glycoprotein were 0.64, 0.28, 69, 20, and 1.5 mM, respectively. Studies on acceptor substrate competition indicated that all the acceptor substrates mentioned above compete for one enzyme, whereas the enzyme can be distinguished from an NeuAc alpha 2- >3Gal beta-1,4-N-acetylgalactosaminyltransferase, which also occurs in human plasma. The methylation study of the product formed by the transfer of N acetylgalactosamine to lactose revealed that N-acetylgalactosamine had been transferred to the carbon-3 position of the beta-galactosyl residue. Although the GalNAc beta 1-->3Gal structure is known to have the blood group P antigen activity, human plasma showed no detectable activity of Gal alpha 1-->4Gal beta 1,3-N-acetylgalactosaminyltransferase, which is involved in the synthesis of the major P antigen-active glycolipid, GalNAc beta 1-->3Gal alpha 1-->4Gal beta 1- >4Glc-ceramide. Hence, the GalNAc beta 1-->3Gal beta 1-->4GlcNAc/Glc structure is synthesized by the novel Gal beta 1-->4GlcNAc/Glc beta-1,3-N acetylgalactosaminyltransferase. PMID- 1429529 TI - Characterization of endothelin receptors ETA and ETB expressed in COS cells. AB - The cloned cDNA genes for endothelin receptors ETA and ETB were expressed in COS cells, and the binding characteristics of the two receptors with three isopeptide ligands (ET-1, ET-2, and ET-3) were examined in detail. The results indicated that the stability of receptor-ET-1 complexes formed with ETA and ETB were significantly different from each other, while their affinities to ET-1 were similar. The preformed ETA-ET-1 complex readily dissociated upon SDS-PAGE, as did many of the other receptors so far studied, while the ETB-ET-1 complex survived SDS-PAGE when it was run at low temperature (approximately 4 degrees C). Clear differences in stability were also shown in comparative studies of acid treatment of the two types of complexes. Only the ETB-ET-1 complex was resistant to acid treatment (0.2 M acetic acid, 0.5 M NaCl), and its 50 kDa monomeric receptor ligand complex remained intact. The ETB-ET-1 complex (50 kDa) formed at 4 degrees C on the surface of COS cells, however, was susceptible to limited proteolysis at 37 degrees C that reduced the molecular size of the complex to a distinct 35 kDa. No such size reduction was observed with the preformed ETA-ET-1 complex. The overall structure of two endothelin receptors, as deduced from the sequence of cloned cDNAs, is similar in many respects. However, the present findings demonstrate distinct differences in the biochemical nature of the two receptors, which suggest their distinct biological functions. PMID- 1429530 TI - Actin-actin contact: inhibition of actin-polymerization by subdomain 4 peptide fragments. AB - F-Actin was digested with alpha-chymotrypsin in 6 M urea, and two peptide fragments from subdomain 4 of actin molecule [Kabsch, W., Mannherz, H.G., Suck, D., Pai, E.F., & Holmes K.C. (1990) Nature 347, 37-44] were purified by reverse phase HPLC and Sephadex G-50 gel filtration. The peptide fragments were identified as segments from Arg-177 to Tyr-198 (2.6-kDa peptide) and from Ser-199 to Tyr-279 (9.1-kDa peptide). Their effects on actin polymerization induced by 50 or 100 mM KCl were studied by measuring the increase in viscosity by the falling ball method. The 2.6-kDa peptide decreased the rate of actin polymerization and increased the critical concentration for the polymerization. Based on the atomic model of the actin filament [Holmes, K.C., Popp, D., Gebhard, W., & Kabsch, W. (1990) Nature 347, 44-49], the peptide is presumed to bind to the barbed end of the actin filament and inhibit the polymerization. By assuming that the peptide affected the rate of association of the actin monomer to the end of the actin filament, well-fitting curves for the polymerization kinetics were calculated. Computer-assisted results indicated that the dissociation constant of the 2.6-kDa peptide for F-actin is 200 to 260 microM. In contrast, the 9.1-kDa peptide only slightly inhibited actin polymerization. These results suggest that the actin actin interface in the region between Arg-177 and Tyr-198 has a stronger interaction than those between Ser-199 and Tyr-279. The amino acid sequence L-T-D Y-L present in the 2.6-kDa segment is homologous to a common sequence in the F actin capping domain of various actin-binding proteins. PMID- 1429531 TI - Possible involvement of cathepsin L in processing of rat liver hexokinase to eliminate mitochondria-binding ability. AB - A previously found proteinase possibly involved in the modification of hexokinase to eliminate the mitochondria-binding ability without appreciable change in the catalytic activity (called hexokinase-processing enzyme hereafter), was purified by sequential chromatographies from rat liver and its properties were examined. The hexokinase-processing enzyme had carbohydrate moieties as evidenced by adsorption on immobilized concanavalin A, and had a molecular weight of about 23,000 as estimated by SDS-PAGE and gel filtration chromatography. Benzyloxycarbonyl-phenylalanyl-L-arginine-4-methylcoumaryl-7-amide (Z-Phe-Arg MCA)-hydrolyzing activity was co-purified with this processing activity throughout the purification, while the hydrolyzing activity for benzyloxycarbonyl L-arginyl-L-arginine-4-methylcoumaryl-7-amide (Z-Arg-Arg-MCA) was not. The processing activity, as well as Z-Phe-Arg-MCA hydrolyzing activity, was highly sensitive to cysteine proteinase inhibition, for example, by leupeptin and N-[N-3 (trans-carboxirane-2-carbonyl)-L-leucyl]agmatine (E-64). Furthermore, the enzyme preparation reacted with an antibody against cathepsin L purified from rat kidney. These results indicated that cathepsin L may be involved in the above mentioned processing of hexokinase. PMID- 1429532 TI - 1H-NMR comparative study of the active site in shark (Galeorhinus japonicus), horse, and sperm whale deoxy myoglobins. AB - 1H-NMR spectra of deoxy myoglobins (Mbs) from shark (Galeorhinus japonicus), horse, and sperm whale have been studied to gain insights into their active site structure. It has been demonstrated for the first time that nuclear Overhauser effect (NOE) can be observed between heme peripheral side-chain proton resonances of these paramagnetic complexes. Val-E11 methyl and His-F8 C delta H proton resonances of these Mbs were also assigned from the characteristic shift and line width. The hyperfine shift of the former resonance was used to calculate the magnetic anisotropy of the protein. The shift analysis of the latter resonance, together with the previously assigned His-F8 N delta H proton resonance, revealed that the strain on the Fe-N epsilon bond is in the order horse Mb approximately whale Mb < shark Mb and that the hydrogen bond strength of the His-F8 N delta H proton to the main-chain carbonyl oxygen in the preceding turn of the F helix is in the order shark Mb < horse Mb < whale Mb. Weaker Feporphyrin interaction in shark Mb was manifested in a smaller shift of the heme methyl proton resonance and appears to result from distortion of the coordination geometry in this Mb. Larger strain on the Fe-N epsilon bond in shark Mb should be to some extent attributed to its lowered O2 affinity (P50 = 1.1 mmHg at 20 degrees C), compared to whale and horse Mbs. PMID- 1429533 TI - Study on the interaction between soybean beta-amylase and substrate by the stopped-flow method. AB - The hydrolysis of substrates (maltoheptaose, maltopentaose, and maltotetraose) catalyzed by soybean beta-amylase [EC 3.2.1.2] at pH 5.4 and 25 degrees C was followed by monitoring small changes in the quenching of fluorescence due to tryptophan residues by the stopped-flow method. By analysis of whole time course, the dissociation constants, KdS, of enzyme-substrate and enzyme-product complexes were reasonably evaluated; and the difference in fluorescence intensities per mol between the enzyme-complex (ES or EP) and the free enzyme, delta F, was determined. The molecular activity, k0, was also determined by a new method of half time analysis. The KdS and k0 values are in good agreement with our kinetic data reported previously. The delta Fs of substrates were of smaller magnitude than those of products (G2 and G3), which means that the higher the binding affinity of the ligand is, the smaller the delta F value is. This indicates that at least two tryptophan residues must be located in the active site if the enzyme is rigid, or that if there is only one, the active site must undergo a structural change caused by the binding of ligand. PMID- 1429534 TI - F-type ATPases. Introduction. PMID- 1429535 TI - Quaternary structure of ATP synthases: symmetry and asymmetry in the F1 moiety. AB - It has been proposed that during ATP synthesis/hydrolysis F1 ATPases experience a complex pattern of nucleotide binding and release during the catalytic cycle (binding change mechanism). This type of mechanism has implications that can be correlated with the structure of the enzyme. F1-ATPases (stoichiometry alpha 3 beta 3 gamma delta epsilon) are essentially a symmetrical trimer of pairs of the major subunits (alpha and beta); the minor subunits (gamma, delta and epsilon) are in single copies and interact with the trimer in an asymmetrical fashion. The asymmetry introduced by the minor subunits has important structural and functional consequences: (1) it introduces differences between the potentially equivalent binding and catalytic sites in the major subunits, (2) it restricts the ways in which a binding change mechanism can occur, and (3) it governs the way in which the F1 interacts with the (asymmetrical) F0 sector. PMID- 1429536 TI - Structure of the Escherichia coli ATP synthase and role of the gamma and epsilon subunits in coupling catalytic site and proton channeling functions. AB - The structure of the Escherichia coli ATP synthase has been studied by electron microscopy and a model developed in which the alpha and beta subunits of the F1 part are arranged hexagonally (in top view) alternating with one another and surrounding a central cavity of around 35 A at its widest point. The alpha and beta subunits are interdigitated in side view for around 60 A of the 90 A length of the molecule. The F1 narrows and has three-fold symmetry at the end furthest from the F0 part. The F1 is linked to F0 by a stalk approximately 45 A long and 25-30 A in diameter. The F0 part is mostly buried in the lipid bilayer. The gamma subunit provides a domain that extends into the central cavity of the F1 part. The gamma and epsilon subunits are in a different conformation when ATP + Mg2+ are present in catalytic sites than when ATP + EDTA are present. This is consistent with these two small subunits switching conformations as a function of whether or not phosphate is bound to the enzyme at the position of the gamma phosphate of ATP. We suggest that this switching is the key to the coupling of catalytic site events with proton translocation in the F0 part of the complex. PMID- 1429537 TI - The alpha beta complexes of ATP synthase: the alpha 3 beta 3 oligomer and alpha 1 beta 1 protomer. AB - The basic structures of the catalytic portion (F1, alpha 3 beta 3 gamma delta epsilon) of ATP synthase are the alpha 3 beta 3 hexamer (oligomer with cooperativity) and alpha 1 beta 1 heterodimer (protomer). These were reconstituted from the alpha and beta subunits of thermophilic F1 (TF1), and the alpha 3 beta 3 hexamer was crystallized. On electrophoresis, both the dimer and hexamer showed bands with ATPase activity. Using the dimer and hexamer, we studied the nucleotide-dependent rapid molecular dynamics. The formation of the hexamer required neither nucleotide nor Mg. The hexamer was dissociated into the dimer in the presence of MgADP, while the dimer was associated into the hexamer in the presence of MgATP. The hexamer, like mitochondrial F1 and TF1, showed two kinds of ATPase activity: one was cooperative and was inhibited by only one BzADP per hexamer, and the other was inhibited by three BzADP per hexamer. PMID- 1429538 TI - Identification of subunits required for the catalytic activity of the F1-ATPase. AB - F1 (alpha beta) complexes containing equimolar ratios of the alpha and beta subunits have been shown to function as active ATPases, whereas individually isolated alpha and beta subunits show no real ATPase activity. These results indicate that the single-copy subunits are not required for F1-ATPase activity. The minimal F1 (alpha beta)-core complexes exhibit, however, lower rates and some different properties from those of their parent whole F1 or alpha 3 beta 3 gamma complexes. It is therefore concluded that for obtaining a full spectrum of the characteristic functional properties of an F1-ATPase the presence of the F1-gamma subunit is also required. The implications of these findings on the subunit location of both catalytic and noncatalytic nucleotide binding sites is discussed. PMID- 1429539 TI - A model for the catalytic site of F1-ATPase based on analogies to nucleotide binding domains of known structure. AB - An updated topological model is constructed for the catalytic nucleotide-binding site of the F1-ATPase. The model is based on analogies to the known structures of the MgATP site on adenylate kinase and the guanine nucleotide sites on elongation factor Tu (Ef-Tu) and the ras p21 protein. Recent studies of these known nucleotide-binding domains have revealed several common functional features and similar alignment of nucleotide in their binding folds, and these are used as a framework for evaluating results of affinity labeling and mutagenesis studies of the beta subunit of F1. Several potentially important residues on beta are noted that have not yet been studied by mutagenesis or affinity labeling. PMID- 1429540 TI - A glycine-rich sequence in the catalytic site of F-type ATPase. AB - Affinity labeling and genetic studies on the glycine-rich sequence of the beta subunit of E. coli F-type ATPase are discussed. A model of the structure of the enzyme near the gamma phosphate moiety is proposed. PMID- 1429541 TI - Functional sites in F1-ATPases: location and interactions. AB - This review focuses on the location and interaction of three functional sites in F1-ATPases. These are catalytic sites which are located in beta subunits, noncatalytic nucleotide-binding sites which are located at interfaces of alpha and beta subunits and modulate the hydrolytic activity of the enzyme, and a site that binds inhibitory amphipathic cations which is at an interface of alpha and beta subunits. The latter site may participate in transmission of conformational signals between catalytic sites in F1 and the proton-conducting apparatus of F0 in the intact ATP synthases. PMID- 1429542 TI - Catalytic sites of Escherichia coli F1-ATPase. AB - The catalytic site of Escherichia coli F1-ATPase is reviewed in terms of structure and function. Structural prediction, biochemical analyses, and mutagenesis experiments suggest that the catalytic site is formed primarily by residues 137-335 of beta-subunit. Subdomains of the site involved in phosphate bond cleavage/synthesis and adenine-ring binding are discussed. Ambiguities inherent in steady-state catalytic measurements due to catalytic site cooperativity are discussed, and the advantages of pre-steady-state ("unisite") techniques are emphasized. The emergence of a single high-affinity catalytic site occurs as a result of F1-oligomer assembly. Measurements of unisite catalysis rate and equilibrium constants, and their modulation by varied pH, dimethylsulfoxide, and mutations, are described and conclusions regarding the nature of the high-affinity catalytic site and mechanism of catalysis are presented. PMID- 1429543 TI - Kinetic studies of ATP synthase: the case for the positional change mechanism. AB - The mitochondrial ATP synthases shares many structural and kinetic properties with bacterial and chloroplast ATP synthases. These enzymes transduce the energy contained in the membrane's electrochemical proton gradients into the energy required for synthesis of high-energy phosphate bonds. The unusual three-fold symmetry of the hydrophilic domain, F1, of all these synthases is striking. Each F1 has three identical beta subunits and three identical alpha subunits as well as three additional subunits present as single copies. The catalytic site for synthesis is undoubtedly contained in the beta subunit or an alpha, beta interface, and thus each enzyme appears to contain three identical catalytic sites. This review summarizes recent isotopic and kinetic evidence in favour of the concept, originally proposed by Boyer and coworkers, that energy from the proton gradient is exerted not directly for the reaction at the catalytic site, but rather to release product from a single catalytic site. A modification of this binding change hypotheses is favored by recent data which suggest that the binding change is due to a positional change in all three beta subunits relative to the remaining subunits of F1 and F0 and that the vector of rotation is influenced by energy. The positional change, or rotation, appears to be the slow step in the process of catalysis and it is accelerated in all F1F0 ATPases studied by substrate binding and by the proton gradient. However, in the mammalian mitochondrial enzyme, other types of allosteric rate regulation not yet fully elucidated seem important as well. PMID- 1429544 TI - Interaction of beef-heart mitochondrial F1-ATPase with immobilized ATP in the presence of dimethylsulfoxide. AB - Dimethylsulfoxide [Me2SO, 30% (v/v)] promotes the formation of ATP from ADP and phosphate catalyzed by soluble mitochondrial F1-ATPase. The effects of this solvent on the interaction of beef-heart mitochondrial F1 with the immobilized ATP of Agarose-hexane-ATP were studied. In the presence of Me2SO, F1 bound less readily to the immobilized ATP, but once bound was more difficult to elute with exogenous ATP. This suggests that not only was the binding affinity for adenine nucleotide at the first binding site affected but that adenine nucleotide binding affinity at the second and/or third sites, which interact cooperatively with the first site to release bound nucleotide, was also affected. A reduction in the binding of [3H]ADP to these sites was shown. A change in the conformation of F1 in 30% (v/v) Me2SO was demonstrated by crosslinking and by the increased resistance of the enzyme to cold denaturation. PMID- 1429545 TI - Peter Mitchell, 1920-1992. PMID- 1429546 TI - Efraim Racker, 1913-1991. PMID- 1429547 TI - Mordhay Avron, 1931-1991. PMID- 1429548 TI - Transcriptional regulation of heat shock genes. A paradigm for inducible genomic responses. AB - The heat shock response offers an ideal paradigm to understand how the cell recognizes and responds to acute and chronic exposures to environmental and physiological stress. Of the numerous inducible genomic responses, the heat shock response has contributed fascinating insights into the molecular and cellular mechanisms of adaptation, ranging from the regulation of heat shock gene expression to the function of stress proteins. The recent cloning of multiple heat shock transcription factor (HSF) genes in higher eukaryotes and studies on the biochemical and cellular properties of HSFs have revealed several novel features of the transcriptional response. PMID- 1429549 TI - The Wilms' tumor gene product, WT1, represses transcription of the platelet derived growth factor A-chain gene. AB - The Wilms' tumor locus on chromosome 11p13 contains a tumor suppressor gene, wt1, which encodes a DNA binding protein (WT1) with four zinc fingers and a glutamine proline-rich N terminus and which functions as a repressor of transcription. The platelet-derived growth factor (PDGF) A-chain gene encodes a potent growth factor, which is expressed in high levels in a number of tumor cell lines. We initiated a search for WT1 target genes and now report that WT1 strikingly represses transcription of the PDGF A-chain gene in transient transfection assays and that the WT1 protein interacts directly with a highly G+C-rich region of the PDGF A-chain promoter in gel mobility shift assays. The results suggest that WT1 may function to repress expression of the PDGF A-chain gene and that loss of this or related repressor activities may contribute to the abnormal growth of Wilms' tumors. PMID- 1429550 TI - Purification of 2,3-oxidosqualene cyclase from rat liver. AB - A rapid and simple purification of milligram amounts of 2,3-oxidosqualene cyclase, an integral membrane enzyme that catalyzes the cyclization of squalene epoxide to lanosterol, is reported. Several nonionic detergents (Triton X-100, Tween 80, Emulphogene, and lauryl maltoside) were evaluated for solubilization of oxidosqualene cyclase from rat liver microsomes. At a detergent concentration of 5 mg/ml, lauryl maltoside was approximately 10 times more effective than Emulphogene in the solubilization of oxidosqualene cyclase; Triton X-100 and Tween 80 were less effective than Emulphogene as judged by the relative specific activities of the solubilized enzyme. Treatment of microsomes with lauryl maltoside resulted in a selective solubilization of the cyclase with concomitant activation of the enzyme. The solubilized enzyme was purified to homogeneity by fast protein liquid chromatography. The purified enzyme consists of a single subunit that has an apparent molecular weight of 65,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme obeys saturation kinetics and the apparent Km of (2,3)-oxidosqualene is 15 microM; the apparent kcat/Km is 200 M-1.min-1. An improved assay of the enzyme that utilizes high performance liquid chromatography methods is also described. PMID- 1429551 TI - Electrogenic uptake of gamma-aminobutyric acid by a cloned transporter expressed in Xenopus oocytes. AB - GAT-1, a gamma-aminobutyric acid (GABA) transporter cloned from rat brain, was expressed in Xenopus oocytes. Voltage-clamp measurements showed concentration dependent, inward currents in response to GABA (K0.5 4.7 microM). The transport current required extracellular sodium and chloride ions; the Hill coefficient for chloride was 0.7, and that for sodium was 1.7. Correlation of current and [3H]GABA uptake measurements indicate that flux of one positive charge occurs per molecule of GABA transported. Membrane hyperpolarization from -40 to -100 mV increased the transport current approximately 3-fold. The results indicate that the transport of one molecule of GABA involves the co-transport of two sodium ions and one chloride ion. PMID- 1429552 TI - Distal pocket residues affect picosecond ligand recombination in myoglobin. An experimental and molecular dynamics study of position 29 mutants. AB - Time courses for intramolecular NO and O2 recombination to native and three position 29 mutants of sperm whale myoglobins were measured after laser photolysis on picosecond and nanosecond time scales. The rates for the first phase of NO recombination were 1.8, 2.5, 29, and > or = 100 ns-1 for Ala29, Val29, Leu29 (native), and Phe29 myoglobin, respectively, at room temperature. This order is not correlated with the overall association rate constants for NO binding which were all in the range 20-50 x 10(6) M-1 s-1 and is the opposite of that observed for the rate constants for the overall thermal dissociation of NO which were 5.0, 2.8, 0.98, and 0.21 x 10(-4) s-1 for Ala29, Val29, Leu29 (native), and Phe29 myoglobin, respectively, at 20 degrees C. This inverse correlation suggests that photo- and thermally dissociated ligand molecules experience similar kinetic and equilibrium barriers to rebinding. The larger side chains of Leu29 and Phe29 inhibit rapid movement of the ligand away from the iron atom facilitating geminate recombination. The smaller side chains of Val29 and Ala29 increase the space available to the ligand, decreasing the rate of geminate recombination and enhancing complete dissociation. Diffusion of NO in the distal pocket of myoglobin was simulated using a variant of the molecular dynamics program CHARMM that includes the locally enhanced sampling protocol (Elber, R., and Karplus, M. (1991) J. Am. Chem. Soc. 112, 9161-9175; Roitberg, A., and Elber, R. (1991) J. Chem. Phys. 95, 9277-9287) and the x-ray structures of Carver et al. (Carver, T. E., Brantley, R. E., Jr., Singleton, E. W., Arduini, R. M., Quillin, M. L., Phillips, G. N., Jr., and Olson, J. S. (1992) J. Biol. Chem. 267, 14443 14450). Both accelerated (5,000 K) and room temperature ligands were used, and comparisons were made between simulations with a complete hydration shell surrounding the protein and those with only eight water molecules near the distal histidine. Photodissociated ligands initially move away from the heme plane, past Leu29, and toward Leu32, Phe33, Ile107, and Ile111. These theoretical results confirm that a complete description of picosecond ligand recombination must include the dynamics of ligand movement in the distal portion of the heme pocket. PMID- 1429553 TI - Down-regulation of interleukin 6 receptors of mouse myelomonocytic leukemic cells by leukemia inhibitory factor. AB - We examined the effect of leukemia inhibitory factor (LIF) on the expression of interleukin 6 receptors (IL-6R) on mouse myelomonocytic leukemic M1 cells. Binding studies using 125I-labeled human and murine IL-6 revealed that LIF caused a decrease in IL-6 binding to M1 cells. The decrease became evident within 1 h, and the maximum decrease was observed at 3-6 h. Scatchard plot analysis revealed that M1 cells had a single class of high affinity receptors for IL-6 and that LIF induced decrease in IL-6 binding was due to a decrease in the number of IL-6R on the cell surface and not to changes in their affinity. The affinity of IL-6R on M1 cells to human IL-6 (Kd = 2.25 nM) was about 10-fold lower than that to murine IL-6 (Kd = 200 pM). The amount of IL-6 secreted into culture media by M1 cells that were treated with LIF for up to 12 h was not enough to cause receptor down regulation. Northern blot analysis demonstrated that IL-6R mRNA was down regulated by LIF treatment, and similar regulation was also observed when the cells were treated with IL-6. The time course of the IL-6R mRNA level was similar to that of IL-6R expression on the cell surface, suggesting that the main mechanism responsible for the loss of high affinity IL-6R was the regulation of IL-6R mRNA. Although the half-life of IL-6R on the cell surface was about 30 min, the addition of LIF reduced it to 16 min, suggesting the existence of an additional mechanism responsible for the loss of high affinity IL-6R on the cell surface. PMID- 1429554 TI - The stereospecific interaction between chlorophylls and chlorophyllase. Possible implication for chlorophyll biosynthesis and degradation. AB - Chlorophyllase-catalyzed hydrolysis and esterification of chlorophylls, bacteriochlorophylls, and their free acids, respectively, depend on the configuration around the C-13(2) atom of the corresponding substrate. The data suggest that the enzyme interacts preferentially with compounds having the isocyclic carbomethoxy and the C-17 propionic residues facing opposite sides of the porphyrin macrocycle. The relevance of this observation to chlorophyll biosynthesis and degradation in vivo is briefly discussed. PMID- 1429555 TI - Reversible membrane association of neutrophil 5-lipoxygenase is accompanied by retention of activity and a change in substrate specificity. AB - Ionophore activation of the human polymorphonuclear neutrophil results in eicosanoid synthesis and the accumulation of inactive 5-lipoxygenase in a membrane compartment. We report here that inhibition of self-inactivation of 5 lipoxygenase in ionophore-treated neutrophils with the reversible inhibitor zileuton, results in the accumulation of active 5-lipoxygenase in the membrane fraction. In zileuton plus ionophore-treated cells, 77% of the specific activity of the cytosolic enzyme from resting cells was diverted to the membrane fraction compared to 22% of the activity translocated when ionophore alone was used to activate the neutrophils. Accumulation of active membrane-associated 5 lipoxygenase was inhibited and reversed by the 5-lipoxygenase translocation inhibitor MK-886. The membrane-associated 5-lipoxygenase was two times more efficient in the production of leukotriene A4 from arachidonate-derived 5 hydroperoxyeicosatetraenoic acid than the cytosolic enzyme. Unlike the cytosolic enzyme, membrane-associated 5-lipoxygenase could metabolize 12(S)- and 15(S) hydroxyeicosatetraenoic acid to 5(S),12(S)- and 5(S),15(S) dihydroxyeicosatetraenoic acid, respectively. The ability to metabolize hydroxy fatty acids was dependent upon 5-lipoxygenase-activating protein association, but was lost if 5-lipoxygenase was eluted from the membrane by MK-886. These studies reveal for the first time that significant quantities of active 5-lipoxygenase can be detected in the membrane fraction of activated neutrophils and show that membrane association can alter the substrate specificity of 5-lipoxygenase which is further evidence for the role of the membrane-associated enzyme in the synthesis of 5-lipoxygenase metabolites. PMID- 1429556 TI - Identification of actin and HSP 70 as cyclosporin A binding proteins by photoaffinity labeling and fluorescence displacement assays. AB - A novel family of cyclosporin A (CsA) binding proteins was identified by using the biologically active, radioiodinated photoaffinity probe [D-Lys-N epsilon-(4 azido-3-[125I]iodophenyl)propionyl)]8-CsA. In addition to cyclophilin, proteins with molecular masses of 43 kDa and approximately 50-55 kDa were labeled in Jurkat extracts and bovine calf thymus. Sequence analysis of the 43-kDa protein purified from calf thymus and subsequent Western analysis of CsA affinity purified material from Jurkat extracts identified the 43-kDa component as actin. [D-Lys-N epsilon-(5-dimethylamino-1-naphthalenesulfonyl)]8-CsA, a fluorescent analogue of CsA, was prepared and used to measure the binding constants of cyclosporin derivatives to actin by means of a new fluorescence displacement assay. [D-Lys-N epsilon-(5-dimethylamino-1-naphthalenesulfonyl)]8-CsA and [N delta-t-butoxycarbonyl diaminobutyryl)]8-CsA bind to bovine actin at physiologically relevant concentrations, with dissociation constants of 60 +/- 33 and 570 +/- 380 nM, respectively. Because the ATPase fragment of heat shock cognate 70 (HSC 70) is structurally related to actin, the yeast homologue SSA1 was tested and found to be radiolabeled by the cyclosporin A photoaffinity reagent. The binding constant for [D-Lys-N epsilon-(5-dimethylamino-1 naphthalenesulfonyl)]8-CsA to SSA1 was determined and is 53 +/- 48 nM. These results indicate that actin and the 70-kDa heat shock protein family contain a structurally related domain for binding of cyclosporin A-related peptides. PMID- 1429557 TI - Parallel control of hepatic proteolysis by phenylalanine and phenylpyruvate through independent inhibitory sites at the plasma membrane. AB - Intracellular protein degradation in the rat hepatocyte is regulated by 7 amino acids of which Leu, Gln, and Tyr play major roles. Although Phe is known to inhibit proteolysis as effectively as Tyr at high concentrations, it has not been regarded as an active regulator because of its rapid hydroxylation to Tyr. We now show that proteolytic responses to Phe during liver perfusion differ strikingly from effects of the multiphasic regulators Leu, Gln, and Tyr in eliciting mirror image responses at half-normal and normal plasma concentrations. Since response curves to phenylpyruvate and Phe were identical, we considered the possibility that phenylpyruvate mediated its anomalous inhibition intracellularly. However, when phenylpyruvate was produced from phenyllactate intracellularly at a rate providing the same rate of transamination (and intracellular concentration) as that derived from the uptake of phenylpyruvate, no response was obtained. Hence, the effect of phenylpyruvate was not initiated within the cell but more likely from the plasma membrane. Comparable evidence for Phe is less direct. Recent findings indicate that recognition sites for Leu and Gln are located at the plasma membrane. Since Phe augments the concerted inhibition by Leu and Gln at 4 fold normal levels, Phe is probably recognized in close proximity to them. However, the failure of phenylpyruvate to substitute for Phe in this interaction suggests that proteolytic inhibition by phenylpyruvate and Phe is mediated through similar, although independent, plasma membrane sites. PMID- 1429558 TI - Control of hepatic proteolysis by leucine and isovaleryl-L-carnitine through a common locus. Evidence for a possible mechanism of recognition at the plasma membrane. AB - Deprivation-induced proteolysis in the perfused rat liver is controlled through the multiphasic action of 7 regulatory amino acids of which L-leucine plays the dominant role. Recently, isovaleryl-L-carnitine (IVC) was shown to mimic the leucine's effects, suggesting that the two molecules share structural features that are recognized at a common site(s). In this study we find that each evokes identical responses consisting of inhibitory effects at 0.08 and 0.8 mM, separated by a sharp zonal loss of inhibition at 0.15 mM. As monitored by density shifts of beta-hexosaminidase in colloidal silica gradients, macroautophagy is suppressed by both. Responses to Leu and IVC at 0.08 and 0.15 mM are stereospecific and require a reactive group at the alpha-carbon (or equivalent) and a high degree of branched chain specificity. In addition, 0.5 mM Ala coregulates with IVC and Leu by decreasing the zonal loss at 0.15 mM. The fact that the multiphasic responses can be duplicated with equimolar mixtures of Leu + IVC indicates that both react at the same site(s). IVC is readily taken up by a saturable process, but owing to its rapid hydrolysis in the cell, the ratio of internal to external IVC remains low over a 4-fold concentration range. These findings, together with a kinetic analysis of concerted responses to regulatory amino acids, suggest that the recognition sites are at a position in the cell, possibly at the plasma membrane, to react reversibly with plasma amino acids. PMID- 1429559 TI - The lymphoma transmembrane glycoprotein GP85 (CD44) is a novel guanine nucleotide binding protein which regulates GP85 (CD44)-ankyrin interaction. AB - In this study, we have used photoaffinity labeling by [32P]azido-GTP as well as [32P]ADP-ribosylation by pertussis toxin (PT) and cholera toxin (CT) to identify GTP-binding proteins associated with mouse T-lymphoma plasma membranes. Our results indicate that GP85 (CD44) can be photoaffinity labeled by [32P] azido-GTP and [32P]ADP-ribosylated by both PT and CT. Using purified GP85 (CD44) obtained by Triton X-100 extraction, wheat germ agglutinin-Sepharose, and anti-GP85 (CD44) antibody affinity chromatographies, we have further characterized GP85 (CD44) as a GTP-binding protein. GP85 (CD44) is found to bind guanosine 5'-3-O (thio)triphosphate (GTP gamma S) in a time- and dose-dependent manner with a dissociation constant of 0.83 nM. Importantly, GP85 (CD44) appears to display a GTPase activity which hydrolyzes [gamma-32P]GTP at a rate of 0.011 mol of Pi released/mol of GP85 (CD44)/min. This GTPase activity can be readily inhibited by PT- or CT-mediated ribosylation of GP85 (CD44). Most interestingly, GTP binding significantly enhances the interaction of purified GP85 (CD44) with ankyrin, whereas ADP-ribosylation of GP85 (CD44) by PT or CT inhibits the GTP-induced increase in ankyrin binding to GP85 (CD44). In addition to GP85 (CD44) being the first reported transmembrane GTP-binding protein, these results suggest that GTP plays an important role in promoting the interaction between GP85 (CD44) and its underlying membrane cytoskeleton through ankyrin. PMID- 1429560 TI - L-threonine transport in pig jejunal brush border membrane vesicles. Functional characterization of the unique system B in the intestinal epithelium. AB - Uptake and inhibitory kinetics of [3H]L-threonine were evaluated in preparations of pig jejunal brush border membrane vesicles. Uptake of [3H]L-threonine under O trans, Na+ gradient, and O-trans, Na(+)-free conditions was best described by high affinity transport (Km < 0.01 mM) plus a nonsaturable component. The maximal velocity of transport was 3-fold greater under Na+ gradient conditions. 100 mM concentrations of all of the dipolar amino acids and 2-aminobicyclo[2.2.1]heptane 2-carboxylic acid caused complete inhibition of [3H]L-threonine transport under Na+ gradient and Na(+)-free conditions. Imino acids, anionic amino acids, cationic amino acids, and methylamino-isobutyric acid caused significant partial inhibition of L-threonine uptake. Inhibitor concentration profiles for proline and lysine were consistent with low affinity competitive inhibition. The Ki values of alanine and phenylalanine approximated 0.2 and 0.5 mM, respectively, under both Na+ gradient and Na(+)-free conditions. These data indicate that the transport system available for L-threonine in the intestinal brush border membrane (system B) is functionally distinct from other amino acid transport systems. Comparison of kinetics parameters in the presence and absence of a Na+ gradient suggests that both partially and fully loaded forms of the carrier can function to translocate substrate and that Na+ serves to accelerate L-threonine transport by a mechanism that does not involve enhanced substrate binding. PMID- 1429561 TI - Lactose transport system of Streptococcus thermophilus. Functional reconstitution of the protein and characterization of the kinetic mechanism of transport. AB - The kinetic mechanism of the lactose transport system of Streptococcus thermophilus was studied in membrane vesicles fused with cytochrome c oxidase containing liposomes and in proteoliposomes in which cytochrome c oxidase was coreconstituted with the lactose transport protein. Selective manipulation of the components of the proton (and sodium) motive force indicated that both a membrane potential and a pH gradient could drive transport. The galactoside/proton stoichiometry was close to unity. Experiments which discriminate between the effects of internal pH and delta pH as driving force on galactoside/proton symport showed that the carrier is highly activated at alkaline internal pH values, which biases the transport system kinetically toward the pH component of the proton motive force. Galactoside efflux increased with increasing pH with a pKa of about 8, whereas galactoside exchange (and counterflow) exhibited a pH optimum around 7 with pKa values of 6 and 8, respectively. Imposition of delta pH (interior alkaline) retarded the rate of efflux at any pH value tested, whereas the rate of exchange was stimulated by an imposed delta pH at pH 5.8, not affected at pH 7.0, and inhibited at pH 8.0 and 9.0. The results have been evaluated in terms of random and ordered association/dissociation of galactoside and proton on the inner surface of the membrane. Imposition of delta psi (interior negative) decreased the rate of efflux but had no effect on the rate of exchange, indicating that the unloaded transport protein carries a net negative charge and that during exchange and counterflow the carrier recycles in the protonated form. PMID- 1429563 TI - Purification and partial characterization of candidate antidiuretic hormone water channel proteins of M(r) 55,000 and 53,000 from toad urinary bladder. AB - Antidiuretic hormone (ADH) increases toad bladder granular cell apical membrane osmotic water permeability (Pf) by insertion of cytoplasmic vesicles containing water channels into the apical membrane. Termination of ADH stimulation results in endocytosis of water channel-containing membrane. In previous work, we have purified water channel-containing vesicles and demonstrated that they contain 12 major protein bands when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). On the basis of vectorial labeling studies of granular cells and purified vesicles, we have proposed previously that vesicle proteins of 55, 53, and 17 kDa are ADH water channel components. In this report, we have purified and analyzed these three proteins using a combination of SDS PAGE, peptide mapping, amino acid composition, and amino-terminal analyses. The 55- and 53-kDa proteins are distinct protein species possessing a high degree of structural similarity. Both possess a large content of cysteine. The 17-kDa protein appears to be a proteolytic fragment of the 53-kDa protein. None of these three proteins is phosphorylated or contains large amounts of covalently linked carbohydrate. ADH-elicited Pf is inhibited by the organic mercurial reagent fluorescein mercuric acetate (FMA). Exposure of water channel-containing vesicles to FMA labels selectively four vesicle proteins of 92, 55, 53, and 29 kDa while reducing vesicle Pf by 82%. The combination of FMA and 2-mercaptoethanol or exposure to another mercurial reagent, n-ethylmaleimide, does not inhibit vesicle Pf. Together, these data provide additional evidence for the role of the 55- and 53-kDa proteins as components of the ADH water channel. These candidate ADH water channel proteins are distinct from a 28-kDa candidate water channel protein (CHIP 28) isolated recently from human erythrocyte membranes and kidney proximal tubule by Agre and co-workers (Preston, G. M., Carroll, T. P., Guggino, W. B., and Agre, P. (1992) Science 256, 385-387). PMID- 1429562 TI - The regulation of the human tumor necrosis factor alpha promoter region in macrophage, T cell, and B cell lines. AB - The 1311-base pair human tumor necrosis factor (TNF) alpha promoter region was fused to the luciferase (Luc) reporter gene and studied in a transient transfection system in three TNF producing cell lines, the U937 macrophage cell line, the MLA 144 T cell line, and the 729-6 B cell line. This full length promoter construct can be induced by phorbol 13-myristate acetate (PMA) in each of these cell types. Analysis of a series of 5'-truncations showed several peaks of basal and PMA induced activity suggesting the presence of several positive and negative regulatory elements. A PMA responsive element was localized to a region between -95 and -36 bp relative to the transcription start site. Within this region, single AP-2- and AP-1-like consensus sequences were noted. These AP-2 and AP-1 sites were each modified with a double point mutation. A modest (20-50%) reduction in TNF promoter activity was observed with the AP-2 site mutation. However, mutation of the AP-1 site markedly diminished both the basal and PMA activated promoter activity. Also co-transfections of the wild-type promoter construct with an AP-1/c-jun expression vector resulted in augmented basal and PMA-induced promoter activity. PMID- 1429564 TI - 1.9-A resolution structure of fasciculin 1, an anti-acetylcholinesterase toxin from green mamba snake venom. AB - The crystal structure of fasciculin 1, a potent acetylcholinesterase inhibitor from green mamba snake venom, has been solved by the multiple isomorphous replacement method complemented with anomalous scattering and subsequently refined at 1.9-A resolution. The overall structure of fasciculin is similar to those of the short alpha-neurotoxins and cardiotoxins, with a dense core rich in disulfide bridges and three long loops disposed as the central fingers of a hand. A comparison of these three prototypic toxin types shows that fasciculin 1 has structural features that are intermediate between those of the other two molecules. Its core region, which can be defined as a continuous stretch of conserved residues, is very similar to that of erabutoxin b, whereas the orientation of its long loops resembles that of cardiotoxin VII4. This result introduces a new element in the study of phylogenetic relationships of snake toxins and suggests that, after divergency from an ancestral gene, convergent evolution may have played an important factor in the evolution of these proteins. In fasciculin 1, several arginine and lysine residues are well ordered and relatively exposed to the solvent medium and may play a role in the binding to the peripheral site of acetylcholinesterases. PMID- 1429566 TI - On the mechanisms of the formation of L-alloisoleucine and the 2-hydroxy-3 methylvaleric acid stereoisomers from L-isoleucine in maple syrup urine disease patients and in normal humans. AB - 2-Keto-3-methylvaleric acid (KMVA) has been found not to undergo spontaneous keto enol tautomerization in neutral aqueous solution, alone or in the presence of large concentrations of pyridoxamine or pyridoxamine-5-phosphate. This finding denies the commonly held suppositions that 3R-KMVA is derived spontaneously from 3S-KMVA in vivo, and that L-alloisoleucine is the product of the reamination of this 3R-KMVA. Evidence presented here suggests that racemization of the 3-carbon of L-isoleucine occurs during transamination, that L-alloisoleucine is an inherently unavoidable by-product of L-isoleucine transamination (and vice versa), and that a KMVA enol is not obligate in this racemization. The four stereoisomers of 2-hydroxy-3-methylvaleric acid have been synthesized and the mass spectra of their trimethylsilyl derivatives recorded. An achiral methylsilicone column was used to separate the diastereomeric pairs and to determine their relative ratios in plasma and urine from normal controls and two maple syrup urine disease (MSUD) patients. The urinary ratio of the two diastereomers is different from that for plasma, both in normals and in MSUD patients. The plasma ratios may provide a rapid and simple measure of residual branched chain 2-keto acid dehydrogenase activity in MSUD patients. PMID- 1429565 TI - Alternative exon usage and processing of the major histocompatibility complex encoded proteasome subunits. AB - The finding that two subunits of the proteasome, LMP2 and LMP7, are encoded in the major histocompatibility complex (MHC) has linked the proteasome which represents a major extralysosomal proteolytic system to the processing of intracellular antigens. Here we describe a second form of the human LMP7 cDNA, LMP7-E2, which has been identified during the characterization of novel genes in the MHC. The analysis of the genome organization of LMP7 revealed that LMP7-E1 and LMP7-E2 arise by alternative exon usage. Using specific antibodies against LMP2 and LMP7, we show that they are co-expressed with class I MHC molecules as well as a putative peptide transporter. The polypeptides encoded by LMP7 and LMP2 undergo proteolytic processing when incorporated into proteasomes, and the LMP7 precursor is derived mainly from LMP7-E2. Furthermore, our data suggest that LMP7 and LMP2 are mutually dependent for their incorporation into the proteasomal complex. PMID- 1429567 TI - Negative complementation in aspartate transcarbamylase. Analysis of hybrid enzyme molecules containing different arrangements of polypeptide chains from wild-type and inactive mutant catalytic subunits. AB - A comprehensive set of hybrid molecules of aspartate transcarbamylase (ATCase) from Escherichia coli has been constructed of wild-type and mutationally altered catalytic chains. The mutant enzymes that were virtually devoid of activity contained a replacement of Gly-128 in the catalytic polypeptide chains by either Asp or Arg. The kinetic properties of these hybrid enzyme-like molecules were analyzed to evaluate the basis for the unusual quaternary constraint demonstrated by an intersubunit hybrid containing one wild-type catalytic subunit, one inactive mutant subunit (containing the Gly to Asp replacement), and three wild type regulatory subunits. A similar intersubunit hybrid was constructed from the wild-type catalytic subunit and the mutant in which Gly-128 was replaced by Arg, and it too demonstrated a pronounced decrease in activity relative to that expected for a hybrid containing three active sites. Moreover, neither of these hybrid holoenzymes exhibited the cooperativity with respect to aspartate that is characteristic of wild-type ATCase. In contrast, hybrid holoenzymes containing at least one wild-type chain in each catalytic subunit showed cooperativity. Also, hybrid enzymes containing different arrangements of five, four, three, or two wild-type catalytic chains with an appropriate complement of mutant chains had specific activities proportional to the number of wild-type chains in the holoenzymes. Exceptions were observed only in hybrids in which one of the two subunits in the holoenzyme was composed completely of mutant catalytic chains. For these hybrids the negative complementation was manifested as a much lower enzyme activity than expected from the number of wild-type chains in the enzyme and the loss of cooperativity. Thus, the activity and allosteric properties of these hybrids is dependent on the arrangement of catalytic chains in the holoenzyme, in contrast to results obtained for hybrids containing native and chemically modified catalytic chains. Intrasubunit hybrid catalytic trimers containing one or two wild-type chains exhibited one-third and two-thirds the activity of the intact wild-type catalytic subunit, respectively, indicating the dominant negative effect that was seen in intersubunit hybrid holoenzymes is absent within trimers. PMID- 1429568 TI - Basic fibroblast growth factor is internalized through both receptor-mediated and heparan sulfate-mediated mechanisms. AB - Basic fibroblast growth factor (bFGF) was internalized at a rapid rate by Chinese hamster ovary (CHO) cells that do not express significant numbers of high affinity receptors for bFGF as well as CHO cells that have been transfected with cDNA encoding FGF receptor-1 or FGF receptor-2. Internalization of bFGF was completely blocked by the addition of 10 micrograms/ml heparin in the parental CHO cells but only partially inhibited in cells expressing transfected FGF receptors. Bovine aortic endothelial cells also exhibit heparin-sensitive and heparin-resistant internalization of bFGF. The internalization of bFGF through the heparin-resistant pathway in CHO cells was efficiently competed by addition of unlabeled bFGF, was proportional to the number of receptors expressed, and approached saturation, suggesting that the heparin-resistant internalization was due to high affinity receptors. Internalization of bFGF through the heparin sensitive pathway was not efficiently competed by unlabeled bFGF and did not approach saturation at concentrations of bFGF up to 50 ng/ml, properties similar to the interaction of bFGF with low affinity heparan sulfate binding sites on the cell surface. Internalization of bFGF in CHO cells not expressing FGF receptors was inhibited by heparin, heparan sulfate, and dermatan sulfate, the same glycosaminoglycans that block binding to cell-surface heparin sulfates. Internalization of bFGF in the parental CHO cells was inhibited at the same concentrations of heparin that block binding to cell-surface heparan sulfates. Finally, inhibition of the sulfation of CHO cell heparan sulfates by the addition of chlorate or digestion of CHO cell heparan sulfates with heparinase inhibited bFGF internalization in the parental CHO cells. These results demonstrate that bFGF can be internalized through a direct interaction with cell-surface heparan sulfates. Thus, there are two pathways for internalization of bFGF: high affinity receptor-mediated and heparan sulfate-mediated. PMID- 1429569 TI - Reversal of the desensitized state of pig ovarian follicular human choriogonadotropin-sensitive adenylylcyclase by guanosine 5'-O-(2 thiodiphosphate). AB - We investigated the stability of the desensitized state of the human choriogonadotropin (hCG)-sensitive adenylylcyclase of the pig ovarian follicle. A 20,000 x g membrane preparation of pig follicular membranes was incubated under conditions which resulted in the hormone-induced desensitization of the hCG responsive adenylylcyclase. The desensitized state was maintained upon subsequent incubation of the membranes with GTP, GDP, GMP, ATP, ADP, AMP, CTP, UTP, adenyl 5'-yl imidodiphosphate (AMP-P(NH)P), and adenyl (beta, gamma-methylene) diphosphonate (AMP-P(CH2)P); however, the desensitized state was reverted to a fully active state upon incubation with guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). The reversal effect of GDP beta S on hCG-responsive adenylylcyclase activity was time- and temperature-dependent, and showed a selectivity for GDP beta S over adenosine 5' O-(2-thiodiphosphate) (ADP beta S) (half-maximal effective dose of 12 microM versus 260 microM, respectively). GDP beta S had no effect on the binding affinity or apparent number of luteinizing hormone (LH)/CG receptors or on the dissociation rate of 125I-hCG from the receptor. GDP beta S promoted an hCG- and time-dependent release of guanine nucleotides from the membranes. A model is proposed which accounts for the unique characteristics of LH/CG-sensitive adenylylcyclase desensitization and subsequent reactivation by GDP beta S. PMID- 1429570 TI - Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component. AB - Differential screening of a cDNA library constructed from human umbilical vein endothelial cells exposed for 1 h to interleukin-1 beta (IL-1 beta) has led to the identification of a novel gene (PTX3) related to pentaxins (C-reactive protein and serum amyloid P component in man), a subclass of acute phase proteins. Sequencing of the full-length cDNA clone and RNase mapping revealed that the PTX3 transcript is 1861 base pairs long and has a unique transcription start site. The predicted protein sequence of 381 amino acids is highly similar to pentaxins in its COOH-terminal half where it also contains a typical 8-amino acid "pentaxin signature" sequence. The NH2-terminal half of PTX3 shows no similarity to any known protein sequence and initiates with a putative signal peptide indicating that PTX3 is secreted. The genome of PTX3 is organized into three exons. Interestingly, the region of homology between PTX3 and pentaxins corresponds to the third PTX3 exon. The PTX3 gene has been localized on human chromosome 3 band q25 by Southern blots of somatic cell hybrids and by in situ hybridization. The PTX3 mRNA is induced in endothelial, hepatic, and fibroblastic cells by IL-1 beta and tumor necrosis factor alpha but not by IL-6 and interferon gamma. PTX3 may represent a novel marker of inflammatory reactions, particularly those involving the vessel wall. PMID- 1429571 TI - The identification of a domain in Escherichia coli elongation factor Tu that interacts with elongation factor Ts. AB - A method has been developed to search for the elongation factor Tu (EF-Tu) domain(s) that interact with elongation factor Ts (EF-Ts). This method is based on the suppression of Escherichia coli EF-Tu-dominant negative mutation K136E, a mutation that exerts its effect by sequestering EF-Ts. We have identified nine single-amino acid- substituted suppression mutations in the region 146-199 of EF Tu. These mutations are R154C, P168L, A174V, K176E, D181G, E190K, D196G, S197F, and I199V. All suppression mutations but one (R154C) significantly affect EF-Tu's ability to interact with EF-Ts under equilibrium conditions. Moreover, with the exception of mutation A174V, the GDP affinity of EF-Tu appears to be relatively unaffected by these mutations. These results suggest that the domain of residues 154 to 199 on EF-Tu is involved in interacting with EF-Ts. These suppression mutations are also capable of suppressing dominant negative mutants N135D and N135I to various degrees. This suggests that dominant negative mutants N135D and N135I are likely to have the same molecular basis as the K136E mutation. The method we have developed in this study is versatile and can be readily adapted to map other regions of EF-Tu. A model of EF-Ts-catalyzed guanine-nucleotide exchange is discussed. PMID- 1429573 TI - Characterization of a gain of function mutation of integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa). AB - Integrin alpha IIb beta 3 (platelet glycoprotein IIb-IIIa) is a prototype of integrins involved in cellular adhesive functions. As part of a structure function analysis of this molecule, we constructed a mutant, designated alpha IIb beta 3 (beta 1-2), by replacing 6 amino acids within a putative ligand binding domain of the beta 3 subunit with sequences derived from beta 1. The alteration did not affect the capacity of beta 3(beta 1-2) to combine with transfected alpha IIb, nor did it cause it to combine with endogenous alpha 5. Integrin alpha IIb beta 3(beta 1-2) was in a "resting" state on Chinese hamster ovary cells as judged by minimal binding of an activation-specific anti-alpha IIb beta 3, PAC1. Nevertheless, cells expressing alpha IIb beta 3(beta 1-2) spontaneously bound fibrinogen with low affinity (Ka = (4.85 +/- 0.84) x 10(6) M-1). Activation with an anti-beta 3 antibody (monoclonal antibody 62) resulted in a 10-fold increase in fibrinogen binding affinity (Ka = (4.55 +/- 0.77) x 10(7) M-1), which was 3 fold greater than fibrinogen binding to activated wild type alpha IIb beta 3 (Ka = (1.66 +/- 0.33) x 10(7) M-1, F = 7.46, p = 0.008). The mutant receptor also bound fibrinogen mimetic peptide ligands with enhanced affinity as measured by the conformation-specific antibody, anti-LIBS1. This indicates that the increased affinity for fibrinogen was caused by enhanced interaction of alpha IIb beta 3(beta 1-2) with known recognition sequences in fibrinogen. Thus, this gain of function mutant augments ligand binding function, supporting a role for this region of the beta subunit in ligand binding to integrins. PMID- 1429572 TI - Tissue factor residues 157-167 are required for efficient proteolytic activation of factor X and factor VII. AB - The cell surface receptor tissue factor (TF) initiates coagulation by supporting the proteolytic activation of factors X and IX as well as VII to active serine proteases. Architectural similarity of TF to the cytokine receptor family suggests a strand-loop-strand structure for TF residues 151-174. Site-directed Ala exchanges in the predicted surface loop demonstrated that residues Tyr157, Lys159, Ser163, Gly164, Lys165, and Lys166 are important for function. Addition of side chain atoms at the Ser162 position decreased function, whereas the Ala exchange was tolerated. The dysfunctional mutants bound VII with high affinity and fully supported the catalysis of small peptidyl substrates by the mutant TF.VIIa complex. Lys159-->Ala substitution was compatible with efficient activation of factor X, whereas the Try157-->Ala exchange and mutations in the carboxyl aspect of the predicted loop resulted in diminished activation of factor X. The specific plasma procoagulant activity of all functionally deficient mutants increased 7- to 200-fold upon the supplementation of VIIa suggesting that TF residues 157-167 also provide important interactions that accelerate the activation of VII to VIIa. These data are consistent with assignment of the TF 157-167 region as contributing to protein substrate recognition and cleavage by the TF.VIIa complex. PMID- 1429574 TI - Selenomethionyl dihydrofolate reductase from Escherichia coli. Comparative biochemistry and 77Se nuclear magnetic resonance spectroscopy. AB - The biosynthetic replacement of Met residues by selenomethionine (SeMet) facilitates the determination of three-dimensional structure by multiwavelength anomalous diffraction (Yang, W., Hendrickson, W. A., Crouch, R.J., and Satow, Y. (1990) Science 249, 1398-1405). In an effort to examine any biochemical effects due to the replacement of Met residues by SeMet, we chose to compare the kinetic and binding properties of selenomethionyl dihydrofolate reductase with those of the wt enzyme. There are 5 Met residues in Escherichia coli dihydrofolate reductase with 2 located in the Met-20 loop, which is a sequence of residues forming a lid over the active site. Utilizing plasmid pWT8, which affords 10-15% soluble protein as E. coli dihydrofolate reductase, we readily isolated both the SeMet and wt enzymes from E. coli DL41 utilizing a novel purification protocol. Both enzymes exhibited essentially the same kinetic and binding properties, including specific activities (45 mumol/min/mg), Km (7,8-dihydrofolate = 0.39 microM; NADPH = 2.0 microM), kcat (13.5/s), and 1:1 noncovalent inhibitory binding ratios with methotrexate. The inhibitory effects of divalent and monovalent cations on activity were also assessed, with the SeMet-containing enzyme exhibiting a uniformly greater sensitivity than the wt enzyme. We conclude that the biochemical properties of dihydrofolate reductase are virtually unperturbed by SeMet inclusion. Analysis of SeMet dihydrofolate reductase by 77Se nuclear magnetic resonance spectroscopy revealed five distinct resonances, thus indicating the potential value of this technique in employing selenium as a nonperturbing NMR probe of protein structure and function. PMID- 1429575 TI - Crystal structure disposition of thymidylic acid tetramer in complex with ribonuclease A. AB - The crystal structure of ribonuclease A with bound thymidylic acid tetramer is reported at 2.5-A resolution. The diffusion of the tetramer into native orthorhombic crystals of the ribonuclease allows for the formation of a structurally stable complex where the single-stranded nucleic acid enters and leaves the enzyme's catalytic region in a persistent 5'-3' direction. The binding of the tetramer to the enzyme's surface is facilitated and mediated by electrostatic interactions between basic protein residues and nucleotide phosphates. Two pyrimidine nucleotides are bound to the enzyme's active site in a manner similar to that observed for other complexes between ribonuclease A and nucleic acid oligomers. PMID- 1429576 TI - Identification of the essential histidine residue at the active site of Escherichia coli dehydroquinase. AB - The shikimate pathway enzyme 3-dehydroquinase is very susceptible to inactivation by the group-specific reagent diethyl pyrocarbonate (DEP). Inactivation follows pseudo first-order kinetics and exhibits a second-order rate constant of 148.5 M 1 min-1. An equilibrium mixture of substrate and product substantially protects against inactivation by DEP, suggesting that residues within the active site are being modified. Complete inactivation of the enzyme correlates with the modification of 6 histidine residues/subunit as determined by difference spectroscopy at 240 nm. Enzymic activity can be restored by hydroxylamine treatment, which is also consistent with the modification occurring at histidine residues. Using the kinetic method of Tsou (Tsou, C.-L. (1962) Sci. Sin. 11, 1535 1558), it was shown that modification of a single histidine residue leads to inactivation. Ligand protection experiments also indicated that 1 histidine residue was protected from DEP modification. pH studies show that the pKa for this inactivation is 6.18, which is identical to the single pKa determined from the pH/log Vmax profile for the enzyme. A single active site peptide was identified by differential peptide mapping in the presence and absence of ligand. This peptide was found to comprise residues 141-158; of the 2 histidines in this peptide (His-143 and His-146), only one, His-143, is conserved among all type I dehydroquinases. We propose that His-143 is the active site histidine responsible for DEP-mediated inactivation of dehydroquinase and is a good candidate for the general base that has been postulated to participate in the mechanism of this enzyme. PMID- 1429578 TI - Bidirectional mechanism of plasma membrane transport of reduced glutathione in intact rat hepatocytes and membrane vesicles. AB - We determined the trans effects of extracellular reduced glutathione (GSH) on the rate of efflux of endogenous labeled GSH from freshly isolated rat hepatocytes. The presence of GSH (10 mM) in the medium significantly stimulated the fractional rate of efflux of [35S]GSH from 5.2 to 12.6%/15 min (p < 0.01). This effect was concentration-dependent, had sigmoid type of kinetics (D50 of 0.32 mM), and was reversible upon removal of external GSH. trans-Stimulation (counter-transport) was also observed with 5 mM oxidized glutathione (GSSG) and ophthalmic acid (fractional [35S] GSH efflux: 13.4% +/- 4.1 and 8.8% +/- 2.3 in 15 min, respectively, compared with control: 4.7 +/- 2.5/15 min). Bromosulphthalein glutathione (BSP-GSH, 5 mM) in Krebs buffer inhibited the fractional [35S]GSH efflux (1.1%/15 min), whereas in Cl(-)-free buffer, GSH efflux was stimulated (14.2%/15 min) compared with control. trans-Stimulation was independent of chloride. BSP-GSH cis-inhibited and trans-stimulated the initial rate of GSH transport in basolateral-enriched membrane vesicles (bLPM) but not in canalicular enriched membrane vesicles (cLPM). gamma-Glutamyl compounds also cis-inhibited and trans-stimulated GSH transport in bLPM vesicles. GSH-depleted hepatocytes incubated with 10 mM [35S]GSH accumulated more GSH than repleted cells, but the initial rate of uptake of radioactivity was faster in repleted cells. In contrast, repleted hepatocytes incubated with tracer or 50 microM [35S]GSH did not take up GSH. Thus, the sinusoidal membrane GSH transporter exhibits low affinity kinetics with sigmoid features for both GSH uptake and trans-stimulation of efflux, explaining the lack of uptake of GSH at low physiologic extracellular concentrations. Therefore, our findings support and explain the widely held view that GSH transport is unidirectional under physiologic conditions. However, the efflux of GSH may also occur in exchange for the uptake of organic anions and gamma-glutamyl compounds. PMID- 1429577 TI - Agonist-induced phosphorylation and desensitization of human m2 muscarinic cholinergic receptors in Sf9 insect cells. AB - The human m1 (hm1) and m2 (hm2) muscarinic cholinergic receptors (mAChR) expressed in Sf9 insect cells using recombinant baculovirus were tested for their ability to undergo agonist-dependent phosphorylation and desensitization. The muscarinic agonist carbachol induced phosphorylation of the hm2 mAChR in the Sf9 cells incubated with 32P(i) to an extent of 4-5 mol of phosphate/mol of receptor. In contrast, no phosphorylation of the hm1 mAChR was observed. The hm2 mAChR stimulated [35S]GTP gamma S binding to, and GTPase activity of, the insect cell G proteins. These receptor-mediated activities were reduced by 50% in membranes prepared from agonist-treated cells compared to control, suggesting that the agonist-induced phosphorylation of the hm2 mAChR resulted in desensitization of the receptors. No role for protein kinase C or cyclic nucleotide-dependent kinases in receptor phosphorylation and desensitization was suggested from studies using agents known to modulate the activity of these enzymes. However, pertussis toxin was found to completely eliminate the interaction of the hm2 receptors with the insect cell G-proteins, but did not perturb the ability of carbachol to induce agonist-dependent phosphorylation of the receptors. These results suggested that G-proteins and/or G-protein-activated signalling were not necessary for the agonist-induced phosphorylation of the receptors. Overall, the data indicated that the human m2 (but not the human m1) mAChR expressed in Sf9 insect cells undergo phosphorylation and desensitization in an agonist-dependent, G-protein-independent fashion by an endogenous insect cell kinase. The results demonstrated that a human G-protein-linked receptor is regulated in insect cells in a manner that is similar to that involving members of the G-protein receptor kinase family. PMID- 1429579 TI - Nucleobase transporter-mediated permeation of 2',3'-dideoxyguanosine in human erythrocytes and human T-lymphoblastoid CCRF-CEM cells. AB - Several 2',3'-dideoxynucleosides (ddNs), agents that inhibit the replication of human immunodeficiency virus and hepatitis B virus, enter mammalian cells by simple diffusion. In this report, we show that the membrane permeation of 2',3' dideoxyguanosine (ddG) in human erythrocytes and CCRF-CEM cells, in contrast with that of other ddNs, is transporter-mediated. Inward fluxes of ddG in both cell types were inhibited by adenine, hypoxanthine, and acyclovir, but not by inhibitors of nucleoside transport (nitrobenzylthioinosine, dipyridamole, dilazep). Fluxes of ddG in human erythrocytes were attributable to a single, rate saturable process (Km, 380 +/- 90 microM and Vmax, 7.9 +/- 0.8 pmol/s/microliter cell water) that was competitively inhibited by adenine (Ki, 16 microM). These results showed that ddG entered human erythrocytes and CCRF-CEM cells by a transporter-mediated process that was also the basis for entry of purine nucleobases. In contrast, inward fluxes of 2,6-diaminopurine-2',3' dideoxyriboside (ddDAPR), a prodrug of ddG, were not affected by purine nucleobases or nucleoside transport inhibitors in either cell type. Thus, the permeation properties of ddDAPR resembled those of 2',3'-dideoxyadenosine, a diffusional permeant (cell uptake is transporter-independent), and contrasted with those of ddG, the deamination product of ddDAPR. This study demonstrated that the nucleobase moiety of ddNs is an important determinant of membrane permeation. PMID- 1429580 TI - Stopped-flow kinetic study of vitamin E regeneration reaction with biological hydroquinones (reduced forms of ubiquinone, vitamin K, and tocopherolquinone) in solution. AB - A kinetic study of the regeneration reaction of vitamin E (tocopherol) with eight biological hydroquinones (HQs) (ubiquinol-10 (Q10H2 1); ubiquinol-0 (Q0H2 2); vitamin K1 HQ (VK1H2 3); vitamin K3 HQ (VK3H2 4); alpha-, beta-, and gamma tocopherol-HQs (alpha-, beta-, and gamma-TQH2 5-7); and 2,3,5-trimethyl-1,4-HQ (TMQH2 8)) in solution was performed. The second-order rate constants (k4) for the reaction of HQs 1-8 with alpha-tocopheroxyl and 5,7-diisopropyltocopheroxyl radicals in ethanol, benzene, and isopropyl alcohol/water (5:1, v/v) solutions were measured with a stopped-flow spectrophotometer. The order of magnitude of k4 values obtained for HQs is VK1H2 > VK3H2 > alpha-TQH2 > beta-TQH2 approximately gamma-TQH2 approximately TMQH2 > Q10H2 > Q0H2, being independent of the kinds of tocopheroxyl radicals and the polarity of the solvents. The log of the k4 values obtained for HQs was found to correlate with their peak oxidation potentials. Comparing the k2 value (2.68 x 10(6) M-1 s-1 obtained for the reaction of alpha tocopheroxyl with vitamin C (sodium ascorbate) with those (k4 = 2.54 x 10(5) and 8.15 x 10(5) M-1 s-1) obtained for the reaction of alpha-tocopheroxyl with Q10H2 and alpha-TQH2 in isopropyl alcohol/water mixtures, the former is approximately 11 and 3 times as reactive as the latter, respectively. On the other hand, the k2 value obtained for sodium ascorbate is smaller than the k4 values obtained for VK1H2 and VK3H2. These results suggest that mixtures of vitamin E and these HQs (as well as those of vitamins E and C) may function synergistically as antioxidants in various tissues and mitochondria. PMID- 1429581 TI - Identification of xenin, a xenopsin-related peptide, in the human gastric mucosa and its effect on exocrine pancreatic secretion. AB - One of the peptides previously discovered in amphibians is the octapeptide xenopsin. As immunohistochemistry has also indicated the presence of xenopsin immunoreactivity in man, we extracted in the present investigation xenopsin immunoreactive material from human gastric mucosa and purified it to homogeneity with several high performance liquid chromatography (HPLC) reverse phase and ion exchange chromatographic steps. The eluates were monitored with a radioimmunoassay for amphibian xenopsin. Determination of the amino acid sequence revealed a 25-amino acid peptide having 6 C-terminal amino acids in common with amphibian xenopsin. The sequence of this peptide, termed xenin 25, is M-L-T-K-F-E T-K-S-A-R-V-K-G-L-S-F-H-P-K-R-P-W-I-L. The peptide was custom-synthesized. Mass spectrometry of the synthetic and the extracted peptide revealed identical molecular mass. Purification of 250 ml of human postprandial plasma with Sep-Pak C18 cartridges, reverse phase HPLC, and ion exchange chromatography demonstrated circulating xenin immunoreactivity at a retention time identical to xenin 25. The amount of xenin immunoreactivity at the position of xenin 25 on C18-HPLC increased significantly after a meal. A radioimmunoassay utilizing antibodies to xenin 25 and a 125I-labeled analogue of xenin 25 was used to measure immunoreactive xenin in the plasma of 10 volunteers. There was a significant rise of xenin immunoreactivity in the plasma after a meal. Intravenous infusion of the synthetic peptide in dogs stimulated exocrine pancreatic secretion beginning at a dose of 4 pmol/kg/min. The maximal effect was seen with 64 pmol/kg/min. We have detected, therefore, a new peptide, xenin 25, in human gastric mucosa; we have provided evidence for the presence of this peptide in the human circulation, and have shown a rise of plasma xenin concentrations after a meal. This peptide stimulates exocrine pancreatic secretion. Its physiologic role deserves further investigation. PMID- 1429582 TI - Affinity purification and characterization of myristoylated alanine-rich protein kinase C substrate (MARCKS) from bovine brain. Comparison of the cytoplasmic and the membrane-bound forms. AB - A major in vivo substrate of Ca(2+)-phospholipid-dependent protein kinase (myristoylated alanine-rich C-kinase substrate (MARCKS)) has been purified to apparent homogeneity from the particulate as well as from the cytoplasmic fractions of calf brain using a calmodulin affinity column. The two preparations were characterized and compared with various biochemical and biophysical techniques. Although they behave similarly in various chromatographic procedures during purification, their elution positions from the gel filtration column are markedly different. Stokes radii of 85 and 45 A were measured for the cytoplasmic and membrane MARCKS, respectively. Once purified, however, they show a similar small Stokes radius (45 A), suggesting the dissociation of a component or a drastic conformational change in the cytoplasmic preparation during purification. The electrospray mass spectroscopic analysis of the two preparations revealed the existence of at least three major subpopulations with molecular mass differences of 80 daltons, which suggests the presence of protein phosphorylated in different degrees. The cytoplasmic preparation contains more phosphorylated species compared with the membrane preparation, whereas the calculated molecular weight of each peak was indistinguishable between the two preparations. Correspondingly, when the two preparations were phosphorylated by purified protein kinase C in vitro, more phosphate groups were transferred to the membrane preparation (4 mol/mol) than to the cytoplasmic preparation (2.9 mol/mol). A significant difference was also observed in the inhibition of calmodulin of the phosphorylation reaction. On the other hand, the circular dichroism of the two preparations showed similar spectra rich in random coil with little contribution of alpha-helix (approximately 10%), suggesting that there is not a significant difference in the overall conformation. These results clearly established that the two preparations are the same protein coded by a single gene but they differ in their degree of phosphorylation, and that the difference observed in their Stokes radius is due to the presence of an unidentified factor that is removed from the cytoplasmic MARCKS during purification. PMID- 1429583 TI - Kinetics of Ca2+ release and contraction induced by photolysis of caged D-myo inositol 1,4,5-trisphosphate in smooth muscle. The effects of heparin, procaine, and adenine nucleotides. AB - The kinetics of Ca2+ release and contraction induced by photolytic release of inositol 1,4,5-trisphosphate (InsP3) were determined in permeabilized smooth muscle. The rate of Ca2+ release was half-maximal at 1 microM InsP3. The concentration-dependent delay of Ca2+ release at saturating InsP3 concentration was approximately 10 ms and within the uncertainty of the measurements. The relationship between the delay and InsP3 concentration showed no evidence of a high level (n = 4 or higher) of cooperativity but could not distinguish between no cooperativity (n = 1) or a low level (n = 2) of cooperativity. Submaximal [InsP3] caused only partial Ca2+ release from the InsP3-sensitive stores. InsP3 induced Ca2+ release was markedly potentiated by ATP or by adenosine 5' (beta,gamma-methylene-triphosphate), but neither the rate nor the amplitude of release was significantly affected by procaine (2-5 mM). Heparin increased the delay between photolysis and Ca2+ release, indicating that the off rate of inert ligand(s) bound to InsP3 receptors may contribute to the physiological delay in Ca2+ release. There was a much longer (370 ms +/- 45 S.E.) delay between the rise of Ca2+ and force development, presumably reflecting events preceding and associated with myosin light chain phosphorylation. PMID- 1429584 TI - Phosphate transport by capillaries of the blood-brain barrier. AB - Capillaries were isolated from bovine brain cortex and used for phosphate transport studies. The influx of phosphate through capillary membranes was studied by incubation with [32Pi]phosphate followed by a rapid filtration technique. Phosphate uptake by brain capillaries was mediated by a saturable high affinity system which is independent of the sodium concentration in the incubation medium. The apparent half-saturation constant (Km) and maximal influx (Vmax) were estimated to 160 microM and 0.37 nmol/mg protein/30 s. Transport was inhibited by the phosphate analogues arsenate and phosphonoformic acid with apparent inhibition constants of 5 and 11 mM, respectively. The metabolic inhibitors cyanide and ouabain had no effect on the transport activity. Competition experiments showed that phosphate uptake was inhibited up to 41% by various anions (pyruvate, acetate, citrate, glutamate, and sulfate). In addition, phosphate uptake was significantly decreased by two selective inhibitors of anionic exchangers, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and 4 acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid. Chloride was not a substrate of the phosphate carrier as the replacement of external chloride, by nitrate, thiocyanate, or gluconate, did not increase phosphate transport. Aminohippuric acid and N'-methylnicotinamide, two specific substrates of anionic and cationic drug exchangers, did not compete with the phosphate carrier of cerebral capillaries. However, trans-stimulation with bicarbonate increased phosphate transport by 28%, and this stimulation was inhibited by 1 mM 4,4' diisothiocyanostilbene-2,2'-disulfonic acid, suggesting that the carrier of the cerebral capillaries could exchange phosphate with bicarbonate. PMID- 1429585 TI - Glutaraldehyde cross-links Lys-492 and Arg-678 at the active site of sarcoplasmic reticulum Ca(2+)-ATPase. AB - It has been shown previously that glutaraldehyde cross-links the Ca(2+)-ATPase of sarcoplasmic reticulum intramolecularly at the active site, involving residues participating in nucleotide binding and the conformational change that results in Ca2+ release to the vesicle lumen and formation of ADP-insensitive E2-P (Ross, D. C., Davidson, G. A., and McIntosh, D. B. (1991) J. Biol. Chem. 266, 4613-4621). This study shows that 10 nmol of [14C]glutaraldehyde/mg of protein attached irreversibly to the ATPase under conditions optimal for formation of the intramolecular cross-link. Half of this amount (i.e. 1 mol/mol ATPase) was inhibited by nucleotide binding. Thermolysin digestion of derivatized vesicles released two nucleotide-sensitive 14C-labeled species, which were isolated and identified as FSRDR*S AND FSRDR*S FA* FA*VEPS where the missing residues are Lys 492 and Arg-678. The majority of the 14C label was released in the sixth cycle of both Edman degradations, confirming the cross-link position. Lys-492 and Arg-678 are evidently close together in the active site, but their distance apart in the linear sequence suggests that they may arise from separate domains, which together constitute an ATP binding cleft. Residues in both regions, and Lys-492 in particular (McIntosh, D.B., Woolley, D.G., and Berman, M.C. (1992) J. Biol. Chem. 267, 5301-5309), have been derivatized by nucleotide-based affinity probes. Mutations of both of these residues in some of the bacterial P-type ATPases suggest that they do not play an essential catalytic role, and the inability of the cross-linked ATPase to form E2-P and to release Ca2+ to the lumen is probably because an essential tertiary structural movement at the active site is blocked. PMID- 1429586 TI - The CCAAT/enhancer-binding protein trans-activates the human cholesteryl ester transfer protein gene promoter. AB - The plasma cholesteryl ester transfer protein (CETP), primarily synthesized in the liver of several species, is expressed at very low levels in a number of transformed human liver cell lines. The human CETP gene promoter contains a sequence that closely resembles the binding site for the transcription factor CCAAT/enhancer-binding protein (C/EBP). This site is capable of binding C/EBP, as shown by electrophoretic mobility shift and DNase I footprint analyses. Transient expression of the bacterial chloramphenicol acetyltransferase gene under the control of the human CETP gene promotor gave low activities in the human hepatoma cell line, HepG2. However, in the presence of C/EBP, CAT activity was markedly elevated indicating that CETP gene promoter activity was enhanced. In primary cultures of isolated hepatocytes, CETP mRNA was lost rapidly and in parallel with the C/EBP mRNA. C/EBP may play an important role in the proper maintenance of CETP gene promoter activity, and its low levels in proliferating or cultured cells may account for the low level of the CETP gene expression in immortalized human liver cell lines or cultured hepatocytes. PMID- 1429587 TI - COMP (cartilage oligomeric matrix protein) is structurally related to the thrombospondins. AB - Cloning and sequence analysis of cartilage oligomeric matrix protein (COMP) cDNA, representing a cartilage pentameric protein, revealed a protein of 755 amino acid residues with a calculated molecular mass of 82,700 Da. Expression of the cDNA in COS cells showed that COMP is a homopolymer composed of five identical disulfide linked subunits. COMP is homologous to the carboxyl-terminal half of thrombospondin, and the homologies include 89% and 54% of the residues in COMP and thrombospondin, respectively. The similarities are most pronounced in the carboxyl-terminal domains and in the calcium binding type 3 repeat domains in which about 60% of the amino acid residues are identical. In the type 2/epidermal growth factor repeat domains the two proteins contain 41% identical residues. The sequence of the amino-terminal 84-amino acid residues is unique for COMP. Comparison of the amino acid sequences in the type 2 and type 3 repeat domains of COMP and the thrombospondins shows that COMP is the product of a unique gene and not the result of an alternatively spliced thrombospondin gene. PMID- 1429588 TI - Insertion of an intracisternal A particle within the 5'-regulatory region of a gene encoding folate-binding protein in L1210 leukemia cells in response to low folate selection. Association with increased protein expression. AB - We have previously described a subline of L1210 murine leukemia cells (LL1) selected in a low level of 5-formyltetrahydrofolate which overexpresses a membrane-bound folate-binding protein (FBP1) and exhibits a rearrangement at the locus encoding this protein. Genomic clones containing the entire FBP1-encoding DNA from both L1210 and LL1 were isolated and characterized. Sequence analysis indicates that, with exception of the 5'-region, the FBP1-encoding locus in both cell lines is identical. The rearrangement in LL1 results from the insertion of an intracisternal A particle (IAP) in the head-to-head (antisense) orientation 72 base pairs (bp) upstream of the FBP1 ATG start codon. The IAP likely provides an alternative promoter for FBP1 expression which may produce a novel transcript with enhanced stability. Presence of the IAP appears to inactivate or relocate normal cis-acting regulatory sequences as expression of the FBP1 transcript in LL1 is not regulated by the folate status of the cell. PMID- 1429589 TI - Enzymatic transfer of a preassembled trisaccharide antigen to cell surfaces using a fucosyltransferase. AB - The Lewis alpha (1-->3/4)-fucosyltransferase (Le-FucT) is known to fucosylate both Type I (beta Gal(1-->3) beta GlcNAc) and Type II (beta Gal(1-->4) beta GlcNAc) sequences even when these are sialylated at OH-3 or fucosylated at OH-2 of the terminal Gal residues. These acceptor sequences are ubiquitous on mammalian cell-surface glycoproteins and glycolipids. The Le-FucT enzyme is therefore a potential candidate as a universal reagent for the modification of cell surfaces. We have found that a readily accessible, partially purified Le FucT from human milk, which normally uses GDP-fucose (a 6-deoxy sugar) as the donor for the transfer of a single fucose residue, will also transfer a fucose residue substituted on C-6 by a very large sterically demanding structure, in this instance, a synthetic blood group antigen. As a demonstration of the ability of the Le-FucT to modify glycoconjugates in a mild and specific manner, we chemically synthesized the complex sugar-nucleotide alpha Gal(1-->3) [alpha Fuc(1 ->2)]-beta Gal-O-(CH2)8COHN(6)-beta-L-fucose-GDP (13) which is a GDP-fucose analog where the human blood group B trisaccharide antigen is covalently linked to C-6 of fucose through an amino group. It is shown that, in enzyme-linked immunosorbent assays, the Le-FucT uses both immobilized beta Gal(1-->3) beta GlcNAc-bovine serum albumin conjugates and fetuin as acceptor substrates and renders them blood group B-active as detected by a monoclonal anti-B blood grouping antibody. The fucose residue to which the B-trisaccharide is linked therefore becomes covalently attached to the acceptor oligosaccharide chains of those glycoproteins. Incubation of type "O" erythrocytes with the Le-FucT and complex donor 13 results in the covalent transfer of alpha Gal(1-->3) [alpha Fuc(1-->2)] beta Gal-O-(CH2)8COHN(6)-beta-L-Fuc to cell-surface acceptors since the cells become phenotypically "B" and are agglutinated by the same antibody. It is proposed that the Le-FucT represents a powerful new tool with the ability to label animal cell surfaces with preassembled oligosaccharide and possibly also other complex recognition markers. PMID- 1429590 TI - Purification of an 11 S regulator of the multicatalytic protease. AB - We have identified and purified a protein complex from human red blood cells that activates the multicatalytic protease (MCP). The complex, which we call the regulator, sediments at 11 S and is composed of 30-kDa subunits. The regulator does not hydrolyze fluorogenic peptides, but when multicatalytic protease and regulator are combined, MCP cleaves succinyl-Leu-Leu-Val-Tyr-7-amido-4 methylcoumarin and Leu-Leu-Glu-p-nitroanilide as much as 60-fold faster. Hydrolysis of several other fluorogenic peptides is stimulated to a lesser extent, and activated MCP does not degrade ubiquitin-lysozyme conjugates, bovine serum albumin, or lysozyme. Latent and activated forms of MCP display similar sensitivity to protease inhibitors, suggesting that activation does not generate new kinds of catalytic sites. In addition, ATP suppresses peptide hydrolysis by activated and latent MCPs to the same extent. Activation involves binding of regulator to MCP, and activated MCP migrates slower on native acrylamide gels. Dissociation of the MCP regulator complex during prolonged sedimentation on glycerol gradients releases active regulator and MCP molecules capable of being reactivated. Moreover, two-dimensional electrophoresis does not reveal changes in MCP or regulator subunits following activation. Thus, activation appears to result from reversible association of regulator subunits with MCP. PMID- 1429591 TI - Site-specific frameshift mutagenesis by a propanodeoxyguanosine adduct positioned in the (CpG)4 hot-spot of Salmonella typhimurium hisD3052 carried on an M13 vector. AB - Malondialdehyde induces frameshift mutations in Salmonella typhimurium strain hisD3052. The ability of propanodeoxyguanosine (PdG), a structural analog of the major malondialdehyde-deoxyguanosine adduct, to induce site-specific frameshift mutations was tested in the (CpG)4 hot-spot of hisD3052 carried on an M13 vector (M13MB102). PdG was introduced at position 6248 of duplex M13MB102 by ligation of the oligonucleotide 5'-CGC(PdG)CGGCATG-3' into a heteroduplex containing an 11 nucleotide gap in the (-)-strand between the SphI and BssHII restriction sites and deoxyuridine in place of thymidine in the (+)-strand. Ligation proceeded with 70% efficiency, and closed circular duplex DNA molecules were isolated in 40% yield. The adducted genome was sensitive to cleavage by SphI but resistant to cleavage by BssHII. Transformation of Escherichia coli strain JM105 with adducted M13MB102 led to 25% reduced survival relative to unadducted M13MB102 and produced frameshift mutations in 2.5% of the progeny phage. All of the mutations were deletions, and 70% occurred by deletion of CpG. Unadducted genomes exhibited a 40 fold lower mutation frequency, and all the mutations were single-base deletions at the sites of ligation of the 11-mer. These results illustrate that PdG, a structural analog of the major malondialdehyde-deoxyguanosine adduct, induces frameshift mutations in M13MB102 and that single-stranded nicks are efficient premutagenic lesions in this recombinant bacteriophage. PMID- 1429592 TI - The post-translational processing and intracellular sorting of PC2 in the islets of Langerhans. AB - Proinsulin conversion in the insulin secretory granule is mediated by two sequence-specific endoproteases related to the Kex2 homologues, PC2 and PC3 (Bennett, D. L., Bailyes, E. M., Nielsen, E., Guest, P. C., Rutherford, N. G., Arden, S. D., and Hutton, J. C. (1992) J. Biol. Chem. 267, 15229-15236; Bailyes, E. M., Bennett, D. L., and Hutton, J. C. (1992) Enzyme, in press). Radiolabeling studies using isolated rat islets showed that PC2 was synthesized initially as a 76-kDa glycoprotein which was converted by limited proteolysis to the mature 64 66-kDa form. Conversion was initiated approximately 1 h after synthesis and proceeded via intermediates of 71, 68, and 66 kDa with a t1/2 of 140 min. Release of only the 66- and 64-66-kDa radiolabeled forms of PC2 was induced by glucose and then only at times more than 2 h following synthesis. Proinsulin conversion, by contrast, was more rapid (delay = 30 min, t1/2 = 60 min), and release commenced as soon as 1 h after synthesis with the secreted material being comprised of the precursor, intermediate, and mature forms of insulin. Ultrastructural analysis of islet beta cells showed that PC2 was concentrated in secretory granules. Subcellular fractionation combined with immunoblot analysis showed that insulinoma secretory granules contained only the mature 64-66-kDa form of PC2, whereas fractions enriched in Golgi and endoplasmic reticulum contained a mixture of the 76- and 66-kDa forms of the enzyme. These results indicate that post-translational proteolysis of PC2 is initiated before sorting into the regulated pathway of secretion and that the relative proportions of proinsulin and PC2 packaged into secretory granules will change with physiological conditions. PMID- 1429593 TI - Molecular cloning of AMP deaminase isoform L. Sequence and bacterial expression of human AMPD2 cDNA. AB - Human AMPD2 cDNA clones have been isolated from T-lymphoblast and placental lambda gt11 libraries utilizing a previously cloned rat partial AMPD2 cDNA as the probe. Alignment analysis of all cDNA clones indicates the presence of intervening sequences in several placental isolates. This has been confirmed by sequencing human AMPD2 genomic clones. Intervening sequences can be removed from the cDNA clones by restriction with endonucleases at unique sites within the proposed open reading frame. This results in a 3292-base pair cDNA proposed to contain the entire AMPD2 open reading frame, which would encode a 760-amino acid polypeptide with a predicted subunit molecular mass of 88.1 kDa. Nucleotide and predicted amino acid comparisons with the 264 base pairs of proposed coding sequences in the rat AMPD2 cDNA demonstrate 91% similarity and identity, respectively. A comparison of the predicted human AMPD1 and AMPD2 polypeptides demonstrates homology in their C-terminal domains. Included in this region is the conserved motif, SLSTDDP, proposed to be part of the catalytic site of all AMP deaminases. In contrast, the predicted N-terminal domains of the human AMPD1 and AMPD2 polypeptides are unique. When placed in a prokaryotic expression vector, the human AMPD2 cDNA expresses AMP deaminase activity which can be precipitated with polyclonal antisera specific for isoform L. PMID- 1429594 TI - In vitro catalysis of oxidative folding of disulfide-bonded proteins by the Escherichia coli dsbA (ppfA) gene product. AB - It was shown previously that the Escherichia coli gene ppfA (dsbA) encodes a periplasmic protein, and its inactivation leads to a deficiency in disulfide bond formation of envelope proteins (Kamitani, S., Akiyama, Y., and Ito, K. (1992) EMBO J. 11, 57-62; Bardwell, J. C. A., McGovern, K., and Beckwith, J. (1991) Cell 67, 581-589). The DsbA/PpfA protein was overproduced, purified, and examined for its activities in vitro. Its abundance in a wild-type cell was estimated to be about 850 molecules which probably exist as homodimers as suggested by size exclusion chromatography. Purified DsbA markedly stimulated disulfide bond formation of E. coli alkaline phosphatase, either in vitro synthesized or purified and denatured, as well as of reduced bovine ribonuclease A. The DsbA catalyzed rapid disulfide bond formation occurred after a lag period which appeared to be determined by the redox state of the reaction mixture and concentration of DsbA. Inclusion of higher concentrations of oxidized glutathione or DsbA shortened the lag period. We propose that DsbA, which proved to directly catalyze disulfide bond formation, may also have a role in maintaining the bacterial periplasm oxidative. PMID- 1429595 TI - A macrophage Fc receptor for IgG is also a receptor for oxidized low density lipoprotein. AB - The internalization of oxidized low density lipoprotein (OxLDL) by macrophages is hypothesized to contribute to foam cell formation and eventually to atherosclerotic lesion formation. OxLDL is a ligand for the acetylated low density lipoprotein (AcLDL) receptor, however, our data show that this receptor accounts for less than half of OxLDL uptake by mouse macrophages, suggesting additional receptors for OxLDL. We have developed a novel expression cloning strategy in order to isolate clones encoding OxLDL receptors. In addition to the AcLDL receptor, we isolated a molecular clone for a structurally unrelated receptor capable of mediating the high affinity uptake of OxLDL following transfection into cells. This receptor has been identified as the mouse Fc gamma RII-B2, a member of a family of receptors known to mediate immune complex uptake through recognition of the Fc region of IgG. The uptake of OxLDL by cells transfected with the Fc gamma RII-B2 clone is not blocked by AcLDL but is blocked by the anti-Fc gamma RII monoclonal antibody, 2.4G2. PMID- 1429597 TI - Transcriptional cross-talk: nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun. AB - The proteins Fos and Jun dimerize to constitute the transcription factor AP-1 which is known to respond to treatment with phorbol esters. AP-1 binds to 12-O tetradecanoylphorbol-13-acetate-responsive elements (TREs) palindromic sequences. cAMP-responsive elements (CREs) are very similar to TREs and CRE-binding proteins are similar in structure to Fos and Jun. Thus, the two main signal transduction pathways have closely related nuclear effectors which could possibly overlap and/or cross-talk. The gene CRE modulator (CREM) encodes both antagonists and an activator of the cAMP transcriptional response by alternative splicing. In this report we show that CREM antagonists are able to block the transcriptional activation elicited by c-Jun. The mechanism by which this repression is obtained does not require heterodimerization between CREM and the Fos and/or Jun proteins. In contrast, we show that both CREM and CRE-binding proteins (CREB) are able to bind TREs and therefore compete with c-Jun for this site. Removal of the phosphorylation domain in CREM does not affect the down-regulatory function. We also show that c-Fos does not affect the inhibitory function of CREM on c-Jun and that the transcriptional activation elicited by the other members of the jun family (JunB, JunD, and v-Jun) is also down-regulated by CREM. PMID- 1429596 TI - Isolation, cDNA cloning, and characterization of an 18-kDa hemagglutinin and amebocyte aggregation factor from Limulus polyphemus. AB - An 18-kDa hemagglutinin which possesses the property of inducing both aggregation of amebocytes and agglutination of erythrocytes has been isolated from Limulus polyphemus amebocytes and purified by ion exchange chromatography. This nonglycosylated, single chain polypeptide with an M(r) of 18,506 and isoelectric point of 8.3 is stored exclusively in the large secretory granules of amebocytes. Based on the partial N-terminal amino acid sequence of 63 residues, DNA probes have been synthesized for screening a pBR322 cDNA library constructed from Limulus amebocytes. The cDNA coding for this protein reveals the presence of a 19 residue signal peptide preceding the 153-residue open reading frame. Northern blot analysis indicates the presence of a single mRNA species. The primary structure derived from the corresponding cDNA sequence reveals an internal homology consisting of two consensus sequences, Val-Asn-Asp/Ser-Trp-Asp and Glu Asp-Arg-Arg-Trp. The formation of 5 disulfide bonds between 10 half-cysteines divides the molecule into three looped domains each containing the Glu-Asp-Arg Arg-Trp repeating unit. One of the novel features of this protein is that it shares 37% identity with a 22-kDa mammalian extracellular matrix protein isolated from fetal bovine skin (Neame, P.J., Choi, H.U., and Rosenberg, L.C. (1989) J. Biol. Chem. 264, 5474-5479). The two proteins exhibit a similar pattern of looped domains, each domain containing a homologous consensus sequence (i.e. Glu-Asp-Arg Arg-Trp). The overall structure of both proteins seems to be highly related, with the exception of an N-terminal tyrosine-rich region present only in the mammalian extracellular matrix protein. The functional properties of the two proteins are similar in that the Limulus 18-kDa protein agglutinates horse erythrocytes and aggregates Limulus amebocytes, and the mammalian 22-kDa protein is an effective adhesion promoter for dermal fibroblasts. On the basis of these unique properties, the newly characterized hemagglutinin has been termed Limulus 18K agglutination-aggregation factor (18K-LAF). PMID- 1429598 TI - Mass spectrometric analysis of the HMGY protein from Lewis lung carcinoma. Identification of phosphorylation sites. AB - The primary structure of the Lewis lung carcinoma protein HMGY belonging to the nuclear group of proteins HMGI (high mobility group I) was determined using electrospray and fast atom bombardment mass spectrometry. It was demonstrated that the sequence of the tumor protein corresponds to the amino acid sequence derived from the cDNA from cultured cells and that the N-terminal serine residue is N-acetylated. Moreover, the two high performance liquid chromatography purified forms Y1 and Y2 of the protein HMGY were shown to differ at the level of serine phosphorylation, since they contain three phosphate and two phosphate groups, respectively, in the C-terminal region. No other modification was detected in the remaining part of the molecule. PMID- 1429599 TI - Activation of protein kinase C accelerates internalization of transferrin receptor but not of major histocompatibility complex class I, independent of their phosphorylation status. AB - Phosphorylation of membrane glycoproteins has often been invoked as a determinant of receptor internalization and receptor trafficking in a more general sense. Here we have studied the trafficking of major histocompatibility complex (MHC) Class I molecules and transferrin receptor (Tfr) related to their phosphorylation status in the human lymphoblastoid cell line JY. High resolution isoelectric focusing (IEF) allows the visualization of phosphorylated and non-phosphorylated protein species simultaneously, using protein backbone-labeling. Analysis on IEF was combined with a neuraminidase protection assay, in which sialic acid modification of the N-linked glycans present on Tfr and Class I molecules is used as a reporter group for cell surface expression. Phosphorylation of Class I heavy chains and Tfr was induced by exposure of cells to the phorbol ester tetradecanoyl phorbol acetate. We show that 1) phosphorylation of MHC Class I molecules is restricted to the cell surface fraction, 2) phosphorylation of MHC Class I molecules by protein kinase C (PKC) is not correlated with their internalization, as no internalization of Class I molecules, phosphorylated or non-phosphorylated, could be detected, 3) the initial rate, but not the final extent of the internalization of Tfr is affected by activation of PKC, and 4) phosphorylated Tfr behaves in a manner identical to non-phosphorylated Tfr in terms of internalization. The effect of activation of PKC on internalization of Tfr therefore most likely takes place at the level of the internalization machinery. Our data concerning the internalization of MHC Class I molecules contrast with earlier studies describing constitutive internalization in the B lymphoblastoid cell line A 46 and in HPB-ALL cells. PMID- 1429600 TI - Initiation of DNA replication in ColE1 plasmids containing multiple potential origins of replication. AB - We have investigated the frequency of replication origin usage in bacterial plasmids containing more than one potential origin. Escherichia coli recA- cells were selectively transformed with pBR322 monomers, dimers, or trimers. Plasmid DNA was isolated and digested with a restriction enzyme that cut the monomer only once, and the replicative intermediates (RIs) were analyzed by neutral/neutral two-dimensional agarose gel electrophoresis. Evidence for initiation outside the linearized plasmid was found only for oligomers. Moreover, in dimers, the intensity of the signal indicative for external initiation was equivalent to that reflecting internal initiation, whereas it was approximately twice as strong in trimers. To determine whether initiation could occur simultaneously at two origins in a single plasmid, we studied the replication of a neodimer in which both units could be unambiguously distinguished. The results showed that although both origins were equally competent to initiate replication, only one was active per plasmid. These observations strongly suggest that in ColE1 plasmids, replication initiates at a single site even when there are several identical potential origins per plasmid. In addition to the conventional two-dimensional gel patterns, novel specific patterns were observed with intensities that varied from one DNA sample to another. These unique patterns were the result of breakage of the RIs at a replication fork. This type of breakage changes both the mass and shape of RIs. When the entire population of RIs is affected, a new population of molecules is formed that may generate a novel pattern in two-dimensional gels. PMID- 1429601 TI - Characterization of the Escherichia coli uracil-DNA glycosylase.inhibitor protein complex. AB - The Bacillus subtilis bacteriophage PBS2 uracil-DNA glycosylase inhibitor (Ugi) protein was characterized and shown to form a stable complex with Escherichia coli uracil-DNA glycosylase (Ung). As determined by mass spectrometry, the Ugi protein had a molecular weight of 9,474. We confirmed this value by sedimentation equilibrium centrifugation and determined that Ugi exists as a monomeric protein in solution. Amino acid analysis performed on both Ugi and Ung proteins was in excellent agreement with the amino acid composition predicted from the respective nucleotide sequence of each gene. The Ung.Ugi complex was resolved from its constitutive components by nondenaturing polyacrylamide gel electrophoresis and shown to possess a 1:1 stoichiometry. Analytical ultracentrifugation studies revealed that the Ung.Ugi complex had a molecular weight of 35,400, consistent with the complex containing one molecule each of Ung and Ugi. The acidic isoelectric points of the protein species were 6.6 (Ung) and 4.2 (Ugi), whereas the Ung.Ugi complex had an isoelectric point of 4.9. Dissociation of the Ung.Ugi complex by SDS-polyacrylamide gel electrophoresis revealed no apparent alteration in the molecular weight of either polypeptide subsequent to binding. Furthermore, when the Ung.Ugi complex was treated with urea and resolved by urea polyacrylamide gel electrophoresis, both uracil-DNA glycosylase and inhibitor activities were recovered from the dissociated complex. Thus, the complex seems to be reversible. In addition, we demonstrated that the Ugi interaction with Ung prevents enzyme binding to DNA and dissociates uracil-DNA glycosylase from a preformed DNA complex. PMID- 1429602 TI - An amino acid substitution (Gly853-->Glu) in the collagen alpha 1(II) chain produces hypochondrogenesis. AB - The spondyloepiphyseal dysplasia subclassification of bone dysplasias includes achondrogenesis, hypochondrogenesis, and spondyloepiphyseal dysplasia congenita. The phenotypic expression of these disorders ranges from mild to perinatal lethal forms. We report the detection and partial characterization of a defect in type II collagen in a perinatal lethal form of hypochondrogenesis. Electrophoresis in sodium dodecyl sulfate-polyacrylamide of CB peptides (where CB represents cyanogen bromide) from type II collagen of the diseased cartilage showed a doublet band for peptide alpha 1(II)CB10 and evidence for post-translational overmodification of the major peptides (CB8, CB10, and CB11) seen as a retarded electrophoretic mobility. Peptide CB10 was digested by endoproteinase Asp-N; and on reverse-phase high pressure liquid chromatography, fragments of abnormal mobility were noted. Sequence analysis of a unique peptide D12 revealed a single amino acid substitution (Gly-->Glu) at position 853 of the triple helical domain. This was confirmed by sequence analysis of amplified COL2A1 cDNA, which revealed a single nucleotide substitution (GGA-->GAA) in 5 of 10 clones. Electron micrographs of the diseased cartilage showed a sparse extracellular matrix and chondrocytes containing dilated rough endoplasmic reticulum, which suggested impaired assembly and secretion of the mutant protein. This case further documents the molecular basis of the spondyloepiphyseal dysplasia spectrum of chondrodysplasias as mutations in COL2A1. PMID- 1429603 TI - Identification of a novel type of processing sites in the precursor for the sea anemone neuropeptide Antho-RFamide (6Gal beta 1-1Cer and cholinephosphoryl-->6Gal beta 1 6Gal beta 1-1Cer. Although the oligosaccharide structures of both PGL1 and PGL2 have previously been found in other organisms, the presence of a choline phosphate group as an oligosaccharide substituent is the first finding in nature. The main molecular species of the ceramide moieties were composed of beheninyl- and lignocerinyloctadecasphingenines and their nonadecasphingenine homologues. PMID- 1429610 TI - Distinct steps in the penetration of adenylate cyclase toxin of Bordetella pertussis into sheep erythrocytes. Translocation of the toxin across the membrane. AB - Adenylate cyclase (AC) toxin from Bordetella pertussis penetrates eukaryotic cells and upon activation by calmodulin generates unregulated levels of intracellular cAMP. The process of toxin penetration into sheep erythrocytes was resolved into three consecutive steps including insertion, translocation, and intracellular cleavage. Insertion of the toxin into the cell membrane occurred over a wide temperature range (4-36 degrees C). In contrast, translocation of the toxin, i.e. transfer of the NH2-terminal catalytically active fragment across the membrane, occurred only above 20 degrees C and was highly temperature-dependent. While a single exposure of the toxin to Ca2+ was sufficient for its insertion into the plasma membrane, toxin translocation required exogenous Ca2+ at mM concentrations. Translocation was not affected by pretreatment of cells with trypsin, N-ethylmaleimide, and sodium carbonate at alkaline pH. The NH2-terminal fragment of the toxin was cleaved in the cell releasing the 45-kDa active AC into the cytosol. The cleavage was blocked by treatment of cells with N ethylmaleimide. It is hypothesized that the COOH-terminal portion of the toxin creates in the membrane a channel through which the NH2-terminal fragment is translocated. PMID- 1429611 TI - Studies of the sites of intracellular degradation of apolipoprotein B in Hep G2 cells. AB - We previously reported that treatment of Hep G2 cells with oleate significantly increased apolipoprotein B (apoB) secretion by reducing early intracellular degradation of nascent apoB. In the current study, inhibitors of secretory protein transport (brefeldin A and monensin), cell fractionation studies, and protease protection assays were utilized to determine the location of apoB degradation and to better define the mechanism whereby oleate treatment reduces nascent apoB intracellular degradation. When cells were treated with brefeldin A, which blocks endoplasmic reticulum (ER) to Golgi protein transport, apoB degradation continued in control cells, suggesting that apoB is degraded in the ER. When oleate-treated cells were blocked with brefeldin A, oleate failed to protect apoB from intracellular degradation. The effects of brefeldin A were not due to effects on lipid synthesis as brefeldin A did not inhibit the synthesis of triglyceride, phospholipid, free cholesterol, or cholesteryl ester in control cells and did not prevent the increases in triglyceride (14-fold) and phospholipid (1.4-fold) synthesis seen in oleate-treated cells. Simultaneous treatment of cells with brefeldin A and nocodazole, which inhibits retrograde transport of proteins from Golgi to ER, added to the evidence for the ER as the site of apoB degradation. This conclusion received further support from experiments in which cells were treated with monensin, a Na+ ionophore which halts protein secretion at the level of the trans-Golgi network. Early degradation of nascent apoB (between 10 and 20 min of chase) was observed in monensin-treated cells, but then cellular apoB degradation ceased and apoB was stable during the remaining chase period. More apoB accumulated in the Golgi of cells that had been treated with oleate and monensin. These results suggest that ER degradation occurs in monensin-treated cells, but then stops as apoB is transferred to the Golgi. The results obtained in whole cells were confirmed in studies using isolated ER and Golgi, which indicated that ER contains a proteolytic activity which degrades apoB, in vitro, whereas Golgi does not. ApoB degradation in isolated ER was not reduced by pretreatment with oleate. Finally, protease protection assays carried out with isolated microsomes indicated that a majority of the apoB in both control or oleate-treated HepG2 cells was located on the cytosolic side of the membranes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1429612 TI - Crystallographic and biochemical studies of the (inactive) Lys-49 phospholipase A2 from the venom of Agkistridon piscivorus piscivorus. AB - Chemical, genetic, and structural studies have defined a critical role for Asp-49 in the calcium-mediated activation of extracellular phospholipases A2 (PLA2). In 1984, a new class of PLA2 was isolated in which this invariant aspartate was replaced with a lysine (Maragnore, J.M., Merutka, G., Cho, W., Welches, W., Kezdy, F.J., and Heinrikson, R.L. (1984) J. Biol. Chem. 259, 13839-13843; Maragnore, J.M., and Heinrikson, R.L. (1986) J. Biol. Chem. 261, 4797-4804). The enzymatic activity of Lys-49 PLA2s has been questioned based on biochemical, mutational, and structural studies (van den Bergh, C.J., Slotboom, A.J., Verheij, H.M., and de Haas, G.H. (1988) Eur. J. Biochem. 176, 353-357). In this paper, we describe the structures of two crystal forms of the Lys-49 PLA2 isolated from the venom of Agkistridon piscivorus piscivorus. The refined models, along with complementary biochemical analysis, clarify the structural basis for the enzymatic inactivity of Lys-49 proteins. PMID- 1429613 TI - A simple, rapid method for purification of epsilon-subunit, coupling factor 6, subunit d, and subunit e from rat liver H(+)-ATP synthase and determination of the complete amino acid sequence of epsilon-subunit. AB - The rat liver mitochondrial epsilon-subunit, coupling factor 6, subunit d, and subunit e of H(+)-ATP synthase, which are all extra subunits with no counterparts in Escherichia coli, were purified by reverse-phase high performance liquid chromatography. The complete amino acid sequence of the rat epsilon-subunit was determined by automated Edman degradation of the whole protein and derived peptides. The protein contains 50 amino acids and has a molecular mass of 5635 kDa. It is a basic hydrophilic protein with an isoelectric point of 10.5. The sequence of the rat epsilon-subunit is highly homologous with that of the epsilon subunit of bovine heart and slightly similar to those of the epsilon-subunit of the yeast and sweet potato mitochondria. However, it has no homology with any subunit of bacterial or chloroplast H(+)-ATP synthase. PMID- 1429614 TI - Structural characterization of free glycolipids which are potential precursors for glycophosphatidylinositol anchors in mouse thymoma cell lines. AB - Biosynthesis of glycophosphatidylinositol-anchored membrane glycoproteins proceeds through the attachment of a preformed glycolipid onto a C-terminal amino acid rapidly after translation. Here we describe the structural analysis of two very polar glycolipids which can be observed after metabolic labeling of lymphoma cell lines S1A and EL-4 with either tritiated myo-inositol, mannose, or ethanolamine. These lipids are not made by mutant cells deficient in the biosynthesis of glycophosphatidylinositol anchors. The lipids were isolated, and their carbohydrate moiety was characterized using hydrofluoric acid dephosphorylation, nitrous acid deamination, acetolysis, exoglycosidase treatments, and combinations thereof to produce labeled fragments which could be analyzed by paper chromatography. Results are compatible with the structure (X- >)Man alpha 1,2 Man alpha 1,6(Y-->)Man alpha-GlcN-acylinositol, X and Y being hydrofluoric acid-sensitive substituents (most likely phosphoethanolamine). The anchor oligosaccharide of the glycophosphatidylinositol protein anchors of S1A cells was isolated, similarly characterized, and found to contain the identical carbohydrate structure. Pulse-chase experiments indicate that the very polar glycolipids have half-lives which are much longer than the one of phosphatidylinositol. The results suggest that these very polar glycolipids represent supernumerary precursor glycolipids which did not get transferred onto proteins or represent processed forms of such precursors. PMID- 1429615 TI - Glutamate dehydrogenase from the hyperthermophile Pyrococcus furiosus. Thermal denaturation and activation. AB - Pyrococcus furiosus is a marine hyperthermophile that grows optimally at 100 degrees C. Glutamate dehydrogenase (GDH) from P. furiosus is a hexamer of identical subunits and has an M(r) = 270,000 +/- 5500 at 25 degrees C. Electron micrographs showed that the subunit arrangement is similar to that of GDH from bovine liver (i.e. 3/2 symmetry in the form of a triangular antiprism). However, GDH from P. furiosus is inactive at temperatures below 40 degrees C and undergoes heat activation above 40 degrees C. Both NAD+ and NADP+ are utilized as cofactors. Apparently the inactive enzyme also binds cofactors, since the enzyme maintains the ability to bind to an affinity column (Cibacron blue F3GA) and is specifically eluted with NADP+. Conformational changes that accompany activation and thermal denaturation were detected by precision differential scanning microcalorimetry. Thermal denaturation starts at 110 degrees C and is completed at 118 degrees C. delta(cal) = 414 Kcal [mol GDH]-1. Tm = 113 degrees C. This increase in heat capacity indicates an extensive irreversible unfolding of the secondary structure as evidenced also by a sharp increase in absorbance at 280 nm and inactivation of the enzyme. The process of heat activation of GDH from 40 to 80 degrees C is accompanied by a much smaller increase in absorbance at 280 nm and a reversible increase in heat capacity with delta(cal) = 187 Kcal [mol GDH]-1 and Tm = 57 degrees C. This absorbance change as well as the moderate increase in heat capacity suggest that thermal activation leads to some exposure of hydrophobic groups to solvent water as the GDH structure is opened slightly. The increase in absorbance at 280 nm during activation is only 12% of that for denaturation. Overall, GDH appears to be well adapted to correspond with the growth response of P. furiosus to temperature. PMID- 1429616 TI - Isoprenoid requirement for intracellular transport and processing of murine leukemia virus envelope protein. AB - Lovastatin blocks the biosynthesis of the isoprenoid precursor, mevalonate. When Friend murine erythroleukemia (MEL) cells are cultured in medium containing lovastatin, the precursor of murine leukemia virus envelope glycoprotein (gPr90env) fails to undergo proteolytic processing, which normally occurs in the Golgi complex. Consequently, newly synthesized envelope proteins are not incorporated into viral particles that are shed into the culture medium. gPr90env appears to be localized in a pre-Golgi membrane compartment, based on its enrichment in subcellular fractions containing NADPH-cytochrome c reductase activity and the sensitivity of its carbohydrate chains to digestion with endoglycosidase H. Arrest of gPr90env processing occurs at concentrations of lovastatin that are not cytostatic, and the effect of the inhibitor is prevented by addition of mevalonate to the medium. The low molecular mass GTP-binding proteins, rab1p and rab6p, which are believed to function in early steps of the exocytic pathway, are normally modified posttranslationally by geranylgeranyl isoprenoids. However, in MEL cells treated with 1 microM lovastatin, nonisoprenylated forms of these proteins accumulate in the cytosol prior to arrest of gPr90env processing. These observations suggest that lovastatin may prevent viral envelope precursors from reaching the Golgi compartment by blocking the isoprenylation of rab proteins required for ER to Golgi transport. PMID- 1429617 TI - rab15, a novel low molecular weight GTP-binding protein specifically expressed in rat brain. PMID- 1429618 TI - The gene for stinging nettle lectin (Urtica dioica agglutinin) encodes both a lectin and a chitinase. PMID- 1429619 TI - Expression of 7 alpha-hydroxylase in non-hepatic cells results in liver phenotypic resistance of the low density lipoprotein receptor to cholesterol repression. AB - The goal of this study was to understand why the expression of low density lipoprotein (LDL) receptors by the liver is poorly down-regulated by cholesterol. We examined the hypothesis that 7 alpha-hydroxylase may indirectly induce the expression of the LDL receptor by metabolizing, i.e. inactivating oxysterol repressors. Non-hepatic Chinese hamster ovary cells, transfected with a plasmid encoding 7 alpha-hydroxylase, expressed both the mRNA and functional activity of this liver-specific enzyme. In the presence of 5% serum, expression of the LDL receptor by transfected cells was > 20 times that of non-transfected cells despite a 50% increased content of cholesterol ester. Both cell types displayed an almost complete repression of the LDL receptor by the oxysterol 25 hydroxycholesterol, suggesting that transcriptional control of the LDL receptor gene remained intact in the transfected cells. However, only cells expressing 7 alpha-hydroxylase showed a derepression of the LDL receptor with time. This transient sensitivity to 25-hydroxycholesterol repression was attributed to a 3 fold greater rate of metabolism of [3H]25-hydroxycholesterol. The paradoxical induction of LDL receptor mRNA in transfected cells having greater amounts of cholesterol esters suggests that 7 alpha-hydroxylase may preferentially use oxysterols rather than cholesterol as substrates. The combined data are consistent with the proposal that 7 alpha-hydroxylase indirectly induces the LDL receptor gene by metabolizing (inactivating) oxysterol repressors. Liver-specific expression of 7 alpha-hydroxylase can account for the relative resistance of hepatic LDL receptors to down-regulation. PMID- 1429621 TI - Tripartite functional assembly of a large class I aminoacyl tRNA synthetase. AB - A 939-amino acid monomeric class I tRNA synthetase has been split into three inactive peptides. The three peptides spontaneously assemble in vivo to reconstitute active protein. Active tripartite complexes were demonstrated in vitro. The tripartite assembly of this synthetase increases by several-fold the size of a polypeptide that has been demonstrated to be assembled from more than two constituent pieces. The results indicate that contemporary single-chain tRNA synthetases or other large proteins could in principle develop from intermediates composed of non-covalent assemblages of multiple peptides. PMID- 1429620 TI - Subunit 4 of the 26 S protease is a member of a novel eukaryotic ATPase family. AB - Ubiquitinated proteins are degraded by a 26 S ATP-dependent protease. SDS polyacrylamide gel electrophoresis analysis of the purified 26 S enzyme reveals more than 20 polypeptides ranging in apparent molecular masses from 20 to 110 kDa. Although many of the subunits smaller than 30 kDa are members of the multicatalytic protease family, the identity and function of the larger polypeptides have remained unknown. We report here the cDNA sequence for subunit 4, a 51-kDa chain of the 26 S protease. Subunit 4 belongs to a recently identified eukaryotic ATPase family, which includes proteins involved in peroxisome formation, secretion, and human immunodeficiency virus gene expression. Subunit 4 also shows weak similarity to ClpA, the ATP-binding subunit of the Escherichia coli protease, Clp. PMID- 1429622 TI - The amino terminus of nerve growth factor is involved in the interaction with the receptor tyrosine kinase p140trkA. AB - The amino terminus of nerve growth factor (NGF) is susceptible to proteolytic cleavage. A comparison of the bioactivity of highly purified full-length recombinant human (1-118)rhNGF and NH2-terminal truncated (10-118)rhNGF revealed lower potency of (10-118)rhNGF with regard to early NGF responses in neuron-like PC12 cells. Approximately 50 times higher concentrations of (10-118)rhNGF than (1 118)rhNGF were required to elicit the same extent of tyrosine phosphorylation of key enzymes in different second messenger pathways, i.e. the NGF receptor tyrosine kinase p140trkA, phospholipase C gamma-1, and the extracellular signal regulated kinase ERK1. A similar reduced potency for induction of the transcription factor c-Fos was observed with (10-118)rhNGF compared to (1 118)rhNGF. The lower potency of (10-118)rhNGF in triggering early responses correlated with its 40-fold lower affinity for PC12 cells. Whereas (10-118)rhNGF had a more than 300-fold lower affinity for the high affinity receptor p140trkA than (1-118)rhNGF, amino-terminal truncation of NGF changed its affinity for the low affinity receptor p75NGFR only slightly (5-10-fold). These observations suggest that amino acids 1-9 of NGF are important for binding to the signal transducing receptor p140trkA. Proteolytic cleavage of the NGF amino terminus, therefore, reduces its potency in starting several second messenger pathways leading to neuronal differentiation of PC12 cells. PMID- 1429623 TI - Preferential cleavage of des-31,32-proinsulin over intact proinsulin by the insulin secretory granule type II endopeptidase. Implication of a favored route for prohormone processing. AB - Two Ca(2+)-dependent endopeptidase activities are involved in proinsulin to insulin conversion: type I cleaves COOH-terminal to proinsulin Arg31-Arg32 (B chain/C-peptide junction); and type II preferentially cleaves at the Lys64-Arg65 site (C-peptide/A-chain junction). To further understand the mechanism of proinsulin processing, we have investigated types I and II endopeptidase processing of intact proinsulin in parallel to that of the conversion intermediates, des-31,32-proinsulin and des-64,65-proinsulin. The type I processed des-64,65-proinsulin and proinsulin at the same rate. In contrast, the type II endopeptidase processed des-31,32-proinsulin at a much faster rate (> 19 fold; p < 0.001) than it did intact proinsulin. Furthermore, unlabeled proinsulin concentrations required for competitive inhibition of 125I-labeled des-64,65 proinsulin and 125I-proinsulin processing by a purified insulin secretory granule lysate were similar (ID50 = 14-16 microM), whereas inhibition of 125I-labeled des 31,32-proinsulin processing required a higher nonradiolabeled proinsulin concentration (ID50 = 197 microM). Synthetic peptides corresponding to the sequences surrounding Lys64-Arg65 (AC-peptide/substrate) and Arg31-Arg32 (BC peptide/substrate) of human proinsulin were synthesized for use as specific substrates or competitive inhibitors. Cleavage of the BC-substrate by type I and AC-substrate by type II was COOH-terminal of the dibasic sequence, with similar Ca(2+)-and pH requirements previously observed for proinsulin cleavage. Apparent Km and Vmax for type I processing of the BC-substrate was Km = 20 microM; Vmax = 22.8 pmol/min, and for type II processing of the AC-substrate was Km = 68 microM; Vmax = 97 pmol/min. In competitive inhibition assays, the BC-peptide similarly blocked insulin secretory granule lysate processing of des-64,65-proinsulin and proinsulin (ID50 = 45-55 microM), but did not inhibit des-31,32-proinsulin processing. However, the AC-peptide preferentially inhibited insulin secretory granule lysate processing of des-31,32-proinsulin (ID50 = microM) compared to proinsulin (ID50 = 330 microM), and not des-64,65-proinsulin. We conclude that the type I endopeptidase recognized des-64,65-proinsulin and proinsulin as similar substrates, whereas the type II endopeptidase has a stronger preference for des-31,32-proinsulin compared to intact proinsulin. Furthermore, we suggest that in intact proinsulin there exists a constraint to efficient processing that is relieved following type I processing. Structural flexibility, in addition to the presence of Lys64-Arg65, therefore appears to be important for type II endopeptidase specificity and may provide a molecular basis for a preferential route of proinsulin conversion via des-31,32-proinsulin. PMID- 1429624 TI - Interaction between the Saccharomyces cerevisiae CDC25 gene product and mammalian ras. AB - In order to characterize the interaction between the Saccharomyces cerevisiae Cdc25 protein and Harvey-ras (p21H-ras), we have constructed a yeast strain disrupted at the RAS1 and RAS2 loci, expressing both p21H-ras and the catalytic domain of the bovine GTPase activating protein (GAP) and containing the cdc25-2 mutation. Such a strain exhibits a temperature-sensitive phenotype. The shift to the nonpermissive temperature is accompanied by the loss of guanyl nucleotide dependent activity of adenylylcyclase in vitro. The temperature-sensitive phenotype can be rescued by CDC25 itself, as well as by a plasmid containing a truncated SDC25 gene. In addition, wild type CDC25 significantly improves the guanyl nucleotide response observed in the background of the cdc25ts allele at the permissive temperature in a dosage-dependent manner and restores the guanyl nucleotide response at the restrictive temperature. Both CDC25 and a truncated SDC25 also restored p21H-ras-dependent guanyl nucleotide response in a strain isogenic to the one described above but containing a disrupted CDC25 locus instead of the temperature-sensitive allele. These results suggest that the S. cerevisiae Cdc25 protein interacts with p21H-ras expressed in yeast by promoting GDP-GTP exchange. It follows that the yeast system can be used for characterizing the interaction between guanyl nucleotide exchangers of Ras proteins and mammalian p21H-ras. PMID- 1429625 TI - Identification of an essential region for growth signal transduction in the cytoplasmic domain of the human interleukin-4 receptor. AB - Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system by regulating proliferation and differentiation of a wide variety of lymphoid and myeloid cells. These biological effects are manifested via binding of IL-4 to specific membrane-associated high affinity receptors. While the IL-4 receptor (IL-4R) cDNA expresses high affinity binding sites when transfected in COS7 cells, its intracellular domain lacks consensus motifs for known signal transducing molecules such as a tyrosine kinase. In this study, we use a DNA deletion approach to explore the mechanism of signal transduction utilized by the human IL-4R cDNA expressed in a murine pro-B cell line, Ba/F3 cells. Using this system, we have identified the critical region of the cytoplasmic domain of human IL-4R for human IL-4-induced transduction of a growth signal in these cells. Our data indicate that the critical region for signal transduction is located between amino acid residues 433-473 numbering from the carboxyl terminus. This region is highly conserved between mouse and human IL-4R but lacks homology with other cytokine receptors. Our studies additionally demonstrate that the cytoplasmic domain is not essential for forming high affinity IL-4-binding sites nor for ligand internalization. PMID- 1429626 TI - The crystal structures at 2.2-A resolution of hydroxyethylene-based inhibitors bound to human immunodeficiency virus type 1 protease show that the inhibitors are present in two distinct orientations. AB - As part of a structure-based drug design program directed against enzyme targets in the human immunodeficiency virus (HIV), we have determined the three dimensional structures of the HIV type 1 protease complexed with two hydroxyethylene-based inhibitors. The inhibitors (SKF 107457 and SKF 108738) are hexapeptide substrate analogues with the scissile bond being replaced by a hydroxyethylene isostere. The structures were determined using x-ray diffraction data to 2.2 A measured at the Cornell High Energy Synchrotron Source on hexagonal crystals of each of the complexes. The structures have been extensively refined using a reciprocal space least-squares method to conventional crystallographic R factors of 0.186 and 0.159, respectively. The protein structure differs from that in the unliganded state of the enzyme and is most similar to that of the structure of the other reported (Jaskolski, M., Tomasselli, A. G., Sawyer, T. K., Staples, D. G., Heinrikson, R. L., Schneider, J., Kent, S. B. H., and Wlodawer, A. (1990) Biochemistry 29, 5889-5907) hydroxyethylene-based inhibitor complex. Unlike in that structure, however, the inhibitors are observed, in the present crystal structures, in two equally abundant orientations that are a consequence of the homodimeric nature of the enzyme coupled with the asymmetric structures of the inhibitors. Although the differences between the two inhibitors used in the present study are confined to the P1' site, the van der Waals interactions made by the inhibitor atoms with the amino acid residues in the protein differ throughout the structures of the inhibitors. PMID- 1429627 TI - The organization and expression of essential transcription translation component genes in the extremely thermophilic eubacterium Thermotoga maritima. AB - A 5789-nucleotide-long EcoRI fragment from the genome of Thermotoga maritima, identified by cross-hybridization to L11, L1, L10, and L12 ribosomal protein gene sequences from Escherichia coli, was cloned and sequenced. The fragment encodes five tRNAs (tRNA(met1), anticodon complementary to AUG; tRNA(met2), AUG; tRNA(thr), ACA; tRNA(tyr), UAC; tRNA(trp), UGG), the transcription termination antitermination factor nusG, the four 50 S subunit ribosomal proteins L11, L1, L10, and L12, and the amino-terminal portion of the RNA polymerase beta subunit protein. The five tRNA genes, the nusG gene, and the L11, L1, L10, and L12 ribosomal protein genes form a complex transcription unit. Transcripts appear to be initiated from an upstream promoter, P1, located in front of the tRNA(met1) gene and from three internal promoters: P2 is located immediately in front of the tRNA(met2) gene; PL10 is near the beginning of the L1-L10 intergenic space, and PL12 is at the end of the L10 gene sequence. The tRNA sequences are excised from the leader regions of the P1- and P2-initiated transcripts. Three putative but potentially important regulatory sequences were identified within this operon: an L1 translational control site, a transcription attenuator, and a strong rho independent terminator. The strong terminator located distal to the L12 gene overlaps a fifth promoter, P beta, which is used to initiate transcripts of the downstream RNA polymerase beta subunit gene. The T. maritima NusG protein exhibits 43% amino acid sequence identity when aligned to the E. coli protein; the alignment is interrupted by a large 171-amino acid-long insertion into the T. maritima protein after codon 45. PMID- 1429628 TI - Appendix. Sequence of the beta-subunit of oxaloacetate decarboxylase from Klebsiella pneumoniae: a correction of the C-terminal part. PMID- 1429629 TI - Maltose chemotaxis involves residues in the N-terminal and C-terminal domains on the same face of maltose-binding protein. AB - The periplasmic maltose-binding protein (MBP) of Escherichia coli is the recognition component of the maltose chemoreceptor and of the active transport system for maltose. It interacts with the Tar chemotactic signal transducer and the integral cytoplasmic-membrane components (the MalF and MalG proteins) of the maltose transport system. Maltose binds in a cleft between the globular N terminal and C-terminal domains of MBP, which are connected by a moveable hinge. The two domains undergo a large motion relative to one another as the protein moves from the open, unbound state to the closed, ligand-bound state. We generated, by doped-primer mutagenesis, amino acid substitutions that specifically disrupt the chemotactic function of MBP. These substitutions cluster in two well-defined regions that are nearly contiguous on the surface of MBP in its closed conformation. One region is in the N-terminal domain and one is in the C-terminal domain. The distance between the two regions is expected to change substantially as the protein goes from the open to the closed form. These results support a model in which ligand binding brings two recognition sites on MBP into the proper spatial relationship to interact with complementary sites on Tar. Mutations in MBP that appear to cause defects in interaction with MalF and MalG are distributed differently from mutations that primarily affect maltose taxis. We conclude that the regions of MBP that contact Tar and those that contact MalF and MalG are adjacent on the face of the protein opposite the hinge connecting the two domains and that those regions are largely, although perhaps not entirely, distinct. PMID- 1429630 TI - Fluoroaluminate complexes are bifunctional analogues of phosphate in sarcoplasmic reticulum Ca(2+)-ATPase. AB - The mechanism of inhibition of the sarcoplamc reticulum (SR) Ca(2+)-ATPase by the fluoroaluminate complexes was investigated. First, AlF4- was shown to bind to the Ca(2+)-free conformation of the enzyme by a slow quasi-irreversible process. The rate constants of the reaction are k+ = 16 x 10(3) M-1 s-1 and k- < 1.5 10(-3) s 1. We directly measured a stoichiometry of about 4.8 nmol of AlF4- bound/mg of protein. Mg2+ was a necessary cofactor for the reaction with a dissociation constant of 3 mM. It was demonstrated (Dupont, Y., and Pougeois, R. (1983) FEBS Lett. 156, 93-98) that phosphorylation by P(i) induced a dehydration of the catalytic site. The same process has been shown here to occur upon AlF4- binding either by the use of Me2SO or by demonstration of an increase of bound 2',3'-O (2,4,6-trinitrocyclohexadienyldene)adenosine triphosphate fluorescence. Phosphorylation by P(i) is inhibited by the binding of AlF4-. Second, a fluoroaluminate complex, presumably AlF4-, was also shown to bind to the Ca(2+) bound conformation of the Ca(2+)-ATPase in the presence of ADP and stabilize a E1.Ca2.ADP.AlFx complex. The dissociation constant of the nucleotidic site for ADP was shifted to the micromolar range. The Ca2+ ions bound on the external high affinity sites became occluded upon binding of (ADP + AlFx). We propose that AlF4 mimics P(i) binding to the Ca(2+)-free conformation of the ATPase and stabilizes an intermediate similar to the acyl-phosphate derivative; it also acts as an analogue of the gamma-phosphate of ATP and stabilizes an E1.[Ca2].ADP.AlF4 complex where the Ca2+ ions are occluded. PMID- 1429631 TI - Overexpression, site-directed mutagenesis, and mechanism of Escherichia coli acid phosphatase. AB - Site-directed mutagenesis was used to examine the catalytic importance of 2 histidine and 4 arginine residues in Escherichia coli periplasmic acid phosphatase (EcAP). The residues that were selected as targets for mutagenesis were those that were also conserved in a number of high molecular weight acid phosphatases from eukaryotic organisms, including human prostatic and lysosomal acid phosphatases. Both wild type EcAP and mutant proteins were overproduced in E. coli using an expression system based on the T7 RNA polymerase promoter, and the proteins were purified to homogeneity. Examination of the purified mutant proteins by circular dichroism and proton NMR spectroscopy revealed no significant conformational changes. The replacement of Arg16 and His17 residues that were localized in a conserved N-terminal RHGXRXP motif resulted in the complete elimination of EcAP enzymatic activity. Critical roles for Arg20, Arg92, and His303 were also established because the corresponding mutant proteins exhibited residual activities that were not higher than 0.4% of that of wild type enzyme. In contrast, the replacement of Arg63 did not cause a significant alteration of the kinetic parameters. The results are in agreement with a previously postulated distant relationship between acid phosphatases, phosphoglycerate mutases, and fructose-2,6-bisphosphatase. These and earlier results are also consistent with the conclusion that 2 histidine residues participate in the catalytic mechanism of acid phosphatases, with His17 playing the role of a nucleophilic acceptor of the phospho group, whereas His303 may act as a proton donor to the alcohol or phenol. PMID- 1429632 TI - Nonproteolytic "activation" of prorenin by active site-directed renin inhibitors as demonstrated by renin-specific monoclonal antibody. AB - Incubation of human plasma prorenin (PR), the enzymatically inactive precursor of renin (EC 3.4.23.15), with a number of nonpeptide high-affinity active site directed renin inhibitors induces a conformational change in PR, which was detected by a monoclonal antibody that reacts with active renin but not with native inactive PR. This conformational change also occurred when inactive PR was activated during exposure to low pH. Nonproteolytically acid-activated PR, and inhibitor-"activated" PR, as well as native PR, were retained on a blue Sepharose column, in contrast to proteolytically activated PR. Kinetic analysis of the activation of plasma prorenin by renin inhibitor (INH) indicated that native plasma contains an open intermediary form of prorenin, PRoi, in which the active site is exposed and which is in rapid equilibrium with the inactive closed form, PRc. PRoi reacts with inhibitor to form a reversible complex, PRoi.INH, which undergoes a conformational change resulting in a tight complex of a modified open form of prorenin, PRo, and the inhibitor, PRoi.INH-->PRo.INH. The PRoi-to-PRo conversion leads to the expression of an epitope on the renin part of the molecule that is recognized by a renin-specific monoclonal antibody. Presumably, PRo corresponds to the enzymatically active form of PR that is formed during exposure to low pH. Thus, it seems that the propeptide of PR interacts with the renin part of the molecule not only at or near the enzyme's active site but also at some distance from the active site. Interference with the first interaction by renin inhibitor leads to destabilization of the propeptide, by which the second interaction is disrupted and the enzyme assumes its active conformation. The results of this study may provide a model for substrate-mediated prorenin activation and increase the likelihood that enzymatically active prorenin is formed in vivo. PMID- 1429633 TI - Coordination structure of the ferric heme iron in engineered distal histidine myoglobin mutants. AB - Recombinant human myoglobin mutants with the distal His residue (E7, His64) replaced by Leu, Val, or Gln residues were prepared by site-directed mutagenesis and expression in Escherichia coli. Electronic and coordination structures of the ferric heme iron in the recombinant myoglobin proteins were examined by optical absorption, EPR, 1H NMR, magnetic circular dichroism, and x-ray spectroscopy. Mutations, His-->Val and His-->Leu, remove the heme-bound water molecule resulting in a five-coordinate heme iron at neutral pH, while the heme-bound water molecule appears to be retained in the engineered myoglobin with His-->Gln substitution as in the wild-type protein. The distal Val and distal Leu ferric myoglobin mutants at neutral pH exhibited EPR spectra with g perpendicular values smaller than 6, which could be interpreted as an admixture of intermediate (S = 3/2) and high (S = 5/2) spin states. At alkaline pH, the distal Gln mutant is in the same so-called "hydroxy low spin" form as the wild-type protein, while the distal Leu and distal Val mutants are in high spin states. The ligand binding properties of these recombinant myoglobin proteins were studied by measurements of azide equilibrium and cyanide binding. The distal Leu and distal Val mutants exhibited diminished azide affinity and extremely slow cyanide binding, while the distal Gln mutant showed azide affinity and cyanide association rate constants similar to those of the wild-type protein. PMID- 1429634 TI - The identification and characterization of a GDP-dissociation inhibitor (GDI) for the CDC42Hs protein. AB - The ras-related protein, CDC42Hs, is a 22-kDa GTP-binding protein which is the human homolog of a Saccharomyces cerevisiae yeast-cell-division cycle protein. In attempting to isolate and biochemically characterize mammalian proteins capable of regulating various activities of CDC42Hs, we have identified an activity in bovine brain cytosol which effectively inhibits the dissociation of [3H]GDP from the platelet- or the Spodoptera frugiperda-expressed CDC42Hs protein. The purification of this activity was achieved by a series of steps which included ammonium sulfate fractionation, DEAE-Sephacel, Mono-Q, and Mono-S chromatographies. The purified CDC42Hs regulatory protein has an apparent molecular weight of 28,000, and cyanogen bromide-generated peptide sequences of this protein were identical to sequences from the carboxyl-terminal portion of rho-GDP-dissociation inhibitor (rho-GDI) (Fukumoto, Y., Kaibuchi, K., Hori, Y., Fujioka, H., Araki, S., Ueda, T., Kikuchi, A., and Takai, Y. (1990) Oncogene 5, 1321-1328). In addition, an Escherichia coli-expressed, glutathione S-transferase rho-GDI fusion protein fully substitutes for the GDI which we have purified from bovine brain in its ability to inhibit GDP dissociation from CDC42Hs. These findings suggest either that a common regulatory protein (GDI) is capable of inhibiting GDP dissociation from the rho and CDC42Hs proteins or that these two GTP-binding proteins interact with GDI proteins of very similar structure. The purified brain GDI protein shows little ability to inhibit GDP dissociation from the E. coli-expressed CDC42Hs and is capable of only a very weak inhibition of the dissociation of [35S]guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) from the Spodoptera frugiperda-expressed CDC42. However, brain GDI very effectively inhibits the ability of the human dbl oncogene product to catalyze GDP dissociation from CDC42Hs. In addition to influencing guanine nucleotide association with CDC42Hs, the purified brain GDI protein also appears to catalyze the dissociation of CDC42Hs from the plasma membranes of human placenta and human epidermoid carcinoma (A431) cells. This effect by the GDI protein is observed whether the membrane-associated CDC42Hs is preincubated with GDP, GTP gamma S, or no guanine nucleotides, and occurs over a similar concentration range as that necessary for the inhibition of the intrinsic GDP dissociation. PMID- 1429635 TI - Identification by site-directed mutagenesis of two lysine residues in cholesterol side chain cleavage cytochrome P450 that are essential for adrenodoxin binding. AB - Utilizing site-directed mutagenesis and an Escherichia coli expression system for bovine cholesterol side chain cleavage cytochrome P450, lysine residues at 377 and 381 are found to play crucial roles in binding bovine adrenodoxin, required for transfer of electrons to mitochondrial P450s. These lysine residues are conserved among mitochondrial P450s and have been implicated previously by chemical modification studies as being important for adrenodoxin binding. In the present study, site-directed mutagenesis producing either neutral or positive amino acids at 377 or 381 has no effect on the structure of side chain cleavage cytochrome P450 as determined spectrally or on the enzymatic conversion of cholesterol to pregnenolone. However, the estimated Ks of adrenodoxin binding is increased approximately 150-600-fold depending on the particular mutation. Therefore these conserved positively charged residues in mitochondrial P450s are the key sites for adrenodoxin binding which is electrostatic in nature. PMID- 1429636 TI - Activation of the acetyl-coenzyme A:lysoplatelet-activating factor acetyltransferase regulates platelet-activating factor synthesis in human endothelial cells. AB - Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF) is a phospholipid with many physiological actions. It is synthesized by endothelial cells and a variety of others in response to stimulation with receptor-mediated agonists. In endothelial cells it remains associated with the surface of the cell and serves as a signal for adhesive interactions with leukocytes. Thus, its synthesis must be precisely regulated. In previous work we have shown that PAF synthesis is regulated at the initiating step, a phospholipase A2. Here we demonstrate that the subsequent step of PAF synthesis, the acetyl-CoA:lyso-PAF acetyltransferase, is rapidly activated when cells are exposed to thrombin or other agonists. We found that the activity increased from basal values (5 nmol/mg/min) to approximately 3-fold higher within 1 min following the addition of agonists. The enzyme activity returned to basal levels within 10 min. The pattern of activation and inactivation suggested covalent modification of the enzyme. This was supported in experiments in which we showed that homogenates had stable enhanced activity and that there was no evidence for an activator or inhibitor. Pretreatment of the cells with vanadate, an inhibitor of protein phosphatases, markedly prolonged the activation state. In subsequent studies we pretreated intact cells with vanadate to block inactivation of the enzyme and then measured the accumulation of PAF in response to thrombin. We found that it was markedly augmented and prolonged. From this we conclude that the synthesis of PAF in intact cells is regulated by the activity of the acetyltransferase. We characterized requirements for activation of acetyltransferase and found that it was not dependent on the influx of intracellular calcium but that calcium entry did influence the length of time for which the enzyme was activated. The acetyltransferase in endothelial cells was shown to be a specific enzyme that did not catalyze the transfer of long chain acyl groups from acyl-CoA to lysophospholipids and demonstrated modest specificity for the acceptor lysophospholipids. These results suggest that activation of the acetyltransferase is a crucial determinant of the amount of PAF synthesized in activated endothelial cells. PMID- 1429637 TI - Autophosphorylation of protein kinase C may require a high order of protein phospholipid aggregates. AB - The activation of protein kinase C (PKC) usually displays cofactor requirements that include phosphatidylserine (PS), diacylglycerol, and calcium. A complicating factor is that good exogenous substrates of PKC are polycationic proteins or peptides that form aggregates with PS in the assay. This study examined the autophosphorylation of PKC using assays with phospholipid provided in the form of vesicles or phospholipid-Triton mixed micelles. The results showed a close correlation between PKC autophosphorylation and the formation of aggregated assay components. Aggregation occurred primarily by the action of Mg2+ on phospholipids and appeared to underlie a number of major features of PKC autophosphorylation. For example, autophosphorylation required higher concentrations of PS than phosphorylation of exogenous substrates. This appeared to be the result of the different PS requirements of aggregation by divalent metal ions and cationic substrates. An unanticipated result was that aggregation of mixed micelles showed specificity for PS, high cooperativity with respect to several agents, and a requirement for calcium. These parameters were remarkably similar to those describing PKC autophosphorylation. Several major implications are evident in this study. Since the autophosphorylation assay is not a well defined system of monodisperse materials, autophosphorylation of PKC may proceed by intra- or interpeptide mechanism. The uniform correlation between aggregation and production of PKC activity suggested that kinetic parameters may represent interactions of assay components other than the enzyme. Aggregation, which appeared necessary for in vitro activation of PKC, may represent the expression of important but undefined in vivo requirements for this enzyme's function. PMID- 1429638 TI - Identification of critical amino-terminal regions of XylS. The positive regulator encoded by the TOL plasmid. AB - The XylS protein is the positive regulator of the promoter controlling the meta cleavage pathway (Pm) for catabolism of certain alkylbenzoates on the TOL plasmid of Pseudomonas. Transcription from Pm is mediated by XylS either in the presence of benzoate effectors or through XylS hyperproduction. Two regions of the NH2 terminus of XylS (residues 37-45) had been predicted to be involved in effector control of XylS transcriptional activation. Different methods were used to induce mutations in this region, including genetic selections (where Pm controlled a tetracycline resistance gene), bisulfite mutagenesis at a unique restriction site, and extensive oligonucleotide mutagenesis at residues 41 and 45. The mutants fell into four classes based on their phenotypes with respect to effector mediated activation of a Pm-lacZ fusion: (a) effector profiles similar to wild type, (b) no Pm stimulation with benzoates, (c) altered effector specificity, and (d) higher basal Pm activities, in some cases including changes in effector specificity. In some mutants, higher basal Pm activity was apparently due to mutations that increased XylS stability. Substitutions at Arg-41 resulted in all four mutant phenotypes, indicating that this is a critical residue in XylS for effector stimulation of transcription activity. PMID- 1429639 TI - Human placental brush-border membrane Na(+)-pantothenate cotransport. AB - Membrane transport pathways for transplacental transfer of the water-soluble vitamin pantothenate were investigated by assessing the possible presence of a Na(+)-pantothenate cotransport mechanism in the maternal facing membrane of human placental epithelial cells. The presence of Na(+)-pantothenate cotransport was determined from radiolabeled tracer flux measurements of pantothenate uptake using preparations of purified brush-border membrane vesicles. Compared with other cations the imposition of an inward Na+ gradient stimulated vesicle uptake of pantothenate to levels approximately 40-fold greater than those observed at equilibrium. The observed stimulation of pantothenate uptake was not the result of indirect electrostatic coupling to an inside positive Na+ diffusion potential. In the absence of Na+ and pantothenate concentration gradients an inside negative voltage difference induced a Na(+)-dependent net influx of pantothenate, suggesting the presence of an electrogenic Na(+)-pantothenate cotransport mechanism. The effect of biotin on the kinetics of Na(+)-dependent pantothenate uptake and the effect of pantothenate on the kinetics of Na(+)-dependent biotin uptake suggested that placental absorption of biotin and pantothenate from the maternal circulation occurs by a common Na+ cotransport mechanism in apical brush border membrane. PMID- 1429640 TI - Energetics of lectin-carbohydrate binding. A microcalorimetric investigation of concanavalin A-oligomannoside complexation. AB - Despite years of study, a comprehensive picture of the binding of the lectin from Canavalia ensiformis, concanavalin A, to carbohydrates remains elusive. We report here studies on the interaction of concanavalin A with methyl 3,6-di-O-(alpha-D mannopyranosyl)-alpha-D-mannopyranoside, the minimum carbohydrate epitope that completely fills the oligosaccharide binding site, and the two conceptual disaccharide "halves" of the trisaccharide, methyl 3-O-(alpha-D-mannopyranosyl) alpha-D-mannopyranoside and methyl 6-O-(alpha-D-mannopyranosyl)-alpha-D mannopyranoside, using titration microcalorimetry. In all cases the interaction of protein and carbohydrate is enthalpically driven, with an unfavorable entropic contribution. The choice of concentration scales has an important impact on both the magnitude and, in some cases, the sign of the entropic component of the free energy of binding. The thermodynamic data suggest binding of the two disaccharides may take place in distinct sites, as opposed to binding in a single high affinity site. In contrast to carbohydrate-antibody binding, delta Cp values were small and negative, pointing to possible differences in the motifs used by the two groups of proteins to bind carbohydrates. The thermodynamic data are interpreted in terms of solvent reorganization. Cooperativity during lectin carbohydrate binding was also investigated. Significant cooperativity was observed only for binding of the trisaccharide, and gave a Hill plot coefficient of 1.3 for dimeric protein. PMID- 1429641 TI - The tricarboxylic acid cycle in Dictyostelium discoideum. I. Formulation of alternative kinetic representations. AB - Enzyme systems within living cells have recently been shown to be highly ordered structures that violate classic assumptions of the Michaelis-Menten formalism, which originally was developed for the characterization of isolated reactions in vitro. This evidence suggests that a thorough examination of alternative kinetic formalisms for integrated biochemical systems is in order. The purpose of this series of papers is to assess the utility of an alternative power-law formalism by carrying out a detailed comparative analysis of a relatively large, representative system--the tricarboxylic acid cycle of Dictyostelium discoideum. This system was chosen because considerable experimental information already has been synthesized into a detailed kinetic model of the intact system. In this first paper, we set the stage for subsequent analysis within the framework of the power-law formalism: we review the underlying theory, emphasizing recent developments, formulate the model in terms that are convenient for the analysis to follow, and develop the system representation in both the Michaelis-Menten and power-law forms. In the second paper (Shiraishi, F., and Savageau, M. A. (1992) J. Biol. Chem. 267, 22919-22925), these alternative representations are shown to be internally consistent and locally equivalent. The third paper (Shiraishi, F., and Savageau, M. A. (1992) J. Biol. Chem. 267, 22926-22933) provides a complete analysis of the steady state behavior and also treats the dynamic behavior of the model. PMID- 1429642 TI - The tricarboxylic acid cycle in Dictyostelium discoideum. II. Evaluation of model consistency and robustness. AB - When kinetic models of complex biochemical systems are reconstructed from knowledge of the component reactions that have been characterized in vitro, or when values must be assumed for some of the parameters, errors are invariably encountered, and, as a consequence, the resulting model is frequently internally inconsistent. The simplest and most basic manifestations of such logical inconsistency are the failure of the model to exhibit a steady state or to yield a steady state that is in agreement with the actual steady state of the integrated system, or to yield a steady state that is dynamically stable. Models that are consistent may nonetheless be lacking in robustness, which is manifested as a pathological sensitivity to small changes in the values of their parameters. In this paper, we examine the current model of the tricarboxylic acid cycle in Dictyostelium discoideum (see Shiraishi, F., and Savageau, M. A. (1992) J. Biol. Chem. 267, 22912-22918) with regard to these basic indicators of model quality. This may be viewed as a preliminary analysis; the object is to determine whether or not the model is reasonable and worthy of a more refined analysis and, if not, to diagnose the areas in need of modification before further analysis is undertaken. The results demonstrate that the current model of the tricarboxylic acid cycle is self-consistent and possesses a steady state that is in agreement with experimental evidence. However, the results also suggest that this model is not very robust. The high sensitivities of parameters influencing pyruvate metabolism indicate that the experimental characterization of these reactions might be fruitfully re-examined. These high sensitivities lead us to predict that this model of the tricarboxylic acid cycle should be accurate only over a very narrow range in variation of the independent variables. This is verified by the results presented in the following paper (Shiraishi, F., and Savageau, M. A. (1992) J. Biol. Chem. 267, 22926-22933). PMID- 1429643 TI - The tricarboxylic acid cycle in Dictyostelium discoideum. III. Analysis of steady state and dynamic behavior. AB - The examination of model robustness in the previous paper (Shiraishi, F., and Savageau, M. A. (1992) J. Biol. Chem. 267, 22919-22925 led to the suggestion that the current model for the tricarboxylic acid cycle in Dictyostelium discoideum is ill-determined with respect to one or more of the features reflecting pyruvate metabolism. This conclusion is further supported here by results of steady state and dynamic analyses. The tricarboxylic acid cycle, according to the current model, is poised on a knife's edge with its behavior rigidly determined; any alteration of the system's components leads to nonviable behavior, as exemplified by explosive accumulation of pyruvate and loss of steady state in response to a minute change in the level of malate dehydrogenase. With the additional results in this paper, we are able to refine the diagnosis of the problem and suggest three different areas of the current model that might profitably be re-examined by experiment. These include the kinetics of the reactions at the malate branch point, the turnover times for the alanine, glutamate, and aspartate pools in vivo, and the dynamic mass balances for the cofactor NAD. We also suggest a minimal modification in the current model that could alleviate or circumvent some of these problems. PMID- 1429644 TI - The tricarboxylic acid cycle in Dictyostelium discoideum. IV. Resolution of discrepancies between alternative methods of analysis. AB - Experimental studies of enzyme kinetics in vitro and metabolic fluxes in vivo have been used by Wright and her colleagues to develop a detailed kinetic model of the tricarboxylic acid cycle in Dictyostelium discoideum. This model has recently been been analyzed by two different methods (Albe, K. R., and Wright, B. E. (1992) J. Biol. Chem. 267, 3106-3114; Shiraishi, F., and Savageau, M. A. (1992) J. Biol. Chem. 267, 22926-22933 in an effort to determine the response of individual fluxes and metabolite concentrations to changes in levels of the enzymes that constitute the system. Individual responses were found to differ significantly in magnitude as well as in sign. Perhaps the most glaring difference concerns the influence of the enzyme succinate dehydrogenase on the flux through the cycle; in one study, it has the maximum influence, whereas, in the other, it has absolutely no influence. In this paper, we provide a resolution of these discrepancies. We have reconstructed the methodology of Albe and Wright and have been able to reproduce their results in detail. We show that their methodology does not yield a valid steady state analysis, and, consequently, that the conclusions drawn from their analysis must be called into question. First, they concluded that their model is realistic and predictive. It is now clear that their model is ill-determined and has a steady state only for unrealistically narrow conditions. Second, they concluded that their analysis is valid for variations of less than 2% in the levels of the enzymes because they could satisfy summation relationships considered to be mathematically inevitable. It is now clear that these relationships are neither necessary nor sufficient for establishing the validity of an analysis or the appropriateness of a biochemical model. Third, they concluded on the basis of their empirical methodology that certain enzymes are most important in influencing flux through the cycle. It is now clear that these results are inaccurate because of deficiencies in their methodology. Finally, they concluded that steady state analyses cannot be carried out experimentally because of the small variations required in enzyme levels. It is now clear that the requirement for such small variations reflects the ill determined character of the underlying model and is not a necessary property of the real system. PMID- 1429645 TI - Excitation energy transfer from phycocyanin to chlorophyll in an apcA-defective mutant of Synechocystis sp. PCC 6803. AB - A greenish mutant of the normally blue-green cyanobacterium Synechocystis sp. PCC 6803, designated UV6p, has been isolated and characterized. UV6p possesses functional photosystems I and II (PSI and PSII) but lacks normal light harvesting phycobilisomes because allophycocyanin is absent and core-specific linker proteins are almost entirely absent. The mutation responsible for the UV6p phenotype has been identified; it is a base substitution which results in the creation of a termination codon within the coding region of the apcA gene. Phycocyanin (PC) and phycobilisome rod linker proteins are present in UV6p and, despite the absence of core components, at least 35% of the PC is associated with rod linker proteins. At 77 K, light absorbed by PC of UV6p elicits PSI fluorescence comparable to that of wild type cells but produces greatly diminished PSII fluorescence. The results indicate that the assembly of rods is independent of cores and that light energy absorbed by rods can be transferred principally and directly to PSI. This energy transfer pathway, which may also be present in wild type, may have a regulatory role in maintaining the balance of input of excitation energy into PSI versus PSII during photosynthesis. PMID- 1429646 TI - Association of a receptor and G-protein-regulated phospholipase C with the cytoskeleton. AB - Approximately 98% of turkey erythrocyte phospholipase C (PLC) is cytosolic and is released by hypotonic lysis of the cells and extensive washing of the resultant erythrocyte ghosts. Well washed turkey erythrocyte ghosts retain a fraction of tightly associated PLC, which is activated by the P2y-purinergic receptor and G protein present in ghost membranes. The particulate PLC is sufficient to couple to all the available purinergic receptor-regulated G-protein. In contrast to ghosts, turkey erythrocyte plasma membrane preparations contain no detectable PLC. To investigate the subcellular location of the ghost-associated PLC, cytoskeletons were prepared by Triton X-100 extraction of turkey erythrocyte ghosts. The ghost-associated PLC was quantitatively recovered in cytoskeleton preparations. Cytoskeleton-associated PLC was solubilized by sodium cholate extraction, partially purified, and shown to reconstitute with PLC-free plasma membrane preparations in an agonist and guanine nucleotide-dependent fashion, indicating that the cytoskeleton-associated PLC is G-protein-regulated. Dissociation of erythrocyte ghost cytoskeletons with the actin-binding protein DNase 1 resulted in a dose-dependent inhibition of agonist and guanine nucleotide stimulated PLC responses in ghosts and caused release of PLC from ghost or cytoskeleton preparations. These data demonstrate the specific association of a receptor and G-protein-regulated PLC with a component of the detergent-insoluble cytoskeleton and indicate that the integrity of the actin cytoskeleton is important for localization and effective coupling of PLC to the relevant G protein. PMID- 1429647 TI - The effects of smooth muscle caldesmon on actin filament motility. AB - The movement of reconstituted thin filaments over an immobilized surface of thiophosphorylated smooth muscle myosin was examined using an in vitro motility assay. Reconstituted thin filaments contained actin, tropomyosin, and either purified chicken gizzard caldesmon or the purified COOH-terminal actin-binding fragment of caldesmon. Control actin-tropomyosin filaments moved at a velocity of 2.3 +/- 0.5 microns/s. Neither intact caldesmon nor the COOH-terminal fragment, when maintained in the monomeric form by treatment with 10 mM dithiothreitol, had any effect on filament velocity; and yet both were potent inhibitors of actin activated myosin ATPase activity, indicating that caldesmon primarily inhibits myosin binding as reported by Chalovich et al. (Chalovich, J. M., Hemric, M. E., and Velaz, L. (1990) Ann. N. Y. Acad. Sci. 599, 85-99). Inhibition of filament motion was, however, observed under conditions where cross-linking of caldesmon via disulfide bridges was present. To determine if monomeric caldesmon could "tether" actin filaments to the myosin surface by forming an actin-caldesmon myosin complex as suggested by Chalovich et al., we looked for caldesmon dependent filament binding and motility under conditions (80 mM KCl) where filament binding to myosin is weak and motility is not normally seen. At caldesmon concentrations > or = 0.26 microM, actin filament binding was increased and filament motion (2.6 +/- 0.6 microns/s) was observed. The enhanced motility seen with intact caldesmon was not observed with the addition of up to 26 microM COOH-terminal fragment. Moreover, a molar excess of the COOH-terminal fragment competitively reversed the enhanced binding seen with intact caldesmon. These results show that tethering of actin filaments to myosin by the formation of an actin-caldesmon-myosin complex enhanced productive acto-myosin interaction without placing a significant mechanical load on the moving filaments. PMID- 1429648 TI - Identification of cross-linking sites in bovine cartilage type IX collagen reveals an antiparallel type II-type IX molecular relationship and type IX to type IX bonding. AB - Type IX collagen functions in covalent cross-linkage to type II collagen in cartilage (Eyre, D. R., Apone, S., Wu, J. J., Ericsson, L. H., and Walsh, K. A. (1987) FEBS Lett. 220, 337-341). To understand this molecular relationship better, an analysis of all cross-linking sites labeled by [3H]borohydride was undertaken using the protein prepared from fetal bovine cartilage. Sequence analysis of tryptic peptides containing the 3H-labeled cross-links showed that each of the chains of type IX collagen, alpha 1(IX), alpha 2(IX), and alpha 3(IX), contained a site of cross-linking at the amino terminus of the COL2 triple helix to which the alpha 1(II)N-telopeptide could bond. The alpha 3(IX)COL2 domain alone also had an attachment site for the alpha 1(II)C-telopeptide. The distance between the alpha 1(II)N-telopeptide and alpha 1(II)C-telopeptide interaction sites, 137 residues, is equal to the length of the hole zone (0.6D) in a type II collagen fibril. This implies an antiparallel type II to type IX cross-linking relationship. Peptide analysis also revealed an unknown amino acid sequence linked to the COL2 cross-linking domains in both the alpha 1(IX) and alpha 3(IX) chains. Using antibodies to this novel peptide, its origin in the collagen alpha 3(IX)NC1 domain was established. In summary, the results confirm extensive covalent cross-linking between type IX and type II collagen molecules and reveal the existence of type IX-type IX bonding. These data provide a molecular basis for the proposed function of type IX collagen as a critical contributor to the mechanical stability and resistance to swelling of the collagen type II fibril framework of cartilage. PMID- 1429649 TI - The ATP-independent pathway in red blood cells that degrades oxidant-damaged hemoglobin. AB - Studies were carried out to characterize further the cytoplasmic ATP- and ubiquitin-independent proteolytic system in red blood cells that degrades hemoglobin damaged by exposure to oxidants (Fagan, J. M., Waxman, L., and Goldberg, A. L. (1986) J. Biol. Chem. 261, 5705-5713). Several proteases were ruled out as having a major role in the degradation of oxidant-treated hemoglobin (Ox-Hb). Acid hydrolases are not active in this process since the degradation of Ox-Hb has a pH optimum between 6 and 8. The calpains are also not involved since inhibitors of cysteine proteases (leupeptin and trans-epoxysuccinyl-L-leucylamido (3-methyl)butane) did not diminish the increased proteolysis in intact erythrocytes treated with oxidants or in lysates to which Ox-Hb was added. The degradation of Ox-Hb was unaffected by inhibitors of serine and aspartic proteases. Removal of the high M(r) multicatalytic proteinase by immunoprecipitation also did not significantly affect the degradation of Ox-Hb in erythrocyte lysates. The degradation of Ox-Hb was sensitive to metal chelators and sulfhydryl-modifying reagents but not to specific inhibitors of known metalloproteases. Insulin, which is rapidly degraded in lysates, completely blocked the degradation of Ox-Hb. Insulin- and Ox-Hb-hydrolyzing activity was also inhibited following immunoprecipitation of the 100-kDa metalloinsulinase. The metalloinsulinase, which is inhibited by sulfhydryl-modifying reagents and which requires divalent metals, may therefore participate in the degradation of hemoglobin damaged by oxidants in erythrocytes. PMID- 1429650 TI - Analysis of the amino acid sequence of the Pseudomonas aeruginosa galactophilic PA-I lectin. AB - Based on the NH2-terminal 30-amino acid sequence of Pseudomonas aeruginosa galactophilic PA-I lectin, two degenerate primer oligonucleotides were synthesized and used in polymerase chain reaction with the bacterial chromosomal DNA as a template. A predominant DNA fragment of the appropriate size was radiolabeled and used as a probe for screening a P. aeruginosa genomic lambda gt11 library. One positive clone carrying an insert of about 630 base pairs encompassing the entire PA-I lectin gene was isolated and found to contain a 369 base pair open reading frame between an initiation codon (19 base pairs downstream from the insertion site, subsequent to a Shine-Dalgarno sequence) and two consecutive stop codons, followed by an oligo (seven) A sequence, in a partial dyad symmetry. The deduced amino acid sequence shows excellent agreement with the quantitative amino acid analysis and a perfect match with the NH2 terminal amino acid sequence of the purified lectin. It reveals that the PA-I lectin subunit contains 121 amino acids (M(r) 12,754; pI 4.94) with a predominant central hydrophilic core between two hydrophobic domains. Secondary structure algorithms predict that it is rich in beta sheets and contains several highly antigenic epitopes, but no signal peptide. In the carboxyl region a potential glycosylation site (Asn-Asn-Ser) was identified. Comparative analyses of this lectin sequence with those of lectins from other sources, reported in the protein and gene data banks, did not reveal any extensive homology. PMID- 1429651 TI - Subunit folding and alpha delta heterodimer formation in the assembly of the nicotinic acetylcholine receptor. Comparison of the mouse and human alpha subunits. AB - We have used the mouse alpha (alpha M) and human alpha (alpha H) subunits to investigate the molecular mechanisms of assembly of the mammalian acetylcholine receptor (AChR) transiently expressed in COS cells. COS cells expressing hybrid receptors incorporating alpha H along with other mouse subunits exhibited a 2 fold higher level of surface alpha-bungarotoxin (BuTx) binding than cells expressing the wild-type mouse AChR. When expressed either alone or with the delta subunit in COS cells, alpha H acquired the BuTx binding conformation (alpha Tx) more efficiently than did alpha M. By oligonucleotide-directed mutagenesis we showed that 2 residues in the amino-terminal domain were responsible for the differences between alpha M and alpha H. Alpha MST, the modified mouse alpha subunit, both folded more efficiently to form alpha Tx and was more effective in forming a stable alpha delta heterodimer than was alpha M. The kinetics of alpha Tx and alpha delta heterodimer formation revealed that the delta subunit increased the conversion of immature forms of the alpha subunit into the BuTx binding form and therefore provides evidence for interaction between the delta subunit and the immature form of the alpha subunit. These results provide evidence of the importance of the amino-terminal domains of the AChR subunits in the assembly process. PMID- 1429652 TI - Incorporation of cytosine arabinoside monophosphate into DNA at internucleotide linkages by human DNA polymerase alpha. AB - The incorporation of cytosine arabinoside monophosphate (araCMP) into DNA at internucleotide linkages by DNA polymerase alpha (DNA pol alpha) has been investigated by using oligonucleotide primed DNA templates. The products of reactions catalyzed by DNA pol alpha in vitro were analyzed on polyacrylamide gels to measure insertion of araCMP, extension from an araCMP 3' terminus, and binding of the enzyme to an araCMP 3' terminus. The results show that insertion of araCMP opposite dGMP in the DNA template is about 3-fold less efficient than insertion of dCMP. Extension from an araCMP 3' terminus by addition of the next complementary nucleotide is approximately 2000-fold less efficient than extension from a correctly base-paired 3' terminus. In the absence of the second substrate, dNTP, DNA pol alpha binds with approximately equal affinities to DNA templates that contain oligonucleotide primers with araCMP or dCMP positioned at the 3' terminus. In the presence of dNTP, the enzyme extends the araCMP 3' terminus or dissociates, but it is not trapped at the araCMP 3' terminus in a nonproductive ternary complex as is observed at the ddCMP 3' terminus. To determine if slow phosphodiester bond formation contributes to the observed extension rate from the araCMP 3' terminus by DNA pol alpha, oligonucleotide primers with araCMP positioned at the 3' terminus were elongated by addition of the alpha phosphorothioate analogue of the next complementary nucleotide. The rate of extension from araCMP by addition of 2'-deoxyadenosine 5'-O-phosphorothioate (dAMP alpha S) was 6-fold slower than by addition of dAMP, indicating that bond formation is partially rate limiting in the extension reaction. Thus, inefficient extension from the araCMP 3' terminus is the major determinant contributing to the low incorporation frequency of araCMP into DNA by DNA pol alpha, and this inefficiency can be attributed, in part, to slower phosphodiester bond formation at the araCMP 3' terminus. PMID- 1429653 TI - Two genetically expressed troponin T fragments representing alpha and beta isoforms exhibit functional differences. AB - The carboxyl-terminal isoforms of troponin T (TnT), alpha and beta, differing in the sequence of a region near the COOH terminus, arise from alternative splicing of a primary transcript of the TnT gene and are expressed in a tissue-specific and developmentally regulated manner (Medford, R. M., Nguyen, H. T., Destree, A. T., Summers, E., and Nadal-Ginard, B. (1984) Cell 38, 409-421). To date, the beta isoform has not been studied directly at the protein level. To explore the potential functional differences between the alpha and beta sequences, we isolated two rabbit skeletal TnT cDNA clones: a full-length cDNA for a beta isoform and a partial-length cDNA for an alpha isoform. Two restriction fragments derived from the cDNA clones were used to direct overexpression, in Escherichia coli, of two TnT fragments, T2p-alpha and T2p-beta, each containing the last 108 amino acid residues of the alpha or beta isoform of TnT. Using purified T2p-alpha and T2p-beta along with fluorescent derivatives of troponin C (TnC) and alpha alpha-tropomyosin (Tm), we showed that T2p-alpha bound more strongly to TnC than did T2p-beta both in the presence and absence of Ca2+, and exhibited a higher affinity for Tm than did T2p-beta. More interestingly, the Ca2+ affinities of the Ca(2+)-specific regulatory sites of TnC in the T2p-alpha. TnC complex were found to be 3-fold higher than in T2p-beta.TnC complex. These results support the hypothesis that the sequence divergence between the alpha and beta isoforms of TnT may have functional significance in possibly contributing to the determination of the Ca2+ sensitivity of muscle fibers. PMID- 1429654 TI - Dominant negative mutants of ornithine decarboxylase. AB - Conserved lysines of mouse ornithine decarboxylase were individually mutated to arginines. The mutations at amino acid residues 69, 115, and 169 greatly reduced or abolished enzymatic activity. Lysine 69 is the site of Schiff base formation with the cofactor pyridoxal phosphate; the functional role of the other two lysines essential for activity is not known. Coexpression of wild type ornithine decarboxylase along with the lysine 115 to arginine mutant reduced the activity of the former without diminishing the amount of wild type protein. This form of negative complementation was seen when wild type and mutant protein were coexpressed either by in vitro translation or in bacteria. The data are consistent with the conclusion that a wild type and mutant subunit form a heterodimer that is enzymatically inactive. PMID- 1429655 TI - Opening of the replication origin of Escherichia coli by DnaA protein with protein HU or IHF. AB - Opening of the three tandem repeats of a 13-mer in the replication origin (oriC) of Escherichia coli is a prime event in the replication in vitro of minichromosomes (Bramhill, D., and Kornberg, A. (1988) Cell 54, 915-918). DnaA, the initiator protein, requires protein HU or IHF, along with a millimolar level of ATP and negative superhelical density in the plasmid to open this region. The extent of opening, as judged by cleavage by a single-strand-specific endonuclease (i.e. P1 nuclease), correlated closely with replication of the oriC plasmid. In an initial complex, preceding opening of the 13-mers, the footprint of DnaA protein bound by ATP covered its four 9-mer recognition sequences. The footprint of the nucleotide-free form of the protein, by contrast, was more extensive and thus, less specific. PMID- 1429656 TI - Opposed actions of regulatory proteins, DnaA and IciA, in opening the replication origin of Escherichia coli. AB - The opening of the three tandem 13-mers (iterons) in the replication origin (oriC) of Escherichia coli by DnaA protein, assisted by protein HU or IHF (Hwang, D. S., and Kornberg, A. (1992) J. Biol. Chem. 267, 23083-23086), represents an essential early stage in the initiation of chromosomal replication (Bramhill, D., and Kornberg, A. (1988) Cell 54, 915-918). We now show by mutational alterations of the 13-mer region that oriC function, both in vitro and in vivo, requires AT richness in the left 13-mer and sequence specificity in the middle and right 13 mers. Interactions of DnaA protein with the middle and right 13-mers are crucial for the opening of the region. Binding of the protein to the top strand of the 13 mers appeared to maintain single-strandedness in the bottom strand. IciA protein, the inhibitor of initiation, binds the three 13-mers and blocks the opening of the region. The degrees of inhibition by IciA protein of 13-mer opening and of oriC plasmid replication observed with mutant forms of the 13-mers could be correlated with the binding affinity of IciA protein. Whereas the binding of IciA protein to the 13-mers did not affect the binding of DnaA protein to its four 9 mers boxes, interaction of DnaA protein with the 13-mers was blocked. The selective interactions of DnaA and IciA proteins with the 13-mer region appear to be components of the on/off switch that controls initiation of E. coli chromosomal replication. PMID- 1429657 TI - Biochemical and genetic dissection of the Saccharomyces cerevisiae RNA polymerase C53 subunit through the analysis of a mitochondrially mis-sorted mutant construct. AB - RPC53 has previously been shown to encode an essential subunit required for tRNA gene transcription by RNA polymerase C in vivo (Mann, C., Micouin, J.-Y., Chiannilkulchai, N., Treich, I., Buhler, J.-M., and Sentenac, A. (1992) Mol. Cell. Biol. 12, in press). In this paper, we have determined that an unusual rho+ lethality associated with the rpc53::HIS3-1 disruption mutation is due to the inadvertent formation of a Pet56-C53 fusion protein. This fusion protein is missorted to mitochondria, thereby reducing the quantity of the C53 subunit available for RNA polymerase C assembly. We show that the carboxyl-terminal region of C53 contains the essential functional domain of the subunit and that a mutant RNA polymerase containing only this domain is thermolabile for its function in vivo and in vitro. The thermolability of the carboxyl-terminal C53 domain is suppressed by five different genes on multicopy plasmids, including RPC160, encoding the largest subunit of RNA polymerase C and SSD1/SRK1, which has been implicated in the activity of protein phosphatases. PMID- 1429658 TI - cDNA cloning of MEV, a mutant protein that facilitates cellular uptake of mevalonate, and identification of the point mutation responsible for its gain of function. AB - We report the expression cloning of pMev, a cDNA that facilitates cellular uptake of mevalonate. pMev was isolated from the met-18b-2 clone of Chinese hamster ovary (CHO) cells, which were selected for growth in low concentrations of mevalonate when synthesis is blocked by compactin (Faust, J. R., and Krieger, M. (1987) J. Biol. Chem. 262, 1996-2004). pMev encodes a 494-residue protein, Mev, that is predicted to have 12 membrane-spanning regions, consistent with a membrane transporter. Surprisingly, levels of Mev mRNA and protein are similar in CHO and met-18b-2 cells. The Mev gene differs from the wild-type gene by a single base change that substitutes a cysteine for phenylalanine in the 10th membrane spanning region. met-18b-2 cells are heterozygous for this dominant gain-of function mutation. Transfection of a cDNA encoding pMev, but not the wild-type cDNA, elicited a marked increase in [3H]mevalonate uptake and incorporation into cellular lipids in stably and transiently transfected cells. The availability of pMev will facilitate studies of [3H]mevalonate incorporation into trace products, including p21ras and other prenylated proteins. PMID- 1429659 TI - Sphingosine-1-phosphate, a metabolite of sphingosine, increases phosphatidic acid levels by phospholipase D activation. AB - Sphingosine and sphingosine-1-phosphate, metabolites of membrane sphingolipids, have recently been shown to stimulate release of calcium from internal sources and to increase proliferation of quiescent Swiss 3T3 fibroblasts (Zhang, H., Desai, N. N., Olivera, A., Seki, T., Brooker, G., and Spiegel, S. (1991) J. Cell Biol. 114, 155-167). The present study demonstrates that mitogenic concentrations of sphingosine induce early increases in sphingosine-1-phosphate levels which precede the increase in the potent mitogen, phosphatidic acid. Sphingosine-1 phosphate itself induces a more rapid increase in phosphatidic acid, thus suggesting that it may mediate the effects of sphingosine on phosphatidic acid accumulation. The concentration dependence for the formation of phosphatidic acid induced by sphingosine-1-phosphate correlates with its effect on DNA synthesis. Similar to sphingosine, sphingosine-1-phosphate also stimulates the activity of phospholipase D, although a significant effect is observed at a much lower concentration. However, in contrast to previous reports with sphingosine, sphingosine-1-phosphate does not inhibit the phosphatidic acid phosphohydrolase activity in cell homogenates. Thus, in addition to its effect on mobilization of calcium, sphingosine-1-phosphate can increase the level of phosphatidic acid, most likely via activation of phospholipase D. We suggest that sphingosine-1 phosphate mediates the effect of sphingosine on phosphatidic acid accumulation in Swiss 3T3 fibroblasts and may regulate cellular proliferation by affecting multiple transmembrane signaling pathways. PMID- 1429660 TI - Activation of S6 kinase by repeated cycles of stretching and relaxation in rat glomerular mesangial cells. Evidence for involvement of protein kinase C. AB - Quiescent rat glomerular mesangial cells were exposed to repeated cycles of stretching and relaxation, and the effects on the rate of collagen production, proliferation, and S6 kinase activity were investigated. Stretch/relaxation induced increases in production of both collagen and non-collagenous proteins. Proliferation of mesangial cells was stimulated by stretch/relaxation and epidermal growth factor, but not by angiotensin II; however, administration of angiotensin II augmented stretch/relaxation-induced cell proliferation. Cytosolic S6 kinase activity was stimulated by stretch/relaxation, angiotensin II, epidermal growth factor, or phorbol 12-myristate 13-acetate. The increased S6 kinase activity was detectable within 30 min after initiation of stretch/relaxation and was blocked by either inhibitors of protein kinase C or prior down-regulation of protein kinase C following prolonged incubation with phorbol 12-myristate 13-acetate. Both translocation of protein kinase C from the cytosolic to the membrane fraction and phosphorylation of an endogenous 80-kDa protein were observed within 5 min of initiation of stretch/relaxation. These results demonstrate that in mesangial cells, mechanical factors alone can induce increases in production of collagen and non-collagenous proteins and in cell proliferation. The observation that stretch/relaxation induced stimulation of S6 kinase activity through protein kinase C-dependent mechanisms suggests that activation of protein kinase C may be a key event in initiating adaptive responses of mesangial cells to increased workload. PMID- 1429661 TI - 3'-->5' exonuclease in Drosophila mitochondrial DNA polymerase. Substrate specificity and functional coordination of nucleotide polymerization and mispair hydrolysis. AB - A mispair-specific 3'-->5' exonuclease copurifies quantitatively with the near homogeneous Drosophila gamma polymerase (Kaguni, L.S., and Olson, M.W. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6469-6473). The exonuclease and polymerase exhibit similar reaction requirements and optima, suggesting functional coordination of their activities. Under nonpolymerization conditions, the 3'-->5' exonuclease hydrolyzes 3'-terminal mispairs approximately 15-fold more efficiently than 3'-terminal base pairs on primed single-stranded DNA substrates, whereas it does not discriminate between any of three specific mispairs (dAMP:dAMP;dGMP:dGMP; dGMP:dAMP). Under polymerization conditions, gamma polymerase does not extend a 3'-terminal mispair from the "stationary" state, even in the presence of a large excess of the next correct nucleotide. Instead, 3'-terminal mispairs are hydrolyzed quantitatively by the 3'-->5' exonuclease over the reaction time course. During DNA synthesis by gamma polymerase in the "polymerization" mode, limited misincorporation and subsequent mispair extension do occur. Here, it appears that misincorporation and not mispair extension is rate-limiting. Template-primer challenge experiments suggest that the mechanism of template-primer transfer from the 3'-->5' exonuclease active site to the DNA polymerase active site is intermolecular; transfer from the exonuclease to polymerase mode appears to require dissociation and reassociation of mitochondrial DNA polymerase. PMID- 1429662 TI - Assembly and secretion of fibrinogen. Degradation of individual chains. AB - Hep G2 cells produce surplus A alpha and gamma fibrinogen chains. These excess chains, which are not secreted, exist primarily as free gamma chains and as an A alpha-gamma complex. We have determined the intracellular location and the degradative fate of these polypeptides by treatment with endoglycosidase-H and by inhibiting lysosomal enzyme activity, using NH4Cl, chloroquine, and leupeptin. Free gamma chain and the gamma component of A alpha-gamma are both cleaved by endoglycosidase-H, indicating that the gamma chains accumulate in a pre-Golgi compartment. Lysosomal enzyme inhibitors did not affect the disappearance of free gamma chains but inhibited A alpha-gamma by 50%, suggesting that A alpha-gamma is degraded in lysosomes. The degradative fate of individual chains was determined in transfected COS cells which express but do not secrete single chains. Leupeptin did not affect B beta chain degradation, had very little affect on gamma chain, but markedly inhibited A alpha chain degradation. Antibody to immunoglobulin heavy chain-binding protein (GRP 78) co-immunoprecipitated B beta but not A alpha or gamma chains. Preferential binding of heavy chain-binding protein to B beta was also noted in Hep G2 cells and in chicken hepatocytes. Taken together these studies indicate that B beta and gamma chains are degraded in the endoplasmic reticulum, but only B beta is bound to BiP. By contrast A alpha chains and the A alpha-gamma complex undergo lysosomal degradation. PMID- 1429663 TI - Sequence of the fifth largest subunit of RNA polymerase II from plants. AB - An affinity-purified antibody raised against the fifth largest subunit of cauliflower (Brassica oleracea) RNA polymerase II was used to screen an expression library and isolate an Arabidopsis thaliana cDNA clone. This cDNA clone was used to isolate a soybean (Glycine max) cDNA clone, and both clones were sequenced. The open reading frames contain 176 amino acids and predict polypeptides of 19.5 and 19.6 kDa for Arabidopsis and soybean, respectively. The amino acid sequences of the Arabidopsis and soybean polypeptides are 91.5% identical. The fifth largest subunit in plant RNA polymerase II is present at unit stoichiometry in purified enzyme and does not dissociate from the holoenzyme during nondenaturing polyacrylamide gel electrophoresis. The gene encoding the 19.5-kDa subunit has been isolated and sequenced from Arabidopsis. The gene is single copy and contains five introns. The size of the mRNA encoding this RNA polymerase II subunit in Arabidopsis and soybean is approximately 1 kilobase. None of the published yeast or animal RNA polymerase subunit sequences show similarity to the fifth largest subunit in plants. PMID- 1429664 TI - Strand-selective repair of DNA damage in the yeast GAL7 gene requires RNA polymerase II. AB - We examined the role of transcription in directing repair of DNA damage in active genes by comparing the repair of thymine glycols produced by H2O2 and of UV induced pyrimidine dimers on each strand of the GAL7 gene of Saccharomyces cerevisiae. Repair of both thymine glycols and pyrimidine dimers on the transcribed strand of the gene occurs two to three times faster than on its nontranscribed strand or in the genome overall. When the gene is inactive, no preferential or strand-selective repair is observed. Using a yeast strain containing a temperature-sensitive mutation in one of the subunits of RNA polymerase II, we find that inactivating RNA polymerase II by shifting the cells to the nonpermissive temperature during repair eliminates the strand selectivity of repair under conditions where repair on the nontranscribed strand of the gene and in the genome overall are only slightly affected. Our observation of strand selective repair of thymine glycols in the GAL7 gene is the first evidence that this repair process occurs for a nonbulky lesion. In addition, we demonstrate that the transcriptional complex plays a critical role in directing repair to the transcribed strand of active genes. PMID- 1429665 TI - The Q205LGo-alpha subunit expressed in NIH-3T3 cells induces transformation. AB - The growth functions of the heterotrimeric G protein G(o) was studied by expression in heterologous systems. The alpha-subunit of G(o) was mutated to convert Gln-205 to Leu (Q205L). Mutation of this conserved glutamine residue in G protein alpha-subunits is thought to persistently activate G proteins by inhibiting their GTPase activity. The wild type and mutant G(o)-alpha subunits were expressed in NIH-3T3 fibroblasts. These cells do not contain any measurable amounts of G(o)-alpha mRNA or protein. Transfection of wild type or Q205LG(o) alpha subunit cDNA under the control of a dexamethasone-inducible promoter results in dexamethasone-dependent transcription of the mRNA and expression of the protein. The Q205LG(o)-alpha, but not wild type G(o)-alpha, stimulates mitogenesis in NIH-3T3 fibroblasts without significantly stimulating phospholipase C activity. Continuous expression of mutant G(o)-alpha induces focus formation, whereas transfections with vector alone or vector containing the native G(o)-alpha cDNA were without significant transforming effect in NIH-3T3 cells. Q205L G(o)-alpha did not induce focus formation in RAT-1 fibroblasts. Q205LG(o)-alpha-transformed NIH-3T3 cells are capable of anchorage-independent growth, as assessed by colony formation in soft agar. Q205LG(o)-alpha transformed cells induced tumors when injected into Nu/Nu mice. These results indicate that mutant G(o)-alpha subunits whose GTPase activity is presumably inhibited can induce the neoplastic transformation of NIH-3T3 cells in a phospholipase C independent manner. PMID- 1429666 TI - Differential effects of heat shock and UVB light upon stress protein expression in epidermal keratinocytes. AB - Heat stress and ultraviolet light in the UVB range ("sunburn spectrum," 290-320 nm) were found to alter the synthesis of specific proteins in cultured keratinocytes derived from mouse skin. Using giant two-dimensional gels, approximately 2,000 cellular polypeptides labeled with [35S]methionine at 4-5 h after exposure to heat or to UVB were analyzed. Cells conditioned at sublethal temperatures (42 degrees C for 1 h, or 47 degrees C for 15 min) developed thermotolerance, while cells conditioned with UVB did not develop thermotolerance. Under these heat or UVB conditions, 19 stress proteins were observed. Proteins fell into three classes based upon their inducibility by heat or UVB, dose-response, and induction mechanism (transcriptional versus post transcriptional) as defined by metabolic blockade with cordycepin (3' deoxyadenosine). Class 1 proteins were inducible only by heat shock. They included three major heat-shock proteins (hsp 72, hsp 78, hsp 90) and a 42.5-kDa, pI 5.43 protein, and all were induced at the transcriptional level. Class 2 proteins were inducible by heat and by UVB. These included hsp 110 and eight additional polypeptides. All but one were affected by heat at the post transcriptional level and were induced by UVB at both low (20 mJ/cm2) and high (80 mJ/cm2) doses. Class 3 proteins were inducible only at high UVB doses (survival < 10%). Class 1 and Class 2 proteins could be functionally involved in thermotolerance, while Class 3 proteins are more likely related to damage or cell death. PMID- 1429667 TI - N-myristoylation of the rod outer segment G protein, transducin, in cultured retinas. AB - Bovine retinas incubated with [3H]myristic acid incorporated detectable radiolabel into only a few proteins. The most heavily labeled was the alpha subunit of the rod outer segment G protein transducin (Gt alpha). The radiolabeled protein was specifically eluted from illuminated membranes in the presence of GTP, displaying the unique solubility properties of Gt alpha. It comigrated with Gt alpha in electrophoresis and chromatography and was immunoprecipitated by Gt alpha-specific antibodies. The radiolabel was confirmed by hydrolysis, chemical derivatization, and chromatography to be amide-linked myristic acid. The solubility of the myristoylated Gt alpha indicates that myristoylation is not sufficient to cause tight membrane association of this normally membrane-bound subunit. Incorporation of [3H]myristate was blocked by the protein synthesis inhibitor cycloheximide, suggesting that that fatty acid group is introduced during or soon after translation in the rod inner segment. PMID- 1429668 TI - Characterization of recombinant von Willebrand factor corresponding to mutations in type IIA and type IIB von Willebrand disease. AB - Type IIA and IIB von Willebrand disease (vWD) result from defects in von Willebrand factor (vWF). Although both type IIA and IIB vWD are characterized by the absence of high molecular weight multimers in plasma, vWF from patients with type IIA vWD demonstrates a decreased affinity for the platelet receptor glycoprotein Ib (GPIb), whereas vWF from patients with type IIB vWD show an increased affinity for GPIb. To investigate how structural alterations in vWF affect its interaction with GPIb, we reproduced the reported potential mutations in type IIA and IIB vWD in vWF cDNA and expressed the recombinant proteins in COS 1 cells. The type IIA vWF potential mutation was represented by a G-->A transversion which results in the substitution of Lys for Glu at position 875 in the mature vWF subunit (rvWFLys875). The type IIB vWF mutation corresponds to a duplicated ATG codon, resulting in three contiguous methionines starting at position 540-541 in the normal vWF sequence (rv-WFduplMet540-541). The subunit composition and multimeric structure of both mutant proteins were similar to the wild-type rvWF. The rvWFLys875 bound to fixed platelets in the presence of ristocetin similar to wild-type rvWF. The rvWFduplMet540-541 bound to fixed platelets in the absence of agonist. The rvWFLys875 appears to interact normally with GPIb, and the decreased affinity for the platelet receptor observed in plasma is probably a consequence of prior reduction in multimeric size resulting from the defect. In contrast, the duplication of Met540-541 increases the reactivity of vWF for its platelet receptor. PMID- 1429669 TI - Paneth cells of the human small intestine express an antimicrobial peptide gene. AB - Mucosal surfaces of several organ systems are important interfaces for host defense against microbes. Recent evidence suggests that antimicrobial peptides contribute to the defense of these surfaces. Defensins are one family of antimicrobial peptide, but their known distribution in humans has been limited to four members found in cells of myeloid origin. We sought to determine if the human defensin family was more complex. We found that the family of human defensins is diverse and is not restricted to expression in leukocytes. Southern blot and genomic clone analyses reveal that numerous defensin-related sequences are present in the human genome. A gene for a new human defensin family member was characterized. This gene, designated human defensin-5, is highly expressed in Paneth cells of the small intestine. This is the first example of an antimicrobial peptide gene expressed in an epithelial cell in humans. The data support the hypotheses that epithelial defensins equip the human small bowel with a previously unrecognized defensive capability which would augment other antimicrobial defenses. PMID- 1429670 TI - Amino acid sequence of the human protein synthesis initiation factor eIF-4 gamma. AB - Eukaryotic protein synthesis initiation factor (eIF) 4 gamma, also known as p220, is a component of the protein complex eIF-4, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome. Peptide sequence data from rabbit reticulocyte eIF-4 gamma was used to synthesize oligonucleotide probes and polymerase chain reaction primers. These were used to screen lambda-cDNA libraries from rabbit and human brain, yielding a partial rabbit and a complete human cDNA sequence of 5.1 kilobases. Northern blot and primer extension analysis indicated that the cDNA sequence was complete. To confirm that the cDNA represented that of eIF-4 gamma, three peptides were synthesized based on cDNA sequences and used to produce anti-peptide antibodies. The antibodies specifically recognized intact eIF-4 gamma and its cleavage products following poliovirus infection. The eIF-4 gamma mRNA contains AUG codons at nucleotides 6, 67, 90, 165, and 369, but only the last is followed by a long open reading frame. The eIF-4 gamma polypeptide is 154 kDa (1396 amino acid residues) and contains sequence motifs of potential interest: a sequence (AGLGPR) that is similar to the substrate recognition sequence of protease 2A from rhinovirus serotype 14, five PEST regions with scores greater than 10, which are characteristic of rapidly degraded proteins, stretches of polyglutamic acid, and numerous potential phosphorylation sites. PMID- 1429672 TI - Processing and secretion of tumor necrosis factor alpha in endotoxin-treated Mono Mac 6 cells are dependent on phorbol myristate acetate. AB - Lipopolysaccharide (LPS, endotoxin) is a potent stimulator of tumor necrosis factor alpha (TNF alpha) synthesis and secretion in mouse macrophage tumor cells (Golenbock, D. T., Hampton, R. Y., Qureshi, N., Takayama, K., and Raetz, C. H. R. (1991) J. Biol. Chem. 266, 19490-19498). In contrast, addition of LPS (10 ng/ml) to human monomyelocytic (Mono Mac 6) cells induces very little production of TNF alpha, as judged by immunoassay of the growth medium. When 30 ng/ml 4-beta phorbol-12-myristate 13-acetate (PMA) is added together with LPS, large amounts of TNF alpha are secreted. PMA alone is inactive. Maximal TNF alpha levels in the medium are achieved at 1 ng/ml of LPS. Protein kinase C inhibitors, such as H7 (1 (5-isoquinolinylsulfonyl)-2-methylpiperazine), staurosporine, and sphingosine, reduce TNF alpha secretion stimulated by PMA. The effect of PMA has been investigated at each stage of TNF alpha biogenesis. Treatment of Mono Mac 6 cells with LPS alone results in rapid, transient, and full expression of TNF alpha mRNA. Concomitant addition of PMA does not increase TNF alpha mRNA synthesis any further, but it prolongs the half-life of TNF alpha mRNA about 3-fold. However, mRNA stabilization does not account for the striking effect of PMA on TNF alpha secretion. Analysis of TNF alpha synthesis and secretion by immunoprecipitation indicates that LPS alone is fully effective in stimulating the formation of the intracellular 26-kDa TNF alpha precursor. LPS alone is not sufficient to allow processing of the precursor and secretion of mature 17-kDa TNF alpha. The rate of TNF alpha secretion observed immediately after the addition of PMA to LPS pretreated cells is similar to the maximum rate from LPS/PMA-treated cells, but without the lag observed in cells after being exposed to LPS and PMA simultaneously. In summary, PMA is required for the completion of TNF alpha precursor processing and secretion in LPS-treated human Mono Mac 6 cells, whereas murine RAW cells are able to complete the terminal steps of TNF alpha processing in the absence of PMA. PMID- 1429671 TI - Characterization of transport-mediated methotrexate resistance in human tumor cells with antibodies to the membrane carrier for methotrexate and tetrahydrofolate cofactors. AB - An earlier report (Matherly, L. H., Czajkowski, C. A., and Angeles, S. M. (1991) Cancer Res. 51, 3420-3426) described a K562 human erythroleukemia line (K562.4CF), characterized by an elevated uptake capacity for methotrexate (MTX) and 5-formyltetrahydrofolate, and the identification of a highly glycosylated membrane transporter (GP-MTX) by radioaffinity labeling with N-hydroxysuccinimide [3H] methotrexate. In the present study, radioaffinity-labeled GP-MTX from K562.4CF cells was isolated by Ricinus communis agglutinin I-agarose affinity chromatography, coupled with gel filtration and preparative electrophoresis. Antiserum to the purified, radio-labeled protein was raised in a rabbit and screened by immunoblot analysis of K562.4CF plasma membrane proteins or purified GP-MTX. The antiserum detected a broad GP-MTX band centered at 92 kDa on 7.5% gels. On 4-10% gels, the apparent molecular mass for GP-MTX shifted to 99 kDa. Antiserum specificity was established by quantitatively converting the immunoreactive glycoprotein in plasma membrane homogenates to its N- and O deglycosylated forms with N- and O-glycanases, respectively. Whereas the methotrexate uptake capacity of K562.4CF cells was elevated 6.1-fold over parental cells, the GP-MTX content on immunoblots was increased approximately 3 fold. For two methotrexate-resistant K562 lines (33- and 70-fold), decreased drug uptake (28 and 18% of parental levels) closely correlated with their reduced GP MTX contents. A GP-MTX isoform was also detected on immunoblots of membrane proteins from CCRF-CEM human lymphoblastic leukemia cells. With a transport impaired CCRF-CEM line (13% of wild type uptake), an aberrant electrophoretic migration for GP-MTX was observed, establishing the presence of structural modifications in the transport protein. These structural differences were independent of carrier glycosylation since they were detected following the glycosidase treatments. These findings implicate important roles for distinct carrier-specific alterations in the expression of diminished drug transport in methotrexate-resistant human tumor cells. PMID- 1429673 TI - Assembly regulatory domain of glial fibrillary acidic protein. A single phosphorylation diminishes its assembly-accelerating property. AB - Phosphorylation of glial fibrillary acidic protein (GFAP) induces disassembly of the filaments. An amino-terminal fragment of bovine GFAP (G-Hf) was produced by lysylendopeptidase digestion. G-Hf formed ribbon-like filaments in the presence of GFAP even in low ionic strength, whereas the fragment itself did not form any structures. Only one (PK3) of the five V8 protease fragments of G-Hf accelerated GFAP assembly to the same degree as G-Hf did, whereas the other fragments did not. When PK3 was cleaved into two fragments, it lost the assembly-accelerating property. The sequence of PK3 was determined as RRRVTSATRRSYVSSSE, which corresponded to residues 3-19 of porcine GFAP. It was concluded that PK3 contains a sequence indispensable for GFAP assembly and that neither PK1 (RRRVTS) nor PK2 (ATRRSYVSSSE) included all of the sequence. A single phosphorylation of PK3 by cyclic AMP-dependent protein kinase diminished its assembly-accelerating property. The phosphorylation site was determined as Ser-12 of porcine GFAP. It was shown that single phosphorylation of the amino-terminal head domain, which contains an indispensable sequence for GFAP assembly, might be sufficient for GFAP disassembly. PMID- 1429674 TI - A monoclonal antibody against a Na(+)-L-glutamate cotransporter from rat brain. AB - A monoclonal mouse IgM antibody (Z8E9) was raised against the Na(+)-L-glutamate cotransporter from rat brain. In a preparation of brain plasma membrane vesicles, Z8E9 binds specifically to a polypeptide with an apparent molecular weight of 70,000 and inhibits Na+ gradient-dependent L-glutamate cotransport (up to 50%) in brain membrane vesicles. In the membrane vesicles, the antibody does not alter the membrane permeability for Na+ and K+ nor the Na+ gradient-dependent uptake of gamma-aminobutyric acid. Kinetic experiments showed that Z8E9 does not alter the K0.5 values for L-glutamate and Na+ activation of L-glutamate transport. However, an apparent cooperativity observed for L-glutamate activation was increased, and the Vmax of L-glutamate transport was decreased. Immunostaining of rat cerebellum identified antigenic sites of Z8E9 in Golgi epithelial cells and astrocytes (by light and electron microscopy), whereas no labeling at nerve terminals was detected. The data suggest that a component of a Na(+)-L-glutamate cotransporter subtype has been identified that is specific for glia cells in brain. PMID- 1429675 TI - Mechanisms of subcellular cytosolic Ca2+ signaling evoked by stimulation of the vasopressin V1a receptor. AB - Receptor activation may result in distinct subcellular patterns of Ca2+ release. To define the subcellular distribution of Ca2+i signals induced by stimulation of the vasopressin V1a receptor, we expressed the cloned receptor in Xenopus oocytes. Oocytes were then loaded with fluo-3 and observed using confocal microscopy. Vasopressin induced a single concentric wave of increased Ca2+ that radiated inward from the plasma membrane. With submaximal stimulation, however, regions of the Ca2+ wave spontaneously reorganized into repetitive (oscillatory) waves. Focal stimulation of a small part of the plasma membrane resulted in a Ca2+ wave which began at the point of stimulation, radiated toward the center of the cell, then reorganized into multiple foci of repetitive, colliding waves and spirals of increased Ca2+i. The pattern of Ca2+ signaling induced by focal or global stimulation was not altered in Ca(2+)-free medium, although signals did not propagate as fast. Finally, subcellular Ca2+ signaling patterns induced by vasopressin were inhibited by caffeine, while neither vasopressin nor microinjection of inositol trisphosphate blocked caffeine-induced increases in cytosolic Ca2+. Thus, stimulation of the V1a receptor in this cell system induces a complex pattern of Ca2+ signaling which is influenced by (1) the magnitude of the stimulus, (2) the distribution of the surface receptors that are stimulated, and (3) mobilization of Ca2+ from the extracellular space as well as from two distinct endogenous Ca2+ pools. The manner in which a single type of receptor is activated may represent an important potential mechanism for subcellular Ca2+i signaling. PMID- 1429676 TI - Differential regulation of the atrial isoforms of the myosin light chains during striated muscle development. AB - We have isolated a cDNA that encodes the human regulatory myosin light chain isoform predominant in adult atrial muscle. The cDNA contains an open reading frame of 175 amino acids and encodes a hydrophilic protein of a largely helical structure with two potential phosphorylation sites. The protein is different from any other regulatory myosin light chain so far described and is the product of a previously uncharacterized single copy gene. An isoform-specific probe was used to analyze the expression of this isoform in adult muscle and in cardiac and skeletal muscle development in vivo and in vitro. Parallel analysis of the corresponding human alkali myosin light chain (predominant in adult atrium) showed that both isoforms are expressed in early heart development, in both atrium and ventricle. Although the atrial alkali light chain is expressed throughout embryonic striated muscle development, the regulatory myosin light chain was not detected in skeletal myogenesis in vivo or in vitro. Thus the atrial isoforms are not universally or exclusively "paired" and can be independently regulated. We propose that the manner in which these particular isoforms fulfill the functional requirements of the muscle at different developmental times may have direct impact on their regulation. PMID- 1429677 TI - Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. AB - Transforming growth factor (TGF)-beta and interleukin (IL)-10 inhibited lipopolysaccharide (LPS)-induced macrophage production of the inflammatory cytokines tumor necrosis factor-alpha (TNF), IL-1 alpha, and IL-1 beta by contrasting post-transcriptional mechanisms. TGF-beta acted slowly and late, as it required 12-16 h to exert a suppressive effect, and inhibited TNF production even when added 6 h after LPS. TGF-beta affected neither the level of TNF mRNA, the release of preformed TNF nor the degradation of TNF. Thus, TGF-beta appeared to inhibit translation of TNF mRNA. IL-10 not only suppressed TNF release to a 25 fold greater extent than TGF-beta, but also inhibited release of IL-1. In contrast to TGF-beta, IL-10 acted on an early step in cytokine production, its effect being maximal 3 h after addition of LPS. Unlike TGF-beta, IL-10 markedly suppressed TNF, IL-1 alpha, and IL-1 beta mRNA levels. However, this was accomplished without suppressing transcription of the corresponding genes. Moreover, cycloheximide antagonized the IL-10-dependent reduction in cytokine mRNA levels. Thus, IL-10 may induce a ribonuclease active on cytokine transcripts or may induce a protein that enhances the susceptibility of TNF, IL-1 alpha, and IL-1 beta mRNAs to ribonucleolytic action. We conclude that IL-10 and TGF-beta induce different phenotypes of macrophage deactivation, and deactivate macrophages by different mechanisms: IL-10 promotes degradation of cytokine mRNA, while TGF-beta primarily suppresses translation. PMID- 1429678 TI - Evidence for two conformers of the beta subunit of tryptophan synthase in solution. AB - To explain our finding that the dimeric beta subunit of tryptophan synthase is only 50% inactivated by beta-chloro-L-alanine (Ahmed, S. A., Ruvinov, S. B., Kayastha, A. M., and Miles, E. W. (1991) J. Biol. Chem. 266, 21548-21557), we have extended our investigation using spectroscopic, steady-state kinetic, and electrophoretic methods. The spectroscopic properties of the half-active beta 2 dimer and the reactivation after alkali treatment show that the inactivation proceeds by an "enamine" mechanism. Although the fully active beta 2 dimer associates with the tryptophan synthase alpha subunit to form alpha 2 beta 2 complex, the inactive beta subunits in the half-active enzyme associate weakly or not at all with the alpha subunit. Our results provide evidence for two conformers of the beta subunit in solution: one is rapidly inactivated by beta chloro-L-alanine and the other is not inactivated. Thermal inactivation studies and non-denaturing polyacrylamide gel electrophoresis of the half-active enzyme show that the beta 2 dimer exists in both homologous and heterologous combinations of these two forms. After removal of the reaction products and unreacted beta-chloro-L-alanine from the half-active beta 2 dimer by gel filtration, further incubation with beta-chloro-L-alanine results in the loss of 50% of the remaining activity. This result suggests that the subunits undergo rearrangement via an intermediate monomer form to regenerate the two conformers of the active beta subunit. This mechanism of rearrangement is supported by our finding that the extent of inactivation increases at lower concentrations of the beta 2 dimer. PMID- 1429679 TI - alpha A-crystallin is expressed in non-ocular tissues. AB - alpha-Crystallin, the predominant structural protein of the ocular lens, has been considered to be composed of two subunits, alpha A-crystallin and alpha B crystallin. Of these two, alpha B-crystallin has been previously shown to be an extralenticular protein while alpha A-crystallin has been considered to be a lens specific polypeptide. Using an antiserum directed against an N-terminal peptide of alpha-crystallin, we have detected a 20-kDa protein in various rat tissues including the brain, liver, lung, spleen, skin, and small intestine and in a number of established epithelial and fibroblast cell lines. PCR analysis of poly(A)-enriched RNA and Southern blot analysis indicated the presence of alpha A crystallin mRNA sequences in different non-lenticular tissues. Among the non ocular tissues examined, spleen showed the highest levels of alpha A-crystallin protein and mRNA. The identity of alpha A-crystallin sequences in the spleen was established by cloning and sequencing a polymerase chain reaction-amplified region of alpha A-crystallin mRNA. Sequences derived from spleen and eye revealed almost 100% identity at the nucleotide level. Interestingly, alpha A-crystallin and alpha B-crystallin seem to exist in an inverse quantitative relationship in the spleen and the heart, the two non-ocular tissues where they show highest concentrations, respectively. The known conserved evolution of alpha A-crystallin and the definitive demonstration of the non-ocular expression of this polypeptide suggest important non-crystallin functions for this protein. PMID- 1429680 TI - Ubiquitin-specific proteases of Saccharomyces cerevisiae. Cloning of UBP2 and UBP3, and functional analysis of the UBP gene family. AB - In eukaryotes, both natural and engineered ubiquitin (Ub) fusions to itself or other proteins are cleaved by processing proteases after the last (Gly76) residue of ubiquitin. YUH1 and UBP1, the genes for two ubiquitin-specific proteases of the yeast Saccharomyces cerevisiae, have been cloned previously and shown to encode nonhomologous proteins. Using an Escherichia coli-based genetic screen, we have isolated two other yeast genes for ubiquitin-specific proteases, named UBP2 and UBP3. Ubp2 (1,264 residues), Ubp3 (912 residues), and the previously cloned Ubp1 (809 residues) are largely dissimilar except for two short regions containing Cys and His which encompass their putative active sites. Neither of these proteases has sequence similarities to Yuh1. Both Ubp2 and the previously identified Ubp1 cleave in vitro at the C terminus of the ubiquitin moiety in natural and engineered fusions irrespective of their size, poly-Ub being the exception. However, both Ubp1 and Ubp2 are also capable of cleaving poly-Ub when coexpressed with it in E. coli, suggesting that such cleavage is largely cotranslational. Although inactive in E. coli extracts, Ubp3 was active with all of the tested ubiquitin fusions except poly-Ub when coexpressed with them in E. coli. Null yuh1 ubp1 ubp2 ubp3 quadruple mutants are viable and retain the ability to deubiquitinate ubiquitin fusions, indicating the presence of at least one more ubiquitin-specific processing protease in S. cerevisiae. PMID- 1429681 TI - Purification and properties of Saccharomyces cerevisiae RNA polymerase II general initiation factor a. AB - RNA polymerase II initiation factor a was purified to apparent homogeneity from yeast whole cell extract and consisted of two highly charged polypeptides with apparent masses of 66 and 43 kDa. Separation and renaturation of the subunits showed that both were required for transcription activity. The native mass of factor a was estimated to be 240-260 kDa by gel filtration, but its sedimentation rate in a glycerol gradient was similar to that of a much smaller globular protein, suggesting an extended conformation. Factor a was required for utilization of six different eukaryotic promoters in vitro, indicating a general role in promoter-directed transcription by yeast RNA polymerase II. PMID- 1429682 TI - G protein beta gamma subunits synthesized in Sf9 cells. Functional characterization and the significance of prenylation of gamma. AB - Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) consist of a nucleotide-binding alpha subunit and a high-affinity complex of beta and gamma subunits. There is molecular heterogeneity of beta and gamma, but the significance of this diversity is poorly understood. Different G protein beta and gamma subunits have been expressed both singly and in combinations in Sf9 cells. Although expression of individual subunits is achieved in all cases, beta gamma subunit activity (support of pertussis toxin-catalyzed ADP-ribosylation of rGi alpha 1) is detected only when beta and gamma are expressed concurrently. Of the six combinations of beta gamma tested (beta 1 or beta 2 with gamma 1, gamma 2, or gamma 3), only one, beta 2 gamma 1, failed to generate a functional complex. Each of the other five complexes has been purified by subunit exchange chromatography using Go alpha-agarose as the chromatographic matrix. We have detected differences in the abilities of the purified proteins to support ADP-ribosylation of Gi alpha 1; these differences are attributable to the gamma component of the complex. When assayed for their ability to inhibit calmodulin-stimulated type-I adenylylcyclase activity or to potentiate Gs alpha-stimulated type-II adenylylcyclase, recombinant beta 1 gamma 1 and transducin beta gamma are approximately 10 and 20 times less potent, respectively, than the other complexes examined. Prenylation and/or further carboxyl-terminal processing of gamma are not required for assembly of the beta gamma subunit complex but are indispensable for high affinity interactions of beta gamma with either G protein alpha subunits or adenylylcyclases. PMID- 1429683 TI - Alanine scanning mutagenesis identifies surface amino acids on domain II of Pseudomonas exotoxin required for cytotoxicity, proper folding, and secretion into periplasm. AB - Pseudomonas exotoxin A (PE) is a single polypeptide chain that contains 613 amino acids and is arranged into three major structural domains. Domain Ia is responsible for cell recognition, domain II for translocation of PE across the membrane, and domain III for ADP-ribosylation of elongation factor 2. Recombinant PE can be produced in Escherichia coli and is efficiently secreted into the periplasm when an OmpA signal sequence is present. To investigate the role of the amino acids located on the surface of domain II in the action of the toxin against mammalian cells, we substituted alanine for each of the 27 surface amino acids present in domain II. Surprisingly, all 27 mutant proteins had some alteration in cytotoxicity when tested on human A431 or MCF7 cells or mouse L929 cells. Native PE has a compact structure and therefore is relatively protease resistant and very little ADP-ribosylation activity is detected in the absence of the denaturing agents like urea and dithiothreitol. Several of the mutations resulted in altered protease sensitivity of the toxin. Seven of the mutant molecules exhibited ADP-ribosylation activity without urea and dithiothreitol, indicating they are partially unfolded. Out of these seven mutants, six had increased cytotoxic activity on at least one of the target cell lines and the other retained its native cytotoxic potency. PMID- 1429684 TI - The new enzymology of precursor processing endoproteases. PMID- 1429685 TI - Cell adhesion or integrin clustering increases phosphorylation of a focal adhesion-associated tyrosine kinase. AB - We have recently shown that changes in tyrosine phosphorylation of a 130-kDa protein(s) (pp130) may be involved in integrin signaling (Kornberg, L., Earp, H.S., Turner, C., Prokop, and Juliano, R. L. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 8392-8396). One component of the pp130 protein complex reacts with an antibody generated against p125fak, which is a focal contact-associated tyrosine kinase (Schaller, M.D., Borgman, C. A., Cobb, B. S., Vines, R. R., Reynolds, A. B., and Parsons, J. T. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 5192-5196). Both antibody-mediated integrin clustering and adhesion of KB cells to fibronectin leads to increased tyrosine phosphorylation of p125fak. The phosphorylation of p125fak is coincident with adhesion of cells to fibronectin and is maximal prior to cell spreading. Tyrosine phosphorylation of p125fak is induced when KB cells are allowed to adhere to fibronectin, collagen type IV, or laminin, but is not induced on polylysine. When KB cells are subjected to indirect immunofluorescence microscopy, p125fak colocalizes with talin in focal contacts. These data provide additional evidence that tyrosine kinases are involved in integrin signaling. PMID- 1429686 TI - Expression of a transmembrane phosphotyrosine phosphatase inhibits cellular response to platelet-derived growth factor and insulin-like growth factor-1. AB - Tyrosine phosphorylation is a mechanism of signal transduction shared by many growth factor receptors and oncogene products. Phosphotyrosine phosphatases (PTPases) potentially modulate or counter-regulate these signaling pathways. To test this hypothesis, the transmembrane PTPase CD45 (leukocyte common antigen) was expressed in the murine cell line C127. Hormone-dependent autophosphorylation of the platelet-derived growth factor (PDGF) and insulin-like growth factor-1 (IGF-1) receptors was markedly reduced in cells expressing the transmembrane PTPase. Tyrosine phosphorylation of other PDGF-dependent phosphoproteins (160, 140, and 55 kDa) and IGF-1-dependent phosphoproteins (145 kDa) was similarly decreased. Interestingly, the pattern of growth factor-independent tyrosine phosphorylations was comparable in cells expressing the PTPase and control cells. This suggests a selectivity or accessibility of the PTPase limited to a subset of cellular phosphotyrosyl proteins. The maximum mitogenic response to PDGF and IGF 1 in cells expressing the PTPase was decreased by 67 and 71%, respectively. These results demonstrate that a transmembrane PTPase can both affect the tyrosine phosphorylation state of growth factor receptors and modulate proximal and distal cellular responses to the growth factors. PMID- 1429687 TI - Interleukin-1 alpha induces the accumulation of cytosolic phospholipase A2 and the release of prostaglandin E2 in human fibroblasts. AB - Treatment of the human lung fibroblast cell line, WI-38, with interleukin-1 alpha (IL-1 alpha) results in a large increase in the production of cytosolic phospholipase A2 (cPLA2) and prostaglandin E2 (PGE2). The IL-1-induced accumulation of cPLA2 is closely correlated with increased PGE2 release. In contrast to cPLA2, the level of cyclooxygenase remains unchanged following IL-1 alpha treatment. The glucocorticoid, dexamethasone, blocks the IL-1 alpha mediated increases in both cPLA2 and PGE2 without affecting the cyclooxygenase level. Taken together, these data suggest that in these cells, the regulation of prostaglandin production by IL-1 and glucocorticoid can be attributed to the level of cPLA2. These results provide a new mechanism for the effect of IL-1 and glucocorticoids on eicosanoid synthesis and provide additional support for an important role of cPLA2 in the inflammatory response. PMID- 1429688 TI - A rise and fall in 1,2-diacylglycerol content signal hexamethylene bisacetamide induced erythropoiesis. AB - Previous studies have suggested a role for protein kinase C (PKC) during induction of murine erythroleukemia cell (MELC) differentiation by hexamethylene bisacetamide (HMBA) (Melloni, E., Pontremoli, S., Viotti, P. L., Patrone, M., Marks, P. A., and Rifkind, R. A. (1989) J. Biol. Chem. 264, 18414-18418). The present studies assess the effect of HMBA on the content of 1,2-diacylglycerol (DG), the physiologic activator of PKC, in MELC variants. Exposure of parental Sc9 cells to HMBA induced a rapid rise and fall in DG content. The DG level increased within seconds from 225 pmol.10(6) cells-1 to a maximum of 305 pmol.10(6) cells-1 at 5 min. Thereafter, DG content fell reaching control levels at 30 min and 46% of control at 4 h. Similar DG elevations were detected in HMBA resistant, phorbol ester-resistant, and vincristine-resistant MELC lines. Early DG elevation was followed by the characteristic rapid fall in both the phorbol ester-resistant and vincristine-resistant lines, both of which differentiate rapidly in response to HMBA. In contrast, in an HMBA-resistant MELC the DG level failed to fall for at least 10 h. Selection of HMBA-resistant cells for vincristine resistance restores both HMBA sensitivity and the rapid fall in DG content. Addition of a synthetic DG, 1-oleyl-2-acetyl glycerol (OAG), along with HMBA and every 2 h for the next 48 h blocked differentiation, as measured by accumulation of benzidine-reactive cells or by the commitment assay in methyl cellulose. However, if addition of OAG was delayed for just a few minutes, until endogenous DG levels began to fall, differentiation was no longer inhibited. Rapid elevation of DG content is the earliest reported event during HMBA action and a subsequent fall in the DG content appears to be a critical step in the process of commitment to terminal differentiation. PMID- 1429689 TI - Caffeine inhibits the agonist-evoked cytosolic Ca2+ signal in mouse pancreatic acinar cells by blocking inositol trisphosphate production. AB - The inhibitory effects of caffeine on receptor-activated cytosolic Ca2+ signal generation in isolated mouse pancreatic acinar cells were investigated. Using the ability of caffeine to quench Indo-1 fluorescence we measured simultaneously the free intracellular Ca2+ concentration ([Ca2+]i) and the intracellular caffeine concentration ([caffeine]i). We also measured inositol 1,4,5-trisphosphate (InsP3) production with a radioreceptor assay. When caffeine was added to the extracellular solution during a sustained receptor-activated increase in [Ca2+]i, [caffeine]i rose to its steady level within a few seconds. This was accompanied by a decrease of [Ca2+]i, which started only after [caffeine]i had reached an apparent threshold concentration (about 2 mM in the case of 0.5 microM acetylcholine (ACh) stimulation). Above this [caffeine]i level there was a linear relationship between [caffeine]i and [Ca2+]i. Throughout the caffeine exposure [Ca2+]i remained at a steady low level. Following removal of caffeine from the bath, [caffeine]i decreased to zero within seconds. There was no significant increase in [Ca2+]i until [caffeine]i had been reduced to the threshold level (about 2 mM at 0.5 microM ACh). Caffeine inhibited Ca2+ signals evoked by ACh, cholecystokinin, and ATP and also inhibited signals generated in the absence of external Ca2+. Caffeine application had the same effect as removal of agonist allowing recovery from apparent desensitization. Caffeine inhibited the agonist evoked production of InsP3 in a dose-dependent manner. Our results demonstrate the acute and reversible dose-dependent inhibition of agonist-evoked cytosolic Ca2+ signal generation due to rapid intracellular caffeine accumulation and washout. The inhibition can be explained by the reduction of agonist-evoked InsP3 production. PMID- 1429690 TI - Botulinum neurotoxins are zinc proteins. AB - The available amino acid sequences of 150-kDa botulinum and tetanus neurotoxins show the presence of a closely homologous segment in the middle of the light chain (NH2-terminal 50 kDa), which is the intracellularly active portion of the toxin. This segment contains the zinc binding motif of metalloendopeptidases, HEXXH. Atomic adsorption analysis of botulinum neurotoxins (serotypes A, B, and E) made on the basis of this observation demonstrated the presence of one zinc atom/molecule of 150-kDa neurotoxin. Conditions were found for the removal of the zinc ion with chelating agents and for the restoration of the normal metal content. The conserved segment, which includes the zinc binding motif, was synthesized and shown to bind [65Zn]2+. Chemical modification experiments indicated that two histidines and no cysteines are involved in Zn2+ coordination in agreement with a probable catalytic role for the zinc ion. The present findings suggest the possibility that botulinum neurotoxins are zinc proteases. PMID- 1429691 TI - Conformational studies of the interdomain linker peptides in the dihydrolipoyl acetyltransferase component of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. AB - Two peptides (PEP1, 26 residues, and PEP2, 22 residues) were synthesized with amino acid sequences identical to two of the long segments of polypeptide chain rich in alanine, proline, and charged amino acids that link the lipoyl domains together in the dihydrolipoyl acetyltransferase component of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. The circular dichroism and 400-MHz 1H NMR spectra of the peptides indicated that they lacked regular secondary structure. Even in the presence of 45% (v/v) hexafluoroisopropanol, they appeared to acquire a helical content of only 23-25%. However, 13C NMR spectroscopy revealed that the Ala-Pro peptide bonds were all (> 95%) in the trans configuration, compared with a value of 87% for the Ala-Pro bond in the model peptide AAPA, which is a recurrent sequence motif in PEP1 and PEP2. Likewise in peptides representing the N- and C-terminal halves of peptide PEP2, the Ala-Pro bonds were again all (> 95%)-trans, suggesting that peptide length is the essential determinant of the cis:trans ratio. Antisera were raised against peptides PEP2 and PEP3, the latter representing a third interdomain segment of polypeptide chain (Radford, S. E., Laue, E. D., Perham, R. N., Martin, S. R., and Appella, E. (1989a) J. Biol. Chem. 264, 767-775). Despite extensive sequence similarity among peptides PEP1, PEP2, and PEP3, only limited immunological cross reactivity was observed, which suggests that the antigenic epitope(s) in the peptides are different and distinct. It is likely that these peptides are representative of a class of inter-domain linkers or spacers found in a wide variety of proteins and endowed with varying degrees of flexibility and stiffness to match their particular biological purpose. PMID- 1429692 TI - Fatty acid ethyl ester synthase in rat adipose tissue and its relationship to carboxylesterase. AB - Fatty acid ethyl ester (FAEE) synthase was obtained from rat adipose tissue in an electrophoretically homogeneous form. The enzyme associated with carboxylesterase activity was purified by acetone precipitation followed by successive chromatographies on DEAE-cellulose, phenyl-Sepharose, and Sephadex G-100 gel. The two activities in rat adipose tissue were associated as judged by their co elution profiles, co-purifications at different steps, co-precipitations by antibody raised against purified FAEE synthase, and identical profiles of inhibition by diisopropyl fluorophosphate. The enzyme catalyzed the hydrolyses of both tri- and monoacylglycerols, and the susceptibilities of substrates increase with decreasing acyl chain length of the fatty acid moiety. Ethyl oleate hydrolyzing activity was about one-eighth of the synthesizing activity. The N terminal amino acid sequence of the first 27 residues of the purified enzyme was identical to that of the carboxylesterase from rat liver. With a polyclonal rabbit antibody against the rat adipose tissue FAEE synthase, the enzyme was demonstrated in the liver, lung, and testis, but not in the kidney. The antibody removed the FAEE-synthesizing activities in adipose tissue (86%), liver (23%), lung (62%), and testis (82%). These results suggest that carboxylesterase contributes to the nonoxidative ethanol metabolism (FAEE synthesis) in various organs. PMID- 1429693 TI - A fluorescently labeled intestinal fatty acid binding protein. Interactions with fatty acids and its use in monitoring free fatty acids. AB - The fatty acid-binding protein from rat intestine (I-FABP) has been covalently modified with the fluorescent compound Acrylodan. Acrylodan was found to label Lys27, one of the few amino acid residues found by x-ray diffraction studies to change orientation upon fatty acid (FA) binding to I-FABP. Binding of FA to this Acrylodan-modified I-FABP (ADIFAB) induces a large shift in fluorescence emission wavelength from 432 to 505 nm. As a consequence, the ratio of emission intensities provides a direct measure of the concentration of FA bound to the protein. Binding of FA is well described by single site equilibrium for FA concentrations below the critical micelle concentration. ADIFAB dissociation constants (Kd) determined at 37 degrees C and at concentrations below the critical micelle concentration for oleate, palmitate, linoleate, arachidonate, and linolenate were, respectively, 0.28, 0.33, 0.97, 1.6, and 2.5 microM. The variation of these Kd values with FA molecular species is highly correlated with the solubility of the FA in water, suggesting that all these FA bind with a similar conformation in the I-FABP binding site. The ADIFAB response together with the measured equilibrium constants allows a direct determination of the concentration of long chain free fatty acid (FFA) in the concentration range, depending upon the FA molecular species, between 1 nM and > 20 microM. As an example of its use as a probe to measure FFA levels, ADIFAB is used here to monitor the time course for FFA release from IgE receptor- and ionomycin activated rat basophilic leukemia (RBL) cells. PMID- 1429694 TI - Regulation of integrin gene expression by substrate adherence. AB - Under substrate adherent conditions, integrin gene expression can be regulated by transforming growth factor-beta, interleukin-1 beta, and prostaglandins. This report demonstrates a new mechanism that can differentially control the expression of several integrins. When MG-63 osteosarcoma cells are maintained in suspension, up-regulation of several integrin alpha-subunits takes place. Within as little as 4 h, the mRNA levels for both the alpha 2- and alpha 4-subunits are increased 4- and 6-fold, respectively. It was found that mRNA levels for the alpha 2-, alpha 4-, and alpha v-subunits were markedly increased in several differentiated cell lines under nonadherent conditions; however, cells that did not express a given integrin under substrate adherent conditions also did not express this integrin when maintained in suspension. The alpha 5-subunit did not upregulate during suspension growth. By immunocytochemistry, changes in integrin mRNA levels were confirmed at the protein level. Both cytochalasin B and a phorbol ester were found to induce the expression of the alpha 2-subunit, but not the alpha 4- and alpha 5-subunits, in a dose-dependent fashion. Many investigators have documented changes in gene expression that result from changes in "cell shape." These phenomena may result from up-regulation of integrin gene expression induced by the lack of substrate adherence. PMID- 1429695 TI - Total metabolic flow of glycosphingolipid biosynthesis is regulated by UDP GlcNAc:lactosylceramide beta 1-->3N-acetylglucosaminyltransferase and CMP NeuAc:lactosylceramide alpha 2-->3 sialyltransferase in human hematopoietic cell line HL-60 during differentiation. AB - We have previously reported that ganglioside GM3 was remarkably increased during monocytoid differentiation of human myelogenous leukemia cell line HL-60 cells and that neolacto series gangliosides (NeuAc-nLc) were enriched during granulocytoid differentiation. In addition, HL-60 was differentiated into monocytic lineage by exogenous GM3 and into granulocytoid by NeuAc-nLc. In the present report, the enzymatic bases of glycosphingolipid biosynthesis in HL-60 during differentiation induced by 12-O-tetradecanoylphorbol-13-acetate and all trans-retinoic acid were investigated. The following results were of particular interest. (i) Lactosylceramide alpha 2-->3 sialyltransferase (GM3 synthase) was remarkably up-regulated during monocyte differentiation, while the GM3 synthase level did not change in granulocytic differentiation. (ii) By contrast, lactosylceramide beta 1-->3N-acetylglucosaminyltransferase (Lc3Cer synthase) was down-regulated during monocytic differentiation, while the activity of Lc3Cer synthase was found to increase in granulocytic differentiation. (iii) The activities of four downstream glycosyltransferases (for synthesis of NeuAc-nLc) were found to increase or to remain unchanged during monocytic and granulocytic differentiation. These results strongly suggested the following. The dramatic GM3 increase and the decrease of NeuAc-nLc during monocytic differentiation are the consequences of the up-regulation of GM3 synthase and the down-regulation of Lc3Cer synthase, although the downstream enzymes are ready to catalyze their enzyme reactions. The notable increase of NeuAc-nLc and the relative decrease of GM3 during granulocytic differentiation are the results of the unchanged level of GM3 synthase and the up-regulation of Lc3Cer synthase together with the activation of the downstream glycosyltransferases. These results suggest that these two key upstream glycosyltransferases, GM3 synthase and Lc3Cer synthase, play critical roles in regulating the glycosphingolipid biosynthesis in HL-60 cells during differentiation. This switching mechanism of these two glycosyltransferases, together with our previous findings, might be one of the most important parts of the determining system of differentiation direction in human myeloid cells into monocytic or granulocytic lineages. PMID- 1429696 TI - Sequence-specific interaction between S1F, a spinach nuclear factor, and a negative cis-element conserved in plastid-related genes. AB - The nuclear gene rps1 coding for the spinach plastid ribosomal protein CS1 exhibits both a constitutive and leaf-specific expression pattern. In contrast to other chloroplast-related genes like rbcS and cab, the leaf induction of rps1 expression is light-independent. These unique features of rps1 expression provide good models to study the mechanisms regulating plastid development and differentiation in higher plants. We report on the identification of a spinach leaf nuclear factor, designated S1F, interacting with the rps1 promoter. The S1F binding site is conserved in the promoter region of many plastid-related genes, including rbcS, cab, and rpl21. A binding activity similar to S1F was detected in nuclear extract from dark-grown de-differentiated soybean suspension cells. Through site-specific mutagenesis and transient expression in soybean cell protoplasts, we show that the S1F binding site is a negative element down regulating the promoter activity of rps1. A ligated tetramer of S1F site was able to repress activity of the cauliflower mosaic virus 35 S promoter extending the negative function of the S1F binding site on promoter activity. PMID- 1429697 TI - Sphingolipids are essential for the growth of Chinese hamster ovary cells. Restoration of the growth of a mutant defective in sphingoid base biosynthesis by exogenous sphingolipids. AB - We previously isolated a temperature-sensitive Chinese hamster ovary cell mutant (strain SPB-1) with thermolabile serine palmitoyltransferase, which is involved in the first step of sphingolipid synthesis (Hanada, K., Nishijima, M., and Akamatsu, Y. (1990) J. Biol. Chem. 265, 22137-22142). In this study, sphingolipid deficient culture medium was used to examine the effect of exogenous sphingolipids on the cell growth of SPB-1. When cultivated in the sphingolipid deficient medium, SPB-1 cells ceased growing at non-permissive temperatures. Under these conditions, de novo sphingolipid synthesis ceased in the SPB-1 cells, resulting in a decrease in levels of sphingomyelin and ganglioside sialyl lactosylceramide (GM3), whereas the parental CHO-K1 cells grew logarithmically with normal sphingolipid synthesis. Exogenous sphingosine restored the contents of both sphingomyelin and GM3 in the SPB-1 cells near to the parental levels through metabolic utilization and allowed the mutant cells to grow even at the non-permissive temperature. Similarly, exogenous sphingomyelin restored the sphingomyelin levels and only partly the GM3 levels and also suppressed the temperature-sensitivity of the SPB-1 cell growth. In contrast, exogenous glucosylceramide, which restored the GM3 levels but not the sphingomyelin levels, failed to suppress the temperature sensitivity of the SPB-1 cell growth. Combination of exogenous sphingomyelin with ceramide, glucosylceramide, GM3, or sphingoid bases did not show any synergistic or additive effect on the SPB-1 cell growth enhancement, compared with sphingomyelin alone. The results indicated that the temperature sensitivity of the SPB-1 cell growth was due to the lack of cellular sphingolipids, possibly that of sphingomyelin. PMID- 1429698 TI - Refinement of the structure of Escherichia coli-derived rat intestinal fatty acid binding protein with bound oleate to 1.75-A resolution. Correlation with the structures of the apoprotein and the protein with bound palmitate. AB - The structure of rat intestinal fatty acid binding protein (I-FABP) with bound oleate (C18:1) has been refined with x-ray diffraction data to a resolution of 1.75 A. The protein contains 10 anti-parallel beta strands composed of 99 residues and 2 short helices of 14 residues. Oleate is located in the interior of the protein in a bent conformation with C1-C12 more ordered than C13-C18. Two of the eight ordered waters in I-FABP:oleate are part of a hydrogen bond network that includes the carboxylate of oleate, the guanidinium group of Arg106, the nitrogen of the indole group of Trp82, and the side chain of Gln115. Most of the methylenes of bound oleate reside in a crevice formed by hydrophobic and aromatic side chains. Tyr70 and Tyr117 envelop the acyl chain from C3 to C8 forming contacts with both the convex and concave faces of its van der Waals surface. The hydroxyls of each phenolic side chain hydrogen bond to ordered water molecules. Two ordered waters make van der Waals contact with the concave face of the bound fatty acid. The omega-terminal methyl of oleate is oriented so that it points toward the center of the benzene of Phe55 allowing it to form van der Waals interactions with its component methylenes. Comparison of the structure of I FABP:oleate with a recently refined 1.19-A model of apoI-FABP and an earlier 2.0 A model of I-FABP:palmitate revealed a remarkable degree of similarity in the positions of their main chain and side chain atoms and in the conformations of the bound oleate and palmitate. The principal differences were confined to a few discrete regions of the protein. The helical domain, the type I turn between beta strands C and D, and the ring of Phe55 together form a solvent-accessible portal to the interior of the protein. They are repositioned in I-FABP:oleate (and I FABP:palmitate) so that the binding cavity is even more accessible to solvent and its volume is increased. The side chain of Phe55 which shows discrete disorder in the apoprotein functions as an omega-terminal "sensing device": moving progressively outward toward the surface as the chain length of the bound fatty acid increases by 2 methylenes. Tyr70 and Tyr117 which also show discrete disorder in the apoprotein structure due to rotation around their C alpha-C beta bonds, are stabilized in a single, well ordered position in the holoproteins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1429699 TI - Feedback inhibition of phosphatidate phosphatase from spinach chloroplast envelope membranes by diacylglycerol. AB - Because the envelope phosphatidate phosphatase plays a pivotal role in chloroplast glycerolipid metabolism, we have analyzed whether diacylglycerol could be a regulatory factor of the enzyme. Using isolated envelope membranes in which the level of diacylglycerol was modified by thermolysin treatment of intact chloroplasts to destroy the galactolipid:galactolipid galactosyltransferase, we have demonstrated that phosphatidate phosphatase activity was reduced when the membrane was enriched in diacylglycerol. All 1,2-diacylglycerol molecular species assayed were demonstrated to inhibit the enzyme to about the same extent. Kinetic studies with envelope from thermolysin-treated chloroplasts were performed in the absence and presence of diacylglycerol, and diacylglycerol was shown to be a powerful competitive inhibitor of the reaction. Finally, using isolated intact spinach chloroplasts, we have demonstrated that in situ phosphatidate phosphatase activity can be modulated by the level of diacylglycerol present in the membrane. The relevance of phosphatidate phosphatase inhibition by diacylglycerol in the regulation of chloroplast glycerolipid biosynthesis is discussed. PMID- 1429700 TI - Inhibition of ascorbic acid transport in human neutrophils by glucose. AB - Because of the structural similarity between glucose and ascorbic acid, we investigated the effect of glucose on uptake and accumulation of ascorbic acid in isolated normal human neutrophils. Ascorbic acid accumulation was determined using high-performance liquid chromatography with coulometric electrochemical detection, in conjunction with liquid scintillation spectrometry. Ascorbic acid accumulation in neutrophils is mediated by a high and a low affinity transport activity. In neutrophils from different volunteers, glucose inhibited uptake and accumulation of ascorbic acid by both transport activities 3-9-fold. The mechanism of inhibition was different for each transport activity: inhibition of the high affinity transport activity was noncompetitive, while inhibition of the low affinity activity was competitive. Glucose-induced inhibition of both ascorbic acid transport activities occurred in neutrophils of all donors tested and was fully reversible. Although the mechanism of ascorbic acid accumulation appeared to be different than that for glucose transport, other monosaccharides and glucose transport inhibitors also inhibited ascorbic acid accumulation. These are the first data to suggest that ascorbic acid accumulation in neutrophils can be regulated by compounds of similar structure. PMID- 1429701 TI - Reducing sugars can induce the oxidative inactivation of rhodanese. AB - The enzyme rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) is inactivated on incubation with reducing sugars such as glucose, mannose, or fructose, but is stable with non-reducing sugars or related polyhydroxy compounds. The enzyme is inactivated with (ES) or without (E) the transferable sulfur atom, although E is considerably more sensitive, and inactivation is accentuated by cyanide. Inactivation of E is accompanied by increased proteolytic susceptibility, a decreased sulfhydryl titer, a red-shift and quenching of the protein fluorescence, and the appearance of hydrophobic surfaces. Superoxide dismutase and/or catalase protect rhodanese. Inactive enzyme can be partially reactivated during assay and almost completely reactivated by incubation with thiosulfate, lauryl maltoside, and 2-mercaptoethanol. These results are similar to those observed when rhodanese is inactivated by hydrogen peroxide. These observations, as well as the cyanide-dependent, oxidative inactivation by phenylglyoxal, are explained by invoking the formation of reactive oxygen species such as superoxide or hydrogen peroxide from autooxidation of alpha-hydroxy carbonyl compounds, which can be facilitated by cyanide. PMID- 1429702 TI - Phospholipase D mimics platelet-derived growth factor as a competence factor in vascular smooth muscle cells. AB - Recent studies have suggested the importance of phosphatidylcholine (PC) metabolism in growth factor-stimulated cells. In these cells, PC is hydrolyzed not only by PC-specific phospholipase C but also by phospholipase D (PLD). In the present investigation, we show that the simple addition of PC-hydrolyzing PLD from Streptomyces chromofuscus to the culture medium of vascular smooth muscle cells elicits choline release into the medium accompanied by the formation of phosphatidic acid. In the presence of ethanol, this treatment elicits a formation of phosphatidylethanol (PEt) at the expense of phosphatidic acid. Furthermore, we show here that exogenous addition of S. chromofuscus PLD induces a marked DNA synthesis in quiescent vascular smooth muscle cells. This DNA synthesis induced by S. chromofuscus PLD is, like platelet-derived growth factor (PDGF)-elicited DNA synthesis, largely dependent on the presence of insulin. In addition, S. chromofuscus PLD-induced PEt formation and DNA synthesis were not affected by protein kinase C down-regulation, whereas PDGF-induced PEt formation and DNA synthesis were significantly inhibited. These observations strongly suggest that protein kinase-dependent activation of PLD is involved in mitogenic signal in PDGF-stimulated cells and that exogenously added PLD acts as a competence factor in the same way as PDGF. PMID- 1429704 TI - The mechanism of ATP inhibition of wild type and mutant phosphofructo-1-kinase from Escherichia coli. AB - Escherichia coli 6-phosphofructo-1-kinase was inhibited by high concentrations of ATP at alkaline pH. The mechanism of the inhibition was studied with two mutants generated by site-directed mutagenesis; I126A, with a Km for fructose-6-P that was more than two orders of magnitude higher than that of wild type but with minimal changes in kcat and Km for ATP, and R72H, with little change in substrate half-saturation concentrations but with a kcat that was 300-fold lower that of wild type enzyme. ATP and fructose-6-P interacted in a mutually antagonistic manner; that is ATP decreased the apparent affinity for fructose-6-P and vice versa. The half-saturation concentrations for both substrates, most strikingly fructose-6-P, increased with increasing pH while the kcat increased. Studies with I126A suggested that ATP inhibition was not dependent on a dissociable group with a pK in the alkaline range and that the inhibition was not caused by abortive binding of substrate to the wrong substrate site. Inhibition was not the result of differential affinity of ATP for the R and T states of the enzyme. The low kcat mutant, R72H, did not display ATP inhibition. These data indicate that ATP inhibition results from substrate antagonism coupled with a steady state random mechanism wherein the high rate of catalysis does not permit equilibration of substrates. PMID- 1429703 TI - Effects of ecotropic murine retroviruses on the dual-function cell surface receptor/basic amino acid transporter. AB - The widely expressed Na(+)-independent transporter for basic amino acids (system y+) is the cell surface receptor (ecoR) for ecotropic host-range mouse retroviruses (murine leukemia viruses (MuLVs)), a class of retroviruses that naturally infects only mice or rats. Accordingly, expression of mouse ecoR cDNA in mink CCL64 fibroblasts yields cells (CEN cells) that have y+ transporter activity above the endogenous background and that bind and are infected by ecotropic MuLVs. The effect of ecotropic MuLV infection on expression of y+ transporter was analyzed in mouse and in mink CEN fibroblasts. Chronic infection with ecotropic MuLVs caused 50-70% loss (down-modulation) of mouse y+ transporter in plasma membranes, detected as a reduced Vmax for uptake and outflow of L [3H]arginine with no effect on Km values. Down-modulation was specific for mouse y+ and did not affect other transporters or the endogenous mink y+, suggesting that it results from specific interaction between mouse y+ and the viral envelope glycoprotein gp70 in the infected cells. Because this partial loss of mouse y+ from cell surfaces is insufficient to explain the complete interference to superinfection that occurs in cells chronically infected with ecotropic MuLVs, alternative explanations for interference are proposed. In contrast to the y+ down-modulation caused by chronic infection, binding of extracellular envelope glycoprotein gp70 at 37 degrees C resulted in noncompetitive inhibition of amino acid import by mouse y+ but had no effect on export through this same transporter or on any transporter properties of mink y+. The effects of gp70 on transport kinetics suggest that it slows the rate-limiting step of the amino acid import cycle, a conformational transition of the empty transporter in which the binding site moves from the inside back to the outside of the cell, and that gp70 has no effect on the rate-limiting step of the amino acid export cycle. Infected cells retain substantial y+ activity. Moreover, the virus binding site on ecoR is in a mobile region that changes conformation during the amino acid transport cycle. PMID- 1429705 TI - Oxidative fragmentation of collagen and prolyl peptide by Cu(II)/H2O2. Conversion of proline residue to 2-pyrrolidone. AB - Oxidative degradation of collagen and the model peptides by Cu(II)/H2O2 has been studied. The depolymerization of collagen was predominantly observed by use of gel filtration chromatography. Polyproline was used as a model for collagen, and the oxidative modification was examined by amino acid analysis. Glutamic acid and gamma-aminobutyric acid were identified in the hydrolysates of oxidized polyproline. The formation of glutamic acid was reduced by treatment with NaBH4. The model peptide, (Pro-Pro-Gly)10, was also degraded by Cu(II)/H2O2, and a new N terminal glycine was generated in proportion to the reaction time. Hydroxyl radical scavengers show only partial inhibition of the degradation of (Pro-Pro Gly)10. In order to estimate the fragmentation mechanism, we used N-tert butoxycarbonyl (Boc)-L-prolylglycine as a model for collagen and (Pro-Pro-Gly)10. The degradation products were isolated and characterized. Then N-tert-Boc-2 pyrrolidone, which provides gamma-aminobutyric acid by acid hydrolysis, was identified. The formation of a 2-pyrrolidone compound from oxidized Boc-L prolylglycine is direct evidence for the scission of the peptide bond. The time dependent formation of N-tert-Boc-2-pyrrolidone and liberation of glycine from N tert-Boc-L-prolylglycine exposed to Cu(II)/H2O2 was observed. These results suggest that the cleavage of the peptide bond (Pro-Gly) was caused by oxidation of the proline residue, which led to the formation of the 2-pyrrolidone compound. We confirmed that proline oxidation leads to the fragmentation of proteins, accompanied by the formation of a 2-pyrrolidone structure. PMID- 1429706 TI - Coagulant properties of hybrid human/porcine factor VIII molecules. AB - Human and porcine factor VIII (fVIII) are activated by thrombin to form a heterotrimer composed of subunits designated A1 and A2 derived from the fVIII heavy chain (HC) and a subunit designated A3-C1-C2 derived from the fVIII light chain (LC). Human and porcine fVIII were activated at the same rate to the same peak levels but dissociation of the A2 subunit and concomitant loss of fVIIIa activity at pH 7.4 and 22 degrees C was 3-fold faster with human fVIIIa compared to porcine fVIIIa (0.35 min-1 versus 0.12 min-1, respectively). To determine structural requirements for the increased activity of porcine fVIII, plasma derived hybrid human/porcine fVIII molecules were isolated. Porcine HC/human LC (pHC/hLC) fVIII had 44-fold higher coagulant activity than reconstituted human fVIII (hHC/hLC), 40-fold higher activity than hHC/pLC, and slightly (1.4-fold) higher activity than reconstituted porcine fVIII (pHC/pLC). Additionally, human and porcine A2 subunits and inactive A1/A3-C1-C2 human and porcine dimers were isolated and reconstitution experiments were done. Addition of the porcine A2 subunit to the human A1/A3-C1-C2 dimer produced coagulant activity similar to that found with porcine fVIIIa and superior to human fVIIIa. These results suggest that human fVIII has weaker coagulant activity than porcine fVIII due to faster dissociation of the A2 subunit and that the A2 subunit itself is responsible for the difference. PMID- 1429707 TI - The 48-kDa subunit of the mammalian oligosaccharyltransferase complex is homologous to the essential yeast protein WBP1. AB - Oligosaccharyltransferase has been purified from canine microsomal membranes as a protein complex with three nonidentical subunits of 66, 63/64, and 48 kDa. The 66 and 63/64-kDa subunits were found to be identical to ribophorins I and II, respectively. The ribophorins are integral membrane glycoproteins that were previously shown to be localized exclusively to the rough endoplasmic reticulum. The 48-kDa subunit (OST48) of the oligosaccharyltransferase complex is not a glycoprotein and is not recognized by antibodies to either ribophorin. Here, we describe the characterization of a cDNA clone that encodes OST48. Like ribophorins I and II, OST48 was found to be an integral membrane protein, with the majority of the polypeptide located within the lumen of the endoplasmic reticulum. OST48 does not show significant amino acid sequence homology to either ribophorin I or II. A 45-kDa integral membrane protein, designated WBP1, from the yeast Saccharomyces cerevisiae was found to be 25% identical in sequence to OST48. Recently, WBP1 was shown to be essential for in vivo and in vitro expression of oligosaccharyltransferase activity in yeast. We conclude that OST48 and WBP1 are homologous gene products. PMID- 1429708 TI - The effects of stem I and loop A on the processing of 5 S rRNA from Drosophila melanogaster. AB - The 135-nucleotide Drosophila melanogaster 5 S RNA precursor is processed by removal of 15 nucleotides from its 3' end before incorporation into the large ribosomal subunit. Mature 5 S RNA consists of five helical stem-loops; stem IV and part of V are dispensable, whereas stem III and the 1/118 G-C base pair closest to the processing site at nucleotide 120 are required for processing (Preiser, P., and Levinger, L. (1991) J. Biol. Chem. 266, 7509-7516; Preiser, P., and Levinger, L. (1991) J. Biol. Chem. 266, 23602-23605). We have investigated the effects of stem I and loop A transversions, transitions, selected additions and deletions on 5 S RNA processing. Stem I single substitutions generally prevent processing, whereas compensatory double substitutions restore a range of processing rates. Proximal to the processing site, stem I double substitutions inhibit processing. In the distal portion of stem I and loop A, the processing effect of paired sequence changes varies widely in an irregular pattern. The 7/112 GU pair and nucleotide 13A least tolerate sequence changes; several mutations clustered close to the stem I-loop A boundary stimulate processing. We interpret these results in terms of the RNA helix path and possible RNA-protein contacts. PMID- 1429709 TI - Manganese(II) oxidation by manganese peroxidase from the basidiomycete Phanerochaete chrysosporium. Kinetic mechanism and role of chelators. AB - Manganese oxidation by manganese peroxidase (MnP) was investigated. Stoichiometric, kinetic, and MnII binding studies demonstrated that MnP has a single manganese binding site near the heme, and two MnIII equivalents are formed at the expense of one H2O2 equivalent. Since each catalytic cycle step is irreversible, the data fit a peroxidase ping-pong mechanism rather than an ordered bi-bi ping-pong mechanism. MnIII-organic acid complexes oxidize terminal phenolic substrates in a second-order reaction. MnIII-lactate and -tartrate also react slowly with H2O2, with third-order kinetics. The latter slow reaction does not interfere with the rapid MnP oxidation of phenols. Oxalate and malonate are the only organic acid chelators secreted by the fungus in significant amounts. No relationship between stimulation of enzyme activity and chelator size was found, suggesting that the substrate is free MnII rather than a MnII-chelator complex. The enzyme competes with chelators for free MnII. Optimal chelators, such as malonate, facilitate MnIII dissociation from the enzyme, stabilize MnIII in aqueous solution, and have a relatively low MnII binding constant. PMID- 1429710 TI - The interaction of human factor VIIa with tissue factor. AB - The interaction of factor VIIa with tissue factor (TF) results in an increase in the catalytic efficiency for the hydrolysis of several synthetic peptidyl p nitroanilide substrates by factor VIIa. The binding of human recombinant factor VIIa to recombinant human TF incorporated into vesicles containing phosphatidylcholine (TF/PC) or phosphatidylcholine/phosphatidylserine (TF/PCPS) was studied using the increased rate of H-D-phenylalanyl L-pipecoyl L-arginine p nitroanilide (S2238) hydrolysis as a signal for the interaction. The saturable dependence of rate on increasing concentrations of factor VIIa or TF/PCPS yielded no obvious evidence for cooperativity and could be analyzed according to the interaction of factor VIIa with independent noninteracting sites (Kd = 259 +/- 60 pM, n = 1.05 +/- 0.12 mol of factor VIIa/mol of TF at saturation). Identical titration curves and equilibrium parameters were derived from titrations using TF/PC or TF in the absence of phospholipids, indicating that possible protein membrane interactions do not further stabilize the extrinsic Xase complex. The dissociation constant for the interaction of factor VIIa with TF/PCPS inferred from measurements of factor X activation (Kd = 197 +/- 38 pM) was comparable with the values obtained from measurements of S2238 hydrolysis. In contrast to the membrane-independent nature of the enzyme-cofactor interaction, the rate of factor X activation was reduced by approximately 50-fold when the enzyme complex was assembled using solution-phase TF. Collectively, the result indicate that the membrane dependence of extrinsic Xase function primarily results from an influence of the membrane surface on factor X utilization. PMID- 1429711 TI - Mutational mapping of the catalytic activities of human tyrosinase. AB - Tyrosinase (EC 1.14.18.1) is a copper-containing metalloglycoprotein that catalyzes several steps in the melanin pigment biosynthetic pathway; the hydroxylation of tyrosine to L-3,4-dihydroxyphenylalanine (dopa) and the subsequent oxidation of dopa to dopaquinone. It has been proposed that tyrosinase is also able to oxidize 5,6-dihydroxyindole (DHI), a later product in the melanogenic pathway, to indole-5,6-quinone. Tyrosinase enzymatic activity is deficient in patients with classic type I oculocutaneous albinism (OCA), and more than 50 distinct mutations have now been identified in the tyrosinase genes of such patients. To determine the effects of the various tyrosinase gene mutations on the catalytic activities of the enzyme, we carried out site-directed mutagenesis of human tyrosinase cDNA, transiently expressed the mutant cDNAs in transfected HeLa cells, and assayed the resultant encoded proteins for tyrosine hydroxylase, dopa, and DHI oxidase activities, and resulting melanin production. The tyrosine hydroxylase activity of normal tyrosinase is thermostable, whereas its dopa oxidase and DHI oxidase activities are temperature-sensitive. Although all amino acid substitutions tested generally affected the dopa oxidase and DHI oxidase activities in parallel, several exerted distinctly different effects on the tyrosine hydroxylase activities. Together, these results confirm the DHI oxidase activity of mammalian tyrosinase and suggest that the dopa oxidase and DHI oxidase activities of tyrosinase share a common catalytic site, whereas the tyrosine hydroxylase catalytic site is at least partially distinct in the tyrosinase polypeptide. PMID- 1429712 TI - Ligand binding characteristics of the major mistletoe lectin. AB - Carbohydrate binding specificity of the galactose-specific, major lectin of mistletoe extract (ML-1) was studied by an inhibition assay using monosaccharides, monosaccharide derivatives, disaccharides, and compounds containing multiple galactosyl terminals. The results indicate that 1) both alpha and beta-galactosyl residues are recognized equally well; 2) each of the hydroxyl groups of galactose contributes to varying degrees to the binding process, the 4-OH being the most important and the 6-OH the least important hydroxyl group; 3) disaccharide sequences of Gal beta 2Gal and Gal beta 3Gal have much higher affinity than galactose, whereas affinity of all other Gal disaccharides is only slightly better than galactose; 4) macromolecular ligands having 10 or more terminal galactosyl residues have 500-fold higher affinity than Gal; and 5) a group on ML-1 with pK alpha of 4.8 appears to be involved in the binding of ligand. PMID- 1429713 TI - Effects of the amino-terminal regions of tropomyosin and troponin T on thin filament assembly. AB - Bacterially expressed alpha-tropomyosin lacks the amino-terminal acetylation present in muscle tropomyosin and binds poorly to actin (Hitchcock-DeGregori, S. E., and Heald, R. W. (1987) J. Biol. Chem. 262, 9730-9735). Using a linear lattice model, we determined the affinity (Ko) of unacetylated tropomyosin or troponin-unacetylated tropomyosin for an isolated site on the actin filament and the fold increase in affinity (y) when binding is to an adjacent site. The absence of tropomyosin acetylation decreased Ko 2 orders of magnitude in the absence of troponin. Tropomyosin acetylation also enhanced troponin-tropomyosin binding to actin, not by increasing cooperativity (y), but rather by increasing Ko. These results suggest that the amino-terminal region of tropomyosin is a crucial actin binding site. Troponin promoted unacetylated tropomyosin binding to actin, increasing Ko more than 1,000-fold. Troponin70-259, which lacks the troponin T peptide (1-69) spanning the overlap between adjacent tropomyosins, behaved similarly to intact troponin. Cooperative interactions between adjacent troponin-tropomyosin complexes remained strong despite the use of a nonpolymerizable tropomyosin and a troponin unable to bridge neighboring tropomyosins physically. The Ko for troponin70-259-unacetylated tropomyosin was 500-fold greater than for troponin159-259-unacetylated tropomyosin, indicating that troponin T residues 70-158 are critical for anchoring troponin-tropomyosin to F-actin. The mechanism of cooperative thin filament assembly is discussed. PMID- 1429714 TI - Isolation and sequencing of cDNAs and genomic DNAs encoding the alpha 4 chain of basement membrane collagen type IV and assignment of the gene to the distal long arm of human chromosome 2. AB - We cloned three overlapping cDNAs covering 2,452 base pairs encoding a new basement membrane collagen chain, alpha 4(IV), from rabbit corneal endothelial cell RNA. Nucleotide sequence analysis demonstrated that the clones encoded a triple-helical domain of 392 1/3 amino acid residues and a carboxyl non-triple helical (NC1) domain of 231 residues. We also isolated a genomic DNA fragment for the human alpha 4(IV) chain, which contained two exons encoding from the carboxyl end of the triple-helical domain to the amino end of the NC1 domain. Identification of the clones was based on the amino acid sequence identity between the cDNA-deduced amino acid sequence and the reported amino acid sequence obtained from a fragment of the alpha 4(IV) collagen polypeptide M28+ (Butkowski, R. J., Shen, G.-Q., Wieslander, J., Michael, A. F., and Fish, A. J. (1990) J. Lab. Clin. Med. 115, 365-373). When compared with four other type IV collagen chains, the NC1 domain contained 12 cysteinyl residues in positions identical to those of the residues in those chains. The domain demonstrated 61, 70, 55, and 60% amino acid similarity with human alpha 1, human alpha 2, bovine alpha 3, and human alpha 5 chains, respectively. The human genomic DNA fragment allowed us to map the alpha 4(IV) gene (COL4A4) to the 2q35-2q37.1 region of the human genome. PMID- 1429715 TI - Expression, purification, and physicochemical characterization of a recombinant Yersinia protein tyrosine phosphatase. AB - The Yersinia protein tyrosine phosphatase (PTPase) Yop51, a C235R point mutation (Yop51*), and a protein lacking the first 162 amino acids at the NH2 terminus (Yop51*delta 162) have been overexpressed in Escherichia coli and purified to homogeneity through the use of CM Sephadex C25 cation exchange chromatography followed by Sephadex G-100 gel filtration. Greater than 50 mg of homogeneous Yop51* and Yop51*delta 162 can be obtained from a single liter of bacterial culture, whereas the same procedure yields only 5 mg of pure Yop51. Large, diffraction-quality crystals have been obtained for Yop51*delta 162. Size exclusion chromatography, sedimentation equilibrium, and enzyme concentration dependence experiments have established that the Yersinia PTPases exist and function as monomers in solution. Yop51 and Yop51* display identical UV, CD, and fluorescence spectra and have identical kinetic and structural stability properties. These full-length Yersinia PTPases have 31% alpha-helix, an emission maximum of 342 nm, a turn-over number of 1200 s-1 at pH 5.0, 30 degrees C, and an unfolding delta G value of 6 kcal/mol at 25 degrees C. Yop51*delta 162 has very similar kinetic and fluorescence characteristics to the full-length molecules, whereas its CD and UV spectra show noticeable differences due to the elimination of 162 NH2-terminal residues. The Yersinia PTPases are by far the most active PTPases known, and their kinetic parameters are extremely sensitive to the ionic strength of reaction medium. PMID- 1429716 TI - In vivo phosphorylation of the yeast uracil permease. AB - The uptake of uracil by the yeast Saccharomyces cerevisiae is mediated by a specific permease encoded by the FUR4 gene. This uracil permease is a multispanning membrane protein that follows the secretory pathway to the plasma membrane. We have used in vivo pulse labeling and immunoprecipitation to show that the uracil permease is phosphorylated. Phosphoamino acid analysis indicates that the phosphorylation occurs on seryl residues. Experiments with temperature sensitive secretory mutants, blocked at successive steps of the secretory pathway, have established that the phosphorylation of the permease takes place at the plasma membrane. Under steady state conditions, Western immunoblotting showed multiple phosphorylated permease species. Their relative abundance appeared susceptible to metabolic conditions. This study is, therefore, a first step toward identifying a molecular mechanism involved in the post-translational control of a yeast transporter. PMID- 1429717 TI - Characterization of the human epidermal profilaggrin gene. Genomic organization and identification of an S-100-like calcium binding domain at the amino terminus. AB - Filaggrin is an intermediate filament-associated protein which functions to aggregate keratin intermediate filaments in the stratum corneum of mammalian epidermis. It is synthesized as a large precursor protein, profilaggrin, that consists of multiple filaggrin units and is localized in keratohyalin granules. In this report, we describe the characterization of cosmid genomic clones containing the human profilaggrin gene coding for 11 complete filaggrin repeats of 324 amino acids each. At the amino- and carboxyl-terminal ends of human profilaggrin are leader and tail peptide sequences of 293 and 157 amino acids, respectively, which differ from filaggrin. The leader peptide is composed of two distinct domains: an 81-residue segment which shows significant homology to the S 100 family of EF hand-containing calcium-binding proteins, and a hydrophilic second domain of 212 residues. The gene is divided into three exons, with one intron (approximately 9.6 kilobase pairs) in the 5' noncoding region and a second one of 570 base pairs between the EF hands. The position of intron 2 is identical to that of other members of the S-100-like family. The presence of an S-100-like domain suggests that profilaggrin binds calcium and that the calcium binding domain is functionally significant in the formation of keratohyalin and/or the subsequent processing of profilaggrin to filaggrin, both of which may be calcium dependent events. PMID- 1429718 TI - Purification, characterization, cloning, and expression of a glutamic acid specific protease from Bacillus licheniformis ATCC 14580. AB - A glutamic acid-specific protease has been purified to homogeneity from Bacillus licheniformis ATCC 14580 utilizing Phe-Leu-D-Glu-OMe-Sepharose affinity chromatography and crystallized. The molecular weight of the protease was estimated to be approximately 25,000 by SDS-polyacrylamide gel electrophoresis. This protease, which we propose to call BLase (glutamic acid-specific protease from B. licheniformis ATCC 14580), was characterized enzymatically. Using human parathyroid hormone (13-34) and p-nitroanilides of peptidyl glutamic acid and aspartic acid, we found a marked difference between BLase and V8 protease, EC 3.4.21.9, although both proteases showed higher reactivity for glutamyl bonds than for aspartyl bonds. Diisopropyl fluorophosphate and benzyloxycarbonyl Leu Glu chloromethyl ketone completely inhibited BLase, whereas EDTA reversibly inactivated the enzyme. The findings clearly indicate that BLase can be classified as a serine protease. To elucidate the complete primary structure and precursor of BLase, its gene was cloned from the genomic DNA of B. licheniformis ATCC 14580, and the nucleotide sequence was determined. Taking the amino-terminal amino acid sequence of the purified BLase into consideration, the clones encode a mature peptide of 222 amino acids, which follows a prepropeptide of 94 residues. The recombinant BLase was expressed in Bacillus subtilis and purified to homogeneity. Its key physical and chemical characteristics were the same as those of the wild-type enzyme. BLase was confirmed to be a protease specific for glutamic acid, and the primary structure deduced from the cDNA sequence was found to be identical with that of a glutamic acid-specific endopeptidase isolated from Alcalase (Svendsen, I., and Breddam, K. (1992) Eur. J. Biochem. 204, 165-171), being different from V8 protease and the Glu-specific protease of Streptomyces griseus which consist of 268 and 188 amino acids, respectively. PMID- 1429719 TI - Progesterone blocks cholesterol translocation from lysosomes. AB - Fluorescent microscopic examination of fibroblasts cultured with low density lipoprotein (LDL) and progesterone (10 micrograms/ml) for 24 h revealed extensive filipin-cholesterol staining of perinuclear lysosomes. Levels of unesterified cholesterol were 2-fold greater than in fibroblasts cultured with LDL alone. Progesterone strongly blocked cholesteryl ester synthesis. When cellular uptake of LDL was monitored in the presence of 58035, a specific inhibitor of acyl CoA:cholesterol acyltransferase, excess unesterified cholesterol was not stored in lysosomes. Discontinuation of LDL uptake in conjunction with progesterone washout markedly reversed the filipin-cholesterol staining of lysosomes. Reversal of the lysosomal cholesterol lipidosis was associated with a rapid burst of cholesteryl ester synthesis and a normalization of the cellular levels of free and esterified cholesterol. In contrast to normal cells, progesterone removal from Niemann-Pick C fibroblasts did not reverse the lysosomal cholesterol accumulation of these mutant cultures. The metabolic precursor of progesterone, pregnenolone, also induced extensive accumulation of cholesterol in lysosomes. Other steroids induced less vacuolar cholesterol accumulation in the following decreasing order: corticosterone and testosterone, promegestone, RU 486. The relative inhibition of cellular cholesterol esterification by the steroids paralleled their respective abilities to sequester cholesterol in lysosomes rather than their inhibition of acyl-CoA:cholesterol acyltransferase activity in cell-free extracts. The progesterone-related inhibition and restoration of lysosomal cholesterol trafficking is a useful experimental means of studying intracellular cholesterol transport. A particularly important feature of its utility is the facile reversibility of the steroid-induced block. The lysosomal cholesterol lipidosis established with a hydrophobic amine, U18666A, was not as readily reversed. PMID- 1429720 TI - Ovarian cancer alpha 1,3-L-fucosyltransferase. Differentiation of distinct catalytic species with the unique substrate, 3'-sulfo-N-acetyllactosamine in conjunction with other synthetic acceptors. AB - Several N-acetyllactosamine (LacNAc) derivatives were tested as acceptors for alpha 1,3-L-fucosyltransferase present in human ovarian cancer sera and ovarian tumor. The enzyme of the soluble fraction of tumor was purified to apparent homogeneity by chromatography on bovine IgG glycopeptide-Sepharose followed by Sephacryl S-200 (M(r) < 67,000). As compared with 2'-methyl LacNAc, 3'-sulfo LacNAc was about 5-fold more sensitive in measuring alpha 1,3-fucosyltransferase in sera (Km, 3'-sulfo LacNAc, 0.12 mM; 2'-methyl LacNAc, 6.67 mM). When ovarian cancer serum was the enzyme source, either the sulfate group or a sialyl moiety at C-3' of LacNAc enhanced the acceptor ability (341 and 242%, respectively), whereas the sulfate group at C-2' or C-6' reduced the activity (22-36%); sulfate at C-6 or fucose at C-2' increased the activity (172 and 253%). The beta benzylation of the reducing end, in general, increased the activity 2-3-fold. The enzyme of the soluble fraction of tumor exhibited more activity toward 3'-sulfo LacNAc (447%), 2'-fucosyl-LacNAc (436%), and 6-sulfo LacNAc (272%). Very low activity was observed with 3'-sialyl LacNAc (12.4%), 2'-sulfo LacNAc (33%), and 6'-sulfo LacNAc (5%); Fuc alpha 1,2Gal beta 1,3GlcNAc beta-O-p-nitrophenyl (166%), 2-methyl Gal beta 1,3GlcNAc beta-O-benzyl (204%), and 3-sulfo Gal beta 1,3GlcNAc (415%) also acted as acceptors, indicating the coexistence of alpha 1,3 and alpha 1,4-fucosyltransferase. The tumor particulate enzyme behaved entirely different, exhibiting low activity with 3'-sulfo LacNAc (39%) and 2'-fucosyl LacNAc (148%); 3'-sialyl, 6'-sulfo, 6-sulfo, or 2'-sulfo LacNAc were 3, 43, 53, and 10% active, respectively. Thus, the ovarian cancer serum alpha 1,3 fucosyltransferase acts equally well on H-type 2,3'-sialyl LacNAc and 3'-sulfo LacNAc, but not on H-type 1. The enzyme of soluble tumor fraction acts on H-type 2,3'-sulfo LacNAc as well as H-type 1 but poorly on 3'-sialyl LacNAc. The tumor particulate enzyme acts on H-type 2 but poorly on 3'-sulfo or 3'-sialyl LacNAc and is inactive with H-type 1. When normal serum was examined with synthetic acceptors, > 80% activity was found as alpha 1,2-fucosyltransferase and the rest as alpha 1,3-fucosyltransferase. A screening of 21 ovarian cancer and 3 normal sera (3'-sulfo LacNAc as acceptor) showed 17-572% increase (average increase, 188%) of alpha 1,3-fucosyltransferase activity in cancer.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1429721 TI - Glucose transporter oligomeric structure determines transporter function. Reversible redox-dependent interconversions of tetrameric and dimeric GLUT1. AB - This study investigates the relationship between human erythrocyte glucose transport protein (GLUT1) oligomeric structure and glucose transporter function. Oligomeric structure was analyzed by hydrodynamic studies of cholate-solubilized GLUT1, by chemical cross-linking studies of membrane-resident GLUT1 and by using conformation-specific antibodies. Transporter function (substrate binding) was analyzed by equilibrium cytochalasin B and D-glucose binding measurements. Erythrocyte-resident glucose transporter is a GLUT1 homotetramer, binds 1 mol of cytochalasin B/2 mol of GLUT1, and presents at least two binding sites to D glucose. Native structure and function appear to be stabilized by intramolecular disulfide bonds and are preserved during GLUT1 purification by the omission of reductant. Native structure is independent of in vitro and in vivo membrane GLUT1 density but is transformed to dimeric GLUT1 by alkaline reduction. Dimeric GLUT1 binds 1 mol of cytochalasin B/mol of GLUT1, presents a single population of binding sites to D-glucose, and is obtained upon GLUT1 purification in the presence of reductant. Native structure and function are restored by treatment of dimeric GLUT1 with glutathione-disulfide (K0.5 glutathione disulfide = 29 microM). We propose that native structure is established prior to transporter translocation to the plasma membrane and that intrasubunit disulfide bonds promote cooperative subunit interactions that stabilize transporter structure and function. PMID- 1429722 TI - Creation of Null/+ mutants of the alpha-tubulin gene in Leishmania enriettii by gene cluster deletion. AB - Tubulins are abundant structural proteins in the Leishmania parasite, and tubulin genes are examples of highly expressed genes, which are present in multiple copies arranged in tandem repeats. Functional analysis of such multicopy genes using genetic manipulation has not yet been possible. Here we describe a method for creating deletions of alpha-tubulin gene clusters by targeted gene replacement and report the isolation of null/+ mutants deleted for either of the two allelic tubulin clusters. We also report null/null mutants in which both clusters have been deleted from their chromosomal loci and in which alpha-tubulin genes are present as episomal elements. Characterization of tubulin mRNA expression in these mutants indicated a posttranscriptional up-regulation of alpha-tubulin mRNA stability in null/+ mutants which contained only one-third the normal number of alpha-tubulin genes. A parallel increase in beta-tubulin mRNA levels indicated coordinate regulation of tubulin mRNA in Leishmania. PMID- 1429723 TI - Differential processing of osteopontin transcripts in rat kidney- and osteoblast derived cell lines. AB - Using immunoprecipitation and tryptic peptide microsequencing we confirmed the identity of normal rat kidney (NRK) cell-secreted 69-kDa major phosphoprotein as osteopontin (OP). We then immunoselected a 1.4-kilobase pair (kb) OP cDNA from a lambda gt11 library prepared from Kirsten sarcoma virus-transformed NRK (KNRK) cellular mRNA, using rabbit anti-69-kDa OP serum. Sequence analysis of this cDNA revealed the presence of a 52-nucleotide-long insert in the 5'-noncoding region, which was absent in OP cDNA cloned from the cDNA library of ROS 17/2.8 rat osteosarcoma cells. The insert sequence is flanked by putative intron splice junctions and is located 15-nucleotide upstream of the translational initiation site. An insert-specific 30-mer oligonucleotide probe hybridized to a single 1.5 kb RNA species from both NRK and KNRK cells, but not from ROS 17/2.8 cells. However, Southern analysis showed the presence of this insert sequence in the genomic DNA of both NRK and ROS 17/2.8 cells. Furthermore, PCR amplification of the insert-containing region using genomic DNAs from both NRK and ROS 17/2.8 cells gave products of identical size and sequence. Since OP is a single copy gene, these data provide strong evidence for differential cell type-specific processing of OP transcripts. In addition, we demonstrate that, in contrast to most transformed cells, levels of OP expression are significantly reduced in KNRK cells as compared to NRK cells. PMID- 1429724 TI - Studies of the catalytic activities and substrate specificities of Saccharomyces cerevisiae myristoyl-coenzyme A: protein N-myristoyltransferase deletion mutants and human/yeast Nmt chimeras in Escherichia coli and S. cerevisiae. AB - Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p) is an essential, 455-residue, monomeric enzyme. Amino- and carboxyl-terminal deletion mutants of Nmt1p were genetically engineered to determine the minimal domain necessary to maintain catalytic activity. Enzyme activity was assessed by (i) sequentially inducing Nmt1p or its mutant derivatives and one of two eukaryotic substrates for the wild type enzyme (S. cerevisiae Gpa1p and rat Go alpha) in Escherichia coli, a bacterium with no endogenous myristoyltransferase activity, and monitoring Nmt-dependent incorporation of exogenous [3H]myristate into the G protein alpha subunits or (ii) an in vitro enzyme assay using lysates prepared from bacteria producing wild type or mutant Nmts. The data indicate that the minimal catalytic domain of Nmt1p is located between Ile59-->Phe96 and Gly451 ->Leu455. Analyses of the ability of mutant nmtps to rescue the lethal phenotype of an nmt1 null allele in a haploid strain of yeast grown on rich media, with or without blockade of cellular fatty acid synthetase, suggest that the amino terminal 59 residues of Nmt1p may play an important noncatalytic role, functioning as a targeting signal so this cytosolic enzyme can access cellular myristoyl-CoA pools generated from activation of exogenous C14:0 by acyl-CoA synthetase(s). Moreover, there appear to be differences in the location or accessibility of myristoyl-CoA pools derived from fatty acid synthetase and acyl CoA synthetases. The E. coli co-expression system was used to map structural elements that determine differences in the peptide substrate specificities of Nmt1p and the orthologous human Nmt. Rat Go alpha is a substrate for both enzymes, whereas human Gz alpha is a substrate only for human NMT. Studies of a series of chimeric enzymes composed of elements from the amino- or carboxyl terminal portions of human and yeast Nmts indicate that (i) recognition/utilization of Gz alpha involves elements distributed from the amino terminal half through the region defined by Leu352-->Lys410 of the 416 residue human enzyme and (ii) formation of a fully functional peptide binding site and a fully functional myristoyl-CoA binding site in either of these enzymes requires contributions from both their amino-terminal and carboxyl-terminal halves. PMID- 1429725 TI - The purification of a human mismatch-binding protein and identification of its associated ATPase and helicase activities. AB - A mismatch-binding protein has been purified an estimated 4500-fold from HeLa nuclear extracts using four different chromatographic steps. Two polypeptides of apparent molecular weight of 160,000 and 100,000 were present in the final affinity-purified fraction as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Partial proteolytic clipping of the protein-DNA complexes visualized after UV treatment indicated that the 100-kDa polypeptide is most likely a degradation product of the 160-kDa polypeptide. UV cross-linking experiments have shown that both these polypeptides bind specifically to oligonucleotide duplexes containing G/T mismatches. Direct DNA binding studies and band-shift competition assays showed that although the mismatch-binding protein binds with highest affinity to oligonucleotides containing G/T mismatches, it is also capable of binding to oligonucleotides containing other mispairs. The purified protein has an associated Mg(2+)-dependent ATPase activity, which is markedly enhanced in the presence of single-stranded DNA. A helicase capable of unwinding a 34-mer oligonucleotide, annealed to a complementary sequence in single-stranded M13, also copurified with the mismatch binding protein. This reaction occurs in an ATP- and magnesium-dependent manner. PMID- 1429726 TI - Isolation of a large aggregating proteoglycan from human brain. AB - A large proteoglycan (365 kDa), identified with monoclonal antibodies raised against chondroitin sulfate, was isolated from human brain. The isolation required anion-exchange chromatography followed by gel filtration through a Sephacryl S-500 column. The proteoglycan bound specifically to [3H]hyaluronate (HA). The binding was not reduced by high salt concentrations (up to 4 M) and was inhibited at low pH (< 4.0). The binding was inhibited by the octamer and decamer (but not the hexamer) oligosaccharides of HA. Limited proteolysis of the proteoglycan gave rise to a relatively stable polypeptide (80 kDa). The amino terminal sequence of the 80-kDa polypeptide was identical to the cDNA-derived amino-terminal sequence of versican, a large human fibroblast proteoglycan. A monoclonal antibody raised against bovine proteoglycans and recognizing the versican core protein reacted by immunoblotting with the proteoglycan isolated from human brain. The antibody was used to localize the proteoglycan in acetone fixed cryostat sections of bovine spinal cord. The localization of the proteoglycan in the central nervous system was identical to that previously reported for glial hyaluronate-binding protein (GHAP), a 60-kDa glycoprotein of the brain extracellular matrix (ECM). However, a major difference was observed with respect to the sensitivity of the two antigens to hyaluronidase. As previously reported, GHAP was released from the tissue by hyaluronidase digestion, whereas the proteoglycan persisted under these conditions. We conclude that the protein-hyaluronate aggregates in brain ECM contain both GHAP and versican, that GHAP is only retained in the ECM by its interaction with hyaluronate, and that the proteoglycan is anchored in some other manner and probably connects cell surfaces with the ECM since it was not released by hyaluronidase digestion. PMID- 1429727 TI - Immunoglobulin kappa gene enhancers synergistically activate gene expression but independently determine chromatin structure. AB - Previous studies have located transcriptional enhancer elements within both the intron and 3'-region of the mouse kappa immunoglobulin gene. Here we address the role of these two enhancers in specifying gene activity and specific chromatin structures. MOPC41 kappa gene constructs, either intact or containing deletions of one or both enhancers, were introduced into S194 mouse plasmacytoma cells for transient and stable expression studies. Transient expression assays revealed that the basal level expression exhibited by enhancerless constructs was activated 100-200-fold by the two enhancers together in a synergistic fashion. A similar trend was observed when both enhancers were present in stably integrated constructs, although the synergy was less pronounced. Analysis of DNase I hypersensitive sites in the chromatin revealed that stably integrated constructs established hypersensitive sites about the enhancer sequences. These sites demonstrated the same nuclease susceptibility as those associated with the endogenous gene(s), and their establishment was independent of the presence of the other enhancer. Thus, although both enhancers are required for maximal gene expression, the elements act independently in determining specific chromatin structures. PMID- 1429729 TI - Protein translocation in the endoplasmic reticulum. Ultraviolet light induces the noncovalent association of nascent peptides with translocon proteins. AB - We have photolyzed cell-free translation systems synthesizing beta-lactamase with 254-nm ultraviolet light. In the presence of canine rough microsomes (RM), incomplete chains of beta-lactamase became enriched relative to the full-length molecule in pellet fractions obtained following photolysis and alkaline carbonate extraction. In addition, high molecular weight aggregates were present on SDS polyacrylamide gels and occurred only when translocation-competent microsomal membranes were used in translation mixtures. The incomplete chains and high molecular weight aggregates were not obtained when RM were inactivated by reaction with N-ethylmaleimide. The incomplete chains did not bind to concanavalin A-Sepharose, indicating that they had not sedimented as a result of being covalently cross-linked to membrane glycoproteins. Both photolysis and alkaline carbonate extraction were required to produce the results. Nascent peptides that were not exposed to alkaline carbonate following photolysis did not appear as high molecular weight bands on SDS-polyacrylamide gels. The high molecular weight aggregates therefore represent denatured protein complexes that contain nascent peptides and microsomal translocon proteins. The results suggest that the translocon is a large proteinaceous complex and that at least a portion of it, when denatured, migrates at a molecular mass of approximately 205 kDa. PMID- 1429728 TI - Identification of basic residues involved in activation and calmodulin binding of rabbit smooth muscle myosin light chain kinase. AB - It is postulated that basic residues in the regulatory region of myosin light chain kinase are important for conferring autoinhibition by binding to the catalytic core. To investigate this proposal, 10 basic amino acids within the regulatory region of rabbit smooth muscle myosin light chain kinase (Lys961 Lys979) were replaced either singularly or in combination with acidic or nonpolar residues by site-directed mutagenesis. All active mutant kinases were dependent on Ca2+/calmodulin for catalytic activity. None of the mutants was active in the absence of Ca2+/calmodulin, suggesting that the autoinhibitory region has not been defined completely. Charge reversal mutants at Arg974, Arg975, and Lys976 resulted in loss of high affinity binding of calmodulin and increased the concentration of calmodulin required for half-maximal activation (KCaM). The charge reversal mutant at Lys979 also increased KCaM but to a lesser extent. Charge reversal mutants at Lys965 and Arg967 resulted in an inactive myosin light chain kinase that could not be proteolytically activated. When these residues were mutated to Ala, the expressed kinase was dependent upon Ca2+/calmodulin for activity and exhibited a decrease in KCaM. Charge reversal mutants in Lys961 and Lys962 also had decreased KCaM values. These basic residues amino-terminal of the calmodulin binding domain may play an important role in the activation of the kinase. PMID- 1429730 TI - The phosphorylation of kinesin regulates its binding to synaptic vesicles. AB - Membrane organella are transported bidirectionally in cells, and the axonal transport system has provided an ideal model system for studying this bidirectional transport. Kinesin and cytoplasmic dynein were identified as candidates for the motor molecules of fast axonal transport, which transport organella along microtubules anterogradely and retrogradely. However, the mechanism that controls this bidirectional transport is unknown. Our previous work revealed that kinesin in axons was associated abundantly with anterogradely transported membranous organella, most of which are believed to be precursors of synaptic vesicles and axonal plasma membranes, while the fractions bound to retrogradely transported ones were very small (Hirokawa, N., Sato-Yoshitake, R., Kobayashi, N., Pfister, K. K., Bloom, G. S., and Brady, S. T. (1991) J. Cell Biol. 114, 295-302). Here we demonstrated in vitro that the binding of kinesin to synaptic vesicles was concentration-dependent and saturable and could be released by high salt concentration. When kinesin was phosphorylated by cAMP-dependent protein kinase, its binding to symaptic vesicles was significantly reduced. By motility assay and by statistical analysis using electron microscopy, we further revealed that synaptic vesicles preincubated with phosphorylated kinesin associated less frequently with microtubules than synaptic vesicles preincubated with unphosphorylated kinesin. The phosphorylation of kinesin should therefore play an essential role in regulating the direction of fast axonal transport by inhibiting its binding to membrane organella, thus releasing it from membrane organella at nerve terminals. PMID- 1429731 TI - The carboxyl terminus of RAP30 is similar in sequence to region 4 of bacterial sigma factors and is required for function. AB - Transcription factor beta gamma (RAP30/74) from rat liver was previously shown in biochemical studies to control the binding of RNA polymerase II to promoters by a mechanism analogous to that utilized by bacterial sigma factors, by decreasing the affinity of polymerase for nonpromoter sites on DNA and by increasing the affinity of the enzyme for the preinitiation complex (Conaway, R. C., Garrett, K. P., Hanley, J. P., and Conaway, J. W. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6205-6209). By constructing and analyzing mutants of beta gamma, we have identified a novel functional domain located in the carboxyl terminus of the gamma (RAP30) subunit. This domain shares sequence similarity with region 4 of bacterial sigma factors; in particular, it exhibits striking similarity to the carboxyl-terminal regions 4.1 and 4.2 of SpoIIIC (Bacillus subtilis sigma k). Evidence from biochemical studies argues that a mutant gamma (RAP30), lacking amino acid sequences similar to sigma homology region 4.2, is able to assemble with the beta (RAP74) subunit to form a mutant beta gamma (RAP30/74) with impaired ability to interact with RNA polymerase II. PMID- 1429732 TI - Alzheimer beta A4-amyloid protein precursor in immunocompetent cells. AB - The mechanism of proteolytic breakdown of the beta A4-amyloid protein precursor (APP) has attracted much attention because of its relevance for Alzheimer's disease. Apart from the pathological role of APP in the amyloidogenesis, many efforts have been made to identify the functional significance of this widely expressed protein in various biological processes. Employing biochemical techniques, we demonstrate that APP is involved in the initiation of the immune response. Upon stimulation, it is expressed by the major functional types of T lymphocytes, i.e. CD4+ and CD8+ cells. As was demonstrated for the CD4+ lymphoid cell line H9, APP is predominantly secreted. The remaining COOH-terminal fragments generated upon secretion were highly unstable. Of the APP produced by immunocompetent cells, considerable amounts were shown to be leukocyte-derived APP (L-APP). In addition, we were able to identify the KPI-containing L-APP isoform, L-APP733, as the major expressed L-APP isoform in immunocompetent cells, including rat microglial cells and astrocytes. The L-APP expression pattern of these cells showed high similarity. These findings seem to be indicative of an important function of APP within the immune system. Therefore, APP may be involved in various immunopathogenic conditions of the periphery and in the central nervous system. PMID- 1429733 TI - Interaction between protein kinase C-dependent and G protein-dependent pathways in the regulation of natural killer cell granule exocytosis. AB - The binding of natural killer (NK) cells to either susceptible tumor cells or antibody-coated targets results in rapid activation of phospholipase C (PLC) in NK cells. PLC activation generates inositol-1,4,5-trisphosphate and sn-1,2 diacylglycerol as second messengers, which, in turn, increase intracellular free calcium concentrations ([Ca2+]i) and protein kinase C (PKC) activity, respectively. These proximal signals initiate a cascade of as yet undefined biochemical events, leading eventually to the exocytosis of preformed cytotoxic granules. To investigate the signal transduction pathways involved in granule exocytosis, we utilized streptolysin-O-permeabilized human NK cells as our experimental model. Our initial studies indicated that the separate activation of either PKC (using the phorbol ester, PMA) or G protein-dependent pathways (using guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S)) stimulated granule exocytosis in a time-, concentration-, and Ca(2+)-dependent manner. PMA-stimulated exocytosis was inhibited by staurosporine or a PKC pseudosubstrate antagonist peptide, but was not affected by GDP. In contrast, GTP gamma S-stimulated exocytosis was effectively inhibited by GDP, but not by staurosporine or the PKC pseudosubstrate antagonist. These observations suggest that NK cell exocytosis can be stimulated by at least two separate pathways; one involving PKC and the other involving a G protein. However, co-stimulation with PMA and GTP gamma S synergistically enhanced exocytosis, suggesting that even though the two exocytotic pathways were biochemically distinct, cross-talk between the two pathways may potently influence the exocytotic process. These results define a regulatory role for PKC- and G protein-dependent pathways during granule exocytosis from NK cells. PMID- 1429734 TI - A key role for a 145-kDa cytosolic protein in the stimulation of Ca(2+)-dependent secretion by protein kinase C. AB - Cytoplasmic Ca2+ is a major regulator of exocytosis in secretory cells; however, the Ca(2+)-dependent mechanisms that trigger secretion have not been elucidated. Protein kinase C (PKC) has been proposed to be an important Ca(2+)-dependent component of this regulation; however, the effects of this enzyme on the exocytotic apparatus have not been identified. We developed a PKC-deficient, semi intact PC12 cell system in which direct stimulatory effects of purified PKC on Ca(2+)-dependent norepinephrine secretion were studied. The reconstitution of optimal Ca(2+)-activated norepinephrine secretion by semi-intact PC12 cells required the addition of MgATP and cytosolic proteins. PKC-deficient cytosol exhibited reduced reconstituting activity that was fully restored by the addition of purified PKC. The restoration of Ca(2+)-dependent norepinephrine secretion by PKC required the presence of other proteins in the cytosol, in particular, a high molecular weight protein. The high molecular weight protein was identified as p145, a recently characterized 145-kDa brain protein. The addition of PKC enhanced phosphorylation of p145 under conditions of fully reconstituted Ca(2+) activated norepinephrine secretion. The results indicate that 1) PKC is neither necessary nor sufficient for Ca(2+)-activated secretion, whereas other cytosolic proteins are required; and 2) the stimulation of Ca(2+)-activated secretion by PKC is dependent upon cytosolic proteins such as p145 and may be largely mediated through the phosphorylation of p145. PMID- 1429735 TI - Vitamin A is a key regulator for cell growth, cytokine production, and differentiation in normal B cells. AB - In the present paper we demonstrate that retinol-retinol-binding protein and chylomicron remnant retinyl esters in concentrations normally found in human plasma inhibit growth of normal human B lymphocytes. Physiological concentrations of retinoic acid (about 30 nM) were less active than physiological concentrations of retinol (about 3 microM). Pharmacological concentrations of retinol and retinoic acid were more active than the concentrations normally found in plasma. Retinol (3 microM) inhibited anti-IgM-mediated DNA synthesis as measured by [3H]thymidine uptake at 72 h by 78%. Furthermore, we found that the cells were blocked in the mid-G1 phase of the cell cycle. Thus, neither MYC up-regulation measured at 3 h nor the expression of the early activation antigen 4F2 was reduced by retinol, whereas the late activation markers (transferrin receptor expression and actinomycin D staining at 48 h of stimulation) were markedly inhibited. Retinol reduced the interleukin 6 production induced by anti-IgM and interleukin 4 after 48 h, whereas the induction of interleukin 6 and tumor necrosis factor by O-tetradecanoylphorbol-13-acetate and ionomycin was less affected. We also noted that the retinoids reduced the formation of plaque forming cells (i.e. Ig synthesis). These data imply that vitamin A present in human plasma is a normal modulator of B cell function. PMID- 1429736 TI - Structure and expression of the Kas12 gene encoding a beta-ketoacyl-acyl carrier protein synthase I isozyme from barley. AB - The beta-ketoacyl-acyl carrier protein (ACP) synthase I in the plant fatty acid synthetase catalyzes the condensations of acetate units to a growing acyl-ACP leading to the synthesis of palmitoyl-ACP. Barley chloroplasts contain three cerulenin sensitive beta-ketoacyl-ACP synthase I isoforms, alpha 2, alpha beta, and beta 2. The Kas12 gene encoding the beta 2 isozyme has been isolated and sequenced. The gene spans 3.8 kilobases and contains seven exons separated by six intervening sequences varying from 75 to 1008 base pairs in length. The mosaic gene structure is different compared with that of the beta-ketoacyl synthase in the multifunctional rat and goose fatty acid synthetases. Southern blot analyses of genomic DNA from barley, wheat, and the barley-wheat chromosome addition lines indicate that Kas12 is a single copy gene located on chromosome 2. Primer extension analyses identified four transcription start sites located 168-171 nucleotides upstream from the translation initiation codon. The Kas12 promoter lacks an appropriately positioned TATA box and contains a GC-rich region including two GC elements similar to the Sp1 transcription factor-binding site. In this regard Kas12 closely resembles a set of ubiquitously expressed eucaryotic genes. In accord with this deduction, polymerase chain reaction analysis showed that the Kas12 transcript is present in barley roots, germinating embryos, developing kernels, and leaves. PMID- 1429737 TI - Electrophoretic studies on the assembly of the nitrogenase molybdenum-iron protein from the Klebsiella pneumoniae nifD and nifK gene products. AB - The electrophoretic properties of the molybdenum-iron (MoFe) protein component of nitrogenase and an iron-molybdenum cofactor (FeMoco)-reactivatable apoMoFe protein from Klebsiella pneumoniae were examined under anaerobic ([O2] < 5 ppm), nondenaturing conditions. In wild type K. pneumoniae extracts, two immunoreactive species migrating more slowly than purified MoFe protein were detected using anti MoFe protein antibodies. The uppermost species comigrates with the apoMoFe protein produced by a K. pneumoniae mutant unable to synthesize FeMoco (UN106) and by Escherichia coli harboring the plasmids pVL222+pVL15 (nifHDKTYUSWZM+A). In vitro FeMoco titration of the UN106 and pVL222+pVL15 extracts increases the electrophoretic mobility of the apoMoFe protein to that of purified MoFe protein in a two-step process giving rise to a species of intermediate mobility between the apo- and holoMoFe proteins. Two-dimensional gel electrophoresis showed that a 20-kDa peptide is associated with the apoMoFe protein and with the intermediate species, but not with the holoMoFe protein. N-terminal sequencing identified this associated peptide as the nifY gene product, which we propose is acting as a temporary enforcer of the apoMoFe protein structure required for cofactor binding that is released upon FeMoco activation. This FeMoco-induced mobility shift was used to characterize the mutant apoMoFe proteins produced in E. coli as a result of deleting the various nitrogen fixation (nif) genes from the plasmid pVL222. E. coli extracts bearing plasmids deleted in nifH, nifS, nifTYUM, or nifWZM exhibit less than 10% of the apoMoFe protein activity of derepressed UN106 and contain an immunoreactive species whose electrophoretic mobility is increased upon addition of FeMoco from that of apoMoFe protein to that of holoMoFe protein in a single step. Anaerobic nondenaturing gel electrophoresis of 55Fe-labeled E. coli extracts followed by autoradiography showed that these inactive apoMoFe species do not contain iron, indicating that the P-clusters are absent. We therefore propose that NifH, S, U, W, Z, and M are all involved, to varying degrees, in P cluster assembly. In addition, the presence of the P-clusters does appear to be necessary for the two-step FeMoco activation of the apoMoFe protein to occur. PMID- 1429738 TI - Pseudomonas exotoxin A-epidermal growth factor (EGF) mutant chimeric protein as an indicator for identifying amino acid residues important in EGF-receptor interaction. AB - Epidermal growth factor (EGF) was fused to the carboxyl end of a modified pseudomonas exotoxin A that has its toxin binding domain deleted. This chimeric toxin designated as PE(delta Ia)-EGF kills A431 cells through the EGF receptor mediated pathway. In this study, we used a random mutagenesis approach to make point mutations on EGF, followed by replacing the wild type EGF in PE(delta Ia) EGF with these EGF mutants. We have constructed 14 different PE(delta Ia) EGFmutants, and examined their EGF receptor binding activity as well as their cytotoxicity to A431 cells. Our results showed that individual mutations of Val19 to Glu and Val34 to Asp in the EGF domain of PE(delta Ia)-EGFmutants resulted in an increase in the binding affinity to EGF receptor and cytotoxicity to A431 cells. On the other hand, individual mutations of His16 to Asp and Gly18 to Ala in the EGF domain of PE(delta Ia)-EGFmutants lead to a decrease in the binding affinity to EGF receptor and cytotoxicity to A431 cells. In addition, mutations of any of the cysteine residues of EGF in PE(delta Ia)-EGFmutants resulted in the loss of their binding activity to EGF receptor and a corresponding loss of their cytotoxicity. This study indicates that the cytotoxicity of PE(delta Ia) EGFmutant to EGF receptor-bearing cells may be used as an indicator to screen mutations of EGF important in EGF-receptor interactions. PMID- 1429739 TI - Purification and activation of brain sulfotransferase. AB - Galactosylceramide sulfotransferase (EC 2.8.2.11) catalyzes the biosynthesis of sulfatide from galactocerebroside and adenosine 3'-phosphate 5'-phosphosulfate (PAPS). This enzyme is developmentally controlled, reaching a maximum activity in the brains of mice corresponding to that of maximum myelination. The product, sulfatide, is an important component of myelin. This transferase from mouse brain has been purified 2600-fold using a combination of pyridoxal 5'-phosphate- and ATP-ligated columns. The purified enzyme yielded a single band following SDS polyacrylamide gel electrophoresis with an apparent M(r) of 31,000. The entire purification procedure can be completed in 1 day. The pH optimum for the enzyme is 7.0. The Km for PAPS is 1.2 x 10(-6) M, and the Km for cerebroside is 2.6 x 10(-5) M. Cerebroside concentrations > 80 pmol/ml are inhibitory. Enzyme preparations were associated with several lipids. Vitamin K+P(i) activated purified preparations of the sulfotransferase and maintained enzyme activity during storage at -80 degrees C. PMID- 1429740 TI - Structure of the gene encoding dihydrolipoyl transacylase (E2) component of human branched chain alpha-keto acid dehydrogenase complex and characterization of an E2 pseudogene. AB - We have determined the structural organization of the dihydrolipoyl transacylase (E2) gene of the human branched chain alpha-keto acid dehydrogenase complex. The single copy E2 gene spans approximately 68 kilobases of genomic DNA. The complete coding region consisting of the 5'- and 3'-untranslated regions, the mitochondrial targeting sequence (61 amino acids), and the mature E2 sequence (421 amino acids) are encoded by 11 exons ranging from 62 to 2239 base pairs. All the donor and acceptor splice sites conform to the gt-ag rule. Sequence analysis of the promoter-regulatory region showed the presence of a "CAAT box"-like sequence 537 bases upstream of the transcription initiation site. The "TATA box" like sequence is absent. Also located in this region are sequences resembling glucocorticoid-responsive and cAMP-responsive elements, fat-specific elements, and Sp1- and AP-2-binding sites. Several sets of direct and inverted repeats are also present. Promoter assays using human hepatoma cells (Hep-G2) and Swiss mouse preadipocytes (3T3-L1) showed that a 4.1-kilobase PstI fragment upstream of the transcription start site confers high expression of the luciferase reporter gene. Moreover, an intronless E2 pseudogene was isolated. It corresponds to the complete mitochondrial presequence and the lipoyl-bearing domain that are encoded by exons I through IV of the functional E2 gene. However, the E2 pseudogene contains multiple base changes, deletions, and insertions, and is flanked by short direct repeats. The data indicate that the E2 pseudogene is a retroposon. PMID- 1429741 TI - Purification of Limulus polyphemus proclotting enzyme. AB - Horseshoe crabs (Limulus polyphemus and Tachypleus tridentatus) possess a proteolytic blood coagulation system within their amebocytes that, after release and endotoxin activation, generates a polymerized insoluble coagulin clot. Clotting enzyme from horseshoe crab amebocyte lysate is the protease that activates the clottable protein (coagulogen) which then forms the coagulin clot. Comparison of the previously published descriptions of this enzyme has revealed significantly discordant biochemical characteristics. We purified a 60-kDa proclotting enzyme from L. polyphemus amebocyte lysate to a single band on polyacrylamide gel electrophoresis. After electrophoresis, evaluation of enzymatic activity of this protein within gels demonstrated that the band of purified protein corresponded to enzymatic activity, as detected by amidolytic activity for chromogenic substrates and by gelation of coagulogen applied to the gel. The enzymatic activity was inhibited by serine protease inhibitors. The purified proclotting enzyme had a molecular weight and amino acid composition different from the previously published characterizations of proclotting enzymes from both L. polyphemus and T. tridentatus. PMID- 1429742 TI - Deletion of the pro-alpha 1(I) N-propeptide affects secretion of type I collagen in Chinese hamster lung cells but not in Mov-13 mouse cells. AB - We have introduced two mutations into a full-length human pro-alpha 1(I) cDNA that delete 114 amino acids or the entire 139 amino acids of the N-propeptide domain. Wild-type and mutated versions of the cDNA were introduced into cultured Chinese hamster lung (CHL) cells, which do not produce endogenous type I collagen, and into Mov-13 mouse cells, which produce endogenous pro-alpha 2(I) chains but not pro-alpha 1(I) chains. As judged by resistance to proteases, neither mutation impaired intracellular triple helical assembly of human alpha 1(I) homotrimers in CHL cells, or of chimeric type I collagen comprised of human alpha 1(I) and mouse alpha 2(I) chains in Mov-13 cells. Thus, the N-propeptide is not necessary for intracellular assembly of the main helical collagen domain of type I collagen. In CHL cells the rate of secretion of the mutant homotrimers was greatly reduced as compared to wild type homotrimers, and by immunofluorescence and immunoelectron microscopy, the mutant chains were shown to be accumulated in large vesicular expansions of the rough endoplasmic reticulum. When such cells were retransfected with cDNA encoding wild-type human alpha 2(I) chains, mutant alpha 1(I) chains were not rescued and heterotrimers containing the mutant chains were also retained in the intracellular vesicles. By contrast, deletion of the N propeptide did not affect secretion of heterotrimers containing mutant chains from Mov-13 cells. Thus, an intact N-propeptide appears necessary for efficient secretion of type I collagen from some but not all cell types. PMID- 1429743 TI - Effects of folate receptor expression following stable transfection into wild type and methotrexate transport-deficient ZR-75-1 human breast cancer cells. AB - Two biochemically distinct systems, the high affinity folate receptor and the lower affinity reduced-folate carrier, have each been implicated in mediating the transport of folates and antifolates into cells. Previous studies from our laboratory have shown that methotrexate accumulation into wild type (WT) ZR-75-1 human breast cancer cells involves a system with characteristics of the reduced folate carrier, that this system is deficient in methotrexate resistant (MTXR) ZR 75-1 cells in which methotrexate transport is undetectable and that neither breast cancer cell line expresses folate receptors. In this report we examined the possible interaction of the reduced-folate carrier with folate receptors by stably transfecting both WT ZR-75-1 and MTXR ZR-75-1 cells with an expression vector containing a folate receptor cDNA. Clones of stably transfected MTXR ZR-75 1 and WT ZR-75-1 cells expressing comparable levels of folate receptors were studied and compared to the nontransfected cell lines. Although nontransfected WT and MTXR ZR-75-1 cell lines require concentrations > or = 100 nM folic acid for growth, the expression of folate receptors in transfected WT and MTXR ZR-75-1 cells permitted the growth of both cell lines in low concentrations (1 nM) of folic acid. While the defect in the reduced-folate carrier system in MTXR ZR-75-1 cells inhibits their growth in medium containing low concentrations of folinic acid (< or = 1 microM), MTXR ZR-75-1 cells expressing folate receptors display uninhibited growth in 1 nM folinic acid. The accumulation of folic acid, folinic acid, and methotrexate is enhanced in folate receptor-transfected WT ZR-75-1 cells and MTXR ZR-75-1 cells. Furthermore, the accumulation of folates and antifolate was similar in both transfected WT and MTXR ZR-75-1 cell lines that expressed folate receptors. This suggests that alterations in the reduced-folate carrier do not affect folate receptor function. We also examined the effect of folate receptor expression on the sensitivity of WT and MTXR ZR-75-1 cells to methotrexate and to the lipophillic antifolate trimetrexate. Increased folate receptor expression decreased the sensitivity of WT ZR-75-1 cells toward the antifolate trimetrexate, presumably through increased uptake of reduced folates. Although the expression of the folate receptor enhanced the growth of both cell lines in low folate concentrations, it did not affect the sensitivity of either WT or MTXR ZR-75-1 cells to methotrexate. PMID- 1429744 TI - Structure of triphosphonoglycosphingolipid containing N-acetylgalactosamine 6-O-2 aminoethylphosphonate in the nervous system of Aplysia kurodai. PMID- 1429745 TI - Agonist action of indole derivatives at 5-HT1-like, 5-HT3, and 5HT4 receptors in vitro. AB - 1. The potency of indole analogues has been studied, in vitro, at 5 hydroxytryptamine4 (5-HT4) receptors mediating contractions of guinea-pig ileum and relaxation of rat oesophagus. These have been compared to other 5-HT receptors in canine saphenous vein (5-HT1-like), rabbit aorta (5-HT2), and guinea pig ileum (5-HT3). 2. At receptors mediating 5-HT4 responses in ileum and oesophagus, the rank orders of potency were similar. These rank orders differed from those observed at 5-HT1-like, 5-HT2, and 5-HT3 receptors. In particular, 5 hydroxy N,N, dimethyltryptamine but not 5-methoxy N,N, dimethyltryptamine acted as agonists at 5-HT4 receptors. At 5-HT1-like, 5-HT2 and 5-HT3 receptors these compounds were both active. 3. The 5-HT receptors mediating contractions of canine cephalic vein exhibited a rank order profile similar to that observed at receptors mediating contractions of canine saphenous vein, suggesting stimulation of a 5-HT1-like receptor. 4. The rank order of potency of the substituted indoles differed at 5-HT receptors mediating responses in canine saphenous vein, rabbit aorta and guinea-pig ileum (determined in the presence of 5-methoxytryptamine to desensitize 5-HT4 receptors), suggesting the presence of three distinct receptors. Indeed, at 5-HT3 receptors in the ileum, only three agonists (5-HT, 2 methyl-5-HT and 5-hydroxy N,N, dimethyltryptamine) elicited a response, while all remaining compounds were inactive. 5. It is concluded that rank orders of indole potency can prove useful in the delineation of 5-HT subtypes and together with differential antagonist affinities support the existence of four 5-HT receptor subtypes. PMID- 1429746 TI - Gangliosides prevent the dimethyl sulphoxide-induced increases in [3H] noradrenaline release from rat isolated atria. AB - 1. In the rat isolated atria labelled with [3H]-noradrenaline ([3H]-NA), the exposure to 1-4% v/v dimethyl sulphoxide (DMSO) during 15 min caused a concentration-dependent increase in the spontaneous outflow of tritiated products, which reached up to 50% with 2% DMSO and up to 100% with 4% DMSO. These effects were entirely prevented by a 2 h in vitro pretreatment with 50 microM bovine brain gangliosides mixture (BBG). 2. The pattern of the spontaneous release of tritiated products was 17.5 +/- 1.9% of [3H]-NA; 38.7 +/- 2.1% of [3H] 3,4-dihydroxyphenylglycol ([3H]-DOPEG); 36.1 +/- 2.4% of [3H]-O-methylated deaminated metabolites ([3H]-OMDA); 4.7 +/- 0.9% of [3H]-3,4-dihydroxymandelic acid ([3H]-DOMA) and 2.9 +/- 0.2% of [3H]-NMN. After 10 min exposure to 2% DMSO, the increase in basal outflow by this agent consisted of 7.4 +/- 2.5% [3H]-NA and 89.0 +/- 3.6% [3H]-DOPEG. The 2 h preincubation with 50 microM BBG protected from the increase of total radioactivity and also from the metabolic alterations caused by DMSO. The BBG per se did not modify either the basal efflux or the metabolic fate of the [3H]-transmitter. 3. In addition to enhancing the spontaneous outflow of radioactivity, the exposure to 2% v/v DMSO increased by 400% the overflow of the [3H]-transmitter elicited by nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429747 TI - Contribution of vagal blockade to the tachycardia induced by the antimuscarinic agents atropine and pirenzepine. AB - 1. The cardiac cholinergic blockade and the chronotropic effect of the widely differing antimuscarinic drugs atropine and pirenzepine were investigated in the dog. 2. In conscious dogs, suppression of the parasympathetic system with atropine (0.2 mg kg-1 h-1) causes marked brief cardioacceleration (234 +/- 13 beats min-1) while pirenzepine (3 mg kg-1 h-1) causes moderate but persistent cardioacceleration (179 +/- 13 beats min-1). After suppression of the influence of the cardiac sympathetic system these cardioaccelerator effects are attenuated, particularly those of pirenzepine. 3. The effects of vagal stimulation are blocked completely and persistently by both agents. 4. When the cardioinhibitory action of the vagus nerve is blocked by pirenzepine the induced tachycardia can be increased by atropine, which causes an additional cardioacceleration (25 +/- 9 beats min-1). 5. These results show that the tachycardia induced by antimuscarinic agents is not only due to vagal blockade. The different mechanisms which may be involved are discussed. The results suggest that pirenzepine can suppress cholinergic influence on the heart more electively than atropine, which induced an 'excess tachycardia'. Also, intrinsic heart rate can be approached more closely when pirenzepine is used to suppress the parasympathetic system, than with atropine. PMID- 1429748 TI - Influence of the substrate binding characteristics of fibronectin on corneal epithelial cell outgrowth. Student Research Award in the Doctoral Degree Candidate Category, Fourth World Biomaterials Congress (18th annual meeting of the Society for Biomaterials), Berlin, Germany, April 24-28, 1992. AB - The outgrowth of corneal epithelial cells onto a polymeric substrate is expected to be the primary event in the epithelialization of a synthetic corneal graft. Circular corneal buttons (5 mm) were punched from excised rabbit corneas and placed onto bare substrates or substrates preadsorbed with fibronectin (fn), albumin, or binary mixtures of both fn and albumin. Cell outgrowth areas were measured after culturing the buttons for 4 days in serum-free medium. Fibronectin adsorption to the materials was measured from pure and binary solutions with 125I radiolabeled fibronectin. A parameter thought to be related to the binding strength of fn to polymeric substrates was measured in parallel experiments by partial elution of the adsorbed fn by 3% sodium dodecyl sulfate (SDS). Following pure solution fibronectin adsorption a range of outgrowth areas was measured (from 0.86 +/- 0.03 cm2 for glass to 1.49 +/- 0.03 cm2 for TCPS). On all of the materials tested cell outgrowth areas increased following fn preadsorption and decreased following albumin preadsorption relative to bare surfaces (p less than 0.05). Following preadsorption with binary protein mixtures cell outgrowth areas increased with fibronectin adsorption, however, the outgrowth areas were not determined solely by the concentration of fn adsorbed onto the surfaces. This result suggested that the biological efficiency of the adsorbed fibronectin was substrate-dependent. When the cell outgrowth data were cross-plotted against fn retention following SDS elution, the outgrowth areas were found to increase along with increases in fn retention. Based on these data we suggest that epithelial cell outgrowth may be partially governed by the tightness of binding between the fn molecules and the underlying substrate. PMID- 1429749 TI - In vitro synergistic, antagonistic, and duration of exposure effects of metal cations on eukaryotic cells. AB - Effects of duration of exposure of single metal cations (Ag+1, Cd+2, Cu+2, Ga+3, Ni+2, and Zn+2) on 3H-thymidine (3H-Tdr) incorporation and 3-[4,5-dimethyl thiazol-2yl-]-2,5-diphenyl tetrazolium bromide-formazan (MTT-f) production in cultured murine fibroblasts (Balb/c 3T3) were investigated, and the synergistic and antagonistic effects of two metal cations applied simultaneously to the fibroblasts were assessed. The effects of duration of exposure were quantified using TC50 values (concentration of an element required to cause 50% toxicity compared with controls) measured after 24, 48, or 72 h. Using MTT-f production, Cd+2, Cu+2, Ga+3, and Ni+2 showed significantly lower TC50 values with increasing time of exposure, whereas the TC50 values for Ag+1 and Zn+2 remained constant. The TC50 values using 3H-Tdr incorporation exhibited a similar pattern with time of exposure, but the effects were less pronounced. The TC50 values for 3H-Tdr and MTT-f tended to equalize at 72 h. All combinations of cations tested (Ag-Cu, Ag Zn, Ag-Ni, Cu-Zn, Cu-Ni, Ga-Ni, and Cu-Cd) exhibited synergistic and antagonistic effects as measured by MTT-f production. Synergistic and antagonistic effects were not necessarily mutually exclusive in the same system. PMID- 1429750 TI - Effect of surface processing on the attachment, orientation, and proliferation of human gingival fibroblasts on titanium. AB - The adhesion, orientation, and proliferation of human gingival fibroblasts was studied on electropolished (elpTi), etched (etchTi), and sandblasted (sblTi) titanium surfaces. The texture, chemical state, and composition of the titanium surfaces were analyzed using a surface tracing instrument and electron spectroscopy for chemical analysis. Considerable differences were evident in the surface texture and chemical composition of the differently treated titanium plates. Electropolishing produced the smoothest and cleanest surface. Human gingival fibroblasts attached, spread, and proliferated on all titanium surfaces. However, cells on elpTi exhibited an extremely flat morphology and seemed to form cellular bridges with adjacent cells, whereas the etchTi and sblTi surfaces harbored both round and flat cells with many long processes. Cells on elpTi appeared to grow in thick layers with no specific orientation, whereas on etchTi surfaces they were migrating along the parallel, irregular minor grooves caused by mechanical polishing, and on sblTi surfaces they seemed to grow in clusters. Stress-fiber type actin bundles and vinculin-containing focal adhesions were present in cells spreading on elpTi and etchTi surfaces but not in cells spreading on sblTi surfaces. Cell shape, orientation, and proliferation appear to depend on the texture of the titanium surface and probably also on the properties of the oxide layer and adjacent bulk material. Our findings suggest that smooth or finely grooved titanium surfaces could be optimal in implants adjacent to soft tissues as they support the attachment and growth of human gingival fibroblasts. PMID- 1429751 TI - Cell-type-specific adhesion mechanisms mediated by fibronectin adsorbed to chemically derivatized substrata. AB - Plasma fibronectin (pFN) adhesion mechanisms on inert substrata were evaluated for murine fibroblasts (3T3) and human neuroblastoma (Platt) cells using glass coverslips chemically derivatized with a self-assembled monolayer of aliphatic chains terminated with a specific endgroup to interact with adsorbed pFN: [CH3], [SH], [SCOCH3], [NH2], [SO3H], or underivatized glass [SiOH]. All surfaces bound similar amounts of pFN and facilitated attachment of both cell types within narrow ranges. However, spreading/differentiation responses of cells differed considerably among the surfaces. While 3T3 cells spread and developed microfilament stress fibers comparably on all surfaces, inclusion of an RGDS containing synthetic peptide in the medium revealed variation in resistance to stress fiber formation mediated by an RGDS-recognizing integrin: [NH2] greater than [CH3] much greater than [SiOH],[SH],[SCOCH3]. Different patterns of neurite formation were observed for neuroblastoma cells: [SiOH], [SO3H] greater than [SCOCH3],[SH] much greater than [CH3] greater than [NH2]. Similarity in cell responses to both [CH3] and [NH2] surfaces argues against a pattern dependent upon the hydrophobicity of substrata. When pFN was diluted to a subsaturable concentration with albumin for adsorption, neuroblastoma responses changed significantly from those observed on pFN-saturated surfaces, for both spreading and neurite generation: [NH2],[SO3H] much greater than [SH], [SCOCH3] greater than [SiOH],[CH3]. Responses to the pFN: albumin mixture were markedly improved from responses after sequential adsorptions, demonstrating "optimization" of pFN conformation (not merely binding) by coadsorption of albumin molecules. In most cases, the [NH2] surface yielded responses distinctively different from the other surfaces. Overall, these data suggest many variations in the conformation of pFN molecules adsorbed to specific inert surfaces, as well as variations in the responses of cell surface receptors to conformationally specific pFNs. They also reveal cell-type-specific changes in differentiated cell responses on derivatized substrata, mediated by different classes of cell surface receptors for the two cell types, and provide optimism for regulating FN-dependent adhesion mechanisms in either positive or negative contexts on biomaterial surfaces derivatized with one or more of these chemical end-groups. PMID- 1429752 TI - Polypropylene small-diameter vascular grafts. AB - Polypropylene's physical properties (e.g., high tensile strength) and relatively inert behavior suggest that fabrication into an arterial substitute may result in an efficacious prosthesis. Grafts were woven from polypropylene yarn into conduits 4 mm I.D. x 50 mm in length. Control grafts were Dacron and ePTFE. Baseline platelet aggregometry on all dogs was performed with 10(-5) M ADP. Aspirin and dipyridamole were given for three days preoperatively and maintained for 2 weeks after surgery. Fifty-four grafts were placed into the aortoiliac position, two different graft materials per dog. The grafts were explanted at intervals of 2 weeks through 16 months; photographed for thrombus-free surface area determinations; and preserved for light, scanning, and transmission electron microscopy. Late (4-16 month) patency was 81% (13/16) for polypropylene, 69% (9/13) for Dacron, and 20% (1/5) for ePTFE. These data include one year patencies of 11/12 (92%) for polypropylene and 7/10 (70%) for Dacron. Late patency for polypropylene grafts was better than for PTFE (p less than 0.05). Platelet aggregation status did not predict graft patency. Light microscopy of 2-week polypropylene explants showed inner capsules composed of myofibroblasts and macrophages, with patchy areas of endothelial cells lining the lumen. By 1 month, a confluent endothelialized surface was seen in all polypropylene explants. Progressive thickening of inner capsules with myofibroblasts and collagen continued through 4 months, reaching a mean thickness of 142 +/- 50 microns (compared to 150 +/- 30 microns for Dacron). These findings suggest potential clinical efficacy for polypropylene as an arterial substitute. PMID- 1429753 TI - Polyurethanes bearing pendant amino acids: fibrinogen adsorption and coagulant properties. AB - Segmented polyurethanes based on 4,4'-diphenylmethane diisocyanate and polypropylene oxide and chain extended with a sulfonated diamine were derivatized by reaction of sulfonate groups in the polymer with amino acids. The chemical composition of the derivatized polymers was determined by elemental analysis. Tensile stress-strain measurements indicated a slight increase in modulus and elongation with incorporation of amino acids. Water uptake at room temperature showed little change following derivatization, but at 70 degrees C increased significantly. Water contact angles were not influenced by the presence of amino acids, but electron spectroscopy for chemical analysis data showed an increase in hard segment content in the near-surface layers so that bulk and surface compositions were more nearly the same in the amino-acid-containing materials. Fibrinogen adsorption from plasma, shown previously to be high on the sulfonated polyurethanes, was reduced by derivatization, due probably to the decrease in free sulfonate content. Thrombin times of plasma in contact with these materials were essentially the same for the derivatized and underivatized materials. PMID- 1429754 TI - Theoretical analysis on cell size distribution and kinetics of foreign-body giant cell formation in vivo on polyurethane elastomers. AB - The nature of in vivo leukocyte adhesion and foreign-body giant cell (FBGC) formation on polyurethanes was studied through theoretical and statistical analyses in terms of cell size distribution, density changes, and kinetics of FBGC formation. The results showed that the size distribution of FBGCs followed a "most probable" distribution. During FBGC formation, the densities of FBGCs changed with time. At an early stage, the number of FBGCs increased with time to a maximum at the expense of macrophages. As more FBGCs were formed and less macrophages were present, the fusion of FBGCs among themselves became significant. This, in turn, caused a gradual decrease of FBGC density with time. The rate of FBGC formation was characterized by a rate constant that represented certain characteristics of cell fusion and FBGC formation and the density of initial FBGC-forming macrophages that were a small fraction of leukocytes adhering to the surface. The direct correlations of surface cracking and pitting and adherent FBGCs demonstrated the influence of phagocytic actions of FBGCs on the biostability of implanted polyurethanes. While the cracking was thought to be caused by oxidative degradation facilitated by oxygen ion/radical release of FBGCs, the pitting appeared to result from the Methacrol 2138F aggregates diffusing out of the polymer in an acidic microenvironment under FBGCs, which in turn could be enhanced by the surface degradation and cell phagocytosis. The added Santowhite powder in polyurethane had a significant influence on FBGC formation: It reduced FBGC density and rate of FBGC formation by reducing leukocyte adhesion and the number of macrophages participating in FBGC formation. PMID- 1429755 TI - Synthesis of antibiotic-loaded hydroxyapatite beads and in vitro drug release testing. AB - Various forms of hydroxyapatite (HAP) materials have been developed for use as bone grafts. Since the risk of local infection is associated with surgery, it seems reasonable to incorporate drugs such as antibiotics into implant materials. We therefore investigated the characteristics of drug incorporation into a spherical porous HAP bead (diameter = 8.48 mm, bulk porosity = 0.439) and its in vitro release behavior. Cefotiam (CTM) was used as a model antibiotic. Because of nonuniform pore distribution in the bead, distribution of CTM was estimated from the amounts of CTM experimentally determined at three different sites: the surface, halfway to the center, and the center of the beads. The results indicated that 90% of the drug was incorporated in the concentric outer 0.387 (radius = 1) section of the bead. CTM was released with a short lag time when the dry HAP bead was placed in water. Incorporation of CTM with egg phosphatidylcholine eliminated initial lag time and decreased the release rate of the drug from the bead. The lipid load was useful in controlling the release of CTM from the beads. In addition, to protect relatively unstable drugs from humidity and avoid contamination of drug-incorporated HAP beads an apparatus was designed with which the beads could be enclosed in vials in vacuo and under aseptic conditions on a bench-scale basis. PMID- 1429756 TI - Synthesis and nonthrombogenicity of polymer membrane with surface-graft polymers carrying thrombin inhibitor. AB - An acrylamide derivative of a thrombin inhibitor was synthesized and graft polymerized to the surfaces of polymer membranes. The thrombin-inhibitor activity was unaffected by the introduction of an acryloyl group. The surface-graft membrane deactivated thrombin markedly and suppressed adhesion of platelets, resulting in a high nonthrombogenicity. Immersion of polymer membranes blended with the thrombin inhibitor in phosphate-buffered saline for 10 d resulted in the loss of nonthrombogenicity, while the polymer membranes grafted with the thrombin inhibitor derivative maintained the nonthrombogenicity over a long period. PMID- 1429757 TI - Influence of calcium concentration on the dentin wettability by an adhesive. AB - Plane dentin surfaces were abraded perpendicular to the radicular axis of sound human molars. They were cleaned to reveal the tubules, and the morphological features of each surface were studied microscopically. For a first series of teeth, the Vickers microhardness of the dentin surfaces was measured and the calcium and phosphorus composition was determined by electron microprobe analysis. For a second series, the microhardness and wettability of the surface by the Scotchbond adhesive were compared. Positive correlations were found between the following parameters: degree of minerality, dentin compactness, hardness, and spreading capability of the adhesive. PMID- 1429758 TI - Relations between in vitro cytotoxicity and crosslinked dermal sheep collagens. AB - Collagen-based biomaterials have found various applications in the biomedical field. However, collagen-based biomaterials may induce cytotoxic effects. This study evaluated possible cytotoxic effects of (crosslinked) dermal sheep collagen (DSC) using a 7-d-methylcellulose cell culture with human skin fibroblasts. Non crosslinked DSC (NDSC), hexamethylene-diisocyanate-crosslinked DSC (HDSC), and glutaraldehyde-crosslinked DSC (GDSC), their extracts (1 x 10 d to 4 x 10 d extracts), or the corresponding extracted DSC samples were tested. Cell growth was evaluated by cell counting, while cell morphology was assessed by light microscopy and transmission-electron microscopy. Both GDSC and, to a lesser extent, HDSC, induced cytotoxicity, observed as inhibited cell growth and deviant cell morphology. The deviant morphology consisted of extensive accumulations of lipid, reduction in the amount and dilatation of rough endoplasmatic reticulum, increased inclusions of cell remnants, and relatively rounded cell membranes. With HDSC, both primary cytotoxicity, due to extractable products from the material, and secondary cytotoxicity, possibly due to a release of cytotoxic products resulting from enzymatic cell-biomaterial interactions, could be discriminated. With GDSC, however, no clear distinction between primary and secondary cytotoxicity could be made. With NDSC, only primary cytotoxicity, measured as low inhibition of cell proliferation, but without deviant morphology, was observed. These remarkable differences in cytotoxicity are discussed in relation to residual agents and specific crosslinks present in DSCs as a consequence of processing and the crosslinking agents used. The residual agents and the specific crosslinks give rise to differences in direct release of products and in sensitivity to hydrolysis and enzymatic breakdown. PMID- 1429759 TI - Short-term response of brain tissue to cerebrospinal fluid shunts in vivo and in vitro. AB - The purpose of the studies was to determine how gross physical characteristics of cerebrospinal fluid (CSF) shunts and the cellular proliferative response to shunts contribute to shunt obstruction. Ventricular catheters with round holes, slots, and flanges were implanted into the lateral ventricles of rabbits for 4 weeks. All shunt designs were subject to ingrowth of tissue from the ventricle wall or choroid plexus. There were no qualitative or quantitative differences between normal and hydrocephalic rabbits. Astroglial cells from newborn mice were cultured on shunt catheters for 2 or 4 weeks. The growth of these cells was poor, probably because the cells cannot attach well to the silicone rubber substrate. Contact between the shunt catheter and vascularized brain tissue is the most important factor in the genesis of shunt obstruction. PMID- 1429760 TI - Hydroxylapatite coating of porous implants improves bone ingrowth and interface attachment strength. AB - The effect of a plasma-sprayed hydroxylapatite (HA) coating on the degree of bone ingrowth and interface shear attachment strength was investigated using a canine femoral transcortical implant model. Cylindrical implants were fabricated by sintering spherical Co-Cr-Mo particles 500-710 microns in diameter; the nominal implant dimensions were 5.95 +/- 0.05 mm diameter by 18 mm in length. One half of each implant was coated with hydroxylapatite, 25-30 microns in thickness, by a plasma-spray technique. Using strict aseptic technique, the implants were placed through both femoral cortices into defects approximately 0.05 mm undersized. After 2, 4, 6, 8, 12, 18, 26, and 52 weeks, the implants were harvested and subjected to mechanical pullout testing and undecalcified histologic evaluation. The application of the HA coating to porous implants enhanced both the amount of bone ingrowth and the interface attachment strength at all time periods. These differences were statistically significant for the percent of bone ingrowth at the 4-, 6-, 12-, 18-, 26-, and 52-week time periods, and interface shear strength values were significantly different at the 6-, 8-, 12-, 18-, and 26-week time periods. The rate of development of interface strength and bone ingrowth was also more rapid for the HA-coated implants. No evidence of any disruption, mechanical failure, or biologic resorption of the HA coating was observed. The results of the present study--demonstrating a beneficial effect of the HA coating at all time periods--are believed to be due to the use of paired comparisons, which allow assessment of subtle differences that might otherwise have been obscured by normal biological variability. PMID- 1429761 TI - Microhardness measurements of renal calculi: regional differences and effects of microstructure. AB - Microhardnesses of five types of renal calculi: calcium apatite (82.5%)/magnesium ammonium phosphate hydrogen (10%)/calcium oxalate monohydrate (7.5%); calcium apatite (95%)/calcium oxalate monohydrate (5%); magnesium ammonium phosphate hydrogen (90%)/calcium apatite (10%); calcium oxalate monohydrate (85%)/calcium apatite (15%); and cystine (100%) were measured. Using Knoop and Vickers indenters the effects of chemical composition and microstructure on the microhardness measurement were assessed. Calcium oxalate monohydrate, magnesium ammonium phosphate hydrogen, and cystine stones, without apparent structure pattern, showed neither regional nor directional differences in their microhardness. In contrast, calcium apatite stones, with distinctly concentric laminae structure, showed regional variations which were correlated with the chemical composition of stone constituents. Scanning electron microscopy of the indenter impressions were taken to help in interpreting the directional dependence in Knoop hardness measurements with respect to the microstructure of the calculi. Vickers measurements showed the crystalline stones were isotropic within a layer. Combined results of Knoop and Vickers measurements indicate that the anisotropic Knoop hardness readings seen in the laminated regions were structural but not material-based. Implications of the results for the fragmentation of renal calculi in extracorporeal shock wave lithotripsy are discussed. PMID- 1429762 TI - In vitro corrosion fatigue of 316L cold worked stainless steel. AB - The corrosion resistance of 316L cold worked stainless steel depends upon its thin protective oxide layer; and if this is partially broken down, corrosion resistance depends upon its tendency for repassivation. Since the intended function of stainless-steel implants is to sustain musculoskeletal forces, research toward the stability of the oxide film during dynamic loading in simulated bodylike fluids is warranted. A pilot corrosion fatigue study was, therefore, performed on uniaxial tension fatigue specimens cycled to various maximum stress levels near their yield point while immersed in 37 degrees C isotonic saline solution, and combined with the electrochemical insult of (a) imparting an 800 mV vs. SCE anodic potential for 20 s to stimulate local film breakdown, and then (b) returning to a constant 200 mV vs. SCE anodic potential and maintaining that potential during cyclic loading until the specimens broke in two. During the anodic polarization by continuously monitoring the current it was possible to (a) observe the repassivation and corrosion behavior following stimulation, and (b) detect crack initiation, crack propagation and failure onset. The combined effects of accelerated corrosion and mechanical fatiguing disturbed the repassivation tendency and reduced the crack initiation times and the fatigue lives as compared to air and saline controls. As the maximum cyclic load levels were increased, the fatigue lives were further foreshortened. PMID- 1429763 TI - Tensile testing of tubular vascular grafts produced by thermal compression fusion of flat collagenous materials. AB - A novel process of fusion bonding for the production of vascular grafts has been investigated. This process, based on the application of pressure and heat in a sophisticated way, has been used for the bonding of the longitudinal edges of flat dermal sheep collagen into tubular forms. The method produces continuous overlapping joints which are expected to overcome the problem of coagulation, as occurs in grafts produced by suturing. The values of the measured shear strength of the bond vary from 750 +/- 30 kPa to 940 +/- 32 kPa, depending on tube diameter and overlap length (n = 5). These values are much higher than calculated values of the stress in thin-walled tubes caused by a high static blood pressure, indicating a high safety factor for the fusion-bonded vascular grafts. PMID- 1429764 TI - PEO enhancement of platelet deposition, fibrinogen deposition, and complement C3 activation. AB - Whereas it has been commonly thought that adding polyethylene oxide PEO to a surface would diminish the capacity of the surface to cause deposition of platelets and of fibrinogen, and to activate complement C3, we present data showing exactly the opposite. These unexpected results are obtained with low molecular weight (2000) PEO, and are not found with higher molecular weight (20,000) PEO. PMID- 1429765 TI - Calcification of implanted vascular tissues associated with elastin in an experimental animal model. AB - We have previously studied the process of calcification in bioprosthetic porcine heart valves crosslinked with glutaraldehyde. Observations using light microscopy had indicated that calcification of elastic fibers occurs in implanted heart valves, in addition to calcification associated with collagen fibers. To determine the contribution of elastin to the process of calcification, small pieces of rabbit aorta were cross-linked with 0.2% glutaraldehyde, rinsed in buffer, and implanted subcutaneously in young adult male rats. Cross-linked jugular vein implants were included as controls. After an implantation period of 1 month or longer, we observed many areas of calcification in the aortic media associated with elastin and fewer such areas associated with collagen. The elastin-rich aortic tissues accumulated more calcium than venous tissues. Calcium deposits appeared similar in both allogenic and xenogeneic implants. Calcified areas viewed under the electron microscope included intercellular nonfibrous material. Calcified areas involved predominantly the outer layers of elastic fibers. Calcific deposits included needle-like crystals of hydroxyapatite but often consisted of an amorphous flocculant material surrounded by crystals. The close spatial relationship of hydroxyapatite crystals and elastic membranes seen in this study may be relevant to the initiation of dystrophic calcification in glutaraldehyde cross-linked aortic grafts. PMID- 1429766 TI - Introducing a selectively biodegradable filament wound arterial prosthesis: a short-term implantation study. AB - This article introduces a new compliant and selectively biodegradable filament wound vascular graft and reports the findings of a short-term implantation study. A basic feature of filament winding is its ability to tailor and better control the mechanical properties of the prosthesis, so that a closer match with the anisotropic properties of native arteries is achieved. The elastomeric vascular grafts comprise poly(ether urethane urea) fibers (Lycra) embedded in a two component matrix consisting of poly(ether urethane) (Pellethane) and a highly flexible poly(ethylene glycol)/poly(lactic acid) biodegradable segmented copolymer (PELA). Typical tensile modulus values fall in the few megapascals (MPa) range, this being comparable to that of natural arteries. The wound graft exhibits excellent handling and suturability characteristics as well as enhanced burst strength. Furthermore, due to its biodegradable constituent, the prosthesis combines minimal intraoperative blood loss and high healing porosity. The graft displays initially negligible in vitro water permeation, which increases gradually with time. In this short-term study, the prostheses were implanted in the canine carotid, and their biological performance was compared to that of expanded Gore-Tex. The luminal surface of the wound grafts was coated with a thin layer of pseudointima, strongly adhered to the prosthesis surface. Contrasting with the very stiff Gore-Tex grafts, the filament wound prostheses retained their high compliance, being highly pulsatile upon explanation. Histological studies fully corroborated these findings, underscoring the healing properties of these new filament wound vascular prostheses. PMID- 1429767 TI - Antisera binding onto metals immersed in human plasma in vitro. AB - Titanium (Ti), silicon (Si), silver (Ag), vanadium (V), gold (Au), and chromium (Cr) surfaces were made hydrophilic by radiofrequency plasma treatment. The binding of antifibrinogen (a-fib) and anti-high-molecular-weight kininogen (a HMWK) after incubation of surfaces in 10% human blood plasma was investigated with ellipsometry. Ti and Si surfaces bound a-HMWK but no detectable amounts of a fib, whereas the other metals bound both types of antisera. Protein adsorption in a fluid gradient produced under a convex lens indicated that the small deposition of a-fib on Ti and Si surfaces is probably a result of protein displacement. This displacement was not evident at lens positions simulating low plasma concentrations where large amounts of a-fib adsorbed. Surfaces washed sequentially in trichloroethane, acetone, and ethanol produced more hydrophobic surfaces and resulted in slower rates of a-fib displacement. These studies would indicate that some metals form complexes with specific plasma proteins or, alternatively, that different metals may bind equal amounts of plasma proteins which express differing antigenicities toward their surroundings. PMID- 1429768 TI - Human neutrophil response to short-term exposure to F-75 cobalt-based alloy. AB - The effect of biomaterials on the activation of human neutrophils was studied. Human neutrophils were incubated with F-75 cobalt-based alloy or polystyrene microspheres of a nonphagocytosable size with two times total neutrophil plane surface area. Scanning and transmission electron microscope (SEM, TEM), energy dispersive x-ray microanalysis (EDX), and graphite furnace atomic absorption spectroscopy (GFAAS) were used to analyze changes in cellular morphology and metal content. This report presents evidence that human PMNs display morphological changes related to foreign material challenge, including activation on F-75 bead surfaces, pinocytosis of corrosion products, formation of intracellular vacuoles, degranulation, etc. Moreover, when PMNs were present, the corrosion release rate of F-75 increased as much as three times over cell-free controls. PMID- 1429769 TI - Prevention of tissue calcification on bioprosthetic heart valve by using epoxy compounds: a study of calcification tests in vitro and in vivo. AB - Calcification is the principal cause of the clinical failures of the bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. In this paper, we compared the calcification on various types of bovine pericardiums pretreated with two hydrophilic epoxy compounds adding GA post-treatment (EP 1 and EP 2), glutaraldehyde (GA)- and nontreated pericardium (Fresh), respectively, by in vitro and in vivo tests. Significant decrease of calcification was found by pretreatment with both epoxy compounds rather than with glutaraldehyde: 0.250 +/- 0.001 (Fresh), 0.276 +/- 0.058 (EP 1), 0.302 +/- 0.071 (EP 2), and 0.478 +/- 0.172 (GA) micrograms (Ca)/mg (dried tissue), respectively, after 20 days dipping in a simulating serum solution in vitro; 115.13 +/- 60.11 (Fresh), 129.84 +/- 51.08 (EP 1), 167.39 +/- 20.81 (EP 2), and 205.19 +/- 16.86 (GA) micrograms/mg, respectively, after 3 months subcutaneous implantation in rabbits. The in vitro method for evaluating calcification designed by us gave the similar order among four samples with that obtained by in vivo test. Because the bovine pericardium pretreated with the epoxy compounds adding GA post-treatment possesses the greater tenacity than that pretreated only with epoxy compounds or GA, meanwhile the calcification is also significantly decreased with this pretreatment, it may be expected that the bovine pericardium with this pretreatment will have the greater anticalcification and durability in dynamic stress. PMID- 1429770 TI - Polymeric hydrogels for soft contact lenses. PMID- 1429771 TI - Effect of child survival on contraceptive use in Bangladesh. AB - A study in Bangladesh showed that couples who lost a child often stopped practising contraception in order to have another child. Logistic regression analysis revealed that contraceptive continuation was related to maternal age, parity, husband's education and the sex of the last child. PMID- 1429772 TI - Estimating infant mortality rates prospectively in Honduras. AB - In order to determine the validity of infant mortality estimates based on retrospective reporting, the Honduran Ministry of Health carried out a follow-up survey of women interviewed in a 1987 national survey. Women were interviewed approximately 14 months after the baseline survey and were asked about the outcomes of their pregnancies and the survival status of their young children. The overall infant mortality rate calculated from the follow-up survey was lower than that obtained from the baseline survey, due to the particularly low rate among the group of women who were pregnant at the time of the baseline survey. Possible explanations for this low rate are discussed. PMID- 1429773 TI - A hazard logit model analysis of covariates of childhood mortality in Matlab, Bangladesh. AB - In a prospective study in Matlab, a rural area in Bangladesh, the relationship between a variety of covariates and childhood mortality was examined. Economic status of household, education of mother, sex of the children, health intervention programmes, age of mother, and live birth order of the children were identified as having a statistically significant impact on child survival when the effect of age was controlled. The effects of sex of the children, health programmes, age of mother, and birth order were found to be dependent on the age of the children, but the effect of mother's education was dependent on sex of the children. PMID- 1429774 TI - Determinants of current contraceptive use among Ghanaian women at the highest risk of pregnancy. AB - This study uses data from the Ghana Demographic and Health Survey (GDHS) of 1988 to examine factors determining the continued low levels of contraceptive use in Ghana. The women currently using efficient contraception are those who have sexual intercourse regularly, who discuss family planning with their partner, whose husbands approve of the use of family planning, and who live in the northern sector of the country. The finding that husband's approval is an important determinant of efficient contraceptive use has significant policy implications for Ghana and other African countries, to motivate both husbands and wives to share fertility control responsibilities. PMID- 1429775 TI - Some determinants of population variation in cortisol levels in a British urban community. AB - Urinary cortisol excretion rates were determined from three urine samples given over 2 days, a rest day and a working day, by 51 men and 50 women. Each subject also completed a questionnaire relating to life style factors and to perceived levels of stress, busyness and happiness on each day. In men, an association between raised cortisol and high levels of stress was found. In women, high levels of busyness were associated with low cortisol excretion rates. The subjective experiences measured accounted for around 10-20% of cortisol variation in this naturalistic setting. PMID- 1429776 TI - Secular trends of twinning rate in Sweden. AB - The change in parity and maternal age in Sweden accounts for the decline in the twinning rate from the 19th century to the middle of the 20th century. The later decline in twinning rate cannot be explained by changes in maternal age and parity. Fecundity appears to be higher in mothers of twins than in other mothers. PMID- 1429777 TI - Socioeconomic factors affecting the longevity of the Japanese population: a study for 1980 and 1985. AB - The effects of urbanisation, low income and rejuvenation of the population on life expectancy at birth and at 20, 40 and 65 years of age for males and females in Japan were examined twice, in 1980 and 1985. For males, urbanisation was the major factor determining life expectancy at birth and at age 20 years, and low income was the key determinant of decreased life expectancy except at 65 years of age. For females high income was the factor significantly decreasing life expectancy at 65 years of age in 1980, and rejuvenation of the population inversely influenced life expectancy except at birth in 1985. Life expectancy for all age groups in 1985 was significantly longer than in 1980 for both males and females. PMID- 1429778 TI - Geographical distribution of some Danish surnames: reflections of social and natural selection. AB - Geographical differences in the frequencies of eight common surnames in Jutland (Denmark) are analysed using data from telephone directories of 121 exchanges. All the names showed a significant geographical surplus variance, which was divided into trend and patchiness components reflecting the history of the names. The surplus variance of surnames with restricted areas of origin was dominated by a large trend component; for surnames with an originally more even distribution, the patchiness component was dominant. The patterns of distribution were affected by processes which modelled natural selection with linkage disequilibrium. The combined patchiness within the clusters of exchanges gave information about patterns of local migration and level of social integration in the communities. Areas situated in boundary regions show high levels of patchiness. PMID- 1429779 TI - Prevalence and determinants of caesarean section in Jamaica. AB - The prevalence and determinants of primary caesarean section in Jamaica were estimated from a survey of women aged 14-49 years. Among 2328 women reporting 2395 live hospital births during the period January 1984 to May 1989, the prevalence of caesarean section was 4.1%. Repeat caesarean sections accounted for 1.3% of the hospital births during that period. Of the medical complications studied, prolonged labour and/or cephalopelvic disproportion carried the highest risks of primary caesarean section, followed by breech presentation, maternal diabetes, a high birth-weight baby, maternal hypertension, and a low birth-weight baby. The risk of primary caesarean section increased with maternal age, decreased with parity, was higher for urban than for rural residents, and was higher for births in private versus government hospitals. PMID- 1429780 TI - Measurement of child mortality in association with a multipurpose birth certificate programme in the Southern Highlands Province of Papua New Guinea. AB - A simple and inexpensive method for monitoring child mortality in association with birth registration was introduced into the Southern Highlands of Papua New Guinea. Eight thousand two hundred and one newborn infants were registered in 1988, approximately 77% of all children born in that year. The risk of death by age 2 was determined from reports given by the mother on the present status of a previously born child at the time of a recent delivery or during clinic registration of the current birth. This was 91 per 1000 for the province and corresponds to a risk of death by age 1 of 77/1000 by extrapolation using standard lifetables. This method was validated by comparison with a continuing demographic surveillance system covering 30,000 people in the western part of the province. The new birth certificate has been an incentive to increase supervised delivery rates and to generate a register that can be used to increase vaccination coverage. PMID- 1429781 TI - Cognitive and educational attainment in different ethnic groups. AB - The educational attainment of over 2000 children aged 7-15 years from six different ethnic groups was assessed. Children of Pakistani and of Bangladeshi origin tended to obtain the lowest mean scores on all tests, often well below those of West Indian children, who tended to perform as well as Indian children and often no worse than the indigenous majority. There were few signs of any reliable trends over age. Differences were more pronounced on tests of reading and vocabulary than on tests of mathematics but, on tests of non-verbal reasoning, most ethnic minorities also obtained low scores. Many of these differences were associated with differences in social and family circumstances. PMID- 1429782 TI - Relations between fertility, body shape and menopause in Austrian women. AB - The influence of number and date of pregnancies, births, and spontaneous and induced abortions on body shape, age at menopause and menopausal symptoms have been studied for 110 postmenopausal Viennese women. A significant correlation between fertility and age at menopause was not found, but several menopausal symptoms showed statistically significant correlations with fertility. With a higher number of pregnancies the individual symptoms became more severe. PMID- 1429783 TI - Compression plating for non-union after failed external fixation of open tibial fractures. AB - Fifty non-unions of the tibia that were present in forty-nine patients after external fixation and immobilization in a cast for a high-energy fracture were subsequently treated by compression plating. Initially, there were forty-six open fractures and four closed fractures with a compartment syndrome. Twenty-two non unions (44 per cent) had early soft-tissue reconstruction (thirteen rotational and nine free flaps). The duration of external fixation averaged ten weeks, and the mean time from injury to plating was eight months. None of the non-unions were infected at the time of plating. The average preoperative deformity in the sagittal (anterior-posterior) plane was 8 degrees and in the frontal (medial lateral) plane, 9 degrees; after plate fixation, the residual angulation averaged 3 and 2 degrees. Autogenous bone graft was used in thirty-nine of the fifty non unions. The patients were followed for an average of twenty-four months. Forty six (92 per cent) of the non-unions united, in an average of seven months, without further intervention. In four patients (8 per cent), the plate broke, necessitating re-plating in three and external fixation in one (the latter patient had an infected non-union). A deep infection developed in three patients (6 per cent). Ultimately, forty-eight non-unions (96 per cent) healed without evidence of infection. Plate osteosynthesis is an effective method of treatment for patients who have had an open fracture of the tibia that has failed to unite after external fixation and immobilization in a cast. PMID- 1429784 TI - Indirect reduction and tension-band plating of tibial non-union with deformity. AB - Thirty-three patients who had a maligned non-union of the tibial diaphysis were treated by limited open exposure, indirect reduction with a femoral distractor, tension-band plating, lag-screw fixation, and autogenous bone-grafting. The time from the injury to treatment of the non-union averaged twenty-nine months. Twenty two of the fractures were originally open and sixteen fractures had had a previous infection before treatment of the non-union. The non-unions were classified as hypertrophic in eight patients, oligotrophic in eighteen, and atrophic in seven. All had severe deformity, or the nature or level of the non union, or both, precluded intramedullary nailing as a treatment option. All thirty-three non-unions healed at an average of four months; the average length of follow-up was nineteen months. The deformity was corrected, within acceptable limits, in thirty-two of the patients. Full motion of the knee was achieved in twenty-nine patients and of the ankle, in eighteen. Complications included four instances of superficial skin breakdowns, one deep infection, and one fracture of the plate. For non-unions of the tibial diaphysis with deformity that are not amenable to intramedullary nailing, the techniques of limited exposure, indirect reduction, tension-band plating, and bone-grafting can yield excellent anatomical and functional results. PMID- 1429785 TI - The effect of functional knee-braces on strain on the anterior cruciate ligament in vivo. AB - Functional knee-braces are widely used to protect injured or reconstructed anterior cruciate ligaments, despite the fact that few scientific data support their efficacy. We studied seven functional braces, representative of both the typical custom-fit and off-the-shelf designs. The braces were tested on subjects who had a normal anterior cruciate ligament and were scheduled for arthroscopic meniscectomy or exploration of the knee under local anesthesia. After the operative procedure, a Hall-effect strain-transducer was applied to the anterior cruciate ligament. Under low anterior shear loads, two braces provided some protective strain-shielding effect compared with no brace, but this strain shielding effect did not occur at the higher anterior shear loads expected during the high-stress activities common to athletic events. The DonJoy, Townsend, C.Ti., and Lenox Hill braces demonstrated a strain-shielding effect on the anterior cruciate ligament with an internal torque of five newton-meters applied to the tibia. None of the braces had any effect on strain on the anterior cruciate ligament during active range of motion of the knee from 10 to 120 degrees or during isometric contraction of the quadriceps. Wearing of a brace did not produce an increase in the value for strain on the anterior cruciate ligament. For the activities that were evaluated in this study, none of the braces produced adverse effects on the anterior cruciate ligament, and there were no significant differences in the strain on the anterior cruciate ligament between the use of a custom-fit or an off-the-shelf brace design. There were no apparent advantages of the more expensive custom-made braces compared with the off-the-shelf designs. PMID- 1429786 TI - Comparison of reconstruction of the anterior cruciate ligament with and without a Kennedy ligament-augmentation device. A randomized, prospective study. AB - In a randomized, prospective study, sixty-four patients who were operated on for a torn anterior cruciate ligament were divided into two groups: thirty patients (the control group) had repair with the Marshall-MacIntosh technique alone, and thirty-four patients had repair with the same technique but with the addition of a Kennedy ligament-augmentation device. The preoperative characteristics were essentially identical in the two groups. The postoperative management, resumption of athletic activities, and occurrence of complications were also similar. All patients were followed for more than two years. No significant functional or clinical difference between the two groups was found with respect to residual laxity determined either from dynamic radiographs or with the KT-1000 arthrometer. There was no evidence that the addition of the Kennedy ligament augmentation device gave results that were superior to those obtained with the Marshall-MacIntosh technique alone. PMID- 1429787 TI - Isokinetic and isometric measurement of strength of external rotation and abduction of the shoulder. AB - The strength of active external rotation and of abduction of the shoulder when the humerus was in the plane of the scapula (30 degrees of horizontal flexion anterior to the coronal plane) was measured isokinetically and isometrically in thirty-nine normal volunteers, who were stratified by age and sex. The angles at which peak torque was produced were similar when tested isokinetically and isometrically; these angles were similar for external rotation (at 60 and 30 degrees of internal rotation) and for abduction (at 30 and 60 degrees of abduction). Isometric peak torque was greater than slow-speed (90 degrees per second) isokinetic peak torque, which in turn was greater than fast-speed (210 degrees per second) isokinetic peak torque. There were highly significant differences in strength, measured isokinetically and isometrically, between younger and older men and between older men and older women. The variability of normal values for torque was similar in each group. Repeat testing demonstrated a high reliability of isokinetic measurements and of isometric measurements at angles within the range of the production of peak torque. Complete testing was performed in four normal volunteers before and after a block of the suprascapular nerve. The supraspinatus and infraspinatus components of the rotator cuff contributed a variable proportion to the total strength of abduction (25 to 50 per cent) and external rotation (50 to 75 per cent) throughout the range of motion. This study demonstrated that both isokinetic and isometric testing in the scapular plane are valid methods for measurement of the strength of external rotation and abduction of the shoulder. The data support standardization of the positions for testing the strength of motions of the shoulder: isometric strength of external rotation should be measured in the scapular plane with the shoulder in 45 degrees of abduction and 45 degrees of internal rotation; isometric strength of abduction, in the scapular plane with the shoulder in 45 degrees of abduction; and isokinetic strength of external rotation and abduction, in the scapular plane at 90 degrees per second. PMID- 1429788 TI - Operative correction of an unstable total hip arthroplasty. AB - We reviewed the results of reoperation in ninety-five patients who had acute subluxation (ten patients) or dislocation (eighty-five patients) of the hip after conventional cemented total hip-replacement arthroplasty. Postoperatively, fifty eight patients (61 per cent) had no subsequent dislocation or subluxation. Seven of thirty-seven patients who had had recurrent dislocation had occasional subluxation during follow-up. Of the remaining thirty patients in whom instability persisted after the reoperation, twenty-eight had at least one dislocation, and nine had bothersome subluxation. Ten of these thirty-seven patients had another operation for the persistent instability. The causes of instability were classified as malrotation of the component, disruption of the trochanteric-abduction mechanism, impingement, or multiple and unknown, and appropriate treatment was provided. The component was revised in forty-five patients, revision and advancement of the trochanteric component was done in twenty-five patients, and impinging bone or cement was removed from six patients; a combination of these procedures was done in nineteen patients. Over-all, fifty eight procedures (61 per cent) were successful (no additional subluxations or dislocations). We concluded that the results of operative treatment for an unstable total hip replacement can be optimized when a precise determination of the cause of the instability is made and appropriate measures are applied. PMID- 1429789 TI - Prophylaxis with indomethacin for heterotopic ossification after Chiari osteotomy of the pelvis. AB - One hundred patients who had painful dysplasia of the hip were treated with a Chiari osteotomy of the pelvis, and the postoperative radiographs were reviewed for the development of heterotopic ossification. Sixty patients did not receive indomethacin postoperatively, and eighteen (30 per cent) had heterotopic ossification of at least class 1; forty patients received indomethacin for two weeks postoperatively, and only three (8 per cent) of them had heterotopic ossification. This difference was significant (p < 0.025). No class-3 or 4 heterotopic ossification was seen in the patients who were given indomethacin. The prevalence of side-effects was relatively low, and no delayed union of the osteotomy was observed in any patient. We concluded that indomethacin, in the dosage schedule and regimen that we used, provides effective prophylaxis for heterotopic ossification after a Chiari pelvic osteotomy. PMID- 1429790 TI - One-stage correction of the spastic dislocated hip. Use of pericapsular acetabuloplasty to improve coverage. AB - We performed a combined one-stage approach for the treatment of eighteen spastic subluxated or dislocated hips in eleven children who had cerebral palsy. All patients were between five and thirteen years old and had spastic subluxation or dislocation of the hip and severe acetabular dysplasia. The operation consisted of release of the adductors, psoas, and proximal hamstrings; a femoral-shortening varusderotation osteotomy; and a pericapsular pelvic osteotomy. The pelvic osteotomy was designed to increase superolateral coverage of the femoral head in the elongated acetabulum, which had erosion of the superior and lateral aspects. At the latest follow-up (mean duration, six years and ten months), seventeen of the eighteen hips remained anatomically reduced. PMID- 1429791 TI - Improved preservation of skeletal muscle in amputated limbs using pulsatile hypothermic perfusion with University of Wisconsin solution. A preliminary study. AB - To determine whether pulsatile hypothermic perfusion with University of Wisconsin preservation solution is superior to topical cooling as a method for the preservation of amputated limbs, six pairs of amputated canine limbs were preserved for twelve to fifteen hours. One limb of each pair was subjected to topical cooling and the other, to pulsatile hypothermic perfusion with University of Wisconsin solution. The bioenergetic status of the limbs was monitored by 31phosphorus magnetic-resonance spectroscopy, and histological evaluation was performed to assess ischemic changes in the preserved tissue. The pH and tissue levels of adenosine triphosphate declined three times more slowly in the limbs that were preserved by pulsatile hypothermic perfusion than in the topically cooled limbs. Consistent with these findings, the perfused limbs also had less histological evidence of ischemic injury. The data from this in vitro study show that pulsatile hypothermic perfusion with University of Wisconsin solution, in combination with an optimum degree of topical cooling, is superior to topical cooling alone as a method of preserving the bioenergetic status of amputated limbs. PMID- 1429792 TI - Juvenile hallux valgus. A conservative approach to treatment. AB - A conservative method consisting of use of a thermoplastic splint at night as well as passive and active exercises was used for the treatment of hallux valgus in fifty-six children and teen-agers who were between one month and sixteen years old. The splint was remodeled periodically. At the time of follow-up, which ranged from two to six years, the metatarsophalangeal joint angle or the intermetatarsal angle, or both, had improved in approximately half of the feet. No recurrences were detected among the patients who improved. PMID- 1429793 TI - Changes in growth-plate morphology associated with rejection of rat-limb allografts. AB - Histological and electron microscopic studies were performed to demonstrate the changes in the morphology of the growth plate that occur in allografts obtained from the limbs of growing rats. A genetically defined model was used in which the right hindlimbs of Lewis rats were orthotopically transplanted into Fischer-344 recipient rats. These strains are matched for major histocompatibility antigens but mismatched for minor histocompatibility antigens. The disparity at the minor histocompatibility complex between the Lewis donors and the Fischer recipients creates a weak histocompatibility barrier to transplantation. Lewis-to-Lewis syngeneic limb grafts were used as controls. The proximal parts of the transplanted tibiae were excised during acute rejection of the allograft on days 1, 5, 8, 11, 14, and 28 postoperatively. During rejection, a widened zone of calcified cartilage in the growth plate was observed at eleven days; this zone increased progressively thereafter. The number of chondroclasts in the primary spongiosa of the metaphysis had decreased significantly at eleven days, and chondroclasts had disappeared completely at fourteen days, in association with mononuclear cell infiltration. Electron microscopic examination revealed inactive morphology in some chondroclasts at eight days, and the number of inactive chondroclasts had increased significantly on day 11. At fourteen days, there were no viable chondroclasts in the primary spongiosa, and only remnants of degenerated chondroclasts were present. These findings suggest that the chondroclasts were early targets of rejection and their loss resulted in the cessation of resorption of the calcified cartilage. However, the proliferation and maturation of chondrocytes in the growth plate and the calcification of the matrix continued, despite progression of rejection in the metaphysis. Thus, survival of the chondrocytes and rejection of the chondroclasts apparently led to the formation of a widened calcifying zone in the growth plate. PMID- 1429794 TI - Distal lengthening of the hamstrings in patients who have cerebral palsy. Long term retrospective analysis. AB - One hundred and twenty-six patients who had cerebral palsy and who had been managed with distal lengthening of the hamstrings were followed for three to fourteen years so that the long-term results of the procedure could be determined. Twenty-four of sixty-two patients who could not walk before the procedure were able to walk about the house postoperatively. Mild recurvatum developed in only ten patients, and twenty-two patients had a reoperation because of recurrence. Although straight-leg raising and the popliteal angle had improved markedly at one year in all but two patients, both parameters regressed gradually over time. Of several selected variables, only limitation of straight-leg raising preoperatively was of statistical significance (p < 0.001) for the prediction of recurrence. Age, preoperative walking ability, concomitant operations, and postoperative immobilization had no significant effect on the rates of recurrence or recurvatum. PMID- 1429795 TI - The Ellison iliotibial-band transfer for a torn anterior cruciate ligament of the knee. Long-term follow-up. AB - We studied the long-term results of the Ellison technique of extra-articular transfer of the iliotibial band, without advancement of the biceps tendon, as the sole operative treatment for a torn anterior cruciate ligament. Thirty-two patients (thirty-two knees) were evaluated an average of eleven years (range, seven to fifteen years) after the operation. The average age at the time of the operation was twenty-two years (range, sixteen to thirty-four years). Eighteen patients (56 per cent) had a modified Lysholm score of less than 84 points, indicating symptoms during the activities of daily living. Only six patients (19 per cent) had a subjectively normal knee (a modified Lysholm score of more than 94 points). The most common reason for a poor subjective score was the presence of symptoms of instability, in twenty-four patients (75 per cent). Twenty-four patients (75 per cent) had a positive pivot-shift test and twenty-nine patients (91 per cent), a positive Lachman test. Twelve patients (38 per cent) had severe (grade 3 or 4) radiographic changes. The radiographs of the knee appeared normal (grade 0) in only eight patients (25 per cent). There was a significant association between a meniscal injury and radiographic changes (p < 0.05). Fourteen patients (44 per cent) had subsequent procedures due to persistent instability or pathological changes in the articular cartilage or in a meniscus. There was a significant decline in the subjective and objective knee scores in the twenty-one patients who were evaluated at both two and eleven years. The number of patients who had a positive pivot-shift test increased from five (24 per cent) to sixteen (76 per cent). Subjectively, the number of patients who had a good result decreased from fourteen (67 per cent) to five (24 per cent). Objectively, nine patients (43 per cent) had a rating of good at two years; this fell to three (14 per cent) at eleven years. Symptomatic instability, pain, and a positive pivot-shift test were the most common reasons for a poor result. Because of the decline in the subjective and objective scores, we no longer recommend the Ellison procedure as the sole operative treatment for a torn anterior cruciate ligament of the knee. PMID- 1429796 TI - Compression of the left main-stem bronchus in a patient who had Duchenne muscular dystrophy. A case report. PMID- 1429797 TI - Identification of non-metallic foreign bodies in soft tissue: Eikenella corrodens metatarsal osteomyelitis due to a retained toothpick. A case report. PMID- 1429798 TI - Neuropathic arthropathy associated with neurofibromatosis. A case report. PMID- 1429799 TI - Charcot joint disease of the shoulders in a patient who had familial sensory neuropathy with anhidrosis. A case report. PMID- 1429801 TI - Non-union of fractures of the mid-shaft of the clavicle. Treatment with a modified Hagie intramedullary pin and autogenous bone-grafting. PMID- 1429800 TI - A normal data base of posteroanterior roentgenographic measurements of the wrist. AB - In 120 adults, we measured the dominant wrist on posteroanterior roentgenograms in order to determine the normal dimensions and variations according to age and sex. Men and women were equally represented as were two age-groups (twenty-five to forty years and forty-one to sixty years). The roentgenograms were made, with standard exposure and development techniques, with the wrist and forearm in a neutral position and the x-ray tube aligned vertical to the radial styloid. The roentgenogram that was made with the wrist in the mid-coronal plane was digitized and was used to measure distances between specified landmarks. The mean ulnar variance was -0.9 millimeter (normal range, -4.2 to 2.3 millimeters). The average carpal height ratio was 53 per cent (normal range, 46 to 61 per cent). The mean radial inclination was 24 degrees (range, 19 to 29 degrees). The carpal-radial and carpal-ulnar ratios were smaller in women. The width of the distal radio ulnar joint was reduced in the older subjects. There was a significant positive relationship (p < 0.0001) between the maximum force reached and the length of the third metacarpal. We believe that information concerning the normal roentgenographic measurements and relationship between the bones of the wrist can be used (1) to follow the progression of carpal instabilities, osteonecrosis, osteoarthrosis, or rheumatoid arthritis; (2) in clinical research; and (3) in the design of wrist implants. PMID- 1429803 TI - Release and excretion of metal in patients who have a total hip-replacement component made of titanium-base alloy. PMID- 1429802 TI - Radial wedge osteotomy for Kienbock disease. PMID- 1429804 TI - 9th Combined Meeting of the Orthopaedic Associations of the English-Speaking World. Toronto, Canada, June 21-26, 1992. Abstracts. PMID- 1429805 TI - British Scoliosis Society. Belfast, United Kingdom, March 20, 1992. Abstracts. PMID- 1429806 TI - British Orthopaedic Research Society, meeting. Nottingham, United Kingdom, April 2-3, 1992. Abstracts. PMID- 1429807 TI - Growth hormone and cortisol secretion in patients with burn injury. AB - A prospective study of growth hormone, insulin-like growth factor (IGF-1), and cortisol secretion was undertaken in six adults with burn injury. Serum concentrations of growth hormone and IGF-1 were low in all patients during the first 2 weeks of hospitalization. The mean growth hormone level was 4.35 +/- 0.83 micrograms/L on day 1 and 1.70 +/- 0.50 micrograms/L on day 13. The mean serum concentration of IGF-1, which reflects overall growth hormone secretion, was 0.43 +/- 0.09 U/ml on day 1 and 0.61 +/- 0.11 U/ml on day 13; these values are distinctly low. After 3 to 4 weeks, IGF-1 concentrations increased to the mid normal range, whereas growth hormone values did not change. Morning plasma cortisol concentrations were modestly elevated; however, urine free cortisol concentrations, which reflect total cortisol secretion, were elevated 2 to 28 times above normal values at the time of admission (mean, 443.5 +/- 323.7 nmol/L). Urinary free cortisol concentrations remained elevated after 2 weeks (mean, 230.5 +/- 94.5 nmol/L). Patients with burn injury have inappropriately low growth hormone secretion and IGF-1 production in spite of the stress of the injury and more than adequate nutritional therapy. PMID- 1429808 TI - The effects of epinephrine, ibuprofen, and tetrachlorodecaoxide on cutaneous microcirculation in thermally injured hamsters. AB - Fluctuations in the diameter of selected arterioles in the cutaneous microcirculation of Syrian golden hamster dorsal skin flap chambers, which ranged in size from 10 to 70 microns at different branching order sites, were measured before burn, at the same sites after burn and after injection of the drug. Three different drugs epinephrine (administered intravenously), ibuprofen (administered intravenously), and tetrachlorodecaoxide (administered intravenously and topically) were evaluated. Results show that the response to thermal injury in the control group involved extensive vasodilation in the arterioles, prolonged flow irregularities including flow obstructions and stasis, and a decrease in the level of vasoactivity of the microvessels. In two treatment groups, the ibuprofen and tetrachlorodecaoxide groups, significant improvement as indicated by reduced vasodilation and edema and improved microcirculatory blood flow after injury were observed. Further testing of tetrachlorodecaoxide as a topically applied wound dressing is indicated. PMID- 1429809 TI - Reversible burn injury. AB - Treatment of the patient with burns has advanced dramatically during the last several decades. Patients with burns that cover a greater percentage of the body surface area are now surviving. Cardiac, pulmonary, and vascular insults are better understood and more adequately treated. Nutritional requirements of the patient with burns can be fulfilled, and physical therapy is providing improved quality of life. In spite of these advances, care of burned tissue has progressed only moderately. The introduction of silver nitrate and other topical antibiotics and early excision significantly improved burn care. Other advances are not in widespread use in spite of research data that detail beneficial alternatives or additions to current therapies. Specifically, reversal of burn injury is possible. The research in this field had progressed considerably to the present. Reversal of dermal vascular occlusion in burned tissue seems to preserve that tissue. PMID- 1429811 TI - Management of cutaneous manifestations of extensive purpura fulminans in a burn unit. AB - Purpura fulminans is a rare disease, which may have devastating cutaneous manifestations. It usually follows an infectious illness, and although it most commonly occurs in children, it can occur in adults. The pathogenesis may be related to a relative deficiency of protein C and/or protein S. A case of an adult male is presented to illustrate the management of the severe full-thickness skin loss and the use of surgical excision and allograft in this disease. PMID- 1429810 TI - Antibiotic iontophoresis in the management of burned ears. AB - Severe deformities of the ears are a distressing problem after burn injury. Successful management of chondritis has been elusive. Antibiotic iontophoresis has been used in the management of burned ears in patients who have been admitted to the St. Vincent Medical Center Burn Unit since 1983. There were 145 ear burns in 92 consecutive patients who received prophylactic penicillin or gentamicin iontophoresis and who were admitted from 1983 through 1990. A retrospective analysis of all patients who were admitted to the burn unit from 1967 to 1983 was done to review the outcome for patients with burned ears when conventional treatment was used. The incidence of infection, need for chondrectomy, and ear infection were virtually eliminated by management with antibiotic iontophoresis. In addition, no complications were noted when antibiotic iontophoresis was used. Antibiotic iontophoresis provides a safe, simple, and effective way to manage burned ears and thereby limits postburn ear deformities. PMID- 1429812 TI - Automobile carburetor- and radiator-related burns. AB - Seventy-nine persons who had sustained automobile engine carburetor- and radiator related burns were admitted to Grady Memorial Hospital Burn Unit between June 1, 1984 and September 30, 1990. Forty patients with carburetor-priming flame burns had a mean age of 31.5 years, a mean burn size of 13.4% total body surface area, and a mean length of stay of 13.8 days. There were 37 male patients. Four patients had an inhalation injury. Twenty-two surgical procedures were performed on 13 patients. One patient was an innocent bystander, and one patient died. The clothing of 16 patients had ignited, which resulted in larger, deeper burns and in one death. Burns predominantly involved the right sides of the face, head, and torso; the right upper extremity; and the right hand. Thirty-nine patients had scald burns that were associated with uncapping a radiator. These patients had a mean age of 29.6 years, a mean burn size of 8.9% total body surface area, and a mean length of stay of 6.4 days. There were 36 male patients and three innocent bystanders. One autografting procedure was performed, and there were no deaths in this group of patients. The burn-prone person is the young adult male. The circumstances that result in such dangerous behavior are predictable, and resultant burn injuries are preventable. PMID- 1429813 TI - Burns caused by automobile radiators: a continuing problem. AB - In spite of the fact that injury warning labels have been placed on radiator caps for the last 15 years, automobile radiator scald burns continue to be a burn prevention problem. The temperature of radiator fluid may be as high as 100 degrees F to 250 degrees F in a properly functioning car and higher in an overheated vehicle. From 1974 to 1990, 100 patients with burns that were caused by automobile radiators have been admitted to the Parkland Memorial Hospital Burn Unit (1.5% of acute admissions). Eighty-two percent of the injuries occurred in the summer months, and 93% of the patients were male. Mean age was 31 +/- 17 years (range, 8 months to 79 years), and mean burn size was 11.3% total body surface area (TBSA) (range, 1% to 32%) with a mean full-thickness burn size of 0.6% TBSA. Length of stay was 7 +/- 7.4 days (range, 1 to 38 days). Burns to the face, neck, and trunk necessitated most admissions. Although there were no deaths, five patients required intensive care for airway monitoring; mean length of stay was 6 days. One patient required endotracheal intubation for a total of 11 days. Ten patients required one or more skin grafting procedures, and three patients required burn resuscitation. Four patients sustained minor ocular injuries. A subgroup of patients demands special review: 10 children younger than 10 years of age (mean age, 4.1 years) of which 70% were boys. Mean burn size was 15.5% TBSA; mean full-thickness burn size was 2.4% (four times larger than the mean burn size for the adult population).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429814 TI - The burn unit experience at Grady Memorial Hospital: 844 cases. AB - Between February 20, 1987 and July 13, 1990, 844 patients were admitted to the Grady Memorial Hospital Burn Unit. Mean age was 25.5 years, mean burn size 16.5% total body surface area, mean survivor hospital length of stay 15.9 days, and an overall survival 90.5%. Seventy-three percent were male. One half of the burns were less than 10% total body surface area. Almost half (48.5%) of the patients had flame burns, which accounted for 88.8% of the 80 deaths. The peak burn incidence occurred in infants and children as a result of scalds. If those with toxic epidermal necrolysis (n = 5), those without skin injury (n = 13), and those who were allowed to die (n = 16) are excluded, survival was 92.2%. Survival in 62 patients with inhalation injury (55.23%) was significantly less than that in 474 patients without inhalation injury (98.10%) (p less than 0.0001). The three variables--age, burn size, and inhalation injury--each influenced survival significantly but appeared to be dependent on each other; all three tended to increase or decrease together. Logistic regression equations to predict survival were developed. PMID- 1429815 TI - The relationship of burn wound fluid to serum creatinine and creatinine clearance. AB - A case is presented with emphasis on creatinine clearance and burn wound closure. It suggests that the burn wound acts as an extrarenal site for creatinine loss. As a result, renal creatinine clearance may be falsely elevated while the burn wound is open, and closure of the burn wound may affect creatinine clearance. PMID- 1429816 TI - Major thermal burn as a result of intraoperative heating blanket use. AB - A 72-year-old woman sustained a 30% full-thickness total body surface area burn as a result of a malfunction in a heating blanket during coronary artery bypass surgery. Early burn wound excision and wound closure with skin grafts were performed. The patient experienced wide swings in systolic blood pressure. She was treated with antibiotics and received maximal mechanical support. However, cardiac collapse occurred, and the patient died on the tenth day after burn injury. Previous case reports have discussed only minor burns that resulted from heating blanket use. The magnitude of this injury and the death that resulted from it highlight the importance of preoperative and intraoperative equipment checks and careful intraoperative core temperature monitoring. PMID- 1429817 TI - Multiple brain abscesses complicating treatment of a severe burn injury: an unusual case report. AB - Death after burn injury is usually due to complications, of which bacterial causes are dominant. We treated a patient with a burn injury who had the unusual complication of multiple brain abscesses, which were caused by methicillin resistant Staphylococcus aureus (MRSA). The patient, a 27-year-old man, had MRSA septicemia on day 9 and pneumonia on day 18. Hemiparesis, which was the first manifestation of brain abscesses, occurred on day 27. Although antibiotics were administered aggressively, the infection was never resolved, and the patient died on day 50. Brain abscesses and MRSA infection are still major problems in the treatment of burns. This is the first report of (metastatic) multiple brain abscesses complicating treatment of a burn injury. PMID- 1429818 TI - Positioning screen. PMID- 1429819 TI - Personal emergency response systems. AB - A personal response system is a signaling device that summons help during an emergency. Although personal response systems vary widely, there are three components. The first component is the electronic hardware in the home, which consists of portable and installed sensors and the control console. The second component is the emergency response center, which is either provider-based or manufacturer-based. The third component involves the dispatch of appropriate assistance. The primary users of personal response systems are women in their seventies and eighties who live alone and who have cardiac and musculoskeletal problems, which make them prone to falls. The frequency of personal response system use varies from an average of 0.44 to 0.84 emergencies per subscriber per year. Program coordinators believe that personal response systems help to delay institutionalization, reduce admissions to hospitals, substantially shorten hospital stays, and reduce the duration of home attendant services. The most favorable impact of the personal response system has been its psychologic value to the users and their families. PMID- 1429820 TI - Splinting the pediatric Palmar burn. AB - Children younger than 4 years of age who have sustained deep palmar burns pose a significant challenge to the burn care team. Flexion contractures of the palm and digits are all too common because the hand is maintained in flexion when at rest and while engaged in functional activities. A splint that positions the wrist in extension and the metacarpophalangeal joints of digits 2 to 5 in some hyperextension was evaluated. Nine patients with acute burns and two patients who required palmar reconstruction were studied. (The total number of hands was 15.) With this splinting technique, we have successfully maintained the antideformity position in patients with acute injuries and in those who have undergone reconstructive procedures. PMID- 1429821 TI - The benefits of plaster casting for lower-extremity burns after grafting in children. AB - Plaster casts are frequently used for immobilization of extremities after grafting in our burn center. A retrospective study was undertaken to evaluate the efficacy of this technique versus posterior splinting in children with burns below the knee. Thirty-six of 165 patients who required skin grafts from October 1986 to October 1989 received skin grafts to the lower extremity below the knee. Twenty patients (56%) were casted and 16 (44%) were not. Various parameters were analyzed in order to compare the casted versus noncasted groups. Several statistical techniques were used to compare the two groups. The casted group had younger children, more rapid wound closure, fewer therapy treatments, and more complete graft take. When sheet and meshed grafts were compared, the same variables were significantly improved for only the group that received meshed grafts. The use of plaster casting after skin grafting is a cost-effective method of improving patient care. PMID- 1429822 TI - Continuous enteral feeding and short fasting periods enhance perioperative nutrition in patients with burns. AB - Both retrospective and prospective analyses of the effects of various fasting regimens were carried out on the achievement of calculated caloric needs of patients with severe burns. The records of patients who received enteral feedings while undergoing burn debridements were divided into three groups and retrospectively analyzed to determine the effect that duration of fasting had an achievement of caloric needs and on the risks of aspiration. Patients in two other groups were prospectively studied to determine the safety and efficacy of stopping continuous enteral feedings 1 and 4 hours before surgery, respectively. Techniques of airway management and anesthetic induction were left to the discretion of the attending anesthesiologist. In the retrospective analysis, patients in group I, who fasted for 2 hours achieved 28% of their calculated 24 hour caloric goals compared with 11% in those who fasted for 2 to 8 hours (group II) and 6% in those who fasted for more than 8 hours (group III) before surgery (p less than 0.001). In the prospective portion of the study, patients who fasted for 1 hour before anesthesia was induced achieved 30% of their caloric needs, whereas those who fasted for 4 hours achieved 15% of their target nutritional needs (p = 0.0001). No patient had evidence of pulmonary aspiration. We conclude that controlled enteral feedings and shortened preoperative fasting periods can safely enhance nutritional support in patients with burns. PMID- 1429823 TI - The effect of instruction on burn prevention in eighth-grade students in preparation for babysitting. AB - New parents quickly discover that the greatest resource for child care at the least cost are teenage babysitters. These sitters assume the responsibility for burn prevention of young children. This study tested the effect of a burn prevention presentation on pre- and posttest scores of eighth-grade students (N = 119) from five sections of a science class. Students were between the ages of 12 and 14 years and 99 of them (83.2%) were babysitters. Multiple analysis of variance was calculated, and differences were seen between information regarding burns from hot bath water, cigarette lighters, and baby bottles that were heated in microwave ovens; however, the differences were not significant. This study concluded that eighth-grade students learned burn prevention before they entered the eighth grade but that there is a need to update these babysitters on burn prevention and new hazards such as cigarette lighters and microwave ovens. PMID- 1429824 TI - The impact of burn injury: a preliminary investigation. AB - Thirty-eight individuals who had been previously hospitalized for burn injuries were interviewed about the problems that they had experienced as a result of their injuries, their rehabilitation goals, and factors that they believed had influenced either the rate or extent of their recovery. The problems that were most frequently mentioned by participants were compared with problem areas that are covered by the Burn-Specific Health scale, which is a standardized measure designed to assess the impact of burn injury. Our findings suggest that although many problem areas are well covered by the Burn-Specific Health scale, other areas are covered less well. Thus more work is needed to refine the scale to capture more fully the wide variety of problems that are experienced by survivors of burn injuries. In general, patients' rehabilitation goals reflected the types of problems they experienced. Support from health care providers was the most frequently mentioned facilitator to recovery, which emphasizes the importance of the patient-provider relationship. PMID- 1429825 TI - The role of folates in the development of methotrexate resistance in human leukemia cell line K562. AB - The effect of reduced and oxidized folates on the development of methotrexate (MTX) resistance has been examined in human leukemia cell line K562 (K562/S). K562/S cells were made resistant to MTX by soft-agar cloning either in RPMI-1640 medium (K562/MTX-PGA) or in folic-acid-free RPMI-1640 medium containing 10 nM leucovorin (K562/MTX-LV). The optimal concentrations of leucovorin for the growth of K562/S, K562/MTX-PGA and K562/MTX-LV cells were 1 nM, 5 nM and 10 nM respectively. K562/MTX-PGA cells were 24-fold resistant to MTX as noted by impaired MTX transport. In contrast, K562/MTX-LV cells were 26-fold resistant to MTX as noted by gene amplification of dihydrofolate reductase. Furthermore cross resistance to cytosine arabinoside was only demonstrated in K562/MTX-PGA, while the K562/MTX-LV cells showed no significant cross-resistance to cytosine arabinoside. These results suggest that the type and level of folates used during the development of MTX resistance may play a role in the mechanism for MTX resistance. Leukemia cells that are grown in leucovorin might serve as a model for acquired MTX resistance in vivo. PMID- 1429826 TI - Effect of age on development of tumours in the intrasplenic ovarian grafts in ovariectomized rats. AB - Female rats at the age of 1, 3, and 14-16 months ("young", "adult" and "old" groups respectively) were bilaterally ovariectomized and one of the removed ovaries was autoimplanted into the spleen. The total intrasplenic ovarian tumour incidence was equal in the rats subjected to the operation at 3 and 14-16 months (77.4% and 80.6% respectively) and tumours developed more frequently in rats exposed to surgery at the age of 1 month (94.5%), P < 0.05. The incidence of Sertoli and Leydig cell tumours was increased and their latency was decreased in the old group in comparison to the adult one. In rats exposed to the operation at the age of 3 months, granulosotheca cell tumours developed more frequently than other tumour types, and in the young group thecomas were discovered more often than in both older groups. Dysgerminomas and luteomas were discovered only in intrasplenic grafts of rats of the young group. It is supposed that the differences in structure and proliferative activity of various ovarian tissues between young, adult and old rats at the moment of intrasplenic transplantation, as well as the differences in their response to gonadotropic stimulation play a significant role in the development of ovarian tumours of varied histogenesis in the intrasplenic ovarian grafts. PMID- 1429827 TI - Phase II trial of 5-fluorouracil, high-dose leucovorin calcium, and dipyridamole in advanced prostate cancer. AB - To examine the effect of altering intracellular folate pools on the efficacy of 5 fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300-370 mg m-2 day-1 x 5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m-2 day-1 x 5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6 h x 5.5 days) administered on a 28-day schedule in patients with stage D2 disease. A group of 13 patients have been treated. The median age was 68 years (range 48-78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D2 prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole. PMID- 1429828 TI - p53 point mutations in primary human gastric carcinomas. AB - p53 point mutations in primary gastric carcinomas were analyzed by performing cDNA deoxynucleotide sequencing of the gene. Out of 16, 9 (56.3%) primary gastric carcinoma cases, including early cancer, showed one or more p53 point mutations in their open-reading frame, and 4 out of 9 cases had a p53 point mutation within highly conserved domains. The characteristics of the p53 mutation spectrum observed in primary tumors were (a) frequent mutation at an A:T pair (50%, 7 out of 14 mutations), (b) high transversion incidence (29%, 4 out of 14 mutations), (c) no transition at CpG, and (d) no G:C to T:A transversion. Our results suggest that p53 mutation is a common event in gastric carcinoma occurring from the early stage of progression with its specific mutation spectrum. PMID- 1429829 TI - Neutron-capture therapy of murine ascites tumor with gadolinium-containing microcapsules. AB - Gadolinium-containing microcapsules were evaluated as an agent for gadolinium neutron-capture therapy. Mice were inoculated intraperitoneally with 10(7) Ehrlich ascites tumor cells and gadolinium microcapsules and exposed to thermal neutrons for 12 min (approximately 1.86 x 10(12) neutrons cm-2). Significantly more mice given gadolinium microcapsules than those given placebo microcapsules or control survived for 60 days and considerably longer (P < 0.0001), indicating that gadolinium neutron-capture reactions effectively suppressed the growth of ascites tumor cells in mice. The results suggest that these microcapsules are an effective gadolinium carrier for neutron-capture therapy. PMID- 1429831 TI - Investigations of droloxifene and other hormone manipulations on N nitrosomethylurea-induced rat mammary tumours. 1. Influence on tumour growth. AB - The effect of droloxifene, a new anti-oestrogenic drug, on N-nitrosomethylurea induced mammary tumours of Sprague-Dawley rats was investigated and compared with that of tamoxifen. The response of tumour growth to ovariectomy or to treatment with aminoglutethimide or high doses of oestradiol was also studied. Ovariectomy was by far the most effective treatment for mammary-tumour-bearing animals. More than 75% of the tumours in ovariectomized rats did not grow progressively but remained in remission for up to 12 weeks after castration when the experiment was terminated. The inhibitory effects of droloxifene and tamoxifen on mammary tumour growth were similar, but body weight loss of animals treated with tamoxifen was more marked than that of animals treated with droloxifene at the same dose and schedule. PMID- 1429830 TI - Drug resistance in oncology: from concepts to applications. AB - The complex problem of drug resistance is discussed with respect to host toxicity, to tumor characteristics (kinetic resistance, heterogeneity of cell subpopulations, hypoxia, mutation and gene amplification), and to the medication itself (pharmacokinetic and pharmacodynamic resistance: cell membrane, intracellular metabolism, intracellular target). After detailing each type of resistance, the possibilities of fighting against drug resistance are explored (dealing with host toxicity, tumor characteristics and drugs--intensifying therapy, multiple drug therapy, biochemical modulation, particular modalities of drug administration). Finally, perspectives of research and development of new drugs are summarized. PMID- 1429832 TI - Investigations of droloxifene and other hormonal manipulations on N nitrosomethylurea-induced rat mammary tumours. 2. Influence on oestrogen receptor. AB - In N-nitrosomethylurea-induced rat mammary tumours, tamoxifen is found to compete at the binding sites of the oestradiol receptor if a receptor determination is performed 1 day following the last drug application to animals. Despite a higher binding affinity of droloxifene (3-OH-tamoxifen) to oestradiol receptor, compared to tamoxifen, its influence on the measurable receptor quantity is only very weak or not demonstrable. Therefore, binding affinity is not a valid explanation for the different influences of the two anti-oestrogens on the receptor. These only can be attributed to different behaviour patterns of both substances in relation to their half-lives and metabolism and accumulation in the organism. Owing to the short half-life of droloxifene, even 1 day after the last application too little drug is available to compete for oestradiol binding sites. In the case of both anti-oestrogenic substances, cessation of drug application for 8 weeks abolished any influence on the oestradiol receptor. Furthermore, failure of aminoglutethimide to influence the oestradiol receptor could be observed because this substance does not act via this receptor. The experiments performed confirm literature data regarding the effect of aminoglutethimide therapy on oestradiol receptors in breast tumour tissue of human beings. In summary: receptor investigations of N-nitrosomethylurea-induced rat mammary tumours, used as a model to test therapy regimens with droloxifene or other drugs with a short half life, may be of limited value only. PMID- 1429833 TI - Pathway of incorporation of microinjected lamin A into the nuclear envelope. AB - When microinjected into the cytoplasm of 3T3 cells, biotinylated human lamin A rapidly enters the nucleus and gradually becomes incorporated into the nuclear lamina region as determined by immunofluorescence. The incorporation of the microinjected material takes several hours and progresses through a series of morphologically identifiable stages. Within minutes after microinjection, lamin A is found in spots distributed throughout the nucleus, except in nucleolar regions. Over a time course of up to 6 h, these spots appear to decrease in size and number as the biotinylated lamin A becomes associated with the endogenous nuclear lamina. Eventually, the typical nuclear rim staining pattern normally revealed by immunofluorescence with nuclear lamin antibodies is seen with antibiotin. This latter rim staining property is passed on to daughter cells following mitosis. These results indicate that the microinjected biotinylated nuclear lamin A retains those properties required for its integration into the lamina, as well as those necessary for the disassembly and subsequent reassembly of the nuclear lamina during cell division. The initial rapid accumulation into foci and the subsequent slower incorporation into the nuclear lamina appear to be analogous to the stages of incorporation following the microinjection of cytoskeletal intermediate filament proteins such as vimentin and keratin (Vikstrom, K., G. G. Borisy, and R. D. Goldman. 1989. Proc. Natl. Acad. Sci. USA. 86:549-553; Miller, R. K., K. Vikstrom, and R. D. Goldman. 1991. J. Cell Biol. 113:843-855). Foci are also observed in some uninjected cells using nuclear lamin antibodies, indicating that these features are a genuine component of nuclear substructure. Evidence is presented that shows the appearance of these nuclear structures is cell cycle dependent. PMID- 1429834 TI - NOP3 is an essential yeast protein which is required for pre-rRNA processing. AB - The four nucleolar proteins NOP1, SSB1, GAR1, and NSR1 of Saccharomyces cerevisiae share a repetitive domain composed of repeat units rich in glycine and arginine (GAR domain). We have cloned and sequenced a fifth member of this family, NOP3, and shown it to be essential for cell viability. The NOP3 open reading frame encodes a 415 amino acid protein with a predicted molecular mass of 45 kD, containing a GAR domain and an RNA recognition motif. NOP3-specific antibodies recognize a 60-kD protein by SDS-PAGE and decorate the nucleolus and the surrounding nucleoplasm. A conditional lethal mutation, GAL::nop3, was constructed; growth of the mutant strain in glucose medium represses NOP3 expression. In cells depleted of NOP3, production of cytoplasmic ribosomes is impaired. Northern analysis and pulse-chase labeling indicate that pre-rRNA processing is inhibited at the late steps, in which 27SB pre-rRNA is cleaved to 25S rRNA and 20S pre-rRNA to 18S rRNA. PMID- 1429835 TI - GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex. AB - We have examined the role of ras-related rab proteins in transport from the ER to the Golgi complex in vivo using a vaccinia recombinant T7 RNA polymerase virus to express site-directed rab mutants. These mutations are within highly conserved domains involved in guanine nucleotide binding and hydrolysis found in ras and all members of the ras superfamily. Substitutions in the GTP-binding domains of rab1a and rab1b (equivalent to the ras 17N and 116I mutants) resulted in proteins which were potent trans dominant inhibitors of vesicular stomatitis virus glycoprotein (VSV-G protein) transport between the ER and cis Golgi complex. Immunofluorescence analysis indicated that expression of rab1b121I prevented delivery of VSV-G protein to the Golgi stack, which resulted in VSV-G protein accumulation in pre-Golgi punctate structures. Mutants in guanine nucleotide exchange or hydrolysis of the rab2 protein were also strong trans dominant transport inhibitors. Analogous mutations in rab3a, rab5, rab6, and H-ras did not inhibit processing of VSV-G to the complex, sialic acid containing form diagnostic of transport to the trans Golgi compartment. We suggest that at least three members of the rab family (rab1a, rab1b, and rab2) use GTP hydrolysis to regulate components of the transport machinery involved in vesicle traffic between early compartments of the secretory pathway. PMID- 1429836 TI - The VPS1 protein, a homolog of dynamin required for vacuolar protein sorting in Saccharomyces cerevisiae, is a GTPase with two functionally separable domains. AB - The product of the VPS1 gene, Vps1p, is required for the sorting of soluble vacuolar proteins in the yeast Saccharomyces cerevisiae. We demonstrate here that Vps1p, which contains a consensus tripartite motif for guanine nucleotide binding, is capable of binding and hydrolyzing GTP. Vps1p is a member of a subfamily of large GTP-binding proteins whose members include the vertebrate Mx proteins, the yeast MGM1 protein, the Drosophila melanogaster shibire protein, and dynamin, a bovine brain protein that bundles microtubules in vitro. Disruption of microtubules did not affect the fidelity or kinetics of vacuolar protein sorting, indicating that Vps1p function is not dependent on microtubules. Based on mutational analyses, we propose a two-domain model for Vps1p function. When VPS1 was treated with hydroxylamine, half of all mutations isolated were found to be dominant negative with respect to vacuolar protein sorting. All of the dominant-negative mutations analyzed further mapped to the amino-terminal half of Vps1p and gave rise to full-length protein products. In contrast, recessive mutations gave rise to truncated or unstable protein products. Two large deletion mutations in VPS1 were created to further investigate Vps1p function. A mutant form of Vps1p lacking the carboxy-terminal half of the protein retained the capacity to bind GTP and did not interfere with sorting in a wild type background. A mutant form of Vps1p lacking the entire GTP-binding domain interfered with vacuolar protein sorting in wild-type cells. We suggest that the amino-terminal domain of Vps1p provides a GTP-binding and hydrolyzing activity required for vacuolar protein sorting, and the carboxy-terminal domain mediates Vps1p association with an as yet unidentified component of the sorting apparatus. PMID- 1429837 TI - Localization of dystrophin gene transcripts during mouse embryogenesis. AB - The spatial and temporal expression of the dystrophin gene has been examined during mouse embryogenesis, using in situ hybridization on tissue sections with a probe from the 5' end of the dystrophin coding sequence. In striated muscle, dystrophin transcripts are detectable from about 9 d in the heart and slightly later in skeletal muscle. However, there is an important difference between the two types of muscle: the heart is already functional as a contractile organ before the appearance of dystrophin transcripts, whereas this is not the case in skeletal muscle, where dystrophin and myosin heavy chain transcripts are first detectable at the same time. In the heart, dystrophin transcripts accumulate initially in the outflow tract and, at later stages, in both the atria and ventricles. In skeletal muscle, the gene is expressed in all myocytes irrespective of fiber type. In smooth muscle dystrophin transcripts are first detectable from 11 d post coitum in blood vessels, and subsequently in lung bronchi and in the digestive tract. The other major tissue where the dystrophin gene is expressed is the brain, where transcripts are clearly detectable in the cerebellum from 13 d. High-level expression of the gene is also seen in particular regions of the forebrain involved in the regulation of circadian rhythms, the endocrine system, and olfactory function, not previously identified in this context. The findings are discussed in the context of the pathology of Duchenne muscular dystrophy. PMID- 1429838 TI - An unconventional myosin heavy chain gene from Drosophila melanogaster. AB - As part of a study of cytoskeletal proteins involved in Drosophila embryonic development, we have undertaken the molecular analysis of a 140-kD ATP-sensitive actin-binding protein (Miller, K. G., C. M. Field, and B. M. Alberts. 1989. J. Cell Biol. 109:2963-2975). Analysis of cDNA clones encoding this protein revealed that it represents a new class of unconventional myosin heavy chains. The amino terminal two thirds of the protein comprises a head domain that is 29-33% identical (60-65% similar) to other myosin heads, and contains ATP-binding, actin binding and calmodulin/myosin light chain-binding motifs. The carboxy-terminal tail has no significant similarity to other known myosin tails, but does contain a approximately 100-amino acid region that is predicted to form an alpha-helical coiled-coil. Since the unique gene that encodes this protein maps to the polytene map position 95F, we have named the new gene Drosophila 95F myosin heavy chain (95F MHC). The expression profile of the 95F MHC gene is complex. Examination of multiple cDNAs reveals that transcripts are alternatively spliced and encode at least three protein isoforms; in addition, a fourth isoform is detected on Western blots. Developmental Northern and Western blots show that transcripts and protein are present throughout the life cycle, with peak expression occurring during mid-embryogenesis and adulthood. Immunolocalization in early embryos demonstrates that the protein is primarily located in a punctate pattern throughout the peripheral cytoplasm. Most cells maintain a low level of protein expression throughout embryogenesis, but specific tissues appear to contain more protein. We speculate that the 95F MHC protein isoforms are involved in multiple dynamic processes during Drosophila development. PMID- 1429840 TI - Host cell factors controlling vimentin organization in the Xenopus oocyte. AB - To study vimentin filament organization in vivo we injected Xenopus oocytes, which have no significant vimentin system of their own, with in vitro-synthesized RNAs encoding Xenopus vimentins. Exogenous vimentins were localized primarily to the cytoplasmic surface of the nucleus and to the subplasma membrane "cortex." In the cortex of the animal hemisphere, wild-type vimentin forms punctate structures and short filaments. In contrast, long anastomosing vimentin filaments are formed in the vegetal hemisphere cortex. This asymmetry in the organization of exogenous vimentin is similar to that of the endogenous keratin system (Klymkowsky, M. W., L. A. Maynell, and A. G. Polson. 1987. Development (Camb.). 100:543-557), which suggests that the same cellular factors are responsible for both. Before germinal vesicle breakdown, in the initial stage of oocyte maturation, large vimentin and keratin filament bundles appear in the animal hemisphere. As maturation proceeds, keratin filaments fragment into soluble oligomers (Klymkowsky, M. W., L. A. Maynell, and C. Nislow. 1991. J. Cell Biol. 114:787-797), while vimentin filaments remain intact and vimentin is hyperphosphorylated. To examine the role of MPF kinase in the M-phase reorganization of vimentin we deleted the conserved proline of vimentin's single MPF-kinase site; this mutation had no apparent effect on the prophase or M-phase behavior of vimentin. In contrast, deletion of amino acids 19-68 or 18-61 of the NH2-terminal "head" domain produced proteins that formed extended filaments in the animal hemisphere of the prophase oocyte. We suggest that the animal hemisphere cortex of the prophase oocyte contains a factor that actively suppresses the formation of extended vimentin filaments through a direct interaction with vimentin's head domain. During maturation this "suppressor of extended filaments" appears to be inactivated, leading to the formation of an extended vimentin filament system. PMID- 1429841 TI - Newly assembled microtubules are concentrated in the proximal and distal regions of growing axons. AB - We have investigated the sites of microtubule (MT) assembly in neurons during axon growth by taking advantage of the relationship between the proportion of tyrosinated alpha-tubulin (tyr-tubulin) in MTs and their age. Specifically, young (newly assembled) MTs contain more tyr-tubulin than older (more long-lived) MTs. To quantify the relative proportion of tyr-tubulin in MTs, cultured rat sympathetic neurons were permeabilized under conditions that stabilize existing MTs and remove unassembled tubulin. The MTs were then double-stained with antibodies to tyr-tubulin (as a measure of the amount of tyr-tubulin in MTs) and to beta-tubulin (as a measure of total MT mass), using immunofluorescence procedures. Cells were imaged with a cooled charge-coupled device camera and the relative proportion of tyr-tubulin in the MTs was quantified by computing the ratio of the tyr-tubulin fluorescence to the beta-tubulin fluorescence using a novel application of digital image processing and analysis techniques. The amount of tyr-tubulin in the MTs was highest in the cell body and at the growth cone; peak ratios in these two regions were approximately 10-fold higher than for the axon shaft. Moving out from the cell body into the axon, the tyr-tubulin content declined over an average distance of 40 microns to reach a constant low value within the axon shaft and then rose again more distally, over an average distance of 110 microns, to reach a peak at the growth cone (average axon length = 358 microns). These observations indicate that newly assembled MTs are concentrated in the proximal and distal regions of growing axons and therefore that the cell body and growth cone are the most active sites of MT assembly dynamics in neurons that are actively extending axons. PMID- 1429839 TI - A 62-kD protein required for mitotic progression is associated with the mitotic apparatus during M-phase and with the nucleus during interphase. AB - A protein of 62 kD is a substrate of a calcium/calmodulin-dependent protein kinase, and both proteins copurify with isolated mitotic apparatuses (Dinsmore, J. H., and R. D. Sloboda. 1988. Cell. 53:769-780). Phosphorylation of the 62-kD protein increases after fertilization; maximum incorporation of phosphate occurs during late metaphase and anaphase and correlates directly with microtubule disassembly as determined by in vitro experiments with isolated mitotic apparatuses. Because 62-kD protein phosphorylation occurs in a pattern similar to the accumulation of the mitotic cyclin proteins, experiments were performed to determine the relationship between cyclin and the 62-kD protein. Continuous labeling of marine embryos with [35S]methionine, as well as immunoblots of marine embryo proteins using specific antibodies, were used to identify both cyclin and the 62-kD protein. These results clearly demonstrate that the 62-kD protein is distinct from cyclin and, unlike cyclin, is a constant member of the cellular protein pool during the first two cell cycles in sea urchin and surf clam embryos. Similar results were obtained using immunofluorescence microscopy of intact eggs and embryos. In addition, immunogold electron microscopy reveals that the 62-kD protein associates with the microtubules of the mitotic apparatus in dividing cells. Interestingly, the protein changes its subcellular distribution with respect to microtubules during the cell cycle. Specifically, during mitosis the 62-kD protein associates with the mitotic apparatus; before nuclear envelope breakdown, however, the 62-kD protein is confined to the nucleus. After anaphase, the 62-kD protein returns to the nucleus, where it resides until nuclear envelope disassembly of the next cell cycle. PMID- 1429842 TI - Calcium influx into neurons can solely account for cell contact-dependent neurite outgrowth stimulated by transfected L1. AB - We have used monolayers of control 3T3 cells and 3T3 cells expressing transfected human L1 as a culture substrate for rat PC12 cells and rat cerebellar neurons. PC12 cells and cerebellar neurons extended longer neurites on human L1 expressing cells. Neurons isolated from the cerebellum at postnatal day 9 responded equally as well as those isolated at postnatal day 1-4, and this contrasts with the failure of these older neurons to respond to the transfected human neural cell adhesion molecule (NCAM). Human L1-dependent neurite outgrowth could be blocked by antibodies that bound to rat L1 and, additionally, the response could be fully inhibited by pertussis toxin and substantially inhibited by antagonists of L- and N-type calcium channels. Calcium influx into neurons induced by K+ depolarization fully mimics the L1 response. Furthermore, we show that L1- and K+(-)dependent neurite outgrowth can be specifically inhibited by a reduction in extracellular calcium to 0.25 microM, and by pretreatment of cerebellar neurons with the intracellular calcium chelator BAPTA/AM. In contrast, the response was not inhibited by heparin or by removal of polysialic acid from neuronal NCAM both of which substantially inhibit NCAM-dependent neurite outgrowth. These data demonstrate that whereas NCAM and L1 promote neurite outgrowth via activation of a common CAM-specific second messenger pathway in neurons, neuronal responsiveness to NCAM and L1 is not coordinately regulated via posttranslational processing of NCAM. The fact that NCAM- and L1-dependent neurite outgrowth, but not adhesion, are calcium dependent provides further evidence that adhesion per se does not directly contribute to neurite outgrowth. PMID- 1429844 TI - Thyroid hormone, insulin, and glucocorticoids are sufficient to support chondrocyte differentiation to hypertrophy: a serum-free analysis. AB - Chondrocytes from chicken embryo tibia can be maintained in culture as adherent cells in Coon's modified Ham's F-12 medium supplemented with 10% FCS. In this condition, they dedifferentiate, losing type II collagen expression in favor of type I collagen synthesis. Their differentiation to hypertrophy can be obtained by transferring them to suspension culture. Differentiation is evidenced by the shift from type I to type II and type IX collagen synthesis and the following predominant expression of type X collagen, all markers of specific stages of the differentiation process. To identify the factors required for differentiation, we developed a serum-free culture system where only the addition of triiodothyronine (T3; 10(-11) M), insulin (60 ng/ml), and dexamethasone (10(-9) M) to the F-12 medium was sufficient to obtain hypertrophic chondrocytes. In this hormonal context, chondrocytes display the same changes in the pattern of protein synthesis as described above. For proper and complete cell maturation, T3 and insulin concentrations cannot be modified. Insulin cannot be substituted by insulin-like growth factor-I, but dexamethasone concentration can be decreased to 10(-12) M without chondrogenesis being impaired. In the latter case, the expression of type X collagen and its mRNA are inversely proportional to dexamethasone concentration. When ascorbic acid is added to the hormone supplemented medium, differentiating chondrocytes organize their matrix leading to a cartilage-like structure with hypertrophic chondrocytes embedded in lacunae. However, this structure does not present detectable calcification, at variance with control cultures maintained in FCS. Accordingly, in the presence of the hormone mixture, the differentiating chondrocytes have low levels of alkaline phosphatase activity. This report indicates that T3 and insulin are primary factors involved in the onset and progression of chondrogenesis, while dexamethasone supports cell viability and modulates some differentiated functions. PMID- 1429843 TI - Laminin in the male germ cells of Drosophila. AB - To study genes that may be crucial for the male germ cell development of Drosophila we screened a cDNA expression library with a polyclonal antiserum against testis proteins of Drosophila hydei. We identified a cDNA fragment that exhibited a complete sequence similarity with the cDNA of the laminin B2 chain, an important component of the extracellular matrix. Transcripts of laminin B2 were detected in the RNA of male germ cells with the polymerase chain reaction and by in situ hybridization. We studied the reaction of different polyclonal antibodies including those against a Drosophila laminin B2-lac fusion protein, the entire Drosophila laminin complex, or against the mouse laminin complex and against laminin A and B1 chains with specific structures in developing male germ cells of Drosophila. Antigenic sites against laminin B2 were found in the lampbrush loops in primary spermatocyte nuclei, in nuclei of spermatids, and in heads of spermatozoa. The axonemes of elongating spermatids react with antibodies against the Drosophila laminin B1, B2 and laminin A chains. The possible biological functions of the laminin in the male germ cells of Drosophila are discussed. PMID- 1429845 TI - The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis. AB - We have cloned from a mouse placenta cDNA library a mouse homologue of the human stromelysin-3 (ST3) cDNA, which codes for a putative matrix metalloproteinase expressed in breast carcinomas. The ST3 protein is well conserved between humans and mice, and the pattern of ST3 gene expression is similar in both species, and shows expression in the placenta, in the uterus, and during limb bud morphogenesis. We show that the ST3 gene can also be expressed in the normal mouse mammary gland. ST3 gene expression was not detected during mammary growth, neither in virgin nor in pregnant mice, but was specifically observed during postlactating involution of the gland, an apoptotic process associated with intense extracellular matrix remodeling. ST3 transcripts were found in fibroblasts immediately surrounding degenerative ducts, suggesting that ST3 gene expression may be associated with the basement membrane dissolution, which occurs during mammary gland involution. Since the ST3 gene is also specifically expressed in fibroblastic cells surrounding invasive neoplastic cells of breast carcinomas, we suggest that ST3 is implicated in extracellular matrix remodeling processes common to mammary apoptosis and breast cancer progression. PMID- 1429846 TI - Norepinephrine stimulates the direct breakdown of phosphatidyl inositol in rat tail artery. AB - When segments of rat tail artery were labeled with [3H]inositol and then stimulated with norepinephrine (NE), the inositol phosphates produced were primarily IP and IP2, together with a small but significant amount of Ins(1,4,5)P3 and a very small amount of Ins(1,3,4,5)P4. It has been unclear in many studies whether or not the relatively large levels of IP and IP2 produced in [3H]inositol-labeled tissue represent indirect products of phosphatidyl inositol(4,5)bis phosphate breakdown (through Ins(1,4,5)P3) or direct products of phosphatidyl inositol 4 monophosphate and phosphatidyl inositol breakdown. In order to answer this question tail artery segments were prelabeled with [3H]inositol and then permeabilized with beta escin and stimulated with norepinephrine and GTP gamma S, so that increases in IP, IP2, and Ins(1,4,5)P3 were still observed. If these permeable segments were stimulated with agonist in the presence of compounds known to inhibit Ins(1,4,5)P3 5-phosphatase, such as glucose 6P, (2,3)diphosphoglycerate, or Ins(1,4,5)P3, the levels of labeled Ins(1,4,5)P3 and labeled IP2 were increased, while the level of stimulated labeled IP was unchanged. This indicated that some of the IP2 and IP formed in these cells was produced from PIP2 but that some of these compounds might be formed from PIP or PI. When the isomers of inositol monophosphate, Ins 1P and Ins 4P, were separated by HPLC, it was shown that after prelabeled tail artery was stimulated by norepinephrine for periods of 1-2 min, the predominant isomer formed was Ins 4P, indicating either PIP2 or PIP as the source. However, after 5 20 min stimulation, both Ins 1P and Ins 4P were formed in equal amounts, suggesting that during sustained stimulation of smooth muscle PI itself was broken down directly. Therefore it appears that within 1-2 min of norepinephrine addition to vascular smooth muscle the bulk of the IP and IP2 produced are derived from PIP2 via IP3, while after 20 min of norepinephrine treatment much of the IP comes directly from PI. This suggests that the regulation of PLC in this tissue is more complicated than has been previously believed. PMID- 1429848 TI - Cellular and molecular regulation of factor V expression in human megakaryocytes. AB - The mechanisms responsible for regulating FV expression in normal human megakaryocytes are unknown. To test the hypothesis that they are related to cell maturation events, we correlated human megakaryocyte FV antigen content with several putative maturation markers including cell size, morphologic stage of development, and ploidy level. Mature megakaryocytes were isolated from normal marrow by counterflow centrifugal elutriation. The cells were immunofluorescently labeled with a monoclonal antibody probe (B10) directed against the FV connecting peptide (150 kDa) and then reacted with Chromomycin A3 to allow for simultaneous DNA quantitation in the same cell. After processing, individual cells were stages and sized. FV antigen and nuclear DNA levels (ploidy) were measured by microphotometric measurements of total cytoplasmic or nuclear fluorescence. A total of 1,006 cells were examined, of which 12% were stage I, 8% were stage II, 35% were stage III, and 45% were stage IV. The geometric mean diameter (+/- SD) of cells in these stages was 48.3 +/- 11.8 microns2, 54.9 +/- 14.4 microns2, 61.7 +/- 20.02 microns2, and 56.7 +/- 13.2 microns2, respectively. Respective ploidy values in arbitrary fluorescence units, where 2 N = 5%, were 28.2 +/- 18.2%, 31.4 +/- 19.3%, 54.3 +/- 26.6%, and 33.2 +/- 22.7%. Calculated correlation coefficients (r) and coefficient of determination (r2) values suggested that FV antigen levels varied independently of any of the maturation markers studied. However, FV antigen levels could be upregulated by 24 h exposure to 8 nM phorbol myristate acetate (PMA). Presence of FV mRNA in a pure population of megakaryocytes was demonstrated by in situ hybridization and the polymerase chain reaction. Relative levels of megakaryocyte FV mRNA, as assessed by in situ hybridization, failed to reveal a detectable change after PMA exposure in spite of an increase in detectable protein. These data suggest that FV synthesis may be regulated at the post-transcriptional level and that it is subject to regulatory influences which are not coordinately linked to development of other terminal maturation markers. PMID- 1429847 TI - Growth on type I collagen promotes expression of the osteoblastic phenotype in human osteosarcoma MG-63 cells. AB - Using MG-63 cells as a model system capable of partial osteoblastic differentiation, we have examined the effect of growth on extracellular matrix. MG-63 cell matrix and purified type I collagen induced a morphological change characterized by long cytoplasmic processes reminiscent of those seen in osteocytes. Concurrent biochemical changes involving bone marker proteins included increased specific activity of cell-associated alkaline phosphatase and increased secretion of osteonectin (up to 2.5-fold for each protein); all changes occurred without alterations in the growth kinetics of the MG-63 cells. The increase in alkaline phosphatase activity was maximal on days 6-8 following seeding; increased osteonectin secretion was most prominent immediately following seeding; all changes decreased as cells reached confluence. Growing cells on type I collagen resulted in an increased induction of alkaline phosphatase activity by 1,25(OH)2D3 (with little change in the 1,25(OH)2D3 induction of osteonectin and osteocalcin secretion), and increased TGF-beta induction of alkaline phosphatase activity as well (both TGF-beta 1 and TGF-beta 2). Both the 1,25(OH)2D3 and TGF beta effects appeared to be synergistic with growth on type I collagen. These studies support the hypothesis that bone extracellular matrix may play an important role in osteoblastic differentiation and phenotypic expression. PMID- 1429849 TI - Differential regulation of glucose transporter 1 and 2 mRNA expression by epidermal growth factor and transforming growth factor-beta in rat hepatocytes. AB - We have examined by Northern blot analysis the expression of two members of the glucose transporter family of genes (GLUT-1 and GLUT-2) in regenerating liver and in hepatocytes cultured under various conditions. GLUT-1, although thought to be a growth-associated gene, is not expressed in normal or regenerating liver, whereas GLUT-2, a liver-specific gene, is abundant in normal liver and gradually up-regulated during liver regeneration. Conversely, in hepatocytes cultured conventionally on dried rat tail collagen (RTC) in the presence of EGF and insulin, which potentiate proliferation, GLUT-1 mRNA is rapidly and abundantly expressed, whereas GLUT-2 is depressed. To investigate the causes of this "switch" in glucose transporter expression seen when hepatocytes are removed from the liver and cultured under the conventional proliferative conditions, we examined the effects of specific growth factors and extracellular matrices on cultured hepatocytes. EGF, a potent liver mitogen, although causing a threefold induction of GLUT-1, was found to have no effect on GLUT-2 expression, suggesting that the increase in GLUT-2 seen in regenerating liver is not due to EGF. Inhibition of protein synthesis by cycloheximide in cultured hepatocytes does not prevent the induction of GLUT-1 mRNA. In addition, treatment of cells with cycloheximide appears to stabilize the GLUT-2 mRNA, preventing the usual down regulation of this gene in cultured hepatocytes. The expression of the two glucose transporter mRNAs also differed when the hepatocytes were adherent to particular cell matrices. Culture of hepatocytes on a reconstituted basement membrane gel matrix (EHS) is known to restrain their growth and mediate high levels of differentiated hepatocytic functions that are lost under conventional culture conditions. Unlike cells on RTC, hepatocytes on EHS expressed low levels of GLUT-1 mRNA, and decreased GLUT-2 mRNA. TGF-beta, an attenuator of DNA synthesis, when added to cultures on RTC, substantially down-regulated GLUT-2 but had no effect on GLUT-1. We propose that the effectors, EGF, TGF-beta and basement membrane components, play a significant role in the regulation of expression of GLUT-1 and GLUT-2 in hepatocytes. PMID- 1429850 TI - Methylation of atypical protein aspartyl residues during the stress response of HeLa cells. AB - A protein carboxyl methyltransferase (PCMT), which specifically modifies atypical protein L-isoaspartyl and D-aspartyl residues, is widely distributed in eucaryotic cells, but the factors that regulate its activity in vivo have not been identified. It has been proposed that the PCMT initiates the repair of structurally damaged proteins. To test the possibility that the concentration of structurally abnormal cellular proteins affects PCMT activity, protein carboxyl methylation reactions were studied in HeLa cells exposed to various stresses that increase the extent of protein unfolding in cells. Protein carboxyl methylation rates increased 70-80% during incubations at 42 degrees C and remained elevated for periods of up to 8 hr. This sustained increase was greater than that predicted from thermal effects on the enzyme alone and may reflect the exposure of atypical aspartyl sites as proteins unfold as well as increased rates of protein deamidation and isomerization at elevated temperatures. Methylation rates showed no increases following 12 hr incubations with the amino acid analogs L azetidine-2-carboxylic acid or L-canavanine. Northern blot analysis of RNA preparations from control and stressed cells revealed three major transcripts for the PCMT in HeLa cells, which are 1.6, 2.6, and 4.5 kb in length. The concentrations of all three transcripts decreased by approximately 20% from control levels during heat shock. No changes in PCMT transcript concentrations were observed during incubation with the amino acid analogs. By contrast, large increases in the concentrations of hsp70 and ubiquitin transcripts were observed following either heat or chemical stresses. The results demonstrate that the PCMT is a constitutive component of cells whose function is required under normal conditions as well as during stress conditions, which accelerate structural damage to cellular proteins. PMID- 1429851 TI - Leukemia inhibitory factor and interleukin-11 promote maturation of murine and human megakaryocytes in vitro. AB - The growth-promoting activities of optimally stimulating concentrations of leukemia inhibitory factor (LIF) and interleukin-11 (IL-11), a stromal cell derived cytokine, on megakaryocytes in liquid marrow cultures were compared to interleukin-6 (IL-6), a known megakaryocytes maturation factor. Maximally stimulating concentrations of LIF (25 ng/ml), IL-11 (10 ng/ml), or IL-6 alone (10 ng/ml) promoted an 81, 157, and 153% increase, respectively, in acetylcholinesterase (AchE) activity in murine serum-free cultures compared with controls (n = 5). In combination with 25 U/ml murine interleukin-3 (IL-3), LIF, IL-6, and IL-11 showed increases, respectively, of 35%, 49%, and 174% in AchE activity compared with IL-3 alone (n = 4). Flow cytometric analysis of 4-day-old cultures showed that LIF alone had minimal effect on megakaryocytic ploidy, whereas IL-11 and IL-6 alone markedly augmented high ploidy cells. Enumeration of cells stained for AchE showed that IL-11 increased the numbers of Mks in comparison to LIF, IL-6 or controls by up to 59%. Moreover, a twofold increment in Mk number was noted when IL-11 was used in combination with IL-3 (compared with either IL-3 alone of IL-3+IL-6). Flow cytometric ploidy analysis of 8-day old human liquid marrow cultures showed that either LIF, IL-11, or IL-6 alone markedly augmented the percentage of 32N cells compared with cultures containing only human IL-3. The data suggest that LIF and IL-11 promote murine and human Mk maturation in vitro, although the effect of IL-11 exceeds that of LIF in mice. Despite the comparable influence of IL-11 and IL-6 on Mk ploidy, IL-11 has the additional characteristic of enhancing the number of Mks, particularly in combination with IL-3. PMID- 1429852 TI - Effect of L-fucose on proliferation and myo-inositol metabolism in cultured cerebral microvessel and aortic endothelial cells. AB - Decreased myo-inositol metabolism possibly contributes to the development of diabetic complications including micro and macrovascular disease. Previous studies have shown that hyperglycemia may be partially responsible for this defect. We have found that L-fucose, a monosaccharide present in low concentrations in normal circulation and found to be elevated in diabetes, causes defects in cultured endothelial cells, including alterations in myo-inositol metabolism and proliferation. Murine cerebral microvessel and bovine aortic endothelial cells take up L-fucose from the medium in a time and concentration dependent manner. Both acute and chronic exposure of these cultured endothelial cells to media containing L-fucose at concentrations that may exist in diabetic sera cause a significant decrease in the accumulation of myo-inositol and its incorporation into inositol phospholipids. There is a concomitant decrease in the intracellular levels of myo-inositol. Kinetic analysis of the effect of L-fucose on myo-inositol uptake suggests that L-fucose competitively inhibits the transport of myo-inositol, exhibiting a Ki in the range of 1.6-4.1 mM for both cell types. Endothelial cells exposed to L-fucose concentrations of 0.5-20 mM exhibit depressed rates of proliferation in a concentration-dependent fashion. Furthermore, L-fucose causes a concentration-dependent decrease in synthesis of proteoglycan by cultured cerebral microvessel endothelial cells as measured by incorporation of 35S; however, this effect is not observed in the aortic endothelia. These data suggest that L-fucose at concentrations that may exist in diabetic sera may impair myo-inositol metabolism and proliferation of the vascular endothelium. PMID- 1429853 TI - Hepatocyte growth factor induces calcium mobilization and inositol phosphate production in rat hepatocytes. AB - The effects of hepatocyte growth factor (HGF) on intracellular Ca2+ mobilization were studied using fura-2-loaded single rat hepatocytes. Hepatocytes microperfused with different amounts of HGF responded with a rapid concentration dependent rise in the cytosolic free Ca2+ concentration with a maximum increase of 142% at 80 ng/ml of HGF. The lag period of the Ca2+ response was decreased with increasing HGF concentrations, being 64 +/- 12 s, 42 +/- 6 s, and 14 +/- 2 s, respectively, with 8, 20, and 80 ng/ml of HGF. The detailed pattern of Ca2+ transients, however, was variable. Out of 16 cells tested using 20 ng/ml of HGF, 68% showed sustained oscillatory responses, whereas other cells showed a sustained increase in the cytosolic-free Ca2+ upon exposure to HGF, which was dependent on the presence of extracellular Ca2+. HGF also induced Ca2+ entry across the plasma membrane. Mobilization of Ca2+ by HGF was accompanied by a rapid accumulation of inositol 1,4,5-trisphosphate (Ins 1,4,5-P3). The effects of HGF and epidermal growth factor (EGF) were comparable and partly additive for Ins 1,4,5-P3 production and for the sustained phase of Ca2+ mobilization. Preincubation of cells with 10 microM of genistein to inhibit protein tyrosine kinases abolished the HGF-induced Ca2+ response and also inhibited HGF-induced Ins 1,4,5-P3 production in rat liver cells. These data indicate that early events in the signal transduction pathways mediated by HGF and EGF have in common the requirements for tyrosine kinase activity, Ins 1,4,5-P3 production, and Ca2+ mobilization. PMID- 1429854 TI - Different organizational states of fodrin in cultured MDCK cells are induced by treatment with low pH, calmodulin antagonist TFP, and tumor promoter PMA. AB - We have investigated the molecular mechanisms underlying dynamic organization of the fodrin network by treating the epithelial MDCK cells with various agents affecting intracellular pH, intracellular calcium ion concentration, intracellular calmodulin, and protein kinase C (PKC) activity. Elevation of intracellular calcium level by A23187 or treatment with trifluoperazine (TFP), a calmodulin inhibitor, did not have any drastic effect on the fodrin distribution as judged by immunofluorescence microscopy. A long-term incubation with phorbol 12-myristate-13-acetate (PMA), a protein kinase C activator, in contrast, released fodrin from the lateral walls of the MDCK cells, leading to a diffuse cytoplasmic distribution. TFP, along with PMA, accelerated destabilization of the fodrin skeleton. Treatment with TFP alone rapidly released the cells from the substratum, which, however, could be prevented by PMA. We have previously shown that lowering of intracellular pH (< 6.5) leads to a removal of fodrin from its basolateral residence (Eskelinen et al., 1992) and that this translocation is reversed upon returning normal pH. We now show that the rebuilding of the membrane skeleton can be prevented if TFP is added to the acidified cells. Moreover, in TFP-treated acidified cells, fodrin shows a clusterlike organization similar to that observed in resting lymphocytes. We also noticed that interconversions between these different organizational states of fodrin are independent of the intracellular calcium concentration. Thus manipulation of the intracellular pH and treatment with TFP and PMA reveals different organizational states of the fodrin skeleton. This suggests that fodrin may participate in PMA-, TFP- and pH-sensitive signal transduction pathways. PMID- 1429855 TI - Constitutive HSP70: oligomerization and its dependence on ATP binding. AB - The constitutive HSP70 purified from CHO cells, which indicated a single band in SDS-polyacrylamide gel electrophoresis, showed multiple bands in native polyacrylamide gel electrophoresis. These results indicate that the protein may exist in oligomeric forms. After crosslinking the oligomers with glutaraldehyde, SDS-polyacrylamide gel electrophoresis showed three protein bands of molecular weight 70 kDa, 153 kDa, and 200 kDa corresponded to monomer, dimer, and trimer, respectively. The relative amount of oligomeric forms was dependent upon ATP concentrations: it increased upon hydrolysis of ATP or decreased upon incubation with high concentrations of ATP (1-10 mM). Autoradiographic analysis of the native polyacrylamide gel electrophoresis of HSP70 following incubation with [gamma-32P]ATP revealed that ATP bound to only monomer. These results suggest that the equilibrium between oligomeric forms is dependent on ATP concentrations. Nonetheless, during heat shock, both monomer and oligomer might be indistinguishably associated with some proteins, probably denatured proteins. PMID- 1429856 TI - Growth factors produced by human embryonic kidney cells that influence megakaryopoiesis include erythropoietin, interleukin 6, and transforming growth factor-beta. AB - Partially purified protein preparations containing megakaryocyte growth factor activity were prepared from human embryonic kidney (HEK) cell conditioned medium using ammonium sulfate precipitation, Cibicron blue affinity chromatography, and wheatgerm lectin affinity chromatography. Treatment of these preparations with neutralizing antibodies directed against erythropoietin (EPO) and interleukin 6 (IL6) resulted in a dramatic reduction in their capacity to stimulate megakaryocyte maturation in vitro. The presence of EPO in these preparations was confirmed by both immunoblotting and use of a mouse spleen erythroid progenitor cell proliferation assay routinely used to quantitate EPO activity in vitro. Northern blot analysis of HEK cell-derived mRNA with IL6 DNA probes revealed the presence of an IL6 transcript with a molecular size of 1.3 kb. Analysis of the HEK cell-derived preparation by ELISA confirmed the presence of immunologically reactive IL6. In addition, it was shown that purified recombinant human EPO and IL6 stimulated megakaryocyte maturation in the in vitro assay used in this study. These data indicate that the activity in HEK cell conditioned medium that stimulates megakaryocyte maturation in vitro is predominantly due to the presence of IL6 and EPO. Immunoneutralization studies of another HEK cell-derived preparation, which was inhibitory in the megakaryocyte maturation assay, demonstrated that it contained transforming growth factor beta (TGF beta), a potent inhibitor of megakaryocyte maturation. Taken together, these studies indicate that HEK cell conditioned medium, which has previously been reported to contain megakaryocyte growth factor activity, is comprised of a complex mixture of growth and differentiation factors, some of which promote and others that inhibit the process of megakaryopoiesis. PMID- 1429857 TI - Transformed growth phenotype of mouse mammary epithelium in primary culture induced by specific fetal mesenchymes. AB - When mesenchyme from fetal mammary or salivary gland is implanted into adult mouse mammary gland, adjacent epithelium responds with intense hyperplasia. The hyperplastic cells are more vulnerable than are non-stimulated cells to transformation in vivo by a chemical carcinogen or by mammary tumor virus. This system provides a potentially useful model for determining how stroma contributes to mammary tumorigenesis. We have developed co-culture systems and used them to investigate in more detail the nature of the signal produced by the mesenchyme cells. Monolayers of mesenchyme cells were prepared on tissue-culture wells. The mesenchyme cells were trapped on the surface by a thin overlay of agarose. Primary mammary epithelial cells were cultured atop this barrier layer, either as organoids in collagen gels for assessment of anchorage-dependent growth, or as single-cell dispersions in soft agarose for assessment of anchorage-independent growth. Our procedures for assay of anchorage-independent growth allow us for the first time to detect and measure this transformation-defining characteristic in non-immortalized mammary epithelial cells in primary culture. Fetal mammary fat pad precursor tissue and fetal salivary mesenchyme both stimulated anchorage dependent growth of mammary epithelium, with cell number increasing as much as fifteenfold during a 6-day culture period. These same fetal tissues also stimulated anchorage-independent growth of the mammary epithelial cells, with colony-forming efficiencies of up to 40% in co-cultures with salivary mesenchyme. No colonies formed in the absence of mesenchyme. Cells of colonies contained keratin, which indicates that the colonies grew from epithelial cells and not from a contaminant of another cell type. When co-cultured epithelial cells were subsequently re-cultured in the absence of mesenchyme, they lost their ability to grow independent of anchorage. No colonies grew in co-cultures with fetal cells from heart, kidney, or lung, which is consistent with the lack of stimulation by these tissues in the mammary gland in vivo. A tumor promoter, 12-O tetradecanoylphorbol acetate (TPA), also caused anchorage-independent growth of the dispersed mammary epithelial cells. Culture medium conditioned by primary or early-passage salivary mesenchyme cells was capable of stimulating growth under both anchorage-dependent and anchorage-independent conditions, confirming that these effects are mediated by a paracrine factor. The results indicate that stimulatory fetal mesenchymes produce soluble molecules that act analogously to transforming growth factors. PMID- 1429858 TI - Ligand-induced protein tyrosine kinase activity in living cells coexpressing intact EGF receptors and receptors with an extensive cytosolic deletion. AB - A population of stable NIH 3T3 transfectants with two molecular weight classes of membrane-bound EGF receptors encoded by a human EGF receptor cDNA has been identified and characterized. In addition to intact EGF receptors, these cells also express a molecule with an extensive cytosolic deletion. This deletion includes the ligand-activated intrinsic protein tyrosine kinase catalytic domain. Treatment with EGF caused dimerization of intact and truncated receptors, allowing us to assess protein tyrosine kinase activity in the heterodimer isolated from living cells. In contrast to homodimeric complexes with intact EGF receptor only, heterodimers were deficient in protein tyrosine kinase activity. Moreover, physical association between intact and truncated molecules suppressed receptor auto-phosphorylation by EGF receptor protein tyrosine kinase activated by antibody binding in vitro. Evidence presented here supports the idea that protein tyrosine kinase activation is facilitated by interaction between adjacent receptor molecules with intact catalytic domains. Furthermore, molecules with cytoplasmic deletions that are physically associated with kinase-active EGF receptors appear to behave as dominant negative mutations. The HerC cl cells used in this study were selected with methotrexate to amplify the EGF receptor cDNA, and in that sense may resemble certain tumor-derived cells characterized by overexpressed and rearranged EGF receptor genes. PMID- 1429859 TI - Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration. AB - Cell migration is an important process in such phenomena as growth, development, and wound healing. The control of cell migration is orchestrated in part by cell surface adhesion molecules. These molecules fall into two major categories: those that bind to extracellular matrix and those that bind to adjacent cells. Here, we report on the role of a cell-cell adhesion molecule, platelet-endothelial cell adhesion molecule-1, (PECAM-1), a member of the lg superfamily, in the modulation of cell migration and cell-cell adhesion. PECAM-1 is a 120-130 kDa integral membrane protein that resides on endothelial cells and localizes at sites of cell cell contact. Since endothelial cells express PECAM-1 constitutively, we studied the effects of PECAM-1 on cell-cell adhesion and migration in a null-cell population. Specifically, we transfected NIH/3T3 cells with the full length PECAM 1 molecule (two independent clones). Transfected cells containing only the neomycin resistance gene, cells expressing a construct coding for the extracellular domain of the molecule, and cells expressing the neu oncogene were used as controls. The PECAM-1 transfectants appeared smaller and more polygonal and tended to grow in clusters. Indirect immunofluorescence of PECAM-1 transfectants showed peripheral staining at sites of cell-cell contact, while the extracellular domain transfectants and the control cells did not. In two quantitative migration assays, the full-length PECAM-1 transfectants migrated more slowly than control cells. Thus, PECAM-1 transfected into a null cell appears to localize to sites of cell-cell contact, promote cell-cell adhesion, and diminish the rate of migration. These findings suggest a role for this cell cell adhesion molecule in the process of endothelial cell migration. PMID- 1429860 TI - The prospects for domesticating milk protein genes. AB - It is possible to convert milk glands of transgenic animals into bioreactors producing heterologous proteins such as scarce human pharmaceuticals. To predictably and successfully engineer the milk gland, we will need a thorough understanding of its physiology. Expression studies in transgenic animals have located mammary specific and hormone inducible transcription elements in the promoter/upstream regions of milk protein genes, and transfection studies in cell lines or primary cells have identified constitutive and hormone inducible elements. Most importantly, it appears that in addition to individual promoter based transcription elements structural features of milk protein chromosomal loci may contribute to the tight developmental and hormonal regulation. I will discuss milk protein gene regulation with emphasis on regulatory differences between genes and species, and the possibility that transcription elements function only properly within genetically defined chromatin domains. Novel strategies to build mammary expression vectors and to test their functionality without pursuing the standard transgenic route will be presented. Finally, I will discuss homologous recombination with the goal to target milk protein genes. Only through the domestication of milk protein genes will we be able to use their full potential in the mammary bioreactor. PMID- 1429861 TI - Isolation of recombinant proteins from milk. AB - Milk is a complex bio-colloid which presents some unique problems for the protein isolation chemist, but the majority of the processing criteria for purifying recombinant proteins are the same as with any complex biological mixture. The casein micelles and fat globules behave as separate phases; they prevent filtration of the milk and interfere with the usual separation methods. The usual first step is to centrifuge the milk to remove the fat and precipitate the casein micelles with low pH or precipitating agents. Some recombinant proteins may associate to some degree with the micelles which may necessitate solubilizing them with chelating agents. If the majority of the product protein associates with either the fat or micelles, this can be used to advantage. Once the casein micelles have been removed or disrupted, the clarified milk can be processed by the usual separation methods. There also are proteases in milk which can degrade recombinant proteins. The greatest advantage of producing recombinant proteins in milk is the high concentration which can be obtained. The high levels of product protein can alleviate many problems associated with the application of classical purification strategies to transgenic milk proteins. PMID- 1429862 TI - The phosphatidylinositol transfer protein in 3T3 mouse fibroblast cells is associated with the Golgi system. AB - By use of indirect immunofluorescence it was shown that the phosphatidylinositol transfer protein (PI-TP) in 3T3 mouse fibroblast cells is associated with the Golgi system. This was concluded from double-labeling experiments with TRITC labeled Ricin which binds to sugar residues that are specifically processed in the Golgi system. Independent evidence for this association was provided by the fact that dissociation of the Golgi system by brefeldin A was reflected in an extensive redistribution of PI-TP labeling. In addition, PI-TP is localized in the cytoplasm and in the nucleus. In exponentially growing cells an enhanced labeling of PI-TP was observed in the cytosol and in the cytosol and in the Golgi system in comparison with quiescent cells. By Western blot analysis and by transfer activity assays, it was confirmed that the concentration of PI-TP was increased in exponentially growing cells. These results strongly suggest that PI TP fulfills a role in the functioning of the Golgi complex. PMID- 1429863 TI - Interaction of multiple factors with a GC-rich element within the mitogen responsive region of the human transferrin receptor gene. AB - Nuclear factors from HeLa cells were isolated by elution of DNA-cellulose bound proteins with a double stranded synthetic oligonucleotide corresponding to the region from -34 to -79 of the human transferrin receptor (TR) gene promoter. The eluted proteins were further purified and separated from the oligonucleotide by ion exchange chromatography. Proteins within the resulting fraction bound with specificity to the TR promoter. Retardation gel analysis and competition with specific double-stranded oligonucleotides show that multiple factors present in this fraction compete for binding within the same region of the TR promoter. Footprinting experiments demonstrate that these factors contact a GC-rich element that is within the region that is required for enhanced expression of the gene in proliferating cells. One of the factors protects an extended DNA sequence but still contacts the GC-rich element. PMID- 1429864 TI - Nuclear-cytoskeletal interactions: evidence for physical connections between the nucleus and cell periphery and their alteration by transformation. AB - The overall coordination of cell structure and function that results in gene expression requires a spatial and temporal precision that would be unobtainable in the absence of structural order within the cell. Cells contain extensive and elaborate three-dimensional skeletal networks that form integral structural components of the plasma membrane, cytoplasm, and nucleus. These skeletal networks form a dynamic tissue matrix are composed of the nuclear matrix, cytoskeleton, and extracellular matrix. The tissue matrix is an interactive network which undergoes dynamic changes as cells move and change shape. Pathologists have long recognized cancer in pathologic specimens based on the altered morphology of tumor cells compared to their normal counterparts. The structural order of cells appears to be altered in transformed cells. This structural order is reflected in the altered morphology and motility observed in transformed cells compared to their normal counterparts, however, it is unclear whether the structural changes observed in cancer cells have any functional significance. We report here on the nature of the physical connections between the nucleus and cell periphery in nontransformed cells and demonstrate that the nucleus is dynamically coupled to the cell periphery via actin microfilaments. We also demonstrate that the dynamic coupling of the nucleus to the cell periphery via actin microfilaments is altered in Kirsten-ras transformed rat kidney epithelial cells. This loss of structure-function relationship may be an important factor in the process of cell transformation. PMID- 1429865 TI - Altered DNA/protein complexes specific for the beta-interferon regulatory region observed in murine embryonal carcinoma F9 cells. AB - Murine embryonal carcinoma (EC) F9 cells do not produce interferon (IFN) at the protein or RNA level in response to inducing agents, while retinoic acid differentiated F9 cells do produce IFN. A probe was constructed spanning positions -104 to -39 of the human beta-IFN upstream regulatory region to examine this developmental control at the level of a transcriptional regulatory mechanism. Gel mobility shift analyses were used to examine this molecular mechanism to determine whether the differential expression of positive or negative trans-acting factors may act to control beta-IFN expression in undifferentiated EC cells. These analyses showed that while nuclear extracts from poly-I,C induced L929 cells, in the IFN producing cell line, showed two shifted bands, nuclear extracts from both induced and uninduced F9 cells showed only one shifted band using the -104/-39 probe. While this single shifted band co-migrated with the faster migrating species of L929 cell extracts, competition analysis revealed differences between the two complexes. An oligonucleotide representing the positive regulatory domain PRDII competed efficiently for the probe when induced F9 cell extracts were examined, but failed to compete when induced L929 cell extracts were examined. In contrast, an oligonucleotide representing the positive regulatory domain PRDI competed very well when induced L929 cell extracts were examined but had only a minimal effect when induced F9 cell extracts were examined. These data suggest the involvement of developmentally regulated transcriptional factor(s) which have yet to be characterized. PMID- 1429866 TI - TPA has no influence on the expression of myosin heavy chain isoforms in cultured adult cardiac muscle cells. AB - The effect of a tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), on the expression of myosin heavy chain isoforms in cultured rat cardiac ventricular muscle cells was studied. The previous preliminary report [Claycomb WC (1988): "Biology of Isolated Adult Cardiac Myocytes." In Clark WA, Decker RS, Borg TK (eds): New York: Elsevier, pp 284-287] indicated that TPA turns off the expression of myosin heavy chain genes in cultured adult cardiac myocytes. Electrophoretic and immunocytochemical analyses were carried out in the present studies. The myosin heavy chain isoform profiles of cardiac myocytes exposed to TPA at concentrations of 50-250 ng/ml culture medium for varying periods were similar to those of controls that were grown in the absence of TPA, showing predominant isoform V1. Immunofluorescence microscopy with monoclonal antibodies to cardiac ventricular isomyosin revealed the structural organization of myosin in TPA-treated cells. The organization of myosin was variable among different myocytes and within a single myocyte. Immunofluorescence microscopy was extended to the examination of the organization of alpha-actinin which did not differ from that of myosin in some myocytes. In contrast to the previous report [Claycomb, 1988], this study has demonstrated that TPA has no influence on the expression of myosin heavy chain isoforms in cultured adult ventricular cardiac muscle cells. PMID- 1429867 TI - Alpha-1 antitrypsin response of stimulated alveolar macrophages. AB - Alpha-1 antitrypsin messenger RNA (A1AT mRNA) was determined in alveolar macrophages and in peripheral blood monocytes of healthy individuals using a sensitive RNase protection assay. Determinations were made of bacterial lipopolysaccharide (LPS) stimulated and unstimulated cells. We found that the amount of A1AT mRNA increased 7.3 and 14 times after 4 h of incubation with LPS for monocytes and macrophages, respectively (relative to total RNA). The increase was 12.3 and 14.8 times, respectively, when expressed as increase per cell. In both cell types there was wide interindividual variation in LPS response: 2-36 and 5-12 times for monocytes and macrophages, respectively. The possible significance of A1AT production of monocytes and macrophages may be the local control of granulocytic proteases such as elastase and cathepsin G. PMID- 1429868 TI - Bistratene A: a novel compound causing changes in protein phosphorylation patterns in human leukemia cells. AB - Bistratene A, a polyether toxin isolated from the colonial ascidian Lissoclinum bistratum, causes incomplete differentiation of human leukemia (HL-60) cells apparently through a mechanism not involving protein kinase C. In view of the importance of phosphorylation/dephosphorylation in cellular growth and differentiation we have investigated protein phosphorylation in these cells following exposure to bistratene A, using two-dimensional polyacrylamide gel electrophoresis. Marked increases in the phosphorylation of a protein of 20 kDa, pl 6.7, and a basic protein of 25 kDa were observed after incubation with bistratene A. A comparison was made with cells treated with 12-O tetradecanoylphorbol 13-acetate and bryostatin 5. While changes in phosphorylation patterns were observed with these two compounds, the 20 kDa and 25 kDa proteins did not undergo phosphorylation changes. The 20 kDa protein was induced rapidly by very low concentrations of bistratene A reaching near maximal levels with 10 nM at 15 min exposure. This protein was found to be localised to the cytoplasm. Phosphoaminoacid analysis demonstrated that the majority of 32P was present in serine and tyrosine residues. The increased phosphorylation of the 20 kDa protein appeared to be due to hyperphosphorylation of existing protein although there was some increase in the amount of the protein. These results suggest that bistratene A will be a useful tool with which to investigate cellular differentiation mechanisms. PMID- 1429869 TI - Effect of monensin on the sulfation of heparan sulfate proteoglycan from endothelial cells. AB - Monensin is a monovalent metal ionophore that affects the intracellular translocation of secretory proteins at the level of trans-Golgi cisternae. Exposure of endothelial cells to monensin results in the synthesis of heparan sulfate and chondroitin sulfate with a lower degree of sulfation. The inhibition is dose dependent and affects the ratio [35S]-sulfate/[3H]-hexosamine of heparan sulfate from both cells and medium, with no changes in their molecular weight. By the use of several degradative enzymes (heparitinases, glycuronidase, and sulfatases) the fine structure of the heparan sulfate synthesized by control and monensin-treated cells was investigated. The results have shown that among the six heparan sulfate disaccharides there is a specific decrease of the ones bearing a sulfate ester at the 6-position of the glucosamine moiety. All other biosynthetic steps were not affected by monensin. The results are indicative that monensin affects the hexosamine C-6 sulfation, and that this sterification is the last step of the heparan sulfate biosynthesis and should occur at the trans-Golgi compartment. PMID- 1429870 TI - Modification of blood group A antigen expression in a pancreatic cancer cell line (PC-1) by inhibitors of N-glycan processing. AB - Pancreatic adenocarcinomas induced in Syrian hamsters by treatment with N nitrosobis(2-oxopropyl) amine express blood group A antigen, which is absent in normal pancreatic cells. On membrane glycoproteins purified from tumors, blood group A antigen has been found to be expressed on multiantennary Asn-linked complex glycans. In this study, we investigated the effect of inhibitors of Asn glycan processing on blood group A antigen bearing glycan structures in a cell line (PC-1) established from a primary induced pancreatic cancer. Expression of blood group A antigen on cells and in membrane preparations was blocked by treatment with 1-deoxymannojirimycin, an inhibitor of mannosidase I, but was retained after treatment with swainsonine, an inhibitor of mannosidase II. However, swainsonine treatment altered the glycan structure associated with blood group A antigen from an endoglycosidase H resistant type to a sensitive type, indicating that the blood group A structure might shift from a complex type to a hybrid type glycan by this treatment. These results demonstrate that Asn-linked glycans carry the major blood group A antigens in PC-1 cells. PMID- 1429871 TI - Collagen increases the synthesis of membrane-associated proteoglycans produced by Sertoli cells. AB - Sertoli cells in culture produce two isoforms of proteoglycans which are found in the culture medium and associated with the cell membrane. The amount of both types of proteoglycans increased when Sertoli cells were plated on type I collagen-coated dishes as compared to uncoated dishes. The effect is due to an increase in the synthesis of proteoglycans rather than a diminished rate of degradation of these molecules. The collagen substrate also affects the distribution of these macromolecules; an increase in the amount of membrane associated proteoglycans occurs at the expense of the proteoglycans released to the culture medium. PMID- 1429872 TI - Glucocorticoid and retinoid regulation of alpha-2 type I procollagen promoter activity. AB - Glucocorticoids decrease type I procollagen synthesis by decreasing the steady state levels of procollagen mRNAs and mRNA synthesis. The present studies were undertaken to determine the functional sequences of the pro alpha 2(I) collagen gene required for the glucocorticoid-mediated decrease of type I procollagen mRNA synthesis. Embryonic mouse fibroblasts were stably transfected with the pR40 DNA CAT construct containing the 5' flanking region fragment from -2048 to +54 and the intronic fragment from +418 to +1524 of the mouse alpha 2(I) collagen gene. Dexamethasone treatment of these pR40 transfected fibroblasts resulted in a significant decrease in CAT activity which agrees with the glucocorticoid mediated decrease of the steady state levels of type I procollagen mRNAs. To determine the possible role of the first intron fragment in the dexamethasone mediated decrease of CAT activity, pR36, a CAT plasmid containing the first intron fragment and the SV40 early promoter, was transfected into mouse fibroblasts and treated with dexamethasone. No significant decrease in CAT activity was observed. The dexamethasone-mediated response was then localized within the 5' flanking region by preparing a series of constructs containing internal deletions and transfecting these plasmids into mouse fibroblasts. The regions -2048 to -981 and -506 to -351 were required for the dexamethasone response of gene activity. However, the DNA stretch from -981 to -506 was not. Analysis of the DNA sequences of these regions revealed a single GRE at -1023 to 1018 and a modified doublet at -873 to -856.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429873 TI - Nucleoprotein complexes released from lymphoma nuclei that contain the abl oncogene and RNA and DNA polymerase and RNA primase activities. AB - We report on the discovery and isolation of DNA- and RNA-containing macromolecular nuclear complexes whose purified major DNA possessed electrophoretic mobilities of approximately 90 and approximately 25 kbp. The deoxyribonucleoprotein-ribonucleoprotein complexes contain RNA and DNA polymerase and primase activities and were isolated from nuclei of murine RAW117 large-cell lymphoma cells by restriction digestion with Msp-I, gentle extraction with solutions containing MgCl2, but without chelating agents, and low ionic strength gel electrophoresis. Two-dimensional (isoelectric focusing/M(r)) gel electrophoresis and silver staining of the proteins of the complexes after treatment with DNase I indicated the presence of approximately 30 protein components. In vitro DNA and RNA polymerase/primase assays showed that the DNP/RNP complexes had very high enzyme specific activities. Using the DNP/RNP complexes a discrete DNA polymerase alpha product of approximately 85 kbp was synthesized that was not synthesized in the presence of the DNA polymerase alpha inhibitor aphidicolin. RNA polymerase assays in the presence of excess alpha amanitin indicated that the complexes possessed significant RNA polymerase I activity. Preparing the complexes at various times after the release of cells from a double thymidine block showed the complexes as well as the complex associated enzyme activities to be cell-cycle dependent. The DNA and RNA polymerase-related activities were highest in late S phase, 7 and 9 h, respectively, after release from the double thymidine block. The complexes synthesized a specific in vitro DNA polymerase product using endogenous substrate and nucleotide precursors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429874 TI - Leukoregulin, a T-cell derived cytokine, upregulates stromelysin-1 gene expression in human dermal fibroblasts: evidence for the role of AP-1 in transcriptional activation. AB - Leukoregulin (LR), a product of activated T-cells, has been recently shown to modulate the metabolism of extracellular matrix components in human skin fibroblast cultures (Mauviel et al., J Cell Biol 113:1455-1462, 1991). In this study we focused our attention on the effects of LR on the expression of stromelysin-1 gene. This matrix metalloprotease has a broad spectrum of degradative activity and it is also required for maximal activation of interstitial collagenase. Incubation of skin fibroblast cultures with LR resulted in a dose- and time-dependent elevation of stromelysin-1 mRNA levels, the maximum enhancement being up to approximately sevenfold. This effect was abolished by cycloheximide, suggesting a requirement for ongoing protein synthesis. Transient cell transfections with a promoter/reporter gene construct containing 1.3 kb of 5' flanking DNA of the human stromelysin-1 gene linked to the chloramphenicol acetyl transferase (CAT) gene, indicated enhancement of promoter activity by LR. This enhancement was abolished by a single base substitution in the AP-1 binding site of the promoter. Furthermore, gel mobility shift assays demonstrated enhanced AP-1 binding activity in nuclear extracts from cells incubated with LR. However, LR did not alter the activity of a construct containing three AP-1 sequences in front of the thymidine kinase promoter linked to the CAT gene. These results collectively suggest that activation of stromelysin-1 gene expression by LR is mediated by AP-1 regulatory elements which are necessary, but not sufficient, for gene response. PMID- 1429875 TI - Differential regulation of H4 histone gene expression in 3T3-L1 pre-adipocytes during arrest of proliferation following contact inhibition or differentiation and its modulation by TGF beta 1. AB - The aim of this study was to address whether there is a fundamental difference in regulation of histone gene expression in cells that have become quiescent but retain the ability to proliferate, compared with those cells that have differentiated. We compared multiple levels of regulation of histone gene expression during 3T3-L1 pre-adipocyte differentiation. Confluent cells induced to differentiate by treatment with insulin, dexamethasone, and isobutylmethylxanthine initially exhibited an increased proliferative response compared with cells given serum alone. This initial differentiation response was associated with a twofold increase in both histone gene transcription and cellular histone mRNA levels, as well as with enhanced sequence-specific binding of nuclear factors to the proximal cell-cycle-regulatory element of the H4 histone promoter. Transforming growth factor beta 1, an inhibitor of 3T3-L1 differentiation, increased both the percentage of proliferating cells and the cellular levels of histone mRNA when given in addition to serum stimulation, but no enhancement of these parameters was observed upon addition of TGF beta 1 to the differentiation treatment. Interestingly, although TGF beta 1 enhanced binding of nuclear factors to the proximal cell cycle regulatory element of the histone promoter, these protein/DNA interactions were not associated with an increase in histone transcription. Our results are consistent with the down regulation of histone gene expression at confluency being controlled primarily at the post-transcriptional level, in contrast to an increased involvement of transcriptional down-regulation at the onset of differentiation. PMID- 1429877 TI - Evidence for the presence of complex high-molecular mass N-linked oligosaccharides in intranuclear glycoproteins from HeLa cells. AB - Nonhistone proteins were extracted in 0.4 M NaCl from membrane-depleted nuclei of HeLa cells grown in the presence or the absence of [5,6-3H]fucose. Control experiments strongly suggest that most extracted proteins were indeed nuclear components. Several proteins, present in the 0.4 M NaCl nuclear extract, with M(r) ranging from 35,000 to 115,000 were identified on Western blots as fucosylated glycoproteins owing to their binding to the fucose-specific lectin, Ulex europeus agglutinin I. Results of experiments involving mild alkaline treatment and peptide N-glycosidase F digestion showed that the carbohydrate moieties of these fucosylated nuclear glycoproteins were N-linked to the polypeptide backbone. Analysis of the N-glycans revealed the presence of two populations of sialylated oligosaccharides on the basis of their relative molecular masses. The sensitivity of the high-M(r) oligosaccharides to endo-beta galactosidase and their incorporation of [3H]glucosamine suggest that they could contain repeating N-acetyllactosamine units. [3H]Fucose incorporated into nuclei was confined to the nucleoli, as judged by autoradiography of sections cut through cells grown in the presence of [3H]fucose. Electron microscopy autoradiography showed that the fibrillar centers were never labeled, while silver grains were observed on the dense and the granular components of nucleoli. Taking into account of these data most nuclear fucosylated glycoproteins extracted in 0.4 M NaCl might be nucleolar ribonucleoproteins. PMID- 1429876 TI - A cell attachment peptide from human C-reactive protein. AB - The serum acute phase reactant, C-reactive protein (CRP), is selectively deposited at sites of tissue damage and degraded by neutrophils into biologically active peptides. A synthetic peptide corresponding to residues 27-38 present in each of the five identical subunits of CRP mediated cell attachment activity in vitro. Although the CRP-derived peptide contains a Tuftsin (TKPR)-like sequence at its amino-terminus, the Tuftsin tetrapeptide itself, as well as several synthetic peptides of CRP, failed to inhibit the cell-attachment activity to the CRP-derived peptide. Peptides containing the sequences responsible for the cell attachment activity of the extracellular matrix proteins, fibronectin (Fn) and laminin, failed to inhibit the CRP-derived peptide cell attachment activity. However, the addition of the RGDS and RGDSPASSLP cell-binding peptides of Fn to cells enhanced attachment to the active peptide from CRP. In the converse experiment, the cell-binding peptide of CRP did not influence cell attachment to Fn or laminin. A peptide corresponding to the same stretch of amino acid residues within the homologous Pentraxin, serum amyloid P-component (SAP), displayed nearly identical cell-attachment activity. Several monoclonal antibodies (mAb) specific for the CRP-derived cell-binding peptide neutralized its cell-attachment activity. These mAbs reacted with intact CRP and neutralized the cell-binding activity of CRP itself. The findings suggest that a peptide with cell-binding activity could be generated from the breakdown of CRP and then contribute directly to cellular events leading to tissue repair. PMID- 1429878 TI - Homeotic protein binding sites, origins of replication, and nuclear matrix anchorage sites share the ATTA and ATTTA motifs. AB - Nuclear matrix organizes the mammalian chromatin into loops. This is achieved by binding of nuclear matrix proteins to characteristic DNA landmarks in introns as well as proximal and distal sites flanking the 5' and 3' ends of genes. Matrix anchorage sites (MARs), origins of replication (ORIs), and homeotic protein binding sites share common DNA sequence motifs. In particular, the ATTA and ATTTA motifs, which constitute the core elements recognized by the homeobox domain from species as divergent as flies and humans, are frequently occurring in the matrix attachment sites of several genes. The human apolipoprotein B 3' MAR and a stretch of the Chinese hamster DHFR gene intron and human HPRT gene intron shown to anchor these genes to the nuclear matrix are mosaics of ATTA and ATTTA motifs. Several origins of replication also share these elements. This observation suggests that homeotic proteins which control the expression level of many genes and pattern formation during development are components of the nuclear matrix. Thus, the nuclear matrix, known as the site of DNA replication, might sculpture the crossroads of the differential activation of origins during development and S phase and the control of gene expression and pattern formation in embryogenesis. PMID- 1429879 TI - The rapid nongenomic actions of 1 alpha,25-dihydroxyvitamin D3 modulate the hormone-induced increments in osteocalcin gene transcription in osteoblast-like cells. AB - We have previously shown that one of the rapid nongenomic actions of 1 alpha,25 dihydroxyvitamin D3 (1 alpha,25-(OH)2D3), the increase in intracellular calcium (Ca2+), accompanies the increased osteocalcin (OC) mRNA steady-state levels in rat osteosarcoma cells. To determine the functional significance of the nongenomic actions, we have measured changes in intracellular Ca2+ as an indicator of the rapid effects and have assessed the effect of inhibition of the rapid increase in cellular Ca2+ by the inactive epimer, 1 beta, 25 dihydroxyvitamin D3 (1 beta,25-(OH)2D3), on OC mRNA steady-state levels and transcription. 1 beta,25-dihydroxyvitamin D3 inhibited 1 alpha,25-(OH)2D3 induced increases in intracellular Ca2+ and OC mRNA transcription at 1 hr and OC mRNA steady state levels at 3 hr. 1 beta,25-Dihydroxyvitamin D3 did not alter the binding of the vitamin D receptor complex to the vitamin D responsive element of the OC gene. The results demonstrate the functional importance of the rapid, nongenomic actions of 1 alpha,25-(OH)2D3 in the genomic activation of the OC gene by the hormone in rat osteoblast-like cells, perhaps by modifying subtle structural and/or functional properties of the vitamin D-receptor DNA complex or by affecting other protein DNA interactions that support OC gene transcription. PMID- 1429880 TI - The mammalian iris-ciliary complex affects organization and synthesis of cytoskeletal proteins of organ and tissue cultured lens epithelial cells. AB - A water soluble growth inhibitor was isolated from the mammalian ocular iris ciliary complex. The molecular weight of this protein is 10 kD or lower as determined by ultrafiltration fractionation. The iris-ciliary (IC) complex water soluble protein(s) significantly inhibits synthesis of lower molecular weight proteins of the epithelial cells of the organ cultured mammalian ocular lens. It was also found that this inhibitory effect of IC is mediated via the structural organization of the lens. Monolayer cultures of the lens epithelial cells exposed to IC did not manifest any inhibition of their protein synthesis. Moreover, these tissue cultured lens epithelial (TCLE) cells showed a significant increase in their protein synthetic activities in response to the presence of IC factors in the culture medium. It is postulated that the IC activity is modulated via either the lens capsule, an extracellular matrix, or due to the specific organization of the intact lens. The specific effects of IC on the cytoskeletal organization and synthesis in the organ cultured lens epithelial (OCLE) and TCLE cells were also examined. Both groups, treated with IC factors, manifested significant alterations in their protein synthetic activities and cytoskeletal architecture. The 3H-leucine incorporation experiments showed that alpha-actin and alpha tubulin synthesis is partially inhibited by IC factors in OCLE cells but vimentin synthesis is not, whereas in TCLE cells all of them showed increased synthesis in response to IC factors. Turnover rates of these proteins in both OCLE and TCLE cells were also computed. The immunofluorescence and microscopic evaluation of OCLE and TCLE cells exposed to IC factors illustrated significant alteration in the cytoarchitecture of the filaments. We demonstrate that an inhibitor(s) molecule of 10 kD or lower size isolated from IC inhibited protein synthesis of OCLE cells and stimulated protein synthesis in TCLE cells. The IC factor also affects the synthesis and organization of cytoskeletal filaments of both the OCLE and TCLE cells. PMID- 1429881 TI - Replacement of lysine-181 by aspartic acid in the third transmembrane region of endothelin type B receptor reduces its affinity to endothelin peptides and sarafotoxin 6c without affecting G protein coupling. AB - A conserved aspartic acid residue in the third transmembrane region of many of the G protein-coupled receptors has been shown to play a role in ligand binding. In the case of endothelin receptors, however, a lysine residue replaces this conserved aspartic acid residue. To access the importance of this residue in ligand binding, we have replaced it with an aspartic acid in the rat endothelin type B (ETb) receptor by PCR mediated mutagenesis. The binding characteristics and functional properties of both the wild type and mutant receptors were determined in COS-7 cells transiently expressing the cloned receptor cDNAs. Using 125I-ET-1 as the radioactive peptide ligand in displacement binding studies, the wild type receptor displayed a typical non-isopeptide-selective binding profile with similar IC50 values (0.2-0.6 nM) for all three endothelin peptides (ET-1, ET 2, and ET-3) and sarafotoxin 6c (SRTX 6c). Interestingly, the mutant receptor showed an increase in IC50 values for ET-1 (5 nM), ET-2 (27 nM), and ET-3 (127 nM) but displayed a much larger increase in IC50 value for SRTX 6c (> 10 uM). The lysine mutant receptor still elicited full inositol phosphate (IP) turnover responses in the presence of saturating concentrations of endothelins (10 nM of ET-1, 100 nM of ET-2, or 1 uM of ET-3), indicating that the mutation (K181D) did not affect the coupling of mutant receptor to the appropriate G protein. These results demonstrate that lysine-181 on the receptor is important for binding ET peptides; however, it is required for binding the ETb selective agonist-SRTX 6c. PMID- 1429882 TI - Stable expression of a cDNA encoding a human beta 1 --> 3galactosyltransferase responsible for lacto-series type 1 core chain synthesis in non-expressing cells: variation in the nature of cell surface antigens expressed. AB - Transient expression of a human colonic adenocarcinoma Colo 205 cell derived cDNA in cell lines which ordinarily express only neolacto-series glycolipids has resulted in the expression of a beta 1 --> 3galactosyltransferase gene responsible for synthesis of glycolipids based upon the lacto-series type 1 core chain. Calcium phosphate transfected cells were panned on anti-IgM coated plates after initial treatment with a combination of monoclonal antibodies specific for type 1 chain terminal structures (TE-3) and a very broadly specific antibody reactive with multiple type 1 chain derivatives (TE-2). Adherent cells after panning were capable of efficiently transferring Gal in beta 1 --> 3-linkage to the acceptor glycolipid Lc3. Using these reagents, clones of stably transfected human colonic adenocarcinoma HCT-15 cells were produced and isolated. Parental HCT-15 cells do not express type 1 chain based antigens. The nature of the type 1 chain based antigens produced in each of these clones was analyzed by solid phase antibody binding assays. Three types of behavior were observed. Formation of type 1 terminal structures that were either exclusively sialylated or fucosylated, or a mixture of sialylated and fucosylated determinants occurred. In contrast, no difference in type 2 antigen expression between any clone and the parental cells was observed. These data suggest that coordination of subsequent reactions capable of modifying type 1 chain structures is not the same in all clones. The relationship of these results to aspects of cellular regulation of carbohydrate biosynthesis is discussed. PMID- 1429883 TI - Comparison of the mouse L32 ribosomal protein promoter elements in mouse myoblasts, fibers, and L cells. AB - The sequences required for the maximal expression of the mouse L32 ribosomal protein gene and the binding of nuclear factors to L32 promoter elements were analyzed in mouse myoblasts, fibers, and L cells. Various L32 r-protein promoter sequences were linked to the chloramphenicol acetyltransferase gene (CAT), and the expression of the chimeric genes was measured transiently or after their incorporation into the genome. The sequence requirements for maximal expression of the L32 gene are very similar among the various cells and include the previously identified L32 core promoter from approximately -150 to +75. Only the promoter regions between -45 and +11 displays significant cell type specific differences. Relative to the maximal activity in each cell type, the expression of the L32-CAT gene containing the -45 to +11 region is greater in L cells than in myoblasts or fibers. This difference is correlated with the increased activity of an L cell nuclear factor(s) that binds to this fragment. In addition, our results show that deletion of sequences between -981 and -141 causes a 50-70% reduction of the expression of the L32-CAT gene in myoblasts, fibers and L cells. The transcription of all the L32-CAT genes examined decrease after myoblasts differentiate into fibers in a manner similar to the endogenous L32 gene, but we were unable to distinguish between sequences involved in controlling the expression of the L32 gene during myoblast differentiation and those sequences required for maximal promoter activity. However, gel mobility shift assays showed differences in the binding of myoblast and fiber factors to the four promoter fragments examined. The possible role of these factor binding differences in controlling L32 transcription is discussed. PMID- 1429884 TI - Poly ADP-ribosylation: a histone shuttle mechanism in DNA excision repair. AB - In DNA excision repair of mammalian cells, the processing of ADP-ribose by the poly ADP-ribosylation system of chromatin is stimulated several thousand-fold. Most of this turnover is associated with the automodification reaction of the nuclear enzyme poly(ADP-ribose) polymerase and the degradation of polymerase bound polymers by the enzyme poly(ADP-ribose) glycohydrolase. The automodification cycle catalyzes a temporary dissociation from and reassociation of histones with DNA. It is proposed that this mechanism, termed "histone shuttle", may guide specific proteins to sites of repair. In addition, histone shuttling driven by the poly ADP-ribosylation system seems to be involved in nucleosomal unfolding of chromatin in DNA excision repair. PMID- 1429885 TI - Synchronization of hair cell regeneration in the chick cochlea following noise damage. AB - Pure-tone overstimulation for prolonged time leads to hair cell death in frequency-specific regions of the cochlear epithelium. Unlike mammals, birds replace missing hair cells by stimulating mitosis in an uncharacterized precursor cell. Regenerated hair cells, initially identifiable by their immature stereocilia and small surface areas, differentiate into mature cells in a manner which parallels embryonic development. In the current study, we examined whether hair cell regeneration is initiated during noise exposure or after the end of acoustic trauma. We exposed 7-to 15-day-old chicks to a 1500 Hz pure tone at 120 dB SPL (re 20 muPa) for 4, 12, and 24 hours and examined the recovering cochlear epithelium with scanning electron microscopy to determine when regenerated hair cells were first identifiable. The earliest evidence of new hair cells appeared roughly 96 hours after the onset of 4-, 12-, and 24-hour exposures. Our previous studies initially identified new hair cells 96 hours after the start of a 48-hour exposure. Therefore, hair cell regeneration follows a similar time course relative to the onset of noise exposure, regardless of the ultimate duration of exposure. Since we estimate that hair cells take at least 48 hours after their genesis to form immature stereocilia, the signal which induces hair cell precursors to re-enter the cell cycle and to divide probably has its initial effects very early during the exposure period. (A previous report of these data was given at the 1991 American Society for Cell Biology conference.) PMID- 1429886 TI - Evolution and the meaning of metaphase. AB - We used an evolutionary test to ask whether the congression of chromosomes to the spindle equator is important in itself or just a mitotic happenstance. If congression matters, then it might evolve if absent initially. Previous workers established that newly made trivalents, meiotic units of three chromosomes, generally do not congress to the spindle equator. Instead, these young trivalents lie close to the pole to which two of the three chromosomes are oriented. We studied ancient sex-chromosome trivalents that arose hundreds of thousands to several million years ago in several species of praying mantids and one grasshopper. All these old trivalents lie near the spindle equator at metaphase; some of them congress as precisely to the equator as the ordinary chromosomes in the same cells. We conclude that congression evolved independently two or three times in the materials studied. Therefore, the metaphase position of chromosomes midway between the poles appears to matter, but why? In the praying mantids, the evident answer is that metaphase is a quality-control checkpoint. Sometimes the three chromosomes are not associated in a trivalent but rather are present as a bivalent plus an unpaired chromosome, which lies near one pole. Earlier workers showed that such cells are blocked in metaphase and eventually degenerate; this prevents the formation of sperm with abnormal combinations of sex chromosomes. We suggest that the quality-control system would have trouble distinguishing an unpaired chromosome from an uncongressed, newly arisen trivalent, both of which would lie near a spindle pole. If so, the confused quality-control system would block anaphase imprudently, causing a loss of cells that would have produced normal sperm. Hence, we conclude that the congression of the trivalent to the equator probably evolved along with the metaphase quality-control checkpoint. The mechanism of congression in old trivalents is uncertain, but probably involves an interesting force-sensitive regulation of the motors associated with particular chromosomes. We also examined the congression of two newly made quadrivalents when they orient with three kinetochores to one pole and one to the other. As others have described, one of these quadrivalents does not congress, while the other quadrivalent comes closer than expected to the spindle equator. Such variation in the extent of congression may provide materials on which natural selection can act, leading to the evolution of congression. The trivalents of praying mantids are attractive materials for further studies of the mechanism of congression and of the idea that metaphase is a checkpoint for progression through the cell cycle. PMID- 1429887 TI - Stimulus-dependent relocation of the microtubule organizing center in human polymorphonuclear leukocytes. AB - Polymorphonuclear leukocytes (PMNs) exhibit extensive directional migration (chemotaxis) and phagocytic activities. We have developed an in vitro model to evaluate the organization of the microtubule organizing center (MTOC) in PMNs as the latter interact with various substrata, including immobilized antigen antibody complexes. PMNs were layered on poly-L-lysine substrata containing ferritin (PL+F) or ferritin-antiferritin complex (PL+F+AF) and the location of MTOCs was determined by indirect immunofluorescence of tubulin using conventional epifluorescence microscopy and confocal laser scanning microscopy. The MTOCs in the majority of the PMNs attached to PL+F occupied an apical location (81.29% +/- 3.34%), while in the majority of PMNs layered onto PL+F+AF, a basal location (79.37% +/- 5.26%) was observed. Following disruption of microtubules (MTs) by nocodazole before layering the cells on the substrata, the proportions of PMNs with apical MTOCs were 65.2% +/- 6.27% for PL+F and 47.2% +/- 4.1% for PL+F+AF substrata, while the proportions of PMNs with basal MTOCs were 26.11% +/- 8.89% for PL+F and 39.6% +/- 4.4 for PL+F+AF substrata. The results indicate that MTOCs in human PMNs in vitro (i) occupied a 'pre-defined' apical location; (ii) translocated to a 'newly defined' basal location upon stimulation with immobilized antigen-antibody complex; (iii) and depended on intact MTs for placement of MTOCs in both situations. PMID- 1429888 TI - Relocation of nucleolar proteins around chromosomes at mitosis. A study by confocal laser scanning microscopy. AB - The behaviour of nucleolar antigens known to associate with chromosomes at mitosis was investigated in mammalian cells (HeLa, HEp-2, PtK1, CHO) by immunofluorescence and confocal laser scanning microscopy. Serial optical sections through mitotic cells, from prophase to telophase, were used to generate three-dimensional images of the antigen distribution. Our results indicate that, at the onset of mitosis, these antigens leave the nucleoli in a highly ordered manner to form a network extending from the nucleoli towards the nuclear envelope. The migration begins at very early prophase, when the condensation of the chromosomes is not yet visible. After completion of the migration at late prophase, the labelling is found at the chromosome periphery. The antigens remain distributed as a sheath surrounding the chromosomes from prophase to telophase. Therefore, the proteins involved in the formation of this perichromosomal layer have different behaviour than those of the prenucleolar bodies. The antigens appear to interact strongly with chromosomes, since they are not lost during chromosome isolation in hypotonic buffer. Each chromosome is entirely covered from one telomere to the other, except in the centromeric region. Thus the relocation of these nucleolar proteins does not appear to be the result of a passive accumulation at the chromosome periphery, but seems rather to be due to an active targeting to specific sites. Consequently, these proteins may have a determining function in the progression of the cells through mitosis, possibly by participating in the protection and stabilization of the chromosomes. PMID- 1429889 TI - Microinjection of antibodies against talin inhibits the spreading and migration of fibroblasts. AB - Talin is believed to be one of the key proteins involved in linking actin filaments to extracellular matrix receptors in focal adhesions. Our strategy for studying the function of talin has been to inactivate talin in living fibroblasts in tissue culture through the microinjection of affinity-purified, polyclonal anti-talin antibodies. The effect of the injected anti-talin antibodies on cell spreading was found to depend on how recently the cells had been plated. Cells that were in the process of spreading on a fibronectin substratum, and which had newly developed focal adhesions, were induced to round up and to disassemble many of the adhesions. However, if fibroblasts were allowed to spread completely before they were microinjected with the anti-talin antibody, focal adhesions remained intact and the flat morphology of the cells was unaffected. The percentage of cells that were able to maintain a spread morphology despite the injection of anti-talin antibodies increased during the first few hours after plating on fibronectin substrata. Fibroblasts that were allowed to spread completely before microinjection with the anti-talin antibody retained both intact focal adhesions and a flat, well-spread morphology, but failed to migrate effectively. Our experiments do not directly address the role of talin in mature focal adhesions, but they indicate that talin is essential for the spreading and migration of fibroblasts on fibronectin as well as for the development and initial maintenance of focal adhesions on this substratum. PMID- 1429890 TI - Mammalian skeletal muscle C-protein: purification from bovine muscle, binding to titin and the characterization of a full-length human cDNA. AB - We report a fast method for the isolation of homogeneous C-protein from bovine skeletal muscle. In electron micrographs C-protein appears as short rods with a relatively uniform length of about 50 nm. Protein sequencing shows a single N terminal sequence. Radio-labelled C-protein strongly decorates titin II and myosin rods but not myosin heads. Binding to titin II is retained in preparations lacking titin-associated proteins. Antibodies to bovine C-protein were used to screen a lambda gt11 cDNA library constructed from fetal human skeletal muscle. Clone HC38 is 3833 bp long and encodes a protein of 1138 amino acid residues. The start of the predicted sequence fits the N-terminal sequence of the bovine protein. All partial sequences obtained from the bovine protein (348 residues) and the sequence deduced from a partial chicken cDNA (Einheber and Fischman, 1990) can be aligned along the human sequence. The sequences of human and chicken C-proteins share 50% identity and 70% similarity. Along the repeat patterns of the human protein the fibronectin (Fn)-like domains are better conserved than the immunoglobulin (Ig)-like domains. Regions of strong divergence between chicken fast C-protein and human slow C-protein may represent differences in C-protein isoforms. PMID- 1429891 TI - Formation of skeletal muscle in vivo from the mouse C2 cell line. AB - The C2 muscle cell line is myogenic in vitro and has been extensively used in studies of muscle cell differentiation. Here, we have investigated the myogenicity in vivo of C2 cells implanted into suitable sites in the mouse. Large amounts of new muscle were formed when C2 cells were implanted into sites in nude mice which were undergoing regeneration following whole muscle grafting and in scaffolding of freeze-killed muscle or vicryl suture in the anterior tibial compartment. When implanted into regenerating muscle, C2 cells fused with the host muscle to form mosaic fibres; when implanted into inert sites, they formed muscle of largely donor origin. C2-derived muscle fibres appeared to become innervated, but the progression of N-CAM (neural cell adhesion molecule) isoform changes in such regenerates indicated that they did not become fully mature. Proliferating, undifferentiated cells of C2 origin form tumours in older grafts; however, this was more pronounced in the absence of competition from host muscle cells. In the short term, C2 cells can form large amounts of muscle in vivo for biochemical analysis. In addition, C2 cells are easily manipulable in vitro; genes of interest may be transfected into them prior to implantation of the cells into skeletal muscle and the effects of these genes in vivo may thus be examined. PMID- 1429892 TI - An evaluation of cell separation techniques in a model mixed cell population. AB - Muscle precursor cells may act not only as a means of inserting normal genes into diseased muscle fibres, in order to correct or alleviate a genetically inherited myopathy, but recent demonstrations have shown they may prove an invaluable tool for the expression of, and systemic dissemination of, non-muscle gene products. If muscle precursor cells are proved to act as such widespread vectors in terms of gene therapy, then it is imperative that methods are properly elucidated to produce large populations of pure viable myogenic cells for such purposes. In the past, many methods of cell separation have been investigated but carry with them the problems of either a lack of myogenic purity of the population or poor percentage recovery of the original cell population. In the present work we have investigated two methods for segregating myogenic from non-myogenic cells and have critically reviewed the efficiency of separation of the two techniques used. To obtain a quantitative measure of separation efficiency, segregation was carried out on a 1:1 mixture of murine C2 myogenic and murine 3T3 fibroblastic cells. To distinguish between C2 and 3T3 cells, the latter were prelabelled with the fluorescent strain carboxyfluorescein diacetate succinimyl ester (CFSE). Once incorporated into the cell, CFSE remains there, thus preventing transfer of the label to C2 cells. Both methods of separation used depend on the affinity of myogenic cells for the monoclonal antibody Mab H28, which specifically binds to the mouse neuronal cell adhesion molecule N-CAM, but differ in that one method, "panning", completes segregation by adherence of N-CAM positive cells to a dish precoated with secondary IgG antibody whereas in the other separation proceeds by the use of commercially available IgG-coated magnetic beads. Results indicate magnetic bead separation to be more efficient than panning if the beads are precoated with 0.1% gelatin. PMID- 1429893 TI - Aortic endothelial cell heterogeneity in vitro. Lack of association between morphological phenotype and collagen biosynthesis. AB - Previous reports dealing with the characterisation of endothelial cells derived from the same tissue have produced apparently conflicting results in fundamental cellular attributes such as matrix biosynthesis and the ability to form sprouts in vitro. One potential explanation for this discrepancy is that endothelial cells actually comprise a heterogeneous population of cells displaying a significant degree of intra-site variation in phenotype. In order to address this question, we have characterised both cloned and uncloned lines of bovine aortic endothelial cells with respect to (a) their ability to adopt both the cobblestone and sprouting cell phenotypes and (b) matrix biosynthesis by cells displaying these two phenotypes. Data are presented indicating that all of the 18 cloned and 20 uncloned cell lines examined were capable of undergoing a reversible transition between the cobblestone and sprouting cell phenotypes in response to culture conditions. In all cases, sprouting occurred spontaneously in the presence of either serum or platelet-poor plasma and did not require the addition of exogenous factors to the medium. Twelve lines of cells were examined with respect to protein biosynthesis; these lines produced different types of collagens in differing proportions. The pattern of collagen synthesis displayed by every cell line was stable and did not vary with either passage number or batch of serum. The presence of a 3-D gel of native type I collagen increased specifically the synthesis of type IV collagen by one cell line. However, in four other cell lines, even though total synthesis was increased, the type of proteins secreted by these cells was not altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429894 TI - Changes in cell surface expression of fibronectin and fibronectin receptor during liver regeneration. AB - The surface expression of fibronectin and its major integrin receptor in liver, integrin alpha 5 beta 1, was studied during liver regeneration after partial hepatectomy. Using immunoblotting, plasma membranes isolated from livers at different regeneration stages were found to contain 6- to 8-fold elevated levels of fibronectin, alpha 5 and beta 1 at 12-24 h after the operation. Normal levels were gradually restored during the following 8-9 days. The membrane-associated fibronectin lacked the ED-A domain, suggesting that it consisted of plasma fibronectin. A prominent fibronectin fragment (180 kDa) was present at 12-24 h after surgery, possibly reflecting turnover of the pericellular matrix during cell division. Indirect immunohistochemical staining of liver sections revealed beta 1 and fibronectin mainly in the sinusoidal region of the hepatocyte plasma membrane. The distribution was not markedly altered during liver regeneration. The results suggest that the fibronectin-mediated contacts between the cells and the extracellular matrix increase during the pre-replicative and proliferative phases of liver regeneration. The significance of these results for the growth and for the structure of the liver during regeneration and development is discussed. PMID- 1429895 TI - Alteration in glycosaminoglycan metabolism and surface charge on human umbilical vein endothelial cells induced by cytokines, endotoxin and neutrophils. AB - There is increasing evidence that the glycosaminoglycan (GAG) component of the vascular endothelium is important in regulating vascular permeability, thromboresistance and cellular interactions. We have investigated the GAG metabolism of cultured human umbilical vein endothelial cells (HUVEC) in response to a range of inflammatory stimuli. Using both chemical measurement of cellular and supernatant GAGS and 35S labelling to identify newly synthesised GAGS, interleukin 1 (IL1), tumour necrosis factor (TNF) and interferon gamma (IFN gamma) were shown to influence sulphated GAG metabolism significantly. IL1 and TNF caused a marked increase in culture supernatant GAGS and a concomitant reduction in cell-associated GAGS. This was shown histochemically to be associated with a marked reduction and redistribution of endothelial surface anionic sites. The addition of neutrophils to HUVEC pretreated with Escherichia coli endotoxin, IL1 or TNF resulted in a further reduction in both cellular GAGS and surface anionic sites. These results suggest that changes in endothelial cell GAG metabolism during inflammation may contribute to the disturbance of vascular endothelial homeostasis associated with infectious and inflammatory states. PMID- 1429896 TI - Molecular characterisation of the gene for the 180 kDa subunit of the DNA polymerase-primase of Drosophila melanogaster. AB - We have cloned and sequenced the gene for the 180 kDa subunit of the a polymerase from Drosophila melanogaster. The protein shows high similarity to the 180 kDa subunits from other species. Comparative expression analysis for the transcript, protein and enzymic activity suggests that control occurs mainly at the level of transcription. In situ analyses of the RNA suggest that high levels of the transcript are synthesised in the ovaries and deposited uniformly in the egg. Immunolocalisation of the 180 kDa polypeptide in whole embryos shows that its location is mainly nuclear; however, dispersal of the protein can be seen to occur during mitotic phases of the cell cycle. PMID- 1429897 TI - Isoprenylation of rab proteins on structurally distinct cysteine motifs. AB - rab proteins are low molecular weight GTP-binding proteins highly related to Ypt1p and Sec4p, which are involved in the control of secretion in yeast Saccharomyces cerevisiae. Morphological and biochemical studies have shown that rab proteins are membrane associated and are localized to specific subcompartments along the exocytic and endocytic pathway. Membrane association requires the presence of C-terminal cysteine residues. The present report indicates that the structurally distinct cysteine motifs of rab proteins are subjected to isoprenylation both in vitro and in vivo. Studies on deletion mutants suggest that an intact C-terminal end is required for the association of rab proteins with the membrane and is necessary for the post-translational modification. Finally, we show that the isoprenoid transferase which modifies rab termini is different from the enzyme which farnesylates nuclear lamins and ras proteins in vitro. PMID- 1429898 TI - M-CSF-induced macropinocytosis increases solute endocytosis but not receptor mediated endocytosis in mouse macrophages. AB - Although coated vesicles can mediate both solute and receptor-mediated endocytosis, there are other kinds of endocytic vesicles that contribute to these processes. The relative contributions of these other organelles, particularly regarding solute influx, remains unsettled. Here we describe a physiological uncoupling of solute and receptor-mediated endocytosis that occurs during growth factor-stimulated macropinocytosis. We examined how recombinant human macrophage colony-stimulating factor (rM-CSF), which rapidly stimulates solute endocytosis in murine bone marrow-derived macrophages, affected ligand internalization via receptor-mediated endocytosis. Although rM-CSF stimulated internalization and accumulation of Lucifer Yellow (LY), a probe for solute endocytosis, it had no effect on accumulation of fluorescent acetylated low-density lipoprotein (acLDL), a ligand for the macrophage scavenger receptor, or on the endocytosis of 125I labelled diferric transferrin. Video microscopy revealed that rM-CSF immediately induced active cell ruffling and the formation of phase-bright macropinosomes. Nocodazole pretreatment of macrophages inhibited both ruffling and macropinocytosis. Macropinosomes were fluorescently labelled by incubating macrophages briefly with probes for both solute endocytosis (fluorescent dextrans) and ligand endocytosis (fluorescein-labelled transferrin or diI labelled acLDL). Macrophages incubated for one or two minutes formed macropinosomes that were labelled predominantly with the fluorescent solute probes but with little or none of the ligand probes; the latter were localized within smaller pinosomes. When cells pulsed with the fluorescent probes were washed and chased for an additional two minutes, solute and ligand probes occasionally co-localized in macropinosomes. Nocodazole inhibited macropinocytosis with little apparent effect on endocytosis via smaller vesicles. These experiments show that macropinosome formation is dependent on microtubules and also that the macropinosomes induced by rM-CSF are solute-rich and receptor poor. Macropinosomes differ from coated vesicles in these respects, and therefore provide a physiologically regulated mechanism for uncoupling solute and receptor mediated endocytosis. PMID- 1429899 TI - Endocytosis: what goes in and how? PMID- 1429900 TI - Chromosomes attain a metaphase position on half-spindles in the absence of an opposing spindle pole. AB - To examine the relative roles of chromosomes, spindle poles and microtubules in the formation of the metaphase spindle and metakinesis, I have experimentally placed an extra centrosome-free pronucleus close to a forming bipolar spindle in a living cell. The chromosomes from the extra nucleus induce the formation of an extra half-spindle from one pole of the otherwise normal bipolar spindle with chromosomes positioned at the putative metaphase plate. I conclude that chromosomes determine the location of half-spindles by sustaining a higher than normal density of microtubules. These results are surprising for two reasons: first, because previous in vivo experiments in tissue culture cells show that mono-oriented chromosomes with functional attachments to spindle microtubules do not support half-spindle formation but oscillate unstably or move to one spindle pole. Additionally, the generally accepted view is that chromosomes attain a metastable condition at the metaphase plate as a result of a balance between forces directed to opposite spindle poles. However, our observation that chromosomes on extra half-spindles attain a metastable position in the absence of an opposing spindle pole, suggests that Ostergren's model does not account for metakinesis in sea urchin embryos. PMID- 1429902 TI - Double localization of F-actin in chemoattractant-stimulated polymorphonuclear leucocytes. AB - Uniform concentrations of chemoattractants such as formylpeptides induced a morphological polarization of human polymorphonuclear leucocytes (PMNs) and a concentration of F-actin at the cell front. They also induced a transient increase in filamentous actin (F-actin) which preceded the cell shape change. We combined fluorescence microscopy and image analysis to study the localization of F-actin, as revealed by a specific probe (bodipyTM phallacidin) in suspended PMNs stimulated by chemoattractants. F-actin exhibited remarkable concentration in focal points after a 30 s exposure to 10(-8) M formylmethionyl-leucyl phenylalanine (fMet-Leu-Phe), although no shape change of PMNs was detectable. A 10-min incubation with formylpeptide (10(-6) to 10(-9) M) induced the morphological polarization of PMNs and the appearance of a principal focus of F actin in the cell head region and a secondary focus in the cell posterior end. The distribution of F-actin-associated fluorescence in 2D images of polarized PMNs might be due to an actual concentration of F-actin in privileged areas, to a local concentration of plasma membrane drawing filamentous actin or to variations in the cell volume. Then, we studied the distribution of a cytoplasmic marker, fluorescein diacetate and a membrane probe, TMA-DPH, in unstimulated rounded PMNs and in spherical and morphologically polarized PMNs stimulated by formylpeptide. The distribution of neither of these probes was correlated with F-actin distribution, especially in rounded PMNs stimulated 30 s with 10(-8) M fMet-Leu Phe, suggesting that F-actin was concentrated in two foci located in the cell head region and in the cell posterior end. In addition, zymosan-activated serum induced the morphological polarization of PMNs and the appearance of two foci of filamentous actin, demonstrating that binding of formylpeptide to its specific receptor was not required for F-actin reorganization. We conclude that the accumulation of F-actin probably resulted from local filament assembly and put forward the hypothesis that microfilament reorganization in two centres drives the morphological polarization of PMNs. PMID- 1429901 TI - A gene family consisting of ezrin, radixin and moesin. Its specific localization at actin filament/plasma membrane association sites. AB - Radixin is a barbed end-capping actin-modulating protein which was previously reported to be concentrated at cell-to-cell adherens junctions (AJ) and cleavage furrows. Recently, cDNA encoding mouse radixin was isolated, showing that radixin is highly homologous to but distinct from ezrin. From mouse teratocarcinoma cells we isolated and analyzed cDNA encoding another radixin-related protein. Sequence analysis has demonstrated that this protein is a mouse homologue of human moesin (98.3% identity) and that it shares 71.7% and 80.1% identity with ezrin and radixin, respectively. Translation experiments in vitro combined with immunoblot analyses led us to conclude that there is a gene family consisting of ezrin, radixin and moesin. These members are coexpressed in various types of cells. Then, by immunofluorescence microscopy, we closely analyzed their distribution using polyclonal and monoclonal antibodies, which could recognize all three members. In addition to cell-to-cell AJ and cleavage furrows, it was shown that they were concentrated at microvilli and ruffling membranes in various types of cells. Furthermore, the cell-to-substrate AJ (focal contacts) were clearly stained by anti-radixin pAb only after the apical/lateral membranes and cytoplasm were removed by the zinc method. We conclude that at least one of the members of the ezrin-radixin-moesin family is concentrated at specific regions where actin filaments are densely associated with plasma membranes. PMID- 1429904 TI - Association of myosin with the connecting cilium of rod photoreceptors. AB - The cilium of a vertebrate photoreceptor cell connects the phototransductive outer segment of the cell to the inner segment. Previous studies have shown that, within the connecting cilium, there is a small cluster of actin filaments, which play a critical role in the formation of new disk membranes. Here, we have detected a polypeptide in rat rod outer segments that is recognized by myosin heavy chain antibodies and was found to possess other characteristics of conventional non-muscle myosin heavy chain: it comigrates in SDS-PAGE with non muscle myosin heavy chain; it associates with the cytoskeleton of rod outer segments in an ATP-sensitive manner; and it binds to purified actin filaments in the absence of ATP. Myosin ATPase activity was also detected in isolated rod outer segments. Electron immunomicroscopy revealed that myosin is present in the small actin-containing domain within the connecting cilium at the site of disk membrane morphogenesis. These results pose the possibility that an actin-myosin contractile mechanism functions in the formation of new photoreceptor disk membranes. PMID- 1429903 TI - Tubulin in bovine retinal rod outer segments. AB - Bovine rod outer segment (ROS) preparations contain a major 58 kDa protein doublet that was identified by immunoblot as tubulin. Quantification by gel densitometry showed that the total amount of tubulin was 5- to 10-fold higher than that attributable to the rod axoneme, suggesting additional role(s) for tubulin in photoreceptor cells. Approximately 20% of this nonaxonemal tubulin (15% of total tubulin) is tightly associated with outer segment membranes. This fraction remains membrane-associated after extensive low- or high-salt washing, requiring detergents or protein denaturants for release from ROS membranes. Unlike ROS soluble tubulin it associates tightly with liposomes upon detergent solubilization and reconstitution. The ROS membrane-associated tubulin is highly enriched in isolated ROS plasma membrane fractions compared to the total outer segment membrane pool and can be localized to the plasma membrane but not to disks by immunofluorescent staining, suggesting a possible role in the structure or electrophysiology of the rod outer segment plasma membrane. PMID- 1429905 TI - Radial movement of lysosomes along microtubules in permeabilized macrophages. AB - In murine bone marrow-derived macrophages, lysosomes often form tubulovesicular compartments, whose extended distribution in the cytoplasm depends on the integrity of cytoplasmic microtubules. When macrophages with fluorescently labeled lysosomes were plated onto coverslips opsonized with IgG, they engaged that surface in a phagocytic response (frustrated phagocytosis). The tubular lysosomal compartment of these cells collected in a central, perinuclear region, despite the continued presence of a radiating array of cytoplasmic microtubules. Using methods developed in the study of melanophores, we permeabilized macrophages engaged in frustrated phagocytosis, then re-activated lysosome extension along microtubules. Permeabilization was selective for plasma membranes, in that high molecular weight probes such as trypan blue or IgG could enter cells, while fluorescent probes previously loaded into lysosomes via endocytosis remained contained therein. Addition of 2 mM ATP, GTP or UTP to these permeabilized cell models produced centrifugal extension of tubular lysosomes. Selective depletion of ATP, using Escherichia coli glycerol kinase, inhibited ATP dependent extension but not that which occurred with GTP or UTP, indicating that the mechanism of radial movement can use any of these three nucleotide triphosphates. Extension was independent of pH between 6.8 and 7.4, and was inhibited by AMP-PNP and by GMP-PNP. Depolymerization of cytoplasmic microtubules with nocodazole prevented subsequent ATP-inducible lysosome extension, whereas preincubation of cells with cytochalasin D did not inhibit the response. These results are consistent with the in vitro mechanochemical properties of kinesin (Cohn et al., 1989), and support earlier evidence, obtained in living cells, that kinesin is the mechanochemical motor of lysosome extension along microtubules in macrophages. PMID- 1429906 TI - Characterization of early and late endocytic compartments of the transferrin cycle. Transferrin receptor antibody blocks erythroid differentiation by trapping the receptor in the early endosome. AB - We describe a detailed morphological characterization of the endocytic pathway in differentiating chicken erythroblasts transformed by a temperature-sensitive mutant of avian erythroblastosis virus (AEV). These cells express high levels of transferrin receptors (TfR) when induced to differentiate at 42 degrees C. Biochemical analysis showed that most (approximately 90%) of the internalized 125I-Tf recycled within approximately 30 min while a smaller fraction of 125I-Tf required up to 2 h for recycling. By immunocytochemistry, the bulk of Tf and TfR was localized at the plasma membrane and in tubuloreticular early endosomes. This structure contained coated buds that labelled with an antibody specific for the clathrin light chain. Decreasing amounts of both Tf and TfR were detected in two distal compartments, spherical endosome vesicles resembling multivesicular bodies and the prelysosomal compartment (PLC) enriched in cation-independent mannose 6 phosphate receptor. As shown by fluorescent (FITC-Tf) labelling of living cells, the movement of Tf/TfR complex into these late structures was accompanied by a significant drop in pH from about 6, the value displayed by early endosomes, to values below pH 5.0. Since no detectable 125I-Tf degradation was observed during a 4 h period we believe that the Tf/TfR detected in these late endocytic structures avoids degradation and recycles back to the cell surface. The addition of an anti-TfR monoclonal antibody to the culture medium of these cells blocks their differentiation. Under this condition the antibody-TfR complex was trapped in an early endosome compartment that enlarged to more than twice its normal size. However, this condition did not affect the transport kinetics of horseradish peroxidase from the medium to the PLC. PMID- 1429907 TI - Development and characterisation of a rat brain capillary endothelial culture: towards an in vitro blood-brain barrier. AB - Primary culture of rat brain endothelial cells is described, based on the method of C. C. W. Hughes and P. L. Lantos. The cells have been characterised using morphological and immunocytochemical techniques, and systematic studies undertaken to determine the optimal culture medium and conditions required to grow the cells at high purity on a variety of substrata. The endothelial cells have a spindle-shaped morphology, and proliferate as plaques from small clusters of cells associated with capillary fragments in the starting material. Tight junction-like cell:cell appositions are seen at the electron-microscopic level. The cells show characteristic staining for antigens recognized by antibodies against von Willebrand factor (Factor VIII-related antigen), angiotensin converting enzyme (ACE), the transferrin receptor (Ox-26), actin and vimentin. They also show binding of the lectin from Ulex europaeus (UEA I). Potential contaminating cells include smooth muscle, fibroblasts, pericytes and meningeal cells. Contaminants can be kept to < ca. 5% by careful removal of large vessels and meninges during dissection, by brief treatment with Ca(2+)- and Mg(2+)-free saline, by growth in medium supplemented with plasma-derived serum treated for removal of platelet-derived growth factor (PDGF), and by occasional use of medium in which D-valine is substituted for L-valine. Cells attach well to collagen coated plastic, less well to glass. Cells can be grown on transparent collagen filters (ICN, Cellagen and Costar, Transwell-Col), and on microcarrier beads (Pharmacia, Cytodex-3). The culture has proved to be a useful preparation for studies of cellular physiology, pharmacology and biochemistry of the brain endothelium, and represents a first step in producing an in vitro model of the rat blood-brain barrier. PMID- 1429908 TI - Integrin subunit expression by human osteoblasts and osteoclasts in situ and in culture. AB - The extracellular matrix may be considered as an insoluble local mediator which plays an important role in regulating cell function. Communication between the cell and its matrix occurs via the integrins, a family of transmembrane proteins composed of non-covalently linked alpha and beta subunits. The aim of this study was to establish which integrins are present on human bone cells in situ and in culture, using cryostat sections of undecalcified human bone, osteoclastoma tissue and cultured human osteoblasts. Integrin subunit expression was identified indirectly using alkaline phosphatase anti-alkaline phosphatase conjugates and FITC-labelled secondary antibodies. Subunits expressed by cultured human osteoblast-like cells were then quantified by FACS analysis. Staining patterns observed in situ show that osteoblasts and osteoclasts possess different integrin subunits. Osteoblasts primarily express alpha 1, alpha 3 and beta 1 and weakly express alpha 2. Osteoclasts express alpha 2, alpha V, beta 1 and beta 3. Subunits alpha 4, alpha 5, alpha 6, alpha L, alpha M and beta 2 were not expressed by either of these cell types. Expression of beta 1 by all cells of the osteoblastic lineage was constitutive, but alpha 1 and alpha 3 subunits were expressed by osteoblasts actively synthesizing bone and some of the osteoblast lining cells. All integrin subunits identified on osteoblasts in situ were maintained on culture but there was an increased expression of alpha 2 and alpha V subunits were weakly positive. Expression of alpha 2, alpha 3, alpha V and beta 1 subunits was independent of cell density but expression of alpha 1 was much greater in confluent cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1429909 TI - Cell guidance by micropatterned adhesiveness in vitro. AB - Tracks of adhesiveness are believed to be involved in guiding morphogenetic cell migrations. Here, electronics microfabrication technology was used to manufacture patterns of alternating tracks of adhesive and non-adhesive substratum (untreated fused quartz and adjacent parallel tracks of hydrophobic treatment) of varying period (4, 6, 12, 24 and 50 microns). These experimental substrata were used to model, in vitro, possible differentially adhesive guidance cues. The effect of such patterned substrata was assessed using fibroblastic BHK cells and epithelial MDCK cells. Cells were oriented and elongated by these surfaces. Their responsiveness was dependent on cell type, cell-cell interactions, and the geometry of the patterns. Alignment of BHK cells increased with increasing pattern period. Single MDCK cells aligned to all pattern periods, their elongation being period-dependent, whereas colonies were mainly unaffected. These in vitro data have important implications, which are discussed with regard to in vivo guidance cues. The ability of cells to bridge over non-adhesive regions will influence the effectiveness of linear cues, and will be important for guideposting. The geometry of patterns of differential adhesion is here shown to be an important factor in determining the precision with which local guidance of cells may be controlled. PMID- 1429910 TI - The role of the cytoskeleton and intercellular junctions in the transcellular membrane protein polarity of bovine aortic endothelial cells in vitro. AB - This project examines the transcellular membrane protein polarity of bovine aortic endothelial cell (BAEC) monolayers in vitro with respect to the roles that intercellular junctions (as defined by comparing confluent and subconfluent monolayers) and the submembranous cytoskeleton play in controlling this phenomenon. Plasma membrane (PM) proteins obtained from apical (AP) and basolateral (BL) PM domains of confluent BAEC monolayers were isolated using the cationic colloidal silica technique and resolved by two-dimensional gel electrophoresis (2-D PAGE). To facilitate the identification of domain-specific PM proteins, an isoelectric point/molecular weight database of the proteins from AP and BL PM domains was constructed. Domain-specific PM proteins were assessed for their interaction with the cytoskeleton by determining whether they co isolated with a Triton X-100 detergent-resistant cytoskeletal/extracellular matrix fraction. The maintenance of polarized PM protein segregation by intercellular junctional complexes was determined by comparing AP and BL protein patterns of confluent monolayers with patterns generated by subconfluent monolayers, which lack such junctional structures. Proteins isolated from AP and BL PM domains from both confluent states were immunoblotted with antibodies to angiotensin-converting enzyme (ACE) and collagen receptors (CR). ACE was restricted exclusively to the AP PM domain in the subconfluent condition, even though no apparent cytoskeletal interaction was observed. CRs, found to interact with the cytoskeleton in either confluence state, were predominantly segregated to the BL PM domain regardless of the presence or absence of cell-cell contact. Membrane proteins found by 2-D PAGE to be asymmetrically distributed in the absence of intercellular junctions were assessed for cytoskeletal interaction by their inability to be extracted by Triton X-100 from monolayers in the subconfluent state. Computer cross-referencing of 2-D PAGE peak lists and immunodetection generated from the above fractionation protocols identifies a set of four proteins associated with the cytoskeleton that remain segregated in the proper domain, and five proteins associated with the cytoskeleton that become equally distributed between AP and BL PM domains in the absence of intercellular junctions. Additionally, six proteins not associated with the cytoskeleton remain asymmetrically distributed to the AP domain in the subconfluent state. The data suggest that BAEC monolayers have unknown mechanisms, apart from intercellular junctions expressed at confluency or cytoskeletal binding, for maintaining transcellular PM protein polarity. PMID- 1429911 TI - Dimeric transcription factor families: it takes two to tango but who decides on partners and the venue? AB - Dimeric transcription factors that bind to DNA are often grouped into families on the basis of dimerization and DNA-binding specificities. cDNA cloning studies have established that members of the same family have structurally related dimerisation and DNA-binding domains but diverge in other regions that are important for transcriptional activation. These features lead to the straightforward suggestion that although all members of a family bind to similar DNA elements, individual members exhibit distinct transcriptional effector functions. This simple view is now supported by experimental evidence from those systems that have proved amenable to study. There are however some largely unaddressed questions that concern the mechanisms that allow family members to go about their business without interference from their highly related siblings. Here I will discuss some insights from studies of the bZIP class of transcription factors. PMID- 1429912 TI - Who's minding your genes? PMID- 1429913 TI - Recent advances in the treatment of otitis media. AB - Otitis media (OM) continues to be a major cause of morbidity in infants and children. Antibiotics are presently the mainstay of treatment. A variety of agents including vaccinations against the most common causative organisms, prednisone, non-steroidal anti-inflammatory agents, intravenous immune globulin, antihistamines, decongestants, and topical antibiotics have been investigated. This review will address the recent developments in the treatment and prevention of OM. PMID- 1429914 TI - Progress in self treatment for psoriasis vulgaris. AB - Chronic plaque psoriasis is by far the most frequent form of the disease and is usually amenable to home treatment. The therapeutic armamentarium for self treatment of psoriasis has, until recently, been limited to emollients, tar, dithranol and topical corticosteroids. Although limited progress has been made in improving formulations and treatment regimes for these compounds, they still have significant drawbacks in terms of either unwanted effects or cosmetic acceptability. Topical vitamin D analogues offer a new, effective, convenient and safe option for self-treatment of psoriasis. Most research has been performed on calcipotriol. This has compared well to beta-methasone valerate and short-contact dithranol in controlled studies. Skin irritation is frequently noticed by patients, but rarely requires treatment to be discontinued. The mechanism of action appears most likely to be a direct regulation of keratinocyte proliferation and differentiation. Calcipotriol has relatively little effect on calcium metabolism and appears to be safe when used according to established guidelines but hypercalcaemia may develop if excessive quantities are used. PMID- 1429915 TI - Sorption studies of dipotassium clorazepate salt (Tranxene) and midazolam hydrochloride (Hypnovel) in polyvinyl chloride and glass infusion containers. AB - The compatibilities of dipotassium clorazepate and midazolam hydrochloride with polyvinyl chloride (PVC) bags have been studied and compared with those observed with glass flasks. At room temperature, dipotassium clorazepate showed chemical instability which was independent of the container. At 4 degrees C, dipotassium clorazepate showed no decrease in concentration over 12 h, both in 5% dextrose solution and 0.9% sodium chloride solutions. When stored for longer periods of up to 72 h, a slight decrease not exceeding 5% was observed. The compatibility of midazolam with the PVC bags was found to be good at room temperature. It was slightly better in 5% dextrose solution than in 0.9% sodium chloride solution. High sorption of the drug was observed at pH 7.0 when the primary ring structure is maintained. The results make it possible for the hospital pharmacist to prepare dipotassium chlorazepate salt and midazolam admixtures up to 3 days before administration, provided the former are stocked in a refrigerator and the latter are prepared in dextrose isotonic solutions. PMID- 1429916 TI - Pilot study to compare the bronchodilator and metabolic responses to terbutaline infusion in seven asthmatic subjects--are they correlated? AB - We compared the changes in peak expiratory flow rate (PEFR), plasma potassium and plasma glucose during and after an infusion of the beta 2-agonist, terbutaline, in seven asthmatic subjects. Our aim was to establish whether these metabolic parameters could be correlated with PEFR. The percentage changes in PEFR were significantly correlated with the percentage changes in glucose (r = 0.60, P less than 0.001) and potassium (r = -0.64, P less than 0.001). Values for glucose and potassium changes were also correlated significantly with each other (r = 0.86, P less than 0.001). This suggests that in asthmatic subjects on beta 2-agonist treatment, plasma potassium could be used as a surrogate marker for beta 2 activity at bronchi. It also implies that the most effective beta 2-agonist bronchodilators will produce the greatest fall in plasma potassium. Further studies with a larger number of patients are needed to confirm this. PMID- 1429917 TI - Determination of dissociation constants of some pharmaceutical compounds using derivative spectrophotometry. AB - Derivative spectrophotometry is applied to the determination of the dissociation constants (pKa) of some weakly dissociating compounds. The pKa value(s) can be calculated by measuring the amplitude of derivative maxima (D) at the selected wavelengths for the dissociated, undissociated and partially dissociated forms of the compound. A graphical technique, based on plotting the derivative spectrophotometric titration curves and interpolating pKa at D1/2 is also presented. Both methods are applied to pharmaceutical compounds with single and double dissociation constants. The results are in good agreement with the reported pKa values of the investigated compounds. PMID- 1429918 TI - A survey of prescription label preferences among community pharmacy patrons. AB - Fifty-five randomly selected community pharmacy patrons were surveyed regarding their preferences between four different prescription labels. The variables displayed on the four labels were: (i) laser printed, (ii) dot-matrix printed, (iii) glossy surface, and (iv) matt surface. The study population was stratified by age and gender. Statistical analysis of the results indicated a clear preference by all groups for the laser printed labels (P less than 0.001), and the only other statistically significant finding was the preference for the matt surface (P less than 0.05) of females between the ages of 16 and 39. The implications for these differences on label readability are discussed, and recommendations are offered for the use of improved laser technology for computer generated prescription labels. PMID- 1429919 TI - Development of a stable oral liquid dosage form of spironolactone. AB - A clear, stable, oral liquid dosage form of spironolactone has been developed. Solubility profiles of spironolactone were obtained in several co-solvent blends. Using this data, a co-solvent blend containing polyethylene glycol 400 (30% v/v), propylene glycol (10% v/v), glycerin (10% v/v) and ethyl alcohol (10% v/v) was used to solubilize spironolactone at a concentration of 2 mg/ml. The final formulation contained sweetening agents (sucrose, saccharin sodium), flavours (cherry, sweet), a desensitizing agent (menthol), a dye (FD&C Red #40) and a preservative (benzoic acid) to incorporate the desired organoleptic and preservative properties. A phosphate buffer was used to maintain a pH value of 4.5 (pH of maximum stability as reported earlier) to minimize hydrolysis. The final dosage form was stable for at least 93 days at 40 degrees C (loss of potency less than 4%). According to FDA guidelines, a tentative expiration date of 2 years at 25 degrees C is justifiable. PMID- 1429920 TI - Influence of age and co-medication on steady-state phenobarbital serum level-dose ratios in Japanese paediatric patients. AB - The effects of age and co-medication on steady-state phenobarbital (PB) level dose (L/D) ratios were evaluated retrospectively in 539 paediatric patients. The PB L/D ratio increased significantly with age up to 15 years. Associated anti epileptic therapy affected the PB L/D ratio, which was significantly increased in patients on polypharmacy as compared to patients on monopharmacy. Therefore, routine monitoring of PB serum levels is extremely useful, particularly in the paediatric age group, and in patients who require associated anti-epileptic medication. PMID- 1429921 TI - [Value an immediate histological study of the lymph nodes at the time of surgical treatment of cancer of the uterine cervix]. AB - From 1978 to 1989, 500 external iliac lymph node dissections were carried out at the Institut Curie during surgery for cancers of the uterine cervix. The percentage of error of the histological study of the lymph node was 2.8%, including 13 false-negative findings and 1 false-positive. In 1.8% of cases (9), there were doubts as to lymph node invasion, and no confirmation was possible. The most frequent cause of error was the failure to recognize partial invasion of a lymph node. Fibrosis and necrosis secondary to preoperative radiation therapy make the intraoperative histological study more difficult. PMID- 1429922 TI - [Linitis plastica of the proximal part of the duodeno-jejunal angle. Apropos of a case]. AB - The authors report the first case to date of primary linitis plastica localised to the proximal part of the small bowel. A 44-year-old man with a one-month history of vague abdominal symptoms was treated for a proximal jejunum perforation due to a linitis plastica and died 2 months later. PMID- 1429923 TI - [Intestinal ascariasis. A rare cause of obstruction of the small intestine]. AB - Ascariasis is a benign and common disease in tropical areas. Due to its endemicity and high prevalence, serious abdominal complications requiring urgent and versatile surgical therapy do occur. An observation of intestinal obstruction by ascaris bundle, diagnosed during operation, is reported. The postoperative course was uneventful. PMID- 1429924 TI - [Gunshot wounds of the ureter]. AB - Lesions of the ureter caused by penetrating wounds of the abdomen rare a are complication of abdominal gunshot wounds, of which the reported incidence is 2 to 17%. The preoperative diagnosis is difficult and unrecognized initially in every third case. There are no early clinical signs of ureteral lesions. There is often no hematuria. Only IVP can make the preoperative diagnosis possible. As a matter of fact, the diagnosis will often be established by the surgical exploration made during the laparotomy required by the extent of the associated lesions. The ureteral blast contusion is an important cause of secondary necrosis with fistula. The treatment is mainly based on ureteroureterostomy after debridement. The transanasmotic drainage of urine is controversial. Mortality results from associated abdominal lesions and morbidity consists in a risk of secondary nephrectomy. PMID- 1429925 TI - [Volvulus of the sigmoid colon. Emergency resection and anastomosis]. AB - Eleven cases of sigmoid volvulus in patients aged 76 years in average, without visible signs of necrosis on endoscopy, are reported. All patients were treated within 6 to 48 hours by colic resection and immediate restoration of continuity with a mechanical anastomosis. Morbidity was low, including one case of evisceration and one of pneumonia, and there was no mortality after three months. Early resection seems to prevent the risks of necrosis and recurrence, and to have a good prognosis for survival. PMID- 1429926 TI - [Cockett's syndrome caused by an ectopic kidney. Apropos of two cases]. AB - Two original cases of Cockett's syndrome caused by an ectopic and/or malformed kidney are reported. Intravenous pyelography and computed tomography allow establishing the diagnosis. The choice of the therapy depends on the patency of the left common iliac vein. PMID- 1429927 TI - [Intestinal invagination in adults. Apropos of a case of idiopathic ileocolic invagination]. AB - Intestinal intussusception is a rare condition in adults, in whom it is caused by an organic lesion in 60% of all cases. On the basis of one case of ileocolic intussusception in a 64-year-old patient, the author reviews the literature and sums up the clinicopathological data, as well as the elements of the clinical diagnosis and, most importantly, of the radiological diagnosis for which enema with hydrosoluble contrast media is the method of choice. The treatment mainly consists in intestinal resection with anastomosis. PMID- 1429928 TI - [Idiopathic segmental infarction of the greater omentum. Apropos of a new case]. AB - Idiopathic segmental infarction of the greater omentum is an unusual cause of acute abdomen. The preoperative diagnosis is difficult. Before laparotomy the diagnosis is hardly ever considered; the authors report a personal case and describe etiologic hypotheses and the clinical picture of this disease. PMID- 1429929 TI - [Arthroscopy of the shoulder]. AB - Arthroscopy of the shoulder is currently gaining importance because of the diagnostic aid it can provide to understand the pathology of this complex joint, and also because of the technical possibilities it offers for treatment. From a diagnostic point of view, it has allowed, for example, a better understanding of the anatomical lesions observed in instability, or a better analysis of partial rotator cuff lesions. The therapeutic possibilities are the reason for the current enthusiasm for this endoscopic technique: removal of a foreign body, articular washing, synovectomy, ligament reinsertion of abrasion are now accessible with some training. The two indications of shoulder arthroscopy that are most resorted to are the endoscopic treatment of some cases of shoulder instability with reinsertion of disinserted elements at the anterior capsular ligamentous level, and anterosuperior decompression of the rotator cuff when there is a conflict between this tendinous area and the acromiocoracoid osteoligamentous dome. PMID- 1429930 TI - [Iliac eventration after posterior iliac bone removal. An original technique of reconstruction]. AB - A tricortical bone graft removal from the iliac crest causes a parietal defect that may be complicated by iliac or iliolumbar eventration, according to the extent of the bone loss. On the basis of their experience with a particularly characteristic clinical case, the authors describe an original reconstruction technique. The surgical techniques aimed at parietal restoration described in the literature include either the use of foreign materials or of those provided by the patient (skin, fascia lata, etc.), or the use of the surrounding anatomical elements to reconstruct a solid wall. Most of these procedures may be difficult to implement if the loss of substance is extensive, or in a posterior site. Thus, in order to prevent possible recurrence in case of major bone defects, we propose to combine the cure of the eventration with a restoration of bone continuity with a cold-conserved allograft and the reconstruction of the musculoaponeurotic curtain by the translation of the lumbosacral fascia. This procedure allowed obtaining a very satisfactory result, which was stable after 18 months both as regards parietal reconstruction and as regards pain, owing to the restoration of balance in the paraspinal muscular support. PMID- 1429931 TI - [Technique of percutaneous drainage under ultrasound guidance for acute cholecystitis]. AB - Gallbladder percutaneous drainage under ultrasound guidance could offer an interesting option compared to surgery in multi-systemic disease patients with acute cholecystitis and who are considered as high-risk patients towards anesthesia and surgery. The authors describe this technics which is an easy, quick and eventually repetitive procedure with no major complications. PMID- 1429932 TI - [Spigelian hernia and common mesentery. Apropos of a case]. PMID- 1429933 TI - Accuracy in establishing identity in edentulous individuals by means of intraoral radiographs. AB - The aim of this study was to evaluate the degree of accuracy in establishing identity in edentulous individuals by using occlusal "ante- and postmortem" radiographs of the maxilla. Twelve examiners with the following background; six dental radiologists, four other specialists in dentistry and two dental students were asked to combine the radiographs. The results showed that six of the 12 observers were able to correctly establish identity for all 20 cases. Five of these observers were dental radiologists and one of them was a prosthodontist. The other specialists made 3-8 identifications. The senior and the junior dental students made two and four incorrect identifications. The findings from this study emphasise the importance of having more than one forensic specialist signing the identification form. The results also indicate that examiners well trained in oral radiology are able to determine a positive identity even in cases where the teeth are not present. PMID- 1429934 TI - Dental identification after the Dash 7 aircraft accident at Torghatten, Northern Norway, May 6th, 1988. AB - The accident occurred when a Dash 7 aircraft hit a steep mountain side and fell approximately 70 meters. A fire broke out immediately and all 33 passengers and three crew members perished. Most of the victims were found in or near the wreckage and burnt by the fire. The identifications were carried out by the Norwegian Identification Commission which included four dentists. One dentist, together with a pathologist, co-operated with the police at the site of the accident. All 36 victims were identified and in 32 cases (89%) dental identity was established. This success was mainly due to systematic radiographic recordings of the victims and a comparison with ante-mortem radiographs. The Norwegian computer programme for identification was successfully tested during this investigation. PMID- 1429935 TI - International co-operation in a dental identification. AB - A case of international identification of an unknown male, where the teeth were essential in establishing identity is described. A noteworthy aspect of the procedure was the teamwork between the police and other authorities, and the forensic odontologist and medical examiners in Albania and Sweden. In Albania a forensic medical examiner handled the dental examination, since forensic odontology is not yet acknowledged. The importance of having dental and medical ante-mortem registers for missing persons in every country is stressed. This is best administered in co-operation with the police authorities. PMID- 1429936 TI - Exhumation following incorrect identification. A case report. AB - The exhumation of two victims of a light aircraft accident was performed in February 1991 at Oudtshoorn, Cape. The exhumation was ordered by the magistrate on request of the parents of one of the victims who suspected that their son had been wrongly identified at the postmortem examination. At the pre-burial autopsy all the victims were positively identified, but the identity of two of the victims was subsequently reconsidered and reversed because one of them wore a silver bracelet. Burial then took place. The exhumation was ordered one month after the accident at which stage the bodies were in an advanced state of decomposition. Oral autopsies were performed on each of the victims, the jaws were radiographed and postmortem dental records drawn up. Dental records were obtained from the dentists who treated them and the information from these records was used to draw up ante-mortem dental records. A comparison between the postmortem and ante-mortem records showed that the victims were incorrectly identified and reburial in the correct graves was subsquently carried out. This case again emphasies the importance of dental identification in cases of severe burning, multilation or decomposition in order to avoid mistaken identity and incorrect burial in the future. PMID- 1429937 TI - A not-so-distant mirror. PMID- 1429938 TI - Animal research--sensibilities and sense. PMID- 1429939 TI - Healthcareopathy: a multifactorial disease. PMID- 1429940 TI - Prevention of sudden cardiac death. AB - Since the vast majority of these deaths are triggered by arrhythmias, the first step in prevention is to understand the risk factors for malignant rhythms. The second is to identify patients who may benefit from preventive intervention. Finally, who should get drugs, who automatic cardioverter-defibrillator implantation. The determinants of that choice remain to be elucidated. PMID- 1429941 TI - Management of HIV infection: a summary of summaries (I). AB - Often the hardest task in managing HIV-infected patients is keeping up-to-date on the latest in HIV care. Presented here is a summary of 32 current, accessible articles for the primary care physician. PMID- 1429942 TI - Long-term survival in primary pulmonary hypertension. PMID- 1429944 TI - Where have all the good cases gone? PMID- 1429943 TI - Acute myocardial infarction or pericarditis? PMID- 1429945 TI - Painful ophthalmoplegia in a patient with SLE. PMID- 1429946 TI - Coronary heart disease in women: a 'new' problem. AB - Recent reports of "sex bias" in the management of heart disease serves to focus on a more fundamental problem. Too little is known about the biology of heart disease in women or the reasons for striking differences in women's risks, prognosis, and treatment outcome--medical or surgical. Studies more sharply focused on these issues could improve treatment for half of the patient population. PMID- 1429947 TI - The acquisition of Italian morphology: implications for models of language development [see comment]. AB - This study explores the spontaneous acquisition of Italian inflectional morphology by three children (age range I;4-3;O). Longitudinal, free speech samples are examined, focusing on the development of the morphological paradigms of Italian verbs, pronouns and articles. Data analysis is conducted using criteria appropriate to allow reliable cross-linguistic comparisons with data from English. By this means we evaluate the plausibility of a nativist, parameter setting account of language development in Italian and English, as recently proposed for these two languages. Results show that the general developmental patterns observed in Italian are not significantly different from those found in English. These findings are not consistent with current interpretations of parameter-setting accounts of language development. Alternative explanatory models are discussed. PMID- 1429948 TI - Comprehension and production of gesture in combination with speech in one-word speakers. AB - This study explores the role that gesture plays in the earliest stages of language learning. We describe how one-word speakers use gesture in combination with speech in their spontaneous communications, and interpret gesture presented in combination with speech in an experimental situation. Forty one-word speakers (ages 1;2.22 to 2;4.6) were videotaped in a free-play session which provided data on the child's spontaneous gesture and speech production. The children were also given a comprehension task in which the presence and absence of gesture were systematically varied in relation to speech. We found that (1) all of the children spontaneously produced gestures in combination with speech, and (2) all of the children were able to understand gesture when it was presented in combination with speech, not only when the gesture was redundant with speech but also when the gesture substituted for speech. These data suggest that, even at this young age, gesture naturally forms an integrated system with speech in both production and comprehension. PMID- 1429949 TI - Discourse and the acquisition of eat. AB - English has several classes of transitive verbs which can optionally appear without an undergoer. Despite their similar syntactic subcategorization, there are at least three different semantic subclasses that allow undergoer omission. Information sources based on surface structure, for example, syntactic bootstrapping, cannot inform the child of the semantic representation of these verbs. The focus of this paper is the acquisition of a single English verb, eat. The transcripts of 40 children, who were audiotaped monthly from 1;0 to 3;0, showed that eat was the first member of this verb class to be acquired. Some 1276 eat sentences were analysed for the presence of overt undergoer arguments across levels of cumulative verb lexicon (CVL) size, and two discourse conditions: (1) UNDERGOER ACCESSIBLE and (2) OPEN (to undergoer omission). Results indicate that undergoer omission became associated with discourse conditions when CVL size rose above 75 types, at MLU approximately 2.4 and age approximately 2;3. This suggests that two-year-old children are sensitive to a relationship between undergoer omission and discourse context. PMID- 1429950 TI - Phonological characteristics of words young children try to say. AB - To examine the possible persistence of phonological selectional constraints on young children's lexical choices, the words attempted in the conversational speech of a longitudinal sample of 12 normally-developing preschoolers from age 2;0 to 5;0 were scored for syllabic length, presence of consonant clusters, and distribution of constituent phonemes. Except at the youngest ages, few developmental changes in target word characteristics were seen, and the observed differences were largely accounted for by syntactic, lexical, and pragmatic factors. The results suggest that selectional constraints persist only briefly in the course of language acquisition. PMID- 1429951 TI - Mental terms in mothers' and children's speech: similarities and relationships. AB - In this study, mental terms in mothers' and their children's speech at two and three years of age were studied in order to examine the relationships between maternal and child use. Nineteen mother and child dyads were videotaped for one hour on each of two days when the children were 2;0 and again for two one-hour sessions on separate days when they were 3;0, and mental terms were noted. The utterances in which mental terms were used were coded for function. Results supported the existing picture of children's mental term use. Few terms appeared at 2;0, but many were used at 3;0 with think and know predominating. Mental terms occurred more commonly in utterances used to regulate the interaction between the participants than in utterances referring to mental states. Children's mental term use mirrored that of their mothers. Further, mothers' use of mental terms for particular functions when their children were 2;0 predicted their children's use at 3;0. While allowing no conclusions about causation, our findings suggest that the development of mental state language, and thus presumably a theory of mind, is fostered by the linguistic environment. Specifically, it is argued that the tendency of mothers to focus their children's attention on mental processes by talking about them and, more importantly, by using utterance types which conceivably direct the children to reflect on their own mental states, is associated with children's use of mental terms. PMID- 1429952 TI - Can bilingual two-year-olds code-switch? AB - Sociolinguists have investigated language mixing as code-switching in the speech of bilingual children three years old and older. Language mixing by bilingual two year-olds, however, has generally been interpreted in the child language literature as a sign of the child's lack of language differentiation. The present study applies perspectives from sociolinguistics to investigate the language mixing of a bilingual two-year-old acquiring Norwegian and English simultaneously in Norway. Monthly recordings of the child's spontaneous speech in interactions with her parents were made from the age of 2;0 to 2;7. An investigation into the formal aspects of the child's mixing and the context of the mixing reveals that she does differentiate her language use in contextually sensitive ways, hence that she can code-switch. This investigation stresses the need to examine more carefully the roles of dominance and context in the language mixing of young bilingual children. PMID- 1429953 TI - The development of children's knowledge structures: events, slots, and taxonomies. AB - Seventeen preschool (age range 2; 10-3;6), 26 kindergarten (age range 5;5-6;7), and 26 fourth-grade (age range 9;5-10;5) children's knowledge structures were examined with a word association task and a match-to-sample picture task to determine whether or not children used slot-filler categories as a mediating structure between event-based and taxonomic knowledge structures, as proposed by Nelson (1985, 1986). In general, preschool children were able to provide event based, but not slot-filler or taxonomic, relations; kindergarten children were able to provide event-based or slot-filler relations, but very few taxonomic relations; and fourth-grade children were able to provide all three relations. These findings support Nelson's hypothesis that taxonomic knowledge structures are derived from event-based knowledge structures with the aid of slot-filler categories. PMID- 1429954 TI - Interpreting and responding to spoken language: children's recognition and use of a speaker's goal. AB - This study had two purposes. The first was to examine age differences in the extent to which children infer and use a speaker's interpersonal goal to understand speech acts. To this end, the subjects responded to Do you have...? requests in a role-playing task. The goal behind such a request is implicit in the speaker's choice of noun phrase. We sought to determine whether children, like adults, use the noun phrase to infer the speaker's goal and thereby decide whether the request is a yes-no question or a directive. The second purpose was to examine age differences in the extent to which children select responses that carry implications appropriate to the speaker's interpersonal goal. To do this, Do you have...? requests containing general category labels were addressed to the children when they possessed all the category exemplars and when they possessed only a few exemplars. A simple yes implies that the listener has nearly all exemplars and, therefore, is inappropriate for the speaker's goal in the latter situation. The subjects were six-, seven-, nine-, and eleven-year-olds and adults, with 12 subjects per age. Only the eleven-year-olds and the adults used the speaker's noun phrase and considered the implications of yes. PMID- 1429955 TI - Morphosyntactic development in Italian and its relevance to parameter-setting models: comments on the paper by Pizzuto & Caselli. AB - Pizzuto & Caselli (1992) claim that data from the morphosyntactic development of Italian-speaking children are inconsistent with nativist, parameter-setting models of language development. In the present Note it is argued that much of the data which Pizzuto & Caselli adduce is irrelevant to the specific hypotheses they are evaluating and that those data which are relevant fully support parameter setting and linguistic-theoretic models, contrary to their claims. PMID- 1429956 TI - The Human Communication Research Centre dialogue database. AB - The HCRC dialogue database consists of over 700 transcribed and coded dialogues from pairs of speakers aged from seven to fourteen. The speakers are recorded while tackling co-operative problem-solving tasks and the same pairs of speakers are recorded over two years tackling 10 different versions of our two tasks. In addition there are over 200 dialogues recorded between pairs of undergraduate speakers engaged on versions of the same tasks. Access to the database, and to its accompanying custom-built search software, is available electronically over the JANET system by contacting liz@psy.glasgow.ac.uk, from whom further information about the database and a user's guide to the database can be obtained. PMID- 1429957 TI - The natural history and treatment of child and adolescent affective disorders. PMID- 1429958 TI - Sleep studies in children with a mental handicap. PMID- 1429959 TI - A comparison of twins and singletons with child psychiatric disorders: an Item Sheet study. AB - An important assumption underlying the twin method of comparing MZ and DZ twins is that results from twin samples can be generalized to the larger singleton population. This study uses Item Sheet data on child psychiatric patients to compare twins and singletons on demographic, diagnostic and symptomatic variables. Although little difference was found between the two groups, conduct disorders were significantly over-represented in the twin population. The significance of this finding is discussed. This study lends overall support for the use of the twin method in child psychiatric samples. PMID- 1429960 TI - Behavioural and cognitive characteristics of conduct disordered-hyperactive boys from age 6 to 11: a multiple informant perspective. AB - Three subgroups of kindergarten boys (stable conduct disordered-hyperactive (SCDH), stable conduct disordered (SCD), stable non-deviant control (SC)) were defined and followed up three, four and five years later in primary school. Using assessments from multiple informants (teachers, mothers, peers, self), the results showed that SCDH boys were more hyperactive (i.e. overactive/inattentive) and displayed a greater diversity of conduct problems in school and home at follow-up compared to the other groups. These results and the fact that during early adolescence SCDH boys tend to develop a worse prognosis than SCD boys suggest that they should be distinguished. PMID- 1429961 TI - A motor presetting study in hyperactive, learning disabled and control children. AB - Motor presetting was investigated in hyperactive children, learning disabled children and normal controls. The reaction time of the hyperactive group was more sensitive to increases in interstimulus interval (event rate) than was that of the learning disabled and the controls. This finding indicates that hyperactive children have difficulty with motor presetting. PMID- 1429962 TI - Observations of hyperactive behaviour during vigilance. AB - A sustained attention deficit implies a deficit originating in the course of a task. A series of studies previously indicated that task inefficiency in hyperactive children is independent of task duration. The present study shows that differences in body activity between hyperactive and control children are also independent of task duration. However, the groups did differ in visual behaviour, i.e. hyperactive children did look away from the task more frequently as time proceeds. This visual behaviour did not interfere with task accuracy. It is argued that the results indicate that hyperactive children may have prevented a further deterioration of task efficiency over time through self stimulation. PMID- 1429963 TI - The performance of hyperactive and control preschoolers on a new computerized measure of visual vigilance: the Preschool Vigilance Task. AB - This study examines the ability of a new visual vigilance task, the Preschool Vigilance Task (PVT), to differentiate between hyperactive and control preschoolers. The PVT was designed to be an objective measure of attention specifically for use with the preschool-age population. Hyperactive and control preschoolers were tested on the PVT and the Continuous Performance Task (CPT). Results indicated that both were useful in differentiating between hyperactive and control preschoolers. Implications for the utility of the PVT and future research directions are discussed. PMID- 1429964 TI - School-age children's perceptions of coping with distress: strategies for emotion regulation and the moderation of adjustment. AB - An inventory was developed to assess children's perceptions of what they did to feel better in stressful situations, and to examine the role of these perceptions in moderating the relationship between stress and outcome. A total of 345 6-12 year old children from diverse backgrounds were interviewed. Children's perceptions of what they do to relieve distress could be organized into six factors including the use of social support, distraction/avoidance, and other categories of coping which show continuity with those identified for infants and toddlers. Several types of coping served as compensatory moderators of the relationship between stress and self-worth. PMID- 1429965 TI - Formal thought disorder in pediatric complex partial seizure disorder. AB - We compared the formal thought disorder ratings of 27 children with complex partial seizure disorder, 31 schizophrenic children and 58 normal children. The epileptic children with fullscale IQ scores below 100 had significantly more formal thought disorder than normal children with a similar IQ. The severity of their formal thought disorder was related to the age of seizure onset, seizure control and a diagnosis of schizophrenia spectrum disorder. The schizophrenic children had thought disorder irrespective of IQ scores. The cognitive correlates of their formal thought disorder scores differed from those of the epileptic children. Possible anatomical substrates of thought disorder in childhood complex partial seizure disorder and schizophrenia are discussed. PMID- 1429966 TI - Stable isotope dilution mass spectrometry for the simultaneous determination of cortisol, cortisone, prednisolone and prednisone in plasma. AB - A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of cortisol, cortisone, prednisolone and prednisone in human plasma is described. [1,1,19,19,19-2H5]Cortisol, [1,1,19,19,19-2H5]cortisone, [1,19,19,19-2H4]prednisolone and [1,19,19,19-2H4]prednisone were used as internal standards. Formation of the bismethylenedioxy-3-heptafluoro-n-butyryl (BMD-HFB) derivatives made possible the separation of the four corticosteroids with good gas chromatographic behaviour. The new double derivatization has been demonstrated to be of value for sensitive and selective quantification by this technique. Detection was performed by monitoring the molecular ion (M+) of the BMD-HFB derivatives for cortisone and prednisolone, the [M - 18]+ ion for cortisol, and the [M - 30]+ ion for prednisone. The method requires no complex corrections for contributions and provides good accuracy and precision. PMID- 1429967 TI - Chemiluminescence high-performance liquid chromatography for the determination of hyaluronic acid, chondroitin sulphate and dermatan sulphate. AB - A sensitive chemiluminescence high-performance liquid chromatographic method has been developed for the determination of hyaluronic acid, chondroitin sulphate and dermatan sulphate as their unsaturated disaccharide-dansylhydrazine derivatives involving an effective sample clean-up system. The dansylhydrazones of the unsaturated disaccharides derived from the hyaluronic acid, chondroitin sulphate and dermatan sulphate by chondroitinase ABC and/or chondroitinase ACII, were separated by reversed-phase chromatography using a mixture of 0.1 M sodium acetate buffer (pH 6.0) and 80% acetonitrile on a column (250 mm x 4.0 mm I.D.) packed with amide-80 silica beads (5 microns diameter). For post-column elution in the chemiluminescence system, 1 mM bis[2-(3,6,9-trioxadecanyloxycarbonyl)-4 nitrophenyl]oxalate and 3mM hydrogen peroxide in acetonitrile were used. The detection limit of each glycosaminoglycan was 100 fmol. The method was applicable to the determination of the levels of hyaluronic acid, chondroitin sulphate and dermatan sulphate in rat peritoneal mast cells. PMID- 1429968 TI - Determination of sialic acids in human serum by reversed-phase liquid chromatography with fluorimetric detection. AB - A simple, rapid and highly sensitive reversed-phase liquid chromatographic method has been developed for the determination of sialic acids in human serum. The sialic acids, released by hydrolysis of serum, are converted in borate buffer with malononitrile to highly fluorescent compounds. The reaction mixture is separated isocratically within 5 min using an octadecyl-bonded silica column and a mobile phase of methanol and ammonium acetate buffer (15:85, v/v; pH 5.5). Measurement of the fluorescence intensity of the reaction mixture at 434 nm with irradiation at 357 nm allowed determination of 30-1000 ng/ml of sialic acids with high reproducibility. The limit of detection was 2 ng/ml. Intra-day and inter-day coefficients of variation for assaying 300 ng/ml N-acetylneuraminic acid (NANA) were 1.5% (n = 9) and 2.6% (n = 7), respectively. The recoveries of NANA were 98.5-101.1% for serum. The method has been used for clinical determinations. PMID- 1429969 TI - Measurement of free amino acid levels in ultrafiltrates of blood plasma by high performance liquid chromatography with automatic pre-column derivatization. AB - Although there are many techniques available for the analysis of amino acids, deproteinization is still one of the major problems in the analysis of amino acids in physiological fluids. The method used to prepare the plasma and to remove the plasma protein has a marked effect on the final results. The most widely used method of deproteinization is precipitation with 5-sulphosalicyclic acid followed by centrifugation to remove the precipitated protein. We have not had success in using this deproteinization agent for the analysis of plasma amino acids by a high-performance liquid chromatographic method with automatic pre column o-phthaldialdehyde-3-mercaptopropionic acid and 9-fluorenylmethyl chloroformate derivatization because of the adverse effect of the sulphosalicyclic acid supernatant on the quantitation and separation. Ultrafiltration was used as an alternative method for the preparation of plasma samples in this experiment. The results were satisfactory for the analysis of plasma amino acids in 1500 samples during a period of four years. Some factors that might influence the results of the ultrafiltration were investigated. PMID- 1429971 TI - Improved gas chromatographic assay for the simultaneous determination of nitroglycerin and its mono- and dinitrate metabolites. AB - A sensitive, specific capillary gas chromatographic-electron-capture detection method for the simultaneous determination of nitroglycerin (GTN), 1,2- and 1,3 glyceryl dinitrate (1,2-GDN and 1,3-GDN, respectively) and 1- and 2-glyceryl mononitrate (1-GMN and 2-GMN, respectively) is reported. The minimum quantifiable concentration for GTN, GDNs and GMNs is 0.4 ng/ml in plasma, with extraction recoveries for GMNs greater than 76% and for GTN and the GDNs greater than 95%. Over the full range of quantifiable concentrations the inter-run assay precision and accuracy were less than 13 and 11%, respectively, for all five nitrates. Similar intra-run assay precision and accuracy values were found. The method was employed in the preliminary in vitro examination of GTN, GDN and GMN kinetics in human blood. Following addition of GTN to human blood, the ratio of 1,2-GDN to 1.3-GDN maximum concentrations (Cmax) was ca. 7:1, reflecting preferential denitration of the GTN molecule at the primary positions, while the Cmax ratio for 2-GMN to 1-GMN in this system was ca. 6:1, representing a highly selective if not specific primary denitration of the 1,2-GDN molecule. Following the intravenous administration of 1,2-GDN to five healthy male volunteers, 2-GMN/1 GMN Cmax ratios averaged 8.8:1, representing a highly selective but not specific formation of 2-GMN from the 1,2-GDN molecule. The assay will find utility in in vitro studies attempting to address the molecular pharmacology of GTN and its metabolites, and in in vivo clinical pharmacology studies attempting to address the relationship between pharmacokinetics and pharmacodynamics of GTN and its metabolites. PMID- 1429970 TI - Characterization of thyroxine-albumin binding using high-performance affinity chromatography. I. Interactions at the warfarin and indole sites of albumin. AB - A high-performance affinity column containing immobilized human serum albumin (HSA) was used to study the binding of thyroxine at the warfarin and indole sites of HSA. Frontal analysis, using R-warfarin and L-tryptophan as probes for these sites, demonstrated that the immobilized HSA had binding behavior equivalent to that observed for HSA in solution. By injecting R-warfarin or L-tryptophan in the presence of excess thyroxine, it was found that thyroxine was binding directly to both types of site. The warfarin and indole sites had relatively strong binding for thyroxine, with association constants at 37 degrees C of 1.4 x 10(5) and 5.7 x 10(5) M-1, respectively. The value of delta G for these sites ranged from -7 to -8 kcal/mol and had a significant entropy component. The techniques used in this study are not limited to thyroxine-HSA interactions, but should also be valuable in examining the site-specific binding of other drugs and hormones to HSA. PMID- 1429972 TI - Chiral separation of barbiturates and hydantoins by reversed-phase high performance liquid chromatography using a 25 or 50 mm short ODS cartridge column via beta-cyclodextrin inclusion complexes. AB - A high-performance liquid chromatographic method on a 25 or 50 mm short ODS cartridge column has been developed for the resolution of the enantiomers of some optically active barbiturates and hydantoins in human serum. beta-Cyclodextrin was used in the mobile phase. This method also seems to be an easy and effective way to test whether beta-cyclodextrin would be a useful chiral discriminator for a particular racemate. PMID- 1429973 TI - High-performance liquid chromatographic analysis of amphotericin B in plasma, blood, urine and tissues for pharmacokinetic and tissue distribution studies. AB - A sensitive and reproducible high-performance liquid chromatographic method was developed to assay ampherotericin B in plasma, blood, urine and various tissue samples. Amphotericin B was isolated from each sample matrix by solid-phase extraction (Bond-Elut). The eluate from Bond-Elut containing amphotericin B was injected onto a reversed-phase C18 column (Waters, mu Bondpak, 10 microns, 300 mm x 3.9 mm I.D.) with a mobile phase of 45% acetonitrile in 2.5 mM Na2EDTA at 1 ml/min. Detection of amphotericin B was by ultraviolet absorption at 382 nm. Blood and tissues were homogenized and extracted with methanol prior to Bond-Elut extraction. The extraction efficiencies of amphotericin B from plasma, blood and tissues were approximately 90, 70 and 75%, respectively. The sensitivity of the assay was less than or equal to 5 ng/ml for plasma, less than or equal to 25 ng/ml for blood, 2.5 ng/ml for urine and 50 ng/g for tissues. The linearity of the assay method was up to 2.5 micrograms/ml for plasma, 5 micrograms/ml for blood, 500 ng/ml for urine and 500 micrograms/g for tissues. The assay was reproducible with an intra-day coefficient of variation (C.V., n = 3) of less than 5% in general for plasma, blood and tissues. The inter-day C.V. of the assay was less than 5% for plasma (n = 5), less than 10% for blood (n = 4) and less than 5% for tissues (n = 3). The overall variability in the urine assay was generally less than 10%. This method has demonstrated significant improvement in the sensitivity and reproducibility in assaying amphotericin B in plasma and especially in blood, urine and tissues. We have employed this assay to compare the pharmacokinetic and tissue distribution profiles of amphotericin B in rats and dogs following administration of Fungizone and ABCD (amphotericin B cholesteryl sulfate colloidal dispersion), a lipid-based dosage form. In addition, the assay method for plasma and urine samples can also be applied to pharmacokinetics studies of amphotericin B in man. PMID- 1429974 TI - High-performance liquid chromatographic assay for amiodarone N-deethylation in microsomes of rat liver. AB - A reversed-phase high-performance liquid chromatographic assay using ultraviolet detection is described for determining the production of the major N-dealkylated metabolite of amiodarone in rat liver microsomes. The principal advantages of this method are its simple sample preparation (protein precipitation by acetonitrile), low detection limit for N-desethylamiodarone (0.05 mumol/l) and relatively short analysis time (16 min). Its analytical applicability is demonstrated by the comparison of the kinetic parameters (maximum velocity and Michaelis-Menten constant) between Sprague-Dawley and Dark-Agouti rats. PMID- 1429975 TI - Determination of the pyridinium metabolite derived from haloperidol in brain tissue, plasma and urine by high-performance liquid chromatography with fluorescence detection. AB - A sensitive and selective method for the determination of the pyridinium metabolite (HPP+) derived from the antipsychotic drug haloperidol (HP) in brain tissue, plasma and urine using high-performance liquid chromatography with fluorescence detection is described. The HPP+ present in biological samples was extracted using a Sep-Pak C18 cartridge. Recoveries of HPP+ ranged from 78 to 90%. Final separation and quantitative estimations of HPP+ were achieved on a C18 reversed-phase column employing a mobile phase of acetonitrile-30 mM ammonium acetate (40:60, v/v) containing 10 mM triethylamine and adjusted to pH 3 with trifluoroacetic acid. The fluorescence detection utilized an excitation wavelength of 304 nm and an emission wavelength of 374 nm. Standard curves were linear in the range of 2.5-100 ng/ml for brain tissue homogenate and plasma samples and 10-500 ng/ml for urine samples. The detection limit of HPP+ was about 1 ng/ml in all biological samples. The concentrations of HPP+ in brain tissue, plasma and urine from HP-treated rats were determined using this method. PMID- 1429976 TI - On-line solid-phase extraction and high-performance liquid chromatographic determination of nortriptyline and amitriptyline in serum. AB - An isocratic reversed-phase high-performance liquid chromatographic method with on-line solid-phase extraction for the simultaneous determination of amitriptyline and nortriptyline in serum has been developed. A 250-microliters serum sample is injected directly onto a commercially available CN cartridge and, after a washing step, the retained solutes are backflushed onto a bonded-phase CN column using a column-switching technique and a mobile phase composed of acetonitrile (26%) and 0.05 M phosphate buffer with diethylamine. Serum is diluted with 0.1 M sodium lauryl sulphate and centrifuged before the injection. Detection at 210 nm ensures sufficient sensitivity. The recovery is almost quantitative and the relative standard deviation ranges from 2.8 to 8.0% for concentrations of 200-40 ng/ml. Being rapid and simple, the method is convenient for routine use. PMID- 1429977 TI - Simultaneous determination of omeprazole and its metabolites in plasma and urine by reversed-phase high-performance liquid chromatography with an alkaline resistant polymer-coated C18 column. AB - Omeprazole (OPZ) is a proton pump inhibitor in gastric parietal cells. A reversed phase high-performance liquid chromatographic method was developed that enables concentrations of OPZ and its major metabolites, omeprazole sulphone (OPZ-SFN) and hydroxy-omeprazole (H-OPZ), to be determined simultaneously in plasma and that of H-OPZ in urine. To prevent decomposition of OPZ, all the processes (extraction, injection and elution) were carried out under alkaline conditions. Recoveries of the analytes and internal standard were greater than 93.1%. The intra- and inter-assay coefficients of variation were less than 9.1 and 6.4% for plasma samples and less than 2.9 and 3.9% for urine samples, respectively. The minimum determinable concentration (relative standard deviation 10-15%) was 10 ng/ml for all analytes in plasma and H-OPZ in urine samples. The clinical applicability of this assay method was evaluated by determining plasma concentration-and urinary excretion-time courses of the respective analyte(s) in four healthy volunteers after an oral dose of 20 mg of OPZ. The present assay is considered to be simple, precise and accurate and suitable for the study of the kinetic disposition and metabolism of OPZ, which is an extensively metabolized drug in the human liver. PMID- 1429978 TI - High-performance liquid chromatographic determination of N-[2(S)-(mercaptomethyl) 3-(2-methylphenyl)-1-oxopropyl]-L-methionine, the active plasma metabolite of a prodrug atriopeptidase inhibitor (SCH 42495), using a thiol selective (Au/Hg) amperometric detector. AB - A high-performance liquid chromatographic assay for the determination of N-[2(S) (mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methionine (SCH 42354; II), the active metabolite of the atriopeptidase inhibitor prodrug, N-[2(S) (acetylthiomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methi onine ethyl ester (SCH 42495; I), in human plasma was validated for use in clinical pharmacokinetic studies. Plasma (200 microliters) was processed by protein precipitation with acetone containing the internal standard, N-[2(S)-(mercaptomethyl)-3-(2 methylphenyl)-1-oxopropyl]-L- ethionine (III). Compound II was recovered (ca. 90%) in the supernatant after centrifugation and prepared for injection by the addition of 0.15 M monochloroacetic acid containing 0.2 mM EDTA. Separation of II and III was accomplished on commercially available reversed-phase C8 columns designed for the separation of basic compounds. Both compounds were detected using amperometric detection (+0.125 V versus Ag/AgCl) on a thin-layer Au/Hg amalgam electrode. The lower limit of quantitation was 10 ng/ml, where the inter assay precision (coefficient of variation) was +/- 11.4% and the inter-assay accuracy (bias) was +1.0%. No endogenous interferences were observed in the extracts obtained from drug-free plasma. The detector response (using either peak area or height ratios of II to III) was linear from 0.01 to 1.0 micrograms/ml. Compound II was stable in plasma supplemented with EDTA and sodium hydrogensulfite for at least 3 months when stored frozen at -78 degrees C; no significant decomposition of II was observed following three freeze-thaw cycles. The feasibility of this liquid chromatographic assay with electrochemical detection was demonstrated with plasma samples from hypertensive subjects administered 100 mg of compound I. PMID- 1429979 TI - Determination of cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in the urine of a patient with cystathioninuria using column liquid chromatography-mass spectrometry. AB - A method for the measurement of cystathionine and perhydro-1,4-thiazepine-3,5 dicarboxylic acid in the urine of a patient with cystathioninuria has been developed, using column liquid chromatography-mass spectrometry. Cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid were determined by scanning the [M + H]+ ions of each compound. The recoveries were 80-92.4% for cystathionine and 80-100% for perhydro-1,4-thiazepine-3,5-dicarboxylic acid after ion-exchange treatment. The results agreed well with those obtained using an amino acid analyser. The concentrations found for cystathionine and perhydro-1,4-thiazepine 3,5-dicarboxylic acid were 1.289 +/- 0.099 mg/ml and 0.310 +/- 0.0067 mg/ml, respectively. PMID- 1429980 TI - High-performance liquid chromatographic microassay for methyl ethyl ketone in urine as the 2,4-dinitrophenyl-hydrazone derivative. AB - We report a high-performance liquid chromatographic procedure for determining methyl ethyl ketone in urine. The method is based on pre-column derivatization with 2,4-dinitrophenylhydrazine and liquid-liquid extraction of the derivative. The analyte is chromatographically separated from other urine constituents in less than 12 min and is detected by UV absorption at 360 nm. Peak height and concentration are linearly related. The relative standard deviation assessed for within-day imprecision was 3.2% at the 2.21 mg/l level. The mean analytical recovery from urines spiked with 1.0 mg/l ketone was 96.0 +/- 6.1%. The simple sample handling, the small volume of urine required and the short amount of time taken for the whole procedure make it suitable for routine biomonitoring of exposure to methyl ethyl ketone in industrial workers. The concentration in urine from nine non-exposed controls was less than 0.1 mg/l. The concentrations measured in urine samples from 60 exposed workers ranged from 0.1 to 1.1 mg/l and from 0.3 to 3.6 mg/l at the before- and the end-shift collections, respectively. PMID- 1429982 TI - Determination of urinary 5-hydroxytryptophol by high-performance liquid chromatography with electrochemical detection. AB - A high-performance liquid chromatographic method for the routine determination of elevated urinary levels of the serotonin metabolite 5-hydroxytryptophol (5-HTOL) is described. Urine samples were treated with beta-glucuronidase, and 5-HTOL was isolated by solid-phase extraction on a small Sephadex G-10 column prior to injection onto an isocratically eluted C18 reversed-phase column. Detection of 5 HTOL was performed electrochemically at +0.60 V vs. Ag/AgCl. The limit of detection was ca. 0.05 microM, and the intra-assay coefficients of variation were below 6% with urine samples containing 0.2 and 2.1 microM 5-HTOL and a standard solution of 2.0 microM (n = 5). The recovery of 5-HTOL after the sample clean-up procedure was close to 100%. A good correlation (r2 = 0.97; n = 12) was obtained between the present method and a sensitive and specific gas chromatographic-mass spectrometric method. The total (free plus conjugated) 5-HTOL levels in urine were normally below 0.2 microM, but after an acute dose of alcohol they increased to 0.5-15 microM. PMID- 1429981 TI - Determination of cholesterol in sub-nanomolar quantities in biological fluids by high-performance liquid chromatography. AB - A highly sensitive method for the determination of cholesterol in biological fluids is described. Unsaponifiable lipids from rat serum and thoracic duct lymph chylomicron samples were treated with cholesterol oxidase. The product of the enzymatic reaction, delta 4-cholestenone, was analysed by normal-phase high performance liquid chromatography (HPLC) using hexane-isopropanol (95:5, v/v) as a mobile phase and detected with a UV spectrophotometer at 240 nm. When the standard samples containing varying amounts of cholesterol (0.15-3 nmol) were treated with cholesterol oxidase and analysed by HPLC (injected amounts 0.09-1.8 nmol of cholesterol), the peak areas increased proportionally with the amounts of authentic cholesterol with a correlation coefficient of 0.996. The values in these biological fluids determined by the HPLC method were identical to those obtained by enzymatic-colorimetric or gas chromatographic methods. Moreover, the detection limit (0.09 nmol) of the present method (0.15 nmol are required for the sample preparation) is lower than those of conventional methods (approximately 30 nmol). Because of the excellent sensitivity and reproducibility, this method is well suited for the determination of cholesterol in biological fluids where cholesterol concentration is low. PMID- 1429983 TI - High-performance liquid chromatographic separation of human apolactoferrin and monoferric and diferric lactoferrins. AB - A simple chromatographic separation of the different molecular forms of human milk lactoferrin according to their iron contents is described. The appropriate conditions were developed with a Mono-S cation-exchange column linked to an automated Urtrochrom GTi system. The pure lactoferrin with different iron binding (apolactoferrin, monoferric lactoferrin and diferric lactoferrin) separated into three peaks. The three peaks were eluted from the Mono-S column with 0.88, 0.97 and 1.05 M sodium chloride in 10 mM phosphate buffer (pH 7.0). PMID- 1429984 TI - Determination of 4,4'-methylenedianiline in hydrolysed human urine by micro liquid chromatography with ultraviolet detection. AB - 4,4'-Methylenedianiline was determined in human urine by micro liquid chromatography with ultraviolet detection. The combination of a thorough work-up and the high mass sensitivity of micro liquid chromatography gave the method very high sensitivity. Derivatization with pentafluoropropionic anhydride enhanced the resolution of the 4,4'-dimethylenedianiline peak. The detection limit, defined as blank plus three times the standard deviation of the blank, was 2 nmol/l of urine, for 10-microliters injection volumes. The detection limit, defined as three times the noise, was about ten times better. The within- and between-assay coefficients of variation were 4 and 6%, respectively, for samples containing 40 nmol/l. The method was applied for the monitoring of excreted 4,4' methylenedianiline in urine, during epicutaneous skin hypersensitivity testing (patch testing). PMID- 1429985 TI - Determination of trimethoprim and its oxidative metabolites in cell culture media and microsomal incubation mixtures by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method is presented for the determination of trimethoprim (TMP), 3'-hydroxy-TMP, 4'-hydroxy-TMP, alpha hydroxy-TMP and two TMP N-oxides. The last two metabolites appear to decompose on liquid extraction. TMP and its oxidative metabolites are separated using a C18 radial-compression column and quantified by UV detection at 230 nm. Calibration curves are linear from 0.5 to at least 50 microM. The limit of detection is 0.05 0.15 micrograms/ml. In in vitro rat liver metabolism studies. 3'- and 4' hydroxylation of TMP appear to be important metabolic pathways whereas TMP N oxides are minor metabolites. PMID- 1429986 TI - Stereospecific high-performance liquid chromatographic assay of metoprolol. AB - A valid, sensitive high-performance liquid chromatographic technique is reported for the separation of the two enantiomers of metoprolol in human plasma. The procedure involves pre-column derivatization with the homochiral reagent S-(+)-1 (1-naphthyl)ethyl isocyanate. Once formed, the diastereomers are separated using normal-phase high-performance liquid chromatography. Fluorescence detection (220 nm excitation; no emission filter) was utilized, resulting in baseline resolution (Rs greater than 1.5). The peaks corresponding to metoprolol enantiomers were free from interference throughout the examined range of 5-500 ng/ml; accuracy and precision were within approximately 10%. Analysis of a plasma sample collected from a healthy volunteer demonstrated that the assay is applicable to clinical studies. PMID- 1429987 TI - Improved high-performance liquid chromatographic assay for the stereoselective determination of mexiletine in plasma. AB - A simple and sensitive high-performance liquid chromatographic procedure for resolution of mexiletine enantiomers has been developed. Proteins from plasma samples containing RS-mexiletine were precipitated with a mixture of barium hydroxide and zinc sulphate before extraction under alkaline conditions with diethyl ether. Organic extracts were evaporated to dryness, and the residues reconstituted with 0.03 M hydrochloric acid (20 microliters). Derivatization with o-phthalaldehyde N-acetyl-L-cysteine reagent was performed after alkalinization with 0.1 M sodium borate. An aliquot of the resulting solution was injected onto a reversed-phase C18 column and resolution of mexiletine diastereoisomeric derivatives was achieved with a mobile phase consisting of methanol-50 mM sodium acetate (65:35), at a flow-rate of 1 ml/min. The retention times of S-(+)- and R (-)-mexiletine diastereoisomeric peaks were 14 and 15 min, respectively. Product elution was monitored by fluorescence detection using excitation and emission wavelengths fixed at 350 and 445 nm, respectively. Calibration curves were linear over the concentration range 2.5-500 ng/ml for each enantiomer (r greater than 0.99). The assay is shown to be suitable for pharmacokinetic studies after administration of a single oral dose of 200 mg of RS-mexiletine hydrochloride to healthy volunteers. PMID- 1429988 TI - Quantification of a decapeptide anticoagulant in rat and monkey plasma by high performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatographic method was developed to quantify a decapeptide anticoagulant in rat and monkey plasma. The compound and internal standard, a nonapeptide analogue, were extracted from plasma with an amino solid-phase extraction column with an extraction efficiency in the range 75 90%. A C18 analytical column was used to separate the analytes by gradient elution followed by ultraviolet detection at 215 nm. Quantification of the decapeptide over the concentration range 0.1-10.1 micrograms/ml resulted in an assay relative error and relative standard deviation both less than 10%. The anticoagulant decapeptide was stable in both rat and monkey plasma frozen at -20 degrees C. PMID- 1429989 TI - Determination of active 5-(N,N-hexamethylene)amiloride in pig plasma. AB - A simple, cheap and specific quantitative method for the determination of the selective Na+/H+ exchange inhibitor, 5-(N,N-hexamethylene)amiloride, in plasma and aqueous solutions has been developed. The method involves extraction with ethyl acetate, thin-layer chromatography and spectrofluorodensitometry. The compound was separated from several unidentified metabolites in plasma. The detection limit was 6 x 10(-7) M. The calculated metabolic extraction by the liver was 29%, and the plasma half-life was 12.8 min. The free, active concentration of 5-(N,N-hexamethylene)amiloride was 19.4% of the total concentration, as determined by equilibrium dialysis. PMID- 1429990 TI - Quantitative analysis of inositol lipids and inositol phosphates in synaptosomes and microvessels by column chromatography: comparison of the mass analysis and the radiolabelling methods. AB - Chromatographic methods that measure both the mass and the radiolabelling of various inositol lipids and inositol phosphates in tissues have been developed. The mass of phosphatidylinositol (PtdIns), phosphatidylinositol-4-monophosphate [PtdIns(4)P] and phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] was quantitated by measuring the inorganic phosphate, whereas inositol monophosphate (IP), inositol bisphosphate (IP2), inositol trisphosphate (IP3) and inositol tetrakisphosphate (IP4) were quantitated by using an enzymic method. The radiolabelling of various inositol lipids and inositol phosphates was determined by incubating the tissue samples with [3H]myo-inositol, separating individual inositol lipids and inositol phosphates, and measuring the radioactivity in each compound. Although the mass analysis method was sensitive enough to measure low levels of inositol lipids or inositol phosphates, the method was laborious and time-consuming. Compared with the enzymic method, the radiolabelling method was simple and fast, but it gave variable results. This study demonstrated differences in inositol lipid and inositol phosphate levels by radiolabelling and mass measurements, and agonist-stimulated phosphatidylinositol turnover of synaptosomes versus the blood-brain barrier as represented by microvessels. Although the mass of PtdIns, PtdIns(4)P and PtdIns(4,5)P2 was comparable in synaptosomes and microvessels, the incorporation of [3H]myo-inositol into phosphorylated PtdIns in microvessels was less than that in synaptosomes. PMID- 1429991 TI - Solid-phase extraction for the high-performance liquid chromatographic determination of indomethacin, suxibuzone, phenylbutazone and oxyphenbutazone in plasma, avoiding degradation of compounds. AB - A solid-phase extraction method was validated for the simultaneous high performance liquid chromatographic determination of indomethacin, suxibuzone, phenylbutazone, oxyphenbutazone and their degradation products. Indomethacin was added as internal standard to plasma samples, which were then acidified with citrate buffer and passed through a phenyl cartridge. The drugs were eluted with hexane-diethyl ether (1:1, v/v), and the organic extract was taken to dryness. The residue was dissolved in methanol and chromatographed on a C18 column with ultraviolet detection at 240 nm. The elution was isocratic with a mobile phase of 0.02 M ammonium sulphate-acetonitrile (45:55, v/v), pH 3. For indomethacin, suxibuzone, phenylbutazone and oxyphenbutazone the limit of quantitation was 0.05 microgram/ml. The linearity was checked between 0.05 and 100 micrograms/ml (r = 0.999); within this range the recovery was higher than 90% and the accuracy showed relative errors of less than 7.5%. The main advantage of this method is the avoidance of degradation by using citrate buffer instead of the usual 5 M hydrochloric acid to acidify the plasma. The method is also more specific and less time-consuming than the previously reported liquid-liquid extraction, and could possibly be automated. PMID- 1429992 TI - Liquid chromatography of the potential memory-enhancing agent CL 275,838 and its main metabolites, using a post-column photochemical reactor and fluorimetric detection. AB - On irradiation with short-wavelength ultraviolet light, the potential memory enhancing compound CL 275,838 (I) and its desbenzyl derivative CL 286,527 (metabolite II) are cleaved into the highly fluorescent derivative CL 228,346 (metabolite IV). This reaction was exploited for the sensitive and selective detection of these compounds in human and animal plasma, after reversed-phase high-performance liquid chromatography on a Supelco LC18 DB column (15 cm x 4.6 mm I.D.) at room temperature. The parent compound and its metabolites were isolated from plasma constituents using the Sep-Pak C18 Plus cartridge, with satisfactory recovery (76-90%) and selectivity. The detection limits were ca. 1.25, 5 and 0.3 ng/ml for I, II and IV, respectively, using 1 ml of plasma. The validation procedure, which includes analysis of multiple ascending calibration curves based on between-day values and replicate analysis of quality control samples analysed with each standard curve, indicated acceptable precision and accuracy of the method within the concentration ranges investigated, the overall coefficient of variation and relative error being less than 10%. The method was successfully applied to plasma samples from healthy volunteers and animals after single of multiple doses of compound I. Metabolites II and IV were detectable in plasma of all species, the former at higher concentrations than the parent compound and metabolite IV. Together with the fact that metabolite II retains much of the parent compound's biological activity in vivo and in vitro, this suggests that it may contribute to the pharmacological effects of compound I. PMID- 1429993 TI - Assay of sialidase activity using ion-exchange chromatography and acidic ninhydrin reaction. AB - A new assay method for sialidase (EC 3.2.1.18) activity using ion-exchange chromatography and acidic ninhydrin reaction has been developed. Fetuin, 4 methylumbelliferyl-N-acetylneuraminic acid (MUB-NANA), gangliosides and N acetylneuramin-lactose were examined as substrates. Free sialic acid liberated from these substrates by sialidase reaction was isolated with a Dowex 1-X8 column (trifluoroacetate form, 1.5 cm x 0.5 cm I.D.) and determined by acidic ninhydrin reaction. Among the substrates tested, MUB-NANA was the best in the present method, N-Acetylneuramin-lactose could not be used as the substrate, because it was not separated from liberated sialic acid under the conditions used. The recovery of N-acetylneuraminic acid was above 88%, and the sensitivity of the method was 20 nmol in 300 microliters of the reaction mixture. The method was applied to the sialidase assay during its purification from rat skeletal muscle, and a Michaelis constant of 1.15 mM was obtained with MUB-NANA as the substrate. The method using the acidic ninhydrin reaction was simple and exhibited good reproducibility. PMID- 1429994 TI - Thin-layer chromatographic detection of zeranol and estradiol in fortified plasma and tissue extracts with Fast Corinth V. AB - In an attempt to improve sensitivity of thin-layer chromatographic (TLC) analysis and selectivity of visualizing agents for detection of estrogenic anabolic hormones, several dyes were screened for their chromogenic interactions with estrone, estradiol, diethylstilbestrol (DES), zeranol (zearalanol), zearalanone, and mycotoxins, zearalenone and zearalenol. Fast Corinth V salt was selected for its relatively high sensitivity. These anabolic compounds were separated by TLC and visualized with Corinth V and the results compared to iodine and starch visualization. Fortified bovine plasma and tissues (kidney, liver and muscle) and chicken muscles were analyzed after a clean-up procedure using solid-phase dual columns of alumina and anion-exchange resin. Iodine-starch clearly detected 4 ng of estradiol and DES while zeranol and zearalenone were detected at higher levels (10 ng). Fast Corinth V showed distinct spots with 2 ng of zeranol and 4 ng of zearalenone while faint spots were observed with estradiol and estrone standards. DES was not detectable at these levels. Less background interference was observed with Corinth V than with iodine-starch. The former confirmed spots detected by iodine-starch. This study suggests its selectivity for detection of zeranol and its metabolite, zearalanone, in the presence of steroidal compounds. PMID- 1429995 TI - Multidimensional high-performance liquid chromatography on Pinkerton ISRP and RP18 columns: direct serum injection to quantify creatinine. AB - A two-dimensional high-performance liquid chromatographic method for the determination of creatinine with direct serum injection without sample pretreatment has been developed. The column-switching technique allowed a switch from columns packed with internal surface reversed-phase (ISRP) material to columns of almost any other material, even if the eluents necessary in a particular case do not appear to be directly compatible. A Pinkerton ISRP column, which stands out because of its very good stability when loaded with undiluted serum samples, was used as precolumn. The creatinine-containing fraction was switched to a reversed-phase Shandon RP18 column and was focused there by alteration of the eluent from pH 6.5 to phosphoric acid-ion-pair reagent. The separation occurs via a pH gradient, with ultraviolet detection at 234 nm. This method stands out particularly for its good long-term stability, simple sample handling without pretreatment, high selectivity, a broad linearity (0.3-30 mg/dl creatinine), good reproducibility (inter-assay coefficient of variation less than 3%) and high recovery (97-100%) relative to values obtained with gas chromatography-mass spectrometry. PMID- 1429996 TI - Preparation of samples for high-performance liquid chromatography of inositol phosphates. AB - A simple method is described for the removal of extraneous material from tissue extracts prior to anion-exchange high-performance liquid chromatography of inositol phosphates. Samples are prepared by extraction with trichloroacetic acid or perchloric acid followed by removal of the excess acid. The extracts are then passed through small Dowex-50 cation-exchange columns and eluted with water. Dowex-50 pretreatment removes most of the ultraviolet absorbing material and cations from the samples but does not alter the content of inositol phosphates. This treatment results in improved reliability of chromatography, especially with respect to weakly retained molecules such as adenosine 5'-phosphate and the isomers of inositol monophosphate. In addition, sample pretreatment improves the useful lifetime of the analytical anion-exchange columns. PMID- 1429997 TI - One-dimensional thin-layer chromatographic separation of phospholipids and lysophospholipids from tissue lipid extracts. AB - A modified one-dimensional thin-layer chromatographic procedure is presented for the separation from tissues of five phospholipids (phosphatidylserine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylcholine and sphingomyelin) and three lysophospholipids (lysophosphatidylserine, lysophosphatidylethanolamine and lysophosphatidylcholine). This is achieved by simple involvement of 0.4% ammonium sulphate in silica gel H and of acetone in a developing solvent as chloroform-methanol-acetic acid-acetone-water (40:25:7:4:2, v/v). The procedure is simple and the separation is reproducible. The weakness of this method is the partial degradation of phosphatidylethanolamine to lysophosphatidylethanolamine, but a method to prevent this degradation is also presented. PMID- 1429998 TI - High-performance liquid chromatographic-mass spectrometric assay of busulfan in serum and cerebrospinal fluid. AB - A liquid chromatographic-mass spectrometric method has been developed to determine busulfan concentrations in the cerebrospinal fluid and serum of some children undergoing bone marrow autotransplantation. After two liquid-liquid extraction steps with dichloromethane on a biological matrix, the separation of busulfan was carried out by isocratic reversed-phase chromatography. The mass spectrometric system was operated in electron-impact mode. Principal ions at m/z 175, 111 and 79 were observed for busulfan, but only m/z 175 was chosen for the quantification of the analyte. The retention time of busulfan was 2.5 min. The detection limit of 100 ng/ml allowed the determination of cerebrospinal fluid and serum busulfan concentrations during the four days of high-dose (1 mg/kg) treatment prior to autotransplantation in five child patients. PMID- 1429999 TI - Determination of the R-(-) and S-(+) enantiomers of the monohydroxylated metabolite of oxcarbazepine in human plasma by enantioselective high-performance liquid chromatography. AB - An enantioselective liquid chromatographic assay for the simultaneous determination of the S-(+) and R-(-) enantiomers of the monohydroxylated metabolite of oxcarbazepine in human plasma is described. The metabolite is the active principle. The method is based on the extraction of plasma with diethyl ether-dichloromethane (2:1, v/v), separation of the organic phase, evaporation of the solvent and dissolution of the residue in the mobile phase. The two enantiomers were resolved on a Chiralcel OD (250 mm x 4.6 mm I.D.) high performance liquid chromatographic column. The separation was achieved by isocratic elution with n-hexane-2-propanol (77:23, v/v). The flow-rate of the mobile phase was 1.0 ml/min and the two enantiomers were detected by ultraviolet absorbance at 210 nm. The analytical method is suitable for the quantitative and simultaneous determination of the two enantiomers in plasma at concentrations down to 0.4 mumol/l after administration of oxcarbazepine. PMID- 1430001 TI - Measurement of halofantrine and its major metabolite desbutylhalofantrine in plasma and blood by high-performance liquid chromatography: a new methodology. AB - A new high-performance liquid chromatographic assay for the measurement of halofantrine and desbutylhalofantrine in plasma and whole blood is described. The method involves a smaller sample volume, simplified sample pre-treatment and a shorter run-time, and is adaptable to the measurement of samples dried onto filter paper strips. Using this method, which is both selective and sensitive, plasma concentration versus time profiles for both substances have been investigated following a single oral dose (500 mg) of halofantrine hydrochloride to a healthy adult volunteer. In addition, a clinical study designed to evaluate the disposition and elimination of the two compounds in children with non-severe falciparum malaria is in progress. PMID- 1430000 TI - Measurement of dothiepin and its major metabolites in plasma by high-performance liquid chromatography. AB - This paper describes a reversed-phase high-performance liquid chromatographic method which will simultaneously measure dothiepin and its three major metabolites (northiaden, northiaden-S-oxide and dothiepin-S-oxide) in plasma using trimipramine as internal standard. Sample preparation involved a basic extraction using diethyl ether followed by an acid back-extraction. The method we report is linear over the range 50-1000 ng/ml (r = 0.999), for all analytes. Total imprecision is less than 11% (coefficient of variation) and accuracy is greater than 94% (n = 20). Recovery of analytes varied considerably from 51.7% for northiaden-S-oxide to 90.2% for dothiepin-S-oxide. PMID- 1430002 TI - Determination of dextropropoxyphene and norpropoxyphene in plasma by high performance liquid chromatography. AB - A simple and sensitive procedure for the routine assay of the analgesic drug dextropropoxyphene and its main metabolite, norpropoxyphene, in plasma is described. After liquid-liquid extraction from alkalinized plasma and back extraction into a small volume of an acidic aqueous phase, the aqueous phase was injected into a column packed with 3-microns octadecylsilica particles. Ultraviolet absorbance detection at 210 nm was used. Concentrations down to 2 nM could be determined for both compounds; at this level, the intra-assay coefficient of variation was 5%. PMID- 1430003 TI - High-performance liquid chromatographic determination of angiotensin II receptor antagonists in human plasma and urine. I. DuP 532 (L-694,492). AB - A sensitive reversed-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the analysis of a new angiotensin II receptor antagonist, DuP 532 (L-694,492), in human plasma and urine. The analyte and internal standard are extracted from plasma and urine at a pH between 3.3 to 3.6 by liquid-liquid extraction and analyzed on a C6 column with ultraviolet detection at 254 nm. The mobile phase is composed of acetonitrile and phosphate buffer at pH 2.5. The limits of quantification are 6 and 7.5 ng/ml for plasma and urine, respectively. PMID- 1430004 TI - Affinity purification of proteinases by a combination of immobilized peptidyl aldehyde and semicarbazone. AB - D-Phe-Phe-argininal semicarbazone and Tyr-Gly-Gly-Phe-Leu-Arg-argininal semicarbazone were prepared using the solution phase synthesis method and characterized by mass spectrometry and nuclear magnetic resonance spectroscopy. The tripeptide and heptapeptide semicarbazones were individually immobilized on affi-Gel 15 resulting in two affinity columns called S3 and S7, respectively. A third affinity column was obtained by hydrolysing the semicarbazone moiety in column S3 to aldehyde (column A3). Serine proteinases such as trypsin or rat plasma kallikrein almost quantitatively bind to either S3 or A3 affinity columns. Under optimized conditions, more than 97% of trypsin bound to both columns S3 and A3. At a lower ionic strength and higher pH, 80-85% of rat plasma kallikrein bound to the same columns. Elution of both enzymes was achieved using mild conditions at near neutral pH and in the presence of a small amount of denaturant. Both proteinases were identified and characterized by high performance liquid chromatography, sodium dodecylsulphate polyacrylamide gel electrophoresis and by their substrate specificity and inhibition profiles. A single purification (six-to seven-fold) step using either column S3 or A3 allowed the preparation of pure trypsin from commercial sources. Starting from rat plasma partially purified by a phenyl boronate column, fractionation on the S3 column allowed approximately an 87-fold purification of rat plasma kallikrein. However, serial purification of rat plasma kallikrein on column S7 followed by column A3 resulted in a purification factor of about 455. PMID- 1430005 TI - Modified nucleosides in human serum. AB - Methylated purines and pyrimidines derived from the degradation of transfer ribonucleic acid have been shown to be excreted in abnormal amounts in the urine of patients with cancer. Recent technology developed by Gehrke and Kuo has allowed the separation and quantification of modified nucleosides in serum using reversed-phase high-performance liquid chromatography with diode-array measurement. Serum levels of ten modified nucleosides were measured in 37 normal healthy adults to establish normal values and to correlate activity with age and sex. In addition, serum levels of patients with several malignancies were measured to determine activity in these diseases. Levels of modified nucleosides in normal individuals were consistently reproducible and showed no significant variation among males versus females or with age. Patients with malignant diseases showed consistent elevations and these were highest in patients with more advanced disease. The evidence of no significant differences in the mean levels of modified nucleosides in serum with age or sex in normal adults and elevations in patients with malignancies demonstrate the potential value of modified nucleosides as cancer biomarkers. PMID- 1430006 TI - High-performance liquid chromatographic method for routine determination of vitamins A and E and beta-carotene in plasma. AB - A simple and reliable reversed-phase high-performance liquid chromatographic (HPLC) method for the routine determination of vitamins A and E and beta-carotene in plasma (or serum) with wavelength-programmed ultraviolet-visible absorbance detection is described. A 200-microliters aliquot of serum or plasma sample, after deproteinization with ethanol, and containing tocopherol acetate as internal standard, was extracted with butanol-ethyl acetate. Sodium sulphate was added for dehydration. Analytes of extracted samples were found to be stable for at least four days. A 10-microliters aliquot of this organic extract was used for HPLC analysis. The mobile phase was methanol-butanol-water (89.5:5:5.5, v/v) and the flow-rate was set at 1.5 ml/min. The analytes of interest were well separated from other plasma constituents within 22 min at 45 degrees C. The lowest detection limits of vitamins A and E and beta-carotene were 0.02, 0.5 and 0.1 microgram/ml, respectively. The recovery and reproducibility of the present method were around 90%. The method is sensitive, specific and can be used for epidemiological studies and for routine determination of vitamin deficiency. Several important factors that may affect the analysis are also discussed in this paper. PMID- 1430007 TI - Direct assay of glutathione peroxidase activity using high-performance capillary electrophoresis. AB - A fast, sensitive and direct method has been developed for the determination of glutathione peroxidase activity (both selenium- and non-selenium-dependent) in cell-free preparations. The assay is based on the separation and quantitation of reduced and oxidized glutathione by capillary electrophoresis. The electrophoretic separation buffer was 100 mM sodium tetraborate (pH 8.2) containing 100 mM sodium dodecylsulphate. A micellar electrokinetic mechanism took place under these conditions, and a total mass recovery was observed for both peptides. The reproducibility of migration times was excellent (less than 3% variability). A linear detector response range was observed in the range 5-50 U/ml, and both the reproducibility and accuracy were satisfied. Samples out of this linear range could be analysed by either increasing the reaction time or diluting the enzyme preparation. The results obtained with the new direct capillary electrophoresis assay were compared with those derived from a reversed phase high-performance liquid chromatographic and spectrophotometric coupled assay. A very good agreement was found between the two direct assay methods in all samples. Capillary electrophoresis is a versatile technique that allows the automation of the glutathione peroxidase assay in a reproducible manner and within a relatively short time with sufficient accuracy and precision. PMID- 1430008 TI - Diuretic screening in human urine by gas chromatography-mass spectrometry: use of a macroreticular acrylic copolymer for the efficient removal of the coextracted phase-transfer reagent after derivatization by direct extractive alkylation. AB - A simple and efficient procedure has been developed for the derivatization of diuretic agents in human urine by direct extractive alkylation and their detection by gas chromatography-mass spectrometry. The procedure is an improvement over previous extractive alkylation methods because of the development of a simple clean-up step using a macroreticular acrylic copolymer (SM-7 resin) to remove the coextracted phase-transfer reagent from the organic phase after derivatization. With 1 ml of sample the method gives detection limits in the range 10-50 ng/ml for acetazolamide, probenecid, dichlorphenamide, hydroflumethiazide, furosemide, chlorthalidone, bumetanide, hydrochlorothiazide, quinethazone, bendroflumethiazide, metolazone and cyclopenthiazide. PMID- 1430009 TI - Determination of three metabolites of a new angiotensin-converting enzyme inhibitor, imidapril, in plasma and urine by gas chromatography-mass spectrometry using multiple ion detection. AB - A specific and sensitive gas chromatographic-mass spectrometric method for the determination of three metabolites of the angiotensin-converting enzyme inhibitor, imidapril, in plasma and urine was developed. The metabolites were isolated from plasma and urine using a Bond Elut C18 solid-phase extraction cartridge. The isolated metabolites were converted to sensitive derivatives by pentafluorobenzyl bromide and heptafluoro-n-butyric acid anhydride. Following derivatization, the sample solutions were analysed by wide-bore column gas chromatography-mass spectrometry with multiple ion detection. The detection limits of the three metabolites were each 1 ng/ml in plasma and 5 ng/ml in urine. Analysis of the spiked plasma and urine samples demonstrated the good accuracy and precision of the method. This method was very useful for use in pharmacokinetic and bioavailability studies of the three metabolites of imidapril in humans. PMID- 1430010 TI - Analytical and semi-preparative high-performance liquid chromatographic separation and assay of hydroxychloroquine enantiomers. AB - (+/-)-Hydroxychloroquine (HCQ) is an antimalarial and anti-arthritic drug which is administered as the racemate. An accurate, precise and sensitive high performance liquid chromatographic assay was developed for the determination of HCQ enantiomers in samples from human plasma, serum, whole blood, and urine. After addition of (+/-)-chloroquine (internal standard), samples of blood component (0.5 ml) or urine (0.1 ml) were alkalinized and extracted with 5 ml of diethyl ether. After solvent evaporation the residues were derivatized with (+) di-O-acetyl-L-tartaric anhydride at 45 degrees C for 30 min. The resulting diastereomers were then resolved using a C8 analytical column with a mobile phase consisting of 0.05 M KH2PO4 (pH 3)-methanol-ethanol-triethylamine (78:22:1:0.08). The ultraviolet detection wavelength was set at 343 nm. The derivatized HCQ enantiomers eluted in less than 40 min, free of interfering peaks. Excellent linear relationships (r2 > 0.997) were obtained between the area ratios and the corresponding plasma concentrations over a range of 12.5-500 ng/ml. The diastereomers could be hydrolysed using microwave energy and neutral pH, which enabled us to resolve the enantiomers on a semi-preparative (C18 column) scale. The method was suitable for the analysis and semi-preparative separation of HCQ enantiomers. PMID- 1430011 TI - Determination of vinorelbine (Navelbine) in tumour cells by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method has been developed for the determination within tumour cells of a new vinca alkaloid, vinorelbine. Extractions of vinorelbine from cells were carried out using absolute ethanol. The extracts were injected into a reversed-phase system consisting of two Novapak C18 columns connected in series. The mobile phase was acetonitrile-phosphate buffer, pH 2.7 (60:40, v/v). Using a fluorescence detection, the limit of determination was 8 pmol injected. This method would be suitable for studying the cellular pharmacokinetics of vinorelbine in patients. PMID- 1430012 TI - Multiple peak formation from reversed-phase liquid chromatography of recombinant human platelet-derived growth factor. AB - Reversed-phase liquid chromatography of recombinant platelet-derived growth factor (PDGF) results in the appearance of at least four distinguishable peaks. The relative areas of these peaks are, in part, dependent upon the gradient time and the temperature. Isolation and reinjection of each peak gave chromatographic profiles comparable to that obtained from unfractionated PDGF. Increasing the temperature above 60 degrees C resulted in a single peak that, when isolated and reinjected at ambient temperature, produced a chromatogram comparable to PDGF which had not been exposed to elevated temperature. Sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that all four peaks had the same molecular mass as PDGF and were active as determined by a PDGF mitogenic bioassay. These results indicate that multiple conformations of PDGF are present and we postulate that their appearance may be a result of isomeric structures arising from the presence of Pro-Pro bonds within the primary structure of the protein. PMID- 1430013 TI - Determination of sterols, erythrodiol, uvaol and alkanols in olive oils using combined solid-phase extraction, high-performance liquid chromatographic and high resolution gas chromatographic techniques. AB - A method is described for the determination of the sterol, erythrodiol, uvaol and alkanol content in olive oils by means of solid-phase extraction and high performance liquid chromatography, instead of liquid-liquid and thin-layer chromatographic separations, the following step being high-resolution gas chromatographic separation. This type of procedure allows the simultaneous analysis of a larger number of samples and a substantial reduction in manual operations. Comparisons were made between the two methods on 100 different olive oils and with a statistical analysis of the results (Student's t-test). PMID- 1430014 TI - Determination of aminoglycoside antibiotics in pharmaceuticals by capillary zone electrophoresis with indirect UV detection coupled with micellar electrokinetic capillary chromatography. AB - Aminoglycoside antibiotics can be determined by capillary zone electrophoresis (CZE) with indirect UV detection in the anionic mode with a reversed electroosmotic flow (EOF) by addition of FC 135 to the background electrolyte. The effective mobilities of thirteen aminoglycoside antibiotics were determined as a function of pH. Applying CZE with indirect UV detection in the anionic mode and reversed EOF coupled with micellar electrokinetic capillary chromatography with the cationic surfactant cetyltrimethylammonium bromide, both neutral and charged antibiotics can be determined in combined pharmaceuticals. As an example, neomycin and hydrocortisone were determined in Otosporin eardrops. PMID- 1430015 TI - Determination of coenzyme Q by non-aqueous reversed- phase liquid chromatography. AB - A non-aqueous reversed-phase liquid chromatographic method for determination of coenzyme Q10 in pharmaceutical formulations has been developed. The reversed phase system provides better reproducibility and better selectivity for the separation of coenzyme Q10 analogues and degradation products than studied normal phase systems. Furthermore, the non-aqueous mobile phase showed a very good solubility and provides a greater variety of work-up solvents for the lipophilic formulations than aqueous mobile phases. Validation studies showed detector response linearity over a concentration range of 0.2-100 micrograms/ml. The lower limit of detection was 2 ng on-column. The intra-assay precision (relative standard deviation) for a soybean oil formulation was 2.0% (n = 11). PMID- 1430016 TI - Determination of ascorbic acid in elemental diet by high-performance liquid chromatography with electrochemical detection. AB - Determination of ascorbic acid in a multi-component elemental diet was performed by high-performance liquid chromatography with electrochemical detection. This method is suitable for the routine determination of ascorbic acid in elemental diet because it is simple, rapid, sensitive, highly selective and reproducible. The calibration graph of ascorbic acid was linear in the range 0-1.0 micrograms. The recovery of ascorbic acid was over 95% by the standard addition method. There was good agreement between the concentrations of ascorbic acid stated and found. PMID- 1430018 TI - Effect of total percent polyacrylamide in capillary gel electrophoresis for DNA sequencing of short fragments. A phenomenological model. AB - Polyacrylamide capillary gels were prepared with constant (5% C) cross-linker concentration and with total acrylamide concentration ranging from 2.5 to 6% T. At each acrylamide concentration, peak spacing was constant for DNA sequencing fragments ranging from 25 to 250 nucleotides in length. Peak spacing increased linearly with the total acrylamide concentration. The intercept of the retention time vs. fragment length plot was independent of % T. Ferguson plots were constructed for short DNA fragments; the polyacrylamide pore size falls in the 2.5 to 3.5 nm range for the gels studied. Theoretical plate count is independent of total acrylamide concentration; longitudinal diffusion, and not thermal gradients, limit the plate count. A phenomenological model is presented that predicts retention time, plate count, and resolution for sequencing fragments ranging in size from 25 to 250 bases and gels that range from 2.5 to 6% total acrylamide. PMID- 1430017 TI - Application of capillary isoelectric focusing with universal concentration gradient detector to the analysis of protein samples. AB - The design of a new capillary isoelectric focusing (cIEF) instrument, composed of a rugged cartridge holding a short piece of capillary and a universal, inexpensive concentration gradient detector, was optimized and applied to the analysis of various protein samples. High-efficiency cIEF separations with sub femtomole detection limits for absolute amounts were obtained using 10 microns I.D. capillaries with large O.D.-to-I.D. ratios. An electric field strength of 1 kV/cm applied in the focusing step resulted in a 10(-8) M on-column concentration detection limit, which corresponded to 10(2) amol absolute amount of proteins. The detection volume was estimated to be 2 pl, which is among the smallest values reported to date for any optical or spectroscopic detector. When a 6-cm long capillary was used, proteins with isoelectric points ranging from 4.7 to 8.8 could be analyzed in about 5 min, the shortest analysis time ever reported for cIEF. Compared with commercial cIEF instruments with UV-visible absorbance detectors, the instrument is easier to use and has lower detection limits and better resolution. Several protein mixtures and real samples were separated with this instrument. PMID- 1430019 TI - Influence of pH on the migration properties of oligonucleotides in capillary gel electrophoresis. AB - The effect of pH on the electrophoretic migration properties of single-stranded oligodeoxyribonucleotides in capillary gel electrophoresis was investigated. Different homooligodeoxyribonucleotides of equal chain length showed significant differences in relative migration when the pH of the gel buffer was varied from pH 6 to 8, parallel with the running buffer. A similar variation in migration order was observed during the electrophoretic equilibration of a pH 8 gel-filled capillary column with a pH 6 running buffer. In the latter instance, the current reached the new level after 20 min of electrophoretic equilibration with the pH 6 running buffer. However, it was observed that the migration order characteristic of the pH 6 gel was achieved only after 4 h of electrophoretic equilibration. To avoid this time-consuming equilibration process, these results suggest that gel filled capillary columns should be prepared with the same buffer (composition and pH) that will be used as the running buffer during the separations. PMID- 1430020 TI - Determination of vasoactive intestinal peptide in rat brain by high-performance capillary electrophoresis. AB - A high-performance capillary electrophoresis (HPCE) method for determining vasoactive intestinal peptide (VIP) in rat brain was developed. Cerebral cortex was first extracted by solid-phase extraction and purified by reversed-phase high performance liquid chromatography. The VIP-rich fraction was further analysed by capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography using a commercial HPCE instrument with UV detection. The identity of the peak of endogenous VIP was confirmed by performing multiple CZE analyses at different pH values. This HPCE method allows VIP to be detected and measured with good molecular specificity and could represent a reference method to validate data obtained by radioimmunoassay. PMID- 1430021 TI - Monitoring excitatory amino acid release in vivo by microdialysis with capillary electrophoresis-electrochemistry. AB - Capillary electrophoresis (CE) with electrochemical detection (ED) was used to determine extracellular levels of aspartate, glutamate and alanine in samples from the frontoparietal cortex of the rat which were obtained by microdialysis. The method was used to monitor the effect on the overflow of the excitatory amino acids aspartate and glutamate of an influx of high concentrations of potassium ion. Samples were derivatized with naphthalenedialdehyde-cyanide prior to analysis. Detection limits for aspartate and glutamate were 80 and 100 nM, respectively. CE-ED is extremely useful for the analysis of microdialysis samples because of the very small sample volumes required by this analytical technique. The use of ED provides the requisite sensitivity and allows verification of peak purity by voltammetry. PMID- 1430023 TI - Capillary electrophoretic determination of the protease Savinase in cultivation broth. AB - The highly basic washing enzyme Savinase and various analogues were analysed by micellar electrokinetic chromatography (MEKC) and electrophoresis. Broth samples were withdrawn during the cultivation of Savinase by recombinant microorganisms. Savinase peak areas obtained by MEKC-electrophoretic analysis were normalized with respect to migration time and compared with traditional enzyme activity measurements. The electropherograms indicated thermal degradation of the Savinase molecule at high field strengths. Baseline separation of Savinase and two analogues was achieved. PMID- 1430022 TI - Effect of buffer constituents on the determination of therapeutic proteins by capillary electrophoresis. AB - Capillary electrophoresis has proved to be a versatile method for the determination of proteins, peptides and amino acids in pharmaceutical formulations. For quantification of the capillary electrophoresis data, however, significant errors may result if the analysis is performed using improper separation conditions. The peak area response for protein analytes, which is generally low in conventional UV detection, may also vary dramatically depending on the nature of the buffer used in the separation. This paper describes the effects of various buffer constituents and analytical conditions on the capillary electrophoretic separation and quantification of a humanized monoclonal antibody in bulk form and in a typical therapeutic formulation. For optimum peak area response and reproducibility, protein derivatization with an appropriate chromophore (e.g., fluorescamine) and separation in the presence of a moderate ionic strength buffer containing lithium chloride, tetramethylammonium chloride or trimethylammonium propylsulfonate is recommended. General guidelines for the determination of proteins by capillary electrophoresis and a rationale for the use of internal standards to improve the quantification of data are also discussed. PMID- 1430024 TI - Separation of phosphorylated histone H1 variants by high-performance capillary electrophoresis. AB - High-performance capillary electrophoresis (HPCE) was used to separate successfully distinct phosphorylated derivatives of individual histone H1 variants. With an untreated capillary (50 cm x 75 microns I.D.) the electrophoresis was performed in about 15 min. Inconvenient interactions of these highly basic proteins with the capillary wall were eliminated by using 0.1 M sodium phosphate buffer (pH 2.0) containing 0.03% hydroxypropylmethylcellulose. Under these experimental conditions the histone H1 variants H1b and H1c obtained from mitotic enriched NIH 3T3 fibroblasts and isolated by reversed-phase high performance liquid chromatography were clearly separated in their non phosphorylated and different phosphorylated forms. This result was confirmed by acid-urea gel electrophoresis, comparison with non-phosphorylated histones H1b and H1c, isolated from quiescent NIH 3T3 cells, and incubation of multi phosphorylated histone H1b with alkaline phosphatase and subsequent acid-urea and capillary electrophoresis. The results illustrate that the application of HPCE to the analysis of histone modifications provides a new alternative to traditional gel electrophoresis. PMID- 1430025 TI - Ultramicro enzyme assays in a capillary electrophoretic system. AB - This paper describes an ultramicro method for achieving enzyme assays. Enzyme saturating concentrations of substrate, coenzyme when appropriate, and running buffer were mixed and used to fill a deactivated fused-silica capillary in a capillary zone electrophoresis apparatus. The enzyme glucose-6-phosphate dehydrogenase was injected by either electrophoresis or siphoning and mixed with the reagents in the capillary by electrophoretic mixing. Enzyme activity was assayed by electrophoresing the product, reduced nicotinamide adenine dinucleotide phosphate, to the detector where it was detected at 340 nm. Under constant potential, the transport velocity of enzyme and the product was generally different. This caused product to be separated from the enzyme after it was formed. Because product formation was much faster than the rate of enzyme product separation, product accumulated. The amount of accumulated product was inversely related to operating potential. In the extreme case, the operating potential was zero. Zero potential assays were generally carried out by electrophoresing the enzyme partially through the capillary and then switching to zero potential. This capillary was left at zero potential for several minutes to allow additional product to accumulate. After this additional amplification step, potential was again applied and the product transported to the detector. Product formed under constant potential appears as a broad peak with a flat plateau. When the voltage is switched to zero at intermediate migration distance, a peak will be observed on top of this plateau. Either the eight of the plateau or the area of the peak may be used to determine enzyme concentration. The lower limit of detection was 4.6.10(-17) mol of glucose-6-phosphate dehydrogenase. PMID- 1430026 TI - Capillary electrophoresis of hemoglobins and globin chains. AB - Capillary isoelectric focusing (cIEF) and free zone capillary electrophoresis were evaluated for separation of native hemoglobins and globin chains. High resolution separations of adult human hemoglobin A, fetal human hemoglobin F, and hemoglobin variants S and C were obtained using cIEF with cathodic mobilization. Absorbance detection in the UV and visible regions were compared, and on-line fast UV or visible-wavelength scanning detection was used to obtain spectral information on separated components. Globin chain analysis was performed on the same hemoglobin species by free zone capillary electrophoresis following precipitation of the protein with acidic acetone. Free zone separations were carried out at low pH in the presence of 7 M urea. PMID- 1430027 TI - Attachment of a single fluorescent label to peptides for determination by capillary zone electrophoresis. AB - Complicated electropherograms are produced in the separation of fluorescently labeled peptides. Incomplete labeling of epsilon-amino groups on lysine residues results in the production of 2n-1 reaction products, where n is the number of alpha and epsilon amino groups in the peptide. A single label is attached to the peptide by first taking the peptide through one cycle of the Edman degradation reaction. All epsilon-amino groups are converted to the phenyl thiocarbamyl and the cleavage step exposes one alpha-amino group at the N-terminus of the peptide; the fluorescent label is attached to the N-terminus. PMID- 1430028 TI - Analysis of antiepileptic drugs in human plasma using micellar electrokinetic capillary chromatography. AB - We describe a method for the simultaneous determination of antiepileptic drugs (ethosuccimide, phenytoin, primidone, phenobarbital, carbamazepine and valproic acid) by micellar electrokinetic capillary chromatography using sodium dodecyl sulphate as the micellar phase. Factors affecting the micellar electrokinetic separation were studied for the quantitative determination of these drugs in human plasma. The confirmation of the peaks and the specificity of the method were investigated by combining multiwavelength detection with micellar electrokinetic capillary chromatography. PMID- 1430029 TI - Study of protein-drug binding using capillary zone electrophoresis. AB - CApillary zone electrophoresis was tested for its suitability for studying protein-drug binding. Three methods were investigated, viz., the Hummel-Dreyer method, the vacancy peak method and frontal analysis. Frontal analysis appeared to be the preferred method. PMID- 1430030 TI - Chiral separations of basic drugs and quantitation of bupivacaine enantiomers in serum by capillary electrophoresis with modified cyclodextrin buffers. AB - Modified cyclodextrin derivatives were evaluated as the buffer additives in capillary electrophoresis of several racemic pharmaceutical bases. Uncoated and polyacrylamide-modified silica capillaries were compared for their effectiveness in the enantiomeric resolution and migration reproducibility of model solutes. Using cationic detergents in the mixed-micellar mode, optimized separations of the racemic drug bupivacaine are demonstrated in a spiked serum sample at the therapeutic level. Precision, linearity and sensitivity of the method appear adequate for reliable quantitation required in pharmacokinetic and clinical studies. PMID- 1430031 TI - Chiral separation by capillary electrophoresis with oligosaccharides. AB - Maltodextrins, i.e., mixtures of linear alpha-(1-4)-linked D-glucose polymers, were found to be effective as chiral electrolyte modifiers to perform direct, rapid separations by capillary electrophoresis of racemic mixtures of 2 arylpropionic acid non-steroidal anti-inflammatory compounds and coumarinic anticoagulant drugs, and also diastereomeric cephalosporin antibiotics. Enantioselectivity seemed to be dependent on an as yet unidentified combination of variables. PMID- 1430032 TI - High-performance capillary electrophoresis of unsaturated oligosaccharides derived from glycosaminoglycans by digestion with chondroitinase ABC as 1-phenyl 3-methyl-5-pyrazolone derivatives. AB - This paper proposes a new method for simultaneous analysis of unsaturated disaccharides derived from glycosaminoglycans by enzymatic digestion with chondroitinase ABC, based on high-performance capillary electrophoresis (HPCE) of their 1-phenyl-3-methyl-5-pyrazolone derivatives. The O-sulphate group is stable in this derivatization, and this method allows reproducible microdetermination of glycosaminoglycans. This paper also demonstrates the applicability of this method to estimation of urinary chondroitin sulphates. Urinary creatinine as an inherent internal standard could also be estimated by HPCE, though in another mode of separation, i.e. ion-exchange electrokinetic chromatography. PMID- 1430033 TI - Separation of natural and synthetic heparin fragments by high-performance capillary electrophoresis. AB - The application of capillary electrophoresis (CE) for the analysis of natural and synthetic low-molecular-mass heparin fragments at low pH is described. It is demonstrated that under the applied conditions the separation is based on charge, charge distribution and molecular mass of the heparin molecules, yielding a high resolution. It is shown that the presence of sodium chloride in the sample solution has hardly any effect on the CE performance. However, the pH of the electrophoresis buffer is a critical parameter. The resolutions obtained with CE and high-performance anion-exchange chromatography (HPAEC) are compared for various heparin fragments and it is concluded that, at least for this type of molecule, CE forms an attractive alternative to HPAEC. PMID- 1430034 TI - Sodium dodecyl sulfate-capillary gel electrophoresis of proteins using non-cross linked polyacrylamide. AB - Proteins with relative molecular masses of 14,000 to 205,000 were separated by sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CGE) using non-cross linked linear polyacrylamide gels on both coated and uncoated fused-silica capillaries. It was determined that viscosity of the acrylamide solution was a major factor affecting column stability with linear acrylamide gels. When the viscosity of the acrylamide solution reaches 100 cP, electro-osmotically driven displacement of the gels is insignificant. Uncoated capillaries provided better resolution, stability, and reproducibility than surface coated capillaries when the concentration of linear polyacrylamide was greater than 4%. At lower gel concentrations, non-cross-linked polyacrylamide is easily displaced from the columns. A calibration plot of log molecular mass vs. mobility with non-linear polyacrylamide was linear, which indicated that resolution was equivalent to that obtained with cross-linked acrylamide. Separations with model proteins indicated that baseline resolution between protein species that vary 10% in molecular mass can be achieved. PMID- 1430036 TI - Indirect photometric detection of polyamines in biological samples separated by high-performance capillary electrophoresis. AB - A rapid separation of polyamines and some related amino acids in cultured tumor cells by high-performance capillary zone electrophoresis with indirect photometric detection is demonstrated. 60 cm x 75 microns I.D. fused-silica capillary was used for the separation and quinine sulfate was used as a background electrolyte (BGE). Several polyamines (putrescine, spermidine and spermine), amino acids (lysine, arginine, histidine) and simple cations (K+, Na+) were easily separated in less than 10 min. Using the indirect photometric detection method, femtomole amounts of polyamines extracted from the tumor cells were detected from nanoliter injection volumes, and the signal response was linear over two orders of magnitude. PMID- 1430037 TI - 9-Fluoreneacetyl-tagged, solid-phase reagent for derivatization in direct plasma injection. AB - We describe here a resin-based derivatization reagent, containing a 9 fluoreneacetyl tag on a controlled-pore substrate, for direct injection analysis of amphetamine in plasma. On-line, pre-column derivatization was performed by direction injection of diluted plasma sample into an sodium dodecyl sulfate containing mobile phase. Amphetamine was trapped in the hydrophobic derivatization column and derivatized at elevated temperature by the activated solid-phase reagent. The derivatized 9-fluoreneacetyl amphetamide was separated by reversed-phase high-performance liquid chromatography with a step gradient and determined by fluorescence detection. The synthesis scheme, characterization, and optimization of the derivatization conditions for the solid-phase reagent are described. The method was evaluated by reproducibility tests and single blind spiking analysis. This solid-phase reagent combined with a surfactant containing mobile phase provided a sensitive and simple procedure for on-line derivatization in direct injection analysis of biological fluids. PMID- 1430035 TI - Assessment of the capabilities of capillary zone electrophoresis for the determination of hippuric and orotic acid in whey. AB - A rapid method was developed for the simultaneous determination of hippuric and orotic acid in rennet whey by capillary zone electrophoresis using an uncoated capillary utilizing a 0.04 M amino-2-methyl-1,3-propanediol (AMPD)-N,N-bis(2 hydroxyethyl) glycine (BICINE) buffer (pH 8.8) with UV detection at 254 and 280 nm. Whey proteins were removed by ultrafiltration. The method was evaluated for external, internal and standard addition procedures for both peak areas and peak heights. The use of an internal standard (sorbic acid) eliminated injection errors and gave, when applied to peak areas, the same levels for hippuric and orotic acid in those obtained with high-performance liquid chromatography. Relative standard deviations were 1-2%. Peak heights gave erratic results owing to sample matrix effects on peak widths. PMID- 1430038 TI - High-performance liquid chromatography of oligosaccharide alditols and glycopeptides on a graphitized carbon column. AB - The chromatographic behaviour of oligosaccharide alditols and glycopeptides containing neutral and acetamido sugars and sialic acid has been investigated on a HyperCarb porous graphitised carbon column. The alditols were substantially retained and could be eluted in 0-25% acetonitrile-0.05% trifluoroacetic acid in 0.05% aqueous trifluoroacetic acid between 3-30 min for mono- to hexasaccharides. Elution patterns were based on both size, charge and linkage such that isomeric compounds could be separated from each other. PMID- 1430039 TI - Rapid method for the determination of glutathione transferase isoenzymes in crude extracts. AB - The analysis of glutathione transferase (GST) isoenzyme patterns is of interest in many fields as hepatic glutathione transferase activity is increased by exposure to a variety of xenobiotics and its isoenzymatic forms are induced differentially. A high-performance liquid chromatography method has been developed for the rapid determination of individual isoenzyme levels in crude extracts using an anion-exchange column connected to an on-line system to automatically detect GST activity with 1-chloro-2,4-dinitrobenzene as the substrate. When 50-200 microliters of a cytosolic fraction of fish liver containing up to 15 mg/ml of protein and less than 2 units of GST were injected, a high resolution and highly reproducible chromatogram was obtained. The activity profile determined automatically showed eight to twelve peaks (depending on the sample) that were quantified and could be classified into three groups. Starting from intact tissue, a complete isoenzyme pattern could be obtained in less than 3 h. The method has been applied to ecotoxicological studies with fish samples. PMID- 1430040 TI - Separation of dideoxyribonucleosides in trace amounts by automated liquid chromatography and capillary electrophoresis. AB - No satisfactory high-performance liquid chromatographic (HPLC) method is currently available for the separation of the major dideoxyribonucleosides (ddNs) and their derivatives. A method involving HPLC has been developed for the separation of five major ddNs [ddA, ddC, ddI, azT and 2',3'-dideoxy-2',3' didehydrothymidine (d4T)]. Elution of the common and modified components of DNA was also examined under the selected separation conditions of HPLC. The elution characteristics of these compounds were studied using serum plasma samples spiked with ddN derivatives. In addition, capillary electrophoresis (CE) was investigated for the separation of ddNs and their derivatives. Picomolar amounts of the five major ddNs and the metabolic product of azT [5'-O-glucuronide-3' azido-3'-deoxythymidine (Glo-azT)] were satisfactorily resolved in 10 min by using a modification of CE. The spectral properties of the ddNs were characterized under different pH conditions and compared with those of their parent deoxyribonucleosides (dNs) because these compounds are commonly measured in HPLC by their spectral properties. The spectra of ddC and ddT derivatives resemble very closely those of dC and dT, but those of ddA and ddI differ to some extent from their parent dNs. The HPLC method was extensively examined for satisfactory resolutions of these compounds. For example, an isocratic elution method, although simple, failed to resolve these compounds and ion-pair chromatography did not offer any advantage. Gradient elution involving buffered solutions and increasing amounts of an organic modifier yielded satisfactory results. Methanol appeared to be the organic modifier of choice. A reversed-phase matrix with smaller than octadecyl alkyl chains did not produce the necessary interactions. Uniform spherical beads of smaller diameter produced superior resolutions. The separation of these compounds on three commercially available columns is discussed. The separation of human plasma samples spiked with dideoxynucleoside derivatives by HPLC was accomplished in ca. 16 min. The presence of the dNs did not interfere in their separations. PMID- 1430041 TI - Chiral high-performance liquid chromatographic separations of vinca alkaloid analogues on alpha 1-acid glycoprotein and human serum albumin columns. AB - Separations of the stereoisomers of a series of tetracyclic and pentacyclic vinca alkaloid analogues having two or three chiral centres were performed on Chiral AGP and Chiral-HSA high-performance liquid chromatographic columns. Phosphate buffers with pH 5-7 containing 5-35% acetonitrile or 2-propanol were used as mobile phases. The results were in accordance with previous binding data obtained with native AGP and on an HSA-Sepharose column. Whereas on Chiral-AGP the retention of the trans isomers having 1(R),12b(S)-indolo[2,3-a]quinolizidine or the corresponding 3(S),16(R)-eburnane absolute configurations was exceedingly high, on Chiral-HSA the trans isomers, independently of their absolute configurations, were more retained. Eburnane-type compounds could also be separated according to the configuration of the chiral centre at position 14. A comparison of the chromatographic properties of the vinca alkaloids on the Chiral AGP and Chiral-HSA columns demonstrates that these compounds are bound with higher affinity to the AGP phase. The AGP column resolves a very broad range of vinca alkaloids compared with the HSA column. Higher stereoselectivity and a much better chromatographic performance were also obtained on the Chiral-AGP column. PMID- 1430042 TI - Enhancement of detection sensitivity and cleanup selectivity for tobramycin through pre-column derivatization. AB - Reversed-phase high-performance liquid chromatography, UV detection and reversed phase solid-phase extraction (SPE) as analytical methods for pharmaceutical compounds face a challenge when the compound is rather polar and lack UV absorptivity. A good example is tobramycin. To overcome these problems, a method has been developed using pre-column derivatization of tobramycin with o phthalaldehyde and automated with an autosampler with microrobotic routines. The detection enhancement of the derivatives was achieved by using fluorescence detection which was forty times more sensitive than using UV detection. Recovery studies of standards and spiked serum samples show that pre-SPE derivatization significantly enhances the recoveries (by at least a factor of 3) and the quality of cleanup over post-SPE derivatization. PMID- 1430043 TI - Column liquid chromatography and microbiological assay compared for determination of cefadroxil preparations. AB - A reversed-phase column liquid chromatographic method was developed for the assay of cefadroxil in bulk drugs and pharmaceutical preparations. An equation was derived showing a linear relationship between peak-area ratios of cefadroxil to dimethylphthalate (internal standard) and the cefadroxil concentration over a range of 0.02-0.8 mg/ml (r = 0.9999). Standard addition recoveries were generally greater than 97.7%. The coefficients of variation in the within-day assay were between 0.36 and 0.65, and in the between-day assay was 0.71%. The column liquid chromatographic assay results were compared with those obtained from a microbiological assay, which indicated that the proposed method is a suitable substitute for the microbiological method for potency assays and stability studies of cefadroxil preparations. PMID- 1430045 TI - Determination of Penicillium roqueforti toxin by reversed-phase high-performance liquid chromatography. AB - A method for the detection and quantification of Penicillium roqueforti toxin (PRT) using reversed-phase high-performance liquid chromatography has been established. The limit of quantitation of this method was 3 ng of PRT, while the limit of detection was 2 ng of toxin. The precision of the analysis based on numerous runs was good. Retention times for PRT were highly reproducible with an average coefficient of variation of about 1.6%. Analysis of PRT in liquid and solid samples showed no interference of the sample matrix. The accuracy of the method was 98.6%, with mean PRT recoveries of 96.8%, and 100.4% for the spiked culture medium and blue cheese extracts, respectively. PMID- 1430044 TI - Chiral separation of nipecotic acid amides. AB - 1-Decyl-3-(N,N-diethylcarbamoyl)piperidine (1) and alpha,alpha'-bis[3-(N-benzyl-N methylcarbamoyl)piperidinol]-p-xyle ne (2) represent mono-N-substituted and bis-N substituted carbamoylpiperidines, or nipecotic acid amides, respectively. Initially, several attempts were made to resolve these compounds using beta cyclodextrin, cellulose carbamate and Pirkle-type columns. However, the interactions of the stereoisomers of the two compounds with these stationary phases did not differ enough to permit satisfactory separations. Baseline resolution was achieved using an alpha 1-acid glycoprotein (AGP) chiral column. The mobile phase was phosphate buffer (pH 7.0). Tetrabutylammonium (TBA) was used as the cationic modifier and ethanol as the uncharged modifier. Circular dichroism was used to identify the enantiomers. Compound 1 was resolved into positive and negative enantiomers and 2 into positive and negative enantiomers and a meso diastereomer. The influence of pH, buffer ionic strength, cationic and uncharged modifier concentrations on retention, chiral selectivity and resolution were evaluated. Based on the results, it is suggested that both ionic and hydrophobic interactions may be responsible for retention and resolution. PMID- 1430046 TI - Chromatographic analysis of cis- and trans-mevinphos in poisoned wildlife. AB - A method is described for the analysis of the cis- and trans-isomers of mevinphos in baits and avian tissues. The procedure involves extraction of the mevinphos isomers with acetone-dichloromethane (1:1) followed by clean-up on alumina. Bait samples were initially screened by thin-layer chromatography and identity of extracts confirmed by infrared spectrophotometry and gas chromatography-mass spectrometry. PMID- 1430047 TI - Solid-phase extraction and HPLC determination of 4-vinyl guaiacol and its precursor, ferulic acid, in orange juice. AB - This study is undertaken to develop a simplified, rapid method to determine both immediate and potential off odors due to 4-vinyl guaiacol and its odorless precursor, ferulic acid, from a single sample preparation and chromatographic analysis. Orange juice sample preparation consists of a simple, C18 solid phase extraction. Utilizing a 5-microns, 25-cm, C18 column, both compounds can be separated within 40 min using a one-step, linear gradient beginning with an aqueous 12% tetrahydrofuran (THF)-5% acetonitrile mixture and ending with 35% aqueous THF. Hesperidin and nariutin have been identified as the compounds that interfered with the ultraviolet (UV) determination of sinapic and caffeic acids. Fluorescence detection with wavelength programming offers optimal sensitivity and selectivity. Recoveries of 4-vinyl guaiacol and ferulic acid range from 90 to 103%. Detection limits are 1 ppm and 5 ppm for ferulic acid and 4-vinyl guaiacol, respectively. Other hydroxycinnamic acids such as coumaric, sinapic, and caffeic acids may also be determined from the same chromatogram. PMID- 1430048 TI - Fractionation by SFE and microcolumn analysis of the essential oil and the bitter principles of hops. AB - Supercritical fluid extraction (SFE) is evaluated and optimized for the enrichment and fractionation of the essential oil and the bitter principles of hops (Humulus lupulus), both of which contribute to the flavor of beer. Profiles of the essential oil of different hop varieties are compared. The bitter principles, the humulones and lupulones, are analyzed by miniaturized liquid chromatography (micro-LC) and by micellar electrokinetic chromatography (MEKC). PMID- 1430049 TI - GC-MS identification of amine-solvent condensation products formed during analysis of drugs of abuse. AB - The use of methanol or ethanol as the injection solvent for the gas chromatographic-mass spectral (GC-MS) analysis of low molecular weight amine drugs of abuse results in the formation of additional components in the sample. Primary amines, such as amphetamine, 3,4-methylenedioxyamphetamine, and phenethylamine, yield imines upon injection as methanol or ethanol solutions. In methanol, the imine formed has a mass that is 12 mass units higher than the parent compound. In ethanol, the products formed have 26 additional mass units. Secondary amines appear to undergo methylation under similar conditions with methanol as the injection solvent. These products are absent from the analysis of equivalent amine samples dissolved in chloroform. PMID- 1430050 TI - Multiresidue analysis of anabolic agents in muscle tissues and urines of cattle by GC-MS. AB - The illegal use of anabolic steroids in livestock breeding has taken enormous proportions the last few decades. To protect the consumer against possible harmful effects due to the consumption of contaminated meat or meat products, a multiresidue analysis of anabolic steroids has been developed for muscle tissues and urine. The pretreatment of the meat and urine samples consists of an enzymatic digestion, liquid or solid-phase extraction, and finally high performance liquid chromatography (HPLC) fractionation. Five fractions or windows are collected, each containing a number of analytes. The residues are derivatized prior to the detection by gas chromatography-mass spectrometry (GC-MS). Both gas chromatographic retention data and mass spectral data are used for identification of nortestosterone, testosterone, estradiol, ethynylestradiol, trenbolone, zeranol, diethylstilbestrol, boldenone, methandienone, methyltestosterone, megestrol acetate, chlormadinone acetate, medroxyprogesterone acetate, chlorotestosterone, progesterone, and chlorotestosterone acetate. The limit of detection varies from matrix to matrix and from analyte to analyte but is, in the most favorable case, on the order of 0.3 ppb (micrograms/kg). PMID- 1430051 TI - Separation of glucuronides from urine by coupled-column separation using underivatized silica as precolumn. AB - Glucuronides are separated from urine by coupled-column separations (CCSs). The fraction containing the glucuronide(s) is transferred on-line from a silica precolumn to the analytical column (octadecyl derivatized silica), enriched, and separated by ion-pair chromatography. The retention and selectivity on the precolumn are controlled by pH, buffer components, organic modifier, and ion-pair agent. After the injection of filtered urine samples, glucuronides with different chemical properties can be separated. The total analysis of morphine-3 glucuronide and morphine-6-glucuronide is accomplished in less than six minutes, with UV detection at 210 nm. PMID- 1430052 TI - Serological detection of HBeAg and anti-HBe using automated microparticle enzyme immunoassays. AB - Fully automated microparticle enzyme immunoassays (EIA) were developed for the detection of HBeAg (IMx HBe) and antibodies against HBeAg (IMx anti-HBe), respectively. Specimens from blood donors, diagnostic and hospital patients and individuals with a variety of infectious and immune diseases were tested both in house and at four clinical sites. The overall agreement between IMx HBe and Abbott HBe RIA/EIA was 99.7% (2985 of 2994) and between IMx anti-HBe and anti-HBe RIA/EIA was 95.8% (2330 of 2432). Almost all anti-HBe discordant specimens (94.1%, 96 of 102) were reactive by IMx anti-HBe but negative by anti-HBe RIA/EIA. off anti-HBe discordant specimens were also reactive for anti-HBc. The IMx anti-HBe assay was 2- to 4-fold more sensitive than the current RIA as determined by serial dilution of anti-HBe reactive specimens. The ability of these IMx assays to detect HBeAg and anti-HBe in 199 HBsAg reactive specimens was also evaluated. 43.7% (87 of 199) and 66.3% (132 of 199) specimens were reactive for HBeAg and anti-HBe by IMx, respectively. Only one specimen was negative for both IMx assays compared to 14 (7.0%) non-reactive for both HBe and anti-HBe RIA. There were 24 specimens (12.1%) positive for both HBeAg and anti-HBe by IMx compared to 1 (0.5%) positive by the corresponding RIAs. This increased detectability of anti-HBe in HBsAg carriers using IMx anti-HBe may result from increased sensitivity for 'free' anti-HBe and/or increased ability to detect anti HBe in immune complex. IMx anti-HBe also detected more reactives among volunteer blood donor specimens reactive for anti-HBc but negative for HBsAg (55.5%, 86 of 155), compared to RIA (38.7%, 60 of 155). IMx anti-HBe may be useful in confirming prior exposure to HBV in blood screened positive by Corzyme. PMID- 1430053 TI - Affinity purification of the structural proteins of a fish Rhabdovirus by the use of monoclonal antibodies. AB - A simple procedure for optimization of affinity chromatography is described for parallel purification of four structural proteins of viral haemorrhagic septicaemia virus. Monoclonal antibodies to be used as affinity reagents were characterized initially with respect to elution conditions by enzyme-linked immunosorbent assay. Subsequently, immobilized antibodies were tested in a microscale nonradioactive direct immunoprecipitation assay, in order to establish optimal conditions for affinity purification of the viral proteins. PMID- 1430054 TI - An evaluation of two simple synthetic peptide based anti-HIV assays. AB - Two simple synthetic peptide based assays for anti-HIV (Agen SimpliRED and Genetic Systems GENIE) were evaluated for their ability to distinguish samples that contained anti-HIV-1 from samples that did not. The anti-HIV negative samples were from uninfected subjects that had either given false positive reactions on existing screening assays or indeterminate reactivity on Western blot. The anti-HIV-1 positive samples had been shown to contain antibody by a number of assays, and clinical details of the patients were known. The SimpliRED and GENIE assays demonstrated similar performances, with sensitivities of 99.77% and 100%, and specificities of 97.78% and 99.16%, respectively. PMID- 1430055 TI - Immuno-electron microscopical detection of tomato spotted wilt virus and its nucleocapsids in crude plant extracts. AB - Tomato spotted wilt virus (TSWV) particles were identified in thin sections and in crude extracts of leaves from plants infected with different TSWV isolates, using gold labelled protein A and antibodies prepared against purified virus particles or against nucleocapsid preparations. In addition, both in thin sections and in dip preparations aggregates were detected using either gold labelled antiserum. These aggregates were not detected using antisera against envelope proteins or against the non-structural protein NSs. They were the only detectably labelled material in preparations made from plants infected by morphologically defective isolates of TSWV, i.e. isolates that did not produce enveloped particles. The aggregates were discerned in dip preparations as cloudy amorphous structures having a cottonwool boll-like appearance. These 'cotton bolls' were interpreted as being the in vitro structures of the nucleocapsid aggregates occurring in plant cells infected by isolates maintained by mechanical inoculation and are the only structures in cells infected by morphologically defective isolates (Ie, 1982; Kitajima et al., 1992). The detection of the 'cotton boll-like' structures in crude extracts provides an adequate and rapid method to establish the presence of nucleocapsid aggregates in cells of infected plants, irrespective of whether they are infected by morphologically defective isolates or not. PMID- 1430056 TI - Development of a sensitive ELISA for HIV-1 p24 antigen using a fluorogenic substrate for monitoring HIV-1 replication in vitro. AB - A two-site sandwich fluorescent-ELISA was optimized for the detection of HIV-1 p24 antigen produced by lymphoid cells infected with HIV-1 in vitro. To improve the sensitivity of the ELISA, a combination of streptavidin-beta-galactosidase and a fluorogenic substrate (4-methylumbelliferyl-beta-D-galactopyranoside) was employed for the enzymatic detection stage. Using recombinant p24 as standard antigen, a two-step assay detected as little as 0.7 pg/ml (3.10(-14) M) with an upper limit of 10,000 pg/ml. This detection range (approx. 50-70-times greater than ELISAs using a chromogenic detection) permitted an accurate and straightforward quantitation of p24 in culture supernatants. Overall, the fluorescent-ELISA had increased detectability, sensitivity and efficiency over existing ELISAs for HIV-1 p24. PMID- 1430057 TI - Type-specific identification of influenza viruses A, B and C by the polymerase chain reaction. AB - The aim of this study was to develop a polymerase chain reaction for specific detection of influenza A, B, and C RNA genomes. Three primer sets were selected from conserved regions of the genome coding for the non-structural proteins and were tested on 61 influenza A (22 H1N1, 9 H2N2, and 30 H3N2), 11 influenza B, and three influenza C isolates. Specific amplified products were obtained with all these strains after electrophoresis on a 2% agarose gel. The specificity of the reaction was increased by hybridization with oligonucleotide probes. When nucleic acids from a variety of micro-organisms from the respiratory tract were subjected to the PCR with these primers, no specific amplified products were generated. The sensitivity of the technique was found to be at the subpicogram level. The RNA PCR was applied to 21 clinical specimens from patients with a culture/IF proven influenza infection. Six influenza A positive patients and 13 influenza B positive patients could be confirmed in the RNA-PCR. In two cases, influenza B positive IF specimens were found negative by the PCR. No virus could be isolated on eggs or tissue culture from these samples. RNA-PCR is a specific and sensitive technique for the detection of influenza virus genomes. PMID- 1430058 TI - A solid-phase enzyme-linked assay for influenza virus receptor-binding activity. AB - Receptor-binding properties of influenza viruses are usually characterized by the ability of viruses to interact with more or less defined sialic acid-containing carbohydrates, glycoproteins, or glycolipids assayed by haemagglutination (HA) or HA inhibition (HAI) tests. To overcome some drawbacks of these tests a solid phase enzyme linked assay analogous to sandwich ELISA was developed. The virus is adsorbed specifically to the well of plastic microtitre plates coated with fetuin, and the binding of horseradish peroxidase (HRP)labelled sialylglycoproteins (SGPs) by the solid phase-attached virions is measured. The binding of unlabelled compounds is measured by competition with the attachment of a standard fetuin-HRP conjugate. The assay is easy to perform, quantitative (allows the determination of affinity constants), and sensitive (even the weak binding of free N-acetylneuraminic acid with Kd about 10(-1)-10(-2) M(-1) can be studied). Due to a higher stability of components of the present test system, as compared to red blood cells, the influence of pH, ionic strength, and other factors on virus-receptor interaction can also be investigated. PMID- 1430059 TI - Persistence of specific IgM and low avidity specific IgG1 following primary rubella. AB - Persistence of specific IgM in sera following primary rubella infection was compared with the maturation of the specific IgG1 response. 206 sera, from 171 patients with primary rubella, taken 1 day to 2.5 years after onset of illness, were tested. Rubella-specific IgM was detected by M-antibody capture radioimmunoassay in 100% of sera taken 15-28 days after onset, but in only 9% taken 3-4 months after onset. However, using the diethylamine (DEA) shift value (DSV) method, low avidity specific IgG1 was detected in 91% sera taken at 3-4 months and at 5-7 months 21% of sera remained positive. Using an avidity index method, with urea in the wash buffer, none of the sera were positive for low avidity specific IgG1 beyond 3 months after onset. With DEA in the wash buffer, the number of sera positive rose to 38% at 3-4 months. Thus, the DSV method for detecting low avidity specific IgG1 is a useful additional test for confirming or refuting a diagnosis of primary rubella and is of particular value for assessing pregnant patients. PMID- 1430060 TI - A sensitive assay for detection and measurement of neutralising antibody to human immunodeficiency virus. AB - An assay based on the inhibition of syncytium formation in C8166 cells was developed to measure low levels of neutralising antibody (NT-AB) to human immunodeficiency virus (HIV) and to detect cross-reactivity between virus strains. The relationship between virus challenge and antibody titre was represented by a tripartite curve which was essentially linear over moderate levels of virus input. Based on these findings, antibody titres were standardised against 100 TCID50 of challenge virus. However, lower virus inocula were found to detect minimum levels of antibody. Reproducibility of antibody titres between tests was high, with variation generally lying within one dilution step. The improved sensitivity of the technique allowed detection of NT-ABs in animals immunised with immune-stimulating complexes (ISCOMS) incorporating HIV antigens. Consistent levels of cross-reactivity between HIV strains was demonstrated, indicating the presence of distinct viral groups, from which dominant isolates may be chosen for use in vaccination studies. PMID- 1430061 TI - 3' terminal nucleotide sequence of human astrovirus type 1 and routine detection of astrovirus nucleic acid and antigens. AB - Human astrovirus type 1 was purified by caesium chloride density-gradient centrifugation and the virus was located using an immunodot blot technique with polyclonal rabbit serum, which reacted with all five serotypes. The virus banded with a density of 1.33 g/ml. RNA was extracted from the purified virus, converted into double-stranded cDNA, using an oligo(dT) primer, and cloned into plasmid and M13 vectors. The sequence of the 3' end of astrovirus RNA adjacent to the poly(A) tract was determined. This sequence showed no significant homology with the equivalent region of other positive-sense RNA viruses. Synthetic oligonucleotide primers were designed to amplify specifically astrovirus type 1 RNA in a polymerase chain reaction. PMID- 1430062 TI - A streptavidin-biotin-enhanced nitrocellulose enzyme immunoassay for the detection of rhabdovirus of penaeid shrimps from infected animals. AB - A streptavidin-biotin-enhanced nitrocellulose enzyme immunoassay was developed for the detection of the rhabdovirus of penaeid shrimps (RPS) in the tissues of infected animals. Initial tests indicate that the assay was capable of detecting as few as ten plaque-forming units of virus. PMID- 1430063 TI - A highly sensitive immunocapture polymerase chain reaction method for plum pox potyvirus detection. AB - A highly sensitive assay, based on polymerase chain reaction amplification of cDNA synthesized from the viral RNA of antibody-captured viral particles, has been developed for plum pox potyvirus (PPV) detection. The reaction, called immunocapture/PCR (IC/PCR), yields a specific 243-bp product. The immunocapture step, by allowing the use of large sample volumes and by the viral particle prepurification it achieves, dramatically increases the sensitivity of the assay. As few as 8000 target viral particles per ml of plant extract could be detected by IC/PCR. When compared to direct PCR (Wetzel et al., 1991), molecular hybridization using 32P-labeled cRNA probes and ELISA, this result corresponds to a 250-fold, 625-fold and 5000-fold increased sensitivity, respectively. The high sensitivity of IC/PCR was confirmed during an indexing trial with field samples collected from naturally infected trees. This very powerful technique should have wide ranging applications for the detection of a number of other viruses and pathogens for which specific antisera and sequence data are available. PMID- 1430064 TI - Is the IEMA combined incubator/shaker device preferable to a waterbath for incubating enzyme immunoassays? AB - An incubator/shaker device proved to be a convenient alternative to a waterbath for the incubation of enzyme immunoassays (EIA). The device achieved effective and even heat transfer. In two of five EIAs it increased reactivity and in three of five EIAs it slightly increased the discrimination between seronegative and seropositive specimens though, for the samples investigated, extra sensitivity was not thereby achieved. At a high shaking frequency (1400 rpm) there was cross contamination between wells, but this did not occur at 900 rpm. The relative contributions of heating and of shaking to the incubation of EIAs deserve further investigation. PMID- 1430065 TI - A novel, spectrophotometric microneutralization assay for respiratory syncytial virus. AB - We describe a simple and rapid microneutralization assay for respiratory syncytial virus (RSV) based on the colorimetric quantitation of the conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to a formazan product by the mitochondria of viable cells. Conditions for RSV infectivity were first optimized for sensitivity and reproducibility based on cell density and on RSV concentration as a function of multiplicity of infection (MOI) and time post infection and the resulting optical densities were shown to be inversely proportional to MOI. For RSV neutralization, dilutions of heat-inactivated human plasma were preincubated with RSV and complement prior to infection of cells in microtiter plates. Following MTT dye conversion, 50% RSV neutralization titers were determined by linear regression analysis of the optical density values and endpoints were markedly influenced by MOI. The MTT-based assay was shown to be comparably sensitive to the plaque reduction assay for quantitation of neutralizing antibody, but more readily adaptable to the screening of a large number of samples. Finally, we demonstrated that the MTT microneutralization assay for RSV was useful for quantitation assay of neutralization activity in sera of mice and cotton rats. PMID- 1430066 TI - A statistical method for the detection of false positives and false negatives in microtitre format PCR assays. AB - A method is described which can be used to determine whether a series of PCR reactions carried out in a microtitre plate are inherently unlikely to have occurred by chance, and hence to show 'false' results. The method is an extension of the familiar 'runs test' which can be used for tube-based PCRs. A Monte Carlo simulation program is discussed which can be used to generate expected probability distributions for either symmetric or asymmetric plate designs. In addition, systematic departures from a random pattern due to 'edge effects' can be detected. PMID- 1430067 TI - Viral susceptibility of an immortalized human microvascular endothelial cell line. AB - CDC/EU.HMEC-1 is the first immortalized human microvascular endothelial cell line that retains morphologic, phenotypic, and functional characteristics of a normal human microvascular endothelial cell. This study evaluates a variety of viruses and their effects on this human endothelial cell line. The data indicate that adenoviruses, some herpesviruses, reoviruses and most picornaviruses grow well in HMEC-1, with distinctive cytopathic effects. The paramyxoviruses, however, do not appear to propagate, nor does HIV. The findings indicate that microvascular endothelial cells may act as a reservoir of these viruses; it also suggests the possibility that microvascular endothelium could be involved in the processing and presentation of antigen to immune cells. PMID- 1430068 TI - Highly sensitive digoxigenin-labelled DNA probe for the detection of potato spindle tuber viroid. AB - A molecular probe pSPAv6.2(+), with concatameric insert representing 6.2-times repeated copy of potato spindle tuber viroid (PSTV) RNA, was labelled with digoxigenin and used to detect PSTV by dot-blot hybridization assay. The probe was highly sensitive and specific, detecting as little as 2.5 pg of PSTV RNA. Both severe and mild PSTV strains were detectable in 64-512-times diluted crude extracts from infected tomato leaves, and potato leaves, sprouts, and seeds. For extraction of plant tissue three buffers were compared to determine the lowest non-specific background and the highest sensitivity. The results showed that the digoxigenin-labelled probe is as sensitive as the 32P-labelled probe and can replace radioactive techniques in PSTV detection. With such high sensitivity, the probe is also potentially useful for detecting the viroid in composite samples of mass-indexing programs. PMID- 1430069 TI - Recombinant parvovirus B19 capsids as a new substrate for detection of B19 specific IgG and IgM antibodies by an enzyme-linked immunosorbent assay. AB - A new enzyme-linked immunosorbent assay for the detection of B19-specific IgG and IgM antibodies was established using B19 capsids synthesized in a baculovirus expression system. These B19 capsids, consisting of either coat protein VP2 alone or of both VP1 and VP2, have been shown to be similar to native virus in size and appearance. The results obtained for the detection of B19-specific antibodies showed good correlations with a radioimmunoassay which uses native B19 virus and an immunofluorescence assay based on insect cells expressing coat protein VP1. The course of the antibody response could be followed by determining the titers of sequential serum samples taken after a recent B19 infection. Both types of recombinant capsids form an excellent source of antigen for the detection of both B19 IgG and IgM antibodies and are a very promising substitute for native virus. PMID- 1430070 TI - Competitive polymerase chain reaction using an internal standard: application to the quantitation of viral DNA. AB - A general strategy for the construction of an internal standard for the polymerase chain reaction (PCR) is described together with its application in the evaluation of clinical samples. This internal standard is a plasmid containing a modified target sequence that is co-amplified with the native target using the same set of primers. The co-amplification reaction will generate two fragments of different size that are readily separated without the need for restriction enzyme digestion. Thereafter, they are detected and quantitated by hybridization to the same probe. Detection of HIV proviral DNA was chosen as a model for this competitive PCR. The assay proved to be a sensitive tool for the detection of PCR inhibitors and allowed quantitation of HIV with a 20-30% variation coefficient. Despite limitations that appear inherent to the amplification process, internal standards appear to be useful tools for quantitative analysis by PCR. PMID- 1430071 TI - Comparison of eight different procedures for harvesting avian reoviruses grown in Vero cells. AB - 14 avian reovirus isolates adapted to replicate in an African green monkey (Vero) cell line were studied for the nature of their replication. The growth curves of 5 viruses showed them to be highly cell-associated in Vero cells. Different procedures were examined for releasing the cell-associated virus following propagation in Vero cells, including several freeze-thaw cycles, treatment with sterile distilled deionized water (ddH2O), freon extraction, and trypsin treatment. Treatment of virus infected cultures with ddH2O was the most effective, and trypsin treatment was the least effective procedure for dissociation of virus from cells. Treatment of virus infected cultures with ddH2O is a simple and effective procedure which can be used where large amounts of virus are required for experimental purposes. PMID- 1430072 TI - A rapid chemiluminescent detection method for barley yellow dwarf virus. AB - Barley yellow dwarf virus (BYDV-PAV-IL) was detected with biotinylated in vitro transcript cDNA using a chemiluminescent substrate on nylon membranes. Signals were detected on X-ray film and quantified using either a densitometer or an ELISA plate reader. The time required for sample preparation was reduced so that the entire protocol could be completed in two days. The in vitro transcript probes could detect 1 ng of purified virus and as little as 1 microliter of sap extracts prepared from infected oat shoots. PMID- 1430073 TI - The assessment of nucleotide sequence diversity by the polymerase chain reaction is highly reproducible. AB - The polymerase chain reaction (PCR) is often used to assess the diversity of viral nucleotide sequences present in various biological samples (e.g., blood and tissues). However, it is not clear how reproducible this approach may be. DNA was extracted from the peripheral blood lymphocytes of a macaque that had been infected, experimentally, with SIVmac251-32H 6 months previously. The nef gene was then amplified by the PCR on three separate occasions from this same template preparation. A panel of clones was prepared from the product of each PCR, the entire nef gene was sequenced and the sequences obtained compared with each other. Phenogram analysis revealed that within each panel the same degree of sequence diversity was observed between clones. Furthermore, when the sequences obtained from all three panels were compared, the overall sequence diversity observed was no greater than that observed for each panel individually. These data indicate that the analysis of sequence diversity in SIV 'quasi-species' populations by the PCR is reliable and, more important, reproducible. PMID- 1430074 TI - A nylon membrane enzyme immunoassay for rapid diagnosis of influenza A infection. AB - A new membrane-enzyme immunofiltration assay (MIFA) was developed for rapid diagnosis of influenza A infection. The pretreated specimens were dispensed into a 1.2 micron Biodyne B nylon membrane-bottomed microplate and vacuum filtration was applied. Blocking solution, peroxidase-conjugated anti-influenza A nucleoprotein monoclonal antibody, washing buffer and substrate were added in that order. The assay was completed within 30 min. Out of 103 nasopharyngeal swabs collected in transport medium, 31 isolates of influenza A virus were obtained and 22 specimens were detected directly by the MIFA technique. The 9 isolation-positive MIFA-negative specimens required 6 days or more for viral detection in cell culture, and probably contained a very low quantity of virus. The 72 cell culture negative specimens were also negative by MIFA. Comparison with a classical immunocapture assay (ICA) gave a better sensitivity for MIFA, as only 15/103 specimens were positive by ICA. MIFA is a rapid test with 71% sensitivity and 100% specificity. It was also very useful to test the cell culture supernatants, as a sensitivity of 100% was obtained with MIFA when the immunofluorescence technique was positive. The same technique could be readily carried out on the same plate for other respiratory viruses since capture antibody is not used. PMID- 1430075 TI - Clinical review 39: Paget's disease of bone. PMID- 1430076 TI - Role of insulin-like growth factor-1 in reversing catabolism. PMID- 1430077 TI - Effect of increasing doses of recombinant human insulin-like growth factor-I on glucose, lipid, and leucine metabolism in man. AB - The metabolic effects of recombinant human insulin-like growth factor-I (IGF-I) were assessed in five groups of normal male overnight-fasted volunteers receiving infusions of either 0, 5, 7.5, 15, or 30 micrograms/kg.h IGF-I during 8 h, resulting in total plasma IGF-I concentrations 127 +/- 7, 247 +/- 30, 389 +/- 39, 573 +/- 62, 620 +/- 105 ng/ml, respectively. Glucose consumption (euglycemic glucose clamp) increased dose dependently during IGF-I infusion (P < 0.001) up to 6.7 +/- 1.3 mg/kg. min in the 30 micrograms/kg.h group. Plasma triglyceride concentrations decreased with increasing doses of IGF-I (P < 0.03); the fall was 43% in the 30 micrograms/kg.h group. Plasma free fatty acid concentrations decreased during 7.5, 15, and 30 micrograms/kg.h IGF-I by 23%, 34%, and 48%, respectively. IGF-I lowered plasma beta-hydroxybutyrate concentrations in a dose dependent manner (P < 0.025). Plasma concentrations of leucine and alpha ketoisocaproate decreased dose dependently (P < 0.001 and P < 0.015). Whole body leucine flux (1-13C-leucine infusion technique) decreased with increasing doses of IGF-I by 41% during 30 micrograms/kg.h, indicating decreased whole body protein breakdown. Leucine oxidation into 13CO2 decreased with increasing doses of IGF-I (P < 0.045) by 57% in the 30 micrograms/kg.h group, suggesting inhibition of irreversible loss of leucine. Plasma C-peptide and insulin concentrations decreased dose dependently (P < 0.005 and P < 0.02), indicating diminished insulin secretion. Thus, acute elevation of plasma IGF-I concentrations in man results in metabolic effects which are qualitatively similar to those described previously of insulin. PMID- 1430078 TI - Low dose recombinant human insulin-like growth factor-I fails to affect protein anabolism but inhibits islet cell secretion in humans. AB - The in vivo effects of recombinant human insulin-like growth factor-I (rhIGF-I) on whole body protein metabolism were studied to ascertain whether rhIGF-I has comparable effects as those reported with rhGH use in humans. The doses of rhIGF I chosen achieved similar plasma IGF-I concentrations as those achieved after 7 days of rhGH injections. Eight normal volunteers were studied using [1-13C]- and [1-14C]leucine tracers, before, 4 h, and 28 h after a continuous infusion of rhIGF-I at 5 micrograms kg-1 h-1 (n = 6) and 10 micrograms kg-1 h-1 (n = 2). Two additional subjects were studied in a protein catabolic state after 7 days of high dose (0.8 mg kg-1 day-1) glucocorticosteroid administration. Plasma concentrations of rhIGF-I were similar using either 5 or 10 micrograms kg-1 h-1 and increased to values approximately 300% above baseline by 28 h of infusion. No decrease in the plasma glucose concentration was observed during the 28-h infusion; however, plasma insulin, C-peptide, and glucagon concentrations significantly decreased, whereas plasma free fatty acids were not affected. No changes were observed in the rate of proteolysis (as estimated by the rate of leucine appearance), the rate of leucine oxidation, or the rate of protein synthesis in the absence or presence of glucocorticosteroid treatment. Plasma concentrations of insulin-like growth factor binding protein-3 did not change during the rhIGF-I infusion whereas they increased 50% in subjects who received rhGH, and in whom rhGH caused a potent protein anabolic effect. These results suggest that rhIGF-I may have a somatostatin-like effect. In addition, we found that rhIGF-I infusion is insufficient to promote protein anabolism. This may be due to the failure of rhIGF-I alone to induce a pivotal GH-dependent cofactor(s) necessary for IGF-I to elicit an anabolic effect on protein metabolism in humans. PMID- 1430079 TI - Temporal pattern of pancreatic insulin and C-peptide secretion and of plasma glucose levels after nutritional stimulation. AB - The dependency of the secretory pattern of insulin and C-peptide on either oral ingestion of the energy substrates glucose and protein or gastric distension was determined in nine healthy male subjects. To analyze secretion dynamics, high frequency blood sampling, computed estimation of individual hormone half-lives, deconvolution of data, and pulse analysis of the deconvoluted data by the Cluster program were used. After stimulation with oral glucose and protein, baseline insulin, C-peptide, and glucose levels increased in parallel, forming two or three large increases (macropulses), with a mean duration of 63.8 min. The frequency of high frequency insulin and C-peptide pulses was unchanged, whereas a significantly increased amplitude formed the basis of insulin/C-peptide macropulses after both oral stimulations. No changes in baseline insulin/C peptide concentrations or in amplitude or frequency were observed after a challenge with 400 mL H2O (n = 3). Gastric distension with an equal volume of H2O (400 mL) did not influence pancreatic hormone secretion. Insulin and C-peptide secretions were pulsatile, with a frequency of approximately one pulse per 12 min correlated to C-peptide pulses. When calculated by multiple regression analysis glucose, insulin and C-peptide plasma levels increased simultaneously after the challenge with either glucose or protein, suggesting a neuronal or humoral intestinal-pancreatic regulation of pancreatic hormone secretion. These findings suggest that high frequency insulin and C-peptide pulses form the basis of insulin and C-peptide plasma levels after meal stimulation. PMID- 1430081 TI - Acute effects of testosterone infusion and naloxone on luteinizing hormone secretion in normal men. AB - To evaluate the role of endogenous opioid pathways in the acute suppression of LH secretion by testosterone (T) infusion in men, we studied eight normal healthy volunteers who received a saline infusion, followed 1 week later by a T infusion (960 nmol/h) starting at 1000 h and lasting for 33 h. After 2 h of infusion (both saline and T), four iv boluses of saline were given hourly, and after 26 h of infusion, four hourly iv boluses of naloxone were given. Blood was obtained every 15 min for LH and every 30 min for T. T infusion increased the mean plasma T concentration 2.1-fold (18.7 +/- 2.1 to 39.5 +/- 3.5 nmol/L, saline vs. T infusion, P < 0.01). The mean plasma LH concentration was 7.9 +/- 0.5 IU/L during the saline control study and was decreased to 6.9 +/- 0.6 IU/L by the infusion of T (P < 0.05). LH pulse frequency was similar during both saline and T infusions (0.48 +/- 0.02 vs. 0.43 +/- 0.04 pulses/man.h, saline vs. T infusion). The mean LH pulse amplitude decreased from 4.3 +/- 0.4 IU/L during saline infusion to 3.3 +/- 0.2 IU/L during T infusion (P < 0.05). The administration of naloxone increased the mean plasma LH concentration significantly during saline infusion (7.6 +/- 0.4 to 10.0 +/- 0.9 IU/L, saline vs. naloxone boluses, P < 0.01), but not during T infusion (6.9 +/- 0.6 vs. 7.3 +/- 0.6 IU/L). LH pulse frequency increased significantly after the administration of naloxone during both saline and T infusions (0.54 +/- 0.04 to 0.71 +/- 0.08 pulses/man.h, saline vs. naloxone boluses during saline infusion, and 0.46 +/- 0.08 to 0.60 +/- 0.07 pulses/man.h during T infusion; P < 0.05). LH pulse amplitude was suppressed by T infusion, but administration of naloxone did not reverse this suppression. The mean amplitude of the LH response to exogenous GnRH (250 ng/kg) was decreased by T infusion from 48 +/- 13.5 to 31.2 +/- 8.5 IU/L (P < 0.01). Therefore, in men, the administration of naloxone increases LH pulse frequency during both saline and T infusions, but the acute suppression of LH pulse amplitude seen with T infusion was not reversed by naloxone. This pattern contrasts sharply with the effects of T infusion in pubertal boys, as elucidated by our earlier studies. The negative feedback effects of T on LH secretion are primarily hypothalamic in early pubertal boys and change to pituitary suppression in men. PMID- 1430080 TI - Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester. AB - Due to unfavorable pharmacokinetics of the available androgen esters for substitution therapy of male hypogonadism, there is a demand for new testosterone (T) preparations producing constant serum levels in the physiological range. To assess the pharmacokinetics and pharmacodynamics of the new ester testosterone buciclate (TB) [20 Aet-1] in hypogonadal men a clinical phase I-study was performed. After two control examinations 8 male patients with primary hypogonadism were randomly assigned to 2 treatment groups (n = 2 x 4) given single doses of either 200 (group I) or 600 mg (group II) TB im. Blood samples were obtained 1, 2, 3, 5, and 7 days post injection and then weekly in the course of 4 months. In group I serum androgen levels did not rise to normal values. However, in group II androgens increased significantly and were maintained in the normal range up to 12 weeks with maximal serum levels of 13.1 +/- 0.9 nmol/L (mean +/- SE) in study week 6. No initial peak release of T was observed in either study group. Pharmacokinetic analysis revealed a terminal elimination t1/2 beta of 29.5 +/- 3.9 days and a mean residence time of 65.0 +/- 9.9 days in group II. In one patient in group II dihydrotestosterone levels slightly exceeded the upper normal limit during the study course. Sex hormone-binding globulin remained unchanged and estradiol serum levels never exceeded the normal range in any patient. In group II gonadotropins were significantly suppressed, whereas no change was seen in group I. A significant increase in body weight, hematological parameters, and libido/potency was observed after TB injection which was more pronounced in the higher dose group. Regardless of the dose administered, no significant change was seen in uroflow, prostate volume measured by transrectal ultrasonography, or prostate specific antigen. No adverse side-effects including changes in clinical chemistry were observed. In conclusion, single injections of 600 mg TB in hypogonadal patients show favorable pharmacokinetics and pharmacodynamics. This new long-acting T ester is a promising new agent for substitution therapy of male hypogonadism and for male contraception. PMID- 1430082 TI - Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia. AB - We have demonstrated the presence of anti-PRL autoantibody in 5 patients with idiopathic hyperprolactinemia. The clinical features were suggestive of a weak biological activity of PRL, such as regular menses and no galactorrhea. Total PRL levels were markedly elevated (685 +/- 386 micrograms/L) (mean +/- SD) and the proportion of the bound form was 90.7 +/- 7.1%. Scatchard analysis revealed a low affinity, high-capacity antibody: the association constant was 0.73 +/- 0.56 x 10(7) mol-1 and the maximal binding capacity was 2139 +/- 1792 micrograms/L. Gel filtration study showed that a substantial amount of PRL (64.6 +/- 19.5%) was eluted at the position of 150,000-170,000 mol wt PRL (big-big PRL). Immunoprecipitation study using the chain-specific antibodies showed that the anti-PRL autoantibody belonged to kappa-type immunoglobulin G. These results may indicate that there exists autoantibody-related hyperprolactinemia, especially in those with particularly high serum PRL levels, who had previously been diagnosed as "idiopathic" hyperprolactinemia. PMID- 1430083 TI - Synthesis and release of endothelin-1 by human decidual cells. AB - We have studied whether a novel vasoconstrictor, endothelin-1 (ET-1), is synthesized by and released from human decidual cells in early pregnancy, and whether ET-1 acts directly on their own cells. It was observed that ET-1-like immunoreactivity (ET-1-LI) was released from cultured decidual, but not villous, cells, as a function of time. Reverse-phase high-pressure liquid chromatography of the conditioned media from the decidual cells revealed a major peak of ET-1-LI coeluting with standard ET-1. Phorbol myristate acetate, a protein kinase C activator, dose-dependently increased the release of ET-1-LI from the decidual cells, while a protein kinase C inhibitor, H7, significantly attenuated the stimulatory effect of phorbol myristate acetate on ET-1-LI release. Northern blot analysis demonstrated the expression of messenger RNA for prepro-ET-1 in the decidual tissue, but no such messenger RNA was observed in the villous tissue. The human decidual tissue contained a noninteracting, single class of binding sites demonstrating higher affinity for ET-1 and ET-2 than ET-3. This would be most consistent with the ETA receptor subtype. An ET-1-induced, dose-dependent accumulation of total inositol phosphates was also observed in human decidual cells prelabeled with myo-[3H]inositol. The present results demonstrate for the first time that human decidual cells in early pregnancy can synthesize and release ET-1. These cells also possess specific functional receptors for ET-1 which are coupled to phosphoinositide hydrolysis. Thus our data suggest a possible role for ET-1 in autocrine and/or paracrine function in human decidual cells. PMID- 1430084 TI - Growth hormone (GH)-binding protein regulation by estrogen, progesterone, and gonadotropins in human: the effect of ovulation induction with menopausal gonadotropins, GH, and gestation. AB - The recently described serum GH-binding protein (GH-BP) may reflect the GH receptor level. To assess the serum GH-BP levels under various physiological and supraphysiological levels of sex steroids, we have evaluated its concentration in 26 patients undergoing 34 cycles of ovulation induction with either human menopausal gonadotropins (hMG)/hCG or GH/hMG/hCG. The latter ovulation induction protocol was undertaken in "Clonidine negative" patients in a prospective, randomized, crossed-over manner, between GH/hMG/hCG or hMG/hCG. The increase in GH-BP levels in patients' sera undergoing ovulation induction directly correlated with peripheral estradiol (E2) (r = 0.577; P < 0.001), and with peripheral progesterone (P4) (r = 0.542; P < 0.001; n = 174) concentrations in hMG/hCG cycles, and also in GH/hMG/hCG cycles (r = 0.669, P < 0.001 for E2, and r = 0.722, P < 0.001 for P4, n = 84). GH-BP levels did not change significantly in response to 0.15 mg Clonidine ingestion. The baseline GH-BP levels significantly correlated with the body mass index of 47 patients (r = 0.547; P < 0.001). The insulin-like growth factor-I (IGF-I) concentrations increased in correlation with increasing E2 levels up to 5500 pmol/L but decreased thereafter, at very high E2 concentrations. In gestations generated by ovulation induction with hMG/hCG or GH/hMG/hCG, longitudinal measurements of GH-BP levels showed an initial sharp increase during early gestation, followed by a gradual decrease beginning around the end of the first trimester and continuing during the mid and late trimesters. In normal spontaneous pregnancies, GH-BP levels, measured from the fifth week until term, were negatively correlated with gestational age (r = -0.581; P < 0.001; n = 84). This pattern is highly suggestive of the possibility that GH-BP is coregulated not only with E2 and P4 but also with hCG, and possibly other gonadotropins as well. Indeed, in patients with "resistant ovaries", pharmacological amounts of hMG failed to increase E2 concentrations but moderately increased GH-BP levels. These data provide good indirect evidence for coregulation of the GH-BP with both sex steroids and gonadotropins. The mid and late trimesters decrease in GH-BP levels in spite of increasing sex steroids concentrations, may be attributed to the decreasing hCG concentrations, and/or to the increasing secretion of placental lactogen (PL) and placental GH with the advancing gestation. PMID- 1430085 TI - Effects of unopposed conjugated equine estrogen on lipoprotein composition and apolipoprotein-E distribution. AB - Administration of conjugated equine estrogen to 31 postmenopausal women for 3 months produced 14.6% and 9.4% decreases in low density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (apoB), and 11.5%, 12.7%, and 9.6% increases in high density lipoprotein cholesterol (HDL-C), apoA-I and apoA-II, respectively. Phospholipids of HDL2 and HDL3 were increased 57.9% and 19.3%, respectively, while relatively small increases in cholesterol of the two subfractions were not significant. Compositions of LDL and HDL and its subfractions were altered substantially with estrogen treatment. The proportion of LDL triglyceride to LDL C was increased. The phospholipid content in both the HDL2 and HDL3 subfractions (compared to cholesterol) was increased significantly (34.8% and 10.7%, respectively), while the triglyceride content was increased only in the HDL2 subfraction (43.6%). Estrogen use also caused a 9.1% reduction in total apoE levels and a redistribution of apoE to the very low density lipoprotein (VLDL) from the LDL plus HDL fraction, resulting in a significant 19.5% decrease in apoE in the LDL plus HDL fraction. Changes in apoE in the VLDL fraction were associated positively with changes in the cholesterol levels of the VLDL fraction and inversely with changes in LDL-C and apoB levels, while changes in apoE in the LDL plus HDL fraction were associated positively with changes in the levels of HDL-C. Thus, estrogen causes alterations in lipoproteins that could potentially affect their metabolism and/or function. PMID- 1430086 TI - Sustained improvement in growth velocity and recovery from suboptimal growth hormone (GH) secretion after treatment with human pituitary GH-releasing hormone (1-44)-NH2. AB - The sustained effect of human pancreatic GH-releasing hormone [hpGHRH-(1-44)-NH2] on growth rate and GH secretory patterns was studied in 14 patients (10 males and 4 females; aged 10-16 yr; all Tanner stage I or II). Nine children had inadequate spontaneous GH secretion (ISGHS), while 5 had classic GH deficiency. Seven of 9 patients with ISGHS and 1 of 5 patients with GH deficiency were given 2 sc injections/day of 5 micrograms/kg GHRH for 2-3 months; the others received 5 pulses of GHRH (5 micrograms/kg BW.pulse) for 6 nights a week for 2-13 months, given every 3 h. Six of the nine ISGHS patients increased their growth velocity in response to GHRH therapy. These same six patients maintained an increased growth velocity for up to 24 months after GHRH was discontinued. The remaining three ISGHS patients did not show a significant growth response to GHRH administration. Neither a temporary nor a sustained growth response was correlated with spontaneous overnight GH secretion in these patients. In contrast, three of five classical GH deficiency patients exhibited increased growth velocity while undergoing GHRH therapy, but growth returned to preintervention rates upon discontinuation of treatment. The other two of the five classic GH deficiency patients failed to demonstrate any growth response to GHRH treatment. The increased growth velocity that was sustained for long intervals even after discontinuation of GHRH in ISGHS patients may indicate restoration of normal regulation of the hypothalamic-pituitary GH secretion axis. PMID- 1430088 TI - Frame shift by insertion of 2 basepairs in codon 394 of CYP11B1 causes congenital adrenal hyperplasia due to steroid 11 beta-hydroxylase deficiency. AB - Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of corticosteroid biosynthesis primarily caused by a deficiency in either of two heme-containing cytochrome P450-enzymes: steroid 21- or 11 beta-hydroxylase (causing approximately 90% and 5-8% of classical CAH cases, respectively). Depending on the patient's gender, the affected enzyme, and the extent of enzymatic dysfunction, symptoms include adrenal hyperplasia, androgen excess, virilization, growth disturbance, and electrolyte imbalance. To define the molecular basis of steroid 11 beta-hydroxylase-deficient CAH, we cloned and sequenced the CYP11B1 gene (encoding 11 beta-hydroxylase) of a female patient afflicted with this disorder. Exon 7 contained a 2-basepair insertion in codon 394, leading to a reading frame shift, multiple incorrect codons, and a premature stop in codon 469, resulting in complete destruction of the enzyme's heme-binding domain. Due to parental consanguinity, this defect was homozygous and, therefore, provides a full molecular explanation for this disease. PMID- 1430087 TI - Existence of multiple peaks in plasma ethinyl estradiol and norethindrone after oral administration of a contraceptive pill. AB - Previous measurements of plasma ethinyl estradiol (EE2) and norethindrone (NE) over 24 h after oral administration of a contraceptive pill have demonstrated a single steroid peak occurring 1-2 h after pill ingestion, with a gradual decline over the next 22 h. In the present study plasma concentrations of EE2 and NE were measured 0, 0.5, 0.75, 1, 2, 4, 12, and 24 h after oral ingestion of a contraceptive pill containing 35 micrograms EE2 and 1 mg NE at 0, 3, 6, and 9 months of use in 58 normal healthy women. Contrary to previous reports, analysis of the 464 steroid curves (58 subjects x 4 time periods x 2 steroids) revealed the presence of multiple hormone peaks. Two peaks of EE2 were identified in 44.8% of women during the first pill cycle and in 75.9%, 55.2%, and 67.2% of women after 3, 6, and 9 months of pill use. Two hormone peaks of NE were observed in 29.3% of women during the first cycle and in 36.2%, 50%, and 44.8% at 3, 6, and 9 months, respectively. Existence of these multiple peaks at the frequency observed has not previously been reported. Further quantification of the frequency and magnitude of these peaks could be helpful in explaining differences in biological responses associated with pill use. PMID- 1430090 TI - Screening for Y-derived sex determining gene SRY in 40 patients with Turner syndrome. AB - In Turner patients, the presence of a Y chromosome or derivative Y is correlated with the risk of gonadoblastoma induction. "Marker" chromosomes originating from Y, may not show characteristic fluorescence and then be very difficult to identify by conventional cytogenetic techniques, although they still predispose the patients to gonadal tumors. Using polymerase chain reaction of the gene from the sex-determining region of the Y chromosome, we screened 40 Turner patients (thirty seven 45X and three 45X,46XX) for the presence of Y chromosomal DNA. We were able to identify karyotypically unrecognized Y chromosome material in 1 patient out of the 40 studied. In this patient mild clinical and biological hyperandrogenism was observed. Reliability of our technique was ascertained by the detection of the expected 648 base pairs amplified DNA fragment in all normal male controls as well as in 3 Turner patients with confirmed 45X,46XY mosaicism. Despite the low frequency of unrecognized Y chromosome material (1 case over 40 in our experience), our data suggest that polymerase chain reaction of the gene from the sex-determining region of the Y chromosome is worthy of being performed in Turner patients considering the potential risk of the presence of a Y chromosome. PMID- 1430089 TI - The effects of human proinsulin on glucose turnover and intermediary metabolism in insulin-dependent-diabetes mellitus. AB - We have compared the action of human proinsulin and insulin on glucose turnover, intermediary carbohydrate, and lipid metabolism in insulin-dependent-diabetic (IDDM) subjects. Six, young, weight-matched (23 +/- 2 kg-2) IDDM subjects underwent separate hyperinsulinemic euglycemic clamps. Three, low dose, iv infusions of both insulin and proinsulin were used to construct dose response curves. The proinsulin infusions were chosen to give steady state levels approximately or equal to 20-fold higher on a molar basis than insulin, based on previous findings that proinsulin has only 5-10% the biological potency of insulin. Hepatic glucose production, measured using [6'6'2H2]glucose, was suppressed equally by proinsulin and insulin at the three dose levels; (I1) 2.8 +/- 0.7 (P1) 3.3 +/- 0.6, (I2) 2.3 +/- 0.9 (P2) 3.3 +/- 1.1, (I3) -2.0 +/- 1.7 (P3) -1.1 +/- 0.6 mumol/kg min-1. Percentage elevation of glucose disposal was significantly increased during the insulin infusions compared to proinsulin; (I1) 132 +/- 12 (P1) 78 +/- 4 p < 0.01; (I2) 157 +/- 18 (P2) 104 +/- 14; P < 0.05; (I3) 242 +/- 23 (P3) 159 +/- 24 p = 0.02. Dose response curve analysis demonstrated that proinsulin stimulated glucose disposal approximately or equal to 3.7% whereas suppression of HGP was congruent to 5.7% compared to insulin. Proinsulin had a significantly weaker effect than insulin, at the lowest infusion dose, in percent suppression of plasma nonesterified fatty acids (I1 34 +/- 4, P1 14 +/- 15%; P < 0.05), blood glycerol (I1 47 +/- 4, P1 30 +/- 3%; P < 0.01) and 3 hydroxybutyrate levels (I1 81 +/- 7, P1 42 +/- 17%; P < 0.05). Proinsulin caused significant net reductions in blood lactate levels compared to insulin at each infusion dose; (P1) -130 +/- 34, (I1) -32 +/- 30 mumol/L (P < 0.05) (P2) -139 +/- 76 (I2) +8 +/- 65 mumol/L (P < 0.05) (P3) 48 +/- 60 (I3) 230 +/- 64 mumol/L (P < 0.05). We conclude that in IDDM: 1) proinsulin has a preferential effect on the liver compared to muscle, in terms of glucose handling; 2) proinsulin may have a different effect on lactate metabolism compared to insulin; 3) proinsulin at the lowest dose resulted in an inability to suppress lipolysis and ketogenesis; 4) glucose turnover can be underestimated using [6'6'2H2]glucose. PMID- 1430091 TI - Effect of physiological hyperinsulinemia on counterregulatory hormone responses during hypoglycemia in humans. AB - We evaluated the effect of continuous physiological hyperinsulinemia on counterregulatory hormone responses in seven healthy subjects, each studied on two occasions. Hormone responses were measured during identical 2-h periods of hypoglycemia (plasma glucose target 3.5 mmol/L) at insulin levels of 350 pmol/L or 640 pmol/L. During hypoglycemia, there were significant (50-1400%) increases in glucagon, epinephrine, norepinephrine, GH, and cortisol which were comparable in the two groups. We further evaluated the influence of the duration of mild hyperinsulinemia on the responses in an additional group of normal subjects (n = 7). Brief (30 min) exposure to insulin was compared to a prolonged (3.5 h) insulin infusion, each followed by identical hypoglycemia. Plasma insulin (approximately 350 pmol/L) and plasma glucose (target 3.3 mmol/L) were similar in both groups. The increases in epinephrine, norepinephrine, GH, and cortisol during hypoglycemia were virtually identical in the two groups. However, the secretion of glucagon was blunted following prolonged hyperinsulinemia, increasing to levels of 249 +/- 17 ng/L in the brief studies and to only 185 +/- 20 ng/L in the prolonged studies (P < 0.005). The insulin-induced decrement in plasma amino acids were similar in the two studies and could not account for the impaired glucagon secretory response. CONCLUSIONS: 1) Brief exposure to even high physiological levels of insulin do not alter the magnitude of counterregulatory hormone secretion during hypoglycemia; 2) prolonged hyperinsulinemia results in a selective blunting of the plasma glucagon response to hypoglycemia, perhaps due to a direct suppressive effect of insulin on alpha-cell secretion. PMID- 1430092 TI - Serum growth hormone (GH)-binding protein and insulin-like growth factor-I levels in Turner's syndrome before and during treatment with recombinant human GH and ethinyl estradiol. AB - Serum levels of GH-binding protein (GH-BP) and insulin-like growth factor-I (IGF I) were measured in 14 adolescent girls with Turner's syndrome (TS) before and during treatment with recombinant human GH (rhGH) and oral ethinyl estradiol (EE2). Before treatment, the mean +/- SE GH-BP level in TS patients was 33.2 +/- 2.0%; this was higher (P < 0.05) than that in bone age-matched (27.9 +/- 1.1%; n = 13) or chronological age-matched (28.1 +/- 0.8%; n = 17) control girls. The mean +/- SE IGF-I level in TS girls (283 +/- 26 micrograms/L) was comparable to that in bone age-matched controls (255 +/- 17 micrograms/L), but lower (P < 0.005) than that in chronological age-matched pubertal controls (568 +/- 35 micrograms/L). In 7 TS girls treated with daily sc injections of rhGH in a dose of 0.8 U/kg.week for 18 months, serum levels of IGF-I increased from 330 +/- 39 to 707 +/- 48 micrograms/L after 3 months of treatment and remained elevated for the entire observation period (P < 0.002). In contrast, GH-BP levels did not change significantly. In 7 other TS girls, puberty was induced after 2 yr of daily sc injections with rhGH (1 U/kg.week) by adding 100 ng/kg.day EE2, orally, during ongoing rhGH therapy. During 18 months of pubertal induction, serum GH-BP levels increased gradually from 31.4 +/- 2.7% at the start of EE2 treatment to a maximum of 49.2 +/- 0.8% after 1 yr (P < 0.001). Serum IGF-I levels, in contrast, did not change significantly. These results show that in adolescent TS patients 1) pretreatment serum GH-BP levels are higher than in bone age-matched or chronological age-matched control girls, and IGF-I levels are similar to those in bone age-matched but lower than those in chronological age-matched controls; 2) during rhGH treatment GH-BP levels do not change, whereas IGF-I levels increase significantly; and 3) oral EE2 treatment during ongoing rhGH treatment increases GH-BP levels markedly, but does not modify IGF-I levels. PMID- 1430093 TI - Clinically nonfunctioning pituitary adenoma and octreotide response to long term high dose treatment, and studies in vitro. AB - We have studied seven patients with a clinically nonfunctioning or alpha-subunit secreting pituitary macroadenoma, four of whom received long term, high dose octreotide treatment. We have attempted to correlate the presence of somatostatin receptors (SS-R) in the adenomas and the outcome of octreotide treatment, as measured by tumor size, improvements in visual field defects, and hormonal response. The presence of SS-R in the pituitary adenomas was demonstrated in vivo using [111indium]octreotide scintigraphy and in vitro by autoradiography of tissue fragments obtained after transsphenoidal surgery. Adenomas from six of the seven subjects were SS-R positive. High dose (1200 micrograms, sc, daily) octreotide treatment was given to four subjects, three of whom were SS-R positive. Improvement of the visual field defects was observed in three of four patients (including the SS-R-negative subject), although no computed tomographic scan-assessed tumor size reduction was found. Two of four patients showed small but significant reductions in serum FSH concentrations (to 83% and 93% of initial values) with treatment. These in vivo responses to high dose octreotide treatment could not be predicted by pretreatment responses to 200 micrograms TRH or 100 micrograms octreotide. Tissue fragments for cell culture were obtained from six patients, and in vitro release of gonadotropins and/or alpha-subunit could be demonstrated in five cultures. In vitro, octreotide (10 nmol/L) significantly decreased gonadotropiin or subunit release in three of five cultures, whereas bromocriptine (10 nmol/L) significantly reduced the release in four of five cultures and to a significantly greater extent than octreotide. In conclusion, in six of seven patients with a clinically nonfunctioning or alpha-subunit-secreting pituitary adenoma, SS-R were demonstrated in the tumor. In vitro incubation of adenoma cells with octreotide resulted in mild inhibition of gonadotropin or alpha-subunit release. Although in vivo long term treatment with high doses of octreotide did not result in substantial tumor size reduction, improvement of visual field defects was observed in three of four subjects. PMID- 1430094 TI - Suppression of human spermatogenesis by testosterone implants. AB - Hormonally induced azoospermia is an effective, reversible form of male contraception; however, some men treated with weekly im testosterone enanthate (TE) injections fail to become azoospermic. As weekly injections cause widely fluctuating and supraphysiological testosterone levels, we tested the hypothesis that more stable, physiological testosterone levels would consistently produce azoospermia. Using a depot testosterone formulation which provides stable, physiological range testosterone levels for up to 6 months, we studied nine men before and after insertion of six 200 mg testosterone implants under the abdominal wall skin and compared the results with 38 men treated in a previous study with weekly im injections of 200 mg TE. Testosterone implants suppressed sperm output to near-azoospermia between the second to fourth postimplant months returning to normal by the sixth postimplant month. The fall in sperm output at the first month was greater after testosterone implants than TE injections (58% vs. 17%, P = 0.011) but similar proportions of men became azoospermic (5/9 vs. 25/38) or severely oligozoospermic (< 1 million/ml; 9/9 vs. 37/38). Plasma testosterone and estradiol levels remained mostly within the eugonadal range after implants but were markedly supraphysiological during TE injections. Both treatments suppressed immunoreactive LH and FSH to undetectable levels by ultrasensitive fluoroimmunoassay. Sex hormone-binding globulin levels were decreased and PRL levels increased by TE injections but neither was changed by testosterone implants. Prostate-specific antigen demonstrated a small rise of marginal significance (P = 0.065) after testosterone implants. Fewer men experienced acne after implants (0/9 vs. 25/38, p = 0.0004). Therefore a depot testosterone preparation with quasi-zero-order release demonstrates higher dose efficiency with similar (but not uniform) efficacy at inducing azoospermia but may cause fewer androgenic side-effects than weekly TE injections. PMID- 1430095 TI - The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. AB - Biochemical evidence of hyperthyroidism is frequently encountered in hyperemesis gravidarum, but its relationship to the cause of hyperemesis is unknown. We studied the relationship of serum hCG, thyroid function, and severity of vomiting among 57 hyperemesis patients and 57 controls matched for gestational age. TSH was suppressed in 60% of hyperemesis patients and 9% of controls. hCG correlated directly with free T4(r = 0.45, P < 0.001) and inversely with TSH (r = -0.48, P < 0.001). Hyperemesis patients had significantly greater mean serum hCG, free T4, total T3, and estradiol, and lesser serum TSH compared to controls. Hyperemesis patients with suppressed TSH had significantly greater free T4 and hCG compared to those with TSH in the normal range. Control and hyperemesis subjects were divided into four groups based on the severity of vomiting. The degree of biochemical hyperthyroidism and hCG concentration varied directly with the severity of vomiting. Unextracted serum was tested for thyrotropic activity by measuring its effect on iodide uptake in cultured FRTL-5 rat thyroid cells. Thyrotropic activity correlated with serum hCG (r = 0.50, P < 0.001). These data show that biochemical hyperthyroidism is a common finding in patients with hyperemesis gravidarum and suggest that hCG is the thyroid stimulator in this state. The increased estradiol concentration in patients with hyperemesis gravidarum may be attributed to the effects of hCG on steroidogenesis. PMID- 1430096 TI - Immunoradiometric analysis of circulating human glycosylated and nonglycosylated prolactin forms: spontaneous and stimulated secretions. AB - The monoclonal antibodies (MAbs) obtained in mice immunized with human PRL coupled to an anti-PRL MAb were screened for their ability to distinguish the glycosylated (G-) and nonglycosylated (NG-) forms of PRL. The 431-29 MAb exhibited high affinity binding for NG-PRL but little or no cross-reactivity to G PRL. Using this antibody in conjunction with other MAbs which equally recognized both forms, we developed 2 immunoradiometric assays which were used to determine the amount of G- and NG-PRL in plasma. In 85 normal subjects, NG-PRL baseline levels averaged 6.6 +/- 3 micrograms/L, and represented 76 +/- 8% of the total PRL immunoreactivity. In 74 pregnant women, this proportion was significantly higher during the last 2 trimesters (84 +/- 4% and 85 +/- 6%), as compared to the first trimester (76 +/- 7%). In 6 healthy volunteers studied over 24 h, 79% of the NG-PRL peaks detected using the cluster algorithm occurred concomitantly to a G-PRL peak. The mean NG-PRL/PRL ratio was significantly higher during NG-PRL pulses (81 +/- 9%) than during valleys (71 +/- 12%). Similarly, this ratio was significantly increased during TRH or metoclopramide stimulated PRL secretion (to 88 +/- 7% and 86 +/- 6%, respectively). We conclude that 1) NG-PRL is the predominant immunoassayable form of PRL in plasma; 2) both G- and NG-PRL are cosecreted but NG-PRL is the main PRL form released during spontaneous or pharmacologically induced PRL secretion. PMID- 1430097 TI - Regulation of immunoreactive inhibin patterns in baboon pregnancy: maternal, placental, and fetal considerations. AB - To better understand the sources and regulation of circulating inhibin during primate pregnancy, immunoreactive inhibin was measured in sera obtained from the maternal saphenous vein, uterine vein, and the fetus at varying times of baboon pregnancy. In both intact and fetectomized (fetus removed on day 100 of gestation; term = 184 days) animals, maternal serum inhibin concentrations were relatively constant between day 80 (first sampling day) and day 110 of gestation, after which they then steadily increased until days 155-165 (end of sampling). The increase in inhibin concentrations was significantly less in the fetectomized animals than in the intact baboons. Restoration of estrogen levels in the fetectomized animals did not significantly alter the circulating inhibin concentrations. Similarly, administration of the estrogen antagonist MER-25 to intact animals in the last trimester had no effect on maternal serum inhibin concentrations. Inhibin concentrations in uterine venous blood collected on day 100 of gestation were not significantly different from those in the maternal saphenous vein. However, the inhibin concentrations of uterine venous blood collected late in gestation (days 155-165) in either intact or fetectomized animals were significantly higher than the corresponding maternal venous concentrations, suggesting that the uteroplacental tissue becomes a source of circulating inhibin during the third trimester of pregnancy. Consistent with this suggestion was the detection of inhibin alpha-subunit mRNA in the placentae of intact or fetectomized animals obtained late in pregnancy, but its absence at midgestation. Immunoreactive inhibin concentrations were about 16 times higher (6500 +/- 831 mu Leq/mL) in fetal blood than in maternal blood (411 +/- 23 mu Leq/mL) at midgestation. The fetal blood concentrations significantly decreased to about 2800 mu Leq/mL by days 160-165 of gestation, but were still greater than those in the mother (approximately 1000 mu Leq/mL). The umbilical arterial and venous concentrations were the same as the fetal blood concentration of inhibin. The role of the baboon fetal adrenal in inhibin production was studied. Fetal adrenals collected from days 59, 135, and 167 of gestation contained the mRNA for the inhibin alpha-subunit in relatively high abundance. The in utero administration of ACTH for 30 min to five fetuses at midgestation (days 100-110) apparently did not alter the fetal concentration of immunoreactive inhibin. In summary, maternal serum inhibin levels increase during the last trimester of baboon pregnancy. This is suggested to be due to an increasing contribution of placental inhibin secretion, which is regulated not by placental estrogen production but, perhaps, by placental growth.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1430098 TI - Gestational age-dependent dual action of epidermal growth factor on human placenta early in gestation. AB - In order to better understand the role of epidermal growth factor (EGF) in the regulation of placental growth and function, effects of EGF on proliferative activity and differentiated function of trophoblast were examined. Explants from very early (4-5 week) placentas and early (6-7 week, 8-9 week, 10-12 week) placentas were respectively cultured under a serum-free condition in the absence or presence of EGF (100 micrograms/L) for the first 48 h, and the cultures were continued for subsequent 72 h without EGF. The proliferative potential and differentiated function of trophoblast were assessed by immunohistochemical Ki-67 staining and by determining the ability to secrete human CG (hCG) and human placental lactogen (hPL), respectively. Quantitative estimates of proliferative activity based on mean percentage of Ki-67 positive nuclei showed that EGF stimulated proliferative potential of cytotrophoblast in very early (4-5 week) placental explants. The EGF stimulation of trophoblast proliferation was apparent at a 12-h EGF-treated period. By contrast, early (6-12 week) placental explants did not respond to EGF with increase in trophoblast proliferation. Instead, in early placental explant culture EGF stimulated hCG and hPL secretion with a lag period of 72 h, whereas very early placental explants did not respond to EGF with increase in hCG and hPL secretion. These results suggest that EGF exerts gestational age-dependent dual action on the first-trimester placenta: one is to stimulate trophoblast proliferation in 4-5 week placenta and the other is to stimulate differentiated trophoblast function in 6-12 week placenta. PMID- 1430099 TI - Demonstration and localization of growth hormone receptor in human skin and skin fibroblasts. AB - Clinical evidence suggests that skin is responsive to GH status in vivo. We sought to demonstrate the presence of GH receptors in human skin and in cultured skin fibroblasts using the techniques of immunohistochemistry and northern blotting. Human foreskin was obtained at surgery for preparation of sections and primary fibroblast cultures. Skin sections and fibroblast monolayers were immunostained using a monoclonal antibody which recognizes the hGH receptor (MAb 263). Positive immunoperoxidase staining was seen in all epidermal layers except the stratum corneum, in dermal sweat and sebaceous glands, and in dermal fibroblasts. In cultured fibroblasts capping of surface GH receptor was observed after aqueous formaldehyde fixation, whereas fixation in Carnoy's solution resulted in granular cytoplasmic staining. Fibroblast poly A+ RNA was prepared from cultured skin fibroblasts, separated by denaturing agarose gel electrophoresis, blotted onto nitrocellulose, and hybridized to a 32P-labeled, 847 base pair (bp) hGH receptor complementary DNA (cDNA) clone. Human liver and non-pregnant rabbit liver total RNA were used as controls. Fibroblast poly A+ RNA contained a single hybridizing species of approximately 5.2 kilobase. Human liver total RNA also contained a single hybridizing species of 4.9 kilobase. We have demonstrated the presence of GH receptor protein in human skin and growth hormone receptor mRNA and protein in cultured human skin fibroblasts. These observations suggest that GH may indeed have a direct role in modulating keratinocyte and fibroblast function. PMID- 1430100 TI - Localization of renin gene expression to monkey ovarian theca cells by in situ hybridization. AB - To investigate the sites of renin gene expression and localization of renin in primate ovaries, five cynomolgus (Macaca fascicularis) and one rhesus (Macaca mulatta) monkey were treated with gonadotropins to induce multiple follicle development. One ovary was removed before hCG injection (1200 IU) from three monkeys and one ovary was removed 36 h after hCG administration from three monkeys. In three monkeys, the remaining ovary was removed 3, 5, and 7 days after injection of hCG. To detect and localize renin messenger RNA, 35S-radiolabelled 1.1 kb length complementary DNA and RNA probes of human renin were used for in situ hybridization. To compare the synthesis with the presence and the storage of renin or prorenin, renin antigen was assessed by immunohistochemistry in the same tissues using a polyclonal antibody against human renin (R15). Renin mRNA was detected by in situ hybridization only in ovaries collected within 5 days of exposure to hCG. All such ovaries exhibited a positive signal. Renin mRNA was localized to the theca interna and theca lutein cells. Positive cells were observed in a few growing antral follicles, in occasional mature preovulatory follicles, in corpus luteum, and most strikingly in atretic follicles. No signal was detected in primordial, primary, or in small antral follicles of ovaries exposed to hCG. In contrast with the in situ hybridization data, no signal was detected by immunohistochemistry using antirenin antibodies which exhibited a positive signal in monkey kidney. These results indicate that hCG turns on renin gene expression. Renin is synthesized without significant intracellular storage in monkey ovarian theca interna cells and in corpus luteum. The absence of storage of renin is consistent with the high concentrations of prorenin found in ovarian follicular fluid of hCG stimulated primates and with our knowledge of cellular renin processing which indicate that prorenin is secreted constitutively as it is synthesized. PMID- 1430101 TI - In memoriam Gerald D. Aurbach. PMID- 1430102 TI - Polyvalent immunoglobulin for intravenous use interferes with cell proliferation in vitro. AB - Intravenous immunoglobulin is used to an increasing extent in various immune mediated diseases, but its mechanism(s) of action in vivo is incompletely understood. Previous studies have shown that intravenous immunoglobulin may interfere with autoantibodies and their production by B cells and also inhibit Fc mediated antibody-dependent cytotoxicity. Here we describe a novel effect of intravenous immunoglobulin on proliferation of in vitro activated peripheral blood lymphocytes and autonomously growing cell lines of various origin. Independently of whether proliferation was autonomous or induced by antigen specific or antigen-nonspecific reagents, proliferation was inhibited in a dose dependent fashion, as measured by reduced 3H-thymidine and BrdU uptake and cell counting. The effect was not due to cytotoxic effects of intravenous immunoglobulin and was reversible after removing the intravenous immunoglobulin by washing. The IgG levels required for this inhibition of proliferation are supraphysiological but are reached in vivo during treatment with intravenous immunoglobulin. PMID- 1430103 TI - An immunodominant haptenic epitope of carbamazepine detected in serum from patients given long-term treatment with carbamazepine without allergic reaction. AB - An anticarbamazepine antibody was detected in the serum of a patient with severe carbamazepine-induced serum sickness. We found that the patient's T cells and IgG antibody recognized an epitope which appeared in subjects showing an allergic reaction, as well as that in subjects who showed no allergic reaction, after long term carbamazepine therapy. These results show that an anti-carbamazepine immune response does not occur in the majority of subjects who undergo long-term carbamazepine therapy without developing allergic symptoms, although the immunodominant haptenic epitope of carbamazepine is present in their sera. PMID- 1430104 TI - The influence of aging on the induction and manifestations of experimental systemic lupus erythematosus. AB - The influence of age on autoimmunity was studied in a model in which experimental systemic lupus erythematosus (SLE) is induced in normal mice by the injection of a human monoclonal anti-DNA antibody expressing a common idiotype designated 16/6 Id. The resulting disease is expressed by the production of a variety of autoantibodies and clinical manifestations characteristic to human SLE. Female BALB/c mice, at ages of 2 and 12 months, were immunized with the 16/6 Id. Mice were tested periodically for the presence of autoantibodies. The production of all autoantibodies tested was significantly lower in the older mice as compared to the group of young mice. Clinical manifestations which included leukopenia, increased erythrocyte sedimentation rate and proteinuria were similar in both age groups. Kidney evaluations revealed differences among the two groups of mice. While in all kidney sections of young mice multiple immune complex deposits were detected, in the group of older mice half had similar pathology while the rest either were negative or had only segmental and partial glomerular immune complex depositions. Thus, aging is associated with a decrease in the capacity to respond to the pathogenic anti-DNA, 16/6 Id, by the production of antibodies and autoantibodies and in the expression of a milder disease. PMID- 1430105 TI - Effects of alpha-interferon on gamma-interferon production of peripheral blood mononuclear cells in hepatitis B virus carriers. AB - We studied gamma-interferon production of phytohemagglutinin-stimulated peripheral blood mononuclear cells in response to alpha-interferon in hepatitis B virus carriers and healthy individuals. The magnitude of gamma-interferon production was significantly higher in patients with anti-HBe antibody than in patients with HBe antigen and healthy individuals. Furthermore, alpha-interferon augmented the production of gamma-interferon of peripheral blood mononuclear cells from patients with active liver injury [serum alanine aminotransferase (ALT), greater than 40 U/L], but not that from patients with inactive liver injury (serum ALT, less than 40 U/L) or healthy individuals. These results suggested that alpha-interferon could enhance the cellular immune response against hepatitis B virus by augmenting the endogenous production of gamma interferon in patients with active liver injury, implying that the responsiveness to alpha-interferon might be responsible for liver cell injury. PMID- 1430106 TI - Disease severity in rheumatoid arthritis: relationships of plasma tumor necrosis factor-alpha, soluble interleukin 2-receptor, soluble CD4/CD8 ratio, neopterin, and fibrin D-dimer to traditional severity and functional measures. AB - Rheumatoid arthritis is a complex inflammatory disease of unknown cause. Although various laboratory and clinical measurements are useful in managing these patients, there is a need for better tests to quantitatively assess disease activity. The purpose of this study was to investigate the association of certain immune and inflammation (I-I) parameters with four traditional disease severity measures and a functional measure in rheumatoid arthritis patients. A single set of patient blood samples was analyzed, and four traditional disease severity measures and patient functional statuses were determined from 64 consecutive outpatients with rheumatoid arthritis. Plasma tumor necrosis factor-alpha (TNF), soluble interleukin-2 receptor (sIL-2R), sCD4 and sCD8 (and the sCD4/sCD8 ratio), neopterin, and fibrin D-dimer were analyzed in relationship to Westergren erythrocyte sedimentation rate (ESR), physician assessment of disease activity, joint pain count, grip strength, and Arthritis Impact Measurement Scale (AIMS) scores. Rheumatoid arthritis patients had higher mean levels of all I-I measures (except sCD4) compared to healthy subjects. Initial significant correlations between TNF, sIL-2R, and D-dimer and several disease severity and functional measures were detected. When we controlled for the covariates age, gender, race, and medications, regression analyses indicated that, as a group, the I-I measures were significantly related to grip strength, physician disease severity rating, ESR, and total joint pain. When the predictive values of the I-I measures were tested controlling for the covariates and ESR, D-dimer was independently and significantly associated with variability in grip strength, physician disease severity, and AIMS physical disability, while TNF was associated with a significant amount of variability in total joint pain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430107 TI - Cold-dependent activation of complement: recognition, assessment, and mechanism. AB - Cold-dependent activation of complement (CDAC) is a phenomenon characterized by low hemolytic complement activity in chilled serum. Complement component levels are normal when measured immunologically, and there is normal hemolytic activity in EDTA plasma or serum maintained at 37 degrees C. Little attention has been paid to CDAC except in Japan, and current unfamiliarity with it, even by clinical immunologists, can lead to confusion and unnecessary laboratory tests. A 66-year old patient with a complex medical history is described whose complement tests showed abnormalities characteristic of CDAC. Evidence for classical complement pathway activation in the cold was obtained by CH50 measurements, by hemolytic C4 determinations, by C4a, C3a, and C4d generation, and by quantitating C1s-C1r-(C1 inhibitor)2 complexes. A good correlation was observed among these parameters. Cryoprecipitates were absent. CDAC activity has persisted for over 5 years and is greater at 13 than at 4 degrees C. Activation is ablated by heating at 56 degrees C and restored by the addition of C1 to the heated serum. Adsorption by streptococcal protein G-Sepharose and precipitation by 2.5% polyethylene glycol support the hypothesis that CDAC is caused by aggregated IgG. The CDAC factor(s) also induces complement activation in normal serum but has not interfered with Raji cell or C1q binding tests or with FACS analysis. More limited studies of a second individual experiencing CDAC yielded similar results. PMID- 1430109 TI - [Diagnosis of vertigo]. PMID- 1430108 TI - Expression of a functional p75 interleukin-2 receptor on lung lymphocytes from patients with human immunodeficiency virus type 1 (HIV-1) infection. AB - Lung involvement in patients affected by HIV-1 infection is characterized by an alveolitis sustained by the accumulation of CD8+ T lymphocytes. To investigate whether in situ T cell growth plays a relevant role in the pooling of CD8+ lymphocytes, we have analyzed the activity of two lymphokines involved in the mechanisms of T cell proliferation, i.e., interleukin-2 (IL-2) and interleukin-4. To this aim, following appropriate triggering and blocking, the expression and the functional role of IL-2 receptors (IL-2R) (both p55 and p75 chains) and IL-4 receptors have been analyzed on T lymphocytes obtained from the bronchoalveolar lavage (BAL) of 16 HIV-1+ patients. Molecular and phenotypic studies we performed demonstrated that CD8+ lymphocytes from the BAL of HIV-1 + patients strongly expressed the p75 chain of IL-2 receptor, while neither p55 mRNA nor its surface membrane product (Tac antigen) was detectable; in addition, there was no expression of IL-4 receptors. IL-2 stimulation was able to induce T cell growth in a dose-dependent manner, whereas IL-4 did not. Finally, using mAbs which specifically block the p55 or p75 IL-2R, we showed that both subunits of IL-2R were involved in the proliferative activity of lung lymphocytes. The results obtained in the present study directly demonstrate that BAL T lymphocytes of HIV 1 + patients express a fully functional IL-2 receptor apparatus, pointing to the role for this lymphokine in maintaining the alveolitis taking place in the lungs of AIDS patients. PMID- 1430110 TI - [The clinical application of rotational stereo digital angiography to the field of neurosurgery]. AB - A new system for 3-dimensional angiography, named "Rotational stereo digital angiography" (RSDA), was applied to 36 patients with neurosurgical lesions. This system consists of a new rotating X-ray apparatus and a digital processor, and accumulates 144 projectional images in 2.2 seconds during a 180 degree transverse rotation of the X-ray device. These images are digitally processed and displayed on two CRT's at 5 different degrees so that a rotating image of the angiogram is observed. Thirteen cerebral aneurysms, 16 brain and skull tumors, and 7 other neurosurgical lesions were examined with this system and compared with conventional angiography. The aneurysms were examined to 1) identify the aneurysm, 2) demonstrate the shape of the aneurysm, 3) demonstrate the aneurysmal neck, and 4) illustrate the relationship between the aneurysm and the mother vessels. The tumors were examined to 1) demonstrate the tumor stain, 2) identify the feeding arteries, 3) identify the draining veins, and 4) illustrate the relationship between the lesion and the major vessels. Similarly, 1) demonstration of the lesion, and 2) illustration of the relationship between the lesion and the major vessels were examined for other lesions. The findings in RSDA and conventional angiography were classified into -, +/-, +, or +2 with regard to the readiness to the aspects described above. They were then statistically compared. According to the statistic analysis, RSDA is significantly more illustrative for aneurysms than conventional angiography. For tumors and for other lesions, there was no significant difference between RSDA and conventional angiography. These results indicate the usefulness of RDSA in the field of neurosurgery. PMID- 1430111 TI - Effect of exposure to benzene on natural killer (NK) cell activity and interleukin-2 (IL-2) production of C57BL/6 mice. AB - To investigate the effect of benzene on murine splenic natural killer (NK) cell activity and interleukin-2 (IL-2) production, we exposed C57 BL/6 mice to benzene for 28 days. Benzene exposure via drinking water at doses of 27 and 154 mg/kg/day yielded the following results. 1) A decrease of spleen cell number was detected on the 14th day of benzene exposure at 154 mg/kg/day, and on the 21st and 28th day of exposure at both 27 mg/kg/day and 154 mg/kg/day. 2) NK activity per viable spleen cell was temporarily enhanced on the 21st day of exposure at doses of 27 and 154 mg/kg/day, thereafter returned to control levels. 3) IL-2 production was inhibited after 28 days of benzene exposure at 27 and 154 mg/kg/day. After ending exposure at doses of 27 mg/kg/day for 28 days, the decreased spleen cell number began to return to control levels from the 14th day on, and reduced IL-2 production returned to control levels. These results suggest that, NK cells are resistant to benzene toxicity, while IL-2 producing cells are sensitive. Thus, an imbalance in immune system was caused by toxic benzene action. PMID- 1430112 TI - [Urodynamic abnormalities in patients with lumbar diseases. With special reference to autonomic dysfunction]. AB - In order to investigate urinary dysfunction in lumbar disease from the point of view of autonomic dysfunction, urodynamic examinations and sympathetic skin responses (SSR) were evaluated in patients with lumbar diseases. Cystometry and uroflowmetry were performed as urodynamic examinations on 40 patients with lumbar diseases including intervertebral disc herniation (IDH), spinal canal stenosis (SCS), and spondylolisthesis with spondylolysis. SSR of the feet were recorded in 6 healthy men, as controls, and in 10 patients with IDH; The latencies and amplitudes of SSR were compared. Eighty percent of the patients showed some abnormality in the urodynamic examinations that indicated an occult neurogenic bladder. Also, the mean and maximal amplitudes were significantly lower in the patients with IDH than in the controls (p < 0.01). While the occurrence of a neurogenic bladder was considered to be a parasympathetic dysfunction, abnormalities in SSR were considered to be sympathetic dysfunctions. It was therefore considered that autonomic dysfunction was present in the bladder and lower extremities of patients with lumbar diseases. PMID- 1430113 TI - [Spatial and quantitative analysis of the QRS and T waves by Frank-lead orthogonal electrocardiography in normal children. Comparative study in an early and late cord-clamping groups in newborns]. AB - We studied a spatial and quantitative analysis of QRS and T waves by Frank-lead orthogonal electrocardiography (afterwards; ECG) in 50 cases of normal newborns, 30 cases of infants, 50 cases of adults, and also the variation in age was investigated. In the newborns, the comparative study was made serially, longitudinally in 21 infants with an early clamping of the cord and 29 infants with a late clamping of the cord. The results are mainly as follows. 1) The parameters reflecting the cardiac electromotive force of the right ventricle such as Sx, Qz and Sx+Qz decreased with aging. 2) Rx, i.e., the maximum leftward projection of QRS vector increased until the children, probably because the left ventricle was dominant in their growth and development and in the increased amount of work. A subsequent reduced value in the adults was considered to be mainly due to an increase of the distance between the heart and electrode by the increase in the thorax, particularly the transverse diameter and due to the growth in subcutaneous fat and muscle. 3) The values of Rx/Sx increased with aging. Rx and Sx in the adults were less than those in the children, but Rx/Sx was larger than that of Rx because Sx was less than Rx. 4) Age-related changes of Tz was most characteristic and was negative up to several days after birth. T vector was in forward direction and then turned positive (in backward). This was greatest at the period of the infants. Subsequently, it turned negative in the childhood, and extent was maximum in the adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430114 TI - [A study to increase the therapeutic effects of adoptive immunotherapy in vivo. Influence on the generation of lymphokine activated killer (LAK) cells and therapeutic effects of LAK cells with anti-tumor drug (cyclophosphamide)]. AB - To enhance the effect of adoptive immunotherapy (AIT), we investigated the induction and characteristics of lymphokine activated killer (LAK) cells and also analyzed the combined effects of AIT with an antitumor drug (cyclophosphamide: CPA) in mice models. LAK cells were generated from C57/BL/6 (B6) spleen cells. The spleen cells were passed through a nylon wool column and cultured in RPMI 1640 medium containing 10% FCS and 2 x 10(3) units of human recombinant IL-2 (hr IL-2) for up to 14 days. During this period, the time kinetic analyses of the LAK cells' cytotoxicity and motility were performed. The cytotoxicities against Lewis Lung Carcinoma (3LL), evaluated by standard 51Cr release assay, gradually increased during the cultured period, and the motilities, determined by a modified version of the Boyden chamber method, greatly increased within the first 7 days' incubation. Based on these in vitro findings, we examined the efficacy of AIT alone or in combination with chemotherapy (CPA) in in vivo studies. AIT was performed in the following way: LAK cells were intravenously infused and rIL-2 was intraperitoneally administered for 5 consecutive days following LAK cell administration. CPA was intraperitoneally administered. The therapy protocols were as follows. There were seven experimental groups. Group I; the mice were infused with 3-day cultured LAK cells (3DLAKs) on the second day after tumor inoculation (day 2). Group II; the mice were infused with 3DLAKs on day 5. Group III; 10-day cultured LAK cells (10DLAKs) on day 2. Group IV; 10DLAKs on day 5. Group V (AIT and CPA combination); AIT (10DLAKs) was started on day 5 followed by CPA on day 10. Group VI; CPA was performed on day 5 followed by AIT (10DLAKs) on day 10. Group VII; CPA was performed on day 5 without AIT. Each group consisted on 15 mice. The therapeutic efficacies were evaluated by calculating the median survival time of each group. The results of these experiments were as follows (mean +/- SD); Group I's median survival time was 16.8 +/- 3.2 days, Group II 15.1 +/- 2.1 days, Group III 19.2 +/- 5.4 days, Group IV 16.1 +/- 4.8 days, Group V 23 +/- 6.3 days, Group VI 32 +/- 8.4 days and Group VII 22 +/- 5.1 days. These results suggested that the efficacy of AIT is closely related to the LAK cells' cytotoxicity and motility. Although AIT alone in the advanced tumor bearing host had a limited effect, combination with CPA improved it's efficacy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1430115 TI - [Pathology of the grafted liver]. PMID- 1430116 TI - [Current status of chronic dialysis and its several complications]. PMID- 1430117 TI - The fertilization and development of mouse oocytes following cortical granule discharge in the presence of a protease inhibitor. AB - The effect of leupeptin, a serine protease inhibitor, on the fertilization and development potential of oocytes stimulated to undergo cortical granule exocytosis has been investigated. An in-vitro bioassay system was used in which mouse oocytes were exposed to calcium ionophore, A23187, in the presence and absence of leupeptin, before their fertilization and development to the blastocyst stage was assessed. We have demonstrated that the presence of leupeptin in the incubation medium, at concentrations of 1 micrograms/ml and 10 micrograms/ml during the first 10 min of cortical granule exocytosis, reversed the ionophore-induced decrease in the capacity of oocytes to fertilize and develop to blastocysts. The induction of exocytosis of cortical granules by calcium ionophore was confirmed using fluorescence microscopy. Using this technique, we also confirmed that leupeptin did not inhibit ionophore-induced cortical granule exocytosis, thus supporting the contention that leupeptin acted upon released cortical exudate. It was concluded that leupeptin acted by inhibiting proteases released into the perivitelline space during the early stages of cortical granule exocytosis. Based on these results it was proposed that leupeptin could be used to prevent premature loss of fertility of human oocytes which are inadvertently activated under in-vitro conditions. PMID- 1430118 TI - Effect of the number of inseminated spermatozoa on subsequent human and mouse embryonic development in vitro. AB - It has been shown, in both human and mouse in-vitro fertilization (IVF), that an excess number of spermatozoa in the insemination medium leads to reduced fertilization rates. In this study, we evaluated human embryonic development after dividing the oocytes of each of 62 IVF attempts into two groups on the basis of insemination with two widely used concentrations (50,000 and 100,000 spermatozoa/ml). The embryonic growth was retarded in the group inseminated with 100,000 spermatozoa/ml: significantly fewer fast developing embryos (4-cell and 5 to 8-cell stages) were found (53.4% in the 100,000/ml group and 65.5% in the 50,000 group; P less than 0.05). In two experimental series, mouse embryonic development was evaluated in the presence of 0, 50,000, 100,000 and 500,000 spermatozoa per ml. In the first series, the spermatozoa were present during 5-20 h after insemination, while in the second series, the spermatozoa were present during the whole culture period of 120 h. The development of mouse embryos was impaired when 500,000/ml spermatozoa were present during the whole culture period. In contrast with human IVF results, the presence of up to 500,000 spermatozoa during the first 20 h after insemination did not have any significant detrimental effect on blastocyst formation in the mouse. PMID- 1430119 TI - Gene activity and cleavage arrest in human pre-embryos. AB - There is a high rate of spontaneous cleavage arrest around the four- to eight cell stage of human development in vitro. Since this coincides with the time of activation of the embryonic genome it has been suggested that cleavage arrest may occur as a consequence of failure of gene activation. Gene expression in human pre-embryos is associated with an alpha-amanitin sensitive, qualitative change in protein synthesis. In order to ascertain the role of gene expression in cleavage arrest, we have examined the protein synthetic patterns of human pre-embryos which have undergone spontaneous cleavage arrest in vitro. Of 54 cleavage arrested embryos, 27 demonstrated evidence of synthesis of proteins sensitive to alpha-amanitin, suggesting that cleavage arrest is not always accompanied by failure of activation of the genome. Our results would also suggest that activation of gene expression is simply related to neither cell number nor time spent in culture since fertilization, but may be related to continuing karyokinesis. PMID- 1430120 TI - Factors controlling spontaneous human chorionic gonadotrophin in superfused first trimester placental explants. AB - We have recently reported that secretion of human chorionic gonadotrophin (HCG) by placental explants in superfusion is pulsatile. In this study, the factors involved in regulation of spontaneous pulsatility were examined. In superfusion, observed secretion of HCG by isolated cells was continuous, without spontaneous episodic hormonal secretion. However, this was not due to diminished viability of the cells since these cells continued to secrete sex steroids. In addition, the stimulatory response of HCG to a highly effective dose of 10(-9) M gonadotrophin releasing hormone (GnRH) analogue was also maintained. Preincubation of explants with low concentrations of cycloheximide (10(-6)M) markedly reduced baseline HCG levels as well as pulse amplitude, suggesting that episodic hormone secretion is in part dependent on protein synthesis. Moreover, preincubation of explants with labelled leucine has shown that the secretion of placental proteins is also episodic in superfusion. The pattern was similar but not identical to that of HCG. Addition of 1 min pulses of CaCl2 caused a significant release of HCG by superfused explants, suggesting that HCG secretion occurs through the release of storage granules. It was concluded that for the expression of spontaneous pulsatile secretion of HCG cell to cell contact/communication is necessary. HCG secretion is likely to reflect exocytosis of storage granules. HCG pulsatility is partly dependent on protein synthesis and this intermittent type of secretion can be documented by overall protein secretion by the superfused explant. PMID- 1430121 TI - 'Chemical curettage' using intrauterine methotrexate injection. AB - A 22-year-old woman with multiple urogenital anomalies presented for the second time with a blighted ovum situated in the rudimentary right horn of a uterus communicans bicornis. A dilatation and curettage was not possible owing to the inaccessibility of this horn. The first blighted ovum was aborted in 1989 (at age 21 years) following the use of intramuscular prostaglandin therapy. On this occasion, therapy was by the transvaginal, intrauterine (intra-amniotic) instillation of 100 mg methotrexate and a complete abortion of the products of conception occurred. Similar to the treatment of ectopic pregnancy, in certain cases, termination of intrauterine pregnancies using local methotrexate injection may be considered. PMID- 1430122 TI - When genes determine motherhood: problems in gestational surrogacy. AB - Gestational surrogacy in which a commissioning couple's egg and spermatozoon are united in vitro and the resulting embryo is implanted in a woman's uterus is, of all the new methods for overcoming infertility, the most genetically appealing. This is because the genes are often perceived as determining all aspects of human health, disease and even behaviour. Having a child with the genes of both parents has become far more attractive to most infertile couples than having one who is only genetically related to the father. However, gestational surrogacy has created a situation where one child has two mothers, each one claiming to be the 'true' mother having exclusive parental rights. Surrogacy arrangements also raise the question of the meaning of motherhood. PMID- 1430123 TI - The fraud conviction of Cecil B. Jacobson. PMID- 1430124 TI - Annual and sub-annual rhythms in human conception rates: time-series analyses show annual and weekday but no monthly rhythms in daily counts for last normal menses. AB - Methods of time-series analysis, which are widely used to good effect in physical sciences and econometrics, have found little use in much-needed analyses of cyclical biological phenomena. Here we apply those methods to analyses of rhythmic patterns in human conception rates. Our results confirm the annual periodicity of monthly counts of total viable conceptions, demonstrate a weekday rhythm reflecting interaction of conjugal coital rhythms with individual menstrual fertility cycles, and find no evidence of any other significant repeating pattern. PMID- 1430125 TI - The endometrial capillaries during the normal menstrual cycle: a morphometric study. AB - The areas of the capillary lumen, the entire capillary, the endothelial cells and the adventitia, as well as the thickness of the endothelial cell layer and the adventitia were studied using morphometric methods in endometrial samples from 34 fertile women who had a hormonal profile compatible with normal ovarian function. The biopsies were grouped around the luteinizing hormone surge. The results were calculated as mean values of 72-h periods and related to the mean levels of oestradiol and progesterone circulating in plasma 72 h prior to the biopsy. The results indicated that the sub-epithelial capillary plexus of the human endometrium undergoes dynamic changes during the normal menstrual cycle with a significant dilatation of the vessels during the post-ovulatory phase. A significant correlation was found between the area of the capillary lumen and the mean level of progesterone circulating in the plasma 72 h prior to the biopsy (P = 0.037). We conclude that the ovarian steroids produced during the normal menstrual cycle are likely to influence sub-epithelial vascularization causing dilatation in the post-ovulatory phase. This dilatation of the sub-epithelial capillaries may be related to the development of oedema appearing in the stroma at the time of the expected implantation. The possible functional significance of the capillary dilatation in terms of implantation, however, needs to be further investigated. PMID- 1430127 TI - Biochemical analysis of cervical mucus by nuclear magnetic resonance spectroscopy. AB - Biochemical evaluation of cervical mucus is difficult due to the characteristic rheological properties of this hydrogel. The application of high resolution nuclear magnetic resonance spectroscopy proved to be a valuable new method for differentiated biochemical analyses of human cervical mucus. A particular advantage is that it is non-destructive, that it can be applied to specimens of small volume and that no sample preparation, such as solubilization, is necessary. PMID- 1430126 TI - The aetiology of galactorrhoea in women with regular menstruation and normal prolactin levels. AB - Fourteen primary infertile women with expressible galactorrhoea associated with regular ovulatory cycles and normal basal prolactin levels (group A) were matched for age and weight with 14 infertile women with regular menstruation but no galactorrhoea (group B). Both groups showed equivalent increases in prolactin levels after stimulation with 200 micrograms thyrotrophin-releasing hormone (TRH) during the follicular and luteal phases of the menstrual cycle. Patients in group A had a greater increase in luteinizing hormone levels after 100 micrograms i.v. injection of a luteinizing hormone-releasing hormone during the follicular phase (P less than 0.05). Following a 60 mg oral dose of buspirone hydrochloride on day 22 of the menstrual cycle, patients in group A had a greater increase in prolactin levels than patients in group B (P less than 0.01). This reflects hyper responsive 5-hydroxytryptamine type 1A (5HT1A) receptors in group A patients and may explain the presence of galactorrhoea in these patients despite normal basal and post-TRH prolactin levels. PMID- 1430128 TI - Androstenedione as a predictor of ovarian hyperstimulation syndrome. AB - Serum concentrations of testosterone, 4-androstene-3,17-dione (androstenedione), dehydroepiandrosterone (DHA) and its sulphate and sex hormone-binding globulin (SHBG) were measured in 30 ovulatory women before and after down-regulation with gonadotrophin releasing-hormone analogue, prior to ovarian stimulation in a programme of in-vitro fertilization and embryo transfer. Nine of the women developed ovarian hyperstimulation syndrome (OHSS) while the others did not. Pretreatment values of androstenedione and the androstenedione:DHA ratios were higher and the testosterone:androstenedione ratios lower in the OHSS women. The decrease in androstenedione levels during down-regulation was greater and the absolute levels following down-regulation were lower in the OHSS group. Higher levels of SHBG and lower testosterone:SHBG ratios, an index of biologically active testosterone, were observed in the OHSS group. The isolated elevation in pretreatment androstenedione levels and the high SHBG levels make the OHSS group different from patients with polycystic ovarian disease. Pretreatment values of testosterone:androstenedione or testosterone/SHBG:androstenedione ratios and/or the decrease in androstenedione during down-regulation may be used as markers, prior to stimulation, for identifying women at risk of developing OHSS. PMID- 1430129 TI - Impaired glucose effectiveness in patients with polycystic ovary syndrome. AB - Insulin resistance and glucose intolerance are common features of polycystic ovary syndrome (PCOS). We have investigated the effect of glucose on the fractional glucose disappearance in patients with PCOS and in age- and weight matched control subjects. The minimal model method as applied to a frequently sampled intravenous glucose tolerance test was employed. The insulin sensitivity index (Si) and glucose effectiveness (SG) were calculated with the MINMOD program. Testosterone, androstenedione and free testosterone concentrations were significantly higher in PCOS subjects. Glucose-induced glucose clearance (SG) and insulin sensitivity were significantly lower in PCOS subjects than controls [SG: 2.7 +/- 0.3 versus 1.8 +/- 0.1 x 100/min; P less than 0.01; Si: 133.4 +/- 20.0 versus 65.6 +/- 6.4/min (nmol/ml)]. Six PCOS women had an SG value within the normal range (greater than 2.0 x 100/min) but had a similar Si to that found in PCOS women with abnormal SG. We suggest that independent alterations in both glucose- and insulin-mediated glucose uptake occur in patients with PCOS. The underlying disturbance in glucose effectiveness may be similar to that found in familial non-insulin dependent diabetes mellitus. PMID- 1430130 TI - The correlation between interleukin 2 and soluble interleukin 2 receptors to oestradiol, progesterone and testosterone levels in periovulatory follicles of in vitro fertilization patients. AB - The present study was performed to evaluate the correlation between follicular fluid levels of interleukin 2 (IL-2) and IL-2 soluble receptor (sIL-2R), oestradiol, progesterone and testosterone levels, oocyte fertilization, embryo quality and pregnancy rates. Twenty-eight patients with a pure tubal factor and undergoing in-vitro fertilization and embryo transfer were randomly chosen and treated with gonadotrophin releasing hormone agonist (GnRHa) in the midluteal phase (long protocol) coupled with follicular phase administration of human menopausal gonadotrophin. Transvaginal follicular aspiration was performed 36 h after human chorionic gonadotrophin administration, followed 48 h later by embryo transfer. One hundred and twenty-three follicular fluids were sampled. The mean follicular fluid levels (+/- SD) were 2.30 +/- 0.80 fmol for IL-2, 458.2 +/- 236.0 units/ml for sIL-2R, 28.5 +/- 58.1 ng/ml for oestradiol, 2360.5 +/- 2846 ng/ml for progesterone and 7.22 +/- 7.08 ng/ml for testosterone. There was a significant (P less than 0.01) correlation between IL-2 and testosterone levels. No correlation was found between the lymphokines and serum oestradiol, follicular fluid progesterone, oocyte fertilization, embryo quality and pregnancy. It may be concluded that significant concentrations of IL-2 and sIL-2R exist in follicular fluid. Wide variations in follicular IL-2 and sIL-2R concentrations of different follicles were found in the same patients. PMID- 1430131 TI - Spontaneous luteinizing hormone surges can be reliably prevented by the timely administration of a gonadotrophin releasing hormone antagonist (Nal-Glu) during the late follicular phase. AB - A new gonadotrophin releasing hormone antagonist (Nal-Glu) was used during the late follicular phase of the natural cycle in order to prevent spontaneous surges of luteinizing hormone (LH). Eight regularly ovulating women (group 1) received two injections of Nal-Glu (5 mg) administered 48 h apart when plasma oestradiol levels exceeded 125 pg/ml. Human menopausal gonadotrophin (HMG, 225 IU) was administered simultaneously with Nal-Glu and repeated every 12 h thereafter until either a spontaneous LH surge occurred or human chorionic gonadotrophin (HCG, 5000 IU) was administered. HCG was arbitrarily administered 48 h after the second Nal-Glu injection. Six other women (group 2) receiving only HMG served as controls. In seven of the eight women in group 1, LH and progesterone remained low for 96 h following Nal-Glu, i.e. until HCG administration. In the remaining woman in this group, LH started to rise 12 h before HCG injection. In this group, Nal-Glu did not interfere with follicular development or the plasma profile of oestradiol. All women developed one single dominant follicle with the exception of one subject who had already spontaneously developed two dominant follicles prior to administration of Nal-Glu and HMG. In group 2, LH rose spontaneously in all women before the planned HCG injection. The luteal phase was apparently not altered by Nal-Glu. These results suggest that Nal-Glu administration during the late follicular phase of natural cycles supported by HMG, can prevent the spontaneous LH surge while not interfering with follicular growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430132 TI - Early changes of affinity and binding sites of progesterone and oestrogen receptors in decidua exposed to RU 486. AB - Sixty patients with 6-7 weeks of amenorrhoea were randomly allocated to three groups. The women in the first group (control) took a placebo 24 h before undergoing a vacuum aspiration. The patients in the second and third groups were given 200 mg of RU 486 orally, 12 or 24 h before surgical interruption of their pregnancy. Decidua were collected and frozen in liquid nitrogen. By Scatchard plot analysis, the number of cytosolic binding sites (1798 +/- 803 fmol/mg DNA) of progesterone in decidua in the control group was significantly reduced (P less than 0.01) to 696 +/- 408 or 626 +/- 179 fmol/mg DNA by RU 486 treatment for 12 or 24 h respectively. The dissociation constants of both cytosolic and nuclear progesterone receptors in RU 486-exposed decidua were increased (P less than 0.01). The number of nuclear binding sites of oestrogen receptor was significantly higher (P less than 0.05) in decidua with RU 486 treatment for 12 h (178 +/- 77 fmol/mg DNA) compared to the control (89 +/- 32 fmol/mg DNA). The results suggest that RU 486 might regulate progesterone and oestrogen receptors in the decidua of early human pregnancy, either directly or indirectly. PMID- 1430133 TI - Consecutive versus alternating cycles of ovarian stimulation using human menopausal gonadotrophin. AB - Ovarian stimulation is an effective treatment for patients with ovulatory dysfunction and unexplained infertility. An initial report has suggested that consecutive cycles of ovarian stimulation can be employed without causing a diminished response in the second cycle. However, this observation has neither been confirmed nor has a regimen of consecutive stimulation cycles been compared to one of alternating stimulation cycles. Accordingly, 44 consecutive and 54 alternating cycles of stimulation were evaluated in patients (n = 42) who were treated with human menopausal gonadotrophin (HMG) alone. Human chorionic gonadotrophin (HCG) 10,000 IU was administered i.m. when at least one follicle exceeded 16 mm in mean diameter, and this was followed by either intercourse or intrauterine insemination. Using each patient as her own control, we were unable to demonstrate any differences in mean HMG dose requirements, endocrine parameters or follicular development on the day of HCG administration, or ovulation rates in the second consecutive cycle compared to the second alternating cycle. Clinical pregnancies resulted significantly more often in a consecutive cycle (8/22) than in an alternating cycle (2/27, P = 0.029). We conclude that consecutive cycles of ovarian stimulation with HMG are not detrimental and may, in fact, result in increased cycle fecundity compared to alternating stimulation cycles. PMID- 1430134 TI - The 24 h pattern of pulsatile luteinizing hormone, follicle stimulating hormone and prolactin release during the first 8 weeks of lactational amenorrhoea in breastfeeding women. AB - In women, breastfeeding results in a variable period of ovarian inactivity which is apparently related to suppression of the normal pulsatile release of luteinizing hormone (LH). However, pulse profiles had only been studied during the daytime. Since resumption of pulsatile LH secretion during puberty is initiated at night, the present study determined the pattern of pulsatile LH secretion in relation to that of follicle stimulating hormone (FSH) and prolactin, and suckling and ovarian activity at 4 and 8 weeks postpartum in 20 fully breastfeeding women with lactational amenorrhoea. Blood samples were withdrawn at 10 min intervals for 24 h from 0900 h to 0900 h at either 4 weeks (n = 9) or 8 weeks (n = 11) postpartum, while the mothers and babies continued their normal pattern of suckling activity. At 4 weeks postpartum, no LH pulses occurred over 24 h in six of the nine women while one (n = 1) or two (n = 2) LH pulses occurred in three of the nine women. In contrast, LH pulses were present in nine of the 11 women at 8 weeks postpartum. The pulse frequency varied considerably from two to eight pulses over the 24 h and there was no influence of the time of day or sleep on the time of the pulse release. Lactational amenorrhoea was maintained for at least 10 weeks afterwards and there was no relationship between the time of resumption of ovarian activity and the presence or absence of pulsatile LH secretion at 4 or 8 weeks postpartum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430135 TI - Density differences between spermatozoa with antisperm autoantibodies and spermatozoa covered with antisperm antibodies from serum. AB - Autoantibody-carrying spermatozoa from infertile men were processed using a discontinuous Percoll gradient. The treatment yielded a sperm fraction with significantly reduced antibody loading on the sperm head but did not affect antibody binding to the sperm tail. The immunodepleted sperm preparation demonstrated fertilizing ability when used in in-vitro fertilization. Normal, antibody-free semen samples were coated in vitro with antisperm antibodies from serum, followed by Percoll gradient centrifugation. No significant separation of antibody-free spermatozoa was obtained, regardless of the antibody binding site. PMID- 1430136 TI - Outcome of treatment subsequent to the elective cryopreservation of all embryos from women at risk of the ovarian hyperstimulation syndrome. AB - From 1st June 1989 to 31st May 1991, 78 women with a serum oestradiol level greater than 3500 pg/ml on the day of the ovulatory trigger, following pituitary suppression with buserelin and ovarian stimulation with human menopausal gonadotrophins (HMG), had all their embryos electively cryopreserved at the pronucleate stage to minimize the risk of developing ovarian hyperstimulation syndrome (OHS). Treatment with buserelin was continued in the luteal phase. A median of 19 oocytes (range 7-43) was obtained and 12 embryos (range 1-37) frozen per cycle. Twenty-one (27%) women developed OHS (six severe). Women developing OHS had higher (P less than 0.05) serum oestradiol concentrations on the 7th day after oocyte retrieval, compared to those who did not. No differences were found for any of the following criteria: aetiology of infertility, age, total dose of HMG, number of oocytes, fertilization rate or freeze-thaw survival of embryos. Subsequently, 125 frozen-thawed embryo replacements have been undertaken, using buserelin and hormone replacement therapy (HRT) (n = 93) or natural cycles (n = 32). The overall freeze-thaw survival and implantation rates per embryo were 71.8 and 11.7%, respectively. The pregnancy rates in natural cycles (19%) and buserelin/HRT cycles (29%) were not significantly different. PMID- 1430137 TI - Ovarian torsion: a complication of GIFT. A report on two cases and literature review. AB - Two cases of ovarian torsion after gamete intra-Fallopian transfer are described and the roles of ovarian manipulation during the procedure, ovarian hyperstimulation and pregnancy as predisposing factors are discussed. The relevant literature is reviewed. PMID- 1430138 TI - Results of routine syphilitic and human immunodeficiency virus (HIV) serology in infertility. AB - While it has been accepted practice to screen women undergoing infertility evaluation for syphilis, there are few data in the literature regarding the seroprevalence of human immunodeficiency virus (HIV) infection in infertile patients despite the increasing number of HIV-positive women. In the present study, six out of 2137 infertility patients were seropositive for syphilis (0.28%) and four out of 791 were HIV positive (0.5%). All four women with HIV antibodies had negative tests for syphilis and none of them related any risk factor for HIV infection on their initial visit. The 0.5% sero-positivity rate found in our study warrants routine HIV testing in infertile patients. PMID- 1430139 TI - The usefulness of endometrial biopsy for luteal phase evaluation in infertility. AB - To assess the usefulness of the late luteal phase endometrial biopsy in infertility, we evaluated a total of 1492 biopsies performed in 1055 patients. Of these women, 699 underwent one biopsy during spontaneous ovulatory cycles, 288 had two, 57 had three, nine had four, and five biopsies were done in two patients. As controls we included 45 fertile women who were requesting contraception. We analysed histological dating of the endometrium and its abnormality rates in first and successive biopsy specimens, as well as the association of the pregnancy outcome with the endometrial patterns and treatment for luteal phase deficiency (LPD). Our results show firstly that diagnosis of LPD in both infertile and fertile women represents only a chance event; secondly, histological endometrial adequacy or inadequacy in the cycle of conception or in previous cycles is not related to the outcome of pregnancy in infertile patients. Finally, treatment of LPD does not improve pregnancy outcome in infertile women. Thus, luteal phase evaluation by histological dating of the endometrium is not worthwhile. PMID- 1430140 TI - An evaluation of couples with failure of fertilization in vitro. AB - Attempts at in-vitro fertilization (IVF) may be used as a method of evaluating whether in a given couple, the inability of the sperm to fertilize the oocyte may be the cause of infertility. We evaluated all IVF patients in our practice who had at least one cycle with no fertilization to determine how often this was an isolated event or was repeated in multiple cycles; would poor semen quality be found as a frequent cause; and how well can a donor sperm or oocyte 'probe' uncover which of the two is the problem? Of 35 couples who used their own gametes exclusively, 30 (85.7%) had at least one cycle with zero fertilization; 42.5% of those failing to fertilize in cycle 1 and 35% of those failing in cycle 2 had a subnormal concentration of motile spermatozoa, morphology or hypo-osmotic swelling test scores. The pregnancy rate per cycle with both husband's and wife's gametes was only 2.3% (3/130), but was 8.3% for those using donor spermatozoa (3/36) and 18.2% (2/11) for donor oocytes. Thus, failing to fertilize in a given cycle does not necessarily predict failure to fertilize in a subsequent cycle, but does predict a poor fertility outcome unless donor gametes are used. PMID- 1430141 TI - Costs in relation to effects of in-vitro fertilization. AB - A comparison has been made between in-vitro fertilization (IVF) and its most important alternative, tubal surgery. Medical results and financial costs have been taken into consideration. It is concluded that IVF must be regarded as a regular fertility treatment. The cost-effectiveness of IVF, in terms of the average treatment costs per full-term pregnancy, is approximately NLG 25,000, which is in line with that of tubal surgery. The deviation around the average is large, both for IVF and for tubal surgery. PMID- 1430142 TI - Effects of indoleamines on sperm motility in vitro. AB - Indoleamines are products of the pineal gland and are postulated to play an antigonadotrophic role in the reproductive system of mammals. In humans, indoleamines have been localized in tissue fluids such as plasma, serum and cerebrospinal fluid. Because indoleamines exhibit antigonadotrophic properties, the authors examined whether these agents cause inhibitory effects on sperm motility. In this study, time and dose-dependent inhibition of sperm motility by indoleamines was observed. Furthermore, the presence of indoles in incubation medium decreased sperm velocity. These data suggest that the presence of high doses of indoles in reproductive fluids may inhibit sperm motility and velocity. PMID- 1430143 TI - Spontaneous and ionophore induced acrosome reaction in asthenozoospermic infertile semen. AB - Spontaneous and ionophore-induced ability of spermatozoa to acrosome-react was examined in asthenozoospermic infertile patients and fertile donors. Spermatozoa were washed free of seminal plasma and capacitated in B2 medium for 2 h at 37 degrees C. Subsequently 5, 10, 20 and 30 microM A23187 (final concentrations) were added to equal aliquots of these samples and incubated for an additional 30 min. The acrosome reaction was then determined by the triple stain technique. The percentage of spontaneous reaction (no ionophore) in asthenozoospermic samples was similar to that in fertile samples (4.2 and 3.8, respectively). However, the ionophore-induced reaction rate remained significantly lower in asthenozoospermic samples than in normozoospermic samples. PMID- 1430144 TI - Pronuclear, cleavage and blastocyst histories in the attempted preimplantation diagnosis of the human hydatidiform mole. AB - We report a study of fertilization, syngamy and embryonic development in 14 oocytes from a woman with four previous pregnancies involving complete hydatidiform moles. Serial observations of pronuclear movements and syngamy were compared to those in a group of 10 multipronucleate embryos from other patients. One embryo and possibly two others developed normally or near-normally. The others displayed immediate cleavage or had one or three pronuclei. The tripronucleate eggs displayed various anomalous forms of growth. The unipronucleate eggs passed through a double form of syngamy, which might have involved chromosome doubling, and could have developed as androgenetic diploids. We suggest a hypothesis to explain these unusual observations. PMID- 1430145 TI - Is the human oocyte plasma membrane polarized? AB - Using scanning electron microscopy, we have shown that the plasma membrane of the human metaphase II oocyte is organized in evenly spaced, short microvilli of 1-3 microns in length. In contrast to other mammals studied to date, there is no microvillus-free area overlying the metaphase spindle and there were no other indications of polarization at this level of organization. Functional polarity of the plasma membrane, studied using localized microsurgery of the zona pellucida followed by insemination, suggests that sperm fusion and entry in the human may occur anywhere over the oocyte surface. Aged oocytes and those exposed to acidic Tyrode's solution had surfaces which were not homogeneously covered by microvilli. Oocytes exposed to a sucrose solution and subzonally injected with spermatozoa showed evidence of partial cortical granule exocytosis. PMID- 1430146 TI - Abstracts of the 8th annual meeting of the European Society of Human Reproduction and Embryology. The Hague, The Netherlands, 5-8 July 1992. PMID- 1430147 TI - Morphology of demyelination in the human central nervous system. AB - The principles of the neuropathological classification of disorders of central nervous system myelin are recalled. They are illustrated by a few selected examples. Dysmyelination is characterized by the production of an abnormal and unstable myelin sheath; it is often associated with hypomyelination (paucity of myelin formation) and is due to metabolic disorders. It is the main process in leukodystrophies. Storage of different lipids (e.g. sulfatides, long-chain fatty acids) or associated pathology of various cell types (in Alexander's disease, for example) are used for classifying these disorders. Biochemical and genetic characterizations are presently ongoing. Demyelination is the destruction of apparently normal myelin. It is often followed by remyelination. Our present knowledge on the neuropathology of multiple sclerosis, the most common demyelinating disease, is summarized. Cell-mediated demyelination affects the myelin sheaths for an obscure reason. The causes of the multifocal and sharply demarcated plaques, and of the fading of the remyelination process at the edge of some plaques, are not clear. A few examples of demyelinating diseases of known etiology and of various mechanisms are given. The similarities between acute disseminated leukoencephalitis and experimental autoimmune encephalitis are stressed. In progressive multifocal leukoencephalopathy, chronic infection of oligodendrocytes by JC virus induces poorly defined areas of demyelination. In AIDS, the pathogenesis of the myelin change is unclear. Macrophages may be responsible. Toxic and vascular disorders provide also good models for the understanding of mechanisms of demyelination. PMID- 1430148 TI - Macrophage responses and myelin clearance during Wallerian degeneration: relevance to immune-mediated demyelination. AB - Macrophages are important effector cells in immune-mediated demyelination. Current concepts regarding their entry and activation focus on the effects of T cell-derived cytokines. This presentation describes the responses of macrophages and microglia to a non-inflammatory, non-immune injury, Wallerian degeneration. During Wallerian degeneration in the peripheral nervous system (PNS), macrophages are promptly and abundantly recruited from the circulation, and myelin clearance is prompt. In the central nervous system (CNS), the appearance of macrophages is markedly slower, and entry from the circulation is modest or absent. Myelin clearance is similarly delayed. The nature of the factors promoting macrophage entry and activation in Wallerian degeneration, and the bases for the differences between PNS and CNS, are relevant to current issues in immune-mediated demyelination. PMID- 1430149 TI - Stromal macrophages of the choroid plexus situated at an interface between the brain and peripheral immune system constitutively express major histocompatibility class II antigens. AB - Using immunocytochemistry we have shown that there is a population of macrophages within the stroma of the choroid plexus of rats and mice which expresses high levels of major histocompatibility complex Class II antigens. In whole mount preparations of the choroid plexus, the morphology and regular distribution of these cells is similar to the Langerhans cells of the skin. These cells reside at an important interface between the central nervous system and the peripheral immune system and their possible role in immune-mediated diseases of the central nervous system is discussed. PMID- 1430150 TI - The role of macrophages in demyelination. AB - Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS). In particular in the CsA-induced chronic relapsing form (CREAE), pronounced demyelination occurs, in temporal association with relapses. It is still a matter of discussion which cell type ultimately is responsible for the actual process of demyelination. Macrophages, cytotoxic T lymphocytes and also astrocytes are possible candidates. In this short overview, the role of macrophages in the pathogenesis of EAE is discussed. It is shown that in particular, newly recruited macrophages play a crucial role in the generation of clinical signs. Possible mechanisms by which macrophages are involved in the pathogenesis of demyelinating diseases are presented. PMID- 1430151 TI - Production of macrophage colony-stimulating factor by astrocytes and brain macrophages. AB - Morphological hallmarks of inflammatory and degenerative diseases of the brain are hypertrophy of astrocytes and accumulation of macrophages recruited from circulating blood monocytes and/or from resident macrophages, the so-called microglial cells. Recently, production of granulocyte-macrophage colony stimulating factor (GM-CSF) by astrocytes has been suggested to contribute to the macrophage response. Here we report that in addition to GM-CSF, murine astrocytes also produce macrophage (M)-CSF upon stimulation with tumor necrosis factor alpha, interleukin-1 and lipopolysaccharides. The bioactivity detected in supernatant of astrocytes was characterized using the M-CSF-dependent cell line M NFS-60 and neutralizing anti-M-CSF antibodies. RNase protection analysis showed M CSF mRNA already in unstimulated astrocytes without striking up-regulation by the stimuli. Thus, in astrocytes the expression of the M-CSF gene is predominantly regulated at the posttranscriptional level. PMID- 1430152 TI - Cytokines in neuroinflammatory disease: role of myelin autoreactive T cell production of interferon-gamma. AB - Many cytokines must be considered as effector and immunoregulatory molecules in neuroinflammatory diseases such as multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). We have studied the potential role of interferon-gamma (IFN-gamma) in the pathogenesis of these diseases, since this cytokine has a number of important effects such as macrophage activation, induction of MHC class I and class I antigens, and T cell homing. An immunospot assay that allows enumeration of single cells secreting IFN-gamma after short term culture in vitro of mononuclear cell suspensions has been used. In EAE, increased numbers of IFN-gamma-secreting cells (IFN-gamma-sc) appear in the central nervous system shortly before onset of clinical signs. Such cells also increased during pharmacologically induced relapse of EAE. In later stages of EAE, memory T cells that produced IFN-gamma in response to presented antigen, recognized multiple regions of the myelin basic protein (MBP), showing that (i) myelin autoreactive T cells have the functional ability to produce this cytokine, (ii) the concept of immunodominance as to autoantigen peptide reactivity is non absolute and time-dependent. In multiple sclerosis (MS) there are increased numbers of IFN-gamma-sc among the CSF cells. Also, there are increased numbers of memory T cells, strongly enriched to the cerebrospinal fluid, which upon recognition of several myelin antigens and several MBP peptide stretches, produce IFN-gamma. Taken together, the data are consistent with a role for IFN-gamma as a key mediator in inflammatory demyelinating diseases. PMID- 1430153 TI - Multiple sclerosis and vitamin B12 metabolism. AB - Multiple sclerosis (MS) is occasionally associated with vitamin B12 deficiency. Recent studies have shown an increased risk of macrocytosis, low serum and/or CSF vitamin B12 levels, raised plasma homocysteine and raised unsaturated R-binder capacity in MS. The aetiology of the vitamin B12 deficiency in MS is often uncertain and a disorder of vitamin B12 binding or transport is suspected. The nature of the association of vitamin B12 deficiency and MS is unclear but is likely to be more than coincidental. There is a remarkable similarity in the epidemiology of MS and pernicious anaemia. Vitamin B12 deficiency should always be looked for in MS. The deficiency may aggravate MS or impair recovery. There is evidence that vitamin B12 is important for myelin synthesis and integrity but further basic studies are required. PMID- 1430154 TI - The differentiation of glial cell progenitor populations following transplantation into non-repairing central nervous system glial lesions in adult animals. AB - The non-repairing nature of the locally x-irradiated ethidium bromide (EB) induced demyelinating white matter lesion has been further validated by showing that injections of two cultures which promote host remyelination of EB lesions in normal tissue do not do so in x-irradiated lesions. The behaviour of an oncogene immortalized glial cell line and a growth-factor-expanded glial progenitor population have been examined following transplantation into the non-repairing EB lesion. Our studies indicate that the selected glial cell populations were each capable of establishing glial environments around demyelinated axons. Extensive oligodendrocyte remyelination with little astrocytic presence was observed in lesions transplanted with growth-factor-expanded optic nerve progenitors, while less extensive oligodendrocyte remyelination with the establishment of astrocyte like cells was found in lesions transplanted with ts A58-SV40T immortalized glial cells. Prolonged expansion of both populations resulted in a loss of differentiation to normal glial phenotypes. PMID- 1430155 TI - Central nervous system demyelination and remyelination in multiple sclerosis and viral models of disease. AB - The mechanisms of myelin injury and repair were studied in acute multiple sclerosis lesions and in a murine model of demyelination induced by a virus. Injury to oligodendrocytes resulting in degeneration of inner glial loops and inner myelin lamellae (dying-back oligodendrogliopathy) was observed by electron microscopy in brain biopsies of acute demyelinating lesions. Attempts at central nervous system remyelination as manifested by thinly myelinated axons and proliferation of oligodendrocytes were observed at the edge of many acute plaques. To develop therapeutic strategies to inhibit demyelination or promote remyelination, mice infected intracranially with Theiler's virus (a picornavirus) were studied. Experimental manipulation of Theiler's virus-infected mice by treatment during chronic demyelinating disease with immunoglobulins directed at normal spinal cord antigens or with monoclonal antibodies which deplete CD4 or CD8-positive T cells resulted in augmentation of new myelin synthesis. These observations suggest that disturbances in the myelinating function of oligodendrocytes, events not accompanied by death of these cells, may be among the earliest pathological events in multiple sclerosis. Experiments using the Theiler's virus model of demyelination indicate that manipulation of the immune response has the potential to promote central nervous system remyelination and functional recovery in multiple sclerosis. PMID- 1430156 TI - The effects of high-dose methylprednisolone on gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid measurements in multiple sclerosis. AB - Blood-brain barrier (BBB) disruption is probably the first event in the lesion development in multiple sclerosis (MS). This stage can be visualized by gadolinium-enhanced magnetic resonance (MR) imaging of the brain. Serial MR imaging studies have indicated a continuous spectrum of disease activity with waxing and waning of acute lesions, even in clinically stable MS patients. High dose intravenous methylprednisolone (MP) has a beneficial clinical effect; reduces gadolinium enhancement, indicating improvement of BBB integrity; and, in MS patients, decreases intrathecal immunoglobulin synthesis with reduction of cerebrospinal fluid (CSF) myelin basic protein (MBP). A correlative triad is noted between gadolinium enhancement, clinical improvement, and decrease of CSF MBP following MP treatment, indicating a relationship between restoration of BBB integrity, clinical improvement and decrease of myelin breakdown. It is not clear whether MP interferes primarily with the process of demyelination or reacts non specifically with its mediators. PMID- 1430158 TI - Macrophages and the glucocorticoids. AB - Macrophages fulfill such functions as (i) housekeeping and scavenging, (ii) protective and defense, and (iii) memory. Glucocorticoids are hormones also used as anti-inflammatory and immuno-suppressive drugs. They act on the many functions of macrophages, mainly by interfering with functions (ii) and (iii). Glucocorticoids interfere with these macrophage functions by modulating the production of inflammatory mediators such as cytokines, phospholipid-derived mediators, proteases, oxygen metabolites. For inducing these effects, glucocorticoids interact with their receptors, transcription factors that recognize specific genomic sequences, glucocorticoid responsive elements (GRE). Glucocorticoids modulate the transcription of genes in association with other transcription factors such as Fos, Jun, CREB, These combinatorial associations- differing according to the differentiation and/or activation state of the cell- may therefore produce a fine-tuning of the induction or repression of genes. These mechanisms shed new light for understanding the complexity of glucocorticoid effects on macrophage function in the inflammatory reaction. PMID- 1430157 TI - Glucocorticoid regulation of eicosanoid production by glial cells under basal and stimulated conditions. AB - We measured the production of two eicosanoids, prostaglandin E2 and thromboxane B2, by rat glial cell cultures under basal conditions, following stimulation with phorbol-12-myristate-13-acetate and the bacterial endotoxin lipopolysaccharide, and following treatment with synthetic glucocorticoids. Stimulation of rat glial cells in culture with either phorbol-12-myristate-13-acetate or lipopolysaccharide caused a 1.5-5.0-fold increase in prostaglandin E2 production, but did not affect thromboxane production. Pretreatment of the cultures with dexamethasone markedly inhibited the stimulated production of prostaglandin E2 but had only a modest effect on basal production. Dexamethasone did not affect the activity of the enzyme protein kinase C, a putative regulator of eicosanoid synthesis. Our findings show that glucocorticoids have the potential to modulate central nervous system eicosanoid production particularly under conditions of stimulated production, such as inflammatory and demyelinating disorders. This mechanism may explain, at least in part, the therapeutic benefit of glucocorticoids in patients with multiple sclerosis. PMID- 1430159 TI - Development and regeneration in the O-2A lineage: studies in vitro and in vivo. AB - This brief review discusses selected aspects of our studies on the control of division and differentiation of the glial precursor cells which give rise to oligodendrocytes. For more extensive reviews on this topic, the reader is referred to recent reviews by Raff (1989), Richardson et al. (1991), Noble (1991) and Noble et al. (1991). PMID- 1430160 TI - Air-rotor stripping and lower incisor extraction treatment. PMID- 1430161 TI - 1991 JCO orthodontic practice study. 3. Practice growth. PMID- 1430162 TI - Oral hygiene compliance: a clinical investigation. PMID- 1430163 TI - Efficient and effective infection control. PMID- 1430164 TI - Remodeling: exterior additions. PMID- 1430165 TI - Evaluation of maxillary disjunction with bone densitometry. PMID- 1430166 TI - Horizontal growth of the soft-tissue nose relative to maxillary growth. PMID- 1430167 TI - The asymmetrical "T" archwire. PMID- 1430168 TI - Clinical considerations in the use of protraction headgear. PMID- 1430169 TI - Orthodontic associateships: how to succeed. PMID- 1430170 TI - Do sealants seal? An SEM investigation. PMID- 1430171 TI - Forced eruption: an alternative to extraction or periodontal surgery. PMID- 1430172 TI - Orthodontic pliers. PMID- 1430173 TI - Swivel key for palatal expansion appliances. PMID- 1430174 TI - The tip-edge concept: eliminating unnecessary anchorage strain. PMID- 1430175 TI - A bonded space maintainer. PMID- 1430176 TI - Molar distalization with superelastic NiTi wire. PMID- 1430177 TI - Management skills linked to the profitability of large practices. PMID- 1430178 TI - How to keep cement from blocking a molar tube. PMID- 1430179 TI - Effective use of a treatment communications coordinator. PMID- 1430180 TI - Overjet reduction with a preadjusted appliance system. PMID- 1430181 TI - Pain in the early stages of orthodontic treatment. PMID- 1430182 TI - Molar uprighting with crossed tipback springs. PMID- 1430183 TI - Cephalometric evaluation of skeletal open- and deep-bite tendencies. PMID- 1430184 TI - A new approach to staying on time. PMID- 1430185 TI - Designing adult areas. PMID- 1430187 TI - Use of stamped chart notations to enhance patient compliance. PMID- 1430186 TI - Class II bimaxillary protrusion treated with magnetic forces. PMID- 1430188 TI - Occlusograms in orthodontic treatment planning. PMID- 1430189 TI - Modified Nance appliance for unilateral molar distalization. PMID- 1430190 TI - Patient motivation and education products. PMID- 1430191 TI - Indirect fabrication of a bonded lower lingual retainer. PMID- 1430192 TI - Class II treatment with elastodontics. PMID- 1430193 TI - Frictional properties of metal and ceramic brackets. PMID- 1430194 TI - Cancer risks from germline p53 mutations. PMID- 1430195 TI - Modulation of transforming growth factor-beta 1 antiproliferative effects on endothelial cells by cysteine, cystine, and N-acetylcysteine. AB - Early passaged bovine pulmonary artery endothelial cells exposed to 0.1-2.0 ng/ml transforming growth factor-beta 1 (TGF-beta 1) showed concentration-dependent growth inhibition, as assessed by [3H]thymidine labeling and cell counts, over a 96-h interval. Most of the inhibition of [3H]thymidine labeling measured at 96 h persisted when the medium was replaced with TGF-beta 1-free medium after 24 h, but the inhibition of labeling was prevented by the presence of anti-TGF-beta 1 antibody in the replacement medium. Additions of 2 mM cysteine, 1 mM cystine, or 2 mM N-acetylcysteine at the time of the initial addition of TGF-beta 1 blocked the inhibitory effect of TGF-beta 1 on [3H]-thymidine labeling when this was assessed after 72-96 h, but not at earlier times. Prevention of the inhibitory effect on cellular proliferation produced by cysteine, cystine and N acetylcysteine was associated with elevation of cellular glutathione that was present at 48-96 h. There was no evidence for direct inactivation of TGF-beta 1 by the thiol-amino acids. Conditioned medium from TGF-beta 1-treated endothelial cells inhibited proliferation of mink lung carcinoma (CCL64) cells, supporting a previously reported concept of autocrine production of TGF-beta 1 by the endothelial cells. The inhibitory action of the conditioned medium was partially prevented when 1 mM cysteine was added during conditioning. Thus, TGF-beta 1 treatment of endothelial cells appears to set off autocrine production by these cells of TGF-beta 1 that perpetuates the inhibition of cellular proliferation. Replenishment of cellular glutathione with thiol-amino acids counteracts the growth-inhibitory effect of TGF-beta 1 through a currently undefined mechanism. PMID- 1430196 TI - Paradoxical withdrawal of reflex vasoconstriction as a cause of hemodialysis induced hypotension. AB - Acute hypotension is an important complication of hemodialysis, but the underlying mechanisms remain poorly understood. Because hemorrhage-induced hypovolemia can trigger a sudden decrease in sympathetic activity resulting in bradycardia and vasodilation, we hypothesized that hemodialysis-induced hypovolemia also can trigger the same type of vasodepressor reaction, which would exacerbate the volume-dependent fall in blood pressure. We therefore measured blood pressure, vascular resistance, and sympathetic nerve activity (intraneural microelectrodes) during sessions of maintenance hemodialysis in 7 patients with and 16 patients without a history of hemodialysis-induced hypotension. During hemodialysis, blood pressure at first remained unchanged as calf resistance increased in both hypotension-resistant (from 37 +/- 4 to 49 +/- 5 U, P < 0.05) and hypotension-prone (from 42 +/- 6 to 66 +/- 12 U, P < 0.05) patients; sympathetic activity increased comparably in the subset of patients in whom it could be measured. With continued hemodialysis, calf resistance and sympathetic activity increased further in the hypotension-resistant patients, but in the hypotension-prone patients the precipitous decrease in blood pressure was accompanied by decreases in sympathetic activity, vascular resistance, and heart rate as well as symptoms of vasodepressor syncope. On an interdialysis day, both groups of patients increased vascular resistance normally during unloading of cardiopulmonary baroreceptors with lower body negative pressure and increased heart rate normally during unloading of arterial baroreceptors with infusion of nitroprusside. These findings indicate that in a group of hemodialysis patients without diabetes or other conditions known to impair autonomic reflexes, hemodialysis-induced hypotension is not caused by chronic uremic impairment in arterial or cardiopulmonary baroreflexes but rather by acute, paradoxical withdrawal of sympathetic vasoconstrictor drive producing vasodepressor syncope. PMID- 1430197 TI - Sporadic hypertrophic cardiomyopathy due to de novo myosin mutations. AB - Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. While missense mutations in the beta cardiac myosin heavy chain (MHC) gene account for approximately half of all cases of familial hypertrophic cardiomyopathy, the molecular causes of sporadic hypertrophic cardiomyopathy are unknown. To determine whether beta cardiac MHC mutations are also associated with sporadic disease, we screened this gene in seven individuals with sporadic hypertrophic cardiomyopathy. Mutations in the beta cardiac MHC genes were identified in two probands with sporadic disease. In that their parents were neither clinically nor genetically affected, we conclude that mutations in each proband arose de novo. Transmission of the mutation and disease to an offspring occurred in one pedigree, predicting that these are germline mutations. The demonstration of hypertrophic cardiomyopathy arising within a pedigree coincident with the appearance of a de novo mutation provides compelling genetic evidence that beta cardiac MHC mutations cause this disease. We suggest that de novo mutations account for some instances of sporadic hypertrophic cardiomyopathy and that these mutations can be transmitted to children. The clinical benefits of defining mutations responsible for familial hypertrophic cardiomyopathy should also be available to some patients with sporadic disease. PMID- 1430198 TI - Regulation of lipoprotein lipase in the diabetic rat. AB - Diabetes mellitus is associated with a reduction of lipoprotein lipase (LPL) activity and development of hypertriglyceridemia. In the current experiments the mechanisms involved in the regulation of LPL have been examined in control rats, streptozocin-induced diabetic rats, and diabetic rats treated chronically or with a single injection of insulin. Diabetes decreased adipose tissue LPL activity partially by decreasing immunoreactive LPL protein and the steady-state levels of LPL mRNA, but primarily by reducing the catalytic activity of LPL. Both chronic and acute insulin increased adipose tissue LPL activity by correcting the defect in the catalytic activity of LPL and increasing immunoreactive LPL protein; however, only chronic insulin restored LPL mRNA levels to normal. In the heart, LPL activity tended to be elevated with diabetes in parallel to an increase in immunoreactive LPL protein even though levels of LPL mRNA declined. Both chronic and acute insulin normalized LPL activity and immunoreactive LPL protein, while only chronic insulin corrected the levels of LPL mRNA. No changes in the catalytic activity of LPL in heart were detected among the groups. Thus, diabetes and insulin treatment regulate LPL expression pretranslationally, translationally, and post-translationally, with tissue-specific differences apparent in the mechanisms involved. PMID- 1430199 TI - Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients. AB - We studied metabolic, polypeptide and genetic variation in eight glutaric acidemia type II (GA II) patients with electron transfer flavoprotein (ETF) deficiency. As measured by 3H-fatty acid oxidations in fibroblasts, beta oxidation pathway flux correlated well with clinical phenotypes. In six patients with severe neonatal onset GA II, oxidation of [9,10(n)-3H]-palmitate ranged from 2% to 22% of control and of [9,10(n)-3H]myristate, from 2% to 26% of control. Of two patients with late onset GA II, one had intermediate residual activities with these substrates and the other normal activities. Radiolabeling and immunoprecipitation studies revealed that three of the six neonatal onset GA II patients had greatly diminished or absent alpha- and beta-ETF subunits, consistent with a failure to assemble a stable heterodimer. Another neonatal onset patient showed normal synthesis of beta-ETF but decreased synthesis of alpha-ETF. Two neonatal onset and two late onset GA II patients showed normal synthesis of both subunits. Analysis of the pre-alpha-ETF coding sequence revealed seven different mutations in the six patients with neonatal onset GA II. The most common mutation was a methionine for threonine substitution at codon 266 found in four unrelated patients, while all the other mutations were seen in single patients. No mutations were detected in the two patients with late onset GA II. PMID- 1430200 TI - Homozygous 4.1(-) hereditary elliptocytosis associated with a point mutation in the downstream initiation codon of protein 4.1 gene. AB - We studied a 43 yr-old Spanish patient with homozygous 4.1(-) hereditary elliptocytosis. Any form of protein 4.1 was missing in the red cells. Spectrin and actin were slightly, yet significantly, diminished. Alterations appeared at the level of proteins 4.5 and 4.9. Glycophorin C was sharply reduced. The abnormal allele was associated with the -++-- haplotype (Pvu II, Bgl II, Bgl II, Pvu II, Pvu II). mRNA 4.1(-) had an apparently normal size but was diminished by about two-thirds. Because the abnormal phenotype pertained to the red cell, we sequenced the 4.1 cDNA regions that appear critical to this cell type. The ultimate change turned out to be a point mutation of the downstream translation initiation codon (AUG-->AGG). No disorders in other cell types could be related with certainty to the present 4.1(-) HE allele. PMID- 1430201 TI - Neuroendocrine mechanism of onset of puberty. Sequential reduction in activity of inhibitory and facilitatory N-methyl-D-aspartate receptors. AB - In humans and in several animal species, puberty results from changes in pulsatile gonadotropin-releasing hormone (GnRH) secretion in the hypothalamus. In particular, the frequency of pulsatile GnRH secretion increases at the onset of puberty, as can be shown by using hypothalamic explants of male rats of 15 and 25 d. Previous observations from us and others suggested that the initiation of puberty could involve a facilitatory effect of excitatory amino acids mediated through N-methyl-D-aspartate (NMDA) receptors. We found that GnRH secretion could be activated through NMDA receptors only around the time of onset of puberty (25 d). The aim of this study was to clarify why this activation did not occur earlier (at 15 d) and could no longer be observed by the end of puberty (at 50 d). We studied GnRH secretion in the presence of MK-801, a noncompetitive antagonist of NMDA receptors or AP-5, a competitive antagonist. We showed that, in the hypothalamus of immature male rats (15 d), a highly potent inhibitory control of pulsatile GnRH secretion in vitro was mediated through NMDA receptors. These data were confirmed in vivo because administration of the antagonist MK-801 (0.001 mg/kg) to immature male rats resulted in early pubertal development. Onset of puberty (25 d) was characterized by the disappearance of that NMDA receptor mediated inhibition, thus unmasking a facilitatory effect also mediated through NMDA receptors. During puberty, there was a reduction in activity of this facilitatory control which was no longer opposed by its inhibitory counterpart. We conclude that a sequential reduction in activity of inhibitory and facilitatory NMDA receptors provides a developmental basis for the neuroendocrine mechanism of onset of puberty. PMID- 1430202 TI - Blood volume and body fluid compartments in lambs with aortopulmonary left-to right shunts. AB - A left-to-right shunt is accompanied by an increased plasma and blood volume. Since this is likely realized through renin/aldosterone-mediated salt and water retention, other body fluid compartments may be changed too. Therefore, we studied blood volume and body fluid compartments by a single-injection, triple indicator dilution technique in nine 8-wk-old lambs with an aortopulmonary left to-right shunt (55 +/- 3% of left ventricular output; mean +/- SEM) and in 11 control lambs, 2.5 wk after surgery. Systemic blood flow was maintained at the same level as in control lambs, but the aortic pressure of the shunt lambs was lower. Blood volume in shunt lambs was larger than in control lambs (110 +/- 6 vs. 84 +/- 7 ml/kg, P < 0.001) through an increase in plasma volume, which correlated significantly with the magnitude of the left-to-right shunt (r = 0.81, P < 0.01). Red blood cell volume was equal to that of control lambs. Evidence was obtained that the increase in plasma volume was induced by a transient increase in renin (8.0 +/- 2.2 vs. 1.6 +/- 0.2 nmol.l-1.h-1; P < 0.02) and aldosterone (0.51 +/- 0.14 vs. 0.24 +/- 0.09 nmol/liter) concentrations. Interstitial water volume, however, was not significantly different from that in control lambs. The amount of intravascular protein was significantly higher than in control lambs (5.0 +/- 0.3 vs. 3.5 +/- 0.2 g/kg body mass, P < 0.001). There were no significant differences in intracellular and total body water volumes between the two groups. We conclude that the increased amount of intravascular protein confines the fluid retained by the kidneys to the vascular compartment. PMID- 1430203 TI - Importance of peripheral insulin levels for insulin-induced suppression of glucose production in depancreatized dogs. AB - It is generally believed that glucose production (GP) cannot be adequately suppressed in insulin-treated diabetes because the portal-peripheral insulin gradient is absent. To determine whether suppression of GP in diabetes depends on portal insulin levels, we performed 3-h glucose and specific activity clamps in moderately hyperglycemic (10 mM) depancreatized dogs, using three protocols: (a) 54 pmol.kg-1 bolus + 5.4 pmol.kg-1.min-1 portal insulin infusion (n = 7; peripheral insulin = 170 +/- 51 pM); (b) an equimolar peripheral infusion (n = 7; peripheral insulin = 294 +/- 28 pM, P < 0.001); and (c) a half-dose peripheral infusion (n = 7), which gave comparable (157 +/- 13 pM) insulinemia to that seen in protocol 1. Glucose production, use (GU) and cycling (GC) were measured using HPLC-purified 6-[3H]- and 2-[3H]glucose. Consistent with the higher peripheral insulinemia, peripheral infusion was more effective than equimolar portal infusion in increasing GU. Unexpectedly, it was also more potent in suppressing GP (73 +/- 7 vs. 55 +/- 7% suppression between 120 and 180 min, P < 0.001). At matched peripheral insulinemia (protocols 2 and 3), not only stimulation of GU, but also suppression of GP was the same (55 +/- 7 vs. 63 +/- 4%). In the diabetic dogs at 10 mM glucose, GC was threefold higher than normal but failed to decrease with insulin infusion by either route. Glycerol, alanine, FFA, and glucagon levels decreased proportionally to peripheral insulinemia. However, the decrease in glucagon was not significantly greater in protocol 2 than in 1 or 3. When we combined all protocols, we found a correlation between the decrements in glycerol and FFAs and the decrease in GP (r = 0.6, P < 0.01). In conclusion, when suprabasal insulin levels in the physiological postprandial range are provided to moderately hyperglycemic depancreatized dogs, suppression of GP appears to be more dependent on peripheral than portal insulin concentrations and may be mainly mediated by limitation of the flow of precursors and energy substrates for gluconeogenesis and by the suppressive effect of insulin on glucagon secretion. These results suggest that a portal-peripheral insulin gradient might not be necessary to effectively suppress postprandial GP in insulin-treated diabetics. PMID- 1430204 TI - Mesenchymal cells isolated after acute lung injury manifest an enhanced proliferative phenotype. AB - After acute lung injury, mesenchymal cells migrate into the alveolar airspace where they proliferate and deposit connective tissue macromolecules. Early in the disease process, inflammatory cell-derived trophic factors modulate these mesenchymal cell functions. However, in those patients who die, even as the inflammatory response abates, the fibroproliferative response continues, resulting in extensive intraalveolar fibrosis. We therefore hypothesized that lung mesenchymal cells obtained from individuals dying with acute alveolar fibrosis would manifest an enhanced proliferative capacity that was independent of persistent exogenous signals. To examine this hypothesis, the in vitro growth properties of mesenchymal cells prepared from patients dying with acute lung injury (n = 3) were analyzed in defined medium and compared with those of mesenchymal cells similarly prepared from patients dying with histologically normal lungs (n = 3). Isolates were characterized as mesenchymal cells by using morphological and immunohistochemical criteria. In accord with the hypothesis, mesenchymal cells isolated from lung-injured patients doubled within 3 d in the complete absence of exogenous peptide growth factors, reaching a saturation density of approximately 15 x 10(3) cells/cm2. As expected, lung mesenchymal cells from normal individuals failed to significantly increase in number. Consistent with this proliferative phenotype, the immediate early cell division cycle genes c-fos and c-jun were constitutively expressed in each cell strain prepared from injured lungs, but not in those from control lungs. The observed proliferative phenotype was stable through the fifth subcultivation of the cells. Despite these proliferative properties, three separate criteria indicated the mesenchymal cells from injured lungs were not transformed: normal karyotype; finite lifespan in vitro (9-10 subcultivations); and inability to disseminate in mice with severe combined immunodeficiency. These data support the hypothesis that mesenchymal cells manifest an enhanced proliferative state after acute lung injury. PMID- 1430205 TI - Cardiac contractile dysfunction during mild coronary flow reductions is due to an altered calcium-pressure relationship in rat hearts. AB - Coronary artery stenosis or occlusion results in reduced coronary flow and myocardial contractile depression. At severe flow reductions, increased inorganic phosphate (Pi) and intracellular acidosis clearly play a role in contractile depression. However, during milder flow reductions the mechanism(s) underlying contractile depression are less clear. Previous perfused heart studies demonstrated no change of Pi or pH during mild flow reductions, suggesting that changes of intravascular pressure (garden hose effect) may be the mediator of this contractile depression. Others have reported conflicting results regarding another possible mediator of contractility, the cytosolic free calcium (Cai). To examine the respective roles of Cai, Pi, pH, and vascular pressure in regulating contractility during mild flow reductions, Indo-1 calcium fluorescence and 31P magnetic resonance spectroscopy measurements were performed on Langendorff perfused rat hearts. Cai and diastolic calcium levels did not change during flow reductions to 50% of control. Pi demonstrated a close relationship with developed pressure and significantly increased from 2.5 +/- 0.3 to 4.2 +/- 0.4 mumol/g dry weight during a 25% flow reduction. pH was unchanged until a 50% flow reduction. Increasing vascular pressure to superphysiological levels resulted in further increases of developed pressure, with no change in Cai. These findings are consistent with the hypothesis that during mild coronary flow reductions, contractile depression is mediated by an altered relationship between Cai and pressure, rather than by decreased Cai. Furthermore, increased Pi and decreased intravascular pressure may be responsible for this altered calcium-pressure relationship during mild coronary flow reductions. PMID- 1430206 TI - Acquisition and synthesis of folates by obligate intracellular bacteria of the genus Chlamydia. AB - We undertook studies focused on folate acquisition by Chlamydia trachomatis L2, Chlamydia psittaci 6BC, and C. psittaci francis. Results from in situ studies, using wild-type host cells, confirmed that C. trachomatis L2 and C. psittaci 6BC are sensitive to sulfonamides whereas C. psittaci francis is resistant. In addition C. trachomatis L2 and C. psittaci francis were inhibited by methotrexate in situ whereas C. psittaci 6BC was not. In contrast to C. trachomatis, neither C. psittaci strain was affected by trimethoprim. Surprisingly our results indicate that all three strains are capable of efficient growth in folate depleted host cells. When growing in folate-depleted cells C. psittaci francis becomes sensitive to sulfonamide. The ability of all three strains to carry out de novo folate synthesis was demonstrated by following the incorporation of exogenous [3H]pABA into intracellular folates and by detecting dihydropteroate synthase activity in reticulate body crude extract. Dihydrofolate reductase activity was also detected in reticulate body extract. In aggregate the results indicate that C. trachomatis L2, C. psittaci francis, and C. psittaci 6BC can all synthesize folates de novo, however, strains differ in their ability to transport preformed folates directly from the host cell. PMID- 1430207 TI - Inhibition of lung epithelial cell proliferation by hyperoxia. Posttranscriptional regulation of proliferation-related genes. AB - The alveolar surface of the lung is a major target for oxidant injury. After injury, repair of the alveolar epithelium is dependent on the ability of epithelial type 2 (T2) cells to proliferate. The regulation of T2 cell proliferation and the effect of reactive oxygen (O2) species on this lung cell proliferation have not been well defined. To investigate this process we focused on the regulation of two late cell cycle genes, histone and thymidine kinase, in T2 cells and fibroblasts exposed in vitro to varying periods of hyperoxia (95% O2). Hyperoxia for 24 to 48 h arrested cell proliferation in a SV40T-immortalized T2 cell line we have developed and in primary and SV40T-immortalized lung fibroblasts. Despite the cessation of proliferation, histone and TK mRNA continued to be expressed at high levels; mRNA half-lives were markedly prolonged but neither protein was translated. Thus proliferation arrest induced by hyperoxia was associated with posttranscriptional control of at least two late cell cycle-related genes. This form of proliferation arrest is also seen when primary and SV40T-T2 cells but not fibroblasts are serum deprived, suggesting that T2 cells in vitro may be uniquely sensitive to alterations in their redox state and that these alterations in turn affect translational control of a subset of proliferation-related genes. PMID- 1430208 TI - New insights on the mechanism(s) of the dominant negative effect of mutant thyroid hormone receptor in generalized resistance to thyroid hormone. AB - Generalized resistance to thyroid hormone (GRTH) is a syndrome of hyposensitivity to triiodothyronine (T3) that displays autosomal dominant inheritance. The genetic defect commonly lies in the ligand-binding domain of one of the TR beta alleles. Since there are two major thyroid hormone receptor (TR) isoforms, TR alpha and TR beta, it is not known how the mutant receptor mediates a dominant negative effect. Previously, we showed that T3 caused dissociation of TR homodimers and TR alpha/TR beta dimers from several thyroid hormone response elements (TREs). Hence, we used the electrophoretic mobility shift assay to compare the effect of T3 on the DNA binding of mutant TR beta-1 (Mf-1) from a kindred with GRTH with normal TR beta. Mf-1 bound better as a homodimer than TR beta, but dissociated from DNA only at high T3 concentrations. Both receptors heterodimerized with nuclear auxiliary proteins. They also dimerized with TR alpha and with each other. Surprisingly, T3 disrupted the DNA binding of the Mf 1/TR isoform dimers. Thus, mechanisms for the dominant negative effect by mutant TRs likely involve either increased binding to TREs by mutant homodimers that cannot bind T3 (hence cannot dissociate from DNA) and/or the formation of inactive mutant TR/nuclear protein heterodimers. PMID- 1430209 TI - Induction of thrombospondin 1 by retinoic acid is important during differentiation of neuroblastoma cells. AB - Neuroblastoma, a malignant neoplasm that arises in the adrenal medulla or sympathetic ganglion, is one of the most common solid tumors of childhood. Reports that neuroblastomas spontaneously mature to form benign ganglioneuromas have prompted investigations into the efficacy of using agents that induce neuronal differentiation in the treatment of this malignancy. Retinoic acid is one agent in particular that has been shown to induce growth inhibition and terminal differentiation of neuroblastoma cell lines in vitro. Using the human neuroblastoma cell line SMH-KCNR, we have investigated the role of the extracellular matrix protein thrombospondin in retinoic acid induced neuroblastoma differentiation. Treatment with retinoic acid results in a rapid induction (within 4 h) of thrombospondin (TSP) message which is independent of intervening protein synthesis and superinducible in the presence of cycloheximide. This suggests that TSP functions as a retinoic acid inducible immediate early response gene. A concomitant increase in both cell associated and soluble forms of TSP protein can be detected within 24 h of retinoic acid treatment. A functional role for TSP in SMH-KCNR differentiation was established in experiments which showed that exposure to anti-TSP monoclonal antibodies delay retinoic acid differentiation for 48 h. At the time the cells overcome the effects of TSP inhibition, laminin production becomes maximal. Treatment of the cells with a combination of anti-TSP and antilaminin antibodies results in complete inhibition of differentiation. PMID- 1430210 TI - Animal cell mutants represent two complementation groups of peroxisome-defective Zellweger syndrome. AB - Generalized peroxisome-deficient disorders including cerebro-hepato-renal Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease are autosomal recessive diseases, where catalase-containing particles (peroxisomes) are morphologically absent. We previously isolated two Chinese hamster ovary (CHO) cell mutants (Z24 and Z65) that resemble the fibroblasts from patients with such diseases, in their defective peroxisome assembly (Tsukamoto, T., S. Yokota, and Y. Fujiki. 1990. J. Cell Biol. 110:651-660). Here we report isolation by the P9OH/UV method of a peroxisome-deficient CHO mutant, ZP92, of the third complementation group distinct from those of Z24 and Z65. Peroxisomal membrane ghosts were noted by immunochemical staining in all of the CHO mutants. Complementation analysis by cell fusion of the CHO mutants with cultured fibroblasts from patients with generalized peroxisomal disorders revealed that two CHO mutants (Z24 and ZP92) represent the human complementation groups, E (the same as group 1 in the U.S.) and C (the same as group 4), respectively. These CHO cell mutants are an apparently relevant animal cell model for studies on the molecular bases and primary defects of human peroxisome-deficient diseases. PMID- 1430211 TI - Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. AB - Enzymes within the P450IIIA (CYP3A) subfamily appear to account for significant "first pass" metabolism of some drugs in the intestine. To identify which of the known P450IIIA genes are expressed in intestine, enterocyte RNA was hybridized on Northern blots with synthetic oligonucleotides complementary to hypervariable regions of hepatic P450IIIA4, P450IIIA5, and P450IIIA7 cDNAs. Hybridization was detected only with the P450IIIA4-specific oligonucleotide. The identity of the hybridizing mRNA was confirmed to be P450IIIA4 by direct sequencing of a DNA fragment amplified from enterocyte cDNA by the polymerase chain reaction. To determine if enterocyte P450IIIA4 is inducible, biopsies of small bowel mucosa were obtained from five volunteers before and after they received 7d of treatment with rifampin, a known inducer of P450IIIA4 in liver. Rifampin treatment resulted in a five- or eightfold mean increase (P < 0.05) in the biopsy concentration of P450IIIA4 mRNA when normalized for content of sucrase isomaltase or intestinal fatty acid binding protein mRNAs, respectively. Rifampin also induced P450IIIA immunoreactive protein in enterocytes in each of the subjects, as judged by immunohistochemistry, and resulted in a 10-fold increase in P450IIIA4-specific catalytic activity (erythromycin N-demethylation) in the one patient studied. Our identification of inducible P450IIIA4 in enterocytes may in part account for drug interactions characteristic of P450IIIA4 substrates and suggests a strategy for controlling entry into the body of a major class of xenobiotics. PMID- 1430212 TI - Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles. AB - Hypertriglyceridemia is common in the general population, but its mechanism is largely unknown. In previous work human apo CIII transgenic (HuCIIITg) mice were found to have elevated triglyceride levels. In this report, the mechanism for the hypertriglyceridemia was studied. Two different HuCIIITg mouse lines were used: a low expressor line with serum triglycerides of approximately 280 mg/dl, and a high expressor line with serum triglycerides of approximately 1,000 mg/dl. Elevated triglycerides were mainly in VLDL. VLDL particles were 1.5 times more triglyceride-rich in high expressor mice than in controls. The total amount of apo CIII (human and mouse) per VLDL particle was 2 and 2.5 times the normal amount in low and high expressors, respectively. Mouse apo E was decreased by 35 and 77% in low and high expressor mice, respectively. Under electron microscopy, VLDL particles from low and high expressor mice were found to have a larger mean diameter, 55.2 +/- 16.6 and 58.2 +/- 17.8 nm, respectively, compared with 51.0 +/ 13.4 nm from control mice. In in vivo studies, radiolabeled VLDL fractional catabolic rate (FCR) was reduced in low and high expressor mice to 2.58 and 0.77 pools/h, respectively, compared with 7.67 pools/h in controls, with no significant differences in the VLDL production rates. In an attempt to explain the reduced VLDL FCR in transgenic mice, tissue lipoprotein lipase (LPL) activity was determined in control and high expressor mice and no differences were observed. Also, VLDLs obtained from control and high expressor mice were found to be equally good substrates for purified LPL. Thus excess apo CIII in HuCIIITg mice does not cause reduced VLDL FCR by suppressing the amount of extractable LPL in tissues or making HuCIIITg VLDL a bad substrate for LPL. Tissue uptake of VLDL was studied in hepatoma cell cultures, and VLDL from transgenic mice was found to be taken up much more slowly than control VLDL (P < 0.0001), indicating that HuCIIITg VLDL is not well recognized by lipoprotein receptors. Additional in vivo studies with Triton-treated mice showed increased VLDL triglyceride, but not apo B, production in the HuCIIITg mice compared with controls. Tissue culture studies with primary hepatocytes showed a modest increase in triglyceride, but not apo B or total protein, secretion in high expressor mice compared with controls. In summary, hypertriglyceridemia in HuCIIITg mice appears to result primarily from decreased tissue uptake of triglyceride-rich particles from the circulation, which is most likely due to increased apo CIII and decreased apo E on VLDL particles. the HuCIIITg mouse appears to be a suitable animal model of primary familial hypertriglyceridemia, and these studies suggest a possible mechanism for this common lipoprotein disorder. PMID- 1430213 TI - Interphase cytogenetics for the detection of the t(11;22)(q24;q12) in small round cell tumors. AB - Among the small round cell tumors differential diagnosis is particularly difficult for their undifferentiated or primitive character. In this mixed group of tumors, only the primitive neuroectodermal tumors, which include Ewing's sarcoma (ES), show the unique and consistent feature of the (11;22)(q24;q12) translocation, which can therefore be considered a hallmark of these neoplasias. We analyzed four primitive neuroectodermal tumor cell lines, one osteosarcoma cell line, and 11 patients by fluorescent in situ hybridization with cosmid clones 23.2 and 5.8, bracketing the t(11;22) at 11q24. Metaphase spreads from tumor cell lines, and from biopsy specimens of three patients with ES were analyzed. In the remaining eight patients comprising five ES, two small cell osteosarcomas and one chronic osteomyelitis, only nuclei preparations were available for analysis. We detected the t(11;22) in interphase nuclei of the four primitive neuroectodermal tumor cell lines, of three patients in which the karyotype demonstrated the translocation and in five cases of ES in which cytogenetic analysis had not been possible. Two cases of small cell osteosarcoma and one chronic osteomyelitis were also analyzed and were both normal with respect to the t(11;22). By analyzing cell lines and small round cell tumor samples by fluorescent in situ hybridization, we established that interphase cytogenetics is a rapid alternative to chromosomal analysis for the detection of the t(11;22) and represents an invaluable tool for the differential diagnosis of small round cell tumors. PMID- 1430215 TI - Regulation of insulin-like growth factor-I and its receptor in rat aorta after balloon denudation. Evidence for local bioactivity. AB - Local production of growth factors may play a major role in vascular repair after injury. We examined the regulation of insulin-like growth factor-I (IGF-I) and its specific membrane receptor in balloon-denuded rat aorta. Aortic IGF-I mRNA and radioimmunoassayable IGF-I content increased severalfold after balloon denudation with a peak at 7 d after injury. This coincided with a reciprocal 25% decrease in IGF-I receptor mRNA content and a 40% decrease in total 125I-IGF-I binding. Scatchard analysis indicated a single class of binding sites, with a decrease in receptor number at 7 d compared to control and no change in affinity. By in situ hybridization the predominant site of IGF-I expression in the normal and the denuded vessel wall was the medial smooth muscle cell. After denudation there was a relative decrease in IGF-I receptor mRNA in the medial cells as compared to the neointima, suggesting that the site of IGF-I action was predominantly in the medial layer. These data suggest that local expression and action of IGF-I are significant in the promotion of smooth muscle cell proliferation after arterial injury. PMID- 1430214 TI - Distinct sites of production and deposition of the putative cell death marker clusterin in the human thymus. AB - Clusterin is a multifunctional protein endowed with cell-aggregating, complement inhibitory, and lipid-binding properties. Since several studies have demonstrated highly increased clusterin gene expression in epithelial and nervous tissues regressing as a consequence of tissue involution and apoptotic cell death, clusterin is also considered as a specific marker of dying cells. To determine whether clusterin expression is also upregulated during thymocyte death occurring during the negative selection process we analyzed the cellular distribution of clusterin mRNA and protein by in situ hybridization and immunocytochemistry in the human thymus. We observed that the expression of clusterin mRNA was confined to cells present in the thymic medulla, concentrated mainly around Hassal's bodies. Immunostaining of adjacent sections with antikeratin Ab revealed that cells containing clusterin mRNA were predominantly epithelial. By contrast no clusterin mRNA was found in thymocytes by in situ hybridization and Northern blot analysis of total RNA from purified thymocyte populations. Clusterin protein colocalized with the membrane attack complex of complement and vitronectin in the center of the largest Hassal's bodies, but was not detectable by immunocytochemistry in or at the surface of epithelial cells. Our results demonstrate that clusterin gene expression does not take place in apoptotic thymocytes, and therefore that clusterin synthesis by the dying cell is probably not a prerequisite to its death. However, synthesis of clusterin by medullary epithelial cells may be related to their terminal differentiation, and, furthermore, its presence in Hassal's bodies raises the possibility that the secreted protein is involved in the disposal of cell debris resulting from thymocyte apoptosis. PMID- 1430217 TI - Distinct localization of collagenase and tissue inhibitor of metalloproteinases expression in wound healing associated with ulcerative pyogenic granuloma. AB - To examine the role of metalloproteinases in tissue remodeling associated with wound healing, we used in situ hybridization to localize the expression of collagenase and tissue inhibitor of metalloproteinases (TIMP) in samples of pyogenic granuloma. Strong hybridization for collagenase mRNA was detected in basal keratinocytes near the advancing edge of all ulcerative lesions, but no collagenase mRNA was seen in samples without ulceration. Distinct from the sites of collagenase expression, TIMP mRNA was detected in stromal cells and in cells surrounding proliferating vessels. No collagenase mRNA was found in the epidermis of healthy skin, although occasional stromal cells contained collagenase or TIMP mRNAs, and TIMP mRNA was detected in hair follicles and sebaceous glands. Our results suggest that basal keratinocytes adjacent to wounded epidermis are critically involved in matrix remodeling, much more so than adjacent or underlying dermal fibroblasts. Furthermore, as several reports have suggested, TIMP may play a role in angiogenesis. Finally, in contrast to findings from other models which indicate that collagenase and TIMP proteins are secreted by the same cells, our data also demonstrate that these proteins can be produced in vivo independently of each other. PMID- 1430216 TI - Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat. AB - To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces. PMID- 1430218 TI - Distribution of apolipoprotein(a) in the plasma from patients with lipoprotein lipase deficiency and with type III hyperlipoproteinemia. No evidence for a triglyceride-rich precursor of lipoprotein(a). AB - Lipoprotein(a) consists of a low-density lipoprotein containing apolipoprotein (apo) B-100 and of the genetically polymorphic apo(a). It is not known where and how lipoprotein(a) is assembled and whether there exists a precursor for lipoprotein(a). We have determined the phenotype, concentration, and distribution of apo(a) in plasma from patients with lipoprotein lipase (LPL) deficiency (type I hyperlipoproteinemia, n = 14), in apo E 2/2 homozygotes with type III hyperlipoproteinemia (n = 12) and in controls (n = 16). In the two genetic conditions, there is grossly impaired catabolic conversion of apo B-100 containing precursor lipoproteins to low-density lipoproteins. Considering apo(a) type, the plasma concentration of apo(a) was normal in type III patients but significantly reduced in LPL deficiency. Despite the defects in the catabolism of other apo B-containing lipoproteins, the distribution of apo(a) was only moderately affected in both metabolic disorders, with 66.7% (type I) and 74.7% (type III) being present as the characteristic lipoprotein(a) in the density range of 1.05-1.125 g/ml (controls 81.6%). The remainder was distributed between the triglyceride-rich lipoproteins (type I 12.4%, type III 8.5%, controls 4.7%) and the lipid-poor bottom fraction (type I 19.3%, type III 15.3%, controls 12.6%). In all conditions most apo(a) (57-88%) dissociated from the triglyceride rich lipoproteins upon recentrifugation and was recovered as lipoprotein(a). These data suggest that lipoprotein(a) is not generated from a triglyceride-rich precursor. Lipoprotein(a) may be secreted directly into plasma or may be formed by preferential binding of secreted apo(a) to existing low-density lipoprotein. PMID- 1430220 TI - Compartmentation of hexokinase in rat heart. A critical factor for tracer kinetic analysis of myocardial glucose metabolism. AB - Radiolabeled analogues of 2-deoxyglucose are widely used to trace glucose metabolism in cell cultures, whole organs, and intact animals, although kinetic differences in transport and phosphorylation between these compounds and glucose exist. The present studies were undertaken to determine the effects of insulin stimulation on the phosphorylation of 2-deoxyglucose compared to glucose in the intact, saline-perfused working rat heart. Rates of glucose utilization determined from tritiated glucose differed from rates estimated from the accumulation of [14C]2-deoxyglucose in a nonconstant manner when comparing rates in the absence or presence of physiologic levels of insulin (13 microU/ml). The fraction of monophosphorylated hexoses that was accounted for by [14C]2 deoxyglucose 6-phosphate was dramatically decreased in hearts perfused in the presence of insulin. Additionally, hexokinase activity associated with the mitochondrial fraction of tissue extracts was increased in hearts stimulated by insulin. While this redistribution of hexokinase to the mitochondria did not affect the apparent affinity constant for glucose, hexokinase bound to mitochondria exhibited an 8.5-fold decrease in the affinity for 2-deoxyglucose when compared with hexokinase present in the cytosolic fraction. The findings are consistent with an insulin-mediated preferential uptake and phosphorylation of glucose compared to deoxyglucose. The results also imply that the redistribution of hexokinase and the differential effect of insulin on its affinity for tracer and tracee are responsible for changes in the "lumped constant" (i.e., the correction factor used to equate 2-deoxyglucose to glucose uptake). These changes must be taken into account when regional myocardial glucose metabolism is assessed by the 2-deoxyglucose method. PMID- 1430219 TI - Natriuretic peptide receptor mRNAs in the rat and human heart. AB - Functional studies indicate that atrial natriuretic peptide (ANP), a member of the natriuretic peptide family, has direct effects on cardiac muscle cells. However, conventional ligand-binding studies designed to establish the presence of natriuretic peptide-binding sites in the heart have yielded conflicting results. There are discrepancies also between the latter and the receptor distribution predicted from the pattern of the mRNA transcripts localized by in situ hybridization. Here we have employed the technique of cDNA amplification with the polymerase chain reaction to confirm the presence of natriuretic peptide A, B, and C receptor mRNAs in rat and human cardiac tissue. In the rat heart, the distribution of the A and B receptor transcripts appears to be relatively homogeneous; in contrast, the C type mRNA is concentrated principally in the atria, with no difference between the left and right sides of the heart. A and B receptor DNA products were obtained after amplification of left, but not right, ventricular cDNA from the heart of a 16-yr-old male with cystic fibrosis; the yield of C receptor DNA was similar for both ventricles. If these mRNA transcripts are translated into functional receptors in the rat and human heart, ANP and the other natriuretic peptides may have direct effects on cardiac function, including regulation of natriuretic peptide release via a short feedback loop, modulation of contractility of the heart, or activation of cardiac reflexes. PMID- 1430221 TI - Alterations in the protein composition of maturing phagosomes. AB - We investigated the protein composition of J774-E clone macrophage phagosomes isolated at different stages of phagolysosome biogenesis. Phagosomes formed by internalizing antibody-coated Staphylococcus aureus for 3 min followed by chase for 0, 4, 9, or 15 min were isolated by density gradient centrifugation. Enrichment and purity of the phagosome preparations were quantitated by radiolabeled ligand recovery, enzyme markers, and electron microscopy. One dimensional SDS-PAGE analyses of the isolated phagosomes revealed virtually identical protein compositions. However, Western blot analyses with antibodies directed against selected proteins of known itineraries along the endocytic pathway demonstrated distinct differences in phagosome protein compositions. Accumulating within the maturing phagosome were the 31-kD subunit of the vacuolar proton pump, cathepsin D,beta-glucuronidase, the cation dependent mannose 6 phosphate receptor, and LAMP-1. Decreasing within the maturing phagosome were the FcII receptor, the mannose receptor, and alpha-adaptin. These results indicate that although the macrophage phagosome's total protein composition changes little during phagolysosome formation, the maturing phagosome both receives and eliminates, possibly by protein recycling, specific membrane and sequestered proteins. PMID- 1430222 TI - Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C. AB - Early diabetes mellitus is characterized by impaired responses to pressor hormones and pressor receptor downregulation. The present study examined the effect of elevated extracellular glucose concentrations on angiotensin II (AII) and arginine vasopressin (AVP) receptor kinetics in cultured rat vascular smooth muscle cells (VSMC). Scatchard analysis of [3H]AVP and 125I-AII binding to confluent VSMC showed that high glucose concentrations (20 mM) similarly depressed AVP and AII surface receptor Bmax but did not influence receptor Kd. This receptor downregulation was not reproduced by osmotic control media containing either L-glucose or mannitol. Receptor downregulation was maximal at a glucose concentration of 15-20 mM and required 24-48 h for a maximum effect. Normalization of the extracellular glucose concentration allowed complete recovery of AVP and AII binding within 48 h. Receptor downregulation was associated with depressed AVP and AII-stimulated intracellular signaling and cell contraction. High glucose concentrations induced a sustained activation of protein kinase C (PKC) in VSMC, which was prevented by coincubation with H-7. H-7 also markedly attenuated glucose-induced downregulation of AVP and AII receptors on VSMC. This study demonstrates a novel cellular mechanism whereby high extracellular glucose concentrations directly and independently downregulate pressor hormone receptors and their function on vascular tissue via glucose stimulated PKC activation. PMID- 1430223 TI - Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix. AB - Lipoprotein lipase enhances binding at 4 degrees C of human plasma lipoproteins (chylomicrons, VLDL, intermediate density lipoprotein, LDL, and HDL3) to cultured fibroblasts and hepG-2 cells and to extracellular matrix. Heparinase treatment of cells and matrix reduces the lipoprotein lipase enhanced binding by 90-95%. Lipoprotein lipase causes only a minimal effect on the binding of lipoproteins to heparan sulfate deficient mutant Chinese hamster ovary cells while it promotes binding to wild type cells that is abolished after heparinase treatment. With 125I-LDL, lipoprotein lipase also enhances uptake and proteolytic degradation at 37 degrees C by normal human skin fibroblasts but has no effect in heparinase treated normal cells or in LDL receptor-negative fibroblasts. These observations prove that lipoprotein lipase causes, predominantly, binding of lipoproteins to heparan sulfate at cell surfaces and in extracellular matrix rather than to receptors. This interaction brings the lipoproteins into close proximity with cell surfaces and may promote metabolic events that occur at the cell surface, including facilitated transfer to cellular receptors. PMID- 1430224 TI - Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids. AB - Leukemia inhibitory factor (LIF) has many biological actions which parallel those of IL-1, IL-6 and tumor necrosis factor-alpha, but its role in the pathogenesis of human disease is unknown. A specific radioreceptor competition assay capable of detecting LIF at concentrations above 1 ng/ml (45 pM) was developed. To identify disease states in which LIF might be involved, a cross-sectional survey of serum and body fluids from approximately 1,500 subjects with a variety of diseases was performed using the LIF radioreceptor competition assay. Serum LIF concentrations were transiently elevated (2-200 ng/ml) in six subjects with meningococcal or Gram-negative septic shock, and in a subject with idiopathic fulminant hepatic failure. Moderately elevated LIF concentrations (> 10 ng/ml) were detected in cerebrospinal fluid from subjects with bacterial meningitis, in effusions associated with pneumonia and peritonitis, and in amniotic fluid from a woman with chorioamnionitis. Low LIF concentrations (1-10 ng/ml) were present in synovial fluid from subjects with inflammatory arthritis, amniotic fluid from women in labor, and some reactive, chronic inflammatory and malignant effusions and cyst fluids, but rarely in transudates. These initial findings suggest that LIF might be involved in the pathogenesis of inflammation and septic shock. PMID- 1430225 TI - An amino acid polymorphism within the RGD binding domain of platelet membrane glycoprotein IIIa is responsible for the formation of the Pena/Penb alloantigen system. AB - The human Pena/Penb alloantigen system represents a naturally occurring polymorphism of human platelet membrane glycoprotein (GP) IIIa, and has previously been implicated in the onset of two important clinical syndromes, neonatal alloimmune thrombocytopenic purpura and posttransfusion purpura. To investigate the molecular basis of the polymorphism underlying the Pen alloantigen system, we used the polymerase chain reaction to amplify platelet derived GPIIIa mRNA transcripts. DNA sequence analysis of amplified GPIIIa cDNAs from nucleotides 161 to 1341 (encompassing amino acid residues 22-414) revealed a G526<==>A526 polymorphism that segregated precisely with Pen phenotype in twelve other individuals examined. This nucleotide substitution results in an Arg (CGA) to Gln (CAA) polymorphism at amino acid 143 of GPIIIa. Interestingly, this polymorphic residue is located within the putative RGD binding site (residues 109 171) of GPIIIa. Platelet aggregation patterns of a Penb/b individual, however, were nearly normal in response to all physiological agonists tested, indicating that this polymorphism does not grossly affect integrin function. Short synthetic peptides encompassing residue 143 were unable to mimic either the Pena or Penb antigenic determinants, suggesting that the Pen epitopes are dependent upon proper folding of the polypeptide chain. Finally, we constructed allele-specific recombinant forms of GPIIIa that differed only at amino acid residues 143. Whereas anti-Pena alloantibodies were able to recognize the Arg143 recombinant form of GPIIIa, anti-Penb antibodies were not. Conversely, anti-Penb alloantibodies were reactive only with the Gln143 isoform of the GPIIIa molecule. It thus appears that amino acid 143 of GPIIIa is not only associated with Pen phenotype, but specifically controls the formation and expression of the Pen alloantigenic determinants. PMID- 1430227 TI - Low molecular weight iron and the oxygen paradox in isolated rat hearts. AB - Little is known about changes in the amount of iron in the intracellular low molecular weight pool, which catalyzes the Fenton reactions during reperfusion after ischemia. In this study a new approach is presented to measure low molecular weight iron and it is applied to normal hearts during ischemia and to iron-loaded hearts during anoxia and reoxygenation. The results of this study show that (a) during ischemia in normal hearts a progressive 30-fold increase occurs in low molecular weight iron after 45 min of ischemia, whereas (b) during 45 min of anoxic perfusion the low molecular weight iron does not increase. This means that the reductive release from the storage protein ferritin is greatly enhanced by the acidification that occurs during ischemia. (c) Anoxic perfusion of iron-loaded hearts does increase low molecular weight iron and there is a further increase upon reoxygenation, which is prevented by (+)-cyanidanol-3. Based on these findings it is concluded that oxygen deprivation enhances the susceptibility of rat hearts to oxygen radicals by increasing the amount of catalytic, ferrous iron in the low molecular weight pool. PMID- 1430226 TI - Inhibition of smooth muscle cell proliferation in injured rat arteries. Interaction of heparin with basic fibroblast growth factor. AB - Heparin inhibits smooth muscle cell (SMC) proliferation after arterial injury by mechanisms that have yet to be defined. Since the initiation of SMC proliferation is mediated by basic fibroblast growth factor (bFGF), we have investigated the possibility that heparin inhibits SMC proliferation by displacing bFGF from the arterial wall. Using a rat carotid artery model of balloon catheter injury, we demonstrate that a bolus injection of heparin depletes the arterial wall of both systemically administered bFGF and of endogenous bFGF. Heparin, however, does not reduce the bFGF content of unmanipulated arteries. Further, a single injection of heparin given at the time of balloon injury reduces SMC proliferation by 55% but has no effect when given 6 h after injury. SMC proliferation induced in a denuded artery by injection of bFGF is inhibited almost completely by a bolus injection of heparin; however, pretreatment with a bolus of heparin does not prevent SMC from responding to a subsequent bolus of bFGF. These experiments suggest that heparin can inhibit SMC proliferation in part by removal of released bFGF from sites of injury. PMID- 1430228 TI - Role of transforming growth factor-beta in maintenance of function of cultured neonatal cardiac myocytes. Autocrine action and reversal of damaging effects of interleukin-1. AB - The three isoforms of transforming growth factor-beta (TGF-beta) have previously been implicated in embryonic development of the heart as well as in repair of myocardial damage after ischemia/reperfusion injury. TGF-beta 1 has also been localized intracellularly to both mitochondria and contractile filaments of cardiac myocytes, although its role in these structures has not been defined. We now report that exogenous TGF-beta stabilizes the beating rate of neonatal rat cardiac myocytes cultured on fibroblast matrix, and sustains their spontaneous rhythmic beating in serum-free medium. Moreover, using blocking antibodies to TGF beta, we show that endogenous TGF-beta secreted by these myocytes acts in an autocrine fashion to maintain their beating rate. In contrast, IL-1 beta, an inflammatory mediator secreted by immune cells during myocardial injury, inhibits the beating of cardiac myocytes, and TGF-beta can overcome this inhibition. The antagonistic effects of TGF-beta and IL-1 were not observed when the myocytes were cultured on gelatin, as compared to native fibroblast matrix. The data indicate that TGF-beta is an important regulator of contractile function of the heart and have significant implications for understanding cardiac physiology in health and disease. PMID- 1430229 TI - Enhancement of fibrinolysis in vitro by ultrasound. AB - The effect of ultrasound on the rate of fibrinolysis has been investigated using an in vitro system. Plasma or blood clots containing a trace label of 125I fibrin were suspended in plasma containing plasminogen activator and intermittently exposed to continuous wave 1-MHz ultrasound at intensities up to 8 W/cm2. Plasma clot lysis at 1 h with 1 microgram/ml recombinant tissue plasminogen activator (rt-PA) was 12.8 +/- 1.2% without ultrasound and was significantly (P = 0.0001) increased by exposure to ultrasound with greater lysis at 1 W/cm2 (18.0 +/- 1.4%), 2 W/cm2 (19.3 +/- 0.7%), 4 W/cm2 (22.8 +/- 1.8%), and 8 W/cm2 (58.7 +/- 7.1%). Significant increases in lysis were also seen with urokinase at ultrasound intensities of 2 W/cm2 and above. Exposure of clots to ultrasound in the absence of plasminogen activator did not increase lysis. Ultrasound exposure resulted in a marked reduction in the rt-PA concentration required to achieve an equivalent degree of lysis to that seen without ultrasound. For example, 15% lysis occurred in 1 h at 1 microgram/ml rt-PA without ultrasound or with 0.2 microgram/ml with ultrasound, a five-fold reduction in concentration. Ultrasound at 1 W/cm2 and above also potentiated lysis of retracted whole blood clots mediated by rt-PA or urokinase. The maximum temperature increase of plasma clots exposed to 4 W/cm2 ultrasound was only 1.7 degrees C, which could not explain the enhancement of fibrinolysis. Ultrasound exposure did not cause mechanical fragmentation of the clot into sedimentable fragments, nor did it alter the sizes of plasmic derivatives as demonstrated by SDS polyacrylamide gel electrophoresis. We conclude that ultrasound at 1 MHz potentiates enzymatic fibrinolysis by a nonthermal mechanism at energies that can potentially be applied and tolerated in vivo to accelerate therapeutic fibrinolysis. PMID- 1430230 TI - Retinoid protection against x-ray-induced chromatid damage in human peripheral blood lymphocytes. AB - Oral administration of isotretinoin (13-cis retinoic acid) was shown previously (Kraemer, K. H., J. J. DiGiovanna, A. N. Moshell, R. E. Tarone, and G. L. Peck. 1988. N. Engl. J. Med. 318:1633-1637) to reduce the frequency of skin cancers in xeroderma pigmentosum (XP) patients. The mechanism of protection was unclear. In the present study, x-ray-induced chromatid damage in PHA-stimulated blood lymphocytes from five XP patients receiving isotretinoin was approximately half that in blood samples from the same patients before or subsequent to treatment. The x-ray-induced chromatid damage in blood lymphocytes from a normal control was reduced significantly by cocultivation with blood or plasma from an XP patient receiving isotretinoin or by addition of 10(-6) M isotretinoin to cultures 1 h before x-irradiation. A similar reduction in x-ray-induced chromatid damage was reported previously by adding to the culture medium, mannitol, a scavenger of the free hydroxyl radical, or catalase, which decomposes hydrogen peroxide; both of these products are generated during ionizing radiation. The present observations suggest that isotretinoin acts as a scavenger of such radiation products, thereby providing protection against x-ray-induced chromatid damage. PMID- 1430231 TI - Immune complex processing in patients with systemic lupus erythematosus. In vivo imaging and clearance studies. AB - Abnormal processing of immune complexes (IC) may be important in the pathogenesis of systemic lupus erythematosus (SLE). The clearance of large soluble IC (comprising hepatitis B surface antigen (HBsAg)/anti-HBsAg) radiolabeled with 123I was examined in 12 normal subjects and 10 patients with SLE. IC localization was analyzed by static and dynamic gamma-scintigraphy. Initial IC clearance from blood was more rapid in patients (median t1/2 = 2.15 min) than normals (median t1/2 = 5.15 min) due to more rapid uptake in the liver. However, in the SLE group, up to 12% of complexes were released from the liver after 30-50 min. Splenic uptake of immune complexes was reduced in the patients and there was reduced ability to retain IC in this organ. Plasma complement levels and erythrocyte complement receptor type 1 numbers were reduced in the patients, resulting in defective opsonization of IC and reduced red cell binding in vivo. These observations support the hypothesis that IC handling is abnormal in SLE. PMID- 1430233 TI - Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene. AB - We have analyzed the nucleotide sequence of the androgen receptor from 22 unrelated subjects with substitution mutations of the hormone-binding domain. Eleven had the phenotype of complete testicular feminization, four had incomplete testicular feminization, and seven had Reifenstein syndrome. The underlying functional defect in cultured skin fibroblasts included individuals with absent, qualitative, or quantitative defects in ligand binding. 19 of the 21 substitution mutations (90%) cluster in two regions that account for approximately 35% of the hormone-binding domain, namely, between amino acids 726 and 772 and between amino acids 826 and 864. The fact that one of these regions is homologous to a region of the human thyroid hormone receptor (hTR-beta) which is a known cluster site for mutations that cause thyroid hormone resistance implies that this localization of mutations is not a coincidence. These regions of the androgen receptor may be of particular importance for the formation and function of the hormone-receptor complex. PMID- 1430234 TI - Novel Fc gamma receptor I family gene products in human mononuclear cells. AB - Unlike the human Fc gamma RII and Fc gamma RIII families, which exhibit considerable diversity at both the nucleic acid and protein levels, the human Fc gamma RI family has only a single recognized product expressed as a 70-kD cell surface receptor with high affinity for monomeric IgG (hFc gamma RIa1). Using both polymerase chain reaction-based amplification and Northern hybridization, we document multiple interferon-gamma-inducible hFc gamma RI RNA transcripts in human mononuclear cells and neutrophils. The sequences of two of these Fc gamma RI related transcripts indicate that they are alternatively spliced products of a second Fc gamma RI family gene, termed Fc gamma RIB. The cDNA derived from the larger of these transcripts, termed hFc gamma RIb1, encodes a surface molecule that is not recognized by Fc gamma RI specific monoclonal antibodies when transfected into COS-7 cells. Unlike the interferon-gamma-inducible hFc gamma RIA gene product, hFc gamma RIb1 does not bind monomeric IgG with high affinity. However, both hFc gamma RIa1 and hFc gamma RIb1 do bind aggregated human IgG. Previously unrecognized diversity within the hFc gamma RI family includes an interferon-gamma-inducible, putative low affinity Fc gamma receptor that may play an important role in the mechanism by which Fc gamma receptors participate in the humoral immune response. PMID- 1430232 TI - Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. Accelerated clearance of lipoproteins containing apolipoprotein B. AB - We have reported that transgenic mice overexpressing rat apo E shows marked reduction of plasma cholesterol and triglyceride levels due to the disappearance of VLDL and LDL. In this study, we investigated the metabolism of plasma lipoproteins in transgenic mice. After intravenous injection, the rates of clearance of 125I-VLDL and 125I-LDL were 3.0- and 2.4-fold greater in transgenic mice than in controls, respectively. Furthermore, clearance of chylomicron remnants estimated by oral retinyl palmitate-loading test was markedly enhanced in transgenic mice. The hepatic expression of LDL receptors by immunoblot analysis was similar in both groups. These data suggest that elimination of lipoproteins containing apo B was due to enhanced clearance of these lipoproteins enriched with apo E through hepatic LDL receptors. When fed a high cholesterol diet, controls showed twofold elevation of plasma cholesterol levels with marked increases in VLDL and LDL cholesterol on gel filtration chromatography. In contrast, cholesterol-fed transgenic mice showed resistance against these increases. High cholesterol feeding decreased the activity of hepatic LDL receptors and had no effect on enhancement of chylomicron remnant clearance in transgenic mice. Thus, overexpression of apo E facilitates metabolism of lipoproteins containing apo B presumably primarily via the LDL receptor pathway and possibly through an interaction with the chylomicron remnant receptor. PMID- 1430236 TI - Two distinct mechanisms for bilirubin glucuronide transport by rat bile canalicular membrane vesicles. Demonstration of defective ATP-dependent transport in rats (TR-) with inherited conjugated hyperbilirubinemia. AB - Bilirubin is conjugated with glucuronic acid in hepatocytes and subsequently secreted in bile. The major conjugate is bilirubin diglucuronide. Using sealed vesicles which are primarily derived from the canalicular (CMV) and sinusoidal (SMV) membrane vesicle domains of the plasma membrane of hepatocytes, we demonstrated that bilirubin glucuronides are transported by CMV by both ATP- and membrane potential-dependent transport systems. In CMV from normal rats, these processes are additive. In CMV from TR- rats, which have an autosomal recessively inherited defect in biliary secretion of nonbile acid organic anions, ATP dependent transport of bilirubin diglucuronide was absent whereas the membrane potential driven system was retained. Other canalicular ATP-dependent transport systems, which were previously described for organic cations and bile acids, are functionally retained in TR- rats. Our study indicates that bilirubin glucuronides are primarily secreted into the bile canaliculus by an ATP-dependent mechanism which is defective in an animal model of the human Dubin-Johnson syndrome. PMID- 1430235 TI - Human insulin-like growth factor I receptor function in pituitary cells is suppressed by a dominant negative mutant. AB - Hybrid receptors were studied in GC rat pituitary cells overexpressing either wild-type 950Tyr (WT) human insulin-like growth factor I (IGF-I) receptors or mutant human IGF-I receptors truncated at position 952 in the beta subunit transmembrane region (952STOP). 125I-IGF-I binding was increased in both 950Tyr (WT) (14-fold) and truncated human IGF-I receptor (952STOP) stable transfectants (50-fold), when compared to untransfected cells that contained endogenous rat IGF I receptors. Metabolic cell labeling followed by immunoprecipitation with monoclonal alpha and beta subunit-specific antibodies revealed the presence of hybrid rat/truncated human receptors, truncated transfected human receptors, and WT human IGF-I holotetramers. Both mutant and hybrid receptors were degraded slower than 950Tyr (WT) receptors (> 16 h). Despite their markedly increased ligand binding and prolonged receptor half-life, 952STOP transfectants failed to transduce the IGF-I signal to suppress growth hormone (GH). Also, they neither underwent autophosphorylation nor phosphorylated endogenous proteins. The expected suppression of GH by endogenous rat IGF-I receptors was completely abrogated in 952STOP transfectants (P < 0.001 compared to untransfected cells). Mutant 952STOP cells were therefore completely devoid of biological signaling to GH despite the presence of endogenous rat IGF-I receptors. Thus mutant IGF-I receptors block ligand-mediated endogenous rat IGF-I signaling by functioning as a dominant negative forming nonfunctional human/rat hybrid receptors. Defective IGF-I receptors may function therefore as dominant negative phenotypes which suppress normal receptor responses in pituitary cells. PMID- 1430237 TI - Development of concanavalin A-enzyme immunosorbent assay for glycated haptoglobin using polyclonal and monoclonal antibodies. AB - Two-site lectin-haptoglobin-enzyme immunosorbent assay (L-Hp-ELISA), is described. Haptoglobin binding to Concanavalin A, immobilized to polystyrene microtiter plate, was estimated by anti-haptoglobin polyclonal and monoclonal antibodies conjugated with horse-radish peroxidase. The range of haptoglobin binding to Concanavalin A, measured by the L-Hp-ELISA was 25 to 300 ng/ml using polyclonal, and 50 to 600 ng/ml using monoclonal anti-haptoglobin antibodies, respectively. PMID- 1430238 TI - Development of radioimmunoassay for TG-51, a new anti-ulcer drug, and its application. AB - A sensitive and specific radioimmunoassay for a new anti-ulcer drug TG-51 has been developed and applied to the evaluation of its pharmacokinetics in humans. The antiserum was raised in rabbits against an immunogen of N-Acetyl-TG-51 coupled to human serum albumin. The radioactive compound was prepared by acetylating TG-51 with 3H-Acetic anhydride. The separation of free and antibody bound N-Acetyl-TG-51 was performed by the dextran coated charcoal technique. TG 51 in biological fluids could be quantitatively converted to N-Acetyl-TG-51 prior to radioimmunoassay. This assay system made it possible to ascertain values of 3 ng/ml of TG-51 in plasma using 100 microliters of samples. Results were in good agreement with a high performance liquid chromatography method (HPLC), and the detection limit was raised 25 fold. The accuracy and repoducibility were also satisfactory. By use of this assay method, plasma levels of TG-51 could be determined after a single oral administration of clinical doses of human volunteers. PMID- 1430239 TI - Rapid assay for immune complex bound antigens from urine of cancer patients. AB - Concentrated urine from patients with various types of cancer was fractionated by S-500 gel filtration chromatography to yield high molecular weight (mw) immune complexes (IC) and lower mw immunoglobulin (Ig) fractions. Column fractions were assayed for the presence of IgM and IgG by immunoblot probing using anti-human IgM and anti-human IgG alkaline phosphatase conjugates. These results were used to define IC fractions (those from high mw S-500 fractions which were positive for immunoglobulin) and Ig fractions (those from medium mw S-500 fractions which were positive for immunoglobulin). Antigen components of high mw S-500 IC fractions were then determined by immunoblot probe using medium mw S-500 Ig fractions as the antibody probe (i.e. autoantibody). This method for identification of immune complex antigens has the potential to probe for tumor associated antigens, autoantigens, or foreign antigens from starting material which contains both immune complex and free immunoglobulin. PMID- 1430240 TI - An enzyme-linked immunosorbent assay (ELISA) for the detection of trypanosomal antigens in goat serum using a monoclonal antibody. AB - An IgM murine monoclonal antibody (MAb) TEA 1/23.3.4.6 raised against circulating trypanosome antigens was used in a sandwich ELISA to assay trypanosomal antigens in a trypanosome lysate preparation and in sera from goats infected with Trypanosoma brucei evansi. As little as 1.25 ug/ml of trypanosomal antigen could be detected by this assay. Following infection, trypanosomal antigens were first detected in goat serum 24 hours after the intravenous (i/v) or 6 days after the intramuscular (i/m) inoculation of trypanosome parasites. Antigen levels remained detectable during the course of infection. After treatment with diminazene aceturate, antigens dropped to undetectable levels between day 12 to 41, suggesting that this assay offers a promising approach to the diagnosis of African Trypanosomiasis. PMID- 1430241 TI - A rapid and sensitive heterogeneous immunoelectrochemical assay using disposable electrodes. AB - In this novel enzyme-tagged immuoelectrochemical assay, disposable carbon felt discs serve both as electrodes and as the heterogeneous solid phase. Antibodies are immobilized on the carbon felt via a diaminoalkane-biotin-avidin-biotin bridge. Alkaline phosphatase is used as a label. Bound antibodies are monitored by following the electro-oxidation of aminophenol, produced enzymatically from p amino-phenyl phosphate by the immobilized alkaline phosphatase at the electrode surface. A model system designed for determination of mouse IgG concentration yielded a calibration curve ranging from 10 pg/ml to 100 micrograms/ml. This assay can be performed rapidly and a single determination completed within 20 minutes. The system is useful also for rapid quantitation of a small number (approximately 80 organisms per ml) of bacteria. PMID- 1430242 TI - Monoclonal antibodies to porcine tumor necrosis factor alpha: development of an enzyme-linked immunosorbent assay. AB - Five hybridomas (4F4, 14H1, 9B4, 6E10, and 8G7) secreting antibodies to porcine tumor necrosis factor alpha (PTNF-alpha) were obtained from one fusion. Four of the 5 monoclonal antibodies (Mab) recognized recombinant PTNF-alpha (rPTNF-alpha) on western blot and were able to neutralize both rPTNF-alpha and native (released by porcine macrophages) PTNF (nPTNF-alpha, only 4F4, 14H1, and 9B4 tested for the neutralization of nPTNF-alpha) in vitro. A sandwich enzyme-linked immunosorbent assay (ELISA) for PTNF-alpha was developed using Mab 4F4 and purified rabbit polyclonal antibodies against PTNF-alpha. The test detected PTNF-alpha concentrations as low as 400 pg/ml and did not cross react with native porcine TNF-beta, recombinant human TNF-alpha, recombinant mouse TNF-beta or native mouse TNF-alpha. The Mabs and the ELISA should be useful for assessing PTNF-alpha levels in swine serum during disease processes and possibly for alleviation of toxic effects of TNF-alpha. PMID- 1430243 TI - Development of a direct and indirect chemiluminescence immunoassay for the detection of an organophosphorus compound. AB - The following study describes the development of two immunoassays for the semiquantitative determination of the organophosphorus compound methyl phosphonic acid, p-aminophenyl 1,2,2-trimethyl-propyl diester (MATP). These assays are a direct competitive, labelled-hapten, enzyme immunoassay and a competitive enzyme immunoassay with indirectly labelled antibody, both with luminescence determination of peroxidase. A camera luminometer was used to determine final signal strength. A constant light reaction was reached using luminol (5-amino-2,3 dihydro-1,4-phalazinedione), and by adding coumaric acid as an enhancer. A five minute interval was selected as exposure time. This phototechnical system makes a semiquantitative detection of MATP possible. The detection limits for both assays were at 10(-6)mol/l MATP. With the help of a microtiter luminometer (reader) the detection limit was reduced to 5 x 10(-8) mol/l MATP, by measuring the real intensity of the chemiluminescence signal. PMID- 1430244 TI - Non-specific immunoglobulin interactions may lead to false-positive results in assays for human anti-mouse monoclonal antibodies (HAMA). AB - This abstract demonstrates that non-specific immunoglobulin interactions, of the F(ab')2 region and Fc piece of human IgG may lead to false-positive results in patients being monitored for naturally occurring (pre-existing) or induced human anti-mouse monoclonal Ig antibodies (HAMA). Patient sera tested before administration of murine monoclonal antibodies for immunoscintography or immunotherapy showed 'positive' results when screened by specific ELISA for the presence of pre-existing antibodies to murine immunoglobulin. However, only serum from a patient which had previously received murine monoclonal antibody for immunotherapy, was it possible to show specificity by competitive inhibition. Thus, the use of competitive inhibition by specific antigen (mouse Ig isotype/subtype), sera positive for HAMA or pre-existing HAMA can be distinguished from false-positive reactions. PMID- 1430245 TI - Production and utilisation of antibodies directed against oestrone sulphate using specific hapten synthesis. AB - Oestrone-3-sulphate (E13S) is an important metabolite of oestrone. Studies in cattle had previously shown that it is synthesised in the gravid uterus by the foetus, but not by the corpus luteum. Progesterone measurement in milk by radioimmunoassay (RIA) is routinely carried out in some laboratories as a pregnancy test for cattle. The major drawback of progesterone measurement in milk, by RIA, as a pregnancy test was the failure to detect the lack of conceptus in those cows where early embryonic death had occurred but the corpus luteum still persisted thereby giving false positive results. We have developed a direct RIA for E13S by raising antibodies to an immunogen prepared from a specific hapten synthesised by an unambiguous chemical synthesis. The sensitivity of the RIA in milk was found to be 0.368 nmol/l. The levels of E13S in non-pregnant cows are undetectable but during a viable pregnancy, the levels are elevated to greater than 0.40 nmol/l by day 100. There was no cross-reactions in the assay with any free oestrogens. The measurement of this metabolite of oestrone promises to provide an accurate marker for the detection of a viable conceptus in cattle. PMID- 1430246 TI - Technical note: is there a season for iodinating relaxin? AB - We report a loss of antibody binding in our porcine relaxin radioimmunoassay that has occurred during the coldest periods of the past three winters. We do not know the reason for this seasonal variation but we have eliminated cold deterioration of the iodide used for radioiodination and equipment failures as explanations. PMID- 1430247 TI - The prediction and control of behavior revisited: a review of the matching law. AB - Experimental research conducted over the past 3 decades in relation to behavioral allocation and choice, collectively known as matching law research, is analyzed in this paper. The importance of the matching law for areas ranging from experimental to clinical psychology and psychiatry is discussed in relation to empirical findings that bear upon the validity and utility of the matching law for both the prediction and control of human behavior as well as for psychological and scientific inquiry in general. PMID- 1430248 TI - Cognitive therapy: a misunderstanding of B. F. Skinner. PMID- 1430249 TI - Attitudes of Arabic psychology students toward behavior modification. AB - Several American studies have investigated attitudes toward behavior modification. As there are no data on perceptions of this approach in other countries, this study was undertaken to examine such attitudes in Arab countries. The attitudes of 102 undergraduate psychology students at the University of Jordan were assessed. The results showed that behavior modification is favorably received. No significant differences were found between male and female students, or among second, third, and fourth year students. However, significant differences were found between students who had taken a behavior modification course and those who had not. PMID- 1430250 TI - Skin temperature biofeedback: evaluation of non-clinical children's responses. AB - The present study evaluated the extent to which children are able to learn to increase skin temperature with biofeedback training. Forty-nine children (ages 7 16) were randomly assigned to either standard biofeedback, novel biofeedback or control groups, which met for 16, 16, and 5 sessions, respectively. Results indicated children in the novel biofeedback group significantly increased their skin temperature as compared with the control group. The biofeedback groups exhibited significant skin temperature control during feedback. Results provide normative data on what to expect from children receiving skin temperature biofeedback. PMID- 1430251 TI - Behavioral intervention to reduce water intake in the syndrome of psychosis, intermittent hyponatremia, and polydipsia. AB - We describe a non-intensive behavioral intervention using an A-B design with extended follow-up on an open psychiatric unit to reduce water intake in a 52 year-old man with the syndrome of psychosis, intermittent hyponatremia, and polydipsia. A reinforcement schedule contingent upon weight gain secondary to water intake was employed. Mean diurnal weight gain was 7.1 pounds during a 23 week baseline which dropped to 4.1 pounds following 23 weeks of treatment and at a 1-year follow-up. Estimated fluid consumption dropped from 10 liters to 4 liters daily and incidents of hyponatremia decreased by 62%. PMID- 1430252 TI - The efficacy of rational emotive therapy in adults: clinical fact or psychometric artifact? AB - The efficacy of Rational-Emotive Therapy (RET) in reducing maladjustment, while insistently touted by its advocates, has not been unambiguously demonstrated in outcome research. Previous reviews have generally been quite partisan and subjective, and have not reflected available research. The object of the present review was to determine the extent to which RET significantly improved adjustment of adult subjects on different outcome measures in comparison with wait-list, placebo, and other treatment conditions. In 75 outcome reports, RET was effective in only about 25% of comparisons. Its main effect was to reduce scores of self reported irrationality and dysphoria. Little change was noted in behavioral measures. The few comparisons favoring RET could be attributed to psychometric artifacts rather than to the reduction of irrational beliefs. PMID- 1430253 TI - The changing practice of pathology. PMID- 1430254 TI - Bone marrow histology. 3: Value of bone marrow core biopsy in acute leukaemia, myelodysplastic syndromes, and chronic myeloid leukaemia. PMID- 1430255 TI - Monoclonal antibody JC1: new reagent for studying cell proliferation. AB - AIM: To characterise a newly developed mouse monoclonal antibody JC1 which recognises a nuclear antigen present in proliferating cells in normal tissues and neoplastic lesions, and which is absent in resting cells. METHODS: The methodology was established using a representative range of frozen sections from normal tissues and from certain tumours which were immunostained with antibodies Ki67 and JC1. The molecular weight of the antigen recognised by JC1 was obtained by western blot analysis and this was compared with that of Ki67. IM-9 cell lysates containing Ki67 derived plasmids were also tested with JC1 antibody. RESULTS: Biochemical investigation indicated that the antigen recognised by JC1 gives two molecular weight bands of 212 and 123 kilodaltons, which is distinct from the well characterised anti-proliferation monoclonal antibody Ki67 (395-345 kilodaltons). In addition recombinant Ki67 protein is not recognised by JC1. Immunohistological reactivity was seen in areas known to contain numerous proliferating cells such as lymphoid germinal centres, splenic white matter, cortical thymocytes and undifferentiated spermatogonia. In tumours many cells from adenocarcinomas, oat cell carcinomas, squamous cell carcinomas of lung, and seminomas were labelled by JC1 with a distribution and proportion similar to that seen with Ki67. In normal tissues the only apparent difference was in testis where JC1 stained a considerably greater number of cells than Ki67. In all cases studied the new antibody showed nuclear reactivity only. JC1 did not show any cytoplasmic crossreactivity with squamous cells as is frequently seen with Ki67. CONCLUSION: Antibody JC1, which recognises a nuclear antigen present in proliferating cells, should provide a useful adjunct to Ki67 as a marker of proliferation especially in those cases such as squamous cell carcinomas where a Ki67 index cannot be determined. PMID- 1430256 TI - Demonstration of HIV-1 infected cells in human placenta by in situ hybridisation and immunostaining. AB - AIMS: To show the presence of HIV infected cells in the placentas and membranes exposed to HIV during pregnancy, and to trace the possible transmission routes from mother to fetus. METHODS: Twenty three therapeutic abortions and 11 term placentas were investigated for the presence of HIV antigen by immunostaining with HIV core protein specific antibodies and HIV nucleic acids by in situ hydridisation (ISH) with a 35S-labelled HIV specific RNA probe. RESULTS: HIV antigen as well as HIV RNA positive cells were rarely found in placental tissue and membranes. In therapeutic abortions HIV antigen was shown in 10 out of 23 placentas, HIV RNA in two. HIV antigen was detected in five out of 11 term placentas and HIV RNA in two. Infected cell types comprised syncytiotrophoblasts, Hofbauer cells, amnionic epithelium, chorionic macrophages as well as maternal lymphocytes in the intervillous space and decidua. CONCLUSION: These data suggest that the transmission routes are: (1) a haematogenous route from the maternal intervillous space to villous stromal cells; (2) from chorion laeve to amnionic fluid and vice versa. Two additional transmission routes are partly suggested by the data: (1) in early gestation by direct extension from basal decidua to budding trophoblastic cells; (2) from the capsular decidua to chorion laeve and chorionic plate, entering the fetal circulation via the small veins. PMID- 1430257 TI - Cell sizing in chronic lymphoproliferative disorders: an aid to differential diagnosis. AB - AIMS: To determine if leucocyte volume distribution analysis (LVDA), obtained using a Coulter Counter Model S Plus IV, can be used to aid differentiation of chronic lymphoproliferative disorder (CLPD) subtypes. METHODS: Mean lymphocyte volume and lymphocyte distribution width were measured on each patient (n = 90) using a hard copy of an amplified LVDA histogram. The mean lymphocyte volume was taken as the mean of the values on either side of the peak at half maximum height. The lymphocyte distribution width was taken as the range of cell values between the two values used to calibrate the mean lymphocyte volume. A template showing typical histograms from commonly occurring CLPD was also produced on an acetate sheet. This was used to examine the histogram from each new patient to evaluate its usefulness as an alternative to the calculation of mean lymphocyte volume and lymphocyte distribution width. RESULTS: Mean lymphocyte volume and lymphocyte distribution width were significantly higher in B cell lymphocytic leukaemia of mixed cell type (B CLL/PL), B cell non-Hodgkin's lymphoma with peripheral blood spill, hairy cell leukaemia and T cell prolymphocytic leukaemia than in B cell chronic lymphocytic leukaemia (B CLL). The mean lymphocyte volume, but not the lymphocyte distribution width, was also significantly higher in T cell chronic lymphocytic leukaemia than in B CLL. The template gave an immediate preliminary indication of possible subtype(s) of disorder and could be used as an alternative to measurement of mean lymphocyte volume and lymphocyte distribution width. CONCLUSIONS: Electronic haematology analysers producing an LVDA provide a useful, cost effective cell sizing analysis which can aid the differentiation of subtypes of CLPD. PMID- 1430258 TI - ICAM-1 expression in renal disease. AB - AIM: To determine the role of intercellular adhesion molecule-1 (ICAM-1) in immune mediated damage in glomerulonephritis, and whether its expression correlates with disease activity. METHODS: Fifty three renal biopsy specimens from a range of non-immune renal disease and low grade and high grade glomerulonephritides were stained with ICAM-1. Positivity was assessed in the tubules. Tubular damage and accompanying interstitial inflammation were also noted. The ICAM-1 positivity in damaged and undamaged tubules was correlated with the three groups of renal disease. RESULTS: ICAM-1 positivity in undamaged tubules was observed in glomerulonephritis, and this showed a strong correlation with disease activity. In contrast, ICAM-1 positivity on damaged tubules correlated with evidence of chronic tubular damage, and was seen in a large proportion of cases, regardless of the underlying disease. There was no correlation between ICAM-1 positivity and a local lymphocytic infiltrate. CONCLUSION: ICAM-1 probably has an important role in the pathogenesis of glomerulonephritis. Its expression may be secondary to cytokines released by cells participating in the glomerular damage. As these cytokines also influence tubule function, tubular ICAM-1 expression may be a marker of the extent of tubular disturbance in glomerulonephritis. PMID- 1430259 TI - Nucleolar organiser regions (AgNORS) in anal intraepithelial neoplasia and invasive anal squamous cell carcinoma. AB - AIM: To evaluate the usefulness of counting nucleolar organiser region associated proteins (AgNORs) in the management of anal squamous neoplasia. METHOD: Using a silver staining technique for NOR associated proteins, 32 routinely processed paraffin wax embedded sections of anal epithelium were assessed. These consisted of normal anal epithelium (n = 9), anal intraepithelial neoplasia (AIN) grades I (n = 5), and III (n = 13), and invasive squamous neoplasia of the anus (n = 5). RESULTS: The median AgNOR counts for every 100 cells are as follows: normal anal epithelium 2.15 (95% CI 1.89-3.94); AIN I 3.21 (95% CI 2.89-7.14); AIN III 4.32 (95% CI 4.00-8.10); and invasive squamous cell carcinoma of the anus 5.51 (95% CI 2.48-10.62). There were significant differences between AgNOR counts in anal cancer and normal epithelium (p < 0.05; Mann-Whitney U test)), AIN III and normal anal epithelium (p < 0.005), and AIN III and AIN I (p < 0.05). No significant differences were observed between AIN I and normal anal epithelium, anal cancer and AIN I, and anal cancer and AIN III. There was a considerable degree of overlap among the different groups. CONCLUSIONS: Despite the strong association between AgNOR values and degree of dysplasia, the variability within pathological grade may preclude the adoption of this technique on its own as a prognostic indicator. It may, however, be useful in conjunction with other markers of neoplastic growth such as c-myc oncogene amplification or overexpression as a marker of disease progression in AIN and invasive anal squamous cell cancer. PMID- 1430260 TI - Nasopharyngeal carcinoma in situ in nasopharyngeal carcinoma. AB - AIMS: To assess the presence of carcinoma in situ (CIS) in patients with nasopharyngeal carcinoma (NPC) and to see if the number of biopsy sites facilitates detection of CIS. METHODS: Formalin fixed, paraffin wax embedded biopsy specimens (n = 285) from 187 patients with NPC in 1987 were studied for the presence of CIS as well as for the histological assessment of the subtype of CIS. RESULTS: Fifteen (8.0%) patients had CIS, representing 8.3% of all new patients with NPC and 11.6% of patients with persistent disease or relapse. CIS was undifferentiated or poorly differentiated, no cases of well differentiated squamous cell CIS were identified. There was no significant difference in the incidence of CIS when multiple endoscopic biopsy specimens were taken rather than single forceps biopsy specimens. CONCLUSIONS: CIS can only be identified in a few patients with NPC largely because of late presentation with advanced disease at the time of diagnosis and the focal nature of the dysplastic process. The presence of dysplasia in relapses of NPC suggests that these tumours may be second growths rather than regrowths of a primary tumour. PMID- 1430261 TI - Modified latex agglutination test for antibodies to Toxoplasma gondii in eluates from Guthrie cards. AB - AIMS: To determine whether the Eiken particle agglutination test could be modified to make it sufficiently sensitive to screen blood samples collected on Guthrie cards for the presence of antibodies to Toxoplasma gondii; to evaluate the specificity of the modified system; and to compare seroepidemiological data on the prevalence of T gondii in pregnant women. METHODS: Simulated dried blood spots were prepared from sera from pregnant women booking for antenatal care. Eluates from the simulated dried blood spot cards and sera were tested in parallel using the modified test (1 in 5 dilution of latex) and the standard assay (neat latex particles) and endpoints determined. Guthrie card eluates, from neonates in three Thames regions, were then tested using the modified test. RESULTS: The modified test produced a 4.21-fold increase in antibody titre in 85 sera when tested in parallel with the standard test. Eluates of 168/170 from simulated dried blood spots derived from seropositive patients gave a positive result in the modified test. The two eluates which gave a negative result were derived from patients with an equivocal titre of 1/16 in the standard serum test. Of the eluates derived from serum negative patients all 103 were negative at a dilution of 1 in 4 in the modified test. The seroprevalence of antibodies to T gondii in pregnancy was 21.8% using the standard test. A similar value of 20.5% was obtained when dried blood spots from neonates in a similar region of London were tested by the modified test. CONCLUSIONS: The modified Eiken Toxo-reagent test is sensitive, simple, and economic for screening large numbers of dried blood spots. The procedure could be easily semiautomated and the technique applied to the mass screening of neonatal blood samples collected on Guthrie cards to determine the seroprevalence of T gondii in pregnant women. PMID- 1430262 TI - Use of the polymerase chain reaction to detect Toxoplasma gondii in human blood samples. AB - AIMS: To assess the value of detecting Toxoplasma gondii in human blood samples using the polymerase chain reaction (PCR). METHODS: Blood samples in lithium heparin were examined from 34 patients with suspected toxoplasmosis, and six healthy volunteers with or without the addition of doubling dilutions of toxoplasma tachyzoites. Products of a nested PCR, using oligonucleotide primers of the B1 gene, were analysed by electrophoresis and stained by ethidium bromide. The primary product was 194 base pairs in length; the nested products were 160 or 97 base pairs. RESULTS: When toxoplasma tachyzoites were added to the leucocytes of six different volunteers, eight to 16 parasites were detected by nested PCR in one experiment and one to four parasites in eight experiments. All nine experiments were negative in samples without added tachyzoites. Of 34 patients, PCR was negative in 13 with recent lymphadenopathy; nine with persisting IgM, including two pregnant patients; four with reactivated infection due to immunodeficiency; and five with no evidence of active infection. Positive PCR results were found in three patients with reactivated infection. There was only one discrepancy between PCR and animal culture results; this was in an immunocompromised patient with a positive PCR and negative culture. CONCLUSIONS: The PCR technique was rapid, sensitive, and specific in human blood samples. Negative PCR results in patients with persisting IgM suggested that the fetus was not at risk, or that treatment was not indicated in myalgic encephalomyelitis like illness. PCR results in immunocompromised patients permitted appropriate management--no treatment if negative, treatment if positive. PMID- 1430263 TI - Laboratory examination for Cryptosporidium spp in Scotland. AB - AIMS: To ascertain the present practices of Scottish microbiological laboratories for examining faecal samples for Cryptosporidium spp and to compare these with practices elsewhere. METHOD: A questionnaire was circulated to all 35 Scottish NHS bacteriological laboratories, where human stool samples are subjected to routine microbiological examination, to determine current laboratory testing methods and selection criteria used to examine faecal specimens for Cryptosporidium spp. RESULTS: All laboratories responded, of which the first began testing in 1984 and the last in 1990. At 15 sites all diagnostic stool samples submitted are routinely examined for Cryptosporidium spp. Elsewhere, selection criteria, principally based on age, specific request, and foreign travel, are used. The age distribution of Scottish cases differed significantly from that of the PHLS study of 16 laboratories (p < 0.001), probably as a result of the selection criteria used. The phenol-auramine staining procedure is used by 19 laboratories, with modified Ziehl-Neelsen staining used by 14 laboratories; eight used a second, confirmatory method. CONCLUSIONS: Currently applied selection criteria for examination of stools for Cryptosporidium in Scotland do not accord with published epidemiological data. Specimen selection based on age of patient and stool consistency may lead to cases of public health importance being missed. Nationally agreed criteria for testing of human samples based on epidemiological evidence are required. PMID- 1430264 TI - Antithrombin III deficiency and cerebrovascular accidents in young adults. AB - A young man with antithrombin III (AT-III) deficiency sustained a cerebellar venous infarct and recovered following treatment with AT-III concentrate. A family study showed that other members were affected. AT-III deficiency in this family was found to be due to a new variant AT-III TRURO 1. Young patients with strokes should be screened for thrombophilia. PMID- 1430265 TI - Tissue artefacts caused by sponges. AB - Artefacts which occur during the processing of small biopsy specimens can cause sufficient tissue distortion to impair interpretation and can be a considerable source of nuisance. Triangular artefacts were noted in renal and liver biopsy specimens which were caused by foam sponges in embedding cassettes. Scanning electron microscopic examination of the sponges showed they comprised a mesh of scimitar-shaped rigid spikes which closely match the artefacts seen in the tissues. PMID- 1430266 TI - Alternative method of sampling placentas for the assessment of uteroplacental vasculature. AB - A new method for the taking and embedding of placental blocks to obtain maximum information regarding the uteroplacental vasculature was developed. This method involves taking en face blocks of the basal plate of the placenta. Results show that normal and abnormal maternal vessels are clearly delineated. In addition to conventional full thickness blocks, which provide information about the chorionic plate such as inflammation and meconium pigment uptake, and about the parenchyma in the other zones remote from the basal plate of the placenta, it is recommended that en face blocks be taken for histological assessment of the placenta. PMID- 1430267 TI - Tubulovillous adenoma arising 30 years after ileocystoplasty. AB - The possibility of recurrent colonic metaplasia occurring as a complication of pelvic ileal pouches after ileo-rectal anastomosis has been raised. Several reports have documented malignant bladder tumours developing in patients many years after an ileocystoplasty. The case of a 50 year old man, who developed a tubulovillous adenoma in the ileal patch 30 years after an ileocystoplasty had been performed to enlarge a tuberculous shrunken bladder, is reported. The adjacent small intestinal mucosa showed features suggestive of colonic metaplasia. PMID- 1430268 TI - Abnormal haemoglobin electrophoresis caused by BW 12C. AB - BW 12C, a substituted benzaldehyde, stabilises haemoglobin in the oxy conformation and has attracted interest as an anti-sickling agent. The drug causes a left shift in the oxygen saturation curve and may induce tumour anoxia and enhance the effect of cytotoxic drugs. During clinical trials in patients with cancer abnormal bands on haemoglobin electrophoretic strips were observed. This made correct diagnosis of abnormal haemoglobins impossible. Solubility tests for sickling disorders (Itano) also proved unreliable. PMID- 1430269 TI - Diagnosis of toxoplasma infection in cardiac transplant recipients using the polymerase chain reaction. AB - Cardiac biopsy samples taken from transplant recipients around the time of primary toxoplasma infection were investigated by conventional histology and amplification of the P30 gene of Toxoplasma gondii by the polymerase chain reaction (PCR). Toxoplasma was detected more frequently by PCR than histology which may reflect the enhanced sensitivity of the former technique. Further studies are required to determine the optimal amount of tissue which should be examined by each technique and to develop a PCR assay capable of distinguishing between quiescent infection and active toxoplasmosis. PMID- 1430270 TI - Renal AA amyloidosis in a patient with Bence Jones proteinuria and ankylosing spondylitis. AB - A patient with a 10 year history of monoclonal gammopathy of undetermined significance and Bence Jones proteinuria, and a 44 year history of ankylosing spondylitis, developed a nephrotic syndrome secondary to renal amyloidosis. Clinically the amyloidosis was ascribed to Bence Jones proteinuria rather than to the burnt out ankylosing spondylitis. However, histochemical and immunofluorescence staining techniques used to type the amyloid fibrils showed AA amyloidosis, implicating ankylosing spondylitis rather than monoclonal gammopathy as the underlying cause of the patient's systemic amyloidosis and consequent nephrotic syndrome. It is recommended that immunostaining of amyloid become a routine procedure to detect occult or apparently inactive disease. PMID- 1430271 TI - Lobular carcinoma in a mammary hamartoma. AB - Mammary hamartomas are uncommon breast lesions, sometimes presenting as mammographic abnormalities which require pathological clarification. Previous cases have all been benign. A unique case of mammary hamartoma containing atypical lobular hyperplasia (ALH), lobular carcinoma in situ (LCIS), and foci of microinvasive lobular carcinoma is presented. The need for adequately sampling macroscopically innocuous breast lesions is emphasised. PMID- 1430272 TI - Screening of urinary tract infections by ELISA. PMID- 1430273 TI - The action of vitamin B12. PMID- 1430274 TI - c-erb-B-2 expression in male breast carcinoma. PMID- 1430275 TI - Glove puncture in the post mortem room. PMID- 1430276 TI - Risk of inhaling cyanide during necropsy examination. PMID- 1430277 TI - The teaching of death certification. PMID- 1430278 TI - A computer-assisted method for making linear radiographic measurements using stored regions of interest. AB - Accurate detection of changes in alveolar bone height requires radiographic measuring methods with a reliability of standard deviation (SD) of 0.15 mm or better. No periodontal digital imaging system has reached this reliability, although 3 analogue methods have achieved this goal. However, existing linear methods are time-consuming, difficult to use, unsuitable for measuring all possible (unsharp) anatomical sites and do not provide a confidence estimate for sites of change observed in serial standardized films. A rapid computer-assisted method using stored image regions of interest (ROI) has been developed which allows retest measurements for all possible sites and automatically calculates a 90%, 95%, 98%, or 99% confidence threshold value, derived from duplicate measurement variation, for sites of apparent crest height change. 28 examiners, with minimal training in operating the system, measured 14 different cement enamel junction to crest height distances from a standard bitewing image, with and without the ROI method. The measurements were repeated 4 weeks later. 13/14 sites achieved an intra-examiner SD threshold of less than or equal to 0.15 mm with the ROI method but 0/14 without. A higher inter-examiner SD threshold of less than or equal to 0.22 mm was achieved for 13/14 sites using ROI and 0/14 without (p less than 0.001). The measurement of crest height changes in a region of previous severe vertical bone loss is demonstrated using serial films. The potential for using trabecular bone patterns as reference sites in regions where traditional measurement points are absent is demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430279 TI - Effects of ultrasonic and sonic scalers on dental plaque microflora in vitro and in vivo. AB - The effects of ultrasonic and sonic scalers on the subgingival microflora were investigated in vitro and in vivo. In the in vitro investigation, 27 plaque samples collected from periodontal pockets were submitted to ultrasonic and sonic vibrations for 10, 30 and 60 s. Bacterial suspensions were examined by darkfield microscopy to detect qualitative changes and cultured to evaluate the total number of cultivable bacteria. Microscopic counts following both instrumentations showed a decrease in the proportions of spirochetes and motile rods and an increase in the % of coccoids and rods. The changes were directly related to the time-period of instrumentation. Comparison between both types of instrumentation showed significant differences and more pronounced changes were observed with the ultrasonic than the sonic scaler. Spirochetes and motile rods were reduced to approximately 0.1% after ultrasonic treatment versus 24.7% after sonic instrumentation. Cultural observations showed a marked increase in total number of colony-forming units following both treatments. The clinical investigation included 66 periodontal pockets which were instrumented subgingivally for 10 and 30 s with ultrasonic or sonic scalers. Qualitative changes were similar to those observed in vitro, i.e., reduction in spirochete and motile rod counts as well as the other morphotypes with an increase in coccoid cells. Total counts of bacteria were reduced following debridement. No difference in the microscopic or cultural data was found between ultrasonic and sonic instrumentation. PMID- 1430280 TI - Cleaning effectiveness of chewing sticks among Tanzanian schoolchildren. AB - The oral hygiene of habitual chewing stick and toothbrush users who participated in an oral health education (OHE) programme in schools was evaluated. The study comprised all chewing stick users (n = 45) in standard 4 in 8 randomly selected experimental schools and all chewing stick users (n = 17) in standard 4 in 4 randomly selected control schools. Each chewing stick user was randomly matched with a toothbrush user of the same sex, age and school. Their ages ranged from 10 to 13 years with a mean of 11.5 years. The children in standard 4 of the 8 experimental schools received OHE. Among many topics aiming to improve oral health of children, the practice of systematic brushing was taught. The children practised weekly brushing sessions in schools under the supervision of instructed teachers. At baseline, the chewing stick users exhibited statistically significant more plaque, but their gingival condition was comparable with their matched toothbrush counter-parts. After 3 months, the chewing stick and the toothbrush users in the experimental schools, had reduced their plaque and gingival bleeding scores significantly to the same extent, whereas no substantial changes in oral hygiene occurred in the control group. The findings show that schoolchildren who participated in a school programme that emphasizes effective toothbrushing were able to improve their oral hygiene regardless of whether they were habitual chewing stick or toothbrush users. PMID- 1430281 TI - Associations between volume and flow rate of gingival crevicular fluid and clinical assessments of gingival inflammation in a population of British male adolescents. AB - Gingival crevicular fluid (GCF) sampling was performed on 2 occasions separated by 1 year, at 2 sites in the mouths of 102 male adolescents, mean age 17.85 years. Samples were collected onto 5 filter paper strips which were sequentially applied to the mouth of the crevice over a 9-min collection period. Volume and flow rates of GCF were determined for each site and were compared with clinical measurements of plaque, gingival colour, bleeding, gingival index (GI) and pocket depth, using a general linear models (GLM) procedure. While the initial volume of GCF showed no association with any clinical measurement, there was an association between flow rate of GCF and gingival colour. The volume of GCF collected in the final, 5th sample was associated with the GI. The sample site strongly influenced all measures of GCF volume. It is proposed that the flow rate of GCF may be a better indicator of gingival inflammation than the more imprecise clinical assessments of inflammation, since GCF flow rates more precisely reflect changes in tissue permeability. The association between the final sample, collected after 9 min, and clinical measurements, was probably a reflection of the association between clinically-detectable inflammation and the susceptibility of the site to mild irritation. PMID- 1430282 TI - Bleeding on probing as it relates to probing pressure and gingival health in patients with a reduced but healthy periodontium. A clinical study. AB - A previous study demonstrated that the bleeding on probing (BOP) test using uncontrolled forces may result in a proportion of false positive readings when used as a parameter for inflammation. A strong possibility exists for the traumatization of clinically healthy gingival tissues if a probing force exceeding 0.25 N is applied. While these results originated form young dental hygienists exhibiting excellent oral hygiene, the aim of the present study was to evaluate the relationship between probing pressures and gingival conditions in patients with a history of treated periodontal disease, i.e., in situations with a reduced but healthy periodontium. 10 patients who had been enrolled in a periodontal maintenance program following treatment of moderate to advanced chronic inflammatory periodontal disease consented to participate in the study. They were all selected on the basis of a record of excellent oral hygiene practices for at least 2-6 years and almost complete absence of clinical inflammation following successful periodontal therapy. Applying a probing force of 0.125, 0.25, 0.375 and 0.5 N in the 4 jaw quadrants, respectively, at 2 different occasions with an interval of 10 days, bleeding on probing was assessed. Oral hygiene and gingival conditions were determined using the criteria of the plaque and gingival index systems. All subjects showed significant increases in mean BOP% with increasing probing force applied (2.5%-7.9%). Regression analysis revealed an almost linear correlation and a significant correlation coefficient between BOP% and probing force. Almost identical slope inclinations were found when the 6 subjects with the lowest mean BOP% at 0.25 N were compared with the regression analysis of the total group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430283 TI - The use of irradiated-crosslinked human collagen membrane in guided tissue regeneration. AB - Irradiated glutaraldehyde-crosslinked human collagen membrane was evaluated for its effects on new attachment formation in clinical trials, using the principle of guided tissue regeneration (GTR). 19 adult periodontitis patients with 52 matched bilateral periodontal defects received scaling and polishing with oral hygiene instruction. The bilateral periodontal defects were treated by reflecting a flap with collagen membrane (test) or flap reflection alone (control). Plaque (P1I) and gingival index (GI) scorings, probing pocket depth (PPD) and probing attachment level (PAL) along with classification of furcation involvement (FI) and bony defects were made at pre- and post surgery (6 weeks, 3 and 6 months). Improvement of P1I and GI scores was seen in both test and control sites following the surgical therapy. Reductions in PPD and PAL were significantly (p less than 0.001) more pronounced at 6 months in the test sites compared to the controls. The 2 Class I furcations in the graft-treated teeth showed complete resolution, while the corresponding furcations in the control teeth showed incomplete closure. The use of human collagen membrane based on the GTR technique for treatment of human periodontal defects provided greater gain of clinical attachment than when flap surgery alone was undertaken. PMID- 1430284 TI - Buccal attachment loss in Swedish adolescents. AB - A case referent study was performed to identify factors connected with loss of buccal attachment in adolescents. The study group was identified among 18-year olds who had participated 2 years earlier in a study of periodontal conditions in adolescents. The criterion for inclusion in the case group was buccal attachment loss (greater than or equal to 1 mm) in one or more sites. Information on 28 variables, identified earlier as being related to recessions, was collected in a clinical examination, interview and observation. The referent group consisted of 66 subjects and the case group of 71 subjects. The case group comprised 2 subgroups, one identified as having buccal attachment loss in 1987 and the other with attachment loss occurring in the years 1987-89. Statistical analyses, using the chi 2 test, logistic regression and a variance component model, were performed to detect factors related to buccal attachment loss. These factors were thin alveolar tissue, narrow width of the attached gingiva and presence of teeth with buccal displacement. The results indicate that the anatomy of the buccal alveolar process is related to the presence of buccal attachment loss in populations with a high level of oral hygiene. To evaluate the importance of possible risk factors or etiological factors for development of buccal loss of tooth support, prospective epidemiological or experimental studies are needed. PMID- 1430285 TI - The relation between periodontitis and systemic bone mass in women between 46 and 55 years of age. AB - It has been suggested that periodontitis and systemic bone mass might be related. In order to evaluate this possible relationship, we performed an intra-oral examination and measured lumbar bone mineral density (lumbar BMD) and metacarpal cortical thickness (MCT) in 286 female volunteers between 46 and 55 years of age. In addition, the alveolar bone height was measured on bite wing radiographs of the dentate subjects. Of the subject, n = 60 (21%) were edentulous. Compared to the dentate subjects, the lumbar BMD and MCT of the edentulous women were not significantly different. In the dentate subjects, no significant correlation was observed between the clinical parameters of periodontitis (mean probing depth, occurrence of bleeding after probing and number of missing teeth) and the bone mass parameters (lumbar BMD and MCT); nor was a significant relation observed between the bone mass measurements and alveolar bone height. We therefore suggest that systemic bone mass is not an important factor in the pathogenesis of periodontitis. PMID- 1430286 TI - Gingivectomy versus flap surgery: the effect of the treatment of infrabony defects. A clinical and radiographic study. AB - The aim of this paper was to compare the short-term results of gingivectomy (GV) and modified Widman flap (MWF) surgery in the treatment of infrabony defects. 14 patients with 68 bilateral infrabony defects were selected. At baseline, and 3 and 6 months postoperatively, assessments of oral hygiene, gingival conditions, bleeding on probing, probing pocket depth and attachment level, were recorded. Conventional radiograps were obtained in a way that assured a reproducible projection geometry. In a split-mouth design, one jaw quadrant was randomly treated with GV, while the contralateral with a MWF. The changes of the bone tissue were assessed by means of conventional and subtraction images by 2 observers. The interobserver agreement of the conventional and subtraction technique was studied. The majority of the sites demonstrated a significant improvement in gingival conditions and a reduction in bleeding. For both treatments, probing depths were reduced by an average of 3 mm, while a mean of 1.22-1.35 mm of probing attachment gain was obtained. The GV resulted in slightly more gingival recession (1.90 mm) than the MWF (1.60 mm). The radiographic examination demonstrated gain of bone in 7 defects treated with GV and in 9 defects treated with MWF. This study demonstrated that pockets associated with infrabony defects can be successfully treated by both treatment modalities. Furthermore, bone gain can occur after treatment but not in a predictable manner. PMID- 1430287 TI - Periodontal diseases and HIV infection. A review of the literature. AB - There have been many references in the literature to HIV-related periodontal diseases, which although poorly substantiated, seem to have established them as part of the expected range of HIV-associated conditions. The original studies have produced conflicting reports which may stem from shortcomings in design. Consequently, the picture remains confused with respect to the classification, epidemiology, microbiology, natural history and management of HIV-related periodontal diseases. Future studies should give greater attention to sampling methods, the use of control groups and defining criteria. This will allow comparison of data between centres and facilitate study of what may be an uncommon disease. PMID- 1430288 TI - Remodelling of periodontal tissues adjacent to sites treated according to the principles of guided tissue regeneration (GTR). AB - The aim of the present study was to assess the remodelling of alveolar bone adjacent to periodontal sites following therapy according to the principles of guided tissue regeneration (GTR) using computer-assisted densitometric image analysis (CADIA), and to compare the radiographic results to traditional clinical parameters. As required for digital subtraction analyses, periodically reproducible radiographs were obtained using a modification of the Rinn System and individual acrylic bite blocks for periodical identical radiographs. Ideally, a digital subtraction image from a site where absolutely no change in density had occurred would show a perfect cancellation of the structures. An average grey level value of 128 (the middle of the digitizer grey level range set by software) would show up at each pixel. Areas with grey levels < 128 in the subtraction image would indicate loss in density and grey levels > 128 would indicate increase in density. Within the subtraction images, areas were defined using the cursor to draw "regions of interest" (ROI) projected on the bony defect exposed to GTR covering the crestal bone as well as the region of potential "bonefill". The mean, median, the standard deviation and range of the grey levels of pixels within a particular ROI were calculated. Similarly sized ROI were drawn in bone areas not exposed to the GTR procedure serving as controls. The differences in the mean grey levels of all pixels within a particular ROI between the baseline, 3 and 12 months images were calculated for documentation of gain or loss in density. From 14 patients, standardized radiographs were available from baseline, 3 months and 12 months postsurgically, depicting one infraosseous defect before and after treatment according to the principles of GTR. The densitometric changes observed in these defects were compared to the clinically assessed changes measured at the site with the deepest baseline pocket depth. A mean clinical attachment gain of 2.36 mm after 3 and 3.22 mm after 12 months was measured. This was associated with a mean reduction in the PPD amounting to 3.36 mm and 3.79 mm, respectively. The changes in the level of the FGM were rather small considering the deep original mean PPD of 7.07 mm. Over the first months, a mean recession of 1.14 mm was observed which was followed by a coronal displacement of 0.43 mm. With respect to the remodelling of the alveolar bone adjacent to the defects assessed by means of CADIA, the most pronounced changes occurred when comparing the baseline to the 12 months radiographs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1430289 TI - Validity issues in split-mouth trials. AB - The main purpose of the split-mouth design is to remove all components related to differences between subjects from the treatment comparisons. By making within patient comparisons, rather than between-patient comparisons, the error variance (noise) of the experiment can be reduced, thereby obtaining a more powerful statistical test. Unfortunately, comparisons made on a within-patient basis have potential disadvantages. Treatments may have effects on experimental units other than those which they were assigned to (carry-across effects). Such effects cannot be estimated from split-mouth data. Neither can treatment effects be estimated. The estimable parameter in a split-mouth design is the treatment effect plus the sum of all carry-across effects. Unless a priori knowledge indicates that no carry-across effects exist, reported estimates of treatment efficacy are potentially biased. In the design of split-mouth clinical trials, potential gain in precision should be carefully weighed against a potential decrease in validity. PMID- 1430290 TI - Periodontal status in insulin-dependent diabetic adolescents. AB - A cross-sectional study was designed to evaluate the periodontal status of 85 12 18 year-old French adolescents with insulin-dependent diabetes (IDDM) and 38 healthy controls in the same age group. The clinical examination consisted of plaque control and gingival inflammation evaluation and probing attachment level. The interproximal marginal bone level was assessed with bitewing radiographs taken on the first molars and on areas presenting an attachment loss over 2 mm. Diabetic children had significantly more gingival inflammation than children without diabetes, in spite of similar plaque scores. No significant relation between gingival condition and age, Tanner's index, HbAlc level or disease duration could be demonstrated. None of the subjects had sites with attachment loss > or = 3 mm or radiographic signs of periodontitis. PMID- 1430291 TI - Guided tissue regeneration using biodegradable membranes of polylactic acid or polyurethane. AB - The purpose of the present investigation was to evaluate the use of biodegradable membranes of polylactic acid or polyurethane for obtaining regeneration following treatment of circumferential periodontal defects in monkeys with the "guided tissue regeneration" procedure. Orthodontic elastic bands were placed around selected test and control teeth in 4 monkeys in order to induce breakdown of the periodontal tissues. When the destruction of the supporting tissues had progressed to a level corresponding to approximately half the length of the roots, the elastic bands were removed. After 1 to 8 months, full thickness flaps were raised on the buccal and lingual aspects of both test and control teeth. The exposed root surfaces were scaled and a notch was prepared in the root surface at the level of the reduced bone crest. Membranes of polylactic acid or polyurethane were placed circumferentially around the test teeth, while no membranes were placed around the control teeth. The tissue flaps were then sutured in a coronally displaced position. The surgical procedures and sacrifice of the animals were scheduled to provide observation times of 1, 4 and 8 months. During the healing period, various complications such as recession of the flap margins and exposure or exfoliation of the membranes were noticed. The histological analysis showed that the amount of new connective tissue attachment on test and control teeth did not differ and was restricted to the most apical part of the lesions. The bio-degradable membranes could be identified in a few specimens, and they were always surrounded by an epithelial layer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430292 TI - Histological evaluation of surgically treated oral tissues after application of a photocuring periodontal dressing material. An animal study. AB - At present no information is available about biological effects on oral tissues of the photocuring periodontal dressing Barricaid. This animal study examines histologically the tissue responses of surgical areas covered during 7 days with either Barricaid, the eugenol-containing dressing Ward's Wondrpak or the bionert control gel Carboxyl Methyl Cellulose. One group was studied immediately after the removal of the dressings; in the other group, further healing was permitted for another week. Results after 7 days indicate acute inflammatory reactions in the test areas without significant differences between the 2 periodontal dressing materials. The control areas showed to a lesser degree basically the same tissue response. In the 2nd week, generally all areas healed. After 14 days, no differences between test- and control sites could be detected. From a biological point of view, these findings suggest no contra-indication for application of this photocuring dressing material after periodontal surgery. PMID- 1430293 TI - Endodontic infection and calcium hydroxide-treatment. Effects on periodontal healing in mature and immature replanted monkey teeth. AB - Large experimental defects with marginal communication, and small isolated experimental defects were created on the root surfaces of extracted monkey lateral incisors with either open or closed apices. The pulp tissue was either infected or removed, and calcium hydroxide placed in the root canal. The teeth were then replanted and the healing pattern evaluated histomorphometrically after 20 weeks. From the results, it was concluded that (1) an intrapulpal infection promotes marginal epithelial down-growth on a denuded dentin surface irrespective of tooth developmental stage, and that (2) the periodontal healing potential after calcium hydroxide-treatment appears to be higher in teeth with open apices compared with teeth with closed apices, where ankylosis was promoted as opposed to teeth with open apices where significantly more reparative cementum was found. PMID- 1430294 TI - Progression of periodontal disease in patients with mild to moderate adult periodontitis. AB - The aim of the present study was to determine the progression rate of periodontal disease in patients treated for localized or generalized mild to moderate adult periodontitis. 52 patients with a mean age of 53.7 years (S.D. 12.6 years) were instructed in optimal home care procedures and exposed to initial periodontal therapy, before reconstructive therapy was initiated. Following completion of the prosthetic procedures, supportive therapy was offered to a limited extent and maintenance visits were irregularly scheduled corresponding to traditional dental care. Clinical periodontal parameters from 4 sites per tooth were assessed at the initial examination, at the time of reevaluation after initial therapy and at the re-examination after 8-years. Full sets of intraoral radiographs from the initial and the 8-year re-examination were analyzed with respect to changes in the radiographic alveolar bone height as a % of the total tooth length. As the result of the home care instructions, the mean plaque index (plaque control record) amounted to 21% at the end of initial periodontal therapy. 8 years later, the re examination revealed a mean plaque index of 49% and a mean gingival bleeding index of 24%. At the initial examination, the 52 patients presented with an average of 18.7 teeth. During treatment, 26 teeth were sacrificed and 19 teeth were lost over the 8 years of supportive therapy. Bicuspids were the most frequent teeth to be lost over the observation period. As a result of initial therapy, the mean pocket probing depths decreased significantly. However, after 8 years, only minor differences were found when compared to the initial examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430295 TI - Marginal bone level in the normal primary dentition. AB - The aim of the present study was to establish the normal range for the radiographic distance between the cemento-enamel junction (CEJ) and the marginal bone level (MBL) in the primary dentition, and to relate this distance to various physiological and pathological factors. 128 children at the ages 7, 8 and 9 years took part in the study. Clinical and radiographic examinations of the mesial and distal surfaces of all primary molars and the distal surface of the primary canines were performed. The clinical examination included measurements of the amounts of plaque, bleeding on probing, probing depth and probing attachment loss. In addition, increased mobility of the primary teeth and stage of eruption of the neighbouring permanent teeth were recorded. The radiographic examination included measurements of the CEJ-MBL distance and the remaining root length. Also, exfoliating teeth, presence of proximal dentin caries, restorations and calculus were recorded from the radiographs. Associations between various explanatory variables and the CEJ-MBL distance were tested with both a chi 2 test and a variance components analysis. The mean CEJ-MBL distance for all primary tooth surfaces was 1.0 mm. Individual surfaces displayed distances ranging from 0.0-4.0 mm. Of the variables tested for association with the CEJ-MBL distance, eruption of neighbouring permanent tooth and exfoliation of neighbouring primary tooth seemed to be associated with large CEJ-MBL distances. When surfaces with these characteristics were excluded, a CEJ-MBL range of 0.0-2.0 mm was obtained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430296 TI - The effect of using a pre-brushing mouthwash (Plax) on oral hygiene in man. AB - The aim of this study was to investigate whether the use of a pre-brushing mouthwash (Plax) improved subjects' oral hygiene over a 2-week period. In a double-blind placebo controlled cross-over study, 33 adult subjects (mean age 35.3 years) used either Plax or a placebo mouthwash for 30 s prior to toothbrushing during a 2-week period. After a washout period of 4 weeks, the subjects used the other mouthwash in the same way. The modified plaque index of Quigley and Hein (QHI) was recorded for 16 teeth (16, 14, 13, 11, 21, 23, 24, 26, 36, 34, 33, 31, 41, 43, 44, 46) at each visit. The bleeding index (BI) was recorded at the beginning and end of the study. Results were analysed using a paired one-tailed t-test. Neither plax nor placebo mouthwashes reduced plaque scores significantly (p > 0.05) below baseline. There was no statistically significant difference between the mean BI at the beginning of the trial (0.42) and at the end (0.44). These results suggest that the routine use of Plax is not a useful adjunct to toothbrushing. PMID- 1430297 TI - Clinical pharmacology: medicine or pharmacology. PMID- 1430298 TI - Workshop on problem-based learning as a method for teaching clinical pharmacology and therapeutics in medical school. PMID- 1430299 TI - Oral absolute bioavailability and intravenous dose-proportionality of cefprozil in humans. AB - The absolute bioavailability (F) and dose proportionality of cefprozil were investigated in a parallel design study with an embedded two-way crossover leg. Twenty-four healthy male subjects divided into 3 dosing groups received a single 250-, 500-, or 1000-mg dose of cefprozil by a 30-minute intravenous infusion. Subjects assigned to the 500-mg dose group also received a 500-mg oral dose of cefprozil in crossover manner with a wash-out period of 7 days between each treatment. Cefprozil consists of cis and trans isomers in an approximate 90:10 ratio. Serial blood and urine samples were collected and analyzed for the concentrations of the cis and trans isomers of the cephalosporin using high pressure liquid chromatographic assay with UV detection methods. After the 250-, 500-, and 1000-mg intravenous administration of cefprozil, the peak concentrations were 13.2, 26.0, and 48.5 micrograms/mL, and area under the plasma concentration versus time profiles were 17.2, 31.4, and 58.1 micrograms.hour/mL, respectively, for the cis isomer increasing in a dose proportional manner. Total body clearance, renal clearance, and volume of distribution at steady state, adjusted for body weight, were not significantly different among all groups. Mean residence time, elimination half-life, and urinary recovery were invariant with the dose. Based on the plasma and urine data, the estimates of F were 89% and 94% for the cis isomer, respectively. The plasma concentrations of the trans isomer were about 1/10th of the cis isomer, and all parameters were similar to those observed for the cis isomer. In summary, cefprozil exhibits linear pharmacokinetics and is essentially completely absorbed after oral administration. PMID- 1430300 TI - Sustained antihypertensive activity of diltiazem SR: double-blind, placebo controlled study with 24-hour ambulatory blood pressure monitoring. AB - A new polymeric matrix technology provides a sustained-release formulation of diltiazem hydrochloride (diltiazem SR) suitable for once-daily therapy. The efficacy and safety of diltiazem SR were evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a single-blind, placebo lead-in period, 275 patients with mild to moderate essential hypertension were assigned to receive placebo or diltiazem SR 120, 240, 360, or 480 mg once daily for 4 weeks. The efficacy evaluation was based on office and 24-hour ambulatory blood pressure monitoring. Twenty-four hours after the last dose in the 4-week, double-blind treatment period, the mean reduction from baseline in supine diastolic blood pressure ranged from 5.1 to 10.6 mm Hg in the diltiazem SR 120- to 480-mg groups, resulting in a significant linear trend across all treatments (P less than .001). Reductions in systolic blood pressure were similar. Ambulatory blood pressure monitoring, performed in 138 patients, confirmed the dose-response relationship and showed consistent antihypertensive activity throughout the 24-hour dosing interval. The percentage of patients reporting adverse events was similar in the placebo- and active-treated groups. The results of this study indicate that diltiazem SR is well tolerated, lowers blood pressure in a dose-related manner, and provides sustained activity throughout the 24-hour dosing interval. PMID- 1430301 TI - Circadian changes of valproate kinetics depending on meal condition in humans. AB - The objective of this study was to examine the effect of meal condition on circadian changes in valproic acid (VPA) kinetics. Two experiments were performed in 16 healthy men that were synchronized with diurnal activity and nocturnal rest as their routine life. In both experiments, four 200-mg tablets of VPA were given orally on two occasions in the morning (8:30 AM) or in the evening (8:30 PM). In each study, a randomized, single-dose, two-way crossover design was used, and 2 weeks elapsed between morning and evening trials. In experiment 1, eight subjects took a light meal as breakfast between 8:00 and 8:15 AM and a heavy meal as dinner between 6:00 and 6:30 PM to fit the subject's usual food amount. The mean peak plasma concentration (Cmax) was significantly higher (P less than .01), the time to peak concentration (tmax) was shorter (P less than .05), and the absorption rate (Ka) was larger (P less than .05) after the morning dose than after the evening dose. In experiment 2, the size and contents of meal in breakfast and dinner were prepared in the same manner as the standard breakfast for the subjects. Namely, eight subjects took the same light meal between 8:00 and 8:15 AM in the morning and between 8:00 and 8:15 PM in the evening. There was no significant circadian change in VPA kinetics under this same meal condition. These results suggest that the differences of meal condition between morning and evening in our daily life play a major role in the mechanism underlying the circadian changes of VPA absorption in man. PMID- 1430302 TI - Impact of food on the bioavailability of encainide. AB - The bioavailability of drugs that undergo extensive presystemic hepatic metabolism may be increased by concomitant ingestion with food. The effect of food on the bioavailability of encainide, a class IC antiarrhythmic agent, was evaluated in 14 healthy subjects in this randomized crossover study. The subjects received encainide 35 mg every 8 hours for 7 days and were randomized to receive their test dose of encainide with food or after an overnight fast. Encainide area under-the-concentration versus time curve (AUCs) were detectable in 3 of 14 subjects after fasting and in 7 of 14 after feeding. Although food increased the mean encainide AUC by more than threefold, this increase did not reach statistical significance because of the large number of subjects with indeterminate encainide AUCs. Food did significantly increase the AUC of O demethyl-encainide (ODE), but not the AUC of methoxy-O-demethyl-encainide (MODE). Despite the increase in ODE AUC, no significant effect on the surface electrocardiogram 2 hours after dose administration could be detected. Food may increase the bioavailability of encainide and one of its active metabolites (ODE). The clinical relevance of this pharmacodynamic effect warrants further evaluation. PMID- 1430303 TI - Chronopharmacology of furosemide in the elderly. AB - The authors have previously reported the time-dependent change in the diuretic effects of furosemide, a loop diuretic agent, in young and middle-aged subjects. The current study was undertaken to examine an influence of aging on this chronopharmacologic phenomenon. Ten milligrams furosemide was given intravenously to 12 elderly subjects (greater than 70 years of age) at 9:00 AM (day trial) or at 9:00 PM (night trial) by a cross-over design. One-hour urine samples were collected for 3 hours after each administration, and urine volume and urinary excretions of sodium and furosemide were determined. Urine volume and urinary sodium excretion increased after furosemide administration. Contrary to the findings in the young and middle-aged subjects, no significant differences were observed in these parameters at any observation period between the day and night trials in the elderly subjects. Urinary furosemide excretion of the day and night trials did not significantly differ. These results suggest that the chronopharmacologic profiles of furosemide are altered in the elderly. PMID- 1430304 TI - Advances in Cardiovascular Pharmacology: Protocol Design and Methodology. Proceedings of the 11th annual symposium. Atherosclerosis and Drug Development for Ischemic Heart Disease. PMID- 1430305 TI - A new specific antibody reveals octopamine-like immunoreactivity in cockroach ventral nerve cord. AB - An antiserum was raised in rabbits immunized with octopamine conjugated to thyroglobulin. The specificity of this antiserum for octopamine is shown by dot blot immunoassay analysis. The antiserum does not crossreact with dopamine, noradrenaline, and serotonin, but slight crossreactivity with the amine tyramine at high concentrations was observed. The tyramine crossreactivity could be eliminated by preabsorption with a tyramine-glutaraldehyde-BSA conjugate. Using this antiserum, we describe the topographical distribution of octopamine immunoreactive (ir) neuronal elements in wholemounts and paraffin sections of the ventral nerve cord of the American cockroach. The pattern of octopamine immunostaining is completely different from that obtained with an antidopamine serum, and can be blocked by preabsorbing the antioctopamine serum with BSA conjugated octopamine. Cell bodies and dendritic processes of putatively octopaminergic dorsal (DUM) and ventral (VUM) unpaired median neurons were clearly octopamine-ir in all ganglia examined. The numbers of stained DUM somata in the mesothoracic, metathoracic, and terminal ganglion of females correspond to those of peripherally projecting DUM cells revealed previously by retrograde tracing (Gregory, Philos Trans R Soc Lond [Biol] 306:191, 1984; Tanaka and Washio, Comp Biochem Physiol 91A:37, 1988; Stoya et al., Zool Jb Physiol 93:75, 1989). In addition, various, previously unknown, paired cells with octopamine like immunoreactivity were found in all ventral ganglia except abdominal ganglia 3-6. Some of these probably project intersegmentally. PMID- 1430306 TI - Functional degeneration of isolated central stumps of crayfish sensory axons. AB - In the crayfish, Procambarus clarkii, nerve 5 carries primarily sensory axons from the tail fan to the 6th abdominal ganglion where they synaptically activate interneuron A. Since the sensory neurons have their somata located at the periphery, transection of nerve 5 part way to the ganglion allowed us to examine the fate of their soma-less central stumps. Up to 3 weeks postlesion the response to stimulation of nerve 5 consisted of a brief latency spike in interneuron A, similar to that in control animals and to stimulation of the intact nerve 4. Stimulation of the lesioned nerve 5 beyond 3 weeks failed to fire interneuron A. This loss of function was correlated to loss of axons in nerve 5 deduced by comparing the numbers in the lesioned nerve 5 to its contralateral intact counterpart. The numbers are about equal in the paired nerves but rapidly decline on the lesioned side to 50% within 1 week, 20% within 3 weeks, and less than 10% in subsequent weeks. This loss affects all size classes of axons. However, in the 3 week lesioned nerve large glial infoldings subdivided some of the larger axons and single nuclei were seen in a few of the medium-sized axons. Possibly subdivision of large axons by glial infolding may introduce glial nuclei into axons. PMID- 1430307 TI - Distribution of the mRNA for a metabotropic glutamate receptor (mGluR1) in the central nervous system: an in situ hybridization study in adult and developing rat. AB - Distribution of the mRNA for a metabotropic glutamate receptor (mGluR1), which is linked to phosphoinositide (PI) hydrolysis, was investigated in adult and developing rat central nervous system (CNS) by in situ hybridization. Transcripts of mGluR1 were specifically localized to neurons and widely distributed throughout the adult rat brain. Most intensely labeled neurons were Purkinje cells of the cerebellum, mitral and tufted cells of the olfactory bulb, and neurons in the hippocampus, lateral septum, thalamus, globus pallidus, entopeduncular nucleus, ventral pallidum, magnocellular preoptic nucleus, substantia nigra, and dorsal cochlear nucleus. Moderately labeled neurons were seen in high density in the dentate gyrus, striatum, islands of Calleja, superficial layers of the retrosplenial, cingulate and entorhinal cortices, mammillary nuclei, red nucleus, and superior colliculus. In the developing rat brain, the level of mGluR1 expression gradually increased during early postnatal days in accordance with the maturation of neuronal elements. These results show prominent expression of mGluR1 in the major targets of putative glutamatergic pathways and unique distribution pattern of mGluR1 distinct from those reported for ionotropic subtypes of glutamate receptors, suggesting specific roles of mGluR1 in the glutamatergic system. PMID- 1430308 TI - Projections of leg proprioceptors within the CNS of the fly Phormia in relation to the generalized insect ganglion. AB - We previously reported a modality-specific layering of leg sensory axons in the CNS of the flies Phormia regina and Drosophila melanogaster with tactile and gustatory axons projecting into a ventral layer and the proprioceptive hair plate axons into an intermediate layer. Here the description is expanded to include the afferent projections of campaniform sensilla on the legs and wings of Phormia. The leg campaniform sensilla produce a number of patterns of projections within an intermediate layer of their ganglion, some of which project intersegmentally into the other thoracic ganglia. One of these patterns is shared by the hair plate sense organs. Selected wing campaniform sensilla were also stained and showed that there is little or no overlap between the projections of leg and wing campaniform sensilla. Similarities with the arrangement of campaniform sensilla and their central processes in Drosophila melanogaster are discussed. To apply the results of this study to a broader range of insects we provide an atlas of the fly CNS and compare it with the locust, which has been the model for much insect neuroanatomy and neurophysiology. PMID- 1430309 TI - Distribution of protein gene product 9.5 (PGP 9.5) in the vertebrate retina: evidence that immunoreactivity is restricted to mammalian horizontal and ganglion cells. AB - Using light microscopic immunocytochemistry, we have studied the distribution of protein gene product 9.5 (PGP 9.5), a neuron-specific protein first extracted from human brain (Doran et al., '83:J. Neurochem. 40:1542-1547), in the vertebrate retina. Retinas were obtained from frog, chicken, rat, rabbit, cow, cat, dog, and human. No immunoreactivity was observed in frog and only a faint staining was present in chicken. In mammalian retinas, a strong positive reaction was restricted to horizontal and ganglion cells, with minor interspecies variations. Immunostaining was present throughout the cell body and the dendritic tree in horizontal cells. At the level of retinal ganglion cells, immunolabel was particularly abundant in cell bodies and axons forming the optic nerve. Only the main dendrites were stained, the remainder of the dendritic tree giving rise to a diffuse punctate reaction in the inner plexiform layer. In rats, displaced amacrine cells, which are known to contribute largely (40-50%) to the total neuronal population within the ganglion cell layer (Perry, '81: Neuroscience 6:931-944) were not immunoreactive, as demonstrated from (i) analysis of the morphology, cell size and cell density of immunoreactive neurons in wholemounts; (ii) colocalization of retrograde label and PGP 9.5 immunoreactivity in about 80% of ganglion cells after injection of peroxidase into the optic nerve; and (iii) reduction of immunoreactivity in the inner plexiform and ganglion cell layers following optic nerve transection. Western blot analysis of extracts from rabbit retinas indicated that the immunoreactive species is PGP 9.5 or a closely related molecule. Recent studies have demonstrated that PGP 9.5 is a ubiquitin carboxyl terminal hydrolase (Wilkinson et al., '89:Science 246:670-673). The present results, therefore, suggest that differences in the ubiquitination process exist between retinal neurons. PMID- 1430310 TI - Neurons in the cockroach nervous system reacting with antisera to the neuropeptide leucokinin I. AB - Antisera were raised against the myotropic neuropeptide leucokinin I, originally isolated from head extracts of the cockroach Leucophaea maderae. Processes of leucokinin I immunoreactive (LKIR) neurons were distributed throughout the nervous system, but immunoreactive cell bodies were not found in all neuromeres. In the brain, about 160 LKIR cell bodies were distributed in the protocerebrum and optic lobes (no LKIR cell bodies were found in the deuto- and tritocerebrum). In the ventral ganglia, LKIR cell bodies were seen distributed as follows: eight (weakly immunoreactive) in the subesophageal ganglion; about six larger and bilateral clusters of 5 smaller in each of the three thoracic ganglia, and in each of the abdominal ganglia, two pairs of strongly immunoreactive cell bodies were resolved. Many of the LKIR neurons could be described in detail. In the optic lobes, immunoreactive neurons innervate the medulla and accessory medulla. In the brain, three pairs of bilateral LKIR neurons supply branches to distinct sets of nonglomerular neuropil, and two pairs of descending neurons connect the posterior protocerebrum to the antennal lobes and all the ventral ganglia. Other brain neurons innervate the central body, tritocerebrum, and nonglomerular neuropil in protocerebrum. LKIR neurons of the median and lateral neurosecretory cell groups send axons to the corpora cardiaca, frontal ganglion, and tritocerebrum. In the muscle layer of the foregut (crop), bi- and multipolar LKIR neurons with axons running to the retrocerebral complex were resolved. The LKIR neurons in the abdominal ganglia form efferent axons supplying the lateral cardiac nerves, spiracles, and the segmental perivisceral organs. The distribution of immunoreactivity indicates roles for leucokinins as neuromodulators or neurotransmitters in central interneurons arborizing in different portions of the brain, visual system, and ventral ganglia. Also, a function in circuits regulating feeding can be presumed. Furthermore, a role in regulation of heart and possibly respiration can be suggested, and probably leucokinins are released from corpora cardiaca as neurohormones. Leucokinins were isolated by their myotropic action on the Leucophaea hindgut, but no innervation of this portion of the gut could be demonstrated. The distribution of leucokinin immunoreactivity was compared to immunolabeling with antisera against vertebrate tachykinins and lysine vasopressin. PMID- 1430311 TI - Localization of 3H-nicotine, 125I-kappa-bungarotoxin, and 125I-alpha-bungarotoxin binding to nicotinic sites in the chicken forebrain and midbrain. AB - We have previously localized cholinergic cell bodies and fibers within the midbrain of the chicken with choline acetyltransferase immunohistochemistry. In a continuing effort to characterize the central cholinergic system, the present study examines the distribution of various nicotinic acetylcholine receptors in the forebrain and midbrain of the chicken. The binding of 3H-nicotine, 125I-kappa bungarotoxin, and 125I-alpha-bungarotoxin was localized by film autoradiography in adjacent sections of the adult chicken brain, allowing a comparison of the distribution of different classes of nicotinic binding sites within the brain. Although all three ligands were often co-localized, there were areas that bound 3H-nicotine but not the 125I-neurotoxins, or vice versa. Very high densities of all three ligands were found in the hyperstriatum ventrale; the nucleus geniculatus lateralis, pars ventralis; the griseum tectale; the nucleus dorsolateralis anterior thalami; the nucleus lentiformis mesencephali, pars lateralis and pars medialis; the periventricular organ; and the stratum griseum et fibrosum superficiale, layer f of the optic tectum. The nucleus spiriformis lateralis had the highest levels of 3H-nicotine binding in the chicken brain, but it did not bind either of the two snake neurotoxins. On the other hand, high levels of both 125I-alpha-bungarotoxin and 125I-kappa-bungarotoxin binding were found in the nucleus semilunaris and the nucleus ovoidalis, but these areas contained little or no 3H-nicotine binding. No unique 125I-kappa-bungarotoxin sites, unrecognized by 125I-alpha-bungarotoxin, were identified by the low resolution autoradiography performed in this study. In general, nicotinic receptors were found in areas that have been reported to contain cholinergic cell bodies or fibers. Comparison of our results with the expression of neuronal nicotinic receptor subunits, as determined by in situ hybridization, suggests that many of the high affinity 3H-nicotine sites are localized presynaptically, as, for example, in the retinorecipient nuclei and the nucleus interpeduncularis. The lack of 125I-kappa-bungarotoxin binding in the presence of alpha-bungarotoxin indicates that the chicken brain has only very low levels of a unique kappa bungarotoxin site. This is in marked contrast to chicken, frog, and rat autonomic ganglia, where a unique kappa-neurotoxin-sensitive receptor has been identified and shown to mediate nicotinic neurotransmission. PMID- 1430312 TI - Novel developmental boundary in the cerebellum revealed by zebrin expression in the lurcher (Lc/+) mutant mouse. AB - The cerebellar cortex contains at least two classes of Purkinje cells, which are organized into alternating arrays of parasagittal bands. The clearest demonstration of this compartmentation is the pattern of expression of a family of polypeptide antigens, the zebrins, which are expressed selectively by Purkinje cell subsets. Furthermore, anterograde tracing experiments show that the zebrin compartments are closely correlated with both afferent and efferent projection maps. The further subdivision of long parasagittal bands into smaller modules may occur through several different mechanisms, including the intrinsic cerebellar lobulation and the selective distribution of afferent terminal fields. However, while the longitudinal subdivisions are straightforwardly shown, the mediolateral boundaries are more subtle. In this report we describe a novel mediolateral and anteroposterior compartmentation boundary in mice, running across lobule VIII, that is revealed by the consequences of the lurcher (Lc/+) allele for zebrin expression. In normal mice zebrin compartmentation develops in several discrete stages: until postnatal day 5 (PD5) there is no zebrin expression; from PD5-PD7 zebrin is found only in the posterior lobe vermis, with immunoreactive Purkinje cells in lobules X, IX, and VIII but not elsewhere; from PD7-PD12 most Purkinje cells in the vermis become zebrin+; from PD12-PD15 immunoreactivity also appears in the hemispheres so that almost all Purkinje cells now are zebrin+; and finally, from PD15-PD25 zebrin is gradually suppressed in those Purkinje cells that are zebrin- in the adult until the mature pattern of parasagittal compartments is revealed. In the Lc/+ mutant the normal developmental progression is interrupted at around PD7. As a result, the pattern of zebrin expression becomes frozen at that stage when immunoreactive Purkinje cells are confined exclusively to the posterior lobe vermis. A reproducible boundary between expressing and nonexpressing zones runs mediolaterally across the dorsal surface of lobule VIII. Apart from zebrin expression itself, there are no obvious structural correlates of this transition. This mediolateral boundary identifies a developmental unit in the posterior lobe vermis of the cerebellum, and provides further evidence that the cerebellum is a highly heterogeneous structure. PMID- 1430313 TI - Survival and integration of bovine chromaffin cells transplanted into rat central nervous system without exogenous trophic factors. AB - Our previous studies have demonstrated that suspension grafts of isolated bovine chromaffin cells survive in the periaqueductal gray (PAG) of rat midbrain for up to 1 year after transplantation. The current study aimed to determine whether this type of graft could survive transplantation into sites other than the PAG that can benefit from chromaffin cell secretory products. In this study, electron microscope analysis showed that chromaffin cells implanted into the frontal neocortex, striatum, PAG, or the subarachnoid space overlying the spinal cord survived for at least 8 weeks without evidence of degeneration. Intraparenchymally placed grafts appeared relatively avascular and well integrated within the host parenchyma. When blood vessels were found, they were primarily at the host-graft border and were of the nonfenestrated central nervous system (CNS) type. Numerous synapses were present between the grafted cells and host neuronal processes. In addition, extensive intercommunication, via gap junction-like structures, was common in the grafts. Morphologic evidence of granular secretion was most commonly seen in striatal grafts. In contrast, subarachnoid grafts displayed minimal interaction with the host spinal tissue and were heavily vascularized with fenestrated capillaries. Despite morphologic differences between intra- and extraparenchymal grafts, this study demonstrates that isolated suspensions of bovine chromaffin cells survive transplantation into CNS sites without exogenous trophic factors and suggests that these cells are potential candidates for neural transplantation into these regions. PMID- 1430314 TI - Rapid rearrangement of intrinsic tangential connections in the striate cortex of normal and dark-reared kittens: lack of exuberance beyond the second postnatal week. AB - Clustered intrinsic connections in the kitten striate cortex originate from an unclustered, diffusely organized pattern prevailing during the first postnatal week. We have studied the progress of this reorganization and its dependence on visual input by determining the topographies of the intrinsic tangential connections at various postnatal ages by means of axonal tracing methods. Neurons were labeled either by diffusion of the carbocyanin dye DiI in animals ranging in age between 1 day and 30 days, or by retrograde transport of fluorescent microspheres in animals ranging in age between 7 days and 11 months. Quantitative evaluation of retrogradely labeled neurons revealed that during the first postnatal week, intrinsic tangential connections are organized in an unclustered fashion. During the second postnatal week a rapid rearrangement of connections occurs and is complete around postnatal day 11. The main events taking place during the course of this rearrangement are a decrease in the density of tangential connections and an arrangement of them in a clustered fashion. Once the clusters have been formed, the periodicity of the clustered pattern of connections and the size and distinctness of the clusters do not change. This means that the system of clustered tangential connections is adult-like at the end of the second postnatal week. Dark rearing affects neither the rapid rearrangement of horizontal connections into an adult-like system of clusters, nor the integrity of this clustered topography until the end of the first postnatal month. The overall distribution and the lateral extent of the tangential connections remain about the same during the postnatal period and are not affected by dark rearing until the end of the first postnatal month. We conclude that the clustered system of tangential connections in the cat's striate cortex is determined innately. PMID- 1430315 TI - Muller cells in vascular and avascular retinae: a survey of seven mammals. AB - Eight monoclonal antibodies were used to label Muller cells in four mammals that have vascular retinae (cats, dogs, humans, and rats) and in three with avascular retinae (echidnas, guinea pigs, and rabbits). Muller cells were found to have a fairly uniform retinal distribution in seven species, with a mean density of 8,000-13,000 cells mm-2. Muller cells in avascular retinae differ from their vascular counterparts in four respects. First, they are shorter than those in vascular retinae. This difference is mainly due to a reduction in the thickness of the outer nuclear layer. Second, the trunks of Muller cells in avascular retinae tend to be thicker, although those in echidnas are an exception to this trend. Third, Muller cell rootlets in avascular retinae follow a more tortuous course than those in vascular retinae, reflecting the fact that photoreceptor nuclei in the two types of retina have different shapes and stacking patterns. Fourth, due to a reduction in the density of photoreceptors in avascular retinae, there are fewer neurones per Muller cell. Although these four features may enable Muller cells to assist the nutrition of neurones in the inner layers of avascular retinae, they are unlikely to be morphological specializations that have evolved for that purpose. Rather, these features appear to be a direct consequence of the fact that avascular retinae are thinner and have a differently organised outer nuclear layer. These features aside, Muller cells in avascular retinae closely resemble their counterparts in vascular retinae. PMID- 1430316 TI - Prenatal formation of the normal mouse corpus callosum: a quantitative study with carbocyanine dyes. AB - Judgment of abnormalities in fetal cortical axon development is more sensitive when a good standard of normal ontogeny is established. The recent availability of postmortem tract tracing methods has greatly improved the observation of axon extension and growth cone morphology in mouse fetuses, which allows much stronger statements about the timing of crucial steps in the formation of the corpus callosum in particular. The first outgrowth and crossing of midplane by axons of the corpus callosum (CC) were examined in 153 normal mouse embryos and fetuses of the hybrid cross B6D2F2/J with carbocyanine dyes applied to brains fixed by perfusion. In most brains a crystal of DiI was inserted into either frontal, parietal, temporal, or occipital cortex in one hemisphere, and a crystal of DiA was placed into a different site in the opposite hemisphere. Although dye diffusion obscured the emergence of axons, linear regression analysis revealed that the first callosal axons emerged from their cortical cells of origin at about 0.4 g body weight or 15.5 days after conception for all four sites. Subsequent axon growth rate was substantially faster for those from frontal cortex (3.2 mm/day) than occipital cortex (1.8 mm/day). Axons from frontal cortex crossed the cerebral midplane first (0.69 g, E16.3), followed by those from parietal (0.74 g), temporal (0.77 g) and occipital cortex (0.92 g, E16.9). Prior to crossing midplane, the pioneering CC axons were usually 200 microns or less in advance of the main bundle, but when they crossed midplane and encountered CC axons growing from homotopic sites in the opposite hemisphere, the pioneering axons were often 0.5 to 2.5 mm ahead of the main bundle. Growth cones were usually large and complex until they had crossed midplane and were thereafter smaller with simple and flat morphologies. The topography of axons in the CC at midplane was organized according to cortical region of origin from the very beginning, when the CC was only a small cap over the hippocampal commissure and dorsal septum. The quantitative results provide a convenient standard for normal callosal development in mice and should facilitate comparative studies. PMID- 1430317 TI - Distribution of corticotropin-releasing factor-like immunoreactivity in squirrel monkey (Saimiri sciureus) amygdala. AB - Previous anatomical studies of corticotropin-releasing factor (CRF)-like immunoreactivity in rat brain have reported prominent clustering of neuronal elements containing this peptide within the amygdala. The highest concentrations of both CRF-positive cells and fibers were evident in the central nucleus, an observation consistent with the putative role of this peptide in autonomic and endocrine regulation. In addition, lower densities of CRF-positive somata and processes have been noted in other amygdaloid nuclei. However, the distribution of CRF-like immunoreactivity in the amygdala has not been described for any primate species. Such a description would be of interest since substantial differences in the distribution of CRF in rodent and primate have been reported for other brain regions. The present study uses immunohistochemical methods, with a polyclonal antiserum directed against the human form of CRF, to determine the distribution of this peptide in non-colchicine-treated monkeys (Saimiri sciureus). Within the amygdaloid complex, the most numerous and concentrated collections of CRF-positive neurons were seen in the basal and lateral nuclei. The highest densities of CRF-positive fibers and terminals were seen in the lateral and central amygdaloid nuclei. Moderately dense plexuses of CRF-positive fibers also were seen in layer Ia of the periamygdaloid cortex, nucleus of the lateral olfactory tract, anterior and posterior cortical nuclei, and the medial nucleus. Thus, the distribution of CRF-like immunoreactivity differs substantially in monkey and rat amygdala. Since CRF-positive perikarya in monkey are most prominent in nuclei with pronounced interconnections with neocortex, these differences may be an integral component of the increased cortical development that characterizes the primate brain. PMID- 1430318 TI - Lucifer yellow, retrograde tracers, and fractal analysis characterise adult ferret retinal ganglion cells. AB - The dendritic morphology of retinal ganglion cells in the ferret was studied by the intracellular injection of lucifer yellow in fixed tissue. Ganglion cells were identified by the retrograde transport of red or green fluorescent microspheres that had been injected into different target nuclei, usually the lateral geniculate nucleus or superior colliculus. This approach allows the comparison of dendritic morphologies of ganglion cells in the same retina with different central projections and also identifies cells with branching axons. The digitised images of dendritic arbors were analysed quantitatively by a variety of measures. Dendritic complexity was assessed by calculating the fractal dimension of each arbor. The ferret has distinct alpha, beta, and gamma morphological classes of cells similar to those found in the cat. The gamma cell class was morphologically diverse and could be subdivided into "sparse," "loose," and "tight" groups, reflecting increasing dendritic complexity. Whereas the beta cell projection was limited to the lateral geniculate nucleus alone, alpha and gamma cells could project to either or both nuclei. Retinal ganglion cells labelled from the pretectal nuclei formed a morphologically distinct class of retinal ganglion cells. The ipsilateral projection lacked alpha cells and the most complex, "tight" gamma cells. However, ipsilaterally projecting "loose" gamma cells overlapped alpha cells in both soma and dendritic dimensions. Different morphological classes of retinal ganglion cells hence show characteristic axon behaviour both in their decussation at the chiasm and in which targets they innervate. Fractal measures were used to contrast variation within and between these identified classes. PMID- 1430319 TI - The shell region of the nucleus ovoidalis: a subdivision of the avian auditory thalamus. AB - The connectivity of a region surrounding the established thalamic auditory nuclei, n. ovoidalis (Ov) and n. semilunaris parovoidalis (SPO), was explored in the ring dove by using the anterograde tracers, Phaseolus vulgaris leucoagglutinin (PHAL) and biocytin, and the retrograde tracer, fluorogold. The Ov-SPO surround received a projection from a cell group along the interface of the auditory midbrain and the n. intercollicularis, as revealed with PHAL and biocytin, and was composed of neurons exhibiting a common morphology. These features and the presence of overlapping projections from different portions of the Ov-SPO surround suggest that this region comprises a functionally discrete area, which we term the Ov shell. Single unit recording within the shell established the existence of acoustically responsive units. Both PHAL and fluorogold labeling revealed a robust projection from the Ov shell to the caudomedial hypothalamus. Major telencephalic projections of the shell terminated within the ventral paleostriatal complex, "end-zones" of the field L, the caudomedial hyperstriatum ventrale, and regions immediately dorsal and lateral to the auditory neostriatum. Except for a portion of the shell bordering medial ovoidalis, PHAL injections into the shell also labeled fibers within the caudolateral neostriatum and along the lateral neostriatal rim. The connectivity of the Ov shell suggests that this region may integrate auditory pathways with brain regions associated with endocrine mediated behavior. In addition, the shell may constitute a source of converging input to several levels of central auditory pathways. PMID- 1430320 TI - Development of the olivocerebellar projection in the rat: I. Transient biochemical compartmentation of the inferior olive. AB - In the present study the early phases of the development of the inferior olive were examined by using immunocytochemical techniques. We observed that, from embryonic day 16 onward, antibodies against the calcium binding proteins parvalbumin and calbindin and the calcitonin gene related peptide stain partially overlapping territories of the inferior olive. This staining delimits a biochemical zonation of the inferior olive which is combinatory and transient. We have previously observed a biochemical parcellation of the cerebellar Purkinje cells which, like that of the inferior olive, is first observed at E16, involves the combined expression of marker proteins and is also transient. In order to know whether the biochemical compartmentations of the cerebellum and inferior olive arise independently, the time course of the development of the olivocerebellar projection was studied by anterograde and retrograde in vitro axonal tracing by using the fluorescent carbocyanine dye DiI. The olivocerebellar axons were found to reach the limit of the cerebellar plate at E16 and to enter it at E17. Even at this age the great majority of the climbing fibers are tightly fasciculated, which minimizes their interactions with the PC clusters. These observations indicate that the topographical heterogeneity of Purkinje cells and inferior olive neurons arise independently. The transient biochemical individualization of subgroups of neurons during development could contribute to recognition mechanisms. PMID- 1430321 TI - Development of the olivocerebellar projection in the rat: II. Matching of the developmental compartmentations of the cerebellum and inferior olive through the projection map. AB - A transient biochemical parcellation has been observed by immunocytochemical methods, during the perinatal development of both the inferior olive and the cerebellum. In the present study, we sought a relationship between this developmental compartmentation and the organization of the olivocerebellar projection. In the inferior olive, a transient parvalbumin immunoreactivity restricted to the dorsal cap of the medial accessory olive is observed around birth. The climbing fiber projection of the dorsal cap was identified in the cerebellum of newborn rats based on its parvalbumin immunoreactivity. The pattern of this projection, restricted to lobules IX and X of the vermis, and to the flocculus, is indistinguishable from that of the adult medial accessory olive, which was previously described from axonal tracing experiments. The parvalbumin immunoreactive climbing fibers were followed between birth and postnatal day 7. In the caudal vermis, Purkinje cell subpopulations can be identified between embryonic day 20 and postnatal day three, on the basis of their differential immunostaining with an antibody directed against a specific peptide, PEP 19. In lobule X, the parvalbumin immunoreactive climbing fibers form two sagittal bands on each side of the midline, one medial and one lateral. The medial parvalbumin immunoreactive climbing fiber band is coextensive with a PEP 19 negative Purkinje cell cluster, indicating a clear relationship between the biochemical parcellations of the cerebellum and inferior olive. PMID- 1430322 TI - Myelin-axon relationships in the rat phrenic nerve: longitudinal variation and lateral asymmetry. AB - It is known that the myelin sheath thickness-axon perimeter relationship varies between peripheral nerves. This study examines the possibility that that relationship may vary between levels along a given nerve or between corresponding levels of the right and left examples of the same nerve. The relationship is examined for large and small fibre classes at well separated upper and lower intrathoracic levels in the rat phrenic nerve. The study shows that the myelin axon relationship differs between levels along the same nerve bundle in the same (intrathoracic) environment. Thus, for a given increase in the perimeter of large axons, sheath thickness increases significantly more at lower than at upper levels. In addition, myelin sheath thickness shows a statistically significant lateral asymmetry in favour of the left side for the large fibre class at the upper thoracic level. The setting of the myelin sheath thickness-axon perimeter relationship also differs between the large and small fibre classes at each level examined. Large fibres have proportionately thicker sheaths than small fibres and this difference is reflected in the significantly smaller g-ratio of the former. Systematic differences in the setting of the myelin sheath thickness-axon perimeter relationship between large and small fibre classes may be a widely occurring phenomenon. It may be concluded that the myelin-axon relationship varies significantly both within and between nerves and also between fibre classes. Accordingly, morphometric studies of normal or pathological nerves should take into account possible consistent longitudinal variation or lateral asymmetry in fibre parameters and myelin-axon relationships within a given nerve bundle or fibre class, in order to avoid introducing systematic bias and to minimize variance between samples. PMID- 1430323 TI - Time of origin of cortico-collicular projection neurons in the rat visual cortex. AB - The time of origin and the radial gradient of neurogenesis of cortico-collicular neurons have been studied in the rat visual area 17. We used a combined technique for the histochemical detection of the retrogradely transported horseradish peroxidase from the superior colliculus and the autoradiographic detection of the [3H]-thymidine administered during the gestational period. The cortico-collicular neurons of visual area 17 are located in layer V and are generated on gestational day (GD) 15 (59.78%), GD 16 (36.21%), and GD 17 (4.01%). This finding reveals that, for the cortico-collicular neuronal population, the birth date is well correlated with the laminar position in the adult animal. To see whether the cortico-collicular neurons located at various radial levels of layer V are generated concurrently, or whether they follow an "inside-out" pattern of positioning, we divided layer V into three (upper, middle and lower) sublaminae. Most cortico-collicular neurons located in the lower two-thirds of layer V are generated on GD 15 (65%), whereas the neurons located in the upper third of the layer are generated both on GD 15 and GD 16 in almost equal proportions (52.53% and 44.39%, respectively). PMID- 1430324 TI - Effects of sex and androgen treatment on dendritic dimensions of neurons in the sexually dimorphic preoptic/anterior hypothalamic area of male and female ferrets. AB - A sexually dimorphic group of cells at the dorsal border of the preoptic/anterior hypothalamic area (POA/AH) of ferrets has been previously identified in Nissl stained tissue. In this study, Golgi-stained tissue was examined in order 1) to determine whether sex differences exist in dendritic dimensions of neurons from this region, and 2) to assess the effects of adult androgen treatment on dendritic morphology in ferrets of both sexes. Brains from adult ferrets given daily injections of testosterone propionate (5 mg/kg body weight) or oil vehicle for 5 weeks after gonadectomy were impregnated by Golgi-Cox procedures. After sectioning at 120 microns, 78 multipolar neurons were selected from the sexually dimorphic POA/AH of 12 ferrets and reconstructed in three dimensions with the aid of a computer-assisted neuron tracing system. Large sex differences were observed in somal area and most aspects of dendritic morphology, including total length, number of branches, and total dendritic surface area. Androgen also appeared to accentuate dendritic arborization in both sexes, but this effect was weaker than the sex effect, more apparent in males than females, and restricted to fewer variables. The most statistically significant effects of adult androgen treatment in males were found for total dendritic surface area and percentage of fourth order dendrites, and in females, average dendritic thickness. These data show that strong sex differences exist in dendritic structure of neurons in the POA/AH, and suggest that alterations in levels of gonadal steroids in adulthood may promote synaptic remodeling in a region of the brain involved in the control of sexually dimorphic behaviors. PMID- 1430325 TI - Projections from the lateral nucleus to the basal nucleus of the amygdala: a light and electron microscopic PHA-L study in the rat. AB - A recent study, carried out in the monkey brain demonstrated a hitherto undescribed projection from the lateral to the basal nucleus of the amygdaloid complex. In the present study, we used light and electron microscopic techniques to determine whether a similar connection exists in the rat brain and to define what type(s) of synaptic contacts are produced by fibers of this projection. Injections of the lectin tracer Phaseolus vulgaris leucoagglutinin (PHA-L) were placed into several levels of the lateral nucleus and the distribution of fibers in the basal (basolateral) nucleus was evaluated. All lateral nucleus injections resulted in labeled fibers in the basal nucleus, though the density and distribution of labeled fibers depended on the position of the injection site within the lateral nucleus. In general, the heaviest labeling of the basal nucleus was observed after injections at midrostrocaudal levels of the lateral nucleus, especially when the injection was located ventrally. Fibers originating from cells labeled by these injections were observed throughout much of the rostrocaudal extent of the basal nucleus. Rostrally situated injections resulted in substantially lower levels of labeled fibers in the basal nucleus. Injections placed caudally in the lateral nucleus resulted in light to medium levels of labeled fibers in the basal nucleus; the terminal field in these cases did not extend as far rostrally as after the rostral and midlevel injections. Electron microscopic analysis of PHA-L labeled fibers revealed that they contributed synapses to the basal nucleus. The majority of PHA-L labeled terminals formed asymmetric contacts on dendritic spines or shafts; a smaller number of PHA-L labeled terminals formed symmetrical synapses. PMID- 1430326 TI - Photic regulation of Fos-like immunoreactivity in the suprachiasmatic nucleus of the mouse. AB - In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus functions as the primary pacemaker of the circadian system. Light has been shown to induce Fos like immunoreactivity (Fos-LI) in the SCN of rats and hamsters. The purpose of the present study was to evaluate extensively the effect of light on Fos-LI in the mouse SCN. Brief pulses of light administered to animals otherwise in constant darkness were found to induce Fos-LI. This photic induction was unaffected by the rd mutation, which causes the profound loss of photoreceptors but fails to affect circadian responses to light. Light regulation of Fos-LI was dependent upon the phase of the circadian cycle in which the light pulse was administered. Phases at which light causes phase shifts of the circadian system were permissive for Fos-LI induction (CT 16 and 24), while phases in which light does not cause phase shifts were not permissive (CT 6 and 9). The time course of the induction at CT 16 was also described. In a light/dark cycle, Fos-LI was found to be rhythmically expressed with Fos-LI elevated soon after the lights came on but remaining low throughout the rest of the cycle. However, this rhythm is a direct consequence of the light because in constant darkness Fos-LI was always low. These results have implications regarding the possible functional roles of Fos in the circadian system and add to our understanding of light regulation of circadian physiology in the mouse. PMID- 1430327 TI - Connections of the posterior nucleus of the amygdala. AB - The connections of a relatively homogeneous band of neurons in the caudal amygdala have been examined with anterograde and retrograde axonal tracing methods in the rat. This region, called here the posterior nucleus of the amygdala (PA), corresponds in part to an area that has been referred to as the cortico-amygdaloid transition area, posterior part of the medial nucleus of the amygdala, amygdalo-hippocampal transition area, and posteromedial basal nucleus. Experiments with fluorogold and phaseolus vulgaris leucoagglutinin (PHAL) indicate that the major neuronal input to the PA arises in the ventral premammillary nucleus, and that substantial projections also arise in olfactory related areas such as the medial nucleus of the amygdala, bed nucleus of the accessory olfactory tract, and posterior cortical nucleus of the amygdala, as well as in the ventral subiculum and adjacent parts of hippocampal field CA1. Other seemingly minor inputs, including cholinergic fibers from the substantia innominata, dopaminergic fibers from the ventral tegmental area, and serotoninergic fibers from the dorsal nucleus of the raphe, were also identified. The efferent projections of the PA as determined with the PHAL method appear to follow five major routes: 1) a relatively small group of laterally directed fibers innervates the dorsal endopiriform nucleus, and a few of these fibers reach cortical area TR and the lateral entorhinal area; 2) another small group of fibers courses medially to innervate the ventral subiculum and adjacent parts of field CA1; 3) many fibers course ventrally to innervate the outer molecular layer of the medial part of the posterior cortical nucleus of the amygdala; 4) a moderate group of fibers courses rostrally to innervate primarily the posterodorsal part of the medial nucleus of the amygdala, although some fibers continue on to end less densely in rostral parts of the medial nucleus of the amygdala before leaving the amygdala through the ansa peduncularis; and 5) the major output of the PA courses through the stria terminalis. One branch of this pathway massively innervates the principal nucleus of the bed nuclei of the stria terminalis before entering the medial hypothalamus, where it ends massively in the anteroventral periventricular and medial preoptic nuclei, ventrolateral part of the ventromedial nucleus and adjacent parts of the basal lateral hypothalamic area, and ventral premammillary nucleus. The other branch sends fibers to the ventral lateral septal nucleus, nucleus accumbens, olfactory tubercle, and infralimbic area of the prefrontal cortex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1430328 TI - Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat. AB - The projections of the ventral subiculum are organized differentially along the dorsoventral (or septotemporal) axis of this cortical field, with more ventral regions playing a particularly important role in hippocampal communication with the amygdala, bed nuclei of the stria terminalis (BST), and rostral hypothalamus. In the present study we re-examined the projection of the ventral subiculum to these regions with the Phaseolus vulgaris leucoagglutinin (PHAL) method in the rat. The results confirm and extend earlier conclusions based primarily on the autoradiographic method. Projections from the ventral subiculum course either obliquely through the angular bundle to innervate the amygdala and adjacent parts of the temporal lobe, or follow the alveus and fimbria to the precommissural fornix and medial corticohypothalamic tract. The major amygdalar terminal field is centered in the posterior basomedial nucleus, while other structures that appear to be innervated include the piriformamygdaloid area, the posterior basolateral, posterior cortical, posterior, central, medial, and intercalated nuclei, and the nucleus of the lateral olfactory tract. Projections from the ventral subiculum reach the BST mainly by way of the precommissural fornix, and provide rather dense inputs to the anterodorsal area as well as the transverse and interfascicular nuclei. The medial corticohypothalamic tract is the main route taken by fibers from the ventral subiculum to the hypothalamus, where they innervate the medial preoptic area, "shell" of the ventromedial nucleus, dorsomedial nucleus, ventral premammillary nucleus, and cell-poor zone around the medial mammillary nucleus. We also observed a rather dense terminal field just dorsal to the suprachiasmatic nucleus that extends dorsally and caudally to fill the subparaventricular zone along the medial border of the anterior hypothalamic nucleus and ventrolateral border of the paraventricular nucleus. The general pattern of outputs to the hypothalamus and septum is strikingly similar for the ventral subiculum and suprachiasmatic nucleus, the endogenous circadian rhythm generator. PMID- 1430329 TI - Projections of the ventral premammillary nucleus. AB - The projections of the ventral premammillary nucleus (PMv) have been examined with the Phaseolus vulgaris leucoagglutinin (PHAL) method in adult male rats. The results indicate that the nucleus gives rise to two major ascending pathways and a smaller descending pathway. One large ascending pathway terminates densely in most regions of the periventricular zone of the hypothalamus, with the notable exception of the suprachiasmatic, suprachiasmatic preoptic, and median preoptic nuclei. This pathway is in a position to influence directly many cell groups known to regulate anterior pituitary function. The second large pathway ascends through the medial zone of the hypothalamus and densely innervates the ventrolateral part of the ventromedial nucleus and adjacent basal parts of the lateral hypothalamic area, medial preoptic nucleus, principal nucleus of the bed nuclei of the stria terminalis, ventral lateral septal nucleus, posterodorsal part of the medial nucleus of the amygdala, posterior nucleus, and immediately adjacent regions of the posterior cortical nucleus of the amygdala. It is already known that these regions are major components of the sexually dimorphic circuit, and, interestingly, that they provide the major neural inputs to the PMv. The smaller descending projection from the PMv seems to innervate preferentially the posterior hypothalamic nucleus, although a small number of fibers appear to end in the tuberomammillary nucleus, supramammillary nucleus, specific regions of the medial mammillary nucleus, interfascicular nucleus, interpeduncular nucleus, periaqueductal gray, dorsal nucleus of the raphe, laterodorsal tegmental nucleus, Barrington's nucleus, and locus coeruleus. Relatively sparse terminal fields associated with ascending fibers were also observed in the dorsomedial nucleus of the hypothalamus; in the nucleus reuniens, parataenial nucleus, paraventricular nucleus of the thalamus, and mediodorsal nucleus; in the central nucleus of the amygdala, anterodorsal part of the medial nucleus of the amygdala, posterior part of the basomedial nucleus of the amygdala; and in the ventral subiculum and adjacent parts of hippocampal field CA1, and the infralimbic and prelimbic areas of the medial prefrontal cortex. Taken as a whole, the evidence suggests that the PMv receives two major inputs--one from the sexually dimorphic circuit, and the other from the blood in the form of gonadal steroid hormones--and gives rise to two major outputs: one (perhaps feed-forward) to the neuroendocrine (periventricular) zone of the hypothalamus, and the other (perhaps feed-back) to the sexually dimorphic circuit. PMID- 1430330 TI - Embryonic development of synapses on spiking local interneurones in locust. AB - The development of synapses on an identified population of spiking local interneurones in the thoracic ganglia of embryonic locusts was examined by means of intracellular horseradish peroxidase injection and electron microscopy. In adult locusts, spiking local interneurones of the midline group receive direct inputs onto a ventral field of branches from leg mechanosensory afferents and in turn make output synapses, mainly from a dorsal field of branches, directly upon leg motor neurones, nonspiking local interneurones, and intersegmental interneurones. The aim of this study is to examine the development of these connections. These interneurones are born relatively late in embryogenesis and are not identifiable until approximately 55% of development. At this time (55 60%) only simple filopodial contacts or punctate contacts are evident between the stained interneurones and other neurones. By 65-70% embryogenesis, vesicles are found adjacent to regions where apposed membranes are symmetrically thickened with amorphous electron-dense material. These symmetrical contacts lack distinct presynaptic bar-shaped densities and therefore, are not considered to be synapses. At this stage, the interneurones do not produce action potentials upon intracellular injection of depolarising current. Morphologically identifiable synapses, with vesicles, a presynaptic bar, and relatively little postsynaptic density, are first evident at 70-75%, coincident with the time of arrival of the majority of leg mechanosensory afferents into the central nervous system. At this stage, action potentials and synaptic potentials are also recorded for the first time. The midline spiking interneurones thus become electrically excitable when synapses are first recognisable, at approximately 70% embryogenesis. Most of the synapses found on the interneurones are outputs. The ratio of outputs to inputs on ventral branches is 7.5:1 which contrasts markedly to the adult ratio of 1:2. By 85-90%, output synapses still predominate on the ventral branches, but the ratio of outputs to inputs is reduced to almost 2:1. Dorsal branches have predominantly output synapses throughout embryogenesis. The ratio of dorsal outputs to inputs at 85-90% is 8.5:1 which compares with the adult ratio of 6.5:1. At this stage, action potentials and synaptic activity are always recorded. PMID- 1430331 TI - Topographic organization of cortical and subcortical projections to posterior cingulate cortex in the cat: evidence for somatic, ocular, and complex subregions. AB - The posterior cingulate area (CGp) of the cat consists of cortex on the exposed cingulate gyrus and in the adjacent ventral bank of the splenial sulcus. We have placed deposits of distinguishable fluorescent tracers at multiple restricted sites in CGp and have analyzed the distribution throughout the forebrain of neurons labeled by retrograde transport. Cortical projections to CGp arise (in approximately descending order of strength) from anterior cingulate cortex; prefrontal cortex and premotor areas including the frontal eye fields; visual areas including especially areas 7 and 20b; parahippocampal areas; insular cortex; somesthetic areas; and auditory areas. Corticocortical pathways are organized topographically with respect to the posterior-anterior axis in CGp. Projections from prefrontal cortex and other areas with complex (as opposed to sensory, motor, or limbic) functions are concentrated posteriorly; projections from visual and oculomotor areas are concentrated at an intermediate level; and projections from areas with somesthetic and somatomotor functions are concentrated anteriorly. Thalamic projections to CGp arise from the anterior nuclei (AD, AV, and AM), from restricted portions of the ventral complex (VAd, VAm, and VMP), from discrete sectors of the lateral complex (LD, LPs, and LPm), from the rostral crescent of intralaminar nuclei (CM, PC, and CL), and from the reuniens nucleus. Projections from AM, VAd, LD, and LPs are spatially ordered in the sense that more ventral thalamic neurons project to more anterior cortical sites. Projections from AV and AD are stronger at more posterior cortical sites but do not show other signs of topographic ordering. Projections from LPm, CM, PC, CL, and RE are diffuse. We conclude (1) that cortical afferents of CGp derive predominantly from neocortical areas including those with well established sensory and motor functions; (2) that limbic projections to CGp originate primarily in structures, including the hippocampus, which are associated with memory, as opposed to structures, including the amygdala, which are associated with emotional and instinctual behavior; and (3) that CGp contains subregions in which complex, ocular, or somatic afferents predominate. PMID- 1430332 TI - Acetylcholinesterase reactivity in the frontal cortex of human and monkey: contribution of AChE-rich pyramidal neurons. AB - Light and electron microscopic histochemistry were used to analyze the distribution of the enzyme acetylcholinesterase (AChE) in the frontal cortex of macaque monkey and human. In prefrontal, premotor, prelimbic, and medial paralimbic areas, AChE reactivity showed a characteristic bilaminar appearance due to a combination of positive neuronal and fiber labeling in deep layer III and layer V. In addition, layer I contained dense AChE-reactive fiber plexuses labeled throughout the frontal areas. One of the major issues addressed in this study was whether pyramidal neurons in the nonhuman primate cortex express AChE reactivity, as has been reported for humans. Three different histochemical methods were applied to provide confidence in the reliability of the results. Light microscopic analysis revealed strongly reactive, intensely stained pyramidal neurons in monkey as well as in the human. Further, these AChE-rich neurons exhibited the same pattern of laminar and regional variation in both species. In the prefrontal and premotor areas, AChE-rich pyramidal neurons predominated in layer III. In the motor cortex, they were also concentrated in layer III, but numerous AChE-rich pyramids were observed in layer V. In contrast, medial paralimbic areas had more AChE-rich neurons in layer V than in layer III. Finally, at the electron microscopic level, the subcellular distribution of AChE histochemical product in pyramidal neurons was identical in both monkey and human. The only difference noted between the two species was that the density of AChE-rich pyramidal neurons was greater in humans than in monkeys. Since nonhuman primates possess a system of AChE-reactive pyramidal neurons similar to human, they provide a potentially useful animal model for analyzing acetylcholinesterase neuronal systems in the cortex, which are compromised in various neuropathological diseases like Alzheimer's disease. PMID- 1430333 TI - Normal development and effects of neonatal infraorbital nerve damage upon the innervation of the trigeminal brainstem complex by primary afferent fibers containing calcitonin gene-related peptide. AB - Immunocytochemistry was used to study the normal development and response to infraorbital nerve (ION) damage of the innervation of the trigeminal (V) brainstem complex by axons recognized by an antibody directed against calcitonin gene-related peptide (CGRP). CGRP-like immunoreactivity (CGRPLI) was present in axons that occupied the outer V spinal tract (TrV) at all levels of the V brainstem complex. Almost no fibers terminated within V nucleus principalis (PrV), but there was dense CGRPLI in the supratrigeminal nucleus. There was also very little CGRPLI within rostral V subnucleus oralis (SpO). However, in the caudal one-half of the nucleus, a dense elongated patch of immunoreactivity was consistently present just medial to TrV. Only occasional CGRP-positive axons could be seen within V subnucleus interpolaris (SpI), but the paratrigeminal nucleus contained dense immunoreactivity. Trigeminal subnucleus caudalis (SpC) also contained CGRPLI that was very dense in lamina I and the outer portion of lamina II. Scattered terminals were also present in layers III and IV and dense terminal clusters were in lamina V. CGRP-immunoreactive neurons were present in the V ganglion by embryonic (E-) day 16 and immunoreactive axons could be seen in the V brainstem complex on E-17. At birth, CGRP-positive axons in the V brainstem complex had achieved a distribution very similar to that in adult rats. The major difference between the patterns of labelling in neonates and adults was the presence of relatively large numbers of CGRP-positive fibers in ventral PrV and SpO of the former animals. The disappearance of these fibers was completed by the middle of the third postnatal week. Transection of the ION on the day of birth had little effect upon CGRP in SpO, SpI, and SpC, but it did result in an increase in CGRP-positive fibers in PrV ipsilateral to the damaged nerve. When considered together with previous findings, these results suggest that CGRP positive axons express this peptide well after they have entered the V brainstem complex and that the central terminal field of these fibers is not substantially altered by a manipulation which results in the death of nearly 60% of all V primary afferent neurons. PMID- 1430334 TI - The superficial plexiform layer: a third retinal association area. AB - Electron microscopy enables the identification of a new association area in the mammalian retina. It is a region whose processes and synaptic junctions form a diffuse and intermittent layer bridging the boundary between the optic nerve fibre layer and ganglion cell layer. It involves displaced amacrine cells, retinal ganglion cells and probably interplexiform cell processes. Because it is close to the vitreal surface of the retina and has several properties of a plexiform layer, it has been named the superficial plexiform layer. It is much more sparse than the outer or inner plexiform layers in the rabbit, but contains a significant and substantial density of 6,100 synapses/mm2 near the visual streak. Morphological criteria distinguish two classes of synapses in the new association area. One has features of Colonnier's symmetric type and is formed by amacrine-like processes or their terminals, onto other amacrine-like processes or the cell bodies, dendrites and axon hillocks of some large ganglion cells. It makes up 79% of the population at a density of 4,800 synapses/mm2 in the examined sample. The second class arises from large processes of the fibre layer, which resemble axons rather than amacrine cell branches, has Colonnier's asymmetric form, and synapses onto a variety of other neuronal processes and cells. At a local density of 1,300/mm2 this type forms 21% of the population. A series of experiments including Wallerian degeneration, retrograde degeneration, electron microscopy and horseradish peroxidase (HRP) transport was employed to determine the nature of the large synapse-forming processes of the fibre layer that were the most amenable to investigation. It is concluded that the processes project into the optic nerve because they can be filled with HRP by retrograde transport from the end of the transected optic nerve. Although this result is based on limited evidence, it is complemented by the observation that the majority of the fibres undergo retrograde degeneration within 25 days of optic nerve section. It is concluded that the processes are either centrifugal fibres or the axons of retinal ganglion cells. The persistence of a relatively normal density of synapse forming large fibres for seven days after optic nerve section, without Wallerian degeneration, argues that they are not the terminals of centrifugal axons. This conclusion is complemented by a separate class of profiles that did degenerate in this short period and are concluded to represent the centrifugal fibres. The large synapsing processes of the fibre layer are concluded to be the axons of some large ganglion cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1430335 TI - Projections to the medial superior olive from the medial and lateral nuclei of the trapezoid body in rodents and bats. AB - In this study we present direct evidence of axonal projections from both the medial and lateral nuclei of the trapezoid body to the medial superior olive. Projections were traced by intracellularly labeling cells and axons in a tissue slice preparation of two rodent species, Mus musculus and Meriones unguiculatus and two bat species, Eptesicus fuscus and Pteronotus parnellii. The main axon of most principal cells in the medial nucleus of the trapezoid body gives off one or more collateral branches which arborize within the medial superior olive. These collateral axons form small bouton-like swellings which primarily contact somata within the central cell column in the medial superior olive. Likewise, labeled elongate and multipolar cells of the lateral nucleus of the trapezoid body send axons to both the medial and lateral superior olives. These axons also form perisomatic contacts in both target nuclei. These two sets of projections may relay ascending input to the medial superior olive and the lateral superior olive; the medial nucleus of the trapezoid body is known to relay input from the contralateral ventral cochlear nucleus, and the lateral nucleus of the trapezoid body may relay input from the ipsilateral ventral cochlear nucleus. These projections offer two routes for indirect, possibly inhibitory input to reach the medial superior olive from both cochlear nuclei. These indirect, inhibitory pathways may parallel the direct excitatory projections the medial superior olive receives from each cochlear nucleus. PMID- 1430336 TI - Ultrastructural development of the medial superior olive (MSO) in the ferret. AB - When ferrets are born, four weeks before the onset of hearing, few synapses are evident in the medial superior olive (MSO). The synapses present are immature and almost exclusively found in the neuropil. The MSO somata are virtually devoid of synaptic contacts but are contacted by fine glial processes that increasingly ensheathe the somata during the first postnatal week. By P12, somatic synaptogenesis in the MSO is evident. Initially the terminals contain vesicles of irregular shape, size, and distribution. The glial lamellae appear to withdraw as the synaptic contacts form but continue to cover the asynaptic portions of the cell surface. The lamellae frequently extend from ensheathing the soma to encapsulate the immature terminals. During the next two weeks, synaptic density and terminal encapsulation proceed until the somata is surrounded by encapsulated synaptic terminals as in the adult ferret MSO. While most immature terminals contain round vesicles, during the first postnatal week some terminals with nonround vesicles can be distinguished. The first distinction between types of nonround vesicle-containing terminals, i.e., pleiomorphic and ovoid, is in the second postnatal week. This distinction becomes increasingly clear and by the end of the first postnatal month, terminal types can be reliably categorized. These observations indicate that: (1) synapses are present in the MSO neuropil one month prior to the onset of hearing, (2) the major period of synaptogenesis begins approximately two weeks prior to the onset of hearing, and (3) glial lamellae ensheathe MSO somata prior to the onset of somatic synaptogenesis, withdraw as synapses form, and subsequently re-extend to encapsulate newly formed synapses. PMID- 1430337 TI - Early postnatal alcohol exposure acutely and permanently reduces the number of granule cells and mitral cells in the rat olfactory bulb: a stereological study. AB - This study demonstrates that exposure to alcohol during a period of rapid brain growth can lead to severe and permanent deficits in the number of granule cells and mitral cells in the main olfactory bulb. Sprague-Dawley rat pups were reared artificially and were administered alcohol over postnatal days (PD) 4 through 9, a period of brain development comparable to part of the human third trimester. The daily alcohol dose of 6.6 g/kg was concentrated into two of the twelve daily feedings, producing high peak blood alcohol concentrations followed by near total clearance. Pups were either sacrificed on PD10 or were allowed to grow to adulthood and sacrificed on PD115. The total number of granule cells and mitral cells in the main olfactory bulb were estimated with the aid of unbiased stereological principles and systematic sampling techniques. Exposure to alcohol resulted in significant reductions in the number of both granule cells and mitral cells on PD10. Significant deficits in both neuronal populations remained on PD115. The results support the hypothesis that alcohol exposure can kill developing neurons and lead to permanent neuronal deficits. Substantial developmental changes also occurred in the total number of mitral cells and granule cells between PD10 and PD115 in the control groups. In untreated rats, the number of granule cells increased from 2.20 x 10(6) on PD10 to 5.06 x 10(6) on PD115, while the number of mitral cells decreased from 5.30 x 10(4) to 4.33 x 10(4) over the same time period. These results demonstrate that there is a natural loss of mitral cells during postnatal development at the same time that granule cell number is increasing. PMID- 1430338 TI - Distribution of the peptide Ala-Pro-Gly-Trp-NH2 (APGWamide) in the nervous system and periphery of the snail Lymnaea stagnalis as revealed by immunocytochemistry and in situ hybridization. AB - Immunocytochemistry and in situ hybridization were used to identify 200-250 central neurons that synthesize and contain the peptide APGWamide in the central nervous system of Lymnaea. The majority of these cells reside within the right anterior lobe of the cerebral ganglion and most appear to have projections to the ventral lobe of the ganglion. The neurites then branch to innervate the lobe and to send further projections into the penial nerve and to the PeIb cluster of the right pedal ganglion. The right ventral lobe also contains a cluster of about 30 40 somata, which apparently synthesize and contain APGWamide. Other populations of cells found in both the right and left anterior lobes project ipsilaterally to the pleural, parietal, and visceral ganglia. Prominent somata are also located in clusters in the visceral and right parietal ganglia. These cells project ipsilaterally into caudal neuropilar regions of the cerebral ganglia. Peripheral projections of central neurons form a dense plexus of varicose, APGWamide containing fibres in superficial layers of the penis and preputium. Other peripheral projections were noted in the prostate and vas deferens. No peripherally located cell bodies appeared to contain or synthesize the peptide. The results show that APGWamide is widely present in the central nervous system and male reproductive organs and suggest that it plays a major role in control of reproduction. PMID- 1430339 TI - Immunocytochemical identification of primary olfactory afferents in rainbow trout. AB - We have used a combination of techniques to analyze the primary olfactory projection in trout: anterograde tract tracing with horseradish peroxidase (HRP) and immunocytochemistry with antisera to olfactory marker protein (OMP) and to keyhole limpet hemocyanin (KLH). HRP labeling and the OMP antiserum revealed a subset of ciliated receptor neurons with a wide dendrite that lacked the protruding knob found on other receptor neurons. The organization of the primary olfactory axons was clearly revealed by antisera to KLH, which reacted with no other neurons. When visualized with anti-KLH, fascicles of olfactory axons penetrated the basal lamina of the olfactory rosette at scattered sites and converged to form the olfactory nerve. Fascicles within the olfactory nerve traveled parallel to the long axis of the nerve until resorted by extensive intermixing as they entered the olfactory bulb. Within the olfactory bulb, most axons terminated in nine discrete terminal fields in the glomerular layer; however, a few olfactory nerve axons projected into the ventral medial telencephalon. Fascicles supplying each terminal field in the glomerular layer followed distinctive trajectories within the olfactory nerve layer. Axons ending in two terminal fields made brush-like terminations rather than the glomerular terminations characteristic of the remaining seven fields. After unilateral olfactory nerve transection, returning olfactory axons reestablished the normal pattern of terminal fields within 14 weeks. It is likely that the organization of afferents in the trout olfactory bulb is similarly well regulated during normal receptor cell replacement. PMID- 1430340 TI - Morphological types of ganglion cells in the dog and wolf retina. AB - The morphological types of ganglion cells in the dog and wolf retina were studied by intracellular staining with Lucifer Yellow. These retinae contain a range of ganglion cell types that closely correspond to those found in cat retina: alpha cells with large somata and large, relatively densely branched dendritic trees; beta cells with medium-sized somata and small, densely branched dendritic trees; and a variety of other types with smaller somata and varying dendritic branching patterns and dendritic field sizes. The correspondence of canine and cat ganglion cell types strengthens the view that there is a common set of ganglion cell types in carnivores. Alpha and beta cell dendritic trees of dog and wolf are monostratified in either the inner or the outer part of the inner plexiform layer, suggesting an on/off dichotomy in the response to light. Dendritic field sizes of dog alpha and beta cells increase from the central area to peripheral retina: alpha cell fields from 160-200 microns to about 1,100 microns diameter, and beta cell fields from 25 microns to about 360 microns diameter. These sizes are quantitatively very similar to those found in cat retina. The close qualitative and quantitative morphological correspondence of cat and dog ganglion cells suggests that they are also functionally very similar. It is likely that dog alpha cells have brisk-transient (Y), and dog beta cells brisk-sustained (X) concentric receptive fields. From the smallest beta cell sizes it is concluded that the visual acuity of the dog may be as good as that of the cat. PMID- 1430341 TI - Heterogeneity of sensory hair cells in a fish ear. AB - The ultrastructure of sensory hair cells in the utricle of the cichlid fish, Astronotus ocellatus, the oscar, was studied by transmission electron microscopy of serial ultrathin sections from different regions of the epithelium. Two distinctly different types of hair cell were found, one located in the striolar region of the epithelium and the other in the extrastriolar region. Striolar hair cells have a well-defined perinuclear cisterna located just below the nucleus, and large perinuclear mitochondria. Synaptic bodies of striolar cells are small and located in clusters, while those in extrastriolar cells are relatively large and individually dispersed. The extrastriolar hair cell closely resembles the amniote type II hair cell. On the basis of these data, and consistent with earlier studies, it appears that the striolar hair cells closely resemble amniote type I hair cells in many significant ways. Thus we have called them type I-like cells. The extrastriolar hair cells appear to be typical of eighth nerve mechanoreceptors commonly described for fish and closely resemble the amniote type II hair cell. PMID- 1430342 TI - A microbiological, histopathological and immunohistological study of the intragastric inoculation of Listeria monocytogenes in mice. AB - The course of murine infection after intragastric inoculation of L. monocytogenes was investigated by immunocytochemical, histopathological and microbiological techniques. L. monocytogenes antigen was observed in epithelial cells of intestinal mucosa overlying Peyer's patches, but not in mucosa devoid of them. This suggests that penetration of L. monocytogenes into the host organism may take place through epithelium overlying Peyer's patches. The efficiency of bacterial penetration appeared to be low, as shown by the small amounts of L. monocytogenes antigen detected and the low counts of bacteria in organs. Gross or histopathological lesions in the intestinal tract were not observed. The presence of L. monocytogenes in spleen, liver and in maxillary and mesenteric lymph nodes, confirmed that the systemic course of infection by this route of inoculation is similar to that of the parenteral routes. The results emphasize the subclinical character of murine listeriosis by the oral route. PMID- 1430343 TI - Comparative histopathological study of rabbit haemorrhagic disease (RHD) and European brown hare syndrome (EBHS). AB - Histopathological lesions due to rabbit haemorrhagic disease (RHD) and European brown hare syndrome (EBHS) were studied in 35 rabbits and seven hares. Both rabbits (Oryctolagus cuniculus) and hares (Lepus europeus) regularly showed severe necrotizing hepatitis. In RHD, coagulation necrosis, mainly confined to the periphery of the lobules, was consistently found. In EBHS, lytic necrosis affecting the whole lobule was conspicuous, at least in severe cases. Particularly in EBHS, necrotic hepatocytes exhibited a special kind of karyorrhexis. In rabbits with a subacute or subclinical form of disease, early liver cirrhosis was observed. Depletion of lymphocytes was a regular feature in spleens of rabbits and was frequently found in hares. In RHD, disseminated intravascular coagulation (DIC) and haemorrhages in different organs, especially in kidneys and lungs were constant findings. DIC was never seen in EBHS and haemorrhages were an infrequent finding. PMID- 1430344 TI - Epithelioid sarcoma in a dog. AB - A tumour in an 11-year-old male crossbred Fox Terrier, showing the clinical and pathological features of epithelioid sarcoma in man is reported. Clinical aspects, location, peculiar pattern of spread and evolution, together with histopathological and immunohistological findings of this rare tumour simulating a granuloma are described. Controversial histogenesis is discussed. PMID- 1430345 TI - Cell-mediated immune response in rotavirus-infected calves: leucocyte migration inhibition assay. AB - The cell-mediated immune (CMI) response was determined in rotavirus-infected calves by leucocyte migration inhibition assay with blood, spleen, mesenteric lymph node and intestinal lymphocytes. The inhibition of migration was more prominent in intestinal and mesenteric lymph node lymphocytes than in spleen and blood. In rotavirus-infected calves, the assay indicated the presence of CMI response which was more prominent at the local site of infection. PMID- 1430346 TI - Detection of the binding of IgG2a and IgG2b on the surface of macrophages from mice chronically infected with lactic dehydrogenase virus. AB - This study showed that sera from mice chronically infected with lactic dehydrogenase virus (LDV) contained virus-antibody complexes (IC). IgG2a and IgG2b, but not IgG1, IgG3, IgM or IgA, were demonstrated on the surface of macrophages from chronically infected mice. These results suggest that IC in the circulation may bind to Fc receptors for IgG2a and IgG2b on the surface of macrophages and lead to the modulation of macrophage function seen in chronically LDV-infected mice. PMID- 1430347 TI - Effect of prostaglandin E2 on plasma lactic dehydrogenase activity in (NZB x NZW)F1 mice with a chronic infection of lactic dehydrogenase virus. AB - The effect of prostaglandin E2(PGE2) on blood LDH values was investigated in (NZB x NZW)F1 mice with or without an established infection with lactic dehydrogenase virus (LDV). Plasma LDH decreased in infected mice treated with PGE2, but increased in infected mice treated with indomethacin, an inhibitor of PGE2. However no significant effect on LDH occurred in uninfected mice treated with PGE2 or indomethacin. To investigate the mechanisms of decreased LDH activities resulting from treatment with PGE2, clearance tests were performed. Clearance of LDH-5, but not LDH-1, was faster in PGE2-treated mice than in non-treated mice, whether or not they were infected with LDV. The results suggest that enhanced clearance of LDH-5 in mice treated with PGE2 may account for the fall in plasma LDH in LDV-infected mice. PMID- 1430348 TI - Mycoplasma ovipneumoniae infection in Zimbabwean goats and sheep. AB - The prevalence of Mycoplasma ovipneumoniae (MO) in three Communal Lands flocks of goats on the outskirts of Harare is described. In a single sampling of nasal swabs from 172 randomly selected, apparently healthy goats, 112 animals were identified as carriers of MO. The three flocks had a history of occasional deaths, following chronic and subacute pneumonia associated with isolation of MO as the only identifiable pathogen. Attempts to induce clinical pneumonia in groups of 6 to 8-week-old kids and lambs with local isolates of MO were not successful. However, MO was consistently cultured from the trachea, lungs, lymph node and thymus of some test animals. Cuffing interstitial pneumonia was also observed in these animals. Infection of the thymus occurred; this has not previously been reported with any Mycoplasma sp. The animals did not produce detectable serum antibodies to MO nor were they reactive to MO antigen in a tuberculin-type hypersensitivity test. The possibility that a state of immunotolerance may have been responsible for failure to develop clinical pneumonia is discussed. PMID- 1430349 TI - Localization of African swine fever viral antigen, swine IgM, IgG and C1q in lung and liver tissues of experimentally infected pigs. AB - An immunohistological study was carried out on lungs and livers of pigs experimentally infected with two different African swine fever virus (ASFV) isolates. ASFV antigen, swine immunoglobulins (IgM and IgG) and (Clq) complement were demonstrated in both organs at different stages of infection. The ASFV antigen was mainly found in mononuclear phagocytic system (MPS) cells. Immunoglobulins and complement were observed in plasma, infected and non-infected phagocytic cells and cell debris. These findings suggest the presence, in acute infection, of immune complexes which may be involved in immunopathogenic mechanisms. PMID- 1430350 TI - Antibody response and antibody affinity maturation in cats with experimental proliferative immune complex glomerulonephritis. AB - An experimental model of proliferative glomerulonephritis (GN) in the cat, which closely resembles human proliferative forms of GN, has been used to study the role of antibody and antibody affinity in the development of immune complex mediated renal disease. The serum IgG and IgM antibody response to antigen, average antibody affinity (avidity) and affinity heterogeneity of the IgG and IgM populations was assessed at varying times after commencement of chronic immunization with the antigen, human serum albumin (HSA), by enzyme immunoassay. Cats could be classified according to whether they were "low", "intermediate" or "high" IgG responders, by quantification of serum IgG values. Cats with the lowest serum IgG values failed to develop glomerulonephritis. However, there was no relationship between actual IgG values and the severity of the induced disease. In contrast to IgG, there was no division of cats into low or high IgM anti-HSA responders. Again, cats with the lowest IgM values failed to develop GN, but, more interestingly, a late, marked increase in serum IgM anti-HSA occurred only in cats that developed clinical signs of GN (anterior uveitis and nephrotic syndrome). Maturation of average, functional IgG affinity (avidity) for HSA following chronic immunization was clearly demonstrated for all cats. At the end of the experiment, all cats had IgG of high affinity for HSA and the average affinity heterogeneity of the IgG populations was less than in measurements taken earlier. Values of IgG affinity at the end of the experiment were very similar both in cats which developed GN and in those which remained clinically, biochemically and pathologically normal. In contrast to IgG antibody, some cats developed IgM of increased affinity, whilst others produced antibody of reduced affinity, following chronic immunization. There was no correlation between the development of disease and the production of either low or high affinity IgM antibody. Data indicated that an alteration in IgM affinity occurred at a late stage, as serum IgM levels increased, in cats which progressed to develop GN. These findings suggested that an increase in both serum IgG and IgM anti-HSA values, in particular IgM, was associated with the development of a more severe immune complex renal disease in these cats. Although there was no evidence that differences in the average affinity of either the IgG or IgM antibody populations for HSA, were associated with the development of disease, the increase in IgM values was also accompanied by a concomitant alteration in IgM affinity for antigen.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1430351 TI - Soft tissue reconstruction with skin grafting. AB - Free skin grafts for soft tissue reconstruction can be classified into three types: full-thickness skin grafts, split-thickness skin grafts, and composite grafts. The indications, techniques, donor site considerations, and postoperative complications of each type of skin graft are reviewed. PMID- 1430352 TI - Expression of adhesion proteins involved in cell-cell and cell-matrix interactions in the skin of patients with progressive systemic sclerosis. AB - BACKGROUND: Lymphocytic infiltration and activation of connective tissue metabolism in the early phase of progressive systemic sclerosis (PSS, scleroderma) may be critically influenced by cellular adhesion molecules (CAMs), which mediate cell-cell and cell-extracellular matrix interactions. OBJECTIVE: The tissue distribution might demonstrate a pathogenetic role of these adhesion molecules in early edematous and chronic fibrotic scleroderma. METHODS: We investigated by immunohistochemical techniques the in situ expression and distribution of beta 1 and beta 2 integrins, selectins, and CAMs of the immunoglobulin superfamily in patients with scleroderma. RESULTS: In the early disease stage a moderate percentage of perivascular CD3+/CD4+/TCR alpha/beta + lymphocytes showed expression of the alpha 3, alpha 5, and beta 1 chains and, to a lesser degree, of the alpha 1, alpha 2, alpha 4 and alpha 6 subunits. In contrast to chronic PSS, LFA-1 alpha, LFA-1 beta and ICAM-1 expression on mononuclear infiltrating cells was seen more frequently in acute scleroderma. Different percentages of fibroblasts expressed alpha 1-, alpha 3-, alpha 5- and beta 1-integrin chains. In acute PSS ICAM-1 was expressed especially by fibroblasts located around perivascular inflammatory infiltrates as well as by endothelial cells (ECs). A few ECs expressed alpha 2 beta 1 integrins. CONCLUSION: Our observations suggest that CAMs are intimately involved in early pathogenetic events in scleroderma, mediating cellular interactions between lymphocytes, ECs, and fibroblasts, as well as homing and tissue targeting of mononuclear infiltrating cells. PMID- 1430353 TI - Serum androgens and depression in women with facial hirsutism. AB - BACKGROUND: Studies on the psychopathologic aspects of hirsutism are sparse. Attempts to correlate these aspects with either the extent of the facial hirsutism and/or circulating serum androgens are virtually nonexistent. This study evaluates the psychopathologic aspects of hirsutism and correlates these findings with the extent of the facial hirsutism as well as with the circulating serum androgens. OBJECTIVE: Our purpose was to assess the psychopathologic aspects of facial hirsutism and to determine whether any correlation exists between these findings and either the extent of the facial hirsutism or the circulating serum androgens. METHODS: Twenty consecutive women with facial hirsutism were studied by administration of psychologic tests (DeRogatis Symptom Inventory and the Affects Balance Scale). The results of these tests were correlated with the grade of facial hirsutism as well as serum levels of total testosterone (T), biologically active testosterone (BT), free testosterone (FT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione (A-dione). RESULTS: Significant levels of depression were found. No correlation was found between the psychopathologic measurements and the extent of facial hirsutism or serum levels of T, DHEA, DHEA-S, and A-dione. Significant correlations were found between depression and serum levels of FT and BT. CONCLUSION: There is an increased incidence of depression in facially hirsute women and this correlates with their circulating active testosterone levels and not with the extent of their facial hirsutism. PMID- 1430354 TI - Effectiveness of various barrier preparations in preventing and/or ameliorating experimentally produced Toxicodendron dermatitis. AB - BACKGROUND: Despite extensive research on hyposensitization and prior application of topical barrier preparations, efforts to prevent Toxicodendron dermatitis have been only minimally successful. OBJECTIVE: Seven different barrier creams were evaluated for topical protection against experimentally produced Toxicodendron dermatitis in a randomized, double-blind study. METHODS: Twenty patients had the seven barrier creams randomly applied to eight test sites (one untreated area as control) on each forearm before application of the Toxicodendron extract. Development of Toxicodendron dermatitis was followed for 8 days, with measurements of erythema, induration, vesiculation, and global severity taken at each site on days 1, 2, 3, 4, and 7 after Toxicodendron application. RESULTS: The barrier creams Stokogard, Hollister Moisture Barrier, and Hydropel significantly reduced the erythema, induration, and global severity of Toxicodendron dermatitis and did not differ from each other. The percent reductions in global dermatitis severity per day of assessment for the seven barriers in order of effectiveness were as follows: Stokogard, 59%; Hollister Moisture Barrier, 52%; Hydropel, 48%; Ivy Shield, 22%; Shield Skin, 13%; Dermofilm, 13%; and Uniderm, -9%. During the 8 day period, a significantly greater number of test sites pretreated with Stokogard, Hollister Moisture Barrier, and Hydropel were free of dermatitis compared with control sites and sites treated with the other four barriers. CONCLUSION: The results indicate that Stokogard, Hollister Moisture Barrier, and Hydropel are effective in the prevention of Toxicodendron dermatitis. PMID- 1430355 TI - A characteristic cutaneous direct immunofluorescent pattern associated with Ro(SS A) antibodies in subacute cutaneous lupus erythematosus. AB - BACKGROUND: Antibodies to Ro(SS-A) are present in most patients with subacute cutaneous lupus erythematosus (SCLE). Patients with SCLE also have cutaneous immune deposits. However, no correlation of Ro(SS-A) antibodies with immune deposits in skin biopsy specimens has been described. OBJECTIVE: The purpose of this study is to describe characteristic direct immunofluorescence (IF) findings in 32 patients and their association with serum antibodies and clinical diagnosis. METHODS: Serum from patients with characteristic cutaneous direct IF findings was examined for antinuclear antibodies by indirect IF and for antibodies to ribonucleoprotein, Sm, Ro(SS-A), and La(SS-B) by gel immunodiffusion. RESULTS: Twenty-two of 32 patients who exhibited discrete speckled IgG staining predominantly, but not exclusively, of the basal cell cytoplasm had SCLE. Ro(SS-A) antibodies were identified in 23 of 26 patients and Ro(SS-A) and/or La(SS-B) in 25 of 26 patients. CONCLUSION: Direct IF staining characterized by discrete speckled IgG deposits in the basal cell cytoplasm is associated with Ro(SS-A) antibodies and SCLE. PMID- 1430356 TI - North Carolina tanning operators: hazard on the horizon? AB - BACKGROUND: Previous small studies have demonstrated that operators of commercial tanning equipment may not be adequately trained. Most states have no training requirements for tanning operators. This study was designed to assess the medically relevant knowledge of cosmetic tanning salon operators and relate these to demographic variables. METHODS: A written, anonymous questionnaire was distributed to 984 attendees of the first required operator training seminars conducted in North Carolina. Between July 1990 and June 1991, proprietors and their employees of the commercial tanning industry who attended these seminars were surveyed. No conference attendee refused to complete the questionnaire. Demographic information and responses to the medical information section of the questionnaire were scored by computer. RESULTS: Important findings included that 71% of surveyed operators had never received any training for their current position. Operators of cosmetic tanning equipment were often unaware of contraindications to tanning such as photosensitizing drugs and specific medical conditions. Few operators recognized methoxsalen (26%) or trisoralen (34%) or their respective proprietary names as contraindications to tanning. Operator knowledge was not related to their educational achievement, previous tanning salon experience, or prior tanning industry-sponsored training. Children younger than 10 years old were tanned by 2.6% of the operators. CONCLUSION: These data suggest that the public may be at risk for UV light-induced diseases and burns because of operator lack of knowledge. PMID- 1430357 TI - Photosensitivity induced by fibric acid derivatives and its relation to photocontact dermatitis to ketoprofen. AB - BACKGROUND: Photosensitivity reactions to fibric acid derivatives are not well understood and have been rarely reported. OBJECTIVE: The aim of this study was to describe two cases of photosensitivity, one induced by fenofibrate and one by bezafibrate; to study the in vivo photosensitizing potential of these drugs; and to evaluate the possibility of cross-reactivity between fenofibrate and ketoprofen. METHODS: Patch and photopatch tests with fibric acid derivatives and ketoprofen were performed in the patients, in 12 normal volunteers, and in 7 patients with photopatch-proven photocontact dermatitis to ketoprofen. Phototesting studies were performed both while the patients were taking the drugs and after withdrawal of them, as well as in a group of 18 hyperlipemic volunteers without history of photosensitivity who were taking therapeutic doses of fenofibrate or bezafibrate for 2 to 3 months. RESULTS: Positive photopatch test responses to ketoprofen and to fenofibrate were obtained only in the first patient, who also had a weaker positive ordinary patch test response to the latter. Five patients photosensitized to ketoprofen also had a positive patch test to fenofibrate. Phototesting studies were abnormal in both patients but normal in all volunteers. CONCLUSION: An association between systemic photosensitivity to fenofibrate and photocontact sensitivity to ketoprofen seems to exist. The structural similarities of these chemicals favor cross-reactivity. PMID- 1430358 TI - The site of blister formation in dermatitis herpetiformis is within the lamina lucida. AB - BACKGROUND: Because the initial neutrophilic infiltrate in dermatitis herpetiformis is within the dermal papillae, most investigators have assumed the vesicles occur in this same area. This was supported by electron microscopy studies. In 1983 Klein et al. refuted this concept, suggesting that vesicle formation was within the lamina lucida above the lamina densa. Despite this study, current literature continues to state that blister formation is below the lamina densa. OBJECTIVE: Our purpose was to determine the ultrastructural site of blister formation in early and late vesicles of dermatitis herpetiformis. METHODS: We evaluated eight biopsy specimens from four patients by immunomapping with antibodies to bullous pemphigoid antigen, laminin, type IV collagen, and epidermolysis bullosa acquisita antigen. RESULTS: In both early and late vesicles blister formation was found to be above the lamina densa in the lamina lucida. CONCLUSION: These findings are contrary to the commonly held concept that the blister in dermatitis herpetiformis is below the lamina densa and confirm the findings of Klein et al. that the site of blister formation in dermatitis herpetiformis is above the lamina densa within the lamina lucida. PMID- 1430359 TI - Verification of a formula for determination of preexcision surgical margins from fixed-tissue melanoma specimens. AB - BACKGROUND: Recently our group reported on the shrinkage of 199 malignant melanoma surgical-excision specimens. In that report, a multivariate analysis revealed that the age of the patient was the only factor that significantly affected the percentage shrinkage of a surgical specimen. In addition, a formula was presented that extrapolates the actual surgical margins (in vivo) from the (contracted) fixed-tissue pathology report measurement and the reported in vivo lesion diameter. OBJECTIVE: The goals of this study are to verify that shrinkage of surgical specimens is approximately 20% and that the margin formula can be successfully applied to a different group of patients. METHODS: Four hundred seven patients with malignant melanoma were prospectively enrolled to measure preexcision (outlined with ink) surgical margins, fixed-tissue (contracted) surgical margins, and overall specimen shrinkage. RESULTS: It is verified that overall shrinkage of cutaneous surgical specimens is approximately 20%. Surgical specimens from patients younger than 50 years of age have approximately 25% shrinkage. Those specimens from patients 50 to 59 years of age have approximately 20% shrinkage and those from patients 60 years of age or older have about 15% shrinkage. The surgical margins predicted by the margin formula were within +/- 3.5 mm of the actual measured surgical margin 86.5% of the time. CONCLUSION: The actual surgical margins (in vivo) of a malignant melanoma can be reasonably estimated from the fixed-tissue pathology measurement via the margin formula. The shrinkage of a surgical specimen is 15% to 25% depending on the patient's age. PMID- 1430360 TI - Treatment of telangiectases and other benign vascular lesions with the 577 nm pulsed dye laser. AB - BACKGROUND: This study was undertaken to evaluate the effectiveness and safety of the 577 nm pulsed dye laser in the treatment of various vascular lesions of the face. OBJECTIVE: Our purpose was to make observations on the effects of different variables that could affect response. METHODS: Ninety-two adults with telangiectases of the face were sequentially selected for treatment according to a protocol previously established. Evaluation consisted of visual inspection by two investigators, and before and after photographs at 2-months intervals. A few patients with other vascular lesions were also treated and reported. RESULTS: Ninety-one percent of the patients (84 of 92) showed good to excellent response after a single treatment. Recurrence occurred in 2%. Atrophy of the skin occurred in 2%. Venous lakes, pyogenic granulomas, and mucosal vascular malformations showed significant improvement. CONCLUSION: The 577 nm pulsed dye laser is effective and safe for vascular lesions of the face. PMID- 1430361 TI - Topical treatment of Old World cutaneous leishmaniasis caused by Leishmania major: a double-blind control study. AB - BACKGROUND: A controlled study of the efficacy of topical paromomycin sulfate (PR) and methylbenzethonium chloride (MBCl) in cutaneous leishmaniasis (CL) has not yet been performed. OBJECTIVE: The therapeutic effect of an ointment containing 15% PR and either 12% or 5% MBCl (15/12 or 15/5 P-ointment) on patients suffering from Old World CL was examined in a randomized, double-blind, cross-over study. METHODS: Thirty-nine patients with Old World CL caused by Leishmania major were treated topically, twice daily, for 10 to 20 days with 15/12 or 15/5 P-ointment and 10 to 20 days with a placebo ointment to achieve a total of 30 days of treatment in all groups. RESULTS: In the P-ointment-treated groups, 74.2% (29 of 39 patients) of the patients were cured versus 26.6% (4 of 15 patients) in the placebo-treated group. Little difference was found between the 15/12 and 15/5 P-ointment groups. CONCLUSION: In most of the patients treated with the active ingredients, total elimination of the parasites was achieved within the first 10 days of treatment. PMID- 1430362 TI - Immunohistochemical examination of lichen nitidus suggests that it is not a localized papular variant of lichen planus. AB - BACKGROUND: Lichen nitidus is believed, by some, to be a variant of lichen planus, and by others to be a distinct entity. OBJECTIVE: We examined five cases of lichen nitidus with immunohistochemical reagents designed to characterize the dermal inflammatory infiltrate in an attempt to resolve the uncertainty. METHODS: We stained formalin-fixed, paraffin-embedded tissue sections with the following antibodies: L26, A6, KP1, BerH2, OPD4, and HECA-452. RESULTS: The inflammatory infiltrate was 90% A6+, with few L26+ cells. In contrast to lichen planus, KP1+ macrophages were seen and fewer of the lymphocytes demonstrated HECA-452. Fifty percent to 80% of lymphocytes were OPD4 positive, similar to that usually seen in lichen planus. Rare Ki-1+ cells were seen in one case. CONCLUSION: We believe that the pattern of a mixed cellular infiltrate characterized by macrophages and a helper T cell response with few HECA-452+ cells is somewhat different from the pattern seen in lichen planus, wherein almost all of the cells are CD4+/HECA-452+ lymphocytes. This suggests a different immunologic pathogenesis. PMID- 1430363 TI - Basaloid follicular hamartoma: solitary and multiple types. AB - BACKGROUND: Multiple skin tumors often show autosomal dominant inheritance; solitary neoplasms are typically nonhereditary. OBJECTIVE: The purpose of this study was to investigate a possible hereditary pattern in patients with multiple and solitary basaloid follicular hamartomas. METHODS: Four new familial cases of multiple basaloid follicular hamartomas and 56 solitary nonhereditary examples were identified and their inheritance pattern recorded. RESULTS: Clinically, basaloid follicular hamartomas were typically 1 to 2 mm, smooth facial papules. Histologically, they were well-circumscribed lesions composed of anastomosing strands of squamoid and basaloid cells in a loose stroma. Horn cysts and pigmentation were common. No significant association with other cutaneous or internal disease was found. CONCLUSION: Basaloid follicular hamartoma, a unique benign follicular tumor, was often diagnosed previously as trichoepithelioma or basal cell carcinoma. It is another cutaneous neoplasm in which patients with multiple lesions show autosomal dominant inheritance, whereas solitary growths with identical clinical, microscopic, and biologic features are nonhereditary. PMID- 1430365 TI - Oral hairy leukoplakia unassociated with human immunodeficiency virus: pseudo oral hairy leukoplakia. PMID- 1430364 TI - Surgical margins for excision of primary cutaneous squamous cell carcinoma. AB - BACKGROUND: No guidelines for the margin of resection of cutaneous squamous cell carcinoma have been based on data measuring subclinical tumor extension, as have been formulated for basal cell carcinoma. OBJECTIVE AND METHODS: Guidelines for appropriate margins of excision of primary cutaneous squamous cell carcinoma were formulated on the basis of a prospective study of subclinical microscopic tumor extension. RESULTS: Four millimeter margins were adequate for most squamous cell carcinomas. However, certain tumor characteristics were associated with a greater risk of subclinical tumor extension and included size of 2 cm or larger, histologic grade 2 or higher, invasion of the subcutaneous tissue, and location in high-risk areas. CONCLUSION: Minimal margins of excision of 4 mm around the clinical borders of the squamous cell carcinoma are proposed for all but the high risk tumors, in which at least a 6 mm margin is recommended. PMID- 1430366 TI - Woolly hair nevus syndrome. PMID- 1430367 TI - Pityriasis rubra pilaris in a patient with human immunodeficiency virus infection. PMID- 1430368 TI - Annually recurring acroerythema and hereditary lactate dehydrogenase M-subunit deficiency. PMID- 1430369 TI - Kaposi's varicelliform eruption in a patient with pityriasis rubra pilaris. PMID- 1430370 TI - Human infestation with Cochliomyia hominivorax, the New World screwworm. PMID- 1430371 TI - Rapidly progressive penile ulcer: an unusual manifestation of Kaposi's sarcoma. PMID- 1430372 TI - Coma blisters in a patient with diabetic ketoacidosis. PMID- 1430373 TI - Malignancy-associated tripe palms. PMID- 1430374 TI - Kaposi's sarcoma occurring de novo in the surgical scar in a heart transplant recipient. PMID- 1430375 TI - Pyoderma gangrenosum in infancy. PMID- 1430376 TI - Annular erythema associated with Sjogren's syndrome. PMID- 1430377 TI - Follicular thyroid carcinoma metastatic to the skin. PMID- 1430378 TI - Essential thrombocythemia and idiopathic cold agglutinin disease: two additional disorders associated with intravascular coagulation necrosis of the skin. PMID- 1430379 TI - Melanocytic nevus density in Asian, Indo-Pakistani, and white children. PMID- 1430380 TI - Bullous pemphigoid and severe erythrodermic psoriasis: combined low-dose treatment with cyclosporine and systemic steroids. PMID- 1430381 TI - Systemic therapy with cyclosporine. PMID- 1430382 TI - Sebaceous carcinomas of the ocular adnexa and the Muir-Torre syndrome. PMID- 1430383 TI - Thinning of the ozone layer: facts and consequences. AB - The ozone layer is showing small but definite signs of depletion. Despite this, significantly increased UV radiation transmission at ground level has been found only in the Antarctic and Arctic regions. The potential for increased transmission of UV radiation will exist for the next several hundred years. Although little damage from increased UV radiation has occurred so far, the potential for long-term problems is great. The natural history of ozone and the causes and consequences of, and possible solutions to ozone depletion are examined in this article. PMID- 1430384 TI - Psoriasis and human immunodeficiency virus infection. AB - BACKGROUND: Psoriasis associated with human immunodeficiency virus (HIV) infection has been reported to be severe and perhaps associated with decreased survival. OBJECTIVE: Our purpose was to document the natural history, response to therapy, and effect of psoriasis and its treatment on survival in HIV-infected patients with psoriasis. METHODS: This was an observational cohort study of 50 persons with psoriasis and HIV infection followed up during a 2-year period. RESULTS: In one third of the patients the psoriasis appeared before 1978, the year when HIV seroconversion began in San Francisco (group I). In two thirds psoriasis developed after 1978 (group II). Group I had a lower mean age of onset (19 vs 36 years) and more commonly had a family history of psoriasis. Palmoplantar and inverse psoriasis were more common in group II. Severe psoriasis occurred in one fourth of this group (12 of 50 patients). The median survival in this group after diagnosis of acquired immunodeficiency syndrome (AIDS) was 19 months, which is comparable to the median survival for all AIDS patients diagnosed in San Francisco between 1984 and 1990. CONCLUSION: Psoriasis in the setting of HIV disease may be mild, moderate, or severe. Standard therapies and zidovudine are effective in management. Survival does not seem to be adversely affected by the presence of psoriasis or its therapy. PMID- 1430385 TI - Differences in direct immunofluorescence staining patterns in epidermolysis bullosa acquisita and bullous pemphigoid. AB - BACKGROUND: Both bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA) are characterized by linear IgG deposits along the basement membrane zone (BMZ). Although these diseases can be distinguished by special tests, the staining pattern on direct immunofluorescence (DIF) is identical. OBJECTIVE: The purpose of the present study was to reevaluate DIF as a diagnostic tool in differentiating EBA from BP. METHODS: We performed DIF studies on biopsy specimens from eight consecutive patients with EBA and 18 consecutive patients with BP. RESULTS: In five of eight cases of EBA, C3 deposition was essentially absent. IgG was the predominant class of immunoglobulins in the deposits and was present along the BMZ in all eight cases. C3 was present in 17 of 18 cases of BP. IgG was the predominant immunoglobulin present in 15 of these 18. CONCLUSION: Patients with EBA are more likely to have linear IgG staining along the BMZ without concomitant C3 deposition than are patients with BP. This difference may be a function of the ability of the autoantibodies to fix complement. PMID- 1430386 TI - Small-diameter malignant melanoma: a common diagnosis in New South Wales, Australia. AB - BACKGROUND: The "ABCDE" guide developed at the New York University Medical Center and Harvard Medical School has proved useful in the detection of early malignant melanomas. This guide stipulates that melanomas usually are more than 6 mm in maximal diameter and are elevated. OBJECTIVE: Our purpose was to determine whether these size criteria applied in Australia. METHODS: The records of 1150 melanoma patients at the Sydney Melanoma Unit between June 1989 and September 1991 were reviewed. RESULTS: Almost one third of the 1150 melanomas (358) were 6 mm or less in maximal diameter, and the median thickness of these 358 melanomas was 0.8 mm. CONCLUSION: The "ABCDE" guide to the signs of early melanoma may have to be modified to include smaller diameter, clinically impalpable melanomas. There appears to be a close correlation between patient age at diagnosis and both lesion diameter and thickness. Because increases in diameter occurred more rapidly than increases in thickness, subtle increases in lesion diameter may provide a better clue to earlier diagnosis. PMID- 1430387 TI - Hydrocortisone sensitivity: clinical features of fifty-nine cases. AB - BACKGROUND: Hypersensitivity to topical steroids is becoming increasingly recognized. OBJECTIVE: Our purpose was to establish factors associated with allergy to topical hydrocortisone. METHODS: Data from 59 consecutive patients allergic to hydrocortisone were compared with 199 consecutive patients who were not allergic to hydrocortisone. RESULTS: Patients with stasis dermatitis and leg ulceration were significantly more likely to be allergic to hydrocortisone. In patients with hand eczema, in whom hydrocortisone sensitivity was less common, hydrocortisone was still a common allergen, occurring as frequently as wool alcohols and colophony. In four patients with atopic eczema, hydrocortisone was the only allergen. Duration of dermatitis was not important in determining the presence of hydrocortisone allergy. However, patients allergic to hydrocortisone were more likely to have multiple allergies when compared with control subjects. CONCLUSION: Allergy to topical hydrocortisone is associated with stasis dermatitis and multiple positive patch test reactions. PMID- 1430388 TI - Perioral dermatitis in childhood. AB - BACKGROUND: Although perioral dermatitis has been well described in young women, little has been reported about this condition in children. OBJECTIVE: The purpose of this study was to define more clearly the features of perioral dermatitis in childhood. METHODS: Fourteen children with perioral dermatitis were assessed for clinical features, therapeutic response, and possible etiologic factors. RESULTS: Fourteen cases of perioral dermatitis were seen in 16 months, far exceeding the expected prevalence in childhood. Although the childhood variant shares many characteristics with the adult form, children often have periocular and perinasal lesions, as well as a higher relative incidence in boys. Mid- to high-potency topical corticosteroids were used in seven of the patients (50%) and likely contributed to the pathogenesis. All children responded rapidly to treatment. CONCLUSION: Perioral dermatitis in childhood, often iatrogenic, is more common than previously reported. PMID- 1430390 TI - Pigmented Spitz nevi: improvement of the diagnostic accuracy by epiluminescence microscopy. AB - BACKGROUND: Pigmented Spitz nevi have distinct clinical features but often may be difficult to differentiate from malignant melanoma by clinical criteria. OBJECTIVE: The purpose of this study was to use a new noninvasive diagnostic approach to improve the clinical diagnosis of Spitz nevi. METHODS: Epiluminescence microscopy (ELM) is a new, noninvasive technique for which criteria for the diagnosis of melanocytic tumors, benign and malignant, recently have been established. These criteria were tested in an investigation of 54 pigmented Spitz nevi. RESULTS: With ELM the accuracy of clinical diagnosis of pigmented Spitz nevi improved from 56% (clinical) to 93% (ELM). CONCLUSION: Our findings suggest that ELM criteria are useful to improve the accuracy of clinical diagnosis of Spitz nevi. PMID- 1430389 TI - Unilateral laterothoracic exanthem in children: a new disease? AB - BACKGROUND: We have examined 18 children with a similar laterothoracic exanthem that appears to represent a distinct entity. OBJECTIVE: Our purpose was to describe the characteristic signs and clinical course of this eruption and its epidemiology data. METHODS: We observed the clinical course of the eruption in each child. RESULTS: The eruption has characteristic features. It occurs in a homogeneous age group (mean 23.3 months). It is initially unilateral and localized close to the axilla. The basic lesion is eczematous or scarlatiniform. The eruption evolves in two phases: it spreads centrifugally during the first 8 days and becomes more widespread on the tenth to fifteenth days, with predominant involvement on the half of the body initially affected. The lesions resolve spontaneously within 4 weeks. The long-term course is uneventful. CONCLUSION: The similarity of the cases suggests the existence of a new clinical entity. Many features favor a viral origin. PMID- 1430391 TI - Atypical melanocytic nevi. Clinical and histopathologic predictors of residual tumor at reexcision. AB - BACKGROUND: The appropriate method for surgical management of melanocytic lesions with disordered architecture and melanocytic atypia (formerly dysplastic nevi) has been controversial. Physicians often reexcise these lesions after primary removal because of their potential relation to malignant melanoma. The outcomes of these reexcisions and the original biopsy specimens have not been previously examined. OBJECTIVE: The purpose of this study was to examine reexcision specimens and their respective original specimens to determine whether there were any characteristics predictive of the presence of residual nevus cells (RNCs) on reexcision. METHODS: One hundred eighty-nine reexcision specimens of atypical melanocytic lesions were evaluated for this study. The original specimens were examined for specific histopathologic features without knowledge of the findings on reexcision. Clinical characteristics were also examined. RESULTS: Of the 189 reexcision specimens, 47 (24.9%) contained RNCs. The proportion of specimens with RNC on reexcision was significantly greater if the original lesion was removed by punch biopsy rather than by shave or elliptical excision (38.3% vs 22.0% vs 10.5%, respectively; p < 0.03). Lesions located on the chest had a higher likelihood of RNCs than those on the back or leg (52.2% vs 21.7%; p = 0.009; 52.2% vs 9.7%, p < 0.002, respectively). Mean age was greater in those with RNCs at reexcision than those without (43.6 vs 37.9 years, respectively; p < 0.0001). The proportion of specimens with RNCs at reexcision was greater in those that had both lateral margins involved than in those that had nevus cells in either one or neither of the lateral margins in the original biopsy specimens (39.7% vs 24.0% vs 7.8%, respectively; p = 0.0005). One of the 189 reexcision specimens (0.5%) contained melanoma, although the original histopathologic diagnosis was an atypical melanocytic nevus. CONCLUSION: We identified several clinical and histopathologic factors that are strongly associated with the presence of RNCs on reexcision. PMID- 1430392 TI - Role of foods in the pathogenesis of chronic paronychia. AB - BACKGROUND: Chronic paronychia is a condition that is pathologically characterized by spongiotic inflammation; it can be exacerbated by various and concomitant factors. OBJECTIVE: The aim of this study was to assess whether chronic paronychia in food handlers may have clinical, pathologic, and immunohistochemical similarities with immediate contact dermatitis caused by foods. METHODS: Twenty food handlers affected by chronic paronychia were submitted to patch tests with the fresh foods that were suspected of being the cause of the dermatitis. RESULTS: Nine patients had a positive reaction to a 20 minute open patch test with fresh foods applied on the proximal nailfold. In two patients the pathologic study of the positive open patch test site showed acanthosis, exocytosis, and spongiosis of the epidermis and the presence of an inflammatory lymphocytic infiltrate in the dermis. CONCLUSION: Our results confirm the view that an immediate hypersensitivity reaction to foods can be responsible for some cases of chronic paronychia in food handlers. PMID- 1430393 TI - Malignant tumors in patients with psoriasis. AB - BACKGROUND: There is strong epidemiologic evidence that psoriasis treatments may cause nonmelanoma skin cancer and possibly other types of cancer. OBJECTIVE: This study from Denmark reports the cancer incidence in 6910 patients with psoriasis discharged from the hospital from 1977 through 1987. METHODS: Patients were identified in the National Hospital Discharge Register and information on cases of cancer was obtained through the files of the Danish Cancer Registry; observed figures were compared with those expected on the basis of cancer incidence rates for the national population. RESULTS: A 2.5-fold increased risk was observed for nonmelanoma skin cancer in men and women, with no preponderance of any specific histologic subtype of cancer. In addition, excesses were seen of lung cancer in men (relative risk [RR] = 1.4) and women (RR = 1.6), of cancer of the larynx and pharynx in men (RR = 2.8 and 3.9), and of colon and kidney cancer in women (RR = 1.6 and 2.3). CONCLUSION: The effect of cigarette smoking on the risk for noncutaneous cancer could not be assessed in this study; however, antipsoriatic treatment such as ionizing radiation and oral arsenicals must be considered as a possible cause of colon cancer, which has been observed in excess in two other studies of psoriatic patients. PMID- 1430394 TI - The effect of intralesional 5-fluorouracil therapeutic implant (MPI 5003) for treatment of basal cell carcinoma. AB - BACKGROUND: Basal cell carcinomas (BCCs) are usually treated with ablative procedures. A nonsurgical treatment alternative would be of value in selected patients. OBJECTIVE: We evaluated the safety and efficacy of a new preparation for intralesional sustained-release chemotherapy with MPI 5003, 5-Fluorouracil Therapeutic Implant, for treatment of BCCs. METHODS: Two doses of intralesional MPI 5003 (0.25 and 0.5 ml) were compared in a double-blind study of 20 patients with biopsy-proven BCC. One BCC per patient was treated weekly for up to 6 weeks and followed up monthly for 3 months until excisional biopsy for histologic examination. Before excision the cosmetic appearance of the test site was graded. RESULTS: Eighty percent of 10 BCCs treated with 0.5 ml of MPI 5003 had histologically confirmed cures as compared with 60% of 10 tumors treated with the lower dose (0.25 ml). Cosmetic assessments before excision were typically good to excellent. No systemic side effects occurred. CONCLUSION: Results indicate the potential of MPI 5003 for targeted local chemotherapy for BCC. PMID- 1430395 TI - Extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma. AB - BACKGROUND: Many regimens are used for cutaneous T-cell lymphoma (CTCL), but with advanced disease response rates and patient survival are not adequate with any current therapy. Recently extracorporeal photochemotherapy (ECP) was proposed as an alternative therapy. OBJECTIVE: Our purpose is to present the results of ECP in patients with CTCL refractory to other treatments. METHODS: Patients with CTCL received ECP at 3- to 5-week intervals for at least 6 months. All patients except one were in stage T2 (patch/plaque) or higher. Eight patients had extracutaneous disease involving lymph nodes (six patients), bone marrow (five), or Sezary cells (six). The interval between initial symptoms and diagnosis was 5.9 +/- 1.9 years (mean +/- standard error of the mean) and the interval between diagnosis and ECP was 2.2 +/- 0.4 years. RESULTS: A complete response (disappearance of all lesions) was obtained in five patients (25%) and a partial response (disappearance of at least 50% of lesions) in six patients (30%). Four patients (20%) showed stabilization of their disease and five progressed (25%). The only variable that predicted responders versus nonresponders was the number of ECP sessions (p < 0.05 by multivariate logistic regression). In contrast, no separate beneficial effect of adjunctive chemotherapy (p > 0.5) or electron beam therapy (p > 0.1) was found. CONCLUSION: Long-term ECP may be an effective alternative treatment for CTCL refractory to other therapies and is likely to be even more useful when combined with other modalities. PMID- 1430396 TI - Carbon dioxide laser treatment of actinic cheilitis. Clinicohistopathologic correlation to determine the optimal depth of destruction. AB - BACKGROUND: The carbon dioxide laser is an effective modality for the treatment of actinic cheilitis, but the number of passes required is unknown. After each pass different visual tissue qualities are observed. OBJECTIVE: Our purpose was to identify and characterize histologically the tissue zones seen after laser impact and thereby to determine the optimal depth of destruction of diseased tissue. METHODS: Twenty-three biopsy specimens from 14 patients were obtained from zones of different tissue qualities after one and three passes with the laser. Specimens were histologically examined for the presence or absence of diseased epithelium and degree of thermal necrosis. RESULTS: Complete destruction of the epithelial layer was observed in all specimens irrespective of the number of laser passes. The amount of dermal homogenization increased with multiple passes. CONCLUSION: Treatment to the first or second surgical zone is effective for actinic cheilitis. PMID- 1430397 TI - An analysis of interobserver recognition of the histopathologic features of dysplastic nevi from a mixed group of nevomelanocytic lesions. AB - BACKGROUND: The diagnostic criteria for the histopathologic recognition of the dysplastic nevus are defined, but difficult to apply in practice. However, the use of skin biopsy is on the increase to search for this nevus because of a possible role in melanomagenesis. OBJECTIVE: The aim was to determine the degree of observer reproducibility in the detection of histologic nevomelanocytic dysplasia as measured across multiple observers and to test whether each observer was precise over a wide sample population. A second aim was to gain some measure of the threshold a person has for such lesions. METHODS: Histologic specimens from 50 coded nevomelanocytic tumors, which included a group of dysplastic nevi, were independently read by five observers in a blinded fashion. At study completion, the same 50 cases were read again by a melanoma reference pathologist and results analyzed by Cohen's kappa to assess agreement and interobserver variation. RESULTS: Corrected rates of agreement for dysplastic nevi ranged from 0.32 to 0.71. CONCLUSION: Continued study and experience are required for precision and reproducibility in the histologic recognition of dysplastic nevi. PMID- 1430398 TI - Rothmund-Thomson syndrome: review of the world literature. AB - Rothmund-Thomson syndrome is a rare, inherited disorder characterized by poikilodermatous skin changes that appear in infancy. The inheritance is autosomal recessive. Patients exhibit variable features including skeletal abnormalities, juvenile cataracts, and a higher than expected incidence of malignancy. This extensive review of the world literature clarifies aspects of the inheritance, incidence of characteristic features, and malignant potential of this disease. Insight into its origin is provided through a review of the clinical and in vitro studies of endocrine function and possible DNA repair abnormalities. PMID- 1430399 TI - Unilateral dermatomal pigmentary dermatosis: a variant dyschromatosis? PMID- 1430400 TI - Crohn's disease of the vulva. PMID- 1430401 TI - Identical twins with identical alopecia areata. PMID- 1430402 TI - Multiple keratoses and squamous cell carcinoma from cutting oil. PMID- 1430403 TI - Fumaric acid therapy in psoriasis: results and side effects of 2 years of treatment. PMID- 1430404 TI - Traumatic folliculitis of the legs: a persistent case associated with use of a home epilating device. PMID- 1430405 TI - Scurvy: a case in a young healthy woman. PMID- 1430406 TI - Surface microscopy in the diagnosis of micropapular cutaneous metastatic melanoma. PMID- 1430407 TI - Vulvar melanosis and lentiginosis: a case report. PMID- 1430408 TI - PUVA treatment of pigmented purpuric lichenoid dermatitis (Gougerot-Blum) PMID- 1430409 TI - The Rumpel-Leede sign associated with drug-induced erythema multiforme. PMID- 1430410 TI - Ozone depletion: the biologic consequences. PMID- 1430411 TI - Effect of ketoconazole in the hyperandrogenism, insulin resistance and acanthosis nigricans (HAIR-AN) syndrome. PMID- 1430412 TI - Topical mechlorethamine in the treatment of mycosis fungoides. PMID- 1430413 TI - Onset of psoriasis in the tenth decade of life. PMID- 1430414 TI - Severe sun sensitivity and the presence of antinuclear antibodies in patients with polymorphous light eruption-like lesions. PMID- 1430415 TI - Metastatic basal cell carcinoma. PMID- 1430416 TI - Biology of cutaneous squamous cell carcinoma. PMID- 1430417 TI - Mid-dermal elastolysis. PMID- 1430418 TI - Chum salmon (Oncorhynchus keta) stanniocalcin inhibits in vitro intestinal calcium uptake in Atlantic cod (Gadus morhua). AB - Chum salmon (oncorhynchus keta) stanniocalcin was purified, partially identified and tested for bioactivity in an assay on the intestinal calcium uptake in a marine teleost (Gadus morhua). Basic ethanol extraction, ion exchange chromatography, gel filtration and reverse-phase high-performance liquid chromatography resulted in the isolation of a homogeneous glycoprotein that appears as a 46-kDa product under nonreducing conditions and as a 23-kDa product under reducing conditions after sodium dodecylsulphate-polyacrylamide gel electrophoresis. The glycoprotein is likely to be a homodimer composed of two subunits of 23 kDa each. Further characterization indicates homology to Australian eel, sockeye salmon, coho salmon and rainbow trout stanniocalcin, and the glycoprotein is thus concluded to be stanniocalcin. Stanniocalcin-like immunoreactivity was demonstrated in the corpuscles of Stannius of the Atlantic cod, with a specific antiserum raised against purified chum salmon stanniocalcin. The physiological importance and the biological activity of chum salmon stanniocalcin was tested by evaluating its effect on intestinal calcium uptake by the Atlantic cod in vitro. The intestine was perfused, both vascularly and through the intestinal lumen, and the calcium mucosa-to-serosa flux was measured using 45Ca2+ as a tracer. Stanniocalcin decreased the intestinal calcium uptake in a dose-related manner by 13.5% and 22.4% at doses of 2.2 and 10.9 nM stanniocalcin, respectively. The results establish the intestine as a target organ for stanniocalcin in marine teleosts. PMID- 1430419 TI - Sodium-dependent short-circuit current across the yolk sac membrane during embryonic development in normal and shell-less cultured chicks. AB - The transepithelial electrical characteristics of the isolated yolk sac membrane of normal in ovo or shell-less cultured chick embryos were investigated. In normal chicks the potential difference (blood side positive relative to yolk side) and short-circuit current of the membrane increased during development. Ouabain (10(-4) M) on the blood side (basolateral side, serosal side) significantly decreased potential difference and short-circuit current but was without effect on the yolk side (brush border side, mucosal side). Substitution of choline for Na+ in the bathing solutions abolished the potential difference and the short-circuit current; when Na+ replaced choline this effect was reversed. Amiloride added to both sides of the yolk sac membrane had no effect on potential difference or short-circuit current. Injection of aldosterone (50 micrograms) and T3 (10 microM) into yolk did not induce amiloride sensitivity. The short-circuit current was not altered by addition of either glucose or alanine to the bath. The short-circuit current of the yolk sac membrane of shell less cultured embryos was significantly lower than that of normal controls. Addition of Ca2+ to the serosal bathing medium did not reverse the foregoing condition, but decreased the short-circuit current. It is concluded that the yolk sac short-circuit current is Na+ dependent and increases with developmental age in the chick embryo. PMID- 1430420 TI - Seasonal changes in the activation of crossbridge motions of isolated thick filament from Limulus striated muscle. AB - In dynamic light scattering, measurements of the intensity-intensity time correlation function from a suspension of rod-like particles of length L could reveal dynamical information related to translational and internal motions of those particles. For a suspension of thick filaments isolated from the myosin regulated, striated muscles of Limulus at KL greater than 1 (where K is the scattering vector), the average characteristic linewidth (gamma) increased with the addition of Ca2+ or with the depletion of ATP. The increase in the gamma with the addition of Ca2+ could be due to the presence of energy-requiring, high frequency motions of the crossbridges activated by Ca2+. The increase in gamma which occurred with the depletion of ATP was assumed to be mainly due to the thermal motions of the crossbridges after they had moved radially away from the filament backbone. The percentage increase in gamma following the addition of Ca2+ was found to be seasonal, i.e., values of gamma obtained from thick filaments isolated between the middle of June and the middle of September were smaller than those obtained during the rest of the year. The effect of temperature on the percentage increase in gamma was also different. The increase showed a maximum at about 35 degrees C during the summer and at about 25 degrees C at other times. However, the percentage increase in gamma developed under ATP depleted conditions showed no temperature-related maximum. The number of bound Ca2+ per myosin molecule was 1 during the summer and 2 at other times. PMID- 1430421 TI - Effect of steroid hormones on serotonin, norepinephrine and epinephrine contents in the pineal-paraphyseal complex of the soft-shelled turtle (Lissemys punctata punctata). AB - Steroids (testosterone, oestrogen, progesterone, corticosterone, dexamethasone and deoxycorticosterone) were administered intramuscularly (0.1 mg.100 g bw-1) on seven consecutive days to juvenile male soft-shelled turtles. Serotonin, norepinephrine and epinephrine contents of the pineal-paraphyseal complex were measured spectrofluorometrically 24 h after the last injection. Testosterone and oestrogen decreased serotonin, norepinephrine and epinephrine levels. Progesterone treatment resulted in an increase of serotonin level and a fall in norepinephrine and epinephrine levels. Corticosterone treatment caused an increase of serotonin level and a decrease of norepinephrine and epinephrine levels. Dexamethasone failed to alter serotonin content, increased norepinephrine and decreased epinephrine levels. Deoxycorticosterone decreased serotonin and elevated epinephrine content. PMID- 1430422 TI - Relationship between a long-term treatment of 2-mercaptoethanol and protein metabolism in the ageing rat. AB - Female RLEF1/Lati rats were chronically treated with 2-mercaptoethanol in a dose of 13 micrograms.100 g bw-1.day-1 dissolved in drinking water. During a 48-h experiment 15N-labelled glycine was given orally in a dose of 5 mg 15N.kg bw-1 and urine samples were collected and analysed by an emission spectrometric isotope method. Protein synthesis and nitrogen excretion rate constants were calculated according to the three-pool model, and 3-methylhistidine excretion rates were also determined. 2-Mercaptoethanol appears to influence protein metabolism; however, the slower rates of protein synthesis proved to be apparent in almost all groups of treated rats. Protein synthesis and nitrogen excretion rate constants have exceptionally high values in 2-year-old rats, possibly explained by the occurrence of hypercompensation mechanisms in old age. These were reflected by the excretion rates of 3-methylhistidine which were reduced as a result of sulphhydryl group interactions in age-dependent cellular metabolic changes. PMID- 1430423 TI - Digestive tract morphology and digestion in the wombats (Marsupialia: Vombatidae). AB - Wombats consume grasses and sedges which are often highly fibrous. The morphology of the digestive tract and the sequence of digestion were studied in two species of wombats from contrasting habitats: Vombatus ursinus from mesic habitats and Lasiorhinus latifrons from xeric regions. Studies were performed on wild wombats consuming their natural winter diets, and on captive wombats fed a high-fibre pelleted straw diet. Vombatus had a shorter digestive tract (9.2 vs 12.5 times body length) of greater capacity (wet contents 17.9 vs 13.7% body weight) than Lasiorhinus. The most capacious region of the digestive tract was the proximal colon (62-79% of contents). The proportional length and surface area of the proximal colon were greater in Vombatus, but those of the distal colon were greater in Lasiorhinus. These digestive morphologies may reflect adaptations for greater capacity and longer retention of digesta in Vombatus, but greater absorption and lower faecal water loss in Lasiorhinus. Apparent digestion along the digestive tract was estimated by reference to lignin. The proximal colon was the principal site of fibre and dry matter digestion, whereas nitrogen was mainly digested in the small intestine. Depot fats in captive wombats were highly unsaturated and reflected those in the diet. Therefore, lipids, proteins and soluble carbohydrates in the plant cell contents were digested and absorbed in the stomach and small intestine. Conversely, dietary fibre was probably retained and digested by microbial fermentation along the proximal colon. PMID- 1430424 TI - Hindgut fermentation in the wombats: two marsupial grazers. AB - The wombats Vombatus ursinus and Lasiorhinus latifrons have a capacious proximal colon with only a vestigial caecum. The pattern of microbial fermentation in the hindgut of both species was studied in captive animals fed a pelleted straw diet and in wild wombats feeding on their natural winter diets. Digesta pH was low in the stomach but near neutrality along the hindgut, indicating effective absorption and/or buffering of the colonic contents. Initial proportions and production rates of short chain fatty acids in vitro reflected the fermentation of plant cell walls. Proportions of isobutyrate, isovalerate and n-valerate increased towards the distal colon indicating proteolysis and subsequent fermentation of amino acids. The low ammonia content of digesta fluid suggested that ammonia released from these amino acids was absorbed and utilized by the wombats and their gut microbes. Wild wombats had higher concentrations and production rates of short chain fatty acids than captive animals, which was consistent with the higher apparent digestibility of their natural diet. The energy from short chain fatty acids in captive animals was 30-33% of digestible intake. Energy intakes were low and similar to resting metabolic rates estimated for marsupials. Actual resting metabolic rates of the wombats are probably lower than these estimates, and the proportion of energy derived from fermentation substantially higher than the 53-61% estimated in wild wombats. The energy from fermentation clearly enables wombats to utilize diets high in fibre. PMID- 1430425 TI - Intraosseous meningioma: CT and MR appearance. PMID- 1430426 TI - Intraosseous pneumatocyst of the ilium: CT findings. PMID- 1430427 TI - Use of fluid attenuated inversion recovery (FLAIR) pulse sequences in MRI of the brain. AB - Fluid attenuated inversion recovery pulse sequences with a long echo time (TE) have been used to image the brain in one volunteer and four patients. The long inversion time used with this sequence suppresses the signal from CSF and the long TE produces very heavy T2 weighting. The marked reduction in flow artefact from CSF and the high T2 weighting enabled anatomical detail to be seen within the brain stem and produced high lesion contrast in areas close to CSF. Lesions were demonstrated with greater conspicuity than with conventional T2-weighted sequences in patients with cerebral infarction, low grade astrocytoma, and diplegia. PMID- 1430428 TI - Contrast enhanced area of posterior pituitary gland in early dynamic MRI exceeds hyperintense area on T1-weighted images. AB - Seventeen normal pituitary glands were studied by midline sagittal (and in one case axial) dynamic MRI before and immediately after injection of Gd-DTPA, using spin-echo sequences with a short repetition time. Images were obtained at 1 min intervals for 6 min at 1.5 T. A well-defined focal area with marked enhancement was seen in the posterior portion of the pituitary gland on the first image after injection of Gd-DTPA. The size of the early enhancing area in the posterior pituitary (EEPP) was compared with the high signal of the posterior pituitary (HSPP) on the precontrast image. The EEPP was larger than the HSPP in 10 cases (59%). The two were equal in size in seven cases (41%). The EEPP was anteriorly convex in 11 cases (65%), whereas HSPP was anteriorly convex in 4 cases (24%). We believe that EEPP closely represents the real extent of the posterior lobe. Our results support the hypothesis that HSPP may involve only a portion of the posterior pituitary. PMID- 1430429 TI - Intravascular thrombosis as a possible cause of transient cortical brain lesions: CT and MRI. AB - Cortical brain lesions were identified on MRI and CT in 14 patients with a variety of diseases. Each of these patients developed neurologic symptoms, the most prominent of which were seizures, depressed mental status, and blurred vision or cortical blindness. Both the imaging and the neurologic abnormalities resolved spontaneously within a period ranging from 5 to 30 days. Due to location and evolution of the lesions over time we hypothesize that they are secondary to small cortical venous thromboses. PMID- 1430430 TI - Glioependymal cysts: CT and MR findings. AB - Four patients with intracranial glioependymal cysts were evaluated in our institution in the last 7 years. All underwent surgical drainage and biopsy of the cyst wall. Cranial CT revealed a uniformly hypodense lesion with no contrast enhancement in all cases. Magnetic resonance imaging studies revealed a well defined cyst that was isointense to CSF on T1-weighted images and iso- or mildly hyperintense to CSF on proton density and T2-weighted images. In one case, a fluid-fluid level was demonstrated within the cavity, indicating the presence of fluid with a high protein content. A diagnosis of glioependymal cysts can be suggested based on CSF-like intensity patterns on T1-weighted images and iso- or mild hyperintensity on T2-weighted images. PMID- 1430431 TI - Degeneration of the posterior columns of the spinal cord: postmortem MRI and histopathology. AB - Postmortem MR images of two cases of posterior column degeneration were correlated with histopathological findings. The abnormal MR findings were volume loss and high signal intensity of the posterior columns associated with mild deformity of the dorsal surface of the spinal cord, corresponding to tract degeneration on histopathological examination. These results strongly suggest that further development of MR technique will permit in vivo detection of posterior column degeneration. PMID- 1430432 TI - Midline anterior atlas clefts: CT findings. AB - Anterior atlas clefts (AACs) are rare developmental variants that may mimic fractures. Due to the potential severe implications of craniocervical junction trauma, expeditious differentiation between a Jefferson burst fracture and a congenital cleft is essential in trauma patients. Three cases of AAC are presented. Two cases demonstrated incidental AACs; the third case was associated with a Jefferson burst injury. Computed tomography is most helpful in evaluating the integrity of the atlas; however, plain radiography or pluridirectional tomography are best for evaluating displacement of the lateral masses of C1 in relation to C2. PMID- 1430433 TI - The benign fibroosseous lesion: its association with paranasal sinus mucoceles and its MR appearance. AB - Although fibrous dysplasia and ossifying fibroma of the facial bones may, with some difficulty, be distinguishable pathologically, they are inseparable radiographically. Based on a study of 30 patients, there was no good or reliable imaging correlation with the histology and the degree of ossification or the bone(s) involved. Therefore, "benign fibroosseous lesion" has been proposed by several noted bone authorities as the term for these entities. Eleven patients had MRI and the overall signal intensities were low on both T1-weighted and T2 weighted sequences. Areas of high signal intensity on T2-weighted imaging correlated with either cysts within the lesion or the presence of mucocele, especially in the frontoethmoid region. Four such mucoceles are presented. The coexistence of mucoceles and benign fibroosseous lesions may be more common than previously reported. It is both realistic and appropriate for the radiologist to diagnose these entities as benign fibroosseous lesions and leave the final histologic diagnosis to the pathologist who can diagnose most such cases, albeit with some difficulty. Sites of high signal intensity on T2-weighted imaging in the frontoethmoid area should raise the possibility of a coexistent mucocele. PMID- 1430434 TI - Evaluation of soft palate function with MRI: application to the cleft palate patient. AB - Magnetic resonance imaging was employed to evaluate soft palate function in four normal volunteers and four patients with surgically repaired cleft palate, using a GE Signa clinical scanner at 1.5 T and a custom designed receive coil with a sensitivity profile encompassing from the nasopharynx to the larynx. Midsagittal images were obtained using spoiled gradient recalled acquisition at steady state while the subject phonated the following sounds: (a) MMM, (b) SSS, (c) DAH, and (d) EEE. An image at rest with normal breathing was also obtained. The soft palate and its relationship to the airway and the posterior pharyngeal wall were clearly visualized in all cases. Phonation of the prescribed sounds demonstrated the normal range of soft palate motion. The images also depicted the ability of the soft palate to divert airflow to the nasopharynx. Interpretation of functional MRI may be of value in evaluation of surgical results, guidance of speech therapy, and surgical planning in the cleft palate patient. This noninvasive alternative to conventional methods of visualization provides advantages in resolution, repeatability, and patient comfort. PMID- 1430435 TI - Pseudoaneurysms at aortic cannulation site after coronary artery bypass graft: MR findings. AB - Pseudoaneurysm at the aortic cannulation site is a rare but potentially fatal complication of coronary artery bypass surgery. We present two cases in which MRI provided significant information regarding the anatomy and extent of a pseudoaneurysm. In one case both spin-echo imaging and cine MRI with and without gradient moment nulling (flow compensation) were used. The absence of gradient moment nulling in cine MRI provides additional contrast between flowing and static blood. This contrast may complement conventional cine images with gradient moment nulling, providing further information. PMID- 1430437 TI - Anomalous left brachiocephalic vein: CT findings. AB - Eight cases of anomalous position of the left brachiocephalic vein were demonstrated by CT. Six coursed downward lateral to and below the aortic arch to enter the superior vena cava (SVC). Two cases were double left brachiocephalic veins. The superior branch was in the normal position, but the inferior vessel coursed below the aortic arch. Most of these subaortic left brachiocephalic veins enter the SVC at the same level or caudal to the azygous arch. Only two cases were associated with congenital heart disease. This anomalously positioned vessel is asymptomatic but must be distinguished from the pulmonary artery and persistent left SVC, especially when open heart surgery for cardiac malformations is being considered. PMID- 1430436 TI - Airway obstruction by right aortic arch with right-sided patent ductus arteriosus: demonstration by MRI. AB - An unusual cause of airway obstruction was demonstrated by MRI in two infants with congenital heart disease. The two infants experienced airway obstruction caused by a right aortic arch with right-sided patent ductus arteriosus. The diagnosis was established by MRI prior to surgery; angiography did not demonstrate the critical relationship between the large ductus and the airway. Axial, sagittal, and coronal MRI displayed the right arch, dilated ductus, and the compression of the proximal right bronchus and distal trachea by the ductus. Surgical findings confirmed the MR diagnosis. Thus, MRI can be used to localize the site of airway obstruction and to demonstrate unusual types of vascular anomalies. PMID- 1430438 TI - CT evaluation of chronic thromboembolic pulmonary hypertension. AB - Eight patients with chronic thromboembolic pulmonary hypertension (CTPH) that had been demonstrated by perfusion lung scan, pulmonary arteriography, and right heart catheterization had their pulmonary circulation evaluated by CT. Eight subjects without lung pathology were also studied for comparison. High resolution CT from apex to base with 1 cm thick sections after intravenous injection of contrast medium was performed in each individual. Emboli lodged in main pulmonary arteries on arteriography were regularly shown by CT, whereas those in segmental or smaller arteries were not detected. Diameters of the main pulmonary arteries measured on CT correlated with systolic pulmonary artery pressure (p < 0.001). The ratio between diameters of segmental arteries and the corresponding bronchi (A/B ratio) on CT was > 1 in 72 of 144 examined pulmonary segments (18 segments for each patient) in patients with CTPH. The ratio was > 1 in only 10 of 144 examined segments in normal control subjects. Dilatation of bronchial arteries was present in four of eight patients with CTPH. The parenchymal density in patients with CTPH was significantly higher in the axial than in the middle or peripheral lung compartments. In conclusion, CT may help with the diagnosis of CTPH by detecting thrombi of main arteries and by showing characteristic findings; moreover, it is accurate in estimating pulmonary arterial pressure secondary to thromboembolic obstruction. PMID- 1430439 TI - CT findings in "pseudoalveolar" sarcoidosis. AB - To determine the specific high resolution CT (HRCT) features for "pseudoalveolar" sarcoidosis, we reviewed HRCT of 10 patients with pathologically proven sarcoidosis. On HRCT the lesions of pseudoalveolar sarcoidosis were shown as homogeneous or inhomogeneous opacities 1-4 cm in diameter located either along the bronchovascular bundles or in the lung periphery adjacent to the pleural surface. The margin was irregular, and numerous nodules 1-2 mm in diameter were observed in the surrounding lung. Air bronchograms were observed in 6 patients. In addition to these lesions, other CT abnormalities such as nodules, groundglass opacities, thickened bronchovascular bundles, and interlobular septa were found in all 10 cases. Good response of pseudoalveolar sarcoid lesions to administration of corticosteroid was observed in all three cases in which follow up CT was available. PMID- 1430440 TI - Use of nutritional support formula as a gastrointestinal contrast agent for MRI. AB - The objective of this study was to evaluate the potential utility of a nutritional support formula to serve as a practical means of enhancing the gastrointestinal tract on abdominal MR images. Nutritional support formula (Ensure Plus) was administered to 29 patients prior to abdominal MRI. Standard T1 weighted and T2-weighted pulse sequences were performed, in addition to fat suppression and inversion recovery sequences in selected patients. Images in these patients were evaluated for degree and uniformity of gastrointestinal tract enhancement and delineation of the bowel wall and pancreas. Results were compared with those obtained in 10 control patients. Marked enhancement of gastric contents was present in nearly all patients who received nutritional support formula on both T1-weighted and T2-weighted sequences, with mild to moderate enhancement of small bowel and colon in most patients. Although gastrointestinal and respiratory motion artifacts often limited bowel wall delineation, excellent delineation of the gastric wall and pancreas was provided. Phantom experiments demonstrated that gastrointestinal tract enhancement with nutritional support formula is due to the paramagnetic trace elements, corn syrup, and lipid material it contains. Such a formula requires no preparation, is safe, inexpensive, palatable, readily available, and represents a practical means of enhancing the gastrointestinal tract on MRI. PMID- 1430441 TI - CT findings after hepatic chemoembolization. AB - Hepatic arterial chemoembolization (CE) with a mixture of particulate collagen and chemotherapeutic agents was evaluated as therapy for hepatic metastases from colorectal carcinoma. This article describes the characteristics sequential pattern of change seen on liver CT scans following CE. Thirty CT scans were performed on seven patients who had undergone a total of 11 CE procedures. All patients had baseline, immediate postprocedural, and follow-up CT exams at 1 to 2 month intervals following CE. Immediate post-procedural CT scans mapped the area of embolization owing to the density of the contrast mixed with the CE agents. Some lesions seen easily on baseline were more difficult to see as they became isodense with normal liver. Reflux of embolic material into the cystic artery and gallbladder wall was also observed on postprocedural scans in three patients. In all patients, early follow-up scans (1 month after CE) demonstrated changes in lesions seen on baseline scans consistent with tumor necrosis. This was corroborated by a decrease in carcinoembryonic antigen (CEA) levels. In three patients, however, low attenuation regions developed in areas in which there had been no lesion before. The significance of these is uncertain, but the low CEA values and the subsequent evolution in appearance of these sites on CT suggest that they were regions of hepatic ischemia/infarction as opposed to heretofore unidentifiable metastases, now "unmasked." Intermediate follow-up scans (2-3 months) revealed maximal effect on tumor volume, with a decrease of > or = 25% in five of seven patients (71%). Late follow-up scans (> or = 3 months after the last CE) confirmed recurrent disease and new lesions in all cases. PMID- 1430442 TI - Agenesis of the dorsal pancreas with polysplenia syndrome: CT features. PMID- 1430443 TI - Infarction of the kidney: role of contrast enhanced MRI. AB - Magnetic resonance imaging was performed on nine kidneys in six patients with renal infarction caused by renal arterial embolism secondary to cardiac valvular disease. The time interval between the onset of the symptoms attributable to renal infarction and the date of MRI was 2-23 days. On both T1- and T2-weighted images the signal intensity of the infarcted area was lower than that of the noninfarcted area in six kidneys and higher in three kidneys. Postcontrast T1 weighted images demonstrated the extent of the infarction except in the kidney in which the infarcted areas had high signal intensity on precontrast T1-weighted images. PMID- 1430444 TI - MRI of the renal veins: assessment of nonneoplastic venous thrombosis. AB - Nonneoplastic renal vein thrombosis (RVT) is a clinical dilemma that poses a problem both from a clinical and diagnostic imaging perspective. An accurate noninvasive study to diagnose nonneoplastic RVT would be desirable. Magnetic resonance flow imaging is a noninvasive method of assessing vascular patency and depiction of thrombus. Its use for detection of nonneoplastic RVT is reviewed and our experience illustrated. We reviewed retrospectively the MRI studies in 41 patients evaluated for RVT and correlated them with other imaging studies where possible. Twenty patients had either ultrasound or venography. There were no correlative imaging studies done in 21 patients, 19 of whom had normal MRI, with normal clinical follow-up. In others there was good agreement between MRI and ultrasound in 16 of 19 cases. There were five patients with renal venography, of which the MRI agreed with the results in 3 of 5. Magnetic resonance imaging offers a noninvasive approach to the difficult diagnostic dilemma of RVT. PMID- 1430445 TI - CT and MRI of mycotic aneurysms of the abdominal aorta. AB - In two of three patients with mycotic aneurysms of the abdominal aorta, diagnosis was delayed, with a fatal outcome in one patient. A combination of studies, such as indium white blood cell scanning, and anatomical imaging modalities, such as CT and MRI, may be necessary to arrive at the correct diagnosis. PMID- 1430446 TI - Hypointense boundary layer between slow flow and mural thrombus on spin-echo MR. AB - To evaluate the ability of spin-echo MRI to differentiate between slow flow and mural thrombus in aortic diseases, we reviewed the spin-echo MRI of 10 patients with intraaortic thrombus that had been documented by CT in 8 patients and aortography in 2 patients. Six patients had aortic aneurysms with mural thrombi, and four had aortic dissections with adherent mural thrombi within the false lumen. Five of seven gated oblique sagittal or coronal T1-weighted studies demonstrated hyperintense slow flow signal within the residual lumen. This hyperintense slow flow signal was accompanied by a parallel hypointense rim due to a boundary layer dephasing phenomenon. Eight axial T2-weighted MR studies demonstrated a hypointense zone due to fresh clot at the edge of a mural thrombus on even-echo images consistently. The hypointense boundary layer between slow flow and mural thrombus on either gated T1-weighted MRI or second-echo T2 weighted MRI not only predicted the presence of flow within the residual lumen but also clearly separated the area of slow flow from that of mural thrombus in 9 of 10 patients. Proper interpretation of spin-echo images may obviate the need for phase display imaging or gradient-echo imaging in differentiating between slow flow and mural thrombus. PMID- 1430447 TI - Bone marrow edema of the hip: MR findings after core decompression. AB - Magnetic resonance imaging is an extremely sensitive technique for evaluation of bone marrow changes at an early stage of avascular necrosis (AVN) of the hip. We therefore examined 11 painful hips whose clinical symptoms led us to suspect idiopathic AVN. The radiographs of all of these either were normal or demonstrated a minimal decrease in radiodensity. Magnetic resonance demonstrated diffuse signal loss of the bone marrow at short TR/TE images of the femoral head in all hips, with various extensions in the head, neck, and intertrochanteric area. These regions turned iso- to hyperintense on long TR/TE images compatible with bone marrow edema (BME). Focal abnormalities characteristic for AVN were not seen in any of the cases. Radionuclide studies performed in six cases were positive. All patients underwent core decompression treatment. Hydrostatic bone marrow pressure measurement and intraosseous venography were positive in five cases when measured. Histology available in eight cases confirmed the presence of BME. Furthermore, the bone changes corresponded to those of early AVN. Follow-up examinations after core decompression with MR showed normal signal intensity in all cases. Magnetic resonance represents a viable diagnostic tool for BME and can monitor the therapeutic success of core decompression. Whether BME of the femoral head constitutes a distinct transient syndrome or represents an early form of AVN is controversial at present. Our findings support those who believe that BME may represent an initial stage of idiopathic AVN. PMID- 1430448 TI - MR-guided focused ultrasound surgery. AB - Magnetic resonance guided focused ultrasound surgery provides a minimally invasive controlled method for selectively destroying deep-lying tissue. A thermal analysis of focused ultrasound provides an estimate of the time-dependent temperature distribution and thermal dose required for ultrasound surgery. The temperature distribution is estimated by accumulating heat sources, considering the effects of thermal conductivity, heat content, and perfusion. In this study, both gel phantoms and excised in vitro bovine muscle specimens were imaged in a 1.5 T MR system while heated with a 5 cm diameter, 10 cm focal length, 1.1 MHz transducer. During sonication, the thermal effects were observed with T1-weighted pulse sequences. Below a critical temperature, the heat zone appeared as a dark spot that moved with the focal spot. Above a critical thermal dose, the in vitro tissue was irreversibly altered and the focal lesion was observed on both the MR image and the specimen slice. PMID- 1430449 TI - Method for registering brain SPECT and MR images. AB - We have developed a simple method for locating functional regions of interest on successive SPECT scans obtained at different times and for locating neuroanatomical regions defined with MR on functional images obtained with SPECT. Plastic molds are made for each external auditory meatus and the glabella. A pocket is then made in each mold in which either a 57Co disk (for SPECT) or an identical disk containing CuSO4 solution (for MRI) can be placed. Transaxial tomographic slices are reconstructed with the same slice thickness in the two modalities. The SPECT software rotates both SPECT and MRI reconstructed images so that the three 57Co markers lie in one SPECT reference plane and the three CuSO4 markers lie in one MRI reference plane. Corresponding SPECT and MR images may then be displayed simultaneously to locate chosen regions of interest. The technique was validated by taping test markers to the forehead of 12 subjects; the difference between the positions of the centers of the test markers on SPECT and MR scans was within 1 SPECT acquisition pixel size. PMID- 1430450 TI - Diffuse neonatal hemangiomatosis: CT findings in an adult. AB - Diffuse neonatal hemangiomatosis (DNH) is a rare disorder that usually presents in infancy and has a high mortality rate. We report a long-term adult survivor of DNH who presented with multiple calcifications in the bowel wall, liver, spleen, and adrenal glands on CT. Diffuse neonatal hemangiomatosis needs to be added to the causes of visceral calcifications. PMID- 1430451 TI - Primary extraosseous pulmonary osteogenic sarcoma: CT findings. AB - This is a report of a primary extraosseous osteogenic sarcoma of the lung. The patient presented with fever and productive cough. Chest radiography and CT showed a cavitary lesion with an air-fluid level. The lesion was treated as an abscess. Despite aggressive antibiotic therapy and drainage, the patient continued to deteriorate rapidly. At autopsy the lesion was found to be a primary extraosseous pulmonary osteogenic sarcoma. PMID- 1430452 TI - Calcified intrahepatic portal vein thrombus: distinction from intrahepatic choledocholithiasis. AB - In a case of calcified intrahepatic portal vein thrombus CT demonstrated a branching calcified intrahepatic mass with peripheral enhancement following dynamic bolus contrast medium administration. The distinction from intrahepatic choledocholithiasis was made with normal cholangiography. Calcified portal vein thrombus should be considered an unusual cause of branching calcified intrahepatic mass on CT. PMID- 1430453 TI - Inflammatory pseudotumor of the spleen: MR findings. AB - Inflammatory pseudotumor of the spleen is an unusual lesion often mistaken preoperatively for other masses. Isolated inflammatory pseudotumors of the spleen are rare. We report a proven case examined with ultrasound, CT, single photon emission CT, and MRI. PMID- 1430454 TI - Intrapancreatic accessory spleen mimicking pancreatic mass on CT. AB - Accessory spleens occur in approximately 10% of the population and are usually located in the region of the splenic hilum. In 16% of patients the accessory spleen will be located within the pancreatic tail. The diagnosis of an intrapancreatic accessory spleen can be suggested when CT, with and without intravenous contrast agent, demonstrates that the mass enhances in a manner identical to the spleen. PMID- 1430455 TI - Gastroschisis: prenatal CT diagnosis. AB - The prenatal sonographic findings of gastroschisis are well defined. This report describes the CT appearance of fetal gastroschisis discovered as an incidental finding when a 25-year-old pregnant woman underwent CT for blunt abdominal trauma. PMID- 1430456 TI - Amyloid deposition in seminal vesicles mimicking tumor invasion from bladder cancer: MR findings. AB - Amyloid deposition in the seminal vesicle is a not unusual finding at autopsy. A case of MR findings of amyloid deposition in the seminal vesicles with urinary bladder cancer is reported. Invasion of the seminal vesicle could not be excluded on T2-weighted imaging, but gadopentetate dimeglumine may be useful in its ability to differentiate amyloid deposition from seminal vesicle tumor invasion. PMID- 1430457 TI - Gadolinium-enhanced MRI of pigmented villonodular synovitis of the knee. PMID- 1430458 TI - CT and MRI of arachnoid cyst with complicating intracystic and subdural haemorrhage. PMID- 1430459 TI - Cortical and CSF hyperdensity after iodinated contrast medium overdose: CT findings. PMID- 1430460 TI - Program characteristics influencing nurse selection of CE offerings. AB - The purpose of this study was to identify program characteristics that influence decision-making in the selection of continuing education (CE) offerings by registered nurses licensed in a state with mandatory CE. A sample of 238 nurses were asked to identify the level of importance for 35 CE program characteristics on a Likert-like scale. The data indicated that all characteristics were of some importance to participants, with high levels of importance given to items demonstrating professional values. The findings suggest that even though CE may be mandatory, nurses still select educational offerings on the basis of quality and contribution to their professional practice. PMID- 1430461 TI - Nurses and adult educational philosophy: a comparison of nurses and non-nurses in a graduate adult education program. AB - A sample of 90 students enrolled in a graduate program in adult education completed three instruments examining adult education philosophies during a related course. There were no significant differences between the nurse educators and the non-nurses on any of the three instruments or on any of their components. This finding contradicts previous research suggesting that nurse educators do not generally incorporate adult learning methods into their courses. Intercorrelations were computed among all the variables. One unanticipated finding was the significant relationship between age and congruence with adult learning principles. PMID- 1430462 TI - Organizational models and staff preparation: a survey of staff development departments. AB - A national survey of staff development (SD) departments of hospitals was conducted to determine the organizational models (centralized, decentralized, or combination) used. The survey asked about departmental organization, instructor role, staff title, core responsibilities, percentage of work for various departments, SD department head and staff educational preparation, and demographic data. This article discusses the data obtained from the 48 responses (41%) that pertain to the organizational model (26 or 54% used combination model) and staff preparation (master's degree was most prevalent). The data and survey approach could be used by a SD department when choosing an organizational model. PMID- 1430463 TI - Ten common-sense teaching strategies for effective inservice presentation by staff nurses. AB - Staff nurses are currently being given the opportunity to present inservice offerings as a criterion for the professional performance evaluation. Unfortunately, staff nurses, even those with baccalaureate preparation, generally have not been prepared in strategies for effective teaching. Consequently, many staff nurses either avoid this opportunity altogether or may proceed with the "seat of the pants" approach, making learning a chance event. This article sets forth 10 common-sense teaching strategies for effective inservice education presentations with the goal of encouraging and empowering staff nurses to share their particular area of expertise with their peers. PMID- 1430464 TI - A comparison of educational methods to enhance nursing performance in pain assessment. AB - The purpose of this study was to identify an effective method of teaching nurses to assess and document pain severity using a numerical rating scale prior to narcotic administration. Nurses received a combination of educational methods. Although overall nurse performance using the pain scale was low, nurses receiving video were significantly more likely to use the scale, a finding that remained significant after controlling for nurses' education and years of experience, and for patient age and acuity. PMID- 1430465 TI - An overview of nursing ethics for nurse educators. AB - Nursing ethics is a topic included in most health care institutions as a requirement for accreditation by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). This article provides an overview of nursing ethics in a format that allows the reader to understand the basic principles while applying the information to daily work situations in a format for use in a classroom environment. The issue of dilemma recognition is addressed as well as mechanisms that may be used to facilitate dilemma resolution. Information is also provided for use in the development of skills in ethical decision-making. PMID- 1430466 TI - Long-term care nurses identify educational needs regarding quality assessment and improvement. AB - An increasing demand is being placed on nurses who are practicing in long-term care settings to conduct and/or participate in quality assessment and improvement (QAI) activities. A local survey of directors of nursing in long-term care indicated both personal interest and interest on the part of their staff nurses to attend continuing education (CE) programs regarding quality of care to increase their competencies in this area. Specific interest areas and recommendations for an educational offering regarding quality assessment and improvement for long-term care nurses are described. PMID- 1430467 TI - The basics of instructional design. PMID- 1430468 TI - Fibrous proliferations of infancy and childhood. PMID- 1430469 TI - Mutant p53 expression in solar keratosis: an immunohistochemical study. AB - Thirty-eight solar keratoses from 32 patients were studied for expression of mutant p53 protein by an immunohistochemical technique. Twenty-eight of the 38 solar keratoses (73.7%) showed positive and variable nuclear labelling, whereas 10 specimens were immunonegative. The nuclear immunopositivity which was seen in all variants was mostly diffuse in distribution. The adjacent "normal" epidermis of 8 keratoses showed positive mutant p53 labelling. Eight of the keratoses were associated with invasive squamous cell carcinoma of which only two were immunopositive. Cytoplasmic labelling was never a feature. The study demonstrates that mutant p53 protein is commonly expressed in all variants of solar keratosis and that its expression correlates with atypical keratinocyte proliferation. It is proposed that the demonstration of mutant p53 in the adjacent normal epidermis may be a potential marker of early neoplastic transformation. PMID- 1430470 TI - Immunohistochemical distribution of aromatase and 3B-hydroxysteroid dehydrogenase in human hair follicle and sebaceous gland. AB - Human hair follicles (HF) and sebaceous glands (SG) were assessed for the presence and distribution of the cytochrome P-450-aromatase (AR) and 3B hydroxysteroid dehydrogenase (3B-HSD) enzymes. Immunohistochemical methods were used to examine both enzymes in male and female human skin specimens at various ages and different body sites. AR was found in the external root sheath of anagen, terminal HF, and in SG, whereas the 3B-HSD was found only in the SG. AR was rarely found in telogen HF. The expression of both enzymes, AR and 3B-HSD, did not vary with body site or sex. Localizing AR in the external root sheath of anagen HF suggests that AR may have a function in the HF cycle. We hypothesize that AR may be one of many enzymes or factors that play a role in the HF cycle by regulating the level of androgens formed locally, whereas 3B-HSD is localized in SG, converting weak androgen precursors to potent androgens, stimulating lipogenesis. PMID- 1430471 TI - Cutaneous manifestations of measles in AIDS. AB - In immunocompetent patients, infection by the measles (rubeola) paramyxovirus produces fever, cough, coryza, Koplik's spots, and, on the skin, a macular erythema that can become confluent. The erythema has a striking cephalocaudal spread and clearing. The diagnosis of measles on a skin biopsy and the distinction from an erythema multiforme type of drug eruption can be difficult. We studied a skin biopsy from a patient with the acquired immunodeficiency syndrome (AIDS) who presented with measles. In contrast to erythema multiforme, the measles biopsy has necrosis of clusters of keratinocytes in the high spinous layer and granular layer of the epidermis, whereas erythema multiforme has necrosis of basal keratinocytes. Multinucleated keratinocytes may or may not be prominent in the measles biopsy. Cytoplasmic swelling of the keratinocytes in the granular layer may be present even when multinucleated cells are sparse. Immunoperoxidase reactivity for measles virus protein is present in intranuclear inclusions and in the cytoplasm of infected upper spinous keratinocytes. There were more cells with positive staining in the biopsy from the AIDS patient than in another biopsy from an immunocompetent patient with measles. The AIDS patient was seronegative for measles throughout the course of the illness. The examination of the skin biopsy can be very important in the diagnosis of measles in AIDS patients or immunocompromised patients who may not develop the usual diagnostic serology. PMID- 1430472 TI - Angiotropic malignant melanoma. Report of two cases. AB - Two cases of malignant melanoma are described that showed focal perineural invasion and exhibited striking tropism for small and medium-sized vessels, primarily veins. The melanoma cells proliferated within the vessel walls, expanding and replacing the muscle layer but sparing the endothelia. Intravascular invasion was not seen. Immunohistochemical studies confirmed the pattern of growth within vessel walls and the integrity of their endothelia. In one of the cases, similar vascular tropism was encountered in a capsular vein from a regional lymph node. We propose the term "angiotropic malignant melanoma" for this phenomenon and suggest that angiotropism may be a rare mechanism for melanoma spread and progression. PMID- 1430473 TI - Pleomorphic lipoma. Case report and discussion of "atypical" lipomatous tumors. AB - A case of pleomorphic lipoma is described. Pleomorphic lipoma is included in the "atypical" lipoma classification. Because of its atypical microscopic appearance, it must be differentiated from liposarcoma. We will discuss pleomorphic lipoma and its position in the classification of atypical fatty tumors. PMID- 1430474 TI - Multiple sclerotic fibromas of the skin. A cutaneous marker of Cowden's disease. AB - Multiple hamartoma syndrome, or Cowden's disease, is a rare genodermatosis with multiple organ system involvement in which malignancy, particularly of breast and thyroid, may develop. Multiple trichilemmomas have been classically regarded as the cutaneous hallmark of this disease. We here emphasize multiple sclerotic fibromas of the skin as another specific cutaneous marker of this entity, which may also be helpful in an early diagnosis. PMID- 1430475 TI - Biochemical activities of Bacillus species isolated from flat sour evaporated milk. AB - Forty strains of bacilli were isolated from flat sour evaporated milk and were characterized as Bacillus stearothermophilus (5 strains), Bacillus licheniformis (10 strains), Bacillus coagulans (15 strains), Bacillus macerans (5 strains), and Bacillus subtilis (5 strains). The hydrolases of these strains were examined with the API ZYM system, and the ability of these strains to produce acid in milk incubated at different temperatures was also examined. Esterase, esterase lipase, lipase, valine aminopeptidase, phosphoamidase, beta-glucuronidase, and beta glucosidase were the activities found in all strains tested; they were strain dependent and ranged between 1 and 5 by the API ZYM test. The same strains produced various concentrations of acid in milk. These organisms may be responsible for the flat sour spoilage in evaporated milk. PMID- 1430476 TI - Northern and in situ hybridization analyses of the effects of somatotropin on bovine mammary gene expression. AB - We investigated the potential roles of insulin-like growth factor-I and epidermal growth factor, both multifunctional regulators of mammary physiology, in somatotropin-stimulated lactation of dairy cattle. One insulin-like growth factor I mRNA (7.4 kb) was detected in lactating mammary tissue; however, it became undetectable after somatotropin administration. Four type I insulin-like growth factor receptor mRNA (11.3, 6.2, 4.9, and 3.3 kb) were detected in mammary tissue and primarily expressed in alveolar epithelial cells. All of these receptor mRNA markedly decreased in mammary tissue from somatotropin-treated animals, although the cellular distribution pattern of receptor gene expression did not change. One epidermal growth factor receptor mRNA (10.5 kb) was present in mammary tissue and predominantly expressed in alveolar epithelial cells. Epidermal growth factor receptor mRNA decreased after somatotropin administration. The results from this study are consistent with the idea that the stimulatory effect of somatotropin during lactation is in part due to its ability to regulate the expression of specific genes or the stability of their mRNA in mammary tissue. The data also suggest roles for insulin-like growth factor-I and epidermal growth factor, as well as their homologous receptors, in controlling cellular changes in the mammary gland during somatotropin-stimulated lactation. PMID- 1430477 TI - Use of augmented cultural techniques in the diagnosis of the bacterial cause of clinical bovine mastitis. AB - Preculture incubation, preculture freezing, and increased plate inoculation volumes were tested in an attempt to increase the recovery rate of pathogens in milk from cases of clinical bovine mastitis. Culture of milk from 291 cases of clinical bovine mastitis was performed using standard milk culture techniques (.01 ml of fresh milk streaked on trypticase soy agar plates with 5% sheep blood and .1% esculin). The sensitivity of this method was compared with that of cultures performed using augmented techniques: 4 and 18 h of preculture incubation; preculture freezing of samples overnight at -20 degrees C; and increasing the plate inoculation volume to .05 and .1 ml for fresh, incubated, and frozen samples. Preculture incubation and larger plate inoculation volumes significantly increased the recovery rate of bacterial pathogens over the standard culture method. The greatest improvement in sensitivity without a concomitant increase in contamination was achieved when samples were incubated for 4 h and plates were inoculated with .1 ml of the sample. Recovery was enhanced significantly by this method for several organisms, including environmental streptococci and coliform bacteria. Freezing milk before culture yielded a significantly higher positive culture rate overall, but freezing did not affect the positive culture rate of any individual bacterial species. PMID- 1430478 TI - Effects of a prostaglandin F2 alpha synchronization program in lactating dairy cattle. AB - A comparison was made between two different methods of reproductive management in the dairy cow. One protocol administered prostaglandin to open cows weekly; the other administered prostaglandin to open cows with a corpus luteum identified by rectal palpation. Survival analysis was used to analyze the data. Cows receiving weekly doses of prostaglandin had a 30% higher pregnancy rate (number of pregnancies per time) than the cows receiving prostaglandin based on rectal palpation of a corpus luteum. The average number of days to first insemination was shorter in cows given prostaglandin weekly. PMID- 1430479 TI - Effects of voltages on cows over a complete lactation. 1. Milk yield and composition. AB - The effect of long-term voltage exposure on milk yield and composition was assessed. Forty cows in second to fifth lactation were used. Four groups of 10 Holstein cows were exposed to either 0, 1, 2, or 4 V throughout an entire lactation. Each group was housed in a free-stall environment with bunk feed and water provided for ad libitum intake. Voltages (AC, 60 Hz) were applied between waterers and a metal grid. Cows could not drink without placing their front hooves on the metal grid. Individual records were maintained for milk weights, milk fat, protein, and somatic cell counts. Average actual (7312, 8527, 6938, and 7725 kg for groups exposed to 0, 1, 2, or 4 V, respectively) and mature equivalent (7802, 9281, 7308, and 8911 kg for groups exposed to 0, 1, 2, or 4 V, respectively) milk weights for 305 d showed no significant differences between groups exposed or unexposed to voltage. Average actual milk yields for 305 d in the previous lactations were 8016, 8163, 7679, and 7876 kg for groups exposed to 0, 1, 2, or 4 V, respectively. Somatic cell counts, milk fat, and protein showed no significant differences between groups exposed or unexposed to voltage. Feed and water intakes were not affected by voltage. PMID- 1430480 TI - Effects of voltages on cows over a complete lactation. 2. Health and reproduction. AB - For the effects of voltages on health and reproduction, 40 cows in second to fifth lactation were divided into four groups of 10. These included a control group that was not subjected to voltages and three treatment groups that were given either 1, 2, or 4 V at the water bowl. Cows in the treatment groups were exposed during the entire lactation to voltage whenever they drank. Voltages did not sufficiently affect milk yield. General health parameters studied were mastitis, hoof problems, and changes in body weight. Reproductive and calving parameters examined were days to first breeding, days open, services per conception, response to PGF2 alpha, calving intervals, visible abortion, and calves born dead. Voltages did not significantly influence cow health or reproductive performance. PMID- 1430481 TI - Cow sensitivity to electricity during milking. AB - Alternating currents were delivered to lactating cattle through the milk during milking. Electrodes were placed at the top of each short milk tube and jointed for one electrical contact. A metal grid on which the cows' rear hooves stood during milking was the second contact. Constant voltages (0 to 16 V) applied to contacts showed first lactation cows to be more sensitive than multiple lactation cows. First lactation cows kicked milking machines at 8 V (currents greater than 5 mA), and multiple lactation cows kicked at 16 V (currents greater than 8 mA). At lower voltages, there were no consistent significant differences in milking duration, milk yield, or composition for primary or residual milk. Application of constant currents of 5 mA for first lactation cows and 8 mA for multiple lactation cows produced no undesired behaviors but did result in some differences in production variables. Milking duration decreased during application of constant current to first lactation cows. Blood cortisol monitored in the multiple lactation cows during trial 2 showed a significant increase during milking but was equivalent or less during application of current. This study demonstrates that currents of 5 mA or less, delivered through the milk line, did not produce any direct economic effect. To produce this current, voltages on the milk pipe line would have to be in excess of 125 V (obvious human safety hazard) or in excess of 5 V on the claw of the milking cluster. PMID- 1430482 TI - Evaluation of pearl millet and field peas plus triticale silages for midlactation dairy cows. AB - A mixture of field peas and triticale was planted in spring, harvested as silage, and followed by a double crop of pearl millet, which also was harvested as silage. Eighteen Holstein cows were fed diets based on pea with triticale, pearl millet, or alfalfa plus corn silages. Dry matter digestibility of the pea with triticale diet was higher than for control (71.1 vs. 66.9%), but DM digestibility was not different between control and pearl millet diets. Milk production was not affected by diets containing pea with triticale or pearl millet compared with control diets (25.2, 23.2, and 24.5 kg/d). Cows fed pea with triticale produced milk with a higher concentration of fat (4.59 vs. 3.35%) and more FCM (27.3 vs. 22.1 kg/d) than those fed the control diet. However, cows fed the control diet gained more BW than those receiving pea with triticale or pearl millet diets. Partitioning of energy between body stores and milk production was different between cows fed pea with triticale and control diets; however, total energy use was not different (32.4 vs. 30.5 Mcal of NE(L)/d). Differences in energy partitioning may have been caused partly by differences in ruminal fermentation of the respective diets. PMID- 1430484 TI - Effect of graded concentrations of gossypol on calf performance: toxicological and pathological considerations. AB - The effects of feeding diets containing 0, 100, 200, 400, or 800 ppm of free gossypol were examined in 60 Holstein bull calves from 1 to 120 d of age. The concentrations of free gossypol were varied by varying amounts of cottonseed meals from three different sources. Cottonseed meal totaled 31% of each treatment ration. Feed consumption, BW, and blood parameters were collected on all calves at 30-d intervals throughout the trial. There were no significant differences between the groups for feed consumption, BW, or average daily gain. Changes in the group means for hematology and chemistry variables examined were modest and insufficient to distinguish diagnostically between safe and unsafe free gossypol concentrations for the different groups. Clinical evidence of disease was limited to the calves fed 400 or 800 ppm of free gossypol after 90 d of age. One calf in the group fed 400 ppm and 4 in the group fed 800 ppm died as a result of circulatory failure associated with gossypol consumption. We conclude from this study that a ration containing up to 200 ppm of free gossypol is safe, 400 ppm of free gossypol is toxic, and 800 ppm of free gossypol results in death losses. These results are compatible with previously reported naturally occurring toxicological outbreaks. PMID- 1430483 TI - Dietary cation-anion balance and cation source effects on production and acid base status of heat-stressed cows. AB - Two 4 x 4 replicated Latin square studies, each containing 8 lactating Holstein cows, were conducted simultaneously in south Georgia during the summer. The effects of dietary cation source (Na or K) and increasing dietary cation-anion balance (milliequivalents of Na + K - Cl per kilogram of feed DM) within cation source (control = 120.4 meq/kg of feed DM; Na source = 219.7, 347.8, 464.1 meq/kg of feed DM; K source = 231.2, 352.6, 456.0 meq/kg of feed DM) were determined on performance and acid-base chemistry during hot, humid weather. Cow body temperatures were elevated by environmental conditions but were not affected by dietary cation-anion balance. Differences in body temperature from dietary cation source probably were related to differences in cow BW. Intake of DM increased linearly, but yields of milk and FCM did not change with increasing dietary cation-anion balance, and cation source had no effect. Milk fat and protein percentages were not altered by dietary cation-anion balance, and greater milk fat and protein percentages from cows offered the Na versus K source diets probably were due to differences between cows in the two Latin squares. Alterations in blood acid-base chemistry with increasing dietary cation-anion balance were as expected. Greater blood buffering capacity, indicated by blood base excess and bicarbonate content, may be responsible for the improved feed intake. PMID- 1430485 TI - Estimation of heterogeneous variances using empirical Bayes methods: theoretical considerations. AB - Procedures are described to estimate variances when heterogeneity of genetic and residual dispersion parameters exists for some criterion. Genetic and residual variances are considered to follow distributions with either known or unknown parameters. The estimates of variances obtained are weighted averages of the corresponding parameter and of a data-based statistic. Although the techniques presented are largely inspired by Bayesian ideas, the procedures can be given a frequentist interpretation, and the parameters of the prior distributions can be estimated from the data at hand. Techniques are described and illustrated for situations in which animals are related or unrelated across herds. We conjecture that the proposed estimators have smaller mean squared error than those obtained by grouping observations in some way and then applying REML within each group. PMID- 1430486 TI - Estimation of heterogeneous within-herd variance components using empirical Bayes methods: a simulation study. AB - Genetic evaluation using BLUP can accommodate heterogeneous variances if the necessary variance components are known; this may require estimation of variance components within each heterogeneous subclass. Properties of sire and residual variance estimates obtained by an empirical Bayes approach, which combines within herd and prior estimates, were examined via simulation. Prior estimates were obtained using REML across herds, as if variances were homogeneous. Convergence was improved by incorporation of prior information such that variance component estimates could be obtained in within-herd situations for which a REML algorithm failed to converge. Accuracy of sire variance estimates was greatest when both within-herd and prior information were used, but improvement in accuracy of residual variance estimates associated with incorporation of prior information was minimal. Correlations between sires' standardized true transmitting abilities and PTA that used empirical Bayes variance estimates were larger than those obtained when heterogeneity was ignored. Proportions of sires selected, based on standardized PTA, from environments with differing genetic and residual variances became more uniform as the relative weight placed on within-herd data in variance estimation increased. Thus, useful variance component estimates can be obtained within individual herds by using empirical Bayes methods with across-herd estimates as prior information; this may allow prediction of breeding values that are less influenced by heterogeneous variances. PMID- 1430487 TI - A method for combining United States and Canadian bull evaluations. AB - Canadian and US genetic evaluations for July 1991 were combined for 3304 Holstein bulls evaluated in Canada that had US progeny or a cross-reference code. Canadian evaluations of the bulls and their sires and dams were converted to US PTA. Combined PTA were weighted averages of progeny information from both countries and parent average. Parent average was recomputed from the sire's combined evaluation and the dam's evaluation with the most daughter equivalents. Bulls were processed in birth year order so that combined evaluation of sire was available. Progeny contribution was adjusted to remove the influence of the bull's evaluation on progeny evaluations through their parent averages, which left only the portion that was due to progeny records and grandprogeny information. A weighted average of adjusted progeny contributions was combined with parent average to form a combined PTA more accurately than possible by averaging domestic and converted PTA. Combined reliability was computed by summing daughter equivalents from progeny and from updated evaluations of parents. Canadian daughter equivalents were multiplied by .9 to approximate US values. Combined evaluations simplify bull selection by providing comparable and complete information for bulls evaluated in two countries. PMID- 1430488 TI - Timing of insemination in dairy heifers. AB - Data representing 676 AI of 372 virgin dairy heifers during 1984 to 1987 at the University of Illinois were analyzed by analysis of variance to determine the effect of timing of AI on conception rate. Standing to be mounted, bawling, and attempting to mount were the three criteria used for determining the presence of estrus. More than 90% of the observations were conducted by one herdsperson between 0700 and 1600 h daily. Heifers were artificially inseminated with frozen semen from 58 bulls by one of two technicians. Conception rate on first AI was 56%, determined by return to estrus or 33- to 50-d rectal palpation for pregnancy. Conception rate to second and later AI was near 40%. Eighty-six percent of the heifers conceived during the trial. The average interval between first observation of standing estrus and AI was 10.5 h; the range was 15 min to 33 h. The model discussed contained six variables: time interval between first observation of standing estrus and AI (group), breed, sire within breed, year bred, season bred, and inseminator. The analysis of variance of conception to first AI showed timing of AI and service sire as the two most significant effects. Conception to first AI was worst when AI occurred 13.5 to 33 h after first observation of estrus. No factors considered were significant sources of variation for second or later AI. PMID- 1430489 TI - Current status and potential of embryo transfer and reproductive technology in dairy cattle. AB - Significant use of embryo transfer in dairy cattle commenced with the introduction of nonsurgical embryo recovery in the mid-1970s and developed with the use of nonsurgical transfers in the late 1970s. Numbers of registered Holstein calves from embryo transfer doubled yearly through 1980, after which the rate of increase slowed; the total reached nearly 19,000 calves in 1990. However, the efficacy of superovulation procedures and commercial success rates of transferred fresh embryos have not improved the past 10 to 15 yr. Fertilization rates in superovulated donors remain low. Although embryo-splitting techniques were perfected in the early 1980s, they are not used widely. A practical, commercial embryo-sexing procedure remains unavailable. Recent significant improvement is apparent in the technology of ultrasound-guided oocyte collection and in vitro oocyte maturation, fertilization, and embryo culture. In the future, this technology may be used in conjunction with sperm separated by sex with a flow cytometer. Modest numbers of embryo clones have been produced in several commercial programs via nuclear transfer techniques. However, the efficiency of gene transfer experiments involving ova of cattle and other domestic species has been low. Recently, DNA probe technology has begun to provide genotype information for cattle and will ultimately be applied to embryos. PMID- 1430490 TI - Structure of breeding programs to capitalize on reproductive technology for genetic improvement. AB - Potential rates of genetic progress are limited by biological constraints, which along with genetic parameters determine the structure of breeding programs to be employed for maximum genetic improvement. The objective here is to determine whether current progeny-testing programs in dairy cattle, which have been dictated and constrained by low female reproductive rates, need to be changed to capitalize on new reproductive technologies and how these changes should be implemented. Many differences between breeding programs diminish when selection on animal model genetic evaluations across all age and population groups is adopted as a strategy. Progeny-testing schemes then evolve toward dispersed open nucleus breeding schemes when multiple ovulation and embryo transfer is used on bull-dams. Nucleus breeding schemes have been advocated to capitalize on embryo transfer technology. In nucleus breeding schemes utilizing high reproductive rates, inbreeding, rather than reproductive rate, poses a limit to genetic progress, and strategies that maximize response to selection while limiting inbreeding need to be employed. One strategy is mating each dam to several sires rather than only one sire. In vitro embryo production techniques can be used to facilitate such mating strategies. Large-scale in vitro embryo production programs, in which large numbers of embryos per female are tested in the commercial population, offer the greatest potential for genetic gain with low rates of inbreeding. Cloning has an impact mainly on methods for dissemination of genetic improvement. Breeding herds, genetically inferior to marketed clones, are needed for continuous genetic gain. Reproductive technologies offer the potential for genetic improvement. Whether new breeding programs require changes in population structure, e.g., by creation of nucleus breeding herds, depends mainly on logistics and on quantity and quality of field information. PMID- 1430491 TI - Use of reproductive technology to estimate variances and predict effects of gene interactions. AB - Advanced reproductive techniques are creating the large numbers of close relatives needed to study gene interactions. Identical triplets, a set of 26 full sisters, a family of 4215 three-quarter sisters (same sire and maternal grandsire), a family of 76,698 half sisters, and 1.6 million granddaughters of Round Oak Rag Apple Elevation now have lactation records. Similarity of closest relatives might be explained by similar nonadditive as well as additive genetic merit. The 23,015 families of full sisters with mean family size of 3 provide nearly as much information about dominance variation as do the 55,779 families of three-quarter sisters with mean family size of 13; the 79 families of clones provide little information by comparison. Hypothetically, REML analysis of all US Holstein data could provide estimates of dominance and additive x additive variance with standard errors approximately 1% of phenotypic variance, but estimates of any higher order interactions would have standard errors greater than 10%. The tilde-hat approximation proved to be incompatible with animal models but was used for sire-maternal grandsire analysis of 765,868 first lactation records. Dominance variance was estimated as 3.5% of phenotypic variance for milk and 3.3% for fat with standard error of 4.2%. With constant data set size, variances are estimated most precisely if family sizes equal 1 plus ratio of within-family to between-family variance. An animal model evaluation including dominance relationships for 581,670 animals was computed, but gene interactions from distant ancestor pairs were ignored. Mating advice and improved additive predictions, especially for clones, could be obtained by including dominance in models. PMID- 1430492 TI - Optimal effective population size for the global population of black and white dairy cattle. AB - The replacement of other black and white cattle strains by the North American Holstein breed, which itself is dominated by a small number of elite sires, has reduced the genetic diversity of the global population. Intense selection on a global basis leads to rapid genetic improvement but reduces effective population size. The optimal global effective population size was chosen to maximize the net present value of all future benefits from the breeding program. Two separate discount rates were used to reflect concerns about the long-term costs of small effective population size. This led to a higher optimal number of bull-sires than in past analyses. The optimum was sensitive to the magnitude of inbreeding depression and to the discount rates, but not to the variance caused by new mutations and the size of the world population. The genetic correlation between the breeding objectives of different AI studs controls the extent to which they all select the same sires of sons and, hence, affects the global effective population size. The prediction is made that different countries will select partially different sires, but genetically isolated strains will not reemerge. A better global breeding program is likely when selection of sires takes account of inbreeding depression and small genotype by environment interactions. PMID- 1430493 TI - Achievement. Fear of success--fear of failure. PMID- 1430495 TI - Sealing of occlusal hidden caries lesions: an alternative for curative treatment? AB - The bacterial composition of the dentine of thirty molars with sealed occlusal surfaces (Delton tinted) was examined. Undiagnosed hidden caries was present at the time of treatment. Although clinically assessed as good (age 3.4 years, s.d. 2.1), 47 percent of the sealants had a marginal defect, when assessed with SEM. The dentine of the treated teeth was of a soft consistency. The median of the number of microorganisms was 400 (range 0-3.10(5)) cfu per sample. Mutans streptococci and lactobacilli were found in 53 percent of the samples. No relationship was found between the number of microorganisms and the marginal adaptation of the sealant, when examined under SEM; neither was a relationship found between the age of the sealant and the number of microorganisms (Kendall's Tau-C = 0.17, n.s. and -0.01, n.s., respectively). At present, there are insufficient grounds for treating nonvisible lesions (with a radiolucency on the bitewing) with a resin sealant. PMID- 1430494 TI - Preventive measures and caries progression: an in vitro study on fissures and smooth surfaces of human molars. AB - The aim of this study was to compare pit-and fissure sealants with fluoride treatments in their effectiveness to inhibit or reduce the progression of enamel lesions, particularly in the fissure region. The effects of fissure probing as used in diagnosis were compared with in the same protocol. Using a combination of image analysis of X-ray pictures of full crowns and a light microscopic evaluation of cross-sections provided information on the three dimensional spread of enamel demineralization. Pit-and-fissure sealants were superior in protecting enamel against progression of demineralization, as long as the walls of the fissures were well covered. The protection against demineralization offered by fluoride was mainly restricted to the smooth enamel surfaces; in fissures no protection could be measured. Surface defects of the enamel caused by probing or abrasion aided the progress of the lesion. PMID- 1430496 TI - Glass ionomer/resin preventive restoration. PMID- 1430497 TI - Hereditary dentinogenesis imperfecta: a treatment program using an overdenture. AB - The aim of treatment in cases of dentinogenesis imperfecta is to improve the esthetic appearance and maintain the oral masticatory apparatus in a healthy and functional state. In the growing child, it was decided to maintain the teeth for as long as possible under an overdenture, until such time when a permanent prosthetic solution can be decided upon. PMID- 1430499 TI - Possible hazards of the transpalatal bar: report of cases. PMID- 1430498 TI - Teenage luxation injury: report of case. AB - The endodontic, restorative, and orthodontic treatment sequence of the accidental injury of three maxillary incisors has been presented. The treatment objective was to achieve an esthetically acceptable result for a young adult, until a definitive fixed prosthetic restoration can be planned. The ankylosed maxillary right permanent central incisor (11) is being maintained for reasons of arch length space and alveolar bone height. PMID- 1430500 TI - Dens evaginatus: report of case of continued root development after Ca(OH)2 apexification. PMID- 1430501 TI - Effect of APF gel on a glass ionomer cement: an SEM study. AB - This SEM study evaluated the micromorphological effect of a 1.23 percent acidulated phosphate fluoridated gel (Oral B)(APF) on the surface of a glass ionomer cement (Ketac-Fil). Glass ionomer (GI) cylinders (area 6.69 mm) were prepared and divided into seven groups of ten specimens each: Group 1, glaze, no polishing; Group 2, glaze, polishing, glaze; Group 3, glaze, no polishing, APF for four minutes; Group 4, glaze, polish, glaze, APF for four minutes; Group 5, no glaze, no polish, APF for four minutes; Group 6, no glaze, polish, APF for four minutes; Group 7, glaze, polish, two coats of glaze, APF for four minutes. The glass ionomer was handled according to manufacturer's instructions, except for groups 5 and 6, where no glaze was used. Polishing was done with medium Sof Lex discs, using slow-speed and water. The glaze resin (Ketac-Glaze) was painted with a brush over the GI surface and cured with visible light (Demetron) for thirty seconds. In Group 7, the first coat was cured and then the second coat was applied. The APF was applied with a cotton applicator for four minutes, rinsed, and dried. All specimens were then mounted on aluminum stubs, coated, and evaluated under the SEM. The results indicated that the glaze tends to contract or incorporate into the GI matrix in all groups. When APF was used over the GI, the amount of glaze remaining over the surface was diminished, exposing the GI surface. When two coats of the glaze were used, minimal GI surface was exposed after APF treatment. PMID- 1430502 TI - Increasing interest in pediatric dentistry? AB - Increasing numbers of senior dental students anticipate careers in pediatric dentistry. A review is provided of the evolving dental student interests and some insight into these developments--particularly in terms of the increasing numbers of women in dental programs. PMID- 1430503 TI - The relationship of the changing structure of families and the health of children. AB - The changing family structure impacts on the physical and mental health, emotional state and academic performance of children. Children reared in other than a family with both biological parents have increased difficulties. Pediatric dentists will need to consider these realities in their treatment of an increasing diverse population of children. PMID- 1430504 TI - The assessment of two oral sedation drug regimens in pediatric dental patients. AB - Oral sedation remains a common method for managing uncooperative and/or extremely fearful pediatric patients requiring dental treatment. The purpose of this retrospective review is to report on the adverse reactions associated with the use of two oral sedation drug regimens commonly employed in pediatric dental patients. Of a combined total of 73 different patient records, 112 sedation cases from the pediatric dental program at the University of Alabama School of Dentistry were reviewed for this report. The two drug regimens were (1) chloral hydrate/promethazine and (2) meperidine/promethazine. Documentation was taken from the sedation cases, which included the following: (1) age, (2) weight, (3) the drug regimen and dosages, (4) the use of nitrous oxide, (5) the effectiveness rating of each sedation, and (6) adverse reactions. The adverse reactions included emesis and oxygen desaturation (hypoxemia) the latter being determined by the use of a pulse oximeter. The results of the study revealed that approximately 48 percent of the sedation cases with pulse oximetry recordings experienced mild to moderate hypoxemia, and in 6.2 percent of the cases, emesis occurred. The review and statistical analysis of the sedation ratings using the nonparametric analog of the t-test indicated no significant difference of effectiveness between the two drug regimens. This study shows that oxygen desaturation occurs frequently in pediatric dental patients being treated with conscious oral sedation techniques and that the prevalence of adverse reactions was similar for the drug regimens evaluated. PMID- 1430505 TI - Caries preventive effect of high fluoride and xylitol containing dentifrices. AB - Dental examinations were conducted in 1987 on 520 of the 753 children who fully participated in a three-year field-trial, 1983-1986, of the anticaries effect of dentifrices containing fluoride and xylitol. The prevalence of decayed (D), missing (M) and filled (F) permanent teeth differed significantly among the five treatment groups. Caries prevalence was inversely related to the level of fluoride, 1250, 2500 and 5000 ppm, in the dentifrice used, but was not associated with the presence or absence of 15 mg percent xylitol. The age, number of children, and number of erupted teeth were unequally dispersed among treatment groups. The DMF teeth scores showed non-normal distributions and nonhomogeneous variances. Following an exploratory scrutiny, the DMFT data were transformed to normal distributions for intra- and inter-treatment-group evaluation. All groups showed positive, significant regressions of DMF scores with the age of the children and an inverse significant regression with DMFT scores in relation to the fluoride content of the dentifrice under test. PMID- 1430506 TI - Dental biomechanics and the dental curriculum. AB - Attention is drawn to the numerous biomechanical concepts which provide the scientific basis for the many precepts taught in the various branches of clinical dentistry. It is suggested that dental biomechanics should logically be a subject area in its own right and that a practical way to achieve this would be for it to be gradually incorporated into the allied and complementary subject of dental materials science. PMID- 1430507 TI - Assessment of elderly people on entry to residential homes and continuing care arrangements. AB - Increasing numbers of elderly people are entering private residential homes in the UK. Results of surveys show poor oral health in this group. A survey was therefore conducted of 50 residential homes (housing 1337 residents) to determine assessment on entry and continuing care provision. In 38 per cent of homes no written notes were made of the initial assessment. Topics of dental interests were infrequently assessed on entry (only 16 per cent of carers examined the oral cavity, 52 per cent assessed the subject's ability to care for their dentures). Medical topics (mobility, incontinence, eyesight, etc) were all assessed in more than 80 per cent of subjects. Suggestions are made for utilization of an easy assessment questionnaire and improved denture naming arrangements. The importance of regular check-ups, education and publicity for this group is stressed. PMID- 1430508 TI - Finishing of amalgam restorations: a three-year clinical study. AB - Class I and Class II amalgam restorations were placed in the permanent teeth of 66 patients, each of whom received a minimum of three restorations. At least one of these restorations was carved-only, at least one was immediately finished (using a prophylaxis paste on rubber cups at low speed, 8 or 10 min after trituration), and at least one restoration was polished (using finishing burs and polishing points, more than 24 h after placement). The number of restorations available for assessment of marginal fracture using the 11-unit photographic scale developed by Mahler was 253 at baseline, 249 at 1-year and 2-year recalls and 228 at the 3-year recall. Although polished restorations exhibited greater initial (baseline) marginal fracture, at 1-year, 2-year and 3-year recalls the restorations were found to exhibit a similar amount of marginal fracture regardless of the finishing technique. The amount of perceived marginal fracture increased steadily after 1 year. The immediate finishing of amalgam restorations showed no long-term benefit over the other techniques and has little to commend it. The clinical finishing of amalgam restorations is discussed in the light of this and other research. PMID- 1430509 TI - Dental anxiety and attendance in the north-west of England. AB - The aim of this study was to record the level of anxiety and last recorded visit for a dental check-up of a random sample of 300 workers at three sites in the North-west of England. All subjects were asked to complete a short written questionnaire and 255 (85 per cent) usable forms were returned. The mean level of anxiety using the Corah Dental Anxiety Scale (DAS) (N.L. Corah, 1969, J. Dent. Res. 48, 596) was 9.1. Females had a statistically higher mean DAS than males but there was no correlation between DAS and either age or occupational status. Those subjects who claimed not to have had a check-up in the past year had a significantly higher mean DAS than those who claimed to have been in the past year. Multiple regression analysis showed that the reported time interval since the last check-up was the most important predictor of the DAS score. The implications of the results are considered for the future of restorative dentistry. PMID- 1430510 TI - Cardiopulmonary performance following changes in position and the administration of intravenous Diazemuls. AB - Twenty healthy volunteers entered a study to assess cardiopulmonary responses, as measured by pulse oximetry, following changes in posture in the dental chair and the administration of Diazemuls (diazepam) in doses sufficient to instill sedation (up to a maximum dose of 20 mg) in the volunteers to a degree such that ptosis was seen. The results indicate that SaO2 values remained above 95 per cent throughout the study. It is concluded that although changes in SaO2 and pulse rate do occur, these differences are not important in healthy individuals, although they may be more serious in patients with pre-existing cardiopulmonary disease. PMID- 1430512 TI - A preliminary investigation into the effect of increased occlusal vertical dimension on mandibular movement during speech. AB - Current methods of determining whether a patient will accommodate to an increased occlusal vertical dimension rely on a largely subjective assessment of the mandibular rest position and capacity to adapt whilst wearing a temporary appliance. The purpose of this preliminary study was to establish if mandibular movement during speech may provide an objective criterion in the assessment of adaptation to increases in occlusal vertical dimension. The closest speaking space, measured as the vertical distance between an incisor point and centric occlusion, as determined during pronunciation of sibilant speech sounds was chosen to depict mandibular movement. The closest speaking space was determined using a Sirognathograph for six young adult subjects and varied from a mean of 1.0 to 3.3 mm. An acrylic splint covering the entire occlusal surface of the lower arch, designed to increase the occlusal vertical dimension by 4 mm in the incisor region, was then cemented on each subject's mandibular arch. The closest speaking space was again determined after 5 days continuous wear of the splint and the mean values found to have decreased to a range of 0.0-1.0 mm. The differences between the mean values for the closest speaking space for each subject before and after splint wear were statistically significant. It was postulated that this method may lead towards an objective basis for deciding if patients will adapt to an increase in occlusal vertical dimension. PMID- 1430511 TI - Predictions of restoration deterioration. AB - This study evaluated the application of a mixture model involving a Weibull distribution function to predict the median times for restorations of three dental restorative materials to achieve unsatisfactory rating scores for six clinical factors. The accuracy of the method was assessed graphically against the known actuarial long-term deterioration observations of 1813 amalgam, 1774 anterior resin composite and 474 glass polyalkenoate (ionomer) cement restorations, assessed over periods of up to 20, 18 and 14 years, respectively. Of the six clinical factors investigated (which included marginal fracture), only four had sufficient long-term unsatisfactory rating score data to enable their median times to be predicted. These predicted times were: for amalgam restorations, surface roughness 32.5 years and surface tarnishing 16.0 years; for resin composites, marginal staining 25.4 years and colour mismatch 14.2 years; and for glass polyalkenoate (ionomer) cements, marginal staining 17.6 years and colour mismatch 3.6 years. The known and predictive unsatisfactory rating score results were generally in close agreement. However, it was not possible to predict median times for unsatisfactory rating scores associated with very slowly deteriorating restoration factors. The actual replacement rates of the amalgam restorations were too low to obtain their median survival time. However, for the faster failing resin composites this time was 7.9 +/- 0.5 years, and for the glass polyalkenoate (ionomer) cements 2.2 +/- 0.2 years. The relationship of restoration deterioration to restoration replacement and dental health requires further analysis. PMID- 1430514 TI - Close range photogrammetry--a clinical dental research tool. AB - Photogrammetry is the art, science and technology of obtaining reliable information about physical objects through processes of recording and interpreting photographic images. This review outlines the principles of the technique and summarizes the various methodologies and applications in clinical dental research. PMID- 1430513 TI - Dentine bonding agents--characteristic bond strength as a function of dentine depth. AB - The tensile bond strength to dentine of four dentine bonding agents has been measured at various depths within dentine and the results analysed using Weibull analysis. There were significant differences in the bond strength values among the four products particularly with near-surface dentine. Despite the differences in chemical composition among the materials the trend of decreasing bond strength with increasing depth of dentine was common to them all. This suggests that the underlying mechanism of adhesion may be common to all four products despite their differing chemical compositions. PMID- 1430515 TI - A denture base resin with low water absorption. AB - The aim of this study was to investigate poly(isobutyl methacrylate) as a potential denture base material. It was found to have very low water absorption but poor mechanical properties and a low glass transition temperature. The latter features render the material itself unsuitable for use as a denture base material, but indicated that isobutyl methacrylate may be a useful co-monomer for reducing water absorption. PMID- 1430517 TI - Closure of Loyola dental school. PMID- 1430516 TI - Bonding characteristics of a phosphonated anaerobic adhesive to amalgam. AB - The shear bond strength of a phosphonated anaerobic resin dental adhesive (Panavia-Ex) to amalgam was determined and clinically important parameters affecting the bond strength: amalgam type, surface finish and corrosion, were investigated. It is possible to bond to high copper set amalgam using this adhesive with a clinically useful shear bond strength. Three copper-enriched, single composition alloys were studied. One was a spherical alloy and two were lathe cut. The bond strength to one of the lathe-cut alloys was significantly lower than to the other two alloys. A significantly higher bond strength to aged lathe-cut amalgam than to fresh amalgam was found. However, Weibull analysis indicated that these latter changes were less consistent and indicated patchy, localized changes in the amalgam surface. The bond strength to the spherical alloy was significantly reduced by polishing with a finishing bur or Prophy-Jet. Therefore when bonding to a large amalgam restoration with such a phosphonated anaerobic adhesive, no polishing of the amalgam should be undertaken. PMID- 1430518 TI - The continuing education business. AB - The success and potential of school-based continuing dental education programs has been limited because they are based on an inappropriate model. The information needs of practicing professionals are quite different from the needs of students preparing for licensure. This article describes four purposes served by information: (a) education, (b) certification, (c) network building, and (d) decision support. Dental education focuses on the first two while a broader view with emphasis on the latter two is appropriate for continuing education. The business of educating professionals is different from the business of educating candidates for the profession. An alternative conception of continuing dental education is presented based on the needs of its clients. PMID- 1430519 TI - Implications of geriatric concepts for the prosthodontic curriculum. PMID- 1430520 TI - Setting a standard on the pilot National Board Dental Examination. AB - Norm-referenced and criterion-referenced approaches to setting a standard, or minimum passing score, were used with the pilot Part II National Board Dental Examination. The criterion-referenced approach used with the pilot is based on the Rasch measurement model. The standards and associated failure rates were found to be similar for both approaches. These findings as well as the advantages associated with using the Rasch model suggest that this criterion-referenced approach to setting a standard on the restructured Part II examination is appropriate. PMID- 1430522 TI - A survey of Nebraska high school guidance counselors concerning student recruitment in dental education. PMID- 1430521 TI - The influence of advanced general dentistry training on practice patterns of Iowa dental graduates. PMID- 1430523 TI - Teaching photography in dental schools. PMID- 1430525 TI - Is a career in research oriented academics for you? PMID- 1430524 TI - Statement on the dedication of SUNY-Stony Brook's new building for the School of Dental Medicine. PMID- 1430526 TI - Curriculum guidelines for postdoctoral oral diagnosis/oral medicine. Section on Oral Diagnosis/Oral Medicine of the American Association of Dental Schools and the Organization of Teachers of Oral Diagnosis. PMID- 1430527 TI - Curriculum guidelines for predoctoral oral pathology. Section on Pathology of the American Association of Dental Schools. PMID- 1430528 TI - Dental students' self-assessed competence in geriatric dentistry. AB - This study measured the self-assessed confidence levels of four classes of dental students (n = 172) exposed to both didactic and clinical training regarding geriatric patients. It was found that after completing a two-term (20-week) didactic course in their junior year, and a five-week clinical course with geriatric patients in their senior year, dental students graduating from this university between 1987 and 1990 perceived significant improvements in their abilities to manage geriatric patients in all areas assessed, most notably in their treatment planning skills, in coordinating preventive dentistry programs, in referring patients to appropriate community resources, and in providing dental care in alternative settings. Greatest self-assessed improvements were exhibited between pre-didactic and post-didactic assessments, with a tendency to stabilize rather than improve after the clinical experience. Interestingly, this study found that the students' self-assessed changes between post-didactic training and post-clinical training were significant in only one area--their ability to manage the medical emergencies of elderly patients, including a patient's death in the dental chair. No differences were found between students who completed the clinical course early in their senior year with those who took it later; nor did differences emerge among the four classes. Clinical teaching in geriatrics may be an opportunity to practice skills and reinforce knowledge that has been gained in didactic courses, not necessarily a place to enhance perceived competence. PMID- 1430529 TI - Determinants of dentists' geographic distribution. AB - Practice location may have greater economic importance today for dental students and dentists who are considering relocation and/or expansion to new sites than in the past. Yet, a literature review easily leads to the inference that practice location decisions are far too complicated and individualistic for there to be any systematic pattern of dentists' geographic distribution. This paper specifies and estimates an economic model that attempts to explain the distribution of dentists in particular market areas in the state of Connecticut and to test the hypothesis that the distribution, rather than exhibiting randomness, adheres to the prediction of theory. The findings show that the geographic distribution of dentists is significantly related to a few key variables. Given these results, and because this model can be applied to other areas and uses data that are readily available for any market area, it may be useful for educators involved in helping dental students with their practice location decisions. PMID- 1430531 TI - Preliminary evaluation of an educational outcomes assessment process for dental interpretive radiography. PMID- 1430530 TI - Instrument effects on smoothness discrimination. AB - Dental and dental hygiene faculty must select instruments to be used for root surface evaluation during scaling and root planing procedures. Because little information has been reported comparing the effectiveness of various instruments for this task, selection is based on subjective opinions. This study examined differences in the ability of 30 experienced and 32 inexperienced dental hygiene clinicians to differentiate degrees of surface smoothness using five different dental instruments. The relative smoothness test consisted of a set of ten paired abrasive strips of different or the same grit size. Repeated measures ANOVA revealed significance for both main effects, instrument used and experience level. All subjects made more correct assessments with the Williams probe, 3A explorer and Moffitt-MD probe than with the #17 explorer. There was no significant difference between the 3CH explorer and the other four instruments. Experienced clinicians scored significantly higher than students on the relative smoothness test. Instrument selection could affect the end products achieved by clinicians, as well as affecting validity and reliability of current clinical evaluation mechanisms. PMID- 1430532 TI - Long-term retention after self-instructional methods. PMID- 1430533 TI - Faculty participation as students in dental school academic programs. PMID- 1430534 TI - An introductory course in dental computing and research methods. PMID- 1430535 TI - Curriculum guidelines for neuroanatomy. Section on Anatomical Sciences of the American Association of Dental Schools. PMID- 1430536 TI - Curriculum guidelines for predoctoral biochemistry. Section on Biochemistry and Nutrition of the American Association of Dental Schools. PMID- 1430537 TI - Curriculum guidelines for predoctoral periodontics. Section on Periodontics of the American Association of Dental Schools. PMID- 1430538 TI - Trichloroacetic acid peel of molluscum contagiosum in immunocompromised patients. AB - Seven human immunodeficiency virus-(HIV) positive patients with biopsy proved extensive facial molluscum contagiosum were treated with trichloroacetic acid peels. Peels were performed with 25 to 50% trichloroacetic acid (average 35%) and were repeated every 2 weeks as needed. A total of 15 peels were performed with an average reduction in lesion counts of 40.5% (range 0 to 90%). No spread of molluscum lesions, scarring, or secondary infection developed at 2 months' follow up. Trichloroacetic acid peeling in concentrations of 35% or less appears to be a safe, effective, adjuvant therapy in the treatment of extensive molluscum contagiosum in immunocompromised patients. PMID- 1430539 TI - EMLA. A new and effective topical anesthetic. AB - A eutectic mixture of local anesthetics (EMLA) contains 2.5% lidocaine and 2.5% prilocaine in an oil and water emulsion and has been found to give effective, safe analgesia on normal and diseased skin, making it useful for numerous medical and surgical procedures, such as anesthesia for superficial surgery, split thickness skin grafts, venipuncture, argon laser treatment, epilation, and debridement of infected ulcers. Other indications have included use in postherpetic neuralgia, hyperhidrosis, painful ulcers, and inhibition of itching and burning. To be effective, EMLA should ideally be applied to the desired area for at least 1 hour under an occlusive dressing. The medication has been approved since May 1991 in Canada for use on intact skin and has been available in Europe for many years. This study discusses the background, efficacy, and current and potential uses of EMLA. PMID- 1430540 TI - Restoration of curved earlobe configuration with scar tissue advancement flap combined with second-intention wound healing. AB - Reconstruction of earlobe curvature in a scar-deformed and displaced earlobe was accomplished by a combination of 1) hypertrophic scar debulking, 2) partial defect closure by scar tissue flap advancement to re-establish the cephalic extent of the neck at the infralobular crease, and 3) second-intention healing of the noncovered lower earlobe, preserving its surgically re-established curved configuration. Although this article specifically addresses scarring deformities of the earlobe, the same principles could be applied to congenital, noncicatricial tenting deformities. PMID- 1430541 TI - Efficacy of double gloving as a protection against blood exposure in dermatologic surgery. AB - Double gloving has been widely suggested as a means of decreasing exposure to blood and other body fluids. However, most dermatologists do not routinely follow this practice when performing surgical procedures because it reduces manual dexterity and increases costs. To determine whether double gloving should be routinely practiced in dermatologic surgery, pairs of sterile surgical gloves worn during weekly UCLA dermatologic surgery clinics were collected over a period of 3 months and examined for perforations. The procedures gloves were used for ranged from excision of benign lesions, lasting 15 minutes, to hair transplants, lasting 3 hours. Upon completion of the procedures, 8 (5.5%) of 144 pairs of single gloves, 2 (3.7%) of 54 pairs of double inner gloves, and 3 (5.5%) of 54 pairs of double outer gloves were found to have perforations. There were no instances of both the double outer and the double inner gloves having perforations when worn on the same hand. This suggests that double gloving offers a protective advantage by providing extra protection for both the surgeon and the patient during dermatologic surgery. PMID- 1430542 TI - Dissecting folliculitis of the scalp. A case report of combined treatment using tissue expansion, radical excision, and isotretinoin. AB - Dissecting folliculitis of the scalp can develop into an extensive, hypertrophic scarred lesion that is unresponsive to routine treatment. In these situations, radical excision of the affected area and concurrent perioperative treatment with isotretinoin (13-cis-retinoic acid) may be effective. The authors describe a case, illustrating the successful clinical application of this technique. PMID- 1430543 TI - Predisposing factors of varicose and telangiectatic leg veins. AB - Presented is an epidemiologic study on predisposing factors in telangiectatic and varicose leg veins on 500 female patients. Genetic predisposition, hyperestrogenemic states, standing vocations, and obesity were found to be the major predisposing factors. Recognition of these factors may help to prevent further progression of proliferative venous disease after sclerotherapy in susceptible individuals. PMID- 1430544 TI - Influence of estrogens and progesterone on the venous system of the lower limbs in women. AB - Treatments with estrogens and progestogens are suspected of causing vascular complications either directly or by metabolic consequences. Although many studies have demonstrated an increased incidence of arterial and deep venous thrombosis, since 1970 the dose of estrogens and progesterones have been lowered with a proportional lowering of side effects. After classification of estrogens and progestogens, we studied their peripheral vascular effects. In our study, we demonstrated that the effects of estroprogestogen treatment on the superficial venous system depend on the dose of estrogen and progestogen. PMID- 1430545 TI - Recurrent varicose veins. Part 2: Injection of incompetent perforating veins using ultrasound guidance. AB - Treatment options following duplex evaluation of recurrent varicose veins are discussed and a method of injecting incompetent perforating veins using ultrasound guidance is described. The results of duplex evaluation 6 months postinjection using this technique are presented. These early results indicate that sclerosant injection employing ultrasound guidance is an effective and safe method of treating incompetent perforating veins. PMID- 1430546 TI - Modifications of electrosurgery electrodes. AB - Dermatologists often find that electrosurgical electrodes that are commercially available do not always suit their specific clinical requirements. Some physicians modify electrodes to achieve specific electrosurgical effects. The more popular modifications have given rise to new varieties of commercially available electrodes. PMID- 1430547 TI - Stents for nasal vestibule. AB - A method employing vinyl polysiloxane and polyethylene chemical tubing to make nasal stents is described. Vinyl polysiloxane stents, when well molded, are comfortable and easily tolerated. The technique has been useful for maintaining patent nares and enhancing graft viability. PMID- 1430548 TI - Running vertical mattress suturing technique. AB - The running vertical mattress suturing technique is a quick and simple method of providing skin edge eversion that is equivalent to the simple vertical mattress technique. The running stitch is relatively easy to master and provides excellent apposition of wound edges. PMID- 1430549 TI - Iontophoretic administration of lidocaine anesthesia in office practice. An appraisal. AB - BACKGROUND: Obtaining anesthesia for dermatologic, office-based surgeries often involves the pain of needle stick and burning upon injection of local anesthetic agents. No truly effective method for obtaining painless anesthesia is well accepted in the United States. OBJECTIVE: A study was carried out using iontophoresis of lidocaine with epinephrine to determine the practicality of this method of delivering local anesthesia prior to invasive procedures in dermatology offices. METHODS: A two-center, open-label study was undertaken using iontophoretic administration of 4% lidocaine with epinephrine 1:50,000 before painful procedures occurring in the dermatologists' office. RESULTS: Ninety-four procedures in 64 patients were evaluated. Both patients and physicians recorded 51% of procedures as painless, 36% as minor (partial), and 14% causing moderate to severe pain. Iontophoretic local anesthesia was 80 to 100% effective for pain relief for injections, abrasions, laser surgery, and cautery; it was significantly less effective in effecting pain relief for dermal excisions. CONCLUSIONS: Iontophoretic administration of anesthesia is a useful adjunct to the armamentarium of dermatologists performing surgical procedures in their office. PMID- 1430550 TI - Single hair transplantation using the Choi hair transplanter. AB - A new procedure for single hair transplantation using the Choi hair transplanter is presented. This operation provides obvious cosmetic advantages in hairline refinement and the reconstruction of eyebrows, eyelashes, beards, and pubic escutcheon. The surgical technique is described in detail. PMID- 1430551 TI - Primary cutaneous B-cell lymphoma. Diagnosis, treatment, and prognosis. AB - BACKGROUND: An elderly woman with B-cell lymphoma confined to the skin of the lower extremity was treated with combination chemotherapy and radiation therapy. She relapsed with new skin lesions outside the original radiation port that responded to additional radiation therapy and remains in remission 12 months after her last treatment. OBJECTIVE: This article investigates the diagnosis, treatment, and prognosis of primary cutaneous B-cell lymphoma. METHODS: The relevant literature was researched through computer data bases and bibliographies. RESULTS: Patients who present with localized lesions of primary cutaneous B-cell lymphoma have a favorable prognosis regardless of the type of therapy, although relapses may occur in the absence of systemic disease. CONCLUSION: We advocate the use of local therapies as initial treatment in patients with localized primary cutaneous B-cell lymphoma. PMID- 1430552 TI - Deoxyribonucleic acid (DNA) ploidy and proliferative characteristics of metastatic squamous cell carcinoma determined by flow cytometric analysis. AB - BACKGROUND: The deoxyribonucleic acid (DNA) index and the proliferative index (the fraction of cells in the S phase) can be independent prognostic indicators of the biologic aggressiveness of certain malignant neoplasms. OBJECTIVE: To determine whether the DNA index or proliferative index could predict metastases in cutaneous squamous cell carcinoma. METHODS: Nineteen different metastases from 15 patients with primary cutaneous squamous cell carcinoma (SCC) were reviewed, graded, and had DNA proliferative indexing performed by fluorescent activated cytometry. A control group of 13 patients with primary cutaneous SCC without metastases were studied in a similar manner. RESULTS: No significant difference between the metastatic and the nonmetastatic SCC groups for either DNA index or proliferative index (non-paired t-test) was observed. No correlative association with histologic grading with DNA index or proliferative index was observed for either group. CONCLUSION: We conclude that aneuploidy and S-phase fraction by fluorescent activated cytometry are not significant predictors of potential metastases in cutaneous squamous cell carcinoma. PMID- 1430553 TI - Microlipoinjection for the elevation of depressed full-thickness skin grafts on the nose. AB - BACKGROUND: Full-thickness skin grafts on the dorsum of the nose may heal depressed and might benefit from elevation. Microlipoinjection has been used to elevate depressed tissue; however, the long-term persistence of the augmentation is questioned. OBJECTIVE: To determine whether microlipoinjection beneath depressed full-thickness grafts on the dorsum of the nose can provide effective and persistent graft elevation. METHODS: Microlipoinjection was performed at one to three sessions under depressed full-thickness skin grafts on the nose of four patients. Their appearance was assessed clinically and photographically for the amount of correction at their last postmicrolipoinjection visit. RESULTS: All four patients had clinically significant elevation of their full-thickness skin graft. In the two patients followed for over 3 years, significant augmentation persisted. CONCLUSION: Microlipoinjection can provide cosmetically useful soft tissue augmentation under depressed full-thickness skin grafts; this augmentation can persist. PMID- 1430554 TI - The importance of bicarbonate in large volume anesthetic preparations. Revisiting the tumescent formula. AB - BACKGROUND: The tumescent local anesthetic approach is now being used more widely in dermatologic surgery. Although the original formula contains 12.5 mEq sodium bicarbonate per 50 mL of lidocaine, traditionally buffered solutions contain 1 mEq per 10 mL. OBJECTIVE: This study examines the effects of changing the concentrations of sodium bicarbonate in the tumescent formula. METHODS: Various concentrations of sodium bicarbonate in tumescent anesthetic preparations were measured for pH. RESULTS: Tumescent anesthetic preparations containing 5 mEq/L have a more physiologic pH (7.41) than the classic formula of 12.5 mEq/L (7.73). Clinical use of this reduced sodium bicarbonate solution showed no difference from the original formula. CONCLUSIONS: Sodium bicarbonate can be used in a 1 mEq per 10 mL of lidocaine ratio similar to other buffered anesthetic solutions. This solution is physiologic in pH. However, some thought should also be given to the pKa of lidocaine, which is at pH 7.9. To achieve this even higher concentration (20 mEq/L) bicarbonate must be added to the tumescent solution. Thought must be given to these concepts when tumescent solutions are used in large volumes. PMID- 1430555 TI - Scar wars strategies. Target collagen. AB - Hypertrophic scarring and keloid formation are clinical problems with effectively limited solutions. Although numerous methods have been devised to combat them, this article focuses on promising pharmacologic strategies that target collagen metabolism. Laboratory investigations of amino-acid analogs, procollagen peptides, D-penicillamine, and pentoxifylline have demonstrated them to be effective inhibitors of collagen synthesis in cultured cells and/or in animal models. Clinical trials of intralesional administration of interferons have shown impressive reductions in the size and collagen production of keloids. Furthermore, interference of extracellular matrix-enhancing cytokines, such as TGF-beta, may be an effective solution to keloids and hypertrophic scars. Additional research of soluble cytokine receptors, autoantibodies to cytokines, cytokine receptor antagonists, and cytokine-binding molecules may lead to the development of better therapeutic agents. PMID- 1430556 TI - The postoperative use of wound adhesives. Gum mastic versus benzoin, USP. AB - Our results, combined with the work of previous authors, show that gum mastic not only offers superior adhesive qualities compared with benzoin, USP but also has a lower incidence of postoperative contact dermatitis and subsequent skin discoloration. In light of the widespread use of surgical adhesives, this study is important in documenting the low incidence of complications and the advantages of gum mastic compared with benzoin, USP. PMID- 1430557 TI - Modified electrosurgical adapters. AB - BACKGROUND: Allegedly because of concerns over worker safety in removing spent needles from the Bernsco adapter a new, modified Luer-lok adapter has been introduced by the manufacturer. However, the new adapter frequently holds needles too loosely. OBJECTIVE: To introduce a modification of the original adapter design. METHODS: The end to be inserted into the needle hub was hollowed and trisected to allow flexibility of the phalanges. A small hole is drilled in the distal shaft to allow the placement of a spiral wire, allowing a snug fit even in older, well used electrosurgical handles. CONCLUSION: The modified electrosurgical adapter may facilitate needle removal and increase surety of fit with most electrosurgical handles. PMID- 1430558 TI - Alginates. A "new" dressing alternative. AB - BACKGROUND: Currently, a wide variety of bio-occlusive dressing materials are available. In general, these dressing materials provide a moist wound healing environment that has been shown to promote healing in both human and animal studies. To effectively use these dressings the clinician must have a full understanding of the properties of the materials as well as the pathophysiology of the particular wound. Most recently, a "new" biosynthetic dressing material, the alginates, has become available. OBJECTIVE: To highlight proper use of alginate dressings for the management of acute and chronic wounds. METHODS: Case study and literature review. RESULTS: Alginates were shown to be effective in a wide variety of acute and chronic wounds. CONCLUSION: Alginates possess several unique properties that should prove useful to the dermatologic surgeon as well as the dermatologist. Proper patient selection and use of this "new" dressing material, as well as a review of the literature is presented. PMID- 1430559 TI - The paramedian scalp reduction with posterior Z-plasty. A technique to minimize the "slot" defect. AB - BACKGROUND: One consistent and undesired sequela resulting from scalp reductions has been the "slot" or "trough" defect, referring to the scar following the final reduction. Attempts to correct this have not been entirely satisfactory. OBJECTIVE: To present an approach to minimize the "slot" defect that consists of staged modified paramedian scalp reductions combined with a large posterior Z plasty during the final reduction. METHODS: A paramedian crescent-shaped ellipse was marked onto the patient's scalp parallel and adjacent to the existing fringe hair. Subsequent reductions were performed in a similar manner approximately 2 months apart. The final reduction consisted of mobilization and transposition of the large flaps used in the posterior Z-plasty. RESULTS: Patients who underwent the staged modified paramedian reductions combined with a posterior Z-plasty had significant minimization and adequate camouflage of the undesirable "slot." CONCLUSION: Combining a large posterior Z-plasty with a paramedian reduction minimizes the slot defect. PMID- 1430560 TI - Fixed-tissue micrographic surgery in the treatment of cutaneous melanoma. An overlooked cancer treatment strategy. AB - Many physicians have overlooked the value of adding zinc chloride tissue fixation prior to Mohs micrographic surgery, partly because of the absence of randomized clinical comparison trials. Nevertheless, historic control data indicate a survival benefit in the treatment of cutaneous melanoma. Three possible mechanisms are: 1) prevention of release of viable cells into circulation during surgery, 2) avoidance of disruption of clinically invisible satellite deposits, and 3) stimulation of a local inflammatory reaction and possible immune response. PMID- 1430561 TI - Special issue: Oculopastic surgery. PMID- 1430562 TI - Eyelid anatomy. AB - BACKGROUND: The following anatomic information concerning the complex structure of the eyelids is distilled from gross and histologic study as well as surgical experience. OBJECTIVE: Our aim is to familiarize the reader with eyelid anatomy. CONCLUSION: Appropriate shape, contour, height and mobility of the lids are essential to adequate protection and function of the eyes as well as overall appearance. A thorough understanding of eyelid anatomy is therefore necessary to achieve optimal surgical results. For the purpose of this discussion the eyelids can be divided into the following structural planes: 1) skin and subcutaneous tissue; 2) orbicularis muscle and submuscular fibroadipose layer; 3) orbital septum; 4) preaponeurotic fat; 5) eyelid retractors; and 6) the tarsi and conjunctiva. PMID- 1430563 TI - Oculoplastic surgery. An overview. AB - BACKGROUND. The interface between the subspecialties of dermatologic surgery and oculoplastic surgery is broad. However, there are many commonly seen oculoplastic conditions that are not foremost in the mind of the dermatologic surgeon. OBJECTIVES. Common oculoplastic problems are detailed in this article and should provide the reader with a basis for understanding the wide spectrum of oculoplastic problems encountered in practice. PMID- 1430564 TI - Lumps and bumps of the eyelids and their management. AB - BACKGROUND: Tumors of the eyelids, because of their location and variety, can present management problems. OBJECTIVE: To describe tumors of the eyelid, their identification, and their management. CONCLUSION: All tumors and inflammations of the lids, except those that are easily diagnosed, should be biopsied and sent for histologic administration. PMID- 1430565 TI - Benign eyelid lesions. AB - BACKGROUND: Benign eyelid lesions include a diverse group of tumors, infections, and degenerative lesions that require specialized care for identification and treatment. OBJECTIVE: Diagnosis of benign eyelid lesions based on their clinical characteristics with pathological confirmation by biopsy where indicated. METHODS: Clinical evaluation, biopsy, and treatment with medication, surgery, and laser surgery are utilized. RESULTS: Improvement or complete resolution of these eyelid lesions is possible. CONCLUSION: Special care is necessary to avoid ocular complications that could compromise vision, comfort, and cosmesis. PMID- 1430566 TI - Malignant lesions of the eyelids. AB - BACKGROUND: The ocular adnexal area contains virtually every tissue type; nearly any type of malignant tumor may develop in this area. However, the vast majority of malignant eyelid tumors are carcinomas. Three types of carcinomas produce most of the malignancies in this group. They are: basal cell carcinomas, squamous cell carcinomas, and sebaceous cell carcinomas. OBJECTIVE: The management of these three tumors is discussed. METHODS: A review of current treatment options for eyelid malignancies was performed. RESULTS: A summary of the current treatment of the three most common eyelid carcinomas is discussed. CONCLUSION: With early recognition and appropriate management of eyelid malignancies, an extremely favorable prognosis can be obtained. The management is twofold and consists of curing the patient of the malignancy and then restoring the form and function of the eyelid in order to save the eye if possible. PMID- 1430567 TI - Closure of eyelid defects. AB - BACKGROUND: Repair of eyelid defects can be achieved by an array of procedures. OBJECTIVE: To provide a basic approach to repairing eyelid defects. METHODS: Defects are categorized by size. The method of repair for each defect is described. CONCLUSION: By selecting the proper method of closure, with due consideration of the size, location, and configuration of the defect, the cutaneous surgeon can repair eyelid defects whilst maintaining the best possible function and cosmetic appearance. PMID- 1430568 TI - Periocular flaps. AB - BACKGROUND: Most flaps used in periocular reconstruction are random pattern flaps. OBJECTIVE: To discuss the principles of periocular flaps as they relate to oculoplastic surgery, with an emphasis on reconstruction of the eyelids and ocular adnexa. METHODS: The advantages, disadvantages, and techniques of reconstruction are reviewed. CONCLUSION: The ability to conceptualize and utilize flaps in periocular surgery enormously extends the surgeon's capabilities to produce optimal results for the patient. PMID- 1430569 TI - Lateral canthoplasty. AB - BACKGROUND. Lateral canthoplasty is one of the most valuable procedures in ophthalmic plastic surgery and has a variety of indications. These include the repair of ectropion, paralytic lagophthalmos, and eyelid retraction. The procedure can also be used in the prevention of some of the above entities, in the delivery of orbital tumors, and is a valuable adjunct in lower blepharoplasty. The tarsal strip procedure is probably the most popular technique of horizontal shortening of the eyelid. OBJECTIVE. Indications for this procedure are reviewed. The technique as I perform it is described in detail. PMID- 1430570 TI - Considerations in aesthetic eyelid surgery. AB - BACKGROUND: Successful aesthetic eyelid surgery is based upon multiple complex factors that, when put together, yield a pleasing result. Beauty is inherently related to normal eyelid function and symmetry. OBJECTIVE: To review the critical issues facing the aesthetic surgeon, and to propose a systematic method of assessing the patient preoperatively. METHODS: This article first examines the general considerations for aesthetic eyelid surgery, followed by specific concerns within each anatomic area. RESULTS AND CONCLUSION: The critical task in aesthetic eyelid surgery is to reconstitute or preserve the normal structure and function of the eyelids. This is especially true in the multicontoured areas. It is essential for the surgeon to define the problems in a hierarchal fashion, and plan the surgery accordingly. Thus, not all patients can achieve the desired results in one sitting. The goal of aesthetic surgery is to avoid the telltale signs of surgery and to help the patient attain a youthful and energetic appearance for his or her age bracket. PMID- 1430571 TI - Upper eyelid blepharoplasty. AB - BACKGROUND: The surgical removal of redundant upper eyelid skin along with the excision of prolapsed anterior orbital fat is one of the most popular elective cosmetic surgical procedures performed today. OBJECTIVE: To provide a brief overview of patient selection and upper eyelid blepharoplasty technique. CONCLUSION: Through careful patient selection and preoperative evaluation in addition to a thorough knowledge of eyelid and orbital anatomy, good outcomes from upper eyelid blepharoplasty can be obtained. PMID- 1430572 TI - Lower eyelid blepharoplasty. AB - BACKGROUND: Lower eyelid blepharoplasty is a frequently performed procedure to reverse partially gravitational aging effects on eyelid tissues. Careful planning, proper execution, and appropriate management of potential postoperative complications will generally result in a happy and satisfied patient. However, in any surgical procedure that is primarily aesthetic in nature, the surgeon needs to be constantly aware of factors that may compromise the functional integrity of the eyelid. A patient with altered visual function or ocular discomfort is no longer primarily concerned about the final aesthetic appearance of even the most perfectly executed, technically correct blepharoplasty procedure. OBJECTIVE: To describe the preoperative evaluation, surgical technique, and postoperative complications of lower eyelid blepharoplasty. Specific attention will be given to lower eyelid retraction and ectropion following blepharoplasty. CONCLUSION: Successful lower eyelid blepharoplasty surgery can be a source of both patient and physician satisfaction. As long as patient expectations are consistent with realistic surgical goals, lower eyelid blepharoplasty is an important aspect of overall facial aesthetic surgery. PMID- 1430573 TI - The preseptal and the retroseptal approaches in transconjunctival blepharoplasty. AB - BACKGROUND: Although transconjunctival blepharoplasty was first described in the beginning of this century, it did not start to become popular until recently. OBJECTIVE: To describe the best approaches to transconjunctival blepharoplasty and their applications. CONCLUSIONS: There are two distinct approaches in this technique: the preseptal and the retroseptal. While not easier in execution, and at times it can be more difficult than the transcutaneous approach, the transconjunctival blepharoplasty has definite advantages. It belongs in the armamentarium of surgical procedures of all physicians performing cosmetic surgery. PMID- 1430574 TI - Nuances in ophthalmic plastic surgery. A dermatologic surgeon's perspective. AB - BACKGROUND: Presented several nuances in the performance of cosmetic upper, lower, and lateral eyelid surgery. OBJECTIVE: To provide slight modifications in the performance of cosmetic upper and lower eyelid surgery that may be timesaving and outcome-enhancing. Lateral eyelid tightening is discussed. The expected outcomes and best candidates for surgery are also described. METHODS: Methods vary with the individual procedure. However, expertise in the traditional methods of cosmetic eyelid surgery is integral to success with the modified techniques. RESULTS: Results vary with the individual procedure, the surgeon's expectations, and the surgeon's interpretation of the patient's expectations, as well as other factors. CONCLUSION: Modifications of traditional cosmetic eyelid surgical procedures may benefit the patient following careful planning and technique execution. PMID- 1430575 TI - Complications of blepharoplasty and their management. AB - BACKGROUND. Blepharoplasty is the most frequently performed cosmetic procedure on the face. Although complications are rare, their consequences can be devastating both the for patient and the surgeon. OBJECTIVE. The complications of blepharoplasty and their management are reviewed. PMID- 1430577 TI - [Body temperature, internal energy and the probability of the existence of warm blooded animals and man]. AB - Based on statistical peculiarities of the existence of two-leveled thermodynamic systems, it was shown that the probability of existence for warm-blooded organisms is determined by body temperature, energy of metabolism, and thermodynamic potentials of critical increase and decrease in the body temperature. It was established that the dynamics of human death rate from the birth to extreme old age is conditioned by age-related changes in the energy of metabolism. It was shown that maintenance of the metabolic level in aging is very important for the life prolongation. PMID- 1430579 TI - [The bilateral asymmetry of the number of bristles in Drosophila occurring under the influence of methotrexate]. AB - The data are analyzed on the bilateral asymmetry of the number of dorsal and scutellar chaeta observed under the action of methotrexate in Drosophila of wild strain. It was shown that the incidence of asymmetric specimens induced by methotrexate was abruptly increased as compared to the control. The asymmetry was found to have a statistically significant trend to left side both of the control and the variants of treatment. There was no sex difference revealed between targets of the asymmetry. PMID- 1430578 TI - [A symmetrical approach to the analysis of cardiocyte electrical and contractile activity]. AB - Based on the systemic symmetrical approach, experimentally determined parameters of action potential and contractile response of frog myocardial strip were analyzed prior to and after the administration of several physiologically active drugs (caffeine, neoepinephrine, nembutal, ouabain) into the perfusate. It was shown that the satisfactory functional state of preparation was characterized by an interrelation between parameters in the form of a harmonic proportion with relatively constant coefficient. When the functional state of subject is affected by a physiologically active substance, the interrelation between the parameters is considerably changed. Based on the analysis of the data of literature, it was found that the interrelation between temporary parameters of action potential in various structures from human heart has the form of a harmonic proportion with a constant coefficient close to the invariant of "Gold Wurf" proportion. The similarity is underlined of principles of cardiac function temporary arrangement at levels of cell, organ and organism. PMID- 1430576 TI - [The effect of chemotherapy on the total unsaturation and composition of plasma phospholipids and erythrocytes in patients with disseminated breast cancer]. AB - The total unsaturation and composition of blood phospholipids were studied in patients with disseminated breast cancer prior to and after chemotherapy. It was shown that the level of double bonds in blood lipids was quite definitely related to the effect of treatment and may have an independent prognostic significance. A correlation was established between the survival of patients and the character of changes in the level of double bonds after chemotherapy. The treatment did not influence the relative content of different fractions and the oxidizability of plasma phospholipids and erythrocytes. PMID- 1430580 TI - [The technology for isolating the avian myeloblastosis virus in high titers from leukosis-free chicks]. AB - In order to enhance the outcome of high-quality reverse transcriptase enzyme, an efficient biotechnology was developed of accumulating and isolating the avian myeloblastosis virus (AMV) in high titres from blood plasma of leukosis-free chickens. When commercial chickens are infected in most sensitive one-day age, the virus titre does not exceed the value of 10(12) particles per 1 ml of plasma. We used 3-4-day old leukosis free chickens and achieved a stable average titre of the virus of 5.10(12) particles/ml due to adaptation of the virus to such chickens and their selection for a high sensitivity to AMV. PMID- 1430581 TI - Breathing pattern analysis. PMID- 1430582 TI - Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. AB - We studied, in 40 children (mean age: 52 months) with severe infectious purpura, the relationships between protein C (PC) and protein S (PS) levels, and shock, disseminated intravascular coagulation (DIC) and outcome. We determined, on admission, PC antigen (ELISA) and activity (chromogenic test), and total PS (ELISA). Results were expressed as % of normal adult values. Statistical analysis was performed with SAS. Thirty children were in shock, 20 had DIC. All children with DIC, and 10 without DIC were in shock. Of 20 children who were in shock and had DIC, 7 died and 3 had an amputation. PC antigen was significantly decreased in shock children (p less than 0.05), in children with DIC (p less than 0.0005), and in non-survivors (p less than 0.05). PC activity was significantly decreased in shock children (p less than 0.05), in children with DIC (p less than 0.0005), and in non-survivors (p less than 0.005). Total PS was not decreased in shock children, but was significantly decreased in children with DIC (p less than 0.005), and in non-survivors (p less than 0.005). We conclude that PC and PS levels were decreased in our children, and that PC levels were significantly decreased in the presence of shock, DIC, and fatal outcome. PC and antithrombin III (AT III) supplementation, should be evaluated in children with severe infectious purpura with shock and DIC. PMID- 1430583 TI - Oxygen consumption after cardiac surgery--a comparison between calculation by Fick's principle and measurement by indirect calorimetry. AB - Oxygen consumption calculated by Fick's principle (cVO2) was compared to oxygen consumption measured (mVO2) by indirect calorimetry (Deltatrac Metabolic Computer) in 10 patients in the post-operative period after cardiac surgery. For 50 pairs of measurements the mean difference (mVO2-cVO2) was 34 +/- 27 ml/min.m2. The limits of agreement were -20 ml/min.m2 to 88 ml/min.m2. These results showed that cVO2 and mVO2 were not interchangeable in this study. PMID- 1430584 TI - Uncertain relevance of gastric colonization in the seriously ill. AB - We have studied the temporal relationship for the same micro-organisms between gastric colonization and both nasopharyngeal colonization and major clinical infections in 100 consecutive, long-stay, intensive care patients. 67% of patients developed positive gastric cultures, mainly with aerobic Gram-negative bacilli and C. albicans; 33% developed positive nasopharyngeal cultures with similar organisms, but in only 8% was the same organism previously cultured from the stomach; 48% of patients developed infections, mainly respiratory, but commonly with different organisms. The presence of a positive gastric culture was not associated with gastric pH, bleeding, severity of illness, or mortality. The results fail to confirm that an ascending migration of organisms from the stomach is.frequent or that there is a relationship between gastric colonization and clinical infections. Firm therapeutic recommendation in these areas may be premature. PMID- 1430585 TI - Role of selective digestive decontamination (SDD) in the prevention of nosocomial pneumonia (NP): is gastric decontamination necessary? AB - In the course of a prospective selective digestive decontamination (SDD) trial to prevent nosocomial pneumonia (NP) during mechanical ventilation (MV), we carried out serial cultures of gastric aspirate to assess the importance of gastric colonization for potential respiratory pathogens and its relationship to the simultaneous gastric pH, to whether the patients were receiving Sucralfate or Ranitidine and to the nutritional biochemical parameters. If NP developed, a bronchial sample was taken by fibreoptic bronchoscopy to determine the causal organisms and its relationship to the previous gastric isolated. Results show: 1) Increase in aerobic Gram negative bacilli colonization during hospitalization. 2) Direct relationship between colonization level and gastric pH. 3) Greater pH in ranitidine vs sucralfate group. 4) Low incidence of NP (11%), the majority of these (66%) being early. 5) No bacteriological correlation between gastric colonization and aetiological agents of NP. 6) Close relationship between pharyngeal colonization and causative germs of pulmonary infection (40%). PMID- 1430586 TI - Reestimation of the effects of inorganic phosphates on the equilibrium between oxygen and hemoglobin. AB - In a previous paper, published in this journal, we showed that the data obtained in patients with severe ketoacidosis suggest that inorganic phosphates (K2HPO4) can increase their P50 and therefore enhance tissue oxygenation without concomitant alteration of the 2,3 diphosphoglycerate (DPG). In order to test the hypothesis that K2HPO4 could influence the oxyhemoglobin dissociation curve (ODC) by a mecanism which was not DPG mediated we have measured the total ODC on whole blood with and without addition of 13-80 mmol/l of inorganic phosphates. On average, the level of DPG remained unchanged when the P50 with K2HPO4 was significantly higher (p greater than 0.001) (P50 = 29.9 +/- 3.7 mmHg) than when phosphates were not administered (P50 = 25.5 +/- 2.8 mmHg). The relationship between P50 (mmHg) and K2HPO4 (= X mmol/l) was delta P50 = -2.97 10(-3)(X)2 +0.26(X)-0.42 (r = 0.78). Seeing that phosphates have an immediate action on the ODC, we calculated in our ketoacidosis patients, the relationship between the P50, the inorganic phosphates (P(i) in mg%) and the DPG in mumol/gHb. Both factors exert a highly significant effect (p less than 0.001) on the P50, according to the following equation: P50 = 0.35 DPG +0.26 P(i) + 18.92 (r = 0.73). Our data are important in two points. First it is useful to add inorganic phosphates to the treatment of patients with severe ketoacidosis in order to enhance their tissue oxygenation. Second they recall that the ODC is not only determined by the classical effects of temperature, pH and DPG but also by inorganic anions, like phosphates as described by Benesh and Benesh in their pioneering work. PMID- 1430587 TI - Tidal volume, breathing frequency, and oxygen consumption at different pressure support levels in the early stage of weaning in patients without chronic obstructive pulmonary disease. AB - The objective of this study was to evaluate the influence of different PSV levels on VT, F, VO2 in the early weaning phase of patients without chronic obstructive pulmonary disease. These parameters were tested for the predictive power for the success of the weaning. Patients on SIMV were studied during the first weaning attempt with PSV. Depending on their ventilatory support demands after 24 h they were divided into responders (patients breathing on CPAP) and nonresponders (patients being on a more invasive ventilatory mode). 14 ICU patients without pre existing pulmonary disease being ventilated for at least 3 days entered the study. 2 of them could be studied a second time after failing the first weaning attempt. Beside the level of ventilatory support no other changes (drugs, nutrition) were allowed. VO2, VT, F were measured by a computer controlled, metabolic unit connected to the expiratory port of a Siemens Servo Ventilator. In addition, airway pressures, arterial pressure and heart rate were recorded. The measurements were performed at PSV of 5, 10 and 20 cmH2O. Arterial blood-gases were drawn at the end of each 60 min lasting PS period. Responders and nonresponders could be separated by the response of VO2, VT and F to a change in PS 10 to PS 20 cmH2O. Patients who significantly increased VT and significantly decreased F did not fulfil our weaning criteria. Our responders did not show a significant change in these two parameters, but a significant increase in VO2 at PS 20 cmH2O could be observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430588 TI - Fat emulsions containing medium chain triglycerides in patients with sepsis syndrome: effects on pulmonary hemodynamics and gas exchange. AB - Fat emulsions containing medium chain triglycerides (MCT) have recently been introduced into clinical practice as a component of total parenteral nutrition. Since several authors reported increased pulmonary artery pressure and impaired gas exchange during intravenous (i.v.) fat use, in particular in septic patients, we studied the pulmonary hemodynamic and gas exchange effects of i.v. fat containing MCT and long chain triglycerides (LCT) in patients with sepsis syndrome. As the effects of fat emulsions have been attributed to increased formation of prostanoids, the production of thromboxane A2 and prostacyclin was investigated by the determination of urinary thromboxane B2 and 6-keto prostaglandin F2 alpha, respectively. The i.v. fat use did not induce any alterations in pulmonary hemodynamics and gas exchange, the distribution of ventilation and perfusion nor urinary prostaglandin content. We conclude that fat emulsions containing MCT induce little alterations in pulmonary hemodynamics and gas exchange. This result is probably due to reduced prostaglandin formation because fat emulsions containing MCT provide less prostaglandin precursors than pure LCT emulsions. PMID- 1430589 TI - High volume hemofiltration improves right ventricular function in endotoxin induced shock in the pig. AB - This study assessed the influence of continuous high volume hemofiltration on right ventricular function of pigs with endotoxin induced shock. Eighteen anesthetized and ventilated pigs were studied for 240 min after the start of infusion of 0.5 mg/kg endotoxin over 30 min. Right ventricular ejection fraction (RVEF) was measured by rapid response thermodilution technique. After endotoxin infusion, the pigs were randomly divided into 3 groups: group 1 as a control group, receiving endotoxin only, group 2 to observe the effects of zero balance high volume veno-venous hemofiltration with removal of ultrafiltrate at a rate of 6000 ml/h, and group 3 to evaluate the effect of the extracorporeal circuit itself on RVEF. The decline of RVEF in group 2 was less than in group 1 (0.04 +/- 0.02 vs 0.21 +/- 0.03 (mean +/- SEM); p less than 0.001). The decline of RVEF in group 3 (0.24 +/- 0.02) was more pronounced than that in group 1 (p less than 0.05). The differences in the course of RVEF between group 1 and group 2 could not be explained by differences in heart rate, preload or afterload. Cardiac output and mean arterial pressure were significantly higher in group 2 than in group 1 (p less than 0.01). It is concluded that in this model, high volume hemofiltration improves RVEF and cardiac performance by removal of vasoactive mediators, responsible for myocardial depression. PMID- 1430590 TI - Treatment of severe tetanus by intrathecal injections of baclofen without artificial ventilation. AB - A study was conducted to evaluate repeated intrathecal injections of baclofen, without artificial ventilation, in the treatment of severe tetanus. Ten patients, 5 men and 5 women, with a mean age of 34 +/- 7 years, were included in the study. The dose of baclofen injected was 1000 micrograms between the ages of 16 and 55 years, 800 micrograms over the age of 55 years and 500 micrograms under the age of 16 years. The efficacy was assessed on the basis of the resolution of contractures and paroxysms and the initial dose was reinjected prior to the reappearance of these symptoms. Treatment was discontinued in the case of central nervous system depression or inefficacy. The first injection was effective in 9 cases for 24-48 h. The haemodynamic safety was always good. Five patients developed central depression with coma and respiratory depression, requiring artificial ventilation in 3 cases and reversed by flumazenil in 2 cases. Five patients were treated exclusively with baclofen with 4 cures. Five patients had to be ventilated with only one cure. This study confirms earlier studies concerning the efficacy of intrathecal baclofen in tetanus. However, the frequency of episodes of respiratory depression prevents the recommendation of repeated injections when respiratory intensive care facilities are not available. PMID- 1430591 TI - Diagnosis of gallbladder perforation in acute acalculous cholecystitis in critically ill patients. AB - In the presence of ascites ultrasound is not appropriate to distinguish between gallbladder perforation and acute acalculous cholecystitis. However, the correct and early diagnosis of gallbladder perforation is important for the treatment and prognosis. We report 4 critically ill patients with ascites. All patients had evidence of gallbladder perforation by ultrasound and underwent cholecystectomy: 2 patients had gallbladder perforation, but 2 had acalculous cholecystitis without perforation. Markedly elevated serum alkaline phosphatase was the only discriminating finding indicating gallbladder perforation. PMID- 1430592 TI - Severe acute myocardial infarction during a staphylococcal septicemia with meningoencephalitis. A possible contraindication to thrombolytic treatment. AB - We report the first case of lethal intracranial haemorrhage complicating a treatment by rt-PA in a patient presenting with a simultaneous staphylococcal septicemia with meningoencephalitis and an acute myocardial infarction with cardiogenic shock. The presence of microvascular lesions in the central nervous system seems to be important risk factor for intracranial haemorrhage and we recommend extreme caution in the use of thrombolytic treatment in septicemic patients with acute myocardial infarction, particularly when neurological symptoms are present. PMID- 1430593 TI - Transient non-cardiogenic pulmonary edema following massive ingestion of ethylene glycol butyl ether. AB - A case of acute poisoning with ethylene glycol butyl ether (EGBE) is reported in a chronic alcohol abuser. On admission the 53-year-old patient was comatose with metabolic acidosis, shock, and noncardiogenic pulmonary edema confirmed by haemodynamic study. Following supportive treatment and haemodialysis the outcome was favorable. The relationship between respiratory failure and EGBE is examined. PMID- 1430594 TI - Disturbance of cerebral autoregulation after global ischemia and the stabilizing role of adenosine. PMID- 1430595 TI - Can purgation therapy be an adjunct to SDD? PMID- 1430596 TI - Bradycardias after tracheal disconnection. PMID- 1430597 TI - Who was Morton Prince? AB - Morton Prince, a Boston neurologist, founded the Journal of Abnormal Psychology in 1906 as an outlet especially for those who took a psychogenic view of neurotic disorders. Through experiments with hypnotism, he added appreciably to knowledge of subconscious and coconscious mental processes; The Dissociation of a Personality (Prince, 1905) still ranks as a classic. He early saw that studying normal people in the depth and detail with which one studied patients could make significant contributions to our whole understanding of human nature. Before his death he established and briefly directed the Harvard Psychological Clinic, devising the research environment out of which presently sprang major contributions to the study of personality. PMID- 1430598 TI - Morton Prince on anxiety disorders: intellectual antecedents of the cognitive approach to panic? PMID- 1430599 TI - A clinical study of a case of phobia. 1912. PMID- 1430600 TI - Relation between self-reported affect and drug urges and cravings in continuing and withdrawing smokers. AB - In 2 experiments we investigated the effects of withdrawal and stress on the affective correlates of urges to smoke. In both, habitual cigarette smokers were divided into continuing and withdrawing smoker groups. In the 1st study, 44 adults reported current mood, urge, and expectations over a 24-hr period. In the 2nd, a controlled laboratory study, urge, affect, and physiological data were obtained from continuing and withdrawing groups (N = 64) exposed to high- or low stress conditions. Urges among withdrawing smokers were positively associated with negative affect and negatively associated with positive affect; continuing smokers reported urges that were directly associated with positive affect and unrelated to negative affect. Stress and withdrawal produced urge self-reports that were related to negative affect. Moreover, subjects who smoked after exposure to withdrawal and stress reported greater pleasure and arousal than did other subjects. PMID- 1430601 TI - Delay of gratification in psychopathic and nonpsychopathic offenders. AB - Delay of gratification is a prototypical measure of self-control that merits systematic investigation in psychopaths. White male prisoners were provided with repeated opportunities to select an immediate response with uncertain reward or a delayed response with a higher rate of reward under one of three incentive conditions. Psychopaths' performance depended on their level of trait anxiety and incentive condition: Whereas low-anxious psychopaths were relatively unwilling to delay when omission of expected rewards also incurred monetary punishments, they displayed relatively superior performance when the task involved rewards only. Findings complement those for passive avoidance learning in psychopaths and suggest that inhibitory self-control in low-anxious psychopaths is somewhat impaired under conditions involving a combination of monetary rewards and punishments. PMID- 1430602 TI - Depressed patients with dysfunctional families: description and course of illness. AB - Sixty-eight depressed patients were subdivided according to their family's level of family functioning into functional and dysfunctional groups. Patients from dysfunctional families did not differ from those from functional families on measures of severity of depression, chronicity of depression, depression subtypes, other nonaffective psychiatric diagnoses, history of depression, or neuroendocrine functioning. Patients from dysfunctional families did have significantly higher levels of neuroticism. A 12-month follow-up of these patients indicated that depressed patients with dysfunctional families had a significantly poorer course of illness, as manifested by higher levels of depression, lower levels of overall adjustment, and a lower proportion of recovered patients. Thus, impaired family functioning appears to be an important prognostic factor in major depression. PMID- 1430603 TI - Sequential analysis of marital interactions involving alcoholic, depressed, and nondistressed men. AB - This study was based on the investigators' earlier work on alcoholism and the family and involved a comprehensive assessment of sequential patterns associated with the marital interactions of alcoholic, depressed, and nondistressed men. A total of 131 couples were assessed in a laboratory-based discussion of personally relevant problems. Videotaped observations were conducted during drinking and nondrinking sessions and were subsequently coded according to the Marital Interaction Coding System. Depressed couples were most distinguishable in terms of unique antecedent-consequent patterns, whereas alcoholic and nondistressed control couples were similar to one another and different from depressed couples. Results are discussed in regard to the extant literature on interpersonal theories of depression and alcoholism and in regard to future research needs. PMID- 1430604 TI - Expert judgments of hypnosis from subjective state reports. AB - Suggestibility was assessed in 60 college students after a traditional hypnotic induction, an alert induction, progressive relaxation training, or instruction in goal-directed imagery. Responsiveness to suggestion did not differ between groups. Subjects also generated open-ended reports of their states of awareness and of their experience of 3 hypnotic suggestions. A sample of these reports from 24 moderately to highly suggestible subjects were evaluated by 18 experts in the field of hypnosis. Expert ratings of subjects' open-ended reports indicated that (a) traditional hypnotic inductions produce a state of consciousness that is indistinguishable from nonhypnotic relaxation training, (b) the subjective experience of hypnotic suggestions after imagination training is indistinguishable from that after hypnotic inductions, and (c) suggestibility is unrelated to state of consciousness as assessed by experts. PMID- 1430605 TI - Transient positive and negative experiences accompanying stage hypnosis. AB - Frequency of positive and negative experiences accompanying stage hypnosis was assessed in follow-up interviews with 22 participants of university-sponsored performances. Most subjects described their experience positively (relaxing, interesting, exciting, satisfying, illuminating, and pleasurable), but some described it negatively (confusing, silly, annoying, and frightening). Five subjects (22.7%) reported partial or complete amnesia; all were highly responsive to the stage hypnosis suggestions. One subject was completely unable to breach amnesia and felt annoyed and frightened. Five subjects (22.7%) believed the hypnotist had control over their behavior. Participants (n = 15) tested subsequently on the Stanford Hypnotic Susceptibility Scale, Form C (Weitzenhoffer & Hilgard, 1962) were mostly moderately to highly hypnotizable (M = 7.07), and the scores correlated significantly (r = .68) with the percentage of passed stage hypnosis suggestions. PMID- 1430606 TI - Relationship between dietary restraint, energy intake, physical activity, and body weight: a prospective analysis. AB - Dietary, activity, and body weight differences in high- and low-restrained eaters and the independent impact of dietary restraint on body weight change were evaluated in 287 adults (141 men, 146 women) followed over a 1-year period. Analyses of measures of energy intake, physical activity, and dietary restraint indicated that high-restrained eaters did not differ in physical activity compared to low-restrained eaters at baseline but were ingesting significantly fewer kcal/lb and a higher percentage of the diet from fat. Body mass was significantly greater in both high-restrained men and high-restrained women than in their low-restrained counterparts. Regression modeling procedures revealed that weight and body mass at baseline were related to weight gain in men. In contrast, weight gain in women was predicted by baseline weight and higher restraint scores. These results indicate that dietary restraint is associated with weight gain in women but not in men. PMID- 1430607 TI - Comparison of bulimics, obese binge eaters, social phobics, and individuals with panic disorder on comorbidity across DSM-III-R anxiety disorders. AB - Eighty-two women, presenting as normal-weight bulimics, obese binge eaters, social phobics, and individuals with panic disorder, were compared on anxiety, depression, and substance abuse. All were administered the Anxiety Disorder Interview Schedule-Revised and completed the Michigan Alcohol Screening Test, Drug Abuse Screening Test, and Self-Consciousness Scale. A striking proportion of eating disorder subjects were comorbid for one or more anxiety disorders, the most frequent diagnoses being generalized anxiety disorder and social phobia. The results suggest that the place of anxiety in bulimia nervosa goes beyond that discussed within the context of the anxiety reduction model. Conflicting comorbidity findings among this and prior investigations are noted, however, and discussed in terms of the issue of differential diagnosis between eating and anxiety disorders. PMID- 1430608 TI - Attentional cues in chronic schizophrenia: abnormal disengagement of attention. AB - Posner's (1980) reaction time (RT) paradigm was used to examine the engagement and disengagement operations of visual selective attention in patients with schizophrenia. In the 1st experiment, 14 medicated, chronic schizophrenic subjects (diagnosed by criteria of the Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association, 1987) and 15 age-matched normal control subjects made a speeded response to a target preceded by a valid, an invalid, or no cue. Control subjects showed the expected advantage and disadvantage in RT for valid and invalid cues, which suggests intact engagement and disengagement operations. For schizophrenic patients, valid cues also enhanced RT, but invalid cues did not slow RT. Similar results were found in the 2nd experiment. The failure of unpredictable, invalid cues to inhibit RT in chronic schizophrenia may be related to an abnormality in the disengagement operation of selective attention. PMID- 1430609 TI - Influence of rapport on hypnotically induced pseudomemory. AB - Three studies examined the influence of rapport on pseudomemory. Study 1 tested eight groups of 22 subjects in a 2 (level of susceptibility: high, low) x 2 (state instruction: hypnosis, waking) x 2 (rapport: present, reduced) design, rapport being inhibited by the hypnotist criticizing subjects' performance. Pseudomemory was tested by a second experimenter who also criticized subjects. Study 2 varied level of susceptibility and rapport for 88 hypnotically instructed subjects where criticism was offered only by the second experimenter. Study 3 analyzed effects among 44 highly susceptible hypnotic subjects where the second experimenter refrained from criticizing subjects. Data indicated a significant association between rapport with the hypnotist and pseudomemory in cued recall, strength of pseudomemory being appreciably lowered when negative hypnotist rapport was reinforced by the person testing pseudomemory. PMID- 1430610 TI - Importance of shared genes and shared environments for symptoms of depression in older adults. AB - The Center for Epidemiologic Studies-Depression scale was administered to 68 identical and 161 fraternal twin pairs reared apart and 114 identical and 138 fraternal pairs reared together to ascertain relative genetic and environmental contributions to individual differences in self-reported depressive symptoms. Intraclass correlations and model fitting indicated that genetic influences explained 16% of the variance in total depression scores and 19% for the Psychomotor Retardation and Somatic Complaints subscale, but heritability was minimal for the Depressed Mood and Well-Being subscales. Influence of family rearing context played a substantial role in explaining twin similarity, whereas unique life experiences accounted for the greatest proportion of variance. Significant age group differences were observed, with heritability greater in twins of 60 years of age or older than in twins under 60, especially for Psychomotor Retardation. PMID- 1430612 TI - Dissociative experiences, psychopathology and adjustment, and child and adolescent maltreatment in female college students. AB - Thirty-three female college students who scored in the upper 15% on the Dissociative Experiences Scale (DES) were compared with 33 female students who scored below the mean on the DES on measures of psychopathology (Symptom Checklist-90), college adjustment (Student Adaptation to College Questionnaire), and child and adolescent maltreatment. Compared with controls, high-DES subjects reported more psychopathology, poorer college adjustment, and a greater extent of psychological, physical, and sexual maltreatment. On the basis of the Dissociative Disorders Interview Schedule, 2 high-DES subjects but none of the control subjects met criteria for a dissociative disorder (i.e., multiple personality and psychogenic amnesia). Despite the sensitivity of the DES, 8 subjects who scored in the upper 2% of the population on the DES failed to meet criteria for a dissociative disorder. PMID- 1430611 TI - Monaural and binaural story recall by schizophrenic subjects. AB - P. Green and other investigators have reported that schizophrenic Ss have poorer recall of stories presented to both ears than to the single best ear (binaural deficit) and poorer recall of stories presented to the left ear than to the right ear (monaural asymmetry) than do normal control Ss. These studies are plagued by potential methodological problems, including differences in overall accuracy, which artifactually affect the difference scores, and scoring methods that are vulnerable to systematic bias. In this study, scores of schizophrenic, bipolar, and normal control Ss on the Auditory Comprehension Test were compared. Scoring bias was avoided by the use of blind scoring and a revised scoring manual, and artifactual effects of accuracy were considered in interpreting the results. Contrary to previous findings, the groups did not differ on either monaural asymmetry or binaural deficit. PMID- 1430613 TI - Covariation detection in treated and untreated spider phobics. AB - Twenty treated and 18 untreated spider phobics were exposed to a series of 72 slides. Three different categories of slides were used: phobia-relevant slides (spiders), alternative fear-relevant slides (weapons), and neutral slides (flowers). Slides were randomly paired with either a shock, a tone, or nothing at all. Despite the absence of a systematic correlation between slides and outcomes, untreated phobics strongly overestimated the covariation between spider slides and shock. Treated phobics did not show a covariation bias, suggesting that such bias can be modulated by behavioral treatment. In addition, untreated subjects were more confident about their contingency estimates than were treated subjects. The present results fit with earlier studies. PMID- 1430614 TI - Discrepancy between self- and observer ratings of performance in social phobics. AB - Twenty-eight subjects meeting Diagnostic and Statistical Manual of Mental Disorders (rev. 3rd ed.; American Psychiatric Association, 1987) criteria for social phobia and without a comorbid affective disorder and 33 nonclinical controls were asked to present a brief, impromptu speech to a small audience. Speakers themselves, as well as members of the audience, rated each speaker on a public speaking questionnaire that included both specific items (e.g., voice shook) and global items (e.g., appeared confident). For global items, no significant difference was indicated between the two groups on observers' ratings of public speaking performance. However, social phobics rated their own performance worse than did nonclinical controls, and there was a significantly greater discrepancy between self and other ratings for social phobics than controls. Fear of negative evaluation was the only significant predictor of the self-other discrepancy on global items. PMID- 1430616 TI - Research and development in nursing. PMID- 1430615 TI - Medication status of participants in psychopathology research: selective review of current reporting practices. AB - The majority of Ss included in studies of psychopathology are typically receiving psychoactive medication. In view of concerns regarding the confounding effects of psychoactive medication, it appears that researchers should provide information regarding at least the drug status of the Ss studied. A review of the articles on adult psychopathology that appeared in the Journal of Abnormal Psychology during a 5-year period, however, revealed that nearly 50% of reports on Ss presumably receiving psychoactive medications failed to specify the medication status of those Ss. Few studies (15%) provided adequate information regarding the types and dosages of psychoactive drugs received by the Ss. It is argued that researchers should provide a full report of the psychoactive drugs received by research participants and, when participants are unmedicated, to indicate the reasons for drug-free status. PMID- 1430617 TI - The Gulf War: reaction and action in institutions for the aged in Israel. AB - In order to learn how geriatric centres were coping during the Gulf War (1991), questionnaires were distributed to 116 unit head nurses in 16 institutions in Israel. Additional information was obtained from the directors of nursing and national supervisors in a meeting 3 1/2 months after the cease-fire. Questions focused on organization of work, behaviour of staff, patients and their families, main problems, solutions and recommendations. Data showed a very high level of commitment by staff, flexibility, initiative and creativity in meeting the emotional, physical and safety needs of the aged. Stress level was highest in the 'Scud' areas and among the aged who are mentally alert. Families visited less but increased contact by telephone. Management was supportive with guidance, transport, child care facilities, etc. They also provided beds and food for spouses of the aged residents. Major problems related to safety measures (sealing rooms, moving patients during attacks), physical exhaustion and emotional stress of staff, and reorganization of care programmes. Recommendations included development of a master plan for non-conventional attacks, preparation of buildings with structural improvements, recruitment and training of volunteers, clarification of roles of staff and education for them. PMID- 1430618 TI - The young pioneers: first baccalaureate nursing students in the People's Republic of China. AB - Nursing in the People's Republic of China, like elsewhere, has undergone monumental changes during the 20th century. This paper focuses on one of those changes by examining the professional socialization process of the first class from the first baccalaureate in nursing (BSN) programme in China since 1952. These data from this first BSN class are part of a larger study on professional socialization in which data were collected from four of the recently established 11 BSN programmes in China. To put these data into a historical context, some highlights of Chinese nursing history are noted. These will help us to understand the present-day situation in this the world's most populous nation. PMID- 1430619 TI - Diagnostic reasoning among second-year nursing students. AB - This paper reports on a study investigating the relationship of nursing students' approaches to learning and processing of information, science content knowledge, ability in interpreting and organizing clinical data (nursing assessment), and logical reasoning ability with the accuracy and quality of the nursing diagnosis made in a simulated diagnostic reasoning task. One hundred and sixty-nine second year pre-service nursing students participated in the study. Results of path analyses indicated a set of pathways from surface approach to low-quality nursing diagnosis that reflected less competent diagnostic reasoning; and a second set from deep/achieving approach through content knowledge and logical reasoning to higher-quality nursing diagnosis that reflected more competent diagnostic reasoning. The implications of these findings for nurse education are discussed. PMID- 1430620 TI - The Case Management Model: an innovative approach to the delivery of patient care. AB - Because of trends in the health care environment, hospitals are restructuring to innovative patient care delivery systems. The Case Management Model, with its emphasis on quality patient care and cost containment, is gaining widespread recognition throughout Canada and the United States. In this paper, the Case Management Model is described in relation to nursing practice. PMID- 1430621 TI - Good nursing practice as perceived by clients: a starting point for the development of professional nursing. AB - This paper presents clients' experiences of health care and nursing services in the Finnish primary health care and hospital system. These are described to find evaluation criteria for good nursing care and to point out challenges for development of the nursing profession. PMID- 1430622 TI - Witnessing family violence: the children's experience. AB - A phenomenological study was conducted in order to describe the experience of children as they accompany their mothers who are leaving abusive relationships. Thirteen children were interviewed. The children describe their experience as having three components: living with violence, living in transition and living with Mom. Themes within these components are identified, and implications for nursing practice are discussed. PMID- 1430624 TI - Cardiovascular disease prevention: knowledge and attitudes of graduate nursing students. AB - Graduate nursing students were surveyed to determine the knowledge and attitudes of cardiovascular disease prevention. Questionnaires were self-administered to first-year graduate nursing students (n = 50) in a school of nursing prior to and following a physiology course with cardiovascular disease prevention content. In general, the results demonstrated that the respondents were least knowledgeable regarding the prevalence of smoking, the gender differences in high-density lipoprotein (HDL)-cholesterol levels, the influence of body weight on lipids and the recommended percentages of calories from dietary fat. A significant improvement in knowledge was noted after the course. Positive attitudes regarding the importance of cardiovascular disease prevention and the partnership between patients and clinicians necessary to manage risk were identified. These attitudes did not change significantly following the course. These results indicate that graduate education which emphasizes cardiovascular disease prevention increases knowledge. Coupled with positive attitudes and healthy personal lifestyle behaviours, knowledge of cardiovascular disease prevention may enhance the ability of nurses to integrate preventive standards into clinical practice and ultimately decrease the risk of cardiovascular disease. PMID- 1430623 TI - The role of the nurse in high-quality patient care: a review of the literature. AB - A review of the literature reveals a range of the nurse's subroles within the service of nursing. Competence in psychomotor, cognitive and affective skills is required for performance within each of these subroles to achieve the delivery of high-quality nursing care. PMID- 1430625 TI - Characteristics of effective nursing interventions in the management of challenging behaviour. AB - A combination of semi-structured interviews and participant observation were used in order to investigate the interventions used by psychiatric nurses when faced with challenging behaviour. The study described 10 such categories of effective interventions: confirming messages, personal control, staff honesty, providing face-saving alternatives, setting limits, use of structure, facilitating expression, monitoring, timing and calming, and non-verbal skills. The report concludes by suggesting that these categories can be used to provide a structure for the analysis of critical incidents from a nursing perspective. PMID- 1430626 TI - Participation of informal caregivers in the hospital care of elderly patients and their evaluations of the care given: pilot study in three different hospitals. AB - This action research is an ongoing study which will last from 1991 to 1993. The main purpose of the study is to increase the participation of informal caregivers in the hospital care of elderly patients without decreasing the quality of care. The data reported here are from a pilot study. This study had three aims: (a) to test reliability and validity of the measure used, (b) to investigate the current participation of informal caregivers in the hospital care of elderly patients (aged over 75), and (c) to evaluate and compare the quality of care from both the patients' and the informal caregivers' point of view in three different hospitals. The measure of quality of care was developed on the basis of need theories, mainly those of Maslow and Alderfer. Patients and caregivers were also asked to rate the participation of the caregivers in the hospital care of elderly patients. Participation consisted of 18 activities of daily living. The pilot test with 18 elderly hospital patients and seven family members or significant others showed differences between the two groups in perception of care received. Statistically significant differences (P < 0.001) were found in the following categories: mainly social needs, psychic and spiritual needs and totals. The results supported earlier findings that elderly patients are satisfied with and do not criticize their care. The younger generation (i.e. their children) is more demanding and has precise perceptions about the care given. Relatives could be used more in planning, evaluation and even implementation of care; however, their current participation in patient hospital care is minimal. PMID- 1430627 TI - Confidence as a factor in chronic illness care. AB - Confidence is generally regarded as a positive quality which enhances personal coping and success. For those who are chronically ill and face a life of uncertainty, confidence becomes especially important. In a recent qualitative study examining chronically ill patients' perceptions of nursing care, confidence was found to be the grand essence which tied together all the informants' experiences with good nursing care. The informants entered the hospital with the expectation that the nurses would and could look after them. Observing and receiving good nursing care reinforced this confidence. In addition to this, the informants referred to confidence that was developed by the interest and value the nurses placed on the patient as an individual. Showing an interest in the patient as an individual gave the patient confidence in self-worth and in personal coping ability. These two sources of confidence combined to give the informants confidence in their futures. In the nursing literature the exploration of the concept of confidence is minimal. This paper discusses confidence as a factor in the care of the chronically ill using data from the study for illustration. PMID- 1430628 TI - Skin problems beneath the breasts of in-patients: the knowledge, opinions and practice of nurses. AB - A survey of knowledge and nursing practice in relation to sub-mammary skin problems was conducted among ward sisters and primary nurses in one district health authority. Respondents identified a number of characteristics as predisposing factors, with obesity and poor hygiene being mentioned most frequently. A very wide selection of nursing interventions was recommended, with nurses who mentioned pharmacologically active topical preparations reporting a significantly greater number of recurrences among patients than those who relied on less sophisticated regimes. Nurses expressed a variety of opinions about the effect that this condition has on patients, ranging from no effect at all to pain and discomfort. These findings highlight the lack of a coherent strategy for treating this problem and support the continuation of a research programme examining sub-mammary skin problems and the nursing response to them. PMID- 1430629 TI - Abbreviated instrument to measure hope: development and psychometric evaluation. AB - The purpose of this research was to develop and evaluate psychometrically an abbreviated instrument to assess hope in adults in clinical settings. The Herth Hope Index (HHI), a 12-item adapted version of the Herth Hope Scale (HHS), was tested with a convenience sample of 172 ill adults. Alpha coefficient was 0.97 with a 2-week test-retest reliability of 0.91. Criterion-related validity was established by correlating the HHI with the parent HHS (r = 0.92), the Existential Well-Being Scale (r = 0.84) and the Nowotny Hope Scale (r = 0.81). Divergent validity with the Hopelessness Scale was established (r = -0.73). Construct validity was supported through the factorial isolation of three factors: (a) temporality and future; (b) positive readiness and expectancy; (c) interconnectedness. These three factors accounted for 41% of the total variance in the measure. PMID- 1430631 TI - Nursing: the hands and heart of science. PMID- 1430630 TI - Nurses' attitudes toward patients with AIDS and AIDS-related risk factors. AB - Three variables were experimentally manipulated by simulation measurement using six vignettes in a completely randomized, partial hierarchical, experimental design: medical diagnosis (AIDS v. non-AIDS), sexual orientation (heterosexual v. homosexual) and intravenous drug-use history (IVDU v. non-IVDU). Following each vignette, the same Prejudicial Evaluation Scale (PES) and Social Interaction Scale (SIS) were used to measure nurses' attitudes toward patients and their willingness to interact with patients. Vignette questionnaires were randomly assigned to 360 acute-care nurses. Although sexual orientation was found not to influence PES and SIS scores, an AIDS medical diagnosis and a history of intravenous drug use were found to increase nurses' negative attitudes toward patients significantly and reduce their willingness to interact with patients. Study findings did not vary according to nurses' age, academic preparation or previous practice experience with patients with AIDS. PMID- 1430632 TI - Patients' experience of technology at the bedside: intravenous infusion control devices. AB - Within health care systems, rapid and pervasive technological development is occurring with significant ramifications for both nurses and patients. In order to determine the patient's perception of the experience of clinical equipment at the bedside, an exploratory study of 150 hospitalized patients was undertaken. For this study an item of electronic clinical 'hardware', the infusion control device, used increasingly by nurses, was selected as an exemplar of bedside nursing technology. A positive patient response to the equipment and its management was found. The majority of respondents understood the reasons for the equipment's use, were not disturbed greatly by the alarms, had few concerns about the equipment and would welcome further use. A majority felt that the care they received was more patient centred than technology centred. Several recommendations for nursing practice follow from these findings. PMID- 1430633 TI - A view of the phenomenon of caring in nursing practice. AB - Care is regularly used as a suffix to nursing, in such well-known phrases as 'total nursing care' and 'holistic nursing care'. While most care is provided by lay persons, there is little nursing research which focuses on the meaning of care, particularly in relation to the United Kingdom. This small-scale study investigates the meaning of care from the experience of six practising staff nurses in a British hospital and leads to a view of this phenomenon. Phenomenology was the chosen methodology, which facilitated the emergence of an essential structure of caring which incorporated four major categories described as 'being supportive', 'communicating', 'pressure' and 'caring ability'. It is suggested that, through gaining perspectives to enhance our understanding of the meaning of care, it will ultimately develop our understanding of nursing itself. PMID- 1430634 TI - Health promotion in primary care: taking account of the patient's point of view. AB - Some of the difficulties of putting health promotion into practice are considered. It is argued that, in a health promotion intervention aimed at lifestyle change, three questions need to be considered concerning the image, the meaning and the implementation of the programme. PMID- 1430635 TI - 'Scripts' for dying at home--displayed in nurses', patients' and relatives' talk. AB - Perceptions and expectations reflecting what constitutes a 'good' death that seem to exist in Western societies are explored and compared with those presented by five symptom control team nurses at their home visits to 54 terminally ill cancer patients. These perceptions and expectations are termed 'scripts' for dying and are derived from the nurses', patients' and relatives' audio-recorded conversations over a 3-month period. The elements of the 'scripts' used were identified as: (a) control of physical symptoms, (b) acceptance of cancer and its prognosis, (c) preservation of hope and 'will to live', (d) mobility and 'fighting back', (e) enjoyment of life, (f) a peaceful death at home. How these components are determined from the conversations are presented and the responses of the patients to the nurses' 'scripts' are analysed. The dilemmas created by putting the 'scripts' into action for nurses, patients and relatives are discussed. PMID- 1430636 TI - Defining risk from the perspective of nurses in clinical roles. AB - Although the nursing literature suggests that nurses generally avoid risk, their willingness and ability to take risk are fundamental to their professional advancement, job satisfaction and patient advocacy. The definition of risk as it pertains in clinical practice, however, may not be synonymous with risk as defined in other fields. This study defines risk in nursing from the perspective of three registered nurses in clinical roles. Grounded theory methodology indicated that 11 risk categories comprised six core concepts. The latter formed the basis for the following: risk in clinical nursing practice is defined by uncomfortable and typically unavoidable role-related situations characterized by high unpredictability and negative or hostile overtones, dependency on others, exceedingly high performance expectations from self and others, unpleasant emotions, and health threats that extend beyond working hours. Findings of this study refute the notion that nurses avoid risks. Risk, ever present in the nurse's clinical practice and environment, requires strategies to minimize its negative impact. PMID- 1430637 TI - Familial inflammatory bowel disease in a paediatric population. AB - Familial aspects of inflammatory bowel disease (IBD) were assessed as part of an age and sex matched case control study of 91 children with IBD and 131 controls. The prevalence of IBD in family members of the children was studied, the affected side (mother's side or father's side) of the family was documented and the type of inflammatory bowel disease was traced among relatives. Data were collected from children in out-patient clinics at a large urban tertiary-care facility. All family data were verified with the affected relatives and/or their physicians. The children with IBD (the cases) had significantly (P = 0.0000385) more IBD in their families than the controls. Among all children with IBD in their family, IBD was found significantly (P = 0.0073) more often on the mother's side of the family than on the father's side. Patterns of disease varied within families. A mixture of ulcerative colitis and Crohn's disease was found within families. The implications of the findings are discussed. Directions for prevention, screening, early intervention and further study are given. PMID- 1430638 TI - Giving and receiving: an empirically derived theory on health visiting practice. AB - The aim of this study was to uncover how experienced health visitors conceptualize and evaluate their health visiting work. The grounded theory approach to data collection and analysis was used to develop a beginning midrange substantive theory about health visiting practice. The beginning theory provides an explanation and understanding of how health visitors work with clients in the community during their day-to-day visiting practice. Data were gathered from 45 experienced health visitors from 13 health authorities in the north-west of England by means of the conversational interview. The basic psychosocial problem uncovered in the data was health visitors' need to provide a service and clients' need to fulfil personal needs and goals. The unifying theme of giving and receiving integrated the major categories into the key analytic framework in this study. This key psychosocial process was the pattern of interaction between health visitors and clients, in which both parties control the interactions by regulating what they offer and accept from each other. Each party both selectively 'gives' and 'receives' in order to manage the health visitor-client encounters. What gets offered and how the offer is received and acted on is a complex process involving many factors related to the health visitor, the client, and the context in which the interaction takes place. PMID- 1430639 TI - Anxiety, accuracy and reflection: the limits of professional development. AB - Reflection is a key concept in the development and maintenance of nursing expertise in theory and practice, yet commentators have rarely examined difficulties associated with it. This paper describes the role of reflection in nursing and relates it to information-processing accounts of human memory. The issues raised by the role of memory in mediating reflection are discussed, in the context of an examination of the importance of accuracy in reflection-on practice. It is argued that anxiety is of particular importance in mediating accurate reflection. Whilst it is concluded that reflection is inherently flawed, a range of tactics to enhance it are explored, with particular emphasis on anxiety reduction and reduction of the burden of the memory task. PMID- 1430640 TI - Mothers and daughters: a powerful spell. AB - An unanticipated finding of a small exploratory study of the health of never married women in old age is discussed. Focused conversational interviews yielded evidence of the potent effect the mother-daughter relationship had in a group of women who had lived for all their adult lives in the parental home. Usually mothers had outlived fathers, and when they finally died daughters lost someone to whom they had been very close and at the same time had to cope with living alone for the first time in their lives. Three case histories, illustrating both strong positive and negative aspects of mother-daughter relationships are reported, and the psychological and sociological literature is explored. Parallels are also drawn with biographical and autobiographical literature about this type of relationship, including that of Florence Nightingale and her mother. Finally, some implications for nurses are considered and the special support needs of these women at bereavement and in old age are highlighted. PMID- 1430642 TI - Nursing models in a special hospital: cybernetics, hyperreality and beyond. AB - Two emerging themes that resulted from research carried out in a special hospital on the use of nursing models are identified. The first theme to emerge was the tendency of the subjects to perceive the models as concrete entities thus undergoing a process of reification. The second theme identified was the adherence to the models outside the contextual nature of the setting which limited their effectiveness. A theoretical framework in which to locate the results of the study is explored using cybernetic learning theory and the notion of hyperreality, using the works of Jean Baudrillard. A method for innovation and changing practice in the special hospital setting is suggested. PMID- 1430641 TI - Of sex and status: a study of the effects of gender and occupation on nurses' evaluations of nursing research. AB - Despite wide recognition that nursing must increase its research base, there still appears not only to be a shortfall in published nursing research but also a marked failure to implement research findings into clinical practice. One possible explanation for these problems is that nursing research may not be valued by peer professionals. To investigate this possibility, a study was designed to test the hypothesis that nurses would underrate the quality of papers they believed to have been produced by a nurse as opposed to a doctor, even when the status of the authors was randomly assigned to the papers. Thirty-one nurses were asked to rate two comparable papers on a number of criteria. Half the sample was told that the first paper had been written by a nurse and the second by a doctor; for the remainder of the sample, the order of authorship was reversed. A series of related t-tests was performed on the sample's evaluations in order to ascertain whether the status of the author affected perceptions of quality. No difference was found in the sample's judgement of overall quality, clarity of expression, expertise on the topic in question or contribution to current knowledge. However, significant differences were found in attributed grasp of research design and statistical analysis, with the nurse being judged as inferior on both (t = 1.71, d.f. = 30, P < 0.05; t = 1.72, d.f. = 30, P < 0.05 respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430643 TI - Method slurring: the grounded theory/phenomenology example. AB - Increasingly, qualitative research methods are being embraced by nurse researchers because these approaches allow exploration of human experience. Failure to explicate qualitative methodologies is resulting in a body of nursing research that is either mislabelled or is classified broadly as qualitative and subject to charges that qualitative research lacks rigour. In this paper, the authors discuss the importance of specificity in methodology and distinguish between phenomenology and grounded theory, two frequently misused terms in the description of qualitative methodology. PMID- 1430644 TI - Nursing science in The Netherlands: the Utrecht contribution. AB - The two goals of a 5-year nursing science project at the State University of Utrecht were the establishment of graduate nursing science studies and a nursing research programme. The project formally started on 1 January 1987 and is now nearing completion. This paper builds on a paper previously published in the Journal of Advanced Nursing. It first describes the history of nursing science in The Netherlands and sets out to demonstrate how the Utrecht goals were achieved. PMID- 1430645 TI - Staff turnover among hospital nurses. AB - Nursing staff turnover remains a financial concern to public as well as private institutions, and it has an impact on staff morale and working practices. Evidence suggests that staff turnover could also have a detrimental effect on patient care. Numerous studies have examined the reasons why staff leave their jobs, but these have often produced conflicting findings and have frequently relied upon bivariate correlation or multiple regression techniques. The availability of analytical techniques such as structural modelling provides an opportunity to examine several aspects of turnover behaviour simultaneously, and overcome some of the methodological difficulties encountered by prior research. This study involved 221 female nurses working full-time in hospitals to examine aspects of the nursing turnover model. Using modelling techniques, this current study found job satisfaction and participation at work to be important variables in the turnover process. This is in keeping with other models of nursing turnover. PMID- 1430646 TI - The emerging role of the nurse teacher in Project 2000 programmes in England: a literature review. AB - This paper explores the literature on the role of the nurse teacher in the United Kingdom, in order to support a research study on the role of the nurse teacher as it emerges in Project 2000 programmes in England. Explicit within the reform of nurse education is a change in the role of the teacher. It is being influenced, first, by the creation of colleges of nursing and midwifery and their links to higher education, secondly, by the content and academic level of the course and, thirdly, by the supernumerary status of the student. Studies carried out on the activities nurse teachers undertake highlight the complex and multifaceted nature of the role. Excessive paper work, meetings and lack of autonomy are given as dissatisfying aspects of their work leaving only a small proportion of their time for classroom and clinical teaching. The literature suggests that the nurse teacher is required in Project 2000 to be a nurse, a teacher, a graduate in a specialist subject and clinically and academically credible. The study, which is mentioned briefly in this paper, will critically analyse the key components of the role of the nurse teacher as it emerges in the Project 2000 courses in England. The methodology and findings will be discussed in a later paper. PMID- 1430647 TI - Literary referees. PMID- 1430648 TI - From policy to privacy--a perilous passage. PMID- 1430649 TI - Patient outcomes research--nursing, an important component. PMID- 1430650 TI - Critical care--the cost of quality. PMID- 1430651 TI - A microcosm for learning. PMID- 1430652 TI - Are preceptors for orientation of new nurses effective? AB - The intent of this secondary analysis of a large data set was to provide empirical data on the benefits of preceptorship programs for orientation. Do nurses with preceptors have more satisfaction, social integration, and professionalism; less turnover; and better performance? The subjects were newly employed nurses, 177 were assigned to preceptors, and 98 did not have preceptors. The subjects completed questionnaires at three time periods: during the first few weeks on the job and at 6 and 12 months after employment. Data were analyzed by student's t test and chi square analysis. On average, nurses with preceptors and less education and experience and were more involved with family. They worked on units with sicker patients. Nurses with preceptors were more satisfied with social and psychological rewards initially and had more of a feeling of self regulation. Previously employed nurses with preceptors reported more social integration at 6 and 12 months. The study provides beginning evidence that preceptors are beneficial for nurses who have limited education and experience. PMID- 1430653 TI - On the way to scholarship: from master's to doctorate. AB - Progress in the discipline of nursing is predicated on the development of a community of scholars who have passion for substance. Nurse educators are challenged to develop programs and environments that stimulate and nurture scholarship. However, doctoral education that enhances scholarship encompasses more than coursework. Strategies for the development of scholarly doctoral education are discussed in this article. PMID- 1430655 TI - A statewide study of academic variables affecting performance of baccalaureate nursing graduates on licensure examination. AB - The purpose of this study was to validate, using a statewide sample, findings from two previous smaller studies investigating the relationships between admission selection variables and subsequent achievement in baccalaureate nursing programs and performance on the National Council Licensure Examination for Registered Nurses (NCLEX-RN). Subjects for this study were 1,069 graduates of nine Iowa basic baccalaureate nursing programs. The analyses included three major components. The first addressed the relationship between admission selection variables and subsequent achievement in the nursing programs and performance on a standardized nursing achievement test (AssessTest) and the NCLEX-RN. The second component investigated the extent to which achievement in nursing courses predicted performance on the NCLEX-RN. In the third component a path analysis was used to formulate a causal model describing the relationships among the variables in the study. The results of the study suggest that students' prenursing grade point average and American College Testing scores predict their performance on the NCLEX-RN. Knowledge of performance predictors can both facilitate admission selection and the use of educational resources to develop nursing competence and promote success in obtaining licensure to practice. PMID- 1430654 TI - Differentiated practice: the evolution of professional nursing. AB - Differentiated practice identifies and uses three distinct nursing roles to create a comprehensive nursing care delivery system that meets client needs across the health care continuum. Clearly defined associate degree in nursing, bachelor's of science in nursing, and master's science in nursing competencies present career opportunities for professional nurses at the bedside providing, integrating, or managing client care as well as options in management, education, and regulation. An evolutionary paradigm shift required of all nurses is the awareness that each nurse is not the whole of nursing, but rather each nurse contributes to the whole of nursing. A nursing community comprised of differentiated roles that are mutually valued and well integrated will position nursing as a powerful force in meeting the diversity and complexity of health care needs in contemporary society. PMID- 1430656 TI - Success-failure on the National Council Licensure Examination for Registered Nurses by nurse candidates from an accelerated baccalaureate nursing program. AB - Nine years of data from first-time nurse candidates taking the National Council Licensure Examination for Registered Nurses (NCLEX-RN) were examined to identify predictors of successful performance and determine probabilities of success. Using logistic regression, four statistical models at strategic time periods during an accelerated baccalaureate nursing program were tested to see when intervention might be initiated to influence student performance on the NCLEX-RN. By the end of the first semester the model could predict failure for 94 per cent of those who failed, but it was less consequential in correctly predicting success of those who passed. Significant variables placing nurse candidates at risk included their first-semester grade point average, sex, and whether they were foreign educated. By the end of the second semester, with each full letter grade increase in cumulative grade point average, nurse candidates had a 46 times better chance of passing the NCLEX-RN; American-educated nurse candidates had a 4.5 times better chance of passing than their foreign-educated counterparts. At the end of the final semester, with each full letter grade increase on the final cumulative grade point average, nurse candidates had a 97 times greater likelihood of performing successfully on the NCLEX-RN. PMID- 1430657 TI - Natural law as a unifying ethic. AB - Natural law asserts that there is an objective moral order that human intelligence can understand and that societies are bound in conscience to follow. In 1772, George Mason appealed to natural law in denouncing a slavery statute in Virginia. This same ethic was called on to convict Nazi war criminals of crimes against humanity in 1948. In the last decade, natural law has enjoyed a resurgence in the medical biomedical ethics literature. It has appeared less frequently in the nursing literature and has been summarily dismissed when it has appeared. Only one nurse ethicist used natural law in discussing ethical issues (organ transplantation). Although further development of this philosophy is required, this ethic shows great promise as a guide to decision making in nursing. PMID- 1430658 TI - The social networks of bipolar affective disorder patients. AB - The social interaction parameters of a carefully delineated group of bipolar patients were compared to those of a random New Zealand community sample. The bipolar subjects had significantly lower scores for perceived availability and adequacy of both intimate and diffuse social relationships. Their mean scores did not differ from those of the subgroup in the random community survey who were classified as showing psychiatric morbidity, most of whom were depressed. Social interaction scores were negatively correlated with the bipolar patients' age and duration of illness. Those bipolar subjects with a predominance of manic episodes had lower mean values for their social interaction indices than those with more depressions. The results may suggest that the longer the illness continues, the greater is the impoverishment of the sufferer's social interaction patterns. Overall, manic episodes appeared to have a more deleterious effect on social relationships than depressive episodes. PMID- 1430659 TI - High-dose fluoxetine in the treatment of depressed patients not responsive to a standard dose of fluoxetine. AB - In a four-week, open label study of major depression, 15 patients who had failed to respond to a trial of fluoxetine 20 mg/day of 8-12 weeks duration were then treated with fluoxetine 40 mg/day for one week and then, if tolerated, with either 60 or 80 mg/day. The mean HAM-D-17 and CGIS scores of these 15 patients decreased significantly at the end of 4 weeks on a higher dosage of fluoxetine (60 or 80 mg/day) with respect to the beginning of the four-week study. No significant side-effects were noted. PMID- 1430660 TI - Folates and post partum depression. AB - Hypofolatemia can cause psychiatric disturbances of a depressive nature. Pregnancy and delivery are often associated with hypofolatemia. This study was conducted to determine if hypofolatemia at day 3 post partum is a risk factor for baby blues or post partum depression. To study this hypothesis, 131 post partum women were followed prospectively for the 3 months immediately following delivery. 19% were found to have 'baby blues', as defined by a score greater than 20 on Pitt's scale (Pitt, 1968, J. Psychiatry 114, 1325-1335) and 12% had post partum depression as defined by a score greater than 7 on QD2A scale (Pichot et al., 1984, Rev. Psycholog. App. 34, 229-250, 323-340), within the three months post partum. No relationship was observed between the serum or erythrocyte folate levels on the third day following delivery and the maternal post partum depression scores. A statistically significant correlation between post partum depression and previous psychiatric disturbance was, however, observed. PMID- 1430661 TI - A psychosocial profile of women with premenstrual dysphoria. AB - Sixty women from the community were used in this study to identify a profile of women who experience premenstrual dysphoria. Women with prospectively confirmed premenstrual dysphoria (PMD +; N = 24) were compared to women with prospectively unconfirmed premenstrual dysphoria (PMD -; N = 15) and controls (PMD control; N = 21). Over one menstrual cycle daily records of physical, emotional and behavioural symptoms were completed on the Daily Ratings Form. Other self report measures obtained were the Premenstrual Assessment Form, Rotter's Internal External Locus of Control, the Locke-Wallace Marital Adjustment Scale, and the State-Trait Anxiety Inventory. A psychiatric history was obtained during an interview. Analyses showed that premenstrually, PMD + and PMD - groups could be significantly differentiated from controls on reports of premenstrual dysphoric changes and levels of state and trait anxiety. Postmenstrually, they could be significantly differentiated from controls firstly, by history of affective disorder and locus of control and secondly, by premenstrual dysphoric changes. There were no significant differences between the PMD+ and PMD- women on most of the self report measures either at pre or post menstrual assessments. The present findings suggest that the characteristic profile of PMD+ and PMD- women is one of being symptomatic premenstrually in relation to dysphoric changes and levels of state and trait anxiety. Postmenstrually these symptoms appear to be superimposed on a background of a history of affective disorder and an external locus of control orientation. PMID- 1430662 TI - Suicides and parasuicides in a high-risk patient group on and off lithium long term medication. AB - 68 patients with affective disorders, and receiving lithium prophylaxis in a specialized lithium clinic were followed up for 8 years on average. Patients were selected for this study according to 2 criteria: They had been given lithium for at least 12 months, and they had attempted suicide at least once before onset of lithium prophylaxis. Outcome was analysed in terms of suicidal and parasuicidal behaviour. 55 patients took their lithium regularly, 13 discontinued or dropped the medication. One third of those patients having discontinued the medication died from suicide. Only one suicide occurred in patients with regular lithium intake and proven compliance during the last check before death. An impressive drop of parasuicides was observed in responders as well as in apparent non responders. In total, 11 of 13 patients showed suicidal or parasuicidal behaviour 2 weeks-44 months after lithium discontinuation, which in about half of these cases took place on advice or with consent of the treating psychiatrist. It is concluded that lithium may have specific anti-suicidal properties, possibly related to its anti-aggressive effect, and that patients apparently not responding satisfactorily in terms of reduced number of episodes may still be protected against suicide or parasuicide. PMID- 1430663 TI - Is the tyramine test for depressive illness useful in elderly patients? AB - There were no significant differences in tyramine sulphate excretion following tyramine ingestion between elderly depressed, demented or control patient groups, in contrast with younger subjects where this test is a trait marker for unipolar endogenous depression. There are inherent problems in urine collection studies in the elderly and the results may have been influenced by the medication that elderly patients have to take for other disorders. This study suggests that the tyramine test is unlikely to be of clinical usefulness in the over 65 age group. PMID- 1430664 TI - Clinical correlates of response to DST. The Dexamethasone Suppression test in depression: a World Health Organisation collaborative study. AB - From 9 centres 293 patients took part in the WHO-collaborative study on Dexamethasone-Suppression-Test (DST) in depression to examine the relationship of psychopathological and psychiatric history information to cortisol-levels and suppression/non-suppression status. Differences between the centres were large and significant on nearly all of the measures. The predictor analyses generally suffered from numerically weak correlations with many variables correlating to sex and age. Therefore analyses of the data were adjusted for centre-, sex-, and age-influences. The best predicting features of cortisol were 'fitful, restless sleep', 'change of bodyweight' and 'affective disorders in blood relatives'. The last 2 items together with 'hypersomnia' and 'ideas of insufficiency' were the best predictors of suppression/nonsuppression status. However, statistical evidence did not seem to be strong enough to describe a typical symptom profile of a depressive cortisol suppressor or nonsuppressor. PMID- 1430665 TI - Puerperal psychoses: a clinical case study with follow-up. AB - Thirty cases of post-partum psychotic disorders occurred between 1973 and 1987 and hospitalized at the Psychiatric Ward of Florence University were studied and followed up. A structured diagnostic interview was used, which explored DSM Ill-R diagnosis both for mood disorders and for psychotic features. The psychotic symptoms had started within 8 weeks of parturition in all cases. Only 36.7% of the patients showed no subsequent pathology after the puerperal symptoms. The diagnoses, both at the index episode and at the follow-up, revealed a great predominance of mood disorders and the absence of schizophrenia. The follow-up survey showed a greater proportion of bipolar disorders than it appeared at the puerperal onset of the disease. A high frequency of puerperal psychotic relapses has also occurred after subsequent deliveries during the follow-up period. PMID- 1430667 TI - Risk for affective disorder and alcohol and other drug abuse in the relatives of affectively ill adoptees. AB - We investigated the risk for substance abuse in the biological relatives of adoptees with affective illness, controlling for potential confounds, and additionally assessed risk by probands' and relatives' gender. Our sample consisted of 67 index adoptees with affective illness, matched control adoptees, and their biological and adoptive relatives. Both affective illness and substance abuse were more common in the biological relatives of affectively ill adoptees than in controls' relatives. Affective illness was more common than substance abuse among female index biological relatives, with the opposite pattern observed among male relatives. PMID- 1430666 TI - Single photon emission tomography with 99mTc-exametazime in major depression and the pattern of brain activity underlying the psychotic/neurotic continuum. AB - Forty patients with a major depressive episode were investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, an intravenous ligand taken into brain in proportion to regional cerebral blood flow, thereby providing an estimate of regional metabolism. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. They also completed a range of neuropsychological tests. They were compared with 20 control subjects matched for age, gender, premorbid intelligence and education. The uptake of 99mTc-exametazime was expressed for a range of anatomically defined regions of interest relative to calcarine/occipital cortex. The depressed group showed reduced uptake in the majority of cortical and sub cortical regions examined, most significantly in temporal, inferior frontal and parietal areas. Unexpectedly, there was a strong positive association between uptake and scores on the Newcastle scale, especially in cingulate areas and frontal cortex. After removing the variance attributable to the Newcastle ratings, however, there emerged the expected negative association between Hamilton scores and anterior tracer uptake. The associations between neuropsychological impairment and regional brain uptake of tracer in part reflected the pattern seen with the Newcastle scale: for example, impairment of memory function correlated with higher uptake into posterior cingulate areas. We propose that depressive illness may be characterised by two processes. One leads to an overall reduction in anterior neocortical function, perhaps related to symptom severity. The other mechanism is manifest as relatively increased function, most notably within cingulate and frontal areas of the cerebral cortex in association with psychotic symptoms. The findings offer new understanding of the brain states underlying depressive illness and a potential focus to subsequent neuropharmacological analysis. PMID- 1430668 TI - Depression and learning disabilities in children. AB - Occurrence of learning disabilities was determined in 30 inpatient children aged 6-12 with major depressive disorder (MDD). Learning disabilities (LD) occurred seven times more often compared to community base rates (33% v 4.7%). While rates of comorbid diagnoses, severity of depression, and children's and parents' reports (DICA-C, DICA-P) did not differ between groups, teachers' reports (TRS, TRF) indicated increased classroom problems and poorer adaptive functioning in MDD/LD subjects (P < 0.0001). PMID- 1430669 TI - Diagnostic specificity of the dependent and self-critical personality dimensions in major depression. AB - Validational studies of self-critical and dependent personality dimensions as vulnerability factors for depression have been tested primarily with depressed samples, employing research designs devised to address state vs. trait and trait situational congruity issues. In this study we examined the diagnostic specificity to depression of these two personality dimensions, comparing Self Criticism and Dependency scores as measured by the Depressive Experiences Questionnaire (DEQ) in two samples of outpatients: (1) panic disorder with agoraphobia; and (2) non-psychotic, unipolar major depression. As hypothesized, the two groups differed on Self-Criticism, with the depressed group scoring higher, but no differences were found for Dependency. These findings were similar even when depressed mood was partialed out. These results complement a growing body of research associating Self-Criticism, as specifically measured by the DEQ, with depression. PMID- 1430670 TI - Imipramine and weight gain during the long-term treatment of recurrent depression. AB - The recently completed long-term maintenance trial of full-dose imipramine for recurrent unipolar disorder provided an opportunity to examine the extent to which such doses (200-300 mg daily) are associated with persistent and adverse side effects, particularly weight change. In 115 patients we monitored weight change during the three-year maintenance treatment phase to the point of trial completion, recurrence or termination. No differences were noted between individuals receiving active medication (average gain of 5.8 lbs. during an average treatment period of 725 days) versus those randomized to the 'no-drug' cells (average gain of 2.8 lbs. during an average treatment period of 422 days). Numerous other factors such as body mass index, previous weight gain and gender did not play a differential role in establishing why some individuals gained weight during long-term treatment of depression regardless of specific treatment. PMID- 1430671 TI - Diagnostic accuracy in adolescents of several depression rating scales extracted from a general purpose behavior checklist. AB - Receiver Operating Characteristics (ROC) analysis of six depression scales extracted from the Child Behavior Checklist (CBCL) and Youth Self-report (YSR) in a clinically referred sample of adolescents (N = 667) showed that their performance in discriminating between depressed and not depressed patients was comparable to other specifically designed depression rating scales (area under the ROC curves between 0.75 and 0.82). Performance was better for boys than for girls. These results suggest that specific depression self-report rating scales may be unnecessary in adolescents if CBCL or YSR data are available, and that self-reports are not more accurate than parent-reports in the identification of depression in this age group. PMID- 1430672 TI - The effect of cholesterol screening on college students. AB - This study was designed to determine the effect of cholesterol screening on college students' knowledge retention and self-reported behavior change. Students (N = 180, age M = 21.4 +/- 4.1 years) enrolled in a self-paced personal fitness course participated in a screening accompanied by two educational handouts and oral information from the technician. Six weeks later, subjects completed a questionnaire that revealed that 76% remembered their exact cholesterol level. Only 36%, however, remembered specifically why their cholesterol level was important, 22% remembered the three National Cholesterol Education Program (NCEP) categories and values, and only 36% could fully identify their correct NCEP follow-up. Chi-square analyses revealed no significant differences between expected and observed frequencies for gender or cholesterol category by cognitive information retention. Analyses did reveal more self-reported dietary and exercise changes for those testing above 200 mg/dL than for those below 200. Although college students may remember their cholesterol level after 6 weeks and may take some action if they are above the desirable level, the knowledge base established in a typical screening situation appears inadequate. Educational efforts accompanying most screenings should be improved, and some attention should be given to young adults who test at the high end of the desirable category. PMID- 1430673 TI - Medical students' exposure to formaldehyde in a gross anatomy dissection laboratory. AB - The authors studied 150 first-year medical students exposed to formaldehyde during the dissection of cadavers in a gross anatomy laboratory. As a reference group, they used 189 third- and fourth-year medical students matched for sex, ethnic group, and age. Environmental and personal samples were collected to determine the exposure to formaldehyde among the first-year students. The mean concentration of formaldehyde in parts per million (ppm) in the area was 0.50 ppm (range = 0.40-0.60 ppm) and the personal sample was 0.74 ppm (range = 0.41-1.20 ppm). No significant differences were noted in the pre- and post-exposure mean FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) among the 22 randomly selected exposed male and female subjects. Significant differences, however, were observed in the exposed group for symptoms of decreased ability to smell, eye irritation, throat irritation, and dry mouth in comparison with the reference group. These symptoms were also significantly related to the time and place of occurrence. Medical schools should take more concrete measures to reduce students' exposure to formaldehyde. Meanwhile, although it is not now the practice in most medical schools, students should have ready access to goggles and respirators when working in dissection laboratories. PMID- 1430674 TI - The history of sections in the American College Health Association. AB - The founders of the American College Health Association (ACHA) recognized the importance of regional groups (affiliates) and worked actively to foster their formation and continued existence. In 1932, D. F. Smiley, MD, described the concept of establishing ACHA regions and suggested combining institutional membership in both the national and regional organizations. Significant affiliate representation in the association's governance structure finally became a reality in 1987, when regional representatives became permanent members of the board of directors. Standing committees of the association were transformed into the present ACHA sections in 1957, and a new category for individual membership established for college health professionals interested in participating in educational activities of the new sections. In many ways, the changes in the association's governance that occurred in 1987 are reminiscent of the original structure of the 1920-1970 era, when the organization was much smaller and essentially an association of college health center directors. PMID- 1430675 TI - The impact of influenza vaccination on respiratory illness at a boarding school. AB - We studied the impact of influenza vaccine during an outbreak of influenza at a 989-student boarding school in January to March, 1989. By February 6, 120 (17%) of 690 students completing survey questionnaires had been ill with fever and respiratory symptoms. Eighty-seven students had received influenza vaccine in the previous 18 months; these students had an attack rate half that of the unvaccinated students (9% v 19%; vaccine efficacy = 50%, confidence interval = 0% 70%). We estimate that, if the entire student body had been vaccinated, influenza like illness could have been prevented in 162 students (16% of the school), and that preventing this illness could have avoided at least 482 student-days of missed classes, or approximately one student-day for each 1.8 additional doses of vaccine given. This study suggests that, when feasible, a broad influenza immunization policy for healthy students at residential schools should substantially decrease the disruption of school activities caused by influenza. PMID- 1430676 TI - Who should get influenza vaccine? PMID- 1430677 TI - Connotative meanings assigned to contraceptive options. AB - Healthy People 2000: National Health Promotion and Disease Prevention Objectives states that the reduction of unintended pregnancies is one of the primary health objectives for college-aged people. In addition, the reduction in rates of sexually transmitted diseases, with special emphasis on reducing the incidence of HIV infection, is an important objective for this population. One way of addressing these objectives is through promoting use of effective contraception methods. Attitudes toward a particular contraceptive option may play an important role in acceptance of, and predisposition toward, using a given method. The authors used semantic differential scaling to study the connotative meanings college students assigned to 13 contraceptive methods. They asked 751 students (mean age = 19.6 years) to rate each method of contraception, using 7-point scales composed of 15 bipolar adjective pairs. Scale internal consistency was estimated using Cronbach's alpha, and ranges were from .68 for douching to .92 for oral contraceptives. Respondents' rank-ordered approval ratings of the 13 options were as follows: oral contraceptives; abstinence; the condom; the diaphragm; the contraceptive sponge; female sterilization; rhythm; male sterilization; douching, the IUD, and vaginal suppositories (tied); spermicidal foam; and withdrawal. These results indicated general approval for methods that are effective in preventing conception. Semantic interpretation of selected contraceptive options differed by gender and race, but not by age. Implications for contraception education and future research issues are discussed. PMID- 1430678 TI - Gender-specific changes in students' sexual behaviors and attitudes at a southeastern university between 1973 and 1988. AB - This study investigated the gender-specific, self-reported sexual behaviors and attitudes of never-married college students attending a southeastern university in 1973 and 1988. Data were collected by means of a mailed questionnaire that remained essentially unchanged for both years. The authors found that both men and women reported an increase in heterosexual relationships that included sexual intercourse and a decrease in nonsexual relationships with the other gender. The majority of the students perceived themselves as adequately informed about sexuality and satisfied with their relationships, although the proportion of men who reported being satisfied with their relationships declined over the 15 years. The students indicated that sexuality education should focus primarily on information about AIDS and on preparation for marriage. PMID- 1430679 TI - Mechanism of benefit of combination thrombolytic therapy for acute myocardial infarction: a quantitative angiographic and hematologic study. AB - OBJECTIVES: The goal of this study was to lend insight into the mechanisms responsible for the beneficial effects of combination thrombolytic therapy. BACKGROUND: Combination thrombolytic therapy for acute myocardial infarction has been associated with less reocclusion and fewer in-hospital clinical events than has monotherapy. METHODS: Infarct-related quantitative coronary dimensions and hemostatic protein levels were evaluated in 287 patients with acute myocardial infarction during the early (90-min) and convalescent (7-day) phases after administration of recombinant tissue-type plasminogen activator (rt-PA), urokinase or combination rt-PA and urokinase. RESULTS: Minimal lumen diameter was similar in the 90-min and 7-day phases after treatment with rt-PA, urokinase and combination rt-PA and urokinase (0.72 +/- 0.45 mm, 0.62 +/- 0.53 mm and 0.75 +/- 0.58 mm, respectively, at 90 min, p = 0.16; and 1.05 +/- 0.56 mm, 1.12 +/- 0.72 mm and 0.94 +/- 0.54 mm, respectively, at 7 days, p = 0.22). In-hospital clinical event and reocclusion rates were less frequent in patients receiving combination therapy than in those receiving monotherapy (25% vs. 38% and 32% for rt-PA and urokinase, respectively, p = 0.084; and 3% vs. 13% and 9% for rt-PA and urokinase, respectively, p = 0.03), but these events were unrelated to early or late coronary dimensions. Patients receiving combination therapy or urokinase monotherapy had significantly higher peak fibrin degradation products (1,307 +/- 860 and 1,285 +/- 898 micrograms/ml vs. 435 +/- 717 micrograms/ml, respectively, p < 0.0001) and lower nadir fibrinogen levels (0.85 +/- 1.00 and 0.75 +/- 0.53 g/liter vs. 1.90 +/- 0.86 g/liter, respectively, p < 0.0001) than did those receiving rt-PA monotherapy. Peak fibrinogen degradation products indirectly correlated (p = 0.004) and baseline (p = 0.026) and nadir (p = 0.089) fibrinogen levels directly correlated with reocclusion. CONCLUSIONS: Lower in-hospital clinical event and reocclusion rates observed with combination thrombolytic therapy may relate to systemic hematologic factors rather than to the residual lumen obstruction after thrombolysis. PMID- 1430680 TI - Pathophysiology and prognostic significance of Holter-detected ST segment depression after myocardial infarction. The Tissue Plasminogen Activator: Toronto (TPAT) Study Group. AB - OBJECTIVES: We performed Holter monitoring on days 4 and 7 after acute myocardial infarction in 109 patients to assess whether ST segment shift would identify those with more severe coronary artery disease, left ventricular dysfunction and unfavorable prognosis. BACKGROUND: Silent myocardial ischemia is a frequent and prognostically significant event after acute myocardial infarction. However, the specific pathophysiologic mechanisms and the impact of thrombolytic therapy are uncertain. METHODS: In addition to Holter monitoring, patients underwent exercise testing, radionuclide angiography on days 1 and 9 and quantitative coronary angiography on day 9. RESULTS: Thirty-five patients (32%) had ST segment depression and had similar recombinant tissue-type plasminogen activator (rt-PA) treatment assignment and a reduced cross-sectional area of the infarct-related artery (0.59 +/- 0.57 vs. 1.04 +/- 1.26 mm2, p < 0.05). Global left ventricular function improved from day 1 to day 9 in patients without (4% +/- 11%, p < 0.001) but not in those with (0% +/- 7%) ST segment depression. In-hospital event rates were similar; however, follow-up 18 +/- 11 months after hospital discharge revealed a greater frequency of death and recurrent myocardial infarction in patients with compared with those without ST segment depression (27% vs. 6%, p = 0.03). CONCLUSIONS: After acute myocardial infarction, approximately one third of patients have ST segment depression on Holter monitoring, independent of the use of thrombolytic therapy. The unfavorable prognosis observed in these patients may be related to greater lumen obstruction in the infarct-related artery and lack of improvement in left ventricular function. PMID- 1430681 TI - Ischemic cardiomyopathy: endomyocardial biopsy and ventriculographic evaluation of patients with congestive heart failure, dilated cardiomyopathy and coronary artery disease. AB - OBJECTIVES: This study was designed to define clinical and pathophysiologic similarities and differences between patients with ischemic and idiopathic dilated cardiomyopathy. BACKGROUND: Significant coronary artery disease in patients with new onset congestive heart failure due to dilated cardiomyopathy has important prognostic and therapeutic implications. METHODS: Clinical, histologic, ventriculographic and hemodynamic features of patients with dilated cardiomyopathy who underwent coronary angiography were reviewed. RESULTS: Patients with ischemic cardiomyopathy (n = 21) compared with those with idiopathic cardiomyopathy (n = 40) had similar presenting symptoms, durations of illness, and coronary risk factor profiles, with the exception of a greater prevalence of cigarette smoking (71% vs. 39%, p = 0.028) and male gender (100% vs. 70%, p = 0.014). Endomyocardial biopsy specimens from patients with ischemic cardiomyopathy demonstrated a greater prevalence of replacement fibrosis (48% vs. 8%, p = 0.001) and a lesser degree of histologically assessed myocyte hypertrophy (mean grade 0.5 +/- 0.7 vs. 1.3 +/- 1.3, p = 0.015). Although ventriculographically determined regional dyskinesia was present in both groups, there was a higher prevalence of two or more adjacent segments in the ischemic cardiomyopathy group (50% vs. 10%, p = 0.03). This ischemic group had hemodynamic variables associated with a worse prognosis: higher pulmonary artery wedge pressure (23 +/- 10 vs. 15 +/- 9 mm Hg, p = 0.006) and lower cardiac index (2.0 +/- 0.5 vs. 2.3 +/- 0.5 liters/min per m2, p = 0.044). Also, in this group, patients had a mean of 2.6 +/- 0.7 diseased vessels; 15 (71%) of 21 patients had triple-vessel disease and 18 (86%) of 21 had at least one occluded or suboccluded artery. CONCLUSIONS: 1) Patients with ischemic and idiopathic cardiomyopathy may be clinically indistinguishable unless coronary angiography is performed. 2) A greater prevalence of replacement fibrosis and a lesser degree of myocardial hypertrophy in patients with ischemic cardiomyopathy may account for the greater extent of hemodynamic decompensation observed at presentation. PMID- 1430682 TI - Relation between ventilation and carbon dioxide production in patients with chronic heart failure. AB - OBJECTIVES: The aim of this study was to analyze the relation between ventilation and carbon dioxide production and the control of ventilation in patients with chronic heart failure. BACKGROUND: Patients with chronic heart failure exhibit an increased ventilatory response to exercise. Ventilation is closely linked to carbon dioxide production, producing a high correlation between the two variables. This relation is nonlinear at high levels of exercise. METHODS: The ventilation/carbon dioxide production ratio during exercise was examined in 29 patients with chronic heart failure and 9 normal volunteers. RESULTS: In the patients with heart failure, there were three patterns: in the least severely affected patients, the pattern was similar to that of the normal subjects, with an initial decrease in the ventilation/carbon dioxide production ratio to a plateau maintained during exercise; in more severely affected patients, there was an increase in the ratio at the end of exercise, and in the most severely affected patients, the ratio increased from the outset of exercise. The ventilation/carbon dioxide relation is not adequately described by a straight line relation. CONCLUSIONS: The ventilation/carbon dioxide ratio is not fixed, and the changes that occur in this ratio reflect either a noncarbon dioxide driven ventilatory stimulus or an increase in ventilation-perfusion mismatch due to increased dead space ventilation. The different patterns of this ratio may provide clues to the pathophysiologic mechanisms of the excessive ventilation and breathlessness seen during exercise in chronic heart failure. PMID- 1430683 TI - Effects of time and previous acute rejection episodes on coronary vascular reserve in human heart transplant recipients. AB - OBJECTIVES: This study examined whether previous rejection episodes may have deleterious effects on coronary vascular reserve of heart transplant recipients months after transplantation. BACKGROUND: Coronary reserve has been demonstrated to be within the normal range in long-term transplant patients without previous episodes of rejection. Conversely, acute rejection is associated with a dramatic reduction of coronary reserve, which is rapidly restored after therapy. METHODS: Coronary flow velocity was measured by intracoronary Doppler catheter before and after a maximally vasodilating dose of intracoronary papaverine in 16 control subjects and in 59 transplant patients classified into three groups with respect to time after transplantation: 1 to 6 months (group 1, n = 17), 7 to 18 months (group 2, n = 22) and > 18 months (group 3, n = 20). Coronary vascular reserve was evaluated through peak/rest coronary flow velocity ratio and minimal coronary vascular resistance index. All patients had normal findings on left ventricular angiography and coronary arteriography and a normal left ventricular mass. RESULTS: Arterial pressure was normal in all groups. Heart rate in the three groups of transplant patients, mean aortic pressure in groups 1 and 2, left ventricular systolic pressure in group 2 and rate-pressure product in groups 1 and 2 were higher than in control subjects. Average number of rejection episodes per patient was similar in the three groups of patients (group 1, 2.4 +/- 1.4; group 2, 2.5 +/- 1.9, and group 3, 2.1 +/- 1.3). Results showed no difference between each group of transplant patients and control subjects for peak/rest coronary flow velocity ratio (control subjects, 5.2 +/- 0.8; group 1, 5.3 +/- 1.5; group 2, 4.9 +/- 1.2, and group 3, 4.4 +/- 1.6) and for minimal coronary vascular resistance index (control subjects, 0.18 +/- 0.03; group 1, 0.18 +/- 0.04; group 2, 0.20 +/- 0.06, group 3, 0.23 +/- 0.11). In addition, patients with zero or one rejection episode had similar values of peak/rest coronary flow velocity ratio and minimal coronary vascular resistance index (4.3 +/- 1.3 and 0.23 +/- 0.10, respectively, n = 22) as did those with one or two rejection episodes (5.1 +/- 1.5 and 0.19 +/- 0.07, respectively, n = 24), and those with four or more episodes (5.2 +/- 1.4 and 0.19 +/- 0.05, respectively, n = 13). CONCLUSIONS: This study showed that coronary vascular reserve remains within normal range and is independent from the number of previous episodes of rejection until late after transplantation in human heart transplant patients with angiographically normal coronary arteries. PMID- 1430684 TI - Excessive vasoconstriction in rheumatic mitral stenosis with modestly reduced ejection fraction. AB - OBJECTIVES: The primary hypothesis examined was that underfilling due to inflow obstruction accounts for modestly depressed ejection performance in mitral stenosis. Having found little evidence to support this hypothesis, we sought to determine other factors that might differentiate patients with different levels of ejection performance. METHODS: Ventricular load and performance were compared in two groups of patients before and immediately after successful balloon valvuloplasty that was not complicated by mitral regurgitation: those in whom prevalvuloplasty ejection fraction was > or = 0.55 (group I, n = 10) and those in whom it was < 0.55 (group II, n = 11). RESULTS: Before valvuloplasty, mitral valve area was less in group II (0.65 cm2) than in group I (0.84 cm2, p = 0.02), but end-diastolic pressure (12 vs. 12 mm Hg in group I), end-diastolic wall stress (46 vs. 44 kdynes/cm2 in group I) and end-diastolic volume (152 vs. 150 ml in group I) were not less in group II, nor were these variables significantly reduced compared with those of a normal control group. In group II, end-systolic volume was larger (77 vs. 55 ml in group I, p = 0.001) and cardiac output was less (3.1 vs. 3.6 liters/min in group I, p = 0.03), possibly owing to higher systemic vascular resistance (2,438 vs. 1,921 dynes.s.cm-5 in group I, p = 0.05) and end-systolic wall stress (273 vs. 226 kdynes/cm2 in group I, p = 0.06), although mean arterial pressure in the two groups was similar (91 vs. 84 mm Hg in group I, p = 0.22). Group II patients also had higher values for pulmonary vascular resistance (712 vs. 269 dynes.s.cm-5 in group I, p = 0.03) and mean pulmonary artery pressure (47 vs. 29 mm Hg in group I, p = 0.02) despite similar values for mean left atrial pressure (20 vs. 18 mm Hg in group I, p = 0.35). After valvuloplasty, mitral valve area increased by 2.5- and 3-fold, respectively, in group I (to 2.1 cm2) and group II (to 2.0 cm2). Modest increases in left ventricular end-diastolic pressure, end-diastolic stress and end diastolic volume (+9%) after valvuloplasty were statistically significant only for group II. End-systolic wall stress did not decline in either group II (281 kdynes/cm2) or group I (230 kdynes/cm2), and ejection fraction failed to increase significantly (0.49 to 0.51 for group II and 0.62 to 0.61 for group I) after valvuloplasty. Contractile performance estimated with a preload-corrected ejection fraction-afterload relation was within or near normal limits in all 19 patients in whom it was assessed. CONCLUSIONS: Excessive vasoconstriction may account for the higher afterload, lower ejection performance and lower cardiac output observed in a subset of patients with mitral stenosis because contractile dysfunction could not be detected and left ventricular filling--which was not subnormal despite severe inflow obstruction--improved only modestly after valvuloplasty. PMID- 1430685 TI - Effects of mitral regurgitation on pulmonary venous flow and left atrial pressure: an intraoperative transesophageal echocardiographic study. AB - OBJECTIVES AND BACKGROUND: Pulmonary venous flows recorded by pulsed wave Doppler transesophageal echocardiography examination can be used to assess the severity of mitral regurgitation. Pulmonary venous flows are also related to left atrial pressures; however, the determinants of these flows have yet to be characterized in the presence of mitral regurgitation. METHODS: We simultaneously recorded intraoperative pulmonary venous flows by transesophageal echocardiography and left atrial pressures by direct left atrial puncture in 16 patients with different grades of mitral regurgitation: 2+ (n = 5), 3+ (n = 4) and 4+ (n = 7). Pulmonary venous peak systolic and diastolic flow velocities and peak reversed systolic flow velocities were compared with left atrial pressure a and v waves, a x and v-y descent values and left atrial volumes. RESULTS: Pulmonary venous systolic to diastolic flow ratios correlated with decreases in left atrial pressure a/v ratios and with increases in the v waves of patients with higher grades of mitral regurgitation. Univariate analysis revealed that the best determinants of the pulmonary venous systolic to diastolic flow ratio were the left atrial pressure v wave (r = -0.76), the v-y descent value (r = -0.73) and the a/v ratio (r = 0.71). Lower correlations were found for left atrial end systolic (r = -0.48) and end-diastolic (r = -0.42) volumes. Reversed systolic flow was present in patients with 4+ mitral regurgitation, despite left atrial enlargement. CONCLUSIONS: Pulmonary venous flow can be used to assess the severity of mitral regurgitation and reflects the effects of mitral regurgitation severity on the left atrial pressure a and v waves. PMID- 1430686 TI - Evaluation of mitral leaflet motion by echocardiography and jet direction by Doppler color flow mapping to determine the mechanisms of mitral regurgitation. AB - OBJECTIVES: This study was designed to assess the accuracy of two-dimensional and Doppler echocardiography in determining the mechanism of mitral regurgitation, as compared with direct inspection of the valve at operation. BACKGROUND: Valve repair for mitral regurgitation offers substantial advantages over valve replacement, but it is technically more demanding and requires understanding of the mechanism of dysfunction. METHODS: We studied 286 patients undergoing mitral valve repair. Intraoperative two-dimensional echocardiography was used to classify mitral leaflet motion as excessive, normal or restricted. Doppler color flow mapping was used to evaluate the direction and origin of the mitral regurgitant jet. Two-dimensional and Doppler echocardiography were compared with intraoperative surgical determination of the mechanism of dysfunction, which also classified leaflet motion as excessive, normal or restricted. RESULTS: Two dimensional and Doppler echocardiography accurately diagnosed the mechanism of mitral regurgitation in 123 (93%) of 132 patients with posterior leaflet prolapse or flail, 30 (94%) of 32 patients with anterior leaflet prolapse or flail, 11 (44%) of 25 patients with bileaflet prolapse or flail, 6 (75%) of 8 patients with papillary muscle elongation or rupture, 31 (91%) of 34 patients with restricted leaflet motion or rheumatic thickening, 21 (72%) of 29 patients with ventricular annular dilation and 8 (62%) of 13 patients with a leaflet perforation or cleft. Of 13 patients with two mechanisms of dysfunction by surgical inspection, two dimensional and Doppler echocardiography correctly diagnosed one of the two mechanisms in 12 patients (92%), and both mechanisms in 5 patients (38%). Overall, echocardiographic determination of leaflet motion and Doppler determination of jet direction accurately diagnosed the mechanism of dysfunction in 242 (85%) of 286 patients. CONCLUSIONS: Echocardiography before mitral valvuloplasty provides a dynamic appraisal of the mechanism of dysfunction, enabling the surgeon to systematically understand the dysfunction and successfully apply the correct procedures to eliminate mitral regurgitation without valve replacement. PMID- 1430687 TI - Value and limitations of Doppler echocardiographic determination of mitral valve area in Lutembacher syndrome. AB - OBJECTIVES: Our objective was to compare the Doppler pressure half-time, Doppler continuity equation and two-dimensional echocardiographic planimetric methods of estimating mitral valve area in Lutembacher syndrome. BACKGROUND: Fluid dynamics theory predicts that mitral pressure half-time varies inversely with mitral valve area and directly with net chamber compliance and the peak early diastolic transmitral gradient in pure mitral stenosis. The effects of an atrial shunt on these interrelations have not been investigated. METHODS: Correlation and agreement between mitral valve area estimates obtained by the three methods and that obtained by cardiac catheterization was ascertained in 11 patients with Lutembacher syndrome. RESULTS: Valve areas determined by planimetry and the continuity equation method correlated and agreed well with catheterization measurements (r = 0.83 and 0.81, respectively). The pressure half-time method consistently overestimated mitral valve area; the extent of overestimation was greater in patients with larger atrial shunts. The hemodynamic pressure half-time was independent of the mitral valve area, chamber compliance and the peak transmitral gradient. It was dependent on the magnitude of the atrial shunt, although the correlation obtained was only fair (r = 0.61). CONCLUSIONS: These findings suggest that the Doppler pressure half-time method is an inaccurate measure of mitral valve area whenever an atrial shunt coexists with mitral stenosis. Planimetry and the Doppler continuity equation methods yield accurate estimates of mitral valve area in Lutembacher syndrome. PMID- 1430688 TI - Protection against ischemia during prolonged balloon inflation by distal coronary perfusion with use of an autoperfusion catheter or Fluosol. AB - OBJECTIVES: The purpose of this report was to study the protective effects of passive and active distal coronary perfusion during prolonged balloon inflation. BACKGROUND: Prolonged balloon inflation has been proposed to improve immediate and long-term results of percutaneous transluminal coronary angioplasty, but it requires protection against myocardial ischemia. METHODS: A 30-min balloon occlusion of the left anterior descending artery was performed in three groups of closed chest anesthetized dogs: 1) control (no distal coronary perfusion, n = 13), 2) passive distal coronary perfusion (autoperfusion catheter, n = 10), and 3) active distal coronary perfusion (infusion of the perfluorochemical Fluosol at 30 ml/min, n = 11). RESULTS: At 10 min of balloon inflation, echocardiographic wall motion indexes (scored from 1 [normal] to 5 [dyskinesia]) in the autoperfusion catheter and Fluosol groups (2.4 +/- 1.2 and 2.0 +/- 0.9, respectively) were significantly better than in the control group (3.6 +/- 0.4, p = 0.001), but at 25 min this improvement in wall motion had attenuated and became statistically insignificant when compared with values in the control group. Left ventricular end-diastolic pressure at peak inflation in the Fluosol group (19.5 +/- 5.5 mm Hg) was higher than in the control (7.6 +/- 3.6) and autoperfusion catheter (5.3 +/- 1.4, p < or = 0.01) groups. Pathologic evidence of infarction by tetrazolium staining was seen in three control dogs and in none of the other groups (p = 0.07). Ventricular tachycardia and fibrillation were less frequent in the autoperfusion catheter group (p = 0.02). Three deaths were observed in the control dogs, two in the Fluosol group and none in the dogs with an autoperfusion catheter (p = NS). CONCLUSIONS: Passive (the autoperfusion balloon catheter) and active (Fluosol) distal coronary perfusion methods are comparable and better than no perfusion in protecting the myocardium against ischemia produced by prolonged coronary balloon inflation in an experimental canine model. This protection is transient, attenuating after 10 to 25 min, and partial because there was no significant difference in the incidence of myocardial infarction and death among groups, although the latter observations may be related to small sample size. PMID- 1430689 TI - Intracoronary ultrasound predictors of adverse outcomes after coronary artery interventions. AB - OBJECTIVES: The purpose of this study was to determine the association between qualitative and quantitative lesion characteristics as assessed by intracoronary ultrasound imaging and adverse outcomes after coronary artery interventions. BACKGROUND: Restenosis and other adverse outcomes after coronary artery interventions may be difficult to predict from clinical or angiographic data. Intracoronary ultrasound imaging provides additional data that could prove useful. METHODS: Immediately after successful coronary artery interventions (angiographic residual stenosis < or = 50%), 69 patients underwent intracoronary ultrasound imaging. Images were assessed qualitatively for plaque composition and topography and for dissection. Quantitative data included measurement of minimal lumen diameter, lumen area, plaque area and percent area stenosis at the treatment and adjacent reference sites. Adverse outcome was defined as death, coronary bypass surgery, myocardial infarction or angiographic restenosis. RESULTS: Of the 69 patients, 1 died, 3 had bypass surgery and 1 had a myocardial infarction before planned 6-month repeat catheterization. Two patients were lost to follow-up study. Of the remaining 62 patients, 56 (90%) agreed to follow-up catheterization and 25 (45%) of the 56 had restenosis. Thus, 30 patients had an adverse outcome and 37 had no adverse event. The incidence of dissection detected by ultrasound imaging after an intervention was significantly greater in patients with than in those without a subsequent adverse event (63% vs. 35%, p < 0.05). The severity of dissection also appeared to be related to outcome (p < 0.05). Other qualitative and quantitative variables were not significantly different between the two patient groups. CONCLUSIONS: Dissection, as assessed by intracoronary ultrasound imaging after a coronary artery intervention, can identify patients at increased risk of subsequent adverse events. Additional studies are warranted to explore whether such imaging may allow modification of interventional procedures to improve outcome. PMID- 1430690 TI - Mechanisms of spontaneous shift of surface electrocardiographic configuration during ventricular tachycardia. AB - OBJECTIVES: The aim of this study was to examine, with multichannel direct cardiac mapping techniques, the mechanisms of spontaneous shift of the QRS configuration in the surface electrocardiogram during episodes of ventricular tachycardia. BACKGROUND: Ventricular tachycardias demonstrating a spontaneous shift in their surface electrocardiographic (ECG) features are occasionally encountered. It is not known whether such changes in configuration are primarily due to a significant change in the tachycardia site of origin or represent alterations in patterns of endocardial and epicardial activation. Knowledge of these features would be helpful, particularly when ablative therapy is considered for the arrhythmias. METHODS: During map-directed cardiac surgery, episodes of ventricular tachycardia were mapped from 224 epicardial and endocardial sites. Episodes of pleomorphic tachycardia were identified and isochronal maps of endocardial and epicardial activation were constructed from representative beats before and after the change in configuration. RESULTS: From 52 consecutive patients who underwent detailed intraoperative mapping, 9 patients with pleomorphic ventricular tachycardia were identified in whom 14 episodes of spontaneous shift occurred. An analysis of the epicardial activation patterns revealed that the sites of earliest epicardial breakthrough showed significant alteration at the time of QRS shift in all occurrences. In 10 of these shift episodes, however, the sites of tachycardia origin, located on the endocardial surface, remained closely adjacent (< 2 cm apart). Although these sites of origin remained relatively constant, significant alterations in the patterns of endocardial activation were seen in most episodes. These included changes in the direction of propagation of the wave front of activation and shifts between monoregional and figure eight patterns of activation. CONCLUSIONS: In most episodes of pleomorphic ventricular tachycardia, the arrhythmia site of origin remains relatively constant. However, patterns of epicardial activation do undergo significant change and appear to be the major determinant of the QRS configuration on the surface ECG. PMID- 1430691 TI - Radiofrequency catheter ablation of incessant, medically resistant supraventricular tachycardia in infants and small children. AB - OBJECTIVES: This study retrospectively evaluates initial experience with radiofrequency catheter ablation in a group of seven infants and small children with a history of incessant, medically resistant supraventricular tachycardia. METHODS: Before attempted catheter ablation, all patients had had unsuccessful conventional medical therapy (with digoxin or propranolol, or both) and, in addition, each continued to have daily episodes of supraventricular tachycardia while taking amiodarone or a class IC antiarrhythmic agent alone or in combination. The average patient age was 10 months (range 1 to 27) and the average patient weight was 6 kg (range 3 to 13). Electrophysiologic diagnosis included reentrant supraventricular tachycardia in six patients and atrial ectopic tachycardia in one patient. RESULTS: These seven patients underwent a total of nine catheter ablation procedures. The atrial approach to ablation was employed in eight of the nine procedures. Overall, radiofrequency catheter ablation was totally successful in five of the seven patients, partially successful in one patient and unsuccessful in the remaining patient. The combination of radiofrequency catheter ablation and surgical ablation was successful in controlling tachycardia in all patients; with at least 5 months of follow-up study, no patient has had a recurrence of supraventricular tachycardia or reappearance of a delta wave. CONCLUSIONS: Surgical ablation of arrhythmogenic substrates in the pediatric age group, although rarely indicated, has been found in the past to be safe and effective. Our initial experience with radiofrequency catheter ablation in infants and small children demonstrates that this procedure is a promising nonpharmacologic therapeutic alternative to surgical ablation. PMID- 1430692 TI - Effects of quinidine on vascular resistance and sympathetic nerve activity in humans. AB - OBJECTIVES: The purpose of the present study was to test the hypothesis that intravenous quinidine, unlike procainamide, causes direct vasodilation and reflexly mediated increases in sympathetic nerve activity. BACKGROUND: Intravenous quinidine can cause significant hypotension. Animal experiments have suggested that quinidine blocks alpha-receptors and also relaxes vascular smooth muscle by a nonadrenergic mechanism. In a recent study we showed that intravenous procainamide causes peripheral vasodilation, hypotension and inhibition of sympathetic nerve activity in humans. Intraarterial procainamide, however, did not cause vasodilation. METHODS: Postganglionic muscle sympathetic nerve traffic was recorded from the peroneal nerve at the fibular head with tungsten microelectrodes, and forearm blood flow was measured with venous occlusion plethysmography. Central venous pressure was measured directly. The direct effects of quinidine on vascular resistance were determined with brachial artery quinidine infusions and measurement of ipsilateral forearm blood flow. RESULTS: In eight normal subjects intravenous quinidine (8 mg/kg body weight infused for 27 min) decreased mean arterial pressure from 87 +/- 3 (mean +/- SE) to 83 +/- 3 mm Hg, central venous pressure from 6.3 +/- 0.6 to 5.0 +/- 0.7 mm Hg and forearm vascular resistance from 32.2 +/- 5.5 to 25.3 +/- 4.7 U (all p < 0.05). Heart rate increased from 67 +/- 4 to 77 +/- 5 beats/min and muscle sympathetic nerve activity from 288 +/- 70 to 660 +/- 151 U/min (both p < 0.05). In five subjects intravenous nitroprusside that caused similar hemodynamic effects produced similar increases in sympathetic nerve activity. In eight subjects graded infusions of quinidine into the brachial artery (0.37, 0.74 and 1.48 mg/min) produced dose-dependent decreases in ipsilateral forearm vascular resistance and marked attenuation of forearm vasoconstriction caused by the cold pressor test. CONCLUSIONS: These data show that quinidine, unlike procainamide, causes vasodilation directly and, when given intravenously, is associated with baroreflex-mediated increases in sympathetic nerve activity. PMID- 1430693 TI - Myocardial washout of sonicated iopamidol reflects coronary blood flow in the absence of autoregulation. AB - OBJECTIVES: The aim of the study was to evaluate the relation between measurements derived from myocardial contrast echocardiography and coronary blood flow. BACKGROUND: Contrast echocardiography has the potential for measuring blood flow. METHODS: In six open chest anesthetized dogs, the left circumflex coronary artery was cannulated and perfused with blood drawn from the left femoral artery. While adenosine was infused into the circuit, circumflex flow was generated by a calibrated roller pump to the point of abolishing coronary autoregulation. At each of 25 levels of coronary blood flow, paired bolus injections of sonicated iopamidol were performed proximal to a mixing chamber. The perfused area of the left circumflex coronary artery was labeled by radioactive microspheres injected into the perfusion line. Two-dimensional echocardiographic images of the left ventricular short axis were digitized off-line, and myocardial videodensity was measured in the area perfused by the left circumflex coronary artery to generate time-intensity curves. RESULTS: The washout slope of curves showed a good correlation with coronary blood flow, ranging from 0.5 to 12.5 ml/min per g of tissue. This correlation was good both in individual dogs (correlation coefficient [r] ranging from 0.78 to 0.96) and in the group of animals as a whole (r = 0.85). Washout slope also showed a good correlation with coronary diastolic pressure (r = 0.80), which ranged from 23 to 114 mm Hg, suggesting a possible primary effect of pressure on contrast washout. However, coronary blood flow appeared to be a stronger predictor of washout slope (partial F = 26.5, p < 0.001) than did perfusion pressure (partial F = 5.9, p < 0.05 by multiple regression). The injection to injection variability in myocardial washout slope appeared to be high (24%). The gamma variate fitting of curves did not improve the correlation with coronary flow (r = 0.78). CONCLUSIONS: Myocardial washout of sonicated iopamidol reflects coronary blood flow in a model in which coronary autoregulation is abolished. PMID- 1430694 TI - Comparison of left ventricular cryolesions created by liquid nitrogen and nitrous oxide. AB - OBJECTIVES: This study was designed to compare the cryosurgical lesions produced by liquid nitrogen (-196 degrees C) and nitrous oxide (-76 degrees C). BACKGROUND: Cryosurgical ablation is a useful method of arrhythmia surgery, but information on the dimensions of cardiac lesions produced by modifying cryoprobe temperature is limited. METHODS: We compared the dimensions, volumes and electrophysiologic effects of cryolesions created by a liquid nitrogen cryoprobe (Group I) and a nitrous oxide cryoprobe (Group II) on the left ventricular myocardium in the beating canine heart. Exposure time was compared at 1, 2, 3 and 4 min. In each of 18 dogs, two to four lesions were created on the left ventricle and analyzed: 35 lesions created with use of the nitrous oxide cryoprobe and 30 lesions created with the liquid nitrogen cryoprobe. Lesions were measured at the time of induced death 6 weeks postoperatively and assessed by tissue staining with the Masson trichrome technique. RESULTS: The volumes (mm3) of the cryolesions created by the liquid nitrogen cryoprobe were significantly larger (p < 0.05) than those of lesions created by nitrous oxide: 826 +/- 163 versus 493 +/ 197 at 1 min; 1,101 +/- 327 versus 666 +/- 185 at 2 min; 1,356 +/- 318 versus 787 +/- 258 at 3 min and 1,735 +/- 534 versus 923 +/- 376 at 4 min. CONCLUSIONS: Decreasing the temperature of the cryoprobe by using liquid nitrogen increases the volume of the lesions. Programmed electrical stimulation before and 6 weeks after cryoablation indicated no arrhythmogenicity. PMID- 1430695 TI - Smooth muscle cell outgrowth from human atherosclerotic plaque: implications for the assessment of lesion biology. AB - OBJECTIVES: The purpose of this study was to determine whether the kinetics of smooth muscle cell outgrowth from in vitro explants of human atherosclerotic tissue is dependent on the nature of the atherosclerotic lesion in vivo. BACKGROUND: The use of techniques for percutaneous in vivo extraction of atherosclerotic plaque has provided the opportunity to study human atheroma derived smooth muscle cells in culture. However, because of cell selection and changes in phenotype, in vitro findings may not always reflect the biologic properties of the vessel wall, particularly if cells are in culture for prolonged periods. In contrast, studies with nonhuman cells have suggested that the rate at which cells grow out of tissue explants is closely related to the status of the cells in vivo. METHODS: Atherosclerotic tissue from 41 lesions, including primary plaques (from peripheral arteries and venous bypass conduits) and restenotic lesions (from peripheral arteries and venous conduits) were divided into a total of 1,596 fragments and placed in culture on fibronectin-coated wells. Explant outgrowth was scored over the ensuing 1 month to determine the prevalence and time course of smooth muscle cell outgrowth and the total cellular accumulation. RESULTS: Explant fragments from 40 (98%) of the 41 lesions yielded an outgrowth of smooth muscle cells, confirmed by immunocytochemistry. The mean proportion of adherent explant fragments yielding outgrowth, per lesion, was 69 +/- 4% and was higher in restenotic tissue (81 +/- 3%) than in primary tissue (56 +/- 6%, p < 0.001). For primary lesions, initiation of outgrowth was half-maximal by 8.7 +/- 0.4 days; for restenotic explants, initiation of outgrowth was considerably faster (half-maximal by 5.9 +/- 0.6 days, p < 0.001). Similarly, accumulation of smooth muscle cells around an explant was significantly greater for restenotic lesions (2,791 +/- 631 cells/explant) than for primary lesions (653 +/- 144 cells/explant, p < 0.01). Labeling of first-passage cells with [3H]-thymidine indicated that cells from restenotic lesions had a 1.3-fold greater incorporation rate than did cells from primary lesions (p < 0.05). CONCLUSIONS: Smooth muscle cells may be reliably cultivated by explant outgrowth from a variety of human atherosclerotic plaque types obtained intraoperatively or percutaneously. The kinetics of outgrowth from restenotic tissue is distinctly different from that of outgrowth from primary tissue, suggesting a relation between the in vitro outgrowth behavior and the biology of the lesion in vivo. Assessment of smooth muscle cell outgrowth from human atherosclerotic plaque may thus represent a practical and reliable means to investigate the biologic behavior, including growth characteristics, of individual atherosclerotic lesions from human subjects. This technique may also offer a suitable assay system for evaluating therapies designed to inhibit lesion proliferation. PMID- 1430696 TI - ACC educational programs. PMID- 1430697 TI - F-18 fluorodeoxyglucose and cardiac metabolism. PMID- 1430698 TI - Ventricular hypertrophy, diuretic drugs and arrhythmias. PMID- 1430699 TI - Allergic contact reactions in health personnel. PMID- 1430700 TI - Immediate type of allergy in statis growers. AB - Three statis growers complaining of immediate allergic symptoms induced by harvesting statis in a plastic greenhouse were examined to clarify their allergic conditions. Distinct positive reactions in the intradermal test and nasal and eye provocation test to the statis extracts were shown in all three cases. High score of radioallergosorbent test (RAST) IgE and remarkable RAST inhibitory effects to the statis extracts were seen in these cases. The immunologic cross-reactivity between statis and chrysanthemum was absent in the RAST inhibition in the patient labeled case C who had complained of the same allergic symptoms when handling chrysanthemums in the off-season for harvesting statis. Those results indicated that the allergic conditions of the present cases were from an immediate type of allergy mediated by a specific IgE antibody to the statis extract. PMID- 1430701 TI - Blood eosinophil numbers and activity during 24 hours: effects of treatment with budesonide and bambuterol. AB - The effects of the inhaled corticosteroid budesonide and the oral long-acting beta-agonist bambuterol on circadian variation of blood eosinophil numbers, serum levels of eosinophil cationic protein (ECP), serum eosinophil chemotactic activity (ECA), and serum neutrophil chemotactic activity (NCA) were studied in two groups of patients with allergic asthma. Group 1 (n = 8) had a circadian variation of peak expiratory flow (PEF) 15% or greater, and group 2 (n = 9) had a circadian PEF variation less than 15%. Both groups were randomized and crossover treated for 4 weeks with (A) 0.4 mg budesonide at 8 AM and 8 PM, (B) 20 mg bambuterol at 8 PM, and (C) placebo. At the end of each period blood eosinophil numbers, ECP, ECA, and NCA were measured during 24 hours at 4-hour intervals. No significant differences in the inflammatory parameters could be observed between the groups, although eosinophil numbers tended to be higher in group 1 than in group 2. Highest eosinophil numbers were observed at night. Budesonide reduced both eosinophil numbers and ECP levels, especially at night; bambuterol had no effect on both variables. No circadian variation or treatment effects were observed for ECA and NCA. This study suggests a role for the eosinophil in the nocturnal worsening of asthma, and it demonstrates that budesonide produces, in contrast to bambuterol, a reduction of (nocturnal) eosinophil numbers and activity. PMID- 1430702 TI - IgE and adenosine 5' triphosphate receptors on immature murine mast cells are functionally linked to signal transduction mechanisms. AB - Calcium mobilization in response to IgE-receptor cross-linking by antigen was assessed in immature murine mast cells cultured from bone marrow to determine whether the early expression of IgE receptors on such cells may be of functional significance. IgE receptors were expressed by approximately 30% of cells after 1 week in culture and by an increased proportion at 2 and 3 weeks. The ability of a non-IgE-dependent stimulus, adenosine 5' triphosphate (ATP), to increase intracellular calcium in these cells was also tested. Calcium mobilization in large numbers of individual cells was monitored with use of a fluorimetric reagent and flow cytometry. Both antigen and ATP had significant effects on intracellular calcium in cells cultured for as little as 1 week with interleukin 3, when few cells exhibited morphologic or functional characteristics of mast cells. Longer times in culture were associated with an increase in the proportion of cells responding to these stimuli with calcium mobilization, but not with a change in the magnitude of the response. We conclude that the early expression of IgE receptors during mast cell development may be functionally significant, since these receptors appear to be linked to cellular signal transduction mechanisms. The data additionally imply a possible role for ATP in mast cell development. PMID- 1430703 TI - The effect of IL-4 on human nasal mucosal responses. AB - Interleukin (IL)-4 causes the dose limiting sensation of nasal congestion when administered systematically at doses of 3 micrograms/kg or higher thrice daily to humans. This side effect was observed in a group of patients treated as part of an immunotherapy protocol for cancer management. To determine the source of this congestion, nasal secretions were collected prospectively in a group of patients at baseline and after provocation with normal saline, methacholine (which stimulates glandular secretion), and histamine (which causes increased vascular permeability). Nasal lavages obtained at baseline and after provocation were analyzed for the presence of these glandular and vascular proteins and inflammatory mediators. Washings and provocations were performed before IL-4 administration, after 24 hours of IL-4 treatment, and after 3 days of treatment, at a time when nasal congestion was maximal. Compared with histamine challenge before IL-4 treatment, the secretion of the plasma proteins albumin and IgG were significantly decreased after 3 days of IL-4 treatment. IL-4 treatment had no apparent effect on methacholine-induced responses. Thus systemically administered IL-4 causes the subjective sensation of nasal congestion, increased histamine in nasal lavages, and the development of vascular unresponsiveness to histamine, without affecting parasympathetic responses to histamine. The relationships among increases in nasal lavage histamine, vascular unresponsiveness to histamine, and the sensation of nasal congestion are unclear. PMID- 1430704 TI - Induction of granule release by intracellular application of calcium and guanosine-5'-O-(3-thiotriphosphate) in human eosinophils. AB - The roles of Ca and G proteins in granule release from human eosinophils were examined by use of a patch-clamp technique in single cells. The morphologic changes and the release of eosinophil peroxidase (EPO) from single cells were simultaneously observed. In addition, the expression of small molecular weight guanine nucleotide binding protein (small G protein) mRNA (smg p25A [rab 3] and smg p21 [rab 1]) was investigated. The intracellular application of Ca, 10 mumol/L, and guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), 100 mumol/L, induced fusion of EPO containing granules with the surface membrane, which was associated with a marked increase in membrane capacitance. Ca alone caused a rapid granule release at an early stage of cell dialysis, but most granules still remained in a cluster. GTP-gamma-S alone caused a gradual degranulation. Northern blot analysis revealed the definite expression of smg p21 mRNA with no appreciable expression of smg p25A. These results provide direct evidence of granule fusion by intracellular application of Ca and GTP-gamma-S. In addition, Ca dependent proteins and G proteins act cooperatively in granule release, and these proteins likely regulate the different processes of degranulation. Furthermore, a protein, encoded by smg p21, may be involved in the granule release process in human eosinophils. PMID- 1430705 TI - Does forced air heating exacerbate asthma? AB - Asthma morbidity increases in the Canadian autumn coincident with the beginning of home heating. To test the hypothesis that forced air heating exacerbates asthma, 51 subjects were randomly assigned to one of two groups: the intervention (off1-on2) group was instructed to keep their home forced air heating off from September 9 to 17 and then to set the thermostat to 22 degrees C from 8 PM to 8 AM between September 18 and 25. The concurrent control (off1-off2) group was instructed to keep their forced air heating off during the entire study period. Forty-eight of the 51 subjects randomized recorded morning peak flows, asthma symptoms, and bronchodilator use during the study period. For the intervention group, results before compared with during home heating, respectively, were as follows: mean nocturnal awakenings 0.36 versus 0.36; any breathing difficulties an awakening 82% versus 73%; mean morning peak flows 406 lpm versus 409 lpm, a difference of 3.3% +/- 6.7% (SEM), p = 0.6. There was a 95% probability that the true change in peak flows with forced air was less than 2%. For the control group, the comparable results were as follows: mean nocturnal awakening 0.40 versus 0.47; breathing difficulties on awakening 40% versus 47%; mean morning peak flows 400 lpm versus 399 lpm (p = 0.9). The commencement of forced air heating did not exacerbate asthma in this clinical population and is therefore unlikely to be an important problem for most people suffering from asthma. PMID- 1430706 TI - Effects of inhaled budesonide on serum markers of bone metabolism in children with asthma. AB - The effects of inhaled glucocorticoids on serum markers of bone formation were evaluated in asthmatic children. Serum total alkaline phosphatase (AP), bone alkaline phosphatase (BAP), osteocalcin, and the novel marker of bone formation, carboxypropeptide of type I procollagen (PICP), were measured. In the cross sectional part, long-term glucocorticoid users were compared with sodium cromoglycate (SCG) users. In the boys (n = 16), but not in the girls (n = 11), PICP was significantly lower in the glucocorticoid users than in the SCG users. PICP correlated positively with BAP (n = 54; groups combined, r = 0.29, p < 0.05). In the longitudinal part, the effects of inhaled budesonide or SCG, both used for the first time, were evaluated before and after 1 and 5 months of treatment. The budesonide dose was 800 micrograms/m2/day for 1 month and thereafter half of that. The SCG dose was 30 mg/day throughout the study. Only during budesonide use did osteocalcin and PICP decrease, the median osteocalcin by 8% at 1 month (p < 0.05) and by 6% at 5 months (n = 15), and PICP by 5% at 1 month (p < 0.05) and by 28% at 5 months (n = 7, p < 0.01). AP and BAP did not change significantly. Decreased PICP suggests decreased bone formation rate. PICP might be clinically useful as a marker of early adverse effects of glucocorticoids on bone. PMID- 1430707 TI - Passive cutaneous anaphylaxis in mouse skin is associated with local accumulation of interleukin-6 mRNA and immunoreactive interleukin-6 protein. AB - We used a BALB/c model of passive cutaneous anaphylaxis (PCA), an IgE-mediated, mast cell-dependent reaction, to demonstrate the early production of the proinflammatory cytokine interleukin-6 (IL-6) mRNA and protein product. Northern blot analysis detects IL-6 mRNA 1, and 2 hours after antigen challenge (dinitrophenyl30-40 human serum albumin [DNP30-40-HSA]) and in situ hybridization reveals that it is primarily cells with round-to-oval nuclei within the dermis (1 to 3 per high-power field) expressing IL-6 mRNA. Immunohistochemistry revealed perinuclear and cytoplasmic staining for immunoreactive IL-6 in mononuclear dermal cells and also cells within the basal keratinocyte layer. Injection of recombinant murine IL-6 (rmIL-6) either systemically or locally during antidinitrophenyl IgE skin sensitization resulted in increased vasopermeability at the PCA site after DNP30-40-HSA. However, this increased permeability was not associated with a change in the character of the cellular infiltrate at the PCA site 8 hours later. Although the specific role of IL-6 in the generation of the allergic response remains unknown, its detection during PCA unequivocally demonstrates that IL-6 be considered one of the mediators identified in inflammation that follows allergic reactions. PMID- 1430708 TI - Protective activity of inhaled nonsteroidal antiinflammatory drugs on bronchial responsiveness to ultrasonically nebulized water. AB - Relatively high doses of oral aspirin are needed to afford a significant protective effect against the bronchial obstructive reaction to ultrasonically nebulized distilled water (UNDW) in asthmatic patients. Sodium salicylate at similar doses and indomethacin at normal dose afford no protection. The present study was undertaken to assess the protective activity of these drugs taken by inhalation. Thirteen asthmatic patients performed two UNDW challenges 20 minutes and 24 hours after inhalation of 900 mg lysine acetylsalicylate (L-ASA) or placebo. The volume of UNDW causing a 20% fall in FEV1 (UNDW PD20) was calculated by linear interpolation on the dose-response curve. UNDW response after placebo was not significantly different from the preliminary test (PD20 4.3 +/- 0.7 and 4.1 +/- 04 ml, respectively, mean +/- SE), whereas after L-ASA, UNDW PD20 increased to 17 +/- 2.7 ml (p < 0.01 vs placebo) and remained significantly increased after 24 hours. In another group of 12 patients under the same experimental conditions, an equivalent dose of inhaled sodium salicylate caused no effect. Finally, in a third group of asthmatic patients pretreatment with inhaled indomethacin at two dose levels (6 patients, 25 mg; 10 patients, 50 mg) resulted in a significant dose-related protective effect. These findings indicate that inhaled indomethacin and especially L-ASA exert against UNDW-induced bronchoconstriction a potent protective effect, which appears to be mediated by inhibition of local prostaglandin synthesis in the airways. This fact could have therapeutic implications. PMID- 1430709 TI - The protective effect of low-dose inhaled fenoterol against methacholine and exercise-induced bronchoconstriction in asthma: a dose-response study. AB - We compared in a randomized, double-blind study the protective effect of low doses of fenoterol on the airway response to exercise during cold air breathing and an inhalation challenge with methacholine. In six asymptomatic asthmatic persons (mean age, 20.3 years) exercise and methacholine challenges were performed under control conditions and 15 minutes after the inhalation from a metered-dose inhaler of either placebo or 30, 50, 100, and 200 micrograms fenoterol, resulting in 12 separate study sessions within a 3-week period. Airway response was determined by measuring specific airway resistance (sRaw). Exercise tests were standardized by maintaining a constant respiratory heat exchange, with an average (range) of 1.28 (1.15 to 1.45) kcal/min. Methacholine was inhaled at increasing doses until sRaw had doubled (PD100sRaw). Mean postexertional increase of sRaw (SD) after control conditions, placebo, and 30, 50, 100, and 200 micrograms fenoterol aerosol was 27.8 (6.9), 28.9 (10.0), 7.20 (2.7), 9.33 (3.8), 5.57 (2.3), and 5.28 (1.6) cm H2O.s. Fenoterol aerosol was equally effective at all doses administered, whereas methacholine-induced bronchoconstriction was attenuated in a dose-dependent manner. From these observations we suggest that low-dose fenoterol protects against bronchoconstriction induced by exercise, a naturally occurring stimulus reflecting airway hyperresponsiveness. PMID- 1430711 TI - Adverse reaction to ocular cromolyn sodium. PMID- 1430710 TI - A possible role for adhesion molecules in asthma. PMID- 1430712 TI - A clinical approach to a patient with praziquantel hypersensitivity. PMID- 1430713 TI - Fat replacements: helpful or not? PMID- 1430714 TI - Bariatric Society seeks dietitian members, supports appropriate use of appetite suppressants. PMID- 1430715 TI - Obesity treatment requires flexibility. PMID- 1430716 TI - 'Happy meals' make happy patients. PMID- 1430717 TI - Profile of blacks employed in dietetics and nutrition. PMID- 1430718 TI - Comparison of body mass indexes and cutoff points for estimating the prevalence of overweight in Hispanic women. AB - The anthropometric standards used for estimating the prevalence of overweight among Hispanic groups are generally developed in other populations. Our purpose was to identify appropriate anthropometric indicators and cutoff points for Hispanic women. Data from the Hispanic Health and Nutrition Examination Survey HHANES (1982-1984) included 1,784 Mexican American, 479 Cuban American, and 750 Puerto Rico women aged 25 to 74 years. The body mass indexes examined were weight/standing height1.5, weight/standing height2, weight/sitting height1.5, and weight/sitting height2. Appropriateness was based on correlation of the index with triceps and subscapular skinfold measurements and lack of association with standing or sitting height. The most appropriate indicator was weight/standing height2. To estimate overweight, the 85th percentiles for weight/standing height2 were obtained from the 20- to 29-year-olds in HHANES and the second National Health and Nutrition Examination Survey (NHANES II). For 10-year age intervals, the differences in proportions of women above those cutoff points were compared with a modified t test. The mean estimated prevalences of overweight were significantly higher with the NHANES II standard compared with the HHANES cutoff points (P < .05) for Mexican American women (43% vs 29%) and Puerto Rican women (40% vs 28%). They were slightly lower for the Cuban American women (36% vs 39%). Cutoff points are relative, not absolute, standards that must have biologic meaning. Before our results are used for assessing populations, the cutoff points should be tested for predictive validity with chronic disease rates. PMID- 1430719 TI - Determinants of weight gain in pregnant adolescents. AB - Maternal weight gain is the most important modifiable determinant of infant birth weight. Effective intervention requires an understanding of the factors that influence the amount of weight women gain during pregnancy. We studied the dietary, health, and social habits of 141 poor, black, 12- to 19-year-old prenatal patients to learn more about the determinants of weight gain among pregnant adolescents. The patients were divided into three weight gain groups: slow (n = 23): less than 0.28 kg/week; average (n = 87): 0.28-0.45 kg/week; and rapid (n = 31): more than 0.45 kg/week. The results of logistic regression analysis revealed two statistically significant predictors of slow weight gain: the consumption of fewer than three snacks per day and delayed (third trimester) enrollment in the Supplemental Food Program for Women, Infants, and Children. By contrast, rapid gainers were more compliant with prenatal visits and reported more depressive symptoms and alcohol consumption than did other study subjects. We conclude that attention to these modifiable correlates of inadequate and excessive weight gain may enable dietitians and other health care providers to develop more effective strategies for promoting optimal weight gain among pregnant adolescents. PMID- 1430720 TI - Demographic and economic factors associated with dietary quality for adults in the 1987-88 Nationwide Food Consumption Survey. AB - Data for 5,884 adults (19 years of age and older) who participated in the 1987-88 Nationwide Food Consumption Survey (1987-88 NFCS) were used to investigate demographic and economic factors associated with dietary quality. Although the low response rate for the 1987-88 NFCS has raised concerns about possible bias, it is appropriate to use this extensive data set for analyses that do not attempt to generalize the results to the US population as a whole. Two aspects of quality were calculated for the mean of the 3-day reported intakes: number of nutrients below two thirds of the 1989 Recommended Dietary Allowance (RDA) (low-intake nutrients) and percent of energy from fat. Few adults reported mean intakes that met suggested guidelines: 22% of diets were above two thirds of the RDA for all 15 nutrients and 14% were below 30% fat, but only 2% met both criteria. Energy intake was a strong negative predictor of number of low-intake nutrients and a weak positive predictor of percent of energy from fat. Results of multivariate regression analyses identified few demographic or economic predictors of either the number of low-intake nutrients or percent of energy from fat. According to these data, diets of most adults do not conform to current dietary guidelines. Nutrition education efforts should be directed to all adults, and research should be undertaken to determine more effective ways to help adults improve their overall dietary quality. PMID- 1430721 TI - Development and preparation of lean meat products. AB - When the effect of food on human lipoprotein levels is tested, or when human consumption of dietary lipids must be controlled or limited, all food needs to be provided under controlled conditions to achieve consistent composition and sensory traits. It is especially important to control the composition of foods, particularly fat and fatty acid content. Because of the inherent biologic variability in the chemical composition of animal tissues (beef in particular), raw materials must be selected carefully and prepared under strict guidelines. In addition, chemical composition should be verified initially and during the production of the product to ensure the accuracy necessary for controlled dietary intake. Furthermore, the meat provided must be easy for the study subject to prepare, be of consistent serving size, and yet be highly palatable to maintain the subject's interest and participation. This article outlines the protocol for developing lean meat products for use in nutrition studies in which fat content must be controlled, especially those studies designed to examine the effect of fat content on human lipoproteins. Preliminary studies, procurement of raw materials, procedures for recipe selection, product preparation, and sampling procedures for verification of chemical composition are described. Our findings indicate that fat intake from beef, chicken, and fish can be controlled for use in nutrition studies. PMID- 1430722 TI - Nutrient composition and sensory attributes of cooked ground beef: effects of fat content, cooking method, and water rinsing. AB - Ground beef with 10%, 20%, and 30% fat was shaped into patties or crumbled and cooked by panfrying, panbroiling, or microwaving. After cooking, half of the crumbles were water rinsed. Samples were analyzed for yield, energy, moisture, protein, total lipid, cholesterol, iron, and zinc. In other experiments, cooked crumbled samples were analyzed for vitamin B-12 content and sensory qualities. Effects of cooking method on total lipid and cholesterol levels were generally small. Initial fat level significantly affected total lipid content in cooked ground beef; cooked samples with 10% initial fat contained slightly less total lipid than those with 20% or 30% initial fat. Rinsing with warm water significantly reduced fat and increased the moisture content of cooked ground beef crumbles. Protein, iron, zinc, and vitamin B-12 were well retained during rinsing. We conclude that consumers can achieve a significant reduction in fat content, without substantial losses in protein, iron, zinc, or vitamin B-12, if they water rinse cooked ground beef crumbles. The flavor and texture of the cooked ground beef crumbles are altered somewhat by rinsing. Acceptance in mixed recipes was not determined. PMID- 1430723 TI - Consumption of a dehydrated ration for 31 days at moderate altitudes: status of zinc, copper, and vitamin B-6. AB - Intake of energy zinc, copper, and vitamin B-6 and indexes of zinc, copper and vitamin B-6 status were determined for eight men who consumed a high-carbohydrate dehydrated ration for 31 days of high activity at moderate altitudes (2,400 to 4,300 m). Data were collected 2 months before exposure (PRE), four times during the month at moderate altitudes (ALT), and 1 month after return (RET). Mean (+/- standard error) energy intake was 2,725 +/- 215, 3,430 +/- 79, and 3,370 +/- 215 kcal/day during PRE, ALT, and RET, respectively. Zinc and copper intakes averaged 10.6 +/- 1.6 and 1.0 +/- 0.1 mg/day during PRE and increased significantly to 16.9 +/- 0.7 and 3.5 +/- 0.1 mg/day during ALT; zinc and copper intakes were 15.5 +/- 1.6 and 1.9 +/- 0.3 mg/day for RET, respectively. Similarly, vitamin B-6 intake was significantly higher during ALT (PRE = 2.2 +/- 0.5 mg/day; ALT = 4.2 +/- 0.4 mg/day; and RET = 2.6 +/- 0.4 mg/day) as compared with PRE and RET. No significant changes were noted for plasma zinc, copper, or their related proteins or plasma or erythrocyte pyridoxal-5'-phosphate. Finally, no changes in urinary excretion of zinc were observed. The results indicate that dehydrated rations provide zinc, copper, and vitamin B-6 in amounts above the Recommended Dietary Allowances. Such diets may be consumed for at least 1 month without compromising status for these nutrients. PMID- 1430724 TI - Participation in a worksite cholesterol education program in a university setting. AB - Three hundred ninety-six employees of a large northeastern university participated in a blood cholesterol screening and provided follow-up data about their participation in a videotape cholesterol education program. Ten percent of these employees watched the videotape program; these individuals were significantly more likely to be at high risk for cardiovascular disease than were persons who chose not to watch the videotape. Persons participating in the cholesterol education program significantly increased their nutrition knowledge and significantly decreased their fat intake compared with nonparticipants. The most important reason given for watching the videotape was "concern about my cholesterol level." Reasons given for not watching the videotape were that it was "not well advertised" or that it was shown "at an inconvenient time." Although all 98 employees at high risk for cardiovascular disease were referred to their physicians for diagnostic evaluation, one third of these employees reported not seeing their physicians. These findings indicate that worksite cholesterol screening and education programs can improve nutrition knowledge and dietary behavior; however, these programs should develop strategies to increase participation and should follow up physician referrals. PMID- 1430725 TI - Worksite nutrition education can lower total cholesterol levels and promote weight loss among police department employees. AB - Individuals who work in law enforcement careers are often subjected to stress that can result in health and emotional disorders. Many police departments have begun to offer wellness programs to support their employees. This pilot study designed and implemented a nutrition education component for an existing police department wellness program. Twenty-eight subjects completed the 12-month study that included nutrition counseling, seminars on nutrition and eating behaviors, and monitoring of weight and blood lipid levels. There was a significant group trend for decreased weight and lower total cholesterol levels. Results of the study led to the development of health policy standards for the Austin (Tex) Police Department. Wellness programs that involve registered dietitians can result in weight loss and lower cholesterol levels for employees in high-stress occupations as well as changes in departmental policy. PMID- 1430726 TI - Reimbursement for clinical nutrition services: a 10-year experience. AB - Charges for nutrition products and services grew more than 800% between 1980 and 1990 at Children's Memorial Medical Center, Chicago, Ill. Three factors contributed to the growth in charges: distinguishing special services from those included in the bed charge, requiring rigorous documentation of services ordered and provided, and building administrative support for the program. Of the charges, 91% were related to nutrition support. The hospital converted 99% of the charges to private payers into actual revenue. The charge program provides the structure, discipline, and data to demonstrate the value of nutrition services for improving patient outcomes and may help sustain financial support even if the health care industry continues to move away from direct payment for services. Charging for nutrition products and services is a useful way for dietitians to document and be compensated for the value of their services in a hospital setting. PMID- 1430727 TI - Feeding strategy for dependent eaters. PMID- 1430728 TI - Comparative evaluation of four microcomputer nutrient analysis software packages using 24-hour dietary recalls of homeless children. PMID- 1430729 TI - Usefulness of various maternal skinfold measurements for predicting newborn birth weight. PMID- 1430730 TI - Caliper method vs bioelectrical impedance analysis for determining body fat in patients undergoing chronic dialysis and in healthy individuals. PMID- 1430731 TI - Kathleen Keen Zolber, PhD, RD, receives 1992 Copher Memorial Award. PMID- 1430732 TI - Setting the standards for passing the registration examinations. PMID- 1430733 TI - The Senate, obscenity, and the First Amendment. PMID- 1430734 TI - 1992--the year of the woman. PMID- 1430735 TI - Political pearls. PMID- 1430736 TI - Hormone replacement therapy: decision making in an age of uncertainty. AB - The burgeoning epidemic of breast cancer has led to further scrutiny of the relationship between it and estrogen replacement therapy. While, according to multiple analyses, the relative risk of breast cancer in estrogen users seems to be only slightly increased over 1.0, the risk is not evenly distributed among various populations of women. In clinical practice, doctors are not certain which of their patients are prone to develop breast cancer and which are not. Still, the physician confronts the need to make practical decisions about hormone administration. A decision tree is presented in this paper to facilitate the choice and to help the practitioner in reconciling two seemingly contradictory medical precepts. PMID- 1430737 TI - African-American women who always use condoms: attitudes, knowledge about AIDS, and sexual behavior. AB - Given the alarming increase in the incidence of sexually transmitted diseases (STDs), including AIDS, among African-American women, it is apparent that many people are engaging in sexual intercourse without using condoms. The current study examined the interrelationships among attitudes about condom use, knowledge about AIDS, sexual behavior, and drug use among 121 adult African-American women who varied in their intentions to use condoms: 21 (17%) were classified as Steady Users, 75 (62%) did not use condoms but they had High Intentions to, while 25 (21%) did not use condoms and had Low Intentions to use them. Results indicate that the three groups did not differ in their overall knowledge about AIDS or their attitudes toward using condoms as contraceptives. Significant group differences were noted for other scales that assessed attitudes about condoms. Attitudes about the use of condoms were very similar for the Steady Users and the women in the High Intentions group. However, these two groups were significantly (p < .01) different in their belief that condoms are uncomfortable and interrupt sex. Women with Low Intentions to use condoms had significantly (p < .05) more intense angry reactions regarding the negotiation of condom use and significantly more negative attitudes about the use of condoms than women in the other groups. The three groups were not differentiated by drug use, previous treatment for STDs, or their perceived risk for being exposed to AIDS. The present study is cross-sectional in nature and future research using better methodology is needed to establish causal relationships. PMID- 1430739 TI - Seeing through the patient's eyes. PMID- 1430740 TI - The role of optometrists in dealing with patients suffering from visual impairments. PMID- 1430738 TI - Physicians and the treatment of domestic violence. PMID- 1430741 TI - Exploring the optometric application of expert computer systems. PMID- 1430742 TI - Vision problems at video display terminals: a survey of optometrists. AB - One thousand three hundred seven optometrists responded (25.3 percent response rate) to a mail questionnaire concerning VDT patients in their practice. On the average, 14.25 percent of optometric patients present with symptoms primarily associated with use of the VDT, or almost 10 million examinations annually when projected to the U.S. population. A majority (55.3 percent) reported that their VDT patients have symptoms that are different than other near point workers, especially as related to glare, lighting, unique viewing conditions and spectacle requirements, and the greater frequency and severity of symptoms. They judged that they were unable to arrive at a confident diagnosis and treatment plan for 20.87 percent of VDT patients, which was significantly more than the 14.05 percent for non-VDT patients. Uncorrected refractive errors, accommodative disorders, irritated eyes, binocular vision disorders, and spectacle design problems were the most frequently cited diagnoses. On the average, 39.3 percent of their VDT patients receive a special VDT prescription or spectacle design that is different than they would require for other daily activities. They judged that 36.8 percent of the symptoms were related to visual environmental factors, primarily glare, lighting, screen resolution and work arrangement. The best way to resolve symptoms for VDT workers is to provide thorough vision examination and treatment in conjunction with diagnosis and treatment of visual environmental problems. PMID- 1430743 TI - Specialty differentials, limited license practitioners, and Medicare's new fee schedule. AB - The use of specialty differentials in the newly adopted Medicare fee schedule has been debated over the past 2 years. Arguments supporting the elimination of specialty differentials for optometrists and ophthalmologists are presented. The first recommendations by the Physician Payment Review Commission eliminating specialty differentials represent a victory for optometry in its efforts to achieve parity in the reimbursement of Medicare-covered services. Relative value units and practice costs to be used by the new Medicare fee schedule must be determined for optometry. Estimates of the model fee schedules for eye care procedures have been released by the Department of Health and Human Services. PMID- 1430744 TI - Visuo-spatial discrimination and mirror image letter reversals in reading. AB - This review compares visuo-spatial and linguistic mechanisms for discriminating between mirror image letters. The conclusion is drawn that both processes play a role in efficient reading, their relative contributions varying with reading experience and ability. It is shown that arguments used to reject visuo-spatial theories in mirror image letter reversals are flawed. Attention is drawn to the importance of visuo-spatial discrimination of mirror image letters, based on confident left/right body awareness, for beginning readers and for older children who are deficient in compensatory linguistic skills. When confused left/right body awareness is found in association with reversal problems, there is an indication to provide remediation that includes the promotion of mirror image letter discrimination based on confident left/right body awareness. Early intervention (pre-school and infants class) programs that teach left/right body awareness as a pre-reading skill are justified when the progress of beginning readers is facilitated and the need for remedial intervention is reduced in later years. PMID- 1430745 TI - Attitudes about women in optometry. AB - A survey was conducted to examine attitudes that affect women in optometry. Most respondents felt that women have greater difficulty than men entering private practice. On the other hand, the majority felt that female optometrists do not find it more difficult to be employed by other ODs, MDs, or to work in corporate settings, HMOs/health institutions, or academic settings. Examining the results of the survey can help establish programs of professional development that will enable women to practice in the environments that they find most suitable. In addition, an open and honest discussion of these issues can raise the sensitivity of the optometric community to these issues. PMID- 1430746 TI - Using the Wayne Saccadic Fixator to evaluate aspects of laterality skills in children. AB - The Wayne Saccadic Fixator has been used to evaluate various performance characteristics of a subject's eye-hand coordination, visual reaction times, peripheral awareness, and saccadic eye movement skills. The purpose of this investigation was twofold: first, to establish standard performance scores for normal achieving children using the Wayne Saccadic Fixator preprogrammed procedure #3. The procedure was structured to compare the scoring ability of a child's dominant and non-dominant hands. The second purpose was to determine if the instrument could be used to identify children who were diagnosed by other testing methods as having laterality/directionality deficits. The data collected indicated that there was a direct relationship between age and scoring ability on this Wayne Saccadic Fixator task. However, both the normal achieving students and the special education children scored equally well when using either their dominant or non-dominant hand. There appeared to be no significant difference in the mean scoring ability of children with a diagnosed laterality deficit and children with normal laterality/directionality skills. PMID- 1430747 TI - Visual disorders of higher cortical function. AB - Following stroke or other causes of brain damage, patients may demonstrate visual disorders of higher cortical function. These defects involve visual attention, oculomotor skills, visuospatial orientation and object recognition. It is important for optometrists to understand these conditions and consider their presence in individuals with persistent visual complaints despite a normal exam, or in patients who fail to respond to magnification in low vision rehabilitation. The diagnosis and management of these higher order visual disturbances are discussed. PMID- 1430748 TI - Pupillary dilation: an eye-opening problem. AB - Dilation of the pupil is a procedure with both clinical and legal ramifications. Optometrists must be familiar with the requirements of informed consent, which must be met when utilizing dilation on the 4-8 percent of patients with anterior chamber angles that are narrow enough to cause an angle closure. Optometrists also must recognize those circumstances under which pupillary dilation is necessary, both for symptomatic and asymptomatic patients. The correct drug regimen must be selected, whether it is for "routine" pupillary dilation or for a patient with a condition requiring a special drug regimen. Patients with dilated pupils must be appropriately managed, and failure to warn a patient of common and expected side effects may create liability if the failure to warn is the cause of injury. If complications--such as acute angle closure--occur, the optometrist must be prepared to manage the situation so as to minimize the risk of injury to the patient. PMID- 1430749 TI - The Collaborative Ocular Melanoma Study. PMID- 1430750 TI - Affirmative action issues within optometry. PMID- 1430751 TI - Accommodative response during distance optometric test procedures. AB - The control of accommodation is an essential requirement during the clinical optometric assessment of distance vision. Accordingly, the aim of the present study was to examine the steady-state accommodative response during a number of conventional clinical procedures carried out at a viewing distance of 6m (20 feet). Accommodation was measured subjectively to Snellen letters using a Hartinger coincidence optometer during distance viewing, simulated retinoscopy and following the introduction of cylindrical and prismatic lenses in 13 visually normal, young adults. No significant change in the mean accommodative response was induced by any of the techniques described, with subjects exhibiting a lead of accommodation of approximately 0.25D for all conditions. The results demonstrate the robustness of accommodation to apparently substantial changes in stimulus conditions. PMID- 1430752 TI - Frequency of certain urgent eye problems in an emergency room in Massachusetts. AB - The frequency and cost of emergency room care for certain ocular problems was surveyed. Superficial eye problems accounted for 2.67 percent of patients reporting to the emergency room, while 0.23 percent reported for penetrating injuries. Of the conditions surveyed, conjunctivitis was the most commonly presenting diagnosis. Abrasions and superficial foreign bodies were the next most common presentations. Together these three diagnoses accounted for nearly 75 percent of all superficial eye problems seen in the emergency room. The cost of each emergency room visit averaged $132. This study has implications for health care managers and for legislatures contemplating expanding the scope of optometric practice. PMID- 1430753 TI - Penetrating injury from hammering with subtle ocular damage. AB - Penetrating ocular injuries are usually associated with major disruption of the globe and vision loss. On occasion, the signs and symptoms accompanying an intraocular foreign body can be subtle. Such a case is presented in this paper and hammer injuries as a cause of penetrating ocular injury are reviewed. PMID- 1430754 TI - Health care rationing in the United States: are we there yet? AB - Given the skyrocketing costs of health care in the United States, some experts propose official health care rationing as a solution to the crisis. Others maintain the position that health care is already being rationed because of cost, and always has been. This paper presents evidence supporting both viewpoints and, by exploring two definitions of "rationing," shows that they are not mutually exclusive. Practical applications to optometry as a health profession are mentioned. PMID- 1430755 TI - Increased occurrence of exfoliation in the male, Spanish American population of New Mexico. AB - Exfoliation syndrome was found to occur much more frequently in the male Spanish American population of New Mexico. This was based on a Veterans Administration Medical Center study in Albuquerque, New Mexico. The prevalence of exfoliation in the Spanish Americans was estimated to be from 3-6 percent and this is consistent with many other such studies performed in the United States and other countries. The Spanish American population is 5.8 times more likely to develop exfoliation than the non-Spanish American population of New Mexico. Exfoliation was found on such eye structures as the lens, iris, ciliary processes, posterior capsule, vitreous face, posterior corneal surface, and arterial chamber angle. Glaucoma capsulare was also studied and it was found that there was not a significant difference between the Spanish American and the non-Spanish American population for developing the condition. However, there was a strong association of glaucoma with the presence of exfoliation in both groups. Based on our results, patients with exfoliation are 22 times more likely to develop glaucoma than are their age matched controls. Also, 40 percent of the exfoliation patients had glaucoma compared with only 5 percent of the age-matched controls (p less than .001). The patients with glaucoma capsulare were found to have a more medically resistant type of glaucoma, which was consistent with other reports of this condition. There are two theories we propose for the existence of exfoliation in the Spanish American population of New Mexico. The first is a geographic climatic theory that relates exfoliation to greater solar radiation levels due to a high overall altitude and sunny weather in New Mexico.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430756 TI - Aiding the novice practitioner in contact lens selection. AB - A comprehensive study was performed to assist the new graduate and novice contact lens practitioner in the choice of the optimal lens for each case scenario, as well as provide guidance for inventory selection. The survey was distributed to the clinical staff at the State University of New York, State College of Optometry, in order to take advantage of the knowledge of the experienced contact lens fitter. There appear to be clinically significant relationships between lens characteristics and performance ratings. PMID- 1430757 TI - Paranoid character and the intolerance of indifference. AB - This paper suggests that aspects of paranoid character are structured around fantasies of magical and concrete connectedness to objects; these fantasies serve to avoid the terrors of object inconstancy. The authors describe how these fantasies are expressed in the psychoanalytic situation and explore their relation to common paranoid phenomena. The paranoid person must maintain these fantasies of connectedness at all cost or risk experiencing unbearable indifference between self and object. Paradoxically, the sacrifice of self and object boundaries inherent in these fantasies makes object constancy even more difficult to achieve because of the secondary defensive use of anger mobilized to protect the boundaries of the self. PMID- 1430758 TI - Psychoanalytic theory and its relation to clinical work. AB - Freud's shift to the fantasy theory of neurosogenesis defined the investigation of intrapsychic life as our fundamental theoretical purview. In assigning to inner experience a data base for scientific exploration, there is reflected a central epistemological innovation which must profoundly alter the way we view what is real. This paper considers some of the continuing clinical challenges and far-reaching implications posed by this shift to "psychic reality" as our core psychoanalytic theory. PMID- 1430759 TI - The concept of the therapeutic alliance. AB - Certain conceptual aspects of the therapeutic alliance are considered. Although therapeutic alliance, transference, and the real relation are intermingled and intertwined in the actuality of the analytic relationship, they remain distinguishable and open to differentiating analysis. The distinctions between the therapeutic alliance and transference, and between alliance and the real relation, are explored and their differences clarified, including the difference between therapeutic misalliances and transferences. Some of the component dimensions of the therapeutic alliance are explored, including empathy, the therapeutic framework, responsibility, authority, freedom, trust, autonomy, initiative, and ethical considerations including values and confidentiality. Further exploration of these and other dimensions of the therapeutic alliance is called for, especially the extension of these dimensions to their practical clinical application. PMID- 1430760 TI - Recurring thoughts on unconscious ego resistances. AB - Analysis of the unconscious ego resistances is one of those clinical concepts more honored in the breach than in the observance. This same point has been made periodically over the past fifty years. It has not been sufficiently realized that a true psychoanalytic understanding of resistance analysis could only begin with Freud's second theory of anxiety. Freud himself never fully embraced this theory, and clinical contributions since then have varied in their ability to use the techniques inherent in the second theory of anxiety. Recent contributions to the literature have not eliminated the espousal of theories of resistance based on earlier views of anxiety. Reasons cited for this include: the ambiguities in Freud's writing, the direction of the early ego theorists, and proclivities toward deeper interpretations. PMID- 1430762 TI - Connectivity and condensation in dreaming. AB - Converging developments in the cognitive- and neurosciences have brought Freud's hope of a bridge between psychoanalysis and psychophysiology nearer to hand. This paper concerns the relation between dream construction and memory in terms of these new developments. The neural network architecture of memory structures in the brain is described and illustrated with simple examples. We see how a network is connected and how connection weights vary with experience. The distributed representation stored by the network and its crucial properties for mental functioning are discussed. These concepts are used to explain how particular memories of past events are selected for inclusion in the dream. The properties of the neural network suggest that images of distinct past events are conflated at times during the selection process. The appearance of these conflated images may complicate the matching of day residues with representations of past events in the dream itself. Some likely implications for psychoanalytic theory are explored. PMID- 1430761 TI - The absence of the father. AB - The author discusses the role of the father in early development through the concept of triangulation. Three male patients are presented who seemed to lack images and memories of their fathers and experienced them as absent, despite their physical presence during childhood. In these men, the oedipal phase appeared skewed and a dyadic relationship with the mother dominated the material. They reported a lack of a sense of masculinity and a phobic concern about the dangers of male violence, along with feelings of specialness and grandiosity. Analytic data suggested that the image of an absent father reflected a process akin to splitting of the ego, in which the significance of the father was disavowed and the patients fantasized a special role with their mothers; via projection, the fathers reappeared as dangerous intruders. It is proposed that this structure derives from a specific developmental situation in which a disturbed parental relationship has impaired the father's position as a "third" in the early triangle. The child's sexual and aggressive tensions cannot be contained in his fantasies of the couple and must be projected outside. The absent father returns in the transference, where the analyst is reexperienced as useless and absent and as a threat to the specialness of the dyad, thereby recapitulating the predicament of the child. PMID- 1430763 TI - Acting up and physical illness: temporal patterns and emerging structure. AB - Many psychoanalytic writers have viewed acting out and somatization as alternate routes for the discharge of uncontained aggressive impulses in borderline patients. In order to investigate this empirically, we tracked the occurrence of two related behaviors--acting up and physical illness--over the course of one patient's long-term hospitalization. Daily scores on these variables were analyzed using a time series procedure. Results indicated that as treatment progressed, acting up and physical illness became more synchronized, and this occurred just prior to symptom remission. Material from psychotherapy suggested that these behavioral changes were associated with the patient's increased ability to verbalize aggressive impulses in the context of fantasy and memory. PMID- 1430764 TI - Psychoanalytic training today. AB - Psychoanalytic education in the United States faces multiple challenges as we enter the last decade of this century. (1) Changing interest and career path patterns for psychiatrists have resulted in fewer medical applications for psychoanalytic training. (2) Increased opportunities for full psychoanalytic training of nonphysicians have resulted in increased applications from highly skilled clinicians who often have more clinical experience than their medical colleagues. (3) Increased enrollment of women candidates has required rethinking of progression requirements, in light of their combined careers as professionals and mothers. (4) Independent institutes not accredited by the American Psychoanalytic Association compete for applicants while maintaining training standards that require less time and immersion in psychoanalytic theory and practice. (5) Economic factors increasingly influence the desirability of prolonged psychoanalytic training and the availability of suitable analysands for control analyses. (6) Evolution of theory and practice and the emergence of "new schools" of psychoanalytic thought have rendered the previous psychoanalytic landscape dominated by drive theory and ego psychology more multifaceted and less uniform. The American Psychoanalytic Association and its institutes attempt to understand these changing patterns and take them into consideration in the design and implementation of psychoanalytic training programs. Only one aspect of this complex situation will be described in this work, the current state of psychoanalytic training in the 28 institutes accredited by the American Psychoanalytic Association. Although the data available at this time leave unanswered many important questions about the philosophies that organize the content and emphases of the curriculum in different institutes, much has been learned about the overall structure of psychoanalytic training programs. PMID- 1430765 TI - Interactional paradigms and the self in psychoanalysis. PMID- 1430766 TI - On enactment. PMID- 1430767 TI - A possible hereditary factor in the Isakower phenomenon. PMID- 1430768 TI - Why did Freud drop the theme of group psychology? PMID- 1430769 TI - Psychoanalysis' resistance to new ideas. PMID- 1430770 TI - "Incest--see under Oedipus complex": the history of an error in psychoanalysis. AB - This paper is intended as a contribution to the understanding of errors in our field. The title refers to the index entries "incest" in several classic psychoanalytic texts. In a way that is analogous to the defenses utilized by survivors of incest, psychoanalysis has both known and not known, avowed and disavowed, the traumatic impact of actual incest. It is argued that psychoanalysis erred in (a) focusing too heavily on the implications of incest for the Oedipus complex instead of its implications for every stage of development, and (b) missing out on the full and detailed description of the clinical pictures of incest victims and of treatment issues, including transference and countertransference. The author presents an overview of the history prompted by Masson's original attack on Freud for abandoning the "seduction hypothesis." Topics covered are: Freud's early papers, the Freud Ferenczi controversy (1932), and the state of psychoanalytic awareness in the 1960's of the importance of actual incest. Certain features of our field make it all too likely that new errors can be generated that may similarly take decades to recognize and undo. These include the politics of our discipline, and negative attitudes toward systematic gathering and assessment of evidence. PMID- 1430771 TI - Neutrality, interpretation, and therapeutic intent. AB - Neutrality is a central concept within the theory of psychoanalytic technique. We spell out the major controversies in which the concept has become embroiled, and provide a definition that we believe coincides with actual psychoanalytic practice. We discuss its merits and weaknesses, noting also the negative consequences of relying on older definitions. We relate neutrality to the interpretive process, indicating ways interpretation protects neutrality and is made more effective by it. We discuss the complex and controversial relation between neutrality and the analyst's therapeutic intent. PMID- 1430772 TI - In vivo evaluation of airway and pulmonary tissue response to inhaled methacholine in the rat. AB - The current study was designed to assess the methacholine dose-response behaviour of the airways and pulmonary parenchyma with the aid of alveolar capsules. The experiments were performed in eight adult female Wistar rats (155-250 g). The animals were anaesthetized with sodium pentobarbital (30 mg kg-1 i.p.) and mechanically ventilated. Measurements of tracheal (ptr) and alveolar (pA) pressures and the pressure change across the airway (p(aw)) were performed prior to and after exposing rats to aerosols generated from sequentially increasing concentrations of methacholine chloride solution (2, 4, 8, 16, 32, 64 and 128 mg ml-1) through the breathing circuit. Baseline p(aw) and pA mean (+/- SD) values (6.44 +/- 2.06 and 8.25 +/- 3.44 cmH2O, respectively) were not statistically different (P = 0.220). The increases in ptr and pA were significant during the dose-response study (P = 0.001), whereas p(aw) was not increased. The increase in pA was significantly higher than that of p(aw) (P less than 0.001). The relationship between the mean (+/- SE) values of ptr and pA could be well described by a straight line (r = 0.990, P less than 0.001). There were also significant correlations based on regression equations between ptr and p(aw) (r = 0.947, P less than 0.001) and pA and p(aw) (r = 0.913, P = 0.004). These findings suggest that the pulmonary tissue of rats is a major component responsible for the increase in lung impedance observed after methacholine challenge. In addition, airway and pulmonary parenchyma pressure changes were correlated, suggesting that both lung regions have a similar sensitivity to the agonist. Our results indicate that the response of peripheral tissues should be considered during bronchial challenge protocols in rats. PMID- 1430773 TI - Toxicology of carbaryl and aldicarb on brain and limb cultures of chick embryos. AB - A variety of carbamates have been developed since the 1960s for use as broad spectrum insecticides. An easy and inexpensive in vitro assay using chick-embryo derived cells was examined for its capability to screen and test the toxicity of these compounds. Chick embryo brain and limb bud cultures were treated with different concentrations of either carbaryl or aldicarb with or without activation (+/- S-9) for 5 days. Viability and cytotoxicity using the neutral red assay, and carbamate effects on cell migration and colony spread were measured. S 9 decreased the effects of carbaryl and aldicarb on brain cell cytotoxicity at exposures of 15-60 ppm and 40-200 ppm, respectively, as indicated by increased concentrations of neutral red. Viability of brain cell cultures was not altered by aldicarb, but was decreased by carbaryl plus S-9 in concentrations of greater than 40 ppm. In limb cultures, carbaryl without S-9 was significantly toxic at 8 25 ppm, but only concentrations of greater than 25 ppm of carbaryl plus S-9 significantly affected cytotoxicity. In contrast, aldicarb without S-9 caused no effect on limb cell cytotoxicity at concentrations of 40-200 ppm, but aldicarb plus S-9 significantly reduced cellular cytotoxicity at concentrations of greater than 160 ppm. Carbaryl +/- S-9 decreased the spread of both brain and limb colonies; aldicarb +/- S-9 caused a significant increase in the spread of the brain but not limb colonies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430774 TI - The effect of a commercial 2,4-D formulation on chemical- and viral-induced tumor production in mice. AB - Male CD-1 mice were exposed to a commercial formulation of 2,4 dichlorophenoxyacetic acid (2,4-D), the amine derivative, in the drinking water at concentrations ranging from 0 to 0.163% of the formulated product, equivalent to approximately 0-50 mg kg-1 day-1 2,4-D content. The effect of 2,4-D on urethan induced pulmonary adenoma formation was evaluated following a 105-day exposure. Urethan-induced sleeping times observed following an i.p. injection of urethan (1.5 mg g-1) after 3 weeks of 2,4-D exposure were not altered by 2,4-D, indicating that 2,4-D did not influence urethan elimination. Pulmonary adenoma production, which was evaluated 84 days after urethan injection, was enhanced by 2,4-D exposure but had no effect on tumor size. The effect of 2,4-D on the incidence of spontaneous murine lymphocytic leukemia was evaluated during the 365 day treatment period. Mortality associated with the leukemia virus was not altered by 2,4-D treatment. Exposure to this commercial 2,4-D product at moderately high levels of exposure may modify the development or expression of certain tumors in CD-1 mice. The mechanism of the co-carcinogenic or tumor promoting activity associated with 2,4-D exposure remains to be determined. PMID- 1430775 TI - Incidence of residual levels of organophosphorus insecticides in farm produce in the Region of Murcia, Spain. Comparison of intake in the 1985-86 and 1989 campaigns. AB - We calculated the effective dietary exposure to 20 organophosphorus insecticides in a sample of residents of the Region of Murcia (Spain). Calculations were based on the contamination of 2310 specimens of citrus fruits, pitted and seedy fruits and vegetables collected in the 1985-86 and 1989 campaigns. A comparison of the results from the two campaigns showed that the mean annual insecticide ingestion determined from the mean consumption of each type of farm produce fell from 7.82 mg to 5.55 mg over the 4-year period studied. The total annual ingestion of insecticides during the 1985-86 and 1989 campaigns was ca. 0.133 and 0.1 mg kg-1 body weight; these values are well below the admissible annual ingestion of 29.565 mg kg-1 body weight. PMID- 1430776 TI - Development and validation of a high-performance liquid chromatographic method for the determination of benzophenone-3 in rats. AB - A precise, accurate, selective and sensitive liquid chromatographic method for the determination of benzophenone-3 in rat biological fluids and different tissues has been developed. The minimum detection limit for benzophenone-3 was 2.0 ng ml-1 and the retention time was 6.01 min. Standard curves for benzophenone 3 were linear in a wide range of concentrations in methanol and different body fluids, ranging from 6.25 ng ml-1 to 100 micrograms ml-1. To detect benzophenone 3 in rat whole blood after oral administration, HCl hydrolysis was required. Benzophenone-3 was found to produce a peak blood concentration 1 h after administration. Free benzophenone-3 in urine represented a very small percentage during the first 12 h after administration, while a higher concentration of the glucuronide conjugate was detected in the same time period. PMID- 1430777 TI - Mutagenicity studies on two triphenylmethane dyes, bromophenol blue and tetrabromophenol blue. AB - Bromophenol blue and tetrabromophenol blue are two triphenylmethane dyes. Triphenylmethane derivatives and their structurally related compounds, such as fluoresceins and xathenes, are widely used as industrial dyes for foods, drugs, cosmetics, textiles, printing inks or laboratory indicators. Since a number of these types of dyes have been reported to be genotoxic, safety concerns on these two dyes of interest have been raised. Consequently, a battery of genetic toxicology assays, including the Ames Salmonella/microsome assay, L5178Y TK+/- mouse lymphoma assay, mouse micronucleus test and mitotic recombination assay with yeast Saccharomyces cerevisiae strain D5, has been performed on each of the two dyes. The results of the evaluations indicate that both bromophenol blue and tetrabromophenol blue were not active and can be considered non-genotoxic for the three genetic endpoints assessed (gene mutation, chromosome aberrations and primary DNA damage). Genetic activities in some structurally related compounds of these dyes have been reported but may be attributed to the presence of mutagenic impurities rather than the compound itself. PMID- 1430778 TI - The influence of fenarimol on DNA synthesis and mitotic activity in rat liver. AB - Fenarimol administered in one single oral dose of 125 or 62.5 mg kg-1 body wt. day-1, respectively, stimulated rat liver enlargement at a dose-independent rate. Three single doses of fenarimol produced dose-dependent liver growth, whereas five single doses caused no further increase in liver weight. This increase was accompanied by an increase in hepatic DNA synthesis and mitotic activity, with a peak on the first day after the beginning of the experiments. The increase in binuclear hepatocytes and signs of necrosis suggested that the hepatomitogenic effect reflected a compensatory hyperplasia. After both three and five single doses the hepatomitogenic effect was suppressed, as a result of tolerance development. PMID- 1430779 TI - Relationship between eye and skin irritation in rabbits using a series of textile fiber finishes. AB - A series of 76 fiber finishes, typically composed of blends of lubricants, emulsifiers, antistatic agents and fatty acid soaps, were tested in rabbits to determine both the eye and the skin irritation potential. Each finish was classified as being either non-, slightly, mildly, moderately or severely irritating to the target tissue during a 48-h post-treatment period. Seven (9.2%) of the finishes tested were severely irritating to both the skin and the eye; two (2.6%) were determined to be non-irritating to both tissues. While occasionally finishes produced equal degrees of damage resulting in similar irritancy classifications, seven (9.2%) finishes were found to be severely irritating to the skin without producing any irritation in the eye. Conversely, one finish was found to be a severe eye irritant without producing any skin irritation. The suggested use of the skin irritation data to predict the ocular reaction needs to be carefully examined, particularly with materials such as these fiber finishes. The prediction that a severe skin irritant is also a severe eye irritant was demonstrated to be in error with 8 of 75 (10.5%) of the finishes studied. Further, there is little predictive association between the skin and eye irritation for these compounds. PMID- 1430780 TI - Effects of nickel hydroxycarbonate on alveolar macrophage functions. AB - The metabolic effects of different concentrations of nickel hydroxycarbonate (NiHC) on guinea pig alveolar macrophages (GPAMs) were investigated. Exposure to high concentrations of NiHC (6.25 and 12.5 micrograms 10(-6) cells) led to cell vacuolization. Morphological changes were associated with a dramatic reduction in the steady-state level of cellular adenosine triphosphate (ATP), i.e. ATP levels were reduced by 35% (P less than 0.001) and 53% (P less than 0.01), respectively. Low concentrations of NiHC (0.0625 and 0.125 microgram 10(-6) cells) did not induce morphological changes but increased cellular ATP content by 19% (P less than 0.01) and 12% (P less than 0.05), respectively. Effects of NiHC (0.125 and 6.25 micrograms 10(-6) cells) on cell oxidative metabolism were studied. The chemiluminescence was significantly increased (P less than 0.001) by the lower but not the higher concentration. A slight inhibition of total superoxide dismutase (P less than 0.05) and a decrease of catalase activity were demonstrated (P less than 0.05) for the high dose, while the low dose decreased the levels of reduced and total glutathione. In conclusion, the effects of NiHC on alveolar macrophages are characterized by an overproduction of free radicals for low concentrations and the depletion of cellular reserve energy, particularly ATP, for high concentrations. PMID- 1430781 TI - Preliminary report on the use of zinc in vivo to protect against nitrogen mustard toxicity in female Balb/cJ mice. AB - Previous studies with cultured normal human fibroblasts indicated that treatment of cells with zinc before exposure to an alkylating agent enhanced cell survival by seven- to ninefold. To establish whether a similar zinc-induced protective response could be elicited in vivo, we conducted a preliminary experiment in which Balb/cJ female mice were treated with zinc (2 mg kg-1 body weight) or saline by intraperitoneal (i.p.) injection at 48, 36, 24 and 12 h before i.p. administration of the alkylating agent nitrogen mustard (4 mg kg-1 body weight). Of the animals that received saline before nitrogen mustard, 57% died as compared with only 20% in the group treated with zinc before administration of the alkylating agent. As was observed in the studies of cells in culture, the results described in this report may suggest the existence in Balb/cJ female mice of a zinc-mediated protective response against nitrogen mustard toxicity. PMID- 1430782 TI - Attempted use of zinc in vivo to protect against nitrogen mustard toxicity in tumor-free and in L1210 leukemia-bearing female B6D2F1 mice. AB - The use of alkylating agents in treating cancer is limited by their toxicity to both normal and tumor tissue. Early in vitro studies indicated that zinc might be effective in mitigating this toxicity to normal tissue. The present studies were done to determine the capability of zinc to induce in vivo a protective response to an alkylating agent without also contributing to mortality. Tumor-free and L1210 leukemia-bearing female B6D2F1 mice were treated with zinc before administration of the alkylating agent nitrogen mustard. Protocols for administration route and frequency as well as the chemical formulation of the zinc were varied. The effect of a phytate-free diet was studied. Two parameters were used to determine the effectiveness of zinc in protecting animals from the toxicity of nitrogen mustard: the number of tumor-free mice that survived and an increase in the median life span of the tumor-bearing mice. The zinc-induction protocols used in these studies provided a limited degree of protection against nitrogen mustard toxicity in tumor-free female mice, but in tumor-bearing animals the protective response elicited with the protocols examined did not provide an appreciable therapeutic benefit. PMID- 1430783 TI - Phosphoric acid/phosphates. PMID- 1430784 TI - Erythrocyte and tissue AChE inhibition. PMID- 1430785 TI - Indoor air quality. PMID- 1430786 TI - A novel non-radioactive method for detection of nucleoside analog phosphorylation by 5'-nucleotidase. AB - Cytosolic 5'-nucleotidase has been implicated in the phosphorylation of certain nucleosides of therapeutic interest. In vitro, IMP and GMP serve as the optimal phosphate donors for this nucleoside phosphotransferase reaction. Existing assays for nucleoside phosphorylation effected by 5'-nucleotidase require a radiolabeled nucleoside as the phosphate acceptor and separation of the substrate-nucleoside from product-nucleotide has been accomplished either by a filter binding method or HPLC. However, detection of the phosphorylation of unlabeled nucleoside by HPLC is difficult since the ultraviolet absorbance of the phosphate donor, IMP, frequently obscures the absorbance of newly formed nucleotide. The use of ribavirin 5'-phosphate (RMP, 1,2,4-triazole-3-carboxamide riboside 5 monophosphate) as the phosphate donor obviates this difficulty since this triazole heterocycle does not significantly absorb at the wavelengths used to detect most nucleoside analogs. Using this procedure, a 5'-nucleotidase activity from the 100,000 x g supernatant fraction of human T-lymphoblasts deficient in adenosine kinase, hypoxanthine-guanine phosphoribosyltransferase, and deoxycytidine kinase, was characterized with regard to structure-activity relationships for certain inosine and guanosine analogs. PMID- 1430787 TI - A simple assay for determination of iron release from ferritin in neuroblastoma cells. AB - A commercially available enzyme immunoassay was used to determine ferritin content and subsequently the loading and release of iron from ferritin in neuroblastoma cells. LS cells were incubated with 59Fe for 24 h, lysed, and the cytoplasmic ferritin was bound to monoclonal antibodies coupled to globules. After determination of the ferritin content the same globules with bound radioactive ferritin were measured in a gamma-counter. To illustrate the applicability of this test system, increased iron loading of cellular ferritin could be demonstrated in cycloheximide-treated cells; furthermore, release of iron was documented after incubation of LS cells with a combination of 6 hydroxydopamine and ascorbate. The assay turned out to be a simple method for determination of changes in 59Fe content of ferritin in neuroblastoma cells. PMID- 1430788 TI - Assay of intracellular thymidylate synthetase activity and inhibition by 5-fluoro 2'-deoxyuridine in lymphocytes. AB - Thymidylate synthetase catalyses the formation of thymidine monophosphate from deoxyuridine monophosphate. Purified thymidylate synthetase can be assayed radiochemically using labelled deoxyuridine monophosphate as substrate, but cells are impervious to deoxyuridine monophosphate and so intracellular thymidylate synthetase activity cannot be assayed in this way. In this paper we describe the assay of intracellular thymidylate synthetase activity in intact cells using labelled 2'-deoxyuridine. The assay showed linear kinetics with respect to time, concentration of 2'-deoxyuridine, and cell concentration. 5-fluoro-2' deoxyuridine inhibited intracellular thymidylate synthetase activity measured with this assay by 50% at 5 nM. Cell growth was inhibited by 50% at 6 nM 5-fluoro 2'-deoxyuridine. The assay was specific for thymidylate synthetase and enabled measurement of thymidylate synthetase activity in situ in intact cells. PMID- 1430789 TI - Establishment of a multi-dose study of chondroitin sulfate iron colloid for evaluation of the reticuloendothelial system function. AB - The assay system of chondroitin sulfate iron colloid (CSFe) was established to evaluate the reticuloendothelial system (RES) function in individual rabbits. In the multi-dose study of CSFe, CSFe was repeatedly administered to each individual rabbit with increasing doses (0.6, 1.2, 2.4, 6.0 mg/kg) at set intervals. Blood samples were serially collected after injection of CSFe and the concentration of CSFe in serum was directly measured as an iron concentration by modifying the previously described assay method [1] to minimize the sample volume. The clearance rate of CSFe at each injected dose was computed by the least-squares method and the double-reciprocal plotting of the doses against the phagocytic velocities by the Lineweaver-Burk method was obtained in each rabbit. The maximum phagocytic velocity (Vmax) and the CSFe concentration producing 1/2 Vmax (Kp) obtained in ten rabbits were 0.129 +/- 0.025 mg/kg per min and 0.417 +/- 0.121 mg/kg (mean +/- S.D.), respectively. The results obtained from this multi-dose study were comparable to our previous results obtained from the mean values of five groups given different doses [1]. The clearance rates of CSFe (0.6, 1.2, 6 mg/kg) decreased after the co-injection of 80 mg/kg of carbon colloid. The calculated Vmax and Kp in 29 rabbits were 0.125 mg/kg per min and 1.167 mg/kg. The Kp was apparently greater than that of the control (Vmax = 0.128 mg/kg per min, Kp = 0.421 mg/kg). Carbon colloid (80 mg/kg) was injected to six rabbits after the completion of the first multi-dose study of CSFe and then the second multi-dose study of CSFe was repeated after 24 h. No differences were found in Vmax and Kp between the two studies as were in the control group (10 rabbits) where saline was injected instead of carbon colloid. These results indicated that carbon colloid (80 mg/kg) gives a competitive and reversible inhibition on the RES. This multi-dose study of CSFe may be applicable for a bed-side analysis of the RES function in a patient. PMID- 1430790 TI - Development of an antibody against a 170-kDa fragment of fibroin isolated from cocoon fibres of Bombyx mori. AB - A simple method for the isolation of denatured fragments of the fibroin protein from cocoon fibres by alkali solubilization is discussed. This 170-kDa antigen has been purified and used to raise the polyclonal antibody in rabbit. The specificity of this antibody to the purified cocoon protein has suggested strong immunoreactivity up to a titre of 1:5000 dilution of the antibody. Further, dot blot analysis with the tissue extracts from silk glands of different larval stages (3rd to 5th) reveals that this antibody reacts showing a stage-specific increase in the intensity of the colour, correlating well with the in-vivo expression of the silk protein. This study suggests the availability of a specific polyclonal antibody that detects the native fibroin with no crossreactivity with other tissue proteins. PMID- 1430791 TI - A new micromethod for mechano-chemical research. AB - A new micromethod to study activity of enzymes in crystalline and amorphous solid samples subjected to tension is described. Both static (up to 200%) and dynamic (with an amplitude up to 50% and frequency of 10(-3)-50 Hz) deformation may be applied to the sample during the activity measurement. Strain-induced changes in activity of thin (3-10 microns) needle-like strips (0.2-0.5 microns long), cut out of the microtome sections of cross-linked crystals of pancreatic carboxypeptidase A is measured in a droplet of substrate solution (with volume of 10(-6)-10(-9) l) with a pH-microelectrode technique. PMID- 1430792 TI - Characterization of immobiline membranes for application in a multicompartment electrolyzer for protein purification. AB - The efficient use of preparative protein purification in a multicompartment electrolyzer with Immobiline membranes depends on the knowledge of membrane characteristics. For that purpose, an experimental investigation of the effects of ionic charges on the membrane characteristics has been carried out through the measurements of membrane swelling and conductance. We also investigated the effects on the electrolyzer behaviour of operating parameters such as the Immobiline concentration and the presence of ion-exchange membranes. Data show that polyacrylamide gel degree of swelling is strongly dependent upon the pH and the ionic strength of the bathing solution as well as on the type and molarity of charges incorporated in the gel. The conductance of supported Immobiline gels in contact with uni-univalent chloride solutions has been measured by means of a mercury cell. The membrane conductance is also influenced by the ionic strength of the equilibrium solution and the presence of weak ionizable groups in the gel matrix. This study has demonstrated the close link between electrochemical and electromechanical properties of Immobiline membranes. PMID- 1430793 TI - Decreased Coomassie brilliant blue colour yield with glycated proteins. AB - Collagen, myosin and albumin were incubated for 7 days at 20 degrees C with fructose, ribose or glyceraldehyde. For thus-formed glycated proteins, quantities were determined by the Conway microdiffusion technique and by the colorimetric method based on Coomassie brilliant blue G-250 colour yield. It was found that when albumin was glycated with increasing amounts of glyceraldehyde, the colour yield was decreased by 7-33%. In collagen, myosin and albumin incubated with 0.5 mol/l fructose, 0.5 mol/l ribose or 0.1 mol/l glyceraldehyde, protein concentration was not changed, as proved by the Conway microdiffusion technique; the Coomassie brilliant blue G-250 colour yield was up to 50% lower, depending on the protein used, and was decreased much less when proteins were incubated with less sugar. PMID- 1430794 TI - Effect of chemical sympathectomy on scintigraphic gastric and small bowel transit in the rat. AB - Our aims were to measure gastric and small bowel transit of radiolabeled chow or liquids in rats and to assess the effect of pharmacologically induced chronic sympathectomy of at least 5 weeks duration. Three series of experiments were performed. In series I, four rats in each group underwent i.p. chloral hydrate anesthesia, tracheostomy with intubation and mechanical ventilation: they received by gavage 1.0 g rat chow dissolved in 1.5 ml saline labeled with 1.0 mCi 99mTc-DTPA In series II, four rats in each group were anesthetized with only i.p. chloral hydrate and received 1.5 ml labeled saline. Rats were placed on a gamma camera for dynamic acquisition of 1-min images for 7 h in series I, and 4 h in series II. Activity was quantitated in stomach and cecum; gastric emptying was analyzed by the power exponential model. In series III, four rats in each group were studied for 1 h on gamma camera and sacrificed after 5 h. At the end of each study, the stomach, small bowel, cecum and colon were removed and radioactivity counted in each organ in a dose calibrator. Quantitation of radioactivity by gamma camera was highly accurate: labeled chow in the stomach at 7 h was identical by external camera and counting of the excised organ (linear regression slope = 1.01, r = 0.97, P less than 0.0001). Similar precision was observed with labeled liquids (slope = 0.93, r = 0.93, P = 0.001). Chow emptied slower than liquid in both groups (P = 0.048). Ileocecal movement of isotope occurred by bolus transfers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430795 TI - Structure of autonomic neuromuscular junctions in the sinus venosus of the toad. AB - The structure of cholinergic and adrenergic neuromuscular junctions in the sinus venosus of the toad, Bufo marinus, was determined by electron microscopy. From random sections of sinus venosus tissue it appeared that there were variable separations between cholinergic or adrenergic varicosities and the nearest sinus venosus muscle cell. However, when the structure of complete cholinergic and adrenergic varicosities was determined by examining serial electron micrographs, virtually all varicosities that lost their covering of Schwann cell were found to form an area of close apposition with an adjacent muscle cell. At the region of close apposition, the neuromuscular cleft was filled with a single layer of basal lamina to give a neuromuscular separation of about 70 nm. Synaptic vesicles within a varicosity were usually found to be concentrated towards the region of close apposition. These observations are discussed in relationship to the idea that when transmission occurs at these neuromuscular junctions the transmitters act on discrete pools of specialized subsynaptic receptors. PMID- 1430796 TI - Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activity in humans. AB - To clarify the effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a precursor of norepinephrine (NE), the effect of this drug on microneurographically recorded muscle sympathetic nerve activity (MSA) from the tibial nerve was analyzed in ten healthy male volunteers. A single dose of 600 mg of L-threo-DOPS was orally administered and the effect of this norepinephrine precursor on MSA at resting and at upright standing positions, as well as the MSA responsiveness to head-up tilting was examined by comparing the data obtained after administration of the drug with those obtained under control conditions. The plasma NE levels were determined in two subjects. The results were as follows: (1) resting MSA increased significantly 80 min after administration of L threo-DOPS and was accompanied by an increase in plasma NE levels; (2) standing MSA when treated with the drug was not significantly different from values obtained under control conditions; and (3) MSA responsiveness to orthostasis was reduced after L-threo-DOPS. We conclude from the activation of MSA by L-threo DOPS that this drug raised blood pressure not only through an increase in metabolized plasma NE levels, but also through the enhancement of MSA by activation of descending noradrenergic or adrenergic pathways proximal to the recording site of the sympathetic discharge. PMID- 1430797 TI - Differential effects of V2 vasopressin agonist and antagonists on blood pressure regulation in normotensive (WKY) and spontaneously hypertensive (SHR) rats. AB - The effects of arginine vasopressin analogs with V2 agonistic and antagonistic properties on blood pressure (BP) and heart rate (HR) were compared in conscious, spontaneously hypertensive (SHR) and normotensive (WKY) rats under resting conditions and after administration of phenylephrine (Phe) and sodium nitroprusside (SN). In WKY rats, resting BP and HR were not significantly affected during intravenous (i.v.) infusion of dVDAVP, (V2 agonist; 200 pg/kg/min), d(CH2)5 (D-Ile2,Abu4]AVP (V2 antagonist 1; weak V1 antagonist; V2/V1 ratio = 29; 0.6 microgram/kg/min), d(CH2)5[D-Ile2,Ile4,AlaNH2]AVP (V2 antagonist 2; very weak V1 antagonist; V2/V1 ratio = 83; 0.6 microgram/kg/min) and combined infusion of V2 agonist and V2 antagonist 2. Under resting conditions BP and HR were not affected in WKY by any of the treatments. In SHR rats BP and HR were significantly decreased by V2 antagonist 2 infused alone or in combination with V2 agonist. In WKY but not in SHR V2 agonist without and with prior V2 receptors blockade significantly augmented bradycardia associated with a maximum increase of the systolic blood pressure after Phe administration. Significant differences were found between SHR and WKY in SN-induced changes of HR and BP after administration of V2 agonist and antagonists. The results suggest that circulating vasopressin may modify the baroreflex by interaction with receptors which are stimulated by V2 agonist but are different from the classical V2 receptors. The study supports evidence for differential effects of vasopressin analogs on blood pressure and blood pressure-heart rate relations in WKY and SHR. PMID- 1430798 TI - [Use of perfluorocarbon solutions in the surgical treatment of posterior luxation of the lens]. AB - Posterior lens dislocations represent 20 to 40% of all lens dislocations. It can occur after trauma. Visual prognosis can be good, but most often there are complications such as glaucoma, retinal detachment and uveitis. A few years ago, surgery was difficult, and surgery was delayed until the development of specific complications. A new technique, using perfluorocarbon liquids (PFCL), should be recommended because it is simple, and constantly effective. After vitrectomy, perfluorodecalin is injected into the vitreous cavity. As PFCL have a density twice the density of water, it allows the lens to float on the surface of the PFCL, behind the iris. Lens extraction can be associated with trabeculectomy, and anterior chamber lens implantation. We present a prospective study of 6 cases operated according to this technique. Postoperative results were good: visual acuity was preserved and ocular tension was controlled in cases of preoperative hypertonia. We believe this technique can be recommended after posterior lens dislocation, to prevent complications and to preserve visual acuity. PMID- 1430799 TI - [Surgical treatment of strabismus by sagittal cutting of the oblique muscles. Apropos of 449 cases]. AB - The theoretical proposals and the therapeutic approach described at the beginning of the sixties by Gobin concerning the treatment of incomitant strabismus have had such positive results as to convince many surgeons to adopt this methodology. The principal merit of Gobin's technique lies in evaluation of all aspects of the strabismus (horizontal, vertical and oblique) searching for the obstacles to ocular movements which cause alteration of binocular vision and removing them. According to the above criteria, we have operated 449 cases of incomitant strabismus due to sagittalization of the oblique muscles. The validity of this technique has been demonstrated by the results obtained in a single operation (a success rate of over 50%). With a second operation the success rate was increased to 70% (orthophoria, heterophoria and esthetic angle < 7 degrees). PMID- 1430800 TI - [Changes in the fundus in subacute sclerosing panencephalitis. Apropos of 23 cases]. AB - Subacute sclerosing panencephalitis (SSPE) is a fatal slow encephalitis. It is related to a chronic infection of the central nervous system by a defective measles virus. Among 41 patients with SSPE, 23 had ocular involvement. The ophthalmologic involvement preceded the onset of neurological signs in 4 cases, they were detected at first presentation in 9 cases, and they occurred in the course of the disease in 10 cases. The ocular involvement was bilateral in 19 cases. Various ophthalmologic features were reported: retinitis (16 eyes), macular pigment disturbances (4 eyes), optical neuritis (33 eyes), visual agnosia (1 patient). The macular lesions were typical of the disease, but at the acute stage they were liable to be confused with toxoplasmosis. This complication of measles should disappear with the systematic vaccination of 12 month old children. PMID- 1430801 TI - [Intraocular absorption of cyclosporin A eyedrops]. AB - A study was carried out on ocular and systemic absorption after topical application of 2% cyclosporin A in patients requiring corneal transplants, determining by polarized light immunofluorescence the levels of this drug in the cornea, aqueous humor and blood. Between 30 and 85 minutes after the last application, considerable levels of cyclosporin A were found in the explanted cornea (236 +/- 42 ng/mL). Relatively lower levels were found in the aqueous humor although there were significant differences between the patients who received a total topical dosage of 5 mg (16.92 +/- 6.86 ng/mL) and those who received 10 mg (25.06 +/- 9.13 ng/mL) over the same period of time. No analytically detectable levels were found in the plasma. We consider that topically administered cyclosporin A can reach immunosuppressive levels of activity in some ocular compartments thus eliminating the potential systemic effects resulting from its utilization by general administration. PMID- 1430802 TI - [Persistent hyperplastic primary vitreous. Middle-term results of vitrectomy]. AB - In this study, the authors present a homogeneous series of seven children suffering from persistent hyperplastic primary vitreous, in its complete anterior and posterior form. These children were operated by pars plana lensectomy and vitrectomy. The surgical operation was beneficial in every case: not only were there no complications, but the operation also prevented progression towards neovascular glaucoma, vitreous hemorrhages and phtisis bulbi. In addition, one of the benefits of this technique was esthetic, with the disappearance of leucocoria, the occasional correction of strabismus and the reduction in microphthalmos. Visual recovery can be surprisingly good, in the absence of any associated retinal malformation. PMID- 1430803 TI - [Orbito-palpebral prosthesis retained by intraosseous implants]. AB - The use of intraosseous implants, whose tolerance is continually improving, constitutes an important progress in the field of prosthetic rehabilitation. In particular, titanium implants largely resolve the problem of retention of craniofacial prostheses. Our experience, based on that of Swedish authors concerning the extra-oral use of intraosseous implants, was sufficiently convincing to adopt this effective technique in our patients candidates for prosthetic rehabilitation. The case of a patient rehabilitated by means of an orbito-palpebral prosthesis is presented after a brief biomechanical review and presentation of the technique. Our results, although preliminary, are very encouraging in terms of the technical aspects as well as patient comfort. A further study could reinforce our decision. PMID- 1430804 TI - [Giant peripheral tear of the retinal pigmented epithelium]. AB - The authors present a case of gigantic tear of the retinal pigmented epithelium. This tear was situated in the middle periphery and seems to have appeared spontaneously together with a carotid-cavernous fistula. The functional outcome was favorable. The authors deal with the various possible patho-physiological mechanisms. PMID- 1430805 TI - [Serpiginous choroiditis]. PMID- 1430806 TI - [Eye controlled microscope used in ophthalmic microsurgery]. AB - This article presents a system of oculomotor control of the microscope used in ophthalmic microsurgery. An eye movement sensor has been integrated within the microscope lens. The information provided by this sensor is used to control the position of the microscope with no alteration of the surgeon's visual functions and no interference with his visual sensori-motor reflexes. Results have been obtained from laboratory experimentations as well as from a series of anterior and posterior segment surgical procedures. They demonstrate the high precision and sensitivity of the gaze control which can be used to compensate for the reduction of the field of vision resulting from the optical magnification of the microscope. PMID- 1430807 TI - [Questions to consultants. Anisometropia following surgery, apropos of a case]. PMID- 1430808 TI - [Granuloma of the conjunctiva caused by synthetic fibers]. AB - A five year old girl with pseudo-tumoral lesion of the inferior right fornix underwent surgical excision. Histology of the lesion showed a granulomatous giant cell inflammation surrounding foreign material, probably related to synthetic fabric fibers. PMID- 1430810 TI - [Monobloc PMMA lenses. Anteroposterior displacement of the implant as a function of the insertion diameter]. AB - Data concerning the biomechanical properties of IOL are rare. A systematic study of these properties was performed in the "laboratoire de Mecanique des Structures" at the "Ecole Centrale de Nantes". The results of the anteroposterior displacement of the optical part of eleven posterior chamber lenses (all PMMA) which were subjected to a diameter reduction, are reported. The deplacement of the implants was very slight and the position of the posterior side was relatively anterior whatever the diameter of insertion. The clinical implications, especially concerning the posterior capsule, are discussed. PMID- 1430809 TI - [Is A29, B12 vasculitis caused by the Q fever agent? (Coxiella burnetii)]. AB - The authors describe the first two cases, to their knowledge, of retinal vasculitis, associated with Q fever. The first case was a chronic infection induced by Coxiella burnetii associated with HLA group A29 and B12; in the second case, the phenotype was B12. The authors tried to determine whether this agent could be the "Birdshot chorioretinopathy" promoting factor. Several epidemiologic findings tend to prove that Q fever is not the only cause. On the other hand, its similarity with rickettsia, the fact that it is found in patients with vasculitis, suggest that it could be one of the initial causal factors. PMID- 1430811 TI - [Long-term results of successful surgical treatment of retinal detachment by vitrectomy and silicone oil injection. Effect of removal of the tamponade on further complications]. AB - We present, with a minimal follow up of six months, the results of 118 silicone oil removals following successful treatment of retinal detachment by pars plana vitrectomy and silicone oil injection. A recurrent retinal detachment occurred in 8.5% of cases, 13% of the 61 phakic eyes at the time of silicone oil removal maintained a clear lens, 29.6% of the eyes had a raised intraocular pressure and 6.8% had a keratopathy. The visual acuity improved in 72.8% of eyes after silicone oil removal. The main reasons for a late decrease in visual acuity were recurrence of the detachment, hypertonia, chronic hypotonia and keratopathy. All the eyes with late complications after silicone oil removal had a clinically significant droplet dispersion in the anterior chamber. Only complete and early silicone oil removal seems to decrease the complication rate. PMID- 1430812 TI - [Posterior luxation of lens or implant: surgical treatment using a perfluorocarbon solution. Technique and results of 13 cases]. AB - We used perfluorocarbon liquids in the management of 6 cases of posterior dislocation of the lens and 7 cases of (sub-) luxation of a posterior chamber intraocular lens (IOL). The perfluorocarbon liquid was injected into the vitreous cavity after complete vitrectomy, to bring back the lens or IOL to the posterior chamber where it can be easily removed. The main characteristics of perfluorocarbon liquids used in this indication are their high specific gravity and their good surface tension. Because of these two qualities, when injected in a vitrectomized eye, the perfluorocarbon liquid forms a bubble, filling the vitreous cavity from the posterior pole to the ora serrata with the dislocated lens or IOL floating on its surface. We found this technique to be helpful and quite atraumatic in this difficult surgical situation. Complications included regressive corneal edema in 6 cases and retinal dialysis with localized detachment in 3 cases. PMID- 1430813 TI - [Ocular prognosis in Behcet's disease]. AB - The ocular prognosis of Behcet's disease was assessed in 31 French native patients with ocular involvement. The mean follow-up time was 6 years. Ophthalmologic manifestations revealed the disease in 61% of patients, and it was the first symptom in 29%. Two groups of patients could be identified: the minor forms (23%) which remained stable with colchicine alone and the severe forms (77%) which required steroid (32%) and/or immunosuppressive (45%) therapy. In the severe forms, 32 eyes were unchanged, 4 eyes showed improvement, and 12 eyes showed deterioration in visual acuity. Positivity of HLA B5, sex and complete form of the disease were not predictive factors of ocular involvement, or of its seriousness. At 6 years, 16% of the eyes (versus 14% at the beginning) had a visual acuity less than 1/10, and 71% (versus 74% at the beginning) had a visual acuity greater than 8/10. A close collaboration between ophthalmologists and internists allows a good visual prognosis in Behcet's disease. PMID- 1430814 TI - [Cicatricial ectropion and ichthyosis. Apropos of 4 cases]. AB - Ichthyosis are dystrophic inheritance skin disorders with inconstant palpebral complications like cicatricial ectropion and lagophthalmos due to large skin retractions. The authors report two cases of cicatricial ectropion in two adults. For one of the two cases, it is the first description to our knowledge of cicatricial ectropion associated with ichthyosis vulgaris sex-linked. The authors, after a short description of physiopathology and of classification of the different types of ichthyosis describe the surgical treatment with skin grafts, with good results in the first post operative period only in two adults. The two newborns had good results with medical treatment only. PMID- 1430815 TI - [Large orbito-palpebral cavernous hemangioma]. AB - Cavernous hemangiomas are benign vascular orbital lesions that exert a slowly progressive mass effect. They usually occur in adults. The authors report an unusual case of a large orbito-palpebral cavernous hemangioma with peculiar history and symptoms. The main clinical and radiological characteristics of this tumor are recalled together with the basis of surgical management. PMID- 1430816 TI - [Corneal cyst]. AB - A 76-year old woman developed an intracorneal cyst following uncomplicated cataract surgery. Progressive enlargement led to partial visual loss. Following drainage of the cyst, cytopathologic examination showed epithelial cells. The cyst subsequently reformed and caused acute pupillary block. Repeat drainage and cryotherapy were performed. Vision was limited by corneal edema, and penetrating keratoplasty was performed. PMID- 1430817 TI - [Fluid-air exchange]. PMID- 1430818 TI - [Questions to consultants. Treatment of adenovirus keratoconjunctivitis apropos of a case]. PMID- 1430819 TI - Surgical lengthening of the Achilles tendon. PMID- 1430820 TI - Enlargement of the entire posterior aspect of the calcaneus: treatment with the Keck and Kelly calcaneal osteotomy. AB - Painful enlargement of the entire posterior aspect of the calcaneus can be difficult to effectively treat and must be differentiated from a classical Haglund's deformity. Clinical, radiographic, and surgical treatments of this deformity will be discussed. An illustrative case presentation is also included. PMID- 1430821 TI - First cuneiform closing abductory osteotomy for reduction of metatarsus primus adductus. AB - The closing subtraction osteotomy of the first cuneiform effectively reduces pronounced obliquity of the first metatarsal cuneiform joint and predictably reduces the intermetatarsal angle in patients with metatarsus primus adductus. This osteotomy is combined with other procedures in surgical realignment of the first ray. Cases best suited for this procedure must be selected carefully. The procedure involves resecting the existing bone block from the opposing surfaces of the first and second metatarsal bases and from the distal one half of the opposing surfaces of the first and second cuneiforms. A triangular-shaped wedge of bone is then resected from the midbody of the first cuneiform while retaining a medial hinge. Closure of the first cuneiform osteotomy should require only minimal pressure. Two threaded Steinman pins transfix the osteotomy site. The vascular cancellous bone of the first cuneiform assures adequate healing of the osteotomy site. PMID- 1430822 TI - A new method of repair for rupture of the Achilles tendon. AB - Rupture of the Achilles tendon requires prompt and appropriate treatment to prevent prolonged or permanent disability. Although the literature abounds with evidence supporting both conservative and surgical treatment, more recent studies report lower rerupture and complication rates with surgical repair. The development of ligament anchoring devices has led to new methods of repair for ligament and tendon injuries. A modification of the Lindholm technique that utilizes these devices is presented. PMID- 1430823 TI - A calcaneal fracture from a fall or a fall from a calcaneal fracture? AB - A case of a calcaneal avulsion fracture from a relatively minor traumatic incident is presented. The mechanism of calcaneal avulsion fractures is discussed. Special attention is given to the possibility of a pathologic fracture. The literature is reviewed and treatment is discussed. PMID- 1430824 TI - Forces on the first metatarsophalangeal joint: a pilot study. AB - The following is a pilot study designed to examine the forces in and around the first metatarsophalangeal joint during the contact phase of the normal gait cycle. The architecture of this study was designed to be simple, effective, and repeatable with minimal complications. This study used a force plate to examine ground reaction forces with the simultaneous use of a video tape recorder to provide overlapping images of the angular displacement of the proximal phalanx on the first metatarsophalangeal joint coinciding with these ground reaction forces. Peak ground reaction force was found to be 1.16 x body weight while the proximal phalanx was found to be maximally dorsiflexed just 0.09 seconds after the peak ground reaction force. The mean range of motion during this process was found to be 31.54 degrees. PMID- 1430825 TI - A modification of the Ellis Jones procedure for chronic peroneal subluxation. AB - The authors present a modification of the classic Ellis Jones procedure. The modification primarily involves the technique used for tenodesis of the transferred slip of Achilles tendon to the fibula. Advantages and disadvantages are discussed, as well as the results of 31 cases. PMID- 1430826 TI - Septic shock syndrome in the surgical wound care patient. AB - The occurrence of septic shock in lower extremity surgery is rare. Its early identification and treatment are vital to its outcome. The authors present a case history of septic shock occurring in the surgical wound care patient, discuss the pathophysiology of septic shock, and then consider diagnosis along with treatment options. PMID- 1430827 TI - Invasive melanoma of the hallux. AB - The authors present a classic case of superficial spreading melanoma. Superficial spreading melanoma is the most commonly acquired cutaneous malignant melanoma. Its true etiology is unknown. Superficial spreading melanoma may remain in the epidermis with peripheral extension (radial growth phase) for as long as 5 years before invading deeper tissue layers. Definitive diagnosis is established through biopsy. Treatment, following biopsy, involves wide radical excision, and possibly lymphadenectomy and combination chemotherapy depending on the extent of the pathology. PMID- 1430829 TI - Biofix absorbable system. PMID- 1430828 TI - Austin bunionectomy: postoperative MRI evaluation for avascular necrosis. AB - The authors used magnetic resonance imaging (MRI) to evaluate the formation rate of avascular necrosis following performance of 20 modified Austin bunionectomies. Five modified McBride bunionectomies without first metatarsal osteotomy were also performed as an MRI control. Results showed an avascular necrosis formation rate of 50%. The majority of the avascular necrosis areas were found dorsally within the cancellous bone substance of the first metatarsal head. These lesions, in all cases, did not cause any patient disability or result in any decline in the degree of patient satisfaction. The MRI positive avascular necrosis evaluations do suggest potential problem areas with the surgical technique that may be eliminated through further modification of the classic Austin bunionectomy procedure. PMID- 1430830 TI - Fifth metatarsal distal oblique wedge osteotomy utilizing cortical screw fixation. AB - A retrospective study of 26 tailor bunionectomies is presented. The use of an apical axis guide, reciprocal planing, and strict application of Association for Osteosynthesis principles offers ease of application, increased stability, and greater healing predictability than other techniques. Potential complications such as angular displacement, shortening, nonunion, and transfer lesions are minimized. PMID- 1430831 TI - The cytological and biochemical implications of periungual fibroma. AB - Periungual fibromas may be acquired lesions or they may be associated with tuberous sclerosis or von Recklinghausen's Disease. Such tumors are comparatively rare benign dermatological entities. Periungual fibromas associated with the posterior nail fold have a potential for inducing deforming nail deformity. Pain resulting from the growth is due to concentration of pressures which may be placed on the nail matrix and contiguous soft tissue structures. This is further complicated by compression developed within the toe box of the shoe. The preferred treatment in symptomatic cases is that of complete surgical excision of the entire lesion. The present study presents such a case, together with histopathological features of this type of growth, with special emphasis on the subcellular features of the neoplasm. PMID- 1430832 TI - A modification of the Regnauld procedure for hallux limitus. AB - Surgical correction of hallux limitus can be challenging to the foot surgeon. The procedures available to date are numerous. Satisfactory results require proper candidate selection, and other procedures must be weighted carefully. The Regnauld procedure has become an accepted technique in this extensive surgical armamentarium. This manuscript describes a means of fixation that eliminates many of the complications associated with the original nonfixed technique, and allows for early range of motion to be initiated. PMID- 1430833 TI - Chronic ankle instability and pain: a case report of a teenager with open epiphysis. AB - The author discusses the treatment of chronic ankle instability in a young child of 14 years of age. A procedure is described that avoids drilling of the fibula and disruption of the epiphyseal plate. An autogenous graft procedure is described. PMID- 1430834 TI - Acquired fibrokeratoma of the heel. AB - Acquired fibrokeratomas traditionally have been classified by both appearance and anatomical location. They are benign, solitary lesions that characteristically involve the digits of the hands and feet. The authors present a case with unusual involvement of the plantar surface of the heel. PMID- 1430836 TI - Classics in conventional radiography of the foot. AB - The authors display a variety of conditions that can be recognized using standard pedal radiographs. Letter markings on the enclosed x-rays denote the particular areas of interest. Brief descriptions of the pathologic conditions are also provided. PMID- 1430835 TI - Rigid internal fixation of the Austin/Chevron osteotomy with Herbert screw fixation: a retrospective study. AB - One of the adaptations of the Herbert bone screw (Zimmer Corp., Warsaw, Indiana) in podiatric surgery has been in the fixation of the Austin type osteotomy of the first metatarsal, to obtain rigid internal fixation. Technical difficulties in performing the procedure and complications have resulted in the development of several modifications of the original technique to better facilitate application of the Herbert screw. A brief review of the literature including history of distal metaphyseal osteotomies, and the uses of the Herbert screw is included. The purpose of this manuscript is to present utilization of the Herbert bone screw and modified jig in a modified Austin osteotomy, and to produce rigid internal fixation without the disadvantages of other internal fixation techniques. PMID- 1430837 TI - Phalangeal periosteal (juxtacortical)chondroma of the foot. AB - The author discusses a benign cartilaginous tumor involving the tubular bones, more frequently in the hand than the foot. Its rare occurrence in the second toe of an adult male is illustrated. Pain and swelling required excisional biopsy, whose diagnosis was aided by radiographic findings of calcification and cortical erosion. PMID- 1430838 TI - Modulation of pituitary gonadotropins and prolactin secretion by testosterone in vitro. AB - Investigations were undertaken to study the differential modulation of LH, FSH and PRL secretion by testosterone (T) using whole pituitary (PI) or pituitary hypothalamus coincubates (PHC) as in vitro constructs. PI and PHC from intact and castrated rats were incubated with or without T thrice, for 24 h each, (24 h x 3, total incubation period 72 h). The spent media was replenished every 24 h. At the end of 72 h, a few of the pituitary glands were challenged with 10 nM LHRH for 4 h. The spent media and pituitary glands were analyzed for LH, FSH and PRL using specific RIAs. Incubation of PI or PHC from intact rats with T stimulated the release of LH and FSH but inhibited the release of PRL. T had no effect on the intrapituitary contents of LH but inhibited intrapituitary contents of FSH and PRL, as compared to controls incubated without T. Castration increased intrapituitary contents of LH and FSH with concomitant decrease in PRL levels. Incubation of PI or PHC from castrated rats with T inhibited intrapituitary contents of LH to intact pituitary levels, while PRL levels were further reduced instead of being ameliorated. It is concluded that PI or PHC can be used as convenient in vitro models to monitor the effect of castration or of T modulation of pituitary and hypothalamus functions. T does not affect the synthesis of LH at the gonadotroph level but facilitates the regulation of intracellular LH and FSH levels. It is postulated that T inhibits the synthesis of FSH/PRL at the gonadotroph/lactotroph levels. PMID- 1430840 TI - Use of granulosa-luteal cell culture to evaluate low and high clinical responses to menotropin stimulation. AB - The cause of a poor response to human menopausal gonadotropin (hMG) remains unexplained. To determine whether aromatase activity of cultured granulosa cells obtained from relatively low estradiol (E2) responders (serum E2 < 1000 pg/ml) to hMG therapy differed from that of good responders (E2 > or = 1000 pg/ml), we prospectively compared serum E2 on the day of human chorionic gonadotropin administration to in vitro aromatase activity following a 72-h culture. Granulosa cells were obtained from seven women undergoing hMG therapy and oocyte aspiration. Follicle stimulating hormone (FSH) was added to one-half of the cultures. Serum E2 was determined by radioimmunoassay, and aromatase activity was determined indirectly by measuring tritiated water formed by aromatization of 1 beta [3H] androstenedione to estrogen in 1 h. In this study, luteinized granulosa cells from patients with a relatively low serum E2 produced less estrogen in cultures when compared to cells from higher responders (p < 0.01). Aromatase activity was not significantly increased by FSH in the relatively high responders, whereas FSH stimulated a significant increase in aromatase activity in cells from lower responders (p < 0.001). Our results indicate that the clinical response to hMG is at least partly due to the "quality" of granulosa cell aromatase activity. A clinically relevant "block" to FSH action may be present in vivo in low responders which can be reversed in culture by addition of FSH. PMID- 1430839 TI - Pituitary reserve after repeated administrations of releasing hormones in young and in elderly men: reproducibility on different days. AB - Combined testing of the pituitary gland by administration of GHRH, CRH, GnRH and TRH has been proposed for clinical studies, although some reports indicate that individual endocrine responses can be different when releasing hormones are used alone or in combination. Aims of this study were to evaluate: 1) the reproducibility of the combined test on different days; 2) the endocrine responses to the combined test applied twice at 3h and at 5h interval; 3) differences of endocrine responses in young and in elderly men. Six healthy young men (aged 25 to 35 yr) and 6 healthy elderly men (aged 65 to 75 yr) were evaluated: elderly men had lower testosterone, free T3, and somatomedin-c levels than young men, while 17 beta-estradiol and inhibin were not significantly different, all values being within normal laboratory limits. The 12 men were tested on day 1 with iv GHRH (50 micrograms) CRH (50 micrograms), GnRH (100 micrograms) and TRH (200 micrograms) at 08:00h and again at 11:00h; on day 8, the same men were tested at 08:00h and again at 13:00h. At 08:00h, the endocrine responses were similar on day 1 and on day 8. The second GH (young and elderly men) and PRL (only young men) response was blunted on day 1, when the interval between two consecutive stimuli was 3h, but not on day 8, when the interval was 5h. Elderly men differed from young men only for GH and for PRL release on day 1 at 08:00h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430841 TI - Changes in lymphoid organs of Ames dwarf mice after treatment with growth hormone, prolactin or ectopic pituitary transplants. AB - This study was performed to obtain more insight into the roles of PRL and GH in the control of immune functions in hereditary dwarf mice characterized by severe immunodeficiency. Adult female Ames dwarf mice (df/df) were injected daily for 10 days with ovine PRL (oPRL), bovine GH (bGH), oPRL+bGH or were implanted with a normal pituitary under the kidney capsule for 5 days. Only the treatment with bGH resulted in significant increases in the gain of body weight, and in absolute and relative thymus and spleen weights. Treatment with oPRL alone did not affect body weight gain or thymus and spleen weights. Treatment with oPRL+bGH produced a significant increase in the gain of body weight and in absolute and relative spleen weight but these effects were smaller than those measured in dwarf mice treated with bGH alone. Only bGH therapy resulted in extensive recovery of the absolute number of lymphocytes in the thymus and spleen of dwarf mice, with the values in treated dwarf mice not significantly different from those found in normal non-dwarf females. However, when these values were corrected for body weight, both the splenic and the thymic indices exceeded the values found in normal mice. The absolute numbers of lymphocytes in the spleen were also increased by oPRL+bGH treatment, but did not reach the values found in normal mice; however, the splenic index exceeded the values found in normal animals. Surprisingly, the absolute and relative numbers of lymphocytes found in the thymus of dwarf mice under oPRL+bGH therapy were indistinguishable from those found in oPRL or vehicle treated dwarf mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430843 TI - Diencephalic idiopathic gliosis: an unusual hypothalamic syndrome of dermopathy, diarrhea and growth arrest. AB - This case report of a 16-year-old girl describes the association of chronic diarrhea and lower limb dermopathy with an unusual and widespread gliosis within hypothalamic and other diencephalic structures. This syndrome to our knowledge has not been previously reported. Hypothalamic disease was suggested during life by examination findings of sustained hypothermia, altered sleep-wake cycles and abnormal cortisol diurnal rhythms. Profound growth arrest from the age of 8 yr (growth velocity < 1.4cm/yr) despite normal levels of growth hormone and response to physiological stimuli were additional unusual features. Autopsy after sudden death at 16 yr showed extensive gliosis in hypothalamic and adjacent diencephalic structures with proportionately little neuronal loss--suggesting an unidentified stimulus to glial proliferation. In the absence of evidence of other organ dysfunction it is suggested that dermopathy and chronic diarrhea in this case may have an autonomic basis. The impaired tissue response to growth hormone could be due to chronic hypothermia or involvement of some other (unidentified) hypothalamic factor regulating growth velocity. PMID- 1430842 TI - Alterations in the concentrations and binding properties of sex steroid binding protein and corticosteroid-binding globulin in HIV+patients. AB - The abnormal concentrations of steroid hormones and free fatty acids in the plasma of HIV-infected subjects are associated with qualitative and quantitative alterations in two of the major steroid hormones carrier proteins, sex steroid binding protein (SBP) and corticosteroid-binding globulin (CBG). The properties of SBP and CBG in the sera of two age-matched groups of 67 men healthy blood donors (controls) and 64 HIV+subjects: 11 CDC group II and III (ASY), 6 CDC group IVA and 47 groups IV C1+D (AIDS) were analyzed. The HIV+patients had SBP concentrations 39-51% above those of controls. The sera of AIDS patients had higher SBP association constants (Ka) for testosterone than did those of the II, III and IVA groups and controls. In contrast, the CBG concentrations in all the HIV+subjects were similar to those of the controls. However, the binding properties of HIV+CBG were abnormal: the Ka's for cortisol and 17 alpha hydroxyprogesterone binding were 50% below normal, while the number of binding sites was significantly higher. Such changes in these carrier proteins could result from conformational transitions; they may cause abnormal transfer of hormonal information and/or steroid hormones metabolism, thus modifying the impact of steroids on the immune response in HIV+subjects. PMID- 1430845 TI - DNA repair and Alzheimer's disease. AB - The accumulation of nonrepaired or misrepaired DNA lesions, induced by exogenous and/or endogenous DNA-damaging agents, has been postulated to be one of the major and fundamental causes of aging. The accumulation of DNA damage might lead to changes in the expression of genes important for cell survival and, as such, could be a relevant risk factor in the etiology of various age-related diseases, including neurodegenerative diseases. This review deals specifically with Alzheimer's disease (AD) and the proposed role of defective DNA repair in the etiology of this disease. The evidence that a genetic defect in some aspect of base excision repair is present in cells from AD patients is discussed. Based on the available data, it seems justified to conclude that in at least the familiar form of the disease such a DNA repair defect is present in fibroblast and lymphoid cells. The absence of sufficiently efficient DNA repair mechanisms, involved in the removal of small base damages in the brain, could result in the accumulation of misrepaired or nonrepaired DNA damage and might ultimately lead to the neuronal degeneration as observed in AD patients. In this respect, the existence of inherently imperfect DNA repair processes in longer-lived species, such as mammals, might be regarded as a trade-off between reproductive success and cellular maintenance and repair, which would lead to a high level of DNA damage and mutation at old age. PMID- 1430846 TI - Control of cell proliferation in senescent cells. PMID- 1430844 TI - The thymic education of developing T cells in self neuroendocrine principles. PMID- 1430847 TI - Effect of age on potassium- and tyramine-induced release of norepinephrine from cardiac synaptosomes in male F344 rats. AB - Potassium (K+)-induced norepinephrine (NE) release was examined in preparations of cardiac synaptosomes and sliced atria from 6-, 24-, and 26-mo-old male F344 rats. Cardiac synaptosomes were prepared from rat hearts by collagenase digestion followed by homogenization in 0.32 M sucrose and centrifugation. The synaptosome preparations and the sliced atria were labeled with 3H-NE and then placed in a superfusion system. K(+)-induced net fractional release of NE from synaptosomes prepared from 24- and 26-mo-old rats (4.3% and 3.0%, respectively) was significantly reduced when compared to NE release from synaptosomes from 6-mo-old rats (5.2%). K(+)-induced NE release from sliced atria from 24-mo-old rats (4.7%) was also significantly reduced when compared to NE release from atria from 6-mo old rats (6.3%). Perfusion of cardiac synaptosomes with buffer prepared without calcium (CA++free, < 5 microM) reduced K(+)-induced release by 50% in all age groups studied. Perfusion with tyramine induced identical rates of NE release from cardiac synaptosomes prepared from 6- and 24-mo-old rats. These results confirm that depolarization-induced NE release from cardiac sympathetic nerves is reduced in the old male F344 rat. PMID- 1430848 TI - Adipocytes of old rats produce a decreased amount of differentiation factor for preadipocytes derived from adipose tissue islets. AB - Adipose tissue of young rats (3.5 mo) contains cell formations ("islets") that, in culture, give rise to a variety of preadipocytes, or islet-derived cells (IDCs), that undergo rapid morphologic differentiation into adipocytes. Such adipose conversion depends on a differentiation-promoting factor produced by the mature adipocytes also present in the cultures. Here we report that cultured IDCs from epididymal fat of senescent rats (20 +/- 3 mo) show decreased adipose conversion compared to IDCs from 3.5 mo rats at 3 days of culture (14.2% vs 29.9%; p < .001). Both the number of co-cultured adipocytes and increased fragility with age were excluded as having a substantial role in explaining the decreased conversion. In order to determine whether the decrease differentiation of the IDCs of the old rats was intrinsic or due to reduced production of the differentiation factor by the old adipocytes, cross-over cultures of IDCs from young and old rats were grown in the presence of young or old adipocytes. When IDCs of old rats were cultured in the presence of young adipocytes, a significant twofold increase in differentiation was seen compared to old IDCs grown with old adipocytes (22.7% vs 10.3%; p < .001). This response was comparable to that of young IDCs grown with young adipocytes. Thus, old IDCs retain their ability to undergo extensive morphologic differentiation when appropriately stimulated. Reduced production of the differentiation-promoting factor by old adipocytes rather than the ability of IDCs to differentiate appears to be responsible for the decreased adipose conversion of IDCs seen in cultures of adipose tissue from senescent rats. PMID- 1430849 TI - Dietary restriction alters characteristics of glucose fuel use. AB - A longitudinal study of plasma glucose and insulin concentrations in ad libitum fed and dietary restricted male F344 rats was carried out. The life span diurnal pattern of plasma glucose concentration was such that through most of the day dietary restricted rats have significantly lower plasma glucose levels than ad libitum fed rats. Throughout the life span, dietary restricted rats maintain mean 24-hour plasma glucose concentrations about 15% below those of ad libitum fed rats. Plasma insulin levels are maintained in dietary restricted rats at about 50% of the levels in ad libitum fed rats. Although plasma glucose and insulin levels are lower, dietary restricted rats use glucose fuel at the same rate per unit of metabolic mass per day as rats fed ad libitum. While these findings are consistent with the glycation hypothesis of aging and with our hypothesis that dietary restriction retards the aging processes by altering the characteristics of fuel use, they do not establish the validity of either. It is possible that this effect of dietary restriction on carbohydrate metabolism plays no role in its antiaging action. Further studies are required to define the role of these altered characteristics of carbohydrate metabolism in the aging processes. PMID- 1430850 TI - Octogenarian subjects have low postprandial levels of chylomicron remnants: a possible explanation for protection against atherosclerosis. AB - Postprandial lipoprotein metabolism may play an important role in the development of atherosclerosis. It is widely believed that in healthy octogenarians, the atherogenic process occurs very slowly. In the present study, postprandial lipoprotein metabolism was examined in 14 octogenarian subjects (mean age, 84 +/- 4.2 years) and 19 younger controls (mean age, 50 +/- 4.8 years) using the vitamin A-fat loading test, in which intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Results indicated that mean peak chylomicron remnant RP levels and the areas below the chylomicron remnant RP curve were significantly lower in the octogenarian group than in the controls (625 +/- 329 vs 1321 +/- 688 micrograms/L and 3740 +/- 1078 vs 6162 +/- 1063 micrograms/L.h, respectively; p < .0001). No differences were found between the two groups in chylomicron RP levels or in lipolytic activity. The study suggests that octogenarians do not exhibit the decrease in chylomicron lipolysis that usually accompanies aging. In addition, these subjects have significantly lower levels of chylomicron remnants in the circulation. Since accumulation of these particles has been implicated in the development of atherogenesis, our findings may indicate a major mechanism of atherosclerosis prevention in healthy octogenarians. PMID- 1430851 TI - Effect of aging on circadian rhythm of atrial natriuretic peptide, plasma renin activity, and plasma aldosterone. AB - Atrial natriuretic peptide (ANP) shows a nychtohemeral fluctuation and an age related trend. The aim of this study was to explore the circadian rhythm of ANP as a function of age. Circadian rhythms of plasma renin activity (PRA), aldosterone (PA), and cortisol (PC) were explored as well. Twenty clinically healthy subjects, 10 young (20-25 yrs) and 10 elderly (65-75 yrs), were investigated, while recumbent, after synchronization to light-dark regimen and meal timing. Blood samples for RIA tests were collected six times during the 24 hr span. The chronobiologic analysis in young subjects demonstrated a significant circadian rhythm for all the investigated variables with an acrophase-timing located at 16.48 for ANP, 4.44 for PRA, 5.32 for PA, and 7.12 for PC. In elderly subjects we documented an important increase of 24-hr mean plasma levels but not a statistically significant circadian rhythm for ANP, and a decrease in mean value of PRA which maintained, however, a significant periodic 24-hr oscillation in parallel with PA and PC. The results in young subjects reinforce the concept that ANP plays physiologically an inhibitory role on the phasic secretion of renin. The lack of the circadian rhythm for ANP along with the divergent changes in ANP and PRA 24-hr mean concentration of elderly subjects both suggest that ANP exerts with advancing age only a counterregulatory role on the tonic rather than the phasic release of renin. PMID- 1430852 TI - Functional status and clinical findings in patients with Alzheimer's disease. AB - We analyzed the association of clinical findings with impaired functional status, i.e., activities of daily living (ADLs), in a sample of 240 patients diagnosed with Alzheimer's disease by NINCDS/ADRDA or DSM-III-R criteria. Logistic regression models were used to determine independent predictors of both the number of ADL impairments and number of ADL impairments characterized as moderate to severe. Two psychiatric problems, behavioral disorders and apathy, as well as a history of hypertension were significantly associated with ADL impairment independent of age, sex, race, and cognitive impairment. Behavioral disorders and apathy were also significantly associated with moderate to severe ADL impairment, but hypertension was not significant at this level. PMID- 1430853 TI - Incidence of depression in long-term care settings. AB - A one-year longitudinal study examined incidence and persistence of depression among nursing home and congregate apartment residents. Of 868 persons interviewed at Time 1, 15.7% displayed research-diagnosed possible major depression, and 16.5% displayed minor depressive symptoms. A follow-up interview a year later (T2; n = 448) yielded an incidence rate for possible major depression of 6.6% among persons with only minor or no depression in the previous year. For T1 nondepressives (i.e., excluding minor depressives), the incidence of possible major depression was 5.6%, and of minor depression, 6.3%. More than 40% of T1 possible major depressives showed no remission of symptoms a year later. In contrast, more than half of T1 minor depressives showed no depression at T2; however, another 16.2% appeared at follow-up to suffer possible major depression. Change in depression was associated with cognitive status, functional disability, and physical health. In general, persistence of depression was associated with greater decline, although patterns differed somewhat for the three functional indicators. Clinical and research implications of findings are discussed. PMID- 1430854 TI - Equations for predicting stature in white and black elderly individuals. AB - In an anthropometric nutritional assessment, elderly individuals are frequently unable to assume the positions needed for many measurements. This is especially true for stature, which is affected by mobility and skeletal deformities, and as a result measurements may be unreliable and inaccurate. An alternative is to use a surrogate value of stature. We developed predictive equations using data from elderly subjects in Cycle I of the National Health Examination Survey (NHES). The developed equations were cross-validated using two separate independent and more contemporary samples of elderly White men and women. The possible predictor variables were knee height and buttocks-knee length in the men and knee height and age in the women. For both the men and the women, the majority of the variance in stature was accounted for by knee height. Selected equation models were cross-validated, and a single equation was recommended for each elderly group that included knee height rather than buttocks-knee length as predictor variables. This selection was based upon the performance of the equations, and also upon the practical ease of collecting the possible predictor variables. Included with the recommended equations are the RMSEs and the standard error for predicting stature for an individual (SEI). The successful application of the recommended equations with two recent sets of elderly persons indicates the current utility of the recommended equations in White elderly Americans. PMID- 1430855 TI - Knee extensor and knee flexor strength: cross-sectional area ratios in young and elderly men. AB - The relationships between isometric and isokinetic-concentric knee extensor and knee flexor strength, and quadriceps and hamstring cross-sectional area (CSA) were determined in young (n = 13, M = 24.5y) and elderly (n = 12, M = 70.7y) men. Quadriceps and hamstring CSA was determined by computed tomography. Knee extensor and flexor strength at 0 degree/s and 120 degree/s was determined on a Kin-Com isokinetic dynamometer. Compared to the young men, elderly men had significantly smaller quadriceps muscles and were weaker (22-32%) in knee flexion and knee extension at both angular velocities. Strength:CSA ratios were similar at 0 degree/s, but elderly men had decreased ratios for both extensors and flexors at 120 degree/s. Correlations of knee extensor and flexor strength with muscle CSA were significant at both velocities in elderly men, but not at either velocity for the knee flexors in young men. The decrease in isometric strength in elderly men can be accounted for by their decrease in muscle CSA, but their decrease in isokinetic-concentric strength was greater than their loss of CSA. Further study is required to determine the reason for this nonproportional loss of isokinetic concentric strength. PMID- 1430856 TI - Attenuation of the cutaneous vasoconstrictor response to cold in elderly men. AB - This study tested the hypothesis that the cutaneous vasoconstrictor response to cold is reduced in elderly individuals. We measured laser Doppler flux (LDF) in the fingertip and blood cell velocity (CBV), via videodensitometry, in individual capillaries of the finger nailfold both before and during submersion of the contralateral arm in a 15 degrees C water bath. Subjects were 10 young (M = 25 years) and 10 old (M = 71 years) male adults. During the first minute of cooling, both the young (Y) and old (O) groups experienced a significant (p < .004) decrease in LDF. Over the subsequent 4 minutes of cold stress, LDF remained significantly depressed in the Y group, whereas LDF returned to values not significantly different from pre-cooling control in the O subjects. During the cold stress, CBV significantly decreased in the Y (p < .03) subjects; however, the degree of change was much less than that of LDF (49% decrease in LDF versus 14% decrease for CBV). In contrast to the Y subjects, the O group showed no significant change in CBV during cooling (p > .28). These results indicate that indirect cooling elicits a reflex decrease in cutaneous bloodflow, which is more pronounced in the deep vessels than in the superficial capillaries, and that these effects are attenuated with advancing age. PMID- 1430857 TI - Changes in grief and mental health of bereaved spouses of older suicides. AB - Comparisons are made of the impact of a suicide death on the surviving spouse (55 years and older) with that of a natural death on spouse survivors and a married nonbereaved control group over a bereavement period of 2 1/2 years after death. Regardless of mode of death, the loss of a loved one is a difficult psychological trauma, accompanied by depression, confusion, and pervasive feelings of emptiness. Few differences in the impact of the deaths in the early months of bereavement were reported, but changes appeared over the course of the 2 1/2-year measurement period. Compared with natural death survivors, the process of bereavement was found to be more difficult for the survivors of a suicide death, whose severe depressive feelings do not seem to lessen significantly and whose feelings of mental health do not seem to improve until after the first year. Women, in general, report greater feelings than men of anxiety, tension, and apprehension, especially within the first 6 months. By the end of the observation period, most of the differences between the two bereaved groups have disappeared, and both report functioning adequately despite continuing feelings of sadness and loss. PMID- 1430858 TI - Pain, activity restriction, and symptoms of depression among community-residing elderly adults. AB - Relations among physical illness, functional disability, pain, and symptoms of depression were investigated in a sample of community-residing elderly outpatients. As expected, physical illness, functional disability, and pain were correlated with depressive symptomatology. It was further hypothesized that functional disability (but not physical illness per se) would attenuate the relation between depressed affect and pain. The data supported these predictions by showing that functional disability (but not physical illness) accounted for differences in reported pain between nondepressed subjects and those at risk for developing clinical depression. Additional analyses revealed that functional disability mediated relations between pain and depressed affect and also between illness and depressed affect. These results indicate that both pain and illness are important contributors to functional disability, which in turn contributes to symptoms of depression. Secondary analyses revealed that restriction of certain activities associated with physical mobility and independence were strong individual factors in attenuating the relation between pain and depressed affect. An important implication of this research is that neither pain nor activity restriction should be treated in isolation. Maximal effects are likely to be achieved when both are targeted simultaneously. PMID- 1430859 TI - Determinants of change in perceived health in a longitudinal study of older adults. AB - To determine the factors that are predictive of a negative decline in perceived health in a longitudinal study of 251 men and women aged 62 and older, we developed a "synthetic" cohort of individuals who experienced a decline in perceived health between two time points and a control cohort of those who did not. The longitudinal design of the study made it possible to evaluate the effects of "baseline" predictors, gathered prior to the time interval during which the reported change in perceived health occurred, in addition to measures assessed at the two time points between which the change in health was reported. Hierarchical logistic regression models were used to examine the effect of demographic, psychosocial, and illness measures on change in perceived health. These analyses revealed that increases in new illnesses, increased physician visits, and worsening of preexisting conditions (in subjects who had higher feelings of self-efficacy) were all associated with a decline in perceived health, after controlling for the effects of baseline illnesses and medication use. After accounting for these effects of changes in objective illness indicators, we found that changed psychosocial factors also predicted a decline in perceived health. Lower life satisfaction and higher depression at baseline were predictive of a later decline in perceived health. In addition, data collected at the third consecutive time point were evaluated to assess determinants of a sustained vs transient decline in perceived health. A sustained decline in perceived health was associated with increased depression and decreased self-efficacy. PMID- 1430860 TI - Self-recognition in Alzheimer's disease: a mirror and video study. AB - Twenty-nine subjects with Senile Dementia of the Alzheimer Type (SDAT) were tested for self-recognition when confronted with their reflection in a mirror and with a noncontingent video image. All subjects at stage 5 (moderately severe cognitive decline) on the Global Deterioration Scale (GDS) showed self recognition in the mirror condition, whereas 25% of GDS stage 6 subjects (severe cognitive decline) did not self-recognize. Only seven subjects showed signs of self-recognition on video (six at GDS 5, one at GDS 6). The results confirm two hypotheses: the first, based on studies with infants, is that contingency cues in the mirror condition facilitate self-recognition; the second is that SDAT patients may show "regression" of at least some cognitive functions. PMID- 1430861 TI - A comparative analysis of functional status among Spanish- and English-speaking patients with dementia. AB - The assessment of functional capacity is regarded as an important part of a comprehensive diagnostic work-up for dementia. However, there is a paucity of data regarding comparative functional performance among different ethnic/cultural groups. In this study, we compared Spanish- and English-speaking dementia patients and normal controls on a comprehensive functional assessment battery administered within the clinical setting. Despite equivalent levels of cognitive impairment, Spanish-speaking dementia patients evidenced more difficulties on certain functional tasks relative to their English-speaking counterparts. On the other hand, Spanish- and English-speaking controls did not differ with regards to their functional performance. Results suggest that the extent of deterioration in specific functional subskills may be related to the degree to which they have been overlearned and practiced. Further, they indicate the potential utility of direct functional assessment in both Spanish- and English-speaking populations. PMID- 1430862 TI - Event-related potential correlates of repetition priming and stimulus classification in young, middle-aged, and older adults. AB - Electrophysiological and behavioral measures were concurrently recorded from young, middle-aged, and elderly subjects during two classification tasks that required different levels of processing. In both tasks, a portion of stimuli repeated after lags of 2, 8, and 32 intervening items following their first presentation, although these repetitions were incidental to the primary task. All three age groups showed similar patterns of behavioral and event-related potential (ERP) responses associated with stimulus classification and item repetition. ERPs to repeated words were characterized by greater positive amplitude relative to words at first presentation. Similarly, ERPs elicited by items in a primed category were more positive compared with unprimed items. Reaction times were faster to both repeated and primed items. Behavioral and ERP effects were more marked when subjects were required to discriminate items based on meaning rather than on orthography. This study supports previous behavioral evidence suggesting that processes associated with repetition priming and stimulus classification are preserved with age, and demonstrates that ERPs are responsive to repetition throughout the life cycle. Implications for the cognitive processes underlying repetition effects are also discussed. PMID- 1430863 TI - Effects of aging and schedules of knowledge of results on motor learning. AB - Little research has been conducted on aging and the learning of motor skills. In this study, we examined the effects of different schedules of knowledge of results (KR) on the acquisition and retention of a movement timing task by young adults (20-23 years) and older adults (60-82 years). The results indicated that there were differences between young and older adults in the accuracy and consistency of motor performance when KR was provided. Accuracy effects persisted during a retention interval when KR was no longer provided, although there were no differences in variability. There were no interactions of age with any of the KR-related variables. These findings suggest that the ability to process KR, and the effects of KR on motor learning, are similar in young and older adults. These findings are discussed in terms of age-related issues in movement control and learning processes. PMID- 1430864 TI - Antecedents and dimensions of religious involvement among older black adults. AB - This study proposed and tested a measurement model of religiosity among a sample of older (55 years of age and above) Black Americans. This model incorporates three correlated dimensions of religious involvement, termed organizational, nonorganizational, and subjective religiosity. Findings indicate that the proposed model provides a good fit to the data, is preferable to other alternative models, and exhibits convergent validity with respect to exogenous or antecedent variables (age, gender, marital status, income, education, urbanicity, and region) known to predict religious involvement. In addition, these antecedents exhibit stronger effects on subjective religiosity than on the two more behavioral dimensions of religiosity. Interpretation of these status-group differences in religiosity focuses on socialization experiences and social environment factors which may promote a religious world-view. PMID- 1430865 TI - Acculturation and psychological distress in three groups of elderly Hispanics. AB - The goal of this study was to evaluate the relationship between acculturation and psychological distress in three groups of older adults who have immigrated from Mexico, Cuba, and Puerto Rico. Financial strain and social isolation are specified as intervening mechanisms that are thought to link acculturation with well-being in late life. Data from a recent nationwide survey of older Hispanics suggest that levels of psychological distress tend to vary across Hispanic groups and that these differences may be attributed in part to the complex interplay between educational attainment, language acculturation, financial strain, and social isolation. PMID- 1430866 TI - Family structure and changes in living arrangements among elderly nonmarried parents. AB - We used Longitudinal Study of Aging data to investigate change between 1984 and 1986 in living arrangements of older nonmarried parents, focusing on transitions from living alone and living with children to living alone, with children, with others, and institutionalization. Predictors reflect opportunities for coresidence (number and gender of children), resources, needs, and (indirect measures of) attitudes. We find that those with more children are more likely to change from living alone to living with a child. However, number of children does not affect the odds of moving from living with a child to other arrangements (including institutionalization). Gender of children does not affect tendencies to begin coresidence, although there is slight evidence of more movement out of coresidence for those with sons. Findings are interpreted in terms of the influence of adult children's and parents' needs in determining coresidence. PMID- 1430867 TI - New cohorts of urban elders: are they in trouble? AB - Recent social and economic trends suggest that the health and welfare of elderly persons living in urban areas may have deteriorated during the past two decades. Two representative samples of noninstitutionalized urban persons aged 65 and over were interviewed, one in 1975 (n = 1598) and the other in 1987 (n = 1491). Cohorts of "young-old" (ages 65-76), "old-old" (ages 77-88), and "oldest-old" (ages 89-100) urban residents were compared at the two time points by multivariate analysis. Over the 12 years studied, the proportion of Blacks and poor persons rose, while the educational level improved. The young-old cohort of 1987, in particular, reported more chronic illness, more psychological distress, more need for help with activities of daily living, more visits to physicians, and more need for additional medical care. We conclude that, between 1975 and 1987, a new cohort of urban residents who were more impaired, disabled, and disadvantaged than their predecessors entered the young-old age group. PMID- 1430868 TI - Perceived health status and mortality among older men and women. AB - This article separately examines the relationship of perceived health status and mortality for the 1,599 men and 2,904 women self-respondents in the Longitudinal Study on Aging. Using hierarchical logistic regression, the zero-order relationships are decomposed by the serial introduction of demographic, socioeconomic, health status, and psychosocial factors. For men, only those in poor health are significantly more likely to die than those in excellent health (adjusted odds ratio = 1.754), all other things being equal. For women, those in fair or poor health are more likely to die than those in excellent health (adjusted odds ratios = 1.870 and 2.181, respectively), all other things being equal. PMID- 1430869 TI - Refusal rates in a longitudinal study of older people: implications for field methods. AB - Use of a carefully designed refusal conversion protocol at first follow-up in a longitudinal study of a representative sample of over 4,000 older people was investigated. Respondents who refused initially did not differ from respondents by age or gender but were more functionally independent, citing disinterest most frequently as the reason for refusal. The protocol was successful in convincing 43 percent of these initial refusals to continue participation, but less successful with proxy respondents (27% converted). Most of the refusals that were converted were done by telephone at minimal cost. Results show that it is possible, given appropriate field methods, to retain the very old and disabled in longitudinal studies. PMID- 1430870 TI - Breast cancer screening in older women: overview. PMID- 1430871 TI - Breast cancer screening among older racial/ethnic minorities and whites: barriers to early detection. AB - Screening mammography for early detection of breast cancer has been shown to be an effective method for reducing mortality in older women. Based on the results from the 1987-88 National Health Interview Survey, older minority women have low prevalence rates of screening mammography. Among women aged 75 and older, 83.5% of Black women, 93.2% of Hispanic women, and 75.0% of White women have never had a mammogram. On the average, about 12% of minority women over the age of 65 have had a screening mammogram within the preceding year, compared with about 15% of White women. Among women 75 + years of age, Black and Hispanic women had markedly lower rates of clinical breast examination in the last year (23.4% and 20.5% respectively) as compared to White women (35.2%). The most common reason for not having a mammogram among Black women 65 years of age and older was that the doctor did not recommend a mammogram. For Hispanic and White women in this age group, the most common reason was that a mammogram was not needed or not necessary. Aggressive and creative breast cancer screening activities for minority aged 65 and older are clearly indicated. PMID- 1430872 TI - Physician-related barriers to breast cancer screening in older women. AB - Despite evidence that annual mammographic screening in women 50 years and older reduces mortality, surveys of physicians and patients have repeatedly demonstrated that annual screening mammography is not performed. The fundamental question addressed in this chapter is: If the assumption is made that the scientific evidence supports the use of mammography, what, then, are physician related barriers to mammographic screening of elderly women? Using a model that classifies barriers to implementing prevention protocols into three categories (predisposing, enabling, and reinforcing factors), literature is reviewed to help identify reasons for low mammographic screening rates, especially in elderly women. This article concludes with a discussion of strategies that may help overcome barriers to mammographic screening in elderly women. PMID- 1430873 TI - Breast cancer screening in older women: ethical issues. PMID- 1430874 TI - Breast cancer screening in older women: the family practice perspective. AB - This article reviews screening for breast cancer in older women from the perspective of the primary care physician. Although breast cancer is a leading cause of cancer in women, the diagnosis of breast cancer in an asymptomatic woman is an uncommon occurrence for the individual physician. Physician compliance with breast cancer screening recommendations is less than optimum: physicians report higher compliance in survey studies than is demonstrated by performance audits. The low yield of screening, cost concerns, concerns about the reliability of radiology reports, concerns about patient compliance, lack of time, and forgetfulness are reasons cited for poor provider compliance with screening recommendations. In general there is no reason not to recommend mammography for older women unless individual factors including biologic age, life expectancy, comorbidities, or patient preference appear to make screening not worthwhile. The decision to stop recommending mammography for an older woman should be made in conjunction with the patient. PMID- 1430875 TI - Breast cancer screening in older women: the geriatrician/internist perspective. AB - There are many issues of concern to internists and geriatricians as they face the prospect of implementing breast cancer screening programs for elderly women. Population heterogeneity and variations in comorbidity require individualization in order to maximize benefit. Decision making is complicated by family interactions, especially for patients with altered cognition. The time it takes to perform exams and discuss possibilities in a busy office practice may be inhibitory. Internists will want to see more definitive data on efficacy, specifically in women > age 70, but patients in this age cohort may actually rely on physicians' recommendations to a greater extent than younger cohorts. PMID- 1430876 TI - Breast cancer screening in older women: the consumer perspective. AB - Fear of cancer and weak support from physicians make it difficult to encourage women to have regular mammograms. An effective campaign of broad mammography screening should be aimed at both health professionals and women. Essential to this screening is a public policy that establishes public and private insurance coverage. Barriers, including high cost, must be eliminated. Effective organization can succeed in reaching more older women for screening. Rationing breast cancer screening, at a time when the incidence of breast cancer is increasing, violates fundamental beliefs in equality and justice. Proposals to limit or to expand screening require a defensible and supportable rationale. Health professionals should not decide for patients whether they should have a mammogram and what treatment is best. The physician should counsel and assist the patient or the surrogate to decide on an appropriate plan of care. PMID- 1430877 TI - Decision making and the principles of screening for breast cancer. AB - This position paper raises issues central to the screening process and how it relates to breast cancer in the elderly. These comments reflect neither a formal model developed specifically for breast cancer screening nor detailed data about this disease. Such information is available elsewhere in these Forum proceedings. Rather, this discussion develops the general principles of screening as they impact on breast cancer in elderly women. PMID- 1430878 TI - The biology of breast cancer in older women. AB - The incidence of breast cancer among women older than 65 years of age is 1.7 times higher than the rate for women 45 to 64 years of age, and 10 times higher than for women younger than 45. In addition, the relative survival from breast cancer is decreased among elderly women. Although elderly women more frequently present with advanced breast cancer, the incidence of other poor prognostic factors generally associated with early disease recurrence and short survival is not increased among the elderly compared to younger women. Most breast tumors from elderly patients contain estrogen receptors and progesterone receptors and would be expected to respond to hormonal therapies, and most tumors have low proliferative rates which would be indicative of slow-growing, indolent tumors. Several studies have documented that elderly women often do not receive complete workups for definitive staging of their breast cancer, and that even after adjustment for comorbid conditions, elderly patients are less likely to receive optimal standard therapy for their disease. PMID- 1430879 TI - Comorbidity and functional status in older women with breast cancer: implications for screening, treatment, and prognosis. AB - This is a review of research on the effects of comorbidity and functional status on breast cancer diagnosis, treatment, and prognosis in older women. The objective is to summarize results from recent studies and recommend directions for future research (a) to develop more precise guidelines for breast cancer screening, and (b) to identify and eliminate barriers preventing the attainment of those guidelines. Research is needed to determine more clearly how comorbidity and functioning affect screening practices and stage of disease at diagnosis. There is evidence that comorbidity explains, in part, why older women receive less invasive therapy. It is unknown, however, whether these treatment decisions improve quality or duration of survival. Although it is evident that comorbidity and disability adversely affect survival, research is needed to examine the etiology, course, and effects of specific combinations of conditions. Final recommendations include using the Established Populations for Epidemiologic Studies of the Elderly (EPESE) and the Surveillance, Epidemiology, and End Results (SEER) programs to address a number of these questions. PMID- 1430880 TI - Demographics (1950-1987) of breast cancer in birth cohorts of older women. AB - The effects of screening on breast cancer mortality, incidence, and prevalence were investigated using a general forecasting and simulation model. First, a biologically motivated model of disease incidence and mortality was fit to the breast cancer mortality experience of 15 U.S. White female birth cohorts followed for a 38-year period. The model assumed that breast cancer was the result of two different diseases. The first, or "premenopausal" disease, tends to have strong associations with the family history of disease and to be histologically more aggressive. The second, "postmenopausal" disease, occurs at more advanced ages, is apparently less strongly linked to family history, and is less aggressive with different histological characteristics (e.g., positive estrogen receptor status). Those results were used to forecast the effects of screening on the stage at diagnosis to simulate a screening program which reduced late-stage diagnoses by 50%. This produced large reductions in breast cancer mortality--an impact larger for disease associated with late age of onset. PMID- 1430881 TI - Mammography for older women: who uses, who benefits? AB - In order to juxtapose the health, social, and behavioral factors associated with use of screening mammography with short-term mortality among elderly women, we analyzed the NHIS Cancer Epidemiology Supplemental Survey and the Longitudinal Study of Aging. After controlling for sociodemographic factors, having a usual source of care of and knowledge of screening guidelines, we found that a woman's health status is unrelated to having had a screening mammogram. Analyses of the LSOA, however, revealed that health factors were strongly related to 4-year mortality, particularly among women 75 and over. As it is unlikely that the subpopulation of older women who are at high risk of death within 4 years will benefit from a program of universal screening, outreach program messages and physician education programs should probably be designed to proactively recruit those most likely to benefit. PMID- 1430882 TI - Screening recommendations of the forum panel. PMID- 1430883 TI - Economic considerations in breast cancer screening of older women. AB - The incidence of breast cancer increases with age, tending to result in more favorable cost-effectiveness outcomes with more advanced age of the screened population. On the other hand, the decreased remaining life expectancy of older women can be expected to reduce the cost effectiveness of screening. To assess these competing factors, the cost effectiveness of a long-term breast cancer screening program was evaluated using a computerized simulation model. The cost per life year saved decreased when the 65-69 year age group was added to a program screening women aged 50-64. For older age groups, however, cost effectiveness became relatively less favorable. The cost per life year saved of screening the 80-84 year age group was 55% higher than for the 65-69 group. PMID- 1430884 TI - Screening mammography in women over age 65. AB - Routine screening by mammography and physical examination can detect breast cancers earlier at all ages. In women over age 65 the sensitivity of mammography is increased, and the positive predictive value for mammography is higher than in younger women. There are no direct data that can be used to determine at what age screening is no longer of value. This question must be evaluated on an individual basis and should take into account the quality of life and competing causes of death. The medical benefit from screening for a given individual should be considered separately from society's cost/benefit goal to reduce health care expenditures, because the two are likely to produce contradictory recommendations. PMID- 1430885 TI - Physical examination of the breasts in screening for breast cancer. AB - No currently available evidence from breast cancer screening studies provides strong justification for the implementation of screening in elderly females. Because it is an absence of evidence rather than negative evidence which pertains, it is concluded that if screening is introduced it should include both mammography and clinical examination of the breasts because the two complement one another. As well, stringent quality control procedures are required for both modalities. It is possible that clinical examination of the breasts performed by a nurse-examiner will enhance compliance with screening schedules. PMID- 1430886 TI - The efficacy of breast self-examination. AB - Literature related to the efficacy and to the definition and measurement of breast self-examination (BSE) is reviewed with particular attention to its relevance for women over 65. Overall, data on the efficacy of BSE suggest that it has a small but measurable impact on earlier detection of breast cancer as measured by clinical stage and tumor size and sometimes by pathological stage. The largest differences are between some BSE and no BSE. An analysis of BSE suggests that instructions could be simplified for older women in order to increase the reliability and acceptability of the examination. A research agenda is proposed which includes (a) testing BSE instructions tailored for older women, (b) studying the intervening steps between BSE and cancer diagnosis, (c) testing methods to increase acceptance by older women, and (d) investigating the relationship between BSE and earlier detection of breast cancer in older women. PMID- 1430887 TI - Supporting statements and rationale. PMID- 1430888 TI - Breast self-examination in women 65 and older. AB - Studies of breast self-examination (BSE) in older women have revealed deficiencies in both frequency and proficiency of practice. Current data from an ongoing study indicate that practice is sufficiently poor as to make the detection of lumps difficult. Interventions to increase frequency and proficiency, however, have been encouraging. Several studies are reporting significant improvement in practice following specific strategies. Barriers such as forgetting and embarrassment need to be addressed when attempting to increase frequency and proficiency. The efficiency of BSE cannot be adequately addressed until women are trained at a proficient level. PMID- 1430889 TI - Efficacy of screening for breast cancer in older women. AB - The effect of screening on mortality from breast cancer has been evaluated in four intervention (experimental) studies with random assignment, one intervention study with nonrandom assignment, three case-control studies, and one follow-up study. Each of these studies showed a beneficial effect of screening among women who were at least 45, 50, or 55 years old at entry, but there is almost no information available on the value of screening women more than 74 years old. The data are not helpful in choosing a screening interval within the range 12-33 months, or in deciding whether to screen by mammography and palpation combined or by mammography alone. Additional issues in screening very old women are the delay before the effect of screening appears, the high mortality from causes other than breast cancer, and the effect of previous screening. PMID- 1430890 TI - Older women's participation in breast screening. AB - The incidence of breast cancer increases with age, but women's participation in breast screening decreases with age. National and regional surveys indicate a number of barriers. Women over age 65 are more likely to say they have never heard of mammograms, that they did not know they needed them, and that their doctors did not recommend them. In a study conducted at Fox Chase Cancer Center, in Philadelphia, participation in an HMO-sponsored breast screening program appeared to reverse the usual age-related decrease in mammography. If mammography utilization is to increase in women over age 65, physicians must offer unambiguous referrals to older women. In addition, health education interventions are needed to improve knowledge and beliefs of older women and their physicians. And, finally, strategies also are needed to enhance access. With the advent of Medicare coverage, payment will be less of a barrier. But other barriers remain. PMID- 1430891 TI - A qualitative study about breast cancer screening in older women: Implications for research. AB - Focus groups were used to explore a range of issues concerning breast cancer screening in elderly women and to contribute to defining a research agenda. Two groups consisted of women aged 65-75 and 75 and older, and one group consisted of primary care physicians. Predominant topic areas were women's awareness of breast cancer and screening information, attitudes and perceived barriers to screening (including those related to women themselves, to the health care system, and to physicians), issues related to relationships within the medical community, and opinions about and priorities for change. PMID- 1430892 TI - Culture, environment, and restraints: a conceptual model for research and practice. AB - 1. Despite its importance to the care of the elderly, little research has focused on the effects of the environment on health and well-being. 2. It is hypothesized that environmental factors, including cultural attitudes and beliefs of nursing home staff, contribute to restraint of nursing home residents. 3. Nurses can be instrumental in creating a nursing home culture that values a restraint-free environment. PMID- 1430893 TI - Reducing physical restraints: developing an educational program. AB - 1. Philosophical premises for an educational program aimed at restraint reduction include beliefs about quality of care, commitment to understanding the meaning of behavior, and desire to shift practice from control of behavior to individualized approaches to care. 2. If change is to occur, an educational program aimed at restraint reduction must recognize the potential contributions of all staff members, use an interactive teaching style, and promote discussion and problem solving. 3. Results of testing a Restraint Education Program suggested that altering staff beliefs and increasing knowledge produced a change in restraint practices, at least in the short term. PMID- 1430894 TI - A century of progress: today's strategies for responding to wandering behavior. AB - 1. In an effort to protect wanderers, nurses have overused physical restraints. Such practices have been reinforced by the potential for lawsuits charging negligence when wandering results in negative outcomes. 2. Wandering is movement changing over time and, thus, is a nonlinear ultradian rhythm, with locomoting and nonlocomoting phases. As a rhythm, an individual's wandering pattern is stable over a 1-week period. 3. Because most travel is direct, most ambulation, even for known wanderers, may not be wandering at all. Among inefficient travel patterns, lapping was the most frequently observed. 4. Behavior modification, grids, camouflage, and other environmental interventions are preferable to chemical or physical restraint in attempting to reduce unwanted or unsupervised exits by wanderers. These methods are not fail-proof, however, and do not replace careful supervision of wanderers by personnel. PMID- 1430896 TI - Falls in the nursing home: preventable or inevitable? AB - 1. Falls in the elderly are frequent occurrences and are usually a result of the complex interaction of environmental, physiological, and pathological variables. Fall-related injuries happen much less frequently. 2. Physical restraints have not been found effective in preventing falls and may be associated with increased risk of fall-related injury. 3. Because of the complex nature of falls in the elderly, fall prevention programs must emphasize the critical assessment of each resident's risks for falling with targeted interventions. PMID- 1430895 TI - Goal-directed care: caring for aggressive nursing home residents with dementia. AB - 1. Aggressive behavior in elders with dementia occurs most often during personal care. It is often a response to invasion of private space and may be prevented or reduced by interpersonal approaches that reflect a set of individualized goals for the resident. 2. Five resident goals for preventing or reducing aggressive behavior are to feel safe, to feel physically comfortable, to experience a sense of control, to experience optimal stress, and to experience pleasure. 3. These goals provide a framework for humane care that respects the personhood of the individual and minimizes the need for psychotropic medications and physical restraints. PMID- 1430897 TI - Restraint strategies: reducing restraints in Oregon's long-term care facilities. PMID- 1430898 TI - Methods to reduce restraints: process, outcomes, and future directions. PMID- 1430899 TI - Correlates of self-care among the independent elderly: self-concept affects well being. AB - There was a significant positive correlation between self-care and self-concept, suggesting that psychosocial interventions that enhance an older person's self concept may be expected to improve self-care and, conversely, that participation in self-care activities may be expected to strengthen self-concept. Although functional health status was not significantly correlated with self-care, it was related to self-concept, suggesting either that functional health has a role in maintaining self-concept among older persons or that self-concept positively contributes to functional health status. Self-concept and self-care can be enhanced in older persons by communicating respect and demonstrating caring behaviors, reinforcing health-promoting behaviors, encouraging activities of daily living that contribute to independence, and by avoiding a focus on self care deficits. PMID- 1430900 TI - An exploratory study: assessing the meaning in life among older adult clients. AB - Meaning in life has been intimately linked to health, but it has not been explored in an elderly population. The factors that elderly people perceive as being meaningful must be identified, as well as the extent to which they experience fulfillment of meaning in their lives. The majority of study participants indicated that relationships give meaning to their lives; however, nurses must individually assess clients regarding what is most meaningful to them. Clients without meaning or low levels of meaning need to be identified. As nurses become more aware of what is meaningful to older people, they can plan and carry out interventions based on interaction to support or improve areas meaningful to the older person. PMID- 1430901 TI - Skin problems: epidemiology of pressure ulcers in a skilled care facility. AB - The majority of nursing home residents have conditions that place them at risk for the development of pressure ulcers. Reported pressure ulcer prevalence rates range from 16% to 35%. Pressure ulcers are multifactorial in origin and necessitate ongoing vigilance by the entire health-care team. Associated risk factors include impairments of circulation, sensation, physical condition, nutrition, mobility, and activity. Stage I pressure ulcers frequently go unrecognized, yet their recognition is essential to prevent further damage. Comprehensive initial assessments of the skin and risk factors of pressure ulcer development at admission will allow for easier reassessment and comparison. PMID- 1430902 TI - Phantom of the nursing home. PMID- 1430903 TI - Diagnostic dilemma: cognitive impairment in the elderly. AB - Cognitive impairment is a significant health problem for the elderly and is associated with severe negative consequences: higher morbidity and mortality and a diminished capacity to care for self. The accurate diagnosis of acute confusion, dementia, and depression depends on the routine, systematic, and comprehensive assessment of cognition, best achieved through the use of a mental status questionnaire and a behavioral rating scale. Nonspecific clinical features, atypical and variable presentations of symptomatology, and the frequent coexistence of acute confusion, dementia, and depression make an accurate diagnosis of the specific form of cognitive impairment difficult. The primary cognition disorder in acute confusion is that of attention, memory with dementia, and mood with depression. PMID- 1430904 TI - [Rights and duties of the fetus. Pediatric contribution to the resolution of moral dilemmas in the prenatal medical practice]. PMID- 1430905 TI - [Post-menopausal osteoporosis. Epidemiologic aspects]. AB - The purpose of this study is to point out the epidemiological features concerning the frequency and seriousness of post-menopausal osteoporosis, and concerning screening and prevention of osteoporotic fractures. Osteoporosis is a condition very widespread, characterised by fragility fractures. It has been estimated that in France one million of women suffer from vertebral fractures. Osteoporosis can alter the quality of life in various ways. Its cost is high, representing 4 billions francs a year in France only for hip fractures. The only preventive treatment that has been agreed on universally is oestrogen therapy. The fact that this treatment is not systematically recommended does not explain that only 8% among french menopausal women take oestrogen. The factors available at present to identify women at high risk of osteoporotic fractures are risk factors evaluated by clinical history, biological markers of bone formation and measurements of bone mass. None of these risk factors have enough sensibility and specificity to define accurately risks groups. Furthermore it is necessary to specify the effects of treatments associating oestrogens and progestogens prescribed in France, in particular effects on the risks of cardio-vascular diseases and breast cancer. PMID- 1430906 TI - [Breast cancer associated with pregnancy. Nine case reports. Review of the literature and current update]. AB - The authors report nine personal cases in a review of the literature concerning cancers of the breast associated with pregnancy and lactation (until a year post partum). The diagnosis of the illness is reported to be difficult in pregnant women and it is necessary to use fully all the diagnostic procedures available and in particular cytology and histology. Surgery is urgent. It is classical practice to carry out a mastectomy with axillary clearance. Nevertheless more conservative treatments are now being suggested. The principal problem of therapy is linked to the effects of adjuvant therapy on the fetus be they radiotherapy or chemotherapy, particularly because it is very important that treatments should be thorough and start early in the pregnancy. The overall prognosis is bad because pregnancy seems above all to aggravate serious forms of the disease. PMID- 1430907 TI - [An original model of experimental endometriosis in the rabbit]. AB - An attempt to create experimental endometriosis in the rabbit by the usual technique was tried on eight animals. It was disappointing. A new technique which is easier to carry out implanting endometrium was suggested. The results were evaluated in 57 animals. The technique proved to be easier and more reliable. The technique cannot be used unless the animal has been through puberty. PMID- 1430908 TI - [Prognostic value of preovulatory elevations of plasma progesterone during in vitro fertilization using LHRH agonists in a long protocol]. AB - We retrospectively analyzed the prevalence and prognostic significance of plasma progesterone rises during in vitro fertilization (IVF) protocols including pituitary down-regulation by LHRH agonists in a long protocol and stimulation by hMG (n = 1,116: Group A) or pure FSH (n = 178: Group B). On the day of hCG injection, plasma progesterone level was in the 0.60-0.99 ng/ml range in 7.1% of group A patients and 6.2% of group B patients (NS) and above 1 ng/ml in respectively 4.0% and 3.4% of the cases (NS). On the same day, plasma progesterone was strongly correlated with plasma estradiol (r = 0.26 - p < 0.001 in group A; r = 0.21 - p < 0.01 in group B). However, increased progesterone levels were not associated with changes in plasma LH levels, falls in plasma estradiol levels after hCG injection, or significant modifications in biological and clinical results of IVF. The cause of this pattern of progesterone rise remains to be elucidated. PMID- 1430909 TI - [Turner's syndrome and pregnancy in donor oocytes and in vitro fertilization. Three case reports]. AB - It is extremely rare for pregnancy to occur spontaneously in a woman with a mosaic or non-mosaic karyotype 45 x 0. (Till now only 13 patients with a homogeneous x 0 karyotype have been reported out of 62 patients who between them have had 138 pregnancies). Furthermore these pregnancies have been plagued by a number of important complications or fetal malformations (21% have had chromosome anomalies). It is therefore clear that in vitro fertilization with donor oocytes is a tempting solution for these women. The authors having three personal cases try and point out the conditions under which this technique can be used. It is important to realise that from the age of 10 or 12 years these patients have to have hormone treatment in order to avoid hypoplasia and hypovascularization of the uterus. Those conditions explain why so many these women had premature labours and also suffer from pre-eclampsia. Caesarean section was often found to be necessary because of feto-pelvic disproportion. PMID- 1430910 TI - [Intramural pregnancy: a case report]. AB - Implantation into the muscle wall is one of the rarer forms of ectopic pregnancy. We report an uncomplicated case which was discovered during therapeutic termination of pregnancy at 10 weeks. We point out how valuable the use of ultrasound during the operation is for making the diagnosis when suction does not provide adequate quantities of products. PMID- 1430911 TI - [Role of vaginal echography in the investigation of menorrhagia and metrorrhagia in the reproductive years]. AB - Eighty non-menopausal patients who had troubles of menorrhagia or metrorrhagia who were neither pregnant nor had cervical pathology, were investigated first by vaginal ultrasound and then by hysteroscopy. In 43 of the cases a hysterosalpingogram had been carried out before hand. All patients had histological examination of tissues. The main pathological ultrasound features were clearly made out. Vaginal ultrasound, and the conditions under which the study was undertaken, gives much more information than hysterosalpingography and will be able in future to a greater extent, to replace conventional radiography. Vaginal ultrasound manages to achieve information about the endometrium and the uterine cavity almost equal to that obtained by hysteroscopy and furthermore it gives more precise information about the state of the myometrium. Vaginal ultrasound therefore seems to be an excellent first stage examination to investigate menstrual disturbances in reproductive life, and so long as it is carried out under good conditions will limit the indications for hysteroscopy and will be able to indicate when it is necessary to carry out simple exploratory hysteroscopy or operative hysteroscopy. PMID- 1430912 TI - [Technique and preliminary results in second-look laparoscopy in epithelial malignant ovarian tumors]. AB - Second-look laparotomy is the usual mean of intraperitoneal evaluation in patients treated for ovarian carcinoma. We present a preliminary study of 33 second-look. Thirteen of these procedures were performed by laparoscopy. Because of previous surgical history a specific technique is necessary including safety tests, cytologic evaluation after peritoneal washing, and biopsies of any abnormal peritoneal areas, original tumors sites and normal appearing peritoneum. In order to achieve the evaluation of the entire peritoneal cavity a complete bowel adhesiolysis is required. For trained laparoscopists the surgical complication rate is low. In this preliminary study we found that prognosis following negative second-look laparoscopy and second-look laparotomy are similar, suggesting that laparoscopy is a valuable alternative to laparotomy for second-look evaluation in ovarian cancer. PMID- 1430913 TI - [Prenatal screening for cysts of choroid plexus. Evolution and interpretation of 30 cases]. AB - The authors report thirty cases in which they diagnosed a cyst of the choroid plexus antenatally between the 18th and the 36th week of amenorrhoea (mean 21 weeks). Choroid plexus cysts show up in some pictures as round or oval cysts clearly visible in the region of the choroid plexus. They appear in the lateral cerebral ventricles. They frequently occur between the 15th and 25th week of amenorrhoea (0.6 to 2.5% of pregnancies), unilaterally or bilaterally (46%) either on the right of left side and varying in size (3 to 20 mm). These characteristics do not influence the way they evolve. If a single choroid plexus cyst is found a control ultrasound should be carried out four weeks later. 96% of them have disappeared by the end of the second trimester; but if they do persist in the third trimester (4%) they are not necessarily pathological. On the other hand if a choroid plexus cyst is associated with some other morphological biometric abnormality antenatal chromosome testing should be carried out because trisomy 18 is more common in this situation (4.8%) than in the general population. PMID- 1430914 TI - [Cerebral hemorrhage in utero. Diagnosis and management. A case report]. AB - The authors report a case of massive intracerebral haemorrhage which was diagnosed in utero by ultrasound. The ultrasound of the brain showed a total disorganisation of all known structures with the appearance of unhomogeneous zones spread across both hemispheres and including a large dilatation of the ventricles. Transcervical puncture of the fontanelle allowed the delivery of a stillborn child without other congenital abnormalities. CMV infection was thought to be the cause. A review of the literature shows that there are different ways of treating this conditions depending on the ultrasound appearances. The prognosis must be very guarded and depends on the aetiology. PMID- 1430915 TI - [Preliminary study on the variability of the fetal cerebral velocimetry in various vessels of the Circle of Willis]. AB - The authors have tried to analyse in a small series, the possibility as well as the variability of blood flow velocity waveforms in the different vessels of the circle of willis using colour Doppler. Fourteen patients were assessed. The 14 fetuses were of normal growth and/or had normal umbilical arterial blood flow velocity waveforms as well as normal uterine blood flow. The mean term at the time of examination was 23.8 +/- 2.9 standard deviation with the extremes going from 28.5 standard deviation to 40.5. The examinations were carried out using colour Doppler (Acuson) machine by the abdominal route with a 3.5-5 MHz bi frequency sound. The vessels that were explored were the middle cerebral artery (CM), posterior cerebral artery (CP), the internal carotid artery (CI), the anterior cerebral artery (CA) in the region of the circle of Willis. CM and CA were able to be recorded in 100% of the cases, CP and CI in 93% of cases (13 out of 14 cases). The difference between he mean index (D/S, D = residual velocity in the diastole, S = maximum velocity in the systole) in each of these vessels was not statistically significant. In 3 out of 16 measurements (19%) the CP index was considered to be pathological while the index in the other vessels was normal, or when a different form of measurement was carried out in the region of CP, it was normal. This was also the case once for CA, but never for CM or CI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430916 TI - [Pregnancy after renal transplantation. 27 patients and review of the literature]. AB - We report the course and outcome of 30 pregnancies in 27 renal transplant patients between 1970 and 1988. Delay between transplantation and pregnancy was 7.3 +/- 4.8 years. There were 1 twin pregnancy and 3 successive pregnancies. Immunosuppressive regime was prednisone and azathioprine in 28 cases and cyclosporine in 2. Hypertension (33%), preterm delivery (74%) and premature rupture of the membranes (33%) were the main complication encountered. The cesarean section rate was 73%, mainly because of these complications. Twenty seven patients delivered of 31 healthy children. There was no congenital anomaly. Mean birth weight was 2.640 +/- 645 g. In utero growth retardation occurred in 7 cases (23%). Pregnancy after renal transplantation is of good prognosis for both the mother and child but the course of pregnancy can be complicated by hypertension, preterm birth and growth retardation. PMID- 1430917 TI - [Pregnancy after hepatic transplantation. 17 pregnancies]. AB - The number of orthotopic liver transplantations (OLT) is increasing and longterm survival is improving. More women recipients may choose to become pregnant. We report a one-center experience with the course and outcome of 17 pregnancies in 17 liver transplant out of 675 OLT since 1985. 10 women delivered of 10 healthy infants at 38 +/- 1.5 week's gestation. There was no preterm delivery and the mean birth weight was 2.990 +/- 370 g, birth weight was adequate for gestational age in any case. Four cesarean sections were performed for obstetrical indications. No congenital anomalies occurred in the children. Hypertension occurred in 2 out of twelve patients and appeared as the main complication to deal with. There was one case with graft function impairment at 37 weeks' gestation. One uncomplicated pregnancy is ongoing at 29 weeks' gestation. There were 4 spontaneous and 2 therapeutic abortions for impaired liver function. Pregnancy is successful in a large proportion of these patients but must be planned and managed as high-risk situations by an obstetrician and a specialist of the liver transplant. Pregnancy should be advised against in patients with poor liver function or active viral infection; a 12 months interval from OLT to pregnancy is since to be the minimal requirement. Post-transplant immunosuppressive therapy consisted of azathioprine, corticosteroids and ciclosporin A, and was maintained throughout pregnancy. Genetic counselling should be provided when the primary liver disease is inherited. This being said, as shown by the results of our study and those reported in the literature, pregnancy is not only feasible but also successful in a large proportion of OLT recipients. PMID- 1430918 TI - [Pregnancy in the diabetic woman. Incidence of malformations, of macrosomia, update on obstetrical management]. AB - Perinatal mortality for infants born to diabetic mothers has dropped in the years from the 1950's when it was 20% to less than 3% by the end of the 1980's. In spite of this considerable reduction which is due to careful observation and multidisciplinary management in this type of pregnancy, the congenital malformation rate is 4 times greater than with the general population (3%) and the rate of spontaneous abortions is double (13%). The caesarean section rate is 5 times higher (18%). In bringing out a retrospective study we have attempted to analyse the endocrinological and obstetrical features of the cases. PMID- 1430919 TI - [Major sickle cell anemia and pregnancy. Systematic prophylactic transfusions. 13 case reports]. AB - The seriousness of sickle cell disease together with pregnancy has led doctors to look for therapies which have yet scarcely shown their worth. Systematic blood transfusions in pregnancy did seem to improve the prognosis for both mother and fetus. Prophylactic transfusion has made it possible for us to carry thirteen pregnancies to term. There was no mortality either of fetus or mother while the morbidity either of fetus or mother while the morbidity was significantly cut down to new pathologies which were easily treated. The absence of any side effects from the transfusions encourages us to contribute this treatment working together with a highly competent blood transfusion bank. PMID- 1430920 TI - [Breech extraction of the second twin with or without version by internal maneuvers]. AB - A retrospective study was done to appraise the recent practice of breech extraction of the second twin (with or without internal version) in our unity. From January 1st, 1988 to April 30, 1991 23 patients with a twin gestation were delivered in our unity (0.5% of all deliveries). Nineteen patients (83%) were delivered vaginally. Each procedure was done by a resident under control of a senior obstetrician and in the presence of two midwives, a pediatrician, and an anesthesiologist. Ten patients having had a breech extraction (GE group) were studied, 13 patients were excluded for not having had a breech extraction. In the GE group the presentations were: 7 vertex/breech and 3 breech/breech. Mean Apgar scores of the second twin at 3 minutes were 8 in the GE group. These results suggest that breech extraction of the second twin is not a pernicious technique if done by trained operators with precise limits. These results need to be confirmed through a prospective randomized and comparative study. PMID- 1430921 TI - [Radical laparoscopic vaginal hysterectomy]. PMID- 1430922 TI - [Complications of laparoscopic surgery]. PMID- 1430923 TI - [Anaphylaxis after delivery: latex could be responsible]. PMID- 1430925 TI - Endoscopic carpal tunnel release. AB - We have performed 149 consecutive one-portal and 152 consecutive two-portal endoscopic carpal tunnel release operations. Average time to cessation of preoperative symptoms was 15 days in both the one-portal and two-portal groups. The average time of return to work was 16 days in the one-portal group and 17 days in the two-portal group. The complication rate in the one-portal group was 6%, and in the two-portal group it was 5%. In our opinion, the one-portal release technique is much more difficult and inherently more dangerous than the two portal technique, and we recommend the latter for endoscopic carpal tunnel release. PMID- 1430924 TI - Endoscopic carpal tunnel release: a cadaveric study. AB - Five surgeons performed endoscopic (Dyonics) carpal tunnel releases on 24 fresh cadaver wrists. In 50% of the specimens, transection of the transverse carpal ligament was incomplete. The average amount of incomplete release was 31% (range, 0% to 53%). Three types of incomplete release were noted: (1) release of Guyon's canal release--one, (2) incomplete distal ligament release--five, and (3) incomplete central or superficial release--six. Other technical errors were noted in nine of 24 specimens. There were no nerve lacerations. Endoscopic carpal tunnel release is either a technically demanding procedure, commonly results in incompletely released ligaments, or both. Proper training, followed by practice on several cadaver specimens before its clinical use, is recommended. PMID- 1430926 TI - Carpal arch alteration and related clinical status after endoscopic carpal tunnel release. AB - One hundred eight endoscopic carpal tunnel releases were performed by a modification of the technique described by Chow. Eighty-seven of the 108 cases were evaluated for quantitative postoperative widening of the transverse carpal arch. The average postoperative widening of the transverse carpal arch was 0.17 cm (7%), with a range of 0 to 0.5 cm. Seventy percent of the patients showed 0% to 10% widening, 26% showed 10% to 20% widening, and 4% showed more than 20% widening of the transverse carpal arch. Preliminary findings show that 3 weeks after endoscopic carpal tunnel release, pinch strength was at 102% and grip strength at 86% of preoperative values. Six weeks after surgery, pinch strength was 106% and grip strength was 121% of preoperative values. The complication rate in this series was 3%. The transverse dimension of the carpal arch generally widens after endoscopic carpal tunnel release but to a lesser degree than has been reported for open carpal tunnel release. The rate of improvement of pinch and grip strength after endoscopic release is faster than that reported in the literature after open release. PMID- 1430927 TI - Dynamic changes of the transverse carpal arch during flexion-extension of the wrist: effects of sectioning the transverse carpal ligament. AB - The width of the carpal arch, represented in this study by the distance between the tips of two Kirschner wires--one inserted into the trapezium and another into the hook of the hamate--was measured with precision calipers in 21 patients with carpal tunnel syndrome, both before and after sectioning of the transverse carpal ligament and in different wrist positions. With the ligament intact, most of the wrists showed a decrease in the distance in both flexion and extension. The distance increased an average of 11% after sectioning of the transverse carpal ligament. The dynamic behavior of the carpal arch, however, was not substantially modified by this procedure. PMID- 1430928 TI - Results of treatment of severe carpal tunnel syndrome. AB - A retrospective study was undertaken to determine the efficacy of carpal tunnel decompression in patients with advanced carpal tunnel syndrome. The criteria for inclusion in this study were unobtainable median sensory-evoked response and absent or prolonged median motor distal latency. Fifteen hands in 13 patients met these criteria. All patients had symptoms, including pain, weakness, or decreased sensation. Postoperative follow-up averaged 27 months. Symptomatic improvement was obtained in 14 of the 15 hands, and sensory-evoked response improved in 13 hands. Preoperative thenar atrophy was present in 10 of the 15 hands and was completely resolved in 2 of the 10 patients. These results indicate that carpal tunnel decompression is of benefit to patients with severe carpal tunnel syndrome. Long-standing symptoms, thenar atrophy, virtual anesthesia, and the absence of demonstrable sensory and motor-evoked responses are not contraindications to surgery. PMID- 1430929 TI - Fibroma of tendon sheath as a cause of carpal tunnel syndrome. PMID- 1430930 TI - An analysis of the flexor synovium in idiopathic carpal tunnel syndrome: report of 625 cases. AB - This study was undertaken to determine the presence or absence of tenosynovitis in persons with idiopathic carpal tunnel syndrome. Eight hundred thirty-five consecutive operations for carpal tunnel syndrome were retrospectively reviewed, and 625 cases of idiopathic carpal tunnel syndrome were identified. Of these 96% (601) had a synovial tissue histologic diagnosis of benign fibrous tissue without inflammation, 4% (23) showed chronic inflammation, and 0.2% (1) revealed evidence of acute inflammation. We believe that tenosynovitis is not a part of the pathophysiologic process in chronic idiopathic carpal tunnel syndrome. Further histologic analysis of the flexor synovium for pathologic changes other than inflammation is needed. PMID- 1430931 TI - Acute gout after carpal tunnel release. AB - A carpal tunnel release was performed on three patients with known gout of the lower extremity but not of the upper extremity. Each patient had a postoperative inflammatory reaction in a treated hand, and there was some suspicion of an infection in two patients. However, the inflammatory reaction resolved only when treated with a combination of anti-inflammatory and anti-gout medication. PMID- 1430932 TI - Variations in digital nerve anatomy. AB - One hundred digital nerves from 10 cadaver hands were dissected, and branching patterns were analyzed. Contrary to the traditional belief that the digital nerve predictably trifurcates at the distal interphalangeal crease, much variation exists. Terminal branching occurred distal to the crease in 60% of the thumb digital nerves and in 78% of the digital nerves supplying the other four digits. The number of terminal branches also varied from two to seven in the thumb and from two to five in the other four digits. No significant differences were seen in branching patterns between digits or between radial and ulnar sides. These findings are clinically relevant to the surgeon who is contemplating digital nerve repair. PMID- 1430933 TI - The superficial branch of the radial nerve: an anatomic study with surgical implications. AB - Twenty fresh cadaver extremities were dissected to delineate and quantify the course of the superficial branch of the radial nerve. This branch bifurcated from the radial nerve at the level of the lateral humeral epicondyle in eight specimens, and in all specimens the bifurcation was no more than 2.1 cm from the lateral epicondyle. It continued distally, deep to the brachioradialis and became subcutaneous a mean of 9.0 cm proximal to the radial styloid, traversing between the tendons of the brachioradialis and extensor carpi radialis longus. The superficial branch of the radial nerve branched a mean of 5.1 cm proximal to the radial styloid. Distally, at the level of the extensor retinaculum, the closest branches to the center of the first dorsal compartment and to Lister's tubercle were mean distances of 0.4 and 1.6 cm, respectively. In the hand, the superficial branch of the radial nerve most commonly supplied branches to the thumb, the index finger, and the dorsoradial aspect of the long finger. Knowledge of the course of the superficial branch of the radial nerve will help prevent injury during operative procedures on the radial side of the hand, wrist, and forearm and will aid in its localization in treatment of traumatic injuries or performance of nerve blocks in its distribution. PMID- 1430934 TI - A socioeconomic analysis of digital replantations resulting from home use of power tools. AB - Forty-seven digits in 21 patients who sustained partial or complete amputations from the home use of power tools were replanted or revascularized during a 1-year period. This represented 69% of the microvascular surgery performed for hand injuries during that year. The cost of repairing an average of 2.4 digits was $7000 (surgeon's fee) plus $697 per hour (operating room fee), as per fiscal year 1987. Postoperative hospitalization averaged 15 days at a cost of $15,679. Hand rehabilitation averaged 8 months at a cost of $3348. Fifty-four percent of the patients had no insurance. Fourteen of 21 patients (67%) required at least one additional procedure. Two patients had to make a career change after the injury. The majority of patients with digital replantations were dissatisfied with the emotional costs and the number of subsequent operations. Lack of patient and family awareness of the length of the rehabilitative period was particularly evident. PMID- 1430935 TI - Maintenance of patency after vascular trauma by topical irrigation with a peptide homologous to the carboxy-terminus of the fibrinogen gamma chain. AB - Synthetic peptides with amino acid sequences homologous to the carboxy-terminal sequence of the gamma chain of human fibrinogen were evaluated for their capacity to inhibit thrombus development. A 21-residue peptide effectively inhibited surface-mediated fibrin clot propagation in vitro. Since this effect was localized to the surface, we proceeded with in vivo evaluation, using site specific topical application only. In a rat model of arterial trauma and microvascular repair, topical application of the 21-residue peptide significantly reduced the rate of thrombosis to 17%, as compared with a control rate of 83%; in comparison, a 12-residue homologue reduced the thrombosis rate only modestly to 61%, which was not significant compared with the control rate. These results indicate the feasibility of antithrombotic therapy with topically applied agents, an approach that may obviate the use of systemic anticoagulation in extremity replantation surgery. PMID- 1430936 TI - Hemangiopericytoma of the hand: a literature review and case study. AB - We present a case of hemangiopericytoma of the hand. We also attempt to differentiate hemangiopericytoma from glomus tumor with a summary of the history and a comprehensive review of the literature demonstrating the malignant character of the neoplasm, and we offer some guidelines for treatment. PMID- 1430937 TI - Pellet embolus of the distal ulnar artery. PMID- 1430938 TI - Solitary osteochondroma limiting flexion of the proximal interphalangeal joint in an infant: a case report. PMID- 1430939 TI - Long-term functional results after pollicization for the congenitally deficient thumb. AB - This study objectively investigated the functional results of 28 index finger pollicizations for correction of congenital deficiency of the thumb. The results indicate that the average total active range of motion at the pollicized digit was 98 degrees, or approximately 50% that of a normal thumb. The average grip strength was 21% of standard values; lateral, tripod, and tip pinch strength values ranged from 22% to 26% of standard values. The pollicized digit was used in the manner of a normal thumb or in modified fashion in 84% of 14 defined activities, with increased use for handling large objects (92%) and less use for small objects (77%). The time required to perform activities averaged 22% longer than the standard for a normal hand. Patients with a radial club hand, a five finger hand, or a mirror hand on the affected extremity had significantly poorer results; however, patients without one of these associated conditions had near normal use of the pollicized digit, except for reduced strength. These results were not influenced by the age of the patient at the time of operation. This information should be helpful in counseling parents with children who are candidates for pollicization as to what functional results they might anticipate. PMID- 1430940 TI - Insecticide injection injuries to both hands: a case report. PMID- 1430941 TI - Melorheostosis of the hand: a report of two cases. AB - Two cases of melorheostosis of the hand are reported. Histopathologic examination confirmed the characteristic x-ray findings and excluded other skeletal dysplasias, such as osteopoikilosis and osteopathia striata. PMID- 1430942 TI - Osteochondritis dissecans of the head of the second metacarpal bone. PMID- 1430943 TI - A solitary osteochondroma of the capitate bone: a case report. PMID- 1430944 TI - Bilateral intraosseous ganglia of the lunate: a case report. AB - A rare case of bilateral intraosseous ganglia of the lunate is reported. The patient had had 7 months of pain in both wrists and a cystic lesion in both lunates. Curettage and bone grafting resulted in complete relief of pain. PMID- 1430945 TI - Avascular necrosis of the hamate: a case report with reference to the hamate blood supply. AB - Avascular necrosis of the hamate bone has not previously been reported. In this case the proximal fragment of the fractured hamate underwent avascular necrosis and prolonged healing. In an attempt to explain this sequela, angiography of the cadaver carpus followed by dissection of intact wrists and a study of enzyme cleaned hamates showed that their wedge-shaped proximal segments were mostly enveloped by a distal extension of the midcarpal joint cavity and thus totally dependent on intraosseous nutrition. Consequently, the segment is at risk when a fracture line transects the body proximal to the base of the wedge. Clinically, this condition resulted in persistent discomfort and limitations of motion. A postinjury bone scan of the wrist indicated avascular changes in the proximal third of the hamate, and a delayed union was followed by later revascularization and a more normal scan image. PMID- 1430946 TI - Avascular necrosis of the capitate: a case report. PMID- 1430947 TI - Metastatic basal cell carcinoma of the upper extremity. PMID- 1430948 TI - Parosteal lipoma of the proximal radius: a report of five cases. AB - Parosteal lipoma of the proximal radius is a benign, slow-growing tumor. It may cause compression of either the posterior interosseous or the superficial branch of the radial nerve. Surgical excision usually leads to complete recovery. Five cases of parosteal lipoma of the proximal radius are presented. X-ray films demonstrated a radiolucent mass in contact with the radius. Two patients had signs of posterior interosseous nerve compression, and two showed signs of superficial radial nerve compression. In one case the lipoma surrounded an exostosis arising from the proximal radius. The tumors were excised in four patients. The three patients with neurologic involvement recovered fully. One patient refused surgery, and posterior interosseous nerve paralysis developed. PMID- 1430949 TI - Efficacy of immobilization following aspiration of carpal and digital ganglions. AB - In a prospective study 69 carpal and digital ganglions were aspirated, multiply punctured, and digitally ruptured. Fifty percent of the wrists and digits were immobilized for 3 weeks and 50% were mobilized early. Follow-up was 1 year. Immobilization in our study did not significantly improve the results of treatment. During the course of the study, 51% of all ganglions did not recur. The outcome was successful in 52% of the wrists and digits that were immobilized and in 50% of those that were not. Forty-six percent of the dorsal carpal ganglions did not recur. Treatment was successful in 48% of dorsal carpal ganglions in which the wrists were immobilized and in 45% of those that were not. Similar percentages were found for palmar and digital ganglions. From our results, we conclude that immobilization does not significantly improve the successful treatment of ganglions over perforation and aspiration alone. PMID- 1430950 TI - The effect of elbow flexion and time of assessment on the measurement of grip strength in rheumatoid arthritis. AB - Grip strength is one of the traditional outcome measures commonly used in rheumatoid arthritis trials. This study evaluated the degree of morning variation and the effect of elbow flexion in the assessment of grip strength in patients with rheumatoid arthritis. Grip strength was measured in 37 patients (1987 American Rheumatism Association criteria) at 8, 10, and 12 AM with a sphygmomanometer cuff folded on itself, taped permanently, and inflated to 20 mm Hg, with the elbow flexed at 90 degrees. At 10 AM grip strength was also measured with the elbow flexed at 30 and 130 degrees. Mean values for grip strength at 8, 10, and 12 AM were, respectively, 69, 79, and 83 mm Hg. Mean grip strength values with the elbow flexed at 30, 90, and 130 degrees were, respectively, 78, 79, and 75 mm Hg. There was a statistically significant correlation between grip strength and morning stiffness, grip strength and hand function, and grip strength and number of active joints. In rheumatoid arthritis trials, grip strength should be assessed at the same time of the day. Elbow flexion does not play a role in grip strength measurement. PMID- 1430951 TI - Limited arthrodesis for the rheumatoid wrist. AB - Limited arthrodesis of the proximal carpal row to the radius, synovectomy of the extensor tendons and the wrist joint, and a Darrach procedure were carried out in 25 unstable painful rheumatoid wrists that had ulnar shift and/or palmar subluxation of the carpus. The average follow-up period after the operation was 3 years. Satisfactory results were obtained with relief of pain, improved forearm rotation, and increased grip strength. The average degree of extension and flexion was reduced, respectively, 70% and 54% at follow-up compared with the preoperative range. Postoperative x-ray films showed deterioration in the lunocapitate joint in 12 wrists; however, the wrists remained stable and painless. PMID- 1430952 TI - Rheumatoid wrists treated with synovectomy of the extensor tendons and the wrist joint combined with a Darrach procedure. AB - Forty-three rheumatoid wrists in 43 patients with bilateral wrist involvement were treated with synovectomy of the extensor tendons and wrist joint combined with a Darrach procedure in the period from 1966 to 1986. Clinical and radiologic assessment of the wrists was carried out after an average follow-up period of 11 years, with comparison of the treated and the opposite untreated wrists. The authors confirmed what others have concluded regarding the operation: pain was generally decreased, forearm rotation increased, and wrist extension and palmar flexion changed little. Radiologically, carpal collapse and palmar carpal subluxation progressed nearly parallel to the opposite wrists, but ulnar carpal shift was much greater in the surgically treated wrists. Therefore it is suggested that some measure to prevent ulnar carpal shift, such as Clayton's tendon transfer or radiolunate arthrodesis, should be included in this operation. PMID- 1430953 TI - Biomechanical characteristics of extensor tendon suture techniques. AB - Despite their ease of exposure, extensor tendons can be difficult to handle and suture well. Compared with flexor repair, little is known about the various factors that affect the suturing of extensor tendons. The present study was designed to investigate several biomechanical parameters involved in extensor repair. All techniques studied shortened the tendon considerably and produced significant losses of flexion at the metacarpophalangeal and proximal interphalangeal joints. In addition, repairs achieved with all suture techniques were considerably weaker than those achieved when comparable techniques were used on flexor tendons. However, the Kleinert modification of the Bunnell technique provided the strongest sutures in extensor tendons, produced no gapping, caused the least worrisome loss of metacarpophalangeal and proximal interphalangeal flexion, and best approximated the results found in an idealized tendon shortening model. PMID- 1430954 TI - Tendon graft donor sites. AB - Each of 480 extremities from 120 cadavers was dissected. Particular attention was given to potential donors for tendon grafts. Both the palmaris longus and the extensor digiti minimi had an average length of 16 cm and an average width of 3 mm. The extensor indicis tendon averaged 13 cm in length and 3 mm in width. The plantaris and second toe extensors averaged 35 cm in length and 2 to 2.5 mm in width. None of these measurements correlated well with age, sex, or hand or foot size. There was, however, a high correlation between right- and left-side measurements in each specimen, in spite of some degree of anatomic variation for all the tendons studied. The palmaris longus was missing in 25% of the upper extremities, and the plantaris in 19% of the lower extremities dissected. PMID- 1430955 TI - The correlation between controlled range of motion with dynamic traction and results after flexor tendon repair in zone II. AB - This prospective study investigated the extent to which the range of interphalangeal joint motion during early mobilization with dynamic traction influences the results after flexor tendon repair in zone II. The controlled interphalangeal joint range of motion within the splint was measured 3 weeks postoperatively in 51 digits (48 patients). The active range of motion was measured 4 weeks, 6 weeks, and 1 year postoperatively. Linear regression analysis showed that controlled interphalangeal range of motion had a significant effect on both early and late results. The results provide, for the first time, firm clinical evidence to support the rationale for early mobilization programs designed to maximize controlled interphalangeal joint range of motion. PMID- 1430956 TI - Distal interphalangeal joint arthrodesis: an analysis of complications. AB - One hundred thirty-nine patients underwent 181 arthrodeses of finger distal interphalangeal joints (144) and/or thumb interphalangeal joints (37). Techniques included (1) crossed Kirschner pins (111 joints), (2) interfragmentary wire and longitudinal Kirschner pin (43 joints), and (3) Herbert screw (27 joints). Each technique had a similar nonunion rate. There were 21 nonunions: 13 were pain free, 6 were successfully fused on the second attempt, 1 was painful (but the patient refused further surgery), and 1 was amputated. Inadequate bone stock, inadequate bone resection, premature pin removal, and infection appear to complicate the attainment of bony union. Twenty percent of the fusions had major complications (nonunion, malunion, deep infection, and osteomyelitis). Minor complications (dorsal skin necrosis, cold intolerance, proximal interphalangeal joint stiffness, paresthesias, superficial wound infection, and prominent hardware) occurred in 16% of the joints fused. PMID- 1430957 TI - Irreducible open dislocation of the metacarpophalangeal joint of the small finger. PMID- 1430958 TI - Intra-articular corticosteroid reduces joint stiffness after an experimental periarticular fracture. AB - Early care after surgery or trauma to the extremities often includes a period of immobilization. The resultant joint stiffness may require extensive rehabilitation and may permanently limit function of the limb. Posttraumatic joint stiffness is particularly vexing in the small joints. In an experimental model, we tested the effects of intra-articular corticosteroid injections on stiffness in a joint at risk of posttraumatic joint stiffness. Triamcinolone was injected into ankle joints of rabbits after distal tibial fractures. Three weeks after injury, joint stiffness increased 34% in ankles injected with the steroid. Stiffness in ankles injected with saline solution and in ankles treated with no injection increased 133% and 224%, respectively. Limb swelling and tibial torsional strength to failure were not significantly affected by either of the treatments. PMID- 1430959 TI - Severe contractures of the proximal interphalangeal joint in Dupuytren's disease: results of a prospective trial of operative correction and dynamic extension splinting. AB - In a prospective study, 23 proximal interphalangeal joints that were severely contracted (> or = 45 degrees) as a result of Dupuytren's disease underwent operative correction and 6 months of dynamic extension splinting. Proximal interphalangeal joint extension was measured preoperatively and postoperatively at 3-month intervals for 1 year and at 6-month intervals thereafter. Mean follow up was 2 years (minimum, 1 year). Overall, at 2 years, 44% improvement in proximal interphalangeal joint extension was noted. Mean improvement of 59% in proximal interphalangeal joint extension was noted in patients who complied with the postoperative dynamic extension splinting program. Patients who were noncomplaint demonstrated a 25% improvement in proximal interphalangeal joint extension. The difference in values between patients who were compliant and those who were not was statistically significant. Other factors--severity of contracture, digit involved, and the necessity for capsular release--were not significantly related to outcome. This study suggests that soft tissue responds to continuous dynamic extension stresses and can be remodeled over time. PMID- 1430961 TI - A technique for planning skin flaps in the hand. PMID- 1430960 TI - A safe, reliable method of carpal tunnel injection. AB - The injection of steroid preparations into the carpal canal is a recognized practice in the management of carpal tunnel syndrome. This procedure is associated with a risk of temporary or permanent damage to the median nerve. We present a new method of carpal tunnel injection based on anatomic dissections. We have used this technique successfully for more than 10 years, and there have been no cases of median nerve injury. PMID- 1430962 TI - Occupational disorders--the disease of the 1990s. PMID- 1430963 TI - Thoughts on the technique of carpal tunnel release. PMID- 1430964 TI - Endoscopic release of the carpal tunnel: a randomized prospective multicenter study. AB - A 10-center randomized prospective multicenter study of endoscopic release of the carpal tunnel was carried out. Surgery was performed with a new device for transecting the transverse carpal ligament while control hands were treated with conventional open surgery. There were 122 patients in the study; 25 had carpal tunnel surgery on both hands and 97 had surgery on one hand. Of the surgical procedures, 65 were in the control group and 82 were in the device group. The endoscopic device was coupled to a fiberoptic light and a video camera. A trigger activated blade was used to incise the transverse carpal ligament. After surgery, the best predictors of return to work and to activities of daily living were strength and tenderness variables. For patients in the device group with one affected hand, the median time for return to work was 21 1/2 days less than that for the control group. Two patients treated with the endoscopic device required reoperation by open surgical decompression; only one of these had incomplete release with the device. Two patients in the device group experienced transient ulnar neurapraxia. PMID- 1430965 TI - Endoscopic carpal tunnel release: an anatomic study of the two-incision method in human cadavers. AB - To determine the relationship of neurovascular structures to the sites of portal placement and transverse carpal ligament division during two-portal endoscopic carpal tunnel release, a study of 20 fresh cadaver specimens was carried out. Open dissection of the carpal tunnel after endoscopic surgery showed complete ligamentous release in 18 hands (90%). In 10 specimens, the procedure was performed as described by Chow. There was one partial transection of the superficial palmar arch (5%), and five specimens (50%) had complete divisions of the superficial palmar fascia with considerable pressure placed on the ulnar nerve at the wrist. A modified technique was used in 10 specimens in which the proximal incision was made in a more distal location and a distally based ligamentous flap was created. The superficial palmar arch and the distal edge of the transverse carpal ligament were visualized directly before passage of the trocar. No complications were noted with this method. PMID- 1430966 TI - Perfusion studies in cholera: methods and procedures. AB - This paper reviews the characteristics of perfusion techniques in the study of intestinal functions by specifically examining the methods and procedures of perfusion in patients with diarrhoea due to infection with V. cholerae 01. Because of abundant jejunal secretion of water and electrolytes in cholera, perfusion studies require special approaches with regard to patient preparation, use of tubing material, selection of markers, and rate of perfusion. A discussion on specific problems involved in marker perfusion techniques in cholera and on the interpretation of the results is followed by practical recommendations. PMID- 1430967 TI - Regulation of the SLT-1A toxin operon by a ferric uptake regulatory protein in toxinogenic strains of Shigella dysenteriae type 1. AB - The regulation of Shiga toxin expression in a clinical isolate of S. dysenteriae 1 by the Fe-Fur (Iron-ferric uptake regulatory protein) repressor complex was investigated. The presence of an endogenous Fur repressor protein capable of binding to either a Fur binding consensus sequence or the regulatory region of SLT-1A was determined in toxinogenic strains of S. dysenteriae. Plasmid constructs bearing Fur binding sites fused to readily assayable reporter genes were used. Plasmid pSC27.1 contains a 21 bp synthetic oligonucleotide Fur protein binding consensus sequence located upstream to the gene for beta-galactosidase. Plasmid pSC105 contains the regulatory sequences of Shiga-like toxin-1A located upstream to the gene for alkaline phosphatase. In an analogous fashion to Shiga toxin regulation in S. dysenteriae 1, transformants bearing either pSC27.1 or pSC105 plasmid DNA were repressed in gene product expression when grown in minimal medium supplemented with iron. Conversely, transformants were de repressed when grown under iron limiting conditions. These data suggest the presence of Fe-Fur mediated regulation of toxinogenesis in clinical isolates of S. dysenteriae. PMID- 1430968 TI - Efficacy of norfloxacin for shigellosis: a double-blind randomised clinical trial. AB - In a double-blind, randomised, clinical trial on 122 adults with acute Shigella dysentery, 60 patients were treated with norfloxacin and 62 with nalidixic acid. Of these, 32 patients in the norfloxacin group and 28 patients in the nalidixic acid group had Shigella in their stool. Patients of the two treatment groups were clinically comparable on admission. No significant differences in clinical responses were observed in the two groups among the Shigella-positive cases, Shigella-negative cases and among the total cases. All isolates of Shigella were susceptible to norfloxacin, whereas 13.8% of the strains were resistant to nalidixic acid. PMID- 1430969 TI - Detection of specific anti-Giardia antibodies in the serodiagnosis of symptomatic giardiasis. AB - The roles of circulating anti-Giardia IgM and IgG antibodies were assayed by the Enzyme linked immunosorbent assay (ELISA) using axenic Giardia lamblia whole trophozoites as antigen for routine serodiagnosis of Giardia infection. Detection of anti-Giardia IgM antibody was found to be useful in the early detection of symptomatic giardiasis, whereas IgG detection was not, since the latter could not discriminate between present infection and previous exposure. A mean optical density (OD) +/- 2 standard deviation (SD) value of 0.088 at 1:100 serum dilution was found optimal for the detection of anti-Giardia IgM antibodies as it completely separated out the acute Giardia cases from the Giardia-free controls. The same sera did not reveal any marked differences when tested for anti-Giardia IgG antibodies. Detection of IgM antibodies correlated with high sensitivity and specificity (96%) in an evaluation of a large number of sera collected from Giardia cases and controls. PMID- 1430970 TI - Antimicrobial susceptibility of Clostridium difficile strains isolated from hospitalised patients with acute diarrhoea. AB - The susceptibility of 43 Clostridium difficile strains to twelve antimicrobials was tested in vitro by agar dilution. All of the 43 strains were inhibited by low concentrations of metronidazole, penicillin G, tetracycline and ampicillin. The strains were highly resistant to gentamycin, trimethoprim, sulphamethoxazole, nalidixic acid, cycloserine, cefotaxime and uniformly sensitive to metronidazole and penicillin G whereas the activity of other antimicrobials are variable. PMID- 1430971 TI - Failure to isolate Yersinia enterocolitica from patients with diarrhoea in Singapore. AB - To determine the presence of Yersinia enterocolitica in Singapore, an attempt was made to isolate this organism from the stool samples of 6,619 patients with diarrhoea. No Y. enterocolitica was detected. The results suggest that Y. enterocolitica is not an important bacterial pathogen causing diarrhoeal disease in this region. PMID- 1430972 TI - Acute secretory travellers' diarrhoea caused by Vibrio cholerae non-01 which does not produce cholera-like or heat-stable enterotoxins. AB - An Australian tourist suffering from severe acute watery diarrhoea and dehydration due to Vibrio cholerae non-01 was studied. The V. cholerae strain isolated from the patient belonged to serovar 05. The organism did not produce any of the conventional enterotoxins including cholera-toxin (CT) or heat-stable toxins (NAG-ST) that are known to be associated with intestinal secretion. This report suggests that toxin(s) other than CT-like or NAG-ST may be involved in the pathogenesis of diarrhoea by some V. cholerae non-01 strains. PMID- 1430973 TI - A 1-year old girl with severe malnutrition, bloody-mucoid diarrhoea and fever. PMID- 1430974 TI - Bibliography on diarrhoeal diseases. PMID- 1430975 TI - Peer review organization payment denials: comparative analysis of emergency department and non-emergency-department admissions. AB - The Health Care Financing Administration has contracted with regional peer review organizations to review Medicare admissions and to deny payment for hospital admissions that fail to meet peer review organization criteria. The purpose of this study was to compare emergency department admissions with non-emergency department admissions with respect to rates of peer review organization denial and the reasons for those denials. All hospital Medicare admissions between January 1984 and April 1987 were retrospectively reviewed. Patients were excluded if they received peer review organization pre-authorization prior to admission. The rest were classified by 1) source of admission (emergency department or non emergency department), 2) peer review organization decision, 3) reason for peer review organization denial, 4) whether the denial was appealed, 5) the results of appeal. Chi-square or Fisher's Exact Test analysis was performed, and P less than 0.05 was considered to be significant. During the 40-month study period, there were 19,847 emergency department Medicare admissions and 19,752 non-emergency department Medicare admissions. Of the non-emergency-department admissions, 7887 received pre-authorization. None of the emergency department admissions received pre-authorization. Of the 19,847 emergency department admissions, 433 (2.23%) were denied. Of these denials, 269 (60.7%) were appealed by the hospital; 136 (50.5%) successfully. Of the 11,865 non-emergency department, non-pre-authorized admissions, 333 (2.81%) were denied. Of these denials, 174 (52.2%) were appealed, 76 (43.6%) successfully. Overall, emergency department admissions were significantly less likely to receive peer review organization denial than non emergency-department, non-pre-authorized admissions (P less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1430976 TI - Respiratory rates in pediatric emergency patients. AB - Respiratory rates are routinely measured in pediatric emergency patients. The normal range has not been established, and commonly reported ranges seem lower than those encountered in clinical practice. This prospective study selected subjects from pediatric patients presenting for care to a suburban emergency department. All respiratory rates were measured for one full minute. Patients with complaints related to the cardiopulmonary system or with an elevated temperature were excluded. A total of 434 patients were entered into the study over a 3-month period of time. Ages ranged from 2 weeks to 18 years. Respiratory rates ranged from a high of 65 breaths/min in a 4-month-old to a low of 12 breaths/min in a 14-year-old. Respiratory rate was inversely related to age, and there was a broad range in every age group. Our study shows that a normal respiratory rate is inversely related to age and is higher than noted in previously published studies. The wide range of "normal" pediatric respiratory rates makes identification of "abnormal" more difficult. PMID- 1430977 TI - Pain comparison of unbuffered versus buffered lidocaine in local wound infiltration. AB - The purpose of this study was to compare the pain of infiltration between unbuffered lidocaine and buffered lidocaine in a traumatic laceration. Solutions of unbuffered 1% lidocaine and buffered 1% lidocaine were randomly assigned to Site I or Site II of a single laceration for each subject, with the patient serving as self-control. Pain scores were recorded for each site, and an anesthetic preference was determined for each patient. It was found that buffered lidocaine had a preference ratio of 3.0 over unbuffered lidocaine (95% confidence interval, 1.86 to 4.84; P less than 0.0001). It was also found that Site I was preferred more often than Site II regardless of which medication was used. The conclusion is that buffered lidocaine is preferred over unbuffered lidocaine and that the order of injection is an important factor in trials that involve multiple sequential injections in the same patient. PMID- 1430978 TI - Insertion forces and risk of complications during cricothyroid cannulation. AB - Our purpose was to determine the forces required to insert several different styles of cricothyroid cannulas and to relate the magnitude of these forces and cannula design features to the incidence of complications during insertion. Tests were done on unembalmed cadavers and anesthetized dogs. Samples of 4 different commercial cricothyroid cannulas were tested. Each cannula type was tested in 5 different cadavers and 10 different dogs. A lubricant was applied to the cannulas in half of the dogs tested. Major findings are 1) there is a linear correlation between insertion force and device diameter, 2) higher puncture force is associated with a greater incidence of complications, 3) posterior wall penetration occurs more frequently with a curved penetrating device, 4) using small pilot needles to guide insertion of large cannulas minimizes complications, and 5) lubricant is less effective for cannulas having abrupt diameter changes. These findings provide guidelines for design of safer cricothyroid cannulas. PMID- 1430979 TI - Accidental hypothermia with cardiac arrest: recovery following rewarming by cardiopulmonary bypass. AB - A 22-year-old man eventually had a good neurologic recovery following prolonged coma after extracorporeal rewarming from profound hypothermia (24 degrees C) due to exposure. The patient was in full arrest for 60 minutes prior to institution of cardiopulmonary bypass (CPB). Total bypass time was 50 minutes. Cardiopulmonary bypass is the current rewarming method of choice for severe hypothermia associated with a persistent nonperfusing cardiac rhythm. CPB provides the most rapid core rewarming with the additional benefit of circulatory support during the period of cardiac instability. PMID- 1430980 TI - Xiphodynia: a report of three cases. AB - Xiphodynia is an uncommon musculoskeletal disorder that mimics a number of common abdominal and thoracic diseases. We report three cases of xiphodynia. The diagnosis is suggested when a given patient's chest or abdominal discomfort is completely or almost completely reproduced with light pressure on the xiphoid process. Local injection with an anesthetic-steroid combination is frequently curative. No more than 5 to 7 mL of solution should be injected, and results are variable when several trigger points are found on the anterior chest wall. Tack hammer deformity of the xiphoid, another cause of xiphoid pain, has been successfully treated with surgical excision. PMID- 1430982 TI - The sepsis workup for the febrile child. AB - The sick infant or toddler who presents with a high fever or suspected sepsis must have all possible sources for bacterial infection excluded by clinical evaluation or laboratory studies as quickly and safely as possible. The process is frightening and often painful for the child. The process can be difficult for the physician because of the smallness of anatomic structures in children and the infrequent performance of pediatric procedures by many emergency physicians. This article uses a case report to illustrate features of the sepsis workup. Methods and sites that have been used with the most frequent success are described and alternatives and pitfalls are listed. PMID- 1430981 TI - Wooden transnasal intracranial penetration: an unusual presentation. AB - A 2 1/2-year-old child presented to the emergency department with a wooden stick lodged firmly in her right nares. No nasal discharge or neurological abnormalities were noted at presentation. After plain radiographs failed to demonstrate any evidence of a foreign body, computed tomography (CT scan) was obtained that revealed a hypodense region in the right frontal lobe corresponding to the projected tract of the branch. The patient underwent a right frontal craniotomy with debridement of her contused right frontal lobe. She was discharged 8 days postoperatively without evidence of neurologic sequelae. This case illustrates an unusual presentation of intracranial penetration, with only six similar cases found in the literature. It also highlights the need for the emergency physician to be concerned about intracranial penetration when treating intranasal foreign bodies, particularly those of the nonmetallic type. The literature is reviewed regarding transnasal intracranial penetration by wooden foreign bodies. PMID- 1430983 TI - The diagnosis of acute myocardial infarction in the emergency department; Part 1. AB - Despite major advances in treatment, the accurate diagnosis of acute myocardial infarction (AMI) in the emergency department (ED) remains a difficult clinical problem and is still mainly based on the history and interpretation of the electrocardiogram. Although the physician's clinical impression is a highly sensitive indicator for AMI, at least 4% of patients presenting to the ED with AMI may be mistakenly sent home. Although chest pain is the most common chief complaint, the clinical presentation can be extremely variable, particularly in the elderly. Complaints of sharp chest pain or chest wall tenderness should not be relied upon to exclude AMI. Radiation of chest pain is an important symptom. With careful analysis, the electrocardiogram may yield a higher diagnostic sensitivity than is commonly accepted. PMID- 1430984 TI - A disposable emergency wound treatment kit. AB - Biomechanical studies in our laboratory have provided a scientific basis for selecting surgical gloves and instruments, drugs, and dressings for traumatic wound treatment. This armamentarium has been incorporated into a disposable emergency wound treatment kit for use in the emergency department. Its upper tray is for wound cleansing, while its lower tray is used for wound closure. A clinical evaluation of the kit by emergency physicians was very favorable because it saved time, eliminating the need to search for and assemble the gloves, instruments, drugs, and dressings for wound treatment. PMID- 1430985 TI - Technical considerations in manual and instrument tying techniques. AB - The purpose of this study was to relate the two-hand (manual) and instrument tie techniques with the ultimate security of granny and square knots constructed in multifilament and monofilament nylon sutures. Instrument-tie technique constructed secure granny and square knots, which failed by breakage rather than slippage. Similarly, two-hand (manual) tie techniques constructed square knots, which achieved knot security, failing only by breakage. In contrast, knot security was not reliably achieved with granny knots constructed by the two-hand (manual) tie techniques, with the knots frequently failing by slippage. PMID- 1430986 TI - LSD overdose in an eight-month-old boy. PMID- 1430987 TI - A perspective on emergency medicine in the developing world. AB - The author spent 6 months as director of a major university hospital accident and emergency department in Kuala Lumpur, Malaysia. A brief summary of this experience is provided, followed by a series of recommendations based on the experience that may provide some guidance in future efforts to establish emergency medicine in developing areas of the world. PMID- 1430988 TI - The emperor's new airway. PMID- 1430989 TI - Blood ethanol clearance rates. PMID- 1430990 TI - The English system. PMID- 1430991 TI - The reversal of the ischemic effects of epinephrine on a finger with local injections of phentolamine. PMID- 1430992 TI - Review of medical negligence cases: an essential part of residency programs. AB - Residency programs routinely review cases involving "morbidity and mortality." It would be a valuable experience to similarly review medical malpractice cases and the associated testimony by medical experts. When available, the cases reviewed in residency programs would be those in which faculty members at the same institution had testified. The faculty member in such cases would be intimately familiar with the case and able to share the knowledge necessary to take part in the legal process. This case review process would expose residents to the legal realities of medical practice, provide a forum for peer review of legal testimony by experts, and show residents how to participate in the legal system should the need arise. PMID- 1430993 TI - Objectives to direct the training of emergency medicine residents on off-service rotations; radiologic imaging 1: Plain films. AB - Interpretation of radiologic images is an essential skill for the emergency physician. This is the first of two sets of objectives for an off-service rotation in radiology. It covers the interpretation of plain films. The second series will address commonly used, but more sophisticated, imaging modalities including the use of contrast materials, ultrasound, nuclear medicine, computed tomography, and magnetic resonance imaging. This set of objectives may be used to guide a one-month radiology rotation or serve as part of a teaching program integrated with didactic training and emergency department experience. PMID- 1430994 TI - Emergency department discharges against medical advice. AB - A retrospective chart review was performed on 52 consecutive discharges against medical advice (AMA) from an emergency department. The study's objective was to assess documentation of the medical record as well as the patients' perceptions of their experience. Sixty-seven percent of the charts reflected the competence of the patient. The physicians documented that the patients understood their diagnosis (36%), proposed treatment (44%), alternative therapy (2%), and the clinical consequences of refusal (57%). The discharge instructions included a referral to a physician 62% of the time. A post-visit survey contacting 46% of the group revealed that 82% of these respondents left because they didn't agree with the physician's management plan, although 70% of the patients were either "very satisfied" or "satisfied" with their interaction with the physician. These results suggest that more attention and better documentation needs to be directed to the patient who is leaving the emergency department against medical advice. PMID- 1430996 TI - Tuberculin skin testing of hospital employees during an outbreak of multidrug resistant tuberculosis in human immunodeficiency virus (HIV)-infected patients. PMID- 1430995 TI - A rose by any other name. PMID- 1430997 TI - Reduction of C difficile-associated diarrhea. PMID- 1430998 TI - Nosocomial pneumonia. PMID- 1430999 TI - A study of the etiologies and treatment of nosocomial pneumonia in a community based teaching hospital. AB - OBJECTIVE: To compare the frequency of the pathogens of nosocomial pneumonia in a community-based teaching hospital to the frequencies previously published, and to evaluate recommendations for the therapy of nosocomial pneumonia in this setting. DESIGN: Retrospective review of prospectively acquired data accrued during 9 randomized single-blinded and 4 single-agent investigational antibiotic studies for the therapy of pneumonia in hospitalized patients between 1981 and 1989. SETTING: The study was performed at a university affiliated, community-based teaching Department of Veterans Affairs Medical Center. PATIENTS: Patients were hospitalized on the acute medical/surgical and intermediate medicine wards. Informed consent was obtained prior to enrolling patients into the respective antimicrobial studies. Pneumonia was documented radiographically and clinically for each patient. RESULTS: Two hundred thirty-one episodes of nosocomial pneumonia were treated. Overall, 51% of pneumonias were caused by Streptococcus pneumoniae or Hemophilus influenzae with or without other organisms that were not gram-negative bacilli. Gram-negative bacilli, with or without other organisms, accounted for only 26% of all nosocomial pneumonias. Overall, monotherapy with a cephalosporin (usually a broad-spectrum agent) was equally efficacious compared with combination therapy (87% versus 81%, respectively). Cure rates for nosocomial pneumonias from gram-negative bacilli treated with these 2 therapies also were similar (70% versus 60%, respectively). CONCLUSIONS: In nontertiary care settings, gram-negative bacilli may cause fewer episodes of nosocomial pneumonia (26% in this study) than noted by previously published reports, which indicated that these organisms account for 50% of nosocomial pneumonias. Further, S pneumoniae and H influenzae may account etiologically for many of these nosocomial pneumonias. Monotherapy with an extended-spectrum cephalosporin may be more appropriate than combined treatment with a beta-lactam and an aminoglycoside in a nontertiary care setting, thereby reducing potential toxicity in an older, hospitalized patient population. PMID- 1431000 TI - Outbreak of surgical wound infections associated with total hip arthroplasty. AB - OBJECTIVES: Describe an outbreak of surgical wound infections associated with total hip arthroplasty; identify risk factors for surgical wound infection during the pre-outbreak and outbreak periods. SETTING: A 100-bed hospital. From May 1 to September 30, 1988, 7 of 15 patients who underwent total hip arthroplasty developed surgical wound infections from Staphylococcus aureus (5), Enterobacter cloacae (1), beta-hemolytic streptococci (1), enterococci (1), coagulase-negative staphylococci (1), and Escherichia coli (1) (attack rate = 46.7%). DESIGN: Retrospective cohort studies comparing surgical wound infection rates by patient- and procedure-related risk factors during the pre-outbreak and outbreak periods were conducted. Drop plate quantitative air culturing was conducted in 10 consecutive total hip arthroplasties in the subsequent 6 months. RESULTS: Rates of surgical wound infection were surgically higher for arthroplasties in which no intraoperative prophylactic antimicrobials were given (44% versus 8%, relative risk [RR] = 5.4, p = .01), or in which the posterior approach (20% versus 3%, RR = 6.7, p = .04) or a specific prosthesis (39% versus 5%, RR = 6.3, p = 0.01) was used. The surgical wound infection rate was highest when one circulating nurse, Nurse A, assisted (47% versus 4%, RR = 12.8, p less than .001). Logistic regression analysis identified use of the posterior approach (RR = 1.8, p = .04) and Nurse A's participation (RR = 5.0, p less than .001) as independent risk factors for surgical wound infection. Interviews of the nursing supervisor indicated that Nurse A had recurrent dermatitis on her hands. During 6 months following Nurse A's reassignment, the rate declined significantly (from 7/15 to 0/10, p = .01). Drop plate culturing yielded 2 to 10 colonies per plate of organisms that did not match outbreak organisms. CONCLUSIONS: Outbreaks associated with personnel generally involve only 1 species. In this outbreak, Nurse A (possibly because of her dermatitis), technique, the posterior approach, and/or other undetermined factors were the primary predictors of surgical wound infection. PMID- 1431001 TI - Infections and infection risks in home care settings. AB - OBJECTIVES: To describe the characteristics of home healthcare clients with respect to infection risks and the presence of infections. DESIGN: Descriptive survey of client charts using a point prevalence design. SETTING: A private San Francisco, California, Bay area home care agency. PARTICIPANTS: A random sample of 175 clients (28%) was taken from the active client list for a single day; demographic data and clinical data from the last visit prior to the selection day were collected from each chart. RESULTS: The clients were predominantly elderly (mean = 68.6) with an average of 3.6 co-morbid conditions; 12% had an invasive device. Over 20% had an infection on the day surveyed. Five percent had an infection that occurred during home care delivery. CONCLUSIONS: A substantial proportion of home health clients have infections, and they represent persons with a number of the risks associated with infections. Guidelines for defining and monitoring infections in home care need to be developed. Hospital-based surveillance methods are not altogether appropriate in this setting; redesigning methods such as targeted surveillance, monitoring rehospitalization, or immunization practices are discussed as potential ways to measure quality of care in the home setting. PMID- 1431003 TI - An epidemiologic approach to quality improvement, quality assurance, and clinical research. PMID- 1431002 TI - Needlestick injury in hospital personnel: a multicenter survey from central Italy. The Latium Hepatitis B Prevention Group. AB - OBJECTIVES: To assess the rate of needlestick injury in hospital personnel in an Italian region. To identify risk factors potentially amendable to correction. DESIGN: Hospital workers undergoing hepatitis B prevaccination testing in 1985 through 1986 were interviewed regarding needlestick injury in the previous year, job category, area of work, years of employment, and other pertinent information. SETTING: Of the 98 public hospitals of the Latium region, 68 participated in the survey: 32 of 55 with less than 200 beds, 20 of 25 with 200 to 300 beds, 11 of 13 with 400 to 900 beds, and all of the 5 with more than 1,000 beds. PARTICIPANTS: All healthcare workers providing direct patient care or environmental services as well as student nurses were invited by the hospital directors to undergo hepatitis B prevaccination testing and vaccination, if eligible. RESULTS: Of 30,226 hospital workers of the 68 participating hospitals, 20,055 were interviewed (66.3%): 47.7% of the 7,172 doctors, 71% of the 14,157 nurses, 55.9% of the 2,513 technicians, and 71.9% of the 6,384 ancillary workers. Needlestick injury was recalled by 29.3%; the rates were 54.9%, 35.3%, 33.8%, 26.5%, 18.7%, and 14.7% in surgeons, registered and unskilled nurses, physicians, ancillary workers, and technicians, respectively. The recalled injury rate was 39.7% and 34.0% in surgical and intensive care areas; in infectious diseases, it was 16.7%. Rates were lower in hospitals with 200 to 300 beds (25.6%). The needlestick injury rate declined from 32% in those with less than 5 years of employment to 28% in those with more than 20 years (p less than .01). Prevalence of HBV infection was higher in student nurses and young workers recalling a needlestick exposure (14.3% and 15.8%, respectively), versus 10.1% and 12.8% in those not exposed (p less than .01 and less than .05, respectively). CONCLUSIONS: Parenteral exposure to blood-borne infectious agents is a relevant risk among healthcare workers in our region, particularly in defined job categories and hospital areas (surgeons, nurses, surgical, and intensive care areas). Immunization and educational efforts should be made along with better designs of devices to reduce the risk of infection. PMID- 1431004 TI - The merits of confidence intervals relative to hypothesis testing. PMID- 1431005 TI - Persistent, unusual gram-negative bacteremia associated with arterial pressure monitoring in a pediatric intensive care unit. PMID- 1431006 TI - Introductory comments: a brief history of the development of paroxetine. AB - In the late 1960s research was begun to develop antidepressant agents that would be selective inhibitors of serotonin reuptake. The antidepressants then available, the tricyclic antidepressants, inhibited the reuptake not only of serotonin but also of other monoamines such as noradrenaline--and it is this activity, together with anticholinergic actions, that is responsible for many of the adverse effects such as cardiac toxicity. After much chemical research a family of antidepressants with similar pharmacological activity but disparate chemical structure was developed by several medicinal research laboratories. Because the selective serotonin reuptake inhibitors are chemically different they do not possess the common structural side-effect profile of the tricyclic antidepressants. PMID- 1431007 TI - A double-blind comparison of paroxetine and placebo in the treatment of depressed outpatients. AB - A double-blind, placebo-controlled, randomized trial was carried out to compare the efficacy and tolerability of paroxetine in outpatients with moderate to moderately severe depression without mania. Paroxetine was found to be an effective antidepressant drug when compared to placebo. For most of the measures of efficacy the benefit appeared after two weeks of therapy, but sleep was improved after one week. Patients taking paroxetine complained of more adverse effects than those on placebo; they were mainly gastrointestinal with nausea the most commonly reported. PMID- 1431008 TI - A double-blind comparison of paroxetine, imipramine and placebo in depressed outpatients. AB - Diagnostic criteria, random parallel placebo-controlled study design, and appropriate clinical assessment for both safety and efficacy are all among the essential requirements for the evaluation of a new antidepressant agent. Paroxetine and imipramine were compared for efficacy and safety in a large multicentre, randomized, placebo-controlled, double-blind, parallel design study in the USA. The study involved 717 outpatients with major depressive disorder; after a one-week washout period they were treated for 6 weeks, being assessed at weekly intervals. The results from all six participant centres combined showed that both active drugs were statistically superior to placebo by week 2 and that the antidepressant response was significant for both. Paroxetine was better tolerated than imipramine with fewer dropouts from side effects. This combined study clearly indicated that paroxetine was an effective and well-tolerated antidepressant. PMID- 1431009 TI - A double-blind multicentre study of paroxetine and amitriptyline in depressed outpatients. Italian Paroxetine Study Group. AB - A comparative double-blind study of paroxetine and amitriptyline in the treatment of depressed hospital outpatients was undertaken at 15 centres in Italy. Three hundred and nine patients of either sex were admitted to the study. The starting dose of paroxetine was 20 mg daily and of amitriptyline 75 mg daily in divided doses; at week 3 these doses could be increased at the investigators' discretion. Efficacy was measured on the Hamilton Depression Rating Scale and on Clinical Global Impression. Both treatment groups showed significant improvement at week 6 with no significant between-group differences. Significantly fewer patients receiving paroxetine reported adverse events compared with those on amitriptyline (44% vs 62%; p < 0.01 in favour of paroxetine). PMID- 1431011 TI - Serotonin in affective disorders. AB - Serotonin (5-hydroxytryptamine; 5-HT) is a signalling molecule within the central nervous system. Overall, the impression gained from biochemical, pharmacological, and neuroendocrine studies is that 5-HT synthesis or function is reduced in the brains of depressed patients. There is more direct evidence from animal studies and indirect evidence in man that drugs (and electroconvulsive therapy--ECT) which are efficacious in various facets of affective disorders have clear effects on 5-HT function. 5-HT function is complex. There are at least seven different 5 HT receptor subtypes, several anatomically different 5-HT neuronal tracts emanating from the raphe nuclei in the pons/medulla and projecting widely throughout the brain and downwards into the spinal cord. There are fine mechanisms controlling almost every aspect of function in the 5-HT neurone and the action of 5-HT released from it. There is ample scope for 5-HT to influence many areas of the brain involved in psychological, cognitive, sensory, autonomic, neuroendocrine, and emotional function. Inhibition of reuptake by drugs selective for 5-HT, such as paroxetine, has important acute and chronic effects on 5-HT systems and function, and upon other neurotransmitter systems with which 5-HT interacts. It is of great interest that selective and non-selective monoamine uptake blocking agents, monoamine oxidase inhibitors, lithium and ECT, all affect 5-HT function, albeit slightly differently, and that they should be efficacious in various aspects of affective illness. PMID- 1431010 TI - Paroxetine in the treatment of elderly depressed patients in general practice: a double-blind comparison with amitriptyline. AB - A total of 101 patients entered a double-blind, parallel-group study in general practice, comparing the efficacy and tolerability of paroxetine and amitriptyline in elderly depressed patients. All patients received placebo for 1 week followed by active therapy for a total of 6 weeks. Medication was randomly allocated, two thirds of the patients took paroxetine (20 mg daily) and one-third received amitriptyline (50 mg daily); this dose was increased to 30 mg and 100 mg, respectively, after 1 week. Of the patients who entered the placebo run-in, 90 took active treatment and were evaluable on an intention-to-treat basis (56 paroxetine, 32 amitriptyline). The mean age of the patients was 72 years. Significant reductions in Hamilton Depression Rating Scale (HAMD) from baseline to the end of treatment were seen for both groups (p < 0.01), with no difference between treatments. The HAMD score was reduced by half, or more, for 76% of patients taking paroxetine and 86% taking amitriptyline. Significant improvement was observed in the investigators' Clinical Global Impression (CGI) score for 57% of patients taking paroxetine and 52% on amitriptyline. Improvements after treatment were also observed in the Leeds Sleep Evaluation Questionnaire (LSEQ) scores. Significantly fewer patients taking paroxetine reported adverse events (34% vs 63% taking amitriptyline, p = 0.02). Those taking paroxetine experienced significantly fewer anticholinergic side effects (7% vs 25% taking amitriptyline, p = 0.04). Overall, this study confirmed the effectiveness of paroxetine as an antidepressant drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431012 TI - Sleep and paroxetine: a comparison with mianserin in elderly depressed patients. AB - A total of 60 patients aged 65 years and over who were suffering from unipolar depression were entered into a double-blind 6-week comparative study of paroxetine and mianserin. Assessments of efficacy of treatment included the Hamilton Depression Rating Scale, Clinical Global Impression, and the Leeds Sleep Evaluation Questionnaire. The results showed that the two drugs had equal and acceptable clinical efficacy. There was a similar overall incidence of spontaneously reported adverse events, but with clearly different profiles and a suggestion that mianserin was associated with more anticholinergic effects. In terms of sleep, the study provided evidence of a more beneficial effect from paroxetine. PMID- 1431013 TI - Cardiovascular effects of antidepressants: studies of paroxetine in healthy men and depressed patients. AB - The classical tricyclic antidepressant drugs effectively relieve the symptoms of depression, but they have the potential to be severely toxic to the cardiovascular system--including postural hypotension after therapeutic doses and lethal arrhythmias after overdosage. Paroxetine has been shown to be of similar efficacy to the tricyclic antidepressants but has lower cardiovascular toxicity in animal models and has no effects on heart rate, blood pressure or the electrocardiogram in healthy men receiving single 20-40 mg doses. The results of two contrasting studies in depressive patients and healthy men provide strong evidence that therapeutic doses of paroxetine lack any important haemodynamic or electrophysiological effects. PMID- 1431014 TI - A review of the psychomotor effects of paroxetine. AB - Studies on the behavioural effects of paroxetine on healthy young volunteers, elderly volunteers, and patients suffering from major depressive illness failed to show any evidence of detrimental effects on a battery of objective and subjective measures even when alcohol was taken. In contrast, the chosen verum, amitriptyline or lorazepam, produced significant impairment. The study on depressed patients showed improvement in cognitive functions among the paroxetine group from the start, whereas these functions were, initially, significantly impaired in the dothiepin group. Moreover, the Leeds Sleep Evaluation Questionnaire indicated that dothiepin produced, with respect to paroxetine, a significantly poorer quality of sleep. PMID- 1431015 TI - Paroxetine: an overview of dosage, tolerability, and safety. AB - Paroxetine is a new selective serotonin reuptake inhibitor which has been extensively evaluated as an antidepressant in clinical trials and a large computerized safety database has been accumulated. A comprehensive review of data on dosage supports the recommendation that 20 mg paroxetine daily is the optimal therapeutic dose for most patients. When compared to active controls--mainly tricyclic antidepressants--paroxetine was found to have a different adverse-event profile with fewer anticholinergic, cardiovascular and nervous system events but more gastrointestinal events, particularly nausea. However, these events were not severe and did not usually lead to discontinuation of treatment. The adverse events reported with paroxetine were most likely to occur early in the course of treatment and there was no evidence of any increase in events in the elderly or with longer-term treatment. Paroxetine was not associated with excess of death from any cause, suicides, suicide attempts or serious life-threatening events. No clinically significant drug-related abnormalities were reported in laboratory monitoring, including liver function tests, in short- or long-term use. Finally, and importantly for an antidepressant, paroxetine appears relatively safe in overdose. PMID- 1431016 TI - The anti-anxiety and anti-agitation effects of paroxetine in depressed patients. AB - A worldwide database was employed to assess the effect of paroxetine on symptoms of anxiety and agitation associated with depression. Data derived from the use of paroxetine (n = 2963), placebo (n = 554) and active control (n = 1151) in short term clinical trials were compared. Paroxetine and active control were significantly better than placebo in reducing psychic anxiety. However, paroxetine was superior to active control from week 2 onwards. Both paroxetine and active control had a beneficial effect on somatic anxiety, but this effect was seen earlier with active control. Neither paroxetine nor active control caused emergent (new) anxiety symptoms. Paroxetine had a more robust effect in reducing baseline symptoms of agitation when compared with active control, while both therapies protected from emergent (new) agitation, when compared with placebo. There was no difference between the three groups in the spontaneously reported adverse events indicative of increased arousal. The use of major and minor tranquillizers in the paroxetine and active control groups was similar. PMID- 1431017 TI - The advantages of paroxetine in different subgroups of depression. AB - Paroxetine is a selective serotonin reuptake inhibitor that is now licensed in various countries in Europe. It has comparable efficacy with the reference tricyclic antidepressants and is well tolerated with few adverse effects which are usually mild, transient and do not appear to compromise treatment. Paroxetine has a number of advantages as an antidepressant; of particular interest is its ability to improve sleep early in treatment without daytime sedation or interference with psychomotor function. Paroxetine appears effective compared with placebo in different subgroups of depression: it is effective in both endogenous and reactive depression, as well as being effective in moderate and severe depression. Paroxetine appears particularly effective in treating the anxiety associated with depression and has been shown to have greater efficacy than imipramine. There is some evidence that the onset of antidepressant action occurs slightly earlier with paroxetine than with imipramine. As well as being effective in the acute episode, placebo-controlled, long-term data are available indicating paroxetine to be of value in the prevention of depressive relapse. PMID- 1431018 TI - Clinical pharmacokinetics of citalopram and other selective serotonergic reuptake inhibitors (SSRI). AB - The pharmacokinetics and clinical properties of clomipramine, the classic 5-HT uptake inhibiting antidepressant is well known. Within the last years, several new and more selective serotonin uptake inhibitors have been introduced in clinical practice, including trazodone, citalopram, paroxetine, femoxetine, fluvoxamine and fluoxetine. They differ by their chemical structure, and therefore, important differences can be expected with respect to their metabolism and kinetics in man. In this presentation, the following points will be addressed: Present knowledge about their metabolism and their kinetics, taking into account that most of them are racemates, whose clinical role is only partially understood, including that of the metabolites. It will further be examined whether they are candidates for a genetic polymorphism of metabolism of the debrisoquine-spartein-dextromethorphan type. This may e.g. be suspected for fluoxetine which interferes strongly with the metabolism of tricyclic antidepressants. Finally, data of the literature will be analysed about a possible relationship between the clinical efficacy of these drugs and their plasma levels, including those of their active metabolites. PMID- 1431019 TI - Serotonin, panic disorder and agoraphobia: short-term and long-term efficacy of citalopram in panic disorders. AB - A serotonin-anxiety connection has been widely recognized. In panic disorder (PD), however, most researchers have emphasized noradrenergic mechanisms. Serotonin related findings in PD, e.g. the documented antipanic potential of selective serotonin reuptake inhibitors (SSRIs), are reviewed, lending support for a serotonergic deficit contributing to the pathophysiology of PD. Since citalopram is the most selective SSRI described, it was chosen as a tool for testing whether the serotonin reuptake inhibition per se is responsible for this antipanic effect. Twenty patients with PD with or without agoraphobia (DSM-III-R criteria) were treated openly with citalopram and assessed with CAS, MADRS, SCL 90 the Agoraphobia Scale, other self-ratings, and a panic diary. Thirteen of the 17 patients completing 8 weeks of treatment were judged as responders. The response seemed similar to or better than that seen with other antidepressants. The response covered broad aspects of morbidity, e.g. anticipatory anxiety, agoraphobia and somatization. In the first week, a transient increase of panic related symptoms was observed. Sixteen of the patients were enrolled in a 15 months' study of long-term maintenance treatment; 11 patients completed this phase. The gains were maintained during this follow-up, and further improvement was observed. Side-effects were similar to those of other SSRIs and mostly mild. For instance, weight-gain was not associated with citalopram treatment. The results support the hypothesis that serotonin reuptake inhibition is essential for the antipanic effect of antidepressants as well as for the initial paradoxical increase of anxiety often seen with these drugs. Thus, an initial deterioration, possibly due to transient decrease of serotonin transmission, turns to improvement when serotonergic potentiation has occurred. PMID- 1431020 TI - New aspects in the treatment of depression. AB - Because of the limitations in efficacy and safety of the older tricyclic antidepressants (TCA) and monoamine oxidase inhibitors (MAOI) a number of new approaches have been made in recent years to the treatment of depression to obtain more effective, more rapidly acting, better tolerated and safer drugs. One tactic has been to develop compounds with greater neuropharmacological selectivity in inhibiting the neuronal reuptake of 5-HT. Most of these are as effective as TCA but with fewer side-effects and greater safety. Another development has been 'reversible' MAOI which reduce the risk of interaction with tyramine-containing foods. For resistant depression the addition of lithium (and/or tryptophan) may be effective, possibly through promoting 5-HT neurotransmission. Continuous treatment with a selective 5-HT reuptake inhibitor can reduce the relapse rate in patients with recurrent depression. Unfortunately, these new approaches, despite their advantages in terms of side-effects and safety, have thus far not proved to be more effective or faster acting than the standard TCA. That remains a challenge for the future. PMID- 1431021 TI - Citalopram in depression--meta-analysis of intended and unintended effects. AB - An updated qualitative meta-analysis of controlled clinical trials is presented. When compared to reference drugs, especially tricyclics, citalopram after 6 weeks of treatment showed a similar intended effect on the depression index of the Hamilton scale. However, on the sleep index of the scale citalopram was weaker than tricyclics. When compared to placebo, citalopram after 6 weeks of treatment showed to be significantly superior on the Hamilton scale and on the global assessment scales. Analysis of unintended effects showed that citalopram had fewer side-effects than tricyclics, especially of anticholinergic types. In conclusion, citalopram has been found to be a non-sedating antidepressant which is well accepted by the patients due to its lack of unintended effects. PMID- 1431022 TI - Potential indications for the selective serotonin reuptake inhibitors. AB - The selective serotonin reuptake inhibitors (SSRIs) include fluoxetine, fluvoxamine, citalopram, paroxetine and sertraline. These medications may be effective for a variety of indications. The literature clearly supports their efficacy in some of these conditions in major depression. Data concerning their use in other areas is clearly preliminary but promising. These include reports of treatment of obsessive-compulsive disorder, atypical depression, panic disorder, premenstrual tension, eating disorders, substance use disorders, chronic pain, dementia, and personality disorders with aggressive or impulsive features. The variety of clinical uses for the SSRIs may compel re-examination of traditional diagnostic categories and theories of how antidepressants work. PMID- 1431023 TI - Treatment of depression in elderly patients with and without dementia disorders. AB - In two inter-Nordic multicenter controlled studies the effect of Citalopram on elderly patients with depression and emotional disturbances has been studied. One investigation included 98 patients in whom Alzheimer type dementia (AD/SDAT) and vascular dementia (VD) had been diagnosed, many of whom also had emotional disturbances. After four weeks treatment with Citalopram (10-30 mg/daily) there was significant improvement in confusion, irritability, anxiety, depressed mood and restlessness. No effect was seen on the intellectual capacity or motor performance measured. In the other study, which was a six weeks trial comparing Citalopram and placebo, elderly patients with a treatment-requiring depression were treated. Demented as well as non-demented patients were included. The Hamilton Depression Scale, the Montgomery-Asberg Depression Rating Scale and The Clinical Global Impressions all recorded an effect of Citalopram superior to that of placebo. In both studies depressive symptoms as well as symptoms of agitation, anxiety, restlessness and irritability improved. Citalopram is therefore considered not only an antidepressive drug but also an emotional stabilizer. The drug was well tolerated by elderly often somatically ill patients. Side effects were few. PMID- 1431024 TI - Dose response relationship of citalopram 20 mg, citalopram 40 mg and placebo in the treatment of moderate and severe depression. PMID- 1431026 TI - Epidemiology of suicide. PMID- 1431025 TI - Citalopram 20 mg, citalopram 40 mg and placebo in the prevention of relapse of major depression. PMID- 1431027 TI - Toxicity of antidepressants: comparisons with fluoxetine. AB - Antidepressant drugs have been available for 30 years. Although effective and useful in restoring quality of life, the older drugs in particular have many unwanted properties. The anticholinergic effects of the tricyclic drugs are a major drawback, and the risk of interactions limits the usefulness of the monoamine oxidase inhibitors (MAOIs). Generally, newer drugs including fluoxetine have a more favourable adverse effect profile. Although a number of drugs produce rare but serious adverse effects, overdose toxicity is a matter of greater importance, especially in patients who are at risk of suicide. Toxicity indices, calculated from the number of deaths per million prescriptions for each drug, enable comparisons between drugs to be made. These show that several of the older tricyclic drugs have relatively high mortality in overdose. Many of the newer drugs including fluoxetine have a good record of safety in overdose, and this forms an important part of their risk-benefit profile. PMID- 1431028 TI - The provocation and prevention of suicide attempts. PMID- 1431029 TI - On bloodborne pathogens. PMID- 1431030 TI - National health care: Panacea or Pandora's box? PMID- 1431031 TI - IAFP leader dispels myths of family medicine. Interview by Bob Carlson. PMID- 1431033 TI - HIV/AIDS surveillance in Indiana. PMID- 1431032 TI - Vagueness of OSHA rules concerns physicians. PMID- 1431034 TI - Helping patients receive Social Security benefits. PMID- 1431035 TI - The Bethesda System and patient management strategies. PMID- 1431036 TI - Operative management of intra-abdominal infections. AB - Operation for intra-abdominal infection aims to prevent further contamination of the abdominal cavity, treat the underlying source of infection, and prevent residual or recurrent sepsis by cleaning the peritoneal cavity. Aggressive attempts at early diagnosis are warranted, even if laparotomy is occasionally required for diagnostic as well as therapeutic purposes. Conversely, the degree to which more aggressive methods of peritoneal debridement are helpful is the subject of great controversy that can be resolved only by prospective, randomized multicenter trials. Current standard treatment consists of closure, drainage, or excision of the source of contamination; intra-operative saline or antibiotic lavage of the peritoneal cavity; fascial closure; and secondary or delayed primary closure of the wound. PMID- 1431037 TI - Percutaneous versus open operative drainage of intra-abdominal abscesses. AB - This article has tried to provide some perspective on the results of surgical and percutaneous drainage of intra-abdominal abscesses and the impact of CT localization on the successful management of this problem. It is most likely that the recent decrease in mortality for intra-abdominal abscesses over the past decade is due to a variety of factors, including better antibiotics, more aggressive critical care, and earlier diagnosis and treatment of the intraabdominal problem. These factors combined to reduce the incidence of pre drainage organ failure and the degree of physiologic derangement of these patients at the time of their abscess drainage. Percutaneous drainage and surgical drainage techniques should not be considered competitive but rather complementary. If an abscess is accessible by percutaneous techniques, it is reasonable to consider a nonoperative approach to the problem. It is also clear that patients should respond promptly to whatever technique is employed to drain their intra-abdominal abscess. An improvement should be seen clinically within 24 to 48 hours following drainage. Should improvement not be forthcoming, the patient must be aggressively re-evaluated with repeat CT and decisions made by the responsible surgeon in consultation with the radiologist as to the next appropriate course of action. As our review of the Wayne State University experience suggested, patients are never too sick for an appropriate operation. Although it appears that most abscesses can be successfully treated by percutaneous drainage, pancreatic abscesses with pancreatic necrosis should generally be treated by surgical debridement, usually accompanied by repeated explorations. In addition, splenectomy has not yet been replaced by percutaneous drainage of splenic abscesses. PMID- 1431038 TI - Antimicrobial therapy of intra-abdominal sepsis. AB - Intra-abdominal sepsis remains a highly morbid and lethal event despite the availability of potent antimicrobial agents and improvements in surgical management and intensive care. Appropriate management consists of source control, antimicrobial agents directed against both facultative gram-negative and anaerobic organisms, and physiologic and metabolic support. A variety of single and dual agent regimens are appropriate for initial therapy, as long as both aerobes and anaerobes are effectively targeted. Culture, Gram stain, and sensitivity testing may provide valuable information, especially when resistant organisms are encountered. Further studies to determine the relative efficacy of various agents need to be carefully designed both to avoid the pitfalls of previous studies and to provide useful and comparable data. PMID- 1431039 TI - Acute cholangitis. AB - Acute cholangitis is a clinical syndrome marked by fever, jaundice, and abdominal pain that develops because of stasis and infection in the biliary tract. Patients with cholangitis may present with symptoms ranging from a mild, recurrent illness to overwhelming sepsis. Increased age, malignant obstruction, and a rapidly progressive, systemic illness define a group of patients at increased risk. Patients who are delayed in diagnosis, present with septicemia, or fail to respond to conservative treatment still have substantial morbidity and death from cholangitis. Antibiotic therapy that includes coverage for anaerobes and gram negative, enteric organisms together with other supportive measures often resolves the acute episode, permitting elective diagnostic procedures prior to definitive treatment of biliary tract obstruction. Advances in endoscopic and transhepatic procedures have reduced the necessity for and risks associated with emergent operative biliary drainage. PMID- 1431040 TI - Infections complicating severe pancreatitis. AB - Infections accompanying severe pancreatitis are secondary and of three types: infected pancreatic necrosis, infected pseudocyst (including peripancreatic fluid collection), and pancreatic abscess. The first is an earlier, more morbid process, with antibiotics supportive and surgical debridement necessary. The latter two processes occur later in the course of pancreatitis and are less morbid. Antibiotics are supportive and invasive-nonsurgical drainage methods are possible. The decision for intervention is based first on clinical toxicity as determined by an overall assessment by the clinician. The presence of parenchymal necrosis is best determined by the dynamic bolus CT scan. The presence of infection is best determined by percutaneous CT-guided aspiration. Infected necrosis is fatal unless treated with operative intervention. A peripancreatic fluid collection, pseudocyst, or pancreatic abscess needs to be treated if symptomatic. If infected, as determined by CT-guided needle aspiration, then they should be drained. Radiologic or endoscopic invasive-nonsurgical methods are tried initially and then surgery is attempted if they fail. The nonsurgical methods are most successful with pancreatitis of a nonbiliary or a nonalcohol etiology. PMID- 1431041 TI - Antibiotic prophylaxis for scheduled operative procedures. AB - As a result of numerous trials during the past two decades addressing antibiotic prophylaxis for surgical procedures, it has been established that appropriately administered antibiotic prophylaxis reduces the risk of postoperative infection by about 50% when compared with comparable untreated patients. Antibiotics cannot completely eliminate all risk of infection, however, and will never be a substitute for good surgical practices. PMID- 1431043 TI - Wound infection surveillance. AB - Wound infection surveillance is the information-gathering arm of a wound infection control program. Wound infection control concerns prevention--not therapy--of an infrequent but expensive kind of surgical morbidity. Topics discussed in this article include the effectiveness of wound infection surveillance; turf issues; phenomenology; and the gathering, reporting, manipulating, and use of wound infection data. PMID- 1431042 TI - Antibiotic prophylaxis for injured patients. AB - Infection is the major cause of serious complication in injured patients. This article addresses antibiotic use in the injured patient and clarifies the limitations of antimicrobials in the prevention of infection. PMID- 1431044 TI - Nosocomial infection in the surgical intensive care unit. AB - The critically ill surgical patient is at high risk for the development of ICU acquired infection. Normal mucosal defenses are breached by surgical incisions or by intravascular devices, urinary catheters, and endotracheal tubes. The integrity of the gastrointestinal epithelium is compromised by the lack of enteral nutrition and episodes of hypoperfusion, resulting in translocation of normal or disturbed enteric flora. The indigenous microbial flora, an important component of normal host defenses against invasive infection, is disrupted through the use of broad-spectrum antibiotics or by poorly understood influences associated with critical illness. Systemic immunity is altered, and multiple abnormalities of specific and nonspecific immune function can be documented. Infections acquired within the ICU are commonly caused by endogenous organisms of low intrinsic pathogenicity, and the contribution of these infections to ICU outcome is controversial. Diagnosis is established by directed investigations, focusing on surgical sites and invasive devices. Therapy is primarily physical (drainage of infected collections or removal of contaminated devices), and antimicrobial therapy should employ narrow-spectrum agents guided by the results of Gram stain and culture. The prevention of ICU-acquired infection is based on timely and definitive surgical therapy, judicious use of invasive devices and antibiotics, and early enteral feeding. Infection-control measures aimed at endogenous reservoirs show some preliminary promise for certain subsets of patients, but remain, at present, experimental. PMID- 1431045 TI - Fungal sepsis. AB - Immunocompromise can result from trauma, burns, cancer, cancer chemotherapy, and immunosuppressive therapy. Immunocompromise increases the risk of invasive infection from opportunistic fungi. The key to successful management of these infections is early recognition, aggressive therapy, and when indicated, surgical therapy. This article describes the common opportunistic fungal infections aspergillosis, zygomycosis, and candidiasis, which may arise in surgical patients or which may require surgical intervention for diagnosis or therapy. PMID- 1431046 TI - Necrotizing soft-tissue infections. AB - Necrotizing soft-tissue infections have been widely recognized for over a century, but they remain a challenging problem in clinical infectious disease. Patterns of disease are clearly apparent, but most are polymicrobial and derive increased virulence from synergy between bacteria. Early recognition and prompt surgical drainage are the keys to successful treatment. Edema extending beyond the area of erythema, skin vesicles, crepitus or air in the subcutaneous tissues, and absence of lymphangitis and lymphadenitis are markers of necrotizing infections, particularly when they occur in patients with serious underlying disease. Empiric broad-spectrum antibiotics, prophylactic heparin, and nutritional therapy are important adjuncts to aggressive "stepwise" surgical debridement. A knowledge of patterns of disease can aid in fine-tuning treatment to decrease morbidity. PMID- 1431047 TI - Abscesses and deep space infections of the head and neck. AB - Abscesses and deep space infections of the head and neck continue to be encountered in clinical practice. Recognition of these processes requires careful physical examination, an adequate index of suspicion, and appropriate application of modern imaging techniques. The principles of management of abscesses are largely unchanged. Space infections must be drained. A specimen should always be submitted for bacteriologic evaluation to allow change in antimicrobial administration when patterns of resistance are identified. Fungal infection should be considered when rhinosinusitis develops in the hospitalized immunocompromised patient. Biopsy of abnormal tissue is the mainstay of diagnosis under these circumstances. Therapy frequently requires surgical debridement in addition to administration of antifungal chemotherapy. PMID- 1431048 TI - Diagnosis and treatment of biomaterial-associated vascular infections. AB - Management of biomaterial-associated vascular infections requires an understanding of pathogenetic mechanisms, risk factors, and microbiologic characteristics. Staphylococci sp., especially slime-producing strains of S. epidermidis are the prevalent pathogens. Experimental and clinical studies have indicated in situ replacement, particularly with an antibiotic-bonded prosthesis, as effective treatment for infections caused by coagulase-negative staphylococci. When sepsis is a presenting sign, prompt intervention, total excision of the prosthesis, and antibiotic administration are required. PMID- 1431049 TI - Infectious complications of blood transfusions. AB - The use of blood and blood products has revolutionized medical care over the last century. Without this capacity, many medical and surgical procedures would not be possible. The safety of these procedures is predicated, in part, on an appreciation of the complications of transfusions, including transmission of infectious disease. Assuring that patients are adequately protected from these hazards while providing the products that they need is the responsibility of both blood banks and practitioners. PMID- 1431050 TI - Surgical care of HIV-infected patients. AB - An increasing number of HIV-infected patients will require surgical therapy. The methods of diagnosis and therapeutic planning for HIV-infected patients are the same as for all other patients. Surgery should be advised if an operation is likely to have a positive effect on the patient's life. Most patients with AIDS with diseases for which surgical therapy is advantageous benefit from carefully chosen operations designed to solve specific problems. PMID- 1431051 TI - Immunohistochemical and immunoelectron microscopic analyses of alpha-amylase isozymes in human intrahepatic biliary epithelium and hepatocytes. AB - The expression and localization of the pancreatic and salivary isozymes of alpha amylase in the intrahepatic biliary epithelium and hepatocytes were examined by the immunohistochemical method with polyclonal and monoclonal antibodies in 45 normal autopsied human livers. Immunoelectron microscopic studies with the protein A-gold method were performed with the monoclonal antibodies (MAb) on seven of the livers. The intrahepatic biliary system was divided into large ducts, septal ducts, interlobular ducts, bile ductules, and peribiliary glands. Immunohistochemically, pancreatic isozyme was observed in the supranuclear cytoplasm of the epithelium of large ducts, septal ducts, and peribiliary glands in almost all livers. Interlobular ducts expressed pancreatic isozyme in only four (9%) livers. Bile ductules and hepatocytes were negative for pancreatic isozyme in all cases. Expression of salivary isozyme was observed in the supranuclear cytoplasm of the epithelium of large ducts, septal ducts, interlobular ducts, bile ductules, and peribiliary glands in almost all livers, although the expression in interlobular ducts and bile ductules was weak. Hepatocytes were weakly positive for salivary isozyme. Immunoelectron microscopy revealed that both pancreatic and salivary isozymes were located in the supranuclear cytoplasm of the epithelium of large ducts, septal ducts, and peribiliary glands, and that hepatocytes had no pancreatic isozyme but contained salivary isozyme. These data suggest that pancreatic and salivary isozymes of alpha-amylase are produced by the intrahepatic biliary epithelium and secreted into intrahepatic biliary lumens, and that they may play an important role in the physiology of the intrahepatic biliary tree and hepatic bile. It is also suggested that hepatocytes produce a small amount of salivary alpha-amylase that may be secreted into the biliary tree. PMID- 1431052 TI - Uptake of maternal immunoglobulins in the enterocytes of suckling piglets: improved detection with a streptavidin-biotin bridge gold technique. AB - In ungulates, intestinal absorption of maternal immunoglobulins from colostrum plays a vital role in the acquisition of passive immunity during early neonatal life. In the present study we used post-embedding colloidal gold labeling to examine the intracellular localization of IgG in the jejunal enterocytes of miniature piglets suckled for 2 hr. Quantitation of the immunolabeling revealed that the most sensitive technique for IgG detection was the streptavidin bridge gold technique. In this method, the LR White-embedded sections were labeled sequentially with biotinylated anti-porcine IgG, streptavidin, and biotinylated BSA conjugated to 10-nm colloidal gold. With this approach, we found the following sequence of maternal IgG accumulation: passage of IgG from colostrum through the brush border; binding to the apical plasma membrane; uptake in noncoated pits and invaginations; transport in endocytotic vesicles; and accumulation in granules in the apical cytoplasm. PMID- 1431053 TI - Electron microscopic detection of RNA sequences by non-radioactive in situ hybridization in the mollusk Lymnaea stagnalis. AB - The subcellular localization of mRNA sequences encoding neuropeptides in neuropeptidergic cells of the pond snail Lymnaea stagnalis was investigated at the electron microscopic (EM) level by non-radioactive in situ hybridization. Various classes of probes specific for 28S rRNA and for the ovulation hormone (caudodorsal cell hormone; CDCH) mRNA were labeled with biotin or digoxigenin and were detected after hybridization with gold-labeled antibodies. Hybridizations were performed on ultra-thin sections of both Lowicryl-embedded and frozen cerebral ganglia, and a comparison demonstrated that most intense hybridization signals with an acceptable preservation of morphology were obtained with ultra thin cryosections. Addition of 0.1% glutaraldehyde to the formaldehyde fixative improved the morphology, but on Lowicryl sections this added fixative resulted in a decrease of label intensity. A variety of probes, including plasmids, PCR products, and oligonucleotides, were used and all provided good results, although the use of oligonucleotides on Lowicryl sections resulted in decreased gold labeling. The gold particles were found mainly associated with rough endoplasmic reticulum (RER) but were also observed in lysosomal structures. Finally, the in situ hybridization method presented in this study proved to be compatible with the immunocytochemical detection of the caudodorsal cell hormone, as demonstrated by double labeling experiments. PMID- 1431054 TI - Light microscopic immunohistochemical analysis of the distribution of group II phospholipase A2 in human digestive organs. AB - The light microscopic and immunohistochemical distribution of human Group II phospholipase A2 (M-PLA2) in digestive organs of both human fetus and adult, with a new monoclonal antibody (MAb) against M-PLA2, was investigated semiquantitatively. The immunoreactivity was distributed similarly in the adult and fetal epithelium of the esophagus, duodenum, and small intestine, and in the acinar, islet, and duct cells of the pancreas. The epithelium of adult gallbladder was immunoreactive. Paneth cells, especially the secretory apparatus, were strongly immunoreactive. Hepatic Kupffer cells and macrophages of the adult spleen were also immunoreactive. These results suggest that these cells contain secretory-type Group II PLA2, which may be involved in host defensive mechanisms, such as phagocytosis in human digestive organs. In the adult colon, the immunoreactivity was observed only in the ascending colon and was not found in the transverse, descending, sigmoid, or rectal colon. The immunoreactivity was not found in fetal colon. Similarly, immunoreactivity was found in hepatocytes and Kupffer cells of adult liver but not in fetal liver. By contrast, strong immunoreactivity was observed in the epithelium of the fetal stomach but not in adult stomach except in gastric neck cells. This suggests that the expression of M-PLA2 may be related to cell differentiation in particular organs. PMID- 1431055 TI - Membrane-associated carbonic anhydrase activity in the kidney of CA II-deficient mice. AB - Carbonic anhydrase II-deficient mice offer a possibility to study the localization along the nephron of membrane-associated carbonic anhydrase (CA) activity without interference from the cytoplasmic enzyme. We studied the localization of CA in kidneys from CA II-deficient and control mice by immunocytochemistry (CA II) and histochemistry. Cytoplasmic staining was found in convoluted proximal tubule, thick limb of Henle, and principal and intercalated cells of collecting duct in the control animals but was absent in the CA II deficient mice. In cells with cytoplasmic staining the cell nuclei were stained. Intense histochemical activity was associated with apical and basolateral membranes of convoluted proximal tubule, first part of thin limb, thick limb, and basolateral membranes of late distal tubule. In collecting ducts of control animals, the basolateral cell membranes of intercalated cells were the only clearly stained membranes. In CA II-deficient animals one type of intercalated cell was stained most intensely at the apical membranes and another only at the basolateral. We suggest that the former corresponds to Type A intercalated cells secreting H+ ions to the luminal side and the latter to Type B cells secreting H+ ions to the basolateral side. PMID- 1431056 TI - Application of two-color immunofluorescence staining to demonstration of T-cells and HLA-DR-bearing cells in rheumatoid synovitis. AB - We studied the localization of T-cells and HLA-DR antigen-bearing (DR+) cells in rheumatoid synovitis by employing an improved two-color immunofluorescent staining (TCIF) technique. With this technique we have successfully identified DR+ activated T-cells in the inflammatory synovium. T-cells expressed HLA-DR antigen when they were in contact with DR+ antigen-presenting cells (APC). In addition, activated T-cells showed characteristic distribution within the synovium: they were found around high endothelial venules, within lymphoid follicles, and in hyperplastic synovial lining, suggesting their involvement in the development of rheumatoid synovial lesions via interaction with synovial DR+ APC lineage cells. These findings may contribute to better understanding of the role of activated T-cells in the histogenesis of rheumatoid synovitis, a typical chronic inflammatory lesion. PMID- 1431057 TI - Demonstration of dopamine-immunoreactive cells in the proximal convoluted tubule of gerbil (Meriones unguiculatus) kidney. AB - We investigated dopamine immunoreactivity in the kidney of gerbils (Meriones unguiculatus). For that purpose a sensitive and selective antibody against glutaraldehyde-conjugated dopamine was applied. Dopamine-immunoreactive cells were found in the epithelium of the proximal convoluted tubule, where these cells revealed a typical segment-like distribution pattern. Dopamine-immunoreactive precipitates were small and concentrated at the apical pole of the labeled cells. This study has directly identified dopamine as a constituent of certain cells of the proximal convoluted tubule in gerbils. The functional significance of dopamine in these cells is discussed in relation to the present view of renal dopaminergic actions. PMID- 1431058 TI - Intra- and extracellular localization of hyaluronic acid and proteoglycan constituents (chondroitin sulfate, keratan sulfate, and protein core) in articular cartilage of rabbit tibia. AB - To demonstrate the intra- and extracellular localization of hyaluronic acid (HA) in articular cartilage of the rabbit tibia, biotinylated HA binding region, which specifically binds to the HA molecule, was applied to the tissue. In comparison with the localization of HA, that of chondroitin sulfate (CS), keratan sulfate (KS), and the protein core (PC) of the proteoglycan was examined by immunohistochemistry. Strong positive staining for HA was detected in chondrocytes located in the transition between the superficial and middle zones of the tissue. Pre-treatment with chondroitinase ABC, keratanase II, or trypsin enhanced the stainability for HA in peri- and intercellular matrices. Immunohistochemistry with or without enzymatic pre-treatment demonstrated that immunoreactivity for CS, KS, and PC was distinctly discerned in chondrocytes and in the extracellular matrix located in the middle and deep zones. In particular, the immunoreactivity for KS and PC was augmented by pre-treatment with chondroitinase ABC not only in chondrocytes but in the extracellular matrix located in the middle and deep zones. Microbiochemical analysis corresponded well with histochemical and immunohistochemical results. These results suggest that HA is abundantly synthesized and secreted in chondrocytes located in the transition between the superficial and middle zones. PMID- 1431059 TI - Immunohistochemical localization of superoxide dismutases in fetal and neonatal rat tissues. AB - We investigated the developmental profile of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in tissue sections obtained from fetal (Day 12 to 21 of gestation) and neonatal (Day 0 and 6) rats. Tissues were stained immunohistochemically with specific antisera against the respective rat SODs. There was a general trend towards richness of SODs in the epithelial linings and metabolically active sites, although differential distribution between the two SODs also existed. At Day 12 of gestation, immunoreactivity for both SODs was detected in the cardiomyocytes but not in other tissues. Hepatocytes expressed CuZnSOD at Day 14 and MnSOD at Day 17. By Day 18 CuZnSOD was detected in the epithelial cells of the gastrointestinal tract, respiratory tract, pancreatic islets, kidneys, and adrenals. These tissues exhibited MnSOD staining at Day 19. CuZnSOD occurred in the epithelia of the thyroid, thymus, and salivary glands at Day 19, while MnSOD was seen at Day 21. The increase in intensity of the staining for SODs occurred no later than postnatal Day 0, indicating that most tissues accumulated SODs during late gestation. Breathing atmospheric oxygen during early extrauterine life did not appreciably intensify the SOD staining. These results suggest that perinatal increase in SODs occurs as a general mechanism of preparation for birth. PMID- 1431060 TI - Complete penetration of antibodies into vibratome sections after glutaraldehyde fixation and ethanol treatment: light and electron microscopy for neuropeptides. AB - To develop a method for quantitative electron microscopic immunocytochemistry on neural tissue of CNS, we tested the extent to which ethanol treatment would improve the penetration of immunoreagents through vibratome sections fixed in high concentrations of glutaraldehyde without compromising ultrastructure. Transverse or sagittal vibratome sections (60-80 microns) of spinal cord perfused with 1% formaldehyde plus 1% or 2.5% glutaraldehyde were washed in 50% ethanol for 0-70 min and stained to reveal immunoreactivity for neuropeptide Y (NPY). Semi-thin (1 micron) or ultra-thin sections were used to assess the depth to which NPY nerve fibers in the dorsal horn were stained. Without ethanol washing, immunoreactive nerve fibers were visualized only in the surface 5-10 microns of transverse or sagittal vibratome sections. In transverse vibratome sections, NPY nerve fibers, which ran perpendicular to the cut surfaces of the sections, were entirely stained after a 30-min wash in 50% ethanol. The numbers of NPY immunoreactive varicosities and synapses were comparable at the surfaces and in the centers of the vibratome sections. In sagittal sections, where NPY nerve fibers ran parallel to the cut surfaces, fibers in the centers of vibratome sections could not be labeled even after 70 min in 50% ethanol. Substance P- and enkephalin (Enk)-immunoreactive nerve fibers could also be completely stained in transverse sections of spinal cord or medulla oblongata after 30-min exposure to ethanol. Ethanol washing had no significant deleterious effects on ultrastructure, although the amount of cytoplasmic matrix in neurons decreased with increasing exposure. These results indicate that washing with 50% ethanol for at least 30 min allows immunoreagents to penetrate completely through nerve fibers fixed with high concentrations of glutaraldehyde, as long as the fibers have cut ends at both surfaces of a vibratome section. This technique makes possible quantitative electron microscopic immunocytochemical studies and is proving a useful tool for defining synaptic connections in the CNS. PMID- 1431061 TI - Nerve-induced secretion of glycoconjugates from cat submandibular glands: a correlative study with lectin probes on tissues and saliva. AB - Horseradish peroxidase-conjugated lectins were used on tissue sections to localize the main secretory glycoproteins in cat submandibular glands and on Western blots to evaluate their movement into saliva with selective nerve stimulation. Central acinar cells bound lectins from Arachis hypogaea (PNA) specific for the terminal disaccharide Gal beta 1, 3GalNac, Griffonia simplifolia (GSA I-B4) specific for terminal alpha Gal, and Lotus tetragonolobus (LTA) specific for fucose. Lectins from Limax flavus (LFA) specific for sialic acid and Dolichos biflorus (DBA) specific for terminal alpha GalNac reacted preferentially with demilunar cells, whereas apical granules in striated ducts were recognized principally by LTA. Parasympathetic stimulation promoted the release of lectin reactive glycoconjugates from both central and demilunar cells. In contrast, sympathetic stimulation caused almost complete release of LTA-reactive granules in striated ducts and only moderate secretion from demilunar cells. Lectin blots of stimulated saliva discriminated many of the constituent bands, providing information about their glycosylation. Several bands were common to both parasympathetic and sympathetic saliva, and many bands gave wider ranges of lectin binding than anticipated from the histochemistry. The major component in parasympathetic saliva was a glycoconjugate of less than 12 KD which reacted with every lectin tested. Lectin blots of sympathetic saliva showed a prominent diffuse LTA-reactive band around 33 KD, which was attributed to tissue kallikrein. The identity and cellular origin of most bands in stimulated submandibular saliva are still unclear but the technique shows considerable promise for improving the recognition and characterization of individual glycoconjugates. PMID- 1431062 TI - Expression of the first calcitonin/CGRP gene in spontaneous and transplanted rat medullary thyroid carcinoma: a comparison of dot-blot analysis, in situ hybridization, and immunohistochemistry. AB - Calcitonin (CT) and calcitonin gene-related peptide (CGRP) are encoded by a single gene, the CALC-I gene. They are expressed in the thyroid and in the nervous system by alternative splicing of the pre-messenger RNA derived from the CALC-I gene. In medullary thyroid carcinoma (MTC), a malignancy derived from the calcitonin-producing C-cells in the thyroid, production of calcitonin and CGRP is a common feature. We investigated the CT and CGRP production of four spontaneous MTCs transplanted three to four times and 14 MTC lines transplanted for several years in WAG/Rij rats, a strain with hereditary MTC. The expression of CT and CGRP in the spontaneous and in the transplanted tumors was studied by means of RNA in situ hybridization (RISH), dot-blot analysis, and immunohistochemistry. A down-regulation of CT production in transplanted compared with spontaneous tumors was observed, but an inverse relation between CT and CGRP mRNA content in both spontaneous and transplanted tumors was not observed. In this study, RISH proved to be as sensitive as dot-blot analysis to detect gene expression in tissue samples. The different approaches of analyzing the gene expression in tissue samples (the cellular localization of gene expression by ISH vs the analysis of an extract of a total tissue sample with dot-blot analysis) showed that each technique is equal in value and that they are complementary to each other. PMID- 1431063 TI - Nature and distribution of mineral-binding, keratan sulfate-containing glycoconjugates in rat and rabbit bone. AB - The presence of keratan sulfate (KS) and KS proteoglycans in bone has been demonstrated in birds and rabbits but comparison with other animal species has not been investigated. The nature and distribution of mineral-binding, KS containing glycoconjugates in rat and rabbit bone were investigated with a monoclonal antibody (MAb 5D4) specific for KS. Mineral-binding proteins were extracted from the mineralized bone with 0.4 M EDTA without guanidine-HCl (E extract). On Western blot analysis of SDS-polyacrylamide gel electrophoresis, rat E-extract gave a weak 5D4-reactive band, M(r) 66,000-68,000, whereas rabbit E extract produced two major reactive populations of small and large molecular size; one population consisted of two closely spaced bands at M(r) 61,000-63,000 and 66,000-68,000, and the other population consisted of one band at approximately M(r) 200,000. The identity of KS chains was further established by the sensitivity of these bands to keratanase II (Bacillus sp. Ks 36) and endo beta-galactosidase. Immunocytochemistry with MAb 5D4 showed that, in rat bone, staining associated with the mineral phase was limited to the walls of osteocytic lacunae and bone canaliculi, whereas the remainder of the mineralized matrix lacked staining. In contrast, in rabbit bone the staining was distributed over the entire portion of the mineralized matrix with focal accumulation of staining in the wall of the lacunocanalicular system. These results indicate that rat bone contains a mineral-binding, KS-containing glycoconjugate with preferential localization in the wall of the lacunocanalicular system, whereas rabbit bone contains at least two or possibly three types of KS-containing glycoconjugates distributed over the entire portion of the mineralized matrix. PMID- 1431064 TI - Fluorescence image cytometry of nuclear DNA content versus chromatin pattern: a comparative study of ten fluorochromes. AB - This study is intended to be the first step of an in situ exploration of the intranuclear DNA distribution by image cytometry (SAMBA) with several fluorochromes. The nuclear DNA content and the chromatin pattern, revealed by ten fluorochromes (HO, DAPI, MA, CMA3, OM, QM, AO, EB, PI, and 7-AMD), were analyzed on mouse hepatocytes fixed by the Boehm-Sprenger procedure optimal for preserving the chromatin pattern. The question was whether fluorochromes specific to DNA make it possible to accurately quantitate the total nuclear DNA content when the chromatin pattern is preserved. Only HO and MA were found to provide satisfactory quantitation of nuclear DNA content, as assumed by both a small CV and a 4c to 2c ratio equal to 2. PI, EB, 7-AMD, and OM provided higher CV values, although the 4c to 2 c ratio was still equal to 2. QM, AO, CMA3, and DAPI provided non reproducible and non-stoichiometric nuclear DNA content measurements under the fixation conditions used. The intranuclear and the internuclear SD of the fluorescence intensities describing the fluorescence pattern of the 2c hepatocytes proved to vary according to both the basepair specificity and the binding mode of the fluorochromes. The results reported here argue in favor of an external binding of 7-AMD to DNA and an increased quantum yield of QM when bound to AT-rich DNA. For PI, EB, 7-AMD, and OM, the measured DNA content increased with the fluorescence distribution heterogeneity. This correlation was not observed with other fluorochromes and is suggested to result from decreased fluorochrome accessibility to DNA when the chromatin is condensed. This study demonstrates that under conditions that preserve chromatin organization, only HO for AT-rich DNA and MA for GC-rich DNA can be used, alone or in combination, to measure nuclear DNA content. With other fluorochromes, either the measured DNA content or the chromatin pattern is assessed in suboptimal conditions when fluorescent image cytometry is used. PMID- 1431065 TI - A new acrylic resin formulation: a useful tool for histological, ultrastructural, and immunocytochemical investigations. AB - We describe a new formulation for a hydrophilic resin, mostly composed of glycol methacrylate and hydroxypropyl methacrylate and here referred to as bioacryl, that allows the performance of morphological and immunohistochemical investigations at both light and electron microscopic levels. Immunolocalizations performed on bioacryl-embedded tissues are characterized by high specificity with virtually absent background staining. Finally, the new resin yields satisfactory fine-structural preservation, resulting in ultrastructural images of better quality than those obtained with Lowicryl K4M. PMID- 1431066 TI - Liver metallothionein in the lacrimal gland. PMID- 1431067 TI - Localization of heparan sulfate proteoglycan in basement membranes. PMID- 1431068 TI - Lesbian erotics: the utopian trope of Donne's "Sapho to Philaenis". AB - Famous for its self-assertive masculinity, John Donne's love poetry nonetheless includes a verse elegy which stands alone not only in his work but also in the entire literary production of the Renaissance for its celebration and defense of a passionate lesbian relation binding the two women of its title. No editorial grounds exist for denying Donne's authorship of "Sapho to Philaenis"; rather the interpretive task is to reconstitute the poem's significance in period terms. The task is complicated by Donne's penchant for flouting literary and social convention as he successively overturns Ovid's influential portrayal of Sappho as an aging voluptuary reclaimed for heterosexuality, the virulent homophobia of Renaissance humanists, and the coy idealizations and transient evocation given to lesbian affectivity by the very few Renaissance writers (including Shakespeare) who touched on the subject at all. When "Sapho to Philaenis" is set in the context of Donne's other love elegies in verse as productions by a young intellectual moving in sophisticated London circles and writing for a coterie audience, lesbianism looks like a master trope for positively resolving a dilemma that confounded Montaigne and many other authors of the age. Could the perfections of love and friendship be united in a relation of equality between two persons? Gender hierarchy and separate socialization precluded a heterosexual construction of any such equality in the Renaissance, and the greater opprobrium cast on male homosexuality in this era must have influenced Donne's decision to figure his equal lovers and friends as a lesbian couple. Yet the disclosive power of "Sapho to Philaenis" goes far beyond the entailments of a specific choice of poetic representation. Donne really undertakes to imagine the pleasures, sustenance, and ideological implications by which lesbianism, as a mode of loving and being, resists patriarchal disposition and diminution of women. Donne anticipates the advances of twentieth-century feminists (Colette, Kofman, Irigaray) as he poetically articulates possibilities and knowledge that were otherwise denied expression by Renaissance culture and its exponents. PMID- 1431069 TI - Sodomy and kingcraft in Urania and Antony and Cleopatra. AB - Despite his description of sodomy as a horrible crime that a king is "bound in conscience neuer to forgiue," James I pursued the affections of a string of young and handsome "favourites" on whom he lavished gifts, titles, and power. Relying on the evidence of the King's own letters and frank comments from his Puritan critics, most historians assume that his relations with some of these men were sexual. The King's friendship with Robert Carr (who was later made Earl of Somerset), coupled with his estrangement from Queen Anne, may have been an inspiration for at least two literary accounts of kingship confounded by sex: Lady Mary Wroth's Urania (1621) and Shakespeare's Antony and Cleopatra (1608). Wroth describes a duke who is made politically vulnerable by his love for a young man that leaves him "issue-les." The rise and fall of this disloyal companion closely resembles that of Somerset and would seem to indicate Wroth's belief that the King's relationship with the Earl was sexual. Antony and Cleopatra is in many ways a reflection of Jacobean court extravagance and decadence. Cleopatra, despite her sex, seems to fill the same role in political and sexual scandal as did Somerset; and Antony's vacillation between pleasure and duty recalls a certain Renaissance discourse on sodomy and "kingcraft". PMID- 1431070 TI - Not since Sappho: the erotic in poems of Katherine Philips and Aphra Behn. AB - The presentation of sexuality in poetry may be masked by the use of conventional literary devices that obscure as well as reveal the poems' erotic content. Traditional readings of Katherine Philips' and Aphra Behn's poetry have ignored or denied the lesbian aspects of their verse by dismissing them as asexual representations of well-known literary conventions. This paper argues for a recognition of the ways in which these poetic conventions present a complex and sophisticated lesbian sexuality and also comment on other taboo aspects of human sexual relations. PMID- 1431071 TI - Seeing sodomy: Fanny Hill's blinding vision. AB - One of the oddest and most erotic moments in Cleland's Fanny Hill occurs when Fanny is knocked "senseless" by a voyeuristic vision of two young men having anal intercourse. This sodomitical passage demonstrates a dominant culture's strong phobic attraction to a socially peripheral Other against which it defines itself. The passage also represents two types of transgression. On one level, it records an inversion of sex, gender, and class paradigms that structure bourgeois subjectivity. On another level, the passage also transgresses signification itself, exploding as well as inverting those paradigms, in a movement that recalls Barthes's distinction between the coded "studium" of the pornographic and the uncoded "punctum" of the erotic. This transgressive exemption from meaning might well be read, in a Barthesian sense, as true sexual enfranchisement in that, for Barthes, the liberation of sexuality requires the release of sexuality from meaning, and from transgression as meaning. PMID- 1431072 TI - The sodomitical muse: Fanny Hill and the rhetoric of crossdressing. AB - Cleland's Fanny Hill, banned for centuries largely as a result of a passage depicting male sodomy, has been the focus of several critical approaches since it was republished in the United States in 1963. Critical readings by Nancy K. Miller and Randolph Trumbach in particular indicate that Fanny's persona itself is a "drag" act. While asserting this, no critic has traced the textual complexity of this persona, which is apparent in Cleland's use of figurative language and is accessible through close reading only. PMID- 1431073 TI - "The voice of nature" in Gray's Elegy. AB - Thomas Gray's "Elegy Written in a Country Churchyard" commemorates a problematic sexuality that traditional readings of the poem's "melancholy" usually ignore. By reconsidering the poem in light of theories of abjection, this essay uncovers the powerful poetic expression of a sexuality at odds with mid-century culture and shows how the poet's awareness of his own homosexuality shaped the familiar features of the most popular poem of the eighteenth century. PMID- 1431074 TI - Tradition and the individual sodomite: Barnfield, Shakespeare, and subjective desire. AB - This article compares Shakespeare's sonnets with those written by Richard Barnfield in order to examine the possibility of homoerotic subjectivity in early Renaissance England. Social constructionist debates about sexual subjectivity have convincingly argued that "the homosexual"--the person defined by homosexuality--did not exist before the Enlightenment. The sequences of Shakespeare and Barnfield, both of which deal with homoerotic desire, suggest that homoerotic desire could indeed play a role in defining the individuated subject prior to the Enlightenment. However, the ways in which they use homoeroticism also suggest that subjectivity was defined in radically different ways during the period. PMID- 1431075 TI - Body, costume, and desire in Christopher Marlowe. AB - All the desired youths in Marlowe come clothed in favors, the tokens of older and richer men's yearning. These bribes and rewards, often feminine or effeminate ornaments, not only beautify the already gorgeous bodies of young men, but also label and augment their value and their power. The moment of virility's blooming, in adolescence, is seen as a time when boys can negotiate favorable terms of entry into the realms of manhood by the seductive use of their glamor. For their part, desirous men are distracted from the affairs and cares of state by their nostalgic encounters with girlish boys, at worst, to the extent that their own patriarchal power is compromised by sodomitic dalliance. Marlowe's involvement in these plots is iterative and committed. PMID- 1431076 TI - Verse letters to T.W. from John Donne: "By you my love is sent". AB - Relying on an audience of one for their impact, the verse letters of John Donne are closer to autobiography than anything else in his poetry. Among the most tender of these lyrics are the verse letters written to a young man named Thomas Woodward, whose older brother was one of Donne's closest friends. Using sexual metaphors, the poems reflect a homoerotic undercurrent and demonstrate affection that most readers of Donne associate only with his heterosexual love poems. PMID- 1431077 TI - "Masculine love," Renaissance writing, and the "new invention" of homosexuality. AB - Contrary to the dominant claim in gay studies now that homosexuality is a relatively new historical "invention," the Renaissance had a definite recognition of a distinct homosexuality, acknowledged at least by those who were willing to face and discuss the subject frankly. A key example of that awareness is the earlier term "masculine love," which seems to have been particularly prominent in the Renaissance as a language for a male homosexual orientation. Significant differences have clearly occurred in the homosexual situation over time, and homosexuality can never be discussed totally independent of historical and social conditions, but the "new-inventionism" currently prevailing in gay studies has serious problems of concept and method and needs careful examining. PMID- 1431078 TI - Femme on the streets, butch in the sheets? Lesbian sex-roles, dyadic adjustment, and sexual satisfaction. AB - Recent research suggests that butch-femme role playing in lesbian couples has diminished and been replaced with androgynous attitudes and behaviors. Are lesbians, however, able to maintain an androgynous approach when it comes to lovemaking? Or does the bedroom give way to the powerful influence of traditional gender-based norms for sexual behavior? What implications does the choice of sex roles have for relationship and sexual satisfaction in lesbian couples? The present study of 111 lesbians explores the relationship between sex-role self perceptions, sexual satisfaction, and sexual fulfillment. Findings indicate that lesbians perceive themselves as significantly more feminine when they are interacting sexually than their overall or global sex-role perception. Furthermore, lesbians who view themselves as either androgynous or feminine in a sexual context had the highest level of sexual satisfaction and dyadic adjustment among all four sex-role groups. PMID- 1431079 TI - Freud and sexual reorientation therapy. AB - Contrary to certain psychoanalytic interpretations, Freud himself generally resisted the possibility or desirability of sexual reorientation therapy. Yet his understanding of the origins and nature of homoeroticism does not suggest that conversion therapy is impossible. Although he did not believe homoeroticism to be an inherent impediment to human accomplishment and fulfillment neither did he see it as having the full value of heteroeroticism. For these reasons he did not altogether rule out the desirability or possibility of conversion therapy for some individuals even if he did not believe that it could be psychoanalysis alone that could redirect sexual orientation. PMID- 1431080 TI - Lesbianism and choice. AB - Why does it matter whether a woman can choose whether to be lesbian? I argue by illustration that, first of all, it does make good sense to see the option to be lesbian as genuine for women in a fairly common sort of circumstance; that recognizing the genuineness of this option, however, does not impute to such women major control over their lives; that choosing to be lesbian may actually narrow rather than expand one's present options; and that nevertheless it is important to acknowledge such choices for their potentialities, in community, to change the meaning of "lesbian" in liberatory ways. PMID- 1431081 TI - The gay pediatrician: a report. AB - Since no articles in the medical literature could be found dealing with the subject of the gay pediatrician, a complete bibliographic search was conducted in order to find information about gay health professionals. Using both manual and computerized methods of access to information in many data bases, much pertinent material was found. Reports were accessed which demonstrated that gay pediatricians most certainly exist and that, in addition to their standard role in pediatric and adolescent medicine, they have special and unique contributions to make to the care of our nation's 2.9 million gay youth. Gay pediatricians need to be accepted as valuable professionals by peers and by society. Whenever possible, gay pediatricians need to act as role models to our gay youth. Pediatricians who happen to be gay have much to contribute to medicine. PMID- 1431082 TI - Attitudes toward minorities: a comparison of homosexuals and the general population. AB - As a prelude to a media campaign to improve the public image of gays, a gay rights organization in Columbus, Ohio, constructed a questionnaire to assess perceptions of and attitudes toward gays and various other minority groups including blacks, Jews, women, communists, and recovering alcoholics. The questionnaire was administered to two samples in the central Ohio area: a sample of the greater Columbus population at large, and a sample of gays and lesbians. This article reports on the comparative findings from these two samples. PMID- 1431083 TI - Passing and social support among gay men. AB - One hundred sixty-six gay men responded to a questionnaire survey which asked them to describe their social networks and the extent to which they 'passed' (were assumed to be heterosexual) among network members. Most gay men were known as gay to most members of their networks; however, friends, siblings and persons close to respondents were more likely to be aware of their homosexuality than co workers, parents, and more distant relatives. Gay men were more satisfied with social support available from those who knew of their sexual orientation. The author concludes that passing has important and complex effects on the social networks of gay men. PMID- 1431084 TI - Adult responses to child behavior and attitudes toward fathering: gay and nongay fathers. AB - This study examines gay and nongay fathers' responses to instruments measuring parenting style and orientation to the fathering role. Fifty-three respondents (24 gay and 29 nongay fathers) completed two surveys, and responses to each were analyzed. Both groups of fathers were found to have a developmental orientation toward their role as fathers, and no discernible parenting style could be found to distinguish one group from the other. Thus, gay and nongay fathers were found to be more similar than different with regard to parenting styles and attitudes toward fathering. This finding supports previous work (Bigner & Jacobsen, 1989a, 1989b) and expands the available knowledge based on the parenting styles of homosexual parents. PMID- 1431085 TI - Public endorsement of restrictions on three aspects of free expression by homosexuals: socio-demographic and trends analysis 1973-1988. AB - The willingness of the public to endorse proposals to remove gay-positive books from library shelves, to dismiss college teachers who are homosexuals, and to prohibit public speaking by homosexuals was examined. A socio-demographic analysis aggregating the entire period 1973 through 1988, and an analysis of trends over the period, were undertaken using data from the General Social Surveys. Responses to survey questions concerning homosexuals were compared with responses to similar questions concerning other unpopular groups, and to questions which called upon the respondent to make a moral judgment concerning homosexual relations. A significant decline over the period was found in the public's willingness to endorse restrictions on homosexuals, and on each of the other unpopular groups used for comparison. Level of education appeared to be a strong indicator of a more tolerant attitude. Paradoxically, negative moral attitudes toward homosexual relations did not decline. Bias in the wording of the General Social Surveys' questions concerning the moral dimension of homosexuality may have distorted these results, however. The public's moral attitude toward homosexual behavior does appear to be quite labile from year to year, suggesting that concerted efforts to educate the public on this subject can have an important and rapid effect. PMID- 1431086 TI - "Man's words" and manly comradeship: language, politics, and homosexuality in Walt Whitman's works. AB - Critical assessments of Walt Whitman's works either emphasize his sexual themes while ignoring his political ideas or they focus on the poet's politics but ignore his poetics of corporeality. Recent studies that do discuss both politics and sexuality in Whitman's works do not devote much attention if any to the poet's theory of language as it appears in his An American Primer. This essay explores the complex intersections among sexuality, politics, and language in Whitman's works, illustrating how the poet consistently correlated his linguistic, sexual, and political metaphors, constantly relating the health and the sexual potency of the male body with the power of language, the efficacy of literature, and the strength of the states in the United States. Underlying these multiple metaphors and poetic intentions is the poet's homosexual vision. It constitutes the basis of his linguistic theory, his hope of an ideal democratic union, and his plea for sexual equality. To Whitman, America needed male-to-male friendships to free it from materialistic vulgarities and to ensure its perpetuation. PMID- 1431087 TI - Visions and revisions of reality: reflections on sex, sexuality, gender, and gender variance. AB - Varying perceptions of gender, sex, and sexuality are investigated, using several examples, from the Pokot of East Africa to the Tewa Indians in New Mexico. The role that labels play in the acquisition of gender identity is also explored; and the influence of Cartesian dualism is challenged, suggesting a need to expand Euro-American conceptions of gender. PMID- 1431088 TI - The relationship of instrumentality and expressivity to sexual orientation in women. AB - The study reported here investigated the relationship between Instrumentality (I) and Expressivity (E) (two personality variables related to sex roles), sexual orientation, occupational level and marital status. The hypothesis was that women high in I and low in E may find traditional heterosexual relationships to be in conflict with their personality traits, and that a lesbian choice may offer a way of life more in keeping with such traits. The study used a sample of 159 women, and found that neither I nor E alone, nor I x E, could predict sexual orientation. A weak relationship was found between I and housewifery, such that women who were married with children and did not have a job outside the home tend to score lower on I. Expressivity bore no relationship to any of the variables. Women who were high on I and low on E were not more likely to be lesbian. The study concludes that there is no relationship between I, E, and sexual orientation; also that it is inappropriate to use housewives as a heterosexual comparison group for lesbian women. PMID- 1431089 TI - Are gay men artistic? A review of the literature. AB - There is a popular perception that gay men are artistic. Although art historians and others have documented the substantial contribution to art made by gay men, the existence of a unique gay sensibility remains controversial. Mental health practitioners who work with gay men have addressed aesthetic sensibility in the childhood of gay men, but not the role of art in their adult lives. A literature search on the relationship between homosexuality and artistic ability and/or achievement shows that there is little scientific data addressing this subject. Reasons for the lack of literature as well as suggestions for future research are offered. PMID- 1431090 TI - Researcher-participant relationships in journal reports on gay men and lesbian women. AB - To assess the ethical nature of research relationships between investigators and gay and lesbian participants we reviewed 351 reports on homosexuality in three major and 75 miscellaneous journals from 1974 to 1988. We found that authors rarely involved participants beyond the role of providing data, generally did not report conditions of consent, rarely reported feedback, and almost never indicated using data to promote social action. In addition, authors typically relied on the term "subjects" and on a depersonalized, decontextualized writing style. There were some differences among journals, over time, and among authors' disciplines. Male authors tended to study men exclusively, whereas female authors' relation to participants' gender was more varied. Believing that research with gay men and lesbian women should not detract from their emancipation, we offer some recommendations for research practice and report writing which are designed to better protect research participants and to produce more valid knowledge. PMID- 1431091 TI - Genetic nomenclature for loci controlling surface antigens of mouse hemopoietic cells. PMID- 1431092 TI - Tolerance to host minor histocompatibility antigens after allogenic bone marrow transplantation. Specific donor-host unresponsiveness is maintained by peripheral tolerizing cells. AB - The development of graft-host tolerance after allogeneic bone marrow (BM) transplantation is more demanding than the acquisition of self-tolerance because both donor-derived mature T cells and immature thymocytes encounter host Ag. The mechanism involved in tolerization of mature T cells, contained in unmanipulated BM, remains undefined. In previous experiments, we showed in vivo unresponsiveness to host minor histocompatibility Ag (MiHA) in immunocompetent chimeras obtained after MiHA-incompatible BM transplantation. In this study, we wanted to determine: first, what was the specificity of this graft-host unresponsiveness, and second, whether peripheral cells were involved in tolerization? LP recipients were irradiated (9, 5 Gy), injected with 10(7) undepleted BM cells from B10 donors and studied 100 to 150 days later. (B10-->LP) chimeras were immunized in vivo and restimulated in vitro with cells displaying one or multiple incompatible MiHA. In bulk culture experiments, chimeras demonstrated specific CTL unresponsiveness to host MiHA but responded normally to third party MiHA. In limiting dilution analysis conditions, chimeras showed a profound deficit, but not a complete absence of anti-host CTL precursor. Studies with congenic stimulators/targets showed that graft-host tolerance was induced against both immunodominant (e.g., H-3.2) and nonimmunodominant (e.g., H-8.2) MiHA although at the CTL precursor level, it was more complete against the former. Furthermore, chimera spleen cells inhibited the generation of CTL activity against host- and donor-type MiHA but not against third party Ag. This specific suppressor activity was not T cell dependent, and was mediated by radiosensitive cells that are not found in freshly explanted organs from normal mice. Taken together, our results suggest that peripheral tolerization can be a remarkably efficient process to maintain tolerance to MiHA after BM transplantation. Thus, peripheral tolerizing mechanisms may contribute not only to the induction of tolerance to Mls superantigens or to the product of transgenes (if expressed at high levels) but also to a wide array of MiHA. PMID- 1431094 TI - Effect of class I MHC binding peptides on recognition by natural killer cells. AB - NK cells can recognize and destroy a broad range of cells, including many tumor cells and virally infected cells, yet spare most normal cells. Identification of the target structure recognized by these cells has proved elusive. An attractive hypothesis is that, unlike B cells and T cells that recognize a specific foreign marker, NK cells respond to the absence of a "self" marker. Class I MHC molecules have been implicated as the self markers whose absence can trigger lysis. We show here that normal cells are lysed on incubation with IL-2-activated NK cells if peptides that can bind to the class I MHC molecules of the normal cells are also included in the assay, and speculate that this binding is somehow removing a self marker that normally protects a cell from lysis. NK cells were derived from splenocytes of young (5 to 8 wk old) athymic nude BALB/c (H-2d) or nude C57Bl/6 (H-2b) mice incubated with 1000 U/ml rIL-2, and target cells were derived from splenocytes of normal BALB/c or C57Bl/6 mice incubated with Con A. Peptides were from xenogeneic, viral, self, and mutated self protein sequences and included sequences specific for Kd, Kb, Db, and Ld. All peptides increased lysability of those targets to which they could bind. PMID- 1431093 TI - Selective association between MHC class I-restricted T cell receptors, CDS, and activated tyrosine kinases on thymocytes undergoing positive selection. AB - Developing T cells undergo distinct selection processes that determine the TCR repertoire. Positive selection involves the differentiation of immature thymocytes capable of recognizing antigens complexed with self-MHC molecules to mature T cells. Besides the central role of TCR engagement by MHC in triggering selection; the interaction of CD8 and CD4 with MHC class I and class II, respectively; is thought to be important in regulating the selection process. To study potential mechanisms involved in positive selection of CD8+ cells, we have analyzed mice expressing a unique transgenic TCR. The transgenic receptor recognizes the HY male Ag in the context of the MHC class I molecule, H2-Db. We describe that CD8 and the TCR are selectively associated in thymocytes of mice expressing the restricting MHC, but not in thymocytes of mice expressing a nonrestricting MHC. pp56lck and pp59fyn, the tyrosine kinases associated with CD8 and TCR, respectively, were found to be present in this complex in an activated form. No comparable TCR-CD4 complex formation was found in thymuses undergoing positive selection to CD8+ cells. The formation of a multimolecular complex between CD8 and TCR, in which pp56lck and pp59fyn are activated, may initiate specific signaling programs involved in the maturation of CD8+ cells. PMID- 1431095 TI - Induction of apoptosis by monoclonal antibody anti-APO-1 class switch variants is dependent on cross-linking of APO-1 cell surface antigens. AB - Apoptosis, programmed cell death, was previously shown to be induced by the mAb anti-APO-1 (IgG3, kappa) by binding to the APO-1 cell surface Ag, a new member of the nerve growth factor/TNF receptor superfamily. To investigate the role of the Ig H chain Fc regions we compared induction of apoptosis by the original mAb IgG3 anti-APO-1 with anti-APO-1 F(ab')2 fragments and different anti-APO-1 isotypes (IgG1, IgG2b, IgG2a, and IgA) isolated by sequential sublining. We found that IgG3 was the most active isotype; IgG1, IgG2a, and IgA showed intermediate activity, and IgG2b and F(ab')2 were inactive. Cytotoxic activity of the inactive or less active antibody preparations was fully reconstituted by protein A, anti mouse Ig, or anti-mouse Ig F(ab')2, respectively. Thus, APO-1-mediated induction of apoptosis was dependent on efficient cross-linking of APO-1 cell surface Ag, indirectly augmented by anti-APO-1 Fc-Fc self-aggregation. Because of their different in vitro activity we selected IgG3-, IgG2b-, and IgA anti-APO-1 to test their antitumor activity against solid human B lymphoblastoid tumors in SCID mice. The isotypes showed a different serum half-life (IgG3: 9.2-10.4 days, IgG2b: 1.9-2.6 days, and IgA: 14.1-29.2 h) and a different initial tumor localization 4 h after i.p. injection (IgG3 around the blood vessels, IgG2b homogeneously, and IgA heterogeneously distributed in the tumor). All antibody preparations induced tumor regression by induction of apoptosis, even IgG2b anti APO-1 inactive in vitro without cross-linking. The activity of IgA anti-APO-1, which did not mediate complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity indicates that apoptosis may be used as the main if not the only mechanism of induction of tumor regression in vivo. As with in vitro, IgG3 anti-APO-1 was the most effective isotype also in vivo. This result suggests that cross-linking of APO-1 on the tumor cell surface may also be required for tumor regression by apoptosis in vivo. Taken together, our data show that selective targeting of apoptosis to tumors may be an efficient antitumor mechanism. PMID- 1431096 TI - Basement membrane and its components on lymphocyte adhesion, migration, and proliferation. AB - During inflammation and recirculation, lymphocytes migrate into tissues by traversing the capillary endothelium, a process known as extravasation. After crossing the endothelial cells, lymphocytes come into contact with the basement membrane, which is a specialized layer of extracellular matrix containing predominantly laminin, collagen type IV, entactin, and heparan sulfate proteoglycans. In tissue invasion by inflammatory cells and metastatic tumor cells, the basement membrane serves as a substratum for cell adhesion and migration. However, the role of basement membrane in lymphocyte extravasation remains unclear. In this study, we investigated the effect of basement membrane on lymphocyte adhesion, migration, and proliferation, using matrigel as a model for basement membrane. We observed that matrigel promotes both lymphocyte adhesion and migration, with entactin primarily responsible for promoting adhesion and laminin for promoting migration. In addition, activation of lymphocytes by anti-CD3 enhances their adhesion and migration on matrigel-coated substratum. We also observed that matrigel inhibits the proliferation of lymphocytes stimulated by Con A. Furthermore, we demonstrated that laminin is the matrigel component responsible for inhibiting lymphocyte proliferation. However, matrigel has no effect on the proliferation of lymphocytes stimulated by LPS. These results suggest that matrigel has different effects on lymphocyte subpopulations. In agreement with the results on proliferation, matrigel also inhibits the production of IL-2 by Con A-stimulated lymphocytes. PMID- 1431097 TI - Regulation of basal tyrosine phosphorylation of the B cell antigen receptor complex by the protein tyrosine phosphatase, CD45. AB - Signal transduction via the B cell AgR complex has recently been shown to be dependent on the activation of one or more protein tyrosine kinases. Similarly, it has been found that signal transduction requires the expression of the protein tyrosine phosphatase CD45. Thus, transduction of a signal after AgR cross-linking must involve the coordinate interaction of these two enzymatic activities. It is therefore logical to hypothesize that the competence of the B cell to respond to ligands that bind the AgR may be dependent on the maintenance of an equilibrium between the tyrosine phosphorylation and dephosphorylation of specific signal transduction components. We have demonstrated in the present study that in resting B cells, the basal level of AgR complex tyrosine phosphorylation is regulated by cellular protein tyrosine phosphatases. Treatment of cells with the protein tyrosine phosphatase inhibitor, Na3VO4, resulted in rapid hyperphosphorylation of the receptor complex. Based on this observation, experiments were designed to examine the role of CD45 in regulation of AgR complex phosphorylation. Treatment of B cells with anti-CD45 mAb alone was found to have no effect on cytoskeletal association of CD45 or on its distribution within the membrane. Addition of a secondary cross-linking reagent, however, induced the association of CD45 with the cytoskeleton and caused capping. Subsequent studies demonstrated that increased tyrosine phosphorylation of the mIg-associated proteins MB-1 and B29 could be induced after incubating cells with anti-CD45 mAb and a secondary cross-linker, but not after the addition of anti CD45 mAb alone. Changes in tyrosine phosphorylation of MB-1 and B29 were found to correlate with the cytoskeletal association of CD45. Interestingly, although cross-linking CD45 induced alterations in its association with the cytoskeleton and in its distribution within the membrane, no significant change in the level of protein tyrosine phosphatase activity could be detected under these conditions. These findings support the possibility that ligand binding to CD45 can induce biochemical and/or physical alterations in the molecule that presumably inhibit its ability to interact with specific substrates in the cell, thereby shifting the established equilibrium between tyrosine-specific phosphorylation and dephosphorylation. PMID- 1431098 TI - Unidirectional, heterologous desensitization of the pertussis toxin receptor by the CD3/TCR complex. AB - Prolonged exposure of many types of receptors to their cognate agonists can lead to a progressive lack of responsiveness. When this occurs after stimulation by the primary agonist for a given receptor it is termed homologous desensitization, and heterologous desensitization when to an agonist binding to a different type of receptor. Pertussis toxin (PTx) is a potent mitogen for human T lymphocytes. We have previously identified the human T cell PTx receptor (PTx-R) as a 43-kDa plasma membrane protein that, when stimulated, leads to the production of the intracellular second messengers, inositol-1,4,5-triphosphate, 1,2-sn diacylglycerol, and elevated cytosolic calcium. The PTx-R appears to require the co-expression of the CD3/TCR complex because mutant cells that lack the AgR, but express the PTx-R, fail to respond to PTx. In this report, we have investigated the relationship between these two receptor systems. Activation of the PTx-R with submaximal concentrations of PTx did not affect the ability of an anti-CD3 antibody combined with rabbit anti-mIg to stimulate increases in intracellular free calcium concentration [Ca2+]i or diacylglycerol in human peripheral blood T cells. However, treatment with soluble anti-CD3 mAb, which lead to only a modest increase in [Ca2+]i, completely inhibited the effect of PTx. The cells were not refractory to further stimulation of the AgR because cross-linking with rabbit anti-mIg resulted in the standard maximal stimulation. This effect could be observed within 1 min of treatment with anti-CD3 mAb, and persisted for at least 1 h. The effect was not caused by production of either diacylglycerol (leading to activation of PK-C) or an increase in [Ca2+]i by anti-CD3 mAb because the effect could not be mimicked by either phorbol esters or a calcium ionophore. Pretreatment of either resting T lymphoblasts or PBL with anti-CD3 mAb also prevented enhanced [3H]TdR incorporation stimulated by PTx. These observations suggest a model in which T cells can regulate amplification of a non-AgR stimulatory pathway by heterologous desensitization. PMID- 1431099 TI - Peripheral T cell receptor gamma delta variable gene repertoire maps to the T cell receptor loci and is influenced by positive selection. AB - Although the mechanisms that determine TCR-alpha beta V gene repertoire are well studied, the genetic influences involved in TCR-gamma delta repertoire development are unclear. Unlike the TCR-gamma delta populations that localize in epithelial tissues, the circulating peripheral TCR-gamma delta V region repertoire is quite diverse. Previous studies have shown that three TCR-gamma chains and at least six TCR-V delta genes are expressed by splenic TCR-gamma delta cells. However, the relative frequency of individual gamma delta subsets among genetically diverse mice has not been determined. Therefore, the repertoire of TCR-gamma delta cells was examined using anti-TCR V region specific mAb against V gamma 2 and V delta 4 on TCR-gamma delta + cells from total splenocytes. We found that there was a strain-specific variation in TCR-gamma delta usage. The frequency of V gamma 2 expression in different strains varied from 54 to 12%, and the frequency of V delta 4 expression in different strains varied from 38 to 10%. However, the level of V delta 4 and V gamma 2 expression for an individual strain was highly consistent from experiment to experiment. F1 analysis between parental strains that differed in relative frequency of either V gamma 2+ or V delta 4+ cells revealed that high expression was genetically dominant, suggesting that positive selection events play a major role in the peripheral gamma delta repertoire. Variations in the levels of V gamma 2+ cells and V delta 4+ cells was not associated with Mls or MHC haplotype. Analysis of recombinant inbred strains revealed that high V delta 4 expression mapped to the TCR-gamma locus, while high V gamma 2 expression was influenced by the TCR-delta locus. Back-cross analysis confirmed that the TCR loci dominantly influenced the level of V delta 4+ cells and V gamma 2+ cells; however, there was clear evidence that multiple genes affect the TCR-gamma delta repertoire. PMID- 1431100 TI - The C/EBP family of transcriptional activators is functionally important for Ig VH promoter activity in vivo and in vitro. AB - We have examined the functional importance of binding sites for C/EBP family members (E sites), in two Ig VH promoters: VH1, a member of the S107 family, and BCL1, a member of the J558 family. Mutation of the E site in the VH1 promoter diminishes transcription in vivo to 59% of wild-type and transcription from the BCL1 promoter in vitro is inhibited to an average of 39% of wild-type by competition with E site oligonucleotides. Purified E site binding proteins from plasmacytoma cells stimulated BCL1 transcription in vitro 2.3-fold. Although five C/EBP family proteins are known which bind the E site, antibody ablation of DNA:protein complexes resolved by electrophoretic mobility shift assays showed that Ig/EBP-1 is the only E site binding protein detectable in early B cell lines; more mature B cells contain Ig/EBP-1 and NF-IL6. We also show by antibody depletion that Ig/EBP-1 activates the BCL1 promoter in vitro. PMID- 1431101 TI - EBV/C3d receptor (CR2) interacts by its intracytoplasmic carboxy-terminal domain and two distinct binding sites with the p53 anti-oncoprotein and the p68 calcium binding protein. AB - EBV/C3d receptor (CR2) interacts with the p53 anti-oncoprotein expressed in the human B lymphoma cells, Raji but not in normal B cells, and with the p68 calcium binding protein, expressed in normal B lymphocytes but not in transformed B lymphocytes. To characterize the CR2 domain interacting with these two intracellular proteins, we synthesized a 34-amino acid peptide, pep34, corresponding to its intracytoplasmic carboxy-terminal domain and analyzed its binding and antigenic properties. Binding of 125I-labeled p53 or 125I-labeled p68 on immobilized pep34 was specific, additive, and totally inhibited by unlabeled p53 or p68, respectively, but not by unlabeled p68 or p53, respectively. Antigenic properties of pep34 were analyzed by immunizing rabbits with particle bound pep34. Polyclonal anti-pep34 Ab carried anti-CR2 specificities that recognized only the intracellular domain of CR2. In addition, anti-pep34 Ab also carried anti-p53 or anti-p68 specificities. Anti-p53 or anti-p68 specificities were not due to putative common structural or conformational antigenic determinants between the pep34 synthetic peptide and the p68 or p53 proteins. These anti-p53 and anti-p68 specificities were identified as anti-idiotypic anti CR2 Ab mimicking either p53 or p68 binding sites of CR2. These data clearly establish that despite its short length, the intracytoplasmic C-terminal tail of CR2 is involved in direct protein-protein interactions with the two intracellular regulatory proteins, p53 and p68. An additional feature of these data is the demonstration that particle-bound pep34 triggered "in vivo" anti-Id Ab restricted to either p53 or p68 specificities. PMID- 1431102 TI - A DNase I-hypersensitive site in the second intron of the murine IL-4 gene defines a mast cell-specific enhancer. AB - IL-4 is a potent immunoregulatory cytokine that exhibits extremely diverse effects on a number of target cells. Although IL-4 was originally described as a T cell-derived product, it is evident that cells of the basophil/mast cell lineage are also an important source of this cytokine. Based on their different tissue distribution, mast cell and T cell-derived IL-4 may have distinct effects on local immune responses. The physiologic production of IL-4 appears to be tightly regulated because most T and mast cells require activation to express significant levels of IL-4. In contrast, a majority of murine transformed mast cell lines constitutively express relatively high levels of IL-4. In this study, transformed mast cell lines were used as models to define cis acting sequences that regulate mast cell IL-4 transcription. Chloramphenicol acetyltransferase reporter gene constructs containing 6.3 kb of 5' IL-4 flanking sequence direct relatively low chloramphenicol acetyltransferase expression in these cells. These results indicated that additional sequences may be important in stimulating transcriptional activity of the IL-4 gene. Using DNAse I hypersensitive site analysis to define other potential IL-4 transcriptional regulatory regions, two sites were identified in the murine IL-4 gene that appear to be unique to IL-4 expressing transformed mast cells. One site defines an intronic sequence that exhibits prototypic enhancer activity in several independently derived transformed mast cell lines. This enhancer is also active in stimulated, non transformed mast cells but not stimulated EL-4 T cells. Taken together, these data indicate that the IL-4 intronic sequence contains a mast cell specific enhancer that plays an essential role in the unregulated expression of IL-4 in transformed mast cells and may also be important in the inducible expression of IL-4 in normal mast cells. PMID- 1431103 TI - Molecular cloning of the murine IL-1 beta converting enzyme cDNA. AB - IL-1 beta is a potent modulator of immune and inflammatory responses. Murine IL-1 beta is initially synthesized as an inactive 33-kDa pro-molecule that is activated by proteolytic cleavage between Asp-117 and Val-118 to generate the 17 kDa mature IL-1 beta protein. This cleavage is catalyzed by a specific protease that has been designated the IL-1 beta converting enzyme (or IL-1 beta convertase). We have used a human IL-1 beta convertase cDNA to isolate murine convertase cDNA from a WEHI-3 library. These cDNA predicted that the murine convertase is a 402-residue protein. Overall, the murine convertase showed 71% nucleotide and 62% predicted amino acid sequence identity with the human convertase. Southern blot analysis of interspecific backcross mice indicated that the murine IL-1 beta convertase is encoded by a single copy gene located on murine chromosome 9. The murine convertase showed broad constitutive expression, being detected in mononuclear phagocyte and T lymphocyte cell lines as well as in spleen, heart, brain, and adrenal glands. The expression of the murine convertase in mononuclear phagocytes was up-regulated by treatment with LPS or rIFN-gamma. These studies establish that the IL-1 beta convertase is an evolutionarily conserved, widely expressed enzyme that can be regulated at a pretranslational level. PMID- 1431104 TI - Patterns of antibody specificity during the BALB/c immune response to hen eggwhite lysozyme. AB - We tested 49 BALB/c antilysozyme mAb from seven intervals during the immune response to lysozyme for patterns of specificity and avidity. We found that the antibody epitopes in composite covered at least 80% of the lysozyme surface, and their patterns of overlap suggest a continuum of potential antibody epitopes. Previously observed regional specificities, which emerged at different times in the immune response, were more discretely defined in late response antibodies, when the majority of mAb could be assigned to one of three functionally nonoverlapping complementation groups. The area covered by each antigenic region may be greater than an individual epitope, and may include multiple epitopes that overlap structurally and functionally to varying degrees. Connectivity between antigenic regions was seen in interactions among early and late stage antibodies, and among secondary stage mAb, but not among tertiary stage mAb from hyperimmunized mice. Patterns of overlap of early and late response antibodies suggest that the organization of antibody specificities change during the progression from primary to secondary to tertiary response. Over the same period in the response, the average relative avidity of IgG1 kappa mAb did not increase, suggesting that "affinity maturation" of serum antibodies reflects an increase in the number and diversity of antibodies, rather than an overall increase in the avidity of individual antibodies. PMID- 1431105 TI - Molecular characterization of the WC1 antigen expressed specifically on bovine CD4-CD8- gamma delta T lymphocytes. AB - Although gamma delta T lymphocytes were identified several years ago, the functional importance of these cells remains to be established. gamma delta T cells of ruminants are unique in two respects. First, they are present at much higher levels compared to man and rodents. Second, ruminant CD4-CD8- gamma delta T cells uniquely express a 220 kD surface Ag recognized by a panel of mAb, recently clustered as WC1. WC1 has been most extensively studied in sheep with the use of the mAb T19. Here, we report on the isolation of a full length cDNA clone, encoding the WC1 Ag, from a COS cell cDNA expression library prepared from a bovine gamma delta T cell line. The protein encoded by the pWC1 cDNA clone was reactive with the bovine mAb CC15 and IL.A29, and with T19. The cDNA clone consisted of 4475 bp and contained a single long open reading frame of 1436 amino acids. The pWC1 cDNA clone encoded a type 1 integral membrane protein with an extracellular domain consisting of 11 scavenger receptor cysteine-rich-repeats with homology to CD5 and CD6. Southern blotting suggested that the bovine genome contained multiple sequences highly related to the isolated WC1 cDNA. Furthermore, WC1-like sequences were present in the genomes of all mammals tested including mouse and man. The molecular characterization of the WC1 Ag as reported here provides a starting point for the definition of its role in gamma delta T cell biology. PMID- 1431107 TI - Retinoic acids inhibit activation-induced apoptosis in T cell hybridomas and thymocytes. AB - Apoptosis is induced in immature thymocytes and T cell hybridomas upon stimulation via the TCR/CD3 complex. This phenomenon appears to be related to negative selection of T cell clones in the thymus. In T cell hybridomas, it has been shown that glucocorticoids inhibit TCR/CD3-mediated apoptosis, whereas glucocorticoids alone induce apoptosis. All-trans-retinoic acid (RA) at 0.1 to 10 microM also inhibited TCR/CD3-mediated apoptosis assessed by DNA fragmentation and cytolysis, but RA alone hardly induced apoptosis. RA enhanced the effects of glucocorticoids to induce apoptosis and to inhibit TCR/CD3-mediated apoptosis. TCR/CD3-mediated stimulation can be mimicked by the combination of ionomycin, a calcium ionophore, and PMA, an activator of protein kinase C, and the combination induced DNA fragmentation was also inhibited by RA. RA, however, failed to inhibit the combination-induced increase in intracellular Ca2+ concentration or the combination-induced translocation of protein kinase C from the cytosolic fraction to the particulate fraction. Time course studies of RA addition into the culture indicated that a 3- to 6-h delay in the addition of RA did not reduce its inhibitory effect on anti-CD3-induced DNA fragmentation. These results suggest that RA interferes with the apoptotic process at some point after its initiation stage. It has been suggested that negative selection involves not only TCR/CD3 mediated signals but also LFA-1-mediated signals. RA at 0.01 to 1 microM significantly inhibited the induction of thymocyte apoptosis by co-immobilized mAb to CD3 and LFA-1 molecules. RA by itself hardly induced apoptosis, but enhanced glucocorticoid-induced apoptosis. The results suggest that thymic selection might be influenced by RA at near-physiologic concentrations. The receptors of glucocorticoids and RA belong to the erbA oncogene-related steroid hormone receptor superfamily. Thyroid hormones and 1 alpha,25-dihydroxy vitamin D3, whose receptors also belong to the superfamily, failed to modulate apoptosis in both T cell hybridomas and thymocytes. PMID- 1431106 TI - Tumor necrosis factor-alpha-dependent production of reactive nitrogen intermediates mediates IFN-gamma plus IL-2-induced murine macrophage tumoricidal activity. AB - We have previously established that IFN-gamma plus IL-2 induces murine macrophage tumoricidal activity. The purpose of this study was to identify the effector molecules that account for the IFN-gamma plus IL-2-induced macrophage cytotoxicity against P815 mastocytoma cells. ANA-1 macrophages and normal thioglycollate-elicited mouse peritoneal macrophages produced little or no detectable nitrite (NO2-) after incubation with IFN-gamma alone or IL-2 alone; however, IL-2 synergized with IFN-gamma for the production of NO2-. IFN-gamma plus IL-2 did not induce NO2- production or tumoricidal activity in ANA-1 macrophages that were cultured in medium devoid of L-arginine or in ANA-1 macrophages that were incubated with NG-monomethyl-L-arginine. As observed previously with ANA-1 macrophage tumoricidal activity, IL-4 inhibited IFN-gamma plus IL-2-induced, but not IFN-gamma plus LPS-induced, NO2- production. IL-4 also selectively decreased the ability of IFN-gamma and/or IL-2 to augment TNF-alpha mRNA expression in ANA-1 macrophages. Lastly, incubation of ANA-1 macrophages with anti-TNF mAb selectively inhibited the ability of IFN-gamma plus IL-2 to induce NO2- production and tumoricidal activity. These results indicate that IFN gamma plus IL-2-induced tumoricidal activity is dependent upon the metabolism of L-arginine to reactive nitrogen intermediates, and they establish a role for TNF alpha as a required intermediate for IL-2-dependent NO2- production and tumoricidal activity. PMID- 1431108 TI - Role of IL-6, IL-2, and IL-4 in the in vitro induction of cytotoxic T cells. AB - The mode of IL-6-induced differentiation of Con A-stimulated CD4-CD8+ CTL-P was examined. Through application of neutralizing anti-IL-6, anti-IL-2, and anti-IL-4 mAb it was shown that IL-6 is an "early acting" factor for development of accessory cell-depleted thymocytes. IL-2 and IL-4 are obligatory "late acting" factors for this process. In accordance IL-4, but not IL-6, induced active CTL from CD4-CD8+ CTL-P. The increase of CD4-CD8+ CTL originates at least partially from CD4+CD8+ cells differentiating to active CTL in vitro. CTL development was paralleled by an increase in CD4-CD8+ cells and by a distinct increase in [3H]TdR uptake on day 2 of cultivation. Our data suggest that IL-6 induces Th cells to produce IL-2 and IL-4, the mediators for final differentiation of CD4-CD8+ cells. PMID- 1431109 TI - Antibodies and reactive T cells against the malaria heat-shock protein Pf72/Hsp70 1 and derived peptides in individuals continuously exposed to Plasmodium falciparum. AB - Pf72/Hsp70-1, a heat-shock protein of m.w. 72 kDa from Plasmodium falciparum is one of the Ag of interest to be included in a polyvalent vaccine against malaria. It is one of the major immunogens present in a fraction of purified blood stage parasites that elicited protection against experimental infection of Saimiri monkeys with blood stages of P. falciparum. It is present at all blood stages and one of its B cell epitopes is also detected on the surface of the infected hepatocyte. Moreover, Pf72 appears to be well conserved among different isolates of P. falciparum. We have examined the immune response against Pf72/Hsp70-1 in individuals from different age groups living in a holoendemic area (West Africa). The immune response against the native Ag (purified from schizonts and called Pf/Hsp70) was analyzed both at the humoral level by ELISA and at the cellular level by assessing in vitro proliferation and IFN-gamma production of PBMC. Of the individuals studied 52% had a statistically significant level of anti Pf/Hsp70 antibodies as compared with unexposed individuals. These positive individuals showed a heterogeneous distribution because significant levels of antibodies were found in 70% of the adults but in only 26% of the children. The presence of Pf/Hsp70-specific reactive T cells in the blood was detected in 32% of the individuals. The total anti-Pf/Hsp70 antibody level (IgG+IgM) appeared strongly age related and correlated positively with parasite exposure, whereas the T cell response failed to correlate either with the antibody level or with age. Moreover, PBMC of donors responded to the Pf/Hsp70 in a dissociated way, namely, by either T cell proliferation or IFN-gamma production. Ten synthetic peptides based on sequences found in the C-terminal part of Pf72/Hsp70-1 were further tested as potential T cell epitopes. The proliferative response of PBMC from individuals continuously exposed to the parasite showed that three peptides more frequently trigger significant T cell proliferation (in 21% to 27% of the individuals) and three others less frequently (10%). None of these peptides allowed detection of reactive T cells in PBMC of Europeans with no previous exposure to malaria. Some of the stimulating peptides are highly similar to human heat-shock Hsc and Hsp70 with large stretches of identical amino acids.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1431110 TI - Selective expression of a major allergen and cytotoxin, Asp f I, in Aspergillus fumigatus. Implications for the immunopathogenesis of Aspergillus-related diseases. AB - Asp f I is a major 18-kDa Aspergillus fumigatus allergen and a member of the mitogillin family of cytotoxins. The nucleotide sequence of the Asp f I gene was determined by sequencing polymerase chain reaction products amplified from A. fumigatus spore DNA. The entire 678-bp DNA includes an 81-bp leader sequence, preceding the N-terminal alanine codon, a 52-bp intron, and a 444-bp open reading frame, encoding a 149-amino acid protein (M(r) 16,899), which is 99% homologous to mitogillin from Aspergillus restrictus. A mAb-based ELISA was used to compare Asp f I levels in spores, mycelia, and culture filtrate, and to determine the kinetics of allergen production. Disrupted hyphae or spore extracts had a 1000 fold lower level of Asp f I than culture filtrate, suggesting that germination of spores and growth of the fungus are essential for allergen production. Asp f I levels in A. fumigatus and A. restrictus peaked at day 3 (0.87 to 12.1 micrograms/ml), however, the allergen was not detected in Aspergillus flavus, Aspergillus niger, Aspergillus terreus, and Aspergillus nidulans cultures (< 1.5 ng/ml) on either days 3 or 8. Northern analysis confirmed that Asp f I mRNA was detected only in A. fumigatus and A. restrictus, but not in the other four Aspergillus spp. Asp f I-specific DNA was generated after polymerase chain reaction amplification of genomic mycelial DNA obtained from A. fumigatus and A. restrictus, but not from the other Aspergillus spp. The results show that Asp f I is selectively expressed in A. fumigatus, and suggest that this cytotoxin could be a specific virulence factor for A. fumigatus. PMID- 1431111 TI - Role of P2z purinergic receptors in ATP-mediated killing of tumor necrosis factor (TNF)-sensitive and TNF-resistant L929 fibroblasts. AB - Two closely related cell lines were characterized in their responses to extracellular ATP (ATPo): the fibroblast cell line L929 and a TNF-resistant variant L929/R. Both lines showed ATPo-activated increases in intracellular Ca2+, inward current, and sustained depolarization of the plasma membrane, cell responses compatible with activation of purinergic receptors of the P2y, P2x, or P2z subtype; however, only the L929/R variant was susceptible to ATPo-dependent early permeabilization of the plasma membrane to hydrophilic solutes of M(r) below 900, a response uniquely caused by the activation of P2z receptors. Both cell types were susceptible to the cytotoxic effect of ATPo, but killing of the L929/R variant required much shorter incubations in the presence of this nucleotide. Morphologic examination of ATPo-challenged L929 and L929/R cells showed that cell death occurred by two alternative mechanisms: colloido-osmotic lysis or apoptosis. Occurrence of apoptosis was confirmed by agarose gel analysis of cellular DNA. Although ATPo caused a fast mobilization of intracellular Ca2+, neither colloido-osmotic lysis nor apoptosis were Ca2+ dependent. Our results show that the L929/R variant, but not the L929 parental fibroblast cell line, expresses functional purinergic receptors of the P2z subtype. The presence of P2z receptors confers to L929/R cells enhanced susceptibility to ATPo-mediated cytotoxicity. PMID- 1431112 TI - Release of granulocyte-macrophage colony-stimulating factor by alveolar macrophages in the lung of HIV-1-infected patients. A mechanism accounting for macrophage and neutrophil accumulation. AB - In this paper, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lung of patients with HIV-1 infection was evaluated. This cytokine has well recognized effects on granulocyte and macrophage growth and differentiation and plays some role in the mechanisms leading to the accumulation of alveolar macrophages (AM) in patients with interstitial lung disease. Detectable levels of GM-CSF (up to 10 pg/ml) were demonstrated in unconcentrated bronchoalveolar lavage fluid retrieved from HIV-1-seropositive patients, thus suggesting that the GM-CSF is released in vivo in the lung during HIV-1 infection. A statistically significant correlation was demonstrated between the bronchoalveolar lavage concentrations of GM-CSF and the absolute numbers of AM and lung neutrophils. Cell-free supernatants obtained from unstimulated 24-h cultured AM isolated from HIV-1-infected patients contained discrete amounts of GM-CSF, as demonstrated by an immunoenzymatic assay. AM lost the capability of releasing GM-CSF after 72 h of culture, thus suggesting that the production of GM CSF is not constitutive in AM. After exposition of AM with LPS, the release of GM CSF and the expression of its mRNA significantly increased with respect to the baseline values; interestingly, the amount of GM-CSF released by LPS-stimulated AM was more than 10-fold higher in HIV-1-infected patients than in healthy subjects. As demonstrated by flow cytometry analysis, more than 70% of freshly isolated AM efficiently bound phycoerythrin-GM-CSF, thus indicating that they express the receptor for GM-CSF. Determination of AM in G1, S, and G2+M by flow cytometry showed that, after 48 h of culture with GM-CSF, 5.5 to 7% of AM entered the proliferative phase of the cell cycle. Taken together, these findings suggest that AM might represent an important source of GM-CSF production in HIV-1 infection. In particular, the hypothesis is formulated that pulmonary opportunists might trigger AM to synthesize GM-CSF in situ. The local overproduction of this cytokine is likely to play a role in the pathogenic events leading to the local proliferation of AM and recruitment of neutrophils in AIDS associated interstitial lung disease. PMID- 1431113 TI - Redox status of cells influences constitutive or induced NF-kappa B translocation and HIV long terminal repeat activity in human T and monocytic cell lines. AB - We have tested the hypothesis that cellular activation events occurring in T lymphocytes and monocytes and mediated through translocation of the transcription factor NF-kappa B are dependent upon the constitutive redox status of these cells. We used phenolic, lipid-soluble, chain-breaking antioxidants (butylated hydroxyanisole (BHA), nordihydroquairetic acid, or alpha-tocopherol (vitamin E) to show that peroxyl radical scavenging in unstimulated and PMA- or TNF stimulated cells blocks the functions depending on NF-kappa B activation. BHA was found to suppress not only PMA- or TNF-induced, but also constitutive, HIV enhancer activity concomitant to an inhibition of NF-kappa B binding activity in both lymphoblastoid T (J.Jhan) and monocytic (U937) cell lines. This was also true for KBF (p50 homodimer) binding activity in U937 cells. Secretion of TNF, the product of another NF-kappa B-dependent gene, was abolished by BHA in PMA stimulated U937 cells. The anti-oxidative effect of BHA was accompanied by an increase in thiol, but not glutathione, content in stimulated and unstimulated T cell, whereas TNF stimulation itself barely modified the cellular thiol level. Oxidative stress obtained by the addition of H2O2 to the culture medium of J.Jhan or U937 cells could not by itself induce NF-kappa B activation. These observations suggest that TNF and PMA do not lead to NF-kappa B activation through induction of changes in the cell redox status. Rather, TNF and PMA can exert their effect only if cells are in an appropriate redox status, because prior modification toward reduction with BHA treatment prevents this activation. It appears that a basal redox equilibrium tending toward oxidation is a prerequisite for full activation of transduction pathways regulating the activity of NF-kappa B-dependent genes. PMID- 1431114 TI - A combined immunodeficiency with oligoclonal CD8+, V beta 3-expressing, cytotoxic T lymphocytes in the peripheral blood. AB - The diagnosis severe combined immunodeficiency was made in a male infant at the age of 18 wk. Known causes of severe combined immunodeficiency were excluded. The activity of total 5'-nucleotidase (E.C. 3.1.3.5) in the PBMC was found to be strongly decreased. Analysis of the peripheral blood revealed a lymphocytosis, mainly of CD8+ T cells. These lymphocytes expressed high levels of CD29, CD38, CD45RA, and MHC class II molecules but no CD25, CD26, CD27, or CD28 Ag. The cells proliferated poorly to all T cell stimulants tested and no helper activity for IgM secretion could be induced. In contrast to the poor proliferative responses, high levels of TCR-induced cytolytic activity, without lymphokine-activated killer-cell outgrowth, were induced by CD3 mAb. Analysis of TCR-beta gene rearrangements indicated that two clonal populations constituted the majority of the E-rosette+ peripheral blood fraction. Moreover, the vast majority of the CD8+ cells were found to react with a mAb to V beta 3. Polymerase chain reaction on cDNA from peripheral blood cells with primers that amplify TCR V beta elements showed, in agreement with the fluorescence data, an overrepresentation of V beta 3 but absence of usage of approximately 50% of the other V beta elements. Thus, in a severe combined immunodeficiency patient, CD8+ T cells with limited T cell receptor usage and restricted effector functions were found. The observed alterations in the 5'-nucleotidase levels may be secondary to the outgrowth of this population. PMID- 1431115 TI - Distinctive HLA-A,B antigens of black populations formed by interallelic conversion. AB - Alleles encoding five HLA-A and B Ag characteristic of black populations have been isolated and their nucleotide sequences determined. In each case, the "black" allele is similar to a "related" allele found in caucasoid populations. The primary differences between these pairs of alleles are localized clusters of nucleotide substitutions that change two to five residues of the Ag recognition site. The pattern of differences indicates that the pairs of black and caucasoid alleles diverged primarily as a result of interallelic conversion events. PMID- 1431116 TI - Idiotypic and antiidiotypic T and B lymphocytes in myasthenia gravis. AB - The prevalence of Id and anti-Id T and B cells as measured by their reactivities with two human mAb, one antiacetylcholine receptor mAb and one anti-Id mAb, was studied in 38 patients with myasthenia gravis and in 27 healthy individuals. Id and anti-Id T cells were estimated by enumerating the numbers of cells secreting IFN-gamma in response to 10 pg/ml of the human mAb. T cell stimulation, measured as numbers of IFN-gamma-secreting cells that exceeded the mean + 2 SD of controls, was induced by the Id mAb in 78.9% of the patients and in 7.4% of the controls, whereas the anti-Id mAb-stimulated T cells in 55.3% of the patients and in 3.7% of the controls. The mean value of the Id and anti-Id-reactive T cells in the patients was 18.3/10(5) and 10.1/10(5) PBMC, respectively. B cells secreting IgM antibodies binding to the human mAb were increased in patients with myasthenia gravis compared to healthy controls. Seventy-five percent of the patients and 12% of the controls had B cells secreting IgM antibodies binding to the Id mAb, although 89% of the patients and 16% of the controls had B cells secreting IgM antibodies binding to the anti-Id mAb. The mean value of B cells secreting IgM antibodies binding to Id or anti-Id mAb in the patients were 7.4 cells/10(6) and 5.5 cells/10(6) PBMC, respectively. We conclude that Id and anti Id T and B cells are present in myasthenia gravis. These methods allow a quantitative estimation of T and B cells with defined specificities and thus a way of mapping the repertoire of lymphocytes. PMID- 1431117 TI - Freshly isolated, murine neonatal T cells produce IL-4 in response to anti-CD3 stimulation. AB - In previous studies of chimeric animals, we found that fetal intrathymic T cell precursors give rise to phenotypically abnormal peripheral T cell populations. Because most peripheral T lymphocytes in newborn mice are the progeny of fetal T cell precursors, this result led to the hypothesis that neonatal and adult T cells differ in their functional capacities. To investigate this issue, the responses of neonatal and adult T cells to anti-CD3 antibody and TCR-independent stimulation were compared. When stimulated with soluble anti-CD3 antibody in the presence of adult accessory cells, neonatal T cell proliferation was markedly decreased compared with that of adult T cells. This reduction in proliferation was associated with both quantitative and qualitative differences in lymphokine production. At 48 h of stimulation with anti-CD3 antibody, neonatal T cells produced at least 10-fold less IL-2 than adult T cells. This apparently accounted for their reduced proliferation because the addition of exogenous IL-2 restored their proliferation to the levels achieved by adult T cells. In striking contrast to adult T cells, neonatal T cells secreted large amounts of IL-4 upon primary stimulation in vitro. The differences between neonatal and adult T cells in proliferation and lymphokine production were shown to be specific for CD3 mediated stimulation. In the presence of phorbol ester and calcium ionophore, neonatal and adult T cells showed equivalent proliferation and IL-2 production. Under these conditions, IL-4 production by neonatal or adult T cells was essentially undetectable. Thus, in response to TCR-independent stimulation, freshly isolated neonatal and adult T cells show similar functional responses. However, when stimulation occurs via the CD3 components of the TCR, the responses of neonatal T cells resemble those of primed T cells from adult animals. PMID- 1431118 TI - Enhanced antigen presentation using human Fc gamma receptor (monocyte/macrophage) specific immunogens. AB - A major new challenge for vaccine development is to target APC such as monocytes and macrophages for efficient Ag processing and presentation. It has been shown that Fc gamma R-mediated uptake of Ag-antibody complexes can enhance Ag presentation by myeloid cells at least 100-fold, and directing Ag to Fc gamma R in mice brings about a substantial increase in the effectiveness of immunization while eliminating the requirement for adjuvant. It has not been determined which of the three subclasses of human Fc gamma R on myeloid cells (Fc gamma RI, Fc gamma RII, or Fc gamma RIII) function to enhance Ag presentation. We have targeted our Ag (TT) to each of the three subclasses of human Fc gamma R on monocytes using Fc gamma R subclass-specific mAb-TT conjugates, and have measured TT presentation by monitoring T cell proliferation in response to TT. In addition, we have examined enhanced Ag presentation mediated by a human IgG1 (HIgG1) anti-TT mAb. All anti-Fc gamma R-TT conjugates enhanced Ag presentation. HIgG1 anti-TT, in monomeric form, enhanced Ag presentation through Fc gamma RI only. Anti-Fc gamma RI-Ag conjugates appear to be optimal for application as vaccines. They are monocyte/macrophage-specific, are very efficiently processed and presented, and enhance Ag presentation despite occupation of Fc gamma RI with HIgG. PMID- 1431119 TI - Evidence for a role for T cell receptors (TCR) in the effector phase of acute bone marrow graft rejection. TCR V beta 5 transgenic mice lack effector cells able to cause graft rejection. AB - Lethally irradiated mice reject within 24 h certain marrow grafts, a phenomenon called either allogeneic or hybrid resistance. The cells responsible for this rejection (NK1+ CD3+ cells (TNK) express Ag of NK cells as well as the TCR associated CD3 complex. This raises the question whether TCR participate in the function of these cells during graft rejection. By using flow cytometry it is shown that the majority of TNK cells expresses the TCR-alpha/beta chains and by using adoptive cell transfer assays evidence is presented that it is the TCR alpha/beta expressing cells that cause rejection. To explore whether any particular TCR chains have to be expressed on these cells, C57L mice were assayed and found to be responders suggesting that the V beta chains deleted in these mice are not obligatory. However, introduction of a specific TCR V beta 5 chain into C57BL/6 mice as a transgene leads to inability to transfer resistance. TNK cells of V beta 5 transgenic mice express the introduced gene suggesting that it is the transgenic TCR that is responsible for the lack of function. In assessing T cell functions in V beta 5 transgenic mice it is shown that although these mice generate CTL specific for H-2d targets there is a deficiency to recognize H-2Dd, i.e., of determinants presumed to be recognized in the acute rejection mechanism. Thus TNK cells and CTL share the inability to recognize H-2Dd epitopes due to expression of the V beta 5 transgene. The notion that TCR on TNK cells play a role in the acute rejection process makes it necessary to postulate a receptor selection mechanism for these cells. PMID- 1431120 TI - Gamma delta T cells assist alpha beta T cells in adoptive transfer of contact sensitivity. AB - Cutaneous immune responses to contact sensitizers such as picryl chloride or oxazolone, are classical manifestations of T cell-mediated immunity in vivo. In fact, the first documentation of T cell-mediated immunity was the ability to adoptively transfer contact sensitivity (CS) responses. Although it is now clear that Ag/MHC-restricted alpha beta TCR positive effector T cells are responsible for 24 to 48 h CS responses, other subsets of Thy-1+ cells in mice also participate in the elicitation of CS. Thus, Thy-1+, CD5+, CD3-, B220+, hapten specific, non-MHC-restricted early-acting cells are required to initiate CS responses by leading to local serotonin release, which allows for extravascular recruitment of the late-acting, alpha beta TCR+, CS effector T cells. This study describes another T cell population that is needed for the adoptive transfer of CS by alpha beta T cells. In vitro treatment of a mixture of CS effector cells with hamster mAb to gamma delta TCR, together with rabbit complement, or by panning on anti-hamster Ig-coated dishes, diminished substantially the subsequent transfer of CS reactivity without affecting either CS-initiating cells, or the later-acting, alpha beta TCR+ CS effector T cells. Immune cells treated with anti alpha beta TCR mAb, or recovered as adherent cells from petri dishes after anti gamma delta TCR panning (i.e., gamma delta TCR-enriched cells), reconstituted the ability of anti-gamma delta TCR-treated immune cells (i.e., alpha beta TCR enriched cells) to transfer 24-h CS responsiveness. The phenotype of the gamma delta T cells that assisted CS effector alpha beta T cells was: CD3+, CD4-, and CD8+. The gamma delta T cells that assisted alpha beta T cells were not Ag specific since anti-alpha beta-TCR-treated cells (gamma delta T-enriched) from picryl chloride immunized donors aided alpha beta T cells (anti-gamma delta TCR treated) from oxazolone-immunized donors, and conversely gamma delta T cells from oxazolone-immunized donors aided alpha beta T cells from picryl chloride immunized donors. Furthermore, the CS-regulating gamma delta T cells were not MHC restricted because gamma delta T cells from H2d or H2b donors could assist alpha beta T cells from H2k donors. It was concluded that a regulatory population of non-Ag specific, non-MHC-restricted gamma delta T cells was needed to assist immune effector, Ag/MHC-specific alpha beta T cells in the adoptive transfer of CS. PMID- 1431121 TI - Poly-(ADP-ribose) polymerase partially contributes to target cell death triggered by cytolytic T lymphocytes. AB - We hypothesized that CTL-induced target cell (TC) death is partially due to processes that follow the DNA damage in target cells and include the activation of poly-ADP-ribose transferase (PADPRT) by DNA strand breaks. According to this model, the activated PADPRT is expected to deplete NAD, ATP, and to contribute to the TC death. We used inhibitors of PADPRT and a PADPRT-deficient cell mutant, as well as other nucleated TC and SRBC to test the role of PADPRT in CTL-induced cytotoxicity. It is found that inhibitors of PADPRT (3-aminobenzamide, benzamide (aromatic amides)) and nicotinamide all inhibit the CTL-mediated lysis of both Ag specific TC and of Ag-nonbearing TC. The effect of PADPRT inhibitors was not due to inhibition of the lethal hit delivery by CTL, because in parallel control experiments, the same inhibitors did not interfere with CTL-induced lysis of SRBC, cells that are devoid of nuclei and PADPRT. Moreover, the effect of inhibitors of PADPRT did not affect earlier stages of lethal hit delivery because 3-aminobenzamide and benzamide did not interfere with CTL-induced DNA fragmentation in TC at concentration which protected TC lysis. Importantly, a PADPRT-deficient cell line was also much more resistant to CTL-induced lysis as tested in retargeting (4 and 8 h) assays; this was expected if activation of PADPRT is indeed involved in TC death. Control experiments reveal that the relative resistance of the PADPRT-deficient cell mutant to CTL-induced lysis was not related to its impaired ability to form conjugates and to trigger CTL (as tested in granule exocytosis assay). In addition, PADPRT-deficient cells were as susceptible to CTL-induced DNA fragmentation as were the control cells; yet, they were resistant to CTL-induced 51Cr-release. Control cells and PADPRT-deficient mutant were equally susceptible to antibody+C'-mediated lysis. Our data support the view that the activation of PADPRT can contribute to the CTL-induced cytolysis of some TC, but is not involved in lysis of other TC, as evidenced by the ability of CTL to efficiently lyse SRBC. These data suggest that there could be multiple molecular pathways of TC death in CTL-mediated cytotoxicity and the relative contribution of PADPRT and/or other enzymes will reflect the individual make-up of a particular TC. PMID- 1431122 TI - Expression of VLA-4 on thymocytes. Maturation stage-associated transition and its correlation with their capacity to adhere to thymic stromal cells. AB - The present study investigates the expression of VLA-4 on thymocytes at various stages of maturation and their capacity to adhere to thymic stromal cells. Whole thymocytes were stained with anti-CD4 and anti-CD8, as well as anti-VLA-4 antibodies. Flow microfluorometric analyses revealed that a) most of CD4-8- (double negative DN) and CD4-8intermediate thymocyte populations expressed large amounts of VLA-4, b) the levels of VLA-4 were considerably and markedly reduced on CD4+8+ (double positive DP) and single positive (SP) (CD4+8- or CD4-8+) populations, respectively. This contrasted with an increase in the levels of LFA 1 along with thymocyte maturation. DN, DP, and SP subsets were isolated and examined for their capacity to express VLA-4 and to adhere to fibronectin (FN) molecules as well as thymic stromal cells expressing FN. DN, DP, and SP subsets were confirmed to express the respective high, low, and very low levels of VLA-4, respectively. Approximately 70% of DN thymocytes became bound to FN-precoated culture plates, whereas 30 to 40% of DP and only 10 to 20% of SP cells adhered to FN. Similar patterns of adhesion were observed between these thymocyte subsets and thymic stromal monolayers. The binding of the DN subset to FN-plates or thymic stromal monolayers was inhibited only marginally by the RGDS peptide, but was efficiently inhibited by V10 peptide (cell-binding sequence that is located in the V region on FN and reacts with the VLA-4 integrin) or anti-VLA-4 antibody. Anti-VLA-4 antibody plus RGDS peptide strongly inhibited DN cell binding to FN coated plates and thymic stromal monolayers. These results indicate that i) VLA-4 expressed on DN thymocytes functions as an important integrin for interacting with thymic stromal cells; ii) the expression level of this integrin decreases with the progress of thymocyte maturation, and iii) most of the mature thymocytes (SP) are rendered less adhesive to thymic stromal cells by reducing the level of VLA-4 expression. PMID- 1431123 TI - Cytokine pattern of Langerhans cells isolated from murine epidermal cell cultures. AB - In the present study we demonstrate that supernatants of highly enriched cultured Langerhans cells (cLC) display IL-1, IL-6, granulocyte/macrophage (GM)-CSF, and TNF-alpha, but no IL-2, IL-3, IL-4, and IFN-gamma activities. We further show that IL-6, GM-CSF, and TNF-alpha bioactivities can be specifically blocked in the presence of the respective neutralizing mAb. Concerning the IL-1 bioactivity, the combined use of anti-IL-1 alpha and anti-IL-1 beta mAb was needed to completely inhibit the proliferative response of the indicator cell line D10. One of the difficulties in studying the secretory potential of LC is that even highly enriched cLC are contaminated with keratinocytes (KC), which are known to be a rich source of cytokines. To overcome this problem we compared cytokine bioactivities in supernatants of cell cultures consisting of selected cLC:cKC ratios. These cell mixing experiments revealed that cLC are the major source of the IL-6 bioactivity, whereas IL-1, GM-CSF, and TNF-alpha are predominantly generated by cKC. In order to determine whether the cytokine bioactivities measured in supernatants of epidermal cell cultures are simply caused by an increased release or by de novo synthesis, we performed molecular biologic studies. Polymerase chain reaction analysis of cLC and cKC revealed that IL-1 beta and IL-6 transcripts are virtually limited to cLC, whereas IL-1 alpha, GM CSF, and TNF-alpha messages are preferentially exhibited by cKC. mRNA coding for IL-2, IL-3, IL-4, and IFN-gamma could neither be amplified from cLC nor from cKC. Furthermore, the quantitative comparison of cytokine transcripts in cLC vs cKC using Northern blot analysis and mRNA detection on the single cell level using in situ hybridization confirmed that cLC generate IL-6, whereas cKC synthesize IL-1 alpha and GM-CSF. Taken together our results demonstrate that cultured murine LC synthesize and secrete IL-1 beta and IL-6, cytokines known to be important accessory molecules in T cell activation. PMID- 1431124 TI - The presence in a mouse T cell line of a 97-kDa protein kinase C (PKC) with characteristics similar to known members of the novel PKC subgroup and its possible role in lymphocyte gene expression. AB - The receptor for tumor-promoting phorbol esters has been shown to be the Ca+2/phospholipid dependent enzyme protein kinase C (PKC). There are two major groups of PKC, the conventional PKC isotypes alpha, beta I, beta II, gamma) and the novel Ca+2-independent PKC (delta, epsilon, zeta, eta). Phorbol esters previously have been demonstrated to increase human IFN-gamma gene expression after treatment of a murine T cell line (Cl 9) that has been transfected with human IFN-gamma genomic DNA. In contrast, treatment with Ca+2 ionophore alone or in combination with phorbol ester did not enhance IFN-gamma production in a synergistic manner above the level obtained with phorbol ester treatment alone. To determine whether the lack of effect of Ca+2 ionophore is due to a defect in PKC, we compared the level of PKC autophosphorylation in the mouse T cell line (Cl 9), a mouse epidermal cell line (JB6), and purified rat brain PKC by in vitro kinase assays. The results demonstrate that instead of the expected 80-kDa autophosphorylated PKC band seen in purified rat brain PKC or mouse JB6 cell lysates, only a novel 97-kDa Ca+2-independent phosphoprotein was observed in Cl 9 cells. To ascertain if there was any nucleic acid sequence similarity to PKC epsilon, we hybridized Cl 9 poly(A+) RNA with a cloned fragment of the PKC epsilon gene and observed two hybridizing RNA bands (4.4 and 4.0 kb). Our results suggest that the 97-kDa phosphoprotein is similar to, but not identical with, PKC epsilon and is the major PKC expressed in the Cl 9 murine T cell line. These data suggested that the 97-kDa PKC may be responsible for the induction of both the transfected human IFN-gamma gene and the endogenous murine IL-2R alpha-chain. PMID- 1431125 TI - Primary structure of cobra complement component C3. AB - Complement component C3 is a multifunctional protein known to interact specifically with more than 10 different plasma proteins or cell surface receptors. Cobra venom contains cobra venom factor, a structural analogue of C3 that shares some properties with C3 (e.g., formation of a C3/C5 convertase) but differs in others (e.g., susceptibility to regulation by factors H and I). The elucidation of structural differences between C3 and cobra venom factor can be expected to help identify functionally important regions of C3 molecules. To that end we have undertaken the molecular cloning of both cobra C3 and cobra venom factor to take advantage of the unique biologic system where both proteins are produced by the same species. We report the primary structure of cobra C3 mRNA and the derived protein structure. Cobra C3 mRNA is 5211 bp in length. It contains an open reading frame of 4953 bp coding for a single pre-pro-C3 molecule, consisting of a 22-amino acid signal sequence, a 633-amino acid beta chain (70 kDa), and a 992-amino acid alpha-chain (112 kDa) which is separated from the beta-chain by four arginine residues. There are no N-glycosylation sites in cobra C3. Cobra C3 exhibits approximately 58% nucleotide sequence identity with C3 from mammalian species. At the protein level, sequence identity is approximately 52% and sequence similarity approximately 71%. All 27 cysteine residues are highly conserved as are the C3 convertase cleavage site, the thioester site, and the factor B binding site. Cobra C3 also seems to have homologous binding sites for factor H and properdin, as well as a conserved sequence in the functionally important region of the C3a anaphylatoxin. The sequence homology at the CR2 and CR3 binding sites does not exceed the overall sequence homology. Accordingly, the existence of CR2 and CR3 binding sites can neither be deduced nor excluded. PMID- 1431126 TI - Cross-reactivity of IgM-secreting B cells from normal BALB/c mice. AB - Cross-reactive antibodies capable of binding to foreign and self Ag are present in the serum of normal newborn and adult animals. In our work, a chamber ELISA assay was used to quantitate the cross-reactivity of B cells actively secreting Ig in BALB/c mice of different ages. Individual lymphocytes were tested for the production of IgM antibodies capable of binding to a series of four unrelated Ag (DNA, TNP, actin, and OVA). Results indicate that nearly one-quarter of IgM secreting lymphocytes from 6-day-old animals were cross-reactive. This frequency was two- to fourfold higher than that found in adult mice. Very old animals, however, showed a selective increase in the cross-reactivity of anti-DNA (but not anti-TNP) secreting lymphocytes. Evidence from Ag inhibition experiments indicated that low concentrations of soluble Ag could block the binding of polyreactive antibodies, and that approximately one-half of "naturally" cross reactive B cells produced antibodies capable of binding to three or more unrelated Ag. PMID- 1431127 TI - Restricted IgH V gene usage in the response to the ese epitope on "Hi" sheep red blood cells. AB - We had previously shown that the in vitro antibody response to a single epitope (ese; extra sheep E Ag) present on some sheep E but absent from others could be monitored by assay of the plaque-forming cell response on both Lo3 and Hi SRBC. We had shown also that the response was seen only in certain strains of mice and that the gene(s) controlling the response mapped to the IgH V region of the IgH chain complex. An additional feature of the response is that it is only seen in vitro and is absent and, we hypothesize, is suppressed in vivo. The strain distribution of the response to the ese determinant suggested that the response may only use one V gene (or a small set of closely related V genes) that would be present in the responder strains and absent from the nonresponder strains. To test this hypothesis, we made hybridomas with specificity for the ese determinant and for the shared determinants. cDNA from these hybridomas were sequenced. All four anti-ese hybridomas were almost identical in V region sequence, but varied considerably in D and J segment usage, thus confirming the hypothesis that the ese response would be limited at the V segment. The four anti-ese hybridomas used two Vh J558 genes that differed only by one, or possibly two, nucleotide(s). Importantly, these genes are quite different from most other published J558 sequences. The sequence is very similar to an unexpressed sequence from a C57Bl/6 perinatal mouse and slightly less similar to two other Vhb sequences. It was quite similar to two sequences from autoantibodies, one an anti-DNA hybridoma antibody, BXW-14, isolated from an NZB x NZWF1 mouse, and the other, an NZB hybridoma, G8, with specificity for a mouse E Ag. We speculate that the Ig encoded by the V ese gene react with an autoantigen, that the B cells persist in the animal, but that the secretion of Ig is somehow suppressed. PMID- 1431128 TI - The anti-DNA-associated idiotype 8.12 is encoded by the V lambda II gene family and maps to the vicinity of L chain CDR1. AB - The 8.12 idiotype is an anti-DNA-associated Id present on lambda L chains that are expressed at high titers in 50% of patients with systemic lupus erythematosus. Since this Id can be present on as much as a third of a patient's anti-DNA antibodies and is found in renal glomeruli, 8.12 is thought to be a marker for a subset of pathogenic anti-DNA auto-antibodies. A molecular analysis of the 8.12 positive antibodies was designed to explore the genetic basis of this Id. Monoclonal human B cell lines were generated by transformation with EBV and lambda L chain-secreting lines were analyzed for Id expression and V region gene usage. In this panel of Ig lambda cell lines, the 8.12 idiotype is encoded exclusively by members of the V lambda II gene family. The sequences of several 8.12+ and 8.12- V lambda II genes are reported here and are used to map the 8.12 Id to the vicinity of CDR1, as well as to further characterize the large and polymorphic V lambda II gene family. PMID- 1431129 TI - CD4 changes conformation upon ligand binding. AB - Aurintricarboxylic acid (ATA) has been shown to block the binding site for both HIV gp120 and mAb anti-Leu 3a on CD4. We have unexpectedly found that brief treatment with > or = 1 micrograms/ml ATA rapidly disengages another mAb, OKT4E, after it has been bound to CD4 on human PBL. OKT4E is specific for a discontinuous epitope overlapping the MHC class II-binding region in the N terminal CD4 domain. Interestingly, among 10 other mAb tested, only anti-Leu 8, specific for a leukocyte homing receptor is also quickly released from the cells by ATA treatment. Disengagement of the OKT4E mAb is also seen on a CD4-positive cell line (HPB-ALL) and with recombinant soluble CD4 (sCD4) bound to immobilized OKT4E. In all of these cases, disengagement is prevented if OKT4E is cross linked, or the Leu 3a site is blocked by the mAb, but not by gp120. Photobleaching fluorescence resonance energy transfer (pFRET) measurements suggest that OKT4E is released as an indirect consequence of ATA-evoked conformational changes of CD4. Similar changes were detected as a result of gp120 binding to PBL. These data raise the possibility of a novel type of immunomodulation: induced disengagement of a bound ligand from its Ag. PMID- 1431130 TI - Biochemical specificity of H-2M3a. Stereospecificity and space-filling requirements at position 1 maintain N-formyl peptide binding. AB - The maternally transmitted Ag is a cell surface product of three gene products: 1) H-2M3a (formerly Hmta), a class I MHC heavy chain; 2) beta 2-microglobulin; and 3) maternally transmitted factor (Mtf), the N-terminus of the mitochondrially encoded ND1 subunit of the reduced form of nicotinamide-adenine dinucleotide dehydrogenase. This class I molecule has been shown to be an N-formyl peptide receptor. Although the N-formyl moiety is necessary for binding to M3a, it is not sufficient. We proposed that the R group of the amino acid in position 1 plays a pivotal role in peptide binding to M3a. To test this hypothesis, analogues differing in size and stereospecificity of the R group were synthesized. Substitutions with other hydrophobic amino acids such as N-formyl phenylalanine and N-formyl valine had no significant effect on the ability of these Mtf alpha analogues to sensitize target cells (M3a, Mtf beta) to M3a, Mtf alpha-specific CTL. In contrast, the nonsubstituted, N-formylated, and N-acetylated glycyl analogues of Mtf beta bound equivalently to M3a in a peptide competition assay. Moreover, the alanine analogue bound in an N-formyl-dependent manner. To determine the limitations of the putative N-formyl pocket, peptide analogues were constructed incorporating D-isomer amino acids. When formylated D-alanine or D methionine replaced the native methionine, these peptide derivatives did not show significant binding to M3a. Therefore, the presence of a space-filling R group (greater than hydrogen) is necessary for an antigenic peptide to bind M3a in an N formyl-dependent manner. Additionally, the ability of M3a to discriminate between the optical forms of methionine and alanine demonstrates that this N-formyl pocket is stereospecific in its ability to bind peptide. Thus, we have defined three requirements for peptide binding to M3a: an N-formyl moiety at the amino terminus of the peptide, a space-filling R group at position 1 to maintain this N formyl specificity, and the correct stereoisomer of the first amino acid. PMID- 1431131 TI - Induction of protective immunity in mice using a 62-kDa recombinant fragment of a Schistosoma mansoni surface antigen. AB - Mice exposed to radiation-attenuated cercariae of Schistosoma mansoni are highly resistant to challenge infection, and sera from these mice can confer partial resistance when transferred to naive recipients. These sera recognize Ag present in schistosomular and adult worms, among them an Ag of 200 kDa. A cDNA encoding a 62-kDa portion of this Ag was cloned; the deduced amino acid sequence of this cDNA clone shares homology with myosins of other species. To assess the immunoprophylactic potential, we carried out vaccination trials in mice using the recombinant polypeptide expressed as a fusion protein with beta-galactosidase presented in the form of proteosome complexes with the outer membrane protein of meningococcus. The level of protection achieved was 32%, and this level could be increased to 75% by removal of those amino acids included in the fusion protein that were derived from the vector to yield a polypeptide, designated rIrV-5. A similar level of protection was achieved when mice were immunized with the same dose of rIrV-5 in the form of protein complexes but without outer membrane protein, suggesting that protection did not require the use of adjuvant. However, at least three immunizations were necessary to achieve protection. Using mAb and sera from mice vaccinated with rIrV-5, we demonstrated that the native protein recognized by antibodies against rIrV-5 is a 200-kDa protein that is expressed on the surface of newly transformed schistosomula. The protection achieved with rIrV 5 in mice encourages additional studies of its potential as a vaccine candidate for the prevention of schistosomiasis. PMID- 1431132 TI - Protection of mice and nude rats against toxoplasmosis by a multiple antigenic peptide construction derived from Toxoplasma gondii P30 antigen. AB - The first part of this work presents the sequence of the first 20 NH2 terminus residues obtained from P30, the major surface Ag of Toxoplasma gondii, purified by HPLC. A synthetic peptide (P30 48-67) has been prepared both in linear form and as a multiple antigenic peptide (MAP) construct. Immunization of mice and rats with the P30 48-67 MAP in the presence of IFA induces high levels of IgG antibodies that recognize both the linear peptide and the MAP construct in ELISA, and P30 in Western blots of NP-40-extracted tachyzoite Ag. Because these sera are negative in immunofluorescence assays with whole tachyzoites, it seems that IgG antibodies induced by P30 48-67 MAP, although recognizing the denatured structure, are unable to recognize the native protein. However, the protective effect of both constructs has then been studied in mice and nude rats. Whereas immunization of mice with the monomeric peptide does not confer any protection against oral infection with 1200 cysts of T. gondii 76K strain (mortality within 11 days), 40% of mice immunized with the MAP construct survived up to 75 days after infection. Nude rats were passively transferred with 5 x 10(4) T lymphocytes from P30 48-67 MAP-immunized Fischer rats before infection with 5 x 10(4) RH strain tachyzoites. They survived up to 40 days after infection and raised an intense IgG antibody response against P30, whereas nude rats transferred with control lymphocytes died within 21 days. This shows that immunization with P30 48-67 MAP also induces an efficient T cell immune response. The present work confirms the recently demonstrated role of P30 in protective immunity and shows the interest of peptide octameric constructions as inducers of partially protective immune responses in toxoplasmosis, as already demonstrated in schistosomiasis. PMID- 1431133 TI - Depletion of eosinophils by anti-IL-5 monoclonal antibody treatment of mice infected with Trichinella spiralis does not alter parasite burden or immunologic resistance to reinfection. AB - Mechanisms of parasite killing by eosinophils are widely studied and are often implicated in mediating resistance to parasitic infection, especially in conjunction with specific antibodies. Evidence for the eosinophil as an anti parasite killer cell in vivo is limited and may not justify the belief that eosinophils engage and/or kill infective helminths. We reexamined this question in a mouse model of trichinosis in which antisera to eosinophils were previously used to show the requirement for eosinophils in resistance to this nematode. The current studies used mAb to IL-5 to suppress eosinophil levels in CF1 mice infected with Trichinella spiralis. In mice given a primary infection and injected with an isotype control mAb or left untreated, the medullary and peripheral blood eosinophil numbers peaked at 3 wk postinfection (PI) and returned to baseline levels by 4 wk PI. Peripheral blood eosinophil numbers in infected mice injected with anti-IL-5 were maintained at levels below those of uninfected normal mice through 4 wk of infection. Histologically, there was a prominent eosinophil accumulation in infected, untreated, or control-mAb-treated mice associated with nurse cell complexes containing infective juveniles in skeletal muscle at 3 and 4 wk PI. This was largely eliminated in mice treated with anti-IL-5 mAb. However, the number of muscle stage juvenile worms recovered 3 and 4 wk PI after acid pepsin digestion was unaffected by eosinophil depletion. Challenge infections, in which mice were infected at day 0 with 125 muscle stage worms and challenged at day 28 PI with 350 muscle stage worms, developed peak eosinophil numbers in bone marrow and peripheral blood 3 wk after primary infection and 2 wk after challenge infection in mice receiving either no treatment or control mAb. In challenged mice receiving anti-IL-5 mAb, medullary and peripheral blood eosinophil numbers remained at or below those of uninfected animals. Although all groups exhibited significant resistance measured as muscle stage worm burdens 56 days PI, eosinophil depletion did not affect resistance of muscle worm recovery. These results suggest that eosinophils are not essential in the control of T. spiralis in either primary or challenge infections of CF1 mice. This in vivo study illustrates the questionable value of in vitro killing assays to assign effector function to any single inflammatory cell type. PMID- 1431134 TI - The hamster immune response to tick-transmitted Borrelia burgdorferi differs from the response to needle-inoculated, cultured organisms. AB - The human immune response to natural infection with Borrelia burgdorferi appears to differ from that seen in small mammals infected by needle inoculation. In humans, antibody to outer surface proteins A and B (OspA and OspB) is not detectable until late in infection, but small mammals inoculated with B. burgdorferi produce early antibody to OspA and OspB. To investigate this disparity we compared the immune response in hamsters to B. burgdorferi after needle inoculation with cultured organisms or infected tick homogenates with the immune response after tick transmitted (natural) infection. We determined that the antibody response to OspA and OspB after natural infection of hamsters is similar to that seen in humans, and differs from the antibody response after hamster infection by needle inoculation. High titers of antibody to OspA and OspB were undetectable even 42 wk after bite by B. burgdorferi-infected ticks. The failure to produce antibody to OspA and OspB was not dependent on challenge dose, because animals inoculated by needle with low doses (1 x 10(5) to 1 x 10(6) cells) of B. burgdorferi produced antibody to OspA and OspB. A rapid but limited anti-41-kDa response was observed. One possible new Ag, 43 kDa (p43), was identified. The antibody response to p43 was independent of the route of inoculation. Our results suggest that the hamster immune response to tick transmitted Borrelia burgdorferi differs from the response to needle inoculated, cultured organisms. PMID- 1431135 TI - Monoclonal antibody to IFN-gamma modifies pulmonary inflammatory responses and abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae. AB - In C57Bl/6 mice vaccinated with a single dose of attenuated cercariae of Schistosoma mansoni, the major site of immune elimination of intact challenge parasites is the lungs. The effector mechanism involves the formation of focal inflammatory responses throughout the pulmonary tissues. These foci are rich in CD4+ T cells, believed to be memory:effector cells of the Th1 type. To investigate the role of IFN-gamma in these inflammatory responses, vaccinated mice were treated with neutralizing mAb. Administration on days 4, 8, 12, and 16 post-challenge, the period over which elimination of challenge parasites takes place in the lungs, gave an average 89.5% abrogation of protective immunity. Analysis of pulmonary cell populations recovered by bronchoalveolar lavage from treated nonimmune mice at day 14 post-challenge revealed a sharp increase in pulmonary eosinophilia, relative to intact vaccinated and challenged animals. The inverse relationship between eosinophilia and protection suggests that eosinophils do not play a vital role in the immune effector mechanism in this model. Pulmonary foci of treated mice were larger, less compact, and of different cellular composition from those of control groups. They contained increased numbers of eosinophils, together with numerous multinucleated giant cells. The effects observed in the anti-IFN-gamma mAb-treated mice, together with the maintenance of MHC class II expression on alveolar macrophages in these animals, could all be explained by the production of IL-4 and other Th2 cytokines. Thus, neutralization of IFN-gamma during challenge responses may shift the Th balance towards domination by the Th2 subset. PMID- 1431136 TI - IL-4 influences IL-2 production and granulomatous inflammation in murine schistosomiasis mansoni. AB - In previous studies the dynamics of IL-2 production by splenic cells of Schistosoma mansoni infected mice was correlated with the intensity of hepatic granulomatous inflammation. To extend those observations, the present studies examined the role of IL-4 on the immune responsiveness of infected mice. The dynamics of IL-4 production by soluble egg Ag-stimulated splenic cells was similar to that of IL-2: minimal levels at the pre-oviposition or early worm egg deposition stages (4 to 6 wk) peak production coincident with maximal granulomatous response (8 wk) followed by a concurrent decline at the chronic stage (18 to 20 wk) in both parameters. Addition of murine rIL-4 to splenocyte cultures of acutely or chronically infected mice did not significantly enhance the soluble egg Ag-elicited proliferative response. Daily injections of rIL-4 (10 to 1000 U) given for 14 days to groups of mice with acute infection, at the high dose-enhanced IL-2, but not IL-4, production. Similar treatment given to chronically infected mice did not augment diminished lymphokine production. Chronically infected mice treated with 10 to 1000 U of rIL-4 showed significantly enhanced liver granulomatous responses compared with untreated animals and the augmented granulomas contained more enlarged macrophages and connective tissue matrix. Repeated injections of anti-IL-4 mAb (11B11) given to acutely infected mice significantly suppressed splenic cell proliferation, IL-2 and IL-4 production, and hepatic granulomatous inflammation. Similar treatment given to chronically infected mice also diminished the down-modulated granulomatous response. These data demonstrate that IL-4 plays an important role in the egg directed granulomatous response and participates in the regulation of Ag-specific lymphoproliferation, and IL-2 and IL-4 production during the course of the infection. PMID- 1431137 TI - Priming of human eosinophils by platelet-activating factor enhances the number of cells able to bind and respond to opsonized particles. AB - Addition of platelet-activating factor (PAF) to human eosinophils leads to the modulation of eosinophil responses. Earlier work from our laboratory has shown that the respiratory burst and homotypic aggregation response in these cells induced by opsonized particles (serum-treated zymosan, STZ), is strongly enhanced after pretreatment (priming) with PAF. In the present study we have investigated the effect of PAF on the binding of fluorescent STZ particles to human eosinophils. Addition of STZ to eosinophils isolated from the peripheral blood of normal donors results in an interaction of the STZ particles with only 30 to 40% of the cells. Treatment of the eosinophils with PAF (1 microM) for 2 min strongly enhanced the rate of particle binding and also doubled the percentage of eosinophils binding STZ. The effect of PAF priming is most likely mediated by a change in CR3, because it is reversed by mAb B2.12 blocking the iC3b binding site of CR3 and unaffected by mAb IV.3 blocking Fc gamma RII. This change is not an increase in cell surface expression of CR3, and it requires an active cellular metabolism to be maintained. The functional consequences of the effect of PAF on STZ binding were investigated in the nitro-blue tetrazolium dye slide test. PAF priming strongly enhanced the percentage of eosinophils producing oxygen radicals after STZ stimulation. Our findings indicate that the priming phenomenon observed in human eosinophils consists, at least in part, of a recruitment of cells able to interact with and to respond to opsonized particles. PMID- 1431138 TI - Plasminogen activator in granulocyte-macrophage-CSF transgenic mice. AB - The pattern of expression of urokinase type plasminogen activator (PA) in granulocyte-macrophage-CSF transgenic mice and their normal littermates was studied using RNAse protection assays and a plasminogen-dependent fibrinolytic assay for PA. Urokinase type PA mRNA was expressed at a high level in transgenic peritoneal cells and at a lower level in transgenic eye tissue and spleen, but not in equivalent tissue from the normal mice. Enzymically active PA was detectable in protein extracts from peritoneal cells taken from transgenic mice of less than 8 wk of age (young mice) but not from normals. Paradoxically, extracts from transgenic mice of more than 12 wk of age (old mice) showed little detectable PA activity despite continuing transcription in some mice of this age. The production of PA by peritoneal cells may be responsible for the spontaneous i.p. bleeding which is a feature of the transgenic mice and production in other tissues may help explain the local pathologic changes. PMID- 1431139 TI - Human endothelial cells are target for platelet-activating factor. II. Platelet activating factor induces platelet-activating factor synthesis in human umbilical vein endothelial cells. AB - Platelet-activating factor (PAF), a phospholipid mediator with broad and potent biologic activities, is synthesized by several inflammatory cells including endothelial cells (EC). PAF is also an effective stimulating agent for EC leading to increased cell permeability and adhesivity. We examined the synthesis of PAF in human umbilical cord vein EC after stimulation of EC with PAF or with its nonmetabolizable analog 1-O-alkyl-2-N-methyl-carbamyl-sn-glycero-3-phosphocholine (C-PAF). PAF (1 to 100 nM) induced a dose- and time-dependent increase of PAF synthesis as detected by [3H]acetate incorporation into PAF fraction. Stimulation of PAF synthesis occurred via activation of the "remodeling pathway" as the 1-O alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF):acetyl-CoA acetyltransferase was dose-dependently increased after PAF treatment. The de novo pathway of PAF synthesis was not activated under these conditions. C-PAF was able to mimic the effect of authentic PAF on [3H] acetate incorporation. The inactive metabolite lyso-PAF (100 nM) had no influence on PAF synthesis in EC. CV-3988, BN 52021, and WEB 2086, potent and specific antagonists of PAF suppressed PAF effects on the remodeling pathway completely. The PAF- and C-PAF-induced [3H]PAF remained 93% cell-associated and was not degraded up to 10 min after stimulation. Characterization of the [3H]acetate-labeled material co-migrating with authentic PAF revealed that a significant proportion (approximately 57%) was actually 1 acyl-2-acetyl-sn-glycero-3-phosphocholine. PAF-induced PAF synthesis might be an important mechanism for amplifying original PAF signals and potentiating adhesive interactions of circulating cells with the endothelium. PMID- 1431140 TI - Serum amyloid P component binds to histones and activates the classical complement pathway. AB - Two members of the pentraxin family of proteins, C-reactive protein (CRP) and serum amyloid P component (SAP), bind to chromatin and may be involved in the solubilization and clearance of nuclear material. Previous studies demonstrated that CRP binding to chromatin is mediated by histones. SAP differs from CRP in being able to bind to DNA, but SAP binding to histones has not been reported. CRP is an activator of the classical C pathway, and C-dependent cleavage of chromatin in the presence of CRP and serum has been shown. Oligomers of SAP have recently been found to bind to C1q and consume total C and C4, indicating that SAP can activate C as well. The present study examined CRP and SAP binding to histones H1 and H2A and C activation after binding. SAP binding to histones H1 and H2A was observed as well as SAP binding to chromatin. In contrast to CRP, SAP binding to chromatin did not require H1. SAP partially inhibited CRP binding to chromatin and to H1. However, neither pentraxin inhibited binding of the other to H2A. Binding of either CRP or SAP to H2A activated C in SAP-depleted serum leading to the deposition of C4 and C3. C activation required C1q and produced C4d indicating that it occurred through the classical pathway. These findings demonstrate that CRP and SAP share histone as well as chromatin binding, and that both pentraxins can activate the classical C pathway after ligand binding. PMID- 1431141 TI - The proteoglycan decorin binds C1q and inhibits the activity of the C1 complex. AB - Decorin, a small collagen-binding dermatan sulfate proteoglycan, is widely distributed as a component of extracellular matrices. Using a solid phase binding assay, we showed that decorin bound C1q at physiologic pH and ionic strength. The interaction did not require divalent cations and was time and temperature dependent reaching equilibrium in 4 h at 37 degrees C. Binding was specific and saturable with an apparent dissociation constant of 7.6 x 10(-9) M. Decorin was shown to bind pepsin-derived fragments containing the collagenous domain of C1q and collagenase-derived fragments containing the globular domain of C1q. Because these fragments share a short sequence of amino acids, this finding suggests that decorin binds to a region of C1q located near the junction of the two domains. Competition studies using purified preparations of the decorin core protein and the glycosaminoglycan chains showed that only the former inhibited binding of decorin to C1q indicating that the interaction is mediated by the decorin core protein. Decorin was shown to inhibit the hemolytic activity of purified C1 as well as C1 in normal human serum. Approximately 50% inhibition was observed at a decorin concentration of 2 micrograms/ml. Inhibition was not observed if C1 was bound to Ag-complexed antibody. Furthermore, neither the core protein nor the glycosaminoglycan chain of decorin inhibited C1, indicating that the intact proteoglycan is necessary for functional activity. PMID- 1431142 TI - Evidence for cross-regulation of Fc gamma RIIIB (CD16) receptor-mediated signaling by Fc gamma RII (CD32) expressed on polymorphonuclear neutrophils. AB - Human polymorphonuclear neutrophils (PMN) express the low affinity receptors for the Fc domain of IgG (Fc gamma R), Fc gamma RII (CD32), and the glycosyl phosphatidylinositol-linked isoform of Fc gamma RIII (Fc gamma RIIIB, CD16) on their cell surface. Both of these receptors have been shown to be signal transducing molecules. However, the mechanisms involved in such signaling are not clearly understood. In this report, we investigated intracellular Ca2+ ([Ca2+]i) signals triggered in PMN by both the receptors using aggregated human IgG (AggIgG) and specific mAb to Fc gamma RII (KuFc79) and Fc gamma RIII (3G8) as ligands. Addition of AggIgG as well as cross-linking of mAb KuFc79 and 3G8 bound to PMN induced [Ca2+]i flux. However, preincubation of PMN with mAb KuFc79 (whole Ig or Fab fragments) in the absence of cross-linking abrogated the [Ca2+]i flux induced by AggIgG and mAb 3G8, indicating that Fc gamma RII receptor occupancy by mAb KuFc79 can block signals mediated by Fc gamma RIIIB. KuFc79-isotype-matched control mAb (MOPC 195) did not abolish the signals generated by AggIgG and mAb 3G8. In addition, mAb KuFc79 did not abrogate [Ca2+]i responses elicited by the receptor for the chemotactic peptide FMLP indicating that modulation of signal transduction by Fc gamma RII-bound KuFc79 is selective for certain receptors. Immunofluorescence analysis of PMN initially treated with mAb KuFc79 followed by AggIgG showed that KuFc79 did not block the binding of AggIgG to PMN. Similarly, competitive binding studies revealed no stearic hindrance between mAb KuFc79 bound to Fc gamma RII and mAb 3G8 bound to Fc gamma RIIIB. Thus, the ability of mAb KuFc79 to modulate signals induced by AggIgG and 3G8 strongly suggests that Fc gamma RII may regulate Fc gamma RIIIB signaling. While previous studies on Fc gamma RII revealed a requirement for cross-linking of the receptor to induce its effector functions, the present study shows that binding of mAb KuFc79 to Fc gamma RII itself, even in a univalent form, results in cross-regulation of Fc gamma RIIIB-triggered signals. Treatment of PMN with protein tyrosine kinase inhibitors, genistein and herbimycin A, abrogated the [Ca2+]i signals elicited by both mAb KuFc79 and 3G8. These results suggest that tyrosine kinase enzyme(s) associated with these receptors may be crucial for positive/negative signals triggered by Fc gamma RII and Fc gamma RIIIB. PMID- 1431143 TI - Intranasal immunization with liposomes containing IL-2 enhances bacterial polysaccharide antigen-specific pulmonary secretory antibody response. AB - Secretory IgA (sIgA) present at mucosal surfaces such as the lungs and intestine plays an important role in resistance to infection occurring at these anatomic sites. Because IL-2 and IL-4 can augment B cell proliferation and Ig production, we investigated possible adjuvant effects of these cytokines on bacterial polysaccharide-specific pulmonary sIgA generation. As shown in previous studies, intranasal immunization with liposomes containing bacterial polysaccharide from Aerobacter levanicum and Pseudomonas aeruginosa resulted in increased numbers of bacterial polysaccharide-specific pulmonary plasma cells and sIgA titers, compared with those found in unimmunized mice. Inclusion of IL-2, but not IL-4, into the intranasally administered liposomes further increased titers of bacterial polysaccharide specific sIgA and pulmonary plasma cells. Intranasal vaccination with liposomes containing bacterial polysaccharide and 10 micrograms/kg IL-2 increased bacterial polysaccharide-specific pulmonary plasma cell numbers by more than 80-fold compared with the response in mice immunized with liposomes containing bacterial polysaccharide, but without IL-2. The percentage of pulmonary plasma cells producing antibody to polysaccharide from A. levanicum rose from 0.14% in mice intranasally immunized with liposomes containing only polysaccharide to 4.1% in animals vaccinated with liposomes containing polysaccharide and IL-2. Intranasal immunization with liposomes containing P. aeruginosa polysaccharide and IL-2 significantly reduced mortality from P. aeruginosa pneumonia. These results demonstrate that IL-2 has potent adjuvant effects on bacterial Ag-specific sIgA production in the lungs when included in intranasally administered liposomes. PMID- 1431144 TI - Effects of cytokines from activated immune cells on vascular cell growth and HIV 1 gene expression. Implications for AIDS-Kaposi's sarcoma pathogenesis. AB - Kaposi's sarcoma (KS) arises more frequently in homosexual and bisexual men than in other groups of HIV-1 infected individuals. Clinico-epidemiologic data indicate that homosexuals often are infected with multiple microbial agents and/or subjected to other antigenic stimuli, preceding or accompanying HIV-1 infection. Signs of immune activation, in fact, frequently have been detected in these individuals, and the onset of KS can precede any sign of immunodeficiency. These data have suggested that products from activated immune cells may affect the development of AIDS-KS. Here we report that conditioned media from activated or dysregulated T cells contain a variety of cytokines that promote the growth of spindle cells derived from KS lesions of AIDS patients (AIDS-KS cells) and induce normal vascular cells, potential cell progenitors of the AIDS-KS cells, to acquire features of the KS cell phenotype ("spindle" cell morphology and growth responsiveness to the mitogenic effect of extracellular HIV-1 Tat protein). The same conditioned media or cytokines promote HIV-1 gene expression and rescue defective HIV-1 proviruses, interrupting HIV-1 latency and increasing Tat production. The cellular and viral effects of cytokines are increased in an additive or synergistic manner by picomolar concentrations of extracellular Tat. These data suggest that cytokines produced by activated immune cells cooperate with HIV-1 infection in AIDS-KS pathogenesis. PMID- 1431145 TI - Influence of the Ig H chain locus on autoantibody production in autoimmune mice. AB - Autoimmune disease is influenced by multiple genes. In this study, we investigated the role of one genetic locus, Ig H chain. IgG2a antichromatin, anti ssDNA, and antihistone autoantibodies (autoAb) from (MRL/Mp-lpr/lpr x C57BL/6 lpr/lpr), (Ighj/b); (C57BL/6-lpr/lpr x C57BL/6-lpr/lpr-Igha), (Ighb/a); and (MRL/Mp-lpr/lpr x MRL/Mp-lpr/lpr-Ighb), (Ighj/b) mice were determined using allotype-specific ELISA. Strikingly, antichromatin and antihistone antibodies (Ab) were comprised of significantly more b allotype than either a or j allotype in all cohorts of F1 mice examined. In mice that produced anti-Sm Ab, the b allotype was used preferentially for these autoAb as well. However, no allotype skewing was observed in IgG2a Ab directed against TNP or DNA, or for total IgG2a. An Igh recombinant locus was utilized to examine the genetic control of b allotype skewing in lpr mice and in chronic graft vs host disease. In both models, the VH region did not appear to be responsible for the preferential use of b allotype. These results indicate a contribution to autoimmunity by the Igh locus and raise the possibility that Ig allotype may influence autoimmune disease by its effect on the production of certain autoAb. PMID- 1431146 TI - The M20 IL-1 inhibitor. I. Purification by preparative isoelectric focusing in free solution. AB - An interleukin-1 (IL-1) inhibitor produced by the M20 myelomonocytic cell line has been shown to be active in various in vitro and in vivo IL-1 induced parameters. This inhibitor has been purified from the conditioned medium by gel filtration through a Sephacryl S-300 column or dye ligand chromatography on Affi Gel blue column, followed by isoelectric focusing in free solution in the pH range 3-5 using the Rotofor cell. When gel filtration by FPLC with the Superose 12 column was used as the final step, the combined sequence of purification procedures resulted in a 1600-fold purification of the IL-1 inhibitor. The purified IL-1 inhibitor has a molecular weight of approximately 52 +/- 4 kDa and a pI of 4.15 +/- 0.1. By SDS-PAGE analysis the inhibitor preparation thus obtained showed the presence of two protein bands, while a few closely spaced protein bands were seen by analytical isoelectric focusing in polyacrylamide gels (pH 3-6). Some of these bands in PAGIF might correspond to different degrees of glycosylation of the inhibitory protein. Although the M20 IL-1 inhibitor has not yet been purified to homogeneity, it should be stressed that the procedures used, allowed us to remove the great majority of the proteins present in the medium in which the M20 cells were cultured, and to recover in satisfactory yield the inhibitor which we consider likely to be present in the conditioned medium in subnanomolar concentrations. PMID- 1431148 TI - A complement-dependent enzyme immunoassay (C-EIA) with increased sensitivity for IgM-rich rabbit sera. AB - An enzyme immunoassay involving activation of complement (C-EIA) was developed for rabbit polyclonal IgM antibodies against lipid A and lipopolysaccharide antigens. C-EIA was significantly higher in sensitivity for IgM-rich rabbit sera compared to EIA using anti-immunoglobulin secondary antibodies. Hence, C-EIA should be useful for the detection of weak IgM reactivities in rabbit sera, especially after short-time immunizations. Selective inhibition of both complement pathways indicated that C-EIA measures activation of the classical pathway. PMID- 1431147 TI - The M20 IL-1 inhibitor. II. Biological characterization. AB - Interleukin-1 (IL-1) is an important mediator in inflammation and immunological processes. The findings of native IL-1 inhibitors suggest a negative feedback mechanism to down-regulate IL-1 mediated acute inflammation. IL-1 inhibitors were also found elevated in disease states associated with high IL-1 levels. We have previously described one such IL-1 inhibitor derived from the human M20 myelomonocytic cell line. In this paper we present several biological and biochemical characteristics of the M20 IL-1 inhibitor. Various in vitro activities of the inhibitor are described and its IL-1 specificity in these assays is demonstrated. Purification of the inhibitor was performed by DEAE-high performance liquid chromatography, isoelectric focusing, gel filtration and dye ligand chromatography column. This protein factor has a MW of 52 +/- 4 kDa and a pI of 4.15 +/- 0.1. The inhibitor has no cross-reactivity against a panel of known cytokines (IL-1 alpha, IL-1 beta, IL-2, sIL-2R, IL-6, tumor necrosis factor (TNF), interferon-gamma (IFN-gamma)) and is distinct from the IL-1 receptor antagonist (IL-1ra). The purified IL-1 inhibitor was destroyed by trypsin, 2 mercaptoethanol, sodium dodecyl sulfate and extremes in pH and in temperature. Only IL-1 induced (but not the IL-2, IL-6 or TNF induced) thymocyte proliferation and PGE2 production by fibroblasts were inhibited by the inhibitor, thus showing specificity to IL-1 in these assays. PMID- 1431149 TI - Capture ELISA for IgM antibodies against Plasmodium falciparum glutamate rich protein. AB - This report describes a novel mu chain capture ELISA for the detection of IgM antibodies against a Plasmodium falciparum antigen. A fragment of the 220 kDa P. falciparum glutamate rich protein containing amino acid residues 489-1271 was expressed in E. coli as a recombinant chimeric beta-galactosidase fusion protein and used as antigen after purification and biotinylation. Specific IgM antibodies were found in 51% (39/77) of sera from adult Liberians immune to malaria. The binding of IgM antibodies was specific for the malaria portion of the fusion protein and no cross-reactivity was found in sera from patients with IgM antibodies due to other diseases. Inhibition studies with a fusion protein containing amino acid residues 816-1134 (GLURP816-1134) representing the carboxy terminal repeat region suggested a different use of epitopes for IgM antibodies in different individuals. PMID- 1431151 TI - Removal of false-positive reactions from plasma in an enzyme immunoassay for bovine interferon-gamma. AB - A monoclonal antibody-based sandwich enzyme immunoassay (EIA) for bovine interferon-gamma (IFN-gamma) has been developed and can be used in conjunction with a whole blood culture system to diagnose tuberculosis in cattle. During its development, normal bovine plasma samples were tested to establish background levels of circulatory IFN-gamma. Of 191 samples tested, 81 (42.4%) were positive (OD > 0.1) when tested undiluted in intact monoclonal antibody (IgG1)-coated wells compared to only 8 (4.2%) in F(ab')2-coated wells, which suggested non specific interference in the EIA rather than circulatory IFN-gamma. Reactivity of all remaining samples was removed by diluting plasmas 1/2 with 1% casein-PBS 0.05% Tween 20 supplemented with an optimum amount (5%) of normal mouse serum (NMS). Serum pools derived from BALB/c, DBA/2, C3H/HeJ, CBA/CaH and Swiss, but not C57BL/6J, mice were found to inhibit equally the reactions of five strong false-positive bovine plasma samples but had no effect on the titre of IFN-gamma in the sample. Sera from other species tested were less effective. This suggests that the interfering factors possess a high degree of specificity, since the immunoglobulin heavy chain of IgG1 produced by all these five strains of mice are allotypically identical and different to IgG1 produced by C57BL/6J mice. The use of F(ab')2 antibody fragments to coat plate wells and sample diluent containing 5% NMS has resulted in an EIA for bovine IFN-gamma that is virtually free from false-positive reactions, has a high degree of reproducibility and a sample detection limit equivalent to approximately 80 pg/ml recombinant bovine IFN gamma. PMID- 1431150 TI - A peroxidase-linked enzyme immunoassay for tumour necrosis factor alpha utilising alternative colorimetric or chemilumimetric substrates. AB - We present a double antibody immunoassay for tumour necrosis factor alpha (TNF alpha) with a peroxidase dependent endpoint which can be detected by absorbance or chemiluminescence depending on the choice of substrate. The chemilumimetric and colorimetric assays have a detection threshold in human serum of 3.9 pg/ml and 7.8 pg/ml respectively and are able to recognise both rTNF alpha and natural TNF alpha. Concentrations of TNF beta, interleukin-1 alpha (IL-1 alpha), IL-beta, IL-2, IL-3, IL-6 or interferon-gamma (IFN-gamma) up to 5 ng/ml failed to show any cross-reactivity. The monoclonal antibody clone 5-2, used in the assays, did not neutralise rTNF alpha in the L929 bioassay. The assay was able to detect rTNF alpha in the presence of excess concentrations of both TNF alpha receptors (p55 and p75). Removal of interference by rheumatoid factor was achieved by the absorbance of the polyclonal antiserum with mouse serum and the inclusion of 10( 2) M dithiothreitol in the buffer containing the TNF alpha polyclonal antiserum. The assay will be useful for the quantitation of endogenous human TNF alpha in serum, other body fluids and culture supernatants, and can also be used to monitor levels of rTNF alpha in clinical trials. PMID- 1431152 TI - Analysis of glycoforms present in two mouse IgG2a monoclonal antibody preparations. AB - Lectins have been used for the determination of the oligosaccharide structures expressed by two monoclonal IgG antibodies, MN12 and RIV6. Dot blot experiments revealed the presence of terminal Fuc alpha (1-->6)GlcNAc, Gal beta (1- >3)GalNAc, Gal beta (1-->4)GlcNAc, Man alpha (1-->6, 1-->3)Man, NeuAc alpha (2- >6)Gal and NeuAc alpha (2-->6)GalNAc on both monoclonal antibodies. MN12 was shown to contain a carbohydrate moiety within the Fc region only. RIV6 contained carbohydrate moieties within both the Fc and Fab regions. Additional O-glycosidic linked carbohydrate chains were detected within the Fc region of both monoclonal antibodies. High mannose structures were also detected on both Mabs. PMID- 1431153 TI - An antibody capture bioassay (ACB) for DNase in human serum samples. AB - A novel assay for antibody captured bioactivity (ACB) has been developed to quantitate deoxyribonuclease I (DNase) in human serum samples. The procedure is simple, sensitive, reproducible and has a high throughput. Serum samples are diluted a minimum of 1/4 and assayed in 96-well microtiter plates coated with polyclonal antibodies specific to DNase. The serum is removed from the wells, the plates are washed and the antibody bound DNase is incubated at 37 degrees C with a DNA-methyl green substrate. The assay is sensitive to 0.8 ng/ml with a range to 10 +/- 2 ng/ml, depending upon the time of incubation (48 +/- 2 h). The recovery of rhDNase spiked into human serum samples averaged 84.4% +/- 6.7% in sera diluted 1/4 and 97.8% +/- 7.2% at a 1/8 serum dilution. Intra-assay precision ranged from 3.0 to 7.5% coefficient of variation (% CV) and interassay precision ranged from 5.0 to 10.2% CV for spiked serum controls. Endogenous DNase concentrations in 27 normal human sera were found to range from < 2.0 to 11.4 ng/ml. Endogenous DNase-like activity was found in Cynomolgus and Rhesus monkey sera; this activity diluted linearly and did not interfere with accurate quantitation of added rh DNase. No endogenous DNase-like activity could be detected in ten Sprague-Dawley rat sera. Bovine pancreatic DNase was found to have only very low cross-reactivity in this assay system. The ACB assay format can potentially be applied to the quantitation of other enzymes in serum and other biological samples. PMID- 1431154 TI - Flow cytometric analysis of transport activity in lymphocytes electroporated with a fluorescent organic anion dye. AB - Organic anion transport in polarized epithelia and macrophages has previously been studied by monitoring the efflux of fluorescent organic anion dyes from cells. We adapted this strategy to the study organic anion transport in lymphocytes. Cloned lymphoma cells and normal and activated human T cells were loaded with a membrane-impermeant, organic anion dye (Lucifer Yellow) by electroporation. Dye efflux in lymphocytes was rapid, energy-dependent, and inhibitable by organic anion transporter inhibitors. Dye efflux could not be attributed to the effects of electroporation. In addition, electroporated, dye loaded T helper cells retained the ability to properly respond to specific antigen. Thus, dye loss occurred in viable, functionally competent cells. These experiments demonstrate that electroporation is an effective means of loading cells with Lucifer Yellow, and that lymphocytes possess organic anion transporters that are functionally similar to those previously described for secretory epithelia and macrophages. PMID- 1431155 TI - Use of the lipid emulsion system and Salmonella typhimurium mitogen adjuvant to stimulate IgG production in chickens. AB - Chickens were immunized with the lipid emulsion system and Salmonella typhimurium mitogen adjuvant for fowl plus synthetic peptides corresponding to the divergent amino acid sequences at the carboxyl terminus of each of two different alpha tubulin isoforms from Arabidopsis thaliana. Antibodies were extracted from egg yolks and used in immunoblot assays to determine the time course of antibody production in two chickens. Specific immunoglobulin production increased 10-14 days after the primary injection in both chickens and reached peak levels shortly thereafter. Booster injections helped maintain IgG production, which eventually dropped off after the final injection. PMID- 1431156 TI - A rapid and sensitive fluorometric microassay for determining cell mediated cytotoxicity to adherent growing cell lines. AB - In order to measure cell mediated cytotoxicity to adherent growing cell lines in vitro more rapidly and conveniently, a fluorometric microassay was developed and results were compared with those obtained by the 51Cr release assay. The fluorometric method is based on the hydrolysis of the fluorochrome 4 methylumbelliferyl heptanoate (MUH) by intracellular esterases of viable cells. Melanoma cell monolayers were incubated with lymphokine activated killer (LAK) cells for 4 h at various effector: target (E:T) cell ratios (E:T = 16, 8, 4, 2:1). Thereafter surviving adherent melanoma cells were stained with MUH for 30 min and fluorescence was measured directly in a 96 well plate reader. For the calculation of LAK cell cytotoxicity fluorescence values were corrected for the number of nonspecifically detached tumor cells during the washes and the number of nonspecifically adherent LAK cells. Using identical target and effector cell preparations both assays showed a nearly proportional increase of percentage cytotoxicity with rising numbers of lymphocytes. Compared with the 51Cr release assay, however, higher cytotoxicity values were obtained with the fluorometric MUH microassay: 57% with MUH versus 26% with 51Cr and 39% versus 14% for cell lines StML-11 and SKMel-28, respectively (E:T ratio = 16:1). The higher cytotoxicity rates obtained with the fluorometric MUH microassay were not due to the additional 30 min staining with MUH or due to nonspecific hydrolysis of MUH by extracellular esterases released from damaged cells, as could be shown by a series of experiments. In conclusion, a simple and rapid fluorometric microassay has been developed showing reliable reproducibility and a higher sensitivity compared with the 51Cr release assay for the determination of cellular cytotoxicity to adherent growing cell lines, avoiding hazardous radioactive labels. PMID- 1431157 TI - An ELISA sandwich capture assay for recombinant fusion proteins containing glutathione-S-transferase. AB - A sandwich capture ELISA technique is presented for detection of recombinant proteins sharing a common affinity domain or reagents such as antibodies that bind to these proteins. An activated carrier protein (BSA) is modified with reduced glutathione (GT), forming an affinity capture reagent for glutathione-S transferase (GST) and recombinant fusion proteins bearing the GST moiety. GT-BSA is immobilized on microtiter plates, and a sandwich is formed consisting of the recombinant fusion protein, reactive antibodies, and detection antibodies. An example is given that demonstrates that this format yields equivalent results to a conventional ELISA test with a panel of newly diagnosed diabetic sera reacting with an islet cell autoantigen. PMID- 1431158 TI - Quantitation and phenotyping of T cell clones by flow cytometry. AB - In order to efficiently analyze large numbers of T cell clones, a method for analysis of small cell cultures by flow cytometry was developed. The aim was to assess cloning efficiency, growth rate and phenotype of T cell clones. The reliability of the flow cytometer for quantitation of cell populations was documented by repeated analysis of manually counted cell samples. In the concentration range from 3000 to 195,000 cells/ml, the correlation coefficient between counts obtained by the flow cytometer and manual cell counts was 0.999 and within-assay coefficients of variation were below 4%. Cell cultures containing less than 200 cells were reliably quantified. The technique was applied for analysis of T cell clonings with different mitogens and in the presence of varying amounts of serum. To reduce time and labour, the cultures were analyzed only 10 days after cloning, when the clones contained less than 100,000 cells. The sensitivity of the flow cytometer in the detection of immunolabeled cells made further expansion of cell cultures unnecessary, thus greatly reducing manual labour and experiment turnover time. The commonly used mitogens phytohemagglutinin (PHA) and the antibody OKT3 resulted in comparable cloning efficiencies and clone sizes. Human serum was essential for high cloning efficiency as well as for continued growth, and could not be substituted with an increased amount of fetal calf serum. When cloning with interleukin-2 at 20,000 U/ml, two growing cell types were identified. The majority of the clones contained CD3+, CD4+, or CD8+ T cells. Ten out of 60 cultures however, contained cells with the CD3-16/56+ NK cell phenotype, indicating that the culture conditions stimulated proliferation of two different cell types. The described method can be applied for rational analysis of large numbers of minute cell cultures, in for example evaluation of different cloning conditions and estimation of precursor cell frequencies in limiting dilution analysis. The simultaneous phenotyping allows precursor cell analysis under conditions that stimulate growth of more than one cell type. PMID- 1431159 TI - Detection of intracellular interleukin-10 by flow cytometry. AB - Detection of cytokines is limited to measurements of the secreted molecule. To circumvent this problem we permeabilized the cell membrane with digitonin and localize cytokine expression using antibodies by flow cytometry. In this report we demonstrate that we can detect specific intracellular interleukin-10 (IL-10) in the HT-2 T cell line only after membrane permeabilization. With this technique intracellular cytokines are readily detectable. PMID- 1431160 TI - Blood B cell subpopulations. The effect of narrow versus wide forward scatter x side scatter gating. PMID- 1431161 TI - A microplate assay for the detection of oxidative products using 2',7' dichlorofluorescin-diacetate. AB - A fluorometric microplate assay was established for the detection of respiratory burst activity in phagocytic cells by assessing oxidation of 2',7' dichlorofluorescin-diacetate (DCFH-DA). This method is based on flow cytometric studies by Bass et al. (J. Immunol. 130 (1983) p. 1910) describing intracellular detection of DCFH oxidation due to the presence of hydrogen peroxides. In the present study we have adapted the assay for use in microtiter plates to determine the amount of extracellular reactive oxidative products. DCFH-DA, granulocytes and stimuli (phorbol myristate acetate, n-formyl-methionyl-leucylphenylalanine, concanavalin A) were added to microtiter plates and after incubation at 37 degrees C, the development of fluorescence intensity was read in a fluorescence concentration analyzer (FCA, Baxter). Calibration of fluorescence units recorded by the FCA was achieved by comparison with defined amounts of fluorescent DCF. The change in measured fluorescence was linear with cell density over the range of 2 x 10(5)-1 x 10(6) cells/well. Cumulative DCF generation in individual wells could be recorded non-destructively at frequent intervals for time course measurements. Results from FCA measurements correlated perfectly with the FACS analysis of the same samples (r = 0.99). In conclusion, this assay can be useful for screening monoclonal antibodies recognizing cell surface structures possibly involved in signal transduction as well as for testing phagocytes for their capacity to release reactive oxidative intermediates. PMID- 1431162 TI - Direct visualisation and quantification of cellular cytotoxicity using two colour flourescence. AB - A fluorescence method is described for the evaluation of cell death induced by cellular cytolytic activity. A green fluorescent membrane dye, D275, was used to label various target cell lines and propidium iodide (PI) uptake was used to assay cell death. Natural killer (NK), lymphokine activated killer (LAK) as well as targeted T cell mediated cellular cytotoxicity were quantified using the fluorescence method and compared to results obtained with the 51chromium (51Cr) release assay. A good correlation was found after an assay period of 4-8 h indicating that the fluorescence method is a reliable alternative to the 51Cr release assay. PMID- 1431163 TI - Preparation of monoclonal mouse antibodies against two specific eu-melanin related compounds. AB - Two eu-melanin precursors, 6-hydroxy-5-methoxyindole-2-carboxylic acid (HMI2C) and 5,6-dihydroxyindole-2-carboxylic acid (DHI2C) were synthesized and coupled to bovine serum albumin, hemocyanin and polylysine by the combined action of carbodiimide and succinimide. These indole-carrier conjugates served as antigens for the production of specific antibodies against DHI2C and HMI2C in BALB/c mice. The specificity of these antibodies was tested using a combination of affinity chromatography and ELISA procedures. Polyclonal mouse antibodies reacted with the indole-carrier conjugates, but not with the unbound indole compounds. Monoclonal antibodies from two hybridoma cell lines were obtained from a HMI2C-immunized mouse after a fusion with four subclonings. They reacted with free HMI2C and to a lesser extent with unbound DHI2C. One monoclonal showed 50% inhibition in the ELISA test at concentrations of 0.6 mumol.l-1 and 5 mumol.l-1 for HMI2C and DHI2C, respectively. These antibodies did not show any cross-reactivity with nine structurally related compounds and should be valuable reagents for the detection and quantification of HMI2C and other eu-melanin related compounds. PMID- 1431164 TI - Bispecific IgA/IgM antibodies and their use in enzyme immunoassay. AB - Two hybrid hybridomas secreting polymeric bispecific antibodies to human chorionic gonadotropin and calf intestinal alkaline phosphatase were produced by fusion of IgA- and IgM-secreting mouse hybridomas. Both hybrid antibodies were purified from ascitic fluid by size exclusion chromatography. An IgM-like fraction was shown to exhibit bispecific activity. Bispecificity was completely lost following mild reduction and alkylation. Both bispecific antibodies were used to develop a sensitive enzyme immunoassay for hCG. PMID- 1431165 TI - Chicken antibodies: a tool to avoid interference by complement activation in ELISA. AB - MicroELISA plates coated with mammalian IgG will activate the human complement system. It has been shown that this activation of the complement system may interfere in solid-phase immunometric assays, and that there is a difference between IgG from different species and between different IgG subclasses in their ability to activate the human complement system. We have studied the ability of mammalian IgG and avian IgG to activate the human complement system. We show that chicken IgG do not activate the human complement system, and chicken IgG can thus be used in solid-phase immunometric assays to reduce interference by complement activation. PMID- 1431166 TI - Sn-chlorin e6 antibacterial immunoconjugates. An in vitro and in vivo analysis. AB - Monoclonal antibody-Sn-chlorin e6 immunoconjugates were prepared by the site selective covalent modification of the monoclonal oligosaccharide moiety. By carefully controlling the reaction conditions and introducing triethanolamine groups as axial ligands of the Sn moiety, conjugates with in vivo biodistribution properties similar to underivatized IgG were prepared. By varying the reaction conditions, conjugates were reproducibly prepared with a range of photosensitizer to mAb molar ratios from 1.6 to 10. Based on a competitive inhibition radioimmunoassay, conjugates prepared by this method showed selectivity and binding affinity comparable to the unmodified antibody. The immunoconjugates had only slightly lower singlet oxygen yields than that observed with the Sn-chlorin e6 precursor indicating that negligible aggregation or structural modification of the chromophores occurred during the synthesis process. In vitro cell killing experiments demonstrated that all conjugates possessed significant cytotoxic activity. Biodistribution studies in mice showed that conjugates prepared with axial ligands had significant serum retention 24 h after injection while conjugates prepared without the triethanolamine ligand were much more rapidly cleared. In vivo specificity was demonstrated using rats infected with Fisher immunotype I P. aeruginosa at a site in the left posterior thigh muscle. Target to background ratios exceeded 60 at 120 h after conjugate injection of the specific immunoconjugate, compared to a ratio of only 6 for a non-specific mouse IgG conjugate. Biodistribution patterns at 120 h post injection indicate that the conjugates were both biologically active and structurally intact. PMID- 1431167 TI - Infection and injection drug use. PMID- 1431168 TI - Neonatal tetanus estimates of mortality derived from a cluster survey in northern Nigeria. AB - A two-stage cluster survey of deaths from neonatal tetanus (NNT) was carried out in Kano metropolis, Northern Nigeria in order to estimate the mortality from the disease. Estimates of mortality were obtained by three different methods which were compared. According to clinical diagnosis, mortality was 20.6/1000 live births while reports of 4-14 day deaths gave a figure of 11.4/1000 live-births. From information volunteered by informants, it appeared to be only 4.6/1000 live births. NNT accounted for 68% neonatal deaths. The sex-specific mortality rates were 23.4 and 17.9 per 1000 live-births for males and females respectively. There was, however, no significant association between sex and death from neonatal tetanus. The mortality for the first 6 months of recall period was 15.2/1000 live births and 24.2/1000 live-births for the last 6 months. There was also no significant association between recall period and death. In view of the markedly different estimates by the various methods of diagnosis, retrospective clinical diagnosis is suggested for community-based surveys of mortality related to neonatal tetanus. PMID- 1431169 TI - CSF findings in Lyme meningitis. AB - The results of cerebrospinal fluid examination in 59 cases of meningitis caused by Borrelia burgdorferi were analysed and compared with 73 non-Lyme meningitis cases. There was no statistically significant difference in the median cell count of 160 x 10(6)/l in the Lyme meningitis patients and the 150 x 10(6)/l in the non Lyme cases. The protein level was elevated in both patients groups to 0.9 g/l and 0.8 g/l, respectively. The glucose level of 2.9 mmol/l (1.0-6.1) was, however, significantly (P = 0.005) lower in Lyme meningitis than the 3.3 mmol/l (1.6-5.4) in the non-Lyme cases. The most important observation of the study was the finding of a combination of pleocytosis, elevated protein (greater than 0.6 g/l) and low glucose levels (less than 2.1 mmol/l) (considered to be pathognostic for tuberculous meningitis) in six of 59 cases of Lyme meningitis. PMID- 1431170 TI - Cerebral abscess on Merseyside 1980-1988. AB - We report a retrospective study of 62 patients presenting to The Walton Centre for Neurology and Neurosurgery with cerebral abscess in the 8-year period between 1980 and 1988. The study shows that while the incidence of cerebral abscess has not altered from the previous decade, aetiological factors have changed and major developments in the diagnosis and management of the condition have resulted in a marked reduction in the morbidity and mortality associated with brain abscess. PMID- 1431171 TI - Malaria therapy in 452 patients, with special reference to the use of quinine. AB - We investigated the efficacy and toxic potential of antimalarial therapy regimens in 452 malaria patients treated between 1980 and 1990. Drug regimens in 330 non immune travellers were compared with those of 122 semi-immunes with acute malaria; 71% patients acquired their infection in tropical Africa, and the 288 Plasmodium falciparum infections were the most prevalent species. Because of increasing drug resistance or toxicity of chloroquine, pyrimethamine-sulfadoxine and even mefloquine, quinine proved to be the most effective antimalarial against P. falciparum and the only one which did not lead to recrudescences. These occurred in 10% patients after chloroquine and 6% after mefloquine. Cinchonism occurred in 25% of those treated with quinine, but it was fully reversible and never necessitated withdrawal of the drug. We conclude that quinine is highly effective in the treatment of P. falciparum infection and is mandatory if the clinical condition requires a fast-acting blood schizonticide, in cases of hyper parasitaemia and if multi-drug resistance occurs; its use should not be restricted by reversible side-effects such as cinchonism. PMID- 1431172 TI - An infectious disease day care unit--the first year. AB - Details are given of what is believed to be the first Day Care Unit in the U.K. for the diagnosis and treatment of infection and infectious diseases. The reaction of referring doctors and their patients has been favourable, cross infection in the home has not been a problem and some potentially life threatening infections have been diagnosed earlier than might otherwise have been the case. Capital and running costs were relatively small and the use of inpatient beds for infectious diseases became more efficient. PMID- 1431173 TI - Haemophilus influenzae type b purpura fulminans treated with hyperbaric oxygen. AB - We report the case of a 4-month-old child with purpura fulminans caused by Haemophilus influenzae type b. In addition to conventional therapy, she was treated with hyperbaric oxygen, and made a full recovery. Hyperbaric oxygen as an adjunct to other therapy in purpura fulminans is discussed. PMID- 1431174 TI - Fatal disseminated Scedosporium inflatum infection in a neutropenic immunocompromised patient. AB - Disseminated infection with the fungus Scedosporium inflatum in a neutropenic patient with non-Hodgkins lymphoma presented with the triad of muscle tenderness, papular skin lesions and fever, and progressed rapidly to a fatal outcome. This represents the first reported instance of fatal widely disseminated infection with this organism, and demonstrates that the triad of presenting clinical features, formerly reported to be pathognomic of systemic candidiasis, can no longer be regarded as specific for infection with a particular species of yeast or fungus. PMID- 1431175 TI - Recurrent post-infective Henoch-Schonlein syndrome: a genetic influence related to HLA B35? AB - The clinical features, laboratory findings, infection stimuli and HLA phenotypes of five young adults with recurrent episodes of Henoch-Schonlein syndrome (HSS) are reported. We define recurrences as the reappearance of the characteristic purpuric rash and associated symptoms more than 8 weeks after the onset of the original episode of purpura. All patients had documented evidence of a bacterial or viral infection before one or more of the relapses, the periods between which varied from 1 to 13 years. Four of our five patients possessed the HLA B35 phenotype and two of these four patients were also HLA B18 antigen positive. Those with the HLA B35 haplotype had recurrent episodes of purpura with nephritis triggered by minor pharyngeal (viral or bacterial) infections. The HLA B35 haplotype has a frequency of 4% in the indigenous Scottish population and has previously been linked with single episodes of the Henoch-Schonlein syndrome with nephritis in German, Slavic and French patients. It has not previously been related to recurrent episodes of the syndrome. We postulate that patients who are HLA B35 positive may be genetically more susceptible to recurrent episodes of HSS with nephritis, stimulated by a heterogeneous group of infective stimuli and resulting in a protracted illness with significant renal involvement. PMID- 1431176 TI - Metronidazole-resistant Bacteroides fragilis wound infection. AB - We report the isolation of metronidazole-resistant Bacteroides fragilis from a post-operative wound abscess in a 72-year-old woman who had not been treated with metronidazole during the preceding 9 months. The case illustrates the need for caution when identifying anaerobes on the basis of metronidazole sensitivity. PMID- 1431177 TI - Eradication of a multiple drug resistant Salmonella paratyphi A causing meningitis with ciprofloxacin. AB - A previously healthy breast-fed baby was admitted at 10 days of age to a hospital in the north of Pakistan with diarrhoea and fever. He was treated for suspected sepsis with intravenous cefotaxime and tobramycin. Cultures of blood and faeces at that time proved negative. At 12 days of age, seizures began and examination of CSF revealed evidence of pyogenic meningitis but bacteria were neither seen microscopically nor isolated in culture. Ceftazidime was substituted for cefotaxime and carbenicillin was given also. Since the baby's condition continued to deteriorate with persistent fever, vomiting and recurrent seizures, he was transferred to the Aga Khan University Hospital, Karachi. Examination of CSF there confirmed the diagnosis of pyogenic meningitis and revealed Gram-negative bacteria. Cultures of CSF and faeces yielded Salmonella paratyphi A but the blood culture was negative. The isolate was found to be multiple antimicrobially resistant but sensitive to ciprofloxacin. Treatment with this drug was therefore started 3 days after the baby's admission to the Aga Khan Hospital. Within 36 h, improvement was observed. From then onwards, the baby made a progressive recovery and was healthy when seen at 7 months of age. PMID- 1431178 TI - Surveillance of Mycoplasma pneumoniae infections in Scotland 1986-1991. AB - Mycoplasma pneumoniae is the second most common cause of community-acquired pneumonia. Infection is found worldwide and epidemics are said to occur in 4 yearly cycles. In Scotland this pattern has been noted since 1982 and, in common with England and Wales as well probably as other parts of Europe, there is a current epidemic which began in the autumn of 1990. The disease has been noted predominantly in children and young adults, with lower respiratory tract infection as the most common manifestation. At present, diagnosis is based on a serological response and various tests are available for detecting both primary infection and reinfection. In view of the present epidemic, initial treatment of respiratory-tract infection, especially in children and young adults, should include adequate cover against Mycoplasma pneumoniae. PMID- 1431179 TI - Serodiagnosis of cryptosporidiosis in Italian HIV-positive patients by means of an oocyst soluble antigen in an ELISA. AB - A sensitive, specific, and reproducible ELISA which incorporated an oocyst soluble antigen was used in order to detect specific Cryptosporidium immunoglobulins G and M in Italian HIV-positive patients. The soluble antigen was prepared from purified oocysts collected from experimentally infected calves. The serum working dilution was established at 1 in 50. Of parasitologically positive and HIV-positive patients, 95% showed specific IgG or IgM or both in their serum. Of HIV-positive patients, some of whom had diarrhoea of uncertain aetiology, 15.8% were found to have specific IgG. Both specific IgG and IgM were detected in the serum of an HIV-positive patient 1 year before the shedding of oocysts in the faeces. Sixteen (5.3%) of 300 presumed healthy people, positive for specific IgG, were all IgM-negative. Any significant cross-reactions with other parasitic infections were not observed. With a serum dilution greater than 1 in 25, only a low degree of positivity was observed with samples highly IgG-positive for Toxoplasma species. The ELISA showed a higher than expected prevalence of Cryptosporidium infection in Italian HIV-positive patients. PMID- 1431180 TI - Umbilical catheter-related resistant Klebsiella septicaemia in a pre-term infant successfully treated with imipenem via the catheter. PMID- 1431181 TI - A fatal case of pneumococcal cellulitis. PMID- 1431182 TI - [Retrospective study of urethral stricture in the Urology Service at the Ignace Deen Hospital. January 1985--October 1990]. AB - The authors make an etiologic, epidemiologic and therapeutic analysis of 505 urethral strictures treated over a 5 year period. They trig to find a prevention of such affection. PMID- 1431183 TI - [Complete urinary retention secondary to lumbosacral zona]. AB - A case of complete urinary retention related to a HZV neurogenic bladder is reported. Different findings of the disease are discussed, e.g., urodynamics and physiopathology. PMID- 1431184 TI - [Endometrioid adenocarcinoma of the prostate. Apropos of a case, review of the literature]. AB - Endometrioid carcinoma of the prostate is an uncommon form of prostatic cancer. The authors present the case of a 77 year-old man and discuss the different particularities of this rare entity. PMID- 1431185 TI - [Therapeutic embolization of a renal angiomyolipoma associated with tuberous sclerosis]. AB - The authors report about one case of bilateral renal angiomyolipoma, which is interesting because it is associated with tuberous sclerosis and was revealed by chronic anemia, and because of the treatment chosen, which consisted in the selective embolization of the neovessels. Follow-up at one year showed the reduction of the tumoral mass and the proper function of the remaining renal parenchyma. PMID- 1431186 TI - [Oncocytic tumors of the kidney apropos of 2 cases. Actualities in the preoperative diagnosis and therapeutic attitude]. AB - The authors report two cases of renal oncocytoma treated by radical nephrectomy. There is still a controversy because the term oncocytoma is used for all tumors containing oncocytes, either true oncocytoma or adenocarcinoma with oncocytoma cells. The main problem is to distinguish, prior to surgery, between renal oncocytoma, a tumor with benign evolution, and renal adenocarcinoma with oncocytes, to offer conservative surgery for renal oncocytoma. PMID- 1431187 TI - [Morbidity of radical prostatectomy for localized cancer of the prostate. Apropos of 100 cases]. AB - Adenocarcinoma of the prostate is the most frequent cancer of male over 60 years of age. Radical prostatectomy is one of the preferred modes of treatment for localized stages. Surgical morbidity decreases with experience and consists mainly in bleeding and rectal injury. Delayed morbidity comprises loss of erection, anastomosis stricture, incontinence. A retrospective study of 100 patients is reported. PMID- 1431188 TI - [Calculation of prostatic volume by endorectal ultrasonography. A formula of surgical observation]. AB - This study compares ultrasonographic prediction of prostatic volume and surgical exerese. A total of 200 prostates have been measured by the same echographist, operated upon by the same surgeon, and stratified for histology, surgical technique and weight. Adopting the general formula: Surgical volume = D1 x D2 x D3/x the surgical volume is calculated by a simplified and complete definition for a denominator giving the most accurate prediction. CONCLUSIONS: a. the glands of more than 60 cc could be calculated by the classical formula of ellipsoid pi x D1 x D2 x D3/6, simplified to D1 x D2 x D3/2, with a 21% standard deviation error from the surgical volume; b. medium-sized prostates (20-60 cc) could be calculated by the formula: D1 x D2 x D3/3 with a 21% standard deviation; c. prostates smaller than 20 cc, a series which included all reoperations for remnants or recurrence, could be calculated with the same proposed formula with a 22% standard deviation, while the classical ellipsoid formula led to a 56% standard deviation error. No mathematical formula based only on three prostatic diameters is reliable to assess true parenchymal weight. PMID- 1431189 TI - [Kidney retransplantation: prognostic factors in a series of 84 cases]. AB - Results are presented of a series of 84 patients receiving renal retransplants over the last 12 years. One year survival rate of patients and transplants was 87.6% and 79.1% respectively, compared with 92.5% and 81.2% for the 783 first grafts performed during the same period. Positive prognostic features were the absence of sensitization, survival of the first transplant for more than 6 months, and the inclusion of cyclosporin in the immunodepressive treatment. PMID- 1431190 TI - [Localized transrectal hyperthermia in the treatment of obstructive manifestations of prostatic adenoma. Review of the literature and personal experience]. AB - For about the last 10 years, transrectal hyperthermia has been used to treat obstructive manifestations of adenoma of prostate. This procedure induces interstitial edema and acts preferentially on the fibrous elements of the prostate. Several therapeutic regimens have been used successively by different teams, after objective and subjective inclusion screening programmes. Results published up to the present show about 45% of objective responders (against 3% in a placebo group) with improvement sustained in 3 out of 4 cases. Morbidity rate (infection and urinary retention) was 3%. Data from a retrospective study of a series of personally treated patients was w used to determine those with the greatest chance of a successful outcome, even though this is never comparable with that of surgical treatment. PMID- 1431191 TI - [Treatment of urinary stress incontinence in women by percutaneous cervico cystopexy. Gitte's operation: contribution of intraoperative ultrasonography. Apropos of 47 patients]. AB - Between March 1988 and February 1991, 47 patients with urinary stress incontinence (USI) were treated by Gittes' operation, suspension thread traction being determined by perioperative ultrasonography in 31 of these cases. All patients were re-examined on February 1992 after a mean follow-up of 26 months (range 12 to 24 mths). The global success rate (recovery and improvement) was assessed as 72% at 3 months and 56% at follow-up. Rated as a function of closure pressure (CP), the success rate at evaluation was 62% with normal CP, 42% with CP low for age, and 33% with CP < 30 cm H20. For the 31 patients with perioperative ultrasonography examination the success rate was 80% at 3 months and 70% at follow up. As a function of CP the rate was 83% at follow up with a normal CP, 50% with a CP low for age, 37.5% with a CP < 30 cm H20. Although Gittes' operation is a simple, fairly non-aggressive intervention, results diverge widely from those obtained with "classical" techniques. Optimization of indications is essential, therefore, only patients with pure USI without hypotonia of the sphincter obtaining maximum benefit from the intervention, carried out preferably under perioperative by control ultrasonography. PMID- 1431192 TI - Rowatinex for the treatment of ureterolithiasis. AB - A prospective, randomized, double-blind study was performed on 87 patients with ureterolithiasis, assessing the effect of the essential oil preparation Rowatinex (Rowa Pharmaceuticals, Ireland) for the treatment of ureterolithiasis. Forty three patients were treated with Rowatinex and 44 patients with placebo. Despite the larger average diameter of calculi in the group of patients treated with Rowatinex, the overall stone expulsion rate was significantly higher in the Rowatinex group as compared to placebo: 81% and 59%, respectively (0.025 > p > 0.01). This higher rate of stone expulsion is observed in patients with disappearance of pretreatment ureteral dilatation (when patients with expelled stones are excluded) (0.05 > p > 0.001). Seven patients in the Rowatinex group had mild to moderate gastrointestinal disturbances; no other significant side effects were noted during the treatment in either group. We conclude that early treatment with Rowatinex for patients with ureteral stones is indicated before other more aggressive measures are considered. PMID- 1431193 TI - Biotic and abiotic parameters associated with an epizootic of Coelomomyces punctatus in a larval population of the mosquito Anopheles quadrimaculatus. AB - Biotic and abiotic parameters associated with an epizootic of the fungus Coelomomyces punctatus in larval populations of the mosquito Anopheles quadrimaculatus were investigated for three mosquito breeding seasons (1986-1988) in two adjacent farm ponds in North Carolina. In the first pond, the prevalence of infected larvae averaged 42% (range 0-85%) for collections made weekly from May 1 to November 20, 1986, but larvae did not occur in this pond in 1987. Infection rates in the adjacent pond, sampled during the mosquito breeding seasons of 1987 and 1988, declined from 10.9% (range 0-27.5%) in 1987 to 2.5% (range 0-14.2%) in 1988. Correlation analyses between the number of female copepods and fungal infection rates in sentinel mosquitoes were significant (P < 0.01) for Acanthocyclops robustus but insignificant for eight other species. Infections obtained in sentinel larvae placed in the ponds for 3 hr intervals indicated that C. punctatus infected larvae around sundown. Infection rates for field-collected larvae increased with the stage of larval development. However, experiments with sentinel larvae showed that early instars were more susceptible to infection than later instars, suggesting that the higher infection rates in late instars resulted from individual larvae being infected by two or more zygotes during larval development. Standard multiple regression analyses, used to determine the relationship between seasonal infection rates and water chemistry, weather variables, and the abundance of early and late instar larvae, showed that the abundance of late instars was the only independent variable common to linear models. The models only accounted for 20 and 9% of the variation in larval infection rates for 1987 and 1988, respectively. These results indicate that of the parameters examined, the seasonal abundance of the copepod, A. robustus, was the most important factor (or variable) correlated with the prevalence of mosquito infection. PMID- 1431194 TI - Evidence for the copepods Acanthocyclops robustus and Mesocyclops edax as competent intermediate hosts for Coelomomyces punctatus during an epizootic in a larval population of the mosquito Anopheles quadrimaculatus. AB - Field and laboratory experiments were conducted during an epizootic of Coelomomyces punctatus (Chytridiomycetes: Blastocladiales) in a population of the mosquito Anopheles quadrimaculatus in a North Carolina farm pond to examine the interactions of several potential copepod hosts with the mosquito and fungus. The diel vertical migratory behavior of the copepod species Acanthocyclops robustus, Eucyclops serrulatus, Macrocyclops albidus, and Mesocyclops edax were monitored in relation to infection rates in sentinel mosquito larvae. Mosquito infection occurred primarily around dusk, the same period during which A. robustus and E. serrulatus were most abundant near the surface of the pond. However, exposure of A. robustus, E. serrulatus, M. albidus, M. edax, Microcyclops varicans, and Paracyclops poppei to fungal meiospores in the laboratory showed that only A. robustus and M. edax were competent intermediate hosts for C. punctatus. Laboratory studies of the diel periodicity of gametangial dehiscence in A. robustus and M. edax infected with C. punctatus revealed that gamete release and zygote formation also occurred around dusk. The combined results of the laboratory and field studies on copepod abundance, susceptibility to infection, and periodicity of gametangial dehiscence suggest that A. robustus was the principal intermediate host for C. punctatus during the epizootic, though it is probable that M. edax also contributed importantly to the overall rate of larval infection. PMID- 1431195 TI - Influence of temperature on developmental parameters of the parasite/host system Edhazardia aedis (Microsporida: Amblyosporidae) and Aedes aegypti (Diptera: Culicidae). AB - Larvae of Aedes aegypti, transovarially infected with Edhazardia aedis, were reared between 20 and 36 degrees C to determine the influence of temperature on the development of the parasite and the infected host. Development of the parasite was evaluated based on spore yield and size. The predicted optimum temperature for maximum spore production of E. aedis in A. aegypti was 30.8 degrees C. The results demonstrate that the E. aedis-A. aegypti system has a wide temperature tolerance; whereas spore yield will be lower at unfavorable temperatures, the host will remain infected. Additionally, spores were significantly smaller from individual reared at 34 degrees C than those reared at either 20 or 27 degrees C. Development of the infected host was evaluated based on pupal weight and time of pupation. Infected pupae were significantly larger than uninfected pupae. There was also a significant difference in the pupation rate between controls and infected A. aegypti larvae. Controls had a 50% cumulative pupation time (CPT50) of 65.7 degree days and infected individuals a CPT50 of 76.6 degree days. PMID- 1431196 TI - Expression of the high-affinity receptor for IgE (Fc epsilon RI) on human Langerhans cells: the end of a dogma. PMID- 1431197 TI - Effect of donor Langerhans cells on corneal graft rejection. AB - Unlike other cutaneous surfaces, the central portion of the corneal epithelium is typically devoid of Langerhans cells. The absence of Ia+ Langerhans cells in the central cornea is of more than casual interest and may explain the immunologic privilege that is characteristic of corneal allografts. The present communication summarizes previous studies that examined the role of corneal Langerhans cells in eliciting alloimmune responses and corneal graft rejection in rodents. Under normal circumstances, corneal allografts are poorly immunogenic when residing in the avascular ocular graft bed even though the graft displays large quantities of alloantigens. The afferent blockade of the immune response can be circumvented by donor-derived Langerhans cells that serve as potent immunogens for all categories of corneal allografts except grafts involving allodisparity only at class I major histocompatibility complex loci. Thus, the presence of donor-derived Langerhans cells exerts profound effects on the fate of corneal allografts. PMID- 1431198 TI - Langerhans cells, antigen presentation, and the diversity of responses to chemical allergens. AB - Respiratory and contact chemical allergens provoke differential immune responses in mice, stimulating preferentially T helper-2 (TH2) and TH1 cells, respectively. In an attempt to discover whether such differences are effected at the level of antigen handling and presentation we have examined the effect of topical exposure to trimellitic anhydride (TMA), a respiratory allergen, and 2,4 dinitrochlorobenzene (DNCB), a contact allergen, on Langerhans cell (LC) MHC class II (Ia) expression. Neither chemical caused a significant change in LC size. As measured by analytical flow cytometry, exposure to DNCB resulted in a time-dependent increase in LC Ia expression that exceeded 160% of control values within 24 h. Exposure to concentrations of TMA that caused an equivalent activation of draining lymph nodes failed to affect Ia expression by LC. Application of sodium lauryl sulfate at concentrations that caused edema also failed to influence LC Ia. These data demonstrate that TMA and DNCB exert differential effects on epidermal LC, possibly indicative of differences in antigen handling. PMID- 1431199 TI - Studies on human skin lymph containing Langerhans cells from sodium lauryl sulphate contact dermatitis. AB - Immunologic processes in diseased human skin have been extensively investigated, but little is known about the effect of skin diseases on human afferent skin lymph. Starting in the papillary dermis, the skin lymphatics drain the adjacent tissue in a one-way flow toward the regional lymph nodes. The composition of the afferent lymph, therefore, reflects the immunologic inflammatory processes in the drained tissue. To obtain afferent lymph to investigate its content, we inserted a cannula, by means of microsurgery, into a superficial peripheral lymph vessel draining a defined skin area. By manipulating the drained skin area and subsequent examination of the lymph we established an in vivo system for investigating the kinetics of lymph changes during the course of skin reactions. In lymph derived from a mild sodium lauryl sulphate (SLS)--induced contact dermatitis we could demonstrate an increase of both flow and cells. In particular, the number of Langerhans cells (LC) increased enormously during the course of the skin reaction. It, therefore, seems that a large increase in the migration of LC from the skin to the regional lymph nodes is a major feature of SLS-induced contact dermatitis, suggesting that LC may play a major role in the irritant contact dermatitis reaction. PMID- 1431200 TI - Human epidermal Langerhans cells express beta 1 integrins that mediate their adhesion to laminin and fibronectin. AB - Members of the beta 1 or very late antigen (VLA) integrin family represent the predominant class of integrin extracellular matrix receptors. Adhesion assays were developed for the identification of the beta 1 integrins involved in the adhesive interactions between Langerhans cells (which mainly express alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1) and extracellular matrix proteins. For this purpose, binding assays were performed on fibronectin-, laminin-, collagen type IV-, and collagen type I-coated plates. 59% +/- 21% of Langerhans cells (LC) specifically attached to fibronectin. Using as inhibitory probes monoclonal antibodies against the beta 1, alpha 5, and alpha 3 chains and the synthetic peptide GRGDSP resulted in a decrease of 43%, 41%, 15%, and 42% respectively of LC binding to fibronectin. 76% +/- 20% of LC specifically adhered to laminin. Anti-alpha 6 monoclonal antibody potently inhibited this adhesion, which dropped to 36%, whereas the synthetic peptide GRGDSP was ineffective. A low number of LC adhered to type I and type IV collagen (13-15%). These results indicate that alpha 5 beta 1 and alpha 6 beta 1 were the major beta 1 integrins involved in LC adhesion to fibronectin and laminin. Ultrastructural cell morphology of adherent cells was examined and showed that LC were largely spread on laminin and became tightly bound to the substrate on a large portion of membrane. On fibronectin surface, the contact between LC and substrate was smaller, thus cells could conserve their general round aspect. Moreover, LC binding to fibronectin and laminin induced a significative decrease of the Birbeck granule number. The finding that LC attach to LM and FN in vitro suggests they exist similarly in vivo. By mediating a passage through basement membrane and migration throughout the fibronectin network of the dermis, alpha 5 beta 1 and alpha 6 beta 1 could contribute to the ability of LC to migrate into and out of the epidermis. PMID- 1431201 TI - Release of soluble Fc gamma RII/CD32 molecules by human Langerhans cells: a subtle balance between shedding and secretion? AB - Freshly isolated human Langerhans cells (LC) express two forms of Fc gamma RII: a membrane-associated form detected by monoclonal antibody (MoAb) anti-CD32, which recognize an extracytoplasmic epitope of the molecule, and a soluble secreted form, whose existence is suggested by reverse transcriptase-polymerase chain reaction (RT-PCR) experiments. Indeed, RT-PCR performed on total LC RNA reveals the presence of two Fc gamma RIIA mRNA, one encoding the FC gamma RIIA with a transmembrane region (membranous form) and the other without this region (soluble form). Densitometry studies performed on the two PCR products reveal that the ratio between the membranous form and the soluble secreted form is about 1.5. LC maintained in culture for 24-48 h lose the major part of their membrane Fc gamma RII expression (shown by flow cytometry) and release soluble Fc gamma RII molecules (revealed by dot-blot assay), but maintain the same ratio of the two Fc gamma RIIA mRNA. The disappearance of the membrane-associated Fc gamma RII may be explained either by modification of its recycling pathway or by proteolytic cleavage of the receptor at the cell surface. Thus, soluble Fc gamma RII molecules generated during LC culture may result from proteolytic cleavage of the cell-surface receptor and/or secretion of a soluble form derived from the translation of an alternate spliced mRNA. Interestingly, addition of TNF-alpha (10 ng/ml) to the culture medium i) maintains the expression of the membranous form, which can be detected on the LC surface at the same level as on freshly isolated LC, and ii) reverses the ratio (to 0.6) of the two Fc gamma RII mRNA, the mRNA encoding the soluble form becoming predominant. Thus, TNF-alpha seems to modify the expression of the Fc gamma RII at the mRNA level, favoring the secretion of soluble Fc gamma RII molecules, and changes the fate of the membranous Fc gamma RII. PMID- 1431202 TI - Membrane ecto-ATPase on epidermal Langerhans cells. AB - Epidermal Langerhans cells (LC) possess a plasma membrane Mg(++)- or Ca(++) dependent ecto-ATPase (mATPase), the function of which is not known. On the other hand, extracellular ATP (ATPo) has been shown to cause a rapid increase in cell membrane permeability for selected cells, thus inducing the entry of exogenous substances, leading eventually to cell death. ATPo has also been shown to be a mediator of T cell-mediated cytotoxicity. We have observed human LC to be resistant to the permeabilizing effects of ATPo when compared to cultured human keratinocytes and J774 macrophages. In addition, our preliminary evidence in vitro suggests that mATPase on LC may provide protection against the lytic effects of ATPo. Finally, we propose that this latter mechanism may also operate in vivo. PMID- 1431203 TI - Characteristics of antigen-presenting cells involved in contact sensitization of normal and UV-irradiated mice. AB - Exposure of mice to ultraviolet (UV)-B (280-320 nm) radiation alters their immune response to contact-sensitizing haptens applied to UV-irradiated skin. Under these conditions, the contact-hypersensitivity response is reduced, and hapten specific suppressor T lymphocytes can be found in the spleen. Considerable evidence suggests that the epidermal Langerhans cell is one of the principal targets of this effect of UV irradiation that leads, ultimately, to suppressor cell formation. We are using a combination of cell-surface markers and light and electron microscopy to determine whether differences can be detected in the antigen-presenting cells involved in contact sensitization of normal and UV irradiated mice. PMID- 1431205 TI - Fc epsilon RI mediates IgE binding to human epidermal Langerhans cells. AB - In a recent series of experiments, we observed that epidermal Langerhans cells (LC) of healthy, non-atopic individuals have the capacity of specifically binding monomeric serum or myeloma IgE. IgE-binding to LC could neither be prevented by pre-incubation of the cryostat sections with monoclonal antibodies (MoAb) against either Fc epsilon RII/CD23 or Fc gamma RII/CD32 nor by the addition of excess amounts of lactose, but could be entirely abrogated by pre-incubation with the anti-Fc epsilon RI MoAb 15-1. A direct testing of the anti-Fc epsilon RI MoAb 15 1 and 19-1 on cryostat sections in an indirect immuno-double-labeling technique showed that, in contrast to eight different anti-Fc epsilon RII/CD23 MoAb, these MoAb react with the majority of CD1a-bearing epidermal cells. At an ultrastructural level, 15-1 immunogold-labeling in the epidermis was confined to the surface of cells exhibiting Birbeck granules. In further experiments, we were able to amplify by polymerase chain reaction (PCR) technology transcripts for the alpha, beta, and gamma chains of Fc epsilon RI from LC-enriched epidermal cells and dermal cells, but not from LC-depleted epidermal cells. Transcripts for the mast cell enzyme tryptase were exclusively found in dermal cell-derived RNA preparations, thus excluding a contamination of the LC-enriched epidermal cell preparations by dermal mast cells. Collectively, these data show that epidermal LC, but not other epidermal cells, express Fc epsilon RI molecules. PMID- 1431206 TI - Development and function of dendritic cells in health and disease. AB - The life history of dendritic cells (DC) is now established from their origins from bone marrow stem cells, their distribution through blood to the tissues, and their movement via afferent lymph to lymph nodes for the initiation of immune responses. Bone-marrow stem cells, and occasional stem cells in peripheral blood (about 1 per 10(5) mononuclear cells), can give rise both to DC and macrophages (MO). In addition to stem cells in blood, after short-term culture of mononuclear cells, three major morphologic types of DC can be separated (types I-III), which probably represent the maturational pathway of this cell type; type II cells resemble tissue DC such as Langerhans cells and type III have a veiled morphology similar to that seen in cells of afferent lymph and in the interdigitating cells of the paracortex of lymph nodes. Functionally, DC cultured from peripheral blood are able to acquire large antigens and process them like Langerhans cells of the skin. They can also present antigens to stimulate primary T-cell responses, a property associated with lymph node DC. In tissues, DC appear to act as outposts of the immune system, acquire antigens, and, particularly in primary responses, carry the antigens to lymph nodes where they initiate T-cell responses. In secondary responses, activation of memory T cells in the periphery and the acquisition of antigen/antibody complexes by follicular dendritic cells of the lymph node follicles, which stimulate B cell memory, may be more important pathways for immune activation. DC may play a role in the development of many immunologic diseases including cancer, autoimmunity, and acquired immunodeficiency syndrome (AIDS). PMID- 1431204 TI - Alpha IIB beta 3 integrin dissociation induced by EDTA results in formation of Birbeck granule-like structures in human blood platelets. AB - EDTA (5 mM at 37 degrees C and pH 7.4 for 30 min) induces morphologic changes in the platelet surface-connected canalicular system (SCCS), in particular the collapse of some portions of the canaliculi. These collapsed elements are made up of two parallel limiting membranes and a central irregular striated zone, a pentalaminar organization that clearly resembles that of Langerhans cell Birbeck granules (BG). Such BG-like structures are also seen between adjacent platelets in EDTA-treated platelet microaggregates. EDTA is known to induce an irreversible dissociation of the platelet membrane glycoprotein(GP)IIb-IIIa, the alpha IIb beta 3 platelet-specific intergrin, a calcium-dependent heterodimer that serves as an inducible receptor for fibrinogen and is essential for platelet aggregation. Hence, we looked for involvement of the GPIIb-IIIa in the formation of these BG-like modifications. We observed that these changes i) cannot be induced in type I Glanzmann's thrombasthenia, where the GPIIb-IIIa complexes are absent; ii) did not appear when human platelets were pre-incubated with MoAb anti GPIIb-IIIa complex, which protected GPIIb-IIIa from EDTA-induced dissociation; iii) appeared only at alkaline pH and 37 degrees C, which corresponds to the range of pH and temperature where EDTA can dissociate the GPIIb-IIIa complexes; iv) are accompanied by the dissappearance on fluorescence flow cytometry analysis of the heterodimer specific epitopes; and v) do not appear in rat platelets at pH 7.4 where GPIIb-IIIa does not dissociate after EDTA treatment. Thus, the appearance of BG-like structures in the platelet SCCS is directly dependent on the EDTA-induced dissociation of the GPIIb-IIIa complexes. Furthermore, using gold-labeled MoAb concomitantly with the addition of EDTA, we observed that only GPIIb is present in the collapsed portions of the canaliculi. On Lowicryl thin sections essentially polyclonal antibodies to GPIIb labeled the central striated zone. All these observations lead us to suggest that homopolymers of GPIIb could be responsible for "zipping" of the SCCS and raise the question of the participation of a Langerhans cell integrin in the formation of Langerhans cell BG. PMID- 1431207 TI - Cytokine expression by epidermal cell subpopulations. AB - Epidermal cells (EC) are a rich source of cytokines that can regulate the function of cells in skin and in other tissues. To organize the array of data pertaining to cytokine expression by EC subpopulations, we have tabulated such data according to cell source, state of cell activation, and type of assay employed. This information forms a background for our own studies, in which reverse transcriptase-polymerase chain reaction (RT-PCR) was used to show that Langerhans cells (LC) are the principal source of mRNA for interleukin 1 beta and macrophage inflammatory protein-1 alpha (MIP-1 alpha) among unstimulated mouse EC. PMID- 1431208 TI - Differentiation of epidermal Langerhans cells in macrophage colony-stimulating factor-deficient mice homozygous for the osteopetrosis (op) mutation. AB - The osteopetrosis (op) mutation is within the gene for macrophage colony stimulating factor (M-CSF). Homozygotes (op/op) lack M-CSF activity and show abnormalities in the differentiation of osteoclasts and other cells within the macrophage lineage. The effect of the op mutation on the development of Langerhans cells (LC) was determined in order to assess differentiation of such cells in vivo in the absence of M-CSF. (C57BL/6J X C3HeB/FeJ)F2-op/op and +/? Littermate control mice were raised from +/? breeders obtained from the Jackson Laboratory. The mice were killed with ether anesthesia at 4 weeks after birth and skin specimens were excised and examined by immunohistochemistry using anti-mouse pan macrophage monoclonal antibodies (MoAb), F4/80 and BM8; anti-mouse LC MoAb, NLDC-145, M1-8, and MIDC8; and anti-mouse Ia MoAb, M5/114. In epidermal sheets, numbers of LC were counted. Histochemical staining of adenosine diphosphatase (ADPase) localization was also performed as a marker of LC. Epidermal LC from op/op mice showed reactivity with all these MoAb. Numbers of LC were slightly reduced, but the reduction was not significant statistically. The presence of Birbeck granules in LC of op/op mice was confirmed by electron microscopy but the cytoplasmic projection of LC was not prominent. From these results, it appears obvious that the development and differentiation of LC do not require M-CSF. PMID- 1431209 TI - Stimulation of Langerhans cell migration by tumor necrosis factor alpha (TNF alpha). AB - Following topical exposure of mice to skin-sensitizing chemicals, Langerhans cells (LC), many of which bear antigen, are stimulated to migrate via the afferent lymphatics to draining lymph nodes. Consistent with the acquisition of potent immunostimulatory activity, LC while in transit to lymph nodes, are subject to a functional and phenotypic maturation thought to be mediated by granulocyte/macrophage colony-stimulating factor (GM-CSF) and possibly other epidermal cytokines. An interesting question is the nature of the stimulus that initiates the migration of LC from the epidermis. We have examined the influence of intradermal tumor necrosis factor alpha (TNF-alpha), another epidermal cytokine, on the accumulation of dendritic cells (DC) in draining lymph nodes. Murine, but not human, recombinant TNF-alpha caused a rapid and concentration dependent increase in the frequency of DC in draining nodes. The conclusion drawn is that local production of TNF-alpha provides one signal for LC migration during cutaneous immune and inflammatory responses. PMID- 1431211 TI - Polymorphism of the human genome: markers for genetic linkage analyses in heritable diseases of the skin. PMID- 1431210 TI - Migration of Langerhans cells from carcinogen-treated sheep skin. AB - To define the mechanism(s) of carcinogen depletion of Langerhans cells (LC) from skin, the migration of LC from the skin to the regional lymph node was examined in carcinogen-treated, antigen-treated, and control sheep. This was assessed by cannulation of afferent lymphatic vessels that drain the treated areas of skin or the efferent lymphatic draining the regional lymph node. Cells draining from test or control skin were continuously collected and enumerated by indirect immunofluorescence and flow cytometry using specific anti-CD1 monoclonal antibodies. There was a marked increase in the rate of LC migration in the 8 h following the application of the contact sensitizing antigen trinitrochlorobenzene (TNCB). The chemical carcinogen 7,12 dimethylbenz(a)anthracene (DMBA) triggered a tenfold-greater migration of LC compared with TNCB--with the peak response at 5 d. After DMBA treatment LC were also detected in the efferent lymph of the regional lymph node. It is concluded that the depletion of LC from carcinogen-treated skin is due to the increased LC migration and not carcinogen-induced cell death. PMID- 1431213 TI - Migration of Langerhans cells into the epidermis of human skin grafted into nude mice. AB - In a previous study, it was demonstrated that human Langerhans cells (LC) are preserved in human skin grafted onto a nude mouse. Moreover, although it was observed that mouse LC of the host invade skin grafts from allogeneic mouse or rat, they do not penetrate in human skin grafts. In most of the human skin equivalent systems produced in vitro, LC appear to be lost. The present study was designed to investigate whether the mouse LC will repopulate a human skin equivalent. For this purpose, two different systems of skin equivalent have been grafted into the nude mouse. They were composed of human keratinocytes deposited on dead human dermis, or on lattice composed of human fibroblasts embedded in type I collagen. At different times after grafting, the presence of LC in the transplants was assayed either by indirect immunofluorescence or by electron microscopy. Indirect immunofluorescence was performed on frozen sections or on epidermal sheets with anti-Ia, anti-HLA-DR, or OKT6 antibodies. It was observed that, at 2 months after grafting, Ia(+) HLA-DR(-) OKT6(-) cells are present in grafted human epidermis. Moreover, LC with typical Birbeck granules are also detected by electron microscopy. It could be concluded, from this study, that mouse LC can repopulate human epidermis devoid of human LC. PMID- 1431212 TI - Cytokine-stimulated human dermal microvascular endothelial cells produce interleukin 6--inhibition by hydrocortisone, dexamethasone, and calcitriol. AB - The effects of lipopolysaccharide (LPS), recombinant human tumor necrosis factor alpha (TNF), recombinant human interleukin 1-beta (IL-1 beta), and interferon gamma (IFN-gamma) on IL-6 production were determined by enzyme-linked immunosorbent assay (ELISA) and by Northern blot analysis in cultured human dermal microvascular endothelial cells (HDMEC). Unstimulated HDMEC did not produce significant amounts of IL-6, whereas lipopolysaccharide (LPS), TNF, and IL-1 beta were potent inducers of HDMEC-derived IL-6 production. Treatment with IFN-gamma had no effect. IL-1 beta stimulation resulted in pronounced IL-6 production after 4 h, followed by complete downregulation at the transcriptional level after 24 h. In contrast, LPS and TNF induced prolonged stimulation of IL-6 production by HDMEC as IL-6 mRNA transcripts were still detected after 24 h treatment and IL-6 protein was markedly increased at this timepoint. The effects of hydrocortisone, dexamethasone, calcitriol, acitretin, and cyclosporin A on TNF or IL-1 beta-induced IL-6 production by HDMEC were determined by ELISA. Both hydrocortisone and dexamethasone dose-dependently inhibited the cytokine-induced IL-6 production, whereas the inhibition by calcitriol was less pronounced. In contrast, acitretin and cyclosporine A had no influence on cytokine-induced HDMEC IL-6 production. These results disclose dermal endothelial cells as a major source for the pro-inflammatory cytokine IL-6, involved in the regulation of inflammatory skin processes. As IL-6 seems to play a key role in the pathogenesis of psoriasis, the beneficial effects of corticosteroids and calcitriol in this disease may partly be explained by their ability to inhibit HDMEC-derived IL-6 production. PMID- 1431214 TI - Mapping of the trichohyalin gene: co-localization with the profilaggrin, involucrin, and loricrin genes. AB - The chromosomal location of the gene encoding the human hair follicle protein trichohyalin has been determined by in situ hybridization. The human gene has been localized to the region 1q21.1-1q23 (probably 1q21.3) using a sheep trichohyalin cDNA probe. The genes encoding three other epithelial proteins, namely, profilaggrin, involucrin, and loricrin, are also located in the same region of chromosome 1, which, together with their similar gene and protein structures, suggests that the four proteins form a novel superfamily of epithelial structural proteins. PMID- 1431215 TI - Anchoring fibrils, collagen VII, and neutral metalloproteases in recessive dystrophic epidermolysis bullosa inversa. AB - Structure of the anchoring fibrils, expression of collagen VII, and gelatinolytic activity in skin fibroblasts were assessed in six patients with epidermolysis bullosa dystrophica (EBD) inversa and in control groups consisting of probands with other EBD subtypes and healthy individuals. All six patients with EBD inversa, as well as the patients with generalized non-mutilating and localized EBD, showed positive staining with antibodies to collagen VII, the major anchoring fibril protein. Four patients with severe generalized mutilating EBD exhibited negative staining. Ultrastructurally, normal anchoring fibrils were demonstrable in uninvolved skin of patients with localized, inversa, and generalized non-mutilating subtypes. At the same time, a high degree of variability was observed in the amount and quality of anchoring fibrils in the various stages of lesional skin, including co-existence of normal and partially degraded anchoring fibrils. Of all 12 patients only one localized and two inversa cases showed an increased gelatinolytic activity in vitro. However, the high activity was associated with neither the severity of the disease nor the inversa subtype. In addition, intact collagen VII could be extracted from the dermis of one inversa patient. The present data show no correlation between increased in vitro gelatinolytic activity and abnormalities of the anchoring fibrils or collagen VII in skin of patients with recessive EBD, and therefore suggest molecular heterogeneity of the causative pathogenetic mechanisms. PMID- 1431216 TI - Characterization of biologic properties of wound fluid collected during early stages of wound healing. AB - The clinical effects of occlusive dressings on wound healing are well documented. However, the underlying biologic mechanisms associated with moist healing are not well understood. Experimental studies and clinical experience have shown enhanced eschar and clot removal, re-epithelialization, and collagen synthesis under occlusion, suggesting the possibility of elevated activities of proteinases and other effectors, e.g., growth factors, in the moist wound environment. To gain an insight into the biology of early wounds under occlusion, we have carried out biologic and biochemical analyses on fluids from occluded full- and partial thickness wounds. Metalloproteinase activities were detected in the wound fluid samples. When applied to cultured dermal fibroblasts, mitogenic activity was observed with fluids from full-thickness wounds. Wound fluid-stimulated accumulation of urokinase-type plasminogen activator by fibroblasts was also observed in a time-dependent manner. Stimulation of metalloproteinase accumulation by fibroblasts was also observed. We have further demonstrated the presence of platelet-derived growth factor-like and basic fibroblast growth factor-like factors in wound fluid by antibody neutralization of their biologic activities. Proteinase presence and proteinase stimulatory activity of wound fluid retained in the occluded wound may contribute to an enhanced proteolytic environment in these wounds in comparison to non-occluded "dry" wounds. The presence of growth factors and the potential abilities of proteinases to activate latent growth factors and generate chemotactic peptides through connective tissue breakdown may also contribute to the enhanced healing of occluded wounds. PMID- 1431217 TI - A novel monoclonal antibody to a distinct subset of cutaneous dendritic cells. AB - A monoclonal antibody was generated by immunizing rats with Langerhans cell (LC) enriched epidermal cells obtained from BALB/c mouse earskin after epicutaneous application of the contact sensitizer 2,4-dinitrofluorobenzene (DNFB). The antibody 4F7 detects in normal mouse skin, few dermal cells showing the morphologic, phenotypic, and functional properties of accessory dendritic cells, but lacking Birbeck granules. The capacity to stimulate allogenic T cells in the mixed leucocyte reaction resembles that of freshly isolated LCs. After DNFB application, an increased number of 4F7+ dendritic cells are found in the dermis and, in addition, some labeled dendritic cells occur in the epidermis. Some of the latter cells exhibit cytoplasmic Birbeck granules. Remarkably, there is no increase of the 4F7+ cells in the regional lymph nodes after DNFB treatment. These data suggest that the 4F7 antibody labels distinct dendritic cells of the mouse skin that are involved in the mediation of contact sensitization and probably represent immature LCs. PMID- 1431218 TI - Protein kinase C in normal human epidermal keratinocytes during proliferation and calcium-induced differentiation. AB - Recent evidence has implicated protein kinase C (PKC) in the etiology of hyperproliferative diseases such as psoriasis and non-melanoma skin cancer. In this study, PKC activity, immunoreactive protein, and phorbol ester-binding kinetics were examined in primary cultures of normal human epidermal keratinocytes (NHEK) in order to elucidate the relationship between PKC and NHEK proliferation and differentiation. NHEK were maintained in a proliferative phase in serum-free low-calcium (0.15 mM) medium, and then were exposed to high calcium (1.6 mM) in order to stimulate growth arrest and differentiation. Staurosporine was inhibitory to Ca(++)-induced differentiation. Scatchard analysis of phorbol binding indicated that exposure to high calcium for 24 h increased the number of binding sites (Bmax) by fivefold. In correlation with the ligand-binding results, PKC activity was extremely low in proliferating (low-calcium) NHEK compared to differentiating cells (high calcium). When assayed after 24, 48, and 72 h, high calcium induced tenfold or greater increases in Ca++/phospholipid-dependent phosphotransferase activity. Immunoblot analysis of NHEK PKC using antibodies directed against the hinge region of PKC alpha/beta also indicated that exposure to high calcium resulted in higher levels of immunoreactive protein. Therefore, PKC in NHEK appears to be upregulated under conditions of Ca(++)-induced growth arrest and differentiation. In addition, NHEK and other human skin cell particulate fractions contain a protein of approximately 116 kDa that is highly immunoreactive to an antibody to PKC alpha/beta, which coelutes from DEAE sephacel under the same buffer conditions as the 80-kDa PKC. PMID- 1431219 TI - Scanning electron microscopy of the epidermal lamina densa in normal human skin. AB - The lamina densa of normal human epidermis was exposed by treatment with 1 M sodium chloride and was examined by high-power scanning electron microscopy before and after trypsinization. Localization of type IV collagen in the lamina densa was also studied by transmission and scanning immunoelectron microscopy. Before trypsinization, the surface of the lamina densa consisted of microridges and microvalleys. The microridges varied in height and were connected with each other. They were arranged in a concentric fashion around the tips of the dermal microprojections. At a higher magnification, the surface of the lamina densa was composed of densely packed cobblestone-like structures approximately 7-15 nm in size, between which were interspaces 4-11 nm wide. These structures expressed type IV collagen. After trypsinization, the lamina densa was found to be composed of microfilaments approximately 10 nm thick showing beaded appearances. These microfilaments exhibited the same cobblestone-like structures as the lamina densa surface. Observation of the torn lamina densa demonstrated anchoring fibrils and oxytalan fibers that were attached to the lamina densa itself. Another kind of filament about 7 nm thick linked the anchoring fibrils and the oxytalan fibers. Beneath the lamina densa was a network of fibers about 40-50 nm thick, which was composed of collagen fibers and possibly also elaunin fibers. In conclusion, this study revealed the detailed surface ultrastructure of the epidermal lamina densa and its underlying filamentous elements. PMID- 1431220 TI - Fibronectin gene transcription is enhanced in abnormal wound healing. AB - Abnormal wound healing in susceptible individuals can result in the formation of keloids that have an elevated content of extracellular matrix material compared to normal scars. Keloid-derived fibroblasts exhibit as much as a four-fold increase in the rate of fibronectin biosynthesis compared to fibroblasts from normal dermis and normal scars. Altered biosynthesis is due to an increase in the steady-state level of fibronectin mRNA, and in this investigation we have identified the level of fibronectin gene expression that is responsible for this increase. The rate of fibronectin gene transcription was found to be increased as much as threefold in keloid fibroblasts when compared to normal fibroblasts. Other possible changes that could account for the elevated level of fibronectin mRNA in keloids, such as increased copy number of the fibronectin gene or decreased turnover of fibronectin mRNA were also examined. The possibility of altered gene dosage was eliminated because chromosome content, G-banding patterns, and fibronectin gene content of keloid fibroblasts were all found to be normal. Analysis of fibronectin mRNA degradation revealed a half-life of approximately 13 h, and the residual fibronectin mRNA was observed to remain full length during this time period in both keloid and normal fibroblasts. Thus, altered degradation of fibronectin mRNA is unlikely to contribute to overproduction of fibronectin in keloids. Increased translational competence of fibronectin mRNA in keloids was also eliminated as a contributing factor because fibronectin mRNA remaining after one half-life were equally available for translation in both cell types. Although stimulation of transcription may not entirely account for the increase in fibronectin biosynthesis in keloids, this mechanism is best able to account for the majority of the change. PMID- 1431221 TI - Comparative epidermal Langerhans cell migration studies in epidermal and epidermal/dermal equivalent grafts. AB - Immigration of Langerhans cell precursors from the peripheral blood to the skin was studied in human grafts placed on severe combined immunodeficient (SCID) mice. Monocyte fractions of human blood were injected intraperitoneally to SCID bearing either reconstituted (Langerhans cell free) epidermal sheets (E) or living skin equivalents (E/D) consisting of both epidermis and dermis. A range of immunocytochemical and ultrastructural markers was employed to monitor the colonization of the grafts, i.e., CD1a/c, Birbeck granules. In situ hybridization with probes against Alu sequences of human DNA were employed together with immunostaining for MHC class I mouse and human antigens to document graft survival. Although unequivocal LC were detected within E grafts, including both human (CD1a positive) and murine (NLDC-145 positive), no migration was achieved in the E/D situations. PMID- 1431222 TI - Inhibition of cutaneous contact hypersensitivity in the mouse with systemic or topical spiperone: topical application of spiperone produces local immunosuppression without inducing systemic neuroleptic effects. AB - We tested the ability of the neuroleptic agent spiperone (8-[3-(p fluorobenzoyl)propyl]-1-phenyl-1,3,8-triazaspiro-[4.5] decan-4- one) to influence the tissue swelling and leukocyte infiltration associated with T-cell--dependent immune responses, i.e., contact hypersensitivity reactions, in mice. Contact hypersensitivity reactions were elicited by applying the haptens oxazolone or dinitrofluorobenzene topically to one or both ears 5-8 d after epicutaneous sensitization. When spiperone was given subcutaneously at a dose of 30 or 150 mg/kg, 1 h after challenge with oxazolone, cutaneous contact hypersensitivity to this hapten was significantly diminished. When applied topically in concentrations as low as 0.08% (w/w), preparations of spiperone significantly suppressed both the tissue swelling and the leukocyte infiltration associated with the elicitation phase of contact hypersensitivity. Topical treatment with spiperone also suppressed the sensitization phase of contact sensitivity. However, mice treated topically with spiperone, unlike those treated systemically, exhibited no drowsiness or other evidence of central nervous system effects. Spiperone expresses both serotonin and dopamine receptor antagonist activity. However, unlike spiperone, the chemically unrelated serotonin antagonists, trazadone and mianserin, and the dopamine receptor antagonist, haloperidol, were not effective in suppressing contact hypersensitivity. Our results indicate that spiperone can have immunosuppressive effects on contact hypersensitivity reactions in the mouse, even when applied topically in doses that lack neuroleptic effects, and that the mechanism of action of spiperone on the immune response may be independent of its serotonin or dopamine receptor blocking properties. PMID- 1431223 TI - Persistent immune tolerance to nickel and chromium by oral administration prior to cutaneous sensitization. AB - Oral administration of allergens, foreign proteins, or cell-bound antigens may induce systemic suppression of subsequent humoral and cell-mediated immune responses ("oral tolerance"). The induction of specific immune tolerance provides a potential strategy for treatment of T-cell-dependent immune diseases. Therefore, in depth studies into preconditions for optimal and persistent tolerance induction are mandatory. Here we report on such studies in a guinea pig model using the non-cross-reactive contact allergens nickel and chromium. Feeding per os of nickel sulfate or potassium dichromate did not trigger systemic TDTH effector functions. Instead, short feeding periods led to a dose-dependent, and metal-specific, suppression of subsequently induced allergic contact hypersensitivity. Administration of the allergens onto the oral mucosa was most effective in the induction of immune tolerance. When first sensitizing attempts were delayed until 1 year after feeding, the degree of unresponsiveness was reduced. In contrast, with cutaneous contacts starting shortly after the feeding period, tolerance was fully stable and undiminished for at least 2 years. Thus, in orally treated guinea pigs cutaneous contacts provide boosting tolerogenic signals, supporting the view that oral tolerance does not result from clonal deletion but from active antigen-specific immunosuppression. Indeed, unresponsiveness to cutaneous immunization could be transferred by lymphoid cells from fed guinea pigs in a metal-specific way. PMID- 1431224 TI - Composition of free long-chain (sphingoid) bases in stratum corneum of normal and pathologic human skin conditions. AB - The composition of molecular species of free long-chain bases (FLCB) isolated from stratum corneum of various human skin conditions was analyzed by the high performance liquid chromatographic and fast atom bombardment mass spectrometric methods. FLCB with carbon length ranging from 16 to 20 comprised about 0.3% of total lipids in stratum corneum of normal and pathologic skin conditions. Major FLCB included sphinganines and sphingenines with 18 to 20 carbons and some phytosphingosines such as t17:1, t18:1, t18:0, t20:1, and t20:0. Compared with stratum corneum of normal lower legs, molar percentages of FLCB having 18 carbons and those with 20 carbons were slightly higher and lower, respectively, in normal plantar epidermis, showing site-related differences in normal skin. Psoriatic scales and hyperkeratotic stratum corneum from clavus and plantar keratoderma contained increased levels of FLCB with 18 carbons and decreased levels of FLCB with 20 carbons. These findings may reflect abnormal keratinization in hyperkeratotic skin conditions. PMID- 1431225 TI - Proteoglycans synthesized by adult human epidermis in whole skin organ culture. AB - Adult human epidermis was cultured in whole skin organ culture under serum-free conditions in the presence of 35SO4. Proteoglycans (PG) comprised about 25% of the total (35SO4)-labeled material produced by epidermis. The rest of the incorporated activity displayed solubility characteristics typical of lipids. The molecular mass and the composition of the 35SO4-labeled epidermal PG and glycosaminoglycans (GAG) were studied using gel filtrations and agarose gel electrophoresis. The 35SO4-label of the epidermal PG was located in heparan sulfate (HS, approximately 75%) and chondroitin/dermatan sulfate (CS/DS, 25%), but not in keratan sulfate as determined by nitrous acid, chondroitinase AC II, chondroitinase ABC, and keratanase digestions, respectively. The molecular mass of the GAG chains was 10-40 kDa. The 35SO4-labeled PG were distributed between 60 and 600 kDa in agarose gel electrophoresis, with the highest activity at 350 kDa. Smaller activity peaks occurred at 150 and 60 kDa. Digestion of the PG with heparitinase removed most of the activity at 350 and 150 kDa, whereas chondroitinase ABC removed that at 60 kDa. A small amount of activity migrating between 600 and 1000 kDa was not affected by any of the GAG-degrading enzymes. Pulse chase experiments showed that the epidermal PG had an average half life of 24 h. The results thus demonstrate that human epidermis produces at least three different, rapidly metabolized PG. The PGs from 150 to 350 kDa contained heparan sulfate chains, whereas those at 60 kDa were chondroitin/dermatan sulfate PG. PMID- 1431226 TI - Presence of amelanotic melanocytes within the outer root sheath in senile white hair. AB - In order to determine whether amelanotic melanocytes are present in senile white hair, we attempted to detect tyrosinase mRNA and its protein using in situ hybridization and immunohistochemical staining. Specifically stained cells containing tyrosinase mRNA or its protein were detected by each technique in 7/23 (30.4%) or 4/14 (28.6%) senile white hairs, respectively. These cells were located in the outer root sheath between the hair-bulb and the infundibulum. Silver staining was used to determine whether melanin was present within the outer root sheath of the senile white hair. Because none of the 21 white hairs tested showed specific staining within the outer root sheath, the absence of melanin was confirmed. Thus our results suggest the presence of amelanotic melanocytes within the outer root sheath of senile white hair. PMID- 1431227 TI - Induction of the 72-kD heat shock protein in xeroderma pigmentosum complementation group A fibroblasts. AB - In mammalian cells, 72-kD heat shock protein (HSP72) is the major stress inducible protein that is thought to play a protective role against the various environmental stresses. In order to know the induction mechanism of HSP72, we examined the HSP72 in DNA repair-deficient xeroderma pigmentosum group A fibroblasts (XP2OSSV) and normal fibroblasts (WI38VA13) by the indirect immunofluorescence method using a monoclonal antibody specific for the inducible 72-kD protein. Heat-shock treatment of the same survival fraction (5% survival) induced HSP72 in xeroderma pigmentosum (XP) and normal cells. However, as compared with XP cells, normal cells showed the induction of HSP72 more rapidly and strongly. When XP and normal cells were irradiated with UVC at the same survival dose (10% survival), apparent induction of HSP72 was observed in both cell lines. In the case of UVC irradiation at the same dose (1.0 J/m2), though XP cells showed the induction of HSP72, HSP72 was not induced in normal cells. In both cell lines, heat-shock treatment caused more rapid induction of HSP72 than UV irradiation. These results suggest that the induction mechanism of HSP72 might be different between heat-shock treatment and UV irradiation. In addition, in the case of UV irradiation, the extent of DNA damage after DNA repair or the cell death might be involved in the induction of HSP72. PMID- 1431228 TI - Differential expression of calgranulin A and B in various epithelial cell lines and reconstructed epidermis. AB - The monoclonal antibody F12, raised against epidermal cells from a psoriatic lesion, decorated antigens highly expressed in psoriatic epidermis and in cultured normal human keratinocytes. In normal human skin, F12 reacted only with follicular keratinocytes. Characterization of the immunoprecipitated antigens by two-dimensional gel electrophoresis revealed their identity with calgranulin A and B. A semiquantitative study with various established epithelial cell lines demonstrated that the expression of calgranulin A and B in hyperproliferative keratinocytes correlates with their potential to undergo terminal differentiation. In epidermis reconstructed in vitro, the antigen expression was stimulated by retinoids and suppressed under vitamin A starvation. PMID- 1431229 TI - Quantitative determination of EGF-R during epidermal wound healing. AB - Little is known about the intrinsic regulation of growth factors of cytokines during the normal epidermal wound-healing processes in skin. A simplified model of wounding (tape stripping to remove the stratum corneum) was used to study the role of epidermal growth factor receptors (EGF-R) in this process. Although the dynamics of EGF-R in epidermal wound healing have not been determined, the immunoreactive EGF-R that are present presumably play an active role. Prior studies show that 1) EGF-R are present in increased numbers in proliferative skin diseases; 2) a hypertrophic epidermis, closely resembling normal wound healing, is induced in mouse skin by EGF injections; and 3) exogenous topical EGF potentiates wound healing. The number of immunoreactive receptors as measured by an enzyme-linked immunosorbent assay (ELISA) and histologic methods increased prior to an increase in epidermal thickness, total protein, and DNA content. This early increase in the levels of EGF-R was followed by a sharp decline in EGF-R and subsequent decline in epidermal thickness (hypertrophy), total protein, and DNA levels. Alterations in the temporal sequence in these parameters indicate that the EGF-R-mediated signaling systems play an active role in epidermal wound repair. PMID- 1431231 TI - Keratinocyte migration is partially supported by the cell-binding domain of fibronectin and is RGDS-dependent. AB - Fibronectin (FN) plays a key role in cell attachment, embryonic development, and wound healing. In this respect, it is known that FN promotes keratinocyte migration. The aim of this study was to examine specific FN domains (120-kD cell binding fragment, 45-kD collagen fragment, and 40-kD heparin fragment) and a biologically active peptide within the molecule (RGDS) for their ability to influence human keratinocyte (HK) locomotion. HKs were plated on gold salts coated with different substrates (type IV collagen, FN with or without the RGDS peptide, and the three FN fragments). After 20 h, locomotion tracks were quantified by computer-assisted image analysis that determines the area of each microscopic field occupied by migration tracks, a so-called migration index (MI). MIs on type IV collagen and FN were 39.14 +/- 2.8% and 30 +/- 0.4%, respectively. The maximal MIs on the collagen-binding domain and heparin-binding domain of FN were similar to our negative controls (plastic and albumin): 3 +/- 1%. In contrast, the maximal MI on the cell-binding fragment of FN was 18.45 +/- 2.1%. The effect of the cell-binding domain on keratinocyte motility was found to be dose dependent. Moreover, we could specifically inhibit the FN-driven locomotion using the RGDS sequence contained in the cell-binding fragment. We did not observe a synergistic effect (i.e., a higher MI) when we added the three fragments in a same dish. These results suggest i) that the cell-binding fragment of FN partially supports HK locomotion, ii) that other untested FN domain(s) should act in synergy with the cell-binding fragment to promote keratinocyte locomotion, or alternatively iii) that the FN function of promoting cell migration resides within the FN cell-binding domain, but the proper presentation of this domain to the cell requires an intact, native FN molecule, and iv) that the RGDS sequence is essential for HK movement. PMID- 1431230 TI - Keloid fibroblasts exhibit an altered response to TGF-beta. AB - Treatment with transforming growth factor beta 1 (TGF-beta 1) results in stimulation of total protein synthesis in normal dermal fibroblasts but not in keloid fibroblasts, suggesting that the TGF-beta regulatory program is altered in keloid fibroblasts. However, both keloid and normal fibroblasts treated with TGF beta 1 exhibit accelerated fibronectin biosynthesis, indicating that keloid cells can respond to TGF-beta 1. In the absence of serum, the TGF-beta 1-induced increase in fibronectin biosynthesis occurs more rapidly in keloid fibroblasts, also suggesting modification of this regulatory pathway. The TGF-beta 1-mediated increase in keloid fibronectin production is independent of the steroid regulatory pathway for fibronectin, which accelerates synthesis by means of a post-transcriptional mechanism. Thus, TGF-beta 1 stimulation of fibronectin production in keloid cells is likely to involve a transcriptional mechanism and keloid overproduction of extracellular matrix components may be due to an inherent modification of the TGF-beta regulatory program. PMID- 1431232 TI - Effects of immunomodulatory cytokines on the presentation of tumor-associated antigens by epidermal Langerhans cells. AB - The recognition and presentation of tumor-associated antigens by cutaneous antigen-presenting cells (APC) may play an important role in the establishment of effective defense mechanisms against newly emerging tumors in the skin. Recent data demonstrate the ability of I-A+ epidermal cells (Langerhans cells) to present tumor-associated antigens for the induction of protective tumor immunity and elicitation of delayed-type hypersensitivity against the murine spindle cell tumor, S1509a. Furthermore, the local cytokine microenvironment in the vicinity of a cutaneous neoplasm may regulate the ability of resident epidermal APC to initiate and/or to elicit protective immunity against incipient cutaneous neoplasms. This article summarizes the effects of granulocyte-macrophage/colony stimulating factor (GM-CSF), interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF alpha), transforming growth factor-beta (TGF beta), and interferon-gamma (IFN gamma) on the modulation of antigen presentation by epidermal APC. Our data indicate that these cytokines significantly and differentially modify the ability of epidermal cells to present tumor-associated antigens and that their effects differ with regard to induction of primary immunity (sensitization) or elicitation of secondary immune responses. PMID- 1431233 TI - Workshop on pseudoxanthoma elasticum: molecular biology and pathology of the elastic fibers. Jefferson Medical College, Philadelphia, Pennsylvania, June 10, 1992. PMID- 1431234 TI - Industry-funded dermatologic research within academia in the United States: fiscal and ethical considerations. PMID- 1431235 TI - Keratinocytes in vitiligo. PMID- 1431237 TI - Multiple endocytic pathways. PMID- 1431236 TI - Deleterious effects of cis-urocanic acid and UVB radiation on Langerhans cells and on induction of contact hypersensitivity are mediated by tumor necrosis factor-alpha. AB - Ultraviolet B (UVB) light disrupts epidermal Langerhans cells (LC) universally and impairs the induction of contact hypersensitivity (CH) to epicutaneously applied haptens in certain strains of mice. Similar effects are observed when tumor necrosis factor-alpha (TNF alpha) is injected intradermally (ID) in mice. Trans-urocanic acid (UCA), a photoreceptor for UVB radiation, is known to be immunosuppressive. To determine whether cis-UCA is important in the process by which UVB and/or TNF alpha act in the skin, cis-UCA was injected ID into C57BL/6, C3H/HeN, BALB/c, and C3H/HeJ mice. Whole mounts of epidermis were removed 5 h later and stained immunochemically with anti-Ia antibodies. Microscopy revealed that Ia-bearing LC had lost their dendrites, had rounded up, and were reduced in number in all strains examined. Moreover, when dinitrofluorobenzene (DNFB) was applied epicutaneously to the injected site, induction of CH was grossly impaired. When neutralizing anti-TNF alpha antibodies were administered intraperitoneally 2 h prior to ID injection of cis-UCA, the deleterious effects on LC and CH induction were largely reversed. These results indicate that the actions of cis-UCA on LC and on CH induction are very similar to those achieved by ID injections of TNF alpha and by cutaneous exposure to low-dose UVB. Because the effects of UVB radiation and cis-UCA are reversed by anti-TNF alpha antibodies, we propose that UVB radiation impairs the induction of CH in mice by converting trans-UCA to cis-UCA within the epidermis; cis-UCA in turn causes the local release of TNF alpha, which thwarts sensitization by its ability to alter the functional program of epidermal Langerhans cells, thereby preventing the induction of CH. PMID- 1431238 TI - IL-3 production as an in vitro marker of the genetically determined traits of UVB susceptibility and UVB resistance. AB - The capacity of low-dose ultraviolet B (UVB) radiation to disrupt epidermal Langerhans cell function and to prevent the induction of contact hypersensitivity (CH) is genetically determined in mice and men. In mice, Tnf alpha and Lps are the genetic loci at which reside alleles that dictate susceptibility and resistance to the deleterious effect of UVB radiation. Detection of the UVB susceptibility (UVB-S) and UVB-resistance (UVB-R) traits relies upon the in vivo end point of contact hypersensitivity, and is cumbersome, labor intensive, and time consuming. It has recently been reported that hapten-immune murine T cells can secrete interleukin-3 (IL-3) in vitro when exposed to hapten-derivatized syngeneic stimulator cells. To determine whether this assay might be useful in distinguishing UVB-R from UVB-S mice, panels of UVB-susceptible (C57BL/10, C3H/HeN) and UVB-resistant (A/J, BALB/c, C3H/HeJ) mice were sensitized epicutaneously with dinitrofluorobenzene (DNFB). When challenged in vitro 6 d later with dinitrophenyl-derivatized stimulator cells, T cells from all strains proliferated and secreted IL-3. Moreover, T cells from UVB-R mice that were sensitized through UVB-treated skin also made copious amounts of IL-3. However, T cells from UVB-S mice whose abdominal skin had been UVB irradiated prior to epicutaneous application of DNFB failed to secrete IL-3 in vitro, although the cells did proliferate. We conclude that following application of a sensitizing dose of hapten to UVB-exposed skin of UVB-S mice a) hapten-specific T cells are selectively unable to secrete IL-3 in vitro in response to hapten stimulation, and b) this inability is a reliable marker of the UVB-S trait. The IL-3 assay may prove useful in elucidating the mechanism by which UVB-exposed Langerhans cells activate regulatory T cells, and in detecting the UVB-S and UVB-R traits in humans. PMID- 1431239 TI - Effects of the immunosuppressive dipeptide L-leucyl-L-leucine O-methyl ester on epidermal Langerhans cells. AB - Pretreatment of newborn human foreskin epidermal cells (EC) with L-leucyl-L leucine methyl ester (Leu-Leu-OME) was found to dramatically inhibit their ability to serve as alloantigen-presenting cells in a primary, one-way, allogeneic mixed epidermal cell-lymphocyte reaction (MECLR) without significantly affecting EC viability. The Leu-Leu-OME-induced MECLR inhibition could not be accounted for by a cytotoxic effect on epidermal Langerhans cells (LC), the class II major histocompatibility (MHC) antigen-bearing EC type that is fully responsible for alloantigen presentation in a primary allogeneic MECLR. Pretreatment with Leu-Leu-OME was found to inhibit the culture-induced increase in surface expression of HLA-DR molecules on LC. These findings suggest that in addition to its cytotoxic effect on cells containing high levels of dipeptidyl peptidase I, Leu-Leu-OME can also perturb alloantigen-presenting cells that are not killed by this agent by modulating HLA-D region antigen expression, perhaps through its capacity to neutralize acid compartments within cells. In addition, these studies support the notion that the culture-induced upregulation of class II MHC antigens on epidermal LC is functionally associated with the enhanced alloantigen-presenting capabilities that these cells display after short-term culture and suggest that newly synthesized class II antigens might be critical to the alloantigen-presenting cell capabilities of LC. PMID- 1431240 TI - Accessory function of human Langerhans cells in the primary allogeneic T-cell response. AB - Beyond antigen processing and presentation, antigen-presenting cells must convey additional signals that are necessary for T-cell activation and proliferation. In this study we analyzed the accessory function of human Langerhans cells (LC) in the primary T-cell response to alloantigens. We used paraformaldehyde-fixed LC suspensions to dissociate membrane-associated accessory structures from soluble activating factors. When freshly prepared LC-enriched (eLC, 8-20% LC) epidermal cell suspensions were fixed, normal allogeneic T cells failed to proliferate. This defect cannot be overcome by the addition of either interleukin (IL)-1 and/or IL-6 during the mixed skin cell lymphocyte reaction (MSLR). By contrast, when eLC were first incubated for 3 d, and especially in the presence of interferon gamma (IFN-gamma) before fixation, they retained significant allostimulatory property that did not correlate with increased MHC class II antigen expression. Furthermore, we showed that once LC have been activated, IL 1, but not IL-6, could serve as a co-stimulatory factor in the primary allogeneic T-cell response. In conclusion, the data suggest that human LC accessory function is not constitutive but requires an activation step, which can be provided by IFN gamma during LC-T-cell interaction. PMID- 1431241 TI - Infection of accessory dendritic cells by human immunodeficiency virus type 1. AB - Many details of the pathogenesis of the human immunodeficiency virus type 1 remain to be elucidated. Details of how the virus gains entry via the mucosal surface upon sexual contact or during breast feeding remain obscure. The means by which the infection travels throughout the body as well as the nature of the major reservoirs of virus infection remains, for the most part, unknown. Recent studies raise the possibility that cells of the Langerhans/dendritic lineage play a central role in human immunodeficiency virus (HIV-1) infection and pathogenesis. It has been known for several years that veiled dendritic cells in the circulation as well as skin Langerhans are infected in people with prolonged HIV-1 infections. More recently it has been found that a large burden of viral DNA sequences is found, not only in the circulating T-cell population, but also in a population that is defined as a non-T, non-B, non-monocyte/macrophage population rich in T-helper dendritic cells. Detailed analysis of infection of primary blood-derived T-helper dendritic cells by HIV-1 shows that such cells are the most susceptible cells in the blood to infection by this virus. The cells also produce much more virus per cell than do purified populations of other blood mononuclear cells. Moreover, primary blood-derived T-helper dendritic cells are not killed by infection by HIV-1. These cells are susceptible to lymphotropic, monocyte tropic, and primary isolates of HIV-1. The sensitivity of primary blood derived T-helper dendritic cells to infection by HIV-1 has been shown to be attributable to rapid uptake of virus particles as well as rapid synthesis of viral DNA. Subsequent steps of virus replication also occur more rapidly and more efficiently in populations of primary blood-derived T-helper dendritic cells than they do in purified preparations of blood-derived T cells and monocyte/macrophages. Studies with primates using the simian immunodeficiency virus (SIV) show that dendritic cells at the surface of sexual mucosa are rapidly infected upon exposure to high concentrations of the virus. SIV is also produced in abundance in Langerhans cells located at the surface of the sexual mucosa in animals infected for prolonged periods of time. PMID- 1431242 TI - In vitro HIV-1 entry and replication in Langerhans cells may clarify the HIV-1 genome detection by PCR in epidermis of seropositive patients. AB - Being dendritic antigen-presenting cells in skin and mucous membrane, Langerhans cells (LC) occur in areas at risk for inoculation by human immunodeficiency virus (HIV), and the question whether LC act as a target, reservoir, or vector for transmission of HIV has given rise to much controversy. To address this question, we first analyzed the epidermal compartment of skin from patients seropositive for HIV DNA. Second, we tested the susceptibility of each cell type normally found in this compartment to in vitro infection by HIV-1. A non-denatured DNA was obtained from epidermal sheets after a thermochemical treatment of biopsies (0.5 M ethylenediaminetetraacetic acid (EDTA), pH 7.5 at 60 degrees C for 90 seconds). Optimization of amplification of viral genome was performed with three primer pairs derived from gag, env, and pol sequences. Polymerase chain reaction (PCR) products were analyzed by Southern blot. Viral genome was found in five of 11 HIV seropositive patients. To control the permissivity of epidermal cell population for HIV, cells isolated from the epidermal sheet of normal skin by trypsinization were co-cultured with HIV-1-carrying promonocytic cells (U937) and observed by electron microscopy. After 3-6 h of co-culture, numerous virions were either tightly bound or apparently engaged in the process of internalization through receptor-mediated endocytosis. At day 4 of co-culture, some infected LC appeared to release mature viral particles through bud formation. The in vitro HIV-1 entry and replication in LC may confirm the presence of the HIV-1 genome by PCR in epidermis of seropositive patients. The consequences of the permissivity of LC for HIV on the antigen-presenting function remain to be determined. PMID- 1431243 TI - Regulation of complement activity by vaccinia virus complement-control protein. AB - A major protein secreted by vaccinia virus-infected cells has structural similarity to the super-family of complement-control proteins. This vaccinia complement-control protein (VCP) was studied to determine how it regulates complement activation. VCP was bound by C4b and C3b and served as a cofactor with factor I in cleaving these two molecules. VCP inhibited the formation and accelerated the decay of the classical C3 convertase. It also accelerated decay of the alternative pathway convertase, although higher concentrations were apparently needed. In vitro, therefore, VCP interfered with the classical and alternative complement pathways at several steps. In vivo, this interference may increase the virulence of vaccinia virus by enabling it to escape attack by the host's complement system. PMID- 1431244 TI - Differential antibody responses to rubella virus infection in males and females. AB - Specificities of human rubella virus (RV)-specific IgG, IgM, and IgA antibodies for RV structural proteins (envelope E1 and E2 and capsid) and an E1 domain represented by a synthetic peptide (BCH-178) were determined by immunoblot and ELISA techniques in sera from rubella-infected individuals. Sequential sera were obtained from 67 females and 32 males during acute and convalescent infection phases. Males and females had differences in all antibody classes, especially during the early acute infection phase. At no time during follow-up were IgA anti E2 antibodies detected in males, in contrast to the case in females. Significantly lower levels of IgG antibody directed to E2 were also observed in males. Males had earlier onset of E1-specific IgG and IgM antibodies with a greater proportion of total RV antibody response directed to E1 (IgG) or E1 peptide (IgM). These differences suggest there are hormonal and genetic influences on immune recognition of RV proteins that may be related to the increased incidence of rubella-associated arthropathy in females. PMID- 1431245 TI - The role of double-stranded RNA in induction of the acute-phase response in an abortive influenza virus infection model. AB - The inducer of the acute-phase response in "flu-like" viral infections is not defined. The hypothesis that virus-associated double-stranded (ds) RNA serves this function was investigated by comparison of several acute-phase responses (fever and sleep patterns, white and nucleated red blood cell levels, serum antiviral activity and ceruloplasmin) induced by the synthetic dsRNA polyriboinosinic:polyribocytidylic acid (poly[rI:rC]) with those induced by influenza virus in rabbits. The capacity of either dsRNA or influenza virus to induce hyporesponsiveness with respect to these acute-phase parameters upon rechallenge with the same agent or cross-challenge 24 h later was also examined. Poly(rI:rC) induced only minimal hyporesponsiveness to itself but was a potent inducer of hyporesponsiveness to virus with respect to fever, sleep, leukograms, and antiviral activity. Therefore, poly(rI:rC) can substitute for virus in terms of induction of acute-phase hyporesponsiveness, suggesting that dsRNA of viral origin triggers the acute-phase response in this model of influenza. PMID- 1431246 TI - Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975-1988. AB - Cases of adult botulism (n = 309) were studied to identify clinical differences between toxin types and to evaluate the sensitivity of diagnostic laboratory testing. Patients with illness from type E toxin had the shortest incubation periods. Sporadic case-patients were more severely ill: 85% required intubation compared with only 42% in multiperson outbreaks. Of patients with type A botulism, 67% required intubation compared with 52% with type B and 39% with type E. Toxin testing was positive for 40%-44% of serum and stool specimens obtained within 3 days of toxin ingestion and for 15%-23% of specimens obtained thereafter, while 37% of stool specimens obtained > 3 days after toxin ingestion were positive by culture. Patients with type A botulism have more severe illness. In general, specimens obtained early are more likely to be positive by toxin assay, and stool cultures are more sensitive than toxin detection for specimens obtained later in the illness. PMID- 1431247 TI - Systemic and mucosal antibody responses to toxin A in patients infected with Clostridium difficile. AB - The systemic and mucosal humoral response to toxin A, the primary virulence factor of Clostridium difficile, was measured in sera and intestinal secretions from 21 patients with C. difficile diarrhea, 9 asymptomatic C. difficile fecal excretors, and 10 noncolonized control subjects. Toxin A-specific IgG was higher in convalescent sera of the patients with diarrhea (mean +/- SE, 990 +/- 260 ng/mL) than in acute sera (620 +/- 150 ng/mL), in sera from asymptomatic excretors (410 +/- 140 ng/mL), or control subjects (320 +/- 50 ng/mL; P < .05 convalescent vs. control). The pattern of toxin A-specific serum IgA and intestinal secretory IgA levels was similar to that of serum IgG in these groups. Neutralization of toxin A was demonstrated in 5 of 14 convalescent sera but only 1 of 13 acute sera (P = .04). However, the presence of neutralizing activity was independent of the subsequent clinical response. Therefore, most patients convalescent from C. difficile diarrhea demonstrate systemic and mucosal antibodies to toxin A, but these antibodies following natural infection do not appear to alter the clinical course of C. difficile infection. PMID- 1431248 TI - Growth of Escherichia coli in human urine: role of salt tolerance and accumulation of glycine betaine. AB - Glycine betaine is a powerful osmoprotectant molecule present in the inner medulla of the kidney and excreted into urine. It may be responsible for the ability of Escherichia coli to grow in hypertonic urine. Also, strains of E. coli that cause urinary tract infections may be more salt-tolerant than strains from other sites. To explore these questions, 301 isolates from blood, urine, or stool and 12 representative enteric strains were examined. Tolerance varied from 0.1 to 0.7 M NaCl (median, 0.5) in minimal medium. There were no significant differences in salt tolerance by site of isolation. A salt-sensitive enteric strain that responded poorly to glycine betaine and mutant strains lacking the ability to synthesize or transport glycine betaine did not grow well in hypertonic urine. Accumulation of glycine betaine appears to be a mechanism by which E. coli can adapt to external osmotic forces and grow in hypertonic urine. PMID- 1431249 TI - Antibodies against IgA1 protease are stimulated both by clinical disease and asymptomatic carriage of serogroup A Neisseria meningitidis. AB - IgA1 protease was purified from a strain of serogroup A Neisseria meningitidis subgroup IV-1, representative of bacteria that caused an epidemic of meningococcal meningitis in The Gambia in 1982-1983. ELISAs and immunoblot assays were done using this protease as antigen with paired acute- and convalescent phase sera from patients from that epidemic and from one in Finland caused by other serogroup A meningococci. Paired sera were also tested from healthy Gambians who were persistent nasopharyngeal carriers, persistent noncarriers, or persons who became carriers after the first serum sample was taken. The results correlated well between the two methods: Antibodies were stimulated by disease or acquisition of carriage, and they remained at a constant level upon continued carriage. PMID- 1431250 TI - Characterization of the serum antibody response to the capsular polysaccharide of Haemophilus influenzae type b in children with invasive infections. AB - The serum antibody response to the capsular polysaccharide of Haemophilus influenzae type b (Hib) was studied in 30 children aged 1 day-5 years with invasive Hib infections. From each child, serum was obtained 0-2 days, 5-11 days, 1 month, and 6-12 months after onset of symptoms. Total antibodies were determined with RIA and isotypes with ELISA. Only 2 children had antibody levels above the estimated protective level (0.15 microgram/mL) in the first serum sample. The antibody response was age dependent with wide individual variations. Children > or = 2 years had increases in IgG, IgM, and IgA antibodies with predominance of IgG. The initial IgG response was IgG1 and IgG2 with predominance of IgG1. In the last serum sample, IgG1 antibodies had decreased while IgG2 antibodies remained unchanged. Only 2 of 7 children < 1 year had a detectable antibody response. The correlation coefficient for total antibodies compared with the sum of IgG, IgM, and IgA was .88 (P < .0001) and for IgG compared with the sum of IgG1 and IgG2 was .97 (P < .0001). PMID- 1431251 TI - Changes in the distribution of Haemophilus influenzae type b clones associated with widespread infant vaccination in Finland. AB - Isolates from 646 consecutive Finnish Haemophilus influenzae type b (Hib) patients with systemic disease, collected before and during large-scale vaccinations with Hib conjugate vaccines, were analyzed by major outer membrane protein (OMP) subtyping, lipopolysaccharide (LPS) serotyping, and biotyping (BT). Strains with OMP-BT-LPS combinations (clones) 1-I-1 and 1c-I-1 disappeared at the same rate as the disease they were associated with. A preferential decrease in the number of isolates of clone 1-II-1 was recorded, whereas the reduction in disease caused by strains of clone 1-II-9 occurred at a lower rate than expected. The latter clone occurred mainly in the most densely populated area of Finland. Strains belonging to all the common Hib clones were isolated from the 16 infants who acquired Hib disease despite being (partially) vaccinated. Thus, Hib clones disappeared during mass vaccination with conjugate vaccines, although at different rates. PMID- 1431252 TI - The spread of multiply resistant Streptococcus pneumoniae at a day care center in Ohio. AB - Streptococcus pneumoniae, type 23F, resistant to penicillin (MIC, 2 micrograms/mL) and multiple other antimicrobic agents, was isolated from middle ear fluid of a child with otitis media attending a day care center in Ohio. To determine the extent of spread of this strain, nasopharyngeal culture surveys were done, and 52 carriers were identified among 250 children attending the index day care center. No carriers were found among 121 children at two other day care centers in the same urban area. Use of prophylactic doses of antibiotics (P < .001) and frequent use of antibiotics (P < 0.001) were risk factors for nasopharyngeal carriage. Carriers were more likely to have had frequent otitis media episodes (P < .02) and otitis media not responsive to antimicrobial therapy (P < .001). Strategies to limit the spread of highly resistant pneumococcal strains should include encouraging judicious use of antimicrobic agents and reevaluating indications for prophylactic use of antimicrobic agents. PMID- 1431253 TI - Recombinant murine interferon-gamma reversibly activates rat alveolar macrophages to kill Legionella pneumophila. AB - The interaction of interferon (IFN)-gamma, rat alveolar macrophages, and Legionella pneumophila was studied in vitro to define the effector cell potential of alveolar macrophages against an intracellular pathogen in a model in which the efficacy of IFN-gamma could be tested in vivo. Alveolar macrophages preincubated with IFN-gamma up-regulated Ia antigen and killed 0.5-4 logs of L. pneumophila over 4 days compared with 1-2 logs of bacterial growth in untreated cells. The bactericidal effect was dose dependent, evident over a wide range of bacterial inocula, and not suppressed by hydrocortisone. Preincubation with IFN-gamma was unnecessary and insufficient, as intracellular replication was reversed by exposure to IFN-gamma up to 48 h after infection, and neutralization of IFN-gamma after infection permitted bacterial growth. IFN-gamma thus converts alveolar macrophages from target cells to effector cells in host defense against L. pneumophila and may be of therapeutic benefit in legionellosis. PMID- 1431254 TI - Risk assessment and laboratory diagnosis of trichomoniasis in men. AB - Control of Trichomonas vaginalis is assuming higher priority because recent studies have suggested that trichomoniasis enhances susceptibility to human immunodeficiency virus infection and the risk for delivery of low-birth weight infants. In a cross-sectional study, 50 cases were identified among 447 men attending a sexually transmitted disease clinic. As previously reported, trichomoniasis was associated with nonchlamydial nongonococcal urethritis. Other risk factors included sexual contact with an infected woman or prior treatment for trichomoniasis or nongonococcal urethritis. Urethral and first-void urine cultures were positive in 80% and 68% of positive cases, respectively. When combined, these two cultures diagnosed 49 (98%) of 50 cases. These data suggest that criteria for selection of men for culture should include presence of nonchlamydial nongonococcal urethritis, recent exposure to trichomoniasis, or a history of trichomoniasis or nongonococcal urethritis. In addition, combining urethral and urine sediment cultures may prove accurate for evaluating T. vaginalis infection. PMID- 1431255 TI - Effectiveness of a human monoclonal anti-endotoxin antibody (HA-1A) in gram negative sepsis: relationship to endotoxin and cytokine levels. AB - Gram-negative sepsis is caused by endotoxin-induced release of tumor necrosis factor (TNF) and other cytokines. HA-1A is a human monoclonal antibody that binds specifically to endotoxin. HA-1A should prevent death in endotoxemic patients and reduce serum levels of TNF and interleukin-6 (IL-6). This hypothesis was tested in 82 septic patients who were randomly allocated to receive a single intravenous 100-mg dose of HA-1A or placebo. Pretreatment endotoxemia was detected in 27 patients (33%). Death occurred within 28 days of treatment in 8 (73%) of 11 placebo recipients and in 5 (31%) of 16 HA-1A recipients (P = .02). The median decrease in serum TNF level 24 h after treatment was 12 ng/L in patients given HA 1A and 0 ng/L in placebo recipients (n = 65; P = .04). For IL-6, this was 204 ng/L in patients given HA-1A and 44 ng/L in placebo recipients (n = 67; P = .4). Thus, HA-1A reduces mortality in septic patients with endotoxemia and lowers serum TNF levels. PMID- 1431256 TI - Factors associated with invasive lung aspergillosis and the significance of positive Aspergillus culture after liver transplantation. AB - From January 1981 to December 1990, 2180 patients underwent orthotopic liver transplantation at the University of Pittsburgh. Thirty-two patients (1.5%) were identified with invasive aspergillosis (29 lung, 2 intraabdominal, 1 meningitis). Of 29 patients with invasive lung disease, only 23 (79%) had positive culture (Aspergillus fumigatus, 20; Aspergillus flavus, 3). Forty-eight variables were analyzed and compared in 23 patients with invasive disease with positive cultures and 9 patients with colonization only. The variables associated with pulmonary invasive disease, by univariate analysis, were surgical time (P = .03), presence of laparotomies (P = .02), higher creatinine level at time of Aspergillus isolation (P = .01), and use of OKT3 (P = .02). However, in a multivariate analysis, only the last two (creatinine, OKT3) were associated with invasive lung aspergillosis. Of 4 patients with positive abdominal wound culture, 2 had local invasive aspergillosis. Therefore, positive cultures of Aspergillus organisms from respiratory secretions and wound drainage may represent invasive disease and should not be ignored. PMID- 1431257 TI - High-dose mefloquine in the treatment of multidrug-resistant falciparum malaria. AB - The therapeutic efficacy and toxicity of a high-dose (25 mg/kg) mefloquine regimen (M25) and the currently recommended regimen of 15 mg/kg (M15) were compared in 199 patients with acute falciparum malaria in an area with deteriorating multidrug resistance on the Thai-Burmese border. The clinical and parasitologic responses were significantly more rapid with M25. The incidence of treatment failures by day 7-9 was 7% for M15 and 1% for M25 (P = .03) and had increased to 40% and 9%, respectively, by day 28 (P < .0001). Overall failure rates were highest in children (P = .02). Parasite clearance times were a good predictor of the therapeutic response; all patients with parasitemia persisting > 5 days after treatment experienced subsequent recrudescence. Side effects were dose-related and included dizziness, anorexia, nausea, vomiting, and fatigue. Although vomiting < 1 h after treatment was more likely in young children, children overall tolerated mefloquine better than adults, and men better than women. The optimum treatment dose of mefloquine in this area is 25 mg/kg. PMID- 1431258 TI - Immunotherapy of respiratory syncytial virus infection in cotton rats (Sigmodon fulviventer) using IgG in a small-particle aerosol. AB - To determine whether aerosolized IgG can be used effectively in the treatment of respiratory syncytial virus (RSV) infections, cotton rats were infected intranasally with RSV and treated 3 days later with human IgG containing anti-RSV antibodies delivered in a small-particle aerosol. Pulmonary histology and virus titers were determined 24 h after IgG treatment. A single 15-min exposure to aerosolized IgG did not exacerbate pulmonary pathology and effected a 50-fold reduction in pulmonary virus titer (2.95 vs. 4.67 log10 geometric mean pfu/g for untreated controls, P < .001), which was comparable to that effected by intranasally instilled IgG (50 mg/kg) (3.24 vs. 4.67 log10 geometric mean pfu/g for controls, P < .001). A 15-min exposure to aerosolized ribavirin (20 mg/mL) was not effective in reducing pulmonary virus. This study suggests that aerosolized IgG could be useful in the treatment of RSV lower respiratory tract infections and that it compares favorably with ribavirin. PMID- 1431259 TI - Cholera in Piura, Peru: a modern urban epidemic. AB - In late January 1991, epidemic cholera appeared in Peru. Within 2 months, 7922 cases and 17 deaths occurred in Piura, a Peruvian city of 361,868. A hospital based culture survey showed that 79%-86% of diarrhea cases were cholera. High vibriocidal antibody titers were detected in 34% of the asymptomatic population. A study of 50 case-patients and 100 matched controls demonstrated that cholera was associated with drinking unboiled water (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.7-8.9), drinking beverages from street vendors (OR, 14.6; CI, 4.2-51.2), and eating food from street vendors (OR, 24.0; CI, 3.0-191). In a second study, patients were more likely than controls to consume beverages with ice (OR, 4.0; CI, 1.1-18.3). Ice was produced from municipal water. Municipal water samples revealed no or insufficient chlorination, and fecal coliform bacteria were detected in samples from 6 of 10 wells tested. With epidemic cholera spreading throughout Latin America, these findings emphasize the importance of safe municipal drinking water. PMID- 1431260 TI - Outbreak of cholera associated with crab brought from an area with epidemic disease. AB - From 31 March through 3 April 1991, 8 New Jersey residents developed severe, watery diarrhea after eating crabmeat brought back in the suitcase of a traveler to Ecuador. Stool cultures yielded toxigenic Vibrio cholerae O1, serotype Inaba, biotype El Tor from 4 persons, and vibriocidal antibody titers were > or = 1:640 in 7 persons, indicating recent infection with Vibrio cholerae O1. Eating crab was statistically associated with illness (P = .006); however, no leftover crabmeat was available for testing. All 8 patients fully recovered and no cases of secondary transmission were reported. This was the first reported incident of cholera in the continental United States associated with food transported from an area with epidemic disease. Discouraging the transport of perishable souvenir seafood may prevent further outbreaks. PMID- 1431261 TI - Controlled study of a new five-component acellular pertussis vaccine in adults and young children. AB - A new five-component acellular pertussis (AP) vaccine containing 10 micrograms of pertussis toxoid, 5 micrograms of filamentous hemagglutinin, 5 micrograms of combined agglutinogens 2 and 3, and 3 micrograms of pertactin was evaluated in adults and young children. AP vaccine was compared with saline placebo in 31 adults, and AP vaccine combined with diphtheria and tetanus toxoids (ADTP) was compared with whole cell DTP in 41 children, ages 16-20 months, who had received whole cell DTP during infancy. AP was mildly to moderately reactogenic in adults, with pain noted within 72 h and 5-8 days after immunization. ADTP was less reactogenic than DTP in children, with significantly decreased pain, redness, irritability, and fever and less use of acetaminophen reported. No late reactions were observed in any child. The multicomponent ADTP was immunogenic, with four fold or greater antibody rises to at least four pertussis antibody assays in all 15 immunized adults. Pertussis-specific antibody responses in children who received ADTP and DTP were similar. The multicomponent ADTP vaccine is currently being studied in a National Institute of Allergy and Infectious Diseases sponsored efficacy study in Sweden. PMID- 1431262 TI - Effect of catalase on regional cerebral blood flow and brain edema during the early phase of experimental pneumococcal meningitis. AB - Previous studies have demonstrated that the radical scavenger superoxide dismutase completely blocked the increase of regional cerebral blood flow (rCBF), intracranial pressure (ICP), and brain water content during the early phase of experimental pneumococcal meningitis in the rat. To obtain information on the nature of the reactive oxygen species involved, the effect of catalase, a hydrogen peroxide scavenger, was tested. Rats injected intracisternally with live pneumococci were either untreated or received intravenous catalase. The increase of rCBF and brain water content in infected untreated rats was significantly attenuated by catalase 6 h after intracisternal challenge. ICP increased in both infected groups, with a trend toward lower ICP with catalase treatment. Cerebrospinal fluid white blood cell counts were not significantly different between infected groups. These results and previous experiments using superoxide dismutase suggest that the increase of rCBF, ICP, and brain water content is mainly caused by superoxide or superoxide reaction products. PMID- 1431263 TI - Association of genital infection with specific Chlamydia trachomatis serovars and race. AB - Black race is an important risk marker for Chlamydia trachomatis genital infection. To define whether C. trachomatis serovars differ by ethnic distribution, a panel of monoclonal antibodies was used to serotype 934 urethral and 581 cervical isolates from patients attending a sexually transmitted diseases clinic over 2 years. The overall serovar distribution in cervical and urethral infections was comparable, with B class serovars predominating. Significantly higher inclusion counts were observed both in younger women and in nonblacks regardless of serovar. Serovar D was less frequent among blacks at the urethral site (P = .001), while serovar Ia was more frequent in blacks at both sites (urethral, P < .001; cervical, P = .02). These associations remained significant after adjusting for age and number of inclusion-forming units by multivariate analysis. Thus, specific serovars may be associated with particular racial groups; either behavioral or biologic factors could explain these findings. PMID- 1431264 TI - A subpopulation of Treponema pallidum is resistant to phagocytosis: possible mechanism of persistence. AB - While untreated syphilis infection is characterized by spontaneous resolution of early lesions, a few organisms evade the host immune response and persist for many years. Macrophages are generally recognized as the effector cell responsible for bacterial clearance, and phagocytosis is enhanced by immune serum. This study examined the susceptibility of Treponema pallidum isolated at various stages of lesion resolution to opsonization and phagocytosis by macrophages in vitro. Findings suggest that the population of organisms remaining after the majority of bacteria have been cleared in vivo is resistant to phagocytosis. This may provide a mechanism for the persistence of T. pallidum in the face of an otherwise active immune response. PMID- 1431265 TI - Antigenicity of a protective recombinant filarial protein in human bancroftian filariasis. AB - A 92-kDa fusion protein that encodes amino acids 1-479 of a 62-kDa Brugia malayi antigen induces resistance to microfilariae in mice. The antigenicity of this recombinant protein was explored in asymptomatic residents of Wuchereria bancrofti-endemic areas of Papua New Guinea and Egypt. Unlike sera from individuals in nonendemic areas, sera from residents of endemic areas contained IgG3 antibodies (up to dilution 1:1280) reactive with the fusion protein. There was little or no recombinant antigen-specific IgG1, IgG2, IgG4, or IgE. The mean level of IgG3 antibodies to the amino acid 1-479 construct in sera of putatively "immune" adult Papua New Guineans and children in whom microfilaremia was < 4 parasites/mL of blood was not significantly different (P < .05) from those with > 1000 parasites/mL. These data indicate that the filarial antigen corresponding to the recombinant protein is highly immunogenic in naturally infected children and adults and that the isotype and magnitude of antibody reactivity with it do not correlate with the microfilaremic status of asymptomatic persons. PMID- 1431266 TI - Malnutrition and immunity. PMID- 1431267 TI - Smear-negative cerebral malaria due to mefloquine-resistant Plasmodium falciparum acquired in the Amazon. PMID- 1431268 TI - Impaired humoral immunity is associated with development of methicillin-resistant Staphylococcus aureus infections after esophageal surgery. PMID- 1431269 TI - Type-specific anti-pneumococcal antibodies in a vaccinated patient with combined immunoglobulin A and IgG2 deficiency and invasive pneumococcal infections. PMID- 1431270 TI - Inhibition of the Salmonella typhi oral vaccine strain, Ty21a, by mefloquine and chloroquine. PMID- 1431271 TI - Seropositivity to Trypanosoma cruzi in blood donors in Santa Cruz, Bolivia. PMID- 1431272 TI - Falciparum malaria modulates viremia in chronic hepatitis B virus infection. PMID- 1431273 TI - External morphology of the sperm of Hyalomma marginatum (Acarina: Ixodidae). AB - Mature sperm cells of the tick Hyalomma marginatum were studied by means of scanning electron microscopy. The cell tapering end is transformed into a hemispherical structure. The rest of the cell surface is covered by longitudinal cellular processes, at the tip of the tapering end of the sperm cell an invaginated acrosomal canal can be seen. PMID- 1431274 TI - Transplacental transfer of schistosomal antigens and antibodies. AB - Circulating S. mansoni soluble antigens (CSA) and antibodies (CAB) were investigated in sera of 32 S. mansoni-infected pregnant mothers, their 32 newborns and 26 non-pregnant infected women. CSA levels in pregnant mothers and their newborns were significantly higher than in the 3rd group. Also, a significant positive correlation was detected between the CSA levels in sera from infected mothers and the cord blood of their newborns proving the transplacental transfer of these antigens. On the other hand, CAB levels were significantly higher in the 3rd group than in the mothers and their newborns and this could be explained by the immune complexes formation. No schistosome eggs or worms were detected in placentas and the possibility of congenital schistosomiasis was eliminated. PMID- 1431275 TI - Isospora solimanae sp. nov. from the Egyptian hoopoe (Upupa epops major). AB - Isospora solimanae (sp. nov.) is recorded for the first time infecting the Egyptian hoopoe (Upupa epops major). Unsporulated as well as sporulated oocysts were studied, photographed and compared with other isosporan infections of related birds. Site of infection and invasion limits were determined among naturally infected hoopoes and represented diagramatically. The rate of infection was congruent to 37.5%, and its severity considered to be non-pathogenic, since no remarkable lesions were observed. No extra-intestinal site of parasite development was recorded. PMID- 1431276 TI - Estimation of Toxoplasma gondii antibodies in patients with cardiomyopathy. AB - The possible involvement of Toxoplasma gondii in the pathogenesis or as a complicating factor in patients with cardiomyopathy has been investigated by the serological detection of specific antibodies by IFAT. Fifty six serum samples were collected from patients who presented with dyspnoea on effort, pericardial pains, palpitations and oedema of lower limbs. They were investigated by Echo, ECG and epidemiological history, and diagnosed as dilated, ischaemic and restrictive cardiomyopathies and myocarditis. Forty serum samples from patients with valvular lesions were examined as a control group. Twelve out of 56 samples were positive at end titre of 1:16 (21.4%). Sera with positive titres were found to occur mostly in patients with ischaemic cardiomyopathy. All samples of the control group were negative. PMID- 1431277 TI - Cutaneous leishmaniasis as a possible predisposing factor for skin malignancy. AB - This paper reports a 13 year old Yemenian boy with cutaneous leishmaniasis (CL.). The histopathological picture of the CL lesions showed marked dysplasia indicating premalignancy. The possibility that CL as one of the predisposing factors for skin malignancy was discussed. PMID- 1431278 TI - Dot-ELISA as a diagnostic test in hydatid disease. AB - Detection of circulating echinococcal antigens and antibodies were tried in 18 patients with hydatid disease and 32 healthy blood donors as controls using dot ELISA. Hydatid cyst fluid antigen and anti-echinococcal hyperimmune rabbit sera were used for the detection of antibodies and antigens respectively. The results proved that this test is sensitive (88.9%), specific (96.9%) and rapid for detecting echinococcal antibodies. On the other hand, circulating antigens could be detected with 55.6% sensitivity. This low sensitivity was attributed to the small amounts of circulating antigens and/or immune complexes formation. PMID- 1431279 TI - Investigation of Sarcocystis as a causative agent in cardiac disease. AB - Sera from 56 cases with cardiomyopathy and myocarditis and 40 cases with different types of valvular diseases were tested, using the indirect fluorescent antibody test (IFAT) for the detection of antibodies to Sarcocystis. None of the cases showed specific reaction where the IFAT was negative at the cut off titre 1:8 in all the cases. PMID- 1431280 TI - An acute case of infantile visceral leishmaniasis histopathological and histochemical studies. AB - Some histopathological and histochemical studies were carried out on the intestines of an acute case of infantile visceral leishmaniasis. Macrophages carrying amastigotes were seen mainly in the villous tips, mucin secretion inside the mucosal cells was mild, deposits of collagen and fibrin in the lamina propria were marked and the argentaffin cells were partially lost. The whole results were discussed. PMID- 1431281 TI - Studies on Eimeria species naturally infecting Gerbillus pyramidum (1) Exogenous stages. AB - Exogenous stages of two new Eimerian species, naturally infecting the Egyptian gerbil Gerbillus pyramidum were described and diagnosed in the present study. (1) The subspherical type of oocysts was 20 x 17 microns (length x width) in average. These are colourless and enveloped within an even double-layered oocyst wall. Sporulated oocysts containing four sporocysts each averaged in 10 x 8 microns, and a small spherical oocyst residual body was also observed. This type is termed Eimeria pyramidi after the species name of its host. (2) The second type of oocysts was elongated in shape measured congruent to 21 x 16 microns. These are colourless and enclosed within smooth double layered oocyst wall. Sporulated oocysts of this type were lacking oocyst residual bodies. This type is termed Eimeria gerbilli after the generic name of its host. Both types of described oocysts lack micropyle and polar cap. PMID- 1431282 TI - Assessment of left ventricular function by Doppler echocardiography in Egyptian bilharzial patients with or without pulmonary hypertension. AB - Forty-eight Egyptian bilharzial patients were selected for this study. Forty males and eight females. Their ages ranged from 12-60 years. All had hepatosplenomegaly with or without cardiopulmonary schistosomiasis. Also a group of ten subjects was chosen as a control group. After full clinical, laboratory and radiological examinations our subjects were subjected to: right cardiac catheterization, M-mode, two-dimensional as well as Doppler echocardiography. We found that the left ventricular geometry was distorted from its circular configuration as a result of right ventricular pressure overload as measured by the eccentricity index in bilharzial pulmonary hypertension. Also there were significant impairment of all Doppler echocardiographic parameters in those patients except time to E-peak (early diastolic flow velocity) and acceleration time of aortic flow (cm/sec2). PMID- 1431283 TI - Histopathological and histochemical studies on the sigmoidal and rectal tissues of hepatosplenic children with gastro-intestinal troubles. AB - Hepatosplenomegaly accompanied with different intestinal troubles is more or less a marked clinical manifestations in children. The histopathological and histochemical changes were studied in biopsied materials taken from the sigmoidal and rectal tissues of 49 children. These children had schistosomiasis mansoni (26), schistosomiasis and amoebiasis (4), schistosomiasis and tuberculosis (TB.) (2), amoebiasis (4), thalassemia (6), acute myeloid leukaemia (AML) (1), mucopolysaccharidosis (1) and bacillary dysentery (5). The pathological changes were erosion ulceration hyperplasia, atrophy, crypt-abscess and fibrosis (mucosa) and oedema, congestion, cellular infiltration (Lamina propria). The chemical changes were the mucin secretion, deposition of collagen and fibrin and activity of the argentaffin cells. Not all the disease agent had the same effect, but changes were marked mainly in children with S. mansoni and/or E. histolytica. PMID- 1431284 TI - Evaluation of different immunodiagnostic techniques for diagnosis of hydatidosis in Egypt. AB - In this study detection of the circulating hydatid antibodies was performed by three serological tests: Immunoelectrophoresis (IEP), Enzyme linked immunosorbent assay (ELISA) and Enzyme linked immunoelectrotransfer blot (EITB) technique. The antigen which was used in these tests was Echinococcus granulosus antigen free of host (camel) antigen by immunoaffinity chromatography. Most serum samples were pre-selected from the patients on the basis of clinical syndrome or past history of possible diagnosis of echinococcosis. In addition, physical aids to diagnosis, especially sonographic and plain X-ray examination have already been carried out. The hydatidosis group was subgrouped according to the site of the cysts in different organs. The surgical removal of hydatid cysts was taken as a sure diagnosis of hydatid disease. The outcome of comparison between the three serological tests in surgically confirmed cases, showed that ELISA technique is a good screening test (88.2% sensitivity, 88.8% specificity and 88.5% diagnostic efficacy) and EITB is a good confirmatory test (100% sensitivity, 100% specificity and 100% diagnostic efficacy). PMID- 1431285 TI - A study on experimental cryptosporidiosis. AB - Cryptosporidium oocysts were isolated from stools of infected patients diagnosed as cryptosporidiosis. Suckling Swiss albino mice were infected orally by these oocysts in a dose of 10(6) oocysts/mouse. Mice were divided into 9 groups according to the duration of infection 2, 3, 4, 5, 6, 7, 10, 10, 15, 21 days postinfection, corresponding non infected control groups were included. Stools of infected mice were examined twice daily to determine; infection rate, prepatent period and intensity of infection. Mice were sacrificed according to the schedule and the whole intestine was isolated and processed for histopathological examination by H & E and modified Ziehl Nielsen stain, and histochemical examination for acid and alkaline phosphatase activity. The results revealed that the infection rate was 90% and prepatent period 3-5 days and the course of infection was 21 days. The maximum pathological changes were in the ileum. These changes were reversible. PMID- 1431286 TI - Characterization of Egyptian isolates of Trichomonas vaginalis I. Isoenzyme patterns. AB - Three T. vaginalis isolates from Egypt were compared for their isoenzyme electrophoretic patterns on cellulose acetate. The enzymes studied were: glucose 6-dehydrogenase (G6PD); malate dehydrogenase (MDH); phosphoglucomutase (PGM); glucose phosphate isomerase (GPI); malic enzyme (ME); hexokinase (HK) and lactate dehydrogenase (LDH). The three isolates shared the same isoenzyme banding patterns of MDH; GPI; HK and LDH. Two of these isolates were similar in their banding patterns of G6PD, PGM and different from those of the third isolate. The latter was similar to one of the two isolates and different from the other in the ME isoenzyme patterns. PMID- 1431287 TI - Comparative studies on the production of invasive larvae of Steinernema feltiae Filipjev nematodes within insect host. AB - A comparative study has been made on the production of invasive larvae of Steinernema feltiae Filipjev within the cotton leafworm Spodoptera littoralis Boisduval and house fly Musca domestica Linnaeus. The results indicated that there is a positive correlation between the reproductive rate of invasive larvae and the initial dosages, host species and host stages. The reproductive rate of invasive larvae of Steinernema feltiae in Spodoptera littoralis imagos and caterpillars was higher than in M. domestica. At the pupal stages of M. domestica, no reproduction was obtained. Pupae were refractory to parasitism presumably owing to the effective protection afforded by the puparium. S. feltiae would be better adopted to live in S. littoralis than in M. domestica. PMID- 1431288 TI - Fine structure studies of microgametogenesis of Eimeria adenoeides (Eimeriidae, Sporozoa) infecting turkeys in Egypt. AB - The Ultrastructure of microgametogenesis of Eimeria adenoeides was studied in the intestinal epithelium of experimentally infected turkeys' Meleagris gallopavo gallopavo. Microgamonts were recognizable by the presence of peripherally arranged nuclei and the presence of two centrioles between each nucleus and the limiting membrane of the gamont. A nuclear spindle apparatus and an intranuclear centrocone directed toward the centriole were observed. Each young microgamont was surrounded by a very narrow parasitophorous vacuole which widened during development and contained a few intravacuolar folds. Differentiation of the microgamete began when elevations of the limiting membrane appeared above the centrioles. This event was accompanied by the segregation of nuclear content into a dense osmiophilic portion and an electron-pale portion. A gradual protrusion of the dense portion of the nucleus and developing flagella into the parasitophorous vacuole was proceeded. Microgametes had an anterior perforatorium, a dense elongate nucleus, with an anteriorly positioned mitochondrion in a small groove of the nucleus. Usually two flagella could be detected per each mature microgamete. PMID- 1431289 TI - Assessment of interleukin-1 activity of peritoneal macrophages in mice infected with Schistosoma mansoni before and after praziquantel administration. AB - This work was devoted to clarify the changes in interleukin-1 (IL-1) activity of peritoneal macrophages in mice experimentally infected with S. mansoni before and after praziquantel administration. A significant increase in (IL-1) activity after praziquantel administration was detected. These findings clarify the role of praziquantel in improving the immune state of the infected host. PMID- 1431290 TI - Ultrastructural features of the tegument of adult Cynodiplostomum azimi (Trematoda:Digenea) in experimentally infected albino rats. AB - The ultrastructure of the tegument of adult Cynodiplostomum azimi and the lesions caused by the worm at this host parasite interface in albino rats are described. The tegument consists of a syncytial distal cytoplasm (approx. 2.01-3.1 microns in thickness), bounded by an outer apical plasma membrane and an inner basal trilaminated lamina. The subtegumental cells (approx. 10.34 microns in length) are connected with the distal cytoplasm by means of cytoplasmic trabeculae. The morphology of the tegument appeared very variable. Large areas were formed of irregular folds, while other areas carried finger-like or papilla-form structures. Tegumental spines appear to have a crystalline lattice structure. Three morphologically distinct types of membrane-bound inclusion bodies were described in the tegumental/perikaryal complex. The electron-lucent elongate bodies (approx. 0.23 micron in length) were the predominant first type. The second was round-ovoid bodies (average length 0.12 micron) with a central core of electron-dense material. The third was electron-dense, rod-like in shape (0.28 micron in length) and occurred occasionally. The majority of these inclusion bodies were oriented parallel to the tegumental surface. The host's mucosa at the parasite interface showed marked flattening and partial to complete loss of mucosal microvilli. Inflammatory cells, particularly eosinophils were observed at the host-parasite interface. PMID- 1431291 TI - Study of human and parasitic factors in relation to bancroftian filariasis in Egypt. AB - The Human Leucocytic Antigen (HLA) and the histochemical reaction of microfilaria were studied by using cytotoxicity test and microfilarial acid phosphatase activity respectively to evaluate the role of the genetic factors and the parasitic factor in the pathogenesis of filariasis. Statistical significant association was found between HLA-B7 and the susceptibility for retaining microfilariae in blood and the development of clinical manifestations of filariasis. Histochemical study reported more or less the same results obtained in Egypt in elsewhere. PMID- 1431292 TI - Some biological effects of Bayluscide on Physa acuta and Helisoma duryi. AB - The fecundity, viability and the size of egg-masses were studied in Physa acuta and Helisoma duryi snails treated with 1 ppm Bayluscide for two hours. Bayluscide application caused significant and highly significant reduction in the fecundity of both Physa acuta and Helisoma duryi. However, an increase in the fecundity was observed for both treated snails in few days after exposure. Moreover, Bayluscide did not lead to stoppage of egg laying at any day of experiment. Bayluscide caused a reduction in the viability of egg-masses produced by treated Physa acuta or Helisoma duryi snails since they produced higher numbers of abnormal eggs containing dead embryo. Moreover, application of 1 ppm Bayluscide for two hours against Physa acuta caused a decrease in the size of egg-masses produced by treated snails. This is expressed by the production of higher percentage of egg masses containing small numbers of eggs as compared with those masses produced by control snails. PMID- 1431293 TI - Histo- and immuno-pathological and electron microscopy studies of the splenic red pulps of schistosomiasis mansoni patients. AB - The histo- and immuno-pathological and electron microscopy (EM.) of the splenic red pulps studies were carried out for schistosomiasis mansoni patients and normal controls. The main pathological processes were interstitial haemorrhages, congestion, proliferation and hyperplasia of the red pulps of the schistosomiasis mansoni patients. The IgG showed marked reaction, moderate with IgA and mild with IgM. The E.M. showed an increase in the size of the different types of the reticular cells particularly those of the nuclear membrane with type II, nuclear degeneration, deposition of fibrin threads, marked fibrosis and phagocytosis and formation of pores at the sinusoidal basement membrane. It was concluded that these pathological processes and the alteration in the immunoregulatory system of the spleen of schistosomiasis mansoni patients reflect the role played and perpetrated in the development of splenomegaly. PMID- 1431294 TI - Immunological response to diphtheria/tetanus vaccine in Schistosomiasis mansoni patients. AB - The cellular and humoral immune responses of patients with S. mansoni infection were evaluated before and one month after each of two intramuscular doses of diphtheria/tetanus toxoid vaccine. Patients were divided into "responder" and "non-responder" groups based on anti-tetanus toxoid (anti-TT) IgG levels after vaccination. The specific anti-TT IgG1 response of the responder group was predominantly in the IgG, subclass. The lymphoproliferative response to PHA was also significantly higher in the responder group; this elevation was detectable before and after each vaccination. The responses to PWM and SPL were comparable in the two groups before vaccination, although the responder group had a higher response to SPL after vaccination. IgG antibodies for schistosome adult worm and egg antigens were significantly lower in the responder group prior to vaccination but not thereafter. Anti-diphtheria IgG antibodies were comparable in the two groups after vaccination at all times. Clinically, the non-responder patients had a higher incidence of splenomegaly (84.6% vs 44.8%) and were significantly older than the responder patients (mean 34.1 yrs vs 18.7 yrs). The cause for the reduced anti-tetanus IgG response in schistosomiasis patients is believed to be multifactorial. T cell or antigen presenting cell dysfunction, high levels of IgG antibodies specific for schistosome antigens, splenomegaly and age are factors that might lead to reduced anti-TT IgG response. PMID- 1431295 TI - Cyclosporin A in experimental trichinosis scanning electron microscopic study. AB - The surface morphology of adult and larvae of Trichinella spiralis after cyclosporin A treatment was studied by scanning electron microscopy (SEM) of fixed, dried and metal coated specimens. The earliest topographic changes revealed in adults after the drug treatment were in form of disorganization of the cuticle especially between the hypodermal pores which appeared somewhat thickened and irregular. Other changes were in form of bullae formation covering the whole width of the adult surface. Other specimens showed wrinkling of the outer layer that was seen later to peel off. In few worms layer outer was damaged releasing some of the internal organs. Smoothing of the cuticle with obliteration of the grooves between the cuticular ridges were observed as the earliest surface larval changes, ulcer formation which was deeply seated was seen in patchy areas in some specimens. The interaction between the parasite surface and the drug is of significant importance as this can throw light on the possibilities of its mode of action. PMID- 1431296 TI - Characterization of Egyptian isolates of Trichomonas vaginalis: I. Serotyping. AB - Antitrichomonal hyperimmune sera against T. vaginalis stocks isolated from Egyptian female patients were employed for serological differentiation of somatic and soluble antigens in the Ouchterlony gel double immunodiffusion technique. It was concluded that soluble trichomonal antigens present in association with living flagellates are stock--specific reacting with some, but not all the antitrichomonal hyperimmune sera, while those present in association with dead parasites are common antigens reacting with all the sera. Three stocks, E1, E2 and E3 could be differentiated into two strains using their stock--specific antigens. The somatic antigens of six trichomonal stocks reacted with all the hyperimmune sera denoting common antigenic make up. PMID- 1431297 TI - Studies on flea fauna in El Fayoum Governorate, Egypt. AB - This paper dealt with the studies of flea fauna as collected on the rodent hosts over one year. The collected rodents (499) in a descending order of abundance in the collection were Rattus rattus, R. norvegicus, Mus musculus, Gerbillus pyramidum and Arvicanthis niloticus. The collected fleas in a descending order in the collection were X. cheopis, P. irritans, N. jasciatus, C. felis, L. segnis and E. gallinacea. The total flea index reached the maximum (0.76) in May and it was zero in December and January. The highest number of fleas was on R. norvegicus and A. niloticus and the lowest was on G. pyramidum. The highest number of rodents and their flea ectoparasites was during the Spring and the lowest was during Autumn. The medical importance of the collected fleas and the whole results were discussed. PMID- 1431298 TI - On the morphology of the oxyurid nematode Pharyngodon mamillatus (Linstow, 1897) from Chalcides ocellatus from Egypt. AB - The nematode P. mamillatus is described from the lizard Chalcides ocellatus (Forsk.) from Cairo, Egypt. The use of both light and scanning electron microscopy enabled the authors to report new morphological features of the worms, including the cuticular surface, lateral alae and male caudal structures. PMID- 1431299 TI - Studies on chronic liver diseases in patients with and without Toxoplasma latent infection. AB - Chronic liver diseases mainly due to schistosomiasis is a common clinical feature in Egypt. On the other hand, Toxoplasma latent infection is another common feature. In this paper, it was aimed to study the role of Toxoplasma latent infection in patients with chronic liver diseases mainly due to schistosomiasis. The latent Toxoplasma infection was measured by the positivity of IgG to ELISA and the negativity of IgM to DS-ELISA. The cellular immunity was assessed by the dinitrochlorobenzene (DNCB) skin test. The clinical and the laboratory studies showed that latent Toxoplasma infection had no marked effect on the progression of the chronic liver diseases. PMID- 1431300 TI - Ultrastructural study of the tegument of Cotugnia polyacantha and Killigrewia streptopelia inhabiting the dove Streptopelia senegalensis aegyptiaca. AB - The ultrastructure of the teguments of the cyclophyllidean cestodes Cotugnia polyacantha and Killigrewia streptopelia naturally infecting the dove Streptopelia senegalensis aegyptiaca, was studied using transmission electron microscopy. The two cestodes inhabit two distinct sites in the small intestine of the same bird. Observations revealed basic similarity between the two cestodes, though, marked differences between the tegument structure details of the two species regarding the structure and dimension of microtriches, types and distribution of vesicles among the regions of the tegumental/perikaryal complex, structure of subtegumental connective tissue and subtegumental muscle layer. The significance of these observations was discussed in possible relation to the different physico-chemical environments known to occur where each cestode resides. PMID- 1431301 TI - Ultrasonographic findings in the gall bladder in human fascioliasis. AB - This study included forty patients with incubating or open fascioliasis. All were subjected to repeated stool examination, serological and haematological study using IHAT in the former. Ultrasonography was done for upper abdomen stressing on gall bladder and assessing its function. Eighteen patients were diagnosed as incubating fascioliasis by positive IHAT, high eosinophilic count and negative stool examination for Fasciola eggs. No gall bladder changes could be detected by U.S. among those patients. Twenty two patients passed eggs in their stool were diagnosed as open Fasciola. Their gall bladder through U.S. revealed flukes in twelve of them. A weak gall bladder contractility was observed in 64% with open fascioliasis. PMID- 1431302 TI - The effect of scorpion envenomation on the different organs of albino mice. AB - The effect of sublethal doses of scorpion venom (Buthus quinquestriatus) on the hepatic vascular bed and hepatic parenchyma were studied. The main toxic effect of the venom was primarily on the vascular bed of the liver as manifested by dilatation of branches of the hepatic artery, portal vein together with intravascular thrombi and subcapsular haemorrhages. Apart from mild hydropic degeneration some cells of the hepatic parenchyma showed focal necrosis and Kupffer cells were frequently hypertrophied and contained pigment. In the lung, dilated thrombosed vessels were observed. In the kidney, the vessels showed the same changes. The epithelial and endothelial cells of the glomeruli appeared normal except for slight swelling with intact basement membrane. The tubular cells were swollen with increased granularity and attenuation of the tubular lumen, a picture compatible with hydropic degeneration. The possible mechanisms in inducing such lesions were discussed. PMID- 1431303 TI - Evaluation of insecticidal efficiency of certain new selective formulations against Musca domestica (L). AB - Five new selective formulations were tested for effectiveness, applicability and costs in controlling the housefly Musca domestica. The tested formulations are Alfacron SB, Alfacron 10 WP, Snip IRB (a.i. Azamethiphos, thiophosphorester), Baygon SB and Golden Marlin Results of laboratory studies revealed that Alfacron 10 WP was the most potent compound against the adult fly (100% mortality was achieved after 20 min from exposure). Snip IRB ranked second with 100% mortality after 40 min, followed by Alfacron SB (50 min.) and Golden Malrin (60 min.). On the other hand Baygon SB did not show complete mortality of houseflies since its maximum mortality was 57.5% after 60 min. Laboratory tests also proved that moistening the fly prolonged the efficacy period of the three tested products from 3 to 6 weeks in case of Alfacron SB, from 4 to 7 weeks for Snip IRB and from 7 to 9 weeks in case of Alfacron 10 WP. PMID- 1431304 TI - Comparative evaluation of antigens used in immunofluorescence (IFAT) antibody test for serodiagnosis of schistosomiasis. AB - The diagnostic value of antigens used in the IFAT for serodiagnosis of schistosomiasis has been evaluated. Cryosections of Schistosoma mansoni adults, formaline fixed cercariae and cryosections of infected liver, from gold hamster, which contained granuloma were used as antigens in this evaluation. The cryosections of adult worm were more reliable and more specific as an antigen for immunofluorescence (Diagnostic efficacy was 95.52%). The cercarial antigens gave the same results as the cryosection of adults. The IFAT using cryosection of infected liver contains granuloma was less reliable due to autofluorescence of eggs in the granuloma with negative sera (Diagnostic efficacy was 49.01). PMID- 1431305 TI - Definition of receptor binding domains in interferon-alpha. AB - Earlier studies from this laboratory had identified three regions in interferon alpha (IFN-alpha) that influence the active conformation of the molecule. These domains are associated with the amino acid residues 10-35, 78-107, and 123-166. In this report, we define these domains more accurately by identifying their critical clusters of amino acids. Using a panel of IFN-alpha 2a variants in antiviral, growth inhibitory, and receptor binding studies, we are able to show that these three domains, defined by residues 29-35, 78-95, and 123-140, are likely located on the surface of the molecule, with domains 29-35 and 123-140 in close spatial proximity. We conclude that the 29-35 and 123-140 domains are responsible for IFN-alpha receptor binding interactions and constitute receptor recognition sites in IFN-alpha. Extrapolating from our biological activity data, in the context of a number of predictive algorithms that provide insights into the hydrophobicity/hydrophilicity, surface probability, and flexibility of amino acid clusters, we infer that the residues 29-35 influence the active configuration of IFN-alpha most significantly. This region likely represents a loop structure that is relatively rigid in configuration. The carboxy-terminally located strategic domain, 123-140, is comprised of two clusters of amino acid residues, one that forms part of a rigid alpha-helix, the other a more flexible loop structure. Similarly, the 78-95 domain comprises a portion of an alpha helical structure that is followed by a loop structure. Close examination of the amino acid sequences in all three regions among the different species of IFN alpha s and human IFN-beta indicate that the 29-35 and 123-140 domains are most highly conserved, yet some variance is apparent in the 78-95 domain. We propose that the 78-95 region influences species specificity among the murine and human IFN-alpha s and determines the differential specificity of action between human IFN-alpha and human IFN-beta. PMID- 1431306 TI - Interferon-alpha suppresses the capacity of T cells to help antibody production by human B cells. AB - This study was designed to analyze the effect of interferon-alpha (IFN-alpha) on the potential of T cells to help B-cell differentiation in vitro. Human splenic T cells preactivated via the T-cell receptor (TCR)/CD3 complex, as well as murine EL4 thymoma T cells preactivated with phorbol esters, stimulated human B cells via a species cross-reactive physical interaction to differentiate into antibody producing cells. If the human or murine T cells were activated in the presence of IFN-alpha, normal proliferation and interleukin-2 (IL-2) production occurred, but the cells did not acquire any B-cell helper potential. Therefore, IFN-alpha modulates the B-cell stimulatory potential of T cells by interfering with the T cell activation process. In contrast, IFN-alpha neither acted on B cells directly nor on already activated T cells, because it did not suppress B-cell differentiation induced by T cells preactivated in the absence of IFN-alpha. IFN alpha did not induce the production of inhibitory T-cell factor(s), since T cells preactivated in the presence of IFN-alpha did not inhibit the interaction of B cells with T cells optimally preactivated in the absence of IFN-alpha. Taken together the data indicate that IFN-alpha suppresses the potential of T cells to stimulate B-cell differentiation by interfering with the T-cell activation process, but acts neither on B cells directly nor on already activated T cells. PMID- 1431307 TI - Constitutive production of interferon-alpha 2 by a human B-lymphoblastoid cell line. AB - Human B-lymphoblastoid cell lines immortalized by Epstein-Barr virus constitutively produce low levels of acid-stable interferon (IFN) that differs in composition from IFN produced by the same cell type after virus induction. We use three approaches to study the constitutive IFN produced by the lymphoblastoid cell line, LuKII: (i) antiviral bioassays with a neutralizing monoclonal antibody; (ii) amino-terminal sequence analysis of the single protein obtained after purification of the IFN by immunoaffinity chromatography and reverse-phase HPLC; (iii) sequence analysis of cDNA clones obtained by screening a LuKII library with an IFN-alpha 2 probe. Our data show that more than 90% of the constitutive IFN results from expression of a single gene coding for IFN-alpha 2. The significance of these results is discussed. PMID- 1431308 TI - Different interactions of interferon-alpha subtypes at the surface of epithelial and lymphoid cells. AB - The interaction of different interferon (IFN)-alpha subtypes with different cell types was investigated using a unique monoclonal antibody (MAb), I-4-A. This MAb reacts in immunoassays equally with IFN-alpha 2b and IFN-alpha 4a, but does not inhibit the binding of IFN to cell receptors. 125I-labeled I-4-A reacted with IFN alpha 4a and IFN-alpha 2b bound to receptors on Daudi cells. However, in a "double assay" developed using Daudi cells to measure antiviral and antiproliferative activity, I-4-A neutralized both activities of IFN-alpha 4a, but neither of IFN-alpha 2b. Similarly, in studies on the activation of natural killer (NK) cells, I-4-A neutralized the effect of IFN-alpha 4a but not that of IFN-alpha 2b. In contrast, when cell lines other than lymphoid were studied, e.g., HEp 2 and WISH cells, I-4-A neutralized the antiviral activity of both IFN alpha subtypes. The neutralization of one IFN-alpha subtype but not another on lymphoid cells suggests a difference either in the receptor-bound form of the subtypes, or in subsequent interactions prerequisite for activation of these cells. Furthermore, the neutralization of a particular IFN subtype, alpha 2b, on epithelial-derived but not lymphoid cells suggests differences in the IFN receptor complex or the mechanisms of cell activation between these cell types. An implication from these studies is that some IFN-alpha subtypes can exert different functions on lymphoid and epithelial cells. PMID- 1431309 TI - The effects of interferon-gamma and bacterial lipopolysaccharide on CD14 expression in human monocytes. AB - CD14 has been reported to be the lipopolysaccharide (LPS)-LPS binding protein receptor. The effects of interferon-gamma (IFN-gamma) on CD14 expression have not been clearly established. The purpose of this investigation was to examine the effects of IFN-gamma alone and IFN-gamma followed by bacterial LPS on CD14 expression. Human peripheral blood monocytes were isolated by counterflow centrifugal elutriation (CCE). Monocytes were cultured for 48 h with IFN-gamma alone or for 24 h with IFN-gamma followed by LPS for a second 24 h. IFN-gamma alone caused a down-regulation of CD14 expression, as assessed by flow cytometry, relative to CD14 expression in untreated monocytes. In addition, CD14 expression was even more significantly down-regulated after IFN-gamma pretreatment followed by either Prevotella intermedia or Salmonella typhimurium LPS. Likewise, the percentage of CD14+ monocytes decreased after IFN-gamma alone and even more dramatically after IFN-gamma treatment followed by either LPS. This study clearly demonstrated that IFN-gamma down-regulates CD14 expression and that LPS following IFN-gamma pretreatment potentiates this effect. PMID- 1431310 TI - Post-transcriptional regulation by interferon-alpha of epsilon-globin production in human erythroleukemia K-562 cells. AB - Treatment of human K-562 erythroleukemia cells with interferon-alpha (IFN-alpha) resulted in a six-fold increase in the production of epsilon-globin, a component of embryonic hemoglobin, but in a two-fold or less augmentation of the production of other globin species. There was no comparable increase in the production of epsilon-globin mRNA following IFN treatment. We did, however, observe a shift in the cytoplasmic location of the epsilon-globin mRNA from the messenger ribonucleoprotein (mRNP) to the polysome fraction after IFN-alpha addition. No such shift was noted in the location of the mRNA for A gamma-globin, the major globin product of K-562 cells, which was always present in the polysome fraction. These results are significant with respect to the mechanisms of cellular regulation and differentiation induced by IFNs. PMID- 1431311 TI - Identification of a complex formed between nuclear proteins and the transcriptional enhancer of interferon-inducible genes that is present in the peripheral blood myeloid cells of CML but not normal individuals. AB - Interferon-alpha (INF-alpha) induces cytogenetic remissions in 20% of chronic myelogenous leukemia (CML) patients. To clarify the mechanisms through which this antiproliferative action of IFN is mediated in the CML cell, a modification of the mobility-shift assay was used to follow the formation of complexes between nuclear proteins and IFN-inducible transcriptional enhancers involved in mediating the cellular effects of IFN-alpha. These studies identified a complex that was present in the myeloid cells of 18/24 (75%) of chronic-phase CML patients tested whose cells contained 100% Philadelphia chromosome positive (Ph+) cells, while the proteins of none of the samples tested from normal peripheral blood samples and only 22% (2/9) of the CML patients in an IFN-induced major cytogenetic remission (less than 30% Ph+ cells) contained these complexes. These studies suggest that the mobility-shift assay detects changes in the CML myeloid cell that distinguish it from the normal myeloid cell. PMID- 1431312 TI - Double-blind randomized phase I study on the clinical tolerance and biological effects of natural and recombinant interferon-beta. AB - The clinical tolerance of and the effects recombinant human interferon-beta (rHuIFN-beta) obtained from mammalian cells (Chinese hamster ovary cells) exerts on 2',5'-oligoadenyl (2-5A) synthetase activity, human-Mx protein, neopterin, beta 2-microglobulin, interleukin-1 (IL-1) alpha and beta synthesis were compared to those of natural IFN-beta in 12 healthy volunteers. Each subject received a single i.m. injection of 6 x 10(6) IU rHuIFN-beta and natural IFN-beta according to a randomized double-blind cross-over study design. Both were well tolerated and provoked similar changes in clinical indices. Moreover, rHuIFN-beta and natural IFN-beta induced significant and similar increases in 2'-5' adenylates, human Mx protein, and neopterin levels, but neither modulated beta 2 microglobulin, IL-1 alpha or beta synthesis. The sum of these findings indicates that rHuIFN-beta and natural IFN-beta are biologically equivalent. In view of these results, we are of the opinion that these two types of IFN are probably also therapeutically equivalent and, in consequence, that trials to evaluate the response of viral and neoplastic disease patients to rHuIFN-beta are fully justified. PMID- 1431313 TI - Human interferons-alpha inhibit the production of immunoglobulin M by secreting and nonsecreting lymphoblastoid cell lines. AB - It is well known that human lymphoblastoid interferon-alpha [HuIFN-alpha(ly)] may either increase or decrease antibody production by B cells, in vivo as well as in vitro, depending on the experimental conditions and the system used. We compare here the effect of HuIFN-alpha(ly) and human recombinant interferon-alpha (rHuIFN alpha) on immunoglobulin M (IgM) production by secreting and nonsecreting human B like lymphoblastoid cells, respectively, ST8246, and Daudi cells. Under our experimental conditions, Daudi cells were less sensitive to the antiproliferative effect of IFN than previously reported by other authors, and ST8246 cells were insensitive to this antiproliferative effect. In contrast, IgM production was profoundly affected in both cell lines. Thus, we could discriminate between the effect on cell growth from the effect on the immune response. Using high-pressure liquid chromatography (HPLC) separation, mu chains and monomeric and pentameric IgM were distinguished from cytosolic and membrane-associated fractions and from culture medium (extracellular IgM). Pentameric extracellular IgM and monomeric membrane IgM were diminished by HuIFN-alpha(ly) treatment, respectively, in ST8246 cells and in Daudi cells. We conclude that HuIFN-alpha(ly) induces regression of B-like lymphoblastoid cells toward a less mature phenotype. PMID- 1431314 TI - Induced and down-regulated proteins in the human cultured hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi during incubation with interferon-alpha: a kinetic study. AB - To elucidate the mechanism of action of interferon-alpha (IFN-alpha), the effect on cell proliferation and protein synthesis in the human hairy cell leukemia line JOK-1 and the Burkitt's lymphoma cell line Daudi were investigated. While Daudi cells were inhibited in proliferation and in total protein synthesis, no effect was seen on JOK-1 cells. However, high-resolution two-dimensional gel electrophoresis showed that four polypeptides were induced in JOK-1 cells after IFN-alpha incubation, while an additional 11 were induced and two down-regulated in Daudi cells. Kinetic studies revealed that the changes in JOK-1 cells were only temporary (within 8-16 h) and small to moderate in magnitude (less than four fold). In Daudi cells, the changes for two of these polypeptides were early (within 2 h), for most of them prolonged (at least 24 h), and for three of them of great magnitude (between 6- and 30-fold). Quantitative analytical assessments indicated that four IFN-alpha-inducible polypeptides, present in low amounts of untreated cells, were highly expressed only in sensitive Daudi cells upon IFN alpha treatment. This observation might indicate a role for these polypeptides in the inhibition of cell proliferation in Daudi cells. Furthermore, six of the other IFN-alpha-modulated polypeptides were synthesized constitutively in JOK-1 cells at levels comparable to those achieved in IFN-alpha-treated Daudi cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431315 TI - Interferon-alpha activates binding of nuclear factors to a sequence element in the c-fos proto-oncogene 5'-flanking region. AB - Interferon-alpha (IFN-alpha) can regulate the expression of the c-fos proto oncogene in different cell types. Here we show IFN-alpha-activated binding of murine and human fibroblast nuclear factors to a DNA sequence element located in the 5' upstream region (nucleotides -351/-337) of the c-fos gene. This element, like the conserved enhancer element, the IFN-stimulated response element (ISRE), that mediates transcriptional induction of IFN-alpha-inducible genes, also binds factors in response to platelet-derived growth factor (PDGF) and v-sis conditioned medium (SCM). The IFN-inducible ISRE shares an 8-bp stretch of sequence homology with the IFN-responsive c-fos SCM element, and competes efficiently for binding of factors to the SCM. Protein-DNA cross-linking experiments with the SCM binding site identified an IFN-modulated nuclear protein of approximately 98 kD. This protein does not appear to be involved in transcription activation, since IFN-alpha failed to stimulate c-fos transcription in nuclear run-off assays, or the c-fos promoter in transient transcription assays of 3T3 fibroblasts. Our data nonetheless suggest the c-fos promoter may be an early target for signal transduction triggered by IFN alpha-receptor interaction. PMID- 1431316 TI - Opposite sensitivity to the antiproliferative action of interferon-alpha and granulocyte-macrophage colony-stimulating factor in monoblastic U937 cells. AB - Three variants of the human monoblastic cell line U937 with different degrees of sensitivity to the antiproliferative action of interferon-alpha (IFN-alpha were examined for phenotypic differences. The highly IFN-sensitive variant U937-V expressed twice as many IFN-alpha binding sites as both its IFN-alpha-resistant derivative U937-VR and the cell line U937 exhibiting a 20-fold reduction in IFN alpha sensitivity as compared to U937-V cells. All three variants were IFN reactive with regard to induction of 2',5'-oligoadenylate (2-5A) synthetase activity and were similarly sensitive to the growth-inhibiting action of IFN gamma and tumor necrosis factor. Responsiveness to the antiproliferative effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), however, was confined to cell lines U937 and U937-VR. Although expressing a comparable number of GM-CSF receptors, the highly IFN-sensitive variant U937-V was refractory to GM CSF. Flow cytometry revealed a marked difference in the expression of the antigen CD11b which was detectable on 85% of cells of the U937-V line but only on approximately 25% of cells derived from the U937 and U937-VR lines. Results thus demonstrate opposite sensitivity of U937 cells to the growth-inhibiting action of IFN-alpha and GM-CSF, apparently dependent on the state of U937 differentiation as determined by expression of the CD11b antigen. PMID- 1431317 TI - Tandem repeat polymers of a critical region of the human interferon-beta promoter exhibit a marked constitutive activity and enhanced responsiveness to transcriptional regulators in transfected HeLa cells. AB - Multiple copy tandem repeats polymers of an authentic 30-bp region of the human interferon-beta (IFN-beta) promoter between positions-91 to -62 relative to the cap site or the hexanucleotide GAAAGT derived from this region, both acted as strong constitutive regulatory elements in transfected HeLa cells. Such polymers were unresponsive to treatment with IFN-alpha despite their considerable homology with the IFN-responsive elements of other genes but were highly responsive to treatment of HeLa cells with IFN-gamma. Virus induction of HeLa cells transfected with polymers of the 30-bp region linked to a CAT gene increased the activity of the reporter gene 500- to 2,000-fold over baseline levels. Treatment with IFN alpha prior to virus induction did not increase further CAT activity. Cotransfection of HeLa cells with the CAT gene under the control of a 12-element tandem repeat polymer of the human IFN-beta promoter and an expression vector for the IRF-1 transcriptional activator markedly increased CAT activity while cotransfection of HeLa cells with the IFN-beta construct together with an expression vector for the transcriptional regulator IRF-2 markedly decreased CAT activity relative to cells transfected with the IFN-beta polymer alone. PMID- 1431318 TI - Ultrastructural study of mouse dorsal root ganglion cultures infected long term with M. leprae. AB - Ultrastructural changes in the mouse dorsal root ganglion cultures infected long term with viable M.leprae were studied. Subtle cytomorphological changes and loss of neurites noted in the long-term infected cultures were correlated to early events in the nerve damage. PMID- 1431319 TI - Treatment of paucibacillary leprosy with a regimen containing rifampicin, dapsone and prothionamide. AB - Ninety paucibacillary leprosy patients having indeterminate (I), tuberculoid (TT) and borderline tuberculoid (BT) type of leprosy with bacterial index (BI) of less than two on the Ridley scale were treated with rifampicin (RFM) 600 mg once a month, dapsone (DDS) 100 mg daily and prothionamide (PTH) 250 mg daily. Treatment was stopped at the end of six months. The patients tolerated the drugs fairly well and in only two patients the drugs had to be stopped (in one due to jaundice and in the other due to gastric intolerance). About 6% of patients had early reactions which subsided with additional steroid therapy. The inactivity rate was 60% at six months and this improved to 96% at 12 months. No cases of late reactions and relapses were encountered in the limited follow-up period of six months; and a longer follow-up is necessary for ascertaining the relapse rates. The preliminary results however suggest that the addition of prothionamide to the standard WHO paucibacillary regimen is well-tolerated with increased inactivity rate and fewer instances of late reactions. PMID- 1431320 TI - A comparative KAP study of leprosy patients and members of the community in Hlaing and Laung-Lon townships. AB - A KAP study was conducted in the peri-urban Hlaing and rural Laung-Lon Townships in Myanmar. It was found that both the leprosy patients as well as community members were still not sure about the cause of leprosy. Social stigma of leprosy encountered by patients needs to be addressed especially in peri-urban areas. It was also found that the patient's understanding of treatment regularity was still very unsatisfactory, for which health education measures needs to be introduced. PMID- 1431321 TI - Leprosy of the tongue. AB - Ten out of the twenty-five lepromatous leprosy patients studied showed clinical evidence of involvement of the tongue, and they presented with various symptoms like loss of taste, stiffness of tongue, bleeding, pain etc. Various types of lesions ranging from small nodule to granuloma formation, ulceration, macroglossia and fissured cracked tongue were noted. The tongue lesions were found to be related to the severity of leprosy. PMID- 1431322 TI - Correlation between inhibitory effect of quinolones and mycolic acid metabolism in mycobacteria. AB - Mycolic acids are important components having a significant role in maintaining the rigidity of mycobacterial cell wall. They could also be the barrier for penetration of certain drugs into the bacterial cell. A novel in vitro model system was established for assessing the effect of Ciproflaxacin on mycolic acid metabolism in pathogenic mycobacteria M. Kansasii (which has similar mycolic acid pattern to that from M. leprae) and the effect of norfloxacin in M. intracellulare. These test mycobacteria were exposed in their midlogarithmic phase of growth to 0.5, 1, 2, 3, 4, 5 and 6 micrograms ml of ciprofloxacin and norfloxacin respectively for 1, 2 and 24 hours. Ciprofloxacin completely inhibited the synthesis of mycolates in M. kansasii at 3, 4 and 5 micrograms/ml; whereas norfloxacin exhibited its maximum inhibitory action on mycolic acids in M. intracellulare at 6 micrograms/ml for all the durations of exposure. Inhibition of mycolates directly correlated with bacterial viability which was estimated by colony forming units. The effect of quinolones on mycolic acid metabolism appears to be direct and not secondary to DNA gyrase. The results obtained from this study and our previous findings show that mycolic acid metabolism is affected by various groups of drugs, whose primary sites of activity may be different. The findings of the present study may have significant therapeutic implications in leprosy and other mycobacterial diseases. PMID- 1431323 TI - Observations on the cultivation of M. leprae and M. tuberculosis in medium 'V' and 'V 1'. AB - Skin scrapings from five different active sites were collected from 14 leprosy patients and inoculated into medium V. Skin scrapings from three leprosy patients were inoculated into medium V 1. All the cultures were incubated at 8-10 degrees C. M. tuberculosis H37Rv, pretreatment isolates and streptomycin resistant strains were inoculated into medium V, with and without antibiotics, and incubated at 8-10 degrees C as well as 37 degrees C. Smears were made from the M. leprae and M. tuberculosis cultures at 0 hours and at different time points. The number of bacilli in the smears were counted. There was no increase in the number of M. leprae or M. tuberculosis in any of the cultures. PMID- 1431324 TI - A project model for attempting integration of leprosy services with general health care services after the prevalence of the disease is reduced in the endemic districts on multidrug therapy for over five years. PMID- 1431325 TI - Leprosy immunopathogenesis and vaccine development. AB - The truly effective immunity against intracellular parasites, including mycobacteria, is mediated by monocyte/macrophages, and in the immunologically responding (resistant) host these phagocytes need minimal antigenic stimulus, specific or non-specific, to become activated and be microbicidal. T-cell mediated delayed hypersensitivity (DTH) causes tissue damage and destruction, which is particularly unwelcome in leprosy because of its nerve-damaging potential. Gamma interferon (INF-gamma), the terminal lymphokine of a DTH response, promotes mycobacterial survival and growth. There are T-cells (TH1 subtypes) that produce DH response either independent of, or, only partly dependent on INF-gamma; this type of DH peaking at 24 hours appears similar to the Jones-Mote type rather than to the tuberculin type of DTH peaking at 48-72 hours and is devoid of the necrotic component of tuberculin type of DTH. M. leprae antigens normally elicit this Jones-Mote type of DH. Suppressor T-cells are associated with a protective immune response, while helper T-cells mediating DTH are harmful. In view of this immunobiology, it would appear that pathogenic mycobacteria that generate a tuberculin type DTH response should not be used as immunogens in leprosy. PMID- 1431326 TI - Pattern of leprosy deformities among agricultural labourers in an endemic district: a pilot study. AB - A study of 1,338 leprosy affected agricultural labourers in an endemic district revealed that 12% had deformities. The patient's sex, type of disease, duration and educational status seemed to influence pattern of leprosy deformities. The patients continued working despite deformities in order to avoid financial dependence on their family members and loss of dignity. PMID- 1431327 TI - Phenobarbitone in the treatment of dapsone induced hyperbilirubinaemia. PMID- 1431328 TI - Leprosy in Albania. PMID- 1431330 TI - Experimental vs. natural plasmid gene transfer? PMID- 1431329 TI - Duration of MDT for paucibacillary leprosy. PMID- 1431331 TI - Child sponsorship programme to prevent dehabilitation. PMID- 1431332 TI - IAL--sponsored workshop on "Advances in laboratory techniques with reference to patient care in leprosy", Drug-Bhilai. Jan. 5th 1992. PMID- 1431333 TI - International Gandhi Award 1992. PMID- 1431334 TI - Introduction to the CEA family: structure, function and secretion. AB - Due to the phenomenal progress in the field of tumor immunology that took place during the last twenty years, we dispose today of highly specific and sensitive techniques and reagents like monoclonal antibodies (MAbs). In this context the discovery in human carcinomas of tumor-associated antigens, such as CEA, was of primary importance, especially since the latter was found to have clinical relevance as a tumor marker. Based on animal models, a new in vivo technology for the detection of tumors and metastases was developed in recent years, that uses anti-CEA MAbs, or fragments of them, coupled to radio-isotopes. This technique, called radio-immunodetection (RAID), also paved the way for immunotherapeutic procedures, where again CEA served as the target-antigen. This new technique holds great promise, provided the epitope-specificity of the MAbs is well controlled: it has been shown that CEA belongs to a large gene-family of at least 22 members, which can be subdivided into two subgroups (i.e., the CEA- and the PSG-subgroup) and which in turn belongs to the immunoglobulin-supergene family. Great structural similarities render the distinction of the various cross reactive molecules by immunological means rather difficult. PMID- 1431335 TI - The CEA family: a system in transitional evolution? AB - The CEA family consists of two structurally and functionally distinct sub-groups; the group including CEA, NCA and CGM-6 which are cell surface-bound by phosphatidyl-inositol (PI) linkages, and the group of BGP splice variants which have trans-membrane and cytoplasmic domains. Although all CEA family members mediate intercellular adhesion in vitro, the PI-linked group show Ca++ and temperature independent adhesion whereas the BGP group show rapidly reversible Ca++ and temperature dependent adhesion. From the close alignment in cDNA nucleotide sequences between family members and between repeated domains in one family member, it is apparent that the CEA family is now rapidly evolving; in fact, analogs of only the trans-membrane BGP group have been found so far in the mouse. The addition of a new group of potent adhesion molecules to complex species at some time after the rodent radiation has strong evolutional implications, which are discussed. PMID- 1431336 TI - CEA and NCA expressed by colon carcinoma cells affect their interaction with and lysability by activated lymphocytes. AB - Heterogeneous lysability by interleukin-2 activated lymphocytes (LAK) and other immune effectors was observed in the human colon-carcinoma lines LoVo/Dx, LoVo/H and HT29. The tumor cells with high susceptibility to LAK (LoVo/Dx, HT29) expressed higher amounts of the adhesion molecules ICAMl, LFA3 and NCA/CEA than cells with low LAK sensitivity (LoVo/H). Monoclonal antibodies against these molecules caused a marked reduction of lysis by LAK of LoVo/Dx and HT29. A pool of these antibodies induced a nearly complete inhibition of the LAK lysis of both lines. Treatment of LoVo/Dx with differentiating agents (dimethylformamide and retinoic acid) led to a decreased expression of the adhesion molecules, including NCA, accompanied by increased resistance to LAK-mediated lysis. Moreover, the presence of CEA soluble antigen drastically inhibited the cytotoxic activity of LAK effectors against HT29 and LoVo/Dx cells, in a dose-dependent manner. These data indicate that sensitivity of colon-carcinoma cells to activated lymphocytes depends on the level of expression of adhesion molecules, including CEA and NCA. Given the role of CEA-related antigens in tumor/lymphocyte interaction, soluble CEA, frequently released by colon-carcinoma, may be involved in immunosuppressive effects induced in vivo by tumor cells. PMID- 1431337 TI - Immunohistology of carcinoembryonic antigen (CEA). Specificity of reagents, choice of control tissues and practical application in surgical pathology. AB - Immunohistology of CEA has been used now for many years in research and in diagnostic applications. In this congress paper, the need for specificity checks, correct preservation and quality control of antibodies as well as the choice and preservation of control tissues will be discussed and, in addition, some aspects of the interpretation of CEA immunohistology in surgical pathology are illustrated, based upon prospectively collected data from a routine surgical pathology unit. An approach for collection and analysis is demonstrated and the diagnostic importance of CEA expression together with other antigens in the same tumor. PMID- 1431338 TI - External quality assurance of the carcinoembryonic antigen (CEA) assay: main findings in six years' experience. AB - In 1984 we initiated a national external quality assessment (EQA) program (supported by the Italian National Research Council, CNR) for the CEA assay; at present, about 200 Italian laboratories are participating in the program. The laboratories assayed the quality control (QC) samples according to their routine procedures and returned the results together with the name of the method/kit they used. The collected results were computer-processed and reports were sent back to the participants. A significant reduction of the CVt (mean between-laboratory agreement) of the CEA assay was observed throughout the EQA survey (from 35% in 1985 to 20-25% in the last cycles). In order to better clarify the differences in variability observed in the first QC cycles against the last ones, we used the ANOVA technique to evaluate the components of variability. The improvement in between-laboratory agreement was mainly due to the reduction of the between-kit component (from 30.5% to 15.2%), rather than to the smaller decrease observed for the within-kit variability (from 18.4% to 14.0%). The results reported for QC samples from different materials showed differences in the between-lab variability and substantial changes of the kit biases, thus suggesting a different specificity of the antibodies used in the various method/kits against different families of CEA molecules. Considerable uncertainty was also encountered in the clinical classification of low pathological samples, which seems mainly due to the variability in cut-off values used by the laboratories for the clinical assessment of the same analytical results. Our data indicate a progressive increase in the reliability of CEA determination during our study and confirm that EQA has improved the reliability of analysis carried out by the participating laboratories, thus stimulating the kit manufacturers to provide more reliable products. PMID- 1431339 TI - CEA serum levels in non-neoplastic disease. AB - Several non-neoplastic conditions, i.e., acute and chronic inflammations, benign tumors, renal or hepatic insufficiency, are associated with elevated plasma levels of Carcinoembryonic Antigen (CEA). Usually, CEA elevation in these pathologies is less than 10 ng/ml. CEA values in non-malignant disease can be affected by many factors, which can be classified into five main categories: a) tissular, b) physiological, c) metabolic, d) circulating and e) methodological factors. Synthesis, expression and release are the most important tissular factors. Among the metabolic ones liver, biliary and renal functions play a primary role in the determination of CEA concentrations. In addition, other factors such as the presence of circulating CEA-like substances, autoantibodies and immunocomplexes or the characteristics of the assay method can influence the diagnostic value of the CEA test. All these factors must be carefully considered when the marker is used in clinical practice. PMID- 1431340 TI - The role of serum carcinoembryonic antigen (CEA) in the management of patients with colorectal carcinoma: the experience of the Istituto Tumori of Milan. AB - CEA determination has attained an important role in the clinical management of patients with tumors of the colorectal tract. In this paper the experience of the Istituto Tumori of Milan is reviewed and the results are discussed. Three hundred and thirty-six patients were followed after curative resection of colorectal carcinoma. The follow-up period was 15 years, from January 1975 to December 1990 (global follow-up 1358 years). In the course of follow-up 136 patients developed recurrent disease. The number of CEA determinations for each patient ranged from 1 to 37 (mean 8, total 3330). CEA levels of presurgical patients were related to the clinical stage. Among patients who developed recurrences 61% showed an increase in CEA serum levels. In 200 patients with a negative follow-up we observed only 15 cases of false-positive results. PMID- 1431341 TI - CEA determination in the follow-up of extracolorectal neoplasms. AB - CEA was initially described as a tumor and organ specific colorectal antigen, but later found by more sensitive methods in other tumors (stomach, pancreas, lung, breast) and in minor amounts in inflammatory, normal adult and fetal organs of the gastrointestinal tract. The main clinical application of CEA concerns its pretherapeutic and serial determination as circulating antigen in serum and other body fluids by means of CEA-specific, commercially available test kits. By clinical studies a significant correlation has been proven between the pretherapeutic serum CEA level and tumor stages and prognosis. Moreover, serial CEA level changes have been shown a valuable monitor following operation or during radio/chemotherapy anticipating and reflecting the clinical course of disease. In combination with newly established tumor markers, the main clinical indication for CEA determination in addition to colorectal cancer concerns monitoring of patients with stomach (+CA 72-4), lung (+NSE/SCC) and breast cancer (+CA 15-3/MCA). PMID- 1431342 TI - Cost/effectiveness ratio of carcinoembryonic antigen--importance of adequacy of routine requests of tumor markers. AB - Since 1987 we have been evaluating the cost/effectiveness ratio of tumor markers using carcinoembryonic antigen (CEA) as a leading indicator. Preliminary to the evaluation of cost/effectiveness ratio we verified the fitness of CEA requests to the proper clinical problems in order to identify any bias of cost due to inadequate CEA use. 2677 CEA orders were evaluated in 1987. The percentage of inadequate requests was very high (43%). Therefore, it seemed not advisable to carry out the evaluation of cost/effectiveness ratio, while educational actions (divulgation of informative material, service of telephone consultation) were addressed to the physicians of the geographic area of laboratory users. In 1991 the adequacy of CEA requests was reevaluated. The percentage of inadequate requests on 2647 orders was 29.4%. This result, although not yet satisfactory, suggests that proper educational programs may probably improve the fitness of tumor marker requests to correct clinical problems. Additional educational actions are mandatory to further reduce the rate of inadequate tumor marker orders. PMID- 1431343 TI - Cancer imaging with CEA antibodies: historical and current perspectives. AB - This article reviews the history and status of cancer imaging with radiolabeled antibodies against carcinoembryonic antigen (CEA). Although CEA and many other cancer-associated antigens are not distinct for neoplasia, the quantitative increase of these markers in malignant tissues provides a sufficient differential for selective antibody targeting. Animal studies with xenografted human tumors provided the first evidence of the prospects of this technology, followed by initial clinical success with purified goat whole IgG antibodies to CEA, labeled with 131I and with the use of dual-isotope subtraction methods. Subsequently, improved and earlier imaging could be accomplished with monoclonal antibody fragments, which then would permit the use of shorter-lived radionuclides, such as 111In, 123I, and 99mTc. The preferred use of a monoclonal anti-CEA IgG Fab' fragment, labeled with 99mTc by a recently developed, simple and rapid kit, has enabled the detection of small lesions, including those in the liver, within 4 h of injection. By means of SPECT imaging, a high sensitivity and specificity for RAID could be achieved. PMID- 1431344 TI - Pilot, multicenter and prospective trials with an anti-CEA antibody. AB - In this paper we summarize the investigations performed by our group utilizing an anti-CEA monoclonal antibody (F023C5) labelled with different radionuclides in humans. Since 1983 radioimmunoscintigraphy (RIS) was performed on 51 patients with 64 localizations of colo-rectal carcinoma (pilot study). A multicenter clinical trial in a large number of patients (509 pts of which 284 with gastrointestinal cancer) was subsequently carried out in collaboration with ten nuclear medicine centres. High sensitivity and specificity values were obtained by these studies and many unsuspected lesions were recorded. In order to better define the clinical role of RIS, a prospective study was performed on 59 patients with suspected local relapses of colo-rectal cancer. A comparative evaluation of RIS, CT scan, US and MRI was done. RIS and MRI had the highest accuracy (86%) followed by CT scan (68%) and US (54%). PMID- 1431345 TI - Diagnostic applications and therapeutic approaches with different preparations of anti-CEA antibodies. AB - Various preparations of anti-CEA antibodies have shown to detect very sensitively CEA producing tumors. The development of human anti-mouse antibodies (HAMA) prevents from the widespread use of immunoscintigraphy (IS) in the follow-up of patients with colorectal carcinoma. It is, however, not yet clear if genetically reshaped antibodies will solve this problem and it is even less clear if this will change prognosis of these patients. There is certainly room for new therapeutic approaches in colorectal carcinoma. Radioimmunotherapy in combination with other techniques might advantageously complete surgery, chemotherapy and radiotherapy, but needs to be further developed. PMID- 1431346 TI - Anti-CEA and other antibodies in the study of gastrointestinal tumors. AB - Localization of gastrointestinal tumors by means of labeled monoclonal antibodies is a new, sensitive and suitable technique currently used in several centers. Encouraging results have been documented with several monoclonal antibodies by different authors. This article reviews our experience with radioimmunoscintigraphy in 59 patients with colorectal cancer in follow-up, using 131I and 111In labeled B72.3, and in 16 patients with primary gastrointestinal tumors using 99mTc anti-CEA monoclonal antibody (type F023C5). The sensitivity of both B72.3 and anti-CEA was greater than 70% either for primary tumors and abdominal recurrences or distant metastases except hepatic ones. A significant gradient in antibody uptake was measured on surgical biopsies between tumors and normal tissues allowing a good in vivo contrast for gamma detection. We have defined the impact of some factors affecting in vivo tumor targeting. In fact, pharmacodynamics of MAbs, percentage of injected dose bound to tissues were measured, and in particular antigenic content in tumor nodules was quantified. Furthermore, the results of RIS were compared to those obtained by CT and other imaging modalities. PMID- 1431347 TI - Application of genetically-engineered anti-CEA antibodies for potential immunotherapy of colorectal cancer. AB - Hitherto anti-CEA monoclonal antibodies (MAbs), normally of mouse origin, have been used primarily for clinical diagnosis of colorectal cancer, either as a tumor marker in serum to monitor tumor recurrence, or latterly as a means to localize in vivo CEA-bearing tumors, and metastases in patients. In vivo diagnosis using mouse anti-CEA MAbs has so far had limited clinical utility because the antibodies elicit a strong anti-mouse immunoglobulin immune response on repeated administration in man. This problem has been addressed by the development of various strategies for "humanization" of mouse anti-CEA MAbs by genetic manipulation of immunoglobulin genes. Such humanized, engineered antibodies markedly attenuate the antigenic response directed against the MAb, such that safe, repeated administration to patients has become feasible. Such humanized anti-CEA antibodies can thus be radioactively-labelled and applied for in vivo monitoring and detection of recurrent malignant disease, or used for therapeutic strategies which similarly take advantage of the ability of the antibodies to target cytotoxic agents selectively to tumor cells. The application of these novel procedures for manipulating MAb structure presents entirely new opportunities for diagnosis and treatment of human colorectal cancer. PMID- 1431348 TI - Effectiveness of 6-month intermittent administration of natural human interferon alpha against non-A non-B chronic hepatitis. AB - Interferon (IFN) was administered intermittently for 6 months to the patients with non-A non-B chronic hepatitis (CHNANB), and the effectiveness of the treatment for improving the hepatic function was evaluated. Of 26 patients with CHNANB, 16 received intermittent IFN therapy (IFN group), and 10 were treated by conventional therapies without IFN (non-IFN group). All patients were observed for 1 year. IFN was administered once a day at 3 MU in principle (1 MU in some patients and 6 MU in 1 patient) daily for 1 week immediately after the beginning of the therapy and 3 times a week for the subsequent 6 months at the outpatient clinic. The patients were followed up for at least 6 months after completion of the treatment. In the IFN group, the serum GPT level normalized in 11 (68.8%) of the 16 patients 1 year after the beginning of the treatment. In these 11 patients (normalized group), HCV-RNA was negative or became negative in 3 of the 6 patients in whom the serum HCV-RNA could be examined. Histological grades of inflammation in the liver were also markedly alleviated in the normalized group. The hepatic function did not normalize in any of the 10 patients in the non-IFN group. These findings indicate that IFN therapy is useful for CHNANB. PMID- 1431349 TI - [A study of enhancing effects of monocyte culture supernatant on polymorphonuclear neutrophils-chemiluminescence--comparison between normal controls and collagen disease patients]. AB - Priming effect of monocyte culture supernatant on polymorphonuclear neutrophils (PMN)-chemiluminescence (CL) was studied in patients with systemic lupus erythematosus (n = 11) and mixed connective tissue disease (n = 4). In normal controls, N-formyl-methionyl-leucyl-phenylalanine (FMLP) induced PMN-CL was enhanced when PMN were previously incubated for 15 minutes with monocyte culture supernatant (MS) or T lymphocyte culture supernatant (TS) or T lymphocyte culture supernatant (TS). The enhancing effect of MS on PMN-CL was greater than that of TS. This enhancing effect of MS was inhibited by adding of dexamethasone (1 microgram/ml) during the culture. Recombinant human TNF also enhanced PMN-CL as well as MS. When compared the enhancing effects of MS between patients and normal controls, that of patients under corticosteroid therapy (average prednisolone dose 39.5 mg/day) was reduced significantly. Thus, we concluded that the cytokines from monocyte contributed PMN phagocytosis of invading microorganisms, and that this monocyte-mediated PMN phagocytosis was suppressed partly by corticosteroids in collagen disease. PMID- 1431350 TI - [A study of nasal carriage of methicillin-resistant Staphylococcus aureus]. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important microorganisms in nosocomial infection. The Hospital staff working in MRSA endemic wards are known to have MRSA in their nasal cavity. The nasal carriage of MRSA was detected in staff members and patients of two hospitals. In Niigata University Hospital, 10 out of 109 nurses and 8 out of 142 doctors were found to be MRSA carriers. On the other hand, in Nagaoka Red Cross Hospital, 25 out of 448 nurses were found to be MRSA carriers, however, no carrier was found in 23 doctors. These strains were also resistant to MCIPC, IPM, TFLX and OFLX, whereas they remained sensitive to VCM. The coagulase types of MRSA isolated from the hospital staff and patients were II, IV and VII, although those of Methicillin sensitive S. aureus (MSSA) consisted of all types. Elimination of nasal MRSA from the carriers was considered for avoiding hospital outbreaks caused by this potential pathogen. Forty hospital staff and 19 patients, in who's MRSA was found persisting in their nasal cavity, were treated by povidone iodine and chloramphenicol (CP) MRSA disappeared in 44% and 84% of the nasal carriers by povidone iodine and CP, respectively. PMID- 1431352 TI - [Biochemical analysis of lipopolysaccharides from respiratory pathogenic Branhamella catarrhalis strains and the role of anti-LPS antibodies in Branhamella respiratory infections]. AB - We characterized lipopolysaccharides (LPSs) from respiratory pathogenic Branhamella catarrhalis (BC) strains, and evaluated the protective property of anti-BC LPS antibody in BC respiratory infections. LPSs from four strains of BC were lipooligosaccharide having no O-side chain and a M(r) of 3 KDa, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). All of them produced different patterns, showing two to four bands on SDS-PAGE. We found high level of anti-BC IgG antibody in convalescent sera from a patient with BC respiratory tract infection by ELISA. This IgG antibody recognized BC LPSs on Western blots. Two respiratory pathogens of BC (strains; 87-122, 88-23) were tested in a bactericidal assay employing a convalescent sera. 87-122 strain was susceptible to antibody-dependent, complement-mediated killing, while 88-23 strain was resistant. The killing of 87-122 strain was inhibited by addition of the homologous BC LPS to the convalescent sera in a dose-dependent manner. These data support that anti-BC LPS antibody may mediate complement-lysis of some strains of BC, and play a protective role in BC respiratory infections. PMID- 1431351 TI - [Study on lymphocyte-response in early stage of respiratory infection--a view point from experimental Klebsiella pneumoniae pneumonia]. AB - This study was performed to demonstrate the early immuno-responses of lymphocytes in an experimental pneumonia with K. pneumoniae in mature mice (45 week-old) comparing with it in juvenile ones (4 week-old). Acute mice pneumonia was made by inhalation with K. pneumoniae DT-S strains into lung. Changes in lymphocytes including their subpopulation in bronchoalveolar lavage fluid (BALF), peripheral blood, hilar lymphnodes and lung tissue were observed after the inhalation. In addition, lung tissue and hilar lymphnode were examined immunohistologically. The following results were obtained: 1. Total lymphocytes in BALF were more rapidly increased in the mature group than in the juvenile one. But there was no significant change in leukocyte count in peripheral blood between both groups. 2. Such a rapid increase in lymphocytes in BALF in mature group depended on L3T4 Ly6c cells and L3T4-LFA 1 cells. These cells in juvenile group were not accumulated in BALF at initial phase of the infection. But in contrast, they were gradually increased in peripheral blood and in hilar lymphnode. There was significant time-differences in appearance of these cells in BALF between both groups. It might be, that L3T4-Ly6c cells and L3T4-LFA1 cells observed in BALF in mature animals were induced from bronchus-associated lymphoid tissue (BALT) or small lymph tissue in alveolar interstitium, but in juvenile ones were originated in hilar lymphnode. 3. Changes in Ly2-Ly6c cell and Ly2-LFA1 cell were shown the same tendency changes in L3T4-Ly6c cell and L3T4-LFA1 cell. 4. Accumulation of B220:Ly5-LFA1 cell in BALF was not observed in significant difference between the mature group and in the juvenile one. 5. L3T4 cells were markedly accumulation in subcortex area of hilar lymphnode in the juvenile group, but they were only seen scattered in the mature group. 6. It can be concluded that active T lymphocyte begins to response in situ in the early stage of respiratory infection in the mature host and this finding is a characteristic lymphocyte response, that is never seen in the juvenile group. PMID- 1431353 TI - [Antigen detection in the murine models of systemic candidiasis]. AB - We compared two latex agglutination tests for serum candidal antigen in murine models of systemic infection and gastrointestinal colonization. In the intravascular-infection model, mannan detection test was positive at 2 hours after inoculation, but Cand-Tec was less sensitive than mannan detection test in this model. In the gastrointestinal colonization model followed by systemic infection in neutropenic mice, the mannan antigen test became positive after 3 weeks of colonization with increased number of Candida of the stool, and Cand-Tec became positive after 5 weeks in neutropenic mice. PMID- 1431354 TI - [Study on the bacteriological examination of sputum and bronchoscopy specimens from 31 cases with pneumonia due to Chlamydia psittaci]. AB - We carried out the bacteriological examination of sputum and bronchoscopy specimens from 31 cases with pneumonia due to C. psittaci. The results obtained were as follows: 1. The positive culture of sputum and bronchoscopy specimens were 38.7% (12/31). 2. The organisms detected from them were 13 strains of gram negative bacilli, 2 of gram-positive cocci and one gram-positive bacillus. 3. Significant differences were observed in the white blood cell count between the cases of positive culture and those of normal upper respiratory tract flora (p less than 0.05). From the results we conclude that it would be better that we add the proper antimicrobial drugs to chlamydial antibiotics in the treatment of patients with leukocytosis. PMID- 1431355 TI - [Two cases of diffuse panbronchiolitis receiving long-term erythromycin (EM) therapy with acute exacerbation due to EM-resistant pneumococcus]. AB - The first case was a 73-year-old woman with chief complaints of fever, cough, purulent sputum and dyspnea. EM therapy was begun in December 1983 due to a diagnosis of diffuse panbronchiolitis (DPB). Subsequently, P. aeruginosa was persistently detected, while in February 1991 at the time of an acute exacerbation of the DPB P. aeruginosa and S. pneumoniae were detected by TTA. The second case was a 65-year-old man with chief complaints of fever, cough and purulent sputum. DPB was diagnosed and EM therapy was begun in December 1985. In January 1991, pneumonia developed, at the time when S. pneumoniae was detected by TTA. In both cases, rapid disappearance of S. pneumoniae from the sputum and alleviation of symptoms were obtained with carbapenem antibiotic administration. Both strains were resistant to EM, Tetracycline (TC), Minocycline (MINO) and Clindamycin (CLDM). Particularly, S. pneumoniae of case 2 showed low sensitivity to Ampicillin (ABPC), Cefotiam (CTM) and Cefoxitin (CFX) as well. These cases showed acute exacerbations due to EM-resistant pneumococcus during long-term therapy with EM, and are of interest in that they may shed light on the relation between long-term EM therapy and the emergence of resistant pneumococcus. PMID- 1431357 TI - [An outbreak of municipal water-associated food poisoning caused by Salmonella enteritidis]. AB - An outbreak of municipal water-associated food poisoning by Salmonella Enteritidis occurred in Takatoh Town. Nagano prefecture during September 4 to 19, 1989. The major symptoms observed in the 680 patients consisted of diarrhea (70.9%), abdominal pain (51.2%), fever (44.6%), headache (27.9%), nausea (5.9%) and vomiting (5.7%). In the outbreak, S. Enteritidis was the only suspected etiological agent isolated from both patients and municipal water supply. All of the 21 isolates were lysine decarboxylase activity negative. In other respects, the isolates conformed to the general characteristics of Salmonella. All of them were further characterized by phagovar 8 type, uniform drug susceptibilities and carrying 2.7 kb plasmid. Inspite of the evidence that the infection caused by a peculiar strain linked to the strain in municipal water supply used by the patients, it was impossible to determine the exact source of contamination in the water. The outbreak above seems to be the most large-scale among those of Salmonella found poisoning associated with drinking water in Japan. PMID- 1431356 TI - [Epidemiological and bacteriological study on gonococcal infections]. AB - Epidemiological and bacteriological studies on Neisseria gonorrhoeae isolated in Sapporo, Japan, in 1980 and 1991 performed and the following results were obtained. 1. The range of age in the patients infected with Neisseria gonorrhoeae tended to be younger than those in the whole country. 2. Male patients in the early 20s or younger with gonococcal urethritis were often infected by bon professional females but those in their late 20s or older were often infected from professional females, for example prostitutes and hostesses. 3. The rate of professional females who were positive to gonococci reached 17.4% and young females in their teens with cervicitis had the highest morbidity rate of gonococci than those in the older females. 4. The latent period in gonococcal infections tended to become longer gradually. 5. The isolation rate of penicillinase producing Neisseria gonorrhoeae (PPNG) showed a peak of 23.9% (61/255) in 1985, but gradually declined thereafter and it was 3.7% (1/27) in 1991. 6. An investigation on auxotype showed a decline of proto and Pro-strains and an increase of AHU-strains in non-PPNG. And most of the PPNG belonged to proto or Pro-strains. 7. With the relationship between auxotype and sensitivity to AMPC, AHU-strains were more sensitive than proto or Pro-strains. PMID- 1431358 TI - [Food poisoning caused by enteroinvasive Escherichia coli (O164:H-)--a case in which the causative agent was identified]. AB - Food poisoning due to "Godofu (Sasayuki tofu)" as a main causative foodstuff which broke out on July 14, 1988. There were 670 out of 918 persons who ingested this food who became ill (incidence 73.0%). The main symptoms were diarrhea (93.4%), fever (77.5%), abdominal pain (64.5%), and vomiting (19.9%). A high degree of fever and watery diarrhea were characteristic of this poisoning. The average latent period was 35 hours with a range of one to 156. The O164:H- strains of enteroinvasive Escherichia coli (EIEC) were detected from 22 of the 32 fecal samples collected from the patients, five of ten samples collected from workers engaged in tofu making, and one sample of left-over Godofu. The virulence of EIEC strains isolated from the patients, workers, and left-over food was confirmed by invasion into HeLa and HEp-2 cells, Sereny test, and ELISA test to detect invasive plasmid-derived protein of the organism (conducted at Tokyo Metropolitan Research Laboratory of Public Health). These EIEC strains were sensitive (less than or equal to 0.19 to 6.25 micrograms/ml) to GM, ABPC, CBPC, CER, CET, NA, PB, MINO, TC and CP as well as KM and OFLX which were used for treatment. However, their susceptibility to FOM varied to some extent (6.25 to 25.0 micrograms/ml) and one strain isolated from a tofu worker was resistant to MINO, TC, FOM and CP (25 to greater than or equal to 100 micrograms/ml). Since investigation revealed that Godofu was left at room temperature about 29 degrees C until ingested, we did a experiment to check the bacterial growth in Godofu under similar conditions at the time of outbreak.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431359 TI - [Mechanism of acquired resistance against Legionella--blastogenic responses of murine spleen lymphoid cells following the stimulation with Legionella antigens]. AB - We have tried to characterize the blastogenic responses of murine spleen lymphoid cells from BALB/c mice immunized with Legionella pneumophila serogroup (SG) 1 (Philadelphia 1 strain) and non-treated mice. Lymphoid cells from immunized mice showed stronger blastogenic responses following stimulation with concanavalin A or formalin-treated L. pneumophila SG1 whole cell antigen than those showed by lymphoid cells from non-treated mice. These cells from immunized mice also responded strongly when stimulated in vitro with other SGs of L. pneumophila, while these responded weakly when stimulated with other species of Legionella. Serum antibody titers of immunized mice against each SG of L. pneumophila were examined and the cross reactions were also recognized. However, the relatedness of serum antibody titers and the blastogenic responses against each serogroup of L. pneumophila was small. The epitopes recognized by the cellular immunity might be different in part from those recognized by serum antibodies, and investigations should be made on what the cellular immunity recognizes and how it works. PMID- 1431360 TI - Calculus pyonephrosis due to Candida albicans with special reference to serodiagnostic parameters. PMID- 1431361 TI - [Efficacy of levofloxacin on typhoid fever]. PMID- 1431362 TI - [Detection of Chlamydia trachomatis in first-voided urine sediments from male urethritis by polymerase chain reaction]. AB - Chlamydia trachomatis was detected from first-voided urine sediments of 97 male patients with urethritis by polymerase chain reaction (PCR). Since urine and urinary sediments only treated with proteinase K inhibited DNA amplification by PCR, DNA was further purified by phenol extraction and concentrated. Two oligonucleotides based on sequences within the major outer membrane gene from C. trachomatis serovar L2 were used as primers. A DNA fragment of 242 bp specific for C. trachomatis was amplified by PCR and detected by agarose gel electrophoresis. The DNA fragment was amplified by PCR in all specimens of urine sediments from 50 patients with Chlamydiazyme-positive urethral swab. In 38 specimens of urine sediments from 47 patients with Chlamydiazyme-negative urethral swab, PCR was negative. The overall coincidence rate between the PCR for detecting C. trachomatis in first-voided urine sediments and Clamydiazyme in urethral swab was 90.7% (88/97). Detection of C. trachomatis from first-voided urine sediments by PCR was considered to be noninvasive and useful for the diagnosis of male urethritis due to C. trachomatis. PMID- 1431363 TI - [Dose finding study of cefepime for chronic respiratory infections]. AB - In order to determine the optimal dose of cefepime (CFPM) for respiratory tract infections, a dose finding study was conducted in patients with chronic respiratory tract infections, and the clinical properties of the drugs were compared with those of ceftazidime (CAZ). Each drug was administered by intravenous drip infusion at the dose of 2 g/day of CFPM, 4 g/day of CFPM or 2 g/day of CAZ for 14 days. 1. The overall efficacy rates evaluated by the committee were 82.6% (19/23) for the CFPM 2 g/day group, 85.0% (17/20) for the 4 g/day group and 79.3% (23/29) for the CAZ 2 g/day group, with no statistically significant difference among the three groups. 2. The overall efficacy rates evaluated by the attending physicians were 91.3% (21/23) for the CFPM 2 g/day group, 78.9% (15/19) for the CFPM 4 g/day group and 75.9% (22/29) for the CAZ 2 g/day group, with no significant difference among the three groups. 3. Bacteriological eradication rates were 88.2% (15/17) for the CFPM 2 g/day group, 68.8% (11/16) for the CFPM 4 g/day group and 63.2% (12/19) for the CAZ 2 g/day group, with no statistically significant difference among the three groups. 4. The incidences of adverse reactions were 3.8% (1/26) for the CFPM 2 g/day group, 9.1% (2/22) for the CFPM 4 g/day group and 3.4% (1/29) for the CAZ 2 g/day group, with no significant difference among the three groups. The incidences of abnormal laboratory findings were 37.5% (9/24) for the CFPM 2 g/day group, 15.0% (3/20) for the CFPM 4 g/day group and 3.4% (1/29) for the CAZ 2 g/day group. There was a significant difference among the three groups. 5. Utility rates assessed by the committee were 81.8% (18/22) for the CFPM 2 g/day group, 76.2% (16/21) for the CFPM 4 g/day group and 75.9% (22/29) for the CAZ 2 g/day group. Utility rates assessed by attending physicians were 90.9% (20/22), 78.9% (15/19) and 72.4% (21/29), respectively. There was no significant difference among the three groups. From the above results, it is concluded that the optimal dosage of CFPM is 2 g/day for chronic respiratory tract infections. PMID- 1431364 TI - [A comparative study of cefepime for bacterial pneumonia]. AB - The efficacy, safety and usefulness of cefepime (CFPM), a new cephem antibiotic, in bacterial pneumonia, were evaluated in a comparative study against ceftazidime (CAZ). Each drug was administered by intravenous drip infusion at a dose of 1.0 g (nominal potency) twice daily for 14 days, and the following results were obtained. 1. A total of 183 cases were enrolled in this study. Efficacy rates ("good" or better responses) as evaluated by the subcommittee were 90.3% (65/72) in the CFPM group and 94.0% (63/67) in the CAZ group, with no significant difference between the 2 groups. 2. Efficacy rates ("good" or better responses), as evaluated by attending physicians, (in the same bacterial pneumonia cases which were subjected to evaluation by the subcommittee) were 87.5% (63/72) in the CFPM group and 89.6% (60/67) in the CAZ group, with no significant difference between the 2 groups. 3. Bacteriologically, eradication rates were 96.9% (31/32) in the CFPM group and 96.7% (29/30) in the CAZ group with no significant difference between the 2 groups. 4. The incidence of side effects was 5.9% (5/85) in the CFPM group and 4.8% (4/84) in the CAZ group, with no significant difference between the 2 groups. No significant difference was also found between the 2 groups in the incidence of abnormal laboratory findings; 28.4% (23/81) of the case in the CFPM group and 34.1% (28/82) in the CAZ group. 5. As for overall usefulness of the drug in bacterial pneumonia cases, utility rates ("useful" or better evaluations) as evaluated by the subcommittee were 88.9% (64/72) in the CFPM group and 92.5% (62/67) in the CAZ group. The rates as evaluated by investigators (in cases judged as evaluable by the subcommittee) were 87.5% (63/72) and 85.1% (57/67), respectively. There were no significant differences between the 2 groups. These results indicated that CFPM is very useful for the treatment of bacterial pneumonia. PMID- 1431366 TI - [Growth inhibitory activity of clinical isolates of Pseudomonas aeruginosa against Staphylococcus aureus (MRSA and MSSA)]. AB - Anti staphylococcal activity by clinical isolates of Pseudomonas aeruginosa was tested by the reversed agar plate and the filter paper stamp methods. Almost 40% of Pseudomonas aeruginosa inhibited the growth of both Methicillin resistant Staphylococcus aureus (MRSA) and Methicillin sensitive Staphylococcus aureus (MSSA). Green pigment (Pyocyanin) produced strains showed a strong inhibitory effect against MRSA and MSSA respectively. But some other pigment (Yellow, Red) strains also showed anti staphylococcal activity. These data suggest the colonization of Pseudomonas aeruginosa with anti staphylococcal activity may not be eradicated by the anti pseudomonic antibiotics. PMID- 1431365 TI - [A comparative study of cefepime for chronic respiratory tract infections]. AB - The clinical efficacy, safety and usefulness of Cefepime (CFPM), a new cephem antibiotics, in chronic respiratory infections were evaluated in a comparative study against Ceftazidime (CAZ). Each drug was administered by intravenous drip infusion at a dose of 1.0 g (nominal potency), twice daily for 14 days, and the following results were obtained: 1. A total of 170 cases were enrolled in this study. Efficacy rates ("good" or better responses) as evaluated by the subcommittee were 86.2% (56/65) in the CFPM group and 84.5% (60/71) in the CAZ group, with no significant difference between the two groups. 2. Efficacy rates ("good" or better responses) as evaluated by attending physicians were 83.3% (55/66) in the CFPM group and 84.5% (60/71) in the CAZ group with no significant difference between the two groups. 3. Bacteriologically, eradication rates were 83.3% (40/48) in the CFPM group and 88.2% (45/51) in the CAZ group, with no significant difference between the two groups. 4. Side effects occurred in none of the patients in the CAZ group and in 4 of the 66 patients in the CFPM group. There was a significant difference between the two groups (Fisher's test p = 0.0489). The incidence of abnormal laboratory findings were 17.6% (12/68) in the CFPM group and 21.1% (16/76) in the CAZ group. There was no significant difference between the two groups. 5. The utility rates evaluated by the subcommittee were 81.8% (54/66) in the CFPM group and 84.5% (60/71) in the CAZ group with no significant difference between the two groups. Only in the incidence of side effects, there was a significant difference between the two groups (Fisher's test p = 0.0489), but there was no significant difference in other items of efficacy, safety and usefulness between the two groups. These results indicate that CFPM is useful for the treatment of chronic respiratory tract infections. PMID- 1431367 TI - [Effect of gentiana violet against methicillin-resistant Staphylococcus aureus (MRSA)]. AB - The bactericidal effect of gentiana violet against MRSA isolated from clinical specimens was studied both in vitro and in vivo. The results obtained are as follows: 1) Minimum bactericidal concentration (MBC) of gentiana violet to MRSA was between 0.0025% and 0.08% and the MBC was not influenced even if 25% human whole serum exists in the medium. 2) The number of cells were 2.1 x 10(7) CFU/ml in medium which decreased to 5.4 x 10(4) CFU/ml within 5 min by existing 0.1% gentiana violet in the medium as the final concentration, and also decreased under 10(3) CFU/ml 15 min later. 3) Minimum inhibitory concentration (MIC) of gentiana violet to MRSA was between 0.00015% and 0.00063%, and the inhibitory activity was not influenced even if gentiana violet was incubated with the bacteria in the medium for 72 hr at 37 degrees C. 4) By using an ointment containing 0.1% gentiana violet to 12 cases of patients with the MRSA infected skin lesions, MRSA was eliminated completely from the infected areas of the skin within 4 weeks. 5) The side effects of gentiana violet were not observed in all cases during the use of the ointment containing gentiana violet. It is suggested that gentiana violet may be one of the useful drugs for the treatment of the skin lesions infected with MRSA. PMID- 1431368 TI - [Clinical studies on the treatment of Campylobacter enteritis--emergence of quinolone-resistant Campylobacter jejuni after treatment with new quinolones]. AB - In recent years, new quinolones such as ofloxacin (OFLX) and tosufloxacin (TFLX) have been frequently used in the treatment of bacterial enteritis caused by unknown organisms. The agent of first choice for the treatment of Campylobacter enteritis is one of the macrolides, but new quinolones are often administered accidentally to adult patients with Campylobacter enteritis. We have detected quinolone-resistant strains of Campylobacter jejuni (C. jejuni) after the treatment of some patients with new quinolones, and accordingly we reviewed the treatment of Campylobacter enteritis. We experienced 178 adult patients with Campylobacter enteritis from January 1989 to November 1991 at our hospital. From them, we selected 52 patients (32 males and 20 females) in whom stool culture were performed both before and after treatment. The initially administered antimicrobial agent was a macrolide (rokitamycin, RKM) in 6 cases, a new quinolone in 22 cases, and kanamycin (KM) in 24 cases. The new quinolone used was OFLX in 17 cases, TFLX in 3 cases, and norfloxacin (NFLX) in 2 cases. Fifty-one of the 52 C. jejuni strains isolated before treatment were susceptible to OFLX and erythromycin (EM) according to antimicrobial disc susceptibility tests. C. jejuni was eradicated in all patients treated with RKM or KM. However, treatment failed to achieve bacteriological cure in 8/22 (36.4%) patients given new quinolones. In these patients, the strains of C. jejuni isolated before treatment were susceptible to OFLX, but the strains isolated after treatment were all resistant to OFLX according to disc susceptibility tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431369 TI - [Shigella dysenteriae strains having a provisional serovar isolated from imported diarrheal cases in Tokyo]. AB - Two bacterial strains (ME448 and ME474) isolated from stool cultures of imported cases in Tokyo in 1987 had typical biochemical characteristics of Shigella dysenteriae. The results of antigenic analyses showed that they were serologically identical to each other, but did not belong to any of the established Shigella serovars. These strains were positive for Sereny test in guinea pig eye and cell-invasion test in HeLa cells. The strains also had virulence-plasmid encoding outer membrane proteins, indicating that they were pathogenic. We then contacted the Centers for Disease Control in the United States and the Central Public Health Laboratory in the United Kingdom and arranged serological examinations of the strain ME448. From the results, the strain was confirmed to have provisional S. dysenteriae serovar E23507. Although the serovar had been isolated from a Swedish patient who developed diarrhea while in India, this is thought to be the first report of its isolation in Japan. PMID- 1431370 TI - [Clinical study of eradicated and resistant patients to treatment with ivermectin for strongyloidiasis]. AB - We treated 70 patients with strongyloidiasis (41 males and 29 females) with ivermectin (IVM), and obtained the following results: 1. The eradication rates at 1-2 months, 3-4 months and 5-6 months after treatment were 90.7% (49 of 54 patients), 100.0% (47 of 47 patients) and 95.7% (45 of 47 patients), responsively. Twelve patients were resistant (non-responsive) to treatment. 2. When compared to patients whose parasites were completely eradicated, the resistant patients showed the following results: 1) Incidence of symptoms observed before treatment was significantly lower (50.0% vs. 84.5%). 2) Positive rate of anti-HTLV-I antibody was significantly higher (66.7% vs. 20.7%). 3) Blood eosinophil counts before treatment were significantly lower (266.6 +/- 117.2/mm3 vs. 533.2 +/- 429.7/mm3). 4) Serum IgE levels before treatment were significantly lower (217.2 +/- 442.9 IU/ml vs. 1,076.8 +/- 2,108.0 IU/ml). 5) There were no significant differences in age, sex and dosage of ivermectin. 3. Comparing anti HTLV-I antibody positive and negative patients, the following results were obtained: 1) Eradicated patients; a) Eosinophils and IgE levels before and after the first administration of medicine in anti-HTLV-I antibody positive patients were significantly lower than those of negative patients. b) Gammaglobulin levels before treatment and after both administrations of the drug, IgG before therapy and OKT4/OKT8 after therapy were significantly higher than in anti-HTLV-I antibody positive patients. 2) Resistant patients; Eosinophils after treatment were significantly lower in anti-HTLV-I antibody negative patients than in positive patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431371 TI - [Rapid diagnosis of influenza infection by PCR method--detection of influenza virus HA gene in throat swab]. AB - We studied the detection of the HA gene of human influenza viruses in throat swabs obtained from the outbreaks of influenza in school children utilizing the polymerase chain reaction (PCR) method. Sensitivity and specificity of the PCR method was compared to conventional virus isolation using MDCK cells. Three pairs of primers for PCR in detecting the HA genes of AH1, AH3, and B influenza viruses showed both subtype and type specificity. The dilution experiments showed that influenza viruses, as few as 1.1-3.5 plaque-forming units per 50 microliters, were sufficient for the detection of HA genes by PCR method and the detection rate by PCR method was 2-3 fold higher than that by conventional method. Our results showed that the PCR method was a fast, sensitive and reliable method for the diagnosis of influenza infections. PMID- 1431372 TI - [Isolation of vero-cytotoxin-producing Escherichia coli from cattle and serotyping and toxin-typing of the isolated strains]. AB - Two hundred and sixty-six piglets with diarrhea (from 4 farms), 73 healthy pregnant pig (from 2 farms), 27 calves with diarrhea (from 9 farms) and 47 healthy milk cows (from 1 farm) were examined for Vero-cytotoxin-producing Escherichia coli (VTEC), and 52, 11, 15 and 67 strains of VTEC were isolated from 17 piglets, 11 pregnant pigs, 6 calves and 23 milk cows, respectively. All VTEC strains from the piglets produced only VT2vp, while the strains from the healthy pigs did not produce VT2vp, but did VT1 and/or VT2. Most VTEC strains from calves and cows produced VT2vhb and some produced VT2 and VT1. Serotyping of the isolated strains showed that many strains from the piglets belonged either O139:H1, O141:H4 or O141:HUT, but the strains from the pigs were either R-form or O-untypable. Many strains from the calves and cows were serotyped into O116 or O113, but there were several R-form and O-untypable. From these results, it is suggested that VTEC strains, especially from the pregnant pigs, calves with diarrhea and healthy milk cows, which produced the same type of Verotoxins to that produced by human isolates, may become sources of human infections. PMID- 1431373 TI - [Dynamic process of colonization by Haemophilus influenzae in children--is H. influenzae normal flora in the throat?]. AB - Eighty-seven oropharyngeal isolates of Haemophilus influenzae were obtained by two time cultures six months apart from a total of 288 children who attend a kindergarten. We analyzed the strains by comparing their serotypes, biotypes, beta-lactamase activity and by performing electrophoresis of outer membrane proteins on polyacrylamide gels. Only nineteen strains were not identical, the rest of the 68 strains were classified into 23 types. During 6 months at least 15 types of strains lost from this group and 21 types of new strains were obtained. There were no children who had identical pairs of H. influenzae in their oropharynx during the 6 months. The classification of strains in oropharynx suggested that person-to-person transmission of nontypable H. influenzae can occur. We concluded that oropharyngeal colonization by nontypable H. influenzae is not a normal flora in children. PMID- 1431374 TI - [Study on local immune response in Escherichia coli-induced experimental urinary tract infection in mice--infiltration of Ia-positive cells, macrophages, neutrophils, T cells and B cells]. AB - We studied the local immune response in a mouse experiment with acute ascending cystitis and pyelonephritis. The experimental infections were induced in BALB/c female mice by transurethral instillation of Escherichia coli O6. Immune response cells were stained, including Ia-positive cells, macrophages, neutrophils, T cells (CD4+ and CD8+) and B cells (IgA, IgM, IgG-positive B cell). They were stained by the immunohistochemical method (ABC method) using monoclonal antibodies against lineage specific antigens except for neutrophils that were readily identified by the standard hematoxylin-eosin. Even in the control mice having no evidence of the infection, mucosa associated lymphoid tissue (MALT) consisted of macrophages, Ia-positive cells and T cells that were sparingly found in the urinary tract tissue and renal parenchyma. Ia-positive cells, macrophages, neutrophils, T cells (CD4+, CD8+) and IgA positive B cells were significantly infiltrated in the bladder submucosa from 6 hours after bacterial inoculation. The infiltration of similar immune response cells was found in the submucosa of the renal pelvis, except for IgA positive B cells that appeared one day after the induction of the infection. In renal parenchyma, Ia-positive cells appeared at 6 hours after introduction of the infection, followed by an infiltration of neutrophils, macrophages and T cells (CD4+, CD8+) at the first day, and IgA positive B cells at the third day. These results are summarized as follows. When microbes invaded the urinary tract tissue, a significant number of Ia-positive cells infiltrated, which were initially present in normal urinary tract tissue. Subsequently, neutrophils, macrophages and T cells (CD4+, CD8+) appeared in the lesion followed by a delayed occurrence of IgA positive B cells. PMID- 1431375 TI - Chlamydial epididymitis diagnosed by genetic detection of Chlamydia trachomatis from epididymal aspirate by polymerase chain reaction. PMID- 1431376 TI - [A case of pneumonia due to Mycoplasma pneumoniae accompanying high adenosine deaminase activity in pleural effusion]. AB - We experienced a 5-year-old male case of Mycoplasma pneumoniae pneumonia accompanying Adenosine Deaminase (ADA) activity in pleural effusion. Chest roentgenograms revealed the infiltration in the left upper lung field and the left pleural effusion. In serum, the M. pneumoniae CF titer increased to 1:512. The pleural effusion was yellowish in color, with a specific gravity of 1.030, protein 3.7 g/dl, glucose 101 g/dl, and ADA 50 IU/l. Pleural effusion accompanying M. pneumoniae pneumonia is rare, and the high ADA activity in this case has been reported only in one other case. This is a report of a high activity of ADA in the pleural fluid by M. pneumoniae pneumonia. PMID- 1431377 TI - [A case of eosinophilic meningitis due to Angiostrongylus cantonensis]. AB - We report a case of eosinophilic meningitis caused by Angiostrongylus cantonensis. This patient, a 50-year-old male, had been eating uncooked slugs for 40 years. His chief complaints on admission were headache, fever and general fatigue. Neurological examination and CT findings were normal, but the CSF contained increased cells, most of which were eosinophilic cells. The presence of eosinophilic cells in the CSF is by itself abnormal. We therefore suspected eosinophilic meningitis and performed immunological tests. Since the gelatin particle method and immunological antigen antibody reaction were positive. We diagnosed the patient as having eosinophilic meningitis caused by Angiostrongylus cantonensis. There are only 27 reported cases of this disease in Japan, and most of them have been reported in Okinawa-Prefecture. PMID- 1431378 TI - [Detection of Neisseria gonorrhoeae in first-voided urine sediments from male urethritis patients by polymerase chain reaction]. AB - Neisseria gonorrhoeae was detected from first-voided urine sediments of male patients with urethritis by polymerase chain reaction (PCR). Urine and urinary sediment were treated with proteinase K, and DNA was further purified by phenol extraction. Two oligonucleotides based on sequences within a ribosomal RNA gene from N. gonorrhoeae were used as primers for the PCR. A DNA fragment of 206 bp specific for N. gonorrhoeae was amplified by PCR and detected by agarose gel electrophoresis. In 19 specimens of urine sediments collected from 21 patients in whom N. gonorrhoeae was isolated from urethral swab by culture, 206 bp DNA fragment was amplified by PCR. In all specimens of urine sediments from 24 patients in whom cultures for N. gonorrhoeae were negative, no DNA was amplified by the PCR. The overall coincidence rate between the PCR for detecting N. gonorrhoeae in first-voided urine sediments and culture in urethral swab was 95.6% (43/45). PCR procedure for detection of pathogens from first-voided urine sediments would be noninvasive and would be applied for the diagnosis of gonococcal urethritis and chlamydial urethritis. PMID- 1431379 TI - A clinical study on patients with urinary tract infection due to coagulase negative staphylococci. AB - To assess the clinical significance of coagulase-negative staphylococci (CNS) in patients with urinary tract infection (UTI), the clinical characteristics of a total of 117 patients (106 complicated UTI patients, 11 uncomplicated UTI patients) from whom CNS were isolated at urinary colony counts of 10(5) or more per ml were studied. Of the complicated UTI patients, 95 patients (89.6%) suffered from no symptoms while 11 (10.4%) had fever of 38 degrees C or greater, which was strongly suspected to be due to genitourinary tract infections. Six of these patients were managed by indwelling urinary catheters. On the other hand, all of the patients with uncomplicated UTI were young women and had typical symptoms of acute cystitis. These results suggest that CNS, which hitherto have been considered mere contaminants or benign colonization rather than true pathogens, can also cause complicated UTI requiring chemotherapy under certain conditions such as indwelling urinary catheterization and acute cystitis in sexually active women. PMID- 1431380 TI - [Vectors of Japanese spotted fever]. AB - In the southeast coast of Shikoku, most of the Japanese spotted fever (JSF) patients were found to be infected with the rickettsial pathogen through bamboo plantation, and also the eschar was frequently noticed in skin inspection, so that it was clinically speculated to be caused by ticks. According to out field research, the tick fauna was very rich throughout that area, and it was permissible enough to determine ticks as the vectors, based on arising of anti-SF group rickettsiae (SFGR) antibody in mice inoculated with some tick emulsions, findings of rickettsiae reactive to patient sera or a species-specific monoclonal antibody to JSFR in the hemolymph cells of some ticks, and electron microscopical observations of SFGR in various internal organs including the salivary gland of ticks. Also the transovarial and transstadial transmission of SFGR in ticks were supposed. Our results suggest that common species (adult/nymph) of the genus Haemaphysalis may be the most related vectors to man, based on their dominances, SFGR-prevalences, behavior and incidences of infestation but also indicate that various genera and species should be kept as the potential vectors, in spite of JSFR isolation from a restricted species of ticks in the future. PMID- 1431381 TI - [Detection of hepatitis delta virus (HDV) markers in HBV carriers]. AB - To investigate the prevalence and clinical features of hepatitis delta virus (HDV) superinfection in hepatitis B virus (HBV) carriers, antibody to hepatitis delta antigen (anti-HD) was determined in the sera of 328 HBV carriers in Japan. 1) Of the 328 HBV carriers, six (1.8%) were seropositive for anti-HD by enzyme linked immunosorbent assay. IgM-antibody to hepatitis delta antigen was detected in 2/6 patients with a high anti-HDV titer. None of the patients was positive for hepatitis dealt antigen. 2) HBV carriers with chronic liver disease had a greater frequency of seropositivity of anti-HD than asymptomatic HBV carriers. These data indicate that HDV superinfection may be an etiologic agent of chronic liver disease in HBV carriers. PMID- 1431382 TI - [Clinical study of albendazole therapy for strongyloidiasis]. AB - We reported the efficacy of albendazole (ABZ) for the treatment of 27 patients with strongyloidiasis. Twenty-seven patients, 23 males and 4 females, received 200 mg of ABZ one hour before breakfast and supper for 3 days and this treatment was repeated 2 weeks later. The following results were obtained: 1) The eradication rate at 2 weeks after the initial treatment was 70.4% (19 of 27 patients) and 2 weeks after the second course was 66.7% (16 of 24 patients). 2) One patients (3.7%) complained of abdominal pain after the first treatment. Four patients (14.8%) complained of headache (n = 2), nausea (n = 1) and exanthema (n = 1) after the second treatment. But all symptoms were mild and required no treatment and subsided in a few days. 3) Positive rate of HTLV-1 antibody was 45.8% in the patients. As described above, side effects occurred in some cases, although they were mild and transient. From these results, it can be concluded that on increased dose of ABZ could be much more favorable for the treatment of strongyloidiasis. PMID- 1431383 TI - Drug resistant plasmid of Actinobacillus pleuropneumoniae isolated from swine pleuropneumonia in Thailand. AB - Actinobacillus pleuropneumoniae, isolated from the pneumonic lung tissue of pigs, was resistant to streptomycin, sulfadiazine and tetracycline. This isolate, TA5, possessed 2 plasmids (pTA51 = 3.7 Kb, pTA52 = 6.2 Kb); one of the plasmids (pTA52) was coded for resistance to SM and SA. Another isolate of A. pleuropneumoniae, TA8, also possessed 2 plasmids (pTA81 = 3.7 Kb, pTA82 = 4.4 Kb), with a plasmid (pTA82) coded for resistance to SM and SA. All 4 plasmids were not transmissible and small. PMID- 1431385 TI - [A survey of intestinal parasites of the foreign laborers (Indonesians and Filipinos) in Ishikawa Prefecture]. AB - A survey of intestinal parasites was conducted on 198 foreign workers aged 19-27 from Inodonesia and Philippines. They work for a private company in Ishikawa Prefecture as technical trainee. On the base of stool examination, 94 (71%) out of 133 Indonesians and 48 (74%) of 65 Filipinos had intestinal helminths and/or protozoan infections. The prevalence of Ascaris lumbricoides, Trichuris trichura and Hookworm was 4.5, 64.1, 10.6%, respectively. In addition, the positive rate of the cyst of Entamoeba coli, Endolimax nana, Blastocystis hominis and Giardia lumblia was 11.1, 5.6, 4.5 and 2.0%, respectively. No E. histolytica was found; however, counter current immunoelectrophoresis revealed that one out of 112 sera possessed the antibody against the antigen of HK-9 strain of E. histolytica. Sixty-three cases of trichuriasis were treated with mebendazole at a dose of 200 mg/day x 3 consecutive days. Re-examination revealed that 53 (85.5%) of them were cured. PMID- 1431384 TI - [An epidemiological study on Bordetella pertussis infection in Fukui Prefecture from 1986 to 1991--especially observation on the patients of culture-confirmed pertussis]. AB - In order to clarify the epidemiological situation of whooping cough in Fukui prefecture, 478 nasopharyngeal swabs from patients with pertussis-like symptoms were submitted to bacterial isolation. Laboratory data of these patients with clinical informations at the departments of pediatrics of 6 hospitals in Fukui city from June 1986 to May 1991 were also examined in relation to the above bacterial isolation. The results observed in culture positive patients were as follows: 1) B. pertussis were isolated from 83 patients (41 men and 42 women). 2) Isolates were classified into 3 serotypes. Most dominant type was 1.3.6 (80 strains, 96.4%), and followed by 1 (2 strains) and 1.4.5 (1 strain). 3) Most of the patients were non-vaccinees less than 3 years of age (69 of 83 (83.1%). This evidence suggested strongly that pertussis vaccine was highly effective to prevent pertussis. 4) The patients under 3 years of age whose leucocyte counts were > or = 15000/mm3 and lymphocyte rate to total leucocyte were > or = 70% in their peripheral blood at the time of nasopharyngeal swabs sampling were only 49.3% (33 of 67). Therefore, diagnosis of pertussis by leucocyte findings alone were considered to be inadequate. 5) The area of the patient's residence covered 7 regions of 8 health center districts in Fukui prefecture. The areal distribution of the number of patients from June 1986 to May 1991 was relatively proportional to the population of each district.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431386 TI - [Studies on tsutsugamushi diseases in Gifu Prefecture. 5. Characterization of monoclonal antibodies to prototype strains of Rickettsia tsutsugamushi and immunological grouping of newly isolated strains using the antibodies]. AB - We characterized 8 monoclonal antibodies (MAbs) to Karp, Kato, and Gilliam strains of Rickettsia tsutsugamushi, and analysed 17 isolates from patients with Tsutsugamushi disease using these MAbs. These were divided into 3 strain-specific (Kp/D11, Kt/2D9, and Gi/E4) and 5 cross-reactive MAbs (Kp/1F11, Kp/1C10, Kp/C6, Kt/3B2, and Kt/3C2). All MAbs recognized characteristic protein antigens using the indirect fluorescent-antibody test (IFA) and proteinase K treatment. Analysis by polyacrylamide gel electrophoresis and immunoblotting techniques revealed that Kato-specific MAb Kt/2D9 recognized a polypeptide with a molecular mass of 54 kilodalton (kDa) of the homologous strain, and cross-reactive MAbs Kp/1F11, Kp/C6, and Kt/3B2 recognized those of 46-47 kDa, 46-47 KDa, and 60 kDa, respectively to the homologous and heterologous strains. MAbs Kp/1C10 which exhibited a high IFA titer against the Karp strain and only low titers against heterologous strains recognized only the 110 kDa polypeptide of the homologous strain. MAb Kt/3C2 which reacted with both Karp and Kato strains recognized a 54 to 56 kDa polypeptide band of the two prototype strains as well as several other polypeptides, however, each molecular mass was present in only one of two strains. Testing by the plaque reduction technique showed another characteristic of MAb Kt/3C2 to neutralize both Karp and Kato Strains. Fourteen isolated strains from patients in the south and west regions of Gifu Prefecture, the Shimokoshi stain isolated in Niigata Prefecture, and Kawasaki and Kuroki stains isolated in Miyazaki Prefecture were examined for reactivities to 8 MAbs by IFA to classify their antigenicities. No isolated strains reacted with Karp-specific Kp/D11, Kato specific Kt/2D9, or Gilliam-specific Gi/E4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431387 TI - Drug-resistant Staphylococcus aureus contamination in the ward environment. AB - A total of 282 strains of Staphylococcus were isolated from University Hospital ward environment from April 1991 to January 1992 and drug-susceptibility tests were performed. The main isolates were 84 strains of S. epidermidis (30%), 65 strains of S. aureus (23%), and 58 strains of S. haemolyticus (21%). One hundred and thirty-six strains of all staphylococci (48%) and 13 of 65 strains of S. aureus (20%) were methicillin (DMPPC)-resistant. The DMPPC-resistant strains of S. aureus were multiple drug-resistant to three to seven antibiotics; ampicillin. cephaloridine, cephametazole, tetracycline, erythromycin, gentamicin, and methicillin, while the DMPPC-susceptible strains were resistant to less than two drugs. These results indicate that this routine testing, along with testing of the anterior nares of the medical staff, is necessary to prevent nosocomial transmission. PMID- 1431388 TI - [Etiology of pneumonia and host defense]. AB - To investigate the relationship of efficacy of chemotherapy to host defense, we reviewed the clinical features, treatment and outcome in 648 patients with acute pneumonia (424 males and 224 females; mean age, 65 years) treated between 1984 and 1989. Pneumonia complicated pulmonary disease in 336 patients (52%) and complicated systemic disease in 258 (40%). Pneumonia pathogens were diagnosed in 346 patients (53%); the five major pathogens were S. pneumoniae (19%), H. influenzae (16%), S. aureus (14%), K. pneumoniae (14%) and P. aeruginosa (11%). The incidence of K. pneumoniae infection were decreased from 18% to 3.5% and that of S. aureus increased from 10.9% to 26.3% during the study period. The incidence of S. aureus and of P. aeruginosa infection was much higher in patients with nosocomial pneumonia, systemic disease, or serum protein concentration under 6.5 g/dl. beta-lactamase antibiotics were administered to 70% of all patients, with an efficacy rate of 74.9% of after the first course of antibiotics therapy. The efficacy rate was decreased in patients with nosocomial pneumonia, systemic or pulmonary disease, or malnutrition. The data presented in this study indicate that the risk of pneumonia must be taken into careful consideration in patients with compromising complications. PMID- 1431390 TI - [A case of miliary tuberculosis presenting as fever and jaundice with hepatic failure looking like the course of fulminant hepatitis]. AB - A 79-year-old male was admitted to the Metropolitan Hiroo Hospital with chief complaints of icterus and fever. A few weeks prior to admission, he developed fever and swelling of right side of the neck and was seen at a local hospital where an anti-inflammatory agent was prescribed. The fever subsided in a few days, but recurred together with development of icterus a few weeks later, precipitating this hospitalization. After admission, hepatic failure progressed rapidly, indicating a fulminant hepatitis. Renal failure also developed and he died. Autopsy revealed diffuse caseous necrosis with demonstration of acid-fast bacilli in the liver, as did in the spleen, kidney and bone marrow. This case epitomizes a subset of miliary tuberculosis in which the hepatic failure predominates the clinical presentation while lacking the ante-mortem chest X-ray features suggestive of pulmonary tuberculosis and post-mortem macroscopic changes indicative of tuberculosis. PMID- 1431389 TI - [Clinical evaluation of SD-8828 (antibody coated bacteria assay kit) in urinary tract infection]. AB - Clinical usefulness of a newly developed assay kit for ACB (SD-8828) which detects urinary bacteria coating IgG was evaluated and compared to the enzyme antibody plate method. A total of 48 patients including 20 patients with acute simple cystitis and 28 patients with acute or chronic pyelonephritis, who were shown to have pyuria of at least 5 cells/HPF, bacteriuria of at least 10(4) CFU/ml were enrolled in this study. By enzyme antibody method. ABC was positive in 92.9% of patients with upper urinary tract infection and negative in 100% of patients with lower UTI, this difference being statistically significant (p < 0.02). By SD-8828, 85% of positive coincidence rate and 100% of negative coincidence rate, compared to the enzyme antibody technique, was obtained. The overall coincidence rate was high (91.7%). This SD-8828, a new simple assay for ACB, which detects IgG alternating the plate method, may be used as a convenient method in clinical practice. PMID- 1431391 TI - [Dynamics of neutrophils in the gastric mucous layer of Helicobacter pylori associated chronic gastritis]. PMID- 1431392 TI - [Treatment of typhoid fever with tosufloxacin]. PMID- 1431393 TI - Ethics in dentistry. AB - In this article I would like to do two things: to discuss the foundations of ethical thinking in general, and to link this discussion to the particular concern of dentists. My argument is divided in three sections: Firstly, I shall attempt to define the term 'ethics' and briefly outline the context for the discussion of professional ethics. Secondly, I would like to draw attention to the categories and approaches in ethical thinking and also to the complexity of any adequate ethical reflection. In my third and final section I shall try to make a few suggestions in terms of how dentists could incorporate ethical thinking in their understanding of the dental profession. PMID- 1431394 TI - Tooth coloured inlays: state of the art. PMID- 1431395 TI - Late developing odontome in the lower premolar area--the enigmatic variations. PMID- 1431396 TI - The oral care of HIV positive patients at Berlin clinic. AB - Two final year dental students spent an elective period in the HIV clinic of the Dental Hospital of the Freie University of Berlin. The oral manifestations and management of 50 HIV patients were observed. PMID- 1431397 TI - Three years postgraduate programme in orthodontics: final report Erasmus project. AB - A new curriculum with a common content of 75%, leaving 25% for electives has been developed for a three year programme for specialty education in Orthodontics. The result is a joint effort of the original eight participants and invited professors from Italy and Eire as well as from five non-EC countries (Austria, Finland, Norway, Sweden and Switzerland). Unaminity among the 15 participants was reached on all essential matters and on the contents of the final report. The main objective of the programme has been defined and the different courses have been formulated in terms of goals to be accomplished in three levels of comprehension and by the minimal hours students must devote to each subject. Furthermore, procedures that should be mastered have been specified. PMID- 1431398 TI - [Mitral valve surgery for patients after undergoing percutaneous transvenous mitral commissurotomy (PTMC)--investigation on indication of PTMC based on the intraoperative findings]. AB - Ten patients underwent open heart surgery for mitral valve after PTMC because of post PTMC MS (n = 4) and MR (n = 6) out of 150 patients undergoing PTMC in our hospital between June 1987 and October 1991. Intraoperative findings of 4 patients with residual mitral stenosis included severe thickening, stiffening and calcification on anterior and posterior leaflets, commissures and subvalvular apparatus. Mitral valve repair was possible in 2 and mitral valve replacement (MVR) was necessary in the other 2. In all 6 cases who massive mitral regurgitation after PTMC, in repairable tears in the mitral leaflets necessitated MVR. Since in these cases changes in the leaflets were less severe than those of the commissures or subvalvular apparatus, surgical repair could have been possible if open mitral commissurotomy (OMC) was done primarily. Patients selection for PTMC versus OMC based on precise morphological evaluation of mitral valve would reduce occurrence of massive MR resulting in surgical replacement. PMID- 1431399 TI - [Left ventricular performance after patch reconstruction of the left ventricular wall for postinfarction left ventricular aneurysms]. AB - Left ventricular performance in patients with a left ventricular aneurysm (LVA) treated with patch reconstruction is largely unknown. This study consisted of 15 patients, 14 men and 1 woman, with the average age of 59 +/- 8.5 years. The resected area of LVA was 40 +/- 27 cm2. The area of the woven Dacron patch used for reconstruction was 57 +/- 19% of the resected area including the sewing rim. The EF (Ejection Fraction, 1/3FF (Filling Fraction) and PFR (Peak Filling Rate) were calculated by 99mTc equilibrium cardiac pool scintigraphic images. The A/R ratio (peak velocity during atrial kick phase/peak velocity during the rapid filling phase) was measured using Doppler echocardiography, at the mitral orifice level. These parameters were determined before and 1 to 2 months after the operation. The time course was followed for A/R ratios. The preoperative resting global EF was 0.28 +/- 0.14 (0.44 +/- 0.13 for the contractile area) and the EF during exercise was 0.31 +/- 0.14. Resting and exercise EFs improved significantly (p < 0.01) to 0.40 +/- 0.11 and 0.43 +/- 0.10 postoperatively. The 1/3FF (%) and PFR (/sec) were low before operation (1/3FF, 11.3 +/- 8.3; PFR, 1.2 +/- 0.47). Postoperatively, the 1/3FF rose to 14.8 +/- 9.3 and the PFR showed a significant (p < 0.05) increase to 1.6 +/- 0.6. The A/R ratio significantly (p < 0.05) improved from preoperative 1.76 +/- 0.46 to 0.95 +/- 0.11 on the 3rd postoperative day. This improvement was maintained until the late postoperative period, with a value of 1.14 +/- 0.29 at month 16.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431400 TI - [Effects of open-heart surgery on renal function in patients with chronic renal failure--is hemodialysis during cardiopulmonary bypass really required?]. AB - In 300 consecutive adult patients who underwent open-heart surgery in our department, 16 patients (ischemic heart disease in 8 patients, valvular heart disease in 7 and congenital heart disease in 1) were preoperatively complicated with chronic renal failure (CRF); creatinine clearance (Ccr) < 40 ml/min and serum creatinine (Scr) > 1.6 mg/dl. The effects of open-heart surgery on renal function were studied in these CRF patients who were divided into the following 3 groups according to their preoperative Ccr values: Group 1 (6 patients), 30 < Ccr < 40 ml/min; Group 2 (5 patients), 20 < Ccr < 30 ml/min; and Group 3 (5 patients, 4 of whom were on dialysis preoperatively), Ccr < 10 ml/min. In addition, Group C (38 patients, Ccr > 50 ml/min) was set up as normal controls. Instead of hemodialysis, the extracorporeal ultrafiltration method (ECUM) was employed for all patients during the cardiopulmonary bypass (CPB). The Ccr in Group 1 showed the lowest value of 24.2 +/- 12.0 ml/min on postoperative day (POD) 0 which then recovered to the preoperative level on POD 1. This quick recovery of the Ccr in Group 1 was similar to that in Group C. In contrast, the Ccr in Group 2 showed the lowest value of 13.0 +/- 6.0 ml/min on POD 1, followed by a delayed recovery that did not reach the preoperative level until POD 5. The Ccr in Group 3 was quite low (< 5 ml/min) throughout the test period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431401 TI - [Surgical treatment of primary cardiac tumors]. AB - Twenty patients with primary cardiac tumors were operated on during the past ten years. The age of 15 female and 5 male patients ranged from 17 to 73 years. Eighteen patients had myxomas, 16 of which located in the left atrium and 2 in the right atrium. Systemic embolism occurred in 8 patients, subsequently caused cerebral infarction in 4, ischemia of extremities in 2, myocardial infarction in 1 and pulmonary infarction in 1. Emergency operation was performed in 5 patients because of severe congestive heart failure. In all cases, removal of myxoma was performed together with the excision of the wall to which the pedicle attached with the use of cardiopulmonary bypass. One patient with pulmonary infarction underwent resection of the infarcted lung simultaneously. Only one patient with severe heart failure died of pulmonary insufficiency one month after the operation. Another patient with cerebral infarction underwent clipping of cerebral aneurysm which appeared later in the infarcted area. The 17 patients including the latter patient showed a good recovery and no local recurrence during the follow-up period of 1 to 120 months. Two patients had malignant tumors, which were malignant fibrous histiocytoma of the left atrium and leiomyosarcoma of the pulmonary artery, respectively. Both of these rare tumors were resected noncuratively and led to the death because of their local recurrence with distant metastasis, though they received adjuvant chemotherapy. The symptoms, complications, diagnoses, surgical treatment and outcome of the primary cardiac tumors are reviewed in this study. PMID- 1431402 TI - [The effects of protease inhibitor upon the ischemia-reperfusion injury]. AB - The purpose of the study is to investigate the effects of protease inhibitor (Nafamostat mesilate: NM) upon myocardial protection. Hearts were subjected to 20 min working control perfusion followed by 3 min cardioplegic infusion with the St. Thomas Cardioplegic Solution (ST) contained various concentrations of NM, and global ischemia for 33 min at 37 degrees C (Exp. 1) or 150 min at 20 degrees C (Exp. 2). Hearts were then converted to Langendorff reperfusion (the leakage of Creatine Kinase (CK) and Cathepsin B (Cat-B) ware measured) and 20 min working reperfusion. Various concentrations of NM added during Langendorff reperfusion (Exp. 3). During working perfusion cardiac functions (aortic flow (AoF), coronary flow (CoF), heart rate (HR), aortic pressure (AoP)) were measured, and expressed as the percent recovery of pre-ischemic control value. Post-ischemic recovery of AoF (%AoF) showed the bell-shaped dose-response curve, and the optimal dose was 3 microM (Exp. 1) and 10 microM (Exp. 2) respectively. There was a significant (p < 0.05) increase of %AoF in optimal dose compared with that in controls (64.2 +/- 1.2% vs 52.3 +/- 2.5% in Exp. 1, 68.9 +/- 3.1% vs 54.1 +/- 1.4% in Exp. 2). These increase of functional recovery reflected in the values for CK and Cat-B leakage. The addition of NM in ST reduced CK and Cat-B leakage significantly in the concentration of 5 microM (in Exp. 1) and 10 microM (in Exp. 2) respectively. But the addition of NM in reperfusate did not reduced CK leakage significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431403 TI - [Late postoperative outcome of plastic operation versus valve replacement for mitral regurgitation]. AB - Between January 1980 and August 1991, 99 patients underwent operation for mitral valve regurgitation (MR). The ages of the patients ranged from 12 to 67 years, (49.4 +/- 11.9 years), and there were 39 males and 60 females. Pathological cause of regurgitation, which was determined by intraoperative inspection and histological findings of excised leaflets, was rheumatic in 46, degenerative in 38, infective endocarditis in 9, ischemic in 4 and unknown in 2 patients. Cardiac rhythm was atrial fibrillation in 73, normal sinus rhythm in 24 and junctional rhythm in 2 patients. Our principles for valve repair were (1) excision of responsible segment and repair for prolapsed leaflet due to torn chordae, (2) shortening of elongated chordae, (3) annuloplasty, and (4) repair of perforated leaflet. Finally, 19 patients endured plastic operation, and 80 patients underwent prosthetic valve replacement. The rate of plastic procedure was 62.5% (10/16) in degenerative MR with mural chordal lesions, 42.9% (3/7) in rheumatic MR without stenosis, 22.2% (2/9) in infective endocarditis and 100% (2/2) in MR with unknown etiology. Mitral valve repair was failed both in rheumatic MR associated with stenosis (39 patients) and in ischemic MR (4 patients). A ten year survival rate after operation was 92.2 +/- 3.1% in patients with valve replacement and 83.6 +/- 10.0% with valve repair (N.S.), and a proportion of event-free survival in patients with valve replacement was similar to valve. Late postoperative cardiac catheterization revealed decreased left ventricular volume indices and increased left ventricular end-systolic stress/volume ratio in both groups compared to preoperative values, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431404 TI - [The evaluation of pre and intraoperative factors influencing the false lumen after graft replacement surgery to the extended dissecting aneurysm]. AB - We evaluated the residual false lumen of type I and IIIb dissecting aneurysm by CT, MRI and angiography postoperatively. The 19 patients with type I dissecting aneurysm were included eleven men and eight women, the average age was 55.8 +/- 10.2 years old. The 20 patients with type IIIb dissecting aneurysm were included sixteen men and four women, the average age was 56.2 +/- 8.5 years old. The rate of distal patent false lumen was 52.6% of type I and 35% of type IIIb dissecting aneurysm after graft replacement surgery. In type I dissecting aneurysm, the rate of distal patent false lumen was 40% of acute stage vs 66.7% of chronic stage, 66.7% of ascending and partial arch replacement vs 46.2% of ascending and total arch replacement, and 90% of graft inclusion technique vs 11.1% of graft exclusion technique. The distal patent false lumen was the lowest (12.5%) with type I dissecting aneurysm of ascending and total arch replacement using graft exclusion technique. In type IIIb dissecting aneurysm, the rate of patent false lumen was 66.7% of acute stage vs 29.4% of chronic stage, 30% of graft exclusion technique vs 40% of graft inclusion technique. The size of false lumen preoperatively were larger (11.1 +/- 4.5 cm2) in patients with distal patent false lumen than that (6.7 +/- 3.2 cm2) of in patients with distal occlusive false lumen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431405 TI - [Coronary artery bypass surgery in patients with severely impaired left ventricular function]. AB - The efficacy and problem of coronary artery bypass grafting (CABG) in patients with severely impaired left ventricular function (left ventricular ejection fraction < or = 30%) were assessed in 27 patients of whom 17 (group 1) underwent emergent CABG and 10 (group 2) elective between Jan 1984 to Aug 1990. As a whole, history of myocardial infarction (24/27, 88.9%), large left ventricular volume with reduced ejection fraction (LVEDVI 126.08 +/- 25.91 ml/m2, LVESVI 93.04 +/- 21.02 ml/m2, LVEF 25.04 +/- 4.75%) and multiple vessel disease with at least one vessel total occlusion (20/27, 74.1%) were characteristically seen in these patients. The patients of group 1 were significantly older (mean 66.12 +/- 5.68 vs 57.10 +/- 8.08, p < 0.01) and needed more frequent preoperative support with IABP (17/17 vs 4/10, p < 0.01). Using Thallium-201 scintigraphy, in 10 patients of group 1 and 9 of group 2, myocardial viability in the proposed bypass area was evaluated before operations. Average 2.37 +/- 0.79 grafts were placed and continuous retrograde cold blood cardioplegia via the coronary sinus was employed for myocardial protection. Two mitral annuloplasty (MAP) for ischemic mitral regurgitation and 2 cryoablation for the treatment of ventricular tachycardia were performed concomitantly. Operative mortality was 47.1% in group 1 and none in group 2 (p < 0.05). Two cases of MAP died, but two cases of cryoablation survived. Postoperative LVEF was improved significantly only in group 2 (p < 0.05), but during the follow-up period of 7 months to 6 years, all 19 survivors expect one remains with NYHA class I or II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431406 TI - [Results of surgical repair by muscle flap closure for poststernotomy mediastinitis]. AB - Between 1984 and 1991, 30 patients developed poststernotomy mediastinitis after cardiac or mediastinal operations. Sixteen of these patients were treated with debridement and open drainage or primary closure following mediastinal irrigation (drainage group). Fourteen patients were treated with debridement, and delayed or primary wound closure by the technique of pectoral or rectus abdominus muscle flap mobilization (muscle flap group). The purpose of this study was to compare the results of the different treatment of poststernotomy mediastinitis. Although the pre- and perioperative profile, complications and risk factors for mediastinal infection were the same, the mortality of muscle flap group was significantly lower than that of drainage group (Fisher exact probability test, p < 0.05). Pulmonary function of the patients who received muscle flap mobilization did not decrease from the function before surgery, despite the defect of sternal bony stabilization. We conclude that muscle flap mobilization may be a superior method as the treatment for poststernotomy mediastinitis after cardiac operations, and may not decrease respiratory function of the patients. PMID- 1431407 TI - [A case of thymoma with thymic cyst]. AB - A 43-year-old man was pointed out an abnormal shadow on chest X-ray film. Chest CT showed a solid mass and a cyst at anterior superior mediastinum. Operation revealed a capsulated thymoma and a multilocular thymic cyst. PTH and CA19-9 level in the cystic fluid was elevated. Histological examination demonstrated the clear separation of the mixed type thymoma and the thymic cyst. There were few reports for cases of thymoma with a thymic cyst. PMID- 1431408 TI - [A case of pulmonary rupture with primary pulmonary leiomyosarcoma--management by emergency surgical intervention]. AB - We report a case of 18-year-old boy who was admitted to our hospital for hemoptysis and hemothorax caused by rupture in the pulmonary tissue. A tumoral mass was found protruding from the inferior aspect of the left lower lobe towards the diaphragma. A large hematoma was seen in the vicinity of the tumoral mass. An emergency left lower lobectomy was performed and the hematoma was removed. The tumor was yellow in color, soft and 7 cm in diameter. The histological diagnosis was that of primary pulmonary leiomyosarcoma. The resected lobe had a liver-like hard consistency due to extended infiltration of blood resulting from hemorrhages within the tissue located in and around the tumoral mass. Microscopically, the tumor was composed of the spindle-shaped cells with multinucleation along with some clear cell patterns. Recurrence of the tumor appeared six months after the operation, and a second resection of the recurrent leiomyosarcomatous tissue was performed. The patient is still alive for 1 year and 6 months after the first operation. PMID- 1431409 TI - [Acute aortic dissection in a patient with Marfan's syndrome and severe pectus excavatum--emergency surgical repairs of ascending aortic dissection and aortic regurgitation complicated by pectus excavatum in Marfan's syndrome]. AB - A case of acute aortic dissection Stanford Type A occurring in a patient with Marfan's syndrome, complicated with aortic regurgitation and severe pectus excavatum, is reported with successful surgical correction. The patient was a 33 year-old woman, who suffered from severe back pain riding to work. An emergency operation consisting of Cabrol's procedure for aortic dissection Stanford Type A and sternal turnover for pectus excavatum was performed simultaneously. Because of the postoperative mediastinal bleeding the implanted sterno-costal complex was removed on the second POD and the prosthetic sternum was reimplanted on the tenth POD. The two-stage operation seems preferable in such an emergency case to avoid postoperative bleeding and infection. PMID- 1431410 TI - [Clinical experience of a percutaneous ventricular support for profound heart failure following acute myocardial infarction--a case report]. AB - Percutaneous biventricular support with centrifugal pump was applied to a 59-year old man with profound heart failure following acute myocardial infarction. Direct coronary angioplasty was performed under percutaneous cardiopulmonary support (PCPS). After angioplasty, he could not be weaned from PCPS under IABP. We used percutaneous left ventricular support (PLVS) with transseptal left atrial cannulation. PLVS could not maintain effective assist flow and he developed a cardiogenic shock again. PCPS was added to PLVS, and percutaneous biventricular support was started. Assist flow ranged 1.7-3.0 L/min in PLVS, and 1.7-2.0 L/min in PCPS, and total assist flow was 3.4 L/min. Pulsatile pressure was obtained by adding IABP. The patient was successfully weaned from PCPS in 26 hours and PLVS in 118 hours. Patient is alive and well one year after PLVS. Combination of PLVS and PCPS is an effective ventricular support system, being less invasive than conventional method with thoracotomy, and may be useful for profound heart failure. PMID- 1431411 TI - [Coronary artery bypass surgery in a patient with hypopituitarism]. AB - Patients with hypopituitarism are prone to perioperative complications resulting from adrenal insufficiency or hypothyroidism. Coronary artery bypass grafting was performed safely in a 53-year-old woman with postinfarction unstable angina and hypopituitarism. Cortisol and thyroid hormone were administered to maintain normal adrenal and thyroid function during and after the operation. Hydrocortisone was administered intravenously the day before surgery and for 2 weeks postoperatively and then was administered orally. Perioperative replacement thyroxine therapy was administered to avoid acute myocardial ischemia. Optimal thyroid replacement was achieved after surgery. No perioperative complications were seen. The patient remains free of angina with postoperative cortisol and thyroid hormone replacement therapy. PMID- 1431412 TI - [A case of complete circumferential aortic rupture due to blunt chest trauma]. AB - A case of complete circumferential rupture of the thoracic aorta due to blunt chest trauma is presented. A 46-year-old woman was admitted after a traffic accident. The admission chest X-ray film demonstrated rib fractures and mediastinal widening. CT scanning and aortography were performed, but acute rupture of the aorta was not detected. Twelve days later, aortography was performed again and an aneurysm was noted at the aortic isthmus. Surgery was performed immediately and aorta was found to be completely disrupted for a length of 1 cm. A short segmental prosthesis was interposed between the two ends of the aorta under temporary bypass. Patients with aortic rupture due to blunt chest trauma are increasing, but only a few cases treated in the acute stage have been reported. To our knowledge, this is the 6th case of complete aortic disruption which has been treated successfully in the acute stage in Japan. PMID- 1431413 TI - [Development of constrictive pericarditis 20 years after closed mitral commissurotomy--a case report]. AB - Pericardial constriction has emerged as an infrequent but well documented late complication of cardiac surgery. A rare case of constrictive pericarditis developed 20 years after closed mitral commissurotomy was observed. The patient had been treated for the poorly controlled ascites of unknown origin associated with crural edema and mild congestive liver cirrhosis. The long interval between the previous cardiac operation and the clinical manifestation of constriction made it difficult to establish the diagnosis. Extensive resection of the calcified pericardium through a median sternotomy with cardiopulmonary bypass standby relieved the ascites and crural edema. PMID- 1431414 TI - [A case of ascending aortic dissection after aortic valve replacement in congenital bicuspid aortic valve]. AB - Congenital bicuspid aortic valve is a risk factor of aortic dissection, but the case is rare in Japan. Several reports described ascending aortic aneurysm after aortic valve replacement. In these reports, most of aneurysms were false aneurysm, but the cases of ascending aortic dissection were rare. In this case, dissecting aneurysm of the ascending aorta occurred 4 years after aortic valve replacement, which was performed with mechanical prosthesis because of infective endocarditis, and it was repaired successfully by the modified Cabrol's method. This case was congenital bicuspid aortic valve, and had already been complicated with moderate aortic dilatation in the ascending aorta. In patients of congenital bicuspid aortic valve with aortic dilatation, consideration of complete replacement of the ascending aorta with aortic valve replacement is important. PMID- 1431415 TI - [Recurrent thymic carcinoid tumor--report of a case and review of the literature]. AB - A case is presented of a 48-year-old male patient with thymic carcinoid tumor who was operated on twice and followed for 12 years. The original tumor was removed in 1979, and a recurrent tumor was removed 4 years later. Multiple metastases to the lungs, pleura and lymph nodes of the neck were found in 1988; chemotherapy (BAPP) and radiation therapy were not effective, and there was subsequent subcutaneous invasion of the anterior chest. We also discuss the 153 cases of thymic carcinoid tumor reported in the Japanese literature in the Niigata Carcinoid Registry. PMID- 1431416 TI - [A case of aortitis syndrome treated by simultaneous procedure of Bentall's operation and aortic arch replacement]. AB - The case is a 22-year-old man, in whom chest X-P pointed out aortic and cardiac shadow enlargements. Aortography revealed extensive aortic aneurysm involving the ascending, arch, and proximal descending portions of the aorta, accompanied with annulo-aortic ectasia, aortic regurgitation, and stenosis of the left common carotid and left subclavian arteries, suggesting lesions due to aortitis syndrome. For this case, Bentall's operation and replacement of the aortic arch and the proximal descending aorta were performed simultaneously, using hypothermic selective cerebral perfusion. Favorable postoperative course and absent neurological abnormality enabled the patient to return to his former social work. Steroid therapy has been continued up to the present, 5 years postoperatively, with neither recurrence of inflammation nor occurrence of cardiac murmur. PMID- 1431417 TI - [A successful operative case of congenital mitral stenosis associated with double outlet right ventricle, patent ductus arteriosus, persistent left superior vena cava and severe pulmonary hypertension in adult]. AB - A 29-year-old woman, who was diagnosed as congenital mitral stenosis associated with DORV, PDA, PLSVC and severe pulmonary hypertension, was reported. The mitral valve, consisting of leaflet dysplasia, shortened and thickened chordae tendineae, obliteration of interchordal spaces, under-development of papillary muscle, and stenotic supravalvular membrane, was replaced with 25 SJM prosthesis. Simultaneously, patch closure of VSD and intrapulmonary direct closure of PDA was performed. Her postoperative course was uneventful and systolic pulmonary arterial pressure fell down from 95 mmHg to 56 mmHg. She is doing well after correction. To our knowledge, this is very rare corrective case with congenital mitral stenosis in adult to be reported in the literature in Japan. PMID- 1431418 TI - [Cellular schwannoma of the lung]. AB - A case of cellular schwannoma of the lung in 31 years-old Japanese male is presented in this paper. Cellular schwannoma differs from classic schwannoma in several histologic features. In addition, it has often been misdiagnosed as malignancy, though White's follow-up study confirmed its benign nature. It usually originates from the retroperitoneum and posterior mediastinum. No case originating from the lung has been reported in the world literature. Cellular schwannoma has to be added to differential diagnosis of the lung tumors. PMID- 1431419 TI - [Thymic carcinoid tumor--report of 3 operative cases]. AB - Three cases of thymic carcinoid were surgically treated in our hospital. All 3 cases belonged to stage IVb (Masaoka's classification) because of anterior lymph nodes metastasis. A 44-year-old male patient died of multiple metastasis of bone and liver in 94 months after the operation. A 45-year-old female patient who had undergone operation 4 years ago, was re-operated on for recurrent carcinoid tumor but complete resection of the tumor could not be performed because of the tumorous invasion to superior vena cava, pericardium and costal bone. After the operation she has been treated by radiotherapy and any re-growth of the tumor has never been detected for 1 year. Another 50-year-old male patient who had been operated and treated by chemo-radiotherapy for thymic carcinoid before 50 months was diagnosed as recurrent tumor at left interpectoral lymph node. Radiotherapy is now preparing for this patient. 160 cases of thymic carcinoid reports in Japan were reviewed. 37 cases were stage IVb and 36 cases had supraclavicular or mediastinal lymph nodes metastasis. Those cases which had been underwent complete resection followed by radiotherapy seemed to have better prognosis. We conclude that patients of thymic carcinoid should be treated with complete resection including supraclavicular and mediastinal lymph nodes dissection, followed by radiotherapy. PMID- 1431420 TI - Alcohol can inhibit effect of IL-4 on activated murine B cells. AB - Ethanol addition to B lymphocytes in vitro inhibits antigen-induced antibody secretion and antigen-induced cell proliferation. We tested the hypothesis that ethanol can inhibit the effect of interleukins on B-cell proliferation by adding ethanol to in vitro functional assays for IL-2 and IL-4. Ethanol does not inhibit IL-2-induced B-cell differentiation, but it does inhibit IL-4-induced B-cell proliferation and IL-4-induced Ig class switching. PMID- 1431421 TI - Major histocompatibility complex-linked transport proteins and antigen processing. AB - The major histocompatibility complexes of mice, rats and humans each contain a pair of related genes, Tap-1 and Tap-2, that encode members of a large superfamily of proteins having similar structure and function. The TAP-1 (previously called HAM1 in the mouse) and TAP-2 (HAM2) proteins each contain 6-8 predicted membrane-spanning alpha helices, and a cytoplasmic domain containing a putative ATP-binding site. Recent evidence suggests that a functional TAP-1/TAP-2 heterodimer is required for efficient presentation of antigens to CD8+ cytotoxic T cells. This heterodimer resides in the membrane of the endoplasmic reticulum (ER), and probably functions to transport peptides (produced in the cytoplasm) into the ER lumen for binding to MHC class I molecules. PMID- 1431422 TI - Histocompatibility antigens and natural killer susceptibility. AB - The central question of the nature of the structure(s) involved in the recognition of targets by natural killer (NK) cells remains unresolved. Although NK-mediated cytotoxicity is not MHC-restricted, it has been suggested that these cells could recognize the targets more effectively in the absence of MHC class I antigens. In this paper we review the contradictory results obtained when studying the NK susceptibility of cell lines which constitutively express different levels of MHC antigens, or which have been induced to express MHC antigens by gene transfection or gamma-interferon treatment. Taken together, the results indicate that MHC antigens play a differential role in NK lysis depending on the nature of the target cells used; MHC class I antigens play a role in the NK resistance of cells from a hematopoietic lineage, but this does not extend to cells from other origins. The data reviewed also support the hypothesis that MHC class I antigens induced NK resistance by interfering with target structures, and that multiple NK molecules are involved in NK-mediated lysis as part of a possible advanced recognition system. PMID- 1431423 TI - Ocular tissue involvement in HIV infection: immunological and pathological aspects. AB - The CNS afflictions in AIDS are myriad and suggest a tropism of HIV to neural tissue. Ocular involvement is a frequent manifestation of the HIV infection, resulting in a high incidence of blindness within this patient population. Ocular lesions include cotton wool spots, presumably from HIV-induced microvasculopathy, retinal hemorrhage in cytomegalovirus retinitis and conjunctival Kaposi's sarcoma. These manifestations have been noted in up to 71% of AIDS patients. In fact, ocular disease is often the presenting symptom in an HIV-infected individual. Despite the high incidence of ocular involvement in AIDS patients, the etiology and pathogenesis of these manifestations are not well understood. The immunosuppressive action of HIV is the most likely primary cause for the development of ocular complications in AIDS. Here we review some of the important immunological and pathological features of AIDS affliction in the eye. PMID- 1431425 TI - IgG autoantibodies to C1q do not detectably influence complement activation in vivo and in vitro in systemic lupus erythematosus. AB - The influence of IgG antibodies to C1q (C1qAb) on activation of the classical pathway of the complement system was investigated in patients with systemic lupus erythematosus (SLE). In in vivo experiments, a prototype for immune complexes was administered intravenously to 14 patients and 9 healthy controls. Eight SLE patients had increased C1qAb titers. The increase of C3a levels, which was measured as a parameter of C1 activation, was significantly lower in SLE patients than in the healthy controls (p = 0.01). No correlation was found between C3a increases and C1qAb titers. In in vitro experiments the influence on C1 activation of monomeric IgG isolated from serum of 11 SLE patients, 7 of whom had increased C1qAb titers, was measured in a C4 consumption assay. The presence of C1qAb did not influence C4 consumption. The results demonstrate that C1qAb do not influence C1 activation by immune complexes in SLE patients. PMID- 1431426 TI - Complement profile in primary biliary cirrhosis. AB - PBC is a chronic progressive liver disease of unknown etiology. Several abnormalities found in PBC support the hypothesis that it may be considered an autoimmune disease. Despite the complex and interesting relationship that exists between autoimmune disorders and the complement system, very few reports on the level of the serum complement component in PBC have been published, and most of these comprised only a few patients or analyzed only a scant number of the complement components. In the present study, sera of 73 PBC patients were analyzed for the levels of 10 complement components. It was found that the levels of most of the serum complement components, including C1q, C2, C3, C5, C7, properdin and factor B were significantly elevated in patients with PBC in comparison to healthy controls. The level of C4 was slightly lower than that of the normal controls (p = 0.019), while the levels of C6 and C8 were within the normal range. The number of PBC patients with serum levels of C4 and C6 < 60% of normal pooled serum was higher than in the respective control groups (6/69 compared with 0/26 and 4/71 compared with 0/27, respectively). However, the difference was not statistically significant. Thus, our study shows alterations in the levels of most complement components in PBC, the reasons for which are discussed. PMID- 1431424 TI - Effects of polyunsaturated fatty acids on interleukin-2-dependent T cell growth. AB - Cellular membranes, in addition to serving as structural constituents of cells, also provide precursors for a number of chemical messengers involved in intracellular signal transduction. This includes the eicosanoids (prostaglandins and leukotrienes) and diacylglycerol, and activator of protein kinase C (PKC). Changes induced in the fatty acid profile of lymphocytes can influence vital metabolic processes in cells. Such changes, independent of the function of fatty acids as prostaglandin and leukotriene precursors, can alter the development and regulation of immune responses. In this report we study the effects of the polyunsaturated fatty acids (PUFA) on proliferation and signal transduction in the interleukin-2 (IL-2)-dependent murine T cell line CTL.L-2. Culture of CTL.L-2 cells in the presence of specific PUFA resulted in their incorporation into the cellular phospholipids. IL-2-induced proliferation of CTL.L-2 cells was markedly suppressed in a dose-dependent fashion by incubation in media supplemented with dihomogammalinolenic acid (an n-6 PUFA) slightly inhibited proliferation, while eicosapentaenoic acid (an n-3 PUFA) had no effect. Neither indomethacin (a cyclooxygenase inhibitor) nor nordihydroguaiaretic acid (NDGA, a lipoxygenase inhibitor) reversed the effect of DGLA. In contrast, phorbol 12-myristate 13 acetate (a phorbol ester and activator of PKC), blocked, in a dose-dependent manner, the antiproliferative effect of DGLA. This study presents evidence that PUFA alter signal transduction in cells in a manner which is separate from their function as eicosanoid precursors. The botanical lipid-derived DGLA has a potent suppressive effect on IL-2-driven T cell proliferation and may alter signal transduction by modification of second messenger or PKC activity. PMID- 1431427 TI - An unexpected growth pattern: considerations in management. AB - A case study spanning 16 years is presented. Routine treatment with serial extraction and an edgewise appliance for a Class I crowded occlusion began when the patient was 8 years old. By the time the patient was 17, his dentition had evolved, because of unanticipated growth, into a Class III malocclusion with complete-arch crossbite. The question of whether it is most appropriate to treat this patient in one or two surgical procedures is discussed, and some controversial aspects and concerns are presented. PMID- 1431428 TI - Lingual nerve injury associated with superior border wire fixation. AB - The sagittal ramus osteotomy of the mandible is the most frequently performed orthognathic surgical procedure. Stabilization of the osteotomy may be accomplished by rigid internal or wire fixation. This article illustrates lingual nerve injury following a bilateral sagittal ramus osteotomy of the mandible and fixation with a superior border wire. The etiology and surgical management of this injury are described. PMID- 1431429 TI - The Dentofacial Deformity Program of the University of Michigan: organization, analysis of data, and benefits of program. AB - The Dentofacial Deformity Program of the University of Michigan was established in 1984 to provide a consulting service for the diagnosis, treatment recommendations, and management of patients with dentofacial deformities. This program was designed as a service commitment for the patient, referring doctors, and the medical and dental communities. Educational and research aspects of the program provide benefits for orthodontic and oral and maxillofacial surgery graduate students, and the dental school faculty. The organization, data analysis, and education, research, and service benefits of this program are discussed. PMID- 1431431 TI - Simultaneous orthognathic and temporomandibular joint surgery: review of selected cases. AB - The pros and cons of, and treatment considerations for, simultaneous orthognathic and temporomandibular joint surgery are discussed. Several cases of patients treated with simultaneous orthognathic and temporomandibular joint surgery are presented. PMID- 1431430 TI - Surgical-orthodontic correction of mandibular deficiency: five-year follow-up. AB - Changes in dental and skeletal relationships at 5 years postsurgery were evaluated in a group of 35 patients whose mandibular deficiency had been corrected by the same surgeon, using sagittal split osteotomy of the mandibular ramus. From 1 to 5 years postsurgery, there was a small (0.9-mm) but statistically significant mean decrease in mandibular length (condylion to point B). In six patients, the decrease in mandibular length was 2 to 4 mm, and in two it was more than 4 mm, but only one of these individuals had more than a 2-mm increase in overjet. There was no mean change in overjet, but three patients had a 2 to 4-mm increase. Of these, one had 3.2 mm shortening of the mandible, one had 1.4 mm shortening of the mandible, and one had no change in mandibular length but repositioning of the incisors. Most patients had a deep overbite initially, and there was a tendency for the bite to deepen between the first and fifth years postoperatively, more as a result of extrusion of incisors than of mandibular rotation. Remodeling of the gonial angle area, with vertical and/or horizontal repositioning of gonion, was noted in more than half the subjects. It appears that morphologic changes related to continued skeletal remodeling, often compensated for by small changes in mandibular posture or tooth positions, continue after 1 year postsurgery for many patients. PMID- 1431432 TI - Densitometric evaluation of changes in the soft tissue of the chin and the lower lip during the treatment of Class III malocclusion. AB - The aim of this study was to use densitometry of lateral skull teleradiographs to evaluate the changes that occurred in the lower lip and chin after orthodontic or orthodontic-surgical treatment of Class III malocclusion. Forty teleradiographs from 20 patients with mandibular prognathism were made at the beginning and end of treatment. In ten of these patients the treatment was exclusively orthodontic with an edgewise appliance, and in another ten the treatment was orthodontic with a straight wire appliance combined with orthognathic and mentoplastic surgery. In the patients who were only treated orthodontically, a significant increase in density of the lower lip and the chin was found after treatment. This seemed to be related to an increase of muscular tension in these areas. Patients treated with orthognathic surgery and the straight wire appliance showed a decrease in density of the chin after treatment, but not of the lip. This can be interpreted as a consequence of muscular normalization after this procedure was accomplished. PMID- 1431433 TI - The reliability of computerized cephalometric soft tissue prediction following bimaxillary anterior subapical osteotomy. AB - The accuracy of predicting the results of orthodontic-surgical treatment following bimaxillary anterior subapical setback osteotomy was analyzed retrospectively. Comparisons of pretreatment prediction tracings of the lateral cephalograms with the 6-month postsurgical cephalograms of 38 patients showed that there was no statistically significant difference between the actual and predicted dentoalveolar setback in both arches. The computer-generated soft tissue predictions were generally accurate, with the exception of the horizontal position of the lower lip, which was underestimated, and, to a lesser extent, the vertical position of the upper lip, which was also underestimated. Computerized cephalometric prediction following bimaxillary anterior subapical osteotomy is sufficiently accurate to be of value to be used routinely in treatment planning for the horizontal upper lip prediction, but some modifications are advisable to obtain a more accurate horizontal lower lip prediction. PMID- 1431435 TI - [Analysis of DNA synthetic cells in endometrial carcinoma cases treated with progestogen]. AB - It is well known that the proliferation of endometrial adenocarcinoma is inhibited by progestogens. We often use medroxyprogesterone acetate (MPA) as endocrine therapy for advanced endometrial carcinoma. In the present study, we administered 400-600mg of MPA/day on 14 days as a progestogen challenge test (PCT) to 37 cases of endometrial carcinoma. We analysed the variation in the percentage of S phase cells by flow cytometry and also conducted an immunohistochemistry analysis with anti-BrdU monoclonal antibody before and after the administration of MPA. The percentage of S phase cells in endometrial carcinoma tended to decrease with much greater variation after PCT than before. The percentage of BrdU positive cells tended to decrease after PCT. The cases with a good histological effect such as 1) basal vacuolization 2) clear staining cytoplasm 3) homogenus finding of cells and nucleus by PCT had a better prognosis than the cases with no histological effect due to PCT. PMID- 1431434 TI - [In vitro study on the effect of sex steroid and growth factor on growth and laminin, collagen IV, and tissue plasminogen activator production of normal endometrial cells and endometrial cancer cells in culture]. AB - The mechanism of the invasion and proliferation of endometrial cancer is closely related to interactions between the endometrial glands and stroma. In this study, we examined the biological role of sex steroids (estradiol; E2, progesterone; P) and growth factors (epidermal growth factor; EGF, transforming growth factor beta; TGF-beta) on cell growth and laminin, collagen IV and tissue plasminogen activator (t-PA) production of normal endometrial cells and endometrial cancer cells in culture. Normal endometrial gland cells and stromal cells, and endometrial cancer cell lines (Ishikawa, OMC-2) were used. E2, P, EGF and TGF beta were added to the culture in physiological concentrations. The growth of normal endometrial gland cells was promoted by E2 and EGF, whereas that of Ishikawa cells and OMC-2 cells was promoted by EGF. E2 enhanced the effects of EGF in normal endometrial gland cells. The growth of normal endometrial stromal cells was not affected by them. OMC-2 was inhibited by anti-EGF receptor antibody. On the other hand, the production of laminin and collagen IV of these cultured cells was inhibited by EGF and promoted by TGF-beta, whereas that of t PA was promoted by EGF and inhibited by TGF-beta. These results suggest that the growth of normal endometrial gland cells with estrogen receptor (ER) is controlled by both E2 and EGF, whereas that of endometrial cancer cells is affected only by EGF, and those cells without ER depend particularly on the autocrine growth mechanism of EGF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431436 TI - [Assessment of pre-term uterine contractions by characterization of the power spectra of abdominal surface potentials (ASP)]. AB - The prognosis of pre-term labor in the absence of complications such as PROM is dependent on the strength of the uterine contractions, which are dependent on the sensitivity of the myometrium, expressed in terms of bio-electric potentials. Our electromyography were obtained from pregnant ewes, and these were correlated with abdominal surface potentials (ASP) obtained from human volunteers, to see if impending premature labor could be detected and the prognosis predicted. 1) The EMG tracings obtained from pregnant ewes were submitted to a power spectrum analysis. 2) EMG tracings revealed an increase in power output with the advance of labor, but power spectra varied with the stage of labor. 3) Uterine contractions not leading to cervical ripening had a low power output with a low frequency range. 4) Ewes in true labor had EMG's at a high power output of low frequency waves. 5) Ewes in pre-term labor leading to cervical ripening had power outputs similar to ewes in true labor, but the power spectra of the former were wider in range. 6) ASP tracing revealed an increasing power output with increasing uterine contractile activity and power spectra correlated well with the EMGs obtained from ewes. In conclusion, since ASP findings were in good correlation with EMGs obtained directly from the myometrium, we hope that this method may be developed into a practical non-invasive method for detecting and assessing uterine contractions. PMID- 1431437 TI - [Analysis of HLA antigens and immunotherapy for infertile couples who failed to conceive after in vitro fertilization-embryo tubal replacement (IVF-ETR)]. AB - The results of IVF-ETR strongly suggest the existence of implantation failure of unknown etiology. A selected group of 41 couples with long-standing infertility who had one or more failed IVF-ETR cycles were analysed for HLA antigen sharing, and 19 wives were immunized with their husband's purified lymphocytes just before the subsequent trial. Both the number and frequency of shared HLA antigens in these patients were significantly increased, compared with control couples of normal fertility (p < 0.05). After immunization, 7 patients (36.8%) conceived by IVF-ETR, and 5 (71.4%) delivered a healthy baby at term. The pregnant couples shared significantly fewer HLA antigens compared with those who failed to conserve (p < 0.05). Interestingly, the MLR blocking effect was enhanced in the pregnant group after immunization, suggesting the induction of blocking antibodies which are believed essential for the survival of the developing fetus. In contrast, the blocking effect was rather decreased in the nonpregnant group. These results implicate that HLA sharing and inadequate maternal anti-paternal immunity may be related to implantation failure, and immunotherapy can be used to potentiate the maternal immune response, leading to successful implantation in selected patients. PMID- 1431438 TI - [Influence of low calcium diet on the vascular response to angiotensin II in pregnant and non-pregnant rabbit vascular endothelium]. AB - This study was conducted in order to evaluate the influence of low calcium intake on the vascular response to angiotensin II (A-II) in pregnant and non-pregnant rabbits. Both were fed on a regular and a low calcium diet, respectively, for a period of at least 25 days. By using the common iliac arterial rings of each of the rabbits, and further classifying the respective arterial rings into those with intact endothelium and those with denuded endothelium, the response to A-II in the rings was compared. A greater degree of refractoriness to A-II was observed in the intact endothelial rings than in the denuded rings regardless of the difference in calcium intake, in both pregnant and non-pregnant rabbits. The refractoriness was however, particularly remarkable in the pregnant arterial rings. Therefore refractoriness to A-II in arterial rings on a low calcium diet is higher than that in the rings on a regular calcium diet regardless of the presence of endothelial cells, in both pregnant and non-pregnant rabbits. It is clear that reduction in the calcium intake results in an increase in the response to A-II, which is caused by increased reactivity of the vascular smooth muscle layer. PMID- 1431439 TI - [Effect of gonadotropin releasing hormone agonist (Gn-RHa) on steroidogenesis in human and rat ovaries]. AB - The effects of Gn-RHa on rat granulosa cells and on human granulosa and luteal cells were examined. (I) In rat granulosa cells: 1) Gn-RHa inhibited the stimulating effect of PMSG on progesterone and estradiol production. 2) In a tracer experiment, Gn-RHa inhibited PMSG-stimulated progesterone production by stimulating 20 alpha-hydroxyprogesterone production. On the other hand, Gn-RHa inhibited estradiol production by inhibiting PMSG-stimulated aromatization. 3) On 20 alpha-hydroxysteroid dehydrogenase activity, it appears that Gn-RHa accelerates the maximum velocity and decreases the affinity of the enzyme to 20 alpha-hydroxyprogesterone as the substrate. (II) In man: 1) In granulosa cells during the ovulatory phase, Gn-RHa inhibited PMSG-stimulated progesterone and estradiol production. 2) In luteal cells, Gn-RHa inhibited hCG-stimulated progesterone production. 3) The affinity of Gn-RH receptor in the corpus luteum was lower than that in rat ovaries. These results suggest that in the human ovary as well as in the rat ovary, Gn-RHa might have a direct effect on the development of the follicle. PMID- 1431440 TI - [Assessment of fetal lung maturity using newly developed immunological measurement of fetal pulmonary surfactant apoprotein-A in amniotic fluid]. AB - The level of immunoreactive lung surfactant apoprotein A (SP-A) was determined with a newly developed one-step ELISA kit (TDR-20) in 217 samples obtained by transabdominal or transvaginal amniocentesis from 217 pregnant women with high risk pregnancy. The lecithin/sphingomyelin ratio (L/S ratio) by two-dimensional thin layer chromatography, disaturated phosphatidylcholine (DSPC) values, shake test and the stable microbubble method were done simultaneously to compare diagnostic reliability in estimating fetal lung maturity. Amniotic fluid SP-A levels increased with advancing gestational age and correlated well with the values obtained by the other methods. When the cut-off SP-A value for the assessment of lung maturity was set at 1,700ng/ml in the amniotic fluid obtained within 24h before delivery, the true-negative rate for RDS was 71% and the true positive rate for non-RDS was 83%. The sensitivity, specificity and accuracy were 100%, 83% and 88%, respectively. These results are comparable with those for the L/S ratio, DSPC determination and the stable microbubble method, and were slightly better than those for the shake test. In conclusion, this newly developed ELISA kit for the measurement of amniotic fluid SP-A is more effective than other methods currently available for the evaluation of fetal lung maturity, when it is considered that it requires only 0.2ml of amniotic fluid and provides results in only 2h without technical difficulties. PMID- 1431441 TI - [Detection of tumor markers in uterine cancer (plasminogen activators, plasminogen activator inhibitors) using fibrin autography]. PMID- 1431443 TI - [Laparoscopy-guided cystectomy of the ovarian cyst]. PMID- 1431442 TI - [The elevated level of brain natriuretic peptide (BNP) in the umbilical cord plasma under with fetal distress]. PMID- 1431444 TI - [Early amniocentesis-risk and laboratory evaluation]. PMID- 1431445 TI - [Clinical and endocrine features of climacteric masked depression]. PMID- 1431446 TI - [The malignant rhabdoid tumor in pregnancy and steroid receptors]. PMID- 1431447 TI - [Serum level of hCG-like substance in the patients of choriocarcinoma can be suppressed by Buserelin-administration]. PMID- 1431448 TI - [The study on the mechanism of sinusoidal fetal heart rate pattern by pulsed Doppler ultrasonographic examination]. PMID- 1431450 TI - [Role of thrombosis and coronary vasospasm in etiology of myocardial infarction]. PMID- 1431449 TI - [Therapy of myocardial infarction in Japan]. PMID- 1431451 TI - [Myocardial reperfusion injuries and stunned myocardium]. PMID- 1431452 TI - [Relationship between unstable angina and acute myocardial infarction]. PMID- 1431453 TI - [Progress on diagnosis of acute myocardial infarction]. PMID- 1431454 TI - [Limitation of ECG for diagnosis of myocardial infarction]. PMID- 1431455 TI - [Progress on biochemical diagnosis of acute myocardial infarction]. PMID- 1431456 TI - [Progress on diagnosis of severity of myocardial infarction]. PMID- 1431457 TI - [Timing of emergency coronary angiography for diagnosis of acute myocardial infarction]. PMID- 1431458 TI - [Diagnosis of myocardial infarction by percutaneous coronary angioscopy]. PMID- 1431459 TI - [Diagnosis of myocardial infarction by PET scan]. PMID- 1431460 TI - [Primary care of patients with myocardial infarction]. PMID- 1431461 TI - [Clinical application of intravenous thrombolytic therapy in acute myocardial infarction]. PMID- 1431462 TI - [PTCR, PTCA for the treatment in patients with acute myocardial infarction]. PMID- 1431463 TI - [Rehabilitation of post-infarction patients]. PMID- 1431464 TI - [Prevention of recurrence of myocardial infarction]. PMID- 1431465 TI - [Thrombolytic therapy of myocardial infarction (discussion)]. PMID- 1431466 TI - [A case of progressive spinal muscular atrophy with disorder of intestinal motility improved by administration of erythromycin]. PMID- 1431467 TI - [A case of pure red cell aplasia with monoclonal gammopathy]. PMID- 1431468 TI - [A case of recurrent syncope due to pulmonary embolism]. PMID- 1431469 TI - [A case of pancreatic ascite with preoperative diagnosis of leaking pancreatic cyst]. PMID- 1431470 TI - [A case of hepatitis due to measles virus]. PMID- 1431471 TI - [Complications of long-term hemodialysis patients and the countermeasures]. PMID- 1431472 TI - A computerised bronchoscopy database providing reporting and auditing facilities. AB - The bronchoscopy reporting and auditing procedure has been computerised using dBASE IV software on a portable microcomputer and printer system. Although entering the data into the computer tends to prolong the reporting procedure slightly, the additional effort is rewarded by a more comprehensive, attractive and accurately documented report; together with rapid access to correct clinical and medical audit statistics. The ease of access to the patient data is proving useful at clinical review meetings and in the production of quality assurance statistics of operator technique. PMID- 1431473 TI - A computerized system for acquisition and evaluation of polysomnographic recordings. AB - A computer system has been designed for acquisition and evaluation of polysomnographic recordings. The aim is to create a system running on a microcomputer emulating all functions of a conventional chart recorder and offering the advantage of making computer assisted evaluations. We have done 87 investigations in the first year of operation and were fully satisfied by the performance of the system. The standard signals we recorded were SaO2, heart rate, respiratory effort, nasal and oral airflow and ECG, as well as EOG, EMG and EEG. Due to this new method, evaluation of the recording can be done in less time than with strip chart recordings and the use of hundreds of pages of paper per night can be avoided. PMID- 1431474 TI - Eight year's experience with automated anesthesia record keeping: lessons learned -new directions taken. AB - For the past eight years, an automated anesthesia record keeping system, COMANDAS (COMputerized ANesthesia Data Acquisition System) has been used in the cardiovascular operating rooms at Mayo Clinic. The automated anesthesia record is designed to match the traditional hand-written record and becomes part of the official medical record. COMANDAS is interfaced with the physiologic monitor and mass spectrometer in each OR, and a number of other computers within the Mayo Medical Center. Since the introduction of COMANDAS over 24,000 surgical procedures have been charted. The anesthesia record is more complete, consistent in organization, and legible when compared to a hand-written record. Recently, it was determined that the computers and peripherals that make up COMANDAS were wearing out and that the vendors would no longer support or replace the equipment. A process to find a replacement for COMANDAS was then begun. Although the cardiovascular anesthesia group was satisfied with the automated anesthesia record, there were a number of areas in which improvement was desired. A systematic evaluation of the system was begun with a survey of the users. The majority of those surveyed felt that COMANDAS was a useful system which made parts of their job easier. The user interface, method of manual data entry, time to produce the record and difficulty learning the system were the source of the greatest dissatisfaction. Artifacts, networking, interfacing with other devices and computers were also issues for the replacement system. Most commercial systems were found wanting in one or more areas of significance. The most practical solution appeared to be the modification of a currently available intensive care unit patient data management system. PMID- 1431475 TI - PADS (Patient Archiving and Documentation System): a computerized patient record with educational aspects. AB - Rapid acquisition and analysis of information in an Intensive Care Unit (ICU) setting is essential, even more so the documentation of the decision making process which has vital consequences for the lives of ICU patients. We describe an Ethernet based local area network (LAN) with clinical workstations (Macintosh fx, ci). Our Patient Archiving and Documentation System (PADS) represents a computerized patient record presently used in a university hospitals' ICU. Taking full advantage of the Macintosh based graphical user interface (GUI) our system enables nurses and doctors to perform the following tasks: admission, medical history taking, physical examination, generation of problem lists and follow up notes, access to laboratory data and reports, semiautomatic generation of a discharge summary including full word processor capabilities. Furthermore, the system offers rapid, consistent and complete automatic encoding of diagnoses following the International Classification of Disease (ICD; WHO, [1]). For educational purposes the user can also view disease entities or complications related to the diagnoses she/he encoded. The system has links to other educational programs such as cardiac auscultation. A MEDLINE literature search through a CD-ROM based system can be performed without exiting the system; also, CD-ROM based medical textbooks can be accessed as well. Commercially available Macintosh programs can be integrated in the system without existing the main program thus enabling users to customize their working environment. Additional options include automatic background monitoring of users learning behavior, analyses and graphical display of numerous epidemiological and health care related problems. Furthermore, we are in the process of integrating sound and digital video in our system. This system represents one in a line of modular departmental models which will eventually be integrated to form a decentralized Hospital Information System (HIS). PMID- 1431476 TI - Inform: conceptual modelling of intensive care information systems. AB - Intensive care of a patient requires heavy monitoring and versatile therapeutic actions. These produce a huge amount of patient information. A problem exists in managing this data and other information from all supporting activities creating a need for an automated information management system. To have a sound basis for future automated information systems in intensive care unit (ICU), a conceptual model is created to cover both the clinical and other activities of the ICU. The conceptual model consists of data flow diagrams and entity-relationship diagrams with underlying common data dictionary. A modern CASE tool is utilized to build the model. The work forms a part of AIM-INFORM project, which has a purpose to develop information management and decision support systems for high dependency environment. PMID- 1431477 TI - Microprocessor-based near real-time bedside blood chemistry monitor. AB - A microprocessor-based instrument which integrates the function of a volumetric infusion pump with a blood chemistry analyzer has been developed. Presently, the instrument is capable of measuring Na+, K+, Ca++ and pH within approximately 40 sec at a frequency of up to every 2 min. The system is set up as an intravenous (IV) infusion pump with the addition of an array of disposable sensors placed at the distal end of the IV set. An isotonic IV solution is used to keep the site patent while also serving as a calibrant for the sensors. The instrument first calibrates the sensors, then withdraws approximately 0.6 ml of blood to come in contact with the sensors. Within approximately 15 sec, it displays the results, flushes the blood back into the patient and resumes normal infusion. There is no blood loss to the patient and no need to handle blood. The system was first validated with known aqueous controls and then used on-line in a variety of animal studies where dynamic fluctuation of electrolytes and pH occurred. Excellent correlation was found with off-line samples tested on conventional STAT analyzers. Some preliminary patient data is also presented. PMID- 1431478 TI - ECG of the month. Triad of doom? Atrioventricular and interventricular block. PMID- 1431479 TI - Primary immunodeficiencies. AB - Primary immunodeficiencies are rare immune system disorders that present with recurrent and chronic infections of the head and neck. Otitis media, sinusitis, and upper respiratory tract infections develop frequently and present in early childhood. The purpose of this report is to classify and define the primary immunodeficiencies as well as to examine the clinical manifestations, evaluation, and treatment of these disorders. PMID- 1431480 TI - Rapidly progressive crescentic glomerulonephritis associated with ANCA (incomplete or variant Wegener's granulomatosis) PMID- 1431481 TI - Measles vaccine for susceptible postpartum women. PMID- 1431482 TI - Assisting in the long term care needs of the person living with HIV. PMID- 1431483 TI - Living wills and orders not to resuscitate: what is the difference? AB - There is confusion about the meaning of living wills and orders not to resuscitate. Both are very important concepts which allow patients to control some of the decisions at the end of life. Living wills are valid until revoked, have the same meaning throughout Louisiana, and are implemented when a patient becomes incompetent and qualified (certified in writing as having a terminal and irreversible condition). Orders not to resuscitate are policy matters in each hospital, thus they vary throughout the state. They are implemented at the time of cardiac arrest. PMID- 1431484 TI - Evaluation of urinary incontinence in the elderly. AB - Urinary incontinence affects millions of elderly American men and women. This paper reviews the causes of urinary incontinence and the evaluation that can be easily accomplished as an outpatient with minimal expense and morbidity. PMID- 1431485 TI - The uses of simulation in anesthesiology training: a review of the current literature. AB - Can anesthesia simulation be used successfully in training to improve the abilities of anesthesiologists and so result in decreased morbidity and mortality due to human error? In this review, computer simulation is examined as a training technique to reduce human error during the administration of anesthesia and as a method for studying how anesthetic accidents occur. Simulation is used successfully in other fields, such as aviation pilot training. A discussion of what defines human error will enable understanding of how computer simulation may be used to reduce it. Simulation of the anesthesia environment has been only recently developed. At this time there are at least two simulators which have been developed for the anesthesia environment. The two simulations are different in that one is strictly computer based. One reproduces the anesthesia monitors using computer graphics. The other, the Comprehensive Anesthesia Simulation Environment (CASE) simulation, attempts to reproduce the entire operating room. These two available simulators are discussed. It is presently unknown whether or not the use of simulation in anesthesia training improves the quality of that training. However, simulators necessary to answer this question are either available now or will be in the near future. PMID- 1431486 TI - The mortality experience of Dow Chemical Louisiana Division employees, 1956-1986. AB - A major objective of the epidemiology department of the Dow Chemical Company is to report at periodic intervals the cause-specific mortality experience of its employees. This study analyzed the cause-specific mortality experience of 4,229 male and female employees of the Louisiana Division who were employed for at least 1 year from 1956 through 1986. Regardless of the comparison population used to calculate expected numbers (United States, Louisiana, or the surrounding five parish area), fewer deaths were observed for all causes combined as well as for all malignant neoplasms, diseases of the circulatory system, and external causes of death. PMID- 1431487 TI - Of physicians and medical decisions concerning the end of life. PMID- 1431488 TI - ECG of the month. A cool-inary problem. Hypothermia. PMID- 1431489 TI - The hard-of-hearing patient in office practice. AB - The hard-of-hearing patient may represent difficult evaluation and management decisions. This article will serve as a review for the primary care physician. Included will be a description of the various types of hearing losses, their causes, evaluation, and treatment. PMID- 1431491 TI - Preoperative management of sickle cell patients. AB - During a 12-year period, 59 patients with sickle cell disease underwent a total of 73 operative procedures. There was a total of 30 non-sickle-cell-related and 7 sickle-cell-related complications for an incidence of 41% and 10% respectively. There were no deaths. When complications were compared between patients that were transfused and those not transfused, there was no difference in the incidence of sickle-cell-related complications with an 8% incidence for the non-transfused group and 10% for the transfused group. A higher incidence of non-sickle-cell related complications (46% versus 32%) was noted in the transfused group, with atelectasis being the most common complication (p = .29). The type of transfusion therapy did not influence morbidity, since the complication rates in the simple and exchange transfusion groups were similar. In conclusion, our data indicate that routine preoperative blood transfusion does not appear to be beneficial in the surgical sickle cell patient, since preoperative blood transfusions did not reduce the incidence of sickle-cell-related complications. PMID- 1431490 TI - Aspiration pneumonia. PMID- 1431492 TI - Putting the 'manage' into managed care. AB - Managed care is part of our modern medical vocabulary just like Medicare and Medicaid were 20 years ago. Other areas of the country are significantly impacted by managed care. Now the concept of businesses and industries representing large numbers of patients and potential patients have become an integral component of nearly every physician in Louisiana. Most physicians are out of their "comfort zone" when contracts with managed care providers are discussed. This article provides guidelines for selecting and solving problems with managed care providers. PMID- 1431493 TI - Common human phobias. AB - The kernel of realistic fear present in the common phobias arises from phylogenetic as well as ontogenetic roots. A phobia's full development depends upon life experience, the role of the symbolization process in expressing personal conflict, and individual temperamental and familial factors. PMID- 1431494 TI - Interleukin-6: on target for disease and approaching the bedside. PMID- 1431496 TI - Dimer formation and desensitization of the epidermal growth factor receptor. PMID- 1431495 TI - Oncogene intervention into hematopoietic signaling. PMID- 1431497 TI - Alcohol consumption in the guinea pig is associated with reduced megakaryocyte deformability and platelet size. AB - Mild thrombocytopenia is common in alcoholic individuals. Ethanol appears to impair platelet production primarily by affecting the maturing megakaryocyte compartment. We recently showed that guinea pigs have an unusually large number of elongated platelet forms even under conditions of steady-state thrombopoiesis, and a portion of their mature (stage IV) megakaryocytes yield extremely long extensions on micropipette aspiration. This study evaluates the effect of a moderately low level of ethanol consumption by guinea pigs on platelet size and form and megakaryocyte deformability. Adult Duncan Hartley guinea pigs took ethanol 2.5% (vol/vol) ad libitum for 4 weeks under environmentally controlled conditions, never reaching detectable blood ethanol levels (< 0.01%); the platelet count fell 16%. Elongated platelet forms constituted 29% of the cardiac puncture platelets of control animals, but only 3% of the cardiac puncture platelets of animals given ethanol; discocytic platelets of ethanol-treated animals were also significantly smaller. Individual stage III and IV megakaryocytes were aspirated into 5 microns diameter micropipettes by stepwise increment in pressure from 10 to 200 cm water. The extensions drawn from megakaryocytes of ethanol-exposed animals were significantly shorter than the extensions from control megakaryocytes. Extremely long extensions over 50 microns in length were drawn from 21% of the control megakaryocytes but less than 1% of ethanol-exposed megakaryocytes. Moderately low level ethanol consumption was associated with reduced platelet count and size, along with rigidity of mature megakaryocytes in guinea pigs. Few ethanol-exposed megakaryocytes yielded extremely long cell extensions, nor were elongated platelet forms prevalent in the circulation of animals given ethanol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431498 TI - Secretion of hyaluronic acid from synovial fibroblasts is enhanced by histamine: a newly observed metabolic effect of histamine. AB - We obtained evidence for the presence of histamine H1 and H2 receptors in normal synovial fibroblasts. Histamine enhanced proliferation of these synovial fibroblasts and stimulated the release of hyaluronic acid from these tissues. The molecular weight of hyaluronic acid decreased with this stimulation. The release of lower molecular weight hyaluronic acid from the synovium by histamine may be an important factor in joint disease. PMID- 1431499 TI - Serum proteins and acid-base equilibria: a follow-up. AB - A mathematic model that described the acid-base behavior of blood plasma has been revised to incorporate pK values of individual histidine residues on human serum albumin determined by nuclear magnetic resonance spectroscopy. With the insights derived from the model a method for evaluation of the strong ion difference has been developed. Thus if pH, PCO2, and the concentrations of serum albumin and phosphate are measured, all independent variables, which physically determine "acid-base balance" in plasma, can be quantified. New ways to evaluate "unidentified anions" in metabolic acidosis can be explored with this approach. PMID- 1431500 TI - Low blood glutathione levels in healthy aging adults. AB - The objective of this investigation was to test the hypothesis that blood glutathione levels are lower in aging human subjects as previously found in blood and tissues of standard rodent models of aging. Thus a study was conducted with 39 men and 130 women, 20 to 94 years old, who were selected by the criteria of being ambulatory, healthy, and free from diabetes mellitus, thyroid disease, anemias, and cancer. The reference group was comprised of the 20- to 39-year-old subjects, whose blood glutathione levels were 547 +/- 53.5 micrograms/10(10) erythrocytes (mean +/- SD) for 40 individuals and defined the reference range (95% confidence limits) of 440 to 654. Based on the 440 micrograms/10(10) erythrocyte cutoff, the incidence of low blood glutathione content in the older subjects increased significantly, particularly in the 60- to 79-year-old group. Their glutathione levels were 452 +/- 86.8 micrograms/10(10) erythrocytes, 17% lower than the reference group (p < 0.001). These findings demonstrate an increased incidence of low glutathione levels in apparently healthy elderly subjects, who thus may be at risk because of a decreased capacity to maintain many metabolic and detoxification reactions mediated by glutathione. PMID- 1431501 TI - The contribution of factor V to the coagulant property of pleural fluid. AB - Intrapleural fibrin deposition commonly accompanies pleural injury and may contribute to the organization of exudative pleural effusions, which leads to lung entrapment. Previous investigators have observed an increase in procoagulant proteins in pleural effusions but very little thrombin formation. FVa is the protein cofactor in the prothrombinase complex that dramatically enhances the generation of thrombin from prothrombin by the serine protease fXa. The presence of fVa within the pleural space could influence fibrin formation and pleural scarification. We examined pleural fluids obtained from patients who had lung cancer, CHF, and empyema for the presence of fV/fVa. The fV antigen was increased in exudative pleural fluids, in comparison with transudates. However, the specific activity of fV antigen present in exudates was significantly less than that observed for the lower concentration of antigen present in transudate and could not be activated to the same degree by thrombin. Immunoblots of fV antigen in exudates indicated that fV was partially cleaved and inactivated by unidentified proteases. We conclude that although fV is present in pleural fluid, it may be present in a degraded form, which may partially account for a lack of thrombin-generating capacity in these pleural fluids. The presence of fV does not necessarily correlate with pleural loculation. PMID- 1431502 TI - Inhibition of the activation of Hageman factor (factor XII) by extracts of Schistosoma mansoni. AB - How intravascular helminth parasites evade host hemostatic defense mechanisms and survive within the circulating blood has not been adequately explained. Previous reports have described an inhibitor of the intrinsic clotting pathway in extracts of adult Schistosoma mansoni. Using a purified preparation of Hageman factor, we examined the ability of schistosome extracts and secretory products to inhibit the activation of human Hageman factor (factor XII) in an amidolytic assay. Both schistosome extracts and secretory products inhibited the activation of purified Hageman factor by more than 95%. Schistosome extracts inhibited activation of Hageman factor both by ellagic acid and by bovine sulfatides. In contrast, activated Hageman factor retained full activity in the presence of schistosome extracts as tested both on an amidolytic synthetic substrate and a natural substrate, plasma thromboplastin antecedent (factor XI). Our findings indicate that extracts and secretory products of adult Schistosoma mansoni contain a potent inhibitor of the activation of Hageman factor. Knowledge of a site at which schistosomes inhibit the intrinsic clotting pathway provides added insight into the mechanisms by which the parasites avoid the host hemostatic defense mechanisms. PMID- 1431503 TI - Respiratory epithelial carbohydrate levels of rats with gram-negative bacillary colonization. AB - One mechanism by which severe illness or stress might facilitate adherence and colonization of GNB to respiratory epithelium is by altering epithelial cell surface carbohydrates. To investigate this possibility we used radiolabeled lectins to quantitate carbohydrate levels on intact buccal and tracheal epithelium. A rat model of GNB colonization, in which renal infarction was performed to produce colonization, was used. Buccal and tracheal epithelial surface carbohydrate levels from normal rats and rats 48 hours after renal infarction were compared. Buccal and tracheal epithelium from the renal infarction animals had decreased amounts of sialic acid and fucose, and decreased levels of these sugars occurred at the same time that heavy oropharyngeal GNB colonization developed. Tracheas obtained from the infarcted animals bound three times more Type 1 piliated GNB than normal tracheas. Sialic acid and fucose levels are decreased early after stress, and we speculate that altered epithelial carbohydrates may predispose to GNB colonization by exposing binding sites for GNB. PMID- 1431504 TI - Effect of enhanced erythropoiesis on iron absorption. AB - To examine the influence of erythropoiesis on iron absorption, radioiron absorption tests were performed in normal subjects before and after a course of recombinant erythropoietin. The absorption of heme and nonheme iron from a standard meal was measured in nine subjects, and the absorption of a therapeutic dose of ferrous sulfate given with or without food was determined in an additional 11 subjects. The subcutaneous administration of 100 U recombinant human erythropoietin/kg body weight given on 10 successive days over a 2-week period induced a brisk increase in erythropoiesis and a sharp decrease in iron stores. With the standard meal, there was a modest increase in heme iron absorption from 47.0% to 58.6% (p < 0.05) and a dramatic five-fold rise in nonheme iron absorption from 5.9% to 31.8% (p < 0.001). The absorption of 50 mg iron as ferrous sulfate increased from 2.0% to 17.9% when given with food (p < 0.001) and from 7.0% to 24.6% when given with water (p < 0.001). To assess the effect of erythropoiesis independently of the induced changes in iron status, the absorption data were adjusted to a common serum ferritin level. The relative increase in iron absorption was still significant for both dietary nonheme iron (ratio 2.51, p < 0.02) and ferrous sulfate given with food (ratio 2.99, p < 0.01). It is concluded that the striking enhancement of iron absorption following regular erythropoietin administration in normal subjects is related to the combined effect of diminished iron stores and augmented erythropoiesis. PMID- 1431505 TI - Detection of properdin mRNA in human peripheral blood monocytes and spleen. AB - Properdin serves a critical role in the alternative pathway of complement by stabilizing the C3bBb complex. Early studies to determine the properdin sequence relied on amino acid sequencing of enzymatically cleaved properdin and only yielded partial sequence data. Recently Nolan et al. reported a properdin mRNA sequence obtained from the U937 myelomonocytic cell line. We sought to detect properdin mRNA in two normal human tissues and to compare those sequences with that obtained from the U937 cell line. Cytoplasmic RNA harvested from human spleen and peripheral blood monocytes served as a template for first strand synthesis. The cDNA was then used as a template for polymerase chain reaction. A properdin message was detected in both spleen and peripheral blood monocytes but not in peripheral blood neutrophils. The sequence was nearly identical to that obtained from the U937 cell line. These experiments demonstrate that peripheral blood may be used as a ready source for properdin mRNA and will faster studies to define the defect in properdin-deficient patients. PMID- 1431506 TI - Histologic studies of splenic megakaryocytes after bone marrow ablation with strontium 90. AB - We previously showed that purified strontium 90 produced sustained bone marrow ablation in mice, lowering platelet levels to less than 10% of normal 11 days after administration. Platelet levels later rose exclusively from splenic production and were maintained at a stable level (58% of normal) from 20 to 115 days after injection. However, there was no change in the total number or ploidy distribution of splenic megakaryocytes, as immunologically detected by flow cytometry. To further study the characteristics of splenic thrombopoiesis after bone marrow ablation by 90Sr, we measured the frequency, cross-sectional area, and endomitotic figures of histologically recognizable megakaryocytes (as well as bare megakaryocyte nuclei) in mouse spleen sections. During the hematopoietic nadir 9 days after injection of yttrium 90-free 90Sr, the size (area) of megakaryocyte cross-sections (mean +/- SD, 1079.3 +/- 661.6 microns 2; normal, 398.7 +/- 192.8 microns 2) was greater than for any other time studied, but megakaryocyte frequency (corrected for size) did not increase until day 16. Overall, splenic megakaryocytes in marrow-ablated mice 16 or more days after 90Sr injection showed substantial increases (p = 0.001 for both comparisons) in mean area (707.5 +/- 386.2 microns 2) and sectional frequency (mean +/- SEM, 4.52 +/- 0.20 per 1.83 mm2; normal, 0.78 +/- 0.06 per 1.83 mm2). Megakaryocyte bare nuclei and endomitotic figures were also more numerous after 90Sr, injection, suggesting acceleration of megakaryocyte maturation and platelet production. The induction of splenic platelet production after bone marrow ablation is associated with increased size of recognizable megakaryocytes, despite lack of change in overall splenic megakaryocyte ploidy. PMID- 1431507 TI - Mitomycin C-induced colitis in rats: a new animal model of acute colonic inflammation implicating reactive oxygen species. AB - The mechanism of the tissue damage induced by colonic inflammation in ulcerative colitis is not established. We therefore developed and characterized a simple new rat model of acute colonic inflammation induced by a single systemic injection of mitomycin C. After an intraperitoneal injection of mitomycin-C, colon histologic examination revealed transient (3 to 14 days) diffuse, colonic inflammation and injury that, like human ulcerative colitis, was limited to the mucosal layer. The rest of the gastrointestinal tract was spared. Gut permeability, as measured by urinary excretion of orally administered lactulose and mannitol, was unchanged 3 days after injection, when inflammation was already present; permeability was increased at 7 days, when inflammation was maximal. Mitomycin C did not produce inflammation in experimentally bypassed segments of small bowel despite the presence of colonic-type bacteria, suggesting that lack of intraluminal bacteria was not responsible for the absence of inflammation in the small intestine. Chemiluminescence, a means of estimating levels of reactive oxygen species, was greater in the intact, inflamed colon of mitomycin C-treated rats than in bypassed segments. Moreover, inflamed mucosal scrapings produced more in vitro luminol-enhanced chemiluminescence. Furthermore, the reactive oxygen species scavengers allopurinol, catalase, and WR-2721 decreased inflammation severity. We therefore conclude: (1) the mitomycin C-treated rat is a novel, easy to prepare animal model of acute inflammation of colonic mucosa, with morphologic similarities to the acute phase of ulcerative colitis in human beings; (2) increased gut permeability in mitomycin C-treated rats is the result, not the cause, of the inflammation; and (3) reactive oxygen species play an important role in colonic inflammation and tissue injury in this model, and possibly in human ulcerative colitis. PMID- 1431508 TI - Inhibition of 11 beta-hydroxysteroid dehydrogenase by gossypol and bioflavonoids. AB - The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) oxidizes hydrocortisone to inactive cortisone in the kidney and is an important regulator of renal K+ clearance. Gossypol, in clinical trials as an antifertility drug for men in China, was associated with episodes of hypokalemia. To learn whether gossypol and other structurally similar compounds in plants can inhibit 11 beta OHSD activity, purified enzyme from rat liver and in human renal cortical microsomes was studied. Rat liver enzyme was inhibited by glycyrrhetinic acid > gossypol >> morin > quercetin >> rutin. Glycyrrhetinic acid, gossypol, and morin inhibited activity of the human kidney enzyme. Enzyme in microsomes from five human kidneys had an IC50 (S.D.) of 1.5 (1.2) mumol/L for glycyrrhetinic acid; enzyme in microsomes from six human kidneys had a 50% inhibitory doses of 147 (25) mumol/L for gossypol. Our observations indicate that gossypol and other compounds in plants can inhibit 11 beta-OHSD activity and may thereby increase K+ excretion. PMID- 1431509 TI - Does lead play a role in Paget's disease of bone? A hypothesis. PMID- 1431510 TI - Assessing response to thrombolytic therapy. PMID- 1431511 TI - Conservative or reconstructive microsurgery of the middle ear. PMID- 1431512 TI - Ear, nose and throat in Ancient Egypt. PMID- 1431513 TI - Vestibular neurectomy by the infralabyrinthine approach. AB - There are a variety of approaches for treating vertigo with selective vestibular neurectomy but each has definite limitations proving that no ideal technique is yet available. An original posterior-inferior approach to the internal auditory canal (infralabyrinthine approach) has been recently proposed. It attempts to overcome the limitations and to combine the advantages of the previous procedures. This report presents our preliminary results using this particular technique in the management of vestibular symptoms of Meniere's disease. PMID- 1431514 TI - The effect of epidural anaesthesia and size of spinal needle on post-operative hearing loss. AB - Forty-five patients who were to undergo elective urological operations were evaluated. In the pre-operative period and on the third or fourth post-operative day audiometry was performed. Epidural anaesthesia was performed in 15 cases, spinal anaesthesia was performed in 15 cases with 25 G needles, and in 15 cases with 22 G needles. No statistically significant hearing loss was observed in the post-operative period compared to preoperative period in the epidural anaesthesia group. In the post-operative period, the hearing loss observed in the 25 G-spinal anaesthesia group was significantly (P < 0.01) less than that seen in the 22 G group. None of the patients had headache after spinal anaesthesia. It was concluded that pure tone audiometry is a more sensitive indicator of cerebrospinal fluid leakage than post-operative headache. PMID- 1431515 TI - A conservative approach to the management of otitis media with effusion in cleft palate children. AB - Otitis media with effusion (OME) is almost universal in children born with a cleft palate. Early placement of a ventilation tube to alleviate hearing problems is common. A retrospective study has been carried out to assess whether the practice of tube placement only for definite clinical indications is successful in terms of subsequent hearing levels and speech and language development. This was assessed by a case note review, analysis of speech therapy data and by means of a special follow-up clinic. There was no difference in speech development between those treated with tube insertion for OME and those untreated. Audiological thresholds were worse in the treated group. A similar number in each group required regular speech therapy. More abnormal otological findings were present at follow up in those who had tubes inserted, some of these were directly attributable to the presence of tubes. A conservative management of OME in cleft palate children, with tube insertion for only definite clinical indications, is an appropriate management, and will lead to fewer otological complications of tube insertion. PMID- 1431516 TI - Surgery of the 'only hearing ear' with chronic ear disease. AB - The management of chronic ear disease affecting the only hearing ear is a controversial subject. The relative scarcity of literature on the subject prompted us to prepare a questionnaire which was sent to European and American otologists and to review 19 cases operated at the ENT Clinic of the University of Parma, Italy, and 16 cases operated at The Baptist Memorial Hospital, Memphis, U.S.A. Surgery of cholesteatoma involving the only hearing ear is advised by all the interviewed otologists without exception, even in the presence of a labyrinthine fistula. The cases from the University of Parma were managed as follows: a classic modified radical mastoidectomy was performed in 10 cases, a staged intact canal wall tympanoplasty was done in four cases, an open tympanoplasty in three and a radical mastoidectomy in the remaining two cases. The cases from The Baptist Memorial Hospital were managed with an intact canal wall tympanoplasty (ICWT) in nine and with an open procedure in seven cases. All the otologists interviewed agreed that surgery of the only hearing ear requires particular attention and experience, and should be performed with extreme care by a very experienced surgeon. PMID- 1431517 TI - Allergic aspergillus sinusitis with proptosis. AB - Allergic aspergillus sinusitis has recently been increasingly recognized. Five cases are discussed. All presented with proptosis, signs and symptoms of allergic rhinitis and radiological evidence of expansile masses with calcification and bony erosions involving multiple sinuses. Greenish cheesy material was seen at surgery. Histologically the lesions contained eosinophils, Charcot-Lyden crystals and fungal septate hyphae. Aspergillus fumigatus was grown from all cases. Surgical removal with drainage and aeration were performed. The follow-up period ranged between three to 18 months. Recurrence occurred in one patient. Allergic aspergillus sinusitis can mimic malignant disease and should be considered in the differential diagnosis of lesions involving multiple sinuses. It should also be considered in all cases of proptosis. PMID- 1431518 TI - Spontaneous pain in patients with maxillary sinus carcinoma in relation to T classification and direction of tumour spread. AB - Spontaneous pain was one of many complaints on initial examination of 845 patients with maxillary sinus carcinoma. The pain was analysed; cheek, teeth, head and eye pain were compared with the T-classification and the anterior posterior direction of invasion. The incidence of the cheek, teeth, head and eye pain was 48, 39, 29 and 23 per cent respectively. The incidence of both the cheek and teeth pain was increased according to the advancement of T-classification and invasion towards the posterior. Head and eye pain was often referred. In the localized posterior group which tend to be diagnosed late, spontaneous pain occurred in 15 to 48 per cent of the patients. Maxillary sinus carcinoma should always be a differential diagnosis in patients with unclear cheek, teeth, head and eye pain. A careful investigation should be performed in order to diagnose malignant diseases as early as possible. PMID- 1431519 TI - Ethmoidal scleroma: endoscopic diagnosis and treatment. AB - Twenty patients with medically treated rhinoscleroma and residual ethmoidal manifestations were examined using CT scanning. Cases with positive radiological data of the ethmoids underwent diagnostic and therapeutic nasal endoscopy. It has been found that ethmoidal scleroma is not as rare a condition as was previously thought. The diagnostic and therapeutic value of nasal endoscopy in ethmoidal scleroma is discussed. PMID- 1431520 TI - Long-term effects of topical corticosteroids in the nose. AB - In a prospective study, biopsies were taken from the septal mucosa in 21 patients of whom 11 had been using topical nasal corticosteroids. In contrast to the effect of long-term treatment with corticosteroids in the skin, but in accordance with previous investigations of the nasal mucosa, no histopathological changes of significance were found, although the biopsies were taken from different sites. These findings do not suggest that topically corticosteroids are harmful to the nasal mucosa. PMID- 1431521 TI - Penetrating injuries to the oropharynx. AB - A review was made of 12 cases of penetrating injuries to the oropharynx seen at Musashino Red Cross Hospital during the period from 1984 to 1988, and their records were compared with those of past cases with similar injuries reported in a survey for the period between 1949 and 1959. Most of the patients were children under the age of four and were injured when they fell with a sharp-edged object in the mouth. Penetrating injuries to the oropharynx occasionally cause severe complications, including retropharyngeal abscess and mediastinitis. This type of injury should be called a 'pencil injury'. PMID- 1431522 TI - Guillotine and dissection tonsillectomy in children. AB - Tonsillectomy as an outpatient or same day-stay procedure is becoming increasingly popular. A retrospective study was performed on 1,049 children who underwent tonsillectomy and adenotonsillectomy either with guillotine or dissection with snare method. The dissection method was performed both under general anaesthesia and with local anaesthesia, but the guillotine method was performed only with local anaesthesia. Generally, bleeding control required no special intervention in the guillotine method but haemostasis was achieved by ligation and electrocauterization in one-third of the patients in the dissection group operated under general anaesthesia. The greatest percentage of haemorrhage in both methods occurred within the first four post-operative hours. There was a 1.8 per cent incidence of severe reactive haemorrhage required surgical intervention in the dissection group operated under general anaesthesia, but there was no such case in the guillotine group. The results of this study show that in carefully selected children guillotine tonsillectomy with local anaesthesia is a safe, time saving and cost-effective procedure. PMID- 1431523 TI - Fibromatosis on the dorsum of the nose. AB - An extremely rare case of fibromatosis in a 25-year-old Indian male is reported. The clinical examination and pre-operative findings were suggestive of a benign neoplasm, probably of neurogenic origin. The mass was well circumscribed and could be shelled out en masse. Histopathological examination showed it to be fibromatosis. An external rhinoplasty approach enabled a complete wide excision to be performed without any resulting cosmetic defect. PMID- 1431525 TI - Adrenal suppression with intranasal betamethasone drops. AB - Intranasal betamethasone sodium phosphate drops (Betnesol) are frequently used to relieve nasal congestion due to polyposis. We report a case of significant hypothalamic-pituitary-adrenal suppression secondary to the long-term use of intranasal betamethasone drops. This case emphasizes that the topical application of potent corticosteroids may produce systemic effects. PMID- 1431524 TI - Nasopharyngeal Corynebacterium ulcerans: a different diphtheria. AB - A case of toxigenic Corynebacterium ulcerans infection is presented. The diagnosis was delayed and no anti-toxin administered. A nasopharyngeal biopsy was complicated by severe haemorrhage necessitating a post nasal pack. A brief review of the pathology and treatment of Corynebacterium ulcerans is given. PMID- 1431526 TI - Use of the carbon dioxide laser with the Montgomery T-tube in the management of extensive subglottic stenosis. AB - Subglottic and tracheal stenosis frequently present difficulties in management. Two cases of subglottic stenosis occurring after prolonged endotracheal intubation are presented where the vertical length of complete obstruction by scar tissue was greater than 2.5 cm. One case was successfully managed by the use of the laser and immediate insertion of a stent. The other case still requires subglottic stenting, although an excellent lumen was established by laser vaporization of the stenosed segment. PMID- 1431527 TI - Cisplatin-albumin complex for treatment of cancer of the head and neck. AB - Many patients with cancer of the head and neck are unable to receive or continue treatment with cisplatin, which is nephrotoxic, because of poor renal function. We present here, however, the case of a patient who underwent conventional cisplatin therapy but who then had to be withdrawn from treatment because of renal toxicity despite having undergone partial remission. Treatment was then changed to cisplatin in the form of a cisplatin-albumin complex which is not nephrotoxic. The patient went on to a histologically confirmed complete response and we suggest that although the cisplatin-albumin complex may not be as effective as the conventional form of the drug it offers a possible form of treatment of patients with compromised renal function who could not otherwise be treated. PMID- 1431528 TI - An amalgam tattoo of the soft palate: a case report with energy dispersive X-ray analysis. AB - A pigmented lesion of the soft palate was excised to exclude melanoma. The histology suggested an amalgam tattoo which was confirmed on energy dispersive X ray analysis by the detection of silver and copper. This represents a very rare mimic of melanoma of the soft palate. PMID- 1431529 TI - Teratoma of the head and neck. PMID- 1431530 TI - Isolated bilateral paralysis of the soft palate in an adult. AB - A case of bilateral paralysis of the soft palate occurring in a 42-year-old patient is presented. Idiopathic paralysis of the soft palate as an isolated clinical entity was first described by Edin et al. 1976. Since then 22 similar cases have been reported, all in children and all unilateral. A search of the English language literature has not revealed a case of bilateral palatal palsy in an adult. PMID- 1431531 TI - Relapsing polychondritis--two cases with tracheal stenosis and inner ear involvement. AB - Relapsing polychondritis is a rare disease which often presents firstly to ear, nose and throat (ENT) departments. Its complications, respiratory, cardiovascular, renal and neurological are life-threatening; thus it is important to recognize the disease and its complications early. Treatment for relapsing polychondritis may have serious side-effects which should be taken into account when managing these patients. We report two young patients with relapsing polychondritis and their treatments; both had severe tracheal stenosis responding in one case to pharmacological and in the other to surgical intervention. PMID- 1431532 TI - Laryngo-tracheo-bronchopathia chondro-osteoplastica. AB - Two cases of laryngo-tracheo-bronchopathia chondro-osteoplastica (LTBCOP) are discussed regarding the pathogenesis of the disease. Our observations support the belief that chronic irritation of the perichondrium in the region of subglottis, trachea and bronchi plays an important role in the aetiology of this disease. PMID- 1431533 TI - Alternative methods of application of topical preparations in otitis externa. PMID- 1431534 TI - Alternative methods of application of topical preparations in otitis externa. PMID- 1431536 TI - Alternative methods of application of topical preparations in otitis externa. PMID- 1431535 TI - Alternative methods of application of topical preparations in otitis externa. PMID- 1431537 TI - The validity of distinguishing children with language and learning disabilities according to discrepancies with IQ: introduction to the special series. PMID- 1431538 TI - The validity of discrepancy criteria for identifying children with developmental language disorders. AB - Empirical data from two studies address the clinical validity of discrepancy criteria for identification of children with developmental language disorders (DLD). Study 1 involved 256 preschoolers clinically defined as DLD and meeting inclusionary criteria for normal hearing, intellectual, neurological, and psychiatric status. Application of alternative psychometrically derived discrepancy criteria identified only 40% to 60% of the clinically defined group as language disordered. Study 2 applied nonverbal IQ-language performance discrepancy criteria to 368 eight-year-old, randomly selected control subjects, resulting in over 45% of the controls being identified as DLD. Factors contributing to underidentification in Study 1 and over-identification in Study 2 are discussed, raising questions regarding the validity of discrepancy criteria for identification of DLD children. PMID- 1431539 TI - The validity of discrepancy-based definitions of reading disabilities. AB - This study addressed the validity of distinguishing children with reading disabilities according to the presence or absence of discrepancies between intelligence test scores and academic achievement. Three definitions of reading disability were used to provide criteria for five groups of children who (a) met a discrepancy-based definition uncorrected for the correlation of IQ and achievement; (b) met a discrepancy-based definition correcting for the correlation of IQ and achievement; (c) met a low achievement definition with no IQ discrepancy; (d) met criteria a and b; and (e) met none of the criteria and had no reading disability. Comparison of these five groups on a set of 10 neuropsychological tests corrected for correlations with IQ showed that group differences were small and accounted for little of the variability among groups. These results question the validity of segregating children with reading deficiencies according to discrepancies with IQ scores. PMID- 1431540 TI - The external validity of age- versus IQ-discrepancy definitions of reading disability: lessons from a twin study. AB - Recent research has raised the question of whether age- and IQ-discrepancy forms of reading disability (RD) are distinguishable in terms of either their underlying linguistic deficit or their response to treatment, thus threatening the external validity of the traditional distinction between specific reading retardation and reading backwardness. The present study pursued the external validity of this distinction in three domains: (a) genetic etiology, (b) sex ratio and clinical correlates, and (c) neuropsychological profiles. Each of these domains was explored in the RD (n = 640) and control (n = 436) twins participating in the Colorado Reading Project (514 males, 562 females, with an overall mean age of 12.42 years). Little evidence for external validity was found in terms of the clinical correlates of attention deficit-hyperactivity disorder (ADHD), immune disorders, or handedness. Most importantly, there was no evidence of differential genetic etiology of the two phenotypes in this sample, in that deficits in both phenotypes were similarly heritable (h2g = .40 and .46 for age and IQ phenotypes, respectively) and the genetic correlation between them was high (rG = .88 to .96). However, the genetic and neuropsychological profile analyses did suggest that age- and IQ-discrepancy definitions of RD may relate differentially to component reading processes, such as phonological awareness and orthographic coding. PMID- 1431541 TI - Diagnosing dyslexia: IQ regression plus cut-points. PMID- 1431542 TI - Language abilities, reading acquisition, and developmental dyslexia: limitations and alternative views. PMID- 1431543 TI - Students' expectations about peer pressure to engage in misconduct. AB - Previous research suggests that students with learning disabilities may differ from other students in their expectations of how peers are likely to propose engaging in misconduct. This study followed up on these findings using a methodology that did not require the participants to produce their responses verbally. Participants were 74 students with learning disabilities (53 male, 21 female) and 85 students without disabilities (40 male, 45 female) from high schools in three types of communities (urban, primarily black; urban, primarily Hispanic; suburban, primarily white). The students were presented with a series of pairs of statements that might be made by a teenager trying to entice a peer into misconduct and were asked to indicate which statement in each pair was the more persuasive. The results partially replicated the earlier research. The methodological and social implications of these results are discussed. PMID- 1431544 TI - Pedigree analysis of children with phonology disorders. AB - This study examined 87 pedigrees of individuals with histories of preschool phonology disorders. Results confirmed previous reports that speech and language disorders aggregate in families, with a higher incidence of males affected than females. Significantly more family members with dyslexia and learning disabilities, but not stuttering or hearing impairment, were found in pedigrees of individuals with phonology disorders than in pedigrees of nondisabled individuals. Probands with and without additional language problems did not differ in the incidence of affected family members. Nuclear family members demonstrated a higher incidence of disorders than when all family members were considered, with brothers of probands most often affected. Pedigrees of female probands had more affected members in their nuclear families than pedigrees of male probands. PMID- 1431545 TI - Tourette syndrome and learning disabilities. AB - We reviewed the records of 42 consecutive cases of children with Tourette Syndrome (TS) who had IQs above 70, and contrasted the reading, reading comprehension, math, and spelling quotients with IQ scores to determine how many would meet criteria for a learning disability. The mean IQ of the 35 males and 7 females was 94.4 and was higher than the mean math score (82.8), spelling score (90.4), reading score (87.4), and reading comprehension score (85.3). Using a 1.5 standard deviation discrepancy, 51% met criteria for learning disability in at least one academic area; 21% had a 2-standard-deviation discrepancy. Children with TS frequently have learning disabilities, and assessment of academic achievement should be a routine aspect in the evaluation of such children. PMID- 1431546 TI - Specific reading impairments--are they to be associated with emotional difficulties? AB - The assumption that specific learning disabilities are not causally related to emotional disturbances is crucial for the cognitive research approaches that endeavor to isolate specific malfunctioning cognitive-computational processes. Because there are conflicting data regarding the emotional status of subjects with learning difficulties, the purpose of this study was the evaluation of the emotional status of subjects with specific learning difficulties in comparison with that of subjects from several relevant control groups. The HSCL-90 profiles of 38 subjects suffering developmental dyslexia, 28 subjects with subjective complaints regarding general concentration and reading comprehension difficulties, and 23 psychiatric patients were compared with those of 44 skilled readers without any known emotional difficulties. All subjects were adolescents and young adults (age range = 15 to 23). A cluster analysis of subjects' HSCL-90 profiles did not reveal any significant differences between subjects with dyslexia and control subjects. Both groups, on the other hand, were easily differentiated from psychiatric patients. Subjects with severe deficits in their ability to remember details of a text, and with subjective complaints regarding concentration difficulties, tended to generate emotional profiles that testify to a high level of anxiety. Although these subjects, as well as individuals with dyslexia, may be regarded at the functional level as inefficient readers, the two groups seem to clearly differ regarding the failure factors that underlie their phenotypic difficulties. PMID- 1431547 TI - Differences in arachidonic acid metabolism by human myelomonocytic cell lines. AB - The production of arachidonic acid metabolites by the HL60, ML3, and U937 human phagocyte cell lines was determined after incubation with interferon-gamma (IFN gamma, 500 U/ml) or vehicle for 4 days. Cells were prelabeled with tritiated arachidonic acid, [3H]AA, for 4 h, and media supernatants were analyzed by high performance liquid chromatography. None of the cell lines produced [3H]AA metabolites in large amounts during an unstimulated, basal release period (30 or 60 min). In response to 10 microM calcium ionophore A23187 incubation (30 min), undifferentiated and IFN-gamma-differentiated HL60 cells formed both cyclooxygenase products (thromboxane and prostaglandins) and lipoxygenase products (leukotrienes and hydroxyeicosatetraenoic acids). In contrast to the HL60 cells, IFN-gamma-differentiated U937 cells formed primarily cyclooxygenase products and undifferentiated and IFN-gamma-differentiated ML3 cells did not form any [3H]AA metabolites in response to A23187. These results indicate the need to be careful in selecting a cell line for use in a phagocyte assay system when cyclooxygenase and/or lipoxygenase products could influence the assay results. PMID- 1431548 TI - In vivo testing confirms a blunting of the human cell-mediated immune mechanism during space flight. AB - The cell-mediated immune (CMI) mechanism was evaluated in 10 space shuttle astronauts by measuring their delayed-type hypersensitivity response to seven common recall antigens. The Multitest CMI test system was used to administer antigens of tetanus, diphtheria, Streptococcus, Proteus, old tuberculin, Candida, and Trichophyton to the forearm 46 h before nominal mission termination; readings were conducted 2 h after landing. The mean number of reactions was reduced from 4.5 preflight to 3.0 inflight, and the mean reaction score was reduced from 21.4 to 13.7 mm inflight. The data presented suggest that the CMI system is still being degraded by space flight conditions on day 4 and that between day 5 and day 10, the depression maximizes and the system begins to adjust to the new conditions. The relation of these in vivo findings to previously reported in vitro results is discussed. PMID- 1431549 TI - Steroidal nonspecific esterase metabolism of N-hydroxy-2-acetylaminofluorene: evidence for selective activation by the cellular reductant NADPH. AB - The significance of the nonspecific esterases of human mononuclear leukocytes (HMLs) in arylamine carcinogenesis is suggested by data showing that the metabolically formed hydroxamic acid derivative of 2-acetylaminofluorene, N hydroxy-2-acetylaminofluorene, is a substrate for this class of enzymes. A viable cell assay for the nonspecific esterases using alpha-naphthyl acetate as substrate is described, and data showing this activity to be sensitive to already known substrates for HML esterases as measured by three previously described assays are presented. All four assays of the same esterase activity are shown to be highly sensitive to up- and down-regulation by addition of NADPH or NADP to viable HML cultures. Selective activation of a purified rabbit nonspecific esterase by NADPH, but not by the other cellular reductants, NADH and glutathione, was demonstrated. Cytosols prepared from normal human tissue samples of liver, breast, colon, and brain were also activated by the presence of NADPH. These data do not indicate that steroidal nonspecific esterases are redox modulated by the presence of mixed disulfides in their structure. Instead, they support the direct and specific influence of NADPH as a widespread activator of esterase activity by a mechanism not yet understood. PMID- 1431550 TI - Increase in the rat blood leukocyte counts induced by PAF-acether is suppressed by general anesthesia. AB - Blood leukocyte count alterations induced by PAF-acether in anesthetized and nonanesthetized rats were investigated. Intravenous injection of increasing amounts of PAF-acether (1.5-8 micrograms/kg) in nonanesthetized animals induced dose-dependent hemoconcentration and leukocytosis. The former was apparent within 10 min, peaked from 30 min to 1 h, and diminished thereafter. The leukocytosis was noted within 30 min, was maximal at 1 h, and was over 4 h after injection of PAF-acether (4 micrograms/kg). It was characterized by a marked increase in the blood neutrophil counts under conditions in which the number of lymphocytes, monocytes, and eosinophils remained unchanged. PAF-acether-induced leukocytosis occurred in parallel with a marked decrease in the number of bone marrow nucleated cells, suggesting that the latter phenomenon may determine the former one. Leukocytosis by PAF-acether was inhibited dose-dependently by specific PAF acether antagonists including BN 52021 (median effective dose ED50 = 4.99 mg/kg), WEB 2086 (ED50 = 4.59 mg/kg), and 48740 RP (ED50 = 9.02 mg/kg). General anesthesia by either pentobarbital, urethane, or ether inhalation, but not by ketamine, also impaired the PAF-acether-induced blood leukocytosis under conditions in which the hemoconcentration was not modified. In addition, pentobarbital-anesthetized rats did not have reduced bone marrow nucleated cell counts after PAF-acether stimulation. These findings are consistent with the assessment that PAF-acether-induced rat leukocytosis is accounted for by a bone marrow neutrophil mobilization process that is clearly suppressed in animals anesthetized by pentobarbital. PMID- 1431551 TI - Macrophage and lymphocyte functions are down-regulated in newborn rabbits. AB - We have developed an animal model for congenital syphilis. Treponema pallidum is injected intravenously into pregnant rabbits and fetuses are infected in utero. As a prelude to characterizing the immunologic consequences of fetal infection, it was necessary to expand on the baseline information about newborn rabbit immune capabilities. Studies were undertaken to determine splenic macrophage and T lymphocyte functions with emphasis on newer immunologic parameters. Newborns aged 2 weeks were compared to adults. Macrophage capabilities in newborn rabbits differed from those of their adult counterparts. These cells produced similar basal levels of interleukin 1 (IL-1) but failed to respond to the IL-1 stimulants of lipopolysaccharide (LPS) or T. pallidum. Macrophages also exhibited diminished levels of la expression and increased levels of prostaglandin E2 (PGE2) secretion. T lymphocyte functions were altered in newborn spleen preparations. Following concanavalin A (Con A) stimulation, interferon gamma production was half that of adults; in direct contrast, IL-2 production was twice that of adults. Con A-induced lymphocyte proliferation was markedly decreased in newborn preparations. This diminished response resulted from down-regulation rather than immaturity. When newborn splenic cells were stimulated with Con A in the presence of indomethacin, anti-transforming growth factor (anti-TGF), or exogenous IL-1/IL 2, better proliferation resulted. PGE2, which is well established as a down regulator of newborn immune functions in human and mouse systems, also appears to play a role in suppressing newborn rabbit functions. TGF is a potent suppressor of a number of adult immunologic reactions. This is the first documentation of the potential role of this factor in down-regulating newborn immune capabilities. These findings provide a framework for future investigations of our congenital syphilis model. PMID- 1431552 TI - The up- and down-modulation of immunoglobulin G Fc receptors and complement receptors on activated human neutrophils depends on the nature of activator. AB - Human neutrophils were activated with soluble stimuli, formyl-methionyl-leucyl phenylalanine (fMLP) or ionophore A23187, and with opsonized particles, zymosan or Streptococcus pneumoniae bacteria. Monoclonal antibodies and flow cytometry were used to assess the expression of Fc-gamma receptors (FcRI, FcRII, FcRIII) and complement receptors (CR1, CR3). The role of extracellular calcium and magnesium in the modulation of receptor expression was also examined. The low level expression of FcRI was not affected by any activator tested. fMLP and A23187 did not alter the expression of FcRII, whereas a significant, Ca(2+)- and Mg(2+)-independent down-modulation was observed upon activation with opsonized particles. All activators clearly decreased the surface expression of FcRIII in the presence of Ca2+ and Mg2+, probably as a consequence of shedding of the phosphatidylinositol-glycan-anchored receptor protein. The removal of calcium and magnesium blocked the shedding of FcRIII caused by soluble stimuli, whereas it retarded but did not abolish the fall in FcRIII expression when cells were incubated with opsonized particles. This fall was likely due to internalization of the receptor molecules while the shedding was blocked. A rapid increase in CR1 and CR3 expression was seen upon activation with soluble stimuli. The change in CR1 expression was independent of extracellular Ca2+ and Mg2+. The increase in CR3 number required an influx of divalent cations. No total up-modulation of complement receptors occurred when neutrophils were activated with opsonized particles. However, the kinetic analysis revealed a temporary up-modulation that was followed by a down-modulation. The results indicate that the expression of both Fc-gamma and complement receptors on human neutrophils is changed upon activation and that the up- and down-modulation of these receptors depends on the nature of activator. We also suggest that in neutrophils the FcRIII down modulation is the result of both receptor shedding and internalization, while FcRII is down-modulated by receptor internalization. PMID- 1431553 TI - Chronic granulomatous disease with partial deficiency of cytochrome b558 and incomplete respiratory burst: variants of the X-linked, cytochrome b558-negative form of the disease. AB - Five male patients from four different families presented with a clinical record of chronic granulomatous disease (CGD): recurrent infections of the skin and/or respiratory tract with catalase-positive microorganisms, sometimes in combination with granulomata and/or abscesses in various organs. These patients differed from "classical" forms of the disease in that their neutrophils, although deficient in killing in vitro of Staphylococcus aureus, contained a decreased but measurable amount of cytochrome b558 (10-60% of normal on a heme basis), causing weak staining in the nitroblue tetrazolium dye test and a depressed respiratory burst after contact of the cells with fluid or particulate activators of the NADPH:O2 oxidoreductase. In the cell-free activation system, the defect in the patients' cells was localized in the membrane fraction. In each of the four families, the cellular abnormalities showed an X-linked inheritance. Fusion experiments performed with the monocytes from these patients and those from patients with classical X-linked, cytochrome b558-negative (Xb(0)) or autosomal, cytochrome b558-positive (Ab+) CGD showed complementation of NADPH:O2 oxidoreductase activity in the latter but not in the former combination. Thus, the unusual CGD patients represent variant forms of Xb(0) CGD, with mutations in the gene coding for the beta subunit of cytochrome b558 that do not cause complete loss of this protein. PMID- 1431554 TI - Granule-associated flavin adenine dinucleotide (FAD) is responsible for eosinophil autofluorescence. AB - Unstained human eosinophils exhibit marked autofluorescence in comparison to other leukocytes due to a granule-associated fluorescent substance. Fluorescence spectroscopy of granule extracts reveals excitation maxima at approximately 380 and approximately 450 nm with a single emission at approximately 520, characteristic of flavins. The fluorescent material from eosinophil granule extracts was characterized by fluorescence, high-performance liquid chromatographic, and enzymatic analyses. First, acidification to pH 2.6 resulted in increased fluorescence, indicative of flavin adenine dinucleotide (FAD). Second, because flavin mononucleotide (FMN) and riboflavin cannot be distinguished by acidification, high-performance liquid chromatography was performed and revealed a predominance of FAD and smaller amounts (< 15%) of both FMN and riboflavin. Third, the presence of FAD was clearly demonstrated by reconstitution of the activity of D-amino acid oxidase, a FAD-dependent enzyme, when granule extracts were added to the apoenzyme. Thus, we have identified FAD as the predominant fluorophore in eosinophil granules. The small amounts of FMN and riboflavin detected may result from the hydrolysis of FAD under the acidic conditions of granule extraction. Because fluorescent material is deposited onto target cells by eosinophils, it is possible that granule-associated flavoproteins may act as a source of hydrogen peroxide and/or superoxide, which, in conjunction with eosinophil peroxidase, could yield potent cytotoxic agents. PMID- 1431555 TI - Transcriptional inhibition of endotoxin-induced monokine synthesis following heat shock in murine peritoneal macrophages. AB - The role of heat shock proteins (HSP) during the inflammatory response has been controversial. The effect of heat shock (HS) on the synthesis of the monokines tumor necrosis factor (TNF) and interleukin 1 (IL-1) by endotoxin-stimulated thioglycollate-elicited peritoneal macrophages was investigated. HS was deemed to have affected macrophages if a 70 kD HSP appeared on SDS gels; identity of this protein as the highly conserved HSP70 was then confirmed by immunoprecipitation. Maximal increases in HSP70 were apparent 2-5 h after HS at 45 degrees C for 12 min. Synthesis of HSP70 was no longer detected 24 h post HS. A reciprocal relationship between HSP70 and TNF was apparent in kinetic studies. TNF was not detected in culture supernatants if macrophages were endotoxin-stimulated 2 to 6 h after HS; however, the same stimulation 24 h later induced significant TNF secretion. RNA analysis of HS and non-HS macrophage cultures demonstrated a 60 fold reduction in TNF message in the HS macrophages 1 h after endotoxin stimulation. TNF mRNA levels remained depressed at 6 h while the HSP70 message had increased 30-fold. The ability of HS macrophages to ingest antibody-coated erythrocytes was not significantly affected following heat treatment. Macrophage response to HS can be said to inhibit transcription of inducible monokines while retaining other macrophage functions. PMID- 1431556 TI - Ovine mononuclear phagocytes in situ: identification by monoclonal antibodies and involvement in experimental pyogranulomas. AB - In order to characterize in situ the macrophages present in experimental pyogranulomas induced in lambs with Corynebacterium pseudotuberculosis, a set of monoclonal antibodies (MAbs) was produced following immunization of BALB/c mice with alveolar macrophages from healthy sheep. Three MAbs were retained after two steps of screening using alveolar macrophages, peripheral blood lymphocytes, and polymorphonuclear leukocytes as target cells. Their reactivity was tested not only on macrophages in pyogranulomas but also on sections of various organs in steady-state conditions. One MAb, termed OM1, recognized the monocytes and the majority of cells of the mononuclear phagocyte system in lymphoid and nonlymphoid organs. The two other MAbs, OM2 and OM3, reacted with a subpopulation of alveolar macrophages and with other cell types in tissues, in particular with endothelial cells for the MAb OM2. On sections of experimental pyogranulomas that developed in lymph nodes draining the C. pseudotuberculosis-injected sites, MAb OM1 reacted with all the macrophages distributed in a palisade surrounding the necrotic center of the lesion from day 6 to day 28 postinoculation. The two other MAbs, OM2 and OM3, enabled two types of granulomas to be distinguished: one type was characterized by a large number of epithelioid cells stained by OM2; and the other was characterized by a few OM2-positive macrophages, whereas the OM3 positive cells were more numerous. These results show that macrophages are predominant cells in pyogranulomas and suggest two different histological patterns in the evolution of pyogranulomas induced by C. pseudotuberculosis, according to the immunological status of the host. PMID- 1431557 TI - Effects of Pseudomonas aeruginosa rhamnolipids on human monocyte-derived macrophages. AB - Pseudomonas aeruginosa, a major opportunistic gram-negative pathogen, produces and secretes two heat-stable hemolytic glycolipids, a monorhamnolipid and a dirhamnolipid. In this paper a simplified method for the isolation of these rhamnolipids is described. The effect of these two rhamnolipids, both together and individually, on the viability and structural morphology of human monocyte derived macrophages (MDMs) was examined. These cells were found to be very susceptible to the cytolytic activity of the rhamnolipids, particularly the dirhamnolipid. The monorhamnolipid, although not as cytolytic as the dirhamnolipid, caused extensive blebbing of the MDM plasma membrane. Comparison studies with several detergents confirmed the different yet distinct detergent like activity of each rhamnolipid form. At sublethal doses, the rhamnolipids produced marked cellular distortions of the MDMs and inhibited the ability of these cells to bind and/or ingest preopsonized bacteria. The potential mechanism of action of these rhamnolipids on the MDM membranes is discussed, as well as the possible significance of these extracellular bacterial glycolipids as a virulence factor in the pathogenesis of P. aeruginosa. PMID- 1431558 TI - Direct evidence for release of pore-forming protein during NK cellular lysis. AB - In the present study, we have examined the exocytosis model for cellular lysis. Using monoclonal antibodies reactive with human pore-forming protein (PFP), we examined the localization of PFP at the interaction site of natural killer (NK) cells and the NK tumor targets K562 and Molt-4 as well as during antibody dependent cellular cytotoxicity. Following the interaction of effector-target cell contact, an increased frequency of PFP was detected on the effector surface, in the micro-environment, and on the target surface of the interaction site. This temporal deposition of PFP was paralleled by loss of target cell integrity and release of chromium. In addition, selective deposition of PFP was seen at the interaction site of the target cell compared to other target cell regions. Collectively, these results are consistent with the exocytosis model and further support the hypothesis that PFP is one of the secreted moieties involved in NK cellular cytotoxicity. PMID- 1431559 TI - Liposomes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE) are excellent adjuvants for induction of an immune response to protein and tumor antigens. AB - Liposomes containing the synthetic lipophilic analog of muramyl dipeptide, muramyl tripeptide phosphatidylethanolamine (MTP-PE), were used as adjuvants for the induction of humoral and cellular immune responses following immunization with protein or tumor antigens. Cellular immune reactions, including delayed-type hypersensitivity and lymphoproliferation in vitro, were observed following immunization of mice with a mixture of antigen and liposome-MTP-PE. Immunization with murine melanoma K1735 cells, admixed with liposomal MTP-PE, induced a protective immune response as demonstrated by the rejection of transplanted tumor cells. Antibody production was also induced following immunization with protein antigens admixed with liposome-MTP-PE. The efficacy of adjuvant activity following immunization with antigens admixed with liposome-MTP-PE was equal to or better than that of complete Freund's adjuvant (CFA). Moreover, liposome-MTP-PE did not have the toxic side effects associated with CFA. These data suggest that phospholipid liposomes containing MTP-PE are superior adjuvants and should receive consideration for vaccine therapy. PMID- 1431560 TI - Actin polymerization contributes to neutrophil chemotactic dysfunction following thermal injury. AB - The agent(s) and mechanism(s) responsible for suppression of neutrophil chemotaxis in association with major thermal injury have not been identified. We have proposed that the reduced random motility characterizing patients' cells may contribute to their generalized chemotactic dysfunction. Here we report that actin polymerization may be responsible for the loss of neutrophil motility associated with major thermal injury. Using a fluorescent ligand specific for polymerized or filamentous actin (NBD-phallacidin) in conjunction with flow cytometry, we have discovered that peripheral blood and exudate neutrophils from patients with major thermal injury contain increased levels of actin in a stably polymerized form. Because cyclic polymerization and depolymerization of actin is essential to cell motility, we suggest that actin polymerization may contribute in a major way to the attenuation of neutrophil random and chemotactic functions induced by major thermal injury. PMID- 1431561 TI - Infusion of zymosan-activated plasma affects neutrophils in peripheral blood and bone marrow in sheep. AB - Intravenous infusion of zymosan-activated plasma (ZAP) in sheep results in acute lung injury mediated in part by free radical release from stimulated neutrophils that are retained in increased numbers in the pulmonary microcirculation. ZAP infusion is also associated with long-term reduction in elicited superoxide anion generation from segmented neutrophils in the circulating and bone marrow pools for at least 24 h after the infusion. The purpose of our study was to investigate the effect of ZAP infusion on leukocyte counts and neutrophil granule-associated enzyme activity in the circulating and bone marrow pools. Cytochemical methods were used to characterize enzyme activity in primary granules (acid phosphatase and myeloperoxidase) and secondary granules (alkaline phosphatase). During the infusion period, neutrophil differential counts decreased less in venous blood than in matched arterial blood. Release from bone marrow stores was evident as increased numbers of circulating band neutrophils during and after the infusion. Neutrophils in venous and arterial blood smears were degranulated acutely during and 1-3 h after the infusion was stopped. Band and segmented neutrophils in bone marrow also appeared slightly degranulated 1-2 h after the infusion. In vitro experiments showed that band and segmented neutrophils in bone marrow degranulated in response to ZAP incubation. Immature polymorphonuclear leukocytes did not degranulate. Five to 24 h after ZAP infusion, enzyme activity in circulating and bone marrow neutrophils was at baseline levels, suggesting that new cells were being released into the circulating pool because degranulated neutrophils do not synthesize new granules. Another indication of a long-term effect in bone marrow were slight decreases in the percentage of immature polymorphonuclear leukocytes and band neutrophils and a significant decrease in the percentage of eosinophils, all of which coincided with a significant increase in the percentage of segmented neutrophils. Our results demonstrate that circulating complement anaphylatoxins affect neutrophils in bone marrow as well as the vascular space. PMID- 1431562 TI - Ontogenic development of macrophage subpopulations and Ia-positive dendritic cells in fetal and neonatal rat spleen. AB - Development, differentiation, and distribution of macrophage subpopulations and Ia+ dendritic cells in the fetal and neonatal rat spleen were investigated by means of double immunohistochemical staining and immunoelectron microscopy. To characterize these cell populations, a panel of anti-rat macrophage monoclonal antibodies (RM-1, ED2, ED3, TRPM-3, Ki-M2R) and an anti-rat Ia antibody (OX6) were used. In the fetal rat spleen, macrophages were first detected by RM-1 at fetal day 15. ED2+ and/or Ki-M2R+ macrophages appeared at fetal day 16. TRPM-3+ and/or ED3+ macrophages appeared a day later. During the fetal and neonatal development, ED2+ and TRPM-3+ macrophages differentiated independently, maturing into red pulp macrophages and marginal metallophilic and marginal zone macrophages respectively. Intimate topographical relations were observed between ED2+ macrophages and hematopoietic cells and between TRPM-3+ macrophages and marginal zone lymphocytes. Ia+ cells were first observed around arterioles at fetal day 15. In the fetal and neonatal period, the number of Ia+ cells gradually increased, their shape became dendritic, and they matured into interdigitating cells in the inner periarteriolar lymphatic sheath. In ontogeny, Ia+ dendritic cells were not stained with ED2 or TRPM-3. These results suggest that ED2+ macrophages, TRPM-3+ macrophages, and Ia+ dendritic cells are distinct cell lines that pursue independent developmental process in spleen ontogeny. PMID- 1431563 TI - Monocyte diapedesis through an in vitro vessel wall construct: inhibition with monoclonal antibodies to thrombospondin. AB - Human peripheral blood monocytes were examined for migration across an endothelial cell monolayer in an in vitro vessel wall construct. Few monocytes invaded in the absence of a chemotactic gradient, despite significant adhesion to the endothelial monolayer. However, the addition of zymosan-activated human plasma to the lower compartment, to create a chemotactic gradient across the vessel wall, resulted in significantly enhanced monocyte migration. Pretreatment of the monocytes with monoclonal antibodies to thrombospondin (TSP) dramatically inhibited monocyte diapedesis into the vessel wall. The same treatment inhibited monocyte adhesion to endothelial cells in two-dimensional monolayer cultures as well as in vessel wall constructs (no chemotactic gradient). Of interest, however, the monoclonal antibodies had no inhibitory effect on monocyte migration into collagen gels devoid of endothelial cells in response to the same chemotactic gradient, suggesting the importance of TSP in monocyte-endothelial cell interactions. Monoclonal antibodies to fibronectin and normal mouse immunoglobulin G did not inhibit migration in this model of a vessel wall. Furthermore, monoclonal antibodies to TSP showed no inhibition of human peripheral blood neutrophil migration. Previous studies have shown that monocytes synthesize TSP and express this moiety on their surface. The present data suggest that monocytes may utilize TSP to interact with endothelial cells lining the vessel wall during diapedesis. PMID- 1431564 TI - Activation of human monocyte chemiluminescence response by acylpoly(1,3)galactosides derived from Klebsiella pneumoniae. AB - The stimulating activity of several preparations isolated from a membrane proteoglycan of a nonencapsulated smooth strain of Klebsiella pneumoniae (Kp-MPG) on the oxidative burst of human blood monocytes was assessed by luminol-enhanced chemiluminescence (CL). Five Kp derivatives were studied: a 34-kd acylpoly(1,3)galactoside (APG), obtained by drastic alkaline hydrolysis and purified by chromatography; an APG preparation subjected to acid hydrolysis that removed the core part and all fatty acids, leaving intact the galactose chain of APG (GC-APG); an APG preparation subjected to mild oxidation (ox APG); a preparation obtained by mild alkaline hydrolysis of Kp-MPG, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and a polymer of the latter compound, APG pol. EFA-APG directly stimulated monocyte CL, whereas Kp-MPG, APG pol, and the whole bacterial cells had little or no activity. APG itself and ox APG induced a weaker response than EFA-APG. Polymyxin B sulfate completely inhibited the CL response to bacterial lipopolysaccharide (LPS) but not to EFA-APG. The stimulating action of EFA-APG on blood monocytes was dependent on the extracellular levels of both calcium and magnesium. Preincubation of monocytes with monoclonal antibody anti-Mac-1 directed against CD11b, the alpha chain of complement receptor type 3 (CR3; CD11b/CD18), strongly inhibited CL activation by EFA-APG and to a lesser extent CL activation by unopsonized zymosan and rough LPS. Altogether, these findings provide indirect evidence for the contribution of the CD11b/CD18 integrin in the functional interaction of EFA-APG with monocyte membranes. They demonstrate the role of fatty acids in the triggering of monocyte oxidative burst, while the polysaccharide chain itself does not contribute to induction of the CL response in this model. In keeping with the effects of EFA-APG and APG, we show that the monocyte CL response was triggered by bacterial LPS from the rough strain of Salmonella minnesota Re 595 and its lipid A, but not by LPS from smooth strains, again suggesting a critical role for the lipid moiety. PMID- 1431566 TI - Augmented expression and release of nonspecific cross-reacting antigens (NCAs), members of the CEA family, by human neutrophils during cell activation. AB - Nonspecific cross-reacting antigens (NCAs) are a group of human glycoproteins immunologically cross-reactive with carcinoembryonic antigen (CEA). Our previous studies have shown that at least seven NCA glycoproteins different in molecular weight and antigenic reactivity, including a species corresponding to CD67, can be detected in neutrophil granulocytes. In the present paper, it is demonstrated that neutrophil activation induced with soluble stimulators, the calcium ionophore A23187, N-formylmethionyl-leucyl-phenylalanine, and phorbol myristate acetate, results in augmented release and cell surface expression of NCAs. The NCA release was correlated with the discharge of azurophil granules but not with that of specific granules and was attributable to the release of NCA species of 53 and 30 kd. The increased NCA expression on the cell surface was due to increments of the NCAs of 160, 100 (CD67), 95, 90, 30, and 26 kd. These results, together with the previous findings that the CEA family members can mediate intercellular adhesion and bind Escherichia coli in vitro, imply that the neutrophil NCAs participate in the functions of neutrophils such as phagocytosis, chemotaxis, and adherence. PMID- 1431565 TI - Isolation and characterization of macrophages from rat embryonic muscle culture. AB - We have previously described the wide distribution of resident macrophages in normal rat skeletal muscle. In this study, we investigated the characteristics of the macrophages that occur in rat embryo muscle cultures. We showed that cells of monocyte-macrophage lineage are present in primary muscle cultures of rat embryos (18 days in gestation) and that these cells form morphologically and phenotypically heterogeneous populations, based on their reaction with monoclonal antibodies ED1, ED2, ED3, and OX43. Constitutively Ia+ cells with dendritic appearance were also observed. Furthermore, we established the procedure for isolation of macrophages from the primary muscle cultures. The isolated cells, mostly ED1+, expressed class I and CD4 antigens and bore complement (C3) receptors on their surfaces. The fact that cell of monocyte-macrophage lineage occur in the embryonic muscle suggests that during embryogenesis these cells may enter the developing muscle and give rise to a population of tissue-associated macrophages. PMID- 1431567 TI - Activation of bovine neutrophils by Pasteurella haemolytica leukotoxin is calcium dependent. AB - In this study, we used the fluorescent probe Fluo-3 to show that an increase in cytosolic free calcium, [Ca2+]i, occurred when suspensions of bovine neutrophils were incubated with sublethal concentrations of P. haemolytica leukotoxin. This increase in [Ca2+]i was dependent on the concentration of leukotoxin present in the medium and, at a given concentration of leukotoxin, dependent on the external calcium concentration. The calcium channel blocker verapamil and the beta adrenergic antagonist propranolol inhibited leukotoxin-stimulated Ca2+ gain, as did a neutralizing antileukotoxin monoclonal antibody. As reported previously, incubation of bovine neutrophils with partially purified leukotoxin stimulated a vigorous luminol-dependent chemiluminescence response (LDCL). The present study shows that LDCL stimulation was dependent on the presence of extracellular calcium and was inhibited by the addition of verapamil and propranolol. These data indicate that bovine neutrophils exhibit a considerable increase in cytoplasmic free calcium when they are incubated with P. haemolytica leukotoxin in the presence of external calcium. They also provide evidence that an increased [Ca2+]i is required for functional activation of the bovine neutrophil oxidative burst by P. haemolytica leukotoxin. PMID- 1431568 TI - Cholesterol esterification rate in plasma depleted of very low and low density lipoproteins is controlled by the proportion of HDL2 and HDL3 subclasses: study in hypertensive and normal middle-aged and septuagenarian men. AB - The relationship between the fractional rate of cholesterol esterification (FERHDL) in very low density lipoprotein (VLDL)- and low density lipoprotein (LDL)-depleted plasma and the particle size distribution of high density lipoproteins (HDL) were studied in: a) a control group of 9 apparently healthy men (42 +/- 11 years); b) 15 septuagenarians (76 +/- 6 years) who had no clinical signs of coronary artery disease; and c) 32 outpatients with essential hypertension of different stages of severity (51 +/- 10 years). There were small differences between the groups with respect to their plasma total and HDL cholesterol and plasma triglyceride levels. However, there was a highly significant increase in FERHDL in patients with hypertension compared to control and older men. The HDL of hypertensive patients had a markedly increased relative content of HDL3b, while their HDL2b fraction was reduced by over 50% compared to the other groups. Overall, there was a strong positive correlation between FERHDL and HDL3b (r = 0.89; P less than 0.001) and a negative correlation between FERHDL and HDL2b (r = -0.61; P less than 0.001) and HDL3a (r = -0.77; P less than 0.001). These findings confirm our previous conclusions that FERHDL reflects the relative HDL subclass distribution. In addition, we demonstrate that FERHDL is increased in hypertensive male subjects regardless of the stage of hypertension, i.e., whether or not organic lesions have already become manifest (stage III and stages I plus II, respectively). PMID- 1431569 TI - Increased serum apoA-IV concentrations in experimental uremic rats. AB - Normal histochemical analysis localizes apoA-IV within renal proximal tubules, which suggests that the kidney is a major catabolic site. In clinical renal failure and animal models of decreased renal function, low molecular weight proteins cannot be efficiently filtered through the glomerular basement membrane, and therefore they accumulate in plasma. In normal plasma, apoA-IV exists as both lipoprotein associated and lipoprotein-free, low molecular weight forms. To examine this further, uremic serum apolipoprotein and mRNA levels were examined in surgically 5/6 nephrectomized rats. Compared to sham-operated controls, uremic serum apoA-IV was elevated twofold and was distributed to a greater extent in the lipoprotein-free subfraction. Serum triglycerides were unchanged. Despite finding no correlation between serum apoA-IV and triglyceride levels (in either the d less than 1.006 g/ml or 1.006 less than d less than 1.019 g/ml fraction), serum apoA-IV was positively correlated with the renal function parameters of blood urea nitrogen (r = 0.949, P less than 0.001), creatinine (r = 0.952, P less than 0.001), and uric acid (r = 0.903, P less than 0.001). In addition, the concentration of apoA-IV per milligram of renal homogenate protein in uremic rats was significantly higher than that of control rats, whereas there was no difference in the content of apoA-I between the two groups. ApoA-I, apoA-IV, and apoB mRNA levels in hepatic and in intestinal tissue were undistinguishable between the uremic and surgical sham rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431570 TI - Thyroid hormone differentially augments biliary sterol secretion in the rat. I. The isolated-perfused liver model. AB - Thyroid hormone lowers serum cholesterol and alters sterol metabolic processes. This laboratory has previously reported increased biliary lipid secretion as an early effect of triiodothyronine (T3) in the rat. To evaluate whether the bile lipid action of T3 is a primary or secondary effect, the isolated-perfused rat liver model was used. Red blood cells in lipid-free buffer were used to perfuse livers of euthyroid and methimazole-hypothyroid rats, as well as hypothyroid rats given T3 at intervals before perfusion. Bile flow was maintained by taurocholate perfusion. Hypothyroid rats had elevated pre-perfusion serum cholesterol compared to euthyroid (107 +/- 4 vs. 65 +/- 2 mg/dl) and decreased biliary cholesterol (0.016 +/- 0.001 vs. 0.031 +/- 0.004 mumol/g liver/h) secretion. Serum cholesterol decreased to euthyroid levels by 18 h after T3, an effect that was prevented by bile duct ligation. Bile cholesterol secretion doubled by 18 h, and reached levels twice euthyroid by 42 h, while phospholipid secretion doubled to levels just above euthyroid. The fourfold increase in biliary cholesterol secretion occurred with lipid-free perfusion and unchanging bile acid uptake or output. It occurred without a fall in hepatic lipoprotein cholesterol secretion. Blockade of cholesterol synthesis with lovastatin failed to alter T3-augmented bile cholesterol secretion. We conclude that T3 induces biliary cholesterol secretion concomitantly with the fall in serum cholesterol. This augmented biliary secretion did not appear to depend upon lipoprotein uptake, increased bile acid transport, or cholesterol synthesis. It did not occur at the expense of hepatic lipoprotein secretion. Facilitated biliary lipid secretion may be a primary effect of T3. PMID- 1431571 TI - Thyroid hormone differentially augments biliary sterol secretion in the rat. II. The chronic bile fistula model. AB - To further define thyroid hormone effects on bile acid synthesis and biliary lipid secretion, studies were done in chronic bile fistula rats. Euthyroid and methimazole-hypothyroid rats, with and without triiodothyronine (T3) injection, had total bile diversion for timed bile collections. With interrupted enterohepatic circulation, cholesterol absorption is negligible and bile acid secretion equals bile acid synthesis rate. Hypothyroid rats had diminished levels of bile acid synthesis and biliary secretion of cholesterol and phospholipid. Single dose T3 injection produced a 13-fold increase in bile cholesterol secretion and a 3-fold increase in phospholipid secretion, both initiated 12 h after T3. Bile acid synthesis increased by 50%, but the increase did not begin until 24 h after T3. Neither hypothyroidism nor T3 treatment abolished diurnal rhythms of bile acid synthesis and biliary lipid secretion. Inhibition of cholesterol synthesis with lovastatin resulted in a persistent 33% decrease in bile acid synthesis in euthyroid and hypothyroid rats, while bile cholesterol secretion only transiently decreased. Inhibition of cholesterol synthesis did not alter T3-induced bile cholesterol secretion, with a 10-fold increase seen. However, bile acid synthesis was not stimulated by T3 in the presence of lovastatin. We conclude that facilitated bile acid synthesis and biliary cholesterol secretion are early effects of T3 and may account for the hypocholesterolemia of T3. Cholesterol synthesis does not appear to be required for the T3-induced bile cholesterol secretion. PMID- 1431572 TI - Role of the intestinal acyl-CoA:cholesterol acyltransferase activity in the hyperresponse of diabetic rats to dietary cholesterol. AB - Contrary to normal rats, diabetic rats are known to develop marked hypercholesterolemia when fed a cholesterol-enriched diet. The triggering factor involved in this hyperresponse has not been identified. With the aim of clarifying the role of the intestinal acyl-CoA:cholesterol acyltransferase (ACAT), we studied the effects of a high fat diet and the changes of intestinal ACAT activity during the early development of streptozotocin-diabetes in rats. Feeding diabetic rats with a diet enriched in cholesterol and saturated fat produced an increase in plasma and in tissue cholesterol as early as 3 days after streptozotocin injection in the absence of hyperphagia. Under these experimental conditions, treatment with insulin or with the ACAT inhibitor CL-277082 significantly reduced the plasma cholesterol to levels measured in nondiabetic rats fed the same high fat diet. An increase in [14C]cholesterol in plasma very low density lipoprotein was observed after oral administration of labeled cholesterol to 3-day diabetic rats. In parallel experiments, the direct measurement of small intestine microsomal ACAT activity revealed an increase, averaging 288% in diabetic rats 3 days after diabetes induction. This change in ACAT activity occurred simultaneously with an increase in plasma glucagon and was normalized by insulin treatment. The induction of intestinal ACAT activity in diabetic rats, its modulation by insulin, and the hypocholesterolemic effects of insulin or CL-277082 treatment clearly indicate that ACAT activity plays a major role in the initiation of diabetes-associated hypercholesterolemia. PMID- 1431573 TI - Distribution of phosphatidylcholine molecular species between mixed micelles and phospholipid-cholesterol vesicles in human gallbladder bile: dependence on acyl chain length and unsaturation. AB - The partitioning of phosphatidylcholine (PC) molecular species between mixed micelles and vesicles was studied in each of seven human gallbladder biles. Biles were fractionated by Sephacryl S-300 SF gel filtration chromatography, and PC species in the micellar and vesicular fractions were quantitated by high performance liquid chromatography. Micelles were enriched in species containing unsaturated acyl groups (e.g., 16:1-18:2, 18:1-18:2, and 18:1-18:3); vesicles were enriched in more highly saturated species (e.g., 16:0-16:1, 16:0-18:1, and 18:0-18:1). Separate multivariate analyses for each bile demonstrated that the distribution of PC species between vesicles and micelles was related to the degree of sn-1 and sn-2 unsaturation, and sn-1, but not sn-2, chain length. In addition, the tendency to partition into the micellar phase was particularly marked when unsaturation was present at both the sn-1 and sn-2 positions. When this interaction was included in the multivariate analyses, the regression models accounted for virtually all of the variation in PC partitioning (for each of the seven patients r2 = 0.92-0.98, P less than 0.03). These results suggest that the partitioning of PC species between micelles and vesicles is strictly determined by sn-1 chain length and the degree of unsaturation at both the sn-1 and sn-2 positions. In light of recent reports that fatty acyl composition influences the cholesterol content of vesicles and micelles in model biles, these results raise the possibility that diet-induced alterations in the phospholipid species and the relative proportions of biliary lipid particles may influence the cholesterol carrying capacity of bile. PMID- 1431574 TI - Effect of dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans. AB - Serum lipoprotein[a] (Lp[a]) is a strong risk factor for coronary heart disease. We therefore examined the effect of dietary fatty acid composition on serum Lp[a] levels in three strictly controlled experiments with healthy normocholesterolemic men and women. In Expt. I, 58 subjects consumed a control diet high in saturated fatty acids for 17 days. For the next 36 days, 6.5% of total energy intake from saturated fatty acids was replaced by monounsaturates plus polyunsaturates (monounsaturated fatty acid diet; n = 29) or by polyunsaturates alone (polyunsaturated fatty acid diet; n = 29). Both diets caused a slight, nonsignificant, increase in median Lp[a] levels, with no difference between diets. In Expt. II, 10% of energy from the cholesterol-raising saturated fatty acids (lauric, myristic, and palmitic acid) was replaced by oleic acid or by trans-monounsaturated fatty acids. Each of the 59 participants received each diet for 3 weeks in random order. The median level of Lp[a] was 26 mg/l on the saturated fatty acid diet; it increased to 32 mg/l (P less than 0.020) on the oleic acid diet and to 45 mg/l (P less than 0.001) on the trans-fatty acid diet. The difference in Lp[a] between the trans-fatty acid and the oleic acid diets was also highly significant (P less than 0.001). Expt. III involved 56 subjects; all received 8% of energy from stearic acid, from linoleic acid, or from trans monounsaturates, for 3 weeks each. All other nutrients were equal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431575 TI - Inhibitors of sterol synthesis. Chemical synthesis and spectral properties of 3 beta-hydroxy-5 alpha-cholesta-8(14),24-dien-15-one, 3 beta,25-dihydroxy-5 alpha cholest-8(14)-en-15-one, and 3 beta,24-dihydroxy-5 alpha-cholest-8(14)-en-15-one and their effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells. AB - Side-chain functionalized delta 8(14)-15-ketosterols have been synthesized from 3 beta-acetoxy-24-hydroxy-5 alpha-chol-8(14)-en-15-one (VI) as part of a program to prepare potential metabolites and analogs of 3 beta-hydroxy-5 alpha-cholest-8(14) en-15-one (I), a potent regulator of cholesterol metabolism. Oxidation of VI to the 24-aldehyde VII, followed by Wittig olefination with isopropyltriphenylphosphonium iodide gave 3 beta-acetoxy-5 alpha-cholesta 8(14),24-dien-15-one (VIII), which was hydrolyzed to the free sterol IX. Oxymercuration of VIII followed by hydrolysis of the 3 beta-acetate gave 3 beta,25-dihydroxy-5 alpha-cholest-8(14)-en-15-one (IV). Hydroboration-oxidation of VIII followed by hydrolysis of the 3 beta-acetate gave 3 beta,24-dihydroxy-5 alpha-cholest-8(14)-en-15-one (V) as a 5:4 mixture of the 24R and 24S epimers. 1H and 13C nuclear magnetic resonance (NMR) assignments and mass spectral fragmentation patterns, supported by high-resolution measurements, are presented for IV and its 3 beta-acetate, V, VII, VIII, and IX. Characterization of IV by NMR and of trimethylsilyl ethers of IV and V by gas chromatography-mass spectrometry was compatible with spectral data for samples of IV and V isolated previously after incubation of I with rat liver mitochondria in the presence of NADPH. Sterols IV, V, and IX were very potent in lowering of the level of 3 hydroxy-3-methylglutaryl coenzyme A reductase activity in Chinese hamster ovary cells; their potency was comparable to that of I. PMID- 1431576 TI - Hepatic apolipoprotein J is secreted as a lipoprotein. AB - Apolipoprotein J (apoJ) is a unique glycoprotein thought to be involved in a variety of physiological processes, including lipid transport, regulation of complement function, sperm maturation, programmed cell death, and membrane recycling. In the plasma, apoJ is associated with apoA-I in high and very high density lipoproteins. In this report we demonstrate that HepG2 human hepatocellular carcinoma cells secrete apoJ in association with a significant amount of lipid, providing unequivocal evidence that apoJ can transport lipids. The HepG2 cell line has provided important clues about the structural organization of nascent lipoprotein particles. HepG2 cell apoJ-containing lipoproteins are dense and heterogenous in size, ranging from 100 to 910 kDa. Plasma and HepG2 cell apoJ-lipoproteins differ in size distribution. Both have alpha 2 electrophoretic mobility, although their average mobilities differ within the alpha 2 region. In contrast to plasma apoJ-HDL which contain little triglyceride and which can associate with apoA-I, HepG2 cell apoJ-lipoproteins are rich in triglyceride and lack apoA-I. By implication, nascent apoJ lipoproteins undergo plasma remodeling that results in triglyceride depletion and apoA-I association. We propose that the metabolic consequences of this remodeling play an important role in lipid homeostasis in localized tissue environments, particularly where organs are isolated from the blood by cellular barriers such as in testis and brain. In such tissues, apoJ is expressed constitutively in high level compared to other lipid transport proteins. PMID- 1431577 TI - Physiologic mechanisms for reduced apolipoprotein A-I concentrations associated with low levels of high density lipoprotein cholesterol in patients with normal plasma lipids. AB - Low plasma concentrations of high density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apoA-I) are major risk factors for coronary heart disease (CHD). Low HDL levels are common in patients with hypertriglyceridemia, but they also occur in those with normal plasma lipids; the latter include obese patients and cigarette smokers, though other patients with low HDL levels are neither obese nor smokers. The present study was designed to define metabolic causes of low apoA-I levels in normal-weight, normolipidemic patients. ApoA-I tracer studies were carried out in two groups of normolipidemic patients having low HDL levels to determine input rates and residence times for ApoA-I; these patients included 11 nonobese nonsmokers and 11 nonobese cigarette smokers. Their results were compared to those of 20 normal-weight, normolipidemic controls with normal HDL levels and 12 obese nonsmokers also having low HDL. In all three groups manifesting low HDL-cholesterol and low apoA-I levels, residence times for plasma apoA-I were reduced by approximately 30%, compared to control subjects with normal HDL levels. In contrast, average input rates for apoA-I were similar among the three low-HDL patients and control subjects. No differences in apoA-I kinetics were observed among any of the three groups with low apoA-I concentrations. Within each of the four groups of the study, however, input rates for apoA-I were highly correlated with plasma concentrations of apoA-I. Thus, for individuals with normal levels of plasma lipids, both residence times and input rates for apoA-I appeared to be important determinants of apoA-I levels. Residence times for apoA-I were reduced in almost all patients with low apoA-I levels, regardless of concomitant factors, whereas input rates were highly variable among individuals. PMID- 1431578 TI - Protocol for the study of the metabolism of retinyl esters in plasma lipoproteins during postprandial lipemia. AB - An efficient protocol is described for the study of the kinetics of retinyl esters in whole plasma and several lipoprotein fractions following the consumption of an oral fat load containing vitamin A (retinol). To allow for a more complete characterization of the kinetics of retinyl esters in different lipoprotein fractions, a simplified two-step ultracentrifugation procedure is reported for the efficient and reproducible isolation of triglyceride-rich chylomicrons from nonfasting subjects, VLDL-sized lipoprotein particles, and the triglyceride-poor lipoprotein fraction. The present method for the determination of retinyl esters is based on the direct application of the lipid fraction onto a normal phase HPLC column without requiring the lipid extract to be desiccated and resolubilized. All of the commonly occurring esters of retinol elute as a single peak with a retention time of 1.6-1.8 min followed by retinyl acetate (serving as the internal standard) and retinol with retention times of 2-2.5 min and 5-5.5 min, respectively. With this system, a new sample can be processed every 10 min and a complete set of 60 samples from a typical oral fat load can analyzed in one working day with minimal technical interaction. By normalizing to the area under the internal standard to correct for variability in the injected volume, the coefficient of variability for the concentration retinyl esters within a single run is less than 5% and less than 10% between runs. PMID- 1431579 TI - Cryopreservation with sucrose maintains normal physical and biological properties of human plasma low density lipoproteins. AB - The ability to preserve low density lipoprotein (LDL) preparations frozen for weeks and months without changes in structure or biological properties is of potential use in long-term comparative studies of LDL. We demonstrate that freeze thawing of LDL causes marked alterations in its structure and biological behavior, and that such changes can be prevented by the addition of sucrose to the LDL solution prior to freezing. Freezing LDL at -70 degrees C in the absence of sucrose resulted in aggregation and fusion of particles as measured by electron microscopy, spectrophotometric absorption, and column gel filtration. This was associated with increased binding affinity of monoclonal antibodies at epitopes distant from the receptor binding region. Functional changes induced by freezing included 3- to 10-fold increases in binding at 4 degrees C and 37 degrees C, and uptake of LDL in fibroblasts, attributable mainly to increases in nonspecific binding processes. Cryopreservation of LDL in 10% sucrose (w/v) completely prevented the structural and functional changes incurred after short term freezing, and LDL cryopreserved in sucrose for as long as 18 months displayed cell binding, uptake, and degradation very similar to that of freshly obtained LDL. PMID- 1431580 TI - Apolipoprotein B(Arg3500----Gln) allele specific polymerase chain reaction: large scale screening of pooled blood samples. AB - A two-step polymerase chain reaction (PCR) method for the rapid detection of the apolipoprotein B(Arg3500----Gln) mutation in a mixture of pooled blood samples is described. In the first step PCR, a short gene fragment surrounding codon 3500 is amplified. Subsequently the reaction product is subjected to a second amplification in which a mutation-specific primer is used. A PCR product is generated only if the mutant sequence is present in the DNA pool. Individuals carrying the mutation can then be identified by PCR with mutagenic primers and MspI restriction typing, essentially as described by Hansen et al. (J. Lipid Res. 1991. 32: 1229-1233). PMID- 1431581 TI - Cholesteryl ester storage disease: complex molecular effects of chronic lovastatin therapy. AB - To better characterize the in vivo effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition on human lipid metabolism, an adolescent male with cholesteryl ester storage disease (CESD) was treated chronically with lovastatin. Therapy was associated with decreased liver-spleen size, improved but not normal serum lipids, a 26% decrease in hepatic cholesteryl ester, a 12% decrease in unesterified hepatic cholesterol, and a fourfold increase in hepatic low density lipoprotein (LDL) receptor protein. Hepatic mRNA levels for the LDL receptor and apolipoprotein (apo) B standardized to levels of hepatic gamma actin mRNA were unchanged with therapy. Kinetic studies revealed no change in the LDL fractional catabolic rate and a decrease in the LDL production rate. Size exclusion chromatography showed striking reductions in plasma very low density lipoprotein (VLDL) cholesterol and intermediate density lipoprotein (LDL) cholesterol but not LDL cholesterol with therapy. Mean LDL particle size and the LDL particle size range were increased by treatment. However, there was no difference in the ability of pretreatment or treatment LDL to bind to the LDL receptor on cultured cells consistent with previous studies in animals, indicating that lovastatin may alter LDL particles to impair interaction with the LDL receptor in vivo but not in vitro. Lovastatin therapy in CESD appears to be clinically beneficial and has complex effects on lipid metabolism that may include a dominant inhibitory effect on hepatic lipoprotein production, posttranscriptionally mediated induction of the LDL receptor, and alterations of LDL particles that interfere with their clearance by the LDL receptor in vivo. PMID- 1431582 TI - Plasma lipoprotein lipid and Lp[a] changes with substitution of elaidic acid for oleic acid in the diet. AB - The effect of additional dietary trans fatty acids (7% energy) on plasma lipids was assessed in a double-blind comparison of four separate diets: 1, enriched with butter fat (lauric-myristic-palmitic); 2, oleic acid-rich; 3, elaidic acid rich; 4, palmitic acid-rich. The total dietary period was 11 weeks and comprised normal foods plus specific fat supplements. In 27 mildly hypercholesterolemic men, total and LDL cholesterol were significantly lower during the 3-week oleic acid-rich diet, and were similar during the other three diets. For the four diets LDL cholesterol levels were in mg/dl: 1, 163; 2, 151; 3, 165; 4, 161. HDL cholesterol was significantly higher with the palmitic acid-rich diet, 42 mg/dl, compared with elaidic acid, 38 mg/dl, which in turn was not lower than with oleic acid, 38 mg/dl. Plasma elaidic acid concentration rose seven-fold with the trans fatty acid diet but did not increase the vulnerability of LDL to oxidative change. The elaidic acid-rich diet led to significant elevations in the level of Lp[a] compared to all the other test diets. The Lp[a] level increased to 296 +/- 220 U/l in the elaidic acid-rich period from 235 +/- 182 (mean +/- SD) in the first ("butter") period (P less than 0.001) compared with 249 +/- 204 in the palmitic acid period (P less than 0.001) and 236 +/- 201 in the oleic acid period (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431583 TI - ApoB-75, a truncation of apolipoprotein B associated with familial hypobetalipoproteinemia: genetic and kinetic studies. AB - We have identified a mutation of apolipoprotein B (apoB) in a kindred with hypobetalipoproteinemia. Four affected members had plasma concentrations of total cholesterol of 115 +/- 14, low density lipoprotein (LDL)-C of 48 +/- 11, and apoB of 28 +/- 9 (mg/dl mean +/- SD). The values correspond to approximately 30% the values for unaffected relatives. Triglyceride and high density lipoprotein (HDL) C concentrations were 92 +/- 50 and 49 +/- 4, respectively, neither significantly different from unaffected relatives. Western blots of plasma apoB of affected subjects showed two major bands: apoB-100 and an apoB-75 (mol wt of approximately 418,000). DNA sequencing of the appropriate polymerase chain reaction (PCR) amplified genomic DNA segment revealed a deletion of the cytidine at nucleotide position 10366, resulting in a premature stop codon at amino acid residue 3387. In apoB-75/apoB-100 heterozygotes, two LDL populations containing either apoB-75 or apoB-100 could be distinguished from each other by gel permeation chromatography and by immunoblotting of nondenaturing gels using monoclonal antibodies B1B3 (epitope between apoB amino acid residues 3506-3635) and C1.4 (epitope between residues 97-526). ApoB-75 LDL were smaller and more dense than apoB-100 LDL. To determine whether the low concentration of apoB-75 was due to its enhanced LDL-receptor-mediated removal, apoB-75 LDL were isolated from the proband's d 1.063-1.090 g/ml fraction (which contained most of the apoB-75 in his plasma) by chromatography on anti-apoB and anti-apoA-I immunoaffinity columns. The resulting pure apoB-75 LDL fraction interacted with the cells 1.5-fold more effectively than apoB-100 LDL (d 1.019-1.063 g/ml). To determine the physiologic mechanism responsible for the hypobetalipoproteinemia, in vivo kinetic studies were performed in two affected subjects, using endogenous labeling of apoB-75 and apoB-100 with [13C]leucine followed by multicompartmental kinetic analyses. Fractional catabolic rates of apoB-75 VLDL and LDL were 2- and 1.3-fold those of apoB-100 very low density lipoprotein (VLDL) and LDL, respectively. Production rates of apoB-75 were approximately 30% of those for apoB-100. This differs from the behavior of apoB-89, a previously described variant, whose FCRs were also increased approximately 1.5-fold relative to apoB-100, but whose production rates were nearly identical to those of apoB-100. Thus, in contrast to the apoB-89 mutation, the apoB-75 mutation imparts two physiologic defects to apoB-75 lipoproteins that account for the hypobetalipoproteinemia, diminished production and increased catabolism. PMID- 1431584 TI - Chemiluminescent simultaneous determination of phosphatidylcholine hydroperoxide and phosphatidylethanolamine hydroperoxide in the liver and brain of the rat. AB - The quantification of phospholipid hydroperoxides in biological tissues is important in order to know the degree of peroxidative damage of membrane lipids. For this purpose, optimal conditions for the chemiluminescent simultaneous assay of phosphatidylcholine hydroperoxide (PCOOH) and phosphatidylethanolamine hydroperoxide (PEOOH) in rat liver and brain were determined. A chemiluminescence detection-high performance liquid chromatography (CL-HPLC) method that incorporates cytochrome c and luminol as a post-column hydroperoxide-specific luminescent reagent was used (Miyazawa et al. 1987. Anal. Lett. 20: 915-925; Miyazawa. 1989. Free Radical Biol. Med. 7: 209-217). An n-propylamine-bound silica column with hexane-2-propanol-methanol-water 5:7:2:1 (v/v/v/v) (flow rate 1.0 ml/min) as eluant was used to determine both PCOOH and PEOOH, which were separated from each other and from other lipids and lipid-soluble antioxidants. High reproducibility and sensitivity as low as 10 pmol hydroperoxide-O2 were observed with a mixture of 10 micrograms/ml cytochrome c and 2 micrograms/ml luminol in 50 mM borate buffer (pH 10.0, flow rate 1.1 ml/min) as luminescent reagent and a post-column mixing joint temperature of 40 degrees C. Using the established analytical conditions, it was confirmed that both PCOOH (1324 +/- 122 pmol/g liver, 114 +/- 18 pmol/g brain, mean +/- SD) and PEOOH (728 +/- 89 pmol/g liver, 349 +/- 60 pmol/g brain, mean +/- SD) are present in the liver and brain of Sprague-Dawley rats bred on a slightly modified AIN-76A semisynthetic diet for 3 months. The phospholipid hydroperoxide content in the rat liver was shown to be affected by dietary oils, but not significantly affected in the brain. PMID- 1431585 TI - Improved preparation method for lysogangliosides. AB - Lyso-GM3 and -GM1 gangliosides were prepared from the corresponding N,N' dideacylated gangliosides using N-trifluoroacetylation at the sphingosine moiety, followed by N-acetylation and mild saponification. The blocking reaction was performed using a water-ether bilayer system at alkaline medium, in which the N trifluoroacetylation occurred predominantly at the lipid moiety. Through the procedure, lysoGM3 and lysoGM1 were obtained with higher yields from the corresponding dideacylated gangliosides than through the previous method using 9 fluorenylmethoxycarbonyl chloride as a blocking group or of direct N-acetylation of it on liposomes containing starting ganglioside and other lipid. Chemical structures of the lysogangliosides and the synthetic intermediates were confirmed by the proton nuclear magnetic resonance spectrometry and negative fast atom bombardment-mass spectrometry. PMID- 1431586 TI - A simple and rapid method for the preparation of apolipoproteins for electrophoresis. AB - A new method is described for the rapid preparation of apolipoproteins for polyacrylamide gel electrophoresis. It is suitable for all serum lipoproteins including chylomicrons. The procedure involves extraction with diethyl ether in the presence of trichloroacetic acid and sodium deoxycholate. The method gives an improved protein recovery, in particular with chylomicrons. In addition, samples do not require dialysis to remove salts (e.g., KBr) prior to processing; as a consequence, the procedure requires only 1 h. Due to this rapidity and the high yields, the procedure is superior to present methods utilizing ethanol-diethyl ether extraction. PMID- 1431588 TI - Computational sequence analysis revisited: new databases, software tools, and the research opportunities they engender. AB - The increasing quantity and complexity of sequences and structural data for proteins and nucleic acids create both problems and opportunities for biomedical researchers. Fortunately, a new generation of practical computer tools for data analysis and integrated information retrieval is emerging. Recent developments in fast database searching, multiple sequence alignment, and molecular modeling are discussed and windows-based, mouse-driven software for CD-ROM and network information retrieval are described. Each method is illustrated with a practical example pertinent to lipid research. In particular, the connection among cholesteryl ester transfer protein, bactericidal permeability-increasing protein, and lipopolysaccharide-binding proteins is determined; novel repetitive sequence motifs in mammalian farnesyltransferase subunits and related yeast prenyltransferases are derived; biochemical insights from a three-dimensional model of human apolipoprotein D based on two insect lipocalins are discussed; the relationship between apolipoprotein D and gross cystic disease fluid protein from human breast is reviewed; and prospects for modeling apolipoprotein E-related proteins are described. In addition, information on a number of general and special-purpose sequence, motif, and structural databases is included. PMID- 1431587 TI - Sitosterolemia. AB - Sitosterolemia is a rare inherited lipid storage disease characterized chemically by the accumulation of plant sterols and 5 alpha-saturated stanols in plasma and tissues. Very low cholesterol synthesis due to a deficiency of HMG-CoA reductase associated with increased intestinal plant sterol absorption and slow hepatic sterol removal are major biochemical features. Because cholesterol synthesis cannot up-regulate, bile acid malabsorption mobilizes body sterols for bile acid synthesis and dramatically lowers plasma and monocyte sterol concentrations and may halt the progression of the atherosclerotic process. PMID- 1431589 TI - Lipoprotein lipase in plasma after an oral fat load: relation to free fatty acids. AB - Lipoprotein lipase (LPL) releases fatty acids from triglyceride-rich lipoproteins for use in cellular metabolic reactions. How this hydrolysis, which occurs at the vascular endothelium, is regulated is poorly understood. A fatty acid feedback system has been proposed by which accumulation of fatty acids impedes LPL catalyzed hydrolysis and dissociates the enzyme from its endothelial binding sites. We examined this hypothesis in humans who were subjected to an oral fat tolerance test of a mixed-meal type. Plasma triglycerides, free fatty acids, and LPL activity were measured before and repeatedly during a 12-h period after intake of the fat load. Since soybean oil with a high content of linoleic fatty acid was the source of triglycerides, a distinction could be made between endogenous free fatty acids (FFA) and FFA derived directly from lipolysis of postprandial triglyceride-rich lipoproteins. Mean LPL activity was almost doubled (P less than 0.01) 6 h after intake of the oral fat load. The rise in LPL activity was accompanied by an increase of plasma triglycerides and linoleic free fatty acids (18:2 FFA), but not of total plasma FFA, which instead displayed a heterogeneous pattern with essentially unchanged mean levels. The postprandial response of LPL activity largely paralleled the postprandial responses of 18:2 FFA and triglycerides. The highest degree of parallelism was seen between postprandial 18:2 FFA and LPL activity levels. Furthermore, the integrated response (area under the curve, AUC) for plasma measurements of LPL correlated with the AUC for 18:2 FFA (r = 0.40, P less than 0.05), but not with the AUC for plasma triglycerides (r = 0.21, ns). The high degree of parallelism and significant correlation between postprandial plasma LPL activity and 18:2 FFA support the hypothesis of fatty acid control of endothelial LPL during physiological conditions in humans. PMID- 1431590 TI - Calcium binding to phospholipid: structural study of calcium glycerophosphate. AB - To consider possible interaction of the phospholipid membrane with calcium ions, crystal structures of calcium dl-alpha- and beta-glycerophosphates (alpha- and beta-CaGs, respectively) were investigated by X-ray diffraction methods. After many attempts, relatively large single crystals of beta-CaG were prepared from the aqueous solution containing HCl, while crystals of CaHPO4.2H2O were obtained from alpha-CaG solution under the same crystallization conditions. The crystal structure of beta-CaG is orthorhombic with space group Pna2(1) and cell dimensions of a = 8.251(1), b = 13.038(3), c = 25.483 (10) A, V = 2741.5 (13) A3 and Z = 16 [four molecules (A to D) in an asymmetric unit]. Molecules of A to D took, as a whole, similar extended conformations, although A and B were different from C and D in the orientation about a glycerol C-C bond. Four independent beta glycerophosphates commonly act as two types of bidentate ligands, where one is the coordination to the calcium ion by the glycerol O(1) and phosphate O(22) atoms, and the other by the phosphate O(22) and O(23) atoms, thus forming the calcium coordination of a distorted square plane, respectively. Each of four independent calcium ions forms the same coordination geometry of a distorted pentagonal bipyramid. Infinite double layers consisting of alternate A/B molecules and of alternative C/D ones and sandwiching calcium ions were arranged face-to-face along the b-direction and were piled up in the a-direction, thus forming the stacked bilayer unit with the thickness of d002 = 12.75 A. The elaborate networks of calcium coordinations and hydrogen bondings were formed among the layers and stabilized the crystal structure. Based on the structural parameters of the present beta-CaG crystal, a possible interaction model of phospholipid with calcium ions was proposed. PMID- 1431591 TI - Inhibition of lipoprotein lipase activity by synthetic peptides of apolipoprotein C-III. AB - In this study we have examined effects of synthetic polypeptide fragments of apoC III on the kinetic properties of lipoprotein lipase (LPL) activity. Based on the loss of 79% of LPL-inhibitory activity after CNBr cleavage at the N-terminal portion of apoC-III and a systematic search for synthetic peptides with LPL inhibitory activity spanning the apoC-III sequence, we concluded that the N terminal domain is the most important in the modulation of LPL activity. In addition, there are multiple attachment sites in apoC-III for its interaction with LPL and these sites reside in the hydrophilic sequences of apoC-III. Probably for this reason the intact apo-CIII exhibited higher inhibitory potential than its peptide components. Based on the deduced inhibition constants derived for the synthetic apoC-III1-79 we concluded that apoC-III is likely to exhibit a physiological role in regulating LPL activity since the derived dissociation constants for the LPL-apoC-III interaction are within the physiological concentration range of plasma apoC-III. In addition, as the synthetic apoC-III1-79 lacks the carbohydrate moiety, we also concluded that the presence of the oligosaccharide in native apoC-III is not essential for its inhibitory activity on LPL. The fact that the I50 (concentration for inhibition of LPL at 50% activity) decreases for apoC-III-1 when assayed in the presence of apoC-II indicated that the activator actually caused an increased affinity between LPL and apoC-III and demonstrated that apoC-III does not compete for the activator site of apoC-II. PMID- 1431592 TI - Apolipoproteins, membrane cholesterol domains, and the regulation of cholesterol efflux. AB - Published data related to both cell membrane biology and apolipoprotein structure are reviewed and used to formulate a new model describing the mechanisms of cholesterol efflux from cell plasma membrane to high density lipoprotein (HDL) particles. The central premise of this model is the existence of heterogenous domains of cholesterol within plasma membranes. We propose that cholesterol efflux from cell membranes is influenced by three factors: 1) the distribution of cholesterol between cholesterol-rich and cholesterol-poor membrane domains, 2) the diffusion of cholesterol molecules through the extracellular unstirred water layer, and 3) the transient interaction of segments of the amphipathic helix of the HDL apolipoprotein with cholesterol-poor membrane domains resulting in enhanced cholesterol efflux. PMID- 1431593 TI - Molecular basis of mitochondrial fatty acid oxidation defects. AB - A dozen separate inherited disorders of mitochondrial fatty acid beta-oxidation have been described in humans. This represents about half of the potential sites for genetic error that can affect this important pathway of energy metabolism. As the characterization of these disorders at the clinical and biochemical levels has progressed rapidly, so has the delineation of the molecular defects that underlie them. The most commonly recognized disorder of beta-oxidation is medium chain acyl-CoA dehydrogenase deficiency; a striking feature of this disorder is that there is a single point mutation that accounts for 90% of the variant alleles among patients with medium-chain acyl-CoA dehydrogenase deficiency. Molecular defects of other enzymes in the pathway have been identified, and it seems likely that a complete description of these defects at the molecular level is a realistic goal. In basic biological terms, such studies will lead to a better understanding of the genetic control exerted on this pathway. In clinical terms, they will lead to improved understanding of the molecular pathophysiology of these diseases and may well provide the necessary techniques to proceed with the screening of these disorders. PMID- 1431594 TI - Ionization and self-association of unconjugated bilirubin, determined by rapid solvent partition from chloroform, with further studies of bilirubin solubility. AB - Our studies of equilibrium solubilization of crystals of unconjugated bilirubin (UCB) in buffered aqueous NaCl (1988. J. Lipid Res. 29: 335-348) suggested that the two carboxylic pKa values were 6.8 and 9.3 and the solubility of UCB diacid was 0.1 microM. These data, however, were not ideal, due to possible effects of crystal size, metastability, 96-h incubation times with formation of polar derivatives, impurities in the bilirubin, and imprecision of analyses at low concentrations of UCB ([UCB]). In the present study, designed to determine the pKa values and self-association of UCB, these problems were minimized by solvent partition of UCB from solution in CHCl3 into buffered aqueous NaCl. There was no crystal phase. Equilibrium was attained rapidly (10 min); UCB and CHCl3 were highly purified; and accurate diazo assay of low [UCB] in the aqueous phase, [Bw], was achieved by concentrating the UCB through back-extraction into a small volume of CHCl3. By determining effects on partition rations of varying the [UCB] in the CHCl3 phase, [Bc], we could assess also the self-association of UCB species in the aqueous phase. Partition ratios (P = Bw/Bc) did not differ between initial and repeat extractions, indicating insignificant concentrations of polar UCB derivatives. Similar P ratios were obtained when equilibrium was approached from a supersaturated aqueous phase. At 21-25 degrees C, mu = 0.15, the data (n = 76) fit the equation: log P = log Po + log[1 + 10(pH-A) + 10(2pH-B) + Bc.10(4pH D)]; the bracketed terms reflect P for H2Bo (diacid), HB- (monoanion), B= (dianion), and (B=)2 dimer, respectively. Computer-fitted values for constants (+/- SD) were: Po = P for H2Bo = 5.79 x 10(-5); A = pK1 = 8.12 +/- 0.23; B = pK1 + pK2 = 16.56 +/- 0.10; pK2 = 8.44 +/- 0.33; D = pk22 + 2(pK1 + pK2) -log(2Po) = 37.64 +/- 0.07, and k22 = 0.26 microM-1 [formation constant of (B=)2 dimer]. In ancillary studies, multiple cycles of direct dissolution of UCB crystals revealed a progressive decrease in aqueous solubility of UCB as fine crystals were removed; this effect was minimal in CHCl3. Unlike in water, moreover, varied UCB crystal forms had similar solubilities in CHCl3, with [Bc] = 1.14 mM at saturation. As determined from [Bc]sat.Po, the aqueous solubility of H2Bo was 66 nM.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1431595 TI - HepG2 cell LDL receptor activity and the accumulation of apolipoprotein B and E in response to docosahexaenoic acid and cholesterol. AB - In the present study, the accumulation of apolipoproteins (apo) A-I, B, and E in culture medium was measured after 0, 3, 6, 12, and 24 h of incubation with 150 microM docosahexaenoic acid complexed to 75 microM bovine serum albumin (BSA 22:6), either in the presence or absence of 50 micrograms/ml cholesterol and 4 micrograms/ml 25-hydroxycholesterol (C/25-OH). HepG2 cells incubated with BSA + C/25-OH for 24 h accumulated approximately 2.0-fold greater apoE and B as compared to BSA-treated cells. Moreover, HepG2 cell apoB accumulation after 24 h of BSA-22:6 treatment was approximately 2.0-fold greater than apoB accumulation from cells treated with BSA alone. When BSA-22:6 and C/25-OH were both included in the incubation, apoB accumulation was approximately 5.0-fold greater than BSA treated cells. Comparative studies using BSA-18:1 were carried out for 24 h and showed similar levels of apoA-I, B, and E accumulation in culture medium as compared to BSA-22:6-treated cells. In addition, apoA-I, B, and E mRNA abundance were found to be unaffected by type of fatty acid treatment or length of incubation, averaging 48.2 +/- 7.5, 222 +/- 33.6, and 17.1 +/- 0.7 pg mRNA/micrograms RNA (mean +/- SEM), respectively. As the accumulation of apoB and apoE in culture medium may be modified by HepG2 cell LDL receptor expression, LDL receptor mRNA abundance and LDL receptor activity were quantified at various times over the course of the study. By 6 h of BSA + C/25-OH treatment, LDL receptor mRNA was reduced approximately 2.3-fold, while receptor activity was reduced approximately 1.5-fold, as compared to BSA controls. In an experiment designed to determine uptake of HepG2 cell lipoproteins, 3H-labeled apoB containing lipoproteins derived from HepG2 cells were prepared. The 3H-labeled lipoproteins were 1.25-fold more likely to be removed from the media of HepG2 cells treated with BSA than from cells treated with BSA + C/25-OH. From these results, we postulate that HepG2 cell LDL receptor activity mediates the removal of apoB, E-containing lipoproteins from culture medium and contributes to the lower accumulation of apoB and E observed in culture medium from cells treated with BSA as compared to cells treated with C/25-OH. PMID- 1431596 TI - Discrimination between forms of vitamin E by humans with and without genetic abnormalities of lipoprotein metabolism. AB - To study the mechanisms of discrimination between various forms of vitamin E, four normal subjects, one patient with lipoprotein lipase deficiency, and three patients with abnormal apolipoprotein B-100 production were given an oral dose containing three tocopherols labeled with differing amounts of deuterium (2R,4'R,8'R-alpha-(5,7-(C2H3)2)tocopheryl acetate (d6-RRR-alpha-tocopheryl acetate), 2S,4'R,8'R-alpha-5-(C2H3)tocopheryl acetate (d3-SRR-alpha-tocopheryl acetate), and 2R,4'R,8'R-gamma-(3,4-2H)tocopherol (d2-RRR-gamma-tocopherol). The tocopherol contents of plasma, red cells, and lipoproteins were measured up to 76 h after the dose. In normal subjects all three tocopherols were absorbed and secreted in chylomicrons with equal efficiencies. Both d2-gamma- and d3-SRR-alpha tocopherols peaked at similar concentrations in the other lipoprotein fractions, then decreased similarly, but 2-4 times more rapidly than did d6-RRR-alpha tocopherol. A lipoprotein lipase-deficient patient and a patient with prolonged production of chylomicrons with absent apolipoprotein B-100 also demonstrated the lack of discrimination between tocopherols during absorption. Despite abnormal apolipoprotein B-100 production in two patients, the "VLDL" was preferentially enriched in d6-RRR-alpha-tocopherol. Our results show that there is no discrimination between the three tocopherols during absorption and secretion in chylomicrons, but subsequently there is a preferential enrichment of very low density lipoprotein (VLDL) with RRR-alpha-tocopherol. Catabolism of this VLDL results in the maintenance of plasma RRR-alpha-tocopherol concentrations. PMID- 1431597 TI - Effects of psyllium hydrophilic mucilloid on LDL-cholesterol and bile acid synthesis in hypercholesterolemic men. AB - The goal of the current study was to determine the mechanism of the hypocholesterolemic effect of psyllium using a randomized, double-blind, crossover design. Twenty males (age 44 +/- 4 yr, weight 79 +/- 10 kg) with moderate hypercholesterolemia (total 265 +/- 17 mg/dl, low density lipoprotein (LDL) 184 +/- 15 mg/dl) were studied at baseline (B) and after randomization to receive a 40-day course of 15 g/day of either psyllium (Ps) or placebo (Pl) (cellulose). After a washout period (11 +/- 2 days), subjects were crossed over to the other fiber treatment for an additional 40 days and restudied. Intestinal cholesterol absorption, cholesterol synthesis in isolated peripheral blood mononuclear cells, bile acid kinetics, gallbladder motility, and intestinal transit were measured at each study period. Psyllium lowered LDL cholesterol (x:184 (B), 169 (Ps), and 179 (Pl) mg/dl; Ps vs. B,Pl: P less than 0.004, P less than 0.02), decreased relative cholesterol absorption (x:51 (B), 45 (Ps), and 49 (Pl) %; Ps vs. B,Pl: P less than 0.03, P less than 0.03), did not alter absolute cholesterol absorption, and increased the fractional turnover of both chenodeoxycholic acid (x:0.176 (B), 0.203 (Ps), and 0.170 (Pl) day-1; Ps vs. B,Pl: P less than 0.0001, P less than 0.01) and cholic acid (x:0.303 (B), 0.411 (Ps), and 0.301 (Pl) d-1; Ps vs. B, Pl: P less than 0.006, P less than 0.002). Bile acid synthesis increased in subjects whose LDL cholesterol was lowered by more than 10% (Ps vs. B: 1304 +/- 489 vs 992 +/- 307 mumol/day, P less than 0.006; Ps vs. PI: 1304 +/- 489 vs. 914 +/- 321 mumol/day, P less than 0.0002). We conclude that psyllium lowers LDL cholesterol primarily via stimulation of bile acid synthesis. PMID- 1431598 TI - Differing effects of cholesterol and taurocholate on steady state hepatic HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities and mRNA levels in the rat. AB - We investigated the effects of cholesterol, cholestyramine, and taurocholate feeding on steady state specific activities and mRNA levels of hepatic 3-hydroxy 3-methylglutaryl (HMG)-CoA reductase and cholesterol 7 alpha-hydroxylase in the rat. Interruption of the enterohepatic circulation of bile acids (cholestyramine feeding) increased total HMG-CoA reductase activity 5-fold. Cholesterol and taurocholate administration suppressed total microsomal HMG-CoA reductase activities 87% and 65%, respectively. HMG-CoA reductase mRNA levels increased 3 fold with cholestyramine, did not decrease significantly with cholesterol feeding, but were markedly decreased after taurocholate treatment. Cholesterol 7 alpha-hydroxylase activity increased 4-fold with cholestyramine and 29% during cholesterol feeding, but decreased 64% with taurocholate. Cholesterol 7 alpha hydroxylase mRNA levels rose 150% and 50% with cholestyramine and cholesterol feeding, respectively, but decreased 73% with taurocholate. The administration of cholesterol together with taurocholate prevented the decline in cholesterol 7 alpha-hydroxylase mRNA levels, but inhibition of enzyme activity persisted ( 76%). Hepatic microsomal cholesterol concentrations increased 2-fold with cholesterol feeding but did not change with taurocholate or cholestyramine treatment. These results demonstrate that mRNA levels of HMG-CoA reductase are controlled by the hepatic taurocholate flux, whereas mRNA levels of cholesterol 7 alpha-hydroxylase are controlled by the cholesterol substrate supply. These end products, cholesterol and bile acids, exert post-transcriptional regulation on HMG-CoA reductase and cholesterol 7 alpha-hydroxylase, respectively. PMID- 1431600 TI - Preparation of lyso-GM1 (II3Neu5AcGgOse4-long chain bases) by a one-pot reaction. AB - A simple procedure is described for preparing lyso-GM1, a GM1 derivative that lacks the fatty acid moiety, starting from GM1 ganglioside using a one-pot reaction. Ganglioside deacylation was carried out in KOH/propan-1-ol in the absence of oxygen. The yield of lyso-GM1 under optimal conditions (6 h, 90 degrees C, 0.2 N KOH, 1 mM GM1) was 54%. The chemical structure of lyso-GM1 was determined by 1H-NMR and FAB-MS analyses, thus proving that the acetamide groups of galactosamine and sialic acid units were not affected during the deacylation reaction. PMID- 1431599 TI - beta-Glucocerebrosidase activity in murine epidermis: characterization and localization in relation to differentiation. AB - The intercellular lipids of the stratum corneum, which are highly enriched in ceramides, are critical for the mammalian epidermal permeability barrier. During the terminal stages of epidermal differentiation, the glucosylceramide content is dramatically reduced, while the content of free ceramides increases. To investigate whether beta-glucocerebrosidase (beta-GlcCer'ase) could be responsible for this change in lipid content, we characterized its activity in murine epidermis, compared enzyme activity to other murine tissues, and localized beta-GlcCer'ase activity within the epidermis. Epidermal extracts demonstrated linear 4-methylumbelliferyl-beta-D-glucose hydrolysis (to 3 h) with protein concentrations between 1 and 250 micrograms/ml. Whole epidermis contained comparable beta-glucosidase activity (9.1 +/- 0.4 nmol/min per mg DNA) to murine brain and liver, and 5-fold higher activity than spleen. Epidermal beta glucosidase activity was stimulated greater than 15-fold by sodium taurocholate at pH 5.6, and inhibited at acidic pH (3.5-4.0). Bromoconduritol B epoxide (greater than or equal to 1.0 microM), inhibited epidermal enzyme activity by greater than 75%, while activity in brain, liver, and spleen was only inhibited by 6, 17, and 14%, respectively. Moreover, beta-GlcCer'ase mRNA expression in murine epidermis exceeded levels in liver, brain, and spleen. Finally, beta GlcCer'ase activity was highest in the outer, more differentiated epidermal cell layers including the stratum corneum. In summary, mammalian epidermis contains an usually high percentage (approximately 75%) of beta-glucocerebrosidase activity, and the concentration of activity in the more differentiated cell layers may account for the replacement of glucosylceramide by ceramides in the outer epidermis. PMID- 1431601 TI - Galactosylceramide containing omega-amino-fatty acids: preparation, characterization, and sulfotransferase acceptor. AB - For preparation of an affinity ligand, an N-fatty acyl moiety of galactosylceramide (GalCer) was chemically replaced with omega-amino-fatty acid including amino-n-hexanoic acid or amino-n-dodecanoic acid to obtain omega aminoGalCer. For the synthesis of the compound, galactosylsphingosine (GalSph) was coupled with N-trifluoroacetyl omega-amino-fatty acid which was prepared by a reaction with S-ethyltrifluorothioacetate. After removal of the N-trifluoroacetyl group in a mild alkaline solution, in which an N-fatty acyl group was retained, aminoGalCer composed of an N-hexanoyl or an N-dodecanoyl group was obtained with an overall yield of 90%. Their chemical structures were confirmed by proton nuclear magnetic resonance and fast atom bombardment-mass spectrometries. These aminoGalCers and GalSph as well as immobilized aminoGalCer were sulfated by a glycolipid sulfotransferase from rat kidney. Furthermore, immobilized aminoGalCer on gel matrix was used for affinity chromatography of the sulfotransferase, resulting in an excellent increase in the purification (14,000-fold) with a recovery rate of 40%. PMID- 1431602 TI - Improved procedures for the determination of lipid phosphorus by malachite green. AB - We have developed two procedures for the measurement of lipid phosphorus based on interaction between phosphomolybdenum and malachite green. One method, the "micro" assay uses 50-200 microliters of HClO4 and has a sensitivity range of 0.01-1.5 micrograms phosphorus. The second method, the "macro" assay, has a sensitivity range of 0.03-5.0 micrograms phosphorus with 100-500 microliters HClO4. Both assays are very reproducible with day to day standard deviations of less than 6% between triplicates irrespective of the HClO4 content used. At different concentrations of HClO4, each method was successfully used to determine the phosphorus content in phosphatidylethanolamine and sphingomyelin standards that covered the proposed sensitivity ranges. The increased range, sensitivity and greater volumes of HClO4 permitted in the procedures represent significant improvements over existing methods. PMID- 1431603 TI - [Circulating lupus coagulants. A paradox in vascular pathology]. AB - Lupus anticoagulants (LA) are acquired inhibitors of coagulation related to the antiphospholipid antibodies. Paradoxically, these anticoagulants do not expose patients to the risk of hemorrhage but, on the contrary, to a thrombotic risk. The association in a patient of an antiphospholipid antibody and a clinical manifestation (thrombosis or equivalent) defines the antiphospholipid syndrome. This syndrome is termed primary or secondary according to whether it appears as an isolated disorder or is associated with an identified disease, frequently autoimmune (systemic lupus erythematous or lupus related syndrome). Clinical complications of LA are arterial or venous thrombosis at various sites. They are frequently recurrent, and deep venous thrombosis of leg, oculo-cerebral ischemic lesions and heart valve complications have all been well documented. Thrombosis of the microcirculation can cause tissue or organ disfunction, the most characteristic effect being repeated abortions. Laboratory demonstration of LA is difficult when the inhibitor is weak, and this should be completed by tests for other antiphospholipid antibodies. Clinical studies are necessary to assess the thrombotic risk of the LA in different clinical conditions and to evaluate the need and type of antithrombotic treatment. The LA are heterogeneous and only a small proportion of patients with LA will develop thrombosis. New tests capable of predicting the thrombotic risk, bases on the physiopathological mechanisms with which LA interfere in vivo, are currently being investigated. PMID- 1431604 TI - [Surgery of aneurysms of the abdominal aorta in 1992. Lessons of a decade]. AB - Perioperative mortality of abdominal aortic aneurysm (AAA) remains at a mean of 3% in asymptomatic cases, 6% when symptomatic and 50% when ruptured while many patients with ruptured AAA die prior to surgery. This has changed little over the last decade. The causes of this stagnation are analyzed, strategic choices as a function of clinical situations, size of aneurysm, and associated lesions exposed, and means explored to improve the prognosis. Since the perioperative mortality rate appears incompressible, an improvement in the prognosis of AAA can be obtained only by a combined medical effort. This requires the more rapid recognition of prodromal symptoms of rupture, the detection of a larger number of asymptomatic AAA and improved postoperative life expectancy, already reasonable, by more rigorous vascular and cardiologic surveillance. PMID- 1431605 TI - [Duplex ultrasonography in the diagnosis of deep vein thrombosis of the legs. Agreement between two operators]. AB - The operator-dependent nature of venous Duplex-ultrasonography diagnosis of deep venous thrombosis (DVT) of the leg is the principal reproach applied to it and a reason for delaying use. The aim of the present study was to evaluate concordance between two operators, with rigorous application of the same methodology of exploration of the venous axes. The study included 82 patients under hospital care, randomly selected from among those referred for the first Duplex ultrasonography examination for DVT, and having accepted to undergo 2 consecutive explorations, one by each of the two operators. The two operators evaluated independently, for the 19 venous axes of the legs: 1: the interpretability of the examination, 2: the differential diagnosis between: absence of thrombus, presence of thrombus, nonconclusive examination, and 3: the score for the DVT extension. Evaluation of concordance of diagnosis was by Cohen's kappa coefficient, calculated on the positive diagnosis of DVT and the site of the most proximal thrombus. Extension scores were compared by calculation of the coefficient of correlation "r". Interpretability rates were 92% and 91% respectively for the two operators, 35 DVT being diagnosed in 27 patients by operator A and 36 DVT in 27 patients by operator B. The kappa coefficient for diagnosis of DVT with localization in the affected leg was 0.90 [0.81-0.98]. It was 0.89 [0.73-1] for proximal lesions, 0.86 [0.74-0.97] for the lower leg level, and 0.79 for localization of the proximal extremity of the thrombus. Extension scores evaluated by the two operators were 2.88 and 3.14 respectively, with a coefficient of correlation between the extension scores of 0.96. The 5 diagnostic divergences concerned the lower leg level; the 2 localization discordances concerned: the frontier zones leg-lower popliteal, lower femoral-upper popliteal. Good concordance between results of the two operators using Duplex ultrasonography exploration was obtained even though the majority of the DVT were in the calf, a region known to be explored with difficulty. Overcoming the operator-dependent character of Duplex-ultrasonography by a rigorous exploratory methodology could make it the future reference examination for the diagnosis of DVT. PMID- 1431606 TI - [Use of an active clinical maneuver for diagnosis of popliteal artery entrapment]. AB - Overall incidence rate of popliteal artery entrapment syndrome is certainly underestimated. The aim of this work was to test and to evaluate the interest of a clinical maneuver of active and repetitive ankle extensions in upright position, for the screening, the diagnosis and the follow-up of patients with popliteal artery entrapment. During a 3 year period, this maneuver was used in 10 patients (16 popliteal artery entrapments) and in 50 age-matched controls. The results of the maneuver were compared to the results of functional vascular investigations. For all the patients the maneuver had to be stopped before 20 movements whereas it could be continued up to 50 movements for all the controls. The maneuver was easy to perform, reliable and constant in its results. The earlier the maneuver was stopped the more critical was the trouble at functional vascular investigations. We believe that this maneuver is of great help for early diagnosis of popliteal artery entrapment, assessment of its severity and follow up treated patients. It could also help to detect athletes with asymptomatic popliteal entrapment. PMID- 1431607 TI - [Electric stimulation of the spinal cord in arterial diseases of the legs. A multicenter study of 244 patients]. AB - From January 1985 through January 1990, 244 patients (168 males, 76 females, mean age: 69 +/- 14 years) received epidural spinal cord stimulation for the treatment of advanced, nonreconstructable, peripheral vascular disease of the lower limbs due to atherosclerosis in 180 patients, atherosclerosis and/or diabetes in 49, and thromboangiitis obliterans in 15 patients: previous surgery included 101 bypass-grafts in 70 patients, 51% of which below the knee, and 117 sympathectomies in 113 patients as the last resource in face of distal peripheral vascular disease of the lower limbs. Mean ankle-to brachial systolic pressure ratio was .31 +/- .34 on symptomatic limbs; due to pain and advanced disease, walking capacity was assessed in only 151 patients, either on treadmill in 25, or in a metered corridor in 126; angiogram of the lower limbs was performed in every patient unless one not older than three months was readily available; pain at rest was assessed after an analogical scale; partial transcutaneous oxygen tension was measured on the dorsum of the fore-foot of 77 symptomatic limbs (mean: 13.35 +/- 14 mmHg). According to clinical and functional evaluation, 18 patients had exertional ischemia (group I), 87 had permanent ischemia with pain at rest and no tissue loss (group II), and 139 had chronic tissue loss (group III), including 93 ischemic ulcers (mean surface: 3.7 cm2, mean duration: 3.5 months) in 88 patients, 27 limited gangrene, and 24 previous limited non-healing distal amputation. After temporary spinal cord stimulation at T12-L1 level (mean duration: 9 +/- 4 days) with a percutaneous quadripolar electrode lead had allowed for selection of responders, 212 patients received an implantable neurostimulator.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431608 TI - Oscillometry of radial artery in acrocyanosis and cold sensitivity. AB - Acrocyanosis is reassessed on the basis of 34 new patients with diagnostic clinical features. The most useful tests are the skin temperature differences (STD) between wrist and end of fingers (or ankle and end of toes) and oscillometry over the radial and dorsalis pedis and posterior tibial arteries. Capillaroscopy of the conjunctival and nailfold vessels is useful in half the patients. Capillary resistance was not helpful. STD of 1.5 degrees C or more between skin of wrist or ankle and fingertip or toetip, is usually associated with more severe disease and capillary abnormalities on microscopy, and with reduced oscillometry (to 1 or less) over the radial arteries and dorsalis pedis and posterior tibial arteries. Reduced oscillometry is more associated with abnormalities than the other tests, and more than STD. The work of Mulvany and his colleagues suggests an explanation for the low oscillometry. Larger vessels than the arterioles and digital vessels can become resistance vessels in various circumstances. It is likely that the radial artery and vessels of similar diameter can temporarily act as resistance vessels in patients with acrocyanosis in a low temperature environment. PMID- 1431609 TI - [Ambulatory and hemodynamic treatment of venous insufficiency (CHIVA cure). Study of 96 patients operated on between June 1988 and June 1990]. AB - 96 patients were treated in two years by Ambulatory and Hemodynamic Treatment of Varicose Veins (CHIVA cure), representing 131 legs that underwent surgery. 71 patients (74%) representing 102 CHIVA cures in the long saphena territory were followed up, with a maximum of 28 months of follow-up. The CHIVA cure represents a new and interesting therapy: ambulatory, painless, it allows a very early resuming of normal life. The follow-up shows that the aesthetic and functional results are especially satisfying and seem to be steady. The CHIVA cure certainly neglects the histological and parietal aspects of venous incompetence but the treatment of the hemodynamic factor is effective. It can be applied on every type of varicose veins concerning the long saphena territory, provided that the deep venous system is normal. The interest of CHIVA cure concerning the short saphena territory remains to be demonstrated. Arteritic patients, patients with coronary arteries diseases, sportmen, young patients with a brief evolutive potential, especially women, are the best indications. The CHIVA cure is a reliable strategy in the short and medium term, offering excellent aesthetic and functional results that still have to be confirmed in the long term and or a large scale. PMID- 1431610 TI - [Results of ambulatory and hemodynamic treatment of venous insufficiency (CHIVA cure)]. AB - From January 1987 to December 1988, 100 conservative and hemodynamic treatments of superficial venous insufficiency in great saphenous vein territory, have been done on 86 patients. They were 32 men, whose mean age was 53.7 years, and 54 women, whose mean age was 44.5 years. Indication for surgery was mainly functional in 28 cases, esthetic in 26 cases, both in 25 cases and trophic problems in 21 cases. Ligation of the sapheno-femoral junction has been done in 91 cases (62 clips, 9 clips and ligations, 11 ligations, 9 sutures). Distal interruption has been done above knee in 24 cases, below knee in 50 cases, and both in 16 cases. Early postoperative complications have been one septic collection of the groin, one hematoma of the groin, one durable contusion of the saphenous nerve, and 21 superficial venous thrombosis. There were six thrombosis of excluded branches, seven subtotal thrombosis of the saphenous and height partial thrombosis of the saphenous vein. Subtotal thrombosis of the saphenous vein were due either to a mistake in position of distal ligation in three cases, either to a too large saphenous vein in four cases. Five out of height partial thrombosis occurred on saphenous veins larger than ten millimeters. Follow up was obtained, in 1990, so that all patients had at least one year of follow-up. Seven patients have been lost for follow-up. Three patients had recurrence because of failure of the clip. An additional procedure was necessary in 30 patients. Functional results were correct in 89% of patients, and esthetical results in 68% of patients. PMID- 1431611 TI - [Chilblains]. AB - Chilblains represents an idiopathic vascular cutaneous benign acral syndrome. Epidemiology and basic mechanisms remain hypothetic and the treatment is controversial. The patients exhibit pruritic, redness painful, burning acral patches or plaques on the toes and/or fingers. The disease is bilateral, youthful and influenced by exposure to cold. Spontaneous healing is common when spring arrives and relapse is frequent on the following winters. There is no systemic symptom and laboratory studies are normal. The physical examination is sufficient for diagnosis. Histologic examination shows vascular and perivascular capillary and venular lymphocyte infiltrates without necrosis nor leukocytoclasia. The differential diagnosis includes: lupus, cold urticaria, acrocyanosis, erythermalgia, vasculitis and the Blue Toe Syndrome. Treatment includes prophylactic measures against cold and calcium channel inhibiting drug. In more severe cases thyrocalcitonin and hemodilution might be helpful. PMID- 1431612 TI - [Interruption of the infra-renal inferior vena cava with azygos continuation. Case report]. AB - The authors report a case of congenital interruption of the inferior vena cava with azygos continuation with a deep venous thrombosis of the left lower extremity. It is a rare congenital abnormality which is most of the time asymptomatic. However such an abnormality may be a problem in case of cardiac catheterization or thoracic surgery. PMID- 1431613 TI - [Acute thrombosis of the right renal vein. Two cases with coagulopathies]. AB - We report two cases of renal vein thrombosis, unusual because of acute expression, right renal vein localization, absence of the usual renal or perirenal causes, surgical management and a never before reported etiology. In one case the thrombosis was secondary to primary antiphospholipid syndrome, in the other it was secondary to heparin associated thrombocythemia. In this case surgical management was performed during prostacyclin infusion. PMID- 1431614 TI - [Ambulatory and hemodynamic treatment of venous insufficiency (CHIVA cure). Report of an atypical case]. AB - After a brief introduction describing the principle, strategy and tactics of hemodynamic treatment of venous insufficiency in ambulant patients, the following atypical case is described. Ms P., aged 38 years, presented a functional symptomatology including waking at night and was obliged to get out of bed. Varices were moderately visible but she asked for treatment for esthetic reasons. A future pregnancy was discounted. Clinical examination and the pulsed ultrasound Doppler cartogram showed incontinence of the internal perineal, opening from the genitofemoral fold and rejoining the summit of Jacomini's vein arch. The dorsal segment of Jacomini's vein was incontinent with a retrograde flux and rejoined an incontinent short saphenous continuing as a type III shunt. The cartogram obtained, the strategy decided and the intervention carried out on 19 June 1990 are illustrated by photographs. At 4 month follow up and despite the heat wave of summer 1990, all functional signs had disappeared and a sufficiently esthetic result had been obtained. Unexpectedly, the patient announced that she was pregnant. PMID- 1431615 TI - Symmetry-breaking bifurcation: a possible mechanism for 2:1 frequency-locking in animal locomotion. AB - The generation and control of animal locomotion is believed to involve central pattern generators - networks of neurons which are capable of producing oscillatory behavior. In the present work, the quadrupedal locomotor central pattern generator is modelled as four distinct but symmetrically coupled non linear oscillators. We show that the typical patterns for two such networks of oscillators include 2:1 frequency-locked oscillations. These patterns, which arise through symmetry-breaking Hopf bifurcation, correspond in part to observed patterns of 2:1 frequency-locking of limb movements during electrically elicited locomotion of decerebrate and spinal quadrupeds. We briefly describe how our theoretical predictions could be tested experimentally. PMID- 1431616 TI - The "new" review of the literature. PMID- 1431617 TI - Evaluation of neck muscle strength with a modified sphygmomanometer dynamometer: reliability and validity. AB - OBJECTIVE: Determine test-retest reliability, normative data and clinical validity of isometric muscle strength testing in the neck with a modified sphygmomanometer dynamometer (MSD). DESIGN: Analytic survey. Paired trials of various muscle strength tests were conducted on convenience samples of normal subjects and consecutive samples of symptomatic subjects. SETTING: Outpatient chiropractic research clinic. PATIENTS/SUBJECTS: For study 2, 40 normal male subjects, average age 25 +/- 2 yr, were studied for reliability and normative data. For study 3, 24 symptomatic patients, 12 males and 12 females, average age 39 +/- 7 yr, were studied, 8 with "whiplash"-type injuries (average duration 22.5 wk) and 16 with nontraumatic chronic neck pain (average duration 110 wk). INTERVENTION: No therapeutic intervention is reported. MAIN OUTCOME MEASURE: Pressure levels generated by subjects against a modified sphygmomanometer-type dynamometer as measured in kilopascals. RESULTS: Study 1. Repeated paired trials of a standardized weight column (20 lbs) produced a coefficient of variation of 0.84% and virtually no difference between the means of the first vs. second trials. Study 2. High test-retest correlation coefficients were found for all ranges of motion (.79-.97). Right-to-left asymmetry in rotation and lateral flexion was within 6-8%. The flexion/extension ratio was .57:1, indicating that in normal subjects, flexion was approximately 40% lower than extension. Lower cutoffs were established as the mean--1 SD as follows (in kPa): flexion--3300, extension--5800, rotation--5200 and lateral flexion--6200. Coefficients of variation ranged from 25 to 29%. Study 3. Differences between paired trials were analyzed by intraclass coefficients, which were very high (.95-.99), and by percentages, which ranged from 4 to 10.4%, with an average of 7%, indicating a high degree of test-retest consistency. The mean values for all symptomatic subjects for flexion, extension, right rotation and right lateral bending were all well below the normal cutoff values as found in study 2. The flexion/extension ratio for whiplash subjects was 0.25:1.00, which is half of that of normal subjects. CONCLUSIONS: The MSD has been found to be a reliable instrument for the evaluation of isometric muscle strength in the neck in normal and symptomatic subjects. Normative values for absolute test levels, bilateral symmetry and flexion/extension ratios have been determined. A symptomatic group demonstrated significant deviations from these norms in the form of reduced strength levels and reduced flexion/extension ratios, while still maintaining very high levels of test-retest consistency and bilateral symmetry. The MSD appears very promising in the evaluation of neck-injured patients. PMID- 1431618 TI - A roentgenological evaluation of the relationship between segmental motion and malalignment in lateral bending. AB - OBJECTIVE: A radiographic study was undertaken to determine the relationship between static vertebral malalignment and segmental lumbar motion in lateral bending. DESIGN: Survey. SETTING: Chiropractic college student health center and private chiropractic clinic. PARTICIPANTS: 249 subjects: 114 with low back pain, 29 asymptomatic with no history and 106 asymptomatic with history. Of these, 194 were freshman volunteers and 55 were new private clinic low back pain patients. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Net lumbar segmental tilt and rotation in lateral bending: corrected and uncorrected for segmental malposition with the patient standing in the upright neutral position. RESULTS: There was moderate to good negative correlation of malalignment with segmental tilt motion and segmental motion asymmetry (r = -.42 to -.89, p less than .001). Correlation of malalignment with motion from the ideal neutral segmental position of perfect alignment was modest (r = .16-.42). A large variation in segmental motion was found for all segmental malalignments. CONCLUSIONS: This study suggests that malalignment is associated with segmental tilt motion in lateral bending, although large subject variability greatly compromises predictability on an individual basis. This study also indicates that segmental malposition may complicate the palpation of active range of motion. This is because the malalignment itself may facilitate a greater arc of segmental motion in the direction of comparative restriction in movement from the ideal neutral position to the extreme of lateral flexion. PMID- 1431619 TI - Stability of paraspinal tissue compliance in normal subjects. AB - OBJECTIVE: The following studies were performed in order to evaluate the stability of paraspinal tissue compliance measurements. Tissue compliance is a measure of the consistency or firmness of soft tissue and is determined by a hand held tissue compliance meter. DESIGN: Descriptive and blinded time course intervention measurements. SETTING: All measurements were performed on subjects placed in the prone position on flat tables in a laboratory setting. PARTICIPANTS: Forty asymptomatic volunteer subjects. INTERVENTION: Tissue compliance measurements of the T6 and L3 paraspinal regions. MAIN OUTCOME MEASURE: Tissue compliance measurements recorded as millimeters of penetration of a metered probe. RESULTS: Data from this study indicate that paraspinal tissue compliance at the T6 and L3 regions does not change significantly over a 10-min interval, is not effected by the testing intervention and the number of abnormal left/right tissue compliance asymmetries is appropriate (5%) for a normal population of subjects. CONCLUSIONS: These findings tend to support the utility of tissue compliance as a possible tool for the evaluation of paraspinal soft tissue. PMID- 1431621 TI - Proximal tibiofibular joint dysfunction and chronic knee and low back pain. AB - This article reports a case of joint dysfunction of the proximal tibiofibular joint that produced knee, thigh and low back pain of 5 yr duration. An injury of a simple nature apparently caused the onset of symptoms. Manipulation of the proximal tibiofibular joint resulted in immediate and dramatic relief of symptoms. This case illustrates how a relatively minor incident can result in longstanding pain and disability. Examination and treatment procedures for the proximal tibiofibular joint dysfunction are described. PMID- 1431620 TI - Skin temperature assessment for neuromusculoskeletal abnormalities of the spinal column. AB - OBJECTIVE: A qualitative review of the scientific literature on thermographic instrumentation for detecting neuromusculoskeletal abnormalities of the spinal column was made. Electronic infrared instrumentation (telethermography), liquid crystal thermography and various hand-held devices were scrutinized in terms of reliability and comparison with other diagnostic tests (e.g., computed tomography, myelography, electromyography, magnetic resonance imaging). DATA SOURCES: A Medline literature search was performed from 1966 through 1990. English language material was retrieved using the following key words: thermography and spine, spinal injuries, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, sacroiliac joint, lumbosacral region, back or neck. The Index to Chiropractic Literature was also reviewed. The categories of skin temperature and thermography were scrutinized. Chapters of texts and nonpublished works were not incorporated. STUDY SELECTION: Studies involving the comparison of thermographic findings with those of other tests were the primary focus of the review. Case reports, as well as the use of thermography as an outcome measure, were also studied. Interexaminer reliability studies are reported. DATA EXTRACTION: The study populations are characterized as well as binding procedures, if any. The authors' statistical work, if applicable, is presented and criticized. DATA SYNTHESIS: Relatively few reliability studies exist for thermography. Emphasis has been on validity studies that compare the results of the thermogram with other reference tests. There has been a general lack of high quality research design (e.g., blinding) throughout the thermographic literature base. The sensitivity of the various thermographic instrumentation has shown encouraging results, although this must be tempered with the generally poor design of many studies. Specificity, in contrast, has shown mixed results. The review indicated telethermography to be a sensitive diagnostic procedure for detecting abnormalities, such as disc protrusion, of the lumbar and cervical spine. Liquid crystal thermography effectiveness is difficult to determine due to the paucity of blinded investigations, although normative data for the cervical spine and upper extremities is present. Literature on the various hand-held instruments has revealed moderate levels of examiner reliability for infrared devices, with less information available for thermocouple instruments. Normative data for hand-held instruments is absent. CONCLUSION: Continued investigation is needed in the area of thermographic research in light of the paucity of blinded and/or controlled investigations. More sensitive neurophysiological and anatomical measures must be used when comparing the results from thermography. The lack of an available gold standard for comparing thermographic findings has been problematic. Future research should focus on thermography as a noninvasive outcome measure and interpreter reliability. PMID- 1431623 TI - The defense of Thomas Kuhn (and chiropractic). PMID- 1431622 TI - Magnetic resonance imaging versus computed tomography scan: accurate diagnosis of soft tissue lesions. AB - Due to their cost effectiveness and accessibility, computed tomography (CT) scans are being utilized when magnetic resonance imaging (MRI) appears to be the diagnostic technique of choice. Because of their availability, CT scans are still used for diagnosis of disc herniations. MRI may, however, be superior in its specificity. In taking into account the subjective complaint and orthopedic and neurological findings, a disk herniation can often be diagnosed without a CT scan or MRI. However, should the patient fail to respond to conservative care or show unusual symptoms, an MRI is indicated. This article discusses a case where MRI would be the imaging procedure of choice. PMID- 1431624 TI - The physics of spinal manipulation. PMID- 1431625 TI - A blinded randomized clinical trial of manual therapy and physiotherapy for chronic back and neck complaints physical outcome measures. PMID- 1431626 TI - Shades of straight: diversity among purists. PMID- 1431627 TI - Chiropractic adjustment in the management of visceral conditions: a critical appraisal. PMID- 1431629 TI - Journal citation tracking and journal indexing. PMID- 1431628 TI - Lumbar motion trends and correlation with low back pain. Part I. A. roentgenological evaluation of coupled lumbar motion in lateral bending. PMID- 1431630 TI - Proposal for establishing structure and process in the development of implicit chiropractic standards of care and practice guidelines. AB - With the advent of health care's "era of accountability", the chiropractic profession is now faced with generating implicit standards and guidelines for care or having it done for us by outside agencies. Already we see chiropractic groups in individual states and provinces being pressured into naive efforts of guideline development. Current knowledge and experience are available through recent health care literature that clearly defines the structure and process of guideline development and offers suggestions on how to measure outcomes of those processes. In addition, the United States Congress has directed a new federal agency to oversee this activity and monitor outcomes of quality improvement programs. The time has come for the chiropractic profession to define its exact role in health care delivery and develop implicit standards of care and practice guidelines. This sentinel effort should be managed by a commissioned body of empaneled experts that generally represent the academic and clinical chiropractic profession. A protocol for selection of these panelists and the panel chairperson needs to be developed and memorialized. Appropriate methodology (with definitions) needs to be developed for the process of standards/guideline development. Adherence to the accepted structure and process of guideline development will ensure the continuity of this dynamic process in the coming generations. This proposal offers a preliminary definition of the structure and process, including a "seed" policy statement and decision flow chart, specific to guideline development. Once the structure and process of guideline development for chiropractic are defined, the profession can then present this product to federal and state agencies, private sector health care purchasers, patient advocacy groups and other stakeholders of chiropractic care.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431631 TI - Differentiation of active and latent trigger points by thermography. AB - OBJECTIVE: This study tested whether two distinct thermographic patterns attributed to myofascial trigger points could distinguish between active and latent trigger points. DESIGN: A retrospective chart survey was undertaken with thermographic data divided into two groups: a) increased thermal emission only over the trigger point and b) over the area of pain referral. The criterion standard used in a blinded comparison was physical examination findings separating active from latent trigger points. SETTING: All cases were drawn from a private practice referral center for thermographic evaluation of neck and low back injuries. PATIENTS: A sample of 65 cases showing physical examination findings of trigger points was chosen from 229 consecutive motor vehicle accident case files. RESULTS: There was moderate agreement between the two methods of differentiating active from latent latent trigger points (Kappa = 0.44) with a specificity of 0.70 and a sensitivity of 0.74. When cases in which spinal segmental dysfunction were eliminated, the agreement increased (Kappa = 0.54) with specificity of 0.82 and sensitivity of 0.74. CONCLUSIONS: Thermography may be a useful tool in distinguishing active from latent trigger points, but the thermal imaging of spinal joint dysfunction may be a compounding factor. PMID- 1431632 TI - Line drawing analyses of static cervical X ray used in chiropractic. AB - OBJECTIVE: This review article identifies the chiropractic techniques used to assess the structure of the cervical spine as seen on the static cervical radiograph. DATA SOURCES: On-line search of MEDLINE, key words, radiograph and X ray in combination with cervical spine (vertebrae); the Chiropractic Research Archives Collection (CRAC); indexes published in the Journal of Chiropractic Research; conference proceedings from Annual Biomechanics Conference of the Spine, FCER sponsored conferences and Annual Upper Cervical Spine Conference; references identified from bibliographies of pertinent articles; a telephone poll of radiography/technique instructors at chiropractic colleges. STUDY SELECTION: Techniques that quantitatively assess relative alignment of skeletal structures or distortion of the spinal column. DATA EXTRACTION: Techniques were grouped according to the structures analyzed and the views used. DATA SYNTHESIS: Variables and artifacts that limit the reliability or validity of static cervical X ray line drawing analysis were identified and the techniques assessed for their reported reliability and validity. CONCLUSIONS: Reliability studies exist showing that inter- and intraexaminer reliability are sufficient to measure lateral and rotational displacements of C1 to within +/- 1 degree. This amount of error allows objective analysis of upper cervical X rays to detect changes in the angular positional relationships of radiographic images on the order of those already seen clinically. Methods of cervical analysis that use relative angular measures of skeletal positioning are best able to control the effects of radiographic distortion. The accuracy of the analysis methods has not been ascertained to establish the extent to which angular measurement of vertebral relationships actually reflect three-dimensional movement. It is not known how much of the changes that are seen in pre/post-radiograph sets are due to positioning changes of the patient between radiographic procedure, and how much are due to actual changes of skeletal relationships brought about by adjustment. PMID- 1431633 TI - Compression fractures in patients undergoing spinal manipulative therapy. AB - Increasing numbers of elderly patients are currently seeking chiropractic care. One condition commonly seen in the elderly is osteoporosis of the spine, which carries with it the risk of compression fractures. We present four cases in which patients were noted to have compression fractures following chiropractic adjustments. In each of these cases, serious questions are raised concerning the relationship between the adjustment and the occurrence of fracture. What is clear is that failure to diagnose a compression fracture, together with the application of adjustment into the area of fracture, can increase symptoms and prolong disability. It is recommended that patients with osteoporosis who have suffered a fall or injury be X rayed before treatment is given. In addition, special care should be exercised in elderly patients with osteoporosis. PMID- 1431634 TI - Quackery vs. accountability in the marketing of chiropractic. PMID- 1431635 TI - Chiropractic clinical teaching. PMID- 1431636 TI - Rotator cuff disease: current trends in orthopedic management. PMID- 1431637 TI - A meta-analysis of clinical trials of spinal manipulation. PMID- 1431638 TI - Digesting government's regulatory alphabet soup. AB - The impact of the governmental regulatory acronyms implemented during this year will prove to be very similar to how implementation of the Prospective Payment System (PPS) via DRGs affected hospitals a decade ago. Those hospitals that realized the dimensional shift in their industry and made prudent business decisions and adjustments have not only survived their era of payment reform but have also flourished. Those hospitals which did not recognize the regulatory changes, or chose to ignore the changes, have not succeeded, many paying the ultimate price of business failure. The impact on physicians will be quite similar. Physicians that adopt proven, sound, business principles and accept the absolute need to be informed and pro-active, will not only succeed, but they too, will flourish. Physicians who choose otherwise, quite frankly, risk practice failure. A few years ago, the American Hospital Association published what I believe is the ultimate statement of health care regulatory bureaucracy. The publication boasted 80 pages, containing more than 2,000 entries. Its title was Acronyms and Initialisms in Health Care Administration. With the addition of the regulatory acronyms implemented during 1992, the size of that publication has probably more than doubled by now. Being able to digest this regulatory alphabet soup has its benefits; not only will physicians feel more comfortable in their knowledge of being in regulatory compliance, it may also help physicians focus on the best methods of managing their practices and ultimately, their careers. PMID- 1431639 TI - Are patients predisposed to sue their physicians? PMID- 1431640 TI - U.S. Supreme Court reaffirms right to abortion while permitting some state regulation. PMID- 1431641 TI - Hospital Medical Staff Section--your access to action. PMID- 1431642 TI - Alcoholics anonymous and addicted health professionals: the Georgia experience. PMID- 1431643 TI - The changing face of primary hyperparathyroidism. AB - The introduction of multiphasic screening and the development of sensitive parathormone assays have changed the demography and clinical symptomatology of patients presenting with primary hyperparathyroidism. This retrospective review includes 158 patients operated on for primary hyperparathyroidism at the Medical College of Georgia from 1973-1987. Compared to the 46 patients managed prior to 1973, the frequency of subclinical hyperparathyroidism has increased from 46% to 64%. The median patient age has increased from 50 to 59 years. Recognition of primary hyperparathyroidism in a more geriatric population modifies indications for surgical intervention in subclinical disease. Osteoporosis, myalgias, fatigue, arthralgias, memory loss, or constipation occurred in 50% of patients. These complaints are frequent in normocalcemic elderly people. They represent disease, not normal aging. Their exacerbation by hypercalcemia should not go uncorrected if neck exploration can be tolerated by the patient. PMID- 1431644 TI - Child abuse by scalding. AB - Physical abuse of children by burning is a serious crime that leaves the youngest of our children with permanent physical and emotional scars. The victims tends to be less than 2 years of age. Burn-abused children usually suffer from a spectrum of physical, psychologic, and nutritional neglect. Burn abuse is costly in terms of pain, suffering and health care. Up to 15% of acutely injured children seen in emergency departments, admitted or not, have been abused. Burns were involved in up to 22% of physical abuse cases. Up to 26% of pediatric burn admissions were the result of abuse. The most common form of burn abuse in children requiring hospitalization is the scald. Physicians who treat children and burn patients should have a knowledge of the literature and clinical factors associated with pediatric burn abuse. PMID- 1431645 TI - Of thankfulness. PMID- 1431646 TI - Long term care insurance: a vital component to estate preservation. PMID- 1431647 TI - Rethinking credentialing: preventing economic credentialing, data bank problems, and other troubles. PMID- 1431648 TI - Reporting confirmed positive HIV tests: an update. PMID- 1431649 TI - Guidelines for the physician-patient relationship. PMID- 1431650 TI - Time management: what it is, how it's done. PMID- 1431651 TI - Crisis in health care delivery--rescuing medicine from the clutches of government. PMID- 1431652 TI - Grady Memorial Hospital centennial: history and development, 1892-1992. PMID- 1431653 TI - The real revolution in medicine. PMID- 1431654 TI - Bruxism, neck pain, and a history of child sexual abuse. PMID- 1431655 TI - Introduction: the principle of solidarity in health care policy. PMID- 1431656 TI - The Human Genome Project and the social contract: a law policy approach. AB - For the first time in history, genetics will enable science to completely identify each human as genetically unique. Will this knowledge reinforce the trend for more individual liberties or will it create a 'brave new world'? A law policy approach to the problems raised by the human genome project shows how far our democratic institutions are from being the proper forum to discuss such issues. Because of the fears and anxiety raised in the population, and also because of its wide implications on the everyday life, the human genome analysis more than any other project needs to succeed in setting up such a social assessment. PMID- 1431657 TI - The right to genetic information: some reflections on Dutch developments. AB - New developments in genetics are rapidly spreading over the Western World. The standards of clinical practice differ however according to local value- and health-care systems. In this article a short survey is given of Dutch developments in this field. An effort is made to explain the philosophical and ethical background of Dutch policy by concentrating on autonomy, responsibility and the right not to know. PMID- 1431658 TI - Right not to know or duty to know? Prenatal screening for polycystic renal disease. AB - New dimensions in different ethical scenarios following genetic information require new medical-ethical Action Guides for physician-patient interaction. This paper discusses the ambiguity in moral choice between a "right not to know" and "a duty to know", regarding parental decision-making pro or contra selective abortion following prenatal screening for autosomal dominant polycystic kidney disease (Potter III) and related public policy issues. PMID- 1431659 TI - Techno-thanatology: moral consequences of introducing brain criteria for death. AB - This paper is based on the hypothesis that the effort to establish new criteria for diagnosing human death, which has been taking place over the past twenty years or more, can be viewed as a paradigm case for the impact of scientific and technological progress on morality. This impact takes the form of three tendencies within the change in morality, which may be characterized as 'denaturalization', 'functionalization' and 'homogenization'. The paper concludes with the view that these tendencies do not indicate a decline of morality, as feared by some authors, but rather a structural change. PMID- 1431660 TI - The medical exception: physicians, euthanasia and the Dutch criminal law. AB - The legalization of euthanasia, both in the Netherlands and in other countries is usually justified in reference to the right to autonomy of patients. Utilizing recent Dutch jurisprudence, this article intends to show that the judicial proceedings on euthanasia in the Netherlands have not so much enhanced the autonomy of patients, as the autonomy of the medical profession. PMID- 1431661 TI - Clinical ethics in assisting euthanasia: avoiding malpractice in drug application. AB - The debate on the ethical permissibility of euthanasia in medicine has a corollary in the ethical application of drugs. The overall moral limits of medical treatment apply evenly to the moral acceptability of the pharmacological aspect of the act of euthanasia. The pharmacological aspect of the act is of ethical importance not only for the person requesting an active ending of his or her life, but also for the grieving family. PMID- 1431662 TI - Criteria for death: self-determination and public policy. AB - 'Whole brain death' criteria have found support in Western cultures in regard to post-mortem organ donation and the termination of care for patients meeting these strict criteria. But they are of minimal use in Asian cultures and in the ethics of caring for the persistent vegetative patient. This paper introduces a formula for a global Uniform Determination of Death statute, based on the 'entire brain including brain stem' criteria as a default position, but allowing competent adults by means of advance directives to choose other criteria for determining death during the process of dying. PMID- 1431663 TI - Consensus and health policy in Hungary. PMID- 1431664 TI - Equity and solidarity: the context of health care in The Netherlands. AB - The current debate on health care resource allocation in the Netherlands is characterized by a social context in which two values are generally and traditionally accepted as being equally fundamental:solidarity and equity. We will present an outline of the distinctive features of the Dutch health care system, and analyze the present state of affairs in the resource allocation debate. The presuppositions of the political call for constraint and (renewed) government supervision and the role of the specific value context in recent proposals for reconstruction of the Dutch health care system will be evaluated. PMID- 1431665 TI - Principles, rules, duties, and babel: bioethics in the face of postmodernity. PMID- 1431666 TI - The method of 'principlism': a critique of the critique. AB - Several scholars have recently criticized the dominant emphasis upon mid-level principles in bioethics best exemplified by Beauchamp and Childress's Principles of Biomedical Ethics. In Part I of this essay, I assess the fairness and cogency of three broad criticisms raised against 'principlism' as an approach: (1) that principlism, as an exercise in applied ethics, is insufficiently attentive to the dialectical relations between ethical theory and mortal practice; (2) that principlism fails to offer a systematic account of the principles of non maleficence, beneficence, respect for autonomy, and justice; and (3) that principlism, as a version of moral pluralism, is fatally flawed by its theoretical agnosticism. While acknowledging that Beauchamp and Childress's reliance upon Ross's version of intuitionism is problematic, I conclude that the critics of principlism have failed to make a compelling case against its theoretical or practical adequacy as an ethical approach. In Part II, I assess the moral theory developed by Bernard Gert in Mortality: A New Justification of the Moral Rules, because Gert has recommended his approach as a systematic alternative to principlism. I judge Gert's theory to be seriously incomplete and, in contrast to principlism, unable to generate coherent conclusions about cases of active euthanasia and paternalism. PMID- 1431667 TI - Moving forward in bioethical theory: theories, cases, and specified principlism. AB - The field of bioethics has deployed different models of justification for particular moral judgments. The best known models are those of deductivism, casuistry, and principlism (under one, rather limited interpretation). Each of these models, however, has significant difficulties that are explored in this essay. An alternative model, suggested by the work of Henry Richardson, is presented. It is argued that specified principlism is the most promising model of justification in bioethics. PMID- 1431668 TI - Patients' duties. AB - This paper argues that patients' duties are derivable from the idea which typically grounds the idea of patients' rights: patient autonomy. The autonomous patient, joined in partnership with the health care professional, has self regarding obligations and obligations to others, including health care professionals. Patients' duties include, but are not limited to: a duty to be honest about why the patient seeks care; a duty to collect information on available treatments and likely side-effects; a duty for a patient who has an infectious condition to act on that information which can best prevent further transmission. PMID- 1431669 TI - Evaluation of the critical electron dose on the contractile activity of hydrated muscle fibers in the film-sealed environmental cell. AB - By using the film-sealed environmental cell (EC) having a liquid-injection function, we observed a contraction reaction of hydrated myofibrils isolated from crab muscle under the transmission electron microscope. Our purpose in this work was to evaluate the critical electron dose at which the hydrated fibers lose the contractile activity. The decision of whether the fibers contracted was done by the existence of contraction band after a contraction reaction. From the observations, it was concluded that its critical dose was 2 x 10(-4) C/cm2 or 12 electrons/nm2 at a protein level. PMID- 1431670 TI - Scanning and transmission electron microscopic studies on the upper and lower surfaces of the frog skin epidermal cells. AB - We examined the fine structure of the upper and lower surfaces of stratified squamous epithelial cells in the skin of frogs (Hyla japonica). SEM revealed the upper surface of superficial cells covered with ramified microridges (type 3). The width of the microridges was 0.20-0.24 microns. Microridges found at the cell boundary were about 0.30 microns in width and a narrow furrow was seen between the two cells. The numerous oval disk-like structures (0.23 x 0.32 microns in diameter) covered the lower surface of these superficial cells. The upper surface of cells in the 2nd layer was covered with baculiform or ramified microridges (type 2 or 3). On the cell boundary, two linear microridges (0.23-0.27 microns in width) were parallelly arranged. The width of the microridges covering the upper cell surface was 0.09-0.10 microns. Microvilli-like processes with a height of 0.32-0.37 microns were interspersed among the microridges. Their tip formed an oval plane (0.23 x 0.31 microns), which corresponded to the size of the disk-like structures on the lower surface of the superficial cells. Desmosomes were observed on the tip by TEM. These findings show that the disk-like structures on the lower surface of the superficial cells are the sites of binding with the microvilli-like processes on the upper surface of the 2nd layer cells. The disk like structures observed in the present study seem to be equivalent to the binding site on the upper surface of the surface cell layer of mammalian stratified squamous epithelium. PMID- 1431671 TI - Electron microscopic visualization of collagen aggregates without chemical staining. AB - Lateral, uni-directional aggregates of collagen, segment-long-spacing crystallites (SLS), were made by dialyzing collagen solutions against acetic acid containing ATP, and were examined by transmission electron microscopes without electron staining. There detected were at least 20 dark (electron dense) cross striations within SLS. The banding pattern was compared with the biochemical and biophysical properties of the amino acid side chains along the collagen molecule. The banding pattern of unstained SLS was mostly correlated with the intramolecular distribution of basic amino acid residues. Since basic amino acids have relatively large side chains, the distribution of mass (molecular weight of amino acids) along the molecule (local density profile) partially explained the cross-striation. Addition of fractions of molecular weight of ATP to basic residues made the local density profile much better correlate to the banding pattern. We conclude that the electron microscopic banding pattern of unstained SLS was generated by the local amount of material or local density profile along the collagen aggregates, which was enhanced by ATP bound to positively charged basic residues. The concept that the electron density correlates with the amount of material is fundamental in electron microscopy, and it has been proven with biological materials in this paper. PMID- 1431672 TI - Effect of hydrogen peroxide on mammalian chromatin: electron microscopic studies. AB - Chromatins purified from rat liver as well as from cultured Chinese hamster V79 cells were treated with hydrogen peroxide in presence of iron in vitro. When examined in a transmission electron microscope, chromatins from both the sources were found to lose the native morphology. There were evidences of aggregation of the chromatin fibers. This could be due to DNA-protein and DNA interstrand crosslinking induced by Fenton reaction. PMID- 1431673 TI - Multivariate statistical analysis of electron micrographs of a mammalian transcription initiation complex. AB - We describe the appearance of the murine ribosomal protein (rp) L32 gene transcription initiation complex as determined by electron image analysis. Using a fractionated nuclear extract enriched for transcription factors necessary for rpL32 gene transcription in vitro and a DNA fragment containing the rpL32 gene promoter, the transcription initiation complex was prepared and viewed by standard transmission electron microscopy. Image analysis demonstrated that the complex was a multilobed structure. PMID- 1431674 TI - Chemical signalling systems: the rules of the game. PMID- 1431675 TI - Effects of basic fibroblast growth factor, transforming growth factor-beta and nerve growth factor on the secretory function of the bovine corpus luteum in vitro. AB - The effects were investigated of basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta) and nerve growth factor (NGF) on the release of progesterone and oxytocin from the bovine corpus luteum (CL) at different stages of the oestrous cycle. A microdialysis system (MDS) of CL and a cell culture system with a reduced number of endothelial cells were used. In the MDS of CL from the mid-luteal stage (days 8-12 of the oestrous cycle), infusion with bFGF (0.1, 1, 10 and 100 ng/ml), TGF-beta (0.1, 1 and 10 ng/ml) and NGF (0.1, 1, 10 and 100 ng/ml) for 30 min induced significant acute effects on the release of progesterone. Both bFGF and NGF stimulated the release of progesterone during peptide infusion, TGF-beta and also bFGF in the period thereafter. This stimulation was dose-dependent during and after the infusion only for bFGF. This response pattern was observed at all luteal stages for the three growth factors, but bFGF was more stimulatory at the early (days 5-7) and mid-luteal stages during and after peptide infusion. The release of oxytocin was stimulated by bFGF in a dose-dependent manner. At the highest dose, bFGF, TGF-beta and NGF stimulated the release of oxytocin throughout all three luteal stages. When luteal cells were cultured with growth factors, only TGF-beta showed a dose dependent inhibition of both basal and LH-stimulated progesterone as well as oxytocin release (measured between 48 and 52 h of culture). NGF had an inhibitory effect only on the basal release of oxytocin. bFGF had no effect on the release of either hormone under continuous stimulation in cell culture. The results indicate that bFGF, TGF-beta and NGF act directly and acutely on the secretory function of bovine CL in the MDS but also have long-term effects as shown in cell culture. bFGF appears to be an important autocrine/paracrine regulator of CL function, since local expression of its mRNA, peptide synthesis and its mitogenic and non-mitogenic actions have now been confirmed. Endothelial cells from the CL have been identified as target cells for bFGF. Differences observed between the two systems might thus be attributed to the presence or absence of cell-to-cell contact and a reduced number of endothelial cells, as well as to the duration of peptide stimulation and medium changes every 24 h compared with the flow-through conditions in the MDS. PMID- 1431676 TI - Effects of tri-iodothyronine and insulin-like growth factor-I (IGF-I) on alkaline phosphatase activity, [3H]thymidine incorporation and IGF-I receptor mRNA in cultured rat epiphyseal chondrocytes. AB - The effects of tri-iodothyronine (T3) and insulin-like growth factor-I (IGF-I) on [3H]thymidine incorporation, alkaline phosphatase (ALP) activity and IGF-I receptor mRNA levels were studied in rat epiphyseal chondrocytes cultured in monolayer. Chondrocytes from enzymatically digested rat tibia epiphyseal growth plates were seeded in monolayer culture and precultured for 7-14 days in Ham's F 12 medium supplemented with 10% (v/v) newborn calf serum and 1% (v/v) of a serum substitute. After preculture the medium was changed to Ham's F-12 medium containing 1% (v/v) serum from hypophysectomized rats, and the effects of T3 and/or IGF-I on DNA synthesis ([3H]thymidine incorporation), ALP activity (a late marker of differentiated epiphyseal chondrocytes) and IGF-I receptor mRNA levels were studied. ALP activity was increased by T3 in a dose-dependent manner with a maximal response at 10 micrograms T3/l (678 +/- 86% compared with control culture). The increase in ALP activity was accompanied by a concomitant decrease in [3H]thymidine incorporation (52 +/- 14% compared with control culture). Human GH (hGH; 50 micrograms/l) and IGF-I (25 micrograms/l) had no stimulatory effect on ALP activity. However IGF-I (10 micrograms/l) exerted an inhibition on the T3 (10 micrograms/l)-induced increase in ALP activity (64 +/- 9% compared with T3 treated culture). T3 (3 micrograms/l) inhibited the increase in [3H]thymidine incorporation caused by 25 micrograms IGF-I/l (51 +/- 13% compared with IGF-I treated culture). Furthermore, IGF-I receptor mRNA levels were increased by 10 micrograms T3/l (137 +/- 4.2% compared with control culture) while no effect of hGH (50 micrograms/l) or IGF-I (25 micrograms/l) was demonstrated. Both T3 and IGF-I were shown to interact with epiphyseal chondrocytes and both substances seemed to affect cell proliferation and maturation and therefore longitudinal bone growth. Furthermore, the results indicated that IGF-I is important for proliferation of the cells while T3 initiates the terminal differentiation of epiphyseal chondrocytes. PMID- 1431678 TI - Carbachol increases intracellular free calcium concentrations in human granulosa lutein cells. AB - We investigated whether the stimulation of human granulosa-lutein cells with muscarinic and nicotinic receptor agonists can cause increases in intracellular free calcium (Ca2+), using Fura-2 microfluorimetry. The addition of carbachol (a non-selective muscarinic and nicotinic receptor agonist) to cultured human granulosa-lutein cells increased intracellular free Ca2+ levels. Concentrations as low as 10 nmol/l were effective. In contrast, nicotine did not evoke elevations of intracellular free Ca2+. Basal Ca2+ levels ranged around 70-140 nmol/l and maximal, carbachol-induced peaks reached 1.1 mumol/l. The carbachol induced Ca2+ signal was abolished after preincubation of the cells with the muscarinic receptor antagonists quinuclidinyl benzilate or atropine, but it was not affected by removal of extracellular Ca2+. Further evidence for the involvement of intracellular Ca2+ stores is provided by experiments in the absence of extracellular Ca2+. While thapsigargin (a blocker of ATP-driven Ca2+ uptake by intracellular stores) and ionomycin (an ionophore by which Ca2+ is released from intracellular stores) evoked small Ca2+ transients, cells pretreated with these agents did not respond to carbachol any more. These data suggest the presence of a functional muscarinic receptor on human granulosa lutein cells and imply the involvement of intracellular Ca2+ stores during the cellular response. These results also suggest the participation of the nervous system, acting through muscarinic receptors, in the control of the function of human granulosa-lutein cells. PMID- 1431677 TI - Glycyrrhizin induces mineralocorticoid activity through alterations in cortisol metabolism in the human kidney. AB - It has been suggested that the mineralocorticoid action of glycyrrhizin is caused by a defect in the conversion of cortisol to cortisone through inhibition of the enzyme 11 beta-dehydrogenase (11 beta-DH). We investigated the functional significance of the inhibition of this enzyme as a mechanism of the mineralocorticoid action of glycyrrhizin. Eighteen healthy volunteers were divided into three groups of six and treated as follows: (1) 225 mg glycyrrhizin/day, (2) 0.1 mg 9 alpha-fluorocortisol (FC)/day and (3) 225 mg glycyrrhizin and 1.5 mg dexamethasone/day, all of which were given for 7 days. The administration of glycyrrhizin or FC induced a similar mineralocorticoid effect; specifically, suppression of plasma renin activity, hypokalaemia and kaliuresis. During the concomitant administration of glycyrrhizin and dexamethasone, however, these mineralocorticoid effects were significantly attenuated. During the administration of glycyrrhizin, urinary excretion of cortisol increased without change in the plasma levels of cortisol, while both plasma level and urinary excretion of cortisone decreased. Changes in cortisol metabolism were not observed during the administration of FC. These results demonstrated the functional significance of the inhibition of 11 beta-DH in the mineralocorticoid activity of glycyrrhizin in man. PMID- 1431679 TI - Influence of ovarian steroids on myometrial sensitivity and tolerance to relaxin in the rat in vivo: lack of cross-tolerance between relaxin, salbutamol and cromakalim. AB - The influence of oestradiol benzoate and progesterone on uterine sensitivity and development of tolerance to relaxin was investigated in bilaterally ovariectomized non-pregnant rats in vivo. Bolus doses of relaxin (2-20 micrograms/kg i.v.) produced rapid and reversible inhibition of uterine contractions in a dose-dependent manner. Treatment with oestradiol benzoate or oestradiol benzoate plus progesterone significantly increased uterine sensitivity to relaxin over 48 h by 2.4- to 8.5-fold. Tolerance to relaxin developed during continuous infusion of the hormone at 20 micrograms/kg per h for 40 h. A 7.8- to 17.4-fold reduction in sensitivity to relaxin was observed in relaxin-infused rats, whereas no change in sensitivity was observed in saline-infused rats. Infusion of relaxin at 50 micrograms/kg per h for 40 h produced a 131.8-fold reduction in uterine sensitivity to relaxin. The uterus remained tolerant to relaxin for up to 24 h after cessation of infusion. Treatment with oestradiol benzoate and/or progesterone did not influence the extent of tolerance development, but a more rapid recovery of uterine sensitivity to relaxin was observed in rats treated with oestradiol benzoate plus progesterone. Cross tolerance with other uterine relaxant drugs was measured to investigate possible common mechanisms of action and sites of tolerance between relaxin and a beta adrenoceptor agonist (salbutamol) and potassium channel openers (cromakalim and minoxidil sulphate). No cross-tolerance was observed between relaxin and salbutamol, or relaxin and cromakalim or minoxidil sulphate. Cross-tolerance between cromakalim and minoxidil sulphate was seen. PMID- 1431680 TI - Interaction between myometrial relaxants and oxytocin: a comparison between relaxin, cromakalim and salbutamol. AB - The influence of treatment with oestradiol on the effects of the uterine relaxants, relaxin, salbutamol (an agonist at beta 2-adrenoceptors) and cromakalim (a potassium channel opener) and their interactions with the uterine stimulant oxytocin were investigated in vivo in the ovariectomized rat. Oestradiol benzoate (0.4 micrograms/kg per day) significantly increased sensitivity to cromakalim as an inhibitor of spontaneous uterine contractions compared with vehicle-treated rats by approximately threefold. The same dose of oestradiol benzoate had no effect on uterine sensitivity to salbutamol. Previous studies have shown that this dose of oestradiol benzoate produces a twofold increase in uterine sensitivity to relaxin as an inhibitor of spontaneous contractions. Oestradiol influenced the ability of relaxin to inhibit oxytocin stimulated uterine contractions. In corn oil-treated rats, uterine responses to relaxin were markedly reduced during oxytocin infusion compared with responses to relaxin before oxytocin; the maximum obtainable response to relaxin was less than 50% inhibition. In oestradiol-treated rats, uterine sensitivity to relaxin during oxytocin infusion was similar to that observed against spontaneous contractions. Cromakalim was able to inhibit uterine contractions during oxytocin infusion in both corn oil- and oestradiol-treated rats, uterine sensitivity to cromakalim being similar in the absence and presence of oxytocin for both hormone treatment groups. Salbutamol was also able to inhibit uterine contractions during oxytocin infusion in both corn oil- and oestradiol-treated rats. Oestradiol treatment increased the potency of salbutamol as an inhibitor of oxytocin-stimulated uterine contractions compared with corn oil treatment by 3.5-fold. The interaction of oestradiol and relaxin during late pregnancy may be important for attenuation of the myometrial response to stimulants. PMID- 1431681 TI - Relationship between the resting metabolic rate and hepatic metabolism in rats: effect of hyperthyroidism and fasting for 24 hours. AB - We have examined the relationship between the changes in resting metabolic rate (RMR) and those in hepatic metabolism induced by hyperthyroidism and fasting for 24 h. We found that hyperthyroidism induced a significant increase in RMR, while fasting for 24 h reduced RMR in euthyroid but not in hyperthyroid rats. We have also measured oxygen consumption in isolated hepatocytes from euthyroid and hyperthyroid rats, fed or fasted for 24 h. Hyperthyroidism induced an increase in oxygen consumption in rat liver cells; fasting for 24 h increased respiratory rates in isolated liver cells from euthyroid but not from hyperthyroid rats. The findings showed that hyperthyroidism and fasting for 24 h have opposite effects on RMR but similar effects on hepatic metabolism. The results also indicated that the increase in RMR found in hyperthyroid rats is partly due to an increase in hepatic metabolism, while no correlation exists between variations in resting and hepatic metabolism induced by 24-h fasting. PMID- 1431682 TI - Specific binding sites for 125I-labelled epidermal growth factor in the ovine corpus luteum and human placenta. AB - Specific, high-affinity binding sites for radiolabelled mouse epidermal growth factor (mEGF) were demonstrated in homogenates and membranes of ovine corpora lutea. Subcellular fractionation on sucrose density gradients demonstrated that luteal EGF receptors were associated with fractions enriched in cell surface membrane markers. Binding of 125I-labelled mEGF to ovine luteal EGF receptors was dependent on the pH, temperature and duration of incubation, and on the concentration of metal ions present in the incubation medium. Unlabelled mEGF and human EGF (urogastrone) competed for the binding of radiolabelled mEGF to ovine luteal homogenates at low doses (half-maximal inhibition of binding (IC50) at 2-3 nmol/l). Transforming growth factor-alpha also competed for mEGF-binding sites (IC50, 4-10 nmol/l), but a range of peptides, growth factors and protein hormones were ineffective at much higher concentrations. Concave Scatchard plots for 125I labelled EGF binding and Hill coefficients of < 1 for displacement radiolabelled EGF suggested negative co-operativity of binding sites, and dilution at equilibrium accelerated the rate of dissociation of 125I-labelled EGF from human placental (but not from ovine luteal) receptors. Specific EGF-binding sites were also demonstrated in rat and rabbit placental homogenates, and in luteal homogenates of the pig. Luteal concentrations of EGF receptors appeared to be reduced significantly during early pregnancy in both the pig and sheep. PMID- 1431683 TI - 11 beta-Hydroxysteroid dehydrogenase in the rat ovary: high expression in the oocyte. AB - The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the conversion of physiological glucocorticoids to inactive products, thus modifying the access of glucocorticoids to glucocorticoid and mineralocorticoid receptors. Glucocorticoids may affect ovarian function both indirectly and via binding to ovarian receptors. We have demonstrated 11 beta-HSD bioactivity and mRNA expression in rat ovary in vitro. The enzyme was localized to oocytes and luteal bodies immunohistochemically using two antibodies raised against purified rat liver 11 beta-HSD. These data are supported by in-situ hybridization studies, which also localized 11 beta-HSD mRNA expression to oocytes and luteal bodies. The results suggest that 11 beta-HSD may modulate the effects of glucocorticoid on ovarian function. PMID- 1431684 TI - Growth hormone promotes early initiation of hepatocyte growth factor gene expression in the liver of hypophysectomized rats after partial hepatectomy. AB - GH accelerates hepatic regeneration in the rat. Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, is considered to be a major regulator of hepatic regeneration. In the present study, the effects of GH and insulin-like growth factor-I (IGF-I) on HGF gene expression in regenerating rat liver was investigated. In hypophysectomized rats treated with GH, hepatic HGF mRNA levels were increased 3 h after partial hepatectomy and reached peak levels after 5 h. In rats with intact pituitaries and in hypophysectomized rats not given GH treatment, HGF mRNA levels in liver were unchanged during the first 5 h following hepatectomy and reached peak levels after 10-18 h. DNA synthesis in the liver of GH-treated rats increased from low levels 10 h after hepatectomy to peak levels after 18 h. In rats without GH treatment the synthesis of DNA was still low 18 h after hepatectomy and was increased after 26 h. Treatment of hypophysectomized rats with IGF-I promoted increases in hepatic HGF mRNA levels and DNA synthesis 3.5 h and 15 h after hepatectomy respectively. HGF mRNA levels were constantly lower after sham-hepatectomy than after partial hepatectomy. In summary, in hypophysectomized rats the responses of hepatic HGF gene expression and DNA synthesis to partial hepatectomy were both accelerated by treatment with GH or IGF-I. PMID- 1431685 TI - Activation of the hypothalamo-pituitary-adrenocortical axis in the conscious rabbit by the pyrogen polyinosinic:polycytidylic acid is dependent on corticotrophin-releasing factor-41. AB - The pyrogenic interferon inducer polyinosinic:polycytidylic acid (Poly I:C) was shown to activate the rabbit hypothalamo-pituitary-adrenocortical (HPA) axis in vivo. The immunoreactive cortisol response to Poly I:C (2.5 micrograms/kg) was shown to have a corticotrophin-releasing factor-41 (CRF-41)-dependent component which was abolished by peripheral immunoneutralization using an anti-CRF-41 monoclonal antibody (KCHMB001; 2.5 mg/kg i.v.). Peripheral administration of the arginine vasopressin (AVP) V1 receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin; 225 nmol/kg i.v.) had no effect on the response of immunoreactive cortisol to Poly I:C, suggesting that AVP was not involved in activation of the HPA axis. Poly I:C increased both body temperature and circulating immunoreactive prostaglandin E2; these responses were abolished by the cyclo-oxygenase inhibitor ketoprofen (3 mg/kg s.c.). The immunoreactive cortisol response to Poly I:C, however, remained after the administration of ketoprofen, indicating a prostaglandin (PG)-independent component. The immunoreactive cortisol levels in control, saline vehicle-treated, animals were reduced by both the CRF-41 receptor antagonist (alpha-helical CRF (9-41); 6.25 nmol/kg i.v.) and ketoprofen (3 mg/kg s.c.) indicating that this basal state is dependent on both CRF-41 and PGs. PMID- 1431686 TI - Epidermal growth factor concentrations in pig tissues and body fluids measured using a homologous radioimmunoassay. AB - A homologous radioimmunoassay for the measurement of epidermal growth factor (EGF) levels in pig tissues and body fluids has been developed using an antiserum to recombinant porcine EGF. The assay is highly specific, showing no cross reactivity with a variety of other polypeptides including the structurally related protein, transforming growth factor-alpha. Furthermore, < 1% cross reactivity was observed with mouse EGF emphasizing the necessity for homologous assays for EGF measurement. Immunoreactive EGF was present in extracts of pig kidney and pancreas (3.44 +/- 0.43 and 0.76 +/- 0.13 (S.E.M.) pmol/g wet weight respectively), but was not detected in extracts of submaxillary gland or liver. Although immunoreactive EGF was not detectable in uterine, allantoic or ovarian follicular fluids, colostrum contained EGF at biologically active concentrations (0.84 +/- 0.15 nmol/l). Immunoreactive EGF was also present in pig urine, with similar concentrations in samples from male or female animals. In addition, pig urine inhibited the binding of 125I-labelled EGF to 3T3 fibroblasts and stimulated DNA synthesis in quiescent monolayers of these cells, indicating that the immunoreactive material in urine is biologically active. Quantitative comparisons of the data presented here with that published previously indicate considerable species variation in the EGF levels of various tissues and body fluids. PMID- 1431687 TI - Salivary insulin-like growth factor-I originates from local synthesis. AB - Insulin-like growth factor-I (IGF-I) is a GH-dependent growth factor found in its highest concentrations in plasma. It is also measurable in saliva. The origins of salivary IGF-I concentrations were studied. Intracardial administration of Sprague-Dawley rats with 125I-labelled IGF-I and subsequent analysis of plasma and saliva samples by exclusion gel chromatography and SDS-PAGE, followed by autoradiography, demonstrated the apparent inability of IGF-I to cross from the plasma pool through to saliva. 125I-Labelled IGF-I was not chromatographed immediately before injection, resulting in administration of free iodide along with the iodinated peptide. This free iodide was demonstrable in saliva, indicating that movement of substances from plasma to saliva was measurable using the levels of 125I activity administered. Free iodide in saliva was not contributed to by 125I-labelled IGF-I degradation since 125I-labelled IGF-I was shown to be stable in saliva over 24 h. These data indicated that IGF-I in saliva is produced locally. Identification of a 4.7 kb IGF-I mRNA transcript in rat parotid salivary gland was consistent with IGF-I synthesis within that tissue. PMID- 1431688 TI - Fluid balance, electrolyte profiles and plasma parathyroid hormone concentrations in ewes treated with epidermal growth factor. AB - The infusion of low doses of epidermal growth factor (EGF) into lactating ewes stimulates water intake and urine volume. The plasma concentrations and daily output of various electrolytes in milk and urine are also affected. We have investigated this further by recording the effects of EGF infusion on fluid balance, electrolyte profiles and plasma concentrations of glucose and parathyroid hormone (PTH) in non-pregnant, non-lactating ewes. Twenty-four animals (n = 8 per group) received infusions of 100 ml saline/day into the jugular vein for 10 days (days 1-10) followed by EGF at a dose rate of either 1 (low dose), 5 (medium dose) or 10 (high dose) micrograms/kg liveweight per day in 100 ml saline for 5 days (days 11-15). All ewes then received an infusion of 100 ml saline/day for 10 days (days 16-25). Most plasma and urine samples had undetectable concentrations of EGF-immunoreactive material during the periods of saline infusion. During EGF infusion, the highest amounts of EGF infusate excreted in urine were 1.6, 5.9 and 5.6% for ewes in low, medium and high dose groups respectively. Water intake increased by 17% (0.5 kg), 88% (2.5 kg) and 89% (2.3 kg) and urine volume increased by 29% (0.5 kg), 108% (2.2 kg) and 134% (2.1 kg) for the three groups respectively. Fluid balance and feed intake were not affected by EGF infusion, but the output of faecal dry matter was reduced in ewes receiving the two higher doses of EGF. All levels of EGF resulted in hypocalcaemia, increased plasma PTH concentrations and hypermagnesaemia. There was no effect of EGF on plasma concentrations of K+ and glucose or on daily urinary excretion of K+ and Mg2+. The only response to the low dose was a reduced plasma concentration of Na+ and an increased daily urinary urate excretion. The two higher doses increased the daily urinary excretion of Na+, PO4(3-) and urate, but had no effect on the respective concentrations in plasma. Urinary Ca2+ excretion was reduced only during infusion of the medium dose of EGF. The responses of most variables were similar during infusion of the medium and high doses of EGF. All three doses of EGF induced polydipsic and diuretic responses in ewes, and infusions of 5-10 micrograms EGF/kg liveweight per day affected renal excretion of Ca2+, Na+ and PO4(3-). We interpret the responses of the kidney and plasma PTH concentrations as a means of maintaining the homeostasis of plasma profiles of electrolytes. PMID- 1431690 TI - Intracanal placement of Ca(OH)2: a comparison of techniques. AB - Ten extracted human maxillary first molars were selected with a variety of root curvatures. The distofacial roots were resected and the mesiofacial canals were instrumented to a size #25 K file. Three techniques were used to introduce Ca(OH)2 paste into the instrumented canals. These techniques were evaluated for their ability to carry the Ca(OH)2 to working length and also to produce a dense fill. The Lentulo spiral was most effective in carrying the paste to working length. The Lentulo spiral also produced the highest quality fill. The Calasept injection system followed by a #25 finger plugger was the second most effective technique. Counterclockwise rotation of a #25 K file was the least effective of the techniques tested. PMID- 1431689 TI - Effect of different sealers on thermoplasticized Gutta-percha root canal obturations. AB - The objective of this study was to test the hypothesis that the apical seal provided by thermoplasticized root canal obturations depends on the film thickness of the sealer used. The root canals of 120 maxillary cuspid teeth were instrumented and divided into six equal groups of 20 teeth. A thermoplasticized gutta-percha root canal obturator was used to make an impression of the lubricated canal and coated with a sealer cement before reseating. Five different sealer cements of known film thickness were studied. They were, in the decreasing order of film thickness, Roth's Type I Cement, Seal-apex, Lee Endofil, AH26, and Ketac-Cem. The control group that received no sealer was prepared as recommended by the manufacturer. The degree of microleakage was based on the depth of dye penetration from the apical end measured by two independent examiners. The data collected were analyzed by analysis of variance and Weibull distribution. Analysis of variance shows that the control group exhibited significantly higher dye penetration depth (p < 0.05) while there were no significant differences among the other five groups. Analysis by Weibull distribution function shows that Lee Endofil and AH26 exhibited a higher percentage of lower linear dye penetration values compared with other groups. PMID- 1431691 TI - Effects of Nd:YAG laser on apical seal of teeth after apicoectomy and retrofill. AB - The application of Nd:YAG laser to tooth surface can change its surface permeability. The purpose of this study was to investigate the effects of Nd:YAG laser on the permeability of dentin following apicoectomy and retrofill. Sixty single-rooted teeth were randomly assigned to six groups of 10 teeth each. The six groups were arranged in three pairs, experimental and control groups. The canals of teeth in pairs 1 and 2 were cleaned, shaped, obturated, and their apical 2 mm were resected. A class I preparation was prepared and filled with amalgam in each tooth in pair 1. The apical 2 mm of each tooth in pair 3 was removed, and a class I preparation was prepared and filled with amalgam. The apical surface of resected roots in half of the samples in each pair was lased twice by using Nd:YAG laser. The duration of lasing and the number of pulses were recorded for each tooth. After application of nail polish to the unoperated surface of each tooth, the teeth were placed in 0.5% methylene blue dye for 48 h. The amount of dye penetration in sagittal sections of each tooth was measured. The amount of dye penetration was significantly lower in lased roots than in nonlased ones (p < 0.05). Based on our results, it appears that application of Nd:YAG laser reduces the permeability of resected roots. PMID- 1431692 TI - Evaluation of internal sealing ability of three materials. AB - Thirty-six maxillary central incisors were prepared in a manner similar to nonvital bleaching procedures. They were examined with respect to the degree of procion green dye penetration of dentin with and without heating. Cavit, IRM, and zinc phosphate cement were used to evaluate their sealing ability. Cavit and IRM provided better internal sealing of the dentin than did zinc phosphate cement. PMID- 1431693 TI - Torsional testing of Canal Master U hand instruments. AB - Ten each of size 25, 30, 35, 40, and 45 Canal Master U hand instruments were tested for torsional failure and revolutions to failure. In addition, the point at which separation occurred was measured on the instrument shaft. An Instron 1125 machine was used for all torsion testing. The mean torque failure value for size 25 and 35 Canal Master U instruments exceeded the ADA specification No. 28 minimum values while sizes 30, 40, and 45 were below the ADA minimum average values. All Canal Master U averages for revolutions to failure exceeded the ADA minimums. Although size 25 was above the minimum average, due to a wide range of values, 5 of the 10 were below the ADA specification No. 28 values. The point of instrument separation was 0.325 to 1.575 mm behind the cutting head. Due to the structural design differences of endodontic files versus Canal Master U, it is suggested that an additional category of ADA specification be introduced for Canal Master endodontic instruments. PMID- 1431694 TI - The mental foramen: 3. Size and position on panoramic radiographs. AB - Panoramic radiographs were made of 75 dry, adult human mandibles. The size and position of the mental foramen in relation to the second premolar was determined. The mental foramen on panographic radiographs was slightly larger than reported on periapical radiographs. The average position of the foramen was mesial and below the radiographic apex of the tooth. Panoramic radiography may account for a distal shift of the foramen and a 23% increase in size of the mandibles examined. PMID- 1431695 TI - Long-term evaluation of surgically placed amalgam fillings. AB - The coauthors of this article had developed the clinical impression that whereas surgically placed amalgam fillings are successful on a short-term basis, the long term prognosis for these cases may not be nearly as favorable. In order to test this hypothesis, as many patients as could be contacted, either directly or indirectly, who had been treated before 1981 were evaluated. Excluded from this study were cases for which failure could be attributed to any reason other than failure from the amalgam reverse filling. Therefore, all cases included had to demonstrate periapical healing prior to ultimate breakdown. On this basis, 60 of 104 teeth (57.7%) were considered to be successful and 44 teeth (42.3%) were determined to be failures. PMID- 1431696 TI - Periodontal changes following coronal/root perforation and formocresol pulpotomy. AB - A clinical case report is presented which describes the sequelae of an iatrogenic lateral crown/root perforation and a formocresol pulpotomy. The post-operative course of the initial therapy included significant hard and soft tissue destruction and eventual tooth loss. The possible implication of the role of formocresol is discussed. PMID- 1431697 TI - Assessment of evidence versus consensus or prejudice. PMID- 1431699 TI - The Epping jaundice outbreak: a 24 year follow up. AB - STUDY OBJECTIVE: The aim was to trace 84 cases of jaundice that occurred following accidental ingestion of methylene dianiline (MDA) in Epping in 1965, and to look at long term health effects. DESIGN: The original case notes of the cases were used to identify the patients. Subsequent tracing procedures included local general practitioners, the Central NHS Registry, electoral rolls, and company records. SETTING: This was a community based survey. MAIN RESULTS: The health status of 68 (81%) of the group was established with 18 deaths. Of the 50 cases known to be alive, 58% completed a health questionnaire. The causes of death were unremarkable except for one case of carcinoma of the biliary tract. Two surviving cases had suffered retinal pathology. Four other surviving cases had had a further, perhaps unrelated, episode of jaundice. CONCLUSIONS: Although the dose and route of administration in the epidemic differed from occupational exposure, this follow up study a generation on provides little, if any, evidence of long term health sequelae. Nevertheless, in the absence of well documented exposure and health effects data, such accidental poisonings with proven animal carcinogens warrant long term follow up. The identified cohort will be the subject of further study. PMID- 1431698 TI - Evaluating prognostic factors: implications for measurement of health care outcome. PMID- 1431700 TI - Auditing and improving notification and chemoprophylaxis in bacterial meningitis. AB - STUDY OBJECTIVE: The aim was to audit, against agreed standards, the control of bacterial meningitis, in particular completeness of notification and appropriateness of distribution of chemoprophylaxis to contacts; and to implement appropriate changes and monitor their impact. DESIGN: The first phase involved determination, for the years 1983 and 1984, of completeness of notification by comparison with a comprehensive case register. Information about chemoprophylaxis was obtained from case notes, questionnaires to general practitioners and other records. The second phase involved introducing a programme of clinician education in the hospital with the poorest observed notification performance and re examining performance during 1988. Districtwide education regarding chemoprophylaxis was undertaken and the situation re-examined in 1988. SETTING: The study took place in Mid Glamorgan Health Authority (population 536,000), with four acute hospitals. POPULATION: Consisted of all the residents of Mid Glamorgan Health Authority. MAIN RESULTS: During the first phase of the audit only 28 out of 79 cases of bacterial meningitis were notified (35%). Performance in one hospital was significantly worse than in the other three. Chemoprophylaxis was distributed to 20 out of 26 (77%) cases of meningococcal meningitis but inappropriate drugs were used in four cases and prophylaxis was distributed more widely than is recommended in 10 cases. In the phase 2 re-examination, a significant improvement in notification was observed in the hospital where special measures were taken, with no change in a "control" hospital. Chemoprophylaxis improved throughout the District, although rifampicin continued to be distributed too widely. CONCLUSIONS: As a result of this audit, measurable improvements in both infectious disease notification and chemoprophylaxis practice were obtained by the education of clinicians. The study provides a good example of a completed audit cycle in public health medicine. PMID- 1431701 TI - Bacteriological survey of tuberculous lymphadenitis in southeast England, 1981 1989. AB - STUDY OBJECTIVE: The aim was to detect any changing trends in the nature and incidence of tuberculous lymphadenitis in southeast England and to determine whether there is any evidence for an increase in this disease that could be related to HIV infection. DESIGN: Mycobacteria isolated from patients with lymphadenitis in the years 1981 to 1989 were identified. Information was available on the age, sex, and ethnic origin of the patients and the anatomical site from which the mycobacterium was isolated. SETTING: The Public Health Laboratory Service Regional Tuberculosis Centre at Dulwich, which receives over 95% of mycobacteria isolated in southeast England. MAIN RESULTS: From 1980 to 1989, cultures were received from 1817 patients with mycobacterial lymphadenitis: 1677 were M tuberculosis, 25 M bovis, 21 M africanum, and 94 were other (environmental) species. In comparison with a survey conducted in the same region in 1973-80, the number of ethnic Indian subcontinent patients with lymphadenitis due to M tuberculosis had dropped by 30% and the number of European patients had dropped by 43% and showed a continuing decline and a shift towards an older age group. By contrast, there was a 20% increase in the number of cases due to environmental mycobacteria. The number of species causing such infections had increased and a greater proportion of patients were adults. Three patients infected by environmental mycobacteria were known to be HIV positive. CONCLUSIONS: The incidence of lymphadentis due to M tuberculosis is declining but cases due to environmental mycobacteria are increasing, with a greater diversity of species and more adult patients. There is no conclusive evidence for an impact of HIV infection on the incidence and nature of mycobacterial lymphadenopathy in southeast England, but this cannot be ruled out. PMID- 1431702 TI - The Thule episode epidemiological follow up after the crash of a B-52 bomber in Greenland: registry linkage, mortality, hospital admissions. AB - STUDY OBJECTIVES: The aim was to explore the pattern of disease in staff associated with a bomber that crashed in 1968 when carrying nuclear bombs. DESIGN: The database was constructed from staff files of Danish workers employed from 1 April 1963 to 1 July 1971. Comparison was made between subsequent mortality and hospital admissions of workers employed during the clean up of the crashed bomber, and those employed outside this period. SETTING: The study involved workers employed at Thule US air base in Greenland. MAIN RESULTS: During 1963-1971, 4322 staff were employed at the air base. Of these, 4265 (98.7%) were identified in 1987, among whom 1202 workers were employed during the clean up period. No differences were found in total mortality, or mortality from cancer, heart disease, or accidents, after allowing for differences in age, marital status, or length of employment, between those employed during the clean up period and those employed at other times. Similarly, no difference in hospital admissions between the two groups was found. CONCLUSIONS: No harmful effects on health due to the crash were found, as measured by mortality and hospital admissions. PMID- 1431703 TI - Symptomatology of children in contact with sea water contaminated with sewage. AB - STUDY OBJECTIVE: The aim was to determine whether or not there was a measurable risk of ill health associated with contact with sea water for children between the ages of 6 and 11 years old. DESIGN AND SETTING: This was a prospective survey carried out on Blackpool beach. Parents of children between the ages of 6 and 11 years were interviewed over a seven week period during July, August, and September, 1990. Respondents were followed up 10-14 d after the original interview by either telephone or post. Water samples were collected on each day of the survey. PARTICIPANTS: 939 interviews with parents or guardians were completed on the beach; 857 (91.9%) of these persons agreed to a follow up interview. The results of this study are based on 703 cases of matched data, of good quality, collected for each child on the beach and during a follow up interview. MAIN RESULTS: Non-compliance with the European Community microbiological imperative standards for recreational waters at Blackpool Tower and South Pier sampling sites, respectively, ranged between: 6% and 7% for total coliforms; 13% and 25% for faecal coliforms; 69% and 80% for faecal streptococci (Guide standard); 50% and 67% for salmonellae and 73% and 88% for enteroviruses. There was a significant overall increase in the mean number of symptoms reported for each child (p < 0.001). However, the prevalence of certain symptoms increased significantly only in those children who had been in contact with the water on the day of the beach interview. These symptoms included vomiting (p < 0.0009), diarrhoea (p < 0.0001), itchy skin (p < 0.0009), fever (p < 0.0013), lack of energy (p < 0.0007), and loss of appetite (p < 0.0227). None of the other variables investigated could account for the significant increase in the reported symptom experience of those children in contact with sea water contaminated with sewage. CONCLUSIONS: Children who come into contact with contaminated sea water are likely to develop symptoms as a result. PMID- 1431704 TI - The Small Area Health Statistics Unit: a national facility for investigating health around point sources of environmental pollution in the United Kingdom. AB - STUDY OBJECTIVE: The Small Area Health Statistics Unit (SAHSU) was established at the London School of Hygiene and Tropical Medicine in response to a recommendation of the enquiry into the increased incidence of childhood leukaemia near Sellafield, the nuclear reprocessing plant in West Cumbria. The aim of this paper was to describe the Unit's methods for the investigation of health around point sources of environmental pollution in the United Kingdom. DESIGN: Routine data currently including deaths and cancer registrations are held in a large national database which uses a post code based retrieval system to locate cases geographically and link them to the underlying census enumeration districts, and hence to their populations at risk. Main outcome measures were comparison of observed/expected ratios (based on national rates) within bands delineated by concentric circles around point sources of environmental pollution located anywhere in Britain. MAIN RESULTS: The system is illustrated by a study of mortality from mesothelioma and asbestosis near the Plymouth naval dockyards during 1981-87. Within a 3 km radius of the docks the mortality rate for mesothelioma was higher than the national rate by a factor of 8.4, and that for asbestosis was higher by a factor of 13.6. CONCLUSIONS: SAHSU is a new national facility which is rapidly able to provide rates of mortality and cancer incidence for arbitrary circles drawn around any point in Britain. The example around Plymouth of mesothelioma and asbestosis demonstrates the ability of the system to detect an unusual excess of disease in a small locality, although in this case the findings are likely to be related to occupational rather than environmental exposure. PMID- 1431705 TI - Screening infants for hearing loss--an economic evaluation. AB - STUDY OBJECTIVE: The aim was to carry out an economic evaluation of the programme implemented in one district health authority for the screening of infants for hearing loss. DESIGN: The approach taken was a cost-effectiveness analysis using the methodology of decision analysis to model the options appraised: (1) the conventional screening policy was for a health visitor and colleague to screen at 8-9 months, and at 10 months for each child to be seen again by a clinical medical officer for a developmental assessment plus hearing screen if necessary; (2) the alternative policy was for screening to take place at 10 months only if concern is expressed (or if there is a clinical indication) at the developmental assessment; the introduction of a "clue list" was considered; (3) the third option was no screening. MAIN RESULTS: The annual expected cost per unit output was pounds 20.57 for the conventional screening policy, between pounds 11.13 and pounds 11.23 for the alternative policy, and pounds 11.27 for the third option of no screening. Introducing the "clue list" under the alternative screening policy is likely to raise the cost per unit output, but the effects are uncertain. CONCLUSIONS: The results suggest that the alternative screening policy is more cost-effective than the conventional policy, but has little advantage over not screening at all. The effects of introducing a clue list need further investigation. PMID- 1431706 TI - Factors influencing childhood immunisation in an urban area of Brazil. AB - STUDY OBJECTIVE: The aim was to examine the factors associated with incomplete vaccination in an urban area in Sao Paulo, Brazil; and to explore whether differences in vaccine coverage in the catchment area of health centres remain after the demographic constitution of the population in these areas is controlled for. DESIGN: The children were selected as controls for a case-control study. 455 children were selected at random (but age matched) from the health centre registries. Data was collected from the health centre records and from home interviews. SETTING: All children were registered in FAISA, a municipal health service comprising a large network of health centres and hospitals. FAISA's services are free at the point of delivery, and over 85% of the city's children are registered. PARTICIPANTS: Participants were selected to represent, except in their age distribution, all children registered in the municipal health service. MEASUREMENTS AND MAIN RESULTS: Information was collected on subjects' vaccine history, year of birth, sex, birth order and birth weight, and health centre of registration; their mothers' age, education, and marital status; and the family's income per capita and history of migration. Analysis was undertaken to identify risk factors for vaccination and whether the differential coverage in health centres' catchment areas remained after demographic characteristics of the population were controlled for. The high coverage for DPT and polio vaccines suggests that low overall coverage was not simply a result of mothers failing to bring children for vaccination. The variable that best predicted vaccine coverage was year of birth. Children born to immigrant mothers or into large families had lower vaccine uptake. The characteristics of children and their mothers did not account for the variation in vaccination coverage in catchment areas of different health centres. CONCLUSIONS: It is likely that in this area vaccination completeness was associated mainly with the health centre's ability to deliver vaccination to the target population. PMID- 1431707 TI - A case-control evaluation of the effect of breast cancer screening in the United Kingdom trial of early detection of breast cancer. AB - OBJECTIVE: The aim was to assess the extent to which selection bias affects a case-control study of breast cancer screening in which attenders and non attenders for screening are compared. DESIGN: There were two retrospective case control studies, one estimating the risk of death from breast cancer in women in the screening district relative to those in the comparison district (study A), the second estimating the relative risk for women who had ever been screened compared with women who had never been screened in the screening district alone (study B). For cases and controls in study B, the women's screening history was summarised for the time period from date of entry to diagnosis of the case, or the equivalent time from date of entry for the matched controls. For cases detected by screening, the screen at which cancer was detected was included in the screening history. SUBJECTS: Cases were deaths from breast cancer in women with disease diagnosed after entry to the trial, up to 31 December 1986 or a maximum of seven years from date of entry, in one of the screening districts (Guildford) and one of the comparison districts (Stoke) participating in the UK Trial of Early Detection of Breast Cancer: study A: 198 deaths in Guildford and Stoke; study B: 51 deaths in Guildford only. There were five age matched controls for each case, with length of follow up at least as great as the time from entry to death of the case. MAIN RESULTS: The estimate of the risk of death from breast cancer in the screening district relative to the comparison district from study A was 0.76, thus implying a reduction of 24% in the screening district, similar to that obtained from a cohort analysis of data from the two districts. In contrast, the relative risk in study B for ever v never screened women was 0.51, which, taking the 72% compliance into account, would result in a relative risk of 0.65 for the screening district if there were no selection bias. The risk of breast cancer mortality in the never screened relative to the comparison district was 1.13, despite the fact that incidence rates in the two populations were similar. This suggested that cancers in the never screened group had a particularly poor prognosis, contributing to selection bias. CONCLUSIONS: The possible existence of selection bias should lead to caution in interpretation of the results of case control studies of the effect of breast cancer screening on mortality. PMID- 1431708 TI - Influence of rural environment on diagnosis, treatment, and prognosis of colorectal cancer. AB - STUDY OBJECTIVE: Several studies have shown that residential location (urban or rural) influences the incidence of colorectal cancer. The aim was to investigate the influence of rural environment on colorectal cancer history and survival in a well defined population. DESIGN: Patients with colorectal cancer diagnosed in the department of Calvados (France) were classified by place of residence (urban/rural) and information on clinical symptoms, tumour extension, treatment, and survival was collected. SETTING: The study was population based, in the department of Calvados in France. PATIENTS: During 1978-1984, 1445 colorectal cancers were collected by the Digestive Tract Cancer Registry of Calvados, 1047 with an urban place of residence (544 males and 503 females) and 284 with a rural place of residence (134 males and 150 females). MEASUREMENTS AND MAIN RESULTS: In both sexes, rural patients with colorectal cancers were treated less frequently in a specialised health care centre (40.0%) than patients from an urban population (53.4%). The difference was mainly but not entirely explained by distance from the specialised health care centre. In females in the rural population, cancers were diagnosed more frequently at the stage of severe clinical symptoms (22.1%) and metastases (18.8%) than they were in the urban population (15.5% and 12.3%). In addition among females a rural environment appeared to confer a worse prognosis (relative risk = 1.3). CONCLUSIONS: Our findings suggest an inequality between rural and urban populations, especially for women. The loneliness of rural women leads to a delay in diagnosis and worse survival. In health education campaigns on colorectal cancer, efforts must be made to provide medical information to rural women in order to reduce the delay in diagnosis and improve survival. PMID- 1431709 TI - Coefficients of relationship by isonymy among registrations for five common cancers in Scottish males. AB - STUDY OBJECTIVE: The aim was to assess the relative importance of genetic factors in carcinoma of the stomach, colon, rectum, prostate, and bladder in Scottish males. DESIGN: Cancer cases and controls were compared in terms of the coefficient of relationship by isonymy (Ri). SETTING: Surname distributions for cancer cases were derived from the Scottish Cancer Register for the years 1959 85. Control distributions were derived from all births, marriages and deaths in Scotland for 1976. SUBJECTS: Analysis was carried out on a total of 60,933 cancer registrations and 101,836 births, marriages, and deaths over the 12 local government regions of Scotland. MAIN RESULTS: Comparisons of Ri within and between regions indicated that inherited susceptibility was of greatest importance in carcinoma of the prostate and colon, of intermediate importance in carcinoma of the rectum and stomach, and of minimal importance in carcinoma of the bladder. Familial aggregation of cancers was most pronounced in Highland, Tayside, and Borders Regions. For Highland, this appeared to be the result of region-specific familial influences, while Tayside and the Borders shared genetic factors contributing to cancer aetiology with neighbouring regions in south east Scotland. CONCLUSIONS: Surname analysis is a simple but useful tool for studying population genetic structure and its relationship to disease incidence. PMID- 1431710 TI - Projections of cervical cancer mortality and incidence in New Zealand: the possible impact of screening. AB - STUDY OBJECTIVE: The aim was to estimate the likely burden of cervical cancer in New Zealand over the next two decades, according to whether cervical screening services are made more effective. DESIGN: The study was based on national mortality and incidence data for the periods 1954-87 and 1954-86, respectively. An age-period-cohort model was used to estimate the contributions of age, time period, and birth cohort effects to the occurrence of cervical cancer. Using age specific estimates of the future female population of New Zealand, projections of cervical cancer mortality and incidence until the year 2008 were derived from the model. Projections were made assuming either that screening services will not be improved, or that an immediate improvement in the organisation of screening will lead to a decline in period effects for incidence of 15% per five year time period (with a slightly delayed effect on mortality). It was also assumed either that the risk in new birth cohorts will be similar to that in recent cohorts, or that their risk will be halved as a result of changes in sexual behaviour (due to education about AIDS or other factors). Combining these assumptions produced four sets of estimates, reflecting a range of possible scenarios. SETTING: Both the data used and the projections obtained related to the entire population of New Zealand women. MAIN RESULTS: For both mortality and incidence, projections were made of age specific rates, cumulative rates, and absolute numbers of deaths or new cases. With the first assumption about new birth cohorts, it was estimated that both mortality and incidence rates will increase if screening services are are not improved. In absolute terms, the present 100 deaths per year could increase to about 148 deaths per year, while there could be a much larger increase in incidence from 235 per year to about 440 per year). With improved screening, there could be a reduction in age specific mortality rates and a modest decline in the number of deaths, while a reduction in incidence rates would be accompanied by about the same number of new cases as at present. In comparison with improvements in screening, changes in the underlying risk in new birth cohorts would have much smaller effects on the occurrence of cervical cancer over the next two decades. CONCLUSIONS: Plausible improvements in cervical screening are likely to be accompanied by only small changes in the burden of cervical cancer over the next two decades. If screening services are not improved, however, there will be striking increases in both mortality and incidence. PMID- 1431712 TI - Further evidence of benefits of a (non-randomised) breast cancer screening programme: the DOM project. AB - STUDY OBJECTIVE: The aim was to demonstrate the benefits of breast cancer screening on mortality. DESIGN: The study was an evaluation of a breast cancer screening programme by means of different approaches: (1) a case-control study, breast cancer deaths being the cases; (2) comparing the numbers of breast cancer deaths in screened and unscreened women; (3) comparing breast cancer mortality before and after start of the programme; (4) comparing breast cancer mortality in different large cities; (5) comparing screening activity with mortality reduction. SETTING: The setting was a breast cancer screening programme in the city of Utrecht, the DOM project, for women aged 50-64 years old at intake, birth cohort 1911-1925. The programme started in 1974, and there were five screening rounds up to 1984. Participation rate in the first round was 72% (14,697 women). MAIN RESULTS: (1) Screening was protective against dying from breast cancer, odds ratio 0.52, with a stronger effect in older women and no evidence of confounding; (2) risk ratio of dying from breast cancer for women in the response group was the same as the odds ratio, 0.52; (3) breast cancer death rate after the start of the project was nearly 20% lower than before the project started; after correcting for women who could not have benefited from screening the reduction was 33%; (4) a rise in breast cancer mortality in birth cohort 1911-1925 seen in other large cities without a screening programme due to aging of the cohort was not seen in the city of Utrecht; (5) mortality reduction followed the screening activity with a time lag of approximately 5 years. CONCLUSIONS: Early diagnosis of breast cancer by mammography reduces breast cancer mortality in women 50-64 years old at intake; different approaches to the evaluation of the project give different estimates of the screening effect, making clear that the effect depends on the intensity of the programme. PMID- 1431711 TI - Social class, marital status, and cancer of the uterine cervix in England and Wales, 1950-1983. AB - STUDY OBJECTIVE: The aim was to investigate whether trends in mortality from cancer of the cervix uteri by age, marital status, and social class are compatible with current beliefs about the epidemiology of the disease. DESIGN: Data on mortality from cancer of the cervix for single and married women by age and social class were obtained from the Registrar General's Decennial Supplements on occupational mortality for the years 1950-53, 1959-63, 1970-72, and 1979, 1980, 1982, and 1983. Age standardised mortality rates were calculated directly by social class and marital status. SETTING: The data relate to all cases of carcinoma of the cervix reported in England and Wales in the years studied. MAIN RESULTS: There was a marked convergence of mortality between single and married women over the period within every social class grouping examined. The social class differential, however, remained essentially unchanged for both single and married women considered separately. CONCLUSIONS: Trends in mortality by marital status appear to reflect accurately the changes in the pattern of marriage and sexual behaviour that have taken place in the post-war period, whereas the patterns of other risk and protective factors such as screening explain these trends less well. In contrast, it seems likely that factors other than patterns of sexual behaviour and screening operate to maintain the social class differential in England and Wales. PMID- 1431713 TI - Contributions of incidence and case fatality to mortality from bladder cancer in the south Thames Regions. AB - STUDY OBJECTIVE: The aim was to assess the individual contributions of incidence and case fatality to variations in bladder cancer mortality between districts in the South Thames Regions. DESIGN: The standardised mortality ratios for bladder cancer were calculated for the health districts in the South Thames Regions using data from the Thames Cancer Registry. The results were compared with the standardised registration ratios, used as a measurement of incidence, and survival hazard function, used as a measurement of case fatality. As one determinant of case fatality is the severity at presentation, mortality was also compared with the standardised proportion of cases with advanced disease at diagnosis. SETTING: The study took place in the 28 health districts in South East and South West Thames regional health authorities. SUBJECTS: Subjects were 3271 cases of bladder cancer aged 15-74 years resident in one of the two South Thames regional health authorities at diagnosis and registered between 1982 and 1985. MAIN RESULTS: The standardised mortality ratios for the different districts varied from 62 to 139. The standardised registration ratios, the survival hazard functions adjusted for age and stage of disease at diagnosis, and the proportion of cases with severe disease at diagnosis were all independently and significantly related to the standardised mortality ratios in each district. CONCLUSIONS: Mortality from bladder cancer was significantly related to measurements of incidence, case fatality, and severity at presentation. These relations have implications for the health services. The incidence of disease may be modified through preventative measures, the case fatality through improved quality of care, and severity at presentation possibly through prompt management of patients with haematuria. Further studies are needed to investigate why these factors have high values in some districts. PMID- 1431714 TI - Racial differences in ill defined cancer mortality in the United States and in the District of Columbia. AB - STUDY OBJECTIVE: The aim was to examine the epidemiology of unknown primary cancer mortality in the USA during 1979 to 1988 by age, sex, race, year, and geographical area. DESIGN: National (US) and state data were abstracted for deaths due to ill defined cancer (ICD-9 195.0 to 199.1) and all cancers combined (ICD-9 140.0-209.9). Age adjusted mortality rates were calculated using the 1980 USA population as the standard, and standardised rate ratios were derived. National total cancer incidence data were obtained from the surveillance, epidemiology and end results (SEER) program, and age and sex specific relative (black/white) cancer incidence rates were derived and compared to relative (black/white) mortality rates for ill defined cancer. State and regional median family income levels were obtained from the 1980 census and compared to corresponding mortality rates. SETTING: This study used data for the US population, the 50 states, and the District of Columbia. MEASUREMENTS AND MAIN RESULTS: During 1984-1988, ill defined cancers accounted for an average of 34,921 deaths each year in the USA (13.7 per 100,000 population). The mortality rate due to ill defined cancers is greater among blacks (19.3 per 100,000) than whites (13.2 per 100,000) (RR = 1.5) and has not declined since 1979. There is considerable geographical variation in the ill defined cancer mortality rate. Thus among blacks the highest rates were clustered in the central states (23 per 100,000) and the lowest rates were seen in the mountain and western states (17 per 100,000). The District of Columbia had the highest overall rate (21.7 per 100,000) when compared to all other states. The black/white relative mortality rate due to ill defined cancer was consistently greater than the black/white relative incidence of all cancers. CONCLUSIONS: Ill defined cancer mortality is the fourth leading site of cancer mortality in the USA, and accounts for 7.4% of cancer deaths annually. The large proportion of ill defined cancer deaths may have biased the accuracy of national and local cancer incidence and mortality statistics. The higher mortality of ill defined cancer among blacks is not explained by the higher overall cancer incidence among blacks and suggests the influence of socioeconomic or cultural barriers that may result in underutilisation of health services or substandard health care. Ill defined cancer mortality may be a sentinel indicator of deficiencies in the health care delivery system as well as a measure of progress against cancer. PMID- 1431715 TI - Adding years to life: effect of avoidable mortality on life expectancy at birth. AB - STUDY OBJECTIVE: The aim was to determine the number of years that could be gained by preventing avoidable deaths. DESIGN: The study arose from the concept of avoidable causes of death and life expectancy at birth. Four abbreviated life tables were computed. The first included all causes of death; the second excluded all avoidable causes of death; the third and fourth excluded respectively primary and secondary avoidable causes of death. SETTING: Mortality and population data were taken from Mortality Statistics Offices in Valencia Region, Spain. MAIN RESULTS: Life expectancy at birth (LEB) was 75.7 years. After removing all avoidable deaths, LEB increased by 1.74 years. This improvement is attributed to avoidable deaths by primary prevention (1.09 years) and avoidable death by secondary prevention (0.37 year). CONCLUSIONS: According to these results the greatest improvement in LEB would be gained by primary prevention. PMID- 1431716 TI - Childhood blood pressure, body build, and birthweight: geographical associations with cardiovascular mortality. AB - STUDY OBJECTIVE: The aim was to examine whether blood pressure, body build, and birthweight differ between areas of England and Wales with widely differing adult cardiovascular mortality rates. DESIGN: This was a cross sectional survey of children in five towns with exceptionally high and five towns with exceptionally low current adult cardiovascular mortality. SETTING: The study was a school based survey. SUBJECTS: 3842 children aged 5.0-7.5 years were selected by stratified random sampling of primary schools (response rate 76%). MEASUREMENTS AND MAIN RESULTS: Blood pressure, pulse rate, height, and weight were measured and birthweight was assessed by maternal recall. Children in towns with high cardiovascular mortality rates were significantly shorter than those in towns with low cardiovascular mortality rates (mean difference 0.9 cm, 95% confidence interval 0.4 to 1.4 cm) and had slightly higher body mass indices (mean difference 0.12 kg/m2, 95% CI -0.03 to 0.27 kg/m2). Mean birthweights were slightly lower in high mortality towns (mean difference 34 g, 95% CI -10 to 78 g), while the proportion of children with low birthweight (< 2500 g) (8.1%) was significantly higher than that in low mortality towns (5.5%) (p = 0.005). Mean differences in blood pressure between high and low mortality towns were small and non-significant, even after adjustment for height. The differences in height between high and low mortality towns were largely independent of social class. However, differences in mean birthweight were markedly reduced once social class was taken into account. CONCLUSIONS: No geographical relationship between childhood blood pressure and adult cardiovascular mortality was detected. Although it is possible that the differences in mean height and body mass index between towns with differing adult cardiovascular mortality may have implications for future patterns of health in these towns, the absence of marked differences in birthweight and blood pressure suggests that hypotheses proposing a direct relationship between intrauterine experience and adult cardiovascular mortality will have limited relevance to geographical variation in cardiovascular disease in this generation. PMID- 1431717 TI - Level of education, lifestyle, and morbidity in two groups of white collar workers. AB - STUDY OBJECTIVE: The aim was to examine the relationship between level of education, lifestyle, and morbidity in two groups of male white collar workers, and to determine whether any differences found could be related to objective differences in working conditions. DESIGN: The study was a survey of a random sample of commercial travellers and a sample of men with sedentary occupations, representing two different groups of white collar workers. Survey interviews were conducted during the annual compulsory medical examination. Subjects were classified into three levels of education and differences according to level of education were studied in relation to 40 frequent health problems, lifestyle variables, body mass index, height, and working conditions. SUBJECTS: There were 1364 men in the commercial traveller group, mean age 39.5 years, and 525 men in the sedentary group, mean age 36.2 years. There were 22 exclusions because of unclassifiable levels of education and four refused to be interviewed. SETTING: The study took place in 11 towns in France. MAIN RESULTS: When age was taken into account there were only minor differences in the prevalence of health disorders. Lifestyle variables and height were clearly related to the level of education. Observed differences could not be explained by constraints or declared difficulties in working conditions. CONCLUSIONS: Differences in health practices related to level of education are observed even in groups that are relatively homogeneous socially. Lifestyle may be important as an intermediate determinant of health disorders among less educated people. PMID- 1431718 TI - Public health implications of dietary differences between social status and occupational category groups. AB - STUDY OBJECTIVE: As there is a social status gradient in chronic disease mortality in Australia, this study aimed to establish whether there were substantial differences among socioeconomically defined groups with respect to food choice and nutrient intake, in the context of risk of nutrition related chronic diseases. DESIGN AND PARTICIPANTS: Cross sectional data were collected from a randomly selected population sample of 1500 urban Australian adults. Data were collected by postal questionnaire, which included an assessment of dietary intake and questions on sociodemographic details. Three measures of social position were collected: occupation, educational status, and income status. Occupation was interpreted both on a continuous, prestige scale, and also as categorical occupational groupings. MAIN RESULTS: The study achieved a 70% response rate. Higher social status was generally associated with healthier dietary intakes, with lower fat and refined sugar densities, and higher fibre densities, but also with higher alcohol density. No differences were found in salt, polyunsaturated fat, protein, or complex carbohydrate densities across groups. Food intake differences were also found between occupational status groups, with the upper social groups tending to consume more wholegrain cereal foods, low fat milk, and fruit, and less refined cereal foods, full cream milk, fried meat, meat products, and discretionary sugar; but also more cheese and meat dishes. CONCLUSIONS: Although this study did show statistically significant differences across social status groups in relation to nutrient and food intakes, these differences were small compared to the disparity between intakes of all groups and the recommended patterns of intake, and did not appear to be great enough to be a major explanatory variable in differences in disease risk across groups. PMID- 1431719 TI - Clustering of dietary variables and other lifestyle factors (Dutch Nutritional Surveillance System). AB - STUDY OBJECTIVE: The aim was to investigate whether dietary factors cluster in a favourable or unfavourable way and to characterise the groups identified by lifestyle and sociodemographic variables. DESIGN AND SETTING: This cross sectional study was based on data of the 1987-1988 Dutch national food consumption survey (DNFCS), obtained from a panel by a stratified probability sample of the non-institutionalised Dutch population. PARTICIPANTS: 3781 adults (1802 males and 1979 females) of the DNFCS, aged 19 to 85 years, were studied. MEASUREMENTS AND MAIN RESULTS: To estimate dietary intake two day food records were used. Lifestyle factors were collected by structured questionnaire and sociodemographic variables were available from panel information. Cluster analysis was used to classify subjects into groups based on similarities in dietary variables. Subsequently, these groups were characterised by sociodemographic and lifestyle factors as well as by the consumption of food groups. Eight clusters were found. In comparison with the guidelines, the dietary quality in four clusters was poor. The cluster with the poorest dietary intake (high intake of fat, cholesterol, and alcohol; low intake of dietary fibre) showed on average a high consumption of animal products (except milk), fats and oils, snacks, and alcoholic beverages, and a low consumption of fruit, potatoes, vegetables, and sugar rich products. Smoking, body mass index, dietary regimen on own initiative, hours of sleep, gender, age, socioeconomic status, and day of the week were found to discriminate among the clusters. CONCLUSIONS: Cluster analysis resulted in substantial differences in mean nutrient intake and seems useful for dietary risk group identification. Undesirable lifestyle habits were interrelated in some clusters, but an exclusive lifestyle for health risk has not been found. PMID- 1431720 TI - Fair, and still a sun lover: risk of gallstone formation. AB - STUDY OBJECTIVE: The aim was to evaluate the hypothesis that sunlight exposure leads to the development of gallstones in people with a sun sensitive skin. DESIGN AND SETTING: This was a case-control study among 206 white patients referred for an ultrasound examination of the gallbladder. Sunlight exposure and skin sensitivity were retrospectively assessed by a structured questionnaire. The questionnaire was taken before the outcome of the ultrasound examination was known, so that the patients and the interviewers were blind to the outcome. The main outcome measure was gallstones in the gallbladder detected by ultrasound. MAIN RESULTS: 87 patients had gallstones (cases), 119 had none (controls). In subjects with a skin sensitive for sun (Fitzpatrick skin type I) a positive attitude to sunbathing was associated with a higher risk of gallstones than a negative attitude. In subjects with an insensitive skin (skin type IV) no association was found. CONCLUSIONS: This study confirms a hypothesis which was based upon metabolic research. However it is too early to upgrade the first "F" in the traditional adage that gallstone patients are "fair, fat, female, fertile and forty". Since both epidemiological and pathobiological evidence is scarce, the role of sun and/or (ultraviolet) light exposure and skin sensitivity in the aetiology of gallstones should be confirmed by further research. PMID- 1431721 TI - Channelling of controlled release formulation of ketoprofen (Oscorel) in patients with history of gastrointestinal problems. AB - STUDY OBJECTIVE: The aim was to determine if a new controlled release formulation (Oscorel) of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen has been preferentially prescribed in patients with prior history of gastro-intestinal disturbances. DESIGN: The study was a pharmacy records based comparison of the rates of prior prescribing of drugs indicated for peptic ulcer treatment in first recipients of Oscorel in 1989 versus recipients of other NSAID products. SETTING: A representative panel of Dutch community pharmacies serving approximately 425,000 people was used. MAIN RESULTS: Oscorel was launched in January 1989. Data on prescriptions dispensed in 1987-1988 to a total of 837 first users of Oscorel were analysed and compared with the dispensing history of a reference population including 30,787 patients who did not receive a prescription for Oscorel during 1989. Compared to the reference population, first users of Oscorel included a greater proportion of females, of patients 75 years and older, of heavy users of NSAIDs, and of patients switching among different NSAIDs. A total of 24.1% of first users of Oscorel had received peptic ulcer therapy in 1987-1988, versus 15.7% of the reference population. The rate ratio was 1.54, with 95% confidence interval of 1.36-1.74. Adjustment for stratifying variables caused only minor changes in the rate ratio, which remained stable on 1.5. CONCLUSIONS: Oscorel appears to have been channelled into use in patients with recognised risk factors for gastrointestinal toxicity. This preferential prescribing probably resulted from expectations and claims that this product has a lower risk of such toxicity. PMID- 1431722 TI - Changing incidence of peptic ulcer--facts or artefacts? A cohort study from Tromso. AB - STUDY OBJECTIVE: The aim was to estimate the age and sex specific incidences of duodenal and gastric ulcers censored for death and migration. DESIGN: A population based cohort was followed seven years through records of x ray examinations, endoscopies, and operations in the only hospital serving the area. SETTING: The study was conducted in the municipality of Tromso, Northern Norway, where all men aged 20 to 54 years and women aged 20 to 49 years in 1980, a total of 21,440, were included. MAIN RESULTS: We found an incidence of 1.47 (95% CI 1.21-1.76) and 0.88 (0.67-1.14) per 1000 person-years for gastric and 1.98 (1.69 2.31) and 0.85 (0.64-1.11) for duodenal ulcers in men and women, respectively. A small and insignificant sex difference for gastric ulcer was noted. The duodenal preponderance in men was only recognised among the ulcers identified by x ray, not among ulcers diagnosed by endoscopy. CONCLUSIONS: This population based study has, in contrast to recent studies from other areas, revealed an unchanged high incidence of gastric and duodenal ulcer in both sexes. Compared to earlier studies from this area it indicates a preponderance of duodenal ulcers. The study also shows the impact of attendance rate, death, and migration, and of diagnostic methods on the incidence estimates. Ignoring these potential biases may lead to conclusions on peptic ulcer trends that reflect artefacts rather than real changes in peptic ulcer occurrence. PMID- 1431723 TI - Pulmonary function development in children with past history of asthma. AB - STUDY OBJECTIVE: The aim was to examine whether or not the children with a past history of asthma but free from asthmatic attacks for several years show a different growth pattern in pulmonary function from control children. DESIGN: A community based cohort was surveyed three times during a four year follow up period. SETTING: Kashima district in Ibaraki prefecture, Japan. PARTICIPANTS: In 1980, 441 primary school children between 113 and 124 months of age were enrolled as an initial cohort; 325 of these provided reliable results in each of the three surveys. MAIN RESULTS: A level and a slope of FVC, FEV1, Vmax50, and Vmax25 were calculated for each child, based on a general linear model analysis. Past histories of each child were determined from a standardised questionnaire. The children with a history of doctor diagnosed asthma showed a lower Vmax50 level (p < 0.005) and a lower level and slope of Vmax25 (p < 0.005, p < 0.01) than control children, even when only those who did not suffer from wheezing attacks during the follow up period were considered. CONCLUSIONS: Indices of peripheral airways function in children with an asthmatic history were reduced even if they had been in remission for several years. The difference in pulmonary function in comparison to control children might become greater at the time of the adolescent growth spurt. PMID- 1431724 TI - Impact of headache on sickness absence and utilisation of medical services: a Danish population study. AB - STUDY OBJECTIVE: The aim was to study the extent and type of health service utilisation, medication habits, and sickness absence due to the primary headaches. DESIGN: This was a cross sectional epidemiological survey of headache disorders in a general population. Headache was diagnosed according to a structured interview and a neurological examination using the criteria of the International Headache Society. SETTING: A random sample of 25-64 year-old individuals was drawn from the Danish National Central Person Registry. All subjects were living in the Copenhagen County. PARTICIPANTS: 740 subjects participated (76% of the sample); 119 had migraine and 578 had tension type headache. MAIN RESULTS: Among subjects with migraine 56% had, at some time, consulted their general practitioner because of the migraine. The corresponding percentage among subjects with tension type headache was 16. One or more specialists had been consulted by 16% of migraine sufferers and by 4% of subjects with tension type headache. The consultation rates of chiropractors and physiotherapists were 5-8%. Hospital admissions and supplementary laboratory investigations due to headache were rare (< 3%). Half of the migraine sufferers and 83% of subjects with tension type headache in the previous year had managed with at least one type of drug in the current year. Acetylsalicylic acid preparations and paracetamol were the most commonly used analgesics. Prophylaxis of migraine was used by 7%. In the preceding year 43% of employed migraine sufferers and 12% of employed subjects with tension type headache had missed one or more days of work because of headache. Most common was 1-7 days off work. The total loss of workdays per year due to migraine in the general population was estimated at 270 days per 1000 persons. For tension type headache the corresponding figure was 820. Women were more likely to consult a practitioner than men, whereas no significant sex difference emerged as regards absenteeism from work. CONCLUSIONS: The impact of the headache disorders on work performance in the general population is substantial, and the disorders merit increased attention. PMID- 1431725 TI - The problem of diagnostic variability in general practice. AB - STUDY OBJECTIVE: The aim was to examine the scale, source, and relevance of variation between general practices in respect of the rates with which patients consulted with illnesses falling in each of several diagnostic groups. DESIGN: This study involved a general practice morbidity survey conducted over two years, 1970-72. All patients who consulted their general practitioners were identified and the number of these who consulted with diagnoses attributable to each of the 18 main chapters of the International classification of diseases were counted. Patients who consulted for more than one diagnosis within a chapter were counted once only; those who consulted for one or more diagnoses in each of several chapters were counted once for each chapter. SETTING: This was a national survey involving general practitioners in England and Wales. SUBJECTS: The study involved 214,524 patients from 53 selected general practices (115 doctors) who were registered with their general practitioners for the whole of the year 1970 71 and for whom their morbidity data had been linked with their social data from the 1971 census. MEASUREMENTS AND MAIN RESULTS: Using the numbers of patients on the practice lists as denominators, practice patient consulting rates (PPCR) were calculated for each practice and for each ICD chapter. Variability in chapter PPCR was examined by calculating coefficients of variation and, after allowance for random variation, coefficients of residual variation. There were large interpractice (doctor) variations in all chapter rates. These variations were only marginally attributable to: chance; different age, sex and social class mixes of practice populations; geographical locations; and practice organisation. The rates were, however, consistent from one year to the next for any one practice. Approximately half of the interpractice (doctor) diagnostic variability was associated with overall patient consulting behaviour. When the effects of this behaviour were discounted, any major residual diagnostic variability was confined largely to ICD chapters I-V, XVI, and XVII, ie, those chapters where aetiology forms the basis of classification. CONCLUSION: Variations in recorded diagnostic rates are mainly due to the consistent but idiosyncratic and selective exclusion by practitioners of some components from the total set which often coexist in a new diagnosis. Because of the scale of interpractice diagnostic variability, the use of algorithms and information technology is largely precluded from outcome studies, auditing procedures, and studies of practice work loads in general. However, (1) the consistency of any individual doctor's pattern of diagnostic recording from one year to another permits studies of trends; and (2) given a reasonable number of recording practices, the population mean practice consulting rates can be estimated with sufficient accuracy for many epidemiological research and administrative uses. PMID- 1431726 TI - Demographic characteristics and health behaviours of consenters to medical examination. Results from the Welsh Heart Health Survey. AB - STUDY OBJECTIVE: The aim was to compare the demographic characteristics and health related behaviours of people who consented to a medical examination as part of a population survey with those who did not. STUDY DESIGN: The study formed part of the (1985) Welsh Heart Health Survey, which comprised a three stage design involving household interview, self completion questionnaire, and medical examination. Subjects for medical examination were selected from responders to the questionnaire survey (67%). Sixty six per cent of this group consented to medical examination (n = 11,637). Odds ratio analysis techniques were used to compare consenters and non-consenters. MEASUREMENTS AND MAIN RESULTS: The analysis was based on self reported information available from previously completed questionnaires, and from personal interviews. The study supported the findings of previous research indicating that consenters to medical examination are more likely to be from non-manual social groups, to be aged 25-44 years, to be educated beyond school age, and to be married. Individuals with healthy lifestyle characteristics (diet, physical activity) were overrepresented among consenters. The only exception to this finding was in relation to excessive alcohol consumption. CONCLUSIONS: These findings emphasise the importance of maximising response rates in all forms of social research including surveys with a clinical component. They also have methodological and analytical implications for the Welsh Heart Health Survey. PMID- 1431727 TI - Effect of fathers' age and birth order on occurrence of congenital heart disease. PMID- 1431729 TI - The influence of temperature on power output of scup red muscle during cyclical length changes. AB - To gain insight into how temperature affects locomotory performance, we measured power output of scup red muscle during oscillatory length changes at 10 degrees C and 20 degrees C. When we optimized work loop parameters, we found that maximum power was 27.9 W kg-1 at 20 degrees C and 12.8 W kg-1 at 10 degrees C, giving a Q10 of 2.29. Maximum power was generated at a higher oscillation frequency at 20 degrees C (5 Hz) than at 10 degrees C (2.5 Hz), and the Q10 for power output at a given oscillation frequency ranged from about 1 at 1 Hz to about 5 at 7.5 Hz. An analysis of the results in terms of crossbridge kinetics suggests that the higher power output at 20 degrees C is associated with both a higher Vmax (i.e. more power per cycling crossbridge) and faster activation and relaxation (i.e. a greater number of cycling crossbridges). To obtain a more realistic understanding of the functional importance of temperature effects on muscle, we imposed on isolated muscle in vivo length changes and oscillation frequencies (measured during previous experiments on swimming scup) and the in vivo stimulus duty cycle (measured from electromyograms in this study). At 20 degrees C, muscle bundles tested under these in vivo conditions produced nearly maximal power, suggesting that the muscle works optimally during locomotion and, thus, important contractile parameters have been adjusted to produce maximum mechanical power at the oscillation frequencies and length changes needed during swimming. At 10 degrees C, muscle bundles tested under in vivo conditions produced much less power than was obtained during the 'optimized' work loop experiments discussed above. Furthermore, although 'optimized' work loop experiments showed that maximum power output occurs at 2.5 Hz, scup do not appear to swim with such a low tailbeat frequency. Although the reason for these apparent discrepancies at 10 degrees C are not known, it shows that simple extrapolation from isolated muscle to the whole animal, without knowledge of how the muscle is actually used in vivo, can be misleading. PMID- 1431728 TI - Calcium and potassium currents in leg motoneurons during postembryonic development in the hawkmoth Manduca sexta. AB - During insect metamorphosis the nervous system is reorganized to accommodate changes in behavior. In the hawkmoth, Manduca sexta, many identified larval motoneurons persist to innervate new adult muscles, while undergoing changes in dendritic morphology and synaptic connections. The thoracic leg motoneurons, for example, innervate different sets of muscles in the larva and adult and participate in distinct types of locomotor behavior in the two stages of life. To determine whether changes in the biophysical properties of these motoneurons accompany the structural and functional modifications that have been described, we used the whole-cell voltage-clamp technique to compare the Ca2+ and K+ currents expressed by leg motoneurons isolated from the larval, pupal and adult stages of Manduca. After 24 h in culture, the somata of leg motoneurons isolated from all three stages expressed voltage-sensitive Ca2+ currents that could be blocked by Cd2+, Co2+ or Ni2+. The currents were larger with Ba2+ as the charge carrier. The Ca2+ current density was significantly lower in these motoneurons during the early pupal stage than in either the larva or adult. Similar experiments revealed both transient and sustained K+ currents in the leg motoneurons that could be blocked with Cs+. There was a significant decrease in the density of the transient, inactivating outward current in leg motoneurons isolated from the early pupal stage. Thus, the levels of some types of ionic currents are modulated during metamorphosis. These changes may be important for the developmental or behavioral changes that accompany metamorphosis. PMID- 1431730 TI - Constrained and flexible features of rhythmical hindlimb movements in chicks: kinematic profiles of walking, swimming and airstepping. AB - Although studies of walking have generated many of the principles for motor control, walking is but one of the many behaviors that an animal produces. This study investigates the relationships among the kinematic profiles of three behaviors in chicks: walking, swimming and airstepping. In addition to describing features of the hindlimb movements, such as retraction and protraction, we also examined the intra- and interjoint coordination patterns at the hip, knee and ankle. By using multiple levels of analysis, we identified some features that are common to all three behaviors, and therefore appear to be constrained, as well as some dissimilar or flexible features. Specifically, we show that resistance differentially affects the hip, knee and ankle joints. Our results also show that each joint plays a distinctive role in these behaviors. For example, we suggest that the hip stabilizes the hindlimb and regulates the rhythmicity of its movements. We also show that movement at the knee consistently precedes movement at the other joints in each behavior. Finally, differences in ankle movements are the key features that discriminate one behavior from another. Continuity among prenatal, perinatal and postnatal behaviors in chicks is discussed. PMID- 1431731 TI - Evidence that fin whales respond to the geomagnetic field during migration. AB - We challenge the hypothesis that fin whales use a magnetic sense to guide migration by testing for associations between geophysical parameters and the positions where fin whales were observed over the continental shelf off the northeastern United States. Monte Carlo simulations estimated the probability that the distribution of fin whale sighting was random with respect to bottom depth, bottom slope and the intensity and gradient of the geomagnetic field. The simulations demonstrated no overall association of sighting positions with any of these four geophysical parameters. Analysis of the data by season, however, demonstrated statistically reliable associations of sighting positions with areas of low geomagnetic intensity and gradient in winter and fall, respectively, but no association of sighting positions with bathymetric parameters in any season. An attempt to focus on migrating animals by excluding those observed feeding confirmed the associations of sighting positions with low geomagnetic intensity and gradient in winter and fall, respectively, and revealed additional associations with low geomagnetic gradients in winter and spring. These results are consistent with the hypothesis that fin whales, and perhaps other mysticete species, possess a magnetic sense that they use to guide migration. PMID- 1431732 TI - The dissociation of repetition priming and recognition memory in language/learning-disabled children. AB - Recent research has found that the performance of learning-disabled and non disabled children is dissociated on explicit and implicit tests of memory (Lorsbach & Worman, 1989). The current study further examined this phenomenon by comparing language/learning-disabled (L/LD) and nondisabled children (NLD) on tasks measuring primed picture-naming and item recognition. Included within the design of the experiment was the manipulation of both presentation format (pictures or words) and retention interval (immediate or 1 day). Children were initially presented with pictures and words. Performance was measured both immediately and following a 1-day retention interval on a picture naming task, an item recognition task, and a supplementary measure of memory for presentation format. The magnitude of facilitation associated with primed picture-naming was found to be independent of item recognition performance. In addition, the effects of population (L/LD and NLD) and retention interval (immediate test or 1 day) each produced dissociations between the magnitude of naming facilitation and item recognition performance. Results were discussed in terms of their implications for our understanding of the nature of memory difficulties in L/LD children. PMID- 1431733 TI - Whole words and decoding for short-term learning: comparisons on a "talking computer" system. AB - Low-and average-ability readers in first and second grade studied a list of 36 words using a "talking-computer" system. The system highlighted and simultaneously pronounced orthographic units in the words when the children touched the words with a light pen. During two training sessions, the computer presented four groups of 9 words each, one group as whole words, one in syllabic units, one in subsyllabic units, and one as single grapheme-phoneme units. All children learned the least words with single grapheme-phoneme units, having had the greatest difficulty blending the units into words during training. The other presentation units did not differ significantly from each other for most students on post-testing. However, the low first-grade readers learned fewer words segmented and presented by subsyllables than by syllable or word units, but only for multisyllabic words. Monosyllabic words were blended and learned as easily with onset-rime segmentation as with whole word units, for all children. PMID- 1431734 TI - Perception of multidimensional stimuli: a differential-sensitivity account of cognitive processing and development. AB - A differential-sensitivity account of cognitive processing is described that emphasizes the development of perceptual sensitivity to object relations that are directly perceived. Four experiments are presented that investigate this account and compare it to the integrality-separability view of development and the view that younger children are nonselective in their processing of multidimensional stimuli. Results show that stimulus differences are more salient than identities (Expt. 1), younger as well as older children are highly selective in their perception and classify stimuli by separate dimensions (Expt. 2), differential sensitivity affects the perceived magnitude of stimulus differences (Expt. 3), and younger and older children perceive separate dimensions in speeded classifications (Expt. 4). The importance of considering individual patterns of responses in cognitive and developmental research is also demonstrated. PMID- 1431735 TI - Studies in space orientation. II. Perception of the upright with displaced visual fields and with body tilted. AB - To overcome certain disadvantages of the tilted-mirror situation as a technique for separating visual and postural determinants of the perceived upright, a new procedure was developed. The S was presented with a small tilted room, on the back wall of which was a rod which he had to adjust to the true upright. In a first test, judgments of the rod were obtained with body upright, and under three different conditions of the field: (a) The S, standing at a distance from the tilted scene, viewed it through a tube which restricted his view to the interior of the scene. (b) The S stood directly in front of the scene without a tube. (c) The S stood at a distance from the scene, without a tube, so that he saw not only the tilted scene but the outer upright room as well. Under all three conditions the perceived vertical and horizontal were displaced significantly in the direction of the axes of the tilted scene. When an outer upright field was present, as in the third condition, the effect of the tilted scene upon the perceived upright diminished. In another experiment, judgments of the rod were obtained with body tilted, both to the same side as the field and to the opposite side. It was found that tilting the body resulted in an increased tendency to accept the tilted field as a basis for judging the upright. Not only were the perceived vertical and horizontal displaced further in the direction of the tilted scene, but a number of Ss perceived the tilted scene as fully upright. In another experiment there was found a tendency for the tilted scene to right itself with prolonged observation. In some cases the righting was complete, so that at the end of the observation period, the tilted scene was perceived to be fully upright. Under all conditions, striking individual differences were found in the extent to which the perceived upright was affected by the surrounding tilted field. There is evidence of considerably consistency in a person's performance under the different conditions employed. PMID- 1431736 TI - Tolman's cognitive analyses: predecessors of current approaches in psychology. AB - Hindsight is always helpful. I hope that I have provided some appreciation of why the experiment by Tolman et al. (1946) is a classic and deserves to be included in this series. Evaluating the extent to which this particular experiment actually influenced the development of all of the endeavors described above is difficult, and I leave it to those individuals who have an interest in the history of science to draw the appropriate conclusions. Even without direct causality, the continued relevance of this experiment is striking. We might all wish that we have sufficient foresight to investigate significant problems in such a way that our own contributions are still considered important almost 50 years after we make them. PMID- 1431737 TI - Studies in spatial learning. I. Orientation and the short-cut. 1946. AB - 1. The original rough formulation of the expectancy theory is difficult to distinguish from the alternative stimulus-response doctrines. Part of this difficulty results from the fact that implicit in this rough formulation, is a definition of the matrix "x expects a goal at location L," which makes it equivalent to the matrix "x runs down the practiced path," when certain conditions are fulfilled. Because of this difficulty, we have rejected this definition. 2. We have suggested instead a definition of the matrix "x expects a goal at location L" which makes it equivalent to the matrix "x runs down the path which points directly to the location L," when certain conditions are fulfilled. 3. To determine whether rats will run down such a path, whenever the original path is blocked, we have run 56 female rats in a situation which conformed to these conditions. 4. Thirty-six percent of the rats chose the path which pointed directly towards the location of the goal. The remaining rats were distributed over the other paths in a chance fashion. 5. We have concluded (1) that rats do learn to expect goals in specific locations, (2) that there are important similarities between this behavior and human symbolic behavior, and (3) that these similarities justify our using the word 'expectation' as a name for the disposition to short-cut when the original patch is blocked. PMID- 1431738 TI - Textons, visual pop-out effects, and object recognition in infancy. AB - Five experiments were conducted to determine whether primitive perceptual features, or textons, which Julesz (1984) identified in studies of texture segregation with adults, also affect object recognition early in development. Three-month-old infants discriminated Ts and Ls composed of overlapping line segments from +s but not from each other in a delayed-recognition test after 24 hr; however, Ts and Ls were discriminated from each other after only 1 hr. In a priming paradigm, Ts, Ls, and +s were discriminated from one another after 2 weeks. In succeeding experiments, infants exhibited adultlike visual pop-out effects in both delayed recognition and priming paradigms, detecting an L in the midst of 6 +s and vice versa; these effects were symmetrical. The pop-out effects apparently resulted from parallel search: Infants failed to detect 3 Ls among 4 +s. Clearly, some of the same primitive units that have been identified as the building blocks of adult visual perception underlie object recognition early in infancy. PMID- 1431739 TI - Structure and process in semantic memory: evidence from event-related brain potentials and reaction times. AB - Through scalp measurements of the electrical activity of the brain (event-related potentials, or ERPs) recorded while subjects verified the truth of sentences relating exemplars and categories (e.g., ALL DOGS ARE ANIMALS), inferences were made about aspects of semantic processing that were not directly reflected by overt responses. In particular, it is suggested that a negative ERP component that peaks about 400 ms after the onset of the sentence predicate (i.e., N400) is sensitive to structural aspects of semantic memory. The amplitude of this component was modulated by the relatedness of the subject and predicate terms, as well as the hierarchical level of both these terms, but was not sensitive to the truth value of a sentence. PMID- 1431740 TI - Optimizing the use of information: strategic control of activation of responses. AB - Recent studies indicate that subjects may respond to visual information during either an early parallel phase or a later focused phase and that the selection of the relevant phase is data driven. Using the noise-compatibility paradigm, we tested the hypothesis that this selection may also be strategic and context driven. At least part of the interference effect observed in this paradigm is due to response activation during the parallel-processing phase. We manipulated subjects' expectancies for compatible and incompatible noise in 4 experiments and effectively modulated the interference effect. The results suggest that expectancies about the relative utility of the information extracted during the parallel and focused phases determine which phase is used to activate responses. PMID- 1431741 TI - The role of spatial attention in visual word processing. AB - Subjects made lexical decisions on a target letter string presented above or below fixation. In Experiments 1 and 2, target location was cued 100 ms in advance of target onset. Responses were faster on validly than on invalidly cued trials. In Experiment 3, the target was sometimes accompanied by irrelevant stimuli on the other side of fixation; in such cases, responses were slowed (a spatial filtering effect). Both cuing and filtering effects on response time were additive with effects of word frequency and lexical status (words vs. nonwords). These findings are difficult to reconcile with claims that spatial attention is less involved in processing familiar words than in unfamiliar words and nonwords. The results can be reconciled with a late-selection locus of spatial attention only with difficulty, but are easily explained by early-selection models. PMID- 1431742 TI - Involuntary covert orienting is contingent on attentional control settings. AB - Four experiments tested a new hypothesis that involuntary attention shifts are contingent on the relationship between the properties of the eliciting event and the properties required for task performance. In a variant of the spatial cuing paradigm, the relation between cue property and the property useful in locating the target was systematically manipulated. In Experiment 1, invalid abrupt-onset precues produced costs for targets characterized by an abrupt onset but not for targets characterized by a discontinuity in color. In Experiment 2, invalid color precues produced greater costs for color targets than for abrupt-onset targets. Experiment 3 provided converging evidence for this pattern. Experiment 4 investigated the boundary conditions and time course for attention shifts elicited by color discontinuities. The results of these experiments suggest that attention capture is contingent on attentional control settings induced by task demands. PMID- 1431743 TI - Asymmetry in visual search for targets defined by differences in movement speed. AB - Perception of motion speed was investigated with the visual search paradigm, using human Ss. When searching for a fast target among slow distractors, reaction time was minimally affected as the number of distractors was increased. In contrast, reaction time to detect a slow target among fast distractors was slow and linearly related to the number of distractors. The effect cannot be attributed to differences in temporal frequency, discriminability, or one type of representation that might result from spatiotemporal filtering. An alternative hypothesis that can account for the asymmetry is that speed detectors operate as high-pass filters in the velocity domain. This hypothesis is in agreement with results obtained in psychophysical studies on motion adaptation as well as data from single-cell recordings in nonhuman species. PMID- 1431744 TI - Making two responses to a single object: implications for the central attentional bottleneck. AB - Experiments with two stimuli and two responses have revealed a central attentional bottleneck and pointed to response selection as its primary locus; however, little has been said about the underlying reasons for this bottleneck. Here we explore these reasons. In the first three experiments, Ss made two separate responses to different aspects of the same object. Interference between selection of the responses persisted, ruling out the possibility that the dual task bottleneck is caused by the input to the response-selection mechanism being limited to one object at a time. The next four experiments examined what happens when two responses are made to the same attribute of a single object. These experiments show that only one response selection occurred. Hence, the central mechanism is not limited to picking one motor action at a time. Several possible theories about the nature of the bottleneck are discussed. PMID- 1431745 TI - Intertrial interval and sequential effects in magnitude scaling. AB - The intertrial interval (ITI) was varied within subjects in magnitude estimation and cross-modality matching experiments. Fits of a recently proposed time series regression model show that the influence of the previous stimulus intensity on the current response decreases when the ITI is increased. The results can be interpreted as showing that an assimilative or additive perceptual or memory effect decreases with an increase in ITI. Fits of an earlier model, on the other hand, suggest that the influence of the previous stimulus intensity increases with an increase in ITI, which is counter to expectations. The new regression model (a) provides a simple explanation for the counterintuitive results obtained with the earlier model, (b) shows that assimilation in perception or memory can appear as contrast, and (c) reduces to a simpler model for longer ITIs. PMID- 1431746 TI - Inverse duration effects in partial report. AB - In partial-report experiments, an array of stimuli is displayed briefly, followed by a probe indicating the items to be reported. When exposure duration of the array is increased, 2 contrasting outcomes have been found: Some experiments find that performance improves (direct-duration effect); others find that it deteriorates (inverse-duration effect). The objective here was to identify the reasons for the discrepant results. This was done by investigating the roles played by 5 factors that differed between the 2 sets of contrasting studies. An inverse-duration effect was obtained in each of 6 experiments; its magnitude was affected by retinal eccentricity and by the number of items denoted by the probe. The effect was independent of array configuration and of number of items in the array. The direct-duration effect was shown to arise from a confounding of exposure duration and brightness. PMID- 1431747 TI - A psychophysiological study of the use of partial information in stimulus response translation. AB - Ss performed a hybrid go/no-go reaction task in which colored letters were assigned in various ways to 4 finger responses, 2 on each hand. In addition to reaction time, psychophysiological measures were used to assess the duration of stimulus identification and the onset of central and peripheral motor activity. The results suggest that response selection can begin on the basis of 1 stimulus dimension (e.g., color), while the other dimension (e.g., letter form) has not yet been identified. Other results are discussed with regard to "selection for action" (Allport, 1987) and the importance of stimulus-response translation strategies in the use of partial information. PMID- 1431749 TI - Position-linked interference in forming simple visual groups. AB - Experiments with 2-element visual groups reveal a form of interference that has several interesting properties. Observers judged the orientation of an imaginary line formed by 2 pixels (the target) while attempting to ignore a third pixel (the noise). Noise interfered with performance, even when it was made distinct from the target in various ways. This interference was strongly position linked; a single equation described the interference pattern for many different target noise configurations. Maximum interference was observed not when the noise was closest to the target but when it was at a distance of half the separation between target pixels. Some initial findings were consistent with the idea that visual grouping reflects the operation of visual channels with Gabor-like receptive-field profiles. But subsequent results implicated processes that automatically construct visual boundaries. PMID- 1431748 TI - Effects of preliminary perceptual output on neuronal activity of the primary motor cortex. AB - Observations of single neurons in the primary motor cortex of 1 monkey provided evidence that preliminary perceptual information reaches the motor system before perceptual analysis is complete. Neurons were recorded during a task in which 1 stimulus was assigned to a wrist flexion response and another was assigned to wrist extension. Two stimuli were assigned to a no-go response; each was visually similar to either the flexion or the extension stimulus. When a no-go stimulus was presented, neurons responded with weaker versions of the discharge patterns exhibited to the visually similar stimulus requiring a movement, suggesting that neurons receive partial perceptual information favoring that movement. Functionally separable neuronal populations were identified, and differences in the activations of these provide evidence about the functional effects of preliminary perceptual output on movement control processes. PMID- 1431750 TI - Do recognizable figures enjoy an advantage in binocular rivalry? AB - Five experiments examined whether recognizable stimuli predominate in binocular rivalry. It was found that a face predominated more than did a pattern equated for spatial frequency, luminance, and contrast; an objective reaction time procedure confirmed predominance of the face. The face was still liable to fragmentation as stimulus size increased. Observers tracked exclusive dominance of a picture of a camouflaged figure (a Dalmatian dog) prior to and then following discovery of the figure's presence; control observers received the same protocol with a scrambled version of the dog stimulus. Compared with control results, predominance of the dog picture was higher even before observers knew of the camouflaged figure. Inversion of the dog figure reduced its predominance. Binocular rivalry is sensitive to object-related, configural properties of a stimulus. PMID- 1431751 TI - Testing a semistochastic variant of the interactive activation model in different word recognition experiments. AB - A semistochastic variant of the interactive activation (IA) model of context effects in letter perception (McClelland & Rumelhart, 1981) was used to simulate response time distributions and means in different experiments investigating the effects of word frequency, neighborhood size and frequency, and orthographic priming in visual word recognition. The results provide evidence in favor of the connectivity assumption underlying the model but question the necessity of the interactivity assumption for simulating latencies in word recognition tasks. Together with those of a recent study by McClelland (1991), the present results suggest that 10 years after its appearance, the IA model's potential for testing hypotheses about the structure and dynamics of basic phenomena of human information processing in a variety of perceptual and cognitive tasks is not yet fully exploited. PMID- 1431752 TI - How do somersaulters land on their feet? AB - Body movements of trampolinists landing upright from forward somersaults, with eyes open and closed, were analyzed to test a theory of how braking and timing of actions are conjointly controlled. In regulating landing, rotation has to be slowed by extending the body so that it reaches the upright just as the feet hit the trampoline. Extending a theory of visual control of linear braking, it was hypothesized that upright landing is achieved by perceptually regulating body extension so as to keep the ratio angle of body to upright: rate of change of angle (the tau function of the angle) proportional to time-to-landing. The data support the hypothesis, indicate that vision improves precision of control, and argue further for the value of the tau function in the perceptual regulation of action. PMID- 1431753 TI - Selective reaching: evidence for action-centered attention. AB - Most studies of selective attention briefly present static 2-dimensional stimuli and require arbitrary responses such as verbal naming or a keypress. Many of our perceptual-motor interactions with the environment, however, require reaching directly toward an object while ignoring other objects in the scene. A series of experiments examines selective attention in the latter reaching situation. Effects previously observed in the traditional experimental procedures were obtained, suggesting that the models developed (which propose inhibitory mechanisms, e.g.) apply to ecologically valid situations. Attention accesses action-centered internal representations during such tasks. PMID- 1431754 TI - Visual space perception and visually directed action. AB - The results of two types of experiments are reported. In 1 type, Ss matched depth intervals on the ground plane that appeared equal to frontal intervals at the same distance. The depth intervals had to be made considerably larger than the frontal intervals to appear equal in length, with this physical inequality of equal-appearing intervals increasing with egocentric distance of the intervals (4 m-12 m). In the other type of experiment, Ss viewed targets lying on the ground plane and then, with eyes closed, attempted either to walk directly to their locations or to point continuously toward them while walking along paths that passed off to the side. Performance was quite accurate in both motoric tasks, indicating that the distortion in the mapping from physical to visual space evident in the visual matching task does not manifest itself in the visually open loop motoric tasks. PMID- 1431755 TI - Adaptive modification of saccadic eye movements. AB - Experiments are reported in which the target for a saccadic eye movement was displaced during the saccade. Subjects adapted to the displacement by altering the amplitudes of subsequent saccades to compensate for it. Analysis of kinematic details of the saccade trajectories revealed that the adaptation did not arise from a simple remapping of perceived target locations. Instead, the adaptation appeared to be accomplished by a change in the gain of the saccadic system. The gain change arose primarily from a change in the magnitude of the force pulse for the saccade, not a change in the duration of the pulse. These results have implications for the mechanisms that underlie saccades in normal situations. In particular, people can separately adjust the magnitudes and durations of the force pulses used to produce saccades. PMID- 1431756 TI - Temporal patterning in cascade juggling. AB - A key variable in cascade juggling is the proportion of time that a juggler holds onto a juggled object during a hand cycle, that is, the time from catch to throw in relation to the time from catch to catch. Space-time constraints and principles of frequency locking suggest 3/4 as the primary ratio and 2/3 and 5/8 as the most accessible options. In 5 experiments, object number, mass, and type (ball or scarf) were manipulated together with the frequency at which the objects were juggled. With 5 or 7 balls, the ratio was 3/4, independent of frequency. With 3 balls, the ratio decreased with frequency, with 3/4, 2/3, and 5/8 tending to predominate independently of the force variations induced by variation in object mass. With 3 scarves, ratios varied inversely with frequency and often exceeded 3/4. Implications for a dynamical theory of juggling were discussed with the issue of relative timing in coordination and the manipulation of task constraints as an experimental strategy. PMID- 1431757 TI - Rubbing your stomach while tapping your fingers: interference between motor planning and semantic judgments. AB - Previous research (Klatzky et al., 1989) shows that the time required to make sensible/nonsensible judgments about an action-object phrase (e.g., "rub your stomach") is reliably faster when the phrase is preceded by a cure representing a specific prototypical hand shape (vs. a neutral cue). The current experiments investigated the effects of preparing for an alternate task (finger tapping vs. syllable vocalization) on facilitatory priming of sensibility judgments. Preparation for finger tapping reduced the magnitude of the priming effect more than preparation for vocalization, suggesting that resources accessed during semantic processing of action-object phrases are also used during manual response preparation. The results support the existence of a system representing manual actions that is limited in the number of activities that can be represented at one time and that is not so general that it represents manual and vocal tract movements. PMID- 1431758 TI - Semantic congruity effects and theories of the comparison process. AB - Two experiments requiring comparisons of point locations on the line demonstrate that the magnitude of the response-time-based congruity effect parallels the form of the macro and the micro speed-accuracy trade-off function. This is predicted from the evidence accrual class of theories but is contrary to either the propositionally based semantic coding theory or the expectancy view. Very large accuracy-based congruity effects with comparisons of point locations in the plane are evident. Congruity effects arise because the duration of each evidence accrual is increased and the quality of the information is reduced as the distance of the stimulus representations from the instruction-activated reference point increases. This evidence accrual view is extended to account for the properties of perceptual and symbolic comparisons. PMID- 1431759 TI - Smoking cessation. PMID- 1431760 TI - Smoking cessation. PMID- 1431761 TI - Electrocardiogram interpretation. PMID- 1431762 TI - Giardiasis. PMID- 1431763 TI - Caring for victims of childhood sexual abuse. PMID- 1431764 TI - Family physicians and chiropractors: what's best for the patient? PMID- 1431765 TI - Low back pain: more than anatomy. PMID- 1431766 TI - Prevalence of lifetime sexual victimization among female patients. AB - BACKGROUND: State and federal statistics describe a lower incidence of rape and child abuse than is suggested by community prevalence rates. Victims of sexual assault may experience numerous short-term and long-term effects on psychosocial and physical health. They tend to use medical services more than nonvictims and are also more likely to seek medical care than mental health services. This study seeks to determine the prevalence of sexual victimization in a family practice setting. METHODS: Women 18 years of age or older presenting to a combined family practice and university student health center for a routine Papanicolaou smear or a health maintenance visit voluntarily completed an anonymous sexual experiences questionnaire of 28 close-ended items. RESULTS: Of 416 consecutive women, 405 agreed to participate. Of 147 family practice patients, 47.6% reported some type of contact sexual victimization during their lifetimes; 25.2% reported rape or attempted rape. Of 258 student health service patients, 57% had experienced contact sexual victimization, and 28.7% reported rape or attempted rape. Of those who reported unwanted sexual contact, 30% of the family practice patients felt they would not be comfortable discussing the experience with medical personnel, and 44.9% of the student health service patients would not feel comfortable doing so. CONCLUSIONS: Women with a history of unwanted sexual contact may be common in family practice and student health settings. Although treatment can be beneficial, many of these patients are not comfortable discussing their experiences with medical personnel. These findings suggest that there is potential benefit in obtaining a sexual victimization history as part of routine care, but further research will be necessary to assess the clinical benefit of such an approach. PMID- 1431767 TI - A comparison of the gastrointestinal side effects of two forms of erythromycin. AB - BACKGROUND: The gastrointestinal (GI) side effects of erythromycin frequently limit therapy and compliance. PCE Dispertab, a more expensive brand of erythromycin, has been promoted as a well-tolerated new dosage form; however, no studies compare its GI side effects with those of other forms of erythromycin. We compared erythromycin PCE (particles-in-tablet) with E.E.S. (erythromycin ethylsuccinate) to determine whether there is a difference in the incidence and severity of GI side effects. METHODS: This was a multicenter, prospective, single blind, randomized trial. Observers, but not participants, were blinded to the brand of erythromycin taken until after data analysis. We enrolled ambulatory patients who were at least 18 years old and weighed at least 90 lb for whom erythromycin had been prescribed at a dosage of 1.0 g/d. Subjects were given either the particles-in-tablet form, 333 mg three times daily, or the ethylsuccinate form, 400 mg four times daily, for 10 days and asked to report efficacy, compliance, and the frequency and severity of four GI symptoms (abdominal pain, nausea, vomiting, and diarrhea) in a daily diary. RESULTS: There were no significant differences between the particles-in-tablet and ethylsuccinate forms in incidence of GI side effects (63% and 61%, respectively), average daily GI symptom severity score (0.62 and 0.68, respectively), and GI related discontinuations (8.5% and 8.2%, respectively). The incidence of moderate or severe nausea was 5% for the particles-in-tablet form and 25% for the ethylsuccinate form (P < .001). CONCLUSIONS: Although ethylsuccinate caused a higher incidence of moderate to severe nausea, there were no differences in the three main outcome measures: incidence of GI side effects, average daily GI symptom severity score, and GI-related discontinuations. Therefore, we support prescribing erythromycin ethylsuccinate as a first line of treatment because it costs less. PMID- 1431769 TI - Body mass and weight as indicators for cholesterol screening. AB - BACKGROUND: Universal screening of serum cholesterol levels in adults has been recommended but not achieved. We were interested in factors that affected screening rates, and whether obese patients were more likely to have elevated cholesterol levels than other patients in our practice. METHODS: A sequential sample of charts was reviewed for height, weight, race, sex, diagnosis of hypertension or diabetes, and evidence of cholesterol screening. RESULTS: Of 604 adult patients, 32% had serum cholesterol measurements. No correlation was found between weight or body mass index and cholesterol levels. Patients with hypertension or diabetes were more frequently screened. Sex and race did not influence screening rates. CONCLUSIONS: In this population neither weight nor body mass index was associated with elevated serum cholesterol levels, suggesting that screening must be offered without regard to level of obesity in order to find those patients who will benefit from intervention. PMID- 1431768 TI - The many-voiced cultural story line of a case of diabetes mellitus. AB - An ethnographic approach is used to conduct and describe my research into a case of chronic illness and to assist the family physician's interventions. What at first appeared to be a frustrating, difficult-to-control case of diabetes mellitus was later revealed to be an intricate drama involving multiple voices and issues: marital, life stage, family, religious, occupational, regional, economic, and physician family-of-origin. Questions such as who has the disease?, what is the disease?, what keeps the disease going?, who is the patient?, and who is the clinician? are explored in the context of this case. The case was "solved" when the loss and sadness of aging was discovered and accepted during a cathartic session involving the diabetic patient, her husband, their family physician, and myself, a consultant. PMID- 1431770 TI - Contractual arrangements between residency programs and HMOs. AB - BACKGROUND: Although one out of seven health maintenance organizations (HMOs) is directly involved in graduate medical education (GME), either as an accredited sponsoring organization or through a contractual agreement with an academic medical center or teaching hospital to serve as an ambulatory rotation site, relatively little is known about the extent to which HMOs have provider contracts with faculty or residents of GME programs. Such provider contracts are not agreements to collaborate on the education of residents, but rather contractual arrangements under which individual physicians or groups (who happen to be residents or faculty) agree to provide services to HMO enrollees in return for some form of compensation. METHODS: In 1990, the Group Health Association of America conducted a survey of a sample of residency training programs in family medicine, internal medicine, and pediatrics to ascertain the extent to which (1) residents and faculty of residency training programs are participating physicians in HMOs; and (2) HMO enrollees are serving as the patient base for GME in ambulatory settings. RESULTS: Overall, 42% of the residency program respondents indicated that they contract with HMOs to provide services to enrollees. Nearly two thirds (64%) of family practice programs have provider contracts as compared with 28% of pediatrics programs and 24% of internal medicine programs. Provider contracts with independent practice associations are by far the most common, followed by group, network, and staff model contracts, in that order. CONCLUSIONS: It is apparent that provider contractual arrangements between HMOs and primary care residency programs are quite common, especially in the area of family practice. These contractual arrangements have probably resulted in a more predictable and stable patient revenue base for residency programs. The long-term effects on provider practice styles and the financing of graduate medical education are less clear. PMID- 1431771 TI - Family physicians, chiropractors, and back pain. AB - In this article, major aspects of back care provided to patients by family physicians and chiropractors are reviewed, and the recent guidelines on spinal manipulation therapy are discussed. These guidelines should be useful for family physicians wishing to refer patients to chiropractors. PMID- 1431772 TI - The computer-based medical record: current status. AB - At the turn of the century, neither hospitals nor physicians routinely kept clinical records. Since then, the medical record has gradually evolved. More recently, as society and medicine have become more complex and sophisticated, inadequacies of the paper medical record have become increasingly apparent. The computer-based medical record addresses many of the deficiencies of the paper record. Meanwhile, barriers to computer-based records have decreased; hardware has become more affordable, powerful, and compact, and software has been refined. Socially, the major payers for health care are demanding verification of the effectiveness and quality of care, information that involves data-intensive research. The electronic medical record promises to improve quality of care by providing point-of-care reminder and decision support tools as well as a database for substantiating the effectiveness of care. In conjunction with the growing integration of computers into all facets of life, government agencies, computer giants, and medical organizations are currently laying the groundwork for the development of standardized elements and formats for computer-based medical information systems. As part of the continuing evolution of the medical record, we foresee these forces culminating in the computerization of the clinical record. In this review, we briefly describe the developments that led us to this conclusion and describe computer-based clinical record systems in use in two family practice settings. PMID- 1431773 TI - Anterior shoulder dislocations. AB - The glenohumeral joint of the shoulder is the most commonly dislocated joint in the body. When dislocation occurs, it is usually anterior. The primary care physician usually sees the patient after reduction has been performed. Thus, treatment is directed at recovery of function and preventing recurrences. The prognosis and likelihood of recurrence in a first-time anterior dislocation depends on the mechanism of injury, treatment, rehabilitation, sex, age, and complications. Non-operative treatment after reduction usually involves immobilization and rehabilitation. Studies to date seem to indicate that age and activity level are more important factors for recurrence than length of immobilization. Traditionally, if there are recurrences after conservative treatment, then surgery is contemplated. PMID- 1431774 TI - Supraventricular tachycardia resistant to treatment in a pregnant woman. AB - Supraventricular tachycardia is relatively common in pregnancy, and is related to the normal physiologic changes of the cardiovascular system in the gravid state. When the arrhythmia is secondary to an ectopic atrial focus of automaticity, it can be particularly difficult to convert to a normal sinus rhythm with medications or DC cardioversion. A case of supraventricular tachycardia complicating a normal pregnancy and resistant to treatment is presented, with particular attention devoted to flecainide and propranolol, agents ultimately effective in this patient. PMID- 1431775 TI - Putting teeth into your physical exam. Part 2: Adults. PMID- 1431776 TI - Sulfoconjugation of steroids and the vascular pathway of communication in dogfish testis. AB - The zonal testis of the dogfish (Squalus acanthias) has proven advantageous to study biochemical changes in relation to stage of spermatogenesis, including information on steroidogenic enzymes and steroid receptors. To investigate whether sulfotransferase is part of a mechanism regulating the availability of biologically active hormone in close proximity to receptors, we measured in vitro conversion of [3H]estrone (E1) to sulfoconjugated metabolites in cytosolic subfractions of testes grossly dissected according to germ cell composition (premeiotic-PrM, meiotic-M, and postmeiotic-PoM stages). Assays were carried out in the presence of adenosine 3'-phosphate 5'-phosphosulfate (PAPS) at 22 degrees C and optimized for time (60 min) and protein (500 micrograms/ml). Michaelis Menten kinetics and saturation analysis gave the following reaction constants for [3H]E1: Km = 0.33 microM, Vmax = 2.5 pmol/min/mg; and for PAPS: Km = 33 microM, Vmax = 1.1 pmol/min/mg; competition studies carried out in the absence or presence of 1- or 5-fold excess radioinert steroids indicated that estrogen (E2 > E1) as well as androgens (T = DHEA > 5 alpha dihydrotestosterone, DHT) were effective inhibitors. Sulfotransferase activity was found to be stage-related, being highest in PoM regions (2.31 +/- 0.24 pmol/min/mg protein) when compared to M and PrM regions (1.22 +/- 0.22 and 1.28 +/- 0.21 pmol/min/mg protein, respectively). Sulfoconjugation and the intratesticular distribution of steroid sulfates were also measured in vivo by perfusion of the intact testis with [3H]androgen or -estrogen. The pathway of blood flow via the genital artery was epigonal organ-->PoM-->M-->PrM (mature-->immature). Perfused [3H]E2, T, and DHT were all extensively metabolized in a one-pass, 1 hr perfusion, less than 10% of perfused [3H] steroid being recovered from testicular tissues as unchanged steroid. In general, recovery of polar metabolites was greater than non-polar metabolites from all three substrates. Sequential hydrolysis with glucuronidase and glusulase indicated that sulfoconjugation is a minor component (< 20%) of several "inactivating" pathways, which include glucuronide conjugation, 17 ketosteroid synthesis, and pathways leading to unidentified polar metabolites. No consistent stage-related distribution patterns were observed for any of the metabolite subfractions; however, total recovered radioactive steroid (polar plus non-polar) formed a decreasing concentration gradient from point of entry of perfusate (PoM region) to point of exit (PrM region). These data support the conclusion that access to receptors by steroid ligands may be controlled by a balance between activating and inactivating pathways.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1431777 TI - Anti-P450lpr antiserum inhibits specific monooxygenase activities in LPR house fly microsomes. AB - Monooxygenase activity in microsomes from the LPR strain of house fly (Musca domestica L.) was inhibited by anti-P450lpr, and antiserum specific for house fly cytochrome P450lpr. Anti-P450lpr did not inhibit house fly cytochrome P450 reductase or rat cytochrome P450 monooxygenase assays, consistent with specific inhibition of P450lpr. Anti-P450lpr inhibited the ability of cytochrome P450 reductase to reduce carbon monoxide treated LPR microsomal cytochrome P450, up to 49% of the total, showing that inhibition of cytochrome P450 reduction is the major mechanism of inhibition. Anti-P450lpr inhibited 98% of methoxyresorufin-O demethylase activity and all the benzo(a)pyrene hydroxylase activity in LPR microsomes, but none of the pentoxyresorufin-O-dealkylase activity. The antiserum partially inhibited ethoxyresorufin-O-dealkylase and ethoxycoumarin-O-dealkylase activity. These results demonstrate that methoxyresourfin-O-demethylase activity and benzo(a)pyrene hydroxylase activity are characteristic substrates for P450lpr activity in the LPR strain of house fly. PMID- 1431778 TI - Inhibitory role of sex steroid in the regulation of ovarian follicle-stimulating hormone receptors during pregnancy. AB - The present study was conducted to determine the role of sex steroids in the regulation of FSH receptors in pregnant rats. In the normal physiological condition, FSH bindings per unit ovarian weight (density of binding) and per 2 ovaries (total binding) increased during days 14-21 gestation. Scatchard plot analyses of the binding suggested that the increase in FSH binding was due to an increase in the number of FSH-binding sites. The plasma FSH concentration in pregnant rats was stable during the receptor change. In contrast, the plasma estradiol-17 beta concentration continuously increased from gestation day 14 to 21, and the testosterone level showed a large peak on gestation day 18. Estradiol 17 beta (one silastic plate containing 13 mg crystal)-implanted pregnant rats during 14-21 days of gestation induced significant decreases in the total FSH binding and ovarian weight on gestation day 21. Estradiol administration increased the plasma estradiol level 2.3-fold but did not change the FSH level. Testosterone or 5 alpha-dihydrotestosterone, a nonaromatizable androgen, did not influence the binding level under the same dose treatment. In contrast, continuous treatment with aminoglutethimide (2 plates containing 20 mg crystal), an inhibitor of adrenocortical steroidogenesis, for 7 days significantly increased the total FSH binding without a significant change in the ovarian weight. The plasma titers of estradiol and testosterone in pregnant rats treated with aminoglutethimide were reduced by 37% and 51%, respectively. Aminoglutethimide did not influence plasma FSH levels. These results suggest that circulating estradiol acts as a negative factor in the regulation of ovarian FSH receptors, at least during the second half of pregnancy. Other factor(s) that is (are) independent of sex steroids and FSH may contribute to FSH receptor induction. PMID- 1431779 TI - Sex differences in adrenal function in the lizard Cnemidophorus sexlineatus: I. Seasonal variation in the field. AB - In order to document sex differences in adrenal function and how this relates to gonadal function during the period of seasonal activity, blood samples from male and female six-lined racerunners, Cnemidophorus sexlineatus, were taken immediately after capture in the field for determination of plasma corticosterone and gonadal steroid concentrations. Plasma testosterone and dihydrotestosterone levels for males, and 17 beta-estradiol and progesterone levels for females, were measured. Trends in the concentration of plasma corticosterone differed significantly between males and females. In males the highest concentrations of corticosterone were measured in late spring and the lowest concentrations were measured in late summer. Whereas half of the variation in corticosterone levels among males could be explained as seasonal change, less than 1% of the variation among females could be explained as seasonal change. In males plasma corticosterone and androgens exhibited similar seasonal decreases. Corticosterone levels for females were not correlated with progesterone or 17 beta-estradiol levels. Sex differences in seasonal variation in plasma corticosterone concentrations suggest that corticosterone may be involved in the different reproductive strategies and energy requirements of males and females during the seasonal period of activity. PMID- 1431780 TI - Sex differences in adrenal function in the lizard Cnemidophorus sexlineatus: II. Responses to acute stress in the laboratory. AB - Circulating concentrations of plasma corticosterone and gonadal steroids were measured in intact and gonadectomized male and female lizards (Cnemidophorus sexlineatus) following acute stress (handling) in the laboratory. There was a significant increase in plasma corticosterone after stress. Whereas intact females exhibited greater concentrations of corticosterone relative to intact males, ovariectomized females exhibited lower concentrations of corticosterone relative to castrated males. In addition to sex differences in corticosterone responses to gonadectomy, progesterone was elevated by stress in both intact and ovariectomized females but not in males. Corticosterone adjusted for castration and handling in males was negatively correlated with the plasma androgen level. The adrenal responsiveness of males to acute stress may be attenuated by androgens presumably secreted by the testis. Not only does adrenal function influence reproduction, but adrenal responses differ between males and females, and appear to be influenced by the gonadal axis. The sex differences in adrenal responses to stress likely reflect different reproductive strategies and nutritional requirements of males and females during the breeding season. PMID- 1431781 TI - Genetic and experimental studies on a new pigment mutant in Xenopus laevis. AB - White lethal (wl) is a recessive mutation affecting the differentiation of the three types of chromatophores in Xenopus laevis and eventually leading to the death of the mutants around stage 50. Melanophores appear at st. 33 but differentiate abnormally, remaining pale grey, and do not proliferate after st. 41. The rare xanthophores present contain only a few differentiated pterinosomes, and the iridophores consist of noniridescent white dots. When the albino gene (ap) is combined with wl, melanophores do not differentiate. Reciprocal heterotopic and orthotopic trunk neural crest grafts have shown that the defect is intrinsic to the neural crest cells but is not due, in the case of melanophores, to a tyrosinase deficiency as revealed by the dopa reaction. The mode of action of the gene, the abnormal pattern, and lethality are discussed. PMID- 1431782 TI - Protein kinase C modulators influence meiosis kinetics but not fertilizability of mouse oocytes. AB - The role of protein kinase C (PKC) in the successive steps of mouse oocyte meiotic process was investigated. We have used either OAG, an analog of diacylglycerol, or mezerein, a nonphorbol ester diterpene, less tumor promoting than phorbol esters, as PKC activators, and staurosporine as PKC inhibitor. Cumulus-free oocytes were cultured in minimum essential medium with each of these PKC modulators and maturation stages were screened every two hours until the end of the process. Both PKC activators prevented GVBD at each tested dose for 4 hr (OAG) and 8 hr (mezerein), and decreased the frequencies of PB oocytes. The inhibitory effects of both activators were dose dependent and reversible. The addition of OAG to the culture medium after GVBD occurrence (i.e., after 4 hrs) did not affect PB extrusion whereas similar addition of mezerein significantly decreased the frequency of PB oocytes. Inhibition of PKC by staurosporine accelerated GVBD and increased the frequency of PB extrusion. When staurosporine was added after GVBD, PB extrusion occurred earlier but PB oocyte frequency was not increased. Fertilizability was not affected when oocyte maturation occurred in the presence of any of these substances despite the delay in maturation process. These results clearly indicate that the PKC pathway is involved in mouse oocyte meiotic process: activation of the enzyme would arrest meiotic process whereas its inhibition would participate in meiosis induction. PMID- 1431783 TI - Culture of postimplantation rat embryos in rabbit serum for the identification of the growth factor in fractionated rat serum. AB - The growth factor for postimplantation rat embryos was investigated on the basis of the serum species-specificity in supporting embryonic development in culture. We used rabbit serum as a basal medium for the culture of head-fold stage rat embryos, and examined the effects of various fractions of rat serum on their development. In rabbit serum alone, rat embryos developed poorly. With the rat serum ultrafiltrate of molecular weight (MW) < 300,000, embryonic development improved, but not with the ultrafiltrate of MW < 100,000. With dialyzed rat serum or the globulin fraction of rat serum, embryonic development improved, but the albumin fraction had no effect. It was concluded from these results that some macromolecular growth factor for cultured postimplantation rat embryos was present in the globulin fraction of rat serum. The molecular weight of this growth factor was estimated to be between 65,000 and 300,000. Rabbit serum was considered to be suitable as a medium for the identification of this growth factor. PMID- 1431784 TI - The ionophore-induced acrosome reaction differs structurally from the spontaneous acrosome reaction. AB - The ultrastructure of the spontaneous acrosome reaction in ram spermatozoa has been compared with that induced by the ionophore, A23187. The spontaneous event was dependent on incubation for 4 h, on the temperature, and on dilution. Apart from the more rapid occurrence of the ionophore-induced event, the mean diameter and distribution of vesicle size was also different. The ionophore-induced vesicles were larger, more irregular, and heterogeneous in size compared with those occurring in the spontaneous acrosome reaction (average diameter 84 nm vs. 60 nm in the spontaneous acrosome reaction). These observations are interpreted in relation to capacitation. PMID- 1431785 TI - The role of hypoglossal sensory feedback during feeding in the marine toad, Bufo marinus. AB - Behavioral observations demonstrate that bilateral deafferentation of the hypoglossal nerves in the marine toad (Bufo marinus) prevents mouth opening during feeding. In the present study, we used high-speed videography, electromyography (EMG), deafferentation, muscle stimulation, and extracellular recordings from the trigeminal nerve to investigate the mechanism by which sensory feedback from the tongue controls the jaw muscles of toads. Our results show that sensory feedback from the tongue enters the brain through the hypoglossal nerve during normal feeding. This feedback appears to inhibit both tonic and phasic activity of the jaw levators. Hypoglossal feedback apparently functions to coordinate tongue protraction and mouth opening during feeding. Among anurans, the primitive condition is the absence of a highly protrusible tongue and the absence of a hypoglossal sensory feedback system. The hypoglossal feedback system evolved in parallel with the acquisition of a highly protrusible tongue in toads and their relatives. PMID- 1431786 TI - Assembly and disassembly of axonal microtubules of the toad Xenopus laevis under the effect of temperature. AB - In toads Xenopus laevis living at 11 degrees (winter), the microtubular density of 4-microns myelinated axons of lumbosacral nerves was assessed with the electron microscope. In controls, the density was 11.2 microtubules/microns2. In nerves incubated at 0 degrees, microtubules decreased following a simple exponential curve with a half time of 4.7 min (k = 0.149 min-1); residual microtubules were 4.5%. After rewarming, the full complement of microtubules reappeared within 60 min. In steady state, the microtubular density exhibited a linear relationship with temperature (range: 0-22 degrees; slope 0.94 microtubules/microns 2 per degree; r, 0.96). After heating the nerve by 11 degrees above the physiological temperature, microtubules increased by 83%, whereby the pool of unpolymerized tubulin was at least 2.7 mg/ml of axoplasm. A seasonal variation of the microtubular density was observed which accorded with the environmental temperature. The macroscopic kinetics of microtubule disassembly in the axoplasm is similar to that reported for purified tubulin but that of assembly is slower. Microtubules of peripheral axons of Xenopus are cold labile and vary during the annual cycle. PMID- 1431787 TI - Formation of the peripheral nervous system during tail regeneration in urodele amphibians: ultrastructural and immunohistochemical studies of the origin of the cells. AB - In the regenerating newt tail, epimorphic regeneration--which recapitulates morphologically normal embryonic development--proceeds along a rostrocaudal differentiation gradient. Innervation of the new myomeres results from the spinal roots of segments rostral to the amputation plane and from ventral roots emerging from the lateroventral region of the regenerating spinal cord, in which motor neurons are differentiating. Electron microscopy and an indirect immunofluorescence study with anti-glial fibrillary acid protein (GFAP) confirm that the ventrolateral part of the regenerated ependymal tube gives rise to cells of the ventral root sheath and the spinal ganglia. Anti-GFAP and anti neurofilament antibodies showed that ependymoglial cells and Schwann cells may play a role in neuronal pathfinding by helping guide and stabilize pioneering axons as they extend toward the myomeres. The carbohydrate epitope NC-1 is expressed in the spinal cord, in sheath cells of the spinal ganglia and in the non-myelin-forming Schwann cells of the peripheral nervous system. L1, a Ca++ independent neural cell adhesion molecule, was detected in the axonal compartments of the regenerating spinal cord, on immature and/or non-myelin forming Schwann cells within the peripheral nervous system (PNS), and on nerve fibers within the regenerate. These immunohistochemical observations collectively support the hypothesis that Schwann cells already present in the blastema could be involved in organizing neural pathways. PMID- 1431788 TI - Pregnancy-associated murine protein-1 (PAMP-1) in wild rodents. AB - The presence of pregnancy-associated murine protein-1 (PAMP-1) in a number of wild rodent species was examined using tandem crossed immunoelectrophoresis and anti PAMP-1 antisera raised in rabbits. PAMP-1 is a protein present in female laboratory mice and rats; analogues were readily detected in the following species: Musculus domesticus, M. musculus, Apodemus sylvaticus, A. agrarius, A. flavicollis, and Microtus arvalus. Immunologically, cross-reacting proteins could not be detected in the laboratory hamster and laboratory guinea pig. Maternal PAMP-1 serum levels were recorded throughout pregnancy in the two species of house mouse: M. domesticus and M. musculus. Both proteins exhibited maximum concentration at day 11 of gestation. During early pregnancy, M. domesticus females had significantly higher serum levels than those of M. musculus females. PMID- 1431789 TI - Planning for discovery. PMID- 1431790 TI - Needed: redefinition of the hospital mission. PMID- 1431791 TI - Initial evaluation of the diving accident victim. AB - Diving accidents include air embolism and decompression sickness. Both require early stabilization and initiation of therapy before transfer to a definitive medical center for recompression therapy. Initial treatment consists of hydration, oxygen therapy and often steroids and antithrombosis therapy. Symptoms must be separated from other related conditions including myocardial infarction. PMID- 1431792 TI - Recreational scuba injuries. AB - Decompression illness, which includes decompression sickness and arterial gas embolism, can be a complex and difficult diagnostic dilemma. The signs and symptoms are not well known and mimic other illnesses which often results in delay when seeking medical evaluation. Additionally, most physicians are not exposed to diving medicine and may not recognize a decompression illness injury. The Divers Alert Network (DAN) offers information to the diving public and telephone consultation for physicians who require assistance in the evaluation of scuba divers and management of dive accident cases. Divers Alert Network also publishes the national annual report on scuba diving morbidity and mortality. Services provided without charge are sponsored by the DAN membership. This article introduces the physician to decompression illness and the basic care and treatment of the injured scuba diver. PMID- 1431793 TI - Pathophysiology and treatment of decompression sickness and gas embolism. AB - Decompression sickness and cerebral gas embolism can present as dramatic and profound sudden onset injuries in patients engaged in tunnel work and compressed gas diving, including scuba. The history and management of these illnesses span centuries. The pathophysiology relates to occurrence of gas bubbles in extrapulmonic sites. Decompression sickness is due to supersaturation of the tissue with dissolved gas and subsequent evolution of gas bubbles. Gas embolism results from the direct transit of molecular gas from a pulmonary or intravascular origin into the arterial circulation causing occlusion of a distal locus. Treatment relates to increasing hydrostatic pressure, thus maximizing the gradient for gas reabsorption and dissolution and subsequently gas excretion via the lungs. PMID- 1431794 TI - Treatment of near drowning. PMID- 1431795 TI - Bodies in water. Solving the puzzle. AB - The enigma produced by a body found in water is clarified only by a total circumstantial investigation correlated with autopsy findings. Multiple factors, human, equipment and environmental, must be considered before opinions are expressed. The conclusion that death is due to drowning does not address the true needs which are to determine why a victim got into difficulty and could not escape. PMID- 1431796 TI - How plastic is the central nervous system? AB - Ramon y Cajal expressed the fatalistic view in 1928, of the central nervous system's response to damage that "...once the development was ended, the fonts of growth and regeneration of the axons and dendrites dried up irrevocably. In adult centers, the nerve paths are something fixed, ended, immutable. Everything may die, nothing may regenerate." Recently, however, new techniques for studying the nervous system have led to a reversal of thought. It is now clear the central nervous system (CNS) is remarkably plastic. While neurons cannot be replaced once they are lost through traumatic damage, the action of neurotoxins or disease processes, remaining neurons are capable of a remarkable array of responses under the appropriate conditions. The lines of research that led to this new concept are briefly explored and also current directions being pursued to understand factors that control CNS plasticity. PMID- 1431797 TI - Beware the hand in the till. PMID- 1431798 TI - Bureaucratic utopia. PMID- 1431799 TI - Youth support card continues to help those in crisis. PMID- 1431800 TI - Expert scientific evidence under the adversarial system. A travesty of justice? AB - The procedures for providing courts with expert scientific evidence under the adversarial and inquisitorial systems are reviewed with special reference to the role of the Home Office as the principal purveyor of such evidence at English law. It is suggested that recent advances in technology must lead to increasing interdependence of the various disciplines involved and that the artificial separations which presently exist, notably between forensic pathology and science, are unsatisfactory. Attention is called to the situation in many European countries where medico-legal institutes provide the courts with comprehensive expert scientific services which are non-confrontational and which do not place experts in the position of appearing for one or other of the parties to an action. PMID- 1431801 TI - Premenstrual tension as mitigation in a criminal case. AB - A woman pleaded guilty to road traffic offences and was sentenced to be disqualified for holding or obtaining a driving licence for six months. Her appeal against that sentence was allowed on the basis that she was suffering from premenstrual tension at the time of the offences, and that the disqualification imposed was neither necessary nor appropriate. PMID- 1431802 TI - The psychology of the terrorist. PMID- 1431804 TI - Gating of O2-sensitive K+ channels of arterial chemoreceptor cells and kinetic modifications induced by low PO2. AB - We have studied the kinetic properties of the O2-sensitive K+ channels (KO2 channels) of dissociated glomus cells from rabbit carotid bodies exposed to variable O2 tension (PO2). Experiments were done using single-channel and whole cell recording techniques. The major gating properties of KO2 channels in excised membrane patches can be explained by a minimal kinetic scheme that includes several closed states (C0 to C4), an open state (O), and two inactivated states (I0 and I1). At negative membrane potentials most channels are distributed between the left-most closed states (C0 and C1), but membrane depolarization displaces the equilibrium toward the open state. After opening, channels undergo reversible transitions to a short-living closed state (C4). These transitions configure a burst, which terminates by channels either returning to a closed state in the activation pathway (C3) or entering a reversible inactivated conformation (I0). Burst duration increases with membrane depolarization. During a maintained depolarization, KO2 channels make several bursts before ending at a nonreversible, absorbing, inactivated state (I1). On moderate depolarizations, KO2 channels inactivate very often from a closed state. Exposure to low PO2 reversibly induces an increase in the first latency, a decrease in the number of bursts per trace, and a higher occurrence of closed-state inactivation. The open state and the transitions to adjacent closed or inactivated states seem to be unaltered by hypoxia. Thus, at low PO2 the number of channels that open in response to a depolarization decreases, and those channels that follow the activation pathway open more slowly and inactivate faster. At the macroscopic level, these changes are paralleled by a reduction in the peak current amplitude, slowing down of the activation kinetics, and acceleration of the inactivation time course. The effects of low PO2 can be explained by assuming that under this condition the closed state C0 is stabilized and the transitions to the absorbing inactivated state I1 are favored. The fact that hypoxia modifies kinetically defined conformational states of the channels suggests that O2 levels determine the structure of specific domains of the KO2 channel molecule. These results help to understand the molecular mechanisms underlying the enhancement of the excitability of glomus cells in response to hypoxia. PMID- 1431803 TI - Mutations in M2 alter the selectivity of the mouse nicotinic acetylcholine receptor for organic and alkali metal cations. AB - We measured the permeability ratios (PX/PNa) of 3 wild-type, 1 hybrid, 2 subunit deficient, and 22 mutant nicotinic receptors expressed in Xenopus oocytes for alkali metal and organic cations using shifts in the bi-ionic reversal potential of the macroscopic current. Mutations at three positions (2', 6', 10') in M2 affected ion selectivity. Mutations at position 2' (alpha Thr244, beta Gly255, gamma Thr253, delta Ser258) near the intracellular end of M2 changed the organic cation permeability ratios as much as twofold and reduced PCs/PNa and PK/PNa by 16-18%. Mutations at positions 6' and 10' increased the glycine ethyl ester/Na+ and glycine methyl ester/Na+ permeability ratios. Two subunit alterations also affected selectivity: omission of the delta subunit reduced PCs/PNa by 16%, and substitution of Xenopus delta for mouse delta increased Pguanidinium/PNa more than twofold and reduced PCs/PNa by 34% and PLi/PNa by 20%. The wild-type mouse receptor displayed a surprising interaction with the primary ammonium cations; relative permeability peaked at a chain length equal to four carbons. Analysis of the organic permeability ratios for the wild-type mouse receptor shows that (a) the diameter of the narrowest part of the pore is 8.4 A; (b) the mouse receptor departs significantly from size selectivity for monovalent organic cations; and (c) lowering the temperature reduces Pguanidinium/PNa by 38% and Pbutylammonium/PNa more than twofold. The results reinforce present views that positions -1' and 2' are the narrowest part of the pore and suggest that positions 6' and 10' align some permeant organic cations in the pore in an interaction similar to that with channel blocker, QX-222. PMID- 1431805 TI - Flash photolysis of caged compounds in Limulus ventral photoreceptors. AB - Rapid concentration jumps of Ins(1,4,5)P3 or ATP were made inside Limulus ventral photoreceptors by flash photolysis of the parent caged compounds. In intact ventral photoreceptors, the photolysis flash evokes a maximum amplitude light activated current; therefore, a procedure was developed for uncoupling phototransduction by blocking two of the initial reactions in the cascade, rhodopsin excitation and G protein activation. Rhodopsin was inactivated by exposure to hydroxylamine and bright light. This procedure abolished the early receptor potential and reduced the quantum efficiency by 325 +/- 90-fold (mean +/ SD). G protein activation was blocked by injection of guanosine-5'-O-(2 thiodiphosphate) (GDP beta S). GDP beta S injection reduced the quantum efficiency by 1,881 +/- 1,153-fold (mean +/- SD). Together hydroxylamine exposure and GDP beta S injection reduced the quantum efficiency by 870,000 +/- 650,000 fold (mean +/- SD). After the combined treatment, photoreceptors produced quantum bumps to light that was approximately 10(6) times brighter than the intensity that produced quantum bumps before treatment. Experiments were performed with caged compounds injected into photoreceptors in which phototransduction was largely uncoupled. Photolysis of one compound, myo-inositol 1,4,5-triphosphate P4(5)-1-(2-nitrophenyl)ethyl ester (caged IP3), increased the voltage clamp current in response to the flashlamp by more than twofold without changing the latency of the response. The effect was not seen with photolysis of either adenosine-5'-triphosphate P3-1-(2-nitrophenyl)ethyl ester (caged ATP) or caged IP3 in cells preloaded with either heparin or (1,2-bis-(o-amino-phenoxy)ethane-N N-N'-N' tetraacetic acid tetrapotassium salt (BAPTA). The results suggest that photoreleased IP3 releases calcium ions from intracellular stores and the resulting increase in [Ca2+]i enhances the amplification of the phototransduction cascade. PMID- 1431806 TI - Synthesis of the complete 200K polyprotein encoded by cowpea mosaic virus B-RNA in insect cells. AB - The coding sequence for the entire 200K polyprotein of cowpea mosaic virus (CPMV) B-RNA was expressed in insect cells by using baculovirus expression vectors. The 200K polyprotein, which harbours all virus functions required for RNA replication, is completely cleaved into 170K and 32K products by the 24K protease activity contained within the polyprotein. Further processing of the 170K protein into CPMV-specific products of 60K, 84K, 87K, 110K and 112K occurred to a limited extent, similar to that observed in cowpea cells. Electron microscopy of insect cells in which the 200K protein was produced revealed the presence of membranous vesicles and electron-dense structures which were not seen in cells infected with wild-type baculovirus. Similar cytopathic structures develop in the cytoplasm of CPMV-infected cowpea cells and are thought to be the site of membrane-bound viral RNA replication. The electron-dense structures in insect cells could be preferentially labelled with several CPMV-specific antisera and Protein A-gold. Since electron-dense structures were not observed in cells in which the 170K protein only was produced, it seems that the 32K protein has a role in keeping the B-RNA-encoded proteins in these structures together. Membranous vesicles were also observed in insect cells in which the 60K protein only was produced. Use of specific antibodies and Protein A-gold showed that the 60K protein is associated with these vesicles, indicating that the 60K protein may induce the formation of vesicles. Although proteolytic processing of the 200K polyprotein and the induction of cytopathic structures indicate that the CPMV proteins produced in insect cells are functional, it has not been possible to demonstrate RNA polymerase activity in extracts of these cells using an oligo(U)-primed assay. The results indicate that in the assay an additional component is lacking and/or that the CPMV polymerase is not able to start RNA synthesis on an exogenous template. PMID- 1431807 TI - The complete nucleotide sequence of turnip mosaic potyvirus RNA. AB - The complete RNA genome of turnip mosaic potyvirus (TuMV) was amplified by seven consecutive reverse transcriptase-polymerase chain reactions and cloned into pUC9. The viral RNA is 9830 nucleotides long and contains a single open reading frame (ORF) of 9489 bases encoding a large polyprotein of 3863 amino acids with a calculated M(r) of 358,000. The non-coding region (NCR) preceding the ORF is 129 nucleotides long and has a high AU content (70%). Its predicted secondary structure is characterized by a hairpin loop with a free energy loss of -69.9 kJ/mol. The termination codon is followed by an AU-rich NCR of 209 bases, excluding the poly(A) tail. Seven potential nuclear inclusion a proteinase (NIa Pro) recognition heptapeptides are found in the polyprotein. Their sequences agree with consensus potyviral NIa-Pro cleavage sequences except for that at the 6K-VPg site, which is characterized by a glutamic acid residue preceding the hydrolysed peptide bond. The TuMV proteins are similar to their corresponding potyviral proteins. PMID- 1431808 TI - The nucleotide sequence of the M RNA segment of tomato spotted wilt virus, a bunyavirus with two ambisense RNA segments. AB - The complete sequence of the tomato spotted wilt virus (TSWV) M RNA segment has been determined. The RNA is 4821 nucleotides long and has an ambisense coding strategy similar to that of the S RNA segment. The M RNA segment contains two open reading frames (ORFs), one in the viral sense which encodes a protein with a predicted size of 33.6K, and one in the viral complementary sense which encodes the precursor to the G1 and G2 glycoproteins, with a predicted size of 127.4K. Both ORFs are expressed via the synthesis of subgenomic mRNAs that possibly terminate at a stable hairpin structure, located in the intergenic region. The precursor for the glycoproteins contains a sequence motif (RGD) which is characteristic of cellular attachment domains. Significant sequence homology was found between the G1 glycoproteins of members of the genus Bunyavirus and a corresponding region in the glycoprotein precursor of TSWV, indicating a close evolutionary relationship between these viruses. With the elucidation of the M RNA sequence, the complete nucleotide sequence of TSWV has been determined. TSWV represents the first member of the Bunyaviridae shown to contain two ambisense RNA segments. PMID- 1431809 TI - Nucleotide sequence and transcriptional analysis of the polyhedrin gene of Spodoptera exigua nuclear polyhedrosis virus. AB - The nucleotide sequence of a 1.1 kbp fragment of the multiple nucleocapsid nuclear polyhedrosis virus (MNPV) of Spodoptera exigua (Se) containing the polyhedrin gene was determined. An open reading frame (ORF) of 738 nucleotides (nt) was detected. This ORF encoded a protein of 246 amino acids with a predicted M(r) of 29K. The nucleotide and amino acid sequences were compared with the sequences of eight other NPV polyhedrins. The SeMNPV polyhedrin protein was most closely related to S. frugiperda MNPV polyhedrin with differences in only five amino acids, and most distantly related to the Lymantria dispar MNPV polyhedrin. The size of the mRNA was approximately 1,000 nt, as determined by Northern blot analysis. Using primer extension assays and S1 nuclease mapping the transcriptional start and stop sites of the polyhedrin mRNA were located. The 5' regulatory sequence appeared to be 44 nt in length with the mRNA start site predominantly at the first A of the TAAG consensus start sequence. Two degenerate poly(A) signals were found immediately downstream of the translational stop signal. The transcriptional stop was located approximately 230 nt downstream from the translational stop signal, in an AT-rich sequence that appears to be common to all baculovirus polyhedrin genes. The SeMNPV polyhedrin mRNA does not appear to be polyadenylated. PMID- 1431810 TI - Fusion of influenza virus particles with liposomes: requirement for cholesterol and virus receptors to allow fusion with and lysis of neutral but not of negatively charged liposomes. AB - Influenza virus particles are able to fuse with liposomes composed of negatively charged or neutral phospholipids, as shown by using fluorochrome-labelled virions and fluorescence dequenching methods. Fusion with liposomes composed of only phosphatidylcholine (PC) was dependent on the presence of cholesterol (Chol), whereas fusion with liposomes containing negatively charged phospholipids, such as phosphatidylserine (PS), or of PC and phosphatidylethanolamine (PE) occurred in the absence of Chol. Fusion of influenza virions with PC:Chol liposomes was observed at pH 5.0, but not at pH 7.4, whereas a low degree of fusion with negatively charged liposomes or those containing PE was observed at pH 7.4. In addition, non-fusogenic influenza virions or HA0 influenza virions fused with PS- or PE-containing liposomes, especially at pH 5.0. Influenza virus particles were also able to induce the release of the fluorochrome calcein from negatively charged calcein-loaded liposomes at pH 5.0, as well as at pH 7.4, but failed to do so with PC:Chol liposomes. Lysis of PC:Chol by influenza virions was dependent on the presence of virus receptors, namely gangliosides (sialoglycolipids), and was observed only at pH 5.0. The results show that fusion of influenza virions with negatively charged or PE-containing liposomes does not reflect the biological activity of the virus needed for penetration and infection of living cells. On the other hand, fusion with PC:Chol liposomes is probably due to the activity of the viral fusion protein, the haemagglutinin glycoprotein. PMID- 1431811 TI - Analysis of a 9.6 kb sequence from the 3' end of canine coronavirus genomic RNA. AB - We have analysed the organization of the 3' end of the genomic RNA of canine coronavirus (CCV), a virus which has a close antigenic relationship to transmissible gastroenteritis virus (TGEV), porcine respiratory coronavirus (PRCV) and feline infectious peritonitis virus (FIPV). Genomic RNA isolated from CCV strain Insavc-1-infected A72 cells was used to generate a cDNA library. Overlapping clones, spanning approximately 9.6 kb [from the 3' end of the polymerase gene, 1b, to the poly(A) tail] were identified. Sequencing and subsequent analyses revealed 10 open reading frames (ORFs). Three of these code for the major coronavirus structural polypeptides S, M and N; a fourth codes for a small membrane protein, SM, a putative homologue of the IBV structural polypeptide 3c, and five code for polypeptides, designated 1b, 3a, 4, 7a and 7b, homologous to putative non-structural polypeptides encoded in the TGEV or FIPV genomes. An extra ORF which had not hitherto been identified in this antigenic group of coronaviruses was designated 3x. Pairwise alignment of these ORFs with their counterparts in TGEV, PRCV and FIPV revealed high levels of identity and highlighted the close relationship between the members of this group of viruses. PMID- 1431812 TI - Open reading frames 1 and 2 of adenovirus region E4 are conserved between human serotypes 2 and 5. AB - The E4 region of human adenovirus type 2 is predicted to encode seven proteins as judged from its nucleotide sequence and the pattern of differential splicing of its transcript. Two of the open reading frames (ORFs), ORF1 and ORF2, had been identified as being disrupted in the recently published sequence of the related serotype 5 virus. These ORFs were resequenced and found to be intact in the wt300 strain of adenovirus type 5. PMID- 1431813 TI - Sequences responsible for efficient replication of simian immunodeficiency virus SIVMND in cells of the monocyte/macrophage lineage. AB - We determined the susceptibility of monocytic cell lines to infection with viral strains derived from two infectious clones of simian immunodeficiency virus isolated from a mandrill. One of the strains, which replicates poorly in T cell lines, was found to grow more rapidly than the other in these cells. The viral determinant for this property was genetically mapped within the env gene encoding a surface protein. Six amino acid substitutions identified appeared to be located outside of the domains corresponding to human immunodeficiency virus type 1 env functional domains such as the CD4-binding and V3 loop regions. PMID- 1431815 TI - Intracellular distribution of the 126K/183K and capsid proteins in cells infected by some tobamoviruses. AB - Leaves of plants infected by tobacco mosaic virus (TMV) strain U1, TMV strain M, tomato mosaic virus strain Dahlemense and tobacco mild green mosaic virus strain U2 were examined for the presence and intracellular distribution of their capsid and 126K/183K proteins by immunoblotting and immunogold electron microscopy. The bulk of the capsid protein was found in the virus bundles (crystals), although small amounts were found in the chloroplasts and nuclei of cells infected by some of these tobamoviruses. The 126K protein of TMV-U1 and -M was localized in the X bodies, whereas in cells infected by the other two viruses which induce no X bodies, the 126K protein was found to be associated with virus bundles. PMID- 1431814 TI - Genomic variability in the preS1 region and determination of routes of transmission of hepatitis B virus. AB - On the basis of published sequence data the preS1 attachment region of hepatitis B virus (HBV) appears to be highly variable. Using a novel method for rapid DNA sequencing by the polymerase chain reaction we screened 34 HBV DNA-positive sera for mutations in a variable part of the preS1 region of the HBV genome. The sequence data were used to analyse potential chains of infection, and strongly supported the expected routes of HBV transmission among patient groups. Furthermore, sequence comparisons permitted sub-genotyping of the viruses. In the 22 cases of subtype adw, we found a very low number of point mutations. This shows that the attachment site of HBV is more highly conserved than that of other blood-transmissible viruses such as human immunodeficiency virus or hepatitis C virus. PMID- 1431816 TI - Diffraction studies of the particles of two closteroviruses: heracleum latent virus and heracleum virus 6. AB - X-ray diffraction from oriented specimens of purified preparations of particles of heracleum latent closterovirus (HLV) showed that they have a helical arrangement of protein subunits, and that the structure repeats in five helical turns in which there are 5q +/- 1 protein subunits, where q is an integer. The pitch of the helix was estimated to be 3.26 (+/- 0.10) nm. Optical diffraction patterns from electron micrographs of HLV particles give an estimated pitch of 3.3 (+/- 0.2) nm and show that the number of subunits in the repeat period is 5q 1, where q has a value of 8 or 9. Optical diffraction from electron micrographs of particles of a second closterovirus, heracleum virus 6, shows that they too have a helical structure which repeats in five turns, in which there are 5q +/- 1 protein subunits. The estimated pitch of the primary helix is 3.6 (+/- 0.2) nm, and the estimate of q is 9. PMID- 1431817 TI - Complete sequence of maize stripe virus RNA4 and mapping of its subgenomic RNAs. PMID- 1431818 TI - Respiratory syncytial virus detection by dot blot hybridization with a nonradioactive synthetic oligo deoxynucleotide probe. AB - A synthetic oligodeoxynucleotide corresponding to a region of the nucleocapside gene (N) of respiratory syncytial virus (RSV), was used as a DNA probe to develop a nonradioactive hybridization assay for the detection of RSV. The probe was labeled by incorporation of biotin-7-dATP to the 3' end by a reaction catalyzed by terminal deoxynucleotydil transferase. The dot blot hybridization assay was found to be specific for RSV when tested against RSV isolates (subgroups A and B) obtained from cell cultures and isolates of adenovirus, reovirus, rotavirus, and pararotavirus. The assay detected both RSV subgroups (A and B) without significant differences. The dot blot hybridization assay using the nonradioactive probe led to similar results to indirect immunofluorescence (IFI) when tested against a panel of 64 clinical samples from nasopharyngeal secretions of infants with clinical symptoms of respiratory disease. This assay may provide the basis for a rapid, simple, and inexpensive method for routine RSV diagnosis. PMID- 1431819 TI - Toward a more culturally sensitive DSM-IV. Psychoreligious and psychospiritual problems. AB - In theory, research, and practice, mental health professionals have tended to ignore or pathologize the religious and spiritual dimensions of life. This represents a type of cultural insensitivity toward individuals who have religious and spiritual experiences in both Western and non-Western cultures. After documenting the "religiosity gap" between clinicians and patients, the authors review the role of theory, inadequate training, and biological primacy in fostering psychiatry's insensitivity. A new Z Code (formerly V Code) diagnostic category is proposed for DSM-IV: psychoreligious or psychospiritual problem. Examples of psychoreligious problems include loss or questioning of a firmly held faith, and conversion to a new faith. Examples of psychospiritual problems include near-death experiences and mystical experiences. Both types of problems are defined, and differential diagnostic issues are discussed. This new diagnostic category would: a) improve diagnostic assessments when religious and spiritual issues are involved; b) reduce iatrogenic harm from misdiagnosis of psychoreligious and psychospiritual problems; c) improve treatment of such problems by stimulating clinical research; and d) encourage clinical training centers to address the religious and spiritual dimensions of human existence. PMID- 1431820 TI - Neurobehavioral aspects of postconcussive symptoms after mild head injury. AB - The sequelae of severe closed head injury have received much attention in the literature, but the effects of mild closed head injury (MHI) are less well established. There is a subgroup of patients who complain of persisting postconcussive symptoms (PCS) beyond the first weeks of recovery. Although the symptoms generally develop in the absence of clear neurological abnormalities, the condition of PCS can be chronic and disabling. It has been assumed that PCS result from an interaction between organic and psychological factors. Differentiating between the effect of primary neurological injury and secondary psychosocial problems is often difficult for clinicians and engenders controversy. Neuropsychological, neurophysiological, and neuroimaging measures can be helpful in selecting patients at risk of developing PCS. Assessment of the level of cognitive functioning, individual susceptibility to stress, and environmental demands may be beneficial in treating symptomatic patients. It is true that the vague and aspecific nature of the postconcussion syndrome may have given rise to the controversy over this entity, but the many methodological inconsistencies in the experimental approaches to the syndrome have certainly enhanced the confusion about this issue. The ensuing controversy surrounding research on the outcome of MHI and the postconcussion syndrome reflects ambiguities in definition, inconsistencies in criteria for patient selection, variation in procedures for neurobehavioral assessment, and difficulty in obtaining follow-up data. PMID- 1431821 TI - Predicting the course of melancholic and nonmelancholic depression. A naturalistic comparison study. AB - We assessed improvement patterns and predictors of outcome over a 1-year period, in a sample of depressed patients receiving treatment from a specialized mood disorders unit. Patients with melancholia had a differential improvement pattern from the nonmelancholics in the first 20 weeks, but case rates and severity levels were comparable at 20 weeks and at 1 year. Only three variables (older age at first episode, less severe depression and extraversion) were predictors of improvement in both groups. Improvement was predicted by less psychomotor disturbance, absence of personality disorder, and higher social functioning in the melancholic patients. A reported absence of timidity and shyness in childhood, a briefer duration of depression, and receipt of individual psychotherapy predicted a better outcome in the nonmelancholic patients. Although significant predictors were few overall, the suggested differential relevance for most of the isolated predictors argues for outcome studies that examine melancholic and nonmelancholic depressive disorders separately. PMID- 1431822 TI - Emotion differentiation. A correlate of symptom severity in major depression. AB - The relationship of emotion differentiation to symptom severity in depression was investigated. The subjects were 25 patients diagnosed with unipolar major depression. Subjects were clinically assessed using the Schedule for Affective Disorders and Schizophrenia and the Hamilton rating scales for anxiety and depression. In addition, subjects completed a number of self-report measures of symptoms and attitudes. Twelve basic emotion terms were incorporated into free response attribute lists which subjects used to rate aspects of themselves and of other significant people in their lives. A clustering algorithm (HICLAS) was used to derive a social perception structure from this data for each subject. The differentiation of negative emotion within an individual's structure (NES) was measured by dividing the number of attribute categories containing negative emotions by the total number of categories in that person's structure. The results indicated that NES is a significant correlate of depressive symptomatology independent of self-esteem and other variables. Relatively undifferentiated emotion structure (low NES) was associated with significantly higher levels of depressive symptomatology. PMID- 1431823 TI - Bipolar II affective disorder in eating disorder inpatients. AB - We examined the association between affective disorders and eating disorders in 22 eating disorder inpatients who were interviewed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. The first series of 11 were interviewed as part of an interrater reliability study; the second series, done as follow-up to the first, consisted of 11 consecutive admissions. Overall, there were 15 bulimics and seven anorexics. Nineteen patients had a major affective disorder, and 13 (59%) had bipolar II affective disorder. Bipolar II affective disorder appears to be a common finding in hospitalized patients with severe persistent eating disorders. PMID- 1431824 TI - The Positive and Negative Syndrome Scale and the Brief Psychiatric Rating Scale. Reliability, comparability, and predictive validity. AB - In a psychiatric rehabilitation study, 154 concurrent ratings were performed using the 30-item Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS). Although both instruments had excellent interrater reliability, the PANSS was consistently better: on the 18 symptom items the two instruments share, the PANSS had higher intraclass r's on 14; for the syndromes, the PANSS was higher than the BPRS on positive, negative, and total. Weighted Kappas comparing shared items revealed that most were not interchangeable, with only three coefficients in the excellent range. However, syndrome scale scores were very highly correlated and resulted in similar classification for negative schizophrenia. Ten of the 12 items of the PANSS not included in the BPRS had low zero-order correlations with BPRS items, which suggests that they measure symptoms distinct from those measured by the BPRS and should add to clinical predictive power. This proved true in our study of rehabilitation of patients with schizophrenia. PANSS symptom ratings explained up to 55% of the variance on seven measures of work performance, whereas the BPRS had lower predictive power on six of the seven measures. We concluded that the PANSS may be superior to the BPRS in clinical research on schizophrenia and that most BPRS items are not interchangeable with identically named PANSS items. PMID- 1431825 TI - An association between domestic violence and depression among Southeast Asian refugee women. PMID- 1431826 TI - Cognitive impairment and depression in mild multiple sclerosis. PMID- 1431827 TI - Phenobarbital exacerbation of self-injurious behavior. PMID- 1431828 TI - Delusional misidentification of Capgras: a case report from Oman. PMID- 1431829 TI - Naltrexone abuse potential. PMID- 1431830 TI - Personality characteristics and posttraumatic stress symptoms after a school shooting. PMID- 1431831 TI - Anxiety sensitivity distinguishes panic disorder from generalized anxiety disorder. PMID- 1431833 TI - Views on regeneration in the nervous system. PMID- 1431832 TI - Response to Ross and Joshi. PMID- 1431834 TI - GAP-43 as a plasticity protein in neuronal form and repair. AB - Neurons exhibit a remarkable plasticity of form, both during neural development and during the subsequent remodelling of synaptic connectivity. Here we review work on GAP-43 and G0, and focus upon the thesis that their interaction may endow neurons with such plasticity. We also present new data on the role of G proteins in neurite growth, and on the interaction of GAP-43 and actin. GAP-43 is a protein induced during periods of axonal extension and highly enriched on the inner surface of the growth cone membrane. Its membrane localization is primarily due to a short amino terminal sequence which is subject to palmitoylation. Binding to actin filaments may also assist in restricting the protein to specific cellular domains. Consistent with its role as a "plasticity protein," there is evidence that GAP-43 can directly alter cell shape and neurite extension, and several theses have been advanced for how it might do so. Two other prominent components of the growth cone membrane are the alpha and beta subunits of G0. GAP 43 regulates their guanine nucleotide exchange, which is an unusual role for an intracellular protein. We speculate that GAP-43 may adjust the "set point" of responsiveness for G0 stimulation by receptors, thereby altering the neuronal propensity to growth, without actually causing growth. To begin to address how G protein activity affects axon growth, we have developed a means to introduce guanine nucleotide analogs into sympathetic neurons. Stimulation of G proteins with GTP-gamma-S retards axon growth, whereas GDP-beta-S enhances it. This is compatible with G protein registration of inhibitory signals. PMID- 1431835 TI - Consequences of slow Wallerian degeneration for regenerating motor and sensory axons. AB - The time course of Wallerian degeneration in the tibial and saphenous nerves was compared in Balb/c mice and mice of the C57BL/Ola strain (Lunn et al., 1989). Axons, particularly myelinated ones, in nerves of C57BL/Ola mice are very slow to degenerate, many still being present 3 weeks after axotomy. Nuclear numbers in the distal stump peak much later and do not reach the levels found in Balb/c mice; debris removal is very slow, and Schwann cell numbers only rise slightly above normal levels in the long term. Regeneration was investigated electrophysiologically and by electron microscopy (EM). Myelinated sensory axons regenerated slowly and incompletely compared with motor ones which were only slightly slowed after nerve crush (although they were significantly hindered after nerve section). Total myelinated axon numbers were still some 20% less than normal even after 200 days in sensory nerves. Even after all axons had degenerated in C57BL/Ola mice, regeneration rates of neither myelinated nor unmyelinated sensory axons reached those achieved in Balb/c mice. It is concluded that while regeneration can eventually proceed slowly when Wallerian degeneration is much delayed, the usual rapid time course of Wallerian degeneration is necessary if axons, particularly sensory ones, are to regenerate at optimal rates and to maximum extent. While local obstruction to axon growth probably impedes the early phase of regeneration in C57BL/Ola mice, it seems possible that a lack of adequate early signals affects regeneration permanently by minimizing the cell body reaction to injury. PMID- 1431836 TI - Trying to understand axonal regeneration in the CNS of fish. AB - In contrast to the situation in mammals and birds, neurons in the central nervous system (CNS) of fish--such as the retinal ganglion cells--are capable of regenerating their axons and restoring vision. Special properties of the glial cells and the neurons of the fish visual pathway appear to contribute to the success of axonal regeneration. The fish oligodendrocytes lack the axon growth inhibiting molecules that interfere with axonal extension in mammals. Instead, fish optic nerve oligodendrocytes support--at least in vitro--axonal elongation of fish as well as that of rat retinal axons. Moreover, the fish retinal ganglion cells re-express upon injury a set of growth-associated cell surface molecules and equip the regenerating axons throughout their path and up into their target, the tectum opticum with these molecules. This may indicate that the injured fish ganglion cells reactivate the cellular machinery necessary for axonal regrowth and pathfinding. Furthermore, the target itself provides positional marker molecules even in adult fish. These marker molecules are required to guide the regenerating axons back to their retinotopic home territory within the tectum. PMID- 1431837 TI - Specificity of a target cell-derived stop signal for afferent axonal growth. AB - With a novel model culture system in which afferents are co-cultured with purified populations of target neurons, we have demonstrated that a target cell within the central nervous system (CNS), the cerebellar granule neuron, poses a "stop-growing signal" for its appropriate afferents, the mossy fibers. To ask whether this stop signal is afferent specific, we co-cultured granule neurons with another cerebellar afferent system, the climbing fibers from the inferior olivary nuclei, which normally contact Purkinje neurons, and with retinal ganglion cell afferents, which never enter the cerebellum. Granule neurons do not pose a stop signal to either of these afferents. In contrast to pontine mossy afferents that grow well on laminin and showed reduced outgrowth on granule neurons, both olivary and retinal fibers displayed similar growth on laminin alone or on granule neurons. In addition, each afferent showed different degrees of fasciculation and growth cone morphology on laminin. Thus, the growth arrest signal sent by granule neurons is specifically recognized by their appropriate afferents. Moreover, these three types of afferents exhibit varying growth patterns on the same noncellular and cellular substrates, implicating distinct molecular characteristics of growth regulation for different classes of neurons that would contribute to specificity of synapse formation. PMID- 1431838 TI - Degeneration of photoreceptors in rhodopsin mutants of Drosophila. AB - Five different, well-characterized mutants of the R1-6 rhodopsin gene (ninaE), which corresponds to the rod opsin gene of vertebrates, have been examined morphologically as a function of age (up to 9 weeks) to determine whether or not the photoreceptors degenerate and to assess the pattern of degeneration. Structural deterioration of R1-6 photoreceptors with age has been found in all five mutants. The structural pattern of degeneration is similar in the five mutants, but the time course of degeneration is allele dependent and varies greatly among the five, with the strongest alleles causing the fastest degeneration. The degeneration appears to be independent of either the illumination cycle to which the animals are exposed or the presence of screening pigments in the eye. Although the degeneration first appears in R1-6 photoreceptors, eventually R7/8 photoreceptors, which correspond to cones of vertebrates, are also affected. In many of these mutants, striking proliferations of membrane processes have been observed in the subrhabdomeric region of R1-6 photoreceptors. It is hypothesized that (1) this accumulation of membranes may be caused by the failure of newly synthesized membranes that are inserted into the base of microvilli to be assembled into R1-6 rhabdomeres and (2) this failure may be caused by the extremely low concentration of normal R1-6 rhodopsin in the ninaE mutants. PMID- 1431839 TI - Dopamine and nicotine, but not serotonin, modulate the crustacean ventilatory pattern generator. AB - Dopamine (DA) causes a dose-dependent increase in the frequency of motor neuron bursts [virtual ventilation (fR)] produced by deafferented crab ventilatory pattern generators (CPGv). Domperidone, a D2-specific DA antagonist, by itself reversibly depresses fR and also blocks the stimulatory effects of DA. Serotonin (5HT) has no direct effects on this CPGv. Nicotine also causes dramatic dose dependent increases in the frequency of motor bursts from the CPGv. The action is triphasic, beginning with an initial reversal of burst pattern typical of reversed-mode ventilation, followed by a 2- to 3-min period of depression and then a long period of elevated burst rate. Acetylcholine chloride (ACh) alone is ineffective, but in the presence of eserine is moderately stimulatory. The inhibitory effects of nicotine are only partially blocked by curare. The excitatory action of nicotine is blocked by prior perfusion of domperidone, but not by SKF-83566.HCl, a D1-specific DA antagonist. SKF-83566 had no effects on the ongoing pattern of firing. These observations support the hypothesis that dopaminergic pathways are involved in the maintenance of the CPGv rhythm and that the acceleratory effects of nicotine may involve release of DA either directly or via stimulation of atypical ACh receptors at intraganglionic sites. PMID- 1431840 TI - Ipsilateral retinal projections into the tectum during regeneration of the optic nerve in the cichlid fish Haplochromis burtoni: a Dil study in fixed tissue. AB - Retinal projections were experimentally manipulated in a bony fish to reveal conditions under which considerably enlarged ipsilateral projections developed and persisted. Three experimental groups were studied: animals after unilateral enucleation, after unilateral nerve crush, and after enucleation and crush of the remaining optic nerve. At 29 days after unilateral enucleation alone, no enhanced ipsilateral projection had developed. After nerve crush, however, large numbers of retinal fibers regenerated into the ipsilateral tectum. Retrogradely filled, ipsilaterally projecting ganglion cells were distributed throughout the entire retina. After 15 days regenerating retinal fibers covered the entire ipsilateral tectum. At later stages the ipsilateral projection showed progressive reduction in coverage of the tectum. Combining enucleation with nerve crush led to an ipsilateral projection that covered the tectum at 28 days and later. In this experimental situation the development of an ipsilateral projection appears to be a two-step process: (1) Fibers are rerouted to the ipsilateral side at the diencephalon, and (2) ipsilateral fibers persist in the tectum only in the absence of a contralateral projection while they appear to be eliminated in the other cases. PMID- 1431841 TI - The development of ipsilateral retinal projections into the tectum in the cichlid fish Haplochromis burtoni: a Dil study in fixed tissue. AB - The normal development of the retinal projection was studied in a bony fish with Dil. Between 5.5 and 10 days postfertilization the contralateral retinal projection grows from the rostral pole of the tectum across its center. A maximum of 15 retinal fibers reaches the ipsilateral tectum. In 33-day-old juvenile animals, less than 15 ipsilateral fibers terminate in the entire tectum. Ipsilaterally projecting ganglion cells (maximal number = 20 cells) are scattered throughout the entire retina, and the location of ganglion cells in the retina and axonal terminations in the tectum display a large interindividual variability. This suggests that the small adult contingent of ipsilateral fibers in this bony fish develops without an initial exuberant ipsilateral retinal projection that is later pruned back. PMID- 1431842 TI - Transient expression of adheron molecules during chick retinal development. AB - Neuritogenesis and synapse formation are transient phenomena mediated in part by filopodial attachments (Tsui, Lankford, and Klein, Proc. Natl. Acad. Sci. 82:8256 8260 1985). The attachments can be labeled by antisera against adherons, adhesive microparticles isolated from cell culture media (Tsui, Schubert, and Klein, J. Cell Biol. 106:2095-2108 1988). Here, two monoclonal antibodies raised against adherons have been found to recognize transiently expressed membrane antigens of developing avian retina. Early in development, monoclonal antibody (mAb) AD1 stained antigens that spanned the entire tissue. With time, immunoreactivity became restricted to optic fiber, ganglion cell, and inner plexiform layers. Immunoblots of embryonic day (E) 13 retina showed a broad band at 66-72 kD for particulate fractions and a fine band at 70 kD for soluble fractions. The particulate forms disappeared as retinas matured, but the soluble form did not. mAb AD2 initially labeled retina antigens of optic fiber, ganglion cell, and inner plexiform layers (IPL). Labeling in the plexiform layer showed discrete lamina. Immunoreactivity first appeared at E9, peaked at E15, and then disappeared shortly after hatching. In isolated cells, AD2 labeled small cell surface aggregates. Cytoarchitectural studies, using whole-mount transmission electron microscopy, showed AD2 antigen in cell surface microfilaments, including some that joined filopodia together. The adheron antigens recognized by mAbs AD1 and AD2 thus were (1) topographically restricted; (2) associated with cell surfaces; and (3) developmentally down-regulated. This pattern suggests a role in developmentally transient cell surface phenomena, such as neurite extension or junction biogenesis. PMID- 1431843 TI - Modulation of growth of Aplysia neurons by an endogenous lectin. AB - We have purified and characterized a galactose-binding lectin from the gonads of the mollusk Aplysia californica that modulates neurite outgrowth from cultured Aplysia neurons. Agglutination of sheep red blood cells (RBC) by this lectin, termed Aplysia gonad lectin (AGL), is inhibited strongly by galactose and to a lesser extent by fucose. On SDS-PAGE, AGL appears as a single species with a molecular weight of 34 kD under reducing conditions, and 65 kD under nonreducing conditions. This suggests that AGL is a disulfide-linked dimer in its native state. Amino terminal sequence analysis of purified AGL indicates a similarity to another galactose-binding lectin, phytohemagglutinin-E (E-PHA), found in red kidney beans. By using polyclonal antibodies prepared against AGL, we have found that the lectin is present in the gonads and eggs but not in other tissues of adult Aplysia californica. We have examined biological actions of AGL on Aplysia neurons growing in primary cell culture. AGL affects several properties of these neurons. The addition of 100 nM AGL to cultured neurons enhances neurite outgrowth from the cell soma, resulting in a greater number of primary processes. In addition, AGL acts as a neurotrophic agent, increasing neurite viability in vitro. This trophic effect is not seen with concanavalin A (con A), another lectin known to affect several properties of cultured Aplysia neurons. The results are consistent with the suggestion that AGL may play a role in neuronal differentiation and/or maintenance of viability. PMID- 1431844 TI - Modification of the dystrophic phenotype after transient neonatal denervation: role of MHC isoforms. AB - While it recently has been demonstrated that it is possible to modify the phenotypic expression of murine dystrophy (dy/dy) (i.e., prevent myofiber loss) by subjecting the extensor digitorum longus (EDL) muscle of 14-day-old dy/dy mice to transient neonatal denervation (Moschella and Ontell, 1987), the mechanism responsible for this phenomenon has not been determined. Since it has been suggested that the effects of dystrophy vary according to fiber type, the fiber type frequency in 100-day-old normal (+/+) and dy/dy EDL muscles subjected to transient neonatal denervation has been determined by immunohistochemical analysis of their myosin heavy chain (MHC) composition. This frequency has been compared with that found in the EDL muscles of 14- and 100-day-old unoperated +/+ and dy/dy mice, in order to determine whether the reinnervation of transiently denervated neonatal muscle results in a preponderance of fibers of the type that might be spared dystrophic deterioration. In unoperated dy/dy muscle there is a progressive decrease in the frequency and in the absolute number of fibers that express MHC2B, with 100-day-old dy/dy muscles having approximately 32% of the number of myofibers fibers containing MHC2B as is found in age-matched +/+ muscles. The number of fibers containing the other fast isoforms (MHC2A and MHC2X) is similar in +/+ and dy/dy muscles at this age, indicating that fibers with MHC2B are most affected by the dystrophic process. Reinnervation following transient neonatal denervation of both the +/+ and the dy/dy EDL muscles results in a similar decrease (approximately 62%) in the number of myofibers containing MHC2B and an increase in myofibers containing the other fast MHC isoforms (MHC2A and MHC2X). The selective effect of dy/dy on fibers containing MHC2B and the sparing of myofibers in transiently denervated dy/dy muscle (which contains a reduced frequency of fibers containing MHC2B) are consistent with, although not direct proof of, the hypothesis that alterations in the fiber type may play a role in the failure of myofibers in transiently denervated dy/dy muscles to undergo dystrophic deterioration. Evidence is presented suggesting that neurons that supply myofibers containing MHC2B may be at a selective disadvantage in their ability to reinnervate neonatally denervated muscles. PMID- 1431845 TI - Formation and preservation of cortical layers in slice cultures. AB - During cortical development, neurons generated at the same time in the ventricular zone migrate out into the cortical plate and form a cortical layer (Berry and Eayrs, 1963, Nature 197:984-985; Berry and Rogers, 1965, J. Anat. 99:691-709). We have been studying both the formation and maintenance of cortical layers in slice cultures from rat cortex. The bromodeoxyuridine (BrdU) method was used to label cortical neurons on their birthday in vivo. When slice cultures were prepared from animals at different embryonic and postnatal ages, all cortical layers that have already been established in vivo remained preserved for several weeks in vitro. In slice cultures prepared during migration in the cortex, cells continued to migrate towards the pial side of the cortical slice, however, migration ceased after about 1 week in culture. Thus, cortical cells reached their final laminar position only in slice cultures from postnatal animals, whereas in embryonic slice, migrating cells became scattered throughout the cortex. Previous studies demonstrated that radial glia fibers are the major substrate for migrating neurons (Rakic, 1972, J. Comp. Neurol. 145:61-84; Hatten and Mason, 1990, Experientia 46:907-916). Using antibodies directed against the intermediate filament Vimentin, radial glial cells were detected in all slice cultures where cell migration did occur. Comparable to the glia development in vivo, radial glial fibers disappeared and astrocytes containing the glia fibrillary-associated protein (GFAP) differentiated in slice cultures from postnatal cortex, after the neurons have completed their migration. In contrast, radial glial cells were detected over the whole culture period, and very few astrocytes differentiated in embryonic slices, where cortical neurons failed to finish their migration. The results of this study indicate that the local environment is sufficient to sustain the layered organization of the cortex and support the migration of cortical neurons. In addition, our results reveal a close relationship between cell migration and the developmental status of glial cells. PMID- 1431846 TI - A real-time analysis of growth cone-target cell interactions during the formation of stable contacts between hippocampal neurons in culture. AB - Mechanisms of cell-cell recognition and structural changes of growth cones (g.c.) and target membranes during contact formation are poorly understood. To examine these issues, we obtained a high magnification, real-time record of stable contact formation in cultured cells from the hippocampal CA1 area in the newborn rat. We used differential interference contrast (DIC) optics coupled to a video microscope for periods of over 24 h of continuous time-lapse recording. Our goal was to observe the sequential changes exhibited by afferent and target cells as they form a stable contact. Understanding the process of how stable contacts are made is important because such contacts are the first step in synapse formation. Four principal observations emerged from our study: (1) The target cell was receptive to a contact on a specific patch on its surface defined by the presence of lamellae and filopodia. This specific patch (named target site) was invariably present on the target cell surface before the time the growth cone arrived. (2) Stable adhesion between filopodia on the two cells initiated events leading to cell-cell contact formation. Specifically, the remaining filopodia on the growth cone and target cell were redirected toward the adhering filopodia, and the growth cone size decreased dramatically. (3) The axonal process then grew at a significantly accelerated rate (up to 50 times its baseline growth rate). (4) In addition, a number of observations were obtained on axonal turns towards the target cell, induction of target sites, and architectural remodelling of cells after the formation of a new contact. Our findings indicate that in this neuronal system, filopodia are the means used by cells to interact at stages prior to and during contact formation. We speculate that the molecules involved in cell recognition and the machinery that initiates contact formation are embedded in the fine structure of filopodia. Finally, our results provide possible clues as to some of the stages that may be involved in synapse formation in the mammalian central nervous system. PMID- 1431847 TI - Patterns of serotonin and SCP immunoreactivity during metamorphosis of the nervous system of the red abalone, Haliotis rufescens. AB - Larvae of the red abalone, Haliotis rufescens, rely on external chemical cues to trigger metamorphosis; thus, the timing of metamorphosis is dependent upon the larva's chance encounter with the appropriate substrate. We examined the effect of the timing of metamorphosis on the development of the central nervous system (CNS), concentrating on the pattern of serotonin and small cardioactive peptide- (SCP) immunopositive neurons in the cerebral ganglia. By 4 days postfertilization the cerebral ganglion has five pairs of serotonin-immunoreactive (IR) neurons, one pair of which (the V cells) innervate the velum. This complement of cells remains stable for as long as the larval stage persists but metamorphosis causes the rapid loss of the V cells. In the case of SCP-IR neurons, one pair is present prior to metamorphic competency, but as larvae continue to age in the absence of inducing cues, additional pairs are gradually added. Metamorphosis causes an acceleration in SCP-IR neuron addition. This separation of developmental patterns is well adapted for the inherent uncertainty of the timing of metamorphosis in abalone larvae. PMID- 1431848 TI - A specific brain tract guides follower growth cones in two regions of the zebrafish brain. AB - Neurons of the nucleus of the posterior commissure (nuc PC), an identifiable cluster of neurons in the embryonic zebrafish brain, project growth cones ventrally along the posterior commissure to the anterior tegmentum where the PC intersects two longitudinal tracts, the tract of the postoptic commissure (TPOC) and the medial longitudinal fasciculus (MLF). Once at the intersection, nuc PC growth cones turn posteriorly onto the TPOC in the dorsal tegmentum and follow it to the hindbrain. Previously we showed that in the absence of the TPOC, nuc PC growth cones often extended along aberrant pathways suggesting that fasciculation, that is, contact with TPOC axons is an important factor in guiding growth cones along their normal pathway. However, a significant number of nuc PC growth cones also followed their normal pathway suggesting that cues associated with the dorsolateral tegmentum, independent of the TPOC, can also guide nuc PC growth cones. We have now confirmed using electron microscopy that nuc PC growth cones fasciculate with axons in the TPOC. In the absence of the TPOC, the nuc PC growth cones that extend along their normal pathway do so in contact with dorsolateral neuroepithelial cells. This suggests that cues associated with these cells can also guide the nuc PC growth cones. Furthermore, in the absence of the TPOC axons, these growth cones now inappropriately turn onto axons that normally intersect the TPOC near the border of the midbrain and hindbrain, that is, at a second intersection of tracts. This suggests that fasciculation with TPOC axons may also guide nuc PC growth cones in this second region of the brain. PMID- 1431849 TI - Hormone accumulation in song regions of the canary brain. AB - [3H]Testosterone (T) was injected into male and female canaries (Serinus canarius), a species in which females are able to sing but do so more rarely and more simply than males. Autoradiographic analysis revealed that males and females have equal proportions of cells labeled by T or its metabolites in four song control nuclei: the high vocal center (HVC), the lateral portion of the magnocellular nucleus of the anterior neostriatum (IMAN), the robust nucleus of the archistriatum (RA), and the hypoglossal motor nucleus (nXII). Labeled cells were also observed in both sexes in the medial portion of MAN, and in hypothalamic nuclei. In both sexes, labeled cells in HVC, IMAN, RA, and nXII were larger than unlabeled cells. There were no sex differences in the size of either labeled or unlabeled cells in these song nuclei. The density of labeled cells per unit volume of tissue did not differ between the sexes in any song nucleus analyzed. However, because males have larger HVC and RA than females, males have a greater total number of hormone-sensitive cells in these regions than do females. Comparison of these results with measures of hormone accumulation in zebra finches and tropical duetting wrens suggests that the complexity of song that a bird can produce is correlated with the total number of hormone-sensitive cells in song nuclei. PMID- 1431850 TI - An antigen present in the Drosophila central nervous system only during embryonic and metamorphic stages. AB - We report here about an antigen that is expressed in the central nervous system (CNS) of Drosophila only during the embryonic and metamorphic stages. In Drosophila, axonogenesis and synaptogenesis occur twice during the development: first in the embryonic and second in the metamorphic stages. We generated monoclonal antibodies (MAbs) in order to obtain molecular probes for analyzing axonogenesis or synaptogenesis in the CNS on the assumption that good candidates for molecules responsible for such phenomena must be present in the neuropil during those stages exclusively. As a result, we found MAb 66B2 whose intense immunoreactivity in the neuropil of the CNS was observed exclusively in the embryo and pupa, and not in the larva and adult. Immunoblot analyses showed that MAb 66B2 binds specifically to a protein with an apparent molecular weight of 350 K and neutral pI in the prepupal CNS. A significant amount of the antigen was isolated in forms that were soluble without detergent. Results of immunohistochemistry with MAb 66B2 in a primary culture of embryos showed that some live cells in the ganglion-like cluster were stained, and that neuronal cell bodies and neurites emanating from there were negative. These results strongly suggest that the 66B2 antigen observed in the CNS is an extracellular matrix component secreted from nonneuronal cells. These developmental changes in the 66B2 immunoreactivity in the CNS presumably reflect dynamic changes of an extracellular matrix in the CNS that are accompanied by axonogenesis or synaptogenesis. PMID- 1431851 TI - Electric organ morphology of Sternopygus macrurus, a wave-type, weakly electric fish with a sexually dimorphic EOD. AB - In several species of electric fish with a sex difference in their pulse-type electric organ discharge (EOD), the action potential-generating cells of the electric organ (electrocytes) of males are larger and more invaginated compared to females. Androgen treatment of females and juveniles produces a longer duration EOD pulse that mimics the mature male EOD, with a concurrent increase in electrocyte size and/or membrane infolding. In Sternopygus macrurus, which generates a wave-type EOD, androgen also increases EOD pulse duration. To investigate possible morphological correlates of hormone-dependent changes in EOD in Sternopygus, we examined electric organs from both fish collected in the field, and untreated and androgen-treated specimens in the laboratory. The electrocytes are cigar shaped, with prominent papillae on the posterior, innervated end. Electrocytes of field-caught specimens were significantly larger in all parameters than were electrocytes of specimens maintained in the laboratory. EOD pulse duration and frequency were highly correlated, and were significantly different between the sexes in sexually mature fish. Nevertheless, no sex difference in electrocyte morphology was observed, nor did any parameters of electrocyte morphology correlate with EOD pulse duration or frequency. Further, whereas androgen treatment significantly lowered EOD frequency and broadened EOD pulse duration, there was no difference in electrocyte morphology between hormone-treated and control groups. Thus, in contrast to results from studies on both mormyrid and gymnotiform pulse fish, electrocyte morphology is not correlated with EOD waveform characteristics in the gymnotiform wave-type fish Sternopygus. The data, therefore, suggest that sex differences in EOD are dependent on changes in active electrical properties of electrocyte membranes. PMID- 1431852 TI - Wetland management strategies that enhance waterfowl habitats can also control mosquitoes. AB - Two studies in California wetlands and a third in Minnesota wetlands indicate that management practices designed to enhance habitat quality for waterfowl can concurrently reduce mosquito problems. In a seasonally flooded pickleweed wetland in Suisun Marsh, Solano Co., CA, we demonstrated that reducing plant-cover by 50% increased benthic densities of chironomid midge and dytiscid beetle larvae; these insects can be important in waterfowl diets. This manipulation also concentrated Aedes melanimon and Culiseta inornata mosquito larvae along wetland perimeters; thus, the need for control measures was greatly restricted spatially. A study in 9 experimental ponds in Suisun Marsh demonstrated that higher water levels could enhance populations of the macroinvertebrates important in waterfowl diets; general macroinvertebrate densities were higher at 60 cm depths than 20 cm or 40 cm depths. In contrast, Cs. inornata densities were lowest at 60 cm depths and highest at 20 cm depths. A study conducted in a perennial-water cattail wetland in Minneapolis-St. Paul, MN, demonstrated that a temporary water-level drawdown, designed to enhance waterfowl habitat quality of perennial-water wetlands, also reduced densities of Coquillettidia perturbans mosquito larvae. These mosquitoes disappeared immediately after the drawdown, but even after water depths were restored to pre-drawdown levels, significant numbers did not reappear until 4 years post-drawdown. Studies in 202 other Minnesota wetlands also demonstrated the susceptibility of Cq. perturbans populations to drawdown, but the impact of drawdown was greater in stands of emergent cattail than in floating cattail. PMID- 1431853 TI - Efficacy of Bacillus thuringiensis var. israelensis against larvae of the southern buffalo gnat, Cnephia pecuarum (Diptera: Simuliidae), and the influence of water temperature. AB - Susceptibility of southern buffalo gnat larvae to Bacillus thuringiensis var. israelensis (B.t.i.) was studied during 1986-88. Tests were conducted using Vectobac 12AS in a mini-gutter aquatic bioassay system. Mini-gutter tests using a 4.5 ppm B.t.i. concentration and a 10 min exposure period confirmed a positive correlation between water temperature and B.t.i. effectiveness. Significantly lower larval mortality occurred as water temperature decreased below 9 degrees C, indicating that proper timing of B.t.i. application is essential to maximize larval control. Even with this temperature limitation, larval control using B.t.i. should provide an economically effective means of preventing outbreaks of the southern buffalo gnat. PMID- 1431854 TI - Effect of per os Edhazardia aedis (Microsporida: Amblyosporidae) infection on Aedes aegypti mortality and body size. AB - Infection with Edhazardia aedis uninucleate spores had less effect on Aedes aegypti larval mortality and adult body size than did larval diet. Larval mortality averaged 60-81% in starved larvae and 2-16% in well-fed larvae. No significant amounts of larval mortality could consistently be attributed to exposure to the parasite at dosages of 1.5 x 10(3) or 1.5 x 10(5) spores/ml. Infection rates in adults surviving exposure to the parasites as larvae ranged from 30 to 59%. Infected adults had significantly smaller body sizes than uninfected adults or controls. Storage of spores in water reduced infectivity gradually over the course of 36 h. By 48 h, the spores were not able to infect mosquito larvae. Spore infectivity was eliminated by drying. PMID- 1431855 TI - Penetration of ultra-low volume applied insecticide into dwellings for dengue vector control. AB - Determinations on the penetration of ultra-low volume applied insecticide into dwellings was accomplished with a model house in Frederick, MD, USA, and native houses in Santo Domingo, Dominican Republic. Results from the model house tests show that aerosol droplets, with a volume median diameter of 4 microns, penetrated and remained suspended in low recesses of the building during the first 2 min after spraying. Similar results were found with tests in Santo Domingo, where man-made or natural obstructions were determined to be critical factors in aerosol penetration. PMID- 1431856 TI - Fate of Bacillus sphaericus and Bacillus thuringiensis serovar israelensis in the aquatic environment. AB - Bacillus sphaericus spores were suspended in bottles of filtered (0.45 microns) freshwater and seawater under various conditions of temperature, pH and salinity. Heat resistant culturable counts (spores) slowly decreased with time. Spores suspended in dialysis bags submerged in a freshwater pond or in flowing seawater underwent a more rapid drop in heat resistant spore counts than did spores held in bottles. Thus, laboratory studies may overestimate spore longevity in the environment. Spore settling rate was related to the nature of particulate material in the water column. Paraspores (or perhaps spores and toxin) of B. thuringiensis serovar israelensis (B.t.i.) had a greater tendency to adhere to and settle with suspended sediment and fine particulates than did paraspores of B. sphaericus. These observations may at least partially explain the greater persistence of B. sphaericus larvicidal activity in field tests than that of B.t.i.. PMID- 1431857 TI - Reduction of mortality rates of Bacillus thuringiensis var. israelensis aqueous suspensions due to freezing and thawing. AB - When studying the behavior (carry, dispersion, persistence) of Bacillus thuringiensis var. israelensis (B.t.i.) formulations used in the treatment of rivers or streams for black fly control, a large number of samples containing small quantities of B.t.i. are required for proper analysis. Freezing is a useful procedure to prevent enzymatic alteration or bacterial growth in samples before bioassays are to be performed. Using Aedes atropalpus neonate larvae, we studied the effect of freezing and thawing of B.t.i. aqueous suspensions by looking at mortality response parameters such as the slope and the LC50 of the probit regression. Initial concentration values of 1, 5, 10 and 20 mg/liter at the moment of freezing of the B.t.i. suspensions did not significantly affect toxicity. The number of freeze-thaw cycles greatly increased the LC50 values without much change to the slope of the log-probit regressions. We derived an equation that allowed us to compensate for the loss of toxicity of a given B.t.i. sample, knowing the number of freeze-thaw cycles. PMID- 1431858 TI - Blood-feeding of Culex mosquitoes in an urban environment. AB - The modified capillary tube precipitin test was used to identify blood meal sources of Culex quinquefasciatus emerging from sewage ditches in East Baton Rouge Parish, Louisiana. Canines were the primary hosts, but Passeriformes and humans were also suitable blood meal sources. The percentage of Cx. quinquefasciatus feeding on these 3 hosts fluctuated with the habitat and the season. PMID- 1431859 TI - Influence of moonlight on light trap catches of the malaria vector Anopheles nuneztovari in Venezuela. AB - A significant effect (P = 0.002) of moonlight on light trap catches of Anopheles nuneztovari females was observed during a longitudinal study in western Venezuela. The catch with no moon was 1.86 times larger than with full moon. Nevertheless, moonlight does not seem to have any effect on the composition of adult mosquito population since the difference in the parous rate of females collected during full moon and during no moon was not significant (P greater than 0.05). PMID- 1431860 TI - Distribution and control of Chironomus riparius (Diptera: Chironomidae) in a polluted creek. AB - Mass emergences of adult Chironomus riparius have been regularly occurring in late February near residential areas adjacent to a creek receiving municipal sewage effluent located in Lexington, Kentucky. Prior to attempting control of this chironomid, the larval distribution of this species in the creek was investigated. Although large numbers of larvae were being produced in this creek, the greatest larval density occurred downstream from an adjacent horse "muck" pile and an adjacent landfill. Application of Vectobac-6AS reduced larval density in these areas but Vectobac-G did not. PMID- 1431861 TI - An episode of resistance to permethrin in larvae of Simulium squamosum (Diptera: Simuliidae) from Cameroon, after 3 1/2 years of control. AB - Because of the biting nuisance from females of Simulium squamosum, a 30 km section of the Sanaga River (Cameroon) was treated since 1987 with permethrin for the control of larval populations. In 1990, resistance to permethrin occurred in a small proportion of the larvae, with a resulting 2-4x increase of the LC95 for dead larvae (moribund larvae considered as live). In 1991, after a 6-month interruption of the treatments, susceptibility to permethrin returned to the initial level, and was similar to the susceptibility of S. squamosum larvae from a non-treated section of the Sanaga. In the context of a small-scale control program, resistance to permethrin can be reversible, and it can be avoided by rotation with other types of insecticides such as Bacillus thuringiensis serovar, israelensis. PMID- 1431862 TI - New self-marking device for dispersal studies of black flies (Diptera: Simuliidae). AB - An effective and inexpensive device is described for marking newly emerged black flies with fluorescent dust. Survival of marked adults of Simulium venustum s.l. and Stegopterna mutata s.l. did not differ significantly from unmarked individuals over a 5-day period. Marked individuals were attracted to human hosts in landing biting tests, and the portions of the self-marking trap lying just above the water surface did not appear to significantly hamper black fly emergence success. PMID- 1431863 TI - Degradation of malathion in thermally generated aerosols. AB - The degradation of malathion, undiluted and diluted with No. 2 fuel oil, in thermally generated aerosol clouds was examined at selected temperatures ranging from 121 to 566 degrees C. Undiluted malathion residues decreased from 1.76 to 0.21 micrograms/ml over this range of temperatures. Malathion diluted with fuel oil decreased from 0.14 to 0.02 microgram/ml as the temperature was increased 288 to 510 degrees C. PMID- 1431864 TI - Variation in Aedes aegypti larval indices over a one year period in a neighborhood of Merida, Yucatan, Mexico. AB - Surveys for Aedes aegypti larvae were conducted to provide an estimate of the magnitude and timing of seasonal variations in larval indices in one colonia in Merida, Yucatan, Mexico, and to assess how the proportion of disposable and non disposable containers as larval production sites varies. Breteau indices exceeded 200 during the months of July and August, and disposable containers were important year-round larval production sites. PMID- 1431865 TI - Distributional records from the U.S. Air Force ovitrapping program--1991. AB - During 1991, ovitrapping was conducted by 37 U.S. Air Force installations. Sixteen installations were positive for Aedes albopictus. The number (449) and percent (21.5%) of Ae. albopictus-positive ovipaddles was almost 4 times that of the previous year. The collections of Ae. albopictus at Columbus Air Force Base (AFB), MS, and Shaw AFB, SC, are new records for Lowndes and Sumter counties, respectively. Nine installations were positive for Ae. aegypti; 21 were positive for Ae. triseriatus. PMID- 1431866 TI - Are cytokines pathogenic factors in the physiologic and metabolic sequelae of spinal cord injury? PMID- 1431867 TI - Clinical and pharmacokinetic aspects of high dose oral baclofen therapy. AB - Baclofen is a centrally acting muscle relaxant used for treatment of spasticity. Some patients, to experience adequate symptomatic relief, require dosages of baclofen that significantly exceed the conventional 80 mg daily maximum advocated by the 1992 Physicians' Desk Reference. In this pilot study of baclofen kinetics and dynamics in eleven patients, the safety and efficacy of high dose baclofen was confirmed. The data suggest that the pharmacokinetics of high dose baclofen may vary from those described previously. Time-to-peak plasma levels and plasma half-lives were noted to be substantially longer than prior reports indicate. Baclofen blood levels were observed to rise gradually over time in some patients on a stable dosing regimen, probably a result of impaired renal clearance. These findings may indicate that a change in pattern of prescription is warranted and that a reliable and practical measurement of systemic baclofen levels has a useful role in clinical practice, particularly for the patient with neurogenic bladder and potential renal insufficiency. PMID- 1431868 TI - Drug use and abuse in an urban veteran spinal cord injured population. AB - Substance abuse in the spinal cord injured (SCI) population has been addressed in a few controlled studies. These reports have led to the belief that many SCI patients were illicit drug users prior to their injury and that their drug abuse was a contributing cause of their accidents. One large study determined from answers obtained on a questionnaire that drug abuse, other than alcohol, was prevalent among injured veterans. Our study uses urine toxicology to determine the frequency of drug use and abuse, excluding alcohol, in 72 inpatients and 81 outpatients associated with an urban Veterans Affairs Medical Center. In a blinded experiment, urinary concentrations of opiates, barbiturates, amphetamines, methadone, benzodiazepines, and cocaine were determined with Syva reagents on an Abbott VP. Urinary cannabinoids were determined using Abbott TDX and the FPIA method. The use of illicit (unprescribed) drugs was surprisingly low (< or = 13 percent) for an urban medical center. Outpatient cannabinoid abuse was significantly more frequent than inpatient usage (p < 0.01). Barbiturates were not found in any patient. Benzodiazepines were taken most commonly (29 percent). Since benzodiazepine usage is the direct result of physician prescription, wide spread usage of this agent is avoidable. Physicians should pay attention to the probable deleterious consequences of benzodiazepine addiction related to depressive effects on the central nervous system caused by its chronic use. PMID- 1431869 TI - Bipolar latissimus dorsi transposition and functional neuromuscular stimulation to restore elbow flexion in an individual with C4 quadriplegia and C5 denervation. AB - A bipolar latissimus dorsi transposition was performed on a 17-year-old male patient with a C4 spinal cord injury and complete peripheral denervation at C5. Electrical stimulation of the paralyzed but excitable latissimus dorsi provided elbow flexion that could not be achieved with the paralyzed and denervated elbow flexors. The muscle was attached from the coracoid to the ulna allowing the elbow to be flexed with the forearm and wrist maintained in the neutral position. Following a 6-week immobilization period, the transposed muscle was exercised daily with intramuscular stimulation to increase both strength and endurance. By the fourth month after surgery, the subject could control elbow flexion proportionally with contralateral shoulder elevation using a shoulder position transducer. Functionally, the subject was able to use the neuroprosthetic system to bring his hand to his mouth and feed himself with the aid of a universal cuff and a support to stabilize the shoulder. PMID- 1431870 TI - Heterotopic ossification of the extensor tendons in the hand associated with traumatic spinal cord injury. AB - Heterotopic ossification (HO) occurs in spinal cord injury (SCI), most frequently in the large joints such as hips, shoulders, knees, and elbows. It always occurs below the level of neurologic lesion. In the upper extremities, HO associated with SCI usually involves the flexor side of the involved joint. HO has only been reported once to involve the hands and rarely develops parallel to the long bones. We present a 44-year-old male with C5 traumatic SCI who developed HO involving the extensor tendons of one hand. The HO was discovered four months after the SCI and involved the extensor sheaths of the second, third, and fourth digits, from the metacarpal-phalangeal joint to the proximal inter-phalangeal joint. The patient had been improving neurologically with poor to fair extension of the right wrist allowing for tenodesis finger flexion, but with the onset of HO he lost some functional grasp. Diagnosis, possible etiology, and treatment (including options of radiation therapy and surgery) are discussed. PMID- 1431871 TI - Osteoporosis in spinal cord injury: using an index of mobility and its relationship to bone density. AB - This study was undertaken to improve quantification of the extent of osteoporosis that accompanies spinal cord injuries (SCI) of various types, using single photon densitometry. In this study, we evaluated subjects with complete and incomplete SCI to determine whether there is a correlation between mobility and bone density. We created an index to rank the various levels of mobility among SCI subjects. Mobility index parameters ranged from 1, for complete immobility, to 9, for the full mobility of the uninjured control population. Incomplete SCI subjects (motor and/or sensory) ranked from 2 to 8 on the mobility scale. We also attempted to define clearly the mechanism of osteoporosis in those with predominantly unilateral SCI (Brown-Sequard syndrome). Using single photon absorptiometry (SPA), we found a strong correlation between our mobility index and observed bone density. These observations clearly show that osteoporosis is affected by the subject's level of physical activity. These observations also support the hypothesis that SCI individuals benefit from efforts to maintain a standing posture with some regularity. This effort to improve bone density slows the development of osteoporosis, a process that results in physical impairments in the SCI population. PMID- 1431872 TI - Care and treatment of spinal cord injury patients. PMID- 1431873 TI - Uptake of selenotrisulfides of glutathione and cysteine by brush border membranes from rat intestines. AB - The uptake of selenodiglutathione and selenodicysteine was compared to that of selenite by brush border membrane vesicles (BBMV) prepared from rat intestinal tracts. It was found that it is critical to maintain a pH of 6.0 or below to prevent the spontaneous breakdown of these compounds. When conducted at pH 6.0, the uptake of selenodiglutathione and selenodicysteine was more than ten times faster than for selenite selenium. Ligated intestinal loop studies were conducted to determine if similar results would be obtained in vivo. In comparison to selenite, selenium absorption was enhanced 68% and the transfer to the body increased 2.4-fold when selenium as selenodiglutathione was placed in the ileum. The absorption of selenium as selenodicysteine was increased by 57% and the transfer doubled in comparison to selenite when placed in the ileum. Thus, the stimulated absorption of selenite by glutathione or cysteine appears to be through the formation of complexes with these compounds. PMID- 1431874 TI - Cytotoxic activity of platinum (II) complexes with tri-n-butylphosphine. Crystal structure of the dinuclear hydrazine-bridged complex, cis,cis-[PtCl(PBu3n)2(mu N2H4)PtCl(PBu3n) 2] (ClO4)2.2CHCl3. AB - A series of platinum(II) tri-n-butylphosphine complexes having the formulas cis [PtCl2L2], NEt4[PtCl3L], [PtCl(en)L]Cl, [Pt(en)L2](ClO4)2, sym-trans-[Pt2Cl4L2], [Pt2Cl2L4](ClO4)2, trans,trans-[PtCl2L(mu-N2H4)PtCl2L] trans,trans-[PtCl2L(mu en)PtCl2L], and cis,cis-[PtClL2(mu-N2H4)PtClL2](ClO4)2 (L = tri-n-butylphosphine; en = ethylenediamine) have been synthesized and their cytotoxic activity in vitro and in vivo has been studied. The solution behavior of the novel dinuclear diamine-bridged platinum(II) complexes has been investigated by means of UV and 31P NMR spectroscopy. For the ionic hydrazine compound cis,cis-[PtClL2(mu N2H4)PtClL2](ClO4)2, an x-ray structure determination is reported. Crystal data: space group P2(1)/a, a = 17.803(1), b = 18.888(3), c = 12.506(3) A, beta = 107.97(2) degrees, Z = 2, R = 0.052, RW = 0.058. The platinum coordination is approximately square-planar, with the bond lengths Pt-Cl = 2.358(5), Pt-N = 2.15(1), Pt-P(trans to Cl) = 2.260(5), and Pt-P(trans to N) = 2.262(6) A. All investigated compounds were cytotoxic in vitro against L1210 cells and showed no cross-resistance to cisplatin. On the other hand, no antitumor activity was observed vs L1210 leucemia in DBA2 mice. PMID- 1431875 TI - Synthesis, characterization, and antiinflammatory activity of naproxen complexes with rare earth (III). AB - RE(III) complexes of Naproxen(HNap) have been synthesized and characterized by elemental analyses, conductance measurements, solubilities, thermal analysis, infrared, proton magnetic resonance, and electronic spectral data. The elemental analyses reveal the presence of 1:3 (metal:ligand) stoichiometry and the IR spectra suggest the carboxylate group of HNap functions, as a bridging ligand to coordinate to RE(III) ions. The electronic spectra recorded in solid exhibit only slight shifts in visible regions, on which beta, delta and b1/2 of covalent parameters have been calculated. Formalin-induced rat paw edema and croton oil induced rat ear edema inflammatory models were chosen to examine the antiinflammatory activity of Nd(III) complex, which ascertained enhanced antiinflammatory activity relative to the ligand. PMID- 1431876 TI - Synthesis and biological studies of new lipid-soluble cisplatin analogues entrapped in liposomes. AB - A series of highly lipophilic platinum(II) complexes of the type cis [(RNH2)2PtX2] have been synthesized, where R = ethyl, propyl, isopropyl, butyl, cyclopropyl, cyclopentyl, or neopentyl and X = either long-chain carboxylate, such as decanoate (C10), laurate (C12), myristate (C14), heptadecanoate (C17), stearate (C18), nonadecanoate (C19), or 2,2,3,3 tetramethylcyclopropylcarboxylate, or branched-chain carboxylate, such as neopentanoate, neohexanoate, neoheptanoate, neononanoate, or neodecanoate. These complexes have been characterized by elemental analysis, IR, and 13C and 195Pt NMR spectroscopic techniques. The platinum complexes were entrapped in multilamellar vesicles composed of dimyristoyl phosphatidylcholine (DMPC) and dimyristoyl phosphatidylglycerol (DMPG) at a 7:3 molar ratio and tested for antitumor activity. The entrapment efficiency of liposomal platinum (L-Pt) complexes ranged from 60 to 100%. The percentage of T/C obtained after a single i.p. injection of the optimal dose of L-Pt complexes tested against L1210 leukemia ranged from 90 to 125%. These L-Pt preparations did not show significant antitumor activity in mice. PMID- 1431877 TI - New perspectives on the structure and function of transferrins. AB - Structure-function relationships for transferrins are discussed in the light of recent X-ray crystal structure determinations. A common folding pattern into two lobes, each comprising two domains is adopted; this allows the tight, but reversible binding of iron. Uptake and release of iron involve substantial domain movements which open and close the binding clefts. The iron binding sites are similar and the key role of the CO3(2-) anion bound with each Fe3+ can now be understood; structural differences near the iron binding sites suggest reasons for the different binding properties of serum transferrin and lactoferrin. The glycan moieties do not appear to affect the protein structure or metal binding properties; they are not clearly seen in the X-ray analyses but have been modelled. The accommodation of different metals and anions is illustrated by the crystal structures of Cu2+ and oxalate-substituted lactoferrins; Al3+ binding is of particular interest. New results on transferrin-receptor interactions with transferrin, and melanotransferrin and an invertebrate transferrin (both of which have defective C-terminal binding sites), emphasize possible functional differences between the two lobes. The availability of site-specific mutants of both transferrin and lactoferrin now offers the opportunity to probe the structural determinants of iron binding, iron release, and receptor binding. PMID- 1431878 TI - Structure, function, and evolution of ferritins. AB - The ferritins of animals and plants and the bacterioferritins (BFRs) have a common iron-storage function in spite of differences in cytological location and biosynthetic regulation. The plant ferritins and BFRs are more similar to the H chains of mammals than to mammalian L chains, with respect to primary structure and conservation of ferroxidase center residues. Hence they probably arose from a common H-type ancestor. The recent discovery in E. coli of a second type of iron storage protein (FTN) resembling ferritin H chains raises the question of what the relative roles of these two proteins are in this organism. Mammalian L ferritins lack ferroxidase centers and form a distinct group. Comparison of the three-dimensional structures of mammalian and invertebrate ferritins, as well as computer modeling of plant ferritins and of BFR, indicate a well conserved molecular framework. The characterisation of numerous ferritin homopolymer variants has allowed the identification of some of the residues involved in iron uptake and an investigation of some of the functional differences between mammalian H and L chains. PMID- 1431879 TI - Haem binding to ferritin and possible mechanisms of physiological iron uptake and release by ferritin. AB - Haem binding to horse spleen ferritin and Pseudomonas aeruginosa bacterioferritin has been studied by spectroscopic methods. A maximum of 16 haems per ferritin molecule, and 24 haems per bacterioferritin molecule, has been shown to bind. The influence of the bound haem on the rate of reductive iron release has been investigated. With a range of reductants and in the absence of haem the rate of release varied with the reductant, but in the presence of haem the rate was both independent of the reductant and faster than with any of the reductants alone. This indicates the rate-limiting step for iron release in the absence of haem was electron-transfer across the protein shell. Based on the results obtained with the in vitro assay system and from a consideration of data currently in the literature, plausible schemes for ferritin and bacterioferritin iron uptake and release are described. PMID- 1431880 TI - Coordination of cellular iron metabolism by post-transcriptional gene regulation. AB - Maintenance of cellular iron homeostasis demands the coordination of iron uptake, intracellular storage, and utilization. Recent investigations suggest that a single genetic regulatory system orchestrates the expression of proteins with central importance for all three aspects of cellular iron metabolism at the level of mRNA stability and translation. Two components of this regulatory system have been defined: a cis-acting mRNA sequence/structure motif called "iron-responsive element" (IRE) and a specific trans-acting cytoplasmic binding protein, here referred to as "IRE-binding protein" (IRE-BP). As an early event in the regulatory cascade, cellular iron deprivation induces the IRE-binding activity of IRE-BP, whereas binding activity is reduced in iron-replete cells. IRE-BP is highly homologous to the iron-sulphur (Fe-S) protein aconitase which strongly suggests that IRE-BP is an Fe-S protein itself. Control over IRE-BP activity by the cellular iron status is exerted post-translationally and likely involves changes between (4Fe-4S) and (3Fe-4S) states of the postulated IRE-BP Fe-S cluster. In addition, post-translational regulation of IRE-BP activity via heme has been proposed. Subsequent to its activation, IRE-BP binds with high affinity to single IREs contained in the 5' untranslated regions (UTRs) of ferritin and erythroid 5-aminolevulinic acid synthase (eALAS) mRNAs. The binding represses translation of these proteins involved in iron storage and utilization, respectively. In contrast, iron uptake is largely regulated via multiple IREs in the 3' UTR of transferrin receptor (TfR) mRNA. TfR-IREs are required for the iron sensitive control of TfR mRNA stability. IRE-BP binding stabilizes TfR gene transcripts against as yet undefined ribonucleases. As a result of these regulatory interactions, iron starvation induces the expression of TfR, thereby increasing iron uptake, and represses the synthesis of proteins involved in iron storage and utilization. As cellular iron levels rise, the homeostatic balance is maintained by lowering iron uptake and increasing iron storage in ferritin. PMID- 1431881 TI - Structural requirements for high efficiency endocytosis of the human transferrin receptor. AB - Wild-type and mutant human transferrin receptors (TR) have been expressed in chicken embryo fibroblasts using a helper-independent retroviral vector. By functional studies of the mutant TRs, we have identified the tetrapeptide sequence, YXRF, in the cytoplasmic tail of the receptor as the internalization signal required for high efficiency endocytosis and shown that transplanted internalization signals from the low density lipoprotein receptor (LDLR) and the cation-independent mannose-6-phosphate receptor (Man-6-PR) are able to promote rapid internalization of the human TR. A six-residue LDLR signal, FDNPVY, is required for activity in TR, whereas a four-residue Man-6-PR signal, YSKV, is sufficient. These data indicate that internalization signals are interchangeable self-determined structural motifs and that signals from type I membrane proteins are active in a type II receptor. Putative internalization signals in the cytoplasmic tails of other receptors and membrane proteins can be identified based on the sequence patterns of the LDLR, Man-6-PR, and TR signals. Two such putative four-residue internalization signals, one from the poly-Ig receptor and one from the asialoglycoprotein receptor, were tested for activity by transplantation into TR and were found to promote high efficiency internalization. These results suggest that an exposed tight turn is the conformational motif for high efficiency endocytosis. PMID- 1431883 TI - Iron-mediated DNA damage: sensitive detection of DNA strand breakage catalyzed by iron. AB - Oxidative DNA damage is involved in mutagenesis, carcinogenesis, aging, radiation effects, and the action of several anticancer drugs. Accumulated evidence indicates that iron may play an important role in those processes. We studied the in vitro effect of low concentrations of Fe(II) alone or Fe(III) in the presence of reducing agents on supercoiled plasmid DNA. The assay, based on the relaxation and linearization of supercoiled DNA, is simple yet sensitive and quantitative. Iron mediated the production of single and double strand breaks in supercoiled DNA. Iron chelators, free radical scavengers, and enzymes of the oxygen reduction pathways modulated the DNA damage. Fe(III)-nitrilotriacetate (NTA) plus either H2O2, L-ascorbate, or L-cysteine produced single and double strand breaks as a function of reductant concentration. A combination of 0.1 microM Fe(III)-NTA and 100 microM L-ascorbate induced detectable DNA strand breaks after 30 min at 24 degrees C. Whereas superoxide dismutase was inhibitory only in systems containing H2O2 as reductant, catalase inhibited DNA breakage in all the iron-mediated systems studied. The effect of scavengers and enzymes indicates that H2O2 and .OH are involved in the DNA damaging process. These reactions may account for the toxicity and carcinogenicity associated with iron overload. PMID- 1431882 TI - Ferritin synthesis on polyribosomes attached to the endoplasmic reticulum. AB - The evidence that ferritin is synthesized both on free polyribosomes and on polyribosomes attached to the endoplasmic reticulum is reviewed. Evidence that some ferritin is secreted from cells after synthesis on bound polyribosomes was found to be inconclusive. PMID- 1431885 TI - Brain iron homeostasis. AB - The anatomical and cellular distribution of non-haem iron, ferritin, transferrin, and the transferrin receptor have been studied in postmortem human brain and these studies, together with data on the uptake and transport of labeled iron, by the rat brain, have been used to elucidate the role of iron and other metal ions in certain neurological disorders. High levels of non-haem iron, mainly in the form of ferritin, are found in the extrapyramidal system, associated predominantly with glial cells. In contrast to non-haem iron, the density of transferrin receptors is highest in cortical and brainstem structures and appears to relate to the iron requirement of neurones for mitochondrial respiratory activity. Transferrin is synthesized within the brain by oligodendrocytes and the choroid plexus, and is present in neurones, consistent with receptor mediated uptake. The uptake of iron into the brain appears to be by a two-stage process involving initial deposition of iron in the brain capillary endothelium by serum transferrin, and subsequent transfer of iron to brain-derived transferrin and transport within the brain to sites with a high transferrin receptor density. A second, as yet unidentified mechanism, may be involved in the transfer of iron from neurones possessing transferrin receptors to sites of storage in glial cells in the extrapyramidal system. The distribution of iron and the transferrin receptor may be of relevance to iron-induced free radical formation and selective neuronal vulnerability in neurodegenerative disorders. PMID- 1431884 TI - Ferric iron reduction and iron assimilation in Saccharomyces cerevisiae. AB - We have used the yeast Saccharomyces cerevisiae as a model organism to study the role of ferric iron reduction in eucaryotic iron uptake. S. cerevisiae is able to utilize ferric chelates as an iron source by reducing the ferric iron to the ferrous form, which is subsequently internalized by the cells. A gene (FRE1) was identified which encodes a protein required for both ferric iron reduction and efficient ferric iron assimilation, thus linking these two activities. The predicted FRE1 protein appears to be a membrane protein and shows homology to the beta-subunit of the human respiratory burst oxidase. These data suggest that FRE1 is a structural component of the ferric reductase. Subcellular fractionation studies showed that the ferric reductase activity of isolated plasma membranes did not reflect the activity of the intact cells, implying that cellular integrity was necessary for function of the major S. cerevisiae ferric reductase. An NADPH-dependent plasma membrane ferric reductase was partially purified from plasma membranes. Preliminary evidence suggests that the cell surface ferric reductase may, in addition to mediating cellular iron uptake, help modulate the intracellular redox potential of the yeast cell. PMID- 1431887 TI - The interactions of zinc, nickel, and cadmium with Xenopus transcription factor IIIA, assessed by equilibrium dialysis. AB - Transcription factor IIIA (TFIIIA) was isolated from Xenopus ovary and treated with 1,10-phenanthroline to remove zinc. The interactions of apoTFIIIA with Zn2+, Ni2+, and Cd2+ were studied by equilibrium dialysis under anaerobic conditions (pH 7.0, 25 degrees C), using 65ZnCl2, 63NiCl2, and 109CdCl2 as the radioligands. The data for binding of Zn2+, Ni2+, and Cd2+ to apoTFIIIA were best-fitted by a model with two classes of binding sites. For Zn2+, the apparent dissociation constants (KdlZn and Kd2Zn) for the high- and low-affinity sites were 1.0 x 10( 8) and 2.6 x 10(-5) M; the apparent binding capacities of the two classes were 0.8 +/- 0.5 and 9.6 +/- 0.3 g-atoms of Zn/mol; the Hill coefficient was 1.18, consistent with positive cooperativity of Zn-binding sites. For Ni2+, the apparent KdlNi and Kd2Ni values were 2.3 x 10(-5) and 5.2 x 10(-4) M; the apparent binding capacities were 2.3 +/- 0.6 and 8.6 +/- 0.6 g-atoms of Ni/mol; the Hill coefficient was 1.20, consistent with positive cooperativity of Ni binding sites. For Cd2+, the apparent KdlCd and Kd2Cd values were 2.8 x 10(-6) and 1.6 x 10(-4) M; the apparent binding capacities were 0.9 +/- 0.3 and 2.4 +/- 0.5 g-atoms of Cd/mol; the Hill coefficient was 0.53, consistent with negative cooperativity or heterogeneity of Cd-binding sites. This study has the following significance: First, it helps to resolve a controversy about the zinc content of purified TFIIIA. Second, it shows that the KdlZn of apoTFIIIA is less than the reported KdZn of thionein, consistent with the hypothesis that thionein modulates gene expression by competing with TFIIIA and other Zn-finger proteins for intracellular Zn2+ stores. Third, it confirms previous indirect evidence that the affinity of apoTFIIIA for Zn2+ is much greater than for Cd2+, and that the affinity for Cd2+ is greater than for Ni2+. PMID- 1431886 TI - The antimalarial effect of iron chelators: studies in animal models and in humans with mild falciparum malaria. AB - In this study we explore the antimalarial effects of 3-hydroxypyridin-4-ones (CP compounds), a family of bidentate orally effective iron chelators in experimental animal systems in vivo and in vitro, and examine whether the iron chelator deferoxamine (DF) is active against human infection with P. falciparum. There was direct relation between lipid solubility of the CP compounds, which would facilitate membrane transit, and their in vivo antimalarial action, suggesting direct intracellular iron chelation as the most likely explantation for the antimalarial effect of iron chelators. Results of the double-blind, placebo controlled trial of DF in humans with asymptomatic parasitemia provided unequivocal evidence that this iron-chelating agent has antimalarial activity. Depriving the parasite of a metabolically important source of iron may represent a novel approach to antimalarial drug development. DF is a relatively ineffective intraerythrocytic chelator, and our data indicate that other orally effective iron chelators may have superior antimalarial activity in vivo. A systematic screening of available iron chelating drugs may result in the identification of potentially useful antimalarial compounds. PMID- 1431888 TI - Conversion in the peptides coating cadmium:sulfide crystallites in Candida glabrata. AB - Cultures of Candida glabrata treated with CdCl2 form intracellular Cd(II) complexes that evolve with the time of culturing. Initially, glutathione (gamma ECG) appears to be the major buffering component. One type of Cd(II)-glutathione complex exists as a cadmium:sulfide (CdS) crystallite coated with glutathione. A time dependent change in the coating of the CdS particles occurs with a decrease in the (gamma ECG) content and a corresponding increase in the abundance of (gamma EC)nG peptides with (gamma EC)2G becoming the predominant peptide. The des Gly variant (gamma EC)2 appears in significant concentration only in late cultures. The evolution in isopeptide coating appears to be dependent on the sulfide content of the CdS particles. Cellular conditions that enhance the generation of sulfide ions facilitate the conversion from gamma ECG to (gamma EC)2G. PMID- 1431890 TI - Stimulatory effects of exogenous thyroid hormone and growth hormone on sn glycerol-3-phosphate dehydrogenase activity in the genetic-hypothyroid mutant mouse cerebellum: restricted to the second 20 days of postnatal life. AB - We recently reported that by postnatal day 40 the activity of sn-glycerol-3 phosphate dehydrogenase (GPDH) was significantly depressed in the cerebellum of genetic-hypothyroid mutant mice. This mutant mouse-GPDH combination was used in the present study to define the critical time period during which thyroid hormone (T4) and growth hormone (GH) are essential for maturation of Bergmann glial cells. Our findings are that (a) induction of GPDH activity in the Bergmann glial cell is dependent on T4, (b) T4 is most effective when administered during the second 20 days of postnatal life, (c) the effect of GH on GPDH activity is complementary to or synergistic with that of T4, and (d) Bergmann glial cells and radial glial fibers of the mutant mice contain immunoreactive GPDH following various hormonal treatments. These results suggest that T4 is indispensable for the maturation of Bergmann glial cells. PMID- 1431889 TI - K-252 compounds: modulators of neurotrophin signal transduction. AB - K-252 compounds, which share a common polyaromatic aglycon structure, are rather general and potent inhibitors of various protein kinases, including protein kinase C and tyrosine-specific protein kinases, and possibly act by interfering at or near the ATP binding site. However, chemical modifications in their sugar moiety can result in high specificity of the inhibitory action and, furthermore, can induce other stimulatory and inhibitory effects on nerve cells. These compounds are of particular interest because, in intact cells, they inhibit the actions of NGF and other neurotrophins without diminishing comparable actions of other growth factors. This effect seems to reflect a direct inhibitory action on trk neurotrophin receptor proteins. At concentrations lower than those necessary to inhibit neurotrophin actions, K-252a and K-252b have been shown to potentiate the stimulatory effects of NT-3 on different neurons in culture and on PC12 cells. The structural requirements for this effect seem to be different from those for the inhibition of neurotrophin actions. These findings raise the possibility of development of compounds of high selectivity, able to inhibit or potentiate the transduction mechanisms of individual neurotrophins, and identify K-252a and K-252b as lead compounds for the development of such selective molecules. Specific inhibitors and stimulators of neurotrophins would be valuable tools to investigate biological functions of the neurotrophins in vitro and in vivo. Furthermore, it is possible that, in the future, highly selective drugs with agonistic or antagonistic actions on neurotrophin mechanisms could become therapeutically useful in the treatment of neurological disease and injury. PMID- 1431891 TI - Distribution of free methylarginines in rat tissues and in the bovine brain. AB - A sensitive and specific method for determining three forms of methylarginine, i.e., NG-monomethylarginine, NG,NG-dimethylarginine, and NG,N'G-dimethylarginine, in mammalian tissues was developed. After partial purification by ion-exchange chromatography, the methylarginines were derivatized to phenylthiocarbamyl compounds and quantitatively determined using HPLC with a reverse-phase C18 column. In rat organs, the highest concentrations of methylarginines were observed in the spleen. In rat brain, cerebellum and olfactory bulb contained large amounts of NG-monomethylarginine and NG,NG-dimethylarginine. A detailed study of the distribution of methylarginines in the bovine brain was also made, and the concentration of NG,N'G-dimethylarginine was almost the same in all regions. The cerebellar gray matter, hippocampus, and hypothalamus contained large amounts of methylarginines. The distribution of methylarginines seems to parallel the distribution of nitric oxide synthase, which is known to be inhibited by NG-monomethylarginine. This may indicate that methylarginines play some role in controlling nitric oxide synthase activity. PMID- 1431892 TI - A casein kinase-like kinase phosphorylates beta-tubulin and may be a microtubule associated protein. AB - The hypothesis that casein kinase II (CKII) is a microtubule-associated protein kinase was investigated using a neuronal cell line and bovine brain. Heparin, an inhibitor of CKII, inhibited the phosphorylation of a PC12 cytosolic protein whose molecular weight was similar to that of beta-tubulin. Partially purified PC12 CKII was immunoreactive to an antibody directed against bovine CKII and was able to phosphorylate purified beta-tubulin in a heparin-inhibitable manner when the concentration of tubulin was less than 50 micrograms/ml. To better determine if CKII is a microtubule-associated protein kinase, bovine brain tubulin was chromatographed on FPLC Mono Q and phosphocellulose columns. Several tubulin casein kinase (TCK) activities were apparent. All TCK activities phosphorylated tubulin and casein, but none was able to phosphorylate the CKII-specific synthetic peptide RRREEETEEE. One of these TCK fractions was immunoreactive to the antibody directed against CKII, and this antibody labeled a 50-kDa molecular mass band that had a molecular mass distinctly different from those of the subunits of CKII. Thus, we suggest that a CKII-like protein, but not CKII, might be a microtubule-associated protein. PMID- 1431894 TI - Relationship between platelet monoamine oxidase B activity and alleles at the MAOB locus. AB - Genetic variations in monoamine oxidase (MAO)-B activity have been proposed to have a contributory role in several neurologic and psychiatric diseases. Variations in activity could affect rates of degradation of exogenous amines, including toxins, precursors of toxins (like 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine), or false transmitters, and of endogenous amines, such as neurotransmitters. In this study a highly polymorphic (GT)n repeat element was used to mark alleles at the MAOB locus. The MAOB allele status and levels of platelet MAO-B activity were determined for 41 control males. No correlation was noted between specific alleles and levels of MAO-B activity in this sample set. This suggests that the structural gene for MAOB is not usually the primary determinant of activity levels in platelets. PMID- 1431893 TI - Inhibition of phosphorylation of synapsin I and other synaptosomal proteins by beta-bungarotoxin, a phospholipase A2 neurotoxin. AB - Some snake venom neurotoxins, such as beta-bungarotoxin (beta-BuTX), which possess relatively low phospholipase A2 (PLA2) activity, act presynaptically to alter acetylcholine (ACh) release both in the periphery and in the CNS. In investigating the mechanism of this action, we found that beta-BuTX (5 and 15 nM) inhibited phosphorylation, in both resting and depolarized synaptosomes, of a wide range of proteins, including synapsin I. Naja naja atra PLA2, which has higher PLA2 activity, also inhibited phosphorylation but was less potent than beta-BuTX. At 1 nM, beta-BuTX and N. n. atra PLA2 inhibited phosphorylation of synapsin I only in depolarized synaptosomes. Synaptosomal ATP levels were not affected by 5 or 15 nM beta-BuTX or by 5 nM N. n. atra PLA2. Limited proteolysis, using Staphylococcus aureus V-8 protease, indicated that beta-BuTX inhibited phosphorylation of synapsin I in both the head and the tail regions. The inhibition of phosphorylation was not antagonized by nordihydroguaiaretic acid or indomethacin, suggesting that arachidonic acid derivatives do not mediate this inhibition. Furthermore, inhibition of phosphorylation by beta-BuTX and N. n. atra PLA2 was not altered in the presence of the phosphatase inhibitor okadaic acid, suggesting that stimulation of phosphatase activity is not responsible for this inhibition. Inhibition of protein phosphorylation by PLA2 neurotoxins and enzymes may be associated with an inhibition of ACh release. PMID- 1431895 TI - Nicotinylalanine increases the formation of kynurenic acid in the brain and antagonizes convulsions. AB - Kynurenic acid (KYNA) was quantified in the extracellular spaces of the rat hippocampus using microdialysis and HPLC (fluorimetric detection) to study the possible role of this tryptophan metabolite in the modulation of the function of the N-methyl-D-aspartate (NMDA) receptor. Addition of probenecid (1 mM), which is an inhibitor of the organic acid transport system, to the Ringer's solution perfusing the dialysis probe increased the KYNA concentration in the dialysate from 10.4 +/- 0.9 to 48 +/- 6 nM. Addition of 2 mM aminooxyacetic acid, a nonspecific inhibitor of KYNA synthesis, reduced this concentration by 50%. These data suggest that KYNA is continuously synthesized in the rat hippocampus. Nicotinylalanine (NAL), 200-400 mg/kg i.p., an analogue of kynurenine that is able to direct the flow of tryptophan metabolites toward the synthesis of KYNA, significantly increased the KYNA concentration in the hippocampal dialysate and significantly potentiated the effect of tryptophan on the accumulation of KYNA in the brain and other organs. This increase resulted in pharmacological actions compatible with an antagonism of the NMDA receptors. In fact, NAL antagonized sound-induced seizures and prevented death in DBA/2 mice. Pretreatment of the mice with D-serine (100 micrograms intracerebroventricularly), a glycine agonist and a competitive antagonist of KYNA, completely prevented the anticonvulsive action of NAL. These data suggest that changes in the extracellular concentration of KYNA in the brain are associated with a modulation of NMDA receptor function. PMID- 1431896 TI - Stimulation of phosphatidylinositol hydrolysis by brain-derived neurotrophic factor and neurotrophin-3 in rat cerebral cortical neurons developing in culture. AB - Phosphatidylinositol (PI) breakdown represents a powerful system participating in the transduction mechanism of some neurotransmitters and growth factors and producing two second messengers, diacylglycerol and inositol trisphosphate. The transformation of PC12 neuroblastoma cells into neuron-like cells induced by nerve growth factor (NGF) is preceded by a rapid stimulation of PI breakdown; however, it was not known whether PI breakdown mediates actions of other members of the neurotrophin family. The present study analyzed the effects of NGF, brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) on PI breakdown in primary cultures of embryonic rat brain cells. Cultures were grown for 7 days; PI was then labeled by incubating cultures with myo-[3H]inositol, which then were exposed acutely to growth factors. BDNF and NT-3, but not NGF, elevated the levels of labeled inositol phosphates within 10-15 min after addition to the cultures in a dose-dependent manner. ED50 values for BDNF and NT-3 were 12.4 and 64.5 ng/ml, respectively. Comparable effects were found in cultures of cortical, striatal, and septal cells. The actions of BDNF and NT-3 probably reflect actions on neurons, because no effects were seen in cultures of nonneuronal cells. In contrast, basic fibroblast growth factor induced a marked stimulation of PI breakdown in cultures of nonneuronal cells. K252b, which selectively blocks neurotrophin actions by inhibiting trk-type receptor proteins, prevented the PI breakdown mediated by BDNF and NT-3. The findings suggest that rapid and specific induction of PI breakdown is involved in the signal transduction of BDNF and NT 3, and they provide evidence that cortical neurons are functionally responsive to BDNF and NT-3 during development. PMID- 1431897 TI - Nicotinic agonists, phorbol esters, and growth factors activate two extracellular signal-regulated kinases, ERK1 and ERK2, in bovine chromaffin cells. AB - Treatment of bovine chromaffin cells with nicotinic agonists, phorbol esters, and growth factors increases protein kinase activity toward microtubule-associated protein-2 and myelin basic protein (MBP) in vitro. To characterize the kinases that are activated by these agents, we separated chromaffin cell proteins by electrophoresis in sodium dodecyl sulfate-polyacrylamide gels into which MBP had been incorporated, allowed the proteins to renature, and then assayed MBP kinase activity by incubating the gels with [gamma-32P]ATP. Chromaffin cells contain a family of kinases that phosphorylate MBP in vitro. Two of these kinases, of M(r) 46,000 and 42,000 (PK46 and PK42), were activated by treatment of the cells with dimethylphenylpiperazinium (DMPP), phorbol 12,13-dibutyrate (PDBu), or insulin like growth factor I (IGF-I). Activation of PK46 and PK42 by DMPP was dependent on extracellular Ca2+, whereas the effects of PDBu and IGF-I were Ca2+ independent. Down-regulation of protein kinase C by incubation of the cells with PDBu abolished the activation of PK46 and PK42 by DMPP, PDBu, and IGF-I. Staurosporine, a protein kinase C inhibitor, prevented the activation of PK46 and PK42 by DMPP and PDBu but did not block the activation of these kinases by IGF-I. Immunoblotting experiments with antiphosphotyrosine (anti-PTyr) antibodies demonstrated that agents that increased the kinase activities of PK46 and PK42 also increased the apparent PTyr content of M(r) 46,000 and 42,000 proteins. PK46 and PK42 comigrated with proteins that reacted with antibodies against extracellular signal-regulated kinases (ERKs). Thus, PK46 and PK42 appear to be the bovine homologues of ERK1 and ERK2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431898 TI - Extracellular brain glucose levels reflect local neuronal activity: a microdialysis study in awake, freely moving rats. AB - The relationship between brain extracellular glucose levels and neuronal activity was evaluated using microdialysis in awake, freely moving rats. The sodium channel blocker tetrodotoxin and the depolarizing agent veratridine were administered through the dialysis probe to provoke local changes in neuronal activity. The extracellular glucose content was significantly increased in the presence of tetrodotoxin and decreased sharply following veratridine application. The systemic injection of a general anaesthetic, chloral hydrate, led to a large and prolonged increase in extracellular glucose levels. The brain extracellular glucose concentration was estimated by comparing dialysate glucose efflux over a range of inlet glucose concentrations. A mean value of 0.47 mM was obtained in five animals. The results are discussed in terms of the coupling between brain glucose supply and metabolism. The changes observed in extracellular glucose levels under various conditions suggest that supply and utilization may be less tightly linked in the awake rat than has previously been postulated. PMID- 1431899 TI - Recovery of cholinergic phenotype in the injured rat neostriatum: roles for endogenous and exogenous nerve growth factor. AB - Polyclonal antibodies against recombinant human nerve growth factor (rhNGF) potently inhibited PC12 neurite outgrowth, blocked high-affinity 125I-rhNGF binding but not its receptor, and cross-reacted with rat, mouse, and human nerve growth factor (NGF) but not with brain-derived neurotrophic factor, neurotrophin 3, ciliary neurotrophic factor, insulin-like growth factor, epidermal growth factor, or activin A. Immunocytochemistry revealed many NGF-positive neurons in the rat neostriatum. The NGF-positive neurons disappeared by 3 days after mechanical injury to the neostriatum and were replaced by intensely NGF- and glial fibrillary acidic protein-positive astrocytes. Enzyme-linked immunosorbent assay measurements revealed that the NGF content of the injured striatum was elevated by eightfold 3 days postinjury and by twofold 2 weeks later. The high affinity choline uptake (HACU) into cholinergic nerve terminals was decreased by 23% at 2 and 4 weeks postinjury, yet choline acetyltransferase (ChAT) activity in these neurons was unchanged at 2 weeks and decreased by 14% at 4 weeks. Daily infusion of 1 microgram of rhNGF into the injury area did not alter the loss of HACU. However, this treatment elevated ChAT activity by 23-29% above intact neostriatal levels and by 53-65% relative to HACU at both survival times. Thus, lesion-induced increases in NGF levels within astrocytes are associated with maintenance of striatal ChAT activity at normal levels following cholinergic injury, even with decreases in HACU. Pharmacologic doses of rhNGF can further augment ChAT activity in damaged cholinergic neurons, showing the usefulness of exogenous NGF even when endogenous NGF is elevated in response to injury. PMID- 1431900 TI - Ethanol and excitotoxicity in cultured cortical neurons: differential sensitivity of N-methyl-D-aspartate and sodium nitroprusside toxicity. AB - Neural injury due to ischemia and related insults is thought to involve the action of excitatory amino acids at N-methyl-D-aspartate receptors, which results in the influx of extracellular Ca2+ and the generation of nitric oxide. Because ethanol inhibits physiologic responses to excitatory amino acids, we examined its effect on toxicity induced by N-methyl-D-aspartate and by the nitric oxide donor sodium nitroprusside in neuron-enriched cultures prepared from rat cerebral cortex. Both N-methyl-D-aspartate and sodium nitroprusside were cytotoxic, as measured by the release of lactate dehydrogenase and by microfluorescent determination of cell viability. Ethanol (3-1,000 mM) protected cultures from N methyl-D-aspartate but not sodium nitroprusside toxicity, and the ability of a series of n-alkanols to reproduce the effect of ethanol was related to carbon chain length. Neuroprotection by ethanol was accompanied by a decrease in the N methyl-D-aspartate-evoked elevation of free intracellular Ca2+ and did not appear to involve gamma-aminobutyric acid- or cyclic GMP-mediated mechanisms. These findings suggest that ethanol inhibits excitotoxicity at an early step in the N methyl-D-aspartate signaling pathway, probably by reducing Ca2+ influx, and not by interfering with the action of nitric oxide. PMID- 1431901 TI - Carboxypeptidase M in brain and peripheral nerves. AB - Carboxypeptidase M (CPM), a plasma membrane-bound enzyme, cleaves C-terminal basic amino acids with a neutral pH optimum. We studied its distribution in human, baboon, and dog brain and in dog peripheral nerves. Areas were dissected, homogenized, centrifuged, and assayed for activity with dansyl-Ala-Arg. The corpus callosum and the pyramidal and optic tract were especially rich in CPM, whereas basal ganglia and cortex had low activity. The identity of the basic carboxypeptidase activity with CPM was shown by similarities in subcellular localization, membrane attachment, substrate hydrolysis, inhibition by a specific basic carboxypeptidase inhibitor, and cross-reaction with anti-human CPM antiserum. This antiserum immunoprecipitated an average of 85% of the activity in human and baboon brain and approximately 66% in dog brain. CPM co-purified with myelin extracted from the brain. Consistent with results obtained in placenta and cultured kidney cells, CPM in the brain appears to be membrane-bound via a phosphatidylinositol glycan anchor. In the peripheral nerves, the specific activity in dog sciatic nerve and in vagus was high (98 and 149 nmol/h/mg of protein, respectively). In immunohistochemical studies, glia in the brain, which appear to be oligodendrocytes or astrocytes, and the outer aspects of myelin sheaths and Schwann cells in sciatic and vagus nerves were stained. We conclude that in some areas of the CNS and the PNS, CPM is closely associated with myelin and myelin-forming cells. Northern blot analysis revealed the presence of mRNA coding for CPM in the brain, showing that the enzyme is indeed synthesized there. PMID- 1431902 TI - Role of thapsigargin-sensitive intracellular Ca2+ pools in secretion induced by muscarinic agonists in porcine adrenal chromaffin cells. AB - The role of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-sensitive Ca2+ pools in secretion, induced by muscarinic agonists in porcine adrenal chromaffin cells, was studied. Activation of muscarinic receptors, as in other species, was found to increase inositol phosphate production including that of Ins(1,4,5)P3. Treatment of cells with thapsigargin, which is known to deplete Ins(1,4,5)P3 sensitive Ca2+ pools, eliminated the initial transient component of increases in the cytosolic free Ca2+ concentration ([Ca2+]in) induced by the muscarinic agonist, methacholine, in both the presence and the absence of extracellular Ca2+. Thapsigargin treatment also decreased methacholine-induced secretion by about 30% in the presence of extracellular Ca2+ and essentially eliminated secretion that occurred independently of extracellular Ca2+ (which was about 30% of the secretory response that occurred in the presence of extracellular Ca2+). Thapsigargin itself had no effect on inositol phosphate production. These results indicate that about 30% of muscarinic agonist-induced secretion is mediated by the release of Ca2+ from Ins(1,4,5)P3- and thapsigargin-sensitive intracellular Ca2+ pools. These results also suggest that Ca2+ influx activated by muscarinic agonists is not due to depletion of intracellular Ca2+ pools, as prior depletion of these pools had no effect on the portion of the methacholine-induced secretory response and [Ca2+]in signal that was dependent on extracellular Ca2+. PMID- 1431903 TI - Extracellular striatal concentrations of endogenous 3,4-dihydroxyphenylalanine in the absence of a decarboxylase inhibitor: a dynamic index of dopamine synthesis in vivo. AB - Basal levels of endogenous 3,4-dihydroxyphenylalanine (DOPA) were detected by HPLC coupled with coulometric detection in dialysates from freely moving rats implanted 48-72 h earlier with transversal dialysis fibers in the dorsal caudate. Because decarboxylase inhibitor is absent in the Ringer's solution, this method allows monitoring of basal output of dopamine (DA) and 3,4-dihydroxyphenylacetic acid, as well as DOPA. Extracellular DOPA concentrations were reduced by the tyrosine hydroxylase inhibitor alpha-methylparatyrosine (200 mg/kg, i.p.) and by the dopaminergic agonist apomorphine (0.25 mg/kg, s.c.). The dopaminergic antagonist haloperidol (0.2 mg/kg, s.c.) stimulated DOPA output by about 60% over basal values. Gamma-Butyrolactone, at doses of 700 mg/kg, i.p., which are known to block dopaminergic neuronal firing and which reduce DA release, stimulated DOPA output maximally by 130% over basal values. Tetrodotoxin, which blocks DA release by blocking voltage-dependent Na+ channels, increased DOPA output maximally by 100% over basal values. The results indicate that basal DOPA can be detected and monitored in the extracellular fluid of the caudate of freely moving rats by transcerebral dialysis and can be taken as a dynamic index of DA synthesis in pharmacological conditions. PMID- 1431904 TI - Effects of electroconvulsive shock on tetrahydrobiopterin and GTP-cyclohydrolase activity in the brain and adrenal gland of the rat. AB - The effects of a single and repeated electroconvulsive shock (ECS) (300 mA, 0.2 s) on tetrahydrobiopterin (BH4) levels and GTP-cyclohydrolase activity in the brain and adrenal glands of rats were examined. Twenty-four hours after the last ECS treatment (one/day for 7 days), biopterin levels were significantly elevated in the locus coeruleus, hippocampus, frontal cortex, hypothalamus, ventral tegmental area, and adrenal gland. There were no changes in biopterin levels after a single application of ECS. GTP-cyclohydrolase activity was significantly increased in the locus coeruleus, frontal cortex, hippocampus, hypothalamus, and adrenal gland 24 h after repeated ECS and remained elevated in certain tissues up to 8 days after the last treatment. Kinetic analysis of adrenal and locus coeruleus GTP-cyclohydrolase 1 day after 7 days of ECS showed significant changes in both Km and Vmax values. These data suggest that the long-term increases in BH4 levels and GTP-cyclohydrolase activity after repeated ECS may play a part in the mediation of the antidepressant effects of ECS. PMID- 1431905 TI - Muscarinic acetylcholine receptor enhances phosphatidylcholine hydrolysis via phospholipase D in bovine chromaffin cells in culture. AB - Although it is well-established that inositol-containing lipids serve as precursors of intracellular second messenger molecules in chromaffin cells, we describe some findings that show the formation of diacylglycerol from phosphatidylcholine in response to agonist-mediated stimulation. Stimulation of chromaffin cells by acetylcholine produced a high turnover of phosphatidylcholine, as suggested by the release of [3H]choline derived from [3H] phosphatidylcholine in experiments performed with [3H]choline chloride-prelabeled cells. An enhanced breakdown of phosphatidylcholine was also inferred from the finding of an increased formation of [3H]diacylglycerol in chromaffin cells prelabeled with [3H]glycerol. The diacylglycerol mass that accumulated after stimulation showed a distinct temporal course and seemed to exceed the mass that has been reported to be derived from phosphatidylinositol. In keeping with the purported origin from phosphatidylcholine, diacylglycerol showed a high content in [3H]oleate molecular species. Phospholipase D activity measurements and experiments performed in the presence of propranolol (an inhibitor of phosphatidic acid:phosphohydrolase) suggested that phosphatidylcholine is hydrolyzed by a phospholipase D activity, producing phosphatidic acid, which is subsequently degraded to diacylglycerol, rather than by a phospholipase C. Incubation of chromaffin cells in the presence of atropine before addition of acetylcholine showed complete inhibition of the increased formation of [3H] diacylglycerol, whereas d-tubocurarine failed to do so. Taken together, these results suggest that acetylcholine activates phosphatidylcholine breakdown and diacylglycerol formation in chromaffin cells via a muscarinic-type receptor. PMID- 1431907 TI - Possible regulation of caffeine-induced intracellular Ca2+ mobilization by intracellular free Na+. AB - To gain some understanding of the regulatory mechanism involved in caffeine induced Ca2+ release in adrenal chromaffin cells, we took advantage of the paradoxical observation that removal of divalent cations potentiated the secretory response to caffeine. We measured the concentration of cytosolic free Ca2+ ([Ca]in) in isolated cat chromaffin cells, by fura-2 microfluorometry, to see whether there was any correlation between the secretory response and the rise in [Ca]in. The caffeine-induced [Ca]in rise and catecholamine secretion were increased by treatment of cells with a divalent cation-deficient solution. These potentiated responses were strongly inhibited either by pretreatment with ryanodine, by the reduction of the external Na+ concentration, or by the addition of Ca2+ channel blockers. Removal of divalent cations caused a large rise in the cytosolic free Na+ concentration ([Na]in), which was measured using SBFI microfluorometry. This rise in [Na]in was reduced either by adding Ca2+ channel blockers or by reducing the external Na+ concentration. These results show a good correlation between caffeine-induced Ca2+ release and [Na]in at the time of stimulation, suggesting that caffeine-induced Ca2+ release is regulated by [Na]in. PMID- 1431906 TI - Regulation of carboxypeptidase E by membrane depolarization in PC12 pheochromocytoma cells: comparison with mRNAs encoding other peptide- and catecholamine-biosynthetic enzymes. AB - PC12 cells, a rat pheochromocytoma cell line, have been found to express carboxypeptidase E (CPE) enzymatic activity and CPE, furin, and peptidylglycine alpha-amidating monooxygenase (PAM) mRNAs. PC12 cells secrete CPE activity in response to depolarization induced by 50 mM KCl. Short-term (1- to 3-h) treatments of PC12 cells with KCl stimulates the secretion of CPE but does not appear to stimulate the synthesis of new CPE protein, based on the measurement of CPE activity and incorporation of [35S]-Met into CPE. Also, CPE mRNA is not altered by 2-h treatments with KCl. In contrast, prolonged treatment (24-48 h) of PC12 cells with 50 mM KCl continues to stimulate the secretion of CPE activity, without altering the cellular level of CPE. Levels of CPE mRNA are significantly elevated after long-term treatment of the cells with KCl, with increases of 35% after 5 h and 55-75% after 24 to 72 h of treatment. The level of PAM mRNA is also elevated approximately 70% after 24 h of stimulation with KCl. In contrast, the mRNA levels of furin and dopamine beta-hydroxylase (DBH) do not change on treatment of PC12 cells with KCl. These findings indicate that long-term depolarization, which leads to a prolonged stimulation of PC12 cells to secrete CPE, also stimulates the synthesis of CPE and PAM but not furin or DBH. PMID- 1431908 TI - Alteration of neuroblastoma ganglioside metabolism by retinoic acid. AB - Cellular differentiation is often associated with striking changes in ganglioside metabolism. Because retinoic acid causes cellular differentiation in vitro, we have characterized its effect on ganglioside synthesis and shedding by LAN-5 human neuroblastoma cells. Three major observations were made: (a) 20 microM retinoic acid caused a marked (twofold) increase in cellular ganglioside content, with a slight relative enhancement in GD1a and GT1b synthesis, (b) ganglioside shedding increased in parallel with increased cellular ganglioside content, and also, unexpectedly, (c) retinoic acid caused a quantitatively similar increase in content of cell membrane phospholipids, which are also shed. We conclude that enhanced ganglioside synthesis and shedding by retinoic acid are part of a previously undescribed generalized stimulatory effect on membrane lipid metabolism. PMID- 1431909 TI - Specific irreversible monoamine oxidase B inhibitors stimulate gene expression of aromatic L-amino acid decarboxylase in PC12 cells. AB - The effect of some selective monoamine oxidase (MAO) inhibitors on aromatic L amino acid decarboxylase (AADC) gene expression in PC12 cells has been examined. Irreversible MAO B inhibitors [(-)-deprenyl, pargyline, and MDL 72,974A] stimulated AADC gene expression, whereas a selective irreversible MAO A inhibitor (clorgyline) and a reversible MAO B inhibitor (Ro 19-6327) had no effect. Because there is no apparent MAO B activity in PC12 cells, it is postulated that there is a novel site of action for these MAO B inhibitors and that the pharmacological profile of this site matches that of neuroprotective MAO B inhibitors. Finally, it is suggested that the stimulation of AADC gene expression may be relevant to the antiparkinsonian effects of MAO B inhibitors. PMID- 1431910 TI - An alternative secretase cleavage produces soluble Alzheimer amyloid precursor protein containing a potentially amyloidogenic sequence. AB - Cell culture studies have shown that the Alzheimer amyloid precursor protein (APP) is secreted after full-length APP is cleaved by a putative secretase at the Lys16-Leu17 bond (secretase cleavage I) of the amyloid peptide sequence. Because this cleavage event is incompatible with amyloid production, it has been assumed that secreted APP cannot serve as a precursor of the amyloid depositions observed in Alzheimer's disease. Here we show that in neuronally differentiated PC12 cells and human kidney 293 cell cultures a portion of the secreted extracytoplasmic APP reacted specifically with both a monoclonal antibody recognizing amyloid protein residues Leu17-Val24 and a polyclonal antiserum directed against amyloid protein residues Ala21-Lys28. Furthermore, this APP failed to react with antisera recognizing the cytoplasmic domain of the full-length protein. These data indicate the presence of an alternative APP secretase cleavage site (secretase cleavage II), C-terminal to the predominant secretase cleavage I. Depending on the exact location of cleavage site II, potentially amyloidogenic secreted APP species may be produced. PMID- 1431911 TI - Lithium enhances accumulation of [3H]inositol radioactivity and mass of second messenger inositol 1,4,5-trisphosphate in monkey cerebral cortex slices. AB - We previously reported that lithium, in the presence of acetylcholine, increased accumulations of inositol 1,4,5-trisphosphate and inositol 1,3,4,5 tetrakisphosphate in brain cortex slices from the guinea pig, rabbit, rat, and mouse. In the mouse and rat, the Li(+)-induced increases required supplementation of the medium with inositol. This probably relates to the following facts: (a) Brain cortices of the mouse and rat contain in vivo concentrations of inositol half of that of the guinea pig. (b) Incubated rat brain cortex slices are depleted of inositol by 80%. (c) The slices require 10 mM inositol supplementation to restore in vivo concentrations. We now show that in monkey brain cortex slices, therapeutic concentrations of Li+ increase accumulation of inositol 1,4,5-trisphosphate. The inositol 1,3,4,5-tetrakisphosphate level is not increased. Neither inositol nor an agonist is required. The same effects are seen whether inositol 1,4,5-trisphosphate is quantified by the [3H]inositol prelabeling technique or by mass assay, although mass includes a pool of inositol 1,4,5-trisphosphate that is metabolically inactive. Thus, in a therapeutically relevant model for humans, Li+ increases inositol 1,4,5-trisphosphate levels in brain cortex slices, as was previously seen in lower mammals at non-rate-limiting concentrations of inositol. PMID- 1431913 TI - Factors influencing survivorship of the femoral component after primary low friction hip arthroplasty. AB - Two hundred sixty-seven consecutive primary low-friction arthroplasties, followed for 5-18 years after surgery, were studied to assess the factors influencing survivorship of the femoral component, using the Kaplan-Meier method. The end point of survivorship was defined radiographically in two ways: incipient failure (subsidence of the femoral component of > or = 2 mm) and definite failure (progressive change of position). Twenty-two femoral components developed incipient failure, and twelve of these advanced to definite failure. A canal filling ratio of the stem of > or = 75%, cement extent distal to the stem tip of > or = 1 cm, use of an intramedullary bone plug, and an exaggerated valgus alignment of the stem correlated positively with survivorship of the femoral component. Calcar resorption and atrophy of the femoral cortex after surgery were associated with aseptic loosening of the femoral component. PMID- 1431912 TI - Metabotropic excitatory amino acid receptor activation stimulates phospholipase D in hippocampal slices. AB - Metabotropic excitatory amino acid (EAA) receptors are coupled to effector systems through G proteins. Because various G protein-coupled receptors stimulate the hydrolysis of phosphatidylcholine by phospholipase D (PLD), we examined the possibility that metabotropic EAA receptors exist that are coupled to the activation of PLD. We found that the selective metabotropic glutamate receptor (mGluR) agonists 1S,3R-amino-1,3-cyclopentanedicarboxylic acid (ACPD) and 1S,3S ACPD, but not the inactive isomer, 1R,3S-ACPD, induce a concentration-dependent increase in PLD activity in hippocampal slices. Selective ionotropic glutamate receptor (iGluR) antagonists did not block 1S,3R-ACPD-induced PLD stimulation. Furthermore, although selective iGluR agonists did not activate this response, the nonselective mGluR-iGluR agonists, ibotenate and quisqualate, caused significant increases in PLD activity (all in the presence of iGluR antagonists). L-2-Amino-3-phosphonopropionic acid, which blocks the mGluR that is coupled to phosphoinositide hydrolysis in various brain regions, activates PLD to the same extent as the active isomers of ACPD. These data suggest that metabotropic EAA receptors exist in hippocampus that are coupled to PLD activation and are pharmacologically distinct from phosphoinositide hydrolysis-coupled mGluRs. PMID- 1431914 TI - Total hip arthroplasty in active golfers. AB - Total hip arthroplasty (THA) is commonly performed in an older population, for whom gold is often the only form of exercise. Members of the Hip Society do not feel that golfers have increased rates of complications after THA when compared to nongolfers and permit their patients to play gold with a THA. Most golfers will see their handicaps increase after total joint arthroplasty, although this does not appear to be a function of drive length. Most golfers with a successful primary total joint arthroplasty will not have pain while playing golf but will likely experience a mild ache in the hip region after playing. Hybrid and uncemented primary THAs appear to have lower rates of radiographic loosening in active golfers when compared to cemented THAs. However, symptoms of pain while playing or after playing do not differ among these groups, despite this radiographic difference. PMID- 1431915 TI - Survivorship of cemented total hip arthroplasty in patients 50 years of age or younger. AB - One hundred fifty-six Charnley low-friction arthroplasties performed in patients 50 years of age or younger are reviewed. Excluding sepsis, survivorship analysis showed a 12% probability of mechanical failure at 10 years. The detailed clinical and radiological results of 130 hips with a 3-16-year follow-up period are presented. Revision surgery was required in 14 hips (10.8%), for the following reasons: sepsis (2.3%), loose sockets (2.3%), loose stems (5.4%), and stem fracture (0.8%). Evidence of radiological loosening indicative of pending failure was present in 14 hips (12.0%). At 10 years the predicted failure rate of the surviving hips was 12%. PMID- 1431916 TI - Clinical and radiographic analysis of the uncemented LSF total hip arthroplasty. AB - Forty-nine consecutive uncemented porous-coated LSF total hip prostheses were implanted in 41 patients and studied prospectively. Clinical rating as described by Harris was performed preoperatively, at 6 months and 1 year postoperatively, and annually thereafter. Anteroposterior and lateral radiographs were obtained preoperatively, immediately postoperatively, at 6 and 12 months, and annually thereafter. At the most recent follow-up visit, patients were evaluated clinically and radiographically utilizing the format recently recommended by the Hip Society. A patient satisfaction questionnaire was also completed. The follow up period averaged 37 months (range, 24-48 months). Preoperative hip scores averaged 38 (range, 18-68) and improved to 93 at the most recent follow-up visit (range, 76-100). The incidence of mild pain was 14% at 1 year and 4% at 2 years or more. The incidence of limp was 16% slight and 8% moderate at 1 year, and 12% slight and 2% moderate at 2 years or more. Surgical fit was objectively graded as excellent in 61%, good in 33%, and poor in 6%. The authors were unable to correlate surgical fit with clinical scores or radiographic findings. According to radiographic criteria, all components were judged to be stable and 86% were judged to demonstrate objective signs of osseointegration. Patient satisfaction with the procedure was 100%. All patients stated that the procedure increased their function and decreased their pain and need for medication. Compared to a normal hip, in terms of symptoms and function, the patients rated their postoperative hip at 85% (range, 50-100%). Compared to their level of activity before their hip was symptomatic, they rated their current activity level as 83% (range, 50-100%). PMID- 1431917 TI - Influential factors in cemented acetabular cup loosening. AB - To delineate further the cause of acetabular loosening in a group of 238 total hip arthroplasties performed between 1980 and 1982, the authors subjected those total hip arthroplasties to a multifactorial analysis utilizing the log normal model. Data collected on each patient consisted of age, sex, weight at the time of surgery, diagnosis, cement thickness between zones 1 and 2 and between zones 2 and 3, polyethylene thickness, lateral tilt, and metal backing of the acetabular components. The acetabulum was considered a failure by radiographic loosening with migration greater than 5 mm, revision in patients younger than 60 years of age (P = 0.154), or when the acetabular cup was metal-backed (P = .001). PMID- 1431918 TI - Cementless hip arthroplasty in diastrophic dysplasia. AB - Diastrophic dysplasia results in severe disproportionate growth failure, generalized joint dysplasia, and early osteoarthrosis of the hips. A total hip arthroplasty is often necessary in patients afflicted with diastrophic dysplasia by time they reach early middle age. During 1983-1988, total hip arthroplasties were performed on six women and four men (15 hips) with diastrophic dysplasia at the Orthopaedic Hospital of the Invalid Foundation. The mean age of the patients at the time of operation was 37 years and the mean height was 133 cm. A Lord endoprosthesis was used in nine hips and a Biomet endoprosthesis in six. Cementless fixation was used in all cases. Autogenous bone grafting to the acetabulum was performed in six hips. Simultaneous corrective osteotomy of the proximal femur and transposition of the greater trochanter was performed in three cases. Soft tissue release and tenotomies were performed in 10 hips. The average follow-up period was 5 years. Overall clinical results were good, with marked relief of pain and improvement of hip joint mobility. Aseptic loosening of the acetabular component was noted in two hips. As for complications, two femoral nerve paresis and two perioperative fractures of the proximal femur occurred, which all healed. PMID- 1431919 TI - Measurement of acetabular component migration using two-dimensional radiography. AB - The relationships between apparent acetabular component migration, choice of anatomic landmarks, and changes in rotation of the pelvis were determined by examining radiographs of a pelvic model in multiple projections. The minimum apparent migration associated with transverse and longitudinal rotation of 5 degrees from neutral was 2 mm. The least apparent migration was noted when the teardrop was used as the principal anatomic landmark. Determination of component migration in clinical studies from serial radiographs involves a minimum projection and magnification error of 2 mm. PMID- 1431920 TI - Cementless total hip arthroplasty using a porous-coated prosthesis for bone ingrowth fixation. 3 1/2-year follow-up. AB - The clinical and radiologic results of a consecutive series of 59 patients (69 hips) who had primary total hip arthroplasty using cementless prostheses was studied. Harris-Galante acetabular and femoral prostheses, which have a porous fiber-metal mesh coating intended to encourage bone ingrowth fixation, were used in all cases. Two femoral components were revised during the follow-up period, one for aseptic loosening and the other for late septic loosening. In the remaining 67 hips, the average Harris hip score rose from a preoperative 52 to 94 at the last follow-up examination (average follow-up period, 44 months). Eighty eight percent of these hips had an excellent result (Harris hip score of 90 or more). Radiologic analysis demonstrated that all the acetabular components were stable. Eighty-three percent of the femoral components appeared to have stable bone ingrowth fixation, five components (7%) had stable fibrous ingrowth, and seven (10%) were unstable. Parallel radiodense lines were seen around the smooth portion of the stem in 93% of hips, but this finding appeared to have no clinical importance. Significant stress shielding of the proximal femur was seen in 16% of hips. Endosteal lysis of the distal femur occurred in 22% of hips, including large lesions in two patients who will require future revision surgery because of femoral diaphysis weakening. Femoral lysis was not associated with hip or thigh pain and was most common in young, male patients who had high activity levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1431921 TI - In vitro study of initial stability of a conical collared femoral component. AB - This in vitro experimental study compared the initial stability of an uncemented conical collared femoral component to that of the same component with the collar removed. The two configurations examined simulated joint resultant forces encountered in single leg stance and stair climbing. For the simulated single leg stance loads, the data do not allow any inferences about relative component stability. With the exception of one collarless control, all micromotion for single leg stance loading was under 150 microns, measured approximately 1.5 cm below the resection line. For scaled stair-climbing loads, however, the conical collared component group was significantly more stable than the collarless control group in transverse (primarily rotational) micromotion. The overall average measured transverse motion for the collarless control group was more than 3.7 times greater than that of the conical collar group at scaled stair-climbing loads. The two conical collared components loaded to full peak stair-climbing load (2,100 N) exhibited micromotion under 160 microns. The results suggest that the conical collar may improve stability of an uncemented prosthesis under loads that include an out-of-plane (rotational) component. PMID- 1431922 TI - Use of an antibiotic impregnated polymethyl methacrylate intramedullary spacer for complicated revision total hip arthroplasty. AB - Revision total hip arthroplasty is frequently necessary in the presence of significant proximal femoral bone loss, periprosthetic fracture, or infection. In these situations, optimal reconstruction may sometimes warrant the use of special implants, including bone grafts. The emergent presentation of these cases or unexpected findings at the time of surgery can preclude the use of these treatment options. In cases of periprosthetic sepsis, delayed reimplantation may be the most successful approach to eradicate infection. In seven of these complicated revision total hip arthroplasties, the authors used an antibiotic impregnated intramedullary polymethyl methacrylate spacer with delayed prosthetic reimplantation to allow for the use of these methods. Benefits of this technique include uncompromised radiographic evaluation of the proximal femur for design of a custom implant, if needed, stabilization of the proximal femur facilitating early mobilization of the patient in the case of periprosthetic fracture, and local delivery of antibiotics to the wound in the case of infection. The author's ability to reconstruct these total hip arthroplasties complicated by bone deficiency, fracture, and sepsis, was significantly improved with this use of this technique. PMID- 1431923 TI - Preoperative planning for total hip arthroplasty. Quantitating its utility and precision. AB - This study evaluated the usefulness and accuracy of preoperative planning for cemented and cementless total hip arthroplasty (THA). The authors conducted a prospective study of 110 consecutive primary cases in which surgeons recorded the preoperative plan and what occurred in each case. Measured variables included estimated magnification, acetabular cup and femoral stem size, planned lengthening, and anticipated problems. Preoperative estimates of magnification frequently differed from actual magnification, and in 17% of cases it affected choice of implant size. Preoperative bone morphology did not correlate with type of femoral stem fixation. Implant sizing was predicted from the preoperative plan for 62% of acetabular cups, 78% of cemented stems, and 42% of the cementless stems. Leg-length equalization was a goal in only 70% of cases. Anticipated problems focused on anatomic variations, but intraoperative problems involved technique and equipment. The authors conclude that surgeons need better methods to estimate magnification and bone morphology from preoperative radiographs. Preoperative planning may not reduce intraoperative complications, which can arise from unanticipated technique and equipment mishaps. PMID- 1431924 TI - A new femoral cement restrictor. AB - The authors report on the clinical trial of a new femoral cement restrictor for use during hip arthroplasty. Instrumentation and technique are described. The restrictor has three components made of high-density polyethylene that fit one inside the other and is available in small, medium, and large sizes. The advantages of this new restrictor are ease of use and secure fixation in the femoral canal when deployed. Because of its inherent strength and design, small particles do not break off during insertion. The apex of the restrictor points proximally and is cupped. This helps in centralizing the stem. It also assists in obtaining good cement pressurization as it does not distally migrate in the femoral canal when pressurization is attempted. Also, no cement escapes distally beyond it. Furthermore, should revision surgery be required, the restrictor can be easily removed without the need for windowing the femoral cortex. PMID- 1431925 TI - Intramedullary plugs in total hip arthroplasty. A comparative study. AB - The quality of cement packing was radiographically evaluated using three different types of intramedullary plugs in 77 total hip arthroplasties. The Thackray polyethylene plug (38 mm, disc-shaped), with its large and flexible diameter, was best able to seal the femoral canal and produced significantly better cement packing compared to both the autologous bone plug and the Richard polyethylene plug (18.5 mm, bullet-shaped). PMID- 1431926 TI - Surgical management of gonarthrosis in patients with poliomyelitis. AB - The authors reviewed nine cases of degenerative disease of the knee in patients with a history of poliomyelitis. All patients were treated with a cemented total knee arthroplasty. The average follow-up period was 6.8 years (range, 6 months to 13 years), and the average follow-up knee score using the Hospital for Special Surgery rating scale was 70. Three of the patients required revision total knee arthroplasty to a more constrained implant. Pain relief was predictably very good and knee stability was initially improved. However, many of the patients suffered a decline in ambulatory ability with time. PMID- 1431927 TI - Lateral patellar release in knee arthroplasty. Effect on wound healing. AB - A prospective study analyzing the effects of intraoperative lateral patellar release for patellar instability in total condylar knee arthroplasty demonstrated that lateral release was successful in preventing postoperative patellar instability. Division of the superolateral geniculate vessels resulted in an increased incidence of wound discoloration (P < .01) and superficial wound infection (P < .05). Perioperative transcutaneous measurement of the skin oxygen tension demonstrated an objective reduction in lateral wound edge skin viability following lateral release (P < .02). A lower threshold for performing lateral patellar release is necessary. To preserve the viability of the lateral skin edge, lateral release should be performed using the intracapsular approach with preservation of the superolateral geniculate vessels. PMID- 1431928 TI - The effect of central stem and stem length on micromovement of the tibial tray. AB - The effects of a central stem and its length on cementless tibial tray micromovement were investigated using preserved cadaver tibial specimens. For axial loading tests, cyclical compressive loads ranging 50-1000 N were applied to the anterolateral portion of the implanted tray. With subsidence on the loaded side and lift-off on the contralateral side, micromotions on both sides and bending of the tray were measured. The three groups consisted of a stemless group, a 7.5 cm (short) central stem group, and a 15 cm (long) central stem group. For shear loading tests, shear loads ranging 20-250 N were applied to the central portion of the posterior rim of the tray anteriorly for 1,000 cycles. Displacement values for subsidence and micromotion were measured on the medial and lateral side of the trays and compared for each group. For axial tests, the long stem minimized subsidence and lift-off (P < .05) when compared to the stemless group. Although the short stem also tended to prevent contralateral lift off, no significant difference was shown when compared to the stemless group. However for shear loading, both central stem lengths significantly reduced subsidence and micromotion (P < .05). The authors conclude that the tibial tray with a long stem can achieve better initiation fixation of the implant to bone when compared to the short stem and no stem groups. PMID- 1431929 TI - Severe metallosis due to abnormal abrasion of the femoral head in a dual bearing hip prosthesis. A case report. AB - The authors report on a patient with a case of severe metallosis due to an abnormal abrasion of the femoral head. A primary arthroplasty was performed using a dual bearing hip prosthesis with acetabular bone grafting by ceramic screws. At the time of the revision surgery the synovia was black, and an analysis using a scanning electron microscope and scanning electron microscope-electron probe micro-analyzer revealed numerous small particles of small alumina ceramic on the inner surface of the bearing insert of high-density polyethylene. These particles, which came from the broken ceramic screws due to proximal migration of the prosthesis, scraped the femoral head away. A line and area analysis of the black synovia revealed that the synovia contained metal particles of a cobalt chromium alloy as well as a cobalt ion. The patient's serum showed elevated concentrations of cobalt, chromium, and molybdenum that dramatically reduced 2 months after the revision surgery. PMID- 1431930 TI - Ankle pain following total knee arthroplasty. A case report. AB - The authors present their experience with four cases of ankle pain occurring in the immediate postoperative period after total knee arthroplasty. In a 40-month period, the authors performed 87 total knee arthroplasties. In the first 28 cases, an extramedullary alignment rod was used and there were no instances of ankle pain (0%). In the next 30 cases, an intramedullary alignment rod was employed and there were three cases of moderate to severe ankle pain (10%). In the last 29 cases, the medullary canal was decompressed, irrigated, and aspirated prior to insertion of the alignment rod. In this group there was only one case of mild ankle discomfort (3.5%). An extensive investigation was made into one of the cases in which the intramedullary alignment rod was used but the canal was not aspirated. Information from this case investigation, observation of the three subsequent cases, and the notation of a decrease in the incidence of ankle pain once aspiration was routinely used are reported. The unproven hypothesis that ankle pain may result from compression of the marrow contents into the bone interstices is presented for consideration. Three of the four cases of ankle pain reported here were spontaneously resolved within 9 months after surgery. PMID- 1431931 TI - Late disassembly of a modular acetabular component. A case report. AB - Disassembly of metal-backed acetabular components used for total hip arthroplasty is becoming more common in both preassembled and modular designs. This complication is usually associated with a dislocation of the femoral component or other radiographic evidence of dissociation. A case of late disassembly of the acetabular component without dislocation or radiographic evidence is presented. The authors believe this complication should be considered, along with infection and aseptic loosening, in all cases of late development of pain following total hip arthroplasty. PMID- 1431932 TI - Antitumor agents, 129. Tannins and related compounds as selective cytotoxic agents. AB - Fifty-seven tannins and related compounds, including gallotannins, ellagitannins, and condensed and complex tannins, were evaluated for their cytotoxicities against human tumor cell lines, including malignant melanoma, lung carcinoma, ileocecal adenocarcinoma, epidermoid carcinoma, malignant melanoma, and medulloblastoma cell lines. Among them, chebulagic acid [1], geraniin [2], sanguiin H-11 [3], 4,5-di-O-galloylquinic acid [12], 1,3,4,5-tetra-O galloylquinic acid [15], 1(beta)-O-galloylpedunculagin [24], furosin [29], castalagin [38], sanguiin H-2 [34], vescalagin [39], grandinin [40], phyllyraeoidin A [42], (-)-epicatechin 3-O-gallate [50], cinnamtannin B2 [55], and acutissimin A [56] exhibited moderate selective cytotoxicity against PRMI 7951 melanoma cells with ED50 values in the range of 0.1-0.8 microgram/ml. Selective cytotoxicities against the melanoma cells were also observed for strictinin [22], pedunculagin [23], eugeniin [25], elaeocarpusin [28], punicacortein C [37], casuarinin [41], sanguiin H-6 [43], procyanidin B-2 3,3'-di O-gallate [51], procyanidin C-1 3,3',3"-tri-O-gallate [52], and cinnamtannin B1 [54] with ED50 values of 1-4 micrograms/ml. All of the tannins were found to be inactive (greater than 10 micrograms/ml) against lung carcinoma (A-549), ileocecal adenocarcinoma (HCT-8), epidermoid carcinoma of nasopharnyx (KB), and medulloblastoma (TE-671) tumor cells. PMID- 1431933 TI - A bioassay for inhibition of serotonin release from bovine platelets. AB - A bioassay was developed to study agents capable of inhibiting the release of serotonin from bovine blood platelets. It is a simple, inexpensive, and reproducible high-throughput bioassay suitable for quality control of feverfew, Tanacetum parthenium, a crude drug with proven migraine prophylactic activity that is being considered for governmental registration and regulation. The bioassay, which requires no experimental animals or human subjects, was used to assess the in vitro activity of T. parthenium samples grown from seed obtained from 10 different regions of Europe. The activity was found to vary significantly within and between samples, with no geographical correlation. Serotonin release inhibition was shown to be significantly correlated with the content of the germacranolide sesquiterpene lactone, parthenolide, although other sesquiterpene lactones from this plant and other members of the Asteraceae were also shown to be active. The activities of six other species of Tanacetum, as well as of Artemisia absinthium (wormwood) and Zingiber officinale (ginger), and two commercial drugs for migraine prophylaxis, verapamil hydrochloride and propranolol hydrochloride, were also assessed. The relevance of the bovine platelet serotonin release inhibition bioassay to antimigraine research is discussed. PMID- 1431934 TI - New bioactive metabolites from a freshwater isolate of the fungus Kirschsteiniothelia sp. AB - The new cytotoxic naphthoquinone dimer kirschsteinin [5], two new chlorinated diphenyl ethers 8 and 9, three known naphthoquinone derivatives 1, 2, and 7, a monoacetyl derivative of 2, and the (-)-enantiomer of O-methylasparvenone [4], have been isolated from a previously undescribed species of Kirschsteiniothelia. The structures of these compounds were assigned primarily by nmr studies and by spectral comparisons. PMID- 1431935 TI - Molluscicidal acridone alkaloids from Angostura paniculata: isolation, structures, and synthesis. AB - Two novel acridone alkaloids, cuspanine [1] and cusculine [2], were isolated from the CH2Cl2 extract of the leaves of Angostura paniculata (Rutaceae). Their structures were established as 1-hydroxy-2,3,5,6-tetramethoxy-9-acridone for 1 and 1,2,3,5,6-pentamethoxy-9-acridone for 2 by means of spectroscopic studies, in particular nmr. These structural assignments were confirmed by synthesis, using a direct metallation method as a key reaction. Both alkaloids exhibited moderate molluscicidal activity against an aquatic snail, Biomphalaria glabrata, and cytotoxicity against several types of carcinoma cell lines. PMID- 1431937 TI - Stereoselective synthesis and antimalarial activity of alpha-artelinic acid from artemisinin. AB - alpha-Artelinic acid [8], a potent, stable, and water-soluble antimalarial agent, has been synthesized from artemisinin [1], the sesquiterpene lactone endoperoxide isolated from Artemisia annua. The blood schizontocidal antimalarial activity of alpha-artelinic acid evaluated against Plasmodium knowlesi is also reported. PMID- 1431936 TI - (+)-4 beta-hydroxyhernandulcin, a new sweet sesquiterpene from the leaves and flowers of Lippia dulcis. AB - From the leaves and flowers of Lippia dulcis collected in Panama, a new sweet sesquiterpene identified as (+)-4 beta-hydroxyhernandulcin [2] was isolated, accompanied by (+)-hernandulcin [1], (-)-epihernandulcin [3] (a novel natural product), and 6-methyl-5-hepten-2-one [4]. Acteoside (verbascoside) [5], a known bitter phenylpropanoid glycoside, was isolated from the flowers of L. dulcis. The structure of (+)-4 beta-hydroxyhernandulcin was established by interpretation of its spectral data. PMID- 1431938 TI - Vasoconstrictor activity of 8-O-acetylharpagide from Ajuga reptans. AB - The traditional therapeutic indications for the use of Ajuga reptans (Labiatae) have been investigated. The H2O-soluble part of a crude and partially purified MeOH extract and two isolated iridoids (8-O-acetylharpagide and harpagide), were tested for a biological activity on isolated smooth muscle preparations from guinea pig. PMID- 1431939 TI - A new acylated N-glycosyl lactam from Aristolochia contorta. AB - A new acylated glycoside isolated from the roots of Aristolochia contorta (Aristolochiaceae), has been characterized as aristolactam N-(6'-trans-p coumaroyl)-beta-D-glucopyranoside [2]. Aristolactam-N-beta-D-glucopyanoside [1] was also isolated from the same source. Compound 2 showed relatively significant antibacterial activity against Gram-positive bacteria, based on disc diffusion and dilution methods. PMID- 1431940 TI - Brominated polyacetylenic acids from the marine sponge Xestospongia muta: inhibitors of HIV protease. AB - The EtOAc extract of the sponge Xestospongia muta collected in Colombus Island, Bahamas, yielded eleven straight-chain unsaturated, polyacetylenic, brominated acids, seven of which were identified on the basis of spectral data, including the unknown acids 2-7. These acetylenic acids are the first known examples that have been shown to inhibit HIV protease, a critical enzyme in the replication of human immunodeficiency virus. PMID- 1431941 TI - The enzymatic decomposition of salicin and its derivatives obtained from Salicaceae species. AB - The enzymatic catalysis of the decomposition of Salicaceae phenolic glucosides was tested using almond beta-glucosidase and rabbit and porcine liver esterases. The beta-glucosidase catalyzed the complete hydrolysis of salicin and salicortin, yielding saligenin and glucose. Salicortin also produced (+)-6-hydroxycyclohexen 2-one (6-HCH). The acylglucosides were not decomposed by the beta-glucosidase. Both esterases catalyzed the decomposition of tremulacin, salicortin, and 2'-O acetylsalicortin, releasing tremuloidin, salicin, and 2'-O-acetylsalicin as the main products, accompanied by 6-HCH and catechol. Tremuloidin and 2'-O acetylsalicin were quite stable under the esterase hydrolysis, and salicin was not decomposed at all. PMID- 1431942 TI - New cytotoxic scalarane sesterterpenes from the Dictyoceratid sponge Strepsichordaia lendenfeldi. AB - Nine sesterterpenes 1-9 have been isolated from a Dictyoceratid sponge, Strepsichordaia lendenfeldi, collected on the Great Barrier Reef, Australia. Seven of these compounds are new, one [4] had been reported previously as a semisynthetic product, and one [5] had been isolated previously from Carteriospongia foliascens. Unambiguous 13C- and 1H-nmr assignments have been made for 1 based on extensive 1D and 2D high field nmr experiments, which enabled 13C-nmr assignments to be made for 2-9. Significant growth inhibitory effects with tested cancer cell lines are reported for compounds 1-8. PMID- 1431943 TI - Characterization of silkworm chlorophyll metabolites as an active photosensitizer for photodynamic therapy. AB - Silkworm excreta containing chlorophyll metabolites have long been used for their medicinal activities in the Far East. The major chlorophyll derivative (CpD) fraction in the Me2CO extract from the silkworm excreta exhibits strong photodynamic action on mice and human tumor cells in vitro. The main CpD component was isolated, purified, and subjected to extensive structural and characterization studies to assess its photodynamic therapeutic activity. According to the spectral analyses, the structure of the major unknown CpD was determined to be 10-hydroxypheophytin a [1]. The CpD component possessed a high quantum efficiency (50%) for the photosensitized production of singlet molecular oxygen, thus providing a molecular basis for its photodynamic therapeutic efficiency. A further advantage is that the "photooxidation/degradation" product(s) from this CpD retains all the characteristics of a photodynamic sensitizer. PMID- 1431944 TI - New phenolic glucosides from the leaves of Eurya tigang. AB - Three new compounds, 6'-O-coumaroyl-1'-O-[2-(4-hydroxyphenyl)ethyl]-beta-D glucopyra nos ide [1] (eutigoside A), 6'-O-coumaroyl-1'-O-[2-(1-hydroxy-4-oxo-2,5 cyclohexadien-1- yl)ethyl]-beta-D-glucopyranoside [2] (eutigoside B), and 6'-O cinnamoyl-1'-O-[2-(1-hydroxy-4-oxo-2,5-cyclohexadien-1-yl)eth yl]- beta-D glucopyranoside [3] (eutigoside C) have been isolated from the leaves of Eurya tigang, along with other known compounds (afzelin, quercitrin, p-coumaric acid, methyl-alpha-D-fructofuranoside, isorengyol, and euryanoside). Their structures were determined by chemical and spectroscopic methods (uv, ir, ms, 1H-1H COSY, and 1H-13C COSY). PMID- 1431945 TI - Further bioactive acetylenic compounds from the Caribbean sponge Cribrochalina vasculum. AB - In addition to the known 3-hydroxydocosa-(4E, 15E)-dien-1-yne [1], 3-hydroxy-16 methyleicos-(4E)-en-1-yne [2], and 3-hydroxy-19-methyleicos-(4E)-en-1-yne [3], the lipophilic extract of the Caribbean sponge Cribrochalina vasculum was shown to contain four new bioactive acetylene metabolites, (3R)-hydroxy-14-methyldocos (4E)-en-1-yne [4], (3R)-hydroxy-16-methyleicos-1-yne [7], (3R)-hydroxy-19 methyleicos-1-yne [8], and docosa-(3E, 15Z)-dien-1-yne [9], whose structures were elucidated on the basis of chemical and spectral studies. The previously unassigned chirality at C-3 of the known compounds 1-3 has been also established as R. PMID- 1431946 TI - Displacement activity of bisbenzylisoquinoline alkaloids at striatal 3H-SCH 23390 and 3H-raclopride binding sites. AB - Fifteen bisbenzylisoquinoline alkaloids (BBIQ) with one ether bridge (thaligrisine [1], berbamunine [2], dimethylgrisabine [3], pampulhamine [4], and methyl-dauricine [5]), with two ether bridges (homoaromoline, isotetrandrine, and obaberine), with one ether bridge and one biphenyl bridge (oxandrine, dimethylpseudoxandrine, pseudoxandrine, and antioquine) or secoderivatives (secoobaberine, secoantioquine, and secolucidine), were tested for their ability to displace 3H-raclopride or 3H-SCH 23390 from their specific dopaminergic binding sites to rat striatal membranes. The most active compounds were found in the group of BBIQs with one ether bridge. Inactive or weakly active compounds were found in this group of BBIQs with one ether bridge and in the other groups. Analysis of tridimensional representations indicates that the differnt activities among the BBIQs with one ether bridge could be related to strong differences between the spatial occupancy of these compounds according to their stereochemistry. PMID- 1431947 TI - Linear diterpenes from the Caribbean sponge Myrmekioderma styx. AB - Four new oxygenated diterpenes 1-4 were isolated from the Caribbean sponge Myrmekioderma styx. The structures of these compounds were deduced by ms, uv, ir, 1H- and 13C-nmr, 1H-1H COSY, XHCORR, and COLOC experiments. Compounds 1-4 are lethal to brine shrimp (Artemia salina). PMID- 1431948 TI - The ocular manifestations of multiple sclerosis. 2. Abnormalities of eye movements. PMID- 1431949 TI - Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study. AB - There is a dearth of longitudinal studies on psychometric and psychiatric change in multiple sclerosis (MS) particularly on the evolution of these abnormalities early in the disease process. A 4 1/2 year follow up study documenting magnetic resonance imaging (MRI), psychometric, and psychiatric abnormalities was undertaken in a group of 48 patients with clinically isolated lesions--for example, optic neuritis--which are frequently the harbinger of MS. At follow up about half the subjects had developed clinically definite MS, with memory deficits becoming apparent. Deficits in attention documented at initial assessment were present but unchanged in those subjects who still had a clinically isolated lesion status. However, after MS was categorised into a relapsing-remitting or chronic progressive course, patients with a chronic progressive course were found to have significantly deteriorated with regard to auditory attention tasks. T1 relaxation times in apparently normal white matter correlated with certain indices of cognitive impairment. In developing a model to explain the pathogenesis of intellectual and emotional change in MS, the interaction of organic, psychological, and social factors needs to be emphasised. PMID- 1431950 TI - Multiple sclerosis in the Cambridge health district of east Anglia. AB - A survey of multiple sclerosis (MS) in the Cambridge Health District has identified 374 cases in a population of 288,410, giving a prevalence of 130 per 100,000. A total of 322 cases (86%) had either clinically definite or probable multiple sclerosis on 1 July 1990 (112 per 100,000) and 52 cases (14%) had suspected multiple sclerosis (18 per 100,000.) The incidence during 1989-91 was 5.94 per 100,000 per year. The prevalence figure is higher than in recent surveys from other southern parts of the United Kingdom, but correction for the age and sex characteristics of the at risk population eliminates these differences. The overall prevalence of multiple sclerosis is probably between 108 and 120 per 100,000 in the southern United Kingdom. PMID- 1431951 TI - Familial multiple sclerosis: MRI findings in clinically affected and unaffected siblings. AB - Subclinical demyelinating lesions may occur in the brains of asymptomatic individuals, and the first-degree relatives of multiple sclerosis (MS) patients are at particular risk. Clinical and MRI examinations were performed in nine sibships from families with two or more cases of MS. These included 14 patients with clinically definite MS, three patients with clinically probable MS, and 27 asymptomatic siblings. Systematic criteria were applied to MRI interpretations to increase their specificity for MS. Thirteen (76%) of the 17 patients with MS showed lesions suggesting MS. Lesions were also found in six (38%) of the 16 asymptomatic siblings under age 50 and in eight (73%) of the 11 over age 50. Judged by stringent criteria, the lesions of only three (11%) of the 27 asymptomatic siblings were considered to be due to demyelination. The results demonstrate the occurrence of subclinical demyelination in asymptomatic siblings of MS patients and stress the importance of clinical follow up and MRI studies of the first-degree relatives when classifying them as healthy in family studies. PMID- 1431952 TI - Postictal switch in blood flow distribution and temporal lobe seizures. AB - The ictal increase of regional cerebral blood flow has yet to be fully utilised in the investigation of focal seizures. Although single photon emission tomography (SPECT) is being increasingly used in the localisation of epileptic foci, the evolution and time courses of the peri-ictal perfusion changes have yet to be clarified. We performed serial SPECT studies in the interictal, ictal and immediate postictal states in 12 patients with refractory temporal lobe epilepsy to define the patterns and duration of peri-ictal cerebral blood flow changes. Visual analysis showed a constant pattern of unilateral global increases in temporal lobe perfusion during seizures which suddenly switched to a pattern of relative mesial temporal (hippocampal) hyperperfusion and lateral temporal hypoperfusion in the immediate postictal period. Quantitative analysis confirmed the visual assessment. Lateral temporal cortex ictal/normal side to side ratios were increased by mean 35.1% (95% confidence interval 21.8% to 48.4%) more in the ictal studies than in the interictal studies and mesial temporal cortex ratios increased by mean 30.8% (22.4% to 39.2%). In the postictal state, however, lateral temporal ratios were reduced by mean 7.7% (-15.8% to 0.4%) compared with interictal values, whereas mesial temporal perfusion was maintained compared with the interictal studies. These observations provide critical information for interpreting scans which can be used in the localisation of epileptic foci. This postictal switch in blood flow patterns may reflect the underlying metabolic processes of neuronal activation and recovery and have implications for understanding the neurobiology of human epileptic seizures. PMID- 1431953 TI - Central nervous system lesions in von Hippel-Lindau syndrome. AB - CNS manifestations were studied in 97 gene carriers of von Hippel-Lindau syndrome (HLS). Haemangioblastomas of the CNS were found in 43 patients (44%), 23 females and 20 males. The mean age at diagnosis was 39 years (12-73 years). A total of 93 haemangioblastomas were detected of which 74% were intracranial and 26% were located in the spinal cord; 75% were predominantly cystic and 25% presented as solid lesions. Multiple lesions were found in 42% of HLS-associated haemangioblastomas, but in none of 51 patients with CNS haemangioblastoma without HLS. Haemangioblastoma was the cause of death in 82% of patients with HLS. Although microsurgery has considerably improved post-operative results, multifocal tumour development and recurrence remain a serious problem in the clinical management of HLS gene carriers. PMID- 1431954 TI - The anatomy lesson of Dr Joan Deyman, by Rembrandt (1606-69). PMID- 1431955 TI - Neurogenic effects on the palatopharyngeal muscle in patients with obstructive sleep apnoea: a muscle biopsy study. AB - Muscle biopsies from the palatopharyngeal muscle of eight patients with obstructive sleep apnoea were performed during uvulopalatopharyngoplasty. Control biopsies were performed during tonsillectomy in seven control patients with no history of symptoms suggesting obstructive sleep apnoea. The diagnosis was based on the patient's history and a whole night recording of arterial oxygen saturation and respiration movements. The mean number of oxygen desaturations > or = 4% per sleeping hour was 39 (range 7-80) in patients with obstructive sleep apnoea. In the control patients the occurrence of muscle fibre type and size relation between type I and type II fibres were comparable to what is found in the quadriceps femoris muscle, but the mean size of the fibres was < 25% of what is found in limb muscles. All biopsies from patients with obstructive sleep apnoea showed abnormalities. Atrophy with a fascicular distribution, increased number of angulated atrophic fibres, a twin or multiple peak distribution of the fibre size spectra, and an abnormal distribution of fibre types in many muscle fascicles corresponding to "type grouping" all points to a neurogenic alteration. This neurogenic lesion may be a primary phenomenon or secondary to the trauma of repetitive and prolonged stretching of the pharyngeal structures during apnoeas. A disturbance of the function of the dilating muscles of the upper airway may be important in causing the abnormal airway collapse seen in obstructive sleep apnoea. PMID- 1431956 TI - Lesions of basal ganglia due to disulfiram neurotoxicity. AB - Three cases of disulfiram induced Parkinsonism and frontal lobe-like syndrome associated with bilateral lesions of the lentiform nuclei on CT scan are reported. Symptoms developed either after an acute high dose of disulfiram (one case) or after several days to weeks of disulfiram treatment (two cases) and persisted over several years in two patients. These observations suggest that basal ganglia are one of the major targets of disulfiram neurotoxicity. The mechanisms of the lesions of basal ganglia may involve carbon disulfide toxicity. PMID- 1431957 TI - Thalamocortical diaschisis: positron emission tomography in humans. AB - To investigate further the relations between cortical energy metabolism and neuropsychological impairment after unilateral thalamic lesion, 55 patients underwent positron emission tomography studies of either cortical oxygen consumption or glucose utilisation, including eight repeat studies, at times ranging from 4 days to 98 months after the onset of the lesion [stroke (n = 44) or stereotaxic VL-Vim thalamotomy performed for movement disorders (n = 11)]. Patients with thalamotomy were also studied preoperatively and the surgery induced a significant fall in cortical metabolism on both sides (more so ipsilaterally); post-operatively the magnitude of the ipsilateral cortex hypometabolism was positively correlated to the severity of global neuropsychological impairment; similar but less significant findings were obtained for the ipsilateral/contralateral cortical metabolic asymmetry. With respect to the whole patient sample, the cortical metabolic asymmetry was initially pronounced, with subsequent monoexponential recovery, in the cognitively impaired study group, but it was only mild and showed no meaningful trend for recovery in the cognitively unaffected study group; yet even soon (< 3 months) after thalamic lesion there was a noticeable overlap of individual asymmetry values among the two study groups. These results lend further support to the view that the neuropsychological impairment that frequently follows unilateral thalamic lesions is reflected in a depression of synaptic activity in both the overlying and the contralateral cerebral cortices. For individual patients, this study also illustrates the potentially misleading nature of the measured cortical metabolic asymmetry with respect to neuropsychological status, especially at late times after lesion, in part because side to side metabolic ratios do not reflect bilateral changes. PMID- 1431958 TI - Cerebral symptoms after whiplash injury of the neck: a prospective clinical and neuropsychological study of whiplash injury. AB - Twenty one unselected patients with an acute whiplash injury of the neck had neurological and neuropsychological assessment, cervical x rays, EEG, BAEP, MRI, and an otoneurological examination within two weeks of the injury. Subjectively, 13 patients reported concentration deficits, 18 reported sleep disturbances, 9 had symptoms of depression, and 7 female patients told of menstrual irregularities. Neuropsychological examination revealed significantly lower performance in tests related to attention and concentration compared to sex, age and educational matched control subjects. Otoneurological examination showed abnormalities in 9 of 17 whiplash subjects. EEG showed questionable changes in 8 of 18 recordings. MRI and BAEP were normal in all patients. Repeat neuropsychological testing in 15 patients at three months showed that attention deficits had improved but were still shown in 12 of 14 and the concentration deficits in 8 of 13 patients. At one year all patients had returned to work, 16 to full and 5 to part time employment. In 4, cognitive dysfunction remained the only significant problem. These findings are discussed as being compatible with possible damage to basal frontal and upper brain stem structures after whiplash injury of the neck. PMID- 1431959 TI - Delayed radiation necrosis of the central nervous system in patients irradiated for pituitary tumours. AB - Four cases of delayed radiation necrosis involving the CNS were found in a group of 46 patients irradiated for pituitary tumours over a six year period. This occurred in three of 11 patients with Cushing's disease representing an incidence of 27% in this group. There were no cases among 11 patients with acromegaly or among seven with prolactinomas. One case (6%) was found in the 17 patients with chromophobe adenomas. Standard doses of radiation were delivered to these patients and the findings support suggestions that the metabolic disturbances of Cushing's disease may reduce tolerance to radiation. Our results and a literature review indicate that if radiotherapy is used to treat Cushing's disease, the total dose should be less than 50 Gy at 2 Gy per day fractionation. PMID- 1431960 TI - Heterogeneity in Alzheimer's disease: progression rate segregated by distinct neuropsychological and cerebral metabolic profiles. AB - In an attempt to define possible subgroups of Alzheimer's disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimer's disease. PMID- 1431961 TI - SPECT findings in Parkinson's disease associated with dementia. AB - Dementia in Parkinson's disease is thought to be attributable not only to subcortical lesions but also to cortical alterations, especially frontal lobe dysfunction. To evaluate cortical function, the regional cerebral blood flow (rCBF) was estimated of 13 demented and 13 non-demented age matched patients with Parkinson's disease compared with that of 10 age matched controls using I-123 iodoamphetamine single photon emission tomography (IMP-SPECT). The rCBF of the nondemented Parkinson's patients showed no significant differences from that of the control subjects. In the demented patients, the bilateral frontal and parietal and left temporal regional blood flow was significantly less than in the controls. Four demented patients showed isolated frontal hypoperfusion, 8 showed fronto-parietal hypoperfusion, and 1 showed isolated parietal hypoperfusion. Frontal hypoperfusion was therefore present in 12 of the 13 demented patients, and this finding agrees with the frontal lobe dysfunction hypothesis. Parietal rCBF had a significant positive correlation with cortical functions such as calculation and language ability in the MMSE scores. The parietal and temporal reduction in rCBF probably reflects the presence of Alzheimer pathology, cortical Lewy body disease, or both. PMID- 1431962 TI - Focal transcranial magnetic stimulation and response bias in a forced-choice task. AB - The effects of transcranial magnetic stimulation were studied on the performance of a warned, forced-choice response time task by normal adults. The task consisted of extension of the index finger in response to the click produced by the discharge of the magnetic coil (go-signal). The subjects were asked to choose the right or left finger only after the go-signal was delivered. Single magnetic stimuli were delivered to the prefrontal or motor area, and in the control situation, away from the head. Magnetic stimulation affected hand preference only when it was delivered to the motor area. With stimulation of this area, subjects more often chose the hand contralateral to the site stimulated with response times that were mainly less than 200 ms. With longer response times (between 200 and 1100 ms), magnetic stimulation had no effect on hand preference regardless of the site stimulated. Stimulation of prefrontal areas yielded results similar to the control situation. These results suggest that response bias in this paradigm is caused by an effect of magnetic stimulation on neural structures within, or closely related to, the motor areas of the brain. Although the response bias was clear and predictable, the subjects were unaware of its existence. It is possible to influence endogenous processes of movement preparation externally without disrupting the conscious perception of volition. PMID- 1431963 TI - Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. AB - Magnetic resonance imaging (MRI) has shown a great reduction in medial temporal lobe and hippocampal volume of patients with Alzheimer's disease as compared to controls. Quantitative volumetric measurements are not yet available for routine clinical use. We investigated whether visual assessment of medial temporal lobe atrophy (MTA) on plain MRI films could distinguish patients with Alzheimer's disease (n = 21) from age matched controls (n = 21). The degree of MTA was ascertained with a ranking procedure and validated by linear measurements of the medial temporal lobe including the hippocampal formation and surrounding spaces occupied by cerebrospinal fluid. Patients with Alzheimer's disease showed a significantly higher degree of subjectively assessed MTA than controls (p = 0.0005). Linear measurements correlated highly with subjective assessment of MTA and also showed significant differences between groups. Ventricular indices did not differ significantly between groups. In Alzheimer's disease patients the degree of MTA correlated significantly with scores on the mini-mental state examination and memory tests, but poorly with mental speed tests. This study shows that MTA may be assessed quickly and easily with plain MRI films. MTA shown on MRI strongly supports the clinical diagnosis of Alzheimer's disease, is related to memory function, and seems to occur earlier in the disease process than does generalised brain atrophy. PMID- 1431964 TI - Hospital arrival time after onset of stroke. AB - To estimate the proportion of patients with stroke likely to be eligible for a trial of anticoagulant treatment for acute ischaemic stroke, the interval between onset of symptoms and arrival at hospital was analysed prospectively. Of 773 patients with stroke admitted in one year, 63% arrived at hospital within 12 hours, 76% within 24 hours, and 85% within 48 hours of ictus. The arrival time varied significantly with stroke subtype. Patients with intracerebral haemorrhage tended to arrive earlier than those with cerebral infarct, who arrived sooner than those with lacunar infarct. The results suggest that about half of all patients with ischaemic stroke in Hong Kong would present within 12 hours of ictus, in time for inclusion in a therapeutic trial. PMID- 1431965 TI - Delayed postexertional headache, intracranial hypotension and racket sports. PMID- 1431966 TI - Chronic inflammatory polyneuropathy associated with nephropathy and antifactor VIII antibody: improvement with intravenous immunoglobulin. PMID- 1431967 TI - Acute stage Bell's palsy and narrowing of the palpebral fissure caused by drooping of the eyebrow and the upper eyelid. PMID- 1431968 TI - Familial recurrent cranial nerve palsy. PMID- 1431969 TI - Transient amnesia heralding brain stem infarction. PMID- 1431970 TI - MRI in monitoring the treatment of multiple sclerosis: concerted action guidelines. PMID- 1431971 TI - The prognosis of primary intracerebral tumours presenting with epilepsy: the outcome of medical and surgical management. PMID- 1431972 TI - Extracranial vertebral artery dissection. PMID- 1431973 TI - Late onset globoid cell leukodystrophy. PMID- 1431974 TI - Aseptic meningitis associated with high dose intravenous immunoglobulin therapy. PMID- 1431975 TI - (99mTc)-HM-PAO SPECT and dementia in Parkinson's disease. PMID- 1431976 TI - The brain in schizophrenia. PMID- 1431977 TI - Angiostrongylus cantonensis abscess in the brain; what do we learn? PMID- 1431978 TI - Hand-held myometry. PMID- 1431979 TI - Paroxysmal kinesigenic choreoathetosis. PMID- 1431980 TI - Actively and passively evoked P3 latency of event-related potentials in Parkinson's disease. AB - Event-related potentials (ERPs) generated during the performance of visual discrimination tasks were studied in 31 patients with Parkinson's disease, 9 patients with Alzheimer's disease, and 37 normal control subjects. Actively and passively evoked P3 components (P3b and P3a) were respectively identified as the components of the P3 response to infrequent target stimuli and infrequent non target stimuli. Both the P3a and P3b latencies were significantly prolonged by normal aging. Nine of the Parkinson's disease patients showed a P3b latency above the 95% confidence limit of the age-adjusted regression line based on the normal controls, while only on patient had a prolonged P3a latency. In 6 patients with demented Parkinson's disease, the P3b latency was significantly longer than in 15 age-equivalent normal subjects, although no significant difference was found in the P3a latency. On the other hand, patients with Alzheimer's disease showed significant prolongation of both the P3a and P3b latencies compared to the normal controls. Furthermore, there was a significant difference in P3a latency between patients with demented Parkinson's disease and those with Alzheimer's disease. These results suggest that the automatic processing stage associated with P3a may be less impaired than the attention-controlled processing reflected by P3b in patients with Parkinson's disease, and also indicate that there may be some differences in the changes of cognitive processing caused by Parkinson's disease and Alzheimer's disease. PMID- 1431981 TI - The epidemiology of multiple sclerosis: the Iceland model. Onset-adjusted prevalence rate and other methodological considerations. AB - The epidemiology of multiple sclerosis (MS) is characterized by the fact that there is an uneven distribution of the disease throughout the world. The two most commonly used indices of its frequency are the incidence and prevalence rates. The incidence rate reflects, to a great extent, the influence of environmental factors in triggering the clinical manifestations of the disease, if it is based upon the actual date of the initiation of symptoms, rather than the date of diagnosis. The prevalence rate is currently based on the date of diagnosis and includes all MS patients who are alive on a particular date, without regard to their ethnic origin, the site and the duration of residence or any other factors that may have influenced the acquisition of the disease. We propose that in order to make the concept of the prevalence rate possibly more meaningful, the term should refer, retrospectively, to all patients whose symptoms eventually led to the diagnosis of MS, even though the diagnosis was not yet established on an earlier prevalence day. In addition, only patients of the same ethnic background who have spent their prepuberal years in the geographical area under study should be included. We are calling this measure the onset-adjusted prevalence rate. Another problem encountered in epidemiological studies of MS relates to the common practice of adjusting prevalence data obtained for age and sex in one area to what is referred to as a "standard" American (or world) population, groups of great ethnic and age diversity. It is also curious that in many studies the bases for comparison of populations are census data obtained many years previously. We suggest that age and sex adjustment should be applied only to similar ethnic groups born and raised under different environmental conditions. We believe that data obtained by calculating an onset-adjusted prevalence rate restricted to a homogeneous group of patients sharing the same environment during the prepuberal years may provide valuable etiological clues. PMID- 1431982 TI - Cerebral microcirculatory changes during and following transient ventricular tachycardia in cats. AB - Although reduced cerebral perfusion is believed to be the cause of syncope due to cardiac arrhythmias, investigations on the cerebral microcirculation during cardiac arrhythmias have been rare. We therefore studied the effects of transient ventricular tachycardia on the local cerebral blood volume and blood flow. Experimental ventricular tachycardia was induced in cats by electrically stimulating the ventricle of the heart at a rate of 300/min for 1 min. Using our photoelectric method, the local cerebral blood volume, mean transit time of blood, and cerebral blood flow in the parieto-temporal region were measured during and for 3 h after ventricular tachycardia. Transient ventricular tachycardia of as short as 1 min caused cerebral ischemia with a blood flow reduction of approximately 30%. This was considered to be due to reduced blood pressure plus transient autonomic dysfunction, or dysautoregulation, during the ventricular tachycardia. Mild and transient reactive hyperemia occurred immediately after termination of the dysrhythmia, but continuous reductions of cerebral blood flow were observed thereafter for 3 h. This delayed hypoperfusion is attributable to either vasoconstriction of the large resistance vessels or changes in the hemorheological properties of the blood caused by cerebral ischemia. Ventricular tachycardia of the type reported has significant and long lasting effects on the cerebral microcirculation. PMID- 1431983 TI - Autopsy report of primary CNS B-cell lymphoma indistinguishable from multiple sclerosis: diagnosis with the immunoglobulin gene rearrangements analysis. AB - We report a case of primary CNS B-cell lymphoma indistinguishable from multiple sclerosis (MS). MRI of the head showed the spontaneous disappearance of the white matter lesions and the progressive cerebral atrophy. The brain biopsy failed to make a diagnosis of CNS lymphoma but rather suggested MS. Although the primary CNS lymphoma was suspected at autopsy, the immunohistochemical study showed the CNS-infiltrating lymphoid cells comprising both T-cells and B-cells. Analysis of the immunoglobulin and T-cell receptor gene rearrangements first provided evidence of primary CNS B-cell lymphoma. PMID- 1431984 TI - Corticospinal conduction studied with magnetic double stimulation in the intact human. AB - A group of 8 healthy normal subjects (24-36 years old, mean age 29 years) were investigated. Transcranial magnetic double stimulation of the motor cortex was carried out at different interstimulus intervals. With both stimuli suprathreshold, an attenuation of the test response was found at interstimulus intervals of less than 200 msec (target relaxed or contracted). The manifestation of this attenuation correlated with central signs in 31 patients with multiple sclerosis. This phenomenon is (at least at longer intervals) probably not a result of the refractory spinal motoneuron pool, but of a supraspinal inhibitory mechanism or lack of corticospinal drive caused otherwise. At interstimulus intervals between 10 and 30 msec, the test response increases significantly (magnetic double stimulation 10% suprathreshold, target relaxed). This result is also seen with voluntary muscle contraction and with vibration applied to a relaxed target muscle. The facilitatory effect is probably caused by slowly conducted corticospinal volleys enabling summation, with descending impulses generated by the test stimulus. With the conditioning stimulus subthreshold and target muscle relaxed an intracortical inhibition of the test response could be confirmed at short interstimulus intervals. PMID- 1431985 TI - An insert mutation in the chromosome 20 amyloid precursor gene in a Gerstmann Straussler-Scheinker family. AB - We report the finding of an insert mutation in the chromosome 20 amyloid precursor gene in a family with neuropathologically-verified, experimentally transmitted Gerstmann-Straussler-Scheinker syndrome (GSS). The insert consisted of 8 extra copies of a repeating octapeptide coding sequence in the region between codons 51 and 91; it was identified in the proband and a presently unaffected at-risk niece by full sequencing of the open reading frame, and was visualized electrophoretically in the proband and 6 of 12 at-risk relatives. Although affected members in this French-Breton family have shown a variety of clinical profiles, including durations of illness that ranged from 3 months to 13 years, all autopsied cases (including the patient with the shortest illness) have had the distinctive multicentric amyloid plaques that define GSS as a nosologic entity. PMID- 1431986 TI - Increased striatal 18F-dopa uptake and normal glucose metabolism in idiopathic dystonia syndrome. AB - Striatal 18F-Dopa uptake and glucose metabolism were studied by positron emission tomography with 6-L-[18F]fluorodopa and [18F]fluorodeoxyglucose, respectively, in 8 patients with idiopathic dystonia. Patients with abnormal findings on the brain CT and MRI were excluded from this study. The clinical diagnosis consisted of torsion dystonia in 3 patients, focal dystonia limited in the arm in 3 and cervical dystonia (spasmodic torticollis) in 2. The 18F-Dopa uptake, corrected by nonspecific retention in the cerebellum, at 120 min post-administration was evaluated, and increased 18F-Dopa uptake in the putamen and in the caudate head was observed in the patients with idiopathic dystonia compared to the normal controls. The striatal glucose metabolism in the patients with idiopathic dystonia showed no difference with the normal controls. These findings suggest that pathogenetic mechanism of idiopathic dystonia involves increased presynaptic activity of the dopaminergic system in the striatum. PMID- 1431987 TI - Endoneurial blood supply to peripheral nerves is not uniform. AB - Peripheral nerves are not uniformly susceptible to the effects of ischemia in human and experimental ischemic neuropathies. Since endoneurial blood flow is directly proportional to the number of endoneurial capillaries, we studied endoneurial capillary density at multiple levels of the peripheral nerves of normal rats. Capillary density was lowest in the sciatic and proximal tibial nerves and significantly higher in dorsal and ventral roots and distal tibial and plantar nerves. Endoneurial capillary density corresponds to the hierarchy of susceptibility to ischemic nerve damage in human and experimental ischemic neuropathies. These findings suggest that susceptibility of peripheral nerves to ischemia is determined, at least in part, by the density of endoneurial capillaries. PMID- 1431988 TI - Regeneration after free muscle grafting in normal and dystrophic (mdx) mice. AB - Soleus muscles from C57BL/10 and mdx mice were isotransplanted to induce a cycle of degeneration/regeneration. Sixty days post-surgery, transplanted and contralateral soleus muscles were removed for mechanical and biochemical analyses. The regeneration which occurs after transplantation, induces in both mdx and C57BL/10 soleus muscles a decrease in maximal isometric force, together with an increase of the velocity of contraction. This increase in velocity is accompanied by the expression of typically fast-type myosin heavy chains. Thus degeneration/regeneration of both mdx and normal mice are very similar, causing a shift towards physiologically 'faster' muscle. Previous physiological and biochemical studies of mdx muscles have shown that mdx muscle is shifted towards 'slower' muscle compared to normal mice. One explanation of these findings was that the degeneration/regeneration cycles inherent in dystrophin-deficient mdx muscle causes a shift towards 'slow'. Our results argue against this hypothesis: degeneration/regeneration in both normal and mdx mice causes a shift towards 'fast'. PMID- 1431990 TI - Use of single strand conformation polymorphism analysis to detect point mutations in human mitochondrial DNA. AB - Myoclonus epilepsy with ragged-red fibers (MERRF) has been shown to be associated with a specific point mutation at the nucleotide 8344 in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). We screened 6 patients with clinically diagnosed MERRF and 1 patient with ocular myopathy for point mutations in the tRNA(Lys) gene, using single strand conformation polymorphism (SSCP) analysis, which can detect even a 1-basepair difference between 2 DNA sequences. Using SSCP and consequent DNA sequencing, we identified the known MERRF mutation in 4 out of 6 MERRF patients, as well as in 1 patient with a new clinical phenotype associated with this mutation: progressive external ophthalmoplegia, muscle weakness and a lipoma, but no myoclonus or epilepsy. Two of the patients with clinical MERRF had neither the MERRF-mutation nor any other mutations in the tRNA(Lys) gene. Using SSCP analysis, we also detected a new polymorphism in 1 patient. Thus, SSCP analysis can be applied to search effectively and rapidly for point mutations or polymorphisms in mitochondrial DNA. PMID- 1431989 TI - Dilating cardiomyopathy as the expression of Xp21 Becker type muscular dystrophy. AB - A 35-year-old man with severe progressive dilating cardiomyopathy and no clinical signs of muscle disease underwent muscular investigations because of markedly increased serum creatine kinase. Muscle biopsy demonstrated Becker type muscular dystrophy with dystrophin of low molecular weight. Genetic analysis showed a deletion spanning from exon 45 to exon 46 in the Xp21 region. Xp21 Becker type muscular dystrophy must be considered in the differential diagnosis of dilating cardiomyopathy. PMID- 1431991 TI - Intracerebral haemorrhage in Sneddon's syndrome. PMID- 1431992 TI - Benign paroxysmal positional vertigo (BPPV) or bubble provoked positional vertigo? PMID- 1431993 TI - Reply to Arnason: "Multiple sclerosis: additional thoughts. PMID- 1431994 TI - Distribution of calbindin and parvalbumin in the developing somatosensory cortex and its primordium in the rat: an immunocytochemical study. AB - Immunocytochemical techniques were used to analyze the distribution of the calcium-binding proteins calbindin and parvalbumin during the pre- and postnatal development of the rat somatosensory cortex. Calbindin occurs in most early differentiated neurons that form the primordial plexiform layer at embryonic day 14. This expression in transient; during the perinatal period, calbindin becomes immunologically undetectable within the structures derived from the primordial plexiform layer, i.e., the prospective layers I and VIb. Immunoreactive neurons are also absent from adult layers I and VIb. Calbindin is also detected in a second population of neurons which, from embryonic day 18 onwards, distributes diffusely within the cortical plate. Some neurons of this population show morphological traits of immaturity, while others show complete dendritic arborization. The definitive pattern of distribution of calbindin-immunoreactive neurons is achieved by postnatal day 22. Infragranular layers contain intensely immunoreactive cells whose numerical density decreases during postnatal development, whereas in supragranular layers similar neurons are interspersed among numerous faintly-stained neurons. Parvalbumin is detected for the first time at postnatal day 6, within a small group of neurons located in cortical layer V, and extends afterwards through the whole thickness of the cerebral cortex. At this same postnatal stage, groups of immunoreactive puncta are also found in layer IV of the somatosensory cortex; these puncta increase in density progressively and, at embryonic day 13, immunoreactive cells appear also grouped at this level. At this postnatal age, parvalbumin immunostaining delineates the somatosensory map in cortical layer IV. From this stage to adulthood, the number of immunoreactive neurons increases in the whole thickness of the somatosensory cortex. Barrels in layer IV become less distinct as immunoreactive cells and processes invade the septa. Layer IV in the adult somatosensory cortex appears more densely populated by parvalbumin immunoreactive neurons and puncta than in the surrounding areas. PMID- 1431996 TI - Ultrastructural localization of calcium in mechanoreceptors of the oral mucosa. AB - Cytochemical localization of Ca2+ in Meissner corpuscles and Merkel cell-neurite complexes in the palatine mucosa of the Mongolian gerbil was studied by a combined oxalate antimonate-microwave irradiation procedure. The reaction products obtained were identified as calcium antimonate by EGTA solubility and X ray microanalysis. Meissner corpuscles in the normal palatine rugae could be roughly classified into three types by amount and localization of Ca2+. Type I corpuscles were characterized by a high Ca2+ content in both the terminal axoplasm and caveolae of the lamellar plates, type II, by a low Ca2+ content in the terminal axoplasm and a high Ca2+ content in the lamellar cytoplasm. Type III corpuscles showed intermediate characteristics. Palatine rugae stimulated mechanically during fixation contained an increased number of type I corpuscles. On the other hand, two patterns were distinguished in the distribution of Ca2+ in Merkel cells in palatine rugae fixed under normal conditions. One showed abundant Ca2+ dispersed throughout the cell, while in the other, Ca2+ was specifically localized in the Golgi apparatus and mitochondria. Similar distribution patterns also were observed in palatine rugae that had received mechanical stimulus during fixation. Axon terminals of most Merkel cell-neurite complexes in normal palatine rugae were poor in axoplasmic Ca2+, whereas those in most Merkel cell-neurite complexes in mechanically stimulated palatine rugae contained abundant Ca2+ in their axoplasm. PMID- 1431995 TI - The distribution of clones of neurons in the rat somatosensory cortex. AB - We have labelled clones of neurons in the cerebral cortex of rats by introducing a retroviral vector, called BAG, into the cerebral vesicles of embryos in utero. BAG encodes the enzyme beta-galactosidase, which acts as a histochemical marker for the subsequent identification of clones derived from infected precursor cells. We have studied the distribution of neuronal clones in the rat somatosensory cortex, and have asked whether clonally-related neurons were dispersed randomly. We have discovered that they are not. Rather, clones disperse predominantly such that the earliest progeny of ventricular zone cell are found posterolateral to later generated cells. This distribution fits with what would be expected were neurons dispersed passively in accordance with the lateral to medial cortical neurogenic gradient. PMID- 1431997 TI - Influence of an endogenous lectin substrate on cultured dorsal root ganglion cells. AB - Dorsal root ganglion neurons normally contain a 14,500 molecular weight lactose binding lectin, designated L-14. Although this lectin is developmentally regulated, and is localized to specific neurons as well as to specific areas of the rat spinal cord, its function in the nervous system is not known. In an effort to study the possible role of this lectin on peripheral neurons, they were dissociated and grown on substrates consisting of either L-14 or laminin, a molecule known to support neurite outgrowth. In contrast to the random distribution and fine neurites displayed by neurons on laminin, those growing on L-14 formed large aggregates with highly fasciculated neurite bundles. Experiments using plant lectins with sugar-binding specificity similar to that of L-14, as well as another endogenous rat lectin not present in neurons, resulted in essentially no neuronal attachment or neurite outgrowth. In addition, the effects induced by L-14 were not blocked by high concentrations of competing sugars, suggesting that it interacts with neurons by a domain distinct from its carbohydrate-binding site. PMID- 1431998 TI - Topography of opsin within disk and plasma membranes revealed by a rapid-freeze deep-etch technique. AB - Rod outer segments in fresh rat retinas were examined by a rapid-freeze, deep etch technique to explore how membrane proteins are organized at the macromolecular level. Cross-fractures revealed that intradiscal membranes are adherent to each other except at the rim. When an isolated fresh retina was incubated in a hypotonic solution for a few minutes, the interdiscal space was expanded and the cytoplasmic surface of the disk membrane was found to be covered with protrusions except at the rim. A few particles were scattered among the protrusions and were attached to the cytoplasmic surface. Since the distribution density of the cytoplasmic surface protrusions was similar to that of the P-face particles, which are known to reflect opsins, the protrusions were considered to be portions of opsins extending into the cytoplasm. The intradiscal surfaces in chemically-fixed retinas were rather smooth and were labelled with anti-opsin antibodies and wheat germ agglutinin. The true surfaces of the plasma membrane were found to be similar in fine structure to those of the disk. A model of the macromolecular organization of rod outer segments is proposed on the basis of these observations. The model shows apposed opsins within a disk membrane adhering to one another except at the rim. These opsins, as well as those in the plasma membrane, are minimally exposed to the extracellular surface, but protrude deeply into the cytoplasm. PMID- 1431999 TI - Electron microscopic immunocytochemistry of GAP-43 within proximal and chronically denervated distal stumps of transected peripheral nerve. AB - Growth-associated protein, GAP-43 was initially described as a neuron-specific molecule thought to play a critical role in axonal growth and regeneration. However, it is also expressed in vitro in certain CNS glia, Schwann cell precursors and non-myelinating Schwann cells. In this paper, we report the subcellular localization of GAP-43 in vivo in chronically-denervated Schwann cells in the distal stumps of previously transected rat sciatic nerve. We have used a progressive lowering of temperature method combined with the non-polar acrylic resin Lowicryl HM20 and a post-embedding labelling regime to visualize the distribution of GAP-43, S-100 (marker for Schwann cells), RT97 and NF68 (markers for different subunits of the neurofilament molecule). We report that (1) the smallest calibre regrowing axons were GAP-43-positive, sometimes NF68 positive but always RT97-negative; (2) regenerating myelinated axons and larger unmyelinated axons (> 0.7 microns diameter) were NF68-positive, RT97-positive but GAP-43-negative; (3) cytoplasmic processes within Schwann cell basal lamina tubes in the distal stumps were S-100-positive, GAP-43-positive but RT97- and NF68 negative. The similar localization of GAP-43 within regrowing axons and denervated Schwann cells suggests that GAP-43 may function similarly in both situations, and may thus be involved in motility and/or elongation of axons and Schwann cells during regeneration. PMID- 1432000 TI - "Rainbow Reviews". V: Recent publications of the National Center for Health Statistics. PMID- 1432001 TI - A comparative contrast of clinimetric and psychometric methods for constructing indexes and rating scales. PMID- 1432002 TI - An assessment of the usefulness of demographic data provided by surrogate respondents in a case-control study of Parkinson's disease. AB - This study, based upon data from 40 non-demented Parkinson's disease cases and 101 community controls, and similar data provided by either the spouse (n = 110) or an adult child (n = 31) of each index subject, attempted to assess the usefulness of various demographic data provided by the surrogate respondents for the index subjects. The data were collected by personal interview using a structured questionnaire specifically developed for this study. Ninety-one percent of the index subjects and their surrogates provided information on the annual family income and 98% provided other demographic information. The analysis was done by three groups: the case-surrogates, the control-surrogates and the combined index subject-surrogates, and within each group by the two types of surrogates for the index subjects: the spouse vs adult child. The overall percent agreement between the index subjects and their surrogates varied from moderate for annual family income (54.1%), to good for educational level (61.6%) and to excellent for ethnic origin (82.6%), for age +/- 1 year (97.9%) and for marital status (100.0%). No significant differences in agreement were found for any of these demographic variables either between the case-surrogate group and the control-surrogate group, or between the spouse surrogates and the child surrogates. These findings suggest that spouses and adult children can provide valid information and are equally reliable informants concerning the demographic characteristics of index subjects in a case-control study of Parkinson's disease and, possibly, of other diseases. PMID- 1432003 TI - Diagnostic tools in Lyme borreliosis: clinical history compared with serology. AB - The occurrence of a history of clinical Lyme borreliosis and the prevalence of positive antibodies to Borrelia burgdorferi were studied in 431 Dutch hunters. The majority of the hunters (336 or 78%) did not report any complaints and had no positive IgG antibodies to B. burgdorferi. Sixty-five hunters (15.1%) had no clinical manifestations but did not have positive antibodies to B. burgdorferi. Only 1.9% of the population studied had had past symptoms of definite or probable Lyme borreliosis. Likelihood ratios were high (21.3) for the recognition of erythema migrans, but much lower for tick bites (3.6) or positive IgG Lyme serology (3.5). Clinical history turned out to be a more powerful diagnostic tool than Lyme serology. PMID- 1432004 TI - The logistic modeling of interobserver agreement. AB - An approach to the logistic modeling of interobserver agreement is described that allows for the estimation of a commonly employed measure of agreement. The dependent variable is defined to be 1 if the two raters agree, and 0 otherwise. Covariates may be included in the regression equation in order to obtain adjusted or subgroup-specific estimates of percent agreement. As an empirical example, logistic models were fitted to data from a validation study of the agreement between interview information and physician records on the history of post menopausal estrogen use, from a case-control study of breast cancer conducted on Oahu, Hawaii. Variables found to be related to agreement in previous univariate analyses were examined as covariates in the logistic model. The directly calculated estimates of percent agreement agreed well with the modeled estimates derived from the regression coefficients. Thus, the logistic model may provide a useful alternative to existing methods for the description of interobserver agreement. PMID- 1432005 TI - Using college alumni populations in epidemiologic research: the UNC Alumni Heart Study. AB - The UNC Alumni Heart Study (UNCAHS) is a prospective study of the role of psychosocial factors, in particular hostility, in the development of coronary heart disease. The target population is composed of persons who completed the Minnesota Multiphasic Personality Inventory while attending the University of North Carolina in the mid-1960s. Logistic regression analyses were used to determine whether hostility, demographic and other variables were significant determinants of the subjects' locatability and participation. It was found that MMPI hostility scores at initial testing were unrelated to either potential or actual locatability or participation. Thus there is no evidence that hostility is the source of selection bias in the UNCAHS. Selection into the study was predicted by age, sex, degree status and variables concerned with the conditions under which the MMPI was administered. It is concluded that follow-up studies of college cohorts may have study-specific sources of selection bias. PMID- 1432006 TI - Meta-analysis adjusting for compliance: the example of screening for breast cancer. AB - Randomized controlled trials are usually analysed by the group to which the patient was randomized, i.e. by "intention-to-treat", regardless of the degree of compliance. However, the "explanatory" effect, i.e. the effect that would occur if we had 100% compliance, is often of interest. This "explanatory" effect is diluted by poor compliance, and hence meta-analyses should ideally avoid both the heterogeneity of effect due to variation in compliance rates among studies, and the undeserved weight given to trials with poor compliance. Newcombe's deattenuation method, which adjusts estimates for the degree of compliance, is extended and applied to a meta-analysis of the five reported randomized controlled trials of mammographic screening. Compliance with screening varied across studies: from 61 to 93% assigned to screening had one or more mammograms. The adjusted estimate of the reduction in breast cancer mortality at 9 years follow-up is 0.37 (95% confidence interval: 0.21, 0.49). PMID- 1432007 TI - Intrauterine growth retardation and blood pressure at age seven and eighteen. AB - The association between intrauterine growth retardation and blood pressure in middle childhood and early adulthood was examined. At age 7, after adjusting for sex and weight, the differences between normal children and those who had experienced intrauterine growth delay were 0.9 mmHg (95% CI -0.1 to 2.2) for systolic and 0 mmHg (-1.7 to 2.0) for diastolic blood pressure respectively. The differences between the blood pressures of intrauterine growth retarded infants with an appropriate ponderal index and those with a low ponderal index were 4.4 mmHg (-0.9 to 7.9) for systolic, and 3.8 mmHg (0.2 to 7.3) for diastolic blood pressure respectively. At age 18 the differences were much less pronounced. The association between blood pressure and the placental weight was also examined. The evidence from this sample lends weak support to the findings of other studies which suggest that there is an association between factors occurring before or around the time of birth and blood pressure in later life. PMID- 1432008 TI - Oxygen as a cause of blindness in premature infants: "autopsy" of a decade of errors in clinical epidemiologic research. AB - Several intellectual "autopsies" have recently reviewed errors in clinical epidemiologic studies of causation, such as the original claim that amyl nitrite "poppers" caused AIDS. The current autopsy was done to determine why it took more than a decade--1942 to 1954--to end an iatrogenic epidemic in which high-dose oxygen therapy led to retrolental fibroplasia (RLF) in premature infants, blinding about 10,000 of them. The autopsy revealed a museum of diverse intellectual pathology. When first noted, RLF was regarded as neither a new disease nor a postnatal effect. In early investigations, the ophthalmologists did not establish explicit criteria for diagnosis and confused RLF with malformations previously seen in full-term infants. Because the patients were not referred until months after birth, the ophthalmologists assumed that the lesion, which resembled an embryologic structure, must have occurred prenatally. Other events suggesting a prenatal cause for RLF were its strong statistical associations with fetal anomalies, multiple gestations, and maternal infections. Although these events were also associated with prematurity, it was ignored when the RLF cases were compared with controls who were mainly full-term infants. The postnatal timing of RLF was eventually recognized when investigators did cohort studies in premature infants and found that RLF could develop in eyes that were normal at birth. As the search for a cause turned to events occurring after birth, statistical associations were produced for agents such as light, vitamins, iron, vitamin E deficiency, and hypoadrenalism. Each study had its own methodologic flaws: controls were missing for light; co-maneuvers were ignored for vitamins and iron; objective diagnosis was not used for vitamin E deficiency; and the research on hypoadrenalism contained biases in susceptibility and detection as well as problems of a competing outcome event. When the role of oxygen administration was first considered, the statistical association with RLF was stronger for vitamin- and iron-therapy than for oxygen. In addition, many investigators were dissuaded by contradictory evidence from institutions in which RLF was either absent despite high-dose oxygen or persistent despite reduced dosage. The contradictory evidence was later regarded as erroneous because of unsatisfactory delivery systems for the oxygen or failure to check the actual oxygen concentrations. An alternative explanatory hypothesis, rejecting the role of high-dose and long-duration oxygen, was the idea that RLF was due to "relative hypoxia", produced by overly rapid weaning from oxygen therapy rather than the duration of oxygen treatment itself.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432009 TI - Diagnostic problems with meningococcal disease in general practice. AB - Based on general practitioners' referral letters and hospital records, we made a retrospective analysis of a cohort of 177 consecutive cases of meningococcal disease that occurred during a period of 10 years in the County of North Jutland, Denmark. The analysis concerned diagnostic problems in general practice, prognosis, pre-hospital antibiotic treatment and its effect on subsequent cultures, and degree of obligatory notification. The referring doctor suspected meningococcal disease/central nervous infection in 123 patients (69.5%). Neck stiffness and petechiae were related to a correct referral diagnosis, in contrast to the occurrence of a non-petechial rash. The presence of disseminated intravascular coagulation was associated with the mortality rate, which was 0.062. The therapeutic recommendations of the Danish Health Authorities were followed in only 25 of the 98 patients who fulfilled the criteria for pre hospital parenteral antibiotic treatment. Pre-hospital antibiotic treatment was related to negative culture of spinal fluid or blood. Seven of the 177 patients were not notified according to the rules. Difficulties in pre-hospital diagnosis seem not to influence the lethal course of the disease. PMID- 1432010 TI - Quality of life and functional health of primary care patients. AB - Quality of life and functional health were measured cross-sectionally for 314 adult ambulatory primary care patients in a rural clinic and found to be much better for patients with low severity of illness who required no confinement to home because of health problems, than for patients with high severity of illness who required confinement. Severity of illness was the strongest predictor for patient-reported physical health function and for patient quality of life when assessed by the health provider. Confinement was the strongest predictor for patient quality of life when assessed by the patient. There was very little agreement between patient-assessed and provider-assessed quality of life. Family stress was the strongest predictor of function in terms of mental health, social health, general health, self-esteem, anxiety, and depression. These data suggest that clinicians should direct increased attention to patient-assessed quality of life, patient-reported functional health status, and psychosocial factors such as family stress in an effort to improve medical outcomes. PMID- 1432011 TI - Functional ability of community dwelling elderly. Criterion-related validity of a new measure of functional ability. AB - Criterion-related validity of a new measure of functional ability was conducted according to a causal model based on conceptual models employed in the area of rehabilitative and geriatric medicine. The criteria variables included concurrent diagnosed diseases, global self-rated health, drug consumption and general practitioner (GP) consultations. The measure of functional ability was developed with the intention of achieving a high degree of discrimination among a group of community dwelling elderly. Data were derived from a sample survey of 70-year-old men and women conducted in 1984 in the county of Copenhagen (Denmark). Altogether 366 men and 368 women participated in each of the two phases of the study--a comprehensive medical examination at the county hospital at Glostrup followed by a home visit conducted by an occupational therapist 1-2 weeks later. The analysis included four different unidimensional index scales of functional ability divided into two types, with reduced speed and tiredness as subdimensions. The two scale types were mobility function and lower limb function. Early losses of ability together with global self-rated health were treated as outcome measures of diagnosed chronic diseases. At the same time these outcome measures together with diagnosed diseases were considered to predict drug consumption and GP consultations. It was shown that functional ability as measured by the new index scales were strongly influenced by diagnosed diseases: arteriostenosis and osteoarthrosis in lower extremities, obesity, shoulder impairments and bronchitis among women, and glucose intolerance, arteriostenosis in lower extremities and shoulder impairments among men. Global self-rated health was strongly associated with the new functional ability rating system. Early losses of ability but not self-rated health was a strong predictor for drug consumption and frequent contacts with GP. It is concluded that the new measure of functional ability is suitable for health studies of community dwelling elderly, in particular as a summary statement of the individual's health status. PMID- 1432013 TI - Modelling result-specific likelihood ratios. PMID- 1432012 TI - Glucose tolerance and the risk of cardiovascular disease: the Zutphen Study. AB - The impact of glucose tolerance on the incidence of ischemic heart disease (IHD), cerebrovascular disease (CVA), and peripheral arterial disease (PAD) was investigated in the Zutphen Study. In 1970 a complete oral glucose tolerance test (GTT) was carried out on 400 normoglycemic men aged 50-70 yr. A morbidity follow up was completed in 1985. With GTT classified as the dichotomous variable using the median value of the area under the curve, elevated risks for IHD (RR = 1.6, p < 0.05), fatal IHD (RR = 2.3, p < 0.01), and CVA (RR = 1.9, p < 0.10) were observed, adjusted for potential confounders. No association with PAD was found. Also the risk among non-insulin-dependent diabetics (n = 46) was assessed. These men were clinically diagnosed between 1960 and 1985, median year of diagnosis being 1973, at age 61 yr. Compared with 230 matched non-diabetics increased risks were observed for fatal IHD (p = 0.05), CVA (p = 0.10) as well as PAD (p = 0.05). Thus an elevated risk for IHD, and possibly CVA, may have been found with lower levels of glucose than assumed previously, suggesting a continuous risk gradient. For PAD the relations with glucose tolerance are more complex. PMID- 1432014 TI - Rising mortality due to Parkinson's disease and amyotrophic lateral sclerosis: a manifestation of the competitive nature of human mortality. AB - Over the past 15 yr, a marked increase in crude mortality rates from Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) has occurred in the U.S. This is often attributed to as yet undefined environmental factors. The deterministic risk of general mortality and mortality due to PD, ALS, ischemic heart disease (IHD), and stroke for the years 1963, 1977, and 1986 in the U.S., as defined by the method of longitudinal Gompertzian analysis, were calculated and compared. When the rise in PD and ALS mortality is viewed from the perspective of deterministic and competitive mortality dynamics, it becomes evident that the major force increasing mortality from these two neurologic diseases is the declining mortality from IHD and stroke. Consequently, there is no need to invoke intrinsic etiologic alterations in the environment to account for the observed increases in PD and ALS mortality. Recognition of the competitive nature of human mortality illustrates the inherent risk of making etiopathogenic conclusions based upon single disease mortality data. PMID- 1432015 TI - Interobserver variability in medical record review: an epidemiological study of asthma. AB - Interobserver variability during the data collection for a large retrospective study of asthma was assessed. After extensive training by three physician investigators, two nurses collected study data from existing medical records using an explicit protocol. At four time intervals, samples of records already abstracted by one nurse were reviewed and re-abstracted by another nurse assigned to the project. The unweighted kappa coefficient was used to evaluate observer reliability. Most of the kappa coefficients were > or = 0.6, suggesting good to excellent agreement. Agreement was highest for demographic, clinical and medication variables, while judgement variables had the lowest kappa coefficients. The well known dependence of kappa on the prevalence of the variable studied was evident in these data. We strongly recommend periodic monitoring of observer reliability in any study using more than one individual to collect data to ensure reliable data collection. PMID- 1432016 TI - Risk of kidney cancer in analgesics users. AB - The risk of kidney cancer was examined in a cohort of people discharged from Danish hospitals from 1977-1987 with a diagnosis of rheumatoid arthritis, osteoarthrosis or backpain. These individuals are presumably more or less regular users of mild analgesics. A total of 155,554 people were identified. The risk of cancer of the urinary tract was slightly increased [relative risk (RR) = 1.31], almost exclusively because of an increased risk of renal cell carcinoma (RR = 1.40). The relative risk was higher in individuals with rheumatoid arthritis than among individuals with osteoarthrosis or backpain, and higher among women than men. Although this study lacks information on the actual analgesics consumption of the individual, and various biases may be present, these findings offer little support to the concern that increased analgesics use raises the risk of kidney cancer. PMID- 1432017 TI - Alcohol and epithelial ovarian cancer. AB - The relationship between alcohol consumption and the risk of epithelial ovarian cancer was analysed using data from a case-control study of 801 histologically confirmed epithelial ovarian cancers and 2114 controls in hospital for acute, non neoplastic, gynecological, or hormone-related conditions, admitted to a network of teaching and general hospitals in the greater Milan area, northern Italy, i.e. a region with comparatively frequent alcohol consumption by women. Compared to alcohol abstainers, the multivariate relative risks (RRs) were 1.0 [95% confidence interval (CI), 0.7 to 1.4] for less than one, 1.1. (95% CI 0.9 to 1.6) for one to two, 1.2 (95% CI 1.0 to 1.5) for two to three and 1.3 (95% CI 0.9 to 1.8) for three or more drinks per day. A significant direct trend in risk with dose emerged. This finding chiefly derived from an association between ovarian cancer risk and consumption of wine (which accounts for over 90% of alcohol intake in this female population). Although no significant interaction between the effect of alcohol consumption and various women's characteristics emerged, there was a hint that the adverse influence of alcohol consumption is more marked in middle-age and less educated women. Thus, the results of this study suggest that relatively elevated alcohol intake (of the order of 40 g per day or more) may cause a modest increase of epithelial ovarian cancer risk. PMID- 1432018 TI - Coffee drinking and the risk of adenomatous polyps. PMID- 1432019 TI - Smoking and coronary disease in women. PMID- 1432020 TI - Chance-corrected sensitivity and specificity for three-zone diagnostic tests. PMID- 1432021 TI - Trends in the utilization of non-steroidal anti-inflammatory drugs in the United States, 1986-1990. AB - National estimates of NSAID utilization were obtained from two databases available from IMS America. These data illustrate that in contrast to the rapid rise in NSAID prescriptions from 1973 (27.5 million) to 1983 (66.7 million), NSAID prescriptions have recently been remarkably stable. Over the same time period, a 46 fold increase in the use of gastro-protective and/or anti-ulcer drugs concomitantly with NSAID was demonstrated. It is hypothesized that the stabilization of NSAID prescription usage coupled with the dramatic increase in usage of concomitant anti-ulcer and gastro-protective agents has occurred due to physician awareness of the increased relative risk for adverse gastrointestinal events among NSAID users compared to non-users. PMID- 1432022 TI - The role of diagnostic inconsistency in changing rates of occurrence for coronary heart disease. AB - The ante-mortem (in vivo) and post-mortem diagnoses of coronary heart disease (CHD) were compared in necropsies at a university hospital for 1965, 1975, and 1985. The secular trends showed gradually rising proportions in both true positive and false negative ante-mortem diagnoses. Both types of change in diagnostic error would progressively lower the counted numbers of CHD in official vital statistics. With suitable statistical corrections, the occurrence rates of CHD in Connecticut became much higher and showed less dramatic trends in secular decline. The results indicate that major improvements in accuracy are needed before vital statistics data are accepted at face value and analyzed for biologic explanations of the changing numbers. PMID- 1432024 TI - Some observations on the variation in height coefficients in prediction equations for forced vital capacity. AB - Intercept and height coefficients in prediction equations for forced vital capacity (FVC) are highly correlated and highly variable, due in part to the small coefficient of variation of height (4%). This degree of imprecision and relationship was observed among the coefficients of a set of 26 unrelated published prediction equations, and appeared to dominate any systematic differences between them in methodology and technique. The findings indicate that care needs to be taken when using equations for predicting the FVC of people at the extremes of height. They also demonstrate the need for careful planning in the design of studies intended for the compilation of prediction equations, including provision for sufficient numbers of observations. Support is also given to the use of a composite formula based on the averaging of many individual prediction equations. The results are applicable to other similar and commonly used lung function equations (e.g. that for forced expiratory volume in 1 second, FEV1) that employ height as a predictor variable. PMID- 1432023 TI - Decision making during serious illness: what role do patients really want to play? AB - Two surveys were conducted to determine what roles people actually want to assume in selecting cancer treatments. 436 newly diagnosed cancer patients and 482 members of the general public participated. Preferences were elicited using two card sort procedures, each of which described five potential roles in decision making. Findings suggested that the impact of being diagnosed with a life threatening illness may influence preferences to participate. The majority (59%) of patients wanted physicians to make treatment decisions on their behalf, but 64% of the public thought they would want to select their own treatment if they developed cancer. Most patients (51%) and members of the public (46%) wanted their physician and family to share responsibility for decision making if they were too ill to participate. Sociodemographic variables accounted for only 15% of variance in preferences. These variables are not particularly useful in making predictions about which groups want more or less active roles in medical decision making. PMID- 1432025 TI - A prospective study of familial aggregation of blood pressure in young children. AB - In a prospective study, we evaluated familial aggregation of blood pressure in a sample of 175 normotensive families with children 3 to 6 yr old. Systolic and diastolic blood pressure measurements of parents and children were correlated at 1, 2, and 3 yr intervals. Spearman rank-order correlation coefficients between parents and children were significant for mother-son pairs. In particular, mother son blood pressure correlation coefficients were significant for systolic blood pressure across all 3 yr and for diastolic blood pressure during yr 2. Further analyses were performed adjusting for body mass index (BMI), age, physical activity, sodium intake, potassium intake, and parental smoking status, and alcohol use. The Spearman correlation coefficients for mother-son pairs remained significant for yr 1 and 3 after adjusting for these blood pressure correlates. These results are consistent with cross-sectional studies and suggest that both genetic and environmental contributions to blood pressure status are important in young children. PMID- 1432026 TI - Precision of blood cholesterol measurement and high blood cholesterol case finding and treatment. AB - Imprecise blood cholesterol measurement can be expected to adversely affect large scale efforts to detect and treat high blood cholesterol. Using protocols specified by the National Cholesterol Education Program (NCEP), we used computer simulation techniques to quantify the effects of blood cholesterol measurement variability on misclassification rates, costs, effectiveness, and cost effectiveness of high blood cholesterol case-finding and treatment. At the time of initial case-finding, increased measurement variability was associated with a moderate decrease in the proportions assigned to a treatment state and in the positive predictive value of such an assignment. After 10 years of continual case finding and treatment, measurement variability dramatically affected proportions assigned to drug treatment and diminished the percent on drugs with blood cholesterol levels truly above NCEP cutpoints. Extreme variability in blood cholesterol measurement increased per capita costs by 14-18% and diminished cost effectiveness by at least 11-12%. The adverse effects of measurement variability on cost-effectiveness were much more pronounced if adjustments to life-expectancy were made to recognize the lower quality of life associated with drug treatment. Misclassification rates can be decreased and cost-effectiveness improved by performing repeated measurements of blood cholesterol before increasing intensity of treatment. Improvement in the precision of measurement are especially beneficial for low-risk individuals. PMID- 1432027 TI - Within-subject diastolic blood pressure variability: implications for risk assessment and screening. AB - Because of variability in diastolic blood pressure within an individual, repeated measurements increase precision in assessing an individual's underlying mean pressure and so also aid risk classification. Data from a cohort of 11,299 middle aged men is used to model the variability in diastolic pressure between annual measurements. A simple model with pressure normally distributed about an underlying mean with standard deviation increasing with level fits the data very well. In modelling risk of cardiovascular mortality, a strong association is found with observed diastolic pressure level but not to trends in or variability between observed values. The effect of regression dilution is clear with the risk relationship appearing greater as one uses the mean of an increasing number of measurements. A method of adjusting for this regression dilution is described so giving an estimate of the relationship with underlying mean diastolic pressure. Using this survival model and the model for blood pressure variability, a method is presented for estimating both underlying mean pressure and absolute risk of cardiovascular disease given a sequence of blood pressure measurements from screening. This allows a sequential strategy for determining whether (a) antihypertensive intervention is desirable, (b) no further screening is necessary, or (c) further screening would aid the assessment, and emphasizes the need to consider blood pressure in the context of multiple risk factors. PMID- 1432028 TI - Twenty year trends in hospital discharges for asthma among members of a health maintenance organization. AB - We examined trends in hospitalizations for asthma from 1967 to 1987 among members of a large health maintenance organization. During this time asthma discharges increased significantly among children, and especially among boys under the age of 5 years. Ninety-five percent of the increase in discharges among boys was explained by a corresponding increase in the number of boys who were hospitalized. Increased readmissions did not account for the rise. Changes in the International Classification of Diseases coding of asthma and diagnostic shift by physicians accounted for only part of the increase. A decline in hospitalizations since 1984 may reflect changes in the management of asthma in the emergency room and not a decline in severe asthma episodes. PMID- 1432029 TI - The 56 kd platelet-derived growth factor (PDGF)-related protein is phosphorylated and the most stable form in human glioma cells. AB - We report herein the presence of a 56 kd platelet derived growth factor (PDGF) related protein as a phosphorylated form in human glioma cells. The phosphorylation of the 56 kd form was found to be the longest of all PDGF-related proteins. By Western blotting using a monoclonal anti-PDGF B-chain, the 80 kd, 56 kd, 40 kd, 28 kd and 17 kd PDGF-related proteins were detected, while after treatment among the nitrocellulose membrane transblotted cell extracts with alkaline phosphatase, 40 kd was the most densely observed while the 56 kd and 80 kd PDGF-related proteins were also detected. In a 32P flush labeling study, it was revealed that PDGF-related proteins incorporated with 32P were detected at 28, 32, 35, 40, 56 and 80 kd but the 17 kd monomer was not labeled. Among the labeled PDGF-related proteins, the 56 kd PDGF-related protein alone remained intracellularly for at least 16 hours. These results indicated that the PDGF related proteins in human glioma cells are synthesized in a phosphorylated form and partly remain in a 56 kd phosphorylated form intracellularly. The 56 kd form may thus be the most stable form and likely has a substantial biological effect. PMID- 1432030 TI - Effect of intracarotid infusion of etoposide with angiotensin II-induced hypertension on the blood-brain barrier and the brain tissue. AB - This study investigated the effects of the intracarotid infusion of etoposide in combination with angiotensin II (AT II)-induced hypertension on the blood-brain barrier (BBB) and brain tissue in rats. Eighty rats were divided into five groups: Group 1, intravenous infusion of AT II to increase arterial blood pressure; Group 2, intracarotid infusion of etoposide at 22.5 mg/m2 for 10 minutes; Group 3, intracarotid infusion of etoposide at 75.0 mg/m2 for 10 minutes; Group 4, intracarotid infusion of etoposide at 75.0 mg/m2 for 20 minutes; Group 5, intracarotid infusion of etoposide at 75.0 mg/m2 for 10 minutes with AT II-induced hypertension. Evans blue staining of the brain was used as a monitor of BBB disruption. Mean arterial blood pressure over the experimental period in Group 1 increased from 86.3 +/- 1.3 mmHg (mean +/- SEM) to 139.0 +/- 2.4 mmHg, and Group 5 from 85.9 +/- 1.8 mmHg to 137.3 +/- 2.4 mmHg. None of the animals in Group 1 and 2 showed any obvious neurological change, while all the animals in Group 3, 4 and 5 exhibited diminished activity as their sole neurological change throughout the course of the experiment. Slight evidence of BBB disruption was seen in only 25% of the animals in Group 1. Significant BBB disruption was found in the animals in Group 2, 3, 4 and 5. No histological change was observed in any animal in Group 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432031 TI - Temporal trends among childhood brain tumor biopsies. The Childhood Brain Tumor Consortium. AB - We sought temporal trends in the demographic, clinical, histologic feature, diagnostic class, and quality of life data over the interval 1930-1979 in the Childhood Brain Tumor Consortium database. The proportion of children younger than eight years old declined from 72% to 55% and the proportion of those older than ten more than doubled from 12% to 27%. The relative frequency of tumors in the supratentorial compartment increased significantly, while infratentorial tumors decreased. We found significant declines in supratentorial ependymomas and pilocytic astrocytomas. Similarly, some infratentorial tumors, especially ependymomas, decreased and brain stem tumors increased. Infratentorial medulloblastoma (primitive neuroectodermal tumor) increased significantly. Some individual histologic features which are markers of anaplasia increased in frequency in both supratentorial and infratentorial tumors. There was a significant increase in biopsies that contained nonneoplastic neural tissue in addition to tumor for both compartments and among supratentorial tumors there was a marked increase in the proportion of cases containing an indistinct neural tissue boundary. The probability of postoperative death declined, but the probability of survival five or ten years after surgery did not improve significantly for children who had tumors in either compartment. Among children who survived five years after the initial craniotomy, the proportion who had significant long term deficits increased. Most of this increase occurred in the last decade (1970-79). In this decade, the proportion of children for whom no deficits were reported five years following operation was 4% if they had a supratentorial tumor and 27% if they had an infratentorial tumor. The proportions of children alive five years following first surgery who had arachnoidal metastases increased significantly for infratentorial tumors. PMID- 1432033 TI - The role of radiotherapy in the treatment of subtotally resected benign meningiomas. AB - Thirty-six patients with benign meningioma were treated for primary or recurrent disease by subtotal resection and external beam irradiation from 1968-1986 at Massachusetts General Hospital. Comparison is made with 79 patients treated by subtotal surgery alone from 1962-1980. Progression-free survival for 17 patients irradiated after initial incomplete surgery was 88% at 8 years compared with 48% for similar patients treated by surgery alone (p = 0.057). 16 patients incompletely resected at time of first recurrence were irradiated and 78% were progression-free at 8 years while 11% of a similar group treated by surgery alone were progression free (p = 0.001). Long term overall survival was high and similar in both control and study groups. Two patients were irradiated at second recurrence and 1 patient at third recurrence. Twenty-five patients were treated with photons alone and have a median follow-up of 57 months, 6 patients have recurred at doses 45-60 Gy. Eleven patients were treated with combined 10 MV photons and 160 MV protons utilizing 3-D treatment planning. These patients have been followed for a median of 53 months and none have failed to date. Eight of 11 received 54-60.4 Gy and 3/11 greater than 64.48 Gy. Sex, age, pathology grade and score, surgery and timing of radiation therapy were not associated with significant differences in failure patterns within the irradiated study group (p less than 0.1). Complications have been seen in 6 irradiated patients. PMID- 1432034 TI - Low grade gliomas: comparison of intraoperative ultrasound characteristics with preoperative imaging studies. AB - Thirty-three patients with low grade gliomas were evaluated with preoperative computed tomography (CT), magnetic resonance (MR) and intraoperative ultrasound (IOUS). Six patients had undergone previous surgical exploration. Tumor borders were marked with cortical letters and corresponding depths calculated. Resection of tumor corresponded to these ultrasound dimensions. The histology of biopsy specimens from tumor and ultrasound determined margins was studied on formalin fixed permanent sections using hematoxylin and eosin (H&E) and immunocytochemistry (GFAP). Tumors were all seen on preoperative MR studies and most commonly showed a decreased T1 and increased T2 signal. Seven tumors showed variable enhancement with gadolinium. On CT two tumors were not seen, twenty three tumors were hypodense and eight hyperdense. Three tumors showed variable CT contrast enhancement. All tumors were hyperechoic on ultrasound. Twenty-five (75%) tumors were well defined with distinct margins compared to adjacent brain. Eight tumors had poorly defined borders on ultrasound; five (62%) of these lesions had previously undergone surgery. Eight tumors invaded functional brain identified by stimulation mapping techniques (e.g., speech cortex), thus limiting the resection. Five resections were limited because of involvement of important anatomical structures (e.g., corpus callosum). Of the remaining 20 tumors, seventeen (85%) had ultrasound defined margins that were histologically free of solid tumor (normal brain or sparse atypical cells only). Low grade gliomas are readily identified and their margins well defined by intraoperative ultrasound regardless of preoperative imaging patterns. The results suggest that IOUS may enhance intraoperative delineation and extent of resection for low grade gliomas. PMID- 1432035 TI - Growth of human acoustic neuromas, neurofibromas and schwannomas in the subrenal capsule and sciatic nerve of the nude mouse. AB - To develop a reproducible in vivo model for the growth of human acoustic neuromas and neurofibromas, we implanted tumor specimens (6 acoustic neuromas; 4 neurofibromas; 3 schwannomas arising in skin and soft tissues) from 13 different patients into the subrenal capsules of 67 nude mice and sciatic nerves of 64 nude mide. The animals were anesthetized and the tumors were microscopically implanted. Serial tumor volumes were determined at intervals up to 2 months by reopening the incision and directly measuring the tumor size with a micrometer. The percentages of acoustic neuromas that survived or grew were 57.1% in the subrenal capsule and 88.9% in the sciatic nerves; the percentages of neurofibromas that survived and grew were 50% in the subrenal capsule and 70% in the sciatic nerves; and the percentages of schwannomas that survived and grew were 57.1% in the subrenal capsule and 94.1% in the sciatic nerve. Tumors in the sciatic nerve also survived and grew for a longer period than those in the subrenal capsules. Tumor enlargement and stability correlated with neovascularity. At 1 or 2 months after engraftment, the tumors showed histologic appearances similar to the original tumors and immunohistochemical analysis of cryostat sections demonstrated staining of the tumors, but not the host mouse tissues for human beta 2-microglobulin, a species-specific marker. Furthermore, analysis of genomic DNA from implanted tumors revealed its human origin. We conclude that human acoustic neuromas, neurofibromas and schwannomas are readily grown in two sites in nude mice and that they retain their morphologic features and genomic identities. These tumors grow better and more consistently in the sciatic nerve than in the subrenal capsule. These are useful model systems for studying tumor growth and cellular modulation. PMID- 1432032 TI - Treatment of recurrent metastatic medulloblastoma with intensive chemotherapy and allogeneic bone marrow transplantation. AB - We report here the first known case of a patient with recurrent metastatic medulloblastoma to achieve long-term disease-free survival following treatment with allogeneic bone marrow transplantation. A 27 year old white male with recurrent metastatic medulloblastoma involving lymph nodes, bone and bone marrow was treated with multi-agent chemotherapy followed by allogeneic bone marrow transplantation from an HLA-identical sibling donor. Morbidity was acceptable with moderate to severe mucositis in the immediate post transplant period and clinical grade I graft versus host disease of the skin controlled with modest doses of corticosteroids. The patient continues in unmaintained complete remission in excess of 28 months with a performance status of 100%. Allogeneic marrow transplantation following cytoreductive salvage chemotherapy is an aggressive strategy that may offer an improved likelihood of disease eradication and ultimate cure for poor prognosis patients with recurrent metastatic medulloblastoma. PMID- 1432036 TI - Extraneural metastases in ependymoma. AB - Ependymomas, glial neoplasms usually arising in the posterior fossa or spinal cord, rarely metastasize outside the central nervous system. We have reviewed all 81 ependymomas evaluated at MSKCC between 1956-1989. Five (6.2%) had extraneural metastases (ENM). The primary tumor was in spinal cord in 3 patients and the cerebral hemisphere in 2. Two tumors were histologically anaplastic; 3 were histologically benign. The 5 patients were 3, 3, 3.5, 16 and 37 years old. Time from initial diagnosis to development of ENM was 0, 15, 35, 40, and 288 months. At the time of ENM the primary tumor was progressing in 4/5 patients. Prior therapy had included resection plus radiation therapy (RT) (1), RT plus chemotherapy (1), resection plus RT plus chemotherapy (2). One patient had not received prior therapy because ENM were present at diagnosis. The sites of ENM included lung and thoracic lymph nodes (2), pleura and peritoneum (2), and liver (1). Both patients with peritoneal ENM had had ventriculoperitoneal shunts. ENM did not correlate with histologic grade, age, or degree of surgical resection. When patients with ependymoma develop signs or symptoms of systemic disease such as abdominal pain, cough, or adenopathy, ENM should be considered. PMID- 1432037 TI - A case of treatment-related leukoencephalopathy: sequential MRI, CT and PET findings. AB - A case of treatment-related leukoencephalopathy is presented. A patient with medulloblastoma was postoperatively treated with craniospinal axis irradiation. One month after irradiation, weekly intrathecal administration of methotrexate was performed 4 times to treat cerebrospinal fluid dissemination of the tumor. Two months after the initiation of intrathecal chemotherapy, the patient became somnolent and developed decerebrate posturing. Magnetic resonance imaging showed diffuse leukoencephalopathy. Positron emission tomography revealed a diffuse decrease in glucose uptake in the deep white matter. Auditory evoked potential also showed diffuse abnormalities, not only in the cerebrum, but also in the brain stem. High dose intravenous leucovorin rescue was attempted without any neurologic improvement. PMID- 1432038 TI - Chemotherapy with vincristine (VCR) and etoposide (VP-16) in children with low grade astrocytoma. AB - Twenty patients, aged 6 months to 20 years, with low-grade astrocytoma (LGA) participated in a chemotherapy trial of vincristine (VCR) and etoposide (VP-16). Fourteen children had recurrent progressive disease at entry on study. Prior treatment consisted of surgical resection alone (6), surgical resection and irradiation (4), surgical resection, irradiation and chemotherapy (2), surgery and chemotherapy (1), and irradiation and chemotherapy (1). Six patients were treated at initial diagnosis of LGA because they were less than 5 years old (5) or for a second primary tumor (1). Four recurrent patients and 3 newly diagnosed patients underwent surgical debulking of their tumors immediately prior to study entry. Tumors were located in the optic nerve/chiasm/hypothalamus (8), brain stem/cerebellum (4), cerebral hemispheres (3), midline structures (3), and spinal cord (2). The treatment plan administered in an out-patient setting consisted of weekly VCR 1.5 mg/m2 for 7 to 8 weeks and VP-16 100 mg/m2 for 5 days repeated every 6 weeks for a total of 18 months of therapy. Responses were evaluated by computerized tomography or magnetic resonance imaging. Of the 20 patients, 1 exhibited a partial response maintained for 12+ months, 3 exhibited minor responses maintained for a period of 10+ to 35 months, and 11 maintained stable disease for 10 to 42 months. Of the 11 patients with stable disease, 2 were withdrawn early from the study without further therapy. Five of the 20 patients developed progressive disease; for 4 of these 5, this occurred during the first course of therapy. Subsequently, these 5 died due to tumor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432039 TI - Intrathecal ACNU treatment of B16 melanoma leptomeningeal metastasis in a new athymic rat model. AB - To evaluate new cytotoxic drugs for intrathecal treatment we developed an experimental model of leptomeningeal metastasis by intracisternal injection of 10(4) B16-F10 melanoma cells in nude rats. One hour in vitro incubation with 20 micrograms/ml ACNU (area under the drug concentration-time curve = 1200 microgramsxmin/ml) induced a 4-log kill of B16 melanoma cells. A single or repeated non-toxic dose of 1 mg/kg was injected into the cisterna magna of rats inoculated with tumor (area under the drug concentration-time curve assuming an even cerebrospinal fluid distribution greater than 7000 microgramsxmin/ml). Median survival free of symptoms was 16 days (range 14-27) for controls (n = 9) and 18 days (range 17-23) for rats treated with ACNU on day 4 (n = 9). Animals treated both on day 2 and 8 (n = 8) developed symptoms on day 21 (range 13-35). Neurological symptoms and neuropathological examination in animals with increased survival indicated local suppression of tumor growth in the cisterna magna but increased spinal seeding and mass growth. From these results and the available pharmacokinetic data on ACNU it is concluded that bolus injection of ACNU- although locally effective--is not a sufficient treatment of widespread leptomeningeal metastasis. An increased therapeutic efficacy might be achieved by ventriculolumbar perfusion. PMID- 1432040 TI - A motor area rostral to the supplementary motor area (presupplementary motor area) in the monkey: neuronal activity during a learned motor task. AB - 1. The rostromesial agranular frontal cortex of macaque monkey (Macaca fuscata), traditionally defined as the supplementary motor area (SMA), was studied using various physiological techniques to delineate two different areas rostrocaudally. 2. Field and unitary responses to electrical stimulation of the primary motor cortex were distinct in the caudal part, but minimal or absent in the rostral part. Intracortical microstimulation readily evoked limb or orofacial movements in the caudal part, but only infrequently in the rostral part. Neuronal responses to visual stimuli prevailed in the rostral part, but somatosensory responses were rare. The opposite was true in the caudal part. 3. The rostral part, roughly corresponding to area 6a beta, was operationally defined as the presupplementary motor area (pre-SMA). The caudal part was redefined as the SMA proper. 4. Single cell activity in the pre-SMA was quantitatively compared with that in the SMA proper in relation to a trained motor task. 5. Phasic responses to visual cue signals indicating the direction of forthcoming arm-reaching movement were more abundant in the pre-SMA. 6. Activity changes during the preparatory period, which lasted until the occurrence of the trigger signal for the reaching movement, were more frequent in the pre-SMA. 7. Phasic, movement-related activity was more frequent in the SMA, and its onset was often time locked to the movement onset. In the pre-SMA, the occurrences of response time locked to the movement-trigger signal were more frequent than in the SMA. 8. Among neurons in both areas, directional selectivity was found in all the cue, preparatory, and movement related responses. PMID- 1432041 TI - Action of brain stem reticular afferents on lagged and nonlagged cells in the cat lateral geniculate nucleus. AB - 1. The A-laminae of the cat lateral geniculate nucleus (LGN) contain two distinct groups of relay neurons: lagged and nonlagged cells. The groups differ in the pattern, timing, and amplitude of response to flashing spots. At spot onset, nonlagged cells discharge at short latency with an excitatory transient; in lagged cells this transient is supplanted by an inhibitory dip and a delayed latency to discharge. At spot offset, lagged cell discharge decays more slowly than in nonlagged cells. Here we have investigated the facilitatory influence of the brain stem reticular formation on the response properties of lagged X-cells (XL) and nonlagged X- and Y-cells (XN and YN). We were particularly interested in whether the inhibitory dip and sluggish response of lagged cells could be reversed during brain stem activation and the cells induced to respond like nonlagged cells. The peribrachial region (PB) of the pontine reticular formation was stimulated electrically with the use of 1,100-ms-long pulse trains that were paired with flashing spot stimuli. 2. Stimulation of PB led to an increase in the amplitude of visually evoked discharge in lagged and nonlagged cells. Compared with their response to spot stimulation alone, the average PB-evoked increase in mean discharge rate was greater than 50% in both groups. The mean discharge rate during PB plus spot stimulation was somewhat higher for XN-cells than for YN- and XL-cells, reflecting the relatively higher discharge rate among XN-cells during spot stimulation alone. 3. Two measures of response timing characterize lagged and nonlagged cells: latency to half-maximal discharge at spot onset (half rise) and latency to half-minimal discharge at spot offset (half fall). Among XN- and YN-cells, PB stimulation had no significant effect on these two latencies; among XL-cells, both latencies were reduced by 43 and 35%, respectively, on average. 4. During spot stimulation alone, all lagged cells were distinguishable from all nonlagged cells in having half-rise and half-fall latencies greater than 60 ms. Despite the reduction among XL-cells in these 2 latencies during PB stimulation, all but 2 of the 40 XL-cells maintained laggedlike latencies. The majority (95%) of XL-cells remained unambiguously lagged on these measures during brain stem stimulation. 5. During spot stimulation alone, 30 of 40 XL-cells tested displayed a prominent and often long-lasting inhibitory dip in discharge starting approximately 45 ms after spot onset. During PB stimulation only three cells lost the dip.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432042 TI - GABAergic inhibition of neuronal activity in the primate motor and premotor cortex during voluntary movement. AB - 1. The functional role of GABAergic inhibition in neuronal activity in the forearm-hand area of the motor cortex and the postarcuate premotor cortex was studied while monkeys pressed and released a lever in response to a visual cue. gamma-Aminobutyric acid (GABA), its agonist muscimol (MUS), and its antagonist bicuculline methiodide (BMI), as well as acetylcholine, noradrenaline, and sodium glutamate, were applied iontophoretically to isolated single neurons whose activity was recorded via glass micropipettes that contained carbon fibers. 2. The activity from single neurons recorded in the motor and premotor cortex showed changes during the press or release of the lever by movement of the contralateral wrist. Discharge of most of the movement-related neurons (greater than 90%) was decreased or completely suppressed by iontophoretically applied GABA or MUS. 3. The activity of the movement-related neurons increased after application of BMI. In 70% of neurons tested, the activity during application of BMI was specifically enhanced at or near the phase of their peaks of activity, with or without a noticeable elevation in background activity. 4. About 10% of the neurons that had been unidirectional (i.e., neurons that showed a change in activity at either the lever-press or lever-release phase) became bidirectional (i.e., they showed changes in activity at both phases) when GABA transmission was blocked by the application of BMI. Bidirectional neurons also showed a reduction in the value of the directionality index. 5. One-half of the silent neurons, which had not shown any activity during either the lever-release or the lever-press phase, became active during the movement phases that followed application of BMI. 6. Most of the cortical neurons in layers II-VI in the motor area were found to be subject to GABAergic inhibition during voluntary movement. 7. We conclude that GABAergic inhibition plays a role in regulating the population of task-related neurons, and the levels of the task-related activity. GABAergic inhibition also improves directionality index in the motor cortex neurons to control the activity of target muscles. PMID- 1432043 TI - Parallel processing in rabbit first (SI) and second (SII) somatosensory cortical areas: effects of reversible inactivation by cooling of SI on responses in SII. AB - 1. Previous observations on the effect of ablation or inactivation of the primary somatosensory cortex (SI) on the responses of neurons within the second somatosensory area (SII) to tactile stimuli point to profound differences between monkeys and certain other mammals in the organization of thalamocortical systems. In the cat, for example, tactile information appears to be conveyed in parallel from the thalamus to both SI and SII, whereas, in macaque and marmoset monkeys, it is conveyed in a serial (or hierarchical) scheme from the thalamus to SI and thence to SII. The present study examined the responses of individual SII neurons during reversible, cooling-induced inactivation of SI in another nonprimate placental mammal, the rabbit, to obtain further evidence on whether the above differences might reflect a fundamental distinction between simian primates and other mammalian species. 2. When the temperature at the face of a silver cooling block over the forepaw and hindpaw regions of SI was lowered to 5-13 degrees C, the SI surface potentials evoked by brief tactile stimuli were abolished (indicative of SI inactivation), whereas SII potentials remained intact. 3. The responses of 25 SII neurons to controlled tactile stimuli (consisting of 1- to 1.5-s trains of vibration or rectangular mechanical pulses) were studied before, during, and after inactivation of SI. The effects on the spontaneous activity of a further three SII neurons that lacked identified receptive fields were also studied. 4. The response or activity levels of 26 of the 28 SII neurons examined (93%) were unaffected by SI inactivation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432044 TI - Relationship between receptive and dendritic field size of amacrine cells in the rabbit retina. AB - 1. Intracellular recordings were obtained from 40 amacrine cells in the isolated, superfused retina eyecup of the rabbit. Cells were subsequently labeled with horseradish peroxidase for morphological identification. Many of these cells displayed dendritic morphology consistent with that of amacrine cells described in prior anatomic studies, including starburst, A17, AII, and DAPI-3 cells. 2. The center receptive field of amacrine cells was measured with a 50- or 95 microns-wide, 6.0-mm-long rectangular slit of light that was displaced along its minor axis (parallel to the visual streak) in increments as small as 3 microns. The extent of the receptive field was calculated as the total distance over which the displaced slit could evoke a center response. Area summation of amacrine cells was measured with concentric spots of light with increasing diameters centered over the cell. 3. For a single amacrine cell, the receptive field size was comparable to the extent of its dendritic arbor. For the total population of amacrine cells, there was a strong, linear relationship between receptive field and dendritic field size. The receptive fields were, on average, 27% larger than the corresponding dendritic arbors, but this discrepancy can be accounted for entirely by tissue shrinkage associated with histological processing and a small imprecision of the light stimuli. Area summation measurements were consistent with those of receptive fields and were also related linearly to the dendritic field size of cells. 4. These findings indicate that even when the slit of light was placed at the distal edges of the dendritic arbor, synaptic inputs activated there were propagated effectively to the soma and recorded by microelectrodes placed there. In addition, amacrine cells were capable of summating synaptic inputs distributed throughout the entire arbor. 5. These results are inconsistent with the findings of prior computational modeling studies of passive, dendritic current flow in A17 and starburst amacrine cells that synaptic inputs on distal dendritic branches are isolated electrically from the soma and that these branches form autonomous, functional subunits. 6. The majority of amacrine cells encountered displayed light-evoked and/or spontaneous action potentials. These action potentials often took the form of high-amplitude somatic and low-amplitude dendritic spikes. On average, spiking amacrine cells showed considerably larger dendritic fields than nonspiking amacrine cells. In fact, all amacrine cells with arbors greater than 436 microns, which formed 45% of the total population, displayed spike activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432045 TI - Some properties of receptive fields of olfactory mitral/tufted cells in the frog. AB - 1. Different regions of the frog's olfactory epithelium were stimulated with nine glass micropipettes either individually or simultaneously in different combinations. The stimulus was a positive electrical pulse (4 s) consisting of a progressive increase, a plateau, and a progressive decrease in current intensity. Extra- and intracellular recordings were made from olfactory bulb mitral/tufted cells. Some of these cells were identified by intracellular injection of Lucifer yellow. 2. The action potential response patterns of mitral/tufted cells during the different phases of the stimulation were coded according to whether the activity was increased or decreased compared with its spontaneous level just before stimulation. Neural responses were classified into 11 types: individual neurons responded with different response types to stimuli delivered at different epithelial sites. On the basis of these response types, it was found that neurons could be classified into two groups. All response types in one group included an initial phase of increased discharge (excitation), whereas all types in the other group included an initial phase of decreased activity (suppression). Neurons that displayed response types belonging to one group never displayed those of the other group. It was thus concluded that a given neuron responded either always with an increased activity or always with a decreased activity, whatever the location of the stimulus. 3. The receptive field of a mitral/tufted cell appeared to be homogenous and not divided into areas of different properties, at least under the present experimental conditions. The extent of a receptive field was estimated by determining the number of effective epithelial sites (where an electrical stimulus evoked a response from a bulbar neuron).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432046 TI - Expression of the mRNAs for the Kv3.1 potassium channel gene in the adult and developing rat brain. AB - 1. The gene for a mammalian Shaw K+ channel has recently been cloned and has been shown, by alternative splicing, to give rise to two different transcripts, Kv3.1 alpha and Kv3.1 beta. To determine whether these channels are associated with specific types of neurons and to determine whether or not the alternately spliced K+ channel variants are differentially expressed, we used ribonuclease (RNase) protection assays and in situ hybridization histochemistry to localize the specific subsets of neurons containing Kv3.1 alpha and Kv3.1 beta mRNAs in the adult and developing rat brain. 2. In situ hybridization histochemistry revealed a heterogeneous expression pattern of Kv3.1 alpha mRNA in the adult rat brain. Highest Kv3.1 alpha mRNA levels were expressed in the cerebellum. High levels of hybridization were also detected in the globus pallidus, subthalamus, and substantia nigra reticulata. Many thalamic nuclei, but in particular the reticular thalamic nucleus, hybridized well to Kv3.1 alpha-specific probes. A subpopulation of cells in the cortex and hippocampus, which by their distribution and number may represent interneurons, were also found to contain high levels of Kv3.1 alpha mRNA. In the brain stem, many nuclei, including the inferior colliculus and the cochlear and vestibular nuclei, also express Kv3.1 alpha mRNA. Low or undetectable levels of Kv3.1 alpha mRNA were found in the caudate-putamen, olfactory tubercle, amygdala, and hypothalamus. 3. Kv3.1 beta mRNA was also detected in the adult rat brain by both RNase protection assays and by in situ hybridization experiments. Although the beta splice variant is expressed at lower levels than the alpha species, the overall expression pattern for both mRNAs is similar, indicating that both splice variants co-expressed in the same neurons. 4. The expression of Kv3.1 alpha and Kv3.1 beta transcripts was examined throughout development. Kv3.1 alpha mRNA is detected as early as embryonic day 17 and then increases gradually until approximately postnatal day 10, when there is a large increase in the amount of Kv3.1 alpha mRNA. Interestingly, the expression of Kv3.1 beta mRNA only increases gradually during the developmental time frame examined. Densitometric measurements indicated that Kv3.1 alpha is the predominant splice variant found in neurons of the adult brain, whereas Kv3.1 beta appears to be the predominant species in embryonic and perinatal neurons. 5. Most of the neurons that express the Kv3.1 transcripts have been characterized electrophysiologically to have narrow action potentials and display high frequency firing rates with little or no spike adaptation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432047 TI - ATP-gated current in dissociated rat nucleus solitarii neurons. AB - 1. The excitatory response of extracellularly applied ATP was investigated in freshly dissociated rat nucleus tractus solitarii neurons under whole-cell configuration using the "concentration-clamp" technique. 2. At a holding potential of -70 mV, 100 microM ATP evoked inward current that was slowly desensitized in the continuous presence of ATP. The ATP-gated current increased in a concentration-dependent manner over the concentration range between 10 microM and 1 mM. The half-maximum concentration was 31 microM and the Hill coefficient was 1.2. 3. The potency of ATP analogues for the purinergic receptor was in the order of ATP = 2-methylthio-ATP much greater than ADP greater than alpha,beta-methylene ATP. Neither adenosine nor AMP evoked any responses. The order was consistent with a P2y receptor subtype. 4. The current-voltage relationship for the 100 microM ATP response showed a clear inward rectification at positive potentials beyond -50 mV. The reversal potential of the ATP-gated current was +13 mV. 5. The time constants of activation and inactivation of the ATP-gated current solution were dependent on the extracellular ATP concentration, and both kinetics became faster at higher ATP concentrations. 6. The ATP-gated current was also elicited in an external solution containing Ca2+ as a permeable cation. The inactivation kinetics in an external solution containing 75 mM Ca2+ were faster than those in an external solution with 150 mM Na+. 7. Calculated relative permeability ratios were PNa/PCs = 1.64 ([Na+]o = 30-150 mM), PCa/PCs = 2.17 ([Ca2+]o = 2 mM). Anions were not measurably permeable in this preparation. PMID- 1432048 TI - Dendritic origin of late events in optical recordings from salamander olfactory bulb. AB - 1. Optical recordings of membrane-potential changes were used to characterize the origin and properties of the electrical signals from the dendritic level in slices of the salamander olfactory bulb. 2. The optical events were correlated with field-potential waves recorded simultaneously. Both responses exhibited patterns similar to those found in other species. 3. Orthodromic stimulation evoked a compound action potential in the olfactory nerve fibers, followed by two additional principal waves (N1 and N2). These field-potential waves reflected excitatory postsynaptic potentials at the primary mitral/tufted and granule cell dendrites, respectively. 4. Extrinsic optical signals from horizontal slices stained with the pyrazo-oxonal dye RH-155 showed a characteristic sequence of depolarizing and hyperpolarizing events. All of the signals exhibited a wavelength dependence expected for this dye and were abolished in the presence of high K+ in the bath. 5. According to their time courses, depolarizing responses under normal recording conditions were divided into two components, fast and slow. Orthodromic stimuli evoked a fast presynaptic response that represents synchronous compound action potentials from olfactory nerve fibers. At subglomerular levels, additional fast responses could often be recorded at the peri/subglomerular level and in the mitral/tufted somata region. These postsynaptic responses partially coincided with the rising phase of a different depolarizing signal, a slow component characterized by its prolonged time course. 6. With orthodromic stimulation, this slow signal attained its largest amplitude in the zone between the glomeruli and the superficial part of the external plexiform layer (EPL). Antidromic stimuli evoked a signal with some similarities to the one evoked orthodromically, but originating in deeper EPL regions. 7. Slow components were characterized by their Ca dependence. Low Ca2+ medium, or calcium channel blockers, suppressed this optical component, whether evoked orthodromically, antidromically, or by direct stimulation. In addition, Ba2+ (2.5 3.6 mM) in the bath did not abolish these responses, suggesting that they do not reflect a glial depolarization in response to elevated extracellular K+ concentration ([K+]o). 8. Locally applied stimuli next to the glomerular layer elicited these signals in 5-10 microM tetrodotoxin (TTX) or in low extracellular Na+ concentration ([Na+]o) medium, but antidromic or orthodromic stimuli failed to evoke the response under these conditions. The sizes of the responses to local stimuli remained constant, but an increase in their duration was observed in either TTX or low [Na+]o. 9. gamma-Aminobutyric acid (GABA) and baclofen reduced the size of the slow components in a dose-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432049 TI - Acoustic reflex frequency selectivity in single stapedius motoneurons of the cat. AB - 1. The sound frequency selectivities of single stapedius motoneurons were investigated in ketamine anesthetized and in decerebrate cats by recording from axons in the small nerve fascicles entering the stapedius muscle. 2. Stapedius motoneuron tuning curves (TCs) were very broad, similar to the tuning of the overall acoustic reflexes as determined by electromyographic recordings. The lowest thresholds were usually for sound frequencies between 1 and 2 kHz, although many TCs also had a second sensitive region in the 6- to 12-kHz range. The broad tuning of stapedius motoneurons implies that inputs derived from different cochlear frequency regions (which are narrowly tuned) must converge at a point central to the stapedius motoneuron outputs, possibly at the motoneuron somata. 3. There were only small differences in tuning among the four previously described groups of stapedius motoneurons categorized by sensitivity to ipsilateral and contralateral sound. The gradation in high-frequency versus low frequency sensitivity across motoneurons suggests there are not distinct subgroups of stapedius motoneurons, based on their TCs. 4. The thresholds and shapes of stapedius motoneuron TCs support the hypothesis that the stapedius acoustic reflex is triggered by summed activity of low-spontaneous-rate auditory nerve fibers with both low and high characteristic frequencies (CFs). Excitation of high-CF auditory nerve fibers by sound in their TC "tails" is probably an important factor in eliciting the reflex. 5. In general, the most sensitive frequency for stapedius motoneurons is higher than the frequency at which stapedius contractions produce the greatest attenuation of middle ear transmission. We argue that this is true because the main function of the stapedius acoustic reflex is to reduce the masking of responses to high-frequency sounds produced by low-frequency sounds. PMID- 1432050 TI - Responses of neurons in the gracile nucleus of cats to innocuous and noxious stimuli: basic characterization and antidromic activation from the thalamus. AB - 1. Responses to innocuous and noxious mechanical and thermal stimuli were recorded from 90 neurons in the gracile nucleus of anesthetized cats. Cells were tested by antidromic activation for projections to the contralateral ventrobasal thalamus. 2. Cells were characterized broadly by their responses to mechanical stimuli as 1) responding only to tapping (16%), 2) fast-adapting to low-intensity mechanical stimuli (33%), or 3) slowly adapting (51%; most with a fast-adapting component to their responses). All fast-adapting cells and those slowly adapting cells that were tested with noxious heat were further categorized on the basis of their patterns of firing and responses to stimuli. These plus the tap-responsive cells comprised a more restricted sample of 76 categorized cells. 3. Many (22) slowly adapting cells responded to noxious heat (69% of tested slowly adapting cells; 29% of all categorized cells), either on the first application (9 cells) or after sensitization (13 cells), indicating input originating in nociceptors. Nearly all of these (21) responded more to intense pressure than to innocuous pressure. The majority of slowly adapting cells not responsive to noxious heat (5 of 8) or not tested with it (8 of 12) also responded more to intense than to innocuous pressure, suggesting possible input originating in nociceptors. Most cells that responded to noxious heat also had both rapidly and slowly adapting responses with low thresholds. Many were recorded in the range of the cluster region of the gracile nucleus. 4. Cells antidromically activated from the thalamus projected to the rostral part of the ventral posterior lateral nucleus, regardless of their physiological category, and included many with nociceptive input. Latencies of antidromic activation were shorter at more caudal locations in the gracile nucleus, indicating higher conduction velocities to the thalamus. Responses of antidromically activated cells to low-intensity phasic stimuli tended to be greater than those of cells not antidromically activated. 5. Background activity of the neurons was low, most firing at less than one spike/s. Antidromically activated cells had higher background activity than cells not antidromically activated. 6. The results indicate a greater proportion and more widespread distribution of cells with nociceptive input in the cat gracile nucleus than has been previously recognized. Many of these projected to the ventrobasal thalamus, showing that information originating in nociceptors can reach the thalamus through a dorsal column-medial lemniscal pathway in cats. PMID- 1432051 TI - Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons. AB - 1. The effects of metabotropic glutamate receptor (mGluR) stimulation on whole cell Ca2+ currents were studied in pyramidal neurons isolated from the dorsal frontoparietal neocortex of rat. The selective mGluR agonist cis-(+/-)-1 aminocyclopentane-1,3-dicarboxylic acid [trans-ACPD (100 microM)] suppressed the peak high-threshold Ca2+ current by 21 +/- 1.7% (mean +/- SE) in 40 of 43 cells from 10- to 21-day-old rats. Consistent with previous findings for mGluR, glutamate, quisqualate, and ibotenate [but not alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA)] reduced the Ca2+ currents, and the responses were not blocked by the ionotropic glutamate receptor antagonists 6-cyano-7-nitro quinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). EC50S for Ca2+ current suppression were 29 nM for quisqualate, 2.3 microM for glutamate, and 13 microM for trans-ACPD. 2. The low-threshold Ca2+ current was not modulated by trans-ACPD. The component of the high-threshold CA2+ current suppressed by mGluR was determined by pharmacology; the responses were not affected by omega-conotoxin GVIA but were occluded by the dihydropyridine Ca2+ antagonist nifedipine. Ca2+ tail currents prolonged by the dihydropyridine Ca2+ agonist (+)-SDZ 202-79] were suppressed by mGluR stimulation in parallel with the peak current. These findings strongly suggest that L-type Ca2+ channels are modulated by mGluR. 3. In neurons dialyzed with 100 microM guanosine 5'-(gamma thio)triphosphate (GTP-gamma-S), Ca2+ current suppression was elicited by the first application of trans-ACPD (in 5 of 6 cells), but not by subsequent applications. Responses in neurons dialyzed with 2 mM guanosine 5'-(beta thio)diphosphate (GDP-beta-S) were significantly smaller than controls. The results are consistent with mGluR acting via linkage to a G protein. 4. The responses to mGluR agonists were smaller when the external Ca2+ was replaced by Ba2+, indicating that some part of the mechanism underlying the current suppression is Ca2+ dependent. Because mGluR stimulates phosphoinositide turnover and release of Ca2+ from intracellular stores in other types of neurons, the possibility of released Ca2+ mediating inactivation of Ca2+ channels was considered. However, the Ca2+ current suppression was not attenuated by strong intracellular Ca2+ buffering [20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)], by dialysis with 100 microM inositol-1,4,5-triphosphate (IP3), or by external application of 1 microM thapsigargin. 5. We conclude that in neocortical neurons, one action of mGluR is to suppress the component of high threshold Ca2+ current conducted by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432052 TI - Sensory processing and corollary discharge effects in the mormyromast regions of the mormyrid electrosensory lobe. I. Field potentials, cellular activity in associated structures. AB - 1. This is the first of a series of papers on the electrosensory lobe and closely associated structures in electric fish of the family Mormyridae. The study describes the neuronal responses to sensory stimuli and to corollary discharge signals associated with the motor command that drives the electric organ discharge (EOD). The study is focused on the regions of the electrosensory lobe where primary afferent fibers from mormyromast electroreceptors terminate. 2. This first paper of the series describes the field potentials in the caudal lobe of the cerebellum and in the electrosensory lobe. It also describes the different types of unit activity in the caudal lobe of the cerebellum. Granule cells of the caudal lobe of the cerebellum provide the parallel fibers for most of the molecular layer of the electrosensory lobe. Determination of the input and responses of these cells is therefore an important part of the effort to understand the electrosensory lobe. 3. Corollary discharge field potentials evoked by the EOD motor command are very prominent in the caudal lobe of the cerebellum and in the electrosensory lobe. The potentials indicate that corollary discharge excitation affects first the granule cells of the caudal lobe and then, a few milliseconds later, the deeper cellular layers of the electrosensory lobe. The prominence and complexity of the field potentials indicate that corollary discharge signals have an important and varied role in the processing of electrosensory information by the mormyrid electrosensory lobe. 4. The field potentials evoked by electrosensory stimuli suggest that direct primary afferent excitation is limited to the granule and intermediate layers of the electrosensory lobe, as is indicated also by anatomic studies. 5. Proprioceptive units are the most common type of unit recorded in the granule cell region of the caudal lobe of the cerebellum (eminentia granularis posterior). These units have a regular discharge rate that changes tonically in response to slight bending of the trunk, bending of the tail, or bending of individual fins. Proprioceptive input will have a strong effect on the molecular layer of the electrosensory lobe and will thus modulate the responses of electrosensory lobe cells to electrosensory stimuli. Such proprioceptive input to the electrosensory lobe would allow the expected effects of body position changes to be accounted for in the processing of electrosensory information. 6. Units with stereotyped, short latency corollary discharge bursts to the EOD motor command were the next most common type of unit in the eminentia granularis posterior. These corollary discharge units were not affected by sensory stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432053 TI - Sensory processing and corollary discharge effects in mormyromast regions of mormyrid electrosensory lobe. II. Cell types and corollary discharge plasticity. AB - 1. This is the second of a series of papers on the electrosensory lobe and closely associated structures in electric fish of the family Mormyridae. The focus of the study is on the regions of the electrosensory lobe where primary afferent fibers from mormyromast electroreceptors terminate. 2. This second paper examines the responses of single cells in the mormyromast regions of the electrosensory lobe to electrosensory stimuli and to corollary discharge signals associated with the motor command that drives the electric organ to discharge. All recordings were extracellular. 3. Two major types of cells were identified: I cells, which were inhibited by electrosensory stimuli in the center of their receptive fields; and E cells, which were excited by such stimuli. 4. I cells and E cells shared a number of common features. Both types could have small receptive fields limited to only a few electroreceptors (3-5), and both types were markedly affected by the corollary discharge of the electric organ discharge (EOD) motor command. Cells of both types also showed clear plasticity in their responses to the corollary discharge or to the corollary discharge plus a stimulus. 5. I cells could be subdivided into three subtypes, I1, I2, and I3, on the basis of corollary discharge responses in the absence of sensory stimuli. I1 and I2 cells showed consistent corollary discharge bursts with little or no additional activity beyond the duration of the burst. The corollary discharge bursts of I1 cells were more stereotyped and of shorter latency than those of I2 cells. I3 cells had more spontaneous activity than I1 or I2 cells and minimal cells had more spontaneous activity than I1 or I2 cells and minimal corollary discharge responses in the absence of sensory stimuli. Field potentials indicated that all three subtypes of I cells were recorded in or near the ganglion layer of the electrosensory lobe. 6. Corollary discharge responses were plastic and depended on recent pairing of a sensory stimulus with the EOD motor command. Such plasticity was clearer in I2 and I3 cells than in I1 cells. Inhibitory sensory stimuli were paired with the EOD motor command for periods of a few seconds to several minutes. Such pairing resulted in a marked enhancement of the corollary discharge response in I2 cells, as shown by examining the effect of the motor command after turning off the stimulus. In I3 cells, such pairing resulted in a clear corollary burst to the command at the time of the previously paired inhibition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432054 TI - Influence of velocity and direction of surface-parallel cutaneous stimuli on responses of mechanoreceptors in feline hairy skin. AB - 1. The responses of cutaneous mechanoreceptors in feline hairy skin were examined in vivo with systematic variations in the velocity and direction of stimulus motion across the receptive fields (RF). The mechanoreceptor classes studied were guard hair afferents, field afferents, down hair afferents, and slowly adapting type I (SAI) mechanoreceptors. A camel's hair brush, moved by a high-precision motor, provided surface-parallel stimulation at velocities ranging from 0.4 to 100 cm/s. The stimulating device and protocols were similar to those previously used to evaluate human perception, thus allowing direct comparison of the two sets of data. 2. Each mechanoreceptor produced highly reliable mean firing rates with repeated stimulation. All mechanoreceptors showed a growth in evoked activity with increased stimulus velocity. With few exceptions, the relationship between brush velocity and mean firing rate was well described by a power function throughout the range of velocities tested. The exponents of these power functions, reflecting the degree of velocity dependency for each mechanoreceptor, were largest for the field type 1 units (F1) and guard hair type 1 units (G1). 3. The capacity of the mechanoreceptors to discriminate velocity was examined in the context of signal detection theory. For each unit, a velocity discriminability estimate (velocity delta'e) was calculated for responses to 5 versus 10 cm/s brushing and 10 versus 20 cm/s. The G1 and F1 units exhibited the largest velocity delta'e values, which were comparable to human velocity discriminability (d'e) values. Thus these data show the quantitative parallel between the velocity discriminability of G1 and F1 mechanoreceptors and of human perception similarly tested. 4. Most mechanoreceptors generated different response rates with stimuli moving in opposing directions (in the proximal-distal axis of the hindlimb). However, no mechanoreceptor class showed a consistently preferred direction of movement. A directional delta'e value was calculated for each mechanoreceptor at each stimulus velocity. These values were quite variable, even within a single mechanoreceptor class. In general, a mechanoreceptor's directional delta'e value either 1) decreased with increasing velocity or 2) remained constant across velocities. The way in which human directional discriminability varies with stimulus velocity did not parallel the way in which mechanoreceptor's directional delta'e values varied with the same range of stimulus velocities. 5. Some mechanoreceptors were tested with both the standardized brush, which was smaller than most mechanoreceptors' RFs, and a much larger brush, which was at least twice the size of the mechanoreceptors' RFs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432055 TI - Mechanisms of gastric rhythm generation in the isolated stomatogastric ganglion of spiny lobsters: bursting pacemaker potentials, synaptic interactions, and muscarinic modulation. AB - 1. The gastric central pattern generator (CPG), located in the stomatogastric ganglion (STG) of the spiny lobster (Panulirus interruptus), is nonrhythmic when deprived of neuromodulatory inputs from anterior ganglia. Leaving these inputs intact in vitro can sustain a gastric rhythm but also introduces numerous, uncontrolled and largely unknown modulatory and synaptic influences that greatly complicate analysis of this CPG. 2. Here we induced gastric rhythms in the isolated STG, by superfusing a specific modulator, the muscarinic agonist, pilocarpine. Muscarinic agents sustain vigorous gastric rhythms in the isolated STG. Our aim was to analyze the pattern-generating functions of the restricted gastric circuit, free of complicating influences from other ganglia, and under specific (muscarinic) modulation. 3. We used combinations of multiple cell hyperpolarizations, photodeletions, and synaptic blockade by picrotoxin to assess the pattern-generating role of individual gastric neurons and to study the activity of subcircuits. 4. Four identified gastric neurons [lateral gastric (LG), dorsal gastric (DG), 2 electrically coupled lateral posterior gastric (2LPGs)] acted as pattern-generating cells. They showed bursting pacemaker potentials (BPPs), i.e., plateau (or driver) potentials that underlay bursts of axonal spikes and slow, interburst depolarizing potentials that underlay repetitive burst activity. LG and DG, at least, became conditional bursters, able to burst repetitively because of intrinsic oscillations. The other gastric neurons behaved mainly as follower cells and derived their rhythmic bursting from synaptic coupling to the pattern-generator cells and from their own intrinsic (but nonoscillatory) properties. 5. The pattern-generating neurons form a novel "kernel" circuit that works by the cooperative interaction of cellular properties and synaptic connectivity. 6. This study constitutes the first complete and fully consistent analysis of pattern generation in the gastric network of the isolated STG. These mechanisms pertain to muscarinic rhythms in particular but also, we suggest, to gastric rhythm generation and CPG function in general. We suggest that 1) rhythmicity normally depends on the induction of bursty membrane properties in at least some component neurons; 2) different subcircuits can produce rhythmic patterns and may be activated by different modulators; and 3) the gastric network shares several important "building blocks" with CPGs that have been analyzed in other systems. 7. Muscarinic inputs are implicated as an important gastric regulator. We compare these responses with the reported modulatory actions of the anterior pyloric modulator (AMP), an identified, putatively cholinergic input interneuron that may act via muscarinic mechanisms. PMID- 1432056 TI - Changes in motor responses induced by cerebellar stimulation during classical forelimb flexion conditioning in cat. AB - 1. The ability of somaesthetic sensory inputs to produce structural changes in the connectivities of the central nervous structures involved in motor activity was tested with an alpha type of classical conditioning in chronically prepared adult cats. Repetitive sensory stimulation was applied at constant intervals after the activation of the motor circuits originating in the neurons or efferent axons of the cerebellar nuclei. A conditional stimulation (CS) applied to interpositus neurons was consistently paired with an unconditional stimulation (UCS) applied to the dorsal skin of the forelimb extremity to induce associative sensorimotor conditioning. The sites at which the conditional and unconditional stimuli were applied set up a simplified sensorimotor circuit including pathways transmitting both these stimuli and others mediating the expression of the conditioned responses. 2. To test the changes resulting from the conditioning, electrodes were implanted into the various relay structures on the cerebellar efferent pathways (ventrolateral nucleus motor cortex). The forelimb motor responses elicited by stimulating these relay structures were recorded with a potentiometer placed at the elbow joint. The angular displacement (amplitude) and latency of the responses and the percentage response rates were systematically quantified throughout the conditioning procedure and at test sessions carried out after the daily conditioning routines. 3. It was observed that daily repetition of paired CS-UCS led to an increase in the response rates and amplitudes of the forelimb flexions, which already began to occur very slightly on the first 4 or 5 days in response to the alpha conditioning, whereas the CS when applied alone failed to produce any changes in this initial response. Likewise, after the acquisition phase, repeated presentation of either the CS alone or the CS preceded by the UCS led to the extinction of the conditioned response, thus indicating that the observed changes were of an associative nature and that they depended on interactions between the motor and sensory inputs occurring somewhere in the CNS. In fact, the effects of conditioning were not generalized, but involved only a circumscribed circuit originating in the cerebellar neurons stimulated by the CS, which were activated concomitantly with the sensory pathways. 4. The conditioned response amplitudes were enhanced by 2.5-3 times their initial value. This enhancement persisted at the end of acquisition or after several days of consolidation, even when the paired CS-UCS sessions were interrupted for a period of 15 days to 2 mo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432057 TI - Mechanical response of frog saccular hair bundles to the aminoglycoside block of mechanoelectrical transduction. AB - 1. Deflections of the mechanosensory hair bundles on frog saccular hair cells were measured interferometrically, with submillisecond temporal and submicrometer spatial resolution, and with subnanometer displacement sensitivity. 2. The direction of the initial bundle deflection (toward the taller stereocilia) in response to a sudden application of aminoglycoside antibiotics shows that the mechanosensory channels are blocked in their mechanically open state. 3. The magnitude of the initial deflection is consistent with published data on the gating swing as derived from the gating compliance. 4. A delayed relaxation and frequently a reversal of the initial deflection were observed and are attributed to the previously reported mechanical adaptation mechanism, which is at least partially controlled by the influx of Ca2+ through the transduction channels. 5. Increases of low-frequency spontaneous motion were found at intermediate blocker concentrations. They can be well accounted for by the fluctuating force exerted on the bundle by the random binding and unbinding of blocker molecules. 6. The mechanical response of the hair bundle to aminoglycosides may be related to their acute and specific ototoxicity. PMID- 1432058 TI - Control of elevator muscle activity during simulated chewing with varying food resistance in humans. AB - 1. During chewing, a small part of the observed muscle activity is needed for the basic open-close movements of the mandible, and much additional muscle activity (AMA) is needed to overcome the resistance of the food. In chewing cycles in which a counteracting force is expected, the AMA is mainly generated by peripheral induction with a latency of approximately 23 ms. It was investigated whether an open-loop or closed-loop mechanism is involved in the control of the AMA in these cycles. 2. Subjects made rhythmic open-close movements at their natural chewing frequency controlled by a metronome. Food resistance was simulated by an external force, acting on the jaw in a downward direction during part of the closing movement. Sequences of cycles with a force were unexpectedly alternated with sequences of cycles with a different force. The force changed from 19 to 0 N and vice versa, and from 25 to 6 N and vice versa. Jaw movement and surface electromyogram of the masseter, temporalis, and suprahyoid muscles on both sides were recorded during cycles before and after the transition from one force condition to another. 3. The movement trajectory and AMA of the second and following cycles with a new force appeared to be similar. Thus adaptation to the changed circumstances occurred within two open-close cycles. 4. In the first cycle with 0 or 6 N in the 19----0 N and 25----6 N experiments respectively, a large part of the AMA had disappeared. The AMA in this cycle started to differ from the AMA in the previous cycle approximately 23 ms after the moment the force in this cycle started to differ from the previous cycle. 5. In the first cycle with 19 or 25 N in the reverse experiments, the AMA increased 120-136 ms after the moment the force in this cycle started to differ from the previous cycle. 6. During the closing phase of each open-close cycle, no muscle activity of the suprahyoid muscles was observed; thus co-contraction with the elevator muscles did not occur. 7. It was concluded that the AMA is under control of a closed-loop mechanism with a latency of approximately 23 ms. However, the reflex output has a maximum, depending on information about the food resistance gained in previous cycles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432059 TI - Neuronal activity in monkey striatum related to the expectation of predictable environmental events. AB - 1. This study investigated neuronal activity in the striatum preceding predictable environmental events and behavioral reactions. Monkeys performed in a delayed go-nogo task that included separate time periods during which animals expected signals of behavioral significance, prepared for execution or inhibition of arm reaching movements, and expected the delivery of reward. In the task, animals were instructed by a green light cue to perform an arm reaching movement when a trigger stimulus came on approximately 3 s later (go situation). Movement was withheld after the same trigger light when the instruction cue had been red (nogo situation). Liquid reward was delivered on correct performance in both situations. 2. A total of 1,173 neurons were studied in the striatum (caudate nucleus and putamen) of 3 animals, of which 615 (52%) showed some change in activity during task performance. This report describes how the activity of 193 task-related neurons increased in advance of at least 1 component of the task, namely the instruction cue, the trigger stimulus, or the delivery of liquid reward. These neurons were found in dorsal and anterior parts of caudate and putamen and were slightly more frequent in the proximity of the internal capsule. 3. The activity of 16 neurons increased in both go and nogo trials before the onset of the instruction and subsided shortly after this signal. These activations may be related to the expectation of the instruction as the first signal in each trial. 4. The activity of 15 neurons increased between the instruction and the trigger stimulus in both go and nogo trials. These activations may be related to the expectation of the trigger stimulus independent of an arm movement. Further 56 neurons showed sustained activations only when the instruction requested a movement reaction. Activations were absent in trials in which the movement was withheld. Twenty-one of these neurons were tested with 2 different movement targets, 5 of which showed activity related to the direction of movement. These activations may be related to the preparation of movement or expectation of the specific movement triggering signal. The activity of an additional 20 neurons was unmodulated before the trigger stimulus in movement trials but increased in the interval between the no-movement instruction and the trigger stimulus for withholding the movement. These activations may be related to the preparation of movement inhibition as specific nogo reaction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432060 TI - Activity-induced elevations of intracellular calcium concentration in pyramidal and nonpyramidal cells of the CA3 region of rat hippocampal slice cultures. AB - 1. Depolarization-induced elevations of intracellular calcium concentration ([Ca2+]i) were examined in slice-cultured hippocampal pyramidal and nonpyramidal cells of the CA3 region by combined intracellular and multisite fura-2 recording techniques. 2. In pyramidal cells, spiking activity induced by depolarizing current pulses (200-800 ms) induced transient elevations of somatic as well as of proximal dendritic [Ca2+]i. The calcium signals from the proximal dendrites were larger in amplitude and decayed much faster than those from the soma. Depolarization of presumed interneurons induced comparable somatic and dendritic calcium transients, which decayed faster than those observed in pyramidal cell somata. 3. The calcium transients of pyramidal cells, but not those of nonpyramidal cells, were associated with a slow afterhyperpolarization (sAHP), whose time course was correlated with that of the somatic calcium signal. We conclude that the lack of a sAHP in non-pyramidal cells cannot be explained by the absence of an efficient rise in [Ca2+]i but rather by the absence of the potassium conductance underlying the sAHP in pyramidal cells. PMID- 1432061 TI - Effective synaptic current can be estimated from measurements of neuronal discharge. AB - 1. The basic question of how motoneurons transform synaptic inputs into spike train outputs remains unresolved, despite detailed knowledge of their morphology, electrophysiology, and synaptic connectivity. We have approached this problem by making measurements of a synaptic input under steady-state conditions and combining them with quantitative assessments of their effects on the discharge rates of cat spinal motoneurons. 2. We used a modified voltage-clamp technique to measure the steady-state effective synaptic currents (IN) produced by rubrospinal input to cat triceps surae motoneurons. In the same motoneurons we measured the slope of the firing rate-injected current (f-i) relation in the primary range. We then reactivated the rubrospinal input during steady, repetitive firing to assess its effect on motoneuron discharge rate. 3. We found that changes in the steady state discharge rate of a motoneuron produced by this synaptic input could be described simply as the product of the net effective synaptic current measured at the soma and the slope of the motoneuron's f-i relation. This expression essentially redefines synaptic efficacy in terms of a cell's basic input-output function. Further, measurements of effective synaptic current simplify the task of estimating synaptic efficacy, because detailed knowledge of neither the electrotonic architecture of the postsynaptic cell nor of the locations of the presynaptic boutons is required. PMID- 1432062 TI - Primate premotor cortex: dissociation of visuomotor from sensory signals. AB - 1. If we assume adequate control for attention, memory, and stimulus location, a bona fide sensory response would be unaffected by whether a visuospatial stimulus instructs (1) one limb movement versus another or (2) limb movement versus a shift in spatial attention or memory. Two behavioral methods tested whether apparently sensory responses in the monkey's premotor cortex are strictly that, or, alternatively, whether they reflect the action instructed by a stimulus. 2. When an identical stimulus leads to two different responses, phasic discharge after a visuospatial stimulus is significantly, often dramatically, affected by the response. Similarly, premotor cortex neurons discharge more after a stimulus instructs a limb movement than after the same stimulus instructs a shift in spatial attention or memory. Thus, for the majority of premotor cortex neurons, the hypothesis that phasic poststimulus activity modulation represents a sensory response can be rejected. PMID- 1432063 TI - Bursting and tonic discharges in two classes of reticular thalamic neurons. AB - 1. Two types of cat reticular (RE) thalamic cells were disclosed by means of intracellular recordings under urethan anesthesia. The RE neurons were identified by their typical depolarizing spindle oscillations in response to synchronous stimulation of the internal capsule. 2. In type I neurons (n = 41), depolarizing current pulses induced tonic firing at the resting or slightly depolarized membrane potential (Vm) and triggered high-frequency spike bursts at a Vm more negative than -75 mV. As well, these cells discharged rebound bursts at the break of a hyperpolarizing current pulse. Internal capsule stimulation elicited spindle sequences made off by depolarizing waves giving rise to spike bursts. 3. Type II cells (n = 9) did not discharge spike bursts to large depolarizing current pulses even when the Vm reached -100 mV, nor did they fire rebound bursts after long lasting hyperpolarizing current pulses or spike bursts riding on the rhythmic depolarizing components of spindle sequences. 4. Compared with type I cells, type II cells showed less frequency accommodation during tonic firing. The latter neuronal class discharged at high frequencies (40 Hz) with slight DC depolarization, approximately 8-10 Hz at the resting Vm, and no underlying synaptic or subthreshold oscillatory events could be detected when the firing was blocked by DC hyperpolarization. 5. The presence of two cell classes in the RE nucleus challenges the common view that this nucleus consists of a single neuronal class. We suggest that a different set of conductances is present in type II RE neurons, thus preventing the low-threshold Ca2+ current from dominating the behavior of these cells. PMID- 1432064 TI - Responses of single facial taste fibers in the channel catfish, Ictalurus punctatus, to amino acids. AB - 1. Amino acids and nucleotides stimulate taste receptors of teleosts. In this report, responses to these compounds of 105 facial taste fibers (79 fully characterized) that innervate maxillary barbel taste buds of the channel catfish (Ictalurus punctatus) were analyzed. 2. The fully characterized facial taste fibers that responded to amino acids (n = 68) were generally poorly responsive to nucleotides and related substances (NRS), whereas the fibers responsive to NRS (n = 11) were poorly responsive to amino acids. Spike discharge of the amino acid responsive fibers to the most potent amino acid stimulus tested per fiber increased 44-fold from a mean spontaneous activity of 2.1 +/- 3.5 to 92.1 +/- 42.4 (SD) spikes/3 s. Spike activity of the NRS-responsive fibers to NRS increased 11.5-fold from a mean spontaneous activity of 3.4 +/- 5.9 to 39.1 +/- 27.4 spikes/3 s. There was no significant difference between the spontaneous rates, but stimulus evoked spike rates for the amino acid-responsive fibers were significantly greater (P < 0.05; Mann-Whitney test) than those for the NRS responsive fibers. 3. Hierarchical cluster analysis based on the 3-s response time identified three major groups of neurons. The identified clusters comprised neurons that were highly responsive to either L-alanine (i.e., Ala cluster; n = 39), L-arginine (i.e., Arg cluster; n = 29), or NRS (NRS cluster; n = 11). Fibers comprising the Arg cluster were more narrowly tuned than those within the Ala cluster. This report further characterizes the responses to amino acids of the individual facial taste fibers comprising the Ala and Arg clusters. 4. Subclusters were evident within both of the amino acid-responsive clusters. The Arg cluster was divisible into two subclusters dependent on the response to 1 mM L-proline. Twelve neurons that were significantly (P < 0.05; Mann-Whitney test) more responsive to L-proline than the remaining 17 neurons within the Arg cluster formed the Arg/Pro subcluster; these latter 17 neurons comprised the Arg subcluster. However, there was no significant difference (Mann-Whitney test) in the response to L-arginine between fibers within either subcluster across four different response times analyzed. Fibers within the Ala cluster were generally poorly responsive to L-proline. Four alanine subclusters were suggested on the basis of their relative responses to L-alanine, D-alanine, L-arginine, and the NRS; however, of the 39 fibers comprising the alanine cluster, two alanine subclusters comprised only two fibers each, and the third subcluster consisted of four fibers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432065 TI - Intravenous morphine-induced activation of vagal afferents: peripheral, spinal, and CNS substrates mediating inhibition of spinal nociception and cardiovascular responses. AB - 1. Intravenous administration of 1.0 mg/kg of morphine produces inhibition of the nociceptive tail-flick (TF) reflex, hypotension, and bradycardia in the pentobarbital-anesthetized rat. The present experiments examined peripheral, spinal, and supraspinal relays for inhibition of the TF reflex and cardiovascular responses produced by morphine (1.0 mg/kg iv) in the pentobarbital-anesthetized rat using 1) bilateral cervical vagotomy, 2) spinal cold block or mechanical lesions of the dorsolateral funiculi (DLFs), or 3) nonselective local anesthesia or soma-selective lesions of specific CNS regions. Intravenous morphine-induced inhibition of responses of unidentified, ascending, and spinothalamic tract (STT) lumbosacral spinal dorsal horn neurons to noxious heating of the hindpaw were also examined in intact and bilateral cervical vagotomized rats. 2. Bilateral cervical vagotomy significantly attenuated inhibition of the TF reflex and bradycardia produced by intravenous administration of morphine. Bilateral cervical vagogtomy changed the normal depressor response produced by morphine into a sustained pressor response. Inhibition of the TF reflex in intact rats was not due to changes in tail temperature. 3. Spinal cold block significantly attenuated inhibition of the TF reflex, the depressor response, and the bradycardia produced by intravenous administration of morphine. However, bilateral mechanical transections of the DLFs failed to significantly affect either inhibition of the TF reflex or cardiovascular responses produced by this dose of intravenous morphine. 4. Microinjection of either lidocaine or ibotenic acid into the nuclei tracti solitarii (NTS), rostromedial medulla (RMM), or ventrolateral pontine tegmentum (VLPT) attenuated morphine-induced inhibition of the TF reflex. Similar microinjections into either the periaqueductal gray (PAG) or the dorsolateral pons (DLP) failed to affect morphine-induced inhibition of the TF reflex. 5. Microinjection of either lidocaine or ibotenic acid into the NTS, RMM, VLPT, DLP, or rostral ventrolateral medulla (RVLM) attenuated the depressor response produced by morphine, although baseline arterial blood pressure (ABP) was affected by ibotenic acid microinjections in the DLP. In all these cases, the microinjections failed to reveal a sustained pressor response as was observed with bilateral cervical vagotomy. Similar microinjections into the PAG failed to affect the depressor response produced by morphine. 6. The lidocaine and ibotenic acid microinjection treatments also showed that the bradycardic response produced by morphine depends on the integrity of the NTS, RMM, RVLM, and possibly the DLP, but not the PAG or VLPT.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432066 TI - Influence of synaptic identity on single-Ia-afferent connectivity and EPSP amplitude in the adult cat: homonymous versus heteronymous connections. AB - 1. This study makes use of the pattern of synaptic connections between motoneurons and Ia afferents of triceps surae muscles in the cat to test the relative importance of synaptic identity, neuronal size, and neuronal topography as determinants of Ia-afferent connectivity and excitatory postsynaptic potential (EPSP) amplitude. 2. The synaptic actions of single-Ia medial gastrocnemius (MG) afferents were measured by intracellular recording in MG and lateral gastrocnemius (LG) motoneurons. The spike-triggered averaging technique was used to measure EPSPs generated by homonymous or heteronymous Ia afferents and motoneurons, i.e., neurons supplying the same or different muscles, respectively. In agreement with earlier studies, the pooled sample showed that the number of functional connections and the size of EPSPs were both significantly greater for homonymous than for heteronymous neurons. 3. Afferent conduction velocity, motoneuron conduction velocity, rheobase current, and position of the motoneuron relative to the spinal cord afferent entry were all correlated with EPSP amplitude, but the amplitude difference between homonymous and heteronymous connections remained significant after the statistical removal analysis of covariance (ANCOVA) of the contribution of these variables. Stepwise multiple regression analysis showed that synaptic identity explained the greatest fraction of the variance in EPSP amplitude (9%), with significant but smaller fractions accounted for by rheobase current or motoneuron conduction velocity. 4. In a separate experiment, the monosynaptic affects from both homonymous and heteronymous single-Ia afferents were examined in each of 88 MG or LG motoneurons. The single-Ia afferents used in this portion of the study were sampled from both MG and LG muscles and selected for similar conduction velocities and spinal cord entry points.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432067 TI - Differential sensitivity to bradykinin of esophageal distension-sensitive mechanoreceptors in vagal and sympathetic afferents of the opossum. AB - 1. Single-unit activity was recorded from afferent fibers in the cervical vagus and thoracic sympathetic nerves in the opossum. Seventy-six fibers that responded to balloon distension (100 mmHg for 10 s) of the smooth muscle portion of the esophagus were selected for further study. 2. Forty-nine distension-sensitive afferents were identified in the vagus nerve. The stimulus response function (SRF) of 41 fibers behaved as "low-threshold mechanoreceptors" (LTM), with mean threshold value of 0.29 +/- 0.17 mmHg and saturation pressure of 50-70 mmHg. All fibers demonstrated background activity, with a mean rate of 8.83 +/- 0.93 imp/s (range 0.5-31.25). 3. Twenty-seven distension-sensitive afferents were identified in the thoracic sympathetic chain (T6-T8) and splanchnic nerve. The SRF study revealed two types of fibers: 1) a wide-dynamic-range mechanonociceptor (WDRMN) with a mean response threshold of 3.43 +/- 0.90 mmHg (n = 15) and 2) a "high threshold mechanonociceptor" (HTMN) with a mean response threshold of 34.93 +/- 2.70 mmHg (n = 12). The mean background activities of WDRMN and HTMN fibers were 0.5 +/- 0.13 and 0.20 +/- 0.08 imp/s, respectively. Both of these fibers had saturation pressures of > 120 mmHg. 4. The conduction velocities were measured in 14 LTM, 10 WDRMN, and seven HTMN fibers. The mean conduction velocity of LTM fibers was 5.03 +/- 1.35 m/s (range 0.97-18.00), with five unmyelinated "C" fibers (< 2.5 m/s) and nine A-delta fibers (> 2.5 m/s). The mean conduction velocity of WDRMN fibers was 3.64 +/- 0.84 m/s (range 1.10-8.25), consisting of five C-fibers and five A-delta fibers. The mean conduction velocity of HTMN fibers was 6.22 +/- 2.35 m/s (range 1.73-24.66); three fibers were unmyelinated C fibers, and four fibers were A-delta fibers. 5. The sensitivity to bradykinin (BK) administered systemically (1-300 micrograms/kg) was tested in LTM (n = 34), WDRMN (n = 15), and HTMN (n = 8) fibers. Twenty-six (66%) LTM fibers responded to BK, and eight (34%) fibers were insensitive to BK. All 15 WDRMN and eight HTMN fibers tested responded to BK. 6. Tachyphylaxis to repeated application of BK was tested in all three classes of fibers. The vagal LTM fibers did not exhibit tachyphylaxis when BK was given at an intervals of 10 min. The sympathetic WDRMN and HTMN fibers demonstrated partial tachyphylaxis when BK was injected at 10-min intervals, but not when BK was injected at 20-min intervals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432068 TI - Force response of rat soleus muscle to variable-frequency train stimulation. AB - 1. The purpose of this study was to study the effects of a high-frequency burst of pulses at the onset of a subtetanic train of pulses on the force output of the rat soleus muscle. 2. The soleus muscle was studied in eight rats deeply anesthetized with urethan. The effects of two-, three-, or four-pulse bursts at the onset of subtetanic trains containing a total of 12 pulses were studied in detail. 3. The results showed that two-pulse bursts at the onset of the train produced approximately 20% augmentation in average force and nearly a 50% reduction in the time required to reach a targeted level of force, compared with a comparable 12-pulse subtetanic constant-frequency train; three- or four- pulse bursts produced progressively less additional improvement. In contrast, the two pulse bursts produced approximately 13% increase in the force-time integral (Area), the three-pulse burst did not significantly further increase the Area gain, and the use of four-pulse bursts markedly decreased the gain in Area. 4. For all three bursts, the observed force augmentation rapidly declined over the 12-pulse trains. Extrapolation beyond the actual data suggested that the force augmentation should last for between approximately 16 and 19 interpulse intervals. 5. To describe the characteristics of the contractile response of the muscle that explains or predicts the amount of force augmentation seen, we made three measurements of the response to the burst of pulses: 1) the peak force produced by the initial burst of pulses (PeakBURST), 2) the force at the time of arrival of the pulse that followed the burst (CatchBURST), and 3) the rise in force produced by the pulse that followed the burst (PotBURST). Of these three measurements, the CatchBURST was the best predictor of the force augmentation seen. 6. The present results showed 1) the importance of the stimulation pattern on the force output of skeletal muscle; 2) that the force-frequency relationship is multivalued, with force depending on both the stimulation history and stimulation frequency; and 3) that a relatively simple discharge strategy, where each train of pulses begins with one or two brief interpulse interval durations, will produce the maximum force from the muscle and result in a predictable force frequency relationship. PMID- 1432069 TI - Modulation of IK,Ca by phorbol ester-mediated activation of PKC in pleural sensory neurons of Aplysia. AB - 1. The electrophysiological properties of the sensory neurons that mediate withdrawal reflexes in Aplysia are modulated by a number of second messengers. For example, the second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and arachidonic acid modulate the S-K+ current (IK,S) and the calcium-activated K+ current (IK,Ca). Recent evidence suggests that protein kinase C (PKC) may also be an important regulator of cellular plasticity. In the present study we examined the possibility that IK,Ca was modulated by the activation of PKC in the pleural sensory neurons. 2. In voltage-clamped sensory neurons the application of phorbol esters, such as phorbol dibutyrate (PDBu), phorbol myristate (PMA), and phorbol diacetate (PDAc), which activate PKC, caused a dose-dependent increase in a voltage-dependent current with properties that resembled IK,Ca. The inactive isomer of phorbol ester, 4 alpha-phorbol, was without effect. 3. This phorbol ester-sensitive current had the kinetics and pharmacological sensitivity of IK,Ca. The current developed slowly during step depolarizations, showed little inactivation, and was activated at membrane potentials greater than approximately 0 mV. In addition, the current modulated by phorbol esters was blocked by a concentration of tetraethylammonium (TEA) that blocks a component of IK,Ca in the sensory neurons. 4. IK,Ca, which was activated directly by the iontophoretic injection of Ca2+, was also enhanced by PDBu. Moreover, the enhancement of Ca(2+) elicited responses by PDBu persisted after Ca2+ influx was blocked by cobalt. These results indicate that at least one component of the modulation of IK,Ca by PDBu was independent of the modulation of voltage-dependent Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432070 TI - Two-tone suppression in the basilar membrane of the cochlea: mechanical basis of auditory-nerve rate suppression. AB - 1. The vibratory response to two-tone stimuli was measured in the basilar membrane of the chinchilla cochlea by means of the Mossbauer technique or laser velocimetry. Measurements were made at sites with characteristic frequency (CF, the frequency at which an auditory structure is most sensitive) of 7-10 kHz, located approximately 3.5 mm from the oval window. 2. Two-tone suppression (reduction in the response to one tone due to the presence of another) was demonstrated for CF probe tones and suppressor tones with frequencies both higher and lower than CF, at moderately low stimulus levels, including probe-suppressor combinations for which responses to the suppressor were lower than responses to the probe tone alone. 3. For a fixed suppressor tone, suppression magnitude decreased as a function of increasing probe intensity. 4. The magnitude of suppression increased monotonically with suppressor intensity. 5. The rate of growth of suppression magnitude with suppressor intensity was higher for suppressors in the region below CF than for those in the region above CF. 6. For low-frequency suppressor tones, suppression magnitude varied periodically, attaining one or two maxima within each period of the suppressor tone. 7. Suppression was frequency tuned: for either above-CF or below-CF suppressor tones, suppression magnitude reached a maximum for probe frequencies near CF. 8. Cochlear damage or death diminished or abolished suppression. There was a clear positive correlation between magnitude of suppression and basilar-membrane sensitivity for responses to CF tones. 9. Suppression tended to be accompanied by small phase lags in responses to CF probe tones. 10. Because all of the features of two-tone suppression at the basilar membrane match qualitatively (and, generally, also quantitatively) the features of two-tone rate suppression in auditory-nerve fibers, it is concluded that neural two-tone rate suppression originates in mechanical phenomena at the basilar membrane. 11. Because the lability of mechanical suppression parallels the loss of sensitivity and frequency tuning due to outer hair cell dysfunction, the present findings suggest that mechanical two-tone suppression arises from an interaction between the outer hair cells and the basilar membrane. PMID- 1432071 TI - Parallel distributed network characteristics of the DSCT. AB - 1. We examined the functional organization of the dorsal spinocerebellar tract (DSCT) and found that it is similar to that of a parallel distributed network having widespread connectivity among parallel elements. The prevailing view is that the DSCT provides receptor-specific information to the cerebellum regarding muscle and cutaneous inputs from the hindlimbs, but that view does not consider the convergent inputs to DSCT neurons from multimodal polysynaptic pathways. 2. Spontaneously active DSCT neurons respond to peripheral stimulation with changes in their firing probability. We characterized the temporal patterns of poststimulus excitability changes for a large number of neurons using principal component analysis. The response of each neuron was represented by a response vector in three-dimensional principal component space, in which similar vectors represent responses having a similar waveform for their poststimulus activity patterns. 3. We compared the responses of large populations of DSCT units to two types of stimuli: small (3-8 deg) passive rotations of the foot at the ankle of an intact limb (234 cells) and stretch or contraction of an isolated muscle group (gastrocnemius-soleus, 168 cells). Most of the cells tested had significant responses (P < 0.05) to both types of stimuli (40-78% responded to muscle stimulation and 88% to foot rotation), and they exhibited similar patterns of poststimulus activity. Long-lasting inhibitory responses and excitatory responses with a range of peak times (< 10- > 60 ms) were prevalent in all cases. The population response to each stimulus was characterized by the relative incidence of response types among the units in a representative sample of the population. 4. The time course of excitability changes induced in DSCT cells by the stimuli could have been determined primarily by the presynaptic circuitry or by postsynaptic factors intrinsic to the DSCT cells. The evidence presented suggests that the selection of response waveforms and their distribution among the DSCT cells was determined presynaptically. We found that individual cells were capable of diverse responses to different stimuli. 5. Sample groups of 7-30 cells were selected at random and also on the basis of the similarity of their responses to one type of stimulus. The distributions of response types among the cells of the sample groups were compared to the distributions for the entire population recorded for each stimulus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432072 TI - Physiological properties of primate lumbar motoneurons. AB - 1. Intracellular recordings were obtained from 149 motoneurons innervating triceps surae (n = 109) and more distal muscles (n = 40) in 14 pentobarbital anesthetized monkeys (Macaca nemestrina). The variables evaluated were resting membrane potential, action potential amplitude, conduction velocity (CV), input resistance (RN), membrane time constant (tau m), electrotonic length (L), whole cell capacitance (Ctot), long current pulse threshold (rheobase), short current pulse threshold (Ishort), afterhyperpolarization (AHP) maximum amplitude (AHPmax), AHP duration (AHPdur), time to half maximum AHP amplitude (AHP t1/2), depolarization from resting potential to elicit action potential (Vdep), and threshold voltage for action potential discharge (Vthr). 2. Mean values +/- SD for the entire sample of motoneurons are as follows: resting membrane potential 67 +/- 6 mV; action potential amplitude 75 +/- 7 mV; CV 71 +/- 6 m/s; RN 1.0 +/- 0.5 M omega; tau m 4.4 +/- 1.5 ms; L 1.4 +/- 0.2 lambda; Ctot 7.1 +/- 1.8 nF; rheobase 13 +/- 7 nA; Ishort 29 +/- 14 nA; AHPmax 3.5 +/- 1.3 mV; AHPdur 77 +/- 26 ms; AHP t 1/2 21 +/- 7 ms; Vdep 11 +/- 4 mV; and Vthr -56 +/- 5 mV. CV is lower in soleus than in either medial or lateral gastrocnemius motoneurons, and RN is lower and tau m is longer in soleus than in lateral gastrocnemius motoneurons. 3. RN is higher in motoneurons with longer tau m and slower CV. A linear relationship exists between log(CV) and log(1/RN) with a slope of 1.8-2.2 (depending on the action potential amplitude acceptance criteria used), suggesting that membrane resistivity (Rm) does not vary systematically with cell size. 4. Rheobase is higher in motoneurons with lower RN, longer tau m, shorter AHP time course, and higher CV. Ishort and normalized rheobase (i.e., rheobase/Ctot) vary similarly with these motoneuron properties, except that Ishort is independent of tau m and normalized rheobase is independent of CV. 5. Vthr tends to be more depolarized in motoneurons with large Ctot, but the relationship is sufficiently weak so that any systematic variation in Vthr according to cell size probably contributes only minimally to recruitment order. Vthr does not vary systematically with CV, AHP time course, RN, or tau m. 6. Quantitative differences between macaque and cat triceps surae motoneurons are apparent in CV, which is slower in macaque than in cat, and to a lesser extent in tau m and RN, which are lower in macaque than in cat.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432073 TI - Kinetic properties of a transient outward current in rat neocortical neurons. AB - 1. Whole-cell patch-clamp techniques were used to record outward currents in embryonic rat neocortical neurons maintained in culture. In the presence of tetrodotoxin and cadmium, depolarization evoked an outward current with a complex waveform. This outward current consisted of an initial fast transient component and a late, slowly inactivating component. 2. The two outward current components could be separated pharmacologically with the use of tetraethylammonium (TEA) and 4-aminopyridine (4-AP). TEA (20 mM) applied extracellularly completely blocked the late component, unmasking a fast transient outward current (TOC). 4-AP (5 mM) applied extracellularly blocked the early component while reducing the late component by 27.8 +/- 9.7% (mean +/- SE). 3. The TOC activated after a short delay and rose rapidly to a peak. The time to peak was voltage dependent and decreased with depolarization. In the presence of 200 microM extracellular cadmium, activation threshold was around -25 mV, and current amplitude increased with depolarization. The voltage-conductance relationship was well fitted by the use of the Boltzmann equation with a Vm of +19 mV for half activation and a slope factor of +6 mV. 4. On sustained depolarization the TOC rapidly inactivated and decayed to baseline within 500-600 ms. The decay phase followed a single exponential time course with a time constant of 55-65 ms. The decay time was most rapid at potentials from +5 to +20 mV and increased slightly with further depolarization. 5. Steady-state inactivation of the TOC, in the presence of cadmium, was complete near -10 mV and was totally relieved at potentials more negative than -75 mV. With the use of the Boltzmann equation, a Vm of -34 mV for half inactivation and a slope factor of -8.6 mV were found. 6. Recovery of the TOC from steady-state inactivation followed a single exponential time course and was voltage dependent. When the membrane potential was held at -84 mV during the conditioning pulse, the time constant of recovery was 17 ms, increasing to 45.2 and 58.1 ms at holding potentials of -64 and -44 mV, respectively. Holding at potentials more negative than -84 mV produced no further change in the recovery time course. 7. The presence of 200 microM external cadmium altered the TOC activation and inactivation curves. Removal of cadmium produced a -16-mV shift in the Vm for half activation and a -25-mV shift in the inactivation curve. This sensitivity to cadmium is higher than that reported in other systems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432074 TI - Binaural interaction in the lateral superior olive: time difference sensitivity studied in mouse brain slice. AB - 1. The sensitivity of lateral superior olive (LSO) neurons to interaural time differences was examined in an in vitro brain slice preparation. Brain slices, 400-500 microns, were taken through the superior olivary complex of C57 BL/6J mice and were maintained in an oxygenated saline solution for single-unit recording. Both extracellular and intracellular recordings were made with glass pipettes filled with 4 M potassium acetate. Responses were elicited by applying current pulses to the trapezoid body through bipolar stimulating electrodes located ipsilateral or contralateral to the olivary complex. Binaural interactions were studied by manipulating the timing and intensity of paired ipsilateral and contralateral pulses. 2. In extracellular recordings, stimulation of the ipsilateral trapezoid body usually elicited a single action potential, whereas stimulation of the contralateral trapezoid body failed to produce a spike response. Bilateral stimulation resulted in the complete suppression of the evoked spike, indicating the presence of a contralateral inhibitory effect. The degree of inhibition depended on the interpulse interval between ipsilateral and contralateral stimulation. With sufficiently large ipsilateral lead times, the probability of eliciting an extracellular spike was 1.0. As the interpulse interval was gradually shifted to reduce the ipsilateral lead time, the response probability precipitously dropped to 0.0. Most neurons could be completely suppressed by simultaneous stimulation. The dynamic range, defined as the range of interpulse intervals over which response probability changed from 0.9 to 0.1, was between 125 and 225 microseconds for most cells tested. 3. With increasing contralateral lead times, the extracellularly recorded spike was eventually released from inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432075 TI - Axonal cross-excitation in nerve-end neuromas: comparison of A- and C-fibers. AB - 1. We recorded from single afferent axons ending in chronic sciatic nerve end neuromas in rats with the use of the teased-fiber method. Axons were sought that had ongoing impulse discharge originating in the neuroma. 2. Recording from myelinated (A-) fibers, tetanic stimulation of neighboring axons (50 Hz, 5 or 10 s, intensity adequate to drive A-fibers) caused an increase, and sometimes a decrease, in the rate of ongoing discharge in 68% of the fibers tested. In addition, some initially silent neuroma A-fibers (1.4%) were activated in this way. Both A beta and A delta fibers responded, although the likelihood of response was greater in A beta fibers. We call this form of interfiber cross excitation "crossed afterdischarge." 3. In contrast to A-fibers, crossed afterdischarge was evoked with these stimulation parameters in < or = 5% of the spontaneously active unmyelinated (C-) fibers sampled. No initially silent C fibers were activated. 4. C-fibers remained largely insensitive to cross excitation by neighboring axons even when the strength of stimulus pulses was increased so as to include neighboring A + C-fibers. 5. The difference between A- and C-fibers could not be accounted for on the basis of the maturity of the neuroma, rate and pattern of ongoing discharge, or use of Flaxedil paralysis. 6. The difference between A- and C-fibers is discussed in terms of two alternative mechanisms that may underlie crossed afterdischarge: mediation by a neurotransmitter(s) in a nonsynaptic mode, and mutual K+ depolarization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432077 TI - Evidence of input from lagged cells in the lateral geniculate nucleus to simple cells in cortical area 17 of the cat. AB - 1. The visual cortex receives several types of afferents from the lateral geniculate nucleus (LGN) of the thalamus. In the cat, previous work studied the ON/OFF and X/Y distinctions, investigating their convergence and segregation in cortex. Here we pursue the lagged/nonlagged dichotomy as it applies to simple cells in area 17. Lagged and nonlagged cells in the A-layers of the LGN can be distinguished by the timing of their responses to sinusoidally luminance modulated stimuli. We therefore used similar stimuli in cortex to search for signs of lagged and nonlagged inputs to cortical cells. 2. Line-weighting functions were obtained from 37 simple cells. A bar was presented at a series of positions across the receptive field, with the luminance of the bar modulated sinusoidally at a series of temporal frequencies. First harmonic response amplitude and phase values for each position were plotted as a function of temporal frequency. Linear regression on the phase versus temporal frequency data provided estimates of latency (slope) and absolute phase (intercept) for each receptive-field position tested. These two parameters were previously shown to distinguish between lagged and nonlagged LGN cells. Lagged cells generally have latencies > 100 ms and absolute phase lags; nonlagged cells have latencies < 100 ms and absolute phase leads. With the use of these criteria, we classified responses at discrete positions inside cortical receptive fields as lagged-like and nonlagged-like. 3. Both lagged-like and nonlagged-like responses were observed. The majority of cortical cells had only or nearly only nonlagged-like zones. In 15 of the 37 cells, however, the receptive field consisted of > or = 20% lagged-like zones. For eight of these cells, lagged-like responses predominated. 4. The distribution of latency and absolute phase across the sample of cortical simple cell receptive fields resembled the distribution for LGN cells. The resemblance was especially striking when only cells in or adjacent to geniculate recipient layers were considered. Absolute phase lags were almost uniformly associated with long latencies. Absolute phase leads were generally associated with short latencies, although cortical cells responded with long latencies and absolute phase leads slightly more often than LGN cells. 5. Cells in which a high percentage of lagged-like responses were observed had a restricted laminar localization, with all but two being found in layer 4B or 5A. Cells with predominantly nonlagged-like responses were found in all layers. 6. Lagged-like zones can not be easily explained as a result of stimulating combinations of nonlagged inputs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432076 TI - Calcium transients in cerebellar Purkinje neurons evoked by intracellular stimulation. AB - 1. Purkinje cells in thin slices from the guinea pig cerebellum were injected with fura-2 and high-speed sequences of fluorescence images from the cell body and entire dendritic tree were made while simultaneously recording somatic membrane potential during evoked and spontaneous electrical activity. The changes in fluorescence were interpreted in terms of changes in [Ca2+]i. 2. Individual calcium action potentials were usually accompanied by transient increases in [Ca2+]i all over the dendritic field. During evoked or spontaneous bursts of calcium spikes, [Ca2+]i increased more rapidly and to higher concentrations in fine dendrites than in thicker dendrites. At the end of a burst [Ca2+]i declined faster in thin dendrites than in thicker ones. These variations are most easily understood as deriving from the difference in surface-to-volume ratio of the two kinds of dendrites. 3. During bursts of calcium action potentials [Ca2+]i increases sometimes occurred only in individual dendritic branches, but always including the fine dendrites of that particular branch, showing that calcium action potentials can be regenerative in restrictive parts of the dendritic field without involving the soma or dendritic shaft. 4. Plateau or subthreshold potential changes evoked in the presence of tetrodotoxin (TTX) caused small, widespread increases in [Ca2+]i. The amplitude of these changes was much less than the increase corresponding to spike bursts. The distribution of these plateau Ca signals in thick and thin dendrites was similar to Ca spike-evoked signals, suggesting that the Ca conductances underlying these two potentials are the same or are distributed similarly in the dendrites. 5. Significant increases in [Ca2+]i in the soma were recorded during bursts of sodium-dependent action potentials in normal Ringer. Although much of this increase is due to calcium entry through calcium channels, some of this increase could be due to calcium entry through sodium channels. PMID- 1432078 TI - Strong heat stimulation sensitizes the heat response as well as the bradykinin response of visceral polymodal receptors. AB - 1. Hyperalgesia after thermal injury is a common phenomenon, but its mechanism is poorly understood. As a step toward understanding the mechanism for heat sensitization, we searched conditions that would induce sensitization consistently and studied changes in polymodal receptors in their responses to heat (45 and 48 degrees C) and to bradykinin. Experiments were conducted in vitro, with the use of testis-superior spermatic nerve preparations excised from anesthetized dogs. 2. Stimulation at 55 degrees C for 30 s induced clear augmentation of the responses to stimulations at 45 and 48 degrees C when tested within 10 min in 22 out of 24 testicular polymodal units. In the remaining two units, weak or delayed augmenting tendencies were observed. The response to stimulation at 45 degrees C increased from 0.28 +/- 0.08 to 2.99 +/- 0.46 (SE) imp/s, whereas at 48 degrees C it increased from 1.08 +/- 0.16 to 4.60 +/- 0.63 imp/s (P < 0.001, n = 24). A low-level ongoing discharge appeared in about one half of the units studied. 3. Despite frequent rinsing of the receptive field, augmentation of the heat response observed after stimulation at 55 degrees C continued for up to approximately 3 h. 4. The response to bradykinin (94 nM) was also potentiated: the net mean discharge rate (NMDR) during a 1-min application period of bradykinin as well as the total number of impulses induced by one bradykinin application significantly increased from 0.91 +/- 0.27 to 1.97 +/- 0.32 imp/s and from 213.9 +/- 42.3 to 433.5 +/- 58.7 impulses, respectively (P < 0.001, n = 15).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432079 TI - Neural interaction in cat primary auditory cortex. Dependence on recording depth, electrode separation, and age. AB - 1. Neural activity was recorded with two independent electrodes separated by 0.5 2 mm, aligned in parallel, and advanced perpendicular to the surface of the cat auditory cortex. For smaller separations a solid-state multielectrode array with interelectrode distances of 125 microns was used. The difference in recording depths for the two independently movable electrodes was never more than 100 microns; the electrode contacts of the multielectrode array were at the same depth. Thus the correlation studies dominantly explored horizontal interactions. 2. Out of 995 neuron pairs recorded, 478 represented pairs of single units, whereas the other pairs were contaminated with 5-10% misclassified spikes. Only the single-unit pairs were further analyzed. Of those pairs, 338 showed a clear correlation peak, and in 329 of these the peak heights were exceeding the Z > 4 significance level (P < 0.0001). Two hundred fifty-two of the significant correlograms (53% of total) could be attributed to common input; the remaining (16% of total) were indicative of unilateral excitation. For the 181 single electrode pairs the percentage of unilateral excitation pairs (42%) was about the same as the percentage of common input pairs (38%). For the 297 dual-electrode pairs all but one of the 184 significant correlations were indicative of common input. No correlograms indicative of inhibition were found. 3. The correlograms with clear peaks were classified into three types: narrow (n = 40), mixed (n = 77), and broad (n = 221). Narrow and mixed types were with two exceptions found only for single-electrode pairs; broad types were found for single- and dual electrode pairs. Narrow-type correlograms were in majority of the unilateral excitation type. Correlograms were calculated both for 1-ms binwidths (50-ms lead/lag time) and for 10-ms binwidth (500-ms lead/lag time). The correlograms were characterized by four parameters; the half width of the central peak, the peak correlation coefficient, the association index, and for unilateral excitation cases also by the effectiveness. 4. Across all three correlogram types the half width of the correlation peaks was significantly smaller for single electrode pairs (mean, 27 ms) than for dual-electrode pairs (mean, 42 ms). For broad-type correlograms only, the mean half widths were not significantly different between single- and dual-electrode pairs. 5. The correlation coefficients (1-ms bin correlograms) were significantly larger for single electrode pairs (mean, 0.038) than for dual-electrode pairs (mean, 0.011). The same was found for the 10-ms binwidth correlograms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432081 TI - Acuity-sensitivity trade-offs of X and Y cells in the cat lateral geniculate complex: role of the medial interlaminar nucleus in scotopic vision. AB - 1. The cat medial interlaminar nucleus (MIN) receives inputs almost exclusively from tapetal retina, suggesting that the MIN has a special role in dim-light vision. In this study we compared the sensitivities of cells in the MIN with those in layers A and magnocellular C of the lateral geniculate nucleus (LGNd), using drifting sinusoidal gratings to determine contrast thresholds as a function of spatial frequency and retinal adaptation level over the entire scotopic range. 2. About one-half of the cells recorded in the MIN and layer A had brisk responses that could be nulled by properly positioned, counterphased sinusoidal gratings, and were classified as X cells. The rest of the cells in the MIN and layer A, as well as all cells recorded in layer C, were Y cells. 3. MIN cells had higher contrast sensitivity than layer A cells for low spatial frequencies (0.15 cycles/deg and below) over a wide range of adaptation levels, both overall and for separate comparisons within X or Y cells. Layer C Y cells were intermediate in sensitivity between MIN and layer A Y cells. For low spatial frequencies, Y cells as a group were more sensitive than X cells, whereas the reverse was true for high spatial frequencies. 4. These data enable one to determine the lowest adaptation level at which stimuli of a given contrast can be detected for a given structure. At the lowest spatial frequencies, the MIN can function at adaptation levels approximately 1 log unit below layer A, averaged over all stimulus contrasts. In contrast, the tapetum lowers luminance threshold by at most 0.16 log unit. 5. For scotopic conditions and eccentricities within 15 degrees of the area centralis, contrast sensitivity decreases with eccentricity for low spatial frequencies and remains flat or slightly increases for high spatial frequencies. This relationship, which is opposite to that found for photopic vision, is strongest for MIN Y cells. 6. These data support the hypothesis that the retinal conflict between sensitivity and acuity is ameliorated in the CNS through separate thalamic relays with different degrees of afferent convergence. MIN cells have higher luminance sensitivity than layer A cells, but at the expense of acuity. Layer C appears to occupy an intermediate position in this trade-off. PMID- 1432080 TI - Ca(2+)-independent and Ca(2+)-dependent stimulation of quantal neurosecretion in avian ciliary ganglion neurons. AB - 1. Although it is generally agreed that Ca2+ couples depolarization to the release of neurotransmitters, hypertonic saline and ethanol (ETOH) evoke neurosecretion independent of extracellular Ca2+. One possible explanation is that these agents release Ca2+ from an intracellular store that then stimulates Ca(2+)-dependent neurosecretion. An alternative explanation is that these agents act independently of Ca2+. 2. This work extends previous observations on the action of ETOH and hypertonic solutions (HOSM) on neurons to include effects on [Ca2+]i. We have looked for Ca(2+)-independent or -dependent neurosecretion evoked by these agents in parasympathetic postganglionic neurons dissociated from chick ciliary ganglia and maintained in tissue culture. The change in concentration of free Ca2+ in the micromolar range inside neurons ([Ca2+]i) was measured with indo-1 with the use of a Meridian ACAS 470 laser scanning microspectrophotometer. 3. Elevated concentration of extracellular KCl increased [Ca2+]i and the frequency of quantal events. Also, a twofold increase in osmotic pressure (HOSM) produced a similar increase in quantal release and a significant rise in [Ca2+]i; however, the Ca2+ appeared to come from intracellular stores. 4. In contrast, ETOH stimulated quantal neurosecretion without a measurable change in [Ca2+]i. It appears the alcohol exerts its influence on some stage in the process of exocytosis that is distal to or independent of the site of Ca2+ action. 5. The effects of high [KCl]o and osmotic pressure were occlusive. This is explained in part by the observation that hypertonicity reduced Ca2+ current, but an action on Ca2+ stores is also likely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432082 TI - Dynamics and efficacy of saccade-facilitated vergence eye movements in monkeys. AB - 1. Four macaque monkeys were trained to fixate visual targets. Eye movements were recorded binocularly using the search coil technique. Saccades, vergence movements, and combinations of the two were elicited by training the monkeys to alternate the gaze between real visual targets that differed in viewing distance and eccentricity with respect to the monkeys' heads. 2. When they shifted the gaze between targets that were at different viewing distances, the monkeys made vergence eye movements. For targets placed along the midsagittal plane, the monkeys often made binocularly symmetric vergence movements. The peak speed of symmetric divergence movements increased linearly with vergence amplitude by 5.7 deg/s per degree of vergence. The peak speed of symmetric convergence movements increased linearly with vergence amplitude by 7.9 deg/s per degree of vergence. 3. For gaze shifts between targets placed eccentrically with respect to the midsagittal plane and at different viewing distances, the monkeys made saccades in combination with vergence eye movements. When a saccade occurred during a vergence movement, peak vergence eye speed increased abruptly and reached a peak that was proportional to the speed of the saccade. For four monkeys, peak divergence speed ranged from 242 to 315 deg/s and peak convergence speed ranged from 257 to 340 deg/s for 16-deg vergence and 20-deg saccadic eye movements. 4. For gaze shifts between far targets at the same viewing distance but different eccentricities, saccadic eye movements were transiently disjunctive even though there was no vergence requirement. Initially, the eyes diverged and then converged to restore fixation to the correct depth plane. Divergence was followed by convergence regardless of the direction of the saccade. 5. The presence of transient saccade-related disjunctive eye movements suggested that the abrupt increase in peak vergence speed during combined saccadic and vergence eye movements was produced by the linear addition of a vergence eye movement and the saccade-related transients. Consistent with this hypothesis, the rate of change in peak vergence speed during various-sized saccades between far targets (no vergence required) was similar to the rate of change in peak vergence speed during combined saccadic and vergence movements. However, the peak vergence speeds during the combined movements were higher than predicted by the linear addition hypothesis, suggesting the presence of an additional mechanism. 6. The saccade-related increase in peak vergence speed during combined saccades and vergences led to a significant decrease in the amount of time required to complete vergence movements.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432083 TI - Proportional enlargement of motor units after partial denervation of cat triceps surae muscles. AB - 1. To determine the capacity of motoneurons to increase their motor unit (MU) size by collateral sprouting and to assess this capacity in relation to the size of the motor nerve, we partially denervated soleus, lateral gastrocnemius (LG), and medial gastrocnemius (MG) muscles in adult and neonatal cats. Isometric force and extracellular nerve potentials were recorded from > or = 7% of the remaining MUs, 2.5-18 mo later. S1 or L7 roots were sectioned unilaterally and the number of remaining MUs was quantified by use of charge and force measurements. 2. The mean unit force increased inversely with MU number in partially denervated muscles, but the increase was less than predicted for extensive denervations (> or = 90%). The same enlargement of MU size occurred whether muscles were partially denervated in neonatal or adult animals. 3. The force distribution of MUs in partially denervated muscles was similar to normal but was shifted to larger force values in direct proportion to the extent of partial denervation (PD). All MUs increased in size by the same factor to preserve the normal force distribution. 4. Normal size relationships among force, contractile speed, and axon potential amplitude were observed for MUs in partially denervated muscles. Because changes in muscle fiber size could not account for the increase in unit force, these data show that increase in MU size, with respect to unit force and innervation ratio (muscle fibers per motoneuron), is proportional to the size of the motor nerve. 5. Enlargement of MU size in partially denervated muscles did not have a retrograde effect on nerve fiber caliber because axon potential amplitude and conduction velocity were not changed after PD. 6. Under conditions of extensive PD (> 85%), regenerated nerves from the cut spinal root reinnervated the gastrocnemius muscles. It is likely that nerves supplied muscle fibers that were not innervated by sprouts from nerves in the uncut root as well as displacing sprouts from terminals in extensively enlarged MUs. 7. We conclude that all motoneurons within a motor pool compensate for partial nerve injuries by collateral sprouting and that enlargement of MU size is a function of motor nerve size, consistent with Henneman's size principle. PMID- 1432084 TI - Role of inferior temporal neurons in visual memory. I. Temporal encoding of information about visual images, recalled images, and behavioral context. AB - 1. Lesions of the inferior temporal (IT) cortex selectively hamper monkeys in tasks requiring visual memory. A system that recognizes images must be able to encode a current stimulus, recall the code of a previous stimulus, compare the codes of the two stimuli, and make a decision on the basis of the outcome of the comparison. Therefore, IT neurons must be involved in at least one of these processes. To determine the specific role of IT neurons in visual memory, we measured the information conveyed in the neuronal responses about current patterns, recalled patterns, and behavioral context. 2. Two monkeys were trained to perform a sequential matching task using a set of 32 black and white Walsh patterns. In the course of an experiment, each pattern was presented repeatedly in sample, match, and nonmatch behavioral contexts. While the monkeys were performing the task, we recorded the activity of 76 neurons from area TE of IT. The neuronal responses to the stimuli were converted to spike density functions, and the resultant waveforms were quantified using their principal components. The relationships between the responses and the stimuli were studied using analysis of variance and information theory. 3. The analysis of variance was applied to the neuronal response waveforms using the context (sample, match, or nonmatch) and the patterns of the stimuli as independent variables and the spike count or the coefficients of the principal components as the dependent variables. We found that the waveforms of most neurons were significantly modulated by both the pattern and the context of the stimulus presentation. 4. We also analyzed the stimulus-response relationships using information theory. The input codes were based on the pattern and context of the stimuli, and the output codes were based on the spike count or the principal components of the responses. The neuronal response waveforms were found to convey significant amounts of information about both the pattern and context of the stimuli. Transmitted information was greatest when the response of a neuron was interpreted as a message about the combination of pattern and context. Nevertheless, there was information about context independent of pattern and vice versa. 5. We also used information theory to determine whether the neuronal responses to the second, or test, stimulus conveyed information about the pattern of the first, or sample, stimulus. The input codes were based on the patterns of the sample stimuli, and the output codes were based on the responses to the nonmatch test stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432085 TI - Role of inferior temporal neurons in visual memory. II. Multiplying temporal waveforms related to vision and memory. AB - 1. In the companion paper we reported on the activity of neurons in the inferior temporal (IT) cortex during a sequential pattern matching task. In this task a sample stimulus was followed by a test stimulus that was either a match or a nonmatch. Many of the neurons encoded information about the patterns of both current and previous stimuli in the temporal modulation of their responses. 2. A simple information processing model of visual memory can be formed with just four steps: 1) encode the current stimulus; 2) recall the code of a remembered stimulus; 3) compare the two codes; 4) and decide whether they are similar or different. The analysis presented in the first paper suggested that some IT neurons were performing the comparison step of visual memory. 3. We propose that IT neurons participate in the comparison of temporal waveforms related to vision and memory by multiplying them together. This product could form the basis of a crosscorrelation-based comparison. 4. We tested our hypothesis by fitting a simple multiplicative model to data from IT neurons. The model generated waveforms in separate memory and visual channels. The waveforms arising from the two channels were then multiplied on a point by point basis to yield the output waveform. The model was fitted to the actual neuronal data by a gradient descent method to find the best fit waveforms that also had the lowest total energy. 5. The multiplicative model fit the neuronal responses quite well. The multiplicative model made consistently better predictions of the actual response waveforms than did an additive model. Furthermore, the fit was better when the actual relationship between the responses and the sample and test stimuli were preserved than when that relationship was randomized. 6. We infer from the superior fit of the multiplicative model that IT neurons are multiplying temporally modulated waveforms arising from separate visual and memory systems in the comparison step of visual memory. PMID- 1432086 TI - Electrophysiology of the mammillary complex in vitro. II. Medial mammillary neurons. AB - 1. The electrophysiological properties of guinea pig medial mammillary body (MMB) neurons were studied using an in vitro slice preparation. 2. The neurons (n = 80) had an average resting potential of -57 +/- 5.5 (SD) mV, an input resistance of 176 +/- 83 M omega, and a spike amplitude of 58 +/- 15.7 mV. Most of the neurons were silent at rest (n = 52), but some fired spontaneous single spikes (n = 16) or spike bursts (n = 14). 3. The main electrophysiological characteristic of MMB neurons was the ability to generate Ca(2+)-dependent regenerative events, which resulted in very robust burst responses. However, this regenerative event was not the same for all neurons, ranging from typical low-threshold Ca2+ spikes (LTSs) to intermediate-threshold plateau potentials (ITPs). 4. The ITPs were distinct from the LTSs in that they lasted > or = 100 ms and were not inactivated at membrane potentials at or positive to -55 mV. 5. Some cells with a prominent ITP and no LTS (n = 36) displayed repetitive, usually rhythmic, bursting (n = 14). This ITP could be powerful enough to maintain rhythmic membrane potential oscillations after pharmacological block of Na+ conductances. 6. A group of 32 MMB neurons displayed complex bursting that was generated by activation of both LTSs and ITPs. This was established on the basis of their distinct time- and voltage-dependent characteristics. In a group of neurons (n = 14), the burst responses were exclusively generated by an LTS; however, a Ca(2+)-dependent plateau potential contributed to the generation of rebound-triggered oscillatory firing. 7. In addition to the Ca(2+)-dependent LTS and/or ITP, MMB neurons always displayed high-threshold Ca2+ spikes after reduction of K+ conductances with tetraethylammonium. 8. MMB neurons display one of the richer varieties of voltage dependent Ca2+ conductances so far encountered in mammalian CNS. We propose that the very prominent endogenous bursting and oscillatory properties of MB neurons allow this nuclear complex to function as an oscillatory relay for the transmission of low-frequency rhythmic activities throughout the limbic circuit. PMID- 1432087 TI - Visual response latencies in striate cortex of the macaque monkey. AB - 1. Many lines of evidence suggest that signals relayed by the magnocellular and parvocellular subdivisions of the primate lateral geniculate nucleus (LGN) maintain their segregation in cortical processing. We have examined two response properties of units in the striate cortex of macaque monkeys, latency and transience, with the goal of assessing whether they might be used to infer specific geniculate contributions. Recordings were made from 298 isolated units and 1,129 multiunit sites in the striate cortex in four monkeys. Excitotoxin lesions that selectively affected one or the other LGN subdivision were made in three animals to demonstrate directly the magnocellular and parvocellular contributions. An additional 435 single units and 551 multiunit sites were recorded after the ablations. 2. Most units in striate cortex had visual response latencies in the range of 30-50 ms under the stimulus conditions used. The earliest neuronal responses in striate cortex differed appreciably between individuals. The shortest latency recorded in the four animals ranged from 20 to 31 ms. Comparable values were obtained from both single unit and multiunit sites. After lesions were made in the magnocellular subdivision of the LGN in two animals, the shortest response latencies were 7 and 10 ms later than before the ablations. A larger lesion in the parvocellular subdivision of another animal produced no such shift. Thus it appears that the first 7-10 ms of cortical activation can be attributed to activation relayed by the magnocellular layers of the LGN. 3. The units with the shortest latencies were all found in layers 4C or 6 and their responses were among the most transient in striate cortex. Furthermore, their responses all showed a pronounced periodicity at a frequency of 50-100 Hz. This periodicity was stimulus locked, and the responses of all short-latency units oscillated in phase. 4. An index of response transience was computed for the units recorded in striate cortex. The distribution of this index was unimodal and gave no suggestion of distinct contributions from the geniculate subdivisions. Magnocellular and the parvocellular lesions affected the overall transience of responses in striate cortex. The changes, however, were very small; extremely transient responses and extremely sustained responses survived both types of lesions. 5. A characteristic profile was observed in the response latencies in superficial layers. Latencies appeared to increase monotonically from layer 4 toward the surface of cortex, with the most superficial neurons not becoming active until 15 ms after responses were observed in layer 4C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432088 TI - Flow of excitation within rat barrel cortex on striking a single vibrissa. AB - 1. Extracellular spike recordings were made from single cells in various layers of barrel cortex in adult rats anesthetized with urethan. Response magnitude and latency differences to brief 1.14 degrees deflections of mystacial vibrissae of center (principal) and surround receptive-field vibrissae were measured. Latency differences for pairs of cells in the same penetration to stimulation of the principal vibrissa were also collected. In separate experiments the domains of layer IV cells were mapped for their influence by a single vibrissa and their latencies to this vibrissa were recorded. In all experiments precise locations of layer IV cells in each penetration were identified using dye-lesioning and cytochrome oxidase staining of tangential sections. 2. The results suggest that principal vibrissa data are relayed radially in a column of neurons before parallel relay to adjacent columns. To the principal vibrissa, layers IV and Vb neurons discharged earliest, with layers II and III on average 2 and 3 ms later, respectively. Serial relay from layers IV to III to II was suggested to be the most common event. Although layer Va cells fired next, a single-column organization is not suggested for them because differences in latency or response magnitude to their principal and immediate surround vibrissae were not significant. Layer II, III and IV cells showed no statistical difference in latency to the nearest surround vibrissa but fired significantly later than to their principal input. 3. Because, from our previous studies, surround receptive fields of barrel cells in rat S1 cortex appear to be constructed intracortically, these data suggest a parallel column-column relay for their construction. Horizontal relay between barrels occurred first within the septae between barrels. Mean intracortical transmission velocities were calculated at approximately 0.05 m/s for column-column information transfer. PMID- 1432089 TI - Interpretation of time constant and electrotonic length estimates in multicylinder or branched neuronal structures. AB - 1. We have investigated the theoretical and practical problems associated with the interpretation of time constants and the estimation of electrotonic length with equivalent cylinder formulas for neurons best represented as multiple cylinders or branched structures. Two analytic methods were used to compute the time constants and coefficients of passive voltage transients (and time constants of current transients under voltage clamp). One method, suitable for simple geometries, involves analytic solutions to boundary value problems. The other, suitable for neurons of any geometric complexity, is an algebraic approach based on compartmental models. Neither of these methods requires the simulation of transients. 2. We computed the time constants and coefficients of voltage transients for several hypothetical neurons and also for a spinal motoneuron whose morphology was characterized from serial reconstructions. These time constants and coefficients were used to generate voltage transients. Then exponential peeling, nonlinear regression, and transform methods were applied to these transients to test how well these procedures estimate the underlying time constants and coefficients. 3. For a serially reconstructed motoneuron with 732 compartments, we found that the theoretical and peeled tau 0 values were nearly equal, but the theoretical tau 1 was much larger than the peeled tau 1. The theoretical tau 1 could not be peeled because it was associated with a coefficient, C1, that had a very small value. In fact, there were 156 time constants between 1.0 and 6.0 ms, most of which had very small coefficients; none had a coefficient larger than 2% of the signal. The peeled value of tau 1 (called tau 1 peel) can be viewed as some sort of a weighted average of the time constants having the largest coefficients. 4. We studied simple hypothetical neurons to determine what interpretation could be applied to the multitude of theoretical time constants. We found that after tau 0, there was a group of time constants associated with eigenfunctions that were odd (or approximately odd) functions with respect to the soma. These time constants could be interpreted as "equalizing" time constants along particular paths between different pairs of dendritic terminals in the neuron. After this group of time constants, there was one that we call tau even because it was associated with an eigen-function that was approximately even with respect to the soma. This tau even could be interpreted as an equalizing time constant for charge equalization between proximal membrane (soma and proximal dendrites) and distal membrane (including all distal dendrites).4= PMID- 1432090 TI - Electrotonic length estimates in neurons with dendritic tapering or somatic shunt. AB - 1. Compartmental models were used to compute the time constants and coefficients of voltage and current transients in hypothetical neurons having tapering dendrites or soma shunt and in a serially reconstructed motoneuron with soma shunt. These time constants and coefficients were used in equivalent cylinder formulas for the electrotonic length, L, of a cell to assess the magnitude of the errors that result when the equivalent cylinder formulas are applied to neurons with dendritic tapering or soma shunt. 2. Of all the formulas for a cylinder (with sealed ends), the most commonly used formula, which we call L tau 0/tau 1 (the formula uses the current-clamp time constants tau 0 and tau 1), was the most robust estimator of L in structures that tapered linearly. When the diameter at the end of the cylinder was no less than 20% of the initial diameter, L tau 0/tau 1 underestimated the actual L by at most 10%. 3. The equivalent cylinder formulas for a cylinder were applied to neurons modeled as a cylinder with a shunted soma at one end. The formula for L based solely on voltage-clamp time constants gave an exact estimate of L. However, the second voltage-clamp time constant cannot be reliably obtained experimentally for neurons studied thus far. Of the remaining formulas, L tau 0/tau 1 was again the most robust estimator of L. This formula overestimated L with the size of the overestimates depending on beta, rho beta = 1, and the actual L of the cylinder, where beta is the soma shunt factor, and rho beta = 1 is the dendritic-to-somatic conductance ratio when beta = 1 (no shunt). When the actual L was 0.5 and the soma shunt was large, this formula overestimated L by two- to threefold, but when the actual L was 1.5, the overestimate was only 10-15% regardless of the size of the shunt. 4. In neurons modeled as two cylinders with soma shunt, the L tau 0/tau 1 value computed with the actual tau 0 and tau 1 values overestimated the average L by two to six times when soma shunt was large. However, the L tau 0/tau 1 estimates computed with tau 0 and tau 1 values estimated with the exponential fitting program DISCRETE from voltage transients computed for these neuron models were never this large because of inherent problems in estimating closely spaced time constants from data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432091 TI - Estimating the electrotonic structure of neurons with compartmental models. AB - 1. A procedure based on compartmental modeling called the "constrained inverse computation" was developed for estimating the electrotonic structure of neurons. With the constrained inverse computation, a set of N electrotonic parameters are estimated iteratively with use of a Newton-Raphson algorithm given values of N parameters that can be measured or estimated from experimental data. 2. The constrained inverse computation is illustrated by several applications to the basic example of a neuron represented as one cylinder coupled to a soma. The number of unknown parameters estimated was different (ranging from 2 to 6) when different sets of constraints were chosen. The unknowns were chosen from the following: dendritic membrane resistivity Rmd, soma membrane resistivity Rms, intracellular resistivity Ri, membrane capacity Cm, dendritic membrane area AD, soma membrane area As, electrotonic length L, and resistivity-free length, rfl (rfl = 2l/d1/2 where l and d are length and diameter of the cylinder). The values of the unknown parameters were estimated from the values of an equal number of known parameters, which were chosen from the following: the time constants and coefficients of a voltage transient tau 0, tau 1, ..., C0, C1, ..., voltage-clamp time constants tau vc1, tau vc2, ..., and input resistance RN. Note that initially, morphological data were treated as unknown, rather than known. 3. When complete morphology was not known, parameters from voltage and current transients, combined with the input resistance were not sufficient to completely specify the electrotonic structure of the neuron. For a neuron represented as a cylinder coupled to a soma, there were an infinite number of combinations of Rmd, Rms, Ri, Cm, AS, AD, and L that could be fitted to the same voltage and current transients and input resistance. 4. One reason for the nonuniqueness when complete morphology was not specified is that the Ri estimate is intrinsically bound to the morphology. Ri enters the inverse computation only in the calculation of the electrotonic length of a compartment. The electrotonic length of a compartment is l[4 Ri/(dRmd)]1/2, where l and d are the length and diameter of the compartment. Without complete morphology, the inverse computation cannot distinguish between a change in d or l and a change in Ri. Even when morphology is known, the accuracy of the Ri estimate obtained by any fitting procedure is affected by systematic errors in length and diameter measurements (i.e., tissue shrinkage); the Ri estimate is inversely proportional to the length measurement and proportional to the square root of the diameter measurement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432092 TI - Role of metabotropic glutamate (ACPD) receptors at the parallel fiber-Purkinje cell synapse. AB - 1. The role of metabotropic glutamate receptors at the parallel fiber (PF) Purkinje cell synapse in cerebellum was studied by examining the actions of the active stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [1S,3R-ACPD (25-50 microM)] on fura-2-loaded, patch-clamped rat Purkinje cells in thin slices. 2. The bath application of 1S,3R-ACPD evoked a direct post-synaptic depolarization that readily desensitized during prolonged (> 1 min) applications of the drug. This depolarizing response to 1S,3R-ACPD differed from the slow depolarization to 1S,3R-ACPD observed in cortical neurons mediated via closure of potassium channels in that it was not associated with an obvious change in membrane conductance and was not blocked by external barium. Similarly, slow inward rectifier currents were not affected during the 1S,3R-ACPD-induced depolarization. 3. The direct depolarization induced by 1S,3R-ACPD was not mediated by N-methyl-D-aspartate (NMDA) or (RS)-alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid kainate (AMPA)-KA excitatory amino acid (EAA) receptor subtypes, because the response was not blocked in the presence of antagonists of these receptors. 4. The EAA antagonist L-2-amino-3-phosphonopropionic acid, which blocks 1S,3R-ACPD-induced inositide synthesis in other cell types, had no effect on the depolarizing response. 5. Fura-2 measurements of somatic [Ca2+]i revealed that [Ca2+]i was not elevated during the 1S,3R-ACPD-induced depolarization unless the cell fired calcium-dependent action potentials. 6. In addition to the direct depolarization induced by 1S,3R-ACPD, the amplitude of PF-evoked excitatory postsynaptic potentials (EPSPs) was profoundly and reversibly reduced. This effect was observed in all cells regardless of whether a direct depolarization was produced by 1S,3R-ACPD. This reduction of the PF EPSP generally preceded the onset of depolarizing responses, did not desensitize during prolonged applications of 1S,3R-ACPD, and was reversible. 7. The reversible reduction of the PF EPSP by 1S,3R-ACPD was not related to a postsynaptic blocking action of the drug, because responses of Purkinje cells to AMPA, an agonist of the EAA receptor subtype mediating the EPSP, were reversibly potentiated in the presence of 1S,3R-ACPD. 8. The nitric oxide synthesis promoter sodium nitroprusside (1-3 nM) had no effect on the amplitude of PF EPSP or the membrane properties of Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432093 TI - Dorsal raphe neurons: synchronous discharge with the theta rhythm of the hippocampus in the freely behaving rat. AB - 1. Single-unit activity of 30 dorsal raphe (DR) neurons was recorded along with the cortical and hippocampal electroencephalogram and neck muscle electromyogram in freely behaving rats during sleep-waking states. 2. On the basis of firing rates, DR cells were divided into slow-firing (S-cells), fast firing (F-cells), and very fast firing (FF-cells) units. The S-cells (8 units) fired at rates of < 10 Hz, the F-cells (11 units) at 10-40 Hz, and the FF-cells (11 units) at 55-70 Hz. 3. The activity of 17 of 30 DR units was correlated with the theta rhythm of the hippocampus. They included both slow and rapidly firing DR neurons. These cells typically fired irregularly (single spikes or short-duration bursts of activity) during non-theta states of quiet waking and slow-wave sleep. With the change of behavioral state to awake-moving or rapid eye movement sleep, the activity of these units switched to a regular bursting pattern synchronous with the hippocampal theta rhythm. Seven of these 17 units were classified as theta rhythmic cells on the basis of the tight phase-locking of their discharge to the hippocampal theta rhythm. The remaining 10 units were classified as theta modulated cells on the basis of a smaller but significant coherence between unit discharge and the theta rhythm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432094 TI - Sexual dimorphism in the vertebrate nervous system. PMID- 1432095 TI - Alteration of long-lasting structural and functional effects of kainic acid in the hippocampus by brief treatment with phenobarbital. AB - Kainic acid, an analog of the excitatory amino acid L-glutamate, induces acute hyperexcitability and permanent structural alterations in the hippocampal formation of the adult rat. Administration of kainic acid is followed by acute seizures in hippocampal pathways, neuronal loss in CA3 and the hilus of the dentate gyrus, and reorganization of the synaptic connections of the mossy fiber pathway. Rats with these hippocampal structural alterations have increased susceptibility to kindling. To evaluate the role of the acute seizures and associated hippocampal structural alterations in the development of this long lasting susceptibility, rats that received intraventricular kainic acid were cotreated with phenobarbital (60 mg/kg, s.c., once daily). Treatment with this dose for 5 d after administration of kainic acid suppressed acute seizure activity, protected against excitotoxic damage in the dentate gyrus, reduced mossy fiber sprouting, and completely abolished the increased susceptibility to kindling associated with kainic acid. Brief treatment with phenobarbital modified the pattern of damage and synaptic reorganization in the dentate gyrus in response to seizure-induced injury, and altered the long-lasting functional effects associated with hippocampal damage. As phenobarbital treatment did not protect against neuronal damage in CA3 or other regions of the hippocampus, the circuitry of the dentate gyrus was implicated as a locus of cellular alterations that influenced the development of kindling. These observations are evidence that pharmacological intervention can prevent the development of epilepsy in association with acquired structural lesions, and suggest that pharmacological modification of cellular responses to injury can favorably alter long-term functional effects of CNS damage. PMID- 1432096 TI - Temporal and harmonic combination-sensitive neurons in the zebra finch's HVc. AB - Song learning shapes the response properties of auditory neurons in the song system to become highly selective for the individual bird's own ("autogenous") song. The auditory representation of autogenous song is achieved in part by neurons that exhibit facilitated responses to combinations of components of song. To understand the circuits that underlie these complex properties, the combination sensitivity of single units in the hyperstriatum ventrale, pars caudale (HVc) of urethane-anesthetized zebra finches was studied. Some neurons exhibited nonlinear temporal summation, spectral summation, or both. The majority of these neurons exhibited low spontaneous rates and phasic responses. Most combination-sensitive neurons required highly accurate copies of sounds derived from the autogenous song and responded weakly to tone bursts, combinations of simple stimuli, or conspecific songs. Temporal combination-sensitive (TCS) neurons required either two or more segments of a single syllable, or two or more syllables of the autogenous song, to elicit a facilitated, excitatory response. TCS neurons integrated auditory input over periods ranging from 80 to 350 msec, although this represents a lower limit. Harmonic combination-sensitive (HCS) neurons required combinations of two harmonics with particular frequency and temporal characteristics that were similar to autogenous song syllables. Both TCS and HCS neurons responded much more weakly when the dynamical spectral features of the autogenous song or syllables were modified than when the dynamical amplitude (waveform) features of the songs were modified. These results suggest that understanding the temporal dynamics of auditory responses in HVc may provide insight into neuronal circuits modified by song learning. PMID- 1432097 TI - Posttetanic potentiation at the crayfish neuromuscular junction is dependent on both intracellular calcium and sodium ion accumulation. AB - The fluorescent indicator fura-2 was used to measure cytoplasmic calcium in presynaptic terminals in the crayfish Procambarus clarkii under conditions that raise intracellular sodium to examine whether sodium can elevate intracellular calcium concentration ([Ca2+]i) or prolong its efflux and thus influence the magnitude and duration of posttetanic potentiation (PTP). Sodium was elevated in presynaptic terminals at rest by either (1) injection of sodium into the excitatory axon, (2) application of veratridine to open sodium channels, or (3) addition of ouabain to block Na/K exchange, with [Ca2+]i increasing by either 430, 400, or 180 nM, respectively. Intracellular calcium concentration increased only when external calcium was present, indicating that calcium influx occurred through Na/Ca exchange. Additionally, ouabain enhanced excitatory junctional potentials (EJPs) eightfold. Elevation of sodium using a high-frequency stimulation in zero-calcium Ringer's did not elevate [Ca2+]i during the train or immediately afterward when calcium-containing Ringer's was re-introduced. This indicates that a physiological sodium load does not release calcium from internal stores or reverse Na/Ca exchange to levels where [Ca2+]i accumulation is detectable. We examined the ability of sodium to interfere with calcium efflux from presynaptic terminals by loading boutons with both sodium and calcium or calcium alone using high-potassium depolarization. Elevation of internal sodium slowed calcium efflux from the terminal (12.3 min) compared to calcium removal without a sodium load (4.0 min). When sodium loading was increased during a tetanus by application of ouabain, the time constants for decay of EJP potentiation, 17.3 min, and for [Ca2+]i, 35 min, were longer than control values, 4.4 min and 5.8 min, respectively. In addition, using lithium to inhibit the efflux of calcium by Na/Ca exchange following a PTP-inducing train also lengthened the decay of [Ca2+]i to 15.7 min. Intracellular sodium accumulation in presynaptic terminals slows the efflux of calcium through Na/Ca exchange, and may therefore augment and prolong PTP. PMID- 1432098 TI - Cell-specific expression of high levels of human S100 beta in transgenic mouse brain is dependent on gene dosage. AB - The beta-subunit of S100 protein (S100 beta) is highly conserved in the mammalian brain. The gene coding for human S100 beta has been mapped to chromosome 21. In order to study the consequences of overexpression of the S100 beta gene, transgenic mice were generated by microinjection of a 17.3 kilobase human genomic fragment containing the three exons and the transcription control elements of the human S100 beta gene. Mice from four transgenic lines carried approximately 10 100 transgene copies. Northern blotting demonstrated a tissue-specific and gene dose-dependent expression of human S100 beta mRNA in mouse brain. Increased expression of S100 beta mRNA was correlated with an increased production of S100 beta protein. Examination of brain sections by in situ hybridization and immunocytochemistry indicated that S100 beta was localized globally to astrocytes, as well as to discrete neurons in the mesencephalic and motor trigeminal, facial, and lemniscus nuclei in both normal and transgenic mice. In peripheral tissues, human S100 beta was expressed at 10-50-fold lower levels than in brain. The strict gene dosage dependence and cell specificity of transgene expression suggest the presence of a locus control region (LCR) in the human S100 beta gene. The mice tolerated 10-100-fold higher than normal levels of S100 beta gene expression in brain without any gross physical or behavioral abnormalities. The high-level expression and cell specificity of the S100 beta promoter/LCR suggest that it may provide a valuable tool to direct the expression of other transgenic products to specific cell types in the CNS. PMID- 1432099 TI - Increases in extracellular dopamine in the nucleus accumbens by cocaine are inversely related to basal levels: effects of acute and repeated administration. AB - Repeated administration of cocaine enhances several of the behavioral and neurochemical responses to subsequent cocaine injections, an effect that has been attributed, in part, to decreased somatodendritic autoreceptor sensitivity of mesocorticolimbic dopamine (DA) neurons. Such changes in autoregulation may not only modify the direct effects of cocaine on extracellular DA levels but also result in tonically increased basal DA release in the terminal areas of the mesocorticolimbic DA system. The present study was therefore designed to investigate the effects of repeated cocaine administration on basal extracellular DA concentrations in the nucleus accumbens (NAC) using in vivo microdialysis procedures in halothane-anesthetized rats. We subsequently examined the relationship between basal DA levels and the increase in extracellular DA produced by an acute injection of cocaine, and determined whether this relationship was altered by prior, repeated exposure to cocaine. Rats received one daily intraperitoneal injection of cocaine (30 mg/kg) or its vehicle (saline) for 10 consecutive days. On days 1, 3, or 7 after termination of the repeated cocaine treatment, extracellular DA levels in the NAC were determined under basal conditions and following a single intraperitoneal cocaine challenge injection (10 mg/kg) in separate groups of rats. Repeated cocaine administration produced a substantial increase in basal DA release in the NAC that was most prominent on day 1 post-cocaine (mean +/- SEM: 10.7 +/- 2.55 nM vs 3.55 +/- 0.56 nM) but was no longer apparent on day 7 post-cocaine. Higher extracellular DA levels were also observed after cocaine challenge in rats that received repeated cocaine treatments. Similar to the increase in basal release, this effect was most pronounced on day 1 post-cocaine (23.6 +/- 4.36 nM vs 12.61 +/- 1.76 nM) but did not persist through day 7 post-cocaine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432100 TI - Simulated motion enhances neuronal selectivity for a sound localization cue in background noise. AB - In nature, sound sources move and signals are accompanied by background noise. Noting that motion helps the perception of visual stimuli, we tested whether motion similarly facilitates the detection of acoustic targets, at the neuronal level. Auditory neurons in the central nucleus of the barn owl's inferior colliculus (ICc), due to their selectivity for interaural phase difference (delta phi), are sharply tuned to the azimuth of sound sources and are arrayed to form a topographic map of delta phi. While recording from single ICc neurons, we presented tones that simulated either moving or stationary sound sources with and without background noise. We found that the tuning of cells in the ICc for delta phi was sharper for stimuli that simulated motion than for those that simulated stationary targets. The neurons signaled the presence of a tone obscured by noise better if the tone moved than if the tone remained stationary. The resistance to noise observed with moving stimuli could not be reproduced with the temporal modulation of the stimulus amplitude, suggesting that a change of position over time was required. PMID- 1432101 TI - Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. AB - Cell culture studies with dissociated primary cultures from embryonic rat brain revealed that brain-derived neurotrophic factor (BDNF) promotes the developmental differentiation of both basal forebrain cholinergic and mesencephalic dopaminergic neurons. These studies suggested that, in the adult brain, BDNF may be able to protect cholinergic and dopaminergic neurons from degenerative changes induced by axotomy, similar to the known protective action of NGF in cholinergic neurons. Testing this hypothesis, we found that intraventricular administration of recombinant human BDNF (rhBDNF) to adult rats with transections of the fimbria significantly reduces axotomy-induced degenerative changes of the cholinergic cells in the basal forebrain. No such effect was seen on the dopaminergic neurons of the ventral mesencephalon after transection of their axons ascending in the medial forebrain bundle. Injected in equal amounts, rhBDNF and recombinant human NGF had quantitatively different effects on the cholinergic neurons. BDNF sustained only part of the population of cholinergic neurons affected by the lesion, whereas the entire population was protected by NGF treatment. PMID- 1432102 TI - Disruption of classical eyelid conditioning after cerebellar lesions: damage to a memory trace system or a simple performance deficit? AB - Over the past 10 years, a number of laboratories have reported that classically conditioned skeletal muscle responses, such as conditioned nictitating membrane/eyelid responses, are critically dependent on activity in the cerebellum. For example, unilateral lesions of the cerebellar interpositus nucleus have been shown to prevent acquisition and abolish retention of the conditioned eyelid response on the side ipsilateral to the lesions without affecting conditioned responding (CR) on the contralateral side. Also, recording studies involving the interpositus nucleus have consistently revealed patterns of neuronal discharge that predict execution of the CR. The lesion and recording studies have generally been cited as evidence that plasticity in the cerebellum is critically involved in the learning and memory of classically conditioned responses. This interpretation was recently challenged by Welsh and Harvey (1989a), who claimed that cerebellar lesions simply produced a performance deficit and speculated that the role of the cerebellum was not in learning and memory processes associated with the CR but only in performance of the eye blink response. Presented here are three experiments that provide additional strong evidence for a critical role of the cerebellum in the learning and memory of the Pavlovian CR. These experiments include (1) demonstrations of complete and permanent CR abolition after appropriate interpositus lesions, (2) a failure to find systematic or persisting decrements in the unconditioned response amplitude (i.e., the eye blink reflex) after appropriate interpositus lesion, and (3) observations of differential effects on the CR and unconditioned response after lesions were placed in populations of motoneurons responsible for executing the eye blink response. These data are discussed in the context of performance versus learning issues; evidence presented here rules out the possibility that interpositus lesion abolition of the eye blink CR is simply due to lesion effects on performance. PMID- 1432103 TI - Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity. AB - Excessive activation of NMDA receptors is thought to mediate the calcium dependent neurotoxicity associated with hypoxic-ischemic brain injury, trauma, epilepsy, and several neurodegenerative diseases. For this reason, various NMDA antagonists have been investigated for their therapeutic potential in these diseases, but heretofore none have proven to be both effective and safe. In the present study, memantine, an adamantane derivative similar to the antiviral drug amantadine, is shown to block the channels activated by NMDA receptor stimulation. From whole-cell and single-channel recording experiments, the mechanism of action of memantine is deduced to be open-channel block, similar to MK-801; however, unlike MK-801, memantine is well tolerated clinically. Compared to MK-801, memantine's safety may be related to its faster kinetics of action with rapid blocking and unblocking rates at low micromolar concentrations. Furthermore, at these levels memantine is an uncompetitive antagonist and should theoretically allow near-normal physiological NMDA activity throughout the brain even in the face of pathologically high focal concentrations of glutamate. These pharmacological properties confer upon memantine a therapeutic advantage against NMDA receptor-mediated neurotoxicity with few side effects compared with other organic NMDA open-channel blockers. Moreover, memantine is increasingly effective against escalating levels of glutamate, such as those observed during a stroke. Low micromolar concentrations of memantine, levels known to be tolerated by patients receiving the drug for the treatment of Parkinson's disease, prevent NMDA receptor-mediated neurotoxicity in cultures of rat cortical and retinal ganglion cell neurons; memantine also appears to be both safe and effective in a rat stroke model. These results suggest that memantine has considerable therapeutic potential for the myriad of clinical entities associated with NMDA receptor-mediated neurotoxicity. PMID- 1432104 TI - Promoter organization and activity of human monoamine oxidase (MAO) A and B genes. AB - Monoamine oxidase A and B (MAO A and B) play important roles in the metabolism of biogenic and dietary amines and are encoded by two genes derived from a common ancestral gene. The promoter regions for human MAO A and B genes have been characterized using a series of 5' flanking sequences linked to a human growth hormone reporter gene. When these constructs were transfected into NIH3T3, SHSY 5Y, and COS7 cells, the maximal promoter activity for MAO A was found in a 0.14 kilobase (kb) PvuII/DraII fragment (A0.14) and in a 0.15 kb PstI/NaeI fragment (B0.15) for MAO B. Both fragments are GC-rich, contain potential Sp1 binding sites, and are in the region where the MAO A and B 5' flanking sequences share the highest identity (approximately 60%). However, the organization of the transcription elements is distinctly different between these two promoters. Fragment A0.14 consists of three Sp1 elements, all in reversed orientations, and lacks a TATA box. Two of the Sp1 sites are located within the downstream 90 base pair (bp) direct repeat, and the third is located at the 3' end of the upstream 90 bp direct repeat. Fragment B0.15 contains an Sp1-CACCC-Sp1-TATA structure; deletion of any of these elements reduced promoter activity. Additional Sp1 sites, CACCC elements, CCAAT boxes, and direct repeats (four 30 bp direct repeats in MAO A and two 29 bp direct repeats in MAO B) are found in farther-upstream sequences of both genes (1.27 kb for MAO A and mostly in 0.2 kb for MAO B). Inclusion of these sequences decreased promoter activity. The different promoter organization of MAO A and B genes provides the basis for their different tissue- and cell-specific expression. PMID- 1432105 TI - Hormonal regulation of motor unit size and synaptic strength during synapse elimination in the rat levator ani muscle. AB - Previous anatomical studies suggest that androgen regulates synapse elimination in the androgen-sensitive levator ani(LA) muscle of the rat. Androgen treatment beginning on postnatal day 7 (P7) prevents some of the normal loss of multiaxonal innervation in this muscle. The present study used physiological techniques to measure the number and size of LA motor units during the synapse elimination period in muscles from normals, and castrates treated with either testosterone propionate or oil. The number of increments in LA twitch tension as nerve stimulation intensity increased, a measure of the number of motor units, was the same at the end (P28) of synapse elimination as near the beginning (P7) of this process. This result indicates that motoneuronal cell death does not contribute to synapse elimination in the LA. Moreover, androgen during this period did not influence the number of LA motor units. In contrast, between P7 and P28, there was a dramatic decline in the size of LA motor units, as indicated by a decrease in the percentage of twitch or tetanus tension of individual motor units relative to the maximal twitch or tetanus tension of the whole muscle. In addition, androgen treatment of castrated males during this period prevented some of the normal decline in the size of LA motor units. Estimates of the number of inputs per LA muscle fiber derived from the number of LA motor units and their average size indicate that androgen maintains polyneuronal innervation in the LA muscle. This finding supports previous anatomical studies suggesting that androgen can prevent synapse elimination in this muscle. The strength of LA synapses was also examined by measuring the tetanus: twitch ratio of individual motor units and by measuring the safety margin of LA synapses. Both measurements indicated that the average strength of LA synapses increases during synapse elimination. Moreover, androgen appeared to spare synapses from elimination without increasing their strength, since androgen-treated muscles generally had larger motor units but the same mean tetanus:twitch ratio and safety margins as untreated LA muscles except at P28, when synapses in androgen-treated LA muscles had appreciably lower safety margins than normal. These results suggest that androgen regulates synapse elimination through a mechanism(s) independent of synaptic strength. PMID- 1432106 TI - Fos-defined activity in rat brainstem following centripetal acceleration. AB - To identify rat brainstem nuclei involved in the initial, short-term response to a change in gravito-inertial force, adult Long-Evans rats were rotated in the horizontal plane for 90 min in complete darkness after they were eccentrically positioned off the axis of rotation (off-axis) causing a centripetal acceleration of 2 g. Neural activation was defined by the brainstem distribution of the c-fos primary response gene protein, Fos, using immunohistochemistry. The Fos labeling in off-axis animals was compared with that of control animals who were rotated on the axis of rotation (on-axis) with no centripetal acceleration, or who were restrained but not rotated. In the off-axis animals there was a significant labeling of neurons: in the inferior, medial, and y-group subnuclei of the vestibular complex; in subnuclei of the inferior olive, especially the dorsomedial cell column; in midbrain nuclei, including the interstitial nucleus of Cajal, nucleus of Darkschewitsch, Edinger-Westphal nucleus, and dorsolateral periaqueductal gray; in autonomic centers including the solitary nucleus, area postrema, and locus coeruleus; and in reticular nuclei including the lateral reticular nucleus and the lateral parabrachial nucleus. Also, there was greater Fos expression in the dorsomedial cell column, the principal inferior olive subnuclei, inferior vestibular nucleus, the dorsolateral central gray, and the locus coeruleus in animals who had their heads restrained compared to animals whose heads were not restrained. As one control, the vestibular neuroepithelium was destroyed by injecting sodium arsanilate into the middle ear, bilaterally. This resulted in a complete lack of Fos labeling in the vestibular nuclei and the inferior olive, and a significant reduction in labeling in other nuclei in the off-axis condition, indicating that these nuclei have a significant labyrinth sensitive component to their Fos labeling. The data indicate that several novel brainstem regions, including the dorsomedial cell column of the inferior olive and the periaqueductal gray, as well as more traditional brainstem nuclei including vestibular and oculomotor related nuclei, respond to otolith activation during a sustained centripetal acceleration. PMID- 1432107 TI - Muscarinic potentiation of IK in hippocampal neurons: electrophysiological characterization of the signal transduction pathway. AB - Central cholinergic (muscarinic) systems play an important role in learning and memory. In mammalian central neurons, muscarinic stimulation depresses several voltage-activated K+ currents and modulates synaptic transmission. Using whole cell voltage-clamp recordings in hippocampal CA1 neurons of rat brain slices, we report that activation of muscarinic receptors potentiates a voltage-activated, sustained K+ current (IK-type). This potentiation of IK is mediated by activation of protein kinase C and involves a G-protein-linked, intracellular Ca(2+) dependent process. This underlying second messenger pathway may prove to be important in the mediation of other previously reported muscarinic neuronal actions. PMID- 1432108 TI - Spatiotemporal sensitivity following lesions of area 18 in the cat. AB - The contribution of cat area 18 to spatiotemporal sensitivity and to motion processing was assessed in cats with unilateral ibotenic acid lesions placed in physiologically identified portions of area 18. The lesions were centered in the representation of the lower right visual field, about 10 degrees from the vertical meridian. In one of the animals, the lesion invaded a small portion of area 19. We measured detectability of various spatiotemporal stimuli placed within the lesioned and intact portions of the visual field, while monitoring eye position with a scleral search coil. We found a loss of sensitivity to gratings of low and intermediate spatial frequency, within the ablated portion of the visual field. The sensitivity loss was 0.6-1.0 log units at low and intermediate spatial frequencies, and decreased at higher frequencies with the resolution limits remaining intact. The loss extended over a range of temporal frequencies for both drifting gratings and grating modulated in counterphase. We also found that within the lesioned hemifield, the cats were unable to discriminate between rightward and leftward motion even at the highest contrasts. These results demonstrate that area 18 plays an important role in detecting drifting low- and intermediate-spatial-frequency targets and is likely to represent a critical stage in the cortical processing of motion signals. PMID- 1432109 TI - Inhibitory influence of the dorsal nucleus of the lateral lemniscus on binaural responses in the rat's inferior colliculus. AB - The contribution of the dorsal nucleus of the lateral lemniscus (DNLL) to binaural processing was examined by recording single-unit activity in the rat's inferior colliculus before, during, and after a reversible block of the excitatory activity in DNLL by local injection of kynurenic acid. Recordings were made from the central nucleus of the inferior colliculus with glass micropipettes filled with 3 M sodium acetate. Kynurenic acid (2 mM in Locke's solution) was injected into the DNLL through one side of a double-barreled glass pipette. The other side of the pipette was filled with Locke's solution for making control injections and recording neural activity. Pressure injection of 0.7-2.0 microliter of kynurenic acid resulted in the complete cessation of tone-evoked responses in DNLL for periods of 45 min to 1 hr. Tone bursts were delivered separately to the two ears through headphones fitted to the external auditory meatus. Binaural responses in the inferior colliculus were determined by comparing the effects of monaural and binaural stimulation. Attention was focused on neurons that were excited by contralateral stimulation and inhibited by ipsilateral stimulation. Interaural intensity difference (IID) functions were generated by holding contralateral sound pressure constant at 10 dB above threshold while increasing ipsilateral sound pressure level. Prior to kynurenic acid injection, ipsilateral stimulation caused a pronounced suppression of contralaterally evoked single-unit activity. Unilateral injection of kynurenic acid into DNLL reduced the strength of binaural suppression in the contralateral inferior colliculus. In every cell tested, the IID curve in inferior colliculus was shifted following contralateral DNLL injection. The IID curve returned to normal after recovery of neural activity in DNLL. In contrast, no effect was seen in the inferior colliculus ipsilateral to the kynurenic acid injection. The injection of Locke's solution into DNLL had no effect on IID curves in the inferior colliculus. These data suggest that the DNLL plays a role in binaural processing through an inhibitory influence on responses in the contralateral inferior colliculus. PMID- 1432110 TI - A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. AB - The mitogenic actions of epidermal growth factor (EGF) were examined in low density, dissociated cultures of embryonic day 14 mouse striatal primordia, under serum-free defined conditions. EGF induced the proliferation of single progenitor cells that began to divide between 5 and 7 d in vitro, and after 13 d in vitro had formed a cluster of undifferentiated cells that expressed nestin, an intermediate filament present in neuroepithelial stem cells. In the continued presence of EGF, cells migrated from the proliferating core and differentiated into neurons and astrocytes. The actions of EGF were mimicked by the homolog transforming growth factor alpha (TGF alpha), but not by NGF, basic fibroblast growth factor, platelet-derived growth factor, or TGF beta. In EGF-generated cultures, cells with neuronal morphology contained immunoreactivity for GABA, substance P, and methionine-enkephalin, three neurotransmitters of the adult striatum. Amplification of embryonic day 14 striatal mRNA by using reverse transcription/PCR revealed mRNAs for EGF, TGF alpha, and the EGF receptor. These findings suggest that EGF and/or TGF alpha may act on a multipotent progenitor cell in the striatum to generate both neurons and astrocytes. PMID- 1432111 TI - Clinical semiology of common cervicobrachial neuralgia. Data from 50 hospital cases. AB - Common cervicobrachial neuralgia is less frequent than sciatica and its aetiological profile is more varied: men and women are equally affected, triggering factors or previous history are less often found and patients with anxiety or depression are relatively numerous. Clinically, signs of C7 lesion are present in half the patients. Acroparesthesias are frequent and may be the initial signs. Nocturnal pain is present in 50% of the cases. Signs of neurological deficit are rare, except for abolition of a reflex. The association of cervicobrachial neuralgia with tendinitis of the upper limb or algodystrophy of the shoulder is too frequent to be fortuitous. Left to itself, the syndrome usually lasts several months and sometimes one year. Recurrences are rare. The most frequent sequela is a painful neck. PMID- 1432112 TI - Cervicobrachial neuralgia: diagnostic problems in neurology. AB - A population of 205 patients hospitalized for evaluation of cervicobrachial pain was retrospectively studied. Four aetiological groups were individualized: common cervicobrachial neuralgia (CBN) due to nucleus pulposus herniation or spondylarthrosis (119 cases); inflammatory radicular lesion (39 cases); CBN reflecting lesions of the cervicobrachial plexus or the spine (23 cases) and pain of undetermined origin (22 cases). The semiological characteristics of these four groups are discussed. PMID- 1432113 TI - Neurophysiological explorations in cervicobrachial neuralgia. AB - The various electrophysiological techniques which can be used in cervicobrachial neuralgia and their respective advantages and limitations are described. Beside the conventional electromyography and electrostimulation techniques, the indications for radicular motor and somesthetic evoked potentials are discussed. PMID- 1432114 TI - Plain radiography in the evaluation of cervicobrachial neuralgia. AB - Standard radiography is indispensable to the initial evaluation of cervicobrachial neuralgia. Its main purpose is not to detect a nucleus pulposus herniation or a spondylarthrosis responsible for the neuralgia, but to exclude a possible malignancy. In some cases standard radiography points out to a less frequent cause, such as constitutional stenosis of intervertebral foramina not necessarily associated with a narrow vertebral canal. PMID- 1432115 TI - CT, myelography and CT-myelography in the evaluation of common cervicobrachial neuralgia. AB - The CT technique used to explore intervertebral discs and foramina is described, as are the CT signs of nucleus pulposus (NP) herniation and cervical degenerative lesions. CT with intravenous contrast injection is the most efficient and easiest method to diagnose a radicular compression of discal or degenerative origin. The advent of high-resolution contrast CT will probably make obsolete the use of contrast media. CT measures the width of the vertebral canal, but it does not evaluate the repercussions on the spinal cord of compression caused by NP herniation or osteophytosis: only CT-myelography or, better, MRI can make this evaluation. Conventional CT scans are sometimes inadequate when exploration is hampered by superimposition of the shoulders (C6-C7 and more often C7-T1), when the scanner is of poor quality or when it is misused. Myelography and CT myelography can then be utilized to resolve the problem posed by C7 or C8 cervicobrachial neuralgia (CBN). CT makes it possible to exclude most of the causes of non-discal CBN in the extradural spaces (e.g. bone tumour, neurinoma, vertebral vascular malformation, paravertebral expansive process, apical lung tumour). The search for an intradural cause (extra- or intramedullary tumour) rests on myelography, CT-myelography and MRI. PMID- 1432116 TI - MRI and cervicobrachial neuralgia. AB - Recent improvements in magnetic resonance imaging techniques have altered our choices in the exploration of cervicobrachial neuralgia (CBN). The use of high field machines, new acquisition sequences and paramagnetic contrast media has increased the sensitivity and specificity of the MRI method in the detection of degenerative lesions responsible for CBN. These new techniques are essentially based on gradient-echo sequences can be acquired in two or three dimensions, and each of them has its own advantages and drawbacks, but their performance is sufficient for MRI to be now considered a reliable and non-traumatic exploratory method for CBN. Performed after standard radiography, MRI tends to be the first choice examination in the preoperative evaluation of cervical radiculopathies and myelopathies. PMID- 1432117 TI - Medical treatment of common cervicobrachial neuralgia. PMID- 1432118 TI - Treatment of cervicobrachial neuralgia in orthopaedic medicine. AB - Orthopaedic and physiotherapeutic treatments must necessarily complete the medicinal treatment of common cervicobrachial neuralgia. Rest in a posture that suppresses or attenuates the disc-nerve root conflict is mandatory. The use of physical agents (ultrasounds, short waves), rehabilitation, local injections, vertebral tractions and manipulations depends on the results of clinical examination. Every anatomico-clinical lesion detected has indications that guide the therapeutic approach. Close supervision of these treatments is indispensable to modify their rhythm and intensity or to stop them. PMID- 1432119 TI - Results of surgical treatment for cervicobrachial neuralgia. A retrospective study of 122 patients with long-term follow-up. AB - Surgical nerve root decompression is rarely needed in the treatment of cervicobrachial neuralgia. In patients with prolonged and resistant pain or neurological deficits, or when signs of associated spinal cord suffering have been found, various surgical procedures can be used, but is most cases the disco arthro-radicular conflict can be solved by the anterior approach with or without bone graft. This review of long-term results in a series of 122 patients operated upon and re-examined more than 3 years later shows that the radicular symptoms were relieved in 95% of the cases. Evaluation of anatomical results did not reveal any instability or aggravation of discarthrosis at the site of surgery. However, in 30% of the cases disc degeneration was increased in the over- and underlying levels but without recurrence of clinical symptoms; 4% of the patients in this series were reoperated upon for this aggravated or de novo disc disease. The authors underline the importance of a thorough radioanatomical examination not only to decide whether or not a "soft hernia" or an arthrotic hypertrophy should be operated, but also to evaluate the extent of the decompressive operation to be performed. PMID- 1432120 TI - Automated percutaneous nucleotomy in the treatment of cervicobrachial neuralgia due to disc herniation. AB - Forty-five patients suffering from cervicobrachial neuralgia resistant to medical treatment were treated by automated percutaneous nucleotomy according to the technique used by Onik et al. in the lumbar segment of the spine. Good results were obtained with this technique in 85% of the patients. This figure is similar to that reported for nucleorthesis without the risk of calcification mentioned in the literature. PMID- 1432121 TI - The radiologist and common cervicobrachial neuralgia. AB - The neuroradiological methods used for the diagnosis of common cervicobrachial neuralgia are not the same in all medical centres and hospitals, one of the main reasons for this lack of unanimity being differences in organization and availability of equipment. However, the modern diagnostic approach should include magnetic resonance as first examination. MRI is the most informative and the least hazardous of all exploratory methods, and it detects or excludes a much greater number of causes than any other radiological technique. False-negative results, as well as late, incomplete or wrong diagnosis are therefore reduced to the minimum. False-positive results can be avoided by a good knowledge of the physiological incidence of uncodiscarthrosis with age. PMID- 1432122 TI - M. Stephen Mahaley, Jr., M.D., Ph.D., 1932-1992. PMID- 1432123 TI - Linear accelerator radiosurgery for arteriovenous malformations. AB - Between May, 1988, and August, 1991, 80 patients with arteriovenous malformations (AVM's) were treated radiosurgically at the University of Florida. A mean dose of 1650 cGy was directed to the periphery of the lesion, which almost always corresponded to the 80% isodose line. The mean lesion diameter was 23 mm. Seventy six patients were treated with one isocenter. Angiography, performed at 1 year after radiosurgery in 41 of the 48 eligible patients, revealed an overall complete thrombosis rate of 39%. The 1-year thrombosis rate was highest in those patients with relatively small AVM's. Angiography was performed at 2 years posttreatment in 21 of the 25 eligible patients, demonstrating an overall complete thrombosis rate of 81%. This incidence did not correlate with lesion size: that is, large lesions (up to 35 mm in diameter) seemed just as likely to thrombose. Two patients (2.5%) experienced hemorrhage at some time after radiosurgical treatment, and both recovered. Two patients (2.5%) have sustained mild, but permanent, radiation-induced neurological complications. PMID- 1432124 TI - Superselective intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage. AB - This report describes the successful treatment of cerebral vasospasm after subarachnoid hemorrhage with superselective intra-arterial infusion of papaverine hydrochloride. Thirty-seven vascular territories in 10 patients with symptomatic vasospasm were treated according to the following protocol. Percutaneous transluminal angioplasty was performed in two steps. First, a silicone balloon was used for dilation of the internal carotid artery and the proximal portions of the middle cerebral artery. A silicone leak balloon or Tracker-18 catheter was then introduced into or just proximal to the site of vasospasm not accessible to the angioplasty balloon catheter for superselective infusion of 0.2% papaverine. Thirty-four of 37 vascular territories were successfully dilated, and eight of 10 patients showed improvement in neurological function after the procedure. There were no serious side effects due to infusion of papaverine. It is essential to infuse the papaverine just proximal to the spastic vessels in order to deliver sufficient concentration of drug, and infusion should be carried out as early as possible before the artery loses its ability to return to a normal luminal size. Superselective intraarterial infusion of papaverine is an alternative method of treatment for symptomatic vasospasm. PMID- 1432125 TI - Treatment of cerebral vasospasm with intra-arterial papaverine. AB - Cerebral vasospasm continues to be the leading treatable cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage. In this preliminary anecdotal series of 12 patients who were candidates for balloon angioplasty, vasospasm was treated instead with intra-arterial papaverine. Eight patients had marked angiographic reversal of the arterial narrowing following papaverine infusion, four of whom showed dramatic reversal of profound neurological deficits. Two patients deteriorated clinically 5 days after the initially successful papaverine infusions. In both, repeat angiography demonstrated severe recurrent vasospasm, which was partially reversed with a second intra-arterial papaverine treatment. Two patients developed focal neurological deficits during papaverine infusion, which resolved spontaneously over several hours after cessation of the intra-arterial infusion. Arterial narrowing in the posterior circulation and middle cerebral artery distribution appeared to be more responsive to papaverine infusion than was spasm in the anterior cerebral arteries. The infusion of 300 mg of papaverine over 1 hour seemed to be an adequate and safe dose to effect these angiographic and clinical improvements. PMID- 1432126 TI - The treatment of associated intracranial aneurysms and arteriovenous malformations. AB - Cerebral arterial aneurysm associated with arteriovenous malformation (AVM) has been described with a variable incidence, averaging 10% of AVM cases. The present series includes 39 patients with this association, derived from a total of 400 patients with AVM's evaluated and treated since 1970. The aneurysms are classified into four major groups, each carrying particular therapeutic implications. Optimum treatment of these lesions is based in part on a knowledge of the hemodynamic alterations associated with the AVM's. In most of these cases, the symptomatic lesion was treated first; occasionally, when feasible, both lesions were treated during the same operation. All patients had some form of treatment, either surgical or endovascular, directed to at least one of the two types of lesions. All symptomatic lesions were treated and all ruptured aneurysms were obliterated. There were no deaths in this series. PMID- 1432127 TI - Transpedicular screw-rod fixation of the lumbar spine: operative technique and outcome in 104 cases. AB - A total of 104 patients underwent transpedicular spinal instrumentation using the Cotrel-Dubousset (71 cases) or the Texas Scottish Rite Hospital (33) screw-rod system. Surgery was performed for lumbar vertebral column instability secondary to fractures (28 cases), spondylolisthesis (29), tumors (four), vertebral osteomyelitis (two), or postoperative causes (41). Pseudoarthrodesis due to failure of a prior fusion was present in 37 cases. The 55 men and 49 women (mean age 47 years, range 18 to 87 years) all presented with severe back pain. Signs or symptoms of neural compression were noted in 96 patients. Surgery consisted of neural decompression, internal fixation, and autogenous iliac bone grafting. Spondylolistheses were fused in situ, without reduction; otherwise, major spinal deformities were corrected. A total of 516 pedicle screws were placed. The mean extent of fusion was 2.7 motion segments (range one to six motion segments). A 96% fusion rate was obtained with a mean follow-up period of 20 months. There were no operative deaths. Major complications included one spinal epidural hematoma, three isolated nerve root deficits (two transient, one permanent), and three wound infections (two deep, one superficial). Instrument failure eventually developed in 18 patients; nine were asymptomatic with a solid fusion and did not require further treatment and the other nine were symptomatic or had a pseudoarthrosis and required operative revision. Pedicle screw-rod fixation offers biomechanical advantages compared to other forms of internal fixation for the lumbar spine. It enables short-segment fixation with preservation of lumbar lordosis and adjacent normal motion segments. This technique provides a highly successful method to obtain arthrodesis, even with prior pseudoarthrosis. PMID- 1432128 TI - Syrinx shunt to posterior fossa cisterns (syringocisternostomy) for bypassing obstructions of upper cervical theca. AB - Syrinx shunts to the spinal subarachnoid space are likely to fail if the cerebrospinal fluid pathways rostral to the syrinx are blocked. To bypass obstructions at or below the level of the foramen magnum, a technique was developed for shunting the syrinx to the posterior fossa cisterns, termed "syringocisternostomy." Syrinxes were shunted to the cisterna magna in two patients with spinal arachnoiditis and to the cerebellopontine angle cistern in four patients with Chiari I malformations. There was symptomatic improvement and collapse of the syrinx in each case, with no complications or recurrences over a follow-up interval of 14 to 27 months (average 20.3 months). The surgical technique and results of treatment are described. PMID- 1432129 TI - Shunt implantation: reducing the incidence of shunt infection. AB - Shunt infection remains the foremost problem of shunt implantation after mechanical malfunctions. Diversionary cerebrospinal fluid shunt implantation has a high complication rate, with 5% to 15% of such shunts becoming infected. Of these infections, 70% are diagnosed within 1 month after surgery and more than 90% within 6 months. Shunt infection in the vast majority of cases is therefore a complication of shunt surgery. The authors review their experience with shunt implantation during two time periods. From January, 1978, to December, 1982, 302 children with hydrocephalus underwent 606 operations. Among these children, 47 (15.56%) developed a proven shunt infection, with an incidence of infection per procedure of 7.75%. As a result of this study, a new protocol for shunt procedures involving modifications in the immediate pre-, intra-, and postoperative management of children undergoing shunt implantation was initiated. With this new protocol, 600 children underwent a total of 1197 procedures between January, 1983, and December, 1990. The incidence of shunt infection decreased dramatically, with two infections (0.33%) in 600 patients and a per-procedure rate of 0.17%. The overall annual risk of a shunt infection in the pediatric neurosurgical unit is currently 1.04%. PMID- 1432130 TI - Outcome following hindbrain decompression of symptomatic Chiari malformations in children previously treated with myelomeningocele closure and shunts. AB - Between 1975 and 1989, 25 children treated with myelomeningocele closure and shunting for hydrocephalus at the Children's Hospital of Pittsburgh developed progressive lower brain-stem dysfunction from their Chiari malformation. Retrospective univariate and multivariate analyses of these cases were undertaken to assess the relationship between preoperative clinical factors and postoperative outcome. Since earlier reports have suggested that neonates with symptomatic Chiari malformations show a less favorable response than older children to craniocervical decompression, particular attention was directed at examining the effect of age on preoperative symptoms and postoperative outcome. Patients were subdivided by age into two groups, namely: 13 patients who became symptomatic before 2 months of age (neonatal group) and 12 older infants and children who developed initial symptoms between 6 months and 10 years of age. Once symptoms developed, patients in both groups deteriorated progressively until brain-stem decompression was performed. The mode of presentation and the rate and extent of neurological deterioration differed substantially in the two groups. Whereas the neonates typically showed rapid neurological deterioration and often manifested profound brain-stem dysfunction within a period of several days, the older patients experienced a more insidious symptom progression and rarely demonstrated the severe degree of impairment seen in the neonates. All patients underwent suboccipital craniectomy, cervical laminectomy, and dural decompression. A shunt from the fourth ventricle and/or syrinx to the subarachnoid space was placed in those with significant syringomyelia. Following surgery, 17 patients had complete or nearly complete resolution of all signs of brain-stem compression, three had mild to moderate residual deficits, and five showed no improvement. Outcome correlated closely with the preoperative neurological status. In particular, the presence of bilateral vocal cord paralysis was associated with a poor response to surgery (p < 0.001 on both univariate and multivariate analyses). Of the six patients (all neonates) who progressed to complete bilateral vocal cord paralysis before surgery, only one improved. In contrast, all patients with less profound but nonetheless severe deficits recovered function postoperatively. Although the neonates as a group had a poorer outcome than did the older patients (p = 0.02 on univariate analysis), this in large part reflected their more severe preoperative impairments; neonates who still had some preservation of vocal cord function before surgery subsequently did as well as the older patients. Accordingly, age did not prove to be an independent prognostic factor on multivariate analysis. Taken together, these results indicate that, in most patients with symptomatic Chiari II malformations (including neonates), neurological deficits are potentially reversible if hindbrain decompression is performed expeditiously. PMID- 1432131 TI - Cerebral hemicorticectomy for epilepsy. AB - Hemicorticectomy resulted in total or near-total control of seizures in 10 of 11 children with chronic epilepsy. During a median follow-up period of 5.5 years, there have been no deaths or delayed complications. The surgical outcome after hemicorticectomy compares favorably with that of more extensive surgical procedures, yet is associated with significantly less risk. The technique for hemicorticectomy is described and illustrated. PMID- 1432132 TI - Surgical management of symptomatic pineal cysts. AB - The authors present a series of six patients with large symptomatic benign pineal cysts and review the 27 patients previously reported in the literature. Patients with symptomatic pineal cysts most often present with one of three syndromes: 1) paroxysmal headache with gaze paresis; 2) chronic headache, gaze paresis, papilledema, and hydrocephalus; or 3) pineal apoplexy with acute hydrocephalus. Surgical intervention with radical cyst removal is the treatment of choice for all symptomatic pineal cysts. Complete cyst removal is desirable; however, radical subtotal resection is appropriate if the cyst cannot be easily separated from the quadrigeminal plate. Ventricular shunting should be reserved for patients with persistent hydrocephalus after cyst resection. PMID- 1432133 TI - Extracranial complications of severe head injury. AB - In order to define the role of intracranial and extracranial complications in determining outcome from severe head injury, 734 patients from the Traumatic Coma Data Bank were analyzed. Nine classes of intracranial and 13 classes of extracranial complications occurring within the first 14 days after admission were analyzed, while controlling for age, admission Glasgow Coma Scale motor score, early hypoxia or hypotension, and severe extracranial trauma. Outcome for survivors was based on the last recorded Glasgow Outcome Scale score, obtained a median of 521 days after injury. Intracranial complications did not significantly alter outcome for the study group. Of the extracranial complications, pulmonary, cardiovascular, coagulation, and electrolyte disorders occurred most frequently at 2 to 4 days. Infections developed later, peaking at 5 to 11 days. Gastrointestinal, renal, and hepatic complications followed no specific time course. Electrolyte abnormalities were the most frequent occurrence (59% of patients) but did not alter outcome. Pulmonary infections (41%), shock (29%, systemic blood pressure < or = 90 mm Hg for 30 minutes or more), coagulopathy (19%), and septicemia (10%) were significant independent predictors of an unfavorable outcome. Backward-elimination, stepwise logistic regression modeling indicated that the estimated reduction of unfavorable outcome was 2.9% for the elimination of pneumonia, 3.1% for coagulation disturbances, 1.5% for septicemia, and 9.3% for shock. These data suggest that extracranial complications are highly influential in determining the outcome from severe head injury and that significant improvements in outcome in a sizeable proportion of patients could be accomplished by improving the ability to prevent or reverse pneumonia, hypotension, coagulopathy, and sepsis. PMID- 1432134 TI - Unruptured aneurysms and postoperative volume expansion. AB - After a ruptured aneurysm has been clipped in patients with multiple aneurysms, the question often arises whether to use volume expansion and/or hypertensive treatment to prevent delayed cerebral ischemia (vasospasm). There is understandable concern regarding the possible rupture of unprotected aneurysms under additional hemodynamic stress. In a series of 199 patients with aneurysmal subarachnoid hemorrhage who underwent early surgery, 31 were left with one or more unprotected aneurysms postoperatively. All patients were treated with prophylactic volume expansion based on a previously reported protocol. Mean central venous pressure during treatment was 10.3 cm H2O and mean arterial blood pressure 141/76 mm Hg; volume expansion was continued for 7 to 10 days. Eight patients developed symptoms of delayed cerebral ischemia and required additional volume expansion and induced hypertension. After institution of hypertension, four of these patients experienced a reversal of their symptoms, while four others developed cerebral infarcts. One patient died from massive cerebral infarction following vasospasm refractory to all measures. No patient suffered rupture of an unprotected aneurysm during hypervolemic treatment. It is concluded that the benefit of prophylactic hypervolemic hypertension in postoperative aneurysm patients warrants its use even in patients with unprotected aneurysms. PMID- 1432135 TI - Effects of intermittent reperfusion during temporal focal ischemia. AB - There is controversy regarding the role of intermittent reperfusion employed as a cerebroprotective measure when temporary arterial occlusion is necessary during repair of difficult aneurysms. The intraluminal suture middle cerebral artery (MCA) occlusion technique was used in 23 Wistar rats under barbiturate anesthesia to induce 60, 90, or 120 minutes of uninterrupted MCA occlusion. The total infarcted areas obtained were compared to those occurring in 27 animals subjected to identical cumulative ischemic periods but with 5 minutes of reperfusion after every 10-minute ischemic period. The mean total infarcted areas in the groups with 60-minute (1.8 +/- 0.89 sq mm), 90-minute (1.08 +/- 1.02 sq mm), and 120 minute (8.72 +/- 5.89 sq mm) intermittent reperfusion were significantly smaller than those occurring in the 60-minute (12.02 +/- 3.10 sq mm), 90-minute (11.54 +/ 2.68 sq mm), or 120-minute (30.43 +/- 6.51 sq mm) control groups, respectively (p < 0.05). Furthermore, there was no difference in the occurrence of blood-brain barrier breakdown, intraparenchymal hemorrhage, hemispheric edema, or seizures between control and intermittent reperfusion groups. The results support the hypothesis that intermittent reperfusion is beneficial if vessel occlusion is required during aneurysm repair. PMID- 1432136 TI - Regional metabolism in experimental brain tumors in cats: relationship with acid/base, water, and electrolyte homeostasis. AB - Experimental brain tumors were produced in cats by xenotransplantation of the rat glioma clone F98 into the white matter of the left hemisphere. One to 4 weeks after implantation, local adenosine triphosphate (ATP), glucose, lactate, and tissue pH were measured via imaging techniques in cryostat sections passing through the center of the tumor and correlated with changes in water and electrolyte content. The tumors exhibited a heterogeneous metabolic pattern, with a tendency for ATP to decrease and lactate to increase during tumor development. Tissue pH was above 7.5 in tumors with high ATP content but it sharply declined at low ATP levels. In peritumoral edema, ATP also decreased and lactate increased but, in contrast to tumor tissue, pH became more alkaline. Metabolic changes were associated with edema formation, as evidenced by the rise in water and sodium content. There was a distinct difference between tumor tissue and peritumoral edema: in tumor tissue, pH declined with increasing water content, whereas in peritumoral edema it increased. These observations are interpreted as follows: 1) in tumor tissue, "lactacidosis" and ATP depletion are attributed to disturbances in blood flow, resulting in metabolic failure and the intracellular "cytotoxic" accumulation of water; 2) in peritumoral edema, "lactalkalosis" is the result of an efflux of (alkaline) lactate salts from the tumor into the expanded extracellular compartment, and the decrease in ATP is the volumetric effect of extracellular "vasogenic" edema fluid and not the result of cellular energy failure. These findings are of importance for the interpretation of volume selective magnetic resonance spectroscopy and may contribute to the establishment of spectroscopic criteria for the evaluation of therapeutical interventions. PMID- 1432137 TI - Variability of the territories of the major cerebral arteries. AB - Recent morphological and functional studies on the circle of Willis suggest that the areas of supply of the six major cerebral arteries show a considerable variation in distribution, in contrast to the relatively consistent pattern generally accepted; therefore, the cortical and intracerebral distribution of the territories of these arteries was investigated in 25 unfixed human brains obtained at routine autopsy. The six major cerebral arteries were simultaneously injected under the same pressure with different-colored Araldite F mixtures under standardized conditions to obtain the most realistic territorial distribution. The cortical boundaries were examined and recorded in relation to the cerebral gyri and sulci, and the territories of the anterior, middle, and posterior cerebral arteries were analyzed and compared. The intracerebral distribution of these territories was investigated after the injected brains were cut in parallel slices. The variability of the territories of these arteries was much larger than generally described in the literature. Twenty-six variations in the territory of the anterior cerebral artery, 17 variations in the area of the middle cerebral artery, and 22 variations in the area of the posterior cerebral artery were found in the cortex of 50 hemispheres. Intracerebrally, the anterior, middle, and posterior cerebral arteries contributed in varying degrees to the blood supply of the lobar white matter, the internal capsule, the caudate nucleus, and the lentiform nucleus. The large variation in the area in which the cortical and intracerebral boundaries between these territories was located was demonstrated by illustrating the minimum and maximum extent of each. The results are compared with prior findings, and their implications for both experimental model studies and clinical practice are discussed. PMID- 1432138 TI - Angioplasty for basilar artery atherosclerosis. Case report. AB - A case is presented of severe atherosclerosis of the basilar artery, successfully treated with percutaneous transluminal balloon angioplasty. Crescendo daily transient ischemic attacks consisted of alternating hemiplegia and were refractory to medical management, including anticoagulation therapy. The clinical course, endovascular treatment, and results are described. Prior published experiences with this condition are reviewed. PMID- 1432139 TI - Acute cauda equina syndrome from a ruptured aneurysm in the sacral canal. Case report. AB - The case is presented of a young woman with acute cauda equina syndrome from a ruptured aneurysm in the sacral canal. The lesion was associated with pathological enlargement of the lateral sacral arteries bilaterally, which presumably occurred to provide cross-pelvic collateral flow in response to the diversion of the right internal iliac artery for renal transplantation. The patient presented with signs and symptoms of spontaneous spinal epidural hemorrhage. The radiographic features of this lesion are described. In addition to angiography and partial embolization of the vascular supply, contrast-enhanced high-resolution computerized tomography was essential in the diagnosis and treatment of this unique aneurysm. PMID- 1432140 TI - Bilateral morning glory syndrome associated with sphenoid encephalocele. Case report. AB - Morning glory syndrome is a congenital anomaly of the optic disc in which the disc is enlarged and excavated, with white glial tissue in the center. A case is presented of morning glory syndrome associated with sphenoid encephalocele, median cleft lip, and agenesis of the corpus callosum. A 22-day-old boy was referred to the Wakayama Medical College Hospital for management of dyspnea due to a soft-tissue mass in the oral cavity. Magnetic resonance imaging revealed a mass extending through a bone defect in the sphenoid region and into the oral cavity. Surgical repair was attempted through a bifrontal craniotomy. A bone defect was identified in the sphenoid plate, through which the arachnoid membrane was connected to the oral cavity. Both optic nerves were elongated and adhered to the encephalocele. The wall of the meningocele was compressed digitally through the oral cavity and sutured to the dura mater of the bone defect. The operative findings suggest that a basal encephalocele protruding from a bone defect in the sphenoid plate may disturb the normal development of the optic nerve. PMID- 1432142 TI - A two-step supraorbital approach to lesions of the orbital apex. Technical note. AB - A two-step supraorbital approach to lesions of the orbital apex is described. This technique is easy and allows a satisfactory exposure of the region. In addition, the reconstruction resulting from the procedure is anatomically perfect. The authors report the operative results obtained in 20 patients and compare this two-step supraorbital procedure with similar surgical techniques described previously. PMID- 1432141 TI - Transaqueductal migration of a neurocysticercus cyst. Case report. AB - The clearly documented transaqueductal migration of a solitary intraventricular neurocysticercus cyst is described. The cyst was fortuitously demonstrated on magnetic resonance imaging during migration through the aqueduct. The radiological appearance and clinical significance of this condition are discussed. PMID- 1432143 TI - Development of neurosurgery at the University of Michigan. AB - The University of Michigan Medical School was founded in 1847, 30 years after the university itself. The first hospital in Ann Arbor was a 20-bed unit converted from a private house, that admitted only charity patients. The second University Hospital was built in 1925. The Section of Neurosurgery was founded by Dr. Max Peet, who was followed by Drs. Kahn and Schneider as section heads. PMID- 1432144 TI - The death of Henry II of France. AB - On June 30, 1559, King Henry II of France (1519-1559), against the advice of his court ministers, participated in a fateful joust. The wooden lance of his younger opponent pierced the King's headgear, shattered into fragments, and penetrated his right orbit and temple. The King survived for 11 days following the mortal wound and was treated by two of the most distinguished physicians of the Renaissance: Ambroise Pare (1510-1590), the master surgeon, and Andreas Vesalius (1514-1564), the great anatomist. The unfortunate event, the nature of the injury, and the medical consultation between these eminent physicians should all be of interest to neurosurgeons. The historical consequences of this event are briefly reviewed. PMID- 1432145 TI - Contamination of jugular bulb venous oxygen measurements. PMID- 1432146 TI - Breaks in Mayfield head holder. PMID- 1432147 TI - Maintenance of Mayfield head rest. PMID- 1432148 TI - Risks of laser discolysis. PMID- 1432149 TI - Dual-isotope brain SPECT imaging with technetium-99m and iodine-123: clinical validation using xenon-133 SPECT. AB - Our phantom studies indicate that the energy resolution (9.7% FWHM) of a new three-headed single-photon tomograph (PRISM-3000) separates the distribution of 99mTc from 123I for 10% asymmetric or 15% or 10% centered 99mTc windows when combined with a 10% asymmetric 123I window. This technique is now applied to the simultaneous measurement of resting rCBF and changes induced by vasodilation (1 g acetazolamide) in 10 subjects with cerebrovascular disease. Resting and vasodilated 133Xe SPECT images were obtained first. Within 48 hr, 99mTc HMPAO was given at rest, acetazolamide injected, and after 20 min either [123I] IMP or [123I] HIPDM was administered. Subjects were scanned for 99mTc and 123I simultaneously using 10% asymmetric windows. Regression analyses demonstrated a linear relationship between 133Xe SPECT and dual-isotope SPECT measurements of lesion-to-cerebellum ratios in baseline (r = 0.92), vasodilated (r = 0.86) and rest-minus-vasodilated data (r = 0.85). Technetium-99m and 123I images obtained through dual-isotope imaging are by definition in perfect anatomic registration. PMID- 1432150 TI - The role of sestamibi scintigraphy in the radioisotopic assessment of myocardial viability. AB - The relationship between sestamibi uptake as a marker of myocardial viability and postrevascularization function recovery is still to be defined. We studied 14 patients (13 males, 1 female, mean age 55 +/- 7 yr, range 35 to 64 yr) with sestamibi scintigraphy, quantitative coronary angiography and two-dimensional echocardiography. Sestamibi uptake was quantified from planar images and expressed as percent of maximal activity in each projection using a 13-segment model. All defects were subgrouped on the basis of the severity of reduction in sestamibi uptake; the limit of viability was set at 2.5 s.d. below the normal uptake (55%). Echocardiography was analyzed using a score index ranging from 1 (normokinesis) to 4 (dyskinesis) and a corresponding regional model. Before revascularization, 42 segments were grouped as normal (coronary stenosis < 50% and normal function, Group 1); of the remaining 140 segments related to > 50% coronary stenosis, 67 had normal wall motion (Group 2) and 73 showed regional dyssynergies (Group 3). Sestamibi percent activity was high in Group 1 and significantly reduced in both Group 2 and 3 segments. Pre- and postrevascularization echocardiography was compared in all patients. Sestamibi sensitivity and specificity in the detection of postrevascularization recovery of function was 83% and 71%, respectively; positive predictive accuracy was 79%. The presence of a severe defect identified most of those segments with wall motion abnormalities that did not recover following coronary revascularization; however, sestamibi overestimated rest perfusion defects in 25% of territories supplied by stenotic coronary arteries that had normal wall motion at rest. Sestamibi appears to be primarily a perfusion agent that can provide limited information regarding viability. PMID- 1432151 TI - PET-fluorodeoxyglucose of cranial and spinal neuromas. AB - Five patients with eighth nerve, one with ninth nerve and one with cervical neuromas were studied with PET and [18F] fluorodeoxyglucose (FDG). Four of the patients had had surgery prior to the PET study, and six patients had subsequent surgery. All tumors were well-visualized on the PET images. Only one patient with bilateral acoustic neuroma exhibited tumor recurrence or growth after the PET study; these two lesions showed the highest FDG uptakes in the PET studies (tumor to-cerebellum ratio of 0.93-0.98). All other tumors were relatively hypometabolic (tumor-cerebellum ratios of 0.43-0.65) and showed no tumor growth or recurrence during follow-up periods ranging from 5 to 8 yr. These results suggest that PET FDG may be of value in the evaluation of cranial and spinal schwannomas. PMID- 1432153 TI - Go with the flow--but how far? PMID- 1432152 TI - Can dynamic krypton-81m imaging separate regional ventilation and volume? AB - This study explores the assumption that 81mKr static images represent regional ventilation. Dynamic acquisition of 81mKr ventilation images permits creation of time-activity curves and the possible separation of the confounding influences of ventilation and volume. By using a two-compartment gas mixing lung phantom, the results demonstrate that both total and tidal 81mKr are closely related to regional ventilation. In 61 children and 15 adult volunteers, there was good agreement between fractional ventilation assessed by total and tidal 81mKr. The dynamic steady-state ventilation image can be analyzed to separate tidally exchanged and resident 81mKr. This may allow regional ventilation to be distinguished from regional volume. PMID- 1432154 TI - Brain SPECT in neonates following extracorporeal membrane oxygenation: evaluation of technique and preliminary results. AB - Extracorporeal membrane oxygenation (ECMO) is a life-saving procedure in neonates with refractory respiratory failure that has been used at our institution since 1985. In an attempt to study its clinical value, regional cerebral blood flow (rCBF) alterations were measured using SPECT and 99mTc-HMPAO in 13 newborns following ECMO. Eight infants were studied after ECMO with reanastomosis of the right common carotid artery (RCCA), two with the permanent ligation of the RCCA, and three after veno-venous ECMO. Brain SPECT was technically satisfactory in all newborns using a triple-head SPECT system. Altered rCBF was found in 7 of 13 infants. In five newborns, there was a decrease in rCBF within the ipsilateral hemisphere, and in one infant, contralateral hemisphere was involved. In one infant, there was bilateral hemispheric involvement. The infant underwent cardiopulmonary resuscitation prior to ECMO and exhibited clinical features of hypoxicischemic encephalopathy at the time of SPECT. Only 2 of 13 newborns demonstrated morphologic changes on neuroimaging modalities such as cranial ultrasonography, computed tomography and magnetic resonance imaging. Our study demonstrates that: (1) functional brain imaging is feasible in neonates after ECMO; (2) SPECT has potential for demonstrating rCBF deficits not detectable by neuroanatomic imaging modalities; and (3) SPECT has potential clinical value in long-term follow-up of neurodevelopmental outcome after ECMO. PMID- 1432155 TI - Human pharmacokinetics and radiopharmacological studies of the myocardial perfusion agent: technetium (2-carbomethoxy-2-isocyano-propane)6+. AB - The myocardial perfusion agent technetium (2-carbomethoxy-2-isocyano-propane)6+ (99mTc-CPI) is unique from other cationic technetium isonitrile complexes in that it exhibits moderate washout from the heart and rapid hepatobiliary clearance in animal models and human volunteers. Dynamic imaging and HPLC analysis were performed in humans and guinea pigs to outline the pharmacological basis of its pharmacokinetics. Enzymatic hydrolysis of the terminal ester groups in blood was found to occur at a moderate rate producing new species that have been shown not to accumulate in heart tissue. However, after extraction by the heart, liver or kidneys, the 99mTc-CPI complex undergoes metabolism at a much slower rate than observed in the blood. Differences in hydrolysis rate and products obtained indicate separate mechanisms of hydrolysis occurring in blood and other organs. It is proposed that the heart washout occurring after hydrolysis produces a neutral compound which is no longer retained by the negative cytosolic and mitochondrial membrane potentials in myocardial tissue. PMID- 1432156 TI - Specific and nonspecific immunoassays to detect HAMA after administration of indium-111-labeled OV-TL 3 F(ab')2 monoclonal antibody to patients with ovarian cancer. AB - The development of human anti-mouse antibodies (HAMA) may cause problems in radioimmunotargeting studies, but may also improve survival of patients. To identify the presence of HAMA in blood samples from patients intravenously injected with 1 mg of 111In-labeled OV-TL3-F(ab')2, we developed three specific OV-TL 3-based HAMA assays and tested these along with two commercially available nonspecific HAMA assays (Sorin and Immunomedics). The specific assays were positive for HAMA with 10 postinjection serum samples from 7 patients. Eight of the 10 samples were also HAMA positive with one or both nonspecific HAMA assays. Conflicting results were observed with half the number of samples. The two nonspecific assays also reacted positively with another 11 serum samples from 5 patients including their preinjection samples. Despite some contradictory results, the nonspecific HAMA assays identify both pre-existent and Mab-induced HAMA, whereas the specific OV-TL3-based HAMA assays identify specific immune responses occurring after the OV-TL 3 injection. PMID- 1432157 TI - Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123 IBZM. AB - We studied the uptake, distribution, metabolism and washout of the dopamine D2 receptor ligand [123I]IBZM in healthy subjects (n = 12) with dynamic brain SPECT. The highest radioactivity level was detected in the striatum. Operationally defined striatal "specific" uptake peaked at 69 min postinjection of radioligand and showed a gradual decline of 15% per hour thereafter. "Specific" uptake at maximal counts represented 53% of the total striatal radioactivity. Two subjects received haloperidol (20 micrograms/kg i.v.) 80 min postinjection of radioligand. Haloperidol caused a 2.6-fold increase in the rate of washout of specific striatal activity in comparison to that in the 10 control subjects and was consistent with drug-induced displacement of radioligand from the dopamine D2 receptor. Two classes of metabolites were detected in plasma and urine: a polar fraction, not extracted by ethyl acetate, and a nonpolar, extractable fraction consisting of parent compound and two compounds having shorter retention times on reversed-phase HPLC. Greater than half the plasma parent was metabolized within 10-15 min after administration. The volume of distribution, estimated from the peak arterial plasma concentration at 50-75 sec, was 7.7-10.2 l; the free (nonprotein bound) fraction of [123I]IBZM after in vitro incubation with blood or plasma was 4.4% +/- 0.4%. These results suggest that [123I]IBZM exhibits uptake in brain regions with high D2 receptor density and shows a relatively stable washout during which drugs affecting dopaminergic transmission may be administered. PMID- 1432158 TI - Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. AB - While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D [3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment. PMID- 1432159 TI - Metabolic design of combination therapy: use of enhanced fluorodeoxyglucose uptake caused by chemotherapy. AB - In order to quantify effects of an experimental chemotherapy, MCF7 cells were studied with 14C-fluorodeoxyglucose (FDG) and high-performance liquid chromatography (HPLC). Uptake measurements were performed 1 and 4 hr after the end of a therapy with hexadecylphosphocholine (HPC). A dose- and time-dependent increase of the FDG uptake after therapy was observed, with a maximum at 1 hr after therapy. These data were used to develop a new metabolic design of combination treatment. Several time-dose combinations of HPC and deoxyglucose (DOG) were analyzed for their effects on growth inhibition. The combinations using DOG in the period of pronounced enhancement of FDG uptake (1 hr after HPC treatment) were found to be the most effective with an improvement of up to 520% in growth inhibition. This metabolic design of combination treatment may also be applied in vivo, and PET can be used to optimize the time and dose schedule of the modified treatment protocol. PMID- 1432160 TI - Comparison of technetium-99m-glucarate and thallium-201 for the identification of acute myocardial infarction in rats. AB - The scintigraphic identification of acute severe ischemic myocardial injury requires a marker that localizes rapidly and specifically in zones of damaged myocardium. Technetium-99m-glucarate, a six-carbon dicarboxylic acid, which behaves in vivo somewhat like fructose, was recently described as a marker of severe acute ischemic injury with necrosis. This study was performed to determine the interval between the onset of myocardial ischemia and initial uptake and the duration of a positive scan in experimental animals. Serial injections and images were recorded over 10 days following ligation of the left anterior descending coronary artery of the rat. The distribution of 99mTc-glucarate was compared to that of regional myocardial perfusion monitored with 201TI. The findings on radionuclide imaging were compared to histologic changes in the myocardium. Sequential pinhole images of both radionuclides were collected at 3 hr, 24 hr, 72 hr and 7-10 days following ligation. Ten rats had normal 201TI distributions, no uptake of glucarate and no evidence of infarction by TTC staining at autopsy. Twenty-one rats had either 201TI lesions or evidence of infarction at autopsy. In 17 of these rats, significant acute 99mTc-glucarate uptake was noted, decreasing at 24 hr, and was not seen at 72 hr or 7-10 days. The extent of perfusion abnormality was greatest at 3 hr in most animals; the lesion decreased in four (33%), increased in one (8%) and remained stable in the remainder. These data suggest that 99mTc-glucarate may be a useful marker of acute myocardial injury. PMID- 1432161 TI - Imaging of cardiac transplantation rejection in primates using two new antimyosin agents. AB - Indium-111-labeled monoclonal antimyosin Fab has been used to image myocardial infarction, myocarditis and cardiac transplant rejection with localization in myocytes that have suffered irreversible loss of cell membrane integrity. Technical factors potentially limiting clinical usefulness of 111In antimyosin include dosimetry (72 hr half-life of 111In), slow blood clearance of antibody proteins delaying optimal imaging to 24 to 48 hr postinjection and nontarget organ uptake. Therefore, two new antimyosin imaging agents experimentally shown to potentially improve dosimetry, shorten time from injection to imaging or decrease nonspecific cell binding were evaluated in a primate cardiac transplant model. The two agents evaluated were polylysine 111In-antimyosin (0.023 mg Fab modified with a 3.3 kd polymer of polylysine and labeled with 111In) and 99mTc antimyosin (0.5 mg Fab' antimyosin labeled using the RP-1 ligand technique). A total of eight baboons were studied: three with heterotopic (cervical) xenographs, three with orthotopic allographs and two control animals. Each animal was injected first with 12-23 mCi of 99mTc-RP-1 antimyosin and 5-16 hr after completion of imaging, was injected with 0.72-1.88 mCi of 111In-polylysine antimyosin (PIs) and reimaged 12-48 hr later. The imaging results were compared to the histology of the animals. Biexponential curves were fit to the blood sample data and rate constants were determined and expressed as T1/2 values. There were no significant differences between the two agents in either the early fast components or the late slow components. On planar imaging, there was blood pool activity at 10-12 hr postinjection of both agents, but by 16-24 hr postinjection, blood pool was negligible on the 111In-PIs scans. Both agents were concentrated in the rejected cardiac tissue. The slow blood-pool clearance combined with the 6 hr half-life of 99mTc-RP-1 AMA make this agent less promising for detection of diffuse myocardial uptake than 111In Fab modified with polylysine. PMID- 1432162 TI - Experimental and clinical analysis of the characteristics of a chimeric monoclonal antibody, MOv18, reactive with an ovarian cancer-associated antigen. AB - Monoclonal antibody (Mab) MOv18 preferentially reacts with gynecological carcinomas. We have analyzed the characteristics of murine MOv18 (m-MOv18) and chimeric MOv18 (c-MOv18). We found no differences in affinity and binding to IGROV1 cells between c-MOv18 as IgG and F(ab')2 fragments and m-MOv18. In nude mice bearing IGROV1 xenografts, maximum tumor uptake 6-15 hr after i.v. injection of radiolabeled m-MOv18 IgG, c-MOv18 IgG, c-MOv18 F(ab')2 and a control IgG, 2C7, was 10%, 11%, 3% and 4.5% of the injected dose/g (%ID/g), respectively. M- and c MOv18 IgG retained this level for several days, while c-MOv18 F(ab')2 and 2C7 cleared rapidly from the tumor. Uptake in normal tissues was low, with the exception of high uptake in kidneys for c-MOv18 F(ab')2. Tumor/blood ratios for c MOv18 F(ab')2 were sixfold higher than for IgG. Radiation absorbed doses to tumor tissue delivered by 10 microCi iodinated m-MOv18 IgG, c-MOv18 IgG and c-MOv18 F(ab')2 were 39 cGy, 49 cGy and 5 cGy, respectively. A cocktail of 125I-c-MOv18 IgG and 131I-c-MOv18 F(ab')2 injected i.v. into an ovarian cancer patient, localized specifically in the tumor. Ovarian cancer tissue samples obtained 2 days postinjection showed a mean uptake of 1.2 x 10(-3) and 2.7 x 10(-3) %ID/g for c-MOv18 IgG and c-MOv18 F(ab')2, respectively. Results from these in vitro and in vivo experiments indicate that c-MOv18 has promise as a Mab for clinical use. PMID- 1432163 TI - Pretargeted immunoscintigraphy: effect of hapten valency on murine tumor uptake. AB - A method of radioimmunoscintigraphy using bivalent "Janus" haptens with an apparent enhanced affinity ("avidity") for the antibody is described. Janus with 50 micrograms pretargeted Mab WC3A11 resulted in significantly higher murine tumor concentrations (approximately 7%/g) compared to monovalent haptens (approximately 1.4%/g, p < 0.001), and the same high tumor-to-background ratios (approximately 3/1). Janus was synthesized by coupling two molecules of BABE together with a 1,4 butanedithiol linker. Janus itself was rapidly excreted (T1/2b = 42 min) by the kidneys and did not concentrate in any other organs or tissues. Three-step pretargeted immunoscintigraphy (binder, chaser, tracer) with 111In- or 67Ga-Co(III) Janus produced excellent mouse tumor images in 3 hr with high tumor-to-background ratios. The use of short-lived tracers, such as 99mTc and 68Ga, with a T1/2p of hours to image antibodies that localize slowly over several days in vivo is accessible with this new technology. PMID- 1432164 TI - Abnormal intracerebral thallium localization in a bacterial brain abscess. AB - A 56-yr-old man with a prior history of renal cell carcinoma had moderately intense abnormal localization of 201Tl-chloride in a solitary brain lesion which was discovered to be a bacterial abscess. The organisms isolated by culture included Actinomycosis odontolyticus, Peptostreptococcus and Hemophilus aphrophilus. Because of the clinical presentation, MRI characteristics and thallium scintigraphic findings, the lesion had been felt to represent either a primary or a metastatic neoplasm. This case illustrates the need for caution in the interpretation of thallium brain scintigram. PMID- 1432166 TI - An autonomously functioning thyroid carcinoma associated with euthyroid Graves' disease. AB - A 39-yr-old man with an autonomously functioning thyroid carcinoma is presented. Only 17 similar cases have been reported in the literature. The patient had unilateral Graves' ophthalmopathy. He was euthyroid as reflected by normal TSH concentration, whereas the results of a T3 suppression test established the presence of autonomous thyroid function. A thyroid scan with (123)I revealed a hot nodule corresponding to the location of a papillary carcinoma and remained substantially unchanged after T3 administration. The hyperfunction of the carcinoma itself was clearly confirmed by the intense concentration of (131)I within the tumor on microautoradiograms. While a hot nodule on radioiodine scan is unlikely to be malignant, the possibility of carcinoma should not be overlooked. PMID- 1432165 TI - PET scanning of iodine-124-3F9 as an approach to tumor dosimetry during treatment planning for radioimmunotherapy in a child with neuroblastoma. AB - A patient with advanced neuroblastoma who had failed chemotherapy presented with a large abdominal mass and virtually total bone marrow replacement by tumor on repeated marrow biopsies. She was considered a candidate for a Phase I 131I-3F8 radioimmunotherapy trial, (MSKCC 89-141A). As a potential aid to treatment planning, a test dose of 124I-3F8 was injected and the patient was imaged over the 72 hr postinjection using two BGO based PET scanners of different designs. Time activity curves were obtained, and the cumulated activity concentration of radiolabeled 3F8 in tumor was determined. Based on MIRD, an estimated radiation absorbed dose for 131I-3F8 was 7.55 rad/mCi, in the most antibody avid lesions. Because of low uptake and unfavorable dosimetry in some bulky tumor sites, it was decided not to treat the patient with radiolabeled antibody. Positron emission tomography of 124I-labeled antibodies can be used to measure cumulated activity or residence time in tumor for more accurate estimates of radiation absorbed tumor dose from radioiodinated antibodies and can help guide management decisions in patients who are candidates for radioimmunotherapy. PMID- 1432167 TI - Indium-111-leukocyte and gallium-67 imaging in acute sarcoidosis: report of two patients. AB - Two young women with acute sarcoidosis underwent (111)In-labeled autologous leukocyte imaging because of persistent fevers. Images of one of the women demonstrated faint thoracic lymph node uptake of labeled cells, but no discrete focus suggestive of infection was seen. Images of the second woman were normal. Gallium-67 imaging, performed 48 hr after the leukocyte studies, revealed multiple areas of abnormal radiotracer accumulation corresponding to regions of active sarcoid in both women. These cases suggest that leukocyte imaging is not useful for assessing the extent of disease in patients with sarcoidosis. This technique may be valuable, however, in excluding superimposed infection in these individuals. PMID- 1432168 TI - Dual-isotope brain SPECT imaging with technetium-99m and iodine-123: validation by phantom studies. AB - Phantom studies were employed to determine whether the enhanced energy resolution (9.7% FWHM) of a new high-resolution, three-headed single-photon emission computed tomograph might permit the simultaneous acquisition of 99mTc and (123)I. Various window widths (15% and 10%) and positions (centered and asymmetric to the photopeak) were used to examine cross-contamination between these two isotopes. Brain phantom experiments using a 15% centered 99mTc window in conjunction with a 10% asymmetric (123)I window (upper half of the (123)I photopeak) demonstrated that approximately 95% of observed counts were derived from the isotope of interest. Shifting the (123)I window from asymmetric to centered resulted in a significant increase in contamination of the (123)I window. Shifting the 99mTc window from centered to asymmetric did not significantly alter image quality for 99mTc. Separate experiments employing vials with varying isotope concentrations demonstrated that quantitative recovery from mixed 99mTc and (123)I sources was equivalent to that from matched single-isotope sources (r2 > or = to 0.90). PMID- 1432169 TI - Ventilation perfusion lung scanning in the evaluation of right-to-left shunting. PMID- 1432170 TI - Prognostic value of captopril renal scintigraphy in renovascular hypertension. AB - This study evaluates the prognostic value of captopril renal scintigraphy in hypertensive patients undergoing renal artery revascularization. Preoperative studies of 51 patients were correlated with blood pressure results at 6- and 12 mo follow-up. Captopril-renal scintigraphy was carried out 1 hr after oral administration of 50 mg of captopril, using either 220 MBq of 99mTc-DTPA or 74 MBq of 99mTc-MAG3, followed by a baseline study in case of abnormal results. Evidence of amelioration or normalization in relation to captopril study was considered predictive of blood pressure control following treatment. Blood pressure response was favorable in 37 patients, but failed to show any improvement in 14. The scintigraphic test was positive in 33 patients (15 cured, 17 improved, 1 failed) and negative in 18 (3 cured, 2 improved, 13 failed). Sensitivity and specificity for renovascular hypertension was 86.5% and 93%, respectively. For blood pressure cure and improvement, the test had positive and negative predictive values of 97% and 72%, respectively. A positive preoperative captopril renal scintigraphic result is a strong predictor of hypertension curability by renal artery revascularization. PMID- 1432171 TI - Captopril renal scintigraphy--a way to distinguish functional from anatomic renal artery stenosis. PMID- 1432172 TI - The "well tempered" diuretic renogram: a standard method to examine the asymptomatic neonate with hydronephrosis or hydroureteronephrosis. A report from combined meetings of The Society for Fetal Urology and members of The Pediatric Nuclear Medicine Council--The Society of Nuclear Medicine. AB - Perinatal hydronephrosis (HN) and hydroureteronephrosis (HUN) are recognized more frequently as the routine use of prenatal ultrasonography increases. The decision making process for those instances of urinary tract dilatation that require surgical correction and those that do not is based in part on the findings of diuresis renography. The methodology for performing this test has differed among nuclear medicine practitioners and the surgical findings are occasionally discrepant from the diuretic renogram interpretation. Consequently, the Society of Fetal Urology (SFU) and the Pediatric Nuclear Medicine Council (PNMC) of the Society of Nuclear Medicine met to develop by consensus a more uniform methodology. A standard method has been agreed upon for the following facets of diuretic renography: patient preparation (hydration and bladder catheterization), diuresis renography technique (radiopharmaceutical used, patient position during examination, data acquisition parameters, diuretic pharmaceutical and dosage, time of injection and regions of interest to monitor diuretic effect), and data analysis (percent differential renal function, curve pattern analysis and methods of measuring diuretic response). Pooled diuresis renogram data are being collected for analysis for correlation with surgical results and clinical outcomes to determine the most appropriate information to be derived from the diuretic renogram in neonates with HN and HUN. PMID- 1432173 TI - Diffuse abdominal uptake of technetium-99m-methylene diphosphonate in a patient on continuous ambulatory dialysis during bone scintigraphy. AB - Extra-skeletal uptake of bone seeking radiopharmaceuticals has been documented by scintigraphy. We present a case of diffuse uptake of 99mTc-methylene diphosphonate (MDP) in the abdomen of a patient while undergoing continuous ambulatory peritoneal dialysis (CAPD) who had no symptoms or findings referable to the abdomen. We hypothesized that the 99mTc-MDP crossed the peritoneal membrane across a concentration gradient. An in-vitro simulation confirms that 99mTc-MDP will cross a semi-permeable membrane. Diffuse uptake of 99mTc-MDP may be a normal variant in patients on CAPD who have no signs or symptoms of peritonitis. PMID- 1432174 TI - Clarification of traditional bases for ethics. PMID- 1432175 TI - First-pass versus gated equilibrium radioangiography. PMID- 1432176 TI - Large bolus radionuclide esophageal transit may predict response to esophageal dilatation in achalasia. PMID- 1432177 TI - Technical considerations in the handling of a cadaver having received radioiodine prior to death. PMID- 1432178 TI - Acupuncture and radioactive pathways of hypodermically injected technetium-99m. PMID- 1432179 TI - Scientists report surprise findings of thyroid cancer following Chernobyl. PMID- 1432180 TI - Congress begins support of the National Biomedical Tracer Facility. PMID- 1432181 TI - Blues approve indications for PET. PMID- 1432182 TI - The SNM Manpower Survey report. PMID- 1432183 TI - Revising your manuscript. PMID- 1432184 TI - Feeling refreshed: helping RNs return to the work force. AB - In light of the nursing shortage, many hospitals are turning to refresher courses to meet staffing needs. To be successful, the course must be designed to meet the needs of both the participant and the hospital. Although the exact structure of the course will vary by institution, this article details steps taken at one hospital to help registered nurses return to nursing. PMID- 1432185 TI - A new clinical educator role: bridging the education-practice gap. AB - A new clinical educator role implemented at Georgetown University Hospital is described in this article. Nurses in this role assume dual responsibilities for nursing staff development and clinical supervision of baccalaureate nursing students. These clinical educators have joint appointments in the Department of Nursing and the School of Nursing. This role helps to bridge the education practice gap and encourages a more efficient use of nursing resources. PMID- 1432186 TI - Assertiveness training: does it make a difference? AB - The impact of assertiveness training on job-related functioning has not been evaluated. This study, conducted in a tertiary care psychiatric facility, assessed whether assertiveness training changed nurses' perceptions of assertiveness, attitudes toward power, functioning within the nursing team, and functioning within the multidisciplinary team. This article describes a four-part assertiveness training course that was found to significantly affect feelings of assertiveness. PMID- 1432187 TI - Teaching the nurse to teach with health information videos. AB - Using health information videos is a common way to teach hospitalized patients. This article describes a study of medical and surgical patients in an acute care hospital. In Phase I, patients' frequency of Patient Health Information Television use and their knowledge of programs and scheduling were evaluated. Phase 2 identified patients' learning after viewing selected programs. In Phase I, frequency of use, peak viewer time, and viewer encouragement strategies were revealed. In Phase II, the efficacy of televised patient education was documented. Results indicate that nursing staff development educators should teach nurses how to work with this educational medium. PMID- 1432188 TI - A hierarchical approach to unit-based nursing orientation. AB - Using a hierarchical approach to orientation is a means to address the needs of both the orientee and the institution. The Hierarchical Orientation Model, described in this article, focuses on the development of skills in patient assessment and management and on organization sensitivity and integration. The model is based on adult learning principles that include building on previous knowledge and self-paced learning. Although developed for a tertiary pediatric hospital, the Hierarchical Orientation Model can be applied to other settings. PMID- 1432189 TI - Opioid analgesics: nurses' knowledge of doses and psychological dependence. AB - Lack of education of health professionals, including nurses, is frequently cited as a major reason for undertreatment of pain. Very recent surveys have revealed an urgent need for basic and continuing nursing education to address this problem. For example, little time is spent on the topic of pain in many baccalaureate nursing programs, nursing textbooks lack correct information about opioid addiction, and most practicing nurses currently do not possess knowledge about opioid analgesics that would enable them to administer opioids effectively. The authors report on a survey of 1,781 practicing nurses' specific knowledge deficits regarding opioid analgesics and propose some solutions. PMID- 1432190 TI - Critical Care Blitz Weekend: fun for all. PMID- 1432191 TI - Innovative staff development approaches for NCLEX-RN success. AB - NCLEX-RN Licensure success is achievable when the institution provides administrative support, has a committed staff development department, and allocates necessary resources and support services. This program was designed and delivered in a cost-effective manner. The candidates attended the on-site review course and tutoring sessions before their assigned work time. The tutoring sessions offered by the staff development instructors were held during their regularly scheduled hours. The consultant's fee for the on-site review course was $200 per eligible candidate, for a total of $7,600. Specifically, employers and staff development departments must take a strong role not only in acclimating newly graduated and foreign-educated nurses to the professional environment, but also in helping to prepare them for the NCLEX-RN Licensure Examination. Thus, staff development educators can effectively ensure that their institutions will not lose valuable registered nurses. PMID- 1432192 TI - Inservice day benefits staff. PMID- 1432193 TI - Strategy implementation, evaluation and control. PMID- 1432194 TI - Effect of Orem's model on nurse attitudes and charting behavior. AB - This article describes a program evaluation that examines the effect of Orem's self-care nursing model on the attitudes of nurses and on charting behavior. Implementing Orem's model increased staff nurse satisfaction with nursing and enhanced nurses' perception of the value of patient teaching. PMID- 1432195 TI - Helping new graduates succeed at the NCLEX-RN experience: evaluation of an anxiety-reducing workshop. AB - A descriptive, longitudinal study was conducted to determine the effectiveness of a 2-day workshop designed to reduce the anxiety levels of new graduates participating in the NCLEX-RN examination. A hospital nurse administrator, in collaboration with nurse educators, provided a multimodal in-service program. "Test wiseness," or test-taking strategies, and exercises related to physical and emotional well-being, were included for three groups of new graduates. Using Zung's Self-rating Anxiety Scale to collect data, reduction in anxiety after the workshop and at the completion of the NCLEX-RN experience was identified. All participants in the program passed the NCLEX-RN examination. PMID- 1432196 TI - Characteristics of critical care nursing internship programs. AB - Development of programs to prepare new graduate nurses to work in critical care units has been a priority for nurse educators for many years. Despite the presence of many such internship programs, little data are available about the characteristics of such programs. Results of this study suggest that the development of internship programs designed to prepare new graduate nurses in critical care nursing continues to be a priority. The standards used by these programs are individualized and are often reflective of the unique needs of the institution. Costs of these programs are quite high. Recommendations for future directions based upon the results of the study are offered. PMID- 1432197 TI - Mouth-to-mask resuscitation in the hospital: perceived problems of staff and variations in technique. AB - Mouth-to-mask resuscitation is used by many hospitals to implement "Universal Infection Precautions" and is now mandatory for health care Basic Cardiac Life Support (BCLS) courses nationwide. In the past, mouth-to-mask resuscitation was not routinely performed in hospital settings, and was optional in health care BCLS courses. This study suggests needed changes in mouth-to-mask resuscitation training and use. These findings can be used by nurse educators who are frequently responsible for implementing and evaluating BCLS programs. PMID- 1432198 TI - Team building for the staff development department. AB - Development of effective teamwork is a deliberate process. The leader assumes a major role in this process. The payoff for team building begins with the increased professional growth of members that may ultimately result in improved overall organizational effectiveness. This article describes the major roles a leader plays in helping groups become teams. PMID- 1432199 TI - Planning a peer review program. AB - The purpose of this study was to provide a basis for the planning and subsequent implementation of a peer review program, concomitant to exploring the perceptions of registered nurses regarding initiating a peer review program in a small midwestern hospital. The study findings indicated that registered nurses liked the peer review process, perceived peer review as helping their professional growth, and indicated a strong desire for education and in-service. Based on the study results, planning and recommendations for further implementation are discussed. PMID- 1432200 TI - New instructor orientation: a formalized process. PMID- 1432201 TI - Needs assessment. PMID- 1432202 TI - AONE's perspective on healthcare reform. PMID- 1432203 TI - Nurse administrators in job transition: managing the exit. PMID- 1432204 TI - Legal and ethical issues in HIV testing, Part 1. AB - HIV antibody testing presents multiple and complex legal and ethical issues. Nurse executives must be knowledgeable about these issues and their potential impact on administrative practice. In this two-part series, the author presents legal and ethical issues related to testing. Part 1 focuses on the AIDS epidemic, the ELISA test, informed consent, confidentiality, and mandatory vs. voluntary testing. PMID- 1432205 TI - Contract management. Filling the void created by CNE vacancies. AB - Contract management can provide interim chief nurse executives (CNEs) during the search process for a permanent executive. Experienced and effective, interim nursing executives can communicate to all audiences, prepare the organization for the next permanent nursing executive, and their presence avoids problems that arise during a long recruitment period. Typically, interim nursing executives find that working through contract management is a rewarding and challenging experience. PMID- 1432206 TI - Developing home care standards you can count on ... and cost on! AB - Cost management is a six-step process that begins with identifying important activities of patient care, identifying desired outcomes of patient care, and the most predictable and efficient process to be used to ensure outcome accomplishment. The more caregivers and managers understand the cost-benefit connection between patient care and resource costs, the easier it will be for them to manage (rather than be a victim of) quality, productivity, and profitability. PMID- 1432207 TI - Nursing: asset or liability. PMID- 1432208 TI - Designing roles for assistive personnel in a rural hospital. AB - The role development of assistive personnel has become more important in rural hospitals because of the limited professional nursing supply. St. Mary's Hospital has fostered interdepartmental collaboration to reallocate duties to personnel who are best qualified to perform them. The dyad model, uniquely tailored to this hospital's needs, has resulted in the more efficient and effective use of personnel. PMID- 1432209 TI - Teleconferencing. Home health administrators and educators enhance graduate education. AB - In light of the current condition of university budgets, enhancing graduate education can be a challenge for nurse educators. One effective and inexpensive strategy is teleconferencing. This strategy allows graduate students to network with nurse leaders nationwide without the expense of travel. Teleconferencing could also be adapted in other areas to bring service and educational professionals together. PMID- 1432210 TI - Demystifying the intensive care unit. PMID- 1432211 TI - Operating room productivity. An evaluation format. AB - Operating room (OR) directors are frequently faced with the challenge of explaining or justifying OR productivity and the OR staffing budget. This justification may occur annually in conjunction with their budget submission or when consultants are employed to evaluate and improve OR productivity. Whatever the circumstance, a simple step-by-step format that helps physicians and administrators understand the impact of productivity on the nursing budget can be most useful. The authors present a format that was successfully used at a Boston teaching hospital. PMID- 1432212 TI - A strategy for growth in home care. The clinical nurse specialist. AB - One of the most challenging problems that faces today's home healthcare providers is how to deliver quality care within the constraints imposed by changing population, limited resources, and regulations. This problem is particularly apparent to those who provide rural healthcare. Use of the clinical nurse specialist can promote quality care while facilitating the development and expansion of home health services. PMID- 1432213 TI - HIV treatment costs staggering. PMID- 1432214 TI - Nursing research in the VA system. A consortium approach. AB - Five Veterans' Administration Medical Centers formed a consortium to promote nursing research. Consortium arrangements focusing on research are reviewed based on the literature, the consortium's experience, and a survey of 171 VA facilities. Consortiums are suggested for multisite facilities, such as city, state, proprietary, and religious hospital systems, to increase the quality and quantity of nursing research where institutional mechanisms for overcoming the difficulties of meeting and sharing information are already in place. PMID- 1432215 TI - Optimizing nursing information systems. AB - Financial, billing, and admission/discharge/transfer software applications have been available for years. Many administrators are purchasing systems to obtain automation to support nursing needs. However, administrators cannot rely on internal experience or software vendors to design their systems because not many have been operational long enough to have been sufficiently tested. In this article, the author provides a background of current functionality available, how clinical applications can interface for efficient documentation, and a strategy for developing the design of a new system. PMID- 1432216 TI - Employment and functional impairment affect caregivers. PMID- 1432217 TI - Discharge planning: collaboration between the community and the acute care hospital. PMID- 1432218 TI - Premium pay cuts agency costs. PMID- 1432219 TI - The nurse practitioner in tertiary care. PMID- 1432221 TI - The handwriting on the wall. Warning signs of impending job loss. AB - Can nurse executives read the handwriting on the wall when they or another nurse executive are facing a forced resignation or termination? What are the warning signs of an eroding job position, including the relationship between the chief nurse executive and the chief executive officer? How much time does a nurse executive typically have in the job once the warning signs begin to show? The authors discuss these questions and specific tactics and strategies suggested by warning signs. PMID- 1432220 TI - The nurse case manager: focus, selection, preparation, and measurement. PMID- 1432222 TI - A new look for quality in home care. AB - The management of quality is being transformed in healthcare. Continuous improvement is a cornerstone to this new look at quality. However, no continuous quality program will succeed without incorporating the values and wants of the consumer of care and the end point they want to reach. This article presents an overview of the values to consider and the way to define outcomes. PMID- 1432224 TI - 'Conspiracy' surrounds HIV exposure. PMID- 1432223 TI - Community-hospital partnerships. The Quick Response Team. AB - The Quick Response Team project was an intervention designed and implemented by the Capital Regional District Care Program in partnership with the Greater Victoria Hospital Society. The aim was to address the health needs of frail elderly with multiple social, emotional, physical, and medical problems who were at risk for a custodial admission to acute care. The result was an innovation in organizational and program development that required human, material, and financial resource management to maintain client safety, well being and satisfaction, avert admissions to acute care, and identify new and relevant directions for community healthcare. PMID- 1432225 TI - Implementation of a national nursing standards program. AB - At an annual nursing management conference of a multisystem hospital management firm, nursing executives expressed a need for developing nursing care standards. Because many of the hospitals were small or rural, they lacked some of the resources needed to develop such a program individually. Pooling resources so that all could benefit was an innovative and sensible approach. The authors describe the project that resulted in the development of a nation-wide standards program involving nearly 50 hospitals. PMID- 1432226 TI - The Omaha System. A research-based model for decision making. AB - This article describes the value, diversity, and potential benefits of the Omaha System in generalizing and manipulating client, clinical, and financial data. The authors provide examples of its utility for day-to-day and long-range clinical and financial decision making in home and public health agencies, colleges of nursing, and ambulatory care centers throughout the United States and Canada. PMID- 1432227 TI - Work restructuring: after the decision is made. PMID- 1432228 TI - Work environment factors influencing burnout among third shift nurses. PMID- 1432229 TI - Milestone Action Plans. Empowering nurses to manage care. AB - Confronted by continuing financial losses that could not be simply staunched by further reductions in the operations budget, a medical center implemented an innovative cost-cutting program that offered quick results and simplicity of design while assuring quality patient care. The authors describe the initiative known as Clinical Resource Management (CRM), which unites the expertise of physicians, nurses, and other care providers in a collaborative approach. PMID- 1432230 TI - Characteristics of nursing practice models. AB - Are there differences among the nursing practice dimensions of the three major nursing practice models--team nursing, case management, and total patient care? The author, whose study found few differences, discusses reasons for the similarity among models and suggests approaches to designing future nursing practice models. PMID- 1432231 TI - Job conflict resolution styles of nurses. PMID- 1432232 TI - And the search goes on: the administrative vacancy. PMID- 1432233 TI - Home infusion therapy fact sheet. PMID- 1432234 TI - Improving morale among nurses: ideas for administrators. PMID- 1432235 TI - Trends in nursing administration graduate education. PMID- 1432236 TI - Are dwindling resources affecting the education of nurse administrators? PMID- 1432237 TI - Collaboration in labor relations. A model for success. AB - Proliferation of bargaining units in currently unionized organizations will create new challenges and complexities for nurse executives. Although the literature abounds with strategies to prevent unionization, little had been presented on establishing and maintaining effective relations with bargaining units. The authors focus on currently unionized nursing practice environments and present a model for facilitating positive, cooperative relations between unions, the nursing profession, and the healthcare organization. PMID- 1432238 TI - Fiscal and clinical evaluation of patient care. A case management model for the future. AB - The cost of healthcare within the United States continues to climb as does the number of individuals who have limited access to the healthcare system. By the year 2000, healthcare costs are predicted to comprise 15% of the gross national product. Over the last 10 years, the number of Americans who do not have financial protection from medical costs has risen dramatically. Presently, an estimated 35 million individuals have no insurance or other coverage. PMID- 1432239 TI - Effects of policy manual reorganization on user proficiency. AB - This study compared the proficiency of nurses who located policies in a traditional, alphabetically arranged policy manual vs. a reorganized, indexed manual. Nurses were asked to locate policy statements that would resolve issues presented in three vignettes that were typical of the decisions nurses must regularly make. Answers were scored as correct or incorrect; time to respond and search strategies were also recorded. Data analyses show the overall superiority of the reorganized, indexed manual. PMID- 1432240 TI - Demonstrating excellence in home care through Joint Commission accreditation. AB - Nurse administrators responsible for developing and managing home care delivery systems need to understand the eligibility criteria for accreditation, key components of the standards, survey, and accreditation decision process, and directions for the future including external recognition of accreditation and the use of an indicator monitoring system. The authors highlight the major components and benefits of the home care accreditation program of the Joint Commission on Accreditation of Healthcare Organizations, as well as how the nurse administrator may use accreditation as a valuable management tool. PMID- 1432241 TI - Female nurse executives. Finally, at an advantage? AB - Discrimination, subtle and overt, from socialization and institutional forces, continues to keep nurse executives, most of whom are women, out of chief executive officer (CEO) positions. However, because of the women's movement, changing organizational forces, and shifting demographics, more nurse executives are likely to move into the ranks of CEOs. The authors explore the issues of managerial discrimination and indicate strategies that are beginning to open doors to female nurse executives who desire CEO positions. PMID- 1432242 TI - Inner-city safety for home care providers. AB - For home health agencies to continue serving the elderly and the chronically ill in urban areas, providers must be protected from drugs, weapons, and violence--no easy task in today's environment. What recourse do agencies have short of refusing service? The author discusses what is required to assure safety for providers in the community and for agencies to meet their values, fulfill their missions, and keep healthcare affordable. PMID- 1432243 TI - Obtaining services for HIV-positive patients. AB - Services needed for HIV-positive persons and the availability of these services were reported in the July/August 1990 issue of JONA. This article includes further information from the original study--an analysis of the factors in each reporting hospital and community that enabled or barred the development of services for HIV-positive persons. This information offers strategies to nurse executives for obtaining services in their own settings. PMID- 1432244 TI - Recognizing excellence. Giving your AWE. AB - Nursing and hospital administrators have several methods of recognizing individual achievements. We developed an awards program to recognize excellence for an entire nursing unit. Our Award of Excellence uses rating factors to measure one unit against another. In a much heralded quarterly reception, strongly supported, funded, and attended by senior executives, the staff on the winning unit are complimented for their accomplishment. This program has reduced overtime, while improving productivity and quality of care. PMID- 1432245 TI - Nurse-managed primary care. Tapping the rural community power base. AB - Involving community members into plans and projects is especially salient in initiating and maintaining nurse-managed centers. Nowhere is community involvement more crucial than in establishing a nursing practice in an isolated rural setting. The authors share their first-hand experiences in community interaction in establishing the state-funded health center. PMID- 1432247 TI - Addressing substance abuse within nursing. PMID- 1432246 TI - Establishing an alternate level of care unit. AB - Timely discharge of patients is a major concern of hospitals due to the significant impact of reimbursement constraints. This presents special challenges for hospitals and their staff, who care for an increasing number of elderly patients who do not require acute care, but are waiting for placement in extended care facilities. The authors describe development and economic impact of an alternate level of care unit, that provides an integrated program of services to address the needs of this patient population. PMID- 1432248 TI - Energy expenditure and requirements in aging humans. AB - Although physical activity is frequently recommended for the elderly individual, its influence on energy intake and energy expenditure is unclear. The use of indirect calorimetry techniques and stable isotopes make it possible to examine the effects of physical activity on total daily energy expenditure and its components. In this review, the influence of physical activity on adaptive changes in energy intake, daily energy expenditure, resting metabolic rate and the energy expenditure of physical activity during nonexercising time was examined. Recent findings show that moderate physical activity can increase resting metabolic rate and energy intake in the elderly. Vigorous exercise, however, did not increase total daily energy expenditure because of a compensatory decline in physical activity during nonexercising time. These findings should prompt investigators to re-examine the influence of different levels of endurance exercise on total daily energy expenditure in an attempt to maximize the energy expending properties of physical exercise in older persons. A second objective was to examine the current status of methodology to predict energy requirements in older persons. Current recommendations for energy lack specificity and have not considered the influence of physical activity and body composition. Energy needs of older persons need to be re-examined based on the measurement of total daily energy expenditure. It will then be important to identify biological markers of total daily energy expenditure that take into account the variation in physical activity and body composition. PMID- 1432249 TI - Protective effect of ascorbic acid on the breakdown of proteins exposed to hydrogen peroxide in chicken skeletal muscle. AB - Ascorbic acid is believed to protect cells from oxidative damage by reacting with oxygen-derived free radicals. We investigated whether ascorbic acid would affect the rate of breakdown of skeletal muscle proteins in extracts exposed to hydrogen peroxide. Ascorbic acid (20 mmol/L) alone had little or no effect on the rate of ATP-independent or ATP-dependent breakdown of proteins in chicken skeletal muscle. Pretreatment of chicken skeletal muscle extracts with 10 mmol/L H2O2 resulted in a complete loss of ATP-dependent proteolysis and a significant increase (14- to 15-fold) in the rate of ATP-independent protein breakdown. Ascorbic acid (20 mmol/L) did not prevent H2O2 (10 mmol/L) from inactivating the ATP-dependent proteolytic pathway in skeletal muscle. However, ascorbic acid (20 mmol/L) prevented the H2O2-induced increase in the ATP-independent proteolysis of endogenous muscle proteins. Ascorbic acid also slowed the rate of hydrolysis of exogenously added [3H]superoxide dismutase exposed to H2O2 and inhibited the enhanced degradation of [3H]lysozyme and H2O2-treated [3H]superoxide dismutase by the proteolytic systems exposed to H2O2. Thus ascorbic acid seems to inhibit the H2O2-induced increase in ATP-independent proteolysis 1) by preventing damage to proteins by H2O2 resulting in a decreased supply of substrates for the ATP independent degradative system and 2) by preventing activation of the proteolytic enzymes that participate in the energy-independent degradation of H2O2-treated proteins. PMID- 1432250 TI - Rat hepatic coenzyme A is redistributed in response to mitochondrial acyl coenzyme A accumulation. AB - Coenzyme A without an acyl-thioester (CoASH) is required for numerous cellular reactions, and sequestration of CoASH as acyl-CoAs may impair metabolic function. Increased total CoA protects the cell from acyl-CoA accumulation, and enhanced CoA biosynthesis may represent a compensatory response in metabolic disease. To test the hypothesis that cellular CoA is redistributed from the cytosol to the mitochondria in response to mitochondrial acyl-CoA accretion, the subcellular distribution of hepatic CoA was determined by differential centrifugation and measurement of the mitochondrial marker enzyme citrate synthase. Liver from control, clofibrate-treated and hydroxycobalamin[c-lactam] (HCCL)-treated rats were used. Clofibrate increased total hepatic CoA concentration 2.2-fold, whereas HCCL (which causes inhibition of L-methylmalonyl-CoA mutase and consequent propionyl- and methylmalonyl-CoA accumulation) increased it threefold. However, clofibrate did not affect the percentage of total CoA in the mitochondria (control: 44 +/- 3%, clofibrate: 49 +/- 5%), and HCCL-treatment induced a marked redistribution of CoA into the mitochondria (HCCL: 78 +/- 8%). Redistribution of total CoA was also induced acutely by incubation of hepatocytes from control rats with 10 mmol/L propionate. Thus, redistribution of the cellular CoA pool can help maintain CoASH availability as mitochondrial acyl-CoA accumulation occurs and may be an important compensatory response to metabolic injury. PMID- 1432251 TI - Copper-marginal and copper-deficient diets decrease aortic prostacyclin production and copper-dependent superoxide dismutase activity, and increase aortic lipid peroxidation in rats. AB - Agonist challenged aortic prostacyclin production was examined in copper adequate, -marginal and -deficient rats fed AIN-based diets providing 6.7, 1.7 and 0.8 micrograms Cu/g, respectively. Aortic rings were incubated in Krebs Henseleit salts, 10 mmol/L HEPES buffer, pH 7.4, 95%:5% O2:CO2, 37 degrees C, and equilibrated for 1 h. Equilibrated rings were challenged with buffer (basal), 273.0 nmol/L thrombin and angiotensin II at 84.6 pmol/L and 846.0 pmol/L. Prostacyclin production, determined at 10 minutes by RIA as 6-keto prostaglandin F1 alpha, in basal and 84.6 pmol/L angiotensin II ring incubations was significantly reduced by 28 to 48% in copper-deficient rats. With thrombin or 846.0 pmol/L angiotensin II prostacyclin production was significantly reduced by 18 to 55% in copper-marginal and copper-deficient rats. Copper-dependent superoxide dismutase activity was significantly depressed by 30 and 57% in aortae of copper-marginal and copper-deficient rats. Lipid peroxidation, estimated by the thiobarbituric acid test, was significantly increased by 85% in copper deficient rats, with a nonsignificant 40% increase in aortae from copper-marginal rats. The results suggest that the decreases in aortic prostacyclin production in aortae from both copper-deficient and copper-marginal rats are associated, in a dose-dependent manner, with copper-dependent superoxide dismutase depression and increases in aortic lipid peroxidation. PMID- 1432252 TI - Plasma esterase-1 (ES-1) activity in rats is influenced by the amount and type of dietary fat, and butyryl cholinesterase activity by the type of dietary fat. AB - In previous work, we studied, under conditions of ad libitum food consumption, the effect of amount and type of dietary fat on plasma esterase-1 (ES-1) and butyryl cholinesterase activity in rats. This was done by the isoenergetic replacement of dietary fat by carbohydrates or by another fat source. The observed change in enzyme activity could theoretically be determined by either the dietary omission or the addition or by the combination. In the present work, we studied under restricted feeding conditions the effect of supplemental energy in various forms to determine the effect of the supplement alone. Supplemental coconut fat, but not isoenergetic amounts of either glucose or casein, raised plasma ES-1 activity. None of these supplements influenced butyryl cholinesterase activity. In a second experiment, we demonstrated that the ES-1 enhancing effect of supplemental coconut fat also occurred with fish oil, whereas the stimulatory effects of olive oil and corn oil were less pronounced. Supplemental fish oil, but not the three other fats, significantly reduced the depression in butyryl cholinesterase activity. Plasma cholesterol concentration was negatively associated with butyryl cholinesterase activity, but was not related to ES-1 activity. The two esterases were not correlated with plasma triglyceride concentration. We conclude that both the amount and type of fat in the diet of rats have specific influences on plasma ES-1 activity and that butyryl cholinesterase activity is affected by the type of fat. PMID- 1432253 TI - Copper and selenium deficiencies do not enhance the cardiotoxicity in rats due to chronic doxorubicin treatment. AB - This study tests the hypothesis that Cu and Se deficiencies enhance doxorubicin induced cardiotoxicity and anemia. Male Sprague-Dawley rats (n = 48) were fed Cu and Se-adequate (+Cu+Se), Cu-deficient (-Cu), Se-deficient (-Se) or Cu and Se deficient (-Cu-Se) diets for 5.5 wk. Doxorubicin (4 mg/kg body wt) or saline was administered once weekly for the last 4 wk of the study. Copper deficiency was confirmed by 79% lower liver Cu, 67% lower liver Cu,Zn superoxide dismutase (Cu,Zn SOD) activity and 76% lower erythrocyte Cu,Zn SOD activity. Selenium deficiency was confirmed by 90% lower liver glutathione peroxidase activity. Rats fed the -Cu diet had greater reductions in hematocrit than did those fed the +Cu diet after administration of doxorubicin. Doxorubicin, Cu deficiency and Se deficiency all produced electrocardiographic abnormalities and ultrastructural anatomical lesions. However, the dietary deficiencies did not enhance doxorubicin induced cardiotoxicity. Doxorubicin, but not Cu or Se deficiency, raised lipid peroxidation 16% in liver (P < 0.01) and 18% in heart (not significant). These data suggest that the cardiomyopathies caused by doxorubicin and Cu and Se deficiencies have some similarities, but cardiac changes may be related to mechanisms other than lipid peroxidation. PMID- 1432255 TI - Uptake of lycopene and its geometrical isomers is greater from heat-processed than from unprocessed tomato juice in humans. AB - Lycopene and beta-carotene are the most abundant carotenoids in human blood and tissues. Although lacking provitamin A activity, lycopene may be biologically active by contributing to the antioxidative defense system of the organism. We studied the uptake of lycopene from processed (boiled with 1% corn oil for 1 h) and unprocessed tomato juice in humans. Lycopene concentrations in human serum increased only when processed tomato juice was consumed. Lycopene uptake varied with individuals, but peak serum concentrations were always reached between 24 and 48 h. The carotenoid was eliminated from serum with a half-life of 2-3 d. The increase in peak serum concentrations was dose-dependent but not linear with the dose. Repeated doses led to a continual rise of lycopene in human serum. Of the different geometrical isomers (all-trans, 9-cis and 13-cis), the cis isomers seemed to be somewhat better absorbed than the all-trans form. PMID- 1432254 TI - Modified eggs are compatible with a diet that reduces serum cholesterol concentrations in humans. AB - The National Cholesterol Education Program (NCEP) guidelines recommend dietary restriction of fat and cholesterol to reduce high circulating cholesterol concentrations in adult Americans. Thus, diet counselors recommend consumption of fewer than four egg yolks per week. The present protocol was designed to determine whether the efficacy of an NCEP diet would be reduced by the incorporation of 12 modified eggs per week, and whether the resulting low fat, high cholesterol diet would increase serum lipid concentrations in adults with initial undesirably high (5.17-7.76 mmol/L) concentrations of serum total cholesterol. Feeding a controlled ration to laying hens produced modified eggs that consistently contained more vitamin E and iodine, and more unsaturated fat, than generic eggs. Subjects were randomly assigned to and NCEP diet including either no whole eggs or 12 whole study eggs a week. Ninety-eight subjects completed the parallel study. Subjects in both groups significantly reduced their serum total, LDL and HDL cholesterol (P < 0.001 for total and LDL cholesterol, P < 0.02 for HDL cholesterol) over the 6 wk of study. No significant differences were found between diet groups. We conclude that the study eggs did not adversely affect measured lipid concentrations when added to a low fat diet that favorably alters lipid profiles in hypercholesterolemic subjects. PMID- 1432256 TI - Contribution of skin to whole-body protein synthesis in rats at different stages of maturity. AB - This study assessed whole-body and tissue protein metabolism and the contribution of skin to whole-body protein synthesis during the post-weaning development of rats. Protein fractional synthesis rate was measured in muscle, skin and the whole body of 70-, 160-, 315- and 586-g rats by use of a continuous infusion of L [U-14C]lysine. Rates of protein synthesis were then calculated, based on the tissue free and protein-bound lysine specific radioactivity at the end of the infusion. The fractional protein synthesis rate declined progressively in the skin (from 19.6 to 8.0%/d), in muscle (from 18.9 to 4.8%/d) and in whole body (from 25.0 to 8.5%/d) throughout post-weaning development. Absolute synthesis rates [g/(d.100 g body wt)] of whole-body and muscle proteins decreased by 54 and 50%, respectively. On the other hand, the amount of skin protein synthesized per 100 g body wt was 35% greater in 160-g and 315-g rats than in 70-g and 586-g rats. The absolute synthesis rate of muscle proteins as a percentage of whole body protein synthesis remained fairly constant at a value close to 24%, whereas the skin contribution to whole-body protein synthesis increased from 12% in 70-g rats to 26% in 586-g rats. PMID- 1432257 TI - Comparison of measured carbon dioxide production with that obtained by the isotope dilution technique in neonatal pigs: observations on site of infusion. AB - Fifteen newborn pigs (1.5 kg) were used to estimate CO2 "production" over a 5-h experiment. In each piglet, the average expired air CO2 irreversible loss rate measured over 15-min intervals was compared with an estimate of CO2 "produced" by a continuous infusion of NaH14CO3 into either the aortic artery (seven pigs) or the portal vein (eight pigs). The specific radioactivity (Bq/mumol) of the expired CO2 taken over consecutive 15-min intervals during the 5-h period was fitted to an exponential model to predict the specific radioactivity at steady state. This specific radioactivity was used to calculate the total CO2 irreversible loss rate and to correct for the difference in tracer infused in relation to tracer excreted at 5 h (76 to 78%). The estimated CO2 "produced" tended to be higher (P < 0.12) when the aortal rather than the portal infusion site was used [571 vs. 498 mumol/(min.kg0.75)]. The isotope dilution technique significantly (P < 0.05) overestimated the expired air CO2 regardless of whether the aortal [571 vs. 469 mumol/(min.kg0.75)] or portal [498 vs. 447 mumol/(min.kg0.75)] routes of infusion were used. PMID- 1432258 TI - Evaluation of [1-14C]-medium-chain fatty acid oxidation by neonatal piglets using continuous-infusion radiotracer kinetic methodology. AB - In vivo oxidation rates of systemically infused medium-chain fatty acids were evaluated using neonatal pigs. Unanesthetized piglets (1.6 kg, n = 20) were housed in respiration chambers for total collection of expired CO2 and were continuously infused with [1-14C]-7:0, 8:0, 9:0 or 10:0 fatty acids via a central catheter. The fatty acids were administered at rates of 25, 50 or 100 mumol/min for 5 h and provided 74 kBq of 14C per h. Total expired CO2 was collected over consecutive 15-min intervals for determination of the amount and specific radioactivity of expired CO2. Portal blood samples were drawn from umbilical vein catheters for determination of 3-hydroxy-butyrate and plasma fatty acid concentrations. Infusion and oxidation rates (mmol/min) were multiplied by the molar ATP yield for each fatty acid (i.e., 52, 61, 69 and 78 mmol ATP/mmol fatty acid for 7:0 through 10:0, respectively) to adjust for differences in molar energy content of the various fatty acids. Expressed in this way, fatty acid oxidation rate was proportional to the rate of infusion and accounted for 63% of that infused. The various fatty acids were oxidized equally well, regardless of chain length, and satisfied up to 60 to 70% of the animals' energy requirements, depending on the rate of infusion. These data are discussed in relation to previous work from our laboratory that has shown significant effects of fatty acid chain length on utilization of orally administered medium-chain triglyceride supplements. PMID- 1432259 TI - Lipid peroxidation products are elevated in fish oil diets even in the presence of added antioxidants. AB - Purified corn and fish oil diets with different types and concentrations of antioxidants were evaluated for oxidation products. In addition, a determination of different organ and carcass oxidation product levels was performed. Peroxide value and thiobarbituric acid assays were performed on the diets immediately after mixing (0 h) and 24, 48 and 72 h after being fed to mice. The AIN recommended level of antioxidant addition (butylated hydroxytoluene, 0.02 g/100 g oil) and even the addition of 100 times this level (2 g/100 g oil), although decreasing the level of oxidation products, failed to totally prevent oxidative deterioration in diets high in fish oil. Furthermore, other antioxidants added in excess to the fish oil diets also failed to completely suppress oxidative deterioration of the diets and, in addition, when fed daily to mice for a period of 4 wk, caused an accumulation of lipid peroxidation products in certain organs (e.g., heart, skeletal muscle, mammary glands) and in the carcass. These results provide evidence that in the preparation of fish oil diets, the addition of antioxidants at the AIN-recommended level, or even levels substantially higher, does not completely suppress oxidative deterioration of experimental diets. PMID- 1432260 TI - Dietary sucrose enhances insulin secretion of aging Fischer 344 rats. AB - Male Fischer 344 rats, ages 6, 12 and 26 mo, were fed a diet containing either sucrose or cornstarch (66% by weight) for 4 mo. The effects of age and dietary sucrose on glucose-stimulated insulin secretion were evaluated in whole perfused pancreases and isolated islets of Langerhans, and by intra-arterial glucose administration. In addition, glucose responsiveness of beta-cells was measured by following the rate of glucose oxidation in isolated islets. There was no significant effect of age on glucose-stimulated insulin secretion of whole perfused pancreases and islets of Langerhans. There was, however, a significant main effect of sucrose feeding on insulin secretion. That is, whole perfused pancreases and islets of Langerhans isolated from rats fed sucrose vs. starch diets secreted more insulin in response to glucose. This effect was most pronounced in the 26-mo-old rats. In general, islet glucose oxidation rates, and responses to the in vivo glucose, did not differ among the groups. We conclude that alterations in glucose-stimulated insulin secretion with age more closely reflect changes in diet rather than aging per se. PMID- 1432261 TI - Uptake of 5-formyltetrahydrofolate in isolated rat liver mitochondria is carrier mediated. AB - We have characterized the uptake of 5-formyltetrahydrofolate into isolated rat liver mitochondria. Uptake of 5-formyltetrahydrofolate, 5-methyltetrahydrofolate and folic acid was linear for the first 2 min of incubation. 5 Methyltetrahydrofolate and 5-formyltetrahydrofolate were accumulated in mitochondria to 3.7- and 4.3-fold, respectively. 5-Formyltetrahydrofolate transport showed a pH optimum at 5.5 and was saturable with an apparent Km = 2.80 mumol.L-1 and Vmax = 3.49 pmol.min-1.mg protein-1. Uptake of 5 formyltetrahydrofolate was inhibited by the structural analog 5 methyltetrahydrofolate and, to a much lesser extent, folic acid and methotrexate. Uptake was not inhibited by various substrates of known mitochondrial transporters, e.g., succinate, malate, citrate, glutamate and phosphate, nor was uptake inhibited by the sulfhydryl reagent, N-ethylmaleimide. Uptake was not stimulated by preloading of mitochondria with malate or aspartate. Uptake of 5 formyltetrahydrofolate was not affected by the proton ionophore carbonyl cyanide 4-trifluoromethoxyphenyl-hydrazone nor by collapsing the electrical gradient with valinomycin. These results indicate that 5-formyltetrahydrofolate uptake into mitochondria via a carrier-mediated system specific for the reduced, naturally occurring folates. The folates, once in the mitochondria, may be converted to the polyglutamylated forms, which will not readily diffuse out of the mitochondria. PMID- 1432262 TI - Increasing intake of soybean protein or casein, but not cod meal, reduces nephrocalcinosis in female rats. AB - Female weanling rats were fed diets with soybean protein, casein or cod meal at 171, 342 or 513 mmol nitrogen/100 g for 3 wk. The diets were isonitrogenous and balanced for fat, cholesterol, calcium, magnesium and phosphorus. Cod meal feeding at 171 and 342 mmol nitrogen/100 g diet produced lower kidney calcium concentrations than the feeding of either soybean protein or casein. Increasing protein intakes were associated with reduced kidney calcium concentrations in the rats fed either soybean protein or casein but not in those fed cod meal. The anti nephrocalcinogenic effect of increasing intakes of soybean protein may relate to the lowering of urinary phosphorus concentration. Increasing intakes of casein probably inhibited nephrocalcinogenesis by lowering urinary pH and raising urinary magnesium concentration. Increasing cod meal concentrations in the diet lowered urinary pH and raised urinary magnesium and calcium concentrations, but the effects on nephrocalcinogenesis of these changes probably counteracted each other. PMID- 1432263 TI - Endogenous allantoin excretion in response to changes in protein supply in sheep. AB - Endogenous allantoin derives from the breakdown of tissue nucleic acids. This study examined the effect of changes in protein supply on endogenous allantoin excretion by sheep. The animals were nourished by infusions of volatile fatty acids into the rumen and casein into the abomasum, thus avoiding ruminal microbial fermentation (i.e., no supply of exogenous nucleic acids). While a constant energy supply was maintained, the protein supply was altered in one of two ways: 1) changed from 0 to 3000 mg casein-N/kg metabolic weight (W0.75) per day in progressive steps; or 2) completely removed from an initial constant level [500 mg N/(kg W0.75.d)]. With the first alteration, endogenous allantoin excretion was not directly affected by the daily N input or N retention, but was linearly correlated with the cumulative N retention. With the second alteration, allantoin excretion increased (35-145%) on the first day after removal of the protein supply and then fell to a level equivalent to, or lower than, that before protein removal. The results suggest that the changes in endogenous allantoin excretion may reflect remodeling of the metabolic state of the animal during periods when protein supply fluctuates. PMID- 1432265 TI - Dietary casein and soybean protein affect the concentrations of serum cholesterol, triglyceride and free amino acids in rats. AB - This work was undertaken to investigate the concentrations of free amino acids in blood after food was withheld from growing, male Wistar rats fed cholesterol free, low fat (1 g corn oil/100 g) diets with casein or soybean protein for 2 wk. A diet containing 22.5 or 23.5 g/100 g of soybean protein was hypocholesterolemic compared with a diet containing 20.0 g casein/100 g diet. A comparison of serum amino acids in soybean protein-fed vs. casein-fed rats showed that, whereas concentrations of many amino acids were lower in the soybean protein-fed rats compared with the casein-fed groups, glycine was the only amino acid having a higher concentration. Further, alanine was significantly lower in the soybean protein-fed rats compared with the casein-fed rats, and the protein-induced differences in glycine and alanine concentrations of unfed rats were reproducible. When diets containing 15.0% casein or 30.0% soybean protein, a casein diet supplemented with glycine and a soybean protein diet supplemented with methionine were compared, the changes in serum glycine and alanine correlated with the changes in serum cholesterol. Concentrations of several amino acids, particularly valine, leucine and tyrosine, also changed when serum cholesterol concentrations varied, but these effects could not be explained by our experiments. The results suggest that a change in serum concentration of glycine and alanine of unfed rats may be related to the change in serum cholesterol concentration. PMID- 1432264 TI - Altered zinc metabolism occurs in murine lethal milk syndrome. AB - The lethal milk (lm) mutation in mice causes Zn deficiency in pups nursed by lm dams. To examine tissue Zn distribution and Zn transport to milk and pups, 65Zn was administered to lactating normal and lm dams. Transport of 65Zn to milk of lm dams was approximately 50% of that transported to milk of normal dams. The lower milk 65Zn resulted in significantly less 65Zn uptake by tissues of the nursing pups. The decrease in 65Zn transport to the milk was accompanied by a significant increase in 65Zn uptake and metallothionein mRNA levels in kidney of the lm dams. The elevated Zn uptake and metallothionein expression was tissue specific and could be a reflection of altered zinc transport from mammary gland to milk. Polyacrylamide gel electrophoresis and Western transfer of mammary gland proteins from lm dams showed that a 30-kDa protein bound more 65Zn in vitro compared with proteins from normal mammary gland. Normal pups nursed by dams of the lm genotype had down-regulated metallothionein expression due to Zn deficiency. The genetic defect in lm mice decreases Zn transport to milk, thus explaining the neonatal Zn deficiency seen in normal mice fostered by lm dams. The greater metallothionein expression in dams of the lm genotype could be a secondary manifestation of altered tissue zinc distribution or a primary effect on a metallothionein regulatory mechanism. PMID- 1432266 TI - Fat intake and clofibrate administration have interrelated effects on liver cholesterol concentration and serum butyryl cholinesterase activity in rats. AB - Rats were fed for 15 d purified diets with different amounts of coconut fat, and with or without clofibrate. Fat was added at the expense of an isoenergetic amount of glucose. The hypolipidemic action of clofibrate was not influenced by the amount of fat in the diet. Clofibrate did not affect liver cholesterol concentration in rats fed the low fat diet, but it counteracted the rise in liver cholesterol seen in rats fed the high fat diet. This could relate to the observed raised intestinal clofibrate-hydrolyzing activity of rats fed the high fat diet, because hydrolysis of clofibrate gives rise to its biologically active form. In rats fed the low fat diet, but not in those fed the high fat diet, clofibrate raised the activity of serum esterase-1, which (unlike esterase-2) does not hydrolyze clofibrate. Possibly, the dramatic stimulatory effect of fat feeding on serum esterase-1 activity had overruled any influence of clofibrate. Clofibrate elevated serum butyryl cholinesterase activity, with this effect being amplified by fat feeding. High levels of dietary fat in the absence of dietary clofibrate did not alter serum butyryl cholinesterase activity. Clofibrate did not change butyryl cholinesterase and esterase-1 activities in small intestine. The high fat diet caused slightly higher levels of butyryl cholinesterase activity in small intestine, but markedly raised intestinal esterase-1 activity. This study shows that certain effects of clofibrate and a high fat diet are interrelated. PMID- 1432267 TI - Structure of dietary pectin, iron bioavailability and hemoglobin repletion in anemic rats. AB - The effects of the degree of esterification (DE) and the molecular weight (MW) of pectins on iron bioavailability were investigated in anemic rats. The pectins prepared differed (in DE and MW, respectively) as follows: P-A (73%, 860,000), P B (75%, 89,000), P-C (22%, 1,260,000) and P-D (24%, 114,000). Rats were fed an iron-deficient diet (8 mg Fe/kg diet) for 14 d. The anemic rats were then fed a ferrous sulfate-supplemented basal diet (47 mg Fe/kg diet) or the basal diet containing one of the pectins (80 g/kg diet) for 10 d. None of the pectins used caused any significant reduction in the bioavailability of ferrous sulfate. Addition of pectin P-B to the diet resulted in significantly greater iron repletion. Compared with control rats fed with ad libitum access or pair-fed, rats fed P-B showed higher (P < 0.05) hemoglobin regeneration efficiency, hematocrit, serum iron concentration, and transferrin saturation, and lower unsaturated iron-binding capacity and total iron-binding capacity. Pectins P-A and P-D also slightly improved the hematological indices compared with P-C and control. The observed effects were dependent on the physicochemical properties of each pectin as determined by its MW and DE. PMID- 1432268 TI - A longitudinal study of nurses' attitudes toward caring for patients with AIDS in Erie County. AB - The purpose of this study was to examine nurses' attitudes toward caring for patients with AIDS in a longitudinal context. Results of the 1990 survey were compared with those of a survey conducted in 1986 for the purpose of examining changes in attitudes over time. Findings indicated that there were no significant differences between the 1986 and 1990 scores on the attitude scales. The results of the study indicated that many nurses still have fears and concerns about caring for patients with AIDS. PMID- 1432269 TI - American nursing: 100 years of conflicting ideas and ideals. AB - Based on historical research about nursing sponsors, actors, activities, preparation, and location of work, this paper identifies divisive themes that have recurred in American nursing throughout its history. The conflictive areas discussed are: ideals, gender, the search for status and the use of exclusion, the merger of training and practice, and the differences between ordinary nurses and nursing leaders. PMID- 1432270 TI - Theory construction and development. PMID- 1432271 TI - Survey of nursing research in NYS: XIV. PMID- 1432272 TI - What is nursing research: evolving approaches to methods and content. AB - In addressing what constitutes nursing research in the 1990s, approaches to conducting nursing research and examples of studies are discussed in the context of historical forces. The early studies were characteristically educational in focus and quantitative by design. Nursing research has come a long way in regard to foci of the questions asked, diversity of approaches to knowledge development, and sophistication of research methods. Three approaches are described to illustrate the diversity in nursing research: quantitative, qualitative, and triangulation. PMID- 1432273 TI - Perinatal outcome for women in prison. AB - Pregnancy outcome for 233 women in prison was reviewed. This group of patients presented with multiple perinatal high-risk factors: history of illicit drug use (71%), smoking (70%), and obstetrical (27%), medical (21%), nutritional (20%), and infectious complications (20%). Maternal morbidity was uncommon and the overall cesarean section rate for all prisoners was 16%. There was 1 stillbirth and 236 live-born infants, all of whom were discharged in good health. Prematurity (3%) and delivery of small-for-gestational-age (SGA) (8%) infants was less common among 187 women who received adequate prenatal care than in 46 prisoners with poor or late prenatal care (prematurity 20% and SGA 28%). Good perinatal outcome for women in prison can be achieved if comprehensive prenatal care is available. PMID- 1432274 TI - Thromboxane synthetase inhibition produces maternal and fetal vasodilation during ovine pregnancy-induced hypertension: a Doppler flow velocimetric study. AB - Changes in maternal and fetal umbilical arterial vasoreactivity during ovine pregnancy-induced hypertension and following intravenous administration of CGS 12970 [3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid] were assessed. Continuous wave Doppler flow velocimetry was used to assess vascular reactivity during normotensive baseline, during ovine pregnancy-induced hypertension triggered by a 72-hour fast, and following thromboxane synthetase inhibition with CGS 12970. Uterine and umbilical arterial systolic/diastolic flow ratios increased significantly with the onset of sustained hypertension. After thromboxane synthetase inhibition, uterine and umbilical artery systolic/diastolic flow ratios were not different from baseline, and maternal blood pressure had returned to baseline values. These data indicate that thromboxane produces maternal and fetal vasoconstriction during ovine pregnancy-induced hypertension. Furthermore, these data provide strong evidence that thromboxane synthetase inhibition allows vasodilation, resulting in improved maternal and fetal condition. PMID- 1432275 TI - Is cord blood erythropoietin a marker of intrapartum hypoxia? AB - A sensitive assay was used to compare the biological activity of cord serum erythropoietin in two groups of infants born with or without labor-induced hypoxia. The mean cord serum erythropoietin activity in 161 infants delivered after vaginal labor was 116 +/- 36 mU/mL, and was indistinguishable from that observed in 23 infants delivered by preplanned, elective cesarean section, 114 +/ 12 mU/mL (P = .75). The bioassay measured effective erythropoietin activity, including the contribution of potentiators in serum. These results indicate that duration and intensity of labor are insufficient to cause a significant increase in effective erythropoietin activity. PMID- 1432276 TI - Perinatal toxicology screening. AB - Accurate identification of substance abusing mothers and their infants is critical for appropriate medical management as well as the collection of accurate information on the effects of illicit drug use on perinatal morbidity, mortality, and long-term neurobehavioral outcome in the infants. This study examines the differences found using two methods for urine toxicology screening at the time of obstetrical admission to the hospital. The institution of universal screening identified significantly more women than were previously identified through the use of a risk-directed protocol (P less than .0001). Women identified using either protocol were significantly more likely than toxicology-negative women to have had poor prenatal care and to have smoked and used alcohol during pregnancy (P less than .001). In the population studied, the multiple criteria needed to accurately identify mothers with positive-toxicology screens would also include screening over one half of the toxicology-negative mothers. PMID- 1432277 TI - Congenital complete heart block associated with maternal anti-Ro antibody: a case report. AB - The presence of anti-Ro antibody in maternal serum is a serologic marker for increased risk of the development of congenital complete heart block in the fetus. Current etiology and evaluation of these mothers and their fetuses are examined. A case report is presented. PMID- 1432278 TI - Sudden fetal death in women with well-controlled, intensively monitored gestational diabetes. AB - An intensive antepartum monitoring system for women with gestational diabetes mellitus was evaluated over a 5-year period. Early diagnosis and liberal treatment with insulin was concomitantly followed with non-stress testing: weekly from 28 to 34 weeks' gestation and semi-weekly thereafter. Despite maternal euglycemia and satisfactory antepartum assessment, three fetal deaths occurred within 72 hours of reassuring fetal monitoring. Additionally, 24 (7%) fetuses were delivered on the basis of a low biophysical profile score (less than 6) at term. The stillbirth rate for women with gestational diabetes was 7.7/1000, whereas the stillbirth rate for nondiabetic low-risk patients was 4.8/1000. Women with gestational diabetes continue to be in a high-risk category for antepartum fetal death, requiring intensive monitoring with consideration for timely delivery. PMID- 1432279 TI - Transient hyperammonemia of the newborn: a vascular complication of prematurity? AB - Transient hyperammonemia of the newborn is an overwhelming disease manifested by hyperammonemic coma in ill premature infants. A summary of evidence is presented supporting the hypothesis that this syndrome is a vascular complication caused by shunting of blood away from the portal circulation of the liver into the systemic circulation with subsequent lack of ammonia removal. Alternative, nontraditional approaches of investigation and therapy targeting the hepatic portal circulation should be explored in patients with transient hyperammonemia of the newborn. PMID- 1432280 TI - Waxing and waning hyperinflation in congenital cystic adenomatoid malformation of the lung. AB - This report describes a newborn with respiratory distress, waxing and waning left lung hyperinflation, and pulmonary hemorrhage. This atypical presentation of congenital cystic adenomatoid malformation of the lung has not been previously reported, posed a major diagnostic problem, and delayed potentially lifesaving surgery. PMID- 1432281 TI - Limitations in the usefulness of urine latex particle agglutination tests and hematologic measurements in diagnosing neonatal sepsis during the first week of life. AB - We present findings regarding the usefulness of urine latex particle agglutination (LPA) testing for group B streptococcus (GBS) antigen, as well as hematologic values, in diagnosing sepsis during the 1st week of life. Of 475 inborn neonates evaluated, 27 (5.7%) had confirmed sepsis, 47 (9.9%) had indeterminate findings precluding further classification, and 401 (84.4%) were not septic. We examined the following: (1) total white blood cell count (WBC); (2) total polymorphonuclear leukocytes (PMNs); (3) total immature PMNs; (4) immature to total (I:T) neutrophil ratio; (5) immature to mature (I:M) neutrophil ratio; (6) platelet count; (7) a 6-point hematologic score based on the preceding values; and (8) urine LPA for GBS. The positive predictive values of the six hematologic values, as well as the hematologic score, were disappointingly low. Using higher I:T ratios (greater than or equal to 0.30 or 0.40) marginally increased the positive predictive values. More than 60% of our ill, nonseptic neonates had I:T ratios greater than or equal to 0.20. Of 15 infants with culture proven systemic (blood or cerebrospinal fluid) GBS infection who were tested with urine LPA for GBS antigen, only 4 had positive results. Nineteen infants had positive urine LPAs with concomitant negative blood cultures. Urine cultures were obtained from 18 of these infants. No organisms were isolated from any of these specimens. The mothers of 7 of the infants with positive LPAs and negative blood cultures had received intrapartum antibiotics. Of the remaining 12 infants, the urine LPA was repeated in 8 and results were negative in each case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432282 TI - Effects of dexamethasone on pulmonary function following extubation. AB - Dexamethasone is often given to intubated neonates to facilitate successful extubation. To study the effects of dexamethasone on pulmonary function immediately following extubation, we conducted a randomized, blinded, placebo controlled trial in 51 infants. All infants had been intubated for a minimum of 3 days but no more than 30 days. Mean weight at extubation was 2.41 kg in treated infants, 2.25 kg in control infants. When infants were deemed ready for extubation, dexamethasone 0.5 mg/kg/dose or an equal volume of normal saline was given in three doses 8 hours apart. The final dose was given 1 hour before extubation. Esophageal pressure, air flow integrated to tidal volume (Vt), respiratory rate, and heart rate were measured before extubation, immediately following extubation, and every 20 minutes for 80 minutes. Total pulmonary resistance (RTP), dynamic lung compliance (CL), and minute ventilation (VE) were calculated. Forty-two infants completed the study; 19 infants received dexamethasone and 23 received placebo. There was no difference between the two groups in gestational age, weight at study, or length of intubation. Vt, RTP, VE, and CL were not significantly different between the two groups over time; however, RTP increased over time in the placebo group. Heart rate was significantly lower in the dexamethasone group. We conclude that dexamethasone appears to have limited effect on pulmonary function immediately following extubation in the population studied. Further studies should evaluate the drug effect beginning at least 1 hour after extubation. PMID- 1432283 TI - Magnetic resonance imaging in full-term infants with repetitive focal seizures. AB - We report two full-term infants who developed repetitive focal seizures within the first 48 hours of life. Neither infant had predisposing factors and there were no abnormalities on a computed tomography (CT) scan performed on day 2 of life. Magnetic resonance imaging (MRI) performed during the second week of life showed a focal hemorrhagic infarction in both patients. We conclude that either an MRI or a contrast-enhanced CT scan should be obtained within 1 week in patients in whom the initial imaging technique failed to reveal a focal lesion, at which time a cerebral infarction can be diagnosed with greater sensitivity. PMID- 1432284 TI - Emotion in women undergoing amniocentesis in the second trimester of pregnancy. AB - A descriptive study was conducted to determine the emotions of women at three points during the amniocentesis process. A volunteer convenience sample of 60 women who were undergoing a first amniocentesis in the second trimester of pregnancy participated in the study. Participants completed a demographic and an amniocentesis information survey upon entry into the study. An emotion scale was administered at three specific times. Results showed that positive emotions increased significantly as the process unfolded. Some negative emotions decreased over time. Correlation of the information score and the emotion score demonstrated no significant relationship between these variables. PMID- 1432285 TI - The loss of a dream. Perinatal loss or an unexpected pregnancy outcome. PMID- 1432286 TI - The high-risk infant environment. Part 2. The role of caregiving and the social environment. AB - Neonatal intensive care units are essential for the successful care of very immature and sick infants. The technology of NICUs has contributed significantly to the reduction of neonatal mortality and improvement of neonatal outcome. While the outcome for high-risk neonates has vastly improved over the past three decades, a number of infants sustain injuries and complications that result in long-term disabilities. It is now clear that some of the long-term problems of high-risk infants are a result of the environment and care practices and are not attributable to the original disease or condition that necessitated intensive care. There is accumulating evidence that environmental factors and care practices can interact with disease processes in ways that can increase morbidity, and possibly mortality. In addition to developmental and behavioral problems, there is growing evidence of effects on visual function and perhaps other sensory systems. Many of the environmental and care factors may cause delay in recovery and increase NICU time or unnecessary discomfort, yet not produce long-term disabilities or problems, as currently assessed. Many of the potential behavioral and developmental problems, as well as many of the potential problems with visual, auditory, and other modes of sensory discrimination, are not included in the usual follow-up assessments. The absence of data or the limitations of existing studies are not a cause for comfort or the assumption that the environment and care practices are safe or not harmful.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432287 TI - Effects of transcutaneous monitor electrode heat on skin servo-controlled environments. AB - This study tested the hypotheses that (1) the heat generated by a transcutaneous monitor electrode is sufficient to decrease skin servo-controlled radiant warmer heat output when it is positioned next to the operating skin servo-thermistor, and (2) the decrease in radiant warmer heat output is enough to lower body temperatures or cause a heat-conserving response in a baby. Seventeen newborns less than or equal to 5 days old, gestational age 29 to 40 weeks, cared for under radiant warmers were studied before and for 30 minutes after juxtaposition of the transcutaneous monitor electrode and the skin servo-controlled thermistor. Mean radiant warmer heat output, measured as watt-hours/5 minute periods, decreased for the first 15 minutes after movement, mainly in the infants cared for under an older model radiant warmer. Mean skin temperature and foot temperature decreased, and esophageal-foot temperature gradient increased for those under the older model radiant warmer. Despite differences in the gestational age of the infants under the older compared with the newer model radiant warmer, multiple regression analysis indicated a significant effect of the model of radiant warmer on the results. Many factors can influence the proper functioning of servo-controlled heating systems, including the type of electronic logic and extraneous sources of heat. These factors require more study, and should be considered in the evaluation of thermal control problems. PMID- 1432288 TI - Sudden deterioration of intubated newborn: four steps to the differential diagnosis and initial management. AB - This paper provides guidelines to determine the differential diagnosis and treatment of sudden deterioration of an endotracheally intubated newborn infant. Since such an event is most often secondary to a mechanical problem, simple adjustment of the ventilator in response to blood gas analysis will only rarely be sufficient to stabilize the infant. The proposed algorithm integrates history, physical examination, investigations, and therapeutic intervention (of which manual ventilation is the keystone). We hope that such an algorithm may help training physicians, nurses, and respiratory therapists to minimize the risk for the infant as well as the time required to provide an efficient resuscitation. This algorithm may be used both in the neonatal intensive care unit and in the delivery room as a complement to the recommendations of the American Heart Association, in case of poor response to the resuscitation. Modifications to this protocol should be allowed according to specific characteristics of each infant and to the equipment available. PMID- 1432289 TI - Decreased fetal movement with abnormal nonstress test preceding fetal death. PMID- 1432290 TI - Topics in neonatal nutrition. Early ileostomy closure to prevent chronic salt and water losses in infants. PMID- 1432291 TI - An interesting case presentation: a possible new route for perinatal acquisition of Chlamydia. AB - Chlamydia trachomatis is currently the most common sexually transmitted disease in the United States. The prevalence in pregnant women ranges between 2% and 47%. It is well known that C trachomatis can be transmitted from the genital tract of an infected mother to her newborn infant, causing conjunctivitis or pneumonia or both, along with their longstanding complications. A review of the literature failed to show, however, conclusive evidence of transmission of infection to the newborn infant when the infant was born by cesarean section with intact amniotic membranes. We present a case of a young black woman with a history of chlamydia cervicitis during pregnancy whose infant was delivered by cesarean section because of failure to progress. She gave birth to a healthy term infant who developed ophthalmia neonatorum on the 3rd day of life. Examinations of conjunctival scrapings with direct fluorescent staining (chlamydia MicroTrak) performed on the 1st and 3rd day of life were positive. The initial test was performed because of the maternal history. The infant was mildly symptomatic at the time the study was repeated for confirmation. Our findings strongly suggest the possibility of either transmembrane or transplacental route of infection in the pathogenesis of neonatal chlamydia infection. Further study is needed to confirm this possibility. PMID- 1432292 TI - Legionella pneumophila in a preterm infant. A case report. PMID- 1432293 TI - Hypoplastic left heart syndrome: access to medical care. PMID- 1432294 TI - The effectiveness of preemployment drug screening in the prediction of employment outcome. AB - Studies of adverse employment outcomes associated with positive preemployment drug screens have tracked employees for only about 1 year. Changes in drug use after hire may invalidate the predictions of employment outcome in later years which are essential for cost-benefit analyses. This blinded, prospective cohort study tracks absence, industrial accidents, occupational injuries, discipline, and turnover in 2537 screened employees through an average of 2 years. Marijuana positive urines predicted increased turnover, accidents, injuries, discipline, and absence, but these risks appeared lower in the second year than the first. Cocaine-positive urines predicted increased turnover, accidents, injuries, discipline, and absence at levels not consistently different than the first year. Cost-benefit analyses of drug screening project employment risks throughout employees' careers. This study raises the possibility that elevated risks may decrease after the first year. PMID- 1432295 TI - An investigation of a workplace cluster of Bell's palsy. AB - We undertook a study to confirm the existence of an apparent cluster of Bell's palsy in an industrial plant ("W4"), and to test etiologic hypotheses regarding chemical exposures, immune suppression, and infectious etiologies. Cases were enumerated by questionnaire. Employees with a history of Bell's palsy ("cases") were invited to participate in a study that included medical history, T cell studies, viral and Lyme disease serologies, and blink reflex studies. Thirty three unaffected volunteers from W4 and 32 from a comparison building were also tested. Extensive environmental studies were carried out in W4, evaluating infectious, chemical, and radiation exposures. The lifetime incidence of self reported Bell's palsy was 11.6/10,000 person-years (P-Y) in W4 and 2.4 cases/10,000 P-Y in the comparison building (RR = 4.8, P < .05); the comparison rate was similar to that reported in previous population studies. When restricted to cases occurring after the onset of work, the W4 incidence was 29.2 cases/10,000 P-Y, compared to 4.8 cases/10,000 P-Y in the comparison building (RR = 6.1, P < .05). The cases and noncases did not differ with respect to clinical histories or infectious disease titers. The W4 noncases had small but significant decreases in T lymphocyte (1974 +/- 86 vs 2291 +/- 103) and CD4 (1083 +/- 318 vs 1459 +/- 494) counts compared to the remote noncases. The cases had significantly prolonged RR1, LR1, and LFC values compared to both groups of noncases. No medical or environmental factors were identified that could explain an excess of disease. PMID- 1432296 TI - Factors associated with adherence to breast cancer screening among working women. AB - This study identified sociodemographic, knowledge, attitude, and social influence correlates of obtaining mammograms among employed women age 40 and over. Telephone interviews were conducted with 798 women who worked at 39 different work sites. Eighty-four percent of respondents had ever had a mammogram, and 72% had had one at the recommended interval for their age group. The only personal characteristic that was associated with past mammography use was having a co worker, friend, or relative with a history of breast cancer. Logistic regression analyses indicated that a doctor's advice to have a mammogram, knowledge of screening guidelines, knowing someone with breast cancer, and the beliefs that mammography is effective and that mammography is necessary in the absence of symptoms were associated independently with past use of mammography. Three factors contributed independently to explaining adherence to mammography guidelines: younger age, knowledge of guidelines for one's own age group, and the belief that breast cancer is curable. The findings suggest that emphasizing the recommended guidelines, the need for and benefits of mammography in educational programs, and offering low-cost or free mammography at the workplace, can further increase appropriate utilization among working women. PMID- 1432297 TI - Use of PCB blood levels to assess potential exposure following an electrical transformer explosion. AB - Following the explosion of a transformer, passersby, building occupants, and cleanup personnel had potential exposure to the transformer dielectric fluid containing polychlorinated biphenyls (PCBs). As part of a medical evaluation, blood serum was analyzed for PCBs, and the concentrations found were similar to that of a regional comparison group (median 4.0 ng/mL or parts per billion, range 1-10, n = 60). Some workers employed by the utility company that owned the transformer had potential exposure to PCBs in the past. This positive comparison group had significantly higher serum PCB concentrations, related to known direct contact (median 5.0, mean 14 ng/mL, 1-187, n = 25) or not (median 4.0, mean 11 ng/mL, 2-72, n = 17). Therefore, in this investigation, elevation of serum PCB levels could be related to past contact during work with transformers, but not to potential short-term exposure at the time of a transfer explosion. PMID- 1432298 TI - Occupational reintegration of long-term cancer survivors. AB - To determine the long-term psychosocial consequences of cancer related to work, a postal survey was conducted among 849 long-term survivors of cancer in the southwest Netherlands. Forty-four percent of the responders who worked at the time of the diagnosis of cancer returned to their job, 24% of them part-time. Fourteen percent experienced impediments at work after return. Absenteeism in this group does not differ from that in the year prior to the moment of diagnosis. There is a small decrease in promotional and financial prospects. PMID- 1432299 TI - Comparison of mother's occupation and industry from the birth certificate and a self-administered questionnaire. AB - Maternal occupations recorded on birth certificates are a potential data source for evaluation of reproductive hazards, but may not accurately identify jobs held during the sensitive first trimester. Mothers' occupation and industry during 1 month before and 3 months after conception were reported on 1,760 mailed questionnaires. These were compared to mothers' most recent occupation and industry recorded on birth certificates. Overall, 72% of occupations and 77% of industries reported on the birth certificate agreed with that recorded on the questionnaire. Agreement was similar for mothers of normal and malformed infants. Among those that did not agree, 344 (75%) disagreed on the mother's employment status during the periconceptional period, rather than the actual occupation. For surveillance and hypothesis-generation using birth certificate data, it is important to obtain a correct description of whether the mother held a job outside the home during sensitive periods of her pregnancy. PMID- 1432300 TI - Mushroom worker's lung. Detection of antibodies against Shii-take (Lentinus edodes) spore antigens in Shii-take workers. AB - Indoor cultivation of the edible mushroom Shii-take (Lentinus edodes) regularly leads to symptoms of mushroom worker's lung (MWL) in workers. An immunologic test is described allowing detection of IgG type antibodies against Shii-take spore antigens. It was found that MWL patients employed in Shii-take picking (n = 5) have significantly increased antibody titres against Shii-take spore antigens. Different control groups, viz, MWL patients employed in the cultivation of the white button mushroom Agaricus bisporus (n = 14) and of the oyster mushroom Pleurotus spp (n = 3), patients with Bechterew's syndrome (n = 7), sarcoidosis (n = 7), rheumatoid arthritis (n = 9), and healthy controls were found in the same range of low titres. The use of protective masks during picking reduced complaints of the workers (n = 14). However, their antibody titres increased with duration of employment despite the protection. PMID- 1432301 TI - Streptococcus suis meningitis. A severe noncompensated occupational disease. AB - Meningitis caused by Streptococcus suis type 2, a rare disease first recognized in 1968 (108 cases worldwide in 1989), is contracted by occupational exposure to pigs and often results in very severe disabilities (definitive deafness and ataxia in 50% of cases). We report the case of an employee in a rendering plant whose initial symptom was deafness. A detailed analysis of medical and veterinary literature is provided concerning the epidemiology of the disease, the clinical forms in man, bacteriological diagnosis and the role of the pig as healthy carrier. It is recommended that this occupational disease be officially recognized for compensation in France. PMID- 1432302 TI - Cognitive dysfunction in a patient with long-term occupational exposure to ethylene oxide. Role of ethylene oxide as a causal factor. AB - This case illustrates a comprehensive approach to assessing causality in a woman with apparent cognitive dysfunction, as measured by neuropsychological testing, and a 10-year history of occupational exposure to ethylene oxide. The analysis included a multidisciplinary examination of the patient, which took place several years after the termination of her exposure. In addition, all of the patient's prior medical and psychiatric records were reviewed, as were the records of her employer to ascertain her exposure history. Our evaluation revealed a pattern of neuropsychological findings not consistent with nervous system damage secondary to an organic effect of ethylene oxide. A more likely causal hypothesis is adopted: the patient's apparent cognitive dysfunction had a psychiatric etiology. This case also illustrates the potential impact of a patient's involvement in legal proceedings related to claims of neurocognitive dysfunction. PMID- 1432303 TI - Authors' commentary. EtO is associated with cognitive dysfunction. PMID- 1432304 TI - Risk factors for carpal tunnel syndrome in industry: blaming the victim? PMID- 1432305 TI - Arm pain in the workplace. PMID- 1432306 TI - Work coding. PMID- 1432307 TI - Micro-architecture and composition of artery walls: relationship to location, diameter and the distribution of mechanical stress. AB - PURPOSE: We reviewed the structural basis of the mechanical properties of the arterial wall, in order to establish a coherent micro-anatomical basis for the differences in compliance among different arteries and a framework for assessing changes in the mechanical properties of specific individual arteries in relation to changing physical stresses. DATA IDENTIFICATION: The data and concepts presented here were derived from both earlier and ongoing work. Features that assure stability and integrity in relation to blood flow (wall shear stress) and pressure (mural tensile stress) were examined. Particular attention was paid to the morphogenetic and biosynthetic means by which arteries adapt to normal or abnormal modifications of these forces, particularly in relation to growth, location in the arterial tree and geometric configuration. RESULTS AND CONCLUSIONS: Thickness, composition and architecture of the artery wall, including thickness and composition of the intima, are normally determined by the stresses imposed by pressure and flow. Vessel radius is closely associated with flow, so that a normal baseline level of mean shear stress of about 15 dyn/cm2 is maintained or restored. Wall thickness and composition are determined by wall tension in relation to pressure and radius. Baseline levels of tensile stress differ with location but appear to be similar for homologous vessels. Changes in flow that modify the radius also modify wall tension. Changes in wall thickness and composition are likely to cause changes in compliance, due to altered flow and/or pressure patterns; these changes in compliance may be adaptive rather than destructive. Changes in the compliance of specific arteries over time may be used to evaluate the progression and severity of the conditions underlying these changes. PMID- 1432308 TI - Dynamic non-invasive measurements of arterial diameter and wall thickness. AB - AIM: Non-invasive measurements of arterial diameter and wall thickness are critical in characterizing the onset and development of vascular disease. A precise dynamic method was proposed and tested for this purpose. DESIGN: A non invasive method of measuring the variations in diameter and thickness of human arteries throughout the cardiac cycle was developed, using a high-precision ultrasonic echo-tracking system. An adaptive filtering technique was used to suppress artefacts caused by the layered tissue structure of the vessel wall. RESULTS: Based on decorrelation of microstructure noise, this technique improved the detectability of the wall interfaces, which allowed a determination of thickness and diameter. The accuracy and reproducibility of the method were tested by measurements of plastic films with known thicknesses. The discrepancies between standard micrometer and pulse-echo measurement were consistently less than 5 microns for film thicknesses ranging from 220 to 800 microns. The difference between two successive measurements was less than 2 microns. The identity of the measured vascular interfaces was checked in two ways. First, experiments on fixed bovine carotid arteries showed that the identified echogenic interfaces corresponded to the actual anatomical structure, as obtained by acoustic microscopy. Second, the radial artery thickness and diameter were extrapolated to obtain the change in wall volume over one cardiac cycle. The volume was found to be nearly constant, indicating incompressibility. CONCLUSION: This method will make it possible to obtain new information on atherogenesis and other vascular diseases. PMID- 1432309 TI - First- and third-order models for determining arterial compliance. AB - BACKGROUND: Engineering models of the arterial vasculature have been used to describe vascular properties of resistance and compliance. These approaches have used either Fourier frequency analysis, based on transmission line equations, or time domain analysis of the circuit equations describing modified Windkessel models of the vasculature. DESIGN: A third-order, four-element modified Windkessel model can reproduce arterial pressure waveforms, including both exponential and oscillatory pressure decays observed during the diastolic portion of the cardiac cycle. METHOD: A method to determine both capacitive and oscillatory compliance of the arterial vasculature was developed, and the effect of these compliance properties on the blood pressure waveform was examined. PMID- 1432310 TI - Incompressibility of the human arterial wall: an in vitro ultrasound study. AB - AIM: The assumption that the arterial wall behaves like incompressible material simplifies the analysis of arterial wall elasticity. Experimental evidence for the incompressibility assumption has been obtained directly by volume displacement and radiological methods. Recent developments in ultrasound technology have made it possible to take direct, high-resolution measurements of the internal diameter and wall thickness of an artery and thus calculate the cross-sectional area of the arterial wall. The objective of this study was to determine the cross-sectional area of the arterial wall in vitro at different levels of strain in order to demonstrate the incompressibility assumption. METHODS: Two different types of fresh, human, medium-sized arteries were studied, the internal mammary artery, and a less elastic and more muscular artery, the radial artery. The internal diameter and wall thickness were measured with an ultrasonic echo-tracking device (NIUS 1; Asulab, Neuchatel, Switzerland) over 1 min steps of increasing intra-arterial pressure (0, 50, 100, 150 and 175 mmHg). RESULTS: The cross-sectional area of the arterial wall of the radial and internal mammary artery remained unchanged under different levels of strain. CONCLUSION: Since the artery length remained constant during the pressure increases, the lack of change in the cross-sectional area of the arterial wall suggests that the arterial wall of human medium-sized arteries is essentially incompressible. PMID- 1432311 TI - Non-invasive measurements of arterial compliance in hypertensive compared with normotensive adults. AB - AIM: To determine differences in arterial compliance attributable to hypertension. METHODS: Since measurements of arterial compliance have tended to vary in the past according to the method used, a new technique comprising carotid ultrasound and simultaneous, calibrated, carotid pressure waveform measurements was tested in 43 hypertensives and 43 control subjects matched for age, gender and body size. RESULTS: There was a significant reduction in compliance among the hypertensive patients, as estimated by the elastic modulus and the ratio of stroke volume to pulse pressure. However, when the non-linearity of the pressure volume relationship and the impact of distending pressure were taken into account, by the arterial stiffness index and by the increase in arterial wall thickness associated with hypertension by Young's modulus, there were no significant differences in arterial compliance between the two groups. PMID- 1432312 TI - Conclusions on the measurement of arterial wall thickness: anatomic, physiologic and methodologic considerations. AB - AIM: To discuss the use of new ultrasonic techniques that make it possible to visualize elastic (carotid) and muscular (radial) capacitance arteries non invasively. RESULTS OF DATA REVIEW: Measurements of carotid wall thickness and the detection of atheromas are related to arterial pressure, to other risk factors and to the risk of subsequent complications. The use of high-frequency ultrasound (7.5-10 MHz), measurements of far wall thicknesses in areas free of atheromas at end-diastole (by ECG gating or pressure waveform recording) and descriptions of the size and characteristics of atherosclerotic plaques allow a non-invasive assessment of vascular hypertrophy and atherosclerosis in hypertensive patients. CONCLUSIONS: Careful attention to methodologic and physiologic factors is needed to provide accurate information about the anatomy of the dynamically pulsating arterial tree. PMID- 1432313 TI - Introduction to large artery properties as a target for risk reduction by antihypertensive therapy. AB - AIM: To review the effect of antihypertensive drugs on pulsatile stress and shear stress. RESULTS OF DATA REVIEW: Mortality and morbidity in hypertension are better correlated with systolic than diastolic blood pressure, indicating a pulsatile stress effect. Distensibility and compliance are large artery properties and important determinants of pulsatile stress. beta-Blockers with vasodilating properties, several selective beta 1-blockers, angiotensin converting enzyme inhibitors and calcium antagonists are first-line antihypertensive drugs that improve these properties of large arteries. The impact of shear stress on the ill effects associated with hypertension is not clear. CONCLUSION: Some but not all classes of antihypertensive drugs can improve large artery properties, and thereby alleviate pulsatile stress. PMID- 1432314 TI - Physiological and pharmacological changes in the carotid artery pressure-volume curve in situ in rats. AB - AIM: To measure the mechanical properties of the rat carotid artery as affected by physiological and pharmacological changes. METHODS: We used an in situ measurement method that did not affect the anatomy, vascularization or innervation of the carotid artery, in normotensive and in spontaneously hypertensive rats (SHR), to evaluate the effects of ageing, hypertension and acute or chronic drug-induced vasorelaxation. RESULTS: The compliance-pressure curve was characterized, under baseline conditions, by two phases, an ascending component in the lower pressure ranges and a descending component in the higher pressure ranges. In younger or older normotensive rats the maximum value of carotid compliance was observed for values of transmural pressure that approximated those of the operating mean blood pressure. For any given value of transmural pressure, carotid compliance was lower in the hypertensive rats, whether younger (3 months) or older (18 months), than in normotensive rats. This finding was particularly striking for transmural pressures below 125 mmHg, and held true even after the administration of potassium cyanide. Consequently, the reduced compliance in the hypertensive rats was attributed predominantly to structural changes in the arterial wall. Moreover, in the hypertensive rats there was a dissociation between the operating arterial blood pressure level and the maximum value of carotid arterial compliance. Thus in young SHR, whereas the operating systemic blood pressure was shifted toward higher values (> 175 mmHg), the maximum value of carotid compliance was observed for pressure levels close to 125 mmHg. This dissociation was more pronounced in older SHR (mean blood pressure 200 mmHg; maximum compliance 75 mmHg). CONCLUSIONS: The acute administration of vasodilators or of potassium cyanide induces relaxation of vascular smooth muscle and increases compliance for distension pressures of up to 125 mmHg. Since the drugs had no effects on arterial compliance at higher pressure levels, we conclude that in SHR acute vasorelaxation can increase operating compliance only if blood pressure is reduced. In contrast, chronic treatment with vasodilating agents is able to increase compliance even for higher blood pressure levels. Therefore, we suggest that chronic treatment can improve the elastic properties of the arterial wall through changes in the arterial wall structure. PMID- 1432315 TI - Sodium, large arteries and diuretic compounds in hypertension. AB - BACKGROUND: Clinical and experimental data have shown that different antihypertensive drugs do not cause similar changes in arterial compliance for an equipotent blood pressure reduction. There are no clear data on the effects of sodium and diuretics on the visco-elastic properties of the hypertensive arterial wall. DATA ANALYSIS: Cross-sectional epidemiological studies suggest that for given values of age and blood pressure, pulse wave velocity is lower in the presence than in the absence of a low sodium intake. Longitudinal studies indicate that in hypertensive subjects, a low sodium intake is associated with a larger brachial artery diameter than that seen with a high sodium intake. In hypertension in the elderly and in severe hypertension with end-stage renal disease, a sodium overload reduces arterial compliance and distensibility independently of blood pressure changes. In animal studies, the diuretic compounds cycletanine and indapamide increase systemic and carotid compliance independently of blood pressure changes. In contrast, in a crossover study in hypertensive subjects, the diuretic agent hydrochlorothiazide did not change arterial compliance and pulse wave velocity while the calcium entry-blocker felodipine did improve these hemodynamic parameters. CONCLUSION: The studies reviewed indicate that sodium may act on the arterial wall independently of blood pressure changes. the contribution made by counter-regulatory mechanisms, which may be related to the renin-angiotensin and the sympathetic nervous systems, might explain the differences between the clinical and the experimental changes observed with diuretic compounds. PMID- 1432316 TI - Drug-induced changes in mechanics and structure of cerebral arterioles. AB - BACKGROUND: Cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) undergo remodeling with a reduction in external diameter, paradoxically becoming more distensible, despite hypertrophy of the vessel wall. HYPOTHESIS: Two concepts have been proposed. (1) Remodeling of cerebral arterioles is an important mechanism, in addition to hypertrophy, of encroachment on the vascular lumen in SHRSP. (2) Increases in arteriolar distensibility partly compensate cerebral arterioles for other factors, such as hypertrophy and remodeling, which reduce the dilator capacity of these arterioles in chronic hypertension. EVIDENCE: Recently, we have studied the effects of reducing blood pressure by drug treatment or carotid clipping on hypertrophy and remodeling of cerebral arterioles in SHRSP. Our findings suggest that (1) pulse pressure may be a more important stimulus than mean pressure for hypertrophy of cerebral blood vessels and (2) remodeling of cerebral arterioles may occur independently of hypertrophy. CONCLUSION: Treatment that effectively prevents vascular hypertrophy during chronic hypertension may not be effective in preventing remodeling, and may therefore fail to restore cerebral vascular function to normal. PMID- 1432317 TI - Cardiac and vascular effects of chronic angiotensin converting enzyme inhibition at subantihypertensive doses. AB - AIM: We performed two sets of experiments in order to prevent or to regress cardiac and vascular hypertrophy, using antihypertensive and subantihypertensive doses of the angiotensin converting enzyme inhibitor zabicipril. METHODS AND RESULTS: Spontaneously hypertensive rats (SHR) begin to develop hypertension at less than 4 weeks of age and reach stable hypertension levels after 12-14 weeks. The blood pressure increase is accompanied by the development of cardiac and vascular hypertrophy. Treatment of SHR in utero and up to the age of 20 weeks with an antihypertensive dose of zabicipril (1 mg/kg per day) not only prevented the development of high blood pressure but also the development of cardiac and vascular hypertrophy. This effect was demonstrated by a significant decrease in left ventricular weight and the number of smooth muscle cell layers in the vascular media, media thickness and the media:lumen ratio in mesenteric arteries. In contrast, antihypertensive treatment with the Ca2+ antagonist verapamil (100 mg/kg per day) and the subantihypertensive dose of zabicipril (0.01 mg/kg per day) did not affect the development of cardiac and vascular hypertrophy. We found a significant increase in the length and surface density of myocardial capillaries after treatment with zabicipril at 1 mg/kg per day, indicating that the capillary density had improved and therefore that the oxygen supply of the heart was improved. Similar findings were observed with the low dose of zabicipril in SHR, although these rats had high blood pressure and cardiac and vascular hypertrophy. CONCLUSIONS: Treatment of adult SHR for 16 weeks with zabicipril at 1 mg/kg per day completely normalized their blood pressure levels. This effect was accompanied by a regression of left ventricular but not of vascular hypertrophy. Treatment with an antihypertensive dose of verapamil or with a subantihypertensive dose of zabicipril had no effect on cardiac and vascular hypertrophy. PMID- 1432318 TI - Clinical relevance of distal arterial compliance. AB - AIM: To calculate the compliance of resistance vessels. METHODS: Pressure-flow data (plethysmographic and sphygmomanometric) were obtained non-invasively from six normal and six hypertensive subjects, and the results were compared with similar data obtained previously from large blood vessels. The parameter used to represent compliance was extensibility (E), defined as the percentage change in radius for a given change in pressure. RESULTS: The hand vessels of hypertensive subjects (E = 0.126 +/- 0.034/mmHg) were significantly stiffer (P < 0.02) than those of the normotensive subjects (E = 0.272 +/- 0.047/mmHg); and the values of E for the resistance vessels were larger than those for the large arteries. PMID- 1432319 TI - Assessment of the arterial distension waveform using Doppler signal processing. AB - AIM: To determine the distension waveform of an artery. METHODS: Ultrasound signals returned by moving structures were processed by pulsed Doppler in order to detect the displacement of the signals with respect to the transducer as a continuous function of time. The results of two sample volumes combined, one located at the anterior and the other at the posterior wall of an artery, yielded the distension waveform of the artery. The distance between the sample volumes in combination with the distension from diastole to systole provided the local distensibility and compliance coefficients. To prevent any part of the structure under observation from moving outside the sample volume, the position of the sample volume was adjusted according to the displacement detected. A disadvantage with this method is that the phase interference of closely spaced structures, i.e. layers of the arterial wall, and the readjustment of the sample volume position may cause artifacts but these can be effectively suppressed by proper processing. CONCLUSIONS: The phase delay between two distension waveforms assessed simultaneously at a known distance can provide the local pulse wave velocity. Subsequently, the Moens-Korteweg relationship, expressing the relationship between pulse wave velocity and the distensibility coefficient, can be used to estimate the distensibility coefficient without measuring the local pulse pressure. The techniques, however, need further evaluation. PMID- 1432320 TI - Non-invasive method for the assessment of non-linear elastic properties and stress of forearm arteries in vivo. AB - AIM: To propose a method for obtaining non-invasive highly accurate measurements of arterial diameter, thickness and pressure at a single location on a peripheral arm artery, and use this data to estimate the status of the arterial wall. METHODS: Diameter and thickness were measured with an A-mode ultrasonic echo tracking device, with a precision of close to 1 micron. Pressure was measured with a photoplethysmograph at the finger level. A simple hemodynamic model was used to estimate, from the measured pressure pulse, the pressure waveform at the diameter-measuring site. RESULTS: The collected data made it possible to assess (1) the elastic response of the artery, through the compliance and distensibility, (2) the loading conditions, through the average stress-diameter curve and (3) the elastic properties of the wall material, through the incremental modulus of elasticity. CONCLUSION: This information can be used to assess the overall status of the arterial wall. PMID- 1432321 TI - In vitro assessment of diameter-pressure relationship in carotid arteries from normotensive and spontaneously hypertensive rats. AB - OBJECTIVE: To compare the mechanical properties of carotid arteries from normotensive and spontaneously hypertensive rats. DESIGN: The pressure-diameter relationships of carotid arteries from nine normotensive adult Wistar-Kyoto (WKY) and nine spontaneously hypertensive rats (SHR) were measured in vitro under control conditions and after poisoning the smooth muscle cells with potassium cyanide. METHODS: Changes in diameter due to changes in transmural pressure were determined with an ultrasonic dimensiometer (12 MHz). The diameter values were determined from the transit times of the pair of echoes given by the proximal and distal walls. The carotid artery was submitted to stepwise increases in pressure of 25 mmHg, from 0 to 200 mmHg; each pressure level was maintained for 5 min before the arterial diameter was recorded. RESULTS: The carotid artery pressure diameter relationship was a sigmoid curve in both strains. At the same level of pressure, the diameter of the carotid artery from SHR was significantly larger than that from normotensive rats (P < 0.05). Furthermore, the diameter values measured at the operating mean arterial pressure (roughly 100 mmHg for WKY rats and 150 mmHg for SHR) were markedly different (P < 0.001). In both strains, the diameter under passive conditions (with potassium cyanide) was significantly larger than that measured under control conditions (P < 0.01). CONCLUSIONS: Carotid arteries from SHR were significantly stiffer than those from WKY rats. Due to the pressure-dependency of the arterial wall stiffness, the increased arterial stiffness reported in hypertensive rats in vivo is related to an increase in distending arterial pressure and also to a significant reduction in the intrinsic compliance of the arterial wall. PMID- 1432322 TI - Introduction to arterial compliance and function. PMID- 1432323 TI - Inhomogeneities in arterial wall properties under normal and pathological conditions. AB - AIM: To determine whether there are inhomogeneities in arterial wall distensibility with age and hypertension. BACKGROUND: It has been known for some years that arteries lose their elasticity with increasing age and that they are less distensible in subjects with established and borderline hypertension than in age-matched controls. RESULTS OF DATA ANALYSIS: In the carotid artery changes in arterial wall properties are not homogeneously distributed along the bifurcation. Both in older subjects and in those with borderline hypertension the loss of distensibility is most pronounced in the carotid artery bulb, while in borderline hypertensives the proximal part of the bulb, where the baroreceptors are predominantly located, is more affected than other parts of the bulb. The loss of distensibility in the bulb may explain the diminished baroreceptor sensitivity observed in older subjects. The pronounced involvement of the proximal part of the bulb in the decreased distensibility in borderline hypertensives suggests that local stiffening, probably leading to disturbed baroreceptor sensitivity, may contribute to the development of hypertension in these patients. The pattern of inhomogeneities in wall distensibility in borderline hypertensives at a relatively young age (average 38 years) is similar to that seen in older normotensive subjects (average age 57 years), supporting the idea that arteries age faster in hypertensives than in normotensives. CONCLUSION: In management of the borderline hypertensive patient, consideration should be given to preventing early ageing of the arterial wall rather than following arterial blood pressure. PMID- 1432324 TI - Variability in arterial diameter and compliance: compliance modulation reserve. AB - BACKGROUND: Some antihypertensive drugs are known to increase arterial compliance in hypertensives; how far compliance can be increased is unknown. DESIGN: We studied eight mildly hypertensive patients to determine how far radial artery compliance can be acutely increased, i.e. the extent of the compliance modulation reserve. METHODS: We evaluated radial artery compliance by a new technique, assessing it throughout the cardiac cycle before and after the intra-arterial infusion of a vasodilator agent (papaverine). RESULTS: Before papaverine, compliance decreased progressively through diastolic to systolic blood pressure values. This was the case also during the papaverine infusion. However, over the full systolo-diastolic pressure range, compliance was increased by about 40% with papaverine. CONCLUSIONS: In hypertensive subjects radial artery compliance can be markedly increased on a acute basis, indicating that those antihypertensive drugs that improve compliance have a considerable reserve to act upon. PMID- 1432325 TI - Relationship between low-frequency oscillations of blood pressure and changes in arterial diameter. AB - AIM: To study spontaneous variations in radial artery compliance. METHODS: Compliance was evaluated non-invasively by an echo-tracking system, and variations in sympathovagal tone were analysed by a spectral analysis of continuous blood pressure recordings using a Fast Fourier algorithm. We studied 23 healthy volunteers, aged 25 +/- 4 years (mean +/- SD), at rest, on two occasions at least one day apart (5 +/- 3 days). RESULTS: There were no significant differences between the means of the arterial compliance measurements and those of the corresponding spectral analysis. However, the magnitude of change in the low-frequency periods (4-66 mHz) was significantly related (P less than 0.01) to a significant and inverse change in compliance for the same level of blood pressure. CONCLUSIONS: While it is possible to use spectral analysis to measure the effect of autonomic nervous regulation on radial artery properties, low-frequency periods cannot be safely ascribed to sympathetic effects alone. Other effects must also be taken into account in measurements of radial artery distensibility. PMID- 1432326 TI - Effects of diurnal variability and exercise training on properties of large arteries. AB - OBJECTIVE: To examine the diurnal variability in arterial distensibility and compliance and to study the effects of exercise training on these large artery properties. DESIGN: Vessel wall properties of the elastic common carotid and muscular brachial arteries were measured non-invasively with a vessel wall movement detector system in 12 healthy volunteers. Properties of the common carotid, the femoral and the brachial arteries were studied in 15 sedentary males in comparison with 15 male cyclists. RESULTS: Diurnal changes in the carotid and brachial arteries were similar. Blood pressure decreased at night while arterial diameter increased. Distensibility decreased and compliance was preserved at night. The vessel wall properties of the carotid artery did not differ between the sedentary males and the cyclists, but the femoral and brachial arteries were more elastic in the cyclists. The diameter of the femoral artery was larger in the cyclists. CONCLUSIONS: We found a diurnal pattern in changes in diameter and distensibility of elastic and muscular large arteries. Compliance, the buffering capacity of larger arteries, was preserved at night. The supplying femoral artery was larger and more distensible in cyclists. Exercise training did not affect the elastic carotid artery, but improved vessel wall properties of the brachial, and maybe also of other, muscular large arteries. PMID- 1432327 TI - Changes in arterial compliance induced by physical training in hammer-throwers. AB - OBJECTIVE: Physical training induces multiple changes in the cardiovascular system which allow an increased performance along with increased oxygen consumption. The present study was designed to investigate whether the changes include an increase in arterial compliance. METHODS AND DESIGN: In six normotensive right-handed hammer-throwers (aged 21.3 +/- 1.8 years, mean +/- SE) we measured radial artery diameter continuously via a new non-invasive echo tracking device, and beat-to-beat blood pressure. Arterial compliance was calculated by an arctangent model. In each subject measurements were made from both the left and the right arm. The data were compared with those obtained in six age-matched normotensive controls. RESULTS: Compared to the controls, the hammer-throwers had similar blood pressure, a lower heart rate and plasma norepinephrine and a higher left ventricular mass index and radial artery diameter. In the athletes, right radial artery compliance was significantly greater than either right or left radial artery compliance in the sedentary subjects (+61 and 63%, P < 0.05). It was also significantly greater than contralateral radial artery compliance (+53 +/- 8%, P < 0.05). CONCLUSIONS: Physical training is accompanied by an increase in arterial compliance. In our hammer-throwers this increase was mainly evident in the more highly trained arm, suggesting that local mechanisms are involved in this phenomenon. PMID- 1432328 TI - Effect of mental stress on the tone of a medium-sized muscular artery. AB - AIM: We studied the effects of mental stress on the tone of the radial artery, a medium-sized muscular artery. METHODS: Using an A-mode echo-tracking device coupled to a photoplethysmograph, we took continuous measurements of the radial artery diameter, heart rate and finger arterial pressure in six healthy young volunteers. RESULTS: Under mental stress, the heart rate increased from 63 +/- 4 to 74 +/- 4 beats/min (mean +/- SEM, P < 0.01) and systolic pressure from 123 +/- 5 to 140 +/- 6 mmHg (P < 0.05). No consistent modification in the arterial diameter was observed at this time. CONCLUSION: The activation of sympathetic nerve activity induced by mental stress does not cause a significant contraction in the radial artery. PMID- 1432329 TI - Abnormalities of vascular compliance in hypertension, aging and heart failure. AB - AIM: Diastolic arterial pulse wave analysis and a modified Windkessel model were used to evaluate the vascular response to hypertension, heart failure and aging. RESULTS: Compared to age-matched normal subjects, arterial compliance was reduced in patients with hypertension and heart failure, particularly in the vessels that contribute to resonances or oscillations in the pulse wave. In elderly subjects, the capacitive function of the arteries and compliance of the smaller arteries that contribute to oscillations were both reduced. CONCLUSION: These small-vessel structural or functional abnormalities may serve as a marker for disease and for the response to therapy. PMID- 1432331 TI - Estimating the elastic modulus of non-atherosclerotic elastic arteries. AB - BACKGROUND: Non-invasive measurements of the diameter and wall thickness of arteries in vivo, combined with recordings of pressure, permit the assessment of some mechanical aspects of arteries in vivo. However, arteries are anisotropic cylinders with complex elastic properties which can only be determined by a detailed evaluation. Many of the parameters required to calculate the anisotropic circumferential elastic modulus cannot be obtained in patients in vivo, or can be obtained only with difficulty. AIMS: Experiments were performed to assess the true anisotropic circumferential elastic modulus, and to find simpler methods of estimation. METHODS: One hundred and twenty dog carotid arteries were mounted in vitro and were extended to four lengths, 120, 130, 160 and 180% of the retracted length. The different lengths were applied in random order. The vessels were pressurized in steps while the longitudinal force and vessel diameter were measured. When a reproducible mechanical behavior was observed, the pressure, diameter and longitudinal force were recorded. These values were used to calculate the longitudinal elastic modulus, the circumferential-longitudinal Poisson's ratio and the true anisotropic circumferential elastic modulus with respect to the dimensions of the fully unloaded vessel. A number of simpler expressions were then evaluated for their value as approximations of the true anisotropic modulus. RESULTS: Excellent estimates were obtained with a variety of expressions. CONCLUSIONS: These methods may be useful for non-invasive assessments of the elastic properties of non-atherosclerotic arteries in patients. PMID- 1432330 TI - Arterial dilatory reserve in congestive heart failure. AB - AIM: The purpose of this study was to determine whether there are abnormalities in flow-mediated large vessel relaxation in patients with congestive heart failure (CHF). METHODS: The radial arterial diameter and flow responses upon the release of 10 min of forearm arterial occlusion (reactive hyperemia) were measured with ultrasound and Doppler devices. RESULTS: In patients with CHF there was a 26% reduction in peak blood flow (P = 0.09) compared to age-matched controls. However, the increase in arterial diameter that followed the peak blood flow was reduced by 49% in CHF (P < 0.01). CONCLUSIONS: The causes of the abnormal flow-mediated large artery relaxation in CHF are unclear; both structural and endothelial abnormalities may contribute. PMID- 1432332 TI - Introduction to wave reflection, wave travel and changes with modification of geometric and physical parameters. PMID- 1432333 TI - Determinants of isolated systolic hypertension in the elderly. AB - AIM: To study the determinants (or mechanisms) of isolated systolic hypertension in the elderly. METHODS: Pulsatile blood pressure and flow (multisensor catheter) were measured in the ascending aorta and impedance spectra were calculated in 18 subjects undergoing cardiac catheterization. Nine subjects (mean +/- SEM age 58 +/- 1.4 years) had increased aortic systolic (166 +/- 2.3 mmHg, P < 0.001), mean (116 +/- 2.1 mmHg, P < 0.02) and pulse blood pressure (83 +/- 2.1 mmHg, P < 0.001) and normal diastolic blood pressure (84 +/- 2.0 mmHg, NS) and constituted the isolated systolic hypertension group. The other nine age-matched (58 +/- 1.1 years) subjects had normal aortic systolic and diastolic blood pressure and constituted the normotensive control group. RESULTS: Both static (peripheral vascular resistance) and dynamic (characteristic impedance and wave reflection) components of left ventricular external load (aortic input impedance) were elevated in the isolated systolic hypertensives compared to the normotensive subjects; peripheral vascular resistance was 44% higher (P < 0.001), characteristic impedance (index of aortic stiffness) was 107% higher (P < 0.001), the first harmonic of impedance moduli (index of wave reflection) was 57% higher (P < 0.004) and the first impedance moduli minimum was shifted to a higher frequency (from 3.4 +/- 0.2 Hz to 4.2 +/- 0.13 Hz, P < 0.008) in the group with isolated systolic hypertension. CONCLUSIONS: The changes in impedance spectra in the isolated systolic hypertensives indicate that the cross-sectional area of the peripheral vascular bed was reduced and that the aorta and large arteries were stiffer, producing an increased pulse wave velocity and an early return of pulse wave reflection in systole. The marked increase in arterial stiffness in isolated systolic hypertension offset the increase in diastolic blood pressure that would have been expected from an increase in peripheral vascular resistance alone, and early return of the reflected pressure wave augmented aortic pressure throughout systole and accounted for the large increase observed in systolic and pulse pressure in the aorta. PMID- 1432334 TI - Arterial compliance and distensibility in spontaneously hypertensive rats. AB - AIM: These studies were undertaken in intact spontaneously hypertensive rats (SHR) to assess whether the elastic behavior of conduit arteries changes as a function of age. METHODS: We studied 16-week-old (n = 10) and 36-week-old (n = 10) SHR under fluothane anesthesia. Diameter-, compliance-, and distensibility pressure curves were established non-invasively for the carotid artery by means of a high-precision ultrasonic echo-tracking device. Intra-arterial pressure was monitored simultaneously in the contralateral carotid artery. RESULTS: Mean blood pressure was 197 +/- 6 and 185 +/- 3 mmHg (mean +/- SEM) in the younger and older SHR, respectively. No significant difference was observed between the two groups of rats in the diameter-, compliance- and distensibility-pressure curves. CONCLUSIONS: These results suggest that the elastic behavior of elastic arteries is not necessarily altered with aging in rats with genetic hypertension. PMID- 1432335 TI - Ageing and wave reflection. AB - AIM: To determine the effects of wave reflection on the increase in arterial pressure that occurs with age and its association with concomitant changes in both the magnitude and contour of the arterial pressure pulse. RESULTS OF DATA SURVEY: While age-related changes in mean pressure are similar in central and peripheral arteries, changes in pulse pressure and pulse waveform features are different. Because of the specific architectural, geometrical and elastic properties of the arterial vasculature, wave reflection plays an important role in determining peak pressure, the value usually specified as systolic pressure. While the late systolic increase usually determines peak systolic pressure in the central aorta, it is not necessarily related to the peak pressure in the periphery. Peak pressure depends on the timing and intensity of wave reflection, which is a function of the state of the peripheral microvasculature and the elastic properties of the large conduit arteries. Ageing causes changes in both the terminal and central vasculature, so that the intensity of the wave reflection and the transmission properties of arteries affect the arterial pulse to different degrees. Therefore, age-related changes that are observed in the central pressure pulse are different from those observed in the pulse when measured in a limb. Thus the contribution of wave reflection to the determination of peak arterial pressure is not the same at all locations. CONCLUSIONS: These findings have profound implications for therapeutic strategies aimed at altering systolic pressure and for a proper assessment of the alteration in cardiac load that occurs with age or with antihypertensive therapy, when measurements are taken in a limb. PMID- 1432336 TI - Opposing effects of ageing on distal and proximal large arteries in hypertensives. AB - AIM: Hypertension has been reported to accelerate the alterations in large arteries induced by ageing. Distal large arteries have been poorly investigated in contrast to proximal large arteries. The objectives of this cross-sectional study were (1) to compare the storage capacity of different arterial sites in normotensive subjects or hypertensive patients; and (2) to compare the different arterial sites with respect to the effects of ageing on storage capacity, in normotensives and in hypertensives. METHODS: Two recently developed ultrasonic echo-tracking devices, offering a high resolution for the assessment of internal arterial diameter and its systolo-diastolic variations, were used to measure end diastolic diameter, absolute (change at end-systole minus change at end-diastole) and relative (absolute change divided by change at end-diastole) changes in diameter with stroke and the absolute change in cross-sectional area (3.14 x the end-diastolic diameter x half the absolute stroke change in diameter) at the site of the common carotid artery, the abdominal aorta, the common femoral artery, the brachial artery and the radial artery in 50 untreated essential hypertensive patients and 32 normotensive subjects. RESULTS: In both groups, the end-diastolic diameter increased with age for the common carotid artery and the abdominal aorta but not for the common femoral, brachial or radial arteries. In the normotensives, the relative stroke change in diameter was negatively correlated with age for the common carotid artery (P < 0.001) and the abdominal aorta (P < 0.001), and not correlated for the common femoral, brachial and radial arteries. In hypertensives, the relative stroke change in diameter was negatively correlated with age for the common carotid artery (P < 0.05) and the abdominal aorta (P < 0.05), positively correlated with age for the common femoral (P < 0.05) and the radial arteries (P < 0.05) and not correlated for the brachial artery. Similar results were observed for the relationships between the absolute change in cross-sectional area and age. CONCLUSIONS: In hypertensives, enlargement of the proximal large arteries offsets the decrease in the relative stroke change in diameter and maintains an adequate storage capacity. It thus appears that ageing exerts opposing effects on central elastic large arteries and distal muscular medium-sized arteries. PMID- 1432337 TI - Body height as a determinant of carotid pulse contour in humans. AB - AIM: The aim of this study was to assess the effect of body height on arterial wave reflections and the carotid pulse pressure contour in humans. METHODS: In 85 men, the carotid pulse wave and arterial wave reflections were determined from the common carotid artery pulse contour as recorded by applanation tonometry using a Millar micromanometer-tipped probe. The arterial wave reflection was calculated as the ratio of the height of the late systolic peak to the total height of the carotid pulse wave. The reflected wave was timed from the foot of the pressure wave to the foot of the late systolic peak. RESULTS: Multiple regression analysis showed that body height and aortic pulse wave velocity were the principal determinants of travel time of the reflected wave and of arterial wave reflections (P < 0.0001), short stature being associated with a short travel time and increased reflections (P < 0.0001). CONCLUSIONS: Body height is a determinant of arterial wave reflections and peak systolic blood pressure in humans. PMID- 1432338 TI - Pharmacological potential for reversing the ill effects of ageing and of arterial hypertension on central aortic systolic pressure. AB - CARDIOVASCULAR RISK: Systolic arterial pressure is an important risk factor for future cardiovascular morbidity and mortality. PULSATILE LOAD: The aortic systolic pressure with which the heart interacts is determined by pulsatile vascular load. In particular, wave reflections from peripheral sites affect peak central aortic systolic pressure but not brachial systolic pressure. DRUG POTENTIAL: Drugs that reduce wave reflection and hence reduce the pulsatile vascular load in addition to reducing peripheral resistance have the potential to reduce target organ damage to a greater extent than drugs that reduce mean pressure and resistance alone. PMID- 1432339 TI - Contrast detection in luminance and chromatic noise. AB - We measured detection thresholds for a vertically oriented 1.2-cycle-per-degree sine-wave grating embedded in spatiotemporal broadband noise. Noise and signal were modulated in different directions in color space around an equal-energy white point. When signal and noise were modulated in the same direction, we observed a linear relationship between noise spectral density and signal energy at threshold. The slope of this function was the same whether the modulation was along a luminance axis or a red-green axis. If the signal was on one axis and the noise was on the other, no masking was observed. These results support the notion of two independent and equally efficient mechanisms tuned to these directions. We then measured threshold elevations for masks with both chromatic and luminance components. When signal and noise were modulated along the same line (for example, bright red and dark green), thresholds were elevated. When we inverted the phase of the chromatic component of the noise relative to the luminance component (bright green and dark red), the masking effect disappeared, even though the amount of noise in the putative luminance and chromatic mechanisms was exactly the same as before. This implies that detection performance is limited by mechanisms sensitive to both luminance and chromatic contrast signals. We characterized these mechanisms by their spectral tuning curves. PMID- 1432340 TI - Analysis of visual modulation sensitivity. V. Faster visual response for G- than for R-cone pathway? AB - To determine the linear, unadapted responses of the cone pathways, we have measured the critical fusion frequency (CFF) for green (555-nm) and red (642-nm) flicker as a function of retinal illuminance. Both functions obeyed the Ferry Porter law (CFF proportional to log illuminance) to high accuracy over a > or = 5 log-unit range. In both foveola and periphery the CFF/illuminance functions were significantly steeper for green light than for red light. The peripheral 555-nm function had an average slope 1.26 times the average slope of the 642-nm function. An additive model of flicker detection could not account for the observed differences in slope. A threshold independence model, in which detection is based on the most sensitive mechanism, accurately fits the data. Whichever model is assumed, the presence of different slopes for the two wavelength flicker conditions strongly implies that the R- and G-cone pathways have different temporal properties. The occurrence of steeper CFF/illuminance slopes in response to green light implies that the linear (near-CFF) response of the G-cone pathways in inherently faster than that of the R-cone pathways at both retinal loci. These differences in R- and G-cone-mediated temporal properties complicate the fundamental concept of luminance and invalidate it for precise application over the full illuminance range. PMID- 1432341 TI - Linear models of surface and illuminant spectra. AB - We describe procedures for creating efficient spectral representations for color. The representations generalize conventional tristimulus representations, which are based on the peripheral encoding by the human eye. We use low-dimensional linear models to approximate the spectral properties of surfaces and illuminants with respect to a collection of sensing devices. We choose the linear-model basis functions by minimizing the error in approximating sensor responses for collections of surfaces and illuminants. These linear models offer some conceptual simplifications for applications such as printer calibration; they also perform substantially better than principal-components approximations for computer-graphics applications. PMID- 1432342 TI - Enamel management during orthodontic treatment. PMID- 1432344 TI - A manpower study of orthodontic specialists for the State of Indiana: a preliminary report. AB - To develop current manpower data and project the future need for orthodontic specialists, a survey questionnaire was mailed to Indiana orthodontists (90 percent response). In addition, a telephone survey of orthodontic receptionists was conducted during the same time period (95 percent response). In general, orthodontists perceived a lower state of business than did their staffs. About 77 orthodontists are expected to retire by the year 2010. Based on maintaining the adjusted potential patient-to-orthodontist ratio (increasing adult and declining children in the population), it was projected that only about 66 (86 percent) of the retirees require replacement. To maintain manpower at eight percent fewer orthodontists than are currently in practice, three to four new orthodontists per year will be needed in Indiana over the next two decades. PMID- 1432343 TI - Orthodontic decalcification management with microabrasion. AB - Patient home care during orthodontic treatment is often less than ideal. For those patients who routinely let plaque accumulate around orthodontic appliances, there can be white or stained areas of decalcification around the bonded appliances. Management of this esthetic problem can be accomplished in several ways depending on the severity of the defect. This paper describes the very conservative technique of microabrasion which works well in removing superficial markings caused by decalcification. In a sample of 98 decalcified teeth from 20 patients with orthodontic decalcifications and various other unesthetic stains, microabrasion removed most or all of the disfiguring marks on 78.5 percent of the teeth evaluated. At least some improvement was noted 96.9 percent of the time. These results were statistically significant (P > .01). It seems appropriate to employ this technique prior to initiating more aggressive cosmetic dentistry such as resin bonding, Class V restorations, or labial veneers. PMID- 1432345 TI - One hundred years of orthodontics. PMID- 1432346 TI - Control of orthodontic pain. AB - Orthodontics is an elective dental procedure generally believed to involve pain. In certain individuals, the pain caused by orthodontic tooth movement can be a major negative component of the entire therapy. Clinicians who are aware of this fact can attempt to prevent pain rather than ameliorate it once it is present and help make the experience a more positive one for the patient. Orthodontic forces should be kept at suitable levels and care taken to prevent trauma due to hyperocclusion. In procedures suspected to cause significant painful stimuli (such as forcing bands on unseparated teeth, removal of fixed expanders, initial placement of archwires, or lingual arches), or in particularly sensitive patients, the use of analgesics may be indicated. These agents should be taken prior to the procedure and for a minimum of 24 hours following the procedure. Acetaminophen is recommended in young children, while nonsteroidal anti inflammatory agents are indicated in older patients. PMID- 1432347 TI - Influence of lower lip support on recording of vertical dimension in edentulous patients. AB - The purpose of this investigation was to assess the influence of differences in design of the occlusion rim on recorded vertical dimension in complete denture therapy. Edentulous patients were studied with an opto-electronic method when the vertical dimension of rest was established with and without labial support of the occlusion rim. As no significant differences were found, the results did not support the hypothesis that the contour of the lip support will influence the recorded physiological rest position. However, a significant difference between intra and extraoral placement of the point of measurement was found. PMID- 1432348 TI - Influence of porcelain material and composite luting resin on microleakage of porcelain laminate veneers. AB - The microleakage beneath porcelain laminate veneers was investigated. The restoration margins were located according to the preparations made below or above CEJ of extracted maxillary central incisors. Vitadur N and Microbond porcelain materials were used to prepare laminate veneers. A light cured composite resin (Porcelite) and a light- and chemical-cured composite resin (Porcelite Dual Cure) were used as luting agents. The bonded specimens were thermocycled and by employing the standard dye penetration technique, the leakage was scored from cervical and incisal margins. Significantly greater microleakage was recorded at the dentine composite resin interfaces than at the enamel/composite interfaces. Statistically insignificant differences were observed with the use of the four cement/porcelain combinations studied. PMID- 1432349 TI - Swallowing activity of lip muscles in patients with a complete upper and a partial lower denture. AB - In 30 partially edentulous subjects provided with an immediate complete upper and a partial lower free-end denture the lip activity in swallowing was studied before and after denture treatment and during a 2-year period of denture wearing. Electromyographic recordings of the right side upper and lower orbicularis oris, mentalis and anterior temporal muscles were obtained during swallowing saliva and during swallowing of water with and without the dentures in the mouth. In the different types of swallows recorded, the lower lip and mentalis muscles showed much stronger activity than the upper lip and anterior temporal muscles and also initiated the swallowing activity. No significant changes in mean voltages of the swallowing activity were observed during the 2-year observation period. On the other hand, the durations of the swallows showed marked increases after 1 year of denture use, when no further rebasings of the complete upper denture had been made. PMID- 1432350 TI - Effects of nickel-chrome dental alloys used in dentistry on saliva and serum nickel levels, peripheral T-lymphocytes and some other blood parameters. AB - Epidemiological investigations have shown that nickel is a potent sensitivity producing agent. However, it is not known if intra-oral use of nickel-chrome alloys can cause any sensitization reaction. The purpose of this study was to determine if nickel-chrome alloys used in dentistry influence nickel levels in saliva and serum and whether there were associated changes of some blood parameters such as lymphocyte, T-lymphocyte, neutrophil, eosinophil, basophil and monocyte. The study was performed on 10 patients all of whom had no medical and dental history of using nickel containing drugs or restorations. Four unit fixed partial prostheses containing 22.97% nickel and 22.65% chrome were constructed and worn by the patients. Blood and unstimulated whole saliva samples were taken from the patients before insertion of the prostheses and then 1 month and 6 months post-insertion. Hematocrit determinations, total and differential leucocyte count, total T-lymphocyte counts and serum nickel concentrations were determined from the blood samples and salivary nickel concentrations from the saliva samples. It was found that there were no significant changes in circulating T-lymphocyte and monocyte population but a decrease was found in circulating eosinophil and an increase in circulating neutrophil and basophil populations. PMID- 1432351 TI - Signs and symptoms of temporomandibular joint dysfunction in a Saudi Arabian population. AB - The signs and symptoms of temporomandibular joint dysfunction present in 219 Saudi Arabians attending a dental clinic for routine dental treatment are described. Joint sounds (36%) and muscle tenderness to palpation (34%) were common findings. Of the subjects examined, 31% reported suffering from frequent headaches. The study demonstrated a high incidence of signs and symptoms of temporomandibular joint dysfunction. Findings were similar to those of a previous study of an investigation in a bedouin community in Western Egypt (Abdel-Hakim, 1983). PMID- 1432352 TI - Analysis of a central maxillary incisor by using a three-dimensional finite element method. AB - An attempt is made for determining the stress distribution in a maxillary central incisor by using a three-dimensional finite element model. The tooth is assumed isotropic, homogeneous, elastic and unsymmetrical. A load of 450N, 26 degrees to the longitudinal axis is applied on the incisal margin of the tooth. The distribution of compressive, tensile and shear stresses were plotted for the whole tooth structure. It is found that cracks or fractures occur under the given load. PMID- 1432353 TI - Effect of metal strengthener's surface roughness on fracture resistance of acrylic denture base material. AB - The aim of this study was to clarify the effect of the surface roughness of various metal wires on the fracture resistance of the acrylic test specimens. The number of test groups compared were 16, and there were 30 test specimens in each group. The investigation showed that the surface roughening of the metal wires used to reinforce acrylic resin denture base material increased the fracture resistance of the test specimens. The best results were achieved by sandblasting. The differences in resistance were also statistically significant. PMID- 1432354 TI - The masticatory pattern as an adjunct for diagnosis and treatment. AB - The sagitally-viewed masticatory pattern was investigated in 125 dentate patients. In 25 patients, the phenomenon of an incisal guided phase during mastication was observed. Clinical examination of these cases revealed slight to severe incisal attrition or various degrees of flaring. The hypothesis that the incisal guided phase contributes to this phenomenon and should therefore be taken into consideration during treatment is put forward. PMID- 1432355 TI - Methodological observations on positive and negative work (teeth grinding) by human jaw muscles. AB - Through electrognathography and surface electromyography of the right and left masseter muscle (MM), this methodologic study examined the excentric (lengthening) and concentric (shortening) contractions of brief (2000 ms) voluntary teeth grinding performed through canine as well as group function of the opposing teeth. We inferred that the most anterior and superior portions of the right and left MM were lengthened and shortened by at least 4.23 mm (right MM) and 4.82 mm (left MM). For the negative work efforts (excentric contractions) of canine function, the tensions of the ipsilateral MM ranged from 10 to 20% MVC and those of the contralateral MM from 4 to 14% MVC. For the positive work efforts (concentric contractions) of canine function, the tensions of the ipsilateral MM ranged from 11 to 44% MVC and those of the contralateral MM from 20 to 41% MVC. A comparison between canine and group function showed that the negative as well as positive work efforts of group function exceeded those of canine function. PMID- 1432356 TI - A comparative study of two methods for the orientation of the occlusal plane and the determination of the vertical dimension of occlusion in edentulous patients. AB - The aim of this study was to compare two methods used to orientate the occlusal plane (OP) and to determine the vertical dimension of occlusion (VDO). In method A the VDO was established by means of the rest position, the minimal speaking distance, and the patient's profile. Method B used a newly developed registration pin assembly. The VDO was registered using a silicone occlusion rim and the swallowing technique. The results were compared to the values of the new dentures. Three standardized lateral radiographs were taken at the VDO obtained with methods A, B, and at that of the final dentures. On each radiograph the orientation of the OP to the Camper plane and the VDO were measured by two investigators independently. The results indicated no statistically significant differences between the mean VDO with method A and B compared with the new dentures (P greater than 0.05). With both methods it was not possible to orientate the OP parallel to the Camper plane. None of the occlusal planes of the new dentures were parallel either. Their OP diverged on average by 7 degrees dorso-caudally. The time spent with method B to orient the OP and to determine the VDO was significantly lower than with method A (17-50 min). PMID- 1432357 TI - Frequency analysis of electromyographic signals in mandibular elevators at maximum clench level. AB - Power spectral analysis of electromyogram (ENG) was used to investigate the relationship between mean power frequency (MPF) and sustained contraction time. Surface EMG activity was recorded from masseter and anterior temporal muscles on both sides for seven healthy subjects while clenching at intercuspal position in maximum potential level of these muscles. A visual sense feedback of EMG potential was used to control clenching level. According to linear regression analysis, there was a negative correlation between MPF of EMG and sustained contraction time. The results indicate that the slope of MPF versus contraction time may be used for detecting muscular fatigue in the stomatognathic system. PMID- 1432358 TI - Chemically humanized murine monoclonal antibody against a cell nuclear antigen: usefulness in autoimmune diagnostics. AB - The cellular nuclear antigen SS-B/La is known to be a major antigenic target to an autoantibody in patients with Sjogren's syndrome and systemic lupus erythematosus. It is useful to detect an anti-SS-B/La antibody from patients' sera in a clinical point of view. We purified SS-B/La from rabbit thymus acetone powder by affinity chromatography with a murine anti-SS-B/La monoclonal antibody (1C3-H7). An enzyme-linked immunosorbent assay method, in which SS-B/La was used to coat a plate, was also successfully established. It is difficult to obtain a large volume of patient's serum with high antibody titer and high specificity as a positive control. We investigated whether or not a positive control from human could be replaced by a murine monoclonal antibody to SS-B/La. The 1C3-H7 was conjugated with a human IgG Fc' fragment using N-gamma maleimidobutyryloxysuccinimide as a cross-linker. The chemically humanized murine monoclonal antibody (1C3-Fc') was recognized by antiserum specific for human IgG Fc fragment. 1C3-Fc' reacted to SS-B/La but not to other antigens. Furthermore, the titration curve of this conjugate ran parallel with those of patients' sera specific for SS-B/La. It is concluded that a chemically humanized murine monoclonal antibody is useful as a positive control in place of a human patient's serum. PMID- 1432359 TI - Simultaneous expression of type I procollagen mRNA and albumin in cirrhotic human liver. AB - The gene expression of human type I procollagen was investigated in cirrhotic human liver by using in situ hybridization with nonradioactive DNA probes. Using in situ hybridization can provide direct evidence for the cell type capable for type I collagen synthesis in tissues. T-T dimerized DNA probes were used and DNAs hybridized in situ were detected immunohistochemically using specific antibodies against T-T dimer. The data demonstrated that type I collagen is synthesized in hepatocytes and stellate cells in pseudolobules and in fibroblasts in Glissons capsules in cirrhotic human livers. We indicated hepatocytes morphologically and functionally by using immunohistochemical localization of albumin, which was used as a marker of hepatocyte, since albumin is synthesized exclusively by hepatocytes. PMID- 1432360 TI - Comparison of various methods for the enumeration of blood cells in urine. AB - This study compared the use of conventional urine microscopy, the KOVA system, Neubauer hemacytometry, and the Yellow IRIS for the determination of white blood cell (WBC) and red blood cell (RBC) counts in urine samples. Both KOVA WBC and RBC counts correlated better with the IRIS counts than with conventional microscopy. KOVA WBC counts correlated with Neubauer hemacytometry to the same degree as they did with IRIS WBC counts. The RBC count correlation was fairly similar between KOVA, hemacytometry, and the conventional method. It was concluded that the KOVA system is a suitable replacement for conventional urine microscopy. PMID- 1432361 TI - A homogeneous assay system of aspartate aminotransferase iso-enzymes using proteases and application for clinical evaluation of myocardial infarction. AB - We designed a rapid, homogeneous assay for human aspartate aminotransferase (AST) isoenzymes, by a selective proteolysis of soluble AST (s-AST), using chymotrypsin and protease 401. The linearity of mitochondrial (m-AST) was elongated up to 4000 U/l. m-AST values from the human liver, and determined by a homogeneous assay using protease 401 or chymotrypsin, were relative to those obtained using an immunoprecipitation method. In perioperative patients or those with an acute myocardial infarction, the peaks of s-AST and m-AST values were noted 13 h and at 57 h after ictus, respectively, whereas the peak of ratio between was seen 6 h after ictus. In the case of Budd-Chiari syndrome, the maximum levels of the two AST activities were evident 14 days after hospitalization and the peak of ratio between them was seen after 7 days. We propose that this homogeneous assay can serve as a diagnostic tool for early phase detection of myocardial infarction and of Budd-Chiari syndrome. PMID- 1432362 TI - Influence of biological variations and sample handling on measured microalbuminuria in diabetic patients. AB - Five immunochemical assays for determining low concentrations of albumin were investigated. These were a radioimmunoassay (RIA); turbidimetric immunoassays (TIA) both according to end-point measuring principle on a Cobas Fara and Hitachi 717 analysers, and according to kinetic measuring principle on a Turbitimer instrument; and a nephelometric immunoassay (NIA). All achieved the analytical goal necessary for optimal patient care. The correlations between the albumin concentrations measured with the different techniques were very good. In vitro glycation of albumin did not influence albumin concentrations measured by the five assays. Urine albumin excretion measured over 3 consecutive days showed considerable day-to-day variation. This was highest for spot-urine specimens and significantly lower for 24 h and timed-overnight samples. Variation of storage temperature (room temperature, 4 degrees C, -20 degrees C), time (up till 3 months), and pH (within the range pH 5-8) of the urine samples did not change significantly the measured albumin concentrations. Different sample preparations (vortex-mixing, centrifugation, and thawing) had no influence on the measured albumin concentration. In conclusion, a maximum standardization of the collection of timed-overnight urine samples for screening and 24 h urine samples for confirmation of microalbuminuria during 3 consecutive days is more crucial than the choice of the immunological technique. PMID- 1432363 TI - Enzyme immunoassay for specific analysis of pancreatic stone proteins in human pancreatic juice. AB - In order to study the concentration of pancreatic stone protein (PSP) in human pancreatic juice, we investigated the influence of the insoluble form of PSP-S1 converted from PSP-S2-5 on PSP determination and the assay method for PSP-S1 precipitate after solubilizing PSP-S1. When bovine trypsin was added to pancreatic juice, PSP-S1 was converted from PSP-S2-5 and precipitated about 45 85% after 1 h. The precipitated PSP-S1 was dissolved in 0.1 M sodium acetate buffer, pH 4.0, and the concentration was measured by the enzyme immunoassay, with similar reactivity to PSP-S1 and PSP-S2-5. The proposed method can offer accurate and specific analysis of the PSP level in pancreatic juice. The results of the fractionation of pancreatic juice and duodenal juice on Mono S cation exchange chromatography suggested that the major component of PSP was PSP-S2-5 in pancreatic juice and PSP-S1 in duodenal juice. PMID- 1432364 TI - Automated microparticle enzyme immunoassay for neural thread protein in cerebrospinal fluid from Alzheimer's disease patients. AB - An automated microparticle enzyme immunoassay (MEIA) with the IMx analyzer for the detection of neural thread protein (NTP) in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients was developed. This assay uses monoclonal antibodies produced against the purified pancreatic form of the protein. The assay employs one monoclonal antibody covalently coupled to the microparticle to capture immunoreactive material in CSF or brain tissue. The second monoclonal antibody was conjugated to alkaline phosphatase and serves as detection antibody. The assay provides results in approximately 45 minutes with a sensitivity of 60 pg/ml (3 fmoles/ml). The titration curve of both normal and AD CSF resulted in a linear relationship with respect to the volume of CSF used. A similar relationship was observed when normal and AD brain tissue extracts were serially diluted. The molecular weight of NTP in CSF was approximately 20 kD as determined by gel filtration method under non-denaturing conditions. The recovery for pancreatic thread protein (PTP) spiked in either normal or AD CSF was 104% and 108%, respectively. Intra-, inter-, and total assay CVs (coefficient of variation) for controls were less than 2.9%, 3.3% and 3.0%, respectively. This assay will provide a useful tool in the study of the Alzheimer's disease and may help research in diagnosis and prognosis of Alzheimer's disease and related disorders. PMID- 1432365 TI - A flexible, efficient, checkerboard immunoblot system for the detection and semiquantitation of specific antinuclear antibodies. AB - In this paper an uncomplicated method for the simultaneous detection and semiquantitation of 11 of the 12 commonly studied antinuclear antibodies (ANA) in a single run is described. This new application of checkerboard immunoblotting (CBIB) is based upon available technology and employs purified antigens which can be either purchased or produced in-house. CBIB requires no electronic instrument, can be formatted to meet the needs of the user, is rapidly performed, and has acceptable labor and materials costs. Data on the use of the method to examine available reference antisera is presented. CBIB has also proven practical for the clinical study of 18 sera, at two dilutions per membrane, for each set of specific antinuclear antibodies, also at two or more dilutions. PMID- 1432366 TI - Comparison of two automated nephelometers. AB - The intercalibration precision and linearity were determined for two representative analytes, apolipoprotein A1 (apo A1) and immunoglobulin G (IgG), on the Beckman Array and the Behring Nephelometer 100 (BN-100). For two of nine samples analyzed, poor precision was observed for IgG with the Array. The poor precision for these two samples is attributed to large systematic shifts. A statistical non-linearity was observed for apo A1 with the BN-100, but this non linearity does not exclude use of this assay for clinical diagnosis. Method comparisons were done for 12 analytes: apo A1, apo B, IgG, IgA, IgM, IgE, C3, C4, albumin, C-reactive protein, alpha-1-antitrypsin, and ceruloplasmin. These comparisons showed proportional biases of > 10% for seven of 12 analytes. Furthermore, correlation coefficients were < 0.96 for seven of 12 analytes. We conclude that comparing results obtained from the two different nephelometers is of only limited value for the individual patient. PMID- 1432367 TI - Streptomyces: a superior source for cholesterol oxidase used in serum cholesterol assay. AB - The present study compared three cholesterol oxidase sources (Nocardia, Streptomyces, and Pseudomonas sps.) for serum cholesterol assay. We found cholesterol oxidase isolated from Streptomyces was superior than those isolated from Nocardia and Pseudomonas sps. Performances of the reagent contained Streptomyces cholesterol oxidase was excellent and comparable to the performances obtained from reagent contained Nocardia cholesterol oxidase. Moreover, the reagent containing Streptomyces cholesterol oxidase had the lowest cost and had the longest shelf-life ($U.S. 0.17/mL, 10 weeks) compared to the reagent contained Nocardia ($U.S. 0.50/mL, 8 weeks) or Pseudomonas ($U.S. 0.20/mL, 6 weeks) cholesterol oxidase. PMID- 1432368 TI - Immunoelectron microscopic localization of antigens which react with islet cell cytoplasmic antibodies within human pancreatic beta cells. AB - The presence of circulating autoantibody to islet cell cytoplasm is considered to be an important marker of Type 1 (insulin-dependent) diabetes mellitus. In the present study using islet cell cytoplasmic antibody positive patient sera as the first antibody, we studied the intracellular distribution of its antigen at the electron microscopic level using the pre-embedding immunoperoxidase method. Specific immunoreactivity was found in the membranes of beta cell-secretory granules and cytoplasmic membranes. This result is compatible with the interpretation that the antigen(s) on the membranes of beta cell secretory granules is (are) the target of islet cell cytoplasmic antibody. PMID- 1432369 TI - Single point quantification of antibody by ELISA without need of a reference curve. AB - A new method for the quantification of antibodies in the enzyme-linked immunosorbent assay is described. This procedure replaces titer determinations based on end-point dilution of the antibody under investigation. Here, the sample is tested in a single dilution and the optical density (OD) obtained is used in the equation log10 titer = alpha.OD beta. The titer can then be calculated by inserting into the formula the values for the constants alpha and beta, which are specified by the manufacturer for each separate batch of kit reagents. This so called alpha-method saves time and reagents while providing results which are equal to the titration method in accuracy and superior in precision. The alpha method is also a simpler and reliable alternative to the use of standard or reference curves for the quantification of the antibodies in I.U./ml. PMID- 1432371 TI - Pathological Society of Great Britain and Ireland, 165th meeting. 9-11 July 1992. Abstracts. PMID- 1432370 TI - Clinical significance of soluble interleukin 2 receptor for monitoring the diseases associated with activated lymphocytes and viral infections. PMID- 1432372 TI - Application of quality of life measures in health care delivery. PMID- 1432374 TI - Quality of life. Special issue. PMID- 1432373 TI - Quality of life in developing countries. PMID- 1432375 TI - Health policy and the quality of life. PMID- 1432376 TI - Quality of life across age and family stage. AB - It is clear that the quality of life of the individual is intertwined with that of his or her family. Therefore, health care professionals and other professionals who work with families facing terminal illness must (1) identify those factors that put the patient and the family at risk of suffering further disruption of psychosocial quality of life and (2) seek out whatever resources are necessary to help the patient and the family improve their quality of life. Families with young children are more dependent on external resources than are other families, and they place more strains on the spouse caregiver. If these resources are not available, parents are less able to handle crucial developmental family matters. Clinicians who are aware of this deficit are better able to recognize role performance problems and help families obtain the external resources. Secondly, families who have relied on ascribed roles before the parent fell ill are at greater risk of psychosocial dysfunction: they lack appropriate ways to deal with role reallocation in order to make the best use of their talents. Professionals who are sensitive to this can help families adapt to role changes. A third area that places families at risk is poor spousal communication. Good communication patterns appear to facilitate adjustment to both terminal illness and bereavement (4,6). Professionals trained in family and social therapy are equipped to help family members develop effective communication, which can in turn help them prioritize tasks, seek outside resources when needed, and negotiate role assignments. PMID- 1432378 TI - Quality of life for families in the management of home care patients with advanced cancer. PMID- 1432377 TI - Quality of life: the family and Alzheimer's disease. AB - AD possesses unique features that make caregiving particularly burdensome. The quality of life of the caregiver is inevitably affected, but there are many intervening variables such as the strength of the existing relationship and the presence of a social support system that can mediate the outcome. Health professionals can play a vital role by providing a continuous source of advice, support, and help to assist the caregiver in the difficult task of tending a loved one during this long and stressful illness. PMID- 1432379 TI - Photoinduced cutaneous inflammatory response by psoralens. AB - Our studies describe the inflammatory response in rabbit skin induced by topical application of 8-methoxypsoralen (8-MOP) and UVA-visible irradiation (320-700 nm). Increase in vascular permeability (iVP) and accumulation of polymorphonuclear leucocytes (aPMN) at the test sites were quantitated using 125I albumin and 51Cr-labelled PMNs respectively. Erythema was graded visually. 8-MOP cream was applied topically and irradiated. The erythemal response, aPMN and iVP at the test sites were quantitated at 6, 24, 48 and 72 h post-irradiation. The iVP and aPMN were maximal at 24 h; the erythemal response was the same at 24-48 h. The responses were dependent on 8-MOP concentration and irradiation dose. Topical application of 200 micrograms 8-MOP cream followed by irradiation for 2 h (9.4 J cm-2) produced 3-7 times iVP, 2-4 times aPMN and intense erythema at the test sites after 24 h. Neither aPMN nor iVP was detected before 6 h and erythemal response was not observable up to 16 h after irradiation. The aPMN and iVP gradually subsided in 72 h, although the erythemal response was still present. The repeated exposure of 8-MOP-treated sites for three consecutive days 24 h apart did not produce appreciable iVP or aPMN at 72 h or 24 h after the last exposure; however, erythema persisted. The 8-MOP-treated sites previously exposed for three consecutive days on reapplication of 8-MOP cream plus irradiation showed significantly less response compared with non-pretreated sites. Our results suggest that the erythemal response is not directly related to either iVP or aPMN. PMID- 1432381 TI - Ultraweak photons emitted by cells: biophotons. PMID- 1432380 TI - Biological implications of aerobically obtained riboflavin-sensitized photoproducts of tryptophan. PMID- 1432382 TI - Synthesis of psoralens and analogues. AB - This review presents briefly the various classical syntheses of psoralens and angelicins which generally start from preformed suitably substituted coumarin or benzofuran derivatives. However, the discovery of the photocyclo-C-4 addition of psoralens to pyrimidine bases prompted new developments in this area. In particular, improved synthesis of psoralens and substituted angelicins, and synthesis of new analogues such as furochromenes, pyridopsoralens, pyrano benzopyrandiones, dioxinocoumarins and aza-psoralens were described recently. This review focuses on the chemical syntheses of these various compounds. PMID- 1432383 TI - The evolution of photochemotherapy with psoralens and UVA (PUVA): 2000 BC to 1992 AD. AB - The therapeutic uses of naturally occurring psoralens in modern-day medicine (8 methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 4,5',8-trimethylpsoralen, and a few other synthetic psoralens) have evolved through five stages of development. (1) In the historical period (2000 BC to 1930 AD), the pigment-stimulating properties of naturally occurring plants containing psoralens were described anecdotally. (2) The second period (1930-1960) dealing with the chemistry of psoralens involved extraction, identification of their structure, synthesis, and the relationship between chemical structure and their photoreactivity and pigment stimulating properties. The treatment of vitiligo with oral and topical 8-MOP became popular. (3) In the third period (1960-1974), we witnessed a new beginning and the growth of basic science studies and clinical investigations into various biological properties of psoralens including action spectrum studies, mutagenesis and carcinogenesis studies, in vitro and in vivo photoreactivity studies of various psoralens with DNA, RNA, proteins, and pharmacological and toxicological studies in vitiligo patients undergoing long-term therapy for repigmentation. (4) The fourth period (1974-1988) is recognized as the period of photochemotherapy and the development of the science of photomedicine which established the therapeutic effectiveness of psoralens in combination with newly developed UV irradiation systems that emitted high-intensity UVA radiation in the treatment of severe psoriasis, mycosis fungoides, and over 16 other skin diseases. The effectiveness of PUVA (psoralen + UVA) was confirmed by well controlled clinical trials in thousands of patients, both in the USA and in European countries. Combination therapy with oral retinoids and PUVA contributed to greater effectiveness and long-term safety of psoralen photochemotherapy. (5) In the fifth period (1989 and beyond), psoralens are now emerging as photochemoprotective agents against non-melanoma skin cancers and as immunologic modifiers in the management of certain patients with disorders of circulating T cells using new techniques of photopheresis. In the final analysis, perhaps the application of pharmacological and therapeutic concepts and principles of using psoralens in combination with UVA has contributed to the development of a new science of photomedicine in which the interaction between basic scientists, photobiologists, and physicians has produced both basic and new clinical knowledge for the care and control of human suffering. PMID- 1432384 TI - New aspects of the repair and genotoxicity of psoralen photoinduced lesions in DNA. AB - Several approaches are described aiming at a better understanding of the genotoxicity of psoralen photoinduced lesions in DNA. Psoralens can photoinduce different types of photolesions including 3,4- and 4',5'-monoadducts and interstrand cross-links, oxidative damage (in the case of 3-carbethoxypsoralen (3 CPs)) and even pyrimidine dimers (in the case of 7-methylpyrido(3,4-c)psoralen (MePyPs)). The characterization and detection of different types of lesions has been essential for the analysis of their possible contributions to genotoxicity. For example, oxidative damage photoinduced by 3-CPs can be detected by the formamidopyrimidine glycosylase (FPG) protein. Furthermore, it is shown how the presence of MePyPs induced monoadducts may interfere with the photoreactivation of concomitantly induced pyrimidine dimers, how the ratio of monoadducts and interstrand cross-links (CL) affects the occurrence of double-strand breaks during the repair of photolesions and genotoxicity. In vitro treatment of yeast plasmids, followed by transformation, also indicates that the repair of photoadducts on exogenous DNA differs for 8-methoxy-psoralen (8-MOP) induced mono and diadducts and for monoadducts alone. The recombinational rad52 dependent pathway is not needed for the repair of 8-MOP induced monoadducts. The results obtained suggest that the genotoxic effects of psoralens are conditioned by the nature, number, ratio and sequence distribution of the photolesions induced in DNA. PMID- 1432385 TI - Recent advances in the synthesis and structure determination of site specifically psoralen-modified DNA oligonucleotides. AB - We have developed novel methods for the preparation of multimicromole quantities of extremely pure, uniquely photoadducted psoralen-DNA cross-links, furan-side monoadducted DNA and pyrone-side monoadducts. Psoralen cross-linked and furan side monoadducted DNA were produced by employing high intensity argon ion and krypton ion lasers as light sources. Pyrone-side monoadducts were prepared by base-catalyzed photoreversal of psoralen cross-links. The various psoralen adducted DNA oligomers were efficiently purified by high performance liquid chromatography. These methods have permitted us to synthesize 4 mumol each of a self-complementary 8-mer d(GCGTACGC) 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) furan-side monoadduct and HMT cross-link. Preliminary nuclear magnetic resonance (NMR) data on the HMT cross-linked 8-mer d(GCGTACGC) have been obtained which confirmed the presence of the diadducted psoralen at the unique 5'TpA3' site. NMR data obtained from the 8-mer furan-side monoadduct revealed that the psoralen molecule is intercalated into the DNA double helix. Preliminary crystals of 8-mer cross-linked DNA molecule have been grown. Conditions for the growth of X-ray diffraction-quality crystals and the further analysis of these crystals are now in progress. PMID- 1432386 TI - Benzoangelicins: new monofunctional DNA photobinding agents. AB - 4,6-Dimethylbenzoangelicin, obtained by fusing a benzene ring at the furan side of 4,6-dimethylangelicin, was studied in terms of crystal structure and interactions with DNA in both ground and excited states. 4,6 Dimethylbenzoangelicin has a planar structure and forms a molecular complex with DNA, undergoing intercalation inside the double helix. Under UVA irradiation, it photoconjugates covalently with the macromolecule, showing a DNA photobinding rate slightly lower than that of 8-methoxypsoralen, involving however only its 3,4 double bond, i.e. behaving as a pure monofunctional agent. The parameters of dark binding and photobinding were determined, and two C4 cycloadducts with thymine were isolated and characterized. PMID- 1432387 TI - Synthesis and photobiological activity of new methylpsoralen derivatives. AB - The synthesis and the photobiological activity of two new derivatives of psoralen (3,4'-dimethylpsoralen and 3,4',8-trimethylpsoralen) has been described. They are congeners of the monofunctional linear furocoumarin 3,4'-dimethyl-8 methoxypsoralen. Both compounds bind very efficiently to DNA, the extent of this process being modulated by the nature of substituents at position 8. The number of photolesions is linearly related to adenine-thymine content of the nucleic acid which indicates lack of specificity for particular sequences of the nucleic acid. The structural arrangement of DNA (single stranded, double stranded, nucleosomes and chromatin) plays an additional role in affecting the photobinding process. Unlike their 8-methoxy congener the new derivatives cross-link DNA to a substantial extent. Their photobiological properties, including erythema formation, reflect very closely those of 8-methoxypsoralen (8-MOP). The conclusion can be drawn that 3,4'-dimethyl-8-MOP represents a unique derivative in its family. PMID- 1432388 TI - Current perspectives of singlet oxygen detection in biological environments. AB - There is widespread acceptance that singlet oxygen is a key intermediate on one of the pathways leading to the phenomenon of photodynamic action. However, the identification of this moiety within a particular biological system and the determination of a direct link between its presence and a particular photodynamic effect is a goal which photobiologists have hitherto failed to achieve. The aim of this review is to assess the problems associated with such a goal and methods whereby they might be overcome. Initially the general photochemical and environmental factors which govern the ability of a photosensitizer to promote photodynamic action via the intermediacy of singlet oxygen are introduced and the fundamental parameters defining the formation, decay and reactivity of this species summarized. The experimental requirements for relating a particular photodynamic effect to singlet oxygen intermediacy are then analysed and the intrinsic properties of singlet oxygen which will influence this goal are discussed. Having concluded that the singlet oxygen detection method of choice for this purpose is that in which the IR emission at 1269 nm of this molecule is monitored, the advantages and disadvantages of pulsed and continuous wave photoexcitation of cellular systems are analysed. It becomes evident that, no matter what the future improvements in instrumentation are likely to be, the inherent natures of singlet oxygen and the biological system lead to a kinetic situation which will preclude a successful time-resolved solution to this problem. In contrast, experimentation with continuous wave systems holds out significant hope for the future. In particular, the use of phase modulation techniques to overcome background emission problems, the enhancement of photosensitizer optical densities as a consequence of higher extinction coefficients and/or improved photosensitizer delivery systems and the use of high power lasers and/or improved light delivery systems can, at least in principle, lead to the solution of the problem addressed herein. PMID- 1432389 TI - Photobleaching of 1,3-diphenylisobenzofuran by novel phthalocyanine dye derivatives. AB - As part of a wider programme to identify novel photosensitizers for photodynamic therapy, the ability of a number of phthalocyanine dyes, including some novel copper phthalocyanine derivatives with a range of water solubilities, to produce potentially cytotoxic species in solution was examined. The experiments were performed in dimethylformamide using 1,3-diphenylisobenzofuran (DPIBF) as the scavenger. The study revealed that all the dyes tested produced DPIBF photobleaching on illumination in vitro, but with widely different (greater than 12x) rates. The possible correlation of DPIBF photobleaching rates with a number of the dyes' properties is discussed. PMID- 1432390 TI - Photodynamic properties of naphthosulfobenzoporphyrazines, novel asymmetric, amphiphilic phthalocyanine derivatives. AB - Metallo naphthosulfobenzoporphyrazines sulfonated to different degrees (M-NSBP) were prepared, and their potential as photosensitizers for the photodynamic therapy (PDT) of cancer was evaluated. M-NSBP can be viewed as hybrid molecules between sulfophthalocyanines and naphthalocyanines resulting in distinct differences in the absorption spectra between the mono-through tetrasulfonated derivatives. This feature greatly facilited their purification. Using V-79 Chinese hamster cells in vitro, the disulfonated derivatives were found slightly more photoactive than the hydrophilic trisulfonated derivatives while the monosulfonated derivative was inactive, in spite of a sixfold higher cell uptake. In the case of the di- and trisulfonated derivatives, differences in phototoxicity correlated well with their relative cell uptake. Substitution of Al for Zn had little effect on the extent of phototoxicity of the M-NSBP. In vitro PDT of the EMT-6 cells after in vivo dye administration, revealed a similar potency for direct cell killing between the di- and trisulfonated AlOH-NSBP, while the monosulfonated analog was inactive. PDT with the amphiphilic disulfonated AlOH-NSBP on the EMT-6 mammary tumor in BALB/c mice induced a significant tumor response, while the monosulfonated derivative was much less active. PMID- 1432391 TI - Light-induced fluorescence spectroscopy of adenomas, adenocarcinomas and non neoplastic mucosa in human colon. I. In vitro measurements. AB - In an attempt to evaluate whether induced fluorescence could be exploited to discriminate neoplastic from non-neoplastic tissue, fluorescence spectroscopy was performed at 450-800 nm on 83 biopsy specimens of colonic mucosa. Measurements showed that fluorescence spectra of adenoma, adenocarcinoma and non-neoplastic mucosa manifest dissimilar patterns. Nine variables, whose photophysical and/or biological bases need further investigation, were derived from the spectra. Discriminant functions between the groups of lesions were determined by using a stepwise discriminant analysis. The diagnostic test had a sensitivity of 80.6% and 88.2%, and a specificity of 90.5% and 95.2% in discriminating neoplastic from non-neoplastic mucosa and adenoma from non-neoplastic mucosa respectively. These results suggest that fluorescence spectroscopy has the potential to improve endoscopic diagnosis of premalignant and malignant lesions of colonic mucosa. PMID- 1432392 TI - Inactivation and mutation induction in Saccharomyces cerevisiae exposed to simulated sunlight: evaluation of action spectra. AB - The effectiveness of polychromatic light irradiation was investigated for haploid yeast cells. Inactivation and mutation induction were measured in both a RAD wildtype strain and an excision-repair defective strain. The behaviour of vegetative "wet" cells was compared to that of dehydrated cells. The aim of the study was to assess the interaction of UVC with other wavelengths in cells of different states of humidity. The irradiation procedure was therefore carried out using a solar simulator either with full spectrum or with a UVC-blocking filter (modified sunlight) added. The results were analysed on the basis of separately determined action spectra. The summation of the efficiency of individual wavelengths was compared to the values obtained from polychromatic irradiation. It is shown that the effects caused by the whole-spectrum irradiation in wet cells can be predicted sufficiently from the calculation, while dried wildtype cells exhibit higher mutation rates. Thus it can be assumed that drying-specific damage leads to lethal and mutagenic lesions which are processed in different ways, causing a synergistic behaviour in mutation induction. Irradiation of vegetative cells with modified sunlight (UVC-) results in less inactivation and lower mutation rates than were calculated. From these results it can be concluded that this antagonistic behaviour is caused by the interaction of near-UV photoproducts. PMID- 1432393 TI - UVA- and UVB-induced changes in collagen and fibronectin biosynthesis in the skin of hairless mice. AB - The modifications induced in hairless mouse skin by chronic UV irradiation were investigated. Skin explant cultures were used to study UVA- and UVB-induced changes occurring in interstitial collagen (type I and type III) and fibronectin biosynthesis. To study the long-term effects, albino hairless mice were irradiated with UVA radiation alone from two sources with different spectral qualities or with UVB. UVA and UVB radiation produced a significant increase in the ratio of type III to type I collagen (more than 100% for UVA-irradiated skin and about 60% for UVB-irradiated skin) accompanied by a significantly increased fibronectin biosynthesis (50% or more in all irradiated groups). Irradiation with either UVA or UVB alone had no significant effect on the total collagen synthesis and resulted in only a slight decrease in the total collagen content of the skin determined as hydroxyproline. This decrease was significant only in the case of the group irradiated with UVA (xenon) (decrease of 25%, expressed as micrograms of hydroxyproline per milligram wet weight). A significant decrease in collagen hydroxylation (expressed as radioactive hydroxyproline/radioactive hydroxyproline plus proline in neosynthesized collagen) was observed of about 50% in skin irradiated with UVA (xenon) but not in UVB-treated skin. Several of the above modifications (increased fibronectin biosynthesis, increased collagen type III to type I ratio) correspond to the modifications observed during the aging of non irradiated hairless mice. Therefore it appears that UV irradiation accelerates the modifications of extracellular matrix biosynthesis observed during aging. PMID- 1432394 TI - The role of low-density lipoprotein in the biodistribution of photosensitizing agents. PMID- 1432395 TI - Photodynamic inactivation of Gram-negative bacteria: problems and possible solutions. PMID- 1432396 TI - Photochemistry of nucleic acids in cells. AB - A survey of the recent aspects of the main photoreactions induced by far-UV radiation in cellular DNA is reported. This mostly includes the formation of cyclobutadipyrimidines, pyrimidine(6-4)pyrimidone photoadducts and related Dewar valence isomers in various eukaryotic and prokaryotic cells, as monitored by using either specific or more general assays. Information is also provided on mechanistic aspects regarding the formation of 5,6-dihydro-5-(alpha-thyminyl) thymine, the so-called "spore photoproduct" within far-UV-irradiated bacterial spores. The second major topic of the review deals with the effects of near-UV radiation and visible light on cellular DNA which are mostly mediated by photosensitizers. The main photoreactions of furocoumarins with DNA, one major class of photosensitizers used in the phototherapy of skin diseases, involve a [2 + 2] cycloaddition to the thymine bases according to an oxygen-independent mechanism. In contrast a second type of photosensitized reaction which appears to play a major role in the genotoxic effects of both near-UV and visible light requires the presence of oxygen. The photodynamic effects which are mediated by either still unidentified endogenous photosensitizers or defined exogenous photosensitizers lead to the formation of a wide spectrum of DNA modifications including base damage, oligonucleotide strand breaks and DNA-protein cross-links. PMID- 1432397 TI - Effect of light on calcium transport in bull sperm cells. AB - The effect of light on calcium transport was studied. Bull sperm cells were irradiated with an He-Ne (630 mm) laser and a 780 nm diode laser at various energy doses, and 45Ca2+ uptake was measured by the filtration technique. It was found that there is an accelerated Ca2+ transport in the irradiated cells, which means that laser light can stimulate Ca2+ exchange through the cell membrane. This may cause transient changes in the cytoplasmic Ca2+ concentration which, in spermatozoa, has a regulatory role in control of motility and acrosome reaction, and in other cells can trigger mitosis. PMID- 1432398 TI - An animal model for extracorporeal photochemotherapy based on contact hypersensitivity. AB - Recently, photopheresis was introduced as a specific immune suppressor in several T cell mediated disorders. In order to study photopheresis, animal models are indispensable. This report describes an easy to handle model for this purpose. It concerns the Wistar-derived rat with contact hypersensitivity (CHS), also a T cell mediated disorder that has already been studied extensively in several other fields of research. After subsequent exposure to 8-methoxypsoralen (8-MOP) and ultraviolet A radiation (UVA), white blood cells from CHS rats were intravenously injected into other syngeneic rats suffering from the same disorder. This treatment appears to be very efficacious in suppressing the immunological response against the applied contact allergen, 2,4-dinitrofluorobenzene (DNFB). Cells subsequently exposed to UVA and 8-MOP did not have any effect. PMID- 1432399 TI - Sunscreens retain their efficacy on human skin for up to 8 h after application. PMID- 1432400 TI - Substance abuse and B-cluster disorders. I: Understanding the dual diagnosis patient. AB - The patient population that presents with both a B-cluster personality disorder and substance abuse is a challenge to professionals in both the mental health and substance abuse treatment fields. The coexistence of both disorders is not uncommon and is frequently encountered in substance abuse treatment, social welfare, and mental health settings. The complexity of the clinical picture for these patients and their greater resistance to treatment severely taxes the practitioner's skills. Even without a clear understanding of the primary causative pathology, effective treatment modes based on a recognition of the interactive and interdependent nature of the two disorders can be developed. Part I of this two-part article presents the characteristics and clinical features of the population as well as a model for understanding some of the motivating principles behind the patient's conduct, feelings, thoughts. This is followed by guidelines for the clinician's attitude, desired characteristics, and role in dealing with this population. Part II presents guidelines for the treatment of this patient population. PMID- 1432401 TI - Substance abuse and B-cluster disorders. II: Treatment recommendations. AB - Part I of this two-part article described the characteristics and clinical features of the patient population that presents with both a B-cluster personality disorder and substance abuse. It also included guidelines for the clinician. Part II presents further recommendations for the treatment of this population, taking into account how the combination of these disorders manifests itself. The treatment approach should be kept simple and easy for patients to understand and should promote their ability to think rationally about the effect of their emotions on their behavior and its outcomes. A firm structure is critical to compensate for the lack of internal control of these patients and to prevent the manipulation that results from their view of the instrumentality of others. Denial, resistance, countertransference, and relapse to addictive behaviors are all potential barriers that are often encountered when attempting to treat this population. Group therapy with this population presents unique challenges to the clinician. As with individual therapy, a firm structure is imperative, with the clinician in charge of process and content. PMID- 1432402 TI - Risk and reciprocity: HIV and the injection drug user. AB - Injecting practices of illicit drug users in San Antonio, Texas, were studied by means of informal field interviews and participant observation. The methods injection drug users (IDUs) employed to obtain drugs seemed to affect their HIV risk behaviors. Many of the methods involve reciprocal exchanges between a person who has drugs and a person who wants drugs. The exchanges frequently occur in the context of asymmetrical social interactions. The person with the drugs usually occupies the dominant role in the interaction and determines the needle hygiene for both parties. Analysis of the decision-making process of IDUs indicates that the party in the dominant role may choose not to disinfect a syringe for a variety of reasons. An understanding of the subcultural rules that govern these interactions may provide valuable clues to researchers or educators who are designing interventions aimed at reducing HIV risk behaviors among IDUs. This research suggests that for IDUs in subordinate roles, education alone may be insufficient to produce behavior changes necessary to eliminate risk of HIV infection. PMID- 1432403 TI - The disease controversy and psychotherapy with alcoholics. AB - This article discusses conducting psychotherapy with alcoholics in light of the controversy about whether alcoholism is a disease. The belief that alcoholism is a disease forces many clinicians to offer abstinence from alcohol as the only option for alcoholics who seek treatment. From this perspective, the alcoholic must be helped to accept the idea that he or she has a disease and that to recover from this problem, drinking must stop. Others maintain that alcoholism may not be a disease and view alcoholic drinking as maladaptive behavior. From this vantage point, helping the patient to control or to moderate drinking might be considered. These two distinct paradigms lead to divergent treatment goals, which leaves the clinician in a quandary about how best to treat an individual who experiences a drinking problem. To resolve this dilemma, it is suggested that the clinician who works with alcoholics entertain a multiplicity of perspectives and should not be blinded by any one paradigm. While control of alcohol intake must take place if such patients are to improve their functioning, the author argues that recovery can occur either by abstinence or through moderating drinking. PMID- 1432404 TI - "Living with the dirty secret": problems of disclosure for methadone maintenance clients. AB - This article focuses on the management of stigma by methadone maintenance patients. It explores (1) the consequences of this persistent stigma, which necessitates the need for secrecy, (2) the adaptations made in order to successfully "pass as normal," and (3) the contexts in which methadone-maintained individuals decide to disclose their stigmatized status. The data reported and analyzed were gathered between 1980 and 1989 during a series of studies funded by the National Institute on Drug Abuse. The three studies--"Women on Methadone," "Getting Off Methadone," and "Alameda County Methadone Study"--utilized qualitative, in-depth interviews and ethnographic sampling techniques, primarily chain referral sampling. After ten years of interviewing women and men in various stages of their methadone maintenance careers, recurring themes emerged, one of which was that being a methadone patient is a marginal identity; not quite junkie, not quite conventional. Clients' efforts to manage this stigmatized identity were often shrouded in anguish and secrecy. Methadone patients were in a kind of identity limbo; a holding pattern between two extremely different social worlds. They were trying to effect an identity transformation; however, in many circumstances they were still associated with and defined by their "dirty secret." PMID- 1432405 TI - Smoked cocaine: patterns of use and pulmonary consequences. AB - This article offers a perspective on the use of volatilized alkaloidal cocaine in its freebase and crack forms and on the pulmonary consequences of such use. The inhalational route of administration of freebase and crack cocaine exposes the lung to their combustion products, raising concern about possible adverse pulmonary effects. A brief historical review of cocaine and its methods of use precedes the presentation of data concerning current modes and patterns of use and some pulmonary complications of crack and freebase use. Results from a systematic study of a large sample of cocaine users document a high frequency of occurrence of acute respiratory symptoms in temporal association with cocaine smoking. No relationship was detected between the prevalence of acute pulmonary symptoms and identifiable aspects of techniques of cocaine administration. These results suggest that the respiratory consequences of alkaloidal cocaine are most likely attributable to the inhaled cocaine itself, rather than to variable characteristics of usage. PMID- 1432406 TI - An overview of cocaethylene, an alcohol-derived, psychoactive, cocaine metabolite. AB - Cocaethylene is a psychoactive ethyl homologue of cocaine, and is formed exclusively during the coadministration of cocaine and alcohol. Not a natural alkaloid of the coca leaf, cocaethylene can be identified in the urine, blood, hair, and neurological and liver tissue samples of individuals who have consumed both cocaine and alcohol. With a pharmacologic profile similar to cocaine, it can block the dopamine transporter on dopaminergic presynaptic nerve terminals in the brain. It increases dopamine synaptic content, provoking enhanced postsynaptic receptor stimulation, resulting in euphoria, reinforcement, and self administration. Equipotent to cocaine with regard to dopamine transporter affinity, cocaethylene appears to be far less potent than cocaine with regard to serotonin transporter binding. Lacking the serotonergic-related inhibitory mechanism, cocaethylene appears to be more euphorigenic and rewarding than cocaine. Synthesized and administered cocaethylene has a behavioral stimulation profile similar to cocaine. Cocaethylene has been shown to be less potent and equipotent to cocaine, and alcohol plus cocaine produces more stimulatory locomotor behavior in mice than either drug alone. Equipotent to cocaine with regard to primate reinforcement and self-administration, cocaethylene can substitute for cocaine in drug discrimination studies, and can produce stimulation of operant conditioning in rats. With regard to lethality, cocaethylene has been shown to be more potent than cocaine in mice and rats. The combination of cocaine and alcohol appears to exert more cardiovascular toxicity than either drug alone in humans. Alcohol appears to potentiate cocaine hepatotoxicity in both humans and mice. PMID- 1432407 TI - Treatment of acute, adverse psychedelic reactions: "I've tripped and I can't get down". AB - The resurgence of the use of LSD by a young, inexperienced population increases the likelihood of the occurrence of adverse psychedelic reactions. While the treatment of choice remains supportive, nonjudgmental talkdown, intramuscular lorazepam and haloperidol offer invaluable and specific adjuncts to care. PMID- 1432408 TI - Methadone maintenance treatment: impact of its politics on staff and patients. PMID- 1432409 TI - Technology versus privacy: prescription accountability in the health care delivery system. PMID- 1432410 TI - Drug prescribing and the loss of liberty. PMID- 1432411 TI - Marathon therapy: treating female rape survivors in a therapeutic community. PMID- 1432412 TI - Selecting diagnostic tests to identify febrile infants less than 3 months of age as being at low risk for serious bacterial infection: a scientific overview. AB - PURPOSE: To select diagnostic tests that confidently identify febrile infants less than 3 months of age seen at an outpatient facility as being at low risk for serious bacterial infection (SBI). DATA IDENTIFICATION: An English-language literature search employing MEDLINE (1966 to 1991), Science Citation Index (1977 to 1991) using key citations, bibliographic reviews of primary research and review articles, and correspondence with authors of recent articles. STUDY SELECTION: After independent review by two observers, 10 of 333 originally identified titles were selected on the basis of prespecified selection criteria. DATA EXTRACTION: Two observers independently assessed studies by using explicit methodologic criteria for evaluating the quality of studies dealing with diagnostic tests. One reviewer extracted all the data from the articles; the second reviewer checked these data for accuracy. RESULTS OF DATA ANALYSIS: On the basis of prespecified criteria, results were pooled from two studies that used the Rochester criteria, had high methodologic validity, and did not have significant heterogeneity (p = 0.32, Breslow-Day test), to give an estimate of the best negative likelihood ratio (95% confidence interval) for SBI = 0.03; 0 to 0.23). CONCLUSION: The negative likelihood ratio of 0.03 allowed us to conclude that after the Rochester criteria for low risk of SBI have been satisfied, the probability of SBI in a febrile infant less than 3 months of age drops from a baseline rate of 7% (or 1 in 14 infants) to 0.2% (or 1 in 500). An expectant approach in these low-risk infants is therefore a reasonable choice. PMID- 1432413 TI - Defining the population of human immunodeficiency virus-infected children at risk for Mycobacterium avium-intracellulare infection. AB - We reviewed the 22 cases of Mycobacterium avium-intracellulare (MAI) infection that occurred among 196 human immunodeficiency virus-infected children seen at the National Cancer Institute Pediatric Branch from December 1986 through April 1991, and an additional 65 charts from children with cultures negative for MAI. All patients with proven MAI were receiving antiretroviral therapy with zidovudine, dideoxyinosine, or a combination of zidovudine and dideoxycytidine. All patients had disseminated MAI infection, except one adolescent who had only evidence of localized lymphadenitis. All cases of MAI but one were diagnosed before death. The overall incidence of MAI was 11% in our patients but increased to 24% in patients whose absolute CD4 cell counts were < 100 cells/mm3. Symptoms most commonly associated with MAI infection included recurrent fever (86% of patients), weight loss or failure to thrive (64%), neutropenia (55%), night sweats (32%), and abdominal pain (27%). Children infected with MAI had a mean CD4 percentage of 2% (range, 0% to 7%) and a mean absolute CD4 count of 12 cells/mm3 (range, 0 to 48 cells/mm3), significantly lower than in the remainder of the clinic population or the group of children with cultures negative for MAI. Of 20 patients with MAI infection who were tested, 10 had measurable p24 antigen with a mean value 939 pg/ml (range, 77 to 3270 pg/ml) compared with 19 of 59 patients without MAI infection in whom the mean positive value was 413 pg/ml. There was no difference in survival time between those children with documented MAI infection (median survival time, 45.5 weeks) and those with similarly low CD4 counts and cultures negative for MAI (median survival time, 50.4 weeks). Future improvements in therapeutic options may make screening of pediatric human immunodeficiency virus-infected patients with low CD4 counts a reasonable plan. PMID- 1432414 TI - Vasodilatory response of the coronary arteries after Kawasaki disease: evaluation by intracoronary injection of isosorbide dinitrate. AB - OBJECTIVE: To determine coronary artery diameter change before and after an intracoronary infusion of isosorbide dinitrate in patients who have had Kawasaki disease, we performed coronary angiography in 188 such patients. PATIENTS AND METHODS: Four patient groups were studied. Groups 1 to 3 consisted of patients with Kawasaki disease: group 1 (the "normal" group; n = 65) had no coronary artery lesions; patients in group 2 had regression to normal of a coronary artery aneurysm after Kawasaki disease and were divided, according to the time since onset, into two subgroups, group 2-a (n = 20) being at an early stage after regression to normal (followed for 1.7 +/- 0.7 years) and group 2-b (n = 34) being at a later stage after regression (followed for 8.7 +/- 2.9 years); and group 3 (the "abnormal" group; n = 25) had persistent coronary artery aneurysm or stenosis or both. Group 4, the control group (n = 44), consisted of patients without Kawasaki disease who had congenital heart disease with normal coronary arteries. The coronary artery diameter change was calculated by the following formula: Percentage of change = (Diameter after infusion - Diameter before infusion)/Diameter before infusion x 100. RESULTS: The percentages of change in the coronary artery diameter after isosorbide dinitrate infusion were 16.2% +/- 13.4% (normal group), 11.3% +/- 7.2% (early-regression group), 7.8% +/- 8.3% (late-regression group), 6.8% +/- 7.8% (abnormal group), and 15.2% +/- 11.8% (control group). In the abnormal group, there was significantly poorer dilation than in the control and normal groups. The late-regression group also had significantly less change in diameter than did the control and normal groups (p < 0.05). CONCLUSIONS: These data suggest (1) that the coronary artery after Kawasaki disease becomes stiff not only in patients with persistent abnormal lesions but also in those with regressed aneurysms and (2) that stiffness of the coronary artery may be a risk factor for atherosclerosis. PMID- 1432415 TI - Outcome of coronary artery aneurysms after Kawasaki disease. AB - From 1974 through 1991, a total of 583 children with Kawasaki disease were seen at the Hospital for Sick Children, in Toronto, of whom 80 (13.7%) had coronary artery involvement. There were 55 boys and 25 girls, whose mean age at onset was 2.9 +/- 2.5 years, followed for a mean period of 4.0 +/- 3.6 years. Giant aneurysms (maximum diameter > or = 8 mm) were found in 22 children, moderate sized aneurysms (> or = 4 to < 8 mm) in 44, and dilation lesions (< 4 mm) in 14. Myocardial infarction occurred in 9 (1.5%), all of whom had giant aneurysms. The persistence rate for aneurysms was 72% at 1 year and 41% at 5 years of follow-up. In multivariate analysis, the regression of an aneurysm was significantly related to the severity of coronary artery lesions, initial treatment, and gender. Although > 80% of small or moderate-sized aneurysms regressed within 5 years, giant aneurysms did not regress during the follow-up period. In patients who received immune globulin therapy, coronary lesions tended to resolve more rapidly than in those treated with salicylate therapy alone, because 91% of the lesions in the former were small or moderate. These findings suggest that the severity of coronary artery involvement during the initial stages of Kawasaki disease influences the regression of these lesions, and that immune globulin treatment may improve outcome by reducing the incidence of severe lesions. PMID- 1432416 TI - Independent effects of lead exposure and iron deficiency anemia on developmental outcome at age 2 years. AB - For a prospective study of lead exposure, iron status, and infant development, we recruited infants living in a smelter town and a non-lead-exposed town in Kosovo, Yugoslavia. Among 392 infants assessed at age 2 years, the mean Mental Development Index (MDI), Bayley Scales of Infant Development, was 105.2. At age 2 years, geometric mean blood lead concentrations were 35.5 and 8.4 micrograms/dl, respectively, among infants from the exposed and nonexposed towns. After controlling for variables associated with MDI, we found significant independent associations for both blood lead and hemoglobin concentrations. For example, a rise in blood lead concentration at age 2 years from 10 to 30 micrograms/dl was associated with an estimated 2.5 point decrement in MDI (p = 0.03); statistically nonsignificant decrements were associated with blood lead levels measured at birth and at 6, 12, and 18 months of age. A decrease in hemoglobin concentration at 18 months of age from 12 to 10 gm/dl was associated with an estimated 3.4 point decrement in MDI (p = 0.02); the latter association was present in both towns, suggesting that it was due to iron deficiency anemia independent of lead exposure. The findings suggest that the brain is vulnerable to the effects of both lead exposure and anemia before 2 years of age. On a global basis, the developmental consequences of anemia may exceed those of lead exposure. PMID- 1432417 TI - Responses to hypoxia and hypercapnia in infants of substance-abusing mothers. AB - Because infants of substance-abusing mothers (ISAM) have an increased risk of sudden infant death syndrome and have abnormal sleeping ventilatory patterns, we studied the effects of mild hypoxia during quiet sleep on ventilatory pattern, heart rate, and arousal in 23 healthy ISAM (mean +/- SEM: 9.0 +/- 0.49 weeks of age) and 15 healthy, similarly aged, control infants. Hypercapnic challenges were performed in six ISAM and eight control subjects. Hypoxic arousal responses were elicited by rapidly decreasing inspired oxygen tension to 80 mm Hg for 3 minutes or until arousal occurred. Failure to arouse to hypoxia occurred in the majority of infants in both groups. All infants had a fall in end-tidal carbon dioxide tension during hypoxia, suggesting that each had a hypoxic ventilatory response. However, the fall in end-tidal carbon dioxide tension was significantly less in the ISAM (mean +/- SEM: -4.0 +/- 0.3 vs -8.0 +/- 1.0 mm Hg), suggesting blunted ventilatory responses to hypoxia. Periodic breathing occurred during 9.5% of hypoxic challenges in control infants compared with 37% in ISAM (p = 0.056). Heart rates were significantly higher in the ISAM before, during, and after hypoxic challenges. Hypercapnic challenges (inspired carbon dioxide tension of 60 mm Hg for a maximum of 3 minutes) resulted in arousal in all infants; however, ISAM required a significantly longer exposure to hypercapnia before arousal (mean +/- SEM; 116 +/- 7.8 vs 79 +/- 13.9 seconds; p < 0.02). We conclude that ISAM have an impaired repertoire of protective responses to hypoxia and hypercapnia during sleep, and that this may play a role in their increased risk for sudden infant death syndrome. PMID- 1432418 TI - Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants. AB - A review of the clinical findings in six infants with nutritional vitamin B12 deficiency seen during the last 10 years was undertaken and an attempt made to obtain long-term neurologic follow-up. There was a consistent clinical pattern in vitamin B12-deficient infants; irritability, anorexia, and failure to thrive were associated with marked developmental regression and poor brain growth. Two of the four patients who qualified for long-term review had a poor intellectual outcome. Although early response to treatment is satisfying, the long-term consequences of nutritional vitamin B12 deficiency in infants emphasize the need for prevention or early recognition of this syndrome. PMID- 1432420 TI - Upper gastrointestinal tract motility in children with progressive muscular dystrophy. AB - Gastric emptying was evaluated in 15 children (mean age, 8.0 years) with progressive muscular dystrophy to detect early gastrointestinal smooth muscle involvement; 10 of the children also underwent esophageal manometry. Clinical evidence of skeletal muscle dysfunction was minimal in 14 of the 15 patients; 10 of them had no gastrointestinal symptoms. Gastric emptying studies were performed by using 500 muCi of technetium 99m-sulfur colloid bound to a scrambled egg, and scintigraphic measurements were made continuously for 60 to 90 minutes. Gastric emptying studies and manometric tracings were compared with those from 11 children (mean age, 8.4 years) without gastrointestinal or muscular disorders. Mean (+/- SD) percentage retention of gastric isotope was significantly greater in patients with muscular dystrophy than in control subjects. No differences were found between the two groups in distal esophageal motility or in upper and lower esophageal sphincter pressures or relaxation. Contraction amplitudes in the upper portion of the esophagus, however, were significantly lower in patients with myopathy than in control subjects. These data suggest that dysfunction of smooth muscle of the upper gastrointestinal tract is detectable in children with muscular dystrophy early in the course of the disease, even when gastrointestinal symptoms are absent and skeletal muscle symptoms are minimal. PMID- 1432419 TI - Hypercalciuria in children with renal glycosuria: evidence of dual renal tubular reabsorptive defects. AB - During the past 5 years, we have identified idiopathic hypercalciuria in five of seven patients referred for evaluation of renal glycosuria between 1985 and 1991. The children, all boys, ranged in age from 6 to 12 years. Endocrine function was normal, and none of the patients had hyperparathyroidism, hypercalcemia, renal tubular acidosis, or other secondary causes of hypercalciuria. The calcium/creatinine ratio in a fasting urine specimen was elevated in all five children who had hypercalciuria, with a mean value (+/- SD) of 0.34 +/- 0.06 (normal, < 0.2). In one child who had renal colic with spontaneous passage of gravel-like material, the idiopathic hypercalciuria persisted after 1 week on a diet containing 2000 mg of sodium and 300 mg of calcium. On the basis of studies that examined the site along the nephron responsible for hypercalciuria in rats with streptozocin-induced diabetes, we speculate that in children with renal glycosuria, there is defective reabsorption of glucose and calcium in the straight portion of the proximal tubule or in the collecting duct. It is likely that a similar mechanism accounts for the idiopathic hypercalciuria in children with diabetes mellitus. PMID- 1432421 TI - Hyperammonemia-hyperornithinemia-homocitrullinuria syndrome: neurologic, ophthalmologic, and neuropsychologic examination of six patients. AB - We report the clinical, electrophysiologic, ophthalmologic, and neuropsychologic features of six patients with hyperammonemia-hyperornithinemia-homocitrullinuria syndrome, an inborn error of ornithine metabolism. Pyramidal signs, decreased vibration sense, bucco-facio-lingual dyspraxia, and learning difficulties or subnormal intelligence were found in the majority. Anomalies of peripheral nerve conduction velocity and of evoked potentials were common, and one patient had markedly abnormal white matter images on cranial magnetic resonance imaging. One patient had retinal depigmentation and chorioretinal thinning. The clinical severity varied greatly among patients; in general, the three younger patients had less neurologic and intellectual impairment than did the three older patients. Only two of our patients have had episodes of symptomatic hyperammonemia. We conclude that hyperammonemia-hyperornithinemia homocitrullinuria syndrome can be associated with widespread manifestations in the central and peripheral nervous systems. Although the control of hyperammonemia is an essential element in the treatment of these patients, the relationship of hyperammonemia to the chronic neuropsychologic problems of these patients is unclear. PMID- 1432422 TI - Long-term issues in Kawasaki disease. PMID- 1432423 TI - Arcanobacterium haemolyticum in children with presumed streptococcal pharyngotonsillitis or scarlet fever. AB - Arcanobacterium haemolyticum was cultured from pharyngeal specimens obtained from 12 of 129 children with pharyngotonsillitis, some of whom had a scarlatiniform rash. This organism should be considered to be a cause of infections that are clinically similar to those caused by beta-hemolytic streptococci. PMID- 1432424 TI - Soft tissue swelling and acute skull fractures. AB - To determine whether soft tissue swelling, as identified by computed tomography, invariably accompanies acute calvarial fracture, the computed tomography scans of 35 children aged 3 months to 8 years with acute skull fractures were evaluated. Bone window settings revealed at least 4 mm of soft tissue swelling in all instances. We conclude that a skull fracture without overlying soft tissue swelling demonstrable by computed tomography is probably inconsistent with an acute injury. PMID- 1432425 TI - Pancreatitis heralding Kawasaki disease. AB - A 5 1/2 year-old boy was hospitalized with clinical and laboratory evidence of pancreatitis. Four days later the classic signs and symptoms of Kawasaki disease developed. This case suggests that Kawasaki disease should be included in the differential diagnosis of acute pancreatitis in children. PMID- 1432426 TI - Autoantibody production after cardiopulmonary bypass with special reference to postpericardiotomy syndrome. AB - A prospective study of children undergoing open heart surgery with cardiopulmonary bypass showed that many of them produced autoantibodies. No association was found between these antibodies, including anticardiolipin antibodies, and the occurrence of postpericardiotomy syndrome. PMID- 1432427 TI - Benign acute myositis associated with rotavirus gastroenteritis. AB - Acute myositis developed concomitantly with gastroenteritis in a 2-year-old girl. She had temporary pain and swelling of the calf muscles and transient marked elevation of serum creatine kinase values. Rotavirus antigen was detected in stool by latex agglutination, and there was seroconversion of complement-fixation antibody to rotavirus. PMID- 1432428 TI - Variability of clinical presentation in fumarate hydratase deficiency. AB - A 5-year-old girl with a previous diagnosis of cerebral palsy, nonprogressive psychomotor retardation, and hypotonia was found to excrete excessive fumaric acid in urine. Fumarate hydratase activity in skin fibroblasts was 10% of the control value. This case underscores the clinical heterogeneity of neurometabolic disorders and the importance of organic acid analysis in the diagnosis of static encephalopathy. PMID- 1432429 TI - Charting infant distress: an aid to defining colic. AB - The value of a 24-hour distress diary, previously validated against a voice activated audiotape record, was investigated in 30 infants with colic and 30 control infants. The infants with colic had significantly more distress behavior (300.0 minutes vs 102.5 minutes; p < 0.001), although overlap of duration of distress was noted. On the basis of a clinical definition of colic--total distress lasting 180 minutes in a 24-hour period--the diary had a sensitivity of 77% and a specificity of 87%. The sensitivity of the chart was confirmed in a separate study of another 90 infants with colic. PMID- 1432430 TI - Effect of liposomal content of lipid emulsions on plasma lipid concentrations in low birth weight infants receiving parenteral nutrition. AB - We studied the effects of phospholipid liposomes present in intravenously administered lipid emulsions on plasma lipid levels in preterm infants given 10% and 20% lipid emulsions. Twenty premature infants (birth weight 1454 +/- 54 gm) on a parenteral nutrition regimen received up to 4 gm triglycerides per kilogram per day in a 20% lipid emulsion for 2 weeks, and then received the 10% emulsion at 2 gm triglycerides per kilogram per day, which delivered the same total phospholipid load but twice the amount of liposomes. Triglyceride, total cholesterol, and phospholipid concentrations increased significantly when the infants were given 2 gm triglycerides per kilogram per day in the 10% emulsion rather than 4 gm/kg per day in the 20% emulsion (44 +/- 4 to 57 +/- 5 mg/dl, 134 +/- 6 to 162 +/- 9 mg/dl, and 204 +/- 8 to 251 +/- 10 mg/dl, respectively). Lipoprotein analysis indicated the presence of lipoprotein X-like particles in the low-density lipoprotein fraction and an increase of the intermediate-density lipoprotein fraction in infants who received the 10% emulsion. The presence of excess phospholipids in the 10% emulsion was associated with greater plasma lipid alterations. Therefore the use of 20% rather than 10% emulsion allows for more efficient triglyceride clearance, even at a higher triglyceride intake. Administration of emulsions that are relatively poor in phospholipid liposomes may allow delivery of > 2 gm triglycerides per kilogram per day to low birth weight infants. PMID- 1432431 TI - Role of delayed feeding and of feeding increments in necrotizing enterocolitis. AB - In spite of a number of studies on necrotizing enterocolitis, there remains controversy concerning prevention regimens, especially with regard to enteral alimentation. This report is of a matched case-control study of the relationship of necrotizing enterocolitis to timing of first feeding, size of feeding volumes and increments, and a risk factor index in 59 case patients with necrotizing enterocolitis and 59 matched control patients. Comparison with control patients showed that case patients were fed earlier, received full-strength formula sooner, and received larger feeding volumes and increments. More highly stressed infants, as measured by the risk index, were more vulnerable to larger feeding increments. Among case patients there was significant correlation of age at first feeding and age at diagnosis (p < 0.0001) even after control for birth weight and risk index score, indicating that delayed feeding was related to delayed onset of disease. These analyses support the theory that earlier, more rapid feeding places stressed infants at greater risk for the development of necrotizing enterocolitis, and that infants with more severe respiratory problems are more vulnerable to such feeding practices. PMID- 1432432 TI - Effect of dopamine on failure of indomethacin to close the patent ductus arteriosus. AB - To test the hypotheses that administering dopamine before and concurrently with indomethacin therapy would (1) increase successful ductal closure rate, (2) act by maintaining a diuresis, and (3) prevent oliguria or high serum creatinine concentrations, we conducted a randomized, controlled trial in infants whose gestational age was <36 weeks and who had hemodynamically significant ductus arteriosus. Thirty-six infants were selected to receive a continuous infusion of either placebo or dopamine at either a low dosage of 2 micrograms/kg per minute or a higher dosage of 5 micrograms/kg per minute, beginning 6 hours before the use of indomethacin and continuing until 12 hours after the third dose of indomethacin. A total of 12 patients were selected to receive placebo, 14 were selected to receive "low dopamine," and 10 were selected to receive "high dopamine." The three groups were similar in their initial characteristics. Serum creatinine concentrations, urine output, and fractional excretion of sodium were not different in the three groups after indomethacin treatment. Two patients receiving placebo required a second course of indomethacin compared with four patients in the low-dopamine group and one in the high-dopamine group. The proportion of failures of medical treatment was not statistically different among the three groups. We conclude that concomitant dopamine therapy neither decreases the failure rate in indomethacin-treated infants nor reduces the magnitude of the indomethacin-induced oliguria. PMID- 1432433 TI - Risk factors for early intraventricular hemorrhage in low birth weight infants. AB - Because earlier studies suggested that preterm infants with germinal matrix hemorrhage or intraventricular hemorrhage or both (GMH/IVH) present within the first 12 postnatal hours are at greatest risk for the development of high-grade hemorrhage and neurodevelopmental disability, we examined the risk factors for this insult among 229 neonates of 600 to 1250 gm birth weight in a multicenter study. All had echoencephalography (ECHO) within the first 11 hours and serially for the next 20 days; risk factor data were collected prospectively. Forty-three infants had GMH/IVH within the first 5 to 11 hours (mean age at ECHO 7.7 hours): 18 GMH and 21 grade II, 1 grade III, and 3 grade IV IVH. One hundred eighty-six infants did not have GMH/IVH at a mean age of 7.9 hours. Both groups of infants were similar in birth weight, gestational age, maternal risk factors, cord pH values, and surfactant therapy before ECHO. The group with early IVH had more vertex presentations than the group without early IVH (79% vs 55%, p = 0.043), less maternal tocolytic use (42% vs 60%, p = 0.029), and more vaginal deliveries (67% vs 44%, p = 0.005). In the first 21 days, severe IVH developed in 12 infants with early IVH and in 6 infants without early IVH (p < 0.001). There were more neonatal deaths (16% vs 6%, p = 0.035) and more deaths at any time during the primary hospitalization (23% vs 9%, p = 0.010) among the early IVH group than among the group without early IVH. Multivariate analysis indicated that the mode of delivery, fetal presentation, and birth weight were important and independent prognostic indicators of IVH. PMID- 1432434 TI - Renal function in very low birth weight infants: normal maturity reached during early childhood. AB - Development of glomerular and tubular renal function is delayed in preterm infants. To study the pattern of maturation during infancy and childhood, we re evaluated renal function in 22 very low birth weight infants--in 14 of the infants at 18 months postconceptional age (9 months corrected age) and in the remaining 8 infants at 8 years of age. The glomerular filtration rate remained lower at 9 months corrected age than in term infants of the same postconceptional age: 82 +/- 23 versus 125 +/- 18 ml/min per 1.73 m2 (p < 0.001). At 8 years of age the glomerular filtration rate did not differ from that of healthy control subjects. Effective renal plasma flow, filtration fraction, albumin excretion, maximal concentrating ability, and kidney size determined by ultrasonography were all normal at 8 years of age. We conclude that renal function, which is markedly reduced during the neonatal period in very low birth weight infants, reaches normal maturity by 8 years of age but not by 9 months corrected age. PMID- 1432435 TI - Cognitive and behavioral deficits in nonhuman primates associated with very early embryonic binge exposures to ethanol. AB - This study was undertaken to evaluate teratogenesis associated with early weekly ethanol exposure followed by later gestational abstinence. Ethanol, 1.8 gm/kg, was orally administered weekly to gravid nonhuman primates (Macaca nemestrina) for the first 3, 6, or the entire 24 weeks of pregnancy. Control animals received weekly sucrose solution as did the 3- and 6-week cohort animals in subsequent weeks. Thirty-five viable infants were assessed for growth, malformations, and behavioral and cognitive dysfunction. Animals in the 6-week and 24-week cohorts were uniformly abnormal in behavior and inconsistently abnormal in physical development relative to the control animals. Animals in the 3-week cohort were equivocally normal. These results demonstrate ethanol's capacity to produce behavioral teratogenesis (brain dysfunction) in isolation from physical anomalies in the rest of the body. The results strongly suggest that binge drinking in the first 6 to 8 weeks of pregnancy (a period when women may not know that they are pregnant), followed by later gestational abstinence, is as dangerous to the fetus as exposure throughout gestation. PMID- 1432436 TI - Effect of therapy with a new glucocorticoid, deflazacort, on linear growth and growth hormone secretion after renal transplantation. AB - Deflazacort is an oxazoline compound derived from prednisolone with similar antiinflammatory effects but fewer side effects. We studied changes in kidney function, growth velocity, weight/height ratio, and growth hormone secretion before and a year after substitution of deflazacort for methylprednisone in nine patients aged 9 to 15 years, 4 years after renal transplantation; all were in Tanner pubertal stage 1. Methylprednisone (mean +/- SEM: 0.2 +/- 0.02 mg/kg per day) was replaced by deflazacort (0.3 +/- 0.03 mg/kg per day) for a mean period of 15 months. Serum creatinine and calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 1.5 +/ 0.3 to 3.2 +/- 0.5 cm/yr (p < 0.005) in the nine patients. Weight/height ratio decreased from 28.4% +/- 8.5% to 16% +/- 6.7% (p < 0.005). Cushingoid appearance decreased in all patients. Mean spontaneous growth hormone secretion increased from 2.5 +/- 0.4 to 4.4 +/- 1.2 ng/ml (p < 0.05). Our findings indicate that immunosuppressive treatment with deflazacort is as effective as methylprednisone and is associated with fewer side effects. PMID- 1432437 TI - Low recovery in vivo of highly purified factor VIII in patients with hemophilia. AB - To assess whether the response and recovery of highly purified factor VIII products approach the levels predicted by use of manufacturers' suggestions, we studied response in vivo and percentage of recovery in boys and men with hemophilia after infusion of 50 IU of an immunoaffinity-purified factor VIII preparation (Hemofil M) per kilogram of body weight. We also studied dose response and percentage of recovery in the same boys after infusion of a factor VII concentrate prepared by solvent detergent treatment and gel filtration (Koate HP). For boys the difference between mean peak factor VIII response with Hemofil M (1.02% +/- 0.07%) and the response with Koate-HP (1.21% +/- 0.10%) was not significant (p = 0.10), but the response of both products was considerably less than the predicted response of 2.0%. The response to Hemofil M in men (1.38% +/- 0.12%) was significantly better than the response in boys (p = 0.004) but, again, fell short of the anticipated response of 2.0%. In boys the percentage of recovery of Hemofil M was 38.4% +/- 2.1%, compared with Koate-HP recovery, which was 47.0% +/- 3.6% (p = 0.034). The percentage of recovery in men was 47.5% +/- 2.8%. The better response observed in men appears to be, in part, a function of larger body size. We conclude that peak factor VIII response and recovery in boys and men who receive highly purified factor VIII concentrates are lower than those predicted by use of current prescribing recommendations. PMID- 1432438 TI - Effect of add-on amantadine therapy for refractory absence epilepsy. AB - Amantadine hydrochloride was administered as an add-on drug to four children with refractory absence epilepsy, resulting in complete resolution of absence episodes within 1 week. All patients remained free of symptoms for 27 to 36 months without adverse effects related to this drug. An attempt to discontinue the use of this medication in three children resulted in a prompt relapse. The suggestion that amantadine may be an effective drug in the treatment of refractory absence epilepsy, should be tested in a double-blind, controlled study. PMID- 1432439 TI - Pharmacokinetics and pharmacodynamics of erythropoietin during therapy in an infant with renal failure. AB - We treated an infant with anemia and chronic renal failure with recombinant human erythropoietin (300 to 750 U/kg subcutaneously per week) and iron (6 mg/kg enterally) from 1 to 4 months of age. A suboptimal pharmacodynamic response was seen at the lower dose. This may have been due to developmental erythropoietin pharmacokinetic differences, that is, relatively greater neonatal plasma clearance and steady-state volume of distribution compared with those in adults. PMID- 1432440 TI - Unforgettable patients. PMID- 1432441 TI - Unforgettable patients. PMID- 1432442 TI - Congenital nasal stenosis in newborn infants. PMID- 1432443 TI - Criteria for exclusion of serious bacterial infections in young infants. PMID- 1432444 TI - Moebius syndrome in an infant exposed in utero to benzodiazepines. PMID- 1432445 TI - Serum valproate concentrations and control of seizures. PMID- 1432446 TI - Risk of acyclovir therapy in pregnant adolescent. PMID- 1432447 TI - Detection of ingested foreign bodies with a metal detector. PMID- 1432448 TI - Neurologic abnormalities in sickle cell disease: role of meperidine. PMID- 1432449 TI - The insufficiency of single point diffusive air flow integrity testing. PMID- 1432450 TI - Presentation: Basel International Congress. Advanced technologies for Manufacturing of Aseptic & Terminally Sterilized Pharmaceuticals & Biopharmaceuticals. PMID- 1432451 TI - Improved direct epifluorescent filter technique for rapid bioburden control in intravenous solutions. AB - Epifluorescence microscopy of the microcolonies obtained after filtration of a deliberately contaminated intravenous solution, was used for the rapid detection and enumeration of the bacteria. The technique is adequate for the test of low volume solution (with low contamination). Also it allows one to detect a single colony forming unit (c.f.u.)/mL, with great correlation between fluorescence counts and pour plate colony counts; the morphology of microcolonies is typical for most of the microorganisms and it allows a primoidentification (for a trained analyst). PMID- 1432452 TI - A novel method of determination of protein stability. AB - A novel method of determination of protein stability is described, which involves interfacial shear rheology of adsorbed protein layers. This technique provides information on the structural-mechanical properties of the adsorbed protein layers which can be related to: the rate of interfacial adsorption, interfacial interactions, and conformational changes in the adsorbed layers. The interfacial shear rheology of the blood proteins, bovine serum albumin and human immunoglobulin G was investigated. The air/aqueous and oil/aqueous interfaces were studied and the interfacial rheological activity of BSA was shown to be similar at three hydrophobic interfaces: air, squalene and mineral oil. The kinetics of interfacial film formation was shown to be time dependent, and aging effects were detected in both interfacial and bulk molecules. The absolute interfacial elasticity values decreased as the temperature increased. The protein solutions exhibited no interfacial rheological activity in the presence of the small surfactant molecules, Tween 80 and lecithin, under the conditions studied. PMID- 1432453 TI - Validation of automated systems--system definition. AB - A Parenteral Drug Association (PDA) Committee on Software Validation was formed about three years ago to address some of the issues associated with validating automated systems, particularly where all, or part, of the automated system is supplied by outside vendors. A Technical Report that describes a process which emphasizes system definition, a comprehensive system specification, system qualification and ongoing evaluation will issue later this year. The concepts described in this document will be consistent with the PMA's System Development Life Cycle approach which is commonly used for computer system validation. The following article has been developed from the System Definition section of this PDA Technical Report. PMID- 1432454 TI - The role of the effective concentration in interpreting hemolysis data. AB - Problems inherent in traditional methods of determining the hemolytic activity of parenteral compounds are discussed. Data taken from a study which closely models the conditions present for an intravenous injection are re-examined. An equation is given which combines several variables into a single parameter, the effective concentration. A strong relationship is found between the effective concentration of the compound of interest and the hemolysis produced. PMID- 1432455 TI - "Points to consider" in the validation of equipment cleaning procedures. AB - Cleaning validation has received increasing attention by the FDA in recent inspections, yet very little has been published regarding practices within the pharmaceutical industry. This presentation will review several of aspects of the validation of equipment cleaning procedures. A significant portion of the presentation is derived from round table discussions the author has led over the last several years on this subject. Specific areas to be defined include: sampling methods, analytical methods, physical parameters, and of greatest interest, the selection of acceptance criteria. The presentation also includes some additional perspectives on the subject of cleaning validation developed by the author which may prove useful to the practitioner. PMID- 1432457 TI - Industrial perspective on validation of tangential flow filtration in biopharmaceutical applications. Technical Report No. 15. Parenteral Drug Association. Biotechnology Task Force on Purification and Scale-up. AB - Validation of tangential flow filtration is required to ensure the process delivers a product of consistent quality, safety, and efficacy. A thorough and sound validation program not only satisfies regulatory requirements, but also provides a valuable source of information which facilitates development of future processes, training of production personnel, and trouble shooting for the validated process. Validation of TFF shares many common elements with validation of other traditional operations and equipment. Existing personnel and procedures should be readily adapted to execute the TFF validation protocols. IQ's and OQ's will most likely follow familiar formats. In performance qualification, key areas needing attention include: assessment of compatibles, testing of parameters affecting membrane retention and selectivity, cleaning, sanitization, and membrane lifetime. Finally, the hallmark of a sound validation program is the quality of its scientific approach and its congruence with the definition of validation contained in the 1987 guidelines (6). PMID- 1432456 TI - Reduction of bioavailability of aluminium in neonatal parenteral nutrition solutions by prior complexation in the dosage form. AB - Aluminium (Al ) is abundant in our environment and is a contaminant of electrolyte solutions used in the manufacture of Total Parenteral Nutrition (TPN) solutions administered to neonates, who are unable to tolerate oral feeding. Previous studies by McHalsky et al. (1) have shown concern over the levels of aluminium in parenteral products, and there are special considerations needed with regard to neonatal TPN solutions, (2). It is felt that neurotoxicology and abnormalities of bone histology may be seen with aluminium deposition in the tissues. In the present study it was shown that the average aluminium contamination in TPN solutions was in the order of 205 micrograms/L. It is well documented that aluminium is chelated successfully in dialysis solutions by desferrioxamine (DFO), Allain et al. (3). Using an AA spectrophotometer equipped with a graphite furnace, the average amount of aluminium in compounded neonatal TPN solutions was determined. Equimolar amounts of DFO to aluminium were added to various neonatal TPN formulations, and the physical stability of each solution was determined using microscopic and electronic particle counting analysis. This study suggests that aluminium can be irreversibly chelated with DFO and stable TPN solutions can be prepared. PMID- 1432458 TI - Hepatic fibrogenesis and its modulation by growth factors. PMID- 1432459 TI - Specialty lipids for infant nutrition. I. Milks and formulas. PMID- 1432460 TI - Does the fecal flora of breast-fed infants limit gastroenteritis? PMID- 1432461 TI - Volatile fatty acids, lactic acid, and pH in the stools of breast-fed and bottle fed infants. AB - We measured fecal pH, volatile fatty acids (VFA), and lactic acid concentrations in 67 healthy infants ranging in age from 1 to 5 months. The babies were divided into five groups according to their diet: group 1: human milk, with subgroups of 1 month of age (n = 8), and 2-5 months (n = 12); group 2: formula milk, with subgroups of 1 month of age (n = 9) and 2-5 months (n = 10); group 3: cow's milk, one group of 2-5 months of age (n = 12); group 4: human milk supplemented with formula milk, 2-5 months of age (n = 8); and group 5: human milk supplemented with cow's milk, 2-5 months of age (n = 8). Fecal VFA concentration and pH of bottle-fed infants (groups 2 and 3) were significantly higher and lactic acid concentrations significantly lower than those of the breast-fed group. Groups 4 and 5 showed significantly higher pH and propionic acid concentration, and lower lactic acid concentration than Group 1 did. There were no significant differences in the data on pH, VFA, and lactic acid concentrations between the feces of formula and cow's milk groups. On the other hand, the addition of formula or cow's milk to the human milk was sufficient to alter the profile of VFA, the pH, and the lactic acid concentration of breast-fed infants stools. Low pH, low VFA, and high lactic acid concentrations make the colonic content of breast-fed babies an environment favorable for Bifidobacteria growth, and this is probably the main protective factor against gastrointestinal infections. PMID- 1432462 TI - Efficient assimilation of lactose carbon in premature infants. AB - Previous studies have shown that there is minimal fecal excretion of carbohydrate energy in premature infants with high breath H2 concentrations, implying that the colon plays an important role in salvaging lactose energy. The present study extends this work by using a stable isotope method for serial assessment of lactose carbon excretion. Thus, in nine premature infants (30-32 weeks of gestation and 11-36 days of age), we conducted 23 longitudinal studies of breath hydrogen concentration and the cumulative fecal excretion of 13C derived from a single dose of [D-1-13C]lactose. The ranges of values (mean +/- SD) for breath hydrogen concentration and lactose absorption were respectively 4-440 ppm/5% CO2 (92 +/- 100) and 82-100% tracer dose (98.4 +/- 3.9). In 21 studies, lactose carbon excretion was less than 2% of the dose. There was a significant correlation between postnatal age and breath hydrogen concentration (R = 0.48; p = 0.02). These studies suggest that colonic fermentation activity is adequate for efficient colonic salvage of lactose even during the second week of life. PMID- 1432463 TI - Developmental changes in lactase-phlorizin hydrolase precursor isoforms in the rat. AB - The purpose of this study was to determine whether the developmental decline in lactase specific activity (mumol/min/g protein) in the rat was associated with (a) changes in the relative quantities of immunoisolated precursor and mature forms of the enzyme purified by SDS-PAGE and/or (b) immunohistologic changes in the jejunal mucosa. We studied 10- and 16-day-old suckling rat pups, 22-day-old weaned rat pups, and adult female rats (nongravid, pregnant, and lactating). Lactase activity was three- to fourfold higher in 10-day-old pups than in adult rats. Lactase activity was 27% greater in lactating compared with nongravid or pregnant rats. Three molecular forms of the enzyme that migrated identically in all animals were observed on SDS-polyacrylamide gels stained with Coomassie blue: 140-kDa (mature brush border form), 200-kDa, and 220-kDa (apparent precursor forms). There was a striking difference in the proportions of the three polypeptides at different ages that was unrelated to animal status, i.e., pregnant or lactating. As the animals aged, the relative amount of the 140-kDa band declined from 86 +/- 1.1% of the total immunoprecipitated lactase in 10-day old suckling pups to 68 +/- 0.7% in adults. Simultaneously, the relative concentration of the 200-kDa band rose from 1.7 +/- 0.4% in the 10-day-old to 19 +/- 0.6% in adults. The relative concentration of the 220-kDa polypeptide did not change as a function of age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432464 TI - Iron absorption and incorporation into red blood cells by very low birth weight infants: studies with the stable isotope 58Fe. AB - Measurements of iron absorption and incorporation into RBCs were obtained with the stable isotope 58Fe, administered as a reference dose, in 11 premature infants with birth weights between 780 and 1,520 g and gestational ages between 24 and 33 weeks. Each study included a timed stool and urine collection, nasogastric tube administration of a single dose of about 228 micrograms of 58Fe/kg of body weight (as FeSO4, with 10 mg/kg of vitamin C) between feedings, and blood samples before 58Fe (day 1) and then 2 weeks (day 15) later. Gastrointestinal absorption of the 58Fe dose as measured by fecal isotope balance was 41.6 +/- 17.6% (mean +/- SD). However, only 12.0 +/- 9.6% of the 58Fe dose (28.7 +/- 22.3% of the absorbed 58Fe dose) was incorporated into RBCs on day 15. 58Fe absorption and 58Fe incorporation into RBCs on day 15 were significantly correlated with the hemoglobin concentration and reticulocyte count on day 1. Transfusion history did not affect 58Fe absorption or 58Fe incorporation into RBCs. We conclude that concurrent measurement of 58Fe absorption with fecal monitoring and of 58Fe incorporation into RBCs permits a better understanding of the fate of iron ingested by premature infants than either measurement alone. PMID- 1432465 TI - Surfactant-like material in the antral gastric mucosa of children. AB - It has been proposed that the hydrophobicity of the gastric mucosa is due to surfactant-like material (SLM), mainly composed of phospholipid, adsorbed to the mucosal surface. Biochemical and physiological studies have been performed in different mammals but morphological data on children are lacking. In the present work, the presence of SLM on the antral gastric mucosa of children has been studied by electron microscopy. The results demonstrate that SLM is present and shows two different forms, lamellar bodies and lamellar layers. In the mucosae without endoscopic, histologic, and ultrastructural alterations we have found SLM when the tannic acid method has been used but not when the tissue has been fixed only in glutaraldehyde. Our results suggest that in children with ultrastructural alterations of the epithelium, the amount of gastric SLM is increased in respect to children with a normal mucosa and that the amount of SLM on the surface of the gastric antral mucosa is modified in pathologic conditions. PMID- 1432466 TI - Low bone mineral content in summer-born compared with winter-born infants. AB - Possible seasonal differences in newborn bone mineral content (BMC) have not been studied. Adult studies show seasonal variations with lower BMC in winter versus summer. Assuming that BMC variations may relate in part to vitamin D status, we hypothesized that newborn BMC would be lower in winter than summer. BMC of one third distal radius was measured in 55 healthy term newborns using a single beam photon absorptiometer [coefficient of variation (CV) for phantom standard 2.1%]. Infants were enrolled during summer (July-September, 1988) and winter (January March, 1989) for a longitudinal nutrition study. Contrary to our hypothesis, there was a 12% lower BMC in summer versus winter (mean +/- SD 75.94 +/- 17.42 vs. 86.55 +/- 17.54 mg/cm, respectively; p = 0.035). The difference remained significant after controlling for possible race and gender effects (p = 0.02). We conclude that BMC is lower in summer- compared with winter-born infants. Since any seasonal effects on fetal bone are presumably related to effects through the mother, we speculate that if maternal vitamin D status influences fetal bone mineralization, the effect (possible sunshine deprivation in winter) may operate especially in early pregnancy, thus resulting in lower BMC, evident at birth in summer. PMID- 1432467 TI - Impact of zinc supplementation on intestinal permeability in Bangladeshi children with acute diarrhoea and persistent diarrhoea syndrome. AB - Zinc has been shown to enhance intestinal mucosal repair in patients suffering from acrodermatitis enteropathica; but the impact on mucosal integrity during acute (AD) or persistent (PD) diarrhoea is unknown. One hundred eleven children with AD and 190 with PD aged between 3 and 24 months received, randomly and blind to the investigators, either an elemental zinc supplement of 5 mg/kg body wt/day or placebo in multivitamin syrup for 2 weeks while intestinal permeability and, biochemical and anthropometric markers were serially monitored. The permeability test was administered as an oral dose of 5 g lactulose/l g mannitol in a 20-ml solution followed by a 5-h urine collection. The ratio of the urinary probe sugars was correlated to clinical, biochemical, and microbiological parameters. At presentation, lactulose excretion was increased and mannitol excretion decreased in both AD and PD as compared with age-matched asymptomatic children. The lactulose/mannitol ratio (L/M) was higher in subjects with mucosal invasive pathogens (rotavirus and enteropathogenic Escherichia coli) compared with children excreting Vibrio cholera and enterotoxigenic E. coli. Two-week zinc supplementation significantly reduced lactulose excretion in both AD and PD, whereas the change in mannitol excretion and L/M was similar between study groups in both studies. Changes in lactulose excretion were significantly influenced by zinc supplementation in children with E. coli, Shigella sp., and Campylobacter jejuni stool isolates. The greatest reduction in total lactulose excretion was seen in supplemented children who on presentation were lighter (wt/age less than 80%), thinner (wt/ht less than 85%), and undernourished [middle upper arm circumference (MUAC) less than 12.5 cm] or with hypozincaemia (less than 14 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432468 TI - Gastric emptying using three different formulas in infants with gastroesophageal reflux. AB - The role of delayed gastric emptying (GE) in the pathogenesis of gastroesophageal reflux (GER) in infants is controversial at present. GE has been shown to be altered by the composition and osmolality of the feedings. This prospective study was undertaken to assess the changes in the GE and the percentage of time GER was detected by scintigraphy using three different formulas on consecutive days in infants with GER. Twenty-eight infants under 1 year of age diagnosed to have GER by extended intraesophageal pH monitoring (pH being less than 4.0 for greater than 5% of the duration of the test), underwent scintigraphy on three consecutive days using the same volume per single feeding of a casein-predominant, soy, or a whey-hydrolysate formula in a randomized order. The formulas were isocaloric. Gastric emptying and percentage of GER into the esophagus were estimated for 60 min following these feedings. Mean GER percent during the study was 20.39, 17.68, and 16.34 on casein-predominant, soy, and whey-hydrolysate formulas, respectively, and was not significantly different. Mean values of GE were 39.7%, 44.6%, and 48.5% on casein, soy, and whey formula, respectively. No significant difference in GE was also observed between casein-predominant and soy formula. However, a significant difference was observed (p less than 0.05) on GE between casein-predominant and whey-hydrolysate feedings. Our data suggest that formula selection may be important in the treatment of conditions associated with delayed gastric emptying. PMID- 1432469 TI - ELISA method for quantitative measurement of IgA and IgG specific anti-gliadin antibodies. AB - In this study we describe the application of an enzyme-linked immunosorbent assay (ELISA) for the measurement of anti-alpha-gliadin antibodies (AGA) in absolute units (microgram protein/ml). Enriched samples of IgA and IgG AGA were obtained by means of protein A chromatography after immunoaffinity purification of pooled sera from untreated celiac patients. No cross-reactivity with other food antigens (beta-lactalbumin, soya proteins, ovalbumin) was detected. The quantitative evaluation of protein content in IgA and IgG AGA samples obtained by immunoaffinity chromatography, was performed by means of ELISA sandwich method using a reference curve obtained with pure standard human immunoglobulins. Scalar concentrations of purified IgA and IgG were then used to obtain a reference standard curve by means of an ELISA method. Such standard curve was utilized for titrating AGA in 214 sample sera. The minimal detectable concentration of IgA and IgG AGA was 0.02 micrograms/ml. The reproducibility of within- and between-assay resulted very good for IgA-AGA and acceptable for IgG-AGA. The method here described seems to be satisfactory not only for quantitative diagnostic purposes in routine screenings but also in epidemiological studies. Moreover, it can constitute a suitable way to solve practical problems of quality control of AGA ELISA assay. PMID- 1432471 TI - Adverse food reactions. PMID- 1432470 TI - Postnatal development of liver and exocrine pancreas in polycythemic newborn infants. AB - In 35 newborn infants appropriate for gestational age the influence of neonatal polycythemia (venous hematocrit greater than 60% measured between the second and fourth hour of life) on development of enterohepatic circulation of bile acids, activities of pancreatic enzymes in duodenal juice, and the effects of hemodilution were studied during the second week of life. A significant correlation was found between the initial hematocrit and both the bile acid concentration in serum and lipase and trypsin activity in duodenal juice. Of 35 infants, 10 were not treated with hemodilution due to asymptomatic polycythemia; they had the highest concentration of serum bile acids associated with the lowest lipase and trypsin activity in duodenal juice. However, the 25 infants treated with hemodilution also showed serum bile acid concentrations and lipase and trypsin activity in duodenal juice out of the normal range when compared to normocythemic infants. These data indicate that, during the first days of life, polycythemia results in a delayed postnatal development of enterohepatic circulation of bile acids and exocrine pancreas functions independently from the occurrence of clinical symptoms. Thus, it can be concluded that, on the first day of life, all polycythemic infants should be treated with hemodilution. Moreover, the nutritional management of these infants must also account for the limited functional capacity of the gastrointestinal tract. PMID- 1432472 TI - Rice-induced anaphylactoid reaction. PMID- 1432473 TI - Neonatal hemochromatosis: report of successful orthotopic liver transplantation. PMID- 1432474 TI - Atypical genital involvement in a child with Crohn's disease. PMID- 1432475 TI - Nutritional therapy for ulcerative colitis? PMID- 1432476 TI - Somatostatin and the pancreas. PMID- 1432477 TI - Defining the functions of cholecystokinin. PMID- 1432478 TI - Retrovirus infection of enterocytes: do they or don't they? PMID- 1432479 TI - Theory-driven research in pediatric psychology: a little bit on why and how. AB - Introduces a Special Issue, covering two published issues (5 and 6) of this journal, on theory-driven research in pediatric psychology. A rationale for conducting research from a conceptual basis is presented. It is emphasized that science is primarily an intellectual activity, demonstrated in the form of theory building, testing, and reformulation. Furthermore, it is argued theory serves as a planning and communication aide for scientific pursuit. The process and components of theory-driven research are then highlighted. Theoretical constructs, theoretical and empirical definitions of constructs, and the use of variables are discussed. A definition of scientific theory is offered. Theory testing is distinguished from post hoc theorizing. Differences in the scope of theories are noted. Connections between theory and hypothesis testing and research design are addressed, especially for nonexperimental or correlational research. PMID- 1432480 TI - A longitudinal analysis of adherence and health status in childhood diabetes. AB - Applied structural equation modeling to a longitudinal data set of 193 youngsters with insulin-dependent diabetes mellitus assessed on two occasions, an average of 1.65 years apart. Six adherence constructs, Injection, Exercise, Diet Type, Testing-Eating Frequency, Calories Consumed, and Concentrated Sweets, were quantified from 24-hr recall interviews conducted with mother and child. Glycemic control was indexed by glycosylated hemoglobin (HA1C); lipid metabolism was indexed by fasting triglyceride levels (TRIG). The relationship of each adherence construct to metabolic control was tested separately. Patient age and disease duration served as exogenous variables in all models. Testing-Eating Frequency was associated with HA1C and Injection was associated with TRIG; in both cases better adherence was associated with better metabolic control. However, the standardized regression weights and variance accounted for were small. Patient age was a predictor of both adherence and metabolic control; older youngsters were less adherent and were in worse metabolic control. Inspection of models for younger versus older children suggested that age-homogeneous models improved prediction, but adherence and metabolic control linkages remained weak. Suggestions for refining the model are provided. PMID- 1432481 TI - Comparing social learning and family systems correlates of adaptation in youths with IDDM. AB - Evaluated social learning and family systems theoretical models to determine (a) whether illness-specific family relations (based on social learning theory) and general family behaviors (based on family systems theory) relate uniquely to the youths' illness-specific and psychosocial adaptation, and (b) whether these types of family relations covary or whether they represent distinct aspects of family functioning. Participants included 95 youths with insulin-dependent diabetes mellitus (IDDM) and their parents. Positive and supportive family relations (illness-specific family support, general family affection, general family adaptability) as well as conflictual and nonsupportive relations (i.e., illness specific family nonsupport, general family conflict) were assessed. Results suggest that both illness-specific and general family relations uniquely predict the youths' dietary adherence and general psychosocial adaptation. Because illness-specific and general family relations also covary, broad-based models that include both types of family functioning seem warranted. PMID- 1432482 TI - Stress, coping, and family functioning in the psychological adjustment of mothers of children and adolescents with cystic fibrosis. AB - Assessed the role of illness parameters, demographic parameters, and hypothesized psychosocial/mediational processes in the psychological adjustment of 68 mothers of children and adolescents (7-17 years of age) with cystic fibrosis. Together the illness and demographic parameters accounted for only 13-15% of the variance in maternal adjustment. However, the hypothesized mediational processes accounted for 35-40% increment in the variance in maternal adjustment. More specifically, maternal adjustment was associated with lower levels of perceived daily stress, less use of palliative coping methods, and family functioning characterized by high levels of supportiveness. PMID- 1432483 TI - Stress, appraisal, and coping in mothers of disabled and nondisabled children. AB - The cognitive-behavioral model of stress and coping provided the framework for this study of mothers of physically disabled children (n = 69) and mothers of nondisabled children (n = 63). The first aim was to test for differences between groups in responses to stressful parenting events. As hypothesized, mothers of disabled children reported higher levels of depressive symptomatology. Differences in psychological distress and health status approached significance. The second aim was to explore the mediating influences of coping strategies and cognitive appraisals. As predicted, emotion-focused coping was related to increased psychological distress in mothers of disabled children whereas problem focused coping was associated with decreased distress. Both relationships were significant even after controlling for differences in type of parenting stressor. Hierarchical regressions showed that 58 and 25% of the variance in psychological distress was explained by the independent variables; however, the predictors were different for the two groups of mothers. Factors that may explain the differential effectiveness of coping and appraisal, and clinical implications of this study are discussed. PMID- 1432484 TI - Social class and parenting children with mild and moderate mental retardation. AB - Based on Kohn's (1977) and Gecas' (1979) theories of social class and parenting values, the role of socioeconomic status (SES) as a determinant of parenting attitudes and behaviors and as a moderator of problems associated with raising children with handicaps was evaluated among 171 families raising a child with mild or moderate mental retardation. Self-report measures assessed mothers' and fathers' attitudes regarding control, independence, and closeness within the family, and parental and family problems. Supportive, aversive, and controlling parent-child interactions were observed in the home. As expected, higher SES was associated with parental attitudes and behaviors related to fostering independent initiative in the family, and lower SES parents exhibited relatively more controlling and negative behaviors. However, regardless of SES, controlling parental behaviors also were responsive to the level of functioning of the child with mental retardation. Consistent with an hypothesis about violations of SES related values, negative and controlling interactions with the child were more highly correlated with the parents' reports of parental and family problems for upper SES as opposed to lower SES parents. Several models of SES and family adaptation are discussed. PMID- 1432485 TI - Applying stigma theory to epilepsy: a test of a conceptual model. AB - Tested a theoretical model that sought to explain the association of stigma to self-esteem among adolescents with epilepsy. The model depicted hypothesized relationships among several characteristics of epilepsy (seizure type, seizure frequency, and duration of epilepsy), perceived stigma, management of disclosure, and self-esteem. Subjects were 64 adolescents 12 to 20 years old with idiopathic epilepsy. In a hierarchical multiple regression analysis, variables were entered into the equation in the order specified a priori by the model. Results showed that the data supported some hypotheses tested in the model: (a) Seizure type and seizure frequency predicted low self-esteem, and (b) the belief that epilepsy is stigmatizing predicted low self-esteem. However, several relationships of major theoretical significance were not realized. Explanations for why some aspects of stigma theory were not supported by the data are offered. PMID- 1432486 TI - Inhibitory effect of melanin on the interaction of Fonsecaea pedrosoi with mammalian cells in vitro. AB - Conidial forms of Fonsecaea pedrosoi, grown under conditions where melanin was or was not synthesized, were allowed to interact with normal and cytochalasin treated macrophages. Melanin-free conidia were more infective to the macrophages. Treatment of macrophages with either cytochalasin B or D before the interaction decreased, but did not totally prevent their infection by the fungi. This inhibitory effect was higher (approximately 90%) if F. pedrosoi was grown under conditions where melanin was not synthesized. When melanin-containing conidia were used, the inhibitory effect of the cytochalasin on the infection was lower (approximately 50%). At least two mechanisms of infection of the host cell were observed: typical phagocytosis and another process in which the fungi played a more active role. Infection by F.pedrosoi was also observed in the non professional phagocytic MDCK epithelial cell line. Two types of cytoplasmic vacuoles which contained parasites were seen in thin sections of host cells infected with F.pedrosoi: a 'tight' type and a 'loose' type. At least 200 conidia containing vacuoles were analysed by transmission electron microscopy. The 'tight' type was observed in 75% of the vacuoles of non-treated macrophages, suggesting an association with classical phagocytosis. On the other hand, the 'loose' type vacuole was seen in 75% of the vacuoles present in cytochalasin treated macrophages and seemed to be related to induced phagocytosis or active penetration by the fungi. PMID- 1432487 TI - Determination of plasma (1-->3)-beta-D-glucan: a new diagnostic aid to deep mycosis. AB - We present additional evidence that plasma from patients with deep-seated mycoses contains (1-->3)-beta-D-glucan. Digestion of such samples with endo-(1-->3)-beta D-glucanase completely abolished the ability of the plasma to activate factor-G, a horseshoe crab coagulation enzyme that is extremely sensitive to this polysaccharide. Measurement of plasma (1-->3)-beta-D-glucan is a promising method for the diagnosis of deep-seated mycoses and for monitoring the response of these infections to antifungal therapy. PMID- 1432488 TI - Immunoblotting analysis of sera from patients with candidal vaginitis and healthy females. AB - Antigenic components of Candida albicans were extracted from whole cells with a buffer containing SDS and 2-mercaptoethanol, and separated by SDS-polyacrylamide gel electrophoresis. The components reactive with IgG, IgA, IgM and IgE antibodies in sera from patients with (14 subjects) and without (15 subjects) C. albicans in the vagina, and from healthy females (34 subjects), were investigated by immunoblotting using immunoglobulin class-specific antibodies. Many components reacted with IgG and IgA in all sera tested; the major antigens that reacted strongly with the sera were 67, 62, 29 and 25 kDa components. Several components were observed which reacted with IgM in 63% of the sera; the 67, 62 and 25 kDa components that reacted with IgG and IgA also reacted with IgM. No components reacting with IgE were detected in any of the sera. No striking differences in antibody binding profiles to whole cell antigens were detected among the C. albicans positive and negative patients or the healthy subjects. On the other hand, IgG against extracellular proteinase was more frequently detected in the C. albicans positive patients than in the C. albicans negative group or the healthy subjects. This may suggest that vaginal infection with C. albicans contributes to a rise in anti-proteinase antibody levels. PMID- 1432489 TI - Microsporum gypseum complex in man and animals. AB - Twenty-eight strains of the Microsporum gypseum complex isolated from humans and animals were studied. The perfect form was found for 25 of the isolates. Nannizzia incurvata was the species most frequently involved in human pathology, while Nannizzia gypsea was most frequently found on animal lesions. Nannizzia fulva was rarely involved pathologically and Nannizzia corniculata was not isolated during this study. It is surprising to note that this species was not found even though most of our strains (22/28) came from Africa. Reliable methods are not available for differentiating among the anamorphs, which are commonly called M. gypseum, Microsporum fulvum or Microsporum boullardii. The Sabouraud medium conventionally used for medical mycology makes almost no distinction among them. We found that the species could be easily distinguished by colonial and microscopic features when grown on Takashio medium. When strains are atypical, sexual reproduction remains the reference technique but, in most cases, Takashio medium makes it possible to avoid this long drawn-out procedure. PMID- 1432490 TI - Cryptococcal peritonitis in a CAPD patient. AB - A 50-year-old diabetic woman with end-stage renal disease, who had been on continuous ambulatory peritoneal dialysis for 8 months, developed peritonitis caused by Cryptococcus neoformans var. neoformans. The patient was completely asymptomatic and infection was confirmed by detection of budding yeast cells in Gram-stained smears of turbid peritoneal fluid. The infection was cleared after intravenous fluconazole with delayed removal of the catheter. Fluconazole may be a suitable alternative drug in treating cryptococcal peritonitis. PMID- 1432491 TI - Activation of human complement system in paracoccidioidomycosis. AB - Plasma samples of 14 patients with paracoccidioidomycosis were analysed for components that represent activation of the complement system. Most patients (12/13) showed significant titres of complement-fixing antibodies and 14/14 had increased C4d/C4 ratios. There was no conclusive correlation between these two immunological indices, however. Factor B values of patients were similar to normal donors and fragment Ba was not detected in any of the patients. These results indicate a classical complement pathway activation in the plasma of patients with paracoccidioidomycosis. PMID- 1432492 TI - A microfermentation test for the rapid identification of yeasts. AB - The accuracy and speed of a microfermentation test (MFT), developed as a supplementary aid to other yeast identification systems, were compared with the conventional fermentation method in identifying 15 yeast species. The MFT significantly reduced the incubation period required to obtain a definitive identification. The method is easy to perform and the media and space requirements are minimal. PMID- 1432493 TI - Re-evaluation of the synonymy between Keratinomyces ceretanicus and Trichophyton ajelloi. AB - In 1987, Keratinomyces ceretanicus was reduced to synonymy with Trichophyton ajelloi based on mating between the putative ex-type culture, ATCC 58594, and minus mating strains of Arthroderma uncinatum. Although we confirm that ATCC 58594 produces fertile ascomata when mated with A. uncinatum, we demonstrate that this strain is not representative of the type of K. ceretanicus and conclude that K. ceretanicus should be maintained as a separate taxon. PMID- 1432494 TI - Burns associated with the use of microwave ovens. AB - This article reviews published reports of conventional and radiation burns associated with the use of microwave ovens. Conventional food burns can result from the ingestion of microwave heated food because consumers may overlook the differential temperature gradients within foods and between the food and the container. There are reports of accidental radiation injury associated with the use of microwave ovens, but they are difficult to evaluate because these reports lack definitive clinical data and verification of the actual radiation exposures. Only one study has provided useful insight into the clinical features of microwave radiation burns compared to conventional burns. PMID- 1432495 TI - Founder Samuel V. Abraham, MD--remembering his vision. PMID- 1432496 TI - Endophthalmitis following pediatric intraocular surgery for congenital cataracts and congenital glaucoma. AB - The incidence of endophthalmitis following pediatric anterior segment surgery is currently unknown. The paucity of reports of this entity has led some observers to recommend simultaneous bilateral surgery for congenital cataracts or glaucoma. In this study, we surveyed over 500 pediatric ophthalmologists and glaucoma specialists concerning their knowledge of, or involvement with, endophthalmitis following pediatric intraocular surgery. Seventeen cases of endophthalmitis were documented to occur out of 24,000 reported surgical cases. This results in an incidence estimate of 0.071%, or 7 cases per 10,000, which is similar to that recently reported following adult extracapsular cataract extraction. The presence of infection was diagnosed by the 3rd postoperative day in 82% of cases. An organism was documented by culture in 65% of cases. The organism was gram positive in all cases. Visual outcome was generally poor with 65% having no light perception. The presence of possible concurrent risk factors for postoperative endophthalmitis, including nasolacrimal duct obstruction and upper respiratory infection, was noted in 8 of the 17 cases. PMID- 1432497 TI - Congenital double elevator palsy: vertical saccadic velocity utilizing the scleral search coil technique. AB - Four patients with congenital double elevator palsy were studied who had clinically brisk elevation of the affected eye from downgaze to the midline position of rest, but severely limited or absent elevation above primary position. Forced duction tests were negative and Bell's phenomenon was present preoperatively in all patients. To clarify why upgaze saccades clinically seemed intact below but not above midline, vertical saccadic velocities were measured using the scleral search coil technique. The tracings of three cases suggest sufficient superior rectus function to generate a normal upward saccadic trajectory. A supranuclear lesion is the most likely etiology of the inability to elevate the eye well above primary position in these three patients. In a fourth patient, the reduced ability to elevate the affected eye above primary position is caused by a superior rectus paresis with decreased upward saccadic velocities. We suggest at least three distinct groups of patients present clinically as double elevator palsy: primary inferior rectus restriction, primary superior rectus paresis or palsy, and congenital supranuclear elevation deficiency. PMID- 1432498 TI - Surgery in the prism adaptation study: accuracy and dose response. Prism Adaptation Study Research Group. AB - Three hundred twenty-two patients underwent strabismus surgery for acquired esotropia according to a rigid protocol in the Prism Adaptation Study (PAS). This report describes the PAS surgical technique and the methods used to evaluate and assure adherence to the surgical protocol. We present analyses of the discrepancies between the amount of recession surgery planned by the surgeon and the amount of recession estimated by the masked graders from documentary photographs. In 74% of patients, the total discrepancy (combined from both medial rectus operations) was 1 mm or less. There was a distinct trend for masked graders to estimate larger recession amounts than were dictated by the protocol and claimed to be done by the surgeon. In 24% of patients, the masked graders estimated that the recession was more than 1 mm greater than that claimed by the surgeon, while in 2%, the graders estimated that the surgery was more than 1 mm less than planned. Of the 74 patients for whom the graders' estimated total recession was more than 1 mm greater than the amount planned by the surgeon, 88% were successful. Of the six patients for whom the graders' estimated total recession was more than 1 mm less than the amount planned by the surgeon, five (83%) were successful. We propose new surgical tables for patients with acquired esotropia. Enhanced amounts of recession appear to be necessary to decrease the rate of undercorrection for each group of patients. PMID- 1432499 TI - A mydriatic eye-drop combination without systemic effects for premature infants: a prospective double-blind study. AB - Eye drops used for diagnostic mydriasis may produce systemic side effects in preterm infants. Studies on the pupil dilating and systemic effect of various mydriatic agents yielded conflicting results. We conducted a prospective randomized double-blind study on the systemic effect of two mydriatic eye-drop combinations. Thirty-nine preterm infants were randomly assigned to two groups. An eye-drop combination of 2.5% phenylephrine and 0.5% tropicamide (group D) was compared with the combination of 0.5% cyclopentolate and 0.5% tropicamide (group F). Either eye-drop combination was followed by 0.5% tropicamide given 20 minutes later. Heart rate (HR) and the systolic, mean, and diastolic blood pressure (BP) were recorded before and after eye-drop instillation and after ophthalmoscopy. A control session with NaCl eye drops was added for each infant. A significant increase of BP and HR peak values was observed within 7 to 10 minutes after the cyclopentolate/tropicamide combination only. On the other hand, the mydriatic effect of the phenylephrine/tropicamide combination was significantly superior to that of the cyclopentolate/tropicamide combination. We recommend the combination of 2.5% phenylephrine and 0.5% tropicamide to achieve a sufficient diagnostic mydriasis without systemic side effects in preterm infants. PMID- 1432500 TI - Hypertropia following trochlear trauma. AB - Hypertropia following trauma to the trochlea is rare. The more widely recognized response of the trochlea to trauma is hypotropia or acquired Brown syndrome. We observed three cases of hypertropia following penetrating trauma to the trochlea. Each had computerized tomography and/or magnetic resonance imaging to assist in the understanding of the mechanism of the observed superior oblique dysfunction. The clinical course of these cases was variable. Awareness of the damaged trochlea's capacity to respond as a hypertropic as well as a hypotropic syndrome will allow for improved management of these unusual patients. PMID- 1432501 TI - Intraoperative succinylcholine and the postoperative eye alignment. AB - In 99 patients undergoing strabismus surgery, an intravenous bolus of succinylcholine (Sch) was given after completion of the strabismus procedure. Reliable data were obtained in 53 patients. The interlimbal distance measured at 60 seconds after injection (VR60) was compared to the interlimbal distance at 1 and 6 weeks postoperatively, to evaluate the correlation between the drug-induced eye position under anesthesia and the awake-eye alignment postoperatively. Correlations were highest in patients undergoing symmetric recessions of the medial or lateral recti in primary horizontal strabismus. Confidence intervals of 0.8 to 1.2 were noted for both the esotropia and exotropia groups. Two patients experienced Sch-related complications of masseter spasm and prolonged apnea. Although infrequent, the potential gravity of the complications from Sch use and the currently enjoyed high rate of success in primary strabismus surgery suggest that these formulas not be used clinically. Nonetheless, the high correlations between the drug-induced and awake ocular position provide further support to the premise that the Sch sensitive fibers provide an important motor component to the awake eye position. PMID- 1432502 TI - Ocular torsion-direct measurement with indirect ophthalmoscope and protractor. AB - Objective measurement of the optic nerve head (ONH)-foveal angle, representing the torsional status of 40 eyes in 20 normal patients, was performed by fundus photography and compared to a method utilizing an indirect ophthalmoscope and protractor described herein. Photography established a mean ONH-foveal angle of 7.03 degrees (SD 2.94 degrees). Comparison with the indirect/protractor method revealed a mean difference of 1.10 degrees (SD 0.99) with a range of 0 degrees to 4 degrees between methods. The indirect/protractor method seems to provide a rapid, inexpensive, and accurate method of determining the degree of ocular torsion when compared to the fundus photograph method which requires greater patient cooperation and investment in time and equipment. The ONH-foveal angle varies widely among normal individuals (0 degrees to 16 degrees). Variation between left and right eyes of the same individual was not significant (1.15 degrees, SD 1.39 degrees), and if greater than 4 degrees, probably represents cyclovertical muscle dysfunction or restrictive orbitopathy. The converse, however, may not always be true as individuals with less than 4 degrees difference between eyes may have cyclovertical muscle imbalance. PMID- 1432503 TI - Atropine cycloplegia: how many instillations does one need? AB - Atropine is accepted generally as the most efficient cycloplegic agent. Although it is considered a relatively safe drug, toxic local and systemic side effects do occur. The recommended regimen for atropine cycloplegia has been 7 to 10 applications within 3 to 4 days. We compared the cycloplegic effect of four instillations of atropine drops to the effect of eight instillations. The results showed that the cycloplegia obtained after eight instillations was not greater than after four instillations. PMID- 1432504 TI - Sclerocornea and interstitial deletion of the short arm of chromosome 6--(46XY del[6] [p22 p24]). AB - The interstitial deletion of the short arm of chromosome (6)--46 XY del (6) (p22.3 p24) is unrecorded. The ophthalmic findings in a dysmorphic infant included peripheral sclerocornea and epicanthal folds with upslanting palpebral fissures. We present a short review of sclerocornea and the ophthalmic findings of infants with anomalies of chromosome 6. Our findings provide further evidence that genes influencing the development of the anterior segment are located on the distal portion of the short arm of chromosome 6. PMID- 1432505 TI - Ocular findings of incontinentia pigmenti in a male infant with Klinefelter syndrome. AB - A male infant with Klinefelter karyotype (47, XXY) manifested both the typical dermatologic findings of the X-linked dominant disorder incontinentia pigmenti (Bloch-Sulzberger syndrome) and ocular findings including retinal pigmentary changes, peripheral retinal avascularity, and preretinal fibrovascular proliferation. To our knowledge, this is the first reported case of incontinentia pigmenti with this specific abnormal genotype manifesting ocular findings. PMID- 1432506 TI - Oculocutaneous albinism: variable expressivity of nystagmus in a sibship. AB - Traditionally, the diagnosis of ocular or oculocutaneous albinism (OCA) is based on a constellation of features including the presence of nystagmus associated with iris transillumination defects, hypopigmentation of the fundus, and hypoplasia of the fovea and optic nerve head. Nystagmus is the most frequent ocular sign for the ascertainment of albinism particularly in individuals who have lightly-pigmented parents. We report two siblings, a male and female, with minimal, if any, pigmentation of skin and hair, iris transillumination defects, blond fundi, and hypoplasia of the foveae and optic nerve heads who were discordant for nystagmus; the diagnosis of OCA was based on the clinical findings. These siblings presumably have the same genetic hypopigmentation defect and demonstrate that nystagmus is not a consistent finding in OCA and may not be an absolute criterion for diagnosis. PMID- 1432507 TI - Pseudo-slipped muscle due to perioperative inflammatory palsy. PMID- 1432508 TI - Corneal erosions and encephalopathy following exposure to "Rhino-Caps". PMID- 1432509 TI - Congenital ptosis. PMID- 1432510 TI - Samuel Victor Abraham, 1899-1992. PMID- 1432511 TI - Changes in eyelid position accompanying vertical rectus muscle surgery and prevention of lower lid retraction with adjustable surgery. AB - Whether or not eyelid position changes are caused by vertical rectus muscle surgery is controversial and poorly understood. We reviewed pre- and postoperative photographs of patients who underwent recession or resection of one or more vertical rectus muscles in a 10-year period. A change in eyelid position occurred frequently with vertical rectus muscle surgery. With superior rectus recession, 91% of the patients developed upper lid retraction. With inferior rectus recession, 94% of patients developed lower lid retraction. With inferior rectus resection, every patient developed lower lid advancement with accompanying flattening. We describe an adjustable surgical technique to prevent lower lid retraction associated with inferior rectus recession. The technique involves a separate adjustable suspension of the lower eyelid retractors from the inferior rectus insertion at the time of strabismus surgery. The lid position can then be adjusted separately at the time of muscle adjustment. After an average 2 1/2 month follow up, no statistically significant lid retraction could be measured in six patients who underwent the adjustable lid suspension, while statistically significant retraction (P < .01) developed in a group of nine patients who had inferior rectus recession alone. This technique did not limit the success of the strabismus surgery. PMID- 1432512 TI - Recognized scleral perforation during eye muscle surgery: incidence and sequelae. AB - Inadvertent perforation of the sclera is a widely recognized complication of eye muscle surgery. In the 1960s and 1970s, it was estimated to occur in 9% to 12% of patients operated. Fortunately, dreaded vision-threatening sequelae have been much less common. To better define the occurrence and sequelae of this complication, we sent a questionnaire to all 342 members of the American Association for Pediatric Ophthalmology and Strabismus. Scleral perforations, defined to include known retinal damage, occurred in 728 of nearly 554,000 eye muscle procedures performed by 223 surgeons. Perforations were two times more common with residents or fellows operating. They occurred not only during muscle reattachment (633 cases), but also during muscle disinsertion (24 cases), muscle dissection (6 cases), passage of traction sutures beneath the lateral rectus (5 cases), and preplacement of muscle sutures (5 cases). Many other perforations may have been unrecognized and uncounted. Visual loss was uncommon, occurring in only nine patients. Fourteen retinal detachments included four cases with partial and two with total loss of vision. Only three cases of endophthalmitis occurred, one resulting in partial visual loss and two in total visual loss. Techniques suggested by respondent surgeons to avoid perforations are discussed. PMID- 1432513 TI - The surgical treatment of traumatic Brown syndrome. AB - We present the results of surgical treatment in 13 patients who attended Moorfields Eye Hospital with traumatic Brown syndrome between 1975 and 1990. The average age was 34 years (range, 18 to 46 years), and in 12 cases the cause was a road traffic accident. Diplopia was the indication for surgery in all cases. Most patients had two surgical procedures; but in two patients, three were required. The outcome was assessed both subjectively and objectively. Objective assessment was by analysis of the preoperative and postoperative fields of binocular single vision and Hess charts which were available for 11 patients. The Hess charts were analyzed using a new scoring system. At final follow up, subjective improvement had occurred in 7 patients, 3 patients reported no improvement, and 3 patients thought their symptoms were worse. The field of binocular single vision improved in 8 patients and was worse in 3 patients. The Hess chart improved in 8 patients and was worse in 3 patients. The management of this difficult condition is discussed. PMID- 1432514 TI - Synthetic polypeptide sleeve for strabismus surgery. AB - A synthetic polypentapeptide sleeve was placed around the superior rectus muscle of five New Zealand white rabbits in hopes of preventing postoperative fibrous scarring. Two forms of the polypentapeptide were used. No significant inflammation or scarring occurred with either form of the polypentapeptide when compared to controls. One form elicited a fibrous membrane surrounding the sleeve within 2 weeks. The other elicited no such reaction after 2 months. The latter form of the polypentapeptide may be useful in preventing scarring following strabismus surgery. PMID- 1432515 TI - Hypertensive retinopathy: a cause of decreased visual acuity in children. AB - Hypertensive retinopathy may present atypically in children. Delays in diagnosis may result in permanent visual loss, as demonstrated in three cases we saw. PMID- 1432516 TI - Levodopa and childhood amblyopia. AB - A pilot study was undertaken to address the tolerance and efficacy of levodopa/carbidopa treatment for amblyopia in older amblyopic children who failed to respond to conventional occlusion therapy. Five amblyopic children, between the ages of 7 and 12 years, and two normal adults were given between 100 mg/25 mg and 400 mg/100 mg of levodopa/carbidopa, respectively, depending on body weight. A symptoms questionnaire was completed, with temperature, respiration, heart rate, and blood pressure taken periodically to assess tolerance. Blood samples were taken, via a heparin well, to assess the pharmacokinetics of levodopa, dopamine, noradrenaline, and DOPAC. Snellen visual acuity, contrast sensitivity, stereo acuity, and pattern VERs were measured periodically to assess efficacy. The results revealed a high prevalence of side effects including emesis and nausea (four of seven subjects). Pharmacokinetics revealed that maximum serum levels of levodopa occurred 30 minutes to 1 hour after drug ingestion and decreased by 50% after 2 to 4 hours. One hour after drug ingestion, Snellen visual acuity temporarily improved from an average of 20/159 to 20/83 in the amblyopic eyes. Contrast sensitivity and pattern VERs (10-minute checks) temporarily improved in both dominant and amblyopic eyes, whereas visual function remained stable in normal eyes. The improvements in visual function started to decrease 5 hours after drug ingestion. The results are discussed in the context of developing a therapeutic trial of levodopa/carbidopa for childhood amblyopia. PMID- 1432517 TI - Refractive error changes following strabismus surgery. AB - Several uncontrolled, retrospective studies have suggested that permanent changes in refractive error can be seen following strabismus surgery. We prospectively enrolled 68 patients undergoing strabismus surgery for evaluation of pre- and postoperative cycloplegic refraction. In addition, the adult patients had computerized corneal topography recorded using the Corneal Modeling System, (Computed Anatomy, Inc, New York, NY). Pre- and postoperative refractions were compared using spherical equivalent and meridional equivalent (90- and 180-degree meridian). We found no significant change in the spherical equivalent between the pre- and postoperative measurements. However, a significant increase in the astigmatic power at 180 degrees (meridional equivalent at 180 degrees) was detected in both pediatric and adult patients. We did not observe any qualitative change in the corneal topography pre- and postoperatively. The change in astigmatic power at 180 degrees is equivalent to additional plus-cylinder correction at 90 degrees and was persistent throughout the 4-month postoperative period. PMID- 1432518 TI - Visual hand display (VHD) as an introductory procedure for measuring vision in infants and young children with visual impairment. AB - We developed the Visual Hand Display (VHD) to measure vision in visually impaired infants and young children. The VHD is a circular fabric mitten, which is held easily by inserting the hand between the two surfaces. Black-and-white stripes are attached to one surface, 25, 15, 10, 4, and 2 mm per stripe. The VHD acuity is determined by the shortest test distance and the smallest stripes that the patient can detect. The VHD acuities were compared with preferential looking (PL) staircase acuities in 130 patients (53 males, 77 females; age range, 2 to 13 years; median, 21.0 months). Of these, 107 (82.3%) had various degrees of retinopathy of prematurity. The correlation between the VHD and the PL acuities was high (R2 = 0.849). PL acuities were better than the VHD acuities in 98/130 patients (75.4%), with an average difference of 0.51 (SD = 0.70) octave. The visual acuity differences were more pronounced in subjects with slight visual impairment and much less in subjects with severe visual impairment. The VHD seems to be an effective introductory method to evaluate visual acuity in severely visually impaired infants and young children. This method also would be effective with severely mentally and physically disabled patients who cannot undergo PL testing. PMID- 1432520 TI - Stage I intraoperative adjustment of eye muscle surgery under general anesthesia. PMID- 1432519 TI - Frosted branch angiitis: the role of systemic corticosteroids. PMID- 1432521 TI - A technique for removing thorns from the cornea. PMID- 1432522 TI - Use of the laser pointer in facilitating measurement of visual acuity in young children. PMID- 1432523 TI - Is the phakic eye normal in monocular pediatric aphakia? AB - This retrospective review of 97 pediatric patients who underwent monocular surgery for congenital or developmental cataracts studied the incidence of abnormalities in the contralateral phakic eye. Fifty-nine percent of patients had a normal phakic eye. However, 40 patients showed at least one abnormality in the phakic eye: reduced vision (21%), nystagmus (19%), cataract (15%), iris heterochromia (9%), myopia (6%), microphthalmos (6%), pupillary miosis (2%), congenital glaucoma (2%), optic nerve abnormality (2%), aniridia (1%), and corneal opacity (1%). Not all abnormalities were detected at the time of diagnosis of the contralateral cataract. The more significant findings of reduced vision and nystagmus in the phakic eye were usually detected postoperatively, often several months after the optimum time for treatment of pediatric cataracts. We suggest that monocular cataract surgery not be delayed. This will allow the best vision to be obtained for the aphakic eye, as the "sound eye" may not always be normal in monocular pediatric aphakia. PMID- 1432524 TI - An evaluation of abdominal staging procedures performed in pediatric patients with advanced Hodgkin's disease: a report from the Childrens Cancer Study Group. AB - Forty-nine children and adolescents underwent staging laparotomy in the course of a cooperative group (CCG) study of advanced Hodgkin's disease (HD). The purpose of the study was to evaluate the toxicity of a regimen of 12 cycles of doxorubicin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) plus 2,100 cGy regional irradiation in patients with stage III-IV disease. Review of the biopsies and specimens from these 49 laparotomies identified distinct patterns of abdominal involvement and permitted an evaluation of the importance of different aspects of the staging procedure and an assessment of the value of non-invasive techniques in determining the extent of abdominal disease. The major observations from these studies were: (1) computed tomography (CT) and gallium 67 scans (GA) were specific (few false positives), but not sensitive, indicators of abdominal disease; (2) negative findings at laparotomy in 29 patients permitted a contraction of the abdominal radiation fields with no subsequent abdominal recurrence in these patients; (3) in five patients, stage IV status was established only by laparotomy and open hepatic biopsy; (4) all patients with lower abdominal or pelvic involvement also had upper abdominal node or splenic involvement; (5) involvement of splenic hilar nodes was a sensitive predictor of splenic involvement; (6) disease in the inferior paraaortic nodes accurately predicted the presence of more distal disease, ie, in the iliac or pelvic node groups; and (7) in a limited experience, transposition of the ovaries protected ovarian function from the effects of pelvic irradiation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432525 TI - Broviac central venous catheters inserted via the saphenous or femoral vein in the NICU under local anesthesia. AB - We present our experience with 92 Broviac central venous catheters inserted into 84 infants over a 31-month period. Our technique specifies placement in the neonatal intensive care unit under local anesthesia, with insertion to the inferior vena caval-atrial junction via the saphenous or femoral vein, with a subcutaneous tunnel to an exist site on the anterior thigh. We conclude this technique to be safe, efficient, convenient, cost-effective, and minimally uncomfortable to the infant, with no increase in morbidity or mortality in comparison to previously described methods. PMID- 1432526 TI - Proximal and distal cannulation of the internal jugular vein for ECMO in a primate. AB - Extracorporeal membrane oxygenation (ECMO) is lifesaving for infants with severe respiratory distress but is complicated by severe intracranial hemorrhage in 10% to 30% of patients. Intracranial venous hypertension, as a result of ligation of the internal jugular vein (IJV), has been hypothesized as a contributing factor to cerebral edema and subsequent hemorrhage. Accessory cephalad IJV cannulation may serve as a means of additional venous drainage to the pump as well as protection against intracranial venous hypertension. Proximal and distal cannulation of the IJV were studied in a primate model. The parameters monitored included sagittal sinus, right and left ventricular pressures as well as venous pressure in the ECMO circuit. The cephalad venous cannula was clamped and unclamped at 30-minute intervals. There was no significant difference in sagittal sinus or intracranial pressures during periods of cephalad cannula clamping or unclamping. Venous return was augmented when the cephalad cannula was unclamped. Cephalad cannulation has no demonstrable protective effect on intracranial, subarachnoid or venous pressures but does improve venous return to the ECMO circuit. It is concluded that cephalad venous cannulation is not necessary in all cases and should be reserved for those patients requiring additional venous drainage to support pump flow. PMID- 1432527 TI - Congenital diaphragmatic hernia in an era of delayed repair after medical and/or extracorporeal membrane oxygenation stabilization: a prognostic and management classification. AB - In November 1987 we began to practice delayed repair of acutely symptomatic congenital diaphragmatic hernia (CDH) following medical and/or extracorporeal membrane oxygenation (ECMO) stabilization. We reviewed 23 consecutive patients with CDH symptomatic at birth treated over the ensuing 2 1/2 years. The mean age at admission, age at repair, and interval from admission to repair were 4.9, 37.0, and 32.6 hours, respectively. Overall survival was 52% (12/23). ECMO was used in 14 patients with 7 survivors (50%); 4 of these patients underwent repair prior to ECMO and 10 while on ECMO. The patients were retrospectively grouped into three classes based on postductal arterial blood gas (ABG) response to conventional medical management: class A (n = 8), able to achieve and sustain adequate oxygenation (PO2 greater than 60 mm Hg) and hyperventilation (PCO2 less than 40 mm Hg); class B (n = 10), unable to sustain adequate oxygenation (PO2 less than 60 mm Hg) but able to be hyperventilated (PCO2 less than 40 mm Hg); and class C (n = 5), unable to be oxygenated (PO2 less than 60 mm Hg) or hyperventilated (PCO2 greater than 40 mm Hg). The interval from admission to repair was 13.6, 53.5, and 25.4 hours for classes A, B, and C, respectively. Two class A (25%), nine class B (90%), and three class C patients (60%) were placed on ECMO. Survival rates were 88%, 50%, and 0% for classes A, B, and C, respectively. We propose the following management protocol. Class A patients are stable and can be repaired at any convenient point after admission without prerepair ECMO; few will need it afterward.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432528 TI - Major surgical intervention during extracorporeal membrane oxygenation. AB - Of 135 patients treated with extracorporeal membrane oxygenation (ECMO) between January 1987 and December 1989, 19 (14.0%) patients underwent surgical procedures while on ECMO. Thirteen (68%) patients had operations related to hemorrhage, including cannula site (6), mediastinal (1), hemoperitoneum (3), and hemothorax (3). Six of 13 patients required repetitive operations for bleeding; 4 of 6 died. Six (35%) patients had operations for congenital pathology including patent ductus (PDA) ligation (2), repair of transposition of the great vessels (2), repair of coarctation (1), and repair of congenital diaphragmatic hernia (3). One patient had multiple simultaneous procedures performed. Of these 6 patients, 4 were decannulated immediately and 2 were decannulated within 28 hours following surgery without any bleeding complications. Fifteen of 19 patients were operated on in the neonatal intensive care unit. The 4 remaining patients required transport on ECMO to the surgical suite. Thirteen of the 19 patients requiring surgical intervention on ECMO survived. In the 13 survivors, the mean time to decannulation postoperative was 45 hours, and in those that died it was 90 hours. Our experience suggests that surgical intervention while on ECMO is technically feasible with the best results achieved when rapid discontinuation of ECMO can be accomplished postoperatively. Due to this fact major surgical intervention should be postponed if possible until near the conclusion of the ECMO therapy. PMID- 1432529 TI - Elevated levels of endotoxin, oxygen-derived free radicals, and cytokines during extracorporeal membrane oxygenation. AB - It has been demonstrated that the initiation of extracorporeal membrane oxygenation (ECMO) is associated with an increase in the circulating plasma levels of inflammatory mediators. We have expanded the study of these substances to include measurements of complement activation, prostaglandin production, endotoxin appearance, oxygen-derived free radical generation, and cytokine release before, during, and after ECMO. A reproducible second phase of complement activity and prostaglandin synthesis was associated with the appearance of detectable circulating endotoxin (0.04 U/mL pre-ECMO to 0.07 U/mL at 36 hours, P less than .05). Oxygen-derived free radical activity also increased (2 ng/mL to 3 ng/mL at 36 hours, P less than .05), as did plasma levels of tumor necrosis factor (40 pg/mL to 70 pg/mL at 36 hours, nonsurvivor group: P less than .05). Interleukin-1 was elevated above normal, but there were no significant variations noted during the time period studied. Small amounts of interleukin-6 were also detected in the occasional patient. None of these mediators differed significantly between survivors and nonsurvivors. These data indicate that ECMO is associated with a previously undescribed, endotoxin-related, generalized inflammatory state after 36 hours of support. The pulmonary, renal, and cardiac dysfunctions documented with prolonged bypass can all be related to a classic sepsis syndrome. PMID- 1432530 TI - Biliovenous fistula in children after blunt liver trauma: proposal for a simple surgical treatment. AB - Biliovenous fistula (BVF) with subsequent leakage of bile into the venous system is a rare but serious complication of blunt liver trauma. Nine cases have been reported since 1975. Surgical therapy is indicated; however, there are still controversies as to which operative method should be applied. Based on experience gained in adult surgery, resection of the BVF together with necrotic liver tissue is also recommended in children. We describe both an organ-saving and technically simple method that was applied in two male patients, 2 and 10 years old, respectively, suffering from BVF. After debridement and tamponade of a necrotic cavity of the liver, drainage was carried out. This prevented bilious leak into the venous system. Based on the case history of these two patients, management of BVF fistula will be described. Pathophysiology of bilhemia and the drainage effect will be discussed in light of a review of the literature. PMID- 1432531 TI - Splenic autotransplantation provides protection against fatal sepsis in young but not in old rats. AB - Splenectomy increases the risk of contracting infections with high mortality. Thus, splenic tissue should be repaired orthotopically whenever possible. If all attempts fail, splenic autotransplantation might be a suitable method for splenic salvage. The protective function of such transplants in adults has been questioned, leading to a decreased frequency of splenic autotransplantations. However, the regeneration of splenic tissue is better in the young organism than in the old, suggesting that the protection provided by regenerated splenic tissue might be more reliable in children than in adults. In addition, children are at a higher risk in the case of overwhelming postsplenectomy sepsis. The protection warranted by regenerated splenic tissue after autotransplantation at different ages was examined using a highly standardized animal model. Sham operation, splenectomy, and splenic autotransplantation were performed on adult, weanling, and newborn rats, and Streptococcus pneumoniae was applied intranasally 9 months after the operation. After pneumococcal challenge about 80% of the splenectomized animals in the different age groups died of infection, whereas only 20% of the sham operated rats died. Regenerated splenic tissue resulting from splenic autotransplantation performed on adult or weanling rats demonstrated no protective function. However, in newborn rats with transplanted splenic tissue, both survival rate and survival time were increased significantly. Determination of lymphocyte subsets in the blood did not allow the protective role of splenic transplants to be predicted. This study indicates that disappointing results of splenic autotransplantation in adult patients should not lead to false pessimism about the role of this operation in children. PMID- 1432532 TI - Correlation between extrinsic nerve fibers and synapses in the muscle layers of bowels affected by Hirschsprung's disease. AB - The aim of this study is to clarify any correlation between nerve terminals (synapses) and proliferating extrinsic nerve fibers in the muscle layers of bowels affected by Hirschsprung's disease (HD). Synapses and extrinsic nerve fibers in the muscle layers of bowels of 10 patients with HD and 8 comparable controls were labeled with monoclonal antibody (MAb) 171B5 and acetylcholinesterase (AChE), respectively. In the control a rich and even distribution of synapses, representing neuromuscular junctions, was seen in the muscle layers, together with dense clusters of synapses in the adjacent myenteric plexuses; proliferation of extrinsic nerve fibers was not seen. In the transitional oligoganglionic segment of HD, many synapses were present in the myenteric plexus, but a few synapses in the muscle layers; there was a gradual increase of extrinsic nerve fibers from proximal to distal. In the narrow aganglionic segment very few synapses were seen in the muscle layers; proliferating nerve fibers and bundles were prominent. We conclude that the muscle layers of bowels affected by HD were almost denervated despite presence of intrinsic nervous elements in the oligoganglionic segment and proliferating extrinsic nerve fibers in the aganglionic segment. PMID- 1432533 TI - Meconium ileus-like condition in Chinese neonates. AB - Between January 1985 and May 1990, 16 neonates were treated for meconium ileus (MI) at this hospital. All babies were born to Chinese couples. Seven of them were premature, but none of them weighed less than 1,000 g. Eight patients underwent operations either because of mistaken diagnosis, as ileal atresia or long-segment Hirschsprung's disease, or because of complicated MI, including two meconium peritonitis and one associated with ileal atresia. Gastrograffin enema was successful in management of eight uncomplicated MI. The albumin content in the meconium of the last nine cases, including four complicated cases, ranged from 9.2 to 93.3 mg/g dry meconium. Usually, albumin is not present in normal meconium. All cases received sweat test, which were negative. Three patients died in the follow-up period. Sepsis of unknown origin, multiple congenital anomalies, and severe metabolic problems were the causes of death. The other 13 patients are doing well. They have exhibited no pulmonary or digestive problems during their follow-up period, which ranged from 11 months to 5 years. They are healthy and receive regular diets. Growth and development are appropriate for their age groups. PMID- 1432534 TI - Colonoscopic polypectomy in children. AB - Between January 1984 and July 1990, a total of 129 colonoscopic snare polypectomies were performed during 77 sessions on 74 patients aged 2 to 12 years. Bleeding per rectum (mean duration, 10 months) was the chief presenting symptom and was present in all of these patients. In 89% of patients polypectomy was carried out without using general anesthesia. Ninety-six percent of patients had juvenile polyps. Two patients had familial polyposis coli and one patient had a solitary adenomatous polyp. The majority (98; 80%) of the polyps were located in the rectosigmoid region. Four patients developed complications, one needing emergency operation. There were no deaths in the series. It is concluded that colonoscopic snare polypectomy is a simple, effective, and safe procedure for treating colorectal polyps in children. PMID- 1432535 TI - Tracheoesophageal fistula associated with perforated Meckel's diverticulum. AB - Neonates with esophageal atresia and tracheoesophageal fistula (TEF) may present with respiratory distress. Intubation and mechanical ventilation may force air from the tracheobronchial tree, through a distal fistula and into the gastrointestinal tract. We present a newborn with TEF who became moribund during mechanical ventilation. High ventilator pressures transmitted via the TEF caused over distention of the gastrointestinal tract and perforation of a Meckel's diverticulum. PMID- 1432536 TI - Congenital diaphragmatic hernia presenting due to gastrointestinal complications. AB - Congenital diaphragmatic hernia (CDH) presents beyond the first hours of life in 10% to 20% of cases. Presenting symptoms may be quite nonspecific, and are often gastrointestinal rather than respiratory in origin. We have recently had experience with five such cases, one in a newborn and four in older children. All presented with symptoms related to gastrointestinal complications of their diaphragmatic defect. In the newborn, gastric perforation had occurred, a complication of this anomaly not previously reported. The chest radiograph showed loops of bowel in the chest in all cases, allowing correct preoperative diagnoses. Urgent operative intervention was undertaken in each case with good results and no long-term morbidity. The risk of intestinal strangulation in the late-presenting CDH patient warrants emergent surgical management, which should be rewarded by uniform survival with few complications. Although preoperative stabilization may decrease the severity of pulmonary vasospasm in the newborn with respiratory failure, delay may increase the risk of bowel infarction in the older child presenting with gastrointestinal symptoms. PMID- 1432537 TI - Granulomatous peritonitis by ascaris. AB - The granulomatous peritonitis by ascaris (GPA) is a rare complication of intestinal ascariasis due to the perforation of the digestive tract by the adult worm, which deposits its ova in free peritoneum; therefore, provoking an intense granulomatous inflammatory reaction. We report a case of an 8-year-old boy with GPA, emphasizing the clinical and diagnostical aspects and the therapeutics procedures. PMID- 1432538 TI - Retroperitoneal alimentary tract duplications detected in utero. AB - The prenatal diagnosis of numerous congenital anomalies has become routine. The prenatal diagnosis of cystic lesions of the retroperitoneum can be due to a variety of renal, gastrointestinal, or adrenal lesions. This finding demands aggressive postnatal follow-up to rule out the possibility of cystic adrenal neuroblastoma. We report the first cases of retroperitoneal cystic masses diagnosed in utero that ultimately proved to be enteric duplications. Therefore, the differential diagnosis of cystic masses of the retroperitoneum found prenatally should be expanded to include enteric duplication cysts. PMID- 1432539 TI - Intussusception and intestinal perforations caused by multiple trichobezoars. PMID- 1432540 TI - Necrosis of the ileum in a diabetic adolescent. AB - A 17-year-old boy with insulin-dependent diabetes mellitus developed ketoacidosis and transitory shock. After resolution of his metabolic imbalance, he developed an acute abdomen prompting exploratory surgery. A section of necrotic ileum was found and resected. PMID- 1432541 TI - Tubular duplication of the hindgut with genitourinary anomalies. AB - Hindgut duplication including the colon and rectum as well as the genital and urinary organs are extremely rare. Only a few cases are noted in the medical literature. In this report, a newborn with exstrophy of the urinary bladder, double vagina and uterus, double anus, and complete duplication of rectum and colon with malrotation is presented. PMID- 1432542 TI - Single-system cecoureterocele. AB - A rare case of single system cecoureterocele associated with ipsilateral dysplastic kidney in a 4-year-old girl is reported. The preoperative radiological and endoscopic investigations identified ureterocele but not its cecal extension. The latter was diagnosed only during the transvesical surgery. Complete cure of her symptoms was achieved following staged procedures comprising of right ipsilateral nephroureterectomy followed by combined transvesical and transurethral deroofing of the cecoureterocele, excision of ureteric stump and its extension in the bladder and repair of the detrusor. This is the second case report in English language literature of single-system cecoureterocele. PMID- 1432543 TI - Removal of a multicystic half of a horseshoe kidney: significance of preoperative evaluation in identifying abnormal surgical anatomy. AB - A rare case of multicystic dysplasia in half of a horseshoe kidney is presented. Proper evaluation led to a modified surgical approach necessary for adequate exposure, division of the isthmus, and removal of the diseased component. Considerations applicable to the treatment of multicystic dysplasia and renal fusion are discussed. The surgical anatomy of horseshoe kidney is reviewed. PMID- 1432544 TI - Case of a testis prolapsed through a skin defect in the upper scrotum. PMID- 1432545 TI - Lymphatic vessel dysplasias. PMID- 1432547 TI - Diagnosing inguinal hernia. PMID- 1432546 TI - Muscle-sparing lateral thoracotomy has much to recommend it in neonates. PMID- 1432548 TI - Congenital lumbar hernia. PMID- 1432549 TI - Prepregnancy care and prevention of birth defects. AB - Birth defects and disturbances in growth and development need an increasing attention in perinatal medicine. It is remarkable that so little attention has been paid to the pathogenesis of malformations in the literature in an approach to find aspects of prevention. Primary prevention of birth defects is an important public health issue as malformations have important consequences both for society and the individuals concerned. Prepregnancy care as a logical precursor to antenatal care, offers risk-assessment, advice and occasionally treatment before pregnancy, in order to avoid congenital malformations. It is therefore that we started a research program with emphasis on primary prevention of congenital malformations. In this respect medication, maternal nutritional status, diabetes mellitus and neural tube defects are discussed. PMID- 1432550 TI - Vibro-acoustic stimulation in high-risk pregnancies; maternal perception of fetal movements, fetal heart rate and fetal outcome. AB - Maternal perception of fetal movement in response to vibro-acoustic stimulation was compared with antenatal fetal heart rate monitoring as a test of fetal well being in a population of gravidae with high-risk pregnancies (n = 517), admitted to the high-risk ward at Danderyd Hospital, Karolinska Institutet; a total of 2,015 tests were performed. The sensitivity and the specificity of the test compared to the fetal heart rate tracing was 81% and 89% respectively. If the test was performed within 24 hours of delivery, its predictive value for fetal asphyxia (i.e. a 5-minute Apgar score < 7) was 14% (7/49). Ten per cent of the patients felt no fetal movement in response to stimulation (irrespective of gestational age). In five cases where fetal heart rate tracings were pathological, stimulation nonetheless produced fetal movement and fetal outcome was good. Pathological heart rate tracings and no fetal movement in response to stimulation were present in 30 cases (out of 251 with no fetal movements at stimulation), in seven of which the infants had 5-minute Apgar scores < 7. Although many patients underwent repeated vibro-acoustic stimulation, there was no evidence of fetal habituation to the test. On 24 occasions (i.e. 1.2%), the patient denied vibro-acoustic stimulation, mostly because of previous discomfort due to vigorous fetal response. Where resources are limited, maternal perception of fetal movements in response to vibro-acoustic stimulation might be a useful alternative for preliminary screening of high-risk pregnancies. PMID- 1432551 TI - Acoustic stimulation as a diagnostic test: comparison with oxytocin challenge test. AB - The usefulness of an acoustic stimulation test as a marker of fetal well-being was evaluated in a randomized controlled study of 121 pregnant women exhibiting a non-reactive fetal non-stress test at term. The women were randomly divided into two groups; those in the first group (n = 62) underwent an acoustic stimulation test immediately prior to an oxytocin challenge test, while those in the second (n = 59) underwent an oxytocin challenge test only. Fetal response to the acoustic stimulation was non-reactive in 22.5% of the women tested in the first group. The incidence of abnormal oxytocin challenge test among the women who were previously subjected to an acoustic stimulation was somewhat lower than among those who did not (14.5% vs. 23.7%), but the difference was not significant. In the prediction of an abnormal oxytocin challenge test, a non-reactive acoustic stimulation test had a sensitivity of 100%, a positive predictive value of 64% and a specificity of 91%. As a single test for the prediction of fetal distress in labor (n = 62), the acoustic stimulation test had a specificity and a positive predictive value similar to those of the oxytocin challenge test (n = 121), and its sensitivity was even higher (88% vs. 71%). We conclude that the acoustic stimulation test is at least as reliable as the oxytocin challenge test in the evaluation of fetal well-being in women exhibiting a non-reactive non-stress test at term. PMID- 1432552 TI - Disseminated herpes simplex infection in a twin: the role of the "stat" autopsy in immediate therapeutic intervention for survival of multiple birth neonates. AB - Multiple birth neonates are unique in sharing similar intrauterine, and commonly the extrauterine, environments. The development of an infectious disease in one infant during the perinatal period assumes special significance in this setting, and the other siblings are often at high risk for a similar disease. Under these circumstances it is important to make a rapid etiologic diagnosis to provide appropriate therapeutic intervention. The immediate, or "stat", autopsy is a diagnostic modality involving the use of multiple procedures for the rapid diagnosis of perinatal infection which may be lifesaving in the setting of multiple birth neonates. This report describes the use of the "stat" autopsy to diagnose a fatal case of disseminated herpes simplex infection in a twin, which lead to the immediate treatment of the surviving sibling with appropriate antiviral medication. PMID- 1432553 TI - The effect of prenatal administration of dexamethasone and ritodrine on cord blood cortisol and glucose concentrations in premature infants with respiratory distress syndrome. AB - The influence of maternal dexamethasone and ritodrine administration during pregnancy on cord blood cortisol and capillary serum glucose concentrations and on the incidence of respiratory distress syndrome (RDS) was studied in 30 premature infants (gestational age 27-36 weeks), and compared with a matched control group of 37 premature infants where no such medications were administered. RDS occurred less often in the treated group of infants (13.3%) than in the controls (35.1%, p < 0.01). The healthy treated infants had a significantly lower mean umbilical cord plasma cortisol concentration (5.5 +/- 1.8 ug/dl, mean +/- SD) than that observed in the controls (11.2 +/- 3.9 ug/dl, p < 0.01). Mean cord plasma cortisol concentrations increased with duration of pregnancy. No significant difference in the capillary serum glucose at 30 minutes post-delivery was found between the healthy, RDS, treated and non-treated infants. No adverse effects of steroid and ritodrine therapy were observed. PMID- 1432554 TI - Oro-naso-pharyngeal suction at birth: effects on respiratory adaptation of normal term vaginally born infants. AB - The effect of oro-naso-pharyngeal suction at birth on pulmonary mechanics is described in a random assigned controlled study of 40 normal term vaginally born infants. Twenty cases had their oro-naso-pharynx suctioned immediately after birth (S Group), whereas 20 were not suctioned in the neonatal period (NS Group). A computerized pneumotachographic system (MECVENT) was used for the assessment of respiratory mechanics (Dynamic Compliance (C. Dyn.) and Total Pulmonary Resistance (R) in inspiration and expiration at 10, 30 and 120 minutes after birth. In both groups the C. Dyn increased during the study period whereas the R decreased, mainly in the initial 30 minutes. No significant differences were observed between S and NS groups for any of the parameters of respiratory mechanics. The results obtained in this study provide no physiological basis to recommend routine airway suction at birth in normal, term, vaginally born infants. PMID- 1432555 TI - Umbilical artery blood flow velocity waveforms in twin pregnancies. AB - To detect discordant fetal growth in twin pregnancies and assess a possible role for Doppler ultrasound measurements of blood flow velocity waveforms in umbilical arteries in such cases, 32 twin pregnancies were examined on 125 occasions. The last examination was within 14 days of delivery. There was postpartum death of one pair of twins with the twin transfusion syndrome. Birthweight was appropriate for gestational age in 15 twin pairs, both infants were small for gestational age (SGA) in 5, and one of the infants was SGA in 12 twin pairs. The correlation coefficient of RI difference at the last examination and percentage birth weight difference in twin pairs was 0.68. Cutoff points for the delta RI and weight difference were established. The sensitivity of delta RI (0.1) was 77.8%; specificity, 95.8%; positive predictive value, 87.5%; and negative predictive value, 92.0%. PMID- 1432556 TI - Severe localised pulmonary interstitial emphysema--decompression by selective bronchial intubation. AB - We report three infants (26-28 weeks gestational age) in whom selective bronchial intubation was associated with successful decompression of severe localised pulmonary interstitial emphysema, uniquely in two cases this involved intubation of the left main bronchus. Pulmonary interstitial emphysema did not recur despite maintenance of selective intubation for only 48 hours or less in all three cases. PMID- 1432557 TI - Intestinal obstruction and perforation following sucralfate administration in a very low birth weight infant. AB - A case of intestinal obstruction and perforation following sucralfate administration in a very low birth weight infant is reported. Potential adverse effects of using sucralfate for prophylaxis of stress ulcer in premature babies are discussed. PMID- 1432558 TI - Reliability and validity of the Coolidge Axis II Inventory: a new inventory for the assessment of personality disorders. AB - This group of studies describes the development of a 200 item, self-report, 4 point true-false inventory (Coolidge Axis II Inventory [CATI]) to assess personality disorders according to the criteria established in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-III-R]; American Psychiatric Association, 1987). The 13 personality disorder scales of the CATI had a mean test-retest reliability of .90 and a median internal consistency (Cronbach's alpha) of .76. There was a 50% concordance rate with clinician's diagnosis for 24 personality disordered patients. The median concurrent validity (raw score sums) between the CATI and the Millon Clinical Multiaxial Inventory-II for the 13 personality disorder scales was .58. Preliminary studies also support the reliability and validity of Depression, Anxiety, and Brain Dysfunction scales. PMID- 1432559 TI - Classification of adult attachment: an integrative taxonomy from attachment and psychoanalytic theories. AB - Developmental and psychoanalytic theorists have focused increasingly on empirically determined early childhood antecedents of adult attachments, with several resulting taxonomic models. This article suggests a theoretically based and clinically based model of attachment consistent with both psychoanalytic and attachment theories, resulting in an integrative taxonomy of four adult attachment styles: dependent, avoidant, hostile, and resistant-ambivalent. These styles reflect behavioral manifestations of dependence and anger, as derived from the interaction of primitive relational drives, defenses, and interpersonal experience. In addition to theoretical construction, brief clinical examples are presented to facilitate discussion of the model. PMID- 1432560 TI - The evaluation of truthfulness in alleged sex offenders' self-reports: 16PF and MMPI validity scales. AB - The evaluation of response bias (i.e., minimization or exaggeration) is central to forensic psychological evaluations. Yet few studies have assessed forensic samples to investigate the ability of psychological tests to detect response bias. We studied the relationship between the Sixteen Personality Factors Questionnaire (16PF) and the Minnesota Multiphasic Personality Inventory (MMPI) validity scales for 65 alleged sex offenders and assessed the effects of different cutoff scores for the 16PF validity scales. Results indicate consistent significant correlations between the validity scales of the 16PF and the MMPI for measures of minimization and exaggeration. use of a priori cutoff scores resulted in the classification of our sample in proportions parallel to those found in previous research for the 16PF Fake-Good scale but not the Fake-Bad scale. Our results indicate that 16PF validity scales are useful, but interpretations must take into account different base rates of response bias between sex offenders and the general population. PMID- 1432561 TI - The Rorschach test for predicting suicide among depressed adolescent inpatients. AB - With the decreasing length of psychiatric hospitalizations, identification of test indicators of suicide risk becomes critically important. This Rorschach study was designed to model a clinical decision-making scenario concerning adolescent suicide risk. Using Psychiatric Evaluation Form (PEF) scores, we selected a sample of 25 severely depressed and suicidal adolescents; 26 severely depressed, not suicidal adolescents; and 28 not suicidal, not depressed adolescent inpatients at The Sheppard and Enoch Pratt Hospital. A Rorschach Index using the Exner (1986) Comprehensive System for scoring was developed to predict group membership. Four of six of the features on this index selected 64% of suicidal subjects. This constellation included traditional affective variables (vista responses, color-shading blends, color dominated responses, and morbid content) as well as measures of cognitive distortion (inaccurately perceived human movement responses [M-] and special scores). We discuss the implications of these findings for the diagnosis and treatment of the suicidal adolescent. PMID- 1432562 TI - Personality in panic disorder with agoraphobia: a Rorschach study. AB - In this study, we tested several hypotheses derived from self psychology (Diamond, 1987) regarding personality features of patients suffering from panic disorder and agoraphobia (PDA). PDA patients are thought to suffer from a deficit in negative affect-regulating capacity, surrounded by defenses such as avoidance, repression, denial, and reaction formation against dependency needs. These defenses are thought to lead to a greatly impoverished affective life. The Rorschach Comprehensive System was used to assess the personality features of avoidance, restricted affective life, and reaction formation against dependency needs. We found evidence for the presence of a highly avoidant information processing style (86% of protocols had lambda [L] greater than .99) and a constricted affective life (low weighted sum color [WSumC] and low affective ratio [Afr]). Our results were consistent with the hypothesis of reaction formation against dependency needs (low food content [Fd]). Findings are discussed in light of studies that found a high incidence of avoidant personality disorder in PDA patients. PMID- 1432563 TI - The response of African Americans to the Rorschach: a review of the research. AB - Studies exploring the performance of African Americans on the Rorschach were reviewed. The review revealed the limited number of studies done in this area of study, as well as the fact that the research paradigm for all of this research has been limited to comparing the Rorschach performance of African Americans to that of Whites. However, no one has offered a rationale for such a research paradigm. Without a scientific reason to expect personality to be a function of race, another research design was recommended, one that explores the effect of a variety of aspects of living conditions on the development of the personality of African Americans. PMID- 1432564 TI - Toward the clarification of the construct of depersonalization and its association with affective and cognitive dysfunctions. AB - Little consensus or systematic research exists regarding the symptoms that constitute depersonalization and its association with affective and perceptual dysfunctions. A scale was constructed to measure depersonalization experiences reported in the literature and four items representing psychotic symptoms. Five factors representing different types of depersonalization emerged: Inauthenticity, Self-Negation, Self-Objectification, Derealization, and Body Detachment. Based on the factors, scales were constructed; these scales have internal consistency ranging from .78 to .84. Each of these factor scales was factorially distinguishable from psychosis and correlated between .48 and .58 with the Jackson and Messick (1972) Feelings of Unreality Scale, suggesting divergent and convergent validity. Inauthenticity, the most frequent and pervasive form of depersonalization experience, was best predicted by a cognitive style featuring intense, critical examination of self and others. In contrast, Self-Objectification was best predicted by thought disorganization and perceptual distortion and was experienced somewhat infrequently by relatively few subjects. All forms of depersonalization were associated with depression, except Inauthenticity. PMID- 1432565 TI - Some reflections on the meaning of psychodiagnosis. 1971. PMID- 1432566 TI - Hypotensive effect of a phosphorus-containing novel angiotensin converting enzyme inhibitor, (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl)phosphinyl] oxy]-1-oxohexyl]-L proline (SQ 29,852) in conscious hypertensive dogs. AB - The hypotensive efficacy of (S)-1-[6-amino-2[[hydroxy(4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]-L-proline (SQ 29,852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI) was examined in conscious two kidney, one-clip Goldblatt hypertensive dogs. The acute hypotensive effect of SQ 29 852 was compared with that of captopril or enalapril at 3 mg/kg, p.o., for each, and the potencies were ranked as follows, enalapril greater than SQ 29,852 greater than captopril. On the other hand, the hypotension caused by repetitive dosing with SQ 29,852 (3 mg/kg, p.o./d for 7 d followed by another 7-d treatment with 10 mg/kg, p.o./d) was somewhat more marked than that by enalapril at the same dosage. Blood urea nitrogen (BUN) increased in all the animals given enalapril, while that in all of the SQ 29,852-treated animals did not increase. These results indicate that SQ 29,852 is a potent, and long-lasting ACEI with a possible low incidence of side effects. PMID- 1432567 TI - Activation of the complement system by (1----3)-beta-D-glucans having different degrees of branching and different ultrastructures. AB - Activation of the alternative (APC) and classical (CPC) pathways of complement by fungal (1----3)-beta-D-glucans having different degrees of branching (DB) and different conformations were examined by using human serum and plasma. The glucans used in this study were curdlan (no branch; 0/1), grifolan (one branch in every third main chain unit; 1/3), schizophyllan (1/3), SSG (1/2), and OL-2(2/3). Triple or single helix conformer of these glucans were prepared by heating at 150 degrees C or dissolution in sodium hydroxide. Activation of APC by these glucans were dependent on incubation time, concentration, molecular weight, and DB. Interestingly, the triple helix conformer of all glucans tested activated APC stronger than a single helix one. The activity of branched glucans in plasma was weaker than those in serum. On the other hand, in the case of CPC, a single helix conformer activated CPC stronger than a triple helix one, and the activity was dependent on DB. Activation of CPC by a single helix conformer was thought to be dependent on the binding of beta-glucan to immunoglobulin in serum, because the complex was clearly detected by gel permeation chromatography only in the case of single helix one. From these results, it appears that the different conformers were recognized by the host complement systems in different ways. (1----3)-beta-D Glucan is one of the major constituents of fungal cell wall and is thought to be clearly recognized by the host immune systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432568 TI - Clinical management of boric acid ingestion: pharmacokinetic assessment of efficacy of hemodialysis for treatment of acute boric acid poisoning. AB - Seven hours after suicidal ingestion of about 21 g of boric acid, a 26-year-old female admitted to our hospital in a state of slightly impaired consciousness, with frequent vomiting, shivering, fever and skin flush. Immediately, gastric lavage, followed by administration of activated charcoal and laxative (MgSO4), was performed. In order to ensure her urination, fluid infusion therapy was conducted with the aid of diuretics (furosemide). Since the serum concentrations of boric acid was very high, hemodialysis was carried out twice during the first 39 h. She responded well to the above mentioned treatment and was discharged 12 d post-admission without any sequelae. The concentrations of boric acid in serum and urine were measured in appropriate intervals with our modified Miyamoto's method, and the pharmacokinetics of boric acid were analyzed. The concentration of boric acid in serum and urine at the beginning of treatment was 465 micrograms/ml and 3.40 mg/ml, respectively. The half-life of boric acid in serum was 13.46 h, whereas it was shortened to 3.76 h during hemodialysis. The total body clearance was 0.99 l/h, while it increased to 3.53 l/h by hemodialysis. The additional removal of boric acid by hemodialysis was estimated to be about 5 g. It was concluded that the hemodialysis was very useful in the treatment of boric acid poisoning, because it accelerated the elimination of boric acid about four times faster than with conventional treatment. PMID- 1432569 TI - Brain and cerebrospinal fluid distributions of metoprolol in rats. AB - The distribution of metoprolol tartrate (MPL) into the brain and cerebrospinal fluid (CSF) from plasma was determined at 2 different steady-state plasma concentrations (2 and 20 nmol/ml) and following intravenous bolus administration (100 nmol/kg) in rats. Under steady-state condition, no difference in the brain and CSF distributions of MPL was observed between 2 different plasma MPL concentrations, and the value of brain- or CSF-to-plasma partition coefficients were 5.7 and 1.5, respectively. Following intravenous administration, MPL distributed into CSF very rapidly and its initial uptake phase was not detected. On the other hand, MPL distribution into the brain was relatively slow with the uptake phase. Thus, the brain uptake of MPL from the plasma was pharmacokinetically analyzed using a modified 2-compartment model and deconvolution method, whereas the CSF distribution of MPL was not adequate for kinetic analysis because of the lack of uptake phase. The analysis of brain uptake of MPL by both compartment model and deconvolution gave the same results and the calculated brain Kp value of MPL was almost comparable with that of observed Kp value under steady-state plasma concentration. The distribution of MPL into CSF was considered mainly depending on the pH difference between the plasma and CSF, and the mutual transfer of MPL between CSF and the brain tissue was considered to be negligible from an in vitro study. PMID- 1432570 TI - Inducible resistance to a 16-membered macrolide, mycinamicin, in Staphylococcus aureus resistant to 14-membered macrolides and streptogramin B antibiotics. AB - Staphylococcus aureus 8325(pEP2104), a transductant derived from S. aureus PM2104 isolated clinically in Hungary (L. Janosi, and E. Ban, Acta Microbiol. Acad. Sci. Hung., 29: 187-200, 1982), exhibited an inducible resistance to the 14-membered macrolides [erythromycin (EM) and oleandomycin (OL)] and streptogramin B (MKM-B) antibiotics, but not to the 16-membered macrolides and lincosamides. This resistance was referred to as PMS-resistance phenotype (L. Janosi, Y. Nakajima, and H. Hashimoto, Microbiol. Immunol., 34: 723-735, 1990). In addition to EM, OL, and MKM-B, however, the strain was recently and first observed to have inducible resistance to mycinamicin, a 16-membered ring macrolide. Thereby, we propose that the reference stated just above as PMS-resistance has to be extended to such 16 membered macrolides as mycinamicin. An optimum concentration of erythromycin or oleandomycin for induction of PMS-resistance was 1.35 mu g/ml in the strain 8325(pEP2104). The concentration was about 30 times as great as that (0.05 mu g/ml) required for induction of well-known co-resistance to macrolide-lincosamide streptogramin B antibiotics in S. aureus ISP447. PMID- 1432571 TI - Food restriction enhances melatonin effects on the pituitary-gonadal axis in female rats. AB - The effects of melatonin (25 micrograms s.c. daily in the late afternoon for 10 days) on the ovarian morphometry and the gonadotropin secretion were investigated in food-restricted rats and rats fed ad libitum. In food-restricted rats melatonin produced the significant decrease of the surface area of the ovary and of zona granulosa. Moreover, melatonin treatment of food-restricted rats resulted in significant diminishment of the relative areas of Graafian follicles and zona granulosa estimated in relation to the ovary cross-sectional surface area. On the other hand, melatonin did not produce significant alterations of the morphometric indices of the ovary in rats fed ad libitum. Melatonin administration was found to inhibit the effects of gonadoliberin on gonadotropin release in food restricted but not in normally-fed rats. These findings suggest that food restriction sensitizes the pituitary-ovarian axis to antigonadotropic melatonin action. PMID- 1432572 TI - Melatonin inhibits mammary gland development in female mice. AB - The objective of this study was to determine whether melatonin (aMT) influences the postnatal development of the mammary gland parenchyma in female mice from the time of weaning to adulthood. Twenty-one-day-old female BALBc mice were treated with daily subcutaneous injections of aMT (200 micrograms) or diluent, 3 hr before the onset of darkness (photoperiod LD 12:12). At 3, 5, 7, 9, 11, and 13 weeks of age, batches of 20 animals (ten controls and ten aMT-treated) were sacrificed and the second pair of mammary glands were dissected to evaluate their degree of development. Melatonin decreased body weight gain from 2 weeks before until 2 weeks after the onset of puberty. Treatment with aMT also resulted in a lower DNA content and smaller area of the mammary gland from the time of puberty until the end of the study. In aMT-treated mice the phase of highly positive allometric growth began 2 weeks later, but ended at the same time as in controls (11th week of life). Finally, aMT decreased the development of terminal, lateral, and alveolar buds while it increased the number of terminal ducts per gland. We conclude that pharmacological doses of aMT (1) reduce body weight gain at the peripuberal age; (2) partially inhibit postnatal mammary gland development by reducing the number of epithelial structures representing sites of growth and increasing that of structures representing the final state of ductal growth in virgin animals; (3) delay the onset of the shorten the phase of rapid mammary growth occurring in early postpuberal age. PMID- 1432573 TI - Regulation of the androgen receptors in the harderian gland of the male Syrian hamster: influence of photoperiod, castration, and chronic melatonin treatment. AB - Male Syrian hamsters that were exposed for 8 weeks to short photoperiod (LD 10:14) or treated with melatonin in the late afternoon under long photoperiod conditions (LD 14:10) had a significantly higher content of androgen receptors in the Lipidex-purified soluble fractions isolated from the Harderian glands as compared to the long photoperiod (LD 14:10) exposed controls. Simultaneous computer-assisted analyses of all series of saturation and competition experiments revealed that the numerical value of the apparent Kd, as determined by using the synthetic androgen R-1881 (methyltrienolone), was not different between the experimental groups, and ranged from 0.050 to 0.067 nM. Of the principal natural androgens, testosterone (T) was most potent in inhibiting methyltrienolone binding to the receptor (Ki values from 0.33 to 0.55 nM), and 5 alpha-dihydrotestosterone (DHT) and delta 4-androstenedione (AD) were less effective (Ki values between 1 and 1.9 nM). In the hypothalami and pituitaries of the same animals, used in parallel control assays, DHT was twice as potent as T. Short-term castration (24 hr post-orchidectomy) did not result in significant changes in the receptor binding characteristics. Following 8 weeks exposure to a long photoperiod (LD 14:10) the Bmax values demonstrated a four-fold increase in castrated animals (179 fmoles/mg protein vs. 47 fmoles/mg protein) over intact controls. The relative binding affinity of the major androgens under these conditions remained unchanged, with the exception of AD, where a five-fold increase in the numerical Ki values (decrease in the binding affinity) was recorded (Ki = 9.6 nM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432575 TI - Interruption of nocturnal pineal melatonin synthesis in spontaneous recrudescent Djungarian hamsters (Phodopus sungorus). AB - The duration of nighttime synthesis of the pineal hormone melatonin is believed to determine the breeding season in many mammalian species. Hamsters exposed to short days undergo gonadal involution followed by a return to normal function, suggesting a developed insensitivity to regressive photoperiods. This recrudescence may be due to either exhaustion of the pineal or to target desensitization. Both theories have been tested previously but failed to explain this phenomenon. We performed an experiment in the Djungarian hamster (Phodopus sungorus), a well-characterized photosensitive species with a type C melatonin pattern (prolonged peak during majority of dark phase), in an attempt to resolve this issue. Among age-matched male hamsters exposed to short days for either 16 weeks (involuted) or 38 weeks (spontaneous recrudescent), marked phase differences in diurnal pineal melatonin rhythms were observed. Furthermore, in recrudescent hamsters the melatonin pattern was divided into two parts, possibly no longer recognizable as a typical short-day rhythm. PMID- 1432574 TI - Seasonal variations in pineal 5-methoxytryptophol (5-ML) concentrations and in the daily pattern of pineal 5-ML and melatonin in the desert rodent Jaculus orientalis: effect of prolonged illumination during the night. AB - Seasonal variations in daytime pineal 5-methoxytryptophol (5-ML) and in the daily pattern of both pineal 5-ML and melatonin concentrations were measured by radioimmunoassay in male and female jerboas, Jaculus orientalis. Pineal 5-ML content was found to be low in winter and spring and showed a short but marked increase in summer. A clear daily rhythm was present in pineal 5-ML in September, with high concentrations during daytime and low concentrations during nighttime. In May there was a considerable drop in the daytime values and a marked decrease in the amplitude of the rhythm, while in December the daily rhythm completely disappeared. On the contrary, a clear daily rhythm was observed for pineal melatonin in September, December, and May with high values during nighttime and low values during daytime; no differences in the amplitude of the rhythm could be observed. Illumination during early night prevented both the nocturnal decrease of 5-ML and the increase of melatonin in September; in May illumination had no clear effect on 5-ML, while it prevented the normal increase of melatonin. These results suggest a possible desynchronization between the regulation of 5-ML and melatonin synthesis and release, and stress the complexity of the mechanisms involved in the environmental synchronization of seasonal functions. PMID- 1432576 TI - A phase-dependent delay of the chick pineal rhythm in rate of thymidine incorporation by brief exposure to ouabain. AB - Cultured chick pineal glands show a persistent rhythm in the rate of cumulative incorporation of thymidine into DNA [Wainwright and Wainwright, 1989]. In this study we have examined the effects of a pulse-exposure to ouabain in the dark on the first day of culture upon thymidine incorporation during the second and third days of culture in the dark with ouabain-free medium. The phase of the rhythm in rate of thymidine incorporation was delayed by a 4-hr exposure to 100 microM ouabain commencing in the final hour of the photoperiod, but not by a 2-hr exposure or by 10 microM ouabain. This effect was phase-dependent and not seen when exposure to ouabain began earlier in the photoperiod. The phase delay caused by ouabain was not due to a persistent direct inhibition of the process of thymidine incorporation. The phase-shift due to exposure to ouabain was superimposed on a phase delay caused by renewal of culture medium 4 hr after explanting the glands into culture. PMID- 1432577 TI - A new biodegradable elastin-fibrin material; its use in urological, digestive and cardiovascular surgery. AB - A new original artificial connective matrix mainly made of elastin and fibrin like product is used to reinforce damaged tissues and to close and restore a loss of substance in several domains of surgery: all sites in the digestive system and urinary tract; besides, it can substitute for the pericardium in iterative heart operations. In all cases, the original tissue is restored ad integrum while the biodegradable material disappears completely, without any complications. PMID- 1432578 TI - Polymeric membranes for silicon based (bio)sensors. AB - During the last decade, chemical and biochemical sensor research has benefited from the availability of new technologies and materials. New embodiments of classical devices have resulted from the use of e.g., solid state technology for the realization of the transducers. In this paper we describe several examples of membrane deposition techniques used in connection with planar, silicon based electrochemical transducers. Casting and electrochemical deposition of glucose oxidase containing membranes are described for the fabrication of glucose enzyme electrodes. Photolithographic patterning of polyacrylamide hydrogel and of siloxane based gas permeable membrane is used for the realization of an amperometric oxygen sensor and an ISFET-based pCO2 device. The last example is that of a free-chlorine sensor for which the photolithographic patterning of the polyHEMA hydrogel layer is described. PMID- 1432579 TI - Effect of pretreatment with epoxy compounds on the mechanical properties of bovine pericardial bioprosthetic materials. AB - Early failures of bovine pericardial heart valves are due to leaflet perforation, tearing and calcification. Since glutaraldehyde fixation has been shown to produce marked changes in leaflet mechanics and has been linked to development of calcification, bovine pericardium fixed with the four hydrophilic epoxy formulations and their mechanical properties are studied in this paper. We measured the thicknesses, shrinkage temperatures, stress relaxations and stress strain curves of bovine pericardiums after different treatments with (1) non treatment (fresh), (2) glutaraldehyde (GA), (3) epoxy compounds followed by the posttreatment with GA (EP 1#, EP 2#), and (4) epoxy compounds (EP 3# and EP 4#). Results of this study showed that the hydrophilic epoxy compounds are good crosslinking agents. There are no significant differences of shrinkage temperature and ultimate tensile stress among all tissue samples pretreated with GA, EP 1# and EP 2#. However, the stress relaxations of tissue-samples pretreated with epoxy compounds followed by the posttreatment with GA (EP 1# and EP 2#) are significantly slower than that pretreated with GA, and the strains at fracture of EP 1# and EP 2# are also significantly larger than that of GA or epoxy compounds. These facts show that the bovine pericardium pretreated with the epoxy compound followed by the posttreatment with GA (EP 1# and EP 2#) possesses greater tenacity and potential durability in dynamic stress. PMID- 1432580 TI - Bioactive polymers 55. Synthesis and characterization of a macromolecular drug based on 5-acetylamino-2-sulfamoyl-1,3,4-thiodiazole. AB - The paper studies the coupling reaction by covalent bonding of acetylamino-2 sulfamoyl-1,3,4-thiodiazole (AcAA) on the poly(acrylic acid-costyrene) copolymer (PAcA-S) in homogeneous system, in the presence of dicyclohexylcarbodiimide (DCC) as activator. The influence of some factors on coupling efficiency (the drug/support ratio, time, volume of solvent), as well as the mathematical model correlating the amount of coupled drug with these parameters is established. Maximum amounts of drug (28%) are chemically bound when employing maximum values of the parameters mentioned (i.e., AcAA/PAcA-S ratio = 2 mole/mole; time = 50 h; THF volume = 60 ml). Physicochemical and spectral analyses evidence the existence of some chemical bonds of the -CO-NH-SO2-type between the macromolecular support and the drug. In vivo tests have demonstrated the gradual hydrolysis of the chemical bonds as well as the release of the drug, due to the diuretic effect produced. PMID- 1432581 TI - Nursing in child psychiatric milieus: Part I: What nurses do. AB - Because of the reduced length of inpatient hospitalization and the increasing emphasis on biopsychiatric treatments, milieu psychiatry is in decline. However, certain aspects of the therapeutic milieu are essential to the operation of child inpatient units. Children with acute psychiatric illness need a safe, structured, and supportive environment. Nurses are the professional group responsible for instituting and maintaining this type of environment, yet their specific functions are vaguely stated and often intuitively derived. A useful way to delineate and describe what nurses do is to organize nursing behaviors into five therapeutic processes: (a) safety, (b) structure, (c) support, (d) involvement, and (e) validation. By delineating essential milieu dimensions in this way, the form and purpose of nursing interventions are clarified. PMID- 1432582 TI - Nursing in child psychiatric milieus: Part II: Mapping conceptual footholds. AB - In the first part of this paper, child inpatient nursing practice was organized into five therapeutic processes (safety, structure, support, involvement and validation). Using this organization of nursing care, three specific practice question are now addressed. One, how will nursing blend their traditional psychosocial orientation with biological psychiatry? Two, how might nurses best respond to the pressure to reduce the length of hospitalization yet still effectively intervene with troubled children? Three, does the traditional milieu therapy model have clinical utility for child inpatient nurses in the 1990's. It is suggested that nursing practice is best supported by multiple midrange theories which clarify children's behavior and give theoretical support to specific nursing interventions. PMID- 1432583 TI - The effect of a bereavement group experience on bereaved children's and adolescents' affective and somatic distress. AB - Losing loved ones through death is a common experience for children. Children living in urban centers may be at greater risk for death of family members as a result of increased daily stress and poverty. Children who experience permanent loss of family members without support to grieve are at greater risk for mental health problems. Manifestations of grief that frequently occur in children are psychosomatic complaints and affective distress. This study investigates the prevalence of loss by death among two groups of inner city youths, and the impact of a bereavement group experience on subjects' affective distress and somatic complaints. A significant difference was found between pretest and post-test scores on somatic complaints for the elementary school aged group. PMID- 1432584 TI - Multiple family therapy for adolescents: a case illustration. AB - Psychiatric hospitalization of adolescents is on the rise, with the concurrent trend toward shorter stays and increased need for expedient, effective treatment modalities. Involving families or troubled adolescents in all phases of treatment is believed to be essential and aids both in successful reintegration of the patient into the community and prevention of relapse. Psychiatric nurses can practice innovative therapies to meet the needs of hospitalized adolescents and their families. Clinical observations have shown multiple family therapy for adolescents to be a valuable component of care. PMID- 1432585 TI - Impressions of the National Hearing on Severe Mental Illness and Homelessness. PMID- 1432586 TI - Preparing to parent the adolescent: a theoretical overview. AB - Early adolescence (ages 11-14 years) occurs at the time most parents are in middle adulthood. The tasks of both early adolescent and middle adulthood stages are numerous and complex. As a societal unit, the family is challenged to meet one another's needs for cohesion, adaptability, and satisfaction. Family communication and the family's ability to resolve conflicts are proposed as facilitating factors to meet these challenges. PMID- 1432587 TI - Nurses develop a plan for research on child and adolescent mental disorders. PMID- 1432588 TI - Sibling incest: a descriptive study of family dynamics. AB - This study investigates the characteristics of families in which a member was identified as a victim of sibling incest. Four agencies in a southeastern city provided a convenience sample of 14 family case records from November 1986 through April 1988 for review. Sixteen children were identified as victims of sibling incest, including three boys and 13 girls between the ages of 2 and 10 years (mean = 6.75 years). Perpetrators included 1 girl and 14 boys between the ages of 13 and 17 years (mean = 15.06 years). The incestuous relationship had a major impact on families, especially the children. Many offenders and victims, in addition to experiencing emotional, school, and legal problems, were removed from their homes. PMID- 1432589 TI - [Translocation mechanism of presecretory protein across the cytoplasmic membrane of Escherichia coli]. AB - Translocation of presecretory proteins across the cytoplasmic membrane of Escherichia coli requires several Sec proteins and two kinds of energies, adenosine triphosphate (ATP) and a proton motive force. In vitro assay system established for the analysis of protein translocation revealed that ATP and the proton motive force play different roles in protein translocation. SecA, a peripheral membrane protein, was shown to be essential for in vitro protein translocation. SecE and SecY, both of which are integral membrane proteins, were purified from E. coli cells overproducing these proteins, and reconstituted into proteoliposomes. The reconstituted proteoliposomes exhibited protein translocation activity in the presence of ATP and SecA, indicating that SecE and SecY as well as SecA are indispensable components of protein translocation machinery. In this paper, the molecular mechanism of protein translocation across the membrane of E. coli is discussed based on the recent data obtained by both in vitro and reconstitution systems. PMID- 1432590 TI - [Structural alterations of the N-linked sugar chains of glycoproteins produced by tumor cells and their clinical application]. AB - Enrichment of complex type N-linked sugar chains containing the Gal beta 1--- 4GlcNAc beta 1----6(Gal beta 1----4GlcNAc beta 1----2)Man group was found to be the structural background of Warren-Glick phenomenon. This alteration is induced by enhanced expression of N-acetylglucosaminyltransferase V in malignant cells. The phenomenon is positively correlated with the tumorigenicity and the potency of blood-borne metastasis of tumor cells. Further investigation of the surface sugar chains of lectin mutants of mouse B16 melanoma revealed that the occurrence of sialylated tetraantennary sugar chains is essential for the metastasis of tumor cells. PMID- 1432591 TI - [Hypoglycemic activity of polysaccharide fraction from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao and the effect on carbohydrate metabolism in normal mouse liver]. AB - The ethanol precipitate fraction (RG-WP) obtained from the hot water extract from rhizome of Rehmannia glutinosa Libosch. f. hueichingensis Hsiao is mainly composed of pectin-like polysaccharide, and exhibited hypoglycemic activity in normal and streptozotocin-induced mice by intraperitoneal administration of the fraction. The results obtained after chemical modification and proteinase treatments of RG-WP suggest that the activity exists in the polysaccharide moiety. Furthermore, the effect of RG-WP on the activities of enzymes responsible for the glucose metabolism in the liver of normal mouse was studied to elucidate the mechanism of the hypoglycemic activity. Administration of RG-WP to normal mice significantly increased the activities of hepatic glucokinase and glucose-6 phosphatase dehydrogenase, but decreased those of hepatic glucose-6-phosphatase and phosphofructokinase. RG-WP stimulated the secretion of insulin and reduced the glycogen content in the liver of normal mouse. PMID- 1432592 TI - [Crystal morphological and habit investigations of crystalline drugs. I. Phenytoin]. AB - Crystal morphology and crystal habit of phenytoin crystals were studied by the immersion method using a polarizing microscope. Several kinds of phenytoin materials, which had been confirmed to be lying on the same orientation by measuring key refractive indices, were photographed under crossed polars. The relationship between the patterns of retardation colors and the shapes of the phenytoin crystals were analyzed quantitatively using the chart indicating the relation of thickness to retardation colors, and concurrently several necessary facial angles were measured. On the basis of these results as well as edge angles measured under a microscope a stereographic projection was drawn finally, and an orthorhombic symmetry, an axial ratio and some facial angles were determined. Several kinds of crystal habits observed from the photographs were drawn by the classic crystallographic habit drawing method using the stereographic projection. PMID- 1432593 TI - [Preparation of phenyl treated packing materials for high-performance liquid chromatography: evaluation by retention behaviour of carbamazepine and diphenylhydantoin]. AB - The retention behavior and selectivity of 30 kinds of phenyl-modified porous glasses and silicas, prepared from solutions of phenyldimethylchlorosilane, diphenylmethylchlorosilane or triphenylchlorosilane in xylene, were studied by high-performance liquid chromatography using carbamazepine and diphenylhydantoin as model compounds. From the elemental data for carbon, the maximum number of bonded phenyl groups per gram (mean pore diameter, 15 nm, specific surface area, 217 m2/g, pore volume, 0.85 ml/g) on the diphenyl-bonded glass surface was calculated to be 0.159 x 10(21). Using various acetonitrile-0.01 M potassium dihydrogen phosphate mixtures as eluents, carbamazepine and diphenylnydantoin were separated on all the gels studied, but the degrees of resolution of the two compounds were different. With an increase in specific surface area on the glasses or silicas, the k' values of the solute increased. PMID- 1432594 TI - [Determination of the main metabolite (desethyl KBT-3022) of a new antiplatelet agent, KBT-3022 in plasma by gas chromatography]. AB - A highly sensitive, accurate and reproducible gas chromatographic method for the determination of a main metabolite, 2-[4,5-bis(4-methoxy-phenyl)thiazol-2-yl] pyrrol-ylacetic acid (desethyl KBT-3022) of a new antiplatelet agent, ethyl 2 [4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate (KBT-3022), in the human or dog plasma has been developed. Desethyl KBT-3022 in the plasma was extracted with a mixture of n-hexane and dichloromethane (1:1), and was derivatized using pentafluorobenzyl bromide. The obtained pentafluorobenzyl derivative of desethyl KBT-3022 in the plasma was separated by high-performance liquid chromatography. After the separation, the pentafluorobenzyl derivative of desethyl KBT-3022 was detected by gas chromatography. Gas chromatography was performed with a Ultra 1 column (12 m x 0.22 mm i.d., film thickness 0.33 microns), using an electron capture detector. 2-[2-(4,5-Bis(4-methoxyphenyl)thiazol-2-yl)pyrrol-l yl]propionic acid was used as an internal standard. The detection limit of desethyl KBT-3022 in the plasma was 0.2 ng/ml. The coefficients of variation were below 5.3%. This method was applied to the determination of the plasma concentration of desethyl KBT-3022 after oral administration of KBT-3022 to dogs. PMID- 1432595 TI - [Elucidation of biosynthetic process and regulation mechanism of bioactive peptides and their receptors]. AB - To elucidate the mechanism of proinsulin induction by glucose, we determined the amount of proinsulin messenger ribonucleic acid (mRNA), the subcellular distribution of proinsulin mRNA and the transcriptional activity of proinsulin gene in isolated pancreatic islets of rat. From these results, we concluded that the stimulation of proinsulin synthesis was mainly regulated at the translational level. To elucidate the primary structure of vasoactive intestinal peptide (VIP) precursor, we determined the nucleotide sequence of VIP complementary deoxyribonucleic acid (cDNA). The entire amino acid sequence of the VIP precursor indicates that the precursor protein contains not only VIP but also PHI-like peptide. We also found that the induction of pro-VIP synthesis was achieved by enhancing the transcription rate of VIP gene. We also isolated fibroblast growth factor (FGF) receptor cDNA. The nucleotide sequence of FGF receptor cDNA indicates that the receptor is a transmembrane protein that contains extracellular immunoglobulin-like domains and an intracellular tyrosine kinase domain. We also found that the receptor had two isoforms of the extracellular domains and that the expression of the isoforms was regulated tissue specifically. PMID- 1432596 TI - [Prostaglandins: synthetic and pharmacological studies and development]. AB - The therapeutic use of prostaglandins (PGs) which contain various biological activities and are unstable was successfully achieved. PGs were produced in a large scale according to the Corey method and could be stabilized by the formation of a clathrate compound with cyclodextrin, which enabled the production of marketable form of highly pure PGs. Diligence in the development of native PGs and their structural analogs for human therapy resulted in the following six drugs now being on the market in Japan: PGF2 alpha as the first drug of PGs in the world which induces labor; PGE2 as an orally active labor inducing drug; PGE1 for the treatment of peripheral vascular diseases; gemeprost for therapeutic abortion in the middle-term; ornoprostil, as an oral anti-ulcer agent; limaprost for the treatment of peripheral vascular diseases as an oral agent. PMID- 1432597 TI - [Syntheses and central depressant activity in mice of uracil derivatives. Studies on development of new sedative-hypnotics. II]. AB - Fifteen kinds of uracil derivatives, which were substituted with functional groups such as benzyl (Bn), methoxymethyl (MOM), n-propyl (Pr) or allyl (A) group at the N1 and/or N3 position of uracil, were synthesized. Sedative-hypnotic activity, pentobarbital (PB)-induced sleep prolongation and acute toxicity as indices of their pharmacological activities were evaluated using mice. Spontaneous activities of mice treated with N1-benzyluracil (N1-BnU, 7), N3 benzyluracil (N3-BnU, 8), N1,N3-dibenzyluracil (DBnU, 9), N1-benzyl-N3 allyluracil (BnAU, 14) and N1-allyl-N3-benzyluracil (ABnU, 15) were measured. Ten kinds of uracil derivatives showed hypnotic activity. ED50's values of ABnU (15) and N1-propyl-N3-benzyluracil (PrBnU, 13) were 155 and 172 mg/kg, i.p., respectively. Those effects were more potent than that of barbital (179 mg/kg, i.p.) Ten kinds of uracil derivatives tested significantly prolonged the PB induced sleeping time. N3-BnU (8) increased the spontaneous activity of mice at a dose of 80 mg/kg, i.p., while ABnU (15) depressed the spontaneous activity at a dose of 160 mg/kg, i.p. The other compounds did not show any significant effect on the spontaneous activity of mice. LD50's values of ABnU (15), PrBnU (13) and N1-methoxy-methyl-N3-benzyluracil (MOMBnU, 11) were 199, 229 and 363 mg/kg, i.p., respectively. LD50's values of the other derivatives were more than 480 mg/kg, i.p. These results indicate that the benzyl group at the N3 position of uracil is important for exhibiting sedative-hypnotic activity of uracil derivatives, and that ABnU (15) has the most potent central depressant activity among the uracil derivatives tested. PMID- 1432598 TI - [Studies on zwitter-ionization of drugs. I. Synthesis and pharmacological activities of N-alkylcarboxylic acid derivatives of 4-(2-chlorodibenz [b,f][1,4]oxazepin-11-yl)piperazine, 4-(2-chlorodibenzo[b, f]-[1,4]thiazepin-11 yl)piperazine, and 4-(11H-dibenz-[b,e]azepin-6-yl)piperazine]. AB - The piperazine N-alkylcarboxylic acids of 2-chlorodibenz[b,f][1,4] oxazepine (3a), 2-chlorodibenzo[b,f] [1,4] thiazepine (3b), and dipenz[b,e] azepine (3c) from the corresponding piperazines (1a-c, R1 = H) were synthesized via the piperazine N-alkylcarboxylates (2a-c). The pharmacological activities of the piperazine N-alkylcarboxylic acids (3a-c) were evaluated. Compared with the parent compounds (1a-c), 3a-c (n = 1-5) showed weak inhibitory activities on the uptake of noradrenaline and 5-hydroxytryptamine (5-HT) into hypothalamus vesicles and moderate antagonistic actions to 5-HT2 and H1 in several tissues. PMID- 1432600 TI - [Elucidation on abnormal behavior of glycyrrhizin salts in high performance liquid chromatography determination for quasi-drug products]. AB - Glycyrrhizinates such as monoammonium and dipotassium glycyrrhizinates which are extracted from licorice, converted to easily water-soluble salts and refined have been formulated in many quasi-drug products as an anti-inflammatory agent. A quantitative analysis of glycyrrhizinates in quasi-drug products has usually and successfully been carried out by high performance liquid chromatography (HPLC). However, a slightly higher value than the actual content has sometimes been observed in daily analysis. As the result of our various studies to investigate these phenomena, we finally found that a minor constituent in commercial glycyrrhizinates, which was identified as monomethyl glycyrrhizinate, was hydrolyzed after they were formulated in quasi-drug products and converted to glycyrrhizin which in turn was determined by HPLC as a higher value. PMID- 1432599 TI - [Pharmacological study on kefir--a fermented milk product in Caucasus. I. On antitumor activity (1)]. AB - The antitumor activity of kefir (YK-1), a fermented milk product in Caucasus, was investigated. YK-1 at oral doses of 100 or 500 mg/kg inhibited the proliferation of solid tumor of Ehrlich ascites carcinoma transplanted subcutaneously in mice. YK-1 did not show an inhibitory effect on the ear swelling induced contact dermatitis caused by picryl chloride (PC-CD). However, YK-1 inhibited the immunosuppression in Ehrlich carcinoma-bearing mice and with the frozen and dried ascites of the tumor-bearing mice containing immunosuppressive substances (EC sup) in PC-CD-induced mice. And also, YK-1 activated the immunosuppressive activity of spleen cells of mouse treated with EC-sup. These results suggest that YK-1 may have antitumor activity against Ehrlich carcinoma and activate the immunosuppression with it. PMID- 1432601 TI - [Disposition analysis by fast inverse Laplace transform (FILT)]. AB - A curve fitting program, MULTI (FILT), in which an algorithm of fast inverse Laplace transform is incorporated, was introduced into the area of drug disposition. The reliance of MULTI (FILT) was verified by the Monte Carlo simulation based on compartment models. MULTI (FILT) was applied to the analysis of the local dispositions of drugs through the liver, including the construction of new dispersion model, the effect of albumin in perfusate, and the effect of perfusion rate. The elimination in the lung and the enterohepatic circulation were also evaluated using MULTI (FILT) in a simple manner. PMID- 1432602 TI - [Stability studies on 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2 yl)amino]benzoate dimethanesulfonate (FUT-187) in aqueous solution]. AB - FUT-187 (I), 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethanesulfonate, is a new synthesized proteinase inhibitor. Decomposition kinetics and photoreactivity of I in aqueous solution were studied. In aqueous solution, I was hydrolyzed to its moieties, [4-(4,5-dihydro-1H imidazol-2-yl)amino]benzoic acid (IABA) and 6-amidino-2-naphthol (AN). The hydrolysis followed a pseudo-first order reaction. I was stable under acidic condition between pH 2 and pH 3 and decomposed by irradiation from xenon light to form IABA, AN and compound II. The structure of II was studied by nuclear magnetic resonance, infrared, mass and ultraviolet spectra and identification tests. It was shown that II was 6-amidino-2-hydroxy-1-naphthyl[4-(4,5-dihydro-1H imidazol-2-yl)amino]- phenyl ketone, benzophenone derivative, produced by photorearrangement reaction of I. PMID- 1432603 TI - [Application of the limulus amebocyte lysate test to measurement of endotoxin in therapeutic human plasma protein fraction. Comparison with the rabbit pyrogen test]. AB - We applied the limulus amebocyte lysate (LAL) test to the detection of bacterial endotoxins in therapeutic human plasma protein fraction (PPF) and compared the LAL-test with the rabbit pyrogen test. Two endotoxin-specific LAL-reagents were used for the colorimetric method and turbidimetric kinetic method. The amounts of added endotoxin to the PPF were correctly estimated by either method. The results of four independent assays for the 53 samples of PPF corresponded well with each other (correlation coefficient: 0.851-0.959, regression coefficient: 0.898 1.151). The amounts of endotoxin in the PPF estimated by the LAL-test significantly correlated with the rise of body temperature in rabbits (correlation coefficient: 0.547-0.642, and 0.911-0.934 for the endotoxin added samples). These results suggest that the LAL-test could be used as an alternative method for the rabbit pyrogen test to PPF. PMID- 1432605 TI - [Structures of isomers of ursodeoxycholic acid: 3 beta,7 alpha- and 3 beta,7 beta dihydroxy-5 beta-cholan-24-oic acids]. AB - Isomers of ursodeoxycholic acid, 3 beta,7 alpha- and 3 beta,7 beta-dihydroxy-5 beta-cholan-24-oic acids (3 beta 7 alpha U and 3 beta 7 beta U) crystallize in the orthorhombic space group P2(1)2(1)2(1) containing one molecule and in the monoclinic group P2(1) containing two independent molecules in an asymmetric unit. The cell dimensions are a = 28.032(17), b = 9.973(5), c = 8.049(6) A for 3 beta 7 alpha U, and a = 11.771(8), b = 27.999(12), c = 6.637(2) A, beta = 90.78(6) degrees for 3 beta 7 beta U, respectively. Both structures were solved by the direct method and refined to the residual values of 0.065 (3 beta 7 alpha U) and 0.059 (3 beta 7 beta U). The conformations of the D rings of each molecule are different from each other: 3 beta 7 alpha U intermediate, 3 beta 7 beta U (A and B) half-chair form. In the crystal, 3 beta 7 alpha U molecules are connected by a hydrogen bond extended nearly parallel to the bc plane and 3 beta 7 beta U molecules are connected by the helical hydrogen bond system or by the zigzag one parallel to the ac plane. PMID- 1432604 TI - [Studies on early stage changes of peroxide lipid in isoproterenol-induced myocardial injury]. AB - The amount of peroxide lipid in vivo in the early stage of the experimental model of myocardial infarction in a rat induced by the administration of isoproterenol (Isp) was measured as the value of malonic dialdehyde (MDA). The model of myocardial infarction was made by giving 75 mg/kg of Isp to the rat weighing 270 +/- 10 g. After the administration of Isp, the amounts of lipid in the serum and in the myocardial tissue were measured, and a blood chemistry test (glutamic oxaloacetic dehydrogenase, glutamic pyruvic transaminase, lactate dehydrogenase, free fatty acid, creatine kinase) was simultaneously carried out on the serum. The value of the amount of peroxide lipid in the serum began to elevate 3 h after the administration of Isp and reached a maximum value at 6 h. The value of the amount of peroxide lipid in the tissue began to elevate 30 min after the administration and reached a maximum at 3 h. Each blood chemistry disclosed the elevation 30 min after the administration. As mentioned above, the production of peroxide lipid in vivo on the myocardial disorder in the early stage after the administration of Isp and the biochemical changes showed a significant correlation. From these results it is suggested that the myocardial disorder induced by the administration of Isp has already developed at 30 min after the administration. PMID- 1432606 TI - [Antimutagenic activities of hexane extracts of the fruit extract and the kernels of Prunus mume Sieb. et Zucc]. AB - Antimutagenic activities of hexane extracts obtained from the fruit extract (UE) and the Kernels (KE) of P. mume were examined. These extracts showed inhibitory activities to known mutagens, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, benzo[alpha]pyrene and aflatoxin B1 in the Ames assay using Salmonella typhimurium TA100 and TA98 strains. The UE and KE fractions were then separated by silicic acid column chromatography with a stepwise elution method using ether hexane. The location of the active substances in the fractions was also determined by thin-layer chromatography. Consequently, it was found that the effective substances for the desmutagenicity were fatty acids, and identified by gas liquid chromatography, mainly as oleic acid, linoleic acid and linolenic acid in UE, and mainly as oleic acid and linoleic acid in KE, respectively. PMID- 1432607 TI - [Preparation of water-soluble hydronaphthoquinone derivatives and its application to the determination of hydrogen peroxide in clinical chemistry]. AB - Several 1-alkoxy-2,3-dichloro-4-hydroxynaphthalene derivatives were prepared. These compounds were oxidized by hydrogen peroxide in the presence of a peroxidase to give 2,3-dichloro-1,4-naphthoquinone, which then reacted with various alkyl benzoylacetates to develop blue coloration with absorption maximum at greater than 600 nm. The color development reaction can be applied to the determination of appropriate serum constituents such as cholesterol. PMID- 1432608 TI - Radical-induced oxidation of oxahydrindene (hexahydrobenzofuran) portion of 22,23 dihydroavermectin B1a: identification of autooxidation products. AB - Three products resulting from free-radical-induced oxidation of the oxahydrindene portion of 22,23-dihydroavermectin B1a (H2B1a) are 5-oxo-H2B1a, 8a-oxo-H2B1a, and 5,8a-bisoxo-H2B1a. The last of these compounds has not been reported previously. PMID- 1432609 TI - In vitro and in vivo anticalcification effects of novel bishydroxyiminophosphonates. AB - Some geminal bisphosphonates are used clinically for a number of important bone- and/or calcium-related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bishydroxyiminophosphonates (e.g., adipoyl- and suberoylbisphosphonate dioximes). These compounds significantly inhibited hydroxyapatite formation and dissolution in vitro and the calcification of bioprosthetic tissue implanted subdermally in rats. The compounds reported in this paper are less active than the structurally related bisacylphosphonates. The results of this work indicate that the introduction of oxime groups adjacent to the phosphonic function in long-chain bisphosphonates confers calcium interaction capabilities and that complete ionizability of a bisphosphonate may enhance its biological activity. PMID- 1432610 TI - Steady-state pharmacokinetics of haloperidol and reduced haloperidol in schizophrenic patients: analysis of factors determining their concentrations in hair. AB - Profiles of the steady-state concentrations of haloperidol (HL) and its major metabolite, reduced haloperidol (RHL), in plasma versus time were determined in 10 Japanese patients whose schizophrenic symptoms were clinically controlled by fixed, oral maintenance doses (4-30 mg/day, three times a day) for greater than 4 months. These data were used to determine the pharmacokinetic factor(s) that correlate best with HL and RHL concentrations in hair. The concentrations of HL and RHL in plasma or hair were simultaneously measured by high-performance liquid chromatography with an electrochemical detector. The observed values of minimal and maximal concentrations in plasma (Cmin and Cmax, respectively) varied widely among patients: 3.0-22.9 and 6.2-32.7 ng/mL for HL and 2.8-21.4 and 5.7-33.3 ng/ml for RHL, respectively. The ratio of the area under the plasma concentration time curve (AUC) of RHL for 1 day to that of HL also ranged widely from 0.39 to 1.99 (1.04 +/- 0.48, mean +/- standard deviation). When the concentration of HL or RHL in hair was compared with the daily dose of HL and respective AUC, Cmax, or trough concentration in the plasma in the morning, the parameter that best correlated with the concentration of HL in hair was AUC. The concentration of RHL in hair correlated with all three parameters, but the correlation with AUC was better than that with Cmax. Therefore, the concentrations of these substances in hair were considered to be representative of their mean amounts in the body. PMID- 1432611 TI - Effect of impurities on estradiol crystallization in a sustained-release implant. AB - During the development of a silicone rubber implant for the delivery of estradiol 17-beta some batches of implants made from a certain lot of commercial estradiol inexplicably developed surface crystals of estradiol after several days of storage. An impurity profile was obtained for 28 lots of estradiol by a newly developed HPLC method. One or more impurities may have had a role in the spontaneous crystal growth on the surface of the implants, because the one lot of estradiol that initially had surface crystals on aging produced acceptable implants after multiple recrystallizations. Attempts to isolate suspected impurities for characterization were unsuccessful. During the manufacture of the implants, temperatures sufficient to melt the estradiol (mp, 173-179 degrees C) were used. It was expected that, upon implant cooling, melted impure estradiol would form a thermodynamically more active (i.e., noncrystalline) physical form. This metastable form could have migrated to the implant surface, where ambient conditions favored crystallization. Because melted estradiol of a higher purity tended to crystallize more readily, it was less likely to form a glass upon cooling. The phenomenon of surface crystallization was limited to one lot of estradiol with the highest level of impurities. Data from differential scanning calorimetry studies supported this conclusion. PMID- 1432612 TI - Cholinergic agents: effect of methyl substitution in a series of arecoline derivatives on binding to muscarinic acetylcholine receptors. AB - Arecoline, arecaidine, and a series of derivatives, differing by the presence or absence of methyl groups at positions on the periphery of the molecule, were prepared, and their binding to muscarinic acetylcholine receptors was tested. On the basis of this study, muscarinic agonism for arecoline series is governed by strict structure-activity relationships, as previously observed for other agonist series. Only minor changes in nitrogen substitution were tolerated in the present series of arecoline derivatives. PMID- 1432614 TI - Pharmacokinetics and the effect of probenecid on the renal excretion mechanism of diprophylline. AB - The mechanism of renal excretion of diprophylline (DPP) and the effect of probenecid on the active transport of DPP in renal tubules were investigated in rats. The concentration of DPP in plasma increased in proportion to the doses of 10, 30, and 60 mg/kg. The pharmacokinetic parameters and the urinary excretion of DPP did not change significantly with the dose. These findings indicate that DPP possesses dose-independent pharmacokinetics. Pharmacokinetic parameters for tubular secretion of DPP, as determined by a single-injection renal clearance method, were 21.25 micrograms/mL for the Michaelis-Menten constant and 102.38 micrograms/min for maximum velocity. Coadministration of probenecid decreased the total body clearance of DPP but did not change in the steady-state volume of distribution of DPP. The effect of probenecid concentration on the steady-state renal clearance of DPP was evaluated by continuously infusing probenecid at various rates. The renal clearance of DPP decreased as the probenecid concentration increased, a result indicating that probenecid inhibits the tubular secretion of DPP. However, probenecid did not inhibit the renal secretion of DPP completely, probably because of the existence of probenecid-insensitive transport systems for DPP in the renal proximal tubule. The Michaelis-Menten constant, maximum velocity, and glomerular filtration rate, as calculated with the competitive inhibition model for renal clearance of DPP, correlated well with estimated values after a single intravenous administration, as described earlier. The competitive inhibition constant of probenecid was 15.86 micrograms/mL. PMID- 1432613 TI - Application of a pharmacokinetic model with multiple enterohepatic cycles to a new inotropic drug after infusion and oral administration. AB - A pharmacokinetic model with multiple, unequal, enterohepatic recirculations was developed to fit the experimental data of a new inotropic drug after intravenous infusion and oral administration. Optimized model parameters were used to derive theoretical values of the area under the curves of concentration versus time that were in good agreement with the experimental values. PMID- 1432615 TI - Racemization and intramolecular nucleophilic substitution reactions of ibutilide. AB - The kinetics and mechanisms of the racemization and cyclization reactions of ibutilide are described. The cyclization reaction yields a bell-shaped rate-pH curve consistent with a change in rate-determining step. It is hypothesized that the hydroxyl group leaves to form a carbocation intermediate; this is followed by nucleophilic attack by the amine. This mechanism is supported by kinetic analysis, aniline trapping of carbocation intermediate, and observation of all four stereo-isomers of the resulting quaternary ammonium compound. Whereas racemization can also progress through the carbocation intermediate, a direct SN2 mechanism appears to be the major route for the racemization reaction. PMID- 1432616 TI - Pharmacokinetic analysis of maprotiline and its demethylated metabolite in serum and brain of rats after acute and chronic oral administration of maprotiline. AB - Compartmental model analysis by simultaneous curve fitting was used to ascertain the pharmacokinetic relationship between maprotiline (MAP) and its demethylated metabolite desmethylmaprotiline (DMAP) in the serum and brain of rats after single or multiple oral administrations of MAP. The extent of bioavailability and the fraction metabolized to DMAP after acute oral administration were 0.202 and 0.065, respectively, indicating first-pass metabolism of MAP. Although the estimated transfer rate constants to and from the brain (k(in) and k(out)) of MAP were higher than those of DMAP, the k(in):k(out) ratio for MAP was similar to that for DMAP. These findings indicate the equivalent ability of MAP and DMAP to penetrate into the brain after acute oral administration. The estimated values of bioavailability and fraction metabolized to DMAP increased 2.6 and 1.7 times, respectively, after chronic administration of MAP. These findings are attributable to inhibited distribution in tissue. The k(in) and k(out) values of MAP decreased, whereas those of DMAP showed no marked change. Therefore, the k(in):k(out) ratio for MAP decreased, whereas that for DMAP did not change. These results suggest that the permeability of MAP into the brain might be affected and that of DMAP is not modified by chronic administration of MAP. PMID- 1432617 TI - Determination of pivaloylcarnitine in human plasma and urine by high-performance liquid chromatography with fluorescence detection. AB - A high-performance liquid chromatographic (HPLC) method was developed for the determination of pivaloylcarnitine, one of the major metabolites of pivaloyloxymethyl (+)-(6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2- pentenamido]-3 carbamoyloxymethyl-8-oxo-5-thia-1-azabicyclo[4.2.0] oct-2- ene-2-carboxylate hydrochloride hydrate (S-1108), an oral cephem antibiotic, in human plasma and urine. Fluorescence detection was done with 3-bromomethyl-6,7-dimethoxy-1-methyl 2(1H)-quinoxalinone as the labeling reagent. Pivaloylcarnitine and cyclopropylacetylcarnitine, the internal standard, were selectively fractionated from plasma or urine on a disposable cation-exchange column. Derivatization was completed in 20 min at 40 degrees C in the presence of N,N'-diisopropylethylamine as the catalyst. A column-switching device was used to remove the excess reagent for HPLC analysis. The recovery of pivaloylcarnitine was greater than 98%, and average within-day and between-day coefficients of variation were less than 5% at concentration ranges of 0.05-2 micrograms/mL for plasma and 5-500 micrograms/mL for urine. Detection limits were 0.02 micrograms/mL for plasma and 1 micrograms/mL for urine. The urinary recovery of pivaloylcarnitine was 94% after the administration of S-1108, a result that suggested that S-1108 was almost quantitatively converted to pivalic acid and then conjugated with carnitine. PMID- 1432618 TI - Pharmacokinetic profile of glycyrrhizin in healthy volunteers by a new high performance liquid chromatographic method. AB - An improved high-performance liquid chromatographic method was developed for the quantification of glycyrrhizin and its metabolites in human plasma. The improved method was selective and made it possible to determine precisely glycyrrhizin at levels as low as 500 ng/mL. The pharmacokinetic behavior of glycyrrhizin and its metabolites after oral and intravenous administration of glycyrrhizin to normal subjects was investigated. After oral administration of glycyrrhizin (100 mg) to three normal subjects, the major metabolite of glycyrrhizin (glycyrrhetic acid) appeared in plasma (less than 200 ng/mL), but glycyrrhizin was not found. On the other hand, glycyrrhizin was found in urine, and the amount excreted was 1.1-2.5% of the dose. This finding suggests that glycyrrhizin is partly absorbed in the intact form from the gastrointestinal tract. The concentration of glycyrrhizin in plasma after intravenous administration of glycyrrhizin (40, 80, and 120 mg) showed biexponential profiles during the 24-h period after administration of each dose. The glycyrrhizin metabolites, glycyrrhetic acid and glycyrrhetic acid-3-O glucuronide, were not detected in either plasma or urine. The terminal half-life of glycyrrhizin, the apparent volume of the central compartment, the steady-state distribution volume, and the total body clearance in three dosing experiments were 2.7-4.8 h, 37-64 mL/kg, 59-98 mL/kg, and 16-25 mL/kg/h, respectively. Glycyrrhizin was not detected in plasma after oral administration of the usual therapeutic dose of glycyrrhizin, and no dose dependency of the drug was observed in the dose range of 40-120 mg. PMID- 1432620 TI - Principles and criteria in the development and optimization of topical therapeutic products. PMID- 1432619 TI - Pharmacokinetic analysis of ester prodrugs of valproic acid. AB - The pharmacokinetics of five monoester prodrugs of valproic acid (VPA) were investigated: propyl valproate (P-VPA), butyl valproate (B-VPA), isobutyl valproate (IB-VPA), isoamyl valproate (IA-VPA), and hexyl valproate (H-VPA). In addition, the anticonvulsant activity of these compounds was evaluated and compared with that of VPA and valpromide (VPD). The pharmacokinetics of VPA and its five ester derivatives were determined after intravenous administration of equivalent doses (400 mg of VPA) to six dogs. The five ester prodrugs of VPA were biotransformed to VPA; the biotransformation was complete for P-VPA, B-VPA, and H VPA but was only partial for IB-VPA and IA-VPA. Because of the rapid conversion of the prodrugs to the parent drug, levels of VPA in plasma after administration of the prodrugs peaked at 6-26 min after dosing and did not yield an in vivo sustained-release dosage profile. Of the five ester prodrugs of VPA, only P-VPA demonstrated anticonvulsant activity. P-VPA also was less neurotoxic than VPA and VPD; therefore, it has a better protective index. PMID- 1432621 TI - Molecular connectivity: treatment of the electronic structure of amino acids. AB - A molecular connectivity model of atomic charges on the second-row atoms in alpha amino acids is discussed. A correlation was found between the valence delta (delta v) index from molecular connectivity theory and the charges on atoms that belong to the same class, whereas different classes of carbon atoms had the same slopes on the Q versus sigma v matrix, where Q is the calculated charge distribution. A similar correlation was found for nucleotide bases. PMID- 1432622 TI - Electrochemical determination of partition coefficients of drugs. AB - An electrochemical method for the determination of partition coefficients of drugs that can exist as ions in aqueous solutions is presented. The method involves cyclic voltammetry at the polarizable interface between two immiscible electrolyte solutions. Because n-octanol is an unsuitable solvent for electrochemical purposes, 1,2-dichloroethane, which has electronic properties similar to those of n-octanol, was used in the measurements. The values obtained could be correlated with the values for n-octanol-water partition taken from the literature by an approach based on the linear solvation relationship: log P1 = a log P2 + b; in this relationship, a and b are constants and P1 and P2 correspond to the two different organic and aqueous phase partition equilibria. Furthermore, aqueous diffusion coefficients of drugs were determined from voltammograms. PMID- 1432623 TI - Formation of a tablet: a site and bond percolation phenomenon. AB - The concepts of percolation theory are used to elucidate the formation of a tablet by compression of particulate matter. The process of compaction can be considered as a combination of site and bond percolation phenomena. Because of effects of different particle size and shape of the particles in a powder bed and effects of brittle fracture and plastic flow, moisture content of the powder, and finite size of the tablet, no sharp percolation thresholds are expected. Thus, it is interesting to test the validity of the fundamental equation of percolation theory: the power law X = S(p - pc)q, where X is the system property, S is the scaling factor, p is the site occupation or bond formation probability, and q is the critical exponent. This model is, in certain cases, only rigorously valid close to the percolation threshold (range, [+/- 0.1 pc]). Combination of the Heckel equation with an equation derived earlier for the properties (X) of tensile strength (sigma t) and deformation hardness (P) yields a power law with q = 1, S'(sigma t) = sigma tmax/(1 - pc), and S(P) = Pmax/(1 - pc). With respect to the simplifying assumptions made, the power law agrees well with the experimental results obtained. Substantial improvements in the interpretation of the compression-compaction process are possible with these findings, and some interpretations differ from previous ones in earlier publications. PMID- 1432625 TI - Kinetics of transdermal penetration of an organic ion pair: physostigmine salicylate. AB - Physostigmine salicylate was delivered from a series of solvents consisting of isopropyl myristate, isopropyl alcohol (IPA), and their mixtures across dermatomed human skin. The apparent steady-state fluxes over the time range of the test, obtained separately for physostigmine and its corresponding salicylate, indicate a consistent trend toward higher values for the salicylate in the series tested. The ratios of salicylate fluxes to physostigmine fluxes ranged from 1.1 to 3.34, the higher ratios being obtained at a volume fraction of IPA exceeding 0.7. Ionization of the ion pair at the pH of the hydrated stratum corneum immediately after its partitioning into the membrane, followed by differential diffusion of the species across the membrane, is consistent with the kinetics of penetration. It is proposed that the apparent volume of distribution of physostigmine is larger than that of salicylate and, hence, a smaller concentration difference across the diffusion barrier exists for physostigmine. This hypothesis can explain the lower flux of physostigmine to conform to Fick's first law of diffusion and the assumption of equal molar transfer to the skin of both species. The hypothesis implies that if steady state appears to have been reached for the faster migrating salicylate over the time range tested then the apparent steady state of physostigmine is not a true one. Increasing the salicylate content in one of the donor solutions by eight times over that of physostigmine decreased the saturation concentration of physostigmine but not in its flux. Increasing the physostigmine content by 6.5 times over that of salicylate in the same donor solution did not change either the flux or the salicylate concentration but decreased the permeability coefficient of physostigmine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432624 TI - Relationship of film properties to drug release from monolithic films containing adjuvants. AB - The rate of drug release from a polymeric matrix system was influenced by the physical and chemical properties of the monolithic films. The model drugs, salicylic acid and chlorpheniramine maleate, and two poly(methyl methacrylate) copolymers of different permeabilities (Eudragit RL and Eudragit RS), with and without additional adjuvants, were used to form monolithic matrix films for controlled drug release. Adjuvants, including polyethylene glycols (PEG 400 and PEG 8000) and poly(vinylpyrrolidones) (PVP-K15 and PVP-K90), were incorporated into films of Eudragit RL PM and Eudragit RS PM. The moisture permeation constant, glass transition temperature (Tg), tensile strength, and drug release profiles were determined for each acrylic resin slab to correlate the physicochemical and physicomechanical film properties to observed drug release. Faster rates of drug diffusion were observed with the addition of PEG 400 to the films, because of its plasticizing effect and the resultant increased moisture permeability of the matrix. An exception existed with the Eudragit RL PM film containing salicylic acid where drug-polymer interactions inhibited drug diffusion. The small changes in moisture permeability, Tg, and tensile strength observed with incorporation of the PVPs had an insignificant influence on the dissolution results for salicylic acid from Eudragit RS PM films. Increases in the tensile strength and Tg after addition of PVP to the Eudragit RS PM matrix support the observed decreased rate of diffusion for chlorpheniramine maleate. The pores formed by migration of the hydrophilic adjuvants from the films altered the diffusion kinetics of the matrix, compared with that of the nonporous polymer, when only the antihistamine was present. PMID- 1432627 TI - A time hierarchy-based model for kinetics of drug disposition and its use in quantitative structure-activity relationships. AB - By using the time hierarchy of the processes determining the fate of drugs in biosystems (absorption, transport, distribution, protein binding, and elimination), a one-compartment open model is formulated at a subcellular level for the disposition phase of pharmacokinetics. The resulting disposition function describes the kinetics of the intracellular disposition of drugs as determined by their hydrophobicity, acidity or basicity, affinity to proteins, and rate parameters of elimination. Structure-activity relationships, based on the function with incorporated extrathermodynamic relations, fit the literature data well (fixed-time bioactivity-hydrophobicity profiles, kinetics of microbial degradation of organic compounds, and kinetics of analgesic effects of fentanyl derivatives in rats). Application of the approach, creating a basis for the construction of model-based quantitative structure-time-activity relationship, to biosystems of varying complexity is discussed. PMID- 1432626 TI - Transdermal drug delivery systems of albuterol: in vitro and in vivo studies. AB - In vitro and in vivo experiments were conducted with double- and single-layer albuterol transdermal pads designed for once-a-day application. In the in vitro experiments, dissolution of albuterol from pads and permeation of albuterol through hairless mouse skin were monitored. In the in vivo experiments, pads were applied to the chest area of four female rhesus monkeys (Macaca mulata), and an albuterol aqueous solution was injected into the saphenous vein of the same animals in a crossover design. The amount lost from pads applied to monkeys was monitored by analysis of pad residue. Blood samples were withdrawn at regular intervals and analyzed by a high-performance liquid chromatography-fluorescence method. Skin irritation due to the pad was measured by a modified Draize score test. The amounts released from the two formulations were similar. The amount released was, however, dependent on the technique used and decreased in the following manner: pad dissolution greater than in vivo amount lost from pads applied to monkeys greater than in vitro permeation through hairless mouse skin. The pharmacokinetic parameters determined after intravenous and transdermal administration were as follows: terminal half-life, 2.26 +/- 0.45 h; apparent volume of distribution, 1935 +/- 37.2 mL.kg-1; and total body clearance, 612.0 +/ 118 mL.h-1.kg-1. The average concentrations in serum after application of single and double-layer pads were 44.60 +/- 16.40 and 62.50 +/- 8.00 ng/mL, respectively. Further, the amount lost from pads applied to monkeys correlated with the respective amount absorbed in monkeys, as calculated from the average concentration in serum and clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432628 TI - Solid-state structure of orphenadrine hydrochloride and conformational comparisons with diphenhydramine hydrochloride and nefopam hydrochloride. AB - The solid-state structure of (+-)-orphenadrine hydrochloride [(CH3)2NCH2CH2OCH(o CH3C6H4)(Ph).HCl], a skeletal muscle relaxant drug, was determined by single crystal X-ray diffraction analysis. Orphenadrine hydrochloride gave crystals belonging to the monoclinic P2(1)/n space group, and at low temperature (92 K), the following parameters were found: a = 6.923 (4), b = 7.508 (5), c = 33.22 (3) A, V = 1720 (3) A3, Z = 4, R(F) = 0.109, and Rw(F) = 0.131. Data were collected from poor crystalline material because of the low volume of the needle-shaped crystals (0.025 x 0.025 x 0.15 mm3). A molecular mechanics model was calculated by using an input structure based on atomic coordinates of the crystallographically determined molecular structure. The resulting molecular mechanics model and the structure determined by X-ray crystallography have the same molecular conformation. Whereas both solid-state (+-)-orphenadrine hydrochloride and diphenhydramine hydrochloride [(CH3)2NCH2CH2OCH(Ph)2.HCl] have synclinal N-C-C-O and antiperiplanar NC-C-O-CAr2 torsion angles, the former has a helical arrangement for Ar2CH, as expected, and the phenyl rings in the latter are disposed in a nonhelical, "open-book" arrangement. PMID- 1432629 TI - A compartment model for percutaneous absorption: compatibility of lag time and steady-state flux with diffusion model. AB - The lag times and steady-state flux predicted by a specific case of the compartment model, which was recently proposed to generate finite-dose percutaneous permeation pharmacokinetics, are compared with those predicted by the diffusion model. When the intercompartmental transfer rate constants are defined so that the three statistical moments of the compartmental model (the mean residence times of a drug in the vehicle and that in the skin and the variance of residence time in the vehicle) are identical to those in the diffusion model, the lag times and steady-state flux values predicted by the two models are the same. PMID- 1432630 TI - A theoretical analysis of a new drug delivery system: a cylindrical device with a vertical opening on its surface. AB - A theoretical analysis of a proposed drug delivery device is presented. The device is of cylindrical shape with an opening on its side surface. Analytical expressions for the temporal variations in the amount of drug released and the size of the unreleased portion of the device are derived. The result of numerical simulation reveals that an approximately zero-order mechanism can be obtained, provided that the device is designed appropriately. The applicability of the analytical expressions derived is justified by examining the release of sodium salicylate embedded in polyethylene. The present work is a generalization of analyses suggested previously for some similar devices. PMID- 1432631 TI - Lecithin organogel as matrix for transdermal transport of drugs. AB - Organogels obtained by adding small amounts of water to a solution of lecithin in organic solvents were studied as matrices for the transdermal transport of drugs. Gels obtained from isopropyl palmitate and cyclooctane were used (molar ratios of water to lecithin of 3 and 12, respectively). Preliminarily histological studies showed that the gels have no harmful effect when applied to the skin for prolonged periods. Data relative to the stability of the organogels with time are also presented. Scopolamine and broxaterol were used as model drugs, and the transdermal experiments were done with a Franz diffusion cell and human skin obtained from plastic surgery. The transport rate of scopolamine obtained with the lecithin gels was about one order of magnitude higher than that obtained with an aqueous solution of the drug at the same concentration. In contrast, the transport rates of scopolamine obtained with the microemulsion solution prior to gelation (molar ratio of water to lecithin, 0) were not different from those obtained with the gel. The same variations in transport rates were observed for broxaterol, in which case the flux through the skin was directly proportional to the concentration of drug in the gel. At a concentration of broxaterol of 75 mg/mL in the donor gel, the flux was 47 micrograms.h-1.cm-2. Because preliminary results showed that transdermal transport is successful with amino acids and peptides also, it is concluded that lecithin gels may be efficient vehicles for the transdermal transport of various drugs. PMID- 1432632 TI - Rate-limiting steps in oral absorption of a leucotriene D4 antagonist in the beagle dog. AB - Oral administration of a leucotriene D4 antagonist drug (1) in the Beagle dog at doses of 2, 20, 100, 300, and 800 mg/kg resulted in dose-dependent bioavailability values (4-50%). To understand the dose dependence of the absorption of 1 in the dog, initial rates of absorption of 1, which were estimated from Loo-Riegelman analysis of the concentration in blood data, were analyzed in terms of dissolution and absorption rates. From the Loo-Riegelman plots, the initial rates of absorption of 1 were estimated as 8.2, 41.9, 41.1, 76.1, and 72.8 micrograms.mL-1.h-1, respectively, for the doses given earlier. These data, which indicate leveling of the initial absorption rates at high doses, were consistent with an absorption model in which the dissolution rate is the rate-controlling step in the intestinal absorption of 1 at doses less than 100 mg/kg. The powder dissolution rate of 1 in 17 mM bile salt solution was estimated as 14 and 700 micrograms.mL-1.h-1 for amounts of 1 equivalent to the amounts given to dogs at 2- and 100-mg/kg doses, respectively. After consideration of the volume of distribution and the volume of intestinal fluid in the dog, the value of the initial dissolution rate was much lower than the initial absorption rates at the 2-mg/kg dose. Oral administration of 1 at 2 mg/kg in a 3% polysorbate 80 solution enhanced both the rate and the extent of absorption of the compound. These results confirm the validity of the conclusion that the intestinal absorption of 1 is limited by dissolution rate at low doses. PMID- 1432634 TI - Variability of inversion of (R)-flurbiprofen in different species. AB - The anti-inflammatory activity of 2-arylpropionic acids like flurbiprofen appears to be due to the S enantiomers only. A unique characteristic of the metabolism of this class of drugs is inversion of configuration. The present study examines whether chiral inversion occurs after administration of the optically pure flurbiprofen enantiomers to various species (i.e., dogs, guinea pigs, rats, and gerbils). Concentrations of the enantiomers in plasma were analyzed by a stereoselective high-performance liquid chromatographic assay with a chiral alpha 1-acid glycoprotein column. Pharmacokinetic parameters of the flurbiprofen enantiomers were evaluated with a two-compartment computer model. Inversion of (R)-flurbiprofen to its optical antipode occurred to a variable extent in the dog [fraction inverted (Fi) = 0.39; n = 3] and the guinea pig (Fi = 1.00; n = 3) and to a much lower extent in the rat (Fi = 0.02; n = 3) and the gerbil (Fi = 0.05; n = 3). After intravenous administration of (S)-flurbiprofen to dogs, guinea pigs, rats, and gerbils, (R)-flurbiprofen was not detected in plasma (limit of quantification was 0.05 microgram/100 microL of plasma). PMID- 1432633 TI - Epithelial transport of drugs in cell culture. VII: Effects of pharmaceutical surfactant excipients and bile acids on transepithelial permeability in monolayers of human intestinal epithelial (Caco-2) cells. AB - The effects of anionic (sodium dodecyl sulfate and sodium dioctyl sufosuccinate) and nonionic (polysorbate 80 and polyoxyl 40 hydrogenated castor oil) synthetic surfactants and bile acids (sodium taurocholate, sodium taurodeoxycholate, and sodium taurodihydrofusidate) on epithelial integrity were studied in monolayers of human intestinal epithelial (Caco-2) cells grown on microporous polycarbonate filters. The effects of the surfactants on intracellular enzyme activity, cell monolayer permeability, and morphology were studied. The effects on permeability were studied by two methods: measurements of transport of marker molecules (mannitol and polyethylene glycol) and measurements of transepithelial electrical resistance. All surfactants demonstrated concentration-dependent effects on intracellular enzyme activities, permeability, and morphology. The effects of the anionic surfactants were more pronounced than those of the nonionic surfactants. The effects on transepithelial electrical resistance correlated with intracellular dehydrogenase activity. Fluxes of marker molecules were the most sensitive measure of epithelial integrity. The results indicate that the hydrophilic marker molecules permeate the epithelial monolayers through different pathways at different concentrations of the surfactants. The effects of the surfactants were reversible at intermediate concentrations, even though the morphology of the monolayers had changed. The results agree with published data obtained with experimental animals and indicate that Caco-2 cells can be used to study the concentration-dependent effects of surfactants and other pharmaceutical additives on intestinal epithelial permeability. PMID- 1432635 TI - Synthesis and anti-inflammatory activity of fluorinated phenyl styryl ketones and N-phenyl-5-substituted aryl-3-p-(fluorophenyl) pyrazolins and pyrazoles. AB - Various N-phenyl-5-substituted aryl-3-p-(fluorophenyl) pyrazolins and pyrazoles were synthesized by cyclization of the corresponding 4-(fluorophenyl) styryl and 4-(fluorophenyl) dibromostyryl ketones. These compounds were characterized by elemental analysis and UV, infrared, and nuclear magnetic spectral data. All substituted p-(fluorophenyl) styryl ketones [250 mg/kg orally (po)] possessed anti-inflammatory activity, as reflected by their ability to provide protection (51-70%) against carrageenin-induced edema in rat paw. Indomethacin (10 mg/kg, po) and dehydrozingerone (70 mg/kg, po), used as standard reference drugs, provided 97 and 60% protection, respectively. All compounds (0.20 mM) showed ability to denature bovine serum albumin, as observed in in vitro inhibition studies. Inhibition ranged from 7 to 59% for substituted p-(fluorophenyl) styryl ketones and from 12 to 21% for pyrazoles. No correlation was found between the anti-inflammatory activity of p-(fluorophenyl) styryl ketones or substituted pyrazoles and their effectiveness at inhibiting bovine serum albumin denaturation. The low toxicity of p-(fluorophenyl) styryl ketones was reflected by the dose that was lethal in 50% of the cases tested (2000-2500 mg/kg). PMID- 1432636 TI - Simultaneous spectrophotometric determination in solid phase of aspirin and its impurity salicylic acid in pharmaceutical formulations. AB - We report the simultaneous determination of aspirin and its hydrolysis product, salicylic acid, in solid phase by fluorescence spectrophotometry. Aspirin is often the most labile component in a combination-type analgesic compound. Therefore, its stability is often the initial concern in any formulation screening program. Preliminary screening of a large number of potential formulations can be arduous, because most current methods of analysis generally consist of several steps: extractions or column separations followed by UV, colorimetric, or gas-liquid chromatographic assays. The method proposed here is quite suited to large numbers of assays because it is not time consuming, it is straightforward, and it is not subject to interference from the substances present in the pharmaceutical formulations. In addition, the method is nondestructive, not dependent on the sampling procedure, and, above all, quite sensitive. PMID- 1432637 TI - Preparation of neurotensin analogue-containing poly(dl-lactic acid) microspheres formed by oil-in-water solvent evaporation. AB - This report describes the preparation of injectable microspheres containing a neurotensin analogue (NA), which is a hexapeptide with neurotensin activity. NA, a hydrophilic drug, was successfully entrapped into poly(dl-lactic acid) microspheres prepared by a novel oil-in-water solvent evaporation method. The preparation method was investigated with regard to the partition of NA into the oily phase and the rapid phase separation of the polymer. Successful entrapment was achieved with the following conditions: (1) an alkaline water phase, (2) addition of fatty acid salt in the oily phase, and (3) addition of a water miscible solvent in the oily phase. Under these conditions, NA was completely entrapped into the microspheres at poly(dl-lactic acid):NA molar ratios of greater than 3. PMID- 1432638 TI - Preparation and evaluation of Eudragit gels. IV: Rectal gel preparations for sustained release and avoidance of first-pass metabolism of propentofylline. AB - Formulations of a high-viscosity acrylic resin gel (Eudispert hv) containing propentofylline, a new cerebral microcirculation-improving agent, were prepared and tested for avoidance of the first-pass metabolism of propentofylline through the liver and for sustained release of propentofylline. The absolute bioavailability of propentofylline after oral administration was only 4% in rabbits. The relative bioavailabilities of propentofylline from polyethylene glycol (M(r), 2000) and Witepsol H-15 suppositories were approximately 8- and 16 fold, respectively, compared with oral administration. Furthermore, the absolute bioavailability of propentofylline from Eudispert hv hydrogel and xerogel preparations was approximately 100%. The results indicate that, in principle, drug loss caused by first-pass metabolism may be avoided completely by placing Eudispert hv hydrogel and xerogel formulations in the lower part of the rectum for long periods. PMID- 1432639 TI - Acid-catalyzed hydrolysis of maltosyl-beta-cyclodextrin. AB - Maltosyl-beta-cyclodextrin was hydrolyzed via two pathways in acidic solution: (1) ring opening to give noncyclic oligosaccharides and (2) cleavage of maltose in the branched residue to give glucosyl-beta-CyD and glucose. Ring opening was approximately 2-3 times faster than maltose cleavage because of the multiple hydrolysis sites of the beta-cyclodextrin (beta-CyD) ring (seven glycosidic linkages) compared with only one reaction site of the maltose residue in the branch. Values of the enthalpy and entropy of activation of the hydrolyses were positive and in the range reported for maltose, a result indicating that the hydrolyses proceeded according to the A-1 mechanism (i.e., unimolecular decomposition). The alpha-1,6-glycosidic bond of branched beta-CyDs connecting beta-CyD and branched sugar moieties resisted hydrolysis; this property is a potential pharmaceutical advantage because the parent beta-CyD, which has low aqueous solubility, would not precipitate after hydrolysis. PMID- 1432640 TI - Reversible adsorption of nicotinic acid onto charcoal in vitro. AB - The effects of various factors on the adsorption of nicotinic acid onto and desorption from activated charcoal were investigated in vitro. The affinity of nicotinic acid for charcoal was poor both in acidic and neutral media. Adsorption increased with increasing charcoal:drug ratios and decreasing incubation volume:charcoal ratios. Desorption of nicotinic acid from dried drug-charcoal complexes was investigated in a Sartorius dissolution apparatus. The rate of the rapid, initial desorption depended on the pH and the amounts of charcoal and drug. As equilibrium was reached in the dissolution chamber, the release rate of nicotinic acid decreased slowly, depending mainly on the flow of the medium. Thus, nicotinic acid preadsorbed onto charcoal was released in a sustained manner under "continuous flow" conditions. However, because of the poor affinity for nicotinic acid, charcoal may not be a suitable matrix for sustained release of nicotinic acid. PMID- 1432641 TI - Polarographic study of the photodecomposition of nimodipine. AB - Nimodipine, a calcium antagonist belonging to the dihydropyridine family, produces a well-defined polarographic peak due to the four-electron reduction of the nitro group. This peak was used to track the photodecomposition of nimodipine induced by UV light and daylight. Nimodipine was modified by UV irradiation with degradation following first-order kinetics. A degradation rate constant of 0.099 min-1, with a half-life of 7.78 min, for UV irradiation without a filter was obtained. Furthermore, a quantum yield of 1.32 x 10(-3) molecules/quantum absorbed was measured with a chemical actinometer. The UV degradation product, which was isolated and identified, showed that irradiation of nimodipine causes oxidation of the dihydropyridine ring and transmutation of the nitro group in the nitrobenzene moiety. PMID- 1432642 TI - Pharmacodynamic system analysis of the biophase level predictor and the transduction function. AB - This work deals with the pharmacodynamic problem of relating a drug effect E(t) to an observable pharmacokinetic (PK) predictor variable r(t), which may be a venous and/or arterial drug level, some other PK variable, or a drug infusion scheme. It is proposed that the relationship between E(t) and r(t) may, in many cases, be appropriately modeled as E(t) = N(F(r(t))) [for practical analysis reasons, F(r(t)) is denoted the biophase level, cb(t), the operator F() is accordingly denoted the biophase level predictor (BLP), and N() is denoted the transduction function (TF)]. This work proposes a method for determining the two fundamental components, BLP and TF, that define the E(t)-r(t) relationship. The BLP is determined by a hysteresis minimization (HM) technique with the following features: (1) the method considers errors in both HM variables; (2) the method is suitable for dealing with the important case in which the predictor variable is a drug infusion scheme; (3) the approach is noncompartmental in contrast to the effect-compartment approaches and it does not require a specific structured modeling of the cb(t)-r(t) relationship when dealing with drugs with linear PKs in a general operational sense; and (4) the method makes use of a dimensionless transformation of the hysteresis variable that eliminates numerical scaling problems so that a complex penalty function optimization approach can be avoided. The TF is determined by a cross validation procedure in conjunction with the BLP determined by HM. The method is demonstrated using pharmacodynamic data for several drugs, considering both concentration-based and drug input-based r(t) values. The significance of the information obtained from the determined BLP and TF is discussed, including the concepts of equilibration dynamics and overloading. The limitations and potential problems of the methodology are discussed. PMID- 1432643 TI - Stereoselective pharmacokinetics of a novel uricosuric antihypertensive diuretic in rats: pharmacokinetic interaction between enantiomers. AB - 5-Dimethylsulfamoyl-6,7-dichloro-2,3-dihydrobenzofuran-2-carboxyli c acid (DBCA), a promising uricosuric, diuretic, and antihypertensive agent, was administered intravenously to rats. The levels of DBCA in plasma and the areas under the curve of concentration versus time (AUC values) of the S(-)-enantiomer were higher than those of the R(+)-enantiomer. Total body clearance was significantly greater for the R(+)-enantiomer. This stereoselective elimination was due to a difference in the nonrenal clearance, which seemed to reflect hepatic metabolism or biliary excretion. Hepatic metabolism seemed more likely because AUC and the amount of urinary excretion of the N-monodemethylated metabolite of DBCA were greater for the R(+)-enantiomer. The plasma had higher free fractions of the S(-)-enantiomer, a result suggesting that this enantiomer is distributed more readily to the tissues, including the liver. This result indicates that protein binding was not responsible for the stereoselective metabolism of (R)-(+)-DBCA. Although there was no difference in the renal clearances of the enantiomers, the renal clearance of free (R)-(+)-DBCA exceeded that of the S(-)-enantiomer, a result indicating the preferential excretion of the R(+)-enantiomer into the urine. Comparison of the pharmacokinetics of individual enantiomers after intravenous administration of each enantiomer or its racemate showed that the enantiomers interact with one another; dosing with racemate delayed the elimination of each enantiomer because of mutual inhibition of hepatic metabolism and renal excretion for (R)-(+)-DBCA and of renal excretion for (S)-(-)-DBCA. PMID- 1432644 TI - Effects of chronic ethanol ingestion on tissue elimination-phase kinetics of procainamide in rats. AB - The effects of chronic ethanol ingestion on the pharmacokinetics of procainamide in various tissues were studied. Ethanol-treated rats received ethanol at 4 g/kg/day for an initial 7 days and then at 8 g/kg/day for the subsequent 21 days; control rats received isocaloric sucrose. After a single intravenous dose, the semilogarithmic procainamide concentration-time profiles observed in hearts and kidneys of both groups of rats were similar to the previously reported biexponential profiles of procainamide concentration in blood. This finding indicates a rapid distribution equilibrium of drug in both blood and these highly perfused tissues. The profiles of drug concentration in thigh muscle and fat of both groups of rats exhibited a drug-uptake phase during the initial 25-min period followed by a monoexponential decline in drug concentration. For all tissues, the slopes (beta values) of the curves of the drug concentration versus time were calculated on the basis of elimination-phase data, except for fat of control rats where the predominant elimination phase was not discernible. The beta values in hearts and thigh muscles of ethanol-treated rats were significantly higher than those in the corresponding tissues of control rats. These results are evaluated in light of previously reported effects of the same ethanol treatment on the distribution pharmacokinetics and the steady-state partition coefficients of the drug in these tissues. Possible mechanisms are proposed to account for these effects on the basis of the known diverse effects of chronic ethanol ingestion on the cellular compositions of individual organs and tissues. PMID- 1432645 TI - Use of scavenging oxygen-derived free radicals to protect the rat against aspirin and ethanol-induced erosive gastritis. AB - Oxygen-derived free radicals are cytotoxic and produce tissue damage. The effect of the radical scavengers allopurinol and dimethyl sulfoxide (DMSO) on aspirin- and ethanol-induced acute gastric mucosal injury was studied in the rat. Orogastric instillation of aspirin at 200 mg/kg produced, after 4 h, gastric mucosal injury in 30% of rats without pyloric ligation [score, 3.1 +/- 0.8 mm2, mean +/- standard error of the mean (SEM); n = 10] and in 80% of rats with this ligation (score, 10.4 +/- 1.2 mm2, mean +/- SEM; n = 10). Gavage with 1 mL of 2 or 5% allopurinol or DMSO at 24 h before and again just before aspirin administration completely protected rats with or without pyloric ligation against injury. Orogastric instillation of ethanol (1 mL of a 40% solution) produced, after 1 h, gastric mucosal injury in all rats with or without pyloric ligation (24.1 +/- 1.7 and 14.1 +/- 1.3 mm2, respectively, mean +/- SEM; n = 10). Gavage with 1 mL of 5% allopurinol or DMSO at 24 h before and again just before ethanol administration completely protected rats with or without pyloric ligation against injury. Protection against the aspirin- and ethanol-induced injury was not associated with any significant effect on the H+ output. The results suggest that oxygen-derived free radicals are directly implicated in the mechanism of aspirin- and ethanol-induced acute gastric mucosal injury and that scavenging these free radicals protects against injury by maintaining the integrity of the gastric mucosa. PMID- 1432646 TI - Measurement of haloperidol in human breast milk by high-performance liquid chromatography. AB - A high-performance liquid chromatographic method was developed for the assay of haloperidol in human breast milk. The method involves rapid extraction of haloperidol and chromatography with a reversed-phase C18 column and a mobile phase of phosphate buffer (pH 4.0):acetonitrile (70:30, v/v). Moperone was used as the internal standard. Haloperidol and moperone were detected with ultraviolet detection at 254 nm. The sensitivity was 5 ng/mL of milk, and the standard curve was linear in the concentration range 5-250 ng/mL. The average interassay coefficient of variation for samples with drug in the concentration range 25-125 ng/mL was less than 8.8%. The absolute recovery of haloperidol by the method was greater than 94.4%. No interference with endogenous substances in human milk was observed. The method was used to determine haloperidol levels in breast milk from patients undergoing chronic haloperidol treatment. PMID- 1432647 TI - Isolation and biological evaluation of potential cancer chemopreventive agents from ambrette musk residue. AB - Two nitroaromatic compounds, 1-(1,1-dimethylethyl)-3,5-dimethyl-2,4 dinitrobenzene (1) and 1-[4-(1,1-dimethylethyl)-2,6-dimethyl-3,5 dinitrophenyl]ethanone or musk ketone (2), were isolated from ambrette musk residue, which is widely used in the food and cosmetics industry. The ability of 1 and 2 to induce increased activity of the detoxifying enzyme glutathione S transferase was tested in A/J mice. Enzyme induction in the cytosols of liver, forestomach, lung, colon, and small intestinal mucosa was determined. Biological evaluation revealed that both compounds exhibit high activity as glutathione S transferase inducers in liver and small intestinal mucosa. The effects of 1 and 2 on the levels of acid-soluble sulfhydryl in the five mouse tissues were also determined. Both compounds slightly elevated sulfhydryl levels in the small intestinal mucosa but significantly decreased the sulfhydryl levels in the other tissues. Because the ability of anticarcinogenic compounds to induce an increase in the detoxifying enzyme activity correlates with their tumor inhibitory activity, 1 and 2 may be potential cancer chemopreventive agents. PMID- 1432648 TI - A new method for the estimation of the aqueous solubility of organic compounds. AB - Using a semiempirical quantum chemical method (AM1), various properties (dipole moment, charge distribution, geometrical parameters, etc.) of 331 compounds were calculated. Various linear functions of these properties and their combinations were fitted to reproduce experimental aqueous solubilities. An 18-parameter function was derived that is reasonably simple, yet appears to be able to describe the aqueous solubilities of a wide range of organic compounds. The parameter set is essentially the one used in a recent similar study of octanol water partition coefficients. The derived equation has important predictive value. PMID- 1432649 TI - Pharmacokinetics of glycyrrhizin after intravenous administration to rats. AB - A simple high-performance liquid chromatographic method was developed to study the pharmacokinetics of glycyrrhizin in the rat after bolus intravenous administration at a dose of 20, 50, or 100 mg/kg. The decline in the concentration of glycyrrhizin in plasma was generally biexponential at each dose, but the terminal disposition became much slower as the dose was increased. A greater-than-proportional increase in the glycyrrhizin concentration in plasma was observed with an increase in the dose, a result suggesting a dose-dependent glycyrrhizin disposition. The disposition of drug in plasma at each dose fitted well to a two-compartment pharmacokinetic model. The apparent total body clearance decreased significantly with increases in the dose. On the other hand, the apparent distribution volume after intravenous administration was unaffected by the dose. The results indicate that the pharmacokinetics of glycyrrhizin is nonlinear. PMID- 1432650 TI - Synthesis and anti-inflammatory activity of 3-(benzylideneamino)coumarins in rodents. AB - A series of substituted 3-(benzylideneamino) coumarins was synthesized and evaluated for anti-inflammatory activity against carrageenan-induced edema in rats. Halogenated derivatives 4g and 4c, at oral doses of 100 mg/kg, showed 75 and 60% antiedmatous activity, respectively (phenylbutazone antiedematous activity, 58%). The analgesic activity of 4g and 4c, based on inhibition of acetic acid-induced writhing in mice (67 and 62%, respectively, at oral doses of 100 mg/kg) was comparable with that of aspirin (58%). However, these derivatives were devoid of antipyretic activity and showed low activity against adjuvant induced arthritis. PMID- 1432651 TI - Warfarin sodium. Practitioner beware. AB - The use of warfarin sodium in the US has increased dramatically over the last 40 years. Warfarin sodium or Coumadin is the most popular oral anticoagulant used in the US. The podiatric physician frequently encounters patients taking this agent and therefore needs to understand its potential impact. This article will familiarize the reader with the history, pharmacology, clinical applications, side effects, and frequent drug interactions encountered with warfarin sodium. PMID- 1432652 TI - Rotational scarf (Z) osteotomy bunionectomy for correction of high intermetatarsal angles. AB - A modification of the scarf osteotomy bunionectomy is described. The modification involves a change in the movement of the osseous fragments from lateral transposition to lateral rotation of the metatarsal head fragment around a stationary axis at the metatarsal base. Rotation of the distal fragment in this manner allows greater than 50% transposition and, therefore, higher intermetatarsal angle corrections can be obtained as compared to a transpositional scarf osteotomy. The configuration of the scarf osteotomy is more stable to the stress of weightbearing than the closing base wedge osteotomy, and this modification can provide a useful alternative to closing base wedge osteotomy for the correction of severe hallux valgus deformity. PMID- 1432653 TI - Treatment of lower extremity infections in diabetics. AB - The infected diabetic lower extremity has enjoyed a surge in popularity in the medical literature. There have been numerous papers outlining classification systems for ulcer depth, surgical approaches, and microbiology. Discussions on antibiotic use have usually been directed toward therapy of the "diabetic foot infections" as a group, without regard to differences in severity and location of these infections. These infections can vary from the most superficial of processes to a severe life- and limb-threatening sepsis. The author presents a review of the processes involved in the diabetic lower extremity infection and suggests a classification system for selection of empiric antibiotic therapy based on the severity of the infection. PMID- 1432654 TI - Effect of rearfoot posts in reducing forefoot forces. A single-subject design. AB - The purpose of this study was to assess the effectiveness of a semirigid foot orthosis with a varus wedge on forefoot vertical forces in a 24-year-old female with a compensated rearfoot varus deformity. The results of this study indicate that the use of total contact semirigid foot orthoses reduces the forefoot force time integral during walking, whether a rearfoot varus wedge was or was not used. The authors recommend that total contact construction of the foot orthoses be considered when a reduction of the forces acting on the forefoot is the goal of treatment. PMID- 1432655 TI - Current diagnostic and radiographic assessment of tendo Achillis rupture. AB - The literature is replete with current clinical evaluation techniques of tendo Achillis rupture. An overview of the etiologies, diagnosis, radiographic evaluation, and treatment modes, either surgical or conservative, is presented with a brief description of two lesser known techniques: the knee flexion examination and needle test. PMID- 1432656 TI - Onychia of a macronychia in congenital aphalangia. PMID- 1432658 TI - Kaposi's sarcoma of the foot. A case presentation. PMID- 1432657 TI - Ciprofloxacin in the treatment of Mycobacterium fortuitum infection of the peroneal tendons. A case report. AB - In the case reported, M. fortuitum was sensitive in vitro to amikacin, erythromycin, tobramycin, and ciprofloxacin. Because the patient did not respond to long-term therapy with amikacin and erythromycin, an experimental antibiotic, ciprofloxacin, was tried. Only after extensive surgical debridement and 2 1/2 months of oral ciprofloxacin therapy was the infection eradicated and wound healing obtained. The authors conclude that a wound that has reopened, but remains indolent, exudes a clear, serous drainage and responds poorly to antibiotics should suggest a possible mycobacterial infection. Combination antibiotic therapy is recommended because of the high rate of relapse and development of resistance to drugs. Extensive surgical debridement of all infected tissue remains the primary treatment. The therapeutic value of ciprofloxacin and other newer antibiotics in the treatment of mycobacterial infection is promising. PMID- 1432659 TI - Management of complications associated with an excision of a lipoma from the ankle. AB - This case study demonstrates the following: close proximity of lipoma to underlined skin can compromise circulation; the size of the lipoma and the resulting redundant skin after the incision can lead to fluid development and impede the healing process; and a patient who is noncompliant and stands or walks excessively after the excision of a lipoma can cause buildup of a hematoma, which can compromise the incision site. Lipomas associated with the foot or ankle are rarely symptomatic. When they do cause pain and are surgically treated, possible complications because of their size and location must be considered. Finally, these complications could have been avoided if the redundant skin had been excised and a Penrose drain inserted to eliminate excess fluid buildup. Also, better communication should have been maintained with the patient during the entire postoperative course. PMID- 1432660 TI - Podiatric literature. PMID- 1432661 TI - Combined surgery for glaucoma and cataract. PMID- 1432662 TI - Loop memory of posterior chamber intraocular lenses of various sizes, designs, and loop materials. AB - Looped intraocular lenses (IOLs) fixate by exerting centripetal pressure on the ocular tissues. The ability of the flexible loops to maintain pressure depends on their rigidity (i.e., resistance to flexion) and their "memory" (i.e., ability to restore original configuration after a long period of compression). We studied the memory of 30 different posterior chamber IOLs, with loops made of polypropylene (PP) and poly(methyl methacrylate) (PMMA), of various diameters, styles, and designs. The lenses were inserted into plastic wells, 9.5 mm in diameter, and immersed in water (37 degrees C) for one month. They were then placed on an open plate and allowed to re-expand for one month. Loop memory was calculated as the difference in diameter between the initial (pretest) measurement and measurements taken during the compression and release periods. The results showed that short (12.0 to 12.5 mm) IOLs had relatively better memory than longer (13.5 to 14.0 mm) IOLs. Those with PP loops expanded more and for longer periods than those comparable size and design with PMMA loops. One-piece, all-PMMA lenses exhibited the best loop memory. These lenses have the high rigidity of the PMMA material and the good memory of the design. Thus, the total IOL diameter can be reduced to 12.0 mm while providing long-term constant pressure on the capsular bag to maintain stable fixation. PMID- 1432663 TI - Comparison of shape recovery ratios in various intraocular lens haptics. AB - Since understanding the mechanical properties of intraocular lens (IOL) haptic materials can minimize decentration after surgery, we have examined shape recovery ratios of various intraocular lens haptics (polypropylene [PP], polyvinylidene fluoride [PVDF], extruded poly(methyl methacrylate) [PMMA]) currently on the market under conditions that approximate clinical use. The results using various Ascon lens-holding forceps and compression tests, during which the lenses were held in a cylindrical holder for seven days, one month, and three months, indicated that PVDF haptics had better shape recovery capability than PP and extruded three-piece PMMA haptics. PMID- 1432664 TI - Aqueous humor analysis after Nd:YAG laser capsulotomy with the laser flare-cell meter. AB - Using the laser flare-cell meter (Kowa FC-1000), we conducted a prospective study analyzing the effect of Nd:YAG posterior capsulotomy on the quantity of aqueous particles, aqueous flare, and intraocular pressure in 65 eyes (58 patients). Aqueous particles increased at six hours, followed by flare rise which was significant at 18 hours after capsulotomy. Only 22 eyes (34%) had a significant flare rise over prelaser values. Anti-inflammatory therapy was necessary in only one patient. The mean intraocular pressure value did not rise significantly after capsulotomy. Acute intraocular hypertension (AIOHT) (> 7 mm Hg increase) occurred between three and six hours after laser therapy in 12 patients (19%), was related in time to particle rise, and always responded to a single dose of acetazolamide. Acute intraocular hypertension was strongly correlated with elevated aqueous particles (P < .0001) and somewhat correlated with flare rise (P < .036), but was not correlated with the intraocular lens position (bag or sulcus fixation). Our findings strongly suggest that trabecular meshwork clogging by debris generated by the capsulotomy is the mechanism at the origin of AIOHT. PMID- 1432665 TI - Effect of preoperative YAG laser anterior capsulotomy on the incidence of posterior capsule opacification: ten year follow-up. AB - One hundred twenty-two patients, who were followed for ten years, had bilateral extracapsular cataract surgery with implantation of J-looped posterior chamber lenses between 1980 and 1981. On the first eye an anterior capsulotomy was performed with a pico-second YAG laser 12 to 20 hours before surgery; on the second eye a capsulotomy was performed manually at the time of surgery. Four of the eyes (3.27%) with laser capsulotomies had opacified posterior capsules after ten years; 61 of the eyes (50.00%) with manual capsulotomies had opacified capsules that had to be opened with a YAG laser. PMID- 1432666 TI - Effect of neodymium:YAG laser photodisruption on intraocular lenses in vitro. AB - Poly(methyl methacrylate) (PMMA) based intraocular lenses (IOLs) such as injection-molded PMMA and lathe-cut PMMA IOLs and soft IOLs such as silicone and poly(hydroxyethyl methacrylate)(polyHEMA) IOLs were tested for vulnerability to Nd:YAG laser photodisruption. The laser beam was focused on the posterior surface and inside of the IOLs in balanced salt solution. Cracks and central defects with radiating fractures were observed in PMMA IOLs; blistered lesions and localized pits were observed in silicone and polyHEMA IOLs, respectively. A molten edge surrounding the large hole, which was an indication of the thermal effect of the laser, was observed in the injection-molded PMMA while only a minute lesion was found in the polyHEMA IOL which contained 38% water. The size of the superficial damage of the IOL increased as the power of laser irradiation increased and PMMA IOLs showed greater damage than soft IOLs (P < .05). PMID- 1432667 TI - Antiplatelet therapy and cataract surgery. AB - To gain information about patients who continue antiplatelet therapy while having cataract surgery, we performed a prospective, nonrandomized study. Twenty-four of 60 phacoemulsification procedures were performed on patients who were receiving medications with antiplatelet activity prior to surgery and who continued to receive the medications for the duration of the study. The remaining 36 procedures were performed on patients who received no medications with antiplatelet activity prior to surgery. One patient in the antiplatelet therapy group had a limited peribulbar hemorrhage, and one patient not receiving antiplatelet therapy had a postoperative hyphema. Postoperative subconjunctival hemorrhages were more common in the antiplatelet therapy group (P = .001). No patient in the antiplatelet therapy group had late postoperative complications. No differences in postoperative visual acuity or intraocular pressure were observed between the groups. Our results demonstrate that phacoemulsification and posterior chamber intraocular lens implantation can be performed without serious complications in some patients who continue to use antiplatelet therapy. However, our sample sizes were too small to determine whether such therapy is associated with any increased risk of rare but serious hemorrhagic complications. PMID- 1432668 TI - Fluorescent viscoelastic enhancement. AB - By inserting an Erreger 485 exciter filter into the operating microscope, translucent yellow Healon (sodium hyaluronate) transforms into a brilliant opaque green viscoelastic. We have developed this technique and termed it "fluorescent viscoelastic enhancement." Using the technique, we demonstrated that the time required to remove Healon from the anterior chamber after intraocular lens insertion varies. Healon is usually aspirated quickly, in less than 17 seconds. Otherwise it traps behind the intraocular lens and requires more time for irrigation/aspiration (I/A) and manipulation of the I/A tip. Fluorescent viscoelastic enhancement minimized I/A time, reducing excess turbulence and manipulation in the anterior chamber, and thus may reduce corneal endothelial cell loss. This study also demonstrated that fluorescent viscoelastic enhancement prevented postoperative intraocular pressure rise, compared to the conventional removal of clear Healon. Fluorescent viscoelastic enhancement assures the surgeon that a large amount of Healon is not left behind. PMID- 1432669 TI - Visual outcome following complicated extracapsular cataract extraction. AB - In a prospective study of 1,597 consecutive extracapsular cataract extractions (ECCE), we review 49 cases complicated by capsular or zonular rupture with or without vitreous loss. The ECCEs were divided into two groups depending on the type of intraocular lens (IOL) implanted. In Group A, whose patients received an anterior chamber lens, we found a significantly (P < .05, t-test) worse postoperative visual acuity than in Group B whose patients received a posterior chamber lens. We therefore suggest that in the presence of a capsular tear and vitreous loss, one should try to implant a posterior chamber lens rather than an anterior chamber lens to obtain as good a visual acuity as possible. PMID- 1432670 TI - Combined trabeculectomy, cataract extraction, and foldable lens implantation. AB - The efficacy of foldable silicone intraocular lenses in combined glaucoma/cataract surgery was retrospectively analyzed in 19 consecutive operations. Preoperatively all patients were receiving medical treatment for glaucoma; 21% had intraocular pressures above 21 mm Hg despite the medical therapy. Postoperatively, reduction of intraocular pressure to 21 mm Hg or less was achieved in 84% of eyes, with 58% requiring no antiglaucoma medications. Mean improvement of Snellen visual acuity was 4.9 lines; 84% of eyes achieved a final acuity of 20/40 or better. Median follow-up was 59 weeks (range 25 to 88 weeks). Thirteen eyes (68%) had a filtration bleb present when last examined. These preliminary results suggest that foldable silicone IOLs are an effective alternative to poly(methyl methacrylate) lenses in combined glaucoma/cataract surgery. PMID- 1432671 TI - Incidence of postoperative posterior capsular opacification with types of senile cataracts. AB - The most frequent postoperative complication in extracapsular cataract surgery is opacification of the posterior capsule. The purpose of this study was to correlate the frequency of capsular opacification with each kind of senile cataract. A total of 566 eyes with cataracts were studied. They had been operated on between 1980 and 1990 using the extracapsular, intercapsular, and phacoemulsification techniques. Our results confirm that senile complete cataracts (mature cataracts) had a significantly lower tendency to produce postoperative capsular opacification than other cataract types (nuclear, cortical, posterior subcapsular). PMID- 1432672 TI - Panoramic specular microscopy of lens epithelial cells in the postoperative pseudophakic eye. AB - Using the Konan-Keeler specular microscope, panoramic specular microscopy covering almost one quadrant of the anterior capsule was performed. Regional changes in the retained lens epithelial cells were recorded and compared simultaneously. The nearer the rim of the anterior capsular opening, the greater the decrease of cell density, increase of average cell size, and variety of cell size. The results indicate that the first postoperative changes in lens epithelial cells following phacoemulsification with subsequent capsular bag intraocular lens implantation occur in the area close to the anterior capsular opening, with subsequent changes in peripheral areas. PMID- 1432673 TI - Refractive bifocal intraocular lens and pupillary diameter. AB - To assess the relationship between pupillary diameter and focusing for distance and near vision with the refractive bifocal intraocular lens (IOL), we studied visual acuity for far and near distance, near point, and depth of focus with normal pupillary movements and after pharmacological miosis and mydriasis (pilocarpine 2% and phenylephrine 10% eyedrops, respectively) in 20 patients implanted with an IOLAB refractive bifocal IOL. Pharmacological miosis and mydriasis did not change far and near visual acuity values from the values with normal pupillary diameter. After pharmacological miosis, the near point position and the width of the depth of focus were unchanged. After pharmacological mydriasis, near point distance was unchanged but depth of focus dropped in a statistically significant manner (P < .01). We concluded that the pupillary diameter alone cannot produce distance or near vision focusing. The choice depends on the brain's preference. Pupillary diameter increases the quality of vision through the blur circles mechanism. PMID- 1432674 TI - In vitro adhesion of Pseudomonas aeruginosa and Staphylococcus aureus to surface passivated poly(methyl methacrylate) intraocular lenses. AB - Bacterial attachment to intraocular lenses (IOLs) can be a cause of infectious endophthalmitis following cataract surgery. In this study, Pseudomonas aeruginosa and Staphylococcus aureus adhered in vitro to untreated poly(methyl methacrylate) (PMMA) and to surface passivated PMMA lenses. The IOLs were placed in bacterial suspensions (1 x 10(7) cfu/ml) in vitro. Significantly fewer S. aureus attached (P < .05) to the normal PMMA IOLs (4,535 +/- [SD] 3,052 bacteria/mm2) and to passivated PMMA IOLs (8,720 +/- 10,040 bacteria/mm2) than did P. aeruginosa (normal PMMA: 67,808 +/- 45,070 bacteria/mm2, passivated PMMA: 85,795 +/- 70,647 bacteria/mm2). The differences in bacterial attachment to surface passivated IOLs and to untreated PMMA lenses were not significant. PMID- 1432676 TI - Optical testing and inspection methodology for modern intraocular lenses. AB - A method of in vitro optical performance evaluation of intraocular lenses (IOLs) is discussed. The IOLs are tested in the eye cell, which is designed to be optically equivalent to the theoretical eye model. The eye cell is a combination of a wet cell and the optical element (the "conjugation lens") that converges a beam of light, similar to the action of the cornea in the theoretical eye model. The eye cell is designed so the spatial frequency scale (modulation transfer frequency [MTF] testing), expressed in terms of line pairs per millimeter (linear scale), equals the scale produced by the theoretical eye model. The most common way to express spatial frequencies in visual science is in line pairs per degree or cycles per degree (angular scale). The problem with in vitro testing is that the corresponding angular scale varies with the dioptric power of the conjugation lens. This paper provides a simple method of mapping the angular scale of the eye cell onto the theoretical eye model, allowing a comparison with clinical results as well as with MTFs measured in different eye cells. All corresponding formula for calculating the eye cell optical characteristics are provided. PMID- 1432675 TI - Cellular reaction following cataract surgery with implantation of the heparin surface-modified intraocular lens in rabbits with experimental uveitis. AB - The inflammatory response after cataract surgery and intraocular lens (IOL) implantation was studied in rabbits with endotoxin-induced uveitis. On days 1, 3, 7, 14, and 30 postoperatively the rabbits were sacrificed and the number of white blood cells in the aqueous humor and cellular deposits on the IOLs were estimated. On days 14 and 30 the rabbits also had slitlamp examination to study the clinical outcome of the surgery. At day 1 after lens extraction and IOL implantation, the number of white blood cells in the aqueous humor was significantly lower (P < .05) in eyes with heparin-surface-modified (HSM) IOLs (795.2 +/- 262.9; mean +/- SEM) than in eyes with poly(methyl methacrylate) (PMMA) lenses (1386.5 +/- 247.9). No differences were seen at day 3, 7, 14, or 30 postoperatively. The choice of IOL material had no effect on the amount of cell deposits on the IOL surface or on clinical parameters such as anterior synechias, posterior synechias, fibrosis, and posterior capsular opacification. There was a trend toward a greater number of cellular deposits on the PMMA lenses, but this was not statistically significant. This study provides further evidence of improved biocompatibility of the HSM PMMA lens, as demonstrated by a decreased acute inflammatory response. PMID- 1432677 TI - Down slope sculpting. AB - A method of sculpting and fracturing that greatly enhances the efficiency and safety of in-situ nuclear fracturing (nucleofractis) techniques is presented. By nudging the nucleus of the lens inferiorly, sculpting can be accomplished very deep in the upper part of the lens to facilitate early and efficient fracturing. The benefits, advantages, and safety of this "down slope" sculpting technique are described. PMID- 1432678 TI - Simplified insertion technique for the SI-26NB intraocular lens. AB - Inserting the 13 mm SI-26NB intraocular lens is a challenging task complicated by the need to tuck the modified C-configuration haptics within a folded optic. This step causes undue stress on the haptic and may result in asymmetrical distortion and subsequent decentration. Excluding this step simplifies the technique, as well as decreases the degree of acute angle stress on the haptic as it is passed through the scleral tunnel. PMID- 1432679 TI - Mechanics of capsulorhexis. AB - Continuous (central, circular) curvilinear capsulorhexis (CCC), first introduced by Gimbel and Neuhann, has become increasingly popular, especially for endolenticular phacoemulsification with intracapsular intraocular lens implantation. The principles of simple mechanics are used to facilitate teaching the procedure and to reduce the incidence of complications. A safe and simple method of performing CCC based on these principles is described. PMID- 1432680 TI - Consultation section. Increasing and significant difficulty with reading and driving at night. PMID- 1432681 TI - Effect of captopril and the nonpeptide angiotensin II antagonists, SK&F 108566 and EXP3174, on renal function in dogs with a renal artery stenosis. AB - Treatment with an angiotensin converting enzyme (ACE) inhibitor can result in acute renal failure in patients with a renal artery stenosis. In the present study the effects of the selective nonpeptide angiotensin II antagonists, SK&F 108566 ((E)-alpha-[[2-Butyl-1-[(4-carboxyphenyl)methyl]-1H-imidazol-5-yl] methylene]-2-thiophenepropanoic acid) and EXP3174 (2-n-Butyl-4-chloro-1-[(2'-(1H tetrazol-5-yl)-biphenyl-4-yl) methyl]imidazole-5-carboxylic acid hydrochloride) (the active metabolite of DuP 753, losartan) were compared with the ACE inhibitor, captopril, in the anesthetized dog which had been uninephrectomized and the remaining renal artery clamped to reduce renal blood flow (RBF) by approximately 50%. All three agents resulted in dose-dependent reductions in mean arterial pressure (MAP), glomerular filtration rate (GFR) and RBF. The maximum responses to captopril and SK&F 108566 were similar with MAP, RBF and GFR all decreasing approximately 30%. EXP3174 also resulted in decreases in GFR and RBF of approximately 30%; however, there was a smaller (approximately 17%) decrease in MAP. The data indicate that the possible bradykinin enhancing activity of ACE inhibitors may not provide any moderating activity of ACE inhibitor-induced reduction in GFR observed in dogs with a renal artery stenosis. PMID- 1432682 TI - Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks. AB - Passive avoidance performance was impaired in young rats by scopolamine (1.0 mg/kg) or by nucleus basalis magnocellularis lesions and in aged rats (24-26 months old). FR121196[N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide+ ++], a newly introduced cognitive enhancer, ameliorated the failure in memory retention with bell-shaped dose-response curves in doses ranging from 0.1 to 10 mg/kg. Similar dose-response curves also were obtained with methamphetamine (0.1 10 mg/kg), whereas physostigmine (0.01-1.0 mg/kg) attenuated the amnesia in scopolamine-treated rats, but hardly affected that in nucleus basalis magnocellularis-lesioned or aged rats. In radial arm maze tasks, behavioral indices of spatial memory, such as first correct choices and number of errors, were impaired by an injection of scopolamine (0.5 mg/kg) or by lesions of the medial septum or fimbria-fornix. FR121196 ameliorated the scopolamine-induced memory deficit with a bell-shaped dose-response curve, whereas methamphetamine had the opposite effect. These two drugs had little effect on memory deficits brought about by medial septum or fimbria-fornix lesioning, whereas physostigmine ameliorated these deficits in scopolamine-treated and medial septum-lesioned rats, but not in fimbria-fornix-lesioned rats. Behavioral studies using Animex demonstrated that FR121196, in contrast with methamphetamine, does not increase locomotor activities in rats up to a dose of 10 mg/kg. These results are discussed in relation to the cholinergic and dopaminergic mechanisms of memory. PMID- 1432683 TI - L-dopa induces opposing effects on pain in intact rats: (-)-sulpiride, SCH 23390 or alpha-methyl-DL-p-tyrosine methylester hydrochloride reveals profound hyperalgesia in large antinociceptive doses. AB - The present study shows that during the time course of the action of single doses, L-dopa induces multiphasic opposing effects on pain, recorded as vocalization during the presentation of electrical stimulation applied to the tail of normal rats. This indicates that two or more functional systems contribute to produce the net response. A small dose (15 mg/kg) of L-dopa facilitates pain slightly, whereas larger doses (100-200 mg/kg) can produce an antinociceptive effect following an initial hyperalgesia. Moreover, profound hyperalgesia is revealed by either dopamine (DA) D1 and D2 receptor blockade by means of SCH 23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetra hydro-1H- 3-benzazepine hydrochloride] or (-)-sulpiride, respectively, as well as after a reduction of the presynaptic synthesis of catecholamines after pretreatment of the animals with the tyrosine hydroxylase inhibitor alpha-methyl DL-p-tyrosine (alpha-MPT). The enhancement of L-dopa's hyperalgesic effect after SCH 23390 treatment is maximal already at the onset of the effects, whereas (-) sulpiride or alpha-methyl-DL-p-tyrosine precipitates the hyperalgesia after a certain temporal delay during defined phases of the time course of the effects of large L-dopa doses. The D1 receptor agonist (+)-SKF 38393 potentiates both the hyperalgesic and antinociceptive effects of 100 mg/kg of L-dopa. It is suggested that L-dopa's net effect on pain is modulated from concentration-dependent, opposing effector systems involving both DA stimulatory and inhibitory receptor mechanisms. At high dosing, activation of D2 receptors enhancing DA functional activity produces an antinociceptive response that normally outweighs the hyperalgesia, but this effect becomes dissociable with inhibition of central DA activity. PMID- 1432684 TI - Effects of chronic treatment with ethanol on the development of cross-tolerance to other alcohols and pentobarbital. AB - The development of cross-tolerance to various alcohols and pentobarbital was examined in ethanol (EtOH)-treated mice. Chronic EtOH treatment (dosage rising in steps from 3.5-4.5 g/kg i.p. daily during a 23-day period) produced tolerance to its hypnotic effect. Such tolerance was seen as a reduction in the duration of loss of righting reflex (LRR), as well as higher blood EtOH levels at the offset of LRR, in EtOH-treated mice as compared to saline-treated controls. Cross tolerance was shown by shifts in dose-response curves for the LRR induced by n propanol and t-butanol. Such treatment, however, did not confer functional cross tolerance to n-butanol and pentobarbital. Because n-butanol and pentobarbital are more lipid-soluble, whereas EtOH, n-propanol and t-butanol have low degrees of lipid solubility, the development of cross-tolerance among these sedative hypnotic drugs might be related to their relative degrees of lipid solubility. PMID- 1432685 TI - 5-Hydroxytryptamine 1a receptor agonists block prepulse inhibition of acoustic startle reflex. AB - Presentation of a nonstartling stimulus (prepulse) 100 msec before a startle eliciting auditory stimulus (pulse) reduces startle reflex amplitude in mammals. Prepulse inhibition of acoustic startle reflex is smaller in schizophrenics than in nonschizophrenics, a phenomenon that has been hypothesized to reflect sensorimotor gating deficits underlying schizophrenic psychosis. Five 5 hydroxytryptamine1a (5-HT1a, serotonin) receptor agonists: 8-hydroxy-2-(di-n propylamino) tetraline (8-OHDPAT), 5-methoxydimethyltryptamine, buspirone, gepirone and ipsapirone, were tested for effects on prepulse inhibition and startle reflex amplitude in rats. All five agents reduced prepulse inhibition at doses that had no effect on startle reflex amplitude or motor activity. Reduction of prepulse inhibition by 8-OHDPAT was antagonized by (-)propranolol, a 5-HT1a receptor antagonist, and partially by haloperidol, a dopamine D2 receptor antagonist, but not by ketanserin or methysergide, 5-HT2 receptor antagonists. 8 OHDPAT did not reduce prepulse inhibition in subjects pretreated with reserpine or tetrabenazine to deplete neuronal amines, but interpretation of this result is complicated because reserpine and tetrabenazine given alone reduced prepulse inhibition. The results indicate that 5-HT1a receptor agonists block prepulse inhibition of acoustic startle reflex, possibly via dopaminergic mechanisms. PMID- 1432686 TI - Tolerance to the cataleptic effect of the N-methyl-D-aspartate (NMDA) receptor antagonists in pigeons: cross-tolerance between PCP-like compounds and competitive NMDA antagonists. AB - The effects of chronic administration of phencyclidine (PCP) or CGS 19755 (cis-4 phosphonomethyl-2-piperidine-carboxylic acid) on the cataleptic effects of N methyl-D-aspartate (NMDA) receptor antagonists were studied in pigeons. PCP, a channel blocker of the NMDA receptor complex, or CGS 19755, a competitive NMDA antagonist, was administered i.m. to separate groups of pigeons each day. Tolerance developed to the cataleptic effects in both PCP- and CGS 19755-treated pigeons. PCP tolerance was characterized initially by 5-fold rightward shift and, with an increased chronic PCP dose, a complete downward shift of the PCP dose effect curve. CGS 19755 tolerance was indicated by a 10-fold rightward shift of its dose-cataleptic effect curve. Cross-tolerance was obtained from PCP to other PCP-like compounds including dizocilpine (MK 801), ketamine, dextrorphan, 1-(2 thienyl)-cyclohexyl-piperidine and [(+)-SKF 10047] [(+)-N-allyl-normetazocine] as well as to the competitive NMDA antagonist, CGS 19755. Cross-tolerance also developed from CGS 19755 to another competitive NMDA antagonist, CGP 40116 [D-(E) 2-amino-4-methyl-5-phosphono-3-pentenoic acid] as well as to PCP-like compounds. The pharmacological selectivity of tolerance was evident because there was equal sensitivity to etomidate or pentobarbital in tolerant and nontolerant pigeons. The symmetric cross-tolerance between PCP-like compounds and competitive NMDA antagonists suggests the cataleptic effects of the two classes of NMDA antagonists are probably mediated via a similar mechanism of inhibition of neurotransmission at the NMDA excitatory synapse. PMID- 1432687 TI - Prolonged stimulation of bovine adrenal chromaffin cells with arachidonic acid and prostaglandin E2 increases expression of the proenkephalin gene and the secretion of [Met5]-enkephalin. AB - The effects of long-term exposure of bovine adrenal medullary chromaffin (BAMC) cells to arachidonic acid (AA) and prostaglandin E2 (PGE2) on [Met5]-enkephalin (ME) secretion and expression of the proenkephalin A (proENK) gene were studied. Treatment with various concentrations of AA or PGE2 for 24 hr increased the secretion of ME in a concentration- and time-dependent manner. At high concentrations (10-100 microM), but not low (1-3 microM), AA significantly increased ME secretion by 1 hr. In contrast, the onset time for increase of ME secretion by PGE2 was 3 hr after exposure. The magnitude of increase in ME secretion in the presence of AA or PGE2 continued to increase with time. However, intracellular ME levels in AA- or PGE2-treated cells were not significantly different from that of controls, indicating that elevated levels of ME secretion into the media may be a result of increased biosynthesis of ME. In addition, AA or PGE2 increased proENK mRNA level in a concentration- and time-dependent manner. The onset time for the increase in proENK mRNA in response to PGE2 was 6 hr after exposure. The treatment of BAMC cells with 20 microM cycloheximide (a protein synthesis inhibitor) inhibited both the increased secretion of ME and proENK mRNA level induced by AA and PGE2 in a time-dependent manner, indicating that the delayed secretion of ME and the increase in proENK mRNA level induced by AA and PGE2 require protein synthesis. Indomethacin (a cyclooxygenase inhibitor, 10 microM) effectively inhibited AA-induced responses, whereas 10 microM nordihydroguaiaretic acid (a lipoxygenase inhibitor) was inactive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432688 TI - Effects of in vivo and in vitro administration of morphine sulfate upon rhesus macaque polymorphonuclear cell phagocytosis and chemotaxis. AB - The effects of morphine administration were evaluated upon the polymorphonuclear (PMN) cell activities of rhesus macaques. Sixteen animals were used in the study. Seven macaques were treated with saline and nine animals were administered morphine in the form of morphine sulfate, following a control period of saline injections. The dosage regime was initiated at 1 mg of morphine sulfate per kg of b.wt., 3 times daily, with incremental steps to a stable dose of 5 mg/kg, 3 times daily. PMN cells prepared from morphine-treated animals showed a marked, transient reduction in their ability to kill ingested yeast blastospores, although the ingestive capacity of the PMN cells was not impaired. PMN cells prepared from three of the nine morphine-treated animals showed a transient reduction in chemotaxis toward a complement-derived chemotactic factor. In vitro studies on PMN cells prepared from morphine-naive animals suggested that the killing activity and the chemotaxis of the cells were reduced by treatment with 50 pM morphine sulfate, but not with 50 fmol of morphine sulfate. PMID- 1432689 TI - Platelet-activating factor stimulates arachidonic acid release and enhances thromboxane B2 production in intact fetal rat brain ex vivo. AB - The ability of brain preparations from 20-day-old rat fetuses to synthesize eicosanoids in the presence of platelet activating factor (PAF) was investigated. A rise (49%) in thromboxane B2 (TxB2; the stable thromboxane A2 metabolite) was observed after 30 min in the presence of 0.6 microM PAF. Repetitive administration of PAF did not rise TxB2 production above a certain level, suggesting desensitization. 1-O-alkyl, sn-glycero-3-phosphocholine (lyso-PAF) at 0.6 microM had no effect, whereas selective PAF antagonists, i.e., BN52021, BN50739 and BN50727, or indomethacin, a general cyclooxygenase inhibitor, blocked completely TxB2 synthesis. The calcium ionophore A23187 (10 microM) stimulated production of TxB2, prostaglandin E2 and 6-keto-prostaglandin F1 alpha eicosanoids, whereas extracellular calcium deprivation did not impair eicosanoid release. The effects of PAF and A23187 on TxB2 synthesis were not additive and were not dependent on extracellular calcium. Chelation of intracellular Ca++ by Fluo-3/AM reduced production of TxB2 and prostaglandin E2 eicosanoids. Fluo-3/AM also blocked effectively PAF-dependent TxB2 release, indicating that production of TxB2 was almost entirely dependent on free intracellular calcium levels. PAF dependent changes in brain phospholipids, prelabeled with [3H]arachidonic acid, were examined. One hour after in vivo injection of the isotope, fetal brains were removed and incubated in vitro for 30 min with carbamyl-PAF. Radioactivity in arachidonic acid and diglyceride fractions increased (35% and 30%, respectively), whereas radioactivity in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol decreased. BN50726 antagonist abolished the effect of PAF. The radioactivity in poly-phosphoinositides was diminished (30-40% decrease) after PAF addition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432690 TI - Effects of various serotonin receptor subtype-selective antagonists alone and on m-chlorophenylpiperazine-induced neuroendocrine changes in rats. AB - Administration of m-chlorophenylpiperazine [m-CPP, a serotonin (5-HT) agonist] to rats increases plasma concentrations of prolactin and corticosterone. Pretreatment with various doses of ritanserin (5-HT1C/5-HT2 antagonist), ICS 205 930 and MDL-72222 (5-HT3 antagonists), iodocyanopindolol or CG361A (beta adrenoceptor antagonists) and spiperone (5-HT1A/5-HT2 antagonist) did not attenuate m-CPP-induced increases in plasma concentrations of prolactin. In contrast, pretreatment with various doses of metergoline (5-HT1/5-HT2 antagonist), propranolol (beta adrenoceptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT1C sites), mesulergine and mianserin (5 HT1C/5-HT2 antagonists) attenuated m-CPP-induced increases in plasma prolactin. On the other hand, m-CPP-induced increases in corticosterone concentrations were attenuated only by pretreatment with a low dose of mianserin and a high dose of spiperone. When administered without m-CPP, metergoline, mesulergine, ritanserin, ICS 205-930 and high doses of mianserin, spiperone and propranolol increased plasma corticosterone secretion. On the other hand, none of the antagonists used in the present study, except spiperone, had any significant effect on plasma prolactin secretion. These findings suggest that m-CPP-induced prolactin secretion is mediated by stimulation of 5-HT1C receptors while corticosterone secretion may be mediated either by an antagonistic effect at 5-HT3 receptor subtype or by nonserotonergic mechanisms. Alternatively, enhancement of corticosterone secretion by the 5-HT antagonists when administered alone may be responsible for their failure to block m-CPP-induced corticosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432691 TI - Functional analysis of brain dopamine systems in a genetic mouse model of Lesch Nyhan syndrome. AB - The Lesch-Nyhan syndrome is a neurogenetic disorder caused by congenital deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). The disorder is characterized by prominent neurobehavioral abnormalities which appear to result in part from dysfunction of striatal dopamine systems. HPRT-deficient (HPRT-) mutant strains of mice have been produced as animal models for this syndrome, but these animals exhibit none of the neurobehavioral abnormalities seen in Lesch-Nyhan patients. The present studies describe the behavioral responses of three strains of mice carrying one of two mutations in the HPRT gene to agents which interact with brain dopamine systems. HPRT- mice are more sensitive than age- and sex-matched littermates to the motor-activating properties of dopamine-releasing agents (amphetamine, amfonelic acid and methylphenidate), but not dopamine uptake inhibitors (GBR 12909 and nomifensine). The enhanced sensitivity of the HPRT- mice to the dopamine-releasing agents is not caused by dopamine receptor supersensitivity, because the HPRT- mice do not show enhanced motor responses to the direct D1/D2 dopamine receptor agonist apomorphine or to the selective D1 dopamine receptor agonist SKF 38393. The function of regulatory dopamine autoreceptors, as assessed by suppression of spontaneous motor activity by low doses of R(-) propylnorapomorphine, also appears normal in the HPRT- mice. Biochemical analysis shows that the HPRT- mice have significantly lower levels of dopamine (-45%), but normal levels of tyrosine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine in the caudoputamen. In contrast to the deficit in caudoputamen dopamine, no deficits were noted in the accumbens of the HPRT- mice. These results indicate the existence of an inherent abnormality in the dopamine systems in the brains of HPRT- mice, despite their apparently normal spontaneous behavior. PMID- 1432692 TI - Motor impairments after methamphetamine-induced neurotoxicity in the rat. AB - Methamphetamine is a psychomotor stimulant which, given in high doses, produces neurodegenerative changes in the dopamine and serotonin systems. This study was designed to assess motoric deficits in the rat following a high-dose regimen of methamphetamine. Long-Evans male rats received either four injections of saline or methamphetamine (12.5 mg/kg, every 2 hr), a dose sufficient to produce 45 and 36% reductions in striatal dopamine and serotonin, respectively. Before treatment, subjects were trained to perform one of the following motor tasks: one way active avoidance, inhibitory avoidance, rotorod or the balance beam. After recovery, performance under base-line and drug challenge conditions revealed that methamphetamine treatment caused significant deficits in active avoidance performance (24% increase in response latency) and balance beam performance (2- to 3-fold increase in footfalls), but had no effect on inhibitory avoidance or rotorod performance. Administration of l-dopa (100 mg/kg) significantly improved the methamphetamine-treated subjects' performance on the balance beam, but had no effect on the control subjects' performance. The methamphetamine-treated subjects exhibited a significant decrease in sensitivity to the effects of fenfluramine in comparison to the controls on both the rotorod and active avoidance tasks. We conclude that high-dose methamphetamine treatment produces long-lasting motor deficits associated with chronic reductions of striatal dopamine and serotonin. These data and the utility of the motor tasks are discussed in reference to a laboratory model of Parkinson's disease. PMID- 1432693 TI - Interactions between zinc and spermidine on the N-methyl-D-aspartate receptor complex: clues to the mechanism of action of 1,10-bis(guanidino)decane and pentamidine. AB - This study investigated the mechanism of action of two novel, noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor using [3H]dizocilpine binding to rat brain membranes. Pentamidine and 1,10(bisguanidino)decane (BG10) inhibited [3H]dizocilpine binding in the concentration range of 1 to 100 microM, as did Zn++ and the competitive polyamine antagonist arcaine. The action of each of these agents was sensitive to the addition of spermidine to the assay. However, only arcaine interacted with spermidine in a competitive fashion. Spermidine decreased the apparent affinity of Zn++ and also increased the Hill slope of the Zn++ inhibition curves. BG10 and pentamidine inhibition of [3H]dizocilpine binding was less sensitive to spermidine. Calcium had similar effects to spermidine on the inhibition of [3H]dizocilpine binding by Zn++, arcaine, pentamidine and GB10, but was less potent than spermidine. Treating membranes with diethylpyrocarbonate, a histidine-modifying reagent, decreased the apparent affinity of Zn++ by more than 4-fold while having very modest effects on the actions of BG10, pentamidine and arcaine. In addition, Zn++ failed to slow the dissociation of [3H]dizocilpine in diethylpyrocarbonate-treated tissue, whereas the action of BG10 and pentamidine was qualitatively unaffected. These data show that the effects of BG10 and pentamidine on the NMDA receptor are complex and may involve more than one binding site for each drug. In addition, this study shows that the action of Zn++ on the NMDA receptor is modulated by polyamines. Finally, the mechanism of action of pentamidine and BG10 cannot be attributed to an action at the Zn++ recognition site. PMID- 1432694 TI - Amiloride-sensitive lithium reabsorption in rats: a micropuncture study. AB - It has been suggested that in sodium-restricted rats lithium is being reabsorbed in the collecting tubule, and that such reabsorption can be prevented by amiloride. We studied these options in rats by means of cortical micropuncture. Indeed, an important fraction of the filtered lithium (10.5%) was reabsorbed beyond the early distal tubule in sodium-restricted rats. Amiloride infusion abolished this reabsorption. The dosage used did not affect the reabsorption of water, sodium and lithium in the proximal tubule, and also did not change the reabsorption of water and sodium in the loop segment. However, the reabsorption of lithium in this segment tended to be higher during amiloride (P = .06), and the delivery of lithium to the early distal puncture site was significantly less (26.1 +/- 1.2%) than in the control rats (31.4 +/- 1.8%, P < .05). The reason for this apparent increase in lithium reabsorption in the loop segment is not clear. Interestingly, amiloride increased urine flow and decreased urine osmolality. The mechanism underlying this effect needs further exploration. We conclude that in sodium-restricted rats lithium reabsorption beyond the early distal tubule level occurs. Lithium clearance data therefore underestimate end-proximal delivery under these conditions. Lithium reabsorption beyond the early distal tubule can be prevented by amiloride treatment. However, because amiloride may stimulate lithium reabsorption further upstream, lithium clearance data obtained during amiloride infusion may still underestimate end-proximal delivery of water and sodium. PMID- 1432695 TI - Potentiation of adriamycin toxicity by ethanol in perfused rat liver. AB - Adriamycin, which has a quinone nucleus, damages periportal regions of the lobule in perfused rat liver in an oxygen-dependent manner, presumably by redox cycling. Because redox cycling requires reducing equivalents, we investigated whether ethanol, which generates NADH via alcohol dehydrogenase, would increase hepatotoxicity due to concentrations of adriamycin which by themselves were not toxic in perfused rat liver. Perfusion with adriamycin (100 microM) alone did not significantly alter oxygen uptake or cell death evaluated by release of lactate dehydrogenase or uptake of trypan blue. In contrast, oxygen uptake due to adriamycin was increased about 35 mumol/g/hr and lactate dehydrogenase release was elevated to values around 240 U/g/hr in the presence of ethanol (10 mM). As expected, ethanol increased NADH fluorescence detected from the liver surface due to reduction of NAD+ in a concentration-dependent manner (half-maximal effect = ca. 1 mM). The increase in NADH fluorescence due to ethanol and the stimulation of oxygen uptake due to adriamycin had similar dependencies on ethanol concentration. Upon infusion of adriamycin, oxygen uptake increased concomitantly with a decrease in NADH fluorescence, most likely due to utilization of NADH. The half-maximal change in both processes also occurred with concentrations of ethanol around 1 mM. Furthermore, methylpyrazole (4 mM), an alcohol dehydrogenase inhibitor, prevented the increase in NADH fluorescence due to ethanol as well as the stimulation of oxygen uptake due to adriamycin in the presence of ethanol. Ethylhexanol, another agent which increased NADH, also potentiated oxygen uptake due to adriamycin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432696 TI - An experimental paradigm for investigating the role of endogenous adenosine/A1 receptor interactions in vivo. AB - The purpose of the present study was to develop a pharmacological method for determining in the rat in vivo whether endogenous adenosine participates in a given process via activation of A1 adenosine receptors. In anesthetized rats, A1 receptors were activated by infusing the highly selective A1 receptor agonist N6 cyclopentyladenosine, and A2 receptors were stimulated by infusing the highly selective A2 receptor agonist CGS21680C. The bradycardic response to N6 cyclopentyladenosine and the hypotensive response to CGS21680C were used to assess A1 receptor and A2 receptor activation, respectively. After control responses to these purinergic agonists were elicited, animals were given infusions for several hours of either vehicle or one of six dosage levels of FK453 (a potent, selective, nonxanthine A1 receptor antagonist), one of three dosage levels of FR113452 (the S-enantiomer of FK453) or one of seven dosage levels of DPCPX (a potent, selective, xanthine A1 receptor antagonist). Antagonists were infused for > 4 hr, and at various times during the infusions, bradycardic and hypotensive responses to N6-cyclopentyladenosine and CGS21680C, respectively, were reassessed. Both FK453 and DPCPX were highly potent A1 receptor antagonists in vivo, and complete inhibition of bradycardic responses to N6-cyclopentyladenosine were obtained with 3 and 1 micrograms/kg/min, respectively. FR113452 was a very weak antagonist and only slightly reduced bradycardic responses to N6-cyclopentyladenosine at 100 micrograms/kg/min. In vivo FK453 and DPCPX were > 300 and 1000 times selective for the A1 receptor, respectively, compared with the A2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432697 TI - Decreased plasma cholinesterase activity enhances cocaine toxicity in mice. AB - The illicit use of cocaine continues in epidemic proportions. Despite the incidence of life-threatening complications from cocaine use, little is known of the individual determinants of cocaine toxicity. In vitro analysis demonstrating that cocaine is poorly metabolized by the serum of patients with low plasma cholinesterase (PCh) activity (succinylcholine sensitivity) led to the hypothesis that altered PCh activity might modulate cocaine toxicity. An in vivo mouse model was created to test this theory. Mice were pretreated s.c. with either parathion [a mixed plasma and red blood cell cholinesterase (RBCCh) inhibitor], tetraisopropyl pyrophosphoramide (a selective PCh inhibitor) or placebo, and cholinesterase activity was determined at 24 hr. Incremental doses of i.p. cocaine were administered in a controlled and blinded fashion, and lethality was observed. Ten mg/kg s.c. parathion produced a mean suppression of 68 +/- 9 and 61 +/- 8% of PCh and RBCCh activity, respectively. One mg/kg s.c. tetraisopropyl pyrophosphoramide produced a mean suppression of 78 +/- 3 and 9 +/- 8% of PCh and RBCCh activity, respectively. Each pretreatment produced a statistically significant increase in cocaine lethality throughout the dose-response curve. Our results suggest that PCh activity is an important determinant of cocaine toxicity. This effect appears to be independent of either RBCCh activity or manifestations of organophosphate intoxication. PMID- 1432698 TI - Propylbenzilylcholine mustard has greater specificity for muscarinic m2 receptors than for m3 receptors present in cerebellar granule cell culture from rat. AB - Both muscarinic m2 receptors that inhibit adenylyl cyclase and m3 receptors that stimulate the hydrolysis of inositol phospholipids are expressed in cerebellar granule cells. In order to determine whether a reserve population of either of these receptors is present in this cell culture, the irreversible muscarinic receptor antagonist, propylbenzilylcholine mustard (PBCM), was used at different concentrations to bind various proportions of available muscarinic receptors. After pretreating the cell cultures with low concentrations of PBCM (< 1 nM), the muscarinic m2 receptor-mediated response decreased. Higher concentrations of PBCM (1-3 nM) were needed to reduce the muscarinic m3 receptor-mediated response. These results suggested that either a reserve population of muscarinic m3 receptors is present or that PBCM shows greater specificity for muscarinic m2 receptors. Because the muscarinic m2 receptor is a 66 kDa protein, whereas the muscarinic m3 receptor is a 92 kDa protein, these receptors can be separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis after being labeled with [3H]PBCM. PBCM appears to specifically bind the 66 kDa m2 receptor at concentrations lower than those required to bind to the 92 kDa m3 receptor. A linear correlation was found between the increased binding of [3H]PBCM to each receptor and the proportional loss of that receptor-mediated response. Thus, a reserve population of either muscarinic m2 or m3 receptors does not appear to exist in cerebellar granule cells. These studies also show that PBCM has greater affinity for the muscarinic m2 receptor than the muscarinic m3 receptor. PMID- 1432699 TI - Cardiovascular responses to cocaine are initially mediated by the central nervous system in rats. AB - Cocaine produces a pressor response reportedly resulting from both potentiation of peripheral catecholamine activity and a centrally mediated sympathoexcitation. In the present study we sought to differentiate the central nervous system and peripheral contributions to the hemodynamic effects of cocaine. In conscious rats, cocaine (5 mg/kg i.v.) produced a pressor response with two distinct components consisting of a brief, substantial increase in mean arterial pressure (MAP) associated with hindquarters and mesenteric vasoconstriction followed by a sustained, modest response associated with mesenteric vasoconstriction and bradycardia. Pentolinium (7.5 mg/kg i.v.) or adrenal demedullation attenuated the peak increase in MAP by attenuating increases in mesenteric and hindquarters vascular resistance, but did not affect the sustained increase in MAP. Methyl atropine (0.5 or 1 mg/kg i.v.) pretreatment reduced the cocaine-induced increase in systemic vascular resistance and enhanced the hindquarters vasodilation during the sustained MAP response. In contrast, adrenal demedullation abolished the hindquarters vasodilation. The bradycardic response was prevented by pentolinium and reduced by methyl atropine. Sympathetic nerve activity was reduced dramatically after cocaine or procaine administration for several minutes in conscious and in chloralose-anesthetized rats. In several anesthetized rats, the sympathoinhibition was preceded by a brief (3-8 sec) increase in renal sympathetic nerve activity. Procaine or cocaine produced little change in cortical cerebral blood flow as estimated by using a laser Doppler flowmeter. These data suggest that cocaine produces an initial, brief centrally mediated sympathoexcitation, but the sustained, modest pressor response is dependent upon peripheral actions that are diminished by baroreflex activation. PMID- 1432700 TI - Polymorphism of dextromethorphan metabolism: relationships between phenotype, genotype and response to the administration of encainide in humans. AB - The polymorphism of dextromethorphan and encainide metabolism is genetically determined and is related to the activity of hepatic CYP2D6. In order to examine the relations between CYP2D6 phenotype, genotype and the electrocardiographic response to the oral administration of encainide, 110 healthy subjects were studied. Metabolic ratios were calculated in urine after oral administration of 40 mg of dextromethorphan and in plasma obtained 2.5 h after oral administration of 50 mg of encainide. Encainide-induced electrocardiographic changes were measured 2.5 h after oral administration of the drug. Genotype was determined in 52 subjects. Results showed that phenotype, either extensive or poor metabolizer, for CYP2D6-dependent metabolism could be identified from the dextromethorphan metabolic ratio calculated in urine, from the encainide metabolic ratio calculated in plasma and from the genotype. However, despite the fact that the changes in atrioventricular (PR) and intraventricular (QRS) conduction times produced by encainide were different in extensive and poor metabolizer subjects and correlated with CYP2D6 activity, the electrocardiographic response was never 100% specific and sensitive for the identification of either phenotype. Moreover, genotypic identification of heterozygous and homozygous extensive metabolizer subjects did not predict CYP2D6 activity, as determined by dextromethorphan and encainide metabolic ratios, or encainide response, as determined by intraventricular and atrioventricular changes. Thus, CYP2D6 activity does not fully predict the electrocardiographic effects of encainide, and genotype, as determined in our study, cannot replace the determination of metabolic ratio in predicting CYP2D6 activity and encainide response in extensive metabolizer subjects. PMID- 1432701 TI - Effect of pinacidil on the membrane electrical activity of guinea pig detrusor muscle. AB - The effects of pinacidil on the guinea pig detrusor smooth muscle membrane were studied to investigate the electrophysiological mechanisms by which this drug relaxes smooth muscle tissue and, thus, might be of value in the treatment of detrusor instability. Pinacidil (> or = 3 x 10(-7) M) hyperpolarized the membrane in a concentration-dependent manner, with a reduction in spontaneous spike discharges. The membrane hyperpolarization induced by pinacidil was consistently associated with an increase in membrane ionic conductance. Glybenclamide (10(-6) M) completely inhibited the membrane hyperpolarization induced by pinacidil (up to 10(-5) M). Membrane hyperpolarization with pinacidil was consistently greater in a low-K+ solution, and it decreased in the presence of a high-K+ solution, compared with that measured in normal Krebs solution. Pinacidil consistently suppressed carbachol-induced depolarization of the membrane, with a reduction in the frequency of spontaneous action potentials. Glybenclamide (10(-6) M) did not inhibit the effect of pinacidil on increased action potential frequency induced by carbachol but blocked the membrane hyperpolarization induced by pinacidil (10( 5) M). In addition, the amplitude and maximum velocity of depolarization of carbachol- and current-induced action potentials were significantly decreased by pinacidil in the presence of glybenclamide. These results suggest that pinacidil blocks action potential generation in detrusor smooth muscle by inducing membrane hyperpolarization secondary to an increase in K+ permeability. Pinacidil, at high concentrations (> or = 10(-5) M), might block action potentials by inhibiting the voltage-sensitive Ca++ influx independently of hyperpolarization of the membrane. These mechanisms might be of benefit therapeutically in relaxation of unstable detrusor contractions. PMID- 1432702 TI - Ontogeny of N-methyl-D-aspartate-induced current in cultured hippocampal neurons. AB - The ontogeny of the N-methyl-D-aspartate (NMDA) subtype of glutamatergic receptor/ion channel was studied by examining whole cell currents evoked by NMDA in cultured hippocampal neurons 1 to 30 days after plating of cells from 18- to 20-day-gestation rat fetuses. We observed a maturation-dependent increase in conductance, compatible with an increased density of NMDA receptors, which is in agreement with previous binding data. The whole cell currents evoked by NMDA (10 100 microM) in the presence of glycine (1-100 microM) had two components that contributed to the peak amplitude. The first was a rapidly decaying current (fast component) and the second a slowly decaying current (slow component), their ratio depending upon glycine concentration. The EC50 values for glycine were 1.8 and 0.3 microM for the fast and slow components of the current, respectively. The quantitative analysis of these components indicated the existence of two distinct glycine sites, which differ in their affinity for glycine. The fast component originates from the action of glycine at the site with lower affinity. Moreover, the ratio of the fast to the slow component was also dependent on the time lapsed after plating of the fetal hippocampal neurons. The slow component became more predominant and the fast component less predominant along with cell maturation in culture, a phenomenon which reflects a change in the ratio of high- to low affinity glycine binding sites. In addition, studies on Zn2+ gave further evidence of a change in the NMDA receptor/channel properties related to maturation of the cultured neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432703 TI - Developmental change of the inhibition by lead of NMDA-activated currents in cultured hippocampal neurons. AB - The inhibition of N-methyl-D-aspartate (NMDA)-activated current in cultured fetal rat hippocampal neurons by Pb2+ was investigated at various stages of cell development. Pb2+ selectively inhibited NMDA currents recorded from young cultured neurons. In the first week of culture, Pb2+ showed the most prominent inhibition, which was gradually attenuated in the following weeks. Pb2+'s action was selective for NMDA- as opposed to either kainate- or quisqualate-induced currents. The current-voltage relationship for NMDA-induced currents in the presence of Pb2+ revealed that the effect of this cation was voltage-independent, which suggested that the site of interaction of Pb2+ with the NMDA receptor/channel is located outside the membrane electric field. Single channel studies showed that Pb2+ reduced the frequency but not the lifetime of the NMDA activated single channel currents. Further evaluation of the mechanism of action of Pb2+ on the NMDA receptor demonstrated that this cation is a noncompetitive antagonist of both NMDA and glycine. We have demonstrated that the NMDA-induced whole cell currents change along with cell development, and the effects of Pb2+ are also dependent upon age of culture. The NMDA-induced currents in cultured rat hippocampal neurons had two components, one that decayed rapidly and another that decayed slowly. The fast component was clearly observed at concentrations of glycine higher than 1 microM, whereas the slow component reached its maximum amplitude at the glycine concentration of 1 microM. Moreover, the rapidly decaying component of NMDA-evoked whole cell currents was predominant in young cultured neurons, and its contribution to the total current was reduced in old cultured neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432704 TI - Biotin delivery to brain with a covalent conjugate of avidin and a monoclonal antibody to the transferrin receptor. AB - The OX26 mouse monoclonal antibody to the rat transferrin receptor undergoes transcytosis through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo, owing to high concentrations of transferrin receptor on the BBB. This property allows the OX26 antibody to serve as a brain drug transport vector. To simplify coupling of therapeutics to the OX26 antibody, the present studies examine the use of the avidin/biotin system to promote coupling of biotin and biotinylated drugs to brain transport vectors. The OX26 antibody was affinity purified from ascites fluid and was covalently coupled via a thioether linkage to avidin, and the conjugate was purified to homogeneity by gel filtration fast protein liquid chromatography. The biotin binding capacity of the avidin-OX26 conjugate was measured, and 2.3 biotin binding sites per avidin OX26 (1:1) conjugate were detected. Transcytosis through the BBB of [3H]biotin bound to either unconjugated avidin or to the avidin-OX26 conjugate was measured with an internal carotid artery perfusion/capillary depletion technique. [3H]Biotin bound to the avidin-OX26 conjugate was transported through the BBB at rates that equaled the rate of transcytosis of the unconjugated OX26 antibody. The clearance from plasma of [3H]biotin bound to the avidin-OX26 conjugate approximated the rate of clearance of the unconjugated OX26 antibody, and not the rate of clearance of [3H]biotin bound to avidin, which was cleared from plasma at much faster rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432705 TI - GTP-binding protein involvement in membrane currents evoked by carbachol and histamine in guinea-pig ileal muscle. AB - 1. Single smooth muscle cells obtained by enzymic dispersion of the longitudinal muscle layer of guinea-pig ileum were used for recording membrane currents under whole-cell voltage clamp in response to carbachol (100 microM, unless otherwise stated) or histamine (100 microM) applied extracellularly. 2. At a holding potential of 0 mV, a transient outward current was evoked by carbachol and histamine. Responses to the two agonists were very similar in size and time course to the current response to caffeine (10 mM). The response to carbachol was virtually absent in the presence of histamine, and vice versa. Caffeine was without effect in the presence of either of these agonists. Inclusion of EGTA (10 or 20 mM) in the pipette abolished the responses to carbachol, histamine and caffeine. Thus, the outward current responses were considered to represent opening of Ca(2+)-activated K+ channels in response to a massive release of Ca2+ from the same stores by these three agents. 3. An inward current was evoked by carbachol and histamine, but not by caffeine at a holding potential of -40 mV, which was considered to represent opening of cationic channels. The carbachol induced inward current was much longer in duration and larger in size than the histamine-induced inward current. 4. Inclusion of GDP beta S (2 mM) in the pipette abolished the inward and outward current responses to histamine, but inhibited only part of those to carbachol. 5. When the holding potential was held at 0 mV with inclusion of GTP gamma S (0.1-1 mM) in the pipette, spontaneous transient outward currents appeared immediately after break-through but disappeared a few minutes later. Under these conditions, caffeine (10 mM) was almost without effect, suggesting that GTP gamma S had released Ca2+ stores. When the holding potential was held at -40 mV and GTP gamma S (0.1 or 0.2 mM) was present in the pipette, an inward current developed a few minutes after break through. During the GTP gamma S-induced inward current, application of carbachol or histamine produced no further inward current. However, when 0.01 mM-GTP gamma S was included in the pipette solution, carbachol- and histamine-induced inward currents were potentiated. 6. Pretreated with 2-5 micrograms/ml pertussis toxin (PTX) did not change noticeably the outward current responses to carbachol and histamine, but abolished or markedly reduced the inward current responses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432706 TI - Mitochondrial function in type I cells isolated from rabbit arterial chemoreceptors. AB - 1. In this, and the accompanying paper (Duchen & Biscoe, 1992), we test the hypothesis that the oxygen sensitivity of mitochondrial electron transport forms a basis for transduction in the carotid body, the primary peripheral arterial oxygen sensor. We here describe for isolated type I cells the changes in autofluorescence of mitochondrial NAD(P)H that accompany changes in PO2. 2. NAD(P)H autofluorescence (excitation, 340-360 nm; emission peak, 450 nm) increased with anoxia, reflecting a rise in the NAD(P)H/NAD(P) ratio. Graded increases in autofluorescence were seen in response to graded decreases in PO2, suggesting that mitochondrial function is progressively altered below a PO2 of about 60 mmHg. 3. A mitochondrial origin for the NAD(P)H autofluorescence was suggested by the mutual exclusion of the responses to anoxia and cyanide. 4. Oxidized flavoproteins fluoresce when excited at 450 nm with an emission peak at 550 nm. The small signals obtained under these conditions increased with uncoupler and showed a graded decrease with falling PO2 reflecting a rise in the FADH/FAD ratio. 5. Hypoxia raises [Ca2+]i. The hypoxia-induced changes in mitochondrial function were not secondary to this rise. A brief K(+)-induced depolarization leads to a transient increase in [Ca2+]i. At the same time there is a rapid decrease in NAD(P)H autofluorescence followed by an increase that far outlasts the rise in [Ca2+]i. This delayed increase in autofluorescence was smaller than was the increase with anoxia, even though K(+)-induced depolarization raised [Ca2+]i more than does anoxia. In Ca(2+)-free solutions the depolarization-induced changes were abolished, while those associated with hypoxia were maintained. 6. The changes of autofluorescence with K(+)-induced depolarization appear to reflect (i) oxidation of NAD(P)H by stimulation of respiration following mitochondrial Ca2+ uptake and (ii) reduction of NAD(P) by the Ca(2+)-dependent activation of mitochondrial dehydrogenases. This activation could last several minutes following only 100 ms depolarization, while the changes accompanying hypoxia closely followed the time course of the change in PO2. 7. In similarly isolated rat or mouse chromaffin cells and mouse dorsal root ganglion neurons under identical conditions, no measurable change in autofluorescence or in [Ca2+]i was seen until the PO2 fell below about 5 mmHg. 8. Carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP) increases O2 consumption, oxidizing mitochondrial NADH and hence decreasing autofluorescence, (delta FFCCP). Blockade of electron transport by anoxia or CN- decreases O2 consumption, increasing mitochondrial NADH/NAD and autofluorescence (delta FCN). The fractional change in autofluorescence with FCCP, delta FFCCP/delta FFCCP+FCN), is thus a measure of resting O2 consumption.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432707 TI - All-or-nothing Ca2+ mobilization from the intracellular stores of single histamine-stimulated HeLa cells. AB - 1. Histamine-stimulated mobilization of intracellular Ca2+ stores was monitored in intact and permeabilized populations of HeLa cells using both the fluorescent Ca2+ indicator Fura-2 and 45Ca2+ measurements. Digital video imaging of Fura-2 loaded cells was used to measure the intracellular calcium concentration ([Ca2+]i) of single cells. 2. In populations of HeLa cells, histamine caused a concentration-dependent increase in cytoplasmic [Ca2+]. The initial transient increase was independent of extracellular Ca2+ (Ca2+o) and was followed by a sustained increase that was abolished by removal of Ca2+o. 3. In Ca(2+)-free medium ([Ca2+]o < 1 microM), a maximal histamine concentration (25 microM) caused a transient increase in [Ca2+]i, and a subsequent challenge with histamine failed to evoke a further response indicating that the inositol 1,4,5-trisphosphate (InsP3)-sensitive Ca2+ stores had been completely emptied. Lower concentrations of histamine (0.5-10 microM) caused smaller, concentration-dependent increases in [Ca2+]i that were also transient. After exposure to these low histamine concentrations, where [Ca2+]i returned to baseline within 2 min, addition of a higher histamine concentration evoked a further increase in [Ca2+]i. The second increase in [Ca2+]i was inversely proportional to the increase caused by the first exposure to histamine, indicating that Ca2+ released in the initial response was not substantially resequestered into histamine-sensitive stores. 4. Single HeLa cells challenged with low concentrations of histamine in Ca(2+)-free medium responded with transient increases in [Ca2+]i, but individual cells differed in their sensitivity with 51% of cells responding to 1 microM, and 98% responding to 25 microM-histamine. 5. When single cells in Ca(2+)-free medium were challenged with stepwise increases in histamine concentration, they responded to each step with a transient [Ca2+]i increase after which [Ca2+]i returned to baseline within 1 min. Prolonging the interval between histamine additions by up to 25 min did not affect the [Ca2+]i increase evoked by a subsequent histamine addition. 6. Unidirectional 45Ca2+ efflux from saponin permeabilized HeLa cells showed that, under conditions that prevented Ca2+ resequestration, submaximal concentrations of InsP3 rapidly emptied only a fraction of the InsP3-sensitive Ca2+ stores. The failure of low InsP3 concentrations to fully mobilize the InsP3-sensitive Ca2+ stores was not a consequence of InsP3 degradation. 7. We conclude that within single HeLa cells, intracellular Ca2+ stores are heterogeneous in their sensitivity to InsP3, and the fraction of Ca2+ stores mobilized by InsP3 increases as the InsP3 concentration increases. PMID- 1432708 TI - A caffeine- and ryanodine-sensitive Ca2+ store in bullfrog sympathetic neurones modulates effects of Ca2+ entry on [Ca2+]i. AB - 1. We studied how in changes in cytosolic free Ca2+ concentration ([Ca2+]i) produced by voltage-dependent Ca2+ entry are influenced by a caffeine-sensitive Ca2+ store in bullfrog sympathetic neurones. Ca2+ influx was elicited by K+ depolarization and the store was manipulated with either caffeine or ryanodine. 2. For a time after discharging the store with caffeine and switching to a caffeine-free medium: (a) [Ca2+]i was depressed by up to 40-50 nM below the resting level, (b) caffeine responsiveness was diminished, and (c) brief K+ applications elicited [Ca2+]i responses with slower onset and faster recovery than controls. These effects were more pronounced as the conditioning caffeine concentration was increased over the range 1-30 mM. 3. [Ca2+]i, caffeine and K+ responsiveness recovered in parallel with a half-time of approximately 2 min. Recovery required external Ca2+ and was speeded by increasing the availability of cytosolic Ca2+, suggesting that it reflected replenishment of the store at the expense of cytosolic Ca2+. 4. During recovery, Ca2+ entry stimulated by depolarization had the least effect on [Ca2+]i when the store was filling most rapidly. This suggests that the effect of Ca2+ entry on [Ca2+]i is modified, at least in part, because some of the Ca2+ which enters the cytosol during stimulation is taken up by the store as it refills. 5. Further experiments were carried out to investigate whether the store can also release Ca2+ in response to stimulated Ca2+ entry. In the continued presence of caffeine at a low concentration (1 mM), high K+ elicited a faster and larger [Ca2+]i response compared to controls; at higher concentrations of caffeine (10 and 30 mM) responses were depressed. 6. Ryanodine (1 microM) reduced the rate at which [Ca2+]i increased with Ca2+ entry, but not to the degree observed after discharging the store. At this concentration, ryanodine completely blocked responses to caffeine but had no detectable effect on Ca2+ channel current or the steady [Ca2+]i level achieved during depolarization. 7. We propose that, depending on its Ca2+ content, the caffeine-sensitive store can either attenuate or potentiate responses to depolarization. When depleted and in the process of refilling, the store reduces the impact of Ca2+ entry as some of the Ca2+ entering the cytosol during stimulation is captured by the store.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432709 TI - Calcium requirements for secretion in bovine chromaffin cells. AB - 1. Measurements of membrane capacitance and intracellular Ca2+ concentration, [Ca2+]i, were used to examine the Ca2+ dependence of secretion in single adrenal chromaffin cells. 2. Intracellular dialysis of Ca2+, through a patch pipette, promoted secretion; the rate of secretion increased monotonically as [Ca2+]i was elevated, while the total amount of secretion reached a maximum at 1.5 microM Ca2+ and declined at high [Ca2+]i. 3. Release of Ca2+ from internal stores, using bradykinin or ionomycin, transiently elevated [Ca2+]i and the rate of secretion. 4. Considering responses to both Ca2+ dialysis and release from internal stores, it appears that the rate of secretion increases over a range of [Ca2+]i levels above 0.2 microM and saturates at concentrations greater than 10 microM, if at all. Secretion appears to have a Hill coefficient for Ca2+ of about 2. At [Ca2+]i greater than 1-2 microM, prolonged elevation of [Ca2+]i, via dialysis, produced lower rates of secretion than transient elevation of [Ca2+]i caused by release from internal stores. This may have been caused by a depletion of readily releasable chromaffin granules during prolonged elevation of [Ca2+]i. 5. Brief depolarizing pulses produced transient rises in both [Ca2+]i and the rate of secretion. The ability of these pulses to evoke secretion 'washed out' during prolonged intracellular dialysis, due to both reduced Ca2+ influx and a diminished ability of the cell to secrete in response to a given Ca2+ load. 6. The kinetics of the secretory response depended upon the size of the depolarization-induced Ca2+ load; small rises in [Ca2+]i increased membrane capacitance only during the depolarization, while larger rises in [Ca2+]i produced increases both during and following the depolarization. The secretory responses that outlasted the depolarization appeared to be due to persistent elevation of [Ca2+]i. Secretory responses were sometimes followed by a slower decline in membrane capacitance, probably due to endocytosis of membrane. 7. Comparison of the rates of secretion measured during depolarization to those produced by Ca2+ dialysis or release from internal stores suggests that [Ca2+]i at secretory sites can exceed 10 microM during depolarization. The spatially averaged measurements of [Ca2+]i indicate much smaller levels of [Ca2+]i; thus, there must be pronounced spatial gradients of [Ca2+]i during depolarization. PMID- 1432710 TI - Synaptic interaction between medullary respiratory neurones during apneusis induced by NMDA-receptor blockade in cat. AB - 1. Termination of inspiration is an essential component of respiratory rhythm generation and its perturbation can result in apneusis, i.e. significant prolongation of mechanisms, we studied the postsynaptic events in respiratory neurones during apneustic respiratory periods, and compared them to normal respiratory cycles. 2. Experiments were performed in pentobarbitone anaesthetized, paralysed, thoracotomized cats ventilated with a constant volume or a cycle-triggered constant pressure pump. Apneusis, separated by normal cycles, was induced as follows: the animal was ventilated by a cycle-triggered pump that normally inflated the lungs during the inspiratory burst of phrenic nerve discharge. The NMDA-receptor blocker MK-801 [(+)-5-methyl-10,11-dihydro-5H dibenzo[a,d]cyclohepten-5, 10-iminemaleate] (0.3-0.7 mg/kg) was administered intravenously, and, for designated breaths, inflation of the lungs was withheld during neural inspiration. 3. Membrane potential trajectories of forty-one late expiratory (E-2) and eight postinspiratory (PI) neurones of the caudal ventral respiratory group were analysed before and/or after MK-801 administration, during normal and apneustic periods. 4. Before MK-801 administration, withholding lung inflation caused modest (10-20%) lengthening of the inspiratory period; after MK 801 administration, withholding inflation caused apneusis. Provided that the lungs were inflated during the inspiratory phase, the temporal pattern of phrenic nerve, recurrent laryngeal nerve and membrane potential trajectories of E-2 and PI neurones were not significantly altered by MK-801. Apneusis following NMDA receptor blockade produced consistent changes in the synaptic activation patterns of E-2 neurones. In particular, the slow late inspiratory-related depolarization pattern of E-2 neurones was consistently retarded during apneustic inspiratory phases when compared to normal inspiratory phases. This was due to continuation of Cl(-)-mediated synaptic inhibition of E-2 neurones. Superior laryngeal nerve stimulation stopped apneusis and sustained membrane hyperpolarization of E-2 neurones similar to lung inflation. 5. During the plateau phase of apneusis, correlated 10-20 Hz oscillations could be observed in the integrated phrenic and recurrent laryngeal nerve activities as well as in the membrane potential of E-2 neurones. 6. We conclude that: (i) the prolonged inhibition of E-2 neurones during apneusis is indicative of the process responsible for the prolongation of the inspiratory phase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432711 TI - Pulsatile release of acetylcholine by nerve terminals (synaptosomes) isolated from Torpedo electric organ. AB - 1. Electrophysiological detection of acetylcholine (ACh) release by synaptosomes from the electric organ of Torpedo was searched for by laying the isolated nerve terminals on a culture of Xenopus embryonic muscle cells (myocytes), and by recording the ACh-induced inward currents in the myocytes. 2. Whole-cell recording in one of the myocytes revealed rapid inward currents that where generated soon after synaptosome application. These pulsatile events strongly resembled those occurring normally during the early phase of synaptogenesis after nerve-muscle contact in Xenopus cell cultures. They were called spontaneous synaptic currents (SSCs). 3. The SSCs produced by the synaptosomes had a rapid time course, with mean time-to-peak and half-decay times of 2.6 +/- 0.4 ms and 6.0 +/- 1.1 ms, respectively. Most events had a falling phase that could be fitted with a single exponential. The mean time constant of decay was 6.2 +/- 1.1 ms. More than half of the SSCs (approximately 60%) constituted a rather homogenous population in which the time-to-peak versus amplitude showed a positive relationship, the smallest events displaying a shorter time course. The rest of the SSCs had a more variable and slower time course. Such events are also observed in young and mature junctions in situ. 4. The amplitudes of SSCs had a wide distribution which was skewed towards the smallest values. The mean amplitude was 65.2 +/- 16.1 pA. 5. During the minutes following an application of synaptosomes, the frequency of the SSCs tended to decrease, but their mean amplitude remained constant. Such behaviour could be reproduced during several successive additions of synaptosomes while recording in the same myocyte. 6. Just after synaptosome application, the SSCs were superposed to a noisy inward current that lasted for 20-60 s. Noise analysis of this current gave the values of 0.7 +/ 0.1 pA for the mean amplitude of the elementary event, and 4.7 +/- 0.2 ms for its mean duration, values that compare well with those reported for the activation of frog embryonic nicotinic receptor. This suggests that the noisy current was due to ACh molecules set free by synaptosomes which were either damaged or which released ACh at some distance. This view was strengthened by biochemical analysis of ACh release by synaptosomes in vitro. 7. Tubocurarine reversibly abolished the appearance of both the noise and the synaptosome generated SSCs, showing that these currents were due to the action of ACh.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432712 TI - Relative mitochondrial membrane potential and [Ca2+]i in type I cells isolated from the rabbit carotid body. AB - 1. In the accompanying paper (Duchen & Biscoe, 1992) we have described graded changes in autofluorescence derived from mitochondrial NAD(P)H in type I cells of the carotid body in response to changes of PO2 over a physiologically significant range. These observations suggest that mitochondrial function in these cells is unusually sensitive to oxygen and could play a role in oxygen sensing. We have now explored further the relationships between hypoxia, mitochondrial membrane potential (delta psi m) and [Ca2+]i. 2. The fluorescence of Rhodamine 123 (Rh 123) accumulated within mitochondria is quenched by delta psi m. Mitochondrial depolarization thus increases the fluorescence signal. Blockade of electron transport (CN-, anoxia, rotenone) and uncoupling agents (e.g. carbonyl cyanide p trifluoromethoxy-phenylhydrazone; FCCP) increased fluorescence by up to 80-120%, while fluorescence was reduced by blockade of the F0 proton channel of the mitochondrial ATP synthase complex (oligomycin). 3. delta psi m depolarized rapidly with anoxia, and was usually completely dissipated within 1-2 min. The depolarization of delta psi m with anoxia (or CN-) and repolarization on reoxygenation both followed a time course well characterized as the sum of two exponential processes. Oligomycin (0.2-2 micrograms/ml) hyperpolarized delta psi m and abolished the slower components of both the depolarization with anoxia and of the subsequent repolarization. These data (i) illustrate the role of the F1-F0 ATP synthetase in slowing the rate of dissipation of delta psi m on cessation of electron transport, (ii) confirm blockade of the ATP synthetase by oligomycin at these concentrations, and (iii) indicate significant accumulation of intramitochondrial ADP during 1-2 min of anoxia. 4. Depolarization of delta psi m was graded with graded changes in PO2 below about 60 mmHg. The stimulus-response curves thus constructed strongly resemble those for [Ca2+]i and NAD(P)H with PO2. The change in delta psi m closely followed changes in PO2 with time. 5. The rate of rise of [Ca2+]i in response to anoxia is strongly temperature sensitive. The rate of depolarization of delta psi m with anoxia similarly increased at least two- to fivefold on warming from 22 to 36 degrees C. The change with FCCP was not significantly altered by temperature. 6. These data show that the mitochondrial membrane potential changes over a physiological range of PO2 values in type I cells. This contrasts with the behaviour in dissociated chromaffin cells and sensory neurons, in which no change was measurable until the PO2 fell close to zero.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432713 TI - Alveolar epithelial permeability in baboons: histamine and capsaicin. AB - 1. We investigated if changes in alveolar epithelial permeability could be initiated by various doses of the irritant capsaicin through stimulation of pulmonary afferent nerves either directly, or indirectly through the release of an intermediate cell mediator, and whether mediation of permeability involved histamine H1 and/or H2 receptors. 2. Alveolar epithelial permeability was indicated by the clearance of peripherally deposited 99mTc-DTPA (technetium-99m diethylenetriamine pentaacetate) aerosol in baboons. Aerosol challenge experiments were performed twice with histamine (32 mg/ml), once each with capsaicin (10(-6), 10(-5), 10(-4) and 10(-3) M), and once each with histamine (32 mg/ml) preceded by H1 (terfenadine) and H2 (ranitidine) antagonists alone and combined. 3. Mean half-time for 99mTc-DTPA clearance was 66 +/- 4 min. After histamine, it decreased to 41 +/- 5 min (P < 0.05), and after capsaicin it was 70 +/- 5 min (combined doses). Pretreatment with the H1 and H2 antagonists, either separately or in combination, did not consistently inhibit increases in 99mTc DTPA permeability. 4. Capsaicin caused tachypnoea only at 10(-3) M (P < 0.05). Inhibition of histamine-induced tachypnoea required both antagonists (P < 0.05) suggesting the existence of a population of peripheral sensory neurons possessing H1 and H2 receptors. Changes in permeability were unrelated to the changes in respiratory frequency. Thus, neither the mechanisms that stimulate respiratory frequency, nor the respiratory frequency per se, were responsible for increased alveolar epithelial permeability. 5. Capsaicin did not change epithelial permeability at doses that cause capsaicin-sensitive C fibre stimulation as delineated by increases in respiratory frequency. Nor does C fibre stimulation, induced by mediators released from pulmonary cells activated by low doses of capsaicin, increase epithelial permeability. These data suggest that in the primate, histamine increases epithelial permeability to small solutes by a mechanism independent of the activation of capsaicin-sensitive C fibres and capsaicin-initiated release of cell mediators. 6. These findings do not support a role for C fibre activation in regulating epithelial permeability of small solutes. PMID- 1432714 TI - Regulation by second messengers of the slowly activating, voltage-dependent potassium current expressed in Xenopus oocytes. AB - 1. Voltage-clamp recordings of membrane current were made from Xenopus oocytes that had been injected with RNA which had been transcribed in vitro from a cloned complementary DNA. 2. Depolarization from -80 mV evoked outward potassium currents that developed very slowly. At -20 mV the time constant for activation was about 50 s, and at +40 mV about 6 s. 3. The potassium current was increased by the calcium ionophore A23187 or by intracellular injection of inositol 1,4,5 trisphosphate (IP3), each of which should increase the intracellular calcium concentration ([Ca2+]i). The current was decreased by injection of BAPTA (1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). The current was also reduced by phorbol esters; this effect was blocked by staurosporine. 4. In oocytes that had also been injected with RNA encoding the 5-hydroxytryptamine (5 HT2) receptor, 5-HT increased the potassium current. After caffeine pretreatment, to block the release of intracellular calcium, 5-HT decreased the current; this decrease was prevented by staurosporine. 5. It is concluded that the slowly activating, voltage-dependent potassium current expressed in Xenopus oocytes is increased by increases in [Ca2+]i and is decreased by activation of protein kinase C. Stimulation of 5-HT2 receptors can have both these effects, but the former normally predominates. PMID- 1432715 TI - Co-ordination of pumping in isolated bovine lymphatic vessels. AB - 1. Segments of bovine mesenteric lymphatic of varying diameter taken from different parts of the lymphatic tree were cut to 20 mm in length and set up so that measurements could be made of spontaneous isometric contractions. 2. There was considerable variability in frequency of spontaneous contractions but this was independent of resting tension. There was no significant correlation between lymphatic diameter and inherent frequency of contraction. 3. Isolated segments of bovine mesenteric lymphatic 70-80 mm in length were cannulated and set up in a three-compartment organ bath which allowed independent temperature control in each compartment. Pressure was recorded at inflow and outflow ends and experiments were video recorded. 4. Contractile activity was normally initiated at the end of the lymphatic maintained at the higher temperature and the contractile wave was propagated along the length of the vessel. 5. Propagation could occur either in the direction of valve orientation (orthograde) or retrogradely. The volume of fluid pumped was not significantly affected by the direction of propagation. 6. Perfusion of the central compartment with Krebs solution at 0-2 degrees C disrupted normal propagation and allowed the two parts of the lymphatic to contract at different frequencies although the two parts maintained an approximately 2:1 ratio. 7. Perfusion of the central compartment with 10 mM-heptanol also disrupted normal propagation but the rates on either side of the partition bore no harmonic relationship to one another. 8. These results suggest that relatively short segments of lymph duct have the ability to contract spontaneously and that their inherent frequencies are not determined by their position in the lymphatic tree. The results are consistent with the existence of electrical coupling along the lymphatic's length and they suggest that over distances of at least 80 mm independent pacemakers are capable of mutual entrainment at a frequency representing a compromise between the fastest and slowest components. PMID- 1432716 TI - Basal Ca2+ and the oscillation of Ca2+ in caffeine-treated bullfrog sympathetic neurones. AB - 1. Effects of caffeine on the intracellular free Ca2+ concentration ([Ca2+]i) in single bullfrog sympathetic neurones in excised tissue were studied by recording Fura-2 fluorescence excited at 340, 361 or 380 nm and taking their ratios (R340/380 or R361/380). 2. Caffeine (3-10 mM) produced oscillation of [Ca2+]i and an 'apparent' decrease in the basal level of [Ca2+]i during a period between phasic rises. The mechanism of the latter effect was analysed in relation to the mechanism of the former. 3. Caffeine (3-10 mM) increased Fura-2 fluorescence in a range of excitation wavelength from 330 to 390 nm. The ratios of fluorescences, R340/380 and R361/380, however, were not significantly affected by caffeine. These results suggest that the 'apparent' reduction in the basal [Ca2+]i seen as a decrease in R340/380 or R361/380 results from a true decrease in [Ca2+]i. 4. Caffeine-induced decrease in [Ca2+]i persisted for every period between phasic rises of [Ca2+]i during [Ca2+]i oscillation, and after the blockade of [Ca2+]i oscillation by ryanodine. The decrease in the latter condition lasted for more than 20 min. 5. The decrease in the basal [Ca2+]i depended on the external Ca2+ concentration and was not mimicked by the action of cyclic nucleotides. 6. Possible mechanisms underlying the decrease in the basal [Ca2+]i produced by caffeine (effects on Ca2+ transport at the cell or Ca(2+)-storing organelle membrane) and their significance in relation to the [Ca2+]i oscillation were discussed. PMID- 1432717 TI - Independent control of human finger-tip forces at individual digits during precision lifting. AB - 1. Subjects lifted an object with two parallel vertical grip surfaces and a low centre of gravity using the precision grip between the tips of the thumb and index finger. The friction between the object and the digits was varied independently at each digit by changing the contact surfaces between lifts. 2. With equal frictional conditions at the two grip surfaces, the finger-tip forces were about equal at the two digits, i.e. similar vertical lifting forces and grip forces were used. With different frictions, the digit touching the most slippery surface exerted less vertical lifting force than the digit in contact with the rougher surface. Thus, the safety margins against slips were similar at the two digits whether they made contact with surfaces of similar or different friction. 3. During digital nerve block, large and variable safety margins were employed, i.e. the finger-tip forces did not reflect the surface conditions. Slips occurred more frequently than under normal conditions (14% of all trials with nerve block, <5% during normal conditions), and they only occasionally elicited compensatory adjustments of the finger-tip forces and then at prolonged latencies. 4. The partitioning of the vertical lifting force between the digits was thus dependent on digital afferent inputs and resulted from active automatic regulation and not just from the mechanics of the task. 5. The safety margin employed at a particular digit was mainly determined by the frictional conditions encountered by the digit, and to a lesser degree by the surface condition at the same digit in the previous lift (anticipatory control), but was barely influenced by the surface condition at the other digit. 6. It was concluded that the finger-tip forces were independently controlled for each digit according to a 'non-slip strategy'. The findings suggest that the force distribution among the digits represents a digit-specific lower-level neural control establishing a stable grasp. This control relies on digit-specific afferent inputs and somatosensory memory information. It is apparently subordinated to a higher-level control that is related to the total vertical lifting and normal forces required by the lifting task and the relevant physical properties of the manipulated object. PMID- 1432718 TI - A study of glycogen depletion and the fibre-type composition of cat skeleto fusimotor units. AB - 1. We have used the glycogen-depletion technique, combined with myofibrillar ATPase (mATPase) staining for muscle fibre type, to study the fibre-type composition of four skeleto-fusimotor (beta) units in cat peroneus tertius, namely, one beta dynamic (beta d) unit and three beta static (beta s) units. 2. Depletion of glycogen was observed in serial cross-sections of thirty-four beta unit extrafusal muscle fibres of various types traced from origin to insertion. No fibre was depleted of glycogen throughout its length; depletion was restricted to a number of zones, usually about five. Oxidative (type I) and oxidative glycolytic (type IIA) fibres were depleted for a significantly greater proportion of their total length than glycolytic IIB fibres. 3. The fibre-type composition of the beta d unit was determined by tracing its fibres from end to end. The muscle unit consisted of one intrafusal bag1 fibre and ninety-three extrafusal muscle fibres comprising seventy-six type I fibres, eleven IIC fibres, and six fibres that changed from IIC to I during the course of their length (IIC/I fibres). The extrafusal fibre-type composition was thus 81.7% I plus 18.3% IIC and IIC/I. 4. The three beta s units (beta s1, beta s2, beta s3) were all fast contracting and fatigued rapidly. Identification of their extrafusal fibre types, made in 1 mm2 areas sampled from different parts of each unit, gave mixed compositions as follows: beta s1, IIB + 6.7% IIA; beta s2, IIB + 5.8% IIA; beta s3, IIB + 29.9% IIA. The intrafusal component of each unit included either one or two long chain fibres. 5. In a discussion of the results, the fact that the continuous stimulation of extrafusal muscle fibres does not deplete them of glycogen throughout their length is examined in relation to the work of others who have assumed that it did. With regard to the finding of mixed extrafusal fibre types in the beta units, a distinction is drawn between minimal (around 5%) and moderate mixing. It is suggested that minimal mixing may occur in any motor unit as the outcome of endplate degeneration with foreign replacement, but that moderate mixing indicates an on-going process of conversion from one fibre type to another which in the adult may prove to occur only among beta units. PMID- 1432719 TI - Single C nociceptor responses and psychophysical parameters of evoked pain: effect of rate of rise of heat stimuli in humans. AB - 1. Effects of rate of rise of temperature stimuli applied to skin on (i) unitary receptor threshold and frequency response often single C nociceptors, and (ii) on magnitude and reaction times of evoked pain were studied in fifteen healthy human volunteers. 2. Temperature ramps of 32 to 45 or 47 degrees C were applied at three consistent rates of rise to receptive fields of C nociceptors in dorsum of foot (n = 9) or hand (n = 1). For rates of rise of 0.3, 2.0 and 6.0 degrees C/s, mean receptor threshold for heat was remarkably uniform: 41.5 +/- 0.57, 41.5 +/- 0.61 and 41.9 +/- 0.71 degrees C respectively. 3. The mean discharge rate of the ten cutaneous C nociceptors increased with rate of rise of temperature stimuli: 1.22 +/- 0.13, 4.57 +/- 0.49 and 13.45 +/- 0.71 impulses/s, respectively, for stimulus temperature rates of 0.3, 2.0 and 6.0 degrees C/s. 4. Magnitude estimates of pain for thirteen subjects also increased with rate of rise of temperature stimuli. Mean normalized magnitude estimates of heat pain were: 11.8 +/- 1.55, 15.1 +/- 0.84 and 28.0 +/- 1.87 for stimulus rates of rise of 0.3, 2.0 and 6.0 degrees C/s, respectively. 5. Results of simultaneous recordings of reaction time for pain and of C nociceptor responses to heat ramps given at 2.0 degrees C/s, in three subjects, indicate that under those circumstances heat pain messages are exclusively mediated by C nociceptors. PMID- 1432720 TI - The minimal inhibitory synaptic currents evoked in neonatal rat motoneurones. AB - 1. Tight-seal whole-cell recordings were made from lumbar motoneurones visually identified in thin slices of neonatal rat spinal cord. The inhibitory postsynaptic currents (IPSCs) were evoked by extracellular stimulation of a neighbouring internuncial neurone in the presence of glutamate receptor antagonists. 2. Glycinergic IPSCs were recorded in the presence of bicuculline. The IPSCs appeared in an all-or-none manner as the graded stimulus intensity exceeded a certain threshold. Their latencies showed a unimodal distribution with a mean of 0.81 ms at 37 degrees C. Thus, the observed IPSCs are suggested to be monosynaptically evoked unitary IPSCs. The mean conductance of unitary IPSCs was 2.9 +/- 1.2 nS (+/- S.D.). 3. When the external Ca2+ concentration ([Ca2+]o) was reduced, the number of failures in response to stimulation increased, thereby reducing the mean amplitude of IPSCs. The mean amplitude of IPSCs was linearly related to the [Ca2+]o (0.35-1.4 mM) with a mean slope of 3.1 +/- 0.67 on double logarithmic co-ordinates. 4. The amplitude of individual IPSCs decreased with decrease in [Ca2+]o. However, below 0.7 mM [Ca2+]o, the mean amplitude of IPSCs (excluding failures) reached a steady minimum level. The mean conductance of these IPSCs measured in 0.5 mM [Ca2+]o was 657 +/- 281 pS. 5. The minimal IPSCs had a coefficient of variation of 0.50 +/- 0.13. No clear correlation was observed between the rise time and the amplitude of minimal IPSCs evoked in individual motoneurones, indicating that the amplitude variability is not due to the different synaptic locations. 6. Spontaneous miniature IPSCs were recorded from motoneurones in the presence of tetrodotoxin. The miniature IPSCs had a mean conductance of 739 +/- 278 pS, being comparable to the minimal evoked IPSCs. 7. Under various internal and external Cl- concentration, the reversal potential of the IPSCs (EIPSC) approximately coincided with the Cl- equilibrium potential. A 730-fold change in the potassium concentration gradient across the membrane did not affect the EIPSC. The permeability ratio of K+ to Cl- (Pk/PCl) was less than 0.05. 8. It is concluded that the IPSCs are carried almost exclusively by Cl- and that the minimal evoked IPSCs represent the quantal response of the transmitter. PMID- 1432721 TI - Serotonin regulates the phase of the rat suprachiasmatic circadian pacemaker in vitro only during the subjective day. AB - 1. The suprachiasmatic nucleus (SCN) of the hypothalamus is the primary pacemaker for circadian rhythms in mammals. The 24 h pacemaker is endogenous to the SCN and persists for multiple cycles in the suprachiasmatic brain slice. 2. While serotonin is not endogenous to the SCN, a major midbrain hypothalamic afferent pathway is serotonergic. Within this tract the dorsal raphe nucleus sends direct projections to the ventrolateral portions of the SCN. We investigated a possible regulatory role for serotonin in the mammalian circadian system by examining its effect, when applied at projection sites, on the circadian rhythm of neuronal activity in rat SCN in vitro. 3. Eight-week-old male rats from our inbred colony, housed on a 12 h light: 12 h dark schedule, were used. Hypothalamic brain slices containing the paired SCN were prepared in the day and maintained in glucose and bicarbonate-supplemented balanced salt solution for up to 53 h. 4. A 10(-11) ml drop of 10(-6) M-serotonin (5-hydroxytryptamine (5-HT) creatinine sulphate complex) in medium was applied to the ventrolateral portion of one of the SCN for 5 min on the first day in vitro. The effect of the treatment at each of seven time points across the circadian cycle was examined. The rhythm of spontaneous neuronal activity was recorded extracellularly on the second and third days in vitro. Phase shifts were determined by comparing the time-of-peak of neuronal activity in serotonin- vs. media-treated slices. 5. Application of serotonin during the subjective day induced significant advances in the phase of the electrical activity rhythm (n = 11). The most sensitive time of treatment was CT 7 (circadian time 7 is 7 h after 'lights on' in the animal colony), when a 7.0 +/ 0.1 h phase advance was observed (n = 3). This phase advance was perpetuated on day 3 in vitro without decrement. Serotonin treatment during the subjective night had no effect on the timing of the electrical activity rhythm (n = 9). 6. The specificity of the serotonin-induced phase change was assessed by treating slices in the same manner with a microdrop of serotonergic agonists, 5 carboxamidotryptamine, that targets the 5-HT1 class of receptors, or 8-hydroxy dipropylaminotetralin (8-OH DPAT), that acts on the 5-HT1A receptor subtype.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432723 TI - Interface shear stresses during ambulation with a below-knee prosthetic limb. AB - Shear stresses on a residual limb in a prosthetic socket are considered clinically to contribute to tissue breakdown in below-knee amputees. When applied simultaneously with normal stresses, they can cause injury within the skin or can generate an abrasion on the surface. To gain insight into shear stresses and parameters that affect them, interface stresses were recorded on below-knee amputee subjects during walking trials. On the tibial flares, resultant shear ranged from 5.6 kPa to 39.0 kPa, while on the posterior surface it ranged from 5.0 kPa to 40.7 kPa. During stance phase, anterior resultant shears on a socket were directed toward the apex while posterior resultant shears were directed downward approximately perpendicular to the ground. Waveform shapes were usually double-peaked, with the first peak at 25% to 40% into stance phase and the second peak at 65% to 85% into stance. Application of these results to residual limb tissue mechanics and prosthetic design is discussed. PMID- 1432722 TI - Transient chloride binding as a contributory factor to corneal stromal swelling in the ox. AB - 1. Investigations were made of the cation exchange capacity of fresh isolated ox corneal stroma (Q, units: mequiv fixed stromal charge/kg stromal fluid) at pH 7.4 over a variety of stomal hydrations (H, units: kg stromal fluid/kg dry tissue) both above and below the physiological hydration of 3.2, whilst the stromas were immersed in a variety of sodium chloride solutions (range 5-1000 mM). 2. At any particular salt concentration, the product QH (dry tissue exchange capacity, units: mequiv/kg dry tissue) appeared constant, over all the hydrations investigated. 3. Dry tissue exchange capacity (QH) varied, however, when the bathing salt concentration was altered. It varied between 55 mequiv/kg dry tissue (e.g. Q = 17 mequiv at H = 3.2) in 5 mM-NaCl to 240 mequiv/kg dry tissue (e.g. Q = 75 mequiv/l at H = 3.2) in 1000 mM-NaCl. 4. The variation of stromal exchange capacity in NaCl solutions of different concentrations was similar when detected by three independent procedures: stromal gel pressure measurements, intrastromal sodium ion distributions, and intrastromal electrical potentials. 5. Intrastromal chloride ion distributions were anomalous. Total chloride (measured by radio isotopes) was consistently higher than that predicted by Donnan theory. 6. The data were consistent with Elliott's hypothesis that a fraction of intrastromal chloride ions bind to the corneal stromal matrix and in so doing contribute to the fixed negative charge of the stroma. 7. Our observations may be explained by a model of the cation exchange capacity of ox cornea which has two types of components. On is (at constant pH) invariant, and has a dry tissue exchange capacity of about 50 mequiv/kg dry tissue, and is probably generated by the sulphonic and carboxylic acid groups of the glycosaminoglycans. The other is explained by supposing it to consist of a chloride binding ligand which exhibits first order binding, is half occupied at ambient chloride concentrations of 300 mM, and has a total capacity of 240 mequiv/kg dry tissue. 8. Partial stromal extraction with 4 M-guanidine HCl indicated that the chloride binding ligand is not associated with the collagen molecules in the corneal stromal fibrils. 9. It is suggested that such a stromal chloride ion binding ligand would help to stabilize the hydration and transparency of the living cornea when it is exposed to environments of varying tonicity (such as in river or sea bathing). PMID- 1432724 TI - Comparative effects of posture on pressure and shear at the body-seat interface. AB - This study considers the effects of seated posture and body orientation on the pressure-distribution and surface shear (tangential) forces acting at the body seat interface. Nine postures typically assumed by wheel-chair users were studied. Comparisons were made within and between two study groups, made up of 12 subjects with spinal cord injuries (SCI) and 10 nondisabled subjects. Both interface pressure and the surface shear were measured simultaneously in each of nine reproducible, seated postures. The same seat cushion was used for all trials. The Oxford Pressure Monitor, a pneumatic cell device, was used to measure and record the interface pressures. Instrumentation for measuring and recording the surface shear force was constructed specifically for the study. Analysis consisted of statistically comparing changes in pressure values and shear forces derived from eight sitting postures with reference to values recorded in a defined neutral sitting posture. The pressure-distribution findings suggest that in the postures studied SCI subjects have maximum pressures that are higher than nondisabled subjects in all postures, ranging from 6% to 46% depending on the posture. Maximum pressures can be reduced by postural changes: forward flexion to 50 degrees, -9%; backrest recline to 120 degrees, -12%; and, full body tilt, 11%. On average, the SCI group members have peak pressure gradients (PPG) that are 1.5 to 2.5 greater than the nondisabled group. The maximum reduction in PPG occurred at backrest recline of 120 degrees, -18%. Tangential shear force acts at the body-seat interface in all nine postures studied. Extrapolation of results suggests that full-body tilt to approximately 25 degrees reduces the surface shear force to near zero. In contrast, a backrest-only recline of 20 degrees causes a 25% increase in the surface shear force. These results suggest that caution must be taken when using nondisabled subjects as surrogates for people with SCI because of the inherent differences between the groups. Also, researchers and clinicians should recognize that posture and body orientation in space are additional variables that can have a profound effect on the interaction between a seated person and his or her supporting surface. PMID- 1432725 TI - A manufacturing system for contoured foam cushions. AB - The design, application and evaluation of a specialized, personal computer-based manufacturing system for contouring foam cushions is presented. The topics discussed include both the hardware configuration and the software design. The target applications of this device are local or centralized fabrication of custom contoured seat cushions. Although the technologies used for the development and implementation of this system are not new, using a personal-computer-based (PC) controller in place of a stand-alone numerically controlled (NC) motion controller significantly reduced the cost associated with this component. Further reductions in cost resulted from an optimization of the mechanical configuration for the dedicated task of carving foam cushions. PMID- 1432726 TI - Application of a programmable dual-channel adaptive electrical stimulation system for the control and analysis of gait. AB - A dual-channel electrical stimulation system with a stimulator and a programmer/stride analyzer was designed for clinical rehabilitation of gait and for subsequent daily use as an orthotic aid. The stimulator, with controls to adjust amplitude only (50 mA), adapts chosen stimulation sequences to the walking rate of a patient. Pulse duration (50-500 microseconds), frequency (5-120 Hz), shape (symmetrical biphasic, monophasic), stimulation sequences (16 stride segments) and their cycle (2-12 sec), and right/left foot-switch choices are selected for each patient and programmed into a separate unit. The programming unit also statistically processes the foot-switch data collected by the stimulator. The device was evaluated with regard to the programmable parameters, effectiveness during gait, and feasibility in clinical use. It was applied to 11 stroke patients and 10 brain injury patients during gait, stimulating 22 combinations of peroneal nerve and hamstring, quadriceps, triceps brachii, and gluteus maximus muscles. Forces on both feet, equinovarus, knee extension and hyperextension, elbow flexion, and hip extension were corrected. Selection of the stimulation sequences, their adaptation, range of pulse duration, and valid statistics were verified. Improved forces and joint angles were recorded together with significant changes in the stride time, length, and velocity by the stimulation. PMID- 1432727 TI - An examination of direct selection typing rate and accuracy for persons with high level spinal cord injury using QWERTY and default on-screen keyboards. AB - A single-subject rapid alternating treatment design with replication was used to compare the efficiency of two keyboard layouts, QWERTY and default, for persons with high-level spinal cord injury. The LIAISON system and proportional-drive chin controller provided computer access/writing to four subjects. Three efficiency characteristics were examined: keystrokes per minute, keystroke accuracy, and keystroke corrections. Baseline sessions were followed by 10 to 12 alternating treatment sessions for all subjects. Each alternating treatment session involved six text entry trials--three text entry trials using the QWERTY keyboard layout and three using the default keyboard layout. Four follow-up sessions were completed for each subject using the default keyboard configuration. Data analysis revealed that the default keyboard layout provided greater keystrokes per minute for two of the subjects. The keystroke accuracy was between 98% and 100% for all subjects on both keyboard layouts. The findings of this investigation revealed no clinically significant difference in typing performance across the two keyboard layouts for the participating subjects. The results also indicate that previous experience with a keyboard configuration is an important factor in determining performance. A possible treatment interaction or carryover effect between the two keyboard configurations was noted and has implications for the type of single-subject design used in future investigations. PMID- 1432728 TI - A human factors approach to adapted access device prescription and customization. AB - Adapted access device prescription and customization is often a lengthy and cumbersome process. To date, few objective procedures are available to assist in the prescription process. Rather, clinician and client rely on a trial-and-error approach that is often severely constrained by the size of their adaptive device collection as well as the extent of clinical expertise. Furthermore, the large number of available options and lack of information delineating the mechanical and physical characteristics of these devices means that therapists must take time away from direct clinical contact to probe each adaptation in detail. There is available in the human factors domain a body of literature that is highly relevant to adapted access. Of particular interest are the studies that have addressed issues related to the suitability of standard and alternative input devices in terms of task productivity (via improvements in input speed, accuracy, and endurance), and their ability to minimize the risk of acute and chronic work related dysfunction. This paper aims to consider the relevance of human factors research for physically disabled individuals. Three human factors issues--digit travel, digit loading, and device positioning--have been selected as representative of factors important in the configuration of adapted access devices. PMID- 1432729 TI - Automated fabrication of mobility aids (AFMA): below-knee CASD/CAM testing and evaluation program results. AB - In 1988 the Department of Veterans Affairs Rehabilitation Research and Development Service, under the directorship of Margaret J. Giannini, M.D., began a nationally directed computer-aided design and computer-aided manufacturing (CAD/CAM) research program for the Automated Fabrication of Mobility Aids (AFMA). Under this program CAD/CAM research and development centers were established at the Prosthetics Research Study in Seattle, WA; at Northwestern University and the VA Lakeside Medical Center in Chicago, IL; and at the VA Medical Center and New York University Medical Center in New York, NY. These three centers conducted a collaborative program: (a) to introduce CAD/CAM technologies to prosthetists, physicians, therapists, and rehabilitation health care professionals in the United States; (b) to evaluate the feasibility of using CAD/CAM systems in clinical prosthetics settings; (c) to test and evaluate the University College London-Bioengineering Center's and the University of British Columbia-Medical Engineering Resource Unit's respective systems for the computer-aided design and computer-aided manufacture of prosthetic sockets (CASD/CAM) for below-knee amputees; and, (d) to obtain quantitative data for refinement of the CASD/CAM systems tested, and for the development of new, enhanced, more efficacious, and expedient systems. PMID- 1432730 TI - Comparison of signal-to-noise ratio of myoelectric filters for prosthesis control. AB - A comparison of signal-to-noise ratios and rise times was performed on several myoelectric filters used for muscle-force estimation and prosthesis control. Linear, averaging, and adaptive filters were compared using single as well as multiple electrode pairs (spatial filtering). The filters were matched for having the same rise time (0-95%) and the signal-to-noise ratios were measured off-line using the same myoelectric signal recording. The linear filter was a low-pass filter with a time constant of 80 ms. The averaging filter had an averaging time of 250 ms. The adaptive filter was the same as is used in the Utah Artificial Arm. The adaptive filter varied its time constant according to the rate of change of the signal mean. If the rate was high, the time constant was set low. If the rate was low, the time constant was set high. Spatial filtering is where the myoelectric signals from four cutaneous sites over the same muscle were summed, that is, spatially filtered, and the resultant signal was smoothed by the linear, averaging, or adaptive filter. Significant improvement in the signal-to-noise ratio has been shown over conventional linear or averaging filters when using spatial and adaptive filtering, both when used separately and when used together. PMID- 1432731 TI - Cementoblastoma and osteoblastoma: a comparison of histologic features. AB - Three cases of cementoblastoma (CB) and three cases of osteoblastoma (OB) were histologically compared. The aim of the study was to investigate whether CB and OB are different in other aspects than being connected with a tooth. CB cases were the following: maxillary lesions in a 23-year-old woman and a 22-yr-old man and a mandibular lesion in a 28-yr-old man. In one case the tumor was fused to the roots of two teeth. Of the OB cases, one occurred in the mandible of a 27-yr old man, one in the ankle of a 19-yr-old male and one in the thoracic vertebrae of a 27-yr-old man. Histologically, CB and OB had the same appearance including peripheral spiculae rimmed by swollen blasts. This histologic similarity between OB and CB indicates that the diagnosis CB should not be made unless the lesion is connected with a tooth. PMID- 1432732 TI - Enamel ultrastructure in pigmented hypomaturation amelogenesis imperfecta. AB - Hypomaturation amelogenesis imperfecta (AI) is a hereditary condition of enamel that is presumed to result from defects during the maturation stage of enamel development. This study characterized the enamel ultrastructure and enamel crystallite morphology, as well as the distribution of organic material in enamel affected with pigmented hypomaturation AI. Enamel exhibiting autosomal recessive pigmented hypomaturation AI was sectioned or fractured and examined using light microscopy, scanning electron microscopy and transmission electron microscopy. Enamel samples were treated with 30% NaOCl or 8 M urea to remove organic components and determine the effect of deproteinization on crystallite morphology. These were compared with untreated normal enamel samples. The enamel crystallites in hypomaturation AI exhibited considerable variability in size and morphology. Examination of deproteinized tissue indicated that the AI crystallites had a thick coating, presumably of organic or partially mineralized material, which was not visible in normal enamel. The results of this investigation provide further evidence that hypomaturation AI is associated with the retention of organic material that is most probably enamel protein. Enamel protein retention is likely to be involved in the inhibition of normal crystallite growth resulting in the morphological crystallite abnormalities associated with this disorder. PMID- 1432733 TI - Growth hormone regulates nucleolar organizer regions during odontogenesis in the rat. AB - Nucleolar organizers are major sites of ribosomal RNA synthesis and provide an index of transcriptional activity. In order to further define growth hormone actions on nucleolar organizer regions in tooth forming cells, hypophysectomized rats treated with growth hormone for 4 and 24 h, hypophysectomized and sham operated animals were used. After demineralization and standard paraffin embedding, longitudinal sections of maxillary incisors were stained by a silver stain technique to reveal nucleolar organizer regions. The area of these regions per nucleus was measured using a modified microdensitometer. Analyses of variance of the resulting data showed that preameloblasts and preodontoblasts have greater silver stained nucleolar organizer region values than ameloblasts and odontoblasts. Hypophysectomy reduced and growth hormone partly restored the level of nucleolar organizer regions in preameloblasts and preodontoblasts, but not in mature ameloblasts or odontoblasts. In the case of the younger preameloblasts and preodontoblasts, the effect of growth hormone was seen within 4 h of growth hormone injection. In conclusion, rRNA synthesis, as revealed by the specific silver staining of nucleolar organizer regions in tooth forming cells, appears to be regulated by growth hormone over a relatively short time frame. PMID- 1432735 TI - Expression of p53 mutant nuclear phosphoprotein in oral carcinoma and potentially malignant oral lesions. AB - An immunohistochemical study of primary oral squamous cell carcinomas (n = 37) with a monoclonal antibody (PAb 1801) specific to p53 antioncogene product demonstrated nuclear overexpression of the mutant protein in 35% of cases. Those positive included carcinomas without deep invasion suggesting that p53 mutation may occur in the early stages of progression of a malignancy. This is supported by the observation that mutant protein was detectable in limited amounts in 2 cases of oral mucosal dysplasia (n = 12). None of the normal or reactive oral mucosal tissues (n = 17) were positive for p53. The presence or absence of p53 was not correlated with the site of the lesion or its degree of differentiation. Our data suggest that p53 gene mutations are commonly involved in oral cancer but are neither sufficient nor necessary for the development of malignancy. Nevertheless, as this mutation is the commonest genetic change described so far in cancers in white caucasoids, it is possible that its presence can be used as a marker of risk in a high proportion of malignant and potentially malignant oral lesions. PMID- 1432736 TI - Major recurrent oral ulcers in AIDS: report of three cases. AB - We report the cases of three AIDS patients who developed major recurrent oral ulcers with severe odynophagia and weight loss. The patients were treated successfully with systemic steroids. Within the first week of prednisone therapy (40 mg/day), the symptoms improved and the lesions entirely healed. We suggest, on the bases of recent literature, that superantigens and the cytokine network could be involved and they should be considered in the immunopathogenic mechanisms of this type of ulcers. PMID- 1432734 TI - Odontogenic myxoma: histochemical and ultrastructural study. AB - Three cases of odontogenic myxoma are presented, two of which were located in the mandible and one in the maxilla. All cases demonstrated similar morphology by light microscopy. Immunohistochemical studies demonstrated positive reaction with antibodies to vimentin and actin, and negative reaction to antibody to S-100 protein. A 127-day-old human tooth bud was used as a control. The ultrastructural features performed on Case 3, when combined with the immunohistochemical findings suggest that the cells comprising odontogenic myxoma are of myofibroblastic origin. PMID- 1432737 TI - Ehlers Danlos syndrome type I with novel dental features. AB - The clinical, radiographic and histologic findings are described in two cases of Ehlers Danlos Syndrome Type I with novel dental features. Defective dentinogenesis principally affecting the mandibular incisors result in aplasia or hypoplasia of root development predisposing to localized periodontal disease. A striking radiographic appearance with a bulbous enlargement of the roots together with pulp stones is seen in other teeth. 'Giant channels' and vascular inclusions resembling 'intermediate cementum' are prominent within this area. No evidence of Type III procollagen or collagen was detected with indirect immunofluorescence. It is suggested that an inherited collagen abnormality in a component common to dentin, skin, ligament and tendon probably explains both EDS I and the dentin dysplasia. PMID- 1432738 TI - Infantile osteopetrosis: a case report on dental findings. AB - In this paper we have described the case of a 7-yr-old Moroccan osteopetrotic boy, who had received a bone marrow transplant (BMT). He was transplanted from his older brother and, despite immunosuppressive therapy, developed chronic graft versus-host disease and was placed on corticotherapy. Seven months after the bone marrow transplant, graft versus host disease (GVHD) was stabilized, but corticotherapy had inhibited growth. There was evidence of normalizing bone, his hearing was better but he had not recovered vision. Dental findings before the bone marrow transplant revealed some missing teeth, failure of teeth to erupt and decayed teeth but no enamel hypoplasia. The patient had developed one carious lesion on one unerupted tooth: bacteria seem to have found a way through the gubernaculum dentale. The scanning electronmicrographs showed decayed tooth and tissues fitted into each other. Since the bone marrow transplant, no tooth has erupted. We think that, in this case, failure of tooth eruption would be the sign of osteopetrosis. PMID- 1432739 TI - Hypophosphatasia: a family study involving a case diagnosed from gingival crevicular fluid. AB - Hypophosphatasia is an inherited disorder characterized by defective mineralization of the skeletal and dental structures of the body and deficient liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. There has been a tremendous advance in our knowledge of this condition over the last decade due to the advent of highly specific DNA probes and novel microanalytic techniques. The purpose of this paper is threefold: to review the dental aspects of current literature about this rare condition; to present a case (and family study) that was diagnosed in a 5-yr-old boy from 0.14 microliters of gingival crevicular fluid, using a new ultrasensitive chemiluminescent assay for the enzyme alkaline phosphatase; and to provide strong evidence for an autosomal dominant mode of inheritance. PMID- 1432740 TI - Student voice. PMID- 1432742 TI - Developing a nursing care plan for the depressed elderly patient. PMID- 1432741 TI - Practical nursing: a proud history; a promising future. PMID- 1432744 TI - Helping the patient and their family understand depression. PMID- 1432743 TI - Therapeutic advances in ulcerative colitis. AB - Ulcerative colitis is an inflammatory condition that requires individualized and innovative therapy for each patient depending on the symptoms, location, severity, and chronicity of the disease. It is most often a chronic illness that requires modification in treatment as the stage of the disease changes. Systemic and rectal aminosalicylates (sulfasalazine, mesalamine, olsalazine and corticosteroids) remain the most useful therapeutic agents. Rectally administered mesalamine and the forms of oral mesalamine appear to have significant advantage over sulfasalazine dosage forms. Future clinical usage and scientific study will determine the place of these newer agents among other medical therapies and the surgical management of ulcerative colitis. PMID- 1432745 TI - New clinical trial for prevention of yeast infections in HIV infected women. PMID- 1432746 TI - Legal briefs. PMID- 1432747 TI - LPN, business woman speaks at convention luncheon. PMID- 1432748 TI - Alzheimer's disease and other dementias. PMID- 1432749 TI - A personal journey through the abyss of depression. PMID- 1432750 TI - An unpredictable result from a torus palatinus removal and its treatment: a clinical report. PMID- 1432751 TI - Implant rehabilitation in Erdheim-Chester disease: a clinical report. AB - Successful osseointegration of endosseous titanium implants is thought to be dependent upon close apposition of bone to the implant surface. The integration of implants in this patient was achieved despite the lipid-laden histiocytic infiltration of the bone marrow. Presumably, enough unaffected stromal cells were present to allow sufficient bone formation for osseointegration of the implant fixtures. This result invites speculation regarding both the mechanism of osseointegration and the minimum surface area of bone-implant interface necessary for achieving and maintaining osseointegration of titanium implants. This patient is periodically examined to determine if the loaded fixtures will remain clinically immobile for a prolonged period. PMID- 1432752 TI - Physical properties and repair bond strength of direct and indirect composite resins. AB - Use of composite resins now includes indirect curing methods. Surface chemistry, repair bond strength, plus location of failure and five physical properties of two direct and three indirect composite resins were determined. There were statistically significant differences in flexural strength of materials and in hardness values. Repair bond strength failures were not significantly different; failures occurred primarily at the interface. Multiple internal reflection spectroscopy confirmed the presence of unpolymerized material after cure in all products. Indirect cure of the direct composite resin increased the degree of cure. PMID- 1432753 TI - Light-cured resin for post patterns. AB - A method of using light-cured acrylic resin as an alternative to the use of chemically-cured acrylic resins with elastomeric impressions for direct post patterns is presented. The GC Unifast LC acrylic resin is a powder/liquid type resin cured by exposure to visible light. The polymerization process has four stages before final curing: slurry, stringy, dough-like (plastic), and rubber like (elastic). Advantages over current direct and indirect procedures include ease of manipulation of the material and no change in laboratory handling procedures. While in the dough-like state, the material can be contoured. In the rubber-like state, it is flexible to disengage from minor undercut areas. PMID- 1432754 TI - Effect of core materials on stress distribution of posts. AB - Severely damaged endodontically treated teeth require the use of a post and core for the retention of the restoration. The choice of material for a post and core and their stress-producing characteristics must be considered by the clinician. Two-dimensional photoelastic analysis of birefringent models was used to investigate the influence of different core materials on the stress distribution of nonthreaded cylindrical posts. Cast posts and cores and prefabricated posts with amalgam and composite resin cores were compared with posts without cores at installation and under two loading conditions. The findings indicate a significant difference between posts with and without cores. It appears that the stiffer core materials can shift the load from the apex to the coronal region. PMID- 1432755 TI - Effects of posts on dentin stress distribution in pulpless teeth. AB - 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. PMID- 1432756 TI - Root fracture in endodontically treated teeth related to post selection and crown design. AB - Standardized plastic analogues simulating an endodontically treated maxillary central incisor root were used to investigate the resistance to root fracture in endodontically treated teeth. Three different post and core systems were used: (1) cast post and core, (2) Para-Post Plus post, and (3) Flexi-Post post. The core build-up material selected in this study was Ketac Silver material, after which a crown preparation was made on each analogue. Two types of preparations were used: a wide chamfer margin (butt-joint) and a wide chamfer margin with a 1.0 mm circumferential bevel. An overcasting was fabricated and was permanently cemented on each preparation. Assemblies were subjected to an increasing lingual oblique force until fracture occurred. Results were tabulated using the analysis of variance (F test) and Student's t test. Beveled preparations with a concomitant final restoration provided a significant increased resistance to root fracture. Furthermore, vertical fracture occurred twice as often with nonbeveled preparations. PMID- 1432757 TI - The retentive and stress distributing properties of split threaded endodontic dowels. AB - A threaded, parallel-sided endodontic dowel that has a longitudinal split was tested to determine its retention and stress distribution properties. Photoelastic stress analysis revealed high installation stresses unless the dowels were counterrotated. Axial loading created stresses at the threads, with elevated coronal and apical stresses. Even higher coronal stresses were recorded with inclined loads, and shorter dowels generated greater stresses than longer dowels. The retentive values were generally lower than those in comparable studies. PMID- 1432758 TI - Evaluation of the fracture resistance of a wrought post compared with completely cast post and cores. AB - The intraradicular fracture of a post and core presents a difficult and often unrestorable situation. Attempts to prevent this problem involved the use of materials with increased physical properties. The use of a preformed wrought post with a core cast to it may provide a more fracture-resistant foundation. This investigation compared a commercially available noble alloy-wrought post that had a gold core cast to it with completely cast specimens from three different alloys. A standard pattern was designed to simulate a post and core that would be used in a tooth of limited length and canal space. Patterns were cast and fixed to custom holding devices. Each specimen was subjected to a shearing force until catastrophic failure in a universal testing machine. Significant differences were noted among the groups. PMID- 1432759 TI - Cement luting thickness beneath porcelain veneers made on platinum foil. AB - Porcelain laminate veneers were made using a platinum foil matrix and were subsequently cemented to mandibular anterior Cymel teeth. Cement film thickness was measured in six predetermined locations. Repeated measures analysis of variance and single degree of freedom contrasts delineated a significant difference between marginal openings at the incisal edge where foil is folded and in four of the other vertical areas (132 versus 74.1 microns). Marginal cement film thickness of veneers made on platinum foil is less than that reported for veneers made on a refractory investment. PMID- 1432760 TI - An evaluation of smear layer with various desensitizing agents after tooth preparation. AB - According to hydrodynamics, any agent blocking the dentinal tubules reduces the flow of fluids and diminishes hypersensitivity. The properties of the desensitizing agents that sponsor tubular occlusion and the barrier efficiency resulting from the interaction of the smear layer with test materials were examined with the scanning electron microscope and energy-dispersive x-ray microanalysis. Selected dentinal desensitizing was accomplished with burnishing procedures, cavity varnish, calcium hydroxide, and topical fluoride. Subjective evaluations were also recorded clinically after tooth preparation. This investigation indicated that the smear layer did not protect against zinc phosphate cement, and that cavity varnish prevented the formation of the smear plugs. The smear layer and plugs were basically composed of calcium and phosphorus, the major ingredients of dentin. PMID- 1432761 TI - Mechanical properties of heat-treated composite resin restorative materials. AB - Clinical methods for heat treating composite resin restorations have been developed. In this investigation, the effect of heat treatments on the diametral tensile strength of composite resin was determined. The composite resin restorative materials were selected according to the manufacturers' suggested use for anterior or posterior teeth, filler particle composition, and light-cured or chemical polymerization. Samples were prepared according to American Dental Association specification No. 27, and heat treatments were accomplished with a Coltene DI 500 oven for curing at approximately 120 degrees C for 7 minutes. Heat treatment substantially increased the diametral tensile strength tested, with the exception of the anterior hybrid particle (p less than 0.05). Composite resins with fine-particle inorganic fillers were significantly stronger than hybrid and microfilled composite resins. PMID- 1432762 TI - Properties of test metal ceramic titanium alloys. AB - Four test alloys were prepared using a high frequency centrifugal casting machine and a ceramic crucible for the development of titanium bonding alloys that can be cast in the ordinary atmosphere. Of these alloys, 10.06% Ti, 78.79% Ni, 9.02% Pd, 1.77% Sn and 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir could be cast by the conventional high frequency centrifugal method; however, 89.18% Ti, 8.75% Ni, 1.03% Pd, 0.28% Sn and 89.81% Ti, 8.15% Ni, 1.01% Pd, 0.18% Sn, 0.67% Ir could be cast only by the argon are melting method. The alloys 10.06% Ti, 78.95% Ni, 9.02% Pd, 1.77% Sn and 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir showed excellent physical and mechanical properties and bonding strengths, surpassing those of the commercial alloys TPW and Unimetal. Concerning the elution of component elements, the amounts of titanium eluted from these alloys were far smaller than those from pure titanium or a Ti-6Al-4V alloy, and nickel elution, which has become an issue in relation to metal allergy, was almost nil in contrast to Unimetal (Ni-Cr alloy). The alloy 9.91% Ti, 78.56% Ni, 9.07% Pd, 1.86% Sn, 0.65% Ir showed properties that indicated its favorable use as an alloy for the bonding of dental porcelain. PMID- 1432763 TI - Use of plastic bar molded casting in the modification of variably expanding investment to compensate for casting shrinkage of nickel-chromium alloy. AB - Trial plastic bar molded castings were compared for accuracy with cast crowns by means of a nickel-chromium alloy, which was used to establish the liquid density of variably expanding investments. The plastic bars were invested to evaluate the change of expansion rate in a wide range of six liquid densities from 0% to 100%, and the distances between the sections were measured before and after casting. Wax crowns were cast to obtain a more detailed relation around 0% expansion at seven liquid densities, and the gaps between the base of the die and the margin of the crown were measured before and after casting. The expansion rates of both castings were calculated and thus were proportional to the liquid density; both regression curves indicated high correlation coefficients. As a result of the statistics of the Student's t-test, the difference between the two methods was not significant. The trial plastic bar was useful in establishing the variably expanding investment for precise casting of artificial crowns. PMID- 1432764 TI - A mathematic model of occlusal adjustment. AB - A mathematic algorithm was developed to calculate mandibular repositioning resulting from occlusal equilibration. A formula to determine the amount of tooth reduction necessary for the adjustment also was derived. PMID- 1432765 TI - Effect of seating force on film thickness of new adhesive luting agents. AB - This study examined the effect of seating force on the film thickness of new adhesive luting agents. The method was in compliance with American National Standards/American Dental Association Specification No. 8 for zinc phosphate cement. The materials tested were zinc phosphate cement, glass ionomer cement, polycarboxylate cement, and a resinous cement with a dentinal bonding agent. All materials were manipulated exactly as described in the manufacturer's instructions, and an electronic gauge with an accuracy of 0.5 micron was used. Each class of material was measured 10 times at six different seating forces. Analysis of variance and multiple comparisons testing disclosed that the seating force and class of material strongly influenced the film thicknesses of luting agents. A mathematical model describing the response of zinc phosphate cement within the range tested was reported. PMID- 1432766 TI - Effect of surface roughness and cement space on crown retention. AB - The effects of varying luting agent space and internal surface roughness with different types of cores and cements were studied. One hundred eighty amalgam and 180 composite cores were cemented into standardized stainless steel retainers. Cores and retainers were divided into 12 groups according to core type, core diameter, and retainer roughness. Each group was further subdivided according to cement, A: zinc phosphate (ZOP); B: resin; and C: glass ionomer cement (GIC). Subgroups were divided into thermal-cycled and nonthermal-cycled groups. Thermal cycling was at 5 degrees to 55 degrees C, repeated 500 times. Cores were separated from their retainers with a compression rod in an Instron testing machine at a crosshead speed of 0.02 cm/minute. Results were as follows: Amalgam cores were most retentive. Resin and ZOP cements were equally retentive with amalgam cores, but GIC was less retentive. Resin cores cemented with resin cement were more than twice as retentive than those cemented with ZOP or GIC cements. Retainers with rough internal surfaces were most retentive. A reduced cement space between core and retainer was most retentive. Thermal cycling reduced retention. PMID- 1432767 TI - Image analysis and occlusion. AB - This study was designed to investigate the measurement of the occlusal contact area (surface) using commercially available equipment and computer programs for image processing and analysis. A stable occlusal record was made using an addition curing silicone rubber putty and was placed on a light source onto which a video camera was focused. This image was digitized and standard thickness records were used to calibrate the appropriate threshold for measurement of contact and near contact surfaces. Differences between individuals and within individuals with and without their partial dentures are large. This method has the potential to be a powerful tool in the study of occlusion. PMID- 1432768 TI - Comparison of load transfer by maxillary distal extension removable partial dentures with a spring-loaded plunger attachment and I-bar retainer. AB - This study photoelastically compared the stress distribution characteristics of two maxillary bilateral distal-extension removable partial denture designs, one using I-bar retention and the other using a semiprecision spring-loaded plunger attachment. Each prosthesis was subjected to vertical and horizontal extension base loads. Comparisons were made from photographic recordings of isochromatic fringe distributions. The two retention designs produced comparable stresses with splinting of abutments for the plunger attachment. The attachment-retained prosthesis proved less stable with some loadings. Stress patterns followed three trajectories in the maxilla. A basis for stress distribution comparisons to other maxillary removable partial denture attachments is established. PMID- 1432769 TI - One-appointment construction of an immediate transitional complete denture using visible light-cured resin. AB - A technique is described for construction of an immediate transitional complete denture in one appointment using self-curing tooth color and visible light-cured resins. Conventional immediate denture therapy may be too prolonged for medically or physically compromised patients. This alternative treatment reduces laboratory, dentist, and patient time, thereby providing a fast and economical service. PMID- 1432770 TI - Treatment of edentulous maxillae with osseointegrated implants. AB - Edentulous maxillae can be restored with implant supported fixed restorations containing denture teeth on a metal framework, implant-retained removable overlay prostheses, or porcelain fused-to-metal fixed prostheses. Esthetics and hygiene access are two important factors in determining the restoration best suited for each patient. Treatment planning considerations and treatment procedures for the various techniques are discussed. PMID- 1432771 TI - Comparative implant research in dogs: a prosthodontic model. AB - One-hundred twenty endosteal dental implants were inserted bilaterally in the mandibles of 30 adult mongrel dogs after bilateral extraction of all premolars. The 120 implants were evenly divided into one- and two-stage systems and included ceramic and titanium cylindrical root-form implants and titanium blade implants. The research design of this investigation divided the 30 animals into 10 groups of three dogs. This article describes an animal model that is useful in evaluating dental implant designs and compares the results with those from humans. In particular, this article delineates the prosthodontic approach appropriate for this model using one- and two-stage titanium implants. Rexillium alloy fixed prostheses were placed on 32 endosteal implants and 16 natural mandibular molar teeth. The implants and prosthetic components of the Sterio-Oss implant system were used. All prostheses are functional with minimal maintenance. To date, after 1-year of follow-up, none of the implants have been lost and none of the fixed prostheses have required recementation or maintenance other than normal hygiene. Histologic and survival data as well as results with other implant systems will be presented in other reports. PMID- 1432772 TI - Effects of osseointegrated implants on psychological and social well-being: a literature review. AB - This article considers three research topics on the social and psychologic aspects of osseointegrated implants. First, the motivations of patients who enter therapy are described. Second, research studies on the psychologic effects of dental implants are critically examined. Although these studies provide consistent evidence in support of osseointegrated implants, there are many issues that make interpretation of results problematic. Finally, some suggestions for future research are made. PMID- 1432773 TI - Effects of environmental factors on maxillofacial elastomers: Part II--Report of survey. AB - Part II of a four-part report presents an international survey that was conducted to determine the most frequently used materials in the fabrication of facial and somatoprostheses. The survey also solicited information about advantages and disadvantages, methods of coloring, and the perceived properties of an "ideal" material. The results of the survey indicated that the majority of prosthodontists and prosthetists are using room temperature-vulcanized silicone products, intrinsically colored with dry earth pigments or artist's pigments. The need for further research in materials for external prostheses was clearly indicated. PMID- 1432774 TI - The mandibular swing-lock complete denture for patients with microstomia. AB - Regardless of cause, the treatment of an edentulous patient with microstomia is difficult and often ingenious. Prosthodontic treatment modalities previously described are reviewed. A new type of prosthesis, the collapsible mandibular swing-lock complete denture, is introduced. The prosthesis incorporates a cast cobalt-chromium framework with a lingual hinge and a conventional labial swing lock. This combination allows the prosthesis to be collapsible while maintaining structural durability. Advantages include ease of insertion and removal while providing maximum coverage for support, retention, and stability. A stepwise technique for the clinical and laboratory phases is described. PMID- 1432775 TI - A multivariate study of patients with temporomandibular joint disorder, atypical facial pain, and dental pain. AB - The multifactorial nature of oral and facial pain was investigated by the collection of clinical and psychologic data from 312 patients with either dental pain, temporomandibular joint disorder, or atypical facial pain. Significant differences between the groups in gender and age distribution, muscle and joint pain, radiographic joint changes, number of remaining teeth, pain duration, and aspects of the patients' perception of pain were evident. In addition, discriminant function analysis clearly differentiated between the three groups on the basis of both clinical and psychologic variables, emphasizing the multifactorial nature of oral and facial pain. PMID- 1432776 TI - Comparison of four different methods of evaluation on axially corrected tomograms of the condyle/fossa relationship. AB - One hundred temporomandibular joints of 50 dry skulls were used to determine whether there was a statistically significantly difference among four different techniques that were employed to assess the condyle/fossa relationship on axially corrected tomograms. A two-way analysis of variance was performed and the results indicated that: (1) a highly significant difference in the condyle/fossa relationship existed (p = 0.002) among the various skulls and (2) no significant difference existed between the four techniques employed to assess the condyle/fossa relationship (p = 1). PMID- 1432777 TI - Evaluation of variables associated with the transverse horizontal axis. AB - The effect of transverse horizontal axis deviations on the vertical and horizontal orientation of maxillary and mandibular members was investigated on a laboratory articulator model. Twelve axis deviations (+30, +25, +20, +15, +10, +5, -5, -10, -15, -20, -25, and -30 mm groups) within a 55 mm dimension model were evaluated. Three trials at each transverse horizontal axis deviation demonstrated significant changes in maxillomandibular orientation after mounting the mandibular member with a standardized intermember mounting record. A linear regression analysis produced an equation for predictive interpolation of anterior posterior shift as a result of axis deviations from +30 to -30 mm. PMID- 1432778 TI - Spacer made from a visible light-cured resin for processing denture soft liners. AB - When soft lining materials are used in complete dentures it is important to control their thickness and increase the probability of their staying in the denture base. A spacer made of light-curing denture base material makes it possible to do both of these things. The denture base resin is packed against the hard light-cured spacer and can be partially cured. The cured spacer will not flow or be displaced and can be easily removed to allow an even space for packing the soft lining material. PMID- 1432779 TI - A flasking technique for microwave processing of silicone prostheses. AB - Polyvinylchloride plumbing parts provide a readily available source of material to use in making facial prostheses. Inexpensive pipe fittings (end cap attachments and closet flanges) can be combined to provide a durable container for stone molds that can be tightened in a strong curing press. The entire unit can be cured in a microwave oven in 30 minutes. PMID- 1432780 TI - Making a coping for an esthetic veneer crown. AB - Esthetic veneer crowns should be waxed to full contour before the veneer surface is cut back. This procedure ensures that patterns and metal copings will have the proper contours. A technique is described for making a coping that has an ideal thickness of 0.3 to 0.5 mm, that is stable, and that is unlikely to fracture. PMID- 1432781 TI - A soft tissue simulated cast for implant prosthesis. AB - A master cast that simulates the mucosa around implant fixtures and abutments facilitates implant prosthesis fabrication. It is helpful if this simulation is not altered during laboratory procedures. A technique is described for a master cast that includes a removable mucosal component. This technique can be applied when either implant or abutment analogs are positioned in the cast. PMID- 1432782 TI - Making a provisional crown under a clasp of an existing removable partial denture. PMID- 1432783 TI - Protecting the finish of stone dies during trimming. AB - This procedure is quick, easy, and inexpensive. It prevents damage to the die during trimming and does not alter the integrity of the die. PMID- 1432784 TI - Mixing irreversible hydrocolloid with no bubbles or hassles. PMID- 1432785 TI - Use of a maxillary tray to make an alginate impression for patients with large bilateral mandibular tori. PMID- 1432786 TI - Duplication of interim speech aid for definitive impression tray fabrication. AB - A wax tray is stable and easily relieved if overextended. Unusual tray undercuts or angles needed for the partial resection patient need not be eliminated before the impression procedure. Relief of these undercuts is necessary with acrylic resin trays to ensure separation from the final stone cast. Because the wax tray is separated easily from the prosthesis during the boil-out, it is not necessary to "burn" or grind acrylic resin from the framework. The tray shape is duplicated from the existing interim prosthesis on the nasopharyngeal and oropharyngeal side. An arbitrarily shaped acrylic resin tray may be grossly overextended and require time-consuming clinical adjustments. An underextended tray on the nasopharyngeal side will not carry or support the impression material around or through the residual soft palate remnant. A tray that closely approximates the final prosthesis will allow use of a tissue conditioner final impression without need for border molding (Fig. 2). Duplicating the oropharyngeal side of the interim speech aid duplicates the previously established plane that is compatible with the tongue. The author has used this technique successfully for eight total and five partial soft palate resections. A cleft palate speech aid prosthesis has also been made with this technique. PMID- 1432787 TI - A modeling hot knife used to remove palates from waxed trial dentures. PMID- 1432788 TI - An alternate method of packing casts for transport. PMID- 1432789 TI - Interim treatment of a patient with eroded maxillary dentition: a clinical report. PMID- 1432791 TI - Polyvinyl siloxane impression materials: a review of properties and techniques. AB - Polyvinyl siloxane impression materials have been shown to have excellent properties as impression materials; however, they are sensitive to manipulative variables. Several methods of using very high viscosity (putty) materials to form "trays" to obtain uniform bulk of the wash impression are described, and the disadvantages of each of these techniques is pointed out. It is recommended that for best results acrylic resin custom trays should be used routinely. The interaction of polyvinyl siloxane materials with latex products is also discussed and problems that this inhibition can cause are stated. Suggestions to avoid this interaction are outlined. One of the disadvantages of the impression materials is that it has a relatively short working time. Refrigerating the material will increase working time without affecting accuracy. PMID- 1432790 TI - An experimental porcelain repair system evaluated under controlled clinical conditions. AB - Twenty metal ceramic crowns on upper premolars in 12 patients were purposely fractured before seating with temporary cement. The fractured crowns were repaired in situ with an experimental porcelain repair system. The initial results were satisfactory both esthetically and functionally. However, only 50% of the repairs were intact by the end of the 12-month follow-up period. The system is considered to be suitable only for intermediate repairs of metal ceramic crowns that are in occlusal contact. PMID- 1432792 TI - Effect of fluoride varnish on the retentive strength of provisional crowns luted with various temporary cements. AB - The retention of temporary crowns was studied with the use of a fluoride varnish (Duraphat) combined with various temporary cements. The mixture of Duraphat varnish and cement improved retention, with the exception of Opotow cement. Applying Duraphat varnish to the tooth surface before cementation enhanced the retentive strength of Tempbond, weakened the retention of Freegenol, but had no effect on Opotow cement. A "transfer effect" was observed, inasmuch as the Duraphat varnish encouraged adherence of the cement to the tooth structure rather than to the temporary crown. PMID- 1432793 TI - Use of luting agents with an implant system: Part I. AB - When removal of the provisionally cemented superstructure from a cemented abutment becomes necessary, the retentive strengths of the abutment/fixture and superstructure/abutment luting agents become important considerations. This study compared the retentive strengths of castings cemented to machined titanium implant abutments and to a human premolar with three provisional luting agents. Also tested were the retentive strengths of cast noble metal implant abutments cemented into titanium fixtures with three permanent luting agents both dry and after storage in 0.9% physiologic saline for 30 days at 37 degrees C. No significant differences (alpha < 0.05) were noted in retentive values between the cemented castings on the titanium abutments and the natural tooth. The Temp Bond zinc oxide-eugenol luting agent exhibited a lower mean retentive strength than the IRM reinforced zinc oxide-eugenol and Life calcium hydroxide luting agents. Ketac Cem glass-ionomer cemented abutments that were stored in saline exhibited a significantly higher mean retentive strength than abutments cemented with either Core Paste or Resiment resin luting agents. On the basis of results from this study, it may be concluded that superstructures provisionally cemented with Temp Bond, IRM, or Life luting agents may be removed from implant abutments without disturbing the abutment/fixture or implant bond. PMID- 1432794 TI - Change in occlusal height resulting from placement of pit and fissure sealants. AB - This in-vitro study was done to identify the amount of change in occlusal height resulting from standard sealant application technique and to determine whether this change was uniform for both a filled and an unfilled sealant material. Twelve dental hygienists experienced in sealant technique each applied 10 filled sealants and 10 unfilled sealants in standardized artificial teeth mounted in a dentiform and mannikin setup in a dental unit. The teeth were measured with a digital caliper before and after sealant placement. Measurements were from a predetermined point at the apical area of the teeth to the depth of the central fossa. For the sample of 240 teeth, the mean sealant thickness was 0.43 +/- 0.20 mm. When the data for the filled and unfilled sealants were examined separately, the means were 0.47 +/- 0.23 mm and 0.38 +/- 0.16 mm, respectively. A t-test indicated a significant difference at p < 0.001. Analysis of variance revealed significant interoperator differences in sealant thickness (p < 0.01). PMID- 1432796 TI - Epinephrine absorption from commercial gingival retraction cords in clinical patients. AB - Absorption of epinephrine from commercial gingival retraction cords was measured in vivo under clinical conditions. The amount of epinephrine absorbed was estimated by measurement with fluorospectrophotometry of the amount of dl epinephrine remaining in the cords after they were removed and subtracting this value from the dl-epinephrine concentration in matching control cords. All cords lost substantial amounts of epinephrine while in the sulcus, with individual losses ranging from 64% to 94%. An average 71 micrograms of l-epinephrine was absorbed per inch of two-ply cord, and extreme variability in the dl-epinephrine concentration for individual segments of commercial cord was noted. In addition, the cords did not contain the concentration of epinephrine (500 micrograms/inch) listed on the package label but instead had a mean dl-epinephrine concentration of 225.5 micrograms/inch. PMID- 1432795 TI - Alterations in human enamel surface morphology following vital bleaching. AB - Extracted intact human teeth (n = 4) were treated for 30 days by three protocols: Home 1 (Proxigel, n = 4) for 8 hours daily, Home 2 (White & Bright, n = 4) for 24 hours with 3 minutes of stannous fluoride gel, or an Office protocol (n = 4) using 30% hydrogen peroxide (Superoxol) warmed by a high-intensity light while the controls remained untreated. "Home" bleaching agents contain approximately 10% carbamide peroxide. After treatment, the coronal surfaces were examined with a scanning electron microscope (SEM) at 2000 power magnification, and the surface topography was measured by a profilometer. The SEM photomicrographs of the controls and office-treated groups were similar to previously reported descriptions, while the home bleached surfaces appeared similar to each other. Profilometric analysis was used to examine surface roughness and surface waviness. Mean surface roughness in microns was: control, 1.9; Home 1, 0.6; Home 2, 0.9; and Office, 0.6. Surface waviness was ranked control > office > Home 1 = Home 2. Enamel surface alterations were evident after the three bleaching methods. The differences between the office and home-treated surfaces were unrelated to the pH of the bleaching agents. PMID- 1432797 TI - Postcementation marginal fit of a new ceramic foil crown system. AB - The in vitro marginal fit of a new foil crown was investigated. Ten standardized polycarbonate master dies filled with 30 wt% carbon having a 90-degree butt joint margin were used to evaluate the marginal fit of Sunrise porcelain foil crowns. The crown specimens were made on stone dies and treated with three coats of die spacer. After fabrication, they were adjusted, cemented with zinc phosphate cement to their respective master dies with 5 kg loading for 10 minutes and stored in water. A Gaertner traveling microscope was used to measure the marginal fit of each specimen. Readings were recorded at five locations randomly marked but equally dividing the margin on each crown, and the overall mean for the crowns was then calculated. The results from the 50 areas revealed a mean marginal discrepancy of 25.3 microns, and this compared favorably with the discrepancies reported for other ceramic crown systems. PMID- 1432798 TI - Transitional use of a tube/sleeve dowel on endodontically treated canines. AB - This technique affords a simplified alternative to more complicated and expensive treatment of periodontically compromised teeth. It provides the patient with an extended-term prosthesis attached to a single or multiple retained canine. A disadvantage of this technique is that poor hygiene may result in caries or further periodontal breakdown. The internal liner of the cemented tube/sleeve will accumulate food particles if the patient does not keep the prosthesis in place during all times of food ingestion and does not periodically irrigate the internal tube/sleeve. PMID- 1432799 TI - The effects of cold treatment on the physical properties of stainless steel and titanium alloy endodontic posts and instruments. AB - This study determined whether cold treatment at -96 degrees C affected the mechanical properties of different compositions and sizes of Flexi-Post systems, various sizes of dental reamers, and external wrenches. The experiment was divided into eight groups. The four control groups were untreated and consisted of (1) 50 stainless steel posts, (2) 40 titanium posts, (3) 50 stainless steel reamers, and (4) 10 stainless steel external wrenches. The four experimental groups were cold treated once and twice and included (1) 100 stainless steel posts, (2) 80 titanium posts, (3) 100 stainless steel reamers, and (4) 20 stainless steel external wrenches. The bending or breaking forces were tested on a universal testing machine. Stainless steel Flexi-Post dowels, stainless steel reamers, and external wrenches all showed a significant (ANOVA) (p < 0.05) increase in strength as a result of the single and double cold treatment. Titanium posts showed no strength increase following a single cold treatment, while they were weakened by a double cold treatment. PMID- 1432800 TI - Influence of circadian periodicity on reproducibility of centric relation records for edentulous patients. AB - Complete dentures were made for 30 edentulous patients. The patients were divided into three groups and the dentures were remounted twice on the same day in a Vericheck instrument. The dentures for 10 patients were remounted twice in the morning (AM group), for 10 patients twice in the afternoon (PM group), and for 10 patients once in the morning and again in the afternoon (AM-PM group). Changes in position between the interocclusal records were measured on both the right and left horizontal X and Y axes and the sagittal Y and Z axes. No significant changes were noted when horizontal versus sagittal or right versus left positions were compared, but significant changes were noted between the AM versus AM-PM time groups, and between the PM versus AM-PM time groups. PMID- 1432801 TI - Load transfer by a maxillary distal-extension removable partial denture with cap and ring extracoronal attachments. AB - This study photoelastically compared the stress distribution characteristics of maxillary, bilateral, distal-extension removable partial dentures retained by light and heavy ERA extracoronal attachments. One prosthesis included supporting rests and the other had no rests. Both designs were tested with and without abutment splinting. The most favorable stress distributions were obtained with light retention elements, supporting rests, and splinting of the abutments. In this configuration the attachment prosthesis compared favorably in stress distribution with the maxillary I-bar retained removable partial denture in a previous study that used a comparable maxillae model. PMID- 1432802 TI - Force-deformation properties of artificial and natural foods for testing chewing efficiency. AB - The force-deformation characteristics of two artificial test foods (Optosil and Optocal) for measurements of food comminution during mastication were investigated in a bite simulator and compared with those of carrots and peanuts. The influence of cusp geometry was evaluated by use of a flat plate and three cusp forms. The forces at the yield point were lower for Optocal than for Optosil artificial test food. The forces needed for Optocal overlapped those needed for carrots and peanuts. The natural foods showed more variation in the force and percentage of deformation at the yield point than the artificial foods. The artificial foods reflected the differences in cusp form better than did the natural foods. The use of artificial foods fulfills a need for standardization and warrants consideration in studies of mastication. PMID- 1432803 TI - The effect of removable partial denture framework design on gingival inflammation: a clinical model. AB - A clinical trial using the experimental gingivitis model developed for periodontal clinical research was performed to evaluate the effect of a removable partial denture mandibular major connector design on the surrounding gingival tissues. A comparison of the state of health of adjacent gingival tissues was made between the linguoplate (control) and cingulum bar (test) major connectors. Clinical parameters were recorded in a single-blind crossover experimental gingivitis trial. Subjects were brought to a level of optimal gingival health and then randomly assigned to use one framework design while refraining from any oral hygiene. Measurements were made at 7-day intervals for 21 days. The subjects were returned to optimal oral health and repeated the experimental period with the alternate design. Results showed a greater increase in mean gingival inflammation with the control than with the test removable partial denture, suggesting that the cingulum bar has fewer detrimental effects on gingival tissues than the linguoplate major connector. Results of this study suggest that the experimental gingivitis model can be a useful and valid system for studying the potential effects of a removable partial denture design on surrounding oral tissues. PMID- 1432804 TI - In vitro evaluation of Candida albicans adherence to soft denture-lining materials. AB - The adherence of Candida albicans to seven commercial soft denture-lining materials was studied in vitro with BCA protein assay reagent. A good correlation was observed between the amount of protein in yeast cells and the number of yeasts (r = 0.993, p < 0.01), and it was revealed that the adherence of C. albicans to bare surfaces of these soft denture-lining materials correlated well with their relative hydrophobic properties (r = 0.905, p < 0.01); thus there was consistency with the thermodynamic theory. These results combined corroborated the accuracy of this method. To know the effect of pellicle on fungal adherence, the adherence of C. albicans to saliva-coated samples was examined. It was revealed that neither the amount of protein adsorbed by substrates nor the adherence of yeast to saliva-coated substrates correlated with the relative hydrophobic properties of these samples, suggesting that factors other than hydrophobic interaction play an important role in the adherence of C. albicans to pellicle-coated soft liners and tissue conditioners. PMID- 1432805 TI - Generic terminology for endosseous implant prosthodontics. AB - Implant dentistry has become an integral treatment modality in the restoration of the complete and partially edentulous patient. Most practitioners have been educated by manufacturer-sponsored courses oriented to the use of a specific implant system. The ever-increasing number of implant systems has made the names of many implant components product-unique and confusing. Fortunately, a prosthetic continuity exists between most implant systems. A generic terminology for endosseous root-form prosthodontics is presented that allows effective communication between members of the profession. PMID- 1432806 TI - The three-dimensional bone interface of an osseointegrated implant: a method for study. AB - To clarify the three-dimensional bone structure around a plasma-sprayed hydroxyapatite-coated endosseous dental implant, bone contact with the implant at 75 microns intervals was evaluated. Based on digitized data, three-dimensional graphics of the bone around the implant was clearly shown. These graphics provide adequate information on the bone-implant interface and also suggest development of a realistic finite element model. PMID- 1432807 TI - Cantilever rests: an alternative to the unsupported distal cantilever of osseointegrated implant-supported prostheses for the edentulous mandible. AB - Mandibular prostheses supported by implants placed between the mandibular foramina restrict the length of the distally cantilevered components to minimize torque-related stress to the supporting implants. Additional posterior implants used as abutments with rigid attachments better distribute occlusal forces and reduce cantilever torque to the anterior implants. Because of the phenomenon of mandibular flexure, these posterior implants could be subjected to stress-induced microdamage to the bone-implant interface. The use of posterior abutments for support of the cantilever without connection reduces the potential hazard of stress-induced microdamage. PMID- 1432808 TI - Effects of environmental factors on maxillofacial elastomers: Part IV--Optical properties. AB - The optical properties of four currently used and two recently introduced maxillofacial prosthetic materials were evaluated after the materials were subjected to the following seven environmental variables: natural weathering; normal aging; two types of adhesives; two types of cleaning agents; and cosmetics. Optical density and color changes were evaluated. The currently used silicones Silastic 4-4210 and Silastic 4-4515, Medical Adhesive type A material, and polyurethane all showed more changes in color and optical density than the newly introduced silicone A-102 material. PMID- 1432809 TI - New diagnostic and therapeutic mechanical device. AB - A new device is described that may be used (1) diagnostically to determine the relationship of the occlusion to tenderness in the lateral pterygoid and other muscles of mastication; (2) to relieve ischemic muscle tenderness; (3) to assist in the reduction of articular clicks; and (4) as a positioning device for the registration of physiologic interocclusal relations. The rationale for the causal relationship between the occlusion and lateral pterygoid muscle tenderness is explained. PMID- 1432810 TI - Biomechanical model of the human mandible: a hypothesis involving stabilizing activity of the superior belly of lateral pterygoid muscle. AB - A new biomechanical analog for the human mandible is proposed. The biomechanics of the human mandible can be explained by a simple support model, where muscular forces are produced by the masseter, medial pterygoid, temporal, and superior lateral pterygoid muscle components, and reaction forces are produced by the occlusal surfaces and condyle. All forces are resolved into components orthogonal and parallel to the temporal articular plane (articular eminence). In this model, one component of muscular forces is parallel to the temporal articular plane. The influence of the inclination of the occlusal plane, the inclination of the temporal articular plane, the position of the resultant of the occlusal reactions, and the relative contribution of the different jaw elevator muscles on the parallel and orthogonal components are evaluated according to a computer model of the system. The muscular force parallel to the temporal articular plane may be produced by the superior lateral pterygoid muscle, which during clenching acts as a stabilizer of the mandibular condyle to prevent posterior dislocation and compression of nonarticular tissues. PMID- 1432811 TI - Color stability of long-term soft denture liners. AB - The use of resilient denture liners in complete denture construction has become increasingly popular for providing comfort for denture wearers. The primary disadvantage of these materials is that the physical and mechanical properties change rapidly with time in a service environment. The purpose of this study is to evaluate the color stability of five commercially available soft denture liners as a function of accelerated aging. Color measurements were made before aging with a colorimeter and data processor. The samples were then weathered for 100 hours in an accelerated aging chamber in the presence of a xenon ultraviolet visible-light source, an intermittent water spray at 110 degrees F, and 90% humidity. After aging, color measurements were made again and color differences (delta E) were calculated. Results were statistically tested with analysis of variance and Scheffe intervals were calculated at 0.96. It was concluded that accelerated aging can be used to evaluate color stability of soft denture liners. PMID- 1432813 TI - Making an instrument for smoothing the detailed occlusal anatomy of a wax pattern. AB - A smooth wax pattern is imperative to reduce the polishing time of the subsequent casting. The detailed occlusal anatomy is often the most difficult portion of the wax pattern to smooth. This article describes a procedure for making a device that can be used to smooth the detailed anatomy of a wax pattern. It also describes how to use the device. PMID- 1432812 TI - The facial soft tissue profile of the southern Chinese: prosthodontic considerations. AB - A simple photographic setup was established to produce standardized life-sized black and white prints of Southern Chinese adults. Facial soft tissue profile analysis was performed on 28 men and 31 women aged 19 to 30, dentate Chinese, having class I occlusion and originating from Guangdong province. The facial profile values studied included the profile convexity, the interlabial contour, the nasolabial contour, the columella and upper lip inclination angles to the true horizontal, and the relative positions of upper and lower lips from the Esthetic plane. Data obtained were compared with those from previous Caucasian studies and other accepted empirical values. The lower third of the face presented the greatest ethnic difference: the interlabial contour was more convex and the upper and lower lips were more protrusive among the Southern Chinese. The widely-used standard of a right-angled nasolabial contour proved to be applicable among the Southern Chinese adult males. However, a more obtuse nasolabial angle, almost 100 degrees, occurred among the women. PMID- 1432814 TI - Adhesion properties of resilient lining materials bonded to light-cured denture resins. AB - This study compared the adhesive strength of three resilient denture lining materials with different chemical compositions when bonded to visible light-cured (VLC) denture base resin. Shear adhesive strength was evaluated using a simple overlap-joint model. Three different bonding agents were used and the effect of water on the bonding strength was evaluated by a series of samples tested after storage for 4 months. The findings showed that all of the lining materials were acceptable for clinical use but that water storage reduced their bond strength to VLC resin. PMID- 1432815 TI - Special matrix for use with glass ionomer in restoring molars with Class V root surface lesions. AB - A simple method of making a custom matrix for molar root lesions has been described. The matrix provides anatomic form to the restoration and reduces the chairside time required to contour and finish the restoration. PMID- 1432816 TI - A noncontaminating visual aid and indicator for porcelain additions to ceramometal restorations. PMID- 1432817 TI - An atraumatic denture base design for a tooth-bound mandibular removable partial denture. AB - This technique applies accepted fixed prosthodontic pontic design to the denture base design of a tooth-bound removable partial denture. Patient feedback emphasizes the comfort and lack of bulk of the prosthesis compared with a removable partial denture of conventional design placed simultaneously. PMID- 1432818 TI - A laminating procedure for thermoformed mouthguards. PMID- 1432819 TI - Multiple custom anterior guide tables made from a single stock incisal table. PMID- 1432820 TI - Easy control of thermoplastic border molding materials. PMID- 1432821 TI - Removal of a fractured implant hygiene insert. PMID- 1432822 TI - The mesial rest I-bar clasp. PMID- 1432823 TI - Dilemma of scientific knowledge versus clinical management of temporomandibular disorders. PMID- 1432824 TI - Evaluation of marginal adaptation of all-ceramic crowns and metal ceramic crowns. PMID- 1432825 TI - Urinary tract infection--a dangerous and unrecognised forerunner of systemic sepsis. PMID- 1432826 TI - Use of nitroglycerin ointment to prevent hypertensive response during electroconvulsive therapy--a study of 50 cases. AB - Fifty patients of either sex, aged between 20 and 60 years undergoing electroconvulsive therapy were included in our study. Each patient was used as his/her own control. We observed the cardiovascular changes without nitroglycerin ointment in the first sitting and in the next sitting with the application of 2 inches of 2% nitroglycerin ointment 45 min before the electroconvulsive therapy. Arterial blood pressure and heart rate increase during electroconvulsive therapy can be effectively attenuated by application of 2 inches of 2% nitroglycerin ointment 45 min before the electroconvulsive therapy (p < 0.001 and p < 0.01 resp.). This may be especially beneficial for patients who are at increased risk of myocardial ischemia and stroke. PMID- 1432827 TI - Evaluation of two methods employed for cervical ripening. AB - The study evaluates breast stimulation and oxytocin infusion as methods for cervical ripening in patients where an obstetric indication for induction of labour exists. Forty patients with a Bishop score of 5 or 6 were randomly selected for either breast stimulation or oxytocin infusion. In a similar group of 20 cases, no method was employed. The Bishop score improved in 41.2% of cases where breast stimulation was used as compared to 75% where an oxytocin infusion was given. Three foetal deaths in the breast stimulation group brought the study to a stop after 17 cases. Cervical ripening with an oxytocin infusion drip appears to be a better method since infusion dosage can be precisely controlled making the technique more predictable and reliable. Though breast stimulation is effective in ripening the cervix, it may be used only in cases of intrauterine foetal death as it may otherwise adversely affect foetal outcome. PMID- 1432828 TI - Analysis of 105 uninodular goitres. AB - Data on 105 solitary thyroid nodules, confirmed at surgery to be solitary, is presented. Six (5.7%) were malignant, 4 papillary and 2 follicular. The sensitivity and the specificity of 131I radionuclide thyroid scan (n = 90) were 100% and 24% respectively. Similarly, the sensitivity and specificity of fine needle aspiration cytology (n = 65) was 75% and 100% respectively. In both instances, the "gold standard" was the histopathology of the surgically removed nodule. In order to avoid unnecessary surgery, without missing malignancy, we would recommend the combination of radionuclide thyroid scan and FNAC for investigation of solitary thyroid nodules. PMID- 1432829 TI - Significance of negative hysteroscopic view in abnormal uterine bleeding. AB - Ninety six cases of abnormal uterine bleeding were evaluated by both panoramic hysteroscopy and dilatation and curettage. The indications for hysteroscopy included postmenopausal bleeding, infertility with abnormal bleeding, abnormal bleeding and suspected leiomyoma with bleeding. Twenty three patients had abnormal hysteroscopy findings. Hysteroscopy diagnosed endometrial polyp and submucus leiomyoma with 100% accuracy. In 17 cases, the results of hysteroscopy and curettage were in agreement and hysteroscopy revealed more information than curettage in 6 cases. Among the remaining 73 cases with 'negative' hysteroscopic view, an abnormality was detected by tissue sampling in only 2 patients. The specificity and positive predictive value of hysteroscopy is 100%. The sensitivity of hysteroscopy was greater (92%) than that of curettage (76%) and the negative predictive value of hysteroscopy was 2.8%. Thus, panoramic hysteroscopy may prove to be superior to curettage in making an accurate diagnosis of intrauterine pathology. PMID- 1432830 TI - Hyperferritinemia in pregnancy induced hypertension and eclampsia. AB - A study of serum iron and ferritin levels in Indian women with pregnancy induced hypertension (PIH) (mild/severe) and eclampsia compared with controls of similar gestational ages, revealed that mean serum iron was elevated slightly in PIH and significantly in eclampsia as compared to controls. Mean ferritin levels were significantly elevated both in PIH and eclampsia as compared to controls indicating that ferritin measurement in PIH and eclampsia would not reflect iron nutritional status. Lack of significant changes in liver enzymes and in hemoconcentration in PIH and eclampsia indicate that liver damage and altered hemodynamics only play a partial role in causing hyperferritinemia. Possible role of placental ferritin, being released as a result of placental damage in these conditions seems to be an area needing further research. PMID- 1432831 TI - Temporary intravascular shunts for peripheral vascular trauma. AB - Polyvinylchloride (PVC) disposable endotracheal suction catheters were successfully used as temporary intravascular shunts in 5 patients of popliteal artery trauma. These simple shunts should be used routinely in such conditions to immediately re-establish blood supply to the ischaemic limb particularly in patients of polytrauma where systemic anticoagulation is contraindicated. This avoids the inherent delay prior to vascular repair and reduces the incidence of irreversible ischemia. PMID- 1432832 TI - A comparison of three media for isolation of Nocardia species from clinical specimens. AB - The study was carried out to compare the efficacy of three media namely Modified Thayer Martin medium, McClung's carbon free broth with paraffin bait and paraffin agar in isolating Nocardia species from clinical specimens. Two hundred and seventy six clinical specimens from 245 cases were studied which included cases of bronchopulmonary and systemic infections and cases of mycetoma. Paraffin agar was found to be an inexpensive and selective medium for isolation of Nocardia species when compared with Modified Thayer Martin medium and paraffin bait techniques. PMID- 1432833 TI - Detection of serum antitrichomonal antibodies in urogenital trichomoniasis by immunofluorescence. AB - Trichomonas vaginalis is a frequently encountered genital pathogen in both males and females. In females, vaginitis due to this parasite is one of the most common manifestation. The indirect fluorescent technique (IFA) test was carried out to detect antitrichomonal antibodies in 370 female patients using whole cell antigen. Seventy one (19.18%) gave positive reaction for either of the class IgG, IgM and IgA antibodies. The level of the IgG class antibodies was found to be higher i.e. 58 (81.69%) than IgM 11 (15.27%) antibodies, which may be suggestive of past infection or a prolonged manifestation by the organisms. PMID- 1432834 TI - Endovascular treatment of cerebral arteriovenous malformations. PMID- 1432835 TI - Leiomyoma of the female urethra. PMID- 1432836 TI - Adenocarcinoma of the colon in a child. AB - A rare case of a 10 year old boy presenting with history of lower GI bleeding for one year and acute intestinal obstruction was diagnosed as adenocarcinoma of the colon on exploration. One year follow-up after radical colectomy did not show any recurrence. PMID- 1432838 TI - Non-A non-B hepatitis induced aplastic anemia. PMID- 1432837 TI - Benign neonatal pneumoperitoneum--an enigma. AB - A case of neonatal pneumoperitoneum in absence of a bowel perforation or intrathoracic pathology has been reported. The cause of such a rare manifestation remains to be established. PMID- 1432839 TI - Radionuclide assessment of peritoneovenous shunt patency. AB - Denver shunt patency can be easily assessed by sequential scintigraphy with a Gamma camera after an intraperitoneal injection of 99mTc sulphur colloid. If the shunt is patent, the tracer will be seen throughout the shunt upto it's opening into the right atrium. The following case report illustrates the application and usefulness of this procedure. PMID- 1432840 TI - Anaesthetic management in removal of a huge ovarian cyst. AB - A patient with a huge ovarian cyst weighing 38 kg was operated successfully with utmost care to avoid all possible intra and postoperative complications. The same has been presented and the salient features of management have been discussed. PMID- 1432841 TI - Solitary retroperitoneal angiofollicular lymph node hyperplasia. AB - The fine needle aspiration cytology (FNAC) and ultrasound radiologic features of a solitary retroperitoneal angiofollicular lymph node hyperplasia (AFLNH), hyaline vascular type are described. Based on a combination of the two, this diagnosis can be suggested in the differential diagnosis of a retroperitoneal mass. PMID- 1432842 TI - Posterior midline cervical fetal cystic hygroma. AB - Posterior midline cervical cystic hygromas (PMC) are frequently found associated with chromosomal aberrations and usually do not survive. The present report illustrates diagnosis of this condition by sonography in an 18 weeks old fetus and an amniocentesis revealed 45 x0 karyotype and increased concentration of alpha-fetoproteins. Pregnancy was terminated in view of Turner's syndrome. The etiology and natural history of the condition is reviewed. PMID- 1432843 TI - Amegakaryocytic thrombocytopenic purpura. PMID- 1432844 TI - Paranoid and nonparanoid schizophrenic processing of facially displayed affect. AB - It was proposed that differences between paranoid and nonparanoid schizophrenics in the processing of affective information may reflect underlying differences in their schema for emotion-laden information. Performances of 14 paranoid schizophrenics, 13 nonparanoid schizophrenics, and 15 matched controls were compared on a facial affect judgment task, and a matched control task comprising geometric figures largely devoid of emotional information. Subjects were required to rate friendliness, select an emotion label, and subsequently to remember the stimuli. Nonparanoids were deficient in overall labeling of facial affect, suggesting a weak cognitive schema for emotional information. The paranoids were particularly more accurate than the nonparanoids at labeling the negative facial affects, suggesting well-developed negative emotional aspects in their cognitive schema. Unexpectedly, nonparanoids relative to paranoids displayed a greater memory deficit in the recognition of geometric figures than in the recognition of faces. The nonparanoid deficit suggests these subjects may have poorly organized schema for remembering less structured nonverbal information. The findings support the idea of fundamental cognitive processing differences between paranoid and nonparanoid schizophrenia. PMID- 1432845 TI - A clinical and biological validation of the DSM-III melancholia diagnosis in men: results of pattern recognition methods. AB - Pattern recognition methods were carried out on a sample of 80 depressed men, assessed by means of 14 items relevant to depressive symptomatology of the Structured Clinical Interview for DSM-III-R. 1985 edition (SCID). A cluster analysis generated two classes, which were described as a vital (n = 35) and a nonvital cluster (n = 45). Vital depressives were characterized by psychomotor disorders, loss of energy, cognitive disturbances, a distinct quality of mood, early morning awakening and nonreactivity (the "vital" symptoms). Our findings support the descriptive validity of the DSM-III melancholia diagnostic category, although the DSM-III criteria are too conservative and include nonrelevant symptoms (e.g., diurnal variation, anorexia-weight loss) whilst excluding some important items (e.g., loss of energy, cognitive disorders). Vital depressed men were significantly older, more severely depressed and they exhibited biological disturbances (abnormal dexamethasone suppression test, lower basal thyroid secreting hormone) as opposed to nonvital depressives. There are several arguments to support the possibility that both clusters constitute relevant stages in the overall severity of illness continuum, whilst showing qualitative differences with regard to the vital symptoms. In other words, both clusters are continuous categories within the overall severity of illness continuum and form discrete categories with regard to the vital symptoms. By merging the dimensional and categorical hypotheses, we were able to construct a new integrated threshold model: unipolar depression in men is probably a homogeneous disease with reference to overall severity of illness, but--as severity increases--vital symptoms emerge, grouping together into a distinct profile, i.e., vital depression. PMID- 1432846 TI - The relationship of personality to mood and anxiety states: a dimensional approach. AB - This study evaluates the relationship of personality to mood and anxiety states in a sample of 50 psychiatric out patients. In order to overcome arbitrariness inherent in categorical diagnoses of affective, personality and anxiety disorders, we use a dimensional approach to personality, mood and anxiety. According to our results, mood and anxiety states affect personality domains differentially. Namely, relatively large portions of personality and behavior, such as higher-order traits of novelty seeking and reward dependence, seem independent from mood and anxiety states. In contrast, the higher-order dimension of harm avoidance and its corresponding lower-order traits reflect changes in mood and anxiety to a much greater extent. Both the likelihood that large portions of personality may be independent from current mood and the likelihood that some precisely delineated personality domains tend to change simultaneously with current mood may improve our understanding of the relationship of personality to emotionality and affective disorders. PMID- 1432847 TI - Distribution of peripheral lymphocytes in Alzheimer patients and controls. AB - Deficient immunoregulation has been postulated to play a role in the pathogenesis of Alzheimer's dementia. Recently, lymphopenia was reported to be more prevalent in Alzheimer patients than in control subjects. In addition, a decreasing number of total lymphocytes was found to be significantly correlated with increasing severity of dementia. In an attempt to replicate these findings, we studied 55 Alzheimer patients and 41 healthy controls of comparable age and gender, but found no significant difference in the distribution of total lymphocytes between these groups. Furthermore, total lymphocytes were not significantly correlated with dementia severity. Our findings, therefore, do not lend further support to an immune hypothesis for Alzheimer's dementia. PMID- 1432848 TI - Perception of breath components by the tropical bont tick, Amblyomma variegatum Fabricius (Ixodidae). II. Sulfide-receptors. AB - Wall-pore sensilla in the capsule of Haller's organ on foreleg tarsi of the tick, Amblyomma variegatum, show multicellular responses upon stimulation with human and bovine breath. Filtering breath through charcoal removes the stimulant for some of these receptors. Analysis by gas chromatography coupled with olfactory sensillum electrophysiological recordings indicates that an ethanol extract of the breath components trapped on charcoal contains a major stimulant eluting at the same retention time as H2S. Two types of H2S-sensitive receptors have been identified. They are housed in separate sensilla, and are called sulfide-receptor 1 and 2. Although, both receptor types are characterized by a high sensitivity to H2S with an estimated threshold of ca. 0.1 ppb and a response range covering 5-6 log orders of magnitude, their overall response to sulfides and mercaptans is nevertheless dissimilar. The type 1 receptor fires slightly more upon stimulations with H2S than type 2, whereas ethylmercaptan induces a stronger response from type 2, and dimethyl sulfide activates only receptor 2. In a bioassay, H2S tested at concentrations of ca. 0.02 ppm and 1 ppm equally arouses 60% of resting ticks. Two-thirds of these ticks quest the air with their first pair of legs, and the remainder start active search. By contrast, H2S at ca. 1 ppm in a mixture with CO2 severely diminishes the locomotor stimulating effect of CO2. PMID- 1432849 TI - Focusing and accommodation in the brown kiwi (Apteryx australis). AB - Brown kiwis are an endangered species of nocturnal, flightless birds which are native to New Zealand. The resting focus of two specimens has previously been studied by retinoscopy in a zoo while the birds were restrained by their keeper (Sivak and Howland 1987). Those birds appeared to be hyperopic (farsighted) by 2 7 D. In this study, examination with infrared photorefraction of the focusing of two unrestrained, feeding birds showed that they could focus objects at infinity and objects in their immediate environment and that they had modest powers of accommodation. Measurements on two 6 month old kiwi chicks showed their corneal radius of curvature to be between 2.90 and 3.00 mm (117 D and 101 D in power). PMID- 1432850 TI - Temporal analysis of adaptation in moth (Trichoplusia ni) pheromone receptor neurons. AB - The temporal pattern of response in chemoreceptor neurons reflects both the temporal distribution of stimuli and the timing of signal transduction, action potential generation and propagation. Here we analyze the temporal characteristics of the responses elicited in pheromone receptor neurons by computer-controlled rectangular pulses of odorant. Extracellular recordings from the HS sensilla trichodea on the antenna of male Trichoplusia ni reveal the activity of two neurons: the "A" neuron, which responds to the major component of the female pheromone blend, (Z)7-dodecenyl acetate and the "B" neuron, which responds to (Z)7-dodecenol. "B" neurons were divided into two classes (HR, LR), based on the magnitude and temporal pattern of their response to (Z)7-dodecenol. Most "A" and HR "B" neurons responded to rectangular pulses of various durations (0.1-40 s) with an initial phasic burst (approximately 100 ms), followed by a slowly declining tonic component. At moderate and elevated pheromone doses, prolonged stimulation resulted in significant reductions in the tonic response levels (adaptation); stimuli of increasing duration effected greater adaptation. Most LR "B" neurons lacked a phasic response component and showed virtually no adaptation with prolonged stimulation. Pheromone receptor neurons may differ in both their spectral and temporal response properties which may provide the animal with additional sensory information for blend discrimination and spatial orientation in complex natural pheromone plumes. The potential functional value of adaptation in the moth pheromone communication system is discussed. PMID- 1432851 TI - Changes in brain amine levels associated with the morphological and behavioural development of the worker honeybee. AB - Changes in biogenic amine levels associated with the morphological and behavioural development of the worker honeybee are examined. A significant increase in amine levels in the head of the honeybee is associated with transition from the larval to pupal stage. Adult emergence is also accompanied by a significant increase in 5-HT levels in the brain, but no significant change in brain dopamine (DA) levels. NADA (N-acetyldopamine) levels increase during larval and pupal development, but in contrast to both DA and 5-HT, drop significantly during the transition from pupa to adult. Levels of DA in the brain of nectar and pollen forager bees, presumed to be among the oldest adults sampled, were found to be significantly higher than in nurses, undertakers or food storers. These results suggest that an age-dependent change in amine levels occurs in the brain of the worker bee. In the optic lobes, levels of DA and 5-HT were found to be significantly higher in pollen forager bees than in all other behavioural groups. Significant differences in amine levels in the optic lobes of nectar foragers and pollen foragers indicate that some differences in amine levels occur independent of worker age. The functional significance of differences in brain amine levels and whether or not biogenic amines play a direct role in the control of honeybee behaviour has yet to be established. PMID- 1432852 TI - Synaptic interactions among neurons that coordinate swimmeret and abdominal movements in the crayfish. AB - 1. Many interneurons in the crayfish (Procambarus clarkii) abdominal nervous system influence two behaviors, abdominal positioning and swimmeret movements. Such neurons are referred to as dual output cells. Other neurons which influence either one behavior or the other are single output cells. 2. Extensive synaptic interactions were observed between both dual and single output neurons involved in the control of abdominal positioning and swimmeret movements. Over 60% of all neuron pairs examined displayed interactions. Pairs of agonist neurons displayed excitatory interactions, while pairs of antagonists had inhibitory interactions. This pattern of interaction was observed in about 75% of interactive neuron pairs whether abdominal positioning or swimmeret outputs were considered. 3. Evidence for both serial and parallel connectivity, as well as, reciprocal or looping connections was observed. Looping connections can be found both between the abdominal positioning and swimmeret systems and within each system. 4. Most (28/34) single output neurons were not presynaptic to dual output neurons. No single output neurons were found to excite dual output neurons to spiking, although inhibitory interactions and weak excitations were observed. 5. Abdominal positioning inhibitors displayed properties consistent with a role in mediating some of the coordination between the swimmeret and abdominal positioning systems. 6. None of the dual output neurons examined influenced the swimmeret motoneurons directly. PMID- 1432853 TI - Characteristics of dynamic postural reactions in the locust hindleg. AB - The use of the locust (Schistocerca americana) hindleg in postural control was examined in animals that stood on a repeatedly swayed vertical substrate. Myograms were recorded from leg muscles and the angle of the femoro-tibial joint was monitored photographically. Two discrete strategies were observed; in compensatory reactions the hindleg was held in place, while in "flexion" reactions, the leg was moved, most often to complete flexion of the femoro-tibial joint. Tightly coupled, rhythmic bursting occurred in the flexor and levator muscles of the leg during compensatory reactions. Bursting was initiated repeatedly when the substrate was being pulled away from the animal. Bursting was correlated with subsequent decreases in the rate of change of the femoro-tibial joint angle. Compensatory and "flexion" reactions occurred preferentially in different ranges of joint angles: most often, compensatory reactions occurred in the mid-range, while "flexion" reactions were elicited in the extremes of joint angle. These differences may be due to the mechanical advantages of the tibial muscles and the leg may be moved to full flexion because of a locking mechanism of the flexor muscle tendon. These reactions are compared with known reflexes of hindleg proprioceptors and contrasted with similar responses of vertebrates. PMID- 1432854 TI - Motion analysis of leg joints associated with escape turns of the cockroach, Periplaneta americana. AB - Considerable information is now available on the neural organization of the escape system of the American cockroach. To relate these data to the behavior, we need detailed information on the movements made at the principle leg joints that produce the turn. We used motion analysis of high speed video records to acquire such information. Records from both free ranging and tethered animals were analyzed. 1. We analyzed individual joint movements using a tethered preparation. Stimuli from 4 different angles around the animal were used. For all wind angles, the femur-tibia (FT) joint on the mesothoracic leg that is ipsilateral to the wind source extended while the contralateral mesothoracic FT joint flexed. This moved both of these legs laterally toward the wind source. In freely moving animals the FT movements provide forces that turn the animal away from the wind source. 2. The ipsilateral mesothoracic coxa-femur (CF) joint extended for all wind angles. The contralateral mesothoracic CF joint extended in response to most winds from the rear, but switched to flexion in response to wind from the side and front. As a result of these joint movements, rear wind resulted in rearward movements of the contralateral mesothoracic leg, while side and front wind resulted in more forward movements of that leg. 3. The CF and FT joints for both ipsilateral and contralateral metathoracic legs extended to wind from the rear and switched to flexion as the wind was placed at more anterior positions around the animal. In freely moving animals, extension of these joints would push the animal forward. Flexion would pull the animal backward. 4. Several of the joints showed correlations between rate of movement and initial joint angle. That is, joints that were already flexed at the onset of stimulation tended to move at a faster rate to a final position than joints that started at a more extended position. 5. Metathoracic FT and CF joints showed a high degree of positive correlation during the escape movements. Indeed, many curves showing movement of metathoracic FT and CF joints with time were virtually identical. PMID- 1432855 TI - Intersegmental interneurons serving larval and pupal mechanosensory reflexes in the moth Manduca sexta. AB - 1. Intersegmental interneurons (INs) that participate in the larval bending reflex and the pupal gin trap closure reflex were identified in the isolated ventral nerve cord of Manduca sexta. INs 305, 504, and 703 show qualitatively different responses in the pupa than in the larva to electrical stimulation of sensory neurons that are retained during the larval-pupal transition to serve both reflexes. Action potentials produced by current injected into the 3 interneurons excite motor neurons that are directly involved in the larval and pupal reflexes. The excitation of the motor neurons is not associated with EPSPs at a fixed latency following action potentials in the interneurons, and thus there do not seem to be direct synaptic connections between the interneurons and the motor neurons. 2. IN 305 (Fig. 2) has a lateral soma, processes in most of the dorsal neuropil ipsilateral to the soma, and a crossing neurite that gives rise to a single contralateral descending axon. IN 305 is excited by stimulation of the sensory nerve ipsilateral to its soma in the larva and the pupa. Stimulation of the sensory nerve contralateral to its soma produces an inhibitory response in the larva, but a mixed excitatory/inhibitory response to the identical stimulus in the pupa. 3. IN 504 (Fig. 3) has a lateral soma, processes throughout most of the neuropil ipsilateral to the soma, and a crossing neurite that bifurcates to give rise to a process extending to the caudal limit of the neuropil and an ascending axon. IN 504 is excited by stimulation of the sensory nerve ipsilateral to its soma in both larvae and pupae, while the response to stimulation of the sensory nerve contralateral to its soma is inhibitory in the larva but mixed (excitatory/inhibitory) in the pupa. 4. IN 703 has a large antero lateral soma, a neurite that extends across to the contralateral side giving rise to processes located primarily dorsally in both ipsilateral and contralateral neuropils, and two axons that ascend and descend in the connectives contralateral to the soma (Fig. 4). IN 703 responds to stimulation of the sensory nerves on either side of the ganglion, but the form of the response changes during the larval-pupal transition. In the larva, the response consists of very phasic (0-2 spikes) excitation, but in the pupa there is a prolonged excitation that greatly outlasts the stimulus (Fig. 6).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432856 TI - Xenopus exhibits seasonal variation in retinotectal latency but not tecto-isthmo tectal latency. AB - 1. The tectum of Xenopus receives visuotopic input from both eyes. The contralateral eye's projection reaches the tectum directly, via the optic nerve. The ipsilateral eye's projection reaches the tectum indirectly, via the nucleus isthmi and isthmo-tectal projection. 2. Because of the multi-synaptic nature of the ipsilateral pathway, there is an inherent delay between the time that information from the contralateral eye reaches the tectum and the time that information from the ipsilateral eye arrives at the tectum. The length of the intertectal delay is a function of the latencies of the contralateral and ipsilateral pathways. 3. The length of this intertectal delay has functional, as well as developmental, implications with regard to the role of N-methyl-D aspartate receptors in tectal cell activity and development of orderly synaptic connections. 4. We have found that the latencies of the contralateral and ipsilateral pathways exhibit a seasonal variation, increasing during the winter months. The increases of both latencies during the winter were of similar magnitude, indicating that there were no significant changes in intertectal delay. The seasonal alteration in contralateral latency was not affected by dark rearing and was affected to only a minor extent by a week-long alteration of ambient temperature. PMID- 1432857 TI - Interneurons of the subesophageal ganglion of Sarcophaga bullata responding to gustatory and mechanosensory stimuli. AB - Intracellular recordings were made from interneurons in the subesophageal ganglion (SEG) of Sarcophaga bullata while stimulating the labellar lobes with solutions of sucrose, NaCl and with distilled water. Neurons that responded to sucrose did not respond to NaCl and vice versa, while sucrose-sensitive neurons often responded weakly to water. Several of the recorded neurons were filled with Lucifer Yellow, and their morphology was reconstructed. Most showed extensive arborizations within the SEG, suggesting that they were local interneurons involved in the early stages of gustatory processing. Some of the filled neurons had extensive projections to the brain, in addition to arborizations in the SEG. This is the first published record of gustatory interneurons in the higher flies. PMID- 1432858 TI - Midbrain auditory sensitivity in the spring peeper (Pseudacris crucifer): correlations with behavioral studies. AB - 1. We derived audiograms from recordings of multiunit activity in the torus semicircularis of 10 males and 6 females of the spring peeper from central Missouri, USA. We used free-field stimulation with tone bursts that had temporal properties similar to typical advertisement calls and that ranged in frequency from 500-6000 Hz. 2. Audiograms from different electrode positions in the same animal had the same general shape. There was no evidence of tonotopy. 3. Audiograms showed two regions of maximal sensitivity: a low-frequency region (500 700 Hz); and a high-frequency region (2000-4000 Hz). Absolute thresholds and frequencies of maximum sensitivity varied considerably from individual to individual. 4. Audiograms derived from all individuals of each sex indicated that in the high-frequency region, corresponding to the frequency range of advertisement calls, males were more broadly tuned than females. However, tuning in both sexes was relatively weak, and the data predict relatively little selectivity in behavioral responses over the entire range of variation in frequency of the advertisement call in local populations. 5. The results are discussed in terms of behavioral experiments with both males and females from the same populations in central Missouri. We show that merely summarizing the audiograms based on estimates of minimum thresholds of a population or species may mask significant individual differences in tuning. Moreover, most behavioral studies are conducted at playback levels considerably above threshold. For these reasons, behavioral selectivity is not always accurately predicted by inspection of "average" audiograms. PMID- 1432859 TI - Does reactivity testing in the laboratory reflect blood pressure changes elsewhere? AB - This study examines whether reactivity testing in a laboratory setting might identify individuals whose blood pressure (BP) fluctuates excessively outside of the laboratory. Eighty-eight normotensive and untreated hypertensive patients were studied. Patients' BPs were obtained repeatedly on two separate screening occasions. They were subsequently admitted to a research ward, and 4 days later their BPs were measured at resting baseline and in response to a series of stressful tasks. Blood pressure declined by 14/11 mm Hg +/- 1.2/1.1 mm Hg (SE) from screening to the in-patient resting baseline. The four stressful tasks all led to increases in BP over the in-patient resting baseline level. Individuals with increased amounts of task-induced reactivity in the laboratory were also more likely to be those whose BP declined the most from out-patient screening to hospitalized baseline. The average correlation between the drop in BP associated with hospitalization and the BP reactivity to each stressor task was r = 0.33 for systolic BP (p < 0.01) and r = 0.24 for diastolic BP (p < 0.05). Reactivity responses in a laboratory setting may convey information about blood pressure fluctuation in the real world. PMID- 1432860 TI - Negative affect and the experience of chronic pain. AB - Although it is clear from previous research that pain is associated with negative affect, the relative contribution of specific affective dimensions, e.g. depression, anxiety and anger, to the subjective experience of chronic pain is unclear. The literature is also mixed concerning the relative importance of state versus trait influences in the experience of chronic pain. The present study analyzed the ability of anxiety, anger, and depression (as measured by the State Trait Personality Inventory, State-Trait Anger Expression Inventory, and the Beck Depression Inventory, respectively) to predict self-report of clinical pain as indicated by the McGill Pain Questionnaire (MPQ) in a sample of 60 chronic pain patients. The results of stepwise regression analyses consistently demonstrated that the state measures were more strongly related to MPQ pain ratings than trait measures. These data suggest support for the hypothesis that chronic pain adversely impacts mood rather than the opposing hypothesis that negative mood is a predisposing factor in the development of chronic pain. Furthermore, different aspects of the state emotional experience were found to be related to different components of pain report. The results of this study also suggest that attributional processes could be an important component of the relationship between negative mood and the experience of pain. PMID- 1432861 TI - Psychological factors in patients with non-specific abdominal pain acutely admitted to a general surgical ward. AB - Non-specific abdominal pain is the commonest reason for acute admission to a general surgical ward. The present study assessed the importance of specific symptom patterns, psychological and behavioural factors in a group of acute admissions and compared patients with appendicitis with those with no specific diagnosis. Psychiatric symptoms were no more prominent than in subjects with appendicitis as measured by psychological rating scales. Patients with non specific abdominal pain had a poor symptomatic prognosis with continuing use of medical services. NSAP is best seen as a behavioural syndrome with repeated consultation over a long period before and after the index admission for both abdominal and other non specific symptoms. PMID- 1432862 TI - Factors which provoke post-infarction depression: results from the post infarction late potential study (PILP). AB - Symptoms of depression in the majority of patients immediately following acute myocardial infarctions (AMI) resolve rapidly; they are an adjustment reaction. However, in a group of 552 male patients there were 80 (14.5%) patients with persistent major depressive symptoms during a finite period after AMI. Infarction size was assessed by maximum creatine kinase levels, the QRS-complex and the occurrence of late potentials. These measures did not correlate with the degree of depressed moods in these groups. An arrhythmic event in the early hospitalization phase, a recurrent infarction, dyspnoea, and persistent angina pectoris before the AMI were significantly related to more profound degrees of depression. Patients who reported serious life-events in the last 2 yr before AMI, or who suffered from exhaustion and fatigue in the prehospital phase were subject to significantly higher levels of depression. A prodromal phase prior to hospitalization free of bodily symptoms and the use of denial were related to low levels of depression. The logistic regression model incorporating all univariate significant variables revealed that symptoms of exhaustion and fatigue prior to AMI had the strongest independent correlation with post AMI depression. PMID- 1432864 TI - Childhood asthma: paternal critical attitude and father-child interaction. AB - The study investigated paternal critical attitude (CA) and negative father-child communication in families with an asthmatic child and in controls. Twenty-seven children with bronchial asthma (6-13 yr) and 23 healthy children with their fathers participated in the project. Fathers were asked to describe their child (Five Minute Speech Sample; FMSS). Additionally, father and child discussed a mutual problem (Problem Discussion; PD). Tape recordings were taken. Critical attitude (CA) was assessed from the fathers' responses during the FMSS. Negative verbal behavior during PD was coded for father and child. During the FMSS, significantly more fathers of the asthmatic children than of the controls showed CA. During the PD, fathers of the asthmatic children made significantly more critical remarks than their controls. Significantly more long sequences of negative verbal communication occurred in father-child dyads with an asthmatic child than in the control dyads. No significant relationship was found between either the fathers' attitudes or amount of negative verbal communication and the children's severity of asthma, compliance, or IgE status. PMID- 1432863 TI - Symptoms, anxiety and handicap in dizzy patients: development of the vertigo symptom scale. AB - Questionnaires assessing symptoms, anxiety and handicap were completed by 127 vertiginous patients. Factor analysis identified four distinct symptom clusters which formed the basis for the construction of scales quantifying the number and frequency of symptoms of: (a) vertigo (of long and short duration); (b) autonomic sensations and anxiety arousal; and (c) somatization. Scores on the vertigo severity scale were significantly related to clinical diagnosis and had near-zero correlations with measures of anxiety. Vertigo severity, autonomic signs and depressed mood each independently contributed to variance in handicap, taking precedence over the relationship between handicap and trait and state anxiety. Our findings suggest that the familiar association between anxiety and vertigo may be mediated principally by autonomic symptomatology arising as a result of somatopsychic and psychosomatic processes. PMID- 1432865 TI - The outcome of unexplained dyspepsia. A questionnaire follow-up study of patients after endoscopy. AB - Ninety-three consecutive patients referred to a gastroenterology unit with unexplained dyspeptic symptoms were sent a postal questionnaire 6-12 months after endoscopy. It inquired into their current physical symptoms and subjective improvement since investigation, satisfaction with treatment, past history and current psychological well-being. A comparison group of 47 patients with peptic disease were similarly surveyed. Those with unexplained dyspepsia reported more current physical symptoms, more dissatisfaction with their treatment and less subjective improvement than those with peptic disease. The two groups were similar in terms of psychological distress but previous consultation for abdominal and other somatic complaints were more common in those with unexplained dyspepsia. The implications for management of dyspeptic patients are discussed. PMID- 1432866 TI - Helping parents and children with epilepsy cope successfully: the outcome of a group programme for parents. AB - This paper describes a study to determine the effectiveness of a group programme for parents designed to reduce the psychosocial morbidity among children with epilepsy and their families. The participants were the parents of 108 children attending the seizure clinic at a children's hospital. The first part of the project had shown that half of the children and their families had considerable morbidity. Despite the high rate of psychosocial morbidity among these children and their families, only 35% of the parents expressed an interest in participation in the intervention programme, with only 12% attending any meetings. The latter were mainly the small number of parents whose children had severe intractable epilepsy as well as educational and family problems. Many parents did, however, request more information about epilepsy and for the provision of a counselling service. The latter is likely to be most beneficial in the months following diagnosis. PMID- 1432867 TI - The effects of suggestion on airways of asthmatic subjects breathing room air as a suggested bronchoconstrictor and bronchodilator. AB - Thirty-three asthmatic subjects were told they were receiving, alternately, an inhaled bronchoconstrictor and inhaled bronchodilator, although they actually were only breathing room air. No subjects showed suggestion-produced effects on FEV1, although two (of the 19 on whom FEF50 was measured) showed effects of greater than 20% on measures of maximal midexpiratory flow. The incidence of the effect is smaller than reported previously, possibly because some subjects in previous studies inhaled saline, a mild bronchoconstrictor, and reversal of effect was not required for classification as a reactor. Higher percentages of subjects in this study showed decreased MMEF in response to the 'bronchoconstrictor', but this appeared to reflect fatigue rather than suggestion effects. However, the fact that the effect occurred in a relatively non-effort dependent measure suggests that real changes occurred in bronchial caliber, not just in test effort. Suggestion had a significant effect on perception of bronchial changes, but the correlation between actual and perceived changes was minimal. There was an increase in FVC prior to administration of the 'bronchoconstrictor', possibly reflecting a preparatory response to the expected drug. Correlations among self-report variables suggested the existence of three personality dimensions among our population related to suggestion and asthma: cognitive susceptibility to suggestion of bronchial change; feeling of physical vulnerability; and anxiety. However, there was no significant relationship between airway response to suggested changes and hypnotic susceptibility, as measured by the Harvard Group Scale of Hypnotic Susceptibility. PMID- 1432868 TI - Exhaustion, psychological stressors in the work environment, and acute myocardial infarction in adult men. AB - In a case-control study in adult men from The Netherlands, the associations of work stressors with both exhaustion prior to first acute myocardial infarction (AMI) and with first AMI itself were explored. The 133 AMI-cases reported more exhaustion, work stressors, and smoking than the controls (i.e. 133 neighborhood controls and 192 hospital controls). After controlling for smoking, exhaustion constituted a firm risk indicator for first AMI; it was also positively associated with work stressors, in particular conflicts at work. Work stressors that may disrupt one's occupational career, and increased responsibility (in younger AMI-cases), were directly associated with elevated risk for first AMI. Conflicts at work were conducive to first AMI through their associations with exhaustion. PMID- 1432869 TI - Perception of family and work environments in women with premenstrual syndrome. AB - Seventy-three women with a prospectively confirmed diagnosis of Premenstrual Syndrome (PMS) were compared to 50 routine gynaecological care non-PMS controls on measures of social climate/environmental stress. Tests administered included the Family Environment Scale (FES), Work Environment Scale (WES), Spielberger State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI). The PMS group scored significantly higher on amount of conflict in their families as well as on emphasis on ethical and religious values but lower on direct emotional expressiveness within the family, intellectual-cultural orientation, and active-recreational orientation as compared to controls. Furthermore, the PMS group perceived having more work pressure, less autonomy on the job, and less variety in their work than controls. Overall, psychological distress was not associated with increased environmental stress either in the PMS or control groups. PMID- 1432870 TI - Courses for horses. PMID- 1432871 TI - Black looks ... at 'isms'. PMID- 1432873 TI - Smoking: its influence on survival and cause of death. AB - Smoking is strongly associated with age-specific death rates for a number of diseases. Increased age-specific death rates for a disease may imply either more deaths from the disease with increased absolute lifetime risk, or earlier deaths, without increased absolute lifetime risk. The British doctor smoking data are re analysed using lifetable methods for survival, cumulative mortality and the disease-specific cumulative mortality. The most significant effect of smoking is on survival: life shortening amounts to three years for light smokers, five for moderate smokers, and eight for heavy smokers, compared with those who never smoked. Smoking increases the absolute number of deaths from some causes, including lung cancer; for other causes, including ischaemic heart disease, it brings forward death without increasing the absolute number of deaths. The smoking associations with more or earlier death have implications for research into the mechanisms of disease causation, for health promotion, for rational health-care planning, and for social policy. PMID- 1432872 TI - Smoking and the young. Summary of a report of a working party of the Royal College of Physicians. PMID- 1432874 TI - Twenty-four-hour blood pressure in junior medical staff. AB - Circadian variations in blood pressure in junior medical staff were compared during routine working days and days receiving medical emergencies. The overnight work commitment of junior medical staff when receiving medical emergencies causes a loss in the normal circadian blood pressure rhythm, with overnight blood pressure falling 10/11 mmHg less than on routine working days. This supports the hypothesis that circadian blood-pressure changes are activity related rather than dependent upon hormonal variation. Long-term health effects of abolishing such normal circadian rhythms are not known. PMID- 1432875 TI - Instructors--a weak link in resuscitation training. AB - One explanation for the well documented poor basic resuscitation skills of health care professionals is that these skills are not acquired during initial training. The first aim of our study was to assess the basic life-support skills of trainers teaching basic resuscitation. The second aim was to examine the relationship between the trainers' confidence and actual skill. We found that practical basic life-support skills prior to the two-day training course were poor. They were still inadequate after training. Assessments before and after the course showed significant positive correlation between confidence at performing basic life-support and actual skill. There is an urgent need for formal instructor training in the UK. The training programme should be evaluated, as should the performance of both trainers and trainees, to ensure that all have acquired the requisite skills. PMID- 1432876 TI - Do cytokines play a role in systemic lupus erythematosus? AB - Excessive production of pathogenic autoantibodies is one of the hallmarks of systemic lupus erythematosus (SLE). The mechanisms that underlie this excessive production are still unclear. Although there is considerable evidence to suggest that both T-cells and B-cells play an important role in the aetiology of SLE, convincing abnormalities at the T-cell receptor or immunoglobulin gene loci have not been demonstrated. In this regard, because cytokines play a pivotal role in the inflammatory response, a defect in the immunoregulation of B-cells by cytokines should be considered as a potential contender in disease aetiology. The hypothesis proposed here is that multiple cytokine-mediated defects are present in individuals with lupus and that both cytokine production and the response of B cells to cytokines may be defective. PMID- 1432877 TI - Resuscitation status of the elderly. AB - Resuscitation of patients in hospital following cardiopulmonary arrest is a standard procedure. Such intervention is not always appropriate, and this article examines some of the issues involved in making the decision not to resuscitate, with particular reference to elderly patients. The effectiveness and possible adverse effects of cardiopulmonary resuscitation (CPR) in the elderly are considered, along with ethical aspects of the problem such as how to discuss the pros and cons with the patient and relatives. PMID- 1432878 TI - The MD thesis in the training of a consultant physician. AB - A postal survey was carried out among the 94 consultant physicians of the South Western region (83% response rate) to ascertain their attitudes to the tradition of obtaining an MD by thesis as part of a physician's training. Most felt that the practice was questionable, and only half felt that it made an important contribution. For some, doing an MD had been a painful experience, even a waste of time. Having an MD impressed selection committees, but did not appear to alter the length of training nor the probability of obtaining a consultant post in a teaching hospital. We suggest that the MD is of limited value in judging a junior doctor's suitability to be a consultant physician. PMID- 1432879 TI - Formal appraisal of junior medical staff. PMID- 1432880 TI - Generic substitution--another form of alternative medicine. PMID- 1432881 TI - Choices in health care. A review of a report by the government Committee on Choices in Health Care. Ministry of Welfare, Health and Cultural Affairs, The Netherlands, 1992. PMID- 1432882 TI - Health in the Czech Republic. PMID- 1432884 TI - Decision logic in medical practice. The Milroy Lecture 1992. PMID- 1432883 TI - Vitamin D metabolism in renal disease. Sir Michael Perrin Lecture 1991. PMID- 1432885 TI - Rehabilitation of the elderly in the 21st century. The F. E. Williams Lecture 1992. PMID- 1432887 TI - The Hong Kong Academy of Medicine. AB - The Hong Kong Academy of Medicine is being founded this year. This brief article gives something of the background, structure and function of the Academy. PMID- 1432886 TI - Genetics in the reformed health service. Changes for the better? AB - The practical value of medical genetics, in particular the development of molecular genetics complemented by clinical diagnosis and counselling, is widely recognised. There is strong independent support from government and patient organisations for augmenting genetics services in all health regions; this support gives much reason for optimism. But there appears to be a hiatus following the reform of the Health Service: no genetics centre has, as yet, adequate resources and there has been no increase in clinical genetic manpower in the last two years. Even worse, Wales and at least one English region have devolved genetic services to districts, which appears to be contrary to government policy for genetic services. These factors have inevitably limited the implementation of many opportunities for improved patient care and the prevention of genetic disease. However, medical geneticists, assisted by the Royal College of Physicians and others, want to respond positively to the changes in the Health Service. Recommendations are made for strategies which promise to maintain integrated regional clinical and laboratory services and to achieve well evaluated developments. PMID- 1432888 TI - Per capita payments for clinical trials. PMID- 1432889 TI - In pursuit of a dubious principle. PMID- 1432890 TI - So, what is a clinical oncologist? PMID- 1432891 TI - So, what is a clinical oncologist? PMID- 1432892 TI - So, what is a clinical oncologist? PMID- 1432893 TI - Diagonal earlobe creases. PMID- 1432894 TI - Management of GI haemorrhage. PMID- 1432895 TI - GI bleeding and rheumatologists. PMID- 1432896 TI - Management of upper gastrointestinal haemorrhage. PMID- 1432897 TI - Who's for CPR? PMID- 1432899 TI - The Brown Kelly-Paterson not Plummer-Vinson syndrome. PMID- 1432898 TI - Completing 'interim discharge letter'. PMID- 1432900 TI - Anemia of chronic renal failure in dogs. AB - Seventeen dogs with chronic renal failure (CRF) were studied to evaluate the incidence, type, and etiology of anemia in CRF. A nonregenerative, normochromic, normocytic anemia was seen in 12 of 17 dogs (70.6%). There was a direct correlation between the degree of anemia and the extent of CRF as assessed by serum creatinine concentrations (P = .0386, r = .50923). Erythrocyte concentrations of 2,3-diphosphoglycerate (DPG) were significantly increased in anemic animals and showed a close correlation to the degree of anemia. The high DPG concentrations may compensate for the anemia by decreasing the hemoglobin oxygen affinity and thereby facilitating tissue oxygenation at low hematocrits. Serum concentrations of erythropoietin (Epo) were in the low to normal range, despite mild to moderate anemia, documenting a deficiency of Epo in dogs with CRF. The nonregenerative nature of the anemia supports impaired hematopoiesis as a significant etiologic factor. Other factors, such as increases in serum parathyroid hormone and phosphorus, were not found to correlate significantly with the degree of anemia, although there were significant differences between their concentrations in anemic compared with non-anemic dogs. There was no change in erythrocyte osmotic fragility with uremia. The documentation of a nonregenerative, normochromic, normocytic anemia, with failure of an appropriate increase in Epo production, supports the therapeutic use of Epo in the management of the anemia seen in CRF in the dog. PMID- 1432901 TI - Hematologic toxicosis associated with doxorubicin administration in cats. AB - The hematologic toxicity of doxorubicin, 30 mg/m2 body surface area (BSA) every 21 days to a cumulative dose of 300 mg/m2, was evaluated in six cats. Complete blood and platelet counts were performed daily during the first treatment cycle. They were monitored before treatment for all remaining cycles, and at the average neutrophil nadir (day 8) starting with cycle 4. Significant poikilocytosis developed after the first treatment and remained throughout the study, although anemia did not occur. No other red blood cell abnormalities were seen. Platelet counts remained within the reference range throughout the first treatment cycle, but mild thrombocytopenia (88,000-288,000/uL) was found in 11.3% of subsequent complete blood counts (CBCs). Thrombocytosis was seen in 30.9% of CBCs. Neutropenia did not occur during the first treatment cycle although neutrophil counts did decrease, with the nadir occurring between days 8 and 11. All neutrophil counts returned to pretreatment values by day 14. Neutropenia was documented after 14 of 46 (30.4%) doxorubicin treatments, and was associated with fever in 5 cats (10.9%). All fevers responded to oral antibiotic therapy. Neutropenia that lasted more than 14 days developed in two cats, necessitating dosage reduction to 25 mg/m2 BSA. At the dose used in this study, doxorubicin administration was associated with acceptable hematologic toxicosis in most cats. PMID- 1432902 TI - Lymphedema. Etiopathogenesis. PMID- 1432903 TI - Hyperkalemic atrial standstill in neonatal calf diarrhea. AB - Hyperkalemia has been associated with cardiac abnormalities and muscular disorders. Hyperkalemia is a common problem associated with the acid-base and electrolyte disturbances that occur in neonatal calves having acute diarrhea. Occasional calves with acute neonatal diarrhea, metabolic acidosis, and hyperkalemia have cardiac rate or rhythm abnormalities. Bradycardia observed in three such calves was found to represent atrial standstill and was attributed to hyperkalemia. PMID- 1432904 TI - Specialty of oncology certifying examination. PMID- 1432905 TI - Single-drug chemotherapy of canine transmissible venereal tumor with cyclophosphamide, methotrexate, or vincristine. PMID- 1432906 TI - Low presented 1992 Kirk Award. PMID- 1432907 TI - [High-resolution MRI of the carpal tunnel. Anatomical correlations]. AB - This anatomical study of the carpal tunnel compares magnetic resonance imaging sections and adult and fetal anatomical sections. The MRI studies were carried out in 12 normal controls. The use of an experimental high resolution module allows achieving as high a degree of spatial resolution as 0.13 mm2. The comparison of MR images with anatomical sections allows a very accurate analysis of the contents of the carpal tunnel, especially of the median nerve, of the flexor tendons and of the flexor retinaculum. PMID- 1432908 TI - [Evaluation of osteodensitometry. Report of the National Agency for the Development of Medical Evaluation]. AB - The progress made in recent years in the field of bone densitometry, particularly concerning dual-energy x-ray absorptiometry, has resulted in the development of reliable techniques of bone mineral density measurement, especially for measurements in the lumbar spine on anteroposterior views and in the forearm. However, technical improvements are still necessary and concern the standardisation of equipment, measurements in the femur, on lateral views of the lumbar spine and on the whole body, and the definition of normal curves. The value of these measurements must be examined in the light of the epidemiological context of osteoporosis and its current and future cost to the community. They must be evaluated in relation to two pathological situations: osteoporosis and osteopenia. Osteoporosis is a disease characterised by the development of fractures due to bone fragility. It is accompanied by a reduction in bone density and other abnormalities of bone architecture and metabolism, without any disturbance of mineralisation. It is responsible for pain, a functional handicap which alters the patient's quality of life. Osteopenia corresponds to an abnormally low bone density. It is accompanied by an increased risk of fractures. Although it remains asymptomatic, therapeutic intervention may nevertheless be justified. The threshold of therapeutic intervention depends on the degree of bone loss, the patient's age, other associated risk factors and the benefit-risk ratio of the drug used. In all forms of vertebral osteoporosis, the essential conditions for the diagnosis are a decreased vertebral bone density and deformation of a vertebral body.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432909 TI - [X-ray computed tomography of the facial sinuses. Results in 198 patients with chronic sinusitis]. AB - The CT studies of 198 consecutive patients with chronic sinusitis were reviewed retrospectively. CT was normal in 47 patients (23.7%). In 151 patients one or many cavities showed abnormalities. In 69 cases (34.9%), the lesions affected one or two sinuses, in 35 cases (17.7%) three to six cavities were abnormal, whereas in 47 cases (23.7%), more than six cavities were abnormal. In 87 cases (57.6%), lesions were observed both in large cavities and ethmoid cells, whereas they were selectively localized in large cavities in 55 cases (36.4%), or in ethmoid cells in 9 cases (6%). Abnormalities were observed in the maxillary sinus in 137 patients (69.2%), in the ethmoid in 96 patients (48.5%), in the frontal sinus in 51 patients (25.8%), and in the sphenoid sinus in 28 patients (14.1%). The most frequent abnormality was hypertrophic mucosa, which was visible in 275 cavities. These results were compared with date of the literature. PMID- 1432910 TI - [Latero-cervical septate cystic lesions in adults]. AB - Laterocervical septated lesions are infrequent in adults, and their etiological diagnosis is difficult. The authors report about four cases in which an exploration with imaging and an anatomical control were performed. Two etiologies are specially interesting, either because of their remarkable features with imaging (cystic lymphangioma) or because they require formal identification (metastatic adenopathy from thyroid or ovarian papillary carcinomas). While modern imaging can confirm the diagnosis, and sometimes define the treatment (cystic lymphangioma), the surgical exeresis of such lesions remains imperative in all cases of atypical appearances, in order to avoid leaving a prevailing lymph node metastasis unrecognized. PMID- 1432911 TI - [Extrapleural hematoma]. AB - The authors report a case of a voluminous extra-pleural hematoma in relation to a fracture of the body of the eleventh thoracic vertebra on a 74 year-old man after craniothoracic injury. Thoracic CT Scan showed a homogeneous posterior parietal mass of tissue density (40 HU) outlined by a fatty lining associated with a fracture of the eleventh thoracic vertebra. This allowed a modification in the diagnosis of a hemothorax established previously on conventional radiography. The authors insist on the gravity of this affection when the volume of the hematoma is important. But this is very rare (6 cases out of which 5 were autopsic findings). If present it requise an urgent surgical treatment without forgetting the fiability of CT Scan which relies on putting into evidence the pleural lining sign. PMID- 1432912 TI - [Sezary syndrome with rapidly progressing pulmonary lymphoma in a child]. AB - A 7 year old boy with a prior history of T-cell acute lymphoblastic leukemia developed Sezary syndrome or cutaneous lymphoma of T-lymphocytes (CLTL). His course was rapidly progressive and fatal with the primary manifestation being pulmonary lymphoma. This patient is one of the youngest with CLTL to manifest extracutaneous involvement. PMID- 1432913 TI - Color velocity imaging. PMID- 1432914 TI - [Overview of radiology in Romania]. PMID- 1432915 TI - [Liability in imaging. The practice of a test with a diagnostic purpose]. PMID- 1432916 TI - Dentists, drugs, and decisions: introduction to Part I--Therapeutic drugs. AB - Numerous dental therapeutic agents or drugs are available over the counter or with prescription for patient use at home or in a professional office. Knowledge of the processes by which these agents are evaluated for safety and efficacy by the FDA and ADA is necessary for dental professionals to make intelligent decisions concerning their use. Several examples of problems with drug/cosmetic evaluations are cited. PMID- 1432917 TI - FDA regulation of OTC oral health care drug products. AB - The history of the involvement of the Food and Drug Administration in the regulation of over-the-counter (OTC) drugs is reviewed. The development of monographs containing standards for drugs, the function of the advisory panels, and the classification of dental drug products are explained. Examples of ingredients in each category are given. The current opinion of the FDA concerning antiplaque and antigingivitis claims is also discussed. PMID- 1432918 TI - FDA's new drug evaluation process: a general overview. AB - A general overview of the FDA new-drug evaluation process is presented with special emphasis on the regulatory requirements as outlined in the federal Food, Drug, and Cosmetic Act and the interpretive New Drug Regulations. Included is a description of the administrative/scientific makeup and functions of the new-drug evaluation divisions within the Center for Drug Evaluation and Research. Some specifics relating to the investigative development of anticaries and plaque/gingivitis new drug products are discussed. PMID- 1432919 TI - The how and why of the ADA's evaluation program for dental therapeutic products. AB - Since 1930, the Council on Dental Therapeutics of the American Dental Association has been evaluating dental drug products for safety and efficacy through its Acceptance Program. To date, numerous products have been evaluated, and many hundreds have received the council's seal of acceptance. Acceptance criteria are rigorous, and the council relies on expert consultants to evaluate the supporting data. There are no manufacturer fees involved with the Acceptance Program. When a product has been awarded the seal, it means that adequate data have been submitted, and that the product is safe and does what it says it will do. This paper describes, in detail, how the Acceptance Program works. PMID- 1432920 TI - ADA dental product evaluation: case history. AB - The ADA Acceptance Programs entail a rigorous evaluation of products and offer clear benefits to manufacturers, dental professionals, and consumers alike. This paper outlines the implications of the ADA product-evaluation programs for each of these three constituencies and concludes that while there may be an occasional downside from the manufacturer's standpoint, their net effect is to provide assurances that products are safe, efficacious, and promoted properly. PMID- 1432921 TI - Professionally applied and prescribed fluoride products. AB - The US regulatory process relative to the marketing of sodium fluoride dietary supplements and professionally applied topical fluorides is examined with regard to interactions of ADA, NIH, academia, and the FDA, as well as resultant effects on industry, practitioners, and patients. Restrictions on noncaries use of fluoride limit commercial claims, but not professional practice. Prenatal fluoride supplements are still unapproved. Finally, the effects of generic competition and the regulatory process on costs, sales, quality of professional fluoride products and on new product research are discussed. PMID- 1432922 TI - How the FDA and the ADA affect development of prescription drugs for oral care. AB - The patient-consumer, the health professional, and the producer are all essential in the world of prescription drugs for oral care. Also essential are the Food and Drug Administration (FDA) and the American Dental Association (ADA). The FDA is charged with reviewing new-drug applications in the United States and approving those drugs that are proved safe and effective. The FDA also controls prescription-drug advertising and promotion. The ADA applies professional standards in judging all submitted dental drugs. Those drugs accepted by ADA's Council on Dental Therapeutics may display the ADA seal in labeling and advertising. All advertising for accepted products must be cleared by the ADA. An example of a prescription drug approved by the FDA and accepted by the ADA is 0.12 percent chlorhexidine gluconate oral rinse (Peridex). This drug followed the FDA's investigational-drug (IND) regulations before final approval as a treatment for gingivitis. PMID- 1432923 TI - Statistical vs clinical significance in product testing: can they be designed to satisfy equivalence? AB - Statistical issues associated with demonstrating significance between treatment groups (efficacy or superiority) and nonsignificance (equivalence) are presented and discussed. Methodologies for demonstrating efficacy of a product are proposed and contrasted, incorporating clinical and statistical criteria, with emphasis on situations in which placebo groups are precluded from the study design. Distinctions are drawn between study designs for demonstrating superiority and those for equivalence, including the determination of sample sizes needed for the different approaches. The "at least as good as" criterion is proposed as a reasonable alternative to that of equivalence in active control equivalence studies for demonstrating that dental product modifications or new products are efficacious. PMID- 1432924 TI - Dentists' uncertainties about materials and devices: an introduction to the problem. AB - Questions concerning evaluation of dental materials and devices by the FDA and ADA are raised. Examples of several products are discussed. PMID- 1432925 TI - FDA regulation of dental devices: past, present, and future. AB - The organization of the Food and Drug Administration as related to dental devices is described. The classification according to safety and efficacy of devices is described and examples are given. The process of submitting a Premarket Notification [(510(k)] for class I and II devices, a Premarket Approval (PMA) for class III devices and an Investigational Device Exemption (IDE) are described. The clinician is told how to report problems with medical devices. PMID- 1432926 TI - The how and why of the ADA's evaluation of dental materials, instruments, and equipment. PMID- 1432928 TI - FDA and ADA evaluation of dental implants. AB - The FDA classification of endosseous dental implants (EDI) is reviewed. Factors impacting the long-term efficacy of dental implants and the guidelines for development of EDI are enumerated. The role of the ADA in evaluation of EDIs is also discussed. Recommendations for development of performance criteria and reporting format are made. PMID- 1432927 TI - Interactions as seen by an industry representative among the FDA, the ADA, and industry in preparing a restorative material for market. AB - The regulation of a restorative material in the international and the American markets is discussed. The 510(k) process of approval by the Food and Drug Administration allows marketing of safe, effective, and improved materials in the shortest time at the lowest cost. The American Dental Association contributes to developing consensus performance standards in the United States. Acceptance of International Standards Organization standards is discussed. PMID- 1432929 TI - Effect of regulatory and professional guidelines on the development and marketing of a dental device: case history. AB - The FDA encourages organizations such as the ADA to develop voluntary standards for drugs and dental devices. The landmark process of gaining ADA approval of an oral irrigator as the first therapeutic device is described. The process was time consuming and expensive, and obligates the manufacturer to submit all future marketing and advertising claims for ADA review. The ADA should continue to ensure standardized guidelines for all product categories. Education of the dental profession and the consumer concerning the significance of the ADA seal of approval is encouraged. PMID- 1432930 TI - A practitioner's view. PMID- 1432931 TI - What do consumers want? AB - A consumers' advocate discusses the needs of the consumer in evaluating dental products. Although commending the roles of the FDA and ADA in evaluating products, numerous questions are raised and recommendations made concerning advertising claims. PMID- 1432932 TI - A researcher's view. AB - The Food and Drug Administration (FDA), by ensuring that the health care products used by Americans are both safe and effective, provides an essential regulatory function. With respect to the regulation of dental drug products, this researcher perceives that the FDA has not changed or modified its position on a number of issues to reflect new scientific information. Reasons for this inflexibility include the size and ponderousness of the agency, inadequate staff with dental expertise, and a failure to keep current with new dental research findings. The FDA must solve these problems if it wishes to regulate intelligently. The acceptance and certification programs of the American Dental Association ensure that products offered to the profession and the public that bear its seal of acceptance are safe and effective. The ADA's Council on Dental Therapeutics has a long history of staying current on issues in dental research and public health and regularly seeks consultation from eminently qualified experts. Overall, it has done an excellent job over the years in conducting an important voluntary regulatory program. Both the FDA and the ADA benefit and help protect the oral health of the public. PMID- 1432933 TI - Ethical perspectives on the FDA and ADA evaluation of dental products. AB - Contemporary bioethics is concerned with qualitative decisions rather than quantitative decisions. Several examples are discussed including the role of patients as decision makers in their treatment and in their assignment within clinical trial groups. PMID- 1432934 TI - FDA and ADA evaluation of dental products--implications for dentists and their patients: a view from the practitioner. AB - A general practitioner discusses the problems clinicians encounter in trying to evaluate dental materials and devices. Numerous examples are given. The FDA and ADA should provide more information to dentists concerning their role in monitoring dental products. PMID- 1432935 TI - The regulatory process for dental devices: a researcher's view. AB - Comments from the three previous speakers ranged from moderate satisfaction to strong dissatisfaction with the regulatory process. Three different types of research are identified that seem to predict the ease of compliance with the 510(k) process. No one expressed satisfaction with the PMA application. It seems that current evaluation procedures inhibit the developing and marketing of new devices, but foster only enhancements to existing devices. The development of new evaluation methods is advocated to provide fast, inexpensive, but rigorous assessment of the clinical safety and treatment value of new devices. PMID- 1432936 TI - Legal and regulatory developments of the 1990s in oral care products: learning from what has come before. AB - The development of oral care products has occurred faster than congressional enactments regulating these products. Terms such as "cosmetic, drug, and new drug" are defined. A history of scientific publications and common acceptance by experts is necessary for the FDA to categorize a product as "generally recognized as safe and effective" (GRASE). The FDA classification process of the numerous over-the-counter drugs into a few categories, each of which required a three-part approval process, is not complete. Delays in the FDA's OTC review resulted in an "OTC moratorium," which allows new products to enter the market at the owner's risk. The relative risks and benefits of marketing an oral care product with or without an approved New Drug Application are discussed. Increased resources at the FDA are recommended to expedite fairness to manufacturers and to eliminate inappropriate oral care products from the market. PMID- 1432937 TI - The view and responsibility of the advertising agency toward advertising claims. AB - Health care advertising agencies must create communication that is simultaneously creative, scientifically accurate, relevant, within fair balance, simple, motivating, within approved labeling, and approvable by the client, the dental profession, and regulatory bodies. The advertising must also stimulate sales of the product being advertised. Subjective decisions concerning these requirements place the agency and its client at risk for financial losses and embarrassment. PMID- 1432938 TI - Legal implications of using drugs and devices in the dental office. AB - Choosing dental products that are FDA and/or ADA approved is a wise choice concerning their safety and efficacy for approved uses. However, the dentist must show that the product was indicated by a particular patient's needs. Uses of approved dental products in nonapproved ways or use of nonapproved products may be considered as negligence in some malpractice actions, but allowed under standards of reasonableness in other situations. The dentist must be able to justify decisions on a scientific basis. Legal ramifications of various decisions made in the context of difficult prescription choices are discussed. PMID- 1432939 TI - Recommendations. PMID- 1432940 TI - Influences of castration and testosterone on spring to summer changes in release of luteinizing-hormone-releasing hormone in rabbits. AB - Push-pull cannulae were implanted toward the tuberal region of the hypothalamus in ten intact New Zealand male rabbits. In the first experiment, rabbits were perfused at different times after castration: 5-10 days (n = 10), 22-31 days (n = 9) and 50-64 days (n = 8). The release, mean amplitude and mean frequency of luteinizing-hormone-releasing hormone (LHRH) signals from 37 perfusions in ten animals were analysed in intact rabbits and at different times after castration. No significant changes in release of LHRH and in amplitude were observed, but the frequency was significantly higher 22-31 days after castration than in intact rabbits (intact: 0.86 +/- 0.12; castrated: 1.20 +/- 0.13 pulses h-1, P < 0.035; n = 9). In Expt 2, testosterone and placebo Silastic capsules were implanted in the castrated rabbits. Perfusions were performed in the following four periods, defined by season and time after testosterone and placebo implants: (i) spring; before implants, (ii) late spring; 0-2 weeks after implants, (iii) summer solstice; 2-4 weeks after implants and (iv) summer; 4-6 weeks after implants. Castrated rabbits were perfused during spring; castrated rabbits with testosterone capsule implants were perfused during late spring, around summer solstice and in summer and castrated rabbits with placebo implants were perfused during periods (iii) and (iv). Castrated animals with placebo implants showed no significant changes in mean LHRH release and amplitude, although the frequency was significantly higher around the summer solstice period than in castrated rabbits perfused in the spring. In castrated rabbits with testosterone implants LHRH release was significantly higher in late spring than around the summer solstice and in the summer. In addition, the concentrations of LHRH in late spring were significantly higher than those of intact and castrated animals. In contrast, mean LHRH amplitude and frequency did not change. Mean amount of LHRH released and amplitude in castrated rabbits with testosterone implants were significantly lower around the summer solstice than in late spring or summer and compared with intact animals around summer solstice and in castrated rabbits in early spring. These data demonstrate that there were no significant changes in the mean amplitude and release of LHRH after castration from 5 and up to 64 days in rabbits with hypothalamic push-pull cannulae, in contrast to the well established dramatic effect of castration on gonadotrophin concentrations. However, there was a small, but significant, increase in the mean frequency of LHRH pulses 22-31 days after castration compared with values from intact rabbits.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432941 TI - Binding and action of insulin-like growth factors and insulin in bovine luteal tissue during the oestrous cycle. AB - The effect of insulin-like growth factors (IGFs) and insulin on the release of progesterone and oxytocin from bovine corpus luteum was investigated at early (days 5-7), mid- (days 8-12) and late (days 15-18) luteal phases of the oestrous cycle in an in vitro microdialysis system. The expression of specific receptors was evaluated in bovine corpora lutea of the respective luteal stages. A 30 min infusion of IGF-1, IGF-2 (1.3, 13 and 130 nmol l-1) or insulin (13, 130 and 1300 nmol l-1) caused a stimulation of the release of progesterone (P < 0.05). IGF-1 was most effective in releasing progesterone. Oxytocin release from corpora lutea was stimulated by insulin at all doses tested (13-1300 nmol l-1), whereas the IGFs were only effective at the highest dose (130 nmol l-1) applied. The high doses of IGFs (130 nmol l-1) and insulin (1300 nmol l-1) stimulated the release of progesterone and oxytocin throughout the luteal phase (P < 0.05). For all three peptides, greatest stimulation was seen during the late luteal phase (days 15-18 of the oestrous cycle) with the peak of progesterone release directly related to peptide infusion (P < 0.05). In addition, IGF-1 stimulated total release of progesterone (units in 4 h) after the beginning of the stimulation during this phase (P < 0.05). IGF-1 caused a gradual increase of progesterone even beyond the time of peptide perfusion, whereas IGF-2 and insulin stimulated progesterone release only during the peptide perfusion. Distinct receptors for IGF-1 and IGF-2 were present in corpora lutea membrane preparations at all stages investigated. Specific binding for insulin was also seen in all stages of the cycle without any cycle-dependent changes in the amount of binding. The displacement of labelled insulin by unlabelled IGF-1 and IGF-2 did not show the rank of order that has been described as typical for insulin receptors (i.e. insulin > IGF-1 > IGF-2), but comparable binding affinities were observed for the three unlabelled ligands. Specific binding of IGF-2 was markedly higher than that of IGF-1 or insulin throughout the cycle (1.9- and 4.9-fold higher compared with IGF-1 and insulin, respectively). Receptor specificity did not change during luteal development. Binding affinity and capacity of IGF-1 receptor was constant throughout the oestrous cycle. Specific IGF-2 binding increased and showed a positive co-operativity towards the end of the cycle. Specific binding of insulin was not significantly different in the three luteal stages examined. PMID- 1432942 TI - Properties of proteins binding plasma progesterone in pregnant Cape porcupines (Hystrix africaeaustralis). AB - The properties of progesterone-binding proteins in plasma of pregnant Cape porcupines were investigated using radiolabelled progesterone and either progesterone or cortisol as competing ligands as well as native plasma and heated (60 degrees C for 30 min) plasma. The results demonstrated that plasma from pregnant porcupines contains corticosteroid-binding globulin, but that it constitutes a significant portion of plasma progesterone-binding proteins only during the early stages of pregnancy. Corticosteroid-binding globulin of porcupines appears to be as heat labile as that of guinea-pigs. Concentrations of progesterone-binding proteins in plasma increased during pregnancy to reach concentrations at the eleventh week that were 25 times higher than those of progesterone; concentrations increased significantly (r2 = 0.88) with the increase in progesterone concentration. The results indicate that plasma progesterone-binding proteins in Cape porcupines (Old World hystricomorph) are similar in composition to those in guinea-pigs (New World hystricomorph). PMID- 1432943 TI - Characterization of epidermal growth factor receptor in testis, epididymis and vas deferens of non-human primates. AB - The presence of the epidermal growth factor receptor (EGFR) in testis, epididymis and vas deferens of monkeys was demonstrated using a polyclonal antibody (RK2) raised against a peptide-specific sequence of the intracellular domain of the human EGFR. Immunoblotting of membrane preparations revealed a specific band at approximately 170 kDa corresponding to those of controls, A431 and monkey liver cells. Cryostat sections were stained by biotin-streptavidin peroxidase immunocytochemistry. The liver showed positive staining along the basolateral membranes of the hepatocytes lining the sinusoids. The testis showed positive staining indicating the presence of EGFR in Leydig cells, Sertoli cells and peritubular cells. In the epididymis, immunostaining of the EGFR was observed on both the basolateral and the luminal borders of the epididymal epithelium. Immunofluorescence studies revealed a similar pattern of EGFR distribution in the epididymis and indicated that the luminal immunostaining was vesicular. In the vas deferens, positive immunostaining was detected in a pattern very similar to that observed in the epididymis. There was no positive staining in the interstitium of the epididymis or in the smooth muscle cell layers of the vas deferens. The sections of all tissues treated with pre-immune serum were negative. These results suggest that EGF in the primate testis may act at the level of somatic cells. In addition, the basolateral and luminal EGFR staining in the epididymis and vas deferens suggest that these cells respond to an EGF, or EGF-like, source both at the basal, luminal or at both sides of the cells, or that these tissues serve as sites of EGF transcytosis across the epithelium. PMID- 1432944 TI - Rapid transport of seminal immunoglobulin to distal parts of the female reproductive tract in rabbits. AB - Bucks immunized with the bacteriophage-cloning vector fd-tet display strong humoral seminal immunity of 1.5 x 10(6) fd-tet neutralizing units (nu) ml-1. We used this model to study the distribution of seminal immunoglobulin in the female reproductive tract after copulation and artificial insemination. In contrast to artificial insemination, significant (P < 0.01) amounts (147 nu ml-1, i.e. about 1.25 x 10(-4) input ejaculate) of neutralizing activity reached the uterus within 20 min of a single copulation, which is evidence for rapid transport of seminal plasma to distal parts of the tract. Oviducts were also quickly impregnated with antibodies to fd-tet, which persist in the distal compartments for at least 24 h. PMID- 1432945 TI - Immunohistochemical localization of basic fibroblast growth factor within the mouse uterus. AB - Uterine samples were either rapidly frozen in liquid nitrogen or placed in Bouin's fixative. A commercial primary polyclonal antibody made in rabbits against human recombinant basic fibroblast growth factor (bFGF) was used. Western blot analysis indicated that the antibody was specific for bFGF and did not react with acidic FGF. The primary antibody was followed by either goat anti-rabbit immunoglobulin G (IgG) conjugated to the fluorescent phycobiliprotein tracer phycoerythrin or biotinylated goat anti-rabbit IgG and a biotin-avidin-peroxidase complex. Specificity controls using adjacent sections were carried out by (i) substituting normal rabbit sera for the primary antisera, (ii) omitting the primary antisera or (iii) extracting sections with NaCl (2 mol l-1) prior to the immunochemical procedures. No binding of the antibody was observed with any of the specificity control sections. The connective tissue stroma and the basal lamina associated with uterine glandular and surface epithelial layers were positive for bFGF. Localization was not observed within surface or glandular epithelial cells. The basal lamina and endothelial cells associated with blood vessels within the uterus and the smooth muscle cells of the myometrium were positive for bFGF. There were no differences in uterine localization patterns or intensity during the oestrous cycle or after ovariectomy and steroid hormone supplementation. These studies demonstrate the specific localization of bFGF within the mouse uterus. PMID- 1432946 TI - Role of photoperiod in reproductive maturation and peripubertal hormone concentrations in male collared lemmings (Dicrostonyx groenlandicus). AB - Onset of sexual maturation was determined in weanling male collared lemmings exposed to one of three experimental regimens of different photoperiods before and after weaning. Animals gestated in photoperiods of either 16 h light:8 h dark or 8 h light:16 h dark. Those from 16 h light:8 h dark were transferred at 19 days of age to either 20 h light:4 h dark or 8 h light:16 h dark; those gestated under 8 h light: 16 h dark remained in that photoperiod throughout the experiment. After exposure for 15, 20, 25 or 30 days to the postweaning photoperiod, animals were killed and the following parameters assessed: body weight, testes weight, seminal vesicle weight, the presence or absence of epididymal spermatozoa and serum concentrations of prolactin, testosterone and corticosterone. All parameters except serum testosterone were significantly influenced by photoperiod. Animals housed under 8 h light:16 h dark had significantly greater body weights than those housed under 20 h light:4 h dark, a response that differs from that reported for other arvicoline rodents. The group gestated on 16 h light:8 h dark and transferred on day 19 to 8 h light:16 h dark had lower testes and seminal vesicle weights than the other two groups, and mature spermatozoa in the epididymides appeared 5 days later than in the 20 h light:4 h dark group. Serum prolactin was largely undetectable in animals from both 8 h light:16 h dark groups, but all males housed in 20 h light:4 h dark had 2.0-15.0 ng prolactin ml-1. Concentration of serum corticosterone was higher in animals weaned into long photoperiod, and decreased with age. These data indicate that weanling male D. groenlandicus are reproductively photoresponsive, but use a decrease in photoperiod, not static short-photoperiod exposure, to alter the rate of development. Prolactin was largely undetectable in animals exposed to short photoperiod, indicating that high concentrations of this hormone are not important for maturation. Low prolactin concentrations in animals in short photoperiods may mediate the annual moult to white pelage. The short-photoperiod mediated decrease in corticosterone may play a role in seasonal changes in body weight and composition. PMID- 1432947 TI - Modulation of luteinizing hormone and follicle-stimulating hormone in circulation by interactions between endogenous opioids and oestradiol during the peripubertal period of heifers. AB - The aim of this study was to determine whether the decline in oestradiol inhibition of circulating luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during the peripubertal period of heifers is associated with a change in opioid modulation of LH and FSH secretion. Opioid inhibition of LH secretion was determined by response to administration of the opioid antagonist naloxone. Prepubertal heifers (403 days old) were left as intact controls, ovariectomized or ovariectomized and chronically administered oestradiol. Control heifers were used to determine time of puberty. Three weeks after ovariectomy, four doses of naloxone (0.13-0.75 mg kg-1 body weight) or saline were administered to heifers in the treatment groups in a latin square design (one dose per day). Blood samples were collected at intervals of 10 min for 2 h before and 2 h after administration of naloxone. This procedure was repeated four times at intervals of 3 weeks during the time intact control heifers were attaining puberty. All doses of naloxone induced a similar increase in concentration of serum LH within a bleeding period. During the initial bleeding period (before puberty in control heifers), administration of naloxone induced an increase in LH concentration, but the response was greater for heifers in the ovariectomized and oestradiol treated than in the ovariectomized group. At the end of the study when control heifers had attained puberty (high concentrations of progesterone indicated corpus luteum function), only heifers in the ovariectomized and oestradiol treated group responded to naloxone. Opioid inhibition of LH appeared to decline in heifers during the time control heifers were attaining puberty. Heifers in the ovariectomized group responded to naloxone at the time of administration with an increase in FSH, but FSH did not respond to naloxone at any other time. Administration of naloxone did not alter secretion of FSH in ovariectomized heifers. These results suggest that opioid neuropeptides and oestradiol are involved in regulating circulating concentrations of LH and possibly FSH during the peripubertal period. Opioid inhibition of gonadotrophin secretion appeared to decline during the peripubertal period but was still present in ovariectomized heifers treated with oestradiol after the time when age matched control heifers had attained puberty. We conclude that opioid inhibition is important in regulating LH and FSH in circulation in heifers during the peripubertal period. However, opioids continue to be involved in regulation of circulating concentrations of LH after puberty. PMID- 1432948 TI - The effect of pre-ovulatory anaesthesia on ovulation in laparoscopically inseminated domestic cats. AB - Laparoscopic intrauterine artificial insemination (AI) of electroejaculated spermatozoa was used to compare embryo development and conception rates in domestic cats inseminated either before or after ovulation. Females were given a single (100 iu) injection of pregnant mares' serum gonadotrophin (PMSG) followed by either 75 or 100 iu human chorionic gonadotrophin (hCG) 80 h later. Cats were anaesthetized (injectable ketamine HCl/acepromazine plus gaseous halothane) 25-50 h after administration of hCG for laparoscopic assessment of ovarian activity and for transabdominal AI into the proximal aspect of the uterine lumen. At the time of AI, 23 cats were pre-ovulatory (25-33 h after hCG injection) and 30 were post ovulatory (31-50 h after hCG injection). Pre-ovulatory females produced 10.5 +/- 1.1 follicles and no corpora lutea compared with 1.9 +/- 0.5 follicles and 7.5 +/ 0.9 corpora lutea for the post-ovulatory group (P < 0.05). Six days later, the ovaries of nine pre-ovulatory and 12 post-ovulatory females were re-examined and the reproductive tracts flushed. On this day, pre-ovulatory cats produced fewer corpora lutea (2.8 +/- 1.5; P < 0.05) and embryos (0.4 +/- 0.3; P < 0.05) than post-ovulatory females (18.9 +/- 3.3 corpora lutea; 4.6 +/- 1.2 embryos). Two of the 14 cats (14.3%) inseminated before ovulation and not flushed became pregnant compared with 9 of 18 cats (50.0%) inseminated after ovulation and up to 41 h after hCG injection (P < 0.05). These results indicate that ovulation in cats is compromised by pre-ovulatory ketamine HCl/acepromazine/halothane or laparoscopy or by both and that electroejaculated spermatozoa deposited by laparoscopy in utero, after ovulation, result in a relatively high incidence of pregnancy. Because ovulation usually occurs 25-27 h after injection of hCG, the lifespan for fertilization of the ovulated ovum appears to be at least 14 h in vivo in cats. PMID- 1432949 TI - Vitrification of bovine blastocysts obtained by in vitro culture of oocytes matured and fertilized in vitro. AB - Two experiments were conducted to assess the viability of bovine blastocysts obtained by in vitro fertilization of oocytes matured in vitro (IVM-IVF) and cryopreserved by vitrification. In Expt 1, the optimal concentrations of glycerol and 1,2-propanediol in the basic medium (modified TCM199) for cooling and warming without formation of ice crystals were determined by plunging the solution into liquid nitrogen and then warming it in a water bath at 15 degrees C; when both glycerol and 1,2-propanediol were present in the solution (> 45% v/v), vitrification of the medium was observed. In Expt 2, IVM-IVF blastocysts were equilibrated to the mixture of glycerol and 1,2-propanediol (0% to 45%) at 15 degrees C in a stepwise manner as follows: (i) in one step, for 18 min to the final vitrification solution; (ii) in two steps, for 8 min in the first step and 10 min in the second step; (iii) in four steps, for 4 min in the first three steps and 6 min in the last step; (iv) in eight steps, for 2 min in each step, but 4 min in the last step; and (v) in 16 steps, for 1 min in each step, but 3 min in the last step. After removal of cryoprotectants, the blastocysts were cultured for 24 h in vitro. The survival rates for the embryos equilibrated in 1, 2, 4, 8 and 16 step(s) were 56, 89, 100, 100 and 100%, respectively. The blastocysts equilibrated in 1, 2, 4, 8 and 16 steps were vitrified by plunging the straws containing them into liquid N2, thawed and cultured in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432950 TI - Changes in the hypothalamic-hypophyseal axis of mares in relation to the winter solstice. AB - In mares, the amount of gonadotrophin-releasing hormone (GnRH) is low in the hypothalamus during seasonal anoestrus, but by early spring, concentrations of GnRH are high. The timing of this response was characterized more precisely by determining concentrations of GnRH in hypothalamic tissue collected immediately before and at various times after the winter solstice (22 December 1986). Ovaries, pituitary gland, hypothalamus and a blood sample were collected from six groups of mares (6-12 mares per group) at death, 1 week before day of the winter solstice and 1, 2, 3 and 12 weeks afterwards. No significant changes in weight of the anterior pituitary gland or concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were observed in the anterior pituitary gland (P > 0.1). Mean diameter of the largest follicle, number of follicles > or = 20 mm in diameter and concentrations of LH and FSH in serum remained unchanged for weeks -1 to +3 (P < 0.05), then increased significantly by week 12 (P < 0.001). Content and concentration of GnRH in the median eminence was low at -1 week, increased gradually (P < 0.05) to a maximum by +1 week, then decreased gradually (P < 0.05) to low values at 12 weeks. Means (+/- SEM) for -1, +1 and +12 weeks were 33.5 +/- 5.5, 117.7 +/- 18.6 and 29.8 +/- 3.7 ng GnRH, respectively. Mean content of GnRH in the preoptic area of the hypothalamus showed a reciprocal pattern.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432951 TI - Uptake of exogenous DNA by mammalian spermatozoa: specific localization of DNA on sperm heads. AB - When mouse spermatozoa were briefly exposed in culture to radioactively labelled DNA (pSV2CAT plasmid), radioactivity could be detected by high-resolution autoradiography on the surface and within the nucleus of the spermatozoa. Spermatozoa from other mammalian species (boar, bull, man) could also bind foreign DNA. With the exclusion of human spermatozoa, which in most experiments showed very low labelling values, labelling percentages (evaluated by light microscope autoradiography) ranged between 39 and 78%. In all four species the DNA-binding ability was mainly confined to a specific region of the sperm head (equatorial segment and postacrosomal region), and the sperm-DNA association kinetics were rapid (maximum values were reached within 20-40 min). The data also indicate that factor(s) in seminal plasma might protect spermatozoa from accidental transfection by foreign DNA that may be present in the genital tracts from bacterial or viral sources. PMID- 1432953 TI - Effects of glucose, glutamine, ethylenediaminetetraacetic acid and oxygen tension on the concentration of reactive oxygen species and on development of the mouse preimplantation embryo in vitro. AB - Analysis over the first 48 h of development in vitro from the one-cell stage to the early four-cell stage indicated that (i) ethylenediaminetetraacetic acid (EDTA) exerts the major beneficial effect on culture to the blastocyst stage of F1 and MF1 embryos, (ii) glutamine assists development of MF1, but not F1, embryos to the blastocyst stage and probably functions as part of a metabolic response to oxidative damage to mitochondria and (iii) exposure to glucose at some time during early cleavage is essential for full development to blastocysts. None of the culture conditions examined affected significantly the increase in concentration of reactive oxygen species in late two-cell embryos in vitro, although F1 embryos in vitro often had lower peroxide concentrations than MF1 embryos. A decline in oxygen tension from 20 to 50% had no consistent effect on culture to the blastocyst stage or production of reactive oxygen species. Aminooxyacetate, an inhibitor of transaminase activity, prevented non-blocking embryos from developing beyond G2 of the second cell cycle. It is concluded that the chelation of transitional metals provides the most effective method of overcoming the block to development in vitro. PMID- 1432954 TI - Changes of progesterone content of rat uterine flushings in relation to serum concentrations of progesterone during the oestrous cycle. AB - Uterine fluid was collected from four-day cyclic rats at each stage of the oestrous cycle and assayed for progesterone and protein content. Progesterone was determined by radioimmunoassay either after ethanol (or 2.5% NaOH) denaturation of proteins from uterine flushings ('total' progesterone) or without protein denaturation ('ether-extractable' progesterone). The amount of 'ether extractable' progesterone in the lumen was constant from metoestrus to pro oestrus (340 pg per uterus) but lower in oestrus (200 pg per uterus). However, 'total' progesterone content of uterine fluid was subject to cyclic variations and was highest in dioestrus (890 pg per uterus) and lowest in oestrus (350 pg per uterus), in contrast to serum progesterone which is lowest in dioestrus and highest in oestrus. Protein content of uterine flushings peaked to 780 micrograms per uterus in pro-oestrus then fell to about 140 micrograms per uterus until the end of the oestrous cycle. Changes in protein content of the lumen were followed by qualitative variations since the mean amount of 'bound' progesterone ('total' progesterone minus 'ether-extractable' progesterone) released per milligram of denatured lumen protein rose from 1.8 pmol in pro-oestrus to 18.2 pmol in dioestrus. The changes of luminal 'bound' progesterone during the oestrous cycle suggest that progesterone binding to luminal proteins could be an important modulator of progesterone action in rat uterus. Moreover, the variations in progesterone content of the lumen, irrespective of serum progesterone concentrations, are consistent with the hypothesis that progesterone synthesis occurs in the uterus. PMID- 1432955 TI - Effect of macrophages on proliferation of granulosa cells in the ovary in rats. AB - The effect of macrophages on proliferation of granulosa cells was examined in gonadotrophin-primed immature female rats. The mouse anti-rat macrophage monoclonal antibodies TRPM-2 and TRPM-3 were used and macrophages were observed in the granulosa layer and antrum of follicles and in corpora lutea and stroma around follicles. There was no difference in distribution between TRPM-2-positive cells and TRPM-3-positive cells. Macrophages with some cytoplasmic vacuoles of various sizes were also demonstrated in growing follicles. The average ratios of macrophages to granulosa cells in preantral, antral and mature follicles were 0.008, 0.007 and 0.002, respectively. Labelling with [3H]thymidine of granulosa cells cultured with peritoneal macrophages was significantly greater and the labelling index peaked to 25.0% when the ratio of macrophages to granulosa cells was 0.01, compared with the value of 14.2% when the granulosa cells were cultured alone. This ratio of macrophages to granulosa cells was similar to that in the preantral and antral follicles in vivo. These results suggest that macrophages participate in promoting proliferation of granulosa cells as local mediators in growing follicles. PMID- 1432952 TI - Anti-ovary antibodies after attempts at human in vitro fertilization induced by follicular puncture rather than hormonal stimulation. AB - Anti-ovary antibodies (AOA) have been detected in serum samples of women undergoing in vitro fertilization (IVF). High concentrations of these antibodies have been found in women who have had several IVF attempts and they appear to correlate with reduced chances of pregnancy. In this paper, AOA were assayed sequentially in a series of 140 IVF candidates to investigate the respective roles of hormonal stimulation and follicular puncture in inducing the autoimmune response. Serum was obtained 8 days after the beginning of ovarian human menopausal gonadotrophin (hMG) stimulation, then 15 days after follicular puncture. Significantly higher concentrations of IgG (P < 0.0001) AOA were observed in the second series of samples than in the first, suggesting that ovarian trauma and not hormonal stimulation is responsible for triggering antibody production. In the whole group, there was a negative correlation between IgM levels after puncture and oocyte numbers (P < 0.05). Among 'immune-responder' women, the concentrations of IgA AOA (P = 0.01) in the first sample, and of IgG (P = 0.01) or IgA AOA (P < 0.05) in the second, correlated with fewer oocytes after stimulation. There was no variation in the mean concentrations of AOA in women who achieved pregnancy. PMID- 1432956 TI - Quantitative fluorometry of abnormal mouse sperm nuclei. AB - An extensive quantitative analysis of deformed mouse spermatozoa was undertaken. Improvements over previous studies included the isolation and purification of sperm nuclei, a multifaceted analytical approach using several fluorochromes and the analysis of individual nuclei classified into shape categories. Malformed sperm nuclei in BALB/c mice could not be distinguished from normal ones in terms of total and basic proteins, sulfhydryl and disulfide group concentration, DNA concentration and chromatin organization. The shape of sperm nuclei is therefore probably determined by the manner in which the internal biochemical components are assembled. PMID- 1432957 TI - Lack of effect of relaxin on oxytocin output from the porcine neural lobe in vitro or in lactating sows in vivo. AB - Oxytocin was measured in incubates and perifusates of neurosecretosomes prepared from sow neural lobes (n = 50) and in incubates of isolated neural lobes (n = 5). In none of these preparations was oxytocin output affected by exposure to purified porcine relaxin (at concentrations up to 10(-7) mol l-1). Moreover, in lactating sows (n = 9), 6-10 days post partum, the administration of porcine relaxin (1.5 or 3.0 mg) intravenously, immediately before a suckling episode, did not affect the plasma oxytocin profile compared with saline treatments (within sow) nor did it alter suckling behaviour or the weight gain of the litter. In all sows, a spike (25-75 pg ml-1) of oxytocin was measured during milk ejection coincident with suckling. These results suggest that porcine relaxin does not affect oxytocin release in suckling sows in contrast to reported findings in rats. The data also support the view that porcine relaxin could be used at farrowing without adverse effects on suckling. PMID- 1432958 TI - Relationship between the onset of oestrus, the preovulatory surge in luteinizing hormone and ovulation following oestrous synchronization and superovulation of farmed red deer (Cervus elaphus). AB - The timing of ovulation relative to the onset of oestrus and the preovulatory surge in luteinizing hormone (LH) was studied in red deer following treatments to synchronize oestrus and induce either a monovulatory or superovulatory response. Mature hinds (n = 36) were allocated randomly to two mating groups (n = 16 + 20), with respective treatments staggered by 4 weeks during the 1990 rut (March April). Each hind was treated with an intravaginal controlled internal drug releasing (CIDR)-type S device for 14 days. Treatments to induce a monovulatory response included CIDR device alone (treatment A; n = 4 + 8) and additional injection of 200 iu pregnant mares' serum gonadotrophin (PMSG) at device removal (treatment B; n = 4 + 4). Treatments to induce a superovulatory response included injections of 200 iu PMSG and 0.5 units ovine follicle-stimulating hormone (FSH) at about time of removal of CIDR devices (treatment C; n = 4 + 4) and further treatment with gonadotrophin-releasing hormone (GnRH) analogue 18 h after removal of CIDR devices (treatment D; n = 4 + 4). The hinds were run with crayon harnessed stags from insertion of CIDR devices (12 March or 9 April) and blood samples were taken every second day to determine plasma progesterone. Further blood samples were collected for determination of plasma LH and progesterone via indwelling jugular cannulae every 2 h for 72 h from removal of CIDR devices. Hinds were allocated randomly to an initial ovarian examination by laparoscopy at either 16 or 20 h (A and B), or 12 or 16 h (C and D) after the onset of oestrus, with laparoscopy repeated at intervals of 8 h until either ovulation was recorded (A and B), or for four successive occasions (C and D). All hinds received cloprostenol injections 15 days after device removal. A total of 28 hinds (78%) exhibited oestrus and a preovulatory LH surge, with mean (+/- SEM) times to onset of oestrus of 44.6 +/- 1.0 h (A; n = 7), 37.4 +/- 2.0 h (B; n = 7), 16.3 +/- 1.7 h (C; n = 6) or 14.0 +/- 1.7 h (D; n = 8). Failure to exhibit oestrus or LH surge was most prevalent among hinds in treatment A early in the rut.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1432959 TI - Cytogenetic analysis of reconstituted one-cell mouse embryos derived from nuclear transfer of fetal male germ cells. AB - Micromanipulation techniques were used to produce reconstituted one-cell mouse embryos after the fusion of fetal male germ cells 15.5 day post coitum with enucleated secondary oocytes. At this stage of development, male fetal germ cells are arrested at G1 of mitotic interphase. Two distinct populations of germ cells, differing in size and ploidy, were isolated from the genital ridge of a mid-term fetus. Oocytes that had received male germ cells from the population of smaller (mononuclear) germ cells developed as diploid one-cell reconstituted embryos. When the same procedures were used to produce reconstituted one-cell embryos using male fetal germ cells from a population of larger (multinucleate) cells, they exhibited ploidy of either 4x, 6x or 8x at metaphase of the first cell division. Although most reconstituted embryos (90 and 96%) developed to the two cell stage, the proportion of embryos receiving small germ cells developed to blastocysts was much higher (62%) than that receiving large germ cells (4%). These studies indicate that not all fetal germ cells are diploid before the onset of meiosis and have identified procedures to produce reconstituted embryos from fetal germ cells that do not carry genome or chromosome anomalies. PMID- 1432960 TI - Reduction in endometrial neutrophils in proximity to implanting rat blastocysts. AB - An antiserum to rat neutrophils was raised and used to follow the distribution of endometrial neutrophils during the peri-implantation period. Uteri from four pregnant and four pseudopregnant rats killed at 14:00, 17:00, 20:30 and 23:00 h on day 5 of pregnancy and 09:00 h on day 6 were sectioned. Four sections from each of four implantation sites and four intersites from each rat were immunostained. There was wide variability among rats in the number of endometrial neutrophils, but a nested analysis of variance showed significantly fewer neutrophils at implantation sites than at intersites from 20:30 h onwards. This difference was primarily due to the presence of more neutrophils in intersite regions of the endometrium. The results from this study do not support a role for neutrophils in the implantation-associated increase in microvascular permeability or decidualization in rats. PMID- 1432961 TI - Effect of fibronectin on early embryo development in cows. AB - Two-cell bovine embryos produced in vitro were cultured in serum-free medium containing the soluble glycoprotein fibronectin (50 micrograms ml-1) to study the function of the extracellular matrix in early development. Some of the embryos (48/164, 29.3%), developed beyond the 16-cell stage compared with none of the 179 controls. Fibronectin at lower (5 micrograms ml-1) or higher (300 micrograms ml 1) concentrations did not promote embryo development (0/89 and 0/82, respectively). Indirect immunofluorescence demonstrated the presence of both fibronectin and its receptor on the surface of eight-cell embryo blastomeres, and biotinylated fibronectin demonstrated that exogenous fibronectin could cross the zona pellucida. These results, demonstrating the successful culture of bovine embryos in serum-free medium, support the hypothesis that the extracellular matrix, specifically fibronectin, plays a role in early development of bovine embryos. PMID- 1432962 TI - Fetal viability and fetal growth after prolonged uterine contractions induced by progesterone withdrawal in late pregnancy in rats. AB - The hypothesis that sustained uterine contractile activity is the direct cause of fetal death after progesterone withdrawal in late pregnancy in rats was investigated. Pregnant rats were subjected to progesterone withdrawal on day 15 of pregnancy by injecting 2 mg mifepristone (RU 486) kg-1 or by ovariectomy with oestradiol replacement (200 ng day-1). Uterine contractile activity (force and frequency) at 4 h, but not at 2 h, in rats injected with mifepristone was significantly higher than in rats injected with vehicle. The contractile activity in mifepristone-treated rats remained higher than in control rats, at 12, 24 and 48 h. Fetal viability 36 h after mifepristone injection, when uterine contractions had lasted for 32 h, was not significantly different from fetal viability in rats injected with vehicle, but at 42 h after mifepristone injection, fetal viability was significantly reduced. In ovariectomized rats, uterine contractile activity at 12, 24, 36 and 48 h, but not at 8 h, was significantly greater than in ovariectomized rats with progesterone replacement (4 mg day-1). Fetal viability at 42 h after the operation, when uterine contractions had lasted for 30 h, was not significantly reduced, but it was significantly reduced at 48 h. When ovariectomized rats had been left to develop uterine contractions for a period before progesterone was injected, deprivation of progesterone and prolonged uterine contractions for about 30 h did not reduce fetal viability or fetal growth determined on day 18, but it did so 3 days later, on day 21. Administration of 5 mg isoxuprine kg-1 twice a day, which suppressed uterine contractions, improved fetal viability in ovariectomized rats at the earlier stage, but not at the later stage. Nevertheless, isoxuprine did improve fetal growth at the later stage in these ovariectomized rats. It is concluded that increased uterine contractile activity sustained for 32 h or less does not reduce fetal viability, but longer periods of contraction may be the cause of fetal death. PMID- 1432963 TI - Involvement of interleukin 2 receptors in conceptus-derived suppression of T and B cell proliferation in horses. AB - The mechanism by which a horse conceptus-derived immunosuppressive factor (HCS) of M(r) > 100,000 inhibits lymphocyte proliferation was investigated. The factor was obtained from the culture supernatants of 20-day-old horse conceptuses; activity, identified by reduced uptake of [3H]thymidine by mitogen-stimulated lymphocytes, was greatest (P < 0.01) in cultures stimulated by mitogen from pokeweed. HCS also suppressed cell proliferation stimulated by phytohaemagglutinin (P < 0.01), but had no effect on lipopolysaccharide stimulated cells (P > 0.05). Data from a fluorescence-activated cell sorter indicated that supplementation with HCS reduced the number of T cells in phytohaemagglutinin-stimulated cultures and suppressed proliferation of T and B cells in pokeweed-mitogen-stimulated cultures compared with controls. Cell proliferation was greater (P < 0.01) in cultures supplemented with HCS 24 h after stimulation than in those treated at the start of stimulation, and was even greater (P < 0.01) when cells were treated 48 h after stimulation. The removal of HCS from treated lymphocyte cultures resulted in complete recovery of cell responsiveness, and stimulated proliferation of treated cells did not differ (P > 0.05) from that of control cells. The addition of stimulated equine lymphocyte supernatant to cultures supplemented with HCS did not significantly increase (P > 0.05) cell proliferation in response to pokeweed mitogen. Addition of recombinant human interleukin 2 (rIL-2) to HCS-treated cultures did not alter the suppressive activity of HCS, although cell proliferation was greater in cultures supplemented with rIL-2 than in controls (P < 0.01). HCS inhibition of IL-2 receptor (IL-2R) function was investigated using an IL-2-dependent murine cytolytic T lymphocyte cell line; the fraction of HCS of M(r) > 100,000 had no effect (P > 0.05) on proliferation of IL-2-dependent murine cytolytic T lymphocyte cells induced by rIL-2. Together, these data suggest that HCS suppresses proliferation of T lymphocytes during the early stages of cell activation by inhibiting IL-2R interaction and that this suppression interferes with interactions between T cells and B cells, thereby also indirectly inhibiting proliferation of B cells. The potent immunosuppressive capacity of HCS may be one factor responsible for inhibiting cell-mediated fetal allograft rejection during pregnancy. PMID- 1432964 TI - Androgenic control of polyamine concentrations in rat epididymis. AB - Unilateral orchidectomy resulted in a significant decrease in tissue content of putrescine and polyamines. However, no differences were detected when the results were expressed in terms of ng g-1 tissue. At 48 h after bilateral orchidectomy, a significant decrease in putrescine content was observed, but spermidine and spermine content were unaffected. The observed decrease in putrescine was prevented by treatment with testosterone propionate, but neither spermidine nor spermine were affected. Bilateral orchidectomy resulted in a significant decrease in the tissue content of putrescine, spermidine and spermine after 7 days. Treatment with testosterone propionate increased the content of putrescine, spermidine and spermine in the epididymis by about 200%, 92% and 34%, respectively. When results were expressed as nmol g-1, a significant decrease after castration in putrescine and spermidine, but not in spermine, was observed. Treatment with testosterone propionate restored putrescine concentration, but had no effect on spermidine and spermine concentrations. In castrated rats treated with testosterone propionate, the anti-androgen flutamide abolished the effect of the androgen on putrescine and spermidine content, but there was no effect on spermine. Acetylputrescine was not detected in the epididymis, while acetylpolyamines were detected at much lower concentrations than polyamines. After bilateral orchidectomy there was a decrease in the tissue content of all acetylpolyamines and an increase in their tissue concentration. The effect of castration on acetylpolyamine content was reversed by testosterone propionate treatment. We conclude that an active synthesis of polyamines occurs in the rat epididymis, and that this process depends upon the androgen environment. Regulation of ornithine decarboxylase activity appears to be the main step that is controlled by androgens. PMID- 1432965 TI - Increase in testosterone sensitivity induced by constant light in relation to melatonin injections in rats. AB - In this experiment we investigated whether the lack of the nocturnal melatonin peak under constant light would cause an increase in testosterone sensitivity. Castrated rats were kept under periodic or constant light for one week. They received a daily injection of vehicle, testosterone propionate (125 micrograms), melatonin (50 micrograms) or testosterone plus melatonin (125 micrograms + 50 micrograms). Serum and pituitary gonadotrophins and pineal melatonin were measured at the end of the experiment. Under constant light, testosterone injections reduced the serum luteinizing hormone concentration in castrated rats to that in intact rats, but, under periodic light, the decrease was smaller. Melatonin did not reverse the stronger effect of testosterone under constant light. The serum melatonin peak produced by the exogenous melatonin injection had a higher amplitude, shorter duration and earlier appearance than the physiological melatonin peak. Exogenous melatonin did not modify the physiological melatonin secretion, measured either as serum melatonin concentration or pineal melatonin content on the consecutive day. We conclude that the increase in testosterone negative feedback sensitivity of castrated rats under constant light was not due to the absence of the nocturnal melatonin pulse. PMID- 1432966 TI - Evidence for an intrinsic control of myometrial contractile periodicity in sheep during pregnancy. AB - Reduction in concentration of prostaglandins in plasma by administration of sodium meclofenamate to pregnant sheep failed to alter the frequency or duration of electromyographic activity bursts or the response to oxytocin of myometrial tissue transplanted to the omentum. However, a significant (P < 0.05) delay (8.6 +/- 3.8 versus 1.3 +/- 0.3 min) in the myometrial response to oxytocin was observed when the hormone was administered 1 min after a spontaneous burst of electromyographic activity compared with 15 min after a burst, indicating a period of refractoriness. Similarly, the myometrial threshold for electrical stimulation was higher at 10-25% of the interval between contractions than close to the expected time of the next contraction. Stimulation of the myometrium at intervals of 30 s revealed a cycling of the electrical stimulation threshold: significantly higher voltages were required to elicit responses between spontaneous bursts of electromyographic activity (18.0 +/- 2.2 V) than during bursts (11.3 +/- 1.6 V). In contrast, there was no voltage differential in animals close to labour (< 24 h). These data provide no evidence to support a role for prostaglandins in the generation of contractions during pregnancy, but suggest that periodicity of contractions is associated with inherent changes in myometrial responsiveness to stimulation, which could occur as a result of a cycling of the resting membrane potential. PMID- 1432967 TI - Effect of treatment with methylprednisolone on duration of pseudopregnancy and on macrophages and T lymphocytes in rabbit corpora lutea. AB - The potential role of macrophages and T lymphocytes in the destruction of the corpus luteum at the end of the luteal phase was investigated by treating pseudopregnant rabbits with the immunosuppressant glucocorticoid methylprednisolone. Eleven specific pathogen-free New Zealand White rabbits were injected with pregnant mares' serum gonadotrophin (40 iu, i.m.), followed 2 days later by human chorionic gonadotrophin (40 iu, i.v.) to stimulate ovulation. The following day (day 1 of pseudo-pregnancy) all animals had an oestradiol-filled Silastic capsule implanted s.c., to ensure that oestradiol, the luteotrophic hormone in this species, would not be limiting. From day 10 of pseudopregnancy, three animals were injected with a low dose of methylprednisolone (2 mg kg-1 per day) until day 20. Three other animals were injected with a higher dose of methylprednisolone (20 mg kg-1 per day) from day 13 of pseudopregnancy until day 19. Five animals served as control, vehicle-injected animals. Blood samples were taken at intervals and assayed for progesterone. Immunofluorescence was used to stain luteal tissue for macrophages, T lymphocytes and class II antigens, and positive cells were counted under high-power magnification. Methylprednisolone treatment reduced (by about 70%), but did not eliminate, the macrophages in the regressing corpora lutea. In contrast, the high dose of methylprednisolone essentially eliminated T lymphocytes, and reduced (by about 90%) the number of cells expressing class II antigen in the luteal tissue. Despite the effects of methylprednisolone on these cells, serum progesterone profiles were not altered by treatment with methylprednisolone, and pseudopregnancy was of normal duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432968 TI - Seasonal testosterone pattern in Hawaiian monk seals (Monachus schauinslandi). AB - Blood samples from four captive male Hawaiian monk seals were collected at intervals of one month for one year for testosterone assay. Plasma testosterone concentrations, measured by radioimmunoassay, revealed a clear seasonal pattern. The lowest mean testosterone concentration (0.09 +/- 0.04 ng ml-1) occurred in January, and the highest (1.78 +/- 0.40 ng ml-1) in June. The seasonal occurrence of births and of injuries related to mating in wild populations of Hawaiian monk seals showed a distinct association with the period of high testosterone. This study supports other data that indicate that the Hawaiian monk seal is a seasonal breeder and is reproductively active for longer than monachine seals that live in higher latitudes. PMID- 1432969 TI - Ca(2+)-related changes in the mouse sperm capacitation state: a possible role for Ca(2+)-ATPase. AB - Mammalian spermatozoa require extracellular Ca2+, some of which must be internalized, to undergo complete capacitation. At a critical threshold, a rise in intracellular Ca2+ will trigger acrosomal exocytosis. We used chlortetracycline (CTC) fluorescence patterns to assess changes in the capacitation state of mouse spermatozoa after incubation under various conditions that would affect their intracellular Ca2+ concentrations. Under standard conditions with 1.80 mmol CaCl2l-1 known to support capacitation within 120 min and subsequent fertilization in vitro, a rise in the number of capacitated, acrosome-intact cells (B pattern) was observed over the first 60 min, followed by a decline. A detectable increase in capacitated, acrosome-reacted cells (AR pattern) coincided with the maximum of B pattern cells and a continued rise was observed over the following 60 min. With incubation in 3.60 mmol Ca2+l-1, the rise in AR cells began at 30 min, suggesting that this treatment accelerates capacitation. Introduction of ionophore A23187 at 15 min to cells in standard Ca2+ produced a similar but even more rapid response, with a maximum in B pattern cells and a noticeable rise in AR cells within 10 min. Thus ionophore-treated cells proceed through capacitation, but do so very quickly. However, ionophore in the presence of 90 mumol Ca2+l-1 could promote transition from the uncapacitated F pattern to the capacitated B pattern, but could not trigger acrosomal exocytosis, indicating that the latter requires high extracellular Ca2+. After preincubation in Ca(2+)-deficient medium, most cells exhibited the uncapacitated F pattern and the introduction of millimolar Ca2+ altered this distribution only slowly, over a period of 50 min. In contrast, preincubation in 90 mumol Ca2+l-1 resulted in a minority of F pattern cells and, within 10 min of millimolar Ca2+ introduction, a significant increase in AR cells was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432970 TI - Experimental induction of luteal cyclicity in roe deer (Capreolus capreolus). AB - Concentrations of progesterone and luteinizing hormone in plasma were analysed for two consecutive years in samples from nonpregnant female roe deer. Three animals were treated with monthly prostaglandin injections (325 micrograms cloprostenol) from October 1989 to April 1990 and from October 1990 to March 1991, and three were kept as controls. In control animals, a small increase in progesterone concentrations in July 1990 occurred at the same time as the commencement of the rut in other husbanded roe deer. In prostaglandin-treated animals, progesterone concentration was high at the time of the rut and remained so until late February 1990. After the next rut (August 1990), progesterone concentration remained high until March 1991. Between October and February-March, injections of prostaglandins induced dramatic, but temporary (lasting 72 h), decreases in plasma progesterone concentrations, indicating luteal regression and subsequent ovulation. We infer that roe deer can ovulate repeatedly and should therefore not be regarded as an obligate monoestrous species. PMID- 1432971 TI - Stimulation of immunoreactive inhibin production by preimplantation embryos during early pregnancy in the marmoset monkey (Callithrix jacchus). AB - The role of the embryo in promoting increased plasma concentrations of immunoreactive inhibin after conception in the marmoset monkey was determined by flushing embryos from the uterus between days 5 and 9 after ovulation (implantation commences on days 11-12). Blood samples were taken from each animal (three times a week) after ovulation until the end of the luteal phase. Plasma inhibin concentrations were measured using a radioimmunoassay based on antisera against a synthetic fragment of the alpha-subunit of human inhibin. When embryos were flushed on days 5 and 6 (n = 6) after ovulation inhibin concentrations did not exceed 250 ng ml-1 for the duration of the luteal phase. In contrast when embryos were flushed on days 7 (n = 4), 8 (n = 4) and 9 (n = 3) maximum concentrations of inhibin always exceeded 250 ng ml-1, reaching > 400 ng ml-1 when embryos were flushed on days 8 and 9. Inhibin concentrations remained high for the duration of the luteal phase, which varied in length between 20 and 32 days. Significantly (P < 0.01) higher mean plasma concentrations of immunoreactive inhibin were first recorded on days 7-8 after ovulation in animals that had embryos flushed on days 7, 8 and 9 compared with concentrations in animals that had embryos flushed on days 5 and 6. Inhibin could not be detected in the medium of embryos cultured for up to 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432972 TI - Intracellular free Ca2+ concentration in fowl spermatozoa and its relationship to motility and respiration in spermatozoa. AB - The ability of fowl spermatozoa to accumulate and de-esterify the intracellular fluorescent Ca2+ indicator fura-2 was established. The cytosolic Ca2+ concentrations, measured by this technique, did not change after the addition of 1 mmol EGTA l-1. Subsequently, addition of the calcium ionophore A23187 caused a reduction in cytosolic Ca2+ concentrations, presumably by efflux of Ca2+ from the spermatozoa. Intracellular free Ca2+ concentrations were then significantly increased by the addition of 1 mmol CaCl2 l-1. The motility of demembranated spermatozoa gradually decreased after the addition of EGTA alone or EGTA with A23187, but was instantly restored by the addition of CaCl2 in the presence of both EGTA and A23187. Unlike demembranated spermatozoa, intact spermatozoa maintained their motility, even after the addition of EGTA, but their motility was reduced by the addition of A23187 in the presence of EGTA. The addition of A23187 also reduced the rate of oxygen consumption, but not the ATP concentrations in intact spermatozoa. These results demonstrate that the motility and respiration of fowl spermatozoa are strongly influenced by their intracellular Ca2+ concentrations. PMID- 1432973 TI - How does transferrin overcome the in vitro block to development of the mouse preimplantation embryo? AB - Transferrin promotes development of mouse embryos through the two-cell block in vitro. Uptake of transferrin into blastocysts was shown to occur by both receptor mediated and nonspecific pathways, but neither pathway was used to a detectable extent by embryos before the eight-cell stage. Conversely, the dialysis of culture medium, non-permissive for development through the two-cell block, against a solution of transferrin rendered it capable of supporting development. It was therefore concluded that transferrin exerts its supportive effect on development in vitro via its chelating effects. PMID- 1432974 TI - Role of monoclonal antibody J-23 in inducing acrosome reactions in capacitated mouse spermatozoa. AB - A monoclonal antibody (J-23) to the 15 kDa component on the sperm head, the acceptor, which functions in zona binding, was shown to induce the acrosome reaction in capacitated cells, but not in fresh cells. The antibody recognized its epitope in the acrosomal cap region of fresh spermatozoa and in the equatorial region on washed and capacitated spermatozoa. However, equatorial expression did not depend on the acrosome reaction, since washing fresh spermatozoa increased the percentage with equatorial fluorescence, but did not increase the percentage with reacted acrosomes. The data indicate that the acrosome reaction can be induced in capacitated spermatozoa in the absence of zona glycoproteins. PMID- 1432975 TI - Biosynthesis of platelet-activating factor by two-cell mouse embryos. AB - Incubation of two-cell mouse embryos with a range of radiolabelled compounds resulted in the incorporation of label into platelet-activating factor (PAF; 1-O alkyl-2-acetyl-sn-glycero-3-phosphocholine) in the culture media. The demonstration that known precursors ([1-14C]hexadecanol, [1-3H]hexadecanol, 1-O [alkyl-1'2'-3H]lyso-PAF, 1-O-[alkyl-1'2'-3H]acetyl-glycerol and [methyl 3H]choline chloride) were incorporated into PAF showed that embryo-derived PAF biosynthesis occurred via pathways present in other PAF-producing cells. The enzyme responsible for the formation of the ether linkage of the PAF molecule, alkyl-dihydroxyacetone-phosphate synthase, was present in the preimplantation embryo as [1-3H]hexadecanol was incorporated into PAF. Incorporation of label from alkylacetyl-glycerol and choline chloride into lyso-PAF was also observed, suggesting a role for lyso-PAF in the metabolism of embryo-derived PAF. Incubation of embryos with each of three [14C]carbohydrate energy substrates resulted in the incorporation of label into PAF in culture media, indicating that the composition of embryo culture media is important in the synthesis of PAF precursors. Incorporation of label from [2-14C]pyruvate was greatest and is consistent with the suggestion that pyruvate is the major energy source at the two-cell stage of development. L-[U-14C]Lactate was also incorporated into embryo derived PAF, but the mean amount incorporated relative to the concentration of labelled substrate in the medium was 40 times less. The incorporation of D-[U 14C]glucose into PAF was 2405 times less than that from pyruvate, relative to the concentration in the medium. PMID- 1432976 TI - Effect of sperm penetration in vitro on completion of first meiosis by bovine oocytes arrested at various stages in culture. AB - Bovine oocytes cultured for 12-20 h in TC-199 were incubated for 24 h in fertilization medium, Brackett and Oliphant medium with bovine serum albumin (10 mg ml-1), caffeine (5 mmoll-1) and heparin (10 micrograms ml-1), with or without frozen-thawed spermatozoa. High penetration rates (93-96%) and significantly (P < 0.001) higher maturation rates were obtained in oocytes incubated with (93-100%) than without (62-72%) spermatozoa. However, when oocytes at the germinal vesicle stage were cultured for 44 h fertilization medium, maturation of oocytes to metaphase II was reduced. However, all oocytes that were first cultured for 20 h and further for 24 h with spermatozoa were penetrated and 40% of the penetrated oocytes reached metaphase II. All of the remaining oocytes that did not mature arrested at the stages of condensed germinal vesicle (39%) or prometaphase I (22%). These results indicate that oocytes at metaphase I at and after sperm penetration are stimulated by sperm penetration to complete maturation. PMID- 1432977 TI - Long-term contraceptive efficacy of vaccine of ovine follicle-stimulating hormone in male bonnet monkeys (Macaca radiata). AB - A group of ten healthy fertile adult male bonnet monkeys were actively immunized using procedures acceptable for human use with pure follicle-stimulating hormone (oFSH) isolated from sheep pituitaries. The vaccine elicited an immunogenic response in all ten monkeys; the antibody-binding capacity, determined by Scatchard analysis, varied from 3 to 18 micrograms oFSH ml-1, the binding affinity ranging from 0.13 to 2.0 x 10(10) mol-1. A substantial population of antibodies against oFSH crossreacted with 125I-labelled human (h) FSH, used here as a representative ligand of primate FSH. The bioneutralization activity of the antisera assessed by a specific bioassay in vitro, when the antibody titre was high, was 6.9 +/- 0.18 micrograms hFSH ml-1. Immunization for 4.7-5.7 years did not affect the health and libido of the animals. Concentration of testosterone in serum remained normal throughout the study, but, within 150 days of immunization, there was a marked decrease (75-100%) in the number of spermatozoa in seminal ejaculates. Oligospermic status interspersed with azoospermia was maintained by periodic boosting. The fertility of these animals was monitored between 6 months and 2 years after primary immunization. All the ten animals proved infertile in repeated mating experiments with females of proven fertility. After stopping booster injections, nine of ten animals regained fertility, but the time taken for this depended upon the rate of decline of antibody titres. Re-boosting these monkeys with 100 micrograms oFSH after confirming that recovery had occurred revealed prompt increases in antibody titres followed once again by onset of oligo-azoospermia and infertility, underscoring the specificity of immunization effect. The immunized monkeys, apart from being acutely oligospermic, ejaculated spermatozoa that were markedly deficient in key acrosomal enzymes, such as acrosin and hyaluronidase, and motility as well as in their ability to penetrate a gel in vitro, suggesting that the infertility observed was due to gross reductions in the numbers of spermatozoa that could effectively interact with the oocyte and cause successful fertilization. PMID- 1432979 TI - Uterine surface temperature changes caused by electrosurgical endometrial coagulation. AB - To assess the risk for transmural thermal injury to abdominal viscera during electrosurgical ablation of the endometrium, thermocouples were laparoscopically directed to the surface of the uterus at the time of endometrial ablation. A 2- or 5-mm ball, or a barrel electrode directed through a urologic resectoscope was placed in the cornual area, and current varying from 50 to 150 W of unmodulated ("cutting") or modulated ("coag") current was applied for five seconds without moving the electrode. The resultant temperature rise of the uterine serosa did not exceed 6 degrees C. PMID- 1432978 TI - The contribution of singletons, twins and triplets to low birth weight, infant mortality and handicap in the United States. AB - Among multiple gestations the magnitude of neonatal mortality, morbidity and postneonatal handicap is unknown. Although the proportion of multiple births has risen dramatically during the past decade, the proportion of total births in the United States is relatively small. The vast majority of multiples are low birth weight (LBW) or very low birth weight (VLBW), conditions that magnify both short term and long-term risks. In this study, the risks for infant mortality and for postneonatal morbidity and handicap have been calculated from race-, plurality- and birth weight-specific mortality rates from the National Infant Mortality Surveillance (NIMS) Project and birth weight-specific postneonatal handicap rates from the Office of Technology Assessment report Healthy Children in proportion to the 1988 U.S. birth cohort. U.S. health objectives for the year 2000 for race specific birth weight and infant mortality rates were used for comparison. Compared with that of singletons, twins' and triplets' relative risks for LBW are 10.3 and 18.8, respectively. Their relative risks for VLBW are 9.6 and 32.7. Compared with singletons, twins and triplets have relative risks for infant mortality of 6.6 and 19.4, respectively. For twins and triplets, postneonatal survivors' relative risks for severe handicap are 1.7 and 2.9 while those for overall handicap are 1.4 and 2.0, respectively. Recommendations for optimizing pregnancy outcomes in multiple gestations include liberalized weight gains, reduced physical effort and early, comprehensive prenatal care. PMID- 1432980 TI - Pelviscopy/laparoscopy and its complications in Germany, 1949-1988. AB - The fourth German pelviscopy/laparoscopy statistical report includes survey data on a total of 219,314 laparoscopies from 354 clinics and 40,892 laparoscopies from 161 private practices. Clinics' response rate was 44.7%; 98.9% of them reported performing laparoscopies; and the number of serious complications requiring laparotomy or control laparoscopy was 492 (2.2/1,000). For private practices, the comparable figures were 66%, 90.8% and 123 (3/1,000), respectively. Compared with data from the third laparoscopy statistical survey, the data show a slight increase in serious complications, most of which were mechanical lesions of blood vessels in the abdominal wall or in the mesosalpinx, followed by mechanical lesions of the intestine. As shown by the previous survey, 16.5% of the complications were burns. For tubal sterilization, bipolar techniques were still predominant; approximately equal numbers of departments used this method, with or without subsequent transsection of the tubes. Endocoagulation by the method of Semm was the second most popular procedure; the use of clips and rings was of little significance. Monopolar high-frequency (HF) current was still used with transsection by 4.1% of clinics (4.7% of private practices) and without transsection by 2.5% (5.3%). Sterilization failure rates remained the same as those previously reported (4.6/1,000 in clinics, 5.3/1,000 in private practices); the highest rates were observed after the use of monopolar HF techniques. Sixty-six percent of the clinics and 41% of the private practices reported their intention to increase the use of endoscopic operational methods. PMID- 1432981 TI - Preoperative therapy in preparation for endometrial ablation. AB - In order to improve the success of endometrial ablation for uncontrolled uterine bleeding, a variety of preoperative agents were utilized. Patients were given either no preparation, progestins, danazol or leuprolide acetate depot as preoperative therapy to determine the best way to increase the incidence of amenorrhea and to decrease the failure rates. The lowest rates were achieved with danazol or no preparation, with amenorrhea rates of 41 and 43%, respectively. The highest rates were obtained with the use of either progestins or leuprolide acetate depot, 61 and 67%, respectively. Progestin use was discontinued early in the study because of side effects, resulting in numbers too low for accurate comparison. We concluded that the use of leuprolide acetate depot in a single dose regimen resulted in the highest amenorrhea rates, with minimal or no side effects. PMID- 1432982 TI - Endometrial ablation in women with abnormal uterine bleeding aged fifty and over. AB - Endometrial ablation, rapidly becoming a standard operation for the management of abnormal uterine bleeding, is usually performed for patients between ages 35 and 45. This study reports on the results of resectoscopic endometrial ablation for 26 patients aged 50 and older, followed from 7 to 43 months (average follow-up period, 21 months). Seventeen of the patients were menopausal at the time of the procedure or became menopausal during the follow-up period, with 13 on combined estrogen and progestin therapy and 4 on unopposed estrogen (because of progestin intolerance). Twenty-three of the 26 patients (88%) are amenorrheic, one premenopausal patient has normal periods and none have failed. The fear of hiding glandular tissue that subsequently becomes malignant is discussed and believed to be highly unlikely to occur. PMID- 1432983 TI - Sonographic assessment of late proliferative phase endometrium during ovulation induction. AB - Late proliferative phase endometrium was assessed sonographically in 400 patients undergoing ovulation monitoring or stimulation. Endometrial evaluation was classified in relation to its widest diameter (quantity) and by the presence or absence of a double-layered (outer echogenic/inner hypoechoic) pattern (quality). No patient conceived if the endometrium was totally echogenic and less than 8 mm in diameter. All patients who conceived had an endometrium that was double layered or greater than 9 mm in diameter. Positive, double-layered patterns correlated with correction of hormonal aberrations such as hypoestrogenism, hyperprolactinemia or hyperandrogenism. Such a positive pattern was also accomplished after discontinuation of clomiphene citrate in certain low-body weight/low-body fat women and administration of human menopausal gonadotropins to those patients. Application of the principles described to ensure the development of an adequate, double-layered (follicular phase) endometrium at midcycle were found to coincide with a higher incidence of pregnancy and viable gestation. PMID- 1432984 TI - Mechanical preparation of the endometrium prior to endometrial ablation. AB - Of 143 women who underwent endometrial ablation between May 1986 and August 1991, 16 also had repeat procedures. Medical preparation of the endometrial lining (danazol, leuprolide acetate, or nafarelin acetate) was used in 109 patients; mechanical preparation in the form of suction curettage, in 28 patients; and no preparation, in 6 postmenopausal patients. Evaluation of the results following endometrial ablation showed that the results in mechanically prepared patients were comparable to those in patients receiving traditional medical preparation; thus mechanical preparation can make the procedure simpler, enhance patient compliance, and reduce side effects considerably. PMID- 1432985 TI - Laparoscopic en bloc resection for treatment of the obliterated cul-de-sac in endometriosis. AB - In endometriosis patients with obliteration of the cul-de-sac, laparoscopic en block resection of the uterosacral ligaments, posterior cervix, cul-de-sac, and bowel wall efficiently removes invasive disease. PMID- 1432986 TI - Myomectomy after selective preoperative treatment with a gonadotropin releasing hormone analog. AB - In 1988 and 1989, 67 women (mean age, 36.7 years) underwent myomectomy to remove uterine fibroids; selection of the procedure was based on the presence of symptoms and the patient's desire to avoid hysterectomy. For 8 weeks before myomectomy, 48 patients with a uterine size greater than or equal to 16 weeks' gestation received the gonadotropin releasing hormone (GnRH) analog leuprolide acetate, 0.5 mg self-administered daily by subcutaneous injection or 3.75 mg as the depot form every 28 days by intramuscular injection; the remaining 19 patients were used for a comparison. In the leuprolide-treated patients, the mean uterine size and mean number of fibroids removed per patient were significantly higher, and the mean postoperative hemoglobin concentration was significantly lower than in the non-leuprolide-treated group. The mean estimated blood loss and mean length of hospital stay were equivalent for the two groups. Eight patients (12%), all but one in the leuprolide-treated group, developed postoperative complications, primarily infections that were treated successfully with antibiotics; one patient, the only one undergoing a repeat myomectomy, experienced pelvic hematoma, infection and pelvic thrombophlebitis. There were no significant adverse reactions attributable to leuprolide administration. PMID- 1432988 TI - Intracervical prostaglandin E2 gel. Safety for outpatient cervical ripening before induction of labor. AB - Cervical ripening prior to induction of labor is often necessary for medical complications of pregnancy. We proposed to prospectively determine the safety of administering prostaglandin E2 (PGE2) gel intracervically in an outpatient setting. Four hundred forty-six patients underwent 515 gel procedures as outpatients. Trained perinatal nurses placed 0.5 mg of PGE2, prepared in a standard methylcellulose base, in the intracervical canal. The PGE2 dose was administered every two hours for a total of three doses if labor did not start. The patient was sent home two hours after the last dose if she was not in active labor. Labor started in 90 patients (20%) during the gel procedure; they were admitted to the labor-and-delivery unit. The remaining patients were discharged. Eighty-eight patients (20%) were later admitted in active labor prior to scheduled induction. One patient (0.02%) was found to have occasional prolonged decelerations on admission and underwent a cesarean section two hours after admission; the Apgar scores were 8 and 9 and the arterial pH, 7.21. Hyperstimulation with excessive intrauterine activity caused significant deceleration of the fetal heart rate in four patients (0.8%), two of whom required transfer to the labor-and-delivery unit but none of whom needed a cesarean section for fetal distress. PGE2 gel can be administered safely intracervically as an outpatient procedure by trained perinatal nurses. PMID- 1432987 TI - Calcium requirements and the diets of women and children. A review of dairy resources. AB - This review concerns the role of calcium in nutrition and health and its relation to the changing American diet. The ideal dietary calcium intakes for women and children represent the United States Department of Agriculture's most recent recommended dietary allowances. Both calcium and total nutrient composition of cow, goat and human milk differ. Goat milk has special utility in the treatment of childhood allergy. PMID- 1432989 TI - Significance of intrapartum amniotic fluid volume in the presence of nuchal cords. AB - Among 70 women delivering infants with nuchal cords, there was a significantly higher incidence of meconium passage and severe variable fetal heart rate decelerations/fetal bradycardia in those who had intrapartum oligohydramnios, as defined by an amniotic fluid index less than or equal to 5.0 cm. Oligohydramnios in the presence of nuchal cord entanglement might represent an increased risk of ominous intrapartum fetal heart rate patterns. PMID- 1432990 TI - 3 alpha-Androstanediol and 3 alpha-androstanediol glucuronide. Maternal and umbilical cord plasma concentrations in normal pregnancy. AB - Concentrations of 3 alpha-androstanediol (A) and 3 alpha-androstanediol glucuronide (AG) were measured with a radioimmunoassay in pregnancy plasma samples collected from the mother in the first trimester (first, n = 18) and second trimester (second, n = 20) and at term (n = 14). At term, along with the maternal samples, matching cord plasma samples were also obtained (n = 14). Throughout pregnancy the levels of A and AG were significantly higher than in normally menstruating women. Although the total concentration of A and AG did not change significantly throughout pregnancy, the levels of A in the second and at term were significantly higher than in the first. In contrast, AG concentrations in the second were significantly lower than in the first and at term. As compared to the maternal concentrations at term, the cord levels of AG and A plus AG were not significantly different. However, the levels of A in the cord were significantly lower than those in the maternal circulation at term. Significant correlations were observed between the term maternal and cord levels of AG and A plus AG. No sex-related differences in the plasma levels of A and AG were noted. The results show that levels of A and AG increase significantly in the first trimester and remain elevated throughout pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1432991 TI - Influence of triphasic oral contraceptives on blood rheology and hemostatic and metabolic patterns in young women. Results of a three-year study. AB - Long-term (three-year) variations in clinical, hemorheologic, hemostatic and blood lipid parameters were evaluated in 20 young healthy women taking a triphasic oral contraceptive. Body weight, arterial blood pressure, whole blood, plasma and serum viscosity, erythrocyte deformability, fibrinogen, fibronectin, alpha-2 macroglobulin, Von Willebrand factor antigen, triglycerides, nonesterified fatty acids, total and low density lipoprotein cholesterol, very low density lipoprotein, low density lipoprotein and apolipoprotein B levels remained unchanged throughout the study. However, high density lipoprotein cholesterol, high density lipoprotein and apolipoprotein A1 serum concentrations increased significantly during treatment. Long-term use of the triphasic oral contraceptive does not seem to adversely affect the blood rheology pattern or vascular endothelium function, which are the main factors responsible for the development of thromboembolic complications. PMID- 1432992 TI - Maternal coagulation inhibitors and the effects of cesarean delivery. AB - Maternal hypercoagulability in normal pregnancy results from significant increases in blood factors that promote thrombosis or decreases in factors that inhibit thrombosis, such as antithrombin III (AT-III) and proteins C and S. The precise role of these factors in puerperal hemostasis is not clear. In 10 normal, pregnant women at term undergoing scheduled repeat cesarean section, the percent activities of AT-III, proteins C and S, and C4b-binding protein were determined in peripheral venous blood preoperatively and in samples of uterine venous blood before the uterine incision was made and 5 and 15 minutes after placental delivery using the Laurell Rocket electroimmunodiffusion technique. The mean percent activities of AT-III (73%), protein S (81%) and C4b-binding protein (85%) were lower than those in nonpregnant controls, were similar in peripheral and uterine venous blood and were unchanged after placental delivery. These data suggest that such factors may not play an important role in acute uteroplacental hemostasis during normal pregnancy. PMID- 1432993 TI - Characteristics of indigent women with ruptured and unruptured tubal pregnancies. AB - The diagnosis of tubal pregnancy, whether ruptured or unruptured, often requires a surgical procedure, such as laparoscopy or laparotomy, for confirmation. We compared women with ruptured and unruptured tubal pregnancies to determine whether the clinical presentations, morbidity and surgical complications in the two groups were significantly different. We compared the demographic characteristics, clinical presentations, laboratory findings, morbidity and complications from surgical management in the two groups. Women with ruptured tubal pregnancies had a higher incidence of abdominal pain lasting less than 24 hours, adnexal tenderness and positive culdocentesis from hemoperitoneum as compared to women with unruptured tubal gestations. Abnormal uterine bleeding was observed less frequently in women with ruptured tubal pregnancies as compared to women with unruptured ones despite similar gestational ages at presentation. All the patients with a tubal pregnancy were managed surgically. The morbidity and surgical complication rates in the two groups were not significantly different. PMID- 1432994 TI - Persistence of a normal pregnancy after an early luteectomy. A report of two cases. AB - Two cases occurred of early luteectomy/left cystectomy. In one case it resulted from a hemorrhagic corpus luteum at four weeks' gestation. In the second case it resulted from a left adnexectomy at five weeks from torsion of the adnexa. Histologic analysis defined the lesions as a hemorrhagic corpus luteum and necrotic ovary, respectively. Despite the lack of a corpus luteum and the absence of hormonal replacement therapy, both pregnancies developed normally, in the first case for 7 weeks, until it was terminated on the patient's request, and in the second case until 38 weeks, when a normal infant was delivered by cesarean section. PMID- 1432995 TI - Type II congenital cystic adenomatoid malformation of the lung with a mediastinal shift. A case report. AB - We report a case of an early (22-week) prenatal diagnosis of type II congenital cystic adenomatoid malformation of the lung complicated by a mediastinal shift. Detailed ultrasound examination of the fetus, including fetal Doppler velocimetry and echocardiography, and diagnostic amniocentesis were normal. There was a gradual, spontaneous resolution of the mediastinal shift and improvement in the lung lesions. The intrapartum and early neonatal clinical courses were uneventful. PMID- 1432996 TI - T cell targetted immunotherapy with monoclonal antibodies in rheumatoid arthritis. PMID- 1432997 TI - Does prolactin have a role in the pathogenesis of systemic lupus erythematosus? PMID- 1432998 TI - Pristane induced arthritis in mice. IV. Immunotherapy with monoclonal antibodies directed against lymphocyte subsets. AB - Pristane induced arthritis (PIA), a seropositive experimental disease model in mice, was used to investigate the influence of immunotherapy with monoclonal antibodies against lymphocyte subsets. Treatment with L3T4, a monoclonal antibody specific for murine CD4+ T cells, significantly reduced the incidence of pristane arthritis, and delayed the disease onset. Monoclonal antibody to Lyt2, the murine CD8+ T cell marker, significantly reduced the levels of rheumatoid factor in pristane injected animals compared with controls, but did not influence the clinical course of PIA. Our experiments demonstrate the ability of anti-CD4 antibodies to modify the course of PIA, and provide support for the hypothesis that CD4+ T lymphocytes have an important role in the pathogenesis of this experimental autoimmune arthritis. PMID- 1432999 TI - Cyclosporine and chloroquine synergistically inhibit the interferon-gamma production by CD4 positive and CD8 positive synovial T cell clones derived from a patient with rheumatoid arthritis. AB - OBJECTIVE: To investigate synergistic interaction between cyclosporine (Cy) and chloroquine (Chl) in an in vitro system, with regard to interferon-gamma (IFN) production by OKT3 activated T cell clones. METHODS: CD4+ and CD8+ T cell clones, derived from synovial tissue of a patient with rheumatoid arthritis (RA) were activated with plastic coated OKT3 monoclonal antibody in the presence or absence of various concentrations of Cy, Chl and their combinations. After 24 h of incubation the supernatants were assayed for IFN by ELISA: RESULTS: Cy as well as Chl were able to completely inhibit in a concentration dependent fashion the IFN production by CD4+ and CD8+ T cell clones. Combinations of Cy and Chl, which in themselves give minor inhibition of IFN production, were able to inhibit in a synergistically enhanced fashion the production of IFN by these clones. The synergy was formally proven by the construction of isoboles. This synergy was most pronounced when drug concentrations were used which individually gave minor inhibition of IFN production. CONCLUSION: We conclude that the results of our in vitro experiments may give rise to further investigation of the promising combination of Cy and Chl in the treatment of RA. PMID- 1433000 TI - Cyclosporine A for the treatment of necrotizing scleritis and corneal melting in patients with rheumatoid arthritis. AB - Two of the ocular complications of rheumatoid arthritis (RA), necrotizing scleritis and keratolysis, have been associated with poor response to standard ocular therapy, and thus poor ocular outcome. We describe 6 patients with active ocular disease and active RA who failed to respond to disease modifying agents or immunosuppressive therapy and whose ocular and arthritic disease subsequently responded to cyclosporine A. Drug related complications were consistent with those reported for patients receiving similar doses for RA. PMID- 1433001 TI - Interleukin 2 receptor membrane bound and in soluble form in the aqueous humor and peripheral blood of patients with acute untreated uveitis. AB - Uveitis is a manifestation of various chronic inflammatory arthritic conditions. There are considerable data implicating abnormalities of immune function in the etiopathogenesis of uveitis. We evaluated the percentage of cells expressing interleukin 2 (IL-2) receptor (membrane bound) and the levels of soluble IL-2 in the blood and aqueous humor of patients in various rheumatic diseases and acute untreated uveitis. Our findings showed increased IL-2 receptors (IL-2R) and soluble IL-2 receptors on the aqueous humor of patients with uveitis when compared to healthy controls. These results suggest an immunoregulatory role of IL-2R in acute uveitis and raises the possibility that its detection may be useful in management. PMID- 1433002 TI - Recurrence of cervical spine instability in rheumatoid arthritis following previous fusion: can disease progression be prevented by early surgery? AB - In a retrospective study, 110 patients with rheumatoid arthritis who had cervical spine fusion were evaluated for recurrence of cervical spine instability and resultant need for further surgery. Recurrence of cervical instability was correlated with initial radiographic abnormality, primary surgical procedure and interval between the 2 surgeries. There were 55 patients who had atlantoaxial subluxation (AAS) and required C1-C2 fusion as primary surgery. Three of these patients (5.5%) developed subaxial subluxation (SAS) and had a second procedure after a mean interval of 9 years. Twenty-two patients had AAS with superior migration of the odontoid (AAS-SMO) and had initial surgery of occiput-C3 fusion. Eight of these patients (36%) developed SAS and had a second surgery after a mean interval of 2.6 years. Of the 19 patients with primary radiographic deformity of SAS, one required further surgery for subluxation of an adjacent superior vertebra after a period of 6 years. Fourteen patients had combined deformity of AAS-SMO-SAS, and one required further surgery for SAS after an interval of 22 months. Recurrence of cervical instability following a previous fusion occurred in 15% of these 110 patients. It was seen in 5.5% of patients with initial deformity of AAS vs 36% of patients with AAS-SMO. No patients with C1-C2 fusion for AAS progressed to develop superior migration of the odontoid. We conclude that early C1-C2 fusion for AAS before development of SMO decreases the risk of further progression of cervical spine instability. The pattern of progression of cervical spine involvement, as discussed in the literature, is reviewed. PMID- 1433003 TI - 99mTc human immunoglobulin scintigraphy--a reliable method to detect joint activity in rheumatoid arthritis. AB - The ability of 99mtechnetium labelled nonspecific, polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to depict and quantify synovial inflammation was studied in 30 patients with rheumatoid arthritis (RA). All patients were injected with 350 MBq 99mTc-IgG and imaging was performed 4 h later. This resulted in excellent images of inflamed synovium. Scores for 99mTc IgG joint scintigraphy correlated highly with scores for joint swelling and C reactive protein levels, weakly with pain scores and not with radiographic scores of joint destruction. These results suggest that 99mTc-IgG joint scintigraphy may provide an objective test to detect synovitis and measure the activity of the disease. PMID- 1433005 TI - Anti-dsDNA antibodies in laboratory workers handling blood from patients with systemic lupus erythematosus. AB - The presence of antinuclear antibodies was determined in female laboratory workers with varying degrees of exposure to blood from patients with systemic lupus erythematosus (SLE). Subjects recruited from SLE research laboratories and a membership roster provided by the American Society for Medical Technology were classified according to self-reported frequency of handling blood from patients with SLE into high and low exposure groups. Employment and medical history were obtained by questionnaire from each study subject and their sera were tested for antibodies to double stranded DNA, single stranded DNA, and synthetic polynucleotide poly(dA-dC).poly(dG-dT) by ELISA. Analysis of the results using an independent t test showed the mean optical density for anti-dsDNA was higher in the high exposure group (mean = 0.010) than in the low exposure group (mean = 0.005, p = 0.016). There were no significant differences found between the 2 groups for anti-ssDNA or anti-poly(dA-dC).poly(dG-dT), but the means for both anti-dsDNA and anti-poly(dA-dC).poly(dG-dT) were higher in the laboratory workers than in an unexposed nonlaboratory group of women (p less than 0.001). Our results are provocative for they lend support to the hypothesis that a transmissible agent capable of causing autoantibody formation may exist in blood from patients with SLE. PMID- 1433004 TI - Antinuclear antibodies heralding the onset of systemic lupus erythematosus. AB - On the basis of record linkage with the Social Security Institution's population register, 16 specimens from healthy subjects who subsequently developed systemic lupus erythematosus or mixed connective tissue disease could be traced from stored sera collected in connection with nationwide maternity welfare program in Finland. The sera were tested for antinuclear antibodies (ANA) using an immunofluorescence technique. Ten of the 16 specimens were positive. Eight of 11 cases were positive when the interval from taking the blood specimen to the onset of the first symptoms of disease was 2 years or less and 2 of 5 cases were positive when the interval was over 3 years. Eighteen of 21 sera with established disease and 5 of 85 control sera from the same serum collection were positive. Thus, ANA as detected by a sensitive technique frequently precede the onset of disease indicating that they are not a secondary manifestation of inflammation or tissue destruction. PMID- 1433006 TI - Light microscopy of dried saliva in the evaluation of xerostomia of the sicca syndrome. A preliminary report. AB - Dried, freshly produced saliva from 21 patients with xerostomia related to the sicca syndrome [15 with primary Sjogren's syndrome (pSS), 3 with rheumatoid arthritis (RA) and secondary Sjogren's syndrome (sSS), and 3 with Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE)] and 21 age and sex matched controls, was examined by light microscopy. A typical fern-like pattern was demonstrated by the crystallized mucus of the healthy individuals. In contrast, much thicker, shorter, irregular and densely arranged branches of crystallized mucus, sometimes giving a reindeer horn appearance, were observed in the patients' saliva. Given the lack of a reliable clinical measure for the objective evaluation of xerostomia, light salivary microscopy, simple and easy as it is, may fill this deficit, if its sensitivity and specificity are documented. PMID- 1433007 TI - A family study of the antiphospholipid syndrome associated with other autoimmune diseases. AB - Antiphospholipid syndrome (APS) is an entity characterized by recurrent thrombotic events and may occur spontaneously or in the context of systemic lupus erythematosus (SLE). We describe an English Canadian family in whom the propositus, a woman with Graves' disease and SLE, was found to have a lupus anticoagulant and anticardiolipin antibody (aCL). A brother with deep vein thrombosis, pulmonary emboli, bilateral adrenal hemorrhage and thrombocytopenia, circulating anticoagulant and aCL had a positive antinuclear antibody and Coombs' test, but no other features of SLE. Fourteen members of 3 generations of this family underwent clinical assessments, serological testing and HLA typing. The propositus' mother had a family history of autoimmune thyroid disease and the father had aCL, but was asymptomatic. The thyroid disease and the SLE were associated with HLA-B8, DR3 haplotype. The aCL and the anticoagulant were associated with HLA-B60, DR4 haplotype. Both these haplotypes were present in the propositus. Among the other 4 carriers of the haplotype B60, DR4, 3 demonstrated significant titers of aCL. Our findings support the reported association between APS and the HLA haplotype DR4 in patients of English descent with SLE. PMID- 1433008 TI - Antiphospholipid antibodies require beta 2-glycoprotein I (apolipoprotein H) as cofactor. AB - IgG was isolated from 9 patients with high levels of anticardiolipin antibodies (aCL). The standard ELISA was modified, using gelatin to postcoat ELISA plates and as diluent. Under these conditions, 8/9 samples of IgG bound to cardiolipin only in the presence of a cofactor, found in fetal calf serum and normal human serum (NHS). beta 2-glycoprotein I (apolipoprotein H) was at least as effective as NHS as a cofactor for 7/9 IgG samples. Our studies confirm that for some aCL detected in conventional assays, the antibody will react with cardiolipin only if beta 2-glycoprotein I is present. PMID- 1433009 TI - Color chart assisted diagnosis of Raynaud's phenomenon in an unselected hospital employee population. AB - The prevalence of Raynaud's phenomenon (RP) in 750 subjects was assessed by questionnaire, clinical interview, and use of a chart of color photographs taken of hands during attacks of RP. Eighty-three of 600 women (13.8%) and 7 of 150 men (4.7%) reported cold induced digital color changes on the questionnaire, 76 women (12.7%) and 6 men (4%) were diagnosed as having RP at an independent clinical interview, and 3 women could not be assessed using the color chart because of defective color perception. Fifty-four of the remaining 597 women (9%) and 6 of 150 men (4%) were diagnosed as having RP when a positive response to both chart and questionnaire was required. The color chart should be useful in lessening the frequency of false-positive responses and in standardizing the diagnosis for epidemiological surveys. PMID- 1433010 TI - Tuberculous arthritis in the course of connective tissue disease: report of 4 cases. AB - We describe 4 female patients with diverse connective tissue diseases who developed tuberculous arthritis concurrently with their underlying disease, in the absence of lung involvement. Throughout, diagnosis was delayed but later confirmed by detection of Mycobacterium tuberculosis in synovial membrane culture. Two patients died of unrelated causes, while the other 2 recovered with chronic joint sequelae. Despite the rarity of this association, M. tuberculosis infection should be considered in the differential diagnosis of chronic mono or oligoarthritis in patients with connective tissue diseases. PMID- 1433011 TI - Hyperferritinemia in adult onset Still's disease and the hemophagocytic syndrome. AB - Increments in serum ferritin levels in adult onset Still's disease (AOSD) were reported to be higher than one could expect for a simple inflammatory state. When we analyzed the scores of 40 patients with various severe inflammatory diseases aside from AOSD, we recorded no serum ferritin values higher than 3,300 ng/ml (N less than 200 ng/ml). In 3 of 10 consecutive patients with AOSD, the ferritin levels were higher than 3,500. Among these 3 patients, one case had a ferritin value of 3,600 ng/ml and bone marrow aspirate showed a marked hyperplasia of mature appearing histiocytes, and the 2 other patients (serum ferritin levels of 65,000 ng/ml and 250,000 ng/ml) displayed the features of a hemophagocytic syndrome. In 2 patients with normal or mildly increased levels of ferritin, the bone marrow examination was normal. We suggest that very high serum ferritin levels encountered in AOSD reflect the presence of histiocytic hyperactivity that sometimes leads to a hemophagocytic syndrome. PMID- 1433012 TI - Biochemical clues to a fibromyalgia-depression link: imipramine binding in patients with fibromyalgia or depression and in healthy controls. AB - Both fibromyalgia and depression may be related to disturbed serotonin metabolism, and an association between the 2 disorders has been postulated. We measured 3H-imipramine binding (IB), a biochemical indicator of serotonin uptake, pretreatment, in 10 nondepressed women with fibromyalgia, 14 subjects with major depression, and 10 volunteer controls. Our objective was to determine if IB in the 2 patient groups differed and in the same direction from the control values. Compared with depressed women, IB was significantly lower both in the women with fibromyalgia and in the men with depression. However, no women with fibromyalgia or men with depression had IB levels that were significantly different from control women and men. There was a trend for higher IB levels in depressed compared to control women. PMID- 1433013 TI - Effects of tiaprofenic acid and acetylsalicylic acid on human articular chondrocytes in 3-dimensional culture. AB - Two nonsteroidal antiinflammatory drugs (NSAID: acetylsalicylic acid, ASA, and tiaprofenic acid, TA) were tested on differentiated human chondrocytes cultivated in clusters. DNA synthesis was depressed by ASA at therapeutic concentrations. The amount of proteoglycans in culture medium was decreased by ASA, whereas type II collagen was not modified. By contrast, TA did not affect chondroformative processes in chondrocytes. Both NSAID were potent inhibitors of prostaglandin E2 (PGE2) synthesis, TA being more efficient than ASA. From these experiments, we conclude that TA and ASA inhibit PGE2 synthesis; TA did not depress chondroformative variables in human cartilage in vitro, while ASA induced a decrease of DNA and proteoglycan syntheses. PMID- 1433014 TI - Fibronectin fragments in osteoarthritic synovial fluid. AB - Fibronectin is an adhesive multifunctional glycoprotein found in the extracellular matrix of most types of cells and that exerts growth factor, differentiative and chemotactic activities toward many types of cells, including those cells found in knee joint tissue. Since fibronectin levels in the synovial fluid (SF) and on the cartilage surface of patients with osteoarthritis (OA) have been shown to be greatly increased over normal levels and since protease levels are also enhanced in diseased cartilage, we have investigated the presence of fibronectin fragments in the SF of patients with OA. We report that concentrations of at least 1 microM of 100 to 200 kDa fragments were found in all OA fluids examined. Since we have recently shown that fibronectin fragments can cause cartilage to release metalloproteinases, resulting in severe proteoglycan depletion, and others have shown that fragments also enhance metalloproteinase expression in synovial fibroblasts, the presence of these fragments suggests pathologic consequences in arthritis. PMID- 1433015 TI - Comparison of the acute inflammation induced by calcium pyrophosphate dihydrate, apatite and mixed crystals in the rat air pouch model of a synovial space. AB - Pure monoclinic or triclinic calcium pyrophosphate dihydrate (CPPD) crystals, apatite crystals or mixtures of these crystals were injected into the synovial like space created by the rat air pouch to compare the acute inflammation induced by these crystals. Fluids were withdrawn 6 h after injection and examined for leukocyte counts, protease, prostaglandin E2 (PGE2) and tumor necrosis factor (TNF) levels. CPPD crystals (especially monoclinic CPPD) induced higher numbers of leukocytes, and more protease, PGE2 and TNF than apatite. CPPD seemed to play a predominant role in the acute inflammation induced by mixed crystals. PMID- 1433016 TI - The philatelic rheumatologist. AB - Many postage stamps illustrate themes, persons, or topics with rheumatologic connections. Examples include scientists from related disciplines, victims of rheumatic diseases, drugs used for arthritis, and stamps commemorating events such as World Rheumatism Year. A brief orientation to postage stamps and philately is given, and a small collection of rheumatologically related stamps is illustrated. PMID- 1433017 TI - Association of methotrexate, rheumatoid arthritis and lymphoma: report of 2 cases and literature review. AB - We describe 2 Caucasian men with rheumatoid arthritis (RA) who developed non Hodgkin's lymphoma of identical histological type during treatment with low dose oral weekly methotrexate (MTX). Both patients had longstanding RA and had been treated with MTX for over 2 years at time of tumor diagnosis; neither had secondary Sjogren's syndrome. The oncogenic potential of MTX and RA arthritis is reviewed. PMID- 1433018 TI - Massive intrahepatic hemorrhage following routine liver biopsy in a patient with rheumatoid arthritis treated with methotrexate. AB - Massive intrahepatic hemorrhage occurred in a patient with rheumatoid arthritis (RA) after a routine liver biopsy done to assess possible methotrexate (MTX) hepatotoxicity. Major complications of liver biopsy occur about once in every 600 biopsies, and mortality from liver biopsy has been reported. Life threatening hepatic toxicity occurs rarely during low dose MTX administration, and it is unclear whether routine liver biopsies identify patients at high risk for these complications. Until the relative risks of liver biopsy and serious MTX liver toxicity are better defined, the use of routine liver biopsies should be recommended only after careful consideration of potential procedural complications in patients with RA treated with MTX. PMID- 1433019 TI - Thrombotic thrombocytopenic purpura complicating systemic lupus erythematosus. Case report and literature review from the plasmapheresis era. AB - Although thrombotic thrombocytopenic purpura (TTP) has been described in patients with systemic lupus erythematosus (SLE), the relationship between these 2 diseases is controversial. We recently treated a patient with longstanding SLE who developed TTP. The patient responded to therapy with aggressive plasmapheresis. Review of the literature revealed that TTP may occur in the setting of either active or inactive SLE. Survival in SLE associated TTP correlated with the use of plasma therapy (plasma infusion or plasmapheresis) rather than with the activity of the underlying autoimmune disease. We conclude that TTP and SLE represent distinct clinical entities that may occur together in an immunologically predisposed host. The use of plasma therapy appears to have had a significant impact on survival in these patients. PMID- 1433021 TI - Seven Achilles tendinitis including 3 complicated by rupture during fluoroquinolone therapy. AB - We describe 7 Achilles tendinitis occurring during fluoroquinolone treatment. Antibiotic agents used were pefloxacin and ofloxacin. In 3 cases the course was complicated by rupture of the tendon, one of which is histologically documented. The toxic effects of quinolones on tendon is discussed. PMID- 1433020 TI - Thrombotic thrombocytopenic purpura in systemic lupus erythematosus and antiphospholipid antibodies: effective treatment with plasma exchange and immunosuppression. AB - We describe 2 patients with systemic lupus erythematosus (SLE) with neurological complications and thrombocytopenia, who, upon further investigation, were found to have thrombotic thrombocytopenic purpura. While neither patient responded to treatment with corticosteroids, both responded to plasma exchange and intravenous cyclophosphamide. This highlights the need to carefully consider this diagnosis in patients with SLE presenting with neurological complications and thrombocytopenia. PMID- 1433022 TI - Cerebral aneurysm in relapsing polychondritis. AB - A 51-year-old woman with relapsing polychondritis involving auricular and nasal cartilage, hearing loss, vasculitic skin lesions and a cerebral aneurysm of the posterior cerebral artery is described. Cerebral aneurysm is a rare manifestation of relapsing polychondritis which to our knowledge has not yet been described. PMID- 1433023 TI - Recurrent episodes of pseudoseptic arthritis in rheumatoid arthritis: response to D-penicillamine and methotrexate. PMID- 1433024 TI - The coexistence of classic RA and AIDS. PMID- 1433025 TI - Nailfold capillary density as a possible indicator of pulmonary capillary loss in SLE but not in mixed connective tissue disease. PMID- 1433026 TI - Intravenous methylprednisolone pulse therapy in Still's disease. PMID- 1433027 TI - Arthritis mutilans associated with cutaneous T cell lymphoma. PMID- 1433028 TI - Wegener's legacy. PMID- 1433029 TI - Familial Mediterranean fever in children. PMID- 1433030 TI - Amyloidosis in pediatric rheumatic diseases. PMID- 1433031 TI - Lightning and electrical injury. PMID- 1433032 TI - The challenge of unexplained diseases: migraine. PMID- 1433033 TI - Of ethics and education: strategies for curriculum development. PMID- 1433034 TI - The two faces of medical education: Flexner and Osler revisited. PMID- 1433035 TI - Endotracheal intubation skills of medical students. AB - The ability and confidence of clinical medical students to insert endotracheal tubes correctly and quickly and to recognize oesophageal misplacement was evaluated. Ten (33%) of the medical students intubated the trachea correctly at their first attempt but 14 (47%) incorrectly identified the position of the endotracheal tube. However, recognition improved by their second and third attempts (70% and 80% respectively). Ninety-three percent of students intubated correctly on their third attempt. Although medical students can obtain better results at correct tube placement with repeated attempts under optimum conditions -a practice effect--and do better at recognizing correct tube placement there is still a persistent failure to recognize endotracheal tube misplacement, ie oesophageal intubation. It is the ability to recognize oesophageal intubation promptly that is a life-saving skill. This essential skill should be taught during the introductory anaesthesia programme through the use of clinical patients. PMID- 1433036 TI - Emotional distress in doctors: sources, effects and help sought. AB - All doctors in a London Teaching Hospital were sent a self-administered, anonymous questionnaire, to study past episodes of emotional distress. We inquired about frequency of past and current emotional distress, sources of distress, effects on work and home life, type of help sought and perceived outcome of that help. Of 320 doctors, 210 (66%) responded. One hundred and forty one (68%) reported previous episodes of moderate or severe emotional distress. Logistic regression revealed that distress was significantly more common in younger doctors and in women. Many respondents reported work problems as causing their distress and work was frequently adversely affected by episodes of distress. Professional help was rarely sought; non-professional help was from family and friends. Current emotional distress was related to a history of past distress, especially among the most junior doctors. We conclude that past emotional distress is reported by most doctors, with work pressures an important contributing factor. Doctors do not appear to use available sources of professional help. Our findings confirm that doctors have difficulty disclosing psychological problems. Specific programmes aimed at prevention and management of distress in doctors need to be initiated and evaluated. PMID- 1433038 TI - A pilot study of the effect upon multiple sclerosis of the menopause, hormone replacement therapy and the menstrual cycle. AB - A questionnaire enquiring about changes in severity of symptoms of multiple sclerosis with the menstrual cycle, menopause and use of hormone replacement therapy was answered retrospectively by 11 premenopausal and 19 postmenopausal women. Eighty-two per cent of menopausal women reported an increase in severity premenstrually. Of the postmenopausal women 54% reported a worsening of symptoms with the menopause, and 75% of those who had tried hormone replacement therapy reported an improvement. The results of this pilot study indicate the need for further research to clarify the effects of the menopause and hormone replacement therapy upon multiple sclerosis. PMID- 1433037 TI - Sudden death in epilepsy: an avoidable outcome? AB - In a retrospective survey of mortality among the first 1000 unselected patients referred to the Epilepsy Research Unit at the Western Infirmary in Glasgow between 1985 and 1990, a total of 18 deaths were identified. Three patients had committed suicide and one each had died of status epilepticus in hospital, a subdural haematoma and a myocardial infarction. The remaining 12 deaths (67%) were sudden (median age 32 years; range 22-68 years). Poor seizure control and poor compliance with antiepileptic drug therapy were recorded in only three (25%) of these patients. There was a change in antiepileptic drug regimen in five (28%) in the month before death. Only two (17%) underwent postmortem examination. In nine of the 12 patients dying suddenly, the primary cause of death was not listed as epilepsy but as asphyxia (3), aspiration (2) and one each of ischaemic heart disease, myocardial infarction, asystole and drowning (in the bath). 'Status epilepticus' was assumed to have been responsible for the other three deaths, two of which were unwitnessed. Sudden death in people with epilepsy is an entity of great concern. Appropriate death certification and mandatory postmortem examination are essential to provide a truer picture of this neglected phenomenon. PMID- 1433039 TI - Eye tests in the elderly: factors associated with attendance and diagnostic yield in non-attenders. AB - Patients aged 60-75 years registered with one inner city general practice were sent a questionnaire asking when they last received an eye check by an optometrist. Of the 193 (77%) who responded, 110 (59%) had attended in the last 2 years, and 138 (74%) in the last 3 years. Males and those with mobility problems were less likely to have had their eyes checked. Seventy-seven previous non attenders were offered an appointment with an optometrist and this was accepted by 34 (44%). These individuals showed a high level of ophthalmic morbidity. Discussion of optometric checks should be included in general practice health checks and the elderly surveillance programme. PMID- 1433040 TI - Beyond music: auditory temporary threshold shift in rock musicians after a heavy metal concert. AB - Audiometry was undertaken before and within half an hour following a heavy metal concert to assess evidence of noise damage. Of the four members tested, one member wore an ear defender in his right ear during the period of noise exposure. All unprotected ears showed a temporary threshold shift which was maximum in the lower frequencies. There was some evidence that early noise damage had occurred with a dip at 6 kHz. The role of music as noise and its potential to damage the cochlea are discussed. PMID- 1433041 TI - Hypnoanalgesia for chronic pain: the response to multiple inductions at one session and to separate single inductions. AB - Serial hypnotic inductions conveying the same analgesic message produce a progressively longer response in an increasing number of patients. The resulting analgesia appears to be independent of the spacing of inductions--whether given at a single session or on separate occasions--and to depend upon their number. However, multiple inductions at a single session save time. Elimination of pain can be achieved, by either approach, for a year or more in up to 70% of patients. PMID- 1433042 TI - Diagnosis and management of renal angioma. AB - Five patients with symptomatic renal angiomata are described. All presented with heavy haematuria and unilateral ureteric obstruction without evidence of a mass distorting the renal architecture. Renal angiomata are most easily diagnosed by selective renal angiography. They may be treated by intraarterial embolization, avoiding the need for major ablative surgery. PMID- 1433043 TI - Europe and the tropics--how benevolence can lead to disaster. PMID- 1433044 TI - The speech defect of Moses. PMID- 1433045 TI - Pseudocyst or tumour? An amylase-producing leiomyosarcoma. PMID- 1433046 TI - Oesophago-gastrectomy for Marie-Bamberger syndrome. PMID- 1433047 TI - Lienocolonic fistula following splenic abscess. PMID- 1433048 TI - Central lumbar disc prolapse following chiropractic manipulation: a call for audit of 'alternative practice'. PMID- 1433049 TI - Serum sickness and purpura following intravenous streptokinase. PMID- 1433050 TI - Partial cardiopulmonary bypass for the treatment of profound accidental hypothermic circulatory collapse. PMID- 1433051 TI - Cerebral abscess due to Clostridium septicum. PMID- 1433052 TI - Cardiac injury and electrocution. PMID- 1433053 TI - Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. PMID- 1433054 TI - Helping the police with their enquiries. PMID- 1433055 TI - The aging driver. PMID- 1433056 TI - The measurement of fatigue and chronic fatigue syndrome. PMID- 1433057 TI - Diurnal changes in perceptions of energy and mood. AB - Data from five separate groups of volunteers show that diurnal variation in perceptions of physical and mental energy ('vigour') can be simply measured by the use of visual analogue scales. In all five groups, perceptions of vigour were significantly higher in the morning than at other times of day. In three groups where energy levels were measured six times daily the values achieved between 10.00 h and 12.00 h were significantly higher (P < 0.05) than those recorded on rising or retiring. Some evidence was also found for the existence of high energy levels in the evening (particularly among the undergraduates) and for an 'afternoon dip' in energy in about 20% of subjects. Higher levels of positive affect were also found in the morning and levels recorded between 10.00 h and 12.00 h were significantly greater than those on rising or retiring, (P < 0.01). However, no similar diurnal variation was observed for negative affect. The difference may be due to the fact that positive affect has a distinct 'biological' component contributing to perceptions of energy, whilst negative affect depends more on features in the individual's environment, which show no consistent diurnal pattern. PMID- 1433058 TI - Dementia and driving. AB - Many European countries test cars, but not their drivers, as they age. There is evidence to suggest that human factors are more important than vehicular factors as causes of motor crashes. The elderly also are involved in more accidents per distance travelled than middle-aged drivers. As the UK relies on self certification of health by drivers over the age of 70 years, we examined the driving practices of patients with dementia attending a Memory Clinic. Nearly one fifth of 329 patients with documented dementia continued to drive after the onset of dementia, and impaired driving ability was noted in two-thirds of these. Their families experienced great difficulty in persuading patients to stop driving, and had to invoke outside help in many cases. Neuropsychological tests did not help to identify those who drove badly while activity of daily living scores were related to driving ability. These findings suggest that many patients with dementia drive in an unsafe fashion after the onset of the illness. The present system of self-certification of health by the elderly for driver-licensing purposes needs to be reassessed. PMID- 1433060 TI - 'I thought it would go away': patient denial in breast cancer. AB - A significant proportion of patients with cancer present late to the doctor. The characteristics of these patients and the reasons behind their delaying behaviour is poorly understood. In this study a group of 30 women with breast cancer who delayed their presentation were compared with a randomly selected group with the same disease. The women who presented late did not appear to fit into any particular socio-demographic category, but examination of their histories revealed widespread denial of illness and a diversity of beliefs and behaviour. PMID- 1433059 TI - Laxative induced diarrhoea--a neglected diagnosis. AB - A laxative screening service was established and offered to gastroenterologists in hospitals covering the West and Central belt of Scotland. The prevalence of laxative induced diarrhoea was assessed in two populations and was found to be 4% in new patients presenting to a gastroenterology clinic with diarrhoea and 20% in patients already under investigation of chronic idiopathic diarrhoea. A high rate of missed diagnosis of laxative induced diarrhoea (71%) and a low request rate (eight per annum) confirm the low clinical awareness of this diagnosis. We found potential savings of 80% of the cost of investigations subsequently ordered which could have been avoided by performing laxative screens on all patients presenting with diarrhoea. The introduction of such a screening policy is recommended as a cost-effective measure. PMID- 1433061 TI - The Ring total knee replacement--a comparison of survivorship. AB - Long term results of joint replacement are frequently expressed as survivorship; it therefore becomes increasingly important to have the ability to make valid comparisons between survivorship tables in order to determine accurately the statistical significance of published differences. We present a statistical method for direct comparison of survivorship tables. We have applied this technique to evaluate the survivorship of the unconstrained, uncemented Ring total knee replacement first implanted in 1975 and compare this to contemporaneous constrained prostheses. There is a significant improvement in survival, which suggests a beneficial long-term effect on the bone/implant interface of this changing design concept. PMID- 1433062 TI - An audit of university education in trauma and orthopaedic surgery in Great Britain. AB - An audit of undergraduate trauma and orthopaedic surgery teaching was carried out in 24 of the 27 medical schools in Great Britain and major differences were found between the medical schools. The range of time spent in teaching trauma and orthopaedic surgery for undergraduates varied from 3 weeks to 12 weeks and in five out of 27 medical schools trauma and orthopaedic surgery tuition was split between various years of the clinical curriculum. In some schools there were 30 students on a firm and in others only one. The opportunity for undergraduates to give feedback to their teachers, the use of objective assessment at the end of such an appointment by the teachers, varied between medical schools. To avoid some of these very basic differences between our medical schools, the teaching of clinical subjects to undergraduates in medicine should be reviewed nationally and minimum standards set. PMID- 1433063 TI - Cigarette smoking and its relationship to inflammatory bowel disease: a review. PMID- 1433064 TI - The Biddenden Maids: a curious chapter in the history of conjoined twins. PMID- 1433065 TI - PET imaging and cognition in schizophrenia. PMID- 1433066 TI - Cerebral blood flow and mental processes in schizophrenia. AB - The patterns of cerebral blood flow associated with three syndromes of schizophrenic symptoms are compared with the loci of cerebral activation in normal subjects during the performance of mental processes implicated in the three syndromes. The psychomotor poverty syndrome, which has been shown to involve a diminished ability to generate words, is associated with decreased perfusion of the dorsolateral prefrontal cortex at a locus which is activated in normal subjects during the internal generation of words. The disorganization syndrome, which has been shown to involve impaired suppression of inappropriate responses (eg in the Stroop test), is associated with increased perfusion of the right anterior cingulate gyrus at a location activated in normal subjects performing the Stroop test. The reality distortion syndrome, which evidence suggests arises from disordered internal monitoring of activity, is associated with increased perfusion in the medial temporal lobe at a locus activated in normal subjects during the internal monitoring of eye movements. PMID- 1433067 TI - Abnormalities of cerebral structure in schizophrenia on magnetic resonance imaging: interpretation in relation to the neurodevelopmental hypothesis. AB - The nature of abnormalities of cerebral structure evident in schizophrenia on magnetic resonance imaging is considered in relation to the neurodevelopmental hypothesis of the disorder. While schizophrenic patients showed increased ventricular volume, the extent of increase with age was comparable with that evident in controls and was unrelated to duration of illness. Conversely, cortical atrophy was evident only in patients, and this increased markedly with age and duration of illness. Such findings could be suggestive of two distinct pathophysiological processes in schizophrenia, but a schema for their reconciliation with the neurodevelopmental hypothesis is elaborated. PMID- 1433068 TI - PET imaging in Alzheimer's disease. PMID- 1433069 TI - Squamous cell carcinoma complicating lichen planus of the lip. PMID- 1433070 TI - Squamous cell carcinoma arising in rhinophyma. PMID- 1433071 TI - A case of malignant epithelioid schwannoma arising on the face. PMID- 1433072 TI - Association of migrainous headaches with Gasserian ganglial ablation. PMID- 1433073 TI - Acquired immunodeficiency syndrome in the elderly: two case reports. PMID- 1433075 TI - Clinical trial results: whose responsibility? PMID- 1433074 TI - Monitoring of triplet pregnancy during labour. PMID- 1433076 TI - Asymptomatic hypothyroidism and hypercholesterolaemia. PMID- 1433077 TI - Successful treatment of neonatal purpura fulminans with epoprostenol. PMID- 1433078 TI - Career blight following operating theatre injuries. PMID- 1433079 TI - Surgical audit and mortality review. PMID- 1433081 TI - An alternative weekend on call. PMID- 1433080 TI - What's in a name? PMID- 1433082 TI - Mind your language. PMID- 1433083 TI - Vaginal fistulae. PMID- 1433084 TI - Vesico-vaginal and recto-vaginal fistulae. AB - A personal series of 716 patients with vesico-vaginal and/or recto-vaginal fistulae is presented. Five hundred and seventy-eight patients were managed in Africa, mainly at the Addis Ababa Fistula Hospital, while 138 were kindly referred to me from various parts of Britain. The main cause of such fistulae in the developing world is pressure necrosis from obstructed labour. In the developed world the aetiology is surgery, malignancy, radiotherapy or a combination of these. Other causes include neglected foreign bodies, coital injury and local treatment by an unqualified practitioner. A vesico-vaginal fistula alone was present in 78.8%, a recto-vaginal fistula alone in 4.3%, while 16.9% of patients had both a vesico-vaginal and a recto-vaginal fistula. Six hundred and six (84.6%) patients were cured at the first attempt at repair, 45 (6.3%) failed and 65 (9.1%) had stress incontinence. PMID- 1433085 TI - The spectrum of brittle diabetes. AB - A group of 42 severely brittle insulin dependent diabetic patients were studied, and compared with a similar number of 'stable' diabetic patients. Brittle diabetics were predominantly female (86% v 45%, P < 0.01), were of younger age (mean +/- SD 27.9 +/- 12.8 years v 40.1 +/- 13.6 years, P < 0.001), and of shorter duration of diabetes (13.7 +/- 9.4 years v 19.6 +/- 11.2 years, P < 0.01). Control as measured by glycosylated haemoglobin (HbA1) was poorer (13.7 +/ 3.1% v 10.1 +/- 1.5%, P < 0.001), and daily insulin dose higher (98 +/- 81 u v 47 +/- 14 u, P << 0.001). There was no difference in diabetic complication rates, but psychosocial disturbances (74% v 17%) and factitious instability (40% v 2%) were highly significantly more common amongst brittle patients. Examination of patterns of admission revealed most brittle diabetics to have hyperglycaemic problems (70%), mainly due to recurrent ketoacidosis (52%). Recurrent hypoglycaemia accounted for 12% of the group, and only 5/42 patients (12%) had mixed forms of instability. Brittle diabetes is thus characterized by young age and female sex, and usually manifests itself as recurrent ketoacidosis or other forms of hyperglycaemic instability. Psychosocial problems and factitious metabolic decompensation are common. PMID- 1433086 TI - Infective endocarditis in a district general hospital. AB - Thirty-three cases of infective endocarditis presenting during a 6.5 year period to a district general hospital were analysed retrospectively. The annual incidence was 22 cases per million population. Twenty-two cases had pre-existing cardiac disease, mainly valvular disease-usually rheumatic (nine cases) and prosthetic valves (10 cases). Recognizable precipitants such as recent surgery were uncommon. Two cases presented after deliberate drug overdose possibly due to depression exacerbated by systemic disease. Symptoms were usually non-specific. All but two cases had murmurs and most were pyrexial. Splinter haemorrhages and clubbing were seen in about 20% of cases. Viridans-type streptococci were the commonest infecting organisms (14 cases). Staphylococcal infection (six cases) was confined to intravenous drug abusers and patients with prosthetic valves. Five cases were culture negative. Cardiac failure was present in 13 cases at presentation and developed in seven others during treatment. Acute valve replacement was necessary in eight cases, and late replacement in three. Renal impairment (plasma urea > 8 mmol/l and/or plasma creatinine > 120 mumol/l) occurred in 19 cases during the course of their illness. Embolic phenomena occurred in 12 patients and mostly involved the central nervous system. In the 8 fatal cases, the cause of death was cardiac failure in six, cerebrovascular accident in one, and myocardial infarction in one. Four of the six patients who subsequently died of cardiac failure had been referred for surgery. Both those who were not referred had coexisting medical problems. Factors associated with increased mortality were age, male sex, cardiac failure (P < 0.01), renal impairment (P < 0.05), and embolic phenomena (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433087 TI - Long term use of transcutaneous electrical nerve stimulation at Newcastle Pain Relief Clinic. AB - This retrospective study of long-term use of transcutaneous electrical nerve stimulation (TENS) at Newcastle Pain Relief Clinic indicates that TENS has been a successful analgesic treatment for 58.6% of 1582 patients attending the clinic over a period of 10 years. A wide range of pain conditions were found to respond to TENS and many patients continued to use the treatment for several years. Most patients not responding to TENS (during a home trial) returned stimulators at the first follow-up appointment. Thus TENS should be considered as a simple, safe and reusable first line treatment for many pain conditions. PMID- 1433088 TI - Critical ischaemia of the upper limb. AB - Fifty-seven patients who presented to the Royal Surrey County Hospital, Guildford, with critical upper limb ischaemia between 1980 and 1989 were studied. Only 13 patients had emboli, while 23 presented with arteritis, seven involving large vessels and 16 with small vessel disease. Other causes included nine patients with trauma, six with atherosclerosis (of whom five were women), and four with vascular complications of thoracic outlet obstruction. Single examples of ischaemia due to radiation fibrosis and disseminated intravascular coagulation were also seen. Critical ischaemia of the upper limb remains an uncommon yet challenging problem. The review demonstrates that total limb arteriography should be performed in all patients, except the minority who present with direct arterial trauma or classical emboli. PMID- 1433089 TI - Renal conservation in the management of bilateral renal tumours. AB - We report five patients with bilateral tumours and review their management which include many of the therapeutic options that are available. PMID- 1433090 TI - Why 100 patients failed to keep an outpatient appointment-audit in a dermatology department. AB - Failure to keep outpatient appointments is common at all clinics and various explanations may be offered. One hundred attending patients who had failed to keep their previous dermatology clinic appointment were asked the reason for their non-attendance. Many and varied reasons were given but illness (28%), and problems related to appointments (33%) were prominent. They were also asked how they had obtained a further appointment. Stricter follow-up of non-attenders by the hospital including informing the GP, and subsequent GP action if necessary, may improve attendance figures. PMID- 1433091 TI - Bringing about change: the introduction of secure units. AB - The introduction of regional secure units into the NHS was studied as one example of the diffusion of patient care innovations. As well as the general history of secure units events in four Regions were studied in detail for the period from 1974 up to mid-1983. It is concluded that secure units became gradually more acceptable over time as (i) the need for such units was recognized, (ii) the climate of opinion changed in psychiatric hospitals from seeing secure units as a retrograde step, following the acceptance of more open door policies, to seeing secure units as a prestige development which might safeguard the future of a particular hospital, (iii) government loosened the definitions of what secure units should be and how they should operate so that there was more room for different regions to assess their own needs. Regions which were able to move relatively fast on secure unit development were those where there was already a 'product champion' present to promote the ideas, usually a forensic psychiatrist, and where there was also managerial support and designated responsibility for secure unit development at local and regional level. It is concluded that while public reaction was a hindrance it did not slow down secure unit development as much as might have been expected. PMID- 1433092 TI - Annie--a management and resource problem: discussion paper. PMID- 1433093 TI - Progress with a recombinant whooping cough vaccine: a review. PMID- 1433095 TI - Premier Chirurgien du Roi: the life of Ambroise Pare (1510-1590) PMID- 1433096 TI - Pancreatic pseudocyst due to fractured pancreas. PMID- 1433094 TI - Excitatory events associated with propofol anaesthesia: a review. PMID- 1433097 TI - Budd-Chiari syndrome in association with polycystic disease of the liver and kidneys. PMID- 1433098 TI - Choledochal cyst in adulthood. PMID- 1433100 TI - Peerless haemangiomata. PMID- 1433099 TI - Brave biopsy. PMID- 1433101 TI - Bone marrow necrosis and disseminated intravascular coagulation in disseminated carcinoma. PMID- 1433102 TI - Pituitary surgery and inappropriate antidiuretic hormone secretion. PMID- 1433103 TI - Treatment of tumour-induced hypoglycaemia with human growth hormone. PMID- 1433104 TI - Polarization of art and science. PMID- 1433105 TI - Subtotal colectomy following marathon running in a female patient. PMID- 1433106 TI - Crohn's disease of the vulva. PMID- 1433107 TI - Gut fermentation. PMID- 1433108 TI - What is the best dosage schedule for patients? PMID- 1433109 TI - Sarcoidosis and acute leukaemia. PMID- 1433111 TI - Another look at holistic medicine. PMID- 1433110 TI - Use of emergency ambulance service. PMID- 1433112 TI - Reactions to food additives. PMID- 1433113 TI - Diet and coronary heart disease: why blame fat? PMID- 1433114 TI - Spasmodic torticollis. PMID- 1433115 TI - Antineutrophil cytoplasmic antibody and the gastroenterologist. PMID- 1433116 TI - The portrayal of the physician in non-medical literature-resentment, confrontation, litigation. PMID- 1433117 TI - Botulinum toxin treatment of spasmodic torticollis. AB - We reviewed the efficacy and adverse effects of repeated botulinum toxin injections into hyperactive neck muscles of 107 successive patients with spasmodic torticollis. They received 510 injection treatments over a median period of 15 months (range 3-42 months). One patient failed to benefit at all, but 101 (95%) patients reported considerable (moderate or excellent) benefit from at least one treatment. On a global subjective response rating, 93% of 429 treatments resulted in some improvement and 76% in moderate or excellent improvement. Pain reduction followed 89% of 190 treatments with moderate or excellent reduction after 66%. Median duration of benefit was 9 weeks. All torticollis types responded equally well and injections into two (or more) involved neck muscles were more effective than injection into a single muscle. The most frequent adverse effect was dysphagia, occurring after 44% of all treatments, but this was severe after only 2%. Antibodies to botulinum toxin were detected in the serum of three out of the five patients in whom loss of treatment efficacy occurred. We conclude that botulinum toxin treatment is the most effective available therapy for spasmodic torticollis and practical advice is provided for anyone wishing to set up the technique. PMID- 1433118 TI - Ceftazidime versus aminoglycoside and (ureido)penicillin combination in the empirical treatment of serious infection. AB - Urgent treatment of serious infections with broad spectrum antibiotics usually starts before bacteriological evidence of the infective organism(s) becomes available. In this study 471 patients with a clinical diagnosis of sepsis were treated empirically with ceftazidime (CAZ) monotherapy (249 patients), or with an aminoglycoside+(ureido)penicillin combination (AG+PEN) (222 patients) to establish clinical outcome and bacteriological response. Up to 72 h post treatment 94.5% of patients in the CAZ group and 93.8% in the AG+PEN group were treated successfully (treatment difference 0.7%, P < 0.01, 95% confidence interval -3.8%, 5.2%); 2-4 weeks after treatment neither regimen proved clinically superior. The differences in bacteriological response up to 72 h, and at 2-4 weeks after treatment, were 5.6% and 12.4% in favour of CAZ, however, these were not statistically significant. Overall, 56 patients reported 72 adverse events in the CAZ group, compared with 33 patients reporting 41 adverse events in the AG+PEN group. Deaths, 40 on CAZ and 21 on AG+PEN, were mainly related to their underlying condition. The two regimens were shown to be clinically equivalent in seriously ill patients treated empirically. PMID- 1433119 TI - Nitrous oxide-oxygen analgesia: the performance of the MC mask delivery system. AB - Nitrous oxide administration via an oxygen facemask such as the Mary Catterall (MC) is an accepted technique for supplementing regional anaesthesia. This study assessed the range of nitrous oxide and oxygen concentrations delivered to the trachea using a mechanical lung model. The inspired concentrations of these two gases were determined by the total fresh gas inflow rates, their concentrations in the fresh gas mixture and the peak inspiratory flow rate of the analogue lung. A 1:1 nitrous oxide-oxygen mixture in the fresh gas with an inflow rate of 4-6 l/min is recommended to ensure adequate oxygen delivery into the trachea as well as achieving the therapeutic concentrations of nitrous oxide (20-30%). PMID- 1433120 TI - Monospot and VP1 tests in chronic fatigue syndrome and major depression. AB - Thirty-four patients with chronic fatigue syndrome (CFS) were compared with controls with DSM-III-R major depression on the Monospot and VP1 antigen tests. There was no significant difference in the numbers initially VP1 positive in the groups (11/34 and 7/34 positive in the chronic fatigue and major depression group respectively). Four CFS but no depressed patients were Monospot positive initially. No patient was both Monospot and VP1 positive. Patients positive on the tests were offered a repeat 6 months later. Eight of the 11 VP1 positive patients in the CFS group were retested and four remained positive, but none of the four depressed patients retested remained positive. No patient retested remained Monospot positive. The Monospot and VP1 tests appear to have little discriminating ability between these groups as screening tests and their predictive validity is unclear. PMID- 1433121 TI - Aerobic exercise in the adjunctive treatment of depression: a randomized controlled trial. AB - Two clinical trials have been conducted in a sample of depressed patients to determine whether the addition of an aerobic exercise programme to their usual treatment improved outcome after 12 weeks. In the first trial, an aerobic exercise group had a superior outcome compared with a control group in terms of trait anxiety and a standard psychiatric interview. A second trial was then conducted to compare an aerobic exercise programme with low intensity exercise. Both groups showed improvement but there were no significant differences between the groups. In neither trial was there any correlation between the extent of change in the subjects' physical fitness due to aerobic exercise and the extent of the improvement of psychiatric scores. PMID- 1433122 TI - Management of hypopharyngeal carcinoma: a 6-year review. AB - A retrospective review of 16 consecutive cases of squamous carcinoma of the hypopharynx treated by pharyngo-laryngo-oesophagectomy (PLO) and gastric transposition with a thoracotomy as part of the surgical technique is presented. An operative mortality of 6% and a hospital mortality of 12% occurred. Other complications are discussed. No significant morbidity or mortality occurred as a result of the thoracotomy. A comparison is made with the extra-thoracic technique of gastric transposition. PMID- 1433124 TI - The unfolded shape of the brain. PMID- 1433123 TI - Acrokeratosis paraneoplastica of Bazex. AB - Bazex disease is one of the rarer cutaneous paraneoplastic syndromes. It is characterized by psoriasiform changes on the digits, and in some patients spread to the ears, nose and in later stages to the limbs and trunk. The associated malignancy is typically a squamous cell carcinoma of the upper aerodigestive tract. We review the literature regarding acrokeratosis paraneoplastica of Bazex and report three cases which illustrate both the typical and some of the less common changes that are seen in the condition. PMID- 1433125 TI - Should we ban the mercury thermometer? Discussion paper. PMID- 1433126 TI - Empirical use of exclusion diets in chronic disorders: discussion paper. PMID- 1433127 TI - Food allergy--fact or fiction: a review. AB - Food sensitivity is a common condition presenting with various clinical syndromes including migraine, urticaria, gluten enteropathy, Crohn's disease and irritable bowel syndrome. It is a heterogeneous condition affecting different organ systems and is also aetiologically diverse with subgroups due to allergy, pharmacological reactions, enzyme deficiencies and psychological causes. Clinical acceptance of food sensitivity has been delayed by the use of dubious diagnostic techniques by a minority of practitioners and the lack of laboratory diagnostic tests, but several double blind studies have now fully validated the existence of food sensitivity syndromes. More widespread recognition of food sensitivity would be cost effective for the National Health Service. PMID- 1433128 TI - Sir Frederick Treves: surgeon, author and medical historian. PMID- 1433129 TI - Brodie's tracheostomy. PMID- 1433130 TI - Ureteric and duodenal obstruction due to inflammatory abdominal aortic aneurysms. PMID- 1433131 TI - Extensive and unusual Mongolian blue spots in a child with GM1 gangliosidosis type one. PMID- 1433132 TI - Association between pyoderma gangrenosum and ulcerative colitis. PMID- 1433133 TI - Tracheal compression by a cervico-mediastinal haematoma. PMID- 1433135 TI - Granular cell tumour: an underdiagnosed cause of multifocal subcutaneous swellings. PMID- 1433134 TI - Adrenal apoplexy after coronary artery bypass surgery leading to Addisonian crisis. PMID- 1433136 TI - Persistent diplopia following streptococcus suis type 2 meningitis. PMID- 1433137 TI - Premier Chirugien du Roi: the life of Ambroise Pare. PMID- 1433138 TI - Ultrasound and the Alvarado score. PMID- 1433139 TI - Folklore of warts. PMID- 1433140 TI - Transcultural medical encounters. PMID- 1433141 TI - Does atmospheric nitrous oxide (N2O) affect the perception of energy and mood? PMID- 1433142 TI - Healthcare workers and hepatitis B. PMID- 1433143 TI - Chronic fatigue syndrome and heterogeneity. PMID- 1433144 TI - Fluctuations in perceived energy and mood among patients with chronic fatigue syndrome. PMID- 1433145 TI - Dietary habits of school-children in Bahrain. AB - A multistage stratified sampling procedure was used to select 1673 Bahraini school children (871 boys and 802 girls) to study their food habits. The results revealed that breakfast was more often skipped than lunch and supper by both sexes. Significant differences in the food consumption between boys and girls were noticed at morning snack; beef burgers, liver and egg sandwiches were more consumed by boys, while girls preferred carbonated beverages, cheese, uncarbonated canned drinks and broad beans. The foods consumed at lunch were very similar to those of the adult population in Bahrain. However, the percentage of fresh fruits consumed at lunch was almost double by girls (31.9%) than boys (17.1%). Corn-puffs, carbonated beverages, chocolates, uncarbonated canned drinks and fruits were the main foods consumed at afternoon snack. Boys were more likely to consume tea, meat, eggs, cheese and rice at supper, while girls preferred cheese, corn-puffs and carbonated beverages. Age has also a significant influence on dietary habits. The consumption of bread at breakfast decreased with age while the consumption of carbonated beverages at morning snack increased remarkably with age. In general the meal and snack patterns of school children vary considerably with age and sex. PMID- 1433146 TI - Fish mongers and public awareness on fish-food hygiene in Nigeria. AB - Sale of fish is a thriving business in Nigeria because of the high demand for fish. However, there is lack of public awareness on the need for fish hygiene by fish mongers and consumers. This paper discusses the issue of hygiene as it affects a fish shop environment, insects and pests of fish, preservation, handling, transportation, packaging, fish marketing and distribution. Suggestions on improving fish food hygiene and strategies for establishing fish guidelines and inspections are highlighted. PMID- 1433147 TI - Suspected synergism between consanguinity and familial aggregation in type 2 diabetes mellitus in Saudi Arabia. AB - A retrospective study of 210 cases of diabetes was carried out at King Khalid University Hospital diabetes clinic to delineate etiologic factors in non-insulin dependent diabetes mellitus (NIDDM). Standardised detailed questionnaires were administered to both cases and controls and the information sought included general demographics, dietary patterns, anthropometric values, family history, consanguinity and familial aggregation of Diabetes Mellitus (DM). Familial aggregation yielded an odds ratio of 6:2 which suggests a causal association with DM. A synergistic effect of familial aggregation was observed which needs to be further explored in future studies. PMID- 1433148 TI - Cerebral neurocysticercosis--case report and review. PMID- 1433149 TI - Sampling in epidemiological research: a case study of the prevalence of brucellosis in Saudi Arabia. AB - The superficial description in biomedical journals of sampling methods used in epidemiological studies of the prevalence of some diseases can be attributed to shallow knowledge of basic sampling techniques. The population of interest in most community surveys is usually very large and resources and time available limited, so that researchers have little or no choice but to study a sample of the population. One of the basic principles of sampling is the avoidance of bias, guaranteed by taking a random sample. But the term 'random sample' has often been misinterpreted as synonymous with 'haphazard sample', taking a sample without a definite pattern. It is re-emphasised that a random sample is a probability sample that gives every unit in the population a known probability of being selected in the sample. The procedures for taking a random sample for a nationwide study in the Kingdom of Saudi Arabia are not easy because of the structure of the population, and therefore require more complex sampling methods like the stratified cluster sampling. It is also necessary in a stratified sample to calculate estimated persons affected by a condition for each selected subgroup of the population before obtaining the overall prevalence rate. A proper understanding and use of appropriate sampling techniques is most likely to result in the most desired representative sample, and guarantees that some underlying assumptions for inferential statistics will be satisfied. PMID- 1433150 TI - Children and the citizens charter. PMID- 1433151 TI - The challenge of menopause education in isolation. PMID- 1433152 TI - Assessment and evaluation of the International Water Decade. AB - The International Drinking Water Supply and Sanitation Decade (1981-90) has ended without reaching its declared goal of providing all people with safe drinking water and proper sanitation. The effect of drinking water and sanitation on health has been established, and the 2 components have been included in the World Health Organization (WHO) global campaign for Health For All by the year 2000, and in the global Primary Health Care programme. The assessment of the achievements has been based on coverage rates expressed in percentage. The findings were computerised. High population growth rates in the developing countries hampered and reduced the coverage. Other hindering factors included the lack of appropriate technology, the preference of the small privileged urban areas over the vast rural areas, the lack of the simultaneous approach in the development of water and sanitation and poor involvement of health education in the activities of the Water Decade. The water and sanitation development activities of the last decade have to be carried forward and continued during the present decade, in a different approach and alternative methods. PMID- 1433153 TI - Food hygiene and the caterer (conference July 1991): training staff in food hygiene. PMID- 1433154 TI - Dignity, risks and responsibility in residential homes for elderly people. PMID- 1433155 TI - Risks, dignity & responsibility in residential homes for the elderly: privacy and protection--are they in conflict? PMID- 1433156 TI - Risks, dignity & responsibility in residential homes for the elderly: the legal framework. PMID- 1433158 TI - Public health in the United States. PMID- 1433157 TI - Risks, dignity & responsibility in residential homes for the elderly: freedom or restraint. PMID- 1433159 TI - Equal blood pressure levels carry different risks in different risk factor combinations. AB - It is well known that combinations of risk factors result in higher risk than their mere sum. The present paper describes, in quantitative terms, the differences between risks pertaining to equal blood pressure elevations at different constellations with other risk factors (smoking and hypercholesterolaemia). From the practical point of view, this concept of 'constellation risk' convincingly underscores the need for controlling, in hypertensive patients, coexisting hypercholesterolaemia and smoking. Also, at equal blood pressure elevations, smoking and hypercholesterolaemic patients are in greater need of antihypertensive medication. This applies in particular to the range of mild hypertension, where individual decisions have to be taken whether to initiate drug treatment. PMID- 1433161 TI - Reproducibility of measurements of blood pressure in a tropical environment. AB - The reproducibility of measurements of the blood pressure of 65 adult male Gambians was investigated to assess the role that replication of measurements may have in epidemiological studies in a tropical environment. Observations were made at approximately seven week intervals over a period of 15 months and measurements were repeated three times on each occasion a subject was seen. The magnitude of the variation of an individual subject's BP between occasions, and between readings on the same occasion, was comparable with those which have been observed in studies in developed countries in temperate climates. The variation between occasions was greater than that between readings on the same occasion. There was a significant fall in systolic pressure between the first and third occasions, and a more gradual fall in diastolic pressure. The observations suggest that an individual subject's BP level would be better characterized by making a second reading on another occasion than by making three or more readings on the same occasion. These results have implications for the design of epidemiological studies and for the diagnosis of hypertension in the tropics. PMID- 1433160 TI - Haemodynamic contributions to post-exercise hypotension in young adults with hypertension and rapid resting heart rates. AB - The haemodynamic effects of 45 min of treadmill exercise (at 70% of resting heart rate reserve) were determined in 5 young adults with hypertension and rapid resting heart rates (greater than 90 beats/min in clinic) and were compared with those of 5 age-matched normotensive subjects. Blood pressure was lower after exercise in the hypertensive, but not the normotensive subjects. Mean cardiac output before exercise was similar in the two groups, and fell from 6.8 +/- 0.6 before to 5.4 +/- 0.6 l/min 60 min after exercise in the hypertensive group (P less than 0.01). Total peripheral resistance tended to be higher at this time. Neither variable was affected by prior exercise in the normotensive group. The depressor effects of prior exercise on mean arterial pressure (-8.6 +/- 1.0 vs. 1.4 +/- 2.5 mmHg; P less than 0.04) and cardiac output (-1.4 +/- 0.3 vs. -0.1 +/- 0.1 l/min; P less than 0.005) and the increase in total peripheral resistance (+3.0 +/- 1.2 vs. 0.0 +/- 1.0 Units; P less than 0.05) were greater in the hypertensive group. Thus, the post-exercise hypotension in this selected group of young hypertensive subjects with rapid resting heart rates was mediated by a decrease in cardiac output and stroke volume disproportionate to the fall in blood pressure, suggesting sustained compromise of their cardiac performance after acute exercise. PMID- 1433162 TI - Demographic, life style and anthropometric correlates of blood pressure of Nigerian urban civil servants, factory and plantation workers. AB - Demographic, life style and anthropometric correlates of blood pressure were analysed in 5,200 civil servants, factory and plantation workers living in an urban setting in the South Eastern part of Nigeria. The subjects were 4,382 men (84.2%) and 818 (15.8%) women. The prevalence of hypertension, using the WHO criteria among the workers was 8.1%, and was lower in women than men, 3.5% and 8.9% respectively. Only 19.6% of the hypertensive population knew that they had hypertension, whilst 29.4% of the total population under study gave a positive family history of hypertension. The blood pressure and the prevalence of hypertension rose with age, number of children in the family, salary scale and with the number of cigarettes smoked per day. The prevalence of hypertension was higher in medium and heavy drinkers than the non-drinkers and light drinkers. The prevalence was also higher in medium and heavy smokers. Multiple regression analysis showed a significant positive relation between the systolic blood pressure and sex, age, marital status, number of children in the family, salary scale, tobacco consumption and weight (P less than 001). On the other hand, occupation (P less than 01) educational qualification (P less than 001), support system (P less than 03) and height (P less than 001) had significant negative relationships with systolic blood pressure. There was also a significant positive relation between the diastolic blood pressure and number of children in the family (P less than 002) and salary scale (P less than 001). It is suggested that hypertension screening and treatment should be incorporated in the primary health care programmes of African communities. PMID- 1433163 TI - Feasibility of a long-term low-sodium diet in mild hypertension. AB - The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice. After screening and a run-in phase of 6-8 weeks, a total of 77 previously undiagnosed mildly hypertensive patients were identified. Half of them were randomized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage; the others were randomized to receive no advice. The patients were followed up for 12 months with quarterly visits. A total of 56 patients (72.7%) completed the study, 26 on a low-sodium diet (LD) and 30 on their usual diet (UD). At each visit in the diet phase, patients provided 24h urine, which was analysed for volume and sodium concentration in order to assess their sodium intake. Blood pressure, heart the rate and body weight were recorded. The mean urinary sodium excretion for all diet phase visits overlapped in the two groups (177.0 +/- 32.9 vs. 169.3 +/- 49.4 mEq/24h respectively in the LD and UD groups). Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group (144.2 +/- 11.1/91.6 +/- 6.4 and 148.0 +/- 13.7/95.6 +/- 4.7 mmHg respectively, P less than 0.01). Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions, the only ones suitable for widespread application in general practice. PMID- 1433164 TI - Urinary salt titrator stick: a useful and quick estimate of dietary sodium intake? AB - Repeated measures of urinary salt excretion are the best compromise between reliability and convenience for estimating dietary salt intake. In order to assess the accuracy of the Uropaper urinary salt titrator stick (giving discrete readings of 4, 6, 8, 10, 12 or 14 g/l of NaCl), 312 urine samples were analysed both with the stick and with an ion-selective electrode. There was a good stick electrode correlation in all the 312 samples (r = 0.84). With a tolerance of +/- 1 g/l, the percentages of correct estimations dropped from 82% to 33% with increasing concentrations of NaCl in the urinary sample. For NaCl concentrations greater than 8 g/l (137 mmol/l) the error in the stick measurement consisted almost exclusively of overestimation of the electrode readings. These results were unaffected by the concentration of urinary potassium. No discrepancies were found among three different readers. This stick is easy to use and measures, with reasonable accuracy, low urinary NaCl concentrations. It could be useful for self monitoring during low NaCl diets. PMID- 1433165 TI - Blood pressure and urinary cations in a Chinese population. AB - The prevalence of hypertension and the relationship between blood pressure, age, body mass index (BMI) and urinary cations from casual urine specimens were examined in 1,513 Chinese employees of a public utility company and non-medical personnel of a district hospital. The prevalence of hypertension, defined as systolic blood pressure greater than or equal to 140 or a diastolic blood pressure greater than or equal to 90 mmHg, or a past history of hypertension, was 17% in men and 5% in women. After excluding subjects who were on antihypertensive medication, age, body mass index, and urinary sodium/potassium ratio were independently and positively associated with blood pressure, while urinary potassium/creatinine ratio was inversely related to blood pressure. No association with urinary sodium or sodium/creatinine ratio was found. Higher mean blood pressure in men was accompanied by lower urinary potassium/creatinine and potassium concentration and higher sodium/potassium ratio, even though men had the same mean BMI when compared with women. A difference in potassium intake between the sexes may partly account for this finding. We conclude that in this Chinese population, whose dietary intake is more influenced by the West compared with Chinese in the Peoples' Republic of China, age and BMI are important determinants of blood pressure, together with potassium intake as reflected by urinary potassium excretion. No association of blood pressure with sodium excretion was demonstrated. PMID- 1433166 TI - Blood pressure and 40 month mortality in elderly Chinese subjects aged 70 years and over. AB - The association between blood pressure and 4 year mortality was examined in a cohort of 970 Chinese subjects aged 70 years and above. After adjusting for age, sex, body mass index, smoking habit, place of residence, and the presence of heart or chronic lung diseases, a U-shaped association between blood pressure and mortality was observed, the risks of mortality among subjects in the extreme quartiles being twice as high as those in the middle quartiles. Subjects with the lowest systolic blood pressure quartile also had a higher risk of developing functional limitations. PMID- 1433168 TI - Complete spontaneous remission of cough induced by ACE inhibitors during chronic therapy in hypertensive patients. AB - The files of 172 consecutive hypertensive patients who received captopril or enalapril have been reviewed and the patients questioned on the development of chronic dry cough, persisting for at least two months. Forty patients had cough that was attributed to the drugs. Thirteen of them discontinued the drugs because of this adverse effect. In 15 of the 27 patients (55%) who continued receiving ACE inhibitors (7 males, 8 females, aged 65.4 +/- 9.9 years) the cough had spontaneously disappeared after 3.9 +/- 1.9 months of continued unaltered administration of these drugs and without any treatment aimed against this symptom. All patients were followed for at least four months after disappearance of cough, without recurrences. This finding may discourage withdrawal of ACE inhibitors from many patients who develop cough. Continuation of ACE inhibitors for at least several months, despite cough, (if the cough is not too severe) is probably justifiable. PMID- 1433167 TI - ACE inhibition in diabetic patients: effect on pressor responsiveness to noradrenaline. AB - The pressor responsiveness to noradrenaline was assessed before and after four weeks of treatment with enalapril (20 mg/day) in eight mild-to-moderate essential hypertensives, in eight normotensive type II diabetics and in eight mild-to moderate hypertensive type II diabetic patients. The ACE inhibitor interfered to the same extent with the renin-angiotensin system and did not alter noradrenaline kinetics in the three groups of patients, but significantly reduced the arterial responsiveness only in non-diabetic subjects. It is suggested that factors, such as an exaggerated sodium retention, might determine the lack of effect of enalapril in diabetic patients. PMID- 1433169 TI - Alfred Burger Award address. A half century in medicinal chemistry with major emphasis on pain-relieving drugs and their antagonists. PMID- 1433170 TI - Hypocholesterolemic activity of synthetic and natural tocotrienols. AB - Tocotrienols are farnesylated benzopyran natural products that exhibit hypocholesterolemic activity in vitro and in vivo. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase by a process distinct from other known inhibitors of cholesterol biosynthesis. An efficient synthetic route to tocotrienols and their isolation from palm oil distillate using an improved procedure is presented. gamma Tocotrienol exhibits a 30-fold greater activity toward cholesterol biosynthesis inhibition compared to alpha-tocotrienol in HepG2 cells in vitro. The synthetic (racemic) and natural (chiral) tocotrienols exhibit nearly identical cholesterol biosynthesis inhibition and HMG-CoA reductase suppression properties as demonstrated in vitro and in vivo. PMID- 1433171 TI - Synthesis and biological activity of trans(+-)-N-methyl-2-(3-pyridyl)-2 tetrahydrothiopyrancarbothioamide 1-oxide (RP 49356) and analogues: a new class of potassium channel opener. AB - The synthesis and biological activity of trans-(+-)-N-methyl-2-(3-pyridyl)-2 tetrahydrothiopyrancarbothioamid+ ++ e 1-oxide (8a, RP 49356) and analogues is reported. These compounds constitute a new structural class of K(+)-channel opener. The effects of changes in pyridyl group, thioamide, and thiane ring on in vitro K(+)-channel opening reactivity are discussed. A 3-pyridyl or 3-quinolyl group, a small N-alkyl thioamide function, and a thiane oxide ring, in which the sulfoxide is in a trans relationship to the thioamide, are preferred for activity. Selected compounds were tested intravenously in the normotensive anaesthetized rat for hypotensive effects, and the activities reflect their in vitro K(+)-channel opening activity. This led to further evaluation of compound 8a and the selection of the (-)-enantiomer 8b (RP 52891) for development as an antihypertensive and antianginal agent. PMID- 1433172 TI - 1-(2-Aminoethyl)-3-methyl-8,9-dihydropyrano[3,2-e]indole: a rotationally restricted phenolic analog of the neurotransmitter serotonin and agonist selective for serotonin (5-HT2-type) receptors. AB - A series of rotationally restricted phenolic analogs of the neurotransmitter serotonin has been synthesized with the 5-hydroxyindole portion of serotonin replaced by a dihydropyrano[3,2-e]-indole (1, 3, 4, and 5) and a dihydropyrano[2,3-f]indole (2). The receptor binding profile of these compounds has been studied and compared to the natural substrate serotonin. The dihydropyrano[3,2-e]indole derivatives (1, 3, 4, and 5) possess lower affinity for 5-HT1 receptors but equal or greater affinity for 5-HT2 receptors. Like serotonin, these compounds dose-dependently stimulated phosphatidylinositol turnover in rat brain slices. Moreover, the response to 1-(2-aminoethyl)-3-methyl 8,9-dihydropyrano[3,2-]indole (5, CP-132,484) and 1-(2-aminoethyl)-8,9 dihydropyrano[3,2-e]indole (4) is selectively antagonized by 5-HT2 receptor antagonists establishing these tryptamines as selective 5-HT2 receptor agonists. The high affinity and potency of 5 for 5-HT2 receptors suggests that the C5 hydroxy group in serotonin can function as a hydrogen bond acceptor in a 5-HT2 receptor with a directionality of interaction which is down and away from C6 in serotonin (Figure 5). Furthermore, the potent affinity of these compounds for 5 HT2 receptors coupled with their poor affinity for 5-HT1 receptors indicates that the aminoethyl side chain of serotonin adopts significantly different conformations in 5-HT1 versus 5-HT2 receptors. PMID- 1433173 TI - Antiallergic and cytoprotective activity of new N-phenylbenzamido acid derivatives. AB - A series of new N-phenylbenzamido acid derivatives was synthesized and evaluated for their ability to inhibit the IgE-mediated passive cutaneous anaphylaxis in the rat (PCA), as well as for their capacity to inhibit gastric mucosal damage induced by the oral administration of absolute alcohol in the rat. Some of these new derivatives exhibit potent antiallergic and cytoprotective activity, 20-80 times higher than that of the reference, disodium cromoglycate (DSCG). Structure activity relationships are discussed. The antiallergic activity of one of the more potent compounds of this series, i.e. 4-(1H-tetrazol-5-yl)-N-[4-(1H-tetrazol 5-yl)phenyl]benzamide (compound 44, CR 2039) was further evaluated in vivo. This compound antagonizes the bronchoconstriction induced by aerosolized ovalbumin in both anesthetized and conscious IgE sensitized guinea pigs with ID50 of 3.7 mg/animal (tracheal insufflation) and 20 mg/kg (im). Further cytoprotective effects were evaluated in gastric ulcer models induced by the acute oral administration of hypertonic sodium chloride solution or by acetic acid and by the subchronic administration of glucose in fasted animals. In the models used experimentally CR 2039 is effective, whereas DSCG seems to be devoid of any protective activity. Such a potent antiallergic and mucosal protectant could provide a new potential agent in the therapy of atopic allergic diseases. PMID- 1433174 TI - N1-hydroxylated derivatives of chlorpropamide and its analogs as inhibitors of aldehyde dehydrogenase in vivo. AB - Certain (arylsulfonyl)urea hypoglycemic drugs exemplified by chlorpropamide (CP) are known to interact pharmacologically with alcohol (ethanol) to elicit a chlorpropamide-alcohol flushing (CPAF) reaction that is reminiscent of the disulfiram-ethanol reaction (DER). In the present structure-activity study, designed to elucidate the mechanism of inhibition of aldehyde dehydrogenase (AlDH) by CP, we discovered that the N1-methoxy derivative of CP 2a was a potent inhibitor of AlDH in vivo similar in activity to that of the N1-ethyl derivative 2b. Both 2a and 2b can release n-propyl isocyanate, a known inhibitor of AlDH, nonenzymatically. However, (arylsulfonyl)carbamates that are structurally analogous to 2a were also active inhibitors of AlDH, whereas the corresponding (arylsulfonyl)carbamate analogs of 2b were uniformly without activity. We propose a mechanism of bioactivation of 2a and its analogs that involves initial O demethylation followed by disproportionation and solvolysis of the intermediate formed to release nitroxyl, the putative inhibitor of AlDH. PMID- 1433175 TI - Prodrugs of nitroxyl as inhibitors of aldehyde dehydrogenase. AB - In the preceding paper, analogs of chlorpropamide with an OMe substituent on the sulfonamide nitrogen were shown to inhibit aldehyde dehydrogenase (AlDH), and it was postulated that these compounds were bioactivated by O-demethylation to release nitroxyl (HN = O, nitrosyl hydride), which is an inhibitor of AlDH. Further evidence for the production of nitroxyl from compounds with O-acyl instead of OMe on the sulfonamide nitrogen is now presented. Thus, nitrous oxide (N2O), the end product of nitroxyl dimerization and disproportionation, was found to be generated on alkaline or enzymatic hydrolysis of N,O-diacylated N hydroxyarylsulfonamides. Since the latter compounds strongly inhibit yeast AlDH in vitro after bioactivation by an esterase intrinsic to this enzyme, nitroxyl generated from these compounds must be the common intermediate that inhibits AlDH. PMID- 1433176 TI - Truncated, branched, and/or cyclic analogues of neuropeptide Y: importance of the pancreatic peptide fold in the design of specific Y2 receptor ligands. AB - Truncated, branched, and/or cyclic neuropeptide Y (NPY) analogues were tested for their ability to bind to the neuroblastoma cells, SK-N-MC (Y1 receptor) and SK-N BE(2) (Y2 receptor). The design of such analogues was inspired by models of NPY based on the crystal structure of avian pancreatic polypeptide. The minimum length of the backbone was investigated using the following truncated analogues [binding affinity (nM) for Y1 and Y2 receptor subtypes respectively are given in parentheses]: des-AA10-17[D-Ala9]NPY (100, 0.9), des-AA7-23[D-Ala6]NPY (> 1000, 1.2), des-AA4-26[D-Ala3]NPY (> 1000, 120), cyclo(7,20)-des-AA10-17[Glu7,D- Ala9,D Dpr20]NPY (100, nd), cyclo(2,27)-des-AA7-23[Glu2,D-Ala6,D-Dpr27]NPY (> 1000, 3.6), cyclo(2,30)- des-AA7-23[Glu2,D-Ala6,-D-Dpr30]NPY (> 1000, nd), cyclo(1,30) des-AA4-26[Glu1,D-Ala3,D-Dpr30]NPY (> 1000, > 1000). A new family of branched NPY analogues corresponding to the partial deletion of the polyproline helix with conservation of the N-terminus was also examined: des-AA7-23[(Ac-NPY14-22) epsilon-D-Lys6]NPY (> 1000, 2.1), des-AA7-23[(Ac-NPY7-22)-epsilon-D-Lys6]NPY (> 1000, 5.1), des-AA7-23-[(Ac-LEALEG-NPY14-22)-epsilon-D-Lys6]NPY (> 1000, 4.8). Finally, the role played by the flexible tail (residues 32-36) was studied with the following cyclic analogues: cyclo(30,34)-[Lys30,Glu34]NPY18-36 (> 1000, 360), cyclo(30,34)-[Orn30,Gly34]NPY18-36 (> 1000, 950), cyclo(30,34)-[Dpr30,Glu34]NPY18 36 (> 1000, 590), cyclo(33,36)-[Lys33,Glu36]NPY (> 1000, > 1000), cyclo(33,36) [Lys33,Glu36]NPY18-36 (> 1000, > 1000). These results suggest that the Y1 receptor is highly discriminatory since deletion of residues 10-17, shown to have little effect on Y2 binding affinity, reduces Y1 affinity 50-fold. Bridging sites and constructs have been identified that may serve as useful leads in the design of more potent and selective analogues. We have identified two positions (9 and 6) where the introduction of a D amino acid is not detrimental to binding affinity. Whether this modification leads to the stabilization of a yet unidentified turn compatible with high Y2 receptor affinity will have to be determined by spectroscopic methods. Finally, stabilizing a putative alpha helical conformation of the C-terminal heptapeptide of NPY18-36 has a deleterious effect on the Y1 and Y2 receptors. PMID- 1433177 TI - Synthesis and antitumor activity of 3- and 5-hydroxy-4-methylpyridine-2 carboxaldehyde thiosemicarbazones. AB - To develop an alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone with clinical utility as an anticancer agent, two analogues, 3-hydroxy-4 methylpyridine-2-carboxaldehyde thiosemicarbazone (3-HMP) and 5-hydroxy-4 methylpyridine-2-carboxaldehyde thiosemicarbazone (5-HMP), of 5-hydroxypyridine-2 carboxaldehyde thiosemicarbazone (5-HP) have been designed and synthesized by two different methods. 3-HMP and 5-HMP both showed better antitumor activity than their respective parent compounds, 3-hydroxypyridine-2-carboxaldehyde thiosemicarbazone and 5-HP, in mice bearing the L1210 leukemia. PMID- 1433178 TI - Synthesis and antitumor activity of amino derivatives of pyridine-2 carboxaldehyde thiosemicarbazone. AB - Various substituted pyridine-2-carboxaldehyde thiosemicarbazones (12 compounds) have been synthesized and evaluated for antineoplastic activity in mice bearing the L1210 leukemia. Oxidation of 3-nitro-2-picoline,5-nitro-2-picoline,3-nitro 2,4-lutidine, and 5-nitro-2,4-lutidine with selenium dioxide was employed to generate the corresponding pyridine-2-carboxaldehydes, which were then converted to cyclic ethylene acetals and subsequently reduced to amino and hydroxyamino derivatives by catalytic hydrogenation. Condensation of nitro aldehydes and acetals with thiosemicarbazide afforded the respective thiosemicarbazones. Acetylation of the amino acetals and alkylsulfonation of the 5-amino acetal, followed by condensation with thiosemicarbazide was employed to yield amide thiosemicarbazones. The most active compounds synthesized were 3-aminopyridine-2 carboxaldehyde thiosemicarbazone and 3-amino-4-methylpyridine-2-carboxaldehyde thiosemicarbazone which produced against the L1210 leukemia, % T/C values of 246 and 255, and 40% 60-day long-term survivors at two daily doses of 40 mg/kg and 10 mg/kg, respectively, for six consecutive days. PMID- 1433179 TI - 5,10-Methylenetetrahydro-5-deazafolic acid and analogues: synthesis and biological activities. AB - The synthesis of 5,10-methylene-5-deazatetrahydrofolic acid (2), a stable, rigid analogue of 5,10-methylenetetrahydrofolate (1), is reported as a potential inhibitor of thymidylate synthase. The target compound was obtained by a Fisher indole type cyclization of the hydrazone 16 from 2-amino-6-hydrazino-4 oxopyrimidine (10) and diethyl N-[4-(3-formyl-1-pyrrolyl)benzoyl]-L-glutamate (15) followed by catalytic reduction of the product 17. Similarly, modification of the Fisher-indole type cyclization of the appropriate hydrazone precursors 11 and 12 afforded the nonclassical analogues 3-amino-7,8,9-trimethyl-2H pyrrolo[3',4':4,5]pyrido[2,3-d]pyrimidin-1- one (4) and 3-amino-8-benzyl-7,9 dimethyl-2H-pyrrolo[3',4':4,5]pyrido [2,3-d]pyrimidin-1-one (5), respectively. The target compound 2, its aromatic precursor 18, and the nonclassical analogue 4 were evaluated as inhibitors of the growth of Manca human lymphoma cells and also as inhibitors of human dihydrofolate reductase, human thymidylate synthase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. Compound 18 showed weak inhibition of lymphoma cell growth (IC50 = 42 microM) and of AICAR formylTF (IC50 = 17 microM). Compounds 2 and 4 did not inhibit lymphoma cell growth or thymidylate synthase. The inactivity of 2 was attributed to its lack of flexibility leading to its inability to bind to thymidylate synthase. PMID- 1433180 TI - Antimitotic agents: structure-activity studies with some pyridine derivatives. AB - Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent antimitotic agents. In the 5-nitropyridine series overall biological activity was reduced by replacement of the oxime moiety with a keto or alcohol group and by replacement of the 1-methyl group of the side chain with hydrogen. Reduction of the nitro group of the 5-nitropyridines containing an alcohol in the side chain to the corresponding 5-aminopyridines increased biological activity. Preliminary studies showed that the 5-nitropyridine oximes were considerably less potent than the pyridopyrazines as antimitotic agents and that the former are apparently not converted to the latter in vivo. The inhibition of the incorporation of pyrimidine nucleosides into DNA and RNA was identified as another possible mode of action of the 5-nitropyridine oximes. PMID- 1433181 TI - Novel 1,2,4-oxadiazoles and 1,2,4-thiadiazoles as dual 5-lipoxygenase and cyclooxygenase inhibitors. AB - A series of 1,2,4-oxadiazoles and 1,2,4-thiadiazoles containing a 2,6-di-tert butylphenol substituent were prepared and evaluated as dual inhibitors of 5 lipoxygenase and cyclooxygenase in rat basophilic leukemia (RBL-1) cells. Several of these compounds show oral efficacy in the rat carrageenan footpad edema (CFE) and mycobacterium footpad edema (MFE) antiinflammatory models, without concomitant gastric ulceration. Structure-activity relationships are discussed. The best compounds (ID40 values in MFE of 3-8 mg/kg po) contain guanidine-derived substituents on the heterocyclic ring. PMID- 1433182 TI - Conformational analysis of the aromatase inhibitor 3-ethyl-3-(4 pyridyl)piperidine-2,6-dione (rogletimide) and discovery of potent 5-alkyl derivatives. AB - Analysis of the proton NMR spectra of 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione (rogletimide, 1) shows that it exists in solution with the aromatic ring in an axial position; the same conformation was found for aminoglutethimide. Excess lithium diisopropylamide treatment of 1 formed a dianion which methylated at C-5. The major product with the methyl group trans to the pyridyl ring retained this ring in an axial position and had higher aromatase inhibitory potency than 1. The minor diastereoisomer with an equatorial pyridyl ring had low potency. Upon elongating the alkyl chain, particularly high inhibitory activity was found for the major product isomer having a C-5 octyl, coinciding with the high activity in C-3 and N-1 octyl derivatives of 1, but there was only a small difference in the activity between the enantiomers of 5-octyl-1 and activity was reduced rather than increased when octyl also replaced ethyl at C-3. The results partially support a previously described model comparing binding of androstenedione to aromatase in as much as an axial pyridyl ring is needed to mimic the axial C-19 methyl group of the steroid and bind to the heme component of the enzyme, but for the derivatives bearing a C-5 octyl, the function of the glutarimide ring seems to be simply as a spacer between the hydrophobic chain and the pyridyl ring. PMID- 1433183 TI - Aliphatic propargylamines: potent, selective, irreversible monoamine oxidase B inhibitors. AB - A series of aliphatic propargylamine derivatives has been synthesized. Some of them possess highly potent, irreversible, selective, inhibitory activity toward monoamine oxidase B (MAO-B). The potency of the inhibitors is related to chain length and substitution of a hydrogen on the terminal carbon of the aliphatic chain. MAO inhibitory activity as assessed in vitro increased as the aliphatic carbon chain length increased. Substitution of a hydrogen by hydroxyl, carboxyl, or carbethoxyl groups at the aliphatic chain terminal or replacement of the methyl group on the nitrogen atom by an ethyl group considerably reduced the inhibitory activity. Stereospecific effects were observed with the R-(-) enantiomer being 20-fold more active than the S-(+)-enantiomer. Inhibitors with relatively short carbon chain lengths (i.e. four to six carbons) were found to be more potent than those with longer chains in inhibiting brain MAO-B activity in vivo especially after oral administration. Chronic administration of low doses of the aliphatic propargylamines caused a slight cumulative inhibition of MAO-A activity in the mouse brain. These MAO-B inhibitors appear to be nontoxic, and they do not possess an amphetamine-like moiety in their structure as is the case for deprenyl. We expect that these aliphatic propargylamines may be useful in the treatment in certain neuropsychiatric disorders. PMID- 1433184 TI - Discovery of a novel class of orally active, non-peptide angiotensin II antagonists. PMID- 1433185 TI - (R)-2-(3-mercapto-2(S)-methyl-1-oxo-propoxy)-3-(methylthio)propanoic acid, the first ultra-short-acting angiotensin converting enzyme inhibitor. PMID- 1433186 TI - Special issue dedicated to Ralph F. Hirschmann. PMID- 1433187 TI - A general method for the preparation of internally quenched fluorogenic protease substrates using solid-phase peptide synthesis. AB - A general scheme for obtaining a fluorescent donor/acceptor peptide substrate via solid-phase synthesis methodology is presented. The key feature of this method is the design of a glutamic acid derivative that has been modified on the carboxyl side chain with a 5-[(2'-aminoethyl)-amino]naphthelenesulfonic acid (EDANS) to create a fluorescent donor moiety that can be incorporated near the C-terminus of the peptide substrate. The corresponding fluorescent acceptor group containing a 4-[[4-(dimethylamino)phenyl]azo]benzoic acid (DABCYL) can then be attached to the resin-bound peptide at the N-terminus while all side-chain groups are still fully protected. Substrates for renin and HIV proteinase are synthesized as examples. PMID- 1433188 TI - Inhibition of human leukocyte elastase. 4. Selection of a substituted cephalosporin (L-658,758) as a topical aerosol. AB - Human leukocyte elastase (HLE) is a serine protease which has been implicated as a causative agent in several pulmonary diseases. The continued modification of our previously reported cephalosporin-based HLE inhibitors has led to the identification of a series of C-2 amides with potent, topical activity in an in vivo hamster lung hemorrhage model. While the most potent in vitro HLE inhibition had previously been obtained with lipophilic ester derivatives, it was found that the less active, but more polar and stable, amide derivatives were much more effective in vivo. The development of the structure--activity relations for optimization of these activities is discussed. These results led to the selection of 3-(acetoxymethyl)-2-[(2(S)-carboxypyrrolidino)carbonyl]-7 alpha-methoxy-8-oxo 5-thia-1-azabicyclo[4.2.0]oct-2-ene, 5,5-dioxide (3, L-658,758) as a selective, potent, time-dependent HLE inhibitor suitable for formulation as a topical aerosol drug for possible clinical use. PMID- 1433189 TI - Orally active beta-lactam inhibitors of human leukocyte elastase-1. Activity of 3,3-diethyl-2-azetidinones. AB - A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic beta-lactam and the mechanism of beta-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE. This work led to the identification of 4-[(4-carboxyphenyl)-oxy]-3,3-diethyl-1- [[(phenylmethyl)amino]carbonyl]-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE). Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model. Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays. The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented. PMID- 1433190 TI - Highly potent, orally active diester macrocyclic human renin inhibitors. AB - Replacing one amide bond in macrocyclic renin inhibitors of the general structure 1 and 2 with an ester linkage gave glutamate-derived inhibitors 3 and serine derived inhibitors 4. While this oxygen-for-nitrogen exchange had little effect on potency in the glutamate series, potency was dramatically increased in the serine series. In this series, the 14-membered ring compounds proved to be more potent than the corresponding 13-membered ring derivatives. Substitution of the ring at the position corresponding to P2' generally increased potency. The absolute configuration at this center was shown to be R for the 4 morpholinomethyl derivative (4o), both by asymmetric synthesis and X-ray crystallography. Replacing the "Boc-Phe" moiety of inhibitor 4o with a variety of substituents led to subnanomolar inhibitors, one of which (the "3(S) quinuclidinyl-Phe" derivative 33) lowered blood pressure 20 mmHg and completely inhibited plasma renin activity for 6 h in sodium-depleted rhesus monkeys. This compound proved to have limited bioavailability (1% in rats) due to cleavage of the serine ester bond and rapid hepatic extraction. PMID- 1433191 TI - Analogs of Ac-CCK-7 incorporating dipeptide mimics in place of Met28-Gly29. AB - A series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met28-Gly29-Trp-Met-Asp- Phe-NH2, (1)] were prepared in which the Met28-Gly29 dipeptide was replaced by omega aminoalkanoic acids. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors, respectively, and for anorectic activity after intraperitoneal administration to rats. The analog incorporating 4-aminobutanoic acid (5) was only 8 times less potent than 1 in the pancreatic binding assay, was more potent in the striatal binding assay, and was more potent than 1 in reducing food intake in rats. Using a bioactive cyclic analog of Ac-CCK-7 as a template, several rigid spacers were designed and tested as substitutes for the Met28-Gly29 dipeptide. The analogs incorporating 3-aminobenzoic acid (20) and (1S)-trans-2 aminocyclopentanecarboxylic acid (26) proved highly effective in the binding assays and as anorectic agents. We hypothesize that for stimulation of CCK-A receptors, the main function of the N-terminal tripeptide of Ac-CCK-7 is to orient the tyrosine sulfate with respect to Trp30 and that the bioactive arrangement of these elements lies among those which are readily available to both 20 and 26. NOESY and distance-constrained molecular dynamics experiments carried out on 20 and 26 identified conformations in which the relative orientation of the tyrosine hydroxide and the alpha-carbon atom of tryptophan were similar, providing the basis for further drug design efforts. PMID- 1433192 TI - New hydroxyethylamine HIV protease inhibitors that suppress viral replication. AB - The synthesis of analogues of AcSerLeuAsn[Phe-HEA-Pro]IleValOMe (1, JG-365; where HEA stands for the hydroxyethylamine unit 2), a tight-binding inhibitor of HIVP, are reported. Systematic modification of the P3 and P3' regions of the inhibitors has led to smaller HIVP inhibitors that inhibit viral replication in HIV-infected and SIV-infected cell cultures. Six aliphatic and/or aromatic derivatives were prepared by replacing residues in the P3 regions of BocLeuAsn[Phe-HEA Pro]IleValOMe. Aromatic side chains at P3 gave better inhibitors than aliphatic side chains. The better inhibitors in this series contained a beta naphthylalanine or a biphenyl unit at P3. A second series of HIVP inhibitors were obtained by converting the P3 group into acyl groups. CbzAsn[Phe-HEA Pro]IlePheOMe and Qua-Asn-[Phe-HEA-Pro]-Ile-Phe-OMe (where Qua = quinolin-2 ylcarbonyl) are potent HIVP inhibitors with Ki values equal to 1.0 and 0.1 nM, respectively. The inhibition constants were determined by using the continuous fluorometric assay developed by Toth and Marshall. The activities of the protease inhibitors for inhibition of SIV replication were determined in vitro using CEM x 174 cells. Inhibition of HIV infection was determined essentially as reported by Pauwels and co-workers. The anti-HIV assay was carried out in culture using CEM cells (a CD4+ lymphocyte line) infected with virus strain HTLV-IIIb with a multiplicity of infection of 0.1. Several analogues inhibited the cytopathic effect at concentrations of 0.1-0.8 microgram/mL. These results establish that good inhibitors of HIV protease that inhibit viral replication in infected lymphocytes in in vitro cell assays can be obtained from JG-365 when the AcSerLeu unit is replaced by aromatic acyl derivatives. PMID- 1433193 TI - 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 9. The synthesis and biological evaluation of novel simvastatin analogs. AB - Substitution of hydroxy and hydroxyalkyl functionality at C-7 of the hexahydronaphthalene nucleus of simvastatin has provided novel analogs. The synthetic strategy employed epoxidation or Lewis acid-catalyzed aldol reaction of the 8-keto silyl enol ether as a key reactive intermediate. These analogs were evaluated as potential hypocholesterolemic agents via initial determination of their ability to inhibit HMG-CoA reductase in vitro. Oral activity of these compounds was determined in an acute rat model and a three-week study in cholestyramine-primed dogs. Compounds were identified that possessed in vitro and in vivo activity comparable to that of simvastatin. PMID- 1433195 TI - Imidazole-5-acrylic acids: potent nonpeptide angiotensin II receptor antagonists designed using a novel peptide pharmacophore model. AB - A series of novel nonpeptide angiotensin II receptor antagonists containing a substituted (E)-acrylic acid has been developed. The overlay of 1, an imidazole-5 acetic acid found in the patent literature, on a novel pharmacophore model of AII suggested that extension of the acid side chain and attachment of a second aryl residue to mimic the C-terminal phenylalanine region of AII would lead to increased activity. A study of extended acid side chains at C-5 of the imidazole nucleus led to the discovery of the (E)-acrylic acid 5 as a promising starting point for further exploration. As predicted by the modeling, substitution of a benzyl group on the acrylic acid side chain to mimic the phenylalanine gave increased potency. An extensive study of the SAR of the newly introduced aromatic ring revealed that electron-rich heteroaryl rings provided improved activity, most notably in the in vivo rat models. Compound 40, (E)-3-[2-butyl-1- [(2 chlorophenyl)methyl]imidazol-5-yl]-2-[(2-thienyl)methyl]-2- propenoic acid, has been shown to be a potent, competitive, and orally active small molecule AT-1 receptor antagonist. It exhibits a 2 orders of magnitude increase in binding affinity and a 10-fold improvement in in vivo potency as compared to compound 1 and represents an important milestone in the development of even more potent nonpeptide angiotensin II receptor antagonists. PMID- 1433194 TI - 4-substituted thiophene- and furan-2-sulfonamides as topical carbonic anhydrase inhibitors. AB - A series of 4-substituted thiophene- and furan-2-sulfonamides was prepared and was found to possess nanomolar-level potency for inhibition of human carbonic anhydrase II in vitro. Selected examples from this group were further evaluated for their potential to act as topically effective ocular hypotensive agents in the ocular normotensive albino rabbit and the ocular alpha-chymotrypsinized rabbit. Solubility studies in water and pH 7.4 buffer were carried out to estimate the ability of compounds to be formulated in solution. The sensitization potential of key representative structures was determined by in vitro glutathione reactivity studies and guinea pig maximization testing. PMID- 1433196 TI - Synthesis and biological activity of 13-epi-avermectins: potent anthelmintic agents with an increased margin of safety. AB - Chemical conversion of the potent anthelmintic natural products avermectin B1 (1) and avermectin B2 (3) to the corresponding 13-epi analogs (15 and 9) is described. The novel analogs retain the full potency of the natural products but are substantially safer. PMID- 1433197 TI - Affinity probes for the avermectin binding proteins. AB - The design and synthesis of a series of avermectin affinity probes used in the identification and purification of the avermectin binding proteins is described. These modified avermectins fall into two design classes: ligands to covalently modify specific avermectin binding proteins [an 125I-labeled aryl azide photoprobe (15) and a tritiated aziridine analog (6)] and ligands for affinity chromatography applications [three biotinylated compounds (10, 12, and 13) and one resin-bound derivative (9)]. The binding affinities of these compounds for the Caenorhabditis elegans avermectin binding protein is presented as well as their biological activities against C. elegans and Artemia salina. PMID- 1433198 TI - Differences in hydration and association of helical Boc-Val-Ala-Leu-Aib-Val-Ala Leu-(Val-Ala-Leu-Aib)2-OMe.xH2O in two crystalline polymorphs. AB - The 15-residue apolar peptide, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-(Val-Ala-Leu-Aib)2 OMe has been crystallized from 2-propanol-water (form I). The crystal parameters for I are as follows: C74H133N15O18.2H2O, space group P2(1), a = 9.185 (6) A, b = 47.410 (3) A, c = 10.325 (9) A, beta = 91.47 (2) degrees, Z = 2, R = 6.3% for 4532 reflections observed > 3 sigma (F), resolution 0.94 A. The structure is almost completely alpha-helical with eleven 5-->1 hydrogen bonds and one 4-->1 hydrogen bond near the N-terminus. The structure has been compared with a polymorph (form II) obtained from methanol-water (Karle, I. L.; Flippen-Anderson, J. L.; Uma, K.; Sukumar, M.; Balaram, P., J. Am. Chem. Soc. 1990, 112, 9350 9356). The two forms differ in the extent of hydration; form I contains two water molecules in the head-to-tail region of helical columns, while form II is more extensively solvated, with the equivalent of 7.5 water molecules. The three dimensional packing of helices is completely parallel in I and antiparallel in II. PMID- 1433199 TI - Stabilization of the N-terminal residues of luteinizing hormone-releasing hormone agonists and the effect on pharmacokinetics. AB - To stabilize leuprolide (1) against chymotrypsin and intestinal degradation several agonists of LHRH (2-12), modified at position 1, 2, or 3 and/or containing N-alpha-methyl at positions 1, 2, or 4, were synthesized by SPPS. These agonists were tested in vitro for (a) rat pituitary LHRH receptor binding, (b) LH release from rat pituitary cells, (c) stability against chymotrypsin, and (d) stability against rat intestinal degradation. The clearances of the compounds in the rat were determined using a RIA. Complete stabilization against chymotrypsin (t1/2) and lumenal degradation (T1/2) was achieved with substitution of NMe-Ser4 in leuprolide; however, with an increase in clearance. Substitution with 1-Nal3 increased both t1/2 and T1/2, while substitution with NAc-Sar1 increased only T1/2. [NAcSar1,NMeSer4,D-Trp6,Pro9NHEt]LHRH (12), the doubly stabilized analogue, was tested in the rat by both iv and id administrations, and its bioavailabilities were measured. No significant improvement in id absorption over leuprolide was observed. PMID- 1433200 TI - Potent V2/V1a vasopressin antagonists with C-terminal ethylenediamine-linked retro-amino acids. AB - We report the solid-phase synthesis and antagonistic potencies of 25 analogues (1 25) of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-ethyl-D tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-Tyr(Et)2-VAVP) (A) and of the related Ile4 (D) and [D-Phe2,Ile4] (E) analogues, potent antagonists of the antidiuretic (V2-receptor) and of the vasopressor (V1a-receptor) responses to arginine-vasopressin (AVP). Six of these peptides (1, 13, 17, 19, 21, and 23) have the Pro-Arg-Gly-NH2 tripeptide side chain fully or partially replaced or extended by ethylenediamine (Eda). The remaining 19 peptides have L- or D-amino acids retrolinked to these six C-terminal Eda peptides. Peptides 1, 13, 17, and 19 all have the ring structure of (A). Their side-chain structures are as follows: 1, Eda; 13, Pro-Eda; 17, Pro-Arg-Eda; 19, Arg-Gly-Eda. Peptide 21 is the Pro-Arg-Eda analogue of D; peptide 23 is the Pro-Arg-Gly-Eda analogue of E. Peptide 2 is the retro-Arg analogue of 1. Its side-chain structure is Eda<--Arg. Peptides 3-6 are analogues of 2 which have the D-Tyr-(Et)2 residue replaced by L Tyr(Et)2 (3), D-Phe2 (4), D-Ile2 (5), or D-Leu2 (6), respectively. Peptides 7-12 are analogues of 2 which have the C-terminal retro-Arg replaced in retrofashion by D-Arg (7), Gly (8), Orn (9), D-Orn (10), D-Lys (11), or Arg-Arg (12). Peptides 14-16 have D-Orn (14), D-Lys (15), and D-Arg (16) retrosubstituted to peptide 13. Peptides 18, 20, and 22 are the retro-Arg-substituted analogues of 17, 19, and 21, respectively. Peptides 24 and 25 have Val and D-Val in retrolinkage with 23, respectively. All 25 peptides were examined for agonistic and antagonistic potencies in AVP V2/V1a assays. With the exception of peptides 5 and 6, all exhibit potent anti-V1a antagonism, with anti-V1a pA2 values in the range 7.64 8.33.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1433201 TI - Growth hormone-releasing factor analogs with hydrophobic residues at position 19. Effects on growth hormone releasing activity in vitro and in vivo, stability in blood plasma in vitro, and secondary structure. AB - To test the hypothesis that replacing Ala19 in growth hormone-releasing factor (GRF) with more hydrophobic residues will increase growth hormone releasing activity, four GRF analogs were prepared and tested. The molecules were made by substituting Val, Ile, or Leu at position 19 of [Thr2,Ala15,Leu27]bGRF(1-29)NH2. The compounds were evaluated for growth hormone (GH) releasing activity in vitro (rat anterior pituitary cells) and in vivo (steers). Additionally, their half life in vitro was determined in bovine plasma, and their secondary structure was examined by circular dichroism. In pituitary cells, peptides with substitutions at position 19 had the following potencies: Ala (native), 0.37; Val, 1.16; Ile, 0.37; Leu, 0.043. When assayed in steers as a single iv bolus, over a 2-h period, the compounds gave the following integrated GH response: Ala, 2.75; Val, 2.67; Ile, 2.57; Leu, 1.55. Only the Leu analog was statistically different from the other three (p = 0.05). In bovine plasma, the half-lives (hours) were as follows: Ala, 4.9; Val, 6.6; Ile, 12.3; Leu, 14.7. In phosphate buffer the compounds were calculated to have the following percent helical content: Ala, 26; Val, 21; Ile, 27; Leu, 32. For these analogs, helicity in aqueous buffer is inversely related to their in vitro activity. Using a linear multiple regression model, the plasma half-life of the analogs positively correlated (r2 = 0.999) with both the hydrophobicity of the residue at position 19 and the helicity of the analog. Although the Val analog had both increased inherent activity and increased plasma stability in vitro compared to the Ala analog, in this study we were unable to demonstrate an increase in activity in vivo. The in vivo GH releasing activity of the analogs was not simply related to a combination of their intrinsic GH releasing activity and their in vitro plasma half-life. This suggests that in vivo additional factors are moderating the expression of activity. PMID- 1433202 TI - Enzymatic semisynthesis of a superpotent analog of human growth hormone-releasing factor. AB - A superpotent analog of human growth hormone-releasing factor, [desNH2Tyr1,D Ala2,Ala15]-GRF(1-29)-NH2 (4), was prepared from the precursor, [Ala15,29]-GRF(4 29)-OH (1), by a two-step enzymatic semisynthesis. The amidated C-terminus, essential for high biological potency, was obtained via a carboxypeptidase Y catalyzed exchange of Ala29-OH for Arg29-NH2 to produce [Ala15]-GRF(4-29)-NH2 (2). The N-terminal desNH2Tyr-D-Ala moiety, which greatly increases in vivo duration of action, was then incorporated by V8 protease-catalyzed condensation of segment 2 with desNH2Tyr-D-Ala-Asp(OH)-OR [R = CH3CH2- (3a) or 4-NO2C6H4CH2 (3b)]. The main focus of this report was to develop conditions to use the V8 protease-catalyzed coupling while avoiding a competing cleavage of the proteolytically-sensitive Asp25-Ile26 bond in GRF. Conversion of 2 to 4 in couplings employing the alpha-ethyl ester of the acyl component 3a was limited to about 60% by competing proteolysis at Asp25-Ile26. This system was adequate for preparing, isolating, and fully characterizing the target analog 4 and identifying the side products. The 4-nitrobenzyl ester 3b proved to be a superior substrate, resulting in 90% conversion of 2 to 4 with no detectable loss to proteolysis and requiring significantly lesser amounts of catalyst. These results demonstrate that enzymatic semisynthesis of a biologically-active peptide amide which contains unnatural amino acids at the N-terminus can be achieved from a biosynthetic precursor in good yield and purity. PMID- 1433203 TI - Investigation of conformational specificity at GPIIb/IIIa: evaluation of conformationally constrained RGD peptides. AB - RGD-containing proteins and peptides are known to bind to the platelet GPIIb/IIIa receptor and inhibit platelet aggregation. That a conformational component to the specificity exists is suggested by significantly lower activity of linear RGD analogs relative to closely related cyclic peptides and small proteins containing the RGD sequence. Recently, conformations for a suite of RGD containing cyclic peptides have been defined by NMR-based methods and, for one molecule, by X-ray diffraction. We report here the NMR-based conformational analysis of an additional cyclic peptide, cyclo(Pro-Arg-Gly-Asp-D-Pro-Gly), and compare the conformational variations in the suite of peptides and related analogs. Biological activity data for these peptides shows a preference of the platelet GPIIb/IIIa receptor for one conformation of the RGD sequence, but suggests its ability to bind a second, distinct conformation. PMID- 1433204 TI - Design and synthesis of a C7 mimetic for the predicted gamma-turn conformation found in several constrained RGD antagonists. PMID- 1433205 TI - 4-Oxospiro[benzopyran-2,4'-piperidines] as class III antiarrhythmic agents. Pharmacological studies on 3,4-dihydro-1'-[2-(benzofurazan-5-yl)- ethyl]-6 methanesulfonamidospiro[(2H)-1-benzopyran-2,4'-piperidin]-4-on e (L-691,121). PMID- 1433206 TI - N-substituted pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides. A new class of diuretics. AB - The synthesis and evaluation of a new class of diuretic agents derived from the pyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide ring system are described. Preliminary structure-activity relationships indicate that the nature and location of the substituents at different positions of the heterocycle are crucial for activity. Thus, a novel synthetic methodology has been developed to selectively introduce the desired substituents at different positions. From the study of the pharmacological properties (dose-response curves, duration of action, and acute toxicity) of the most active compounds, 4-amino-1,7-diethyl-6 methylpyrazino[2,3-c][1,2,6]thiadiazine++ + 2,2-dioxide (9) was selected for further investigation. Compound 9 (C10H15N5O2S) crystallizes in space group P21/a with unit cell dimensions a = 16.482 (1), b = 9.3484 (3), c = 8.333 (3) A, beta = 103.003 (3) degrees, Z = 4. PMID- 1433207 TI - 6-Hydroxy-3-n-propyl-2,3,4,5-tetrahydro-1H-3-benzazepine and analogs: new centrally acting 5-HT1A receptor agonists. AB - The ring-closed phenylethylamine analogue 6-hydroxy-3-n-propyl-2,3,4,5-tetrahydro 1H-3-benzazepine (1) is a 5-HT1A receptor agonist of moderate potency, according to both in vivo biochemical data and in vitro binding data. The active compounds of this series also induce the 5-HT behavioral syndrome. Molecular modeling studies were performed with molecular mechanics calculations, and a tentative explanation for the relatively low potency of these serotonergic benzazepines is provided. PMID- 1433208 TI - Synthesis and biological evaluation of 5'-sulfamoylated purinyl carbocyclic nucleosides. AB - The first series of 5'-sulfamoylated carbocyclic purinyl nucleosides was synthesized and tested for antitumor and antibacterial activities. The target compounds were formed by reacting the 2',3'-acetonide-protected carbocyclic nucleosides with sulfamoyl chloride, followed by deprotection. The agents were tested for cytotoxic activity against P388 mouse leukemia cells. Two compounds, 5'-sulfamoyl carbocyclic adenosine (2) and 5-sulfamoyl-8-aza carbocyclic adenosine (6) exhibited IC50 values as low as 62 and 15 nM, respectively. These analogs inhibited protein biosynthesis and slowed down DNA and RNA biosyntheses in the P388 cells. None of the target molecules were as potent against Escherichia coli as they were against the tumor cells. Also, in cell-free systems, agents 2 and 6 were more effective inhibitors of protein synthesis in rabbit reticulocyte lysate than in E. coli. These new carbocyclic derivatives appear to be somewhat selective for eukaryotic over prokaryotic cells in affecting translation. PMID- 1433210 TI - New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4 (biphenylylmethoxy)quinoline derivatives. AB - A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.01-1 microM. Structure activity studies showed the quinoline nitrogen atom and a short alkyl chain at the quinoline 2-position to be essential for receptor binding. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-2.0 mg/kg. One of the compounds, 2-ethyl-4-[[2'-(1H-tetrazol-5-yl)biphenyl-4 yl]methoxy]quinoline (5g), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg in AII-infused, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model, compound 5g showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg. On the basis of its profile, this compound, designated ICI D8731, has been selected for clinical evaluation. PMID- 1433209 TI - Novel functional M1 selective muscarinic agonists. 2. Synthesis and structure activity relationships of 3-pyrazinyl-1,2,5,6-tetrahydro-1-methylpyridines. Construction of a molecular model for the M1 pharmacophore. AB - A series of 3-(3-substituted-pyrazinyl)-1,2,5,6-tetrahydro-1-methylpyridines were synthesized and found to have high affinity for central muscarinic receptors. The ability of some of these compounds to inhibit the electrically stimulated twitch of the guinea pig vas deferens indicated that the compounds were M1 agonists. M1 agonist activity was related to the length of the side chain attached to the pyrazine ring, with maximal activity being obtained with the hexyloxy side chain. The (hexyloxy)pyrazine 3f lacked M2 agonist activity as it failed to affect the guinea pig atria and was also relatively devoid of M3 agonist activity as determined by its lack of tremorogenic and sialogogic effects in mice. A comparison of the M1 agonist efficacy of these pyrazines and related 1,2,5 thiadiazoles and 1,2,5-oxadiazoles suggested that M1 efficacy was related to the magnitude of electrostatic potential located over the nitrogens of the respective heterocycles. The heteroatom directly attached to the 3 position of the pyrazine or 1,2,5-thiadiazole heterocycle markedly influenced the M1 efficacy of the compounds by determining the energetically favorably conformers for rotation about the bond connecting the tetrahydropyridyl ring and the heterocycle. A three dimensional model for the M1-activating pharmacophore was proposed based on computational studies and the model of the muscarinic pharmacophore proposed by Schulman. PMID- 1433211 TI - Synthesis and antibacterial activity of a series of basic amides of teicoplanin and deglucoteicoplanin with polyamines. AB - Basic carboxamides of teicoplanin A2 (CTA) and its aglycon (TD) are prepared by condensation of the 63-carboxyl function of these antibiotics with linear or branched polyamines. The antimicrobial activities of some of the resulting compounds were better than those of the unmodified antibiotics. The presence of more than one basic group in the amidic chain enhanced the in vitro activity of some TD-amides against Gram-negative bacteria; two of these derivatives were also effective in vivo against Escherichia coli septicemia in the mouse. Among the CTA derivatives, the amide with spermine showed some unexpected in vitro activity against Gram-negatives. Both CTA- and TD-amides with polyamines are very soluble in water over a wide range of pH and are very hydrophilic. PMID- 1433212 TI - Synthesis, chemical, and biological properties of vinylogous hydroxamic acids: dual inhibitors of 5-lipoxygenase and IL-1 biosynthesis. AB - Vinylogous hydroxamic acids (3-(N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents. The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described. The VHAs were prepared by condensation of the appropriate N substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C). The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH. VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides. VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade. They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron. PMID- 1433214 TI - Inhibition of hog liver folylpolyglutamate synthetase by 5-substituted 5,8 dideaza analogues of folic acid bearing a terminal L-ornithine residue. AB - Five new N alpha-(5,8-dideazapteroyl)-L-ornithines have been prepared using multistep synthetic sequences. These include N alpha-[5-(trifluoromethyl)-5,8 dideazapteroyl]-L-ornithine, 3, as well as N alpha-[5-(trifluoromethyl)-5,8 dideazaisopteroyl]-L-ornithine, 4, and its 5-fluoro and 5-chloro analogues. Both of the compounds containing a 5-(trifluoromethyl) group (3 and 4) were found to be excellent inhibitors of homogeneous hog liver folylpolyglutamate synthetase, having Ki values in the same range as N alpha-(5-chloro-5,8-dideazapteroyl)-L ornithine, 2, (approximately 10 nM). However, the bridge-reversed isomer of 2 was 60-fold less inhibitory than 2. PMID- 1433213 TI - Copyrine alkaloids: synthesis, spectroscopic characterization, and antimycotic/antimycobacterial activity of A- and B-ring-functionalized sampangines. AB - Several A- and B-ring-substituted sampangines were synthesized and evaluated for antifungal and antimycobacterial activity against AIDS-related opportunistic infection pathogens. Electrophilic halogenation provided a channel for structural elaboration of the sampangine B-ring at position 4, while the synthesis of A-ring 3-substituted sampangines and benzo[4,5]sampangine (24) were achieved from the corresponding functionalized cleistopholines. Two-dimensional NMR spectroscopy was used to rigorously characterize the A- and B-ring substituent patterns. Structure-activity relationship studies revealed the activity of the sampangines was enhanced by the presence of a substituent at position 3 or by a 4,5-benzo group. PMID- 1433215 TI - (Pyridylcyanomethyl)piperazines as orally active PAF antagonists. AB - A series of (pyridylcyanomethyl)piperazines was prepared and evaluated for PAF antagonist activity. Compounds were tested in vitro in a PAF-induced platelet aggregation assay and in vivo in a PAF-induced hypotension test in normotensive rats. Oral activity was ascertained through a PAF-induced mortality test in mice. The main structure-activity trends of the series were established. Activity was mainly found in four skeletons: 1-acyl-4-(3-pyridylcyanomethyl)piperazine, 1-acyl 4-(4-pyridylcyanomethyl)piperazine, 1-acyl-4-(3-pyridylcyanomethyl)piperidine, and 1-acyl-4-cyano-4-(3-pyridylamino)piperidine. The acyl substituents, diphenylacetyl and 3,3-diphenylpropionyl, provided the most active compounds, and the introduction of an amine or hydroxy group in the 3,3-diphenylpropionyl substituent led to further improvement in oral activity. As a result, three of the most active compounds (100, 114, and 115) have been selected for further pharmacological development. PMID- 1433216 TI - Synthesis and evaluation of 3-substituted 17-methylmorphinan analogs as potential anticonvulsant agents. AB - Dextromethorphan (1,(+)-3-methoxy-17-methylmorphinan) demonstrates anticonvulsant activity in a variety of in vitro and in vivo models of convulsive action. It is well known that 1 is metabolized to its phenolic derivative dextrorphan (2) and this metabolite is also a potent anticonvulsant. A series of (+)-3-substituted-17 methylmorphinans, which are structurally similar to 1 but are either not expected to be metabolized to 2 or might do so at a reduced rate, as compared to 1, were prepared. Three analogs, 5 ((+)-3-amino-17-methylmorphinan), 14 ((+)-3-ethoxy-17 methylmorphinan), and 15 ((+)-3-(2-propoxy)-17-methylmorphinan) were found to possess potent anticonvulsant activity with full efficacy (ED50 25, 5.6, and 3.9 mg/kg, sc, respectively) in the rat supramaximal electroshock (MES) test. Binding potencies of these compounds to receptor sites labeled with [3H]dextromethorphan ([3H]1), in rat brain and guinea pig brain subcellular fractions, and [3H]thienylcyclohexylpiperidine (TCP) and [3H]glycine in rat brain, were determined. Most of the analogs displaced [3H]1 from its binding sites, with compounds 14 (IC50 0.42 microM) and 15 (IC50 0.88 microM) having equivalent potencies to 1 (IC50 0.59 microM), in rat brain, and no appreciable activity at the [3H]TCP or [3H]glycine-labeled sites. Compound 5 did not bind with appreciable activity to the [3H]1 site, in rat brain, but did bind to the [3H]TCP site with lower potency than the parent 1 (IC50 7.8 and 2.0 microM, respectively). The mechanism of anticonvulsant action of these agents is not clear although it appears that interaction at the [3H]1 sites may be involved. PMID- 1433218 TI - Guanidinophenyl-substituted enol lactones as selective, mechanism-based inhibitors of trypsin-like serine proteases. AB - We have synthesized four guanidinophenyl-substituted protio enol and iodo enol lactones (3-(4-guanidinophenyl)-6-methylidenetetrahydro-2-pyranone (1), 3-(4 guanidinophenyl)-6-(E)-(iodomethylidene)tetrahydro-2-pyran one (2), 4-(4 guanidinophenyl)-6-methylidenetetrahydro-2-pyranone+ ++ (3), and 4-(4 guanidinophenyl)-6-(E)-(iodomethylidene)tetrahydro-2-pyran one (4)) and tested them for inhibitory activity against some trypsin-like enzymes, namely trypsin, urokinase, tissue plasminogen activator (t-PA), plasmin, and thrombin, as well as alpha-chymotrypsin and human neutrophil elastase (HNE). The beta-aryl-substituted protio lactone 3 was a potent alternate substrate inhibitor of trypsin and urokinase. The alpha-aryl-substituted iodo lactone 2 was a permanent inactivator of urokinase, plasmin, t-PA, thrombin, and alpha-chymotrypsin, exhibiting a relatively high specificity for the former two enzymes. In general, these compounds showed a preference for inactivating trypsin-like enzymes over alpha chymotrypsin and HNE. Also, within the class of trypsin-like enzymes, there was generally good selectivity of inhibition. PMID- 1433217 TI - Synthesis and biological activity of N6-(p-sulfophenyl)alkyl and N6-sulfoalkyl derivatives of adenosine: water-soluble and peripherally selective adenosine agonists. AB - A series of N6-(p-sulfophenyl)alkyl and N6-sulfoalkyl derivatives of adenosine was synthesized, revealing that N6-(p-sulfophenyl)adenosine (10b) is a moderately potent (Ki vs [3H]PIA in rat cortical membranes was 74nM) and A1-selective (120 fold) adenosine agonist, of exceptional aqueous solubility of > 1.5 g/mL (approximately 3 M). Compound 10b was very potent in inhibiting synaptic potentials in gerbil hippocampal slices with an IC50 of 63 nM. At a dose of 0.1 mg/kg ip in rats, 10b inhibited lipolysis (a peripheral A1 effect) by 85% after 1 h. This in vivo effect was reversed using the peripherally selective A1 antagonist 1,3-dipropyl-8-[p-(carboxyethynyl)phenyl]xanthine (BW1433). The same dose of 10b in NIH Swiss mice (ip) was nearly inactive in locomotor depression, an effect that has been shown to be centrally mediated when elicited by lower doses of other potent adenosine agonists, such as N6-cyclohexyladenosine (CHA) (Nikodijevic et al. FEBS Lett. 1990, 261, 67). HPLC studies of biodistribution of a closely related and less potent homologue, N6-[4-(p-sulfophenyl)butyl]adenosine indicated that a 25 mg/kg ip dose in mice resulted in a plasma concentration after 30 min of 0.46 micrograms/mL and no detectable drug in the brain (detection limit < 0.1% of plasma level). Although 10b at doses > 0.1 mg/kg in mice depressed locomotor activity, this depression was unlike the effects of CHA and was reversible by BW1433. These data suggest that 10b is a potent adenosine agonist in vivo and shows poor CNS penetration. PMID- 1433219 TI - Synthesis of novel MPTP analogs as potential monoamine oxidase B (MAO-B) inhibitors. AB - The nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetahydropyridine (MPTP) is an excellent substrate and a weak inactivator of the flavoenzyme monoamine oxidase B (MAO-B). In an attempt to develop novel mechanism-based inactivators of MAO-B, we have synthesized analogs of MPTP bearing a variety of functional groups at either the N or the C(4) position and have examined their interactions with a purified MAO-B preparation isolated from beef liver. The substituents selected include allyl, propargyl, ethenyl, ethynyl, and cyclobutyl, that is, functionalities which were considered potential sources of enzyme generated electrophilic or radical intermediates that might alkylate and inactivate the enzyme. None of the C(4)-substituted compounds displayed significant enzyme inhibitor properties although some proved to be good substrates. In the N-substituted MPTP series only the 4-phenyl-1-propargyl analog was a good inhibitor. The time- and concentration dependent inhibition of MAO-B displayed by this compound is consistent with a mechanism-based inactivation pathway and the catalytic mechanism currently held for monoamine oxidases. The results of these studies provide additional insights into the steric features of the active site of MAO-B and predict that the area in which the C(4) substituent of the tetrahydropyridine ring resides lacks a reactive nucleophilic group. PMID- 1433220 TI - Adenosine deaminase inhibitors. Synthesis and biological evaluation of C1' and nor-C1' derivatives of (+)-erythro-9-(2(S)-hydroxy-3(R)-nonyl)adenine. AB - The synthesis of various chiral derivatives of (+)-erythro-9-(2-hydroxy-3 nonyl)adenine, (+)-EHNA, from (2S,3R)-3-amino-1,2-O-isopropylidene-1,2-nonanediol by condensation with 5-amino-4,6-dichloropyrimidine is described. The compounds synthesized were C1'- and nor-C1'-(+)-EHNA derivatives. When tested with calf spleen ADA, C1'-OH- and nor-C1'-(+)-EHNA had comparable inhibitory activity that was 1 order of magnitude lower than that of (+)-EHNA. Potency was reduced further in nor-C1' derivatives. PMID- 1433221 TI - Synthesis and conformational properties of the lanthionine-bridged opioid peptide [D-AlaL2,AlaL5]enkephalin as determined by NMR and computer simulations. AB - We report the synthesis and conformational analysis by means of NMR and computer simulations of a novel opioid peptide with the sequence [formula: see text], which we write as [formula: see text], abbreviated [D-AlaL2,L-AlaL5]EA, where AlaL denotes each of the lanthionine amino acid ends linked by a monosulfide bridge and EA indicates enkephalinamide. Data from 2D NMR (HOHAHA and ROESY) provide short-range NOEs that are used as constraints in molecular modeling; measurement of coupling constants shows that chi 1 (D-AlaL2) is predominantly in either the t or g- conformation, and temperature coefficient data suggest the participation of the AlaL5 amide proton in an intramolecular hydrogen bond. The use of NOE and hydrogen-bond constraints in a distance-geometry program yields a large number of initial conformations compatible with the data. Energy minimization of these structures using CHARMM results in three families of backbone ring conformations, labled A1, A2, and B. The torsion chi 1 in D-AlaL2 remains close to trans for all three conformations. Molecular dynamics in vacuo at 300 K show that these three families of conformers interconvert, with concerted shifts in two of the three torsions psi(Phe), phi(AlaL5), and chi(AlaL5). The [D-AlaL2,L-AlaL5]EA is superactive in the guinea pig ileum (GPI) and mouse vas deferens (MVD) in vitro tests and also in the rat hot plate test in vivo. At the same time, this analog with a constrained 13-membered ring shows virtually no selectivity with a ratio IC50 (MVD)/IC50 (GPI) of 0.882. PMID- 1433222 TI - Fluoronaphthyridines and -quinolones as antibacterial agents. 5. Synthesis and antimicrobial activity of chiral 1-tert-butyl-6-fluoro-7-substituted naphthyridones. AB - A series of novel 7-substituted-1-tert-butyl-6-fluoronaphthyridone-3- carboxylic acids has been prepared. These derivatives are characterized by chiral aminopyrrolidine substituents at the 7 position. In this paper we report the full details of the asymmetric synthesis of this series of compounds. Structure activity relationship studies indicate that the absolute stereochemistry at the asymmetric centers of the pyrrolidine ring is critical for maintaining good activity. Compounds 60 and 61 (3-amino-4-methylpyrrolidine enantiomers) were selected for preclinical evaluation. PMID- 1433223 TI - Isobenzofurans as conformationally constrained miconazole analogues with improved antifungal potency. AB - A series of halogen-substituted isobenzofuran analogues was synthesized, which represented conformationally constrained analogues of miconazole (1). In vitro and in vivo topical antifungal activity against both dermatophytes and Candida species varied widely, but 13c proved to be significantly superior to both 1 and clotrimazole against a vaginal Candida infection in hamsters, while 13b was significantly more active than 1 against a a topical Trichophyton infection in guinea pigs. None of the compounds were orally active. When the most direct analogue of 1 proved to be among the least active, a molecular modeling study was done using 1, the two active analogues 13b and 13c, and the inactive analogue 13a. All four compounds possessed skeletally similar conformations either at or energetically readily accessible from the global minimum energy conformations. This common conformation of the inactive analogue 13a, however, occupies unique molecular volume space associated with two chlorine atoms, which must also present unique electrostatic properties at the receptor. The conformation activity relationships discussed may contribute toward deduction of additional structural requirements for pharmacophore optimization and more efficacious antifungal drugs. PMID- 1433224 TI - Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake. AB - The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of < 1 microM (including 5, Table I; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans. PMID- 1433225 TI - Analogs of CCK incorporating conformationally constrained replacements for Asp32. PMID- 1433226 TI - The mapping of a gene for craniosynostosis: evidence for linkage of the Saethre Chotzen syndrome to distal chromosome 7p. AB - Craniosynostosis or premature closure of the cranial sutures is a common abnormality occurring in about 1 in 2500 children. There is evidence of mendelian inheritance in some 20% of cases. Published reports of patients with structural alterations of the short arm of chromosome 7 have suggested that two or more genes for craniosynostosis may be situated in this region. The Saethre-Chotzen syndrome (acrocephalosyndactyly type III) is one of the most common autosomal dominant craniosynostosis syndromes. Results of molecular genetic linkage studies provide evidence for localisation of the gene responsible to distal chromosome 7p. PMID- 1433227 TI - Screening and genetic counselling for relatives of patients with breast cancer in a family cancer clinic. AB - Family history is the major risk factor in the aetiology of breast cancer. Breast screening is currently available to women from the age of 50 to 64 through the National Breast Screening Programme. There is, however, an equivalent risk of developing breast cancer below 50 for first degree relatives of women diagnosed with breast cancer premenopausally. We have estimated the risk of breast cancer for relatives of women affected at different ages and used these to establish a family cancer clinic offering breast screening based on individual risk. In three years we have seen 851 patients. Compliance for annual radiology was in excess of 83% over this period and of five cancers detected one had a lump at presentation, two developed interval breast lumps, and two were asymptomatic. PMID- 1433228 TI - A non-isotopic in situ hybridisation study of the chromosomal origin of 15 supernumerary marker chromosomes in man. AB - Fifteen patients presenting with mosaic or non-mosaic karyotypes containing a distamycin-DAPI negative de novo or familial supernumerary marker chromosome were studied with non-isotopic in situ hybridisation using a library of alphoid centromere specific and satellite II/III probes. The in situ hybridisation studies showed that seven markers were derived from satellited autosomes (three chromosome 13/21, two chromosome 14, two chromosome 22), six from non-satellited autosomes (two chromosome 4, one chromosome 12, one chromosome 16, two chromosome 19), and one from the Y chromosome. One non-mosaic marker was negative for all the alphoid and satellite II/III probes used. PMID- 1433229 TI - Ring chromosome 13: lack of distinct syndromes based on different breakpoints on 13q. AB - A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation with the probe L1.26 confirmed the derivation from chromosome 13 and DNA polymorphism analysis showed maternal origin of the ring chromosome. Our results, together with a review of previous reports of cases with ring chromosome 13 with identified breakpoints, could neither support the theory of distinct clinical syndromes based on different breakpoints on 13q nor correlate the severity of symptoms with instability of the ring. PMID- 1433230 TI - Extravillus dividing fetal cells at CVS: evidence of their erythroblastic origin. AB - Cytological and cytogenetic studies were performed on nucleated fetal cells present in chorionic villus transport medium. The erythroblastic origin of these cells was shown. Fetal erythroblasts in spontaneous mitosis were frequently observed; chromosome counts were obtained from them but poor quality often prevented banded analysis. Cytogenetic study of erythroblast metaphases can be useful as an additional diagnostic aid in cases of mosaicism with aneuploid cell lines. PMID- 1433232 TI - Recognition of thalidomide defects. PMID- 1433231 TI - The gene for hereditary multiple exostoses does not map to the Langer-Giedion region (8q23-q24). AB - Hereditary multiple exostoses is a dominantly inherited skeletal disorder which alters enchondral bone during growth and is characterised by exostoses of the juxta-epiphyseal regions. Using polymorphic DNA probes, we have been able to exclude the disease gene from close proximity to the 8q24.1 region where a dominant syndrome with multiple exostoses, the trichorhinophalangeal syndrome type II (TRP II, Langer-Giedion syndrome, MIM 15025), has been previously localised (pairwise linkage Z = -8.96 at theta = 0 with probe L48 at locus D8S51). Multipoint linkage analysis using probes L48, L24, and L1 consistently excluded the HME gene from a large area of the distal long arm of chromosome 8, spanning the smallest region of overlap assigned to the TRP II gene. These studies support the clinical view that HME and TRP II are distinct entities. PMID- 1433233 TI - Postgraduate teaching in clinical genetics in the United Kingdom. PMID- 1433234 TI - The OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects): recurrence in sibs. AB - The OEIS complex comprises a combination of defects including omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects. It may represent the most severe manifestation of a spectrum of birth defects, the exstrophy epispadias sequence. The OEIS complex affects 1 in 200,000 to 400,000 pregnancies and is of unknown cause. The purpose of the current report is to document the occurrence of OEIS in sibs from separate pregnancies and suggest that some cases may have a genetic basis. PMID- 1433235 TI - Lethal olivopontoneocerebellar hypoplasia with dysmorphic features in sibs. AB - This report describes the clinical and neuropathological features in male and female sibs who died shortly after birth as a result of frequent convulsions and lack of spontaneous respiratory effect. Both sibs had a prominent occiput with mild contractures and the female also had overlapping fingers and rockerbottom feet. The genetic and neuropathological findings were consistent with a diagnosis of an autosomal recessive form of olivopontoneocerebellar hypoplasia/atrophy. PMID- 1433236 TI - A new X linked syndrome with mental retardation and craniofacial dysmorphism? AB - We present a syndrome manifested in two half brothers and their two maternal aunts which is characterised in the two boys by severe mental retardation and craniofacial dysmorphism (broad, coarse features and marked plagiocephaly with flattened occiput), and in the aunts merely by moderate mental retardation without dysmorphic features. The brothers do not seem to fall into any previously described X linked syndrome with mental retardation. PMID- 1433237 TI - Partial trisomy for 5q and monosomy for 12p in a liveborn child as a result of a complex five breakpoint chromosome rearrangement in a parent. AB - A balanced complex chromosome rearrangement (CCR) involving four chromosomes is very rare and may lead to different types of aneuploid germ cells. We report a liveborn child with multiple congenital anomalies and an apparently balanced translocation, t(11;12). High resolution chromosome analysis in the mother showed a CCR involving chromosomes 5, 11, 12, and 16. In situ hybridisation showed that this CCR was the result of a five break rearrangement, and that the derivative chromosome 12 consisted of parts of chromosomes 5, 11, and 12. From this it could be deduced that the karyotype of the child was not balanced, but resulted in partial trisomy for 5q and partial monosomy for 12p. The clinical findings in the child were compatible with partial trisomy for 5q. PMID- 1433238 TI - A male with trisomy 9 mosaicism and maternal uniparental disomy for chromosome 9 in the euploid cell line. AB - We describe a 17 year old male with a low level of trisomy 9 mosaicism. Maternal uniparental chromosome 9 disomy in the euploid cell line was shown to have arisen after postzygotic loss of the paternal chromosome 9 from the trisomic cell line by cytogenetic and molecular analysis. This is believed to be the first report of uniparental disomy for chromosome 9. In four of the 11 reported cases of mosaic trisomy 9 syndrome, including our patient, a maternally derived pericentric inversion of the heterochromatic area of chromosome 9 has been present in duplicate in the trisomic cell line. This may have implications for the counselling of patients with this common chromosomal variant. PMID- 1433239 TI - Trisomy 15 mosaicism in an IVF fetus. AB - Prenatal diagnosis of an IVF pregnancy in a woman aged 41 years showed a fetus mosaic for trisomy 15. The fetus had dysmorphic features, hypoplastic adrenal glands, and an accessory spleen. Both IVF and advanced maternal age would seem to increase the risk of trisomy 15. PMID- 1433240 TI - De novo t(X;21)(q28;q11) in a girl with phenotypic features of Williams-Beuren syndrome. AB - We describe a female infant with mental retardation and some of the phenotypic features of Williams-Beuren syndrome. Chromosome analysis showed t(X;21)(q28;q11). Diagnosis, inactivation of the X chromosome, and possible involvement of the translocation breakpoints in the pathogenesis of this syndrome are discussed. PMID- 1433241 TI - Premature chromosome condensation in a child with trisomy 21. PMID- 1433242 TI - Familial postaxial acrofacial dysostosis syndrome. PMID- 1433243 TI - Linkage disequilibrium between D16S94 and the locus for adult polycystic kidney disease (PKD1) PMID- 1433244 TI - Patent ductus arteriosus in four generations of a family. PMID- 1433245 TI - Computer modelling of brain cortex excitation by magnetic field pulses. AB - In spite of many clinical and experimental applications, the technique of transcranial magnetic stimulation still presents obscure aspects. This especially concerns safety parameters and the exact characterization of the current induced by a single magnetic pulse. The model proposed consists of an equivalent electric network derived by Maxwell's equations and applied to discretized magnetic resonance imaging of a normal subject. This model allows accurate prediction of current distribution, charge per phase and dissipated energy. PMID- 1433246 TI - Cardiac cycle phase uncertainty: another source of error in indirect blood pressure measurement. AB - Cardiac cycle phase uncertainty causes a small error in indirect estimation of arterial blood pressure by sphygmomanometry. A simple analysis yields a statistical description of the error and a rule for its reduction: correct bias by adding to the systolic estimate and subtracting from the diastolic estimate one-half of the per-cardiac-cycle cuff deflation decrement. If several measurements are taken, the least-square estimate is approximately the arithmetic mean of the greatest and least of the bias corrected estimates. PMID- 1433247 TI - Oxford Optronix MPM 3S: a clinical assessment of a microvascular perfusion monitor. AB - The Oxford Optronix MPM 3S is a new microvascular perfusion monitor which is promoted as a device for use in the operating theatre. It uses a semiconductor laser diode and applies the Doppler principle to derive a semi-quantitative estimation of microvascular flow. We assessed this instrument with eight healthy volunteers who each performed eight different orthostatic arm manoeuvres while forearm skin blood flow was monitored. The different manoeuvres caused statistically significant changes in the instrument's reading which generally were consistent with expected changes in blood flow. The monitor also was assessed in the theatre environment with four anaesthetized patients. It proved easy to use, and was not subject to electrical interference from other equipment including short-wave diathermy. The major practical limitation of the technique is the semi-quantitative nature of the measurement. The instrument appears to have potential clinical uses in plastic and vascular surgery. PMID- 1433248 TI - A proposed new paracentesis electrode for the measurement of foetal auditory brain stem response: a preliminary report. AB - A proposed new electrode for measurement of foetal auditory brain stem response (ABR) is presented, the structure of which resembles a syringe needle. It can be placed subdermally in the head of the guinea pig foetus through the wall of the maternal abdomen. In the anterior end of the electrode a special device similar to a hook is situated. The device may be controlled from outside the maternal abdomen. In comparison with the placement of electrodes through the surgical incision, its placement is simple and injury to tissue is relatively small. It is not only firmly fixed in the subcutaneous tissue of the foetus to satisfy the need for the measurement of foetal ABR, but is easily removed from the foetus. To our knowledge no other similar electrode has been reported. PMID- 1433249 TI - Rehabilitation engineering and leprosy in Nepal: a personal view. AB - Green Pastures Hospital is a specialist leprosy hospital in Pokhara, Nepal. As part of its service it offers a range of appliances aimed to assist in the rehabilitation of patients. This paper outlines the different orthoses and prostheses made at the Orthopaedic Appliances Centre in the hospital, their various indications and some of the benefits and problems associated with their use. Specific reference is made to the requirements related to local conditions and customs. The terrain, communications, facilities and materials available in Nepal make the work of the few rehabilitation engineers in the country somewhat different from that of those in the West. Some of these differences are described, drawing out contrasts in technical requirements of appliances and in organizational structures in the field of rehabilitation in the UK and Nepal. PMID- 1433250 TI - Prospects for expanding the use of beta-lactamase inhibitors. PMID- 1433251 TI - Sharing of virulence-associated properties at the phenotypic and genetic levels between enteropathogenic Escherichia coli and Hafnia alvei. AB - Seven strains of Hafnia alvei isolated from diarrhoeal stools of children resembled enteropathogenic Escherichia coli (EPEC) in that they produced attaching-effacing (AE) lesions in rabbit ileal loops and fluorescent actin staining in infected HEp-2 cells. In addition, a DNA probe from a chromosomal gene required by EPEC to produce AE lesions, hybridised to chromosomal DNA from all seven H. alvei strains. These findings indicate that there is a sharing of virulence-associated properties at the phenotypic and genetic levels by H. alvei and EPEC. H. alvei strains with these properties should be considered diarrhoeagenic. PMID- 1433252 TI - A 15-year study of the role of Aeromonas spp. in gastroenteritis in hospitalised children. AB - During a 15-year period, 146 strains of Aeromonas spp. were isolated from 32810 faecal specimens from 13,820 hospitalised patients up to 13 years of age. These isolates constituted 4% of all the pathogenic bacterial strains cultured. For the years 1978-1988, the files of children with gastro-enteritis revealed 81 whose faeces yielded Aeromonas spp. Most of them (94%) were < 3 years of age, 78% < 1 year old. The peak incidence was at 2-6 months, involving severe morbidity including dehydration and vomiting with acidaemia and azotaemia; the mean duration of illness and length of hospitalisation at this age were longer than at other ages. Bloody diarrhoea was found in 7% of the children. Almost all the strains of Aeromonas were resistant to ampicillin. We conclude that Aeromonas spp. are of aetiological significance in gastro-enteritis in small children; culture for this pathogen should be routine in the bacteriological examination of faeces. PMID- 1433253 TI - Differentiated Caco-2 cells as a model for enteric invasion by Campylobacter jejuni and C. coli. AB - A collection of 44 Campylobacter isolates (37 C. jejuni and seven C. coli) from children with colitis (21 strains) or watery diarrhoea (23 strains) was analysed for toxin production, association with HeLa cells, and invasion of differentiated Caco-2 cell cultures. There was no obvious association of clinical symptoms with species, biotype or enterotoxin production. All colitis strains and most of the isolates from watery diarrhoea were cytotoxic for Chinese hamster ovary cells. Measurements of bacterial association indices with HeLa cells varied with time, and were considered to be unreliable for discriminating between isolates from the two diagnostic groups. Statistically significant differences were observed between the two groups (all colitis strains and 65% of strains from non inflammatory diarrhoea) with respect to invasion of both HeLa and Caco-2 cell monolayers. However, among the strains from non-inflammatory diarrhoea that did invade, numbers of internalised bacteria were similar to the range observed for colitis strains. Of the colitis strains, 86% were able to transcytose through polarised Caco-2 monolayers grown on filters, compared with 48% of isolates from non-inflammatory disease. We propose the use of Caco-2 cells as a model for studying invasion of intestinal epithelia by C. jejuni and C. coli. PMID- 1433254 TI - Mononuclear cell response in the liver of mice infected with hepatotoxigenic Campylobacter jejuni. AB - Intragastric inoculation with hepatotoxigenic strains of Campylobacter jejuni led to the death of mice during the late phase of infection. Histological study disclosed a massive infiltration of mononuclear cells in the liver, mimicking intrahepatic hypersensitivity. Neither enterotoxigenic nor enteroinvasive Escherichia coli induced such a lesion. However, the same histopathological change was induced by injecting the hepatotoxic factor of hepatotoxigenic C. jejuni intravenously on two occasions separated by 14 days. Neither a single injection of an increased dose of the hepatotoxic factor nor two injections, the second of which was heat-inactivated, induced this change. Pre-treatment with rabbit antibody to the hepatotoxic factor inhibited the development of the hepatic lesion. These results suggest that C. jejuni-induced hepatic lesions in mice may be caused, at least in part, by the active moiety of the hepatotoxic factor. The possible mechanisms by which the toxic factor induces hepatitis as a consequence of hypersensitivity are discussed in relation to Guillain-Barre syndrome and Reiter's syndrome associated with C. jejuni enteritis. PMID- 1433255 TI - A biphasic system for primary isolation of mycobacteria compared to solid medium and broth culture. AB - A biphasic culture system, the MB Check, was compared with conventional culture on Lowenstein-Jensen egg (LJ) solid medium and with Bactec broth culture for primary isolation of mycobacteria from clinical samples. A total of 104 mycobacterial isolates was detected from 985 samples examined by the three methods. The most sensitive primary isolation was with LJ culture and MB Check; these methods detected 93% and 87% of all positive cultures, respectively. MB Check allowed a somewhat more rapid detection than LJ culture. The presence of atypical mycobacteria was demonstrated most rapidly with the Bactec system. PMID- 1433256 TI - Detection of bacterial interaction with lactoferrin by an enzyme-linked ligand binding assay (ELBA). AB - An enzyme-linked ligand binding assay (ELBA) was devised to measure the interaction between bacteria and human (H) or bovine (B) lactoferrin (Lf) linked to horseradish peroxidase. Reagents were calibrated for optimum colour development with o-phenylenediamine as chromophore and organisms that were either positive or negative in a radioisotope-labelled ligand binding assay (RLBA) with 125I-Lf. Good correlation of Lf binding (r = 0.89) was found between ELBA and RLBA with 169 randomly selected strains of Escherichia coli. A semi-quantitative scoring system for ELBA, corresponding to a similar system for RLBA, was established and shown to be valid for 517 strains from seven species of bacterial pathogens. ELBA was used to measure bacterial Lf binding-saturation and displacement kinetics and shown to be comparable with RLBA. ELBA may be a suitable method for examining the binding of Lf to bacteria without the need for radioactive isotopes. PMID- 1433257 TI - Yeast-specific DNA probes and their application for the detection of Candida albicans. AB - Two DNA fragments cloned from the genome of Candida albicans ATCC 10261 may be useful in the rapid diagnosis of disseminated candidosis. One sequence (probe EOB1) was specific for C. albicans (positive hybridisation with 45 strains tested). The second sequence (probe EOB2) detected C. albicans, as well as five other pathogenic Candida spp. and Saccharomyces cerevisiae, but did not react with human or bacterial DNA. Both probes were repetitive sequences in the genome of C. albicans. Probe EOB1 was used to detect, without DNA amplification, 500 C. albicans yeast cells in 1 ml of human blood. PMID- 1433258 TI - Nosocomial infection with Clostridium difficile investigated by pyrolysis mass spectrometry. AB - Fifty-eight isolates of Clostridium difficile from two distinct outbreaks were examined for inter-strain similarity by pyrolysis mass spectrometry (PMS). The first outbreak began on a geriatric acute unit and spread to a long stay geriatric facility. PMS analysis showed that most isolates from both sites were indistinguishable. Isolates obtained in the preceding year from the long stay facility were found to be closely similar to these outbreak isolates. In the second, smaller outbreak on a female medical ward in another general hospital, PMS again showed that a single strain was probably responsible. Representative isolates from these two different outbreaks were shown to be distinct. The ability to compare rapidly large numbers of isolates of C. difficile makes PMS attractive for initial screening in suspected outbreaks, providing important information for outbreak management and allowing conventional typing methods to be concentrated on relevant isolates. PMID- 1433259 TI - Diagnosis of typhus infection with Rickettsia tsutsugamushi by polymerase chain reaction. AB - Two sets of oligonucleotide primers were used to amplify the genomic DNA of Rickettsia tsutsugamushi, the causative agent of scrub typhus (tsutsugamushi disease), by the polymerase chain reaction. Each set of primers amplified 538-bp and 109-bp products, representing part of a gene encoding a possible major 58-kDa immunogenic protein, from whole genomic DNA extracted from R. tsutsugamushi strains Karp, Kato, Gilliam, Kuroki and Kawasaki. No amplification was observed from R. sibirica, R. rickettsii, mouse and human genomic DNA. DNA amplification was observed from crude lysates of peripheral whole blood, tissue homogenates and paraffin-embedded skin biopsy sections obtained from patients with scrub typhus disease. Southern blot analysis demonstrated the specificity of the amplified DNA fragments following hybridisation with a DNA probe generated from R. tsutsugamushi strain Karp. By means of this procedure, a rapid and sensitive diagnosis of scrub typhus disease can be made during the acute stage of this infection. PMID- 1433260 TI - A formalin inactivated whole SIVmac vaccine in Ribi adjuvant protects against homologous and heterologous SIV challenge. AB - Eight monkeys were immunized at 0, 4, 9, and 18 weeks with a total of 2 mg of formalin inactivated SIVmac vaccine with Ribi adjuvant. Two weeks after the last booster four immunized monkeys and two controls were challenged with 10 MID50 of live homologous virus SIVmac, and the remaining four vaccinated animals along with two controls were challenged with the heterologous SIVsm strain. All eight vaccinated monkeys resisted the virus challenge, whereas all controls became infected. Three months after the first challenge the monkeys were rechallenged with the same virus strain, without further boosting. Two of four vaccinated monkeys were still resistant to the homologous SIV strain, and three of four monkeys were resistant to the heterologous SIVsm strain. This study demonstrates vaccine induced cross-protection between SIV strains. PMID- 1433261 TI - Are gamma delta T cells important for the elimination of virus-infected cells? AB - Rhesus monkeys (Macaca mulatta) gamma delta T cells were identified using a monoclonal antibody. The relative representation of gamma delta T lymphocytes in the peripheral blood, lymph nodes, and spleen resembles that of Homo sapiens. The analysis of function and specificity revealed further significant similarities between the simian and human gamma delta T-cell systems. Since both human and monkey gamma delta T lymphocytes can effectively lyse cells infected with immunodeficiency viruses, it is possible that the primate gamma delta T-cell systems contribute to antiviral immunosurveillance. PMID- 1433262 TI - Evaluation of protective efficacy of recombinant subunit vaccines against simian immunodeficiency virus infection of macaques. AB - Simian immunodeficiency virus (SIV) was used as a model to study the protective efficacy of an immunization regimen currently being evaluated as candidate vaccines against HIV in human subjects. Four Macaca fascicularis were first immunized with recombinant vaccinia virus expressing the envelope glycoprotein gp160 of SIVmne and then boosted with subunit gp160. Both cell-mediated and humoral immune responses against SIV, including neutralizing antibodies, were elicited. The macaques were shown to be protected from a homologous virus infection as determined by serology, lymphocyte cocultivation, polymerase chain reactions and in vivo transmission analyses. Four unimmunized control animals were readily infected. However, viremia in infected control animals could decrease substantially following the initial phase of infection so that persistent infection might not be readily detectable. PMID- 1433264 TI - The impetus for tracking nonhuman primate AIDS vaccine/live virus challenge studies. PMID- 1433263 TI - Comparison of protection from homologous cell-free vs cell-associated SIV challenge afforded by inactivated whole SIV vaccines. AB - This study attempted to determine if SIV vaccines could protect against challenge with peripheral blood mononuclear cells (PBMCs) from an SIV infected rhesus monkey. Mature Macaca mulatta were vaccinated four times with formalin inactivated SIVmac32H administered in MDP adjuvant (n = 8) or SIVmac32H ISCOM vaccine (n = 8). Controls included animals vaccinated with measles virus in MDP adjuvant (n = 4) or ISCOM (n = 4) preparations. Of each group, half were challenged intravenously (IV) with ten MID50 of the cell-free SIVmac32H (11-88) SIV stock and half were challenged with ten MID50 of PBMCs from the SIVmac32H infected macaque 1XC. All SIV vaccinated animals challenged with the 11-88 cell free stock of SIVmac32H were protected, whereas only half of the SIV vaccinated monkeys receiving the same infectious dose of the 1XC cell stock were protected. PMID- 1433266 TI - Nonhuman Primate Models for AIDS IV, 9th Annual Symposium. Seattle, November 6-9, 1991. PMID- 1433265 TI - Worldwide survey of AIDS vaccine challenge studies in nonhuman primates: vaccines associated with active and passive immune protection from live virus challenge. AB - An AIDS Vaccine Surveillance System (AVSS) was designed and implemented to track the rapidly growing international database supporting the development of promising AIDS vaccines. Both preclinical nonhuman primate (NHP) and clinical human trials are tracked by the AVSS. This report presents summary data generated from the AVSS on the NHP AIDS vaccine/live virus challenge studies only. Summary data on more than 100 preclinical HIV/SIV vaccines are presented within the framework of 1) 13 arbitrary Vaccine Types, 2) studies grouped by animal model (i.e., chimpanzee/HIV-1, and macaque/SIV, HIV-2), and 3) immunization approach (i.e., active and passive). Systematic and timely presentations of these summary data, both here and in future reports, aim to promote a clearer understanding of both earlier and more recent preclinical AIDS vaccine developments. PMID- 1433267 TI - Protection against SIV infection in macaques by immunization with inactivated virus from the BK28 molecular clone, but not with BK28-derived recombinant env and gag proteins. AB - Vaccination of cynomolgus macaques with beta-propiolactone inactivated SIVmacBK28 in Freund's adjuvant induced low but detectable levels of anti-SIV envelope (env) antibodies and T-cell responses and protected against challenge with the 32H isolate of SIVmac251 grown in C8166 cells. In contrast, purified recombinant SIV env and gag proteins derived from BK28 formulated in Syntex adjuvant generated consistent and long-lived cellular and humoral immune responses to SIV env, but failed to protect against infection with the 32H virus. Thus, protection against a heterogeneous challenge stock is possible by immunization with a molecularly cloned virus, but not with recombinant proteins from the same molecular origin. High levels of anti-cell antibodies induced by the whole virus vaccine, but not by recombinant proteins, may have contributed to the protection observed. PMID- 1433268 TI - Mechanism of genital transmission of SIV: a hypothesis based on transmission studies and the location of SIV in the genital tract of chronically infected female rhesus macaques. AB - To understand the biologic processes involved in transmission of HIV, we examined the genital tracts of chronically infected female macaques and localized SIV infected cells. SIV was found in the genital tract of 12 of 16 animals and SIV infected cells were located in the cervix and vagina. Inoculation of cell-free SIV into the blind vaginal pouch of hysterectomized macaques resulted in systemic infection. We propose a hypothesis to explain the early events in the genital transmission of SIV. PMID- 1433269 TI - Simian immunodeficiency virus vectors: replication and pseudotyping. AB - We studied a single round of replication of Simian immunodeficiency virus (SIV) through the use of a replication defective vector that expresses the hygromycin resistance gene. It was possible to pseudotype SIV particles by complementation with the env gene from a murine amphotropic retrovirus. Moreover, SIV RNA was packaged and propagated by core particles of the heterologous lentivirus, HIV-1. These results indicate that coinfection of cells with SIV and other retroviruses could lead to infection of new cell types in nature. PMID- 1433270 TI - Detection of simian immunodeficiency virus DNA in macrophages from infected rhesus macaques. AB - We have examined the frequency of infection of monocyte-derived and alveolar macrophages isolated from rhesus macaques inoculated with simian immunodeficiency virus (SIVmac) utilizing a semiquantitative PCR methodology. Animals were inoculated with either pathogenic (SIVmac239) or nonpathogenic (SIVmac1A11) molecularly cloned viruses of SIVmac, or with uncloned pathogenic SIVmacBIOL. The frequency of SIV DNA in macrophages was highest early after infection and at terminal stages of disease, whereas during the asymptomatic period, SIV DNA was present at very low levels in macrophages. PMID- 1433271 TI - Characterization of group specific antibodies in primates: studies with SIV envelope in macaques. AB - Sera from SIV-infected macaques were found to contain antibodies that reacted with conformation-dependent, group-specific determinants on the SIV envelope protein gp130. These conformation-dependent antibodies exhibited virus neutralizing activity; their presence was associated with protection in vaccine studies. The properties of these antibodies are quite similar to those that have been identified in sera from HIV-infected human subjects. These data suggest that the SIV envelope gp130 remains a candidate for subunit vaccine studies. PMID- 1433272 TI - Vaccination of pregnant cynomolgus monkeys with whole formalin-inactivated SIVmac251. AB - Five pregnant (two to three and one-half months) Macaca fascicularis seroconverted following immunization with sucrose-gradient purified and formalin inactivated whole simian immunodeficiency virus (SIVmac251). No untoward effects on fetal maturation were observed during the immunization of the mothers. Antibodies to SIVmac251 (also those with in vitro neutralizing activity) were passively transferred to the offspring but disappeared within two to six months after birth. Antibodies to env glycoprotein (gp130) lasted longer than those against viral gag proteins (p26,p60). PMID- 1433273 TI - Efficacy of live-attenuated and whole-inactivated simian immunodeficiency virus vaccines against vaginal challenge with virulent SIV. AB - The ability of two vaccine preparations (UV-psoralen inactivated SIV administered intramuscularly and live-attenuated SIV inoculated intravaginally) to prevent genital transmission of virulent SIV in rhesus macaques was tested. Two of six whole-inactivated SIV vaccinated macaques, three of five live-attenuated SIV vaccinated macaques, and four of six controls became persistently infected after two separate intravaginal inoculations with a 50% animal infectious dose of virulent SIV. No association was observed between levels of SIV-specific antibodies in serum or vaginal secretions prior to challenge and subsequent infection with virulent SIV. PMID- 1433274 TI - Identification of an essential histidine residue at the active site of the tonoplast malate carrier in Catharanthus roseus cells. AB - The involvement of a histidyl residue in the binding or translocation step was investigated in the malate carrier at the tonoplast of Catharanthus roseus cells. The transport rate was strongly stimulated when the pH of the incubation medium was decreased from pH 7.0 to 5.0. The histidine-specific reagent diethylpyrocarbonate (DEPC) efficiently inhibited the activity of the malate carrier. Inhibition developed rapidly and was completed after 5 min at a concentration of 2 mM DEPC. The original substrate, malate, partially protected the carrier from inactivation by DEPC. Other organic acids (citrate, quinate) which are known to affect the malate transport of isolated vacuoles or tonoplast vesicles also showed protective properties. Inhibition of malate transport on tonoplast vesicles can also be achieved by photooxidation in the presence of the dye Rose Bengal. Malate also proved to protect against inactivation. The results strongly support the notion that a histidyl residue(s) is involved either in the binding or translocation of malate and that the protonation of the histidyl residue is essential to provide a high rate of malate transport. PMID- 1433275 TI - Effects of Ca2+ and other divalent cations on K(+)-evoked force production of slow muscle fibers from Rana esculenta and Rana pipiens. AB - Slow muscle fibers were dissected from cruralis muscles of Rana esculenta and Rana pipiens. Isometric contractures were evoked by application of K(+)-rich Ringer's containing Ca2+, Ni2+, Co2+, Mn2+ or Mg2+. High (7.2 mmol/liter) external Ca2+ concentration raised, 0 Ca2+ lowered the K+ threshold. Replacing Ca2+ by Ni2+ or Co2+ had an effect similar to that of high Ca2+ Ringer's. In Mg2+ Ringer's the K+ concentration-response curve was flattened. These effects were observed already after short exposure times in both species of slow fibers. When Ca2+ was removed for long periods of time the slow fibers of R. esculenta lost their contractile response to application of high K+ concentrations much more quickly than those of R. pipiens, while the response to caffeine (20 mmol/liter) was maintained. Upon read-mission of Ca2+ contractile ability was quickly restored in the slow fibers of both R. esculenta and R. pipiens, but the effects of Ni2+ (or Co2+, Mn2+ and Mg2+) were much larger in R. esculenta than in R. pipiens slow fibers. It is concluded that divalent cations have two different sites of action in slow muscle fibers. K+ threshold seems to be affected through binding to sites at the membrane surface; these sites bind Ni2+ and Co2+ more firmly than Ca2+. The second site is presumably the voltage sensor in the transverse tubular membrane, which controls force production, and where Ca2+ is the most effective species of the divalent cations examined. PMID- 1433276 TI - Excitation-contraction coupling in a pre-vertebrate twitch muscle: the myotomes of Branchiostoma lanceolatum. AB - The segmented trunk muscle (myotome muscle) of the lancelet (Branchiostoma lanceolatum), a pre-vertebrate chordate, was studied in order to gain information regarding the evolution of excitation-contraction (EC) coupling. Myotome membrane vesicles could be separated on isopycnic sucrose gradients into two main fractions, probably comprising solitary microsomes and diads of plasma membrane and sarcoplasmic reticulum, respectively. Both fractions bound the dihydropyridine PN 200/110 and the phenylalkylamine (-)D888 (devapamil) while specific ryanodine binding was observed in the diad preparation only. Pharmacological effects on Ca2+ currents measured under voltage-clamp conditions in single myotome fibers included a weak block by the dihydropyridine nifedipine and a shift of the voltage dependences of inactivation and restoration to more negative potentials by (-)D888. After blocking the Ca2+ current by cadmium in voltage-clamped single fibers, the contractile response persisted and a rapid intramembrane charge movement could be demonstrated. Both responses exhibited a voltage sensitivity very similar to the one of the voltage-activated Ca2+ channels. Our biochemical and electrophysiological results indicate that the EC coupling mechanism of the protochordate myotome cell is similar to that of the vertebrate skeletal muscle fiber: Intracellular Ca2+ release, presumably taking place via the ryanodine receptor complex, is under control of the cell membrane potential. The sarcolemmal Ca2+ channels might serve as voltage sensors for this process. PMID- 1433277 TI - ATP-sensitive K+ conductance in pancreatic zymogen granules: block by glyburide and activation by diazoxide. AB - The properties of transporters (or channels) for monovalent cations in the membrane of isolated pancreatic zymogen granules were characterized with an assay measuring bulk cation influx driven by a proton diffusion potential. The proton diffusion potential was generated by suspending granules in an isotonic monovalent cation/acetate solution and increasing the proton conductance of the membrane with a protonophore. Monovalent cation conductance had the sequence Rb+ > K+ > NA+ > Cs+ > LI+ > N-methyl glucamine+. The conductance could be inhibited by Ca2+, Mg2+, Ba2+, and pharmacological agents such as quinine, quinidine, glyburide and tolbutamide, but not by 5 mM tetra-ethyl ammonium or 5 mM 4 aminopyridine, when applied to the cytosolic surface of the granule membrane. Over 50% of K+ conductance could be inhibited by millimolar concentrations of ATP or MgATP. The inhibition by MgATP, but not by ATP itself, was reversed by the K+ channel opener diazoxide. The inhibitory effect is probably by a noncovalent interaction since it could be mimicked by nonhydrolyzable analogs of ATP and by ADP. The reversal of MgATP inhibition by diazoxide may be mediated by phosphorylation since it was not affected by dilution, and was blocked by the protein kinase inhibitor H7. The properties of the K+ conductance of pancreatic zymogen granule membranes are similar to those of ATP-sensitive K+ channels found in the plasma membrane of insulin-secreting islet cells, neurons, muscle, and renal cells. PMID- 1433279 TI - Elevation of cytosolic [Ca2+] due to intracellular Ca2+ release retards carbachol stimulation of divalent cation entry in rat parotid gland acinar cells. AB - This study examines the activation of divalent cation entry into rat parotid gland acinar cells by using Mn2+ as a Ca2+ surrogate cation. Following muscarinic cholinergic stimulation of dispersed parotid acini with carbachol (10 microM), the onset of internal Ca2+ release (cytosolic [Ca2+], [Ca2+]i, increase) and the stimulation of Mn2+ entry (increase in fura2 quenching) are not simultaneously detected. [Ca2+]i elevation, due to intracellular release, is detected almost immediately following carbachol addition and peak [Ca2+]i increase occurs at 6.0 +/- 0.8 sec. However, there is an interval (apparent lag) between carbachol addition and the detection of stimulated Mn2+ entry. This apparent lag is decreased from 26 +/- 3.1 sec to 9.2 +/- 1.5 sec when external Mn2+ ([Mn2+]0) is increased from 12.5 to 500 microM. It is not decreased further with increase in [Mn2+]0 from 500 microM to 1 mM (9.8 +/- 2.1 sec), although both intracellular free Mn2+ and [Mn2+-fura2]/[fura2] increase. Thus, at [Mn2+]0 < 500 microM, the observed lag time is partially due to a limitation in the magnitude of Mn2+ entry. Furthermore, neither peak [Ca2+]i nor the time required to reach peak [Ca2+]i is significantly altered by [Mn2+]0 (12.5 microM to 1 mM). At every [Mn2+]0 tested (i.e., 12.5 microM-1 mM), the apparent lag is significantly greater than the time required to reach peak [Ca2+]i. However, when carbachol stimulation of the [Ca2+]i increase is attenuated by loading the acini with the Ca2+ chelator, 2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA), there is no detectable lag in carbachol stimulation of Mn2+ entry (with 1 mM [Mn2+]0). Importantly, in BAPTA-loaded acini, carbachol stimulates Mn2+ entry via depletion of the internal Ca2+ pool and not via direct activation of other divalent cation entry mechanisms. Based on these results, we suggest that the apparent lag in the detection of carbachol stimulation of Mn2+ entry into parotid acinar cells is due to a retardation of Mn2+ entry by the initial increase in [Ca2+]i, due to internal release, which most likely occurs proximate to the site of divalent cation entry. PMID- 1433278 TI - Comparison of the properties of the ATP-sensitive K+ channels of pancreatic beta cells of lean and obese (ob/ob) C57BL/6J mice. AB - Cultures of pancreatic islet cells from obese and lean mice of the C57BL/6J strain were established and their secretory response to glucose stimulation was measured. Insulin secretion (as % of total cellular insulin content) from the cells of the obese mouse cultures was significantly higher than from lean mouse cells. The properties of the glucose- and ATP-sensitive potassium channels present in these cultured beta-cells were compared using the cell-attached and the inside-out configurations of the patch-clamp technique. The channels of both types of mouse were indistinguishable in terms of conductance, ionic selectivity, kinetic behavior, voltage dependence or sensitivity to glucose, ATP and ADP. It is concluded that the depolarized state and the hypersecretory response of obese mouse beta-cells are not related to an altered behavior of their ATP-sensitive potassium channels. PMID- 1433280 TI - Two sites for adenine-nucleotide regulation of ATP-sensitive potassium channels in mouse pancreatic beta-cells and HIT cells. AB - ATP-inhibited potassium channels (K(ATP)) were studied in excised, inside-out patches from cultured adult mouse pancreatic beta-cells and HIT cells. In the absence of ATP, ADP opened K(ATP) channels at concentrations as low as 10 microM and as high as 500 microM, with maximal activation between 10 and 100 microM ADP in mouse beta-cell membrane patches. At concentrations greater than 500 microM, ADP inhibited K(ATP) channels while 10 mM virtually abolished channel activity. HIT cell channels had a similar biphasic response to ADP except that more than 1 mM ADP was required for inhibition. The channel opening effect of ADP required magnesium while channel inhibition did not. Using creatine/creatine phosphate solutions with creatine phosphokinase to fix ATP and ADP concentrations, we found substantially different K(ATP)-channel activity with solutions having the same ATP/ADP ratio but different absolute total nucleotide levels. To account for ATP ADP competition, we propose a new model of channel-nucleotide interactions with two kinds of ADP binding sites regulating the channel. One site specifically binds MgADP and increases channel opening. The other, the previously described ATP site, binds either ATP or ADP and decreases channel opening. This model very closely fits the ADP concentration-response curve and, when incorporated into a model of beta-cell membrane potential, increasing ADP in the 10 and 100 microM range is predicted to compete very effectively with millimolar levels of ATP to hyperpolarize beta-cells. The results suggest that (i) K(ATP)-channel activity is not well predicted by the "ATP/ADP ratio," and (ii) ADP is a plausible regulator of K(ATP) channels even if its free cytoplasmic concentration is in the 10-100 microM range as suggested by biochemical studies. PMID- 1433281 TI - Subunit requirements for Torpedo AChR channel expression: a specific role for the delta-subunit in voltage-dependent gating. AB - This study examines the subunit requirement for Torpedo acetylcholine receptor (AChR) channel expression and the influence of non-alpha-subunit deletions on single AChR-channel currents. Xenopus oocytes injected with subunit combinations deficient in single non-alpha-subunit mRNA transcripts display the following order of ACh sensitivity: beta-less > gamma-less > delta-less. Oocytes injected with only the alpha-subunit and one non-alpha-subunit display the order: alpha delta > alpha gamma > alpha beta. These sequences indicate the effectiveness of non-alpha-subunit substitution is delta > gamma > beta. Single AChR-channel currents measured in oocytes deficient in either beta or gamma display conductance and voltage-sensitive burst kinetics similar to the wild-type channel. In contrast, the delta-less combination express channels with burst kinetics that are relatively faster and voltage insensitive. These results indicate that either a specific structural domain in the delta-subunit or its specific interactions with the alpha-subunit contribute to the voltage-dependent gating of the Torpedo AChR channel. PMID- 1433282 TI - Inhibition of ileal brush-border chloride conductance by specific antibody. AB - Antibody raised in mice was used in attempting to identify proteins responsible for the conductive chloride transport that can be measured in porcine ileal brush border membrane vesicles. Ileal brush-border membrane vesicle protein from pig was separated into five different molecular mass fractions by preparative SDS polyacrylamide disc gel electrophoresis. Separated protein fractions were used to immunize mice. Antibody was screened for reactivity with antigen by Western blotting, and for effects on conductive chloride transport in ileal brush border membrane vesicles. Immunization with brush-border protein from fraction I proteins (> 110 kDa) produced polyclonal antisera which specifically inhibited the conductive component of chloride uptake by ileal brush border vesicle preparations. Western blotting of the antigen showed the presence of several protein species of molecular mass > 100 kDa that were recognized by immune serum. Spleen cells from a mouse producing antiserum that inhibited conductive chloride transport were fused with a myeloma cell line. The resulting hybridoma colonies produced antibody that reacted with at least seven distinct protein bands by Western blot assay and inhibited chloride conductance in brush-border membrane vesicles. PMID- 1433283 TI - Kinetic control of 5 S RNA gene transcription. AB - We have determined that the differential transcription of somatic and oocyte-type 5 S RNA genes in a Xenopus laevis oocyte extract is a consequence of vastly different rates of stable complex assembly. Somatic-type 5 S RNA genes sequester a limiting transcription factor much more rapidly than oocyte-type 5 S RNA genes. Once formed, however, transcription complexes on both types of genes are stable, and are transcribed at nearly equivalent rates. The relative rates of stable transcription complex assembly are strongly dependent on the concentration of Mg2+. Kinetic differences in transcription complex assembly provides a key distinguishing feature between these two genes which may be used in the selective repression of oocyte-type 5 S RNA genes during the early development of Xenopus, and may also be utilized in other systems of regulated gene expression. PMID- 1433284 TI - Characterization of assembly intermediates of NADH:ubiquinone oxidoreductase (complex I) accumulated in Neurospora mitochondria by gene disruption. AB - NADH:ubiquinone oxidoreductase, the respiratory chain complex I of mitochondria, is an assembly of some 25 nuclear-encoded and 7 mitochondrially encoded subunits. The complex has an overall L-shaped structure formed by a peripheral arm and an elongated membrane arm. The peripheral arm containing one FMN and at least three iron-sulphur clusters constitutes the NADH dehydrogenase segment of the electron pathway. The membrane arm with at least one iron-sulphur cluster constitutes the ubiquinone reducing segment. We are studying the assembly of the complex in Neurospora crassa. By disrupting the gene of a nuclear-encoded subunit of the membrane arm a mutant was generated that cannot form complex I. The mutant rather pre-assembles the peripheral arm with all redox groups and the ability to catalyse NADH oxidation by artificial electron acceptors. The final assembly of the membrane arm is blocked in the mutant leading to accumulation of complementary assembly intermediates. One intermediate is associated with a protein that is not present in the fully assembled complex I. The results demonstrate that the two arms of complex I are assembled independently on separate pathways, and gave a first insight into the assembly pathway of the membrane arm. It is also shown for the first time that the obligate aerobic fungus N. crassa can grow and respire without an intact complex I. Gene replacement in this fungus is therefore a tool for investigation of this complex. PMID- 1433285 TI - Structural basis for the destabilization of F-actin by phosphate release following ATP hydrolysis. AB - The role of ATP hydrolysis in actin polymerization has been a puzzle, since it is known that polymer formation is possible without the ATPase activity and that the ATPase lags behind polymerization. We have used beryllium fluoride and G-ADP actin monomers to form F-ADP-BeF3- filaments that are a stable analog for either the ATP or the ADP-P(i) state. Electron microscopy and computed three-dimensional reconstruction have been used to compare this state to control actin, F-ADP, polymerized from G-ATP. We find, at a high degree of statistical significance, that subdomain-2 of the actin protomer in the ADP-BeF3- state is in a conformation very similar to that found in the atomic model for F-actin of Holmes and co-workers, but becomes disordered after the release of the phosphate. This breaks one of the longitudinal bonds in the filament, consistent with biochemical observations that phosphate release destabilizes F-actin. We have also found that lithium, which reduces the dissociation rate constant of actin filaments, induces a structural state indistinguishable from that of ADP-BeF3-. Further, in all states about ten C-terminal residues are displaced from the above mentioned model, but that the fit of the rest of the monomer is in excellent agreement, supporting the uniqueness of the solution they found and precluding a significantly different arrangement of the actin monomer in the filament. PMID- 1433286 TI - Inhibition of bacteriophage lambda development by the klaA gene of broad-host range plasmid RK2. AB - The kil-kor regulon of broad-host-range plasmid RK2 is an unusual array of eight co-regulated operons that express at least 21 genes, including the plasmid replication initiator gene. Some of the operons were first identified as kil loci because uncontrolled expression in the absence of certain kor regulatory genes leads to death of the host cells. The functions of kilA, C and E are unknown, although co-regulation with the replication initiator gene suggests that they may have importance in the maintenance or host range of the plasmid. Here we report studies on the function of klaA, the first of three host-lethal genes in the kilA operon. We found that lambda pklaA-1, a lambda phage containing the klaA gene, is unable to form plaques unless the host expresses the KorA and KorB repressors needed to regulate transcription from the klaA promoter. The failure to form plaques depends on the klaA gene product and results from the inability of infected cells to produce viable phage particles. Transcription of early, delayed early and late genes or processing of lambda DNA are not affected by klaA overexpression, while cell lysis, lambda DNA replication and production of functional phage heads are reduced. However, the failure to produce viable phage is best explained by the inability to synthesize lambda tails. The finding that klaA strongly inhibits a specific morphogenetic step in the assembly of lambda phage particles has significance with respect to the function of klaA on plasmid RK2. PMID- 1433287 TI - Adenovirus VARNA1 gene B block promoter element sequences required for transcription and for interaction with transcription factors. AB - We constructed mutants with a deletion of either half of the 18 base-pair B block palindrome in the VARNA1 gene, mutants with different intra-palindromic spacings, a complete set of mutants with single base substitutions, and mutants with double and triple base substitutions in the palindrome. The transcription efficiencies of these mutants were determined in human KB cell-free cytoplasmic S100 extracts. The relative competing strength of each mutant, as determined by a sequential competition experiment, was used to assess each mutant's ability to sequester factors into formation of a stable preinitiation complex. The ability of each mutant to assemble transcriptionally active preinitiation complexes was also determined by direct transcription of the isolated complexes. Finally, the ability of each mutant to interact with the transcription factor(s) TFIIIC and form a distinct gel-resolved complex was also determined. From the results of the above assays, we concluded that the two seemingly identical halves of the palindrome did not contribute equally to transcription, or to assembly of the functional preinitiation complex, nor to interaction with TFIIIC. The anterior half (B1) of the B block palindrome, which is proximal to the A block promoter element, played a stronger role in transcription and in assembly of the functional preinitiation complex than the posterior half (B2) of the palindrome. Consistent with this observation, the point mutations in four base-pairs, GTTC, from +60 to +63 in the anterior half of the B block palindrome, has the most severe effect on transcription. In contrast, we showed that the central sequence and the posterior half (B2) played a stronger role than the anterior half (B1) of the B block palindrome in the interaction of the promoter with TFIIIC. This was corroborated by the observation that base substitutions in the central four base pair sequence of the palindrome, TCGA, from +62 to +65, had the most severe effect on interaction with TFIIIC, and that mutations in most of the sequences in the posterior half of the B block palindrome had more drastic effects than mutations in the anterior half of the palindrome in this interaction. Furthermore, the spacing between the two halves of the B block palindrome had a drastic effect on the overall transcription efficiency and the interaction of the promoter with TFIIIC, suggesting that the interaction between the two halves of the B block palindrome is not only essential, but also synergistic for the interaction with TFIIIC as well as the assembly of a transcriptionally active preinitiation complex and efficient transcription. PMID- 1433288 TI - Molecular genetic analysis of bacteriophage P22 gene 3 product, a protein involved in the initiation of headful DNA packaging. AB - Bacteriophage P22 DNA packaging events occur in processive series on concatemeric phage DNA molecules. At the point where such series initiate, the DNA is recognized at a site called pac, and most molecular left ends are generated within six short regions called end sites, which are present in a 120 base-pair region surrounding the pac site. The bacteriophage P22 genes 2 and 3 proteins are required for successful generation of these ends and DNA packaging during progeny virion assembly. Mutants lacking the 162-amino-acid gene 3 protein replicate DNA and assemble functional procapsids. In this report we describe the nucleotide changes and DNA packaging phenotypes of a number of missense mutations of gene 3, which give the phage a higher than normal frequency of generalized transduction. In cells infected by these mutants, more packaging events initiate on the host chromosome than in wild-type infections, so the mutations are thought to affect the specificity of packaging initiation. In addition to having this phenotype, these mutations affect the process of phage DNA packaging in detectable ways. They may: (1) alter the target site specificity for packaging; (2) make target site recognition more promiscuous; (3) affect end site utilization; (4) alter the pac site; and (5) cause apparent random DNA packaging series initiation on phage DNA. PMID- 1433289 TI - Nuclear magnetic resonance solution structure of the alpha-neurotoxin from the black mamba (Dendroaspis polylepis polylepis). AB - The three-dimensional structure in solution of the alpha-neurotoxin from the black mamba (Dendroaspis polylepis polylepis) has been determined by nuclear magnetic resonance spectroscopy. A high quality structure for this 60-residue protein was obtained from 656 NOE distance constraints and 143 dihedral angle constraints, using the distance geometry program DIANA for the structure calculation and AMBER for restrained energy minimization. For a group of 20 conformers used to represent the solution structure, the average root-mean-square deviation value calculated for the polypeptide backbone heavy atoms relative to the mean structure was 0.45 A. The protein consists of a core region from which three finger-like loops extend outwards. It includes a short, two-stranded antiparallel beta-sheet of residues 1-5 and 13-17, a three-stranded antiparallel beta-sheet involving residues 23-31, 34-42 and 51-55, and four disulfide bridges in the core region. There is also extensive non-regular hydrogen bonding between the carboxy-terminal tail of the polypeptide chain and the rest of the core region. Comparison with the crystal structure of erabutoxin-b indicates that the structure of alpha-neurotoxin is quite similar to other neurotoxin structures, but that local structural differences are seen in regions thought to be important for binding of neurotoxins to the acetylcholine receptor. For two regions of the alpha-neurotoxin structure there is evidence for an equilibrium between multiple conformations, which might be related to conformational rearrangements upon binding to the receptor. Overall, the alpha-neurotoxin presents itself as a protein with a stable core and flexible surface areas that interact with the acetylcholine receptor in such a way that high affinity binding is achieved by conformational rearrangements of the deformable regions of the neurotoxin structure. PMID- 1433290 TI - X-ray analysis of substrate analogs in the ricin A-chain active site. AB - Ricin A-chain is an N-glycosidase that hydrolyzes the adenine ring from a specific adenosine of rRNA. Formycin monophosphate (FMP) and adenyl(3'- >5')guanosine (ApG) were bound to ricin A-chain and their structures elucidated by X-ray crystallography. The formycin ring stacks between tyrosines 80 and 123 and at least four hydrogen bonds are made to the adenine moiety. A residue invariant in this enzyme class, Arg180, appears to hydrogen bond to N-3 of the susceptible adenine. Three hypothetical models for binding a true hexanucleotide substrate, CGAGAG, are proposed. They incorporate adenine binding, shown by crystallography, but also include geometry likely to favor catalysis. For example, efforts have been made to orient the ribose ring in a way that allows solvent attack and oxycarbonium stabilization by the enzyme. The favored model is a simple perturbation of the tetraloop structure determined by nuclear magnetic resonance for similar polynucleotides. The model is attractive in that specific roles are defined for conserved protein residues. A mechanism of action is proposed. It invokes oxycarbonium ion stabilization on ribose by Glu177 in the transition state. Arg180 stabilizes anion development on the leaving adenine by protonation at N-3 and may activate a trapped water molecule that is the ultimate nucleophile in the depurination. PMID- 1433291 TI - Three-dimensional solution structure of an insulin dimer. A study of the B9(Asp) mutant of human insulin using nuclear magnetic resonance, distance geometry and restrained molecular dynamics. AB - The solution structure of the B9(Asp) mutant of human insulin has been determined by two-dimensional 1H nuclear magnetic resonance spectroscopy. Thirty structures were calculated by distance geometry from 451 interproton distance restraints based on intra-residue, sequential and long-range nuclear Overhauser enhancement data, 17 restraints on phi torsional angles obtained from 3JH alpha HN coupling constants, and the restraints from 17 hydrogen bonds, and the three disulphide bridges. The distance geometry structures were optimized using restrained molecular dynamics (RMD) and energy minimization. The average root-mean-square deviation for the best 20 RMD refined structures is 2.26 A for the backbone and 3.14 A for all atoms if the less well-defined N and C-terminal residues are excluded. The helical regions are better defined, with root-mean-square deviation values of 1.11 A for the backbone and 2.03 A for all atoms. The data analysis and the calculations show that B9(Asp) insulin, in water solution at the applied pH (1.8 to 1.9), is a well-defined dimer with no detectable difference between the two monomers. The association of the two monomers in the solution dimer is relatively loose as compared with the crystal dimer. The overall secondary and tertiary structures of the monomers in the 2Zn crystal hexamer is found to be preserved. The conformation-averaged NMR structures obtained for the monomer is close to the structure of molecule 1 in the hexamer of the 2Zn insulin crystal. However, minor, but significant deviations from this structure, as well as from the structure of monomeric insulin in solution, exist and are ascribed to the absence of the hexamer and crystal packing forces, and to the presence of monomer monomer interactions, respectively. Thus, the monomer in the solution dimer shows a conformation similar to that of the crystal monomer in molecular regions close to the monomer-monomer interface, whereas it assumes a conformation similar to that of the solution structure of monomeric insulin in other regions, suggesting that B9(Asp) insulin adopts a monomer-like conformation when this is not inconsistent with the monomer-monomer arrangement in the dimer. PMID- 1433292 TI - Domain structure and domain-domain interactions in the carboxy-terminal heparin binding region of fibronectin. AB - The domain structures and stabilities of fragments isolated from the so-called 'hep 2' region of plasma fibronectin have been investigated by differential scanning calorimetry (DSC) and fluorescence spectroscopy. The 30 kDa hep-2A fragment contains three type III modules (III12 to III14), whereas the 40 kDa hep 2B fragment contains four such modules (III12 to III15). Melting of these fragments at neutral pH was irreversible and accompanied by rapid aggregation. In contrast, melting was completely reversible in 50 mM-glycine at pH 2.7, where DSC measurements revealed the presence of three independently folded domains in 30kDa hep-2A and four in 40 kDa hep-2B. That each domain represented a single module was confirmed by measurements with four single-module subfragments, all of which melted reversibly, even at neutral pH. At neutral pH in the presence of 6 M-urea, 30 kDa hep-2A melted reversibly in a sharp peak from which only two transitions could be resolved by deconvolution. Only the larger of these was stabilized by heparin and was assigned to modules III13 and III14. Upon isolation, module III13 melted at lower temperature than in the parent fragment where it is stabilized through an interaction with module III14. We conclude that all type III modules in the hep-2 region of fibronectin constitute independently folded domains. Modules III13 and III14 form a highly co-operative structure through functionally significant interactions that can be disrupted with acid or sufficient concentrations of urea or guanidinium chloride. PMID- 1433293 TI - Structure of native and apo carbonic anhydrase II and structure of some of its anion-ligand complexes. AB - In order to obtain a better structural framework for understanding the catalytic mechanism of carbonic anhydrase, a number of inhibitor complexes of the enzyme were investigated crystallographically. The three-dimensional structure of free human carbonic anhydrase II was refined at pH 7.8 (1.54 A resolution) and at pH 6.0 (1.67 A resolution). The structure around the zinc ion was identical at both pH values. The structure of the zinc-free enzyme was virtually identical with that of the native enzyme, apart from a water molecule that had moved 0.9 A to fill the space that would be occupied by the zinc ion. The complexes with the anionic inhibitors bisulfite and formate were also studied at neutral pH. Bisulfite binds with one of its oxygen atoms, presumably protonized, to the zinc ion and replaces the zinc water. Formate, lacking a hydroxyl group, is bound with its oxygen atoms not far away from the position of the non-protonized oxygen atoms of the bisulfite complex, i.e. at hydrogen bond distance from Thr199 N and at a position between the zinc ion and the hydrophobic part of the active site. The result of these and other studies have implications for our view of the catalytic function of the enzyme, since virtually all inhibitors share some features with substrate, product or expected transition states. A reaction scheme where electrophilic activation of carbon dioxide plays an important role in the hydration reaction is presented. In the reverse direction, the protonized oxygen of the bicarbonate is forced upon the zinc ion, thereby facilitating cleavage of the carbon-oxygen bond. This is achieved by the combined action of the anionic binding site, which binds carboxyl groups, the side-chain of threonine 199, which discriminates between hydrogen bond donors and acceptors, and hydrophobic interaction between substrate and the active site cavity. The required proton transfer between the zinc water and His64 can take place through water molecules 292 and 318. PMID- 1433294 TI - Binding of the dye congo red to the amyloid protein pig insulin reveals a novel homology amongst amyloid-forming peptide sequences. AB - The three-dimensional structure has been determined of a complex of the dye Congo Red, a specific stain for amyloid deposits, bound to the amyloid protein insulin. One dye molecule intercalates between two globular insulin molecules at an interface formed by a pair of anti-parallel beta-strands. This result, together with analysis of the primary sequences of other amyloidogenic proteins and peptides suggests that this mode of dye-binding to amyloid could be general. Moreover, the structure of this dye-binding interface between protein molecules provides an insight into the polymerization of amyloidogenic proteins into amyloid fibres. Thus the detailed characterization, at a resolution of 2.5 A, of the dye binding site in insulin could form a basis for the design of agents targeted against a variety of amyloid deposits. PMID- 1433295 TI - Conformational and thermodynamic properties of supercoiled DNA. AB - We used Monte Carlo simulations to investigate the conformational and thermodynamic properties of DNA molecules with physiological levels of supercoiling. Three parameters determine the properties of DNA in this model: Kuhn statistical length, torsional rigidity and effective double-helix diameter. The chains in the simulation resemble strongly those observed by electron microscopy and have the conformation of an interwound superhelix whose axis is often branched. We compared the geometry of simulated chains with that determined experimentally by electron microscopy and by topological methods. We found a very close agreement between the Monte Carlo and experimental values for writhe, superhelix axis length and the number of superhelical turns. The computed number of superhelix branches was found to be dependent on superhelix density, DNA chain length and double-helix diameter. We investigated the thermodynamics of supercoiling and found that at low superhelix density the entropic contribution to superhelix free energy is negligible, whereas at high superhelix density, the entropic and enthalpic contributions are nearly equal. We calculated the effect of supercoiling on the spatial distribution of DNA segments. The probability that a pair of DNA sites separated along the chain contour by at least 50 nm are juxtaposed is about two orders of magnitude greater in supercoiled DNA than in relaxed DNA. This increase in the effective local concentration of DNA is not strongly dependent on the contour separation between the sites. We discuss the implications of this enhancement of site juxtaposition by supercoiling in the context of protein-DNA interactions involving multiple DNA-binding sites. PMID- 1433296 TI - Stability of a model beta-sheet in water. AB - We have used molecular dynamics simulations to determine the stability in water of a model beta-sheet formed by two alanine dipeptide molecules with two intermolecular hydrogen bonds in the closely spaced antiparallel arrangement. In this paper we describe our computations of the binding free energy of the model sheet and a portion of the free energy surface as a function of a reaction co ordinate for sheet formation. We used the free energy surface to identify stable conformations along the reaction co-ordinate. To determine whether or not the model sheet with two hydrogen bonds is more stable than a single amide hydrogen bond in water, we compared the results of the present calculations to results from our earlier study of linear hydrogen bond formation between two formamide molecules (the formamide "dimer"). The free energy surfaces for the sheet and formamide dimer each have two minima corresponding to locally stable hydrogen bonded and solvent-separated configurations. The binding free energies of the model sheet and the formamide dimer are -5.5 and -0.34 kcal/mol, respectively. Thus, the model sheet with two hydrogen bonds is quite stable while the simple amide hydrogen bond is only marginally stable. To understand the relative stabilities of the model sheet and formamide dimer in terms of solute-solute and solute-water interactions, we decomposed the free energy differences between hydrogen-bonded and solvent-separated conformations into energetic and entropic contributions. The changes in the peptide-peptide energy and the entropy are roughly twice as large for the sheet as they are for the formamide dimer. The magnitude of the peptide-water energy difference for the sheet is less than twice (by about 3.5 kcal/mol) that for the formamide dimer, and this accounts for the stability of the sheet. The presence of the side-chains and/or blocking groups apparently prevents the amide groups in the sheet from being solvated as favorably in the separated arrangement as in the formamide dimer, where the amide groups are completely exposed to the solvent. PMID- 1433297 TI - Crystallization and preliminary X-ray analysis of the complex between a mouse Fab fragment and a single IgG-binding domain from streptococcal protein G. AB - The Fab fragment of a mouse immunoglobulin G1, complexed with a single IgG binding domain from streptococcal protein G, has been crystallized in a form suitable for analysis by X-ray diffraction. The needle-shaped crystals were grown from polyethylene glycol 4000 using vapour diffusion methods and diffract to 2.3 A resolution. The space group is P2(1)2(1)2(1) (a = 64.5 A, b = 70.5 A and c = 120.1 A), with one Fab-protein G domain complex in the asymmetric unit. Solution of the three-dimensional structure of the complex will permit a detailed analysis of the molecular interactions between protein G and the Fab portion of IgG. PMID- 1433298 TI - Crystallization and preliminary X-ray investigation of bovine liver mitochondrial aldehyde dehydrogenase. AB - Aldehyde dehydrogenase from bovine liver mitochondria has been crystallized using the sitting drop method of vapor diffusion at 22 degrees C. The crystals formed from solutions containing, 40 mM-sodium citrate, 1 mM-NAD+ and 21% to 24% polyethylene glycol 3400 (pH 5.3 to 5.5). X-ray diffraction data collected from these crystals indicate that the crystals belong to the orthorhombic space group P2(1)2(1)2(1) with cell dimensions of a = 153.7 A, b = 159.37 A and c = 101.45 A. The crystals diffract to at least 2.9 A and a tetramer may comprise the asymmetric unit. PMID- 1433299 TI - Purification, crystallization and preliminary X-ray analysis of the 3 phosphoglycerate kinase from Bacillus stearothermophilus. AB - As part of a programme investigating the molecular basis of thermal stability in proteins we have isolated and characterized the thermally stable 3 phosphoglycerate kinase (PGK) from Bacillus stearothermophilus NCA 1503. The B. stearothermophilus PGK has been crystallized in a form suitable for X-ray diffraction analysis. Crystals which diffract to greater than 1.8 A resolution have been grown in the presence of the nucleotide substrate, MgATP, using polyethylene glycol (PEG 600) as a precipitant. The best crystals have been obtained using "seeding" techniques and are monoclinic, space group P2(1), with cell dimensions a = 40.5 A, b = 74.0 A, c = 68.5 A and beta = 99.8 degrees. PMID- 1433300 TI - Crystallization and initial crystallographic results for pepstatin A inhibited bovine cathepsin D. AB - Cathepsin D was purified from bovine liver by a method using two pepstatin A affinity columns. The eluted protein was combined with pepstatin A and the complex crystallized from 15% polyethylene glycol 8000 at pH 5.9. The crystals diffract to a resolution of 3.0 A and have space group P2(1)2(1)2(1) with unit cell dimensions a = 74.8 A, b = 76.0 A, c = 157.7 A. There are two molecules in the asymmetric unit. The structure was solved by molecular replacement using a pepsin search model and both molecules showed clearly interpretable density in the position expected for pepstatin A in a preliminary difference map. The refined model has r.m.s. deviations from ideal bond lengths and angles of 0.014 A and 3.2 degrees, respectively, and a crystallographic R factor of 17%. PMID- 1433301 TI - Complete nucleotide sequence and structural organization of rat cardiac troponin T gene. A single gene generates embryonic and adult isoforms via developmentally regulated alternative splicing. AB - We have previously demonstrated that rat cardiac troponin T (TnT) is expressed as two different isoforms during development, the larger, more acidic embryonic isoform and the smaller, more basic adult isoform, which appear to be generated from a common transcript of the cardiac TnT gene by alternative RNA splicing. In this study, Southern blot analysis confirmed the existence of a single copy of cardiac TnT gene in the rat genome. For investigation of the molecular mechanism of isoform switch and the control of this gene expression in myocardial development, several overlapping genomic clones were isolated from a rat genomic library. Complete nucleotide sequences were determined from these genomic clones and revealed a 19,186 base-pair DNA fragment containing 16 exons of rat cardiac TnT gene. Its DNA sequence and exon organization appeared to differ from that of the rat fast skeletal muscle TnT gene or chicken cardiac TnT gene. Comparison of genomic and cDNA clones also confirmed that the cardiac TnT isoform switching was due to the inclusion or exclusion of exon 4 during RNA processing. Sequence analysis allowed us to further identify the other alternatively spliced exon containing only nine nucleotides in size (exon 12). The inclusion and complete or partial exclusion of this exon may be responsible for generating three classes of mRNAs detected by our cDNA clones. The functional significance of this variation in TnT isoforms remained unknown, but its splicing pattern did not appear to link to the developmental changes. The 5' upstream structure was very similar to that in chicken cardiac TnT gene but differed from that in the rat fast skeletal muscle TnT gene, suggesting a similar regulatory mechanism for mammalian and avian cardiac TnT expression. PMID- 1433302 TI - Mutagenicity of a unique apurinic/apyrimidinic site in mammalian cells. AB - Abasic sites are common DNA lesions produced either spontaneously or as a consequence of the action of some genotoxic agent. The mutagenic properties of a unique abasic site replicated in mammalian cells have been studied using a shuttle vector. A plasmid, able to replicate both in mammalian cells and in bacteria, carrying a unique abasic site chemically synthesized has been constructed. After replication in mammalian cells, plasmid DNA was recovered and used to transform bacteria. Mutants were screened without selection pressure by differential hybridization with a labelled oligonucleotide and their DNA was sequenced. A mutation frequency ranging from 1% to 3% was found, depending on the base originally inserted during the vector construction, opposite the abasic site. All the sequenced mutants correspond to single base-pair substitutions targeted at the abasic site. We observed a deficit in guanine incorporation opposite the abasic site, while the three other bases were incorporated with a similar efficiency. The mutational potency of abasic sites was observed without any voluntary preconditioning treatment of mammalian cells in order to induce "SOS" like conditions. PMID- 1433303 TI - Stimulation of the phage lambda pL promoter by integration host factor requires the carboxy terminus of the alpha-subunit of RNA polymerase. AB - Escherichia coli integration host factor (IHF) binds with high affinity to two tandem IHF consensus sequences located upstream from the pL promoter of bacteriophage lambda. IHF was shown to stimulate transcription initiation from the pL promoter by increasing close complex formation (KB). We show here, by the use of reconstituted mutant RNA polymerases, that the C-terminal portion of the alpha subunit of RNA polymerase plays an essential role in the stimulation of transcription by IHF. Our results are in agreement with the hypothesis that IHF, like the cAMP-CRP activator, increases the affinity of RNA polymerase to the promoter by protein-protein interaction. PMID- 1433304 TI - Amino acid preferences of small proteins. Implications for protein stability and evolution. AB - The dependence of amino acid frequency on sequence length has been examined for the 20 natural amino acids using a set of 2275 protein sequences with little sequence identity. As expected, the frequency of cysteine increases dramatically for sequences shorter than 100 amino acids with a length-dependence that corresponds to an average of two Cys per sequence independent of length. Surprisingly dramatic changes were also observed for the frequencies of arginine, lysine, aspartic acid, and glutamic acid: Arg and Lys frequencies increase for short sequences whereas Asp and Glu frequencies decrease. These changes do not appear to be due to an over-abundance of DNA- and membrane-binding proteins in the database and may, therefore, be related to protein stability. Possible stabilizing mechanisms include increased hydrogen bonding by Arg and increased hydrophobic stabilization due to the amphiphilic character of Arg and Lys. These observations suggest that amino acid composition played an important role in the evolution of small proteins. PMID- 1433305 TI - Positive and negative effects of DNA bending on activation of transcription from a distant site. AB - Transcription of the Escherichia coli glnHPQ operon, which encodes components of the high-affinity glutamine transport system, is activated by nitrogen regulator I (NRI)-phosphate in response to nitrogen limitation. NRI-phosphate binds to sites upstream from the sigma 54-dependent glnHp2 promoter and activates transcription by catalyzing the isomerization of the closed sigma 54-RNA polymerase promoter complex to an open complex. On linear DNA, the initiation of glnHp2 transcription requires in addition to NRI-phosphate the presence of integration host factor (IHF), which binds to a site located between the NRI binding sites and the promoter. On supercoiled DNA, IHF does not play an essential role, but enhances the activation of transcription by NRI-phosphate. We found that at a mutant glnHp2 promoter with increased affinity for sigma 54-RNA polymerase, the initiation of transcription can be activated equally well by NRI phosphate in the presence or absence of IHF. Binding of IHF to its site does not increase the binding of sigma 54-RNA polymerase to the glnHp2 promoter; instead, our data suggest that IHF bends the DNA to align the activator with the closed sigma 54-RNA polymerase promoter complex to facilitate the interactions that result in open complex formation. In the absence of IHF, NRI-phosphate can activate transcription whether its binding sites are on the same face of the DNA helix as the sigma 54-RNA polymerase or on the opposite face. IHF enhances transcription when the three proteins are located on the same face of the helix, but strongly inhibits transcription when any one of the proteins is located on the opposite face. PMID- 1433306 TI - Skeletal development in Xenopus laevis (Anura: Pipidae). AB - Postembryonic skeletal development of the pipid frog Xenopus laevis is described from cleared-and-stained whole-mount specimens and sectioned material representing Nieuwkoop and Faber developmental Stages 46-65, plus postmetamorphic individuals up to 6 months old. An assessment of variation of skeletogenesis within a single population of larvae and comparison with earlier studies revealed that the timing, but not the sequence, of skeletal development in X. laevis is more variable than previously reported and poorly correlated with the development of external morphology. Examination of chondrocranial development indicates that the rostral cartilages of X. laevis are homologous with the suprarostral cartilages of non-pipoid anurans, and suggests that the peculiar chondrocranium of this taxon is derived from a more generalized pattern typical of non-pipoid frogs. Derived features of skeletal development not previously reported for X. laevis include 1) bipartite formation of the palatoquadrate; 2) precocious formation of the adult mandible; 3) origin of the angulosplenial from two centers of ossification; 4) complete erosion of the orbital cartilage during the later stages of metamorphosis; 5) development of the sphenethmoid as a membrane, rather than an endochondral bone; and 6) a pattern of timing of ossification that more closely coincides with that of the pelobatid frog Spea than that recorded for neobatrachian species. PMID- 1433307 TI - The ear in subterranean insectivora and rodentia in comparison with ground dwelling representatives. I. Sound conducting system of the middle ear. AB - Compared to acoustically unspecialized mammals (soricids and murids), the middle ear of subterranean insectivores and rodents (twelve species of six families examined) was clearly distinguished and characterized by many common features: rather round and relatively larger eardrum without a pars flaccida; reduced gonial; loose or no connection between the malleus and the tympanic bone; reduced and straightened transversal part of the malleus; enlarged incus; increased and rather flat incudo-mallear joint; rather parallel position of the mallear manubrium and incudal crus longum in some species (and their fusion in bathyergids); reduced or even missing middle ear muscles. Convergent occurrence of these structural features in taxa of different origin and their generally derived character suggest that they cannot be categorized as degenerative. The form of the stapes can be considered as a non-adaptive trait; it was taxon specific yet remarkably polymorphous in some species and exhibited no convergent features among subterranean mammals. Structural retrogression resulting in a columella-like stapes was observed in some species lacking the stapedial artery. The stapedial base was relatively larger than in unspecialized mammals. The subterranean mammals did not exhibit conspicuously enlarged eardrums as would be required for sensitive tuning to low frequencies. It is, however, argued that while selective pressures in the subterranean ecotope promoted hearing of low frequencies, hearing sensitivity did not have to be enhanced. PMID- 1433308 TI - The functional morphology of xenarthrous vertebrae in the armadillo Dasypus novemcinctus (Mammalia, Xenarthra). AB - In order to assess the mechanical properties of xenarthrous vertebrae, and to evaluate the role of xenarthrae as fossorial adaptations, in vitro bending tests were performed on posterior thoracic and lumbar vertebral segments excised from specimens of the armadillo Dasypus novemcinctus and the opossum Didelphis virginiana, the latter being used to represent the primitive mammalian condition. The columns of the two species were subjected to dorsal, ventral, and lateral bending, as well as torsion, in order to determine their stiffness in each of these directions. During these tests, bone strains in the centra of selected vertebrae were determined using rosette strain gages. Overall stiffness of the armadillo backbone at physiologically relevant displacement levels was significantly higher than that of the opossum for both dorsal and lateral bending. The two species also exhibited significant differences in angular displacement of individual vertebrae and in vertebral strain magnitudes and orientations in these two directions. No significant differences were observed when the columns of the two species were subjected to torsion or to ventral bending. Our results suggest that some, but not all, of the mechanical differences between the two species are due to the presence of xenarthrae. For example, removal of the xenarthrae from selected vertebrae (L2-L4) changes strain orientation and shear, but not strain magnitudes. Comparisons with functional data from other digging mammals indicate that the modified mechanical properties of the Dasypus column are consistent with an interpretation of xenarthrae as digging adaptations and lend support to the idea that the order Xenarthra represents an early offshoot of placental mammals specialized for fossoriality. PMID- 1433309 TI - Ultrastructural changes in guinea pig endometrial cells during the estrous cycle. AB - In the guinea pig, the estrous cycle is characterized by a constant measurable level of plasma progesterone with two peaks: the first one associated with the peak of plasma estradiol-17 beta occurring at proestrus and the second, during diestrus, more pronounced at the time at which the level of estradiol-17 beta is undetectable. The progesterone receptor content is the highest on day 1 and the lowest on day 10 of the estrous cycle, which lasts 16.3 +/- 1.5 days (n = 37; mean +/- SD). There is a positive correlation between the plasma level of estradiol-17 beta and the progesterone receptors detected immunocytochemically in both endometrial epithelial and stromal cells. The general morphology of the endometrium during proestrus and estrus is consistent with an estrogenic stimulation, i.e., a smooth and regular surface of the endometrium and the presence of numerous microvilli on the cell surface. However, a moderate secretory activity also occurs in proestrus and estrus. During postestrus, the glandular cells display an increase in characteristic secretory features which parallels the rise of progesterone in the plasma. PMID- 1433310 TI - Comparison between the effects of 2-3 butanedione monoxime (BDM) and calcium chloride on myocardial oxygen consumption. AB - The agent 2,3-butanedione monoxime (BDM) has been reported to reduce the sensitivity of myofilament force development to calcium ions, without affecting the calcium transient in myocardium. One would predict, therefore, that BDM should reduce the contractile state of the heart without reducing the amount of oxygen that is consumed to fuel the process of excitation-contraction coupling. The purpose of the present experiment was to test this hypothesis using isovolumically contracting, isolated, blood perfused canine hearts during beta blockade induced by continuous intra-coronary infusion of propranolol (1 mg/h). Contractile state was increased in seven hearts by CaCl2 infusion. Subsequently, while the CaCl2 infusion was continued at the highest rate, contractile state was reduced by BDM infusion. At each contractile state, we measured the left ventricular end-systolic pressure-volume relation (ESPVR), the relation between myocardial oxygen consumption and its mechanical correlate, pressure-volume area (MVO2 vs PVA), and the duration of the LV pressure waveform. Contractile state was quantified by interpolated developed pressure at a reference ventricular volume of 25 ml (P25). BDM infusion (0.5-7 mM) caused a dose-dependent reduction in contractile state (50% reduction in P25 at 2.4 +/- 0.3 mM), and a dose independent increase in coronary blood flow. Furthermore, BDM significantly reduced the duration of the pressure waveform up to 40% at the highest rate of BDM infusion compared to the pressure waveform duration measured at maximum CaCl2 infusion. We observed a direct relationship between MVO2 of the mechanically unloaded heart and contractility; this relation was unaffected by BDM infusion (P > 0.3). The slope of the MVO2-PVA relation decreased with increases in contractile state, but this decrease was unaffected by BDM (P > or = 0.4). We conclude that in the isolated canine heart, BDM does not act energetically as expected for a myofibrillar calcium desensitizing agent. PMID- 1433311 TI - Myoglobin supported oxygen consumption in isolated rat hearts under dysoxic conditions. AB - Oxygen consumption was assessed in contracting, isolated rat hearts subjected to Langendorff perfusion. Initially, hearts were perfused with Krebs-Henseleit bicarbonate medium (KHB). Some hearts were treated with a 10 min pulse of medium containing 0.05 mM phenylhydrazine to oxidize approximately 78% of myoglobin to a state incapable of binding oxygen. Stepwise reduction in input PO2 resulted in a decline in oxygen consumption (MO2) in control and treated hearts. Phenylhydrazine treatment had no effect upon MO2 in hearts perfused with medium having a PO2 of about 585 mmHg or higher. However, at an input PO2 of approximately 370 mmHg, MO2 was decreased to 60% of the level at an input PO2 of 710 mmHg in untreated hearts and significantly lower to 32% of initial level in myoglobin blocked hearts. In subsequent experiments, hearts were perfused with KHB containing human red blood cells (RBCs) to elevate the oxygen content of the perfusate. The addition of RBCs to medium having a PO2 of approximately 140 mmHg resulted in enhancement of MO2 and maintenance of performance. But the preparations were considered to be dysoxic since MO2 with RBCs in the medium (PO2 approximately 140 mmHg) was lower than under perfusion with KHB (PO2 approximately 710 mmHg). This should however not detract from the utility of the model in elucidating myoglobin function under oxygen limiting conditions. At an input PO2 of 140 mmHg hearts treated with phenylhydrazine to impede myoglobin function had a significantly lower MO2 and viability than untreated hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433312 TI - Effect of food restriction on the phosphocreatine energy shuttle components in rat heart. AB - Malnutrition has been associated with changes in cardiac metabolism and performance. We have previously reported a diabetic-type cardiomyopathy associated with chronic food restriction and weight loss. Because the creatine phosphocreatine-creatine kinase system is important in the contractile process, we studied the components of this system in rats fed a food-restricted diet (33% of control animal intake). After 4 weeks of food restriction, total creatine kinase (CK) activities were reduced by 28% in ventricles and by 38% in atria. The CK isoenzymes in the heart were not equally affected. The BB isoenzyme was decreased by 77% and 78%, the MB isoenzyme by 45% and 43%, the MM isoenzyme by 22% and 19% and CKmito by 16% and 15% in ventricles and atria, respectively. In contrast, brain CK activity which is predominantly the BB isoenzyme, was slightly higher in the food-restricted than in control rats. Further studies on ventricular tissue from food-restricted rats revealed a 27% decline in myofibrillar CR activity and a 58% decline in myofibrillar ATPase activity. Phosphocreatine and creatine concentrations were not changed by food restriction, however, ATP was decreased by 23% in ventricles from rats on the restricted diet. Cardiac mitochondrial oxidative phosphorylation was also impaired. State 3 respiration with alpha-ketoglutarate was reduced 20% in the food-restricted heart. These changes are compared to those which we previously observed in the diabetic rat heart and the significance of these findings is discussed. PMID- 1433313 TI - Oxidative metabolism and mechanical function in reperfused neonatal pig heart. AB - Oxidative metabolism in reperfused neonatal myocardium has not been characterized. A blood-perfused isovolumic heart preparation was used to quantify metabolic and mechanical responses of the neonatal left ventricle to global normothermic ischemia and reperfusion. Hearts from piglets aged 2-7 days were subjected to either 2 hrs of total ischemia at 37 degrees C followed by 1 hr of reperfusion or 3 hrs of perfusion alone; glucose and palmitate oxidation were measured in separate experiments by incorporation of the appropriate [14C] labeled substrate into the perfusate. In the pre-ischemic period, glucose, palmitate, and lactate contributed 10%, 41%, and 36%, respectively, to oxidative metabolism. After 2 hrs of total normothermic ischemia, oxidation of exogenous glucose was 165% and 229% of control values at 30 and 60 minutes of reperfusion, respectively; palmitate oxidation was 110% and 143% of control values at these times. Despite increased glucose oxidation, palmitate oxidation accounted for 69% of myocardial oxygen consumption after 1 hr of reperfusion, with glucose responsible for 25%. Lactate use was minimal during reperfusion. Reperfusion was accompanied by rapid and parallel recovery of oxygen utilization, mechanical function, and high-energy phosphates. The neonatal piglet heart demonstrates significant metabolic and mechanical tolerance to prolonged ischemia. Although glucose utilization increased markedly, palmitate was the primary substrate for energy production in the post-ischemic neonatal heart. PMID- 1433314 TI - Action potentials and potassium currents in rat ventricular muscle during experimental diabetes. AB - Time course of the surface electrical activity was studied in left ventricular trabeculae of Wistar rats made diabetic using streptozotocin. The action potentials were recorded in Tyrode's solution at 32 degrees C, their duration considerably increased in diabetes. By the 8th week, the prolongation was 64% at 25% of repolarization; 112% at 50% and 118% at 75%. Insulin treatment reduced the prolongation of the action potentials although a complete restoration was not achieved. 0.1 mM La3+ moderately shortened the electrical activity both in control and in diabetic trabeculae. Three mM 4-aminopyridine made the time course of control action potentials very similar to the diabetic ones while the action potentials from the diabetic animals were prolonged further to a smaller extent. Whole-cell clamp experiments in isolated ventricular myocytes (20-23 degrees C) showed a considerable decrease and a somewhat accelerated inactivation of the transient outward current (Ito) in diabetes. The steady-state inactivation and the rate of recovery from inactivation of Ito did not change. No alterations in the magnitude and voltage dependence of inward rectifier (IK1) were found around the resting membrane potential. The diabetes-related suppression of Ito explains the decreased repolarization rate of action potentials. PMID- 1433315 TI - Triacylglycerol metabolism in hypoxic, glucose-deprived rat cardiomyocytes. AB - We have recently shown that a triacylglycerol (TG)-fatty acid cycle is operating in rat myocardial cells incubated in a hypoxic, glucose-containing incubation medium (Myrmel et al., 1991a). In the present study we investigated whether this cycle occurred in hypoxic, glucose-deprived myocytes, and whether high TG levels would increase TG-fatty acid cycling and thereby energy consumption. Myocytes with elevated contents of TG were obtained from the hearts of streptozotocin induced diabetic rats (diabetic myocytes) and from normal rat myocytes prepared in the presence of oleic acid (TG-loaded myocytes). The TG content of diabetic and TG-loaded myocytes prior to hypoxic incubations was more than two times higher (P < 0.05) than that of their respective controls (123.8 +/- 20.6 and 125.3 +/- 12.7 vs 56.8 +/- 6.0 and 58.6 +/- 9.4 nmol/10(6) cells, mean +/- S.E., n = 7). Only diabetic and TG-loaded myocytes expressed marked reductions in TG content during glucose free incubations. There were no differences in TG-fatty acid cycling between the various myocyte groups, calculated as the difference between glycerol output and the concomitant decrease in TG (range: 36.7 +/- 8.1- 48.9 +/- 9.7 nmol TG/10(6) cells.2h). Apparently, the cycle was continuous throughout the whole incubation period despite falling ATP levels, contracture (rounding up) of myocytes, as well as cessation of glycogenolysis after about 40 min incubation. The cellular content of glycerol-3-phosphate, known to control TG fatty acid cycling, increased continuously and to the same extent throughout the 2 h incubation period. Futile energy consumption associated with TG-fatty acid cycling, amounted to approximately 30% of total cellular energy consumption for the whole incubation period. In conclusion, hypoxic glucose deprived rat myocytes show TG-fatty-acid cycling, even after cessation of glycogenolysis. The extent of cycling, and thus the energy cost associated with it, was not influenced by the initial level of TG in the myocytes. We propose that glycerol-3-phosphate needed to fuel the TG-fatty acid cycle after exhaustion of the glycolytic supply is derived from phospholipid degradation. PMID- 1433316 TI - The protective role of heat stress in the ischaemic and reperfused rabbit myocardium. AB - Cells subjected to increases in temperature induce the expression of several proteins known as heat shock or stress proteins. This process enhances the cell's ability to overcome the effects of further stress. In this respect, the effects of heat stress have been reported to protect the hearts of rats following ischaemia and reperfusion. We have confirmed and extended this observation, not only using different indices of myocardial injury but also in another species, namely the rabbit. Animals were anaesthetized and the body temperature raised to 42 degrees C for a 15-min period. Controls were treated in the same way but without heating. Twenty-four hours later the rabbits were re-anaesthetized and the hearts removed for either heat stress protein analysis or perfusion with Krebs buffer using an isolated perfused heart apparatus. Hearts were subjected to 60 min of low flow (1 ml/min) ischaemia followed by 30 min of reperfusion. All hearts subjected to heat stress showed an enhanced recovery of function upon reperfusion as measured by improvements in developed pressure (27.3 +/- 3.6 vs 16.3 +/- 3.0 mmHg) and diastolic pressure (37.3 +/- 7.4 vs 54.7 +/- 3.1 mmHg). In addition, creatine kinase release, associated with reperfusion, was significantly reduced in the heat-stressed hearts (532 +/- 102 vs 1138 +/- 73 mU/min/g wet wt). Myocardial accumulation and release of oxidized glutathione, an index of oxidative stress, was significantly reduced in the heat-stressed group (0.003 +/- 0.003 vs 0.376 +/- 0.113 nmol/min/g wet wt). The improved metabolic status of the reperfused heat-stressed hearts was further demonstrated by a significant conservation in the levels of ATP (6.1 +/- 0.9 vs 2.8 +/- 0.8 mumol/g dry wt) and CP (36.9 +/- 6.4 vs 16.4 +/- 5.1 mumol/g dry wt). Finally, isolated mitochondrial function in terms of respiratory control index (RCI) was maintained in the heat stressed hearts (9.2 +/- 0.9 vs 5.7 +/- 0.2) and overloading with calcium was reduced. These data extend the hypothesis that heat stress protects the heart following ischaemia and reperfusion in this in vitro model, in a way as yet undetermined. PMID- 1433317 TI - Effects of duration of ischaemia during preconditioning on mechanical function, enzyme release and energy production in the isolated working rat heart. AB - Repeated brief episodes of ischaemia "precondition" the myocardium and protect it during a subsequent period of sustained ischaemia. We subjected isolated rat hearts to sustained ischaemia with or without reperfusion after different schedules of preconditioning. We demonstrated that preconditioning with three 5 min periods of ischaemia separated by 10 min periods of reperfusion permits better functional recovery than preconditioning with three 2 min ischaemic periods separated by 10 min of reperfusion. Preconditioned hearts had creatine phosphate and adenine nucleotide levels comparable to those in the aerobically perfused controls, and showed good functional recovery. Although the mechanisms by which preconditioning protects the heart from subsequent ischaemic damage are unclear, we speculate that preservation of mitochondrial function and oxidative energy production is involved. PMID- 1433318 TI - PEG-SOD and myocardial antioxidant status during ischaemia and reperfusion: dose response studies in the isolated blood perfused rabbit heart. AB - We have previously shown that the polyethylene glycol conjugated superoxide dismutase (SOD), which has a plasma half-life of more than 24 h, protects the blood perfused rabbit heart against injury during ischaemia and reperfusion. However, the profile for the dose-dependency of protection was bell-shaped with loss of efficacy below 6000 and above 30,000 U/kg. In the present study, isolated rabbit hearts, perfused with blood from support rabbits, were subjected to a 2 min infusion with St Thomas' Hospital cardioplegic solution followed by 60 min of global ischaemia (37 degrees C) and 60 min of reperfusion. PEG-SOD was administered 1 h or 12-24 h before ischaemia. We assessed the effect of PEG-SOD on ischaemia- and reperfusion-induced changes in: (i) the tissue content of reduced glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) and (ii) the activity of CuZn-SOD, Mn-SOD and glutathione peroxidase and reductase (GPD and GRD). Ischaemia and reperfusion reduced tissue GSH content by 70% and increased GSSG content by 400% (from their fresh aerobic values of 13.1.9 and 0.09 +/- 0.01 nmol/mg protein, respectively). PEG-SOD, given intravenously at various doses to donor and support rabbits 1 h or 12-24 h before ischaemia, protected against these changes with a bell-shaped dose-response relationship. Thus, with 0, 3000, 6000, 12,000, 30,000 and 60,000 U/kg, GSH content was 4.1 +/- 0.4, 4.8 +/- 0.4, 8.5 +/- 0.5, 12.3 +/- 1.6, 12.3 +/- 1.6 and 5.0 +/- 0.5 nmol/mg protein in the 1 h pretreatment group and 4.1 +/- 0.4, 4.2 +/- 0.5, 10.4 +/- 1.5, 11.2 +/- 1.1, 11.4 +/- 0.7 and 4.7 +/- 0.6 nmol/mg protein in the 12-24 h pretreatment group (means +/- S.E.M.). For GSSG the corresponding values were 0.36 +/- 0.04, 0.34 +/- 0.03, 0.12 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.41 +/- 0.03 nmol/mg protein for the 1 h group and 0.36 +/- 0.04, 0.35 +/- 0.02, 0.15 +/- 0.01, 0.12 +/- 0.01, 0.11 +/- 0.01 and 0.34 +/- 0.02 nmol/mg protein for the 12-24 h group. Ischaemia and reperfusion had no effect on tissue MDA content or CuZn-SOD, GDP and GRD activity, and in general, PEG-SOD also lacked significant effect on any of these variables at any dose studied. However, Mn-SOD activity was severely reduced by ischaemia and reperfusion (from 42 +/- 7 U/mg protein in fresh aerobic controls to 6 +/- 1 U/mg protein at the end of reperfusion).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1433319 TI - Iron-catalyzed reactions cause lipid peroxidation in the intact heart. AB - The chemical targets and mechanisms of iron-catalyzed oxidative injury in myocardium are poorly understood. Oxygen metabolites, in the presence of iron, can initiate free-radical chain reactions in unsaturated membrane lipids, generating lipid peroxides and causing membrane injury. We examined whether exposure to iron-catalyzed oxidative injury would increase myocardial lipid peroxide levels as injury evolved in the intact heart. Isolated, buffer perfused rabbit hearts were exposed for 30 min to 100 uM Fe2+/500 uM ADP and 10 uM H2O2 (IRON group, n = 5), saline vehicle (CON group, n = 6) or 500 uM ADP and 10 uM H2O2 without iron (ADP, n = 5). Lipid peroxides were measured in cytosol and membrane fractions by a new method, using the lipid peroxide-induced oxidation of exogenous GSH to GSSG, catalyzed by the enzyme glutathione peroxidase. The results indicated that iron-catalyzed lipid peroxidation occurs in the intact heart during chemically-mediated oxidative injury. PMID- 1433320 TI - Stimulation of DNA synthesis by PDGF in the newt cardiac myocyte. AB - The adult newt cardiac ventricular myocyte has been successfully placed in cell culture and has been shown to undergo in vitro DNA synthesis. Although several growth factors have been reported to increase DNA synthesis in cardiac myocytes in vitro, PDGF has not been reported to do so, but has been shown to be active in other systems. Ventricles were removed from the adult red-spotted newt and were enzymatically and mechanically dissociated in a solution containing trypsin and collagenase. Cells were preplated on to plastic to remove non-myocytes. Myocytes were then plated onto laminin. Groups of myocytes were fed control medium and medium containing porcine PDGF. Myocytes were given 1 microCi/ml of tritiated thymidine 6 or 24 h before fixation. Control myocytes showed a peak DNA synthesis at 12-14 days in culture. One ng/ml of PDGF increased DNA synthesis significantly to 22% above control. Myocytes responded to PDGF with significantly increased DNA synthesis in about 12 h. PDGF did not induce earlier DNA synthesis, but increased synthesis at all days of culture tested. These results indicate that PDGF acts upon cardiac myocytes, increasing their DNA synthesis. PMID- 1433321 TI - Effects of sympathetic innervation on size of myocytes in embryonic rat heart cultured in oculo. AB - Embryonic rat myocardium cultured in the anterior eye chamber of an adult rat increases in mass and differentiates into mature myocardium by most morphological criteria [1]. When sympathetic innervation of grafted heart tissue was prevented by superior cervical ganglionectomy (SCGx), growth of the grafts was severely compromised. The present study used morphometric methods to examine the contribution of myocyte size to the differential growth of grafts in sympathetically denervated and intact eye chambers. For this purpose, atria or ventricles from 12-day gestation rat hearts were grafted into sympathetically denervated and intact eye chambers of male host rats. Tissue was harvested after either 2 or 8 weeks in oculo. Myocyte diameter and the ratio of cytoplasmic area to nuclear area increased between 2 and 8 weeks in oculo in both atrial and ventricular grafts. In these unloaded heart grafts, estimated myocyte size did not differ between atrial and ventricular myocytes. Grafts into sympathetically innervated and denervated eye chambers did not differ in myocyte diameter or in the ratio of cytoplasmic to nuclear area, suggesting that myocyte size cannot explain the smaller mass of grafts in sympathetically denervated eye chambers. Thus, it is likely that other factors such as myocyte proliferation, myocyte survival or altered tissue composition underlie the lesser growth of grafts not innervated by sympathetic nerves. PMID- 1433322 TI - Positive and negative inotropic effects of phorbol 12-myristate 13-acetate: relationship to PKC-dependence and changes in [Ca2+]i. AB - The present study examined the concentration-dependent effects of phorbol 12 myristate 13-acetate (PMA), a PKC-activating phorbol ester, on contractile force and [Ca2+]i in guinea-pig hearts and isolated cardiac myocytes, respectively. Contractile force was measured using isolated Langendorff-perfused hearts while [Ca2+]i was measured independently in isolated cardiac myocytes loaded with fura2 AM. Phorbol 12-myristate 13-acetate, as well as another PKC-activating phorbol, phorbol dibutyrate (PDBu), and two non-PKC-activating phorbols, alpha-phorbol didecanoate (alpha PDD) and 4 alpha-phorbol, exerted time- and concentration dependent effects on contractility. A significant positive inotropic response was observed with either PMA (10(-12) M; 5-15 min of perfusion) or PDBu (10(-12) M; 5 min of perfusion). In contrast, 10(-10) M PMA caused a significant negative inotropic effect following 30 min of perfusion while 10(-8) M PMA produced a significant negative inotropic effect which occurred earlier (10 min) and was sustained throughout the 30 min perfusion period. A similar negative inotropic effect was seen with 10(-8) M of either PDBu or alpha PDD. In addition, 4 alpha phorbol (10(-8) M) exerted a modest, but significant negative inotropic effect following 25 and 30 min of perfusion. Both concentration-dependent increases and decreases of +dF/dt and -dF/dt were observed in the presence of PMA. In addition, both PMA and PDBu caused a concentration-dependent increase in coronary perfusion pressure. The positive inotropic responses and coronary perfusion pressure effects elicited by PMA and PDBu were largely prevented by the addition of the PKC inhibitors H7 (6 nM) or HAG (10 nM); however, these drugs were without effect on the negative inotropic response to higher concentrations of both PKC activating (PMA, PDBu) and non-PKC-activating (alpha PDD, 4 alpha-phorbol) phorbol compounds. The lowest concentration of either PMA or PDBu (10(-12) M) increased the 340/380 fluorescence ratio of isolated cardiac myocytes loaded with fura2-AM on a time scale similar to that at which the positive inotropic response was seen in the whole heart. However, in contrast to results in the isolated heart, PDBu elicited a greater and sustained increase in the fluorescence ratio measured in isolated cardiac myocytes. The higher concentration of either PMA or PDBu (10(-8) M), resulted in a decrease in the 340/380 ratio.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1433323 TI - Human fetal heart development after mid-term: morphometry and ultrastructural study. AB - A total of 44 normally developed human fetal hearts aged from 17 to 40 weeks gestation were provided for routine ultrastructural and morphometric studies. For morphometric analysis, the maximal thicknesses of the anterior, lateral and posterior wall of both ventricles and that of interventricular septum were measured and the left-to-right thickness ratios calculated. The cross-sectional areas of both ventricles in the plane of the greatest heart diameter were measured with computerized image analysis system. Data were analyzed using linear regression and one-way analysis of variance. Myofibril formation occurred by attachment of thin filaments into amorphous Z materials which were presented in sarcolemmal plaques, sarcoplasmic condensations, desmosomes and in Z lines. From these Z centers, myofibrils radiated many directions and branched and anastomosed with further development. This pattern of myofibrillar development continued throughout the whole fetal period. A transverse tubule system was clearly evident in later fetal development. It occurred by invagination of sarcolemma into myocardial cells and formation of subsarcolemmal caveolae. Mitochondria, well developed Golgi complexes, glycogen granules and well-developed microvessels were found throughout the whole fetal period. Binucleated myocytes appeared by 32 weeks gestation and this suggests that myocyte hyperplasia may cease before birth in humans. The growth of both ventricular walls, the interventricular septum and that of both ventricular cross-sectional areas showed linear regression, and the left-to-right wall thickness ratios were nearly constant. Also, there were no differences in morphometric data between the left and right ventricles. In conclusion, development of the myocyte is an ongoing process which may be continued in the post-natal period in humans, and our statistical results do not support the theory of the right ventricular dominance during the fetal period. PMID- 1433324 TI - Lysophosphatidylcholine-induced Ca(2+)-overload in isolated cardiomyocytes and effect of cytoprotective drugs. AB - It has been previously demonstrated that lysophosphatides accumulate rapidly in ischaemic tissue, and may play a key role in the genesis of ischaemia-reperfusion injury. The present study investigated the effects of exogenously added lysophosphatidylcholine (1-20 microM) on single isolated cardiomyocytes from adult rabbit hearts. Quiescent cells exposed to > or = 8 microM lysophosphatidylcholine dose-dependently displayed irreversible hypercontraction, whereas after 60 min at 3 microM lysophosphatidylcholine, most cells remained rod shaped (87.2 +/- 2.0%, mean +/- S.E.M.). However, when combined with electrical field stimulation (1 Hz), exposure to 3 microM lysophosphatidylcholine resulted in irreversible hypercontracture of most cells after 60 min: only 27.5 +/- 7.5% of the cells remained rod-shaped. Contracture depended upon the presence of extracellular Ca2+, and coincided with a significant rise in the median intracellular free Ca2+ level from 72.2 to 352.1 nM (P = 0.0001), suggesting intracellular Ca(2+)-overload. Pretreatment with 10(-6) M flunarizine or R 56865 significantly reduced the fraction of damaged cells when exposed to 3 microM lysophosphatidylcholine and electrical stimulation: 78.3 +/- 12.2% and 56.3 +/- 13.1% respectively of the cells remained rod-shaped. No protection was observed when quiescent cells were exposed to 10 microM lysophosphatidylcholine. Cytochemical localization of Ca2+ showed that lysophosphatidylcholine induced a loss of sarcolemma-bound Ca2+ precipitate and an accumulation of Ca2+ clusters in mitochondria of damaged cells in a dose and time dependent way. These results suggest that lysophosphatidylcholine induces functional and structural damage (Ca(2+)-overload) in isolated cardiomyocytes and that this can be prevented by cytoprotective drugs. PMID- 1433326 TI - Female veterans seek answers: Vietnam cancer risks in question. PMID- 1433325 TI - Cardiomyocytes express albumin binding proteins. AB - We investigated whether cardiomyocytes express specific albumin binding proteins (ABP) which may function in the dissociation of fatty acids from their non covalent complexes with albumin. The experiments were performed on rat neonatal cardiomyocytes (freshly isolated and up to 3 days in culture) and on an enriched sarcolemmal fraction isolated from adult rabbit ventricular myocardium. Three types of experiments were conducted: (a) identification of ABP on electroblots of cardiomyocytes and sarcolemmal extracts reacted with [125I]-bovine serum albumin ([125I]Alb); (b) kinetic assays of [125I]Alb interaction with cardiomyocytes (at 37 degrees C), and with a sarcolemmal fraction (at 4 degrees C); (c) affinity isolation of ABP from solubilized radioiodinated sarcolemmal proteins interacted with an albumin-agarose matrix. The investigation showed that: first, two pairs of polypeptides (ABP of M(r) 18 and 31 kDa) in either cardiomyocytes or sarcolemmal fraction reacted on electroblots with [125I]Alb; second, the binding of the latter to cardiomyocytes was saturable and competed by unlabeled albumin: 50 microM albumin reduced by approximately 90% the binding of radiolabeled albumin. The sarcolemmal fraction bound [125I]Alb with a Kd of 3.66 x 10(-7) M. Thirdly, among the sarcolemmal proteins retained by the albumin-agarose matrix (18 and 31 kDa), the most prominent was the lower band (approximately 16 kDa) of the 18 kDa pair of ABP. The observations revealed that albumin interacts with relatively high affinity with specific binding sites on cardiomyocyte sarcolemma. This interaction may be a recognition step for subsequent fatty acid dissociation and translocation. PMID- 1433327 TI - Recombinant molecules may mean improved toxin therapies. PMID- 1433328 TI - RAC approves gene protocol for adult twins with AIDS. PMID- 1433329 TI - "User-friendly" cancer statistics review features new format. PMID- 1433330 TI - Primary care doctors are first defense against cancer. PMID- 1433331 TI - 102nd Congress adjourns; session included cancer issues. PMID- 1433332 TI - Meeting highlights: adjuvant therapy for primary breast cancer. PMID- 1433333 TI - Risk factors for fatal colon cancer in a large prospective study. AB - BACKGROUND: Diet, physical activity, obesity, aspirin use, and family history may all modify the risk of colon cancer, but few epidemiologic studies are large enough to examine these factors simultaneously. PURPOSE: We prospectively assessed the relationship of diet and other factors to risk of fatal colon cancer. METHODS: Using data from Cancer Prevention Study II--an ongoing prospective mortality study--we studied 764,343 adults who, in 1982, completed a questionnaire on diet and other risk factors and did not report cancer or other major illness. We assessed mortality through August 1988 and identified 1150 deaths from colon cancer (611 men and 539 women). Multivariate analyses were used to compare these case patients with 5746 matched control subjects drawn from the cohort. RESULTS: Risk of fatal colon cancer decreased with more frequent consumption of vegetables and high-fiber grains (P for trend = .031 in men and .0012 in women). The relative risk (RR) for the highest versus lowest quintile of vegetable intake was 0.76 in men (95% confidence interval [CI] = 0.57-1.02) and 0.62 in women (95% CI = 0.45-0.86). Dietary consumption of vegetables and grains and regular use of aspirin were the only factors having an independent and statistically significant association with fatal colon cancer. Participants who consumed the least vegetables and grains and no aspirin had a higher risk compared with those who consumed the most vegetables and used aspirin 16 or more times per month. For men in the former category, the RR was 2.4 (95% CI = 1.1 5.3); for women, it was 2.9 (95% CI = 1.3-6.7). Weaker associations were seen for physical inactivity, obesity, total dietary fat, and family history. No associations were seen with consumption of red meat or total or saturated fat in either sex, but this finding must be interpreted cautiously. CONCLUSIONS: These findings support recommendations that increased consumption of vegetables and grains may reduce the risk of fatal colon cancer. Regular use of low doses of aspirin may prove to be an important supplemental measure. PMID- 1433334 TI - Cancer incidence and survival among American Indians registered for Indian health service care in Montana, 1982-1987. AB - BACKGROUND: Cancer incidence and cancer survival estimates in American Indians are quite limited. PURPOSE: Our purpose was to estimate cancer incidence and survival in American Indians who were registered for Indian Health Service (IHS) care in Montana. METHODS: We linked databases from the IHS and the Montana Central Tumor Registry (MCTR) to ascertain cases for the time period from January 1, 1982, through December 31, 1987. To calculate survival rates, we used a relative survival method that incorporated age-specific risks for noncancer deaths among American Indians. RESULTS: We identified 344 cases that were compatible with the National Cancer Institute (Surveillance, Epidemiology, and End Results Program) surveillance definition of cancer. Of these cases, 249 (72%) were listed in both the MCTR and the IHS databases; 56 (16%) and 39 (11%) were listed in only the MCTR or the IHS database, respectively. Compared with the overall cancer incidence in U.S. White men, the overall cancer incidence in Montana American Indian men was markedly lower, as was the incidence for colorectal and bladder cancers and for non-Hodgkin's lymphoma. The overall cancer incidence for Montana American Indian women differed less markedly, however, from the overall incidence in U.S. White women. Compared with the cancer incidence in U.S. White women, the incidence in Montana American Indian women was significantly higher for cervical cancer but was significantly lower for colorectal, breast, and uterine cancers. Survival rates from cancer were also examined for the first time in this population. For those sites examined, the survival rates were much lower in Montana American Indians than in U.S. Whites. CONCLUSIONS: We conclude that it is feasible to develop state-specific cancer incidence and survival estimates for American Indians in at least some states in different regions of the United States. Collaboration between the IHS and a state tumor registry is likely to improve the case ascertainment achieved by either agency alone. PMID- 1433335 TI - ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients. AB - BACKGROUND: ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents. PURPOSE: Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance. METHODS: Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene. RESULTS: Patients who were clinically resistant to platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders. CONCLUSION: We conclude that ERCC1 expression levels in human tumor tissue may have a role in clinical resistance to platinum compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase. PMID- 1433336 TI - Comparative sensitivity of cells from human tumors and derivative tumor xenografts to radiation and heat treatments. AB - BACKGROUND: Human tumor xenografts in athymic mice are often used to study the efficacy of cancer treatments, but it is not known whether the xenografts accurately reflect the treatment responsiveness of the original tumors. PURPOSE: To assess the validity of tumor xenografts as specific models of neoplastic disease, a soft-agar colony assay was used to compare the sensitivity of cells from surgical tumor specimens and derivative xenograft lines to various radiation and heat treatments in vitro. METHODS: Xenograft lines were established from melanomas and from carcinomas of the bladder, breast, cervix, and colon. Single cell suspensions from the original tumors and the corresponding tumor xenografts were subjected to treatments that measured inherent radiation sensitivity, split dose radiation repair capacity, low-dose-rate radiation sensitivity, inherent heat sensitivity, capacity for development of thermotolerance, and sensitivity to step-down heating (treatment at 43.5 degrees C followed by treatment at 41.5 degrees C). Cell survival curves were plotted for each treatment, and a two tailed Student's t test was used to search for statistically significant correlations between the curves. RESULTS: Although cells from different surgical tumor specimens varied widely in their sensitivity to radiation and heat treatments, there was always a statistically significant correlation (P < .05) between the sensitivity of cells from the surgical specimens and the corresponding tumor xenografts. CONCLUSIONS: These observations strongly suggest that intrinsic properties of human tumor cells generally are retained during serial heterotransplantation. Thus, human tumor xenograft lines may be valuable tools in studies aimed at identifying cellular properties of importance for the clinical treatment sensitivity of human cancer. This does not necessarily mean, however, that the treatment responsiveness of the xenografts in vivo mirrors the clinical treatment responsiveness of the tumors in patients. PMID- 1433337 TI - DNA typing. PMID- 1433338 TI - Chemotherapy. PMID- 1433339 TI - Chemical exposure, ras oncogene activation, and acute myeloid leukemia. PMID- 1433340 TI - Chernobyl has no early effect on childhood leukemia. PMID- 1433341 TI - Old genes settle dispute over saber-tooth cat's clan. PMID- 1433342 TI - Survey says leading firms support mammography. PMID- 1433343 TI - Cancer drugs secure speedy approval in Canada. PMID- 1433344 TI - ras oncogene activation and occupational exposures in acute myeloid leukemia. AB - BACKGROUND: Epidemiologic studies of acute myeloid leukemias (AMLs) show small increases in risk of disease associated with certain occupations and chemical exposures. PURPOSE: This study was designed to determine whether the presence of mutationally activated ras oncogenes in AML are associated with occupational and chemical exposures. METHODS: We interviewed 62 patients with newly diagnosed AML (or their next-of-kin), all of whom were enrolled in a national multicenter clinical trial, and 630 healthy control subjects. DNA extracted from patients' pretreatment bone marrow samples was amplified by using the polymerase chain reaction and probed with allele-specific oligonucleotides for activating point mutations at the 12th, 13th, and 61st codons of three protooncogenes: H-ras (also known as HRAS), K-ras (also known as KRAS2), and N-ras (also known as NRAS). RESULTS: Patients with ras mutation-positive AML had a higher frequency (six of 10 patients) of working 5 or more years in an a priori high-risk occupation than did patients with ras mutation-negative AML (eight of 52; odds ratio [OR] = 6.8; 95% confidence interval [CI] = 1.3-36). Patients with ras mutation-positive AML were more likely than patients with ras mutation-negative AML to have breathed chemical vapor on the job (OR = 9.1; 95% CI = 1.3-64) or to have had skin contact with chemicals (OR = 6.9; 95% CI = 1.3-37). When ras-positive patients were compared with healthy control subjects, the ORs for occupation and occupational exposures remained elevated, while patients with ras mutation-negative AML showed no increased risk when compared with control subjects. CONCLUSION: Activation of ras proto-oncogenes may identify an etiologic subgroup of AML caused by occupation and chemical exposure. IMPLICATION: Disease etiology may be better understood if epidemiologic measures of exposure are integrated with molecular assays of the genetic defects responsible for cancer initiation and promotion. PMID- 1433345 TI - Simultaneous high-resolution measurement of adenosine triphosphate levels and blood flow in the hamster amelanotic melanoma A-Mel-3. AB - BACKGROUND: Some studies suggest that nutritional blood flow and intratumor levels of high-energy phosphates such as adenosine triphosphate (ATP) affect tumor response to treatment. Reports of intratumor variabilities have shown that distribution of high-energy phosphates within experimental and human tumors is not uniform, and this variability may be related to differences in blood flow in different regions of the tumor. However, previous studies provide no insight into the intratumor relationship of these parameters. PURPOSE: To study the intratumor relationship between blood flow and ATP concentration, we have developed a method that allows simultaneous quantitation of the two variables almost at a cellular level at adjacent sites. In addition, this technique, which uses digital image processing and analysis, facilitates regional high-resolution measurements of blood flow and ATP concentrations in relation to histology. METHODS: We examined tissue samples cut in consecutive order from one representative hamster A-Mel-3 amelanotic melanoma. Specimens from the same tumor were analyzed for histological features, blood flow (measured autoradiographically by the use of [4-N-methyl 14C]iodoantipyrine), and ATP content (measured by a quantitative substrate induced bioluminescence reaction, using single-photon imaging). The data on the three parameters were stored as digitized images, which were later transformed to reach geometric congruency. The relationship between blood flow and ATP was examined by nonlinear regression and correlation analyses. RESULTS: Regional distribution of blood flow was highly correlated with distribution of ATP within the A-Mel-3 tumor. For images of the tumor using measuring fields of approximately 20 tumor cells, the coefficient of correlation was .92 (P < .001). The relationship between the two parameters was described by a second-order function. At low blood flow values, small differences in blood flow were associated with large changes in levels of ATP, whereas at high blood flow values, differences in blood flow were associated with much smaller changes in ATP levels. CONCLUSION: This high-resolution technique may have applications in future studies investigating the relationship between tumor cell metabolism and regional blood flow and in studies aimed at identifying the locoregional target of various cancer therapies. PMID- 1433346 TI - Current serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in phenoxy acid herbicide applicators and characterization of historical levels. AB - BACKGROUND: Workers who sprayed phenoxy acid herbicides, especially those who sprayed before 1975, may have been exposed to significant amounts of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), a potent animal carcinogen present in herbicide preparations as a contaminant. PURPOSE: The aims of this study were (a) to determine serum levels of TCDD in a representative sample of workers occupationally exposed to the agent during the spraying of phenoxy acid herbicides; (b) to compare serum levels in workers exposed before 1965, when concentrations in herbicide products were unregulated and high, with levels in workers exposed after 1974, when concentrations were lower as a result of government regulations worldwide; and (c) to examine the correlation, if any, between serum levels and duration of employment in spraying. METHODS: Thirty seven subjects were randomly selected from a group of 654 men who had sprayed the herbicides 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4 dichlorophenoxyacetic acid (2,4-D) in Australia for at least 12 months. The workers were classified as follows: eight who sprayed only before 1965, nine who sprayed only during the period after 1964 and before 1975, and 20 who sprayed during the period after 1974 and before 1991. Serum from the workers was analyzed for TCDD by high-resolution gas chromatography and high-resolution mass spectrometry at a detection limit of 0.6 parts per trillion (ppt) on a lipid weight basis. In addition, rates of exposure to TCDD were estimated, as were TCDD serum concentrations at termination of employment and intensity of herbicide use. RESULTS: Only one worker, with a serum TCDD level of 34 ppt, had a serum level higher than the maximum level of 26 ppt reported for the general population. Assuming a half-life of 7.1 years, we estimated the mean exposure rates to be 2.7, 2.3, and 0.06 ppt/mo for the three epochs, respectively. We found the highest serum level of TCDD at the time of cessation of employment to be 329 ppt. Calendar period and intensity of use of 2,4,5-T and 2,4-D were statistically significant determinants of rate of exposure to TCDD, but 2,4-D was associated with exposure rate only for the pre-1975 periods. Estimated rates prior to 1965 were more than an order of magnitude higher than those after 1974. CONCLUSION: The highest estimated exposure rate was 20.7 ppt/mo, which suggests that some sprayers may have been exposed to levels comparable with those that produce cancer in laboratory animals. PMID- 1433347 TI - Effects of verapamil on the acute toxicity of doxorubicin in vivo. AB - BACKGROUND: Studies indicating that verapamil substantially enhances doxorubicin levels in certain drug-resistant tumor cells have led to the use of verapamil in combination with doxorubicin in animal and clinical studies of multidrug resistant tumors. These studies have shown this drug combination to be associated with severe toxic effects. It is important to determine whether verapamil modulates the dose-limiting and potentially lethal cardiotoxicity of doxorubicin and to elucidate possible mechanisms. PURPOSE: The aims of this study were to evaluate the in vivo effects of verapamil on (a) doxorubicin-stimulated cardiac lipid peroxidation and cardiac damage, (b) doxorubicin-induced animal mortality, and (c) biodistribution of doxorubicin to the heart. METHODS: Male (BALB/c x DBA/2)F1 mice were treated with a high dose of doxorubicin (15 mg/kg, injected intraperitoneally), verapamil (25 mg/kg, injected intraperitoneally), or combinations of the two. Lipid peroxidation was determined using the 2 thiobarbituric acid assay for malonaldehyde. Light microscopy was used for histopathologic examination of cardiac tissue. A fluorometric assay procedure was employed to determine doxorubicin levels in the heart. RESULTS: Verapamil was an effective inhibitor of peroxidative damage to myocardial lipids following a high dose of doxorubicin (15 mg/kg, injected intraperitoneally). However, mice treated with verapamil and doxorubicin had a lower survival rate and a higher initial peak concentration of doxorubicin in the heart than those treated with doxorubicin alone. They also demonstrated a higher incidence and severity of degenerative changes in cardiac tissue. CONCLUSIONS: Our findings suggest that verapamil effectively inhibits doxorubicin-mediated lipid peroxidation in vivo but that cardiac lipid peroxidation is not the major limiting mechanism underlying doxorubicin-induced toxicity. A possible explanation for the excess mortality and cardiac injury in mice treated with verapamil plus doxorubicin is that verapamil alters the pharmacokinetics of doxorubicin. IMPLICATIONS: Further studies are necessary for development of safer protocols and/or drug combinations to treat multidrug-resistant tumors. We are currently studying treatment of tumor bearing animals with a cumulative dosage regimen of doxorubicin in the presence and absence of verapamil. PMID- 1433348 TI - Re: Dietary fat and postmenopausal breast cancer. PMID- 1433349 TI - Tetrahydrobiopterin biosynthesis inhibition for diminishing nitric oxide production in cytokine-mediated septic shock. PMID- 1433350 TI - Tobacco metabolite may predict cancer risk. PMID- 1433351 TI - WHO trying to slow tobacco-related deaths in developing countries. PMID- 1433352 TI - NCI still has "designs" on food chemical research. PMID- 1433353 TI - Breast cancer prevention trial under scrutiny (again) PMID- 1433355 TI - Dermatologists warn nation of increased skin cancer risk. PMID- 1433354 TI - Problems and progress with Pap smear screening reviewed. PMID- 1433356 TI - National Cancer Institute's evaluation of unconventional cancer treatments. PMID- 1433357 TI - Pharmacokinetics of the cardioprotector ADR-529 (ICRF-187) in escalating doses combined with fixed-dose doxorubicin. AB - BACKGROUND: Although doxorubicin is an anticancer agent with a wide spectrum of activity, therapy with this anthracycline must often be discontinued at a time of benefit to the patient because of the drug's cumulative cardiotoxicity. ICRF-187 (ADR-529, dexrazoxane) is a bisdioxopiperazine compound that protects against cardiac toxicity induced by doxorubicin. PURPOSE: Our objectives in this study were to determine the maximum tolerated dose of ADR-529 (which uses a different vehicle than ICRF-187) when given with a fixed doxorubicin dose and to determine whether ADR-529 alters doxorubicin pharmacokinetics. METHODS: Twenty-five patients were treated with doxorubicin (60 mg/m2) preceded by administration of ADR-529 in escalating dosages (i.e., 60, 300, 600, 750, and 900 mg/m2) to groups of three to nine patients. ADR-529 was administered over a 15-minute period beginning 30 minutes before doxorubicin treatment; the protocol was repeated every 3 weeks. Blood was sampled frequently for drug levels, which were determined by high-pressure liquid chromatography with fluorescence (doxorubicin) and electrochemical detection (ADR-529). RESULTS: Dose-limiting neutropenia occurred in four of six previously treated patients at an ADR-529 dose of 600 mg/m2; the dose ratio of ADR-529 to doxorubicin was 10:1. For three additional patients with better Eastern Cooperative Oncology Group performance status and a maximum of one prior chemotherapy regimen, 600 mg/m2 was tolerated, but grade 3 or 4 neutropenia occurred in four of six patients who received an ADR-529 dose of 900 mg/m2 and in three of four patients at a dose of 750 mg/m2. Doxorubicin's estimated terminal half-life was 39.5 +/- 18.3 (mean +/- SD) hours; the area under the curve for plasma concentration of drug x time (AUC) was 1.74 +/- 0.40 (micrograms/microL) x hour. Total-body clearance was 598 +/- 142 microL/m2 per minute (N = 20), and it did not vary with ADR-529 dose. Estimated distribution and elimination phase half-lives for plasma ADR-529 were 0.46 +/- 0.30 hours and 4.16 +/- 2.94 hours, respectively. Total-body clearance was 111 +/- 87 microL/m2 per minute (N = 18); AUC was linear (r2 = .92), and the clearance rate was constant (r2 = .18) from 60 to 900 mg/m2. CONCLUSIONS: Myelotoxicity was dose limiting for ADR-529 at 600-750 mg/m2 when given with a fixed dose of doxorubicin at 60 mg/m2 (dose ratios of ADR-529 to doxorubicin ranged from 10:1 to 12.5:1). When used in combination, ADR-529 did not perturb doxorubicin's distribution, metabolism, or excretion; therefore, other mechanisms of cardioprotection must be involved. IMPLICATIONS: We recommend that an ADR-529 dose of 600 mg/m2 be given with single-agent doxorubicin at a dose of 60 mg/m2 in future studies. PMID- 1433359 TI - Individual variation in the activation and inactivation of metabolic pathways of cyclophosphamide. AB - BACKGROUND: Carboxyphosphamide is an inactive metabolite of cyclophosphamide, which is a widely used antineoplastic drug. Deficiencies in the production of this metabolite have been reported. Such deficiencies would have important consequences for therapeutic and toxic effects of oxazaphosphorines like cyclophosphamide. PURPOSE: This study further investigates the variability in cyclophosphamide metabolism and carboxyphosphamide recovery in urine. METHODS: The 24-hour urinary metabolic profile of cyclophosphamide was investigated in 17 Turkish patients receiving doses of 100-1080 mg orally or by short intravenous infusion. Urine samples were assayed quantitatively for cyclophosphamide and its principal metabolites (phosphoramide mustard, 4-ketocyclophosphamide, carboxyphosphamide, and dechloroethylcyclophosphamide) with combined thin-layer chromatography-photography-densitometry. The amount of each metabolite excreted in 24 hours was expressed as a percentage of the dose. RESULTS: Recovery of drug and metabolites varied greatly among individuals (range, 0.01%-13.56% of dose). In particular, the amount of carboxyphosphamide varied over a thousandfold range and was undetectable in urine from four patients. The patients were classified by phenotype as demonstrating low or high carboxylation. Those with low carboxylation excreted less than 0.2% of the cyclophosphamide dose as carboxyphosphamide, while those with high carboxylation excreted 0.8%-13.6% (median, 1.81%). No association was observed between carboxylation phenotype and patient age, sex, disease, or concomitant therapy, although the three lifetime nonsmokers all showed poor carboxylation. No correlation was observed between the percent of dose excreted as any of the other metabolites and that excreted as carboxyphosphamide. There was a statistically significant inverse correlation between the combined recovery of carboxyphosphamide and phosphoramide mustard and the dose of prednisolone administered. CONCLUSIONS: These data confirm an earlier observation of a phenotypic deficiency of carboxyphosphamide excretion in British patients treated with cyclophosphamide. This deficiency may arise from a polymorphism in the enzyme aldehyde dehydrogenase. Carboxylation phenotype may have important implications for both the therapeutic effect and toxicity of cyclophosphamide. PMID- 1433358 TI - Effects of folate deficiency and supplementation on methylnitrosourea-induced rat mammary tumors. AB - BACKGROUND: There are metabolic and epidemiologic data consistent with the hypothesis that folate deficiency increases the likelihood of cancer. Conversely, it is also known that folate is necessary for cancer growth, but few experiments in laboratory animals have evaluated the effects of folate deficiency on the development of chemically induced cancers. PURPOSE: Our purpose was to determine the effects of nutritional folate deficiency in female Fischer 344 rats on initiation and early promotion of methylnitrosourea (MNU)-induced mammary cancer. METHODS: Rats (age, 27 days) were fed a folic acid-deficient diet (AIN-76A) supplemented with glycine and succinylsulfathiazole [FA(0)]; the FA(0) diet supplemented with 2 or 40 mg of folic acid per kilogram [FA(2) or FA(40), respectively]; or the FA(0) diet supplemented with 20 mg of folinic acid per kilogram [FL(20)]. At 57 days of age, each diet-treated group (30 rats in each group) received MNU (50 mg/kg) by intravenous injection. Immediately after MNU treatment, all animals were fed the AIN-76A complete diet containing 2 mg of folic acid per kilogram. Control groups were fed the AIN-76A complete diet throughout the entire experiment. RESULTS: After 4 weeks, folate deficiency, but not anemia or growth suppression, was documented by lower folate levels in plasma and red blood cells in the group receiving the FA(0) diet. Cancer multiplicity (i.e., number of mammary cancers per number of tumor-bearing animals) at 180 days after MNU injection was 1.32, 1.90, 2.14, and 2.73 mammary cancers per tumor bearing animal in the FA(0), FA(2), FA(40), and FL(20) groups, respectively; the value in the FA(0) group was statistically significant compared with the values in the other groups. The time required for 50% of the rats to develop palpable mammary cancer was 170, 142, 100, and 85 days, respectively. The value of 170 days for the FA(0) group was statistically significant compared with the values of 100 and 85 days. Mammary cancer incidence was 63%, 70%, 72%, and 73%, respectively; these percentages were not significantly different. CONCLUSIONS: Folate deficiency suppresses and folate supplementation enhances initiation or early promotion of MNU-induced mammary cancer in rats, even when the folate deficient rats do not have anemia or growth suppression. IMPLICATION: Since the rat is relatively resistant to folate deficiency anemia, other animal models should be used to test the effect of folate nutriture on carcinogenesis. PMID- 1433360 TI - Concordance of hospital cancer registry- and physician-collected data for patients with melanoma. PMID- 1433362 TI - Unproven therapies in the treatment of cancer. PMID- 1433361 TI - T lymphocytes bearing gamma/delta-type T-cell receptor in thymic tumor tissues. PMID- 1433363 TI - The t(14;18) translocation in Hodgkin's disease. PMID- 1433364 TI - Growing number of biological therapies head toward clinical trials. PMID- 1433365 TI - Women's health research expected to remain a priority. PMID- 1433366 TI - Parents versus therapists: study seeks best coaches for children with cancer. PMID- 1433367 TI - Chromosomal abnormalities in patients with Hodgkin's disease: evidence for frequent involvement of the 14q chromosomal region but infrequent bcl-2 gene rearrangement in Reed-Sternberg cells. AB - BACKGROUND: Rearrangements of the bcl-2 gene (also known as BCL2) have been detected in up to 40% of cases of Hodgkin's disease, and it has been speculated that such rearrangements may have a role in the pathogenesis of Hodgkin's disease. PURPOSE: The purposes of this study were (a) to assess the frequency of clonal chromosomal abnormalities in Hodgkin's disease, (b) to identify recurrent changes, (c) to determine whether the bcl-2 gene rearrangement was present in Reed-Sternberg cells (the neoplastic cells of Hodgkin's disease) and their variants, and (d) to analyze whether the presence of t(14;18) translocations in Reed-Sternberg cells explains the observed bcl-2 gene rearrangements in Hodgkin's disease. METHODS: A cytogenetic study was performed on biopsy specimens from 28 consecutive untreated patients with Hodgkin's disease. The same patients were analyzed for bcl-2 gene rearrangement by a polymerase chain reaction (PCR) technique. To ascertain whether the abnormal karyotypes were present in and restricted to Reed-Sternberg cells, we also performed in situ hybridization with chromosome-specific probes. RESULTS: Abnormal metaphases were identified in 23 of the 28 patients. In 11 patients, the chromosome 14q region was abnormal; in six of these patients, there was involvement of the 14q32 region that comprises the gene encoding for heavy-chain immunoglobulin. Only one patient had a t(14;18) translocation, whereas almost 40% of these 28 patients showed bcl-2 gene rearrangements by a PCR method. The in situ hybridization method showed that the abnormal karyotype was present in and restricted to Reed-Sternberg cells. CONCLUSIONS: We conclude that the majority of cases of Hodgkin's disease contain a clonal population with an abnormal karyotype, comprising the Reed-Sternberg cells. The q32 region of chromosome 14 is frequently involved, but a t(14;18) translocation is extremely infrequent. The occurrence of a bcl-2 gene rearrangement in Hodgkin's disease most likely results from the presence of sporadic, small bystander B lymphocytes that carry the translocation and that also can be frequently detected in reactive lymphoid tissue such as tonsils. Also, a range of different chromosomal translocations may provide growth or survival advantages to Reed-Sternberg cells. PMID- 1433368 TI - Clonal origin of epithelial ovarian carcinoma: analysis by loss of heterozygosity, p53 mutation, and X-chromosome inactivation. AB - BACKGROUND: It has been suggested that multiple sites of epithelial ovarian carcinoma on the peritoneal surface reflect polyclonal disease arising from multiple primary tumors in the peritoneal mesothelium, rather than monoclonal disease spread by metastases from one primary ovarian cancer. PURPOSE: The purpose of this study was to investigate whether ovarian cancer has a monoclonal or polyclonal origin. METHODS: DNA specimens were obtained from peripheral blood lymphocytes (normal DNA) and from multiple tumor deposits of 17 women with epithelial ovarian carcinoma: primary tumors, metastatic deposits, and ascites. The clonal origin of each tumor was determined by performing (a) analysis to detect loss of heterozygosity at five loci on chromosomes 5, 11, 13, and 17; (b) sequencing of exons 5-8 of the p53 gene; and (c) X-chromosome inactivation analysis of the phosphoglycerate kinase (PGK) gene. RESULTS: In 15 of the 17 cases analyzed, there was clear evidence of monoclonal origin. The probability that the genetic events documented in these 15 cases occurred as independent events in each tumor deposit ranged from 2.5 x 10(-1) to 3.7 x 10(-16). In two cases, the pattern of allelic deletion and p53 gene mutation was compatible with either a monoclonal origin or origin from two primary ovarian tumors. CONCLUSIONS: The results did not support the hypothesis that ovarian cancer is a multifocal, polyclonal disease. Instead, the data suggest that sporadic epithelial ovarian carcinoma has either a monoclonal or a dual primary origin. IMPLICATIONS: These findings have important implications for understanding of the natural history of ovarian cancer and for clinical strategies aimed at prevention and early detection. Further studies will be required to determine the clonal origin of familial hereditary ovarian cancer. PMID- 1433369 TI - Antitumor activity and clinical pharmacology of sulofenur in ovarian cancer. AB - BACKGROUND: Sulofenur is a diarylsulfonylurea with demonstrated antitumor activity in patients with advanced epithelial ovarian cancer refractory to standard chemotherapy. The dose-limiting toxic effects observed in phase I clinical trials have been anemia and methemoglobinemia, resulting in cyanosis. PURPOSE: The purposes of this study were to further define the response rate, toxic effects, and pharmacokinetics and pharmacodynamics of sulofenur in patients with advanced ovarian cancer. METHODS: We conducted a phase II trial of sulofenur at a dose of 800 mg/m2 per day in 35 patients with stage III or IV ovarian cancer refractory to standard chemotherapy. Pharmacokinetics and pharmacodynamics were analyzed by comparing sulofenur parent and metabolite plasma levels with methemoglobin levels. RESULTS: Partial responses lasting 6.5-18 weeks occurred in four (15%; 95% confidence interval = 4%-35%) of the 26 patients assessable for response. In addition, 42% (11) of the assessable patients had prolonged stable disease (median, 20 weeks). The first nine patients received sulofenur as a daily oral dose for 14 days, with a 21-day treatment cycle. However, they developed substantial anemia and methemoglobinemia. As a result, the next 26 patients received sulofenur daily for 5 days followed by 2 days of rest for 3 consecutive weeks, with a 28-day treatment cycle (5/2-day schedule). Preclinical models predicted that 2 days of rest would decrease toxicity while maintaining antitumor activity. Patients treated with the 5/2-day schedule had relatively less severe anemia and methemoglobinemia and needed fewer red blood cell transfusions (31% versus 78% of patients), but 31% still required dose reductions because of these toxic effects. The hydroxy and keto metabolites of sulofenur had prolonged plasma half-lives relative to the parent compound, and the difference was statistically significant. In addition, the correlations of metabolite concentrations with methemoglobin levels were higher than the correlation of sulofenur concentrations with methemoglobin levels, and those differences were statistically significant. CONCLUSION: We conclude that sulofenur has modest clinical activity in heavily pretreated patients with ovarian cancer. IMPLICATIONS: The toxic effects of anemia and methemoglobinemia may limit the ultimate clinical utility of diarylsulfonylureas until less toxic derivatives with alternate metabolic pathways can be identified. PMID- 1433370 TI - Plasminogen activator and its inhibitor in cancer patients treated with tumor necrosis factor. AB - BACKGROUND: We noted the presence of plasma fibrin degradation products in patients treated with recombinant human tumor necrosis factor (TNF) in a phase I trial. PURPOSE: To further define this observation, we investigated the effects of TNF on the fibrinolytic system in patients entered in the same trial. METHODS: In the 14 patients studied, fibrinolytic parameters were measured by analyzing blood samples for tissue plasminogen activator and inhibitor at 0, 1, 2, 4, 6, and 18-24 hours after initiation of TNF treatment. We used a chromogenic substrate method to determine activity of plasminogen activator and its inhibitor and an enzyme-linked immunosorbent assay (ELISA) to determine levels of antigen (tissue-type plasminogen activator). Molecular weight was determined by zymographic assay. RESULTS: TNF treatment was associated with tissue-type plasminogen activator induction within 1 hour of TNF initiation. The plasminogen activator produced was consistent with tissue-type plasminogen activator derived from endothelium as evidenced by molecular weight analysis and ELISA. Moreover, induction of plasminogen activator inhibitor occurred following the release of tissue-type plasminogen activator, and our data suggest a dose-response effect for TNF. At high doses (i.e., 200 and 240 micrograms/m2), there was a more rapid and prolonged release of plasminogen activator inhibitor, which had an inverse relationship with the level of antigenic tissue-type plasminogen activator. Zymographic analysis showed urokinase-type plasminogen activator activity in 13 of 14 patients. In three patients, simultaneous measurements of white blood cells and tissue-type plasminogen activator revealed a temporal association between the TNF-associated rapid granulocytopenia at 30 minutes after TNF initiation and release of tissue-type plasminogen activator antigen. CONCLUSIONS: The results suggest a positive association between TNF and rapid induction of plasminogen activator activity that is consistent with an endothelial product. It is possible that, at high doses, TNF may interact directly with vascular endothelium, leading to rapid and prolonged production of plasminogen activator inhibitor. There was a dose-response effect between TNF and release of tissue-type plasminogen activator. The release of tissue-type plasminogen activator was preceded by granulocytopenia, which may indicate an association between a proposed TNF induced granulocyte-endothelial interaction in vivo and release of tissue-type plasminogen activator. IMPLICATIONS: These findings demonstrating the effects of TNF on the fibrinolytic system can be analyzed further in experimental systems to determine the implications for use of this agent as a biological response modifier in cancer therapy. PMID- 1433371 TI - Decreased catabolism of fluorouracil in peripheral blood mononuclear cells during combination therapy with fluorouracil, leucovorin, and interferon alpha-2a. AB - BACKGROUND: We previously reported that recombinant interferon alpha-2a (IFN alpha-2a) therapy was associated with a dose-dependent decrease in fluorouracil (5-FU) clearance. PURPOSE: In this study, we used peripheral blood mononuclear cells (PBMCs), which are responsive to IFNs, as surrogate tissue to determine whether the change in clearance might be explained by decrease in 5-FU catabolism during IFN alpha-2a therapy. METHODS: The study population consisted of 45 patients with adenocarcinoma arising in the gastrointestinal tract. Thirty-seven patients received therapy containing IFN alpha-2a at a median dose of 5 million U/m2 per day (range, 1.7-7.5 million U/m2 per day) starting on day 1 and continuing through either day 7 or day 14 in conjunction with intravenous high dose leucovorin (LV) followed by bolus 5-FU on days 2-6. Eight patients received the same schedule of 5-FU and LV daily for 5 days without IFN alpha-2a but with granulocyte-macrophage colony-stimulating factor starting on day 6 and ending at least 3 days prior to the start of the next cycle. Peripheral blood was collected during 70 cycles on days 1, 2, and 4 prior to the daily treatment with IFN alpha 2a + 5-FU+LV and during 19 cycles on days 1 and 4 prior to the daily treatment with 5-FU+LV without IFN alpha-2a. In a given patient cycle, matched samples were drawn at approximately the same time of day. PBMCs were isolated, and the intact cells were exposed to 4 microM [3H]5-FU, and the formation of [3H]dihydrofluorouracil was determined by reverse-phase high-performance liquid chromatography. RESULTS: In 47 matched patient cycles from IFN alpha-2a + 5-FU+LV treated patients in which samples were available on days 1, 2, and 4, 5-FU catabolism decreased by 20% (P2 = .03) and 41% (P2 = .0001) from the baseline catabolic rate (2.5 +/- 0.2 pmol/min per 10(6) cells [mean +/- SE]) on days 2 and 4, respectively. Using information from all paired samples, the mean change from baseline on day 2 was -0.4 +/- 0.2 pmol/min per 10(6) cells (n = 54; P2 = .05), and the change from baseline on day 4 was -1.3 +/- 0.3 pmol/min per 10(6) cells (n = 63; P2 = .0001). In contrast, changes in 5-FU catabolism were not evident in the PBMCs of the reference population receiving 5-FU+LV without IFN alpha-2a. CONCLUSIONS: The magnitude of the change in 5-FU catabolism is similar to the magnitude of the decrease in 5-FU clearance in our previous study. These observations suggest that changes in 5-FU catabolism during therapy with IFN alpha-2a, 5-FU, and LV may account for the decreased 5-FU clearance. PMID- 1433373 TI - Serum interleukin-6 levels in metastatic renal cell cancer: correlation with survival but not an independent prognostic indicator. PMID- 1433372 TI - Can thymidine kinase levels in breast tumors predict disease recurrence? AB - BACKGROUND: Our previous study of thymidine kinase (TK) levels in the serum of breast cancer patients demonstrated a statistically significant positive correlation with cancer stage. In postsurgical follow-up studies of 20 patients with primary breast cancer, total serum TK levels rose with disease recurrence and continued to rise with disease progression but decreased with treatment response. PURPOSE: This study was designed to examine whether TK levels in primary breast tumors can be used to predict recurrence and to establish the relationship between TK levels and estrogen receptor (ER) status and recurrence. METHODS: Eighty-six patients with breast cancer were entered in this study. Tumors were assessed for ER status and TK levels, and the patients had follow-up for recurrence over a period of 41 months. By calculating the percent of TK activity in the presence of adenosine triphosphate (ATP) or cytidine triphosphate (CTP), we estimated the relative contributions of TK isozymes TK1 and TK2 to total TK activity. RESULTS: Total TK (TK1 plus TK2) levels in tumors were significantly (P < .001) elevated in patients who subsequently had recurrence compared with levels in those who did not. Calculations of the percent of TK activity in the presence of ATP or CTP showed that this elevation was due to increased TK1 isozyme levels. ER-negative (ER-) patients had significantly (P < .001) increased TK1 levels relative to those in ER-positive (ER+) patients. ER- patients with recurrence had significantly (P < .001) elevated total tumor TK levels compared with levels in those who did not have recurrence, and calculation of percent of TK activity with ATP or CTP indicated elevated TK1 levels. A similar pattern of increased levels of total tumor TK and TK1 was observed in ER+ patients with recurrence. CONCLUSIONS: The results indicate that total tumor TK levels were significantly higher in breast cancer patients who subsequently had recurrence than levels in those who did not. This finding appears to be largely caused by higher levels of TK1. IMPLICATIONS: Higher TK1 levels in tumors in patients who subsequently had disease recurrence almost certainly indicate a high rate of proliferation in such tumors at the time of excision. It appears that TK is a potentially useful marker in the management of breast cancer. With measurement of levels of TK, particularly TK1, in breast tumors and serum, it may be possible to predict recurrence of breast cancer. PMID- 1433374 TI - Oral etoposide in treatment of advanced refractory sarcomas. PMID- 1433375 TI - Immunosuppression by chronic exposure to N-nitrosodimethylamine (NDMA) in mice. AB - Immunosuppression of humoral and cellular responses following chronic oral exposure to 1, 5, 10, and 20 ppm N-nitrosodimethylamine (NDMA) was examined in CD 1 mice. Monitoring of cumulative mortality and the incidence of peritoneal ascites in animals showed an NDMA dose-related mortality and hepatotoxicity. No visible changes in immunological parameters were noted at the 1 ppm NDMA dose. Immunosuppression of immunoglobulin M (IgM) antibody response by NDMA to sheep red blood cells (SRBC) was time-related, dose-related, and could be reversed within 30 d by removal of the chemical from the drinking water. Cellular immune response, monitored by allogeneic stimulation of cells in mixed lymphocyte reaction (MLR), was markedly suppressed by 10 and 20 ppm NDMA. Thus, chronic exposure to NDMA, except for the low-hepatotoxic doses of nitrosamine, resulted in a marked and persistent immunosuppression of cellular and humoral responses in CD-1 mice. In conclusion, chronic exposure to the hepatotoxic (ascite-inducing) doses of NDMA suppressed humoral and cellular immunity. The persistent immunosuppression could be reversed after the removal of NDMA from the drinking water. Although no direct NDMA-related cancer was reported in humans, our data point to a potential epigenetic carcinogenicity of nitrosamines due to chronic immunosuppression. PMID- 1433376 TI - Metal levels in regrown feathers: assessment of contamination on the wintering and breeding grounds in the same individuals. AB - Birds are useful indicators of environmental contamination because they are relatively large, conspicuous, top predators in food chains. However, concentrations of contaminants in a bird's tissues reflect the bird's exposure over wide temporal and spatial scales. Birds are most useful as monitors of exposure when these scales are known. In this paper we report concentrations of lead, cadmium, mercury, and selenium in breast feathers of common terns (Sterna hirundo) and roseate terns (S. dougallii) trapped during incubation at breeding colonies in New York and Massachusetts. Terns arrived on the breeding grounds with breast feathers grown on their wintering grounds, and regrew certain feathers that were plucked for analysis. The regrown feathers were themselves plucked, and both sets of feathers were analyzed. For roseate terns at Cedar Beach and common terns at both sites there was a significant increase in mercury levels in the feathers grown on the breeding grounds compared to those grown on the wintering ground. The differences in mercury were far greater at Bird Island than at Cedar Beach. Selenium levels at Cedar Beach were higher for the regrown feathers than the initial feathers for roseate terns, but not for common terns. Lead and cadmium levels were not significantly different at either site for either species. These results suggest that terns are exposed to significantly higher levels of mercury in the northeastern United States than they are in the wintering grounds in South America. PMID- 1433377 TI - Biochemical toxicology and disposition of Therminol 66 heat transfer fluid after inhalation or after dietary administration to male Sprague-Dawley rats. AB - The objectives of this study were to determine the disposition of Therminol 66 in rats and to determine the effects of this heat-transfer fluid on liver and kidney microsomal drug-metabolizing enzymes. Therminol 66 was administered to male Sprague-Dawley rats at various doses as either a single oral administration at 0, 100, or 300 mg/kg, or as a single 6-h inhalation exposure at 0 or 350 mg/m3. Animals were killed 48 h after gavage or after termination of inhalation exposure. Additional groups of animals were exposed to Therminol 66 via the diet at 0, 100, 500, or 5000 ppm for 14 d, or via repeated inhalation exposure at 0, 25, 250, or 1200 mg/m3 for 6 h/d for 14 d. These exposure scenarios represent approximately equivalent doses of Therminol 66 by the different routes of administration. No change in body weight was observed after acute oral or inhalation exposure, and little change in body weight was observed in animals administered Therminol 66 via the diet except at the highest dose. There was no change in kidney weight, and liver weights were increased only at the higher doses of Therminol 66. The body weight gain of animals exposed to Therminol 66 via inhalation decreased in a dose-dependent manner over the 2-wk exposure period. Results from the disposition study indicated that Therminol 66 did not appear to accumulate in the tissues examined and did not appear to be extensively absorbed after a single oral dose of 300 mg/kg. The whole-body elimination half life was approximately 14 h and occurred primarily via the feces. There was no significant induction of hepatic aryl hydrocarbon hydroxylase (AHH) activity after single oral or inhalation exposures to Therminol 66. Ethoxycoumarin O deethylase (ECOD) was significantly induced only in animals exposed to 350 mg/m3 via inhalation. Repeated dietary and inhalation exposures resulted in AHH and ECOD induction only at the highest doses, and the kidney appeared to be less sensitive than the liver. Animals exposed via inhalation demonstrated a greater hepatic inductive effect than did animals exposed via the diet, which may be due to absorption differences.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1433378 TI - Contrasting respirable quartz and kaolin retention of lecithin surfactant and expression of membranolytic activity following phospholipase A2 digestion. AB - Respirable-sized quartz, a well-established fibrogenic mineral dust, is compared with kaolin in erythrocyte hemolysis assays after treatment with saline dispersion of dipalmitoyl phosphatidylcholine, a primary phospholipid component of pulmonary surfactant. Both dusts are rendered inactive after treatment, but the membranolytic activity is partly to fully restored after treatment with phospholipase A2, an enzyme normally associated with cellular plasma membranes and lysosomes. Phospholipid-coated dusts were incubated for periods of 2-72 h at a series of applied enzyme concentrations, and the adsorbed lipid species and hemolytic activity were quantitated at each time for both dusts. Surfactant was lost more readily from quartz than from kaolin, with consequent more rapid restoration of mineral surface hemolytic activity for quartz. Interactions of surfactant and mineral surface functional groups responsible for the mineral specific rate differences, and implications for determining the mineral surface bioavailability of silica and silicate dusts, are discussed. PMID- 1433379 TI - Distribution of iodine into blood components of the Sprague-Dawley rat differs with the chemical form administered. AB - It has been reported previously that radioactivity derived from iodine distributes differently in the Sprague-Dawley rat depending on the chemical form administered (Thrall and Bull, 1990). In the present communication we report the differential distribution of radioactivity derived from iodine (I2) and iodide (I ) into blood components. Twice as much radioiodine is in the form of I- in the plasma of animals treated with 125I- compared to 125I2-treated rats. No I2 could be detected in the plasma. With an increase in dose, increasing amounts of radioactivity derived from 125I2-treated animals distribute to whole blood compared to equivalent doses of 125I-, reaching a maxima at a dose of 15.8 mumol I/kg body weight. Most of the radioactivity derived from I2 associates with serum proteins and lipids, in particular with albumin and cholesteryl iodide. These data indicate a differential distribution of radioactivity depending on whether it is administered as iodide or iodine. This is inconsistent with the commonly held view that iodine (I2) is reduced to iodide (I-) before it is absorbed systemically from the gastrointestinal tract. PMID- 1433380 TI - Induction of transient airway hyperresponsiveness by exposure to 4 ppm nitrogen dioxide in guinea pigs. AB - In the present study, we investigated (1) whether airway responsiveness to inhaled histamine-aerosol could be induced during 7-d exposure of guinea pigs to 4 ppm NO2 and, if so, (2) whether thromboxane A2 may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n = 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO2 for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw0) did not change significantly after exposure to 4 ppm NO2 or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO2, the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl (SRaw after inhalation of 0.9% NaCl), were 1.07 +/- 0.20, 1.30 +/- 0.20, and 1.01 +/- 0.18 mM for the 3 groups later given NO2 for 1, 3, and 7 d, respectively. Following exposure to NO2 for 1, 3, or 7 d, EC200His values were 1.42 +/- 0.25, 0.66 +/- 0.10 (p < .05), and 1.05 +/- 0.22 mM, respectively. These results show that 7-d exposure to 4 ppm NO2 induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO2 than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long-term exposure, and (2) thromboxane A2 may play an important role in this transient airway hyperresponsiveness. PMID- 1433381 TI - Voltage-dependent potassium currents in cultured trout oligodendrocytes. AB - Ionic currents were recorded in cultured oligodendrocytes from the brain of trout using the whole-cell configuration of the patch-clamp technique. Outward currents were evoked at membrane potentials more positive than -40 mV, which could be separated into two components according to their kinetic parameters and their sensitivity to the holding potential: a fast inactivating current which was completely suppressed by 4-aminopyridine and reduced by tetraethylammonium and a slow steady-state conductance which was similarly sensitive to both potassium channel blockers. The current reversal potential was close to the potassium equilibrium potential. In contrast to mammalian oligodendrocytes but in similarity with cultured Schwann cells, trout oligodendrocytes did not exhibit any inwardly rectifying currents at hyperpolarized membrane potentials. PMID- 1433382 TI - Novel stage in the oligodendrocyte lineage defined by reactivity of progenitors with R-mAb prior to O1 anti-galactocerebroside. AB - The developmentally regulated appearance of surface immuno-reactivity of proligodendroblasts [oligodendrocyte progenitors reacting with monoclonal antibodies A007 and O4, but not anti-galactocerebroside (GalC), i.e., A007/O4+GalC-] to monoclonal antibodies R-mAb and O1 was studied both in culture and in vivo. In both cases staining with R-mAb shortly preceded that with O1; that is, a transient population of R-mAb+O1- cells was observed. R-mAb-O1+ cells were not detected. Differential staining with R-mAb and O1 was also noted at the subcellular level. In younger cultures in which R-mAb+ cells were first acquiring O1 immunoreactivity, many of these cells were stained by O1 only on the cell bodies and proximal portions of the processes, whereas in contrast R-mAb stained the whole cell, including the distal portions of the processes. Only in older, more mature R-mAb+ cells did O1 also stain the distal portions of processes. The expression of reactivity to R-mAb and O1 was compared to the proliferative capacity of the cells. Proliferation [assessed by bromodeoxyuridine (BrdU) incorporation] of both R-mAb+ and O1+ cells was negligible both in culture and in vivo. However, treatment of cells in culture with 10 ng/ml basic fibroblast growth factor resulted in an enhancement of proliferation of the R-mAb+ cells. Within the proliferating R-mAb+BrdU+ population, 80% of the cells were O1- (i.e., anti-galactocerebroside negative). These events occur during a critical period of development when A007/O4+ proligodendroblasts begin to become post-mitotic and express surface galactocerebroside.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433383 TI - Two-site enzyme immunoassay for beta NGF applied to human patient sera. AB - Nerve growth factor (NGF) supports sympathetic and sensory neurons in the peripheral nervous system and serves functions in the development and maintenance of cholinergic neurons in the basal forebrain. NGF distribution can be studied with the use of a sensitive two-site enzyme immunoassay (EIA). The monoclonal antibody 27/21 to mouse NGF was recently shown to effectively block the activity of both recombinant human NGF and native mouse NGF, and a two-site EIA using monoclonal antibody 27/21 was optimized. We have now applied this assay to examine NGF levels in normal human serum and serum from Parkinson, Alzheimer, and Huntington patients. To further test the specificity of conjugate binding, dilutions of the human sera were preincubated with an excess of monoclonal NGF antibody 27/21 in solution. With this strategy it was possible to completely block the signal obtained using the two-site EIA. Furthermore, we show that recombinant BDNF and NT-3 do not cross-react with monoclonal antibody 27/21 under our conditions. We found low levels of specific NGF immunoreactivity in normal human sera (0.4 +/- 0.1 ng/ml). Significantly lower levels of NGF were found in sera from patients with Parkinson's and Huntington's disease whereas sera from Alzheimer patients showed only slight reductions in the NGF level. Two patients who had received intracerebral NGF infusions (one with Parkinson's and other with Alzheimer's disease) showed significantly elevated serum levels of NGF during the period of infusion. Due to an inhibitory activity in human serum, it was impossible to demonstrate the low levels of NGF activity in the human serum samples using explanted embryonic sympathetic ganglia, even after concentration by pressure dialysis. Thus, the serum levels are below the limit to evoke a response in NGF-sensitive neurons and thus to expect any physiological effect. Nevertheless, the levels measured may be used as indicators in clinical conditions such as Parkinson's and Huntington's disease. PMID- 1433384 TI - Cell proliferation and protooncogene induction in oligodendroglial progenitors. AB - Cell proliferation and the expression of the protooncogenes c-fos and c-jun have been examined in the primary cultures of oligodendroglial (OL) progenitor cells in response to phorbol 12-myristate 13-acetate (PMA), serum, insulin, insulin like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF). Combined [3H]thymidine autoradiography and immunocytochemistry was used to assess the mitogenic response of O4 (an oligodendrocyte-specific marker)-positive OL progenitors. In addition, the rate of DNA synthesis was measured by the incorporation of [3H]thymidine into acid precipitable material. It was found that all of the agents tested stimulated DNA synthesis in OL progenitors and induced a rapid increase in c-fos and c-jun protooncogene expression. The induction of c-fos gene expression and DNA synthesis in response to PMA was completely blocked by 1-(5-isoquinolinyl sulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C (PKC), thereby suggesting a role for PKC in the control of c-fos expression and cell proliferation in OL progenitors. PMID- 1433385 TI - Microtubule-associated protein tau is required for axonal neurite elaboration by neuroblastoma cells. AB - NB2a/d1 neuroblastoma cells constitutively express multiple isoforms of the microtubule-associated protein tau and incorporate this protein into the axonal neurites elaborated during serum deprivation. To examine whether or not tau played an essential role in axonal outgrowth, cells cultured in serum-free medium were treated at 24 h intervals with antisense- and sense-oriented cDNA oligonucleotides (25 or 36 mers that span or are upstream of tau initiation codon) and were simultaneously serum deprived. Oligonucleotide uptake was confirmed by determination of intracellular levels of radiolabeled oligonucleotides. Treatment for 48 h with tau antisense oligonucleotides reversibly inhibited the expression of tau and the number of neurite-bearing cells compared with treatment with sense oligonucleotides. By contrast, tubulin expression was not affected. When cells were treated with antisense oligonucleotide simultaneously with serum deprivation, the initial outgrowth of neurites was unaffected, but continued neurite elongation was prevented. By contrast, neurite outgrowth at 4 h was inhibited when cells were pretreated with tau antisense 24 h before serum deprivation. Furthermore, intracellular delivery of anti-tau antiserum prevented neurite outgrowth and, in cells that had previously been deprived of serum for 24 h, induced retraction of existing neurites. These findings indicate that both the initiation and the continued outgrowth of neurites are dependent on tau and that pre-existing cytoplasmic pools of tau can mediate initial neuritogenesis. PMID- 1433386 TI - EAE cerebrospinal fluid augments in vitro phagocytosis and metabolism of CNS myelin by macrophages. AB - Previous studies from this laboratory have shown that CNS myelin is phagocytized and metabolized by cultured rat macrophages to a much larger extent when myelin is pretreated with serum containing antibodies to myelin constituents than when it is left untreated or pretreated with non-specific serum. In this study the effect of cerebrospinal fluid (CSF) from rabbits with experimental allergic encephalomyelitis (EAE) in promoting myelin phagocytosis was examined. Fourteen rabbits were immunized with purified myelin in Freund's complete adjuvant, seven of which developed clinical EAE symptoms. Serum and CSF were collected from EAE and control rabbits, and the CSF was centrifuged to remove cells. Sera and CSF from these rabbits and from Freund's adjuvant-immunized controls and untreated controls were measured for IgG content by radial diffusion assay, their myelin antibody characteristics were analyzed by immunoblots, and the ability of these serum and CSF samples to promote myelin phagocytosis when used for myelin opsonization was examined. The ability of a CSF sample to enhance radioactive myelin uptake and phagocytosis by cultured macrophages as measured by the appearance of radioactive cholesterol ester was linearly proportional to its total IgG titer, and correlated approximately both with clinical symptoms of the animal and the presence of antibody against the myelin constituents myelin basic protein, proteolipid protein, and galactocerebroside. The cholesterol esterification activities of EAE sera correlated to a lesser extent with IgG levels and clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433387 TI - The morphological localization and biochemical characterization of a synapsin I like antigen in the nervous system of Aplysia californica. AB - Synapsins are a well-characterized class of phosphoproteins found at synapses in the mammalian nervous system. One member of this family, synapsin I, has been extensively studied and shown to associate in a phosphorylation-dependent manner with both small synaptic vesicles and cytoskeletal elements. Though the characteristics of synapsin I suggest an important function in synaptic transmission, its definitive role is still in question. In an effort to find a model system in which to test directly the function of synapsin I, we have looked in the nervous system of the marine mollusc Aplysia californica for synapsin I like antigens (SILA). Light microscope immunocytochemical studies using polyclonal and monoclonal antibodies to bovine brain synapsin I demonstrate Aplysia SILA in neuronal somata, in the neuropil, and at some identified synapses. Though SILA were exclusively associated with neuronal structures in Aplysia, the pattern of staining suggested that they are not present at all synaptic terminals. This interpretation was corroborated by ultrastructural studies in which SILA were present at some synaptic terminals but absent, or in low abundance, in adjacent terminals. In axons, SILA were associated with vesicles of 120-150 nm diameter, as well as with filamentous structures. Biochemical studies identified small amounts of SILA of 40 and 50 kD molecular weight that are recognized by several antibodies to mammalian synapsin I, and are acid extractable, collagenase-sensitive phosphoproteins; these are criteria used to define synapsin I homologues in other species. Our studies indicate that SILA are present in neurons in Aplysia californica but suggested that they represent only a small percentage of the total protein within the nervous system. PMID- 1433388 TI - Enhanced permeabilities of cationized-bovine serum albumins at the blood-nerve and blood-brain barriers in awake rats. AB - Permeability-surface area products (PAs) of the blood-nerve barrier (BNB) and blood-brain barrier (BBB) to 125I-labeled native bovine serum albumin (nBSA, pI approximately 4), and to 2 cationized albumins (cBSA) of differing pI (pI approximately 8 and 11), were quantitatively determined in awake rats, using an i.v. bolus injection technique. Mean PAs of the BNB and BBB to 125I-nBSA, after a circulation time of up to 120 min, were (0.17 +/- 0.23) and (0.09 +/- 0.05) x 10( 5) ml/s.g. wet wt, respectively (n = 12 rats), and were not significantly different from 0 (P greater than 0.05). Mean PAs of the BNB and BBB to 125I-cBSA (pI approximately 8), after circulation time of 12 min, were (1.9 +/- 0.1) and (1.7 +/- 0.1) x 10(-5) ml/s.g wet wt, respectively (n = 8). Significant greater PAs, at both the BNB and BBB to 125I-cBSA (pI approximately 11) [(8.2 +/- 1.8) and (3.0 +/- 0.6) x 10(-5) ml/s.g wet wt, respectively (n = 12)], than both PA's of nBSA and cBSA (pI approximately 8) were found. The accumulation of 125I-cBSA in epi-perineurial tissues also was higher than that of 125I-nBSA, and was related to the degree of cationization. Our results indicate that, as at the BBB, the transfer of cationized serum albumin is enhanced over that of native albumin at the BNB of the mammalian peripheral nerve. PMID- 1433389 TI - Immunocompetent cell markers in human fetal astrocytes and neurons in culture. AB - During the past few years, evidence has accumulated that interaction with peripheral immune cells as well as immunoregulatory functions in the central nervous system (CNS) can be played by several types of brain resident cells. Since very little information is available in man, however, we investigated the presence of markers so far considered typical of immunocompetent cells in in vitro cultures of human fetal brain. Immunocytochemistry at the light, scanning, and transmission electron microscopic levels revealed positivity for a very restricted range of macrophage antigens in astrocytes, which, however, were incapable of phagocytosis. In particular, expression of the major histocompatibility complex-class II antigen HLA-DR was observed in the cytoplasm and on the cell surface of GFA-P+ astrocytes and increased with time in culture and cell passages. Among the T-lymphocyte markers tested, Thy.1 and CD4 were positive. Both neurons and astrocytes carried Thy.1 from early cell passages. Noteworthy was the presence of CD4, which serves as the receptor for AIDS virus, in neurons from the first 2 weeks, whereas astrocytes became positive after only 4-6 weeks. Even if most staining was in the cytoplasm, some was exposed on cell surface. Astrocytes were found positive for the B-lymphocyte marker CD21, the cellular receptor for Epstein-Barr virus, whereas CD24 was detected in both neurons and astrocytes. Both antigens are related to B-cell proliferation. Results are in favour of the hypothesis of human brain cells being actively involved in CNS immunological events. PMID- 1433390 TI - Nerve growth factor receptor gene expression in human peripheral blood lymphocytes in aging. AB - Nerve growth factor (NGF) has a modulating effect on immune function, which may occur as a consequence of binding to the NGF receptor (NGF-R). To determine if mRNA for the gene coding for p75NGFR (low affinity NGF-R) is present in lymphocytes, Northern blot analysis of mRNA from human peripheral blood lymphocytes (PBL) and purified T lymphocytes was initiated using cDNA probe for human p75NGFR. p75NGFR mRNA was present in PBL and T lymphocytes, and the mRNA in response to phytohemagglutinin stimulation showed maximum levels at 14 hr of stimulation. p75NGFR mRNA content when analyzed in PBL and T cells from volunteers of various ages showed that p75NGFR mRNA expression does not change with the age of the cell donor. PMID- 1433391 TI - Effect of dark rearing on the volume of visual cortex (areas 17 and 18) and number of visual cortical cells in young kittens. AB - The surface area, total volume, and total number of neurons of areas 17 and 18 in one hemisphere of dark-reared (DR), dark-reared and light-exposed (DRL), and normally reared (NR) kittens were studied at the age of 6 weeks. The thickness of the visual cortex was lower by 13% and 11% (area 17) and by 17% and 16% (area 18) in DR and DRL groups, respectively, when compared with similar cortical areas in NR kittens. The surface area values of area 17 were nearly the same in DR and DRL kittens, both being, however, 37% smaller than in NR animals. The surface area of area 18 was significantly smaller than that of area 17 in each group, and was also lower in DR (by 27%) and DRL (by 21%) groups when compared with the NR group. As a consequence of dark rearing, the numerical density of cortical neurons in area 17 amounted to about double of the value observed in normally reared kittens and was also significantly higher in area 18. The numerical density of nerve cells of DRL kittens fell between the DR and NR groups. The total cortical volume of area 17 was similar in DR and DRL groups but it was by 46% (DR) and by 44% (DRL) smaller than in NR kittens. In each experimental group, the total volume of area 18 was significantly smaller than that of area 17. The cortical volume of area 18 was also smaller than in the NR group by 39% and 34% in DR and DRL groups, respectively. In DR and NR kittens, the total numbers of neurons in areas 17 (DR = 26.4 million, NR = 25.7 million) and 18 (DR = 8.5 million, NR = 9.0 million) were essentially similar. In the DRL groups a significantly smaller number of cortical neurons was found both in area 17 (21.5 million) and in area 18 (6.8 million). It is concluded that, in spite of considerable differences in the cortical thickness, surface area, numerical density, and total cortical volume, the absolute numbers of neurons in area 17 and 18 of visually deprived (DR) and NR kittens do not differ at 6 weeks of age. The main deficit in cortical organization following dark rearing, therefore, appears to be confined mainly to the neuropil, as a result of an underdevelopment of neuronal processes and of depressed synaptic organization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1433392 TI - Guidelines for trauma care fellowships. American Association for the Surgery of Trauma and the Committee on Trauma of the American College of Surgeons. PMID- 1433393 TI - The effect of the new trauma DRGs on reimbursement. AB - Reimbursement for trauma care based on prospective payment has not been satisfactory. The Health Care Financing Administration introduced four new Multiple Significant Trauma (MST) DRGs in 1991 with the intention of covering patients who have had at least two body sites injured. To determine the effect if any on reimbursement, a sample of patients who were assigned the new DRGs over a 5-month period were analyzed. The analysis compared the calculated reimbursement for these 49 patients based on their total accumulated charges, DRG weights, and the average Medicare dollar blend along with the additional weight factor specific for the study facility. This analysis was compared with an additional analysis determining the reimbursement performed on the same patient sample but with DRG weights determined from DRGs derived from the 1989 DRG GROUPER/FINDER. During the 5-month study period, 5.5% of the patients discharged from the hospital has sustained at least one injury covered by ICD-9-CM codes. Of these, 49 (3.9%) were classified into one of the four new MST DRGs. The majority of patients were male (75.5%), the mean age was 31.8 years, and the total charges accumulated were $1,809,192.23. The calculated DRG-based reimbursement was $1,183,495.40, or 65.5% of the total charges. In the second part of the study, using the DRGs available in 1989 for the same sample of patients, the DRG-based reimbursement was $691,437.72, or only 38.2% of the accumulated charges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433394 TI - Invalidation of the APACHE II scoring system for patients with acute trauma. AB - The APACHE II scoring system has been promulgated as a useful tool in the assessment of the severity of injury and prognosis for acutely ill patients. The physiologic basis for stratification is weighted toward older patients with chronic medical conditions. Recently, the APACHE II system has been proposed as a method for determining diagnosis related group (DRG) reimbursement for individual trauma patients. The present study applied the APACHE II scoring system to 280 patients with blunt or penetrating trauma who had documented systolic blood pressure < 90 mm Hg. Fifty-seven (20%) died of their injuries within the first 24 hours. APACHE II scores were recorded both in the emergency room (ED) and at 24 hours following admission. Injury Severity Scores (ISS), Revised Trauma Scores (RTS), and TRISSCAN were calculated. The APACHE II (n = 223) recorded at 24 hours (2.5 +/- 0.2) was significantly less than that recorded in the ED (6.6 +/- 0.3, p < 0.05, Mann-Whitney analysis). Using regression analysis, there was no correlation between APACHE II and ISS if recorded in the ED (r2 = 0.06) or 24 hours following admission (r2 = 0.08). APACHE II also demonstrated a poor correlation with the length of hospital stay (r2 = 0.03 [ED], = 0.19 [24 hours]). Whereas APACHE II may be helpful in defining severity of disease among patients with acute-on-chronic medical conditions, the classification lacks an anatomic component, which is essential to assess the magnitude of acute injury in patients who are typically otherwise healthy. PMID- 1433395 TI - The management of gunshot wounds to the face. AB - Treatment principles for penetrating neck trauma are well described yet few exist for facial injuries. To help delineate these issues, we viewed our recent experience with gunshot wounds to the face. Since 1986 we have treated 100 patients with such injuries. Their mean age was 28.9 years (range, 12-77 years). There were 89 male patients and 11 female patients. Ninety-six patients were considered stable on initial examination. Yet 35 patients required urgent airway control in the ED; only two needed a surgical airway. Emergency angiography was performed in 37 patients; 19 vascular injuries were identified. Eleven required therapy for vascular injuries, five by neck exploration and six by embolization. In 15 patients the trajectory suggested an intracranial injury, i.e., across the base of the skull. Although 14 of 16 patients were awake and alert at examination, head CT scans demonstrated serious intracranial pathologic processes in 9 patients. Sixty-seven patients sustained bony injury, 19 patients a significant nonvascular soft-tissue injury, and 38 patients a significant neurologic injury (26 peripheral, one spinal and 20 cerebral injuries). Ultimately, 44% of all patients required some surgical treatment and 25% had a complication from their injury. Six patients died, three of CNS injury, one of exsanguination, and two of sepsis. The bony, soft tissue, nervous, and vascular anatomy make the management of gunshot wounds to the face challenging. Although initially stable, many patients require early airway control and urgent work-up for vascular and intracranial injuries. Early subspecialty input is helpful in delineating the often complex injury pattern and planning an optimal management strategy. PMID- 1433396 TI - Utilization of trauma-related deaths for organ and tissue harvesting. AB - A randomized retrospective analysis of patients who suffered trauma-related deaths over 36 months (May 1987-April 1990) was performed to study their utilization as candidates for organ and tissue harvesting. There were a total of 108 patients: 79 males, 29 females. The average age was 46.2 years; 38 (36%) of these patients were 65 years of age or older. Over 50% of fatalities were the result of motor vehicle crashes. There were 61 potential tissue donors. Forty three were lost without documentation of a request for organ procurement. There were 23 patients with potentially salvageable organs: one candidate was lost without documentation of a request for organ procurement. Twenty-eight (26%) of the patients had support withdrawn; 16 were 65 years old or older. Brain death protocol was instituted in 17 (20%); organs were obtained from 70% of these patients. Reasons for failure of procurement after request by a physician included family refusal in seven cases, cardiopulmonary arrest during brain death protocol in two cases, and religious bias in one candidate. Twelve patients were organ donors: 10 patients were tissue donors. We conclude that the greatest source of underutilization lies in the failure to request tissue for harvesting, since there were no isolated tissue donors. Pertinent information should be more widely distributed to physicians regarding candidacy for tissue donation. Further consideration of the adequacy of organs or tissue in relation to the candidates' age should be given, since patients aged 65 years and older can be a significant source of potential donor candidates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433397 TI - Could the oxygen cost of breathing be used to optimize the application of pressure support ventilation? AB - Pressure support ventilation (PSV) is a new ventilator modality that augments spontaneous inspiratory pressure with selected levels of positive airway pressure. There is presently considerable interest in its use in the management of critically ill, ventilator-dependent patients. The optimal method for application has not yet been established. This study investigated the effects of PSV on the oxygen cost of breathing (OCOB), a clinically applicable technique for quantitating the work of breathing. The OCOB and other bedside variables of pulmonary function were measured during PSV in ventilator-dependent patients where weaning was limited by an inability to sustain respiratory work. Nine studies were performed in 8 patients in the surgical intensive care unit. The OCOB, tidal volume (VT), respiratory rate (RR), and minute ventilation (VE) were measured at various levels of pressure support. The OCOB was calculated from the difference in oxygen consumption (VO2) during mechanical and spontaneous ventilation both at CPAP and with PSV. With increasing levels of PSV, the OCOB was observed to steadily decrease from 22% to 8% (p < 0.001). There were also statistically significant increases in VT and decreases in RR. VE appeared not to be influenced. The results of this study suggest that the bedside measurement of the OCOB may be an accurate, simple, and reproducible method of titrating the level of applied pressure support in order to optimize respiratory work. PMID- 1433398 TI - Continuous pulse oximetry and the diagnosis of pulmonary embolism in critically ill trauma patients. AB - The diagnosis of pulmonary embolism (PE) may be difficult to establish in trauma patients, particularly those who are unresponsive or mechanically ventilated. Based on a prior retrospective study, we hypothesized that patients monitored by continuous pulse oximetry who experienced a 10% or greater sudden sustained drop in arterial oxygen saturation (SaO2) without a change in static lung compliance (Cst) were most likely to have had a PE. We followed SaO2 in 972 patients admitted to our trauma ICU during the 18-month period ending in December 1990. Forty-eight patients (5%) with SaO2 changes, but no Cst changes, were evaluated for suspected PE using pulmonary arteriography (PA). Of these, 21 (44%) had a positive PA study. All patients with a positive PA had either clear chest roentgenograms or no change in underlying pulmonary pathologic processes. Of the remainder, 26 had evidence of a new pathologic entity on chest roentgenograms and only one patient had a SaO2 decrease, no change in Cst, and a negative PA. All mechanically ventilated trauma patients should have SaO2 monitored continuously. Patients with a > 10% drop in Sao2 with no change in Cst and no new roentgenographic chest findings should undergo PA. Based on our experience, this approach would yield a sensitivity, specificity, and predictive value of 100%, 99.9%, and 95%, respectively, for the diagnosis of clinically significant PE. PMID- 1433399 TI - Venous injuries of the lower extremities and pelvis: repair versus ligation. AB - Many surgeons advocate repair of venous injuries to prevent the sequelae of venous ligation. Since 1986, we have treated 74 patients with 79 venous injuries of the lower extremity or pelvis. There were 68 men and six women with a mean age of 29.2 years (range, 16-62 years). The mechanisms of injury were gunshot wounds in 61 patients, stab wounds in 11 patients, and shotgun wounds and blunt trauma in one patient each. Forty-eight injuries were treated by ligation; 31 injuries were treated by repair. Repairs included two interposition grafts, eight end-to end repairs, 16 venorrhaphies, and five vein patches. In addition, we developed a venous injury staging system (VIS), which ranged from grade I (less than 50% laceration) to grade IV (complete interruption with soft-tissue injury). Patient age, mechanism, location of injury, associated injuries, and incidence of arterial injury were not different between the patients treated by ligation and those treated by repair. Patients treated with venous ligation had a greater VIS (mean, 3.45 vs. 2.0), a greater incidence of shock (71% vs. 39%), and higher transfusion requirements (9.23 vs. 4.82 units). Postoperative morbidity rates were identical, however. There was no increase in the need for fasciotomy in patients treated with venous ligation. Eighty-six percent of the patients treated by ligation were totally free of edema at discharge. The others had only mild edema that did not interfere with daily activities at discharge and follow-up. Ligation is a safe alternative to repair in patients with injuries to the lower extremities or pelvis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433400 TI - Trauma center closures: a national assessment. AB - A 1990 national survey of 66 closed trauma centers across 14 states was conducted to ascertain the factors that prompted closure. Data from 44 facilities, or 67% of the centers identified, indicate that inadequate financing and physician participation were commonplace. The findings support the work of other investigators and demonstrate that uncompensated care, inadequate reimbursement, high operating costs, and lack of physician support all adversely affect trauma care in both urban and suburban settings. PMID- 1433401 TI - On-scene helicopter transport of patients with multiple injuries--comparison of a German and an American system. AB - Hospital-based helicopter services from a German (GER) and an American (AMR) university-affiliated trauma center were reviewed. All patients with multiple injuries transported via helicopter from the scene to the trauma centers during a 1-year period were included. The patients were comparable regarding mechanism of injury, age, flight times, mean ISS, ISS distribution, and number of severe injuries per body region (patients with AIS score > 3 for head, thorax, and abdomen). Overall mortality was 21 of 221 (9.5%) for GER and 21 of 186 (11.3%) for AMR (NS). Survivor-based TRISS analysis yielded Z statistics of +2.459 for GER (p < 0.025) and +1.049 for AMR (NS). M statistics were 0.89 for GER, 0.874 for AMR; the W statistic +1.35 for GER. There were nine unexpected survivors (Ps < 0.50) for GER and six for AMR. There was a significantly higher (p < 0.01) number of early deaths (< 6 hours) in AMR (12; ISS = 56) than in GER (four; ISS = 64). Analysis of the prehospital data demonstrated significant differences in the mean volume of IV fluids infused: 1800 mL, GER; 825 mL, AMR (p < 0.05); rate of intubation: 82 of 221 (37.1%) GER; 24 of 186 (13.4%) AMR (p < 0.001); and thoracic decompressions: 20 of 221 (9.1%) GER; 1 of 186 (0.5%) AMR (p < 0.001). Prehospital care in the GER system is directed on scene by a trauma surgeon member of the flight crew compared with a nurse/paramedic team with remote medical control in the AMR system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433402 TI - Initial and subsequent hospital costs of firearm injuries. AB - OBJECTIVE: To provide economic, epidemiologic, and clinical data on initial and subsequent hospitalizations for firearm injuries. DESIGN: Nonconcurrent prospective study; data obtained by medical records review. SETTING: Public university teaching hospital, designated a level I trauma center. SUBJECTS: Two hundred fifty persons first hospitalized for firearm injuries at UC Davis Medical Center, Sacramento, between January 1, 1984, and June 30, 1985, and followed by medical records review to June 30, 1989. RESULTS: The aggregate hospital charge for 250 firearm injuries, exclusive of professional fees, was $3,745,496, of which 80% was borne directly or indirectly by public funds. The charge for initial hospitalizations was $3,297,506. Mean and median initial charges per case were $13,190 and $5,996 respectively; range, $787-$494,152. The five patients with charges over $100,000 accounted for 33% of all charges; 36% of all patient days were attributable to the eight patients with hospitalizations lasting more than 30 days. Thirty-one patients were rehospitalized a total of 71 times; charges for rehospitalization totaled $447,990. Three fourths of all charges resulted from handgun injuries. CONCLUSIONS: The costs for hospital treatment of firearm injuries are substantial. Avoiding prolonged hospitalization may be helpful in controlling these costs, but will be difficult to achieve. Primary prevention of firearm injuries may be the most effective cost-control measure. PMID- 1433403 TI - Differential effects of cyclo-oxygenase and thromboxane synthetase inhibition on ventilation-perfusion relationships in acid aspiration-induced acute lung injury. AB - Cyclo-oxygenase metabolites are important regulators of pulmonary vascular and airway tone and may act to regulate ventilation-perfusion (VA/Q) relationships. Hypoxemia that follows aspiration of gastric acid is associated with increased venous admixture, and plasma levels of thromboxane (TX) B2 and 6-keto-PGF2 alpha are increased after experimental acid-induced acute lung injury. The present study was designed to determine the effects of cyclo-oxygenase metabolites on VA/Q relationships in canine acid aspiration. Eighteen anesthetized dogs received 0.2 mL/kg 0.1 N HCl intratracheally; six were pretreated with ibuprofen (IBU), a cyclo-oxygenase inhibitor, 12.5 mg/kg IV, and six other dogs received OKY-046 (OKY), a TX synthetase inhibitor, 0.5 mg/kg IV. The remaining six animals (ACID) served as controls. Continuous distributions of ventilation and perfusion were evaluated with the multiple inert gas elimination technique. Within 30 minutes, acid injury resulted in significant (p < 0.05) decreases in PaO2 from baseline values by 44.7 +/- 5.4 and 47.6 +/- 4.8 mm Hg in the ACID and OKY groups, respectively. Although decreased, the change in PaO2 of 21.0 +/- 4.8 mm Hg in IBU animals was significantly (p < 0.05) attenuated in comparison with the other groups. Ibuprofen increased pulmonary vascular resistance, attenuated perfusion to shunt and low VA/Q areas, and reduced ventilation to unperfused areas for the first 2 hours after acid injury (all p < 0.05), whereas OKY exacerbated hypoxemia and VA/Q inequality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433404 TI - Lethal Staphylococcus aureus-induced shock in primates: prevention of death with anti-TNF antibody. AB - A successful experimental treatment for gram-positive sepsis to our knowledge has not been achieved. The objectives of this study were to develop a nonhuman primate model of lethal gram-positive sepsis employing the micro-organism Staphylococcus aureus and to determine the efficacy of treatment using monoclonal antibody (MAb) to tumor necrosis factor alpha (TNF). The antibody was administered intravenously, 15 mg/kg, 30 minutes after the beginning of a 2-hour infusion of S. aureus, 4 x 10(10) colony forming units/kilogram. The baboons infused with S. aureus demonstrated the release of the cytokines TNF and interleukin-6 (IL-6), but endotoxin was not observed in the plasma at any time. Treatment with antibody to TNF abolished the rise in serum TNF levels and reduced the increased levels of IL-6. Treatment with MAb to TNF prevented multiple organ failure and achieved permanent (> 7 day) survival of all baboons. PMID- 1433405 TI - Pulmonary damage after intramedullary femoral nailing in traumatized sheep--is there an effect from different nailing methods? AB - Stabilization of femoral shaft fractures is a controversial issue in the management of patients with multiple trauma. Intramedullary nailing usually is preferred primarily; in recent years, however, pulmonary complications (e.g., ARDS) have been reported that were attributed to the reaming procedure. To study the effects of different nailing methods in a model of severe trauma, hemorrhagic shock and lung contusion were created at day 1 in sheep prepared by the method described by Staub. After recuperation (day 3) the animals in the study group (group 1) underwent intramedullary nailing of a closed femur without prior reaming; group 2 was treated with reaming and nailing according to AO standards. The reaming procedure led to an acute increase of pulmonary arterial pressure only in group 2 (19.8 +/- 2.1 to 31.0 +/- 4.6 mm Hg). Pulmonary triglyceride levels increased at parallel time points from 18.27 +/- 2.3 to 33.04 +/- 7.37 mg/dL only in group 2. Stimulatory capacity of polymorphonuclear leukocytes (PMNL) increased in the study group and decreased in controls (group 1: 2.652 +/- 0.23 x 10(6) cpm to 3.387 +/- 1.34 x 10(6) cpm; group 2: 2.699 +/- 0.34 x 10(6) cpm to 2.460 +/- 0.187 x 10(6) cpm). Intramedullary nailing caused an increase of lung capillary permeability in both groups; in the study group less damage was seen (group 1: 0.390 +/- 0.0006 to 0.354 +/- 0.011; group 2: 0.391 +/- 0.0004 to 0.336 +/- 0.015; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433406 TI - Cost and complications during in-hospital transport of critically ill patients: a prospective cohort study. AB - We prospectively studied transport of a group of 100 surgery/trauma patients and a matched control group in the ICU. APACHE II scores for the two groups were 23 +/- 6 and 20 +/- 8. During transport both groups had ECG, heart rate, blood pressure, and oxygen saturation continuously monitored. We also determined the cost and results of transport for those patients requiring diagnostic testing. There were six diagnostic tests performed: CT scan of the abdomen (39%), CT scan of the head (31%), CT scan of the chest (8%), CT scan of the cervical spine (4%), angiography (14%), and tomography (4%). Average transport time was 74 +/- 16 minutes with a range of 20-225 minutes. Physiologic changes defined as a BP +/- 20 mm Hg, heart rate +/- 20 beats/min, respiratory rate +/- 5 breaths/min, or oxygen saturation +/- 5% for 5 minutes duration occurred in 66% of transported patients and 60% of ICU patients. There were no differences in arterial blood gas levels before and during transport. In 39% of transports, the results of diagnostic testing produced a change in patient management within 48 hours. Abdominal CT scanning and angiography were associated with the highest percentage of tests leading to a management change (51% and 57%). The average charge to the patient was $612.00 and the average cost to the hospital $452.00. Our results suggest that while physiologic changes are frequent during transport, they are also frequent in ICU patients as a consequence of the severity of illness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433407 TI - An evaluation of provider-related and disease-related morbidity in a level I university trauma service: directions for quality improvement. AB - As the number of preventable trauma-related deaths plateaus as a result of trauma system development, new directions for quality improvement in trauma care must come from analyzing morbidity with standardized methods to establish thresholds for provider-related and disease-specific complications. To establish such thresholds and determine priorities for improvements in quality all trauma patients who died, who were admitted to the ICU or OR, who were hospitalized for more than 3 days, or who were interfacility transfers to an academic trauma service, were concurrently evaluated for 1 year. All complication events were defined, reviewed, tabulated, and classified using 135 categories of complications. These categories were subdivided into provider-specific and disease-specific complications. Provider-related complications were classified as justified or unjustified to allow identification of events with a potential for improvement. A total of 1108 patients were admitted (mean ISS, 17); there were 97 deaths. Three potentially preventable deaths were identified, 857 complication events were identified, and 285 provider-related complications were responsible for errors with potential for improvement in 59 events (21%). Disease-specific morbidity was primarily related to infection; pneumonia accounted for 36% of all infectious complications and systemic infection for only 8.6% of infectious complications. Organ failure and other major systemic complications occurred in 2%-8% of patients. This type of analysis forms the basis on which to determine thresholds of provider-specific and disease-specific morbidity in a trauma hospital and serves as a guide to direct efforts toward continuous quality improvement. PMID- 1433408 TI - A study of recovery in trauma patients. AB - Although the majority of trauma patients are discharged home rather than to a rehabilitation facility, the timeliness of their return to function (RTF) has received little study. The present prospective study attempted to identify those factors that would predict delayed RTF. The study group consisted of patients admitted to a level I trauma center for at least 24 hours, who were of working age (18-64 years), who passed a cognitive screening examination, and who were discharged home. Demographic data and psychological profiles were collected on all participants. Patients were followed by telephone at approximately 1 1/2, 3, and 6 months after discharge. Five hundred seventy patients were entered into the study; complete follow-up data were available for 441. Statistical methods were modeled after survival analysis using a proportional hazards multiple regression to identify variables prognostic of RTF time. This type analysis is independent of time, providing a "risk" of RTF at any point in time after the injury. It also allowed the calculation a relative hazards ratio (RHR), which quantifies the impact of a prognostic variable on RTF time. Injury Severity Score (ISS) and age were found to be associated with RTF (p < 0.0001 for each). After correcting for ISS and age, five additional factors were found to be associated with RTF. Higher educational level and living in a non-family household were associated with faster RTF. Less than 100% income replacement by disability income, pre-injury hostility, and litigation related to the injury were associated with slower RTF. There were a number of other demographic, work-related, and psychosocial factors that were not related with RTF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433409 TI - Management of trauma and emergency surgery in space. AB - Trauma may cause morbidity or mortality in expeditionary spaceflight settings. Physiologic and mechanical changes related to microgravity may increase susceptibility to and complicate the management of injuries in spaceflight. Limited surgical experience in microgravity suggests that special apparatuses and techniques will be needed to maintain the stability of patients, surgeons, and equipment, and to control fluids. A prototype microgravity surgical workstation and suction unit and modifications of standard procedures were devised to address these needs. Using these devices and methods and selected surgical supplies during repeated 25-second intervals of microgravity generated by parabolic arc flight, the "ABCs" of trauma management, limb traction and immobilization, and minor surgical procedures were performed in flight and problems were identified. Convincing "qualification" of spaceflight surgical equipment and protocols will require evaluations in continuous microgravity. As on Earth, the major determinant of emergency surgical care in spaceflight may be the presence or absence of a well-trained surgeon. PMID- 1433411 TI - Sagittal liver transection--an injury from improperly worn shoulder harness seatbelts: a report of two cases. AB - We have identified two cases which exemplify the typical injury caused by the under-the-arm placement of a shoulder harness (without the associated lap belt) in frontal collisions, namely, fatal liver laceration in the sagittal plane. Trauma care personnel should be alert for this type of rapidly fatal abdominal injury that occurs even in low-speed impacts. A prominent warning label on these belts regarding proper placement and the need for use of the associated lap belt may be appropriate. PMID- 1433410 TI - Duplex ultrasonography versus arteriography in the diagnosis of arterial injury: an experimental study. AB - Duplex ultrasonography (DUS) and arteriography (ART) were evaluated using an experimental model of arterial trauma in order to determine the accuracy of DUS compared with ART and to define the characteristic ultrasonographic features of arterial injuries. Occlusions (n = 19), blunt injuries (n = 24), lacerations (n = 25), arteriovenous fistulae (n = 13), or no injuries (sham, n = 19) were surgically created in the femoral and carotid arteries of 25 dogs. Following closure of the incisions, DUS was performed and interpreted by a staff vascular surgeon without knowledge of the presence or type of injury. Biplane selective ART was evaluated by an independent staff radiologist. Although DUS and ART were equally accurate in evaluating arterial injuries, DUS was more sensitive (90.1% +/- 3.3% versus 80.2% +/- 4.4%, p = 0.002) and better at identifying lacerated arteries (p = 0.01). However, ART had greater specificity (94.7% +/- 5.1% versus 68.4% +/- 10.7%, p = 0.04) and was more accurate for identifying normal arteries (p = 0.04). The validity of DUS increased in the latter half of the study, thus demonstrating a learning curve. Duplex ultrasonography was a more sensitive screening modality than ART for evaluating arterial injuries in our experimental model, thereby supporting its use in clinical trials to evaluate its accuracy, reliability, and cost effectiveness in the trauma setting. Furthermore, management decisions can be based on the specific type of injury, pathologic condition of the arterial wall, and hemodynamic factors identified by DUS. Clinically occult arterial injuries can be followed by repeat DUS to define the natural history of these injuries. PMID- 1433412 TI - Profound hypothermic circulatory arrest. PMID- 1433413 TI - Pelvic suspension for the management of complicated perineal wounds. PMID- 1433414 TI - Wound infections after tornadoes. PMID- 1433415 TI - War in Croatia. PMID- 1433416 TI - Nonsurgical management of liver injuries. PMID- 1433417 TI - Effect of chronic hypoxia on fibronectin in plasma, bronchoalveolar lavage fluid and liver of rats. AB - The present study was undertaken to measure fibronectin (FN) concentration in plasma and bronchoalveolar lavage fluid (BALF) with an enzyme linked immunosorbent assay (ELISA) method, to observe the distribution of FN in liver with an immunohistochemical stain method and to investigate the effect of chronic normobaric hypoxia on them in experimental rats. The results showed that chronic hypoxia caused a significant decrease in plasma FN concentration while BALF FN concentration and the distribution of FN in the liver were not significantly affected, suggesting that the change in FN in the lower respiratory tract can not be reflected by the change in plasma FN concentration and that the decrease in plasma FN concentration can not be attributed to the change in liver FN secretion. The decrease in plasma FN concentration may lead to a decrease in the defence ability of the body and may contribute to the development of hypercoagulability observed in some patients with chronic hypoxia. PMID- 1433419 TI - Effects of dietary oils on pulmonary vascular reactivity and chronic hypoxic pulmonary hypertension in rats. AB - The effects of dietary oils on pulmonary vasoreactivity and chronic hypoxic pulmonary hypertension were assessed in rats fed on soybean oil (SO), pig oil (PO), soybean oil plus pig oil (SP) or a regular diet (HC) started two months before the onset of chronic normobaric hypoxia (10 +/- 0.5% O2 ventilation, 8 h per day, for 14 days). The mean pulmonary arterial pressure and pulmonary vasoreactivity to acute hypoxia were higher in the SO group than in the PO, SP and HC groups. Hypertrophy of the right ventricle in the SO group was more serious as well. Blood viscosity and hematocrit were augmented by chronic hypoxic in SO, PO, PS and HC groups, but no significant differences were found among them. The findings suggest that dietary soybean oil can potentiate hypoxic pulmonary vasoconstriction, and thereby promote the development of pulmonary hypertension and right ventricular hypertrophy. PMID- 1433418 TI - Analysis of the biocompatibility of magnetic porous tricalcium phosphate ceramics in rat femurs. AB - A new biomaterial, magnetic porous tricalcium phosphate ceramics (MPTCP), may be used for repairing defects in bones as a substitute for bone grafting. This study was designed to examine its biocompatibility and the systemic toxicity. The ceramic sections, approximately 15.3 mg, were implanted into both proximal femurs of 10 male and 10 female albino SW rats. An equal number of male and female animals served as sham-operated controls. Implantation of MPTCP ceramics in rat femurs had no deleterious effects on body weight, organ/body weight ratio, and on blood, liver and kidney functions. Plasma levels of inorganic phosphorus were significantly elevated in rats implanted with MPTCP ceramics. Alkaline phosphatase values in plasma in the experimental group were equal to those in the control group. Photomicrographs, radiographs and scanning electron photomicrographs of the rat femurs implanted with MPTCP ceramics demonstrated excellent bone association with implants and growth of some new bone into MPTCP ceramics. In conclusion, MPTCP ceramics are biocompatible and suitable for the reconstruction of bones. PMID- 1433420 TI - Prognostic significance of DNA flow cytometry in non-Hodgkin's lymphoma. AB - A series of cases of non-Hodgkin's lymphoma (NHL) were studied by morphology and flow cytometry. The DNA analysis was performed by applying a trypsin digestion method to archival paraffin-embedded samples. DNA aneuploid tumors constituted 47.4% of the total cases, and the frequency in the intermediate and the high malignant grade groups (51.9%, 76.8%) were significantly higher than that of the low grade group (17.6%; P less than 0.05). The S phase fraction (SPF) increased significantly with a high histological malignant grade (P less than 0.005). The mean SPF values of the low, intermediate and high grade lymphomas were 6.5 (0.6 18.8)%, 13.5 (3.2-37.3)% and 23.4 (4.4-41.4)%, respectively. Differences in ploidy status were not associated with survival rate. The survival rate of the cases with high SPF value in all cases of our series and low grade group of NHLs tended to become lower (P = 0.1 and 0.08, respectively). These results suggest that the flow cytometric analysis of DNA content should be a useful means for prediction of prognosis in non-Hodgkin's lymphoma. PMID- 1433421 TI - Effect of cigarette smoking on hypoxic pulmonary vasoconstriction and its relation to animal species and period of smoking. AB - The alteration in hypoxic pulmonary vasoconstriction (HPV) induced by cigarette smoking was studied in Wistar rats, piglets and in humans. The percentage change of pulmonary vascular resistance (delta PVR%) and the amplitude of the systolic wave in impedance pneumorheogram (delta H%) were used to estimate the strength of HPV. It was observed that immediately after acute cigarette smoking, HPV in rats increased (delta PVR% from 55.0 +/- 15.6% to 102.3 +/- 12.4%), which is mainly mediated by leukotrienes (LTs); whereas HPV in piglets decreased (delta PVR% from 65.2 +/- 12.5% to 55.9 +/- 9.8%), which is mainly mediated by beta-adrenergic receptors, and HPV in humans also increased (delta H% from 20.6 +/- 2.6% to 31.1 +/- 4.1%), in which prostaglandins and leukotrienes may play the role of mediators. However, after one-month cigarette smoking, the HPV in rats fell significantly (delta PVR% 11.4 +/- 1.6%). An increase in synthesis of vasodilative prostaglandins and a decrease in leukotrienes synthesis may be the contributing factors to this alteration in HPV. PMID- 1433422 TI - The chelating-resin modified electrode and its application in the detection of copper in human samples. AB - A new kind of carbon paste electrodes modified by chelating resin was prepared for detection of trace amount of copper in human hair. As the ion exchange between chelating resin and cupric ions and the coordination reaction on the modified electrode take place at the same time, this method has high sensitivity and good selectivity. The detection limit is 6 x 10(-9) mol/L. The average percentage of recovered copper is 108 +/- 8.3% and the variant coefficient (CV) 7.7%. PMID- 1433423 TI - A comparative study of the effects of cadmium on microsomal mixed-function oxidase activities between kidney cortex and liver. AB - The effects of cadmium and phenobarbital (PB) administration on the activities of microsomal mixed-function oxidase (MFO) in rat kidney cortex and liver were studied. Five indices, including cytochrome P-450 contents, aniline hydroxylase, NADPH-cytochrome c reductase, aminopyrine N-demethylase and 7-ethoxycoumarin O deethylase activities, were assayed. By comparison, it was found that PB could induce MFO activities in kidney cortex microsomes and liver microsomes, both hepatic and renal microsomal MFO were decreased by the ip injection of CdCl2, and Cd2+ could markedly decrease the phenobarbital induction to hepatic and renal microsomal MFO activities with the exception of NADPH-cytochrome c reductase in kidney cortex microsomes. PMID- 1433424 TI - Association between allotypes of complement components C2, BF, C4 of HLA class III and cerebral stroke. AB - Allotypes of C2, BF and C4 in 58 patients with cerebral stroke (CS) and 110 normal control individuals in Guangzhou district were determined. The results show that there is a significant association between BF*F and CS. PMID- 1433425 TI - A study of calcium ion-selective PVC membrane electrode based on neutral carrier N,n,n',n'-tetracyclo-3-oxapentanediamide (correction of oxapetanediamide). AB - A calcium ion-selective PVC membrane electrode based on neutral carrier n,n,n',n' tetracyclohexyl-3-oxapetanediamide, using di-(2-ethylhexyl)phthalate as the plasticizer and potassium tetrakis (4-chlorophenyl) borate as the additive is reported in this paper. The ion selective membrane consists of 1 wt% of the Ca2+ selective ligand, 65 wt% of the plasticizer, 1 wt% of the additive and 33 wt% of poly (vinyl chloride) powder. The electrode has the linear response range of 2.0 x 10(-7)-10(-1) mol/L with the Nernstian slope of 28 mV/decade at 25 degrees C and the detection limit of 2.0 x 10(-8) mol/L. The response time of the calcium ion-selective electrode is as the concentration of calcium ion is rapidly shifted from 10(-5) to 10(-4) mol/L. The potential stability and reproducibility are good. The free calcium in blood serum was determined by the calcium ion-selective electrode with satisfactory results. PMID- 1433426 TI - The preadministration of activated charcoal and aspirin absorption. AB - There is little information describing the effects of activated charcoal preadministration on drug absorption. This study was undertaken to determine the effect of activated charcoal preadministration at two different times on aspirin absorption. Fifteen volunteer subjects completed three study phases: 1) 975 mg aspirin alone, 2) 975 mg aspirin 30 min after 10 g activated charcoal, and 3) 975 mg aspirin 60 min after 10 g activated charcoal. Urine was collected for 48 h after the initiation of each study phase, and total aspirin recovery determined by HPLC. The aspirin recovery was 88.8% +/- 4.5% for the control phase, and 84.8% +/- 9.4% (Phase 1) and 85.8% +/- 12.6% (Phase 2) for the activated charcoal treatments (p > 0.05). These results suggest that activated charcoal administered 30 and 60 min prior to drug ingestion has little effect on drug absorption. Further studies of the effect of charcoal preadministration on the absorption of other drugs may provide useful information regarding factors important in determining activated charcoal efficacy. PMID- 1433427 TI - Ethylene glycol poisoning: experiences from an epidemic in Sweden. AB - In 1987 two lethal adult cases of accidental ethylene glycol poisoning were given spectacular attention in the Swedish mass media. This resulted in an epidemic of intentional ethylene glycol poisonings. In addition to six cases related to alcohol abuse, another 30 severe suicidal poisonings were reported to the Swedish Poison Information Centre in five months. The clinical course and outcome in these 36 severe cases are reviewed. The primary clinical manifestations were metabolic acidosis, CNS disturbances and kidney damage with circulatory failure in the most severe cases. Mortality was 17%. Fragmentation of the normal striation in heart cells was found in two of the fatal cases and severe brain damage in all fatal poisonings. The degree of acidosis but not the serum ethylene glycol level correlated with both kidney damage and outcome. Treatment included ethanol, correction of the metabolic acidosis and dialysis. Four patients with serum ethylene glycol concentrations of 10-20 mmol/L (620-1240 mg/L) but with no or minimal metabolic acidosis were treated with ethanol alone; none of these patients developed renal damage. PMID- 1433428 TI - Acute intoxication by endosulfan. AB - The authors report six patients with acute endosulfan intoxication. The symptoms of nausea, vomiting, headache, and dizziness began 2.7 +/- 0.5 h after ingestion; in four cases the patients had been hospitalized but were asymptomatic. All had severe metabolic acidosis with high anion gap and hyperglycemia; five of six had decreased blood platelets. Three patients had pulmonary aspiration, and five required mechanical ventilation. The one fatality followed acute renal failure, disseminated intravascular coagulation, thrombi in the pulmonary arteries and aorta, and cardiogenic shock. In this patient the blood endosulfan was 2.85 mg/L versus a mean of 0.48 mg/L in the survivors. PMID- 1433429 TI - The effects of histamine administered in fish samples to healthy volunteers. AB - The effects of histamine administered in samples of fish to eight healthy volunteers (4 females and 4 males), aged 21-30 years, were studied. The subjects were given 0, 45 and 90 mg of histamine that had been metabolized from histidine by photobacteria in the fish and 90 mg of histamine added to fresh fish, for breakfast. The subjects were observed during 6 h after breakfast. Special attention was paid to clinical symptoms, blood pressure and ECG. The pH of the gastric contents was recorded continuously from 5 min before to 6 h after the meal. Blood samples to measure the histamine concentration were taken at intervals during 24 h after breakfast. Two of the subjects showed effects (facial flushing, headache) that could be attributed to the ingestion of histamine. No significant changes were observed in the blood pressure and ECG. The pH of the gastric fluids did not decrease significantly. The histamine concentration in plasma correlated closely with the histamine dose ingested (p < 0.001, r = 0.996). The Cmax of the dose of 90 mg did not differ statistically significant from the Cmax of the dose of 90 mg histamine added to unspoiled fish. PMID- 1433430 TI - Review of parenteral sulfite reactions. AB - Sulfiting agents are commonly used in parenteral emergency drugs, including epinephrine, dexamethasone, dobutamine, dopamine, norepinephrine, phenylephrine, procainamide, and physostigmine. Published anaphylactic or asthmatic reactions have been associated with sulfited local anesthetics, gentamicin, metoclopramide, doxycycline, and vitamin B complex. The reactions differ from those caused by foods, in that they have a rapid onset, have no predilection for steroid dependent asthmatics, and do not always coincide with a positive oral challenge. The mechanism is unknown, but may involve a dose-related reaction with disulfide bonds on sympathetic and parasympathetic receptor membranes. Patients with a history of positive oral challenge to 5-10 mg of sulfite may be at increased risk of developing a reaction to parenteral sulfites. Despite documentation of sensitivity, sulfites should not be withheld from patients experiencing a life threatening emergency. Non-sulfited alternatives are often available, and should be used preferentially. PMID- 1433432 TI - Seizure with hyponatremia in a child prescribed desmopressin for nocturnal enuresis. AB - We report a case of hyponatremia associated with a grand mal seizure in a 28 month-old child after intra-nasal desmopressin administration for high fluid intake with nocturnal enuresis. In view of the temporary symptomatic action and the seriousness of certain side-effects of desmopressin we recommend that desmopressin be used with caution in childhood enuresis. PMID- 1433431 TI - Cocaine exposure in utero: perinatal development and neonatal manifestations- review. AB - The question of whether cocaine exposure in utero increases the risk of major structural malformations remains controversial. Most animal studies have demonstrated that cocaine can have a teratogenic effect. The ultimate association between cocaine exposure and fetal development must be inferred from human data. The relative effects of cocaine exposure, exposure to other illicit drugs and alcohol and deficient prenatal care are difficult to assess. Little specific information is available about the amount, duration, and timing of cocaine use during the nine months of pregnancy. Unlike the case with many other teratogens, cocaine exposure at any point in pregnancy can result in some abnormality. The extent of damage and the organ involved depend on the particular stage of morphogenesis. A large scale prospective human study is needed to confirm the suggested teratogenic effects. Since it involves an illicit drug such a study is obviously difficult to perform. PMID- 1433433 TI - Fatal systemic poisoning after skin exposure to monochloroacetic acid. AB - Little information is available on the toxicity of monochloroacetic acid. We report the case of a 38 year-old man who was splashed with an 80% monochloroacetic acid solution on 25-30% of his body surface. In addition to epidermal and superficial dermal burns, features of systemic poisoning occurred within a few hours including disorientation, agitation, cardiac failure and coma. He later developed severe metabolic acidosis, rhabdomyolysis, renal insufficiency and cerebral edema, and died due to uncal herniation on d 8. The 4 h post exposure plasma monochloroacetic acid concentration was 33 mg/L confirming skin absorption. In addition to its corrosive action, monochloroacetic acid probably blocks the tricarboxylic acid cycle (Kreb's cycle) and may also react with sulfhydryl groups in enzymes, causing severe tissue damage in energy-rich organs. PMID- 1433434 TI - The changes of gasoline compounds in blood in a case of gasoline intoxication. AB - A 44 year-old man, found in his gasoline vapor filled car, died of multiple organ failure on d 9. Blood samples from d 2-7 were analyzed by gas chromatography/mass spectrometry. The estimated half-lives of gasoline, toluene, ethylbenzene, m,p xylene, and o-xylene were 16.9, 21.4, 27.5, 32.8, and 25.8 h respectively. The estimated initial gasoline concentration in blood was 247 micrograms/ml. PMID- 1433435 TI - Clinical evaluation of workers handling melamine formaldehyde resin. PMID- 1433436 TI - Meprobamate intoxication: rare and difficult to find. PMID- 1433437 TI - Cerebral edema from valproate? PMID- 1433438 TI - Improvement of sexual behavior in aged rats by p-chlorophenylalanine and methysergide. AB - The effects of methysergide, a serotonin antagonist, and p-chlorophenylalanine (PCPA), a serotonin synthesis blocker on the sexual behavior of intact old male rats at 19-23 months of age and female rats at 17-18 months of age were studied. Female rats with prolonged vaginal cornification and a lordosis quotient (LQ) of less than 50%, and male rats displaying no ejaculation were selected as experimental animals. The receptivity of aged female rats, but not the approach behavior to males nor proceptivity was improved by PCPA or methysergide. The LQ of intact aged female rats in non-exit tests was improved by the i.p. administration of 50 mg/kg B.W. of PCPA 2 to 4 hours prior to the sexual behavior test or 3 mg/kg B.W. of methysergide 4 hours prior to the test. Total mount frequency and mount latency of intact aged male rats were improved by the administration of methysergide (3 mg/kg B.W.), while total mount frequency and intromission latency were improved by the administration of PCPA (20 mg/kg B.W. for 4 days). The present results together with the finding from our previous study suggest that the increase of serotonin (5-HT) activity per se plays an important role in the decline of receptivity of aged female rats and the copulatory activity of aged male rats. PMID- 1433439 TI - Molecular characterization of R-plasmids pST1 and pST2 from Salmonella typhimurium S24. AB - Salmonella typhimurium S24 was isolated in September 1986 at Kaohsiung Medical College Hospital, Kaohsiung, Taiwan, from a patient suffering from gastroenteritis during an outbreak of salmonellosis. Two conjugative R-plasmids have been isolated from Escherichia coli K-12 14R525, which was mated with S. typhimurium S24. The two R-plasmids found in S. typhimurium S24 belong to two different incompatibility (Inc) groups: the 130-kilobase IncFI plasmid pST1 and the 56-kb IncN plasmid pST2. These two R-plasmids of pST1 and pST2 together mediate resistance to multiple antibiotics in S. typhimurium S24. By DNA probes hybridization, plasmid pST1 was shown to carry an enteric type II chloramphenicol acetyltransferase (CAT) gene, a class C tetracycline resistance (TetR) gene and a type III dihydrofolate reductase (DHFR) gene, all of which confer resistance to chloramphenicol, tetracycline, and trimethoprim respectively. A Richmond's type III beta-lactamase gene was located on each plasmid of pST1 and pST2. beta lactamases specified by both plasmids pST1 and pST2 conferred high level resistance to amoxicillin, carbenicillin, piperacillin, sulbenicillin, ticarcillin in addition to ampicillin. A novel aminoglycoside 6'-N acetyltransferase [AAC(6')] was demonstrated on plasmid pST2. This AAC(6') enzyme modified kanamycin, amikacin, dibekacin, tobramycin, gentamicin, netilmicin, sisomicin, butirosin and ribostamycin. PMID- 1433440 TI - Carcinoma of the external auditory canal and middle ear. AB - Fifty-three patients with carcinoma arising in the external auditory canal and/or middle ear seen at Veterans General Hospitals, Taipei and Taichung in the period between January 1970 and December 1988 were retrospectively reviewed. There were 49 males and 4 females. Their ages ranged from 5 to 80 years, the average being 58 and the median 59 years. In 10 patients the primary site of the tumor was located in the middle ear, in 32 patients it was the external auditory canal, and in the remaining 11, both areas. The most common cancer which occurred in this area was the squamous cell type, accounting for 85% of our cases. The majority of patients had an otorrhea history with duration from 6 months to more than 40 years. Nine patients received surgery alone, 8 irradiation alone, 31 a combination of surgery and radiotherapy. Initial complete regression of the tumor was noted in 100% of the combined therapy group. This was better than surgery (56%) or irradiation alone (60%). Bleeding and infection caused by surgery, and osteonecrosis caused by radiation were the most frequent and severe complications. The actual 5-year survival rate was 33%. Life table analysis showed that only the extent of the disease affected survival significantly. The 5 year survival rates were 23% and 51% for advanced and early stages respectively (p < 0.05). Combined therapy resulted in better local control and survival than operation or radiotherapy alone, but the benefit did not reach a significant level (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433441 TI - [Interdigestive and postprandial pancreatic exocrine secretion and cholecystokinin release in dogs]. AB - Interdigestive and postprandial pancreatic exocrine secretion and cholecystokinin (CCK) release were investigated in 5 mongrel dogs with chronic gastric and pancreatic fistulas in this study. The rapidly exaggerated postprandial pancreatic exocrine secretions were shown to be directly correlated to the rapid CCK release after meal. Corresponding to the previous studies, in the interdigestive state, pancreatic exocrine secretion showed cyclic changes which would be abolished by intravenous administration of atropine sulfate. However, we failed to demonstrate any significant correlation between plasma CCK levels and periodic pancreatic exocrine secretions during the interdigestive state through CCK radioimmunoassay. Furthermore, intravenous administration of atropine sulfate did not change the plasma CCK levels significantly in the interdigestive state. Having reviewed the literature, we thought that the periodic pancreatic exocrine secretion during the interdigestive state might be related to motilin release and cholinergic enteropancreatic reflex. PMID- 1433442 TI - [Pattern shift visual evoked potentials in diabetes mellitus]. AB - Functional exploration of the optic pathways with pattern shift visual evoked potentials (PSVEP) has been rapidly accepted as a non-invasive method of investigation of diabetics. For this article, we conducted the PSVEPs study on 46 cases of NIDDM and 13 cases of IDDM. The peak latency, interpeak latency and evoked amplitude of P100 were analyzed in each case. For further correlation, the motor and sensory nerve conduction velocities of the median nerve, blood sugar, serum HbA1c, and duration of DM were measured simultaneously. Two nondiabetic control groups which matched the age and sex of the NIDDM and IDDM groups were used for comparison. In the IDDM group, the results showed prolongation of all peak and interpeak latencies (IPL) except the peak latency of N75 on the right side. The P100 amplitude was reduced as compared with the age-matched young control group. The interocular P100 latency difference (ILD) was not statistically significant between the IDDM group and the age-matched control group. The results of the NIDDM group revealed prolongation of all peak latencies and IPLs. The P100 amplitude and ILD showed no statistically significant difference between NIDDM and the age-matched control group. The prolongation of N 75 peak latency exhibited a linear correlation with duration, HbA1c and median nerve SNCV. PMID- 1433443 TI - [Surgical management of blunt liver trauma]. AB - From 1986 to 1990, 46 patients with blunt liver trauma were hospitalized and operated on in Kuang Tien General Hospital. Included were 33 males and 13 females with a mean age of 31 years (range: 2 to 62). The mean duration of the follow-up was 43 months. We classified the severity of liver injury with the liver injury scale which was published by the Organ Injury Scaling (O. I. S.) Committee of the American Association for the Surgery of Trauma (A. A. S. T.) in 1989. According to the operative findings, the liver injury of the 46 cases were classified as follows: grade I 4 cases, grade II 18 cases, grade III 16 cases, grade IV 2 cases, grade V 4 cases, and grade VI 2 cases. Among the patients, 4 cases were treated with drainage. Four cases underwent simple repair. Twenty-seven cases were treated with repair and drainage. Three cases underwent debridement and selective ligation of bleeding vessels. Four cases underwent partial resection of liver, and 3 cases required repair of the inferior vena cava. One case was packed with gauze for hemostasis. The mortality rate was 15.2%, and the morbidity rate 30.3%. The most frequent postoperative complications related to the hepatic injury in the patients who survived the initial operation were wound infection (8.7%), intra-abdominal abscesses (6.5%), pancreatitis (6.5%), pulmonary infection (4.3%), and small bowel obstruction (4.3%). PMID- 1433444 TI - Familial spontaneous pneumothorax-report of seven cases in two families. AB - Spontaneous pneumothorax usually occurs sporadically in healthy young adults, who tend to be tall and thin. The usual cause is rupture of small subpleural bullae found in the apex of the upper lobe. Familial spontaneous pneumothorax is a rare condition. With a review of the English literature from 1921 to 1991, only 59 families with 135 cases have been reported. A genetic background has been suggested, but the actual mode of inheritance is still unknown. Relationships between the HLA haplotype A2B40, the alpha1-antitrypsin phenotype and the occurrence of spontaneous pneumothorax have been proposed, but are still controversial. We present 7 patients in 2 families with 13 episodes of spontaneous pneumothorax. Neither congenital defect, alpha1-antitrypsin deficiency nor the described A2B40 HLA haplotype could be found in our patients. We propose that there are no such factors existed in these patients. Further study is required to determine if any genetic marker is linked to familial spontaneous pneumothorax. PMID- 1433445 TI - One result of marketing: breastfeeding is the exception in infant feeding. PMID- 1433446 TI - Field validation of the Tallstick in marginal communities in Nicaragua. AB - The Tallstick is a new, simplified anthropometric field tool which allows immediate visual interpretation of height-for-age. This tool was field tested in community-based programmes in Managua, Nicaragua, and the rural community of Los Zarzales, screening 1004 children aged 0-60 months for nutritional stunting. Overall sensitivity and specificity analysis comparing HAZ scores and Tallstick results revealed that the Tallstick correctly identified 83-85 per cent of severely stunted children (HAZ < -2.5) and two-thirds of those with HAZ of -2 and below. It also had good positive predictive value for the mildly stunted. As a screening tool for low weight-for-age, the Tallstick performed better than arm circumference. The best of the community volunteers trained with the Tallstick could use it as well as their trainers. Progressive stunting was found in the 280 children in the sample who did not receive any form of milk. The advantages of the Tallstick for community-level screening and the importance of sustained linear growth are discussed. PMID- 1433447 TI - Deletion analysis of DMD/BMD children in Singapore using multiplex polymerase chain reaction (PCR) technique. AB - Twenty-three children suffering from Duchenne/Becker muscular dystrophy (DMD/BMD) in Singapore were analysed using the multiplex polymerase chain reaction (PCR) technique. Deletions were found in 14 cases. One rare case of total deletion of all nine exons was observed. This is the first DMD/BMD deletion analysis on South East Asian children. This technique for screening deletions was informative in 61 per cent of the local cases and would be useful for rapid diagnosis of deletion cases of DMD/BMD. PMID- 1433448 TI - Breastfeeding promotion in Kenya: changes in health worker knowledge, attitudes and practices, 1982-89. AB - In 1982, a study of health worker knowledge, attitudes and practices with respect to breastfeeding was undertaken in Kenya. A breastfeeding promotion campaign ensued, in which training of health workers was a major component. In 1989, the impact of this campaign was evaluated through a survey examining changes in health worker knowledge, attitudes and practices. The survey showed that considerable improvements in knowledge and substantial improvements in hospital practices have occurred, although none of these could be attributed to any single element of the breastfeeding promotion programme. Particularly undesirable practices which were common in 1982, such as separation of mother and baby, formula feeding and use of bottles have virtually disappeared from Kenyan hospitals. Recommendations regarding future programme directions are made. PMID- 1433449 TI - Rutter's Behaviour Scale (B2) for children (Teacher's Scale): validation and standardization for use on Nigerian children. AB - Nigerian teachers were asked to place the children in their classes in either of two groups: Group I, comprising children of normal behaviour, and Group II, children who, in their opinion, had significant behavioural problems. Validity of the teachers' grouping was confirmed, using as reference measure the findings from traditional psychological assessment of the children. The teachers then completed the Rutter Child Behaviour Questionnaire (Teachers' Scale) for the same children. The children's scores on the Rutter Scale were matched against the teacher's grouping, the aim being to identify the Rutter Score that separates the children into two 'behaviour' groups that agree most closely with the teachers' own grouping. Results show that this was achieved at the Rutter Score of 10 (k = 0.66). Children scoring 10 or more on the Rutter scale appeared mostly in Group II, while those scoring less than 10 were mostly in Group I. Rutter's scale was also found to be a highly valid instrument for identifying Nigerian children with behavioural problems. It is recommended that Nigerian children scoring > or = 10 on Rutter's Behaviour Questionnaire (Teacher's Scale), should be regarded as children with behavioural disorder. This is one point higher than the score of > or = 9 recommended for British children. PMID- 1433450 TI - Detecting malnutrition at age 6-12 months: international comparisons of arm circumference v. standard anthropometry. AB - Growth faltering, which may herald protein-energy malnutrition (PEM) usually begins between ages 6 and 12 months. However, arm circumference (AC or MUAC) has mainly been used to screen for PEM between 12 and 60 months of age, when AC is age-independent. This study of 378 infants aged 6-12 months in Pakistan, Nepal, Sierra Leone, and Papua New Guinea showed that a cut-off 12.5 cm AC selects infants < 80 per cent weight-for-age (WA) with 76 per cent sensitivity and 90 per cent specificity. Of the 378 infants studied 131 (35 per cent) had WA < 80 per cent and 126 (33 per cent) had AC < 12.5 cm. Weight-for-length agreed less well with AC. The inter-regional prevalence range of AC < 12.5 cm was 29-40 per cent, while the WA < 80 per cent range was 27-45 per cent. When AC is plotted against age, a flat 'plateau' (slope = 0.04) shows age-independence between 6 and 12 months in these 378; this contrasts to the 10 per cent AC increase in European reference populations. Because this AC plateau parallels the WA plateau seen between 6 and 12 months of age in most developing nations, AC < 12.5 cm may provide a simple and valid screening test for early PEM in this crucial age bracket. Conformatory studies elsewhere are indicated. PMID- 1433452 TI - Women's work in agriculture and child nutrition in Tanzania. AB - This paper examines the food related work that women are doing, and the possible effect on child feeding and nutritional status. Women's participation in food production may have positive as well as negative consequences for child nutrition. On the one hand, it may augment the total amount of food procured, while on the other, it may give women less time for child care and feeding. The data show that women are using less time in cooking and children are fed less often during the peak labour seasons. However, a profound and conclusive negative effect of mother's agricultural work on child nutritional status could not be shown. This finding is explained by various compensatory mechanisms employed by the mothers which may buffer the negative effect of the women's time constraints. The norm of feeding children at the maximum only three times a day was seen as the major contributing factor to child malnutrition. According to the women, this feeding frequency was seen as the maximum possible taking into account their heavy work in agricultural production. PMID- 1433451 TI - Use of hepatitis B vaccine alone or in combination with hepatitis B immunoglobulin for immunoprophylaxis of perinatal hepatitis B infection. AB - The efficacy of hepatitis B vaccine alone or in combination with immunoglobulin in neonates born to HBsAG positive mothers was investigated. Twenty-four infants were given three doses (at 0, 1, 2 months) of the vaccine alone, while 27 infants were given hepatitis B immunoglobulin (HBIG) and three doses of the vaccine. Fifty-eight infants born to HBsAg positive mothers who did not agree for vaccination or could not come for follow-up constituted the control group. The overall seroprotection rates (anti-HBS levels > or = 10 IU/l) were almost similar in both the groups at 6 months (81 and 76 per cent, respectively). However, the seroprotection rates in babies born to HBeAg positive mothers were better with combination of HBIG and vaccine (71 v. 57 per cent, respectively). It was also observed that seroprotection rates in babies born to anti-HBe positive mothers were even better (100 and 90 per cent in vaccine alone and combination group, respectively). No chronic carrier was detected in babies born to anti-HBe positive mothers. PMID- 1433453 TI - Prenatal growth curves corrected for certain genetic and environmental factors. AB - Factor analysis for non-orthogonal data was done to assess the straight and interaction effects of certain genetic and environmental factors on birth weight. While the interaction effects did not assume any significance, straight effects of gestational age, parity, mother's weight, and sex were significant in influencing the birth weight. Mother's height and socio-economic status of the family had no significant effect on birth weight. Step-up multiple regression analysis showed that contribution to the total variance explained (R2 x 100 = 29.7 per cent) in birth weight was about 15, 7, 5, and 2 per cent, respectively, from gestational age, parity, mother's weight, and sex of the baby. Correction of the mean weight curve was done by successive graphic approximation method and residuals were further minimized. PMID- 1433454 TI - Gastric residuals in preterm babies. AB - The gastric residual (GR) volume was measured in 50 healthy preterm babies, 38 appropriate-for-dates (AFD), and 12 small-for-dates (SFD) with gestational age of 28-36 weeks. The mean basal 4-hour gastric residual (B4 GR) volume was 2.8 +/- 0.63 ml in parenterally fed babies. There was a marked decrease in the residuals from 20.7 +/- 15.2 per cent (mean +/- SD) on day 4 to 8.6 +/- 4.3 per cent on day 7 (P < 0.001). Of the 27 infants fed with expressed breastmilk (EBM), mean GR was 24.4 +/- 10.2 per cent in supine and 12.8 +/- 4.3 per cent in prone position (P < 0.01). Twenty-one babies nursed in the prone position showed a mean GR volume of 12.8 +/- 4.3 per cent with EBM and 13.6 +/- 2.7 per cent with milk formula. No difference was noted in the gastric residuals of AFD v. SFD babies. No linear correlation was found between increase in abdominal girth and GR. However, if the increase in abdominal girth was at least 2 cm or more, a GR of 23 per cent or more was observed. This should be taken as warnings to reduce or withhold oral feeds. PMID- 1433455 TI - Beyond rehydration therapy: non-dehydration deaths from diarrhoea in children with malnutrition. PMID- 1433456 TI - Pitfalls in the diagnosis of malaria: a-parasitaemic severe malaria. PMID- 1433457 TI - Unchecked commercialization of ORS--a road to disaster? PMID- 1433458 TI - RUHSA--a model Primary Health Care Programme. PMID- 1433459 TI - Appraisal and peer review. PMID- 1433460 TI - Vertical jumping height and horizontal overhead throwing velocity in young male athletes. AB - The purpose of this study was to examine the effects of calendar and skeletal age, anthropometric dimensions, training history and their interactions on vertical jumping height and horizontal overhead throwing velocity in a cross section of 318 young male athletes (age range 9-16 years) participating in cross country skiing (n = 70), basketball (n = 40), apparatus gymnastics (n = 19), ice hockey (n = 50), track and field (n = 89) and wrestling (n = 50). Vertical jumping height was measured with four different loads held on the shoulders and then interpolated for loads representing 0 and 40% body mass. Horizontal overhead throwing velocity using both hands was determined for seven balls of different weights and then interpolated for weights representing 1 and 5% body mass. Both vertical jumping height and overhead throwing velocity were found to increase (P < 0.01) from the skeletally youngest to the oldest cohort when the effects of body height and mass were controlled. The inter-event comparisons did not reveal statistically significant differences in respect of vertical jumping height. Also in the overhead throwing tests, the inter-event differences were small, although the analysis of variance revealed statistically significant (P < 0.001) differences for the skeletal age cohorts of 13 and 14 years. While the quantity of training had no effect on vertical jumping height, it explained the results in the overhead throwing test. The effects of training on vertical jumping and horizontal overhead throwing among adolescent athletes were considered to be small, while maturational processes and anthropometric development followed by increase in calendar age were deemed to be of greater importance. PMID- 1433461 TI - Ventilation and blood lactate increase exponentially during incremental exercise. AB - This study examined whether the ventilatory (V) compensation for metabolic acidosis with increasing O2 uptake (VO2) and CO2 output (VCO2) might be more in accord with the theoretical expectation of a progressive acceleration of proton production from carbohydrate oxidation rather than a sudden onset of blood lactate (BLa) accumulation. The interrelationships between V, VO2, VCO2 and BLa concentration, [BLa], were investigated in 10 endurance-trained male cyclists during incremental (120 +/- 15 W min-1) exercise tests to exhaustion. Regression analyses on the V, VCO2 and [BLa] vs VO2 data revealed that all were better fitted by continuous Y = A.exp.[B.VO2] + C rate laws than by threshold linear rate equations (P < 0.0001). Plots of V vs VCO2 and [BLa] were also non-linear. Ventilation increased as an exponential V = 27 +/- 4.exp.[0.37 +/- 0.03.VCO2] function of VCO2 and as a hyperbolic function of [BLa]. In opposition to the 'anaerobic (lactate) threshold' hypothesis, we suggest these data are more readily explained by a continuous development of acidosis, rather than a sudden onset of BLa accumulation, during progressive exercise. PMID- 1433462 TI - Morphological proportionality in elite age group North American divers. AB - The purpose of this investigation was to describe the morphological parameters that characterize elite age group divers. Comparisons are made to normative age group data from the Coquitlam Growth Study and the constancy of important characteristics from age group to age group is examined. Data were collected on 27 male and 28 female elite divers who participated in the 1990 North American Age Group Diving Championships. Body build, body composition and skinfold corrected diameters were determined from 36 anthropometric parameters and analysed by ANOVA, t-test and Phantom z-scores procedures. All age groups except the 14- to 15-year-old males were significantly (P < or = 0.05) shorter than their norms but recorded higher androgyny index values. The estimated relative muscle mass increased significantly (P < or = 0.05) with age for males at all ages (40.8-46.3%). The 16- to 18-year-old females had a significantly (P < or = 0.05) larger relative muscle component compared to the younger age groups (40.1 38.4%). When normalized for height, active tissue development of the extremities was comparable between the sexes except in the forearm. The results indicate that at all age levels short stature is an important characteristic for divers. Analysis of regional active tissue development provides further insight into sport-specific prerequisites for success at elite levels. PMID- 1433463 TI - The biomechanics of the discus throw: a review. AB - This review provides an evaluation of published scientific literature (mostly that in English or German) which has reported quantitative data relating to the biomechanics of the discus throw. This is done by considering the two stages of the throw--the launch (the movements in the circle) and the discus flight. To ascertain the optimal release characteristics of the discus to maximize the distance thrown, the results of those studies which have addressed this problem by simulating the flight of the discus are evaluated. To assess the merit of this literature, a detailed evaluation of studies of the aerodynamics of discus flight is also undertaken in this review. These results are compared with measured release conditions from filmed discus throws. The greater part of the review seeks to establish the technique of the thrower within the circle necessary to achieve an optimum release. Thus, the discus throwing technique is discussed in relation to the results of cinematographic data, and the extremely limited number of force platform and electromyographic studies. An evaluation of experimental procedures and the reporting of experimental errors, particularly for the cinematographic studies, is included. Consideration is also given to some of the more descriptive, coaching literature where points are raised which serve to highlight important biomechanical aspects of throwing technique. It is concluded that not enough relevant and reliable biomechanical data currently exist to answer many of the important questions about the technique of the discus throw, and some future research directions to help overcome this are recommended. PMID- 1433464 TI - The "twin peak" sign: reliable evidence of dichorionic twinning. AB - In twin pregnancies with a single placental zone, the presence of a triangular projection of placental tissue beyond the chorionic surface, extending between the layers of the intertwin membrane, has provided reliable evidence that there are two fused placentas (dichorionic, diamniotic) rather than a single shared placenta (monochorionic, diamniotic). This observation, dubbed the "twin peak" sign, was identified in 15 twin pregnancies, all proven to be dichorionic at birth, and in five triplet pregnancies, all proven to be trichorionic. This finding is produced by proliferating chorionic villi growing into the potential space between the two layers of chorion in the intertwin membrane. The single chorion of a monoplacental twin pregnancy serves as an intact barrier, preventing villi from growing between the two amniotic layers. A decision sequence incorporating the use of the twin peak sign is described for determining the type of twinning that has occurred. PMID- 1433465 TI - The variable appearances of fetal gallstones. AB - Only four cases of fetal gallstones have been reported previously, which implies that this condition is rare. Gallstones in children have been reported more frequently, and it may be that some of these are present in fetal life. Over a 12 month period in this department, seven cases of gallstones or sludge were seen within the fetal gallbladder. The variable appearances of fetal cholelithiasis are described and the possible causes discussed. Fetal gallstones may not be as rare as indicated by the paucity of cases in the literature. PMID- 1433466 TI - The choroid plexus pseudocyst: sonographic identification and characterization. AB - Amniocentesis has been advocated by some authors when fetal choroid plexus cysts are discovered, because of their reported association with karyotype abnormalities. We have noted an oval hypoechoic structure projecting into the adjacent choroid plexus, which simulates a cyst when imaged across its short axis, in 39 of 50 consecutive fetuses. This presumably normal structure or pseudocyst may represent the corpus striatum. Knowledge of its existence and benign nature will help avoid diagnostic errors and unnecessary amniocenteses. PMID- 1433467 TI - Sonographic diagnosis of infantile hypertrophic pyloric stenosis. AB - Twenty-five consecutive sonographic examinations performed at Flinders Medical Centre for possible infantile hypertrophic pyloric stenosis (IHPS) were analyzed retrospectively. The results and a pyloric muscle index calculated by a formula using length, diameter, muscle thickness, and body weight were compared with the clinical outcome (surgery or conservative management). In the children without IHPS, the calculated pyloric muscle index was less than 0.2, whereas in infants with proven pyloric stenosis, the index was greater than 0.2 (P < 0.001). This result suggested that the published index upper limit of > 0.4 to 0.46 was not valid in our institution. Pyloric length to muscle thickness ratio was also found to predict IHPS. A simplified index, including only length and muscle thickness, is proposed, whereby length (mm) plus 3.64 times thickness (mm), when greater than 25, implies IHPS. PMID- 1433468 TI - Postmenopausal tubo-ovarian abscess: sonographic considerations and clinical significance. PMID- 1433469 TI - Umbilical cord prolapse through a transverse uterine synechia. PMID- 1433470 TI - Ultrasonographic and color Doppler imaging of hemorrhagic epididymitis in Henoch Schonlein purpura. PMID- 1433471 TI - The value of Doppler flow analysis in the prenatal diagnosis of amniotic sheets. PMID- 1433472 TI - Color flow-guided repair of axillary artery pseudoaneurysm. PMID- 1433473 TI - Morantel tartrate release from a long-acting intraruminal device in cattle: pharmacokinetics and gastrointestinal distribution. AB - The pharmacokinetics and gastrointestinal distribution of morantel tartrate release from a sustained release trilaminate bolus in cattle were investigated over a 98-day period post-treatment. Six Holstein calves (125-150 kg) had permanent indwelling fistulae surgically inserted into the rumen, abomasum and terminal ileum. Samples of jugular blood, feces and ruminal, abomasal and ileal fluids were taken on days -3, 1, 4, 7, 10, 14 and weekly up to 98 days post-bolus administration. Morantel tartrate concentrations were measured by HPLC after extraction and clean-up. Morantel was not detected in plasma at any time after bolus administration. High concentrations of morantel tartrate were found in ruminal, abomasal and ileal fluids and feces over 98 days post-treatment. The morantel peak concentration (Cmax) was achieved at Day 1 post-administration in each of these compartments. The steady-state morantel concentration (Css) was achieved at approximately 10 days post-treatment and maintained for 91-98 days post-treatment in these gastrointestinal compartments. The morantel Cmax, Css, area under the zero (AUC) and first moment (AUMC) of the concentration-time curve were significantly higher (P less than 0.01) in feces than in other compartments. The in vivo drug release profile of this device has been determined. Steady-state concentrations for from 91 to 98 days have been confirmed. PMID- 1433474 TI - Rifampin disposition in the horse: effects of age and method of oral administration. AB - The effects of time and method of administration of rifampin with respect to feeding were evaluated in five mature horses. There was a significant (P less than or equal to 0.05) delay in time of maximum serum concentration and an apparent but not significant decrease in oral absorption when rifampin was given as a top dressing on grain as compared with administration in corn syrup 2 h before or 2 h after feeding. Although there were no differences between administration before or after feeding, administration 2 h prior to feeding was selected as the method of choice for future experiments. The effects of age on rifampin disposition were subsequently examined using this method of administration in six, 1-week old foals. Rifampin (10 mg/kg) was given at increasing age from 1 through 10 weeks and the pharmacokinetic disposition parameters compared. There were significant differences in the slope of the elimination phase (beta) and area under the curve (AUC) at 1 week through 6 weeks compared with 10 weeks or with values in the five mature horses. PMID- 1433475 TI - Pharmacokinetics and intramuscular bioavailability of amikacin in chickens following single and multiple dosing. AB - The pharmacokinetics of amikacin were studied in healthy mature female chickens (n = 6). Single doses of amikacin were injected as an i.v. bolus (10 mg/kg) and i.m. (20 mg/kg) into the same birds with a 30-day rest period between treatments. Amikacin was determined by the fluorescence polarization immunoassay method. The i.v. pharmacokinetics could be described by a two-compartment model with a t1/2 alpha of 0.150 +/- 0.064 h and a t1/2 beta of 1.44 +/- 0.34 h. The total body clearance was 0.109 +/- 0.017 1/h/kg and the volume of distribution at steady state was 0.193 +/- 0.060 l/kg. Following a single i.m. injection, the peak plasma concentration (Cmax) was 50.79 +/- 4.05 micrograms/ml and occurred at 0.50 +/- 0.26 h. The i.m. extent of absorption was 91.2 +/- 17.6%. Simultaneous modeling of i.v. and i.m. results provided estimates of an absorption half-life of 0.480 +/- 0.158 h. The i.m. pharmacokinetics after repeated administration were studied following the tenth dose (20 mg/kg, every 8 h). The Cssmax was 38.58 +/- 6.96 micrograms/ml and occurred at 0.79 +/- 0.37 h, and the biological half life of amikacin was 1.86 +/- 0.47 h. The multiple dosing yielded peak concentrations of 39 micrograms/ml and trough concentrations of 3.26 micrograms/ml. Based on these data, the recommended amikacin dosage in chickens is 20 mg/kg body weight every 8 h. PMID- 1433476 TI - Formulation and (bio)availability problems of drug formulations in birds. AB - Most drugs used for the treatment of birds are not formulated for birds. Therefore the availability of drugs for birds and their administration routes largely depend on formulations available for man, mammals and to some extent poultry. The problems with the application of existing formulations, the drug concentrations and the many different avian species are discussed. The desire of the avian veterinarian for the combination of several active compounds presents special problems. This again requires extra data on the interactions in galenic, pharmaceutic, pharmacokinetic and dynamic phases, which are generally not readily available. PMID- 1433478 TI - Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview. AB - The route of administration and formulation of the dosage form affect the bioavailability (rate and extent of absorption) of a drug and may thereby influence the intensity and duration of the pharmacological effect. Location of injection site may affect the plasma concentration profile of drugs administered as aqueous suspensions or sustained release parenteral preparations (procaine penicillin G). When absorption influences the rate of elimination ('flip-flop' phenomenon), the apparent half-life of the drug will be increased (cefazolin sodium, i.m.; meclofenamic acid, p.o.). Absorption generally approximates a first order process and either the absorption half-life or the mean absorption time (statistical moment term) will provide an estimate of the rate of absorption. The method of corresponding areas is the usual technique employed in estimating the extent of absorption (systemic availability). Inherent in this technique is the assumption that clearance of the drug remains unchanged. In horses, the time of feeding relative to oral dosing has been shown to affect systemic availability (rifampin, trimethoprim) and pattern of absorption (phenylbutazone). Oral paste formulations (trimethoprim-sulphadiazine, ivermectin) are convenient to administer, allow precision in dosage compared with powders or granules added to feed, and could provide sustained release. Assessment of bioequivalence is based on relative bioavailability, using a reference dosage form, together with a measure of the uncertainty (variance) of the estimate. Bioequivalence relies on the concept that preparations of a drug which provide essentially equivalent plasma concentration profiles should produce the same therapeutic effect. PMID- 1433477 TI - Bioavailability and bioinequivalence of drug formulations in small animals. AB - Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine. Although comparable bioavailability ('bioequivalence') is though to ensure comparable clinical effectiveness and safety ('therapeutic equivalence'), the relationship between bioinequivalence and therapeutic inequivalence is less clear. Thus the prevalence of clinically important differences in bioavailability is unknown. While similar concerns have arisen about drug products used in small animal practice, there have been few investigations and some earlier reports are incomplete. However, there are indications of bioinequivalence with enteral formulations of ampicillin, aspirin, chloramphenicol, digoxin, mitotane, oxytetracycline, penicillin V and theophylline. Other studies have suggested bioequivalence with enteral formulations of chloramphenicol, digoxin, phenytoin, oxytetracycline and thyroxine. Limited data for injectable preparations showed bioinequivalence with chloramphenicol and possibly oxytetracycline. There is no reason to expect formulation-related bioinequivalence to be less prevalent in veterinary than in human medicine. Indeed, it may be more common in veterinary practice because other potential influences on bioavailability (food, diseases, other drugs, etc.) are frequently ignored, and cheaper generic products are often favoured for economic reasons. PMID- 1433479 TI - Effect of inhalation anaesthetics on total respiratory resistance in conscious ponies. AB - Total respiratory resistance was measured rapidly and non-invasively in 6 conscious ponies before and after they inhaled approximately 25% of the minimal anaesthetic concentration (0.25 MAC) of either enflurane, halothane, or isoflurane, over a 10 min period. The forced random noise (FRN) method was used to measure the impedance over the frequency range of 5 to 40 Hz and its real part, the resistance, was extracted from these impedance measurements. At the concentrations used, halothane appeared to have no effect on the total respiratory resistance; enflurane and isoflurane seemed to increase it but the changes were not statistically significant. PMID- 1433480 TI - Prescribing of drugs for food-producing animals in Norway. Information about withdrawal times. AB - The prescribing of drugs for food-producing animals in Norway was investigated with special emphasis on written information given about withdrawal times. The study was designed as a cross-sectional prescription survey. Of 1518 prescriptions for food-producing animals, it was concluded that 1224 of the prescriptions were for drugs requiring withdrawal times for meat, milk or eggs. Of these 1224 prescriptions, 82.8% were for veterinary preparations, 6.6% were for human preparations and 10.6% were for other drugs. For 20.8% of the prescriptions, information about withdrawal time(s) was missing. For prescriptions for veterinary preparations this figure was 5.9%, and for prescriptions for human preparations and other drugs 95.1% and 90.8%, respectively. For veterinary preparations approved for the intended species, as many as 99.2% gave information about withdrawal times on the drug container label. Lack of information about withdrawal times might give rise to drug residues in food for human consumption and thus pose a potential hazard to human health. PMID- 1433481 TI - Effect of erythromycin on L-threonine transport in rabbit jejunum in vitro. AB - Several antibiotics characterized by different molecular structures are known to affect some intestinal activities. Some of them have been described as inhibitors of the intestinal sugar and amino acid transport with different mechanisms. Erythromycin (EM) is a macrolide antibiotic acting as a motilin agonist and thus stimulating the gastrointestinal motor activity. Since several substances which increase the motor activity of the gastrointestinal tract may produce effects on the intestinal absorption of nutrients, the present study has been carried out to determine whether erythromycin affects the L-threonine intestinal absorption. The results obtained indicate that erythromycin diminishes the L-threonine intestinal transport, probably at the mucosal border level. Two groups of experiments carried out, with Na(+)-deprived medium and ouabain-enriched medium, might indicate that erythromycin action could be due to either a direct or an indirect action on the Na(+)-dependent L-threonine transport located in the brush border.